Rate of caudate atrophy in presymptomatic and symptomatic stages of Huntington's disease

Previous research by our group demonstrated a longitudinal change in caudate volume for symptomatic subjects with Huntington's disease (HD), and suggested that volume of the caudate may be a useful outcome measure for therapeutic studies in symptomatic patients. The current study was designed to determine whether longitudinal change in caudate atrophy could be documented in presymptomatic carriers of the HD gene mutation, and to compare rate of change in these subjects with rate of change in mildly and moderately affected symptomatic patients. We measured caudate volumes on serial magnetic resonance image scans from 30 patients at three stages of HD: 10 presymptomatic; 10 with mild symptoms, as indicated by scores on the Quantified Neurological Exam (QNE) ≤35; and 10 with moderate symptoms (QNE >45). The mean interscan interval was 36 months. When analyzed separately, both symptomatic groups and the presymptomatic group demonstrated a significant change in caudate volume over time. Amount of change over time did not differ significantly among the three groups. We conclude that change in caudate volume may be a useful outcome measure for assessing treatment effectiveness in both presymptomatic and symptomatic subjects.

[1]  R. Hichwa,et al.  PET scan investigations of Huntington's disease: Cerebral metabolic correlates of neurological features and functional decline , 1986, Annals of neurology.

[2]  S. Folstein,et al.  Putamen volume reduction on magnetic resonance imaging exceeds caudate changes in mild Huntington's disease , 1992, Annals of neurology.

[3]  K. Kieburtz,et al.  Assessment of coenzyme q10 tolerability in huntington's disease , 1996, Movement disorders : official journal of the Movement Disorder Society.

[4]  S. Fahn,et al.  Huntington disease , 1979, Neurology.

[5]  J. Brandt,et al.  Reduced basal ganglia volume associated with the gene for Huntington's disease in asymptomatic at‐risk persons , 1994, Neurology.

[6]  R. M. Stewart,et al.  Evoked potentials in Huntington's disease. A comparative and longitudinal study. , 1984, Archives of neurology.

[7]  Manish S. Shah,et al.  A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes , 1993, Cell.

[8]  G. Pearlson,et al.  Basal ganglia volume and proximity to onset in presymptomatic Huntington disease. , 1996, Archives of neurology.

[9]  J. Brandt,et al.  Trinucleotide repeat length and clinical progression in Huntington's disease , 1996, Neurology.

[10]  M. MacDonald,et al.  CAG repeat number governs the development rate of pathology in Huntington's disease , 1997, Annals of neurology.

[11]  Ira Shoulson,et al.  Huntington's disease in venezuela: 7 years of follow‐up on symptomatic and asymptomatic individuals , 1990, Movement disorders : official journal of the Movement Disorder Society.

[12]  Jane S. Paulsen,et al.  Unified Huntington's disease rating scale: Reliability and consistency , 1996, Movement disorders : official journal of the Movement Disorder Society.

[13]  E. Aylward,et al.  Huntington disease and the related disorder, dentatorubral-pallidoluysian atrophy (DRPLA). , 1997, Medicine.

[14]  J C Mazziotta,et al.  Serial changes of cerebral glucose metabolism and caudate size in persons at risk for Huntington's disease. , 1992, Archives of neurology.

[15]  C A Ross,et al.  Correlation between the onset age of Huntington's disease and length of the trinucleotide repeat in IT-15. , 1993, Human molecular genetics.

[16]  Terry L. Jernigan,et al.  Cerebral structure on MRI, part II: Specific changes in Alzheimer's and Huntington's diseases , 1991, Biological Psychiatry.

[17]  D. Eidelberg,et al.  [11C]Raclopride‐PET studies of the Huntington's disease rate of progression: Relevance of the trinucleotide repeat length , 1998, Annals of neurology.

[18]  S. Folstein,et al.  The diagnosis of Huntington's disease , 1986, Neurology.

[19]  R. Roos,et al.  Unified Huntington's disease rating scale: A follow up , 1998, Movement disorders : official journal of the Movement Disorder Society.

[20]  P Boesiger,et al.  Striatal glucose metabolism and dopamine D2 receptor binding in asymptomatic gene carriers and patients with Huntington's disease. , 1996, Brain : a journal of neurology.

[21]  S. Plumb,et al.  A controlled clinical trial of baclofen as protective therapy in early huntington's disease , 1989, Annals of neurology.

[22]  G. Pearlson,et al.  Longitudinal change in basal ganglia volume in patients with Huntington's disease , 1997, Neurology.

[23]  Lisfrancm..  On the Treatment of White Tumors of the Joints , 1835 .

[24]  R. Ferrante,et al.  Neuropathological Classification of Huntington's Disease , 1985, Journal of neuropathology and experimental neurology.

[25]  M. Hayden,et al.  Positron emission tomography in the early diagnosis of Huntington's disease , 1986, Neurology.

[26]  I. Shoulson,et al.  A prospective evaluation of cognitive decline in early Huntington's disease , 1995, Neurology.

[27]  I. Shoulson,et al.  Experimental therapeutics of neurodegenerative disorders: unmet needs. , 1998, Science.

[28]  R. Hichwa,et al.  Longitudinal neuropsychological and genetic linkage analysis of persons at risk for Huntington's disease. , 1995, Archives of neurology.

[29]  K. Kieburtz,et al.  Functional decline in Huntington's disease , 1995, Movement disorders : official journal of the Movement Disorder Society.

[30]  Jane S. Paulsen,et al.  Unified Huntington's disease rating scale: Reliability and consistency , 1996, Movement disorders : official journal of the Movement Disorder Society.

[31]  J. Mazziotta,et al.  Reduced cerebral glucose metabolism in asymptomatic subjects at risk for Huntington's disease. , 1987, The New England journal of medicine.

[32]  J. Brandt,et al.  Neuropsychological stability over two years in asymptomatic carriers of the Huntington's disease mutation. , 1996, Journal of neurology, neurosurgery, and psychiatry.

[33]  E. Aylward,et al.  Does CAG repeat number predict the rate of pathological changes in Huntington's disease? , 1998, Annals of neurology.

[34]  R J Leigh,et al.  The measurement of abnormal movement: methods developed for Huntington's disease. , 1983, Neurobehavioral toxicology and teratology.

[35]  M. Hayden,et al.  The combined use of positron emission tomography and DNA polymorphisms for preclinical detection of Huntington's disease , 1987, Neurology.