Neurogenetic Evaluation Identifies Misdiagnosis in Individuals with Atypical MS

Increased access to broad-based next generation sequencing could strengthen differential diagnosis in cases of “atypical” multiple sclerosis (MS), according to study results presented at the 40th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Although many adult-onset genetic leukoencephalopathies (gLes) share clinical and radiographic characteristics with MS, gLes are not often considered in the differential diagnosis.

Researchers performed a blinded, retrospective review of the medical records of 61 patients with “atypical” MS, defined as having a prior MS diagnosis referred for neurogenetic evaluation between 2015 and 2022. They compared first available neuroimaging with most recent neuroimaging for each patient to assess if these individuals met 2017 McDonald Criteria for relapsing-remitting (RR) or primary progressive (PP) MS and if the patients exhibited historical or radiographic “red flag” features of MS.

• 25 patients were diagnosed with RRMS, 35 with PPMS, and 1 with radiologically isolated syndrome.
• Only 28% of RRMS patients and 21% of PPMS patients met 2017 McDonald criteria.
• The most common radiographic “red flags” included lesion confluence (37.9%), corpus callosal thinning (37.9%), lesion symmetry (19.0%), and anterior temporal lobe and external capsule T2 hyperintensities (19.0%).
• The most common historical “red flags” included positive family history (34.4%), onset after age 50 (13.1%), extrapyramidal signs (13.1%), and isolated progressive myelopathy (11.5%).

The following gLEs were identified in 5 patients: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (N=2), KIF1A disorder, spastic paraplegia type 7, and MERRF-like syndrome.