Atypical Parkinsonism Spotlight: Multiple System Atrophy (MSA)

Not long ago, I evaluated a patient recently diagnosed with Parkinson’s disease who presented with symptoms that seemed, at first, like the usual advanced autonomic involvement seen in PD. His primary concern was severe constipation that had progressed to fecal impaction, something he described as worsening rapidly over a matter of weeks. As I continued the examination, other signs emerged: lightheadedness after standing, unpredictable blood pressure swings, and a gait pattern deteriorating far faster than I would expect in typical PD. The combination of severe gastrointestinal dysfunction and early, profound autonomic instability eventually pushed the diagnosis away from Parkinson’s disease and toward, what I believe, was Multiple System Atrophy (MSA), a disorder that challenges clinicians in ways few neurodegenerative diseases do.

What Is Multiple Systems Atrophy?

Multiple System Atrophy is a progressive, adult-onset neurodegenerative disorder classified under the atypical Parkinsonisms. Unlike idiopathic Parkinson’s disease, which is primarily driven by dopaminergic neuron loss in the substantia nigra, MSA involves widespread degeneration across the basal ganglia, cerebellum, brainstem, and autonomic pathways. The underlying pathology centers on the accumulation of α-synuclein within oligodendrocytes rather than neurons, an important distinction because it creates a pattern of failure that affects several major systems simultaneously rather than producing a primarily motor disorder.

Subtypes Within a Subtype

Clinically, MSA falls into two major subtypes.

1. MSA-P:

   1. The parkinsonian variant, resembles PD in its early motor presentation with bradykinesia, rigidity, and postural instability, yet typically responds poorly to levodopa.

2. MSA-C

   1. The cerebellar variant, presents with ataxia, dysarthria, limb incoordination, and gait instability driven by cerebellar degeneration. Although many patients lean toward one subtype initially, symptoms often blend as the disease progresses.

Diagnosing MSA

Diagnosis remains clinical, supported by imaging and autonomic testing. The most defining clinical requirement is the presence of significant autonomic dysfunction (urinary incontinence, orthostatic hypotension, erectile dysfunction, or severe bowel dysmotility) paired with either poorly responsive parkinsonism or cerebellar ataxia. MRI may reveal characteristic indicators such as putaminal changes or the “hot cross bun” pontine sign, while autonomic testing and urodynamic studies help clarify the extent of system involvement. The diagnosis is often delayed because symptoms overlap with PD initially, yet the speed and severity of decline tend to be the major clues.

Signs and Symptoms That Distinguish MSA from Typical PD

Multiple System Atrophy is defined by its early, aggressive, and multisystem pattern of decline. The symptom that most clearly distinguishes it from Parkinson’s disease is severe orthostatic hypotension, with patients experiencing dramatic blood pressure drops, can be up to 40 to 60 mmHg, within seconds-minutes of standing. This leads to dizziness, visual dimming, nausea, or collapse during simple transitions. In contrast, many patients also develop supine hypertension, creating a highly unstable blood pressure profile that oscillates between dangerous highs when lying flat and profound lows when upright, far more characteristic of MSA than PD.

Autonomic dysfunction is widespread. Urinary symptoms such as urgency, frequency, retention, or incontinence often appear early and worsen quickly. Gastrointestinal involvement, especially severe constipation and slow motility, can progress to fecal impaction or megacolon. These autonomic issues frequently precede or overshadow the motor symptoms.

Motor involvement often blends parkinsonian and cerebellar features. Patients may demonstrate ataxia, limb incoordination, and slurred or scanning speech alongside bradykinesia and rigidity, yet these symptoms typically show minimal response to levodopa. Postural instability occurs early, leading to rapid declines in ambulation and early need for assistive devices.

Bulbar dysfunction emerges earlier than in PD. Dysarthria and dysphagia progress quickly, impairing communication and increasing aspiration risk.

Importantly, dementia is uncommon in MSA, especially in the early and middle stages. The preservation of cognition, despite severe autonomic and motor decline, helps differentiate MSA from conditions like Parkinson’s disease dementia or dementia with Lewy bodies, where cognitive impairment is a core feature.

Taken together, the combination of profound OH, paradoxical supine hypertension, early urinary and GI dysfunction, cerebellar involvement, rapid bulbar decline, and relative cognitive preservation forms a clinical picture that is distinct from idiopathic Parkinson’s disease and critical for therapists to recognize early.

PT’s Fancy Tests to Assist in Diagnosis

Tilt-table testing provides a structured assessment of autonomic cardiovascular function and is especially useful when patients report unexplained dizziness, presyncope, or difficulty tolerating upright positions. For individuals with MSA, the test helps quantify the severity of autonomic failure, guides medication adjustments, and may serve as a graded exposure tool to safely improve upright tolerance. Patients who struggle with standing long enough to complete basic therapy tasks often benefit the most, as tilt-table training allows the cardiovascular system to adapt gradually without the risk of falls. For more information on tilt table testing, check out our previous article on OH management and tilt table utilization.

Managing Autonomic Dysfunction: What PTs Can Do

Non-pharmacologic interventions are essential and fall squarely within the physical therapist’s domain. Abdominal binders can meaningfully improve standing blood pressure by enhancing venous return, while graduated compression garments support venous tone in the lower extremities. Adequate hydration and increased salt intake, when appropriate, further stabilize blood pressure. Physical counter-maneuvers, such as leg crossing, sustained muscle contractions, and isometric handgrip, provide immediate but temporary boosts in vascular resistance. Functional training that incorporates slow, controlled transitions from supine to sitting to standing helps “train” the autonomic system and improves tolerance to daily positional stressors. Elevating the head of the bed reduces nocturnal diuresis and helps mitigate morning hypotension, when symptoms are often worst.

Pharmacologic Management of Automatic Symptoms

Neurologists and autonomic specialists frequently prescribe medications such as midodrine, fludrocortisone, droxidopa, or pyridostigmine to combat OH. Botulinum toxin injections may help bladder dysfunction, and nighttime respiratory support can be crucial for patients experiencing stridor. Physical therapists play an important role in understanding these medications, as their timing and side effects significantly impact session safety and tolerance to activity.

Motor Symptom Management Through Rehabilitation

Because MSA responds poorly to dopaminergic therapy, physical therapy becomes one of the most important drivers of mobility maintenance. High-intensity gait training, postural control exercises, external cueing, balance training, and power-based strengthening are all beneficial in the early stages. As the disease progresses, therapists must anticipate upcoming mobility transitions, introducing assistive devices earlier than they might for PD, addressing wheelchair needs proactively, and identifying when orthotics may improve safety or reduce energy expenditure. In MSA-C especially, targeting ataxia through coordination and stability strategies becomes central to care.

The Course of Disease and Typical Prognosis

MSA progresses more rapidly than Parkinson’s disease. Most individuals require a wheelchair within five years of symptom onset, and average life expectancy falls between six and ten years after initial presentation. Respiratory complications, infections, and severe autonomic failure often drive the later decline. Recognizing the progressive nature of the disease allows therapists to help patients and families prepare for transitions, preserving safety, dignity, and quality of life throughout the disease course.

Why Physical Therapy Still Matters: Evidence

A pivotal study published in 2020 examined the effects of intensive inpatient rehabilitation on individuals with atypical Parkinsonism, including MSA. Despite the rapid disease progression and poor response to medication, participants demonstrated meaningful improvements in gait performance, balance metrics, and functional independence following structured rehabilitation. These gains highlight a crucial message for clinicians: even when the neurodegenerative process cannot be slowed, functional ability can be optimized. PT remains one of the few interventions capable of improving day-to-day life for these patients.

Parting Words

MSA challenges even experienced clinicians, especially when early symptoms mimic severe PD or when autonomic dysfunction overshadows motor symptoms. But with early recognition, consistent monitoring, and thoughtful intervention, physical therapists can profoundly impact safety, independence, and quality of life. Our expertise in autonomic monitoring, mobility progression, caregiver education, orthotic and equipment prescription, and functional restoration places us at the center of interdisciplinary care for individuals with MSA.

References

1. Raccagni C, Goebel G, Gaßner H, et al. Physiotherapy improves motor function in patients with the Parkinson variant of multiple system atrophy: A prospective trial. Parkinsonism Relat Disord. 2019;67:60-65. doi:10.1016/j.parkreldis.2019.09.026

2. American Parkinson Disease Association. Planning for the What-Ifs – Multiple System Atrophy. Published January 5, 2021. Accessed December 7, 2025. https://www.apdaparkinson.org/article/planning-for-the-what-ifs-multiple-system-atrophy/

3. Coon EA, Ahlskog JE. My Treatment Approach to Multiple System Atrophy. Mayo Clin Proc. 2021;96(3):708-719. doi:10.1016/j.mayocp.2020.10.005

Disclaimer

I am a current Doctor of Physical Therapy (DPT) student sharing information based on my formal education and independent studies. The content presented in this newsletter is intended for informational and educational purposes only and should not be considered professional medical advice. While I strive to provide accurate and up-to-date information, my knowledge is based on my current academic and clinical rotations and ongoing learning, not extensive clinical practice.