Shy-Dragger Syndrome – An underdiagnosed sad reality?

Multiple System Atrophy (MSA) regards a group of neurodegenerative diseases sharing the same physiopathology. It is a rare group of diseases and often represents a diagnostic challenge for clinicians. Mild symptoms are present at the onset of the disease and are often neglected by patients. The case report describes a 62-year-old female with multiple episodes of syncope with 3 months evolutions. Anamnesis revealed sleep apnoea and urinary incontinence. In order to perform complementary exams, the patient was admitted to the medical ward. Autoimunnity results were negative discarding this etiology; 24-hour arterial pressure monitoring revealed a severe fluctuation of tensional values capable of explaining syncope. Other exams revealed no pathological alterations responsible for the patient complaints. Multiple System Atrophy diagnosis was made after exclusion of other possible aetiological causes for the patient’s symptoms. More prevalent diseases such as Parkinson’s Disease, atypical Parkinsonic syndromes, and pure autonomic failure, among others may replicate the same symptoms. Diagnosing the patient with Multiple System Atrophy represented a challenge because of its rarity and clinical complexity. Being a disease with poor outcomes and representing necessary lifestyle changes to the patients and family life, an early and exact diagnosis may provide time and more life quality, within the disease limitations.

Internists are often presented with complex patients being obligated to gather all pieces, and put them together, so that de puzzle may be deciphered.

Learning points

- Multiple systems atrophy is a rare incapacitating disease and it is believed to be underdiagnosed;

- Complex diseases often present mild nonlimiting symptoms that patients might tend to neglect.

Case description

Introduction

Multiple System Atrophy (MSA) regards a group of neurodegenerative diseases sharing the same physiopathology. They are characterized by variable degrees of dysautonomia, cerebellar dysfunction, Parkinsonism, and cortico-spinal dysfunction [1,2]. Mental status is often preserved [3]. It is a rare condition, with the onset of symptoms typically between 50 and 55 years [4].

The cause of MSA is unknown [5]. Multiple mechanisms have been postulated even though it remains under investigation.

The diagnosis of MSA is based on clinical features. No laboratory or imaging studies are diagnostic.

Case report

The 62-year-old Caucasian female was referred to Internal Medicine consultation for multiple episodes of syncope. Relevant medical history included sleep apnoea, vertigo, depression, and urinary incontinence. Chronically medicated with fluoxetine 20mg twice daily, trimetazidine 35mg daily, and nocturnal CPAP. Upon asking the patient mentioned no relevant familiar medical history.

In the first consultation patient presented with complaints of paroxysmic episodes of generalized weakness associated with dizziness and blurred vision, sometimes ending with fainting. The patient reported a crisis with 3 months evolution. Clinical examination revealed obesity (Body Mass Index of 31%), slurred voice with a minor degree of dysarthria, intention tremor with severe dysgraphia, positive Romberg signal, normal arterial pressure in decubitus associated with orthostatic hypotension (Mean arterial pressure lower than 50 mmHg) with severe dizziness associated with postural changes.

The medical team decided to admit the patient to the medical ward for further exams, which included the results summarized in the following (Tables 1-3).

Before the results of complementary diagnostic exams and clinical manifestations with clear signs of Parkinsonism, cerebellar dysfunction, and dysautonomia, the medical team responsible for the patient made the diagnosis of Multiple System Atrophy, namely Shy Dragger Syndrome Subtype due to the predominance of dysautonomia. The patient was medicated with an Alfa-adrenergic agonist and Beta-Blockers for orthostatic hypotension, with only partial clinical response. Later, the patient was referred for medical consultation with a neurologist and a physiatrist.

Discussion

Multiple System Atrophy diagnosis is made after exclusion of other possible aetiological causes for the patient’s symptoms. More prevalent diseases such as Parkinson’s Disease, atypical Parkinsonic syndromes, and pure autonomic failure, among others may replicate the same symptoms. Differentiation between the different pathologies is a medical challenge, and the definitive diagnosis may be available only after post-mortem biopsies. Diagnosing the patient with Multiple System Atrophy represented a challenge because of its rarity and clinical complexity. Internists are often presented with complex patients being obligated to gather all pieces, and put them together, so that de puzzle may be deciphered. Literature regarding the disease often describes much earlier signs of the developing disease; in this case report, sleep apnoea and urinary incontinence were signs of such.

Treatment options are limited and directed only towards symptoms. Regarding treatments that alter the course of the illness, no medications are available. The patient developed severe symptoms of dysautonomia and died within two years. No autopsy was performed and therefore there is no information regarding brain biopsy.

We would like to thank Dr. Liliana Pinto for her contribution to proofreading the article.

1. Consensus statement on the definition of orthostatic hypotension, pure autonomic failure, and multiple system atrophy. The Consensus Committee of the American Autonomic Society and the American Academy of Neurology. Neurology. 1996 May;46(5):1470. doi: 10.1212/wnl.46.5.1470. PMID: 8628505.
2. Stefanova N, Bücke P, Duerr S, Wenning GK. Multiple system atrophy: an update. Lancet Neurol. 2009 Dec;8(12):1172-8. doi: 10.1016/S1474-4422(09)70288-1. PMID: 19909915.
3. Schatz IJ. Shy-Drager syndrome. N Engl J Med. 1985 Feb 7;312(6):378-9. doi: 10.1056/NEJM198502073120617. PMID: 3969092.
4. Tison F, Yekhlef F, Chrysostome V, Sourgen C. Prevalence of multiple system atrophy. Lancet. 2000 Feb 5;355(9202):495-6. doi: 10.1016/S0140-6736(00)82050-4. PMID: 10841152.
5. Wenning GK, Stefanova N, Jellinger KA, Poewe W, Schlossmacher MG. Multiple system atrophy: a primary oligodendrogliopathy. Ann Neurol. 2008 Sep;64(3):239-46. doi: 10.1002/ana.21465. PMID: 18825660.