The following is a summary of “Association of NOTCH3 Variant Risk Category With 2-Year Clinical and Radiologic Small Vessel Disease Progression in Patients With CADASIL,” published in the May 2024 issue of Neurology by Cerfontaine et al.
Researchers conducted a retrospective study to investigate the association between the NOTCH3 variant risk category and the two-year progression of clinical and neuroimaging markers of small vessel disease (SVD) in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).
They involved patients with CADASIL. Clinical assessments included incident stroke, disability (measured by modified Rankin Scale), and executive function (evaluated using Trail Making Test B and given as T-scores). Neuroimaging parameters comprised mean skeletonized mean diffusivity (MSMD), normalized white matter hyperintensity volume (nWMHv), normalized lacune volume (nLV), and brain parenchymal fraction (BPF). Employing Cox regression and mixed-effect models adjusted for age, sex, and cardiovascular risk factors, they assessed 2-year outcome changes and progression differences in HR-NOTCH3 and MR-NOTCH3 variants.
The results showed 162 patients with high-risk (HR) (n = 90), moderate-risk (MR) (n = 67), and low-risk (LR) (n = 5) NOTCH3 variants were included. Across the cohort, there was a 2-year mean progression for MSMD (β = 0.20, 95% CI 0.17–0.23, P=7.0 × 10-24), nLV (β = 0.13, 95% CI 0.080–0.19, P=2.1 × 10-6), nWMHv (β = 0.092, 95% CI 0.075–0.11, P=8.8 × 10-20), and BPF (β = −0.22, 95% CI −0.26 to −0.19, P=3.2 × 10-22), along with increased disability (P=0.002) and declined executive function (β = −0.15, 95% CI −0.30 to −3.4 × 10-5, P=0.05). The HR-NOTCH3 group exhibited a higher probability of 2-year incident stroke (HR 4.3, 95% CI 1.4–13.5, P=0.011), along with increased MSMD (β = 0.074, 95% CI 0.013–0.14, P=0.017) and nLV (β = 0.14, 95% CI 0.034–0.24, P=0.0089) compared to the MR-NOTCH3 group. Subgroup analyses revealed significant 2-year progression of MSMD in young (n = 17, β = 0.014, 95% CI 0.0093–0.019, P=1.4 × 10-5) and premanifest (n = 24, β = 0.012, 95% CI 0.0082–0.016, P=1.1 × 10-6) individuals.
Investigators concluded that HR-NOTCH3 variants predicted faster progression of SVD in patients with CADASIL over two years, highlighting their potential role in clinical trials and disease management.
Source: neurology.org/doi/10.1212/WNL.0000000000209310
