Parkinson Disease: Ransmayr 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.

Ransmayr G. · Abteilung für Neurologie und Psychiatrie, Allgemeines Krankenhaus der Stadt Linz. · Ther Umsch. · Pubmed #17221818 No free full text.

Abstract: The clinical criteria of Parkinson's disease are akinesia in combination with at least one of the following three symptoms: tremor (asymmetrical resting tremor), rigidity, impairment of posture, gait and balance. Symptomatic and atypical parkinsonian syndromes are ruled out by history, clinical examination, cranial CT, MRI, SPECT or PET. Patients with Parkinson's disease respond to levodopa or dopaminagonists throughout the course of the disease. Parkinson's disease is also characterised by various vegetative symptoms, impairment of olfaction, anxiety, depression, and with increasing age also by cognitive deficits and dementia.

Haubenberger D, Bonelli S, Hotzy C, Leitner P, Lichtner P, Samal D, Katzenschlager R, Djamshidian A, Brücke T, Steffelbauer M, Bancher C, Grossmann J, Ransmayr G, Strom TM, Meitinger T, Gasser T, Auff E, Zimprich A. · Department of Neurology, Medical University of Vienna, and SMZ-Ost Donauspital, Vienna, Austria. · Mov Disord. · Pubmed #17523199 No free full text.

Abstract: To investigate the frequency of mutations in the Leucine-Rich Repeat Kinase 2 gene (LRRK2) in a sample of Austrian Parkinson's disease (PD) patients, we sequenced the complete coding region in 16 patients with autosomal dominant PD. Furthermore, we sequenced exons 31, 35, and 41 additionally in 146 patients with idiopathic PD and 30 patients with dementia with Lewy bodies. Furthermore, all 192 patients were screened for 21 putative LRRK2 mutations. While the most common mutation G2019S and the risk variant G2385R were not found in our samples, we detected a novel missense mutation (S973N) in a patient with familial, late-onset and dopa-responsive PD.

Ransmayr G. · Department of Neurology and Psychiatry, General Hospital of the City of Linz, Linz, Austria. · Mov Disord. · Pubmed #17290463 No free full text.

Abstract: Constantin von Economo's (CvE) main scientific achievements were his studies on the cytoarchitectonics of the cerebral cortex, sleep, and encephalitis lethargica (EL). He found a close relationship between motor symptoms and psychiatric and behavioral disorders in EL and postencephalitic Parkinsonism and identified the underlying neuropathology in the diencephalon and the brainstem. In agreement with Tretiakoff's findings in Parkinson's disease, CvE related postencephalitic Parkinsonism to neuronal loss in the substantia nigra. Several of CvE's early, less well-known publications also deal with the basal ganglia and movement disorders. He demonstrated in rabbits that the substantia nigra modulates automatization, coordination, and succession of masticatory movements and swallowing. In a study on the effects of experimental lesions of the cerebral peduncle in cats and monkeys, CvE hypothesized a corticotegmental pathway that maintains motor functions after pyramidal tract lesions. Recent studies have identified this pathway, which ends in the pedunculopontine nucleus. In a study on posthemiplegic chorea, CvE discussed various pathophysiological hypotheses that partly resemble modern concepts of chorea. In a clinicopathological study on Wilson's disease, CvE traced the striofugal fibers and visualized the basal ganglia outflow pathways. CvE was an outstanding multidisciplinary movement disorder specialist who contributed substantially to modern basal ganglia research.

Ransmayr G. · Abteilung für Neurologie und Psychiatrie, Allgemeines Krankenhaus der Stadt Linz. · Praxis (Bern 1994). · Pubmed #16277084 No free full text.

Abstract: Dopamine agonists play an important role in the treatment of early Parkinson's disease, either as monotherapy or in combination with levodopa. Initial treatment with dopamine agonists has been found to postpone or prevent from motor fluctuations and dyskinesias. Dopamine agonists have also been shown to be significantly effective in the treatment of motor oscillations and dyskinesias related to chronic levodopa treatment. The "new" dopaminagonists pergolide, cabergoline, ropinirole and pramipexole tend to be more effective than bromocriptine. Due to side-effects dopamine agonists are mainly used in subjects younger than 70 to 75 years.

Hofer A, Berg D, Asmus F, Niwar M, Ransmayr G, Riemenschneider M, Bonelli SB, Steffelbauer M, Ceballos-Baumann A, Haussermann P, Behnke S, Krüger R, Prestel J, Sharma M, Zimprich A, Riess O, Gasser T. · Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, University of Tübingen, Germany. · J Neural Transm. · Pubmed #15622440 No free full text.

Abstract: BACKGROUND: A triplication of the alpha-synuclein gene was found to cause autosomal dominant Lewy body disease in two distinct families. METHOD: We searched for alterations of alpha-synuclein gene dosage and analysed the entire coding region for point mutations in 54 dementia with Lewy body disease (DLB) and in 103 young onset Parkinson's disease (PD) patients from Central Europe. RESULTS: We could not detect any quantitative alterations in the gene dosage of alpha-synuclein. Mutational screening of the entire coding region of alpha-synuclein revealed only one silent mutation V3V (adenine9guanine) in one case. CONCLUSIONS: Thus, this phenomenon appears not to be a major cause in the pathogenesis of sporadic DLB and young onset PD in this European population.

Bonelli SB, Ransmayr G, Steffelbauer M, Lukas T, Lampl C, Deibl M. · Department of Neurology and Psychiatry, Linz General Hospital, Linz, Austria. · Neurology. · Pubmed #15277644 No free full text.

Abstract: The authors analyzed whether nondemented (PD) and demented Parkinson patients (PDD) and patients with dementia with Lewy bodies (DLB) respond similarly in the levodopa test (LDT). Percentage of motor improvement was similar in the three groups; the proportion of patients with 10% and more improvement was greater in PD than in PDD and DLB. Positive LDT was predictive for favorable response in chronic levodopa treatment, but also some nonresponsive demented patients profited from chronic levodopa therapy.

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.

Ransmayr G. · Universitätsklinik für Neurologie, Anichstrasse 35, A-6020 Innsbruck. · Wien Med Wochenschr. · Pubmed #11925777 No free full text.

Abstract: Dementia with Lewy bodies (DLB) is the second most frequent neuropathologically diagnosed degenerative dementing illness. The clinical characteristics are progressive dementia, Parkinson syndrome, fluctuations of cognitive functions, vigilance and attention, visual hallucinations (usually detailed and well described), depression, REM-sleep behavior disorder, adverse responses to standard doses of neuroleptics, falls, syncopes, systematized delusions, and non-visual hallucinations. Mean age at disease onset ranges between 60 and 68 years. Male persons are more frequently affected than female. Disease duration is six to seven years. The differential diagnoses of DLB are dementia of the Alzheimer-type, Parkinson's disease, subcortical arteriosclerotic encephalopathy, progressive supranuclear palsy, multiple system atrophy, and, in rare cases, Creutzfeldt-Jakob disease. The genetic background of the disease is unclear. Magnetic resonance imaging and single photon emission tomography can contribute to the diagnosis. The disease is treated with L-dopa, atypical neuroleptics, acetylcholine esterase inhibitors, antihypotensive agents, and peripheral anticholinergic and alpha-receptor-blocking medicaments to improve neurogenic bladder dysfunction.

Boesch SM, Wenning GK, Ransmayr G, Poewe W. · Department of Neurology, University Hospital, Innsbruck, Austria. · J Neurol Neurosurg Psychiatry. · Pubmed #11861684 links to  free full text

Abstract: OBJECTIVE: To delineate the frequency and nature of dystonia in multiple system atrophy (MSA). METHODS: A cohort of 24 patients with clinically probable MSA over the past 10 years were prospectively followed up. Motor features were either dominated by parkinsonism (MSA-P subtype, n=18) or cerebellar ataxia (MSA-C, n=6). Classification of dystonic features and their changes with time was based on clinical observation during 6-12 monthly follow up visits. Parkinsonian features and complications of drug therapy were assessed. Most patients (22/24) died during the observation period. Neuropathological examination was confirmatory in all of the five necropsied patients. RESULTS: At first neurological visit dystonia was present in 11 (46%) patients all of whom had been levodopa naive at this time point. Six patients (25%) exhibited cervical dystonia (antecollis) (MSA-P n=4, MSA-C n=2), five patients (21%) showed unilateral limb dystonia (MSA-P n=4; MSA-C n=1). A definite initial response to levodopa treatment was seen in 15/18 patients with MSA-P, but in none of the six patients with MSA-C. A subgroup of 12 patients with MSA-P developed levodopa induced dyskinesias 2.3 years (range 0.5-4) after initiation of levodopa therapy. Most patients had peak dose craniocervical dystonia; however, some patients experienced limb or generalised dystonia. Isolated peak dose limb chorea occurred in only one patient. CONCLUSION: The prospective clinical study suggests that dystonia is common in untreated MSA-P. This finding may reflect younger age at disease onset and putaminal pathology in MSA-P. Levodopa induced dyskinesias were almost exclusively dystonic affecting predominantly craniocervical musculature. Future studies are required to elucidate the underlying pathophysiology of dystonia in MSA.

Ransmayr G, Seppi K, Donnemiller E, Luginger E, Marksteiner J, Riccabona G, Poewe W, Wenning GK. · Department of Neurology, University Hospital Innsbruck, Austria. · Eur J Nucl Med. · Pubmed #11685496 No free full text.

Abstract: The aim of this study was to compare parkinsonian features and loss of striatal dopamine transporter (DAT) function in patients with dementia with Lewy bodies (DLB) and Parkinson's disease (PD), matched for age and disease duration. Twenty patients with DLB. 24 PD patients and 10 matched controls were examined with SPET using a dual-head camera and the dopamine-transporter ligand 123I-beta-CIT (148 MBq). Moreover, in a subgroup of patients (16 DLB and 20 PD patients), subscores of the Unified Parkinson's Disease Rating Scale (UPDRS)-motor examination (ME) subscale were obtained during "practical off", i.e. 12 h following withdrawal of antiparkinsonian therapy. Compared with controls, striatal/cerebellar (S/C) ratios of DAT binding were significantly reduced in both DLB and PD, deficits being more marked in DLB patients (controls 7.2 +/- 1.2, DLB 3.3 +/- 1, PD 4.2 +/- 1.4; means +/- SD). The side-to-side differences in the S/C ratios were lower in the DLB group and the controls than in PD patients (0.4 +/- 0.4. 0.2 +/- 0.2 and 0.6 +/- 0.3, respectively, P<0.05). The total UPDRS-ME scores during practical-off were significantly higher in the DLB than in the PD group (41.2 +/- 12.7 vs 26.6 +/- 15.3, P<0.01). The side-to-side differences of the summed UPDRS extremity subscores were smaller in the DLB than in the PD group (2.2 +/- 2.3 vs 7.4 +/- 3.9, P<0.0001). Our findings suggest that parkinsonism evolves largely symmetrically and progresses more rapidly with more severe loss of striatal dopamine transporter function in DLB compared to PD. Whether these findings are helpful in the differential diagnosis of DLB and PD needs to be examined in further studies.

Kofler M, Müller J, Wenning GK, Reggiani L, Hollosi P, Bösch S, Ransmayr G, Valls-Solé J, Poewe W. · Department of Neurology, Hospital Hochzirl, Anna-Dengel-Haus, Austria. · Mov Disord. · Pubmed #11215594 No free full text.

Abstract: The auditory startle reaction to an unexpected loud stimulus is regarded as a brainstem reflex originating in the nucleus reticularis pontis caudalis and being distributed up the brainstem and down the spinal cord along slowly conducting pathways. Auditory startle responses (ASR) have been reported absent or reduced in progressive supranuclear palsy (PSP), and delayed in Parkinson's disease (PD), but normal in multiple-system atrophy (MSA). For the first time we studied ASR in patients fulfilling the clinical criteria of dementia with Lewy bodies (DLB) (n = 8), a neurodegenerative disorder characterized by cortical and subcortical depositions of Lewy bodies resulting in parkinsonism and progressive cognitive decline. For comparison, we also investigated patients with PD (n = 10), MSA (n = 7), PSP (n = 10), and age-matched healthy controls (n = 10). ASR were elicited by binaural high-intensity auditory stimuli. Surface electromyographic activity was simultaneously recorded from facial, upper, and lower extremity muscles. For each muscle, we assessed response probability and measured latency, amplitude, duration, and habituation rate. Patients with DLB had fewer and abnormally delayed ASR of low amplitude and short duration in extremity muscles compared to healthy controls. Furthermore, we confirm and extend previous findings of abnormal ASR in PSP and PD, and also demonstrate exaggerated ASR in extremity muscles of MSA patients. The different patterns of ASR abnormalities may reflect distinct types of brainstem dysfunction in DLB.

Durany N, Zöchling R, Boissl KW, Paulus W, Ransmayr G, Tatschner T, Danielczyk W, Jellinger K, Deckert J, Riederer P. · International University of Catalunya, Barcelona, Spain. · Neurosci Lett. · Pubmed #10854724 No free full text.

Abstract: The density of nicotinic alpha4beta2 receptors, which are believed to largely mediate nicotine's effects, has been reported to be decreased in post-mortem hippocampus of patients with schizophrenia. In the present study, using [(3)H]cytisine as a radioligand, we observed a significant 30% decrease in post-mortem striatum of patients with schizophrenia (n=12) as compared to controls (n=12). A 25% decrease of striatal alpha4beta2 receptor density in patients with Parkinson's syndrome (n=12) was not significant. As an upregulation of alpha4beta2 receptors has been observed due to nicotine consumption, the beneficial effects of nicotine described in patients with schizophrenia may be partly due to a compensation for a decrease in alpha4beta2 nicotinic acetylcholine receptors.

Kubis N, Faucheux BA, Ransmayr G, Damier P, Duyckaerts C, Henin D, Forette B, Le Charpentier Y, Hauw JJ, Agid Y, Hirsch EC. · INSERM U289 Hôpital de la Salpêtrière, Paris, France. · Brain. · Pubmed #10648443 links to  free full text

Abstract: Parkinson's disease is characterized by a progressive degeneration of dopaminergic neurons in the midbrain, yet the cause of this neuronal loss is still unknown. It has been hypothesized that Parkinson's disease could be the consequence of accelerated ageing. In order to reveal a possible common process during ageing and Parkinson's disease neurodegeneration, catecholaminergic neurons of five anatomical regions of the brainstem (substantia nigra, central grey substance, ventral tegmental area, peri- and retrorubral area, and locus coeruleus) have been quantified using immunohistochemical staining for tyrosine hydroxylase (TH) on regularly spaced sections, between the rostral and caudal poles of the mesencephalon and in the rostral pole of the pons, in post-mortem samples of 21 control subjects who died at ages 44-110 years. No statistically significant loss of TH positive neurons was observed in the older subjects, either in the substantia nigra or in the other midbrain regions that are known to degenerate to a lesser degree in Parkinson's disease. Furthermore, in the later regions no neuronal loss was observed from age 44 to 80 years, indicating that this result is not dependent on the inclusion of 'supernormal' very old people. These results suggest that from age 44 to 110 years, ageing in control adults is not, or is scarcely, accompanied by catecholaminergic cell loss in the midbrain and hence Parkinson's disease is probably not caused by an acceleration of a degenerative process during ageing.

Kronenberg MF, Menzel HJ, Ebersbach G, Wenning GK, Luginger E, Gollner M, Ransmayr G, Utermann G, Poewe W, Kronenberg F. · Department of Neurology, Innsbruck University Hospital, Austria. · Eur J Hum Genet. · Pubmed #10234518 links to  free full text

Abstract: Patients with idiopathic Parkinson's disease (IPD) are described as having markedly decreased novelty seeking characteristics. Since recent publications suggest an association between the dopamine D4 receptor polymorphism and novelty seeking, we investigated this polymorphism in a group of 122 patients with IPD and 127 healthy control subjects. We found similar allele and genotype frequencies in both groups and no association with the age of onset of symptoms. Therefore, the dopamine D4 receptor polymorphism does not confer genetic susceptibility to IPD and cannot explain the decreased novelty seeking in IPD patients.