Faculty Profiles - YAMASHITA Toru

Papers - YAMASHITA Toru

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Successful treatment of anti-GAD antibody-associated autoimmune cerebellar ataxia with combined immunotherapies

Yoshio Omote, Chika Matsuoka, Ryo Sasaki, Nozomi Hishikawa, Yuko Kawahara, Emi Nomura, Namiko Matsumoto, Yuki Taira, Mami Takemoto, Ryuta Morihara, Toru Yamashita, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 9 ( 6 ) 474 - 477 2021.9

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

Anti-glutamic acid decarboxylase (GAD) antibody (Ab)-associated autoimmune cerebellar ataxia (CA) is a rare neurological disorder, and a standardized therapy has not been established. Here, we report on a 58 year-old man with type 1 diabetes mellitus, who developed progressive CA with high levels of serum and cerebrospinal fluid (CSF) anti-GAD-Ab. He was initially treated with intravenous high-dose methylprednisolone and intravenous immunoglobulin (IVIg), but his CA was gradually worsened. Additional combined immunotherapies with plasma exchange, intravenous cyclophosphamide, and rituximab finally stabilized the progressive CA and suppressed the CSF anti-GAD-Ab index. Our case suggests the effectiveness of combined immunotherapies against progressive CA and the usefulness of the CSF anti-GAD-Ab index as a therapeutic indicator.

DOI： 10.1111/ncn3.12541

Early detection of cognitive decline in mild cognitive impairment and Alzheimer's disease with a novel eye tracking test. International journal

Koh Tadokoro, Toru Yamashita, Yusuke Fukui, Emi Nomura, Yasuyuki Ohta, Setsuko Ueno, Saya Nishina, Keiichiro Tsunoda, Yosuke Wakutani, Yoshiki Takao, Takahiro Miyoshi, Yasuto Higashi, Yosuke Osakada, Ryo Sasaki, Namiko Matsumoto, Yuko Kawahara, Yoshio Omote, Mami Takemoto, Nozomi Hishikawa, Ryuta Morihara, Koji Abe

Journal of the neurological sciences 427 117529 - 117529 2021.8

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

Due to an increasing number of dementia patients, the development of a rapid and sensitive method for cognitive assessment is awaited. Here, we examined the usefulness of a novel and short (3 min) eye tracking device to evaluate the cognitive function of normal control (NC, n = 52), mild cognitive impairment (MCI, n = 52), and Alzheimer's disease (AD, n = 70) subjects. Eye tracking total score declined significantly in MCI (**p < 0.01 vs NC) and AD (**p < 0.01 vs NC, ##p < 0.01 vs MCI), and correlated well with the mini-mental state examination (MMSE) score (r = 0.57, *p < 0.05). Furthermore, the eye tracking test, especially memory and deductive reasoning tasks, effectively discriminated NC, MCI and AD. The present novel eye tracking test clearly discriminated cognitive functions among NC, MCI, and AD subjects, thereby providing an advantage for the early detection of MCI and AD in screening.

DOI： 10.1016/j.jns.2021.117529

A case of rheumatoid meningoencephalitis induced by pembrolizumab

Chika Matsuoka, Yoshio Omote, Yuko Kawahara, Ryo Sasaki, Namiko Matsumoto, Ko Tadokoro, Yuki Taira, Mami Takemoto, Ryuta Morihara, Toru Yamashita, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 9 ( 6 ) 470 - 473 2021.8

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

Immune checkpoint inhibitors occasionally cause various side effects, but the occurrence of a severe immune-related adverse event (irAE) is rare in neurology. We report on a 56-year-old woman who suffered from rheumatoid arthritis and recurrent uterine cancer. After treatment with pembrolizumab, she showed visual disturbance followed by acute fever and consciousness disturbance with high-intensity lesions around the midbrain aqueduct and bilateral caudate heads on FLAIR images of a brain MRI. Her symptoms improved after steroid therapy. However, symptoms relapsed leading to an elevation of the anti-CCP antibody index. Pembrolizumab-induced rheumatoid meningoencephalitis was suspected, so additional steroid therapy was provided. This improved her symptoms, turning the anti-CCP antibody index negative. The present case is the first case of rheumatoid meningoencephalitis induced by pembrolizumab. The combination of MRI findings and elevated anti-CCP index seems useful for diagnosing rheumatoid meningoencephalitis.

DOI： 10.1111/ncn3.12540

A Unique Case of Encephalopathy with an Elevated IgG-4 and Extremely High Interleukin-6 Level and Delayed Myelodysplastic Syndrome.

Namiko Matsumoto, Nozomi Hishikawa, Ken Ikegami, Kota Sato, Yoshio Omote, Mami Takemoto, Toru Yamashita, Kohei Taniguchi, Koji Abe

Internal medicine (Tokyo, Japan) 60 ( 13 ) 2125 - 2128 2021.7

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

We herein report a 75-year-old man who developed disturbed consciousness with polynuclear cell dominant pleocytosis and low glucose and extremely high interleukin (IL)-6 levels in his cerebrospinal fluid. The biopsy specimen from his right supraclavicular lymph node showed the infiltration of inflammatory cells positive for IgG, IgG4 and IL-6. Prednisolone and azathioprine administered under suspicion of IgG4-related disease (IgG4-RD) or multicentric Castleman's disease (MCD) successfully remitted the symptoms. However, he developed myelodysplastic syndrome (MDS) and died 18 months later. The extremely high IL-6 may have been related to the rare neurological manifestations and development of MDS in the present case.

DOI： 10.2169/internalmedicine.6098-20

Switching the Proteolytic System from the Ubiquitin-Proteasome System to Autophagy in the Spinal Cord of an Amyotrophic Lateral Sclerosis Mouse Model. International journal

Koh Tadokoro, Toru Yamashita, Jingwei Shang, Yasuyuki Ohta, Emi Nomura, Ryuta Morihara, Yoshio Omote, Mami Takemoto, Koji Abe

Neuroscience 466 47 - 57 2021.7

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

The degradation of damaged proteins takes place via two major proteolytic pathways: the ubiquitin-proteasome system (UPS) and autophagy. However, since it is unclear how these two proteolytic pathways contribute to the pathogenesis of amyotrophic lateral sclerosis (ALS), we investigated the switching mechanism from UPS to autophagy by pharmacologically modifying these pathways by treating the spinal cords of female ALS mouse model bearing G93A human SOD1 (G93A mice) with MG132 or 3-methyladenine (3MA). G93A mice exhibited a progressive increase in the amount of ubiquitin and p62 aggregates, BAG3 expression, and LC3-II/LC3-I ratio in both astroglia and motor neurons. Treatment with MG132 or 3MA significantly increased the clinical hanging wire score and exacerbated α-motor neuron loss at 18 weeks in G93A mice, and increased the amount of ubiquitin, p62 aggregates, and BAG3 expression. This study's results demonstrate that the molecular switch from UPS to autophagy occurred not only in motor neurons but also in astroglia at the end stage (18 weeks) when the autophagic flux was impaired in G93A mice. This finding suggests that the defense system was disrupted against aggregate-prone protein production in ALS.

DOI： 10.1016/j.neuroscience.2021.04.034

The first case of chronic inflammatory demyelinating polyneuropathy after transsexualism and continuous testosterone administration

Yuki Taira, Yoshio Omote, Yuko Kawahara, Emi Nomura, Ryo Sasaki, Namiko Matsumoto, Chika Matsuoka, Mami Takemoto, Ryuta Morihara, Nozomi Hishikawa, Toru Yamashita, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 9 ( 4 ) 346 - 348 2021.7

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

We report on a 35-year-old man who had gender dysphoria following unilateral ovariectomy and then received continuous testosterone injection for nine years, inducing chronic inflammatory demyelinating polyneuropathy (CIDP). He developed recurrent muscle weakness and numbness in the extremities and displayed demyelinating neuropathy, detected by nerve conduction studies and a sural nerve biopsy. Repeated intravenous immunoglobulin (IVIg) therapy and the administration of oral prednisolone improved symptoms and inhibited their recurrence. A relatively high level of serum testosterone as a genetic female might have caused the neurotoxicity of the peripheral nerve, leading to CIDP.

DOI： 10.1111/ncn3.12514

Author Correction: Therapeutic benefit of Muse cells in a mouse model of amyotrophic lateral sclerosis. International journal

Toru Yamashita, Yoshihiro Kushida, Shohei Wakao, Koh Tadokoro, Emi Nomura, Yoshio Omote, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Mari Dezawa, Koji Abe

Scientific reports 11 ( 1 ) 12828 - 12828 2021.6

Hypoxic stress visualized in the cervical spinal cord of ALS patients. International journal

Toru Yamashita, Tetsuhiro Hatakeyama, Kota Sato, Yusuke Fukui, Nozomi Hishikawa, Mami Takemoto, Yasuyuki Ohta, Yoshihiro Nishiyama, Nobuyuki Kawai, Takashi Tamiya, Koji Abe

Neurological research 43 ( 6 ) 429 - 433 2021.6

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

Objective: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal motor neuron disease. Hypoxic stress is suspected as the pathogenesis of ALS, however, no positron emission tomography (PET) study for hypoxic stress has been conducted in the spinal cord of ALS patients.Methods: In the present study, we examined cervical spinal hypoxic stress of nineALS patients with upper extremity (U/E) atrophy by18F-fluoromisonidazole (FMISO) PET.Results: On the ipsilateral side of C1 and C5 levels, 18F-FMISO uptake increased significantly compared with the contralateral side (*p < 0.05) and the control subject (**p < 0.01). In addition, a strong correlation was found between 18F-FMISO uptake of the C5 level and the rate of progression of the ALS FRS-R score (R = 0.781, *p = 0.013).Conclusion: These results indicate that hypoxic stress increased in the spinal cord of ALS patients with a close link to ALS progression. Both hypoxic stress and a compromised response to hypoxia, which may lead to subsequent motor neuron death, could be a potential therapeutic target for ALS.

DOI： 10.1080/01616412.2020.1866383

Protective effects of edaravone on white matter pathology in a novel mouse model of Alzheimer's disease with chronic cerebral hypoperfusion. International journal

Tian Feng, Toru Yamashita, Ryo Sasaki, Koh Tadokoro, Namiko Matsumoto, Nozomi Hishikawa, Koji Abe

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 41 ( 6 ) 1437 - 1448 2021.6

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

White matter lesions (WMLs) caused by cerebral chronic hypoperfusion (CCH) may contribute to the pathophysiology of Alzheimer's disease (AD). However, the underlying mechanisms and therapeutic approaches have yet to be totally identified. In the present study, we investigated a potential therapeutic effect of the free radical scavenger edaravone (EDA) on WMLs in our previously reported novel mouse model of AD (APP23) plus CCH with motor and cognitive deficits. Relative to AD with CCH mice at 12 months (M) of age, EDA strongly improved CCH-induced WMLs in the corpus callosum of APP23 mice at 12 M by improving the disruption of white matter integrity, enhancing the proliferation of oligodendrocyte progenitor cells, attenuating endothelium/astrocyte unit dysfunction, and reducing neuroinflammation and oxidative stress. The present study demonstrates that the long-term administration of EDA may provide a promising therapeutic approach for WMLs in AD plus CCH disease with cognitive deficits.

DOI： 10.1177/0271678X20968927

Neuroprotective effect of CuATSM in mice stroke model by ameliorating oxidative stress. Reviewed International journal

Xiaowen Shi, Yasuyuki Ohta, Yumiko Nakano, Xia Liu, Koh Tadokoro, Tian Feng, Emi Nomura, Keiichiro Tsunoda, Ryo Sasaki, Namiko Matsumoto, Yosuke Osakada, Yuting Bian, Zhihong Bian, Yoshio Omote, Mami Takemoto, Nozomi Hishikawa, Toru Yamashita, Koji Abe

Neuroscience research 166 55 - 61 2021.5

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

Cu-diacetyl-bis (N4-methylthiosemicarbazone) (CuATSM) has both anti-oxidative and anti-inflammatory activities, but its therapeutic efficacy for oxidative stress has not been thoroughly investigated in acute ischemic stroke. Here, the present study was designed to assess the efficacies of CuATSM in acute ischemic stroke by comparing with the standard neuroprotective reagent edaravone. Mice were subjected to transient middle cerebral occlusion (tMCAO) for 60 min, and then intravenously administrated with CuATSM (1.5 mg/kg) or edaravone (3 mg/kg) just after the reperfusion, and examined at 1 and 3 d. Compared with the vehicle group, CuATSM treatment decreased infarct volumes and oxidative stress at 3d after tMCAO, which was further enhanced by combined CuATSM + edaravone treatment as compared with single CuATSM group, but not improve neurobehaviors. The present study demonstrated that CuATSM showed strong antioxidative and neuroprotective effects in acute ischemic stroke, which was enhanced by the combination with edaravone.

DOI： 10.1016/j.neures.2020.05.009

Positive baseline behavioral and psychological symptoms of dementia predict a subsequent cognitive impairment in cognitively normal population

Keiichiro Tsunoda, Toru Yamashita, Yosuke Osakada, Ryo Sasaki, Koh Tadokoro, Namiko Matsumoto, Emi Nomura, Noriko Hatanaka, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 9 ( 3 ) 218 - 222 2021.5

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

Background: Because behavioral and psychological symptoms of dementia (BPSD) are sometimes prodromal symptoms of dementia, it is important to investigate the relationship between BPSD and subsequent cognitive decline.Methods: We examined the cognitive and affective functions of 76 cognitively normal subjects at initial assessment (baseline) and 1-year follow-up. Cognitive function was assessed using clinical dementia rating (CDR) and Mini-Mental State Examination (MMSE), and affective function was assessed using Abe's BPSD score (ABS) and mild behavioral impairment (MBI).Results: Although there was no change in MMSE, ABS, or MBI after 1 year, the mean CDR score of 0 at baseline increased to 0.1 +/- 0.2 at 1-year follow-up (**P < 0.01 vs baseline). No significant change in MMSE was found in both baseline ABS and MBI positive- or negative-groups. In contrast, baseline MBI-dependent CDR change showed a 13.2% of worsening in MBI-negative subjects and a 62.5% of MBI-positive subjects (dagger dagger P < 0.01), but ABS not.Conclusion: The present data indicate that positive baseline BPSD with MBI was closely related to a subsequent CDR exacerbation. Examining BPSD may be useful for screening cognitively normal population for subsequent dementia development in local communities.

DOI： 10.1111/ncn3.12492

Non-Tumorigenic Pluripotent Reparative Muse Cells Provide a New Therapeutic Approach for Neurologic Diseases. International journal

Toru Yamashita, Yoshihiro Kushida, Koji Abe, Mari Dezawa

Cells 10 ( 4 ) 2021.4

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

Muse cells are non-tumorigenic endogenous reparative pluripotent cells with high therapeutic potential. They are identified as cells positive for the pluripotent surface marker SSEA-3 in the bone marrow, peripheral blood, and connective tissue. Muse cells also express other pluripotent stem cell markers, are able to differentiate into cells representative of all three germ layers, self-renew from a single cell, and are stress tolerant. They express receptors for sphingosine-1-phosphate (S1P), which is actively produced by damaged cells, allowing circulating cells to selectively home to damaged tissue. Muse cells spontaneously differentiate on-site into multiple tissue-constituent cells with few errors and replace damaged/apoptotic cells with functional cells, thereby contributing to tissue repair. Intravenous injection of exogenous Muse cells to increase the number of circulating Muse cells enhances their reparative activity. Muse cells also have a specific immunomodulatory system, represented by HLA-G expression, allowing them to be directly administered without HLA-matching or immunosuppressant treatment. Owing to these unique characteristics, clinical trials using intravenously administered donor-Muse cells have been conducted for myocardial infarction, stroke, epidermolysis bullosa, spinal cord injury, perinatal hypoxic ischemic encephalopathy, and amyotrophic lateral sclerosis. Muse cells have the potential to break through the limitations of current cell therapies for neurologic diseases, including amyotrophic lateral sclerosis. Muse cells provide a new therapeutic strategy that requires no HLA-matching or immunosuppressant treatment for administering donor-derived cells, no gene introduction or differentiation induction for cell preparation, and no surgery for delivering the cells to patients.

DOI： 10.3390/cells10040961

Longitudinal changes in antipsychotic dose in patients treated with long-acting injectable second-generation antipsychotics. International journal

Nozomi Nakajima, Nao Mizoe, Fuminari Misawa, Toru Yamashita, Ryuhei So, Kohei Kitagawa, Kenichi Tanimoto, Yoshiki Kishi, Yasuo Fujii, Hiroyoshi Takeuchi

International clinical psychopharmacology 36 ( 2 ) 84 - 88 2021.3

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

Only a few studies have investigated changes in the dose of long-acting injectable second-generation antipsychotics (LAI-SGAs) over the long term in the maintenance treatment of schizophrenia. In this retrospective cohort study, we examined longitudinal changes in antipsychotic dose over a 3-year period in patients with schizophrenia who had been taking LAI-SGAs for at least 1 year. We compared the total daily chlorpromazine equivalent dose of antipsychotics at 12, 24 and 36 months with the baseline dose at 3 months after initiation of LAI-SGAs. We also performed multiple regression analysis to explore factors associated with change in total daily dose 12 months after treatment initiation. A total of 154 patients fulfilled the inclusion criteria. There was no significant difference in total daily antipsychotic dose between 3 months and 12, 24 or 36 months after treatment initiation. Total daily dose was increased in 43 (27.9%), 31 (34.8%) and 22 patients (36.7%) at 12, 24 and 36 months, respectively. Age and total antipsychotic dose at 3 months were significantly negatively associated with change in total daily dose. Antipsychotic dose was basically unchanged during long-term treatment in patients treated with LAI-SGAs in the maintenance phase, although there was an increase in some patients.

DOI： 10.1097/YIC.0000000000000347

A new telestroke network system in northern area of Okayama prefecture

Ryo Sasaki, Toru Yamashita, Yoshio Omote, Mami Takemoto, Nozomi Hishikawa, Taijun Yunoki, Kazuki Kobayashi, Takashi Sawata, Yuki Sato, Junichi Kubota, Masayuki Mizobuchi, Takashi Hayashi, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 9 ( 2 ) 166 - 170 2021.3

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

Background: Telestroke network can provide rapid access to specialized treatment and improves on-site management of acute stroke patients through the "hub-and-spoke" model. In the northern part of Okayama Prefecture, there has been a regional gap of stroke care due to the shortage of stroke specialists and facilities. In addition, due to the novel coronavirus disease 2019 (COVID-19), it is required to reduce the unnecessary contact with stroke patients from other hospitals.Aim: We organized a novel cost-free telestroke network with an image and video sharing for neurological diseases in the northern part of Okayama Prefecture to improve the stroke management in the area.Method: We prepared the tablet device on which Skype(R) application was installed for each hospital and recruited the patients who visited or hospitalized in the spoke hospitals and were suspected to have some neurological diseases from April 2019 to May 2020. The patient's clinical data were recorded and analyzed.Results: During the study period, 5 patients were recruited including the cases with the initial diagnosis of stroke or brain tumor. Among them, 2 cases were transferred to the hub hospital, 2 cases were transferred to other hospitals, and 1 case was treated on site under specialist's advice.Conclusion: The new telestroke network system may be beneficial for acute stroke management and reducing the unnecessary patient's transfer in the rural area, especially under coexistence with COVID-19.

DOI： 10.1111/ncn3.12475

4-Hydroxyl-2-Nonenal Localized Expression Pattern in Retrieved Clots is Associated with Large Artery Atherosclerosis in Stroke Patients. International journal

Yosuke Osakada, Toru Yamashita, Ryuta Morihara, Namiko Matsumoto, Ryo Sasaki, Koh Tadokoro, Emi Nomura, Yuko Kawahara, Yoshio Omote, Nozomi Hishikawa, Mami Takemoto, Yasuyuki Ohta, Yasuki Suruga, Takayuki Nagase, Yuji Takasugi, Satoshi Inoue, Kyoichi Watanabe, Kentaro Deguchi, Koji Tokunaga, Susumu Sasada, Kazuki Kobayashi, Ryosuke Maeoka, Kenji Fukutome, Kenkichi Takahashi, Hiroyuki Ohnishi, Yoshihiro Kuga, Hideyuki Ohnishi, Koji Abe

Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 30 ( 3 ) 105583 - 105583 2021.3

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

OBJECTIVES: The relationship between stroke etiology and clot pathology remains controversial. MATERIALS AND METHODS: We performed histological analysis of clots retrieved from 52 acute ischemic stroke patients using hematoxylin and eosin staining and immunohistochemistry (CD42b and oxidative/hypoxic stress markers). The correlations between clot composition and the stroke etiological group (i.e., cardioembolic, cryptogenic, or large artery atherosclerosis) were assessed. RESULTS: Of the 52 clots analyzed, there were no significant differences in histopathologic composition (e.g., white blood cells, red blood cells, fibrin, and platelets) between the 3 etiological groups (P = .92). By contrast, all large artery atherosclerosis clots showed a localized pattern with the oxidative stress marker 4-hydroxyl-2-nonenal (P < .01). From all 52 clots, 4-hydroxyl-2-nonenal expression patterns were localized in 28.8% of clots, diffuse in 57.7% of clots, and no signal in 13.5% of clots. CONCLUSIONS: A localized pattern of 4-hydroxyl-2-nonenal staining may be a novel and effective marker for large artery atherosclerosis (sensitivity 100%, specificity 82%).

DOI： 10.1016/j.jstrokecerebrovasdis.2020.105583

Effect of edaravone on pregnant mice and their developing fetuses subjected to placental ischemia. International journal

Marwa Atallah, Toru Yamashita, Koji Abe

Reproductive biology and endocrinology : RB&E 19 ( 1 ) 19 - 19 2021.2

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

Growing evidence indicates that reduced uterine perfusion pressure (RUPP) triggers the cascade of events leading to preeclampsia. Edaravone is a powerful free radical scavenger used for the treatment of ischemia/reperfusion diseases due to its anti-oxidative stress and anti-inflammatory properties. Here we investigate the effect of edaravone (3 mg/kg) on different maternal and fetal outcomes of RUPP-induced placental ischemia mice model. RUPP surgery was performed on gestation day (GD) 13 followed by edaravone injection from GD14 to GD18, sacrifice day. The results showed that edaravone injection significantly decreased the maternal blood pressure (113.2 ± 2.3 mmHg) compared with RUPP group (131.5 ± 1.9 mmHg). Edaravone increased fetal survival rate (75.4%) compared with RUPP group (54.4%), increased fetal length, weights, and feto-placental ratio (7.2 and 5.7 for RUPP and RUPP-Edaravone groups, respectively) compared with RUPP group. In addition, RUPP resulted in many fetal morphological abnormalities as well as severe delayed ossification, however edaravone decreased the morphological abnormalities and increased the ossification of the fetal endoskeleton. Edaravone improved the histopathological structure of the maternal kidney and heart as well as decreased the elevated blood urea and creatinine levels (31.5 ± 0.15 mg/dl (RUPP), 25.6 ± 0.1 mg/dl (RUPP+edaravone) for urea and 5.4 ± 0.1 mg/dl (RUPP), 3.5 ± 0.1 mg/dl (RUPP+edaravone) for creatinine) and decreased cleaved caspase-3 expression in the maternal kidney. In conclusion, this study demonstrated that our RUPP mice model recapitulated preeclampsia symptoms and edaravone injection ameliorated most of these abnormalities suggesting its effectiveness and potential application in preeclampsia treatment regimes.

DOI： 10.1186/s12958-021-00707-2

The Oldest Japanese Case of Combined Central and Peripheral Demyelination, which Developed Nine Years After the First Instance of Optic Neuritis.

Emi Nomura, Yuko Kawahara, Yoshio Omote, Koh Tadokoro, Mami Takemoto, Nozomi Hishikawa, Toru Yamashita, Hidenori Ogata, Koji Abe

Internal medicine (Tokyo, Japan) 60 ( 2 ) 305 - 308 2021.1

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

Combined central and peripheral demyelination (CCPD) causes demyelination in both the central and peripheral nervous systems. Anti-neurofascin 155 antibody plays an important pathogenic role in CCPD, but evidence concerning an association between this antibody and CCPD remains inconclusive. Although there have been no reports of precedent optic neuritis developing into CCPD, we herein report a Japanese man in whom optic neuritis recurred four times over nine years and who developed CCPD without positive anti-neurofascin 155 antibody. This case suggests the possibility of developing CCPD after optic nerve neuritis and the existence of an unknown antibody that induces CCPD.

DOI： 10.2169/internalmedicine.5536-20

A case of Kii amyotrophic lateral sclerosis/parkinsonism dementia complex presenting as progressive parkinsonism with corresponding tau imaging

Yasuyuki Ohta, Hitoshi Shimada, Ken Ikegami, Keiichiro Tsunoda, Nozomi Hishikawa, Toru Yamashita, Mami Takemoto, Yoshio Omote, Kenji Tagai, Kiwamu Matsuoka, Makoto Higuchi, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 9 ( 1 ) 124 - 126 2021.1

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

Amyotrophic lateral sclerosis/parkinsonism dementia complex (ALS/PDC), frequently observed in the Kii peninsula of Japan, is pathologically characterized by widespread tau pathology in the cerebrum and brainstem. Here, we report a case of Kii ALS/PDC predominantly presenting progressive parkinsonism. Tau positron emission tomography (PET) imaging with F-18-PM-PBB3 suggested tau deposition in the substantia nigra of the midbrain and subcortical areas, but not in the cerebral cortex, which was similar to progressive supranuclear palsy (PSP), suggesting that parkinsonism-predominant type of Kii ALS/PDC may have a similar area of tau deposition to PSP.

DOI： 10.1111/ncn3.12463

Recurrent severe and long-lasting cerebellar ataxia attacks in adult-onset neuronal intranuclear inclusion disease

Yosuke Osakada, Kentaro Deguchi, Shoko Deguchi, Fumiyo Higaki, Wakako Oda, Mari Yoshida, Yasuyuki Ohta, Toru Yamashita, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 9 ( 1 ) 107 - 110 2021.1

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

Neuronal intranuclear inclusion disease (NIID) is a progressive neurodegenerative disease that is characterized by eosinophilic hyaline intranuclear inclusions. NIID presents highly variable clinical manifestations such as dementia, ataxia, convulsion, neuropathy, and autonomic dysfunction. A 60-year-old woman developed recurrent severe cerebellar ataxia (SARA score: 30/40 points). She was diagnosed with adult-onset NIID by a characteristic brain diffusion-weighed imaging hyperintensity lesion in subcortical white matter and intranuclear inclusion bodies in a skin biopsy. Her ataxia was more severe and lasted longer (additional 19 days) than a previous case, although she showed remarkable improvement.

DOI： 10.1111/ncn3.12454

A case of autoimmune GFAP astrocytopathy with profound weight loss and increased uptake in the spinal cord on F-18-FDG PET

Yosuke Osakada, Yoshio Omote, Ken Ikegami, Koh Tadokoro, Kota Sato, Nozomi Hishikawa, Mami Takemoto, Yasuyuki Ohta, Toru Yamashita, Akio Kimura, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 9 ( 1 ) 95 - 97 2021.1

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

A 76-year-old man presented with subacute onset of progressive cognitive impairment, anorexia, tremor, ataxic gait, and urinary dysfunction. He had lost 17 kg in 9 months before his admission (due to persistent anorexia). A brain MRI showed a typical radial pattern of periventricular gadolinium enhancement and longitudinally extensive hyperintensity from cervical to lumbar spinal cord. F-18-FDG PET newly revealed an increased uptake of the tracer in the cervical and lower thoracic cords. After an intravenous methylprednisolone (1000 mg/d for 3 days) followed by oral prednisolone 40 mg/d, his clinical symptoms and abnormal MRI lesions improved. Anti-GFAP antibodies were subsequently identified in CSF obtained on admission, confirming the diagnosis of autoimmune GFAP astrocytopathy.

DOI： 10.1111/ncn3.12441

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