64 YO male with an episode of syncope. He has 3 episodes this year. He has had problems at work where coworkers believed that he may have been drunk. He said he was slurring his speech and having an abnormal gait. He describes difficulty swallowing. He says it seems as if he cannot coordinate the muscles to make the swallowing happened. This is also intermittent but getting worse. Over the last few weeks he’s also had problems with urinary retention. He has had episodes of confusion whereby he had forgotten the names of people he was working with and got lost on the way home. He says the cognitive symptoms wax and wane. He is currently not having cognitive problems.
HR 105, otherwise normal
General: comfortable, slightly diaphoretic
Cardiac: RRR n/S1S2 no m/r/g
Mild dysarthria, and ataxic gait, difficulty with tremor when he attempts to do finger to nose. He has significant problems finding his nose when he tries to do finger to nose with his eyes closed. When his eyes are closed his balance is substantially worse and he has a tendency to fall (Positive Romberg test) . This corrects to some degree when he has his eyes open. He does not appear to be confused at this time.
He has had an MRI of the brain and an MR angiogram of his neck and head and there were no abnormal findings. He has seen neurology in the past and they have been uncertain as to the cause of his problems. The symptoms have been going on for 2 weeks but getting worse.He had these symptoms transiently in the past a few years ago but they resolved.
Neurology was consulted by us.
Neurology’s preliminary diagnosis is Shy-Drager syndrome.
– Do a neurologic exam that involves the patient walking. Do not assess the patient’s strength only while the patient is lying in bed. It is possible to miss cerebellar signs and gait ataxia when the patient is lying down. Use caution not to drop the patient or lip and fall when they’re standing. If you suspect a problem, get someone to help you do the exam.
– When you suspect a cerebellar problem, have the patient do the exam first with the eyes open then have the patient perform the exam with the eyes closed so the visual cues do not correct any of the exam findings.
– Take a very detailed history in patient’s who have vague or conflicting findings.
– Recognize that cerebellar signs and symptoms are not normally associated with cognitive problems. The fact that he has some thinking problems and confusion implies that there is more going on than a simple cerebellar problem.
-Both his urinary retention and his postural syncope can be explained by the autonomic abnormalities that are associated with Shy-Drager syndrome.
Multiple System Atrophy/Shy-Drager Syndrome
Multiple system atrophy (MSA) is a rare neurodegenerative disease marked by a combination of symptoms affecting movement, blood pressure, and other body functions; hence the label “multiple system” atrophy. According to the American Autonomic Society, Multiple System Atrophy (MSA) is a sporadic, progressive, adult-onset disorder characterized by autonomic dysfunction, parkinsonism and ataxia (a failure of muscular coordination) in any combination
The average age of onset is in the sixth decade of life. Men are affected twice as frequently as women are. In some patients, chronic orthostatic hypotension may be a presenting symptom, but in other cases, extrapyramidal symptoms or cerebellar symptoms may predominate in the early stages. When the chronic orthostatic hypotension antedates other neurological involvement, it may be very difficult to differentiate MSA from the more benign pure autonomic failure (PAF). Patients complain of impotence, change in writing style, slurred speech, sleep apnea, difficulty with urination, frequent urinary tract infections, a hoarse voice, passing out, headache, neck pain, dimming of vision and yawning. Syncope, or passing out, is most frequently associated with orthostatic hypotension, or a low blood pressure with standing, even though blood pressure while lying down may be very high. There are several unusual features of multiple system atrophy that are often missed, but may be important in making this diagnosis. Patients frequently note emotional lability, with short (sometimes only one or two minutes) episodes of crying due to happiness or sadness in response to relatively minor environmental stimulus, such as a song, a television program, or a movie. This is usually self-limited, but may be a harbinger of depression. Patients sometimes have periodic gasping respirations punctuating the medical interview. They only last a few seconds, are not generally deep, but seem labored. Finally, many patients will discontinue the use of nicotine-containing products at the onset of their disease. It sometimes appears that they no longer enjoy the nicotine. Ultimately, nicotine may provoke worsened tremor in some of these patients. A final symptom which occurs in occasional patients with multiple system atrophy is diplopia, not unlike that seen in multiple sclerosis. Pathologically, there is involvement of multiple sites within the brain and spinal cord. A glial cytoplasmic inclusion has been found to occur intracellularly in both glial cells and neurons of involved portions of the brain. This has been seen in patients carrying the clinical diagnosis of Shy-Drager syndrome, sporadic oligopontocerebellar atrophy, striatonigral degeneration, and corticobasal degeneration. These inclusions contain ubiquitin, but are quite distinct from Lewy bodies, which also contain ubiquitin. The glial cytoplasmic inclusions tend to be irregular in outline in contrast to the target-shaped concentric circular Lewy bodies. Some investigators have suggested a relationship between the Shy-Drager syndrome and Parkinson’s disease, although this is not supported by the pathologic data accumulated to date. Lewy bodies have been absent in several careful autopsies of Shy-Drager patients (Heieren, 1972). At least one family has been reported in whom four members had a Shy-Drager-like syndrome (Lewis, 1964), but there is no other suggestion of a strong genetic component in the disease, and the actual diagnosis in this reported family may not have been MSA.
Blood and urinary levels of norepinephrine are often near normal in the unstimulated state in patients with MSA, but they do not rise appropriately on assumption of the upright posture (Ziegler et al., 1977). Peripheral norepinephrine levels tend to be higher in MSA than in PAF. Catecholamine metabolites reflect the central nature of the neurological defect (Polinsky et al., 1981; Kopin et al., 1983; Polinsky et al., 1984; Polinsky et al., 1987). It is noteworthy that there is also biochemical evidence of central abnormalities in the dopamine, acetylcholine and serotonin systems (Polinsky et al., 1988; Polinsky et al., 1989).
Diagnosis of MSA can be challenging because there is no test that can make or confirm the diagnosis in a living patient. Certain signs and symptoms of MSA also occur with other disorders, such as Parkinson’s disease, making the diagnosis more difficult.
If your doctor suspects multiple system atrophy, he or she will obtain a medical history and perform a physical examination. You may receive a referral to a neurologist or other specialist for specific evaluations that can help in making the diagnosis.
Tests that may be helpful in making a diagnosis include:
Tilt table test – In this procedure, your blood pressure is monitored while you are on a special table that will tilt you to an almost upright position. This allows the physician to record blood pressure irregularities, and information about whether they occur with a change in physical position.
A sweat test to evaluate perspiration
Tests to assess your bladder and bowel function
Electrocardiogram to track the electrical signals of your heart
Brain-imaging tests, particularly a magnetic resonance imaging (MRI) scan, to determine if another condition might be triggering symptoms
Pharmacological challenge tests (administering certain medications and observing the patient’s body’s reaction to them, in controlled clinical settings)
True diagnosis can only be accomplished by examination of the brain post-mortem.
For patients with sleep irregularities, particularly if they involve interrupted breathing or snoring, physicians may recommend an evaluation in a sleep laboratory to determine if there is an underlying and treatable sleep disorder, such as sleep apnea.
The prognosis is more guarded in the multiple system atrophy patient than in pure autonomic failure. It is rare for a patient to survive 10 years. The autonomic abnormalities are seldom the direct cause of death A significant number of patients develop laryngeal stridor and difficulty swallowing, which can lead to pneumonia. In addition, many patients with MSA experience Cheyne-Stokes or periodic respiration and in some cases this may lead to a critical loss of respiratory drive, so called Ondine’s curse (Craddock et al., 1987). Pulmonary hypertension may occur during apnea (Guilleminault et al., 1977). The most common causes of death in patients with MSA are pulmonary embolus, apnea, and intercurrent infection.
There is no known cure for multiple system atrophy, so management involves treating specific problems in this patient population. This includes treatment of the depression, tremor and gait disturbances, supine hypertension, orthostatic hypotension, and possible self-catheterization.