Parkinson Disease: Jellinger K

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.

Sofic E, Sapcanin A, Tahirovic I, Gavrankapetanovic I, Jellinger K, Reynolds GP, Tatschner T, Riederer P. · Department of Chemistry, Faculty of Science, University of Sarajevo, Bosnia & Herzegovina. · J Neural Transm Suppl. · Pubmed #17447414 No free full text.

Abstract: Oxidative stress has been associated with damage and progressive cell death that occurs in neurodegenerative disorders such as Parkinson's disease (PD) and Alzheimer's disease (AD). The aim of this study was to investigate the antioxidant capacity in postmortem motor cortex (MC), nucleus caudatus (NC), gyrus temporalis (GT) and substantia nigra (SN) from controls (C) and patients with PD and AD. The initial samples consisted of 68 subjects of PD, AD and C. Brains were matched for age, sex and postmortem time. Brain tissue was homogenized in a phosphate buffer pH 7.3 and separated with two-step centrifugation at 15,000rpm for 30 min and 15,000 rpm for 10 min at 4 degrees C. Antioxidant capacity in the supernatants was measured using the oxygen radical absorbance assay (ORAC). The results showed that in the SN of parkinsonian's brain the balance between production of free radicals and the neutralization by a complex antioxidant system is disturbed. No changes in the antioxidant capacity of postmortem MC and NC of parkinsonian's brain in comparison with C were found. In the SN of parkinsonian's brain, antioxidant capacity seems to be lower in comparison with C (p < 0.05). Antioxidant capacity against peroxyl radical showed that MC of AD patients was lower than in the MC of C (p < 0.005). In NC of AD patients the antioxidant capacity against hydroxyl radical was increased in comparison with C (p < 0.04). No changes in the antioxidant capacity were found in brain tissues of AD in comparison with C, when CuSO4 was used as a free radical generator.

Müller J, Wenning GK, Verny M, McKee A, Chaudhuri KR, Jellinger K, Poewe W, Litvan I. · Cognitive Neuropharmacology Unit, The Champlain Building, 6410 Rockledge Dr, Suite 600, Bethesda, MD 20817-1844, USA. · Arch Neurol. · Pubmed #11176964 links to  free full text

Abstract: BACKGROUND: Dysarthria and dysphagia are known to occur in parkinsonian syndromes such as Parkinson disease (PD), dementia with Lewy bodies (DLB), corticobasal degeneration (CBD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). Differences in the evolution of these symptoms have not been studied systematically in postmortem-confirmed cases. OBJECTIVE: To study differences in the evolution of dysarthria and dysphagia in postmortem-confirmed parkinsonian disorders. PATIENTS AND METHODS: Eighty-three pathologically confirmed cases (PD, n = 17; MSA, n = 15; DLB, n = 14; PSP, n = 24; and CBD, n = 13) formed the basis for a multicenter clinicopathological study organized by the National Institute of Neurological Disorders and Stroke, Bethesda, Md. Cases with enough clinicopathological documentation for the purpose of the study were selected from research and neuropathological files of 7 medical centers in 4 countries (Austria, France, England, and the United States). RESULTS: Median dysarthria latencies were short in PSP and MSA (24 months each), intermediate in CBD and DLB (40 and 42 months), and long in PD (84 months). Median dysphagia latencies were intermediate in PSP (42 months), DLB (43 months), CBD (64 months), and MSA (67 months), and long in PD (130 months). Dysarthria or dysphagia within 1 year of disease onset was a distinguishing feature for atypical parkinsonian disorders (APDs) (specificity, 100%) but failed to further distinguish among the APDs. Survival time after onset of a complaint of dysphagia was similar in PD, MSA, and PSP (15 to 24 months, P =.7) and latency to a complaint of dysphagia was highly correlated with total survival time (rho = 0.88; P<.001) in all disorders. CONCLUSIONS: Latency to onset of dysarthria and dysphagia clearly differentiated PD from the APDs, but did not help distinguish different APDs. Survival after onset of dysphagia was similarly poor among all parkinsonian disorders. Evaluation and adequate treatment of patients with PD who complain of dysphagia might prevent or delay complications such as aspiration pneumonia, which in turn may improve quality of life and increase survival time.

Müller J, Wenning GK, Jellinger K, McKee A, Poewe W, Litvan I. · Cognitive Neuropharmacology Unit, Henry M. Jackson Foundation, Bethesda, MD 20817-1844, USA. · Neurology. · Pubmed #10994019 No free full text.

Abstract: The progression to different Hoehn and Yahr (HY) stages was evaluated in 81 pathologically confirmed patients with parkinsonism. Patients with PD (n = 18) showed significantly longer latencies to each HY stage than patients with atypical parkinsonian disorder (APD). While no patient with PD developed a HY-III stage within 1 year of onset of motor symptoms, 72% of those with APDs did. In fact, development of a HY-III within 1 year of motor onset accurately predicted an APD. However, the progression to each HY stage was unhelpful in distinguishing the APDs from each other. Once patients with PD and APD became wheelchair-bound, both had equally short survival times.

Haberler C, Alesch F, Mazal PR, Pilz P, Jellinger K, Pinter MM, Hainfellner JA, Budka H. · Institute of Neurology, University of Vienna, Austria. · Ann Neurol. · Pubmed #10976644 No free full text.

Abstract: We report on the pathological findings in the brains of 8 Parkinson's disease patients treated with deep brain stimulation (DBS) of the thalamic ventral intermediate nucleus (6 cases) and subthalamic nucleus (2 cases). DBS was performed continuously for up to 70 months. All brains showed well-preserved neural parenchyma and only mild gliosis around the lead track compatible with reactive changes due to surgical placement of the electrode. We conclude that chronic DBS does not cause damage to adjacent brain tissue.

Scherfler C, Puschban Z, Ghorayeb I, Goebel GP, Tison F, Jellinger K, Poewe W, Wenning GK. · Neurological Research Laboratory, University Hospital, Anichstrasse 35, 6020, Innsbruck, Austria. · Neuroscience. · Pubmed #10924951 No free full text.

Abstract: This study characterizes paw reaching, stepping and balance abnormalities in a double lesion rat model of striatonigral degeneration, the core pathology underlying levodopa unresponsive parkinsonism associated with multiple system atrophy. Extensive unilateral nigral or striatal lesions induced by 6-hydroxydopamine or quinolinic acid, respectively, produced a similarly marked contralateral paw reaching deficit without further deterioration following a secondary (complementary) lesion of ipsilateral striatum or substantia nigra. Contralateral stepping rates were reduced by unilateral 6-hydroxydopamine lesions without further deterioration following the secondary striatal lesion. In contrast, initial unilateral striatal quinolinic acid injections induced bilateral stepping deficits that significantly worsened contralaterally following the secondary nigral lesion. Contralateral sidefalling rates were significantly increased following primary nigral and striatal lesions. Secondary nigral but not secondary striatal lesions worsened contralateral sidefalling rates. Histological studies revealed subtotal (>90%) depletion of dopaminergic neurons in substantia nigra pars compacta and variable degrees of striatal degeneration depending on the lesion sequence. Animals pre-lesioned with 6-hydroxydopamine showed significantly larger residual striatal surface areas following the secondary striatal quinolinic acid lesion compared to animals with primary striatal quinolinic acid lesions (P<0.001). These findings are in line with previous experimental studies demonstrating that striatal dopamine depletion confers neuroprotection against subsequent excitotoxic injury. Whether loss of dopaminergic neurons protects against the striatal disease process occurring in multiple system atrophy (Parkinson-type) remains to be elucidated.In summary, this is the first experimental study to investigate spontaneous motor behaviour in a unilateral double lesion rat model. Our observations are consistent with a complex interaction of nigral and striatal lesions producing distinct behavioural and histological changes depending on the lesion sequence. Tests of forelimb akinesia and complex motor behaviour appear to provide a reliable tool that will be helpful for monitoring the effects of interventional strategies such as embryonic neuronal transplantation in the rat model of striatonigral degeneration.

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.

Wenning GK, Ebersbach G, Verny M, Chaudhuri KR, Jellinger K, McKee A, Poewe W, Litvan I. · Department of Neurology, University Hospital, Innsbruck, Austria. · Mov Disord. · Pubmed #10584668 No free full text.

Abstract: Although falls are known to occur in several parkinsonian disorders, such as Parkinson's disease (PD), multiple system atrophy (MSA), dementia with Lewy bodies (DLB), corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP), differences in the evolution of this feature have not been studied systematically in pathologically confirmed cases. Seventy-seven cases with pathologically confirmed parkinsonian disorders (PD: n = 11, MSA: n = 15, DLB: n = 14, CBD: n = 13, PSP: n = 24), collected up to 1994, formed the basis for a multicenter clinicopathologic study organized by the National Institute of Neurological Disorders and Stroke to improve differential diagnosis of parkinsonian disorders. In the present study, we determined the time course, that is, the duration from first symptom to onset (latency) and duration from onset to death, of recurrent falls. Furthermore, we analyzed the diagnostic validity of a predefined latency to onset of recurrent falls within 1 year of symptom onset. Significant group differences for latency, but not duration, of recurrent falls were observed. Latencies to onset of falls were short in PSP patients, intermediate in MSA, DLB, and CBD, and long in PD. Recurrent falls occurring within the first year after disease onset predicted PSP in 68% of the patients. Our study demonstrates for the first time that latency to onset, but not duration, of recurrent falls differentiates PD from other parkinsonian disorders. Whereas early falls are important for the diagnosis of PSP, the addition of other features increases its diagnostic predictive value.

Kienzl E, Jellinger K, Stachelberger H, Linert W. · Ludwig Boltzmann Institute of Clinical Neurobiology, PKH, Vienna, Austria. · Life Sci. · Pubmed #10576448 No free full text.

Abstract: The mechanisms leading to degeneration of melanized dopaminergic neurons in the brain stem, and particularly in the substantia nigra zona compacta (SNZC) in patients with Parkinson's disease (PD) are still unknown. Demonstration of increased iron Fe(III) in SNZC of PD brain has suggested that Fe-melanin interaction may contribute to oxidative neuronal damage. Energy dispersive X-ray electron microscopic analysis of the cellular distribution of trace elements revealed significant Fe-peaks, similar to those of a synthetic melanin-Fe(III) complex in intracytoplasmic electron-dense neuromelanin granules of SNZC neurons, with highest levels in a case of PD and Alzheimer's disease (AD). No Fe increase was found in Lewy bodies or in SN neurons of control specimens. The relevance of chemical reactions of dopamine (DA), 5-hydroxydopamine (5-OHDA), and 6-hydroxydopamine (6-OHDA) with Fe(III) and with dioxygen for the pathogenesis of PD was investigated. An initiating mechanism related to interaction between Fe and neuromelanin is suggested which results in accumulation of Fe(III) and a continuous production of cytotoxic species inducing a cascade of pathogenic reactions ultimately leading to neuronal death.

Zachhuber C, Leblhuber F, Bancher C, Jellinger K, Drlicek M. · Abteilung für Neurologisch-Psychiatrische Gerontologie, Landesnervenklinik Wagner-Jauregg, Linz. · Fortschr Neurol Psychiatr. · Pubmed #10093779 No free full text.

Abstract: Frontal lobe dementia (FLD) is characterised clinically by personality changes and a progressive speech disorder finally leading to mutism. In the course of the disease also other neurological syndromes may occur such as parkinsonism, a partial Klüver-Bucy-syndrome or a degeneration of motoneurons (FLD + MND). The latter leads to death within about three years. The clinical diagnosis of FLD is supported by functional (SPECT) and morphological (CT, MRI) investigations. From 1988 to 1997, 9 cases of FLD (6 female, 3 male) were clinically diagnosed at our department of Gerontology, LNK Linz. In two of these cases the clinical diagnosis was confirmed histopathologically. Characteristically, all except one patients showed a presenile beginning of the disease. The clinical course was slowly progressive with a mean duration of about 10 years. Special attention was given to additional signs and symptoms of motor neuron disease, parkinsonism and hyperorality. Six patients suffered from FLD + MND; parkinsonism (rigid-akinetic type) and a partial Klüver-Bucy-syndrome were diagnosed in 5 cases each. In histopathological investigations the incidence of FLD seems to increase. This type of dementia should be considered as an important diagnosis differential of presenile dementia-syndromes.

Jellinger K. · No affiliation provided · Eur J Neurol. · Pubmed #16987145 No free full text.

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Jellinger K. · No affiliation provided · Nervenarzt. · Pubmed #16639620 No free full text.

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Jellinger K. · No affiliation provided · Neurology. · Pubmed #12913222 No free full text.

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