Cognitive manifestations of Huntington disease in relation to genetic structure and clinical onset.

OBJECTIVE: To examine the cognitive manifestations of Huntington disease (HD) with respect to age, clinical onset, progression, and genetic analyses. DESIGN: Case series of people with HD or at risk (AR) for HD. SETTING: Movement disorders and medical genetics clinics. PARTICIPANTS: Volunteer sample of 50 patients with HD and 127 AR adults. MEASURES: Neuropsychological evaluation was conducted with multiple measures of cognitive function (intelligence, memory, attention, executive, spatial, language), strength, manual speed/dexterity, somatosensory function, and mood. Quantitative molecular genetic analysis by means of polymerase chain reaction was conducted on 31 patients with HD and 86 AR subjects. RESULTS: In clinical HD, cognitive impairment correlated with number of years affected but not age at onset. The linear regression had a negative intercept, suggesting impaired cognitive function by the time of onset. In AR gene carriers, lower cognitive performance correlated with more trinucleotide repeats. In clinical HD, trinucleotide repeats interacted with disease chronicity such that more repeats were associated with worse performance over time; the overall effect of this was small compared with the effect of disease chronicity alone. Except for one AR subject, mood state was not associated with cognitive performance in either patients with HD or AR subjects. CONCLUSIONS: Cognitive decline appears to start before clinical onset of HD and is correlated with the number of trinucleotide repeats. Subsequent cognitive decline is primarily a function of number of years affected, although there is evidence that the presence of more trinucleotide repeats is associated with faster deterioration.

Acute effects on neuropsychological function and quality of life by high-dose multiple daily fractionated radiotherapy for malignant astrocytomas: assessing the tolerability of a new radiotherapy regimen.

Cognitive and other quality of life measures were assessed in 29 patients with supratentorial malignant astrocytomas before and after high-dose (8000 cGy) multiple daily fractionated radiotherapy. Assessments were done immediately before and after radiotherapy. Patients completed a neuropsychological evaluation and the Functional Living Index: Cancer (FLIC). Spouses completed the Family Environment Scale and the Profile of Mood States. Cognitive abilities generally improved over the course of radiotherapy. Occasionally, deterioration of potential clinical importance was observed on functions associated with the tumour site. Quality of life as assessed by the FLIC was stable in most cases and improved in five, but deteriorated in three patients. Families showed slightly less Conflict and slightly more Cohesion than the norm; this was especially so when patients had greater cognitive deficit. Emotional state of spouses was variable, with increased fatigue or reduced activity most commonly reported, followed by depression and anxiety. Mostly this improved with time or remained stable, but two spouses reported worsening emotional state. Results are generally encouraging for tolerance of this radiotherapy protocol, although they demonstrate that limited adverse effects may occur in some cases.

Failure of metacontrol: breakdown in behavioural unity after lesion of the corpus callosum and inferomedial frontal lobes.

A right-handed man suffered aneurysmal haemorrhage with lesions of the genu and body of the corpus callosum and the inferomedial frontal lobes bilaterally (right more than left). He exhibited remarkable breakdown in behavioural unity characterized by conflict between the two sides of the body, actions inconsistent with verbalizations, and internal conflict over control of the left hand. A major feature of the deficit was its temporal variability. This is interpreted as reflecting intermittent failure of metacontrol processes, which are neural mechanisms for maintaining behavioural unity. Medial frontal structures and their interconnections through the corpus callosum appear particularly important in the maintenance of metacontrol.

Psychiatric morbidity in patients with HIV infection.

A psychiatric examination was conducted on 144 patients at various stages of HIV infection and on 29 controls found to be seronegative. One-half of the control group had at least one DSM-III-R Axis I diagnosis, most commonly cannabis abuse, alcohol abuse, or adjustment disorder. Compared to this baseline, HIV-infected subjects had higher rates of adjustment disorder. AIDS patients were also more likely to suffer from organic mental disorder. The rate of unemployment increased as the disease progressed. Major depression was seen in only ten patients, and there were no differences between controls and HIV-infected subjects. Formal assessment of mood state and feelings of pessimism also showed no differences among the groups. The importance of helping improve the patient's lifestyle through the control of alcohol and drug abuse is underscored.

High-altitude mountaineering and brain function: neuropsychological testing of members of a Mount Everest expedition.

Concern has been raised regarding the possibility that hypoxic conditions encountered during high-altitude mountaineering may have lasting harmful effects on the human brain. Members of an expedition to Mount Everest completed a series of neuropsychological tests before and after the expedition. Exposure to altitudes above 7,200 m was limited to a maximum of four consecutive nights, separated by rest periods at lower altitudes. No significant decline in performance was observed on any test. The subjects also completed a short series of tests at different altitudes during the expedition. No significant deterioration was observed at altitudes up to 7,500 m. There do not appear to be lasting harmful effects on brain function under these conditions.

Presymptomatic neuropsychological impairment in Huntington's disease.

Ten asymptomatic individuals at risk for Huntington's disease (HD) were determined by the use of linked DNA probes to have a high (HD+ group) or low (HD- group) probability of having inherited the mutant gene. Neuropsychological examination, performed without knowledge of DNA results, revealed impairments in five of seven subjects in the HD+ group. Abnormalities were related to visuospatial abilities or to functions associated with the frontal lobes. All three subjects in the HD- group showed no neuropsychological impairment. Statistical analyses confirmed differences between the HD+ and HD- groups. Affected parents of subjects were at least 12 years older at symptom onset. These results demonstrate that clear neuropsychological impairment may be present in HD even when overt signs and symptoms are not expected for a number of years.