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At least 19 recordsLinked to original sources
PubMed1992

[High-field-strength magnetic resonance imaging and SPECT of multiple system atrophy].

Two cases of multiple system atrophy (MSA) showing similar abnormalities by magnetic resonance (MR) imaging and SPECT are reported. The clinical diagnoses of the two cases were striatonigral degeneration (SND) and sporadic olivopontocerebellar atrophy (OPCA). In addition, one case of sporadic OPCA without parkinsonism was used for comparison. The MR images were obtained using a 1.5-T MR system and included spin-echo transverse sections with T1-weighted images (TR = 450 ms and TE = 15 ms) and T2-weighted images (TR = 2500 ms and TE = 90 ms). The T1-weighted images demonstrated atrophy of cerebellum and pons, with increased signal intensity in the bilateral putamen. The T2-weighted images demonstrated decreased signal intensity in the putamen, as reported recently. SPECT demonstrated reduced uptake in the celleberum, basal ganglia and frontal lobe cortex. The putaminal changes evident on T1-weighted images may have resulted from deposition of pigments such as neuromelanin and lipofuscin, related to parkinsonism. Both T1- and T2-weighted MRI seem to be useful clinical diagnosis of MSA.

Brain↗
PubMed1992

Accumulation of tubular structures in oligodendroglial and neuronal cells as the basic alteration in multiple system atrophy.

In 8 brains of patients with various combinations of striatonigral degeneration, olivopontocerebellar atrophy and Shy-Drager syndrome, inclusion bodies were demonstrated in the cytoplasm and nucleus of both neuronal and oligodendroglial cells and in neuronal processes by means of silver staining, immunocytochemistry and electron microscopy. Differing from oligodendroglial cytoplasmic inclusions recognized by anti-ubiquitin, anti-alpha- and anti-beta-tubulin, and anti-tau antibodies, neuronal cytoplasmic inclusions were stained only by anti-ubiquitin antibody but not with those raised against cytoskeletal proteins. Tubular structures forming the inclusion bodies irrespective of their glial or neuronal location, have fuzzy cover and side extensions which make them similar to the linear structures described in motor neuron diseases. Our study proves that the accumulation of abnormal tubular structures in both oligodendrocytes and neurons is the basic pathological alteration in multiple system atrophy and defines multiple system atrophy as a group of diseases with similar cellular pathology or as a nosological entity.

Atrophy↗
PubMed1992

Altered vasopressin response to metoclopramide in multiple system atrophy: evidence of a cholinergic defect in the hypothalamus.

Multiple system atrophy (MSA) is a heterogeneous group of central neurological degenerations often associated with diffuse deterioration of the hypothalamic cholinergic neurons. In the hypothesis of an altered cholinergic regulation of vasopressin release, we evaluated vasopressin response to metoclopramide (20 mg i.v.), a cholinomimetic agonist, in 12 MSA patients. In the same patients the hemodynamic and osmolal control of vasopressin was also evaluated. We found that MSA patients had significantly lower basal plasma vasopressin values and higher plasma osmolality than control subjects. However, they displayed a normal vasopressin response to osmotic stimulation. During head-up tilting, orthostatic hypotension occurred in all patients, and the vasopressin response to hypotension was severely blunted in 5 of 12 patients, thus demonstrating the presence of a lesion of the afferent noradrenergic pathways. Metoclopramide increased vasopressin in control subjects, whereas MSA patients did not display any increase in vasopressin. These results clearly indicate that cholinergic neurons that regulate vasopressin release are damaged in MSA. Such an alteration may be dissociated from the lesion of the afferent noradrenergic pathways. As a consequence of the altered vasopressin release, MSA patients show lower plasma vasopressin levels with consequent propensity to dehydration and hypovolemia, which may further aggravate their hypotension.

Autonomic Nervous System Diseases↗
PubMed1992

Immunocytochemical and ultrastructural studies of neuronal and oligodendroglial cytoplasmic inclusions in multiple system atrophy. 2. Oligodendroglial cytoplasmic inclusions.

Oligodendroglial cytoplasmic inclusions (OCI) in multiple system atrophy were investigated immunocytochemically and ultrastructurally. Among the 17 cases examined, 16 had OCIs. Almost all OCIs were positive for both alpha B-crystallin and ubiquitin. The antibodies against tubulin, paired helical filament and tau stained OCIs to various extents. Ultrastructurally OCIs consisted of meshworks of granule-associated filaments about 25 nm in diameter that sometimes formed flame-shaped tangle-like structures. Immunoelectron microscopy showed that an epitope of alpha B-crystallin was located on the granule-associated filaments composing OCIs. Our studies further support a cooperative role of alpha B-crystallin, ubiquitin and cytoskeletal protein in the formation of some types of intracytoplasmic inclusions.

Adolescent↗
PubMed1992

Immunocytochemical and ultrastructural studies of neuronal and oligodendroglial cytoplasmic inclusions in multiple system atrophy. 1. Neuronal cytoplasmic inclusions.

Neuronal alterations in five cases of multiple system atrophy (MSA) were investigated histologically, immunocytochemically and ultrastructurally. Argentophilic neuronal cytoplasmic inclusions (NCIs) were observed in all cases. They were distributed, in order of decreasing frequency, in the pontine nucleus, striatum, subiculum, amygdala, hippocampus, dentate fascia, substantia nigra and inferior olivary nucleus. Anti-ubiquitin antibodies visualized many thickened neurites in the degenerating gray matter as well as NCIs. Some NCIs were also recognized by anti-phosphorylated neurofilament antibodies. Ultrastructurally, NCIs consisted of a meshwork of granule-associated filaments, the diameter ranging from 18 to 28 nm, that were mixed with neurofilaments. The granule-associated filaments were also present in the axoplasm of myelinated fibers. Our studies demonstrate widespread distribution of NCIs in the central nervous system of MSA. The same pathological process that forms the granule-associated filaments in axons may also be responsible for the formation of ubiquitin-positive thickened neurites. These axonal alterations, as well as neuronal perikaryal changes, may play an important role in the impaired neuronal function in MSA.

Adult↗
PubMed1992

[Loss of catecholaminergic neuron in the hypothalamus of multiple system atrophy].

Autonomic failure is one of the primary clinical features of multiple system atrophy (MSA); while the hypothalamus is thought to be a higher center regulating the autonomic nervous system. In the hypothalamus, catecholamine depletion had been confirmed by neurochemical studies but no marked changes had yet been demonstrated by pathological studies. Using three MSA and three control cases, we evaluated the quantitative changes of catecholamine (CA)-containing neurons in the hypothalamus. As markers of CA neurons, neuromelanin (NM)- and tyrosin hydroxylase (TH)-containing neurons were stained by Fontana-Masson and the immunohistochemical technique alternatively. Serial coronal sections, 10 microns thick, were evaluated every tenth section for NM neurons, while two sections were evaluated for TH neurons. The distributions of NM and TH neurons were almost identical; most of them were clustered in the periventricular and arcuate nuclei. The mean numbers of NM and TH neurons per slice were significantly lower in MSAs than in the controls (T test, p less than 0.01); the former were 21.0, 31.6, and 13.7 in MSAs and 78.4, 54.1, and 84.3 in the controls, while the latter were 1.5, 15.5, and 20.5 in MSAs and 48.0, 62.0, and 50.5 in the controls. The clinico-pathological correlation was suggested by the significant differences in the number of TH neurons between two MSA cases: a case with severe orthostatic hypotension and a case with a milder one. The ratio of TH and NM neurons, as obtained from the adjusted sections, was constant in all MSA cases, and there was a positive statistical correlation, but it altered in each control case.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed2025

Distinct spatial transcriptomic patterns of substantia Nigra in Parkinson disease and Parkinsonian subtype of multiple system atrophy.

To investigate transcriptomic signatures of Parkinson's disease (PD) and the Parkinsonian subtype of Multiple System Atrophy (MSA-P) in substantia nigra pars compacta (SNpc), we conducted transcriptome analysis using in-situ hybridization on paraffin-embedded SNpc tissues from post-mortem brains. The study included 2 MSA-P patients, 2 PD patients, and 2 healthy controls (HC), with 12 regions of interest (ROIs) selected from the dorsal to ventral and medial to lateral aspects of the SNpc. A total of 72 ROIs from 6 participants were analyzed, and differentially expressed genes (DEGs) were identified by comparing MSA-P, PD and HC groups. The MSA-P group showed 88 upregulated DEGs and 326 downregulated DEGs (adjusted &#x1d45d;<0.05) compared to HC. The downregulated DEGs were significantly enriched in pathways related to ribosomal translation, immune processes, mitochondrial function, and autophagy. Notably, the dorsomedial quadrant was uniquely linked to antigen presentation, while other quadrants showed downregulation of protein synthesis. The PD group exhibited 165 upregulated DEGs and 350 downregulated DEGs (adjusted &#x1d45d;<0.05) compared to HC, with downregulated DEGs associated with ribosomal translation, mitochondrial function, and the ubiquitin-proteasome system. In both MSA-P and PD, the upregulated DEGs were not associated with any pathways or biological process in gene enrichment analysis. In network propagation analysis, amyloid precursor protein was the most significant network hub among DEGs in both MSA-P and PD. Comparing the transcriptomic signatures of SNpc between MSA-P and PD, we found immune/inflammation, mitochondrial function and neural signaling related genes were significantly downregulated in MSA-P compared to PD. Overall, the transcriptomic signature of the SNpc in MSA-P and PD revealed overlapping but distinct features, including alterations in protein synthesis, immune processes, mitochondrial function, and protein degradation systems. Future studies with larger cohorts and functional validation are needed to further elucidate these findings.

Humans↗
PubMed2026

Plasma cfDNA hypermethylation at SNCA intron 1 as a potential blood-based epigenetic signal in Parkinson's disease and multiple system atrophy.

BACKGROUND: The accumulation of &#x3b1;-synuclein (SNCA) in the central nervous system is a hallmark of Parkinson's disease (PD) and multiple system atrophy (MSA). SNCA intron 1 methylation is implicated in SNCA transcriptional regulation and may serve as a peripheral epigenetic signal in synucleinopathies. However, studies of SNCA methylation in leukocyte-derived DNA have yielded inconsistent results. We aimed to evaluate whether cell-free DNA (cfDNA)-based SNCA intron 1 methylation differs in PD or MSA compared with normal controls (NC). METHODS: Plasma cfDNA was collected from 105 patients with PD, 50 with MSA, and 114 NC. DNA methylation at CpG sites 10-17 was quantified by bisulfite pyrosequencing. Multivariable linear and logistic regression models, adjusted for age, sex, and education, were used to compare methylation levels and estimate odds ratios (ORs). RESULTS: Patients with PD exhibited hypermethylation at CpG site 14 and higher mean methylation across CpG sites 10-17 compared with NC. Patients with MSA showed hypermethylation at CpG sites 10, 12, 13, and 17 and elevated mean methylation. Elevated mean methylation was also observed in drug-na&#xef;ve de novo PD and early-stage PD patients. Compared with the lowest tertile, the highest mean methylation tertile was associated with increased odds of PD (OR, 2.49; 95% CI, 1.08-5.92) and MSA (OR, 5.02; 95% CI, 1.58-18.00). CONCLUSION: Plasma cfDNA SNCA intron 1 hypermethylation is associated with PD and MSA and detectable in drug-na&#xef;ve and early-stage PD. It may represent a peripheral epigenetic alteration and warrants evaluation as an adjunctive signal for early screening.

Humans↗
PubMed1976

[Multiple systemic atrophies, mental retardation, neurogenic amyotrophy and congenital bone fragility. A new neuro-generative disorder].

Five cases of a congenital neurological disorder are reported. Four patients, born after a breech delivery, belong to one sibship while the fifth patient is the only child in another family. The clinical features include quadriplegia, amyotrophy, a peripheral neuropathy, severe mental retardation and a subluxation of the hips. X-rays reveal diffuse osteoporosis and multiple spontaneous fractures. Autopsies in 3 patients showed multiple system atrophies involving the spinal cord and the cerebellum, coarse cerebral gyri and a marked reduction in volume of the white matter. These various pathological features are compared with the lesions found in a few other cases reported in the literature, none of which can be considered to be identical to the ones described. It is therefore felt that the condition under discussion represents a new syndrome to be classified, at least temporarily, within the group of multiple system atrophies.

Atrophy↗
PubMed1992

Argyrophilic glial intracytoplasmic inclusions in multiple system atrophy: immunocytochemical and ultrastructural study.

Argyrophilic intracytoplasmic inclusions in oligodendrocytes (AGCIs) were seen in all of 15 cases of multiple system atrophy (MSA), and none in other neurodegenerative diseases, including 9 cases of Menzel-type olivopontocerebellar atrophy and 4 cases of Joseph's disease. The inclusions were widespread, not only in the olivopontocerebellar and striatonigral systems but also among fibers connecting their affecting lesions of MSA. Immunohistochemically, they were closely associated with tau, tubulins and microtubule-associated protein 5. Ultrastructurally, they consisted of 30- to 50-nm filaments (not tubules) and electron-dense granules, in varying proportions, and their formation is discussed. The specific occurrence of AGCIs could be a key to approach the pathogenesis of MSA.

Atrophy↗
PubMed2026

Chromosome X-wide association study in multiple system atrophy identifies sex-differential risk loci.

The human X chromosome accounts for &#x223c;5% of the genome. Despite its size, the role of X-chromosomal variants in human diseases is not well understood, mainly due to its distinct inheritance pattern and the frequent omission of sex chromosomes from genome-wide association studies. This study used whole-genome sequencing data from 888 multiple system atrophy (MSA) cases and 7128 controls to perform an X-chromosome-wide common variant association study. Our analyses revealed two sex-differential risk loci: one located at Xq28, associated with increased risk for MSA in females [index variant: rs4898389, odds ratio (OR) = 1.69, 95% confidence interval (CI) = 1.40-2.03, P-value = 2.43 &#xd7; 10&#x207b;&#x2078;], and another at Xp22.2 within the TBL1X gene, identified in males (index variant: rs6638956, OR = 1.48, 95%CI = 1.26-1.73, P-value = 9.92 &#xd7; 10&#x207b;&#x2077;). In the Xq28 locus, colocalization analyses pointed to FAM3A and PLXNA3 as genes of interest. These findings emphasize the vital role of sex-differential genetic factors in the pathogenesis of MSA.

Humans↗
PubMed1979

Multiple system atrophy with autonomic failure: clinical, histological and neurochemical observations on four cases.

Four cases of progressive autonomic failure are described, in all of which there were additional non-autonomic neurological abnormalities, including pyramidal, extra-pyramidal and cerebellar features. Histological examination revealed cell degeneration in the substantia nigra, putamen and intermediolateral columns of the spinal cord as a common pathological finding. In addition, 3 cases showed loss of Purkinje cells in the cerebellum and degeneration of pontine nuclei and inferior olivary nuclei. In one case there was cell loss from the locus coeruleus, caudate nucleus, vestibular nuclei and dorsal vagal nuclei. These were, therefore, cases of multiple system atrophy. Neurochemically, a common feature was a profound depletion in dopamine and noradrenaline from brain regions which are normally rich in these catecholamines. Central cholinergic systems appeared to be involved also, but to a variable degree.

Aged↗
PubMed1992

Cerebrospinal fluid norepinephrine, 3-methoxy-4-hydroxyphenylglycol and neuropeptide Y levels in Parkinson's disease, multiple system atrophy and dementia of the Alzheimer type.

Neuropeptide Y, one of the most abundant polypeptides within the nervous system, is co-stored with catecholamines, especially norepinephrine (NE), thus suggesting its possible involvement in pathologies characterized by a noradrenergic impairment. In Parkinson's disease (PD), as well as in multiple system atrophy (MSA), a central noradrenergic deficit has been demonstrated, and in the dementia of Alzheimer type (DAT) an impaired noradrenergic transmission has been postulated. In this study we determined CSF NE and MHPG levels in 29 PD, 15 MSA, 22 DAT patients and in 36 controls, while CSF NPY-immunoreactivity (NPY-ir) levels were measured in 10 PD, 7 MSA, 10 DAT patients and 20 controls. PD, MSA, and DAT patients showed a significant reduction in CSF NPY-ir and NE levels compared with controls, while CSF MHPG levels resulted in a reduction in only the MSA group. Furthermore, an inverse correlation between either NE or MHPG levels and the duration of the orthostatic hypotension was found in MSA patients while for DAT patients the MHPG levels were directly correlated to the severity of cognitive impairment, and inversely to the duration of illness.

Adult↗
PubMed1992

[Multiple system atrophy with macro square wave jerks and pendular nystagmus].

A 51-year-old woman was admitted to our hospital because of gait disturbance and dysuria. Neurological examination revealed limb and truncal ataxia, orthostatic hypotension, cogwheel rigidity in all limbs, generalized hyperreflexia without pathological reflex, and horizontal gaze nystagmus. She became progressively worse and bedridden at age 52. Then she developed abnormal eye movements. Electrooculogram revealed vertical, horizontal or oblique macro square wave jerks and pendular nystagmus. Macro square wave jerks appeared during fixation and disappeared with eye closure or in the dark room. Macro square wave jerks were characterized by a duration of about 200 msec and an amplitude of 10 to 15 degrees. Pendular nystagmus with a duration of several seconds and amplitude of 5 to 15 degrees appeared when she changed her fixation or the point of fixation disappeared. Macro square wave jerks and pendular nystagmus were mildly suppressed after the intramuscular injection of 100 mg of phenobarbital, the oral intake of sodium valproate of 600 mg/day or baclofen of 60 mg/day. They were almost completely depressed after the intravenous injection of 3 mg of diazepam or the oral intake of clonazepam of 1.5 mg/day. We suggested that both macro square wave jerks and pendular nystagmus in this patient might be caused by the dysfunction of GABAergic system in the saccadic eye movement system.

Atrophy↗
PubMed1992

[Oligodendroglial inclusions, a marker of multisystemic atrophies].

Nine cases of multiple system atrophy and 1 case of autosomal dominant olivopontocerebellar atrophy (neuropathological diagnosis) were retrospectively examined for the presence of oligodendroglial inclusions. Clinical diagnosis in the first 9 cases had been: olivopontocerebellar atrophy (3 cases), atypical Parkinson's disease (2 cases), Shy-Drager syndrome (2 cases) and multiple system atrophy (1 case); one of the patients could not be included in any of the above mentioned groups. The oligodendroglial inclusions were argyrophilic and located in the cytoplasm around the nucleus. They were revealed by Bodian's method in all cases of multiple system atrophy. They were not found in the case of autosomal dominant olivopontocerebellar atrophy. They were labelled by anti-ubiquitin antibodies, and were negative with anti-tau antibodies. At electron microscopy, they consisted of rectilinear profiles coated with a fuzzy material (diameter: 20-33 nm); this aspect was compatible with microtubules. Oligodendroglial inclusions were prominent in regions selectively vulnerable in multiple system atrophy (tegmentum pontis, putamen, inferior olives, substantia nigra and cerebellar white matter), even in those areas where neuronal loss or fascicular atrophy were minimal or absent. They were also observed in regions considered to be spared in multiple system atrophy, such as the motor cortex and the corpus callosum. Argyrophilic oligodendroglial inclusions are an early and specific marker of multiple system atrophy. It is suggested that autosomal dominant olivopontocerebellar atrophy lacking oligodendroglial inclusions does not belong to multiple system atrophy.

Adult↗
PubMed1992

Differential responses in superior mesenteric artery blood flow may explain the variant pressor responses to clonidine in two groups with sympathetic denervation.

1. Measurement of superior mesenteric artery blood flow along with systemic and regional haemodynamic changes in blood pressure, heart rate, cardiac index, forearm blood flow, digital skin blood flow and index finger temperature were made before and after administration of clonidine (2 micrograms/kg body weight intravenously) in 10 patients with multiple-system atrophy, 10 patients with pure autonomic failure and 15 age-matched healthy control subjects. 2. After clonidine, blood pressure fell in patients with multiple-system atrophy and control subjects but not in patients with pure autonomic failure. 3. Resting superior mesenteric artery blood flow was similar in patients with multiple-system atrophy and control subjects, but was higher in patients with pure autonomic failure. The fall in blood pressure after clonidine was accompanied by active dilatation of the superior mesenteric artery in patients with multiple-system atrophy and control subjects. This did not occur in patients with pure autonomic failure. 4. After clonidine, there was a fall in cardiac index in patients with multiple-system atrophy. 5. After clonidine, changes in other haemodynamic parameters were not significant in any group, except for a fall in forearm blood flow and a rise in index finger temperature in control subjects. 6. We conclude that after clonidine there are differential superior mesenteric artery blood flow responses in the two groups with autonomic failure (multiple-system atrophy and pure autonomic failure). These may relate to differences in the site of the sympathetic lesion, which is considered to be mainly central in multiple-system atrophy but peripheral in pure autonomic failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

[The clinical and computed tomographic criteria of the diagnosis of multiple systemic cerebral atrophy with progressive autonomic insufficiency (the Shy-Drager syndrome)].

Based on clinical and CT examination of 3 patients with Shy-Drager syndrome and the reported data, differential diagnosis of the given diseases is under discussion. Shy-Drager syndrome is characterized by CT signs of progressive atrophy of the pons and cerebellum with no essential changes in the supratentorial brain structures. The authors support a proposal to use the term "multiple systemic atrophy" for designation of the disease entity that includes both Shy-Drager syndrome and sporadic patterns of olivopontocerebellar and strionigral degenerations in which the disease debuts by motor disorders of the extrapyramidal and cerebellar nature rather than by vegetative disturbances.

Brain↗