Search PubMed⌕ Search

Biomedical subjects

Werner Poewe

Publications and source records attributed to Werner Poewe.

At least 91 records · Page 5Linked to original sources
PubMed2004

Trace of diffusion tensor differentiates the Parkinson variant of multiple system atrophy and Parkinson's disease.

We have recently shown that diffusion-weighted magnetic resonance (MR) imaging (DWI) discriminates patients with the Parkinson variant of multiple system atrophy (MSA-P) from those with Parkinson's disease (PD) by regional apparent diffusion coefficients (rADC) in the putamen. Because rADCs measured in one direction may underestimate diffusion-related pathologic processes, we investigated the diffusivity in different brain areas by trace of diffusion tensor (Trace(D)) in a new cohort of patients with MSA-P and PD. We studied 11 MSA-P, 17 PD patients, and 10 healthy volunteers matched for age and disease duration. Regional ADCs in three orthogonal directions and Trace(D) values were determined in selected brain regions including the basal ganglia, gray matter, white matter, substantia nigra, and pons. MSA-P patients had significantly higher putaminal and pallidal rTrace(D) values as well as rADCs in y- and z-direction than both PD patients and healthy volunteers. Moreover, putaminal Trace(D) discriminated completely MSA-P from both PD and healthy volunteers. The rADCs in the y- and z-direction provided a complete or near complete separation. In conclusion, our study confirms the results of previous studies of our group that patients with MSA-P show an increased putaminal diffusivity due to neuronal loss and gliosis. Because rADCs in one direction are dependent on the slice orientation relative to the directions of fiber tracts, Trace(D) imaging appears to be more accurate in the separation of MSA-P from PD.

Aged↗
PubMed2004

Number processing and basal ganglia dysfunction: a single case study.

Numerical processing has never been investigated in a case of Fahr's disease (FD) and only rarely in cases of basal ganglia dysfunction. The study describes the cognitive decline of a pre-morbidly high-functioning patient (medical doctor) affected by FD and his difficulties in number processing. A MRI scan revealed bilateral calcifications in the basal ganglia and a brain PET showed a massive reduction of glucose metabolism in the basal ganglia and both frontal lobes, but no other brain abnormalities. The patient's cognitive deficits included impairments in problem solving, in cognitive set shifting and in mental flexibility, as well as in verbal memory. These deficits are attributed to the disruption of the dorsolateral prefrontal circuit involving the basal ganglia. In number processing, the patient showed a severe deficit in the retrieval of multiplication facts, deficits in all tasks of numerical problem solving and in the execution of complex procedures. Importantly, he also showed a dense deficit in conceptual knowledge, which concerned all test conditions and all operations. The findings confirm the predictions of the triple code model in so far, as a disruption of cortico-subcortical loops involving the basal-ganglia may lead to specific deficits in fact retrieval. However, no verbal deficit, as assumed in the triple code model and reported in similar cases, could be observed. The present findings further add to current knowledge on numerical processing, showing how fronto-executive dysfunction may disrupt conceptual understanding of arithmetic. This study shows that not only parietal lesions may lead to severe deficits in conceptual understanding, but that basal ganglia lesions leading to frontal dysfunction may have a devastating effect.

Basal Ganglia Diseases↗
PubMed2004

Linguistic and neuropsychological deficits in crossed conduction aphasia. Report of three cases.

This study describes the linguistic and neuropsychological findings in three right-handed patients with crossed conduction aphasia. Despite the location of the lesion in the right hemisphere, all patients displayed a combination of linguistic deficits typically found in conduction aphasia following analogous damage to the left hemisphere. Associated cognitive deficits varied across the three patients. In addition, all cases showed deficits classically attributed to non-dominant hemisphere damage (visuoperceptual deficits and reduced figural memory). As a result, lesion-behaviour relationships in our study sample indicate both dominant and non-dominant qualities of the right hemisphere.

Adult↗
PubMed2004

Multiple system atrophy.

Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder characterised clinically by any combination of parkinsonian, autonomic, cerebellar, or pyramidal signs and pathologically by cell loss, gliosis, and glial cytoplasmic inclusions in several CNS structures. Owing to the recent advances in its molecular pathogenesis, MSA has been firmly established as an alpha-synucleinopathy along with other neurodegenerative diseases. In parallel, the clinical recognition of MSA has improved and the recent consensus diagnostic criteria have been widely established in the research community as well as movement disorders clinics. Although the diagnosis of this disorder is largely based on clinical expertise, several investigations have been proposed in the past decade to assist in early differential diagnosis. Symptomatic therapeutic strategies are still limited; however, several candidate neuroprotective agents have entered phase II and phase III clinical trials.

Animals↗
PubMed2004

Postural hand tremor before and following liver transplantation and immunosuppression with cyclosporine or tacrolimus in patients without clinical signs of hepatic encephalopathy.

OBJECTIVE: To assess tremor characteristics and severity in patients with severe liver disease without hepatic encephalopathy and following orthotopic liver transplantation (LTX) and immunosuppression (IS) with cyclosporin A (CsA) or tacrolimus (FK 506). METHODS: A total of 35 consecutive patients were included into the prospective study and serum levels of CsA (n = 29) or FK 506 (n = 6) were monitored following LTX. Tremor characteristics and severity were assessed by two-blinded raters before and following LTX. In addition, accelerometric recordings were taken before and after LTX, and compared with 16 normal controls without tremor and without clinical signs of hepatic encephalopathy or liver disease. Accelerometry was performed while sitting in a comfortable chair with the forearms supported and included rest and postural condition with and without weight load (500 g) on each hand. Kolmogorov-Smirnov test, paired t-test and t-test for independent samples were used for statistical analysis. RESULTS: The clinical rating revealed no rest but a mild postural hand tremor before LTX with a significant increase following LTX (p < 0.001). After LTX the mean score of postural tremor was significantly (p < 0.05) higher in patients with plasma levels of >850 ng CsA/ml compared with patients with lower levels. Patients and normal controls showed comparable mean peak frequencies of rest and postural hand tremor. The mean amplitude of postural hand tremor was significantly higher in patients before and after LTX compared with controls. In the majority of patients (89%) and controls (88%), the dominant tremor frequency decreased significantly (>1.5 Hz) when applying a weight load on each hand. CONCLUSION: The present study is the first to describe hand tremor characteristics in patients with severe liver disease without clinical signs of hepatic encephalopathy and in patients following LTX and IS. Compared with normal controls the patients showed a significant postural hand tremor prior and post-LTX and an increase of mean tremor amplitude following LTX and CsA/FK 506 treatment. The decrease of the dominant tremor frequency with weight load and an increase of tremor amplitude with higher plasma levels of CsA are both indicative of an enhanced physiological or toxic tremor.

Adult↗
PubMed2003

Atrophy pattern in SCA2 determined by voxel-based morphometry.

We applied voxel-based morphometry, an indirect volumetric technique, to MRI volumes of patients carrying the spinocerebellar ataxia type 2 mutation to determine patterns of brain atrophy. Nine patients were compared to 27 controls matched for age, sex and handedness. An optimised voxel-based morphometry protocol was used for pre-processing to minimize systematic bias. We observed significant volume loss in the cerebellar hemispheres, vermis, pons, mesencephalon and thalamus. Also affected were several supratentorial areas such as the right orbito-frontal cortex, right temporo-mesial cortex and the primary sensorimotor cortex bilaterally. The volumetric changes of cerebellar hemispheres were inversely correlated to cerebellar symptoms rated by a cerebellar ataxia scale. Two mechanisms could contribute to the observed cortical atrophy. It could be either the result of primary supratentorial degeneration as part of the disease process and/or secondary atrophy due to cerebellar deafferentation.

Ataxins↗
PubMed2003

Tumor necrosis factor-alpha-induced cell death in U373 cells overexpressing alpha-synuclein.

Intracellular alpha-synuclein inclusion formation in glial cells is frequently seen in Parkinson's disease and multiple system atrophy. Microglial activation in these neurodegenerative disorders suggests that neuroinflammatory responses might interact with alpha-synuclein and contribute to the pathogenesis of these disorders. To study the role of tumor necrosis factor-alpha (TNF-alpha), an important proinflammatory cytokine produced by microglia, on cells overexpressing alpha-synuclein we have used the astrocytoma cell line U373 engineered to express C-terminally truncated alpha-synuclein as a fusion protein with red or green fluorescent proteins. We demonstrate that alpha-synuclein overexpression augmented TNF-alpha-induced apoptotic cell death in U373 cells by induction of caspase activation. Furthermore, TNF-alpha exposure was associated with significant cytoskeletal changes characterized by altered inclusion composition with loss of cytoskeletal proteins and elevation of high-molecular-weight alpha-synuclein species. We conclude that alpha-synuclein overexpression significantly increases the vulnerability of U373 cells to apoptosis through TNF-alpha-mediated pathways.

Antineoplastic Agents↗
PubMed2003

Neuropathological and behavioral changes induced by various treatment paradigms with MPTP and 3-nitropropionic acid in mice: towards a model of striatonigral degeneration (multiple system atrophy).

We characterized two models of dual nigral and striatal lesions replicating the lesion pattern of striatonigral degeneration, the neuropathological hallmark of parkinsonism associated with multiple system atrophy (SND/MSA-P). For this purpose, we used systemic administration of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) and 3-nitropropionic acid (3-NP) in C57BL mice. One group of animals was first injected with MPTP followed by 3NP (MPTP+3-NP model). In the second group 3-NP was injected first, followed by MPTP (3-NP+MPTP model). The behavioral and neuropathological characteristics of these two models were compared to those observed after single 3-NP or MPTP intoxication. Results showed that, compared to control mice, spontaneous nocturnal locomotor activity was preserved in the MPTP+3-NP model, whereas it was reduced by 27% ( P<0.05) in the 3-NP+MPTP model and in animals treated with either 3-NP (27%, P<0.05) or MPTP (23%, P<0.05) alone. Quantitative histological evaluation based on Nissl staining and DARPP-32 immunohistochemistry revealed that 3-NP alone and 3-NP+MPTP treatment produced a marked (greater than 50%) loss of striatal neurons, whereas MPTP+3-NP treatment attenuated loss of striatal neurons by 43%. Further, loss of tyrosine hydroxylase-positive neurons in substantia nigra pars compacta (SNc) was attenuated after 3-NP+MPTP treatment compared to that observed after MPTP (40% vs 74%, P<0.001) and MPTP+3NP treatment (55% vs 74%, P<0.01). Our results show that MPTP-induced nigral lesions attenuate 3-NP toxicity and, reciprocally, that 3-NP-induced striatal lesions reduce MPTP toxicity. This suggests that complex integrative mechanisms are likely to regulate the vulnerability of the striatum and SNc to cell death in SND/MSA-P.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2003

Elastin polymorphism haplotype and intracranial aneurysms are not associated in Central Europe.

BACKGROUND AND PURPOSE: The occurrence of intracranial aneurysms and of aneurysmal subarachnoid hemorrhage are influenced by genetic factors. Recent genomic studies in Japan have defined 3 chromosomal loci and 1 haplotype of elastin polymorphisms as important risk factors, both for affected sib pairs and sporadic patients. METHODS: We have genotyped 2 single nucleotide polymorphisms in the elastin gene and evaluated their allelic association with intracranial aneurysm in a Central European sample of 30 familial and 175 sporadic patients and 235 population controls. RESULTS: We found no allelic association between this elastin polymorphism haplotype and intracranial aneurysm. CONCLUSIONS: Our data probably reflect increased genetic heterogeneity of intracranial aneurysm in Europe compared with Japan.

Adult↗
PubMed2003

Increased daytime sleepiness in Parkinson's disease: a questionnaire survey.

We evaluated the frequency and severity of excessive daytime sleepiness in an outpatient population with Parkinson's disease in comparison to age-matched controls and examined its relationship with antiparkinsonian drug therapy and sleep history. Increased daytime sleepiness and involuntary sleep episodes have been described in Parkinson's disease, but the etiology is not completely understood. The Epworth Sleepiness Scale (ESS), a validated questionnaire for daytime sleepiness, was prospectively administered to 99 consecutive outpatients with Parkinson's disease and 44 age-matched controls. In addition, a short sleep-screening questionnaire was used. The ESS revealed significantly increased daytime sleepiness in PD patients compared to controls (7.5 +/- 4.6 vs. 5.8 +/- 3.0, P = 0.013). The ESS score was abnormally high (10 or more) in 33 % of PD patients and 11.4% of controls (P = 0.001). ESS was not different between PD patients on levodopa monotherapy and those on levodopa and dopamine agonists, or between patients taking ergoline or non-ergoline dopamine agonists. In PD patients and in controls, sleepiness was significantly associated with reported heavy snoring. Increased daytime sleepiness is more frequent in patients with PD than in elderly controls. Similar to controls, increased daytime sleepiness in PD patients is correlated with heavy snoring.

Aged↗
PubMed2003

Voxel-based morphometry detects cortical atrophy in the Parkinson variant of multiple system atrophy.

To determine magnetic resonance imaging (MRI) patterns of brain atrophy in parkinsonian syndromes, we applied voxel-based morphometry (VBM) to segmented gray matter, white matter, and cerebrospinal fluid compartments of T(1)-weighted brain volumes of 12 patients with probable multiple system atrophy-parkinson variant (MSA-P) and 12 Parkinson's disease patients, comparing them with 12 normal controls matched for age. In comparison to controls, a cortical atrophy pattern was observed in MSA-P patients with significant clusters of volume loss in primary sensorimotor cortices bilateral, supplementary motor areas bilateral, right premotor cortex, prefrontal cortex bilateral (middle frontal gyri) and insular cortices bilateral; subcortical atrophy occurred bilaterally in caudate nuclei and putamen as well as in the midbrain. Furthermore, an enlargement of the cerebrospinal fluid compartment was found in the lateral ventricles, third ventricle, perimesencephalic and cerebellomedullar cavities. In PD patients, significant atrophy only occurred in left caudate head with enlargement of left lateral ventricle. Comparing MSA-P to PD patients, MSA-P showed a similar cortical pattern of atrophy as compared to controls. We conclude that VBM reveals selective cortical atrophy in patients with MSA-P affecting primary and higher order motor areas as well as prefrontal and insular cortices. Further studies are required to determine clinical and/or subclinical correlates of cortical atrophy in MSA-P.

Aged↗
PubMed2003

Psychosis in Parkinson's disease.

Psychosis is a disabling nonmotor complication of Parkinson's disease (PD). Visual hallucinations are the most common clinical manifestation and have been observed in up to 40% of patients with advanced disease in hospital-based series. Age, cognitive dysfunction, depression, as well as severity and duration of disease have all been identified as risk factors in multiple studies. All major antiparkinsonian drugs can induce psychosis in at-risk patients. Early drug-induced psychosis has been observed in up to 16% of patients treated with dopamine agonists and has been associated with increased risk for the development of dementia later on. Management of psychosis in PD is complex and includes control of potential triggers and reductions of polypharmacy as well as the addition of atypical antipsychotics. Cholinesterase inhibitors may prove an additional option in psychotic PD patients with dementia.

Antiparkinson Agents↗
PubMed2003

Role of dopamine transporter imaging in investigation of parkinsonian syndromes in routine clinical practice.

We discuss the potential role of dopamine transporter (DAT) imaging by single photon emission computed tomography (SPECT) as a biological marker for differentiating among parkinsonian disorders in routine clinical practice, and the implication for disease progression assessment is considered. Although clinical criteria enable accurate and reliable diagnosis of fully developed Parkinson's disease, there are several areas of diagnostic uncertainty relating to atypical parkinsonian disorders, isolated tremor symptoms not fulfilling essential tremor criteria, as well as drug-induced and psychogenetic parkinsonism. DAT-SPECT facilitates differential diagnosis of the different parkinsonian syndromes that cannot be reliably separated on clinical grounds and it can thus provide valuable diagnostic information in early disease.

Brain↗
PubMed2003

Auditory startle response in cervical dystonia.

The excitability of brainstem neurons is abnormally enhanced in patients with cervical dystonia (CD), but the extend of such abnormality is not known. We examined whether patients with CD showed abnormalities in the auditory startle response (ASR), a brainstem reflex elicited by an unexpected loud stimulus. Thirteen patients with CD were investigated 3 months after botulinum toxin treatment. Thirteen healthy volunteers served as controls. ASRs were elicited by binaural high-intensity auditory stimuli. Reflex electromyographic (EMG) activity was recorded simultaneously with surface electrodes bilaterally from masseter, orbicularis oculi, sternocleidomastoid, and biceps brachii muscles. We found that ASR onset latencies were similar for patients and controls. CD patients had significantly lower ASR probabilities than controls (P = 0.007). ASR area under the curve was significantly smaller in CD patients (P = 0.017). Similar to controls, patients showed a significant habituation of ASR (P < 0.001, each); however, CD patients showed a prolonged tonic or phasic EMG activity after the initial ASR that was not observed in controls. Normal latencies and recruitment pattern indicate a preserved organization of intrinsic neural pathways mediating ASR in CD. Reduced ASR probability and magnitude as well as prolonged EMG activity after the proper startle response corroborate and extend previous findings on brainstem dysfunction in CD.

Adult↗
PubMed2003

Medial temporal lobe activation during semantic language processing: fMRI findings in healthy left- and right-handers.

Medial temporal lobe (MTL) areas are well known to serve episodic memory functions; their contribution to semantic memory has been occasionally noticed but not studied in detail. In the present fMRI study, 35 right-handed and 35 left-handed healthy subjects performed a semantic decision paradigm during which subjects heard spoken concrete nouns designating objects and had to decide on whether these objects were available in the supermarket and cost lest then a certain amount of money. The control paradigm consisted of sequences of low and high tones where subjects had to decide whether a sequence contained two high tones. The resulting contrast activation of semantic decision versus tone decision involved neocortical temporal, parietal, and prefrontal areas. Additional significant, bilateral activations in the MTL, the hippocampal formation, and adjacent areas were found. The exact incidence and location of activation was studied in a single-subject analysis for all 70 subjects. At the chosen threshold of P<0.001, 94% of subjects showed activations in the MTL and inferior temporal lobe (ITL). Activations were found along the longitudinal axis of the MTL, including the hippocampal formation and the parahippocampal gyrus. In the ITL, parts of the fusiform and lingual gyri were activated. Activations were similar in right- and left-handers. We conclude from this study that the MTL and parts of the ITL can be added to the areas activated by semantic verbal memory processing.

Acoustic Stimulation↗
PubMed2002

Treatment interventions for Parkinson's disease: an evidence based assessment.

We did a systematic review, with a uniform method of assessment of efficacy and safety, to assess the different interventions available for the management of Parkinson's disease (drugs, surgical interventions, and physical treatments) with respect to the following indications: prevention of disease progression, symptomatic treatment of motor features (parkinsonism), symptomatic control of motor complications, prevention of motor complications, and symptomatic treatment of non-motor features. Our aim was not to define practice guidelines, but rather to improve clinicians' knowledge of the presently available published clinical evidence, based mainly on randomised controlled trials. We hope that our review will help doctors to incorporate this background into their own decision-making strategy to make appropriate choices with respect to the treatment of individual patients with Parkinson's disease.

Disease Progression↗