Volume 81, Issue 10 , Pages 505-509, October 2010
Normal pupil findings can give a false sense of security in a presumed cranial nerve III palsy patient: A unique case report
Article Outline
Abstract
Background
A cranial nerve (CN) III palsy can be caused by a life-threatening aneurysm, typically of the posterior communicating artery. The “rule of the pupil” states the majority (96%) of such cases will present with abnormal pupil findings caused by compression of the fibers, located superficially along CN III. Careful examination of the size and reactivity of the pupils is critical.
Case Report
This case describes the complex management of a 79-year-old man with sudden-onset ptosis and diplopia consistent with a superior division CN III palsy. The pupils were normal, but because of the incomplete nature of the palsy the “rule of the pupil” could not be applied, and an aneurysm remained a threat. After urgent testing, microvascular infarct was deemed the cause. However, the palsy failed to resolve after 3 months. Further investigation found myasthenia gravis as the final diagnosis.
Conclusions
Several important points are outlined regarding CN III palsies. First, lack of pupil involvement in an incomplete palsy is not equivalent to pupil sparing in a complete palsy. Second, after initial diagnosis, if subsequent findings are no longer consistent, further investigation is warranted. Lastly, myasthenia gravis should be considered as a differential in apparent palsy cases.
Keywords: Partial third-nerve palsy, Aneurysm, Pupillary disorders, Myasthenia gravis
Cranial nerve (CN) III, the oculomotor nerve, innervates the levator palpebrae superioris and 4 of the 6 extraocular muscles (superior rectus, inferior rectus, inferior oblique, and medial rectus) and also supplies parasympathetic innervation to the sphincter muscle of the iris and to the ciliary body. CN III plays a role in lid elevation, pupillary constriction, accommodation, and the majority of extraocular muscle movement.
Dysfunction of CN III has a variety of etiologies. In adults, the most common are trauma, microvascular disease (peripheral nerve infarction), and life-threatening aneurysms.1 The average time from onset of an aneurysm-caused CN III palsy to rupture, with a subsequent subarachnoid hemorrhage, is 29 days.2 Treatment of the aneurysm before rupture is beneficial; therefore, prompt and accurate diagnosis is critical.
Depending on the structures involved, oculomotor palsies can have variable presentations. The pupil can be normal or fixed and dilated, the lid may be normal or ptotic, strabismus will be variable depending on the extraocular muscles (EOMs) involved, and the palsy may be isolated, or other cranial nerves may also be affected. Clinical findings may help locate the lesion along the course of the nerve and establish the etiology. A brief review of CN III anatomy follows:2 the nucleus, made up of subnuclei, begins at the dorsal midbrain. All subnuclei project ipsilaterally with the exception of the superior rectus, which innervates the contralateral side, and the levator subnucleus, which innervates both sides. The third nerve fascicle travels ventrally near the red nucleus and corticospinal tract. As it enters the subarachnoid space, it runs between the posterior cerebral and superior cerebellar arteries and parallel to the posterior communicating artery. The nerve then travels through the lateral side of the cavernous sinus and enters the orbit through the superior orbital fissure. At this point, the nerve splits into 2 divisions: superior division (innervates the levator and superior rectus) and inferior division (innervates the pupil and the remaining 3 EOMS). Importantly, there is topographic separation of these 2 divisions within the nerve before it splits. The pupillary fibers travel on the dorsomedial, superficial portion of the nerve.
During its course, the different regions of the oculomotor nerve are susceptible to a variety of insults. A head injury, for example, can cause CN III dysfunction at the nuclear or fascicular portion via a hemorrhage or at the superior orbital fissure or in the cavernous sinus via a bone fracture.3 A microvascular peripheral nerve infarct affects the core of the nerve, where the blood vessels run, and likely spares the pupil fibers. By contrast, a compressive lesion, such as a tumor or aneurysm, would abut the pupillary fibers because of their superficial location on the CN III and impair their function. Thus, the “rule of the pupil” which states a compressive lesion will present with abnormal pupil findings, specifically fixed and dilated, on the involved side. The posterior communicating artery or its junction with the internal carotid artery are the most common sites of aneurysm formation involving CN III. Other potential locations include the superior cerebellar, basilar, and posterior cerebral arteries.
Oculomotor palsies are either classified as complete or incomplete. A complete CN III palsy involves the levator and all 4 of the EOMs, which causes a downward and outward deviation of the eye with an ipsilateral ptosis. An incomplete CN III palsy involves a subset of these structures, often only 1 of the 2 divisions of the nerve, and the presentation will vary. These 2 types of CN III palsy require different management.
An isolated palsy means no other neurologic signs are present (i.e., headache, pain, other cranial nerve involvement). Pupil sparing is defined as less than 1 mm anisocoria and normal pupillary light reflex.2 A review of the management of an acquired, complete, isolated CN III palsy with pupil sparing follows: If the patient is older than 40 years with known systemic vascular disease, such as diabetes, hypertension, or atherosclerosis, close observation for the first few days is required to monitor for delayed pupil involvement. For maximal ophthalmoplegia, the average time from onset is 3 days.2 If no pupil involvement occurs during this time, an aneurysm is highly unlikely, imaging is generally not required, and the patient can be observed for improvement over the next several weeks. Trobe4 states the odds are 40:1 for a pupil-spared, complete CN III palsy to be a microvascular infarct rather than another etiology.4 Of course, if the pupil does become involved at any point, urgent imaging is required.
In a patient with an acquired, incomplete CN III palsy, an aneurysm could be present, even though the pupils are not involved. Up to 30% to 40% of incomplete palsies may be caused by an aneurysm.2 Urgent imaging is required, regardless of the pupil findings, because the segregation of the 2 divisions within CN III can lead to paresis of only one division because of partial insult to the nerve anywhere along its course to the orbit, as early as the midbrain. The pupil fibers run with the inferior division of CN III, so an aneurysm pressing only on the superior division fibers may leave the pupil fibers unaffected. The result would be a patient with a ptosis, superior rectus restriction, and pupil-sparing harboring an aneurysm. Therefore, the “rule of the pupil” does not apply to incomplete cases.
Case report
A 79-year-old white man presented to our clinic with complaint of complete left lid closure for 2 weeks with no variation throughout the day. In addition, he noted vertical double vision when the lid was lifted. He denied any associated symptoms such as eye or head pain, numbness, tingling, ataxia, or blurred vision. The onset was rather sudden and there was no history of ocular or head trauma. The patient stated no improvement had occurred in the 2-week time period.
His ocular history was positive for cataract extraction in the left eye, mild cataract in the right eye, and early macular degeneration in both eyes. His systemic medical history was positive for non-insulin–dependent diabetes mellitus, atrial fibrillation, hyperlipidemia, allergic rhinitis, cardiomyopathy, asthma, hypertension, and hearing loss. His last HbA1c reading was 6.7% 1 month prior.
Ocular examination found the best-corrected visual acuity to be 20/25 in both eyes with Snellen acuity testing. He had a complete ptosis of the left lid. No proptosis was present. During distance cover test in primary gaze, a 9–prism diopter left hypotropia was measured with no horizontal component. Extraocular motility found a left eye superior restriction. Subjective diplopia was reported on primary gaze, which was worse when attempting elevation/abduction and on left head tilt. Park's 3-step isolated the left superior rectus muscle. Confrontation fields were full (when left lid was lifted). Both pupils were briskly reactive with no afferent pupillary defect or anisocoria. Other neurologic testing found normal corneal and facial sensitivity with a cotton wisp (CN V), a symmetric smile and expected orbicularis oculi function based on failed attempt to open tightly squeezed lids (CN VII), normal sternocleidomastoid function based on expected muscle strength with resistance to head turn in both directions (CN XI), previously established hearing loss, good articulation of words, and no trouble with swallowing or breathing based on patient questioning. The patient denied any symptoms of giant cell arteritis. All other examination findings were consistent with those of prior examinations.
Ocular myasthenia was a differential for this patient based on ptosis and diplopia, but several findings made this seem less likely: the involvement of only 1 EOM and the ptosis had a sudden onset, was complete, unilateral, and did not vary throughout the day. Therefore, we concluded the most likely diagnosis was an insult to the superior division of his left CN III. This was consistent with the involvement of only the patient's levator palpebrae superioris and superior rectus muscles. Potential etiologies of superior division only CN III palsies include microvascular infarction, postviral, aneurysm (specifically, posterior cerebral, basilar apex, superior cerebellar arteries), cavernous sinus or intraorbital mass, midbrain infarction, meningitis, sphenoid sinusitis, trauma, or giant cell arteritis.5
We sent the patient for a Westergren sedimentation rate (sed rate), C reactive protein (CRP) level, and complete blood count (CBC). We scheduled head and orbit imaging, magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA), which has the ability to detect aneurysms with a diameter of 5 mm or larger. We also made a referral to neuro-ophthalmology. The sed rate was 22 mm/h, CRP was normal at 2.77 mg/L, and the CBC was normal. For a 79-year-old man, an abnormal sedimentation rate would be levels greater than 39.5 mm/hour (age/2).6, 7 We saw him the next day to detect further ophthalmoplegia, but all findings were stable, including pupils. His imaging was conducted the next day and showed no aneurysm, mass, or infarction (see Figure 1). He did have paranasal sinusitis, an unrelated finding, which was reported to his primary care doctor. Given the patient's age, lack of trauma history, medical history (diabetes and hypertension), and normal blood work and imaging, we diagnosed microvascular, incomplete CN III palsy. We encouraged the patient to keep tight blood sugar and blood pressure control and to call with any changes in symptoms.
Figure 1
MRA of Circle of Willis, arrow pointing to posterior communicating artery, no aneurysm present.
The Neuro-ophthalmology Department saw the patient on day 3 and agreed with our diagnosis. The patient followed up with the optometry service 3 weeks later (roughly week 6). The ptosis was stable, but the diplopia had improved, present only on attempted upgaze. At follow-up 6 weeks later, the ptosis and the left hypotropia were still present. No signs of aberrant regeneration were found. The ice test increased the palpebral fissure size from 5 mm to 10 mm on the left side. Cogan's lid twitch was not present. After fatiguing the levator with 1 min of sustained upgaze, the palpebral fissure narrowed from 5 mm to 2 mm (see Figures 2 and 3). Because of the results of these tests and the failure of this supposed microvascular palsy to resolve in 3 months, we referred the patient back to neuro-ophthalmology with ocular myasthenia now the most likely diagnosis.
Figure 2
Palpebral fissure size pre-sustained upgaze test.
Figure 3
Decreased palpebral fissure size status post-sustained upgaze test.
One month later, the ophthalmologist measured a 2–prism diopter left hypotropia on cover test. Orders were placed for serum Acetylcholine (Ach) receptor antibody levels and a head computed tomography (CT) scan. CT, which is best for imaging bone, can detect a mass located adjacent to bone. The CT showed no mass (see Figure 4), but the Ach receptor antibodies were 1.77 nmol/L (normal is <0.38). The patient was referred to the Neurology Department where repetitive nerve conduction findings were consistent with a neuromuscular transmission disorder. The patient had myasthenia gravis (MG) diagnosed, which was responsible for the levator and superior rectus impairment. The patient was started on pyridostigmine (acetylcholinesterase inhibitor) by mouth, 30 mg twice a day.
Figure 4
CT scan of head and orbits, no mass present.
A month later, the patent noted the lid droop was improved but worsened at the end of the day. The diplopia was present only on upgaze (4-prism diopter left hypotropia). At this point, the pyridostigmine dose was increased to 60 mg twice a day. A chest CT was ordered to rule out a thymoma, a tumor of the thymus gland present in roughly 15% to 20% of MG patients.8 No thymoma was found (see Figure 5). The patient did well on treatment and never experienced any further systemic effects of MG.
Figure 5
CT of the thorax, the arrow points to where the thymoma would be located, if it were present.
MG is a chronic, acquired, autoimmune neuromuscular disorder that is most commonly diagnosed in young adult women or older men but can occur at any age. The prevalence is 4 to 5/100,000.9 In this condition, antibodies block, alter, or destroy acetylcholine receptors at the neuromuscular junction, preventing normal muscle contraction. The result is weakness and fatigability of the skeletal muscles of the body. Nonocular findings can include dysarthria, dysphagia, difficulty holding head upright, and respiratory failure, termed myasthenic crisis, in advanced cases.
During the course of their disease, up to 87% of MG patients will have ocular signs, and in as high as 60% these signs will be the first clinical manifestation of the disease.9 The involved structures can include 1 or all of the following structures: the levator, orbicularis oculi, and the EOMs. The clinical signs include ptosis, orbicularis oculi weakness, and ophthalmoplegia, which tend to be worse at the end of the day or with fatigue. The pupils will be unaffected.
During an eye examination, several tests can be performed to aid in the diagnosis if MG is suspected. First, testing for Cogan's lid twitch begins by asking the patient to look down for about 15 seconds. When asked to move to primary gaze, an overshoot of the ptotic lid is observed followed by a return to the original ptotic position in a twitchlike manner.9 Second, the ice test is performed by measuring the palpebral fissure size before and after an ice bag is placed on the eye for 5 minutes (the other eye can be measured before and after, too, as a control). In MG, the palpebral fissure size should temporarily increase on the iced eye likely because of reduced effect of acetylcholinesterase at the neuromuscular junction.9 This test is more than 95% sensitive and 100% specific for MG.9 Lastly, the sustained upgaze test is performed by first measuring the palpebral fissure size, and then the patient looks straight up for 1 minute. In MG, the palpebral fissure size is expected to decrease because of fatiguing due to insufficient Ach receptor activation. In those without MG, the palpebral fissure size would not change with these tests.
Discussion
Oculomotor palsies can present with a variety of signs and symptoms and have several possible etiologies, some more urgent than others. This case highlights several important management points for such cases. First, the pupil findings are considered an extremely important indicator for the presence of an aneurysm or tumor in CN III palsies. A compressive lesion disrupts the superficial pupil fibers and causes a fixed, dilated pupil. If an incomplete CN III palsy is present, normal pupillary findings can portray a false sense of security. The pupillary fibers run with the inferior division of CN III; therefore, a superior division palsy may still be harboring an aneurysm. Prompt imaging is required.
Second, microvascular etiology, an infarction to the core of the nerve, accounts for up to 40% of CN III palsies.4 These cases should resolve in 3 months. In a study of 28 patients with ischemic CN III palsy, 68% resolved in 4 weeks, 96% in 8 weeks, and 100% in 12 weeks.10, 11 In our case, the patient continued to have ptosis and variable diplopia at the 12-week examination. This prompted additional diagnostic testing. High Ach receptor antibody levels and abnormal nerve conduction testing found ocular myasthenia gravis as the cause for the patient's diplopia.
Lastly, the presentation of initial, systemic signs of MG often are ocular; therefore, eye care practitioners play an important role in the diagnosis of this condition. Without detection, the patient is at risk for potentially harmful systemic ramifications of myasthenia gravis. MG should be considered in all diplopia patients, especially if the diplopia is variable and an accompanying ptosis is present.
Conclusion
As primary eye care providers, our role is to promptly and accurately diagnose and manage oculomotor palsies, as well as all acutely diplopic patients. We must be able to recognize those who require immediate imaging versus those who can be managed by observation. This case report shows the complex management of a diplopic patient in whom a clear understanding of pupil findings dramatically altered the urgency of diagnostic testing.
Acknowledgment
The author thanks Timothy Harkins, O.D., Julie Grove, O.D., and her father, Terry Dougherty, for reviewing the manuscript before submission.
References
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PII: S1529-1839(10)00251-4
doi:10.1016/j.optm.2010.03.007
© 2010 American Optometric Association. Published by Elsevier Inc. All rights reserved.
Volume 81, Issue 10 , Pages 505-509, October 2010
