Parkinson Disease: Wenning G

Ransmayr G, Katzenschlager R, Dal-Bianco P, Wenning G, Bancher C, Jellinger K, Schmidt R, Poewe W. · Neurologische Universitätsklinik Graz, Medizinische Universität Graz. · Neuropsychiatr. · Pubmed #17640492 No free full text.

Abstract: Dementia with Lewy Bodies (DLB) accounts for approximately 20 % of all autopsy-confirmed dementias in the elderly. Presumably, DLB is underdiagnosed in patients without or with only mild Parkinsonian symptoms in the daily routine of memory clinics. This motivated the Austrian Alzheimer Society and the Austrian Parkinson Society to inform about core features, suggestive features and supportive clinical findings of DLB and to provide information on diagnostic possibilities leading to better differential diagnosis. We also guide in the management of DLB as pharmacological treatment can pose difficult dilemmas for the treating clinician.

Tolosa E, Wenning G, Poewe W. · Neurology Service, Hospital Clinic, University of Barcelona, Barcelona, Spain. · Lancet Neurol. · Pubmed #16361025 No free full text.

Abstract: 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.

Poewe W, Wenning G. · Department of Neurology, University Hospital, Innsbruck, Austria. · Eur J Neurol. · Pubmed #12464118 No free full text.

Abstract: The diagnosis of Parkinson's disease continues to be challenging with misdiagnosis rates as high as 20-30% in early stages. Such diagnostic inaccuracy is largely due to failure to recognize atypical parkinsonian disorders including multiple system atrophy (MSA), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and dementia with Lewy bodies (DLB). These disorders are characterized by distinctive sets of atypical features that have been incorporated into recent consensus diagnostic criteria. Early diagnosis of atypical parkinsonian disorders is important not only because of prognostic implications, but also because of variable therapeutic targets such as autonomic failure, apraxia or dementia.

Högl B, Saletu M, Brandauer E, Glatzl S, Frauscher B, Seppi K, Ulmer H, Wenning G, Poewe W. · Department of Neurology, University of Innsbruck, Austria. · Sleep. · Pubmed #12489899 No free full text.

Abstract: OBJECTIVES: To assess the therapeutic efficacy of modafinil in the treatment of increased daytime sleepiness in patients with Parkinson's disease (PD). DESIGN: Double-blind, randomized, placebo-controlled crossover study with two 2-week treatment blocks, separated by a 2-week washout phase. SETTING: Tertiary Parkinson's disease care center and sleep laboratory at university hospital neurology department. PATIENTS: Fifteen patients with idiopathic PD and daytime sleepiness (Epworth sleepiness score (ESS) 10 or more). INTERVENTIONS: Administration of placebo or modafinil as a single morning dose in a randomized crossover order. The modafinil dose was 100 mg in the first, and 200 mg in the second treatment week. MEASUREMENTS AND RESULTS: At baseline and at the end of each treatment block, sleepiness was evaluated using subjective (perceived sleepiness with the ESS) and objective measures (maintenance of wakefulness test). Twelve patients completed the study (9 male, 3 female; mean age 65.0 +/- 7.6 years, mean disease duration 6.8 +/- 4.1 years). Epworth scores were significantly improved with modafinil (3.42 +/- 3.90) compared to placebo (0.83 +/- 1.99; p = 0.011). Latency to sleep in the maintenance of wakefulness test was not significantly altered by modafinil treatment: 10.9 (3-40)/15.1 (2.5-40) minutes before/after placebo and 12 (2.6-40)/17.8 (4.2-40) minutes before/after modafinil (p = 0.139) [data given as mean +/- standard deviation or median (range)]. CONCLUSIONS: The results of this study suggest that modafinil improves daytime sleepiness in PD patients, at least on a subjective or behavioral level. Modafinil treatment may be considered for EDS in PD patients, in whom otherwise treatable causes of Excessive Daytime Sleepiness (EDS) are absent.

Ebersbach G, Stöck M, Müller J, Wenning G, Wissel J, Poewe W. · Department of Neurology, University Clinic Innsbruck, Austria. · Mov Disord. · Pubmed #10584678 No free full text.

Abstract: Nicotine has been reported to have positive effects on motor performance in patients with Parkinson's disease. In this study, motor performance was evaluated in 16 patients with idiopathic Parkinson's disease during a practical off-period using the motor part of the Unified Parkinson's Disease Rating Scale after 12 hours' exposure to a transdermal patch containing 35 mg nicotine or placebo. The study was performed using a double-blind crossover design. In contrast to previous reports, nicotine exposure was followed by a worsening of symptoms compared with placebo. A negative response to subthreshold dopaminergic stimulation, resulting from an inhibitory effect of low striatal dopamine concentrations acting on a subset of dopamine receptors, might possibly account for this finding.

Martinez-Rodriguez JE, Seppi K, Cardozo A, Iranzo A, Stampfer-Kountchev M, Wenning G, Tolosa E, Högl B, Santamaria J, Poewe W, Anonymous00335. · Neurology Service, Hospital Clínic de Barcelona and Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), University of Barcelona Medical School, Barcelona, Spain. · Mov Disord. · Pubmed #17659646 No free full text.

Abstract: Hypocretin (orexin) cerebrospinal fluid (CSF) levels have been previously found normal or decreased in Dementia with Lewy bodies and Parkinson disease, two synucleinopathies commonly associated with excessive daytime sleepiness (EDS). We evaluated CSF hypocretin-1 levels in 15 patients with moderately severe multiple system atrophy (MSA), another synucleinopathy where sleep disorders occur frequently and EDS has been reported, performing additional electrophysiological studies in 5 of them to assess the presence of EDS and sleep onset REM (SOREM) periods. Despite relatively low sleep efficiencies in nocturnal sleep, mean sleep latencies in the Multiple Sleep Latency Test were normal with no SOREM periods. All patients had CSF hypocretin-1 levels in the normal range (>200 pg/mL) suggesting that the hypocretin system is not altered in MSA, at least in patients with a moderately severe disease.

Peralta C, Werner P, Holl B, Kiechl S, Willeit J, Seppi K, Wenning G, Poewe W. · Department of Neurology, University of Innsbruck, Innsbruck, Austria. · J Neural Transm. · Pubmed #15340870 No free full text.

Abstract: A number of case reports have highlighted the occurrence of parkinsonism following strategic infarcts affecting the basal ganglia but the prevalence of parkinsonism after striatal infarcts (SI) has not been assessed. Therefore, we evaluated the clinical features and prevalence of parkinsonism in a large series of patients admitted to the Stroke-Unit of the Department of Neurology Innsbruck. Cerebral scans were retrospectively screened for SI, defined as a lesion larger than 1.5 cm involving the basal ganglia and the internal capsule. Out of 622 patients, 27 met the criteria for SI (4.3%) and 11 patients were available for follow-up. All patients presented contralateral motor weakness. Bilateral akinetic-rigid parkinsonism was found in only one patient whose [(123)I]beta-CIT-SPECT showed a decrease of the ligand uptake following the limits of the vascular lesion. Overall, parkinsonism does not appear to be a frequent consequence of striatal infarcts. Multiple lacunar subcortical infarcts interrupting thalamocortical drive may be more critical for the development of vascular parkinsonism.

Högl B, Seppi K, Brandauer E, Glatzl S, Frauscher B, Niedermüller U, Wenning G, Poewe W. · Department of Neurology, University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria. · Mov Disord. · Pubmed #12621636 No free full text.

Abstract: 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.

Scherfler C, Donnemiller E, Schocke M, Dierkes K, Decristoforo C, Oberladstätter M, Kolbitsch C, Zschiegner F, Riccabona G, Poewe W, Wenning G. · Department of Neurology, The Leopold-Franzens University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. · Neuroimage. · Pubmed #12482072 No free full text.

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

Ebersbach G, Sojer M, Müller J, Ransmayr G, Wenning G, Poewe W. · Fachkrankenhaus für Bewegungsstörungen/Parkinson, Paracelsusring 6a, 14547 Beelitz-Heilstätten. · Nervenarzt. · Pubmed #11975093 No free full text.

Abstract: Disturbance of balance in idiopathic Parkinson's disease (IPD) has a significant effect on disability. Yet the underlying mechanisms and the contribution of age-associated comorbidity to dysequilibrium are unclear. In this study, static posturography was performed in 30 healthy controls and 40 patients with IPD. Comparison of sway during quiet stance did not show significant differences between patients and controls. Multiple linear regression analysis was used to identify factors responsible for the considerable interindividual variance in patients. Results of the pull test, CT-verified cerebral microangiopathy, dementia, and age were assessed, but only cerebrovascular comorbidity contributed significantly to variance. Apart from increased sway, patients with coinciding cerebral microangiopathy (n = 20) more frequently had a history of falls or pathological responses in the pull test. The present results suggest that cerebrovascular comorbidity enhances dysequilibrium in IPD. Pathological sway in IPD can indicate comorbidity and may have implications for further diagnostics.