5月20日(金）

ポスター (英語)

521

-20日

㈮ポスター

（英語) Pe-038-1

Withdrawn

Pe-038-2

Cortical infarction manifested by pure sensory loss of ulnar-sural distribution:

report of two cases

Taipei Municipal Wanfang Hospital, Taipei Medical University

○Chung Han Yang，Hao Wen Teng

Objective Vascular pathology involving the cerebral cortex or thalamus sometimes produces paresis mimicking peripheral neuropathy. Pure sensory loss in the distribution of peripheral nerve or radicular pattern caused by cerebral deficits, however, is very rare. Our report describes two young patients having unusual manifestation of cortical infarcts, which presented pure sensory disturbance in ulnar-sural distribution.Methods We studied a 49-year-old and a 20-year-old otherwise healthy woman, both of whom experienced numbness and tingling sensation in the distribution of right ulnar and sural nerve. The blood test, spinal X-ray, and nerve conduction study were within normal range. The brain magnetic resonance imaging (MRI) scan and cerebral digital subtraction angiography (DSA) were performed to investigate cerebral lesions in both cases.Results The diffusion-weighted imaging and T2 fluid-attenuated inversion recovery (T2-FLAIR) of a MRI scan of the older patient demonstrated several small infarcts in the left frontoparietal cortex. And the T2-FLAIR MRI of the younger patient revealed infarcts in the similar locations. The conventional vascular risk factors were absent in our cases. With the cerebral DSA, one of our patients was diagnosed as having dissection in M1 segment of left middle cerebral artery, and the other, hypoplasia in left proximal internal carotid artery.Conclusions Cortical infarction should be considered in a patient, even in young subject, who develops multi-sensory loss with peripheral nerve or radicular distribution on the same side of the body.

Pe-038-3

Poststroke Mania affecting Painting Style of Professional Artist Hallym university sacred heart hospital

○Eunjoo Rhee，Young Eun Kim，Byung-Chul Lee

Purpose: Post stroke neuropsychiatric syndrome is common. Mania can be a consequence of stroke but is not common. Here,we report a professional artist whose painting style dramatically changed with manic illness from a recent stroke. Method: A 58-year-old Korean man who had worked in Russia as a professional painter visited an emergency room due to sudden onset of dysarthria and left side weakness when he woke up in the morning. On neurologic examination, dysarthria, left facial palsy and left hemiparesis (motor grade IV/IV) were observed. The brain MRI revealed a territorial ischemic lesion with proximal occlusion of the inferior division of the right middle cerebral artery.

Result: 2 weeks after symptom onset, although his neurological deficits were much improved, he became very erratic, aggressive, talkative, hyperenergetic and lost the desire to sleep, staying up all night and continuously drawing art pieces consisting of a human face. Furthermore, his wife noted that his style of painting absolutely transformed. His previous artwork showed complementary and subtle color schemes, with well-defined heads and figures using sharp, crisp lines. On the other hands, after strple, the drawings appeared cruder, with barbaric looking figures and aggressive tones, in contrast to his prestroke modest, polished looking paintings. Conclusion: In this case, the MRI findings showed the involvement of the inferior temporal lobe including the amygdala. Dysregulation of this pathway may explain the alteration in his mood, and the subsequent change in painting style in this patient.

Pe-038-4

Ocular tilt reaction or alternating skew deviation caused by a localized cerebellar hemorrhage

1Department of Neurology, Tokyo Metropolitan Health and Medical Corporation Toshima Hospital，²Department of Neurology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital

○Hiromasa Tsuda^1,2，Keiko Takahashi¹，Kozue Tanaka²

[Introduction]Ocular tilt reaction (OTR) is defined as a triad of skew deviation, conjugate ocular torsion and head tilt. Alternating skew deviation (ASD) is the side of the higher eye changes depending on whether the gaze is directed to the left or to the right side. We note a first case of complete OTR and a very rare case of ASD due to a localized cerebellar hemorrhage, respectively. [Patients] Patient 1 was a 78-year-old man with essential hypertension suddenly developed complete OTR due to a localized hemorrhage in the vicinity of the left nodule. Patient 2 was a 76-year-old woman with essential hypertension abruptly developed ASD with abducting eye hypertropia due to a symmetrical hemorrhage in the vicinity of the nodulus and uvula. There was not brainstem lesion or hydrocephalus.[Discussion]The utricular signals are relayed from the vestibular nuclei, medullary reticular formation, inferior olive, and lateral reticular nucleus to the nodule and uvula in the cerebellum. In patient 1, damage to the left nodule might cause rightward conjugate ocular torsion and rightward head tilt. Moreover, concomitant skew deviation (CKD) is a common symptom in cerebellar lesion. Thus, complete OTR might develop based on both etiologies. In patient 2, bilateral CKD due to symmetrical damage to the cerebellum might induce ASD.[Conclusion]Localized cerebellar lesion involving unilateral nodule may induce complete OTR, while symmetrical localized cerebellar lesion may cause ASD.[References]Patient 1 was reported in Intern Med 2014;53:2251-4, and patient 2 in Intern Med 2012;51:2793-6.

Pe-038-5 WIthdrawn

Pe-039-1 WIthdrawn

20日

㈮ポスター

（英語)

Pe-039-2

PEDIATRIC ISCHEMIC STROKE SECONDARY TO POST-VARICELLA INFECTION AND PROTEIN S DECIFIENCY

PHILIPPINE CHILDREN’S MEDICAL CENTER

○Ariel C. Rabanes，Marilyn H. Ortiz

Objective: To present a case of pediatric stroke secondary to post-varicella infection and protein S deficiency.Introduction: Varicella or chickenpox is a common, usually benign, disease of childhood caused by varicella-zoster virus (VZV). VZV infections can induce cerebral angiopathy that affects most often the middle cerebral artery. We report the case of a male child from the Philippines who presented with acute neurologic deficits attributed to contralateral cerebral infarction, 12 months after VZV infection.Method: Case Report/Basic ResearchResult: Magnetic Resonance Imaging and Angiography (MRI/MRA) revealed ischemic infarcts involving the segment of left middle cerebral artery..

Protein S was also deranged.Conclusion: Ischemic stroke is the most common cerebrovascular disease, most often due to atherothrombotic diseases and uncommonly by disorders of hypercoagulation. Varicella infection has also been recognised as an important etiological factor in childhood stroke. The disorders of coagulation leading to thrombotic disorders are approximately 1％ of all ischemic strokes and 4-8％ of young strokes.Varicella infection is a common infection and it is believed to be a benign condition in children. However, the association between varicella and acute ischemic stroke in childhood appears to be significant. Both cerebrovascular disease and thrombotic abnormalities are believed to be implicated.

Pe-039-3

Unilateral medial thalamic infarct presenting with bilateral vertical gaze palsy: A case report

National Neuroscience Institute, Singapore General Hospital Campus

○Youjiang J. Tan，Clement Wu，Ee Wei Lim，Chun Wai Yip Mesencephalic infarcts resulting in supranuclear vertical gaze palsies are well-described and understood. In contrast, supranuclear vertical gaze palsies due to isolated unilateral medial thalamic infarcts, in the absence of involvement of the midbrain, are infrequent and poorly characterised. Consequently, we report the case of a 65 year-old Chinese man who presented acutely to our institution with bilateral vertical gaze palsy due to an infarct involving the right medial thalamus, without the involvement of the midbrain, demonstrated on Magnetic Resonance Imaging (MRI). The control centres of vertical gaze appears more expansive than previously thought. Whether the thalamus functions as an integral and essential component the control centre of vertical gaze, or as an unfortunate bystander remains an exciting question which future pathological and imaging studies will serve to answer.

Pe-039-4

Clinical features of patients with motor fluctuations before intravenous thrombolysis

1Department of Neurology, Yokohama City Minato Red Cross Hospital，

2Department of Neurology and Neurological Sciences, Tokyo Medical and Dental University

○Toshiro Kanazawa¹，Yurie Nose¹，Yutaro Asami¹，Jin Nonami¹， Masahide Iijima¹，Hiroaki Tanaka¹，Takanori Yokota²

OBJECTIVE: The clinical features of patients with marked clinical fluctuations before the intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) were reviewed to find room for improvement on the thrombolysis with rt-PA.METHOD:

Records of successive 81 stroke patients from 2010 to 2015, receiving intravenous thrombolysis with rt-PA were retrospectively reviewed.RESULTS: Thirteen cases (16％) showed clinical fluctuations before the intravenous thrombolysis with rt-PA: 4 with diagnosis of BAD, 3 atherothrombotic infarction and 6 cardioembolism. Prominent motor improvement in the course of rt-PA administration was observed in 12 out of 13 cases: all 4 cases of BAD, all 3 cases of atherothrombotic infarction, and 5 cases out of 6 cardioembolism. However, 3 out of 4 cases of BAD and 1 out of 3 cases of atherothrombotic infarction showed motor worsening again after the end of rt-PA administration without bleeding or blood pressure drop. Motor function was not worsened again in any cases of cardioembolism.CONCLUSION: Occluded arteries of any brain infarction with clinical fluctuations was highly recanalized by administration of rt-PA, but re-occlusion was observed in the BAD cases (75％) and atherothrombotic cases (33％). Narrow recanalized artery, such as perforating branches with atherosclerotic changes at their entrance, can be easily re-occluded. In these cases, administration of rt-PA together with antithrombotic therapy at the same time may be beneficial with less risk of bleeding.

Pe-039-5

Risk and adverse outcomes of stroke in patients with liver cirrhosis: two nationwide studies

1School of Medicine, Taipei Medical University, Taipei, Taiwan，²Department of Anesthesiology, Taipei Medical University Hospital, Taipei, Taiwan，³School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung, Taiwan

○Liao Chien-chang^1,2，Ta-Liang Chen^1,2，Chun-Chuan Shih³

Background:The association between liver cirrhosis (LC) and risk of stroke was not completely understood. This study evaluated stroke risk and post-stroke outcomes in patients with LC.Methods:We identified 3955 adults aged 20 years and older newly diagnosed with LC using the Taiwan National Health Insurance Research Database from 2000 to 2005. Comparison cohort consisted of 15820 adults without LC randomly selected by frequency matching in age and sex. Events of new-onset stroke were identified from medical claims during the follow-up period in 2000-2009. Adjusted hazard ratios (HR) and 95 ％ confidence interval (CI) of stroke associated with LC were calculated in the multiple Cox proportional hazard model. Another nested stroke cohort study of 21267 hospitalized stroke patients analyzed for adjusted odds ratios (ORs) and 95 ％ CIs of adverse events after stroke among patients with and without LC between 2000 and 2010.Results:The incidences of stroke for people with and without LC were 6.1 and 4.3 per 1,000 person-years, respectively. Compared with non-cirrhotic cohort, the adjusted HR of stroke was 1.55 (95 ％ CI 1.28-1.87) for LC patients. Previous LC was associated with risks of epilepsy (OR 1.30, 95％ CI 1.09-1.56), admission to intensive care unit (OR 1.23, 95％ CI (1.14-1.32), and mortality (OR 1.83, 95 ％ CI 1.63-2.05) after stroke.Conclusion:LC was associated with higher risk of stroke and patients with LC had more complications and mortality after stroke. Stroke prevention and attention to post-stroke adverse events is crucial for this susceptible population.

Pe-039-6

Cerebral Amyloid Angiopathy in Post-transplant Patients with Hereditary ATTR Amyloidosis

1Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine，²Institute for Biomedical Sciences, Shinshu University，

3Jisenkai Brain Imaging Research Center

○Yoshiki Sekijima^1,2,3，Yazaki Masahide^1,2，Kazuhiro Oguchi³， Tsuneaki Yoshinaga¹，Ikeda Shu-ichi^1,2

Objective:Liver transplantation markedly improves survival in hereditary ATTR amyloidosis.

However, the prolonged disease duration induces de novo central nervous system (CNS) amyloidosis, ATTR-type cerebral amyloid angiopathy (CAA), as choroid plexus continues to produce variant transthyretin. We investigated the prevalence and clinical features of post-transplant CNS symptoms in hereditary ATTR amyloidosis patients and their Pittsburgh compound B (PIB) -positron emission tomography (PET) imaging correlates.Methods:We monitored prevalence and type of CNS symptoms in 53 consecutive post-transplant patients with hereditary ATTR amyloidosis.¹¹C-PIB-PET was performed in 15 patients with various disease durations. We also analyzed pathological and biochemical characteristics of ATTR amyloid deposition in the brain of a post-transplant patient.Results:Transient focal neurological episodes (TFNEs) attributed to ATTR-type CAA were found in 11.3％ of post-transplanted hereditary ATTR amyloidosis patients. TFNE occurred on average 16.8 years after onset of the disease.

Patients with longer duration of illness (≧10 years) showed increased¹¹C-PIB retention in the brain. In the autopsy case, ATTR amyloid deposition was mainly localized to leptomeningeal vessels and leptomeninges. Amyloid fibrils in the brain were almost completely composed of variant TTR.Conclusions: TFNE due to ATTR-type CAA occurred frequently in post-transplant patients with long disease durations.¹¹C-PIB-PET is a useful diagnostic tool for ATTR-type CAA.

Pe-040-1

Risk of Stroke after Uvulopalatopharyngoplasty in Patients with Obstructive Sleep Apnea

1Department of Anesthesiology, Taipei Medical University Hospital, Taiwan，

2School of Medicine, Taipei Medical University

○Liao Chien-chang^1,2，Chen Ta-Liang^1,2

Objective:The aim of this study is to investigate the effects of UPPP on reducing risk of stroke in patients with OSA.Methods:Using Taiwan’s National Health Insurance Research Database, we conducted a retrospective cohort study of 10339 patients with new OSA between January 1, 2004 and December 31, 2009. The incident stroke was identified during the one-year follow-up period in patients with and without receiving uvulopalatopharyngoplasty (UPPP) . The rate ratios (RRs) and 95％ confidence intervals (CIs) of stroke associated with receiving UPPP in patients with OSA were calculated in multivariate Poisson regression.Results: The one-year incidences of stroke for OSA patients with and without UPPP were 1.06％ and 5.14％，respectively.

Patients with OSA receiving UPPP had lower risk of stroke compared with those without UPPP (RR, 0.45; 95％ CI, 0.33-0.61). The decreased risk of stroke following UPPP was observed in both sexes and all age groups. In the stratified analysis of medical conditions, the RR of stroke associated with UPPP for patients with no, one and more than two medical conditions were 0.28 (95％ CI 0.12-0.68), 0.39 (95％ CI 0.21-0.73), and 0.63 (95％ CI 0.43-0.93), respectively.Conclusions:Patients with OSA who received UPPP had lower risk of stroke within one year after surgery compared with patients not receiving UPPP. Clinical physicians could have more evidence to persuade patients to receive surgical intervention, especially those who have severe OSA symptoms or do not acquire adequate symptom relief under conservative treatments.

522

-20日

㈮ポスター

（英語)

Pe-039-2

PEDIATRIC ISCHEMIC STROKE SECONDARY TO POST-VARICELLA INFECTION AND PROTEIN S DECIFIENCY

PHILIPPINE CHILDREN’S MEDICAL CENTER

○Ariel C. Rabanes，Marilyn H. Ortiz

Pe-039-3

Unilateral medial thalamic infarct presenting with bilateral vertical gaze palsy: A case report

National Neuroscience Institute, Singapore General Hospital Campus

Pe-039-4

Clinical features of patients with motor fluctuations before intravenous thrombolysis

1Department of Neurology, Yokohama City Minato Red Cross Hospital，

2Department of Neurology and Neurological Sciences, Tokyo Medical and Dental University

○Toshiro Kanazawa¹，Yurie Nose¹，Yutaro Asami¹，Jin Nonami¹， Masahide Iijima¹，Hiroaki Tanaka¹，Takanori Yokota²

Pe-039-5

Risk and adverse outcomes of stroke in patients with liver cirrhosis: two nationwide studies

○Liao Chien-chang^1,2，Ta-Liang Chen^1,2，Chun-Chuan Shih³

Pe-039-6

Cerebral Amyloid Angiopathy in Post-transplant Patients with Hereditary ATTR Amyloidosis

1Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine，²Institute for Biomedical Sciences, Shinshu University，

3Jisenkai Brain Imaging Research Center

○Yoshiki Sekijima^1,2,3，Yazaki Masahide^1,2，Kazuhiro Oguchi³， Tsuneaki Yoshinaga¹，Ikeda Shu-ichi^1,2

Objective:Liver transplantation markedly improves survival in hereditary ATTR amyloidosis.

Pe-040-1

Risk of Stroke after Uvulopalatopharyngoplasty in Patients with Obstructive Sleep Apnea

1Department of Anesthesiology, Taipei Medical University Hospital, Taiwan，

2School of Medicine, Taipei Medical University

○Liao Chien-chang^1,2，Chen Ta-Liang^1,2

Objective:The aim of this study is to investigate the effects of UPPP on reducing risk of stroke in patients with OSA.Methods:Using Taiwan’s National Health Insurance Research Database, we conducted a retrospective cohort study of 10339 patients with new OSA between January 1, 2004 and December 31, 2009. The incident stroke was identified during the one-year follow-up period in patients with and without receiving uvulopalatopharyngoplasty (UPPP) . The rate ratios (RRs) and 95％ confidence intervals (CIs) of stroke associated with receiving UPPP in patients with OSA were calculated in multivariate Poisson regression.Results:The one-year incidences of stroke for OSA patients with and without UPPP were 1.06％ and 5.14％，respectively.

523

-20日

㈮ポスター

（英語) Pe-040-2

WIthdrawn

Pe-040-3

Gut dysbiosis is associated with exacerbated ischemic brain injury through systemic inflammation

1Department of Neurology, Juntendo University School of Medicine, Tokyo，

2Department of Neurology, Juntendo University Urayasu Hospital, Chiba，

3Probiotics Research Laboratory, Juntendo University Graduate School of Medicine, Tokyo，⁴Yakult Central Institute for Microbiological Research, Tokyo

○Naohide Kurita¹，Kazuo Yamasiro¹，Takuma Kuroki¹，Yuji Ueno¹， Ryota Tanaka¹，Takao Urabe²，Koji Nomoto^3,4，Takuya Takahasi^3,4， Hirokazu Tuji⁴，Takasi Asahara⁴，Yamashiro Yuichiro³，

Nobutaka Hattori¹

[Objective] systemic inflammation is one of the factors that aggravate the tissue damage in acute cerebral infarction.

Recent studies using diabetic mice have indicated that gut dysbiosis is associated with increased intestinal permeability and systemic inflammation. This study aimed to investigate the effect of gut dysbiosis on ischemic brain injury.[Methods] The composition of fecal gut microbiota was examined by the 16S rRNA-targeted RT-quantitative PCR, and plasma levels of cytokine and LPS were determined by ELISA in type 2 diabetic (db/db) mice and their nondiabetic control mice (db/+). Infarct volume, blood-brain barrier permeability, and neurological scores were measured in mice subjected to transient middle cerebral artery occlusion.[Results] The bacterial number of the Lactobacillus ruminis subgroup, Enterobacteriaceae, and Enterococcus were significantly higher in fecal samples of db/db mice than in those of db/+ mice. In addition, the plasma levels of interleukin-6 and LPS were significantly higher in db/db mice. Furthermore, db/db mice exhibited worse motor functions and larger increases in blood-brain barrier permeability, infarct volume and microglia counts around infarct areas. TLR4 was expressed in astrocytes and microglia. Brain of db/db mice showed increasing expression of TLR4, a receptor of LPS, and phosphorylated NF-κB that is involved in the downstream signaling pathway of TLR4. [Conclusions] Our study suggest that gut dysbiosis contributes to exacerbation of ischemic brain injury by induction of systemic inflammation.

Pe-040-4 withdrawn

Pe-040-5

Outcomes of Stroke Patients with Elevated Troponin I: A Systematic Review University of the Philippines - Philippine General Hospital

○Lennie Lynn Y. Chua，Ranhel C. De Roxas，

Ma. Epifania V. Collantes

Background. Stroke is the second leading cause of death and fifth leading cause of disease burden in the Philippines. About 20％ of deaths after ischemic stroke can be attributed to cardiac co-morbidities. Troponins are cardiac markers which are highly sensitive and specific for myocardial necrosis. The association between troponins and stroke has already been established; however its neurologic consequence is uncertain.Objective. The objective of this review is to determine the association of elevated troponin I with outcomes of patients with acute stroke, particularly death and neurologic disability.Methods. This is a systematic review including four studies evaluating the outcomes of adultpatients with acute ischemic and hemorrhagic stroke with elevated troponin I.Results. In 1849 patients, 8.5 to 18.8 percent have elevated troponin I. The risk of death andneurologic disability (modified rankin scale) is two to three times higher in those with elevatedtroponin I. The main limitation of this review is that the cut-off values for positive troponin levels are different for each of the studies. Also, the population is heterogeneous, composing ofhemorrhagic and ischemic stroke patients. The studies also differ in the clinical designs, thus theoutcomes are also difficult to compare.Conclusion. More studies are needed in order to determine the relationship of troponin I with outcomes of stroke patients.

Pe-040-6

Relation between LDL-C change and CAVI during treatment with pitavastatin Department of Neurology, School of Medicine Faculty of Medicine, Toho University, Tokyo

○Hideki Sugimoto，Shingo Konno，Hiroshi Nakazora，Mayumi Murata，

Hisao Kitazono，Tomomi Imamura，Masashi Inoue，Miyuki Sasaki，

Akihisa Fuse，Wataru Hagiwara，Mari Kobayashi，Hideo Kihara，

Toshiki Fujioka

[Objective]Hypercholesterolemia (HC) is a cerebral infarction (CI) risk factor. Higher LDL-cholesterol (LDL-C) levels activate more platelets, increasing the chances of thrombosis. The cardio-ankle vascular index (CAVI) is a known arteriosclerosis (ASVD) severity indicator. Previously we reported improvement of pitavastatin (Pit)-associated platelet activation markers (PAMs) regardless of the ASVD severity. Many reports have documented that CAVI and LDL-C are not directly related. We investigated the relation between Pit-associated LDL-C change and CAVI.[Methods]We examined in 21 patients with CI complicated with HC, who were receiving Pit (10 men, mean age 65.6 years). The patients were divided into two groups based on the LDL-C percentage change (high/low-LDL groups) to investigate the relation between Pit-associated (high/low-LDL-C change and CAVI.

Then they were divided into another two groups based on the median CAVI (high/low-CAVI groups) to investigate the LDL-C percentage change. Simultaneously, we investigated the relation between homocysteine (Hcy) and CAVI in 16 patients and percentage change in PAMs and CAVI in 12 patients.[Results]The CAVI was significantly higher in the low-LDL group (median -40％); the high-CAVI group showed more improved LDL-C level (p = 0.06). Hcy and CAVI tended to positively correlated. PAM percentage change and CAVI tended to negatively correlated.[Conclusion]The LDL-C level improved more in the high-CAVI group with a potential higher risk of recurrent CI. Potential physiological efficacy of Pit was demonstrated in treating severe ASVD.

Pe-040-7 WIthdrawn

20日

㈮ポスター

（英語)

Pe-041-1

Measuring the severity of ataxia using a triaxial accelerometer: a new assessment method

1Department of Neurology and Rheumatology, Shinshu University School of Medicine，²JA Nagano Koseiren Kakeyu-Misayama Rehabilitation Center Kakeyu Hospital，³Department of Brain Disease Research, Shinshu University School of Medicine，⁴Kissei Comtec Co., Ltd

○Akira Matsushima^1,2，Kunihiro Yoshida³，Hirokazu Genno⁴， Setsuko Matsuzawa⁴，Shu-ichi Ikeda¹

[Objective]The purpose of this study is to develop a method for assessment of ataxia with continuous variable calculated from the acceleration data using a triaxial accelerometer.

[Method]Fifty-six healthy controls and 54 SCA or MSA-C patients were enrolled. All the patients were ambulatory, but some needed a cane or walker on walking. A triaxial accelerometer was put on the median of L3 of the subjects. In gait assessment, the subjects repeated a 10-meter walk 12 times. Gait parameters including the velocity, step length, cadence, step regularity (SR), and degree of the body sway (BS) were measured. SR, and BS were defined based on previous reports. SARA score was recorded on the same day of the measurement. For calculating a composite value representing gait ability, principal component analysis (PCA) was used. Gait velocity, step length, cadence, SR and BS in the patients were used as the original variables in the PCA.[Result]As a result of PCA, the first principal component score (FPCS) was calculated for each subject. The FPCS was significantly different between the controls and patients (p ＜ 0.001). The FPCS was inversely proportional to the SARA score of gait in the patients. The FPCS was strongly correlated with the SARA score of gait and duration of disease (r = -0.64: p ＜ 0.001, r = -0.43: p = 0.001, respectively).[Conclusion]

Although a detailed verification of the usefulness and validity of the new scoring method is needed, a triaxial accelerometer can be clinically useful for quantitative assessment of ataxia.

Pe-041-2

Novel compound heterozygous mutations of SPG11 gene in spastic paraplegia with thin corpus callosum

Division of Neurology, Department of Internal Medicine, Jichi Medical University

○Haruo Shimazaki，Tohru Matsuura

[Background] Hereditary spastic paraplegias (HSPs) are a heterogeneous group of neurodegenerative disorders that show progressive spasticity in the lower extremities with variable additional symptoms. To date, more than 70 genetic loci (SPG) have been assigned in HSPs. HSP with thin corpus callosum (TCC) is a feature associated with many types of SPGs. We encountered a sporadic case of spastic paraplegia with thin corpus callosum. We tried to identify the causative gene mutation of this case.[Methods] A non-consanguineous family including one patient with TCC was examined. We performed whole-exome sequencing (WES) of the patient’s DNA and searched deleterious mutations of HSP genes in the WES result. Mutations were confirmed by Sanger sequencing and co-segregation study in this family.[Result] The patient noticed his gait difficulty at age 13. His gait disturbance was gradually worsened and wheel-chair bound at age 23. He had mental impairment. His brain MRI showed marked thin corpus callosum. We could identify a novel nonsense mutation in exon 6 and a missense one in exon 14 of SPG11 gene. We confirmed that these mutations were co-segregated within this family.[Discussion] SPG11 is the most common type of autosomal recessive (AR) HSP-TCC. SPG11 shows early-onset spastic paraplegia with thin corpus callosum and mental impairment. We identified novel nonsense mutation of SPG11 gene and this study showed that WES is one of the useful methods for search the causative gene mutations even in the sporadic cases with spastic paraplegia with TCC.

Pe-041-3

A clinical and neuropathological study on homozygous mutations with spinocerebellar ataxia type 6

1Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University，²The Center for Personalized Medicine for Healthy Aging, Tokyo Medical and Dental University，³Department of Neurology, Kawaguchi Kogyo General Hospital，⁴National Center for Neurology and Psychiatry

○Kazumasa Soga¹，Kinya Ishikawa^1,2，Tokuro Huruya³， Hidehiro Mizusawa^1,4，Takanori Yokota¹

[Objective] Spinocerebellar ataxia type 6 (SCA6) is an autosomal dominant cerebellar ataxia caused by a CAG repeat expansion in the α1A calcium channel gene (CACNA1A). The aim of this study is to clarify if there is a gene dosage effect in SCA6, by analyzing age of onset and the amount of calcium channel protein aggregation in the brain tissues. [Methods] A correlation between the number of CAG repeats and the age of onset was analyzed in 116 SCA6 patients including 3 homozygous cases. We had an opportunity to examine the first autopsy case with homozygous CAG repeat expansions. The expression of transcripts was analyzed with fragment analysis in the homozygous case and 2 heterozygous samples. The abundance of polyglutamine aggregation in cerebellar Purkinje cells was analyzed in the same homozygous and 2 heterozygous cases by immunohistochemistry using an antibody A6RPT-#5803 against the α1A calcium channel carboxy-terminus. [Results] The age of onset in homozygous patients tended to be earlier than heterozygous patients when analyzed among individuals with the same CAG repeat length in their expanded alleles. We detected stable expression of two expanded transcripts in the homozygous patient’s brain tissue. The amount of aggregation in this patient was not so abundant compared with heterozygous patients. [Conclusions] Gene dosage seems to influence the age of onset in SCA6. On the other hand, we found that the gene dosage effect was not clear in terms of the amount of protein aggregation.

Pe-041-4 withdrawn

Pe-041-5

FMRP and FMR1 mRNA expression in FXTAS and other neurodegenerative disease brain

1Department of Neurology, University of Tsukuba，²Division of Neurology, Department of Medicine, Jichi Medical University，³Division of Functional Genomics, Research Center for Bioscience and Technology, Tottori University

○Kazuhiro Ishii¹，Shinya Ishihara¹，Takuya Koide¹，Tohru Matsuura²， Kaori Adachi³，Eiji Nanba³，Yasushi Tomidokoro¹，Akira Tamaoka¹ [Objective] Greater than 200 CGG repeats elicits transcriptional silencing of the FMR1 locus, with markedly reduced FMR1 mRNA and FMR protein(FMRP) production. These expansions result clinically in fragile X syndrome (FXS). In contrast, repeat expansions in the premutation range between 55 and 200 CGG repeats cause of fragile X-associated tremor/ataxia syndrome (FXTAS) indicating intention tremor, gait ataxia, parkinsonism and cognitive impairment.

Unlike the FXS, permutation sized CGG repeats elicits enhanced FMR1 transcription. However this increase in FMR1 mRNA is paradoxically associated with a reduction in total and activity-dependent FMRP expression. To clarify the paradoxical expression of FMRP and FMR1 mRNA in the FXTAS brain, these were measured and compared with normal subject and other degenerative disease (AD, PD, ALS) . [Methods] Frozen brains (superior frontal gyrus) in RIPA buffer were suspended,and measured band density of FMRP by the Western blot(WB) using anti-FMRP antibody. The semi-quantified band levels demanded the ratio with the standard of FMRP. Similarly, the MAP2 and GFAP were quantified by WB and found the ratio with FMRP.

The FMRP ratio was compared with between normal, other degenerative diseases and FXTAS.

FMR1 mRNA was extracted from all part of brains and quantified by real-time PCR. [Results]

FMRP decreased in FXTAS, AD, PD, but not ALS. FMR1 mRNA did not change in all groups, but increased with FXTAS cerebellum. [Conclusions] A decrease in FMRP and increase of FMR1 mRNA in the cerebellum of the target organ were found in the FXTAS brain.

Pe-041-6

Effects of the overexpression of TFEB in cellular models of neurodegenerative diseases

Department of Neurology, University of Occupational and Environmental Health School of Medicine

○Hiroaki Adachi，Huang Zhe，Okada Kazumasa，Ohnari Keiko，

Hashimoto Tomoyo，Toyota Tomoko，Iwanaka Yukio

[Background] In chronic neurodegenerative disorders such as polyglutamine (polyQ), commonly observed phenotypes include the abnormal accumulation of disease-causing proteins and the formation of nuclear and cytoplasmic inclusions.

Macroautophagy is a set of bulk degradation processes in which cells form double-membrane vesicles, called autophagosomes, around a portion of the cytoplasm. These autophagosomes ultimately fuse with lysosomes, resulting in the degradation of their substrates. The transcription factor EB (TFEB) has been reported to regulate autophagy by upregulating genes that belong to the coordinated lysosomal expression and regulation (CLEAR) network, thereby controlling lysosomal biogenesis. We examined the effects of the overexpression of TFEB in cultured cell models of neurodegenerative diseases. [Materials and Methods] Cells were transfected using Lipofectamine 2000 with plasmids encoding mutant androgen receptor, huntingtin, ataxin-1, ataxin-3 and TFEB.[Results] The overexpression of TFEB decreased the expression of each causative protein in the neuronal cell models (p＜ 0.01). The expression of the autophagic marker LC-3 II was significantly elevated in the cells expressing TFEB (p＜ 0.01). HIKESHI enhances reduction in mutant proteins with TFEB (p＜ 0.01). Depletion of HIKESHI influences the turnover of mutant proteins.

[Conclusions] These findings demonstrated that the high expression of TFEB and HIKESHI induced autophagosome formation and enhanced the preferential degradation of the disease-causative proteins.

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