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At least 19 recordsLinked to original sources
PubMed1999

[Psychotic symptoms as initial manifestation of a multiple system atrophy].

Multiple system atrophy is a disease characterised clinically by any combination of parkinsonian, pyramidal, autonomic or cerebellar symptoms and signs. This neurological status is often complicated by associated mental disturbances such as deficits in concentration, memory or learning. There are only very few reports in the literature describing cases of multiple system atrophy associated with psychotic symptoms. We report on two cases in which psychotic symptoms were the initial manifestation of multiple system atrophy. In view of the known neuropathologic and biochemical changes in multiple system atrophy the concurrent incidence of paranoid-hallucinatoric symptoms seems not uncommon and should be studied further.

Adult↗
PubMed2007

Brainstem respiratory control: substrates of respiratory failure of multiple system atrophy.

Multiple system atrophy may manifest with severe respiratory disorders, including sleep apnea and laryngeal stridor, which reflect a failure of automatic control of respiration. This function depends on a pontomedullary network of interconnected neurons located in the parabrachial/Kölliker Fuse nucleus in the pons, nucleus of the solitary tract, and ventrolateral medulla. Neurons in the preBötzinger complex expressing neurokinin-1 receptors are critically involved in respiratory rhythmogenesis, whereas serotonergic neurons in the medullary raphe and glutamatergic neurons located close to the ventral medullary surface are involved in central chemosensitivity to hypercapnia, hypoxia, or both. Pathological studies using selective neurochemical markers indicate that these neuronal groups are affected in multiple system atrophy. This finding may provide potential anatomical substrates for the respiratory manifestations of the disease.

Apnea↗
PubMed2000

Continuous positive air pressure eliminates nocturnal stridor in multiple system atrophy. Barcelona Multiple System Atrophy Study Group.

We prospectively studied the sleep patterns and laryngeal function of 20 patients with multiple system atrophy and found sleep disturbances in all subjects and vocal cord abduction dysfunction in 14 (70%). In three patients with nocturnal stridor and complete vocal cord abductor dysfunction, continuous positive airways pressure eliminated laryngeal stridor, obstructive apnoea, and haemoglobin desaturation.

Female↗
PubMed2007

G2019S mutation in the leucine-rich repeat kinase 2 gene is not associated with multiple system atrophy.

Multiple system atrophy (MSA) is characterized clinically by Parkinsonism, cerebellar dysfunction, and autonomic impairment. Multiple mutations in the LRRK2 gene are associated with parkinsonian disorders, and the most common one, the G2019S mutation, has been found in approximately 1% of sporadic cases of Parkinsonism. In a well-characterized cohort of 136 subjects with probable MSA and 110 neurologically evaluated control subjects, none carried the G2019S mutation. We conclude that the G2019S mutation in the LRRK2 gene is unlikely to be associated with MSA.

Cerebellum↗
PubMed1999

Multiple system atrophy.

Multiple system atrophy is a neurological disorder that has gone unrecognized for too long due to its involvement across multiple regions of the central nervous system. This disorder is finally being unveiled through increased reporting in the scientific literature. Further research will enhance our understanding of this disease and lead to more effective treatment regimens as well as an improved quality of life for patients with MSA.

Algorithms↗
PubMed1999

Multiple system atrophy.

Multiple system atrophy (MSA) is a degenerative central nervous system disease of unclear origin. Patients affected typically show symptoms attributable to the combined involvement of the extrapyramidal, pyramidal, cerebellar and autonomic nervous systems. At onset patients mostly see a doctor because of extrapyramidal or--more rarely--cerebellar symptoms. Evidence of autonomic nervous system involvement is often not apparent, at least to the neurologist, before the history is taken. In later stages, by contrast, involvement of all of the above systems is clinically detectable.

Humans↗
PubMed1997

Multiple system atrophy.

Multiple system atrophy (MSA) is a degenerative disease of the central nervous system with three components, usually variously expressed: nigrostriatal degeneration (NSD), olivopontocerebellar atrophy (OPCA) and Shy-Drager syndrome of autonomic system dysfunction (SDS). The clinical progression of MSA leads to death in a shorter time than in any of the components occurring separately. A common, and according to some authors, pathognomonic neuropathological finding in MSA cases is the presence of argyrophilic inclusions in the cytoplasm of glial cells, mainly oligodendrocytes, in the structures of the encephalon with most pronounced atrophic changes.

Disease Progression↗
PubMed2001

Multiple system atrophy.

Multiple system atrophy (MSA) is an adult-onset sporadic progressive neurodegenerative disorder of unknown etiology. It is clinically characterized by the variable combination of autonomic failure, parkinsonism, cerebellar ataxia, and pyramidal signs. The present review summarizes up-to-date knowledge on the clinical diagnosis and molecular pathology of MSA. We also review the role of additional investigations that may support a clinical diagnosis of MSA. Finally, we briefly discuss the management of MSA, focusing on possible future therapeutic strategies.

Central Nervous System↗
PubMed2005

Oxidative stress in transgenic mice with oligodendroglial alpha-synuclein overexpression replicates the characteristic neuropathology of multiple system atrophy.

Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterized by parkinsonism unresponsive to dopaminergic therapy, cerebellar ataxia, and dysautonomia. Neuropathology shows a characteristic neuronal multisystem degeneration that is associated with widespread oligodendroglial alpha-synuclein (alpha-SYN) inclusions. Presently no animal model completely replicates the specific neuropathology of MSA. Here we investigated the behavioral and pathological features resulting from oligodendroglial alpha-SYN overexpression in transgenic mice exposed to mitochondrial inhibition by 3-nitropropionic acid. In transgenic mice 3-nitropropionic acid induced or augmented motor deficits that were associated with MSA-like pathology including striatonigral degeneration and olivopontocerebellar atrophy. Widespread astrogliosis and microglial activation were also observed in the presence of alpha-SYN in oligodendrocytes. Our results indicate that combined mitochondrial inhibition and overexpression of oligodendroglial alpha-SYN generates a novel model of MSA that may be useful for evaluating both pathogenesis and treatment strategies.

Animals↗
PubMed2006

Cellular pathology in multiple system atrophy.

Multiple system atrophy (MSA) is a sporadic, adult-onset neurodegenerative disease, which is characterized by striatonigral degeneration, olivopontocerebellar atrophy, and preganglionic autonomic lesions in any combination. The histological hallmark is the presence of argyrophilic fibrillary inclusions in the oligodendrocytes, referred to as glial cytoplasmic inclusions (GCIs). Fibrillary inclusions are also found in the neuronal somata, axons, and nucleus. Neuronal cytoplasmic inclusions are frequently found in the pontine and inferior olivary nuclei. Since the discovery of alpha-synuclein as a major component of glial and neuronal inclusions in MSA, two neurodegenerative processes have been considered in this disease: one is due to the widespread occurrence of GCIs associated with oligodendroglia-myelin degeneration (oligodendrogliopathy) in the central nervous system, and the other is due to the filamentous aggregation of alpha-synuclein in the neurons in several brain regions. These two degenerative processes might synergistically cause neuronal depletion in MSA.

Animals↗
PubMed2005

Alpha B-crystallin is a major component of glial cytoplasmic inclusions in multiple system atrophy.

Multiple system atrophy (MSA) is characterized by the formation of oligodendroglial cytoplasmic inclusions (GCIs) consisting of alpha-synuclein filaments. AlphaB-crystallin, a small chaperone protein that binds to unfolded proteins and inhibits aggregation, has been documented in GCIs. We investigated the relative abundance and speciation of alphaB-crystallin in GCIs in MSA brains. We also examined the influence of alphaB-crystallin on the formation of cytoplasmic inclusions in cultured glial cells. Immunohistochemistry and confocal microscopy revealed alphaB-crystallin is a prominent component of GCIs, more abundant than in Lewy bodies in Lewy body dementia. One- and two-dimensional gel electrophoresis and mass spectrometric analysis of GCIs immunopurified from MSA brains indicated that alphaB-crystallin is a major protein component with multiple post-translationally modified species. In cultured C6 glioma cells treated with the proteasomal inhibitor, lactacystin, to induce accumulation of ubiquitinated proteins, a subset of cells showed increased cytoplasmic staining for alphaB-crystallin. Proteasome-inhibited cells transfected with GFP-tagged alpha-synuclein resulted in ubiquitin- and alphaB-crystallin-positive aggregates resembling GCIs in MSA brains. Our results indicate that alphaB-crystallin is a major chaperone in MSA, and suggest a role of the protein in the formation of inclusion bodies in glial cells.

Amino Acid Sequence↗
PubMed2004

Microglial activation parallels system degeneration in multiple system atrophy.

Multiple system atrophy (MSA) is a neurodegenerative disorder that predominantly affects motor-related neuroanatomic structures. The role of microglia in MSA is unknown. To address this issue, we conducted quantitative image studies on the brains from 13 cases of MSA, comprising 8 cerebellar and 5 parkinsonian variants. Microglial and glial cytoplasmic inclusion (GCI) burdens were determined with image analysis on brain sections immunostained with antibodies to HLA-DR and alpha-synuclein. Many activated microglia, as well as GCIs, were noted in motor-related structures, including the cerebellar input, extrapyramidal motor, and pyramidal motor structures, but not in the cerebellar output structures. This result indicates that microglial activation, as well as the distribution of GCIs, is system-specific in MSA. The correlation analysis between the microglial and GCI burdens yielded variable yet significant correlations in the cerebellar input, extrapyramidal motor, and pyramidal motor systems, but not in the cerebellar output system. This result suggests that microglial activation is at least partly determined by GCIs or oligodendroglial alpha-synuclein in specific neuroanatomic systems affected in MSA. Taken together, considering the known toxic effects of microglia in neurodegenerative diseases, microglia may play a part in the development of system-specific tissue injuries, contributing to the system-bound clinical and pathological phenotypes.

Aged↗
PubMed2000

[Changes in clinical diagnostic criteria for multiple system atrophy].

Multiple system atrophy (MSA) is a clinical and pathological entity characterized by the variable combination of autonomic failure, parkinsonism, cerebellar and pyramidal signs and by cell loss with gliosis and oligodendroglial cytoplasmic inclusions in the nigrostriatal, olivopontocerebellar systems and the spinal cord. Beyond nosology there has been a need for reliable clinical diagnosis criteria for MSA. Such criteria should ideally combine good sensitivity and specificity to diagnose MSA at different stages and should be good predictors (high positive predictive value) of the pathological diagnosis. Difficulties encountered in establishing MSA clinical diagnosis criteria were, among others, the variable expression of the disease, the definition of autonomic failure, of the cerebellar syndrome and of the poor levodopa response of parkinsonism. Quinn in 1989 proposed 3 sets of criteria (revised in 1994) to diagnose "possible", "probable" and "definite" MSA. These criteria are quite simple and partially validated. More recently these criteria evolved towards consensus criteria in which autonomic failure had a more central position. The consensus conference, held in 1998, proposed a precise definition of the various clinical domains and the combination needed for the clinical diagnosis, as well as exclusion criteria. In this article, we review and comment the different criteria for the clinical diagnosis of MSA.

Autonomic Nervous System Diseases↗
PubMed2005

Animal models of multiple system atrophy.

Multiple system atrophy (MSA) is a fatal neurodegenerative disorder presenting with autonomic failure and motor impairment, primarily comprising L-dopa-resistant parkinsonism but occasionally involving cerebellar ataxia. These features result from progressive multisystem neuronal loss that is associated with oligodendroglial alpha-synuclein inclusions. The growing number of animal models for MSA reflects the search for a preclinical test-bed for elucidating MSA pathogenesis and for developing novel therapeutic interventions. Here, the currently available MSA animal models will be reviewed and leads for future research will be identified.

Animals↗
PubMed2000

[Sleep apnea in multiple system atrophy].

Multiple system atrophy(MSA) characterized clinically by any combination of autonomic, extrapyramidal or cerebellar symptoms and signs. MSA patients frequently manifest a variety of sleep-related respiratory disturbances, which are life threatening problems. Above all, a common and serious complication is upper-airway obstructive sleep apnea associated with stridor, which is caused by vocal cord abductor paralysis(VCAP). For the early diagnosis of VCAP, it is important to perform laryngoscopy during sleep, because VCAP does not appear during awakefulness in the early stage of MSA. Polysomnographic study should be obtain to assess the severity of respiratory disturbances. Tracheostomy is reliable treatment for respiratory disturbances due to VCAP, while nasal continuous positive pressure may be a useful treatment for some patients.

Humans↗
PubMed2005

In vivo models of multiple system atrophy.

Multiple system atrophy (MSA) is a sporadic adult-onset neurodegenerative disorder of unknown etiology clinically characterized by a combination of parkinsonian, pyramidal, and cerebellar signs. Levodopa-unresponsive parkinsonism is present in 80% of MSA cases, and this dominant clinical presentation (MSA-P) is associated with a combined degeneration of the substantia nigra pars compacta and the striatum in anatomically related areas. The limited knowledge of the pathophysiology of MSA and the lack of therapeutic strategies prompted the development of lesion models reproducing striatonigral degeneration, the substrate of levodopa-unresponsive parkinsonism in MSA-P. This method was carried out first in rats with two different stereotaxic strategies using either two neurotoxins ("double toxin-double lesion") or a single neurotoxin ("single toxin-double lesion"). Double-lesioned rat models showed severe motor impairment compared to those with a single nigral or striatal lesion and helped to mimic different stages of the disease. Systemic models were also developed in mice and primates using the nigral toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and the striatal toxin 3-nitropropionic (3-NP). In mice, although MPTP reduced the subsequent sensitivity to 3-NP in a sequential lesion, simultaneous nigral and striatal insults were shown to exacerbate striatal damage. MPTP-treated monkeys displayed a significant worsening of parkinsonism and a loss of levodopa-responsiveness after the appearance of hindlimb dystonia and striatal lesion formation induced by subsequent 3-NP intoxication. The different species and intoxication paradigms used will be useful to investigate functional changes in substantia nigra and striatum and to define neuroprotective, neurorestorative, or symptomatic therapeutic strategies.

Animals↗
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↗
PubMed2002

The symptomatic treatment of multiple system atrophy.

Multiple system atrophy (MSA) is a neurodegenerative disease of undetermined aetiology that occurs sporadically and manifests itself as a combination of parkinsonian, autonomic, cerebellar and pyramidal signs. Despite the lack of any effective therapy to reverse this condition, some of the symptoms may be, at least temporarily, improved with adequate symptomatic therapies. Medical treatment is largely aimed at mitigating the parkinsonian and autonomic features. The therapeutic results of levodopa therapy in cases of MSA are difficult to interpret because of their variability. Nevertheless, the statement that patients with MSA are non or poorly levodopa-responsive is misleading. Clinical and pathologically proven series document about 40-60% levodopa efficacy in patients with MSA presenting with predominant parkinsonian features. Unfortunately, other antiparkinsonian compounds (dopamine agonists, amantadine) are not more effective than levodopa. Orthostatic hypotension (OH) can be suspected from the patient's history and subsequently documented in the clinic by measuring lying and standing blood pressure. The diagnosis ideally should be confirmed in the laboratory with additional tests to determine the cause and evaluate the functional deficit, so as to aid treatment. A variety of pharmacological agents with different mechanisms of action have been used in MSA to reduce OH when this is symptomatic. OH can also be alleviated by avoiding aggravating factors, such as the effects of food, micturition, exposure to a warm environment and physiological diurnal changes and by using other non-pharmacological strategies. The treatment of the very common genito-urinary symptoms (incontinence, retention, impotence) should also be considered in order to improve the quality of life of these patients.

Autonomic Nervous System Diseases↗