Diagnostic Delays Drive Misdiagnoses in MS

Misdiagnoses in multiple sclerosis (MS) are often driving factors in patients experiencing diagnostic delays (DDs), according to a study published in Multiple Sclerosis Journal. Consequently, those affected by these delays often endure greater disease-related burdens.

One of the prominent problems in MS, for patients, researchers, and clinicians, is the possibility of DDs. Earlier treatment initiation has shown the potential to drastically improve disability, disease relapse, and brain atrophy, among other benefits. Current guidelines advocate for diagnosis within 12 weeks of symptom onset to begin disease-modifying treatment (DMT).

Misdiagnosis Text, Stethoscope, Syringe, Medication | image credit: Fauzi - stock.adobe.com

“The prevalence of DD remains high but has improved. Predisposing factors include health care system barriers, comorbidities, primary progressive MS, and lower education, but the exact determinants in individual patients are often unclear. Furthermore, the relationship between diagnostic and DMT delays, and disease activity is not well described. Understanding the specific determinants of DDs would help accelerate the diagnostic process,” lead author Tomas Uher, MD, of Charles University in Prague and colleagues wrote.

To expand this knowledge, their team conducted a large single-center study to shed light on the consequences, prevalence, and determinants of DD in patients with relapsing/remitting MS (RRMS).

Between November 2016 and February 2021, 146 patients with RRMS were observed at the referral MS Centre of the General University Hospital in Prague. Each patient underwent a cerebrospinal fluid (CSF) examination to confirm their diagnosis, and this group included individuals who received their diagnosis in the Czech Republic to avoid potential language or health care system barriers in their analysis. Researchers evaluated Expanded Disability Status Scale (EDSS) scores and CSF and serum samples, measured neurofilament light chain (NfL) levels, and conducted MRI exams. Furthermore, neurological medical histories were reviewed to determine if any previous symptoms fulfilled MS-relapse criteria—thus indicating prior demyelination, MS onset, and the possibility of DDs (defined as more than 3 months occurring between symptom onset and diagnosis of MS).

In total, researchers observed DD in 77 patients (52.7%), with 63 patients (43.2%) experiencing a second or later clinical relapse at the time of their diagnosis. Overall, the average time between symptom onset and diagnosis was 4.4 months throughout the total group.

Of the 77 instances of DD, 42 (28.7%) occurred at the hands of physicians, 22 of which were due to misdiagnosis by a neurologist. Other determinants included incorrect symptom classifications and failures to complete or interpret diagnostic workups. Patient-dependent DD occurred in 35 (24%) of cases and were largely attributed to delays in medical consultations because symptoms were mild (n = 19).

The researchers’ analysis revealed associations between a longer DD and higher EDSS (P = .046), higher CSF-NfL levels (P = .046; n = 76), more total lesions (P = .025), and greater infratentorial lesion volume (P = .034) at the time of a patient’s diagnosis. In a similar trend, those with histories of more than 1 relapse at diagnosis (n = 63; 43.2%) exhibited higher EDSS scores (P = .006) and total (P = .04) and periventricular (P = .039) brain lesions compared with patients who received a diagnosis at their first clinical relapse.

The authors concluded, “Considering the consequences of initiating DMT late, reducing DDs of MS should be a priority. Physician-dependent DDs are often determined by neurologists; therefore, educational efforts that focus on common differential diagnostic issues in MS patients, including misdiagnosis of peripheral syndromes, might improve the diagnostic accuracy. Public awareness campaigns could increase early recognition of MS symptoms and motivate visits to health care providers.”

Reference

Uher T, Adzima A, Srpova B, et al. Diagnostic delay of multiple sclerosis: prevalence, determinants and consequences. Mult Scler. 2023;29(11-12):1437-1451. doi: 10.1177/13524585231197076