Video documented follow-up of liver transplantation in Wilson's disease with predominant neurological manifestation.

Wilson's disease (WD) is a rare autosomal-recessive disorder of copper metabolism with predominantly hepatic and extrapyramidal motor symptoms. Copper chelating therapy has proven to be an effective treatment for WD. Yet, if conservative treatment fails, liver transplantation (LT) often is the only remaining therapeutic option. The indication for LT especially in patients with stable liver function but severe neurological manifestation is debated controversially. In this case report, we document the follow up of neurological symptoms in WD after LT for the first time on video.

Delta 9-tetrahydrocannabinol (THC) is effective in the treatment of tics in Tourette syndrome: a 6-week randomized trial.

BACKGROUND: Preliminary studies suggested that delta-9-tetrahydrocannabinol (THC), the major psychoactive ingredient of Cannabis sativa L., might be effective in the treatment of Tourette syndrome (TS). This study was performed to investigate for the first time under controlled conditions, over a longer-term treatment period, whether THC is effective and safe in reducing tics in TS. METHOD: In this randomized, double-blind, placebo-controlled study, 24 patients with TS, according to DSM-III-R criteria, were treated over a 6-week period with up to 10 mg/day of THC. Tics were rated at 6 visits (visit 1, baseline; visits 2-4, during treatment period; visits 5-6, after withdrawal of medication) using the Tourette Syndrome Clinical Global Impressions scale (TS-CGI), the Shapiro Tourette-Syndrome Severity Scale (STSSS), the Yale Global Tic Severity Scale (YGTSS), the self-rated Tourette Syndrome Symptom List (TSSL), and a videotape-based rating scale. RESULTS: Seven patients dropped out of the study or had to be excluded, but only 1 due to side effects. Using the TS-CGI, STSSS, YGTSS, and video rating scale, we found a significant difference (p <.05) or a trend toward a significant difference (p <.10) between THC and placebo groups at visits 2, 3, and/or 4. Using the TSSL at 10 treatment days (between days 16 and 41) there was a significant difference (p <.05) between both groups. ANOVA as well demonstrated a significant difference (p =.037). No serious adverse effects occurred. CONCLUSION: Our results provide more evidence that THC is effective and safe in the treatment of tics. It, therefore, can be hypothesized that the central cannabinoid receptor system might play a role in TS pathology.

Disturbed monitoring and response inhibition in patients with Gilles de la Tourette syndrome and co-morbid obsessive compulsive disorder.

OBJECTIVE: Fronto-striatal dysfunction has been discussed as underlying symptoms of Tourette syndrome (TS) with co-morbid Obsessive Compulsive Disorder (OCD). This suggests possible impairments of executive functions in this disorder, which were therefore targeted in the present study. METHODS: A comprehensive series of neuropsychological tests examining attention, memory and executive functions was performed in a group of 14 TS/OCD in co-occurrence with OCD patients and a matched control group. RESULTS: While attentional and memory mechanisms were not altered, TS/OCS patients showed deficits in executive functions predominantly in the areas of response inhibition and action monitoring. CONCLUSIONS: These findings provide further evidence for a substantial impairment of the frontal-striatal-thalamic-frontal circuit. We propose that the deficits in monitoring, error detection and response inhibition constitute the major impairment of TS/OCD patients in the cognitive domain.

Treatment of Tourette syndrome with delta-9-tetrahydrocannabinol (delta 9-THC): no influence on neuropsychological performance.

Previous studies provide evidence that marijuana (Cannabis sativa) and delta-9-tetrahydrocannabinol (Delta(9)-THC), the major psychoactive ingredient of marijuana, respectively, are effective in the treatment of tics and behavioral problems in Tourette syndrome (TS). It, therefore, has been speculated that the central cannabinoid receptor system might be involved in TS pathology. However, in healthy marijuana users there is an ongoing debate as to whether the use of cannabis causes acute and/or long-term cognitive deficits. In this randomized double-blind placebo-controlled study, we investigated the effect of a treatment with up to 10 mg Delta(9)-THC over a 6-week period on neuropsychological performance in 24 patients suffering from TS. During medication and immediately as well as 5-6 weeks after withdrawal of Delta(9)-THC treatment, no detrimental effect was seen on learning curve, interference, recall and recognition of word lists, immediate visual memory span, and divided attention. Measuring immediate verbal memory span, we even found a trend towards a significant improvement during and after treatment. Results from this study corroborate previous data suggesting that in patients suffering from TS, treatment with Delta(9)-THC causes neither acute nor long-term cognitive deficits. Larger and longer-duration controlled studies are recommended to provide more information on the adverse effect profile of THC in patients suffering from TS.

[N-methyl 11C]meta-Hydroxyephedrine positron emission tomography in Parkinson's disease and multiple system atrophy.

Orthostatic hypotension (OH) can be present in idiopathic Parkinson's disease (IPD) as well as in atypical parkinsonian syndromes such as multiple system atrophy (MSA). According to clinical tests of sympathetic nerve function and histopathological data, OH is caused by primarily postganglionic sympathetic dysfunction in IPD and by predominantly central and preganglionic degeneration in MSA. It has been proposed that this concept of a different underlying pathogenesis for OH should be applied in the differential diagnosis of parkinsonian disorders, in the form of measurements of sympathetic myocardial innervation. In this pilot study, myocardial imaging with [ N-methyl (11)C]meta-hydroxyephedrine ((11)C-HED) and positron emission tomography (PET) was used as a quantitative tool to evaluate the feasibility of such an approach. Seven patients were included in the study. Two had MSA and OH, three had probable IPD and OH (duration of disease, >3 years), one had probable IPD without OH (disease duration, 3 years) and one had possible IPD without OH (disease duration, 2 years). Ratios of maximal (11)C-HED uptake in the myocardium to that in the liver at 5 and 40 min post injection (p.i.) and - based on kinetic modelling - tracer influx rates K(1) were calculated. Compared with MSA patients ( n=2), IPD patients with OH ( n=3) showed definitely lower uptake ratios at both 5 min p.i. (0.39-0.57 vs 0.78-0.79) and 40 min p.i. (0.21-0.60 vs 0.89-1.06), as well as lower K(1) values (0.198-0.359 vs 0.384-0.450 min(-1)). The patient with probable IPD without OH showed intermediate values (uptake ratio at 5 min: 0.65; uptake ratio at 40 min: 0.87; K(1)=0.363). In the patient with possible IPD, values (uptake ratio at 5 min: 0.96; uptake ratio at 40 min: 1.04; K(1)=0.400) did not differ from those observed in MSA. These results support the hypothesis that measurement of myocardial innervation may contribute to the differential diagnosis of parkinsonian disorders and suggest a need for quantitative pathophysiological imaging, particularly at early stages of disease.

Disturbance of "extrinsic alertness" in Huntington's disease.

Neuropsychological deficits are a main feature of Huntington's disease (HD) with previous data suggesting involvement of attentional functions. Attention can be divided into several different dimensions: intensity, selectivity and supervisory attentional control. These different aspects of attention were investigated in a group of 13 patients with HD and 13 healthy matched control subjects. HD patients were impaired mostly for the intensity dimension: contrary to controls, and like other neurological patient groups, they were not able to speed up their reaction times when an auditory warning stimulus preceded a visual target which suggests a deficit in 'extrinsic alertness.' In addition less severe impairments were found in the dimensions selectivity and supervisory attentional control.