HILTON HEAD—Although multiple system atrophy (MSA) cannot be cured, neurologists can help patients manage its associated symptoms such as bladder and autonomic dysfunction. MSA may cause symptoms similar to those of Parkinson’s disease, and the ability to distinguish between the two disorders is essential for providing an accurate prognosis, according to a lecture given at Vanderbilt University’s 38th Annual Contemporary Clinical Neurology Symposium.
MSA, formerly known as Shy–Drager syndrome, is an alpha-synuclein-related pathology like Parkinson’s disease. Alpha-synuclein accumulates in the glia in MSA, while it accumulates in the neurons in Parkinson’s disease. Between four and five people per 100,000 have MSA, and incidence increases with age. Onset typically occurs during the sixth decade of life, and the disorder affects men and women at equal rates.
Clinical Presentation Is Crucial
MSA is characterized by progressive autonomic failure, parkinsonian features, and cerebellar signs, and some patients have pyramidal signs, said Peter Hedera, MD, PhD, Associate Professor of Neurology at Vanderbilt University School of Medicine in Nashville.
Peter Hedera, MD, PhD
As its name implies, MSA affects many bodily systems. Early in the disease, patients often have urologic problems such as urinary urgency, nocturia, urinary urge incontinence, and urinary retention. Erectile dysfunction is common among men at MSA onset, and women with the disorder often have genital hyposensitivity during intercourse.
Neurogenic orthostatic hypotension also arises early in MSA, but patients may have supine hypertension, too. The diagnosis of MSA requires a reduction in systolic blood pressure of at least 30 mmHg after three minutes of standing from a recumbent position. Patients may present with fainting, lightheadedness, or dizziness, but these symptoms are nonspecific. Obtaining standing blood pressure and asking patients to keep a blood pressure log can help establish neurogenic orthostatic hypotension, said Dr. Hedera.
More than 80% of people with MSA have REM sleep behavior disorder, which has emerged as a sensitive indicator of MSA. Patients with REM sleep behavior disorder typically act out their dreams or shout in their sleep. “It’s so sensitive to MSA that if I hear about it, and other features [are consistent with MSA], I’m quite satisfied with the diagnosis,” said Dr. Hedera.
MSA also is associated with stridor and head drop, and these symptoms should raise neurologists’ suspicion of MSA. Dementia and visual hallucinations, however, are rare in MSA and should prompt neurologists to consider diagnoses such as Lewy body dementia or Parkinson’s disease.
If a patient presents with parkinsonism on both sides of the body, it is unlikely that he or she has Parkinson’s disease, which typically has an asymmetric presentation, said Dr. Hedera. Similarly, if a patient has a history of falls early in the disease course, the diagnosis is more likely to be MSA or other types of parkinsonism than Parkinson’s disease. Although falls are associated with Parkinson’s disease, they tend to occur later in the disease course.
Imaging May Support the Diagnosis
Although clinical criteria are more important for establishing a diagnosis of MSA, imaging can be useful, said Dr. Hedera. Patients with MSA often have atrophy in the cerebellum or brainstem, but these signs are not specific to the disorder. Pontine pathology, especially the hot-cross-bun sign, is a helpful indicator of possible MSA.
A DAT scan indicates striatal dopamine binding. Although this technique can establish dopaminergic denervation, “it doesn’t differentiate between Parkinson’s disease and MSA,” said Dr. Hedera.
An MIBG scan allows neurologists to visualize neuroadrenary uptake and catecholaminergic innervation in vivo. It also enables neurologists to distinguish between central autonomic failure, which may indicate MSA, and peripheral autonomic failure, which may indicate Parkinson’s disease. Neurologists should consult with their nuclear medicine specialists to identify the cutoff between peripheral and central autonomic failure, said Dr. Hedera. MIBG scans should be conducted after a four-hour delay and after the ratio between heart and mediastinum uptake is determined.
Prognosis and Management of MSA
MSA is a more aggressive disorder than Parkinson’s disease, said Dr. Hedera. The mean survival from onset of MSA symptoms is between six and 10 years. Few patients survive for more than 15 years after symptom onset.
Some patients with MSA may respond to levodopa, but the response is poor and typically not sustained. Patients also may develop complications from levodopa therapy. A dose of at least 2 g will ensure that a levodopa trial is sufficient, said Dr. Hedera.
Neurologists may recommend compression stockings and increased salt and fluid intake to reduce neurogenic orthostatic hypotension. Increasing fluid intake may be problematic, however, for patients with urinary urgency or nocturia. Neurologists should recommend that patients lie at a 30° angle, perhaps by using several pillows, instead of lying flat while they sleep. “Always advise them not to lie down during the daytime,” said Dr. Hedera.