September 2026 Research Update

Across these studies, the overall pattern is that multiple system atrophy (MSA) can leave detectable signals in the brain (on MRI and EEG) and in body-based markers (skin, blood, urine, and serum chemistry) that differ from Parkinsons disease (PD) and sometimes from other conditions. Some tests looked most useful for separating groups on average, while others appeared more helpful when added to usual clinical information. Many studies were retrospective or small, so it is still uncertain how well these approaches work across different clinics and populations. [1] [2] [3] [4] [5] [6] [7] [8] [9]

Several MRI studies reported differences in brain measurements, including those involving the putamen, cerebellum, and connected pathways, between people with MSA, Parkinson's disease, and progressive supranuclear palsy (PSP). These findings come from group comparisons and do not establish that the measurements can reliably diagnose an individual patient. One imaging study found that putaminal volume and a diffusion MRI measure of free fluid differed across PD, MSA, PSP, and healthy controls, while one T1 measure did not show clear group differences. [4] [5]

In another diffusion MRI study, a compact set of diffusion features across selected brain regions achieved high discrimination in their dataset, including PD versus MSA and PSP versus MSA comparisons. The authors highlighted the putamen, corpus callosum, and cerebellum as key regions that helped distinguish these conditions, but noted the need for validation beyond a single center. [5]

A separate longitudinal MRI and machine learning study created a subject-level heterogeneity score based on structural and diffusion MRI measures, which differentiated MSA subtypes from PD and also tracked change over 12 months in relation to symptom progression scores. This suggests MRI-based pattern tools might eventually help with both distinguishing diagnoses and monitoring how the disease pattern changes over time, but the study was small and needs external validation. [6]

Two studies evaluated non-imaging, clinic-friendly testing ideas for differentiating MSA from other parkinsonian syndromes. A quantitative scoring approach for the simple pentagon-copying item on the Mini-Mental State Examination separated PD from atypical parkinsonian syndromes with high specificity but relatively low sensitivity at the proposed cutoff, meaning it may miss some people even if it helps rule in group-level differences. [3]

An EEG (electroencephalogram) connectivity study reported different network disruption patterns in MSA-P versus PD: MSA-P showed reduced beta-band amplitude connectivity, while PD showed phase-based decoupling in delta and beta bands. When combined with clinical assessments, EEG network features provided a modest gain for distinguishing PD from MSA-P in an exploratory machine-learning analysis. [2]

Several studies focused on body-fluid or tissue markers that could be less invasive than brain imaging or spinal fluid testing. A urine test that enriched neuronal extracellular vesicles and used a seeding assay detected disease-related alpha-synuclein seeds with moderate sensitivity and high specificity versus healthy controls, and reported stronger assay signals in both Parkinsons disease and MSA than in control groups. [9]

Blood-based markers also showed group differences, but are not yet definitive for individual diagnosis. In one study, whole-blood mitochondrial DNA copy number was lower in both PD and MSA than in healthy controls, and PD was lower than MSA, while telomere length was also reduced in PD and MSA with smaller differences between the two diseases. [7]

A serum metabolomics study identified a riboflavin-xanthine panel that separated MSA from healthy controls with high accuracy in internal and external validation sets, and reported that lower xanthine slightly improved the diagnostic performance of an existing blood marker when distinguishing MSA from PD in their cohort. The same paper also included lab (cell) experiments suggesting riboflavin and xanthine can affect cell health in alpha-synuclein overexpression models, which is background research rather than a clinical test result. [8]

Finally, a real-world chart review in a private neurology practice examined skin biopsy testing for phosphorylated alpha-synuclein in people with movement or cognitive symptoms, and found the test result frequently changed the documented diagnosis category and/or the treatment plan after results were returned. Because the study was retrospective and relied on clinician assessment rather than a definitive reference standard, it mainly shows how the test influenced clinical decision-making in that setting. [1]

For patients and caregivers, this group of papers mainly adds context about why diagnosis can change over time and why specialists may use multiple types of tests (brain imaging, brain electrical activity, and body-based markers) to clarify whether symptoms fit MSA or another condition like Parkinsons disease. Some approaches (like advanced MRI measures, metabolomics panels, urine seeding assays, and EEG connectivity patterns) are still in the validation stage, meaning it remains uncertain how consistent they will be across hospitals and scanners, and how well they perform for an individual person rather than group averages. The skin biopsy chart review suggests that, in at least one real-world clinic, biomarker results can strongly influence how clinicians label and manage a case, but it does not prove the biomarker is always correct for every patient.

Across these papers, a consistent pattern is that sleep problems in multiple system atrophy (MSA) can involve both breathing changes during sleep and broader sleep disruption, and these issues may be tightly connected to problems in automatic body functions like blood pressure control. The research also highlights uncertainty about timing and warning signs, because severe breathing failure may occur even without the classic symptom of stridor. [10] [11]

In a retrospective cross-sectional study of people with sleep complaints who had not yet started disease-related medicines, MSA showed worse sleep and worse autonomic (automatic) function than Parkinsons disease (PD). People with MSA had more breathing interruptions during sleep (higher apnea-hypopnea index), lower lowest overnight oxygen levels, and less deep sleep, alongside larger blood pressure drops on standing and higher overall autonomic impairment scores. [10]

The same study used statistical modeling suggesting that, in MSA, worse autonomic dysfunction tracked more strongly with worse sleep disruption than it did in PD. Because the study was cross-sectional, it cannot show whether autonomic changes cause sleep disruption, whether sleep disruption worsens autonomic function, or whether both are driven by other disease features. [10]

A separate case report described one 81-year-old woman with MSA who developed acute respiratory failure tied to severe obstructive sleep apnea syndrome before she developed laryngeal stridor. Sleep testing confirmed obstructive sleep apnea, and throat exam showed mild vocal cord weakness without stridor; after breathing tube removal, high carbon dioxide levels during sleep persisted and noninvasive ventilation was needed. This is a single-patient report, so it may not reflect what happens in others. [11]

For patients and caregivers, these studies mainly add context about why sleep in MSA can be complicated: breathing interruptions during sleep, low oxygen, and fragmented sleep may occur alongside autonomic problems such as blood pressure drops, and these may move together. The case report is a reminder that severe sleep-related breathing failure can sometimes appear even when stridor is not yet present, but it does not indicate how common this is. What remains uncertain is which symptoms best predict risk in an individual person and whether improving one problem (sleep or autonomic function) reliably improves the other.

This paper suggests that teeth grinding or jaw clenching during sleep (sleep bruxism) may look different in multiple system atrophy (MSA) than in other Parkinson-like conditions, with a tendency toward more sustained (tonic) jaw-muscle activation. The evidence is early because the study was small and retrospective. [12]

In overnight sleep studies that included recordings from both jaw muscles, the MSA group had a higher number of tonic bruxism events than the comparison group with Parkinsonian-related disorders. Bruxism episodes during rapid eye movement (REM) sleep were also more frequent in MSA, and these REM episodes were usually tonic or mixed rather than purely brief (phasic). [12]

Some measures did not reach statistical significance, such as the percentage rate of tonic activity, which the authors noted as a limitation along with the small sample size. This means the exact size of any difference is uncertain, and results may not generalize to all people with MSA. [12]

For patients and caregivers, this study mainly serves as background research showing that sleep-related jaw muscle activity may be part of the sleep picture in MSA and may differ from other Parkinson-like disorders. It does not establish how often bruxism happens in MSA overall, whether it changes over time, or whether it is linked to other symptoms such as breathing problems or daytime jaw pain. Larger studies would be needed before these sleep-lab patterns could be used to guide routine care discussions.

Across this months treatment and safety papers, results were mixed: one controlled trial reported short-term improvement in movement and walking with a non-drug brain stimulation approach, while a separate drug study highlighted a specific safety concern affecting the liver. A small case report also described a specialized psychiatric treatment that appeared to help both mental health and movement symptoms in one person with multiple system atrophy (MSA), but this evidence is limited to individual cases. Some biological signals (brain connectivity changes and a genetic risk marker) were reported, but both were described as exploratory and not yet confirmed. [13] [14] [15]

In a randomized, double-blind, placebo-controlled trial in cerebellar-type MSA (MSA-C), 2 weeks of daily transcranial alternating current stimulation (tACS) improved the main MSA rating scale score compared with sham stimulation, and also improved ataxia (coordination) and gait measures. The study reported no treatment-related serious side effects, while quality of life and autonomic symptom scores did not show improvement over the short study period. Brain scan analyses did not show clear between-group differences after statistical correction, and the authors described the connectivity findings as hypothesis-generating. [13]

In a Phase 2 randomized trial of the drug KM-819 in Korean adults with probable or possible MSA, suspected drug-induced liver injury was seen in 11 of 34 treated participants, and 9 cases were adjudicated as related to KM-819; no cases were reported in the placebo group. In an exploratory genetic analysis of 16 participants, one specific immune-system gene type (HLA-DPB1*05:01:01:01) was present in all 6 people with liver injury and in 1 of 10 without liver injury, which the authors said needs confirmation in larger and more diverse groups. Because this genetic work was small and exploratory, it cannot yet be used to reliably predict risk in general MSA populations. [14]

A two-patient case series described maintenance electroconvulsive therapy (mECT) used to prevent relapse of psychiatric symptoms in parkinsonian conditions, including one person with MSA who had severe depression with psychosis. In that MSA case, symptoms improved markedly after electroconvulsive therapy, and continued maintenance treatment prevented a return of movement symptoms at 1 month; in the other case, a person with Parkinsons disease, the authors reported no cognitive decline. Because this describes only one person with MSA, it is uncertain how often similar results would occur in others. [15]

For patients and caregivers, these papers mainly add context about what is being tested and what safety issues are being watched. The tACS study suggests short-term improvements in coordination and walking may be possible in MSA-C with a non-drug approach, but longer-term effects and who benefits most are still unknown. The KM-819 study is a reminder that drug development in MSA can uncover important safety problems, including liver injury, and that genetic risk signals may emerge but usually require larger follow-up studies before they can be considered reliable. The electroconvulsive therapy report is relevant mainly for people facing severe depression or psychosis alongside parkinsonism, but it is based on single-patient experience in MSA and cannot predict typical outcomes.

Across these papers, care models focused on late-stage swallowing and breathing risks and on organizing long-term supportive care. One hospital-based study suggested that starting tube feeding within a structured care pathway was linked to modestly longer survival and fewer sudden deaths, while a small surgical series aimed at preventing aspiration showed no pneumonia-related deaths. A separate clinic report suggested that ongoing interdisciplinary supportive care is feasible for advanced parkinsonism (including multiple system atrophy) and was paired with high hospice use among those who died. [16] [17]

In a single-center retrospective cohort of 158 adults with probable or definite multiple system atrophy (MSA), people who received enteral nutrition (tube feeding) had longer survival than similar people who did not after propensity-score matching, with a restricted mean survival time difference of 0.68 years. Sudden death was less common in the enteral nutrition group (15% vs 30%), although the enteral nutrition group had a higher incidence of tracheostomy or tracheostomy invasive ventilation over time. The authors noted key limits, including the retrospective design, possible remaining differences between groups, and lack of quality-of-life data. [16]

The same study also described laryngotracheal separation, a surgical approach intended to reduce aspiration into the lungs, in a small series of people with MSA. In that series, there were no pneumonia-related deaths after the procedure, and some people were able to keep a limited amount of oral intake. Because this was a small, single-center experience, it is uncertain how well these results apply to broader groups of patients. [16]

In a separate retrospective chart review of an Advanced Interdisciplinary Movement Disorders Supportive Care (AIMS) clinic, 175 people with late-stage parkinsonism (including 12.6% with MSA) were followed over 568 visits, and almost all were accompanied by a care partner (97.5%). Among the 58 people who died, 69.0% were enrolled in hospice at the time of death. The report focused on feasibility and care patterns rather than directly comparing outcomes to usual care. [17]

For patients and caregivers, these papers add context about how some centers approach later-stage MSA when swallowing problems and aspiration risk become major concerns, and how care can be organized over time. The tube-feeding and airway-surgery results come from retrospective, single-center experience, so they cannot prove that these steps will help every person or clarify trade-offs such as day-to-day comfort or communication. The clinic model study mainly serves as background on care delivery, showing that regular interdisciplinary visits with strong caregiver participation are possible and that hospice enrollment at death was common in that setting, but it does not show which specific clinic components led to those outcomes. [16] [17]

Across this month s research in mood and motivation, one study suggests that apathy in multiple system atrophy (MSA) is not just a reaction to disability or depression, but may reflect specific changes in brain function. In a moderate sized, cross sectional study limited to people with preserved overall cognition, apathy was frequent and tracked with distinct patterns on a brain blood flow scan. [18]

In 76 people with clinically established or probable MSA and high Mini Mental State Examination scores, 55.3% met criteria for apathy on a standard apathy questionnaire. The apathy group had similar depression scores compared with the non apathy group, suggesting apathy and depression did not fully overlap in this sample. [18]

People with apathy had lower visuospatial test scores, meaning more difficulty with tasks like understanding shapes or space. They were also less likely to have neurogenic orthostatic hypotension (a drop in blood pressure on standing caused by nerve problems), though this does not explain apathy on its own. [18]

On a brain blood flow scan (SPECT), apathy was linked to reduced blood flow in the medial prefrontal region (part of the frontal lobe involved in motivation and goal directed behavior). The same analysis suggested weaker coordinated activity between this frontal region and posterior parts of the cerebellum, pointing to possible involvement of cerebellar networks that support thinking and emotion. [18]

For patients and caregivers, this research supports the idea that apathy can be a common symptom in MSA and may reflect brain network changes rather than depression alone. It mainly adds background understanding right now, because the study was cross sectional (a snapshot in time) and cannot show what causes apathy or how it changes. It is also uncertain how well these results apply to people with more cognitive changes, since the study focused on those with preserved cognition. [18]

Across this post-mortem brain study, a consistent pattern emerged in oligodendrocytes (support cells that help nerve fibers): these cells more often carried extra copies of the SNCA gene (which makes alpha-synuclein), and they also showed more signs of DNA damage. Extra copies of the alpha-synuclein gene were associated with alpha-synuclein clumps and earlier symptom onset, while a marker of DNA damage was more common in heavily affected brain regions and cells containing clumps. The study did not establish which changes occurred first. [19]

In brain regions typically affected in multiple system atrophy (MSA), oligodendrocytes more often had SNCA copy number gains in MSA than in controls, and the regional burden of these gains rose alongside the amount of alpha-synuclein pathology. At the single-cell level, oligodendrocytes with SNCA gains were more than twice as likely to contain alpha-synuclein inclusions in the regions where MSA changes were strongest. [19]

The same study also found more SNCA copy number losses in MSA than controls, although these losses were less tied to specific brain regions than gains. Separately, a marker of DNA double-strand breaks (gamma-H2AX) was higher in MSA, especially in oligodendrocytes and in cells that contained alpha-synuclein inclusions. [19]

When the researchers compared people within the MSA group, a higher burden of SNCA gains correlated with a younger age of symptom onset. This suggests that, at least in these brain samples, having more oligodendrocytes with extra SNCA copies went along with a more "early-starting" form of disease, though it does not show this is the cause. [19]

This research mainly helps explain what may be happening inside brain cells in MSA rather than changing care now. It supports the idea that MSA may involve gene copy changes arising in certain cells during life (not inherited), along with increased DNA damage, and that these may relate to alpha-synuclein buildup in oligodendrocytes. What remains uncertain is the order of events (for example, whether DNA damage leads to gene copy changes or the reverse) and how these findings vary from person to person, since the work was done in post-mortem tissue.