Wednesday, 1 August 2018

Guest post - Reducing MS misdiagnosis: The MS Lesion Checklist

It is estimated that 5-13% of patients diagnosed with MS do not have MS (Solomon et al, Curr Neurol Neurosci Rep, 2013). As MS prevalence in the US may be as high as 208/100,000 persons (Wallin et al, 2017), this would translate into almost 700,000 cases of MS, of whom as many as 70,000 could be misdiagnosed. 

To put this in perspective: the number of persons who carry the diagnosis of MS without having MS is several-fold higher than then the number of patients with ALS (motor neurone disease) (~13,000 cases in the US) and NMO (Devic's disease) (~17,000 cases in the US (Flanagan et al., 2016)).  The magnitude of the problem is highlighted by a survey of 112 MS specialists across the US, who reported seeing, on average, 5-6 patients a year with ‘near-certain MS misdiagnosis’, half of whom were receiving disease-modifying therapy (DMT) for MS [Solomon et al, Neurology, 2015].

Paradoxically, the most useful tool for confirming MS diagnosis – MRI – has become the most common contemporary cause of MS misdiagnosis (Solomon and Weinshenker, 2013). In large part, this may be due to the fact that white matter lesions are not infrequent in the general population, even among younger people and radiology reports often make mention of ‘demyelination’ as a possible cause, even when MRI evidences no features specific for demyelination. Combination of non-specific neurologic symptoms and “demyelinating” brain lesions can (mis)lead the clinician along the path of MS misdiagnosis.

To remedy the situation, I propose the MS Lesion Checklist as a screening tool to ‘rule out’ demyelinating disease in a low-probability patient (no history of MS-like relapses and normal neurological examination). The main argument – which will require validation in future studies – is that absence of lesions typical for demyelination makes the diagnosis of MS untenable. The key question is whether the given patient’s MRI shows any lesions typical of demyelination or not. 

The proposed ‘MS Lesion Checklist’ contains 10 types of lesions that are not only common in MS, but also help to differentiate it from other etiologies, most importantly vascular disease and normal ageing. Even a patient with numerous white matter lesions should not be diagnosed with MS if none (or very few) of their lesions are of the kind seen in MS (some caveats apply, as discussed in the body of the article).

It is the author’s hope that use of this simple tool will help cut down on rates of MRI-supported MS misdiagnosis and improve to improve MRI reporting in suspected MS.

Flanagan, E. P. et al. (2016). Epidemiology of aquaporin-4 autoimmunity and neuromyelitis optica spectrum. Annals of Neurology.
Solomon, A. J., & Weinshenker, B. G. (2013). Misdiagnosis of multiple sclerosis: frequency, causes, effects, and prevention. Current Neurology and Neuroscience Reports, 13(12), 403.
Solomon et al. The contemporary spectrum of multiple sclerosis misdiagnosis. Neurology 2016;87:1393-1399
Wallin M. The Prevalence of Multiple Sclerosis in the United States: A Population-Based. Healthcare Database Approach. ECTRIMS Online Library Oct 26, 2017; 199999.

By Ilya Kister MD, FAAN 

Ilya is a graduate of Mount Sinai School Medicine in New York, Albert Einstein College of Medicine Neurology Residence Program in the Bronx and NYU MS Fellowship in New York. He is currently the director of NYU Neuromyelitis Optica Research and Development Program and NYU Multiple Sclerosis Fellowship. He is active in clinical research and has published over 60 peer-reviewed research papers and review articles.

The author has served on scientific advisory boards for Biogen Idec and Genentech and received research support from Guthy-Jackson Charitable Foundation, National Multiple Sclerosis Society, Biogen-Idec, Serono, Genzyme, Genentech, and Novartis.


  1. What about the generalization of Dawson's fingers, namely the central vein sign that is gaining momentum? It is not in the checklist, although there is a reference to a relevant study (13).

  2. Central vein sign is very helpful, but requires optimized T2* sequence, which is not available to most clinicians. The checklist only requires standard T2/FLAIR to make it more practical.
    Thanks for your comment.

    Ilya Kister


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