Vestibulo-ocular arreflexia in families with spinocerebellar ataxia type 3 (Machado-Joseph disease).(Paper)

J Neurol Neurosurg Psychiatry 2003;74:1403-1406

Objective: To identify the presence of vestibulo-ocular arreflexia in patients with Machado-Joseph disease (MJD), which can easily be diagnosed at the bedside.

Methods: Seven patients with MJD from five unrelated families and 11 patients with sporadic or hereditary cerebellar ataxia other than MJD underwent a detailed neuro-otological and oculomotor examination. Six MJD and five non-MJD patients also underwent electro-oculographic recordings and caloric tests.

Results: Gaze evoked nystagmus, smooth pursuit, and saccade abnormalities were found in both MJD and non-MJD patients. However, in all seven MJD patients but in none of the non-MJD patients, sudden passively induced head thrust to both sides elicited pathological corrective catch-up saccades, indicating bilateral loss of the horizontal vestibulo-ocular reflex. This was further confirmed in six MJD patients who had absent vestibular response to both a standard caloric test and ice water ear irrigation. Nystagmus was induced by standard caloric irrigation in all non-MJD patients examined. There was no correlation between the loss of vestibular function and the severity of cerebellar impairment.

Conclusions: The presence of vestibulo-ocular arreflexia, as measured by the head thrust test in a patient with dominant cerebellar ataxia, strongly suggests the diagnosis of MJD.

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Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD), is the most common form of autosomal dominant cerebellar ataxia. (1 2) Although all forms of hereditary spinocerebellar ataxia are the result of multisystem degeneration with widespread neurological impairment, there is sparse information on a specific involvement of the vestibular system. Despite the fact that several reports concerning vestibular hypofunction in patients with MJD were published both before and after genetic testing became available, the concept of vestibular dysfunction in MJD is not widely accepted. (3-5)

In Israel we have described a Yemenite Jewish genetic isolate of MJD which was characterised by a relatively large number of homozygotes for the CAG trinucleotide repeat expansion at the MJD1 gene. (6 7)

The present report describes vestibulo-ocular arreflexia in patients with MJD, which can easily be diagnosed at the bedside and used in planning genetic studies in patients with autosomal dominant cerebellar ataxia.

METHODS

Seven patients with MJD from five unrelated families, seven patients with autosomal dominant cerebellar ataxia other than MJD, and four patients with sporadic forms of cerebellar ataxia agreed to participate in the study (tables 1 and 2). All patients with genetically proven MJD were of Jewish-Yemenite extraction. The non-MJD group consisted of three patients with familial episodic ataxia type 2 (EA-2), two with SCA6, two with undiagnosed autosomal dominant cerebellar ataxia, and four with sporadic cerebellar ataxia. In the last six patients, SCA1, 3, 6, and 7, dentatorubropallidoluysian atrophy (DRPLA), vitamin E deficiency, and coeliac disease were ruled out.

All subjects (MJD and non-MJD) had a negative past history for vertigo or hearing impairment. Only one MJD patient reported transient oscillopsia during locomotion or riding in a car. Five MJD patients underwent pure tone audiometry, which was normal.

Following a complete neurological examination, each patient had a detailed oculomotor and neuro-otological examination according to Zee and Fletcher. (8) This included:

* eye movement testing (alignment, range of motion, vergence, saccades, smooth pursuit, optokinetic nystagmus, and visual cancellation of the vestibulo-ocular reflex (VOR);

* evaluation …