Hindsight Is 20/20

Multiple sclerosis is a chronic demyelinating disease of the CNS.¹ The diagnosis of MS has classically been based upon compatible clinical and radiographic evidence of pathology that is disseminated in space and time. Patients typically present with an initial clinically isolated syndrome—involving changes in vision, sensation, strength, mobility, or cognition—for which there is radiographic evidence of demyelination.² A diagnosis of clinically definite MS is then often made based on a subsequent relapse of symptoms.³

An interval from initial symptoms has been central to the diagnosis of MS (“lesions disseminated in time”). However, recent evidence questions this diagnostic paradigm, and a more rapid diagnosis of MS has been recommended. This recommendation is reflected in the updated McDonald criteria, according to which, if a clinical presentation is supported by the presence of oligoclonal bands in the cerebrospinal fluid, a diagnosis can be made on the basis of radiographic evidence of dissemination of disease in space, without evidence of dissemination in time.⁴ The importance of such early diagnosis has been supported by numerous studies that have demonstrated improved clinical outcomes with early therapy.^5-7

Despite the McDonald criteria, delays in definitive diagnosis are common in MS. Patients with MS in Spain were found to experience a 2-year delay from the first onset of symptoms to diagnosis.⁸ In this cohort, patients exhibited delays in presenting to a healthcare provider, as well as delays in diagnosis with an average time from seeing an initial provider to diagnosis of 6 months. When patients who were referred for a demyelinating episode were surveyed, over a third reported a prior suggestive event.⁹ The time from the first suggestive episode to referral to a neurologist for a recognized demyelinating event was 46 months. Other studies have shown that delays in diagnosis are especially common in younger patients, those with primary progressive MS, and those with comorbid disease.^10,11

Misapplication of an MS diagnosis also occurs frequently. In one case series, such misapplication was found most often in cases involving migraine, fibromyalgia, psychogenic disorders, and NMOSD.¹² NMOSD is distinguished from MS by the presence of typical brain and spine findings on MRI.¹³ Antibodies to aquaporin-4 are highly specific and moderately sensitive for the disease.¹⁴ It is important to distinguish NMOSD from MS as certain disease-modifying drugs used for MS might actually exacerbate NMOSD.¹⁵ A lesion that traverses over three or more contiguous vertebral segments with predominant involvement of central gray matter (ie, longitudinally extensive transverse myelitis) on MRI is the most distinct finding of NMOSD. In contrast, similar to our patient, short and often multiple lesions are demonstrated on spinal cord MRI in patients with MS. Sensitive and specific findings of brain MRI in patients with MS include the presence of lateral ventricle and inferior temporal lobe lesion, Dawson’s fingers, central vein sign, or an S-shaped U-fiber lesion. In NMOSD, brain MRI might reveal periependymal lesions surrounding the ventricular system.

This case highlights the diagnostic challenges related to presentations of a waxing and waning neurological process. At the time of the second evaluation, the presentation was interpreted as a length-dependent polyneuropathy due to glucose intolerance. Our patient’s relatively normal HbA1c, subacute onset of neuropathic symptoms (ie, <4 weeks), sensory and motor complaints, and onset in the upper extremities suggested an alternative diagnosis to prediabetes. Once the patient presented with optic neuritis, the cause of the initial symptoms was obvious, but then, hindsight is 20/20.