Neurodegenerative Disorders Often Misdiagnosed in the Context of Rheumatic Disease

Case studies published recently have shed light on the clinical challenges, diverse presentation, and potential mechanisms related to co-occurring rheumatic diseases and neurodegenerative disorders.

Rheumatic diseases can co-occur with movement and other neurodegenerative disorders that are associated with problems such as early mortality, psychosocial morbidities, osteoporotic fractures, and wheelchair dependence. The vast heterogeneity between these disorders, and their overlapping clinical features, can further cloud the diagnostic evaluation. 

Movement disorders and other neurodegenerative diseases may be underdiagnosed or misdiagnosed in patients with rheumatic disease. “It is often difficult for patients and physicians to know whether a problem with walking, for example, is due to involvement of the joints or a neurologic disorder that can also affect how well a person walks,” Eric Matteson, MD, professor of medicine and chair of the Department of Rheumatology at Mayo Clinic in Rochester, Minnesota, told Rheumatology Advisor.

With the aim of identifying distinct phenotypes and potential mechanisms, physicians at Johns Hopkins University School of Medicine conducted a systematic review of literature and integrated it with case presentations of 8 patients with comorbid rheumatic and neurodegenerative disorders. Their findings were published online in August 2015 in the journal Medicine. Because of the wide spectrum of clinical injury that can present with movement and other neurodegenerative disorders in rheumatic disease, a significant clinical challenge is having an adequate level of familiarity with these disorders that are sometimes misdiagnosed as Parkinson disease. 

Alternately, Parkinson disease may be overlooked and mistaken for another type of disorder:  “In my experience, the opposite tends to be true and several patients are misdiagnosed with a rheumatic or orthopedic condition before the proper diagnosis of Parkinson disease or Parkinsonian syndrome is properly formulated,” notes Michele Tagliati, MD, a professor and vice chair with the department of neurology, and director of the Movement Disorders Program, at Cedars-Sinai Medical Center in Los Angeles.

“This is particularly true with younger patients, because Parkinson disease is not expected and immediately considered in patients younger than 50,” he told Rheumatology Advisor, further underscoring the need for a thorough understanding of the disease and other neurodegenerative disorders.

A second challenge is determining whether these disorders are noninflammatory and unrelated to the rheumatic disease, or due to the rheumatic disease and driven by immune-mediated processes. “Some diseases like ALS or Parkinson can occur in a person with a rheumatic disorder, but not be at all related to the rheumatic disorder, instead occurring as they would in people without rheumatic diseases, while some rheumatic disorders–for example, Sjögren Syndrome, vasculitis, and systemic lupus erythematosus–actually cause movement disorders,” explains Dr Matteson. “It is important to recognize this, because successful treatment of the movement disorder is predicated on successful treatment of the rheumatic disease,” he says.

Of the patients described in the August paper, several had been misdiagnosed with Parkinson disease though none of them were ultimately determined to have it; 5 were diagnosed with Sjögren syndrome and 2 with undifferentiated connective tissue disease. Similarly, the authors’ review of the literature revealed that patients with concurrent rheumatic disease and movement disorders rarely presented with Parkinson disease.

Another important discovery in the case studies described in the current paper is that, in addition to the rheumatic disease, some of the individual patients had features of multiple movement and other neurodegenerative disorders that are each quite rare, with “collective probabilities of [approximately] 1 per billion if merely coincidental, unrelated, and not unified by immune-mediated mechanisms,” the authors wrote.

Though they considered the possibility that a diffuse vasculopathy might account for the widespread pattern of clinical injury observed in these patients, their MRI studies did not support this explanation. An alternate possibility is the presence of antineuronal antibodies, which may ubiquitously target shared autoantigens dispersed in different peripheral and central nervous system compartments.

“The widespread pattern of clinical injury, the propensity of our patients to present with co-occurring movement disorders, and the lack of MRI neuroimaging findings suggestive of a vasculopathy collectively suggest unique patterns of immune-mediated injury,” they concluded. 

In addition to patterns observed in the 7 patients mentioned above, the authors present the case of a patient with psoriatic arthritis who developed an amyotrophic lateral sclerosis (ALS)-plus syndrome following tumor necrosis factor (TNF)-inhibitor therapy. This patient was also found to have markers of inflammation and immune-mediated injury, including antineural antibodies, suggesting that the syndrome was likely iatrogenically induced.

Summary & Clinical Applicability

Overall, these findings shed light on the clinical challenges, diverse presentation, and potential mechanisms related to co-occurring rheumatic disease and neurodegenerative disorders and highlight the importance of a multidisciplinary approach.

“If there is a suspicion of movement disorder or other neurodegenerative conditions, including Alzheimer disease or ALS, a neurological consultation can readily help [confirm] the diagnostic suspicion and eventually define whether one of the less common diseases reported in the article may be in the differential,” advises Dr Tagliati.

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Menezes R, Pantelyat A, Izbudak I Birnbaum J. Movement and other neurodegenerative syndromes in patients with systemic rheumatic diseases. Medicine (Baltimore). 2015; 94(31): e0971.