Neurophysiological Studies and Non-Motor Symptoms Prior to Ataxia in a Patient with Machado-Joseph Disease: Trying to Understand the Natural History of Brain Degeneration

Spinocerebellar ataxia type 3 or Machado-Joseph disease is the most common spinocerebellar ataxia. in this neurological disease, anatomical, physiological, clinical, and functional neuroimaging demonstrate a degenerative process besides the cerebellum. We performed neurophysiological and neuroimaging studies-polysomnography, transcranial sonography, vestibular-evoked myogenic potential, single-photon emission computed tomography (SPECT) with Tc-99m-TRODAT-1, and a formal neuropsychological evaluation in a patient with sleep complaints and positive testing for Machado-Joseph disease, without cerebellar atrophy, ataxia, or cognitive complaints. Polysomnography disclosed paradoxical high amplitude of submental muscle, characterizing REM sleep without atonia phenomenon. Transcranial sonography showed hyperechogenicity of the substantia nigra. There was an absence of vestibular-evoked myogenic potentials on both sides in the patient under study, in opposite to 20 healthy subjects. Brain imaging SPECT with Tc-99m-TRODAT-1 demonstrated a significant lower DAT density than the average observed in six healthy controls. Electroneuromyography was normal. Neuropsychological evaluation demonstrated visuospatial and memory deficits. Impairment of midbrain cholinergic and pontine noradrenergic systems, dysfunction of the pre-synaptic nigrostriatal system, changes in echogenicity of the substantia nigra, and damage to vestibulo-cervical pathways are supposed to occur previous to cerebellar involvement in Machado-Joseph disease.Universidade Federal de São Paulo, Dept Neurol, Ataxia Unit, São Paulo, BrazilHosp Israelita Albert Einstein, São Paulo, BrazilUniv São Paulo, Dept Clin Neurosurg, São Paulo, BrazilUniv Estadual Ceara, Ctr Hlth Sci, Fortaleza, Ceara, BrazilUniversidade Federal de São Paulo, Dept Psychiat, São Paulo, BrazilUniversidade Federal de São Paulo, Behav Neurol Sect, Dept Neurol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Neurol, Ataxia Unit, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychiat, São Paulo, BrazilUniversidade Federal de São Paulo, Behav Neurol Sect, Dept Neurol, São Paulo, BrazilWeb of Scienc