Biomedical subjects

Werner Poewe

Publications and source records attributed to Werner Poewe.

At least 37 records · Page 2Linked to original sources

PubMed2006

Facial recognition in primary focal dystonia.

The basal ganglia seem to be involved in emotional processing. Primary dystonia is a movement disorder considered to result from basal ganglia dysfunction, and the aim of the present study was to investigate emotion recognition in patients with primary focal dystonia. Thirty-two patients with primary cranial (n=12) and cervical (n=20) dystonia were compared to 32 healthy controls matched for age, sex, and educational level on the facially expressed emotion labeling (FEEL) test, a computer-based tool measuring a person's ability to recognize facially expressed emotions. Patients with cognitive impairment or depression were excluded. None of the patients received medication with a possible cognitive side effect profile and only those with mild to moderate dystonia were included. Patients with primary dystonia showed isolated deficits in the recognition of disgust (P=0.007), while no differences between patients and controls were found with regard to the other emotions (fear, happiness, surprise, sadness, and anger). The findings of the present study add further evidence to the conception that dystonia is not only a motor but a complex basal ganglia disorder including selective emotion recognition disturbances.

Adult↗

PubMed2006

Progression of multiple system atrophy (MSA): a prospective natural history study by the European MSA Study Group (EMSA SG).

The disease-specific Unified Multiple System Atrophy Rating Scale (UMSARS) has been developed recently and validated for assessing disease severity in multiple system atrophy (MSA). Here, we aimed at (1) assessing rates of disease progression in MSA and (2) validating UMSARS for sensitivity to change over time. Impairment was assessed at two time points 12 months apart using UMSARS Part I (historical review), UMSARS Part II (motor examination), as well as measures of global disease severity, including UMSARS Part IV, Hoehn and Yahr (HY) Parkinson's disease staging, Schwab England Activities of Daily Living (SE ADL), and a three-point global Severity Scale (SS3). Fifty patients (male:female ratio, 1:0.9; possible MSA, 16%; probable MSA, 84%; MSA-parkinsonian, 58%; MSA-cerebellar, 42%) were assessed twice with an interval of 12.3 months. UMSARS II scores progressed by 57.3% (P<0.0001) and UMSARS I scores by 35.6% (P<0.0001) in relation to the respective baseline scores with no differences between motor subtypes, diagnostic categories and gender. Significant inverse correlations between (1) UMSARS I or UMSARS II progression and (2) baseline disability measures (i.e., the respective UMSARS or SS3 scores) and disease duration were found. Furthermore, the increases in HY staging, SE ADL and SS3 correlated significantly with UMSARS I, UMSARS II, and UMSARS IV progression. This report is the first prospective study showing rapid annual UMSARS rates of decline in MSA. Our data contribute to the ongoing validation process of UMSARS, and they facilitate the planning and implementation of future neuroprotective intervention trials.

Adult↗

PubMed2006

Long-term benefits of rivastigmine in dementia associated with Parkinson's disease: an active treatment extension study.

In patients with dementia associated with Parkinson's disease (PD), the efficacy and safety of rivastigmine, an inhibitor of acetylcholinesterase and butyrylcholinesterase, were previously demonstrated in a 24-week double-blind placebo-controlled trial. Our objective was to determine whether benefits were sustained over the long term. Following the double-blind trial, all patients were permitted to enter an active treatment extension study, during which they received rivastigmine 3-12 mg/day. Standard safety assessments were performed. Efficacy assessments included the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog) and other measures of cognition, daily function, neuropsychiatric symptoms, and executive function. Of 433 patients who completed the double-blind trial, 334 entered and 273 completed the active treatment extension. At 48 weeks, the mean ADAS-cog score for the whole group improved by 2 points above baseline. Placebo patients switching to rivastigmine for the active treatment extension experienced a mean cognitive improvement similar to that of the original rivastigmine group during the double-blind trial. The adverse event profile was comparable to that seen in the double-blind trial. Long-term rivastigmine treatment appeared well tolerated and may provide sustained benefits in dementia associated with PD patients who remain on treatment for up to 48 weeks.

Activities of Daily Living↗

PubMed2006

Health-related quality of life in multiple system atrophy.

Although multiple system atrophy (MSA) is a neurodegenerative disorder leading to progressive disability and decreased life expectancy, little is known about patients' own evaluation of their illness and factors associated with poor health-related quality of life (Hr-QoL). We, therefore, assessed Hr-QoL and its determinants in MSA. The following scales were applied to 115 patients in the European MSA-Study Group (EMSA-SG) Natural History Study: Medical Outcome Study Short Form (SF-36), EQ-5D, Beck Depression Inventory (BDI), Mini-Mental state examination (MMSE), Unified MSA Rating Scale (UMSARS), Hoehn & Yahr (H&Y) Parkinson's disease staging scale, Composite Autonomic Symptom Scale (COMPASS), and Parkinson's Disease Sleep Scale (PDSS). Forty-six percent of patients had moderate to severe depression (BDI > or = 17); Hr-QoL scores on the SF-36 and EQ-5D were significantly impaired. Pain, the only domain with similar scores in MSA and published PD patients, was reported more frequently in patients with MSA-P (predominantly parkinsonian motor subtype) than MSA-C (predominantly cerebellar motor subtype; 76% vs. 50%; P = 0.005). Hr-QoL scores correlated most strongly with UMSARS motor, COMPASS, and BDI scores but not with MMSE scores, age at onset, or disease duration. The COMPASS and UMSARS activities of daily living scores were moderate-to-strong predictors for the SF-36 physical summary score and the BDI and UMSARS motor scores for the SF-36 mental summary score. This report is the first study to show that Hr-QoL is significantly impaired in MSA. Although not all possible factors related to impaired Hr-QoL in MSA could be assessed, autonomic dysfunction, motor impairment, and depression were most closely associated with poor Hr-QoL, and therapeutic management, therefore, should concentrate upon these aspects of the disease.

Anxiety↗

PubMed2006

Topography of putaminal degeneration in multiple system atrophy: a diffusion magnetic resonance study.

There is neuropathologic evidence that, in early stages of the Parkinson variant of multiple system atrophy (MSA-P), the putamen shows a distinct topographical pathology affecting predominantly the dorsolateral and caudal regions while leaving the rostral to midparts almost intact. We investigated the topographic profile of putaminal degeneration in MSA-P patients in vivo by means of diffusion-weighted imaging (DWI), which has been shown to reveal abnormalities in the basal ganglia of patients with MSA-P compared to patients with PD and healthy controls. For this purpose, regional trace of the diffusion tensor (rTrace(D)) values were determined in the entire, anterior, and posterior putamen in 15 patients with probable MSA-P, in 20 patients with PD, and in 11 healthy volunteers matched for age and disease duration. MSA-P patients had significantly higher rTrace(D) values in entire, anterior, and posterior putamen compared to both controls and PD patients. Trace(D) values were significantly higher in the posterior compared to the anterior putamen in the MSA-P group. There were no significant differences between posterior and anterior putamen in both the control and PD group. Our study demonstrates prominent involvement of the posterior putamen in early disease stages of MSA-P in vivo by assessing putaminal diffusivity with the help of DWI.

Humans↗

PubMed2006

Diffusion-weighted imaging in Huntington's disease.

Huntington's disease (HD) is an autosomal dominant progressive neurodegenerative disorder that results from an expanded trinucleotide (CAG) repeat on the huntingtin gene. Neurodegeneration in HD affects most prominently the basal ganglia. Therefore, diffusivity was obtained in the basal ganglia and thalamus of 29 patients with early HD and 27 healthy volunteers by means of the trace of the diffusion tensor (Trace(D)). Putaminal, caudate, pallidal, and thalamic Trace(D) values were increased in patients with HD compared with controls. Increased diffusivity in the putamen and caudate nucleus correlated with global functional impairment, CAG repeat length, as well as bicaudate ratio. Diffusion-weighted imaging appears to be a promising surrogate marker for disease severity in HD. Sensitivity to change remains to be established longitudinally.

Activities of Daily Living↗

PubMed2006

Valvular heart disease in Parkinson's disease vs. controls: An echocardiographic study.

Restrictive valvulopathy has been reported in association with dopamine agonist therapy in parkinsonian patients. The majority of reports have been related to pergolide, but anecdotal cases following treatment with bromocriptine or cabergoline have also been presented. It is presently unclear whether the potential induction of restrictive cardiac valvulopathy is a class effect of all dopamine agonists or if there is a differential risk between ergot and nonergot compounds. In this study, the frequency of a valvular regurgitation as assessed by routine transthoracic echocardiography was compared between 75 patients with Parkinson's disease (PD) treated with pergolide (n = 29), cabergoline (n = 13), pramipexole or ropinirole (n = 33), and 49 age-matched nonparkinsonian controls. The exposure to pergolide and cabergoline was associated with higher frequencies of valvular regurgitation grades 2 and 3 (31% and 47%) compared with age-matched controls (13%), while there was no increase of valvular regurgitation grades 2 and 3 in patients treated with nonergot compounds (10%). Evidence for restrictive valvulopathy was found in one patient treated with pergolide and cabergoline each. While this study shows similarly increased frequencies of valvular regurgitation in patients treated with the ergot agonists pergolide and cabergoline in comparison to both normal controls and patients treated with nonergot agonists, evidence for restrictive valvulopathy was only found in two cases. These results highlight the need for further prospective studies of the prevalence and underlying mechanisms of cardiac valvulopathy in PD patients treated with different dopamine agonists.

Aged↗

PubMed2006

Levodopa-induced sleepiness in the Parkinson variant of multiple system atrophy.

Recent observations suggest that levodopa can induce irresistible sleep onset in multiple system atrophy (MSA). Therefore, we assessed sleepiness during a levodopa challenge in 17 MSA compared with 23 Parkinson's disease (PD) patients using the Stanford Sleepiness Scale (SSS). SSS scores during the levodopa challenge compared with baseline were significantly increased in the MSA compared with the PD group. These findings suggest greater potential of levodopa to induce sleepiness in MSA compared with PD, which may be related to differences in basal ganglia and brainstem pathology between the two disorders.

Aged↗

PubMed2006

Minimal clinically important change on the unified Parkinson's disease rating scale.

The Unified Parkinson's Disease Rating Scale (UPDRS) is the main outcome measure in clinical trials of Parkinson's disease (PD). The minimal change that represents a clinically meaningful improvement is unknown. The objective of this study was to determine the minimal change on the UPDRS that represents a clinically meaningful improvement in early PD after 6 months of treatment. Data from two independent randomized treatment trials over 6 months involving 603 patients with de novo PD were analyzed to determine the minimal clinically important change (MCIC), referred to the status before treatment, for the UPDRS motor, activities of daily living (ADL), and total scores. An anchor-based method using ratings on a seven-point global clinical improvement was used. A change of five points on the UPDRS motor part was found to be the most appropriate cutoff score for all Hoehn and Yahr stages I to III, and a change of eight points for the UDPRS total score. For the UDPRS ADL score, an MCIC of two points for Hoehn and Yahr stages I/I.5 and II and of three points for Hoehn and Yahr stage II.5/III was the most appropriate cutoff score. These data give the first estimate for cutoffs defining clinically important changes in UPDRS ADL and motor scores. Further studies using larger databases from more diverse study populations are encouraged to better define and solidify the MCIC for the UPDRS.

Aged↗

PubMed2006

Deep brain stimulation: preoperative issues.

Numerous factors need to be taken into account in deciding whether a patient with Parkinson's disease (PD) is a candidate for deep brain stimulation. Patient-related personal factors including age and the presence of other comorbid disorders need to be considered. Neuropsychological and neuropsychiatric concerns relate both to the presurgical status of the patient and to the potential for surgery to result in new problems postoperatively. A number of factors related to the underlying PD need to be considered, including the specific parkinsonian motor indications (e.g., tremor, bradykinesia, gait dysfunction), previous medical therapies, including benefit from current therapy and adverse effects, and past surgical treatments. Definable causes of Parkinsonism, particularly atypical Parkinsonisms, should be considered. Finally, methods of evaluating outcomes should be defined and formalized. This is a report from the Consensus on Deep Brain Stimulation for Parkinson's Disease, a project commissioned by the Congress of Neurological Surgeons and the Movement Disorder Society (MDS). The report has been endorsed by the Scientific Issues Committee of the MDS and the American Society of Stereotactic and Functional Neurosurgery. It outlines answers to a series of questions developed to address all aspects of deep brain stimulation preoperative decision-making.

Brain↗

PubMed2006

Disturbance of rapid eye movement sleep in spinocerebellar ataxia type 2.

Five genetically confirmed spinocerebellar ataxia type 2 (SCA2) patients were admitted to our sleep laboratory for two all-night video-polysomnographies. A standard montage was used, including electroencephalography, vertical and horizontal electrooculography, electromyography of mental, submental, and tibialis anterior muscles, and respiratory monitoring. Four of five SCA2 patients had insufficient muscle atonia during rapid eye movement (REM) sleep. All patients exhibited myoclonic jerks during REM sleep, while elaborated behavior was not observed in the video. Abnormal motor control during sleep with periodic leg movements and REM sleep without atonia occurs frequently in SCA2. This finding may reflect a dysfunction of dopaminergic and/or brainstem and cerebellar outflow pathways.

Adult↗

PubMed2006

Social stigmatization in patients with cranial and cervical dystonia.

Patients with cranial and cervical dystonia (CCD) suffer from visible involuntary facial, head, and neck movements. Therefore, the social appearance of patients with CCD may be seriously affected and self-perceived stigma can be a major source of disability. The present study investigated enacted social stigmatization of patients with CCD. In a pilot study, a semantic differential scale for assessment of stigma was constructed and validated. The final scale contained eight items representing personality traits to be rated on a seven-point scale (-3 negative extreme to 3 positive extreme). Short video sequences (15 seconds) of patients with various types of CCD and age- and sex-matched healthy controls were presented to a sample of 80 biology students (mean age, 19.8 +/- 2.3 years). Immediately after presentation of each video sequence, the students were asked to perform stigma ratings. Significant differences between CCD patients and controls were found on all eight items (P < 0.001 for each). CCD patients were rated as less accountable for their actions, less likeable, less trustworthy, less attractive, less self-confident, more odd and different, more reserved, and more piteous than controls. CCD patients are subject to serious prejudice and enacted stigmatization. There is a need for informing the public about the nature and symptoms of this disorder and a need to support patients to cope with stigmatization.

Adult↗

PubMed2006

The natural history of Parkinson's disease.

Although Parkinson's disease (PD) is the only chronic neurodegenerative disorder for which there are effective symptomatic therapies no treatment has yet been identified that would significantly slow its natural progression. Studies into the natural history of Parkinson's disease have been complicated by issues of diagnostic accuracy, heterogeneity of different forms of the disease as well as confounding effects of age related comorbidities. Only recently results from placebo-controlled clinical trials have helped to define the rates of progression of motor dysfunction as assessed by the UPDRS in early PD. Studies in treated patients suggest that there may be different rates of progression in different phases of the disease with faster decline in earlier versus later stages. Measuring progression of motor symptoms, however, alone is insufficient to describe the natural history of PD and may also be inadequate to define clinically meaningful disease modification in intervention trials. Progression of global disability as captured in the Hoehn and Yahr scale is important to consider and progression to stage III with beginning postural impairment defines a major milestone in the natural history of this illness. In addition, non-motor symptoms have major impact on the natural history of PD. Dementia, sleep-wake cycle dysregulation and autonomic failure were present in 50-80% of patients in one recent 15 year-follow up study. Dementia and psychosis are also major risk factors for nursing home placement in PD. A prerequisite for effective interventions that would modify disease progression in Parkinson's disease is the identification of the earliest preclinical stages of illness. This is now become a realistic possibility with screening tests of olfactory function and subsequent functional imaging. Subjects at risk for Parkinson's disease should be the future focus of neuroprotective trials.

Clinical Trials as Topic↗

PubMed2006

The diagnosis of Parkinson's disease.

The correct diagnosis of Parkinson's disease is important for prognostic and therapeutic reasons and is essential for clinical research. Investigations of the diagnostic accuracy for the disease and other forms of parkinsonism in community-based samples of patients taking antiparkinsonian medication confirmed a diagnosis of parkinsonism in only 74% of patients and clinically probable Parkinson's disease in 53% of patients. Clinicopathological studies based on brain bank material from the UK and Canada have shown that clinicians diagnose the disease incorrectly in about 25% of patients. In these studies, the most common reasons for misdiagnosis were presence of essential tremor, vascular parkinsonism, and atypical parkinsonian syndromes. Infrequent diagnostic errors included Alzheimer's disease, dementia with Lewy bodies, and drug-induced parkinsonism. Increasing knowledge of the heterogeneous clinical presentation of the various parkinsonisms has resulted in improved diagnostic accuracy of the various parkinsonian syndromes in specialised movement-disorder units. Also genetic testing and various other ancillary tests, such as olfactory testing, MRI, and dopamine-transporter single-photon-emission computed-tomography imaging, help with clinical diagnostic decisions.

Diagnosis, Differential↗

PubMed2006

Seminar on choreas.

Chorea is one of the major types of involuntary movement disorders originating from dysfunctional neuronal networks interconnecting the basal ganglia and frontal cortical motor areas. The syndrome is characterised by a continuous flow of random, brief, involuntary muscle contractions and can result from a wide variety of causes. Diagnostic work-up can be straightforward in patients with a positive family history of Huntington's disease or acute-onset hemichorea in patients with lacunar stroke, but it can be a challenging and complex task in rare autoimmune or genetic choreas. Principles of management focus on establishing an aetiological classification and, if possible, removal of the cause. Preventive strategies may be possible in Huntington's disease where genetic counselling plays a major part. In this review we summarise the current understanding of the neuroanatomy and pathophysiology of chorea, its major aetiological classes, and principles of diagnostic work-up and management.

Basal Ganglia↗

PubMed2006

Daytime sleepiness and the COMT val158met polymorphism in patients with Parkinson disease.

STUDY OBJECTIVE: A preliminary study by our group suggested an association between daytime sleepiness and the catechol-O-methyltransferase (COMT) val158met polymorphism (rs4680) in patients with Parkinson disease (PD). We sought to confirm this association in a large group of patients with PD. DESIGN: Genetic association study in patients with PD. SETTING: Movement disorder sections at 2 university hospitals. PARTICIPANTS: PD patients with and without episodes of suddenly falling asleep matched for antiparkinsonian medication, disease duration, sex, and age, who participated in a previous genetic study on dopamine-receptor polymorphisms. INTERVENTIONS: Not applicable. MEASUREMENTS AND RESULTS: In this study, 240 patients with PD (154 men; age 65.1 +/- 6.1 years; disease duration 9.4 +/- 6.0 years) were included. Seventy had the met-met (LL), 116 the met-val (LH), and 54 the val-val (HH) genotype. In the combined LL+LH group (featuring reduced COMT activity), the mean Epworth Sleepiness Scale (ESS) score was 9.0 +/- 5.9 versus 11.0 +/- 6.1 in the HH (high COMT activity) group (P = .047). Forty-seven percent of the LL and LH patients had sudden sleep onset compared with 61% of the HH patients (P = .07). Logistic regression, however, showed that both pathologic ESS scores (i.e., > 10) and sudden sleep onset were predicted by subjective disease severity (P < .001 each) but not by the COMT genotype. CONCLUSIONS: Our previous finding that the L-allele may be associated with daytime sleepiness could not be confirmed in the present study. Altogether, our data do not support a clinically relevant effect of the COMT genotype on daytime sleepiness in PD.

Aged↗

PubMed2005

Allergic rhinitis, asthma, and atherosclerosis in the Bruneck and ARMY studies.

BACKGROUND: Several diseases characterized by chronic inflammation and immune activation have been linked to enhanced risk for atherosclerosis. The potential association between allergies and atherosclerosis, however, remains to be defined. METHODS: The association between common allergic diseases (allergic rhinitis and asthma) and 5-year development and progression of carotid atherosclerosis (Bruneck Study) and high intima-media thickness in carotid and femoral arteries (Atherosclerosis Risk Factors in Male Youngsters [ARMY] study) was investigated. The Bruneck Study is a prospective population-based survey of 826 men and women aged 40 to 70 years; the ARMY study is a cross-sectional evaluation of 141 men aged 17 or 18 years. RESULTS: Subjects with allergic disorders were at a significantly increased risk for high intima-media thickness in the ARMY study (odds ratio, 2.5; 95% confidence interval, 1.1-5.5; P=.03) and for atherosclerosis development and progression in the Bruneck Study (odds ratio, 3.8; 95% confidence interval, 1.4-10.2; P=.007). The associations remained significant after multivariate adjustment for a broad array of established and potential vascular risk factors. When IgE levels were substituted for the clinical allergy variable, findings were confirmed in the Bruneck Study (adjusted odds ratio, 1.7; 95% confidence interval, 1.1-8.0), for a 1-SD increase in IgE level (P=.02). CONCLUSIONS: This study documents enhanced atherosclerosis among subjects with common allergic diseases. Our findings fit well with the emerging concept that key components of allergies, such as leukotrienes or mast cells, are active in human atherogenesis and further extend the growing list of immune system-mediated and chronic inflammatory disorders that have been linked with enhanced risk for atherosclerosis.

Adolescent↗

PubMed2005

Voxel-wise analysis of diffusion weighted imaging reveals disruption of the olfactory tract in Parkinson's disease.

Diffusion weighted imaging (DWI) and the trace of diffusion tensor [Trace (D)], a marker of water molecule diffusivity, provide information on structural integrity of nervous tissues. To investigate structural lesions within the brain's neuronal architecture in early stages of Parkinson's disease, 12 patients with disease duration of 3.5 +/- 1.5 years were studied with DWI. Data were compared with 12 age-matched healthy control subjects. To objectively localize focal changes of structural neuronal integrity without having to make an a priori hypothesis as to its location statistical parametric mapping (SPM) was applied to our DWI study. SPM localized significant increases of diffusivity in the region of both olfactory tracts in patients (P < 0.001). Trace (D) cut-off values for the voxel cluster of the olfactory tracts have been calculated from the subjects entered into SPM and applied to a total of 17 different individuals (9 patients with Parkinson's disease, disease duration 3.1 +/- 1.3 years and 8 age-matched healthy subjects). Out of 17 subjects, 16 subjects, i.e. 94%, were correctly discriminated with a sensitivity of 100% and a specificity of 88%. All patients with Parkinson's disease were correctly classified and only one normal subject was classified as having the disease, underlining the high potential of this method to separate patients with the illness from healthy subjects. Increased diffusivity in the olfactory tract is in line with the well-established clinical finding of hyposmia in Parkinson's disease. Whether DWI can be used as a marker to identify individuals at risk to develop this disease remains to be shown.

Case-Control Studies↗