Yoshio Sakiyama

Publications (5)8.52 Total impact

• Article: Spinocerebellar ataxia type 2 is associated with Parkinsonism and Lewy body pathology.

  Masaki Takao, Masahiro Aoyama, Kinya Ishikawa, Yoshio Sakiyama, Harumi Yomono, Yuko Saito, Hiroshi Kurisaki, Ban Mihara, Shigeo Murayama
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  ABSTRACT: Clinical phenotype of individuals with spinocerebellar ataxia 2 (SCA2) is characterised by cerebellar ataxia and cognitive impairment. Although L-dopa-responsive Parkinsonism is considered as a rare clinical presentation in SCA2, it has been brought to the attention of many neurologists in several studies. The authors report an autopsy case of SCA2 with Parkinsonism from a Japanese family using archival materials of our Brain Bank to describe unique neuropathologic findings. The individual clinically showed Parkinsonism as a predominant phenotype instead of cerebellar ataxia. Besides the classic SCA2 neuropathologic alterations, Lewy bodies and Lewy neurites were present in the brainstem nuclei. Genetic analysis revealed shorter abnormal expansion of CAG repeats (less than 39). In contrast, the authors could not find α-synuclein pathology in two SCA2 cases without Parkinsonism. The present case will provide a neuropathologic evidence of correlation between α-synucleinopathy and Parkinsonism of SCA2 as well as shed light on understanding the pathomechanism of Parkinsonism in SCA2.
  Case Reports 01/2011; 2011.
• Article: [Autopsy case of SCA2 with Parkinsonian phenotype].

  Harumi S Yomono, Hiroshi Kurisaki, Akira Hebisawa, Yoshio Sakiyama, Yuko Saito, Shigeo Murayama
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  ABSTRACT: This is the first autopsy case of SCA2 with parkinsonian phenotype. At the age of 46, the patient got symptoms of parkinsonism to which anti-parkinsonian drugs were effective. He had mosaic 38, 40 CAG repeat expansions on chromosome 12q23-24, being diagnosed as SCA2, and his mother and his son also had CAG expansions on the same locus. In addition to parkinsonism, he also exhibited autonomic disturbance, dementia, and mild cerebellar ataxia Brain images revealed severe atrophy of pons and medulla oblongata, resembling MSA-C. HVA and 5-HIAA were reduced in the cerebrospinal fluid, and the heart-mediastinum (H/M) ratio in myocardial 123I-MIBG cintigram was decreased, which suggested Lewy body pathology. He died at the age of 75 and the autopsy revealed atrophy of the olivo-ponto-cerebellar (OPC) system and substantia nigra which was compatible to SCA2, although the OPC system atrophy was less severe than formerly reported SCA2 cases. The degrees of atrophy of the OPC system and substantia nigra might explain the predominancy of clinical symptoms. Anti-1C2 positive inclusions in the pontine nuclei, inferior olive nuclei, cerebellum and substantia nigra confirmed a polyglutamine disease. In addition, there were the anti-phosphorylated alpha-synuclein positive, Lewy body related pathological changes in the substantia nigra, the locus ceruleus, the dorsal motor nuclei of vagus, and the sympathetic nerve in the myocardium. Major genetic abnormalities related to Parkinson disease were not detected. As another case of SCA2 with Lewy body pathology was reported in Japan, the coexistence of SCA2 and Lewy body pathology may not be accidental. Since myocardial MIBG scincigram can predict Lewy body pathology, we should seek more clinical cases of SCA2 with Lewy body pathology.
  Rinsho shinkeigaku = Clinical neurology 03/2010; 50(3):156-62.
• Article: Incidence and extent of Lewy body-related alpha-synucleinopathy in aging human olfactory bulb.

  Renpei Sengoku, Yuko Saito, Masako Ikemura, Hiroyuki Hatsuta, Yoshio Sakiyama, Kazutomi Kanemaru, Tomio Arai, Motoji Sawabe, Noriko Tanaka, Hideki Mochizuki, Kiyoharu Inoue, Shigeo Murayama
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  ABSTRACT: We investigated the incidence and extent of Lewy body (LB)-related alpha-synucleinopathy (LBAS) in the olfactory bulb (OB) in 320 consecutive autopsy patients from a general geriatric hospital (mean age, 81.5 +/- 8.5 years). Paraffin sections were immunostained with anti-phosphorylated alpha-synuclein, tyrosine hydroxylase, phosphorylated tau, and amyloid beta antibodies. LBAS was found in 102 patients (31.9%) in the central nervous system, including the spinal cord; the OB was involved in 85 (26.6%). Among these 85 patients, 2 had LBAS only in the anterior olfactory nucleus, 14 in the peripheral OB only, and 69 in both areas. In 5 patients, Lewy bodies were found only in the OB by hematoxylin and eosin stain; 3 of these patients had Alzheimer disease, and all had LBAS. Very few tyrosine hydroxylase-immunoreactive periglomerular cells exhibited LBAS. All 35 LBAS patients with pigmentation loss in the substantia nigra had LBAS in the OB. LBAS in the amygdala was more strongly correlated with LBAS in the anterior olfactory nucleus than with that in the OB periphery. LBAS did not correlate with systemic tauopathy or amyloid beta amyloidosis. These results indicate a high incidence of LBAS in the aging human OB; they also suggest that LBAS extends from the periphery to the anterior olfactory nucleus and results in clinical manifestations of LB disease.
  Journal of Neuropathology and Experimental Neurology 12/2008; 67(11):1072-83. · 4.26 Impact Factor
• Article: Lewy body pathology involves cutaneous nerves.

  Masako Ikemura, Yuko Saito, Renpei Sengoku, Yoshio Sakiyama, Hiroyuki Hatsuta, Kazutomi Kanemaru, Motoji Sawabe, Tomio Arai, Genta Ito, Takeshi Iwatsubo, Masashi Fukayama, Shigeo Murayama
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  ABSTRACT: Involvement of the peripheral autonomic nervous system is a core feature of Lewy body (LB) diseases, including Parkinson disease (PD), PD with dementia, and dementia with LBs. To investigate the potential use of skin biopsy for the diagnosis of LB diseases, we assessed anti-phosphorylated alpha-synuclein immunoreactivity in peripheral nerves in samples of skin from the abdominal wall and flexor surface of the upper arm in 279 prospectively studied consecutively autopsied patients whose data were registered at the Brain Bank for Aging Research between 2002 and 2005. Positive immunoreactivity was demonstrated in the unmyelinated fibers of the dermis in 20 of 85 patients with LB pathology in the CNS and the adrenal glands, the latter representing a substitute for peripheral autonomic nervous system sympathetic ganglia; no reactivity was seen in 194 patients without CNS LB pathology. In 142 retrospectively studied patients autopsied from 1995 onward who had subclinical or clinical LB disease, the sensitivity of the positive skin immunoreactivity was 70% in PD and PD with dementia and 40% in dementia with LBs. Skin immunoreactivity was absent in cases of multiple-system atrophy, progressive nuclear palsy, and corticobasal degeneration. We demonstrate for the first time that the skin is involved and may be a highly specific and useful biopsy site for the pathological diagnosis of LB diseases.
  Journal of Neuropathology and Experimental Neurology 10/2008; 67(10):945-53. · 4.26 Impact Factor
• Article: [Neuropathological diagnosis of prion disease].

  Shigeo Murayama, Yuko Saito, Hiroyuki Hatsuta, Yoshio Sakiyama
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  ABSTRACT: Neuropathological diagnosis of prion disease consists of sequence analysis of PRNP (prion protein gene), located on chromosome 20 and characterization and visualization of deposited proteinase K-resistant prion protein (PrP(Sc)). SNP at 129 locus (M/V) and Type 1 and Type 2 difference in Western blot analysis of PrP(Sc) from the postmortem brain influence the clinical and pathological presentations. Prion disease is classified into sporadic, hereditary and infectious subtypes, but PrP(Sc) from almost all the subtypes can transmit the disease to transgenic mice expressing human PRNP. Variant CJD, apparently derived from bovine spongiformic encephalopathy, requires shift in disease control strategy, in that PrP(Sc) is present in peripheral lymphatic organs.
  Nippon rinsho. Japanese journal of clinical medicine 09/2007; 65(8):1401-6.