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Evidence for the extent and nature of attentional impairment in premanifest and manifest Huntington’s disease (HD) is inconsistent. Understanding such impairments may help to better understand early functional changes in HD and could have consequences concerning care for HD patients. We investigated attentional control in both early and premanifest HD. We studied 17 early HD subjects (mean age: 51 years), 12 premanifest HD subjects (mean age: 43 years), and 15 healthy controls (mean age: 51 years), using the sustained attention to response task (SART), a simple Go/No-go test reflecting attentional and inhibitory processes through reaction time (RT) and error rates. Simultaneously recorded EEG yielded P300 amplitudes and latencies. The early HD group made more Go errors (p

De ziekte van Parkinson is een veelvoorkomende ziekte. Het is een chronisch progressieve aandoening gekenmerkt door tremoren, stijfheid van spieren en/of bradykinesie, waardoor de betrokkene in werk en in het priveleven toenemend gehinderd wordt. De ziekte openbaart zich meestal op middelbare leeftijd (tussen de 40 en 60 jaar), maar begint bij een klein aantal patienten al voor het veertigste jaar. Naar schatting zijn er in Nederland ongeveer 45.000 patienten. De prevalentie is 10 per 100.000 bij mensen onder de 50 jaar, maar loopt op tot 600 per 100.000 boven de 65. De incidentie bedraagt voor mannen en vrouwen gelijk 10 per 100.000.

Plaque-like lesions and amyloid angiopathy were investigated in the frontal cerebral cortex of four patients with hereditary cerebral hemorrhage with amyloidosis (Dutch) (HCHWA-D), using immunohistochemical [antibodies to beta amyloid protein (A beta), beta protein precursor (beta PP), synaptophysin, ubiquitin (UBQ), cathepsin D, paired helical filaments (PHF) and glial fibrillary acidic protein (GFAP)], enzymehistochemical (acid phosphatase) and silver [methenamine silver (MS) and Palmgren] staining methods. Whereas A beta- and MS-positive diffuse plaques were found in all patients, only the three older patients showed neuritic or congophilic plaques, which were acid phosphatase and cathepsin D positive and contained beta PP-, synaptophysin- and UBQ-positive, but PHF-negative neurites. These plaques were surrounded by reactive astrocytes. Similar immuno- and enzymereactivity was found around congophilic blood vessels. Thus, apart from neuronal degeneration in a subset of plaque-like lesions and around blood vessels, this study shows an age-related morphology of the plaques in HCHWA-D, corresponding to that in Down's syndrome (DS), with the difference that neurofibrillary (NF) pathology is absent in HCHWA-D in contrast to DS. HCHWA-D may be considered as a model for congophilic plaque formation not associated with NF pathology.

In this study we evaluate the feasibility of measures that reflect different characteristics of motor activity and immobility in the objective quantification of hypokinesia. Because by definition hypokinesia can only be assessed over a period of time, continuous activity monitoring was used during 5 successive days in the home setting in 64 patients with Parkinson's disease (PD) and 104 healthy elderly subjects. In the patients we also evaluated the relation between the monitor measures and subjective measures of hypokinesia and age. Compared to the healthy elderly subjects, PD patients have a decreased activity level, increased proportion of time without movement, elevated mean duration of immobility, and decreased percentage of short-lasting immobility periods. Differences between both groups were most prominent for those measures that incorporate or reflect immobility. Moreover, in the PD patients the mean duration of immobility and percentage of short-lasting immobility periods show an apparent lack of relation with age and clinical ratings obtained from the UPDRS. In conclusion, our findings underscore the poor representation of hypokinesia in the UPDRS and value of objective quantification of this fundamental impairment of PD.

The objective of this questionnaire-based survey was to evaluate the prevalence and causes of sleep disturbances in 90 nondepressive patients with Parkinson's 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.

Aangenomen wordt dat dwangneurose vaak voorkomt bij patienten met het syndroom van Gilles de la Tourette (GTS). Fenomenologische analyse van de dwangverschijnselen bij GTS–patienten laat echter zien dat het gaat om egosyntone impulsen. Deze symptomen zijn meer verwant aan stoornissen in de impulscontrole (en aan GTS) dan aan de obsessiefcompulsieve stoornis.

We studied the presence and morphology of plaque-like lesions in the frontal cortex of six patients, aged 40 to 76 years, with hereditary cerebral hemorrhage with amyloidosis--Dutch type (HCHWA-D), using beta/A4 immuno-, silver, Congo red and thioflavin S staining. Two types of beta/A4 immunoreactive and Congo red-negative plaques were detected. The first type was composed of argyrophilic fibrous material in periodic acid-methenamine silver (PAM) and modified Bielschowsky staining and lacked silver-stained degenerating neurites. Therefore, this type of plaque has the same staining properties as the diffuse plaque described in Alzheimer's disease, Down's syndrome and nondemented elderly. The second type of plaque, occurring only in the three oldest patients and numerically increasing with age, consisted of a spherical non-argyrophilic area of granular texture with a rim of PAM-positive material. The PAM-positive fibrous material of both types of plaques was mingled with coarser and compact, irregular-shaped argyrophilic structures in the oldest patient. The described plaques did not show bright fluorescence with thioflavin S staining. These results indicate, that the morphology of plaques, encountered in HCHWA-D, is diverse and changes with age.

Background TRACK-HD is a multi-center, longitudinal study investigating a range of motor, cognitive, neuropsychiatric, and imaging measures as potential biomarkers for clinical trials in Huntington's disease (HD). Psychiatric assessments were conducted using a 10-item semi-structured interview, the short version of the Problem Behaviours Assessment for HD (PBA-s). Interviews were video recorded for quality assurance purposes, and a proportion randomly selected for re-scoring at another site. The study therefore provided an opportunity to examine the reliability of the measure between multiple pairs of raters in different cultural and linguistic contexts. Methods The study included 360 subjects (120 affected, 120 premanifest gene carriers, 120 controls), and 185 interviews were selected for re-scoring by an expert rater. Digital video recordings were uploaded to the TRACK-HD Web portal and selected for re-scoring by an independent investigator blind to the subjects' diagnosis. A further 73 interviews were obtained from the REGISTRY clinic in Manchester and used for training the expert raters. Results Complete agreement between raters was achieved for 86% of scores (κ = 0.733), and 97.6% were within one point of the expert rating, the standard for quality assurance purposes. Agreement levels for individual pairs of raters ranged from 75% to 94% (κ = 0.59–0.86); agreement within one point ranged from 92% to 99%. Complete agreement for the 20 individual ratings (10 symptoms * frequency and severity) ranged from 67% to 100% (κ = 0.56–0.97); agreement within one point ranged from 94% to 100%. Conclusions The overall results indicate substantial agreement between all raters, whereas the κ-statistic for individual rater pairs ranged from ‘moderate' to ‘almost perfect' agreement, with almost all raters achieving at least a ‘substantial' level of agreement. These data suggest that the PBA-s, with appropriate training, is a reliable measure of psychiatric symptoms in the HD population.

Background TRACK-HD is a multi-center, longitudinal study investigating a range of motor, cognitive, neuropsychiatric, and imaging measures as potential biomarkers for clinical trials in Huntington's disease (HD). Psychiatric assessments were conducted using a 10-item semi-structured interview, the short version of the Problem Behaviours Assessment for HD (PBA-s). To better characterize the relationship between scores on individual PBA items and overall severity of behavioral symptoms, a nonparametric item response analysis (Ramsay JO, Psychometrika 1991;56:611–630) was performed on the data from year 1 of the study. Methods The study included 366 subjects (123 affected, 123 premanifest gene carriers, 120 controls). Option Characteristic Curves (OCCs) were generated for all PBA-s items to determine the probability of scoring a particular option in relation to total PBA score. Results Most items, including Depressed Mood, Anxiety, Irritability, Aggressive Behavior, and Apathy showed generally good discriminative properties, but differences were observed between the three populations (affected, pre-manifest, and control subjects) in terms of their IRT curves. Suicidality was primarily endorsed at the higher levels of overall severity and did not discriminate well at lower PBA scores. A number of symptoms were rarely endorsed in this population at any level of overall behavioral symptom severity, including Delusions, Hallucinations and Disorientation. Conclusions These results demonstrate that some items on the PBA-s are more sensitive than others in capturing the overall severity of behavioral symptoms in early and pre-manifest HD, and thus may be more suitable to provide a reliable and valid measure of behavioral symptoms in this population.

A device for quantification of involuntary body movements is described. Patients are situated within the low-intensity radiation beam of a Doppler radar motion transducer. This device converts all body movements into one electrical signal which contains information on the size and trajectory of the moving parts of the body. This signal is processed in such a way that the obtained ‘quantity of motion’ Q within a certain period is proportional to the number of movements, the length of their trajectory and the size of the involved parts of the body. Therefore the obtained parameter is closely related to the burden that the movements exert on the patient. The low-cost device is very simple to apply and the results are online available.

Cervical laminectomy was performed in a 34-year-old man with multiple spinal neurofibromas because of a slowly progressive medullary compression. Four weeks later a rapid deterioration necessitated iopamidol myelography by left lateral cervical puncture at C2 level. Despite the establishment of adequate spinal fluid contact, resulting in imaging of the subarachnoid space, part of the contrast medium entered the spinal cord, thus delineating a syrinx from the upper cervical extending to the upper thoracic level. After the puncture the patient developed triplegia, involving the left arm and both legs and a paresis of the right arm. He died from aspiration pneumonia. Autopsy revealed haemorrhagic necrosis of the spinal grey matter. This adverse effect of myelography is argued to have been conditioned by the extreme immobility and displacement of the spinal cord due to the presence of multiple neurofibromas. The deterioration four weeks after the operation was probably caused by a further compression of the spinal cord.