Journal of Neuro-Ophthalmology, March 1992, Volume 12, Issue 1

Evolution of oculomotor nerve palsies.

The management of patients with isolated oculomotor nerve palsies (OMPs) who have normal pupils and no other signs of neurological disease is a controversial issue. A more precise delineation of the clinical course of isolated OMPs may help to determine whether neuroradiologic evaluation is indicated in these cases. We studied 41 patients with isolated third cranial nerve palsies, emphasizing the times of progression and resolution of the oculomotor nerve dysfunction. The average interval from onset to development of maximal ophthalmoplegia failed to differentiate between a microvascular etiology (3.3 days) or posterior communicating artery aneurysm (3 days). Of the 28 patients with diabetic or idiopathic palsies, regardless of pupillary involvement, 68% had improvement of the oculomotor paresis within 4 weeks, 96% within 8 weeks, and 100% within 12 weeks of the onset of symptoms. Our study suggests that patients with pupil-sparing OMPs should be considered for extensive neuroradiologic evaluation only if there is deterioration or failure to improve within 4 to 8 weeks.

Journal of Cli" ical Neuro- ophthalmology 12( 1), 21- 25, 1992, Evolution of Oculomotor Nerve Palsies Hilda Capo, M. D., Floyd Warren, M. D., and Mark J. Kupersmith, M. D. I[) 1992 Raven Press, Ltd" New York The management of patients with isolated oculomotor nerve palsies ( OMPs) who have normal pupils and no other signs of neurological disease is a controversial is­sue. A more precise delineation of the clinical course of isolated OMPs may help to determine whether neurora­diologic evaluation is indicated in these cases, We stud­ied 41 patients with isolated third cranial nerve palsies, emphasizing the times of progression and resolution of the oculomotor nerve dysfunction. The average interval from onset to development of maximal ophthalmoplegia failed to differentiate between a microvascular etiology ( 3.3 days) or posterior communicating artery aneurysm ( 3 days). Of the 28 patients with diabetic or idiopathic palsies, regardless of pupillary involvement, 68% had improvement of the oculomotor paresis within 4 weeks, 96% within 8 weeks, and 100% within 12 weeks of the onset of symptoms, Our study suggests that patients with pupil- sparing OMPs should be considered for ex­tensive neuroradiologic evaluation only if there is dete­rioration or failure to improve within 4 to 8 weeks. Key Words: Intracranial aneurysm- Oculomotor palsy- Third cranial nerve, From the Bascom Palmer Eye Institute ( H, C) University of Miami, Miami Florida, and the Departments of Ophthalmology ( F. W" M.], K.) and Neurology ( M,]. K.) New York University Medical Center, New York, New York, U, S, A, This work was supported in part by an unrestricted grant from Research to Prevent Blindness to the Department of Oph-thalmology, New York University. . This paper was presented at the 42nd Annual Meehn, g of the American Academy of Neurology, May 3, 1990, Miami Beach, Florida. Address correspondence and reprint requests to Dr. Hilda Capo, 900 N. W. 17th Street, Miami, FL 33136, U. S. A, 21 The management of patients with isolated third cranial nerve palsies is a controversial issue. It is generally accepted that computed tomography ( CT) or magnetic resonance imaging ( MRI), fol­lowed by cerebral angiography, should be per­formed to rule out the presence of an aneurysm in patients with oculomotor nerve palsy ( OMP) and pupillary paresis, but the proper approach in cases with pupillary sparing is unclear. An isolated, pu­pil- sparing OMP usually occurs with microvascu­lar infarction of the nerve ( 1,2); there is general agreement that a normal pupil practically excludes an aneurysm as the cause of the OMP ( 2,3). Kissel ( 4), however, reported four patients with a poste­rior communicating artery ( PCoA) aneurysm who presented with pupil- sparing OMP and no signs of subarachnoid hemorrhage ( SAH). Progression to pupillary involvement occurred in three of the pa­tients ( 4). Recently, complete external ophthal­moplegia with pupillary sparing was reported in a patient with a basilar artery aneurysm ( 5). The oc­currence of pupil- sparing OMPs with intracranial aneurysms has led some authors to recommend neuroimaging studies ( 5) and many neurosur­geons to perform cerebral angiography ( 6) in all patients with OMP regardless of the state of the pupil. A more precise definition of the time course of evolution of acute, isolated OMPs may be useful in determining the need for neuroradiographic stud­ies in these cases. We studied 41 cases of isolated third cranial nerve palsy, with special attention to the course of progression and resolution of the oc­ulomotor nerve dysfunction. SUBJECTS AND METHODS We reviewed the medical records of patients evaluated between 1982 and 1989 by the New York University Medical Center Neuro- Ophthalmology Service for acute isolated third nerve palsies. Only 22 H. CAP6 ET AL. patients with adequate history and follow- up were included. In order to assess only patients wtth an isolated OMP, patients with additional cranial neuropathies or systemic or neurologic symptoms at presentation were not included. Traumatic cases and those with evidence of SAH were also ex­cluded. Particular attention was given to the pu­pillary status, presence of pain, the degree of in­volvement of the extraocular muscles ( EOM), and the time course of evolution of the OMP. Patients were grouped according to the degree of pupillary and EOM involvement ( Table 1). Par­tial pupillary dysfunction was defined as ipsilateral pupil dilation of more than 1 mm or decreased reactivity in cases of equal pupillary size. External ophthalmoplegia was considered partial when the appropriate muscles were underacting but not fully paralyzed, or when some of the appropriate muscles were spared. Cases were classified according to the etiology of the third nerve palsy. Idiopathic and diabetic pal­sies were grouped together on the presumption that both share an ischemic microvascular etiology and a benign course. Cases of intracavernous in­ternal carotid artery ( lCA) aneurysms and menin­giomas of the cavernous sinus region were com­bined as compressive lesions of the cranial nerves in the cavernous sinus. All patients with pupillary involvement, except one, underwent CT or MRI and cerebral angiography to confirm that there was no intracranial aneurysm. RESULTS Forty- one patients met our criteria for inclusion. Twenty- eight of them ( 6690) had an idiopathic or diabetic ( presumed microvascular) etiology, and 10 patients ( 26%) had angiogram- proven aneurysms ( 7 PCoA, 3 cavernous ICA). Two patients ( 5S7c) had a meningioma in the cavernous sinus area, and one ( 3%) had CNS lymphoma. TABLE 1. Degree of oculomotor nerve inVOlvement Idiopathic or Diabetic Etiology The group with idiopathic or diabetic etiologies included 12 women ( 43%) and 16 men ( 57%), with an average age of 67 years ( range 2~ 89 years). Five patients had diabetes mellitus, 7 had high blood pressure, and 2 had both diseases ( T~ ble. 2). The 14 patients without any known systemIC dIsease had a negative 4- or 5- hour glucose tolerance test. The pupil was spared in 21 patients ( 75%). and involved in 7 ( 2590). Two of the seven patIents with pupillary involvement initially presented with pupillary sparing, but developed pupil pare­sis at days 11 and 14. Of those with pupillary in­volvement, three had complete iridoplegia and four had partial pupillary dysfunction; EOM dys­function was complete in four patients and partial in three ( Table 1). Six of the patients with pupillary involvement had a normal head CT or MRI and a normal cerebral angiogram of the ipsilateral ICA and vertebrobasilar artery, which confirmed the absence of an aneurysm, The only patient who re­fused cerebral angiography had a normal MRI and spontaneous improvement of the paresis. Of the 21 patients with pupillary sparing, 17 had partial and 4 had complete external ophthalmople­gia ( Table 1), In two of these patients, only the superior division was involved. Because third nerve ischemia rarely spares the inferior division, these patients had a head and orbit CT or MRI, the results of which were normal. Ipsilateral periorbital or retroorbital pain was present in 16 patients ( 610/ c) with a microvascular etiology, The pain preceded the onset of ophthal­moplegia in seven patients, was concurrent in eight, and appeared afterwards in two. The time from the first symptoms to the devel­opment of maximal internal and external ophthal­moplegia is shown in Fig. 1. The mean time of progression was 3.3 days ( SO ± 3.2). The improve­ment rate is shown in Fig. 2. Sixty- eight percent of the patients had improvement of the OMP within 4 weeks; 96S7c, within 8 weeks; and 100%, within 12 weeks of the onset of symptoms. CNS. central nervous system: NP. normal pupil; PP. partial pupil dysfunction: CP, complete pupil dysfunction: PO, partial external ophthalmoplegia: CO complete external ophthalmoplegia NP. PO NP. CO PP. PO PP. co CPo PO CP, CO Total Diabetic or idiopathic 17( 61%) 4 ( 14%) 2 ( 7%) 2 ( 7%) 2 ( 7%) 1 ( 4%) 28 ( 100%) Posterior communicating aneurysm oo2 ( 29%) , ( 14%) 1 ( 14%) 3 ( 43%) 7 ( 100%) Cavernous sinus lesion 2( 40%) o2 ( 40%) o o1 ( 20%) 5( 100%) eNS lymphoma o o1o o o TABLE 2. Distribution by etiology Diabetic Posterior Cavernous or communicating sinus CNS idiopathic aneurysm lesion lymphoma Total cases 28 7 5 1 Average age 67 years 57 years 58 years 56 years Women 12 ( 43%) 5 ( 71%) 3( 60%) 0 Men 16 ( 57%) 2 ( 29%) 2 ( 40%) 1 Pain 17 ( 61%) 5 ( 71%) 3 ( 60%) 0 OM 5( 18%) 0 0 1 HBP 7 ( 25%) 2 0 0 OM and HBP 2( 7%) 0 0 0 OM, diabetes mellitus; HBP. high blood pressure. OCULOMOTOR PALSIES 23 FIG. 1. Interval from first symptoms of oculomotor nerve palsy to maximal ophthalmoplegia. Posterior Communicating Artery Aneurysms Seven patients ( 18%), all with pupillary dysfunc­tion at presentation, had angiogram- proven PCoA aneurysms ipsilateral to the OMP. There were five women and two men, with a mean age of 57 years ( range 37- 68 years). Two of the patients had high blood pressure, and none had diabetes mellitus ( Table 2). Pain was present in five patients ( 71 %) and preceded the onset of ophthalmoplegia in four. Pupil dysfunction was complete in four pa­tients and partial in three. The external ophthal­moplegia was complete in four patients and partial in three ( Table 1). The course of progression is shown in Fig. 1. The difference in the mean time of progression be­tween the microvascular ( 3.3 days) and the PCoA ( 3 days, SO ::!:: 2.7) OMPs was not statistically sig­nificant by the Mann- Whitney test. NUMBER OF CASES 25 1 21 20 j 15 ~ Lymphoma One patient who initially presented with a par­tial internal and external OMP worsened over 1 month and developed paresis of the ipsilateral fourth and sixth cranial nerves. Magnetic reso­nance imaging and cerebral angiography per­formed at the time of presentation were normal, but the glucose tolerance test demonstrated a dia­betic curve. A lumbar puncture, performed at 1 month, revealed lymphoma cells in the spinal fluid. A systemic evaluation did not show lym­phoma outside of the central nervous system. DISCUSSION men ( 55 and 70 years old). Three patients had periorbital pain ipsilateral to the lesion ( two ICA aneurysms, one meningioma). The external oph­thalmoplegia was partial in four and complete in one patient; three patients had internal ophthal­moplegia ( Table 1). The two patients with pupil­lary sparing ( one meningioma, one ICA aneurysm) had no improvement of the OMP by eight and nine weeks, when neuroradiologic studies were performed. The time course of progression was variable, ranging from 1 day to 3 years. One pa­tient with a cavernous ICA aneurysm had sponta­neous thrombosis of the aneurysm, with improve­ment of the pupil- involving OMP within 1 month and complete resolution within 4 months. o 13- 15 ro •• o 10- 12 4 [- I . 0 c ---' 4- 6 2 .,,:=::~ [. 7- 9 TIME (~ YS) o mlcronIScular _ post comm lUIelllY5m 5 1- 3 o 10 j 5~ Cavernous Sinus Lesions Three patients ( 8%) had angiogram- proven an­eurysms of the intracavernous portion of the ICA, and two ( 7%) had a meningioma in the cavernous sinus area. Both conditions were grouped together as compressive lesions of the cranial nerves in the cavernous sinus. The three patients with intracav­ernous ICA aneurysms were women ( 25, 67, and 74 years old), and the two with meningiomas were The recommendations for the evaluation of pa­tients with a nontraumatic, isolated third cranial nerve palsy usually vary according to the degree of pupillary and EOM involvement. The question is: To what extent is a third nerve paresis a harbinger of a life- threatening condition, such as an intracra­nial aneurysm? lntracavernous ICA aneurysms can occasionally cause an isolated OMP, but these differ from the PCoA and basilar artery aneurysms in that they carry only a minimal risk of producing a significant neurological deficit or death. Rupture of intracav­ernous ICA aneurysms usually results in a carotid­cavernous fistula without causing SAH. Only two cases of SAH caused by a ruptured intracavernous aneurysm have been reported ( 7,8). Consequently, emergency treatment in most cavernous carotid aneurysms is not recommended. Approximately 86- 100% of patients with OMPs caused by intradural aneurysms will have some degree of pupillary dysfunction at presentation ( 2,4,9- 11) making it necessary to exclude an aneu­rysm in cases where the pupil is involved. It is week 2 week 12 '! II OF CASF. S IMPROVED 96 1:: 68 r-'--~ ~+--",,"",_ 2~ 5~. L---. r r- t--,---~ week 4 week 8 TIME INTERVAL ( WEEKS) FIG. 2. Improvement rate of microvascular oculomo­tor nerve palsy. , CLi" Neuro- ophthalmol. Vol. 12, No. 1, 1992 24 H. CAPO ET AL. generally agreed that, because of the risk of a SAH from rupture of PCoA or basilar artery aneurysms, patients with partial or complete iridoplegia, irre­spective of the degree of external ophthalmople­gia, should have neuroimaging studies including cerebral angiography for patients older than 20 years of age. If the results of these studies are nor­mal, a lumbar puncture should be performed to rule out a low- grade meningitis or lymphoma. Patients with complete external ophthalmople­gia and sparing of the pupil are most likely to have suffered an ischemic event ( 3). A microvascular in­farct of the extra- axial portion of the nerve with sparing of the peripheral pupilloconstrictor fibers has been identified in pathology specimens from diabetic OMPs, which explains the preservation of the pupillary function ( 12- 14). Therefore, cerebral angiography is usually not initially recommended when the pupil is spared and the patient is 50 years of age or older and without SAH ( 3). Re­cently, Lustbader and Miller ( 5) reported a com­plete external oph thalmoplegia with pupillary sparing in a patient with a basilar artery aneurysm. This is the only case in the literature of an intra­cranial aneurysm with this presentation. The clin­ical course of this patient differed from that of our patients with microvascular disease in that there was no improvement 8 weeks after the onset of symptoms, while 969< of our patients had already improved by this time. We agree with previous recommendations ( 15) that patients with complete external third nerve palsies and sparing of the pu­pil do not require neuroradiologic studies except when the patient either deviates from the usual clinical course of an ischemic OMP or in younger patients in whom an ischemic process is therefore unlikely. Trobe ( 3) recommends cerebral angiography for adults with an incomplete OMP and a normal pu­pil, particularly if the inferior division is spared. Although diabetic isolated palsies of the superior division of the third cranial nerve have been re­ported ( 16), these palsies are most commonly caused by compressive lesions, such as neoplasms and aneurysms of the ICA in the anterior cavern­ous sinus, where the nerve bifurcates ( 17) or less frequently, by basilar artery aneurysms ( 17,18). In patients with a superior division paresis of the oc­ulomotor nerve, a high- resolution contrast CT scan or MRI is usually adequate to visualize the cavern­ous sinus and basilar artery areas and should be initially obtained in these patients ( 17). There are very few cases in the literature of PCoA aneurysms causing incomplete OMPs with a normal pupil. Kassof et ,11 ( 19) and Oono et al. ( 20) have each reported one case of a PCoA aneurysm with a pupil- sparing partial third nerve palsy. Bar­tleson et al. ( 21) reported three patients who pre­sented with an incomplete pupil- sparing OMP caused by unruptured intracranial aneurysms, one in the basilar artery and two in the ICA ( presum­ably PCoA junction). None of these patients had improved 6 weeks after the onset of symptoms. Kissel et al. ( 4) reported four patients with PCoA aneurysms without SAH, who presented initially with pupil- sparing partial OMPs. However, one had an ipsilateral abducens palsy; two developed a complete iridoplegia within 5 days; and one, by 4 months. Pupil- sparing, partial OMP appears to be a rare presentation of intracranial aneurysms, but is common in idiopathic or diabetic OMP as ob­served in 61 ( 7c of our patients with microvascular etiology ( Table 1). Since most of the patients with intracranial an­eurysms initially have an abnormal pupiL or will develop pupillary involvement within several days of the ophthalmoparesis ( 4,6), and 68% of the pa­tients with idiopathic or diabetic OMPs will im­prove by 1 month and 969< by 2 months, it seems prudent to closely observe the patient with a pu­pillary- sparing third nerve paresis for 4 to 8 weeks before performing neuroradiographic studies, par­ticularly cerebral angiography. Previous reports suggest that a CT scan MRI scan should be per­formed earlier in adults younger than 50 years of age and in those with an isolated superior branch paresis. It may be argued that 4 weeks is a long period of time, since Okawara ( 22) found that in cases of PCoA aneurysms the EOM involvement preceded the rupture of the aneurysm by an av­erage of 29.6 days. It should be noted, however, that this average was based on onlv 6 cases, and no information was provided on the ' pupillary status, so this information may not apply to cases of pu­pil- sparing OMP. It is unfortunate that the time of progression of the third nerve paresis is not helpful in distin­guishing patients with an ischemic etiology from those with an aneurysm. We found that both groups worsened over an average of approxi­mately 3 days. In conclusion, patients with OMPs that involve the pupil ( either initially or later) should have ex­pedited noninvasive neuroimaging studies and ce­rebral angiography at the time of presentation. In patients with isolated complete or partial external ophthalmoplegia and normal pupils, the clinical course remains helpful in determining the extent of the neuroradiologic evaluation. Though one could argue that the miniscule risk of MR or CT OCULOMOTOR PALSIES 25 warrants that all patients be studied, our data sug­gests that only patients who fail to improve within 4 to 8 weeks must be scanned. According to pre­vious reports, exceptions include patients with a superior division paresis in whom compressive le­sions are common, and younger patients in whom an ischemic process is unlikely. REFERENCES 1 Nadeau SE. Trobe JD Pupil sparing in lKulomotor palsv: a brid re\' lew. AI111 Nellr,) 1 19i13; 13: I- IJ-- ll. ~ RULker CW The causes llf p, uail'si,; l'f the third. fourth and shth Lranial ner\' es. Alii Ill/' ilt/ IIl! IIII)! I% b; bl : 12Y3- il. 3. Trl) be JD. Isolated pupil- sparin~ third nerve palsv Uphtha! ­IIWlt',\ I/ 1985; 9258-- b1 - I. K. iss~ i. fT, Burde RM. Klin~ ele TG. Zei~ er NE. Pupil- sparin~ oLulomotor paresis with internal Larotid- posterior Lommu­nicating artery aneurysms. AIII1 NellroI1983; 13: 149- 54. ~. Lustbader JI\ I, Miller NR. Painless. pupil- sparing but oth­erwise complete oculomeltor ner\' e paresis caused by basi­lar arterY aneurYsm. Areh OpIJlha/ I1/('/ 1988; 106: 583-- l. 6. O'Conn~ lr PS. Tredici T). Green RP. Pupil- sparing third nerve palsies caused by an aneurysm. Alii I Ophtha/ lllol 1983; 95: 395-- 7. 7. Barr HWK. BlaLkwood W, Meadows SP. lntracavernous carotid aneurysms: a clinical- pathologic report. Bralll 1971; 94: 607- 22. 8. Hodes JE. Fletcher WA. Goodman DF, Hoyt WF. Rupture of ca\' ernous carotid aneurysm causing subdural he­matoma and death: case report. I N~ llYllSllrs 1988; 69: 617- 9. 9. Rucker CWo Paralvsis of the third. fourth. and sixth cranial nerves. Am I ophi/ Ill/ mol 1958; 46: 787- 94. 10. Green WR. Hackett ER. Schlezinger NS. Neuroophthal-moillgic evaluation of oculomotor nerve paralysis. Arch Uphtllll/ lllo' 1% 4; 72: 154-- 67. 11. Keane JR. Aneurysms and third nerve palsies. A11Il Nellral 1983; 14: 69h-- 7 12. Dreyfus PM. Hakim S. Adams R. Diabetic ophthalmople­gia: report llf caSe' with postmortem study and comments eln vascular supply of human oculomotor nerve. AMA Arch Nellrol Psych 1957; 77: 337- 49. n. Asbury AK. Aldredge H, Hershberg R. Miller- Fischer C. Oculomotor palsy in diabl'les mellitus: a c1inico- patho­logical study. Bralll 1970; 93: 555- 66. 14. Daroif RB. DIscussion of diabetic ophthalmoplegia: a dinico- pathologic investigation. TrailS Alii Nellrol Ass 1969; 94: 6h-- 8. 15. Trobe JD. Third nerve palsy and the pupil: footnotes to the rule Arcil Upiltllll/ mo! 1988; 106: 601- 2. 16. Masucci EF. Kurtzkt' JF Diabetic superior branch of the oculomotor nerve. AIIII Nellro! 1980; 7: 493. 17. Guy). Savino PI. Schatz N). Cobbs WH, Dav AL. Superior division paresIs of the oculomotor nerve. Ophthalmology 1985; 92: 777-- 84. 18 Trobe ID. Glaser JS. Quencer RC. Isolated oculomotor pa­ralvsis: the product of saccular and fusiform aneurysms of the basilar artery. Arch Ophtha/ lllol 1978; 96: 1236- 40. 19. Kasoii I. Kelly DL. Pupillary sparing in oculomotor palsy from internal carotid aneurysm. I Nt" lra," rs 1975; 42: 713- 7. 20. Oon" S. Shinohara Y. Fujii K. Pupillary sparing in oculo­motor pals)' from internal carotid aneurysm: case report. Highlights ill Nellro- ophthallllolugy. Pn1ceedi, lgs of the Sixth MedillS of the IlItentallO/ 1ll1 1 ellro- ophthallllology SOCIety. Ha­kone, Japan. 1986203-- 8. 21. Bartleson JD. Trautman Je. Sundt TM. Minimal oculomotor nerve paresis secondary to unruptured intracranial aneu­rysm. Arch NClIroI1986; 43: 1015-- 20. 22. Okawara S. Warning signs prior to rupture of an intracra­nial aneurysm. I Nellroslirg 1973; 38: 575-- 80. I C/ 1I1 N~ l1rO-[ 1plltiUllmo/' Vat. 12, No. 1. 1992