Progressive ataxia with oculo-palatal tremor and optic atrophy

Abstract

A 42-year-old man of Polish extraction presented with a four year history of slowly deteriorating reading difficulties and gait imbalance. There was no evidence for alcohol or recreational substance abuse. Family history was unremarkable. On examination he had tandem gait ataxia. Power was normal and with no atrophies. Deep tendon reflexes were pronounced on the left with ipsilaterally extensor plantar response. He had upper limb past pointing, pronounced on the left. Visual acuity was 20/60 on the right and 20/80 on the left. Colour vision (Ishihara plates): 13/15 on the right and 10/15 on the left. Humphrey 10:2 perimetry showed reduced sensitivity paracentrally in both eyes. Retinae appeared normal, however both optic discs showed temporal wedge-shaped pallor (Fig. 1). Examination of extraocular movements was supported by binocular 3D video oculography (video 1). Pendular torsional nystagmus in primary gaze was detected, partly attenuated on left gaze. The nystagmus had two components, a baseline, low amplitude (1 –2 ), symmetrical, pendular, torsional oscillation (1.7–2 Hz), and an irregular larger amplitude (2 –5 ) nystagmus beating clockwise from the observer’s point of view. Both nystagmus components were pronounced in the right eye. The torsional faster component included a large upwards component in the right eye (‘left pendular hemiseesaw nystagmus’) [1] (Fig. 1). Non-periodic tremor (2 Hz) of the soft palate and posterior pharyngeal wall muscles was evident (video 2). Optical coherence tomography of the peripapillary retinal nerve fibre layer confirmed bilateral segmental optic atrophy (Fig. 1). Full-field and multifocal electroretinograms were normal. Amplitudes of pattern reversal visual evoked potentials were bilaterally borderline reduced. Haematology and biochemistry indices were normal as were vitamin B12, folic acid, thyroid function, syphilis and HIV 1/2 serology, and screening for onconeuronal and other auto-antibodies. Cerebrospinal fluid analysis was normal. Full GFAP gene sequencing failed to support the presence of Alexander’s disease [2]. Search for spinocerebellar ataxia expansions and/or duplications 1–3, 6, 7, 12 and 20 was negative [3, 4] as were searches for mitochondrial mutations associated with (1) Leber’s hereditary optic atrophy [5], (2) mitochondrial encephalomyopathy,lactic acidosis and stroke-like episodes, (3) myoclonic Electronic supplementary material The online version of this article (doi:10.1007/s00415-013-7136-3) contains supplementary material, which is available to authorized users.