Progression markers of Spinocerebellar ataxia 2. A twenty years neurophysiological follow up study

Nerve conduction is profoundly affected in Spinocerebellar ataxia 2 (SCA2) even before the onset of the disease, but there is no information regarding its progression to the final stage of SCA2. In order to study the progression patterns of nerve conduction abnormalities in SCA2 we performed a prospective follow up evaluation of sensory and motor conduction in 21 SCA2 mutation carriers-initially presymptomatics- and 19 non-SCA2 mutation carriers during 20years. The earliest electrophysiological alterations were the reduction of sensory amplitudes in median and sural nerves, which could be found 8 to 5years prior disease onset and in the last 4years of the preclinical stage respectively. These abnormalities were followed by the increase of sensory latencies and decrease of conduction velocities. Sensory amplitudes progressively decreased during the follow-up clinical stage, rendering almost all patients with abnormal amplitudes and lack of sensory potentials, with faster progression rates in patients with larger CAG repeat lengths. Peripheral motor nerves showed the later involvement. These findings were used to define three distinct stages that describe the progression of the peripheral neuropathy. We suggest that sensory amplitudes could be useful biomarkers to assess the progression of peripheral nerve involvement and therefore to evaluate future clinical trials of therapeutic agents.