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Werner Poewe

Publications and source records attributed to Werner Poewe.

At least 55 records · Page 3Linked to original sources
PubMed2005

Evidence for dopaminergic re-innervation by embryonic allografts in an optimized rat model of the Parkinsonian variant of multiple system atrophy.

Embryonic transplantation has been considered as an alternative treatment strategy for drug resistant parkinsonian symptoms in multiple system atrophy. So far our group has created a number of animal models of striatonigral degeneration, the core pathology underlying progressive Parkinsonism associated with multiple system atrophy, as testbed for neurorestaurative and neuroprotective approaches. Using embryonic allografts of either nigral, striatal, or combined nigro-striatal tissue we were able to consistently show graft survival in a denervated and lesioned striatum as well as improvement of rotational behaviour. However, due to severe lesions of the striatum and the chosen time window of 3-6 weeks between lesion and grafting, severe gliosis led to demarcation of the graft and prevented re-innervation of the remaining adult striatum. The aim of the present study was to modify our "double toxin-double lesion" rat model by reducing the dose of quinolinic acid injected into the striatum from 150 to 75 nmol and shortening the interval between lesion and grafting to 1-2 weeks. Injection of 75 nmol quinolinic acid still led to a significant reduction of DARPP-32 positive neurons and volume in the striatum. Analysis of embryonic mesencephalic grafts revealed survival of dopaminergic neurons and outgrowth of fibres re-innervating the adult striatum. Rotation behaviour was improved in the graft group. Considering embryonic transplantation a possible future antiparkinson therapeutic intervention in multiple system atrophy patients our data stress the necessity of optimal patient selection, i.e. early stage disease with limited striatal dysfunction.

Amphetamine↗
PubMed2005

Daytime sleepiness is not increased in mild to moderate multiple sclerosis: a pupillographic study.

BACKGROUND: Daytime sleepiness has been described in multiple sclerosis (MS); a combination of MS and narcolepsy has also been observed in a few case reports. In this study, we investigated daytime sleepiness in a general sample of MS patients compared to healthy controls with the pupillographic sleepiness test (PST) and the Epworth and Stanford sleepiness scales (ESS, SSS). METHODS: A PST was performed in consecutive MS patients and controls. Additionally, a questionnaire including the ESS and the SSS was applied. RESULTS: Sixty-one MS patients (29 men and 32 women, age 34.5+/-8.3 years, mean disease duration 7.4+/-6.6 years, expanded disability status scale (EDSS) 1.7+/-1.2 (mean +/- sd)) and 42 age-matched controls (13 men and 29 women, age 36.9+/-12.9 years) participated in this study. In the MS group, the pupillary unrest index (PUI) was 5.0+/-2.0, the ESS 7.4+/-3.5 and the SSS 2.4+/-1.2, whereas in the control group, the PUI was 4.7+/-1.8, the ESS 8.4+/-4.0 and the SSS 2.4+/-1.2 (mean +/- sd). These differences were not significant. No correlation was found between PUI and the ESS or the SSS. Furthermore, no correlation was found between EDSS and sleepiness measured by PUI, ESS and SSS. CONCLUSION: In a general sample of MS patients with mild to moderate disease, there was no evidence for overall increased daytime sleepiness compared to healthy controls.

Adult↗
PubMed2005

Voxel-based morphometry in narcolepsy.

BACKGROUND AND PURPOSE: Voxel-based morphometry (VBM) is a magnetic resonance imaging (MRI)-based indirect volumetry, which allows the investigation of the entire brain without restriction of predefined regions-of-interest. Recent studies using this technique reported controversial results in patients with narcolepsy. PATIENTS AND METHODS: In this study, 12 patients with narcolepsy according to the criteria of the International Classification of Sleep Disorders were compared to 12 age-matched controls with normal MR images using VBM. Sex and global differences in voxel intensities were used as confounding covariates. RESULTS: Significant gray matter loss was found in the right prefrontal and frontomesial cortex of patients with narcolepsy. White matter comparison revealed no significant changes in patients or controls. The comparison of cerebrospinal fluid partition detected an enlargement of subarachnoidal space of controls close to the prefrontal cortex. CONCLUSIONS: The volume reduction of gray matter in narcoleptic patients could indicate a disease-related atrophy pattern. However, the results of VBM studies in narcolepsy are contradictory. A possible systematic bias due to inhomogeneous patient groups, stimulant medication history or pre-statistical image processing must be considered. We suggest that studies with drug-naive patients and/or region-of-interest-based volumetric studies should be performed in areas defined by VBM.

Adult↗
PubMed2005

Voxel-wise analysis of [123I]beta-CIT SPECT differentiates the Parkinson variant of multiple system atrophy from idiopathic Parkinson's disease.

To investigate the cerebral dopamine transporter status in the early stages of the parkinson-variant of multiple system atrophy (MSA-P), 15 patients with MSA-P and a disease duration up to 3 years were studied with [123I]beta-CIT single photon emission computed tomography (SPECT). Data were compared with 13 age-matched healthy control subjects and 15 patients with idiopathic Parkinson's disease (IPD), matched for age and disease duration. Parametric SPECT images of the specific-to-nondisplaceable equilibrium partition coefficient (V3''), which is proportional to the receptor density (Bmax) have been generated. To objectively localize focal changes in dopaminergic function throughout the entire brain volume without having to make an a priori hypothesis as to their location, statistical parametric mapping (SPM) was applied to our [123I]beta-CIT SPECT study. Both MSA-P and IPD patients showed significant decreases in striatal [123I]beta-CIT SPECT uptake. However, in MSA-P patients an additional reduction in midbrain [123I]beta-CIT signal was localized with SPM compared with control subjects (MSA-P, V3'': 0.89 +/- 0.37 versus controls V3'': 1.81 +/- 0.38; P < 0.001) and patients with IPD (V3'': 1.84 +/- 0.26; P < 0.001). Stepwise linear discriminant analysis of mean [123I]beta-CIT uptake in the putamen, caudate and midbrain identified the caudate and midbrain as indices to classify correctly 95.2% of subjects as either normal, patients with MSA-P or IPD. Voxel-wise analysis of [123I]beta-CIT SPECT revealed more widespread decline of monoaminergic transporter availability in MSA-P compared with IPD, matching the underlying pathological features. We suggest that the quantification of midbrain DAT signal should be included in the routine clinical analysis of [123I]beta-CIT SPECT in patients with uncertain parkinsonism.

Aged↗
PubMed2005

Transcranial ultrasound shows nigral hypoechogenicity in restless legs syndrome.

In patients with Parkinson's disease, hyperechogenicity of the substantia nigra using transcranial ultrasound has been related to increased tissue concentrations of iron. Recently, deficient iron transport mechanisms in substantia nigra neurons have been described in postmortem tissue of patients with restless legs syndrome (RLS). This study was performed to study substantia nigra echogenicity in RLS patients compared with normal control subjects and Parkinson's disease patients. RLS patients had significantly reduced midbrain areas of hyperechogenicity compared with control subjects, and even more markedly reduced hyperechogenicity compared with Parkinson's disease patients. These findings lend further support to nigral iron deficiency as a pathogenetic factor in RLS.

Aged↗
PubMed2005

Evidence-based medical review update: pharmacological and surgical treatments of Parkinson's disease: 2001 to 2004.

The objective of this study is to update a previous evidence-based medicine (EBM) review on Parkinson's disease (PD) treatments, adding January 2001 to January 2004 information. The Movement Disorder Society (MDS) Task Force prepared an EBM review of PD treatments covering data up to January 2001. The authors reviewed Level I (randomized clinical trials) reports of pharmacological and surgical interventions for PD, published as full articles in English (January 2001-January 2004). Inclusion criteria and ranking followed the original program and adhered to EBM methodology. For Efficacy Conclusions, treatments were designated Efficacious, Likely Efficacious, Non-Efficacious, or Insufficient Data. Four clinical indications were considered for each intervention: prevention of disease progression; treatment of Parkinsonism, as monotherapy and as adjuncts to levodopa where indicated; prevention of motor complications; treatment of motor complications. Twenty-seven new studies qualified for efficacy review, and others covered new safety issues. Apomorphine, piribedil, unilateral pallidotomy, and subthalamic nucleus stimulation moved upward in efficacy ratings. Rasagiline, was newly rated as Efficacious monotherapy for control of Parkinsonism. New Level I data moved human fetal nigral transplants, as performed to date, from Insufficient Data to Non- efficacious for the treatment of Parkinsonism, motor fluctuations, and dyskinesias. Selegiline was reassigned as Non-efficacious for the prevention of dyskinesias. Other designations did not change. In a field as active in clinical trials as PD, frequent updating of therapy-based reviews is essential. We consider a 3-year period a reasonable time frame for published updates and are working to establish a Web-based mechanism to update the report in an ongoing manner.

Amantadine↗
PubMed2005

How to diagnose dementia with Lewy bodies: state of the art.

Dementia with Lewy bodies (DLB) is the second most common cause of neurodegenerative dementia in older people that has only been recognized in the past decade and that remains widely underdiagnosed. At postmortem examination, affected patients show numerous alpha-synuclein-positive Lewy bodies (LB) in many parts of the cerebral cortex, particularly neocortical and limbic areas in addition to the nigral LB degeneration characteristic of Parkinson's disease (PD). Clinical presentation, unlike PD, is with progressive cognitive decline with particular deficits of visuospatial ability as well as frontal executive function accompanied by usually only mildly to moderately severe parkinsonism, which is often akineto-rigid without the classical parkinsonian rest-tremor. Further accompanying features include spontaneous recurrent visual hallucinations and conspicuous fluctuations in alertness and cognitive performance. The two main differential diagnoses are Alzheimer's disease (AD) and Parkinson's disease dementia (PDD). To improve the differential diagnosis of DLB, consensus criteria have been developed that establish possible and probable levels of clinical diagnostic accuracy. Generally, their sensitivity is variable and low but their specificity is high. Current consensus is to restrict a diagnosis of DLB only to patients with parkinsonism who develop dementia within 12 months of the onset of motor symptoms. Using operationalized criteria, DLB can be diagnosed clinically with an accuracy similar to that achieved for AD or PD. Ancillary investigations, particularly neuroimaging, can aid in differential diagnosis. We review the present state of the best practice in the clinical diagnosis of DLB. Future modifications of diagnostic criteria would ideally include the full range of clinical presentations that can be associated with LB disease.

Accidental Falls↗
PubMed2005

In vitro models of multiple system atrophy.

alpha-Synuclein represents the major constituent of oligodendroglial cytoplasmic inclusions, the hallmark lesion of multiple system atrophy (MSA), a progressive disorder that is associated with selective degenerative cell loss in basal ganglia, cerebellum, brainstem, and spinal cord. The role of abnormal alpha-synuclein aggregation in oligodendroglial cells is still obscure, in particular, whether alpha-synuclein might impair oligodendroglial and, secondarily, neuronal integrity of those cells in the diseased brain. In an attempt to answer some of these questions, we have developed an "in vitro model of MSA" by expressing the wild-type or C-terminally truncated form of alpha-synuclein in glial cell cultures. With this simplified system, we have demonstrated that alpha-synuclein significantly affects the survival of glia and its vulnerability to environmental stress, which might represent a major step in the pathogenesis of MSA.

Basal Ganglia↗
PubMed2005

Therapeutic strategies in multiple system atrophy.

This review provides an update on therapeutic principles and their implications for practical management in multiple system atrophy (MSA), a sporadic neurodegenerative disorder characterized clinically by various combinations of dysautonomia, Parkinsonism, or cerebellar ataxia, often associated with other warning features (red flags), and pathologically by cell loss, gliosis, and glial cytoplasmic inclusions in selected multiple regions of the brain and spinal cord. Because of the small number of randomized controlled trials, the management of MSA is largely based on empirical or open-label evidence. Parkinsonism often shows a poor or unsustained response to chronic levodopa therapy, although more patients than previously recognized may experience an initial moderate-to-good dopaminergic response. There is no effective drug treatment for cerebellar ataxia. However, features of dysautonomia such as orthostatic hypotension, urinary retention or incontinence, constipation, and impotence, may often be relieved if recognized by the treating physician. Because no drug treatment consistently benefits patients with this disease in the long-term, palliative therapies are all the more important. Novel symptomatic and neuroprotective therapies are urgently required.

Adrenergic alpha-Antagonists↗
PubMed2005

Treatment of dementia with Lewy bodies and Parkinson's disease dementia.

Cognitive decline and dementia affect approximately 30% to 40% of patients with idiopathic Parkinson's disease during the course of their illness. PD-dementia (PDD) and dementia with Lewy bodies (DLB) are second to Alzheimer's disease in causing degenerative dementia in the elderly. The nosological distinction of the conditions has remained controversial because of broad clinical and pathological overlap. Treatment issues in both clinical settings are virtually identical. Treatment of Parkinsonism is often complicated by drug-induced psychosis and reduced levodopa responsiveness. Cognition, alertness, attention, as well as apathy or aggressive behavior have been shown to respond to treatment with cholinesterase inhibitors in randomized controlled trials both in DLB and PDD. Such treatment may also improve hallucinosis, but many patients will require add-on treatment with atypical neuroleptics to control drug-induced psychotic reactions. Clozapine and quetiapine are the drugs most commonly used and, contrary to classic neuroleptics, risperidone or olanzapine do not seem to cause severe side effects according to published data.

Alzheimer Disease↗
PubMed2005

Homocysteine and serum markers of immune activation in primary dystonia.

The cause of primary dystonia remains unknown. Several reports point to immune system disturbances in primary dystonia and a recent study demonstrated hyperhomocysteinemia in cervical dystonia. Homocysteine (HCY) is an amino acid and elevated HCY concentrations were shown to be associated with immune system activation and increased neopterin serum concentrations. We examined HCY serum concentrations together with serum markers of immune activation in patients with different types of primary dystonia. Eighty-three patients with different types of primary dystonia were included and investigated at least 3 months following botulinum toxin treatment. Thirty-six healthy volunteers with similar age and sex distribution served as controls. Total serum HCY, kynurenine, and tryptophan concentrations were determined by high-performance liquid chromatography; neopterin, folate, and vitamin B12 concentrations were measured by immunoassays. Routine blood analysis, including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and white blood count (WBC), was performed. Patients with primary dystonia had significantly higher HCY concentrations compared to controls. Among the dystonia subtypes, no significant difference of HCY serum concentrations was observed. CRP and ESR were within the normal range in >90% of the patients and all had normal WBC. Neopterin, kynurenine, and tryptophan serum concentrations were similar in patients and controls and not correlated with HCY serum concentrations. The results provide evidence against enhanced cellular immune activation in patients with primary dystonia. However, hyperhomocysteinemia was present in all dystonia subtypes and unrelated to immune activation in this study. HCY is a neuronal excitotoxic amino acid and hyperhomocysteinemia is considered an independent vascular risk factor. Further studies are required to define the background of hyperhomocysteinemia in primary dystonia.

Adult↗
PubMed2005

Progression of parkinsonism in multiple system atrophy.

BACKGROUND: Progression of parkinsonian motor impairment is usually rapid and relentless in multiple system atrophy (MSA). However, it may also be subject to considerable variation. Prospective natural history studies using validated rating scales are required to accurately determine the progression of parkinsonism in MSA. OBJECTIVE: To assess the progression of parkinsonism in patients with the Parkinson variant of MSA. METHODS: Parkinsonian motor impairment was assessed on regular therapy at two time points (mean follow-up 11.8 months, SD 1.4) using the Hoehn and Yahr scale (H&Y), the Schwab and England ADL scale (SES) and the motor examination section of the UPDRS (UPDRS-III) in 38 patients with clinically probable MSA-P. RESULTS: We examined 38 patients with probable MSA-P (mean age 63.2 years, SD 7.4; mean disease duration 4.1 years, SD 3.0). The mean difference of UPDRS-III between baseline and follow-up was 10.8 (95% CI 8.6-12.9), consistent with an average annual 28.3 % increase of UPDRS-III baseline scores. Several variables were associated with faster progression of parkinsonism including low baseline global motor disability as assessed by H&Y and SES, low baseline UPDRS-III score, and short disease duration. UPDRS-III progression was unrelated to gender, age at symptom onset, and age at baseline visit. CONCLUSION: This is the first observational study on UPDRS rates of decline in MSA. The observed 28.6% annual increase of UPDRS-III scores illustrates the rapid progression of motor impairment in MSA. Furthermore, motor progression appeared to be accelerated during the early disease stages. Our data allow sample size calculations that may be helpful for the planning of future therapeutic trials.

Age of Onset↗
PubMed2005

Prevalence and incidence of Parkinson's disease in Europe.

OBJECTIVE: To provide an overview on the prevalence and incidence of Parkinson's disease (PD) in selected European countries. BACKGROUND: PD is a common disease of unknown etiology. Accurate information on the epidemiology of PD is critical to inform health policy. An aging population will lead to more patients with PD; thus, the high financial burden PD places on society will increase. MATERIAL AND METHODS: A systematic literature search was performed to identify studies on the prevalence and incidence of PD in the following European countries: Austria, the Czech Republic, France, Germany, Italy, The Netherlands, Portugal, Spain, Sweden and United Kingdom. Only published studies were included. Abstracts, reviews, meta-analyses and letters to the editor were excluded. There were no language restrictions. Data were extracted using a standardized assessment form, and evidence tables were used to systematically report and compare the data. RESULTS: Of 39 identified studies, most (87%) reported estimates of PD prevalence rates, while only a few (13%) reported estimates of PD annual incidence rates. Crude prevalence rate estimates ranged from 65.6 per 100,000 to 12,500 per 100,000 and annual incidence estimates ranged from 5 per 100,000 to 346 per 100,000. No publications could be identified for Austria or the Czech Republic. DISCUSSION AND CONCLUSION: The observed variations in prevalence and incidence rates may result from environmental or genetic factors, but might also be a consequence of differences in methodologies for case ascertainment, diagnostic criteria, or age distributions of the study populations. The comparability of existing studies is limited.

Age Distribution↗
PubMed2005

Animal models of multiple system atrophy.

Multiple system atrophy (MSA) is a fatal neurodegenerative disorder presenting with autonomic failure and motor impairment, primarily comprising L-dopa-resistant parkinsonism but occasionally involving cerebellar ataxia. These features result from progressive multisystem neuronal loss that is associated with oligodendroglial alpha-synuclein inclusions. The growing number of animal models for MSA reflects the search for a preclinical test-bed for elucidating MSA pathogenesis and for developing novel therapeutic interventions. Here, the currently available MSA animal models will be reviewed and leads for future research will be identified.

Animals↗
PubMed2005

Oxidative stress in transgenic mice with oligodendroglial alpha-synuclein overexpression replicates the characteristic neuropathology of multiple system atrophy.

Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterized by parkinsonism unresponsive to dopaminergic therapy, cerebellar ataxia, and dysautonomia. Neuropathology shows a characteristic neuronal multisystem degeneration that is associated with widespread oligodendroglial alpha-synuclein (alpha-SYN) inclusions. Presently no animal model completely replicates the specific neuropathology of MSA. Here we investigated the behavioral and pathological features resulting from oligodendroglial alpha-SYN overexpression in transgenic mice exposed to mitochondrial inhibition by 3-nitropropionic acid. In transgenic mice 3-nitropropionic acid induced or augmented motor deficits that were associated with MSA-like pathology including striatonigral degeneration and olivopontocerebellar atrophy. Widespread astrogliosis and microglial activation were also observed in the presence of alpha-SYN in oligodendrocytes. Our results indicate that combined mitochondrial inhibition and overexpression of oligodendroglial alpha-SYN generates a novel model of MSA that may be useful for evaluating both pathogenesis and treatment strategies.

Animals↗
PubMed2005

Prevalence of movement disorders in men and women aged 50-89 years (Bruneck Study cohort): a population-based study.

BACKGROUND: There is emerging awareness that movement disorders rank among the most common neurological diseases. However, the overall burden of these disorders in the general community is not well defined. We sought to assess the prevalence of all common categories of movement disorders in a population, accounting for sex differences and age trends. METHODS: As part of an ongoing prospective population-based study of carotid atherosclerosis and stroke risk (the Bruneck Study), a total of 706 men and women aged 50-89 years underwent a thorough neurological assessment. The diagnosis of movement disorders and ratings for disease severity were based on standard criteria and scales. Prevalences were estimated from logistic regression models (regression-smoothed rates) and standardised to the age and sex structure of the general community. FINDINGS: The prevalence of all common categories of movement disorders was 28.0% (95% CI 25.9-30.1). Proportions in men (27.6% [95% CI 24.5-30.7]) and women (28.3% [25.5-31.2]) were closely similar and sharply increased with age (from 18.5% [15.0-22.0] in 50-59-year olds to 51.3% [44.9-57.7] in 80-89-year olds). Almost half of all patients (90/214) had moderate-to-severe disease expression, but only 7.0% (15/214) received standard drug treatment. Prevalence of tremor was 14.5%, followed by restless legs syndrome (10.8%), parkinsonism (7%), primary dystonia and secondary dystonia (1.8%), and chorea and tics (<1% each). A fifth of all movement disorders were diagnosed to be probably drug-induced. INTERPRETATION: There is a high prevalence of and substantial under-recognition and under-treatment of movement disorders in the general community.

Age Factors↗
PubMed2005

Restless legs syndrome.

PURPOSE OF REVIEW: In the review period since February 2004 a number of papers have been published that make significant contributions to the current understanding of the epidemiology, clinical assessment, pathophysiology and treatment of restless legs syndrome. Those with the most significant findings were selected and will be reviewed. RECENT FINDINGS: Several epidemiological studies about restless legs syndrome have become available in the review period. A new susceptibility locus for restless legs syndrome has been reported. Neuropathological studies have provided profound insights into the key role of iron regulation in the pathophysiology of restless legs syndrome. Several randomized, double-blind, placebo-controlled studies have demonstrated that dopamine agonists are efficacious in the treatment of restless legs syndrome. A few pilot treatment studies with intravenous iron have been performed. SUMMARY: In this paper, recent advances in the field of restless legs syndrome are reviewed. Special emphasis is placed on pathophysiology and treatment. Restless legs syndrome is still an underdiagnosed disorder. The evidence basis for its treatment has been considerably increased in the review period.

Anticonvulsants↗