Topiramate Effect in Opsoclonus-Myoclonus-Ataxia Syndrome

A 34-year-old woman with no comorbidities developed severe truncal ataxia and opsoclonus progressively over 4 days. The patient was admitted 20 days after onset of symptoms. During hospitalization, she was extensively investigated for the etiology of opsoclonus-myoclonus-ataxia syndrome (OMS). All ancillary tests performed gave normal results, including cerebrospinal fluid examination; serology for infectious diseases and collagenosis; brain and spine magnetic resonance imaging; thoracic, abdominal, and pelvic computerized tomography; and screening for gynecological neoplasias. Topiramate treatment was initiated at a starting dose of 50 mg/d and was titrated up to 150 mg/d over 10 days. During this period, the patient had a remarkable improvement of symptoms (video). After a few days, the topiramate dose was gradually decreased to 50 mg/d. However, after 1 week, ataxia and the opsoclonus clearly worsened. After reestablishing the medication dose to 150 mg/d, symptoms improved again.

Opsoclonus-myoclonus-ataxia syndrome is a rare disorder that affects mainly children and is characterized by a combination of abnormal eye movements, limb myoclonia, and cerebellar ataxia. Opsoclonus is defined as involuntary, conjugate, arrhythmic, multidirectional, high-amplitude saccades that persist during sleep and are exacerbated by visual fixation.¹ Opsoclonus should be distinguished from ocular flutter.² Despite many features shared by both conditions, ocular flutter occurs only in the horizontal plane, is continuous, has a small amplitude, and lasts for a few beats.^{2 - 3}

Flutter and opsoclonus may be secondary to paraneoplastic disease. About 50% of children with OMS have underlying neuroblastoma. Breast, ovarian, and lung cancer are also associated with this syndrome.^{1 - 2} If results of an investigation for neoplasia are negative, other etiologies for OMS should be considered, including multiple sclerosis, toxic metabolic states, and infectious diseases (poliomyelitis, salmonella, and Coxsackie virus).^{1 - 2 ,4}

The exact mechanism underlying OMS is unknown, but evidence points to the cerebellum as a key structure.¹ A loss of inhibitory γ-aminobutyric acid–mediated control leading to disinhibition of the fastigial nucleus in the cerebellum is likely.¹

Topiramate is an antiepileptic drug whose exact mechanism of action is not completely understood. Among the hypothesized mechanisms, inhibition of glutamate-mediated neurotransmission and increment of the γ-aminobutyric acid–mediated current are especially relevant. These actions stabilize hyperexcited neuronal membranes and thus augment GABAergic activity. This may inhibit the cerebellar circuits involved in OMS physiopathology, thereby improving the symptons.⁴ Symptomatic control with topiramate may be an effective, new alternative for treating OMS, as described herein.