ABSTRACT
The pathology of Huntington's disease (HD) is characterized by diffuse brain atrophy, with the most substantial neuronal loss occurring in the caudate and putamen. Recent evidence suggests that there may be more widespread neuronal degeneration with significant involvement of extrastriate structures, including white matter. In this study of pre-symptomatic carriers of the HD genetic mutation, we have used diffusion tensor imaging to examine the integrity and organization of white matter in a group of individuals who previously demonstrated abnormalities in response to a functional magnetic resonance imaging paradigm. Our results indicate that, before the onset of manifest HD, there are regional decreases in fractional anisotropy, indicating early white matter disorganization.
Subject(s)
Brain/pathology , Diffusion Magnetic Resonance Imaging , Huntington Disease/pathology , Adult , Anisotropy , Atrophy/pathology , Caudate Nucleus/pathology , Female , Humans , Male , Nerve Degeneration/pathology , Putamen/pathologyABSTRACT
Huntington's Disease-like 2 (HDL2) is a progressive, autosomal dominant, neurodegenerative disorder with marked clinical and pathological similarities to Huntington's disease (HD). The causal mutation is a CTG/CAG expansion mutation on chromosome 16q24.3, in a variably spliced exon of junctophilin-3. The frequency of HDL2 was determined in nine independent series of patients referred for HD testing or selected for the presence of an HD-like phenotype in North America or Japan. The repeat length, ancestry, and age of onset of all North American HDL2 cases were determined. The results show that HDL2 is very rare, with a frequency of 0 to 15% among patients in the nine case series with an HD-like presentation who do not have the HD mutation. HDL2 is predominantly, and perhaps exclusively, found in individuals of African ancestry. Repeat expansions ranged from 44 to 57 triplets, with length instability in maternal transmission detected in a repeat of r2=0.29, p=0.0098). The results further support the evidence that the repeat expansion at the chromosome 16q24.3 locus is the direct cause of HDL2 and provide preliminary guidelines for the genetic testing of patients with an HD-like phenotype.
Subject(s)
Huntington Disease/genetics , Trinucleotide Repeat Expansion/genetics , Adult , Age of Onset , Female , Genotype , Humans , Huntington Disease/epidemiology , Japan/epidemiology , Male , Membrane Proteins/genetics , Middle Aged , North America/epidemiology , Pedigree , Repetitive Sequences, Nucleic AcidABSTRACT
Evidence suggests early structural brain changes in individuals with the Huntington's disease (HD) genetic mutation who are presymptomatic for the movement symptoms of the illness. The aim of this study was to investigate the presence of functional brain changes in this same population using functional magnetic resonance imaging. Subjects and matched controls underwent an functional magnetic resonance imaging "interference" protocol, a task known to be mediated in part by corticostriatal circuitry. In the setting of normal cognitive performance, presymptomatic HD subjects had significantly and specifically less activation in the left anterior cingulate cortex (BA 24, 32) compared with matched controls.
Subject(s)
Brain/physiopathology , Cognition/physiology , Functional Laterality/physiology , Huntington Disease/physiopathology , Adult , Analysis of Variance , Brain/pathology , Brain Mapping , Case-Control Studies , Cognition Disorders/physiopathology , Female , Humans , Huntington Disease/pathology , Magnetic Resonance Imaging/methods , Male , Middle Aged , Neuropsychological Tests , Reaction Time/physiology , Severity of Illness IndexABSTRACT
The authors performed a chart review to determine the frequency with which neurologists detect cognitive and psychiatric symptoms in patients with cerebellar degeneration. Psychopathology, including depression, personality change, cognitive impairment, anxiety, and psychosis was noted in 51% of 133 patients.
Subject(s)
Cognition Disorders/complications , Psychotic Disorders/complications , Spinocerebellar Degenerations/complications , Aged , Basal Ganglia/physiology , Case-Control Studies , Chi-Square Distribution , Comorbidity , Depression/physiopathology , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Psychiatric Status Rating ScalesABSTRACT
Subjects were followed in the Longitudinal Core Study of the Baltimore Huntington's Disease Center and given annual neurological, cognitive, and psychiatric examinations. Postmortem neuropathological grade was assigned using the system of Vonsattel and colleagues. We examined the correlations between the neuropathological grade and scores on the Quantified Neurological Examination (QNE) and its chorea and motor impairment subscales, the Mini-Mental State Examination (MMSE), the HD Activities of Daily Living (ADL) Scale, and a number of demographic variables (CAG number, age of onset, age at death, disease duration) in 100 subjects who had been examined within 1,000 days of death. All measures showed significant correlation with Vonsattel score except for chorea. The strongest effect was that of motor impairment score (r(2) = 0.351, p < 0.0001). In a stepwise correlation of clinical variables, motor impairment remained significant. The largest effect for a demographic variable was for age of onset (r(2) = 0.226, p < 0.0001) A partial correlation was significant between CAG number and Vonsattel grade, controlling for age at death or disease duration. Motor impairment appears to be a good clinical measure of neuronal cell loss, at least late in the course of HD and therefore may prove useful in observational and treatment studies.
Subject(s)
Huntington Disease/physiopathology , Risk Factors , Activities of Daily Living , Adolescent , Adult , Age of Onset , Aged , Aged, 80 and over , Chorea , Eye Movements/physiology , Female , Humans , Huntington Disease/diagnosis , Longitudinal Studies , Male , Middle Aged , Motor Activity , Motor Skills , Neurologic Examination , Neuropsychological Tests , Psychiatric Status Rating Scales , Trinucleotide RepeatsABSTRACT
OBJECTIVES: First, to identify what physical performance differences existed between a group of disabled individuals with chronic pain and a control group of pain-free individuals with comparable disabilities; and second, to test a psychosocial model designed to evaluate which psychosocial constructs were predictive of performance in disabled individuals with chronic pain. DESIGN: Case-comparison study. SETTING: Ambulatory university laboratory. PARTICIPANTS: A community sample of 62 individuals with lower limb amputations or paraplegia, 31 with chronic pain and 31 pain-free. INTERVENTION: Standardized lifting and wheel-turning tasks. MAIN OUTCOME MEASURES: Static strength, endurance, lifting speed, lateral and anterior-posterior sway, and multidimensional psychosocial measures. RESULTS Disabled individuals with chronic pain had decreased endurance for both the lifting (p <0.001) and the wheel-turning (p <0.05) tasks. A psychosocial model of physical performance also was evaluated. Using confirmatory factor analysis, 31 measures were used to validate 8 theoretical constructs: emotional functioning, pain intensity, pain cognitions, physical functioning, social functioning, task-specific self-efficacy, performance outcome, and performance style. Regression analyses indicated that more than 90% of the variance in performance was predicted by psychosocial factors, with self-efficacy, perceived emotional and physical functioning, pain intensity, and pain cognitions showing the highest associations. CONCLUSIONS: Chronic pain was found to significantly reduce the performance in individuals with lower limb amputations and paraplegia. A strong association was found between performance and psychosocial factors in disabled individuals with chronic pain. These findings extend the existing literature by validating that psychosocial models of chronic pain can be applied to the disabled population, with results similar to those of other chronic pain samples.
