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Results for “Multiple System Atrophy”

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PubMed2003

Nucleus-specific alteration of raphe neurons in human neurodegenerative disorders.

Neurodegenerative diseases share symptoms suggested to be related to the serotonergic system. To evaluate the involvement of serotonergic raphe nuclei, we compared the percentage of neurons synthesizing serotonin in the nucleus centralis superior (NCS), raphe obscurus and pallidus (NROP) in Alzheimer's disease (AD), progressive supranuclear palsy (PSP), Parkinson's disease (PD), multiple system atrophy (MSA), and control brains. We used immunohistochemistry for tryptophan hydroxylase (TpOH), phosphorylated tau, and alpha-synuclein. We observed a significant decrease in the NCS in the NROP in AD, but a significant increase in PSP and MSA. Cytoskeletal pathology was present in the NCS and NROP to a variable degree. We conclude that there is disease- and nucleus-specific alteration of serotonin synthesis in the raphe.

Aged↗

PubMed2000

Multiple system atrophy/progressive supranuclear palsy: alpha-Synuclein, synphilin, tau, and APOE.

Article abstract-Alpha synuclein, tau, synphilin, and APOE genotypes were analyzed in patients with multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) and controls. The predisposing effect of the tau insertion polymorphism to the development of PSP is confirmed. However, no effect of alpha-synuclein, synphilin, or APOE variability on the development of PSP, or of tau, alpha-synuclein, APOE, or synphilin gene variability on the development of MSA, are demonstrated.

Apolipoproteins E↗

PubMed2002

Idiopathic rapid eye movement sleep behavior disorder is a harbinger of dementia with Lewy bodies.

Idiopathic rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia clinically linked with the alpha-synucleinopathies multiple systems atrophy (MSA), Parkinson's disease (PD), and dementia with Lewy bodies (DLB). Available autopsy information is limited but suggests that the pathologic basis of idiopathic RBD may be neuronal loss and Lewy bodies in pigmented monoaminergic nuclei, including the locus coeruleus and substantia nigra, which project to pontine nuclei mediating atonia during REM sleep. Thus, idiopathic RBD may be an alpha-synucleinopathy per se and a harbinger of impending PD, DLB, or MSA. Inclusion of historical or concurrent idiopathic RBD in the diagnostic criteria for DLB may improve their sensitivity, specificity, and clinical utility.

Aged↗

PubMed2000

Oxidative damage linked to neurodegeneration by selective alpha-synuclein nitration in synucleinopathy lesions.

Aggregated alpha-synuclein proteins form brain lesions that are hallmarks of neurodegenerative synucleinopathies, and oxidative stress has been implicated in the pathogenesis of some of these disorders. Using antibodies to specific nitrated tyrosine residues in alpha-synuclein, we demonstrate extensive and widespread accumulations of nitrated alpha-synuclein in the signature inclusions of Parkinson's disease, dementia with Lewy bodies, the Lewy body variant of Alzheimer's disease, and multiple system atrophy brains. We also show that nitrated alpha-synuclein is present in the major filamentous building blocks of these inclusions, as well as in the insoluble fractions of affected brain regions of synucleinopathies. The selective and specific nitration of alpha-synuclein in these disorders provides evidence to directly link oxidative and nitrative damage to the onset and progression of neurodegenerative synucleinopathies.

Alzheimer Disease↗

PubMed2003

[Dopaminergic treatment and parkinsonian syndromes].

Chronic dopamine treatment usually provides partial and temporary improvement of extrapyramidal signs in about 40p.cent of the patients with multiple system atrophy. Exceptionally, dopamine agonists may provide a significant and persistent improvement in progressive supranuclear palsy. For patients with Lewy body dementia, levodopa often provides a significant improvement of the extrapyramidal syndrome in about 70p.cent of the treated patients. Dopamine treatment generally has no effect on secondary extrapyramidal syndromes caused by vascular parkinsonism or neuroleptics. Antiparkinsonian treatment can cause several complications, particularly degenerative parkinsonian syndromes with an increased frequency of cognitive disorders and dysautonomia. Consequently, antiparkinsonian agents should only be proposed within the framework of a differential diagnosis between parkinsonism and idiopathic Parkinson's disease then continued only if the risk/benefit ratio, systematically evaluated for each patient, is favorable.

Diagnosis, Differential↗

PubMed2004

Pael-R is accumulated in Lewy bodies of Parkinson's disease.

We examined the distribution of Pael-R, a newly identified substrate for Parkin, in Parkinson's disease (PD) and multiple system atrophy (MSA). Pael-R, Parkin, alpha-synuclein, and ubiquitin accumulated in Lewy bodies (LBs) and neurites. Pael-R was localized in the core of LBs. Parkin and alpha-synuclein accumulated in the halo, neuronal cell bodies, and processes. These findings potentially suggest the involvement of Pael-R in LB formation, and protection role of Parkin in Pael-R-mediated neurotoxicity in PD. The absence of Pael-R and Parkin in glial cytoplasmic inclusions (GCIs) in MSA implies a distinct pathway involved in the formation of LBs and GCIs.

Aged↗

PubMed2004

Fragile X premutation alleles in SCA, ET, and parkinsonism in an Asian cohort.

Among 367 subjects, the authors analyzed 167 patients with essential tremor, sporadic progressive cerebellar ataxia, multiple-system atrophy, and atypical parkinsonism and 200 healthy control subjects for FMR1 premutation alleles. None of the subjects carried alleles within the premutation range. These findings suggest that in the absence of other supportive clinical or imaging features, the cost-effectiveness of routine fragile X tremor/ataxia syndrome screening in this Asian cohort with movement disorders was low.

Adult↗

PubMed1999

Neuritic sprouting with aberrant expression of the nitric oxide synthase III gene in neurodegenerative diseases.

Neuronal loss, synaptic disconnection and neuritic sprouting correlate with dementia in Alzheimer's disease (AD). Nitric oxide (NO) is an important synaptic plasticity molecule generated by nitric oxide synthase (NOS) oxidation of a guanidino nitrogen of L-arginine. Experimentally, the NOS III gene is modulated with neuritic sprouting. In a previous study, NOS III expression was found to be abnormal in cortical neurons, white matter glial cells, and dystrophic neurites in AD and Down syndrome brains. The present study demonstrates the same abnormalities in neuronal and glial NOS III expression with massive proliferation of NOS III-immunoreactive neurites and glial cell processes in other neurodegenerative diseases including: diffuse Lewy body disease, Pick's disease, progressive supranuclear palsy, amyotrophic lateral sclerosis, multiple system atrophy, and Parkinson's disease. However, each disease, including AD, was distinguished by the selective alterations in NOS III expression and sprouting in structures marred by neurodegeneration. Double label immunohistochemical staining studies demonstrated nitrotyrosine and NOS III co-localized in only rare neurons and neuritic sprouts, suggesting that peroxynitrite formation and nitration of growth cone proteins may not be important consequences of NOS III enzyme accumulation. The results suggest that aberrant NOS III expression and NOS III-associated neuritic sprouting in the CNS are major abnormalities common to several important neurodegenerative diseases.

Aged↗

PubMed2003

Isofurans, but not F2-isoprostanes, are increased in the substantia nigra of patients with Parkinson's disease and with dementia with Lewy body disease.

F2-isoprostanes (F2-IsoPs) are well-established sensitive and specific markers of oxidative stress in vivo. Isofurans (IsoFs) are also products of lipid peroxidation, but in contrast to F2-IsoPs, their formation is favored when oxygen tension is increased in vitro or in vivo. Mitochondrial dysfunction in Parkinson's disease (PD) may not only lead to oxidative damage to brain tissue but also potentially result in increased intracellular oxygen tension, thereby influencing relative concentrations of F2-IsoPs and IsoFs. In this study, we attempted to compare the levels of F2-IsoPs and IsoFs esterified in phospholipids in the substantia nigra (SN) from patients with PD to those of age-matched controls as well as patients with other neurodegenerative diseases, including dementia with Lewy body disease (DLB), multiple system atrophy (MSA), and Alzheimer's disease (AD). The results demonstrated that IsoFs but not F2-IsoPs in the SN of patients with PD and DLB were significantly higher than those of controls. Levels of IsoFs and F2-IsoPs in the SN of patients with MSA and AD were indistinguishable from those of age-matched controls. This preferential increase in IsoFs in the SN of patients with PD or DLB not only indicates a unique mode of oxidant injury in these two diseases but also suggests different underlying mechanisms of dopaminergic neurodegeneration in PD and DLB from those of MSA.

Aged↗

PubMed2000

Abnormalities of motor cortical excitability are not correlated with clinical features in atypical parkinsonism.

OBJECTIVE: To evaluate the specificity of motor cortical excitability changes in parkinsonian syndromes and their relevance to the pathophysiology of cardinal parkinsonian features. METHODS: Paired transcranial magnetic stimulation (TMS) was used to assess cortico-cortical inhibition (CCI) and facilitation (CCF) in the opponens pollicis muscle of patients with atypical, non-L-dopa- (LD) responsive parkinsonism. RESULTS: Compared with age-matched normal control subjects, CCI (interstimulus interval [ISI], 3 ms) was significantly reduced in 10 patients with predominantly parkinsonian multiple system atrophy (MSA-P) and in seven with vascular parkinsonism (VP), but not in four with predominantly cerebellar MSA. No significant change of CCF (ISI, 12 ms) was observed. No correlation was found between the amount of CCI and clinical status as evaluated with the Unified Parkinson's Disease Rating Scale (UPDRS). In 10 patients (5 MSA-P, 5 VP), CCI was significantly increased by LD acute administration without concurrent clinical changes. CONCLUSIONS: Abnormalities of CCI are not peculiar to idiopathic Parkinson's disease and seem unlikely to underlie any specific parkinsonian feature, but rather possibly reflect a nonspecific imbalance of inhibitory and facilitatory motor cortical circuits.

Adult↗

PubMed2005

[MSA update].

Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder characterized by various combinations of parkinsonism, cerebellar ataxia and autonomic failure. Although the clinical entities of olivopontocerebellar atarophy (OPCA), striatonigral degneratin (SND) and Shy-Drager syndrome have been conventionally used, recent identification of oligodendroglial cytoplasmic inclusions (GCIs) as the pathognomonic findings has established the clinicopathological entity of MSA. Epidemiological studies in Japan have shown that MSA is the most common form of sporadic ataxia. Among the various clinical forms of MSA, OPCA has been shown to be the most common form. Although MSA has been regarded as a sporadic disease, familial occurrence has recently been identified. Integrated analyses of non-parametric linkage analyses on the familial MSA cases and association studies on sporadic MSA cases are expected to accelerate the studies on identification of genes involved in the pathogenesis of MSA.

Humans↗

PubMed1999

[Functional imaging for disorders of basal ganglia].

The nigrostriatal dopaminergic function and regional glucose metabolism were evaluated in patients suffering from various disorders of basal ganglia by using positron emission tomography with 18F-dopa and 18F-FDG, respectively. The 18F-dopa uptake in the striatum (the caudate head and the putamen) decreased in patients with Parkinson's disease but was relatively unaffected in the caudate. The cerebral glucose metabolism was normal in patients with Parkinson's disease. The 18F-dopa uptake in the striatum also decreased in cases of multiple system atrophy and progressive supranuclear palsy, but there was no difference in the uptake between the caudate and the putamen. The glucose metabolism decreased in the cerebral cortices and the striatum: this finding was also different from those of Parkinson's disease. A normal 18F-dopa uptake with a markedly decreased striatal glucose metabolism was observed in cases of Huntington's disease. The 18F-dopa uptake increased and the glucose metabolism was normal in cases of idiopathic dystonia. Various patterns of 18F-dopa uptake and glucose metabolism were thus observed in the various disorders of basal ganglia. These results suggest that the measurements of the 18F-dopa uptake and glucose metabolism would be useful for evaluating the function of the basal ganglia in various disorders of basal ganglia.

Basal Ganglia↗

PubMed2001

Systematic review of proton magnetic resonance spectroscopy of the striatum in parkinsonian syndromes.

It has been suggested that proton magnetic resonance spectroscopy (MRS) of the striatum can differentiate between parkinsonian syndromes. The present study aims to examine this claim by performing a systematic review of the existing literature. A MEDLINE search was performed between 1966 and October 1999, along with searches of conference abstracts and reference lists of papers identified. Eleven groups have used MRS to examine metabolite ratios in the striatum in Parkinsonian syndromes. A number of these have shown reduced N-acetylaspartate/choline (NAA/Cho) and/or N-acetylaspartate/creatine (NAA/Cr) ratios in either idiopathic Parkinson's disease (IPD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP) or corticobasal degeneration. However, the heterogeneity in the results precludes the use of any of these findings in differential diagnosis at the present time. The only group to use absolute metabolite concentrations rather than ratios showed that the decreased NAA/Cho ratio in IPD was because of an increase in choline which is of uncertain biological significance. Further large multicentre trials are required using absolute quantitation of tissue metabolite concentrations and a standardized technique. The patients entering such studies must be rigorously assessed to establish the diagnosis of the type of parkinsonism as accurately as possible. Any discriminatory abnormality must be tested in a large prospective study of newly presenting parkinsonian patients with long-term clinical follow up and ultimate pathological confirmation of the diagnosis as far as possible.

Diagnosis, Differential↗

PubMed2003

Nigral glutathione deficiency is not specific for idiopathic Parkinson's disease.

The consistent findings of decreased levels of the major antioxidant glutathione in substantia nigra of patients with idiopathic Parkinson's disease (PD) has provided most of the basis for the oxidative stress hypothesis of the etiology of PD. To establish whether a nigral glutathione deficiency is unique to PD, as is generally assumed, or is present in other Parkinsonian conditions associated with nigral damage, we compared levels of reduced glutathione (GSH) in postmortem brain of patients with PD to those with progressive supranuclear palsy (PSP) and multiple system atrophy (MSA). As compared with the controls, nigral GSH levels were decreased in the PD and PSP patient groups (P < 0.05 for PD [-30%], PSP [-21%]), whereas a similar decrease in the MSA patient group did not reach statistical significance (P = 0.078, MSA [-20%]). GSH levels were normal in all examined normal and degenerating extra-nigral brain areas in PSP and MSA. A trend for decreased levels of uric acid (antioxidant and product of purine catabolism) also was observed in nigra of all patient groups (-19 to -30%). These data suggest that glutathione depletion, possibly consequent to overutilisation in oxidative stress reactions, could play a causal role in nigral degeneration in all nigrostriatal dopamine deficiency disorders, and that antioxidant therapeutic approaches should not be restricted to PD.

Aged↗

PubMed2002

Alpha-synuclein pathology affecting Bergmann glia of the cerebellum in patients with alpha-synucleinopathies.

We carried out immunohistochemical examinations of the brains (cerebella) of patients who had suffered from Parkinson's disease (PD), diffuse Lewy body disease (DLBD) or multiple system atrophy (MSA), using antibodies specific for alpha-synuclein. Alpha-synuclein-positive doughnut-shaped structures were found occasionally in the cerebellar molecular layer in some of these patients. Double-labeling immunofluorescence and immunoelectron microscopy studies revealed that these alpha-synuclein-positive doughnut-shaped structures were located in the glial fibrillary acidic protein-positive radial processes of Bergmann glia, corresponding to the outer area of Lewy body-like inclusions, and consisted of granulo-filamentous structures. These findings indicate that, although not frequently, Bergmann glia of the cerebellum are also the targets of alpha-synuclein pathology in alpha-synucleinopathies such as PD, DLBD and MSA.

Aged↗

PubMedDate not supplied

[Parkinsonian syndromes in Medellin (Colombia)].

INTRODUCTION: The definition of parkinsonian syndromes is based on clinical criteria. OBJECTIVE: To determine the frequency and management of parkinsonism, using criteria of inclusion and exclusion. PATIENTS AND METHODS: We selected 302 consecutive patients, 147 females and 155 males, with parkinsonism, age 66.8 (11.4) (range: 13-90), grades of education 7.5 (4.3) (range: 0-20). A structured and quantitative protocol was applied to the sample. RESULTS: The most frequent parkinsonian syndrome was the defined idiopathic Parkinson's disease with 132 participants (43.7%). Probably idiopathic Parkinson's disease was found in 60 cases (19.9%), and possible idiopathic Parkinson's disease in eight cases (2.6%); early onset Parkinson's disease in 10 cases (3.3%), juvenile Parkinson's disease in one case (0.3%), familial Parkinson's disease in five cases (1.7%); cortical Lewy body disease in 16 cases (5.4%), progressive supranuclear palsy in nine cases (3.3%), multiple systemic atrophy in eight cases (2.6%). Secondary Parkinson's disease was distributed as follow: vascular disease in 24 cases (8%), local lesion in 11 cases (3%), medications in 16 cases (5.3%), meningoencephalitis in one case (0.3%) and syphilis in one case (0.3%). Without medication was found 1.5% of sample, which was in Hoehn & Yarh's state I to II. In monotherapy was found 23.2%, with two medications 46.7%, with three 23.5% and with four drugs 5.1%. Levodopa was prescript to 70.9%, anticholinergic to 51.3%, MAO-B-I to 33.4%, amantadine to 33.1%, D2 stimulants to 18.5%, and COMT-I to 2.6%. CONCLUSION: Structured protocol for assessment of parkinsonian syndromes allows reliable diagnoses for clinical and epidemiological purposes.

Adolescent↗

PubMed2000

Ubiquitin-immunoreactive skein-like inclusions in the neostriatum are not restricted to amyotrophic lateral sclerosis, but are rather aging-related structures.

We examined the presence of ubiquitin-immunoreactive skein-like inclusions (SLI) in the neostriatum and spinal cord in normal individuals and patients with different neurodegenerative diseases. Ubiquitin-immunoreactive SLI in the neostriatum were observed both in the normal individuals and in the patients with a variety of neurodegenerative diseases. In particular, SLI were frequently seen in normal aged subjects and certain neurodegenerative diseases, such as progressive supranuclear palsy and myotonic dystrophy. In contrast, the occurrence rate of SLI in cases with Pick's disease and multiple system atrophy tended to decrease. On the other hand, SLI in the spinal anterior horn were detected in cases of amyotrophic lateral sclerosis, but not in any cases with other neurodegenerative diseases. SLI in the neostriatum were also identifiable using phosphotungstic acid-hematoxylin and Gomori trichrome staining. Ubiquitin immunoelectron microscopy demonstrated that the SLI in the neostriatum corresponded to bundles of filaments. These features of SLI in the neostriatum were quite similar to those of intracytoplasmic rod-like inclusions (RLI) in the large neurons of caudate nucleus, which were first described by Kojima and Ogawa in 1974. Our findings indicate that SLI in the neostriatum are ubiquitin-related structures whose occurrence increases by aging, and less frequently accompany several neurodegenerative diseases, and are identical to at least some RLI.

Aging↗

PubMed2003

Routine MRI for the differential diagnosis of Parkinson's disease, MSA, PSP, and CBD.

We assessed the usefulness of routine MRI for the differential diagnosis of Parkinson's disease (PD) with "atypical" parkinsonian syndromes in everyday clinical practice. We studied routinely performed MRI in PD (n = 32), multiple system atrophy (MSA, n = 28), progressive supranuclear palsy (PSP, n = 30), and corticobasal degeneration (CBD, n = 26). From a preliminary analysis of 26 items, 4 independent investigators rated 11 easily recognizable MRI pointers organized as a simple scoring system. The frequency, severity and inter-rater agreement were determined. The total severity score was subdivided into "cortical", "putaminal", "midbrain", and "pontocerebellar" scores. The frequency of putaminal involvement (100%) and vermian cerebellar atrophy (45%) was significantly higher in MSA, but that of cortical atrophy (50%), midbrain atrophy and 3(rd) ventricle enlargement (75%) was higher in PSP and CBD. The median total score fairly differentiated "atypical" parkinsonian syndromes from PD (positive predictive value-PPV-90%). However, the median total score was unable to differentiate atypical parkinsonian syndromes each other. The "cortical" score distinguished CBD and PSP from MSA with a fair PPV (>90%). The PPV of the "putaminal" score was high (70%) for the differential diagnosis of MSA with PSP and CBD. The "midbrain" score was significantly higher in PSP and CBD compared to MSA. These results are in accordance with the underlying pathology found in these disorders and demonstrate that a simple MRI scoring procedure may help the neurologist to differentiate primary causes of parkinsonism in everyday practice.

Brain↗