SEARCH · PubMed Health

Results for “Multiple System Atrophy”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,243 records · Page 69Linked to original sources

PubMed2005

A definition of Parkinson's disease.

We are now entering a period when the process of unraveling the puzzles of 'Parkinson's Disease' has generated a mass of information that does not fit into our traditional concepts. Having split off 'Progressive Supranuclear Palsy' and 'Multiple System Atrophy', we are faced with the dilemma of what to do with the various forms of Parkinsonism caused by a number of different mutations, and how to interpret pathological heterogeneity. Faced with these new questions, it is time to reconsider how 'Parkinson's Disease' is to be defined.

Humans↗

PubMed2006

Spatial topography of the neurofibrillary tangles in cortical and subcortical regions in progressive supranuclear palsy.

OBJECTIVE: To study the topography of neurofibrillary tangles (NFT) in cortical and subcortical areas in progressive supranuclear palsy (PSP). METHODS: Pattern analysis was carried out on tau-positive NFT in eight PSP cases. RESULTS: Of the areas studied, NFT were randomly distributed in 68%, regularly distributed in 3%, and clustered in 29%. A regular distribution of clusters was more frequent in cortical than subcortical areas. CONCLUSION: NFT topography in subcortical areas was similar to inclusions in the synucleinopathy multiple system atrophy (MSA) but in cortical areas was comparable to other tauopathies.

Aged↗

PubMed2004

An overview of parkinsonian syndromes: data from the literature and from an Italian data-base.

Recent molecular biology research on neurodegenerative diseases, including parkinsonisms, has identified mutations in the genes that code for the proteins alpha-synuclein and tau, which have been used to classify them into synucleinopathies and tauopathies. The synucleinopathies include, besides the most common and well studied Parkinson's disease (PD), dementia with Lewy bodies, which accounts for approximately 20% of all cases of dementia in the elderly, and multiple system atrophy, whereas the tauopathies include rare and rapidly progressive syndromes, such as progressive supranuclear palsy and corticobasal degeneration. Data we collected at our center in over 2900 parkinsonian patients show that PD accounts for no more than 70% of parkinsonisms. The various syndromes have many features in common that make the differential diagnosis difficult in the early stages of disease. Our data are consistent with the findings reported in the international literature and provide additional information useful for differential diagnosis.

Aged↗

PubMed2005

Excessive daytime sleepiness in parkinsonism.

Excessive daytime sleepiness (EDS) can affect 20-50% of patients with Parkinson's disease (PD), whereas sleep attacks (SA), which are sleep episodes without prodroma, seem infrequent. EDS is associated with more advanced disease, higher doses of levodopa-equivalent, and sometimes the use of dopamine agonists. Patients at risk for SA have higher Epworth sleepiness scores (ESS) (although an important subset of patients under-score on this scale) and a more frequent use of ergot or non-ergot dopamine agonists. Polysomnography is a valuable tool in patients with PD, because sleep apnea may occur in 20% of patients, whereas a specific narcolepsy-like phenotype, identified on multiple-sleep latency tests, occurs in patients with most severe EDS; this suggests a lesion in sleep-wake systems. Removal or replacement of a recently introduced dopamine agonist may offer some relief for EDS. If not, the adjunction of modafinil has a good benefit-risk ratio in patients with PD. EDS (and sometimes the narcolepsy-like phenotype) may also affect patients with atypical parkinsonism, such as dementia with Lewy bodies, multiple-system atrophy, and progressive supranuclear palsy.

Antiparkinson Agents↗

PubMed2007

Transcranial brain parenchyma sonography in movement disorders: state of the art.

The present paper summarizes recommendations on transcranial sonography (TCS) application in neurodegenerative diseases, resulting from a consensus meeting of the European Society of Neurosonology and Cerebral Hemodynamics. TCS of distinct infra- and supratentorial brain structures detects characteristic changes in several movement disorders, such as abnormal hyperechogenicity of substantia nigra (SN) in Parkinson's disease and of lenticular nucleus in dystonia, Wilson's disease and atypical Parkinsonian disorders. In healthy adults, the TCS finding of marked SN hyperechogenicity indicates a subclinical functional impairment of the nigrostriatal dopaminergic system. The finding of marked SN hyperechogenicity in combination with normal lenticular-nucleus echogenicity discriminates idiopathic Parkinson's disease from multiple-system atrophy and progressive supranuclear palsy with a positive predictive value of more than 90%. As TCS is a quick and noninvasive method, using the same duplex-ultrasound machines as for investigation of intracranial vessels, applicable even in agitated patients, this method has a great potential to be more widely used.

Humans↗

PubMed2000

Widespread nitration of pathological inclusions in neurodegenerative synucleinopathies.

Reactive nitrogen species may play a mechanistic role in neurodegenerative diseases by posttranslationally altering normal brain proteins. In support of this hypothesis, we demonstrate that an anti-3-nitrotyrosine polyclonal antibody stains all of the major hallmark lesions of synucleinopathies including Lewy bodies, Lewy neurites and neuraxonal spheroids in dementia with Lewy bodies, the Lewy body variant of Alzheimer's disease, and neurodegeneration with brain iron accumulation type 1, as well as glial and neuronal cytoplasmic inclusions in multiple system atrophy. This antibody predominantly recognized nitrated alpha-synuclein when compared to other in vitro nitrated constituents of these pathological lesions, such as neurofilament subunits and microtubules. Collectively, these findings imply that alpha-synuclein is nitrated in pathological lesions. The widespread presence of nitrated alpha-synuclein in diverse intracellular inclusions suggests that oxidation/nitration is involved in the onset and/or progression of neurodegenerative diseases.

Adult↗

PubMed2002

Tyrosine 125 of alpha-synuclein plays a critical role for dimerization following nitrative stress.

alpha-Synuclein is a major component of Lewy bodies in Parkinson's disease, dementia with Lewy bodies, and glial cytoplasmic inclusions in multiple system atrophy. Increasing evidence suggests that the nitration of tyrosine residues in alpha-synuclein induced by oxidative injury is involved in the formation of inclusions characteristic to these synucleinopathies. Exposure of alpha-synuclein to peroxynitrite induces nitration of tyrosine residues, thereby forming alpha-synuclein oligomers. However, the contribution of tyrosine residues to either the nitration or the oligomerization is currently unknown. The present study used recombinant wild-type and mutant alpha-synuclein proteins to investigate the role of each alpha-synuclein tyrosine residue in the in vitro formation of alpha-synuclein oligomers under nitrative stress. Confocal microscopic analysis revealed that wild-type alpha-synuclein protein was able to accumulate and form an inclusion-like structure in the cytoplasm of living cells upon introduction by streptolysin O. Authentic peroxynitrite induced nitration of tyrosine residues in alpha-synuclein protein, as well as dimerization of alpha-synuclein. The formation of both SDS- and heat-stable dimers suggests cross-linking between nitrated tyrosine residues. Nonetheless, dimerization of alpha-synuclein proteins lacking tyrosine 125 was significantly decreased compared with alpha-synuclein proteins lacking tyrosine residues at positions 39, 133, or 136. Presumably, tyrosine 125 plays a critical role for alpha-synuclein dimerization under nitrative stress.

DNA, Complementary↗

PubMed2000

Immunohistochemical localization of glial cell line-derived neurotrophic factor family receptor alpha-1 in the rat brain: confirmation of expression in various neuronal systems.

The localization of glial cell line-derived neurotrophic factor (GDNF) family receptor alpha-1 (GFRalpha-1) was investigated in rat brain by immunohistochemistry using a polyclonal antibody against a specific sequence of the rat protein. For raising the antisera in rabbits, we synthesized the oligopeptide SDVFQQVEHISKGN that corresponds to residues 139 to 152 of rat GFRalpha-1. On immunospot assay, 0.5 microg/ml of an affinity-purified antibody was capable of detecting 7.8 pmol of the rat GFRalpha-1 oligopeptides. When rat brain homogenates were examined by Western blots, the antibody revealed two main bands with molecular weights of approximately 47 kDa and 53 kDa, corresponding to the known sizes of GFRalpha-1. Immunohistochemistry in rat brain demonstrated that GFRalpha-1-like immunoreactivity was present in neurons but not in glial cells. The localization of GFRalpha-1-like immunoreactivity was largely consistent with that of the corresponding GFRalpha-1 mRNA. Positive neurons were distributed widely in various brain regions, but were particularly abundant in such regions as the olfactory bulb, diagonal band, substantia innominata, zona incerta, substantia nigra, cerebellar cortex, nuclei of the cranial nerves including auditory system and spinal motoneurons. The present study showed that GFRalpha-1 in the normal central nervous system is expressed preferentially in certain multiple neuronal systems that include cholinergic system as well as dopaminergic system and motor neurons. As GFRalpha-1 protein was found in numerous brain structures, GDNF family ligands may have therapeutic application not only in degenerative diseases affecting in specific nervous systems, such as Parkinson's disease, amyotrophic lateral sclerosis and multiple system atrophy, but in diffusely damaging diseases like cerebrovascular diseases.

Animals↗

PubMed2002

Amino acid determinants of alpha-synuclein aggregation: putting together pieces of the puzzle.

Parkinson's disease is the second most common neurodegenerative disease, and results from loss of dopaminergic neurons in the substantia nigra. The aggregation and fibrillation of alpha-synuclein in the form of intracellular proteinaceous aggregates (Lewy bodies and Lewy neurites) have been implicated as a causative factor in this disease, as well as in several other neurodegenerative disorders, including dementia with Lewy bodies, Lewy body variant of Alzheimer's disease, multiple system atrophy and Hallervorden-Spatz disease. Thus, the aggregated forms of alpha-synuclein play a crucial role in the pathogenesis of the synucleinopathies. However, the molecular mechanisms underlying alpha-synuclein aggregation into specific filamentous inclusions remained unknown until recently. Data on the aggregation and fibrillation properties of human alpha-, beta- and gamma-synucleins, mouse alpha-synuclein and familial Parkinson's disease mutants of human alpha-synuclein (A30P and A53T) are analyzed in order to shed light on the amino acid determinants of synuclein aggregation.

Amino Acid Sequence↗

PubMed1996

Plasma sulfoconjugated dopamine levels are normal in patients with autonomic failure.

Plasma levels of norepinephrine (NE), dihydroxyphenylglycol (DHPG), dihydroxyphenylalanine (DOPA), dopamine (DA), and dihydroxyphenylacetic acid (DOPAC)--all of which are free catechols--and sulfoconjugated DA (DASO4) were determined in 14 normal subjects and 18 patients with neurogenic orthostatic hypotension caused by either multiple system atrophy (MSA) (n = 11) or pure autonomic failure (n = 7). All free catechols were normal in patients with MSA, whereas NE, DHPG, DA, and DOPAC levels were significantly lower in patients with pure autonomic failure. The levels of DA-SO4, however, did not statistically differ among the three groups. The different plasma levels of free catechols in MSA and pure autonomic failure are consistent with the view that peripheral sympathetic neurons are relatively preserved in MSA, whereas they are severely affected in pure autonomic failure. Because DASO4 does not appear to be affected in pure autonomic failure, it appears likely that this metabolite is derived mainly from non-neural sources, such as the gastrointestinal tract, rather than from the sympathoadrenomedullary system.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2000

The involvement of the neuronal Golgi apparatus and trans-Golgi network in the human olivary hypertrophy.

We studied the Golgi apparatus (GA) and trans-Golgi network (TGN) in the human olivary hypertrophy by immunohistological methods with organelle specific antibodies against the medial cisternae of the organelle (MG160) and the trans-Golgi network (TGN46). The GA and TGN of enlarged neurons in the inferior olivary nuclei in the early stages after central tract lesions lost the normal network-like configuration, and they were reduced to numerous small disconnected granules (fragmentation). In chronic stages after lesions, the GA and TGN of vacuolated or enlarged neurons showed a variety of morphological profiles, such as normal-looking patterns, fragmentation, reduction in number, and aggregation around nuclei or at a distance in the cytoplasm. In patients with multiple system atrophy, the GA and TGN of the neurons in the inferior olivary nuclei showed almost similar findings to those seen in the chronic stages after brainstem lesions. These results suggest that the GA and TGN are affected in degenerating neurons by anterograde transneuronal mechanisms.

Aged↗

PubMed2001

REM sleep behavior disorder in sleep-disordered patients with versus without Parkinson's disease: is there a need for polysomnography?

We reviewed the polysomnograms (PSGs) of 292 consecutive patients with sleep disorders (Parkinson's disease (PD), n=19, other sleep disorders, n=273) to investigate the sensitivity and specificity of the clinical diagnosis of rapid eye movement behavior disorder (RBD) compared with polysomnographic diagnosis. Patients with dementia, multiple system atrophy, or any other neurodegenerative disease were excluded. RBD was diagnosed clinically if the minimal criteria, according to the guidelines given in the International Sleep Disorders Classification, were fulfilled. The following PSG criteria were required for diagnosis of RBD: REM sleep without muscle atonia seen in PSG associated with motor behavior visible in the PSG-synchronized videotape. Nine of nineteen PD patients (47%) had RBD. RBD occurred in only four patients without PD (1.8%). The sensitivity of specialized interviews for identifying RBD clinically was good in non-PD patients (sensitivity: 100%, specificity: 99.6%). However, the sensitivity was poor (33%) with a specificity of 90%, in patients with PD. We conclude that the diagnosis of RBD in patients with PD requires PSG, whereas interviews are sufficient for diagnosing RBD in non-PD patients.

Aged↗

PubMed1998

Disorders of excessive daytime sleepiness--an update.

Disorders of excessive daytime sleepiness (EDS) constitute a major health hazard, since impaired alertness may lead to accidents and poor quality of life, and some of them are associated with increased cardiovascular morbidity and mortality. Many disorders of EDS are neurological diseases (e.g. narcolepsy and periodic limb movements in sleep, PLMS). The largest group of disorders causing EDS consists of sleep-related disturbances of breathing, where neuroregulatory mechanisms play a major role in pathophysiology. Many patients with neurodegenerative and neuromuscular diseases suffer from sleep disturbances associated with EDS. Therefore, neurologists must be acquainted with the differential diagnosis of EDS and the major categories of sleep disorders causing it. The present update focuses on major sleep disorders causing EDS, and approaches the topic from the neurologist's perspective. Rather than being an extensive review, this update includes recent data on epidemiology, pathophysiology, diagnosis and treatment of obstructive sleep apnea and related conditions (increased upper airway resistance syndrome, central sleep apnea), as well as of narcolepsy and PLMS. Also included are recent data concerning EDS in neurodegenerative (Alzheimer's disease, Parkinson's disease, multiple system atrophy) and neuromuscular disorders.

Central Nervous System Diseases↗

PubMed1993

The central autonomic network: functional organization, dysfunction, and perspective.

The central autonomic network (CAN) is an integral component of an internal regulation system through which the brain controls visceromotor, neuroendocrine, pain, and behavioral responses essential for survival. It includes the insular cortex, amygdala, hypothalamus, periaqueductal gray matter, parabrachial complex, nucleus of the tractus solitarius, and ventrolateral medulla. Inputs to the CAN are multiple, including viscerosensory inputs relayed on the nucleus of the tractus solitarius and humoral inputs relayed through the circumventricular organs. The CAN controls preganglionic sympathetic and parasympathetic, neuroendocrine, respiratory, and sphincter motoneurons. The CAN is characterized by reciprocal interconnections, parallel organization, state-dependent activity, and neurochemical complexity. The insular cortex and amygdala mediate high-order autonomic control, and their involvement in seizures or stroke may produce severe cardiac arrhythmias and other autonomic manifestations. The paraventricular and other hypothalamic nuclei contain mixed neuronal populations that control specific subsets of preganglionic sympathetic and parasympathetic neurons. Hypothalamic autonomic disorders commonly produce hypothermia or hyperthermia. Hyperthermia and autonomic hyperactivity occur in patients with head trauma, hydrocephalus, neuroleptic malignant syndrome, and fatal familial insomnia. In the medulla, the nucleus of the tractus solitarius and ventrolateral medulla contain a network of respiratory, cardiovagal, and vasomotor neurons. Medullary autonomic disorders may cause orthostatic hypotension, paroxysmal hypertension, and sleep apnea. Neurologic catastrophes, such as subarachnoid hemorrhage, may produce cardiac arrhythmias, myocardial injury, hypertension, and pulmonary edema. Multiple system atrophy affects preganglionic autonomic, respiratory, and neuroendocrine outputs. The CAN may be critically involved in panic disorders, essential hypertension, obesity, and other medical conditions.

Brain↗

PubMed2003

Part II: alpha-synuclein and its molecular pathophysiological role in neurodegenerative disease.

Alpha-synuclein (alphaSN) brain pathology is a conspicuous feature of several neurodegenerative diseases. These include prevalent conditions such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), and the Lewy body variant of Alzheimer's disease (LBVAD), as well as rarer conditions including multiple systems atrophy (MSA), and neurodegeneration with brain iron accumulation type-1 (NBIA-1). Common in these diseases, some referred to as alpha-synucleinopathies, are microscopic proteinaceous insoluble inclusions in neurons and glia that are composed largely of fibrillar aggregates of alphaSN. This molecular form of alphaSN contrasts sharply with normal alphaSN, which is an abundant soluble presynaptic protein in brain neurons. alphaSN is a highly conserved protein in vertebrates and only seven of its 140 amino acids differ between human and mouse. Flies lack an alphaSN gene. Implicated in neurotoxicity are two alphaSN mutants (A53T and A30P) that cause extremely rare familial forms of PD, alphaSN fibrils and protofibrils, soluble protein complexes of alphaSN with 14-3-3 protein, and phosphorylated, nitrosylated, and ubiquitylated alphaSN species. Unlike rare forms of fPD caused by mutations in alphaSN, disease mechanisms in most alpha-synucleinopathies implicate wildtype alphaSN and seem to converge around oxidative damage and impairments in protein catabolism. It is not known whether these causalities involve alphaSN from the beginning, but defects in the handling of this protein seem to contribute to disease progression because accumulation of toxic alphaSN forms damage neurons. Here, we summarize the main structural features of alphaSN and its functions, and discuss the molecular alphaSN species implicated in human disease and transgenic animal models of alpha-synucleinopathy in fly and rodents.

Alzheimer Disease↗

PubMed2005

[Animal models of parkinsonism].

Research into the pathophysiology of Parkinson's disease has been rapidly advanced by the development of animal models. Initial models were developed by using toxins that specifically targeted dopamine neurons, the most successful of which used 6-hydroxydopamine in rats and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice and primates. Their combination with specific striatal toxins, such as quinolinic acid or 3-nitropropionic acid, has led to the development of experimental models replicating the salient pathological and clinical features of multiple system atrophy of the striatonigral degeneration subtype both in rodents and primates. More recently, the identification of alpha-synuclein gene mutations in rare familial cases of Parkinson's disease has led to the development of alpha-synuclein knock-out and transgenic animals. We conclude that the use and improvement of both phenotypic and genetic models can significantly speed progress toward understanding the pathophysiology of these devastating diseases and finding innovative cures.

Animals↗

PubMed2006

[Idiopathic chronic dysautonomia: when should the diagnosis be made?].

INTRODUCTION: Chronic autonomic disorders may complicate a wide range of conditions which can be divided into secondary, due to specific diseases, and primary, in which no cause has been determined. CASE REPORT: We report the case of a 43-year-old woman, who presented a chronic autonomic failure, which had begun by symptomatic orthostatic hypotension. Progressively, syncopes became daily, causing considerable discomfort associated with other signs of sympathic dysfunction: unilateral Horner's syndrome, diarrhea and hypohidrosis. The autonomic involvement was confirmed by study of the cardiovascular responses to tilt-up and electrophysiological autonomic testing. Etiologic search for a chronic acquired neuropathy (diabetes, amyloidis, paraneoplastic) or an inherited neuropathy was not conclusive. After five years, dysautonomic symptoms increased, but remained isolated. The physical examination did not show other clinical abnormalities such as cerebellar, pyramidal or extrapyramidal failure in favor of a multiple system atrophy or Parkinson's disease. All these data suggest the diagnosis of a primary autonomic failure. CONCLUSION: The diagnosis of primary autonomic failure is difficult to make because it requires that all the investigations in search of an etiology are negative and a long follow-up to be sure that dysautonomic symptoms persist isolated after many years of progression.

Adult↗

PubMed1988

Noradrenaline response to edrophonium in primary autonomic failure: distinction between central and peripheral damage.

The effects of intravenous edrophonium on plasma noradrenaline were studied in 12 subjects with primary autonomic failure. 5 had clinical features of central autonomic damage, 4 with parkinsonism (PD) and 1 with multiple system atrophy (MSA); the other 7 had clinical features of progressive autonomic failure without detectable central neurological damage (PAF). After edrophonium all but 1 subject showed falls in heart rate of about 6 beats/min; there were no consistent blood pressure changes. The 5 PD/MSA patients all had normal plasma noradrenaline responses to edrophonium, with rises of 35-66% within 2-8 min of injection. 6 of the 7 PAF patients had no response or very small responses (-6 to +11%), while the other subject had a normal response (70% rise). The noradrenaline response to edrophonium may provide a simple way to differentiate between central and peripheral autonomic damage.

Aged↗