Parkinson Disease: Wenning GK

Goetz CG, Poewe W, Rascol O, Sampaio C, Stebbins GT, Counsell C, Giladi N, Holloway RG, Moore CG, Wenning GK, Yahr MD, Seidl L, Anonymous00253. · Rush University Medical Center, 1725 W. Harrison Street, Chicago, IL 60612, USA. · Mov Disord. · Pubmed #15372591 links to  free full text

Abstract: 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.

Geser F, Wenning GK, Poewe W, McKeith I. · Clinical Department of Neurology, Medical University Innsbruck, Austria. · Mov Disord. · Pubmed #16092075 No free full text.

Abstract: 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.

Seppi K, Schocke MF, Wenning GK, Poewe W. · Department of Neurology, Innsbruck Medical University, Austria. · J Neural Transm. · Pubmed #15997415 No free full text.

Abstract: The clinical differentiation between Parkinson's disease (PD) and multiple system atrophy (MSA) remains a challenge for each neurologist. The use of different magnetic resonance imaging (MRI) techniques including conventional MRI, proton magnetic resonance spectroscopy (MRS), diffusion-weighted imaging (DWI), magnetization transfer imaging (MTI) and MR volumetry (MRV) offer the potential for objective criteria in the differential diagnosis of neurodegenerative parkinsonism. The aim of this article is to review the role of different MRI techniques in the differential diagnosis of PD and MSA.

Stefanova N, Seppi K, Scherfler C, Puschban Z, Wenning GK. · Department of Neurology, University Hospital, Innsbruck, Austria. · J Neural Transm Suppl. · Pubmed #11205151 No free full text.

Abstract: Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA) are increasingly recognized as alpha-synucleinopathies, i.e. neurodegenerative disorders that share a common subcellular pathology characterized by alpha-synuclein abnormal aggregation. In the present review we focus on depression in alpha-synucleinopathies, discussing epidemiological, pathophysiological and treatment aspects of this frequently disabling clinical feature which may occur in PD, DLB and MSA alike.

Poewe W, Wenning GK. · Department of Neurology, University Hospital Innsbruck, Austria. · Mov Disord. · Pubmed #11009181 No free full text.

Abstract: Apomorphine was the first dopaminergic drug ever used to treat symptoms of Parkinson's disease. While powerful antiparkinsonian effects had been observed as early as 1951, the potential of treating fluctuating Parkinson's disease by subcutaneous administration of apomorphine has only recently become the subject of systematic study. A number of small scale clinical trials have unequivocally shown that intermittent subcutaneous apomorphine injections produce antiparkinsonian benefit close if not identical to that seen with levodopa and that apomorphine rescue injections can reliably revert off-periods even in patients with complex on-off motor swings. Continuous subcutaneous apomorphine infusions can reduce daily off-time by more than 50% in this group of patients, which appears to be a stronger effect than that generally seen with add-on therapy with oral dopamine agonists or COMT inhibitors. Extended follow-up studies of up to 8 years have demonstrated long-term persistence of apomorphine efficacy. In addition, there is convincing clinical evidence that monotherapy with continuous subcutaneous apomorphine infusions is associated with marked reductions of preexisting levodopa-induced dyskinesias. The main side effects of subcutaneous apomorphine treatment are related to cutaneous tolerability problems, whereas sedation and psychiatric complications play a lesser role. Given the marked degree of efficacy of subcutaneous apomorphine treatment in fluctuating Parkinson's disease, this approach seems to deserve more widespread clinical use.

Wenning GK, Bösch S, Luginger E, Wagner M, Poewe W. · Department of Neurology, University Hospital, Innsbruck, Austria. · Adv Neurol. · Pubmed #10410769 No free full text.

This publication has no abstract.

Wenning GK, Granata R, Puschban Z, Scherfler C, Poewe W. · Department of Neurology, University Hospital, Innsbruck, Austria. · J Neural Transm Suppl. · Pubmed #10335497 No free full text.

Abstract: Multiple system atrophy of the striatonigral degeneration (MSA-SND) type is increasingly recognized as major cause of neurodegenerative parkinsonism. Due to combined degeneration of substantia nigra pars compacta (SNC) and of striatum, antiparkinsonian therapy based on levodopa substitution eventually fails in more than 90% of patients. Animal models of MSA-SND are urgently required as test-bed for the evaluation of novel therapeutic interventions in this disorder such as neurotrophic factor delivery and neuronal transplantation. A number of well established rodent and primate models of Parkinson's (PD) and Huntington's (HD) disease replicate either nigral ("PD-like") or striatal ("HD-like") pathology and may therefore provide a useful baseline for the development of MSA-SND models. Previous attempts to mimick MSA-SND pathology in rodents have included sequential injections of 6-hydroxydopamine (6OHDA) and quinolinic acid (QA) into medial forebrain bundle and ipsilateral striatum, respectively ("double toxin-double lesion" approach). Preliminary evidence in rodents subjected to such lesions indicates that embryonic transplantation may partially reverse behavioural abnormalities. Intrastriatal injections of mitochondrial toxins such as 3-nitropropionic acid (3NP) and 1-methyl-4-phenylpyridinium (MPP+) in rodents result in (secondary) excitotoxic striatal lesions and subtotal neuronal degeneration of ipsilateral SNC, thus producing MSA-SND-like pathology by a simplified "single toxin-double lesion" approach. Comparative studies of human SND pathology and rodent striatonigral lesions are required in order to determine the rodent model(s) most closely mimicking the human disease process.

Gilman S, Low PA, Quinn N, Albanese A, Ben-Shlomo Y, Fowler CJ, Kaufmann H, Klockgether T, Lang AE, Lantos PL, Litvan I, Mathias CJ, Oliver E, Robertson D, Schatz I, Wenning GK. · Department of Neurology, University of Michigan Medical Center, Ann Arbor 48109-0316, USA. · J Neurol Sci. · Pubmed #10223419 No free full text.

Abstract: We report the results of a consensus conference on the diagnosis of multiple system atrophy (MSA). We describe the clinical features of the disease, which include four domains: autonomic failure/urinary dysfunction, parkinsonism and cerebellar ataxia, and corticospinal dysfunction. We set criteria to define the relative importance of these features. The diagnosis of possible MSA requires one criterion plus two features from separate other domains. The diagnosis of probable MSA requires the criterion for autonomic failure/urinary dysfunction plus poorly levodopa responsive parkinsonism or cerebellar ataxia. The diagnosis of definite MSA requires pathological confirmation.

Marras C, Lang AE, Ang LC, Zijlmans J, Wenning GK. · Toronto Western Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada. · Mov Disord. · Pubmed #11391758 No free full text.

This publication has no abstract.

Luginger E, Wenning GK, Bösch S, Poewe W. · Department of Neurology, University Hospital Innsbruck, Austria. · Mov Disord. · Pubmed #11009193 No free full text.

Abstract: L-Dopa-induced dyskinesias constitute a challenge to the management of advanced Parkinson's disease. According to recent reports, treatment with the NMDA receptor antagonist amantadine may significantly diminish L-dopa-induced dyskinesias. In the present study, the effect of amantadine on L-dopa-induced dykinesias was assessed in a 5-week, double-blind crossover trial. Dyskinesia severity as assessed following oral L-dopa challenges and by self-scoring dyskinesia diaries were reduced approximately 50% after amantadine treatment compared with baseline or placebo phases. Similarly, dyskinesia assessments on the Unified Parkinson's Disease Rating Scale, part IV (items 32 and 33) also revealed significant improvement after treatment with amantadine. The magnitude of the L-dopa motor response to oral challenges was not different after amantadine or placebo treatment, and there was no significant reduction of daily off-time when patients received active treatment. These results confirm previous observations concerning the antidyskinetic potential of amantadine.

Lipp A, Sandroni P, Ahlskog JE, Fealey RD, Kimpinski K, Iodice V, Gehrking TL, Weigand SD, Sletten DM, Gehrking JA, Nickander KK, Singer W, Maraganore DM, Gilman S, Wenning GK, Shults CW, Low PA. · Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA. · Arch Neurol. · Pubmed #19506134 No free full text.

Abstract: OBJECTIVE: To report preliminary results of a prospective ongoing study of multiple system atrophy (MSA) and Parkinson disease (PD), with a large subset of patients with PD with autonomic failure (25%), to evaluate autonomic indices that distinguish MSA from PD. METHODS: We used consensus criteria, detailed autonomic studies (Composite Autonomic Symptom Scale, Composite Autonomic Scoring Scale, thermoregulatory sweat test, and plasma catecholamines), and functional scales (Unified MSA Rating Scale [UMSARS] I-IV and Hoehn-Yahr grading) on a prospective, repeated, and ongoing basis. RESULTS: We report the results of a study on 52 patients with MSA (mean [SD], age, 61.1 [7.8] years; body mass index (calculated as weight in kilograms divided by height in meters squared), 27.2 [4.6]; Hoehn-Yahr grade, 3.2 [0.9]; UMSARS I score, 21.5 [7.4]; and UMSARS II score, 22.7 [9.0]) and 29 patients with PD, including PD with autonomic failure (mean [SD], age, 66.0 [8.1] years; body mass index, 26.6 [5.5]; Hoehn-Yahr grade, 2.2 [0.8]; UMSARS I score, 10.4 [6.1]; and UMSARS II score, 13.0 [5.9]). Autonomic indices were highly significantly more abnormal in MSA than PD (P < .001) for the Composite Autonomic Scoring Scale (5.9 [1.9] vs 3.3 [2.3], respectively), Composite Autonomic Symptom Scale (54.4 [21.8] vs 24.7 [20.5], respectively), and thermoregulatory sweat test (percentage anhidrosis, 57.4% [35.2%] vs 9.9% [17.7%], respectively). These differences were sustained and greater at 1-year follow-up, indicating a greater rate of progression of dysautonomia in MSA than PD. CONCLUSIONS: The severity, distribution, and pattern of autonomic deficits at study entry will distinguish MSA from PD, and MSA from PD with autonomic failure. These differences continue and are increased at follow-up. Our ongoing conclusion is that autonomic function tests can separate MSA from PD. Autonomic indices support the notion that the primary lesion in PD is ganglionic and postganglionic, while MSA is preganglionic.

Köllensperger M, Geser F, Seppi K, Stampfer-Kountchev M, Sawires M, Scherfler C, Boesch S, Mueller J, Koukouni V, Quinn N, Pellecchia MT, Barone P, Schimke N, Dodel R, Oertel W, Dupont E, Østergaard K, Daniels C, Deuschl G, Gurevich T, Giladi N, Coelho M, Sampaio C, Nilsson C, Widner H, Sorbo FD, Albanese A, Cardozo A, Tolosa E, Abele M, Klockgether T, Kamm C, Gasser T, Djaldetti R, Colosimo C, Meco G, Schrag A, Poewe W, Wenning GK, Anonymous00007. · Section for Clinical Neurobiology, Department of Neurology, Innsbruck Medical University, Austria. · Mov Disord. · Pubmed #18442131 No free full text.

Abstract: The clinical diagnosis of multiple system atrophy (MSA) is fraught with difficulty and there are no pathognomonic features to discriminate the parkinsonian variant (MSA-P) from Parkinson's disease (PD). Besides the poor response to levodopa, and the additional presence of pyramidal or cerebellar signs (ataxia) or autonomic failure as major diagnostic criteria, certain other clinical features known as "red flags" or warning signs may raise the clinical suspicion of MSA. To study the diagnostic role of these features in MSA-P versus PD patients, a standardized red flag check list (RFCL) developed by the European MSA Study Group (EMSA-SG) was administered to 57 patients with probable MSA-P and 116 patients with probable PD diagnosed according to established criteria. Those red flags with a specifity over 95% were selected for further analysis. Factor analysis was applied to reduce the number of red flags. The resulting set was then applied to 17 patients with possible MSA-P who on follow-up fulfilled criteria of probable MSA-P. Red flags were grouped into related categories. With two or more of six red flag categories present specificity was 98.3% and sensitivity was 84.2% in our cohort. When applying these criteria to patients with possible MSA-P, 76.5% of them would have been correctly diagnosed as probable MSA-P 15.9 (+/-7.0) months earlier than with the Consensus criteria alone. We propose a combination of two out of six red flag categories as additional diagnostic criteria for probable MSA-P.

Stefanova N, Poewe W, Wenning GK. · Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. · Exp Neurol. · Pubmed #18222424 No free full text.

Abstract: Rasagiline is a novel selective irreversible monoamine oxidase-B (MAO-B) inhibitor recently introduced for the symptomatic treatment of Parkinson disease. Like other propargylamines rasagiline has also shown neuroprotective effects independent of MAO-B-inhibition in various in vitro and in vivo models. The present study was performed to test the potential of rasagiline as a disease-modifying agent in multiple system atrophy (MSA) using a transgenic mouse model previously described by our group. (PLP)-alpha-synuclein transgenic mice featuring glial cytoplasmic inclusion pathology underwent 3-nitropropionic acid intoxication to model full-blown MSA-like neurodegeneration. Two doses of rasagiline were used (0.8 and 2.5 mg/kg) for a treatment period of 4 weeks. Rasagiline-treated animals were compared to placebo saline-treated mice by evaluation of motor behaviour and neuropathology. Motor behavioural tests including pole test, stride length test and general motor score evaluation showed improvements in motor deficits associated with 2.5 mg/kg rasagiline therapy. Immunohistochemistry and histology showed significant reduction of 3-NP-induced neuronal loss in striatum, substantia nigra pars compacta, cerebellar cortex, pontine nuclei and inferior olives of MSA mice receiving 2.5 mg/kg rasagiline. The results of the study indicate that rasagiline confers neuroprotection in a transgenic mouse model of MSA and may therefore be considered a promising disease-modifying candidate for human MSA.

Jellinger KA, Wenning GK, Seppi K. · Institute of Clinical Neurobiology, Vienna, Austria. · Neurodegener Dis. · Pubmed #17934326 No free full text.

Abstract: Retrospective analysis of 243 autopsy-confirmed cases of dementia with Lewy bodies (DLB) and Parkinson disease with dementia (PDD) showed an average age at symptom onset of 67 years and a median survival of 5 years from symptom onset. Older age at onset, fluctuating cognition, and hallucinations at onset predicted shorter survival; initial parkinsonism with delayed dementia significantly improved survival. Associated Alzheimer pathology also shortened survival. When adjusted for age, gender, and Alzheimer pathology, fluctuating dementia at symptom onset was identified as best predictor of poor outcome.

Köllensperger M, Seppi K, Liener C, Boesch S, Heute D, Mair KJ, Mueller J, Sawires M, Scherfler C, Schocke MF, Donnemilier E, Virgolini I, Wenning GK, Poewe W. · Clinical Department of Neurology, Innsbruck Medical University, Austria. · Mov Disord. · Pubmed #17579357 No free full text.

Abstract: Both diffusion weighted magnetic resonance imaging (DWI) of the basal ganglia and meta-iodobenzylguanidin (MIBG) scintigraphy of the heart have been reported useful in the differential diagnosis of patients with Parkinson's disease (PD) vs. the parkinson variant of multiple system atrophy (MSA-P). Their diagnostic value, however, has never been directly compared in patients with parkinsonism and autonomic dysfunction. We have studied 9 patients with PD and 9 patients with MSA-P matched for age and disease severity. Regional trace of the diffusion tensor values were determined in the putamina. Cardiac MIBG uptake was quantified by comparing regions of interest over heart and mediastinum Heart/Mediastinum (H/M) ratio. Furthermore, all patients underwent tilt testing. PD patients showed significantly lower H/M ratios than normal controls; however, there was considerable overlap between the two patient groups. We did not detect any significant differences of blood pressure response to passive tilt between the two patient groups. Sensitivity of MIBG scintigraphy versus DWI for the differentiation of MSA-P from PD was 55.6% vs. 100%, specificity 88.8% vs. 100%, and area under the curve 0.802 vs. 1.000. Our data suggest that DWI is superior to both tilt table testing and MIBG scintigraphy in the differential diagnosis of PD versus MSA-P.

Brenneis C, Egger K, Scherfler C, Seppi K, Schocke M, Poewe W, Wenning GK. · Clinical Department of Neurology, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria. · J Neurol. · Pubmed #17334661 No free full text.

Abstract: In this study, we aimed to determine the progression of brain atrophy in the parkinson variant of multiple system atrophy (MSA-P). Voxel-based morphometry was applied to two consecutive high resolution MR images of 14 patients with probable MSA-P in comparison to 14 patients with Parkinson's disease (PD). The time interval between baseline and follow-up investigations (1.0 +/- 0.5 SD years in MSAP and 1.4 +/- 0.6 SD years in PD patients) was introduced as covariate in the statistical analysis. Additionally, correlation analyses were performed between the progression maps and clinical data. We observed marked progression of brain atrophy in the MSA-P cohort, the regions including striatum, mesencephalon, thalamus and cerebellum, but also cortical regions such as the primary sensorimotor cortex, supplementary motor area, lateral premotor cortex, medial frontal gyrus, middle frontal gyrus, orbito-frontal cortex,insula, posterior parietal cortex and hippocampus. Short disease duration was correlated with progression of atrophy in the striatum whereas longer disease duration was correlated with increasing atrophy in the cortical areas and cerebellar hemispheres. The UPDRS-III score was not significantly correlated with any brain region. Our data suggest that cortical atrophy is prominent in MSA-P and early degeneration of the basal ganglia drives late onset cortical atrophy.

Stockner H, Sojer M, K KS, Mueller J, Wenning GK, Schmidauer C, Poewe W. · Department of Neurology, Medical University Innsbruck, Austria. · Mov Disord. · Pubmed #17226854 No free full text.

Abstract: Several studies have reported an increased risk to develop Parkinson's disease (PD) in essential tremor (ET) populations. Hyperechogenicity of the substantia nigra (SN) is a common transcranial sonography (TCS) finding in PD and has been suggested as a PD risk-marker in nonparkinsonian subjects. This study compared SN areas of 44 ET patients with 100 controls and 100 PD patients. Sixteen percent of ET patients had SN hyperechogenicity as compared with 3% of controls and 75% of PD patients. These findings might correspond to an increased risk of ET patients to develop PD. Long-term follow-up will show if those with hyperechogenic SN develop PD, while these without will not.

Peralta C, Stampfer-Kountchev M, Karner E, Köllensperger M, Geser F, Wolf E, Seppi K, Benke T, Poewe W, Wenning GK. · Clinical Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. · J Neural Transm. · Pubmed #17195917 No free full text.

Abstract: To compare frequency and degree of orthostatic hypotension (OH) in Parkinson's disease (PD) and Parkinson's disease with dementia (PDD) and its effect on attention and word fluency, blood pressure (BP) and heart rate changes during tilt were determined in 10 PD and 8 PDD patients. Attention and word fluency were evaluated in supine and tilted position using standard neuropsychological tests. OH defined as systolic BP (SBP) drop of >/=20 mmHg and/or diastolic BP (DBP) drop of >/=10 mmHg was present in 5 PDD patients and in 2 PD patients. SBP drop was significantly greater in PDD than in PD patients (P < 0.05). Whereas word fluency was unaffected by tilt in both patient groups, attention as assessed with the Test of Everyday Attention (TEA) deteriorated significantly in the PDD group, correlating with blood pressure response (DeltaSBP and TEA-2, r = 0.828, P < 0.05; DeltaDBP and TEA-2, r = 0.828, P < 0.05). We conclude that OH is frequent in PDD and should be addressed therapeutically since it may exacerbate attentional dysfunction.

Köllensperger M, Stefanova N, Reindl M, Poewe W, Wenning GK. · Clinical Department of Neurology, Innsbruck Medical University, Austria. · Mov Disord. · Pubmed #17149724 No free full text.

Abstract: The Parkinson variant of multiple system atrophy (MSA-P) is a distinct atypical parkinsonian disorder with a loss of dopaminergic neurons comparable to that found in Parkinson's disease (PD). The additional loss of striatopallidal projections is thought to account for levodopa unresponsiveness in MSA-P. Whereas histological features of MSA-P have been successfully reproduced in the double lesion rat model, loss of levodopa responsiveness has so far not been demonstrated. In the current study, 6-hydroxydopamine (6-OHDA) induced unilateral lesions of the substantia nigra produced a marked contralateral forelimb stepping deficit, which improved significantly after challenge with levodopa (P < 0.001). This response was abolished by the subsequent striatal quinolinic acid (QA) lesion. In the cylinder test, the marked asymmetry observed after 6-OHDA lesioning was reversed by levodopa to baseline levels. After QA, cylinder test performance under levodopa failed to reach baseline (P = 0.001) or 6-OHDA + levodopa (P = 0.002) levels. Nigral cell loss (90% +/- 5%) correlated with both stepping test (r = 0.608; P = 0.008) and cylinder test results (r = 0.656; P = 0.005). Lesion extent of the dorsal striatum correlated significantly with the loss of levodopa response (r = 0.593; P = 0.01) in the stepping test. These findings contribute further to the behavioral characterization of the double lesion rat model of MSA, improving its value in the evaluation of future neurorestorative strategies.

Löscher WN, Stampfer-Kountchev M, Sawires M, Seppi K, Mueller J, Szubski C, Hirnsperger K, Brenneis C, Poewe W, Wenning GK. · Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. · Mov Disord. · Pubmed #17133517 No free full text.

Abstract: We studied the response of the motor cortex to brief trains of suprathreshold repetitive transcranial magnetic stimulations (rTMS) in patients with the Parkinson-variant of multiple system atrophy (MSA-P) and compared it to patients with idiopathic Parkinson's disease (PD) and healthy controls. Eight subjects were studied in each group, and patients were matched for disease severity as assessed by Hoehn & Yahr stages. rTMS was delivered at rest and during low-level contractions in trains of 10 stimulations at 5 Hz, and stimulation intensity was set to result in an motor evoked potential (MEP) in the first dorsal interosseus muscle of 0.5 to 1.0 mV. In MSA-P, MEP amplitude at rest was already reduced after the second stimulus and remained so, while it did not change in PD and controls. During contraction, MEP size did not change during the train in any group. The silent period that followed the last stimulus was of similar duration as the first stimulus in MSA-P, but was increased in PD and controls. These findings indicate that abnormal inhibition occurs within the motor cortex in MSA-P, despite dopaminergic treatment and indicate differences in cortical dysfunction between MSA-P and PD. We suggest that these abnormalities reflect the motor cortex pathology found in MSA-P.

Hauser RA, Russ H, Haeger DA, Bruguiere-Fontenille M, Müller T, Wenning GK. · Parkinson's Disease and Movement Disorders Center, University of South Florida and Tampa General Healthcare, Tampa, FL 33606, USA. · Clin Neuropharmacol. · Pubmed #17095895 No free full text.

Abstract: OBJECTIVE: To evaluate patient perceptions of a new home diary designed to assess the duration and severity of dyskinesia in patients with Parkinson disease (PD) and to investigate whether the use of a training video and pictograms aids patient understanding of PD terminology. METHODS: Fifty advanced PD patients (Hoehn and Yahr stage 2.5-4.0; dyskinesia for >25% of the waking day) from the United States (n = 18), France (n = 12), and Germany (n = 20) were allocated alternately to 1 of 2 groups and shown a training video either with pictograms or without pictograms. The video explained the functional states "asleep," "OFF," "ON without dyskinesia," and "ON with dyskinesia," and how to complete the diary. Patients were given the corresponding version of the diary with or without pictograms to complete over a 24-hour period. Patients then participated in a second interview in which they were shown the alternate version of the video and diary for discussion only. RESULTS: Almost 95% of patients (47/50) reported that the video helped them to understand and clarify terms. Most patients [39/50 (78%)] preferred the diary with pictograms, but there was no evidence that pictograms improved the accuracy of diary completion. Overall, 80% of patients (40/50) completed the diaries correctly. Incorrect diary completion was usually because of confusion about the different functional states. CONCLUSIONS: Patients perceive diaries with pictograms as more helpful than those with words alone. Videos, in the patients' primary language, are considered valuable training aids that help patients complete daily diaries.

Seppi K, Peralta C, Diem-Zangerl A, Puschban Z, Mueller J, Poewe W, Wenning GK. · Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. · Eur J Neurol. · Pubmed #16987170 No free full text.

Abstract: We performed a placebo-controlled cross-over trial of riluzole (100 mg b.i.d.) in 10 patients with probable multiple system atrophy (MSA) administering riluzole and placebo for 4 weeks each with a 4-week washout period. Outcome measures evaluated short-term anti-Parkinsonian effects using the Unified Parkinson's Disease Rating Scale (UPDRS) subscales (UPDRS-II, activities of daily living; UPDRS-III, motor examination; sum of UPDRS-II and -III) before and at the end of each treatment phase. Delta values were calculated by subtracting the UPDRS scores measured at the end of each treatment arm from those before onset of each medication phase. Riluzole was generally well tolerated. There were no significant anti-Parkinsonian effects of riluzole comparing the UPDRS delta values for both treatment arms using the Wilcoxon signed-rank test. It is unlikely that riluzole treatment could have clinically meaningful anti-Parkinsonian effects in MSA. A trial assessing the disease-modifying potential of riluzole in MSA is underway.

Seppi K, Scherfler C, Donnemiller E, Virgolini I, Schocke MF, Goebel G, Mair KJ, Boesch S, Brenneis C, Wenning GK, Poewe W. · Department of Neurology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria. · Arch Neurol. · Pubmed #16908744 links to  free full text

Abstract: BACKGROUND: Dopaminergic loss can be visualized by means of iodine I 123-labeled 2beta-carbomethoxy-3beta-(4-iodophenyl)tropane ([(123)I]beta-CIT) single-photon emission computed tomography (SPECT) in several neurodegenerative parkinsonian disorders. Most previous SPECT studies have adopted region-of-interest methods for analysis, which are subjective and operator dependent. OBJECTIVE: To objectively localize the cerebral dopamine transporter status in the early stages of progressive supranuclear palsy (PSP). DESIGN: Prospective study. SETTING: Parkinson disease outpatient clinic. PATIENTS: Fourteen patients with PSP, 17 with Parkinson disease (PD), 15 with Parkinson-variant multiple-system atrophy (MSA-P), and 13 healthy control subjects, matched for age and disease duration. INTERVENTIONS: Statistical parametric mapping applied to [(123)I]beta-CIT SPECT. MAIN OUTCOME MEASURES: Differences in [(123)I]beta-CIT uptake. RESULTS: All patients with the different parkinsonian disorders showed a significant decrease in striatal [(123)I]beta-CIT uptake without any overlap with the control group. In patients with MSA-P and PSP, an additional reduction in brainstem [(123)I]beta-CIT signal compared with controls and patients with PD was identified with statistical parametric mapping. Midbrain [(123)I]beta-CIT uptake discriminated atypical parkinsonian disorders from PD with an overall correct classification of 91.3%. On the other hand, [(123)I]beta-CIT SPECT failed to discriminate PSP and MSA-P. CONCLUSION: By applying statistical parametric mapping to [(123)I]beta-CIT SPECT images of patients with PSP, a widespread decline of monoaminergic transporter availability including the striatum and brainstem was localized in PSP, discriminating patients with PSP from patients with PD, but not from those with MSA-P. Quantification of midbrain dopamine transporter signal may therefore enhance the utility of SPECT imaging in the differential diagnosis of patients with parkinsonism.

Seppi K, Högl B, Diem A, Peralta C, Wenning GK, Poewe W. · Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. · Mov Disord. · Pubmed #16639726 No free full text.

Abstract: 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.

Peralta C, Wolf E, Alber H, Seppi K, Müller S, Bösch S, Wenning GK, Pachinger O, Poewe W. · Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. · Mov Disord. · Pubmed #16622856 No free full text.

Abstract: 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.