The Challenge of MSA: Multiple System Atrophy

Submitted by Margo Quinlan, RN, MSN

Tags: challenge diagnosis MSA multiple system atrophy neurologist

The Challenge of MSA: Multiple System Atrophy

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Written at Laboure College, Boston, MA

I visit my brother Jack four to five times a year. After a recent visit I asked my husband if he noticed that Jack seemed very quiet, distant and had little to add to the conversation. Jack’s affect was flat. I thought he might be depressed since he had recently retired and there had been a death in the family. Four months later Jack was diagnosed with Parkinson’s Disease (PD) by his primary physician and started on Sinemet. I was surprised since he didn’t have tremors, but his walk was slower.

Five months later his wife called and said “Jack has been diagnosed with MSA and there’s not much they can do.” I asked if she meant MRSA. “No, it’s like Parkinson’s but there’s no known medication that helps.” The diagnosis was made by a neurologist who specializes in multiple system atrophy (MSA).
 
As time passed, Jack’s staring expression (mask-like fascies) became more evident. Difficulty with balance and walking progressed quickly, and he developed a wide stance as a compensatory measure for “freezing”. Jack was never troubled with tremors, but his generalized bradykinesia and stiffness were noticeable. Despite the physical therapy and safety precautions that were instituted, his hupotensive episodes and falls were more numerous. As the months progressed his hoarseness, hypophonia and dysarthria became troublesome. Jack’s speech was difficult for the family and caregivers to understand and frustrating for Jack. Toward the end of this battle with MSA he had difficulty in swallowing, which led to aspiration pneumonia several times. His breathing was stridorous and he required frequent suctioning. Thanks to his family’s support and the wonderful care by Hospice, he died quietly in his sleep from pneumonia.

In the early 1960’s, two doctors from Texas recognized that clinical manifestations of parkinsonism, in conjunction with, autonomic dysfunction was a unique entity, and called it Shy-Drager’s, now referred to as MSA.

MSA is a heterogeneous neurodegenerative disorder with clinical presentation of extrapyradmidal, cerebellar, autonomic or pyramidal symptoms. There are two major subtypes:
MSA-P is primarily caused by degeneration of the striatonigral pathways with a clinical predominance of bradykinesia, rigidity, stiffness and postural imbalance.
MSA-C manifests a predominance of cerebellar symptoms. due to atrophy of the cerebellum, olives and pons This is evidenced by ataxia,, lack of coordination and loss of balance.1

Autonomic dysfunction is the outstanding, defining feature of MSA and is present in both types. The autonomic nervous system is composed of two major divisions; sympathetic nervous system ( SNS) and parasympathetic nervous system(PNS) which oppose, yet balance each other to maintain the body’s equilibrium. Clinical signs vary in terms of areas of the body involved, severity and rapidity of progression. The most frequent signs in MSA are: urinary dysfunction, impotence, orthostatic hypotension, respiratory, gastrointestinal and sleep abnormalities.2

“Definite MSA requires neuropathologic demonstration of CNS alpha-synuclein-positive glial cytoplasmic inclusions with neurodegenerative changes in striatonigral or olivopontocerebellar structure. Probable MSA requires a sporadic, progressive adult onset disorder including rigorously defined autonomic failure and poorly levodopa-responsive parkinsonism or cerebellar ataxia. Possible MSA requires a sporadic, progressive adult onset disease including parkinsonism or cerebellar ataxia and at least one feature suggesting autonomic dysfunction plus, one other feature that may be a clinical or neuroimaging abnormality”

What actually causes MSA?

A misprocessed protein, alpha-synuclein-positive, is present in the oligodendrocytes cells. It is known as glial cytoplasmic inclusions (GCI) and interferes with the normal production of the myelin sheath, a protective layer around the axons.1 No known treatment prevents or slows the progression of MSA, which is usually faster than idiopathic Parkinson’s. 1

What is the incidence and risk for MSA?

Many cases go undetected but MSA is thought to affect approximately 4-5 people per 100,000, primarily 50-60 years old. The incidence is slightly greater in males. The average duration of the illness is 6 years with a range of 4-15 years. The only risk factor is age, as it seldom occurs under 40 years of age. There is no data to support a predisposition due to genetic or environmental factors, though gene research is being explored.3

Diagnosis

A comprehensive physical exam and review of the clinical course of the illness is crucial to accurate diagnosis. A very distinguishing feature between PD and MSA is in PD one exhibits a tremor that is very noticeable at rest. However, in MSA there is little or no tremor and it is more pronounced during voluntary motor activities e.g. lifting an object. Sinemet relieves symptoms of PD, but has minimal if any effect in MSA.1

Diagnostic tests
 
Evaluation of blood pressure (BP) is measured in both arms. Have the patient supine for 3-5 minutes. Using the arm with the higher PB, take the VS every minute for the first 3 minutes while the patient is supine, sitting and standing. If the SBP drops more than 20 mmHg or DBP more than 10 mmHg, it is considered orthostatic hypotension (OH). Document the patient’s subjective symptoms and heart rate. A tilt table may be used for patients who experience imbalance. The patient is safely strapped on a motorized table. The vital signs are measured continuously while the table is tilted upward to vertical position as tolerated.4

MRI and CT scans assist in ruling out neurological diagnoses e.g. tumors, infarcts, NPH(normal-pressure hydrocephalus) etc. and aid in determining the progression of MSA. In MSA-P abnormal signals are in the putamen, a cluster of cells deep in the brain that regulates movement. In MSA-C there is atrophy of the cerebellum and brainstem.1,5. In 63% of MSA cases the pons-T2 weighted MRI reveals the “Hot cross bun sign”, a cruciform hyperintensity.6

PET with fluorodeoxyglucose helps in determining the presence of MSA. It may detect glial intraneuronal cytoplasmic nuclei inclusion bodies, however it is seldom used because it’s very expensive and not readily available.1
 
“The cerebral spinal fluid (CSF) neurofilament light chain and tau tests have been reported to differentiate MSA from PD but remain in an exploratory phase of development.”1

Based on clinical manifestations other tests e..g. urology, sleep and swallow studies may be ordered The only definitive test is autopsy brain cell biopsy showing evidence of alpha-synuclein protein.
 
The role of the nursing is critical in maintaining the patient’s quality of life, potentiating capabilities and preventing complications. “The most common signs in pathologically confirmed cases of MSA are: parkinsonism 87%, autonomic dysfunction 74%, cerebellar ataxia 54% and pyramidal signs 49%:”.2
Potential for injury R/T orthostatic hypotension (OH)

A comprehensive nursing assessment is key to identifying causative factors and instituting specific measures to remedy OH e.g. timing of medications, particularly anti-hypertensives and antidepressants. Symptoms of hypotension can vary from mild fatigue, slowing of thought processes, the inability to participate in ADL’s to falling and sustaining life-threatening injuries. Fatigue and light-headedness may make the patient feel uncertain, fearful, depressed and become socially isolated. Monitoring for supine hypertension is crucial when a patient is receiving meds for hypotension

Vasodilatation, due to prolonged standing, intense physical exertion, rise in environmental and/or body temperature, causes an increased risk for OH.
The autonomic dysfunction inhibits the normal response of vasoconstriction to maintain the blood pressure. Inadequate vascular volume also compounds hypotension. Post-prandial hypotension occurs because the splanchnic-mesenteric vascular bed, is unable to compensate and re-establish equilibrium. The splanchnic-mesenteric bed contains 25-30% of the body’s total blood volume.4

Orthostatic hypotension is managed primarily by patient teaching and medications. Patient compliance is the way to success.
Patient teaching includes the following: Eat small, frequent meals, minimize simple sugars and no ETOH.

Increase fluids and salt to maintain blood volume. Caffeine may be helpful in the AM
Perform pedal-pushes, leg-crossing and thigh contraction exercises
4-5 times daily. Swimming is excellent because isotonic exercises
produce less hypotension than isometric.

Wear elastic thigh stockings and/or abdominal support when out of bed

Raise the head of the bed with 4-6” blocks at night to reduce the potential effects of supine hypertension. The upright position diminishes the effect of supine HTN by reducing press-natriuresis in the kidney and increases rennin secretion, thereby restoring vascular volume.5
These rather simple, but effective strategies enhance the safety of the patient. Patients need continuing support and encouragement to adapt these new interventions into their daily routine.

Commonly used medications

Midodrine (ProAmatine) is usually the initial drug of choice. It’s an oral selective a-1 agonist which is effective within an hour, lasting 2-4 hours. Since it has the tendency to raise the supine BP, it should be taken early in the morning, 1 hour before arising, when the BP is naturally lower. The patient should take Midrodrine with plenty of water and remain in bed for 30-60 minutes. Additional doses may be taken before lunch and in the early afternoon. Midrodrine should never be taken after 6PM. Midodrine increases sphincter tone therefore urinary retention should be carefully monitored. The majority of patients benefitted from 10 mg of the medication.4
 
Pyridostigmine (Mestinon), a cholinterase inhibitor, acts by improving the ganglionic transmission, effectively increasing the standing BP with minimal effect on supine BP. The usual dose is 30 mg 2-3 times daily. The main side effect is abdominal colic.

Fludrocortisone (Florinef) retains salt and water, thus expanding plasma volume which raises the BP. At high doses, hypokalemia, hypernatremia and supine HTN may increase. It takes about 4-5 days to reach full effect and may be used in conjunction with midodrine.4

Cognition is affected in only a small percent of cases.1 Throughout the course of the illness patients should be encouraged to participate in all decisions concerning their health. Patient and family may benefit by participating in local and national support groups. They provide the opportunity to share ideas on ways to manage the physical, psycho-social, and financial aspects of this complex disease.
The medical interdisciplinary health team plays a critical role in assisting the patient and caregivers in the discussion of end-of-life issues. As the disease progresses the struggle to make choices is an on-going process. The primary care giver is the spouse in the vast majority of cases and needs to be aware of what is driving their choices. Hospice is an excellent resource for all involved, both during and following the illness. The chaplain may be able to help individuals recognize the difference between giving up and letting go. Learning to live encompasses the ability to let go. It is an acceptance of our mortality and humanity. MSA is definitely a very demanding, challenging and life-shortening disorder.

Jack and his immediate family were fortunate in being able to address advance directives together. He was very spiritual and his religious faith played a major role in his ability to accept the challenge of living and dying with MSA. He selected Hospice and comfort measures were instituted in the nursing home. Increased respiratory secretions and the inability to cough effectively required frequent suctioning. Jack’s restlessness and discomfort were relieved by IV morphine and he died peacefully with his family present.

Support groups

The SDS/MSA Support Group. 2004 Howard Lane, Austin, TX.78728
(1-800-288-5582).
http://www.Shy-drager.com
American Academy of Neurology, 1080 Montreal Ave., St.Paul, MN 55116-612-695-1940. http://www.rarediseases.org
Anatomic Dysfunction Center, Vanderbilt University Medical Center.
Nashville, TN 37232-2195. Phone:615-343-8649.

Cognition is affected in only a small percent of cases.1 Throughout the course of the illness patients should be encouraged to participate in all decisions concerning their health. Patient and family may benefit by participating in local and national support groups. They provide the opportunity to share ideas on ways to manage the physical, psycho-social, and financial aspects of this complex disease.

The medical interdisciplinary health team plays a critical role in assisting the patient and caregivers in the discussion of end-of-life issues. As the disease progresses the struggle to make choices is an on-going process. The primary care giver is the spouse in the vast majority of cases and needs to be aware of what is driving their choices. Hospice is an excellent resource for all involved, both during and following the illness. The chaplain may be able to help individuals recognize the difference between giving up and letting go. Learning to live encompasses the ability to let go. It is an acceptance of our mortality and humanity. MSA is definitely a very demanding, challenging and life-shortening disorder.

Jack and his immediate family were fortunate in being able to address advance directives together. He was very spiritual and his religious faith played a major role in his ability to accept the challenge of living and dying with MSA. He selected Hospice and comfort measures were instituted in the nursing home. Increased respiratory secretions and the inability to cough effectively required frequent suctioning. Jack’s restlessness and discomfort were relieved by IV morphine and he died peacefully with his family present.

References

  1.  Gilman S, Wenning GK, et.al. Second consensus statement on the diagnosis of multiple system atrophy. Neurology. 2008;71(9):670-76.
  2.  Bradley WG, Daroff, RB, Fenichel GM, Jankovic J. eds. Neurology in Clinical Practice. (4th ed), 2004. Philadelphia, Pa: Butterworth-Heinemann/Elsevier).
  3. Shlossmacher M, Hamann C, Cole A, et.al. A 79 year-old woman with disturbances in gait, cognition and autonomic function. New England Journal of Medicine. 2004;351(9):912-922.
  4.  Low PA, Singer W. Up date on management of neurogenic orthostatic hypotension. Lancet Neurology. 2008;7(5):451-58.
  5. Olanow CW, Stern MB, Serbi K. The scientific and clinical basis for the treatment of Parkinson disease. Neurology. 2009;72(Suppl 4):S6,S80-33.
  6.  Lee Y-C, Liu CS, et.al. The ‘hot cross bun’ sign in the patients with spinocerebellar ataxia. Eurpean .Journal of Neurology. 2009;16(4):513-16.
  7.  Van de Warrenburg BP, Bhati KP, Quin NP. Causes of death in multiple system atrophy. Journal of neurosurgery-psychiatry. 2001;78(3):327-29.
  8. Pavior DC, Williams D, et.al. Is sphincter electromyography helpful in the diagnosis of multiple system atrophy? Mov. Disord. 2005;20(11):1425-30.
  9. Iranzo A, Santamaria J, Tolosa E. The clinical and pathophysiologic relevance of REM sleep behavior disorder in neurodeenerative diseases.
    Sleep Medical Review. 2009;April 8.(pre pub on internet)
  10. Sachin S, Shukla G. Clinical speech impairment in Parkinson’s disease, progressive supranuclear palsy, and multiple system atrophy. Neurology India. 2008;56:122-26.

Review of the brains’s anatomy

Cerebrum, the largest area of the brain, is located above the brain stem. It has 2 hemispheres, right and left, which are divided into lobes, each having a particular function.

The frontal lobe plays an important role in developing of one’s reasoning, decision making skills, intelligence, memory, behavior and personality. The left frontal lobe, known as Broca’s area, coordinates speech muscles and major body movements.

The temporal lobes in the lower part of the cerebrum manage most of
the auditory activities e.g. translating words into meaning. It is involved in behavior, emotions and speech development. In most right handed people the left temporal lobe controls language comprehension, thus it is called the dominant lobe.

The parietal lobes, located in the upper central area, process messages being sent to and from the lobes concerning physical sensations. It aids knowing the right from left, spatial orientation, and awareness of body parts. It facilitates one’s ability to calculate, read and write.

The occipital lobes, in the back portion of the cerebrum, process what is seen by the retinas, allowing one to judge distances and spatial
relationships. Like the temporal lobes, the right lobe processes what is seen in the left field of vision.

The cerebellum, located posterior to the brain stem, helps to coordinate movement, balance, posture and fine muscle control. Current research reveals the cerebellum may enhance one’s ability to listen to speech and music and develop greater awareness of various stimuli.

Brain stem- All functions controlled by the cerebrum pass through the brain stem which is located at the base of the brain. It is composed of 3 parts: midbrain, pons and medulla oblongata. This area controls involuntary functions: breathing, blood pressure, heart rate, and swallowing. It aids in developing sleep/wake patterns, and involuntary functions. It has 12 cranial nerves which control hearing, vision, sense of smell and balance.

The spinal cord, a continuation of the brain stem, receives and transmits sensory information and motor commands to the body via neurons. This transfer of impulses is an electro-chemical reaction which requres neuro-transmission of chemicals e.g. dopamine, acetycholine or serotonin. The axons are covered with a myelinated sheath which enhances the speed of the impulse. A neuron can receive and transmits multi impulses over a variety of pathways simultaneously. In MSA the glia cells have an abnormal protein called alpha-synctein, which interferes with the production of the myelin sheath that protects the neuron, causing dysfunction of the neuron.

The autonomic nervous system (ANS) is comprised of 2 divisions: sympathetic nervous system( SNS) and the parasympathetic nervous system (PNS). They maintain one’s dynamic equilibrium by having an opposing, but complimentary effect on the body’s organs During times of stress or emergencies, the SNS, stimulates the vital organs, e.g. heart, lungs, etc. The PNS , sometimes referred to as the “rest and digest” system because it mainly stimulates the GU, GIT and sexual function.

References

  1. Gilman S, Wenning GK, et.al. Second consensus statement on the diagnosis of multiple system atrophy. Neurology. 2008;71(9):670-76.
  2. Bradley WG, Daroff, RB, Fenichel GM, Jankovic J. eds. Neurology in Clinical Practice. (4th ed), 2004. Philadelphia, Pa: Butterworth-Heinemann/Elsevier).
  3. Shlossmacher M, Hamann C, Cole A, et.al. A 79 year-old woman with disturbances in gait, cognition and autonomic function. New England Journal of Medicine. 2004;351(9):912-922.
  4. Low PA, Singer W. Up date on management of neurogenic orthostatic hypotension. Lancet Neurology. 2008;7(5):451-58.
  5. Olanow CW, Stern MB, Serbi K. The scientific and clinical basis for the treatment of Parkinson disease. Neurology. 2009;72(Suppl 4):S6,S80-33.
  6. Lee Y-C, Liu CS, et.al. The ‘hot cross bun’ sign in the patients with spinocerebellar ataxia. Eurpean .Journal of Neurology. 2009;16(4):513-16.
  7. Van de Warrenburg BP, Bhati KP, Quin NP. Causes of death in multiple system atrophy. Journal of neurosurgery-psychiatry. 2001;78(3):327-29.
  8. Pavior DC, Williams D, et.al. Is sphincter electromyography helpful in the diagnosis of multiple system atrophy? Mov. Disord. 2005;20(11):1425-30.
  9. Iranzo A, Santamaria J, Tolosa E. The clinical and pathophysiologic relevance of REM sleep behavior disorder in neurodeenerative diseases. Sleep Medical Review. 2009;April 8.(pre pub on internet)
  10. Sachin S, Shukla G. Clinical speech impairment in Parkinson’s disease, progressive supranuclear palsy, and multiple system atrophy. Neurology India. 2008;56:122-26.

Aspiration may occurs due to autonomic dysfunction of the muscles used for swallowing and speech. Based on the speech therapist’s evaluation, which usually includes a barium swallow, diet recommendations will be made. Small, frequent feedings are used to minimize fatigue. Nutritional supplements are often needed to maintain a positive nitrogen balance. It is important to have the patient:

  • Maintain chin tuck, dry swallow 2-3 times after each mouthful
  • Eat meals in a chair or when in bed, maintain high fowler’s position
  • Remain in a sitting position 1-3H after eating/drinking
  • Drink thickened liquids, limit milk
  • Crush or use liquid meds
  • Minimize environmental distractions

As MSA advances, a repeat barium swallow may be ordered. Findings frequently indicate the need for a percutaneous gastrostomy (PEG) tube to compensate for fatigue, decreased muscle strength and weight loss. Research indicated that despite a PEG tube, patients may continue to have episodes of aspiration that lead to pneumonia.7

Jack, like many patients wanted to eat small amounts of his favorite foods. Thanks to the health team arranging the needed supervision, his wish was granted.

Ineffective airway clearance R/T muscle weakness and excess secretions

As MSA progresses, the deterioration of ANS leads to decreased muscle strength of thoracic and diaphragmatic muscles causing retention of pulmonary secretions, stridor and obstruction. Stridor is associated with a poor prognosis.7 Most common causes of death in MSA are pulmonary related; namely, apnea and recurrent infections. Mouth care before meals and at bedtime lessens the incidence of pneumonia. Increasing fluids, encouraging activity, deep breathing and expectoration of sputum is imperative. If there is any question of a respiratory infection, the patient should seek immediate medical intervention. In the terminal stages of MSA, the patient is too weak to cough up secretions and suction is required. A tracheostomy may be an appropriate option in some situations.

Alteration in mobility R/T imbalance and poor coordination

The loss of postural and righting reflexes is a reflection of the cerebellar abnormalities. They occur earlier and progress much faster in MSA than PD.2 Daily exercises will maximize and maintain the patient’s flexibility, strength, balance and coordination skills. PT plays a major role in assisting patients to attain this goal which fosters independence and a sense of well being. Patients, especially if they live alone, should have an emergency response alarm in case of falls or injury. Assistive devices e.g. hand rail, tub bar, shower chair, allow a patient to retain independence in ADL’s. A walker definitely enhances safety when a person has bradykinesia and difficulty with balance and coordination. Simple cues e.g. take small steps in a circle formation rather than pivoting or when rising from a chair, go to the edge of the chair, lean forward, and use the arms of the chair to push upward. The patient should never grasp the walker and pull himself upright. These interventions relieve some of the family’s stress and worry concerning the patient’s safety.

Alteration in elimination R/T neurogenic dysfunction

ANS deterioration affects both the genitourinary system and bowel elimination. Urological symptoms in MSA usually precede neurological by years.2 In the early stage of MSA urologic symptoms are related to detrussor muscle hyperreflexia, but later hyporeflexia predominates.2 Initial clinical manifestations are urgency and frequency. Urodynamic studies will indicate the degree of muscle tone and patient’s ability to respond to a full bladder. This allows realistic goals to be determined. Electromyography (EMG) shows that many patients with MSA have abnormal external urethral sphincter tone related to nerve degeneration.8

Fluids should be limited in the evening to decrease nocturia, which increases risk for falls. Anti-spasmodic, anti-cholinergic medications e.g. oxybutrin (Ditropan). solifenacin (Vesicare), tolterodine (Detrol LA) reduce urgency, frequency and incontinence. Urinary retention is effectively managed by catheterization, using clean technique. Catheterizing just before sleep and first thing in the morning is effective in managing severe nocturia.
 
Male impotence is an early sign of MSA and may be managed with medications e.g. Sildenafil (Viagra), tadafil (Cialis), (both PDE5 inhibitor) or Yohimbine, which is an alphas-2 adrenergic blocker. Other approaches e.g. intracavernosal papaverine injections or penile implant are seldom selected by patients.

Constipation results from impaired autonomic function, minimal physical activity, decreased fluids and dietary factors.. Patients can lessen constipation by increasing fluids (e.g. warm prune juice, coffee), fiber and exercise, particularly walking after meals and abdominal muscle strengthening exercises. Bulk-laxatives, pericolace, lactulose, or more potent laxatives may be appropriate. Suppositories and/or enemas allow bowel regulation. It is important to avoid straining because the valsalva maneuver effects cardiac function, causing bradycardia and increasing orthostatic hypotension.

Alteration in sleep R/T obstructive sleep apnea

Patients with advancing MSA manifest respiratory stridor, inspiratory gasping, and dysrhythmic breathing and have periods of sleep apnea. Sleep studies are used to confirm the diagnosis of sleep behavior disorder (RBD) which is seen as increased electromyocgraphic (EMG) activity during REM sleep and active, sometimes combative movements that are associated with disturbing, unpleasant dreams. Upsetting dreams are effectively treated with clonazepam.9

Obstructive sleep apnea (OSA) becomes more severe in the latter stages of MSA. Loss of brainstem ventilator drive centers is thought to cause OSA, which is further enhanced by laryngeal dystonia. Patients with MSA show minimal response to hypoxia, particularly when sleeping, which may contribute to sudden death. One study showed that one-third of patients with MSA died suddenly.7 The use of C-PAP is very beneficial in treating apnea, increasing oxygen levels and allowing patients to have a restful, healthy sleep. This decreases fatigue, allows greater socialization and participation in activities.

Alt in self-esteem R/T dysphasia and isolation

With MSA hypophonia (low volume), monotonous speech and dysartria (poor articulation) are common speech abnormalities due to poor neuro-muscular function. In one study 100% of the patients with MSA-C had ataxic speech, which is described as monopitch, with irregular articulatory breakdown and bursts of loudness.10 Voice may be hoarse, if vocal cords remain in open position. A speech therapist’s evaluation will suggest appropriate exercises and devices that facilitate communication. Some patients find speech exercises very tiring and frustrating and prefer an alternative method of communicating e.g. pictures, communication board and/or lap top.