Spanish family with Machado-Joseph disease: neurophysiological features and neuropathy study

Abstract We have carried out electrophysiological studies and sural nerve biopsy evaluation in a Spanish family with genetically proven Machado-Joseph disease (SCA3/MJD) phenotype III. Two symptomatic and other two asymptomatic members of the family were clinically examined. Electrophysiological evaluation included multimodal evoked potentials, quantitative electromyography and nerve conduction studies, and central motor conduction time. We also report neuropathological findings in the sural nerve biopsy in the proband. Analysis of the SCA3/MJD CAG trinucleotide repeat at the ataxin 3 gene in the DNA of the proband and one of his daughters demonstrated an expanded allele of 63 CAG repeat units. Ataxic pursuit was primary disturbed in MJD, followed by gaze evoked nystagmus, hypermetric saccades and glissades. Limitation of vertical and horizontal gaze, impaired sinusoidal vestibulo-ocular reflex and vestibulo-ocular reflex-fixation-suppression, and active and passive optokinetic nistagmus loss appeared at later stages. Evoked potential studies showed multimodal abnormalities. Electrophysiological and sural nerve biopsy findings correspond well to a pattern of both anterior horn and root ganglion cell distal dominant degeneration. Central motor conduction time was normal in our patients up to advanced stages of the disease. Electrophysiological and neuropathological studies suggested widespread peripheral and central affection in MJD. Repeated application of electrophysiological techniques may prove useful for monitoring disease progress.