Pe-07-10
Theclinicalandimmunologicalfeaturesof NMOpatientswithonsetover80yearsold○AyakaOno1,EtsujiSaji1,AkihiroNakajima1,TakahiroWakasugi1, FumihiroYanagimura1,3,KaoriYanagawa1,MasatoyoNishizawa4, OsamuOnodera1,IzumiKawachi1,2
1 Department of Neurology, Brain Research Institute, Niigata University, Japan, 2 Comprehensive Medical Education Center, Niigata University School of Medicine, 3 Department of Neurology, NHO Niigata Hospital, 4 Niigata University of Health and Welfare
[Objective] Neuromyelitis optica spectrum disorders （NMOSD） are autoimmune inflammatory CNS diseases. Most of NMOSD patients have the aquaporin 4 （AQP4）
autoantibodies. The study aimed to identify clinical and immunological features of very late-onset NMOSD patients. [Methods] This study retrospectively included 73 Japanese NMOSD patients, met the international consensus 2015 diagnostic criteria of NMOSD.
We identified three NMOSD patients as having onset over 80 years old. [Results] All three patients with onset over 80 years old NMOSD had the seropositivity of AQP4 antibodies by using cell-based assay. Case 1; An 80-year-old man had developed hiccup and tetraplegia with the medulla oblongata and cervical spinal cord lesions. Although prednisolone treatment slightly improved muscle weakness, he had been bedridden.
Preserved serum found to be positive of AQP4 antibody. Case 2; An 86-year-old woman noticed of left blurred vision. Her left visual acuity was no light perception. The antibody for AQP4 （ELISA） was negative. Platelia Aspergillus antigen was positive. Steroid pulse therapy and voriconazole did not improve visual acuity. Case 3; An 88-year-old woman developed visual impairment in the right eye. Three weeks later, she presented with temporal hemianopia in the left eye. AQP4 antibody and Platelia Aspergillus antigen were positive. Steroid pulse therapy improved visual acuity from 0.06 to 0.4 in the left eye, but the right visual acuity （hand motion） did not change. [Conclusions] Onset age of NMOSD patients could be over 80 years old in contrast to multiple sclerosis.
Pe-08-1
TheroleofactivatedvitaminDforthebarrier functionoftheendomysialendothelium○YasuteruSano,ToshihikoMaeda,FumitakaShimizu, YukioTakeshita,MasayaHonda,TakashiKanda
Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine, Japan
Purpose: Dermatomyositis （DM） is an immune-mediated disorder that most prominently involves muscle and skin. The loss of tight junction （TJ） of some remaining microvasculature is a hallmark of DM. Recently, low serum level of vitamin D has been reported to be a risk factor for developing inflammatory myopathy including DM. In addition, it is reported that activated vitamin D strengthened the barrier function of endothelium constituting the blood-brain barrier. In this study, we investigated the effect of activated vitamin D to the barrier properties of the endomysial endothelium, using a human skeletal muscle microvascular endothelial cell line （TSM15）. Method: The mRNA levels of tight junction molecules as well as cell adhesion molecules were examined after incubation with conditioned medium （CM） with or without 1α, 25（OH）2D3 . The transendothelial electrical resistance （TEER） across the layer of TSM15 in response to treatment with 1α, 25（OH）2D3 was also measured. Results and discussion: The addition of 1α, 25（OH）2D3 to TSM15 increased the mRNA levels of occludin and ZO1, and reduced those of VCAM-1 and ICAM-1. 1α, 25
（OH）2D3 also elevated the TEER of TSM15. These results indicate that activated vitamin D strengthen the barrier function of endomysial endothelium through the up-regulation of occludin and ZO-1, and prevent the entry of inflammatory lymphocytes into the endomysium through the down-regulation of cell adhesion molecules. Conclusion: The activated vitamin D might ameliorate the pathophysiology of DM via restoring the fragile barrier of endomysial endothelium.
Pe-08-2
Histologicalinvestigationofnecroptosisinanti-SRPmyopathy○MasatoshiOmoto,ToshihikoMaeda,TakashiKanda Neurology and Clinical Neuroscience, yamaguchi University, Japan Background and Objective]Necroptosis has been linked to many pathological conditions and afflictions, such as ischemia, neurodegeneration, viral infections, and inflammation. RIPK1, RIPK3, and MLKL are central regulators of this pathway. Histopathological findings of anti-SRP myopathy biopsy specimens were characterized by numerous necrotic and regenerating fibers, deposits of the membrane attack complex, and lack of conspicuous lymphocytic invasion.
Although it has been hypothesized that the complement-dependent antibody-mediated mechanism underlies anti-SRP myopathy （J Neuroimmnol 2013, Neurology 2018）, the underlying molecular immune mechanisms remain unknown. A recent in vitro study reported that necroptosis involves pro-death regulators in complement-mediated cell death （Front Immunol 2018）. This study aimed to examine the involvement of necroptosis in anti-SRP myopathy using biopsied muscle specimens.[Materials and Methods] RIPK1, RIPK3, and MLKL expression was immunohistochemically investigated in biopsied muscle specimens （five control, seven anti-SRP myopathy, and five dermatomyositis）.
[Results]RIPK1, RIPK3, and MLKL expression was observed in numerous muscle fibers of all anti-SRP myopathy biopsy specimens, but it was less conspicuous in the dermatomyositis biopsy specimen. Furthermore, RIPK1, RIPK3, and MLKL were not expressed in the muscle fibers of the control specimen.[Conclusion] Necroptosis was involved in muscle fiber collapse in anti-SRP myopathy, and may act as a regulator in complement-mediated muscle fiber death in anti-SRP myopathy.
Pe-08-3
ElectricalexcitabilityofhumaniPSCs-derived musclecells○TomoyaKubota1,KeiFujiwara2,RisaYamamoto1,ItsukiMori1, TasukuOhso1,YukoSuzuki3,MasayoshiKamon4,ToshiyukiAraki4, HidetoshiSakurai2,MasanoriTakahashi1
1 Lab of Clinical neurophysiology, Osaka University Graduate School of Medicine, Japan, 2 Center for iPS Cell Research and Application （CiRA）, Kyoto University, 3 Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4 Department of Peripheral Nervous System Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry
[Objective]Skeletal muscle is an organ which has both an electrical excitability and a mechanical durability. The electrical excitability of the mature skeletal muscle relies on a generator of an action potential, a voltage-gated Na channel （Nav1.4） encoded by SCN4A gene. Interestingly, the cardiac Nav1.5 encoded by SCN5A also expresses in immature skeletal muscle. During the myogenesis, Nav1.4 is upregulated by maturation instead of Nav1.5. Recently, several human induced pluripotent stem cells （iPSCs）-based models for skeletal muscle diseases have been proposed, but the electrical excitability has been obscure. The objective in this study is to analyze the electrical excitability of iPSCs-derived muscle cells. [Methods] We obtained iPSCs-derived muscle cells induced from muscle stem cells isolated from differentiated iPSCs. Using the RNA extracted, the ion channel gene expression profile was analyzed by qPCR. Whole cell patch clamp experiments were performed and evaluated the voltage dependence of ionic currents recorded.
[Results] SCN4A gene expression was upregulated in a differentiation dependent manner whereas SCN5A gene was not. Transient inward currents elicited by membrane depolarization were recorded and the voltage-dependence were indistinguishable from that of Na+ currents recorded from HEK293T cells expressing Nav1.4 channels. Moreover, the inward currents showed sensitivity to tetrodotoxin, indicating that Nav1.4 expresses dominantly. [Conclusions]Our iPSCs-derived muscle cells may harbor an electrical excitability comparable with mature skeletal muscle cells.
Pe-08-4
TheeffectofIgGfrominflammatorymyopathypatients onhumanmusclemicrovascularendothelialcell○MasayaHonda,FumitakaShimizu,YukioTakeshita, ToshihikoMaeda,YasuteruSano,TakashiKanda
Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine, Japan
Background: Idiopathic inflammatory myopathies （IIM） are heterogeneous disorders. In dermatomyositis, pathological findings included perifascicular atrophy, infiltration of lymphocytes and deposition of complement around the endomysial capillaries, suggesting the involvement of vasculature in its pathogenesis. However, there is no direct evidence that circulating autoantibodies have some roles on the muscle vasculature in the development of IIM. To address this issue, we recently established a novel human muscle microvascular endothelial cell （HMMEC） line. Objective: The purpose of this study is to clarify the effect of IgG from IIM patients on the HMMEC. Methods:
We purified serum IgG from 42 sera with IIM patients, 21 non-inflammatory disease controls and 12 healthy controls. The amount of IgG-binding HMMECs and nuclear NF-κB p65 positive HMMECs was analyzed using the high-content imaging system after exposure to IgG. Results: 13 of 42 IIM patients group bound to HMMECs. On the other hand, no control IgG bound to HMMECs.
Two IgGs from the IIM patients significantly induced nuclear translocation of NF-κB p65, whereas no IgGs from disease or healthy controls were induced.
Conclusion: We identified several IgGs from IIM patients that can bind to HMMECs and two IgGs from the IIM patients which induced endothelial cell activation. There results showed that autoantibodies against endothelial cells in the endomysial capillaries may has pathogenic effects on microvasculature in IIM. Further analysis is ongoing to clarify the pathomechanism of these antibodies in IIM.
Pe-08-5
Adeficitofshortisoformofbraindystrophinimpairs excitatory-inhibitorybalanceintheamygdala○YasumasaHashimoto1,2,HiroshiKuniishi3,4,MasahiroFukaya5, HiroyukiSakagami5,KeijiWada3,Shin'ichiTakeda1, MasayukiSekiguchi3,YoshitsuguAoki1
1 Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry （NCNP）, Japan, 2 Department of Neurology, Kansai medical university, Japan, 3 Department of Degenerative Neurological Diseases, National Institute of Neuroscience, NCNP, 4 Department of Neuropsychopharmacology, National Institute of Mental Health, NCNP, 5 Department of Anatomy, Kitasato University School of Medicine
Purpose: Duchenne muscular dystrophy （DMD） patients with dystrophin deficiency show psychiatric symptoms such as anxiety and autism spectrum disorders （ASD）. We have previously reported that a deficit of Dp427c, a brain full-length dystrophin, isoforms impairs specific amygdala GABAergic transmission and enhances fear response in mice. Interestingly, the absence of Dp140, a brain dystrophin short isoform, is associated with a high prevalence of ASD in DMD. We aim to clarify the molecular function of brain Dp140 in a hot spot of deletion mutations, after treatment of skeletal muscle using antisense oligonucleotide.
Method: The basolateral amygdala （BLA） tissues were collected from 8-week-old C57BL/6 （WT）, mdx23 lacking Dp427c and mdx52 mice lacking both Dp140 and Dp427c. We performed molecular biological and electrophysiological analyses to investigate GABAergic and glutamatergic transmissions. Result: Dp140 expression in the BLA was confirmed by western blotting in mdx23 but not in mdx52 mice. The numbers of GABAA receptors and the expression level of VGLUTs in the BLA by immunohistochemistry are reduced in mdx52 compared to mdx23. Significantly the impaired E/I ratio was only seen in the BLA pyramidal neurons of mdx52. Sniffing time by a social behavior test in mdx52 was significantly prolonged compared with WT and mdx23. Conclusion: We assume that a deficit of Dp140 causes the impairment of E/I balance in the murine amygdala. Moreover, we are investigating whether electrophysiological and behavioral abnormalities normalize when Dp140 is induced by exon skipping therapy.
一 般 演 題
ポ ス タ ー （ 英 語 ）
Pe-07-4
ShortenedtelomereG-taillengthin10patients withadverseeffectsafterHPVvaccination○ToshiakiHirai1,YoshiyukiKuroiwa1,2,YukieNishiyama3, HidetoshiTahara3,YasuhisaBaba1,IkuroNakamura2, KusukiNishioka4,5
1 Department of Neurology and Stroke Center, Mizonokuchi Hospital, Teikyo University School of Medicine, Kawasaki, Japan, 2 Medical Office, Ministry of Japan, Tokyo, Japan, 3 Department of Cellular and Molecular Biology, Graduate School of Biomedical Sciences, Hiroshima University, 4 Japan Medical Research Foundation, Tokyo, Japan, 5 National Graduate Institute for Policy Studies, Tokyo, Japan
[Objective] Human papilloma virus vaccination （HPVV） associated neuro-immunopathic syndrome
（HANS proposed by Nishioka） presents clinical symptoms of hypothalamic disorders （hypothalamic syndrome）, increased auto-antibodies against the autonomic nervous system, low values of coefficient of variation R-R interval （CV-RR）, decreased cerebral blood flow at the anterior cingulate gyrus, and loss of circadian hormonal rhythm. Our previous study on natural history of HANS showed that severity scores measured by mRS （modified Rankin Scale） extend to the maximum at 4 years after 1st HPVV. Such a progressive period of HANS lasting 4 years does not suggest ADEM or usual autoimmune limbic encephalopathy but epigenetic dysregulation of hypothalamic homeostasis. Therefore we decided to investigate telomeres in HANS as epigenetic bio-markers.
[Methods] We enrolled 10 HANS patients （18-23 years old females）, and measured their mRS, CV-RR, total telomere length （TL）, %TL （TL/ TL in normal subjects）, telomere G-tail length （GL）,
%GL （GL/ GL in normal subjects）, and the degree of genetic fatigue （GF） calculated as 100 times of GL/TL using a hybridization protection assay （Tahara H, Nature Methods 2005）. [Results] We found normal %TL （104±12.6）, decreased %GL （50.9±7.6）, and decreased GF （7.2±1.4） in any of 10 HANS patients. We noted negative correlations between CV-RR and GF （R2=0.42）, and between mRS and GF （R2=0.40）. [Conclusions] We found for the first time remarkable shortening of telomere G-tail length in HANS, suggesting chromosomal instability of epigenetic origin caused by HPVV.
Pe-07-7
Cerebrallesionsandvolumeinmultiple sclerosisandneuromyelitisoptica○TakahiroWakasugi1,EtsujiSaji1,FumihiroYanagimura1,3, MarikoHokari1,KaoriYanagawa1,MasatoyoNishizawa4, OsamuOnodera1,IzumiKawachi1,2
1 Department of Neurology, Brain Research Institute, Niigata University, Japan, 2 Comprehensive Medical Education Center, Niigata University School of Medicine, 3 Department of Neurology, NHO Niigata Hospital, 4 Niigata University of Health and Welfare
Objective:Multiple sclerosis （MS） and neuromyelitis optica spectrum disorder （NMOSD）
are inflammatory autoimmune diseases of the CNS. The aim of this study was to identify progression of cerebral lesions and volume in a Japanese cohort of MS, in compared to NMOSD.Methods:We performed a longitudinal study of cognition, and cerebral lesions and atrophy for 24 patients with MS and 16 patients with NMOSD. The Brief Repeatable Battery of Neuropsychological Test （BRBN） was conducted to evaluate cognitive function, and voxel based morphologyanalysis was performed to measure cerebral volume at baseline and at least 3 year-follow-up, respectively.Results:The mean follow-up periods for assessments were 5.3 years and 6.2 years in MS patients （male/female=7/17） and NMOSD patients （male/female=1/15）, respectively. During the follow-up study, the BRBN index （P<0.01） and some BRBN subitems of MS patients had significantlydeter ioratedcompared to NMOSD patients. The atrophy of cerebrum volume （P=0.02） had significantly progressed in MS patients in compared to NMOSD. In the gray matter of cerebrum, each atrophy of middle occipital gyrus, inferior occipital gyrus, lingual gyrus, fusiform gyrus and cingulate had significantly progressed. Volumes of cerebral lesion had not significantly been different between MS and NMOSD. At the baseline, there were some correlations between each BRBN score item and each volume of parts in the cerebrum in MS, in compared to NMOSD.Conclusions:This study indicated that cognitive impairment and cerebral atrophy are more deteriorated in MS, in compared to NMOSD.
Pe-07-8
EfficacyofMycophenolateMofetilinNMOSD:ASystematicReview
○SakdipatSongwisit1,PunchikaKosiyakul1,JirapornJitprapaikulsan1,2, SasitornSiritho1,2,NarapornPrayoonwiwat1,2,
PatompongUngprasert3
1 Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, 2 Siriraj Neuroimmunology Center, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, 3 Clinical Epidemiology Unit, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
Objective Mycophenolate mofetil （MMF） is a commonly prescribed medication for relapse prevention in patients with neuromyelitis optica spectrum disorders （NMOSD）. However, data on its efficacy are still relatively limited. This study aims to review data on the effects of MMF on disease severity and disability among patients with NMOSD using systematic review technique. Methods Published peer-reviewed studies were independently searched from EMBASE and OVID/Medline database by two investigators. Inclusion criteria were cohort studies of NMOSD patients treated with MMF that reported treatment outcomes, using either Annualized Relapse Rate （ARR） or Expanded Disability Status Scale （EDDS）, before and after treatment. Case reports, case series with less than 3 patients, and reviews were excluded. Results We identified 563 potentially relevant articles from the two databases.
After two rounds of review, 15 eligible studies with 839 patients were identified. At least 712 patients （85%） were aquaporin-4 immunoglobulin seropositive. Median follow-up time of all studies was greater than 12 months. All 15 studies showed ARR reduction comparing pre- and post-treatment, in which statistical significance was reached in 13 studies. Of 12 studies analyzing EDSS, 9 showed significant improvement of EDSS, 1 revealed non-significant improvement of EDSS, 1 reported no EDSS change, and 1 showed non-significant increase in EDSS （by one point）. Conclusions This systematic review suggests that MMF could be used as a preventive therapy for NMOSD that is associated with improvement of ARR and EDSS.
Pe-07-9
EfficacyofPlasmaexchangeinNMOSD:A SystematicReviewandMeta-analysis○PunchikaKosiyakul1,SakdipatSongwisit1,PatompongUngprasert2, SasitornSiritho1,3,NarapornPrayoonwiwat1,3,
JirapornJitprapaikulsan1,3
1 Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, 2 Clinical Epidemiology Unit, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, 3 Siriraj Neuroimmunology Center, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
Objective Plasma exchange （PLEX） is a commonly utilized rescue therapy for severe neuromyelitis optica spectrum disorders （NMOSD） attacks, although data on its efficacy remain relatively unclear. The current systematic review and meta-analysis was conducted to further investigate the efficacy of PLEX for NMOSD attacks. Methods Systematic review was performed using EMBASE and OVID/Medline database. Inclusion criteria were （1）
cohort studies of NMOSD patients treated with PLEX in acute phase that （2） reported treatment outcomes using Expanded Disability Status Scale （EDSS） before and after the therapy. Case reports, case series less than 3 patients, and reviews were excluded. Results A total 1,395 unique articles were identified from the two databases. After two rounds of review conducted independently by two investigators, 14 studies （n = 291 and greater than 191
（65.6%） patients were aquaporin-4 immunoglobulin seropositive） met the inclusion criteria and were included into the meta-analysis. Immediately after treatment, PLEX therapy resulted in a significantly decreased EDSS with the pooled mean difference （MD） of 0.91 （95%
CI, 0.3 to 1.52, I2=72%） comparing pre-treatment to post-treatment. At follow-up （6 months to 1 year）, patients who received PLEX therapy continued to have a lower post-treatment EDSS with the pooled MD of 2.21 （95% CI, 1.57 to 2.86, I2=40%） Conclusions This meta-analysis suggests that PLEX therapy is effective in NMOSD attack that is associated with improvement of disability status immediately after treatment and during follow-up period.
Pe-07-6
withdrawn一 般 演 題
ポ ス タ ー （ 英 語 ）
Pe-07- 5
withdrawnPe-08-6
Transplantationofcapillarystemcellsimproves skeletalmuscleregenerationinmusculardystrophy○KoheiKano1,JunSawada1,ArisaYamamoto1,AsukaAsanome1, HisakoEndo1,TsukasaSaito1,NaoyukiHasebe1,Jun-ichiKawabe1,2
1 Aasahikawa medical University, Department of Medicine, Division of Cardiovascular, Respiratory and Neurology, Japan, 2 Aasahikawa medical University, Department of Biochemistry
Background & Purpose: Satellite cells （SCs） are key stem cells to regenerate skeletal muscles. However, recent studies demonstrate that genetic deletion of SCs does not affect muscle mass during their life span. Alternative skeletal muscle stem cells except SCs may exist to maintain skeletal muscles. We have identified multipotent EphA7-positive perivascular cells, namely capillary stem cells （CapSCs） from microvessels of peripheral tissues including skeletal muscles. In this study, we investigate skeletal muscular regenerative potency of CapSCs using muscle injury and muscular dystrophy models. Methods &
results: Mouse CapSCs and control cells, i.e. adipose stromal cells （ASCs） were isolated from subcutaneous adipose tissues of transgenic mice. When GFP-labeled CapSCs or ASCs were co-cultured with C2C12, mouse myoblast cells under muscle differentiation condition, the number of GFP-positive differentiated myofibers was significantly increased in CapSCs compared to ASCs. CapSCs or ASCs were transplanted into cardiotoxin-mediated damaged gastrocnemius or severe muscular dystrophy （mdx/urotphin gene deletion） mice. At 3 weeks after cell transplantation, GFP-positive microvessels and dystrophin+myofibers were well observed in CapSCs, but not ASCs. Transplantation of CapSCs significantly increased muscle weight, volume and walking distance, compared to ASCs. Conclusion: CapSCs have potent regenerative potency, i.e. myogenesis and angiogenesis, suggesting that CapSCs are one of skeletal muscle stem cells.
Thus, CapSCs would be attractive therapeutic tool for muscle dystrophy.
Pe-08-8
PrevalenceofNormalSomatosensoryEvoked PotentialinSubacuteCombinedDegeneration○Sung-juHsueh
Department of Neurology, National Taiwan University Hospital Yun-Lin Branch, Taiwan
Objectives Vitamin B12 deficiency is known to cause subacute combined degeneration. Electrophysiological studies, such as somatosensory evoked potential （SSEP,） could help localize of the structures involved. However, in some patients, despite present with significant symptoms, may still have normal findings on SSEP. We would like to study the prevalence of such clinical-electrophysiological discrepancy. Methods Records of patients admitted to the Neurology service of a single medical center in the past 3 years were analyzed. The inclusion criteria are: 1. Presence of myelopathy, as defined by clinical or radiological features. 2. Presence of vitamin B12 deficiency confirmed by serum biochemistry test. 3. No other causes of myelopathy are identified.
The results of nerve conduction study, magnetic resonance study, and SSEP studies are analyzed. Results 11 patients （4 female and 7 male） are included for analysis. The average age of patients is 52.09+/-18.07 years old. The cause of vitamin B12 deficiency was atrophic gastritis in 1 case, autoimmune gastritis in 1 case, Nitrous Oxide intoxication in 2 cases, vegetarian diet in 2 cases, and unknown in 5 cases. Peripheral neuropathy or radiculopathy was identified in 8 patients. 3 patients （27.3%） have normal SSEP in the upper and lower limbs, despite having clinical findings compatible with posterior column degeneration. Conclusion SSEP may remain normal in patients with posterior column degeneration caused by vitamin B12 deficiency, even in patients with significant clinical presentation.
Pe-09-1
Alargecohortstudyoftick-borneencephalitis inHokkaido~Itwasneverararedisease○IkukoTakahashi-iwata1,IchiroYabe1,KatsunoriEguchi1, MasahiroWakita1,AzusaNagai1,ChikaSato1,RyoujiNaganuma1, ShinichiShirai1,MasaakiMatsushima1,KentaroYoshii2, HidenaoSasaki1
1 Department of Neurology, Hokkaido University, Japan, 2 Laboratory of Public Health, Faculty of Veterinary Medicine, Hokkaido University [Objective] Tick-borne encephlitis virus （TBEV） is the cause of encephalitis （TBE）
and a few cases reported with poor prognosis have been localized in Japan, especially Hokkaido. IgG and IgM-ELISA are new detection methods using subviral particles
（SPs） as substitutes of the pathogenic virus which enable the screening of TBEV safely. We analyzed serum collected in our institution and investigated the presence of TBE. [Methods] The serum from 2,000 patients with various neurological disorders including central nervous system infections along with 247 healthy controls examined in our department were analyzed with IgG and IgM-ELISA and the positive samples were neutralization tested. [Results] Sixteen patients and one control showed a positive reaction either of IgG or IgM-ELISA, and also from the neutralization tests. The average age of the 17 cases was 57.2, their dwellings were ubiquitous, spread throughout Hokkaido. Nine cases were clinically diagnosed as meningitis, encephalitis and myelitis.
The cell proliferation of cerebrospinal fluid was shown in 8 cases and elevated protein was observed in 7. There were five patients with positive IgM-ELISA, especially two of them which showed a strong value in the neutralizing antibody. These 5 cases showed no other infectious proof or autoimmune antibody, and were interpreted to be probable acute TBE, and all of them showed a good prognosis. [Conclusion] There was more mild or treatment-effective TBE. We suggest that the epidemiology and pathophysiology of TBE should be viewed more broadly than the concept what we already know.
Pe-09-2
Shorttermprognosisofacuteencephalitis aboutelderlypatients○TatsuoIhara1,KazuyoshiShinpo2
1 Department of Neurology, Otaru General Hospital, Japan, 2 Department of Neurology, Hokkaido Neurosurgical Memorial Hospital
[Objective]Currently, we heve more opportunities for treating aged encephalitis patients. Although many cases of geriatric encephalitis have a poor prognosis, there are a few cases with a good prognosis. We retrospectively studied our cases focusing on short term prognosis.[Methods]We reviewed ten cases of admitted between April 2014 and October 2019. All the patients were aged between 60 to 80 years.[Results]Out of 10 cases, two patients died. Both patients presented status epilepticus seizures. One patient was affected with hyperglobulinemia, and probable blood disease, required intensive care and hemodialysis. Marked fluctuation was observed in the blood pressure of the other patient. Four of the patients, including one brainstem encephalitis, were bedridden. These patients did not recover despite undergoing antiviral therapy.
The cause might have been a delayed diagnosis or persistent hyperthermia requiring antipyretic treatment including steroid. Magnetic resonance imaging
（MRI） results revealed frontal or bilateral lesions. Among the four patients with a good prognosis, the clinical course was mild. The lesion on MRI scan was rather small or limited in the temporal region. The antiviral antibody test and the cerebrospinal fluid examination did not reveal any specific findings.
[Conclusions]Early diagnosis and antiviral therapy are critical for acute encephalitis patients. In elderly patients the prognosis is variable. Proper intensive care is mandatory including prevention of seizures. Additionally, a differential diagnosis of limbic encephalitis should be considered.
Pe-09-3
Possiblepleocytosisinpatientswithout meningealirritationsigns○SaoriAdachi-Abe,ToshikiUchihara,RyotaAmano,YokoMachida, SatoshiZeniya,HiroakiYokote,ShutaToru
Nitobe Memorial Nakano General Hospital, Japan
[Objective] Meningeal irritation signs are clinical clues to suspect meningitis in patients with headache and fever. Are these signs being powerful enough to exclude meningitis only by their absence? Based on the analysis of patients who underwent lumbar puncture （LP）, we aimed to find out the factors leading discrepancies between meningeal irritation signs and cerebrospinal fluid pleocytosis. [Methods] We conducted a retrospective review on 83 patients （97 exams）, who underwent LP in our hospital from April to October 2019, 41 patients were clinically suspected of meningitis. Meningeal irritation signs （Jolt accentuation, Neck flexion test, Kernig sign, Brudzinski sign, and Eye ball tenderness evaluated in each patient） were analyzed in reference to cerebrospinal fluid test results and final diagnosis. Pleocytosis was defined as the number of cells 5 /μL or more. [Results] In 41 patients （21 men, average 43 years old.）, 11 patients showed pleocytosis, and 5 of them were negative for any meningeal irritation signs. Four of them took analgesics, and two patients had preceding varicella zoster virus （VZV） infection. [Conclusions] Absence of meningeal irritation signs in these VZV meningitis patients may be explained if VZV involves preferentially pain-insensitive parenchyma rather than meninx.
As with patients on analgesics, pleocytosis is possible even in the absence of meningeal irritation signs, when LP may be considered.