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Psychosomatics 46:73-76, February 2005
© 2005 The Academy of Psychosomatic Medicine

Case Report

Shy-Drager Syndrome: Multisystem Atrophy With Comorbid Depression

Jean Hemingway, M.D., Kathleen Franco, M.D., and Elizabeth Chmelik

Received May 27, 2004; accepted June 25, 2004. From the Department of Psychiatry and Psychology, Cleveland Clinic Foundation. Address reprint requests to Dr. Franco, Department of Psychiatry and Psychology, Cleveland Clinic Foundation, 9500 Euclid Ave., P57, Cleveland, OH 44195; francok{at}ccf.org (e-mail).

In 1960, Shy and Drager 1 described a progressive neurodegenerative disease of unknown etiology. Shy-Drager syndrome can involve the central autonomic, cerebellar, basal ganglia, pyramidal, and spinal motor neurons.2 Criteria for diagnosis include autonomic failure, cerebellar signs, pyramidal signs, and parkinsonian features.3 One-third of the patients with Shy-Drager syndrome also have respiratory stridor and stimulus-sensitive finger myoclonus and will not improve with levodopa trials.3 Severe autonomic insufficiency causes wide swings in blood pressure without altering pulse rate.2,4 Other symptoms include rigidity, masked facies, bradykinesia, urinary and rectal incontinence, impotence, hypohidrosis, intention tremor, dysarthria, ataxia, snoring, and apnea.2 Male patients outnumber female patients by a ratio of 2:1.5,6 The mean age at onset is 55, with a median survival of 7.5 years.5,6

Graham and Oppenheimer 7 introduced the term "multiple system atrophy" to include Shy-Drager syndrome, striatonigral degeneration, and olivopontocerebellar atrophy, with all including parkinsonism, cerebellar dysfunction, and autonomic dysfunction but varying in course.8 Early autoimmune symptoms can be misdiagnosed as pure autonomic failure, while extrapyramidal and cerebellar problems developing later resemble Parkinson’s disease.4,9 Misdiagnosis is particularly common with Parkinson’s disease if the integration of symptoms and rate of progression are not considered.10,11 Diverse risk factors for progression and survival also differentiate multiple system atrophy from Parkinson’s disease.9,11

We will present a case demonstrating how diverse symptoms can be mistaken for and treated as isolated disorders, prolonging the period before diagnosis and family education. This report also reviews treatment issues regarding severe comorbid depression.

Case Report

Mr. A, a 48-year-old white man with a 20-year history of Crohn’s disease, hypothyroidism, hypercholesteremia, and bipolar disorder went to a hospital with a 10-month history of weakness and episodic falls. After an extensive workup showed him to be normal, he was treated and transferred for a second opinion. His admission medications included 0.05 mg/day of levothyroxine, 0.1 mg b.i.d. of florinef, 10 oral mEq b.i.d. of potassium, 4 g b.i.d. of cholestyramine, two salt tablets t.i.d., 30 mg q.i.d. of phenelzine, 300 mg b.i.d. of lithium carbonate, 0.5 mg b.i.d. of lorazepam, 400 mg of magnesium oxide at bedtime, 30 oral mg/day of lansoprazole, 2.5 mg t.i.d. of bromocriptine, and 20 mg t.i.d. of methylphenidate.

Upon questioning, Mr. A acknowledged having incontinence and impotence for over 5 years. His examination was significant for masked facies, increased rigidity of all extremities, mild cogwheeling, hyperreflexia, a wide-based stance, bradykinesia, a shuffling gait, and slurred speech. His blood pressure at admission was 102/60 mm Hg when he was lying down, 99/70 sitting, and 94/61 standing. He tolerated the tilt table at 30° for only 2 minutes before terminating the test. His blood pressure declined rapidly and was 54/30 mm Hg at maximum tilt. Near the end of his 14-day hospital stay, he could stand or sit for no longer than 60 seconds.

On the Mini-Mental Status Examination, he received a score of 16 of 30, losing points in recall, calculation, and orientation. His laboratory test results were normal for a complete metabolic panel, thyroid function tests, mitochondrial antibody tests, blood cultures, an HIV test, fungal cultures, CSF cultures, and an acid-fast bacilli culture. After the internal medicine department ruled out adrenal insufficiency, the psychiatry team suggested Shy-Drager syndrome.

Although phenelzine would contribute to hypotension, this was the only medication that had successfully treated Mr. A’s severe depression. Over many years, he had tried every new antidepressant. Even ECT had failed to show lasting benefits. Mr. A had been hospitalized three times for severe depression and serious suicide attempts. The risks and benefits of the drug were discussed with Mr. A and his wife and because of persistent suicidal thoughts, both preferred that he continue taking phenelzine.

At one point during his 2-week hospital stay, Mr. A developed paranoid delusions, which quickly resolved with risperidone. He was discharged to a skilled nursing facility with his admission medications and the addition of 0.5 mg/day of risperidone, as needed. We sadly note that Mr. A died 2 weeks later.

Discussion

Shy-Drager syndrome is a progressive, nonfamilial, sporadic disorder of unknown incidence. A dysfunctional autonomic nervous system causes many presenting features and tempts specialists to identify and treat each symptom as if it were a separate disorder. Orthostatic hypotension alone was insufficient to diagnose the patient with Shy-Drager syndrome because only 11% of the patients with orthostatic hypotension have Shy-Drager syndrome.12 Orthostatic hypotension has multiple causes, including baroreflex failure, vascular insufficiency, and other miscellaneous causes, such as drugs.13 It was essential for orthostatic hypotension to be viewed in concert with the patient’s other symptoms in order to make the correct diagnosis, but it was easy to be led astray if one studied each manifestation in isolation without considering the whole picture. Table 1 outlines some characteristics of Parkinson’s disease, Shy-Drager syndrome, olivopontocerebellar atrophy, and progressive supranuclear palsy that can help differentiate these disorders.


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TABLE 1. Differential Symptoms/Findings of Parkinson-Like Disordersa



The symptoms of Shy-Drager syndrome overlap with other disorders, and not all patients experience all symptoms (see Table 1). If Shy-Drager syndrome is suspected, a magnetic resonance image may identify an abnormal signal from the putamen that is more evident as the disease progresses.11,14,15 Urodynamic tests and sphincter electromyograms, normal in Parkinson’s disease, are abnormal with any progressed multiple system atrophy, while hyperreflexia occurs early in multiple system atrophy and much later in Parkinson’s disease.16 Current research may determine if response to clonidine and growth hormone will differentiate these disorders, but the first step in diagnosis remains recognition of symptom clusters.17

We do not know the patient’s cause of death, but abnormal respiration and sudden death during sleep are not unusual.18 Although vocal cord paralysis was not noted by Shy and Drager, it appears to be common and is perhaps a "marker."18–21 Limitation of vocal fold abduction occurs only during sleep in most patients with multiple system atrophy, causing significant airway compromise.19,20,22,23 If identified, preventive treatments are recommended and may include nighttime monitoring, continuous positive airway pressure, and a tracheostomy.18,21,24,25

In one study of 15 patients with Shy-Drager syndrome, 28.6% had moderate to severe depression compared to 3%–4% of healthy individuals, suggesting an increased prevalence,26 although others refute this claim.27,28 Regardless of prevalence, depression does occur and requires careful determination of treatment to avoid additional orthostasis.27 Our patient chose to continue taking phenelzine because it was the only medication that had helped him, despite many other trials. Generally, this would not be the first choice, since it can contribute to hypotension.

An extremely important consideration is the emotional impact on the family. Physical disabilities develop early, but intellectual and emotional functions are generally preserved until quite late in the illness course.27 In our case, the patient was able to participate in decisions about his medication and was aware of his condition, despite problems with orientation and recall. Given that Shy-Drager syndrome is unique in its clinical presentation, caregivers are confronted with problems that are not typically seen in other diseases.29 There is an increased risk of depression, anxiety, anger, and physical illness in caregivers. Both family and patients desperately need support and extensive education.27 In our case, a therapeutic alliance with the patient’s wife supported her efforts during and after the difficult decision making for her husband’s care.

Conclusion

Shy-Drager syndrome is a devastating disease that may mimic other disorders at different points along its course. These can be mistaken for separate disease entities, confusing a patient’s care and his caretakers. Although this syndrome has traumatic effects and often causes early death, a multidisciplinary team’s effort to coordinate diagnosis, education, and emotional support for the patient and family is something we can and should offer.

REFERENCES

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* Other Neuropsychiatric Disorders
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