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.     

Horizontal and vertical saccadic eye movement abnormalities in Huntington's chorea

With a newly developed infrared reflection technique, voluntary saccadic eye movements (VOLS), visually evoked saccades (VES) and unsuppressed visually evoked reflex saccades (USVERS) were measured in 11 patients with Huntington's chorea. Abnormalities, including latency increase, peak velocity decrease and undershoot dysmetria with multiple step saccades were found in all types of saccadic eye movements. Peak velocity decrease and undershoot dysmetria can be explained by dysfunction of the brainstem reticular formation in Huntington's chorea. USVERS and square wave jerks occurred abnormally frequently and showed direction-dependent differences. Both were more frequent in horizontal than in vertical direction. Frequency of USVERS and square-wave jerks tended to be correlated. These findings point to disinhibited superior colliculi as a possible common supranuclear origin of USVERS and square-wave jerks in Huntington's chorea.     

Plasma glutamate decarboxylase activity in neuropsychiatry

Plasma glutamate decarboxylase (GAD) activity was measured in patients with endogenous psychoses and neurologic diseases. Unmedicated schizophrenic patients showed no difference in plasma GAD levels compared to controls. Administration of neuroleptics together with anticholinergic agents increased plasma GAD activity in schizophrenic patients. Compared to controls, patients with major depression and bipolar illness showed significantly lower GAD activity. No effect of antidepressants and minor tranquilizers on plasma GAD activity was found. Relatively lower GAD activity was shown in neurotic patients. The enzyme activity in plasma of patients with Huntington's chorea (HC) was lower than control levels. The plasma GAD concentrations correlated with cerebrospinal fluid concentrations in five HC patients.     

Homovanilic acid in Huntington's disease and Sydenham's chorea.

Homovanilic acid (HVA) was determined in the lumbar CSF of 12 patients with Huntington's disease and 12 with Sydenham's chorea before and after probenecid administration. The means of HVA concentration (basal and after probenecid) were lower in those with Huntington's disease than in controls, and were even lower in a sub-group characterised by increased tone and slowness of voluntary movement. There was no correlation between CSF HVA values and the severity of abnormal movements, nor with length of the illness and age of the patients with Huntington's disease. The mean basal HVA concentration did not differ from controls in those with Sydenham's chorea but the accumulation with probenecid was significantly lower. These results suggest a decrease in cerebral dopamine release in both forms of chorea.     

Somatosensory evoked potentials in Huntington's chorea

Somatosensory evoked potentials were measured in 21 patients with Huntington's chorea and 12 controls. Central brain conduction time was normal. Early cortical component amplitudes were reduced in the patient group, latencies were normal. These abnormalities probably can be attributed to cortical dysfunction in Huntington's chorea. No indication of brain-stem dysfunction was found.     

The EEG in Huntington''s chorea: a clinical and neuropathological study

The EEGs are reported on a group of 95 patients with Huntington's chorea. Thirty one showed little activity of any kind, and in particular no alpha rhythm above 10 μV in amplitude was seen. Only those records which still met these criteria when re-examined were included in the `low voltage' category. EEGs in this category occurred significantly more frequently in institutionalized patients and in those with a positive family history of Huntington's chorea, dementia, and choreiform movements together. Computer averaged responses to light and sound were found in the three patients examined, though their routine EEGs were low voltage. Neuropathological examination confirmed a clinical diagnosis of Huntington's chorea in 14 patients investigated. There was a statistically significant association between cortical atrophy, including the frontal lobe, and a `low voltage' EEG. It was concluded that the low voltage record, though not specific for Huntington's chorea, was rare in other neurological disorders. The EEG is therefore of value in patients suspected of having Huntington's chorea as well as in various presenile dementias.     

Cerebrospinal fluid choline in extrapyramidal disorders

Cerebrospinal fluid from patients with Parkinson's disease and Huntington's chorea has been investigated with regard to the concentration of choline. In Parkinson's disease the choline concentration of lumbar spinal fluid was not different from that of a control group, nor was it related to medication, duration of illness, or severity of symptoms. A comparison between choline in ventricular cerebrospinal fluid from patients with Parkinson's disease and with intention tremor showed no significant differences. Patients with Huntington's chorea had a lower concentration of choline in lumbar spinal fluid as compared with a control group. The results are discussed in relation to the possible sources of cerebrospinal fluid choline.     

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.     

A morphometric reevaluation of Huntington's chorea with special reference to the large neurons in the neostriatum

In order to reevaluate the quantitative changes in the neostriatum of Huntington's chorea (HC), sections of the caudate head and putamen from 4 HC and 5 control cases were treated with Klüver-Barrera stain and the nuclear area of the neurons was measured by a digitizer. The number of neurons of different sizes was evaluated statistically. This study revealed a significant decrease in the number of large neurons (nuclear area; greater than 121 microns 2) as well as a severe decrease in the number of small neurons (nuclear area; less than 80 microns 2) in the neostriatum of HC. There was a parallel degree of neuronal loss in the upper and lower portions of both caudate head and putamen. The degree of neuronal loss was slightly more severe in the putamen than in the caudate head. The depletion of the large neurons was not correlated with the loss of small neurons. The number of medium-sized neurons (nuclear area; 81-120 microns 2) showed no statistically significant change.     

HLA antigen frequencies in patients with huntington's chorea and their relatives

Summary Twenty patients with Huntington's chorea and 30 family members were typed for 30 antigens of the HLA-A, B, and C series. There was an increased frequency of HLA-BW 16, significant at the 1%-level. After correcting for multiple inferences, the association of HLA-BW 16 with Huntington's chorea was no longer statistically significant. There was also no reliable indication of coupling between HLA antigens and Huntington's chorea in the family studies.

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Zusammenfassung Bei 20 Patienten mit Chorea Huntington und 30 Angehörigen wurden 30 HLA-Antigene der A-, B- und C-Serie bestimmt. Es fand sich eine Frequenzvermehrung von HLA-BW 16, die auf dem 1%-Niveau signifikant war. Nach einer Korrektur für statistische Fehler ersten Grades bestand keine Signifikanz mehr. Auch bei den Familienuntersuchungen fand sich kein sicherer Hinweis für eine Kopplung der HLA-Antigene mit dem Choreagen.

     

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.     

Pallidal GABA and chorea in Huntington's disease

Summary Neurochemical correlates of chorea in Huntington's disease were studied using striatal and pallidal tissue taken post mortem from patients with mild and severe chorea. While GABA was decreased in all these areas in Huntington's disease, patients with mild chorea had significantly less GABA in the medial pallidum than did those with severe chorea. There was no relationship between the degree of chorea and concentrations of dopamine or its metabolite. Thus the chorea of Huntington's disease may relate to the balance of residual GABAergic innervation between specific areas of the basal ganglia, consistent with primate models of dyskinesias.     

BLINK REFLEX IN HUNTINGTON''S CHOREA AND PARKINSON''S DISEASE

The electrically-evoked late response (R2) of the blink reflex has been determined in 8 well-documented cases of Huntington's chorea and in 19 Parkinsonian patients. The results obtained from the two groups are compared with those from 10 normal subjects. A statistically significant difference of some components of the blink reflex was obtained when the three groups were compared. In both pathological conditions, the habituation index, latency and differential latency can be considered to represent the opposite extremes from the same scale, providing further evidence of the neurophysiological antagonism between the two disease states. The blink reflex pattern in Huntington's chorea probably reflects a diminished brain-stem interneurone basal activity through an over-inhibition of dopaminergic receptors in the striatum. The electrophysiological analysis of the blink reflex in incipient Huntington's chorea can provide an objective diagnostic assessment. It might be an effective method of detection for dopaminergic-activated carriers asking for genetic counseling.     

Parasympathetic function in Huntington's disease

Parasympathetic function in 7 Huntington's chorea patients with a duration of the disease ranging from 1 to 20 years, was evaluated by studying R-R intervals during quiet and deep breathing and Valsalva manoeuvre. All 7 patients were free of neuropathy, orthostatic hypotension, heart or lung disease and had had no medication for at least 15 days prior to hospitalization. Seven normal subjects served as controls. On the whole, the responses of the Huntington's chorea patients were not significantly different from those of the controls. Abnormal responses to all the tests were received in only one patient and a low R-R variability during deep breathing in the youngest patients. Unlike other Central Nervous System degenerative disorders, in Huntington's disease parasympathetic autonomy seems to be sufficiently preserved.     

A blinded study of the suppressibility of involuntary movements in Huntington's chorea, tardive dyskinesia, and L-dopa-induced chorea

Videotapes of patients with Huntington's chorea, tardive dyskinesia (TD), and L-DOPA-induced chorea in Parkinson's disease were taken while the patients were seated with their legs dangling. The videotapes were scored in a blinded fashion for suppressibility of dyskinesias. Most patients with TD or L-DOPA-induced chorea substantially suppressed their involuntary movements, whereas most patients with Huntington's chorea did not. There was a small overlap between the TD and Huntington's chorea groups and suppressibility therefore could not absolutely distinguish between them. Suppressibility testing may nonetheless be a valuable clinical tool since a good, excellent, or complete suppressibility rating was highly suggestive of TD but not Huntington's chorea. TD and L-DOPA-induced chorea may be more pathophysiologically similar to each other than either is to Huntington's chorea.     

Late onset levodopa responsive Huntington's disease with minimal chorea masquerading as Parkinson plus syndrome

Huntington's disease is characterised by hyperkinetic movements, mainly chorea, cognitive dysfunction, and psychiatric abnormalities. Non-dopa responsive parkinsonism occurs in the later stages of choreic disease or as the predominant feature of juvenile patients (Westphal variant). Late onset Huntington's disease presenting as levodopa responsive parkinsonism is rare. A series of four patients with late onset Huntington's disease presenting as levodopa responsive parkinsonism and cardiovascular dysautonomia, initially misdiagnosed as multiple system atrophy (MSA) in three patients, is reported. Levodopa treatment did not unmask significant chorea. These cases suggest the presence of a distinct phenotypic variant of Huntington's disease to be added to the differential diagnosis of other akinetic rigid syndromes.     

Huntington's chorea associated with normal pressure hydrocephalus.

Two patients with Huntington's chorea (HC) developed a gait disturbance more suggestive of normal pressure hydrocephalus (NPH) than HC. The diagnosis of NPH was confirmed by pneumoencephalography and isotope cisternography. Both patients were shunted and both showed an improvement not only in their gait but, unexpectedly, a decrease in their abnormal involuntary movements (AIMs). The association of HC with NPH is discussed.     

Neuroendocrinologic findings in patients with untreated Huntington's chorea

Huntington's chorea (HC) was studied in 14 untreated patients, in six patients receiving long-term neuroleptic treatment, and in four patients after drug withdrawal. Our results showed that patients with HC may be divided into three groups, otherwise clinically indistinguishable, on the basis of growth hormone responsiveness to dopaminergic stimuli. The existence of subpopulations of patients with HC must be considered in further studies on these subjects.     

Regional distribution of choline acetyltransferase in the human brain: changes in Huntington''s chorea.

A stereotaxic method of tissue sampling has been developed permitting detailed studies of the distribution of choline acetyltransferase (CAT) in brains from controls and from patients suffering from Huntington's chorea. The characteristic pattern of CAT distribution within extra-pyramidal structures is described. In Huntington's chorea, CAT is unevenly reduced in several brain regions particularly in the rostromedial part of the caudate nucleus. The results indicate a preferential degeneration of neostriatal cholinergic neurones in Huntington's chorea.     

Regional Specificity of Brain Atrophy in Huntington''s Disease

The present study analyzes the relationship between cortical and subcortical brain volumes in patients with Huntington's disease. The brains of seven patients with a clinical diagnosis and positive family history of Huntington's disease and 12 controls were collected at autopsy with consent from relatives. Detailed clinical assessments were available for all study subjects with genotype confirmation for patients with Huntington's disease. Volume analysis of the brain on serial 3-mm coronal slices was performed as previously described. All patients with Huntington's disease exhibited significant brain atrophy resulting from volume reductions in both cortical and subcortical grey matter. Atrophy of the cortex was relatively uniform, although the medial temporal lobe structures were spared. The caudate nucleus and putamen were strikingly reduced in all cases and this atrophy correlated with the severity of cortical atrophy, suggesting an associated disease process. The rate of cortical but not subcortical atrophy correlated with CAG repeat numbers. Loss of frontal white matter correlated with both cortical and striatal atrophy. Age of onset of chorea correlated with the amount of subcortical atrophy, while duration of chorea correlated negatively with atrophy of the white matter. These results suggest a more widespread and global disease process in patients with Huntington's disease.