Influence of GAA expansion size and disease duration on central nervous system impairment in Friedreich's ataxia: contribution to the understanding of the pathophysiology of the disease

Objective: To verify if GAA expansion size could account for the severity o f the central nervous system involvement in Friedreich's ataxia (FA). Methods: Retrospective study of 52 FA patients (mean age 26.9 +/- 12.1 year s; mean disease duration 10.6 +/- 7.6 years) homozygous for GAA expansion. Median nerve somatosensory evoked potentials (SSEPs) were available in 36 F A patients, upper limb motor evoked potentials (MEPs) to transcranial magne tic stimulation in 32, brainstem auditory evoked potentials (BAEPs) in 24, and visual evoked potentials (VEPs) in 34, N20, P100, MEP amplitude, SSEP a nd MEP central conduction time (CCT and CMCT), P100 latency and I-III and I -V interpeak latency, and a BAEP abnormality score were correlated with dis ease duration and GAA expansion size on the shorter (GAA1) and larger (GAA2 ) allele in each pair. Results: The GAA1 size inversely correlated with the N20 amplitude (r = -0. 49; P < 0.01). Disease duration directly correlated with CMCT (r = 0.57; P < 0.01) and BAEP score (r = 0.61; P < 0.01) and inversely with MEP (r = -0. 40; P < 0.05) and P100 amplitude (r = -0.39; P < 0.05). Conclusions: Our data suggest that central somatosensory pathway involvemen t in FA is mainly determined by GAA1 expansion size. Vice versa, degenerati on of pyramidal tracts, auditory and visual pathways seems to be a continui ng process during the life of FA patients. (C) 2000 Elsevier Science Irelan d Ltd. All rights reserved.