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March 16, 2011

Skin biopsy is useful for the antemortem diagnosis of neuronal intranuclear inclusion disease

April 19, 2011 issue
76 (16) 1372-1376

Abstract

Background:

Neuronal intranuclear inclusion disease (NIID) is a progressive neurodegenerative disease characterized by eosinophilic hyaline intranuclear inclusions in neuronal and somatic cells. Because of the variety of clinical manifestations, antemortem diagnosis of NIID is difficult.

Methods:

Seven skin biopsy samples from patients with familial NIID were evaluated histochemically, and the results were compared with those of skin samples from normal control subjects and from patients with other neurologic diseases. We also examined skin biopsy samples from patients with NIID by electron microscopy.

Results:

In NIID skin biopsy samples, intranuclear inclusions were observed in adipocytes, fibroblasts, and sweat gland cells. These inclusions were stained with both anti-ubiquitin and anti-SUMO1 antibodies. Electron microscopy revealed that the features of the intranuclear inclusions in adipocytes, fibroblasts, and sweat gland cells were identical to those of neuronal cells. Approximately 10% of adipocytes showed intranuclear inclusions. No intranuclear inclusions were identified in the skin samples from normal control subjects and patients with other neurologic diseases.

Conclusions:

Skin biopsy is an effective and less invasive antemortem diagnostic tool for NIID.

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Information & Authors

Information

Published In

Neurology®
Volume 76Number 16April 19, 2011
Pages: 1372-1376
PubMed: 21411744

Publication History

Received: August 6, 2010
Accepted: November 17, 2010
Published online: March 16, 2011
Published in print: April 19, 2011

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Disclosure

Dr. Sone reports no disclosures. Dr. Tanaka has received research support from the Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (21659221, 22390175), and a grant from the Ministry of Health, Welfare and Labor of Japan. Dr. Koike has received research support from the Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (21591076), and a grant from the Ministry of Health, Welfare and Labor of Japan. Dr. Inukai reports no disclosures. Dr. Katsuno received research support from the Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (21689024, 2110005). Dr. Yoshida received research support from the Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (21500339), and a grant from the Ministry of Health, Welfare and Labor of Japan. Dr. Watanabe reports no disclosures. Dr. Sobue serves on scientific advisory boards for Kanae Science Foundation for the Promotion of Medical Science, Naito Science Foundation, and has received research support from the Ministry of Education, Culture, Sports, Science and Technology of Japan (21229011, 17025020, 09042025), the Ministry of Welfare, Health and Labor of Japan, and the Japan Science and Technology Agency, Core Research for Evolutional Science and Technology.

Authors

Affiliations & Disclosures

J. Sone, MD, PhD
From the Department of Neurology (J.S., F.T., H.K., H.W., G.S.), Nagoya University Graduate School of Medicine, Nagoya; Department of Neurology (A.I.), National Hospital Organization Higashi Nagoya National Hospital, Nagoya; Institute for Advanced Research (M.K.), Nagoya University, Nagoya; and Department of Neuropathology (M.Y.), Institute for Medical Sciences of Aging, Aichi Medical University, Aichi, Japan.
F. Tanaka, MD, PhD
From the Department of Neurology (J.S., F.T., H.K., H.W., G.S.), Nagoya University Graduate School of Medicine, Nagoya; Department of Neurology (A.I.), National Hospital Organization Higashi Nagoya National Hospital, Nagoya; Institute for Advanced Research (M.K.), Nagoya University, Nagoya; and Department of Neuropathology (M.Y.), Institute for Medical Sciences of Aging, Aichi Medical University, Aichi, Japan.
H. Koike, MD, PhD
From the Department of Neurology (J.S., F.T., H.K., H.W., G.S.), Nagoya University Graduate School of Medicine, Nagoya; Department of Neurology (A.I.), National Hospital Organization Higashi Nagoya National Hospital, Nagoya; Institute for Advanced Research (M.K.), Nagoya University, Nagoya; and Department of Neuropathology (M.Y.), Institute for Medical Sciences of Aging, Aichi Medical University, Aichi, Japan.
A. Inukai, MD, PhD
From the Department of Neurology (J.S., F.T., H.K., H.W., G.S.), Nagoya University Graduate School of Medicine, Nagoya; Department of Neurology (A.I.), National Hospital Organization Higashi Nagoya National Hospital, Nagoya; Institute for Advanced Research (M.K.), Nagoya University, Nagoya; and Department of Neuropathology (M.Y.), Institute for Medical Sciences of Aging, Aichi Medical University, Aichi, Japan.
M. Katsuno, MD, PhD
From the Department of Neurology (J.S., F.T., H.K., H.W., G.S.), Nagoya University Graduate School of Medicine, Nagoya; Department of Neurology (A.I.), National Hospital Organization Higashi Nagoya National Hospital, Nagoya; Institute for Advanced Research (M.K.), Nagoya University, Nagoya; and Department of Neuropathology (M.Y.), Institute for Medical Sciences of Aging, Aichi Medical University, Aichi, Japan.
M. Yoshida, MD, PhD
From the Department of Neurology (J.S., F.T., H.K., H.W., G.S.), Nagoya University Graduate School of Medicine, Nagoya; Department of Neurology (A.I.), National Hospital Organization Higashi Nagoya National Hospital, Nagoya; Institute for Advanced Research (M.K.), Nagoya University, Nagoya; and Department of Neuropathology (M.Y.), Institute for Medical Sciences of Aging, Aichi Medical University, Aichi, Japan.
H. Watanabe, MD, PhD
From the Department of Neurology (J.S., F.T., H.K., H.W., G.S.), Nagoya University Graduate School of Medicine, Nagoya; Department of Neurology (A.I.), National Hospital Organization Higashi Nagoya National Hospital, Nagoya; Institute for Advanced Research (M.K.), Nagoya University, Nagoya; and Department of Neuropathology (M.Y.), Institute for Medical Sciences of Aging, Aichi Medical University, Aichi, Japan.
G. Sobue, MD, PhD
From the Department of Neurology (J.S., F.T., H.K., H.W., G.S.), Nagoya University Graduate School of Medicine, Nagoya; Department of Neurology (A.I.), National Hospital Organization Higashi Nagoya National Hospital, Nagoya; Institute for Advanced Research (M.K.), Nagoya University, Nagoya; and Department of Neuropathology (M.Y.), Institute for Medical Sciences of Aging, Aichi Medical University, Aichi, Japan.

Notes

Address correspondence and reprint requests to Dr. Fumiaki Tanaka, Department of Neurology, Nagoya University Graduate School of Medicine, 65, Tsurumai-cho, Shouwa-ku, Nagoya, Aichi 466-8550, Japan [email protected]
Study funding: Supported by a 21st Century Center of Excellence (COE) grant and a global COE grant from the Ministry of Education, Culture, Sports, Science and Technology of Japan and by a grant from the Ministry of Health, Welfare and Labor of Japan.

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