Abstract DP231: Prevalence of Multiple Sclerosis Misdiagnosis in CADASIL Across EGFR Domain Risk Categories: A Retrospective Cohort Study

Background: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) can be misdiagnosed as multiple sclerosis (MS). This study aims to contrast demographic, clinical, neuroimaging, and genetic features of CADASIL patients with vs. without prior MS misdiagnosis. Methods: We conducted a retrospective cohort study to compare genetically or histopathologically confirmed CADASIL patients with and without a prior MS misdiagnosis across Mayo Clinic. Patients were classified into high-, medium-, low-, or unknown-risk by location of NOTCH3 mutation. Disease severity was assessed using NOTCH3 Small-Vessel Disease (N3SVD) scale. Between-group comparisons used independent t-test for age, chi-square or Fisher’s exact test for categorical variables, and Mann–Whitney U test for quantitative variables. Within the misdiagnosed subgroup, neuroimaging changes between MS to CADASIL diagnosis were assessed using Wilcoxon signed-rank test for quantitative data and Stuart–Maxwell test for categorical data. Significance was set at p<0.05 (two-sided). Results: Among 107 patients (mean age 57.5±13.4 yrs) with CADASIL, 12 (11.2%) had a prior MS misdiagnosis (Table 1). Compared to patients without misdiagnosis (n=95), those misdiagnosed were younger, more frequently Asian, more likely to undergo lumbar puncture (83.3% vs 26.3%, p <0.001), and less likely to have had stroke (33.3% vs 65.3%, p =0.031). There were no significant differences in deep white matter hyperintensity scores or lacune counts. However, the misdiagnosed group had a higher median modified Rankin Scale ( p =0.008) and a different distribution of N3SVD stages ( p =0.017), with a higher proportion in stage 3A (33.3% vs 5.3%). There was no significant difference in genetic risk categories (Figure), but 5 of 12 misdiagnosed cases clustered in the medium risk EGFR 13, 13.5, and 14 domains. Among the misdiagnosed, 41.7% received MS-specific treatment during a median of 10.2 months (range 0.4–138.1) before diagnostic correction (Table 2). Over this period, there were no significant changes in DWMH score, lacune count, mRS, or N3SVD stage (all p >0.05). Conclusions: About one in nine CADASIL patients had a prior MS diagnosis. Atypical presentations in younger individuals without a clear stroke history may prompt consideration of MS over CADASIL, leading to diagnostic delays and unnecessary treatments. EGFR domain risk category did not correlate with misdiagnosis.