Downward vertical gaze palsy as a prominent manifestation of episodic ataxia type 2: a case report.

OBJECTIVE: Episodic ataxia type 2 (EA2) is an inherited autosomal dominant disorder characterized by intermittent ataxia, nausea, vomiting, dysarthria, or nystagmus. We report a case of EA2, which downward gaze palsy exists as a common sign in all her attacks. Responsiveness of EA2 to acetazolamide was observed in this patient.

Introduction

Intermittent and recurrent ataxias are described in several vestibular, metabolic, vascular, and genetic disorders (1). Episodic ataxias (EAs) are characterized by recurrent episodes of cerebellar ataxia, vertigo, dysarthria, and nystagmus, starting in childhood and lasting for minutes or hours, with otherwise normal brain functions (2). Data is not available on the exact incidence of EAs, but it seems to occur in 3 to 5 people per 100,000 in the population (3). Nowadays there are seven recognized EA syndromes (numbered 1 to 7). These disorders share some common features: all are channelopathies with autosomal-dominant inheritance pattern and are responsive to acetazolamide (2). EA1 and EA2 are clinically well described, while the others are exceptionally rare (3). Both EA1 and EA2 are the result of ion channel mutations. Mutations in a potassium channel gene (KCNA1) located on chromosome 12p13 underlie EA1, and in a voltage-dependent calcium channel gene (CACNA1A) located on chromosome 19p13 can lead to EA2 (4). EA1 is characterized by brief episodes of ataxia lasting seconds to minutes, with onset in early childhood and often induced by startle or exercise, emotional stress, sudden change in posture, and by the continuous interictal myokymia (5,6). EA2, spinocerebellar ataxia type 6 (SCA6), and familial hemiplegic migraine all represent allelic mutations in the same calcium channel gene on chromosome 19p13 (7). EA2 is the most common of all episodic ataxias. The attacks are often associated with nausea, vomiting, dysarthria, or nystagmus, and last several hours to days. The frequency of these paroxysmal events varies from daily to once a year. The attacks are triggered by physical exertion, stress, or nonspecific febrile illness. In contrast with EA1, the attacks are not related to sudden movement. Approximately 50-70% of all patients with EA2 are responsive to treatment with acetazolamide, concerning both the frequency and the severity of the attacks (8). Sodium valproate may be a necessary adjunct to acetazolamide (9).

Case presentation

A 6-year-old girl was presented with a 3 year-long history of episodic instability, upward gaze, vomiting, vertigo, and cerebellar signs (dysmetria and dysarthric speech). She was developmentally normal. Her parents were not consanguine. Her family history showed no cases of similar illness. The first attack had begun at 21 months of age with sudden onset of upward gaze and nausea after a febrile disease, which led to hospitalization with suspicious diagnosis of seizure and lasted for two days. Thereafter, her mother mentioned the recurrence of similar attacks after every febrile disease, which did not respond to usual symptomatic treatments.

Downward gaze palsy existed as a common sign in all her attacks. The attacks occured approximately once a month and between them, she was completely normal. Her symptoms were relieved during sleep, and were not related to bath, foods and exercise. Blood cell counts, urinalysis, blood and urine amino acid chromatography, liver and renal function tests, blood gases, serum biochemistry and electrolytes all were in normal ranges. Auditory-evoked potentials, cerebrospinal fluid (CSF) studies, electroencephalogram (EEG), and brain magnetic resonance imaging (MRI) were also normal. The patient was hospitalized several times with various diagnoses, such as inherited metabolic disorder, basilar migraine, and epilepsy, and was treated with several drugs that were not effective. Then, suspicious diagnosis of EA2 was made and acetazolamide was prescribed. The frequency and severity of her symptoms decreased after receiving acetazolamide. Approximately 2 months after the last treatment (acetazolamide 250 mg twice a day orally), the patient’s attacks were completely resolved. At present she is a 7-year old excellent student and goes to school regularly.