Faculty Profiles - HASHIZUME Atsushi

Head Lift Exercise Improves Swallowing Dysfunction in Spinal and Bulbar Muscular Atrophy. Reviewed International journal

Tomoo Mano, Masahisa Katsuno, Haruhiko Banno, Keisuke Suzuki, Noriaki Suga, Atsushi Hashizume, Amane Araki, Yasuhiro Hijikata, Seiya Tanaka, Jun Takatsu, Hirohisa Watanabe, Masahiko Yamamoto, Gen Sobue

European neurology Vol. 74 ( 5-6 ) page： 251 - 8 2015

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Dysphagia due to bulbar involvement is a major symptom of patients with spinal and bulbar muscular atrophy (SBMA). The aim of this pilot study was to test the efficacy and safety of the head lift exercise for swallowing dysfunction in SBMA. METHODS: We enrolled 6 subjects with genetically confirmed SBMA and instructed them to perform the head lift exercise for 6 weeks. The efficacy outcome measures were the changes from baseline in tongue pressure, the scores of swallowing functional questionnaires, and the motor functional scales and parameters of videofluorography (VF). RESULTS: All subjects completed the study and no major adverse effects were recorded. Tongue pressure significantly increased by 19.2 ± 0.15% (p < 0.05) after the 6-week head lift exercise. The scores for oral dysphagia also improved, although there was no significant change in VF parameters or other variables examined pre- and post-exercise. CONCLUSION: Our findings suggested that the head lift exercise may improve swallowing dysfunction, particularly tongue pressure, in SBMA.

DOI： 10.1159/000431088

球脊髄性筋萎縮症(SBMA)におけるインスリン抵抗性と運動機能の関連 Reviewed

中辻秀朗, 荒木周, 勝野雅央, 鈴木啓介, 坂野晴彦, 須賀徳明, 橋詰淳, 土方靖浩, 祖父江元

臨床神経学 Vol. 54 ( Suppl. ) page： S150 - S150 2014.12

球脊髄性筋萎縮症におけるlaryngospasmの言語聴覚学的・音響学的検討 Reviewed

田中誠也, 坂野晴彦, 勝野雅央, 鈴木啓介, 須賀徳明, 橋詰淳, 眞野智生, 荒木周, 山本正彦, 祖父江元

臨床神経学 Vol. 54 ( Suppl. ) page： S97 - S97 2014.12

運動ニューロン疾患における耐糖能異常の解析 Reviewed

荒木周, 中辻秀朗, 勝野雅央, 鈴木啓介, 坂野晴彦, 須賀徳明, 橋詰淳, 土方靖浩, 祖父江元

臨床神経学 Vol. 54 ( Suppl. ) page： S198 - S198 2014.12

球脊髄性筋萎縮症患者の運動機能における左右差の検討 Reviewed

鈴木啓介, 勝野雅央, 坂野晴彦, 須賀徳明, 橋詰淳, 眞野智生, 荒木周, 土方靖浩, 祖父江元

臨床神経学 Vol. 54 ( Suppl. ) page： S97 - S97 2014.12

球脊髄性筋萎縮症患者の進行に対する各種薬剤の影響 Reviewed

勝野雅央, 鈴木啓介, 坂野晴彦, 須賀徳明, 橋詰淳, 荒木周, 土方靖浩, 祖父江元

臨床神経学 Vol. 54 ( Suppl. ) page： S97 - S97 2014.12

球脊髄性筋萎縮症患者の構音・嚥下障害に対する軟口蓋挙上装置の効果 Reviewed

橋詰淳, 勝野雅央, 坂野晴彦, 鈴木啓介, 須賀徳明, 眞野智生, 荒木周, 土方靖浩, 田中誠也, 山本正彦, 祖父江元

臨床神経学 Vol. 54 ( Suppl. ) page： S217 - S217 2014.12

球脊髄性筋萎縮症患者における呼吸機能の解析 Reviewed

須賀徳明, 勝野雅央, 鈴木啓介, 坂野晴彦, 橋詰淳, 荒木周, 土方靖浩, 祖父江元

臨床神経学 Vol. 54 ( Suppl. ) page： S97 - S97 2014.12

球脊髄性筋萎縮症におけるクレアチン代謝異常 Reviewed

土方靖浩, 勝野雅央, 鈴木啓介, 坂野晴彦, 須賀徳明, 橋詰淳, 荒木周, 祖父江元

臨床神経学 Vol. 54 ( Suppl. ) page： S150 - S150 2014.12

Schwann cell involvement in the peripheral neuropathy of spinocerebellar ataxia type 3. Reviewed International journal

Noriaki Suga, Masahisa Katsuno, Haruki Koike, Haruhiko Banno, Keisuke Suzuki, Atsushi Hashizume, Tomoo Mano, Masahiro Iijima, Yuichi Kawagashira, Masaaki Hirayama, Tomohiko Nakamura, Hirohisa Watanabe, Fumiaki Tanaka, Gen Sobue

Neuropathology and applied neurobiology Vol. 40 ( 5 ) page： 628 - 39 2014.8

Language：English Publishing type：Research paper (scientific journal)

AIMS: Spinocerebellar ataxia type 3 (SCA3) is an inherited spinocerebellar ataxia caused by the expansion of trinucleotide CAG repeats in the gene encoding ataxin-3. The clinical manifestations of SCA3 include peripheral neuropathy, which is an important cause of disability in a subset of patients. Although the loss of neurones in the dorsal root ganglion (DRG) has been postulated to be the cause of this neuropathy, the precise mechanism remains to be elucidated. METHODS: To clarify the clinicopathological characteristics of SCA3-associated peripheral neuropathy, we performed nerve conduction studies and histopathological analyses. Nerve conduction studies were carried out in 18 SCA3 patients. Immunohistochemical analyses of the anterior and posterior roots of the spinal cord and peripheral nerves were performed in five SCA3 patients. We also employed immunohistochemistry and immunoelectron microscopy analyses with an anti-polyglutamine antibody. RESULTS: The mean sensory nerve action potentials of the SCA3 patients were half of the normal values. The motor conduction velocities were decreased, and the distal latencies were also significantly prolonged in the nerves studied relative to the those in normal controls. Histopathological analyses detected axonal sprouting and myelin thinning in all cases. Ataxin-3 aggregates were found in the cytoplasm of Schwann cells in all of the SCA3 patients examined but not in control subjects. CONCLUSIONS: In addition to the previously reported neuronopathy, the results of the present study indicate that Schwann cells are involved in the formation of the pathogenic intracytoplasmic ataxin-3 protein aggregates in patients with SCA3-associated neuropathy.

DOI： 10.1111/nan.12055

Brugada syndrome in spinal and bulbar muscular atrophy. Reviewed International journal

Amane Araki, Masahisa Katsuno, Keisuke Suzuki, Haruhiko Banno, Noriaki Suga, Atsushi Hashizume, Tomoo Mano, Yasuhiro Hijikata, Hideaki Nakatsuji, Hirohisa Watanabe, Masahiko Yamamoto, Takeru Makiyama, Seiko Ohno, Megumi Fukuyama, Shin-Ichiro Morimoto, Minoru Horie, Gen Sobue

Neurology Vol. 82 ( 20 ) page： 1813 - 21 2014.5

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: The aim of this study was to clarify myocardial involvement and its clinical implications in subjects with spinal and bulbar muscular atrophy (SBMA), a neuromuscular disease affecting both neuronal and nonneuronal tissues. METHODS: Two independent cardiologists evaluated ECGs from a total of 144 consecutive subjects with SBMA. We performed immunohistochemical, immunoblot, and quantitative real-time PCR analyses of autopsied myocardium. RESULTS: Abnormal ECGs were detected in 70 (48.6%) of 144 subjects. The most frequent findings were ST-segment abnormalities in V1-3 (19.4%), followed by ST-segment abnormalities in V5-6 (18.1%). We detected Brugada-type ECGs in 17 of 28 subjects with ST-segment abnormalities in V1-3. Of those, one subject presented with syncope that required an implantable cardioverter defibrillator and led to eventual sudden death, and another subject also died suddenly. No subjects with Brugada-type ECGs had mutations in SCN5A, CACNA1C, or CACNB2 genes. In autopsied cases, we detected nuclear accumulation of the mutant androgen receptor protein and decreased expression levels of SCN5A in the myocardium. CONCLUSIONS: Subjects with SBMA often show Brugada-type ECG. The accumulation of the pathogenic androgen receptor may have a role in the myocardial involvement in SBMA.

DOI： 10.1212/WNL.0000000000000434

Distinct acoustic features in spinal and bulbar muscular atrophy patients with laryngospasm. Reviewed International journal Open Access

Seiya Tanaka, Haruhiko Banno, Masahisa Katsuno, Keisuke Suzuki, Noriaki Suga, Atsushi Hashizume, Tomoo Mano, Amane Araki, Hirohisa Watanabe, Hiroaki Adachi, Hiroshi Tatsumi, Masahiko Yamamoto, Gen Sobue

Journal of the neurological sciences Vol. 337 ( 1-2 ) page： 193 - 200 2014.2

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: Laryngospasm is a sudden onset of transient respiratory difficulty that is perceived as life-threatening by patients with spinal and bulbar muscular atrophy (SBMA). The purpose of the study was to analyze the voice characteristics of SBMA patients with laryngospasm using acoustic voice analysis. METHODS: Acoustic measurements were obtained from 39 consecutive Japanese patients with genetically confirmed SBMA. A comparison was made between the acoustic voice profiles of 16 patients with laryngospasm and 23 patients without laryngospasm within 6 months before the evaluation. Computerized acoustic analysis was performed for a prolonged vowel (/a:/) using the Multi-Dimensional Voice Program (MDVP). RESULTS: SBMA patients with laryngospasm had smaller fluctuations of vocal fold vibration and the turbulent noise component, indicating stronger vocal fold closure than in those without laryngospasm. Receiver operating characteristic curve analysis showed that the noise-to-harmonic ratio, which globally measures the noise components of voice, is the most useful acoustic parameter to distinguish laryngospasm (area under the curve = 0.767, p = 0.007). CONCLUSIONS: The smaller noise component in patients with laryngospasm suggests that the vocal folds of these patients are more adducted during phonation than those of the patients without laryngospasm, even in the absence of laryngospasm. Quantitative laryngeal analysis using the MDVP helps to detect laryngeal dysfunction and provides physiological insight into the pathophysiology of laryngospasm in SBMA.

DOI： 10.1016/j.jns.2013.12.010

Tongue pressure as a novel biomarker of spinal and bulbar muscular atrophy. Reviewed International journal

Tomoo Mano, Masahisa Katsuno, Haruhiko Banno, Keisuke Suzuki, Noriaki Suga, Atsushi Hashizume, Amane Araki, Hirohisa Watanabe, Seiya Tanaka, Masahiko Yamamoto, Gen Sobue

Neurology Vol. 82 ( 3 ) page： 255 - 62 2014.1

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: This study aimed to explore the reliability and validity of tongue pressure measurement as a quantitative evaluation of swallowing function in patients with spinal and bulbar muscular atrophy (SBMA). METHODS: This study enrolled 47 genetically confirmed patients with SBMA and 38 age- and sex-matched healthy controls. In both groups we measured tongue pressure using an intraoral pressure probe and assessed questionnaires that evaluated swallowing functions. We then analyzed the relationship between tongue pressure, functional scales, and the muscle weakness of other regions. RESULTS: Levels of tongue pressure were decreased in patients with SBMA within 3 years from the onset of the disease compared to healthy controls (SBMA 15.3 ± 6.4 kPa; healthy controls 37.3 ± 9.6 kPa; p < 0.001). Test-retest analysis showed a high reliability in patients with SBMA (intraclass correlation coefficient = 0.986). Tongue pressure showed a strong correlation with bulbar-related functional scales. Decrease of tongue pressure was detected in patients who reported no subjective dysphagia, and repetition of swallowing compensated for tongue weakness in such subjects. In patients with SBMA, tongue pressure more strongly correlates with the strength of pharyngeal, neck, and upper limb musculatures than with that of the lower limbs. CONCLUSION: Tongue pressure measurement is reliable and reflects swallowing function in patients with SBMA. The muscle strength of the tongue appears to decrease in SBMA before the awareness of subjective dysphagia, suggesting that tongue pressure measurement is a novel biomarker of SBMA and is applicable to early-stage detection.

DOI： 10.1212/WNL.0000000000000041