Prevalence of CADASIL and Fabry Disease in a Cohort of MRI Defined Younger Onset Lacunar Stroke.

BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), caused by mutations in the NOTCH3 gene, is the most common monogenic disorder causing lacunar stroke and cerebral small vessel disease (SVD). Fabry disease (FD) due to mutations in the GLA gene has been suggested as an underdiagnosed cause of stroke, and one feature is SVD. Previous studies reported varying prevalence of CADASIL and FD in stroke, likely due to varying subtypes studied; no studies have looked at a large cohort of younger onset SVD. We determined the prevalence in a well-defined, MRI-verified cohort of apparently sporadic patients with lacunar infarct. METHODS: Caucasian patients with lacunar infarction, aged ≤70 years (mean age 56.7 (SD8.6)), were recruited from 72 specialist stroke centres throughout the UK as part of the Young Lacunar Stroke DNA Resource. Patients with a previously confirmed monogenic cause of stroke were excluded. All MRI's and clinical histories were reviewed centrally. Screening was performed for NOTCH3 and GLA mutations. RESULTS: Of 994 subjects five had pathogenic NOTCH3 mutations (R169C, R207C, R587C, C1222G and C323S) all resulting in loss or gain of a cysteine in the NOTCH3 protein. All five patients had confluent leukoaraiosis (Fazekas grade ≥2). CADASIL prevalence overall was 0.5% (95% CI 0.2%-1.1%) and among cases with confluent leukoaraiosis 1.5% (95% CI 0.6%-3.3%). No classic pathogenic FD mutations were found; one patient had a missense mutation (R118C), associated with late-onset FD. CONCLUSION: CADASIL cases are rare and only detected in SVD patients with confluent leukoaraiosis. No definite FD cases were detected.

Plaque formation and removal assessed in vivo in a novel repeated measures imaging methodology.

OBJECTIVE: A repeated measures digital imaging technique (Digital Plaque Image Analysis) was used to assess variations in plaque formation, including levels of plaque developed following evening and morning tooth brushing with a standard dentifrice, to establish a baseline for future assessments of antimicrobial formulations. METHODOLOGY: Following a rigorous oral hygiene period, subjects were provided with a standard commercial (non-antibacterial) dentifrice and manual toothbrush and instructed to brush b.i.d., as normal. On six separate days over two weeks, subjects reported at three times for a daily plaque assessment: in the morning before oral hygiene, post-brushing, and in the afternoon post-brushing. RESULTS: Morning plaque levels covered approximately 10% of the measured dentition, and plaque was removed by 75% with morning tooth brushing. Plaque underwent rapid regrowth during the day, and averaged approximately 7% coverage by the afternoon. CONCLUSION: These results support the value of Digital Plaque Image Analysis in recording diurnal plaque variations and treatment effects, and suggest that assessment of oral hygiene efficacy (either mechanical or chemopreventive) accounts for diurnal variations in plaque formation. In addition, the results suggest that plaque regrowth and virulence activity overnight is a significant target for oral hygiene interventions.