Schwannomas, or neuromas, of the cranial nerves are uncommon, comprising 8% of all primary intracranial tumors and most commonly affecting the vestibular nerve or trigeminal nerve (1). Schwannomas of the third and fourth nerves are rare as are those of the sixth nerve, although the sixth nerve may be affected by schwannomas of the fifth nerve. Cranial nerve schwannomas may be asymptomatic, present clinically with dysfunction of the nerve from which they arise or may cause dysfunction of neighboring cranial nerves. Typically the clinical course of schwannomas is one of progressive cranial nerve dysfunction or relative stability, (2) but some reports have documented that transient or recurring symptoms may also occur (2–8). Remission of ocular motor and visual symptoms has also been reported with other types of mass lesions, such as meningiomas, chordomas, and optic nerve gliomas (9–14).
The following is a report of 10 cases of presumed cranial nerve schwannoma that presented with transient or recurring ocular motor deficits.
A 41-year-old woman with diabetes mellitus presented with a pupil-involving left third nerve palsy associated with severe headache. She had a history of “migraine headaches” since age 23 years. Brain computed tomography (CT) and cerebral angiography were normal. She was diagnosed with ophthalmoplegic migraine. Her symptoms gradually resolved over the next 6 months.
Ten years later, the left third nerve palsy and headache recurred. Serologic and cerebrospinal fluid (CSF) studies were normal. Brain magnetic resonance imaging (MRI) revealed a thickened and enhancing 3-mm nodular lesion of the left third nerve within the interpeduncular cistern, consistent with a schwannoma. She was empirically treated with a short course of oral prednisone. Gradually, over the next 6 months, the third nerve palsy resolved. A follow-up MRI, 12 years after her initial presentation, showed no change in the size or nodular enhancement of the third nerve lesion (Fig. 1A).
She had a third episode 13 years after her initial presentation. A repeat brain MRI was unchanged, and magnetic resonance angiography revealed no vascular abnormalities. Once again, her third nerve deficits resolved slowly over time, and she has remained asymptomatic for the past several years.
A 23-year-old woman developed a complete pupil-involving right third nerve palsy accompanied by a severe headache. She reported having experienced a total of 5 similar stereotyped episodes beginning at age 7, with normal intervening neurologic and ophthalmologic examinations and had previously been diagnosed with “ophthalmoplegic migraine.” Brain MRI revealed a 4-mm nodular enhancing lesion of the right oculomotor nerve within the interpeduncular cistern. Her headache was treated with analgesic medications, and the right oculomotor nerve palsy resolved within 1 week (previously reported (5)).
Seven years later, she had her seventh episode of “ophthalmoplegic migraine.” On brain MRI, the appearance of the right third nerve lesion was unchanged (Fig. 1B). Once again, her third nerve palsy resolved spontaneously. Six months after resolution of her symptoms, a third brain MRI revealed continued nodular enhancement of the right oculomotor nerve lesion.
A 42-year-old man presented with a partial pupil-involving left third nerve palsy accompanied by headache and periorbital pain. For the previous 15 years, he had been experiencing similar left periorbital headaches once or twice a year that were unaccompanied by other symptoms.
Brain MRI showed focal enlargement and nodular enhancement of the left third nerve at its brainstem exit. Six weeks later, the ptosis and extraocular movements in the left eye had improved significantly. Ten months later, only minimally decreased elevation of the left eye was noted. Repeat brain MRI at that time showed no change in the nodular enhancement of the left third nerve lesion.
A 43-year-old man with isolated complete paralysis of the right medial rectus muscle was evaluated with serologic testing and CSF analysis that were unremarkable. Brain MRI revealed nodular enlargement and enhancement of the inferior division of the right third nerve. He received a 10-day course of oral prednisone. The right medial rectus paresis gradually improved over a 3-month period leaving only a small exophoria that increased on left gaze. Repeat MRI scans 6 months and 2 years later showed no interval change.
The patient returned 9 years later with recurrence of isolated complete paralysis of the right medial rectus muscle. Repeat MRI again showed similar nodular enlargement and enhancement of right inferior division of the third nerve (Fig. 2A). The diplopia and ophthalmoplegia resolved in over 5 months. Repeat MRI 10 months after his second presentation and 6 months after symptom resolution showed no interval change (Fig. 2B). Follow-up examination was normal except for a small exophoria that increased on left gaze.
A 36-year-old man with diplopia was diagnosed with a right fourth nerve palsy. His medical history was significant only for asthma. Serologic testing and CSF studies were normal. Brain MRI showed focal enlargement and enhancement of the right trochlear nerve adjacent to the midbrain (Fig. 3A). The diplopia gradually resolved over several months, but brain MRI 3 years later was unchanged (previously reported (2)).
He remained asymptomatic for many years, except for 2 episodes of mild transient diplopia. Repeat brain MRI 10 years after initial presentation showed no change in the enhancing right fourth nerve lesion (Fig. 3B).
A 60-year-old man with diabetes mellitus and hyperlipidemia developed a right fourth nerve palsy. Serologic testing was normal. A noncontrast brain MRI revealed a small isointense lesion of the right trochlear nerve adjacent to the midbrain. His diplopia gradually resolved without treatment, and on follow-up examination 3 months after presentation, there was no residual vertical misalignment (previously reported (2)).
Approximately 6 months later, he reported recurrence of binocular vertical diplopia and examination revealed a right fourth nerve palsy. Contrast-enhanced brain MRI demonstrated nodular enhancement of the previously identified trochlear nerve lesion, consistent with a schwannoma. The diplopia gradually resolved without treatment. Repeat examination 1 year later revealed a slight left head tilt and a small right hyperphoria.
A 48-year-old man with a right fourth nerve palsy had serologic studies and an edrophonium test that were negative. Brain MRI showed an enhancing right trochlear nerve lesion. Over the next year, his diplopia resolved spontaneously, leaving no residual findings on examination (previously reported (2)).
He remained asymptomatic, and his examination remained normal on follow-up 7 and 9 years after initial presentation. More than a decade after presentation, brain MRI showed continued enhancement of the right fourth nerve lesion.
A 66-year-old man reported a 6-month history of binocular vertical diplopia. Examination showed a right fourth nerve palsy, and brain MRI revealed an enhancing lesion of the right fourth nerve. After attempts at prism correction were unsuccessful, he was referred to a strabismus surgeon, but by the time he was seen, approximately 8 months later, his symptoms had spontaneously resolved.
He has remained asymptomatic, but follow-up MRI 4 years after his initial presentation showed that the enhancing fourth nerve lesion was still present.
A 43-year-old man with a history of pulmonary sarcoidosis and diabetes mellitus was found to have a right sixth nerve palsy. Laboratory studies including CSF analysis were normal. Whole-body SPECT gallium scanning was unremarkable. Brain MRI demonstrated an enhancing lesion within Meckel cave on the right, extending to the cavernous sinus (Fig. 4A).
Although his diplopia resolved spontaneously, he received an 8-week course of oral corticosteroids. Brain MRI after steroid treatment revealed no interval change in the enhancing lesion. His examination remained normal at a 6 month follow-up visit.
Approximately 2 years after his initial presentation, the patient returned with a right fourth nerve palsy. His diplopia gradually resolved over 6 weeks without treatment, and his examination returned to normal. He remained asymptomatic for the next 5 years with a normal examination. Follow-up brain MRI 7 years after initial presentation (Fig. 4B) showed no change in the appearance of the enhancing trigeminal nerve lesion.
A 43-year-old woman presented with a right sixth nerve palsy. Identical events had taken place as many as 10 times in the previous 14 years. Each attack would come without warning, regress spontaneously after 6 to 12 weeks and occur approximately once a year. She had been free of attacks for as long as 4 years but had also once had 2 attacks in the same year.
Six weeks after her presentation, her diplopia resolved and a follow-up examination was normal. A detailed physical examination revealed a nodule on her left leg that appeared to be a schwannoma. Although the patient had no subjective hearing complaints, an audiogram revealed left sensorineural hearing loss. Brain MRI performed 2 years previously showed multiple enhancing lesions within the frontal lobes, cerebellopontine angles, and Meckel cave. The frontal lobe lesions were most consistent with meningiomas; the other lesions appeared to be left vestibular and right fifth nerve schwannomas. During follow-up over several years, there was no change in the intracranial abnormalities. The patient was diagnosed with neurofibromatosis type 2. She has subsequently had 2 other identical episodes of horizontal diplopia, both of which resolved spontaneously.
In our case series, the ocular motor symptoms from schwannomas were transient or recurring (Table 1). Of our 10 patients, 4 involved the third nerve, 3 of which were clinically suggestive of ophthalmoplegic migraine. Four cases involved the fourth nerve in isolation and 2 involved the fifth nerve within Meckel cave, leading to palsies of the sixth nerve in 2 cases, one of which had a fourth nerve palsy as well. In all 9 cases with follow-up MRI studies, the location of the lesions and the persistent nodular enhancement, even when asymptomatic, were most consistent with schwannoma.
In patients with involvement of the cisternal segment of the third nerve, ptosis and diplopia were accompanied or preceded by headache, often with migrainous features, creating a clinical picture indistinguishable from ophthalmoplegic migraine. Many reported cases of ophthalmoplegic migraine are associated with focal thickening and enhancement of the third nerve at its brainstem exit and, because both the focal swelling and enhancement typically resolve once the oculomotor palsy remits, it has been argued that the pathology in this migraine disorder is transient inflammation or demyelination (15). Some have dismissed the idea that schwannoma can present with recurrent symptoms (16). In our patients, both focal enlargement and enhancement persisted even during periods of clinical remission, favoring the possibility that schwannoma may be the underlying pathology in at least some cases of ophthalmolplegic migraine.
Although a diagnosis of schwannoma can often be made presumptively based on neuroimaging characteristics, a definitive diagnosis requires tissue examination. Our patients had MRI during the acute palsy and after resolution, and these were all carefully reviewed by neuroradiologists to rule out other pathological processes. None of our patients underwent biopsy or surgical resection as the symptoms generally resolved and because evidence suggests that tumor resection may lead to permanent cranial nerve deficits (4). Despite the absence of histologic proof, we believe that it is reasonable to make a presumptive diagnosis of schwannoma in our patients.
We are aware of 3 reported cases with enhancing cranial nerve lesions, which had initially presented with transient ocular motor cranial nerve deficits and that were subsequently biopsied or resected (6–8). In all 3 cases, enhancing lesions of the third nerve were associated with transient ptosis, diplopia, and headache, mimicking ophthalmoplegic migraine. Histopathologic examination of all 3 lesions revealed schwannoma.
We have not encountered any cases of schwannoma of the sixth nerve causing transient diplopia, but in 2 of our patients, schwannoma of the fifth nerve within Meckel cave resulted in transient palsies of the sixth nerve. In both, there were no symptoms of fifth nerve dysfunction. This has been noted in other cases in which sixth nerve palsy was an initial manifestation of fifth nerve nerve schwannoma (17).
No definitive explanation is available for the clinical fluctuations that we observed, particularly given the relative stability of the MRI lesions. There are other reports of clinical improvement with mass lesions whose size remained unchanged over time (10–13). Proposed mechanism for remissions or fluctuations includes regression of tumor-associated edema, remyelination, and hemodynamic changes.
The expected clinical course of schwannoma is one of stability or slow progression, but as we and others have demonstrated, it may be one of fluctuating signs and symptoms (2–8). Clinicians should be aware of the possibility of schwannoma as a cause of ocular motor cranial nerve palsy with a relapsing or remitting clinical course.
STATEMENT OF AUTHORSHIP
Category 1: a. Conception and design: R. K. Shin, L. J. Mejico, D. Boghen; b. Acquisition of data: R. K. Shin, L. J. Mejico, D. Boghen, A. Kawasaki, V. A. Purvin, M. L. Moster, B. R. Younge; c. Analysis and interpretation of data: R. K. Shin, L. J. Mejico, D. Boghen. Category 2: a. Drafting the manuscript: R. K. Shin, L. J. Mejico, D. Boghen; b. Revising it for intellectual content: R. K. Shin, L. J. Mejico, D. Boghen. Category 3: a. Final approval of the completed manuscript: R. K. Shin, L. J. Mejico, D. Boghen, A. Kawasaki, V. A. Purvin, M. L. Moster, B. R. Younge.
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