Multiple System Atrophy

Original Editors - Emily Nicklies from Bellarmine University's Pathophysiology of Complex Patient Problems project.

Top Contributors - Emily Nicklies, Lucinda hampton, Admin, Kim Jackson, Dave Pariser, Wendy Walker, Naomi O'Reilly, WikiSysop, Amrita Patro and Elaine Lonnemann  

Introduction

Multiple System Atrophy (MSA) is defined as a sporadic, fatal, progressive, neurodegenerative adult-onset disorder. It is the second most common neurodegenerative movement disorder with an average annual incidence rate of 3 per 100000 person-years after Parkinson’s disease (PD). It can affect the

• Autonomic system causing autonomic failure, causing eg.fainting spells and problems with heart rate, erectile dysfunction, and bladder control.
• Basal ganglia causing parkinsonism, causing eg tremor, rigidity, and/or loss of muscle coordination as well as difficulties with speech and gait.
• Cerebellum causing ataxia

The symptoms reflect the progressive loss of function and death of different types of nerve cells in the brain and spinal cord.

Some of these features are similar to those seen in Parkinson’s disease, and early in the disease course it often may be difficult to distinguish these disorders. The 2 minute video below gives a good introduction to MSA

Etiology

The causes of MSA are unknown; however, as for other neurodegenerative diseases, a complex interaction of genetic and environmental mechanisms seems likely.
Research has suggested that MSA is characterized by a progressive loss of neuronal and oligodendroglial cells (myelin producing cells in CNS) in numerous sites in the CNS (basal ganglia, cerebellum). This damage is said to occur from the formation of glial cytoplasmic inclusions (GCI’s).

Epidemiology

MSA is an orphan disease with an incidence of up to 2.4 cases per 100 000 persons per year, while the prevalence may reach up to 7.8 patients per 100 000 population over the age of 40. The MSA‐P variant seems to be more common in the western hemisphere, whereas MSA‐C appears to be more frequent in Asia .

There is about 1 living case of MSA in the population for every 40 cases of Parkinson’s disease, but because survival in MSA is shorter than for PD, about 1 new MSA case presents every year for about every 20 who present with PD.

Symptoms

The symptoms reflect the progressive loss of function and death of different types of nerve cells in the brain and spinal cord. The initial symptoms of MSA are often difficult to distinguish from the initial symptoms of Parkinson’s disease and include: slowness of movement, tremor, or rigidity (stiffness); clumsiness or incoordination; impaired speech, a croaky, quivering voice; fainting or lightheadedness due to orthostatic hypotension; bladder control problems, such as a sudden urge to urinate or difficulty emptying the bladder.

Classification

MSA is classified by the most dominant symptom exhibited by the patient.

1. Parkinsonian type (MSA-P): this includes symptoms similar to Parkinson's disease eg tremors at rest, rigidity of muscles, and slow movements, including gait
2. Cerebellar type (MSA-C): involves difficulty walking (ataxia), issues maintaining balance, and trouble coordinating voluntary movements.

Cognition

Cognitive deficits occur in all cognitive domains. The impaired cognitive domains had a significant correlation with atrophy of frontotemporal cortical areas, insula, caudate, thalamus, and cerebellum. Impaired cognition is due to the pathology in both cortical and subcortical structures. Cognitive impairment, particularly seen in executive function, may occur in up to 75% of patients The Mini-Mental State Examination, or MMSE, yielded 3% of participants showing signs of cognitive decline while a test called the Frontal Assessment Battery (FAB) categorized 41% of participants as being cognitively impaired. The FAB is a cognitive test that incorporates several clinical assessments to screen for frontotemporal dementia (FTD)

• Emotional instability may occur later in the progression of the disease
• Depression, anxiety, panic attacks, and suicidal ideation may present in MSA
• Patients with MSA can have great difficulty switching attention from one stimulus to another, with a decrease in goal-oriented cognitive ability.

Diagnosis

At this time, there are no specific symptoms, blood tests or imaging studies that distinguish MSA. It can take a while to receive an MSA diagnosis because of the similarities between MSA and other conditions, eg Parkinson's disease. MSA is usually diagnosed around 50 years of age and is seen in people of all ethnic backgrounds. Once symptoms begin, the disease tends to progress quite rapidly.

The Mini-Mental State Examination, or MMSE, yielded 3% of participants showing signs of cognitive decline while a test called the Frontal Assessment Battery (FAB) categorized 41% of participants as being cognitively impaired. The FAB is a cognitive test that incorporates several clinical assessments to screen for frontotemporal dementia (FTD),

Diagnostic Challenge

There is no “typical” presentation for this disorder, and MSA can often be masked by other diagnoses.

• Patients with MSA are most commonly misdiagnosed with Parkinson’s Disease. About 1/3 of people with MSA die while still misdiagnosed.
• Only 25% of patients with MSA are correctly diagnosed at their first neurological visit. The correct diagnosis is usually established on an average of 4 to 5 years after the disease onset.

Management

Currently, there is no cure for MSA, nor are there any treatments specifically designed to reverse or stop disease progression.

• Movement disorders can be treated with levodopa and carbidopa (Sinemet), but this usually has limited results.
• Other medications such as trihexyphenidyl (Artane), benztropine mesylate (Cogentin), and amantadine (Symmetrel), may also offer some symptom relief. Several medications exist to treat orthostatic hypertension (drop of the blood pressure when standing up)—fludrocortisone midodrine, and droxidopa.
• Physical and occupational therapy, eg aqua therapy, can help maintain muscle function, and speech therapy can help improve any difficulties swallowing or speaking.

Physical Therapy Management

Physical therapies offer drug-free tools for keeping muscles strong and flexible, helping prevent falls and other incidents that hasten disability. Encouraging mobility also lowers the risk of pulmonary embolism which can be fatal.

There is very little published literature on physical therapy or exercise intervention for patients with MSA.
There is the most evidence concerning patients with MSA-A.

Since majority of patients with MSA-A seem to experience orthostatic hypotension (OH), this is a main focus during a treatment session. For effective strategies for OH see link.

Bowel and Bladder Treatment:

• Begin a urinary incontinence program if appropriate.  Introducing exercises for the pelvic floor musculature in order to gain control/suppress urge, etc.

Gait/Mobility Training:

• Fit the patient for the most appropriate assistive device in order to gain independent mobility.  This will depend upon the patient’s level of function and safety.
• If a wheelchair is most appropriate, ensure the chair is one that will best benefit their posture and mobility based upon the function of patient. 
• As a PT, the need to promote independent functional mobility and optimal posture with safety in mind is most important.

Therapeutic Exercise/Activities:

• According to a study by Wedge, et al., gait training, transfer training, balance activities, and conditioning are necessary in reaching the goal of minimizing fatigue and risk for falling (safe transfers, etc.)
• Resistance training has been proven to be effective in patients with MSA.
  • Knee extensors and flexors, hip abductors and adductors, and ankle plantarflexors were targeted for resistance training.  These muscle groups are chosen because of their importance to balance.
  • Following resistance training interventions, marked improvements are noted in the patient's gait pattern (increased consistency in maintaining good step height and length even when fatigued).  Reduces festinating gait and other functional changes achieved.  The patients improve transfer technique and posture (ie good head and trunk alignment in both sitting and standing). Also less frequency of falling.

Additional Physical Therapy Advice:

Research reinforces the fact that since MSA is a variable disorder.  Each patient with MSA will present differently, so it is difficult to give clear PT advice.

• Based upon a patient’s level of mobility and function, PT's should use their skills and knowledge to promote a safe and optimal environment for the patient.
• As a PT, maintaining strength and physiologic fitness as long as possible will be most valuable to the patient.
• Education of the patient and family on benefits of PT is important for patient/family knowledge and compliance.
• Make PT goals realistic.  Base the goals upon current function and take into consideration the activities most important to the patient. 
• Since this is a progressive disorder, PT's must make sure to re-evaluate goals often to make sure they are appropriate.

Differential Diagnosis

MSA often presents as the following disorders:

• Pure Parkinsonism,,,
• Pure Autonomic Failure (PAF),,,
• Progressive Supranuclear Palsy
• Corticobasal Ganglionic Degeneration

Prognosis and Outlook

Prognosis is currently guarded, with most MSA patients passing away from the disease or its complications within 6-10 years after the onset of symptoms. Nonetheless, there is reason for hope for MSA research goes on. Since the biology of MSA may be related to other neurodegenerative diseases like Parkinson's disease, it is possible that therapies designed for other conditions will also prove helpful for patients with MSA.

Case Reports

Wedge F. The Impact of Resistance Training on Balance and Functional Ability of a Patient with Multiple System Atrophy. Journal of Geriatric Physical Therapy 2008;31:79-83.
The following case report documents the impact of a resistance-training program on a 68 year-old-female patient with a 2-year history of MSA. 

Hemingway J, Franco K, Chmelik E. Shy-Drager Syndrome: Multisystem Atrophy With Comorbid Depression. Psychosomatics. 2005;46:73-6.

The following case report discusses the some of the struggles in the diagnostic process of a 48 year old man with MSA.  

Mashidori T, Yamanishi T, Yoshida K, Sakakibara R ,Sakurai K, Hirata K. Continuous Urinary Incontinence Presenting as the Initial Symptoms Demonstrating Acontractile Detrusor and Intrinsic Sphincter Deficiency in Multiple System Atrophy. International Journal of Urology. 2007;14:972-74.
The following case report demonstrates how urinary incontinence can be the first symptoms of MSA in a 66-year-old female.

Goto K, Ueki A, Shimode H, Shinjo H, Miwa C, Morita, Y. Depression in Multiple System Atrophy: A Case Report. Psychiatry and Clinical Neurosciences. 2000;54:507-11. The following case report demonstrates how depression can be the first symptoms of MSA in a 56-year-old female. 

Resources

SDS/MSA Support Group

http://www.shy-drager.org/