Chapter 23: Special Oculomotor Syndrome

23 CHAPTER Special Oculomotor Syndromes CONTENTS I. "Misdirection Dyskinesia (or Synkinesia)" A. Appearance .................... 8. Mechanism .................... C. Clinical Course . ................. II. "Abduction Miosis" ................. A. Appearance .................... B. Mechanism .................... Ill. Oculomotor Paresis with Cyclic Spasms ... A. Summary ...................... 8. Historical Background . ............ C. Appearance .................... 1. Clinical History ............... 2. Onset ...................... 3. Sensory and Motor Impairment .... 1048 1048 1054 1054 1055 1055 1056 1056 1056 1057 1064 1064 1065 1067 4. Spastic Movements ............. 5. Influence of Attempted Eye Movements on Cyclic Activity . . . . . 6. Influence of Physiologic Conditions and of Drugs . . . . . . . . . . . . . . . . (a) Sleep, Arousal, Physical or Emotional Stress, and Systemic Drugs ................... (b) Drugs Instilled into the Eye .... 7. Clinical Course . ............... D. Localization of the Lesion and Mechanism of the Syndrome ........ 1. Historical Views ............... 2. Probable Site and Mechanism ..... 1067 . 1072 . 1072 1072 1074 1074 1074 1074 1076 I. "Misdirection Dyskinesia (or Synkinesia)" A. Appearance After intracranial interruption of the third nervemost often by trauma or aneurysms, and sometimes in patients with tumors or ophthalmoplegic migraine-a phenomenon develops that has given rise to much controversy in connection with the Argyll Robertson syndrome. --R------L--. <® a ~ ~ ~ b~~ ~++ • ~ C 4!2>+-~ d ------~ ➔~ ~t~ ,~ f ~ 1048 ~ From about 2 months to a year after the acute stage of oculomotor palsy, some of the eye movements recover gradually. The initially large and fixed pupil may begin to become smaller even sooner. The light reflexes rarely improve, but after some months pupillary contractions to near vision often return and may in time become quite extensive. The resulting "light-near dissociation" was thought to be a "traumatic Argyll Robertson" syndrome, and to prove that Argyll Robertson pupils can result from postnuclear third nerve lesions (Table 23-1). However, there are important differences between this syn- Figure 23-1. Diagram of "misdirection dyskinesia" after oculo· motor paralysis on the left side. R, right eye; L, left eye. At straight ahead gaze (a) the lid tends to droop and the pupil is large. With every movement that calls one of the branches of the left third nerve into play, that is, on convergence (b), on lateral gaze to the right (c) and on attempted upward and downward gaze (e and O,the eye moves nasally, the lid lifts, and the pupil contracts. On conjugate gale to the left (d) the left third nerve becomes inactive so that the eye drifts temporally, the lid droops and the pupil redilates. Upward and downward movements of the globe are absent because of co-contraction of the vertical recti. Comment: In this diagram a complete initial lesion and diffuse re-innervation of all muscles supplied by the third nerve have been assumed. Most cases are less complete: some physiologic movement may be retained, and the pathologic re-innervation may affect one muscle more or less than others. All kinds of combinations of normal and abnormal movements may thus be seen in such cases. The pupil usually becomes smaller with time. This is probably due to the fact that third nerve fibers to extraocular muscles fire spontaneously, even in the absence of overt movement. When such fibers invade the ciliary ganglion, they will stimulate the postganglionic pupillary fibers. 23. Special Oculomotor Syndromes / 1049 Table 23-1. Patients with misdirection dyskinesia after damage to the third nerve (cases with questionable diagnoses omitted) YEAR AUTHOR CASES 1879 Gowers #1 1885 1890 1893 Jessoe Browning /Fuchs) #1 Fuchs #2 w-- -~ Brautigam Abelsdorff Weste Guillain &Houzel Guillain & al Franke Reiche Finkelnburg Bielschowsky Fuchs Bauer Meyer Kafka Samaia Bielschowsky 1923 Guillain & Laederich Matz·dortt Marauez n HauEtvogel Sattler Behr Boente Cords Bielschowsky Abramovicz Heard & Abramson Rugg-Gunn Terrien & Du12u:i:-Dutem12s Aliguo-Mazzei Roemheld Bielschowsk:i: Bollack Feuillade Harris 1923 1924 1925 1925 1926 1927 1929 1932 1933 1933 1933 1933 1934 1934 1935 1935 1935 1935 Sy u TERM USED, AND REMARKS partial 3rd nerve palsy ( lid only) + + + + + + + 0 + + Eeculiar anomaly of pupils (citecl 5y Fuclis l 37 "cases" ? 3 4y d'26 a' 9 traumatic cavernous fistula skull fracture cf 63 ? tumor in middle fossa u u u u u u u u u u u u u u u u u 6"55 "ff' 3 a'? several -g..:!!.._ 27 33 ~ 55 a' 33 cf' 18 ~ TIME 0 o"6o 1906 1908 1908 1909 1909 1912 1913 1914 1916 1917 1918 1920 1921 1921 1922 L 19 V ? 1V 10 y ? 3m alist• 8m years ? months a"ns 1898 1899 1903 1906 1906 - years cf 56 ¥5 Katz KrUrrer Fuchs Friedenwald #1 Brixa #2 Solder Bregman Raecke Abelsdorff Axenfeld #1 CAUSE B skull fracture congenital u svnhilis u u s:i:Ehilis u conrnitaI u sye ilis 3rd nerve oalsv u bas al fracture u congenital u 1 sy)2hilis, 1 stroke u probably aneurysm u stab wound through lower lid u u erobabl:t: aneur:i:sm skull rracture u gun sliot in R temple u heacl trauma u basal fracture u trauma u (aneurysm ?) u head trauma u u trauma shot in the head u u stroke bas al fracture u head trauma (ex12losion) u head trauma u basal trauma I tumors, s:i:Ehilis u head trauma u u S:i:Ehilitic 3rd nerve Eais:i: strucK by !iglitning u u S:i:£hilitic oEhthalmoplegia skull fracture u (aneurysm ?) u treated svohilis u head trauma with u hemorrhage shot in temEle u traumatic cavernous fistula u head trauma u congenital svohilis u basal (surgical) trauma u head trauma u shot in the head u summary (no cletails) post-measles 3rd nerve palsy u ~ ns -(fns #4 1894 1894 1895 1896 1898 ---ns ns -&;~ 45 g. 20 nr 6"26 -&.2859 ? a' 51 several ? ns 6"42 6"35 cf 55 ~49 - (!'33 cJ'45 ~36 30 30 15 g,, 1 3: 40 42 oculomotor paresis skuU fracture skull fracture· "many" 3rd nerve pals:i: lieacl trauma 6"68 CJ" 28 trauma and hemorrh~e basal skull fracture ns abnormal associated movements; perhaps nuclear defect; (lid movements described) 0 0 0 0 0 + 0 0 0 0 0 0 + + + 0 0 0 + + abnormal association movement unilateral reIJex rigidity .. anomalous co-movement associated movements pupil and lid involved lid only lid only Argyll Robertson synarome (traumatic) Westphal-Piltz phenomenon traumatic Argyll Robertson traumatic retlex rigiaity reflex rictditv (traumatic) reflex rigidity traumatic Argyll Robertson unilateral light rigiditv Argvll Robertson syndrome Argvll Robertson svndrome unilateral retlex rigidity unilateral reflex rigiditv traumatic Arg:i:ll Robertson aberrant fiber regeneration pathologic co-movement Argyll Robertson after oculomotor palsy "true Ar<rv Robertson unusual pupil finding non-syphilitic Argyll Robertson abnormal EUEillar:i: co-movement abnormal pupillarv co-movement 0 traumatic unilateral Argyll Robertson 0 0 + + 0 0 + + unilateral traumatic reflex rigiditv 122st-traumatic Arg:i:ll Robertson pathologic co-movement pathologic co-movement oseuao-traumatic reflex rigidity traumatic (pseudo) reflex rigrnny peculiar pupil!ary plienomenon alierrant regeneration asynergic lid co-movements ( lid only) ? 6-7 m 0 + "Argvll Robertson" traumatic Argyll Robertson ly 0 Argyll Robertson m l.5y years 13 V llm ns 0 0 + + 0 0 ? ? + + ? 3w years ly ns ns ns 3;\'. nr 3m montlis ns 1, 5 :t: 3 w- 6 m variable ? ns 6m 5m 15 :t: 6-8 m 2 :i: 6m 0 3V ? months ;ears .5 m 4.5 y 20 y - - unilateral Ar!Q:ll Robertson after trauma oseuclotalies traumatica aberrant regeneration Arg:i:ll Robertson with lid seasm unilateral Argyll Robertson after trauma Argyll Robertson as late effect of 3rd nerve oalsv basal fracture at age 2 1936 Aliquo-Mazzei #1 abst* 0 Ar!Q:11Robertson Q 36 a5si• basal fracture Argyll Robertson i2" -o' 37 0 #3 head trauma abst* 0 Argyll Robertson 9 72 ns basal fracture 1936 Bielschowsky #1 months + abnormal co-movement t2 ns basal fracture 15 m + abnormal co-movement 20 1936 Bender tumor comeressing 3rd nerve slow + fault1 regeneration (Eseudo-von Graefe) 1937 Bender & Al~rt rs- ruotured aneurvsm + fault.)'. ~riEheral re-innervation 6.5 ,l'. 1937 Sprenger abst* head trauma abst* + adduction miosis and Argyll Robertson ouoil 1938 Ford & Woodhall cJ'38 basal fracture + misdirection of regenerating fibers u 7y o"3& basal fracture 1939 Bielschowsky ltl + misdirection of regenerating u ? #2 28 unknown cause u 5m + fibers 24 1935 Igai ( birth trauma ? ) u 24 y + abnormal pupil reaction '"T§IT" BUrki aneurysm a'~ no term used u 11ly 11 0 '"T§IT" Ferrante abst* basal fracture u long 0 Arg:i:11Robertson -+ Adie's eu12il 1941 Ford, Walsh #2 cf 58 bleeding aneuri::sm + Argyll-Robertson-like u 6-9 m movement #3 &King anomalous vessel u 1y + aue to misairection of regenerating 41 20 7M aneurysm u 5m + oculomotor nerve fibers ns - informat10n not provided m publlcat10n, nr - not read by reviewer, ? not available for one of these reasons; abst* = mformation not given in abstract; in CASES, numbers marked# are case numbers given by authors, and numbers without symbol mean number of cases described without individual detail, The terms used for the condition indicate the authors' opinions about the mechanism responsible for the pupillary defect. For further symbols, see part 2 of this Table. 8 g. g,, --8 Table 23-1 YEAR 1942 1942 1945 1946 1947 1947 1948 1948 1952 1952 1953 1956 1956 1957 1957 1957 1959 1959 1963 1964 (continued) TERM USED, AND REMARKS AUTHOR Sy TIME CASES CAUSE L cf'? Nathan & #1 skull injury lu 5-6 m 0 Argyll Robertson Turner ns ~ O"'? skull fracture ~ misdirection syndrome Walsh & King #9 + d" 58 bleeding aneurysm u ns Bender #1 0"'20 + skull fracture u 10 w + synkinetic pupil phenomenon #2 cf' 23 sw skull fracture B + #3 Cl"'50 u ? s:y:ehilitic oehthalmoelegia Wartenberg #1 Cf 23 skull fracture 0 u 21 m central "release phenomenon" ~ ~58 0 syehilitic third nerve palsy u 10 y /see Chanter 11\ 40 #4 0 syehilitic thircl nerve ealsy u 3y abnormal associated movements Christini #1 + 50 u 10 m aneur~m co-movement of lid and pupil Schretzmayr #1 + ~? shell - agment u 5m -cf' 19 ~ + grenade splinter & fracture u 6m rt' rgRussell & Wright + aberrant regeneration skull lracture u OS Walsh 2 pts + aberrant regeneration aneurysm u months l'aulty regeneration ( ha) Hugonnier a"n+ ns u 9m Levin aEierrant regenerafton ( anatomy) 67 + insidious int. carotid aneurysm u ::> '7 y Norton & Wetzie: 4m + aberrant regeneration ~ 50 trauma & subdural hematoma B Cogan a" 17 + aberrant regeneration birth trauma u 17 y Leonnara 31 patnologic co-movement + skull tracture u 3y Tnilibaut & 61 Argyll Robertson stroke 0 u 3y Matavuli Walsh summary on (misdirected) 3rd nerve regeneration (6 cases & statistics on 42, comparea to 4 patients with diabetic oculomotor palsy without misdirection) Walsh & ns + Argyll Robertson-l1ke m1sctirect10n bleeding aneurysm u ns Breinin + a" ? skull fracture ~ndrome ( electro -myogram) u 4m Forster & al a rrant regeneration ? + aneur:i:'.sm ? ? Guillaumat & al no term used ns 3rd nerve palsy u ns 0 Johnston & PrattJohnston #10 o" 39 aneurvsm + u 6y aberrant regeneration #12 -g..27 + h!lad trauma u 4 :i:'. Holland + 31 basal fracture u 3y mirs\f&'i-~<2!h?blt~ erating fibers u- 8w c; 9 1965 1966 1966} 1967 Smith & Smith Sussman 1969 1969 1971} 1973 Walsh & I-IO;):'.t Forster & al #1 #2 Mukuno & al Oono & Mukuno 1972 1974} 1974 1977 Schellenbeck & al Gra;):'.son & al Soni Miller Hepler Schatz & al 1978 Czarnecki Thomeson Trobe & al #3 1979 ~ 10 cases 36 99 4 30 cases cf #1 35 -w-- -a"~ #3 _Q_5_1_ «~4 53 & cases Cl"'54 ~ -(]¥ 72 Boghen & al #1 #2 ~g ~ =19 40 #-4 1979 1980 1980 Kerns & al O'Da;i & al Lepore & Glaser - ? ? + head trauma + u 3m survivors of internal carotid aneurysms with third nerve + u aver.= 6.7 y oalsv misdirected or not Ion on oculomotor regeneration, + 3rd nerve ealsy (? cause} u 5w 12 y + vascular malformation B head trauma, aneurysm, basal + various u meningitis, syphilis, tumor, congenital tem~ro-basal chondroma + u 1y + aneu!:l:'.sms post.comm.artery u various + intracavernous meningiomas u 3-18 m isolated 3rd nerve palsy: + trauma, tumor, infections , u various aneurysms, opthalmoplegic migraine meningioma in cavernous sinus u lv + + or in cavernous sinus and u 5y + u 2-3 m } middle fossa + u < 19 m 9 aneurysm, 3 trauma, 1 tumor + u ns 1 congenital + cavernous sinus meningj,oma u ? + intracavernous aneurvsm u ? + cavernous sinus meningioma u 4 :i:'. + lateral fossa mening!oma u 4y + cavernous sinus mening!oma u 2y + cavernous sinus meningioma u 17 y + aneurysm of e2st. cerebral a. u 10 m + u years "oehthalmoelegic migraine"* + u 3y "oehthalmoelegic migraine"* + cavernous sinus meningioma u 9y + intracavernous aneurysm 'fJ 2y nr 15 5 cases (aver. = 58 .6) summar, 0"'15 9 34 & Cantu 1977 1978 nr 58 57 45 #1 ~ 3 ~ -cf' 69 ~ 7J'72 1 ahP.rrant regenerat10n 01 oculomotor misdirection of regenerating fibers aberrant n. regeneration 256-260\ third nerve misdirection ( aberrant regeneration) misdirection syndrome palsy in oculomotor aberrant regeneration aberrant regeneration misdirection syndrome aberrant regeneration primary aberrant oculomotor ration with insidious onset aberrant re gene - regeneration insidious onset of aberrant regeneration without oaralvtic oh""" primary aberrant regeneration of injured oculomotor nerve fibers, without paralytic phase sli1rht misdirection /lid\ aberrant regeneration erroneous theory (see text) pseudo von Graefe phenomenon * We also have observed such a case: a 62-year-old man with a life-long history of ophthalmoplegic migraine, with regular bouts of pain and occasional paralytic episodes every few years. At first his eye movements had recovered fully between paretic attacks , except for the pupil, which remained enlarged. Later the paresis became permanent , with periodic worsening. At the time of examination his headache attacks had almost subsided. In darkness his affected pupil was smaller than the normal one and slightly distorted. It was fixed to light but constricted briskly on convergence and on lateral gaze with the affected eye adducted. It then became very small and round. The symbols mean the following: In column L ( for laterality) , U means unilateral and B, bilateral; in column Sy, + means that synkinetic pupil movements were observed, and O that they were interpreted as dissociated Argyll Robertson reactions to near vision ( that is, during convergence, without testing of conjugate eye movements) . In TIME, the weeks (w), months (m), or years (y) that elapsed between the acute onset and the time of examination is indicated. Note that in a few cases with slowly expanding lesions there was no acute phase of paresis; instead, small numbers of injured fibers sprouted insidiously over months or years before the condition was recognized. ADDITIONAL REPORTS 19§1 1 Spector & Faria: patient with inferior division of 3rd nerve regeneration; 1983, Lotufo & al. : 4-year-old child with congenital misdirection syndrome: affected pupil was smaller than normal, especially in dim light; 1984, Olsen & Jakobsen: misdirection in a case with congenital oculomotor palsy; 1984 1 Parker & Biefang: aberrant regeneration, with 3rd and 4th nerves involved; 1984, Olsen &Jacobsen: abnormal pupillary function in third nerve regeneration (pseudo-Argyll Robertson); 1986, Cox: sector regeneration as first sign of acquired oculomotor synkinesis. 1050 23. Special Oculomotor Syndromes drome and the Argyll Robertson syndrome. First, the Argyll Robertson syndrome is typically bilateral, but this syndrome is almost always unilateral; and second, in the Argyll Robertson syndrome only the pupil is involved, but in this group of patients the extraocular movements also are abnormal: in complete, typical cases there is partial ptosis, impaired adduction of the globe, very poor or absent vertical eye movements, and defective accommodation. On this background of paresis there are extensive involuntary movements: each time the patient tries to adduct the eye or look up or down, the lid snaps up, the globe wanders toward midline, the pupil contracts, and accommodation increases (Figures 23-1 and 23-2). Further, the pupil may change its shape on attempted movements of the globe (Czarnecki and Thompson, 1978; see Figures 23-3 and 43-2, and Table 23-2). These distortions are due to re-establishment of innervation of ciliary ganglion cells that serve segments of the pupillary sphincter by fibers that formerly had run to extraocular muscles. This occurs more frequently than was appreciated in the past because innervation of small sphincter segments may leave the pupil nearly round. But when looked for with the slit lamp or with enlarged photographs or motion pictures, it can be clearly seen that an attempted eye movement in one direction will bunch up the iris tissue by contraction of a Figure 23-2. Pupil and lid movements in a patient with "misdirection dyskinesia" after rupture of an internal carotid aneurysm. At the time of examination the patient was 34 years old. She was married and had a 2-year-old child. She had never been seriously ill but had had intermittent headaches all her adult life. These were thought to be migraine. About a year before examination the headaches had become worse. When she looked to the left, her left eye "twitched." One day she had a bad headache above her left eye. It became worse and worse, and after 2 days and a night without relief her left lid was almost closed. She was sent for skull X-rays which were negative. Two days later she suddenly felt "something give way in her head" and collapsed with an intracranial hemorrhage. A ruptured aneurysm of the left internal carotid at its bifurcation with the posterior communicating artery was found and clipped. Postoperatively she had total left third nerve palsy and right-sided hemiplegia with aphasia for 2 weeks. These signs cleared gradually. Eye movements also returned partly, with misdirection dyskinesia: adduction was limited and vertical eye movements (especially elevation) very poor. On straight-ahead gaze her left pupil was slightly smaller than the normal one in darkness, and it failed to react to light, both directly (B) and consensually (A). It contracted to near vision, but less so than the normal pupil (C), while psychosensory reflex dilation was as good as in the right eye (D). The left pupil contracted slightly when the patient tried to look up (0.5 mm, in E), and more so on attempted down-gaze (1.2 mm, in F). When she tried to look to the rightwith poor adduction of the globe-the pupil contracted even more vigorously (2 mm, in G); and wher. she abducted the left eye during left-gaze the pupil dilated slightly (0.3 mm, in H). The simultaneous lid movements are shown for horizontal gaze (dash-dot) lines in G' and H', showing the width of the left palpebral fissure in mm): attempted adduction of the globe caused the lid to go up 2 mm (G'), and during abduction it drooped strongly (H'). Note that the striated levator palpebrae contracted and relaxed much faster and with a shorter latent period than the smooth iris sphincter. / 1051 small segment of the sphincter, and an attempted movement in the opposite direction will smooth it out again (Figure 23-3). Czarnecki and Thompson found this in seven of fourteen patients who had recovered from oculomotor palsy due to various causes (Table 23-2). Another interesting detail observed by these authors in nine of their fourteen cases was constant ipsilateral oscillations of the pupil. These were not the normal fluctuations of pupillary unrest that appear during light exposure. These pupils were fixed or reacted only poorly to light; and the oscillations were the same in light and in darkness. In contrast, normal pupils are quiet in darkness, and the rate and amplitude of light-induced unrest vary with the intensity of stimulation. Further, the pathologic pupillary oscillations did not coincide with movements on the normal side (Figure 23-4). It should be emphasized that asynchrony of the two pupils' normal "unrest" oscillations never occurs. Residual supersensitivity to drugs such as mecholyl or pilocarpine (if at all demonstrable) can be expected to be slight in such cases, first, because preganglionic lesions cause only mild "decentralization" type of supersensitivity, and second, because re-innervation and supersensitivity are inversely related (sec Chapter 11). :=i9=--== :---------~ 31--~--l-------~31-------1--~--==--------f I Z.r. 2 61-E-A~ I _._•~-J6LL~F~==~=!='==d~ow=n====::l:=:= _____ --1--------------1--~,--..,.-D--_.__J 6 1--G l. l. 2. s ----~•l•---- +--~------~·-.....,_:c=----t--c::-~..--; -------; H-----------~ ---------16'-- t----=~=-=·-i'~,-,,--------1 s1----------,--- L-----'-~--~-----l ~l------i--------4 1-----i-!_ 0,/Set!.-+ i;,--- '~------ !•addud t 3l-------i!"!!¢1===a=b=d=u=,:;=t ! -- ==t►-~ 1052 / IV. Pupillary Pathology:Symptomalogy Table 23-2. Patient Clinical features of patients Origin of Third-Nerve Palsy Light Reaction Gaze-Pupil Sector Contractions Hippus Yes 1 Aneurysm No Yes No Yes Yes None or minimal Yes 2 Aneurysm 3 4 Aneurysm Congenital No Yes (sectorial) Yes No 5 Aneurysm Yes No Yes 6 Trauma Yes (sectorial) No Yes 7 Aneurysm Yes No Yes 8 9 Aneurysm Yes (sectorial) Yes (sectorial) No Yes Yes None or minimal 10 Aneurysm No No No 11 Trauma Yes (sectorial) 12 Aneurysm Yes (sectorial) Yes No Yes Yes 13 Aneurysm Yes 14 Tumor Yes (sectorial) No None or minimal No Trauma Yes From Czarnecki and Thompson,Arch. Ophthal. 96(1978):1606 Attempted Upgaze Primary Position Attempted Downgaze Figure 23-3. Segmental contraction of the iris sphincter with eye movements in a patient with misdirection dyskinesia (case 3 of Table 23-2). The patient had had third nerve palsy due to an aneurysm on the right side. The pupil was fixed to light and almost quiet at medium size in darkness. In the primary position it wa round. Upon attempted upward gaze, segmental sphincter con- traction developed at 4 to 6 o'clock. while the iris tissue relaxed between 11 to I o'clock. Upon attempted downward gaze the opposite occurred: there was contraction at 12 o'clock and relaxation in the 4 to 6 o'clock areas. (From J.S.C. Czarnecki and I LS. Thompson,Arch. Ophtha/., Chicago, 96 [1978]:1606; 1978, American Medical Association) 23. Special Oculomotor Syndromes / E 6 .s I< •ISarkness 1053 > [19fit ~ .; Right Eye E cu 5 i5 i':' ~ ·c. :, Left a. 4 Left Eye 3 Time (sec) Figure 23-4. Pupillary movements of a patient with misdirection dyskinesia after left oculomotor palsy. In darkness (left side of graph, as marked) the normal right pupil was quiet. The affected left pupil was smaller and showed constant. small oscillations. This pupil failed to respond to light but instead continued its oscillatory behavior unchanged in darkness and in light. The normal ..... A B pupil had a brisk contraction to light, followed by irregular pupillary unrest. Co111me11t: Note that this unrest and the left pupil's oscillations were not synchronous. Normally the rhythm of pupillary unrest is identical in the two eyes (sec Chapter 3). (From J.S.C. Czarnecki and 11.S.Thompson,Arch. Ophthal., Chicago, 96 [ I978]: 1606; • 1978, American Medical Association) ~ ,,. !lll11llllitllllf ll-1•• •11111•~--~---· ~ -"' - - ~ levator palpebrae ~ ~ "' ? (@' .... ,... @ I STRAIGHT +-- -- --- ~~ ,~ • I (~ ~tur a:"'::ur i.+- ' E D C - - -....., -e--- _,, --..... --~---•1levator palpebrae medial rectua ~ ~ c~~~~ - t , --+ ••,.llf.-..•~ '" } __ ~ ,,,1//1}~'>'-~~ \ , ,,,;,._\ )la..- ~/ ~"\_J~ --- ' ,i~•-··. ,'-~'. ) ( ~ \ superior rectua ,.,1-.uut11• •• • 1t11111, Inferior rectua Figure 23-5. Electromyographic discharges from the left eye of a patient with oculomotor misdirection syndrome. The arrows show attempted direction of gaze. Action currents were obtained from the medial rectus, superior rectus, inferior rectus, and levator palpebrac, as indicated. Note the decrease of firing in all channels when the left eye was abducted (from B to C), and the vigorous increase of discharges on attempted adduction (A), upward gaze ,,, ,h zs• I Inferior rectua (D), or downward gaze (E). The left lid was flaccid in the primary position and in left-gaze (Band C). Upon attempted adduction (A) and (less so) in up-gaze (D) it lifted spontaneously, and during down-gaze (E) it failed to descend as did the normal right lid (held up by finger). (Drawn after photographs from G. Holland, Klin. Mb!. Augenheilk, 144 [ I964]:686) 1054 I IV. Pupillary Pathology: Symptomalogy B. Mechanism The reason for this strange combination of movements was shown by the work of Cajal, 1913, 1928; Bielschowsky, 1916, 1922, 1939; Bender, 1936, 1945; Bender and Alpert, 1937; Bender and Fulton, l 938, 1939; Ford, 1933; Ford and Woodhall, l 936, 1945; Ford, Walsh, and King, 1941; Walsh, 1948, 1957; and later authors; (see Table 23-l ). Just as happens in other motor systems, a damaged third nerve regenerates. Surviving nerve fibers send new axon sprouts across the scar into the peripheral nerve tubes (sheaths of Schwann). This kind of regeneration is disorderly: some of the severed Schwann sheaths in the distal stump of the nerve do not receive any new axons, while others are invaded by fibers that travelled down other regions of the proximal portion of the nerve. These new axons were jumbled up in the scar, and therefore grew down to muscles that their original distal fibers had not supplied. In cases with extensive lesions and subsequent diffuse regeneration, all muscles served by the third nerve will receive such faulty innervation from other portions of the central nerve stump; and consequently, whenever the patient tries to move the eye in a direction that calls upon a muscle formerly supplied by one of the branches of the third nerve, the misdirected nerve sprouts carry impulses to all muscles served by this nerve in a simultaneous mass discharge. This results in the "misdirection" type of ocular movement just described. Since simultaneous contractions of the superior and inferior recti cancel one another, vertical eye movements do not occur. Adduction, lid retraction, and pupillary constriction, in contrast, are possible because the internal rectus, the levator palpebrae, and the pupillary sphincter do not have antagonists innervated by the third nerve. This mechanism is shown clearly by electrophysiologic experiments that demonstrate the abnormal firing of the third nerve branches and the consequent coinnervation of the affected muscles (Figure 23-5). This concept of the mechanism of the syndromefirmly established for many years-has been challenged off and on, based on assumptions devoid of anatomic support (Wartenberg, 1946; Lyle, 1966; Lepore and Glaser, 1980; see Chapter 11). C. Clinical Course The severity and the nature of the original injury and the degree of oculomotor regeneration after such lesions, as well as the chance distribution of the regenerating axon sprouts, vary from case to case. For this reason the "typical" misdirection syndrome is often incomplete or modified. Many different combinations of paresis and of normal and abnormal movements can be observed in different patients. The pupil is, however, almost always pathologic, probably because the pupillary fibers are especially prone to injury in their intracranial course, as discussed in Chapters 3 and 22. The pupil often remains permanently fixed. The light reflex, once it has been lost for more than a few weeks, seldom returns, and the "near-vision" contractions which may develop later are, in fact, abnormal co-movements of the pupil with the internal rectus during attempted convergence. Lid retraction during attempted adduction or down-gaze is almost always found. 1 With time, the affected pupil usually becomes smaller than the normal one (in darkness); but reflex dilation is not abolished unless the sympathetic nerve supply to the dilator muscle has been damaged by the same lesion. This happens occasionally, for example, in patients with trauma or tumors near the orbital apex. Once established, the particular pattern of eye movements in each patient appears to remain unchanged for years. The abnormal movements cannot be cured by surgery. Aside from the dangers of intracranial interven- 1. Walsh (1957) mentioned that "one of the early evidences of involvement of the third nerve at the base is the onset of ptosis, since that portion of the nerve which serves the levator muscle is particularly exposed." tion near the base, cutting the third nerve would merely result in ophthalmoplegia, followed (if regeneration occurred) by a new pattern of dyskinetic movements. Unless the third nerve axons are interrupted, faulty regeneration will not occur. For this reason the phenomenon is almost never encountered after (ischemic) ophthalmoplegia due to diabetes, or after slight bruising of the nerve. But tumors and other forms of pressure can interrupt all or some of the third nerve fibers, with migration of regenerating nerve sprouts from their proper channels. "Primary oculomotor misdirection" syndromes due to such lesions usually are not preceded by frank ophthalmoplegia; and they are subtle and of insidious onset. They often involve the lid alone. Such mild signs of misdirection appear less rare than was formerly thought when they are looked for actively (Levin, 1952; Schatz et al., 1977; Boghen et al., 1979; O'Day et al., 1980).2 According to Grayson and coworkers (1974), recovery of normal eye movements in patients with aneurysm is possible when they are treated surgically within 10 days after the injury; but with longer delays before the operation, misdirection patterns develop (see Chapter 11 for possible reasons for this time dependence). In the past, cases of oculomotor misdirection were described after ophthalmoplegia due to basal syphilitic infections. Since penicillin became available for prompt and effective anti-syphilitic treatment, this has no longer been observed. 2. Cajal described misdirection of nerve fibers injured by pressure in beautiful detail (see Chapter l l). Table 23-3. Pupillary "abduction phenomenon": Cases in the literature YEAR AUTHOR CASES 1857 von Graefe 1875 Weiss 1885 Jessop 1894 Samelsohn 1904 Bielschowsky 1921 Behr 1922 Bielschowsky 1922 1922 Blatt Kramer 1923 Salus 1924 Behr 1926 1932 1957 De Rosa Bielschowskv Pietrushka & Stumpf 1957 Walsh 1959 Morone 3 patients with unilateral 3rd nerve palsy: pupils fixed to light and near, constricted u12on al!.duction of the globe o"32, 4 years syphilis: left pupil sluggish, 3mm; right pupil 6 mm, fixed to light and slightly reactive to near; it constricted strongly when the eye was abducted cited by Behr and by Morone, but the patient had 3rd nerve 11misdircction: the 12upil constricted on adduction 6 patients: all had both pupils fixed to light and near; 5 had unilat. 3rd nerve paresis, and one unilateral 6th nerve palsy; during recovery the anomalous pupil contractions on abduction appeared o""49, 2 years after episode of left oculomotor palsy: left EOM and L pupil (7. 5-8 mm) fixed to light& near; accommodative paresis; Il. pupil (5. 5 mm) fixed to light and poor to near; L pupil constricted brisk!;):'.to 4 mm on abduction of OS and on forced lid closure. 6 patients, 5 of them luetic; all had marked disturbances of pupil reflexes, some also EOM involvement; all had marked "lid close reflex" and "abduction miosis": after about 1 second of strong .llhduction the pupil constricted rapidly and extensively; it redilated at the end of the abduction effort 1 patient: prompt contraction on ( even slight) abduction, without delay atients: prompt, extensive abduction miosis without delay 15 with congenital 3rd nerve palsy, including all branches, and proptosis; otherwise fixed pupil contracted on forced lid close and on extreme abduction o'64, tabes: diplopia & L 3rd nerve paresis of all branches; both pupils ( R 4, L 3 mm) fixed to light & near; during lateral gaze pupil of abducted eye constricted vigorously to 2. 5 mm while that of JiUlducted eye dilated to 5. 5 mm; during convergence both pupils dilated; no lidclose contraction discussion of abduction miosis: 2 cases with 6th nerve palsy (same material as 1921) 12atient with pupil fixed to light and near, contracting on abduction abduction miosis mentioned -- no new case ~ 56, syphilis for more than 20 years, signs oi tabo-pares1s; hm1ted up-gaze in both and poor abduction in the left eye; pupils in 10 gazeR2.5, L3.0mm, fixed to light; in lateral gaze the Jl.!!.ducted pupil dilated, the abducted constricted; on convergence, both pupils dilated case #5, 4 months after skull fracture, showed firing to medial rectus muscle on attempted .all.duction, but pupil was not affected: it constricted on adduction and dilated on abduction mention of "abduction phenomenon" but no new case EOM = extraocular M muscles; R = right; L = left; OS= left and OD right eye. Additional case: 1906, v. Hippe!: cf suspected of ta bes had bilateral mydriasis; on gaze L, the left pupil (abducted) contracted 2-2. 5 mm; on gaze R, the right pupil remained large. 1984, Packer & Biefang: 3rd & 4th nerve aberrant regeneration. ' II. "Abduction Miosis" A. Appearance The discovery of this rare pupillary abnormality is usually credited to Behr, but it was first described by von Graefe. We have encountered only a few reports in the literature, and have never seen a case in our laboratory (Table 23-3). All of these patients had organic diseases of the central nervous system or head trauma. The essential features of the syndrome were described as follows. There was third nerve paresis in one eye, and the pupil was fixed to light, or to light and to near vision. When the patient abducted the affected eye, the pupil constricted, and at the end of the abduction effort it redilated while the eye slowly moved back to its original position. Adduction of the globe was poor or missing in some cases because of the oculomotor damage, and the pupil remained unaffected by the adduction effort. In other cases the pupil dilated when the eye moved in, both during convergence and in conjugate gaze. There were rare bilateral cases. Behr said that a long latent period preceded the contractions, and that an unusually strong abduction effort was required to elicit them. But most other authors, for example, Blatt, Bielschowsky, and Salus, found the constriction prompt and brisk. It occurred even during slight abduction efforts. Behr also said that in all cases with abduction miosis there was good pupillary constriction on forced lid closure or a "paradoxical" light reflex; but again, this was not confirmed by others. 1055 1056 / IV. Pupillary Pathology: Symptomalogy B. Mechanism To explain the abduction miosis, several theories were proposed. They involved, first, mechanical effects, that is, traction or torsion of ciliary nerves during the abduction movement (Marina and others); second, straying of supranuclear impulses from the sixth to the third nerve nucleus because of a brainstem lesion (Behr, 1921, 1924); or third, anomalous co-innervation of the external rectus muscle and the pupillary sphincter, either after a lesion involving the third and sixth nerves (Salus, 1923), or physiologically, by congenital anomalous anastomoses between these two nerves, or between sixth nerve fibers and the ciliary ganglion (Bielschowsky, 1922; Blatt, 1922). Behr ruled out the mechanical hypothesis by demonstrating that the pupil of such patients continued to contract during abduction efforts when the globe was immobilized by forceps, so that the abduction effort did not result in an abduction movement. Behr further believed the theory of peripheral misdirection of impulses to be disproven by two cases who developed abduction miosis after damage to the sixth nerve: when they tried unsuccessfully to abduct the eye, the pupil constricted. Behr reasoned that the absence of abduction movements of the globe proved that no sixth nerve impulses existed, and therefore none could stray to the third nerve. However, we think this conclusion errone- ous: regenerating axon fibers of injured nerves often join other channels without necessarily finding their way to the effectors that they had supplied orginally. In our opinion the occurrence of abduction miosis in patients with known peripheral sixth nerve damage strengthens the probability of nn efferent misdirection syndrome for acquired abduction miosis rather than ruling it out. Such misdirection could, for example, occur in the area of the cavernous sinus and superior orbital fissure, where the third and sixth nerves run in close proximity (see Figure 22-18). In this connection, electrophysiologic findings described by Walsh are of interest (1957): in a patient with third nerve misdirection (Walsh's case 5) there was firing of action potentials to the internal rectus muscle during attempted abduction of the globe. Recently Pfeiffer, Simonsz, and Kommerell described a fascinating case of abduction miosis undoubtedly due to misdirection of sixth nerve fibers into the pupillomotor path (personal communication, 1990). The patient, a 16-year-old girl, had suffered severe head trauma 3 years earlier. After an initially total right-sided ophthalmoplegia, right third and fourth nerve palsy remained complete but abduction recovered gradually and pupillary constriction upon abduction (but not to light or to near vision) was observed. III. Oculomotor Paresis with Cyclic Spasms A. Summary Oculomotor paresis with cyclic spasms is a rare syndrome, usually noticeable at birth or developing during the first years of life. Typically there are ptosis, mydriasis, limitation of extraocular movements, and accommodative loss (Figure 23-6,A). Amblyopia is common, but there are no other constantly associated ocular or neurologic defects. On this background of paresis, spastic movements occur at regular intervals: every second minute or so the drooping lid is raised, the globe wanders toward midline, the pupil contracts, and accommodation increases (Figure 23-6,B). The spasms last from about 10 to 30 seconds and then give way again to the paretic phase. These cyclic movements persist unchanged for many years; as far as is known they continue throughout the patient's lifetime. They go on even during sleep, though at a reduced rate and amplitude; and they subside only in deep narcosis. In many patients attempted adduction of the globe and vertical gaze or accommodative efforts favor the spastic phase and abduction of the eye favors the paretic phase of the ocular cycles. Since this phenomenon was first described, opinions have been divided about its mechanism and about the location of the responsible defect. There were two main trends of thought: one placed the lesion into the oculomotor nucleus, and the other postulated a basal third nerve defect. These two kinds of damage are, however, not mutually exclusive. To the contrary, an injury to the efferent third nerve fibers must bring about retrograde degeneration of the corresponding oculomotor neurons, so that the lesion affects not only the efferent third nerve or the nucleus, but involves them both: the third nerve fibers primarily by the disease process, and the nucleus secondarily by retrograde degeneration. In addition, such retrograde nuclear damage early in life is likely to interfere with the establishment of proper synaptic contacts between the oculomotor neurons and their still immature supranuclear connections; and this may explain the mechanism of the intermittent spasms. 23. Special Oculomotor Syndromes / 1057 B. Historical Background In 1884 Rampoldi described a fascinating case of "oculo-palpebral imbalance." A 4-year-old girl, beautiful and without signs of disease, had begun, at the age of 10 months, to move her eyelids in a most unusual way: they went up and down, alternately on the right and on the left side. The lid would hang flaccid at one time, but soon a number of fast, tremor-like jerks would appear. These would increase, and then the lid would go up and remain spastically retracted for about a minute, in order to droop down again while the other lid lifted. The rhythmic spasms were more marked on the right than on the left side; and while the involuntary movements were extensive, voluntary lifting of the lids was much reduced. But this was not all: other eye muscles participated in the intermittent spasms. When the lid was flaccid, the eye was deviated outward and all voluntary movements except abduction were poor; at the same time the pupil was large and reacted only inextensively to light. And while the lid lifted the globe rolled toward midline, the pupil became miotic, and the accommodative near point moved closer. These rhythmic alternations of spasm and paresis of the muscles innervated by the third nerve had been going on continuously since they were first observed, with little variation. The right eye even continued to cycle while the child slept, but the left eye remained closed. During wakefulness the cycles were faster than during sleep, and attempts at near fixation seemed to favor the spastic phase. Two years later Rampoldi saw a second case quite similar to the first one, except that only the left eye was affected. From that time to 1975, fifty-five additional A. SPASTIC PHASE B. PARETIC PHASE cases were described as having this syndrome. We have summarized the pertinent details of these cases in Table 23-4 ( clinical data on the left-hand pages, ocular findings on the right). However, three patients (numbers 4, 6, and 49) did not fit within this group. In these, the oculomotor pathology began much later in life than in the rest, and both the pupillary phenomenon and the course of the condition were unusual. (1) Bechterew's patient (number 4) was a 24-year-old syphilitic woman with numerous pathologic signs, including right-sided temporal periostosis, sensory and motor changes, and petit mal seizures. Her pupil was unresponsive to all stimuli. Accommodation and the lid were paralyzed, and the globe was fixed in the primary position, with loss of all voluntary movements. The pupil, globe, and accommodation never cycled, nor did the lid move until she began to improve under antisyphilitic treatment. The lid then began to show short spasms: it was raised quickly and remained open for some seconds, at first about once a week and then more often. About 1 to 2 months after these movements had begun they became quite fast and relatively regular. Every 2 to 3 minutes the lid would open and would remain open for from half a minute to a minute. Later these cycles lessened, and within another 2 months they had subsided. There was a partial ptosis and the horizontal eye movements had improved. (2) Lindenmeyer's case (number 7) also had relatively few spastic episodes, limited to the lid: she had a complete third nerve palsy, and several times per day the lid would lift for a short time. (3) Steven's patient (number 49), a 23-year-old woman with an expanding midbrain lesion, had no intermittent spasms at all. Her extraocular movements, lid, and pupil were normal except during short paralytic attacks during which she could not adduct her eye, her lid drooped, and her pupil was large and fixed to all stimuli. Such attacks could be triggered by strong abduction of the globe, and they lasted from 30 to 60 seconds. Eighteen months later these attacks had ceased, but the patient's neurologic condition had worsened. We omitted these three cases from consideration when we analyzed this syndrome during 1973-1975, leaving fifty-four typical cases. For deta~ls b~yond the following summary, the original pubhcat10n should be consulted (Loewenfeld and Thompson, 1975). Figure 23-6. Oculomotor paresis with cyclic spasms (case 48 of Table 23-4). The lower picture was taken in the paretic phase. Behind the ptotic lid the eye was deviated outward and the pupil was large. The upper picture shows the brief spastic phase. The lid lifted, the eye moved toward midline, and the pupil constricted. (From I.E. Loewenfeld and H.S. Thompson, Survey Ophthal .. 20 [1975]: 81) 1058 Table 23-4. YEAR # 1 IV. Pupillary Pathology: Symptomalogy Cases with cyclic oculomotor spasm and paresis described in the literature: Clinical data and ocular findings A Tl!OR 4 Rampoldi 1 18 6 Rarnpoldi 2 1 91 Salzmann 1 93 & Fuchs 1 95 3 1900 4 Bechtc,·ew 1901 Axenfeld 5 &Schilren berg 1903 Bielschowsky 6 SEX EYE AGE* ~ o.u. 10m (4.5y) healthy family, child; no birth healthy trauma V: normal F: normal poor light reflex; could not measure accommodation ptosis 0. CT., less marked on left side eyes turned out, L more than R; all movements except abduction poor on R and absent on L side o.s. ct' cong. (7y) healthy fam Uy, healthy child; no birth trauma V: normal F: normal pupils n.s.; accommodation normal semi-ptosis; no voluntary control eyes turned out; adduction reduced; up-gaze slight; down-gaze almost normal; abduction normal ~ o.s. 2y ( 2ly) mother died of epilepsy; onset of oculornotor defect after sore throat, probably diphtheria V: n.s. F: n.s. pupil fixed to light; accommodation n.s. marked ptosis; no volw1tary control eyes turned out and sl. up; adduction &up-gaze absent; down-gaze very poor; 6th and 4th nerves intact O.D. ~ 24y (24y) recent headaches & bouts of unconsciousness; temporal periostitis; r, hcmiparesis; r.paresis Nn4,5,6,7,8 V: fogged at near F: n.s. pupil fixed to all stimuli; accommodation paralyzed full ptosis; eyes straight ahead, globe slight volW1tar_y fixed; later regained horicontrol zontal but not vertical eye movements (Hg treatments) ~ o.s. cong. (6.5y) normal parents, healthy child; non-traumatic birth; had otitis media V: good; F: normal pupil fixed to light and near; accommodation paralyzed paralytic ptosis; no voluntary control eyes deviated out; adduction, up- and down-gaze paralyzed; abduction normal ~ 4w (20y) normal birth; at age 4w lid droop &bilateral nystagmus, horizontal on left & rotatory on right side V: 5/l00onright, normal on left side; F: normal 0. U. pupil fixed to light and near; accommodation normal full ptosis; no voluntary control eyes turned out and slightly down; adduction & down-gaze poor, up-gaze lost; abduction and 4th nerve intact ~ 17 .5_y (19y) unknown condition, starting in optic chiasm - gradual left hemianopsia -stationary for 5 _years V: R almost n.s. full ptosis no volW1tary control external squint; eye movements O.D. IIISTORY, SIG1 S NEUROLOGIC Fundi Vision, PHASE Eye Position in primary gaze, and voluntary movements no volW1tary 1904 7 Lindenmeyer O.D. 1906 8 Aurand & Breuil O.D. ~ lm (Sy) parents and one sibling had Tbc., 1 sibling died in convuls ion; non-traumatic birth; Hutchinson teeth pupil fixed to all V: R 1/3, L 1/2, stimuli; h_ypermetropic astigmatism O. U. accomodation imperfect F: normal incomplete ptosis divergent strabism; very little adduction, no up- or down-gaze; good abduction 1906 9 Fromaget !;> o.s. cong. (38y) non-traumatic birth, no illness; no change in eye signs since birth V: R normal L amblyopic; F: normal no pupil reflexes described; accommodation n.s. incomplete ptosis marked divergent squint; no adduction, no up- or down-gaze 1907 10 Levinsohn ~ 3m (6y) healthy family, healthy child; oculomotor defect may have been congenital V: R 1/5 L normal; F: normal pupil fixed to all stimuli; accomodation: 4D hypermetrope almost ptosis full O.D. divergent squint; slight adduction and down -gaze; no up-gaze; good abduction 1909 Franke #1 healili_y child; defect V: normal F: normal pupil fixed to all stimuli; could not measure accomodation ptos is o¥u. ly (3y) slight 11 divergent squint; adduction, up- and down-gaze paralyzed 1909 12 Franke #2 ~ cong. ( 16y) mother saw squint at birth; child seen age 6 m: no cycles then noted - may have been overlooked V: 1/20, myopic 6D; F: normal pupil fixed to light; accomodation reduced slight ptos is O.D. divergent squint; adduction, up- and down-gaze paralyzed 1910 13 Paterson ~ early infancy (4y) V: normal F: normal pupil reacted to light; emmetrope in flaccid phase partial ptosis; could lift lid to almost normal eye deviated out; adduction and down-gaze "quite normal"; up-gaze very poor 1912 14 Hesse V: R 0.2,myopic pupil fixed to all stimuli; accommodation: un clear statement full ptosis marked external squint; adduction, up - and down -gaze abolished; 4th and 6th nerves intact 1912 15 Salus pupil contracted slightly to light; accommodation paretic almost complete ptosis divergent squint; 1 mm adduction, no up- or downgaze; full abduction 1912 16 Krfuner #1 pupil fixed to all stimuli; accomodation ? (amblyopic) full ptosis external squint; no voluntary movements involving 3rd nerve; had had surgery for ptosis and squint O.D. o¥u. ~ O.D. ct' O.D. healthy child family, no other healthy given; came for surgery blind; L hemianopic CONDITIOK IN PARETIC Pupil, AccomoLid dation cong. (20y) no history cosmetic 5y (20y) said onset at time of surgery (or neck glands; had facial asymmetry R( L, and large, tortuous veins R lid L normal F: normal 5y ( 2ly) parents thought onset related to surgery for neck glands V: R amblyopic, L normal; F: n.s. #=case numbers assigned for this publication; *=age seen by author·; V: best corrected acuity; correction arc given - these arc not always complete. astigmatism; L normal; F: normal V: R 0.1 without brackets not given unless denotes stressed age at onset of oculomotor defect; age with brackets = age when by author; n.s. = not reported by author;all data supplied by authors 23. Special Oculomotor Syndromes # CHANGES Extent of Cycles 1 I SPASTIC PHASE 1059 / EFFECT OF ATTEMPTED EYE MOVEMENTS OTHER FINDINGS near fixation phase R cycled in sleep, L not; cycles were slower asleep than awake; eserinc, atropine used pilocarpine, Timing of Cycles * G: L: P: A: adduction in spasms, R>L Cycled, R>L mydriasis -- m ios is, R> L near point moved in eyes alternated, 1/2 - 2 minutes cycle 2 G: L: P: A: rolled in in spastic phase ptosis --almost normal enlarged -- contracted no cycles mentioned short-lasting spastic phases ( no details given) 3 G: L: P: A: rolled in to midline p.f. 3 mmalmost 6- mm-3 mm n.s. contraction fast -miosis seconds -dilation slower; cycles about two per minute G: L: P: A: did not cycle flaccidspastic did not cycle n.s. per favored spastic attempted eye movements not block spasms did cycles continued eserine-miosis in deep sleep and in adduction enhanced spasms, abduction reduced extent and up- or down-effort frequency; had no influence on attempted adduction the lid went up, and on abduction down, in either phase lid was raised quickly - spastic for seconds; lid drooped slowly; several cycles/hour voluntary eye movements not influence cycles lid cycled in sleep, but less than when awake; cycles became less frequent when patient recovered from neurologic deficits G: rolled in to midline L: full ptosis --normal P :>normal normal A: increased 6D in spasms cycles slightly irregular; spastic 5-15 secs gradual relaxation; 1-3 minutes per cycle n.s. cycles tired; sleep; 6 G: L: P: A: rolled in 7 mm full ptosis - did not cycle 9mm~3 mm + 2 .5 D - 5 .5 D contraction about 5 seconds, dilation 10 seconds; cycles were ir20-30 sec/phase regular, adduction elicited and maintained abduction prevented or spasms, aborted them emotional excitement prolonged spasms and aborted flaccid phase; no cycles except in primary gaze (cycles were frozen on lateral gaze) 7 G: L: P: A: n.s. ptos is - spastic retraction no cycles seen could not measure lid 1ifted quickly for short time, several times a day - more when tired n.s. cycles seen in sleep- relatively few spasms occurred fairly episodes; regularly during the next 5 years 8 G: L: P: A: no cycles described no cycles described 6 mm-lmm no cycles described each movement about 15 seconds; cycles were slow and irregular light or convergence-accommoelation-efforts had no influence on cycles body position (prone or standing), emotions, accelerated respiration or pulse (running) had no iniluence on cycles used eserine, atropine 9 G: L: P: A: no cycles described no cycles described maxima1-2 mm n.s. contracted in 8-10 seconds spastic 10 seconds -dilated in 30 seconds maximal for 3-4 seconds no effect mentioned no further 10 G: L: P: A: did not cycle did not cycle 9 mm-2.5-3 -4D---1D contracted in 1-5 seconds, dilated in 10 seconds; each phase lasted about 20-30 seconds adduction induced and lengthened miosis and reduced mydriasis; abduction blocked miosis; lid-close increased miosis convergence also increased extent and duration of miosis; cycles continued during sleep 11 G: L: P: A: no cycles described did not cycle 5-6 mm-1.5 - 2 mm could not measure it dilated in 5-20 seconds, contracted faster; each phase lasted 10-20 seconds convergence increased and accelerated spasms; lid-close, up- or down-efforts had no influence cycles increased when the child was upset or felt badly 12 G: L: P: A: did not cycle did not cycle less extensive than # 11 increased during spasms timing # 11 miosis was maintained on attempted adduction and while reading no further 13 G: L: P: A: no cycles described cycled slightly 5 mm--2.5 mm emmetrope -marked miosis maintained 1-2 seconds, dilation much longer; cycles lasted 3040 seconds, irregularly cycles gence, 3rd nerve involvement was much less marked than in most cases 14 G: rolled in slightly L: ptosis-almost normal P: 7 mm - 2 - 2 .5 mm A:+ 5D+ 7D (horizontal) constricted in 10-15 secs - spastic about 10 secs - relaxed in 20-25 secs -naccid for 25-30 secs attempted near vision hastened miosis; adduction and abduction had no noticeable effect no further 15 G: no cycles described L: ptosis -almost normal P: 8 mm-3 mm A:+ 1D-+ 3D miosis 10 30 seconds slow, irregular dilation; cycles lasted 1 min. 10 secs to 2 1/4 minutes convergence, up-, down- or adduction-efforts speeded cycles, favoring spasms; abduction had no influence 16 G: L: P: A: contraction about 2 secs dilated in 4 secs; each phase lasted about 25 35 seconds bright light, near-effort and 1idclose shortened and retarded mydriasis; adduction and abduction had no influence cycles were speeded by emotions, slowed in sleep; no nystagmus when rotating patient to left but + to right; rotation & cooling of labyrinth had no effect on cycles; used cocaine, adrenaline, eserine, atropine --4 5 normal < mm no cycles described cycled 8.5 mm-3 mm did not cycle # - case numbers accommodation; myop. slower - did became slower when patient was 2-5 minutes per cycle during cocaine atropine, used eserine, details than in were affected by conver accommodation, and light (same as m Figure lA), *·• G ~ovements_ of globe durmg p. f. = palpebral fissure; n. s. - 1nformat1on not given. cycles; L= lid-movements; details details used adrenaline, and atropine given pilocarpine, P= pupil movements; eserine A= changes in 1060 / IV. Pupillary Pathology: Symptomalogy Table 23-4 (continued) YEAR AUTHOR SEX EYE AGE* ~ cong. ( 15y) healthy family; parents noted phenomenon at birth V: n.s. R, normal L; F: n.s. pupil fixed to light and near; accommodation n.s. semi -p tos is (palpebral fissure 7 mm) 23° external squint; all movements mediated by 3rd nerve paretic ,;> no history n.s. pupil fixed to light; accommodation n.s. paralytic third nerve paralysis details ·given) healthy family; phenomenon seen after measles ( no squint before): eye did not close fully in sleep V: R 6/6 L 6/24 with + 2D; F: n.s. pupil fixed to all stimuli; accommc dation impaired ( not clear) partial 3m ( 19y) had been well otherwise; surgery for ptosis 10-lly earlier V: 5/9 with - 1.25 D; F: n.s. slight light refiex at start of dilation; accommodation impaired no voluntary control (surgery for ptosis) adduction and dmvn-gaze much restricted; almost no up-gaze; convergence normal in spastic phase O.D. 6m (6y) healthy family, non- traumatic birth; sl.paresis R 5th & L 7th & 9th nerves; no Bell's ph. L; poor vestib. nystagm. V: R emmetrope in flaccid phase; L 1.0; F: n.s. pupil fixed to light and near; accommodation n.s. incomplete ptosis divergent squint; adducution 2mm; qo up- or down-gaze; abduction and 4th nerve normal 1913 Masso 22 ~ o.s. lsty (5.5y) healthy family, healthy child; non-traumatic birth; asymmetric face V: n.s. F: normal pupil fixed to light and near; accommodation n.s. ptosis adduction, up-and downgaze abolished; 6th and 4th nerves normal 1913 23 Uhthoff ~ o.s. ly (9y) healthy family, healthy child; eye phenomenon first noted at age 1 without previous disease V: R normal, L 1/2, hype rm. astigmatism; F: normal slight flexes phase; dation incomplete ptosis 3rd nerve paralysis; 6th nerves normal 1913 24 Zamorani early childhood ( 18y) no significant history; always had 3rd nerve palsy; slight facial asymmetry, R<L V: R amblyopic, L normal; F: normal pupil fixed to light; accommodation n.s. (amblyopia) paralytic ptosis almost no adduction; no upor down-gaze; 4th nerve impaired, 6th nerve intact * 1912 Kramer 17 #-2 O.D. 1912 18 n.s. cong. ( 12y) 1913 Greeves 19 ~ o.s. ( y) 1913 20 Herbert n.s. 1913 21 Lauber Meissner ~ ~ ~ O.D. 7y IIISTOHY, SIGNS NEUROLOGIC Vision, given Fundi r'l>NDITJi>M IN PA RE TIC PHASE Pupil, Accomo Lid Eye Position in primary gaze, dation and voluntary movements light rein flaccid accommoparetic ptos is ptosis (no adduction up to m idline; upand down-gaze abolished; abduction good; could converge during spasms 4th and divergent squint; adduction and down-gaze reduced 1/2; no up-gaze; abduction normal 1914 Coats 25 ~ o.s. cong. ( l0y) at birth had swollen lids left; this lasted 5-6 w -+ eye cycles noted; healthy, but had facial asymmetry R> L V:Rf.c. at 1 ft, asi.gmatic, L normal; F: normal reacted to light in flaccid phase; accommodation n.s. (amblyopia) partial 1914 Groet26 huysen O.D. ~ cong. ( 18y) healthy family, never sick except measles; no neurologic signs V: 0.2, hypermetropic astgmatism; F: normal pupil fixed to all stimuli; accommodation n.s. (amblyopia) palpebral fissure 5mm divergent squint; adduction slightly past midline; no upor down-gaze; abduction normal 1914 v. Hippe! 27 ~ o.s. cong. ( 18y) no significant phenomenon V: R 20/20, L 5/7, hypermetropic astig. F: normal pupil fixed to all stimuli; accommodation paretic marked incomplete ptosis divergent squint; adduction past midline, no up- or down-gaze; abduction normal 1924 Kubik 28 ~ 6m (22y) congenital 3rd nerve palsy, but no cycles age 11 (seen twice ) ; facial asymmetry R<L; weak, asymm. DTR's n.s. O.D. inextensive light slight ptos is reflexes, more in (surgery) flaccid phase; !OD accommodation slightly exo (surgery): adduction just pastmidline; no up- ordown-gaze;no Bell's phen. ; 4th & 6th nerves intact 1927 29 ~ 6m (6y) convulsions at age Gmptosis & external squint; Wa. weakly +; Hutchinson teeth; no other signs V: R amblyopic, L n.s.; F: normal pupil fixed to light; accommodation normal semi-ptosis O.D. divergent squint; adduction, up- and down-gaze limited O" cong. (lly) at age 2 chorea which improved, but still had chore- V: R amblyopic, L normal; F: normal pupil fixed to light and near; accommodation ooor {an1blvooia) pupil active except when in full miosisormydriasis; accom. present full ptosis; voluntary control slight reflexes to light&near, variable with cycle; accom. decreasec ptosis Veil 1928 Frigerio 30 O.D. history; noted at birth atic movements 1928 31 Bielschowsh.-y #-1 1928 Bielschowsky 32 #2 O.D. ly ( 13y) ~ o.s. (ly ( 14y) ~ in arms, trunk and shoulders 3rd nerve palsy age 1 , but nocyclesatage 6-7; neurologically normal; some rotatory movements O.S. V: R 2/4, L 4/4; F: normal ptosis developed during 1st year of life; healthy otherwise; held head crooked V: R 6/6, L 6/8; F: normal ptosis no • lid paretic (had had 2 operations for ptosis) #-= case numbers assigned for this publication; * = without brackets denotes age al onset of oculomotor seen by author; V = best corrected acuity; n.s. = not reported by author; all data supplied by authors slight divergent squint; all 3rd and 4th nerve movements abolished; 6th nerve parelic eye slightly down & out (two operations); adduction, upand down-gaze paralyzed; abduction partial; 4th n. intact eye slightly down & out; adduction poor, up-gaze absent; down-gaze slightly limited; abduction good defect; age with brackets= age when arc given - these are not always complete. 23. Special Oculomotor CHANGES I Extent 17 of Cycles IN SPASTIC PHASE Timing * of Cycles Syndromes EFFECT OF ATTEMPTED EYE MOVEME, TS OTII ER FINDINGS between cycles 1061 and G: rolled in from 23° -19°exo L: p.f. 7mm -.J2mm ( > n) P: 7mm -3mm A: n.s. G: rolled in during spasms L: lifted during spasms P:8mm-3mm A: n.s. m iotic phase 12 -3 0 seconds; mydriatic phase 65-120 seconds attempted adduction delayed or interrupted myd rias is; lidclosc had no influence found blood no details n.s. n. s. 19 G: L: P: A: rolled in to midline moved up during spasms contracted fully in spasms increased + 3 .5D in spasms but timing varied, spastic and paretic phases remained equal (for example 20 sec .-.20 sec.) light or attempted accommoelation did not affect cycles did atropine, 20 G: L: P: A: no rotation cycled 6mm - l.5mm increased + 3D in spasms spastic phases about 15 flaccid about seconds, 25 seconds; timing nearly constant convergence, adduction and elevation efforts lengthened spasm and reduced amplitude of mydriasis; abduction the reverse cycles continued in sleep, and flaccid phases nearly 21 G: L: P: A: rolled in just past midline ..- 9-l0mm p.f. 5-6mm 7.5mm -1.5 - 2mm emmetrope - + 6D contracted in 1.5-4 secs. -mibsis 15-40 secs.dilated in 10-20 secs pause 30-90 seconds adduction lengthened spasms, abduction shortened them; light and accommodation had no influence on cycles cycles were faster awake than asleep; mydriasis was only 4mm in sleep; on L had slight lagophthalmos in sleep; cocaine tests pilocarpine, atropine, 22 G: L: P: A: rolled in slightly flaccid ....,completely raised 9mn1 --3 mm increased + 3D in spasms contracted in 6-8 secs miosis 15-30 seconds dilated in 15-30 seconds -pause 12-15 seconds light and forced lid closure retarded mydriasis; convergence and attempted eye movements had no influence on cycles or fast respiration, body posit ion, normal sensory stimuli had no influence on cycles; could not see cycles in sleep; cocaine and atropine tests done 23 G: L: P: A: did not cycle did not cycle 8-9 mm -- 2-3 mm increased + ID in spasms contracted in 2-3 secs miosis 6-8 seconds dilated in 10-15 secs mydriasis 8-12 seconds adduction-, abductionand lidclose efforts had no influence on cycles in deep sleep pupil measured 3 mm and cycles ceased; in narcosis cycles were almost abolished; pilocarpine and atropine tests done 24 G: L: P: A: n.s. ptosis max. n.s. --..retracted)normal mydriasis ---miosis flaccid 25-40 seconds _., spastic phases shorter; tota! cycles 40-60 secs, dilation &contraction 10-15" adduction mydriasis; miosis cycles continued in sleep and were speeded by mental stimuli; no coincidence with pulse or respiration; cocaine, atropine tests done eserine, 25 G: L: P: A: often rolled in during spasms partial ptosis-+slight raising; 6-7mm _,..2.5-3mm ciliary muscle contracted contracted in 5 seconds _., dilation slower ( 1 minute or more); cycles irregular in time and extent adduction or near-efforts tended abduction myto cause miosis, driasis, but cycles continued; upor down-effort had little influence pressure on carotid artery had no effect on cycles; bright light reduced mydrias is 26 G: rolled in during spasms L:p.f. 5mm--normal P: 8mm---4mm A: - 3.5 D _.,+ 3 D contracted - miosis dilated in flaccid 15 adduction and near fixation aborted paralysis, prolonged and increasec miosis; abduction prolonged flaccic phase with flaccid cycles continued in sleep, phase three times longer; raising pulse to 150/minute did not affect cycles; eserine and atropine tests done 27 G: rolled in past midline L: p.f. 5mm-normal P: 5mm-2mm A:-3D--+3D contracted in 5-15 secs miosis 20-50 seconds dilated in 5-15 seconds flaccid shorter than spastic adduction prolonged and increased miosis; abduction prolonged and increased mydriasis; up- or downeffort had no influence on cycles in sleep lid remained closed but twitched; innervation of frontal muscles, chewing, L carotid compression had no influence on eserine, atropine tests cycles; cocaine, 28 G: L: P: A: did not cycle slight ptosis _,.retracted> n 7.5mm -4mm ( <n) no cycles - l0D in eitherph. spastic a few seconds _. adduction, up- or down-efforts relaxed gradually; pa retie increased spasms but did not about 1 minute; average 14 affect timing; abduction had no - 16 cycles per 15 minutes influence on cycles cycles continued in sleep and in veronal narcosis; in any part of cycle lid moved up suddenly and pupil contracted a bit on attempted eye movement; cocaine ,adrenaline 29 G: L: P: A: n.s. n.s. cycled normal mydriatic phase was shorter than m iotic phase "far vision elicited miosis and attempted convergence mydriasis, but this was not constant" (printer's error ?) pilocarpine, cocaine, tests done 30 G: L: P: A: rolled in short of midline full ptosis -+-normal mydriasis --..markedmiosis no cycles described miosis 55-57 seconds, mydriasis 1.5 - 2 minutes; contraction was faster than dilation not discussed lid movements 31 G: L: P: A: no cycles described fullptosis .-almost max. up 8mn1--..2mm increased 8-l0D in spasms miosis 10-20 seconds; dilated in 10-30 seconds; full cycles lasted 1 - 3 minutes convergence and lidadduction, close efforts increased and prolonged miosis; abduction decreased and shortened miosis excitement and eye movements accelerated cycles and reduced mydriasis to 56 mm; cycles persisted in sleep 32 G: L: P: A: no cycles described ptosis -- retraction 7 .5 - 8 n1m __.. 2 .5 mm cycled 2 - 3 mm miotic phase 10 seconds; mydriatic phase much longer adduction, convergence and 1 idclose efforts favored m ios is; abduction favored mydriasis on down-gaze had pseudo-von phenomenon in either phase; persisted in sleep 1 I#= case numbers accommodation; given in 4-5 seconds 20 seconds -7 -8 seconds seconds (no details) (same P • f. as in Table = palpebral and convergence stopped abduction retarded lA); * = movements of globe during cycles, L = lid-movements, fissure; n. s. = information not given; "= seconds. p = pupil no relation pressure / eserine, movements, were cocaine tests with spastic equal atropine eserine, visible in sleep Graefe cycles A= changes in 1062 Table 23-4 IV. Pupillary Pathology: Symptomalogy (continued) YEAR If A THOR 192 1929 33 Bielschows.ky #3 1929 Biel34 schowsky 114 1930 35 Selinger 1930 36 Petrovic & Tschemolossow 1931 Stein 37 SEX EYE O"' o.s. O"' 0.0. O"' AGE* cong. y) HlSTORY, SIG s 'EUROLOGIC Vision, Fundi CONDlTl"N pupil, Accomodation W PA D1"'T'Tf' PHASE Lid Eye Position in primary gaze and voluntary movements in extensive I ight reflexes, varied with cycle; accomm. n.s. pupil fixed to all stimuli; accommodation n.s. fl ace id ptos is with twitches; no voluntary control 2 mm proptosis; no adduction, up- or down-gaze; abduction good flaccid ptos is; no voluntary control 30° divergent & slightly down; adduction, up- and down-gaze abolished; 4th and 6th nerves intact (] healthy family; had always been healthy otherwise V: R 6/6, L 1/12; F: normal cong. ( 14y) no history given; seen only once V: H 6/15, L 6/6; F: n.s. mother insane; child Ju s, 4+ Wa in CSF, son teeth, IQ 71; 3rd cong,butcycles 14y V: R 3/200, L 20/20; F: normal slight light reflexes in fl ace id phase; accommodation n. s. palpebral fissure 3mm eye 40-45° out (several operations); poor adduction, no up- or down-gaze; good abduction; 4th nerve intact --cong. congen. Hutchin• n. palsy later 0.0. ( 16y) ~ 7y ( 17y) "fainted" with convulsions after fright - bilat. involunl lid-liiting-L "cured" by electricity; aunt said to have had this 2y postpartum V: R 0.2 - 0.3, L normal; F: normal no physiologic function describcd sem i-ptos is external squint; adduction, up- and down-gaze limited ly first O.5yof liie had febrile disease with convulsions squint; otherwise healthy V: R 6/2, L 6/6; F: normal minimal reactions to light and lidclose; accomodation paralyzed palpebral fissure 3-4 mm; could liit lid 2 -3 mm 15° divergent squint; almost no ad due tion or down -gaze; up-gaze 2 mm; 6th nerve intact 0.0. O"' O.D. (28y) 1932 Biel3 schowsky #1 o.s. cong. no significant history; eye "young" signs since earliest childhood; 2mm proptosis V: R normal, L 6/24, hyperop. astigmatism; F: n.s. reduced light relid parctic flexes in flaccid phase; could not measure accomm. eye slightly down & out; no adduction, up- or down-gaze abduction good, 4th nerve normal 1932 Biel39 schowsky #2 !;? o.s. cong. ( 19y) ptosis and external squint from birth; onset of cycles unknown V: R 6/5, L 1/60, astigmatic; F: n.s. reduced reactions to light and near; accommodation n.s. external squint; all muscles supplied by 3rd nerve paralyzed O.D. 3w (9y) unknown cause; healthy child; small involuntary l:\vitches of outstretched hands and legs V: R 1/10, L 8/10 ; F: n.s. pup ii fixed to light no voluntary lidopening; pseudoand near; no voluntary von Graefe in spasyic phase accommodation divergent squint; adduction abolished; up- and downgaze very poor; 4th and 6th nerves intact ~ o.s. cong. ( 1 y) admitted witb acute febrile illness ( basal meningitis or abscess - improved; said OS was always"bad"&!'small" V: R normal, L "bad"; F: n.s. pupil fixed to light and near; accommodation abolished palpebral fissure 3mm 200 external squint; adduclion, up- and down-gaze limited !;? cong. (20y) no significant V: Rf.m.at L20/20; F: n.s. pupil fixed to all stimuli; accommodation n.s. (amblyop ia) palpebral fissure 3 mm; could not 1lit lid very marked external squint; paralysis of all muscles supplied by 3rd nerve; 4th and 6th nerves intact ly (Sy) ptos is developed at age 1 n.s. n.s. n.s. n.s. cong. (44y) patient said his mother had the same condition; had nystagmus at lateral gaze to either side V: R 1/40, astigmatic, L 2/3; F: n.s. pupil fixed to light and near; accommodation poor ptosis; no voluntary control. divergent squint; adduction, up - and down -gaze abolished abduction and 4th nerve normal eye slightly exo (surgery); palpebral adduction, up- and downfissure 3-4mm (surgery); no vo gaze limited; abduction poor; 4th nerve intact -luntary control divergent squint; adduction, almost complete up- and down-gaze absent; ptosis; no abduction normal voluntary control 1932 Mak van 40 Waay 1937 Hicks & 41 Hosford #1 1937 42 Hicks & Hosford #2 1939 43 Bielschowsky 1941 44 Bonnet 1942 45 Lowenstein & Givner 1945 46 McGregor O"' 0.0. o-r O.D. O"' O.D. Burian & Van Allen history gradually 3 ft, lid flaccid o.s. a" cong. (32y) twin brother died at birth; ptosis age 6 m - 3 oper. ; cycles seen age 22; weak OTR's; sl.twitches Rarm V: R 20/20, L 10/200,myop. astigmatism; F: normal reduced light reflexes in flaccid phase; accomm. ? (amblyopia) ~ cong. ( Sy) healthy family, healthy child· no birth trauma, but ( congenital) thickening of sphenoid ridge; neurol.normal V: R 6/18, hyperopic astigmat., L 6/9 F: n.s. poor reactions to light and near, lid-close &pain; accommod. "? normal birth and developmcnt; eye signs noted at birth V: R amblyopic (l.p.), L normal F: normal pupil fixed to light; accommodation ? (amblyopic) ptosis normal birth, healthy child, but was large infant -hyper -kinetic child; EEG anomaly; ptosis developed in 1st year V: R 6/30-6/12, L 6/9; F: normal pupil fixed to light and near; accommodation n.s. (amblyopic) complete O.D. 1949 Drucker 47 1963 48 O"' ~ O.D. ~ O.D. cong. (9y) (ly (6y) 50° exotropic; all muscles supplied by 3rd nerve paralyzed; 4th and 6th nerves intact ptosis eye deviated down &out (surgery at 11 m); virtually no adduction or up-gaze, little down-gaze or abduction II = case numbers assigned for this publication; *= without brackets denotes age at onset of oculomotor defect; age with brackets= when seen by author; V= best corrected acuity; n.s.= not reported by author: all data supplied by authors arc given - these arc partly incomplete. 1063 23. Special Oculomotor Syndromes CHANGES ii Extent of Cycles IN SPASTIC OTHER no cycles described flaccid-. retracted 5mm ...-3mm cycled about 1 cycle per minute, more irregular than cases # 31 and 32, due to effect of intended movements adduction and up-gaze effoets elicited spasms; abduction aborted spasms on attempted adduction lid went up quickly 3 mm and accomodation inct· ased, in either phase; lid went down and accommodation decreased on abduction; cycles con tin. in sl p spastic phase was prolonged when patient was excited; cycles continued in sleep of Cycles Fl 'Di GS EFFECT OF ATTEl\lPTED EYE MOVEMENTS PHASE Timing * 33 G: L: P: A: 34 G: no cycles mentioned T.: flaccid ptosis -+- lifted P: mm -+-2.5mm A: increased slightly in spasms spastic about 10 seconds; full cycles about one per minute adduction phase 35 G: L: P: A: 40-45° ext. squint-+ 5-80 p.f. 3mm-. 8-9mm 8mm -.3mm cycled with 3.5D extent contracted rapidly_. miosis 20 seconds -.dilated in 20-25 secs - flaccid20secs;cycles60-80" up- or downlight, adduction-, gaze- and convergence efforts had no influence on cycles pseudo-von Graefe phenomenon in spastic homatropine tests pilocarpine, phases; done 36 G: L: P: A: rolled in to midline ptosis - normal mydriasis -- much< n cycled in 4-5D range spastic phases average 15 seconds, paralytic 40 seconds; variable speed from day to day n.s. cycles continued in sleep; excitement prolonged miosis but subcutaneous adrenaline had no influence on cycles; pilocarpine, eserine, cocaine tests 37 G: L: P: A: did not cycle did not cycle 7-8mm .... 2mm increased 2.5D in spasms miosis 10-20 seconds; slow dilation 1 full cycles 1 - 2 minutes convergence and lidadduction, close efforts prolonged & in creased miosis & reduced mydriasis; abduction had reverse effect lid did not cycle but lifted on attempted in adduction in either phase ; changes respiratory rate had no effect :is G: L: P: A: rolled in to midline paresis --normal 5.5mm --2mm (<n) cycled irregular cycles; exact time n. s. adduction effort prolonged miotic phase; abduction hastened mydriasis and maintained it pupil contracted on adduction, abduction in either phase 39 G: L: P: A: n.s. flaccid -.lifted 7.5 mm _.3.5mm n.s. no details could not see influence of attempted eye movements lid did not always ments 40 G: L: P: A: rolled in to almostmidline flaccid-. retracted> n very large_. miosis - 4D--+ 3D spastic about 10 - 15 seconds, flaccid about 50 seconds; cycles were fairly regular n.s. cycles continued jaw movements, carotid occulsion 41 G: L: P: A: did not cycle did not cycle 6mm ...... 2mm increased 2-3D in spasms complete cycles in 2030 seconds; no further detail given attempted eye movements not influence cycles 42 G: L: P: A: rolled in 4-5° p.f. 3 mm ...... normal very large -- 2 mm - 3D-.+ 0.5D whole cycles lasted 23 .5 minutes; paralytic phase was 3 .5 times as long as spastic phase adduction influence 43 G: L: P: A: n.s. ptosis ..-open full mydriasis n.s. spastic phases lasted 10 -2 0 seconds; no further detail reported adduction triggered and maintained spasms; abduction maintained flaccid phase 44 G: L: P: A: rolled a bit past midline ptosis --run opening large ...... marked miosis cycled 1 D miosis several seconds; full cycles about 20 - 30 seconds, not quite regular adduction increased 45 G: L: P: A: rolled in slightly (surgery) p.f. 3-4mm --retracted Smm--3 mm increased 2 Din spasms contracted in 5 seconds -. miosis 35 seconds-+ dilated in 9 seconds -. flaccid for 15-90 seconds no influence of intended extraocular movements noted cycles continued in sleep; irregular EEG traces, but no coincident eye traces were done (probably no time relation); adrenaline, eserine, cocaine tests done 46 G: L: P: A: rolled in slightly 3mm p.f. --fully open 5 - 6 mm -- full contraction increased 1 Din spasms spastic phases lasted about 30 seconds, flaccid phases 1.5 to 2 minutes voluntary influence cycles continued in sleep; they were faster when patient was excited than when quiet; systemic prostigmine had no effect; cocaine, homatropine, eserine, pilocarpine tests 47 G: L: P: A: no cycles described ptosis -- retracted 8mm--2mm increased 4 D in spasms total cycles lasted 90 to 120 seconds n.s. cycles continued during sleep; pseudoGraefe phenomenon in spastic phases; atropine, pilocarpine tests done 48 G: L: P: A: rolled in to midline ptosis -- normal 7mm-. l.5 mm n.s. spastic phases lasted 20 - 30 seconds, flaccid phases about 35 seconds adduction and near-efforts prolonged spastic phases; abduction prolonged flaccid phases cycles slowed or stopped during sleep and in light or medium deep narcosis; dilantin, phenobarbital and librium had no effect; netther did acceleration of pulse or respiration --max. miosis given about hastened spastic and abduction cycles did not move- in sleep, every 3 minutes; pulse, respiration, had no influence on cycles attempted adduction caused about 2 mm in either phase no further and efforts did not rate of cycles #= case numbers (same as in Table IA);*: G = movements of globe during cycles, accommodation; p.f. = palpebral fissure; n.s. = information not given. pupil on at first had atropine in eyes; cycles were discovered when it wore off; on admission and patient was very ill, semi-stuporous irritable when aroused but neurologically neg did impulses hastened spastic phases accompany dilated L= lid-movements, cycles details continued lid to retract given in sleep P= pupil movements, A= changes in von .. 1064 Table 23-4 YEAR * / (continued) AUTIIOR 1965 49 Slevcns 1968 50 Levy AGE* ~ 23y (2325y) occipital headaches, evidence of expanding brain stem lesion, with hemiparesis &ataxia; cycles later stopped Sm ( 14y) 3rd nerve palsy first interV: R 20/20, m illenlconstant; progr. L. h.m.; optic atrophy began 5y after F: atrophic cycles (marked age 14); IQ 70 disc err o.s. Morizane 1970 52 Crone & llorslen 1972 53 1972 1973 55 SEX EYE 0.0. 1970 51 54 IV. Papillary Pathology: Symptomalogy err 1973 57 EUROLOGIC Vision, CONDITION Pupil, Accommodation Fundi V:20/20O.U.; F: first normal -papillcdcma o.u. IN PARETIC Lid PHASE Eye Position in primary gaze and voluntary movements pupil fixed in attacks, normal otherwise; accom pare tic in attacks ptos is in atLacks, normal otherwise free except in attacks; forced abduction tr iggc red these: dev lated down & out and could not adduct; ip- & down n. s. probably no pupil or accommodal. movement:"complete 3rd n. palsy'' ptos is complete external squint; all muscles supplied by 3rd nerve paralyzed; 4th and 6th nerves intact eye exolropic; adduction poor; no up- or down-gaze; abduction imperfect(had surgery) left 3m (9y) di[[icult d livery, born asphyxic; at age 5 had surgery for plosis and esotropia; border!in EEG, end position nyslagmus V: R 20/15, L 20/50; F: normal weak light reflex in fl ace id phase, none in spastic phase; accommodation n.s. ptosis cong. (8y) forceps b irlh; plos is noted at birth; cyclingce1·lain at age 4 (surgery for squint & plosis); EEG findings at age V: R 5/15, L 5/5; F: n.s. no light reflex; accommodation n.s. complete el Sh ikh & O' Moham 0.0. med cong. ( 1 y) healthy family; trauma n.s. n.s. full ptosis eye turned out & down; adduction up to midline; upand down-gaze anil abduction n.s. Susac & mith 6m (3y) healthy family, healthy child; lid droop noticed at age 6 m ( not before); no birth trauma V: R? L good; F: normal slight light reflex inflaccidphasc; accommodation n.s. lid flaccid eye exolropic; adduction lo almost midline;4th and 6th nerves intact; no up- or down-gaze !;? w1 m (lly) no known trauma; R lid puffy atbirth; mothersawpupils R>Lat w;at m febrile dis. with convulsionptosis; cycling definite at 18 m V: R 6/9, L normal; F: normal about I mm light re11ex in flaccid phase, none in spastic; accomm. impaired palpcbral fissure 3mm; could raise lid to 7 mm 15° exotropia; could adduct 40% of normal; upgaze 10%, down-gaze 20% of normal; 4U1 and 6th nerves intact ~ 18m (7.5y) healthy family, normal birth; at 16 m measles & sl. head trauma ( no concussion): lid droop & squint at 18m; cyclGs at 45 m ( perhaps earlier) V: R 6/24 L normal; F: normal slight light reflex inflaccidphase; no near response; could not measure accommodation palpebral fissure 4 mm; could raise lid slightly 200 exotropic; could adduct about 10%ofnormal; no upgaze; down about 10%; 4th and 6th nerves intact ly (3 7y) L eye puffy at birth ( possible trauma); episode of fever at ly-os closed; small, hypcrkinetic chUd V: R 20/20, L 20/ 25 F: normal fairly good light re -flex in flaccid phase; accomm. impaired scmi-ptosis; can lift lid somewhat eye deviated out about 50; adduction and up-gaze 50% of normal, down-gaze good; 4th and 6th nerves intact & Uemura I weltPrice & Trounce o.s. O' 0.0. if 0.0. 0.0. 11 1973 56 IIISTORY, SIGNS lewettPrice & Trounce #2 Thompson 0.0. O' 0. s. #= case numbers assigned for this publication; by author; V = best corrected acuity; n.s. no known *=age without br-ackets = not reported by author; plosis age 4 eye out & down; no adduction, up- or downgaze; no Bell'sphcnomenon; could abduct denotes age at onset of oculomotor defect; age with brackets = age when seen all data supplied by authors are given - these are not always complete. C. Appearance 1. Clinical History Twenty-four of the patients were male and 30 female and all except Rampoldi's first case were unilateral. Patient 36, whose right eye cycled when she was seen, said her left eye had done so also at an earlier time. In twenty-seven cases the history was entirely negative, and there was no pathology other than the ocular syndrome. But in the remaining half of the cases the ocular syndrome was associated with some other condition. In twelve patients there had been difficulties at birth, or there were signs that made birth trauma appear possible (numbers 15, 24, 25, 28, 45, 46, 48, 51, 52, 55, 56, and 57). In six the onset of the ocular syndrome was related in time to acute febrile diseases (numbers 3, 19, 37, 55, 56, and 57). Furthermore, two patients had congenital syphilis (numbers 29 and 35) and two tubercular infections (numbers 15 and 16); and in two additional ones (numbers 8 and 41) infectious diseases may have played a role. Ten patients had additional neurologic signs (numbers 6, 19, 21, 30, 40, 44, 50, 51, and 55). Oculomotor paresis with cyclic spasms thus is often associated with other pathologic conditions, and the assumption of birth trauma or other early damage does not appear as remote as has been thought by some authors. The family history was entirely negative in all but two cases: patient number 44 said that his mother had had 23. Special Oculomotor Syndromes CHANGES If- Extent of Cycles 4H G: L: P: A: IN SPASTIC * DI GS OTHER could induce attack by strong abduction for about 20 seconds: divergent this brought on ptosis, squint and accommodative palsy developed evidence for expanding brain EEG, brain scan and stem lesion: X-ray, probably glioma; pneumo-encephalogram: note that this case differs from cyclic cas contracted in 5 seconds - miotic 10 seconds -dilated in 15 - 20 seconds - mydriatic 15 seconds n.s. brain scan: suspected area of increased uptake L posterior fossa; EEG showed paroxysmal sharp wave activity, arising in L frontal area and cycles continued in sleep, more slowly, increased under physical or emotional stress; borderline EEG with normal sleep pattern; anesthesia, systemic adrenalin, pilocarpine, caffeine, reserpine,tranquilizers cycles; duringsleep, fing r-and mouth-movements in spasms awakened child Timing no cycling, or very slight did not cycle 7mm -2.5mm increased 4 D in spasms 1065 EFFECT OF ATTEMPTED EYE MOVEMENTS PHASE of Cycles attacks lasted 30 secs to 1 minute, with irregular normal intervals could not adduct in attacks ptosis during attacks dilated during attacks paretic during attacks / FI s 50 G: L: P: A: 51 G: 25° exo..,. 10° eso (surgery) L: ptosis-+normal P: 6mm .... 2mm A:+2D-+-+9D contracted in 3 seconds .._ miotic 9-10 seconds -dilated in 8-9 seconds large 6 -7 seconds; total cycles lasted 24 31 seconds cycles persisted wing movements; in spastic phase 52 G: L: P: A: did not cycle ptosis--. wide open mydriasis .._miosis n.s. spastic phases lasted about 20- 30 seconds; full cycles lasted about 2 minutes n.s. cycles continued in sleep; EEG showed paroxysmal activity in R temporal lobe during spastic phases; these occurred shortly after lid movements; some cycles without EEG change 53 G: L: P: A: rolled in to midline full ptosis .._75% up mydriasis -.normal size could not see cycles spastic phases lasted 20 seconds; flaccid phases also 20 seconds adduction provoked spastic phase; abduction provoked paralytic phase no further 54 G: L: P: A: rolled in to m idline flaccid -- retracted 5-6mm-1.5 mm n.s. spastic 10 - 30 seconds, flaccid 30 seconds to 3 minutes; cycles were i1·regular no effect of eye movements; could abduct in spastic phase without altering cycles cycles continued (irregularly) during sleep and were not speeded by stress; anesthesia stopped cycles; had no time-related EEG activity; carotid &vertebral arteriograms norm. 55 G: L: P: A: eye rolled in to midline 3mm5mm p.f. 8mm-3mm cycled about 2-3 D contracted in 3-4 seconds -spastic 41- 1 seconds -dilated in -9 seconds -naccid 4-30 seconds ( average 15 ) attempted adduction elicited and maintained spasms (very marked effect); abduction favored paralysis cycles slowed in light sleep; in deep sleep but lid did not; pupil continued to cycle, EEG was normal: no periodic activity; effort to look straight ahead elicited spasm; this caused relatively long spastic phases 56 G: no movement L:p.f. 4mm-+-10mm(<n) P: 9mm-3.5mm (<n) A: increased during spasms contracted in 3-4 seconds -spastic 9-21 seconds ( average 14) - dilated in 7-8 seconds-+ paretic 25 -54 seconds ( average 41 ) no certain influence of extraocular innervation on extent or timing of cycles mother said O.D. stayed open in sleep; ptosis more marked when child is tired; no pseudo-von Graefe in spasms; normal EEG -no periodic activity; normal air enccphalogram; tens ilon improved ptos is 3-4 minutes 57 G: L: P: A: contracted --..spastic -- dilated paretic for adduction triggers spastic phase; near effort also causes spasm; influence of up-and down gaze & of abduction uncertain ptosis worse when tired; pseudo-von Graefe phenomenon in spastic phase; cycles continued in sleep; tranquilizer did not affect cycles no movement 70% ptosis --. retracted) 5 mm -+ 2 mm ( <n ) cycled about 2 .5 D #= case numbers accommodation; n in 3-4 seconds 10-1:, seconds in 5 seconds -+ 60-120 seconds (as in Table IA);*: G= movements of globe during cycles, p.f. = palpebral fissure; n.s. = information not given. during foliocould converge L= lid movements, P= pupil details movements, A= changes in NOTE: ~nee it wa~ published in 1980, I have not amended this Table because additional cases did not alter the conclusions derived from it, except for some pomts mentioned at the end ofth1s chapter. For additional cases, see Ballet, 1896; Remky, 1954; Walker and Hudson, 1962; Walsh and Hoyt, 1969 Hyams'. Sharf & Newman, 1973; Andersson, 1974; Arseni & al., 1974; Carroll, 1975; Clark & Scott, 1975; Janzen, 1975; MUiler-Jensen, 1975 Br_zeck1&Ruskowska, 1976; Tuszewska&Teppa--Szumowska, 1976; Victor, 1976; DeRenzi&Nichelli, 1977; Miller, 1977; Fells&Collin, 1979 Vo1culescu & al., 1978; Yapp & Sutton, 1982; Zhang & Lu, 1984; Kommerell & al., 1985; 1988. "the same condition," and patient number 36 said that her maternal aunt had had a 2-year period of ocular cycles. Neither person was seen professionally. 2. Onset Typically, the oculomotor palsy (or paresis) was present at birth or developed in infancy, and onset after the age of 2 was rare (Figure 23-7). Of the four patients with later onset, number 19 developed the condition after measles. Numbers 15 and 16 both were said to have shown the defect at the age of 5, after surgery for scrofulous neck glands. This appears odd, and we wonder whether the ocular pathology might have been overlooked earlier, or the precise time of onset forgotten and then related to the memorable event of surgery. In this connection jt appears significant that in both these patients the affected eye was amblyopic, and number 15 had facial asymmetry, with the half-face on the side of the bad eye the smaller one. For number 36 a bizarre history was given that raises some doubts as to the accuracy of the report. This 17-year-old girl reported that at the age of 7 she had been attacked by an angry employer with a knife. She became so frightened that she fainted with convulsions. Next day she fainted again (with convulsions), and 2 days later a third time. Since then she had not lost consciousness again but noted the ocular syndrome. Sometimes one and 1066 / lV. Pupillary Pathology: Symptomalogy then the other eye would open and close rhythmically and involuntarily. Several years later she was treated with electricity and the left eye was "healed" while the right eye continued to cycle. Both the girl and her mother were very nervous, and they said that the mother's sister had had the same kind of attack with convulsions during childbirth, and that the same ocular syndrome had developed in her and was cured 2 years later. U ually the spastic movements were reported (or as urned) to have been present from the start of the oculomotor defect. But in a few cases (numbers 28 31 35, and 45) the spasms were noticed only after pa;esi~ had exi ted for some time. It appears almost the rule that the unusual, cyclic nature of the condition is not recognized immediately. When asked, most patients said that the eye had been this way "for a long time" or "alway ," but they (and often their ophthalmologists) had not paid much attention. Sometimes the condition wa referred to a "oculomotor palsy" (number 39), or wa entirely dismi sect (number 57). Morizane and Uemura's case (number 51) shows that patients' or relatives' statements cannot always be considered conclusive. The parents had noted that their baby's lid "drooped occasionally" when it was 3 months old. Photographs taken at the time showed, however, that the lid sometimes was raised higher than the normal one while the eye pointed inward; at other times it was closed, and in some pictures it was half open and the eye pointed outward. The cyclic pattern was thus established early, but the patient and hi parents were not aware of it until they #52 #49 #45 #44 #40 #37 #33 #32 #31 #27 #26 #25 #24 #17 #16 #13 #11 #8 #7 #5 #2 #51-3mo #50-5mo #42- inf #38-ech #36-ech '#23-ech #19-3mo #9- 3mo #6- 4we #46-lOy #43-6m #35-loy #30-1°y #28-6m #21-loy #20-6m #1-l0m from birth up to 6 months 6months -1 year were told about it by the authors when the child was 9 years old. More patients may exist with "congenital oculomotor palsy" who, in fact, have the cyclic syndrome. One of these was described by Dahme in 1925-1926; and it is interesting that Behr, who saw the patient in 1925, and who had a special interest in the pupil and had discussed the cyclic syndrome at length a year earlier, also failed to recognize it. The patient was a 23-year-old woman with "congenital left-sided oculomotor palsy." Her right eye was normal, but on the left there was ptosis with "occasional spontaneous fibrillary up and down movements." Adduction and vertical eye movements were much reduced, with slight ptosis. Abduction also was limited, probably due to several previous squint operations. The pupil kept changing size without external stimulation: sometimes it was much larger and sometimes much smaller than in the normal eye. The light reflex could be elicited in either phase, but sometimes it was absent. When the patient tried to adduct the eye ( and sometimes also on intended up or down movements) the pupil contracted; and on abduction it dilated slowly to near-maximal size. But sometimes the opposite seemed to happen: the pupil would contract although the eye was abducted, or it would become larger althoug the eye moved in. In this patient the movements probably were cyclic, but since this was not recognized, they appeared confusingly different from time to time. Figure 23-7. Age of onset of oculomotor defect among 54 cases. The numbers are case numbers in Table 23-4. (From I.E. Loewenfeld and H.S. Thompson, Survey Ophthal., 20 [1975]:81) AGE OF PATIENTS AT ONSET #41 #29 #22 #10 1 years #3 #15 #14 #34 #18 #4 2 5 7 later ~ OF OCULOMOTOR DEFECT #39 not clear 23. Special Oculomotor Syndromes 1067 4. Spastic Movements It is intere ting that after publication of our paper on this syndrome in 1975, a number of new cases were quickly found in variou in titutions ( ee below). I have not included the e new ca e in our table because no new details were found that would influence our earlier conclusion about thi yndrome. The paretic muscles did not all participate in the cyclic movements to the sam~ degree (Tables 23-4 and 23-6 and Figure 23-8). Pup1llary cycles were always found, and they were by far the most ex~ensive <:>fall cyclic movements. In many patients their amphtu~e exceeded the range of normal pupillary reflexes. Lid cycles also were marked; and often there was abn?rmally strong innervation of the levator muscle dunng the spastic phases: when the pa~ient ~ooke? straight ~head the lid in the bad eye would hft a little higher than m the normal eye, and when the patient tried to look down the lid would remain contracted, as in the pseudo-van Graefe phenomenon. In twenty-nine patients the globe rolled in during the spastic phases and drifted back out during the paretic intervals. These adductions were, however, not very extensive: the eye never moved further than slightly beyond mid line. Cyclic up and down rotations of the globe were never seen. The timing of the cycles varied among individuals, with extreme values between 20 seconds and 3.5 minutes per cycle (Figure 23-10). The flaccid phases were almost always longer than the spastic phases, and fast cycling favored the spasms: in patients with slow cycles the paretic intervals were up to twelve times longer than the spasms, while in patients with fast cycles the paretic phases were much shorter and the spastic phases about the same. In fast cycles a greater portion of the time was therefore taken up by the spasms. Each patient appeared to have an individual time range, and averages of repeated observations on different days remained fairly constant if the experimental conditions and the patient's physiologic state were the same. But usually the individual cycles varied quite a bit: short cycles and long ones could appear in irregular succession, and short or long flaccid phases followed without apparent pattern after short or after long spastic phases (Figure 23-11). In some patients these spastic movements were smooth, as shown in Figure 23-12,A, but more often they were uneven: the paralyzed lid would show a number of 3. Sensory and Motor Impairment The fundi were normal in all ca e described except in number 50, who began to have progressive optic atrophy 5 year after the cyclic movements had become established. Visual acuity was described as subnormal in forty reports, ranging from only light reduction to profound amblyopia; 6 patients were said to have had "normal" or "good" vision, and eight times vision was not mentioned. There were considerable variations in the degree of oculomotor impairment among patients. Some had total paralysis of all muscles innervated by the third nerve. In others the physiologic movements were preserved to different degrees (see Tables 23-4 and 23-5 for details). On the whole, the lid retained the best physiologic control, followed by adduction of the globe (Figure 23-8). Pupillary reflexes to light were poorly preserved, and the residual reflexes seemed to come and go in different parts of the spontaneous cycles: during the spastic phase the pupil was unresponsive to all stimuli, but during the paretic phase weak reflexes could be elicited (Figure 23-9). Accommodation was difficult to measure in these cases because it kept changing with the cyclic spasms and because the acuity was often poor; besides, some of the children were quite young. Accommodation could not be measured thirteen times, and was not mentioned seventeen times. In nineteen patients it was reduced or lost, and in five it was present. It has often been aid that vertical gaze is entirely lost in these patients, but this is not true: down-gaze was quite extensive in a few (numbers 2, 13, 25, 32, and 57), and slight up-gaze also was possible occasionally (Figure 23-8). Adduction varied from none to fairly good, and abduction was normal except in ome patients who had undergone squint surgery. The fourth nerve was almost always intact. 110 100 Figure 23-8. Amplitude of re idual physiologic movements and of cyclic movement in patients with cyclic oculomotor palsy (cases described in Table 23-4). The column represent averages of all patients for whom information was given. For the pupil and the lid there were fifty-five eyes (fifty-three unilateral cases and Rampoldi's bilateral case). Accommodation wa not included in this graph because it was too often inadequately de cribed to allow comparison with the other movements. Values are expressed as % of normal range. The average cyclic pupil contractions were larger than the normal range (103%), but all other movements were less extensive (values on the ordinate le than 100%). ote that for the pupil, the lid, and the medial rectus the average cyclic contractions were larger than the re idual physiologic movements, but there were no cyclic up or down movement at all. (From I.E. Loewenfeld and H.S. Thompon, Survey Ophthal., 20 (1975):81) I ,-. I T A z ~= ~ 90 "' ~ 80 U 70 8 ~ 60 [ill= t PHYSIOLOGIC MOVEMENTS CYCLIC MOVEMENTS B :'::: 50 a: 5 40 "' ~ 30 C o! __, 20 ..., ;c, ... <-. 10 0 .,. 0 Limi (55 PUPIL eyes ) (55 LID eyes) ---~-~- ADDUCTION -( 54 eyes) GAZE ,L. (52 eyes) GAZE t (53 eyes) 1068 Table 23-5. IV. Pupillary Pathology: Symptomalogy Attempted quantitative analysis of physiologic functions LID (PTOSIS) % ADDUCTIO % UP-GAZE % DOW -GAZE % ACCOMMODATION % PUPIL marked ptosis 20 limited 30 limited 30 limited 30 poor 20 could not measure ? less marked ptosis 40 abolished 0 abolished 0 abolished o poor 20 could not measure ? ptosis 0 reduced 30 slight 20 almt:>st normal 90 n.s. normal 100 markea ptosis .!0 aoo1Lshed 0 abollShed o very ooor 10 uxea O n.s. no voluntary iii.ting 0 paralytic O paralytic O paralytic o fixed O paralytic 0 full; no voluntary 1irting 0 poor 20 none O poor 20 fixed 0 ? (amblvooic) ? incomplete ptosis 25 poor 20 abolished 0 abolished O fixed O reduced 3 30 incomplete ptosis 25 ,1.1.xHLShea O aoo1ished 0 aoo isnea o n.s. n.s. (amblyopic) ? almost full ptosis 10 slight 20 none O slight 20 fixed O reduced 30 11 slight ptosis 80 paralyzed O paralyzed O paralyzed O unreactive O n.s. 12 slight ptosis ~0 paraiyzea 0 paralyzed O paralyzed o tixed o n.s. 13 t to almost normal 90 quite good 90 verv aetective lu ouite good 90 reacted 60 n.s. 14 complete ptosLS O paralyzed O paralvzed 0 paralyzed o fixed O unclear statement ? 15 almost flaccid ptosLS 10 only 1 mm 10 absent 0 absent 0 slight 20 oaretic 30 ? 16 full otosis ~ 0 paralvzed * 0 paralyzed 0 paralyzed O none O ? (amblyopic) 17 P.f. 7mm 70 23° squint 20 paretic 30 paretic 30 fixed 0 n.s. 18 marked ptosis 20 paralvzed O i:arruvzed O paralyzea O fixed O n.s. 19 partial ptosLS 60 up to midline 50 aoo1ished O a.001isnea O unreactlve O unpaired ~u 1 20 no vol unta rv raising *t-,od-;m~u:::c:rh::r':::e':::sitr=-1i-:'c:.t:::e:.--a-h~i-i. vd""'a"1°=:m='o';:-s~tr.:n':co-=n"'e,---+....,;5l -::m=u:;c..;:::nr=-e=-s=-; t".r"'1-=c=rea,-+-,.!,.;;.. o ht=::rc:a'=c'=e===---t-,5a-l~n=-o':'itS:,c::", 1r:,e~a::r:-----+-,,-.t, 7 21 incomolete ptosis 25 2 mm .io axuished O ano•ished O fixed O not clear ·t 22 almost total ptosis 10 absent 0 absent 0 absent O unreactive 0 n.s. 30 23 incomplete ptosis 25 paralyzed O paralyzed O paralyzed 0 slight 20 paretic 24 paralytic ptosis O almost paralyzed 5 paralyzea O parruvzed O none O n. s. 25 partlru pr.os1s ou llmitea 112 50 absent o limited 1/2 50 + in flaccid ph.30 ? (amblyopic) 26 o.f. 5 mm 50 SL past midlrne oo absent o n.s. - fixed O n.s. (amo1vopic) 27 incomplete ptosis 25 sl. past midline 60 absent O absent O absent O ? 100 slight ptos1s * 80 just past midline* 60 absent O absent O incxtensivc 30 normal (10D) 100 29 oartial otosis 50 limited 30 limitea 30 limited 30 unreactive O normal 0 30 total ptosis 0 paralyzed 0 paralyzed O paralyzed O tixed o absent (amblvopicl { 31 full ptosis • 0 paralvzed * O oara ,vzed O parruvzed O sliP-ht 20 present (unclear) 32 partial ptosis 60 poor 20 absent O slightly imited 80 reduced 30 decreased 33 flaccid ptosis O paralyzed O absent O paralyzed O unresponsive O n. s. (amblyopic) t-3,,,4.-- __fl_ac_c-,i:--d~pto_s_1_· s____ ....,,..,o,... ,~zea O para, vzect u para vzea O tixea O n. s . 1 7 35 p.f. 3 mm 30 poor* 20 none O none O trace 5 n.s. (amblyopic) 36 almost full ptosis 10 limited 30 limited 30 limited 30 n.s. - n.s. (amblyop1c) 70•+-:c-::par::.:;:-r,.,_,_v:':cz::-'.e;::,d:r''-"--'t-'3~7:;-l--:'c'=an'='-'1;--;if'it~6"'m='me==:a:.....---+-i6~0;;-l--'a1m~~o::::s~t-n:-:o-:n-:ec---+~5'""l-;2Frnm"==---+iz2.;;o-l--':a1m:;:::::,o::s::;t:..,n::-o::-n::-e=---l-:'.:.;;5'..+-:'m::.lhl;::. ,.;.-=m=-,al::-.---h1 38 paretic lid 30 none 0 none 0 none O slight 20 n.s. (amblyopic) 39 flaccid lid 0 paralyzed 0 paralyzed O paralyzed O reduced 30 n. s. (amolyopic) 1 ~n~o-n-e~-------il----,0,1 ~v-e-ry-.-lrm,..._ 1 nonreactive t-4"70=-1 __n_o_v_o...,l:--u-n""'t_a_rv_c_o_n.,...tr-o....,l,---t--,0::~ite;--i~d---f~l~ u· •--'-v-e-ry---'1.-,im-,~t-e~a--1---,l--,0,.. O none u u 41 P.f. 3 mm 30 limited 30 limited 30 limited 30 tixed O none 1 -"p""a---r""al-',-y:.......z_e~d--+---'--:-o-•----'p---ar---"-al.,,-y---z-e-d~------,o;-1 lixcd 1--4-i'-2:'--I -""'-'p.""f"'" . ...;3,....;;;;m=m-'--------+-30--0,,..-l-'p;__;a:crccal:..;,ccy..:.z_e_d~----+-_;;__,o,.... O n. s. (amblyopic) - n.s. 43 ptosis u n.s. - n.s. n.s. - n.s. 44 full ptos is O just past mid_::l::.:i::.:n:.::e-----1-6..:....:.0_ __ ..._....:0:....... ___ +--_o.,... O n. s. 1_n=o=--=ne::..,...._~ 1_:nc:.o:..:ncce::..,...._...,..., 1 fixed ? 45 almost full ptosis * 10 paralvzed * 0 paralvzed O paralyzed O ooor 20 ? (not measured) ? 46 p.f. 3 mm 30 none 0 none 0 none O ver, poor 10 ? 47 complete ptosis O e__aralyzed O paralyzed O paralyzea 0 1ixe O n. s. (amblyopicl 1 ~ai.....,....m-o~s~t-n_o_n_e_* 5 ,__4_8_,_c_o_m_ ....,..ple_t_e~p-to_s_1~·s---+-~0· rumost none 5 very little 10 1ixe O none (amblyopic) 1 u 50 como1ete otosis O none O none O none O lixc O none (amblyopic) 51 ptosis* 0 limited(surg;ery)* 30 none O none O wea· 20 n.s. ■-5~2-•-~c-o_m_m_l_e_t_e__ pto_s_i_s---+--0-•_n_o_n_e~* 0 none 0 none O lixed O n.s. 53 full otosis O to midline 50 n.s. n.s. n.s. n.s. 1-~n~o..cn~e-----+-o;s-·l-=n~o=n~e-------lf--no-•-~sl~i 6~n7t-----t-n2nocl l--5~4~•-~fl~a"'c---c~i~d~l~i~d:--------+-o;;...1...:a1m::.:,....=o=s~t~to=m--,i'dl~in~e--1~..;-;4,0~ n.s. 30 55 up to 7 mm 70 can adduct 40 very poor 10 poor 20 1 mm 30 reduced 1...:s:::;l;;i~gb 7t=a::;.,dd;,:u=-=cc:;:t-,-io::-:n=-~h1 70d ·-::n,:o'=n"=e,-,:.==----t-=-oi,-·l-::n-=o-=n-=e-----~i-=-i.o+-=s1:nir::gr.ht---+;;2,;o~ I could not measure ? l-~5~6-l~c:1:an:....:::::..r..:a.,...is!!e~l:,.id.-s"Tl~ig-,lhcc,u=y--+""'5;,..0~ 30 57 slight ptosis 80 past rnidline 60 limited 50 quite good 80 quite good 80 impaired /; lR lL 2 3 5 6 8 9 10 ,j/, = individual case numbers (see Table 1); % = quantitative estimation in terms of full range of physiologic movement; n. s. = no details g1".en about function; ? = function mentioned but no quantitative statement given;*= surgery for ptosis or for squint, as indicated; p.f. = palpebral fLSsure; in estimations, voluntary control in flaccid phase was considered, 23. Special Oculomotor Syndromes Table 23-6. # / 1069 Attempted quantitative analysis of cyclic movements LID % cvcled extensively cvcled less limn rm:ht eve scmiotosis - almost normal p.f. 3mm -almost normal full ptosis -normal opening full otosis - no cycles ~ partial otosis no cycles dcscr . 8 partial ptos is no cycles descr. 9 did not cvcle 10 slight ptosis no cycles 11 12 sl i<>"htptosis no cycles slirrht otos is -+ slirrht cvcles 13 14 flaccid -.normal ·naccid-9 mm 15 cvcled (no numbers given) 16 17 P.f. 7 mm -+-12 mm(> n) 18 nm:-al vtic -+- lifted 19 oartial otosis-lifted 20 droooine:-ooen 21 p.f. 5-6 mm -lifted 4 mm 22 full otosis ➔ incomolete Ptosis 23 partial ptosis did not cycle 24 marked ntosis - o. r. > norm al 25 partial ptosis -slight raising 26 P .T. 5 mm - normal 27 p.f. 5 mm -fully open 28 slight ptosis -retracted 29 partial ptosis - no cycles descr. 11111 otosis-norma.t openinrr 30 31 almost full ptosis -retracted> n 32 partial otosis-rctractcd >n 33 flaccid-lifted strongly 34 flaccid-lifted 35 p.f. 3 mm~8-9 mm (ps.vG) 36 semiotosis - normal 37 n.f. 3-6 mm - no cvclcs 38 naretic-. normal 39 flaccid -+-oPen 3/4 40 flaccidretracted Ins.VG) 41 n.f. 3 mm - no cycles 42 p. f. 3 mm -+- normal 43 otosis-+ opened 44 ptosis - fullv onen 45 P.f. 3-4 mm__.retractcd >n 46 p.f. 3 mm-normal 47 ptosis ~reiractcd >n 48 complete ptosis - normal 50 olosis constant - no cvcles 51 otosis-. >n \Vith ps. vG 52 comnlctc ntosis -.wide ooen 53 full ptosis-75 % up 54 11accid - retracted with os. vG 55 P.f. 3 mm-..7 mm 56 o.f. 4 mm-.10 mm 57 70% open -retracted with ps. vG lR lL 2 3 5 - 80 50 50 70 100 0 70 lU 0 0 0 20 100 90 50"' 50 80 50 80"' 40 50 0 120 20 60 60 50"' ?0 100 120* 60 100 80 80 70 0 80 70 120 0 80 80 100 120* 80 120 100 0 120* 120 75 1.::0 40 60 50 ADDUCTION adduct. shortof midline adducted slirrhtly intermittent innervation n.s. rolled in lo midlrne rollcct in aboul 1/2 no cycles described no cycles described did not cycle no cycles dcscribea no cycles described no cycles described some adduction no cycles aescribed no cycles described 23u ~ 190 abducted globe adducted eye roffea to mid! ine did not cvcle rolled sl irrhtly past m idl. s!irrht adduction did nol cycle no cycles described moved in in soastic ohase eve rolled in rolled sl. oast midlinc no movement no cycles describea rolled in short ol midline no cycles described no cycles described no cycles descri6ed no cycles described exo 40--=45"- exo 5-8u movea in to midline no cvclcs described rolled in to midi ine no cycles dcscrl6ea divere:ea-+ almost midl. did not cycle rolled in 4-5° n.s. to moderate adduction rolled in slightly rolled ill s1igfitly no cycles described rolled in to midlinc rolled in verv slightly 25v exo-+ 10° eso no movement exo-to midline rollen in to midiine 150 exo - to midline .:uu exo no movement no movement % 40 20 30 PUPIL max. mvdr. -.max. miosis cycled less than right eye enlarged-+contracted 6-8mm-.3mm 50 normal-< normal 50 9mm-3mm 70 6 mm--.1.5 mm ?0 maxunal size-2 mm 0 9 mm-+-2.5-3 mm 3 mm ?0 5-6 mm-+-2.5?0 less extensive than IFI0 "?0 5 mm-l.5 mm 30 7 mm-2 - 2.5 mm 'tO 8 mm-+-3 mm(< n) •o 8.5mm-+-3mm (<n) IO 7 mm-3 mm(,( nl 30 8 mm-3 mm 50 • atcd ..... contracted 0 6 mm-1.5 mm 60 7.5 mm---.1.5-2 mm 20 9 mm+3 mm 0 8-9 mm-+-2-3 mm ?0 max. mvdr. _.miosis 30 6-7 mm-.2.5-3 mm 50 8 mm__.4 mm 60 5 mmextreme miosis 0* 7.5 mm-..4 mm ?0 mydriasis + miosis 40 mvdriatic-+markedly miot. 0* 8 mm - 2 mm ( < n) ?0 7.5 - 8 mm+ 2.5 mm ?0 5 mm-+-3 mm ?0 8 mm~2.5 mm •W 8 mm-3 mm 50 mydriatic<n ?0 9 mm__..2 mm 50 5.5 mm-+-2 mm ?o 7 mm..,.3.5 mm 40 ver.v largecontracted 0 6 mm-+2 mm 10 very large-2 mm - max. mvdr.ma'C.miosis 80 larrre-+- marked miosis (<n *20 8 mm-. 3 mm (<n) 20 5-6 mm-full contraction ?0 8 mm+ 2 mm •50 7 mm-1.5 mm 10 7 rnm-2.5 mm •60 6 mm-2 mm *0 mydriasis -+miosis 50 mydnas1s - normal 50 5-6 mm-1.5 mm 50 8 rnm-3 mm(<n) 0 9 mm-3.5 mm ( <n) u 5 mm--.2 mm - % 100 50 100 100 1.::0 120 100 120 120 100 50 60 100 120 120 100 120 100 100 120 120 120 100 80 80 100 50 100 120 120 120 50 1.::0 100 120 120 100 80 100 100 120 120 120 120 lUU 120 120 120 100 100 lUU 100 120 .l"U 80 ACCOMMODATION ++ near ooinl moved in ++ near point moved in no cycles mentioned n.s. 6D paralvtic - 6D accomm. 3D 2.5D--. 5.5D myopic ·ru no cycles dcscrilied n.s. 3D -4D--. -ID ? could not measure 3D + 3D+ +6D emmetr.marlced mvoD +++ ZJJ + 5D-+ 7D 3D + 3D in spasms 0 did not cvcle n.s. n.s. + 3. 5D accommodation 3.50 + 3D in spasms 3D + 6D in spasms 6D 8D increase in soasms SD + ID during: spasms 1D ?0 no cvcles described ++ contraction of ciliarv m. 6.5D -3.5D-+3D -3D-+3O 6D no chanrre in cvcles 0 no cvclcs described ?0 absent- no cvcles descr. 0 increased 8-10D in spasm 9D weak cycle , 2-3D 2.5D accomm. participated ++ sJirrnt increase in spasms + cycled about 3. 5 D 3.5D cvcled over 4-50 ranrre 4.50 near ooint aooroached ++ participated in cycles ++ not mentioned -4 D-. + 3D 7D cycled over 2-3 D rane:e 2.5D -3D--. 0.5D+ 3.5D n.s. cvcled lD 1D increased 2D in spasms 2D ] I) rncreased 10 in soasms + 4D in spastic phase 4D n.s. + 4D in sPastic nhase 40 cycled over 7D range 7D n.s. could not see cvcles 0 n.s. cycled over 2-3D range 2.5D mcreasea 111 spastic phase++ cyclea about 2.5D 2.5D - - - - - - I # = ind1v1dual case numbers (sec Table l); %= quantitative estimation in terms of full range of physiologic movement: 120 = larger than normal excursion; n.s. = no details given about function; ?0 = function described but no cycles described;*= surgery (for plosis or for squint as indicated);p.f. = palpebral fissure; ps.vG = pseudo-von Graefe phenomenon: lid stayed up on gaze down in spastic phase; in estimation~ range of movemeni, condition in flaccid phase, and surgery were considered. ' 7 J 1 2 ---------Tl 6~-- 3 .\ - . \ -0----~ ~,-/----t 5 ~\ . , ..--'-, I . 4 /_,,-- -,----,- . _,' , ' \J ~ 3 \ , d I 0 d 6 7 5......:: .:\---,,,~ '\ ,,,, 4 ,-\: ...,,: -.\- ___,,,,,.-- \ / \ r.../ I d I ,,_. I , d 30 40 50 :1 I d 20 9 10 --- -~,::. ____ \' __ ~---~\,~ / __ ~ ,1 / \I/,., \ ../ d I d I 35 11 ~ \+--- ' ,,,, ~-/ \I ' \,,/ I I d 40 d 45 GO 70 Phase 1 I 40 50 GO 70 80 1:' 100 00 110 120 130 120 130 Cycles Full V, ~2 ..0 61 ::I Zo 0 1070 10 Seconds 20 30 40 50 60 __ Figure 23-10. Durations of spastic phase (top graph), of paretic phase (middle graph), and of full cycles (bottom graph) in cases described in the literature (Tables 23-4). In each graph the ordinate shows number of patients, the abscissa duration in seconds. Note that the spastic phases were on the whole shorter than the paretic phases, with relatively wide interpersonal variations. (From J.E. Loewenfeld and I I.S.Thompson, Survey Ophthal., 20 [1975]: 81) Flaccid 30 _,. I was slightly smaller than the left at the start of the record, and it contracted feebly to light. Shortly after the first light reflex it began to take a turn downward, and then went into a spontaneous spastic contraction which lasted about 14 seconds. During this time light stimuli failed to elicit light reflexes in the intensely miotic right pupil. After the twenty-fifth second of the record the pupil redilated gradually and its light reflexes returned. (From I.E. Loewenfeld and H.S. Thompson, Siirvl,Y Ophthal., 20 [ I 975J: 81) Spastic Phase 20 ,,, '· 8 I 30 d I - ;/:j:::_ \, ,_,/ -~ I I Figure 23-9. Intermittent light stimulation during a pupillary cycle (Burian and Van Allen's patient, Iowa City, Iowa; case 48 of Table 23-4, recorded by H.S. Thompson). The solid line represent the pathologic right pupil, the broken line the normal left pupil. The top and bottom line are continou . The test was done in darkne while the patient looked at a dim red fixation point about 6 feet distant. During the times indicated by the frames the patient's normal left eye was exposed to 1-second, bright light flashes, while the right eye remained in darkness. The right pupil 10 ,, \..,/' 15 ·: ,,, 25 seconds-+ o . _\_ ,t' '', , 'v' d 10 8 \ 3 1 \ -\--,'--- ,' I"'I d 6 20 . -\---,~ ..~ =\---,,,,,..::.=_ , \,. ,' I 5 7 10 5 \ 1 1 ,, ,,,' , -\--/-- 2 21- 4 70 80 90 100 ( average values) 110 1'0 100 160 170 23. Special Oculomotor Syndromes / 1071 A 1 missed _j r cycle 111111111 1111111 34 35 B I 37 nLJ fl nL missed cycl0 L_J I II 0 1111111 36 I 2 II II I 3 1111 !missed cycle LJ • 111111111111111111111111 4 5 6 7 8 Figure 23-11. Timing of cyclic movements (patient 45 of Table 23-4). The patient (in dim light) looked at a small, dim red fixation point about 6 feet distant. One observer watched his right eye and indicated the moments when the lid lifted spastically and when it again began to droop by saying "up'· and "down," respectively. A second observer noted these times, using a watch with a large sweep second hand. A and B were identical experiments, done on different days. In the graphs line up denote lid spa ms and line down, paresis. Three times a cycle wa missed because the patient became inattentive and looked around. Note the irregular timing from cycle to cycle and the similarity of the general time pattern on different days. (From I.E. Loewenfeld and H.S. Thompson, Survey Ophthal., 20 [1975]: 81) ------------------------------A 10 t II ------~ \_/~r-~.'~----------- a ____ \J \ 12 10 II ----------C·---------------------~----------------------- IO 11 12 13 14 1!5 16 17 18 19 20 21 22 23 24 seconds-+ Figure 23-12. Smooth and uneven cyclic movements ( cases 48 and 45 of Table 23-4). Solid lines represent the right, broken lines the left pupils. The room was dark and the patients looked quietly at the far fixation mark. A: Smooth, extensive spastic constriction of the right pupil of patient 48 when he was 7 years old. 8: Large but uneven contraction movement of the left pupil of patient 45. C: Smaller contraction is patient 48, which was recorded later in the same experiment as A. At the beginning of C the child was sleepy and his pupils were smaller than in A. The right pupil became exceedingly tiny during the spasm and then redilated gradually. Note the unevenness of the relaxation which was interrupted by many irregular little contractions. (From J.E. Loewenfeld and H.S. Thompson, Survey Ophtha/., 20 (1975]:81) 1072 / IV. Pupillary Pathology: Symptomalogy fibrillary twitches before it lifted, and the pupil would contract in a series of irregular little dips before it became spa tic (Figure 23-12,B). At the end of the spastic phase, also, relaxation would occur irregularly, with many little dips and flutterings (Figure 23-12,C). While the cyclic movements were extensive, they were slow: the peak speed of the spa tic pupil contractions was much lower than that of light reflexes, and even lower than that of the inextensive residual light reflexes in the bad eye (Figure 23-13). There was an inverse relation between the amplitude of the cyclic and of the physiologic movements: patients with well-pre erved physiologic control tended to have weak pa tic movements; and the reverse was also true. Patients with relatively good voluntary lid movements generally had less intense cyclic lid retraction than tho e with flaccid ptosis; patients with pupil fixed to Jjght and to near vision had larger cyclic pupil changes than those with residual phy iologic reactions; those who could adduct their eye fairly well did not have much in-rolling of the globe during the spasms; and in those with good accommodation there were only minor accommodative changes during the cycles. But vertical eye movements did not conform to this rule: even though vertical gaze was very poor, cyclic up and down movements were never observed. pupil was already small, the miosis was prolonged on looking near. This kind of influence was found in varying degrees in many patients (see Table 23-7). Accommodation-convergence efforts increased the extent and duration of the spastic phases. Attempted vertical gaze or forced lid closure had the same effect. Conversely, abduction efforts shortened and reduced the spasms and accentuated or prolonged the paretic phase. These influences of voluntary gaze efforts upon the cyclic movements did not appear immediately but only after the effort was maintained for several seconds. Attempts at innervating the extraocular muscles thus did not bring about normal voluntary eye movements, but they modified the involuntary cyclic movements. There was no apparent correlation between the extent of the patients' residual voluntary oculomotor control and the degree of this indirect effect: in patients with poor voluntary eye movements as well as in those with extensive ones attempted third nerve innervation could have a strong influence upon the cycles, or no influence at all. Similarly, there was no apparent relation between the spontaneous rhythm of the cycles and the influence of attempted eye movements upon them: both in patients with fast and in those with slow cycles there could be marked modification by voluntary gaze efforts, or none at all. 5. Influence of Attempted Eye Movements on Cyclic Activity 6. Influence of Physiologic Conditions and of Drugs (a) Sleep, Arousal, Physical or Emotional Stress, and Systemic Drugs The degree of alertness influ- In Rampoldi's first patient near fixation seemed to encourage the spastic phase. When the child looked at one of her toys nearby, the pupillary dilation was less marked than when she looked far away; and when the enced rate and amplitude of the cyclic movements. While they continued during sleep, they were much 91-~,,-_-,-,_-----------A----------------\1•--e--ll--------~ 8 ~-~~~~,--------------------------·~~-----1----------1 7 ,________ -,~s¾;=========::::::==========-~-;-;;-~ ~, , ___,,,.,,, ~ \ :-.,~........ -- ~ -- L_ _______ ,..- _ ........... 61---------'~,~~~ 5 1-------------'~...., "~ .... ~_"" _______________ _, ',, ............... .......... '--... 4 1------------1.-2~8--~---,---,, mm/sec. i 3 ~ 2 _:...,,, Figure 23-13. Peak speeds of spontaneous cyclic contraction movements A and of light reflexes (B) in patient 45 of Table 23-4. In A the eyes were in darkness. The normal right pupil (solid line) remained quiet at about 7 millimeters, while the left pupil (broken line) contracted extensively during the spasm. In B the left pupil was in the paretic phase, and it was larger in darkness than the right one. During the time enclosed in the frame the right eye was '--....______ ~-~ exposed to a I-second bright light flash. The normal pupil contracted quickly and extensively, the pathologic pupil much less amply and more slowly. The peak speeds of these movements are indicated by the thin broken lines. Note that the spastic contraction, though large, was slower than even the poor light reflex on the affected side. (From I.E. Loewenfeld and H.S. Thompson, Survey Ophtha/., 20 [ 1975]:8 I) 23. Special Oculomotor Syndromes Table 23-7. CASE .....JL- 1 -23 ---r- 6- 8-9- ---rr11 _ 1_2_ 13 ---r,r15 ---rs17 18 19 20 ---rr22 23 ----zr~ 26 ~ 7'i!" 29 ~ 31 32 ~ ~ ~ ~ ~ -38 -~ 40 ~ 42 43 ~ 45 46 ----:rr- ~ 50 51 -2.L__ 53 54 55 _ 56 5_7_ / 1073 The effect of attempted extraocular movements on cycles DESCRIPTION near fixation favored SEastic phase volunt~ ere movement efforts did not block crcles cycles became slower and less extensive in abduction; spasms were enhanced by adduction n.s . cvcles were frozen in mydriasis by abduction , in miosis bv adduction cycles were not affected by light or by attem.12ted convergence-accommodation n.s . adduction and convergence induced or Erolonged miosis; abduction blocked miosis miosis became faster and more extensive with convergence eITort miosi s was maintained on attemEted adduction and while reading c,y:cles were affected b;):'.: convergence , accommodative effort , and l:!ght adduction and abdu ction had no influence; near effort hastened miosis convergence 1 adduction 1 S2-or down-gaze sEeeded ?lcles 1 favoring SEasms ; abduction h3:d n_o effect ab - or adduction had no effect ; light 1 near effort and hd-<:lose shortened and retarded mrdrias1s adduction delayed or aborted mydriasis n. s . light and attempted accommodation did not affect cycles convergence , adduction and up - gaze l en" ,nened spasms and reduced amplitude of mvarias1s ,add11 ction lengthened s2 asms ; abdu ction shortened them convergence , attemEted EOM had no effect; forced lidclose and light retarded mydriasis attem12ted adduction and abduction and forced lictclose had no eITect addu cti on and convergence froze crcles in miosis; abduction retarded miosis adduction tended to cause m iosis abducti on mvdriasis , but cycles never stoooed convergence &adduct . aborted flaccid stage . prolonged &increased miosis; abctuction prolonged mydriasis adduction prolonged and increased miosis; abduction favored mydriasis adducti on, u12 - or down-gaze increased miosis; abdu ction increased mydriasis; timing not aneeted statement unclear n. s . adducti on uo--!<aze and lidcl ose increased &orolonged miosis; abduction reducecl & sliortenecl it adduction, convergence and lidclose favored miosis; abduction favored mydriasis addu ction 1 UE-gaze caused sjasms; abduction aborted s12asms attem2ted adduction hastene sEastic Ehase light, attempted accommodation-convergence , up- or down-gaze had no effect on cycles n.s . adduction, convergence &lidclose prolonged & enhanced miosis & reducecl myclriasis; abduction tlie reverse adduction tri P-P-ered & prolonged miosis; abduction hastened and maintained mydriasis no influence of extraocu lar movements observed n.s . extraocular movements did not affect cr cles adduction and abduction did not affect cycles adduction triggered and maintained SEasms; abduction maintained flaccid phase efforts at adduction hastened and increased SEastic Ehase no effects of extra.ocular movements noted volu nt~ ere movement efforts did not influence rate of crcles n.s . adduction and near fixation 12rolonged spastic phase; abduction prolonged paralytic phase n.s . c,y:cles Eersistcd during following movements- - statement not clear n.s . adduction triggered s2astic 2hase ; abduction aborted s2asms could abduct ere during s12astic 12hase without altering ercles adduction triggered and prolonged soasti c phase ; abduction favored oaralvtic uhase no certain effect of intended eye movements on t i ming and amElitude of crcles adduction and near effort triggered spasms;effectofup- or down - gaze and abduction uncertain CODE _ 5_0_ 0 75 -- 100°" ~ 100°" ----,-g-100°" ~ ~ 50 25 100 0 ~ 50 25 0 100 75 ~ ~ ~ - ~ 50 ---roo- ~ - -0- --75 Tcio ---0---- - - 0- - 0- - Tcio ----rs- - 0- - -- ~ -- --- --Too - 0- 100 - 0- - --100 CODE= quantitative estimation of influence of intended eye movements on cycles : - = not tested or reported; 0= none; 25 = only some movements effective , others not; 50 = influence on amplitude only or on timing only , or influence not marked; 75 = influence on ti.ming and amplitude , but cycles continued; 100= adduction, convergence-accommo- dation, light, up - or down-gaze or forced lidclose triggered miosi s and aborted mydriasis; and abduction main tained flaccid phase . 1074 / IV. Pupillary Pathology: Symptomalogy Table 23-8. The effect of physiologic conditions and of drugs on cycles { -3- CONDITION # sleep 28 fatigue emotional excitement 2 9 { -3- mental stimuli acceleration of 12ulse and respiration body position (prone or standing) running increased blood pressure pressure on homolateral carotid arteri chewin~, innervation of frontal muscles systemic drugs: anesthesia 1 7 -21 -13 2 1 { -2- intravenous adrenaline _prosti_gmine - - - - - - - - dilantin phenobarbital caffeine----------- -librium ------. reserpme --- -- -- - -- "tranquilizers" --2- -1-1-y - 1-y ------------- - ·12 EFFECT ON CYCLES _ c_ycles continued _____ C.}'.Cles stoE:eed C.}'.cles slowed _ cycles accelerated; ___ s:eastic :ehase increased cycles accelerated no etfect no effect no effect no effect no effect no effect _ cyyles continued _____ _ c_ycles stoEped ______ no effect no effect - no effect - no eifect - - - - - - - - - no effect - no effect --no effect no effect #=number tried by various authors. slower and less extensive than when the patients were awake; and in deep anesthesia they ceased altogether. Conversely, they accelerated, or the spastic phases were increased, when the patients were aroused by mental or emotional stimulation. In contrast to this strong influence of the level of arousal, maneuvers to change the cephalic and ocular blood pressure and flow-such as head-down positioning, acceleration of pulse and respiration by forced breathing, running or jumping, or pressure on the homolateral carotid artery-failed to alter the rhythm of the ocular movements. Intravenous injections of adrenaline and administration of systemic drugs in small doses also had no effect (Table 23-8). (b) Drugs Instilled into the Eye Many tests were done with locally instilled drugs. Atropine was used fifteen times, homatropine twice, cocaine twelve times, eserine fourteen times, pilocarpine nine times, and adrenaline four times. It was found that atropine and homatropine dilated the pupil in the normal way and abolished the cycles. Cocaine also dilated the pupil but the cycles continued, though less extensively than before the drug was given. Eserine and pilocarpine constricted the pupil and flattened the cyclic movements. When these drugs caused maximal miosis the cycles were suppressed. Adrenaline had no influence. The local drug effects pertained to the amplitude of the cyclic movements, but their rate remained unchanged. 7. Clinical Course Once established, the syndrome seems to remain unchanged for many years-in fact, as far as is known, throughout the patient's lifetime. In some cases surgical procedures were done to correct the ptosis and the exotropia (see Table 23-4), with variable success. So far no case has come to autopsy, since the patients tended to outlive their ophthalmologists and, having become used to the chronic defect, were lost from view. Because of the stationary nature of the condition intensive testing with invasive procedures is, in our opinion, not indicated. D. Localization of the Lesion and Mechanism of the Syndrome 1. Historical Views Rampoldi (1984) suggested that the syndrome might be due to bouts of hyperactivity of the sixth and seventh cranial nerves as well as the sympathetic innervation, in the presence of an old third nerve lesion. This idea was soon dismissed because the sixth and seventh cranial nerves and the sympathetic supply of the eye were found normal in almost all cases. It was quite clear that the eye movements were due to alternate spasms and paresis of the muscles innervated by the third nerve. But where was the lesion located, and how did it bring about the peculiar cycles? There were two main trends of thought in regard to each of these questions. One group of authors believed the site of the injury to be the efferent oculomotor fibers (Table 23-9,A). A second group maintained that it was Table 23-9. Assumed site of lesion A EFFERE NT OC ULO MOTOR FIBERS YEAR 1900 1901 1903 ~ 1913 1913 ~ 1923 1924 1945 1973 AUTHOR Bechterew Axenl'ela & Schlire nbe rg Bielschowsky Salus Herbert Lauber v. Hippel Salus Kubik McGregor Burde ASSUMED LESION basal disease process damage to third nerve - but nuclear lesion also is possible damage to 3rd n, roots near exit from midbrai_n; pe~haps_ also nuclea~ . interruption ot 3ra n. tibers near exit from m1ubram, with faulty regenerat10n basal lesion oI thira nerve third nerve involvement, basal or in brainstem partial third nerve lesion with misdirection of regen~rated ~ibers aamage to ocuiomotor roots with aberrant regenerat10n or 11be_rs lesion of 3rd n. near exit from mianram,wnn talllty regenerat10n damage in nucleus or its efferent patlis infranuclear lesion - peripheral thira nerve palsy B OCULOMOTOR NUCLEUS OR SUPRANUCLEAR PATHS YEAR --1893 1906 1907 1913 1913 1914 1914 1924 1927 1928 1929 1930 1931 193 1 1932 1932 1935 1937 1939 1941 1942 1945 1949 1963 1970 1970 1973 AUTHOR ASSUMED SITE OF LESION partial nuclear damage Fuchs partial nuclear lesion Fromaget probably nuclear lesion, including 3rd n. fibers near exit from midbrain Levinsohn nuclear uamage Greeves . perhaps nuclear mechanism Uhthoff degeneration, probabli in Westphal-Edinger nucleus Zamorani cortical lesion "most likely mechanism" Groethuysen oamage or aplasia of 3rd n. nucleus, sparing rostral part Behr lesion in thiru nerve nucleus Veil lesion ,erobabl_y in oculomotor nucleus_ . _ . Frigerio main lesion nuclear & su,eranuclear, with ,eartial loss of 3rd n. fibers m some cases Bielschowsky ,eossibl_y ,eartial damage or a,elasia of nucleus and centri,eetal ,eath Selinger Petrovic & intermittent loss of function of oculomotor nucleus Tschemolossow partial degeneration in 3rd n. nucleus with sparing of rostral are a and interruption Stein of supranuclear path same opinion as 1929 Bielscliowsky :eartiaI lesion in oculomotor nucleus Mak van Waay lesion "in the region of the third nerve nucleus'' Bielschowsky lesion primarily in third nerve nucleus, sparing caudal part, with offshoot of Hicks & Hosford lesion interru,eting su,eranuclear ,eathwais Bielschowsky lesion must be near third nerve nucleus Bonnet :eartial nuclear lesion, including connections to supra- and infra-nuclear paths Lowenstein & partial lesion of oculomotor nucleus and of supra-nuclear connections Givner McGregor dam~e in oculomotor nucleus or its efferent paths Duke-Elder partial lesion of third nerve nucleus with caudal area spared; perhaps also su,eranuclear defect Burian & partial destruction of oculomotor nucleus and of supra-nuclear connections Van Allen Crone & Horsten partial nuclear lesion, and disturbed supranuclear and reflex transmission, with irritative focus nearbi Morizane & partial destruction of 3rd n. nucleus and some adjacent supranuclear structures, Uemura s,earing connections to "near convergence center" partial lesion or aplasia of oculomotor nucleus, combined with supranuclear Clewett-Price defect & Trounce located in the mjdbrain, affecting the oculomotor nucleus wholly or in part, and interfering with its supranuclear connections (Table 23-9,B). The cyclic movements were thought by some investigators to be related to vascular mechanisms (Table 23-10), while others believed the cycles were due to periodic discharges of the oculomotor nerve (Table 23-11 ). We summarized the chief arguments brought forth in support of these theories in 1975 (Loewenfeld and Thompson), and for reasons of space must refer to this publication for a full discussion of the matter. After considering all facts and assumptions we concluded that the "vascular" theories were outdated, or rather, that they had lacked proper physiologic and pathologic support from the start. But both the "peripheral third nerve" and "nuclear" theories were based on a number of good arguments. Most important among these were the following. On the one hand it appeared difficult to explain the total, unilateral third nerve deficit on the basis of a nuclear lesion: how could the pathologic process pick out the oculomotor subnuclei to one eye only (on both sides of the mid line) in so many cases, and leave those for the other eye intact? Furthermore, involvement of additional cranial nerves, ipsilateral to the third, was found in 1075 1076 / IV. Pupillary Pathology: Symptomalogy Table 23-10. Assumed vascular mechanisms YEAR AUTHOR MECHANISM 1893 1901 clcles perhaps due to intermittent vascular flow in 3rd n. nuc lear area 1929 Fuchs Axenfeld & Schlirenberg Greeves Behr Bielschowsky 1930 Selinger 1931 Petrovic & Ts chemolossow Bielschowsky Mak van Waal Bielschowsky Bonnet 1913 "'I924"" 1932 1932 1939 1941 cycles due to intermittentvascular stasis or to pressure of vessels clcles caused bl rhlthmic vasomotor changes in area of 3rd n. nucleus Eartial 3rd n . lesion due to insufficient blood SUJ2J21,l of eosterior nucleus cycles caused by changes in blood flow which influence the excitability of damaged nuclear c ells cycles due to storage of energy and rhythmic discharge of nuclear cells, under influence of blood SUJ2J2ll cycles due to intermittent angiospasms in area of oculomotor nucleus, caused b,l rhlthmic cortical activi!,y: (Eetit mal eguivalent) cycles due to fluctuations in blood supplv of 3rd nerve nucleus partial 3rd n . l esion mav be due to insufficient blooa sunnlv to nucleus clcles due to nv~ing vasomotor influences" lesion probably to congenital anomaly affecting 3rd n . nuclear vascularization, with cycles perhaps caused by (blood-borne) chemicnl stimuli ue some cases, and pointed to a basal rather than a midbrain lesion. Finally, the cyclic oculomotor spasms showed the very same pattern of innervation as was seen in the pathologic co-contractions of third nerve " misdirection synkinesia" (sec above), and some of the patients with the cyclic phenomenon had, in addition, frank "misdirection" signs: upon attempted up, down, or adduction movements the lid lifted, the pupil constricted, and accommodation increased, not only in the spastic but also in the paretic phases of the spontaneous cycles (Table 23-12). Thus, at least in these patients, a basal third nerve lesion did indeed exist. On the other side of the argument, many authors thought that partial impairment of the third nerve nucleus would make normal conduction of supranuclear impulses impossible. The eye therefore wou ld remain paretic until sufficient excitation had accumulated by summation of weak central stimuli, and then the remaining oculomotor neurons would discharge and a spasm would result. This process of summation of weak central impulses and intermittent discharges was much more likely to take place in the nucleus than in efferent third nerve fibers. Moreover, a nuclear site would also be compatible with the supernormal amplitude of the cyclic spasms, as well as with the influence of voluntary gaze efforts upon rate and extent of the cycles, and with the slowing of the cycles in sleep and their acceleration during arousal. These effects would be difficult to explain if the damage were located in the efferent third nerve fibers. As to the nature of the lesion, Rampoldi thought the defect to be due to some prenatal influence; and Bonnet assumed a genetic relationship because his patient had said that his mother had had the same kind of ocular palsy. But this idea was soon dismissed: besides Bonnet's and Petrovic and Tschemolossow's uncorroborated cases there was no familiar occurrence of this phenomenon. Most authors believed that the paresis must be due to aplasia or early impairment of the oculomotor nerve or nucleus. Trauma, infections, or an insufficient blood supply were thought responsible. The rhythmic spasms were thought to arise from summation of weak central impulses, as just described; or else the stimulation might be due to an irritative midbrain focus; or some central rhythm might stray to the oculomotor neurons, due to a pathologic process in the area. 2. Probable Site and Mechanism We believe that the arguments of both the " nuclear" and the "efferent" schools of thought are weighty and that, indeed, both theories are correct to a degree. The error was not in assuming a lesion at the base or in the midbrain , but in trying to limit the pathologic process to either site. In our opinion, this process must involve the third nerve, the oculomotor nucleus, and its central connections. These different kinds of injury are by no means mutually exclusive. To the contrary, when the probable pathologic sequence of events is considered, each step is likely to bring about the next with a high degree of probability. An injury to the third nerve fibers, caused at birth or in infancy by trauma or disease, affects the cells of origin of these fibers, and retrograde changes in many of the oculomotor neurons will result. Such secondary nuclear damage will necessarily have the distribution corresponding to impairment of a single efferent nerve, which would be baffling for any other disease process in the nucleus. Furthermore, when retrograde changes occur in the oculomotor neurons before their supranuclear connections have matured, many of the supranuclear fibers will fai l to establish proper synaptic contacts with these neurons; and consequently they will degenerate. 3 After the injury the surviving ocu lomotor neurons will recover, and regenerating nerve sprouts will grow from 23. Special Oculomotor Syndromes I Table 23-11. 1077 Assumed neural mechanisms for the origin of cyclic spasms YEAR AUTHOR MECHANISM 1900 1903 1906 Bechterew BielschowslSY Froma~et Salus 1913 1914 1914 1923 1924 1924 1931 1937 Lauber Zamorani v. Hi1212el Salus Behr Kubik Stein Hicks & Hosford Lowenstein & Givner 3rd n. [!als:y with irritation of variable intensi!,y - subthreshold in flaccid Ehase summation of suprrumclear im*ulses with intermittent discharges of nuclear cells irritation near partly aam~e oculomotor nucleus slowing of efferent impulses by 3rd n. scar, with intermittent ctiscnarges due to summation of subthreshold stimuli intermittent efferent discharges under the influence of supranuclear activity 3rd nerve nuclear discharges, interrupted by periods of exhaustion periodic spasms are triggered by supranuclear impulses, followed by relaxation rhythmic responses or damaged third nerve to central impulses "accumulation of energ,y 11 with rhithmic aischarges or surviving nuclear cells summation of subthreshold stimuli proximal to 3rd n. scar, with explosive discharges automatism of nuclear elements 1 de12rivea of su12ranuclear control summation of weak central stimuli by nuclear cells, with rhythmic discharges mr 1942 1945 McGregor 1949 Duke Elder 1963 Burian& Van Allen Crone & Horsten Morizane & Uemura Trounce & Clewett-Price 1970 1970 1973 1973 1973 Burde Hoyt barrage of constant, small supranuclear stimuli, with effect amplified by supersensitivity of nuclear cells, cut off from normal supranuclear- and reflex connections; flaccid phases due to long refractory intervals "storage" of subthreshold stimuli by nuclear cells, with periodic "ovenrnw" when ade9.uate intensi!,y is reached fatigue of partly destroyed nucleus, and irritation after recovery from fatigue, with normall;y subthresholcl stimuli acting by summation rhythmic discharges from "vegetative centers" may stimulate surviving cells of third nerve nucleus dischare:es from mesencephalic focus close to partially damaged 3rd n. nucleus alternate innervation and relaxation of near vision convergence, related to lowerigg of threshold bcfore 1 and raising after ciclic discharges spasms due to increased irritability of remnant elements or 3rd n. nucleus, which discharge after summation of weak subcortical stimuli; flaccid phases due to 12ost-discharge fati~e of these nuclear cells 3rd nerve lesion with "irritative focus feedigg into the infranuclear 12athwa:y 11 "active firing phenomenon ••• intermittent action potentials that fire from socalled unstable nerve membranes 11 their proximal axon stumps haphazardly across the scar, in the manner well known for basal third nerve lesions. In addition, some (collateral or other) sprouting of supranuclear fibers can be expected (sec Chapter 11 ). Depending on the nature and the severity of the primary damage the following results will be expected. First, in patients with total third nerve injury no normal oculomotor neurons will remain, and no physiologic movement will be possible. Second, in cases with less severe impairment, two cell populations must exist in the oculomotor nucleus: (a) normal neurons that escaped injury altogether or that recovered fully from slight damage, and (b) neurons that were hurt badly but survived. These recovered cells would have no normal connections, both centrally and peripherally, as just discussed. The cells of the first group will transmit residual physiologic movements, while those of the second group must be responsible for the abnormal cyclic spasms by a process of summation of subthreshold stimuli and of rhythmic mass discharges. Axons of a few 3. According to Hogg's embryologic findings (1968) the autonomic portion of the oculomotor nucleus is rather precocious in its development, but the supranuclear connecting fibers to them are very slow to form; and at birth a great many of them have not yet reached their destinations. healthy oculomotor neurons-which had been only nicked or bruised at the time of injury-may send fiber sprouts into peripheral channels of adjacent injured fibers, causing the slight but quick "misdirection" movements seen in some cases (see Figure 23-14 and Table 23-12). Such a mechanism would explain why the cyclic syndrome should have some features pointing strongly to an efferent lesion and others difficult to explain except by nuclear damage; why the amplitudes of residual normal eye movements and of pathologic spasms should be related inversely; and why the innervational pattern of the cyclic discharges should resemble so closely that of the "misdirection" syndrome which follows basal third nerve lesions in the adult. The difference between ordinary "misdirection dyskinesia" and the cyclic syndrome must be reJated to the time of injury. When the third nerve is damaged after mature supranuclear connections have been formed, volitional supranuclear and reflex impulses will be transmitted by normal synapses to the surviving oculomotor neurons, and central nervous regenerative sprouting is less likely to occur. The pathologic features in adult cases therefore are due mostly to ( l) the original paresis and (2) disorganized regeneration from proximal stumps of the damaged oculomotor nerve. In the cyclic syndrome, in contrast, many of the surviving oculomotor 1078 / IV. Pupillary Pathology: Symptomalogy Table 23-12. - Evidence for oculomotor misdirection dyskinesia CASE AUTIIOR FINDING #3 IH5 #28 Salzmann & Fuchs Salus Kubik ~ Bielschowsky Bielschowsky on attem2ted adduction lid went up, on abduction down, in either _ehase on attempted down-gaze globe rolled toward midline, in either phase lid moved up quickly and pup ii contracted on attempted adduction in either phase pseudo - von Graefe phenomenon on gaze down in eitEer pnase lid moved up quickly 3 mm and accommodation increased on attempted adduction in either phase; the reve rse happened on abduction convergence-, accommodation-, up- and down-gaze efforts caused momentary twitching of iris and lid during paretic phase lid did not cycle but lifted on attempted ad:duction in either pnase 2upil contracted on ad:duction and duated on a6duction in eitEer piiase lid retracted 2 mm on attempted adduction in either phase ~ #35 Selinge r ~ ~ #42 Stein Bielschowsky Hicks & Hosford neurons will be deprived of normal supranuclear input, in addition to their axonal defect; and this explains the queer mixture of reduced or abolished physiologic movements in the presence of extensive pathologic spasms of the same muscles. The origin of the rhythmic spasms could, we think, be understood on the basis of such a pathologic chain of events. Supranuclear firing to the third nerve nucleus never ceases. In the normal eye tonic impulses constantly reach the effector muscles, even when the eye rests in the primary position. Overt eye movements occur only when the outflow to a given muscle increases while that to its antagonist is inhibited. Therefore the pathologic oculomotor neurons with defective central synapses must be exposed to constant, weak stimulation: small quantities of mediator substance-perhaps from inappropriate collateral sprouts of fibers destined to other parts of the nuclear complex-must be present in the neighborhood of these cells, and must bring about increasing depolarization until the threshold of an explosive discharge is reached. And after a short refractory period, the slow process of depolarization will begin anew. This kind of summation of subthreshold stimuli with gradual depolarization and intermittent efferent volleys appears to be a more likely mechanism for the cyclic spasms than regularly repeated paralysis due to vascular or other causes or to straying of discharges from some other physiologic rhythm into the area of the oculomotor nucleus (see Table 23-11). For one, the ocular cycles are not merely an interrupted normal outflow: they are exaggerated in amplitude and abnormal in character. Even if one disregarded the many imperfections of the "vascular" theories, rhythmic changes in blood flow could not give rise to this kind of spasm. Second, the ocu lo motor spasms have no coincidence with any of the known autonomic rhythms such as the pulse or respiration, and they are too irregular even under steady conditions to make such a relation likely (see Figure 23-10). RA NUCLEAR NNECTIONS OCULOMOTOR NUCLEUS THIRD NERVE Figure 23-14. Diagram of assumed anatomic relations in patients with oculomotor paresis and spasms. Normal neurons are drawn plump, with healthy dendrites, and surviving injured neurons are shown flabby, with drooping dendrites. These features were drawn for easy recognition and are not thought to represent the true anatomic appearance of these cells. Supranuclear nerve endings synapse normally with healthy motor cells but not with the abnormal neurons. At the site of the third nerve scar diffusely regenerated nerve sprouts from injured axons join fiber bundles to the different effectors. A few normal axons that were only nicked or stretched at the time of injury may send sprouts to neighboring injured channels (sec middle neuron). (From I.E. Loewcnfeld and H.S. Thompson, Survey Ophthal. , 20 [1975]:81) y '' ''I '' ' I' '' I : ,,,' Ciliary ganglion Extraocular muscles Upper lid EFFECTORS 23. Special Oculomotor Syndromes The assumption of intermittent discharges from some nearby irritative focus is not an explanation: it merely says that the spasms are thought to be pathologic, but does not explain their cyclic nature. Crone and Horsten (1970) observed intermittent EEG discharges, time-related to the ocular cycles. But it should be noted that in their case the spastic movements preceded the volleys of cortical activity, and sometimes they occurred without EEG changes. This prompted Crone and Horsten to think that the irritative focus was likely to be situated in the midbrain, and the impulses therefore would reach the oculomotor nucleus more quickly than the cortex. The muscle spasms require, however, that the excitation be transmitted to the eye, which transmission should take at least as long as conduction to the cortex, and further time must be consumed by the latent period of the effectors. We therefore suggest that the activity arose from the oculomtor nucleus itself, that is, that discharge of the oculomotor neurons was the primary event and that, in this case, action potentials strayed to the cortex via some afferent connection. As mentioned above, a number of authors have already thought of a process of summation of supranuclear activity with repeated discharges (Table 23-11). While we agree with this, we believe that the paretic phases should not be ascribed to refractoriness, "fatigue," or " exhaustion" of the oculomotor cells. It is hard to imagine life continuing with central neurons refractory for minutes at a time, or the cells themselves surviving if they were victims of such repeated, prolonged periods of exhaustion between bursts of maximal activity. That the oculomotor neurons indeed are not refractory during the flaccid phase of the cycles is proven by those experiments in which attempted adduction of the affected eye can interrupt the paralytic phase and maintain the spasm as long as the adduction effort is continued. As discussed in detail in the 1975 paper, our assumptions about the pathologic process would allow us to trace the origin of the cyclic oculomotor syndrome to a 4. Kommerell and co-workers recently (1985; 1988) have furnished just such evidence in detailed examinations of two patients. Electromyographic and electron-miscoscopic studies revealed the presence of peripheral neuronal impairment with secondary myopathy, and with evidence of still-ongoing axonal atrophy and regeneration. Based on their findings and on interesting discussions of related findings in the facial and abducens nuclei after damage to their respective motor nerves (Blinzinger and Kreuzberg, 1968; Delgado-Garcia et al., 1988), the authors suggested that chronic rather that acute impairment of the oculomotor nerve caused the cyclic syndrome. If this were indeed the case, the relative rarity of cyclic compared to paretic cases of congenital oculomotor deficit would be explained. / 1079 single lesion, and all the different aspects of the condition would fall neatly into place. In contrast, it is impossible to account for all these features by a primary brainstem lesion, or by damage limited to the efferent third nerve fibers. However, our explanation is a hypothesis, and direct proof of a combined efferent and nuclear-supranuclear defect must await future work. Aside from anatomic proof, we think that electromyographic records of the extraocular muscles-in patients old enough to allow such tests to be done without narcosis-would be most useful,4 since they would show whether there is indeed co-contraction of the superior and inferior recti during the spasms, causing the remarkable absence of vertical spastic movements. In a case of atypical cyclic oculomotor palsy, published by Hyams, Sharf, and Neumann (1973), there was severe brain damage due to birth trauma, and electromyographic studies of the medial rectus muscle on the side of the third nerve involvement revealed a lower motor neuron defect. However, because the child was mentally retarded and uncooperative, the test had to be done in anesthesia, and the cycles ceased. Therefore, no information was obtained about the action currents to the eye muscles during the active phase of the cycles. Before publication of our results in 1975 these cases generally were considered extremely rare. However, the full-blown cyclic syndrome sometimes was not recognized for years by the examining physicians, and occasionally was not even noticed by the patient's parents. It therefore appeared probable that in patients with congenital third nerve palsy cyclic activity might be found more often than it has been in the past if it were looked for carefully. This thought was proven correct by Fells and Collins (1979): when they began to observe meticulously all patients who came to their clinic with congenital third nerve palsy, they found nine cases with cyclic features within 4 years. Similarly, Miller (1977), who assembled thirty cases of isolated third nerve palsy in children from the Johns Hopkins Hospital records, found three children with congenital onset to have developed the cyclic syndrome.