Oculomotor disorders in Huntington''s chorea.

Electro-oculographic recordings were obtained from 11 patients with Huntington's disease. Significant reduction of saccadic velocity was constantly found. In all the patients vertical saccades were much more impaired than horizontal. When present, vertical saccades showed long latency, low amplitude, low velocity, and disturbances related to blinking. Following movements were jerky, and ability to perform repeated rhythmic movements was impaired. These results are in agreement with previous observations and underline the selective defect of rapid movements as a characteristic feature of Huntington's disease. Further, they suggest a possible correlation between the difficulty in performing repeated ocular movements and the impaired execution of gestural sequences involving a succession of different fundamental movements.     

Hepatic morphology in Huntington''s chorea.

Liver biopsy specimens from six patients with Huntington's chorea were examined locally and referred with clinical information to three colleagues abroad experienced in the interpretation of liver biopsy specimens. The minor and inconsistent abnormalities reported upon were of non-specific character. The suggested interrelation between damage to cerebral neurones and hepatocytes in Huntington's chorea was not substantiated by this study.     

Levodopa and Huntington''s chorea

Two patients with Huntington's chorea are reported whose psychiatric and neurological symptoms greatly improved after treatment with L-dopa. In both cases the basal values of CSF HVA were markedly decreased, being increased by the treatment with L-dopa.     

Altered growth hormone release in Huntington''s chorea.

Glucose tolerance tests have been performed on five patients with Huntington's chorea and no difference in response has been observed compared with seven controls. Insulin tolerance tests have been performed on 12 patients with Huntington's chorea and 10 controls. Blood samples were taken at regular intervals for 75 minutes and analysed for blood glucose, insulin, and growth hormone (HGH). There was no difference between the groups in the hypoglycaemia which developed. The patients, however, had an earlier elevation of HGH than the controls. The difference was highly significant (P less than 0.001, P less than 0.02) 30 and 35 minutes after the intravenous injection of insulin. The patients, although awake, ceased to have choreiform movements for at least the last 60 minutes of the insulin tolerance tests. Our observations of HGH release imply that hypothalamic activity is altered in Huntington's chorea. Further observations of HGH release may therefore be of value in its diagnosis.     

Platelet monoamine oxidase activity in Huntington''s chorea.

The possibility that genetically determined abnormalities in the monoamine oxidase of certain central nervous system aminergic neurones may play a part in the pathology of Huntington's chorea was investigated using human platelet monoamine oxidase. Significantly elevated monoamine oxidase activity was found in male patients compared to control subjects suggesting this may be a screening test for this disorder. Low monoamine oxidase activity was associated with a better clinical response to drugs.     

Evidence of genetic heterogeneity in Huntington''s chorea

In an extensive study of Huntington's chorea in Queensland evidence was found to support an old observation that the magnitude of the variation in the symptom complex of the disease between different families is sufficient to suggest that there may be more than one form of Huntington's chorea allele present in the community. Analysis of data concerning age at onset indicates that at least two separate forms of the disorder may exist.     

Tiapride in the treatment of Huntington''s chorea

Twenty-two patients with Huntington's chorea were investigated in a double-blind controlled cross-over trial. The effect was measured by counting the number of involuntary movements from video-recordings and by a Doppler-radar device. Besides these methods, subjective assessments were made on analogue scales by patients, family, nurses and attendant doctors. The quantitative methods revealed no significant diminution of the involuntary movements in the Tiapride therapy period. The subjective evaluation turned out to be useless because of many inconsistent answers.     

2-Dimethylaminoethanol (Deanol) in Huntington''s chorea

A double-blind crossover trial with 2-dimethylaminoethanol (Deanol), a possible precursor of brain acetylcholine, was carried out in nine patients with Huntington's chorea. It was found to be ineffective in inducing any alteration in hyperkinesia.     

Brainstem reflexes and brainstem auditory evoked responses in Huntington''s chorea.

Blink reflex, corneal reflex, jaw reflex, exteroceptive suppression in masseter muscles and brainstem auditory evoked potentials were measured in 20 patients with Huntington's chorea and 12 controls. A significantly increased latency of the second component of the homolateral and heterolateral blink reflex was found in the patient group as compared with the controls. The other investigations revealed no significant differences between patients and controls except for some facilitation of the jaw reflex in the patient group. Increase of second component latency of the blink reflex in the presence of normal corneal reflexes is suggestive of functional impulse conduction disturbance in the lower brainstem. It is discussed whether in Huntington's chorea this is to be attributed to alterations of cortical or striatal influence or to local brainstem abnormalities.     

Amine metabolites in the cerbrospinal fluid in Huntington''s chorea

The amine metabolites HVA and 5-HIAA in the lumbar CSF of 15 patients with Huntington's chorea were determined. A negative correlation was found between the severity of symptoms and the CSF HVA, but not 5-HIAA levels. The mean HVA concentration was lower than that of a group of patients with miscellaneous neurological disorders, similar to that of a group with miscellaneous psychiatric disorders and higher than that of a group with Parkinson's disease. The mean 5-HIAA concentration was similar to that of the neurological group and higher than those of the groups with psychiatric disorders or Parkinson's disease. CSF HVA and 5-HIAA concentrations of a single patient with severe akinetic rigid Huntington's chorea were similar to those found in Parkinson's disease. The findings are discussed in relation to previous neuropathological observations and to reported effects of drugs on the choreic symptoms.     

Growth hormone and prolactin response to bromocriptine in patients with Huntington''s chorea.

The growth hormone (hGH) and prolactin (hPRL) responses to oral bromocriptine were studied in two groups of patients with Huntington's chorea and in seven healthy control subjects. The patients included six patients who had previously been treated with phenothiazines and six patients who had not received phenothiazine treatment. All medication was stopped 72 hours before the investigation which involved taking blood samples for up to 210 minutes after taking bromocriptine (2.5 mg). Plasma samples were analysed for hGH and hPRL. There was no significant difference in basal hGH concentrations between the patients and control subjects. The hGH response to bromocriptine varied in the individual patients but the concentrations were significantly lower in the patients compared with the controls between 160 and 210 minutes. The basal concentrations of hPRL were also not different, apart from the findings of elevated hPRL concentrations in three patients previously treated with phenothiazines. The patients and control subjects showed a consistent fall in hPRL concentrations after taking bromocriptine. The lower peak hGH response to bromocriptine found in the patients suggests that there may be an alteration of dopaminergic neurones mediating hGH release.     

Free and conjugated CSF and plasma GABA in Huntington''s chorea

Free and conjugated GABA concentrations were measured in CSF and plasma from 28 patients with manifest Huntington's chorea (HC) and 30 age- and sex-matched controls. GABA was determined by ion-exchange chromatography with fluorimetric detection (IE/F). Free and conjugated CSF GABA was significantly decreased in prolonged HC with advanced disease states and was suggested practicable as an additional diagnostic tool. However, in younger patients (less than 40 yrs) with a short period of HC (less than 2 yrs) an overlap with the age-matched normal range indicated GABA measurement inadequate to early diagnosis nor predictive for offspring at risk. An age-dependent decrease of conjugated CSF GABA was observed in patients and controls. The more pronounced decrease in patients might reflect the neurodegenerative feature of HC.     

Huntington''s chorea: a prevalence study in the Florence area

A prevalence study of Huntington's chorea in Florence area in the period 1970-1979. Two clusters have been identified and the frequency of subjects heterozygote for Huntington's gene has been determined for planning Public Health intervention and the preparation of correct genetic counselling.     

Electron spin resonance studies of erythrocyte ghost cells in Huntington''s chorea

There is accumulated evidence which suggests that the primary gene defect in the autosomal dominant disease of Huntington's Chorea, is given expression as a generalised membrane abnormality in peripheral tissues. Several publications claim to be able to detect a difference between HC patients and controls by means of the electron spin resonance (ESR) technique. We have examined the electron spin resonance spectra of the spin probe 4-maleimido-2,2,6,6-tetramethylpiperidinooxyl (MAL-6) when incorporated into the membranes of erythrocyte ghost cells of 22 patients with HC and 47 controls, in 2 series of controlled, blind studies and we were unable to detect any difference between HC patients and normals. We conclude that the ESR technique with the probe used is not a sufficiently reliable test for accurate differentiation of HC patients from controls and is certainly not suitable as a method for the diagnosis of potential carriers of this disease.