Ideomotor apraxia in Huntington's disease.

The pattern of movement errors in ideomotor apraxia suggests an abnormality in selection and sequencing of component movements. Individuals with Huntington's disease were evaluated prospectively for the presence of apraxia, and aspects of motor and cognitive function were correlated with apraxic errors. Based on a conservative apraxia rating, ideomotor apraxia occurred in three (33%) of nine patients with a mean duration of disease of 10.4 years. Only two (22%) individuals made no apraxic errors, however, and the group as a whole made apraxic errors in 26% of movements. Apraxia was associated with errors in imitation of nonsymbolic movements but not with errors in recognition of gestures. It correlated significantly with duration of disease and with progressive abnormalities of posture but not with other individual aspects of elementary motor or cognitive function. These associations indicate that apraxia in Huntington's disease may be due primarily to involvement of subcortical motor structures rather than cerebral cortex.     

Diffusion-weighted imaging in Huntington's disease.

Huntington's disease (HD) is an autosomal dominant progressive neurodegenerative disorder that results from an expanded trinucleotide (CAG) repeat on the huntingtin gene. Neurodegeneration in HD affects most prominently the basal ganglia. Therefore, diffusivity was obtained in the basal ganglia and thalamus of 29 patients with early HD and 27 healthy volunteers by means of the trace of the diffusion tensor (Trace(D)). Putaminal, caudate, pallidal, and thalamic Trace(D) values were increased in patients with HD compared with controls. Increased diffusivity in the putamen and caudate nucleus correlated with global functional impairment, CAG repeat length, as well as bicaudate ratio. Diffusion-weighted imaging appears to be a promising surrogate marker for disease severity in HD. Sensitivity to change remains to be established longitudinally.     

Immunological status in Huntington's disease.

The immunological status of patients with Huntington's disease was studied and compared with that of an age-matched control group. No remarkable abnormalities in lymphocyte subpopulations were observed. The percentage of B cells, CD4+, CD8+, DR+ cells and stimulated cells bearing Tac receptors remained unchanged. The proliferative response to mitogens and the production of interleukin-1 (Il-1) were decreased, whereas the IgG level was increased. It is possible that changes in the levels of neurotransmitters affect the immunological function in basal ganglia disease.     

Intention myoclonus in Huntington's disease.

A patient is described with severe intention myoclonus which was made worse by treatment with L-Dopa and improved by clonazepam. Family history and examination of several siblings suggested the diagnosis of Huntington's disease. Subsequent to improvement of the myoclonus the patient appeared to have the rigid form of Huntington's disease. This case represents a unique expression for an otherwise well defined genetic abnormality. Stimulus activated myoclonus in a common feature of a number of disorders of the nervous system. Intention, or action myoclonus has been the subject of increasing interest because of its association with the syndrome of post-anoxic encephalopathy (1), although it may occur with other disorders as well. Many abnormal movements have been reported in Huntington's disease, but myoclonus is a relatively uncommon feature of this disorder and to our knowledge intention myoclonus has not been reported as a major symptom. We recently have evaluated a patient with disabling intention myoclonus and examined several members of his family who have typical Huntington's disease. We therefore report this case, a unique presentation of an otherwise well described movement disturbance.     

Sodium valproate in Huntington's disease.

The authors assessed the effect of sodium valproate, which is thought to elevate brain gamma-aminobutyric acid (GABA) levels, in the treatment of Huntington's disease by an objective ultrasound method in three patients with Huntington's disease. Despite plasma levels ranging from 47.0 to 140.8 microgram/ml (mean, 104.7), sodium valproate had no beneficial effect on involuntary movements. The authors stress the importance of activation to achieve a standard level of arousal in the assessment of involuntary movements.     

Obsessive-compulsive disorder in Huntington's disease.

Two patients with Huntington's disease (HD) and obsessive-compulsive disorder (OCD) are reported. The OCD was manifested by repetitive, stereotyped, complex, egodystonic behaviors that were disabling. These cases and other neurological syndromes with OCD (Gilles de la Tourette syndrome, neuroacanthocytosis, postencephalitic parkinsonism, caudate infarction, carbon monoxide poisoning, manganese intoxication, anoxia, progressive supranuclear palsy, Sydenham's chorea, and frontal lobe lesions) indicate that the frontal lobe, caudate nucleus, and globus pallidus are members of a complex circuit that plays a key role in mediating the symptoms of OCD. Evidence of excitatory subcortical output to cortex is shared by many neurological disorders manifesting OCD.     

Visuospatial cognition in Huntington's disease.

The notion of specificity of visuospatial dysfunction in Huntington's disease (HD) was evaluated in a sample of afflicted patients as a function of symptom duration, age at onset, and overall dementia severity. Factor analytic procedures indicated that overall visuospatial processing capacity (factor 1) as well as the ability for spatial manipulation (factor 3) was markedly affected in HD patients. In contrast, consistency of spatial judgment (factor 2) appeared to remain relatively intact in these patients. Age at onset seemed to have no relationship with any of these variables, whereas dementia severity demonstrated a significant relationship with overall visuospatial processing capacity. Most importantly, duration of symptoms was significantly associated with the declining ability to mentally perform spatial manipulations. The observation of circumscribed visuospatial impairment in HD patients may have important consequences for the further understanding of the neurobehavioral consequences of this disorder.     

Huntington's disease and minocycline.

A reply to this letter has been published in Movement Disorders Mov Disord (2005) 20 (4) 511 .     

Cortical glucose metabolism in Huntington's disease.

We measured cortical glucose metabolism with positron emission tomography in 39 patients with Huntington's disease (HD) and in 34 controls. In the 23 patients with symptoms for less than 5 years, there was a 15% decrease in metabolism in frontal and inferior parietal cortex. In 16 patients with symptoms for more than 5 years, all cortical areas (except temporal) were significantly involved, with metabolic rates 25 to 30% below those of controls. These data indicate the presence of a diffuse abnormality of cortical function with early involvement of frontal lobes in HD, suggesting that the clinical manifestations may not be related solely to basal ganglia pathology, even in early disease.     

Risky decision making in Huntington's disease.

In the clinical setting, Huntington's disease is associated with problems in judgment and decision making, however, the extent of these problems and their association with clinical characteristics have not been assessed. Recently, a laboratory-based simulated gambling task has been used to quantify similar decision-making deficits in ventromedial frontal lobe damaged participants. We hypothesized that participants with Huntington's disease (HD) would show deficits on this gambling task. For this study, 14 HD participants were asked to make 100 selections from four decks of cards with varied payoffs in order to maximize winnings of play money. They were compared to 22 participants with Parkinson's disease (PD) and 33 healthy controls. After an initial period in which participants had to learn contingencies of the decks, the HD group made fewer advantageous selections than the PD and control groups. In HD, the number of advantageous selections in the gambling task was correlated with measures of memory and conceptualization but not disinhibition. Thus, people with HD may have had difficulties learning or remembering win/loss contingencies of the decks, or they may have failed to consistently take these into account in their card selections. These findings are consistent with current models of frontal-subcortical brain circuits and behavior.     

Brain structure in preclinical Huntington's disease.

BACKGROUND: Huntington's disease (HD) is traditionally conceptualized as a degenerative disease of the striatum. Recent scientific advances, however, have suggested neurodevelopmental contributions and extrastriatal brain abnormalities. This study was designed to assess the morphology of the brain in participants who had previously undergone elective DNA analyses for the HD mutation who did not currently have a clinical diagnosis of HD (preclinical HD subjects). METHODS: Twenty-four preclinical participants with the gene expansion for HD underwent brain magnetic resonance imaging and were compared with a group of 24 healthy control subjects, matched by gender and age. RESULTS: Huntington's disease preclinical participants had substantial morphologic differences from controls throughout the cerebrum. Volume of the cerebral cortex was significantly increased in preclinical HD, whereas the basal ganglia and cerebral white matter volume were substantially decreased. CONCLUSIONS: In individuals with the HD gene mutation who are considered healthy (preclinical for manifest disease), the morphology of the brain is substantially altered compared with matched control subjects. Although decreased volumes of the striatum and cerebral white matter could represent early degenerative changes, the novel finding of enlarged cortex suggests that developmental pathology occurs in HD.     

Locus coeruleus involvement in Huntington's disease.

Numbers and areas of neuronal profiles from sections of brain stem at specific anatomic levels of the locus coeruleus and the dorsal raphe nucleus were measured in 33 patients with Huntington's disease and in 23 age-matched control subjects. Results from the Huntington's disease cases were correlated with severity of neostriatal atrophy and with systematically collected quantitative clinical data. Among the patients with Huntington's disease, lower locus coeruleus neuronal counts, reduced neuronal areas, and reduced locus coeruleus length (distance between rostral and caudal levels) were associated with features of advanced disease, including severity of neostriatal atrophy, severity of dementia, duration of illness, and severity of motor impairment and activities of daily living impairment. By contrast, there was no evidence of neuronal pathology within the dorsal raphe nucleus in Huntington's disease. Pathologic changes in the locus coeruleus may relate to some of the clinical manifestations of Huntington's disease.     

The ubiquitin-proteasome system in Huntington's disease.

The main histopathological feature of Huntington's disease (HD) is the presence of protein aggregates that are gathered into inclusion bodies. So far the mechanisms that lead to inclusion formation as well as their role in the pathogenesis of HD are not totally understood. However, it is well established that inclusion bodies contain components of the ubiquitin-proteasome system. Accordingly, it has been postulated that impairment of this machinery can be one of the causes of this disorder. In this review, the authors summarize the state of current knowledge about this hypothesis.     

The limbic-hypothalamic-pituitary-adrenal axis in Huntington's disease.

The functional integrity of the limbic-hypothalamic-pituitary-adrenal (LHPA) axis was studied in 10 patients with Huntington's disease (HD) and 10 age- and weight-matched control subjects by measuring basal ACTH and cortisol secretion, analyzing the subjects' ACTH and cortisol responses to corticotropin-releasing hormone (CRH) challenge, and by means of the dexamethasone-suppression test (DST). Basal cortisol and ACTH levels were significantly higher in patients with HD compared with controls. Following CRH administration, ACTH responses tended to be blunted in concert with normal cortisol levels. Two patients with HD and one control subject were DST nonsuppressors. Post-DST plasma dexamethasone levels were 57% lower among patients compared with the control group. Only in the HD group age was there an important variable in influencing spontaneous cortisol secretion as well as plasma dexamethasone levels during DST. These results suggest that patients with HD have an endogenous CRH overdrive, possibly due to a loss of (GABA) gamma-aminobutyric acid-containing neurons, and that age might have an effect on the outcome of LHPA axis function tests in patients only.