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 of the central nervous system involvement in Friedreich's ataxia (FA).


METHODS
Retrospective study of 52 FA patients (mean age 26.9+/-12.1 years; mean disease duration 10.6+/-7.6 years) homozygous for GAA expansion. Median nerve somatosensory evoked potentials (SSEPs) were available in 36 FA patients, upper limb motor evoked potentials (MEPs) to transcranial magnetic stimulation in 32, brainstem auditory evoked potentials (BAEPs) in 24, and visual evoked potentials (VEPs) in 34. N20, P100, MEP amplitude, SSEP and 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 disease 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 involvement in FA is mainly determined by GAA1 expansion size. Vice versa, degeneration of pyramidal tracts, auditory and visual pathways seems to be a continuing process during the life of FA patients.
Santoro
L
L
Department of Neurological Sciences, Servizio di Neurofisiopatologia, Università Federico II di Napoli, via Sergio Pansini 5, 80131, Napoli, Italy. lusantor@ds.unina.it
Perretti
A
A
Lanzillo
B
B
Coppola
G
G
De Joanna
G
G
Manganelli
F
F
Cocozza
S
S
De Michele
G
G
Filla
A
A
Caruso
G
G
D000293:Adolescent; D000328:Adult; D001921:Brain / Q000503:physiopathology*; D002648:Child; D005071:Evoked Potentials / Q000502:physiology*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D019054:Evoked Potentials, Motor / Q000502:physiology; D005073:Evoked Potentials, Somatosensory / Q000502:physiology; D005074:Evoked Potentials, Visual / Q000502:physiology; D005260:Female; D005621:Friedreich Ataxia / Q000235:genetics* / Q000503:physiopathology*; D006720:Homozygote; D006801:Humans; D008280:Magnetics; D008297:Male; D008475:Median Nerve / Q000503:physiopathology; D008875:Middle Aged; D012044:Regression Analysis; D012189:Retrospective Studies; D013997:Time Factors; D019680:Trinucleotide Repeat Expansion