Changes In Multiple System Atrophy Research Articles

Intraocular pressure and choroidal thickness postural changes in multiple system atrophy and Parkinson\u2019s disease

To evaluate intraocular pressure (IOP) and choroidal thickness (ChT) postural changes in multiple system atrophy (MSA), Parkinson’s disease (PD) patients and healthy controls (HC). 20 MSA patients, 21 PD patients and 14 HC, were examined. All subjects underwent a complete examination, including corneal thickness, ChT, IOP and axial length (AL) measurements. IOP measurement was performed in supine, sitting, and standing positions, whereas ChT in sitting and standing positions. Supine to standing IOP variations were significantly higher in MSA vs PD(p = 0.01) and in MSA vs HC (p < 0.0001), whereas no significant differences were observed between PD and HC (p = 0.397). Mean sub-foveal ChT in MSA was 240 ± 92 μm in sitting position, and 215 ± 94 μm in standing position with a significant reduction (p = 0.008). Mean sub-foveal ChT in PD was 258 ± 79 μm in sitting position, and 259 ± 76 μm in standing position (p = 0.887). In HC it was 244 ± 36 μm in sitting position, and 256 ± 37 μm in standing position with a significant increase (p = 0.007). The significant IOP and ChT postural changes can be considered additional hallmarks of autonomic dysfunction in MSA and further studies are needed to consider them as biomarkers in the differential diagnosis with PD.

Fixel-Based Analysis of White Matter Degeneration in Patients With Progressive Supranuclear Palsy or Multiple System Atrophy, as Compared to Parkinson's Disease.

Introduction: White matter degeneration may contribute to clinical symptoms of parkinsonism.Objective: We used fixel-based analysis (FBA) to compare the extent and patterns of white matter degeneration in different parkinsonian syndromes—including idiopathic Parkinson's disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP).Methods: This is a retrospective interpretation of prospectively acquired data of patients recruited in previous studies during 2008 and 2019. Diffusion-weighted images were acquired on a 3-Tesla scanner (diffusion weighting b = 1000 s/mm2–applied along either 64 or 30 non-collinear directions) from 53 patients with PD (men/women: 29/24; mean age: 65.06 ± 5.51 years), 47 with MSA (men/women: 20/27; mean age: 63.00 ± 7.19 years), and 50 with PSP men/women: 20/30; mean age: 65.96 ± 3.14 years). Non-parametric permutation tests were used to detect intergroup differences in fixel-related indices—including fiber density, fiber cross-section, and their combination.Results: Patterns of white matter degeneration were significantly different between PD and atypical parkinsonisms (MSA and PSP). Compared with patients with PD, those with MSA and PSP showed a more extensive white matter involvement—noticeably descending tracts from primary motor cortex to corona radiata and cerebral peduncle. Lesions of corpus callosum were specific to PSP and absent in both MSA and PD.Discussion: FBA identified specific patterns of white matter changes in MSA and PSP patients compared to PD. Our results proved the utility of FBA in evaluation of implied biological processes of white matter changes in parkinsonism. Our study set the stage for future applications of this technique in patients with parkinsonian syndromes.

Identification of plasma microRNA expression changes in multiple system atrophy and Parkinson\u2019s disease

MicroRNAs (miRNAs) are endogenous small (18–25 nt), single-stranded, non-coding RNAs that play key roles in post-transcriptional gene expression regulation. The expression profiles of miRNAs in biofluids and tissues change in various diseases. Multiple system atrophy (MSA) and Parkinson’s disease (PD) are both categorized as α-synucleinopathies and often present with similar clinical manifestations. This study aimed to identify miRNAs that are differently expressed in plasma samples of PD patients, MSA patients, and healthy controls. We used microarray analysis to screen for miRNAs that are up- and down-regulated in these patients and analyzed the relative-quantitative expression levels of the identified miRNAs by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Hsa-miR-671-5p, hsa-miR-19b-3p, and hsa-miR-24-3p showed significantly different expression levels among patients with MSA-C, MSA-P, or PD, and healthy controls. Hsa-miR-671-5p levels were lower in the MSA-P and PD than the MSA-C and control groups, hsa-miR-19b-3p levels were higher in the PD than the other groups, and hsa-miR-24-3p levels were higher in the PD than the MSA-C group. Hsa-miR-671-5p was the first miRNA shown to be expressed differently between MSA-C and MSA-P in plasma. Interestingly, the expression levels of hsa-miR-19b-3p and hsa-miR-24-3p were positively correlated, indicating that these miRNAs may be involved in the same processes in PD pathogenesis. Our findings suggest that hsa-miR-671-5p, hsa-miR-19b-3p, and hsa-miR-24-3p may reflect the pathophysiology or symptoms of PD and MSA.

Wide distribution of alpha-synuclein oligomers in multiple system atrophy brain detected by proximity ligation

Multiple system atrophy (MSA) is a fatal adult-onset neurodegenerative disease that is characterized by varying degrees of cerebellar dysfunction and Parkinsonism. The neuropathological hallmark of MSA is alpha-synuclein (AS)-positive glial cytoplasmic inclusions (GCIs). Although severe neuronal loss (NL) is also observed in MSA, neuronal inclusions (NIs) are rare compared to GCIs, such that the pathological mechanism of NL in MSA is unclear. GCIs and NIs are late-stage pathology features relative to AS oligomers and may not represent early pathological changes in MSA. To reveal the early pathology of MSA, it is necessary to examine the early aggregation of AS, i.e., AS oligomers. Here, we adopted a proximity ligation assay (PLA) to examine the distribution of AS oligomers in brain tissue samples from patients with MSA and other diseases. Surprisingly, MSA brains showed a widespread distribution and abundant accumulation of oligomeric AS in neurons as well as oligodendrocytes of the neocortex. In several regions, oligomeric AS signal intensity was higher in cases with MSA than in cases with Parkinson’s disease. In contrast to previous studies, AS–PLA revealed abundant AS oligomer accumulation in Purkinje cells in MSA brains, identifying oligomeric AS accumulation as a possible cause of Purkinje cell loss. This wide distribution of AS oligomers in MSA brain neurons has not been described previously and indicates a pathological mechanism of NL in MSA.

Cerebellar atrophy and its contribution to motor and cognitive performance in multiple system atrophy.

ObjectiveNeuroanatomical differences in the cerebellum are among the most consistent findings in multiple system atrophy (MSA) patients. This study performed a detailed cerebellar morphology in MSA patients and its two subtypes: MSA-P (parkinson's symptoms predominate) and MSA-C (cerebellar symptoms predominant), and their relations to profiles of motor and cognitive deficits.Materials and methodsStructure MRI data were acquired from 63 healthy controls and 61 MSA patients; voxel-based morphometry and the Spatially Unbiased Infratentorial Toolbox cerebellar atlas were performed to identify the cerebellar gray volume changes in MSA and its subtypes. Further, the gray matter changes were correlated with the clinical motor/cognitive scores.ResultsPatients with MSA exhibited widespread loss of cerebellar volume bilaterally, relative to healthy controls. In those with MSA-C, gray matter loss was detected from anterior (bilateral lobule IV-V) to posterior (bilateral crus I/II, bilateral lobule IX, left lobule VIII) cerebellar lobes. Lower anterior cerebellar volume negatively correlated with disease duration and motor performance, whereas posterior lobe integrity positively correlated with cognitive assessment. In patients with MSA-P, atrophy of anterior lobe (bilateral lobules IV-V) and posterior lobe in part (left lobule VI, bilateral IX) was evident; and in left cerebellar lobule IX, gray matter loss negatively correlated with motor scores. Direct comparison of MSA-P and MSA-C group outcomes showed divergence in right cerebellar crus II only.ConclusionsOur data suggest that volumetric abnormalities of cerebellum contribute substantially to motor and cognitive performance in patients with MSA. In patients with MSA-P and MSA-C, affected regions of cerebellum differed.

Stridor-related gray matter alterations in multiple system atrophy: A pilot study

IntroductionThe neuroanatomical substrate of stridor associated with Multiple System Atrophy (MSA) remains unclear. We evaluated stridor-related gray matter (GM) changes in MSA. Methods36 MSA patients underwent standardized nocturnal video-polysomnography and brain MRI. Differences in GM density between MSA patients with and without stridor and a sample of 22 matched healthy controls were evaluated with Voxel Based Morphometry protocol supplemented by a specific tool (SUIT) for analysing infratentorial structures. ResultsStridor was confirmed in 14 patients (10 MSA-cerebellar variant; 10 M; mean ± SD age = 61.6 ± 8.9years; disease duration = 5.2 ± 2.9years) and absent in 22 (11 MSA-cerebellar variant; 18 M; age = 61.4 ± 9.9years; disease duration = 4.8 ± 3.4years). Compared to MSA without stridor, patients with stridor showed higher GM density in the cerebellum (p < 0.05, corrected for the MSA-cerebellar variant and uncorrected when considering both MSA-variants) and lower in the striatum (p < 0.05, uncorrected). ConclusionsThis preliminary study has demonstrated for the first time in MSA stridor-related GM changes in striatal and cerebellar regions. Abnormalities in these regions were previously reported in dystonic disorders affecting laryngeal muscles, suggesting the hypothesis that stridor pathophysiology is dystonia-related. These results need however to be confirmed in a larger sample of patients.

Functional MRI of disease progression in Parkinson disease and atypical parkinsonian syndromes.

To explore longitudinal changes in brain activity in patients with Parkinson disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP) using task-based functional MRI (fMRI). A total of 112 individuals were scanned 1 year apart while performing a unimanual grip force task: 46 PD, 13 MSA, 19 PSP, and 34 healthy controls. The outcome measure was percent signal change in prespecified regions of interest: putamen, primary motor cortex (M1), supplementary motor area (SMA), and superior motor regions of the cerebellum (lobules V-VI). Patients with PD showed a decline in functional activity over the course of 1 year in the putamen and M1 compared to controls. Changes after 1 year in MSA were exclusively extrastriatal, and included a reduction in functional activity in M1, SMA, and superior cerebellum. In PSP, all regions of interest were less active at 1 year compared to baseline. The functional activity of these regions did not change in the control group. We provide evidence using task-based fMRI for cortical and striatal functional deterioration in PD over a 1-year period of time. Results also describe more widespread and unique patterns of functional changes in MSA and PSP compared to PD, suggesting distinct rates of disease progression in parkinsonian disorders that may assist in future clinical studies testing the potential efficacy of disease-modifying therapies.

Retinal thinning correlates with clinical severity in multiple system atrophy.

To analyze retinal thickness changes in multiple system atrophy (MSA) and correlate changes with disease severity and subtypes of MSA. A total of 36 MSA (27 MSA-P and 9 MSA-C) patients and 71 healthy control subjects underwent general ophthalmologic examination and optical coherence tomography (OCT) scans. Peripapillary retinal nerve fiber layer (RNFL) thickness and perifoveal retinal thickness were analyzed separately. The generalized estimating equation model was used with age as a covariate to adjust for within-patient inter-eye correlations and the effect of age on retinal or RNFL thickness. Correlation analysis between RNFL, perifoveal thickness, and clinical parameters, the Unified MSA Rating Scale (UMSARS) and Global Disability Score (GDS), was also done. MSA patients showed significantly decreased peripapillary RNFL thickness in the inferior (P=0.047) and inferotemporal (P=0.017) sectors and significant perifoveal thinning in the superior outer sector (P=0.042) compared to healthy controls. Both RNFL and perifoveal thinning were more marked and widespread in MSA-P than MSA-C patients. The UMSARS and GDS showed significant negative correlation with center and total macular perifoveal thickness and also the inferior and nasal outer sectors. Peripapillary RNFL and perifoveal retinal thinning were observed in MSA patients and retinal thinning correlated with the clinical severity of MSA. Structural changes in the retina may reflect the degree and pattern of neurodegeneration occurring in MSA.

Longitudinal Clinical and Brain MRI Changes in Multiple System Atrophy (P4.306)

Longitudinal Clinical and Brain MRI Changes in Multiple System Atrophy (P4.306)

Cognitive Impairment and Its Structural Correlates in the Parkinsonian Subtype of Multiple System Atrophy

Background/Aims: Previous studies indicate that patients with the parkinsonian subtype of multiple system atrophy (MSA-P) experience cognitive impairment. This study aimed to identify the existence of cognitive impairments and the different topographic patterns of morphological changes in MSA-P by means of imaging analysis, and also whether these morphological changes could be associated with cognitive dysfunctions in MSA-P. Methods: We recruited 15 nondemented probable MSA-P patients and 32 normal controls (NC) for neuropsychological testing and MRI. We analyzed morphological changes using cortical thickness analysis, voxel-based morphometry (VBM) and cerebellar volumetry. Multiple linear regression analysis was performed to evaluate the correlation of each cognitive score with the mean thickness of significant cortical-thinning clusters, mean gray-matter density of VBM clusters and cerebellar volume. Results: The scores on the Digit Span Test, the Seoul Verbal Learning Test (immediate and delayed), the phonemic Controlled Oral Word Association Test and the Stroop color test were significantly lower in the MSA-P group than in the NC group. We found two clusters exhibiting significant cortical thinning in the right paracentral lobule and parahippocampal gyrus. VBM analysis revealed significant gray-matter atrophy in the MSA-P group in the bilateral basal ganglia, cerebellum and temporal and frontal cortical areas. Multiple linear regression analysis demonstrated that cognitive dysfunction correlated significantly with thinning in the neocortex, cerebellum and striatum. Conclusions: Our data demonstrate that cortical and cerebellar atrophy and striatal degeneration are associated with cognitive impairment in patients with MSA-P.

Changes in total cell numbers of the basal ganglia in patients with multiple system atrophy — A stereological study

Total numbers of neurons, oligodendrocytes, astrocytes, and microglia in the basal ganglia and red nucleus were estimated in brains from 11 patients with multiple system atrophy (MSA) and 11 age- and gender-matched control subjects with unbiased stereological methods. Compared to the control subjects, the MSA patients had a substantially lower number of neurons in the substantia nigra (p=0.001), putamen (p=0.001), and globus pallidus (p<0.001), and, to a lesser extent in the caudate nucleus (p=0.03). A significantly lower number of oligodendrocytes were only observed in the putamen (p=0.04) and globus pallidus (p=0.01). In the MSA brains the total number of astrocytes was significantly higher in the putamen (p=0.04) and caudate nucleus (p=0.01). In all examined regions a higher number of microglia were found in the MSA brains with the greatest difference observed in the otherwise unaffected red nucleus (p=0.001). The results from the stereological study were supported by cell marker expression analyses showing increased markers for activated microglia. Our results suggest that microgliosis is a consistent and severe neuropathological feature of MSA, whereas no widespread and substantial loss of oligodendrocytes was observed. We have demonstrated significant neuronal loss in the substantia nigra, striatum, and globus pallidus of patients with MSA, while neurons in other basal ganglia nuclei were spared, supporting the region-specific patterns of neuropathological changes in MSA.

Imaging in multiple system atrophy

AbstractThe diagnosis of multiple system atrophy and its differentiation from Parkinson's disease can be challenging, particularly in early disease. Both structural and functional imaging studies can be helpful for making the diagnosis, and could potentially be used to monitor disease progression. Magnetic resonance imaging can show distinctive patterns of atrophy and signal changes in multiple system atrophy, such as the “hot cross bun” and hyperintense putaminal rim signs, which are relatively specific, but have low sensitivity. Diffusivity might be particularly helpful in differentiating multiple system atrophy from Parkinson's disease, and appears to change over time, although the correlation with changes in motor dysfunction is uncertain. Diffusion weighted imaging changes in the middle cerebellar peduncle can also reliably separate multiple system atrophy from progressive supranuclear palsy. Volumetry detects characteristic patterns of atrophy. Alterations in spectroscopic patterns and abnormal iron deposition have also been reported. Positron emission tomography or single‐photon emission computed tomography measures of striatal dopamine innervation are abnormal in multiple system atrophy and Parkinson's disease; the addition of dopamine D2 receptor imaging (preserved in Parkinson's disease) can be helpful in differentiating the two. However, fluorodeoxyglucose positron emission tomography shows different characteristic metabolic networks in the two conditions that change with disease progression, and is probably more useful. Functional imaging can also be used to detect changes in cholinergic innervation in multiple system atrophy, and to study neuroinflammation. Imaging of cardiac sympathetic innervation can also differentiate between Parkinson's disease and multiple system atrophy, and might be underutilized for this purpose.

Deficits in episodic memory relate to reduced hippocampal volumes in very-low-birth-weight (VLBW) young adults

WCN 2013 No: 2302 Topic: 36 — Other Topic Deficits in episodic memory relate to reduced hippocampal volumes in very-low-birth-weight (VLBW) young adults G. Lohaugen, K.J. Bjuland, M. Martinussen, J. Skranes. Child Rehabilitation, Sorlandet Hospital, Arendal, Norway; Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology (NTNU), Trondheim, Norway Background and aims: The hippocampus is regarded as a core structure for learning and memory functions. Academic problems are commonly reported in VLBW (bw ≤ 1500 g) children and adolescents, and the aims of this hospital-based, long-term follow-up study were to perform a comprehensive memory assessment in VLBW young adults and investigate the relationship between hippocampal volume and episodic memory compared to age-matched term born controls. Methods: Forty-two non-disabled VLBW and 61 age-matched controls were examined at age 19 with the WAIS-III, Wechsler Memory Scale-III and cerebral MRI. An automated MRI technique (FreeSurfer ver. 5.1) at 1.5 Tesla for morphometric analysis of hippocampal volumes was applied. Results: The VLBW group was at a disadvantage compared to controls on tests assessing visual immediate/delayed memory and working memory. The VLBW group had similar relative left (mean 0.244 (SE 0.003) mm, p = 0.242) and smaller right (mean: 0.243 (SE 0.004) mm, p = 0.027) hippocampal volumes vs. controls (left 0.249 (SE 0.003) mm; right 0.253 (SE 0.003) mm). Significant correlations were found between left (r = 0.344, p = 0.030) and right (r = 0.038, p = 0.016) relative hippocampal volumes and visual immediate memory. Working memory function was associated with right hippocampal volume (r = 0.392, p = 0.015). Conclusion: We found that being born preterm with VLBW has longterm negative consequences regarding memory functions, persisting into young adulthood. The relative hippocampal volumes were reduced in VLBW young adults compared to term born controls. Positive correlations were found between hippocampal volume and immediate visual and working memory function in the VLBW group. doi:10.1016/j.jns.2013.07.2305 Abstract — WCN 2013 No: 2310 Topic: 36 — Other Topic Oculomotor changes in multiple system atrophy: Clinical, MRI and laboratory features in eight patients WCN 2013 No: 2310 Topic: 36 — Other Topic Oculomotor changes in multiple system atrophy: Clinical, MRI and laboratory features in eight patients G. Lucii, F. Rosini, P. Federighi, E. Pretegiani, F. Giannini, A. Federico, A. Rufa. Eye Tracking & Visual Application Lab EVALab, UOC Neurologia e Malattie Neurometaboliche Dipartimento di Medicina Chirurgia e Neuroscienze, Universita degli Studi di Siena, Siena, Italy; UOC Neurofisiologia Clinica Dipartimento diMedicina Chirurgia e Neuroscienze, Universita degli Studi di Siena, Siena, Italy; c UOC Neurologia e Malattie Neurometaboliche Dipartimento di Medicina Chirurgia e Neuroscienze, Universita degli Studi di Siena, Siena, Italy Background: Multiple system atrophy (MSA) is a progressive adultonset α-synucleinopathy characterized by dysautonomia associated with cerebellar symptoms (MSA-C) or parkinsonism (MSA-P). Ocular motor changes, including saccadic dysmetria, saccadic intrusions and nystagmus, have been reported. Objective: To determine the ocular motor changes in MSA that may differentiate these patients from other neurodegenerative diseases with overlapping clinical features. Methods: Eight patients, six MSA-C and two MSA-P, were recorded. Mean age was 60 ± 3; mean disease duration was 4.87 ± 1.45 years. Horizontal (±10°; ±18°) and vertical (up/down 8°) visually-guided saccades and antisaccades were tested and compared with EVAlab's normative data. Three minutes of steady fixation were performed. Saccadic parameters, antisaccade errors with relative corrections and fixation changes were evaluated. Results: All patients showed significant reduction of amplitude (6.73° ± 2.11° vs 8.3° ± 0.09°)(P value = 0.026), and accuracy (2.01 ± 1.44 vs 1.17 ± 0.49)(P value = 0.004) of downward saccades. Amplitude at 18° of horizontal eccentricity (15.44° ± 2.56° vs 18.3° ± 0.9°) (P value b 0.0001) and accuracy at 10° (2.37 ± 0,86 vs 0.88 ± 0.52) (P value b 0.001) and 18° (4.86 ± 2.21 vs 1.22 ± 0.09)(P value b 0.001) of horizontal saccades were also decreased. Direction error in antisaccade task was about 45% with a 96% of spontaneous fast correction. Steady fixation was interrupted by saccadic intrusions (square wave jerks subtype, average number of 12/min and mean amplitude of 1.52° ± 0.31°). Conclusions: Our findings substantiate peculiar changes of saccade dynamics in MSA. Downward saccades are more impaired than horizontal. Voluntary saccades and fixation are also impaired and lesser than in other similar neurodegenerative diseases. Oculomotor profile helps to differentiate MSA from other neurodegenerative diseases with overlapping clinical features. doi:10.1016/j.jns.2013.07.2306 Abstract — WCN 2013 No: 2272 Topic: 36 — Other Topic Serial magnetic resonance imaging of acute necrotizing myelitis WCN 2013 No: 2272 Topic: 36 — Other Topic Serial magnetic resonance imaging of acute necrotizing myelitis E. Papageorgiou, K. Psychogios, D. Tzanetakos, I. Markakis, I. Xydakis, G. Gekas. Neurology, ‘St. Panteleimon’ General State Hospital, Nikaia,

Oculomotor changes in multiple system atrophy: Clinical, MRI and laboratory features in eight patients

Oculomotor changes in multiple system atrophy: Clinical, MRI and laboratory features in eight patients

Oculomotor Changes in Multiple System Atrophy: Clinical, MRI and Laboratory Features in Seven Patients (P06.014)

Oculomotor Changes in Multiple System Atrophy: Clinical, MRI and Laboratory Features in Seven Patients (P06.014)

Visual event-related potential changes in multiple system atrophy: Delayed N2 latency in selective attention to a color task

Recent studies demonstrated an altered P3 component and prolonged reaction time during the visual discrimination tasks in multiple system atrophy (MSA). In MSA, however, little is known about the N2 component which is known to be closely related to the visual discrimination process. We therefore compared the N2 component as well as the N1 and P3 components in 17 MSA patients with these components in 10 normal controls, by using a visual selective attention task to color or to shape. While the P3 in MSA was significantly delayed in selective attention to shape, the N2 in MSA was significantly delayed in selective attention to color. N1 was normally preserved both in attention to color and in attention to shape. Our electrophysiological results indicate that the color discrimination process during selective attention is impaired in MSA.

Axonal -synuclein aggregates herald centripetal degeneration of cardiac sympathetic nerve in Parkinson's disease

Degeneration of the cardiac sympathetic nerve occurs in both Parkinson's disease (PD) and dementia with Lewy bodies and begins early in the disease progression of PD, accounting for reduced cardiac uptake of meta-iodobenzylguanidine even in the early stages of Lewy body disease (LBD). We previously demonstrated that degeneration of the distal axons of the cardiac sympathetic nerve precedes loss of their mother neurons in the paravertebral sympathetic ganglia, suggesting distal dominant degeneration of the cardiac sympathetic nerve in PD. Because alpha-synuclein is one of the key molecules in the pathogenesis of this disease, we further investigated how alpha-synuclein aggregates are involved in this distal-dominant degeneration. Both cardiac tissues and paravertebral sympathetic ganglia were obtained for comparison from 20 patients with incidental Lewy body disease (ILBD), 10 with PD, 20 with multiple system atrophy (MSA) and 10 control subjects. Immunohistochemical analysis was performed using antibodies against tyrosine hydroxylase (TH) as a marker for sympathetic nerves, phosphorylated neurofilament as a marker for axons and phosphorylated alpha-synuclein for pathological deposits. We found that (i) alpha-synuclein aggregates in the epicardial nerve fascicles, namely the distal axons of the cardiac sympathetic nerve, were much more abundant in ILBD with preserved TH-ir axons than in this disease with decreased TH-ir axons and PD; (ii) alpha-synuclein aggregates in the epicardial nerve fascicles were closely related to the disappearance of TH-ir axons; (iii) in ILBD with preserved TH-ir axons, alpha-synuclein aggregates were consistently more abundant in the epicardial nerve fascicles than in the paravertebral sympathetic ganglia; (iv) this distal-dominant accumulation of alpha-synuclein aggregates was reversed in ILBD with decreased TH-ir axons and PD, which both showed fewer of these axons but more abundant alpha-synuclein aggregates in the paravertebral sympathetic ganglia and (v) MSA was completely different from ILBD and PD based on the preservation of TH-ir axons and the scarcity of alpha-synuclein aggregates in either the cardiac tissues or the paravertebral sympathetic ganglia. These findings indicate that accumulation of alpha-synuclein aggregates in the distal axons of the cardiac sympathetic nervous system precedes that of neuronal somata or neurites in the paravertebral sympathetic ganglia and that heralds centripetal degeneration of the cardiac sympathetic nerve in PD, which sharply contrasts with slight changes in MSA. This chronological and dynamic relationship between alpha-synuclein aggregates and distal-dominant degeneration of the cardiac sympathetic nervous system may represent the pathological mechanism underlying a common degenerative process in PD.

Usefulness of combined fractional anisotropy and apparent diffusion coefficient values for detection of involvement in multiple system atrophy

Objective: To determine whether apparent diffusion coefficient (ADC) values and fractional anisotropy (FA) values can detect early pathological involvement in multiple system atrophy (MSA), and be used to differentiate MSA-P...

Transcriptional changes in multiple system atrophy and Parkinson's disease putamen

Multiple system atrophy (MSA) and sporadic, non-mendelian Parkinson's disease (PD) are progressive neurodegenerative disorders with overlapping clinical symptoms and pathology. The etiology of both disorders is unknown, and complex combinations of multiple susceptibility genes and environmental factors are thought to be involved. Both disorders are characterized by ubiquitous alpha-synuclein aggregates in distinct regions and cell types of the central nervous system. In PD, alpha-synuclein-positive aggregates appear to be largely neuronal while in MSA oligodendroglial inclusions prevail. In PD patients, the alpha-synuclein pathology is thought to evolve in a rather regular pattern, starting in the brainstem and olfactory bulb and extending gradually onto the substantia nigra and ultimately the cerebral cortex while the cerebellum is largely spared. MSA pathology has not been graded in a similar way yet; neuropathological analyses revealed neurodegeneration and gliosis primarily in the brainstem, midbrain and basal ganglia and the cerebellum, while the cortex is largely spared. To identify disease-specific transcriptional patterns in MSA, we chose CNS regions differentially affected in MSA and PD for comparative gene expression profiling: putamen, cerebellum and occipital cortex. Four genes were regulated in both MSA and PD putamen and twelve in MSA and PD cerebellum. Regulated transcripts were validated using real-time quantitative RT-PCR, and immunohistochemistry was performed for the most significantly downregulated transcripts in MSA and PD putamen, GPR86 and RGS14, associated with G protein signaling and transcriptional regulation.

Sphincter electromyography and multiple system atrophy.

Electromyographic studies of the sphincter in patients with multiple system atrophy have shown increased duration and polyphasia of motor unit potentials. These electrophysiological markers have been used to argue for the selective degeneration of sacral motor neurons in Onuf's nucleus in patients with multiple system atrophy. Studies comparing sphincter electromyographic changes in patients with multiple system atrophy and Parkinson's disease have shown significant differences between these two patient populations. Despite the controversy surrounding this claim, recent studies using quantitative electromyographic techniques support the view that reinnervation of the anal sphincter muscles may be a useful diagnostic marker for distinguishing multiple system atrophy from Parkinson's disease. A critical review of these data is needed to assess the validity and reliability of electromyographic changes in multiple system atrophy.