Biomedical subjects

Werner Poewe

Publications and source records attributed to Werner Poewe.

98 records · Page 6Linked to original sources

PubMed2002

Early consolidation in human primary motor cortex.

Behavioural studies indicate that a newly acquired motor skill is rapidly consolidated from an initially unstable state to a more stable state, whereas neuroimaging studies demonstrate that the brain engages new regions for performance of the task as a result of this consolidation. However, it is not known where a new skill is retained and processed before it is firmly consolidated. Some early aspects of motor skill acquisition involve the primary motor cortex (M1), but the nature of that involvement is unclear. We tested the possibility that the human M1 is essential to early motor consolidation. We monitored changes in elementary motor behaviour while subjects practised fast finger movements that rapidly improved in movement acceleration and muscle force generation. Here we show that low-frequency, repetitive transcranial magnetic stimulation of M1 but not other brain areas specifically disrupted the retention of the behavioural improvement, but did not affect basal motor behaviour, task performance, motor learning by subsequent practice, or recall of the newly acquired motor skill. These findings indicate that the human M1 is specifically engaged during the early stage of motor consolidation.

Adult↗

PubMed2002

Parkinsonism in multiple system atrophy: natural history, severity (UPDRS-III), and disability assessment compared with Parkinson's disease.

We analyzed parkinsonian features in multiple system atrophy (MSA) compared with age- and disease duration-matched Parkinson's disease (PD) patients, and assessed the applicability of the Unified Parkinson's Disease Rating Scale (UPDRS) -III motor scale as a means of rating their severity. Cross-sectional analysis of parkinsonism was done using UPDRS-III, International Cerebellar Atatia Rating Scale, and disability scales (Hoehn and Yahr [H&A], Schwab and England, Katz and Lawton) in 50 unselected MSA patients and in 50 matched PD patients. At symptom onset, falls occurred 10 times more frequently in MSA, whereas limb tremor was 10 times more common in PD. At first visit (10.2 months), hemiparkinsonism and pill-rolling rest tremor were less common in MSA. Hypomimia, atypical rest, postural or action tremor, as well as postural instability were more frequent in MSA. At study examination (62.4 months), parkinsonian signs in MSA patients were more frequently symmetrical and associated with axial rigidity, antecollis and postural instability. A levodopa response of >50% was seen in <10% of MSA patients. Modified H&Y stages (3.2 +/- 1.3 vs. 2.2 +/- 0.78) and UPDRS-III scores (48.14 +/- 19.5 vs. 31.74 +/- 12.9) were significantly (P = 0.0001) higher in MSA. The internal consistency of the UPDRS-III was fair in MSA patients (Cronbach's alpha >0.90), and correlated well with marked dependency on the Schwab and England and Katz and Lawton scales. Factor structure analysis of UPDRS-III in MSA showed five clinically distinct subscores accounting for 74% of the variance, differing from PD by the dependency of the face-speech and limb bradykinesia items and independence of the postural-action tremor from the rest tremor items. There was a significant correlation (R(2) = 0.70, P = 0.001) between ICARS ataxia and UPDRS-III scores in MSA patients. Results confirm a distinct profile of parkinsonism in MSA and greater severity and disability compared with PD. It also indicates that the UPDRS-III provides a useful severity measure of parkinsonism in MSA, albeit contaminated by additional cerebellar dysfunction.

Activities of Daily Living↗

PubMed2002

Freezing of gait in postmortem-confirmed atypical parkinsonism.

The frequency and pathophysiology of freezing of gait (FoG) in atypical parkinsonism is unknown. We analysed the frequency of FoG in postmortem-confirmed atypical parkinsonian disorders (APD) comprising corticobasal degeneration (CBD), dementia with Lewy bodies (DLB), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). Sixty-six patients with pathologically confirmed APD (CBD, n = 13; DLB, n = 14; MSA, n = 15; PSP, n = 24) formed the basis for a multicenter clinicopathological study. Clinical features at first and last clinical visit were abstracted from patient records on standardized forms following strict instructions. At the first visit (median 36 months after symptom onset), 24% of APD had FoG (CBD, 8%; DLB, 21%; PSP, 25%; MSA, 40%). Logistic regression analysis showed a significant association of FoG and urinary incontinence (P = 0.04) at first visit. At last visit, 47% of APD had FoG (CBD, 25%; PSP, 53%; DLB, 54%; MSA, 54%). Clinicopathological correlation based on routine postmortem examination failed to identify a consistent neuropathological substrate of FoG. This study demonstrates that (1) FoG is common in APD, and (2) urinary incontinence is significantly associated with FoG in these disorders. Whether FoG and urinary incontinence share similar neuropathological substrates remains to be determined by future studies.

Aged↗

PubMed2002

Application of the International Cooperative Ataxia Scale rating in multiple system atrophy.

We assessed the International Cooperative Ataxia Scale (ICARS) as a means of extracting and rating cerebellar signs in multiple system atrophy (MSA). Cross-sectional analysis of internal consistency, factor structure, and correlation with parkinsonism severity (Unified Parkinson's Disease Rating Scale [UPDRS] III) of the ICARS, in 50 unselected MSA patients (mean age, 67.6 years; mean disease duration, 5.5 years), 50 age-matched and disease duration-matched Parkinson' disease (PD) patients, and 50 control subjects. Fifteen patients (30%) had MSA-C (cerebellar subtype) and 35 (70%) MSA-P (parkinsonism subtype), and 66% had at least one cerebellar sign. The total ICARS score was much higher (fivefold) in MSA compared to PD patients. The ICARS score was twofold higher in MSA-C than in MSA-P patients. MSA-C patients had a higher score than MSA-P mainly on posture and gait disturbances and kinetic functions subscores. All the ICARS items were significantly more severe in MSA than in PD patients, who in turn scored higher than the controls. In MSA, internal consistency was excellent (Cronbach = 0.93). Factor structure analysis revealed four clinically distinct subscores, in accordance with the scale structure, which accounted for 70% of the variance. The ICARS showed less consistency and accuracy in PD patients; however, the ICARS scores significantly correlated with the UPDRS-III scores in both MSA and PD patients. The ICARS appears a useful tool to extract and rate the severity of cerebellar signs in MSA; however, it is clearly contaminated by parkinsonian features.

Aged↗

PubMed2002

Riluzole therapy in cervical dystonia.

We conducted a 6-week open-label pilot study with blinded video rating of riluzole (50 mg twice a day) in six patients with cervical dystonia (CD) refractory to botulinum toxin A and oral pharmacological treatment. The Tsui rating scale served as primary efficacy measure and improved significantly under riluzole (P = 0.002). In three of six patients, the Tsui score improved by more than 30% with a greater 50% reduction in the head tremor/jerk subscore of the Tsui scale. These data suggest that riluzole may be helpful in a subgroup of patients with disabling CD refractory to other therapies.

Adult↗

PubMed2002

Evaluation of striatal dopamine transporter function in rats by in vivo beta-[123I]CIT pinhole SPECT.

Striatal dopamine transporter (DAT) function was evaluated in rats by in vivo SPECT-MRI coregistration using the radioligand 2-beta-carbomethoxy-3-beta-(4-[123I]iodophenyl)tropane (beta-[123I]CIT). The reconstructed transaxial resolution of 3.5 mm full width at half-maximum and the system sensitivity of 0.081 c/s/kBq using a 2.0-mm pinhole collimator aperture provided adequate spatial detail and sufficient sensitivity for imaging striatal beta-[123I]CIT uptake. SPECT images, coregistered onto a MRI template, showed high accuracy in the coronal and transverse planes (maximum mismatch of 1.3 mm). Following estimation of the in vivo binding equilibrium of beta-[123I]CIT in the healthy rat striatum, we evaluated the 6-hydroxydopamine-induced loss of striatal DAT function using beta-[123I]CIT SPECT and MRI coregistration and correlated these findings with dopaminergic cell counts in the substantia nigra pars compacta using TH immunohistochemistry. A subtotal unilateral DAT deficit was detected by beta-[123I]CIT SPECT in all animals which correlated significantly with the cell counting of the remaining dopaminergic neurons. beta-[123I]CIT pinhole SPECT provides a powerful and widely available tool for in vivo investigations of rat striatal DAT function. In contrast to classical autoradiography, the present method will be helpful in imaging dynamic changes of neurotransmission in the CNS by virtue of serial study designs. Depending on SPECT ligand availability, a wide range of other CNS receptors may be imaged as well using the presented in vivo technique.

Animals↗

PubMed2002

Low concentrations of STI571 in the cerebrospinal fluid: a case report.

We report a 53-year-old man with lymphoid blast crisis of Ph+ chronic myeloid leukaemia who was treated with STI571, a selective inhibitor of the enzymatic activity of BCR-ABL. He responded excellently to STI571 (600 mg/d), obtaining a complete cytogenetic remission after 3 months of therapy. Although remission in the bone marrow was sustained, the patient developed an isolated central nervous system relapse. Subsequent analyses of STI571 concentrations in the cerebrospinal fluid (CSF) revealed 2-log lower CSF levels of STI571 than corresponding plasma levels. These are the first data demonstrating a low penetration of orally administered STI571 into the CSF in humans.

Antineoplastic Agents↗

PubMed2002

Active and passive smoking, chronic infections, and the risk of carotid atherosclerosis: prospective results from the Bruneck Study.

BACKGROUND AND PURPOSE: Susceptibility of the vasculature to the injurious effects of smoking varies substantially, with some smokers developing severe premature atherosclerosis and others remaining free of advanced atheroma until high ages. The present study sought to estimate the contribution of chronic infections to the variability of atherosclerosis severity among smokers. METHODS: In the community-based Bruneck Study, 5-year changes in carotid atherosclerosis were assessed by high-resolution ultrasound. Early atherogenesis was defined by the development of nonstenotic plaques and advanced atherogenesis by the development/progression of vessel stenosis >40%. RESULTS: The risk of early atherogenesis strongly relied on lifetime smoking exposure and remained elevated long-term after cessation of smoking. Remarkably, current and ex-smokers faced an increased atherosclerosis risk only in the presence of chronic infections (odds ratios [95% CIs], 3.3 [1.8 to 6.2] and 3.4 [1.8 to 6.3]; P<0.001 each), whereas current, past, and nonsmokers without infections did not differ substantially in their estimated risk burden (odds ratios [95% CIs], 1.4 [0.8 to 2.4], 0.9 [0.6 to 1.6], and 1.0 [reference group]). In analogy to first-hand smoking, subjects exposed to environmental tobacco smoke were found to be vulnerable to the manifestation of chronic infection, and only those infected experienced a high atherosclerosis risk. The risk of advanced atherogenesis showed a dose-response relation with the number of daily cigarettes, returned to normal shortly after cessation of smoking, and emerged as independent of infectious illness. CONCLUSIONS: Our study provides the first epidemiological evidence that the proatherogenic effects of cigarette smoking are mediated in part by the chronic infections found in smokers. A better understanding of the vascular pathogenetic mechanisms of smoking may offer novel clues for disease prevention supplementary to the primary goal of achieving long-term abstinence.

Adult↗