Pathogenesis – Medicom Eduction

In a large retrospective real-world analysis, process mining and deep learning techniques were applied to characterise patient trajectories associated with delayed MS diagnosis. The findings identified substantial disparities in time to diagnosis, driven by gaps in early recognition, insurance-related barriers, and variability in referral and treatment pathways.

Early intervention in MS is essential, as prompt initiation of disease-modifying therapy (DMT) reduces relapse frequency, delays disability progression, and improves long-term neurological outcomes. Dr Arjun Gurjar (University of California, CA, USA) and colleagues therefore sought to quantify critical disparities in the MS diagnostic timeline and determine whether insurance claims could be used to model diagnostic trajectories and identify drivers of delay [1].

The investigators retrospectively analysed a cohort of 447,222 MS patients, using the Komodo Health longitudinal claims dataset, the largest cohort to date analysed for modelling MS healthcare trajectories. An open-source electronic health records (EHR) foundation model was used to generate patient-level embeddings that capture longitudinal healthcare interactions. These embeddings were subsequently clustered to identify subgroups characterised by diagnostic delay, referral sequences, and comorbidity-related confounding.

The analysis demonstrated marked disparities in diagnostic timelines across healthcare entry points. Patients entering the healthcare system through emergency medicine experienced the longest time to MS diagnosis, followed by those referred by general practitioners. In contrast, direct entry via neurology rendered the shortest diagnostic interval.

The authors hypothesised that several mechanisms may contribute to these delays. Misdiagnosis appears to be common, with early MS symptoms frequently attributed to psychiatric, orthopaedic, or rheumatologic conditions. Geographic and structural barriers, described as a “desert phenomenon”, reflecting limited access to specialist care, may further prolong time to diagnosis. Emergency department data suggested additional contributors: patients presenting with demyelination symptoms often did not undergo appropriate MS diagnostic workups, with CT performed instead of MRI scans. Additionally, individuals with prodromal cognitive symptoms were frequently managed within psychiatric channels prior to neurological evaluation.

Together, these findings highlight the need for improved early recognition strategies, streamlined referral pathways, and equitable access to specialist care to reduce diagnostic delays and optimise outcomes in MS.

Gurjar A, et al. A claims-based analysis of 447,222 MS patients: Revealing pre-diagnostic trajectories with process mining and representation learning. P403, ACTRIMS Congress 2026, 4–7 February, San Diego, California, USA.

Using population-based laboratory and health claims data from Ontario, Canada (2007–2022), investigators identified cases suggesting that MS onset may precede documented primary Epstein-Barr virus (EBV) infection.

Among 95,980 individuals with laboratory-confirmed primary EBV infection, 300 (0.31%) had ≥3 MS diagnostic codes at any time. Within this subgroup, 74 patients (24.7%) had at least 1 demyelinating disease code preceding the index EBV-positive test. The mean age at MS onset in these cases was 33.3 years (SD 14.3), and 56 (75.7%) were women. Notably, 58 of the 74 patients (78.4%) fulfilled a validated MS case definition (3 MS diagnostic codes) prior to their first documented EBV-positive test.

“These findings question whether EBV infection is required in all cases for the development of MS,” said Dr Dalia Rotstein (University of Toronto, ON, Canada) [1]. The study was motivated by 3 key questions:

Is EBV infection a requisite environmental exposure for MS to develop?
Is EBV causally related to MS pathogenesis?
Could EBV seronegativity be used to exclude an MS diagnosis?

Dr Rotstein emphasised the importance of avoiding the post hoc, ergo hoc fallacy: “Although nearly all individuals with MS have evidence of prior EBV infection, this temporal association alone does not establish causality.”

The investigators concluded that, at a population level, cases of MS onset preceding documented EBV infection can be identified, and these were not limited to clinically isolated syndrome (CIS) or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD).

Potential explanations include MS misdiagnosis, misclassification of EBV infection (e.g., false-positive or delayed testing), EBV reactivation rather than primary infection, or the possibility that alternative infectious triggers, such as human herpes virus (HHV-6), may contribute to MS pathogenesis. Further research is warranted to clarify these observations and their implications for understanding MS causality.

Rotstein DL, et al. Is it possible for MS onset to precede EBV infection? A population-based assessment. CE2.2, ACTRIMS Congress 2026, 4–7 February, San Diego, California, USA.

Critical disparities in the diagnostic timeline of MS quantified

Is Epstein-Barr virus infection not a prerequisite for MS?