Studies On Clinical And Electrophysiological Characteristics Of Spinocerebellar Ataxia Type3in A Pedigree

Objective: To investigate genetic lineages， clinical and electrophysiologicalcharacteristics of spinocerebellar ataxia type3(SCA3) in a pedigree.Methods: We inspected the genetic， neuroimaging and electrophysiologicalcharacteristics of11individuals belonging to a suspected SCA3pedigree in Fujian，andanalyzed clinical and electrophysiological characteristics of SCA3combining withliterature.Results：1. In the11members of the pedigree，the genetic tests of8individualsshowed that the CAG trinucleotide repeat times were beyond the normal range：5ofthem were diagnosed as SCA3patients， the repeated times of CAG were72.0±2.0(mean±SD；range70～75)；the other3individuals without clinical symptomswere asymptomatic patients and they were too young to onset the disease，therepeated times of CAG were71.0±1.0(mean±SD；range70～72). In the other3members，the CAG lengths were normal.2. Among22numbers of4generations in the pedigree had9patients，maleand female were affected，and SCA3had the feature of genetic anticipation.The age atonset of the disease was41.0±2.9years，with the most frequent symptoms beingprogressive ataxia，including gait ataxia，action clumsiness(100%). SCA3alsoaccompanied by involvement of the upper and lower motor neuron systems：the uppermotor involvement included positive pathological symptoms(100%)，active tendinousreflex(80%)，muscle tension(60%)；and the lower motor involvement were muscleatrophy(80%)， muscle weakness(40%). The International Collaboration AtaxiaAssessment Scale of World Federation of Mental Derangement(ICARS) scroes werein the range of32～83，The higher the ICARS score was，the more severe clinicalsymptoms the patients would get.3. Brain MRI showed remarkable atrophy on cerebellum and brain stem inSCA3patients.While asymptomatic patients had normal neuroimaging manifestations.4.SCA3showed multimodal abnormalities in somatosensory pathway、auditory pathway and visual pathway. Evoked potential studies indicated bothperipheral and central abnormalities. Somatosensory evoked potentials (SSEP) wereabnormal at a very early stage of diease. Peripheral nerve conduction studies(NCSs)presented axonal sensory-motor polyneuropathy and the sensory nerve fibers weremore involved. Nerve conduction velocities were normal.Electromyography(EMG）suggested a neurogenic affection. we also found that EMG can put up widespreadfibrillations and fasciculations in patients with obvious amyotrophy， and it’scompatible with motor neuron disease(MND).Conclusions:1.We speculate that the diease in the present pedigree is SCA3accompanied by involvement of the motor neuron systems(MNS).2. SCA3has high penetrance and there is a marked difference betweenpatients and normal person in the CAG trinucleotide repeat times.The detection of theCAG trinucleotide repeat times can provide an effective way for the genetic andasymptomatie diagnosis．3.Electrophysiological tests of SCA3have certain characteristic patterns：the evoked potentials of SCA3provide evidence of widespread central and peripheralaffection；SSEP may be an early electrophysiological marker of the disease and findabnormalities before the advent of clinical symptoms； NCSs present axonalsensory-motor polyneuropathy； EMG studies show signs of neurogenic changes.