Chapter 44: Vascular Conditions

CHAPTER 44 Vascular Conditions CONTENTS A. Aneurysms . . . . . . . . . . . . . . . . . . . . . . . . 1509 1. Summary . . . . . . . . . . . . . . . . . . . . . . . 1509 2. Extracranial Aneurysms . . . . . . . . . . . . . 1510 3. lntracranial Aneurysms . . . . . . . . . . . . . 1511 (a) Large Infraclinoid Internal Carotid Aneurysms . . . . . . . . . . . . . . . . . . . 1512 (b) Aneurysms within the Cavernous Sinus and Carotid-Cavernous Fistula . 1515 (c) Supraclinoid Aneurysms of the Anterior Part of the Circle of Willis .. 1520 (d) Aneurysms of the Internal Carotid-Posterior Communicating Bifurcation . . . . . . . . . . . . . . . . . . . 1520 (e) Mechanisms of Third Nerve Damage . 1521 (f) Aneurysms of the Vertebro-basilar Arterial Tree . . . . . . . . . . . . . . . . . . 1523 B. Other Vascular Malformations . . . . . . . . . . 1523 l. Arterio-venous Malformations . . . . . . . . . 1523 2. Anomalous Vessels . . . . . . . . . . . . . . . . 1524 C. lntracranial Aneurysms Versus Pupillotonia . 1525 D. Migraine Variants . . . . . . . . . . . . . . . . . . . 1526 1. Summary . . . . . . . . . . . . . . . . . . . . . . . 1526 2. "Ophthalmoplegic Migraine" . . . . . . . . . 1527 (a) Appearance . . . . . . . . . . . . . . . . . . . 1527 (b) Terminology . . . . . . . . . . . . . . . . . . 1531 The term "cerebrovascular disease' designates any abnormality of the brain resulting from a pathologic process implicating blood ve sels ... any lesion of the vessel wall, occlusion of the lumen by a thrombus or embolus, rupture of a ve sel, altered permeability of the ves el waJI and increased viscosity or other change in the quality of the blood. (Adams and Victor, 1977) About half of all eriou neurologic impairment is due to va cular condition . The different kinds of di ease vary in etiology, anatomic ite and pathologic mechanism (Table 44-1). As in the other chapter of this book, no general survey i attempted· and only tho e conditions that are of intere t from the point of view of pupilJary pathology are considered. (c) Mechanism, Location, and Clinical Significance . . . . . . . . . . . . . . . . . . (1) Location . . . . . . . . . . . . . . . . . . (2) Nature of the Lesion . . . . . . . . . (3) Clinical Significance . . . . . . . . . . E. Cerebrovascular Accidents . . . . . . . . . . . . . l. Summary . . . . . . . . . . . . . . . . . • . . . . . 2. Vascular Lesions of the Caudal Brainstem . . . . . . . . . . . . • • . • . . . . . . (a) "Central Homer's Syndrome" . . . . . . (b) Pontine Miosis . . . . . . . . . . . . . . . . 3. Vascular Lesions Affecting the Rostral Brainstem . . . . . . . . . . . . . . • . . . . . . . (a) The Diencephalic-Mesencephalic Border Zone . . . . . . . . . . . . . . . . . . (b) The Diencephalon and Cerebral Hemispheres . . . . . . . . . . . . . . . . . . 4. Occlusion of Cerebral or of Ocular Blood Supply by Remote Lesions . • . . . . . . . . . (a) "Posterior Cervical Sympathetic Deficit": The "Barre-Lieou Syndrome" . . . (b) Vertebro-basilar Insufficiency and Occlusion of Other Large Vessels ... F. Essential Hypertension . . . . . . . . . . . . . . . . 1532 1533 1533 1536 1537 1537 1538 1538 1539 1540 1540 1545 1546 1546 1548 1551 Aneurysms are considered first because pupillary signs may contribute to an early diagnosis and to differentiation of these potentially lethal condition from conditions that do not pose a threat to life. These include migraine variants, which can mimic aneurysms perfectly. In cerebrovascular accidents (both by hemorrhage or vascular occlusion) pupillary finding usually are only incidental and do not contribute greatly to the diagno is. For this rea on we have no elaborate description of these conditions even though they are by far the most common vascular cause of neurologic deficits. Patients with essential hypertension do not have distinctive pupillary signs, as has been claimed, so that the section dealing with hypertension is brief. A. Aneurysms By an aneurysm, then, I under tand the dilatation of the coats of an artery, arising probably from disease or accident, producing weakne , which becomes the remote cause, while the force of the circulation i the immediate cau e. (John Hunter, 1785-86) 1. Summary Aneury m of the aortic arch and carotid artery in the neck can cau e sympathetic paraly i . Thi ha been known since the early part of the last century. Later, however, it became apparent that some of the patients did not have a Homer's syndrome but had spastic miosis or an Argyll Robertson pupil instead. This occurrence with aortic aneurysm wa due to the fact that the patient. had syphilis, responsible for both the pupiJlary midbrain syndromes and aortitis. Intracranial aneurysms of the carotid artery and its branche or of the vertebro-basilar arterial tree, may 1509 1510 / V. Pupillary Pathology: Pupillary Signs in Various Diseases Table 44-1. Vascular conditions that may affect the pupil 1. ANEURYSMS AND VASCULAR MALFORMATIONS (1) Aortic or extracranial carotid aneurysms (2) Intracranial aneurysms of the carotid or basilar artery or their branches (3) Carotid-cavernous fistula (4) Arterio-venous malformations 2. CEREBRO-VASCULAR ACCIDENTS (1) Stenosis or thrombosis of cerebral vessels (2) Embolism (fragments of thrombi, especially due to heart disease or atheromatous plaques; infective; by tumor cells; traumatic, by air or fat emboli) (3) Hemorrhages (hypertensive; traumatic; secondary to blood diseases or tumors) - - 3. ARTERITIS (1) Infectious diseases (meningo-vascular syphilis; tuberculous, fungal, and bacterial meningitis ; other infections ) (2) Non-infectious ( connective tissue diseases; temporal arteritis) 4. THROMBO-PHLEBITIS Secondary to infectious diseases (ear, face, paranasal sinuses), with bacterial meningitis or subdural empyema 5. SYSTEMIC VASCULAR INSUFFICIENCY Cardiac arrest or trauma; occlusion of major arteries to the brain (aortic arch syndrome, vertebro-basilar insufficiency, "subclavian steal" syndrome, etc.); vascular hypotension due to dysautonomic conditions; Raynaud's disease * 6. MIGRAINE VARIANTS (1) Common, classic, and other forms (2) Cluster headache (3) Ophthalmoplegic migraine Traumatic, infectious, etc. vascular damage is described in the chapters dealing with these entities. * More often its treatment by upper thoracic sympathectomy or by sympatholytic drugs. involve the pupilloconstrictor fibers in the third nerve, the postganglionic pupillodilator fibers, or both, depending upon the location of the lesion. The pupillary signs are combined with (1) other oculomotor damage, (2) general neurologic impairment, and (3) headache. The headache of a leaking or ruptured aneurysm usually is nonlocalizing. Infraclinoid and basilar aneurysms can cause trigeminal pain and sensory deficit; and unruptured supraclinoid aneurysms usually bring about ipsilateral pain in and around the eye, forehead, and temple but no trigeminal nerve loss. Tumors (such as meningioma of the sphenoid ridge or tumors invading the cavernous sinus), trauma, and infections also can cause parasympathetic pupillary deficit. These conditions differ from aneurysm in their onset, course, and other features. In ophthalmoplegia due to aneurysms, sparing of the pupil is extremely rare. In contrast, the abnormal ocular and pupillary movements of the "third nerve misdirection syndrome" develop often after third nerve palsy due to aneurysm, except when early surgery has brought about rapid and complete recovery of the nerve. Patients with aneurysms may have repeated bouts of pain (with or without oculomotor palsy) due to expansion or leaking of the sac; and these aneurysms are occasionally mistaken for migraine or "ophthalmoplegic migraine." Inversely, the diagnosis of aneurysm is some- times considered in patients with tonic pupils because tonic pupils in the acute stage show all the features of internal ophthalmoplegia. For these patients the rule should prevail that parasympathetic impairment with pain is due to aneurysm until proven otherwise, and immediate workup is required. 2. Extracranial Aneurysms As mentioned in Chapter 25, such lesions first attracted the attention of clinicians to the sympathetic ocular nerve supply. Description of patients with sympathetic deficit due to aneurysms of the aorta or of the carotid artery predated not only Homer's report but also the work of Budge, Waller, and others who clarified the physiology of the sympathetic nervous system around the middle of the last century. As early as 1809 Cooperobserving signs of sympathetic impairment on one sidemade the diagnosis of internal carotid aneurysm in a living patient whom he treated successfully by ligating the artery below the defect. Numerous patients were subsequently seen by other authors. Usually the pupil on the side of the lesion was smaller than that on the other side; and there were partial ptosis and facial vasomotor and sudomotor defects (S in Table 44-2). However, this was not invariably true. Sometimes the pupil on the side of the lesion was the larger one; or both of them were 44. Vascular Conditions / Table 44-2. YEAR --1809 Extracranial aneurysms involving sympathetic pupillodilator fibers AUTHOR Cooper Coates Cooper Hope 1851 Wiilslie 1854 Gairdner 1855 Gairdner 1856 Banks 1856 Willshire 1857 Banks 1857 Cockle 1857 Williamson 1858 Ogle Walslie 1862 Gairdner 1862 Walshe 1863 Cockle 1866 Hutchinson 1869 Poiteau 1869 Eulenburg - - - &Guttman 1873 Eulenburg - - - & Guttman 1873 Walshe 187't Forster 1879 Stewart 1880 Powell 1884 M'obius 1885 Finla;):'.SOn 1886 Hale-With 1886 Pasternatsky 1895 Jackson 1900 Balmelle #19 #20 1900 " 1900 Harris 1901 Babinski 1901 Renon-Sollier 1902 Beauchesne 1902 Chaillous # 1 1902 #2 " T902 Joifroy 1902 Vasguez 1902 Wall & Walker 1821 1836 1839 mo 1511 ANEURYSM internal carotid at bifurcation carotid aneurysm same case :auto12sl'. aortic aneurysm tlioracic aneurysm subclavian aneultim aortic-carotid b,.......rcation aneurysm thoracic aortic aneurysm upper left chest aneu!:,YSID aortic aneurysm ascending: aortic aneur_}'.sm aortic, innominate aneurysms thoracic and abdominal aorta aortic aneurl'.sm aortic aneur;):'.sm common carotid aneur;):'.sm aneurysms carotid aneurl'.sm carotid aneurysm carotid aneurysm aortic arch aneurysm aortic aneurl'.sm aortic aneurysm thoracic aortic aneur;):'.Sm carotid aneurl'.sm aortic arch aneur;):'.Sm aortic aneurysm aortic aneurlsm thoracic aneurysm ascending aortic aneurysm abdominal aortic aneurysm aortic aneurysm aortic aneur;):'.Sm aortic aneurysm aortic aneur;):'.Sm thoracic aortic aneurysm aortic bifurcation aneurysm aortic aneurysm aortic aneur;):'.Sm thoracic aneurysm PUPIL s s s s YEAR AUTHOR Widal & Lemierre Babinski 1903 Boudinski 1903 S (nr) 1903 Lorrain & Verdier S(?) 1904 Conzen S,* 1904 Dufour 1904 Merklien & S{?) Pouliot s --1905 Hoch singer S(?) 1905 Krantz S(?) 1905 Reutsch S,* s * 1906 Crouzon Malfatti 1906 s 1906 Sentein S* 1907 Perier s 1907 Striimpell S,* S(?)* 1908 Cantonnet 1908 Nonne s 1910 Laignel - Lavas tine 1910 Osler 1911 Hirtz & Braun s 1912 Deneke s 1912 Winaver S* 1913 Babinski S* 1913 S* Merklien & Legros s 1914 Loeper & s Mongcot s s Nonne & s Wohlwill s T9I6 wrrae 1917 Noethe {?)* 1921 Dreyfus S* 1924 Bramwell * 1924 Markow s 1925 Lentz * 1931 Nonne * 1935 DeJong * 1953 Ehlers * 1968 Davis & al. * (?) 1976 Greiner 1976 West &al. 1902 s mr PUPIL ANEURYSM aortic aneurysm aortic aneurysm aortic aneurysm * --*-- s aortic disease aortic aneurysm S* ----.--S* carotid, aortic aneurysm aortic aneurysm aortic aneurysm aortic aneurysm aortic aneurysm substernal aortic aneurysm ascending aortic aneurysm aortic aneurysm aortic aneurism aortic aneurysm aortic aneur_}'.Sm aortic aneurysm thoracic aneu!]'.sm aortic aneurlsm aortic aneur_}'.Sm aortic aneurysm aortic aneurysm * _s__ * s * ---"'-'- S* ----.----*-* -s-* -s-- ~ -.- -r--*-- -.----- aortic aneurysm aortic aneurysm aortic aneurysm carotid aneu!:,YSID aortic aneurysm aortic aneurlsm aortic aneurysm aortic aneurism aortic aneurysm aortic aneurysm aortic aneurysm aortic aneurlsm subcranial aortic aneu!:Ysm carotid aneurysm carotid artery disease * * --* --.-s * * --*-* --*-- --s-s--s-s -s-- S = sympathetic deficit; *=syphilis, Argyll Robertson syndrome, or other signs of syphilitic pupillary impairment; (?) = author's diagnosis is questionable; numbers in brackets pertain to case numbers in original report. ADDITIONS 1957, Bonnet: carotid aneurysm; 1964 1 Obara &al.: carotid malformation; 1978 1 Fisher & al.: spontaneous dissection of cervico-cerebral vessels; 1980, O'Dwyer & al. : spontaneous dissection of carotid artery; 1986 1 Goldberg & al. : cervical carotid artery dissection; 1988, Thompson: dissecting aneurysm of the carotid artery . See also Tables 25 -1, 25 -5, 25 4 , and 25 -25. constricted, with feeble or absent reactions to light and without sympathetic ptosis, vasomotor, or sudomotor defects (asterisks in Table 44-2). Further, miotic, poorly reacting, or fixed pupils or Argyll Robertson pupils were also found in patients with aneurysms of the lower thoracic or abdominal aorta. These lesions could not possibly have interrupted the oculo-sympathetic nerves. Even diffuse aortitis without aneurysmal dilation was accompanied by the Argyll Robertson and related signs. In 1901, Babinski recognized that the pupillary defects were not due to pressure upon the sympathetic nerve by the vascular lesion at all. Instead, both the vascular and the pupillary impairment were brought about by a common cause: these patients had syphilitic aortitis, and the pupillary syndromes were also syphilitic in origin. * S,* aortic arch aneurysm Because syphilis so often was the cause of aortic aneurysms at that time, many physicians believed that intracranial aneurysms also were syphilitic in a high percentage of cases. And indeed, syphilis was so prevalent before effective treatment became available that patients with intracranial aneurysms quite often had syphilis. However, it became clear with time that aneurysms of cerebral vessels rarely were caused by this disease. 3. Intracranial Aneurysms The aneurysms that concern pupillary pathology especially are those which involve the intracranial vessels. Among these the most common are "saccular" or 1512 / V. Pupillary Pathology: Pupillary Signs in Various Diseases Table 44-3. Major types of cerebrovascular diseases and their frequency TYPE OF DISEASE Atherosclerotic thrombosis Lacunes Embolism Hypertensive hemorrhage Ruptured aneurysm and vascular malformations Indeterminate Other** HARV ARD STROKE SERIES ( 756 successive cases * ) 244 129 244 84 {33%} (18%} ( 33%} ( 11%) 55 ( 7%) BCH AUTOPSY SERIES ( 1 79 cases +) 21 ( 12% } 34 (18.5%} 57(32 %} 28{15.5 %} 8 ( 4.5% ) 17 ( 9.5%} 14 ( 8% ) From Adams & Victor, 1977, Table 28-2. * Compiled by Drs J. Mohr, L. Kaplan, D.Pessin, P. Kistler, and G,Duncan at Massachusetts General Hospital and Beth Israel Hospital (Boston). + Compiled by C.M. Fisher and R.D. Adams in an examination of 780 brains during the year 1949 at Mallory Institute of Pathology, Boston City Hospital. ** Hypertensive encephalopathy, cerebral vein thrombosis, meningovascular syphilis, polyarteritis nodosa. "berry" aneury ms. They are sacs, usually roundish or oval in shape and of variable size. Others are "fusiform," that is, spindle- haped enlargements, sometimes called " arteriosclerotic aneurysms." The chief cause of aneurysms is congenital absence of the media in sections of the vessel walls. As the patient grows older, the weakened portions of the ves el walls gradually balloon out in response to intravascular pressure exerted upon them. Arteriosclerosis and systemic hypertension exacerbate the development. In some cases trauma, infections, or connective tissue disease contribute to the pathologic process. Compared in numbers to occlusive strokes, aneurysms are not common causes of cerebral vascular impairment (Table 44-3). But they often lead to rapid death· and many of these treacherous lesions can be treated surgically when they are discovered in time. Early objective signs are therefore important. The pupiUary and other ocular signs of intracranial aneurysms were well known during the early part of the la t century. But with rare exceptions the lesions were discovered only at autopsy (or by the surgeon searching for something else) until 1923, when Symonds clearly delineated the criteria that allowed the diagnosis to be made in life. And with development of intracranial angiography (Moniz, 1933) it became possible actually to show these lesions in the living patient. Many important contributions about this subject have been published over the years. The ones reviewed in connection with pupillary involvement are listed in Table 44-4. This list is quite fragmentary. The classic pupillary sign in patients with intracranial aneurysms is an enlarged, poorly reacting, or fixed pupil as part of a third nerve palsy. In almost half of the cases this is the sole motor defect (Figure 44-1 ). In additional cases the third nerve is damaged together with other oculomotor nerves and the fifth nerve. [n yet others the motor system of the eye remains intact, but vision is l impaired; or the sympathetic oculo-pupillary fibers are interrupted, with or without objective signs of fifth nerve deficit. These different findings are not difficult to understand when the anatomic relation between the arteries and nerves at the cranial base are kept in mind. In the following summary the effects of internal carotid aneurysms are considered first, in the order of their location along the artery from its entry into the carotid canal to its supraclinoid branches. Pupillary and other signs caused by aneurysms of the vertebra-basilar arterial tree are described second (sec summary in Table 44-5). (a) Large Infraclinoid Internal Carotid Aneurysms As the carotid artery enters the base of the skull by way of the bony carotid canal, it is accompanied by the postganglionic sympathetic fibers to the eye and forehead. Aneurysms located below or within the carotid canal may therefore injure this neuron. The resulting combination of ipsilateral head pain and postganglionic Homer's syndrome is sometimes called " Raeder' syndrome." This is, however, appropriate only when the aneurysm extends beyond the carotid canal, damaging the trigcminal nerve and the sympathetic fibers where they run close to the Gasserian ganglion within the ophthalmic branch of the fifth nerve (see also Chapter 25). Large infraclinoid aneurysms have been found to do this. They also can erode the petrous portion of the temporal bone, the clinoid process and sellar floor, or the optic foramen and superior orbital fi ssure. They may expand into the underlying sphenoid sinus or into the orbit. They also can bulge upward, lifting the dura to fill the middle fossa, or even bursting through the dura (along the artery) to project into the brain. Such huge sacs may push the temporal lobe aside and (rarely) shift the entire brain toward the opposite side (Dandy, 1944; cases 8 and 9 of his Table A; see Table 44-6, first part). They may bring about endocrine signs by destruction of 44. Vascular Conditions / Table 44-4. YEAB 1846 1849 1865 1866 1872 1876 1878 1884 1884 1885 1887 1889 1897 1897 1898 1898 1904 1910 1910 1916 1918 1923 1923 1924 1924 1926 1928 1928 1929 1929 1931 1932 1932 1933 1933 1934 1934 1936 1937 1938 1938 1938 1939 1939 1939 1939 1940 1941 194 1 1942 1944 1946 1946 1948 1948 1948 1949 1513 lntracranial aneurysms involving pupilloconstrictor fibers running with the tbi rd nerve AUTHOR !CONDITION 3rd nerve palsy due to "sanguinous effusion of circumscribed vascular enlargement" 3rd nerve Qalsy due to aneurvsm I cit. Jeffers on) • th 1 ) left dilated sluir!!'ish ouoil, R hemiolegia: aneurysm o~ middle cerebral artery (cit. Bar O ow 29 internal carotid· 11 vertebro - basilar. 3 miarue meni=eal aneurvsms lcit.Bartliolow) 1 case basilar arte'r y aneurysm with 3rd, 5th & 6th_nerve damage: pupil fixed but not very large; discussion of literature on carotid, vertebro basilar and other aneurJ!:sms 3rd nerve ,ealsy due to intracranial aneu!:Ysm (cit . Jeff~rson ) . Peacock g.,17: 3rd nerve palsy due to pea sized aneurysm of R 1:13ternal c'.11'otid . Bull (1) 21: Horner's with 5th nerve deficit due to (probably) mtracranial carotid aneurysm Nieden (1) ~ 9: 3rd nerve palsy with repeated seizures , (probably ) a ue to aneurysm Schafer (1) rd nerve pals:i:-: wiili misairection ana liemiplegia: pro6a6Iy aneu rysm Jesso,e(l) ~ 22: cherry sized carotid an_eu~sm ( rupturea ) , cau~ing 3ra ?erve palsy ana aeaili F iedler (1 ) . We ir-MitclieH QJ aneurysm oi anterior commumcat10g artery iliat cut cfoasm s~1tt:3:1If Char cot (1) I\ case labelled "oohthalmoplegic mill:raine" : 3rd nerve palsy with mis -irecbon, probably aneur. D'Astros (1) A_ ~ 69 : 3rd nerve pals;)'., ,erobabl;)'. aneu!}'.S~ , called '.'o,ehthalmo,elegic migraine 21: bouts of supraorbital pain, proptoslS and orbital edema and hemorrhages, said to be due Brasch & Levinsohn (1) to "migraine" . . . ~ 33: 3rd nerve palsy with cerebral signs _ . 3rd nerve misdirection; ,erobablJ!: aneurysm v. Solder (1) rd nerve ,ealsr with misdirection on recove1:.y, 2robabl_y d_ue to aneur_ys~ Hermann 111 ~ 40: total isolated 3rd nerve 2alsy ~ died of ru12tured mternal carotid aneu!}'.Sm Beykows ky (l} 36 : 3rd ne rve ,ealsr due to ruptured internal carotid aneurysm Pascheff (1) large ,ea,eer on 3rd nerve ,ealsy vs . intracranial aneu!:Ysm ( cit . Jellerson l F e arns ides rupture d large posterior communicating artery aneu rysm Brouwer (1) 3ra nerve ,erusr with oecreasea 5ili nerve sensation ana fronto -occip ital pain suggest aneurysm Cusliing (g) 3rd nerve 2alsr and other signs due to intracranial aneu rysm Si monds (5) carotid---{)avernous aneurysms: 38 own cases and statistics from literature Locke (588) 3rd nerve palsy aue to intracranlal aneurysms, especiall,l:'. of carotio aaa its 6ranclies Paton (2) intracranial aneurysms ( case histories and statistics) Conway (43) Nattrass aneurysms causing 3rd nerve 2alsr 3rd nerve Qals;y due to aneurysm (cit . Jefferson) Szekely 3rd nerve palsy due to aneurism of carotid ( at branches of circle of Willis) Albr!ght Br ock (1) _ _ internal carotid aneurvsm (or carotid---{)avernous fistula \ : ouoils poorly reactive, proptosis &bruit 3rd ne rve palsy and pain due to aneurysm of post. comm . artery: thought to be syphuitic Dassen • Cr itchley (l} A ~ 37 : 12 ;year history of 11 migraine 11 ana 6Ieeaing aneurysm Dott (m) _ 3rd ne rve palsy due to intracranial carotio aneurysms (cit.Jellerson) Bramwell (s) ~ cases described as "oohthalmoolegic migraine" often have a bleecling aneurysm (case Iiistories) intracranial arterio-venous aneurysm: 1 case (traumatic) and reference to 621 in the Heard & Abrams on {l) _ literature Bramwell (3). 3rd nerve ~alsi due to leaking aneurysm; some called "02hthalmopl egic migraine" 3rd nerve ealsi due to intracranial aneurisms ( cit. Jefferson) Garver unruptured intracranial aneurysms causing defects of 3rd,4th,5th &6th nerves, perhaps via MacKinney embarrassment of their blood supply 12 patients with intracranial aneurysm (01 53) had damage to optic nerve, cliiasm or tract Jeffers on (53) Ca ir ns signs and oiagnosis of intracranial aneurysms saccular aneurisms of internal carotid in cavernous sinus : pain ana opfitlialmoplegia Jeffer s on (55) bleeding aneurisms at base : signs describea, including oculomotor aefects Luft (25A) most patients with spontaneous subarachnoid hemorrhage have bleeding aneurysms; pupils Hansen & are s l uggish or fixed on one or both sides, usuall;)'. large bu t sometimes small Staa (33) 3rd nerve and other cranial nerve palsies due to subarachnoid hemorrhages due to aneurysms Hess 30 page paper on intracranial aneurysms ( not reaa 1978) McDonald & Korb (m ) intracavernous c arotid aneurysm, causing pain, p roptosis and op hthalmoplegia Rub ino & ~uarti (1) cerebral hemorrhage from ruptured congenital aneurysm in a child: pupils were "moderately He rmann & MacGregor QL dilated and equal " Blirki (8) ~ - among 8 cases 01 11oothalmoplegic migraine'' 4 hao aneurysms: callee 11symptomatologic 11 arterio-venous c arotid aneurvsm: bruit, orootosis, mvdriasis, nnnr EOM , vascular siuns: Winther (1) Walsli & King:(32) 3rd nerve Qals;y with misdirection, due to aneur_ysms book on intracranial aneurisms ( large bibliogra,eh;\'.) Dandr (108) isolated 3rd nerve palsr among 158 cases with intracranial aneurysms Jefferson (55) Sunderland & path for pupillo---{)onstrictor fibers in 3rd nerve of man Hughes (4A) 22 patients of 75 with intracranial aneurvsms had eye sims : 21 had 3rd nerve deficit Cox (d . Walsh) Sunoerlano (210) autopsies ot arteries at the base in man, including relation of vessels to 3rd nerve Walsh (s ) ocular si1ms of saccular aneurysms : found pupils spared once, mecholyl + two times Alpers & of 60 case s with verilied aneurysm 2 had normal arteriograms: #1 hao intermittent headaches Ryan (2) for two years ; #2 had no pain France Gull Wood (l} Durand (43} Bartholow (120) A • Numbers in brackets denote numbers of patients in report; numbers without brackets are years of patient's ages; A = autopsies; d = spoke in discussion ; g = gene ral statement; #= case number; -+ = followed by; EOM = extraocular movements; (s) = s everal; (m) = many; . = patients with "migraine" history . 1514 / V. Pupillary Pathology: Pupillary Signs in Various Diseases Table 44-4 YEAR 1949 (continued) AUTHOR • Alpers & Schlezinger {7) --1950 Jaeger (31) . 1950 Le_y (1) 1950 Walsh (d. Jaeger ;g) 1952 Hamb,¥: (93 ?) 1952 Levin (1) 1953 Bonnet & Bonnet (1) 1953 Hamby (53) 1953 Harrison & Luttrell (3) --1953 Jefferson (29) 1953 Paul'igue & al (1) 1953 Matlow & Al:Qers (5) 1954 Dany & Lobstein (1) --1954 Hyland & Barnett (39) --1955 Henderson (119) 1955 Ver Brugghen {l) A 1956 Bozzoli (1) 1956 Rucker & al 1957 Bonnet & Bonnet (2) 1957 Bonnet (1) 1957 Lincoff & Cogan 195 TroupE & al (16) 1959 Meadows (15) 1960 Donahue (1) 1960 Duma &:i.l {l) 1960 Keefe & al (2) 1960 Money & Vanderfield (6) - -1960 Morello & Cucco (1) 1961 Reinecke {l) 1962 Bottrell & al (35) 1962 Madonick & Ruskin {l) 1963 Bodechtel 1963 Cogan & Moun~ 60) • CONDITION aneurysms of posterior communicating artery, with 3rd nerve palsy; #7 had bouts of pain with nausea and vomiting for many years, thought to be migraine 3rd nerve_oalsv du~ to internal carotid aneurysms ( some with migraine like pain ) compresswn of optic nerve due to aneurysm of carotid artery after 3rd nerve damage due to aneurysm, recovery is slow and mLsdirectwn frequent, indLcating pressure alone is not likely to be responsible for the damage 564 page book on intracranial aneur;i:sms; statistics oI own and ol I:152 cases Irom tfie literature ?1stologic stud,¥: of 3rd nerve rcgeneeation with miscirection, after aneurysm intra-cavernous carotid aneurysm with palsy of the 3rd, 6th and 5th nerves and proptosis; eatient had had migraine - like attacks with transient diplopia for three years spontaneous subarachnoid hemorrhages: 22 aneurysms, 1 arterio venous malformation cases with carotid -basilar anastomosis intra-cavernous conditions, including 29 saccular aneurysms, 17 traumatic carotid-cavernous f. ~ 20: pea - sized aneurysm at level of post. clinoid; improved on carotid ligation aneurysms of posterior communicating artery : all had 3rd nerve involvement ~ 48 with isolated iridoplegia due to juxta-clinoid carotid aneurysm cases with cranial nerve involvement among 94 patients with intracranial aneurysms; discussion of mechanism of motor deficit intracranial aneur,Ysms: 5 were missed in arteriogra.m { 4 deaths, 1 blind, 1 hemiplegic ) child with 4 normal arteriograms and migraine-like ophthalmoplegic attacks: aneurysm suspected died of subarachnoid hematoma secondary to ruptured aneurysm of Sylvian arte1:y among 653 cases with eye muscle defects, aneurysms were most common cause of 3rd nerve palsy oculomotor palsy due to aneurysm ( not verified anatomically) sympathetic deficit due to small carotid aneurysm in middle fossa 3 patients with diabetes, 3 with tumor, 1 with leukemia, 2 ophthalmoplegic migraine to show that 3rd nerve palsy plus pain do not always prove aneurysm among 134 patients with aneurysm had ophthalmoplegia ( 8 case reports ) internal carotid aneurysms ( unruptured ) , followed for several years; all except 3 with 3rd nerve ancur_ysm in case with migrainoid headache 53 with Horner's, "ophthalmic mig2,aine" and 6th nerve paresis due to anomalous int. carotid 5 and #6: ruptured aneurysms with 3rd nerve damage 6 patients with aneurysm, 3 with angiomatous malformations, had periodic Fieadaches and 3rd nerve defects • C j •• ~- • - -1963 1963 1963 1964 1964 1965 1965 1966 1966 1967 1968 1969 - -196:1 1970 1972 1974 spontaneous carotid-caver-nous fistula with proptosis and 3rd nerve defects ~ 45 with classical miirrainc his torv and vascular malformation oculomotor palsy with supraclinoid carotid artery aneurysms ( 25 bleeaing ) ~ 60 with carotid - basilar anastomosis and 3rd nerve defect textbook; p.314 on carotid and other aneurysms, with oculomotor defects ophthalmoplegia due to intracranial aneurysms: (1) infraclinoid; (2) saccular at carotid b ifurcation; (3) vertebra-basilar ( saccular or fusiform) 3rd nerve damage due to aneurysms ( and other causes ) ~ 59 with bilateral ophthalmoEleg:ia due to large carotid ancur;)'.sm filling the sella Green & al Hancock (1) Johnston & 3rd nerve palsy due to aneurysm with incomplete recovery: 2 had aberrant regeneration Pratt Johnston (11 ) eye signs with intracranial aneurysms (statistics) : 3rd nerve most often involved Daley & al (65) 3rd nerve palsy, 38 due to intracranial aneurysms Green & al (130) ~ 54 with frontal & eye pain and ips ilateral isolated 3rd nerve palsy due to aneurysm at Oshima (1) carotid posterior communicating bifurcation intra cavernous carotid surgery Parkinson Blend! & Bull (18jA° patients withmigraine - like history &ophthalmoplegic episodes due to vascular malformation survivors of internal carotid aneurysm with 3rd nerve palsy ( 15 bleeding); pupils were Hepler & involved in all; otos is was absent in 13, partial to full in 12 Cantu (25) intracranial supra-cavernous carotid aneurysm causing Raeder's synctrome: sympatnetic Law & deficit, with compress ion or focal spasm of adjoining cax·otid artery Nelson (1) Payne & ~ 35 with aneurysm of carotid-posterior comm. junction and internal ophthalmoplegia Adamkiewicz (1) p . 397: unruptured aneurysm of int. carotid and post. comm. junction, with 3rd nerve palsy Walsh & Hoyt Garcin & • recurrent palsies due to aneurysm, including 3rd nerve Manigaud {g) unilateral mydriasis and headache is often due to intracranial aneurysm Jagerman (g) internal carotid aneurysm at or near junction of post. communicating artery: recovery of Grayson & al (26) 3rd nerve depends on duration of palsy before surgery NOTE: Hutchinson usually is credited as having given the first account of this condition . His patient's aneurysm of the intracranial carotid artery was described in 1875 . It had been diagnosed correctly in life, eleven years earlier . The patient had survived without treatment. 44. Vascular Conditions Table 44-4 - YEAR AUTHOR Soni Kasoff & Kelly 1978 Trobe & al 1979 1980 1981 1982 1983 --1983 1986 1515 (continued) 1974 1975 -1979 -- / Felder & Camp Rom:fu-Campos &Edwards Fische r Smith & al . Gale & Crockard Kissel & al . O'Connor &a l . Oono CONDITION ane!!!J::sm of the EQSterior communicating arteri and oculomotor E!aral,rs_is {_n. r. ) . patient with an aneurysm of the posterior communicating artery at carotid bifurcation had OEhthalmoplegia with the EuE!il SEared . . . . . in patients with cavernous sinus aneurysm, the pupils may be spared if the mfer10r d1v1s1on of the 3rd nerve is spared; patients showed "misdirection syndrome"• or oculomotor plus Horner's svndromes a patient with intracranial carotid aneurysm that involved only the superior branch of the third nerve had the puEil spared aneurysm causing painful ophthalmoplegia but left the pupil spared 5 cases of 17 with oval pupils had ruptured saccular aneurysms patient with internal carotid aneurysm, arising distal from the origin of the ophthalmic artery, had 2u2il s2aring 3rd nerve E!aisr patient whose basilar aneurysm had bled into the third ventricle had an isolated large and fixed 2u2il during the first hour among 84 patients with aneurysms near the internal carotid - posterior communicating junction, 7 had the pupil spared at first, but in 4 pupil deficit developed within 5 days, and in 1 after 4 months described aneurisms causing EUpil-sparing third nerve palsy 9 50 1 with internal carotid aneurysm and pupil sparing ociilomotor palsy See also Chap ter ;:;: • the pituitary gland; hearing loss by damage to the inner ear via the petrous bone; blindness or field defects by pressure on the optic nerve, chiasm, or tract; pulsating exophthalmos by extension into the orbit; and neurologic signs by upward pressure or by invasion of the cranial vault. (b) Aneurysms within the Cavernous Sinus and Carotid-Cavernous Fistula Most infraclinoid aneurysms are smaller than this and arise from the carotid artery within the cavernous sinus filling part or all of it. The dural wall of the sinus gives mechanical support to the sac, so that rupture occurs less often than in other locations; and when it does happen a carotid-cavernous fistula results rather than a fatal subarachnoid hemorrhage. Unless the aneurysm extends beyond the cavernous sinus vision remains intact; and when it is damaged, thi occurs later, due to econdary vascular defects. Partial A ISOLATED CRANIAL N. 42% R(29) L (38) Figure 44-1. Ocular defects among ixty-five patients with intracranial aneul) ms who were fir t een by an eye eivice (Wills Eye Ho pital, Philadelphia). The location of the aneury ms i. shown in A, and the relative frequency of eye ign in 8. (From E.J. Dailey. J.A. Holloway, R.E. Murto, and .S. Schlezinger,Arch. Ophthal., Chicago, 71 (1964):463; 1964, American Medical A ociation) 1516 / V. Pupillary Pathology: Pupillary Signs in Various Diseases Table 44-5. Intracranial aneurysms that may affect the pupil LOCATION OCULAR AND OTHER SIGNS SUBCRA IAL or INTRA-PE TROUS head pain and ipsilateral postganglionic sympathetic loss INF RAC LINO ID (intracavernous) carotid aneurysm ipsilateral pain with paresthesias and sensory deficit in the territory of the 5th nerve; oculomotor paresis or palsy (N3, 4 & 6); postganglionic sympathetic deficit; usually no visual loss or signs of intracranial hemorrhage; PUPIL: not necessarily large, but all reflexes impaired (parasympathetic and sympathetic) CAROTIDCAVERNOUS FISTULA same as intracavernous aneurysm, with added proptosis, bruit, orbital edema, venous stasis and arterialization of veins in and around eye and forehead; may develop secondary glaucoma, visual impairment, exposure keratitis U) Q) .Cl t) 1a1-1 .D ~ a:! t ---------- -------------------------pain* without 5th nerve deficit; sometimes involvement of the ... SUPRACLINOID ~ "' 0... "' '.9 t) ...; .5 Q) £ bl) C 0 ...... "' U) 6 U) t::, Q) C "' internal carotidanterior cerebral or ophthalmic or ant. communicating junc tion aneurysms optic nerve, chiasm or tract: blindness or field defects, especially inferior temporal or hemianopic; enlarged optic foramen with ophthalmic aneurysms; neurologic impairment (anosmia, frontal lobe), and signs of subarachnoid hemorrhagc; PUPIL: sometimes afferent defect to match visual loss; rarely 3rd nerve involvement ------------------------------------SUPRACLINOID pain* without 5th nerve deficit; rarelyvisual field loss, 3rd internal carotidmiddle cerebral aneurysms ---------SUPRACLINOID internal carotidpost. communicating aneurysms BASILAR, POST.CEREBRAL-SUPERIOR CEREBELLAR-VERTEBRAL SYSTEM aneurysms or 6th nerve paresis; crossed hemiplegia & other neurologic impairment and signs of subarachnoid hemorrhage; PUPIL: rarely afferent or efferent disturbance of light reflex _ _ _ pain* without 5th nerve deficit; isolated (usually complete) 3rd nerve palsy; neurological impairment and signs of subarachnoid hemorrhage; PUPIL: classically large and sluggish or fixed, becoming smaller with time; upon recovery, signs of 3rd nerve "misdirection dyskinesia" fronto-occipital headache*, or trigeminal pain if 5th nerve is trapped; sometimes paresis of 3rd and 6th or 7th nerve on one or both sides; gaze palsies, internuclear palsies or other brain stem signs or hydrocephalus; signs of subarachnoid hemorrhage; PUPIL: uni- or bilateral parasympathetic deficit; pupil not involved in (cortical) visual loss, if present; dissociated pupils; afferent loss if optic tract is involved * For location and kind of pain, see text. or complete external and internal ophthalmoplegia (including the third, fourth, and sixth nerves) is an outstanding sign (see Figure 44-2 for anatomic relations). As part of this defect, the pupil usually reacts poorly or not at all to light and to near vision. However, it is often smaller than one would expect, in view of the disturbed light reflexes. This is due in some cases to added paralysis of the sympathetic pupillodilator fibers that accompany the fifth nerve. If the pupi\lary reflexes to light and to psychosensory stimulation are not tested carefully, this double deficit-sympathetic and parasympathetic-may not be recognized, and the absence of mydriasis interpreted as " pupillary sparing." 1 We have seen a number of such cases (see Figures 16 and 17 in Chapter 22). The hydroxyamphetamine test will reveal postganglionic sympathetic damage in such cases. Complete pupillary sparing is rare in cases with aneurysms in the cavernous sinus. But occasionallyespecially in the early stages, or when the superior but not the inferior third nerve branch is involved-the light reflexes are relatively well preserved in patients with l. The pupil may also become smaller when regeneration o( the third nerve occurs, with misdirection. evident third nerve damage. This contrasts sharply with the effects of supraclinoid aneurysms, especially those located at the junction between the internal carotid and the posterior communicating arteries: patients with aneurysms at this site usually have paralysis of the pupillary sphincter if the third nerve is at all involved; further, an enlarged, poorly contracting or fixed pupil is often the first and sometimes the only sign of third nerve damage due to supraclinoid aneurysms (Figure 44-3). Sunderland and Hughes's anatomic studies (1946) explained why this is so. Between the brainstem and about the middle of the cavernous sinus the pupil fibers in the third nerve are concentrated in a bundle. Where the nerve passes through the dura of the cavernous sinus-in close proximity to the internal carotid-posterior communicating bifurcation-the pupil fibers travel along the superior-medial surface of the nerve and are, therefore, especially vulnerable to injury by pressure from above, or by bleeding and subsequent connective tissue proliferation and adhesion to an aneurysmal sac. Kerr and Holloway (1964) followed the pupillary fibers in dogs, monkeys, and human brains and found them superficially in the third nerve, forming a loose spiral from superiorly 1 44. Vascular Cond it io ns Table 44-6. 1517 / Pain and ocular signs in patients with intracranial aneurysms FROM TABLE A: ANEURYSMS OF INTERNAL CAROTID ARTERY IN CAVERNOUS SINUS if -1 SITE OF ANEURYSM bilat. in CS, protruding upward into brain CS with intracranial extension CS with intracranial extension 4 CS with intracranial extension 5 L CS calcified _L R int. carotid , bulging from carotid canal L int. carotid, ruptured in CS 7 s huge sac from carolid canal, filling R middle fossa huge sac from carotid canal, filling middle fossa 9 10 small caruncle projecting from L CS 11 in midline above sella, attached to L carotid 2 3 -- PAIN oculom . severe frontal L fronto-parietal frontal I faci al & R eye, severe L frontal & parestbesia L frontal behind eye severe R frontal severe frontal R face and heao forehead hyper-&paresthesia L eye in attacks frontal & both eyes L3,4,6 L3 R3 L3 L3,4,6 R3 , 4,6 L 3 , 4,6 R 3,4 1 5 1 6 3,6 3 6L 0 H -+V -- -- -- - ---- ---- --R -- ---- -B -- 1st signs 4.5 y 3m ....,. 5w 4m Sm 22y 3m 16y ily --... iI .5m 4y 2y 3.5m FROM TABLE B· I TERNAL CAROTID ANEURYSMS ii SITE OF ANEURYSM PAIN oculom. 1 fusiform R int. carotid at entrance to vault none "migrainous" in spells none slight pain L eye none 0 0 0 0 0 0 R3 L3 L3 R3 R3 L3 -2- R internal carotid 3 T 5 6 7 8 9 10 ll 12 13 14 _]Q_ ~ 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 bilat.fusiform entire length of carotids fusiform L int.carotid at entry to vault (1) bilat . diffuse carotid; (2) basilar bilat. dilation of both int . carotids ( and tumor) saccular R int. carotid below post. communicating saccular L int . carotid below branches L internal carotid trunk saccular from int. carotid , 1/2 cm intracranially R R int. carotid trunk L internal cnrotid R int. carotid at entrance into cranium L int. carotid at entrance into cranium L int. carotid at entrance into cranium L int. carotid at 02st. communicating junction R int. carotid at post. communicating junction Lint. carotid at post. communicating junction R int. carotid at post . cerebral (anomalous) junction R int. carotid-post. communicating junction R int. carotid-post . cerebral (anomalous) junction (1) R int . carotid -post. communicating junction; (2) L int. carotid -ant. choroidal R int. carotid -post. communicating; (2) ant.cerebral 3 small, unruptured aneurysms: int . carotid, middle cerebral basilar Lint. carotid -post. cerebral (anomalous) junction fusiform dilation R choroidal (anomalous vessel) R int. carotid-post. communicating junction R int. carotid - post. communicating junction (1) Rant. choroidal, ruptured; (2) R int. carotid at post. communicating junction; (3) ant. commun ic. (1) large L int. carotid -post . communicating junction (2) anterior communicating (1) L and (2) small R int. carotid near 1st branch R {small) on int. carotid near post. communicating R int. carotid -post. communicating junction R int. carotid - ant . choroidal junction R int. carotid 3 mm above post. communicating (1) bilateral int .. carotid at post . communicating (2) ant. communicating L int. carotid between 2ost. comm. & middle cerebr. L int. carotid -middle cerebral junction L int . carotid -post. communicating junction R frontal & eye L temporal & behind eye head, non-localized R frontal -+ occipital occipital in attacks , R > L R frontal severe - - L eye and temple, not severe severe fronto-occipital L L supraorbital _ . ~eneral R frontal and orbital L occipital ___. frontal R frontal --...Eil'rontal back of neck - . frontal severe occipital L3 L 3,4 L3 R3 L3 R3 R3 0 no history - "terrific" head pain 0 none - severe severe severe severe occipital, 2 attacks R head and eye R head and eye R headaches severe beadaches 0 R3 R3 0 0 - - L eye and forehead none intermittent R temflle severe headache 4d none L3 none coma none generalized fronto-occipital 0 R3 0 R3 V -- +- - ~ + + + - H 1st signs 0 + 0 0 0 0 4y 5y 3m 5m Sm ? 0 6d 5w 0 - -- ~ 5m -- + 3w - - - - - + 4y ...... 4m 5m - . 3m --- ?+ acute (death) -+-- _Q__ lv 6y - . 7m + + """+ 2m -+- + 2m 2y ...... 3m + 0 -O* 4,¥: - +2d + - - - -+ 5w -- - + --+ -- - - 0 - + -+- """+ -+ --- -+- - - acute (death) 24 h necropsy 20d 3m ...... 80 2w 6d + 5m ~ 0 necropsy 0 necropsy + + + 6h Im _. 2d 2.5 m -- lOd -6w ~ 3w - -- 0+ necropsy - "+ 7m - -- "+ - - - -- ~a + acute (death) --- 0 - 0 0 0 - ---+ - - From Dandy's series, 1944, Tables A-G. #= Dandy's case numbers; oculom . = oculomotor loss; V = visual loss; H = cerebral hemorrhage; 1st signs = duration of signs in hours , days, weeks, months or years; 0 = absent; + = present; - = not mentioned (presumably absen-0; * = case ltl9 bled from occipital arterio - venous malformation, not from arterial aneurysm . 3 , 4, 6 = third, 4th, or 6th nerve on R or L . 1518 I V. Pupillary Pathology: Pupillary Signs in Various Diseases Table 44-6 (continued) FROM TABLE C: ANTERIOR CEREBRAL AND ANTERIOR COMMUNICATING ANEURYSMS ii LOCATION OF ANEURYSM PAIN oculom. 1 L anterior cerebral frontal 0 2 (1) ant. cerebral just beyond int. carotid, ruptured; general 0 (2) 3 unruEtured aneur.}':sms L middle cerebral 3 anterior communicating severe, generalized R3, lld 4 R anterior cerebral severe, R temple 5 L anterior cerebral severe occipital and backache diplopia 6 anterior communicating severe, base of brain 0 7 anterior communicating general for 1 year 0 8 R anterior cerebral sudden coma 0 9 L ant . cerebral & ant. communicating severe R head and neck 0 .1..Q_ L anterior cerebral frontal, occiEital and vertex 0 11 R ant. cerebral - ant. communicating junction headache 12 L anterior cerebral-ant. communicating junction frontal and in eyes diplopia 13 L anterior communicating none 0 14 ant. cerebral -ant. communicating junction generalized head &back of neck B6,L7 15 L ant. cerebral - ant. communicating junction none 0 16 Rant. cerebral -ant. communicating junction general and back of neck 0 17 anterior communicating severe general 0 18 ant. cerebral - ant. communicating junction sudden coma 19 (1) ant. cerebral-ant. communicating; (2) Land (3) R carotid, unruptured none 0 20 R ant. cerebral; 3 previous hemorrhages severe, R eye and forehead 0 2T (1) Rant. cerebral, unrupturecl; (2) Rpost.inf . slight headache months-+sev. 0 cerebellar, ruptured 22 (1) Rant. communicating; (2) Lint.carotid in sinus; none 0 (3) L post. cerebral -post. communicating 23 (1) Lant. cerebral -ant. communicating junction; (2) L int. carotid ( both unruptured ) no details g!ven 24 ant. cerebral or ant. communicating above sella bifrontal and bitemporal 0 25 R anterior cerebral none 0 - --V- -+H 1st signs + several d -0 ld -- + -- + -- + -- + -- + -- + -- .__ + - + -- ~ 8d 68 o 1 y _. 3d hours -- - - + -- -+ -- + -- - 3d 12 y 2m 2w 3w 9d 6d ~ ~ 1y-.3m - 0 surgery -- ~ 8.5 y -- 0 necropsy -2y ---- + sucloen cleatli + -- + sudden coma - l l y ~ 10 d 0 necropsy - 0 + 0 + 0 no details 2y 2m -- - *: not until fatal hemorrhage (# 12); for other sym:;bols, see first part of this Table FROM TABLED: ANEURYSMS OF MIDDLE CEREBRAL ARTERY -#1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 IB 19 ~ 21 22 LOCATION OF ANEURYSM PAIN oculom . R middle cerebral (mvcotic. in brain) R middle cerebral in brain R middle cerebral in Sylvian fissure and occipital R middle cerebral between ant . cerebral & 1st branch R middle cerebral 2 .5 cm from origin L middle cerebral at entrance into brain R middle cerebral in Sylvian fissure L middle cerebral 4. 5 cm from circle of Willis L middle cerebral 3 cm from circle of Willis small R branch of middle cerebral in S:zr:l. fissure R middle cerebral R middle cerebral R middle cerebral at 1st branch R middle cerebral in Sylvian fissure R middle cerebral in Sylvian fissure 3 unruptured on L middle cerebral and 1 ruptured on R anterior cerebral L middle cerebral, 2 cm beyond origin L middle cerebral at 1st branch (1) bilat. at 1st branch of middle cerebral; (2) on anterior cerebral; .(3) on tip of basilar R middle cerebral at 1st branch both middle cerebrals at ant. cerebral Junction R middle cerebral at 1st branch none noted headaches frontal R frontal frontal several days headache sudden coma dull frontal mild gen . ~ sharp backofne.ck sudden coma frontal sudden death viol ent R head back of head and neck headache R6 0 0 0 0 0 0 0 diplopia 0 0 none - severe, generalized none 0 0 severe bifJgn~ he~dache, neck an ac -ac e none none none 0 0 0 0 Symbols as in other parts of this Table; :B = bila.te.ra.l; 3 - 0 3 0 --- -+ -V H 1st signs 2d - + hours -- ,_ 24 h + - _Q_ 8d -- + 2m -+ 5d - + hours 0 """+ 15 y - --:;:- ly~5w -- + 12 h - + 2d -- + necropsy -- + 12 d -- + 3d -- -+- 5h --- + - + - 0 -- -- - = third nerve; 6 = sixth nerve; 7 = seventh nerve, 0 0 0 0 sudden death 1d necropsy 10 w necropsy necropsy necropsy 44. Vascular Conditions Table 44-6 / 1519 (continued) F ROM TABLE F : ANEURYSMS OF POSTERIOR CEREBRAL ARTERY It LOCATION OF ANEURYSM PAIN oculom. 1 2 (1) R post . cerebral; (2) R middle cerebral (1) L post . cerebral - post. communicating junction ; (2) int. carotid in sinus; (3) ant. communicating frontal 0 none 0 PAIN oculom. H - -V -+ -- - - 0 1st signs 24 h necropsy F ROM TABLE G · VERTEBRO - BASILAR ANEURYSMS # _1_ 2 3 4 5 6 - 7- 8 9 10 11 12 14 13 15 16 17 18 19 20 21 LOCATION OF ANEURYSM L OCCiQital Qain occieital headaches severe sub-occieilal severe headache frontal headache violent occieitaI L vertebral anterior basilar R side of basilar 2 cm sac at basilar -eost . cerebral junction junction of basilar and :eosterior cerebrals R vertebral near :eost. inferior cerebellar (1) R post. inf . cerebellar, ruptured; (2) anterior c e rebral at anterior communicatin~, unruptured anterior tiQ of oasilar basilar at 5th nerve origin (5th n. lifted) ant . :eart of basilar ( 5th nerve com:eressed) L ant. part of basilar (5th nerve compressed) basilar at L 5th nerve origin ( nerve com_ere ssed) (1) basilar R; (2) both vertebrals much dilated; (3) bilateral diffuse carotid L vertebral enlar~ea, basilar bulging to R basilar R ( 5th nerve comEressecl) basilar R ( 5th nerve com,eressed) basilar R ( 5th nerve com:eressed) basilar R ( 5th nerve compressed) (1) basilar at sup. cerebellar; (2) bilat. int.carotid R ve rtebral, unruptured basilar R (5th nerve compressed) Symbols as in first part of this Table ; 3 = third nerve; 6 H -- _Q_ V B6,L3 ,_Q_ diplopia 0 0 0 L3 1 6 + + 0 0 0 + + + + - - 0 no details - none 5th nerve 12ain L mouth&.tongue 5th n.eain in ey_e,forehead, jaw 5th n. pain in chin&.upper jaw 5th n. L manaiblc, cheek, tongue 0 0 0 0 0 necropsy 3y_ 0 ( ) 17 y_ 0 ( ) 1.5 y ( ) ( ) 2m none none trigeminal pain tri~minal :eain trigeminal _eain tri~minal _eain no details given none 5th n. pain L manaible &teeth 0 0 0 0 0 0 3y 0 0 0 ( ) 5w 0 ( ) ly () 0 4y 0 0 5 y_ 0 ( ) 4y_ 0 aiplopia - 1st signs Sm 1 y_ 2w 10 d 2w 4d cr- () () () () () ---- necropsy CJ 5 y = sixth nerve. THIRD NERVE Figure 44-2. Relations of the left internal carotid artery with neighboring structures in th e cavernous si nus. The sinus is shown with its lateral wall opened. Note especially the course of the third nerve, and its relation to the carotid artery within the sinus and to the posterior communicating artery above the sin us. Also no te the position of the fourth, sixth, and ophth almic fifth nerves in the parasellar area. (Slightly modified from W.B. Hamby, in lntracranial Aneurysms [Springfield, Ill.: C.C. Thomas, 1952]) 1520 I V. Pupillary Pathology: Pupillary Signs in Various Diseases at their exit from the midbrain to medially in the cavernous sinu (see Figure 3-95). In contrast a · the third neive in the cavernous inu approaches the superior orbital fissure it plit_s into its superior and inferior divisions. The pup1l_lary ~b~~s here are distributed mainly to the mf~nor d1v1s1on. _At_ and beyond the superior ?rb1tal. fi ure (w1thm the orbit) they may be mtermmgled with the somatic motor fibers or may torm a uperficial , independent, and sharply local1zed bundle all the way to the ciliary ganglion. The_e anaton:iic variations explain why part of the pu~1llocon tncto_r fibers can escape injury in some patients but not m others with third neive lesions in the cavernou inus, the superior orbital fissure, or the orbit. (c) Supraclinoid Aneurysms of the Anterior Part of the Circle of Willis At its emergence from the ca rnou ·inu the internal carotid artery gives off the ophthalmic art ry· and then the carotid divides, giving ri e to the po terior communicating, anterior choroidal, ant rior cerebral, and middle cerebral arteries (Figure 44-4). The e bifurcations are favorite sites for saccular aneury m to develop. Th e supraclinoid portion of the internal carotid artery lie beneath and lateral to the optic neive along which it courses to about the position of the chia m where it turns upward. Aneurysms at the bifurcation of the carotid with the more rostrally directed arteries therefore bring about afferent pupillary deficit when they damage the optic neive, chiasm, or tract. They may push the chiasm sideways and elevate it; compress the olfactory s -------,,B---------- ---- -------1 71--- - - - -...,_ ' __...,~,,,,~-;;;_:,",-=--,,..::--=-...----:;;;--:":---:;;;;a=;-;:::::::::::::::;;==;;:::;==---, '--'-'- -~'-',~. . ~, ✓.... ' - ~-- - - - - - -- - - -- ~ 6 1 - - - - - -- - ~~,, ____ . .~J--~,----,~~-- 51----- - - - - - - - - -- - - - - - - - - - - - - - - - - 1 s --------, C-----------------1 \ 71--- - - - ,:----:-----=---=-=-=--=--;;;;;;===:::;;:::::;;;;;;;::::;===::-i ✓-, t 61---------''.._✓.,.,,- ,? ' , _ .... "'\ / .... .\ /''"\ ,,... - -- 'vl'- 'G...., ..........,_,,.,... .,....,.,....... ..,,,,. ...... ,,,~.... ...... ____ _ ~51--- - - - - - - - - - - - -- - - - - - - ~ ~4 bmm-n-nTTTTTTbmnmnTTTTTTmrrrmrrrrmrri'mmmfmrmmrnmrmmrmmmmrmmmmmm,rmmrml o., sec.-- tract and the pituitary-hypothalamic a rea; and e_rode the ~ella or the optic canal (causing proptos1s and unilateral blindness). True aneury ms of the ophthalmic artery within the orbit are rare; but many cases have been described by this name. ln most of them there probably were enlarged orbital veins due to carotid-cavernous fistulae (Walsh and Hoyt, 1969). Consideration of the various visual field defect and other ocular signs brought about by these aneurysms exceeds the purpose of this book (see summary in Table 44-5 a nd case material given by Dandy (1944) as examples, as shown in Table 44-6; for a more detailed account the reader is referred to Walsh and Hoyt s text 1969). The third and sixth neives are occasionally affected in patients with large aneurysms that extend posteriorly from their origin on the rostral part of the circle of Willis. Head pain and other features typical for supraclinoid aneurysms will be described presently in connection with aneurysms of the internal carotid-posterior communicating arterial junction. (d) Aneurysms at the Internal Carotid-Posterior Communicating Bifurcation These common saccular aneurysms are the most important ones from the point of view of pupillary pathology. They are the occasional cause of an isolated large, inactive pupil, as in Figure 44-3. The ominous possibility of aneurysm haunts the background of the examiner's mind whenever the cause for such a pupillary defect cannot be pinned down beyond doubt as a tonic pupil. Typical syndromes due to Figure 44-3. Parasympathetic deficit due to a supraclinoid aneurysm. The patient was a 28-year-old woman who had frequent headaches, worse when she was under emotional tension and improved by aspirin. Corrected vision was 20/20 in each eye, with normal fields and fundi. Two to three weeks before examination she developed " terrific he adaches," which were dull and teadily throbbing. They were located mostly behind the right eye and in the right temple. Skull X-rays and extraocular movements were normal, but (in room light) her right pupil was larger than the left one. a nd accommodation was slightly reduced in the right eye (near point at 1.4 cm on the left and at 13.4 cm on the right side). The patient had no other complaints, and the neurologic examination wa negative. The pupillogram showed that both pupils were large in darkness. On the left ide all reactions were normal (broken lines), but on the right side the light reflexes were reduced (solid lines). They were, however, neither delayed nor prolonged, and there was no response to instilled mecholyl: in A and B her reactions are shown without th e drug, and in C I hour after bilateral instillation of three drops of a 2.5% solution of mecholyl. o contraction had taken place in either eye. Since there was no evidence of tonic pupillary reactions, and because of the ipsilateral headache , the patient was studied further. A right carol id arteriogram revealed a large aneurysm at the carotid-po terior communicating artery bifurcation. Comment: In this patient the partial internal ophthalmoplegia was the only objective neurologic defect. She had been referred to the laboratory because a tonic pupil was suspected; but the headache did not fit thi picture and neither did the pupillogram. 44. Vascular Conditions / aneurysm and typical tonic pupils are, of course, quite different (Table 44-7), but not all cases are typical. The special features of the syndrome brought about by unru ptured aneurysms at the internal carotidposterior communicating artery bifurcation are (1) normal vision (unless the aneurysm is very large, (2) the frequent presence of an isolated third nerve palsy, and (3) head pain that is not the result of involvement of the trigeminal nerve. Head pain may precede all other signs; and since it is severe, it often brings the patient to see the doctor. This pain is quite different from the occasional headache the patient may have had before. It is unilateral and sharp, boring in character. Usually it is located in, behind, and around the eye, radiating above the brow and to the tem ple. After a time it may remit, but later it will return; and repeated episodes of this pain sometimes have been misinterpreted as migraine or ophthalmoplegic migraine (see publications marked with a triangle in Table 44-4). Because the pain is felt around the eye, forehead , and temple, it was often ascribed to involvement of the ipsilateral fifth nerve. However, patients with aneurysms of this type have pain quite different from trigeminal pain, in most cases without loss of trigeminal function in the painful area. Neither is there paralysis of the postganglionic sympathetic fibers to the eye and forehead that travel with the ophthalmic branch of the fifth nerve. Ant . Communicating A. I M>'~~~~:: :':. A. / •_'."'."'."_IIIIIIIJ..lllllalllll~ / st riate Aa . / : :.. 3rd Nerve : The special vulnerability of the parasympathetic pupillary fibers in the third nerve is obvious from their anatomic cour e. The third nerve enters the cavernou inus just below and lateral to the internal carotidposterior communicating bifurcation (Figure 44-2). The nerve is here anchored to the dura by connective ti sue septa, so that it cannot slide or give. This worsen the stretch and pressure exerted upon it by an expanding aneurysm. Since the pupillary fibers run in the me ial and superior periphery of the nerve, they are the mo t likely to be affected early and the lea t likely to recover after surgery. Pupillary sparing is extremely rare with aneurysm at this location ( ee Chapter 22). (e) Mechanisms of Third Nerve Damage Several factors can contribute to impairment of the third nerve. (1) Mechanical stretch and pressure, especially when the nerve is flattened again t an unruptured aneury m. Apparently, the nerve can adju t to thi type of injury to a degree, becau e these le ions often look chronic in patients with a relatively hort hi tory of third nerve pal y (Hyland and Barnett, 1954; Hender on, 1955; Bottrell and co-workers, 1962; and other ). (2) Bleeding into the nerve with econdary fibrous connective tissue proliferation and adhe ion to the ac, due to leaking or ruptured aneury ms. (3) Ischemia due to impairment of the nerve ' intrinsic arterial blood supply by one of the above type of damage . .... •············~•..•.{·····························.. . a .. .. : : ,:u, A. ,:r•···•. . . . \ ::~{i:·::·>i:_;::·::.=.,\· . . .... ··· •· ... Ant . Choroidal A. ··••l \ ___ ,r l Post. Communicating A . • ~ Post. Cerebral A . ~ : : :: Sup. Cerebellar A : ! Pontine Aa . 5th Nerve Bas il Labyrinthine A. 6th Ant. Spinal A. · · ·•. . .\.. \.-~.Y-?•f // ........ ::·.-:::.-::::.::::::::.::::.::;::~~D~\::·::~:::::::::::::·~:::·>•••• ·•••••• 1521 Post . W . Cerebellar A. Figure ~-4.. Arteries .at the base of the brain. as see n from below. Note especially the relations of th e third ne rve with the po terior communicating, posterior cerebral, and superior cerebellar arteries. 1522 I Table 44-7. V. Pupillary Pathology: Pupillary Signs in Various Diseases Pupillary and other defects due to intracranial third nerve damage, compared with tonic pupil syndrome FEATURES LOSSOF CONSCIOUSNESS CAUSE OF INTRACRANIAL 3rd NERVE IMPAIRMENT ANEURYSM TUMOR TRAUMA sudden gradual sudden or delayed at onsetorearlier; uneven, worsening patient unconscious ipsilateral, severe course; ipsilatcral or general may be present sometimes (late) may be present never never OTHER NEUROLOGIC IMPAIRMENT almost always present usually present always present none, or diabetic neuropathy none except defec tive tendon reflexes LA TERALITY OF OCULOMOTOR DEFICIT uni> bilateral, according to site uni> bilateral, according to site uni >bilateral unilateral *2 unilateral *2 EO - MUSCLE DEFECTS usually present usually present usually present always present none SIG S OF "MISDIRECTION" ON RECOVERY common common common rare , if ever yes*3 PUPIL IN ACUTE STAGE large, sluggish or fixed *4 large, sluggish or fixed *4 large, sluggish or fixed *4 spared large, fixed or tonic ONSET HEAD PAIN PUPIL IN CHRONIC STAGE SIZE ( in room light) after re-innervation, moderately dilated or smaller after re-innervation, after re-innervation, moderately dilated moderately dilated or smaller or smaller DIABETES TONIC PUPIL acute or subacute acute or subacute at onset; ipsilateral and severe none*l as in good eye smaller than in acute stage LIGHT REFLEXES none or reduced but not delayed none or reduced but not delayed none or reduced but not delayed as in good eye none or delayed and tonic remnants REACTIO none, remnant or "recovered", brisk *5 none, remnant or "recovered", brisk *5 none, remnant or "recovered", brisk *5 as in good eye none, remnant or supranormally exten sive and tonic TO NEAR CONJUGATE GAZE brisk contraction brisk contraction brisk contraction none none AC COMMODA TION as pupil to near as pupil to near as pupil to near as in good eye slight slight slight none reduced or extensive, tonic marked CHOLINERGIC SUPERSENSITIVITY *l Sometimes a vague ache in or around the eye is reported; and occasionally ciliary spasms cause pain on near vision in the later stages. *2 Sometimes a later attack will affect the second eye, but bilateral onset at the same time apparently is extremely rare. *3 The tonic pupil syndrome results from faulty regeneration of fibers destined to the ciliary muscle into the iris; but extraocular "misdirection" signs do not occur in tonic pupils (no constriction on lateral conjugate gaze) . *4 Pupillary "sparing" is very rare, except for partial sparing in intracavernous lesions (see text). *5 The reaction is only apparently recovered: it accompanies the convergence movement during near vision and is due to 3rd nerve "misdirection'; EO- MUSCLE DEFECTS= extraocular muscle defects. (4) Perhaps edema and intra-neural hemorrhage, brought on by obstruction of small intrinsic veins. After the acute phase, recovery is slow and incomplete, even after a single paralytic attack. This contrasts with the third nerve palsy due to ophthalmoplegic migraine in which the early paretic episodes usually are short-lasting and followed by rapid fading of the motor defect. Permanent paresis develops much later in ophthalmoplegic migraine, after many such fleeting episodes. Some patients who undergo surgery after ophthalmoplegia has developed due to an aneurysm regain full ocular movements, but only when the operation is done less than ten days after the onset of the third nerve palsy (Bottrell and co-workers, 1962; Grayson and coworkers, 1974). It should, however, be noted that the term " recovery" in some statistics referred to the absence of complaints on the part of the patient. Often this is not at all synonymous with functional integrity of all muscles innervated by the third nerve. For example, in Hepler and Cantu's series of twenty-five long-term survivors of bleeding aneurysms with third nerve palsy there were only five patients who were troubled significantly by diplopia. But there was not a single one whose intra- and extraocular motor system was unimpaired. The " third nerve misdirection syndrome" is a common sequel to oculomotor palsy caused by aneurysms. A few weeks or months after the paralytic attack, adduction of the eye again becomes possible, but it is accompanied by abnormal raising of the lid; and vertical eye movements remain poor or absent. The dilated pupil begins to become smaller, and in time it may become smaller than the normal pupil. It begins to contract again when the patient looks at a near point, while the light reflexes usually do not recover. This pupillary behavior has been confused with the Argyll Robertson syndrome. The difference is that the pupil constricts not only during near vision but also when the eye is adducted in conjugate lateral gaze, as well as during attempts at looking up or down (Figure 44-5). The relative miosis and pupillary constrictions during ocular adduction also have been mistaken for partial recovery of the injured pupillary fibers, but they are due to abnormal reinnervation. The differences between these conditions and their mechanisms are considered above (see Chapters 11, 23, and 43). Walsh (1946) pointed out that a "misdirection syndrome" in such patients proved that the paralysis had not been due to simple, short-lasting pressure upon the third nerve but that its fibers actually had been inter- 44. Vascular Conditions / 1523 Papilledema, bilateral pyramidal signs, and brainstem and cerebellar signs result ( dysphagia, dysartria, unsteady gait, vertigo and dizziness, tinnitus and deafne , and gaze palsies and nystagmus). Severe bilateral occipital headache may be pre ent, and trigeminal pain develops when the fifth nerve is compressed. In contrast to the pain caused by supraclinoid aneurysms the trigeminal pain is associated with typical fifth nerve sen ory deficits, that is, paresthesias and trigger zones with tic douloureux attacks of trigeminal neuralgia. However, the pain is not accompanied by postganglionic oculosympathetic paralysis, as is found in patients with trigeminal lesions in the middle fossa or cavernous sinus. Pupillary parasympathetic damage may be present in patients with more rostral lesions, due to involvement of the pupilloconstrictor fibers that run in the third nerve. Trobe and co-worker (1978) described two cases with isolated third nerve palsy due to basilar aneurysms. These cases were also unusual because of their chronic course and the absence of pain. Occasionally there is bilateral miosis due to pontine involvement (Smith, 1924). rupted. "Misdirection" almost never occurs upon recovery from short-lasting, ischemic diabetic ophthalmoplegia. Walsh also noted pupillary contractions to mecholyl in patients with ophthalrnoplegia due to aneurysms. This hyper ensitivity further indicates that the parasympathetic nerve path had been interrupted (see Chapter 11). We also found supersensitivity in such cases, but it was less marked than in patients with postganglionic parasympathetic lesions (the reason for this difference is discussed in Chapter 11). (f) Aneurysms of the Vertebro-basilar Arterial Tree These aneurysms are much rarer than those of the carotid artery and its branches (Figure 44-1). Small ones may remain asymptomatic unless they rupture. Larger ones at the rostral tip of the basilar artery, that is, at the basilar-posterior cerebral or basilar-superior cerebellar bifurcations, can catch the third nerve on one or both sides as it passes between these arteries. More c~udally the fifth nerve roots may be trapped or the sJXth, seventh, or eighth nerves on one or both sides. Large sacs are embedded in the ventral surface of the b~ainstem, and they may exert sufficient pressure to distort and occlude the aqueduct and fourth ventricle. B. Other Vascular Malformations 1. Arterio-venous Malformations . Anot_her cause of primary subarachnoid hemorrhages 1s bleedmg from an arterio-venous malformation. These lesions are tangles of coiled, abnormal blood vessels of variable caliber and wall thickness, with one or more hypertrophic, dilated feeding arterie and draining veins. The vessels that make up the mass are neither typical arteries nor veins. They continue the embryonic pattern of blood vessels where blood flows directly from arteries Figure 44-5. Third nerve damage with " misdirection dyskinesia" due to aneurysm. The patient, a 36-year-old woman, had had complete right-sided third nerve pal y due to a upraclinoid aneury m. The aneurysm had been clipped 3 mo nths before examina tion and the eye movement had improved. Adduction wa normal while upward gaze wa moderately and downward gaze light!~ reduced. The right lid was raised each time the patient looked down or adducted the globe. The right pupil, al o, showed th e pseudo-van Graefe type of " misdirection synkinesia'·: in darkne and straight-ahead gaze, the two pupil were equal. Light renexe were reduced on the right side ( olid lines, A); but du ring the near-vision reaction the right pupil con tricted more exten ively th an the normal left pupil so that it became the mailer one (8 ). This relative light-near dis ociation differed however, from the Argyll Robertson yndrome. When the patient adducted the eye in conjugate gaze to the left, the right pupil con tricted, while the normal pupil did not (C); and the ame happened when he looked down {D) or up (E). Down-gaze was mo t effective in bringing out this pathologic response. ote that the latent period for contraction and redila tion of th e light reflexe were not noticeably prolonged, and that the right pupil's light reflexe were not tonic in shape. Similarly, after contraction due to eye movement , the pupil redilated promptly. into veins without the interposition of a capillary bed. Arterio-venous malformations may develop in all parts of the brain and spinal cord or in the orbit, but the larger ones are found most often in the cerebral hemispheres. They may be seen on the surface of the hemisphere but usually they extend deep into the brain ti sue as a wedge-shaped mass. They vary in size from minute tufts-hardly visible to the unaided eye-to huge masses of tortuou , dilated vessels that occupy a large ""'"' "' sB,-- - - - - - - 1 - - - - - - _ J ;~-::r-~:~:=-==--=-=---=-=-=--=-=-=---=-=-=--===-= --,==f-t-::-~-~~=-=-=---=-:-~--~-~-~---==-=-~~~J n~ar vision 2 ., __ _ ... ____ , 3 D-1-----_--._---_··_-._--_c..:::::··,,,_ 2 ♦ ~ lookina dollJn _.,---------- - ---..-- L--- sE -=-+r:.._____________ .: : :--------.-.--.- _:-. __--·-..·-···--=y=::-:::.:-:::-===--==--=--tJ-------_j ; ====:-I ~ 2 o.,se(. -+ loolcina UD - ... --r 1524 I V. Pupillary Pathology: Pupillary Signs in Various Diseases part of the hemisphere. They have been described under many name such as varix, cavernoma, angioma, or hemangioma. The e differentiations (the validity of which i disputed) do not concern us here. Often the e malformation fir t cause neurologic ign by cerebral or subarachnoid hemorrhage. Seizures are a frequent pre en ting ign. Before rupture, the signs may re emble those of aneury ms, occasionally including propto i and sy tolic bruit over the carotid in the neck or ver the eye, and p riodic migraine-like painful attacks, with or without ophthalmoplegia. There i no en e in enumerating the different pupillary defect that can be caused by these lesions. Obviou ly, the pupillary center or pathways can be damag d by a le ion situated nearby. One point should be k pt in mind: the effects of a vascular malformation need not b limited to the part of the brain it occupies. Pre ure upon urrounding areas; subarachnoid or intracerebral hemorrhages; interference with venous outflow and ec ndary hemorrhages; anoxia of parts of the brain from which blood is hunted by the vascular mass, or brain hift all can cau e secondary damage at some di tance from the le ion . As an example, in cases with occipital va cular le ions and cerebral hemianopsia, a hemianopic decrea e of the pupillary light reflex is ometime blamed on the occipital lobe defect as such, ugge ting that the light reflex path runs via the cortex ( ee Chapter 17). However, the optic tract and third nerve, their intrinsic blood supply, and the midbrain can be damaged by the secondary consequences of these lesions. 2. Anomalous Vessels It is not uncommon for the vessels of the circle of Willis to be distributed anomalously. For example, the posterior communicating artery may be much thinner--0r much larger-than is normal; or the vessel may be missing entirely on one or on both sides. It has been thought that such asymmetries set up hydrodynamic stress favoring the development of aneurysms. But this view has not received general acceptance because statistical studies failed to show a distinctly increased incidence of aneurysms in these individuals, compared to those with a symmetric circle of Willis. In rare cases, a primitive embryonic vessel may persist. For example, in roughly 1 out of 100 to 1 out of 500 arteriograms, a persisting carotid-basilar anastomosis is found. ln the twenty-somite (26-day) stage of development the longitudinal neural arterial plexus receives its main blood supply from the primitive trigeminal artery, an anastomosing branch of the carotid artery. Later the longitudinal plexus organizes to form the basilar artery, receiving blood from the vertebral arteries; and at the 45-day stage the carotid-basilar anastomosis is obliterated and replaced by the posterior communicating artery. The clinical signs produced by pressure of such large persistent embryonic vascu lar connections resemble those due to aneurysms, including in some cases bouts of head pain and oculomotor palsy. Madonic and Ruskin (1962) described an interesting patient who had recurrent oeulomotor paresis with the pupil spared. 5 i-;;;;-~-_-=_-=_-;;;;_,;------------------ - ----1 1+1----- 3 A----=-=---=-~~~-----,--,~-~,-~~-~ lt------------------------------, 5 +It3 --' '/-----1 t El ~,~~~~~==~~~~~~=~~~~~~~ 0.1sec. _. Figure 44-6. Third nerve lesion due to aneurysm. The patient was 48 years old and had a long history of bilateral migraine but was otherwise well. A year before examination she had had an episode of diplopia and blurred vision. This cleared after 3 to 4 months but then recurred 6 weeks before examination. This time the patient noticed slight drooping of the left lid and some leftsided supraorbital pain that was accentuated when she looked up. Except for the ocular findings the neurologic examination was negative. There was paresis of the left superior, inferior, and me- dial rectus muscles and the inferior oblique, and slight ptosis. The left pupil (broken lines) was slightly larger than the right one (solid lines), and the light reflexes were slightly diminished but not tonic on the left side (see small arrow ). Vision was unimpaired. Arteriography hawed an intracavernous aneurysm on the left side, arising from the internal carotid artery proximal to the origin of the ophthalmic artery. Comment: Note that the timing of the reduced light reflexes on the left side was the same as on the normal right side. 44. Vascular Conditions / 1525 C. Intracranial Aneurysms versus Pupillotonia Becau e of its a ociation with intracranial disease, mydriasi carries an ominou connotation. It ha been o ur experience over the years th at most pati e nt who were referred to u because they had marked anisocoria were sent because of' an enlarged pupil. ' Quite often there wa nothing the matter with the large r pupil. These were patients with the common "central eesaw" anisocoria ( ee Chapter 28), and occa ionally with sympathetic paraly i or spastic mio is on the side with the smaller pupil. A special case for wo rry i pre ented by th e patient with a dilated, luggish, or fixed pupil that developed suddenly, together with accommod ative pal y. Both the contractions to light and to nea r vi ion are poor or abolished, and the affected pupil fail to contract to 2.5% mecholyl or to diJ ute pilocarpine (Figure 44-3). A freshly dilated pupil is rightly a matter for concern, even though it i. rare for an ambulatory patient to prese nt this way. If the patient is otherwise neurologically in tact, then aneury m become a remote diagnosi , and an acute postganglionic le ion is u pected . Additiona l oculomotor impairment, even if very light rule out pupillotonia (Figure 44-6). However, it is difficult to distinguish isolated preganglionic pupil involvement from acute pupillotonia (Figure 44-7, A). There may be residual light reflexe in either ca e, and there will be no light-near dissoci ation at thi early tagc. Accommoda- tion is likely to be defective in both conditions. A slight contraction to weak cholinergic drugs (if present) proves that the iri i not damaged, and that the patient has not used atropine-like ubstances to dilate the pupil. If the cholinergic sensitivity were more distinct, it could be said with confidence that the pupil is tonic; but slight supersensitivity is compatible with a preganglionic (third nerve) lesion. . . Today the availability of brain scans and d1g1tal subtraction angiography makes the evaluation of such problem infinitely easier and safer than it was ju ta few year ago. Once an aneurysm has been ruled out with these technique , the clinician can rest more ea ily. Before any studies are undertaken, however, certain rule can be applied. The first and most important question is whether the patient ha pain in the eye or head. A tonic pupil never causes pain. Occasionally, the patient will describe a vague ache, or a " funny feeling" or "pulling sensation" in the eye, mostly during the early stage of ciliary ganglionitis; and later tonic ciliary spasms may give rise to complaints of cramping pains during attempted near vi ion. These can, however, be differentiated from true headache; and a patient with a dilated, sluggish, or fixed pupil and ipsilateral headache in the fronto-temporal region hould be considered to have an aneurysm or (le likely) other intracranial pathoJogy until proven 9>---~-81 J..rJ 7,__ \\ lf ~ -- r - -- --t---jf-----1-- +-- - - - -~ 3- - - r - -- - -t--ll------t-- -1-- - - - -~ Zr Lr Lr S~A~~- -- - - - - - - - - t ~ l:: 7 ,.._ .....::s:,, 6 t--f -~ ' c--- - 5 ~, ________ -- -------- ---•-- I -------------------- ✓- ,,-~ - -- - near ------- 3 "" """ I - - """ o.,secona - Figure 44-7. udde n internal ophthalm plegia developing into classic tonic pu pil yn drome. The pauent wa. a :?6-year-old woman who uffered from frequent ten ion headache .. One day she suddenly noticed blurred vi ion in her right eye. and when he looked into the mirror, ,he aw that her right pupil Y.a much larger than the left one. he wa frightened b} thi . and we nt to see her doctor. She . aid that he had a " peculiar., <.en ati n in and around her righ t eye. The pupillogram. taken I week after the beginning of thb condition. ho,,ed partial I of reacllon to light and to near-vi. ion on the nght ide (. lid line . 'and '). She al o had reduced accommodation on the right tde. 0th rw1 her eyes we re normal. and there Y. ere no neur I gi ien . Be• cau e of th e ab. ence of di tinctl I me feature in her puptll ry findings , or of disturbance of deep tend n relle,e . and be au e of th e complai nt of peri-ocular di omfort, further Y. o rJ..up w 6- 5 Zr ,, ., 2 8- -·' - \ __,,;,,,,,.--' --=- -.- / \ ·, / lr "-' I "' "' -- ----- _____ \ \ '· __ , / lr -~~82 _ , 1- 6- ~ 5 If ' , -- 3 ,_ --- --- ,_ ,___,, , I _. --------- -- -- near a1seeonti ... con 1dered._ However. the patient appea red p e rfectly hea lthy, and her complaint. appeared t fit the de cri plion of se nsations _ · db . . expe nence omt: patient in the acute tage of ciliary gangHonitis. There wa. n real headache and the extraocular movements were perfect. Further workup therefore wa limited to walchf J ·t· · d d h . · . . u wa1 ing. An d in et! . t e pauent de-.eloped a classical tonic pupil syndrome during the follo'\loing month . The record B wa taken 6 m nth a ftc.:r -\ . In darkn the righ t, pathologic pupil now was malkr than th n rmal, ldt pupil. 1 · . and lighl reflexe had d een~ rate d 10 tom t~ce ( B ) . The nght near-vi ion contraclion, though me ten •"e_. had bee me m re pr n unced lhan the best hght refle of the nght . . pupil. and II utla ted the norma I pup,·,,s near-\l 10n ontrac11 n b\• 1.eral econd ( B') • Th e mec ho Iy I te t (not h n) had h c me po. itil.e. 1526 / V. Pupillary Pathology: Pupillary Signs in Various Diseases otherwise. The absence of pain doe nor rule out an aneurysm, but the chance are much reduced. Further the extraocular movements remain normal in the tonic pupil syndrome while patients with a dilated pupil but no other oculomotor loss due to an aneurysm are rare. The sympathetic pupillodilator fiber also remain untouched in tonic pupil but may be damaged by infraclinoid le ion . Tonic pupil therefore dilate well to cocaine and paredrine, but in patients with aneurysm the e reaction may be mi ing. The deep tendon re- fl~xe~: in .c?~!rast, are often red~ced ?r lost in patients with Adie s yndrome but not m patients with mydriasis due to intracranial aneurysms. In general, pupillotonia is not a defect that makes the patient ill. The large pupil often is discovered accidentally· and-aside from some blurred vision due to the accommodative loss and worry about the condition-the patients typically are in good health. While this may be true in some patients with aneurysms that are unruptured, leaking aneury ms are usually seen in persons who feel ill and have a headache. D. Migraine Variants 1. Summary Migraine has been known for more than two thouand year , but the underlying disease proce still has not been clearly determined. 2 From ancient times this my teriou malady has plagued untold thousands of victim ; and it comes in a bewildering variety of forms with details varying so much from patient to patient that an attempt at delineating distinct types inevitably carrie with it a degree of over irnplification. Further, "migraine" ign are mimicked by a number of other conditions; and confusion reign in the nomenclature used as well as in the hypothese advanced over the years to explain the different defect . In broad terms, cla sic migraine attacks have come to be thought of as associated with periodic alterations in cephalic blood vessels, both intra- and extracranial: an early phase of vasoconstriction, followed by vasodilation with edema of vascular walls. According to this view, the vasoconstriction period with ischemia of localized areas of the brain causes an aura of sensory or motor defects such as the well-known scintillating scotomata; and the following vascular enlargement is accompanied by severe, throbbing headaches, nausea and vomiting, or other signs (Table 44-8). 3 Usually but not invariably the headache is unilateral, the condition runs in families, and many attacks occur at regular or irregular intervals against a background of good health. The attacks tend to begin in childhood or adolescence, and often abate toward later middle life. In many patients they can be precipitated by physical or mental stress; by ingestion of alcohol or substances contained in certian foods; by vasodilator drugs such as reserpine, nitroglycerine, or histamine; or by withdrawal ofvasoconstrictor agents such as caffeine or nicotine. 2. Riley's (1932) and Critchley and Ferguson's (1966) reviews describe this fascinating history. 3. Whether these vascular changes are primary and bring about the neurologic (and other) defects, whether the reverse is true, that is, that the vascular changes result from primary neurologic events, or whether both the vascular and the neurologic (and other) signs are elicited together by a still unknown common cause is still disputed . Further consideration of the different views about these mechanisms exceeds the purpose of this book. A regards the pupil the findings vary, and mydriasis or miosis may accompany the attack, together with localized or general shifts in autonomic innervation. For example, a blanched face and contracted temporal artery may go together with ipsilateral mydriasis, as observed in his own migraine attacks by Du Bois Reymond in 1860. In other patients or in a later attack in the same patient, when nausea, lethargy, bradycardia, etc., dominate the picture, the pupil may be small. Oliver Sacks in his book on migraine described such a case (number 51). "A 48-year-old man has had migraine since childhood, and also suffers from chronic tachycardia. He had been struck, therefore, by the slowing of his pulse during the attacks, and has observed that his pupils, normally large, become minute. I was able to confirm these observations while seeing him •n the course of an attack: there was striking pallor and diaphoresis, congested chemotic eyes, pinpoint pupils, and bradycardia of 45.' In addition to these occasional findings, pupillary defects are prominent in two variants of periodic headache, namely (1) "cluster headache" and (2) "ophthalmoplegic migraine." In "cluster headache" the attacks of pain are short and violent and are accompanied by hemifacial flushing, rhinorrhoea, and tearing; they occur daily or even more frequently-often with clockwork regularity-for periods lasting some weeks or months ("clusters"), interspersed with months or even years of remission. This type of headache is most common in middle-aged men. It is "benign" in the sense that it has never been found to lead to serious neurologic impairment or death. In recent years it has been confused with "Raeder's syndrome" because of a similar distribution of pain, and because in both conditions the ipsilateral oculopupillary sympathetic fibers often are damaged (see further details in Chapter 25). In "ophthalmoplegic migraine," in contrast, the pupillary defect is parasympathetic, as part of oculomotor paresis that accompanies the more severe painful attacks in this condition. 44. Va cular Conditions / Table 44-8. 1527 Migraine variants C01\1MON MIGRAINE: Periodic incapacitating headaches, uni- or bilateral and often familial, associated with prostration, nausea, vomiting and other physical or emotional signs, and occurring on a background of good health. "CLASSIC" MIGRAINE: Often familial periodic attacks of headache of migraine type, preceded by an aura of motor, sensory or other symptoms: visual, such as scintillations, phosphenes, scot.omata of variable density and size, hemianopsia or transient blindness; tactile, aural or other sensory impressions; alterations of sensory thresholds, of consciousness or of mood • BASILAR MIGRAINE: Attacks of usually bilateral prodromal visual loss, scintillations, etc. and brain stem signs (vertigo, ataxia, tinnitus, paresthesias, dysarlria, nystagmus); with vomiting and severe , throbbing bilateral ( mostly occipital) headache. HEMIPLEGIC MIGRAINE: Rare syndrome, usually familial, of migraine with mot.or or sensory hemi-deficit, commonly with mental confusion and with dysphasia when the hemiplegia is right-sided; hemicrania usually follows but may accompany or precede the motor defect; drowsiness may be marked. OPHTHALMOPLEGIC MIGRAINE: Rare syndrome of unilateral migraine headache without aura and not commonly familial; usually accompanied by nausea and vomiting, and followed by ipsilateral ophthalmoplegia involving the third, sometimes the sixth and seldom the fourth and fifth nerves (see this chapter for details ) . CLUSTER HEADACHE: Vascular headache without aura, nausea or vomiting and seldom with migraine family history; short bursts of intense pain occurring in "clusters", that is, regularly over days or weeks, with months or years of remission; bouts are accompanied by ipsilateral rbinorrhea, tearing, and often postganglionic Horner's syndrome on the affected side (see details in "SYMPATHETIC PARALYSIS"). MIGRAINE EQUIVALEN TS: Visual or other aura without pain (scintillations, hemianopsia, etc.); cyclical vomiting or "bilious attacks", with or without constipation or diarrhea; bouts of abdominal pain with nausea and vomiting; attacks of chest- or pelvic pain; bouts of fever; psychic defects, lethargy, mood disturbances; behavioral defects; paroxysmal vertigo or edema. -----------------------------------------------------------"SYMPTOMATIC" MIGRAINE: Migraine-like attacks of recurrent head pain plus other motor or sensory disturbances, found in patients with vascular malformations (angioma, carotid-basilar anastomosis), aneurysms of the carotid, basilar or posterior communicating artery; tumors ( especially occipital); temporal arteritis; basilar or carotid insufficiency, or glaucoma. 2. "Ophthalmoplegic Migraine" (a) Appearance In this rare variant of periodic hemicrania the headache usually is combined with ipsilateral third nerve paresis. Occasionally the sixth and exceptionally the fourth nerve is involved. I have tabulated the cases with third nerve damage available to me (up to 1974) in Table 44-9. 4 ln patients with 'ophthalmoplegic migraine" a pattern of periodic hemicrania with nausea or other signs usually is established some years before the first episode of oculomotor paresis occurs. Often only severe attacks are associated with paralytic signs, while fairly frequent minor bouts without motor deficit are interspersed. Most patients therefore have many painful attacks but relatively few paralytic ones. Only a few children develop an oculomotor deficit at the time of their initial attack, or have episodes of ptosis and diplopia that precede the full-blown bouts with pain. The pain usually 4. Ca_ es publi h~d since this table was drawn up were not added, since they did not alter the conclusions derived at the time. is located in the area of the orbit forehead, and temple, and it is intense. Reports on the frequency of attacks vary from weekly to once a year or even less often, but some of the e reports are difficult to interpret. In addition to the u ual vagueness and incompletenes of many description , most author counted as separate bouts the relatively frequent ordinary painful attacks whereas some counted only ophthalmoplegic episodes that occur at much longer intervals. In Figure 44-8 the information given by various authors is plotted (as nearly as po sible) in weeks. In a typical attack, the patient will develop one-sided headache, nausea, vomiting, and prostration. These symptoms usually are more severe and longer than in the nonparalytic bouts (see details in Table 44-9). Finally the headache abate ; and as the pain lessens, or shortly thereafter, the lid starts to droop and diplopia develop . The oculomotor palsy will be more or less complete, depending on the severity of the attack and on the number of previous paralytic epi odes; correspondingly, ...Table 44-9. lll "Ophthalmoplegicmigraine"and "recurrentoculomotorparalysis":Literaturereviewed N 00 YEAR I AlJTIIOR 0 .1 ? I TERM USED TO DESCIUBE CONDITION l4 !~~ __ONSET =§ 1"' e -:. C ,; -~ c:t .!:fl ti.. 1860 Jo77 1882 I 1863 1883 Fournier (Gubler) no recurring 3rd nerve paralysis Adams no paralysis of 3rd n. with intermissions Saundbv • me2rim with oaralvsis ol 3rd nerve Duboys no ocular paralysis llasncr + pc;rlodicnliy rccurringoculomotorpaJsy ..!lli.._ w;.1,1.... + periodicnlly recurringocu1ornotorpalsy l~b-1 ,1 + oculomotor paralysis ------rr---Rcmnk -,-.,-+ (d Thomsen) 188·1 Thomsen ... +? recurring o~ulomot.or paralysis 1865 Clarke + id. Snell) 1 lo85 Mnnz + periodic oculomotor palsy ~ Parinnucl&1\1al'ic ? recunen_t_ncuralgia and other pnlsv 1885 pnu~cr no periodic nuclear palsy 11:185 Saundby ? migraine with paralvsis of 3rd nerve 18!:i5 Snell ?+ recurring palsy of 3rd n. assoc. withmigr. 1885 Weiss no neriodic oculomotor onralvsis 1 1087 llinde& ?-.lover no periodically recurring oculomotor palsy 1807 Richter +? recurring oculomotor palsy 1887 Roosa + recurrent paralysis of motor oculi 1887 Senator + pel'iodic oculomotor palsv 1 1887 Suckling + n~;~~~:: ~~c~~~l~~;:.,c: uy temporary U::187 \Vnd3worlh -a Po. - ..12..,_ .J.2._ .Md____±...~ - - O _MG _7 ___ 7_ pP d-m + . _g .!L_ ...!L pP L-R ? 0 7 6 6 + 3d + + 18 18m 18m + + _ .1Q. _-_ .£!!._ __ o__ 0 O _ ~ _7_ 1_l_ ~ _!_ + 7 J_ _i_ + + O Jt]! _8_ ..§.±_ ...E1:1L + J~Jl. _8 _ .1.L .l:1...£_ + ➔ o"l8 L 2d-lw Jl.ai ~ __6_ ~-?- _1_ + +- Si!......£h._ ..1L ...J!£.1L i I + pP days _::_ pP 2d + + + DETAll,S or -,~ Q, jo J-2 d R weeks L 3w R ld-ws L 2-3m 8d-2m R lw L 4m L 1-2w L lw R weeks L 36h R 3-5d + NUMBER AITACKS --.? R !Od-lm 0"31 • ;nu O L l-2m _Q.!11.!J!::: 12 ..Pf..M._ _..:_ L 3w-ms 0"30 24 _!1._ ~ __Q_.1.l!!!...___ Qll 1.L_ _!a_~ ___:t_ L 8d O .Q_Q_ llm.. _3_~ + R 2-3m fil2. EYEIN INTERVALS _Y.ears ? ...l2.day.a..__ nonnal 6-8 monthsparesis ~g. ? 1/month normal 1/year mY.drlasls. -±:::ifYHt-n +paresis normn.l J-2/yenr paresis 6 weeks ? 4-6 weeks paresis each spring normal 2 vears normal 1 vear normal 6 mouths oaresis each year ? 3m - 1 5 y n -+paresis 1-2/year paresis 1=1 weeks n -,.. palsy 4 weeks no anal every 2 w + _QJ.§. _2 ___ 8_ ~ __2,_ R ld-2w paresis :;;;;;: 4~, died from cereb~al hemorrhag~: 3rd nerve embedded in fibrous mass 2 I OM spared· patient had syphilis JO years earller . . many !ewer drowsy, dizzy during attacks; 3rd nerve inv~lved only m ~~Jor bouts . ., 6 6 bilat. total ~thalmopiegla &proptosis, CNS signs; died: menmgeal hyper·emia many many attacks rela to menstrual cycle _ . . :-5 6 no pain in first attack· bouts became increasingly severe with nme manv __!!!!!!L squint became permanent after repeated attacks many many short-lasting attacks: oormaI next day ._ _ manv many father enilensv; naticnt eoUeosv after head trauma at 02:e 13 (see IUchter 1887) ~ many not clear whether pain and palsy colncldca . ~ ~ headaches since earliest chlldbood; attacks could be trrggered by alsohol many ~ periods of daily supraorbital pain, becoming less Intense in rece ■ t years 3 3 llrst bout L & L 7th n. palsy; f2 R with R 7th n.; H3 R with R 6th palsy 2 2 temperature 990F, pulse 96; lower left 7th nerve deficit manv many "neurotic" family; "migraine" and palsy coincided many many died from 1bc: tubercular granulations had invaded 3rd nerve at base many many no nnin in first attack......, more severe bouts w1ihparesis L arm, amblvooia tinnitus ~ many loss of taste &visual field; autoosv showed 3rct n. "librocnondroma" csee T__!!Q_msen 1884) many manv chills, pain in arm&: leg in bouts; otherwise model or good health" many 3 attacks related to menstrual cycle, became more severe in recent years _Q._ many fewer aunt with periodic headaches; 3rd nerve affected only in severe attacks many fewer twin had convulsions; oatlent had dischnr2:e from Rear with sm·ere attacks manv 2 3rd nerve involved onlv in severe attacks; nact trontnJ ( 5tn n.) parestnesia several earlier bout with fever &convulsions; pain &palsy coincided; signs later abated 1889 •1 .!!!!!!Y. many mother mi1rraine; sauint orcceded oain; rniirrnine attackS abntea in recent yen rs 11 ,, ,rrn 4 mother headaches; palsy only in 4 attacks, pain alone more o ten I 1889 Flndelsen 5 5 nnin moderate &brief in first bout more severe later with vertili!:O nausea vomitin[! 1889 Joachim many 4 mother &(rl"andmother mW:rnine; oaralvsis only in severest oouts increasing with time 1889 i'.tanz many many chills, thirst, vertigo in attacks; not all bouts with motor exacerbation 1889 Vissering many manv severe bouts with oalsv, lid edema, insilnteral 5th &8th nerve deficit 1~90 Charcot several aunt insane; head pain age lG-23 and 30+; Ulree 1-m periods of daily pain ➔ palsy 11890 Pel 0 7 incinlent tabes 1891 ~lassalongo sever 1 hyperemic fundus; some attacks of headache without palsy 1891 Nason ~ fany proptosis and increased fOP during attacks; reduced vision OS 1892 Dal'~schewitsch ~ ewer at drst only a few bouts with palsy, later more frequent and more severe 11893 Borthen ~ fewer first bout 1 monLh post-trauma; but history sounds like typical migraine 1893 Oat'tticr many ~ ear1v hism llke m11!rarne; later oara1vs1s swrn~11edsides wttn oUler neural. Sll!nS 1893 Snel _ir_l___ many many lid dro: became permanent after repeated attacks I 1893 " "2 ..!!!!!.1.,V_2 onlv 2 uts mild 3rd n. oaresis with re£Ulnr mi1rraine attacks in between 1693 Knapp 2 2 first and second branches of 5th nerve involveo; only 2 ~uts, SyPnilis not rulea out 1893 Stcenhuisen_ several mother migraine; first 2 bout.s without pain; n!tcr age 6 l yenr permanent pain ...!.filt!..... Parenteau ,..1 many~I many attcks with 2astro-intestinal troubles, related to menstrual cycle 11 '' -.r~ many malaise & vomiting but no marked pan in attacKS 1895 Chabbert many many sister &cousin migraine; convulsions ns child, headache age 10-12 .... well to age 23 .... age 30 11opthalmoplegic m. 11 -,. age 62 bUat. 3rd n. palsy _.,.2-monthly bouts N3&3 .lhl!L Chiarini no ophthaimoplegiChemicraiiia ~ o~I ()"55:1~9 ..!Q__:IPP4a5d:I ()l L l-5d 7 6 years -, normal 2 2 no orcvious mi2'raine and onlv 2 oaralvtic attacks ➔ no follow-up 1895 Karplus _•_I_~ periodic oculomotor paralysis _Q_ -~-4..;!, 6m ..§.m_ ~ _..!,_ ~• 2=1 weeks In -+-paresis many many no nnin in first eolsoaes; s ills acre 11:S ➔ died trom GP: neurofibroma'' in H 3rd n. 11 1'12 + . 0 43 8 8 pP 24h + H 5-6d I 3-6 months In -+paresis ~ many knocked unconscious at age 8 ➔ first bout 6m 1atcr; some oouts wiu1 5t.n n aeliclt 189;:i i\locli - perioctica11y recurring ocu10motor palsy discussion of subiect and of own and orcvious authors' findimra and theories no new case 189.j Ormerod &. . t? recurrent _purn.l~sis_of third nerve pP days + L weeks g-lOmonths rnydriasia many fewer palsy only during severe attacks; nasal pallor of disk, lid lag on blinking I 1 1 O d'l5 llolmcs-Smccr w1U1miirrnmc ______ _ ,..1...fil!L. ciC'Schwcinit1: no recurrent ocuJomotor palsy O _Q_30~ ..!.&._~ ~ R weeks 3/w-6m _I __ n -+-parests 1896 Ahlstrom no recurrent oculomotor onralvsiB - 0"'50 47 47 + O R3 m 1 vear •-•-- ■ -==-.,.=-- ________ ~ --· ___ ..,,. --- ...-~ "'·' .......... .,...._. oormii:I ~ d'Alch~ I Ballet) ? ophthalmopieglc migraine . + a'37 8 14 ~ + R 3m + 27car I n ➔ paresls . . _ .. __________________ _ 1800 Spicer & ...!!..L_ ..::!:1. recurrent paralysis of ...:!:.0"'10 _G__ 6_ ~ + L lm + 2 year , mydriasis . , _ Ormerod •3 + ocular nerves + 0"10 8? 2.5 ~ ..:_ L 2-3d ?. .paresis . ______ . ___ ___ . . . __ 1897 Bouchenud no opht.halmoplcgic migraine O -~61 .!L_ ~ ~ + L stable each 2-3ml 2-3m I _ ~__ I many I 1 I "common ll1UZrainc11 to arre 30: nue 60 locall7.P.dhl'!ndR.P.vP nnln .....,nPrnrnnnnt n!1lc:v e_ach 1897 Charcot no oohthalmoole~ic mi~raine O . .!!_ lL_ _;iJL_ ~ J!._ L-R m + 4m-2v . . .. __________ . ---··· . _ ···-··.. _____ -·-·· _ -··· ·-···· ......... ······-· 1897 Coutouzls (abstr) - opntna1mop1cgic migraine 27 _-_ ....QE__ N 3&..4 - --1 1 normal 1897 D1Astros no mirrrainous oohthalmoo1e2:la O _Q ~ .§.Q_ _§_Q_ R=L ~ + acute ______ . _____ . _ _ ____ , .. ____ ... ---· ______--· ··- _____ ---··1897 Giebler no recurrentoculomotorpalsy - &ch ch ch nP + L lw-3m 2-3y I normal I ·--· _ .. ___ . ___ ··-··-···- --·--···-· normal 1897 Kl1atschk1n no pcriodicnll~recurringoculomot.orpalsy -~~,...!!._~..±.._~ 2w-2m ---·--•----_ . __ ----------··-···--1S9'i . 1\lingazzinl ~49 no ophthalmop eglc migraine O 6"59 53 53 pP 4d + R months 6 years . normal . . . . 1"'B88 FUrst 1888 Joachim Bernhardt recurrent paralysis of motor oculi 1·ecurl'ing ocuiomotor paralysis no periodic oculomoto,· paralysis _.:!:... recurring oculomotor palsy . PAl,SY :s >, :a Cf.l5 117 3: Period of n.ecurrence ATTACKS PAlN paresis O ~ ll...... -1..L __QE...fu!__:t_ L weeks normal O .O....lil. _7 ___ 7 _ ...Q!!Y.!_ + L 3m naresia ~ cf'55 .£h__ ..£.h._ ~ + L short n +paresis + + J:ll.1!._6_ _!Q_ __ +__ .....:!:_ L 2-3w norinnl ? periodicallycxncerbatingoculomotorpelsy O Cf'20 18? 1~ pPshort .....!.... ~ oaresis + periodic ocuJomotor paralysis + _Q_27 ll..._ ~ pP 1-2d ~ R 3w-2m normal + recurring oculomotor paralysis 7r ()"23 14 l·l pP 1-2d + n -+paresis ? recurring oculomotor paralysis O ~-9__9 ___ +__ + R lw+ 4w-5m paresis + ophthnlmoolc~ic migraine + ·t3fl JL .l.Q_ ..P!:..k_ ~ H 2d-2m ~als~ years paresis no recurring oculomotor palsy ___ ?__ ?___ O __ ___Q_3d-2m m years ? + pcrioclicophthalmoplcgic hcmicrnnia _ --1Q.11__ JUL.L..P.r..l£_ ___!_~ ? paresis ? meg;rim acc. b.v oal'alysis of 3rd nerve O 12 7 7 ~ + L ld+ 3-4 weeks n ➔ paresis + recurring oculomotor paralysis O ~ .11..._ ..,!;1__...l?E....!L + R 3d 1-3/month n +paresis + rccuning oculomotor paralysis O cf46 16 23 pP 1-2d _,!_ R 3-4d 3-4/year paresis no ophthnlmoplcgic migraine . _2.__Q_65 .£h..__.B._ ~ __Q_J..i.::ll=.R_ 2m-ly normal ....!:_ recurrent 3rd n.palsy ass. with migraine J!JJ...!Q_ M._ ..l!L._ ___:!:_ ~ 2-3 to 8w naresis + _ _Q_lB ? ? + + short palsy 4y normal no 1·ccurrent oculomotor Parru.vsis a'-tl 40 ..1.Q _ __ +__ ~ :b..1::t!_ ll months n +paresis +'? recurring oculomotor paralysis + _Q..:L _3_ __.L_ ~,__::_ L 8w pt.osis 2/y mvdriasis .:!:.1.intermittent muscular paralysis _Q__Q22 12 O + L l-2w each year normal +? . . 16 8 O ._!_ ..RJ..:.M._ every 2-3m n +paresis ? ophthalmoplegtc migraine + 0"53 11 52 pP hours + OU short every 2w paresis no + 3-5/year palsy 2. 5y off &on weekly bi-ycerly 6ro-4m 1-l months 4;:6 weeks ma- I I I "_ I I -----1 1 -::== In colu:110OJ\1?: + ...patient definitely had migrn.lne; +?•patient had probably mlgrainc; ? =-migraine questionable; no• definitely not m1gralne. ln column TER~'IS: d author spoke In discussion; foreign terms were lransllterated. In column PAIN: pP • pain preceded palsy by time indicated. In column EYE 11' 11\TERVALS: n -+paresis normal alter early bout.a but parellc after repeated attacks. Ages indicated In years unless otherwise stntc1. For all columns where usC!d: +--' observed; 0 ° absent; - not mentioned; l ~,lnfnncyi ch• childhood; d .. days; h hourSi w • weekBi m monlhs; y years; ? not clearly indicnted; R right eye; L left eye; OU • both eyes. .L .,... • ••• ., ----·- ··--·· Table 44-9 (continued) YEAR! AUTIIOR 0 M ? "'j TERMS USED TO DESClU BE CONDITION( SEX ~ AGE ~ s~I/) C, Cg ·e .c. - :.i.. ~ fb9i-j )lingazzmi II lb97 •.~~7 no 'I #.,.°a J_fil_i_:1ccmi11S_ld __ .ML,·s .. !ill_. !2Q.- micll<'ri lb9J) _Knr !us 1899 I Padcrstcin 1~99 Ti"-OcnUncf 1900 Colman I - I 1900 Lamx .l.l)QL Mobiua 1JlQL Seifert 1900 Seiffer 1900 Stirling 190Cr Ccszvi1skv 00 - j ophili p ..fil_moniei?[c ----$-- mia-roine ----~L--- • .i- -•-- ___ ,., .... i~ I+ _j_rt..:>curl'Cnl , __jj---- OCU.1uJ11vw~puuuyou, ------·--# P--ru--......,.,, ..~ piil ... + ~C~~ITc~l'l1• ~ '"'"'llf.... - .....~ ..,,1ntrn,..,,Jnmnt, !...,........... ,.......... ..,..... y 1 - •• L.L-' ---••---•-no nltcrnatin~ - ul:!uuuu.mul:!1cisu.: 1111i:snuuc t ; ~i~c palsy ·-· _____~_uJomotor -~---------· ~-.-I+ I ophthnlmopleglc ~_,, .. - .. , .... -,..-,...-•mi,•- migraine ... ~ --, JU, ophthalmoplcglc - ... h.h" -~----·-mlgrame no ophthnlmopl"'g1,.. mfo,.-a[n.-. ..0 ......~ ..,............. no ophthalmoolcl!:u; __,-'- -•~·-'-m1l!r1:1rne ---•- -·-- Ow.DJ --•--ocu1umuwr no recurrent + + 1929 ... tll N IC 193Q_ 1930 Townsend ..!J!ll_ Dnssen 1931 Gareln&Dollfus 1932 !llelschowsky .•I " " •2 ·• " •J " " " " " " E •s7 • M 21. . + ophlhalmopleglc migraine no oonwwmop,egic m,grarne no recurring pnra,ysls o, 3ro o,ou, nerves + ophthalmopleglc migraine 11 + " + " " + " " + " " + " '" Period of Recurrence EYE IN INTERVALS NU~IBER of ATTACKS zCl::I mry I many many t6l 64 64 DETAlLS ~£ :1~ >, en ~ C. oriszlnal not read in .!It 62 ch ch pP 8d + R ~w-ms :i::-3m-ly 18 i ch 2-3 d + n ::id every 2-6w ~ 138 £1._ l!..,. pP + --:;:- ~ irregular I O ...!,!_ll._ 11 3 w + L 3w 3w-ly + 26 26 26 pP + R-Lshort dally 1 ±._ 31 22 22 pl' Id + < rears _il. !Q_ 1.Q_ + ..::._ L short 4-Sweeks 1 .:!:....0""49 _8_ 1.!!_ ~ ..:!:.._~ 4-5 weeks I + &14 Qh___J.L ~ + L w-ms 1/month ....Q_ _gJL JL_ 12 oP + n 2w-ly 5-6w I JL :.i ? T.t gradual evcloomenl of oculomotor dC' _Q_ 0"23 5 ..5 li.s§_ ~ + L 4w-3d l/v-2/m + ~2 .!.Q.__J..7_ _..QE._ ...!....... ~ 1 month + 50 _7_ _J_ pP 3-4d ~ ~ 1/month _o_ I !1L __1_ + + ~ 2w-lm _g_ _8_ ...!_ 24-46 h + L 4-6w l-4tvcar - O 36 29 0 0 L lw -+ + 2 vcara + 0_18 iCh 13 oP lw + R .G-nw 2w-7ycnre ...a.. (Ji21 lch 20 ~ + L 1-2w 3·4/vear o i..!.1._7_ 7 oP 10-12d + R •a-Im 2m- 3/y + .!.L lQ__ ..lL. pP fl_fl,, I + L .. ~ w 3-4 months o 31 14 31 R weeks Gm-ebort _ Qj_g_ _8_ _L ~ .JL Jw ~+ i&iears o 0"19 8 8 oP 2d + 7::sa-2iii"" ul 1/y review of literature - no new case - i28 ;\L_ 28 + -f tt ~w ~- ,UJy A dL_ ~ ~ + ~ 2 weeks 22 ? 19 + ,0 R 6m + 2 years O l50 7 7 oP + R 3-5 d 1/month 28 23 23 R + _§_Q__ :ill__ 1.Q__ R var. + R 3.5 m ? 22 Jl_2!,_ pP 2d + R 3w 8 months O Q_37 ;l,Q_;E.._ + U R 11 week 0 ~16 6 6 pP days + R 2w ]/month o ~ 2o"" -ZO- + +'" ~ ns --nw- rn ~:1:t n-+ paresis mvdnnsls slrude enia. n -,..paresis oormal normal n -+palsy n-,.. paresis onrcsis normnl ect n -,..parcels n + palsy n .... areels n-,.. arcs is n + arcals n + ares ls norm normal paresis normal n -+oalsv normal normBJ ·r mry age 6 fall-boutsofpa!n ecchlmosls tremor vertl20 malaise Increasingly severe 11rst oout ncodache nnd vomiting for 5-6"'i 2nd oout for 6m with n 5th & 7th n.d<>rtclt fewer brother migraine; childhood ml•r. abated a•e 30 rure 35 severe bouts with oalsv mEiny common m11cra1neattacks intersocrsed with severe onrnlvtlc attnek!II 'f ➔ oculomotor nalev noocarcd after severe nnln first n and Jntcr L no ottncKS wnuc pregnant ( 11 times) paln and 011ievstarted elmultancouelv single episode or int. ophthalmoplC:R'.lo.; no clear mhtralnc: 8\lt'Ollenchc-ck, nose !;>Iced~ minor bouts without pa.lay; graduaidcvclopment orparcsla with severe pain 3w recent short R-Loaln &neuro-osvchtnt. sl1me vlelded to antl-svohll!Uc treatment 5 5 2 sisters headache; hypesthesla or N 5 1 feeble carotid and temporal pulse ~ ~ decades of ophthalmic ml~ralnc ➔ sl!Jzht otosls in attacks -+ oermanent oalsy many -~ 3 cn11nrcn have ml2:ra1.ne; trom aR:eti c1asa1cm1R:ra1ne-+ ptos1s lOQ:ethcrwlth paln ~ ----r- mower tnSane; smce c many attackS or "sick headache' "!.!.!:!!..OUt paJs_v ~ 5 manv bouts of hcmlcranin vomlU~.etc. • oaralvtlc bouta onlv aa:c 12 19 22 27 29 many ? vears recurrln2' neadache; n.mU soared nnd 15-minutc int.en-ala or normal EOM .!!!!SY. fewer irst oout t1aoost-trauma m •a t accreaae o 0U1 nerve r1.1:nct1on __ ~ many mother 2 siba mla:r. • pnUenl naa natn wilh sclntulaUng 1cotoma &ipaln togcthc_r_ ~ ~ mower m1gr,=~; oatlent had oatn ana cotncldina_sc.lnlll. latJr~. .!£.o.tome "nal ■)' .!!!.!!!l.. many I n1111cu1torccps aenvcry -+" weeKB nU'r nrst B!!R~~__ _ _ _ __ _ ~ many palsy alwre:s accomponted by bouts of._h,ur p•~n, outlutlng_ the pain __ _ 4 palsy dur ng last 4 (of 7) pregnancies~. out paln. nausea or vomTtfrig manv 7 1 sister epileptic, one "alck hcadachca@;;tnor ~~ta of migraine wil:llOul pnlay many fewer boutsof pain since chlidbood, oals o or the last few Yt'arl _ ~ fewer oouts of Intense oatn ,_a -+ 110urIvIX11'81stor minute• -+ ptosis ana am yopTa many ma mother ml ralne; sin eala to nave atartc<J after head t~auma _ manv age 14spe~s ot unSat. dim vision L Iiashes -+bllat. J)Bfn-+ constant headache 2 2 only two episodes: ltrst at age 8, second recent ___ _ sever 4 only 4 paralytlc allackll last cturlrurtv0hold lnl.<><_11"'1_ I no new case . __ _ __ norm.. ..1L_ 27 no attack during pregnancy; paresis R half-to~ and6th nerve ? many many had attacks of pain as long as she could remem r, pals last 7 years oaresls 2? 2 "n1s" for 6 m al age 7; freguenl pain In back of eyes, an~ n~slagmus N--+ narPsls ~ many flrat palsy BR:e7; squint later permanent exaccrbatlni dur ~attackB I manv ~ oaresls or 3rd, 6th and L<i::Ulnerves ln auackS, ii' ,m n. narcs csla and mlo.da .!!!..!!}L _,-__ son mUl'ralne"· heaaaches with Unnltua nausea worsenlrur rcccntlv n-+ oaresls many 2 second oaralvtle attack with slillht fever and drowsiness • m~•• ~ oatn R or L tor ·1 vears; recent oermanent coalnlese) internal ophlhalmoolcda normal mry ~ aamlttea Wltn tever & stUI neck ana nlf"i: lrom 1)\,. menlngltls n -+ myartasts . ~'I - I year amenorrhea, attacks of L headache & nausea with sclntUlalions and vasodUallon for days; later coinciding bouts or Internal ophthalmoplegla + &#5 23 25 PP 2d + L EOM 1/month oaresis many 2 mother & sister period. headaches, grcatuncle epilepsy; !OM spored in allacks + 43 1£h._.!Q_~_.:!:.._~ recurrent normal many lewer slsterm1Jtr,jc1ass1cm1R:ra1ne~1ast3y3rdn.--+ ouat, ocwaroa1s1es +died 27 17 17 --~ + R4d 1/month IOM oaresis m•rnv fewer ouau1ary sector pa.isy, acscrHN-'t: as worm-like contracttons 01 sohinctern - Q.1!.J..... ..!L ~ T L 3-6 d 1/month normal many many migraine with menslrualion, Ilral al age17 -+ J l y remission + !OM palsy - i;,>40 ch ch + + short oerlod!c n -+oaresls many ~ vague descrlptlon 4 cases none with clear ml,rralne hlstorv or recurrent pa sies general discussion + .f.Q:.,g_(..1_1...... LJ -r L ;sa .tvear normal mother "sick headache"; forceos birth; first 4 attacks without pain ? I ? I ? I 7 I pP + I 1-2w 3/year n-+ oaretle 5 5 skelchy rCJ)Orl 3 paUenls none of them ml2ralne: *1 had septic clot· #2 ? nvsterla· #3 CNS vaacu ar disease with mult!l)le ae1ects 0 IQ 15 I 8 I 9 I pP I l I L 5w-1.5y n.s. mvdr!asls manv 4 I llrst bout with L 7tn n. -+ several with 3rd n. -+ lasl ~1th aohonla &swallowln2 d 2 cues, s..,,,,awY menttonea, ot mlgrlllOO wi:n bouu, ot ocu omotor pBJsy, p1_us ~eneraJ a!scusslon; ti uou ulmmer scotoma in migraine attacks • + s ared + ed to I.e. O . ____ r-·...1 __ ol __ oculomotor ___________ ____ _ onrnlvsls nl'rvP. + . recurrent ...................oculomotor ,.,.,,,.f,......., ...i,.,_ .......n·arnlvsls ..nlm, 10 recurrent + ....................... .u.wun ..,... t' ....."'"1 no intermittent OC" -·- mu,fcJC __ ., __,_ --•~-· +? mlgwinc ~,ndW'V 190:! I Knr-nlus •I PifCIY ~, . •2 1903 de Lnp..:-rsonnc + oprlhalmoplcglc migraine 1903 nusi:,cll & cnntab + m ra nc w1u, oontnrumoolClllB 1903 SchlllinQ: + recurrent oculomotor pnra.lysls 1903 ~Vm recuri-cnt oaralvels of the third nerve 00 : Turner <!1 + pcrioc:lic oculomotor parruysls 1901 ,, " •2 + witn headache 19CH Kollarlts + ophthalmopleglc migraine : 4105 Ln(on & Vlllcmontc + cil. Lcci6zio orie-lnnl n. r, 1977 ::10:, SoUler., Posrv no recurrent ocu omotor oalsv +? recurrent tnira nerve para1ys1s 1906 Grilnbnum !~06 Jochmnnn + recurrent oc, omotor paralvsls 1906 uo,·d ophthalmoole1 le ml2"ratne 1906 Sil ? opnrnn,mopIeglc migraine 1906 Wilson --+ oohlhalmoole•lc ml~ralne 1907 Fisher •J no "o~hthalm~leglc migraine" 1907 d" Lapcrsonne + op thnlmoi{egic migraine '...litQL sHn no ophthnlmoplcgic migraine 1908 Bornstein no ophthalmoplcgtc migraine 190ti Flnlav +? recurrent£r°lsy of third nerve 1911 Bouchoud no mlnaincth oaral1·sls ol loM 1911 Shlnoya + recurrent OCU.lomotorpora1ys1s 1911 Westphal ? ophthalmic hem!cranla with 6ouls • of ouoUlarv rilrldltv 191,, Hunt ,1 ? paralyllc ••. sequclae of migraine •· ·• •2 +? " " " " 1917 A. wwenste n + recurrlna- oculomotor paralysis 1918 Hensen + hcmlcranla onnma!mlea !--1fil.L nllvAr + oohthalmoo!e,rlc mlnalne J.QgL Duane no oohms,mopIe•le mi,rrainc 1925 Stretcher ... recurrent oculomotor oaralvsls 1926 Lodze • ophthalmople~tc mlgralne 1927 de Lan:.;e no recurrcnl ooFthaJm()l)le•la 1928 R<>hmack no oontnB1moo1e,r1e murraine 1928 Ehlers + oph_lhal_mo]l_legle migraine _ 1928 ~=~----I no i-::"':ri□:=:::~~==-=;------1 1929 i..;;:.:;:."'+-----t? D A T TA C K S N . P LSY 6 pP 24h T+""l~l77m-l& ·1n -paresis 2~ nP Sd+ ·1+ -1H 5~w I l yenr I paresis + )0'"37 £!!_ 1!.!!._~..,_ ..::._ L l-2w I m!Jz7-]0d I n -+oaresls O (1'22 £..!}__ 15 ~ + ~I l-4w 111-..paresis ~ '--- ___ uf' n.·c. ---- ere -·-· -···--'mig:rn.1nc w1U1 muisc1e -·-•--~wtty '4 t:.o ~ P II OO IQ 20 6 1h27 27 - nnhthnlmnnlPule'! mlurnlnA __ ----------c·- _____ ______ 9 1901 I Stocwcr ON SE T ~ many many many many ~ 1 sever 2 !!!!!&. E!.'!!.\L !!!p.- I ---r-----ro- "° + 0 ' + + Q_26 h ~ _L <:f'27 14 9 j.!._ l.L. 32 h - Q..!L 5 - Q..!i.L - Q 32 h I• ·; ~;,... ,uo '-iii"€61B Sm • 3 rmal __ +__ 0 ~ 3 months rmal 0 0 4-6 w ? rmal pP days ...:._~ 5 weeks rmal + + .1!..l.!!!L. 2 weeks rmal P da s + ~ lrreK)!lar aresis ...Pf.l!L... "'+ 2-3/year aresls P lw "'+ ~ lrreK)!lar -+paresis + + R 3-10 weeks n -.palsy _,. ~er--"'+ .lL 16 12 .lL ch 5 .1L 17 ~~~ " - • :: ~ u... 2 months ~ ~ ~·l-.-"7~=~====r.;-~====77i=Ti=;:;--';b-;;:::;;-r;:;;;-7.,:':;-~,r:::-nvolvec! _2_ neucysm enlloncd many many 2 ma n a er many a ac I-" Ul ~ ~ Table44-9 (continued) 0 YEAH! AUTIIOH I TERM ~ 2) USED TO DESCRJOECONDITION M ? .i:: > SEX AGE ONSET ~ C: "'; ¾UJ =$ ~ Li.. - !! .!!!I ~ ~ ca ll, ATTACKS PAIN I PALSY .. Oil. ~li =QJ ~ Period of llccurrcncc EYEiN INTERVALS NUMBER of ATTACKS DETAILS ;;,• ol ~ 0. 0. 1-:: • • . i c o"io 7 io pP+ '"Tl~I irrCh'llinr I oormnli m.nny 1-1-1 recently had first attnck or oculomotor p.alsy with complete' remls'Jion I + o:,hthaimopicg1c m1g1n n - .,,..,.,....8,-,,--.-+ L G• k. I T 11 11 - u i, t. r ""Q wee s pnrrs a m2ny many patient could not re:call when ~ulQmotor deficit started -·- ____ _ <9 i1 i1al ,ul ••le miarninc O 66 Gil~ -;;p-o I R 3w 2-3 mn•••• I --••••• I pain for 7w ➔ l__-:;!_B!._ remission ➔ pain with palsy, pupil spared sugar not re29rtcd no on t ' .mo e. n:t1rrnlnc lncludil'U!' n11variants· ooinlons o!' previous nutnors nncl own theories; no new case = c~~~1 ~:~,i~\: 1~ m~ch~nism of oerlodic oculomotor orusv nnd ophthnlmop.cgtc migraine vs. nuncurysm: no new l'ASC t('D()rtl'jl_ _ _ 1 c.. . . t oohthn.Imool<'g"lR 3 cnscs with third ncrv" ,alsv nlus vnrtous other defocts· ...... "nor ,h,..... had mlgrnmc-ty~r<·& -I ~o ~~~~~:i~n or rc.'rurrcnt oohthn..lmoi>.ce:indue to Ienklmr nnrurvsm vs. oohtn:umoulcglc mlKrninc; 3 cnscs with nnn11 ...•smcz _ ... hemierania nisomotorln O cf-13 2Q...J.Q_ ..2.E...M__ + n :j-1 d JI days mydrlasls I many many relnuvclv brief nalSl' (•,ccent for punil + , n O 29 ch ch + t I L I -1-6 weeks I paresis I mnnr mnn\· mh'!'rai~_ wl_t_'!__01_mmer bco~~3:-~tncc ch; ~~ra~i-~~sy not tndlcnted . . . - . . _ summary; no new.cnse I -r _ , 0 ,htimlmoplegic nugrnin<' .!Jlil!L. BiC'Lsc:ho\\Sk\ I h h I oplcS"ic migrarne cases thnt sound like aneur •sm or otncr onrnnac aisense up unucr I.he nssum >tion of ''nC'uru-vl'oetat1\·e" aoomal\· or nsvchorrcnic orirrln ,:1 110 0 l!J-lO D:tllr P ~h~i:~~oplegicmigraine 19 31 19 19 nP I:. h I+ I It lw Ii vcars + I ·1 J a I naticnt dinbl'lic· attacks _Involved 7lh nerve, lth nerve, R 3rd nerve L 3rd n. 0 1 l9-lO Elllotl no P \ ' 1 0 legic migraine S sketchil\' described cases none with third nerve dcfc-ct; #l hnd 6th n· #2 n cztnal bo•Jt c:-.ch or 3rd &6th·• 3 & -t lnfl:-.mmnton· disease·.., '.';-f) lntracrnnlal aneurysm~ 110 1 1 !1t!..l.._ BU1:ki . , ~~l~tl~~~~ ~,e~ic mi~raine _Q_!L _i;L 1!L ~ ..J_ l.!..!!!..__ month I norma _1_ 2 I hypcrtc>nslvc with ''mlgrnlne headaches" for ~r, two pnrcuc bouts 1.:; vear apart 1 1911 llnilO\\l ~ + (/18 Om 9m 2 dnys + L 2-~ cl every 15 d I n -+ parcels many man? I mh!ralne & "bilious headache II In ramilv; 1>nindid not orecc:>dcr>als, 11th: 111'loplcgic migTnlnc lllL \'i:t\lE>font6.Chnptnl + op hn . 1111 . 1. 'nc:> _ Q 13 Gm Gm ? ? --,/-G months I n ➔ paresis ? ,-case incomnictclvrlescrfl>e-n l'Mit sounrfslike rniurain..:- history 1 I!) l l llcr:nann & Hall ..1 ... opht nl,~lop e~w ~ m -:- 13 2G -l l I B.or L with curller non-unr:tlvlic attn.ck mnnv 3 miurninc familv · since nrre 26 Hor L naln ➔ nnosmln & rhlnorrhcn: soh. mucocoele . .'' " •:? no rccunent third ner\'C pnlsr snw untlent with 30 nttncks and I normnl nrwrlograms no sl~n of nn!los nsm· snw "half dozcnd or so" such cases deflnitch" not aneun•sm lQJ.L J.cflerson h h I1 l - ()"63 1G JG .. + H l d:iv I-i month.s n ➔ pores ts mnnv m::in~':llx>uts .of·c·lassie mlgrninr became milder with age; 3 & Ith nc:>I"'\'(' pal.s1.· p<'.rmnnt"nt 11igr,une • l2ilL KC'nned,· • oph~I~l 1~~~ 1 \~t:~~ n~lg, ~ilw o Cf2~ Ti Pcinvs + ~ ? ? ___,,- _?_ sketchy description of i}atlcnt with bilateral head pain H)l7 HOt:jCI'& 11, nn opl; ( Pl g ' c o O"IG 3-3~P 4~ h + ~I I/month mydrlnsls many fc,ver t?tosis only in severe migraine 3ttncks 1 ~ FB \~q)sh ~µ t l~ mop cgic mi,7riun + lrii'i 7 ~ ~ + t I H 3&.Gn I I ,week I unrc>sls manv fewer brothc_r~&,:hUdren headaches; age 15-17 inte1·mittent diplopla; ng~ 31+_~1_.6th&;_,tosis n: . t •'th, cur\'sm of the nosl<'rior communicatimr nrtcrv had hn rl •ht-sided h£_ndachc nausea & vomltln 2 for mnnv •cnrs thou1rht tvntcal mlrrrninc ➔ dil'd of ru 1turcd aneu11·sm 19~O .\lperb & SchlC'7lllJ{C'l' - - ~~ht11a:i'1~:~ ~~1 ic ·~1i ,rninc • discussion of mech:1nism i no new rnsc____ -. -.. I rficl nn1 Ml jnv_c'hccn c---- wnr'"' -1-rn.1n,. . -I 19 0 1 ~ Don~l_uc no 0 ,hth:ilmoplc:>gic mi~i·ninc iiwrcdiblC' nonsense:> nl>out 7 cases none t)('nodll' nnd none with mhtrninC' hlstorv h'Jt with fever nroteln & cells m CSF. 3rd &:6th nalsv r("("urnn1:1afwr mont~s or rears 1 :mil~los_ k ,. 1 .. 0 1>hth:ilmo~le~lcmigrarnc + ~;;6 31153 li>PG-~cll+ I Ll-JCI JrC'L.rulnr I normal. mnn"llfewcrlmothe1·mi"'r.-"nin&•1nls,·sh1ftNIJl-+L· 2norm:llrtrteriol':rrtms 2.,·n_p_a_r_t 1 !Jµ..!.... .\1B.<'l!S&"'i.~~ + I " g • _ 23 recuiTcnt headaches with utosis dio!oola and nn·drlnsts, died died of int. carolid occlusion brourrht on b\· nrtcriOPram. a•Jtons,· sho,\~ no ancun·sm -. . Bo 1 no lilt '3C3\'C'J'll0l1S aneUl'\'Slll '..12 ch 13U I pl' I+ I H S11.>l't I ? I nor~al I mnnv I man\· I WOl'SCning, with N j -+ 3Ll involvemen·: Jorge aneu1,·sm mldd.e rossa I ~~~:: :( 1'.~~t I\: ~ ~~l ks PO opl:thnlmop~ migrninc _ ()":;;; ,vith Inr!!c brain tumor hnd 6 months history of p:lrOX) smal hcad:iche -+ dlnlonia dininess ncurol ._shms with hc-~ddown: autous~ showed uncal herniation 1 ~'l . ~nglQ.ll __ oc __ .:.? ophth~lmoplegic migrnilw _ ;;3 13 :;3 • • J{-L ws 11y<.•:tr nor~u-~mnnt many high DP; ptosis nor L \\ith "anglon_eurottc" lid edema 0:1 same sid<.• . 1 19 1 + ophthnlmoplC'gic migraine .....!:.. 12 __?_ I Im pP Jd _:_ H 1-t, w 1/ ~ n -..p~rc.•s1s J.Q.:.!l 10-11 both o:tre?ts. z:iie:rninc; at fir.it. no ;>am and pupil spared; 4 normal artc:>r1ogr:ims 19~:-., \'~:.z~~up;ghen 1 w-=-- ~. 1 9011 1---+ ophthnlmoplep,k mlgrninc _ '.10 ch ch ~ t ~ . n + pals) mnn~, man\' typical m1g1·nrncfrom childho_"Jd;later amcltorated with nge 11 .i., .. •. , .. " Q 1--l 1~ 12 ~ ~ I. short 1/mon·h n ➔-pnrc.;ls 10 _I_O_ recov_~ry of oculomotor control less complete \\'ith recurring !lttncks Lincolf 6.·Cog:rn ..~ -:- ophthalmop~egic mi~raTt1c _..:.. 9.1.L_l__ J...!_ ~ ....:.__L__ ~ 1/)'car normal mnm· 1 3rd ncrvc_normn1 aftC'r nn1:nlytic c~lsode " • •9 " r Q-l .2 2 nP + L ,,J Im 1-~/vcnr nol'mnl _ a ;J mother mi"r. • normal n1111ol!rnm·,> \' follow-uri with mild t>->utsI--x,ycnr 1 10.· 7 OstfC'ld & \\'olff .,. ophthnlmoplcgic migraine in 3 naticnts administered intravenous 1~radre~rnlinc an<lonticnts rcc:ninecl normnl _:Jr~nerve functions ~ithin 7C-90 minutes· l nnlient had 30 bJuts in :.o,·ears 1 ,9GO :\loner& \'nn·IC'l'li<.'lcl no peri0<.lic mi~Tninous hNtdn<'hc> - hntl G onticnts with nncurvHm nncl 3 with nn!.!1omntousnrnllormntlons _who hn~I o~nochc hcndnchcs of mi 0 rnlnc t\·nc . _ ., ~ ICl61J ,JP \\'nlsh & .,I , ophlhnlmoplcgil' mlg1·n111c _:_1,c1_~:.1 ...£.!!_~ ~ .±.,_Ji1...!!L__ I/month In +paresis J.!U:!.!!L_ __1__ migraine fnmik; 2 pnrnlytlc bouts: H :'\3+--1+6+,jl➔ L ~3'4+0+.,I: nrll'riogrnm o· DohcrtY •~ " " __ _:_I~ _!2_ ~ J?P ~_ct _ _.!:.._ I. I m 3-ti months I normal I mnny fewer nrtcrio.,.r:im sh-,wc<I "sutr"'CStion or constriction o(lin11·ecrnnlaH carotid" .. •:3 ... - ..-- ? 1.) 12 12 t O 2 d:1v8 I months I normnl I !) U houts of unilaL. he:ulncht~& iciuint thol~ht to be In\'n,thcnin but l\!'OSt!O"minPfniled 11oo I Fl'iedm:i.n ~ .ii. .. ophthnlmop!c.•gic migraine' --no in•Jivi<lual cnse l'Cport.":i;pntiC'nts follow1.><lI-J:, y; -iO"J~; onsC'lol migraine 6x !)('Jore nge I 0, 2:'I.at 17 &• Ix at:lO: most had establisherJ migrnine pnttern \.x>forr p:irn1:..H'i:! •• " lytic attacks: pain preceded pnl&y by 2-'I d & mmally abatcxl wht•n palsy starl.C'd; palsy mostly in scvC'rc attacks (up to :!Ox); nll had 3rd and one Gth nen·<' dC'fiCit; p:llsy " -:- --.." "--faded after 1d-6w; j times pnresis beta me pcrmanC'nt (~ only mydrinsis ); :J hnd migraine family history; norm:il trsts: 6x carotid nrteriogrruns, ix sh't!JI X-rnys, .. .. _ •• " Ix lumbar ouncturc. 2x :iir cncc·ohnlo1,ram •Ix EEG; EEG showed :!x ipsilntC'ral and Ix crossed foc:ll ch:inrrcs; J basilar nl'lC'riorrrnm showed n::tlTO\\'ed :irtC'IT lQQl__ R~i!!<.·ckt· no migraine S\'nllJloms ___ _.Q_ _(}·~3 ..;]_ ~:i I classicallmi11rainc_houts abatPd in mcnooausc 4 nt:111\'_I_ classic migr. signs➔ intracranial hemorrhage: \·nscular malformations s~ 19G2 ~lacbnlch&Huskin ro recurrent ocu omotor \>tu·esis O O"GO -1 7 .,7 I pP Id _ 0 I H 1-l d I I/vc:.ir I nonn:il _I :J :1 EOM snared; artcriotTram sho,vcd :-nrotid-basilor anastomosis 196:1 S,:~n & \Jaunt__ ..!!£...in~rncraninl :incurYsm - 2 or 7 inlrac:linoitl aml (i of Gsuprncl1no1<l uncun•sms t·:iusec.ll!~ l4 j:C'nrs migraine-like- hradnc-hc atl:tc:ks ___ 1 19UI Bid.:c:>rstnff .,. ophlhnlmoplrgic migrainl• - 11 patil.'nts; onS('l in ts at nge :--,-11, and at 1~-17 in :t; nrtt.•rinl,{r:1111s Hhv\~tinctly in I and IC'ss so in •I constdction or th<' lumen ,Jf thl.• internal carotid 10 or ___ lwlow th(' cave.•rnousfiinus: 2x bilateral art<'riol4"ram .showt'<Ithis on thC' had sidC' only; :rncl repeat artC'riogrnms aft<'r rr,·ovcry were normal l9(H GrN•n, llackNt _-_I~ .., oculomotor nerve pnlsr - _QGO=ij• ~ _gL_ __ ~ ? n-+ pnrcai1, _? __ H_ ''historv of tvnical miornin.:-" ➔ s uaralvtic attacks in 21 r<.':u·s " & Schlc·zing::-r 11:! + .. 2 nmoni 130 ha~ migraine) - fr--$..-~ ...l!E__ + H :1 m ? normal m:uw fewer unilat. pain with scintillating scotoma; pu1>ilsparerf; local edcm:1 1001 \"nn Pc.'lt&Antlprmnnn + oph.thalmop~cgic m~grn~nc + _:o-rr- 3m :.Im ...l!E__ ...:_ H 2:J - lw ...:!_-'.> months n .+ mydrinsis many ~ 1~1othcr, grandmother, great.nunt mi_grninl•; firi::>t :! bouts no pain b:ll \'Omiting 1001 Pin~•us & Oaroff _Jl2 ..2J?l!th'.llmoµlcglcm1grmn~ ___ + ·()"'47 .7"!r"-a-rn.P 7d _ + TI ~year J normal___ 8-10 I lather ml11 rainC'· ccnll·n.l scotoma 1>1-otcinin CSF: X-nl_.\' showC'cisphcnoid nrntoc·Oelc l9G6 BIC'nd& Bull n:, artcriovenous malformat10ns - l!:! nat1cnt8 with un~ateral heac pain! ahm~t lw o t cmh:icl_ r<'c~rre_nt oculomot.or paralvsis; attacks in a.11W('r<' unilnw,·nl and without nura 1970 ~~E~l_l~;\lanignud - recurrent oculomotor paralysis -I l!Cncrn.\ 8urvcv of <lirlt'rcnt causC's, rncludmg ophthalmoJicl!IC' miL•Tarnr· 1970 Sac:ks •2•1 + ophthalmop~cgic nHgrnrnc ____ __: Sf.:~ 1 en 11 ~ ...!:_~ irrc~ mydriatiiS m:rnv ;J :1 bouts with l}!ihw followinrrn seriNI ofc .,..8c,.,nclo,n·g, ( bo . . .· . i 1 11 11 .. 73 + " r~-y3~.,'l t wv ·> '> -------~•---D. 1 ...... 11nneus,_nngIog1nmno101n 1 1h"~~nu1ossi~ m!~rriinl'srncl'~ 1972 Bell & :\lcCormick + ophthalmoplcgic m1g:rn111e - -(1';).:J !Im I~ l)P ~d ;~;nw \ J VC.al'S llOl'l;ia1 -m~ltlY th 1~72 ~h & c~.awln ~ oph a~,moplc'(ic mlfirmnc ___ 9~1...R. .!.L ~U + l_l__1_d__ i~t~!.!.!..h..___ pa~rs~~ mnn.v mnny first attack nft~r fall; ~11gl~2rnn~1~~1~nl~pcrm~n~~t ml'driasls and ptosts· -8 18 . . .. , lO ? ____ .-! -,. .Q_ ~ ~ . ..J!!!.~.5' _ l<.'~8U1nn 10 no nauscaorvomlti1U!OI' fnmllv htstol"\';l'llloi snnrcrf; somctlincs awoke rrom ontn 1974 ~~dclson&L€Y.) .lf3 • trans~ent benign unllat. pup11larj (.J._. _,J ~ '"2:J pl WC'C'l<s O L Id .,. months no1m,li I :! mother clnsaic migraine: patient h:id htSLOry of intel'mittcnt unllntC'l'lli hcndncfll'; dilation n1·wriog1arn normnl, first attnck without nnd second .v1lh pain 1 1i1i:i?"'" Bicischowsky " 19~2 KonBtnm Io;i~ lliley , 1933 Drnm\\Cll 1934 vnn Bogaert L9.?,LBrn?rn·;n 3 ~.; ~ P~? •8 :f;~:~ i = o n n 0 -r:r- ~J,?° : .% . -. ;~o rn t 8 -=- Im7 :I~ + i ~~cf ~ + I ~ob~~~~l~~r~~~~:~:~~ ~,~~a~~~(II~~; t,~ 44. Vascular Conditions the motor deficit will take from only days to many week to clear, though improvement usually begins within the next week or so. "Ophthalmoplegic migraine" differs from the cla sic migraine pattern in several respects. (1) There is less of a hereditary trend: only twentyfive of the patients with definite "ophthalmoplegic migraine" (marked with a plus sign in Table 44-9) had one or more relatives with migraine, and for twentyseven the family history was negative. In the remaining fifty-three case reports the subject was not mentioned. (2) There is no preponderance of women: among eighty-six patients with definite "ophthalmoplegic migraine" for whom the information was given, fortytwo were men and forty-four women. (3) The headaches or "bilious attacks" 5 begin early: most patients have had painful attacks from childhood, and some in infancy. (4) The condition is unilateral: the headaches were strictly one-sided, and during a given attack the pain and motor loss were always on the same side. Only in a few cases did succeeding attacks shift from one side to the other. (5) Typically there is no aura: teichopsia or fortification scotomata or other paroxysmal pre-headache signs were uncommon, though occasionally they did occur. Instead, the headache preceded the oculomotor defect by many hours, and up to days; and most authors noted especially that the lid began to droop and the eye muscles became paretic only after the headache had abated. (6) The paralysis outlasts the pain: the motor deficit faded from several days to weeks after the pain ended. While there was, as a rule, full remission between early attacks of ophthalmoplegia, recovery became less and less complete with repeated attacks, so that in time at least partial motor deficit tended to become permanent. 15 t / The pupil appears to be especially pron~ to involv~ment. We know of no case with the pupil spare?; tn contrast, mydriasis very often was the sole r~s,dual motor ign during pain-free intervals, at least durmg the early years of the patient's illne s. (b) Terminology The names us~d for this_ condition caused confusion because at first tt was belteved that there was a fundamental difference between the "purely periodic" syndrome, with full recovery be_tween attacks, and "periodically exacerbating" cases with permanent oculomotor impairment: the "purely periodic" attac~s were considered "functional," 6 but a permanent orgamc lesion had to be assumed in "periodically exacerbating" case . It took some years before it became evident that the two kinds of syndrome were merely stages in the natural history of the disease process. During the 1880s it was recognized that these periodic oculomotor palsies could occur as part of headache attacks closely resembling migraine; and Charcot coined the term ophthalmoplegic migraine, stressing that the pain was an essential ingredient of the condition and assuming the motor deficit to be "functional." Many authors resisted this name, first, because permanent motor deficit tended to develop in time-and thus the condition could not be "functional"-and second, because cases with repeated attacks of the same pattern had come to autopsy, and in these organic damage to the third nerve had been found (see below). These authors continued to use terms like periodic oculomotor paresis, or recurring third nerve palsy. Others however, adopted the elegant term ophthalmoplegic migraine and unfortunately used it freely, not only for genuine cases of 5. Term used in the earlier literature, especially in England. 6. Term u ed for non-organic, p ychoneurotic, or psychiatric. Figure 44- . Duration of intervals between migraine attacks reported by authors listed in Table 44-9. Most of these reports referred to intervals between migraine attack , but some authors gave only information on timing of ophthalmoplegic attacks; and in a few cases it was not clear which kind of attack was meant. (From I.E. Loewenfeld, in Neuro-Ophthalmology, J.S. Glaser, Ed. [St. Louis: C.V. Mosby, .1980],Vol. JO) T T T 101 I t TT £ T ~ 5T ~ I T 0 T ~ ~ ~ ~ ~ I ~o~~~~~~~~~~~~+~~~~~"~~~~~~~~~~~~----r0 5 10 15 20 DURATION OF INTERVALS IN WEEKS 1531 25 ➔ 30 35 40 45 50 1 year more than 1 year 1532 / V. Pupillary Pathology: Pupillary Signs in Various Diseases Table 44-10. "Ophthalmoplegic migraine" and "recurrent third nerve paralysis" cor-..'DITION OF PATIENTS 1, Definitely migraine migraine 3. Probably not migraine not migraine TOTALS Table 44-11. 31 74 18 7 11 8 4 4 88 45 43 219 87 132 Anatomic findings in patients with recurrent third nerve palsy YEAR AUTHOR 1860 1884 1887 Fournier iubler! omsen Richter 1885 Weiss 1895 Karplus 1911 Shinoya FINDINGS third nerve at base thickened and embedded in a white, fibrous mass, with adhesions in the neighborhood, up to optic chiasm fibrochondroma" in third nerve at its point greyish, club-shaped of entry into the (cavernous sinus) dura: tumor infiltration between nerve fibers; no nuclear or eye muscle defect oculomotor nerve greyish and flattened, with many poppyseedlike tubercular granulations infiltrating the nerve root, causing a wart-like swelling; fatty degeneration of eye muscles supplied by this nerve "neurofibroma" of about 1/2 pea size, engulfing third nerve, with nerve fibers spread apart and intertwined with tumor tissue; marked peripheral and slight retrograde nerve fiber loss; no nuclear defect thickened, injected oculomotor root; nerve covered by pus and fibrinous exudate, and swollen to 5x normal size where it squeezed between the posterior cerebral and superior cerebellar arteries; thickened portion was infiltrated by fibrous connective tissue with these fibers penetrated between nerve few cells C'fibroma"); fibers, separating them; some thinning and fragmentation of myelin sheaths and loss of axon fibers Note: In Alpers & Yaskin's case (1951) no pathology migraine-like headaches with oculomotor deficit but for quite different conditions, as long as pain and ophthalmoplegia coincided. This confused the picture further. When analyzed with the benefit of hindsight, it can be seen that numerous cases with true "ophthalmoplegic migraine"-as defined above-were called "recurrent oculomotor palsy," or the reverse (Table 44-10). This is unfortunate because discussions about the mechanism of the condition were often based on cases grouped according to the terms given by previous authors rather than according to their true nature, as evident from the details of case reports. (c) Mechanism, cance TERM USED TO DESCRIBE CONDITION "Recurrent third "Ophthalmoplegic nerve palsy" migraine" 105 2. Probably 4. Definitely NUMBER of patients Location, and Clinical Signifi- Kennedy: "You mean this man has had an aneurysm since age 16?" Merritt: " ... it seems likely that he has a fixed lesion to explain his third nerve palsy." Kennedy: "He has had attacks of undoubted migraine since age 16. Do you contend he has an aneurysm? Dr. Riley said arteriosclerosis." at all was found at autopsy. "I did not say that." Riley: Kennedy: "That is just talking around the subject instead of at it. Here is a man with typical migraine since age 16, with attacks each month for 1 day; he vomits; he sees double; and he goes on seeing double after each attack until he finally has a paralysis. I do not know why one should not call it ophthalmoplegic migraine. Charcot did, and he was good enough." Globus: "Why do you object to aneurysm?" Kennedy: "I think a sensible man works his life on probabilities, not possibilities. "Possibilities" are lawyer's words. It is most unlikely that this man has had an aneurysm all his life-and leaking each month or so; he is in very good health and there is no sign of an aneurysm; as he has grown older his periodic headaches have almost ceased, so I believe my migraine theory is correct." Globus: "Suppose I say an aneurysm is probable since he manifests clinical evidence favoring aneurysm?" 44. Vascular Conditions Kennedy: "He is a permanent employee of Bellevue, and when he comes to go to the throne of God, we will let you know." (From a discussion of F. Kennedy's paper, 1946, in which H.A. Riley, H.H. Merritt, and J.H. Globus contended that the cause of the oculomotor paralysis of Kennedy's patient was likely to be aneurysm. The error in this argument was not the insistence that there was an organic lesion but the assumption that this ruled out migraine: repeated migrainous insults lead to permanent defects.) We do not know whether Dr. Kennedy ever gave his promised report. The discussion illustrates how controversial the subject of "ophthalmoplegic migraine" remained throughout the years. Two questions must be answered in such cases: where is the lesion, and how is it brought about? (1) Location-At first it was suggested that the damage was located in the brainstem, affecting the oculomotor nucleus by inflammation with congestion or hemorrhage, or by a "paroxysmal neurosis." Involvement of the fifth nerve nucleus would explain the pain; and when the migrainous "nerve storm" spread to other brainstem nuclei, especially the vagus nucleus, nausea, vomiting, and other autonomic signs would result (Hasner, 1883; M6bius, 1884; Pfluger, 1885; Parinaud and Marie, 1888; Furst, 1888; Pel, 1890; Nason, 1891; Chabbert, 1895, 1911; Leclezio, 1905; Hinde, 1918; Tikhomirov, 1935). Experience taught, however, that the oculomotor deficit was almost always unilateral, and it affected all muscles innervated by the third nerve. This could not result from a nuclear lesion because each third nerve nucleus supplied muscles of the heterolateral as well as of the homolateral eye. Further, the ipsilateral sixth, fourth or ophthalmic fifth nerves were sometimes paralyzed as well, and this combination of defects pointed to extracerebral impairment of these cranial nerves. Besides, a brainstem lesion large enough to bring about such marked oculomotor impariment would be expected to injure neighboring structures as well, but these patients did not develop controlateral hemiplegia or, in fact, any other sensory or motor loss (Manz, 1885; Wadsworth, 1887; Joachim, 1888; Charcot, 1892; Darkschewitsch, 1892; Darquier, 1893; Knapp, 1895; Karplus, 1895; Holmes-Spicer and Ormerod, 1896; and many later authors). These arguments gained strong support from anatomic findings: all cases that came to autopsy had lesions involving the third nerve at the base (Table 44-11). (2) Nature of the Lesion-Although there was no longer a doubt that the third nerve lesion must be located in the efferent nerve stem, it remained to be explained just how it was produced. Different theories have been proposed about the nature of the disease process. Infectious (inflammatory) or toxic lesions: Kljatschkin (1897), Mingazzini (1897), and others thought of an / 1533 "infectious neuritis" or basal pachymeningitis. Especially when located near the sphenoid ridg~, such processes could involve the cranial nerves passmg through the superior orbital fissure; and recurrent bouts of ophthalmoplegia with pain could indeed be produc~d by a sphenoid mucocoele (Hermann and Hall, 1944; Pmcus and Daroff, 1964) as well as in the Tolosa-Hunt and other superior orbital fissure syndromes. However, the cour e of these conditions certainly differed from that of "ophthalmoplegic migraine." Others noted that patient with migraine commonly had allergies; and that severe attacks in some of the patients were related to the menstrual cycle or to pregnancy. Some lcind of autointoxication or endocrine dysbalance was thus suspected (Bernhardt, 1889; Vissering, 1889; Sym, 1903; Dani , I 920; Biirlci, 1941). But whereas such a mechanism might indeed have been a part of the migrainous di ease process, it failed to explain how the third nerve on one side was damaged. Space-consuming lesions: Slow-growing tumors were suggested as the cause of the oculomotor deficit (Leszynsky, 1901; Karplus, 1902; Shionoya, 1911; and others). After all, the few autop ies available of patients with migraine-like episodes and associated oculomotor deficit all had shown neoplastic lesions affecting the third nerve (Table 44-11). These authors explained the intermittent course of the condition by suggesting that the mass could grow or swell intermittently; or that edema of the brain during migrainou attack could press the tumor against the unyielding base, catching the third nerve in between. Joachim (1906) and Shionoya ( 1911) thought that a slow-growing mass could bring about chronic irritation with accumulation of noxiou substances and intermittent "explosions." Harrington and Flocks (1953) found evidence of herniation of the hippocampal gyrus through the tentorial gap in a patient who soon died from a metastatic fronto-temporal carcinoma, with episodes of unilateral headache and oculomotor palsy shortly before death; and they proposed that "ophthalmoplegic migraine" was caused by periodic cerebral edema resulting in uncal herniation and consequent pressure on the oculomotor nerve. Kennedy (1946) assumed localized intracranial edema, probably based on allergy, with pressure "by accumulation of fluid at the base." But Charcot and many later authors said the published cases with tumors differed from patients with "ophthalmoplegic migraine": their clinical signs merely mimicked migraine attacks. In fact, these growths-with the exception of Weiss's case (1885) with tubercular infiltration of the third nerve and only symptomatic migraine-were fibrou swellings of connective tissue. These were more likely the secondary consequence than the cause of the condition: repeated insults to the nerve by pressure from a swollen artery during migrainous 1534 Table 44-12. YEAR Vascular mechanism of oculomotor impairment in "ophthalmoplegic migraine" AUTHOR 1 85 1891 1892 1893 1894 1896 1 97 1900 1911 1914 1918 1928 1929 1929 1930 1932 1933 Manz 1935 1936 1940 1941 1942 1951 1954 1954 1955 1957 1960 1961 1962 1963 1964 1969 1972 Tikhomirov Bielschows~ Daily Bllrki Viallefont &Chaetal Aleers &Yaskin Herzau Rem~ Ver Brugghen Ostfeld & Wolff Walsh & 0' Doher!,y Friedman & al Q'Connor Wolff Bickerstaff Walsh & Hoyt Bell & McCormick 1972 \ V. Pupillary Pathology: Pupillary Signs in Various Diseases Nason Charcot Darguier Knaee d'Alch~ D'Astros Seiffer Bouchoud Flatau Hensen Ehlers Mackay Pakzody Ch 'e!!S: Konstam Bramwell Friedman MECHANISM circulatoE,Y defect with com2ression of 3rd nerve near eost. cerebral and sue. cerebellar arteries ischemia of oculomotor nucleus ischemia with endarteritis after vasoseastic eeisodes, affecting oculomotor nucleus agreed with Charcot on circulatoE,Y deficienci vascular damage, inflammatory or edematous, involving basal third nerve root vasos12asm with ischemic enctarteritis (atter Charcot} ischemic neuro12athy of oculomotor nucleus or nerve circulatoE,Y defect of nuclear area or third nerve roots (eerhaes auto-intoxication} vasoseasm in nuclear area vasoseasm resulting in "nutritional defect" circulatory disturbance resultil}g in eressure on nucleus or efferent nerve 12ressure of dilated eost. cerebral arteE,Y where it runs close to 3rd nerve or is hooked around it vasomotor defect or local edema vasomotor mechanism vasomotor earal_}'.sis with vascular distension and compression of tnird nerve possibly vascular lesion temporary d1stens10n of post. cerebral artery due to vasomotor change, with palsy due to pressure if artery runs in abnormally close association with the third nerve nuclear hemorrhage, or spasm of post. cerebral artery, perhaps with edema in area of 3rd n. roots vasomotor mechanism angioneurotic condition of eosterior cerebral arteE,Y on esichogenic basis (!) vasoseastic condition resulting in ischemia, due to "labile vegetative eguilibrium' 1 agree with Charcot that vasomotor disturbance is the essential factor vascular disturbance resulting in reeeated eressure upon 3rd nerve b_}'. dilated vessels angioneurotic edema eressure b_}'.swollen eosterior cerebral artery upon the third nerve pressure by edematous artery pressure by edematous, dilated arterial walls: prompt relief by intravenous nor-adrenalme pressure upon 3rd nerve by edematous carotid artery in the cavernous sinus eressure ueon 3rd nerve by neighboring dilated, edematous artery {basilar system) vasoconstriction with edema 1 obstruction or hemorrliage eressure on 3rd nerve by dilated, edematous carotio artery eressure of edematous carotio artery upon 3rd nerve m cavernous smus comeression of 3rd nerve or embarrassment of its blood sueelr hr dilated, edematous carotid a. compression of 3rd nerve or interference with vasa nervorum either by swollen, edematous carotid in cavernous sinus 1 or comeression between dilated post. cerebral and sup. cerebell.art. vasocons triction followed by dilation with pressure upon 3rd nerve CAROTID A. I \ m J Bl '21 I st '2: Figure 44-9. Possible mechanism of ophthalmoplegic migraine. A dilated, swollen carotid artery would impinge upon neighboring cranial nerves in the cavernous sinus (the oculomotor, trochlcar, abducens, and trigeminal branches). (From J.P. Walsh and D.S. O'Doherly, Neurology, Minneap., 10 [1960]: 1079) 44. Vascular Conditions attacks could be expected to bring about such proliferation of fibrous tissue. Vascular lesion: this type of injury was considered as early as 1885 by Manz (Table 44-12). And as the events of the attacks became better known, the theory was found to account well for some of the features of "ophthalmoplegic migraine" that would be difficult to explain otherwise: -Why do most patients with "ophthalmoplegic migraine" have no visual aura (although some of them do)? -Why does the pain in "ophthalmoplegic migraine" always precede the palsy rather than accompany it or follow it, as is the case in patients with aneurysm? -Why do these patients have a mixture of a few severe headache attacks with ophthalmoplegia and frequent, regular bouts without motor defects? -Why are there complete remissions of the oculomotor loss after early ophthalmoplegic attacks, whereas later at least some motor deficit tends to become permanent? -Why is there usually no "misdirection dyskinesia" in "ophthalmoplegic migraine"-at least during the early period with full recovery between attacks-as there is in patients with ophthalmoplegia resulting from trauma or aneurysms? As already mentioned, the visual aura in the first phase of the classic migraine attack is thought to result from ischemia in the occipital cortex, caused by vasoconstrietion and consequently reduced blood flow in the basilar or posterior cerebral arteries. In other patients the carotid artery may be the main seat of the trouble, and no visual aura will occur. The third nerve could be affected at either of these anatomic sites in patients with the arteries running unusually close to the nerve: rostrally the carotid artery could compress the nerve in the cavernous sinus, together with the fourth, sixth, or ophthalmic fifth nerves Figure 44-9; or the third nerve alone could be compressed near the bifurcation of the carotid and the posterior communicating arteries. Caudally the posterior cerebral artery is hooked across the third nerve and may press upon the nerve near its origin from the midbrain. The migrainous headache is assumed to develop when the vascular spasm yields to vasodilation with edema of the vessel wall. Obviously, the third nerve would not be involved until the vascular swelling neared its peak; and while the artery would exert pressure upon the nerve the pain would begin to abate because the active period of vascular swelling had ended. Arterial swelling sufficiently marked to cause ophthalmoplegia could be expected to happen only in severe attacks, whereas minor bouts with only moderate vascular enlargement would cause pain but leave the third nerve untouched. The rapid onset and short duration of the motor defects, and the special vulnerability of the pupil fibers, I 153 5 would be expected as results of short-lasting pressu~e upon the nerve; and with repeated episodes of_ this nature the development of increasingly severe residual deficit during the pain-free intervals would ~ot _b~ surprising. Finally, marked "misdirection dys_kmesta would be unlikely to occur in a condition resulting from repeated short episodes of pressure without (at first) gross disruption of the nerve fibers. 7 Arteriographic evidence has been presented to support this theory: Walsh and O'Doherty (1960) and Bickerstaff (1964) found narrowing of the lu~en o~ the intra-cavernous segment of the carotid artery m patients with "ophthalmoplegic migraine" attack • and Friedman and associates (1961) observed similar segmental narrowing of the basilar artery between the origin of ~he posterior cerebral and the superior cerebe_llar arten_es. Moreover, bilateral arteriograms showed this on the 1de of the palsy only, and arteriograms repeated after recovery from the attack were normal on both sides. The narrowing thus was considered a result of transient edema of the vessel wall. Local ischemia, brought about by migrainous vasoconstriction, has been suggested as another vascular mechanism for the ophthalmoplegic episode . Charcot and other early authors spoke of post-ischemic endarteriti in the area of the oculomotor nucleu (Table 44-12). This assumption was dropped when it had become clear that the damage affected the nerve fibers in their extracerebral efferent course. Moreover, the va o pasm associated with migraine attack preceded the development of the ophthalmoplegia by many hours or days. However, it could be argued that edema of the ve sel wall of large arteries may hinder blood flow in the small arterial twigs of the vasa nervorum of the oculomotor nerve. This would be compatible with the late onset of ophthalmoplegia (at the peak of arterial swelling) and with the short duration of the motor defect. Ostfeld and Wolff (1957) injected solutions of noradrenaline intravenously in three patients early in ophthalmoplegic attacks, and two of them regained almost normal motor control within 70 to 90 minutes. Since such injections would be expected to constrict small blood vessels at lea t as much as large ones, relief of local ischemia appears a less likely mechanism than relief from pressure on the nerve by shrinking of the arterial trunk. This would agree with the vulnerability of the pupil fibers which are spared in ischemic third nerve palsy reuslting from diabetes. However, noradrenaline also raises the systemic blood pressure and reduces edema; thus con- 7. Recently patients with "ophthalmoplegic migraine" were described who showed subtle signs of ocular "misdirection," especially slight lid retraction on downward gaze, without ever having had a period of prolonged ophthalmoplegia. It appears natural that repeated, short episodes of pre sure would each give rise to interruption of a few of the nerve fibers, with consequent slight dyskinetic signs; and if looked for actively, this probably would be found more often. 1536 / V. Pupillary Pathology: Pupillary Signs in Various Diseases Table 44-13. migraine" 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. Signs speaking against the diagnosis of "ophthalmoplegic Onset in middle age No history of 12revious 12eriodic headache attacks No nausea, vomiting, and so forth, with 12aral,Y!ic attacks Single or very few e12isodes with long intervals, or 12rolonged headache Permanent 12alsy after a single or very few attacks In attacks I onset of sudden 12ain rather than crescendo Simultaneous onset of 12ain and 12alS:)1 Pain shorter than hours or longer than a few days Pain non-throbbing, even I and severe over days Pain occurring in many short bursts Palsy not im12roving after one or two weeks !at least in early attacl<s) Pueil seared during earalytic eeisodes Painful attacks not triggered b;)'.vasodilator drugs or helped by ergotamine Fever, cerebrospinal fluid changes, or other signs of general aisease triction of the main artery, reduction of edema, increased intravascular pressure, and improved circulation in the small vessels that are released from external pressure may all have been effective together. 8 (3) Clinical Significance-"Ophthalmoplegic migraine" is a rare condition that often has been confused with other syndromes (see Table 44-9). When artcriogram first became widely used, so many patients with intermittent hemicrania and eye muscle palsies were found to have aneurysms or other vascular malformation that some authors began to question whether there actually was such a thing as "ophthalmoplegic migraine." The previously cited discussion of Kennedy against Merritt and others illustrates this. However, there appears to be no question that migraine-like conditions of periodic hemicrania can be associated with paralytic episodes. Depending on the vascular segment affected and on its relation to neighboring nerves the oculosympathetic fibers ("cluster headache"), the oculomotor nerves ("ophthalmoplegic migraine"), or other nerve paths may be involved. Aneurysms, tumors, diabetes, sphenoid mucoceles or other infections, and the syndrome of "painful ophthalmoplegia" (Tolosa-Hunt syndrome) all can cause intermittent head pain and oculomotor deficit; but they all differ from the picture of migraine-like periodic hemicrania in a number of respects (Table 44-8). The signs listed in Table 44-13 speak against the diagnosis of "ophthalmoplegic migraine." 8. Vijayan ( 1980) described a 37-year-old woman who was seen during her third attack of headache and ophthalmoplegia in which the pupil was spared. Based chiefly on this case the author suggested that the third nerve deficit in ophthalmoplegic migraine was likely due not to pressure but to ischemia of the nerve trunk, as in diabetes. "Swelling, exudation , and chemical inflammation" of the (carotid or basal) artery involved in the headache attack was thought to bring about short-lasting occlusion of small nutrient arterial twigs to the third nerve trunk. For Vijayan's case this mechanism indeed appears likely. However, the case differed from the typical description of ophthalmoplegic migraine in several respects: there was no family or personal migraine history, and no painful episodes before or between the three ophthalmoplegic attacks which occurred at intervals of 12 and 11 years; further, the pain came on as a dull bifrontal ache four days before it Statistically, of course, the chance is small that a given patient with sudden, non-traumatic onset of unilateral head pain and ophthalmoplegia has "ophthalmoplegic migraine" rather than an aneurysm. But when there have been regular attacks of migranious headache from childhood; when the pain is preceded by malaise and restlessness, is accompanied by nausea and vomiting, and is triggered by alcohol and vasodilator drugs and aborted by ergotamine; when, after years of these frequent bouts of "sick headache," the patient develops slight ptosis, mydriasis, and diplopia after an especially violent attack; when the motor deficit sets in just as the pain and nausea abate and then resolves quickly; when the paresis gradually becomes more marked and longerlasting with repeated episodes, until some degree of motor loss persists throughout the pain-free intervals; when all this occurs on a background of perfect health; and finally, when the headache bouts become less intense and less frequent as the patient grows olderthen it is a fair assumption that the condition is "ophthalmoplegic migraine" and not an aneurysm. 9 Of all the muscles innervated by the third nerve the pupillary sphincter is affected most consistently and most severely. This is important from a practical viewpoint in that the pupil may serve as an early indicator of oculomotor impairment. In addition, it supports the view that the third nerve defect is caused by pressure rather than by infarction of its nutrient vessels. concentrated in and around the eye. It then continued as a steady, nonthrobbing pain and did not abate before the paresis started. Instead, it accompanied the third nerve palsy for another three days, and nausea and vomiting also developed after the paralysis had begun, about 5 days after the onset of pain. 9. The hazard of complications after arteriography in patients with migraine has been mentioned repeatedly. Hemiparesis or hemiplegia, with or without aphasia and confusion, convulsions, coma, and even death have occurred (Rowbotham and associates, 1953; Alpers and Yaskin, 1951; Wolff, 1963; Patterson and associates, 1964; Walsh and Hoyt, 1969). Fortunately the availability of brain scans and venous digital subtraction angiography has greatly reduced the need for arteriograms in recent times. 44. Vascular Conditions / 1537 E. Cerebrovascular Accidents The cerebrovascular diseases clearly rank first in frequency and urgency among all neurologic disorders. At least 50 percent of neurologic problems in a general hospital are of this type. (Adams and Victor, 1977) 1. Summary By far the most common cerebrovascular diseases are strokes. Usually they are due to infarction of brain tissue after thrombosis or embolism to a blood vessel, especially when there is insufficient collateral circulation to the affected area (Table 44-3). Because of the catastrophic nature of these conditions it is not surprising that generally not much attention is given to the pupillary pathology of patients with acute strokes. Many times, however, the pupils are involved (Table 44-1). A few syndromes stand out either because of their common occurrence or because of interesting combinations of pupillary and other signs. (1) Hemorrhagic or occlusive defects of vessels that irrigate the lateral medulla and pons-the vertebrobasilar arteries and their branches-intercept the descending sympathetic fibers. A "central" or "first neuron" Homer's syndrome therefore is usually found on the side of the lesion. (2)Pontine lesions placed closer to midline may cause "pontine miosis," that is, bilaterally tightly constricted pupils which respond to light only over a narrow range. (3) More cephalad damage to the rostral midbrain and the mesencephalic-diencephalic border zone can injure both sympathetic and parasympathetic pupillary pathways, separately or combined. The sympathetic fibers are caught as they descend from the hypothalamus and subthalamus in the lateral midbrain tegmentum. The efferent parasympathetic fibers may be destroyed as part of nuclear or fascicular midbrain lesions (Weber's and Benedict's syndromes). And spastic miotic or Argyll Robertson-like dissociated pupils result from interruption of both the light reflex path from the pretectum to the third nerve nucleus and the inhibitory fibers that approach this nucleus from more rostral areas. Additional ocular defects associated with these pupil signs often are vertical gaze palsies, convergence difficulties, nystagmus (including, besides horizontal or vertical, rotatory and retractory components), upper lid retraction, and cerebral visual loss. The vessels involved in these lesions are the basilar artery, the posterior cerebral arteries, and the penetrating branches of these arteries to the brainstem. (4) More rostral yet, thrombosis of the thalamic or choroidal branches of the posterior cerebral artery, or of the carotid artery (infarction of the territory of the anterior or posterior choroidal, or penetrating branches of the middle cerebral artery) may contribute to pupillary pathology. The hypothalamic sympathetic centers or subthalamic-lateral mesencephalic part of the descending sympathetic fiber tract may be damaged. Such lesions bring about contralateral sensori-motor defects and ipsilateral oculo-sympathetic loss, together with vasomotor and sudomotor deficit, that extend to the face and body on the side of the lesion. (5) Internal carotid stenosis or thrombosis can also cause ipsilateral postganglionic sympathetic impairment of the eye, without facial vasomotor or sudomotor loss except for a small patch of skin above the brow. This type of deficit probably is caused by occlusion of small nutrient twigs from the carotid artery to the postganglionic sympathetic fibers which accompany the artery in the pericarotid plexus (see Figure 20 in Chapter 25). Moreover, occlusion of nutrient vessels to the pregangli- Figure 44-10. Cross-section through the human medulla at the level of emergence of the twelfth nerve. Note that the sympathetic efferent fibers run in close proximity to the descending fifth nerve nucleus and tract. The darkly shaded area at the right shows the location of lesions causing lateral medullary syndromes, usually vascular in origin. 1538 / V. Pupillary Pathology: Pupillary Signs in Various Diseases Table 44-_14. "Central H?rner's syndrome" due to hemorrhagic or occlusive medullary lesions: Literature reviewed VEAR 1808 1810 1874 1881} 1883 1881 1893 1895 1896 1901 1902 1903 1903 1906 1907 1907 1908 1909 1910 1911 1913 1915 1916 1920 1922 1923 1924 1924 1924 ATTTHOR Vieusseux Marcet Baerwinkel Senator StrUm~ll Heyse #2 Wallenberg van Oordt Wallenberg Babinski & Nageotte 1H Combes #1 Cestan & Chenais Millier Bumke HM Thomas Spiller Wilson Harris Uhthoff Robinson Marie & Foix Marie & Chatelin §Qiller Wallenberg Marinesco & Dras:2nesco Philibert & Rose Ramsbottom & Sto_pford Richter YEAR 1925 1927 1927 1928 1929 1930 1930 1931 1931 1934 1935 1936 1936 1936 1937 1938 1942 1943 1943 1943 1946 1950 1950 1950 1953 1955 1957 1957 1958 AUTHOR Foix & al. Ahrend Dore Roe:er & al. RH Thomeson Merritt & Finland Riley Best Harris & Hauser Peserico Lhermitte & al. Foerster Goodhart & Davison Resnik Harris & Hauser Lichtenstein Stead &al. Adams Freeman & al. Olivier & de Morsier Kubik & Adams Jaffe Uichelle & al. Luhan & Pollock Okinaka & al. KrayenbUhl Bonnet Deronesne Baker YEAR 1958 1958 1958 1958 1959 1961 1961 1961 1961 1961 1962 1962 1962 1962 1962 1964 1965 1967 1969 1969 1969 1971 1972 1973 1973 1974 1974 TI8"r AUTHOR Barbizet Bonnet Fisher & al. Giles & Henderson Minor &al. Baker Bergougnan &al #2 Currier Rial. Fisher & al Serra trice Baasch & al. Delahousse Haymaker & Kuhlenbeck Moberg & al. Smith & Eskridge Delahousse Loeb & Meyer Labaue:e & al. Currier (cit. Jf6rnsten) Haymaker Walsh & Hoyt case# 11~6\i HS Thomeson & Menscher Caelan Rosselet Varela de Seijas & al. Caelan Jf6rnsten Spencer & Czarnecki onic sympathetic chain or the superior cervical ganglion may be responsible for the common occurrence of Homer's syndrome of unknown etiology that appears abruptly and later fades again just as mysteriously (Tuckett, 1905; Sears and co-workers, 1974). (6) When the vascular occlusion results in marked reduction of ocular blood flow the iris is damaged. It becomes edematous and shows other inflammatory signs. Chronic ischemia brings on iris discoloration, patchy stromal atrophy, and neovascularization (rubeosis iridis). The pupil in such eyes is fairly large and poorly reactive or unreactive to physiologic stimuli as well as to all drugs. This damage, as well as retinal changes of a similar nature, can be combined with cortical visual defects. 2. Vascular Lesions of the Caudal Brainstem (a) "Central Homer's Syndrome" The many eponyms coined to describe the effects of vascular brainstem lesions have been listed in Chapter 25. The following is a short summary. Lateral medullary and pontine lesions that intercept the descending oculosympathetic pathway are more often due to vascular disease than to any other pathology. A "central Homer's syndrome" may be part of infarction of the entire half of the brainstem (vertebral artery or vertebro-basilar occlusion), or a more discrete !esio~, as in the lateral medullary syndrome (posterior mfenor cerebellar artery, or superior, middle, or inferior medullary artery). The sympathetic fibers run in close proximity to the descending fifth nerve nucleus and tract (see darkly shaded area in Figure 44-10). Because of this location, the "central Horner's syndrome" often is combined with pain, numbness, and sensory loss over the ipsilateral side of the face. Additonal signs include lateropulsion of the eyes (Hoyt and Kommerell, 1974), ataxia with falling toward the side of the lesion, caused by damage to the inferior cerebral peduncle, cerebellar hemisphere, olivocerebellar, and possibly spinocerebellar tract; vertigo, nausea, and nystagmus due to impairment of the vestibular nucleus; and dysphagia, hoarseness, and paralysis of the palate and vocal cords due to destruction of the emerging ninth and tenth nerve fibers. Involvement of the cuneate and gracile nuclei brings about ipsilateral numbness of the arm, trunk, or leg; and that of the spinothalamic tract, impaired pain and temperature sensations over the opposite side of the body. This syndrome, described so well by Vieusseux two hundred years ago, has become known as "Wallenberg's syndrome," and a great many cases have been described (see Table 44-14 and Figure 44-11 and Figures 25-13 and 25-14). Further rostrally, occlusion of the anterior inferior cerebellar artery (inferior pontine level) will cause additional ipsilateral deafness and tinnitus (involvement of the auditory nerve or the cochlear nucleus), facial paralysis (seventh nerve or nucleus), and loss of conjugate gaze toward the side of the lesion. Infarction of the territory of a short circumferential branch of the basilar artery will add paralysis of the muscles of mastication (motor fifth nerve; see shaded area in Figure 44-12). And occlusion of the superior cerebellar artery will bring about paresis of ipsilateral conjugate gaze, skew deviation, and loss of optokinetic nystagmus. In all these conditions the pupil on the side of the lesion is smaller than that on the opposite side, due to interruption of the descending sympathetic pathways (S in Table 44-15). It has often been said that in patients with "first neuron" central sympathetic defects the affected pupil continues to dilate to instilled cocaine, in contrast to the loss of cocaine response after peripheral sympathetic lesions. We have, however, observed several patients with "Wallenberg's syndrome" and with poor responses to cocaine on the side of the lesion (see Figure 44-11). The discrepant reports probably are based on the fact that central lesions are more often partial than are peripheral lesions: as has been described in Chapter 6 above, a small group of the descending sympathetic fibers decussate at the level of the cervical cord. Contralateral fibers are thus spared in cases with unilateral brainstem lesions, so that some dilation to instilled cocaine would be expected on the affected side, but not as much as on the normal side. 44. Vascular Conditions I 1539 (b) Pontine Miosis "More me ially ituated pontine lesions can bring about a characteri tic pupillary ign referred to under the name of "pontine mio i ." It has been known for a very long time (PM in Table 44-15). The pupils are tightly constricted, and they appear fixed: in many report the light reflexe were aid to be abolished. But often the reflexes are only exceedingly small and luggish (and are therfore overlooked) because of the tiny resting diameter of the pupils. Unlike ympathetic deficit in lateral brain tern lesions, most pontine le ions cau e bilateral mio is, u ually equal in the two eye , even when the lesion is confined to one side. It is therefore impossible to blame the mio is on loss of sympathetic outflow to the eyes. The mechani m of pontine miosis has been discussed in detail in Chapter 9. In the present connection it suffices to know that the miosis is due to disinhibition of the pupillary con trictor nuclei in the midbrain, se~ondary to a defect in the reticular system of the lower bramstem. Just as in experimental animals, the lesion need not be large: damage to discrete sites in the pons can cause dysfunction of the extensive reticular fiber system whose integrity is essential for the maintenance of consciousness and of the "awake" pupillary size and reactions. Figure 44-11. Central Homer's syndrome due to lateral medullary infarction ("Wallenberg's syndrome"). The patient, a 63year-old man, had suffered a classic lateral mcdullary stroke 3 years before examination. He had recovered well. with only slight numbness of his right face and reduction of pain and temperature sense on the left side of his body and extremities. He had a rightsided Homer's syndrome: there was mild "upside-down" ptosis, sudomotor deficit of his face and body, relative miosis, and reduced pupillary dilation to psychosensory stimuli (A). His right pupil dilated less than 0.5 mm to instilled cocaine (three drops 2%), while the left pupil dilated more extensively (B, recorded 45 minutes after instillation of the drug into the conjunctiva! sac of both eyes). Figure 44-12. Cross-section of the human brainstem at the pontine level. Occlusion of the anterior cerebellar artery produces damage in the shaded area, including the ip ilateral descending sympathetic path. 5th NEHVE BASILAR AHTERY-0 1540 / V. Pupillary Pathology: Pupillary Signs in Various Diseases Table 44-15. "Central Homer's syndrome" and "pontine miosis" due to hemorrhagic or occlusive pontine lesions: Literature considered YEAR AUTHOR YEAR AUTHOR YEAR AUTHOR 1851 1872 1872 1874 1876 1877 1881 1881 1883 1886 1889 1892 1893 1893 1894 1899 1905 1911 1914 1922 1922 1927 1927 1927 1931 1932 1935 1936 1936 1957 1957 Biesadecld ( S) Hutchinson (PM) Jackson (PM) Eichhorst (PM) Nothn~el ( S) Seeligmiiller ( S) Leeser (PM) Schiltz (PM) Naether (PM) White {PM} Marimd {PM} Holmberg (S) Heyse ( S) Starr (S) Shimamura * Marimd (PM) §Eiller ( S} Uhthoff (S) Rindfleisch / PM Hassin /PM\ Levser /PM\ Ahrend #2 ( S) 1936 1941 1942 1943 1943 1946 1950 1950 1951 1956 Pilotti ( S) Menninger (PM} Ka:elan ( PM) Parsons (PM) Lhermitte ( S) Foerster ( S) Goodhart & Davison ( S) R.esnik ( S) Freeman & Jaffe (PM) Rowbotham (PM) Freeman &al (PM, S) Adams (S) Kubik & Adams (PM) Lcchelle & al ( S) Luhan & Pollock ( S) Biemond /PM) Cogan (PM) P. Bonnet ( S) Symonds & Mackenzie #4 (PM) 1958 Bonnet (S) 1958 Fisher & al ( S) 1958 Sorsbv IS\ 1959 Guillaumat (PM) 1959 Merone (S) 1961 Bergouggan & al ( S) 1961 Serratrice ( S) 1962 Van Buskirk (PM\ ~ Bodechtel (PM) 1965 Loeb & Me:i-:er ( S) 1967 Fisher (PM) Haymaker ( S) 1969 1969 Walsh & Hovt ( S) Caplan (PM. S) 1974 1975 Gilroy & Meyer (S) Adams & Victor ( S) 1977 ( S) indicates sympathetic deficit and (PM) bilaterally constricted pupils with poor, sluggish light reflexes r•pontine miosis'?; * description of pontine blood supply in man. ADDITIONAL REPORTS: 1971, Thompson & Mensher (S); 1974, Smith (PM); 1983, Spencer & Czarnecki ( S ). 3. Vascular Lesions Affecting the Rostral Brainstem (a) The Diencephalic-Mesencephalic Border Zone Some complex and interesting pupillary syndromes can result from vascular lesions in the rostral midbrain and the diencephalic-mesencephalic border zone. Occasional cases with small infarcts in this area are especially instructive. -The pupil on the side of the lesion may be enlarged and react poorly or not at all to light or to light and to near vision. -A "central Homer's syndrome" may develop, with vasomotor and sudomotor deficit covering the ipsilateral face and lower areas of the body. Figure 44-13 shows the approximate location of the descending sympathetic fiber tract at this level of the brainstem. - The pupil can be small and sluggish or fixed; or an Argyll Robertson type of light-near dissociation may be found (Figure 44-14). -In some patients several of these pupillary defects are combined (Table 44-16), and both pupils may, of course, be pathologic. These pupillary defects are often associated with a distinctive group of extraocular disturbances: loss of up-gaze (Parinaud), or of down-gaze (Andre-Thomas), or of all vertical eye movements; paralysis of the third or fourth nerve; skew deviation, ptosis or-more oftenretraction of the upper lids (Collier's sign); diplopia and various kinds of nystagmus: vertical, horizontal, rotatory, or retractory. Depending upon individually variable details in the course of vessels and the size and location of the infarct within the small and crowded area of the brainstem, there are additional neurologic defects such as contralateral motor and sensory loss, tremor, and ataxia (Claude's, Weber's, or Benedict's syndromes), or impairment of other cranial nerves. Cerebral hemianopia or total blindness with reactive pupils, and often with aphasia, confusion, and other cerebral signs may occur, due to interference with blood flow in the rostral basilar and the posterior cerebral arteries. In the past small, sluggish pupils in such patients, and especially "dissociated" pupils resembling the Argyll Robertson syndrome in all details, were viewed with suspicion. Could these patients not have had Argyll Robertson pupils all along, and could their strokes be brought on by syphilitic cerebrovascular disease? However, this could be ruled out with confidence in a great many cases. And further, consideration of the course of nutrient vessels in the upper brainstem explains the pupillary and associated defects. As seen in Figure 44-13, small vessels from the posterior cerebral artery and the posterior portion of the circle of Willis supply the rostral midbrain and caudal diencephalon. (1) Shortly after the bifurcation of the basilar artery the posterior cerebral arteries give off fine penetrating branches to the paramedian part of the midbrain. Occlusion of these vessels can damage the oculomotor nucleus as well as the efferent (fascicular) third nerve fibers. 44. Vascular Conditions / 1541 ..·:=:-:::-::;. .-··· ..=fJ}B%\) .... , _ -CIRCUMFERENTIAL BRANCHES pt~~dt{bJ ••• Figure 44-13. Cross-section through the human midbrain. The shaded area indicates the approximate location of the descending sympathetic fiber tract from the diencephalon. This area often is damaged by vascular lesions. BRANCHES !",•, ••••••••• ••..•. ,:, •••••••• ·--·\\.:,:i ..:.•:.•.·.·.· ..·,·,.. -- ..... ,,i-'\t,:i:;,: i' .-::;:f· :;:,;::ff/Y' /. ,,, '::' / POSTERIOR CEREBRAL- I BASILAR A. POSTERIOR COMMUNICATING 5 4 -~! '--~ 3 - -\- UNCULAR PENETRATING BRANCHES ARTERIES A i_l 11 B ~:~' ~ --, I ,,.__........ ' - ----\-, ~----- -1-,1_ ,.,1 I .r.f-' 2 ....----- - ----·-, II.I.I 0 I"-' 5 4-~ 3 2 c 2 1\1---l.St\J---J- 1 + 5 _! ___ ..,,,,.....____.,. ,_-......_.,._ • + • • ••••• ♦♦♦♦♦ D-·1-\ -----I 1 t E E 6 5 4 3 2 l.r. ~ E-1-=----- 1 FY.I - .....__,..- --i_J- ~--- ---=---=----------------:-----1 - ·---- NV. Figure 44-14. Monocular elevation paresis and dissociated pupillary light reflex due to a small midbrain stroke. The patient, a 49-year-old man, had sudden onset of diplopia and retro-orbital pain while playing billiards. The pain subsided in a few days but the diplopia persisted. Three months later he complained of diplopia when looking up. This diplopia was due to a reduced range of upward movement of the left eye (from 25 to 30°, compared with the normal 40°). This defect in elevation was the same from the primary and from all other horizontal positions of gaze. There was no ptosis, exophthalmos, or lid retraction. The cover test and Maddox rod test revealed no vertical phoria in the primary position, and there was no secondary deviation on upward gaze. Convergence was normal, but Bell's phenomenon was reduced to the extent of the elevation weaknes . The pupils appeared normal when tested with a flashlight, but the pupillogram ----- .!., ----- I.I.I __ HHH I 4~~ 3 2 .,,,- ------------- ~,c.,",.::,""c.,'-'~.,~- ,__Y sl - -----~SC2--\.J_ ........ \.. I ............ 1.1~1 -------- -- ,----------- - ---- - FV. showed reduced light reflexes on the right side. Further, while the right pupil (solid lines) limped behind the left one (broken lines) during the contractions to light (A to D) it constricted as extensively as the left pupil during near vision efforts (E). Tests of the cerebrospinal fluid and blood (including sedimentation rate, tests for syphilis, thyroid studies, and fasting blood sugar and glucose tolerance tests) were all normal. X-rays of the skull. optic foramina, and chest revealed nothing abnormal. The Tensilon and prostigmine tests as well as the forced duction test were negative. The EEG also was normal, and vision was unimpaired. The EKG showed evidence of an old myocardial infarction. Six months later there was no change in the patient's clinical status. Since the diplopia was present only on looking up, it was tolerated well. (Case described by R.S. Jampel and P. Fells, Arch. Ophthal., Chicago, 80 [ J 968]:45) 1542 V. Pupillary Pathology: Pupillary Signs in Various Diseases Table 44-16. Pupillary signs due to vascular lesions affecting the diencephalic-mesencephalic YEAR AUTHOR FINDINGS 1 63 Weber ~ 52 had stroke 1866 1 70 Ogle Oyon area -+R hemiparesis &sensory loss, incl. face & tongue; L 3rd N paresis with large poorly_reactive pupil; R body warmer than L; clot in inferior medial cerebral peduncle on the left ' £Cclusion of middle cerebral artery causing 3rd nerve deficit cl"' 72 had stroke -.L hemiplegia, incl. face; R 3rd N palsy with pupil R< L, reactions relatively _spared i_ R ?9Bt. _cerebral artery occlusion with softening in cerebral peduncle & thalamus 1872 Peltzer ~ 60 with 0fectious endocarditis had stroke -. sudden blindness, fairly small, fixed pupils; embolism of b_as1lar & both post. cerebral arteries: lesions in both thalami, occipital lobes & colliculi 1880 Kahler &Pick: thrombosis of svlvian Iossa artery with R ptosis &esotropia; lesion in substantia nigra &R red nucleus 18 7 Leu be ~ . 50 w~th L ?~mi paresis, R slight ptosis, both pupils miotic & fixed: scattered small hemorrhagic •-=--.----,-•=m1dbr_arn foc_1 in midline near 3rd N nucleus; also in R peduncle & substantia nigra 1889 Oulmont cl"' 67 in semicoma -.variable consciousness: completely blind with large, almost fixed pupils; L •-~-----• _arm paralyzed: atheromas in basal artery, complete loss of occipital lobes & surrounding area ~ Jakob ~ 3~, sudd~n hemiplegia & sensory loss, incl. face; L total 3rd N palsy; R poor vertical EOM, ptosis, horizontal & rotatory nystagmus; pupil reactive; died 19 years later: aneurysm in collicular area & large brain stem hemorrhage, incl. L thalamus, pulvina, int. capsule, ant. colliculus & -::-::,-:,oc--•·-=c----,-,---•-midbrain te<nnentum to rostral oons • L total & R partial 3rd N nucleus 1 96 Rosso limo ~ 48, history of alcohol & "migraine" since age 25: 3 small strokes in 4 months _.died; had R hemianopsia, paresis R arm & 7th N, aphasia; R 6th & L 3rd Ns paretic; bilateral accommodative loss; pupils R < L, almost fixed OU; hemispheric & brain stem softening due to occlusion of penetrating branches of basilar & posterior cerebral arteries ~•-,.b.;;e~r;:;c:;;u-;,m;:;:;---l~~--;6;-,2,:c~::,1,..th:;:-'~R'_'.::h'=e:'::m:':7ip""la':e:':g='ic::a=-,.:::.,:h=e=m=;ia=-n..::e=-s..ct:'ih-"e:..:s:::i;..a.:::,~R~h::..:o:.:m::..:o:::..::.:ny::::::..m.:::o aphasia, pain R arm 1902 Josserand ~ with sudden blindness, pupils fixed to light _. died soon; atheroma of basilar & of both po st. ____ arteries; bilat. softening of occipital lobes; data on brain stem not yet available 1._______ 1_cerebral Spiller #6 1905 cl' 63, alcoholic, sudden vertigo & blurred vision, ankle clonus R > L, loss of up-gaze, pupils sluggish to light. constricted more extensivelv to near vision _. improved 1909 Guilain & al Q 59, had stroke_. R hemiplegia, incl. face & L EOM palsy; L pupil<. R; L poorly reactive to light with good reactions to near vision (Argyll Robertson) 1911 Holmes & OW 49 with chronic Bright's disease & enlarged heart, had 3 strokes at short intervals --. slight 1912 R motor & profound sensory loss with pain & hemiataxia; partial deafness, poor memory & attention; Bead pupils small &fixed to light; extensive softening in L ventro-lat. thalamus, reaching caudally mesial to inferior pulvinar at level of posterior commissure 19TrMills a11ated pupil & crossed hemichorea, hemiataxia & hemiparesis: thought lesion near nucleus 7 ruber ~ • -~D;:.e:;;j=e=r~rn-e--•-,,~=c.:.::4,.:0~, ..:;2Fy.::.e...::a=-r-=s-=..::e-=a:.:r°'li°"· e=-.::.r:.:s:.:u:::d:;d:;e:.:.n::..::,R:-=h,z.e-'m=:i=-=p=::l=e:.:g.,::ia=-=, =-d,.:y=-s-=a:.:r..:;t=r=ti"-'a..:;&a-=-:d'i'ii:.:p:,,;loc..p:.:ia,;.c. :.=_."-=-:...c,.im=-=-p:.:r=-o-v-e-'d'i-"_.'---:::-"-'v""e-'-r-,t ig-o-'--, ----t & al diplopia, R hemiparesis & L llorner's & Argyll Robertson; lesion assumed peduncular & midbrain tegmentum, pPriaqueductal & reticular formation ~ 53 with stroke had L hemiparesis, incl. 7th N, hemiopic pupil without hemianopsia; puplls Wilbrand ~ were L > R, light reflexes R > L but near vision contractions R = L (dissociated) & Behr 1917 Wilbrand & P. 97 case of cortical blindness with Argyll Robertson after atheroma of basal & both posterior Saenger cerebral arteries with softenine: of occipital lobes --=-1-=9""2-=1-•-~Sc:--,h-u-s""'t"'°e_r ___ •-==~ 62, paralysis of upward gaze & bilateral Argyll Robertson pupils: small softening in deep ____ , ________ , __layers of midbrain tegmentum, skirting the aqueduct on the R side Lenz & 0-'r 63, sudden loss of all L and part of R visual field -. R field regained; both pupils small & 1925 Schwab fixed to light, prompt to near vision for several days; also pseudo-bulbar palsy & Parkinson-like rigidity, poor equilibrium; assumed occlusion of basilar artery ~ 53 had stroke _. L hemiparesis & aphasia; R pupil> L; R light reflex reduced but reactions 1926 Behr to near vision were equal ( dissociated on R) ~ 49, sudden R hemiplegia, hemianesthesia, transient aph_asia; extre~e lid r~traction & ~ss of Collier #i ~ vertical gaze OU; loss of convergence & of R-gaze; both pupils small, fixed to hght : had circumscribed capsulo-thalamic hemorrhage L, reaching down to posterior commissure in-- ~ 69, hemiplegia, R ptosis, external ophthalmoplegia & small pupil, fixed to light; L lid retraction -+improved: R ptosis changed to lid retraction, pupil redilated & reacted to light; assumed ____ commissure 1_______ 1_lesion in area of posterior (fl 67 had stroke _. L hemiparesis & confusion ---. improved but had bilateral lid retraction, Thomas & 1932 down-gaze palsy & convergence paresis; pupils reacted feebly to light & normally to near vision; Schaeffer L central 7th N oalsv. labvrinthine areflexia; assumed lesion in rostral midbrain to thalamus Alajouanine ~ 46 had stroke -. R hemiplegia & hemianesthesia, incl. face; R deaf & corneal anesthesia; 1934 & al L Horner' s, bilat. loss of up-gaze & of light reflex with near-vision contraction intact; recovered except for R anesthesia & paresthesia; assumed thalamic hemorrhage with pressure to int. capsule, posterior commissure, colliculi & subcollicular area Chavany & IO"" 57, sudden staggering, nausea, somnolence, weakness ---. improved; had ptosis, OS deviated 1934 Lemoine out, loss of up-gaze; pupils R < L medium size, L fixed & R poorly reactive to light, both responding well to near vision; -4-hearing; assumed hemorrhage in rostral midbrain around aqueduct to subcollicular area Orzechowski ~ 30, sudden hemorrhage _.. L decerebrate rigidity -+- L leg paretic; bilateral loss of up-gaze & 1934 & Jarzymsk· of convergence; light reflex abolished, lid retraction OU ---. recovered except for lid retraction; assumed hemorrhage near red nucleus, breaking into aqueduct or 3rd ventricle = extraocular movements; DTR's = deep tendon reflexes; (n.r.) = not read at ,..= decreased;t = loss of upward gaze; R = right; L = left; AR= Argyll Robertson EOM time of writing ;-+progression pupils. to; 44. Vascular Conditions Table 44-16 YEAR 1935 1935 1938 1940 ___ 1941 1941 1941 1942 1942 1946 1947 1949 1950 1951 1955 1956 1957 1959 1960 1963 1966 1967 1968 1974 1974 1975 1976 1977 1976 1976 / 1543 (continued) AUTHOR Guillain & Alaiouanine Lhermitte & al Sala FINDINGS {cit. by P.Bonnet): peduncular lesion with Parinaud's syndrome, Horner's syndrome and Argyll RoQ..Qbe~r:tts~o~n!:!..Jp~uyp~iJl ________ ~~-=---=--,------,,-----,.-,--,~--;,::-=-;=---=;;-,.::--.c::;;-;;::-;:;-;:;;~ai:;-'i;r.;;;--;;-;;;;;;:-::--1 O"' 49, sudden L Horner's pupil &Argyll Robertson syndrome; facial pain &reduced 5th N sensa tion, loss of sense for hot & cold L dorsum of foot; DTR' s R> L . . . . ~ 35, hypertensive, late in pregnancy came down \~th ~udde_n L hem_iparesi~ &•acuity, lowe:J-' 7th N palsy, paralysis of up--gaze, bilat. lid retract10n, impaired pupil react10ns _.. recover L hemiplegia & hemianestbesia, anosognosia & delusions of body scheme, with up gaze palsy, Olsen & weak convergence, divergence & lateral gaze, impaired light reflex; autopsy showed hemorrhage Millitzer , ________ 1_in R thalamus & mesencephalon Faurectr 68 had stroke -+ staggered & fell to L; DTR' s R >Lin legs with plantar exten_s1on, trembling Beaulieu & in arms, ataxia; Reye in divergent squint, loss of up-gaze OU; pupils large &fl.Xe?, R~L ___. improved, with some near-response but light reflexes & up-gaze still absent { AR dissocrnt10n); Isorni assumed lesion in area of colliculi and posterior commissure . Lhermitte peduncular hemorrhage with loss of up-gaze and of light reflex UO; Horner's syndrome on side of & al lesion (right side\ Freeman & embolism of sup. cerebellar artery in O"' 44: confusion & tremor in L arm & hand, bilatera~ • Jaffe hearing, cerebellar signs; analgesia for pain & temperature in R body, incl. face; DTR' s mcreased, pupils both small & sluggish, plus Horner's L with facial anhidrosis Parinaud's syndrome, conjugate deviation, bilateral iridoplegia & Horner's syndrome due to Lhermilte peduncular hemorrhage #2 cases with hemianopsia and Argyll Robertson syndrome (n.r.) Ramirez 18 cases with occlusion of basilar artery (11 thrombotic, 7 embolic) & case reports; #2 had homoKubik & nymous hemianopsia and small pupils, barely reactive to light; #3 had hemiplegia, small, unequal Adams pupils, fixed to light; 1 patient who survived had loss of up-gaze & small pupils, fixed to light; pupils were seldom normal: 6 x fixed, or dilated as part o: 3rd nerve palsy . . . . . O"' 68 had L hemiplegia, cerebellar signs -cerebral blmdness; later periodic diploprn, pupils Lutt sluggish to light -+ irregular AR pupils and left hemianopia; thrombosis of cerebral, cerebellar & brain stem arteries; large lesions in both occipital lobes, small one in mid brain, just rostral to the sup. colliculi, 'l.nd in pons near midline, extending into the mesencephalon O"' 49 with assumed stroke & meningeal hemorrhage had transient R > L Are:vll Robertson pupils Roger &al l1' 50, vertigo & syncope, difficulty speaking & swallowing __... R hemisensory loss, L hypoacousy & Lechelle palsy of palate &vocal cords-deep torpor, palsy L 3rd, 6th, 7th nerves, cerebellar ataxia; &al L Horner s & partial 3rd N palsy; had brain stem lesion, thought to be vascular Q 48, sudden hemiplegia, limited up-gaze, R lid retraction; pupils R> L, R very slow light reflex Sciorta & &limited convergence reaction; vertical gaze & doll's head movements abolished Burruano artery R __...R 3rd N palsy in 60-year-old diabetic patient Krayen bilhl Occlusion of vertebral O"' 21, congenital Parinaud's syndrome L: vertical gaze &convergence abolished but int. rectus Belz & al worked in lateral gaze; had L Horner' s vertigo, diplopia discussion of rostral brain stem lesions {no cases) due to vascular or other causes; both Horner' s P.Bonnet syndrome and Argyll Robertson.pupils occur, as well as hemianopsia, Weber's, Benedict's, Parinaud's and thalamic sindromes and lid retraction 183 cases with occlusive vertebro-basilar disease: 26 bilateral, 21 unilateral, 15 transient; found Minor & homonymous hemianopsia, 73 blurred vision, 50 diplopia, 10 conjugate gaze palsy, 18 nystagmus, Kearns 15 internuclear oohthalmoolee:ia, 8 ptosis; pupils seldom mentioned: 1 had Horner' s syndrome Ajuriaguerr2 cerebral blindness due to thrombosis of basilar-vertebral system: usually sudden onset, or in .:1 & Hecaen stages; thalamic syndrome and/or brain stem signs may be added Bodechtel basilar artery occlusion with pyramidal signs, swallowing & speech defects: sudden onset with vertigo vomiting. confusion ---> coma; involvement of 3rd N nuclei and small nu oils fixed to lie:ht Halcher & 10" 56 with small infarcts of R periaqueductal grey near post. commissure -bilat. loss 01 vertical Klintworth e:aze: convergence & retraction nvstae:mus lid retraction, unequal, sluggish pupils, hemianopsia patients with (hypertensive) thalamic hemorrhages have crossed hemiparesis, impaired vertical Fisher eye movements and small, fixed pupils 7 patients with acquired monocular elevation palsy: #1 had Argyll Robertson-type dissociated Jampel & pupils, #8 fixed pupils: probably due to small strokes in rostral midbrain area Fells Q 78 with cardiovascular disease had sudden L hemiparesis, incl.face, facial hypesthesia, disGrowdon orientation, dysartria, somnolence; full ptosis OU, R ophthalmoplegia; pupils small, reacted to &al light --.recovered except for diminished convergence -died 3 years later: found infarct in dorsal midbrain te<rmentum Jenny & associated signs with Parinaud's loss of vertical gaze include diplopia, simple reflex immobility Leuenberger of pupils, corectopia, partial 3rd or 4th N palsy, lid retraction, accommodative palsy or spasm Les sell Cl' 52 with bronchogenic Ca: monocular elevation palsy & pupils first normal _..mid-dilated and dissociated -+ larger and fixed. autopsy showed tumor metastasis in pretectal area indicated by Jampel & Fells, 1968 as probable site for monocular elevation palsy Vogel Parinaud's syndrome with dissociated pupils, or 3rd &4th N palsy: lesions {some hemorrhagic) in subthalamic-unner neduncular region near posterior commissure Walshe hypertensive thalamic hemorrhages (diagnosed by CT scan): sensorrmotor hemiplegia or hemipare&al sis, limitation of vertical g;aze, downward deviatio~ of _eyes & small, fixed or sluggish pupils Kirkham & monocular elevator palsy with Argyll Robertson pupils rn a 47-year-old woman with sarcoidosis; the Kline authors assumed the site suggested by Jampel & Fells and shown by Lessell Selhorst intermittent corectopia in a patient with rostral midbrain infarction 1544 V. Pupillary Pathology: Pupillary Signs in Various Diseases Ta~le 44-17: "Ce?tral Horner's syndrome" due to hemorrhagic or occlusive cerebral !es10~s: Patients with contralateral sensorimotor deficit and ipsilateral sympathetic impairment YEAR AUTHOR YEAR AUTHOR YEAR AUTHOR 1852 1876 1877 1898 1913} 1914 1914 1917 Ver~a (?) Nothnagel Seeligmliller #9&10 Schmidi-Rim:eler 1936 1938 1938 1939 1940 1941 1941 1942 1942 1943 1949 1950 1950 1951 Schuster #5, 16, 19 Garcin Siegert *3 (OG) Garcin & Ki:efer de Morsier #2 Freeman & Jaffe Lhermitte & al Lhermitte Stead& al Adams Garcin &al Miletti *3 {OG) Sugar & al *3 {OG) Johnson & Walker *3 Hyslop (:eossibl,y:) *3 Schneider & Lemmen *3 Walsh & Smith #7, 11 *3 Riser& al *3 Tolosa *4 McGuire & Jaeger *3 Murray {#1 Qrobably) *2 *3 Elander & al *3 Walsh *3 Bonnet O'Doherty & Green *3 1959 1960 Morone Ajur,a.guerra & Ilecaen Duma *3 Garcin (review) Aquaviva & Serratricc *3 Battistini Beall &al DuPont Guerrv *3 Carter *3 Houck& al *3 Labauge *3 (review) Crill Waltz& Ehni Fleming& Petric *3 Walsh& Hoyt *3 Ma:estonc *3 Jernigan & Gardner *3 Gilchrist *3 Plum & Posner Ca2lan Schi.ffter & Schliack *3 Greiner *5 West & al *3 Grimson & Thom2son *3 Maloney & al *3 Keane 1920 1920 1921 1922 1924 1925 1927 1927 1927 1928 1929 1931 1931 1933 1933 1934 1936 Schrottenbach Dei erine & al Wilbrand & Saenger *1 §eiller Stierlin & Mevcnburg *3 Lhermitte &Fumet Segall Behr *l Foix & al *2 Claude (:erobably) *3 Collier Wilbrand & Behr *l PoEEi Lhermitte &Cornil Guillain &al Weill & Nordmann *1 Bertrand &Garcin de Morsier Alaiouanine & al Lhermitte 1952 1952 1952 1953 1954 1955 1956 1957 1957 1958 1958 1960 1960 1961 1961 1962 1963 1964 1964 1965 1966 1966 ~ 1969 1970 1971 1973 1973 1974 1974 1976 1976 1978 1980 1979 *1: "Behr' s Phenomenon", that is, optic tract lesion with ipsilateral miosis, interpreted as contralateral mydriasis. *2: ipsilateral sympathetic deficit, interpreted as contralateral sympathetic stimulation. *3: Carotid Artery Occlusion; Horner' s syndrome could be due to deep cerebral lesion or to postganglionic impairment (see text), *4: Peri-carotid inflammatory process, "painful ophthalmoplegia". *5: Fibro-Muscular Dysplasia of carotid artery. # = case number in publication; ( OG) cited after O'Doherty & Green, 1958. (2) Circumferential branches of the posterior cerebral artery irrigate the lateral and dorsal midbrain, and infarction here can intercept the light reflex fibers running from the pretectum to the Edinger-Westphal nucleus. The supranuclear inhibitory fibers can be caught in the same general area just rostral to the nucleus. (3) Occlusion of twigs of these vessels can further destroy the sympathetic fiber tract that descends from the diencephalon to the lower brainstem and spinal cord in the lateral midbrain tegmentum. In the past we believed such cases to be rare; but once alerted to their existence in patients with brainstem strokes we did not find it difficult to collect a fair number from the literature (Table 44-16) as well as among the clinical material of our laboratory. lt should, of course, be stressed again that these defects, like any other pupil1ary sign, depend upon the location of the lesion, not its nature. The combinations of pupillary and other pathology here described are also found when tumors or trauma affect the same part of the brainstem. But vascular origin is especially common, and small, discrete lesions are more often due to vascular than to other causes. 10 Jampel and Fel1s (1968) proposed a small infarct, rostral to the third nerve nucleus as the lesion responsible for the interesting phenomenon of monocular elevation paralysis with pupillary signs (Figure 44-14). And in a similar case Lessel (1975) confirmed this site at autopsy. Kirkham and Kline (1976) agreed with this location for a patient with sarcoidosis who had monocular elevation palsy and Argyll Robertson pupils. 10. In an especially interesting report, Nashold and Seaber (1972) described sixteen patients in whom they had deliberately produced stereotaxic lesions in this area for the relief of intractable pain. Postoperatively, all the patients had vergence difficulties; thirteen had disturbed upward, and ten disturbed downward gaze, and in fifteen the pupils were miotic and fixed to light. 44. Vascular Conditions (b) The Diencephalon and Cerebral Hemispheres The most rostral region of the brainstem, the thalamichypothalamic area, contains the neurons of origin of the descending sympathetic outflow. It is supplied by overlapping end branches from both the carotid and the vertebra-basilar arterial trees (Figures 44-15 and 44-16). Deep cerebral lesions in this area, like lower brainstem lesions, can give rise to "central Horner's syndrome"that is, ipsilateral oculo-sympathetic deficit plus impairment of vasomotor, sudomotor, and pilomotor functions of the face and body on the same side--often accompanied by sensori-motor loss on the opposite side (Table 44-17). Depending on the size and location of the lesion, there may be hemiparesis or hemiplegia, loss of various sensory modalities, and so forth. Jn addition, the distinctive "thalamic pain syndrome" of Dejerine and Roussy can be brought on by small defects in the thalamicsubthalamic region (see description in Chapter 25). ln some case reports an ipsilateral sympathetic lesion with miosis and reduction of vasomotor or sudomotor functions was mistaken for sympathetic irritation on the opposite side. But sympathetic irritation is exceedingly rare, and is usually episodic. Such central Homer's syndromes can be caused indirectly by carotid stenosis or thrombosis (spontane- / 1545 ous or traumatic; numbered 3 in Table 44-17). Interference with carotid blood flow can precipitate infarction in the area supplied by small penetrating twigs from its middle cerebral branch, or by the thin anterior choroidal artery. Such lesions have been found after carotid arteriography. It is interesting that carotid artery involvement (especially near or above the carotid bifurcation) can also cause postganglionic Homer's syndrome, probably by occlusion or pressure upon the fine nutrient vessels to the pericarotid sympathetic plexus. In contrast to the central ("first neuron") Homer's syndrome, postganglionic ("third neuron") sympathetic damage is not associated with cerebral signs nor by sudomotor or vasomotor deficit except in a small area above the brow. The two types of sympathetic lesion that can follow carotid artery impairment can be distinguished by this difference in vasomotor and sudomotor function, and by the use of pupillary drug tests (cocaine-adrenaline and hydroxyamphetamine, as shown in Figure 20 of Chapter 25). Occlusion (by thrombosis or emboli) of the most rostral portion of the vertebra-basilar system, the po terior cerebral arteries, causes central blindness (see Tables 17-9 to 17-11 and Table 44-18). When such lesions are limited to the calcarine cortex, they produce z Wt?@ 11 ~5 Figure 44-15. Frontal cut through the human brain. The overlapping territories or branches of the posterior cerebral artery, the middle cerebral artery, and the anterior chroidal artery are shown. Figure 44-16. Regions of the brain supplied by the posterior part of the circle of Willis (sagittal view). I, Posterior cerebral artery; 2, superior cerebellar artery; 3, basilar artery and superior cerebellar artery; 4, posterior inferior cerebellar artery; 5, vertebral artery (posterior inferior cerebellar, anterior spinal, and posterior spinal arteries). Note the overlapping of the posterior cerebral with other vascular territories. (From H. Krayenbiihl and M.S. Yasargil, in Handbook of Clinical Neurology, P.J. Vincken and G.W. Bruyn, Eds. [Amsterdam: North Holland Publishing Co., 1972), Vol. II) 44. Vascular Conditions / 1547 Table 44-19. "Barre-Lieou" syndrome versus vertebro-basilar insufficiency: Literature considered YEAR 1926 1928 1933 1938 1946 1946 1946 1946 1947 1947 1949 1949 1949 --1951 1952 1952 1952 1952 1952 1952 1952 1952 1952 1952 1952 1952 1953 1953 1953 1953 --1954 1954 1954 1954 1954 AUTHOR Barre (BL) Lieou (BL) Viallefont (BL) Lichtenstein (BL) Devic & al. QD__ Merlen ( BL) Paufiquc & Chavanne (F) Roux !El BlirtschiRochaix (BL) Beauvieux & al.(F) Chevassus (F) Gayral (BL) Paufique & Etienne (F) Paufigue & al (BL) Arslan (BL) Barre {BL) Euzi~re { BL) Euzi~re & al. ([) Girard (F) Lazhortes (BL) Mayoux & al. (Y) Paufique & Etienne ([) Roger (BL) de ~ze /BL) Skipper & Flint (V) Streiff ([) Bakay & Sweet (V) Calmettes & al.(F) Mas2etiol & al. (BL) Ross & McKusick {V) Georgiad~s ([) Merle (F) Paufigue ([) Pinchon (F) Redslob (F) YEAR 1955 1955 1955 1955 1955 1956 1956 1956 1956 1957 --1958 1958 1958 1959 1959 1960 1960 1960 1960 1960 1960 1960 1961 1961 1961 1961 1962 1962 --1962 1963 1963 AUTHOR Calmettes ([) Julien & Vincendeau (F) Kovacs Millikan & Sieckert (V) Bordenare & Berthet (F) Ford & Clark (V) Georgiad~s ([) Hutchinson & Yates (V) Unterharnscheidt (BL) Tatlow & Bammer (V) Barbizet (V) Camninchi IF) Georgiad~s ([) Lecog (V) Minor & al. Dowling & Smith (V) Lecog (V) Maduro Martin & al. (V) Neuwirth {BL) Sheehan & al. (V) Whisnant & Sayre Bergouig:!1;an & al. Georgiad~s ([) Huber (F) Powers & al. (V) Djindjian & Pansini (V) Smith & Eskridge {V) Williams & Wilson (V) Brain (V) Jain & Grove (V) m YEAR AUTHOR Paillas & al (V) Rebattu & Bonnefoy ( BL) Tallec 1963 Winther (V) 1963 Delahousse (V) 1964 Favarel1964 Benazet Hectges (V) 1964 Jung & 1964 Vierling (V) 1964 Jun~ & al.(V) Khurana & Hunter 1964 Charbonnel (V) 1965 ~ Jung & Vierling (V) Labauge &al. (V) 1965 1965 Philip & Laborie (V) 1965 Schott & al. (V) 1966 Toussaint & Fabeck 1967 Derouesne (V) Gereaud & al. (V) 1967 1967 Hubault & Dreyfus ( BL , V) 1967 Labauge (V) 1967 Labauge & al. (V) 1967 Takizawa & al. (Y) 1968 Jung & al.(V) Labauge {V) 1969 1969 Rosselet (V) 1970 Cam2inchi & al. 1970 Phili:epot & al. (V) 1971 Fasano & al.(Y) 1971 Rose & al (V) 1973 Rosselet (V) 1970 Serre & al. (V) 1963 1963 In the publications marked (BL) the authors aggreed with Barre and Lieous's theory of the effects of cervical spine anomalies; in the publications marked (F), they also said that Fuchs's heterochromic cyclitis was caused by the spinal-sympathetic condition; in those marked (V) the authors realized that the pathologic changes were due to vertebro-basilar insufficiency, sometimes aggravated by the spinal deformity. Barre concluded that these changes had triggered the patient's symptoms, either directly, by painful irritation of the vertebral nerve which was compressed or stretched by the spinal deformities, or by vasoconstriction, secondary to stimulation of sympathetic vertebral nerve fibers. Such stimulation, Barre thought, would cause brainstem ischemia, especially at the level of the medulla and pons. Thus intracranial dysfunction was produced by an extracranial lesion quite far removed from the parts of the brain that were affected. Lieou, in his dissertation (1928), undertaken under Barre's sponsorship, elaborated on the subject; and soon others found the "posterior cervical syndrome of BarreLieou" in patients with defects of the spinal column. Otologists, ophthalmologists, neurologists, surgeons, and practitioners in general medicine described many cases. The cardinal signs were headaches, especially occipital; earaches and loss of hearing; shoulder, neck, and facial pain; listlessness, vertigo, nausea, and tinnitus. There were peculiar sensations in the neck and arms, and painful paresthesia, especially in the fingertips at night. There could be momentary dysarthria, disorientation, and anxiety. Among eye signs there were nystagmus or vague visual difficulties such as fleeting attacks of dim or of veiled vision. Often the eyes were tired and tearing, with occasional light flashes or field defects, retrobulbar pain, and hypesthesia in the territory of the fifth nerve. These signs usually came on or were greatly aggravated when the head was turned far to the side. Barre's clinical observations and his realization that neck pathology can lead to intracranial disturbances were important contributions, even though his explana- 1548 / V. Pupillary Pathology: Pupillary Signs in Various Diseases tion was only partly correct: as will be described presently, cervical spinal deformities impair cerebral blood flow directly by distortion and pressure upon the vertebral arteries rather than indirectly by way of stimulation of sympathetic fibers in the vertebral nerve. Unfortunately Barre's theory opened the door to a flood of speculations about the "trophic sympathetic nerves" said to run in the "posterior sympathetic plexus" of the vertebral artery. Ophthalmologists eager to blame Fuchs's heterochromic cyclitis, progressive facial hemiatrophy, and even Marfan's syndrome for defects of the sympathetic nervous system played an especially sorry role in these discussions (see Table 41-11 and publication marked Fin Table 44-19). (b) Vertebro-basilar Insufficiency and Occlusion of Other Large Vessels Already in the 1940s occaional patients with the "Barre-Lieou syndrome" were found to have decreased retinal artery pressure or a reduced carotid pulse. And more and more it became evident that all signs of the "Barre-Lieou syndrome" closely resembled those of chronic vertebral artery insufficiency, while none of the usual ingredients of Homer's syndrome were discovered: these patients had no sympathetic miosis or ptosis, nor vasomotor, sudomotor, or pilomotor deficit in their arms or head. To the contrary, their pupils often were enlarged, and they reacted only poorly or not at all to light, to near vision, and to drugs. The ocular defects in these patients were the same as those caused by ischemic inflammation of the eye due to vascular occlusions of various kinds: the iris became edematous, and later darkened and discolored, with patches of stromal atrophy, and with iris cysts or neovascularization on the anterior iris surface. There was a rarefied posterior epithelium, visible on transillumination. There were synechiae, corneal precipitates, and edema; aqueous flare, exudates, vitreous floaters, and ciliary body atrophy; ischemic retinal vessels, proliferating retinitis, retinal and vitreous hemorrhages, and occasionally cataract and glaucoma. In addition, there were tortuous conjunctiva) vessels and swollen lids; desquamation and ulceration of the skin in the face, facial depigmentation of hair, and muscle atrophy. During recent decades new techniques such as the laminogram, arteriogram, and electroencephalogram have proven beyond doubt that in patients with the "Barre-Licou syndrome" because of cervical arthrosis, the vertebral arteries are distorted and compressed by deformities of the vertebrae, especially when the head is rotated (Figure 44-17). Persons with otherwise normal vascular trees may tolerate such defects without symptoms because compression of the vertebral artery on one side is compensated for by blood flow from the other, or from healthy carotid arteries via the circle of Willis. 12 In contrast, when blood flow in these compensatory chan- B A ' l r\P 1 •'' ARTERlAL TWIG TO VERTEBRAL "r,•nl~/.!...!.-...,,.;;::--ARTERY ·& I,_., NERVE ROOT t ~·:!·!~~ .,-·: -:.:..\'·l/ .....11,.1& ,. BACK ,f//1'. (•('r'¥/(~ ,..,..,..,.\\l ••,,,,,tdf~ ,· ......... ,i/u \ .,..,u.;•.,,,rt FRONT -~~ ili.t%. )f)tI~, ll ll~VISON. FRONTAL VIEW PROFILE VIEW Figure 44-17. Distortion of the vertebral artery by osteo-arthritic changes of the cervical spine. A shows the smooth, straight course of the vertebral artery in the vertebral canal of a normal specimen. Band C show drawing of a dissection of a patient with cervical osteo-arthritis. The vertebral artery on the right side was severely distorted. The arrows indicate comparable points on the distorted side in frontal view (B) and in profile view (C). (From E.C. Hutchinson and P.O. Yates, Brain, 79 [1956]:319) 44. Vascular Conditions nels is occluded by atheroma, by a congenitally small or absent vertebral artery on the opposite ide, or by other defects, an already precarious cerebral blood supply will be shut down further, and symptoms will result. These facts explain why ceivical arthrosis, o teophytes and cervical disk degeneration-increasingly common in normal populations after the age of 40, and almost universal beyond 60-are associated with signs ofvertebro-basilar insufficiency in some but not in many other cases. Iris damage and other signs of ischemic ocular inflammation develop with vascular defects at other sites as well (Table 44-20): occlusion of the ophthalmic artery or of the ciliary arteries by emboli, arteritis, surgery such as multiple muscle transpositions, or retinal detachment surgery; impairment of blood flow through the external and internal carotid arteries by thrombosis or emboli; or more remote blockage of blood flow, at the origin of the great cephalic arterial trunks from the aortic arch ("aortic arch syndrome" or "pulseless disease"), sometimes with diversion of blood reaching the brain by way of the vertebral artery on one side (by retrograde flow via the opposite vertebral artery) to an arm whose subclavian artery is blocked (the "subclavian steal" syndrome; Figure 44-18). Systemic diseases that bring on marked hypotension also can cause ischemic ocular lesions. This happens, for example, in the Shy-Drager syndrome and in other dysautonomic conditions. The same can occur when the oxygen content of the blood is chronically reduced, as in some cases of carbon monoxide or other gas poisoning, in blood diseases like pernicious anemia, and in patients with chronic respiratory insufficiency due to pulmonary diseases like chronic bronchitis and emphysema. Acute circulatory failure tends to cause ischemic damage to the brain and the retina sooner than to the anterior segment of the eye. Cerebral blindness, sometimes combined with retinal impairment, can result from many causes. In such cases, cerebral blindness leaves the pupils reactive, while retinal damage causes afferent pupillary deficit; and iris damage abolishes the direct and consensual light reflexes as well as all other pupil_12. lt is in_teresting in this connection that Alexander (1881, 1882, 1883) tied both vertebral arteries in the neck of epileptic patients, apparently without serious mishap: most of these patients were young. Figure 44-18. Vascular insufficiency, and "subclavian steal" syndrome. The most common sites for the formation of artheromatous plaques are shown. The arrows indicate blood flow in cases with the "subclavian steal" syndrome: when the proximal portion of the subclavian artery is occluded (on the right in the picture), blood 1s_drawnfrom the opposite vertebral artery by reversed flow on the side of the obstruction. In patients with "pulseless disease" ("aortic arch syndrome"), all the great arteries are occluded at their origin from the aortic arch. (Modified from F.B. Walsh and W.F. Hoyt, Clinical Neuro-Ophthalmology [Baltimore: Williams and Wilkins, 1969, Vol. 2) / 1549 lary reactions to physiologic stimuli and to drugs. Impairment of the third nerve and of the ciliary ganglion also can occur, and in some cases several of these pathologic mechanisms may be combined. Chutkow, Sharbrough, and Riley (1973) observed such a patient. A 64-year-old man became permanently blind after simultaneous bilateral neck dissection for squamous cell carcinoma. Electroretinographic evidence and the subsequent development of optic atrophy indicated that the blindness was due to infarction of the retinal ganglion cells. The pupils measured 8 millimeters on the right and 6 millimeters on the left side when 1550 / V. Pupillary Pathology: Pupillary Signs in Various Diseases Table 44-20. Vascular conditions affecting the pupils directly or indirectly 1. OCCLUSIVE VASCULAR CONDITIONS "Aortic. arch" sy~drome (or pulse less disease); "subclavian steal" syndrome; vertcbro-basilar insufficiency; carotid or other artenal steno~lB or thrombosis; air, gas, fat, or infective emboli; compression of cerebral arteries by brain edema or by high mtracranial pressure; temporal ( giant cell) arteritis or other arterial disease 2. SYSTEMIC CIRCULATORY FAILURE Cardiac arrest; dysautonomic or other disease with marked vascular hypotension; remote hemorrhage by systemic vascular lesions 3. LOW OXYGEN TENSION IN THE BLOOD Blood diseases; respiratory diseas~s with l'hronic respiratory poisoning, smoke inhalation, and sequelae of severe burns, insufficiency; etc. ritrogen oxide anesthesia, carbon monoxide 4. TRAUMA Apnoea at birth; hypoxia, anoxia, asphyxia, strangulation, drowning; trauma to the neck or upper chest; extensive systemic hemorrhage due to trauma, and traumatic shock; surgical procedures such as arteriogram, ventriculogram; air emboli due to surgery (pneumothorax, abortions); loss of blood and severe drop in blood pressure during surgery, such as du ring bilateral neck dissection 5. OCULAR ISCHEMJC INFLAMMATION Occlusive arterial disease or emboli (vertebral, carotid, ophthalmic, or retinal arteries); tearing or compression of retinal arteries; retinal detachment surgery, acute angle-closure glaucoma; extraocular muscle surgery (muscle transpositions); (giant cell) temporal or carotid arteritis SOME LITERATURE - ON VASCULAR CONDITIONS AFFECTING THE PUPILS - YEAR AUTHOR CONDITIONS YEAR AUTHOR CONDITIONS 1874 1875 1895 1908 1920 1920 (cit. Crock) bilateral carotid arteritis remote liemorrliage central retinal artery emlxilus (cit. others) aortic arcli synarome central retinal arter.i:: emlxilus traumatic extracranial carotia tliromlxisis --.intracranial embolus central rettnal artery embolus 1958 1959 1959 1959 vertebral occlusion (neck maniEulation l cerebral vascular insufficienc:i:: cardiac arrest &other acute +of BP retinal artery occlusion ( arteritis, improved by ATCH) retinal aetachment surgery (monke.)'.) occlusion of aortic arch, extracranial carotid & vertebral arteries acute blood loss & hypotension in bilateral neck dissection severe dysautonomic synclrome with hypotension retinal detachment surgery 1923 1927 1927 1927 1927 1940 1947 1957 1949 1950 --1950 1951 1952 1952 1952 1953 1953°" Schmidt Samelsohn Lacqueur Taka.i::asu Dunn Stierlin & Me:i::enburl?, Duverger & Barr6 Claude QEEin Raeder Walsh & Goldberg Tahar Walsh Wiedersheim Hollenhorst & Wagener Miletti Falls &al Hyslop SkiJ:!~r & Flint Walsh & Smith Baka_y& sweet Courville ms Ross &Mc KusicK Kaplan & Walker Leo Lmdenberg 1955 Thiebaut 1955 Wilson & Irvine Cordier & al. Finck Silverman & al. Murray Stucchi & Bianchi Blegen 1953 ~ 1955 1956 1956 1956 1956 1956 1957 1957 1957 1957 He;i::denreich Ostler Tatlov & Bammer Walsh 1960 Barbizet Hoy:! Lindenberg ParsonsSmith Dowling & Smith Martin &al. (probably) traumatic carotid occlusion (cit. Knox) central retinal artery occlusion bilateral carotict tnromoosis 1960 Milner 1960 Shy &Drager air embolus --1961 (pneumothorax) air em bolus (pneumothorax) air embolus, arteriogram, ventriculogram, trauma, h.l.'.J2otensivecrisis air em bolus !Eneumothorax) remote heinorrhage (n . r.) internal carotid occlusion arteriogram !angiosEasm) traumatic occlusion of neck arteries (includin~ neck maniEulation) pulseless isease thrombosis after internal carotid angiogram carotid and vertebral occlusion liypoxia: nitrous oxide, Co poisoning, epi sodes of respiratory embarrassment at birtb, anoxemiaduring surgery, strangulation, circulatoryfailure, lungdisease, etc. aortic arch s_yndrome cerebral angiogram (vascular spasm) aortic arcli syndrome (post. cerebral) arterial compression by increased IC P or c irculator_y failure air embulus during childbirth or attemEted abortion ischemic iris & ciliary body by retinal detachment surge!',Y air embolus (pneumothorax) arteriogram with diodrast vertebral angiogram vertebral tliromlxis1s after blunt necK trauma EOM muscle transpositions -+ iris sector depigmentation surgical error --. air embolus during vertebral angios:!am pulseless disease Eulseless disease spinal anesthesia -+ vertebral artery occlusion pulse less disease & other causes of ischemia 1960 1961 1962 1962 1962 1963 1963 1963 1964 1964 1964 1964 1965 1965 1966 1966 1966 1967 1967 1967 1967 1968 1968 1968 1968 1968 1969 1969 1970 1970 1970 1971 1971 1973 1974 1980 Boniuk & Schlesinger Mones &al. Currier & al. Hedges Weinber~r & al. Jains & QrQV!i) Paillas & al. Seitz Hedges Houck & al. Torti Wold & Leira Knox Laoouge Fisher M~nin &al. Tereao & al. Crock Labaufe Milan - JosiE Yamada &al. Davis & al. Kearns Meadows Sabah Thomas &al. Little & al Walsh & Ho~ Bi~r~e&a. Lockshin MaEstone Clevelana Rose & al. Chutkow & al. Schiffter & Schliack Bell & al. Gladstone basilar arter_y occlusion vertebral thrombosis internal carotid occlusion cardiac arrest ( cortical blindness ) (cit. Knox) pulseless disease vertebro-basilar insufficiency blunt head trauma, tearing retinal arter.i:: aortic arch s~drome ( traumatic ) carotid thrombosis blood loss & • BP in bilateral neck dissection blindness after hemorrhagic shock ( no pupil note ) iscliem1c ocuiiir 1iilla=aHon stenos1s oI Iiirge vessels in tlie necK carotia occlusion air embolus (abortion; no EUEil note) Eulseless disease ant. se~ent iscliemia (various causes) "subclavian ~teal" S,Y!!drome Eulseless disease !traumatic ) carotid thrombosis tem~ral arteritis (cit. Cobb) carotid arte!:Y occlu&ion ( giant cell) arteritis ( vertebral & carotid) caraiac arrest chronic resEirato!1'. insiilliciency {traumatic l thrombosis of int. carotid various causes of cerebral &ocular ischemia chronic reseiratory insutticienc_y temooral arter itis carotid occlusion ( ocular thermo~raEh,Y ) cardiac arrest carotid & vertebral occlusion retinal ischemia because of bilateral neck dissection carotid ➔ middle cerebral occlusion giant cell ru:t~riti§ temooral arteritis I afferent def,-~• I 1980 1957 .. ICP; intracranial pressure; EOM; extraocular muscles; BP; blood pressure. Additional cases are described on carotid occlusion, and on the "Barre- Lieou" syndrome and respective Tables. rn the chapter on trauma, 44. Vascular Conditions the patient was first seen after the operation. They failed to react to light and to attempted near vision. One month later a sluggish reaction to near vision and to lid closure had developed, with no light reflexes and no response to instilled 2% mccholyl. Four months after that the left pupil (with the smaller pupil) failed to dilate to 1% paredrine drops while the right pupil did so readily, proving that there was a left-sided postganglionic Homer's syndrome. This was attributed to the neck surgery. [n addition, there was bilateral optic atrophy, and a tonic pupil on the right side (with the larger pupil), established by right-sided pupillary contraction to mecholyl, which was absent on the left side. Both pupils contracted to near-vision efforts, the left one better than the right (tonic) one. Some cases in the literature with the vascular pathology described in this section arc summarized in Table 44-20. Peripheral neuro-vascular defects also may or may not bring about pupillary disturbances. Thus, iris rubeosis due to diabetes goes with poor, sluggish pupillary responses; but diabetic ophthalmoplegia, due to occlusion of small nutrient vessels to the intracranial third nerve, usually leaves the intraocular muscles normally reactive. Some cases with traumatic or other hemorrhages into the optic nerve (Gonin, 1903) or the third nerve (Gibson and Turner, 1987) and with corresponding afferent or efferent pupillary deficit have been / 1551 described. Patients blind due to giant cell arteriti or other ischemic disease have afferent pupillary loss. In rare cases, the third nerve or ciliary ganglion are damaged by these vascular diseases. (Davis, Daroff, and Hoyt ( 1968) saw an interesting patient ~ith _temporal arteritis who had internal ophthalmopleg1a with sub equent progression to a tonic pupil syndrome. This 69-year-old woman was admitted with_ a cough, malaise, anorexia, weight loss, P<?lymyal~ta, and polyarthritis. Her erythrocyte-s_ed1mentat1on rate was raised, and biopsy of the nght temporal artery showed giant-cell arteritis. The patient had recently noticed that her right pupil was enlarged. She had right internal ophthalmoplegia, with the pupil fixed to light and to near vision, while the smaller left pupil reacted normally. Her general symptoms improved on treatment, and the right pupil became somewhat smaller; but the pupil still refused to contract to light, and instillation of 2% methacholine chloride remained without effect. When the patient wa seen again about 18 months later, the right pupil (but not the normal left one) constricted to mecholyl, although it remained unresponsive to light and to near vision. As a counterpart to these cases, Tuckett (1905) and Sears and collaborators (1974) proved in experiment on rabbits that Homer's syndrome may develop from occlusion of nutrient vessels for the cervical sympathetic nerve and the superior cervical ganglion. F. Essential Hypertension Not much of value can be found in the literature about pupillary behavior in essential vascular hypertension. Those who favored the old vascular theories of iris motion thought hypertension would tend to cause miosis because they assumed that increased blood pressure contracted the pupils by turgescence of iris vessels. This theory was amply disproven, as described in the physiologic section of this book. Wilbrand and Saenger (I 922) expressed the generally accepted view around the first quarter of the present century that a possible influence of systemic blood pressure upon the pupils must take effect by a neural rather than by a hydraulic mechanism. Wiener and Wolfner (J 915) described a "reaction of the pupil, strongly suggestive of arteriosclerosis with increased blood pressure." This phenomenon, later dressed up as "Wiener and Wolfner's sign," was said to be pathognomonic for hypertension. It was said to consist of somewhat large pupils, relative to the patient's age, with good contractions to light which gave way to redilation prematurely, while the light stimulus was still present. This description could fit (l) the pupillary "escape" phenomenon seen in patients with afferent deficit, or (2) the premature pupillary redilation after contractions to light shown in W-typc responses, due to increased central inhibition. Without records of the pupillary movements, and without knowledge of the experimental conditions, it is impossible to decide which of these two reaction patterns Wiener and Wolfner's patients showed. Neither of them is pathognomonic of either arteriosclerosis or of vascular hypertension, although both can occur in this disease: an afferent defect could be the consequence of hypertensive retinopathy, as was described in monkeys experimentally rendered hypertensive by Gardner and co-workers (1975). These animals had reduced light reflexes and extensive damage to their retinal vessels, ending in advanced fibrinoid necrosis. And increased central inhibition indeed occurs in patients with severe hypertension early in life. In our group of 119 patients with essential hypertension we found a low incidence of pupillary defects except for those related to the central inhibitory system. Besides the relatively young patients with severe hyperten- 1552 / V. Pupillary Pathology:Pupillary Signs in Various Diseases Table 44-21. The relative frequency of pupillary defects in patients with essential hypertension PUPILLARY DEFECT Consensual Deficit Argyll Robertson Soastic Miosis 3rd Nerve Deficit Svmoathetic Deficit "Dazzling" Syndrome + Central Inhibition ., Central Inhibition ,W, Central Inhibition w- or v-Reactions Normal Pupils UNSELECTED # % 520 (28 .9) 68 ( 3.8) 74 ( 4 .1) /10.3\ 185 124 (6.9) 41 (2.3) 342 (19.0) 460 (25.6) 483 (26.8) (7 .6) 136 (8.6) 154 HYPERTENSIVE # % (22.7) 27 0 0 2 (1.7) 0 0 (7 .6) 9 1 (0.8) <7.El) 9 42 (35.3) 66 (55 .5) (15 .1) 18 0 0 RELATIVE FREQUENCY 0.79 0.00 0.42 0.00 1.10 0.35 0.40 1.38 2.07 1.99 0.00 The total number of unselected cases was 1800, that of hypertensive patients 119. Relative Frequency means the percentage among hypertensive patients divided by the percentage among unselected cases. sion just mentioned, who had pupillary signs of increased central inhibition, the rest of the patients had moderate or complete loss of inhibition, or the "diencephalic-mesencephalic" reflex pattern of small, rather sluggish w- or v-shaped reactions (Table 44-21). Partly this trend may be related to the patients' age. As a group they were older than the unselected clinical population used in these statistics (53 years and 37 years, respectively). But it should be noted that none of the hypertensive patients had entirely normal pupils in this respect, although many of them were not old.