Andrew J. Solomon

“Undiagnosing” multiple sclerosis: The challenge of misdiagnosis in MS

Objective: To describe the clinical characteristics of encounters with patients misdiagnosed with multiple sclerosis (MS). Methods: A cross-sectional Internet-based physician survey of MS specialists was performed. Results: The response rate for the survey was 50.4%. Of those who responded, the majority (95%) reported having evaluated 1 or more patients who had been diagnosed with MS, but who they strongly felt did not have MS, within the last year. The majority of respondents (>90%) also reported the use of disease-modifying therapy in a proportion of these patients. Most respondents (94%) found clinical encounters with these patients equally or more challenging than giving a new diagnosis of MS. Fourteen percent of respondents reported that they did not always inform such patients of their opinion that they did not have MS. Conclusions: The misdiagnosis of MS is common and has significant consequences for patient care and health care system costs. Caring for a patient with a misdiagnosis of MS is challenging, and at times honest disclosure of a misdiagnosis represents an important ethical concern for neurologists. More data are needed on this patient population to improve diagnostic acumen and the care of these patients.

Inflammatory neurological disease in patients treated with tumor necrosis factor alpha inhibitors

Background: TNF alpha inhibitor (TNFAI) therapy has been associated with inflammatory neurological syndromes. Objectives: To present 10 new cases of TNFAI associated neurological disease and a review of the literature. Methods: The design and methods were based on case series collected from Oregon Health & Sciences University and the Department of Veterans Affairs Hospital in Portland, Oregon and PubMed review. Results: We describe eight demyelinating central nervous system syndromes and two peripheral nervous system syndromes associated with TNFAI therapy. Characteristics from these cases are analyzed with data from 141 additional cases from the literature. Onset was between the ages of 36 and 65 years in 84% of CNS cases, distinguishing TNFAI-associated disease from sporadic multiple sclerosis. Symptoms occurred within one year of TNFAI therapy in 71%. Etanercept therapy was reported in the majority of cases of CNS syndromes and infliximab therapy in the majority of neuromuscular syndromes. Significant disability remained in 67% of cases although 82% had been followed for less than one year. Conclusions: Our case series and literature review demonstrates an association between TNFAI therapy and inflammatory neurological disease. While a causal relationship is suggested, this remains uncertain. TNFAI-associated neurological syndromes are associated with significant disability and longer follow-up is needed to better determine natural history and evaluate appropriate treatment interventions.

The central vein sign and its clinical evaluation for the diagnosis of multiple sclerosis: a consensus statement from the North American Imaging in Multiple Sclerosis Cooperative

Over the past few years, MRI has become an indispensable tool for diagnosing multiple sclerosis (MS). However, the current MRI criteria for MS diagnosis have imperfect sensitivity and specificity. The central vein sign (CVS) has recently been proposed as a novel MRI biomarker to improve the accuracy and speed of MS diagnosis. Evidence indicates that the presence of the CVS in individual lesions can accurately differentiate MS from other diseases that mimic this condition. However, the predictive value of the CVS for the development of clinical MS in patients with suspected demyelinating disease is still unknown. Moreover, the lack of standardization for the definition and imaging of the CVS currently limits its clinical implementation and validation. On the basis of a thorough review of the existing literature on the CVS and the consensus opinion of the members of the North American Imaging in Multiple Sclerosis (NAIMS) Cooperative, this article provides statements and recommendations aimed at helping radiologists and neurologists to better understand, refine, standardize and evaluate the CVS in the diagnosis of MS.

The contemporary spectrum of multiple sclerosis misdiagnosis: A multicenter study

Objective: To characterize patients misdiagnosed with multiple sclerosis (MS). Methods: Neurologists at 4 academic MS centers submitted data on patients determined to have been misdiagnosed with MS. Results: Of 110 misdiagnosed patients, 51 (46%) were classified as “definite” and 59 (54%) “probable” misdiagnoses according to study definitions. Alternate diagnoses included migraine alone or in combination with other diagnoses 24 (22%), fibromyalgia 16 (15%), nonspecific or nonlocalizing neurologic symptoms with abnormal MRI 13 (12%), conversion or psychogenic disorders 12 (11%), and neuromyelitis optica spectrum disorder 7 (6%). Duration of misdiagnosis was 10 years or longer in 36 (33%) and an earlier opportunity to make a correct diagnosis was identified for 79 patients (72%). Seventy-seven (70%) received disease-modifying therapy and 34 (31%) experienced unnecessary morbidity because of misdiagnosis. Four (4%) participated in a research study of an MS therapy. Leading factors contributing to misdiagnosis were consideration of symptoms atypical for demyelinating disease, lack of corroborative objective evidence of a CNS lesion as satisfying criteria for MS attacks, and overreliance on MRI abnormalities in patients with nonspecific neurologic symptoms. Conclusions: Misdiagnosis of MS leads to unnecessary and potentially harmful risks to patients. Misinterpretation and misapplication of MS clinical and radiographic diagnostic criteria are important contemporary contributors to misdiagnosis.

Misdiagnosis of Multiple Sclerosis: Frequency, Causes, Effects, and Prevention

A diagnosis of multiple sclerosis is heavily influenced by clinical judgment. Misdiagnosis of multiple sclerosis is common and has important consequences for patients and the cost of healthcare. Although rigorous data about the frequency and causes of misdiagnosis are lacking, misinterpretation and misapplication of clinical and radiographic diagnostic criteria and terminology are likely important factors. Appropriate and stringent application of diagnostic criteria and continued vigilance for “red flags” suggesting alternative diagnoses are strategies critical for prevention of misdiagnosis.

“Central vessel sign” on 3T FLAIR* MRI for the differentiation of multiple sclerosis from migraine

The diagnosis of multiple sclerosis (MS) presently relies on radiographic assessments of imperfect specificity. Recent data using T2* methodology for the detection of the “central vessel sign” (CVS) in MS lesions suggests this novel MRI technique may distinguish MS from other disorders. Our aim was to determine if evaluation for CVS on 3T FLAIR* MRI differentiates MS from migraine.

Autoantibodies and Sjogren’s Syndrome in Multiple Sclerosis, a Reappraisal

Background Rheumatologic diseases may cause neurologic disorders that mimic multiple sclerosis (MS). A panel of serum autoantibodies is often obtained as part of the evaluation of patients suspected of having MS. Objectives To determine, in light of recently revised diagnostic criteria for MS, neuromyelitis optica, and Sjogren’s Syndrome, if testing for autoantibodies in patients with a confirmed diagnosis of MS would reveal a frequency or demonstrate a clinical utility divergent from previous reports or lead to identification of undiagnosed cases of Sjogren’s Syndrome. Methods Convenience sample cross-sectional study of MS patients recruited from the OHSU Multiple Sclerosis Center. Results Autoantibodies were detected in 38% (35/91) of patients with MS and were not significantly associated with disease characteristics or severity. While four patients had SSA antibodies, none met diagnostic criteria for Sjogren’s Syndrome. Conclusions Rheumatologic autoantibodies are frequently found in MS patients and are not associated with disease severity or systemic rheumatologic disease. Our demonstration of the low specificity of these autoantibodies suggests that the diagnostic utility and cost-effectiveness of testing is not supported when there is strong clinical suspicion of MS and low clinical suspicion of rheumatologic disease.

A Clinical Approach to the Differential Diagnosis of Multiple Sclerosis

The diagnostic criteria for multiple sclerosis (MS) rely on clinical, paraclinical, and radiographic findings of limited specificity. Many disorders mimic MS, and the decision of when to investigate an alternative diagnosis can be challenging. Reliance on extensive ancillary testing to exclude potential mimics, however, is unnecessary in most cases. Rather, recognition and rigorous interpretation of “classic” clinical and radiographic features of MS are often sufficient to establish the diagnosis. Misinterpretation of the clinical and radiographic diagnostic criteria for MS in the setting of more common diseases and syndromes and a lack of vigilance for “red flags” are important contributors to misdiagnosis. A clinical framework for the differential diagnosis of MS that emphasizes phenotypes atypical for MS and suggests diseases or syndromes in which they more commonly occur may be an important diagnostic guide for clinicians in contemporary practice.

Multiple sclerosis and vitamin D

Vitamin D is a vitamin that acts like a hormone in the human body. We get vitamin D from sunlight, food, or dietary supplements. The study by Stein et al.1 examines the relationship of vitamin D and MS. In addition, a recent Patient Page in Neurology ® focused on the actions of vitamin D and vitamin D deficiency.2 The best level of vitamin D for health is uncertain and may vary depending on the part of the body vitamin D acts on. Many experts believe that blood levels of vitamin D above 30 ng/mL are adequate. (Some studies, such as the present study, use different units of measurement [nmol/L] than are common in the United States. A conversion factor of 2.496 is necessary to switch between these unit systems, and a vitamin D level of 30 ng/mL would be approximately 75 nmol/L in the present study.1) Vitamin D appears to act on a number of different systems in the human body. In particular, vitamin D seems to be important for function of the immune system. Therefore, deficiency of vitamin D may play a role in diseases thought to be caused by improper immune responses (autoimmune diseases), including multiple sclerosis (MS). A recent Patient Page in Neurology provided a thoughtful summary of what is known about MS.3 Previous studies have found that low vitamin D levels may increase the risk of developing MS.4,–,8 A number of studies have also suggested that patients with MS with low levels of vitamin D …

The tension between early diagnosis and misdiagnosis of multiple sclerosis

Abstract | Diagnosis of multiple sclerosis (MS) can be challenging, and misdiagnosis remains a persistent problem with considerable consequences for patients and health‐care systems. Common syndromes are frequently mistaken for MS. Misapplication of MS diagnostic criteria in patients with abnormal radiographic findings and clinical presentations that are atypical for MS is a frequent cause of misdiagnosis. Delays in diagnosis of MS and initiation of disease‐modifying therapy (DMT) are associated with an increased risk of disability, putting pressure on physicians to make therapeutic decisions for patients whose diagnosis remains uncertain. DMT is associated with unnecessary risks and morbidity in misdiagnosed patients. This tension between the benefits of an early diagnosis and the risk of misdiagnosis is a pressing problem. For patients who present with brain MRI abnormalities and clinical syndromes that are atypical for MS, strict adherence to MS diagnostic criteria and further clinical, laboratory and radiographic evaluation is prudent and likely to clarify a diagnosis.