□
PICTURES IN CLINICAL MEDICINE
□
Skin Biopsy-based Diagnosis of CADASIL with Atypical MRI Findings Yoichiro Nishida 1,2, Akihiko Ueda 3, Yukio Ando 3 and Tadashi Ichikawa 1,2 Key words: anterior temporal pole, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), external capsule, NOTCH3, MRI, skin biopsy (Intern Med 54: 537-538, 2015) (DOI: 10.2169/internalmedicine.54.3350)
Picture. １
Department of Neurology, Saitama Prefectural Rehabilitation Center, Japan, ２Department of Neurology, Kuki General Hospital, Japan and ３Department of Neurology, Graduate School of Medical Sciences Kumamoto University, Japan Received for publication May 23, 2014; Accepted for publication August 5, 2014 Correspondence to Dr. Yoichiro Nishida, [email protected]
537
Intern Med 54: 537-538, 2015
DOI: 10.2169/internalmedicine.54.3350
A 37-year-old man whose father had died after a third stroke at 53 years of age and whose grandfather had died of cerebral infarction in his 40’s underwent brain MRI due to a headache. He had no history of symptomatic stroke; however, the MRI examination showed white matter lesions on FLAIR images (Picture). Although neither the temporopolar white matter nor external capsule, characteristic sites of lesions in cases of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) (1), were clearly involved, the patient’s family history prompted an examination for CADASIL. Consequently, no mutations were found in NOTCH3 exon 3 or 4, where pathogenic mutations are often detected in Japanese patients with CADASIL. In contrast, a skin biopsy revealed typical findings of CADASIL (Supplementary material) (2), and further genetic analyses of the NOTCH3 gene disclosed the p.R332C mutation in exon 6. Although further studies are needed, conducting skin biopsies is worthwhile in pa-
tients with symptoms clinically suspicious of CADASIL, even if the MRI findings are not typical. The authors state that they have no Conflict of Interest (COI). Acknowledgement Authors thank Dr. Akihito Nagatoshi for performing the gene analysis and Dr. Hidenobu Matsumoto for conducting the electron microscopic analysis.
References 1. O’Sullivan M, Jarosz JM, Martin RJ, Deasy N, Powell JF, Markus HS. MRI hyperintensities of the temporal lobe and external capsule in patients with CADASIL. Neurology 56: 628-634, 2001. 2. Ueda A, Hirano T, Takahashi K, et al. Detection of granular osmiophilic material of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy by light microscopy in frozen sections. Neuropathol Appl Neurobiol 35: 618-622, 2009.
Ⓒ 2015 The Japanese Society of Internal Medicine http://www.naika.or.jp/imonline/index.html
538
PICTURES IN CLINICAL MEDICINE
□
Skin Biopsy-based Diagnosis of CADASIL with Atypical MRI Findings Yoichiro Nishida 1,2, Akihiko Ueda 3, Yukio Ando 3 and Tadashi Ichikawa 1,2 Key words: anterior temporal pole, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), external capsule, NOTCH3, MRI, skin biopsy (Intern Med 54: 537-538, 2015) (DOI: 10.2169/internalmedicine.54.3350)
Picture. １
Department of Neurology, Saitama Prefectural Rehabilitation Center, Japan, ２Department of Neurology, Kuki General Hospital, Japan and ３Department of Neurology, Graduate School of Medical Sciences Kumamoto University, Japan Received for publication May 23, 2014; Accepted for publication August 5, 2014 Correspondence to Dr. Yoichiro Nishida, [email protected]
537
Intern Med 54: 537-538, 2015
DOI: 10.2169/internalmedicine.54.3350
A 37-year-old man whose father had died after a third stroke at 53 years of age and whose grandfather had died of cerebral infarction in his 40’s underwent brain MRI due to a headache. He had no history of symptomatic stroke; however, the MRI examination showed white matter lesions on FLAIR images (Picture). Although neither the temporopolar white matter nor external capsule, characteristic sites of lesions in cases of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) (1), were clearly involved, the patient’s family history prompted an examination for CADASIL. Consequently, no mutations were found in NOTCH3 exon 3 or 4, where pathogenic mutations are often detected in Japanese patients with CADASIL. In contrast, a skin biopsy revealed typical findings of CADASIL (Supplementary material) (2), and further genetic analyses of the NOTCH3 gene disclosed the p.R332C mutation in exon 6. Although further studies are needed, conducting skin biopsies is worthwhile in pa-
tients with symptoms clinically suspicious of CADASIL, even if the MRI findings are not typical. The authors state that they have no Conflict of Interest (COI). Acknowledgement Authors thank Dr. Akihito Nagatoshi for performing the gene analysis and Dr. Hidenobu Matsumoto for conducting the electron microscopic analysis.
References 1. O’Sullivan M, Jarosz JM, Martin RJ, Deasy N, Powell JF, Markus HS. MRI hyperintensities of the temporal lobe and external capsule in patients with CADASIL. Neurology 56: 628-634, 2001. 2. Ueda A, Hirano T, Takahashi K, et al. Detection of granular osmiophilic material of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy by light microscopy in frozen sections. Neuropathol Appl Neurobiol 35: 618-622, 2009.
Ⓒ 2015 The Japanese Society of Internal Medicine http://www.naika.or.jp/imonline/index.html
538
