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Biomedical subjects

Werner Poewe

Publications and source records attributed to Werner Poewe.

At least 73 records · Page 4Linked to original sources
PubMed2005

Computerized tremor analysis of valproate-induced tremor: a comparative study of controlled-release versus conventional valproate.

PURPOSE: Valproate (VPA) induces postural tremor in 6-45% of patients. The characteristics of VPA-induced tremor have not yet been quantitatively assessed, and it is not known whether tremor prevalence or severity is affected by VPA formulation (controlled-release CR-VPA vs. conventional VPA). The aim of this study was quantitatively to assess tremor in epilepsy patients receiving VPA and to compare the effects of two VPA formulations (CR-VPA vs. VPA) on tremor severity. METHODS: In a prospective study, 18 consecutive patients with newly diagnosed focal or generalized epilepsy were assigned to receive alternately either VPA (n=10) or CR-VPA (n=8) monotherapy. Computerized tremor analysis was performed at baseline 1 day before initiating VPA treatment and repeated after a seizure-free period of >or=8 weeks, during which VPA doses had remained stable. Rest and postural tremor were recorded by accelerometry, and surface electromyograms (EMGs) were recorded from the wrist flexors and extensors. RESULTS: At baseline, the two groups had similar postural tremor amplitudes. At follow-up, the CR-VPA group had remained at the same level, whereas VPA subjects exhibited a significant increase in tremor amplitudes (p<0.05) despite comparable VPA doses and comparable plasma VPA concentrations at the time of tremor testing. CONCLUSIONS: This is the first study to assess quantitatively VPA-induced tremor by standardized tremor analysis. These results suggest that CR-VPA may cause less tremorigenic activity as compared with standard VPA. The mechanisms underlying this difference are unclear but may include greater peak-trough variation with VPA than with CR-VPA.

Activities of Daily Living↗
PubMed2004

Rivastigmine for dementia associated with Parkinson's disease.

BACKGROUND: Cholinergic deficits are prominent in patients who have dementia associated with Parkinson's disease. We investigated the effects of the dual cholinesterase inhibitor rivastigmine in such patients. METHODS: Patients in whom mild-to-moderate dementia developed at least 2 years after they received a clinical diagnosis of Parkinson's disease were randomly assigned to receive placebo or 3 to 12 mg of rivastigmine per day for 24 weeks. Primary efficacy variables were the scores for the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog) and Alzheimer's Disease Cooperative Study-Clinician's Global Impression of Change (ADCS-CGIC). Secondary clinical outcomes were the scores for the Alzheimer's Disease Cooperative Study-Activities of Daily Living, the 10-item Neuropsychiatric Inventory, the Mini-Mental State Examination, Cognitive Drug Research power of attention tests, the Verbal Fluency test, and the Ten Point Clock-Drawing test. RESULTS: A total of 541 patients were enrolled, and 410 completed the study. The outcomes were better among patients treated with rivastigmine than among those who received placebo; however, the differences between these two groups were moderate and similar to those reported in trials of rivastigmine for Alzheimer's disease. Rivastigmine-treated patients had a mean improvement of 2.1 points in the score for the 70-point ADAS-cog, from a baseline score of 23.8, as compared with a 0.7-point worsening in the placebo group, from a baseline score of 24.3 (P<0.001). Clinically meaningful improvements in the scores for the ADCS-CGIC were observed in 19.8 percent of patients in the rivastigmine group and 14.5 percent of those in the placebo group, and clinically meaningful worsening was observed in 13.0 percent and 23.1 percent, respectively (mean score at 24 weeks, 3.8 and 4.3, respectively; P=0.007). Significantly better outcomes were seen with rivastigmine with respect to all secondary efficacy variables. The most frequent adverse events were nausea (affecting 29.0 percent of patients in the rivastigmine group and 11.2 percent of those in the placebo group, P<0.001), vomiting (16.6 and 1.7 percent, P<0.001), and tremor (10.2 and 3.9 percent, P=0.01). CONCLUSIONS: In this placebo-controlled study, rivastigmine was associated with moderate improvements in dementia associated with Parkinson's disease but also with higher rates of nausea, vomiting, and tremor.

Aged↗
PubMed2004

Urinary albumin excretion is independently associated with carotid and femoral artery atherosclerosis in the general population.

AIMS: In diabetic patients, increased urinary albumin excretion (UAE), termed microalbuminuria when in the range between 30 and 300 mg/dL per day, is associated with a higher risk of atherosclerosis and its complications. Whether or not this notion applies to the general population is a matter of ongoing controversy because none of the few previous investigations among non-diabetics strictly represent the general community. METHODS AND RESULTS: Urinary albumin-to-creatinine ratio (uACR), a measure of UAE, was assessed from overnight spot urine samples in a population-based cohort of 684 individuals. The ratio was significantly related to age, gender, blood pressure, diabetes, markers of systemic inflammation, liver enzymes, and parathyroid hormone levels (P<0.001 each). Moreover, uACR emerged as a highly significant risk predictor of carotid and femoral artery atherosclerosis in the general community and the non-diabetic subpopulation alike (age/sex-adjusted P<0.001 each). In multivariable logistic regression analyses, odds ratios (95% CI) of carotid and femoral atherosclerosis amounted to 1.28 (1.01-1.61) and 1.44 (1.15-1.81) for a one unit increase in log(e)-transformed uACR (P=0.040 and 0.002). Corresponding odds ratios in non-diabetic subjects were 1.41 (1.09-1.84) and 1.54 (1.19-1.99) (P=0.010 and 0.001). Multivariable linear regression analyses yielded significant, or near significant, relations with carotid and femoral artery intima-media thickness and atherosclerosis scores (P=0.058-0.001). CONCLUSION: The uACR is significantly and independently associated with the presence and severity of atherosclerosis in the general population. The relation obtained was of a dose-response type and extended to levels far below what is termed microalbuminuria. The novel aspects of our study are its focus on various vascular territories and representivity of the general healthy population.

Aged↗
PubMed2004

Evaluation of [123I]IBZM pinhole SPECT for the detection of striatal dopamine D2 receptor availability in rats.

Single photon emission computed tomography (SPECT) and MRI coregistration have been assessed to characterize striatal dopamine D2/D3 receptor (D2/D3R) availability in rats following injection of the D2 and D3R radioligand [123I] iodobenzamide ([123I]IBZM). High-resolution SPECT data were obtained with a pinhole collimator. In order to precisely estimate brain regions of low radioligand uptake, SPECT images were coregistered onto a MRI template with high accuracy (maximum mismatch 1.1 mm). To evaluate an adequate dose of radioligand to be administered without exceeding the radioligand-to-receptor occupancy >5% and to define an appropriate time period for image acquisition, three untreated groups of animals received 29.6, 37, and 44.4 MBq of [123I]IBZM and underwent five consecutive SPECT acquisitions lasting 64 min each. Ratio calculations between specific striatal radioligand uptake and nondisplaceable cerebellar uptake revealed a secular equilibrium between 75 and 355 min post-tracer application in all three animal groups. Consequently, since the highest regional uptake values were obtained in the animal group receiving 44.4 MBq [123I]IBZM, this injection dose was considered to be appropriate. Finally, the capacity of the imaging method to detect distinct severity levels of striatal dopamine D2/D3 receptor loss was tested in a low, medium, and high dose quinolinic acid (QA) animal model of Huntington's disease. Motor impairment indicative of striatal dysfunction was monitored using amphetamine-induced rotational behavior and locomotor activity. Loss of striatal D2/D3R bearing medium-sized spiny neurons was assessed by DARPP-32 immunohistochemistry and compared to [123I]IBZM binding. Optical density measures of DARPP-32 immunohistochemistry demonstrated QA dose-dependent mild to subtotal unilateral striatal lesions ranging from 29.4% to 96.9% when compared to the nonlesioned side. Linear regression analysis showed that measurements of striatal DARPP-32 optical density and striatal [123I]IBZM uptake of the lesioned side were highly correlated (r2=0.83; P<0.001) whereas correlation with locomotor activity was less tight (r2=0.23; P<0.05; amphetamine-induced rotational behavior was not significantly correlated). This is the first study to demonstrate that in vivo [123I]IBZM SPECT and MRI coregistration are highly sensitive and, in contrast to behavioral measures, accurately detect mild to subtotal striatal lesions by measuring loss of D2/D3R availability. SPECT-MRI-based estimation of regional [123I]IBZM uptake provides a cost effective and widely available in vivo imaging technique for assessing striatal integrity in animal studies.

Animals↗
PubMed2004

Failure of caspase inhibition in the double-lesion rat model of striatonigral degeneration (multiple system atrophy).

In the present study we assessed the neuroprotective effects of the pan-caspase inhibitor z-VAD.fmk [N-benzyloxycarbony-valine-alanine-aspartate-(OMe)-fluoromethylketone], and the caspase-3 inhibitor Ac-DEVD.CHO (acetyl-aspartate-chloromethylketone) in the double-lesion rat model of striatonigral degeneration (SND), the core pathology underlying levodopa-unresponsive parkinsonism associated with multiple system atrophy (MSA). Male Wistar rats were divided into three groups, receiving either Ac-DEVD.CHO, z-VAD.fmk or normal saline before lesion surgery, comprising a sequential unilateral quinolinic acid (QA) lesion of the striatum followed by a 6-hydroxydopamine (6-OHDA) lesion of the ipsilateral medial forebrain bundle. At 2 weeks post lesion, all rats underwent testing of spontaneous nocturnal locomotor behavior in an automated Photobeam Activity System (FlexField). Immunohistochemistry was performed with tyrosine hydroxylase, dopamine and cyclic adenosine 3',5'-monophosphate-regulated phosphoprotein and glial fibrillary acidic protein antibodies. Morphometry was performed using computerized image analysis. Behavioral and morphological analysis failed to show striatal or nigral protection in caspase inhibitor-treated animals. Our findings suggest that anti-apoptotic strategies are unrewarding in the SND rat model and, therefore, alternative neuroprotective interventions such as anti-glutamatergic agents or inhibitors of microglial activation should be explored instead.

Amino Acid Chloromethyl Ketones↗
PubMed2004

Akathisia, restless legs and periodic limb movements in sleep in Parkinson's disease.

Restless legs syndrome (RLS) symptoms are often reported in Parkinson's disease (PD), but prevalence studies of RLS in PD are few and the results are inconsistent. In addition, clinical overlapping between RLS, "wearing-off"-related lower limb discomfort and restlessness, and akathisia complicate the clinical assessments of true RLS in PD. Underlying pathophysiology potentially shared by RLS and PD is mainly suggested by similarities in treatment response. Functional imaging studies in RLS are still inconclusive, although some authors have found subtle deficits in nigrostriatal terminal function. Long-term prospective studies of RLS cohorts will clarify whether or not RLS is associated with an increased risk for development of PD.

Akathisia, Drug-Induced↗
PubMed2004

Failure of neuronal protection by inhibition of glial activation in a rat model of striatonigral degeneration.

Previous studies in rodent models of neurodegenerative disorders have demonstrated that minocycline exerts neuroprotective effects unrelated to its antimicrobial action. The purpose of the present study was to analyze whether minocycline exhibits neuroprotective activity in a rat model of striatonigral degeneration (SND), the core pathology underlying levodopa-unresponsive parkinsonism associated with multiple system atrophy (MSA). We observed no significant effect of minocycline on locomotor impairment in double-lesioned SND rats. Minocycline significantly suppressed astroglial and microglial activation (P < 0.01); however, 3'5'-monophosphate-regulated phosphoprotein (DARPP 32) immunohistochemistry revealed no significant differences in striatal lesion volume of minocycline-treated versus untreated control SND rats. Furthermore, there was no protection of nigral dopaminergic neurons in the double-lesion model. We conclude that despite its astrocytic and microglial suppression, minocycline failed to attenuate lesion-induced neuronal damage in the SND rat model.

Animals↗
PubMed2004

Basal forebrain atrophy is a distinctive pattern in dementia with Lewy bodies.

We determined brain atrophy patterns in dementia with Lewy bodies and Alzheimer's disease using voxel-based morphometry, an indirect volumetry. Ten patients with dementia with Lewy bodies, 10 patients with Alzheimer's disease and 10 controls were included. All groups were matched for age; sex and global differences in voxel intensities were included as confounding covariates. We observed basal forebrain atrophy discriminating dementia with Lewy bodies from Alzheimer's disease. Compared to controls, atrophy of lateral prefrontal cortex and left premotor cortex was seen in dementia with Lewy bodies whereas atrophy of the medial temporal cortex, posterior parietal cortex, thalamus and temporo-occipital areas was observed in Alzheimer's disease. Atrophy of insular cortex was found in both patient groups.

Aged↗
PubMed2004

Association of daytime sleepiness with COMT polymorphism in patients with parkinson disease: a pilot study.

STUDY OBJECTIVES: To evaluate an association between catechol-O-methyltransferase (COMT) genotype and subjective daytime sleepiness in patients with Parkinson disease. DESIGN: Structured questionnaire study. SETTING: Tertiary Parkinson disease care center and sleep outpatients' department at the university hospital neurology department. PARTICIPANTS: All nondemented patients with idiopathic Parkinson disease who had been part of a previous study of D4-receptor polymorphisms in 1997 were eligible to participate. From the original sample of 113 patients, 46 participated in the study, 22 met exclusion criteria, and 43 were not available. INTERVENTIONS: Not applicable. MEASUREMENTS AND RESULTS: In this study, 46 patients were included (27 men, 19 women; 68.4 +/- 9.9 years of age; symptomatic disease duration, 12.2 +/- 5.2 years; Hoehn and Yahr stage in "on" of 2.6 +/- 0.8). Out of the 46 patients, 13 had LL genotype, 22 LH, and 11 HH. The Epworth Sleepiness Scale scores were 9.5 +/- 4.8 in LL, 8.5 +/- 4.7 in LH, and 6.8 +/- 3.1 in HH (mean +/- SD) (NS). LL and LH were grouped together. The Epworth Sleepiness Scale score was 11 or more in 40% of the LL+LH group, compared to 9.1% of the HH group (P = .039). The levodopa or dopamine-agonist doses and types did not differ between the LL+LH group versus the HH group. CONCLUSIONS: These preliminary data suggest an association of the Lallele and daytime sleepiness in patients with Parkinson disease.

Aged↗
PubMed2004

Osteoprotegerin is a risk factor for progressive atherosclerosis and cardiovascular disease.

BACKGROUND: Osteoprotegerin is a novel member of the tumor necrosis factor receptor superfamily and a soluble decoy receptor of the receptor activator of nuclear factor-kappaB ligand. Recent experimental research has implicated osteoprotegerin in atherogenesis, but epidemiological confirmation of this concept is sparse. METHODS AND RESULTS: As part of the prospective, population-based Bruneck Study, severity, initiation, and progression of atherosclerosis were assessed in carotid arteries. Cases of incident cardiovascular disease and vascular mortality were carefully recorded over a 10-year period (1990 to 2000). Osteoprotegerin levels were measured in samples obtained at baseline and during follow-up. Serum osteoprotegerin showed a strong association with numerous vascular risk factors, including age, diabetes, markers of systemic inflammation, chronic infection, and smoking. In multivariate analyses, osteoprotegerin was significantly related to severity and 10-year progression of carotid atherosclerosis. Furthermore, a high level of osteoprotegerin was an independent risk factor for incident cardiovascular disease (adjusted relative risk for the top versus bottom tertile group for osteoprotegerin 2.2 [1.3 to 3.8]; P=0.001) and vascular mortality (adjusted relative risk for the top versus bottom tertile group for osteoprotegerin 3.1 [1.2 to 8.2]; P=0.010) but not for mortality due to nonvascular causes. CONCLUSIONS: Osteoprotegerin is an independent risk factor for the progression of atherosclerosis and onset of cardiovascular disease.

Aged↗
PubMed2004

The role of COMT inhibition in the treatment of Parkinson's disease.

Several prospective double-blind, placebo-controlled trials have demonstrated that combining levodopa with the COMT inhibitor entacapone is efficacious in reducing motor fluctuations. Compared with levodopa alone, mean daily "on" time was increased by 1-1.7 hours, with a corresponding decrease in daily "off" time. In addition, some studies have shown that these benefits are associated with significant improvements in both UPDRS motor and ADL scores. These benefits have been shown to persist in long-term clinical trials with follow-up for up to 3 years. Recent studies have also examined the value of combining levodopa with entacapone in stable patients who do not experience motor response fluctuations. Here, too, benefits have been reported, especially in health-related quality of life measures. Studies to determine if administering levodopa in combination with entacapone will delay the development of dyskinesia and motor fluctuations are eagerly awaited.

Antiparkinson Agents↗
PubMed2004

Ninhydrin sweat test: a simple method for detecting antibodies neutralizing botulinum toxin type A.

Approximately 5% of patients with cervical dystonia receiving repeated botulinum neurotoxin A (BoNT/A) injections develop secondary loss of treatment benefit. Currently available tests to directly detect neutralizing BoNT/A antibodies (BoNT/A-AB) are either expensive or time consuming. To establish a simple, clinically useful test for antibody detection, we adapted the ninhydrin sweat test (NST). Eighteen dystonic patients with secondary nonresponse and clinically suspected BoNT/A-AB formation were tested for BoNT/A-AB in the mouse diaphragm test (MDT). In addition, the size of the anhidrotic area was determined by the NST 21 days after an intradermal dose of 10 U Dysport into the hypothenar region of the left palm. In nine patients, positive BoNT-AB titers were found in the MDT. There was a significant correlation between the BoNT/A-AB titers and the anhidrotic area (Spearman's rho = -0.9, P < 0.0001). Both tests provided comparably good results with respect to qualitative antibody detection. In the clinical situation of secondary nonresponse to BoNT/A therapy, the economical NST may be a helpful tool to detect neutralizing BoNT/A-AB.

Adult↗
PubMed2004

Abnormalities of dopaminergic neurotransmission in SCA2: a combined 123I-betaCIT and 123I-IBZM SPECT study.

Extrapyramidal features may occur in spinocerebellar ataxias consistent with neuropathological evidence of nigrostriatal involvement. Recently, striatal dopaminergic neurotransmission was found to be abnormal in the uncommon parkinsonian presentation of spinocerebellar ataxia type 2 (SCA2). We have investigated, therefore, striatal dopamine transporter and D2 receptor function in a series of 9 patients with the more common ataxic presentation of SCA2 using single photon emission computed tomography and beta-CIT as well as IBZM. Age-matched healthy subjects and patients with Parkinson's disease (PD) served as controls. All except 1 SCA2 patient exhibited slowness of limb movements without rigidity or rest tremor. In addition, cervical dystonia was present in 5 and dystonic head tremor in 2 SCA2 patients. Striatocerebellar (S/C) ratios of beta-CIT binding were significantly reduced in SCA2 patients compared to control subjects, and they were within the range of PD patients. S/C ratios of IBZM binding were significantly reduced in SCA2 patients compared to control subjects. We conclude that dopaminergic neurotransmission is impaired in the ataxic presentation of SCA2, with a prominent loss of striatal dopamine transporter function. Both slowness of limb movements as well as dystonia in the ataxic SCA2 phenotype may reflect dysfunction not only at cerebellar but also at basal ganglia level.

Adult↗
PubMed2004

Movement Disorder Society Task Force report on the Hoehn and Yahr staging scale: status and recommendations.

The Movement Disorder Society Task Force for Rating Scales for Parkinson's disease (PD) prepared a critique of the Hoehn and Yahr scale (HY). Strengths of the HY scale include its wide utilization and acceptance. Progressively higher stages correlate with neuroimaging studies of dopaminergic loss, and high correlations exist between the HY scale and some standardized scales of motor impairment, disability, and quality of life. Weaknesses include the scale's mixing of impairment and disability and its non-linearity. Because the HY scale is weighted heavily toward postural instability as the primary index of disease severity, it does not capture completely impairments or disability from other motor features of PD and gives no information on nonmotor problems. Direct clinimetric testing of the HY scale has been very limited, but the scale fulfills at least some criteria for reliability and validity, especially for the midranges of the scale (Stages 2-4). Although a "modified HY scale" that includes 0.5 increments has been adopted widely, no clinimetric data are available on this adaptation. The Task Force recommends that: (1) the HY scale be used in its original form for demographic presentation of patient groups; (2) when the HY scale is used for group description, medians and ranges should be reported and analysis of changes should use nonparametric methods; (3) in research settings, the HY scale is useful primarily for defining inclusion/exclusion criteria; (4) to retain simplicity, clinicians should "rate what you see" and therefore incorporate comorbidities when assigning a HY stage; and (5) because of the wide usage of the modified HY scale with 0.5 increments, this adaptation warrants clinimetric testing. Without such testing, however, the original five-point scales should be maintained.

Feasibility Studies↗
PubMed2004

Comparison of diffusion-weighted imaging and [123I]IBZM-SPECT for the differentiation of patients with the Parkinson variant of multiple system atrophy from those with Parkinson's disease.

Both dopamine D2 receptor (D2R) binding single-photon emission computed tomography (SPECT) with [123I]iodobenzamide (IBZM) and diffusion-weighted imaging (DWI) have been shown to contribute to the differential diagnosis of patients with the Parkinson variant of multiple system atrophy (MSA-P) and Parkinson's disease (PD). We aimed to compare these two routinely available functional imaging modalities in differentiating patients with MSA-P from PD. For this purpose, results obtained by DWI and IBZM-SPECT were intraindividually compared in a cross-sectional study of 15 MSA-P and 17 PD patients matched for age and disease duration. The activity ratios of striatal to frontal cortex uptake (S/FC ratio) were used as a semiquantitative measure of the relative density of basal ganglia dopamine receptors labeled by IBZM. Regional apparent diffusion coefficients (rADC) were determined in the striatum. MSA-P patients had significantly lower S/FC ratios and significantly higher striatal rADCs than both PD patients and healthy volunteers. There were no significant differences in S/FC ratios and striatal rADC between PD patients and healthy volunteers. Sensitivity of IBZM-SPECT versus DWI for the differentiation of MSA-P from PD was 80% versus 93%, specificity 71% versus 100%, the predictive accuracy 75% versus 97%, the positive predictive value 71% versus 100%, and the negative predictive value 80% versus 94%. Striatal rADCs had a significant higher overall predictive accuracy than D2R binding with IBZM. In summary, our data suggest that DWI may be more accurate compared to IBZM-SPECT in the differential diagnosis of MSA-P versus PD.

Basal Ganglia↗
PubMed2004

Levodopa in the treatment of Parkinson's disease: current controversies.

Levodopa is the most effective symptomatic agent in the treatment of Parkinson's disease (PD) and the "gold standard" against which new agents must be compared. However, there remain two areas of controversy: (1) whether levodopa is toxic, and (2) whether levodopa directly causes motor complications. Levodopa is toxic to cultured dopamine neurons, and this may be a problem in PD where there is evidence of oxidative stress in the nigra. However, there is little firm evidence to suggest that levodopa is toxic in vivo or in PD. Clinical trials have not clarified this situation. Levodopa is also associated with motor complications. Increasing evidence suggests that they are related, at least in part, to the short half-life of the drug (and its potential to induce pulsatile stimulation of dopamine receptors) rather than to specific properties of the molecule. Treatment strategies that provide more continuous stimulation of dopamine receptors provide reduced motor complications in MPTP monkeys and PD patients. These studies raise the possibility that more continuous and physiological delivery of levodopa might reduce the risk of motor complications. Clinical trials to test this hypothesis are underway. We review current evidence relating to these areas of controversy.

Antiparkinson Agents↗
PubMed2004

Development and validation of the Unified Multiple System Atrophy Rating Scale (UMSARS).

We aimed to develop and validate a novel rating scale for multiple system atrophy (Unified Multiple System Atrophy Rating Scale-UMSARS). The scale comprises the following components: Part I, historical, 12 items; Part II, motor examination, 14 items; Part III, autonomic examination; and Part IV, global disability scale. For validation purposes, 40 MSA patients were assessed in four centers by 4 raters per center (2 senior and 2 junior raters). The raters applied the UMSARS, as well as a range of other scales, including the Unified Parkinson's Disease Rating Scale (UPDRS) and the International Cooperative Ataxia Rating Scale (ICARS). Internal consistency was high for both UMSARS-I (Crohnbach's alpha = 0.84) and UMSARS-II (Crohnbach's alpha = 0.90) sections. The interrater reliability of most of the UMSARS-I and -II items as well as of total UMSARS-I and -II subscores was substantial (k(w) = 0.6-0.8) to excellent (k(w) > 0.8). UMSARS-II correlated well with UPDRS-III and ICARS (rs > 0.8). Depending on the degree of the patient's disability, completion of the entire UMSARS took 30 to 45 minutes. Based on our findings, the UMSARS appears to be a multidimensional, reliable, and valid scale for semiquantitative clinical assessments of MSA patients.

Activities of Daily Living↗