Journal of Neuro-Ophthalmology, September 2013, Volume 33, Issue 3

Acquired Oculomotor Nerve Paresis with Cyclic Spasms in a Young Woman, a Rare Subtype of Neuromyotonia

To report an unusual case of cyclic oculomotor nerve paresis and spasms, which developed 5 years following brain radiotherapy for cerebellar medulloblastoma. Observational case report. The cyclic oculomotor nerve paresis and spasms resolved in our patient when treated with carbamazepine. However, because of severe photophobia and tearing, carbamazepine had to be discontinued leading to reappearance of the eye movement disorder. Cyclic oculomotor nerve paresis and spasms appear to be a delayed effect of radiotherapy and respond to carbamazepine therapy. It may be a rare form of ocular neuromyotonia.

Acquired Oculomotor Nerve Paresis with Cyclic Spasms in a Young Woman, a Rare Subtype of Neuromyotonia Avi Gadoth, MD, Svetlana Kipervasser, MD, Amos D. Korczyn, MD, Miri Y. Neufeld, MD, Anat Kesler, MD Background: To report an unusual case of cyclic oculomotor nerve paresis and spasms, which developed 5 years following brain radiotherapy for cerebellar medulloblastoma. Methods: Observational case report. Results: The cyclic oculomotor nerve paresis and spasms resolved in our patient when treated with carbamazepine. However, because of severe photophobia and tearing, carbamazepine had to be discontinued leading to reappear-ance of the eye movement disorder. Conclusion: Cyclic oculomotor nerve paresis and spasms appear to be a delayed effect of radiotherapy and respond to carbamazepine therapy. It may be a rare form of ocular neuromyotonia. Journal of Neuro-Ophthalmology 2013;33:247-248 doi: 10.1097/WNO.0b013e318294a2ae © 2013 by North American Neuro-Ophthalmology Society Ocular neuromyotonia (ONM) is an acquired disorder characterized by brief episodic contractions of muscles supplied by the oculomotor, trochlear, or abducens nerves resulting in paroxysmal strabismus and diplopia (1-5). It usually is associated with a history of previous radiation therapy to the parasellar region (3-6). Cyclic oculomotor paresis and spasms (COPS) is a rare phenomenon, that is, usually congenital (7). Miller and Lee (8) described 2 patients with COPS, appearing years following irradiation of the skull base. They proposed that acquired COPS and ONM may be related phenomena with similar underlying mechanisms. We describe a young woman with acquired oculomotor paresis with cyclic spasms following brain radiotherapy and treated with carbamazepine. CASE REPORT A 34-year-old woman underwent resection of posterior fossa medulloblastoma followed by radiotherapy and chemother-apy. Five years later, she developed intermittent episodes of vertical and horizontal diplopia associated with intermittent incomplete closure of the left eyelid. Neuro-ophthalmologic examination, including extraocular movements, was normal except for episodes that cycled every 2-3 minutes of partial left oculomotor spasm alternating with paresis. During the paretic phase, the patient had left hypotropia and moderate limitation in adduction of the left eye. Neurological testing was otherwise normal except for mild ataxia. Brain magnetic resonance imaging (MRI) with contrast showed no evidence of recurrent tumor and ictal and prolonged interictal electroencephalogram recordings were normal. Treatment with carbamazepine 400 mg daily completely relieved the eye movement disorder, but 2 years later, the patient developed severe photophobia and tearing. Carbamazepine was discontinued and the photophobia resolved but the abnormal ocular movements reappeared. The episodes of involuntary eye movements leading to vertical and horizontal diplopia consisted of cyclic oculomotor spasms and paresis of the left eye. They lasted for 1-2 minutes, recurring every few hours spontaneously or provoked by focusing on an object (see Supplemental Digital Content, Video 1, http://links.lww.com/WNO/A74 [informed consent was sought and granted by the patient for the filming and publishing of the related video]). On occasion, there were episodes of forced adduction of the left eye with reduced eyelid opening (Fig. 1). Infrequent intermittent limitation of abduction of the left eye was observed (see Supplemental Digital Content, Video 2, http://links.lww.com/WNO/A75). Department of Neurology (AG, SK, ADK, MYN), Neuro-Ophthalmology Unit (AK), and Department of Ophthalmology (AK), Tel Aviv Sourasky Medical Center; and Sackler School of Medicine (AG, SK, ADK, MYN, AK), Tel Aviv University, Tel Aviv, Israel. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the full text and PDF versions of this article on the journal's Web site (www. jneuro-ophthalmology.com). The authors report no conflicts of interest. Address correspondence to Avi Gadoth, MD, Department of Neu-rology, Tel Aviv Medical Center, 6 Weizmann Street, Tel Aviv 64239, Israel; E-mail: [e-mail] Gadoth et al: J Neuro-Ophthalmol 2013; 33: 247-248 247 Original Contribution Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Therapeutic trials with oxcarbazepine, phenytoin, and lamotrigine failed to halt the abnormal eye movements. Carbamazepine was restarted with marked improvement but with the return of photophobia. DISCUSSION Almost all reported cases of COPS have occurred in children or adults with a longstanding history of ocular motor dysfunction (7). Adult patients with acquired COPS typically occur following an acquired oculomotor nerve palsy without a history of previous brain radiotherapy. The clinical profile of our patients fits closely to that re-ported by Miller and Lee (8). They described 2 patients who developed COPS following radiation for pituitary tumor and parasellar meningioma. Like our patient, they did not have an oculomotor nerve palsy prior to onset of COPS. One of their patients failed to improve on carbama-zepine, whereas the other declined treatment. Given the spontaneous onset of the cyclic oculomotor disorder, and prior exposure to radiation therapy to the skull base, Miller and Lee postulated that while COPS differed from ONM, they likely shared similar pathogenic mechanism. Although the etiology of COPS is unknown, Loewenfeld and Thompson (7) believed that the disorder is caused by damage to the intracranial portion of the oculomotor nerve, with retrograde degeneration of oculomotor neurons. This leads to unstable cell membranes resulting from segmental demyelination or microangiopathy (3), and the injured nerve generates spontaneous impulses, leading to involuntary con-traction of the muscles innervated by the oculomotor nerve (4). Our case appears unique. The clinical picture resembles COPS, in that the spasms were followed by a paretic phase, but between episodes, eye movements were normal. As in ONM, the episodes could be provoked by change in gaze while focusing on an object. The clinical findings in our patient combining COPS with neuromyotonic characteristics and following radiation therapy makes it likely that both eye movement disorders share similar underlying mechanisms. Although not a reported side effect in the literature, 12 cases of photophobia associated with carbamazepine are recorded in the data file of Novartis (Amos D. Korczyn, MD, personal communication, 2012). The fact that photophobia dis-appeared after treatment was halted and reemerged follow-ing rechallenge supports the conclusion that photophobia is a rare side effect of carbamazepine. REFERENCES 1. Barroso L, Hoyt WF. Episodic exotropia from lateral rectus neuromyotonia-appearance and remission after radiation therapy for a thalamic glioma. J Pediatr Ophthalmol Strabismus. 1993;30:56-57. 2. Newman SA. Gaze-induced strabismus. Surv Ophthalmol. 1993;38:303-309. 3. Hadjikoutis S, Morgan JE, Wild JM, Smith PEM. Ocular complications of neurological therapy. Eur J Neurol. 2005;12:499-507. 4. Gordon TP. Putting ONM in context. J Neuroophthalmol. 2006;26:241-243. 5. Frohman EM, Zee DS. Ocular neuromyotoma: clinical features, physiological mechanisms, and response to therapy. Ann Neurol. 1995;37:620-626. 6. Lessell S, Lessell IM, Rizzo JF. ONM after radiation therapy. Am J Ophthalmol. 1986;102:766-770. 7. Loewenfeld IE, Thompson HST. Oculomotor paresis with cyclic spasms. A critical review of the literature and a new case. Surv Ophthalmol. 1975;20:81-124. 8. Miller NR, Lee AG. Adult-onset acquired oculomotor nerve paresis with cyclic spasms: relationship to ONM. Am J Ophthalmol. 2004;137:70-76. FIG. 1. During a period of spasm, there is adduction of the left eye and narrowing of the palpebral fissure. 248 Gadoth et al: J Neuro-Ophthalmol 2013; 33: 247-248 Original Contribution Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.