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Show Journal of Neuro- Ophthaliuology 15( 3): 136- 141, 1995. © 1995 Lippincott- Raven Publishers, Philadelphia Relative Pupillary Sparing Third Nerve Palsies To Arteriogram or Not? Mary Ellen Cullom, M. D., Peter J. Savino, M. D., Robert C. Sergott, M. D., and Thomas M. Bosley, M. D. Ten consecutive patients with acute relative pupillary sparing third nerve palsies were enrolled in a prospective study to determine the prevalence of intracranial aneurysm. All patients were imaged with either cerebral angiography or magnetic resonance angiography. None of the patients demonstrated an intracranial aneurysm. The prevalence of aneurysm in patients with relative pupillary sparing third nerve palsies may be low enough to preclude the use of routine angiography in this condition. Key Words: Third nerve palsy- Pupil- Arteriogram- Aneurysm. The " rule of the pupil" has dictated the approach to third nerve palsies in neuro- ophthalmic practice for years. The rule states that when an aneurysm is the cause of a third nerve palsy, the pupil will be dilated and sluggish. Conversely, if the pupillary size and response is normal, aneurysm is unlikely to be the cause of the palsy ( 1). Therefore, the appropriate management of third nerve palsies is: if the pupil is involved presume there is an aneurysm, perform an MRI or CT scan to exclude a mass, and if no mass, then perform an arteriogram. If the pupil is spared, presume aneurysm is not the cause and proceed with an evaluation for vasculopathic risk factors. In cases of relative pupillary sparing ( i. e., when the pupil is only partially involved in a complete external ophthalmoplegia or when the involvement of the extraocular muscles is much greater than the degree of pupillary involvement), the appropriate management is not clearly defined. We conducted a prospective investigation of ten patients with relative pupillary sparing third nerve palsies to try to better define this issue. Manuscript received June 30, 1994. From the Department of Ophthalmology ( M. E. C.), Eastern Virginia Medical School, Norfolk, Virginia; and Neurophthalmology Service ( P. J. S., R. C. S., T. M. B.), Wills Eye Hospital, Philadelphia, Pennsylvania, U. S. A. Address for correspondence and reprints requests to Dr. Peter ]. Savino, Neuro- ophthalmology Service, Wills Eye Hospital, 900 Walnut St., Philadelphia, PA 19107, U. S. A. MATERIALS AND METHODS Ten consecutive patients with relative pupillary sparing third nerve palsies were seen in consultation at the Wills Eye Hospital Neuro- ophthalmology Service. Evaluation of each patient included Snellen visual acuity, confrontation visual fields, extraocular motility, pupil size and reactivity, slit- lamp biomicroscopy, and fundus examination. Specifically, pupil size and reactivity was confirmed by one of the senior neuro- ophthalmic staff ( P. J. S., R. C. S., T. M. B.). After the diagnosis of an isolated relative pupillary sparing third nerve palsy was made, the patients were imaged by either CT or MRI scan to exclude an intracranial 136 THIRD NERVE PAES1ES 137 mass. Nine patients then underwent cerebral arteriography, and one patient underwent magnetic resonance angiography ( MRA) because she was not systemically well enough to be subjected to cerebral arteriography. MRA, with high spatial resolution, is thought to be sensitive to aneurysms which are larger than 3 mm in diameter ( 2,3). In no case did a patient have an evolving third nerve palsy after initial presentation. Eight patients were male and two female. The age range of the patients was 52- 77 years of age; the mean age was 66 years. Eight of ten patients were hypertensive and four of ten had diabetes mellitus. Eight of the palsies were left- sided and two right- sided. Eight of the ten patients experienced either a dull ache around the affected eye or a headache on the affected side ( Table 1). CASE REPORTS Case 2 A 67- year- old woman with hypertension, angina, asthma, and diverticulitis presented with a three- week history of left frontoparietal headache and an eight- day history of left- sided ptosis. Best corrected visual acuity was 6/ 9 in each eye. Visual fields were full to confrontation. There was complete ptosis on the left. Extraocular motility was full in the right eye. Motility in the left eye showed full abduction, 0% adduction, 30% elevation, and depression ( Fig. 1). The right pupil was 3 mm in room light and constricted briskly to 2 mm with bright light. The left pupil was 5 mm in room light and constricted sluggishly to 3 mm with bright light. Slit- lamp biomicroscopy and fundus examination were normal. An MRI showed small- vessel ischemic change. A cerebral arteriogram of the right and left internal carotid arteries and left vertebral artery was normal. The patient was last seen two months after initial presentation, only 1 mm of left- sided ptosis remained, extraocular motility was full in both eyes, pupil size was 3 mm OD and 4 mm OS, and there were no signs of aberrant regeneration. Case 3 A 69- year- old woman with hypertension, diabetes mellitus, and hypothyroidism presented with binocular diplopia, left ptosis, and a dull ache OS for two weeks. Best corrected visual acuity was 6/ 9 in each eye. Visual fields were full to confrontation. There was 2 mm of left- sided ptosis. Extraocular motility was full in the right eye. Motility in the left eye showed full abduction, 30% adduction, 70% elevation, and 60% depression. The right pupil was 3.5 mm and constricted briskly with bright light. The left pupil was 4.5 mm and reacted sluggishly to bright light. Slit lamp biomicroscopy and fundus examination were normal. An MRI was normal. An MRA was performed which showed no evidence of aneurysm. The patient was seen three months after initial presentation, the left ptosis had resolved, extraocular motility was full in both eyes, pupil size was 3.0 mm OD and 4.0 mm OS, and there were no signs of aberrant regeneration. Case 7 A 52- year- old man with hypertension and diabetes presented with left- sided headache, left ptosis, and diplopia for one week. Best corrected visual acuity was 6/ 12 in the right eye and 6/ 21 in the left eye. Visual fields were full to confrontation. There was 75% ptosis of the left upper lid. Extraocular motility was full in the right eye. Motility in the left eye showed full abduction, 5% adduction, 15% elevation, and 15% depression. The right pupil was 5 mm in room light and constricted briskly to 3 mm with bright light. The left pupil was 7 mm in room light and constricted sluggishly to 5 mm with bright light. Slit- lamp biomicroscopy was normal. Fundoscopic examination revealed background diabetic retinopathy in both eyes and panretinal photocoagulation scars in the periphery of the left fundus. A CT scan was normal. A left internal carotid arteriogram was performed and failed to demonstrate an aneurysm. The patient was last seen four years after initial presentation, the left- sided ptosis had completely resolved, extraocular motility was full in the left eye, pupillary size was 4 mm OU, and there were no signs of aberrant regeneration. DISCUSSION Evidence to support the " rule of the pupil" is abundant in the literature. In a series by Green et al. ( 3), 36/ 38 patients with third nerve palsies secondary to cerebral aneurysms had pupillary involvement. Rucker ( 4) reported sphincter impairment in 62/ 64 cases of aneurysm. Despite these series that have provided the foundation for the rule of the pupil, there are numerous reports of patients who have not obeyed the rule. Patients have presented with pupillary sparing third nerve palsies and were found to have internal carotid, posterior communicating, and basilar artery aneu- / Neuro- OpMhalmol, Vol. 15, No. 3, 1995 138 M. E. CULLOM ET AL. TABLE 1. Patient characteristics3 Pt./ age ( yr)/ sex 1/ 64/ M 2/ 67/ F 3/ 69/ F 4/ 65/ M 5/ 62/ M 6/ 67/ M 7/ 52/ M 8/ 73/ M 9/ 61/ M 10/ 77/ M Pt./ age ( yr)/ sex 1/ 64/ M 2/ 67/ F 3/ 69/ F 4/ 65/ M 5/ 62/ M 6/ 67/ M 7/ 52/ M 8/ 73/ M 9/ 61/ M 10/ 77/ M Medical history Eye Hypertension Hypertension, OD" OS coronary artery OD disease mitral val prolapse, asthma Hypertension, ve OS" diabetes OD mellitus, hypothyi Hypertension Hypertension, roid OS" OD OS" diabetes OD" mellitus, tubercul ulcer disease Hypertension, mellitus, go Hypertension, osis, peptic OS diabetes OD ut OS" diabetes OD mellitus, arthritis Dysplastic nevi None Hypertension, mellitus Lids OS" OD OS" OD OS" diabetes OD Complete ptosis Normal Normal Complete ptosis Normal 2- mm ptosis Normal Complete ptosis Moderate ptosis Normal Normal 4- mm ptosis Normal 75% ptosis Normal Complete ptosis Normal 2- mm ptosis Normal 4- mm ptosis OS" Motility 0% add, 20% elev, 100% abd Full Full 0% add, 30% elev, 100% abd Full 30% add, 70% elev, 100% abd Full Ocular history Visual acuity Ptosis OD, diplopia x l day Left sided headache x3 weeks Ptosis OS Dull ache Ptosis OS, x8 days OS x2 weeks diplopia x2 weeks Ache OS x2 weeks Ptosis OS, diplopia x2 weeks Pain OD, ptosis OD, diplopia x5 days Pain OS, cli plopia x l week Left sided headache, ptosis OS, dipl Dull ache diplopia Ptosis OS, Dull ache opia x l week OS, ptosis OS, x1 week diplopia x2 days OS, diplopia x 10 days 0% dep, 30% dep, 30% dep, 0% add, 0% elev, 20% dep, 100% abd 10% add, 40% elev. 100% abd Full Full 20% add, 20% elev, 100% abd Full 50% add, 15% elev. 100% abd Full 0% add, 10% elev, 100% abd Full 50% add, 50% elev, 100% abd Full 70% add, 90% elev. 100% abd 80% dep, 40% dep, , 15% dep, 10% dep, 60% dep, , 80% dep, Arteriogram 6/ 12 6/ 12 6/ 9 6/ 9 6/ 9 6/ 9 6/ 7.5 6/ 7.5 6/ 7.5 6/ 7.5 6/ 6 6/ 6 6/ 12 6/ 21 6/ 7.5 6/ 12 6/ 9 6/ 7.5 6/ 15 6/ 9 Pupil size ( mm) 8.0 5.0 3.0 5.0 3.5 4.5 4.5 5.5 5.0 4.0 3.5 3.0 5.0 7.0 4.5 5.0 4.0 6.0 3.0 5.0 ( vessels injected/ results) Complications Right carotid, left vertebral Complete right internal carotid occlusion Left internal carotid, right internal carotid, left vertebral Negative Magnetic resonance angiography Negative Left internal carotid, left vertebral Negative Right internal carotid Negative Left internal carotid, left vertebral Negative Left internal carotid Negative Right internal carotid, left internal carotid Negative Left internal carotid, left vertebral Negative Left internal carotid, left vertebral Negative None None None None None None None None None None a M = male, F = female; OD = right elevation. " Denotes affected eye. eye, OS = left eye; add = adduction, abd = abduction, dep = depression, elev / Nciiw- Ophllmlmol, Vol. 15, No. .3, 1995 THIRD NERVE PALSIES 139 FIG. 1. Case 2 on initial presentation. Photograph demonstrates limited up- gaze, down- gaze, and adduction of the left eye. ( Arrows indicate direction of gaze.) Note the 2 mm of anisocoria. ( Reprinted with permission from Swartz, NG, and Savino, PJ, Manifestations of lesions in the suprasellar and parasellar regions: a neuro- ophthalmologic perspective. Seminars in Ultrasound, CT, and MRI. 14( 3): 206- 14.) rysms ( 5- 7). In 1983, Kissel and associates ( 5) published a retrospective review of internal carotid-posterior communicating artery aneurysms. At presentation 21/ 51 patients had partial oculomotor palsies. Of these partial oculomotor palsies, 14/ 21 had pupillary involvement at the onset of the palsy and five of the remaining seven progressed to pupillary involvement. Three of 51 patients with aneurysm had relative pupillary sparing. In addition to patients with aneurysms presenting with pupillary sparing, those with vasculo-pathic third nerve palsies demonstrating some degree of sphincter impairment are also common in the literature. In Green's series ( 3), 8/ 25 patients with diabetic third nerve palsies had pupillary involvement. Of the eight patients with pupillary involvement, four had a dilated and fixed pupil and four had a dilated and reactive pupil. Rucker ( 4) reported that in patients with vasculopathic third nerve palsies, 11/ 63 patients showed pupillary abnormalities. In Goldstein and Cogan's ( 8) series of diabetic ophthalmoplegia, 5/ 22 patients had pupillary involvement, and four of these five appeared to have relative pupillary sparing. It is clear that there is considerable overlap in clinical presentation of patients with third nerve palsies secondary to aneurysms and those due to microvascular disease. There exists a subset of patients that does not fit strictly into one of the two categories of complete pupillary involvement or complete pupillary sparing. These are the patients that present with partial or complete external ophthalmoplegia with some degree of, but not total, pupillary involvement ( i. e., relative pupillary sparing)- This clinical overlap can make it difficult to determine the appropriate management of the patient that presents with relative pupillary sparing. The major diagnostic decision is whether to subject the patient to cerebral arteriography, with its attendant risks, to exclude an intracranial aneurysm. The reported morbidity of cerebral arteriography ranges from 0.0% to 28% and variability among institutions is high. In recent years, there has been a trend toward lower complication rates ( 9- 12). The morbidity of arteriography must be weighed against the probability of identifying a treatable lesion. Our ten consecutive patients with relative pupillary sparing third nerve palsies were free of aneurysm on cerebral angiography or MRA. None of the patients experienced a complication secondary to invasive imaging. We recognize that the number of patients enrolled in this study is small; however, this is an uncommon condition. There may also be a selection bias since all patients presented as outpatients to a neuro- ophthalmology service and seven of ten patients had symptoms for more than one week. This type of presentation may be selecting for patients free of intracranial pathology. As previously stated, all patients were in the vasculopathic age / Neuro- Ophthahnol, Vol. 15, No. 3, 1995 140 CULLOM ET Ah. group; in a younger subset of patients, the incidence of aneurysm may be higher. Until now, the appropriate management of patients with relative pupillary sparing third nerve palsies was not clearly defined. Most neuro-ophthalmologists tended to consider this entity as pupil sparing and treated patients conservatively. Our study appears to support this behavior; it appears that the incidence of aneurysm in this subset of third nerve palsies is low. We recognize that it has been reported that patients with relative pupil sparing may harbor an intracranial aneurysm ( 5). However, the incidence of aneurysm may be low enough to preclude the need for routine cerebral angiography in this group of patients. The exact role for MRA in detecting aneurysms smaller than 3 mm awaits further clarification. REFERENCES 1. Trobe JD. Third nerve palsy and the pupil. Arch Ophthalmol 1988; 106: 601- 2. 2. Ross JS, Masaryk T], Modic MT, et al. Intracranial aneu- In this issue of the journal, Cullom et al. propose that " the prevalence of aneurysm in patients with relative pupillary sparing third nerve palsies may be low enough to preclude the use of routine angiography." The paper obviously attempts to address a well- known problem: how to manage third nerve palsies that do not fit the rule of the pupil? The rule of the pupil applies to patients in the vasculopathic age group who have acute, isolated oculomotor palsies with complete external ophthalmoplegia. In such patients, obvious pupillary involvement ( mydriasis, poor reactivity) warrants emergent noninvasive imaging, followed, if negative, by cerebral angiography in search of a " posterior communicating artery" aneurysm. Pupillary sparing ( no anisocoria, normal reactivity) is assumed to imply small vessel ischemia ( mononeuritis multiplex) and is managed medically/ conservatively. When the rule of the pupil does not apply, i. e., when either the ophthalmoplegia and/ or pupillary involvement is incomplete, the clinician's dilemma becomes whether to angiogram or not to angiogram. No reliable guidelines exists on how to manage incomplete third nerve palsies. Without such guidance, neuro- ophthal-rysms: evaluation by MR angiography. Am ] Neuroradiol 1990; 11: 449- 56. 3. Green WR, Hackett ER, Schlezinger NS. Neuro- oph-thalmologic evaluation of oculomotor nerve paralysis. Arch Ophthalmol 1964; 72: 154- 67. 4. Rucker CW. Paralysis of the third, fourth, and sixth cranial nerves. Am J Ophthalmol 1958; 46( 6): 787- 94. 5. Kissel JT, Burde RM, Klingele TG, et al. Pupil sparing oculomotor palsies with internal carotid- posterior communicating artery aneurysms. Ann Neurol 1983; 13( 2): 149- 54. 6. Kasoff I, Kelly DL. Pupillary sparing in oculomotor palsy from internal carotid aneurysm. / Neurosurg 1975; 42: 713- 7. 7. Bartleson D, Trauttman JC, Sundt TM. Minimal oculomotor nerve paresis secondary to unruptured intracranial aneurysm. Arch Neurol 1986; 43: 1015- 20. 8. Goldstein JE, Cogan DG. Diabetic ophthalmolplegia with special reference to the pupil. Arch Ophthalmol 1960; 4: 144- 52. 9. Faught E, Trader SD, Hanna GR. Cerebral complications of angiography for transient ischemia and stroke: prediction of risk. Neurology 1979; 29: 4- 15. 10. Earnest F, Forbes G, Sandok BA, et al. Complications of cerebral angiography: prospective assessment of risk. Am ] Neuroradiol 1983; 4: 1191- 7. 11. Hankey G, Warlow CP, Sellar RJ. Cerebral angiographic risk in mild cerebrovascular disease. Stroke 1990; 21: 209- 22. 12. Dion JE, Gates PC, Fox AT, et al. Clinical events following neuroangiography: a prospective study. Stroke 1987; 18( 6): 997- 1004. mologists at times make difficult decisions based more on the art than the science of medicine. Sometimes the concept of " relative pupil sparing" is invoked; however, that is an entity which unfortunately does not have a uniformly accepted definition. Cullom et al. seem to have a very liberal definition of relative pupil sparing, allowing for incomplete extraocular muscle paresis with or without some pupillary involvement. It is my bias that a relative pupil sparing oculomotor palsy exists when there is complete external ophthalmoplegia and only minimal pupillary involvement, i. e. the pupillary abnormality is disportion-ately mild when compared to the otherwise complete paralysis of the extraocular muscles. When the latter definition is met, some neurooph-thalmologists, perhaps with trepidation, manage the patients conservatively on the assumption that the etiology is vasculopathic, nonaneurysmal and therefore not deserving emergent cerebral angiography. Practically every conceivable variation on the theme of a partial ophthalmoplegia and pupillary abnormality has been reported as a manifestation of aneurysmal compression; therefore prudence Commentary: Isolated Incomplete Third Nerve Palsies in the Vasculopathic Age Group: To Angiogram or Not to Angiogram- That Is the Question. / Ncuro- Ophthatmol Vol. 15, No. 3, 1995 THIRD NERVE PALSIES- COMMENTARY 141 would suggest that angiography should be the rule rather than the exception in cases that do not obey the rule of the pupil. Since every acute incomplete third nerve palsy is a potential harbinger of impending aneurysmal rupture, it would be very helpful to know how frequently incomplete oculomotor palsy is due to an aneurysm. A large, preferably prospective series is needed to provide information about the incidence of aneurysm in patients with partial oculomotor palsy. What is troublesome about the paper by Cullom et al. is that it draws conclusions on the basis of a very small patient sample. A series of ten cases is so small that it provides insufficient guidance on how to manage patients. If the authors' next clinical case proved to be aneurysmal, then they would have to conclude that the incidence of aneurysm with relative pupillary sparing ( as defined in their paper) is close to 10%. Such statistics would clearly argue in favor of proceeding with cerebral angiography in their cases. In short, the conclusions of the paper by Cullom Commentary If it is true that there is considerable overlap in the clinical presentation of patients with oculomotor pareses, be they aneurysmal or microvascular, how is the clinician to behave when such patients are evaluated? To arteriorgram, or not? The paper by Cullom et al. published in this journal suggests that one may err on the side of caution- that is, angiography is not imperative- when there is relative pupillary sparing. From a series of ten, these authors argue that relative pupillary sparing may be treated as pupil sparing. They base this supposition upon reasoning that the incidence of aneurysm in this subset of third nerve palsies is low, indeed, low enough to preclude the use of routine angiography. We disagree with these conclusions. Given that the authors admit " it has been reported that patients with relative pupillary sparing may harbor an intracranial aneurysm," and given Kissel's published observations that three of 51 patients with aneurysm and oculomotor weakness had relative pupillary sparing, we believe to err on the side of caution is to do the angiogram. For the clinician seeing and taking care of patients, it is imperative to separate what one thinks and how one behaves. We may think the likelihood of an aneurysm to be low, but we must behave in a manner that does not overlook its presence. The yield of finding an aneurysm in the patient whose pupil is partially spared yet shows third nerve involvement may be et al. are based on too small a sample and therefore their recommendations are premature. What is needed is the publication of a much larger series evaluating patients in the vasculopathic age group presenting with acute, isolated incomplete oculomotor palsies. Such a study could provide data about the incidence of aneurysm as well as about the potential prognostic difference between pupil-sparing and pupil- involving partial third nerve palsies. A well- designed, prospective study could perhaps best be completed by combining data from several institutions represented by readers of the journal. Until the recommendations of Cullom et al. are confirmed by such a study, it appears prudent to err on the side of ordering too many rather than too few angiograms. Thomas L. Slamovits, M. D. Bronx, New York lower than previously thought, but not to uncover an aneurysm that is changing and causing a new cranial neuropathy may on more than an occasional basis be disastrous for that patient. It is an error of omission that ought not be made in this day and age. Recognizing the aneurysm allows us to treat a cause of stroke, perhaps the most treatable cause of stroke; while more patients will be angiogramed than aneurysms discovered, for the patient with the aneurysm, prognosis ought be dramatically changed by its recognition and successful remedy. A converse statement is also true: for the physician who fails to recognize an aneurysm in the patient presenting with new cranial neuropathy, his future too would be clouded. We therefore take the opposite perspective of the authors of this paper, and say, for the average clinician, considering your average third nerve paresis, the differentiation should be, is the pupil involved or is it not? If it is involved at all, be it minimally, relatively, or sparingly, a compressive lesion ( statistically most likely an aneurysm) must be ruled out. While this rule is not inviolate, we ask that it only be violated by the neuro- ophthalmologist, not the general community of practicing physicians. Barrett Katz, M. D. San Francisco, California / Neuro- Ophthalmol, Vol. 15, No. 3, 1995 |
