Study Highlights Significant Challenges in Early Diagnosis of MS

Confident female doctor reviews a patient’s medical information. The doctor is pointing to something on the patient’s medical forms. The doctor is wearing a stethoscope.
In this editorial, study researchers discussed the possible prodromal phase of multiple sclerosis and its role in the early diagnosis of the disease.

Early diagnosis of multiple sclerosis (MS) remains a significant challenge. Findings from a recent study, published in Neurology, suggested that missed demyelinating events that occur years prior to diagnosis may better identify the disease earlier in its course, while early symptoms seemingly related to MS may actually be ongoing disease vs a prodrome.

“Prodrome” has come to refer to a set of symptoms suggestive of disease prior to the emergence of diagnostically specific signs and symptoms. Recent studies suggest there may be a prodromal phase of MS, pointing in particular to the increased prevalence of symptoms, diagnoses, and healthcare utilization in patients several years prior to MS diagnosis. Symptoms that often appear prior to MS diagnosis include fatigue, depression and/or anxiety, headache, pain, sleep disturbances, and gastrointestinal disorders.

In the recent study, researchers examined the early prevalence of these conditions and symptoms up to 5 years prior to MS diagnosis in patients included in a German administrative database. The study included incident MS cases from 2010 to 2017.

The study investigators identified 10,262 patients with MS and compared these cases with 113,984 patients with autoimmune disease and 73,430 patients without autoimmune disease. They identified 43 ICD-10 codes more frequently reported in patients with MS prior to diagnosis, with most of these codes suggestive or indicative of neurologic disorders or symptoms.

In a repeated analysis that excluded patients with ICD-10 codes associated symptoms indicative of MS relapse 5 years prior to diagnosis, not 1 of the remaining ICD-10 codes were found to be significantly associated with MS. There was an inverse association between MS and codes for upper respiratory infections.

Given this research relied on administrative health data, the study may be limited by its inability to determine whether the neurologic diagnoses and symptoms actually represented MS, demyelinating events, or other neurologic-related diagnoses.

The editorial authors suggested that “progress toward removing obstacles to early MS diagnosis will require health care system and provider-level quality improvement efforts in neurology and in collaboration with our [non-neurologist] colleagues.”

Disclosure: Multiple authors declared affiliations with the pharmaceutical industry. Please refer to the original article for a full list of disclosures.


Solomon AJ, Ascherio A. Early diagnosis of multiple sclerosis: Further evidence for missed opportunity. Neurology. Published online June 15, 2021. doi:10.1212/WNL.0000000000012087