Microbleed clustering in thalamus sign in CADASIL patients with NOTCH3 R75P mutation.

Background and objective: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral microvascular disease characterized by the development of vascular dementia and lacunar infarctions. This study aimed to identify the genetic and clinical features of CADASIL in Japan. Methods: We conducted genetic analysis on a case series of patients clinically diagnosed with CADASIL. Clinical and imaging analyses were performed on 32 patients with pathogenic mutations in the NOTCH3 gene. To assess the presence of cerebral microbleeds (CMBs), we utilized several established rating scales including the Fazekas scale, Scheltens rating scale, and Microbleed Anatomical Rating Scale, based on brain MRI images. Results: Among the 32 CADASIL patients, 24 cases were found carrying the R75P mutation in NOTCH3, whereas the remaining eight cases had other NOTCH3 mutations (R75Q, R110C, C134F, C144F, R169C, and R607C). The haplotype analysis of the R75P mutation uncovered the presence of a founder effect. A brain MRI analysis revealed that cases with the R75P mutation had a significantly higher total number of CMBs, particularly in the thalamus when compared to patients with other NOTCH3 mutations. Among 15 out of 24 cases with the R75P mutation, we observed a notable clustering of CMBs in the thalamus, termed microbleed clustering in thalamus sign (MCT sign). Conclusion: We propose that the MCT sign observed in NOTCH3 R75P-related CADASIL patients may serve as a potentially characteristic imaging feature. This finding offers further insights into the interactions between genotypes and phenotypes between NOTCH3 and CADASIL.

[Case of juvenile parkinsonism in pregnancy].

A 29-year-old woman with two sons developed a rest tremor and motor slowness in her right limbs. She was diagnosed as Parkinson's disease (PD) and was treated with anti-cholinergic drugs. After three years of taking a dopamine agonist (cabergoline, 4 mg per day), she became pregnant. The patient and her husband decided to have an abortion because they worried that the cabergoline might have harmed the fetus. The patient hoped to prepare for future planned birth, so we canceled the cabergoline and gradually increased her carbidopa/levodopa dose. Her motor disability gradually worsened during the pregnancy, and she developed prominent bradykinesia while taking a high dose of carbidopa/levodopa (1,000 mg per day) and a continuous infusion of levodopa. A cesarean section was performed, and the patient gave birth to a healthy baby. After the delivery, she was treated with pramipexole (2 mg per day), and her bradykinesia decreased. The initial anti-PD medication schedule for fertile female PD patients should be carefully considered to lessen the harm to the fetus, especially during organogenesis. Motor disability may worsen during pregnancy, and appropriate childcare support should be prepared.