E. A. van der Velde

Sleep, excessive daytime sleepiness and fatigue in Parkinson's disease

SummaryThe objective of this questionnaire-based survey was to evaluate the prevalence and causes of sleep disturbances in 90 nondepressive patients with Parkinsons disease (PD) and 71 age-matched healthy subjects. We also assessed the prevalence and characteristics of excessive daytime sleepiness (both groups) and excessive fatigue (PD patients).A high prevalence of sleep disturbances in PD patients was found; this is to a large extent probably the result of aging. As compared with controls, patients had a more severely disturbed sleep maintenance because of nycturia, pain, stiffness, and problems with turning in bed. The prevalence of excessive dreaming is similar in both groups, but altered dream experiences almost exclusively occurred in PD.Patients rated themselves more often to be morning-types than controls. This finding may account for the reported adaptation effects in experimental settings and the reduced REM latency in PD patients.The prevalence of daytime sleepiness was similar in both groups. Excessive daytime sleepiness showed a clear diurnal pattern with a peak in the early afternoon. As for excessive fatigue, the majority of the patients did not report a preferential time for this symptom. Our findings further argue against an association of fatigue with any circadian factor, and instead suggest a relationship with the motor deficits of PD.

Juvenile Huntington disease.

SummaryOf 195 cases of juvenile Huntington disease gathered from case descriptions, the sex, age at onset, duration of disease, clinical type, sex of the affected parent, as well as sex, mean age at onset and at death of adult cases in the same pedigrees were noted when available, and the data were investigated for evidence of relationships between different features. Examination of a subset of 112 cases showed a preponderance of rigid cases, whose affected parent proved to be the father in a significantly high number of cases. Rigid paternal cases had a significantly lower age at onset, as well as a shorter duration of disease than choreatic paternal cases. No such relationship exists between rigid maternal and choreatic maternal cases. In rigid cases duration of disease proved to be shorter for those with a lower age at onset. Female juvenile cases tended to have a lower age at onset than male ones, regardless of clinical type or sex of the affected parent. The mean ages at onset and at death of adult members of the same pedigrees were not related to clinical type or age at onset of juvenile cases. It is argued that juvenile Huntington disease should not be regarded as a separate clinical entity, but as a manifestation of the rigid variant of the disease.

Clozapine versus placebo in Huntington’s disease: a double blind randomised comparative study

OBJECTIVES To establish the effect of the atypical neuroleptic clozapine on chorea, voluntary motor performance, and functional disability in patients with Huntington’s disease. METHODS Thirty three patients with Huntington’s disease participated in a double blind randomised trial. A maximum of 150 mg/day clozapine or placebo equivalent was given for a period of 31 days. Assessments were performed in the week before and at the last day of the trial. Chorea was scored using the abnormal involuntary movement scale (AIMS), the chorea score of the unified Huntington’s disease rating scale (UHDRS), and judgement of video recordings. Voluntary motor performance was assessed using the UHDRS motor scale. Patients and their partners completed a questionnaire regarding functional disability. Twelve patients already used other neuroleptic medication, which was kept unchanged during the trial period. Results of neuroleptic naive and neuroleptic treated patients were analysed separately. RESULTS Clozapine tended to reduce chorea in neuroleptic naive patients only (AIMS); improvement seemed more pronounced in patients receiving higher doses of clozapine. Other measures of chorea (UHDRS chorea score, video ratings) showed no improvement. Clozapine had no beneficial effect on chorea in patients already receiving neuroleptic medication. Voluntary motor performance did not improve with clozapine. Neuroleptic naive patients reported aggravation of functional disability, possibly reflecting the frequent occurrence of side effects. Adverse reactions forced trial termination in six patients and dose reduction in another eight, and consisted mainly of drowsiness, fatigue, anticholinergic symptoms, and walking difficulties. CONCLUSIONS Clozapine has little beneficial effect in patients with Huntington’s disease, although individual patients may tolerate doses high enough to reduce chorea. Because adverse reactions are often encountered, clozapine should be used with restraint in this patient group.

Cognition in patients with multiple sclerosis: After four years

This study reports on a 4-year follow-up of cognitive functioning in 33 MS patients and 18 healthy control subjects. As a group, and in agreement with the results in the previous assessment. MS patients have significantly weaker performances than controls in motor speed, reaction time, learning tasks, reading aloud and figure copying. Tasks addressing visuospatial problem solving, behavioural flexibility, and linguistic aspects of oral and written communication do not distinguish between the two groups. Influence of impaired movement is acknowledged in performances utilising speech and reading under instructions of speed, and in figure copying. Cognition per sé remained undisturbed in 25 patients (76%). A uniform MS-related development of cognitive deficits could not be identified, improvement, stability and further deterioration being found at reassessment.

Reproducibility of the mean power frequency of the surface electromyogram.

SummaryThere is evidence in the literature that the decrease of mean power frequency (MPF) during exercise is greater as a muscle becomes more fatigued. After strenuous exercise this phenomenon can last several days. It is usually assumed, however, that the MPF has a good reproducibility. In this study the reproducibility of the MPF of the surface electromyogram of the biceps brachii muscle was investigated for five subjects on 5 successive days. Force level, muscle length and skin temperature were kept constant. The results show that interindividual differences in MPF were large (SD 11.5 Hz). However, during these 5 days, the range in MPF for individual subjects was small. The SD of the trials within subjects and days was 2.0 Hz, while the SD of the days within subjects was 2.4 Hz (variability of the trials excluded). It is hypothesized that this SD may be due to variations in the electrode replacement. It is concluded that the variability in MPF for a subject is small compared to the decrease of the MPF associated with muscle fatigue and which can therefore be determined reliably during longitudinal studies.

Treatment of children with central precocious puberty by a slow-release gonadotropin-releasing hormone agonist.

A total of 82 patients (74 girls, 8 boys) are presently participating in an international multicentre trial for treatment of central precocious puberty (CPP) with a slow release gonadotropin-releasing hormone (GnRH) agonist depot preparation: Decapeptyl-Depot (DD). Of these patients, 53 (3 boys) were previously untreated (group 1) and 29 (5 boys) have been treated before with either a short-acting GnRH analogue or cyproterone acetate (group 2). Fifty-one patients (44 girls, 7 boys) were treated with DD for 12 months or more. Basal plasma luteinizing hormone (LH) levels decreased in both groups after 1 year of therapy. The LH response to intravenous GnRH was reduced in both groups. Basal plasma follicle stimulating hormone (FSH) levels decreased in both groups. Stimulated FSH levels were reduced in both groups after 1 year of DD treatment. Plasma oestradiol levels in the girls decreased to prepubertal levels in both groups. In all patients the clinical signs of precocious gonadarche such as breast development and menstruations (girls) and an increased testis volume (boys), did not further progress and sometimes regressed in several patients. Growth velocity decreased in the girls of group 1 from 9.0±0.72cm/year (mean±SEM) in the last half-year before treatment to 6.3±0.50 in the first half-year of treatment (P<0.01) and to 4.5±0.23 cm/year in the second half-year (P<0.01). After 12 months a stabilization of growth velocity was observed. The ΔBA/ΔCA ratio decreased during treatment in this group of girls, resulting in an improvement of adult height prediction from 161.9±3.3 cm (mean±SEM) at the start to 164.1±3.5cm after 18 months of therapy (P<0.05). No change of height prediction was observed in group 2. At present we consider one i.m. injection of DD every 4 weeks as the treatment of choice in children with CPP.

Enhanced susceptibility of low-density lipoproteins to oxidation in coronary bypass patients with progression of atherosclerosis

Oxidation of low-density lipoprotein (LDL) may play a causal role in atherosclerosis. In this study we analyzed whether the severity of progression of coronary atherosclerosis is related to the susceptibility of LDL to oxidative modification. On the basis of repeated coronary angiography, 28 coronary bypass patients were divided into two groups: group A, 12 patients with, and group B, 16 patients without progression of coronary atherosclerosis. The lag time, reflecting the resistance of LDL to oxidative modification, was significantly smaller in group A as compared with group B (81 +/- 10 and 93 +/- 15 min, respectively). Besides differences in cholesterol and apolipoprotein B concentrations, the difference in susceptibility of LDL to oxidation significantly contributes to the differences between the progression and the non-progression group (P = 0.02). In the combined groups of patients, the lag phase of LDL for oxidation was positively correlated with LDL cholesterol ester to protein ratio (r = 0.53, P = 0.01). It is concluded that LDL samples obtained from coronary bypass patients differ with respect to their oxidizability depending on progression of atherosclerosis following coronary bypass surgery.

Reaction time in ambulant multiple sclerosis patients

Reaction times (RT) were measured in 39 multiple sclerosis (MS) patients and 25 healthy controls, before and after comprehensive neuropsychological assessment lasting at least 4 h. The assessment required prolonged mental effort, which was assumed to induce fatigue. Simple and disjunctive RT were measured for visual and auditory stimuli. RT before and after prolonged effort were significantly longer in MS than in control subjects (with exception of auditory RT). This effect was related to disease duration and to simultaneous presence of brainstem, cerebellar and/or pyramidal signs. Age did not significantly contribute to the explanation of RT increase. In female patients, increasing distribution of functional lesions in the central nervous system was related with greater RT increase than in male patients. RT of MS and controls changed after prolonged mental effort and effort-related fatigue was experienced subjectively. Yet no differences in direction or degree of change in RT were found between controls and ambulant patients with stable MS who apparently had resources to overcome fatigue.

Respiration during sleep in Huntington's chorea

In view of recent reports on lower brainstem dysfunction in Huntingtons chorea, we studied respiration during sleep in 12 patients with Huntingtons chorea (HC) and in controls. There were no statistically significant differences between patients and controls with respect to apnea periods, respiratory frequency and time elapsed between minimal and maximal value of the respiratory curve. No statistically significant differences in respiratory variability were observed between patients and controls. In the present study, no indication was found for dysfunction of lower brainstem structures involved in respiration in HC.

The interrater reliability of a Dutch version of the comprehensive psychopathological rating scale

To apply the Comprehensive Psychopathological Rating Scale (CPRS) in the Netherlands we translated the English version into Dutch and examined its interrater reliability. Three patient groups were investigated. Kappa coefficients were generally comparable with those reported in a study of the German version of the CPRS and in a Dutch study measuring the present state by means of the Present State Examination.