Motor Symptoms Overview

Elena Call, MD

Movement Disorders Specialist, Kaiser Santa Clara

Editor’s Note: These are brief notes from Elizabeth Wong about what she got out of the presentation and what she learned from the Q&A.

Dr. Elena Call, a movement disorder specialist at Kaiser Santa Clara in Redwood City, provides an overview of the motoric symptoms of multiple system atrophy (MSA), how it is diagnosed, symptom management, disease progression, and future research directions.

Multiple System Atrophy (MSA) is a progressive neurodegenerative condition where a misfolded protein, alpha-synuclein, accumulates in the brain's support cells, leading to the degeneration of areas controlling movement, balance, and autonomic functions. MSA manifests primarily in two forms: MSA-P, with symptoms akin to Parkinson's disease like slowness of movement (bradykinesia), rigidity, and postural instability; and MSA-C, characterized by cerebellar dysfunction causing ataxia, which results in poor coordination and unsteady gait. However, many individuals experience a blend of these symptoms.

The motor symptoms of MSA are varied and can significantly impact daily life. Parkinsonism in MSA includes not only potential tremors but also a marked slowness of movement, muscle stiffness, reduced facial expressions, and difficulties with posture. Ataxia leads to an unsteady, wide-based walk, challenges with fine motor skills, and involuntary eye movements (nystagmus). Dystonia, involuntary muscle contractions, often affects the neck, causing abnormal and sometimes painful postures like anterocollis (forward head flexion). Swallowing and speech are frequently affected, with early swallowing difficulties being a key indicator for MSA. Speech can become slurred, quiet, or have an altered rhythm. Gait disturbances are common, including feeling off-balance, shuffling, freezing, and difficulty turning. Involuntary movements (dyskinesias) can also occur as a side effect of some medications.

Diagnosing MSA is a complex process that involves a thorough neurological examination, a review of the individual's symptoms and their progression, and brain imaging, particularly MRI, which can reveal characteristic signs. While there is no cure, management focuses on alleviating symptoms and maintaining function through exercise, physical, occupational, and speech therapies. Medications can help manage some symptoms, though their effectiveness can vary. MSA typically progresses over several years, leading to increasing disability. Ongoing research into the underlying causes and potential treatments offers hope for improved diagnostics and therapies in the future.

Now onto the notes,

Elizabeth

“Multiple System Atrophy: A Focus on Motor Symptoms”

Presented during Multiple System Atrophy Symposium

Speaker: Elena Call, MD, Movement Disorder Specialist

Symposium Host: Brain Support Network and Stanford Movement Disorder Clinic

Symposium Date: May 4, 2024

Summary by: Elizabeth Wong, Stanford Parkinson’s Community Outreach

Overview of Multiple System Atrophy (MSA)

MSA is a progressive neurodegenerative condition characterized by various symptoms. While the focus of this talk is on motor symptoms, MSA also involves:

Parkinsonism: Features resembling Parkinson's disease.
Ataxia: Lack of coordination.
Autonomic Derangements: Problems with involuntary bodily functions.
Cognitive and Psychiatric Symptoms: Changes in thinking and behavior.

Pathologically, MSA involves the misfolding and accumulation of alpha-synuclein protein. This accumulation occurs predominantly in the cytoplasm of support cells around neurons called oligodendrocytes, rather than in the neurons themselves. The affected brain regions include:

Striatonigral Systems: Involved in movement control.
Cerebellum: Responsible for balance and coordination.
Pons and Olives: Structures in the brainstem crucial for various functions.

MSA affects an estimated 15,000 to 50,000 Americans, with roughly equal prevalence in men and women. The typical age of onset is in the fifth or sixth decade of life, although it can occur as early as the 30s. The average disease progression is six to ten years.

There are two main clinical phenotypes of MSA that correlate with pathological findings:

MSA-P (Parkinsonism Predominant): Characterized primarily by parkinsonian symptoms. Gross pathology shows atrophy predominantly in the striatum.
MSA-C (Cerebellar Predominant): Characterized primarily by cerebellar symptoms. Gross pathology reveals marked atrophy of the cerebellum and pons.

Motor Symptoms of MSA

A wide range of motor symptoms can occur in MSA, and not all patients experience the same manifestations.

Parkinsonism is a key feature of MSA-P and includes:

Bradykinesia: Slowness of movement, affecting overall motor activity and specific tasks like finger tapping.
Rigidity: Increased muscle tone that is present regardless of the speed of movement, making limbs feel stiff and difficult to move.
Tremor: While tremor can occur, the classic pill-rolling tremor seen in Parkinson's disease is less common in MSA.
Parkinsonism can manifest as resting tremors, slowness of movements (bradykinesia), rigidity, reduced facial expression (appearing less animated or even "mad"), and changes in posture such as bending forward or tilting.

Ataxia is more prevalent in MSA-C but can be seen in any MSA patient. It is defined as incoordination that can affect:

Gait: Leading to an unsteady, wide-based walk.
Fine Motor Movements: Difficulty with tasks requiring precise hand movements. Incoordination or tremors in the hands during movement
An observer might also notice nystagmus, involuntary eye movements

Dystonia involves involuntary abnormal posturing. In MSA, it most commonly affects the neck, leading to:

Anterocollis: Involuntary flexion of the neck forward, which can cause pain and difficulties with eating, swallowing, and speech.
Other possible neck postures include torticollis (head turning), laterocollis (lateral neck flexion), and retrocollis (neck extension).
Treatment with Botox® injections can be attempted but is often challenging due to the risk of affecting swallowing muscles.

Swallowing Dysfunction (Dysphagia) is a significant concern in MSA. Early onset of swallowing difficulties (within the first three years) is a red flag that distinguishes MSA from typical Parkinson's disease. Symptoms can range from mild difficulties with pills or secretions to more severe choking or aspiration. The complex coordination of 20-30 muscles involved in swallowing can be disrupted. Collaboration with speech therapists is crucial for managing dysphagia.

Speech Changes (Dysarthria) can occur in various ways in MSA, including:

Slurring of Speech: Making it difficult to understand the patient.
Reduced Speech Volume: Speaking softly.
Raspiness of Voice.
Loss of Prosody: Reduced emotional inflection in speech.
Changes in Pitch.
In cerebellar predominant MSA, speech may become scanning, characterized by abnormal pauses.

Laryngeal stridor is a high-pitched inspiratory noise caused by the adductor muscles of the larynx being stronger than the abductors. This can occur during sleep or wakefulness and carries a worse prognosis if not identified and managed. Referral to an ear, nose, and throat (ENT) specialist and sleep studies may be necessary.
Posture Changes: Abnormal postures are common in MSA, including:

Stooped Posture: Bending forward.
Tilting to One Side. Physical therapy is important for addressing postural issues.

Gait Disturbance
Walking difficulties are a frequent complaint in MSA. Manifestations can vary greatly and include:

Feeling Off Balance or Unsteady.
Dragging a Leg.
Difficulty Initiating Gait (Akinesia).
Freezing of Gait: Sudden inability to move while walking.
Wide-Based (Ataxic) Gait.
Scuffing the Feet.
Decreased Stride Length.
Difficulty with Turns (En Bloc Turning): Requiring multiple steps to turn.

Dyskinesia is involuntary movements that can occur with exposure to dopaminergic medications like carbidopa-levodopa (Sinemet®). In MSA, they are most common in the mouth but can occur in any part of the body.

Clinical Diagnosis of MSA

Diagnosing MSA is complex and currently relies on expert consensus criteria developed by the International Movement Disorder Society. These criteria consider different levels of diagnostic certainty. The most stringent criteria for a "probable" diagnosis in living patients include:

Age over 30 years.
Sporadic occurrence, no better explanation for the symptoms.
Evidence of autonomic failure (urinary retention, urgency/incontinence, or orthostatic hypotension).
Presence of either poorly levodopa-responsive parkinsonism or a cerebellar phenotype
2 clinical markers/features
1 MRI marker

Red Flags Suggesting MSA
Certain clinical features raise suspicion for MSA in patients presenting with parkinsonism or cerebellar symptoms:

Rapid progression of symptoms (within the first three years).
Early falls.
Early and significant imbalance.
Moderate to severe speech or swallowing problems early in the disease course (within 3 years of onset)
Development of anterocollis.
Upgoing toes (Babinski sign), indicating hyperreflexia.
Polyminimyoclonus: Jerky, fine finger movements when hands are outstretched.
Jerky tremor during finger-to-nose testing.
Non-motor stridor or inspiratory sighs.
Extreme discoloration of hands and feet (related to dysautonomia).
Erectile dysfunction (as part of a broader symptom complex).
Emotional incontinence ( sudden, uncontrollable outbursts of crying or laughing that are often out of proportion to the situation or the person's actual emotional state).

Specific MRI findings can support the diagnosis of MSA:

Hot Cross Bun Sign: A cruciform hyperintensity seen on T2-weighted MRI in the pons, indicating degeneration of cerebellar-pontine connections.
Cerebellar Atrophy: Shrinkage of the cerebellum.
Pons Atrophy: Flattening or reduction in size of the pons.
Putaminal Rim: Hyperintense rim around the putamen on T2-weighted MRI, indicating degeneration.

Adjunctive Tests
While clinical evaluation and MRI are primary, adjunctive tests may be used in cases of diagnostic uncertainty:

DAT Scan: A nuclear medicine scan that assesses dopamine transporter levels. It is abnormal in Parkinson's disease and other synucleinopathies but does not specifically diagnose MSA. It can help differentiate from cerebellar patients who have spinocerebellar ataxia vs MSA.
PET Scan: Can show patterns of glucose metabolism in the brain that may differ between degenerative diseases, but is not routinely used for MSA diagnosis.
CSF Biomarkers and Skin Tests: Emerging tests looking for alpha-synuclein may play a larger role in diagnosis in the future.

Management of Motor Symptoms

Management focuses on symptomatic relief and maintaining function.

Aerobic exercise is crucial for slowing disease progression and maintaining physical function. Aim for at least 30 minutes daily at an intensity appropriate for the individual's disease stage. Examples include brisk walking (early stages), stationary biking, and pedal machines (later stages). Exercise also promotes social engagement.

Physical, Occupational, and Speech Therapists are essential members of the care team.

Physical Therapy (PT): Focuses on gait, balance, posture, home exercise programs, safe use of assistive devices, techniques for managing freezing of gait, and safe transfers.
Occupational Therapy (OT): Aims to maximize independence and function in daily activities such as dressing, showering, toileting, cooking, and eating. OT considers individual strengths, environmental modifications, and adaptive equipment. They also address fine motor skills and hobbies.
Speech Therapy (ST): Addresses changes in voice (volume, clarity, prosody), swallowing difficulties (techniques for safe swallowing, dietary modifications), and cognition. ST can also help with adaptive communication technologies (e.g., Tobii Dynavox®) and alternative communication methods as the disease progresses.

Medications

Carbidopa-Levodopa (Sinemet®): Dopaminergic therapy that can be tried, especially in MSA-P, to improve parkinsonian symptoms. Effectiveness varies, and side effects like lightheadedness, low blood pressure, fatigue, confusion, hallucinations, and nausea can occur. Dyskinesias, particularly oral dyskinesias, are common. It tends to become less effective as the disease progresses.
Amantadine: An anti-dyskinetic medication that may be used to manage dyskinesias.
Botox® Injections: May be attempted for anterocollis, although results can be challenging, and caution is needed to avoid affecting swallowing muscles.
Muscle Relaxants: May be used for spasticity or spasms, balancing the benefits against potential sedation and increased fall risk.
Addressing Vitamin Deficiencies: Ensuring no underlying vitamin deficiencies (e.g., Vitamin E, B12) are contributing to symptoms.

Disease Progression

MSA typically progresses gradually over a period of six to ten years.

Prodromal Phase: May involve non-motor symptoms like loss of smell, REM behavior disorder, and constipation.
Early Stages: Characterized by mild parkinsonism or cerebellar features.
Progression: Leads to increasing motor impairments, falls, speech and voice changes, and swallowing problems.
Late Stages: Severe orthostatic hypotension becomes more prominent, speech may worsen significantly, and increased reliance on family or assisted living care is common.

Future Directions in Research

Current disease-modifying therapy trials for MSA have been largely negative. However, promising research avenues include:

Ubiquinol (CoQ10): A small phase three trial suggested potential benefit.
Anti-Sense Oligonucleotides: Very early-stage research.
Immunotherapies (Monoclonal Antibodies to Alpha-Synuclein): In phase two trials.
Stem Cells: An area of ongoing investigation.
Early Diagnosis and Biomarkers: Advances in identifying MSA in the prodromal phase and developing reliable diagnostic biomarkers (e.g., from skin, CSF, or blood using alpha-synuclein seed amplification assays) hold significant hope for future research and treatment development.

Questions and Answers

Q: Is Pisa syndrome more common in MSA than in Parkinson’s disease?

A: I don’t know, postural problems, including Pisa syndrome (lateral trunk flexion), are generally more likely to be seen sooner in MSA compared to Parkinson's disease, although Parkinson's is a more common condition overall.

Q: Do you have problems with getting insurance approvals for PT/OT/ST for chronic conditions?

A: I am glad I work at Kaiser because all of our services are in house.

Q: For those locally with Kaiser, would you recommend we ask for a referral to see you?

A: I am one of nine movement disorder specialists in the entire Kaiser Northern California region. Individuals with suspected or diagnosed MSA within the Kaiser Northern California system were encouraged to seek referrals to regional movement disorder specialists.

[If anybody is in the Northern or Central California and needs referral outside of Kaiser, contact the American Parkinson Disease Association (ADPA) Information & Referral Center at Stanford University]

Q: At what point in progression would MRI be used to confirm diagnosis of MSA?

A: MRI of the brain is typically performed early in the evaluation of parkinsonism or cerebellar symptoms. While initial MRIs may be normal, characteristic signs of MSA (e.g., hot cross bun sign, cerebellar/pons atrophy, putaminal rim) may develop over time. MRI findings are considered along with clinical features and diagnostic criteria. For many people in the first three years of presentation, there may not be enough to make a diagnosis so that leads to a lot of grief for some people. For example, it may not be clear if its PSP, or corticobasal syndrome, or MSA, or even dementia with lewy body, sometimes it's really obvious, and sometimes people can have features of all of those conditions, and diagnosis cannot be made, but it will become more clear over time. DAT scans can be helpful in certain situations to differentiate diagnostic possibilities but have limitations and potential for false positives or negatives.

Q: What is “Emotional Incontinence”?

A: This refers to the inability to control emotional expression, often manifesting as crying or laughing without a corresponding feeling of sadness or happiness (similar to pseudobulbar affect).

Q: My husband was diagnosed in 2009 and seems to be slowly progressing MSA, should I get a second opinion?

A: While MSA typically progresses over 6-10 years, a significantly longer course is unusual, warranting consideration of a second opinion to ensure the accuracy of the diagnosis.

Q: How would you treat excessive saliva (Sialorrhea):

A: Options include atropine drops under the tongue, glycopyrrolate (oral), and Botox® (Myobloc®) injections into the salivary glands for more severe cases.