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Objective: Subtle signs and symptoms of Huntington disease (HD) are often present before impairments reach a point where the neurologic disease is manifest and a diagnosis must be considered. The objective is to examine the prognostic significance of these early clinical signs and symptoms regarding time until unequivocal clinical HD diagnosis. Methods: We analyzed longitudinal data from 218 at-risk but healthy participants in the Huntington Study Group database who had either normal motor examination results or minimal soft motor signs at first observation. This group was followed periodically in HD clinics for up to 4.5 years. We used survival analysis to examine predictors of time until HD diagnosis. Results: Diagnostic prediction was significantly improved using specific, nonredundant items from the Unified Huntington9s Disease Rating Scale. When a movement disorder specialist initially had a global impression of “soft signs” present, cumulative relative risk of diagnosis was 4.68 times greater at 1.5 years of follow-up and 3.58 at 3 years. A neuropsychological test pattern with psychomotor speed 1 SD worse than a semantic knowledge measure increased cumulative risk by 1.99 times at 1.5 years and 1.81 at 3 years. Finally, reports of various subjective HD symptoms increased 3-year relative risk by 2.6 to 3.4. Conclusions: Findings demonstrate that neuropsychological performance and both the clinician rating and the patient subjective perception of motor difficulties contribute nonredundantly to a prediction of Huntington disease diagnosis. These findings may have implications for prognostic assessment of persons at risk and eventually assist with early interventions.

• The rate of disease progression was assessed for 42 persons affected by Huntington's disease who had been neurologically examined at least six times and followed up for at least 3 years. Disease progression was assessed by a disability rating scale administered at each examination. Slow progression was associated with older age at onset of disease and with heavier weight (body mass index) at the first examination. Men tended to have a slower disease progression than did women, and this was particularly evident among men inheriting Huntington's disease from affected mothers. Neither the butyrophenone haloperidol nor the tricyclic antidepressant imipramine were related to rate of progression. Assessments of depression, hostility, and tobacco use were also unrelated to rate of progression. Clinical trials in Huntington's disease should consider these factors when designing therapeutic studies.

With prospects improving for experimental therapeutics aimed at postponing the onset of illness in preclinical carriers of the Huntington's disease (HD) gene, we assessed agreement among experienced clinicians with respect to the motor manifestations of HD, a relevant outcome measure for preventive trials in this population. Seventy-five clinicians experienced in the evaluation of patients with early HD and six non-clinicians were shown a videotape compiled from the film archives of the United States–Venezuela Collaborative HD Research Project. Observers were asked to rate a 2–3-minute segment of the motor examination for each of 17 at-risk subjects. The rating scale ranged from 0 (normal) to 4 (unequivocal extrapyramidal movement disorder characteristic of HD). As measured by a weighted κ statistic, there was substantial agreement among the 75 clinicians in the judgment of unequivocal motor abnormalities comparing scale ratings of 4 with ratings that were not 4 (weighted κ = 0.67; standard error (SE) = 0.09). Agreement among the non-clinicians was only fair (weighted κ = 0.28; SE = 0.10). Even under the artificial conditions of a videotape study, experienced clinicians show substantial agreement about the signs that constitute the motor manifestations of illness in subjects at risk for HD. We expect these findings to translate to a similar level of interobserver agreement in the clinical trial setting involving experienced investigators examining live patients. © 2005 Movement Disorder Society

To determine whether motor, behavioral, or psychiatric symptoms in Huntington disease (HD) predict skilled nursing facility (SNF) placement.Subjects were participants in the Huntington Study Group's Unified Huntington Disease Rating Scale Database (Rochester, NY) between January 1994 and September 1999. Specific motor, psychiatric, and behavioral variables in subjects residing at home and in SNF were analyzed using chi2 and Student's t-tests. For a subset of subjects for whom longitudinal data existed, a Cox proportional hazards model controlling for age, sex, and disease duration was used.Among 4,809 subjects enrolled, 3,070 had clinically definite HD. Of these, 228 (7.4%) resided in SNF. The SNF residents' average age was 52 years, average disease duration was 8.6 years, and they were predominantly women (63%). The SNF residents had worse motor function (chorea, bradykinesia, gait abnormality, and imbalance, p0.0001); were more likely to have obsessions, compulsions, delusions, and auditory hallucinations; and had more aggressive, disruptive (p0.0001), and irritable behaviors (p = 0.0012). For 1,559 subjects, longitudinal data existed (average length of follow-up, 1.9 years), and 87 (5%) moved from home to SNF. In the Cox model, bradykinesia (HR 1.965, 95% CI 1.083 to 3.564), impaired gait (HR 3.004, 95% CI 1.353 to 6.668), and impaired tandem walking (HR 2.546, 95% CI 1.460 to 4.439) were predictive of SNF placement.Institutionalized patients with HD are more motorically, psychiatrically, and behaviorally impaired than their counterparts living at home. However, motor variables alone predicted institutionalization. Treatment strategies that delay the progression of motor dysfunction in HD may postpone the need for institutionalization.

We herein present several cases of female sexual dysfunction related in part to organic neurologic pathophysiology. These cases emphasize the role of the central and peripheral nervous systems in female sexual function.

BACKGROUND During the past decade there has been increasing use of omental transposition to the brain of patients who experienced neurologic sequelae after a cerebral infarction. This paper reports the long-term neurologic effects seen in a patient who underwent omental transposition 31 months after a stroke. Her postoperative follow-up period has been 13 years. CASE DESCRIPTION The patient had an expressive aphasia, a right hemiparesis and the inability to read which occurred immediately after her stroke. After surgery she demonstrated subjective and objective improvement in her speech and mobility. She also regained her ability to read shortly after surgery. CONCLUSION The patient demonstrated that omental transposition to the brain can improve neurologic function in the presence of a long-standing cerebral infarction and that the clinical improvement can be maintained over an extended period.

We compared perfusion of prefrontal, motor, and sensory cortices and basal ganglia in 29 Huntington's disease (HD) patients and nine controls. We found a significant reduction in perfusion in patients with HD of short (6 years, n = 10), medium (6-10 years, n = 8), and long duration (10 years, n = 11) compared with controls. Among short-duration patients, we observed decreases in cortical perfusion before evidence of atrophy on magnetic resonance imaging, suggesting that decreases in neuronal activity, as reflected by perfusion levels, precede gross structural changes. As expected, decreased perfusion was marked in basal ganglia. The extent of cortical perfusion correlated with clinical assessments of functional capabilities as well as with the duration of disease. Prefrontal perfusion correlated with cognitive measures, and motor cortical perfusion correlated with physical disability and activities of daily living scores. We found no significant clinical correlations with sensory cortical perfusion. Single-photon-emission computed tomography may be a sensitive method for assessing disease progression in clinical trials and pharmacologic intervention.

Naltrexone, a specific opiate receptor antagonist, is used clinically in the treatment of heroin addiction and more recently, for the treatment of dyskinesia associated with Huntington's disease (HD). Naltrexone may act as a potential hepatotoxin, as reflected in the elevation of transaminase levels. However, one study concluded that, for a brief treatment period of 12 weeks, there is no contraindication to naltrexone treatment based solely on increased hepatic enzyme values. This study monitored liver transaminase levels, in ten HD patients receiving daily doses, between 50 mg/day and 300 mg/day, of naltrexone for periods of 10 to 36 months. Serum glutamic oxalacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) levels were obtained before treatment and at intervals of 1 to 4 months during treatment. Only one of the ten patients treated with naltrexone had increased levels of both SGOT and SGPT, whereas one other patient showed elevated levels of SGPT. These elevations, which initially appeared dose related decreased to normal limits with continued treatment. Because many of the patients were receiving other medications, a combination of drugs with naltrexone may contribute to the increased transaminase levels seen in two of the patients. In summary, chronic administration of naltrexone in doses up to 300 mg/day for periods up to 36 months does not significantly change hepatic function, as measured by SGOT and SGPT levels.

Distribution of conduction velocities (DCV) of sensory fibers in sural nerve was investigated in three patients with n-hexane poisoning. Measurements were made at 1-2 months, 4-9 months, and at 11, 23, and 36 months after ending exposure. A sural nerve biopsy was obtained from one of the patients. The results indicated the characteristic changes of n-hexane toxicity: myelinated nerve fiber degeneration and paranodal swelling, resulting in changes in the fiber diameter distribution. The DCV documented these changes. After removal from toxic exposure, varying degrees of recovery were studied clinically and evaluated with nerve conduction parameters. The DCV reflects the pathological changes in nerve in toxic neuropathy due to n-hexane.

In studying selected neurological patients and their families over a 2 yr period, the authors learned that appropriate and timely communication relating to disease factors can help patients perform better and assists the family to adjust to the course of the illness. Honest communication actually generated constructive behaviors, namely, family understanding of the disease, positive sick role expectations, and family acceptance of the illness. These three behaviors reinforced patient compliance to treatment, family adjustment to the illness, and maintenance of patient productivity within the limitations imposed by the particular stage of the disease. They also helped the patient to develop a way of life within the family environment in which he could utilize residual strengths.

We studied 52 men with electrophysiologic testing of the bulbocavernosus reflex to determine reflex latency. The bulbocavernosus reflex was demonstrated to be a segmental polysynaptic reflex with cross-over in the sacral spinal cord. Excellent correlation was obtained between prolonged latency and clinical evidence of neuropathy. The examination may be useful clinically to evaluate patients suspected to have sacral cord lesions or pudendal neuropathy (for example impotence, chronic back pain and lesions of the cauda equina and peripheral nerves).

The proportion of deaths attributed to suicide was examined among 506 deceased individuals with diagnosed or suspected Huntington's Disease from New England USA. Comparison of this proportion with that of the general population indicated that the odds of a death being due to suicide in the Huntington's disease group is 8.2 times that of the Massachusetts population for persons aged 50 to 69 yr, but no difference appears in the 10 to 49 yr age group. Among the 157 Huntington's disease patients for whom cause of death was known, the corresponding odds estimates are 23.0 for the 50 to 69 yr age group and 2.7 for the 10 to 49 yr age group. More than half of the suicides occurred in individuals who showed early signs of the illness but who had not been diagnosed, suggesting that suicide may occur more frequently in the early stages of the illness.

Twenty-five patients with late-onset Huntington's disease were studied; motor impairment appeared at age 50 years or later. The average age at onset of chorea was 57.5 years, with an average age at diagnosis of 63.1 years. Approximately 25% of persons affected by Huntington's disease exhibit late onset. A preponderance of maternal transmission was noted in late-onset Huntington's disease. The clinical features resembled those of mid-life onset Huntington's disease but progressed more slowly. Neuropathological evaluation of two cases reveal less severe neuronal atrophy than for mid-life onset disease.

One hundred forty-seven persons exposed to arsenic from well water were evaluated by neurologic examination and nerve conduction studies. Total arsenic concentrations in well water ranged from 1 to 4781 micrograms/L and from 6 to 4964 micrograms/L in urine; a calculated index of arsenic ingestion ranged from 1 to 4521 micrograms/day. No dose-response relationship existed between arsenic ingestion and symptoms or physical findings compatible with peripheral neuropathy. Five of six persons with symptoms or physical findings suggestive of sensory neuropathy had normal nerve conduction velocities. Thirteen persons with elevated arsenic ingestion but no signs or symptoms of neuropathy had one or more abnormal nerve conduction velocities. No dose-response relationship, however, existed between arsenic ingestion and nerve conduction velocities. The authors concluded that arsenic ingestion from well water at the concentrations found in this Alaskan community did not result in clinical or subclinical neuropathy.

This study was designed to determine if Parkinsonian patients exhibited a deficit in motor planning. Thirty adult males, 15 with Parkinson's disease and 15 normal controls, were given a gestural test which had two components. The first component required the symbolic representation of implement usage on verbal command and on imitation (representational items) and the second component required the imitation of non-symbolic hand positions (non-representational items). The results indicated that Parkinsonian patients performed at a significantly lower gestural level on the representational tasks and made significantly more spatial errors on non-representational tasks than the normal controls.

A general computational procedure for the estimation of the distribution of conduction velocities in peripheral nerves is proposed. This distribution is estimated from the compound electrical nerve response and the single fiber response measured either under excised nerve conditions, in locus with needle electrodes or non-invasively with surface electrodes. Several statistical estimation procedures are suggested depending on the amount of knowledge about these nerve signals. The procedure is substantiated by several examples and by the estimation of 48 distributions from data collected in a human population composed of neurologically normal individuals and subjects with diabetic peripheral neuropathy.

Six patients with Huntington's chorea (5 females, 1 male) underwent neuro-urological evaluation because of urological complaints, usually incontinence. Four patients had detrusor hyperreflexia with a normal sphincter and two patients had a normal study, suggesting that their incontinence might be non-organic. A characteristic urodynamic pattern, not previously described, was observed, consisting of choreiform contractions of the abdominal perineal floor muscles during filling with selective suppression of choreiform contractions in the perineum during detrusor contraction.

Patients with alcoholic Korsakoff's syndrome, Huntington's Disease, Alzheimer's Disease or right-hemisphere damage were administered a picture recognition task in which they attempted to associate specific human and animal figures with particular scenic backgrounds. Under one condition (no-story), no explicit verbal cues were provided to help the patients associate the figures with the scenes; in a second condition, stories linking the figures to the background scenes were read to the patients during the study period. Although all four patient groups were impaired in picture-context recognition under the no-story condition, the groups differed significantly in their ability to use the stories to improve their pictorial memory. The Huntington and right-hemisphere patient's picture recognition showed significant improvement when stories were provided, whereas the Korsakoff and Alzheimer patients failed to use this verbal material in a productive manner. The groups also differed in their tendency to make intrusion (i.e., perservative) errors on the picture-context recognition task. These group differences may be related to the combination of language, cognitive and motivational deficits associated with each disease.

• Patients with "recently" diagnosed Huntington's Disease (RHD) were compared on a neuropsychological test battery to patients who have had the disease three to 15 years (AHD) and to intact controls. While the patients with HD showed general nonfocal deficits on the Wechsler Adult Intelligence Scale, the Wechsler Memory Scale, and tests of short-term memory and verbal fluency, the patients with RHD had focal deficits that stressed their memory deficits. The patients with RHD had IQs within the normal range, but their memory quotients, their performance on short-term memory tests, and their ability to search and retrieve from long-term memory were severely impaired. These results suggest that the cognitive deficits of patients with HD do not develop uniformally; memory disorders are early focal signs that precede the patients' more widespread intellectual deterioration.

Arterial blood gases were measured during 7 hours of sleep in 15 patients with severe stable chronic obstructive pulmonary discrease (COPD); 6 awake patients with COPD studies in recumbency for an average of 5 hours served as controls. Mean maximal decrease in arterial oxygen partial pressure (PaO2) (plus or minus SD) was 13.5 plus or minus 3.9 mm Hg for sleeping patients (p less than 0.005) and 5.5 plus or minus 1.7 mm Hg for controls (p less than 0.1), respectively. Changes in pH during sleep were of the magnitude expected with acute changes in arterial carbon dioxide partial pressure (PaCO2) in patients with chronic hypercapnia. Consistent changes in heart rate, respiratory frequency or cardiac rhythm were not observed during sleep. Nocturnal worsening of hypoxemia could be explained by alveolar hypoventilation in six sleeping patients and in five controls; in nine sleeping patients, further impariment of ventilation-perfusion mismatch also contributed to worsening of hypoxemia. There was no relationship between the decrease in PaO2 during sleep and the degree of airways obstruction or the PaO2 level when awake. Because of low PaO2, when awake, a fall in PaO2 during sleep brings values into the steep part of the oxyhemoglobin dissociation curve where slight changes in PaO2 result in marked changes in oxygen content. All patients with COPD whose waking PaO2 was below 60 mm Hg had PaO2 below 50 mm Hg during sleep; nocturnal oxygen therapy should be considered in such patients, particularly in the presence of polycythemia or troublesome right-sided heart failure.

Conditioning of Hoffman's reflex in 7 normal and 7 parkinsonian subjects before and after L-dopa therapy was tested using standard methods. Features of the raw data, including timing, duration, and magnitude of facilitation, were estimated optimally with nonlinear least-squares for each test sequence on each subject. For each parkinsonian subject there was a consistent trend with treatment for several features to return to the average features of the normal group; to varying degrees, clinical reduction in bradykinesia and rigidity was also observed in all cases. These results are in general agreement with similar previous studies reported by other investigators but offer stronger statistical evidence and differ in certain finer details.

In various neurologic and non-neurologic diseases inappropriate hypertonicity of the external sphincter during micturition may cause outlet obstruction. Heretofore therapy for these disorders has been surgical: pudenal neurectomy or external sphincterotomy. These procedures are not without complication (incontinence, impotence, hemorrhage). A medical approach to this disorder is therefore warranted. In a selected group of patients with external sphincter spasm diagnosed by concomitant sphincter electromyography, cystometrography, and voiding cystourethrography, dantrolene sodium (Dantrium) therapy was instituted. Follow-up studies have shown this drug to be effective in treating this disorder.

Summary We have evaluated at length an individual who had as a major neurological defect an impaired ability to recognize the nature of heard non-verbal sounds, that is, auditory agnosia. Wood et al.: (1971) have demonstrated that ≪different neural events occur in the left hemisphere during analysis of linguistic vs non-linguistic parameters of the same acoustic signal≫. This case provides additional clinical support for the theoretical position that there may be two central auditory processing mechanisms, one treating linguistic inputs and the other non-linguistic inputs.

Sebum production was measured on the foreheads of 21 patients with Parkinson's disease before and during long-term L-dopa treatment. A statistically significant decrease in the amount of sebum was demonstrable during treatment although considerable variation in responsiveness was observed. No correlation between the dose of L-dopa and the degree of sebaceous gland inhibition could be established. The quantitative reduction of sebum could not be related to the degree of neurologic improvement.

The principles of a general method for modeling the dynamics of interacting neural cell populations are presented. Hoffman's reflex, an electrically evoked spinal reflex of the lower leg, is used as an illustration of the method. Since the variables and structure of the resulting model are in direct correspondence with measurable physiological and anatomic quantities, it is suitable for the prediction of nervous system activity over a wide range of time scales and stimulus amplitudes. A relatively efficient representation of feedback interconnections among neural cell populations is also obtained.

Multiple sclerosis is a demyelinating disease of the central nervous system, often producing abnormalities in sexual function and urinary control. Eighty-six patients with this disorder were referred to our neurourologic facilities for evaluation (45 women and 41 men). Symptomatic voiding dysfunction was present in 84 patients (97 per cent). Sexual dysfunction was present in 29 of the 41 men (71 per cent). Neurourologic evaluation was performed by rapid-fill carbon dioxide cystometry and perineal floor needle electromyography. Several neurourologic patterns were identified in multiple sclerosis patients: the most common cystometry pattern was detrusor hyperreflexia (76 per cent) and the most common electromyography finding was vesico-sphincter dyssynergia (50 per cent). Voiding symptoms alone were not found to correlate with neurourologic findings. The presence of bilateral extensor plantar reflexes was found to indicate the possibility of vesico-sphincter dyssynergia. The addition of sacral-evoked responses to the neurourologic evaluation was useful in the identification and localization of occult sacral cord pathology and was of special significance to men with sexual dysfunction undergoing evaluation for neurogenic impotence. The combination of abnormal perineal electromyography, abnormal sacral latency and detrusor hyperreflexia was suggestive of multilevel spinal cord dysfunction and, possibly, has diagnostic as well as therapeutic significance. Neurourologic patterns were found to change in 4 of 9 patients re-evaluated because of symptom changes or poor treatment responses. Neurourologic testing in multiple sclerosis patients may be used to identify pathologic lesions, characterize sexual and voiding dysfunctions, corroborate neurologic diagnosis in doubtful cases and form a basis for rational treatment planning.

Twenty-six patients with Huntington's disease (HD) and three subjects at risk for HD were evaluated by computed tomographic, neurologic and neuropsychological examinations. These data were used to delineate the sequence of structural changes in early and intermediate HD, and the relationship of these changes to impairment of neurologic and cognitive function. CT scans documented an early neostriatal-frontal focus of atrophy in HD which spreads caudally over the cerebral cortex during the course of the disease. Chorea was positively correlated with caudate atrophy. Functional and cognitive (especially memory and visuospatial) impairments were strongly related to the degree of atrophy. Multiple regression analyses of CT and neuropsychological data further demonstrated that neostriatal changes make a significant contribution to the cognitive as well as to the motor impairments of HD patients.

Dopaminergic-cholinergic balance is a clinically observable phenomenon in Parkinson's disease and in L-dopa-induced dyskinesia. In a series of 30 patients with a variety of choreiform movement disorders, including Huntington's disease, L-dopa-induced dyskinesia, and tardive dyskinesia, we have been unable to dernonstrate consistent cholinergic responsiveness. Intravenous physostigmine reduced chorea in Huntington's disease in only two of 12 patients, whereas choreiform movements were abolished or suppressed in five of seven patients with L-dopa-induced dyskinesias.

Studies of the blink reflex were undertaken in twelve normal subjects during wakefulness and different sleep stages. The early R1 and the late R2 components of the reflex were analyzed. R1 was present in only one subject during stage I sleep and subsequently disappeared in stage II to IV. In all subjects, R2 was gradually diminished and totally disappeared during stage IV. During the REM stage, R1 was seen in only four-out-of-twelve subjects but all R2 returned. Alterations of R1 and R2 of the blink reflex during different sleep stages suggest that the underlying mechanism includes both supranuclear and infranuclear activities. Our finding strengthens further the notion of dual hyponogenic mechanisms for sleep.

We conducted a double-blind controlled study of individuals exposed to arsenic trioxide in a copper-smelting factory. Subjects fell into three categories of peripheral neuropathy: none, subclinical, and clinical. The subclinical group had no symptoms or signs of numbness or reduced reflexes, but did have reduced nerve conduction velocity and amplitude measurements. Clinical neuropathy groups had signs and symptoms of neuropathy and electrophysiologic abnormalities. The clinical and subclinical groups correlated with increased content of arsenic in urine, hair, and nails. The incidence of subclinical and clinical neuropathy was greater in arsenic workers than in unexposed controls.

Patients with Huntington's disease (HD), patients with alcoholic Korsakoff's syndrome, and normal control subjects were compared on tests of skill learning (mirror reading) and verbal recognition. Like previously reported results, the patients with Korsakoff's syndrome acquired the mirror-reading skill at a normal rate but were severely impaired in their recognition of the words used on the mirror-reading task. In contrast to the amnesic patients, the demented patients with HD were retarded in their ability to acquire this skill but showed normal verbal recognition. Besides emphasizing substantial differences in the anterograde substantial differences in the anterograde memory disorders of these two patient populations, the results suggest that the memory disorder of patients with HD may appear much more severe when recall rather than recognition test paradigms are employed. This failure of recall by the patients with HD may be due to an inability to generate strategies necessary to search their short- and long-term memories.

Retrograde amnesia was assessed in demented and non-demented Parkinson’s patients using a test of remote memory spanning the years from 1920-1979. Results indicated that the demented patients 1) scored significantly below normal controls and 2) had equal impairment for all time periods. This pattern was like that seen in other dementing illnesses (i.e., Huntington’s and Alzheimer’s diseases), but different from that in amnesic disorders, such as Korsakoff s syndrome. The data, therefore, suggest qualitative differences in pattern of remote memory loss between the dementias and amnesic syndromes.

Lower urinary tract function was studied in patients with Parkinson’s disease. A significant proportion of patients receiving levodopa manifested clinical and radiological evidence of bladder outlet obstruction. We believe that neuropharmacologic bladder neck obstruction may be caused by the alpha-adrenergic properties of the metabolites of levodopa.

A computer program which optimally estimates the main features of the H-reflex conditioning curve from experimental data has been developed. The features (Fig. 1) include: absolute refractory period, latency, and duration of facilitation, recovery time, and the ratio of response amplitudes during refractoriness and at peak facilitation. These numbers provide a sound basis for interpatient statistical comparison of H-reflex curves, particularly in the establishment of “normal” and “abnormal” findings for H-reflex conditioning studies.

Summary Patients with Huntington's Chorea and alcoholic Korsakof's disease were compared on six tests of short-term memory (STM) and of encoding capacity. While the alcoholic Korsakoff patients demonstrated STM disorders related to an increased sensitivity to proactive interference (PI) and to failures in semantic encoding, the Chorea patients had a different pattern of deficits. The Chorea patients, like the Korsakoffs, had STM deficits, but their memory performance did not improve with reductions in PI, and they had different types of encoding deficits than did the Korsakoff patients. These results demonstrate that information processing tasks can be used to empirically differentiate amnesic patients with normal I.Q.'s from patients 'with dementia-related memory impairments.

Psychiatric complications of L-dopa treatment of Parkinson's disease at our hospital were less frequent and severe than reported at other institutions. Psychosocial factors were much more prominent in the complications that did occur than a pharmacologic effect of L-dopa. Interest in the connections between L-dopa, catecholamine metabolism and emotional disorder should not lead to neglect of medical-psychological aspects of L-dopa therapy.

Variability of expression of the Huntington's disease (HD) gene is illustrated in 2 families with linkage of DNA restriction fragment length polymorphism to the short arm of chromosome 4. In 1 family, affected persons from 3 generations show 50-year variation of onset age. The member with the latest onset age (67) died at 91 with autopsy-confirmed HD. The next generation had hypotonic chorea beginning in the 4th decade with death in the 5th. In the 3rd generation, a rigid patient, inheriting the illness from an affected father, had a much earlier onset at 16, while her siblings had chorea beginning in the 3rd decade. In the 2nd family, several members had cerebellar signs, chorea, and dementia. MRI and CT revealed olivoponto-cerebellar and striatal atrophy. These phenotypes may be the result of different allelic genes at the HD locus or unlinked autosomal modifying loci influencing the expression of the HD gene.