Rinsho Shinkeigaku (Clinical Neurology)

Case Report

CADASIL with cysteine-sparing NOTCH3 mutation manifesting as dissociated progression between cognitive impairment and brain image findings in 3 years: A case report

Keisuke Tachiyama, M.D.1)3), Yuji Shiga, M.D.1)4), Yutaka Shimoe, M.D., Ph.D.1), Ikuko Mizuta, M.D., Ph.D.2), Toshiki Mizuno, M.D., Ph.D.2) and Masaru Kuriyama, M.D., Ph.D.1)

1)Department of Neurology, Brain Attack Center, Ota Memorial Hospital
2)Department of Neurology, Kyoto Prefectural University of Medicine
3)Present address: Hiroshima City Hiroshima Citizens Hospital
4)Present address: Hiroshima University Graduate School of Biomedical and Health Sciences

A 55-year-old man with no history of stroke or migraine presented to the clinic with cognitive impairment and depression that had been experiencing for two years. Neurological examination showed bilateral pyramidal signs, and impairments in cognition and attention. Brain MRI revealed multiple lacunar lesions and microbleeds in the deep cerebral white matter, subcortical regions, and brainstem, as well as diffuse white matter hyperintensities without anterior temporal pole involvement. Cerebral single-photon emission computed tomography (SPECT) revealed bilateral hypoperfusion in the basal ganglia. Gene analysis revealed an arginine-to-proline missense mutation in the NOTCH3 gene at codon 75. The patient was administered lomerizine (10 mg/day), but the patient's cognitive impairment and cerebral atrophy continued to worsen. Follow-up testing with MRI three years after his initial diagnosis revealed similar lacunar infarctions, cerebral microbleeds, and diffuse white matter hyperintensities to those observed three years earlier. However, MRI scans revealed signs of increased cerebral blood flow. Together, these findings suggest that the patient's cognitive impairments may have been caused by pathogenesis in the cerebral cortex.
Full Text of this Article in Japanese PDF (967K)

(CLINICA NEUROL, 58: 235|240, 2018)
key words: CADASIL, cysteine-sparing NOTCH3 mutation, dementia, lomerizine

(Received: 22-Dec-17)