Abstract Details

Title Multiple Sclerosis Misdiagnosis in CADASIL: A Genotype-Mis-Phenotype Study

Topic Multiple Sclerosis

Presentation(s) P8 - Poster Session 8 (11:45 AM-12:45 PM)

Poster/Presentation
Number 20-009

Objective

To determine the prevalence of multiple sclerosis (MS) misdiagnosis in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), identify associated clinical and genetic features, and consequences of this diagnostic error.

Background CADASIL can be misdiagnosed as MS due to overlapping clinical and radiological features. This delays appropriate management and exposes patients to unnecessary, potentially harmful MS-directed therapies.

Design/Methods

We conducted a retrospective cohort study to compare genetically or histopathologically confirmed CADASIL patients with and without a prior MS misdiagnosis. Patients were classified into high-, medium-, low-, or unknown-risk by the location of their NOTCH3 variant in the epidermal growth-factor-like repeat (EGFr) domain. Disease severity was assessed using NOTCH3 Small-Vessel Disease (N3SVD) scale. Between-group comparisons used chi-square or Fisher’s exact test for categorical variables, and Mann–Whitney U test for quantitative variables.

Results Of 107 CADASIL patients(mean age 57.5±13.4 yrs), 11(10.2%) were misdiagnosed with MS. Misdiagnosed patients were more frequently Asian (p <0.001), less likely to have a stroke history(36.4% vs 73.8%, p=0.03), and more likely to be diagnosed with CADASIL at an advanced N3SVD disease stage(p=0.010) with higher median mRS scores(p=0.009). The median time to diagnostic correction was 14.45 months(range 1.18–138.07), during which five patients(45.5%) received unnecessary MS therapies and two experienced documented adverse events. Genetic analysis showed a trend towards NOTCH3 mutations in medium-risk EGFr domains(54.5% vs 30.7%, p=0.06), and all misdiagnosed patients treated for MS had mutations outside the classic high-risk 1-6 EGFr domains.

Conclusions

Approximately one in ten patients with CADASIL is initially misdiagnosed as MS, an error associated with Asian race and absence of a stroke history, leading to worse functional outcomes and inappropriate treatments. A high index of suspicion for CADASIL is critical in patients presenting with atypical or late-onset demyelinating disease. Larger studies are needed to understand the role of medium-risk variants in misdiagnosis.

Authors/Disclosures
Sai Krishna Vallamchetla, MBBS (Mayo Clinic, Florida) PRESENTER	Mr. Vallamchetla has nothing to disclose.
Dinith Mendis	Mr. Mendis has nothing to disclose.
Iris V. Marin Collazo, MD (Mayo Clinic)	Dr. Marin Collazo has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG.
Johnny S. Sandhu, MD	Dr. Sandhu has nothing to disclose.
James F. Meschia, MD, FAAN (Mayo Clinic)	The institution of Dr. Meschia has received research support from NINDS. The institution of Dr. Meschia has received research support from NINDS.

��ɫ��

��ɫ��