René Dom

Cognitive changes in patients with Huntington's disease (HD) and asymptomatic carriers of the HD mutation--a longitudinal follow-up study.

Abstract.ObjectiveObjective information about the onset and progression of cognitive impairment in Huntington’s disease (HD) is very important in the light of appropriate outcome measures when conducting clinical trials. Therefore, we evaluated the progression of cognitive functions in HD patients and asymptomatic carriers of the HD mutation (AC) over a 2.5–year period.We also sought to detect the earliest markers of cognitive impairment in AC.MethodsA prospective study comparing HD patients, clinically asymptomatic HD mutation–carriers (AC) and non–carriers (NC). These groups were examined three times during a period of 2.5 years. At baseline the study sample consisted of 49 subjects. Forty–two subjects (19 HD patients, 12 AC and 11 NC) completed three assessments. A battery of neuropsychological tests measuring intelligence, attention, memory, language, visuospatial perception, and executive functions was performed.ResultsThe performance of HD patients deteriorated on the following cognitive tests: Symbol Digit Modalities Test (SDMT), Stroop Colour and Word, Boston Naming Test (BNT), Object and Space Perception and Trail Making Test–B. Longitudinal comparison of AC and NC revealed that performances on SDMT, Block Span, Digit Span Backwards, Hopkins Verbal Learning Test (learning and delayed recall) and Conditional Associative Learning Test are impaired in AC.ConclusionsTasks measuring mainly attention, object and space perception and executive functions adequately assess the progression of HD disease. Other cognitive functions do not significantly deteriorate. Furthermore, problems in attention, working memory, verbal learning, verbal long–term memory and learning of random associations are the earliest cognitive manifestations in AC.

Abnormalities of the spatiotemporal characteristics of gait at the onset of freezing in Parkinson's disease.

We investigated the spatiotemporal variables of gait leading up to freezing. Gait analysis was carried out on 14 patients with Parkinsons disease in the off phase of the medication cycle. A computerised, three‐dimensional gait analysis system was used to measure the walking pattern. After several trials of normal walking with voluntary stopping, distracting manoeuvres and obstacles on the walkway were used to provoke freezing or festination. The gait variables of normal (off phase), festinating, prestop, and prefreezing strides were analysed using analysis of variance for repeated‐measures. Cadence was excessively increased (68%) and stride length decreased (69%) during festination compared with normal off walking; a pattern which remained pronounced when comparing prefreezing strides with normal stopping. Analysing in more detail the three steps before a freeze, we found a progressive decrease of stride length and stable cadence rates and proportions of double support phases. The relationship between cadence and stride length exhibited an exponential increase of cadence with a decreasing stride length during festination and freezing. Results suggest that freezing is caused by a combination of an increasing inability to generate stride length superimposed on a dyscontrol of the cadence of walking.

Cognitive and behavioural effects of music-based exercises in patients with dementia

Objective: To evaluate the effect of a musical exercise programme on mood state and cognitive function in women with dementia. Design: Randomized controlled trial. Setting: Public Psychiatric Hospital Rekem, Belgium. Patients: Twenty-five patients with dementia. Interventions: Fifteen patients attended exercise training for three months, which consisted of daily physical exercises supported by music for 30 min/session. They were compared with a group of 10 control patients, who received an equal amount of attention through daily conversation. Main measures: The effect on cognition was measured by the Mini-Mental State Examination (MMSE) and the Amsterdam Dementia Screening Test 6 (ADS 6). Behaviour was evaluated with the abbreviated Stockton Geriatric Rating Scale (BOP scale). The assessments were made before, after six weeks of intervention and immediately after the three-month experimental period. Results: The exercise group showed a significant improvement in cognition. This was documented by an increased MMSE mean score of 12.87-15.53, and by a higher median score, rising from 10 to 14 points, on the subset ‘fluency’ (ADS 6 test). The control group showed no significant improvement, either on the MMSE (mean score of 10.80 -11.00) or on the fluency subtest of the ADS 6 (median scores were 6.5-7 points). The effects on behavioural changes were not significant. Conclusion: The present study suggests a beneficial effect of cognition using a music-based exercise programme in a group of patients with moderate to severe dementia. Further studies are needed to confirm these findings.

Creatine supplementation in Huntington’s disease A placebo-controlled pilot trial

Objective: To evaluate the effect of creatine (Cr) supplementation (5 g/day) in Huntington’s disease (HD). Methods: A 1-year double-blind placebo-controlled study was performed in 41 patients with HD (stage I through III). At baseline and after 6 and 12 months, the functional, neuromuscular, and cognitive status of the patients was assessed by a test battery that consisted of 1) the Unified Huntington’s Disease Rating Scale (UHDRS), 2) an exercise test on an isokinetic dynamometer to assess strength of the elbow flexor muscles, 3) a maximal exercise test on a bicycle ergometer to evaluate cardiorespiratory fitness, and 4) a test to assess bimanual coordination ability. Following the baseline measurements, the subjects were assigned to either a creatine (n = 26) or a placebo group (n = 15). Results: Scores on the functional checklist of the UHDRS (p < 0.05), maximal static torque (p < 0.05), and peak oxygen uptake (p < 0.05) decreased from the start to the end of the study, independent of the treatment received. Cognitive functioning, bimanual coordination ability, and general motor function (total motor scale, UHDRS) did not change from baseline to 1 year in either group. Conclusion: One year of Cr intake, at a rate that can improve muscle functional capacity in healthy subjects and patients with neuromuscular disease (5 g/day), did not improve functional, neuromuscular, and cognitive status in patients with stage I to III HD.

The use of rhythmic auditory cues to influence gait in patients with Parkinson's disease, the differential effect for freezers and non-freezers, an explorative study

Purpose. To study the effect of rhythmic auditory cues on gait in Parkinsons disease subjects with and without freezing and in controls. Method. A volunteer sample of 20 patients (10 freezers, 10 non-freezers) and 10 age-matched controls performed five randomized cued walking conditions in a gait-laboratory. Auditory cues were administered at baseline frequency, at an increased step frequency of 10 and 20% above baseline and at a decreased step frequency of 10 and 20% below baseline. Mean step frequency, walking speed, stride length and double support duration were collected. Results. Rhythmical auditory cueing induced speed changes in all subjects. Stride length was not influenced by rhythmical auditory cues in controls, whereas patients showed a larger stride length in the −10% condition (p < 0.01). Freezers and non-freezers showed the same response to rhythmical auditory cues. Within group analysis for stride length showed different cueing effects. Stride length decreased at the +10% condition for freezers (p < 0.05), whereas it increased for non-freezers. Conclusions. This study points to fact that physiotherapists might need to carefully adjust the cueing frequency to the needs of patients with and without freezing. On the basis of the present results we recommend to lower the frequency setting for freezers, whereas for non-freezers an increase of up to +10% may have potential therapeutic use.

A frequency and correlation analysis of motor deficits in Parkinson patients

PURPOSE The present study explored the frequency and pattern of functional motor problems of a group of Parkinson patients, as a first step towards developing a rational approach to rehabilitation intervention addressing the primary symptoms of the disease. METHOD Sixty patients, consisting of 40% women and 60% men with a mean age of 63.5 years and of which 88% were taking L-dopa, underwent a number of standardized clinical tests including part III of the UPDRS. They were also interviewed about the frequency of motor problems occurring at home. RESULTS Loss of trunk rotation as expressed in rolling in supine and reduced arm swing were the most frequently registered motor disorders (73%, 75%). Freezing at the start of, or during, walking was not observed during clinical testing but was frequently claimed to occur at home (48%, 23%). A broad spectrum of deficits regarding gait, posture, transfers and distal motor problems formed a cluster, which was strongly correlated with bradykinesia (p < 0.001). Principal component analysis identified four distinct problem areas: (1) axial motor performance; (2) akinetic gait problems; (3) rigidity; and (4) tremor. CONCLUSIONS Parkinson patients, particularly in the later stages of the disease, presented with significant levels of functional disability which was mainly linked with the underlying impairment of bradykinesia.

Prediction of psychological functioning one year after the predictive test for Huntington's disease and impact of the test result on reproductive decision making.

For people at risk for Huntingtons disease, the anxiety and uncertainty about the future may be very burdensome and may be an obstacle to personal decision making about important life issues, for example, procreation. For some at risk persons, this situation is the reason for requesting predictive DNA testing. The aim of this paper is two-fold. First, we want to evaluate whether knowing ones carrier status reduces anxiety and uncertainty and whether it facilitates decision making about procreation. Second, we endeavour to identify pretest predictors of psychological adaptation one year after the predictive test (psychometric evaluation of general anxiety, depression level, and ego strength). The impact of the predictive test result was assessed in 53 subjects tested, using pre- and post-test psychometric measurement and self-report data of follow up interviews. Mean anxiety and depression levels were significantly decreased one year after a good test result; there was no significant change in the case of a bad test result. The mean personality profile, including ego strength, remained unchanged one year after the test. The study further shows that the test result had a definite impact on reproductive decision making. Stepwise multiple regression analyses were used to select the best predictors of the subjects post-test reactions. The results indicate that a careful evaluation of pretest ego strength, depression level, and coping strategies may be helpful in predicting post-test reactions, independently of the carrier status. Test result (carrier/ non-carrier), gender, and age did not significantly contribute to the prediction. About one third of the variance of post-test anxiety and depression level and more than half of the variance of ego strength was explained, implying that other psychological or social aspects should also be taken into account when predicting individual post-test reactions.

α2-macroglobulin expression in neuritic-type plaques in patients with Alzheimer's disease

Because it has been suggested that alpha 2M could be involved in the generation of amyloid peptide, attention was given to a possible association of alpha 2M expression and amyloid accumulation in the brain. Therefore, we investigated the presence of the proteinase inhibitor alpha 2-macroglobulin (alpha 2M) in the cerebra of 4 patients with Alzheimers Disease (AD). One case of a patient with Downs syndrome, 2 cases of patients with Dementia of the Lewy Body type (DLB), 1 case of an aged, clinically nondemented person who displayed many amyloid plaques, and 3 normal aged control brains were also studied. The results obtained by immunocytochemistry with monoclonal antibodies directed against two different epitopes of human alpha 2M showed an association of alpha 2M, only with neuritic-type plaques in patients with AD. No alpha 2M immunoreactivity was found in either preamyloid-type plaques or burned out-type plaques in AD, DLB, or aged nondemented controls. The results do not support a direct role of this proteinase inhibitor in the formation of amyloid. Because alpha 2M is observed to be associated with reactive microglia in the outer border of the neuritic plaques, the data suggest that alpha 2M could be a marker for an inflammatory cellular process in these neuritic plaques.

Neuropathology of Huntington's chorea Studies of the ventrobasal complex of the thalamus

In seven cases of Huntingtons chorea, the ventrolateral thalamus was studied by quantitative cytometry. A selective 50 percent atrophy of microneurons (internuncial cells) was found while the macroneurons did not show significant atrophy. Thalamic microneurons might be presynaptic and postsynaptic inhibitory cells. Their specific atrophy in Huntingtons chorea thus could be related to the known decrease of gamma aminobutyric acid (GABA) in Huntingtons chorea.

Innervation of rabbit intrapulmonary neuroepithelial bodies: Quantitative and qualitative ultrastructural study after vagotomy☆

The purpose of this study was to locate the cell bodies of origin of the intracorpuscular nerve endings of the intrapulmonary neuroepithelial bodies (NEB). Left infra- or supranodosal vagotomy was performed on 35 young rabbits. In control animals, the NEB innervation index (i.e. the ratio of the number of intracorpuscular nerve endings to the number of NEB corpuscular epithelial cells) was 0.3 in both left and right lungs. Left infranodosal vagotomy decreased the NEB innervation index in the left lung to 0.1 by 24 h postoperatively. Degenerating nerve endings displaying neurofilamentous hyperplasia, were found among the few surviving nerve endings. Left supranodosal vagotomy did not influence the innervation of the NEB of the left lung, even at 5 days postoperatively. In the right lungs, neither procedure had significant effects. These findings indicate that the NEB are predominantly innervated by sensory nerve fibers, derived from cell bodies in the nodose ganglion of the vagus nerve. This neuroanatomical argument corroborates our hypothesis that NEB represent intrapulmonary neuroreceptors.