MSA-C Patients Research Articles

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.

COGNITIVE DYSFUNCTION IN MULTIPLE SYSTEM ATROPHY-C

Multiple system atrophy (MSA) is a neurodegenerative disorder involving basal ganglia and frontal-subcortical circuits. Dementia represents an exclusion criterion for the diagnosis of multiple system atrophy (MSA), but there have been reports of fronto-executive dysfunction in patients with MSA of the striatonigral type (MSA-P). To study the cognitive profile of MSA, 20 patients with MSA of the cerebellar type (MSA-C) were subjected to an extensive neuropsychological test battery comprising tests for attention, verbal and visuospatial memory, as well as executive function. We assessed 20 patients affected by probable MSA-C according to the criteria of Cilman et al (Mean age:59.8±7.2; mean disease duration: 8.5±2.3; M/F=13/7) using a neuropsychological battery which included general cognitive assessment(MMSE), executive and attentive functions test (Alternating square & triangle, Luria loop, COWAT), verbal long and short term memory (SVLT, Digit span) and visual-spatial short term memory (RCFT test). We also evaluated depression and neuropsychiatric symptoms using GDS. Mean MMSE was 26.8±2.1 All patients had pathological score in Alternating square & triangle, Luria loop, COWAT. All patients had borderline scores in visual-spatial short-term memory test. All patients had depression as showed by GDS. MSA-C patients were shown to have impaired verbal memory and executive function There was evidence for impaired verbal memory and verbal fluency. Regarding the similar cognitive syndrome of MSA-P, the otherwise subclinical problems in MSA-C result from subcortical rather than from cerebellar dysfunction. Depressive thoughts occur more frequently than PD. One possible explanation for the cognitive deficits in MSA-C is to assume that parts of the cerebral cortex undergo degeneration in parallel to the pontocerebellar system.

Experimental pain sensitivity in multiple system atrophy and Parkinson's disease at an early stage.

Chronic spontaneous pain is a clinically relevant non-motor symptom in multiple system atrophy (MSA) and Parkinson's disease (PD). Experimental pain sensitivity, reflecting the mechanisms of nociception and pain perception leading to clinical pain, is known to be enhanced in both diseases at advanced stages. Also, this study aimed at investigating experimental pain sensitivity already at an early stage (i.e. symptom duration ≤5years). Experimental pain sensitivity was assessed by investigating the nociceptive flexion reflex (NFR, reflecting spinal nociception) and heat and electrical pain thresholds. 'Off-drug' MSA (n=11) and PD (n=14) patients selected at an early stage of the disease were compared to healthy controls (HC, n=27). MSA patients had either parkinsonian (MSA-P, n=5) or cerebellar (MSA-C, n=6) subtypes. Compared to HC, MSA patients had lower heat pain sensitivity, whereas PD patients had reduced NFR threshold. MSA and PD patients did not differ from HC regarding other variables. MSA-P and MSA-C patients did not differ, either. Impaired sensory discrimination and attention deficits could contribute to the reduced perception of heat pain in MSA, whereas in PD, local changes in spinal excitability or a diminished dopaminergic descending inhibition might impact on the motor efference of the NFR to reduce its threshold to nociceptive afferent information. WHAT DOES THIS STUDY ADD?: This study investigated experimental pain sensitivity at an early stage in MSA and PD.

Altered bulbocavernosus reflex in patients with multiple system atrophy

Objectives: Multiple system atrophy (MSA) is characterized by a combination of symptoms including autonomic dysfunction, parkinsonism, cerebellar ataxia, and cortico-spinal disorders. The disease can have either predominant parkinsonism or cerebellar features (MSA-P and MSA-C, respectively). The measurement of the bulbocavernosus reflex (BCR) and pudendal nerve somatosensory-evoked potentials (PSEPs) was originally developed to diagnose diabetic cystopathy and other neuropathologic diseases that share similar symptoms with MSA. We investigated the relationship between abnormalities of neurophysiological parameters and MSA, and estimated the potential value of BCR.Methods: Fifty-one MSA patients (28 and 23 MSA-P and 23 MSA-C patients, respectively) and 30 healthy controls who were seen at the Department of Neurology were included in the study. A Keypoint EMG/EP system was used to test BCR and PSEPs, and the latencies and amplitudes were recorded for statistical analyses.Results: The BCR was elicited in 78.4% patients with MSA (22/28 MSA-P, 18/23 MSA-C). Prolonged BCR latencies were found in patients with MSA compared with healthy controls (p < 0.001). BCR amplitudes were significantly lower in the MSA group than the control group (p < 0.001). PSEP P41 amplitudes were not significantly different between the MSA and control groups in males (p = 0.608) or females (p = 0.897). There were no significant differences in PSEP latencies among the MSA-P, MSA-C, and control groups (p = 1.0, p = 0.263, and p = 0.060, respectively).Discussion: MSA patients exhibit prolonged BCR latencies and lower amplitudes, which provides a rough anatomical localization of nervous system lesions in MSA patients.

Contribution of CD3 &amp;lt;i&amp;gt;ε&amp;lt;/i&amp;gt; Epitope and Oxidative Type of Copper-Zinc Superoxide Dismutase to the Degeneration Processes of Cerebellar Purkinje Cells in Patients with Multiple System Atrophy-Cerebellar Type (MSA-C: Olivopontocerebellar Atrophy, OPCA): An Immunohistochemical Study

Objective: This study aimed to investigate the contribution of CD3 epsilon (e) epitope and oxidative type of copper-zinc superoxide dismutase to the degeneration processes of cerebellar Purkinje cells in patients with Multiple System Atrophy-Cerebellar type (MSA-C). Methods: This retrospective study was carried out on autopsy specimens of 17 patients with sporadic MSA-C and 10 normal individuals. Paraffin sections of autopsied cerebella and pontes were immunostained with polyclonal antibodies against CD3 e epitope and oxidative modification to cysteine sulfonic acid of cys111 in human copper-zinc superoxide dismutase (Ox-SOD1). With respect to the areas of CD3-e-epitope expression, the immunohistochemical study and the quantitative statistical analysis between the areas of CD3-e-epitope expression in the surviving Purkinje cells of MSA-C patients and their disease duration were performed. Results: The cell bodies and dendritic arborization including primary, secondary, and tertiary dendrites of normal Purkinje cells were intensely immunostained by the antibody against CD3 e epitope. Both the immunohistochemical study and the quantitative statistical analysis revealed that the areas positive for CD3 e epitope disappeared in the order from tertiary dendrites, secondary dendrites, primary dendrites toward the cell bodies, along with the disease progression. In addition, Glial Cytoplasmic Inclusions (GCIs) and Neuronal Cytoplasmic Inclusions (NCIs) were strongly positive for CD3 e epitope. The surviving Purkinje cells in MSA-C showed immunostaining by the anti-Ox-SOD1 antibody, although normal Purkinje cells did not. Conclusion: Based on the oxidative stress that the surviving Purkinje cells in MSA-C express Ox-SOD1, the functions of morphogenesis and morphological maintenance related to CD3-e-epitope expression of the MSA-C Purkinje cells are impaired from the peripheral dendrites toward the cell bodies as the center of the Purkinje cell system. In addition, GCIs and NCIs that are pathological hallmarks of MSA also intensely express CD3 e epitope.

Characteristic diffusion tensor tractography in multiple system atrophy with predominant cerebellar ataxia and cortical cerebellar atrophy.

The objective of this study is to determine whether diffusion tensor imaging (DTI) tractography analysis is a potential method for differentiating cerebellar ataxia patients with multiple system atrophy with predominant cerebellar ataxia (MSA-C) and cortical cerebellar atrophy (CCA). Forty-one MSA-C patients (62.7 ± 8.1 years old, mean ± SD) and age- and gender-matched 15 CCA patients (63.0 ± 8.6 years old) were examined.Tractography was performed using the DTI track module provided in the MedINRIA version 1.9.4, and regions of interest were drawn manually to reconstruct an efferent fiber tract and two afferent fiber tracts via the cerebellum. Compared with CCA, MSA-C patients showed significant declines of fractional anisotropy (FA) values of afferent 1 and 2 (p<0.01, respectively) and a significant increase of the radial diffusivity (RD) value in afferent 1 (p<0.05). Receiver-operator characteristic curve analysis showed 85.7 % sensitivity and 75.0 % specificity of FA values in afferent 1 (cutoff value 0.476). Linear regressions showed strong correlations between FA value and disease duration in CCA patients (efferent 1, r = -0.466; afferent 2, r = -0.543; both p<0.05), and between the FA value and the ratio of the standardized scale for the assessment and rating of ataxia (SARA)/disease duration in MSA-C patients (afferent 1, r = -0.407; p<0.01). The present DTI tractography newly showed that the FA values of two afferent fiber tracts showed significant declines in MSA-C patients, and afferent 1 showed good diagnostic sensitivity and specificity. When combining the FA values of efferent 1 with disease duration, the present DTI tractography analysis could be useful for differentiating MSA-C and CCA patients.

The Global Cognition, Frontal Lobe Dysfunction and Behavior Changes in Chinese Patients with Multiple System Atrophy

BackgroundStudies on cognition in multiple system atrophy (MSA) patients are limited.MethodsA total of 110 MSA patients were evaluated using Addenbrooke's Cognitive Examination-Revised (ACE-R), Frontal Assessment Battery (FAB), Frontal Behavioral Inventory (FBI), and Unified MSA Rating Scale (UMSARS) tests. Fifty-five age-, sex-, education- and domicile-matched healthy controls were recruited to perform the FAB and ACE-R scales.ResultsApproximately 32.7% of the patients had global cognitive deficits with the most impaired domain being verbal fluency and visuospatial ability (26.4%), followed by memory (24.5%), language (20%) and orientation/attention (20%) based on a cut-off score of ACE-R ≤ 70. A total of 41.6% of the patients had frontal lobe dysfunction, with inhibitory control (60.9%) as the most impaired domain based on a cut-off score of FAB ≤14. Most patients (57.2%) showed moderate frontal behavior changes (FBI score 4–15), with incontinence (64.5%) as the most impaired domain. The binary logistic regression model revealed that an education level < 9 years (OR:13.312, 95% CI:2.931–60.469, P = 0.001) and UMSARS ≥ 40 (OR: 2.444, 95%CI: 1.002–5.962, P< 0.049) were potential determinants of abnormal ACE-R, while MSA-C (OR: 4.326, 95%CI: 1.631–11.477, P = 0.003), an education level < 9 years (OR:2.809 95% CI:1.060–7.444, P = 0.038) and UMSARS ≥ 40 (OR:5.396, 95%CI: 2.103–13.846, P < 0.0001) were potential determinants of abnormal FAB.ConclusionsCognitive impairment is common in Chinese MSA patients. MSA-C patients with low education levels and severe motor symptoms are likely to experience frontal lobe dysfunction, while MSA patients with low education levels and severe motor symptoms are likely to experience global cognitive deficits. These findings strongly suggest that cognitive impairment should not be an exclusion criterion for the diagnosis of MSA.

Is multiple system atrophy with cerebellar ataxia (MSA-C) like spinocerebellar ataxia and multiple system atrophy with parkinsonism (MSA-P) like Parkinson’s disease? – A saccade study on pathophysiology

ObjectivePatients with multiple system atrophy (MSA) are classified into those mainly manifesting cerebellar ataxia (MSA-C) and those mainly manifesting parkinsonism (MSA-P). Pathophysiological bases of these subtypes remain unclear. We hypothesized that MSA-C patients would resemble spinocerebellar degeneration patients and MSA-P patients would resemble Parkinson’s disease (PD) patients in saccade abnormalities. MethodsWe recorded visually guided and memory guided saccades (MGS) in 27 MSA-C and 15 MSA-P patients, as well as 50 age-matched normal subjects, 14 spinocerebellar degeneration patients showing pure cerebellar symptoms (SCD) and 61 Parkinson’s disease (PD) patients. ResultsSaccade parameters of both tasks showed similar changes with progressing disease in SCD and MSA-C patients, as did those of MSA-C and MSA-P patients, although hypometria was slightly more pronounced in MSA-P. In both subtypes of MSA, latency and success rate of MGS were stable throughout disease stages, whereas they deteriorated progressively with progressing disease in PD. ConclusionsPathophysiology underlying MSA-C and MSA-P is similar as viewed from saccade performance. The MGS performance in MSA was preserved. However, MSA-P patients showed more marked hypometria, suggesting a mixture of basal ganglia pathophysiology. SignificanceThe similarity of saccade performance between MSA-C and MSA-P may reflect common olivopontocerebellar pathology, while the direct pathway of the basal ganglia is relatively spared compared with PD, even in MSA-P.

Significance of combined use of MRI and perfusion SPECT for evaluation of multiple system atrophy, cerebellar type.

Multiple system atrophy, cerebellar type (MSA-C) sometimes shows asymmetrical findings on magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT). To assess the frequency and clinical significance of asymmetrical MRI and (99m)Tc-ethyl cysteinate dimer perfusion (ECD) SPECT findings of the cerebellum, middle cerebellar peduncle (MCP), and pons in MSA-C patients. We retrospectively reviewed 28 patients with MSA-C who underwent MRI and (99m)Tc-ECD SPECT and evaluated laterality of atrophy and signal changes on MRI, and laterality of perfusion on (99m)Tc-ECD SPECT transversely and longitudinally. Laterality was identified for 64%, 61%, and 21% of atrophy in the cerebellum, MCP, and pons, respectively, on MRI and for 71% of atrophy in the cerebellum on perfusion SPECT. Concerning comparisons between the latest MRI and SPECT findings, laterality of cerebellar/MCP atrophy on MRI and decreased cerebellar perfusion on SPECT was matched in 57%, mismatched in 11%, and absent in 25% of patients. On past images, MRI and SPECT showed matched laterality in 33%, mismatched laterality in 27%, no laterality in 13%, and SPECT precedent laterality in 27% of patients. Including the latest and past images, asymmetrical changes were observed in 75% of patients. We could not identify any correlation between laterality of image findings and cerebellar symptoms in most patients. Asymmetrical changes on MRI and perfusion SPECT are common in MSA-C patients. Perfusion SPECT is useful for diagnosing MSA-C in the early stages from a functional perspective.

1-P-E-6. Saccade abnormalities in multiple system atrophy – Comparison between MSA-C and MSA-P

Multiple system atrophy (MSA) is classified into subtypes mainly showing cerebellar ataxia (MSA-C) and parkinsonism (MSA-P). To characterize the pathophysiological difference between the two subtypes, we recorded performances of visually guided (VGS) and memory guided saccade (MGS) tasks in 27 MSA-C patients, 14 MSA-P patients, 14 patients with spinocerebellar degeneration (SCD) exhibiting pure cerebellar symptoms, 61 Parkinson’s disease (PD) patients, and 50 age-matched normal subjects. Compared to normal subjects, VGS latency was prolonged and VGS accuracy reduced in all patient groups, and the changes progressively deteriorated with advancing disease. In contrast, the latency and success rate of MGS stayed similar to the normal level throughout the disease stages for SCD, MSA-C, and MSA-P patients, whereas in PD patients, both latency and success rate of MGS deteriorated progressively with advancing disease. MGS amplitude was reduced compared to normal subjects and deteriorated progressively with advancing disease stage in MSA-P and PD patients, but not in SCD patients. The results suggest that in terms of saccade latency MSA shows changes more similar to SCD, indicating that function of the direct pathway of the basal ganglia is relatively preserved compared with PD. Meanwhile, MGS amplitude in MSA-P shows a decline similar to PD patients.

Significance of the hot-cross bun sign on T2*-weighted MRI for the diagnosis of multiple system atrophy.

Although the sensitive detection of putaminal iron deposition by T2*-weighted imaging (T2*-WI) is of diagnostic value for multiple system atrophy (MSA), the diagnostic significance of the pontine hot-cross bun (HCB) sign with increased ferritin-bound iron in the background remains unknown. We retrospectively evaluated the cases of 33 patients with cerebellar-form MSA (MSA-C) and 21 with MSA of the parkinsonian form (MSA-P) who underwent an MRI study with a 1.5-T system. Visualization of the HCB sign, posterior putaminal hypointensity and putaminal hyperintense rim on T2*-WI was assessed by two neurologists independently using an established visual grade, and were compared with those on T2-weighted imaging (T2-WI). The visual grade of pontine and putaminal signal changes was separately assessed for probable MSA (advanced stage) and possible MSA (early stage). T2*-WI demonstrated significantly higher grades of HCB sign than T2-WI (probable MSA-C, n = 27, p < 0.001; possible MSA-C, n = 6, p < 0.05; probable MSA-P, n = 13, p < 0.01). The visual grade of the HCB sign on T2*-WI in the possible MSA-C patients was comparable to that in the probable MSA-C patients. Although the HCB sign in MSA-P was of lower visual grade than in MSA-C even on T2*-WI, some patients showed evolution of the HCB sign preceding the appearance of the putaminal changes. These findings suggest that T2*-WI is of extreme value for detecting the HCB sign, which is often cited as a hallmark of MSA. The appearance of the HCB sign on T2*-WI might not only support but also improve the diagnosis of MSA.

“Cerebellar peduncle quarter notes” formed by the superior and middle cerebellar peduncles: comparison with a diffusion tensor study of spinocerebellar degeneration

To investigate morphological changes of the superior and middle cerebellar peduncles (SCP, MCP) in spinocerebellar degeneration (SCD) by observing "cerebellar peduncle quarter notes". We examined 21 patients with SCD, including nine patients with multiple system atrophy cerebellar type (MSA-C), and 24 controls. We measured SCP angle and performed diffusion tensor analysis to quantify the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) of the MCP. We quantified the relationship between SCP angle and the ADC and FA of the MCP, and compared these variables between MSA-C patients and controls. There was statistically significant negative correlation between SCP angle and FA of the MCP, and a positive correlation between SCP angle and the ADC of the MCP. Mean SCP angle was larger among MSA-C patients than among normal controls. SCP angle tended to be larger among patients with severe degeneration of the MCP. The SCP angle, quantified by observing "cerebellar peduncle quarter notes", may be a simple index for evaluation of degeneration of the MCP.

Simultaneous assessment of cognitive and affective functions in multiple system atrophy and cortical cerebellar atrophy in relation to computerized touch-panel screening tests

Cognitive impairment and affective dysfunction of multiple system atrophy (MSA) and cortical cerebellar atrophy (CCA) have not been simultaneously examined comparing standard test batteries and a sensitive tool to detect subtle cognitive decline in patients. In the present study, we simultaneously examined cognitive and affective ability in MSA with predominant cerebellar ataxia (MSA-C, n=25), MSA with predominant parkinsonism (MSA-P, n=8), and CCA (n=14) patients using computerized touch panel screening tests. Mini-mental state examination (MMSE), Hasegawa dementia scale-revised (HDS-R), frontal assessment battery (FAB), and Montreal cognitive assessment (MoCA) scores were significantly lower in MSA-C patients than in age-and gender-matched normal controls. One MSA-C patient showed a decrease in the regional cerebral blood flow (rCBF) of the frontal lobe. MSA-P patients showed no such cognitive decline. Only FAB and MoCA scores were significantly lower in the CCA patients. MSA and CCA patients also showed a mild to moderate depressive state. Touch-panel screening tests demonstrated a significant decline of beating devils game in all three disease groups including MSA-P patients, and a significant extension of the flipping cards game only in MSA-C patients. The present study demonstrated different cognitive and affective functions among MSA-C, MSA-P, and CCA patients, and a sensitive screening method for cognitive assessment using touch-panel tests.

Cerebrospinal Fluid Biomarkers in Spinocerebellar Ataxia: A Pilot Study.

Neurodegenerative diseases, including the spinocerebellar ataxias (SCA), would benefit from the identification of reliable biomarkers that could serve as disease subtype-specific and stage-specific indicators for the development and monitoring of treatments. We analyzed the cerebrospinal fluid (CSF) level of tau, α-synuclein, DJ-1, and glial fibrillary acidic protein (GFAP), proteins previously associated with neurodegenerative processes, in patients with the autosomal dominant SCA1, SCA2, and SCA6, and the sporadic disease multiple system atrophy, cerebellar type (MSA-C), compared with age-matched controls. We estimated disease severity using the Scale for the Assessment and Rating of Ataxia (SARA). Most proteins measured trended higher in disease versus control group yet did not reach statistical significance. We found the levels of tau in both SCA2 and MSA-C patients were significantly higher than control. We found that α-synuclein levels were lower with higher SARA scores in SCA1 and tau levels were higher with greater SARA in MSA-C, although this final correlation did not reach statistical significance after post hoc correction. Additional studies with larger sample sizes are needed to improve the power of these studies and validate the use of CSF biomarkers in SCA and MSA-C.

Autonomic predominant multiple system atrophy in the context of Parkinsonian and cerebellar variants

ObjectivesAutonomic dysfunction is often a late feature of multiple system atrophy (MSA). Based on early features, MSAp (Parkinsonian) and MSAc (cerebellar) variants are known. We studied the severity of autonomic dysfunction at first examination in MSA patient that may have relevance in its early diagnosis. MethodsClinical (including autonomic), radiological and lab features of 53 MSA patients were analyzed in the context of MSAp (16 patients) and MSAc (37 patients). ResultsMost frequent autonomic symptoms were erectile dysfunction in 30 out of 38 males (78.9%), bladder symptoms in 35 (66%), followed by blackouts/fainting attacks in 33 (62.3%). Autonomic abnormalities were detected in hand grip test (86.8%), deep breathing test (79.2%), cold pressor test (71.7%), Valsalva maneuver (75.5%), heart rate variability at 30:15 beats after standing (50.9%) and systolic BP on standing (41.5%). Six (16.2%) MSAp and 1 (6.3%) MSAc patients continued to have autonomic symptoms for several months (38.7±26.11, median 36 months) before the appearance of cerebellar (1 patient) or Parkinsonian (6 patients) features. ConclusionAutonomic dysfunction may be the only presenting feature in some patients with MSA. Routine autonomic testing may help in the early diagnosis of MSA in patients presenting with Parkinsonian or cerebellar features.

A Cross-Sectional Study on Drug Use in Multiple System Atrophy

Drug use has rarely been studied in multiple system atrophy (MSA) while such patients receive many treatments based on weak evidence. To analyze drug use from the database of the French MSA Reference Center, and to compare it with data from patients with Parkinson disease (PD). Medication of 147 MSA and 180 age- and sex-matched PD patients was analyzed. Motor and autonomic symptoms were explored in MSA patients by the SCOPA-Autonomic and Unified MSA Rating Scale (UMSARS). MSA and PD patients received a mean of five different drugs. MSA patients were more frequently exposed to laxatives, antidiabetic medications, antihypotensives, muscarinic antagonists, alpha-adrenergic blockers, and antidepressants. Levodopa consumption was less in MSA-C (cerebellar) patients compared with MSA-P (parkinsonian) and PD patients. Dopamine agonists were more consumed by PD than MSA patients. MSA patients with more severe disability received more laxatives, anticoagulants, and antidepressants. MSA-P patients received more analgesics. "Probable" MSA patients received more antihypotensives and less alpha-adrenergic blockers. Patients with higher SCOPA-Autonomic scores were more frequently on antihypotensives or antidepressants. Drug associations leading to potential adverse interactions were uncommon (usually <5%). Some differences in drug use between MSA and PD patients were observed and expected, including those used for the relief of parkinsonian motor symptoms, autonomic dysfunction, and depression. Many of these drugs are frequently used in MSA in the absence of well-established, positive, benefit-risk evaluations, thus calling for better assessments. The reason why other medications, including anti-diabetic medications, were more consumed by MSA patients remains unclear and deserves further exploration.

Blinking in patients with clinically probable multiple system atrophy

Clinical studies in patients with MSA document facial motor abnormalities, but no studies have objectively assessed blinking abnormalities in this condition. We enrolled patients diagnosed as having clinically probable MSA, 20 patients of the parkinsonian phenotype (MSA-P) and 10 patients of the cerebellar phenotype (MSA-C) and 20 healthy controls (HCs). Blinking was recorded with a three-dimensional optoelectronic motion system equipped with dedicated software for data analysis. During voluntary blinking, the interphase pause duration between the closing and opening phases lasted longer in MSA-P and in MSA-C patients than in HCs; the opening phase had increased duration and reduced peak velocity in MSA-P. During reflex blinking, the opening blink phase also lasted longer in MSA-P patients than in HCs. During spontaneous blinking, the rate and kinematics of the closing and opening blinking phases were lower in MSA-P and in MSA-C patients than in HCs. Blink reflex recovery was higher in patients than in HCs. No difference was found between MSA-P patients receiving or not receiving dopaminergic medication. Our objective assessment of upper facial movement documents abnormalities of voluntary, spontaneous, and reflex blinking in patients with MSA-P and MSA-C, reflecting cortical-basal ganglia and brainstem dysfunction.

Pan-American Consortium of Multiple System Atrophy (PANMSA). A Pan-American multicentre cohort study of multiple system atrophy.

Multiple system atrophy (MSA) is an adult-onset and rapidly progressive, neurodegenerative condition that presents with autonomic dysfunction, parkinsonism, cerebellar ataxia and corticospinal deficits. Clinical, demographic and epidemiological data from different regions have provided valuable information concerning the natural history of MSA. There are no published data of Multiple System Atrophy (MSA) in Latin American countries. To describe clinical and epidemiological data of patients with "possible" MSA from seven referral movement disorders centers from Argentina, Chile, Mexico, Peru and United States. We conducted a retrospective, observational, cross-sectional Pan-American multicentre cohort study of MSA. The sample was composed of 82 females and 77 men with the diagnosis of "possible" MSA with a mean age at onset of 65 ± 10 years. 67.29% of the individuals had a MSA-P variant with a mean age at onset of 61.47 ± 10.28 years, whereas the mean age at onset in the MSA-C patients was 57.44 ± 10.58 years. Interestingly, MSA-C-was more prevalent in Non-Caucasian (50-Mestizo and 2 Asian patients) than Caucasians (51.92% vs. 20.79%, p = 0.0001). Dysautonomic symptoms were present in 95.6% of the patients, parkinsonism in 85.5%, pyramidal signs in 25.8% and depression in 48.4% of the patients. Our epidemiological and clinical data appears to be similar to other Western international series, however, of note, the MSA-C phenotype was predominant in Non-Caucasians, more specifically the Mestizo population. This observation opens a new path to explore. Larger prospective epidemiologic studies in Latin America may provide valuable information concerning MSA in the region.

Analysis of fragile X mental retardation 1 gene premutation in multiple system atrophy patients

To investigate whether Chinese multiple system atrophy (MSA) patients have premutation of fragile X mental retardation 1 gene(FMR1). FMR1 CGG repeats were analyzed in 157 MSA patients by polymerase chain reaction, agarose gel electrophoresis and capillary electrophoresis. The patients were collected from Movement Disorder & Neurogenetics Research Center of China-Japan friendship hospital. There were 83 male cases and 74 female cases, including 51 MSA-C patients, 12 MSA-P patients and 94 MSA-P+C patients. No FMR1 CGG repeat premutation was detected in 157 MSA patients. The repeats ranged from 11-49, most common allele was 22. A MSA-C case carried 35/49 alleles did not have middle cerebellar peduncles(MCP) sign which was necessary for the diagnosis of fragile X associated tremor ataxia syndrome(FXTAS). The FMR1 premutation in Chinese MSA patients might be very rare.

Elevated titers of anti-thyroperoxidase antibodies in patients with multiple system atrophy: A pilot study

ObjectivesMultiple system atrophy (MSA) is a neurodegenerative disease characterized by progressive neuronal loss and alpha-synuclein deposition in oligodendroglial cells in the central nervous system. The cause of MSA remains essentially unknown. A cerebellar syndrome was associated with autoimmune thyroid disease in some cases, apparently not related to MSA and was partially responsive to immunomodulatory therapy. Patients and methods28 euthyroid patients who fulfilled the diagnostic criteria for probable MSA, 11 with MSA-cerebellar type (MSA-C), 17 with MSA-parkinsonian type (MSA-P), 28 patients with Parkinson's disease (PD) and 26 normal euthyroid controls were tested the for serum levels of anti-thyroperoxidase antibodies (anti-TPO) and anti-thyroglobulin (Anti-TG) antibodies (Ab). ResultsThe laboratory results were statistically similar in all three groups, but 3 MSA-C patients had highly elevated anti-TPO Ab titers. ConclusionWe identified the presence of elevated anti-TPO levels in a small subgroup of MSA-C patients but neither in MSA-P or PD patients nor in healthy controls. These findings may suggest an autoimmune etiology in some cases of MSA-C.