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Subtle changes among presymptomatic carriers of the Huntington's disease gene
J Neurol Neurosurg Psychiatry 2000;69:773-779 ( December )Received 14 February 2000 and
in revised form 13 June 2000; Accepted 7 August 2000
OBJECTIVES
To compare the neurological and
psycho-metric characteristics of presymptomatic
gene carriers and non-gene carriers who are at risk for developing Huntington's
disease so as to characterise early signs of disease and to identify markers of neurological function that could be used to
assess the impact of experimental therapies on the progression of disease, even among those who are clinically
presymptomatic.
METHODS
A
sample of people at risk for Huntington's disease was genotyped and evaluated using subscales of the Wechsler adult intelligence
scale-revised (WAIS-R), a quantified neuro-logical rating scale, and computerised physio-logical measures including speed
of movement and reaction time.
RESULTS
Genotyping and clinical examination determined that 171
participants were
presymptomatic gene carriers (PSGCs) and 414 participants were non-gene carriers
(NGCs).
The
PSGCs performed significantly worse when compared with the NGCs on the digit symbol, picture arrangement, and arithmetic subscales
of the WAIS-R (p<0.02) and for the physiological measures: button tapping, auditory reaction time, visual reaction time
with decision, and movement time with and without decision (p<0.05).
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RESULTS continiued
Although no PSGCs had sufficient neuro-logical findings to warrant a diagnosis
of Huntington's
disease on clinical examination, the PSGCs had more frequent
possible or definite abnormality for oculo-motor function,
chorea, muscle stretch
reflexes, gait, and station stability, and rapid alternating movements (p0.02).
CONCLUSIONS
Among Huntington's disease gene carriers, subtle cognitive
and motor deficits precede the onset of sufficient neurological abnormality to warrant a clinical diagnosis of Huntington's
disease.
S C Kirkwooda, E Siemersb, M E Hodesa, P M Conneallya, J C Christiana, T Forouda a
Department of Medical and Molecular Genetics, Indiana University School of
Medicine, 975 West Walnut Street, Indianapolis,
Indiana 46202, USA,
b Eli Lilly and Company, Indianapolis, IN 46285, USA
Received
14 February 2000 and in revised form 13 June 2000; Accepted 7 August 2000
Source: J Neurol Neurosurg Psychiatry 2000;69:773-779 ( December ) Study |
