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Treatment with alteplase for acute ischemic stroke patients with an unknown time of onset is safe and effective. However, clinical trials have some selection bias. The purpose of this study was to clarify the efficacy and safety of alteplase treatment in patients with unknown time of onset in a real-world clinical setting.We included consecutive patients with acute ischemic stroke visited within 4.5 h of onset or symptom recognition. We divided patients into two groups: onset clear group (C-group) and unknown time of onset group (U-group). We treated patients with an unknown time of onset if the DWI-FLAIR mismatch was positive. We calculated the prevalence of alteplase treatment in each group and compared prognosis between the two groups.Six hundred thirty-two patients arrived within 4.5 h of onset or symptom recognition. Of these, 446 patients (71 %) were in the C-group and 186 (29 %) in the U group. Alteplase treatment was performed in 35 % of patients in the C group and in 18 % in the U group (p 0.001). Favorable outcomes at 90 days in patients treated with alteplase were comparable between the C group (52 %) and the U group (53 %) (p = 0.887). All hemorrhagic complications, including non-symptomatic hemorrhagic transformation, occurred in 11 of 157 patients (7 %) in the C-group and one of 34 patients (3 %) in the U-group (p = 0.696).In a real-world clinical setting, alteplase treatment was performed safe in 18% of patients with an unknown time of stroke onset based on patient selection using the DWI-FLAIR mismatch.

Objective Left ventricular (LV) thrombus is a rare condition in acute cerebral infarction. The prevalence and features of cerebral infarction with LV thrombus are unclear. We explored the features of cerebral infarction due to LV thrombus. Methods In this single-center retrospective study, we investigated consecutive patients with acute ischemic stroke admitted within seven days of the onset who had LV thrombus found by transthoracic echocardiography (TTE). First, we calculated the prevalence of LV thrombus in patients with cardioembolic stroke (CES). Second, we investigated the baseline characteristics, including the TTE findings and features of cerebral infarction due to LV thrombus. Results From June 2012 to January 2019, a total of 5,693 patients were enrolled. Of these, 1,408 (25%) patients were diagnosed with CES. Of these 1,408 patients with CES, 13 (0.9%) had LV thrombus indicated by TTE, with dilative cardiomyopathy, subacute myocardial infarction, and old myocardial infarction present in 1 (8%), 2 (15%), and 10 (77%), respectively. The ejection fraction (EF) was 48.9% (25.3-64.7%). The maximum longitudinal size of LV thrombus was 13.4 (0.97-38.1) mm, and there was no correlation between the size of the LV thrombus and the EF. Regarding the features of cerebrovascular infarction, major vessel occlusion was observed in 10 (77%) patients. Six (46%) patients were found to have good outcomes (modified Rankin Scale 0-2) at 90 days after the onset. Conclusion LV thrombus was seen in 0.9% of patients with CES. Many of the patients with LV thrombus had major vessel occlusion.

Although the assessment of nutrition is essential for stroke patients, detailed associations between nutritional status at admission, subsequent complications, and clinical outcomes in patients with acute intracerebral hemorrhage (ICH) are unclear. We aimed to elucidate these associations using the Controlling Nutritional Status (CONUT) score. Consecutive patients with acute ICH were investigated. Nutritional status was evaluated using the CONUT score, calculated from the serum albumin level, lymphocyte count, and total cholesterol level. Subsequent complications, such as hemorrhage expansion (HE) during the acute stage and aspiration pneumonia during hospitalization, were evaluated. Poor outcome was defined as a modified Rankin Scale score of ≥ 3 at 3 months. Of the 721 patients, 49 had HE, 111 had aspiration pneumonia, and 409 had poor outcomes. Patients with HE had significantly lower total cholesterol levels than those without HE. Patients with aspiration pneumonia had significantly lower albumin levels, lower lymphocyte counts, and higher CONUT scores than those without aspiration pneumonia. Patients with poor outcomes had significantly lower albumin levels, lower lymphocyte counts, lower total cholesterol levels, and higher CONUT scores than those with good outcomes. Multivariable logistic analysis showed that higher CONUT scores were independently associated with poor outcome (odds ratio, 1.28; 95% confidence interval, 1.09-1.49; P = 0.002) after adjusting for baseline characteristics, HE, and aspiration pneumonia. Each component of CONUT was a useful predictor of subsequent complications. Malnutrition, determined using the CONUT score, was independently associated with poor outcomes in patients with ICH after adjusting for these complications.

Associated factors of the Myasthenia Gravis Activities of Daily Living (MG-ADL) score were investigated in 55 patients who had had generalized MG for more than 5 years. In multivariate analysis, correlates of the MG-ADL score at the last follow-up were the total number of fast-acting treatments (FTs) (standardized regression coefficient 0.617，P0.001) and Myasthenia Gravis Foundation of America (MGFA) classification (standardized regression coefficient 0.227，P = 0.032) (F = 32.7，P0.001). In patients with a score of 5 or more on MG-ADL at the last follow-up, tendency as follows were seen: 1) early-onset (P = 0.002), 2) longer duration (P = 0.014), 3) high frequency of MGFA classification V (P = 0.017), 4) high frequency of the total number of FTs (P0.001), and 5) higher dose of prednisolone at the last follow-up (P = 0.003). MGFA V, early-onset without depending on E-L-T classification, or difficulty of reduction for high doses of prednisolone can be the target of novel treatment for MG, and future prospective study will be expected.

Objective The Suita score is used to predict the 10-year prognosis of developing coronary heart disease (CHD). This study examined the association between the Suita score and stroke recurrence within one year in Japanese patients who experienced first-ever ischemic stroke. Methods This prospective cohort study at a stroke center in Japan included patients who experienced first-ever acute ischemic stroke (AIS) or a transient ischemic attack (TIA). During hospitalization, the Suita score was measured as the main exposure. Patients with a ≥5% predicted CHD risk were classified into the high-risk group. The primary outcome was stroke recurrence within one year of the stroke onset. A multivariate Cox regression analysis was conducted and adjusted for confounding and prognostic factors. Results Among the 1,204 patients evaluated, 937 (78%) were classified as having a high risk of developing CHD. Stroke recurrence was observed in 66 patients during the follow-up period. In the multivariate analysis, after adjusting for confounding and prognostic factors, such as non-small vessel occlusion and prescription of lipid-lowering agents at the time of discharge, a ≥5% predicted CHD risk was associated with the 1-year stroke recurrence after the initial onset [adjusted hazard ratio (HR) =2.20, 95% confidence interval (CI) =1.00-4.91, p=0.049; adjusted HR=2.00, 95% CI=1.01-4.14, p=0.048; adjusted HR=0.42, 95% CI=0.24-0.73, p=0.002]. Conclusion The Suita score, adapted for use in ischemic stroke with the same mechanism, correlated with the short-term recurrence within one year. Our findings suggest that the Suita score may be useful for predicting the long-term prognosis of developing CHD as well as the short-term recurrence for patients with first-ever AIS and TIA.

Key Clinical Message Taste alteration is one of the complications of severe diabetes. It is important in diabetes treatment to assess taste alteration and perform dietary counseling, therapeutic exercise, and oral care. In this case, multidisciplinary clinical approach by medical staff was successful for a severely diabetic patient with dysgeusia.

Strains of Streptococcus mutans expressing the cell surface collagen-binding protein, Cnm, encoded by cnm (cnm-positive S. mutans), are associated with hypertensive intracerebral hemorrhage (ICH) and the occurrence of cerebral microbleeds (CMBs). Small diffusion-weighted imaging (DWI) hyperintensities in patients with acute ICH are also associated with CMBs. However, the association between cnm-positive S. mutans and DWI hyperintensities is unclear. Hence, this study aimed to investigate the association between cnm-positive S. mutans and DWI hyperintensities in patients with acute ICH.Patients with acute ICH were prospectively registered at three hospitals. Dental plaque specimens were collected within 4 days after admission, and cnm-positive S. mutans was detected using the polymerase chain reaction. Magnetic resonance imaging at 14 ± 5 days after admission was used to evaluate DWI hyperintensities and CMBs.A total of 197 patients were enrolled in this study. cnm-positive S. mutans was detected in 30 patients (15.2%), and DWI hyperintensities were observed in 56 patients (28.4%). Patients with cnm-positive S. mutans had a higher frequency of DWI hyperintensities (50.0% vs 24.6%; p = 0.008) and a higher number of CMBs (5.5 vs 1.5; p 0.001) than those without cnm-positive S. mutans. Multivariable logistic analysis revealed that the presence of cnm-positive S. mutans was independently associated with DWI hyperintensities (OR 2.38; 95% CI 1.01-5.61; p = 0.047) after adjusting for several confounding factors.This study found an association between the presence of cnm-positive S. mutans and DWI hyperintensities in patients with acute ICH.

Background and Purpose: Unilateral spatial neglect (USN) is often observed in ischemic stroke patients suffered their right parietal lobe. USN is an obstacle to undergo rehabilitation smoothly, then might influence the recovery of activities of daily living (ADL) after stroke. We aimed to clarify the association between the presence of USN after ischemic stroke and the ADL improvement. Methods: Consecutive patients with first-ever ischemic stroke and left limb paralysis who admitted to within 7 days from onset during February 2011 and March 2019 were included. Patients met the following criteria were excluded: mRS ≥3 before onset, NIHSS >15 on admission, without left limb paralysis, and missing NIHSS or functional independence measure (FIM) score on admission. Multiple regression analysis was performed to investigate the association between FIM efficiency score of acute phase and following factors: age, sex, acute reperfusion therapy (using an intravenous infusion of recombinant tissue plasminogen activator and/or endovascular therapy), FIM score on admission, and other clinical characteristics. All data were collected retrospectively using our electrical health record. Results: 721 ischemic stroke patients with left limb paralysis (320 women, median age 76) were included. Median FIM efficiency score was significantly lower in patients with USN than without USN (n=240, 481; 0.83 vs 1.63, respectively). Multiple regression analysis showed that USN, age, and acute reperfusion therapy were significant prognostic factors of FIM efficiency (coefficient and 95% confidence interval [CI]: -0.135 [-0.771 to -0.153], -0.106 [-0.022 to -0.002], and 0.224 [0.136 to 0.305], respectively). Conclusions: USN significantly influence the recovery of ADL after ischemic stroke. Clinicians should adequately evaluate USN after stroke and undergo USN-specific rehabilitation for them to optimize the effect of post-stroke rehabilitation. USN-specific rehabilitation might lead to better FIM efficiency.

Background We aimed to develop quality indicators (QIs) related to primary and comprehensive stroke care and examine the feasibility of their measurement using the existing Diagnosis Procedure Combination (DPC) database. Methods and results We conducted a systematic review of domestic and international studies using the modified Delphi method. Feasibility of measuring the QI adherence rates was examined using a DPC-based nationwide stroke database (396,350 patients admitted during 2013-2015 to 558 hospitals participating in the J-ASPECT study). Associations between adherence rates of these QIs and hospital characteristics were analyzed using hierarchical logistic regression analysis. We developed 17 and 12 measures as QIs for primary and comprehensive stroke care, respectively. We found that measurement of the adherence rates of the developed QIs using the existing DPC database was feasible for the 6 QIs (primary stroke care: early and discharge antithrombotic drugs, mean 54.6% and 58.7%; discharge anticoagulation for atrial fibrillation, 64.4%; discharge antihypertensive agents, 51.7%; comprehensive stroke care: fasudil hydrochloride or ozagrel sodium for vasospasm prevention, 86.9%; death complications of diagnostic neuroangiography, 0.4%). We found wide inter-hospital variation in QI adherence rates based on hospital characteristics. Conclusions We developed QIs for primary and comprehensive stroke care. The DPC database may allow efficient data collection at low cost and decreased burden to evaluate the developed QIs.

In myasthenia gravis (MG) patients on intravenous methylprednisolone (IVMP) therapy, initial deterioration should be carefully monitored because it may cause myasthenic crisis. The aim of this study was to investigate the onset, duration and related factors of initial deterioration from the first IVMP in MG patients.A total dose of IVMP in the first cycle of 750 mg or less, over 750 to 1500 mg, and over 1500 to 3000 mg was used in the analysis. Initial deterioration was evaluated in qualitative and quantitative evaluation and was defined as an increase of 2 or more points on the The Myasthenia Gravis Activities of Daily Living (MG-ADL) scale after the start of IVMP therapy in the quantitative evaluation.We enrolled 51 mainly mild MG patients. The mode of onset of initial deterioration from the first IVMP treatment was day 4 in the qualitative and quantitative evaluation. In addition, the mode of duration was 3 days. In multiple logistic regression analysis, factors related to initial deterioration were MGFA classification with overall disease duration up to just before IVMP and thymectomy before IVMP in both the qualitative and the quantitative evaluation (p .001). One to four cycles of IVMP improved the MG-ADL score at hospital discharge from that at the start of IVMP (p .001).Disease severity and thymectomy before IVMP are related to initial deterioration in MG patients. IVMP can be repeated after initial deterioration weekly in most patients.

Background There is no conclusive evidence regarding a causal relationship between periodontitis and atherosclerosis. In this study, we examined the microbiome in the oral cavity and atheromatous plaques from atherosclerosis patients with or without periodontitis to investigate the role of oral bacteria in the formation of atheromatous plaques. We chose four patients with and without periodontitis, who had undergone carotid endarterectomy. Bacterial samples were extracted from saliva on the tongue surface, from periodontal pocket (during the oral examination), and from the atheromatous plaques. We investigated the general and oral conditions from each patient and performed next-generation sequencing analysis for all bacterial samples. Results There were no significant differences between both groups concerning general conditions. However, the microbiome patterns of the gingival pocket showed differences depending on the absence or presence of periodontitis, while those of the saliva were relatively similar. The microbiome pattern of the atheromatous plaques was entirely different from that in saliva present on the tongue surface and gingival pocket, and oral bacteria were seldom detected. However, the microbiome pattern in atheromatous plaques was different in the presence or absence of periodontitis. Conclusion These results indicated that oral bacteria did not affect the formation of atheromatous plaques directly. However, the metabolic products of microbiome or the host inflammatory response might indirectly influence the composition of atheromatous plaques.

Background: Improving the quality of stroke care is an urgent issue worldwide. To facilitate the measurement of quality of stroke care in Japan, we aimed to develop the Close The Gap-Stroke initiative in the J-ASPECT Study. Methods and Results: Quality indicators (QIs) were developed by a multidisciplinary board between 2015 and 2017. The process involved a systematic review of domestic and international studies related to primary and comprehensive stroke care. Adherence rates for the defined QIs were calculated for 8,826 patients with acute ischemic stroke from 227 hospitals between 2013 to 2015. Seventeen and 12 measures were identified as QIs for primary and comprehensive stroke care (PSC and CSC), respectively. We analyzed adherence rates of all 17 QIs for PSC and 8 QIs for CSC related with acute ischemic stroke. We found NIHSS documentation (91.0 %), CT/MRI performed within 25min and 24hr (80.9 % and 99.1 %), evaluation of extracranial vascular imaging (90.4 %), treated in stroke unit (57.4 %), tPA administration (89.5 %), tPA performed within 1hr (37.4 %), early and discharge antithrombotics medication (75.1 % and 49.0 %), discharge anticoagulation for atrial fibrillation patients (76.2 %), discharge statin medication (32.7 %), discharge antihypertensive agents (54.3 %), deep vein thrombosis prophylaxis (34.5 %), early rehabilitation (57.0 %), dysphagia screening (76.6 %), smoking cessation (59.8 %) and stroke education (71.4 %) for primary stroke care; and median time to multimodal CT or MR brain and vascular imaging (33 min), proper endovascular recanalization (81.7 %), tPA before endovascular recanalization (65.7 %), TICI grade 2b/3 after endovascular recanalization (73.0 %), median time of door to puncture (105 min), symptomatic intracranial hemorrhage after thrombolytic or endovascular therapy (7.45 %), 90 days mRS documentation after thrombolytic or endovascular therapy (60.8 %), occurrence of complication within 24 hours of diagnostic neuroangiography (7.27 %) for comprehensive stroke care. Conclusion: This is a promising first step to measure the QIs related to primary and comprehensive stroke care at a national level in Japan.

Some patients with Guillain-Barré syndrome require respiratory management by tracheotomy and/or nutritional management by tube feeding; however, few studies have reported the follow-up course in these patients. The objective of this study was to investigate the follow-up course of tracheotomy and gastrostomy in patients with Guillain-Barré syndrome. The study subjects were 50 patients with Guillain-Barré syndrome (25 males, 25 females; mean age, 51.1 ± 18.7 years) who were admitted to the Hiroshima City Rehabilitation Hospital during the period from April 2008 to December 2015. We retrospectively reviewed the medical records to determine the presence or absence of tracheotomy and/or feeding tube, and the timing of withdrawal from these treatments. During the acute phase, 15 patients underwent tracheotomy and 14 underwent tube feeding management. A tracheotomy tube was inserted for 110 days or longer in five patients, and four of these five patients also had a gastrostomy tube inserted. Among the 14 patients in the tube feeding group, seven underwent nasal feeding and seven underwent percutaneous endoscopic gastrostomy. All patients had the nasal tube removed (mean duration of nasal tube placement, 62.1 ± 46.5 days); however, the gastrostomy tube could not be removed in two patients. Our findings indicate that patients in the acute phase of Guillain-Barré syndrome carry a relevant risk of long-term tube feeding and prolonged need of an artificial airway.

Background The importance of rehabilitation therapy in Parkinson's disease is well recognized. However, the effects of an inpatient rehabilitation program for advanced Parkinson's disease have not been fully investigated. Aim To assess the effects of intensive inpatient rehabilitation. Methods We enrolled 31 patients (mean age 69.5 ± 9.4 years; mean disease duration 8.8 ± 6.4 years) with advanced Parkinson's disease, without severe cognitive impairment. The median Hoehn–Yahr stage was IV. Patients received 2 h of individualized rehabilitation for 6–7 days each week for 1 month. At hospital discharge, patients and caregivers were instructed to continue daily exercise. Results Motor and total scores of Functional Independence Measures significantly improved between admission and discharge in patients with stage III and IV disease, but not stage V. There was no significant effect of Hoehn–Yahr stage on improvements in Unified Parkinson's Disease Rating Scale scores, (total, part I, II or III), cognitive Functional Independence Measures or Berg Balance Scale. Conclusion Intensive inpatient rehabilitation was effective even in advanced Parkinson's disease. Intensive inpatient rehabilitation, together with home and day-care exercise, might counteract the progressive motor decline in Parkinson's disease.

Background This study aimed to evaluate the diagnostic performance of the amount of physical, occupational, and speech therapy intervention and optimal timing necessary for activities of daily living (ADL) independence in patients with stroke. Method Patients (N = 441) with stroke admitted to the convalescent rehabilitation ward were classified into an early intervention or a nonearly intervention group on the basis of the duration from the date of onset to date of hospital admission. Logistic regression model was used to identify factors influencing independence in ADL in both groups. Cutoff point, likelihood ratio, and posterior probabilities for ADL independence were calculated, and diagnostic accuracy was evaluated for extracted factors. Results Results of logistic regression analysis revealed that age and physical and occupational therapy intervention amount provided during convalescent phase and Functional Independent Measure (FIM) motor score at admission significantly influenced independence in ADL at discharge from the hospital in the early intervention group (hospitalization date was 30 days or less). The cutoff point was 168 hours; positive likelihood ratio was 1.74; negative likelihood ratio was .78; and the posterior probability for the time spent by the therapist was 81.0%. FIM motor score at admission was the only factor extracted for the nonearly intervention group (hospitalization date was 31 days or more). Conclusion The ADL independence in patients with stroke admitted to convalescent rehabilitation ward during their convalescent phase cannot be determined simply on the basis of the amount of physical and occupational therapy they receive.

Objective The aim of the present study was to investigate the association of magnetic resonance imaging (MRI) findings and social activity with cognitive function in Japanese patients with multiple sclerosis (MS). Methods The Brief Repeatable Battery of Neuropsychological tests (BRB-N) was carried out in 184 Japanese patients with MS, and 163 controls matched for age, sex and education. MRI findings of cerebral, brainstem, and cerebellar lesions and social activities of MS patients were further examined. Results MS patients with higher numbers of cerebral lesions on MRI had lower scores in most BRB-N tests. BRB-N scores in the majority of tests were significantly lower in patients with brainstem and cerebellar lesions. Data from an analysis of variance model in which only the main effects of cerebral, brainstem and cerebellar lesions were hypothesized showed an association of cerebral lesions with decreased scores in all BRB-N tests, except symbol digit modalities test (SDMT) and paced auditory serial addition test (PASAT). In contrast, cerebellar lesions were associated with decreased SDMT and PASAT scores. Patients categorized as “unemployed because of MS” had lower BRB-N scores than other social activity groups. Lower SDMT scores had an effect on the “unemployed because of MS” group, whereas the Expanded Disability Status Scale had a significantly greater negative impact on patients in this social category. Conclusions Higher numbers of brain lesions on MRI could have an impact on cognitive function in patients with MS, and impairment of information processing appears significantly associated with cerebellar lesions. Cognitive impairment affects the employment status of patients with MS.

Background Clopidogrel is sometimes substituted for ticlopidine when cerebrovascular or cardiovascular patients develop hematologic abnormalities after ticlopidine treatment. However, the adverse event rate after the substitution to clopidogrel remains undetermined. Therefore, in this study, we aimed to define the risk of adverse events after substituting clopidogrel for ticlopidine without a washout period. Methods We prospectively enrolled patients older than 20 years who had a history of noncardioembolic strokes, including transient ischemic attacks, were treated with ticlopidine for at least 6 months. This study was conducted from August 26, 2008, when the first patient was enrolled, to January 16, 2012, the date of the last patient examination, at 8 active stroke centers in Hiroshima, Japan. We excluded patients who had severe disabilities, evidence of cardioembolic stroke, or history of a bleeding event. Each patient received clopidogrel (either 50 mg or 75 mg) once a day in place of ticlopidine without a washout period. Follow-up exams were scheduled within 12 months after the medication substitution. The primary end point of this study was adverse events of interest, including clinically significant reduced blood cell counts, hepatic dysfunction, bleeding, and other serious side effects. Results In this study, 110 patients were enrolled and analyzed in an intent-to-treat manner (modified intent to treat). Within the scheduled follow-up periods, 9 primary end point events were observed in separate patients. The primary end point events were observed at a rate of 8.4% per year (Kaplan–Meier method). At the time of enrolment, 16 patients met the exclusion criteria, of which 8 recovered from their abnormal hematologic results to the institutional normal limit after the substitution of ticlopidine for clopidogrel (57.4% per year). Conclusions The adverse event rates after the substitution of ticlopidine for clopidogrel is similar to the adverse event rates of patients who were initially treated with clopidogrel. The substitution of clopidogrel for ticlopidine should be considered for patients who develop hematologic abnormalities from ticlopidine treatment.

Demyelinating Charcot-Marie-Tooth disease (CMT) and chronic inflammatory demyelinating polyneuropathy (CIDP) are both demyelinating polyneuropathies. The differences in nerve enlargement degree and pattern at multiple evaluation sites/levels are not well known. We investigated the differences in nerve enlargement degree and the distribution pattern of nerve enlargement in patients with demyelinating CMT and CIDP, and verified the appropriate combination of sites/levels to differentiate between these diseases. Ten patients (aged 23-84 years, three females) with demyelinating CMT and 16 patients (aged 30-85 years, five females) with CIDP were evaluated in this study. The nerve sizes were measured at 24 predetermined sites/levels from the median and ulnar nerves and the cervical nerve roots (CNR) using ultrasonography. The evaluation sites/levels were classified into three regions: distal, intermediate and cervical. The number of sites/levels that exhibited nerve enlargement (enlargement site number, ESN) in each region was determined from the 24 sites/levels and from the selected eight screening sites/levels, respectively. The cross-sectional areas of the peripheral nerves were markedly larger at all evaluation sites in patients with demyelinating CMT than in patients with CIDP (p < 0.01). However, the nerve sizes of CNR were not significantly different between patients with either disease. When we evaluated ESN of four selected sites for screening from the intermediate region, the sensitivity and specificity to distinguish between demyelinating CMT and CIDP were 0.90 and 0.94, respectively, with the cut-off value set at four. Nerve ultrasonography is useful to detect nerve enlargement and can clarify morphological differences in nerves between patients with demyelinating CMT and CIDP.

Objective Neuromyelitis optica spectrum disorders (NMOSD) are immune-mediated chronic inflammatory disorders of the central nervous system that are predominantly characterized by attacks of optic neuritis and/or transverse myelitis. The aim of this study was to investigate the clinical rehabilitation course of patients with NMOSD. Methods We carried out a retrospective evaluation of 20 cases of NMOSD in which the patients underwent multidisciplinary inpatient rehabilitation intervention starting within 2 months after acute exacerbation. Rehabilitation outcomes were assessed using the modified Rankin Scale, the Expanded Disability Status Scale (EDSS), and the Functional Independence Measure (FIM). Results A total of 19 cases were finally included in this study. The average EDSS scores ranged from 5.9 to 7.1 during hospitalization. Lower age significantly correlated with improved EDSS scores. Changes in the EDSS score during rehabilitation varied in patients experiencing their first attack; however, improvements in the EDSS score of ≥ 1.5 were observed only in patients who had experienced two or less attacks. During rehabilitation, the FIM significantly improved from 81.4 to 101.7, with a gain of 20.3 and efficacy of 0.2/day. Conclusion Multidisciplinary rehabilitation may improve functional recovery after NMOSD attacks. Younger age and two or less attacks were associated with better outcomes in this study.

BACKGROUND AND PURPOSE: Although MBs, ICH, and LI are secondary to cerebral microangiopathy, it remains unclear whether the location of subsequent ICH/LI corresponds to the previous location of MBs. We performed this study to clarify the positional relationship between recurrent ICH/LI and previously detected MBs. MATERIALS AND METHODS: We evaluated patients with recurrent ICH/LI who had MBs, as shown on prior T2*-weighted MR imaging. We assessed retrospectively whether the location of recurrent ICH/LI corresponded to that of the prior MB. Patients with ICH were divided into the deep ICH group and the lobar ICH group, and the positional relationship between hematoma and previously detected MBs was evaluated. RESULTS: A total of 55 patients, including 34 with recurrent ICH and 21 with recurrent LI were evaluated. Although the location of the LI corresponded to prior MBs in only 1 patient (4.8%), the location of ICH corresponded to prior locations of MBs in 21 patients (61.8%) (OR, 32.3; 95% CI, 3.86–270.3; P < .001). Among the patients with ICH, the correspondence ratio was higher in the deep ICH group (19 of 24 patients, 79.2%) than in the lobar ICH group (2 of 10 patients, 20%) (OR, 15.2; 95% CI, 2.42–95.3; P < .002). CONCLUSIONS: The close positional association between recurrent ICH and prior MBs suggests that MBs represent hemorrhage-prone microangiopathy. In addition, different correspondence ratios between the deep ICH group and the lobar ICH group may be attributable to their different pathogenesis.

There are two distinct phenotypes of multiple sclerosis (MS) in Asians, optic-spinal MS (OSMS) and conventional MS (CMS). In 2004, we performed the fourth nationwide epidemiological survey of MS. The epidemiological features were reported elsewhere; here we report the characteristic features of patients with each MS phenotype, classified according to the clinically estimated sites of involvement and MRI findings. Among 1493 MS patients collated, 57.7% were classified as having CMS and 16.5% were classified as having OSMS. Based on MRI findings, MS patients were further subdivided into those with OSMS with or without longitudinally extensive spinal cord lesions (LESCLs) and those with CMS with or without LESCLs. Although disease duration did not differ significantly among the four groups, EDSS scores were significantly higher in patients with LESCLs than in those without LESCLs, irrespective of OSMS or CMS phenotype. Similar trends were found for the frequencies of bilateral visual loss, transverse myelitis, and marked CSF pleocytosis and neutrophilia. Increased IgG index, brain lesions fulfilling the Barkhof criteria and secondary progression were more commonly found in CMS patients than in OSMS patients, while negative brain MRIs were more commonly encountered in OSMS patients than CMS patients, irrespective of the presence of LESCLs. These findings suggest that demographic features not only vary based on CMS or OSMS phenotype, but also with the presence or absence of LESCLs, and that nonetheless, these four phenotypes constitute a continuum.

Background: The diagonal ear-lobe crease (ELC) is reported to be a marker of cardiovascular disease. Very few reports have assessed the relationship of ELC with atherosclerosis. This relationship is investigated here using a Japanese population. Methods and Results: A prospective cross-sectional study included 212 consecutive patients. Bilateral ear lobes were checked for the ELC and this was followed by carotid ultrasonography to measure the far wall common carotid artery intima-media thickness (CCA-IMT), plaque score (PS) and plaque number (PN). Patients with ELC had significantly higher carotid IMT than controls (0.90 ±0.24 vs 0.77 ±0.15, respectively, P

症例は63歳男性運転手，幼少時よりファロー四徴症を指摘されていたが，手術は受けずに観察されていた．突然の意識障害と右片麻痺を発症し当科入院．頭部MRI（拡散強調画像）にて左視床，小脳半球に新鮮梗塞巣を認めた．心臓エコーにて心室中隔欠損，右左シャントを認め，下肢静脈エコーにて両側腓骨静脈に壁在血栓，経頭蓋ドプラでは，脳底動脈に攪拌生理食塩水の末梢静脈投与によりhigh intensity transient signals（HITS）を検出し，奇異性脳塞栓症と考えた．根治手術未施行のファロー四徴症の予後は極めて不良であり，高齢者に初発した脳塞栓症例は本報告が初めてである．慢性低酸素血症に伴う多血症により易血栓性があり，深部静脈血栓症による奇異性脳塞栓再発予防にはワーファリンによる抗凝固療法が必要であると考えた．

Synphilin-1 represents a cytoplasmic protein that interacts with alpha-synuclein and localizes close to synaptic vesicles. The interaction of synphilin-1 with several proteins involved in Parkinson's disease suggests that it might be involved in the pathogenesis of the disease. Nonetheless, the function of synphilin-1 remains unclear. In the present study, we generated transgenic mice expressing human synphilin-1 under the prion protein promoter. Synphilin-1 was widely expressed in neurons in the brain including the substantia nigra, where massive loss of dopamine neurons was not observed. In the transgenic mouse brain, synphilin-1 protein was polyubiquitinated, and partially insoluble. Although modified-SHIRPA revealed no significant difference in behavior and morphology, the reduced rotarod performance and step length were observed in transgenic mice as compared with non-transgenic littermates. Synphilin-1 might be involved in motor function, and its accumulation in the central nervous system can cause motor impairments.

Hypoxia-inducible factor-1alpha (HIF-1alpha) has a central role in neuroprotective responses to hypoxia in the brain. Hydroxylation of HIF-1alpha by prolyl-hydroxylase PHD and aspargynyl-hydroxylase FIH (factor inhibiting HIF-1alpha) causes proteasomal degradation and transcriptional inhibition of HIF-1alpha. Siah ubiquitin ligases regulate the abundance of PHD via targeting for proteasomal degradation. The present study identified Siah-1 as a binding partner for another hydroxylase FIH. Siah-1 and FIH coimmunoprecipitated each other in mammalian cells. Siah-1 was found both to interact with the JmjC domain of FIH through its substrate-binding domain and to specifically ubiquitinate FIH via its RING finger domain. Siah-1 facilitated FIH degradation via the ubiquitin-proteasome pathway under hypoxic conditions. Such findings suggest that Siah ubiquitin ligases might play a role as up-stream regulators of both hydroxylases for HIF-1alpha, i.e., PHD and FIH, by targeting them for proteasomal degradation, leading to increased HIF-1alpha abundance, and transcriptional activity in hypoxia.

Background: No method for the clinical diagnosis of MM2-type sporadic Creutzfeldt-Jakob disease (sCJD) has been established except for pathologic examination. Objective: To identify a reliable marker for the clinical diagnosis of MM2-type sCJD. Methods: CSF, EEG, and neuroimaging studies were performed in eight patients with MM2-type sCJD confirmed by neuropathologic, genetic, and western blot analyses. Results: The eight cases were pathologically classified into the cortical (n = 2), thalamic (n = 5), and combined (corticothalamic) (n = 1) forms. The cortical form was characterized by late-onset, slowly progressive dementia, cortical hyperintensity signals on diffusion-weighted imaging (DWI) of brain, and elevated levels of CSF 14-3-3 protein. The thalamic form showed various neurologic manifestations including dementia, ataxia, and pyramidal and extrapyramidal signs with onset at various ages and relatively long disease duration. Characteristic EEG and MRI abnormalities were almost absent. However, all four patients examined with cerebral blood flow (CBF) study using SPECT showed reduction of the CBF in the thalamus as well as the cerebral cortex. The combined form had features of both the cortical and the thalamic forms, showing cortical hyperintensity signals on DWI and hypometabolism of the thalamus on [18F]2-fluoro-2-deoxy-d-glucose PET. Conclusion: For the clinical diagnosis of MM2-type sporadic Creutzfeldt-Jakob disease, cortical hyperintensity signals on diffusion-weighted MRI are useful for the cortical form and thalamic hypoperfusion or hypometabolism on cerebral blood flow SPECT or [18F]2-fluoro-2-deoxy-d-glucose PET for the thalamic form.

We used electric median nerve stimuli to elucidate the functional properties of neurons in the human secondary somatosensory cortex during exploration of small objects and muscle contraction. Somatosensory evoked fields were recorded from nine healthy subjects with a 204-channel neuromagnetometer. Electrical stimuli were applied once every 3 s to the left median nerve at the wrist. The conditions during the stimulation were rest (control session), exploration of small objects (exploration session) and clenching the hand while the wrist was being electrically stimulated (clench session). The strengths of equivalent current dipoles of evoked fields from the secondary somatosensory cortex were increased during the exploration session, but those of evoked fields were decreased by the clench session.

Objective The clinical trial, Japan Statin Treatment Against Recurrent Stroke (J-STARS), is being carried out to investigate the efficacy of statin treatment against recurrent stroke. To participate in J-STARS, patients must have a past history of ischemic stroke excluding cardioembolic events, and must be clinically diagnosed with hyperlipidemia (HL). Before starting J-STARS, we needed to be aware of the clinical characteristics of the patients who were eligible to participate in this study.Methods Between 1999 and 2002, 7,149 patients with ischemic stroke were enrolled in a stroke data bank developed by the Japan Standard Stroke Registry Study Group. From this, we acquired the data on 1,487 patients with first-ever atherothrombotic infarction (ATI) or lacunar infarction (LI) with a satisfactory functional outcome on discharge.Results Patients with HL were significantly younger (65.3±11.0 vs 68.4±10.9, p

The Japan Statin Treatment Against Recurrent Stroke (J-STARS) Study is a prospective, randomised, open, blinded endpoint study designed to evaluate the effects of pravastatin 10 mg/day in patients who preveously experienced an ischemic stroke other than cardioembolic infarction, but who do not have any CHD requiring statin treatment. We planed to enroll a total of 3, 000 patients. aged 45-80 years who have serum cholesterol level of 180-240 mg/dl. The primary endpoint is fatal and non-fatal stroke recurrence during the follow-up period of 5 year and the data collection phase of the study is expected to be completed by April 2010. Effects of statin on hs-CRP and carotid intima-media thickness will also be investigated as substudies of J-STARS. Further, we planned a longitudinal follow-up study called J-STARS-L (J-STARS-Longitudinal), where we aquired a follow-up data from the stroke data bank developed by the Japan Standard Stroke Registry Study (JSSRS) Group, and attempted to confirm the proposed cardiovascular event rate in the ischemic stroke patients who should be enrolled in J-STARS. The present status of J-STARS-L and J-STARS have been presented in this symposium.

The purpose of the present study was to investigate sequential changes in serum soluble thrombomodulin (sTM) concentrations in patients with acute cerebral infarction (ACI), and to correlate sTM concentrations with the severity of ACI evaluated by Japan Stroke Scale. Eighty-three consecutive patients with ACI were enrolled, and blood examinations were carried out soon after admission and 1 month after. sTM concentrations at admission in patients with cardioembolic infarction (3.2 +/- 1.2 ng/ml) were significantly lower than those of lacunar infarction (3.9 +/- 1.2) (P < 0.05). Serial examinations revealed that sTM concentrations increased significantly 1 month after admission (3.8 +/- 1.2), compared with those at admission (3.6 +/- 1.2) (P = 0.02). Of three ACI subtypes, sTM concentrations during 1 month significantly increased in atherothrombotic infarction (P = 0.002) or, not significantly, in cardioembolic infarction (P = 0.09). The sTM concentrations at admission showed a significant inverse correlation with the severity of ACI (P = 0.04). Although sTM concentrations serve as a useful marker for endothelial cell damage, they are decreased in patients with severe ACI, especially in atherothrombotic and cardioembolic infarctions. Lower sTM concentrations may play some important role in disease progression or in the recurrence following ACI, although the exact mechanism of this unique result should be clarified.

Several studies have demonstrated abnormal MRI findings in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), especially hypertrophy and abnormal enhancement of spinal nerve roots, but there have been few reports on ultrasonographic findings of spinal nerve roots in CIDP. To determine whether ultrasonography (US) enables detection of hypertrophy of the cervical nerve roots, how frequently hypertrophy occurs in CIDP, and whether US findings correlate with any clinical and laboratory features, US of cervical nerve roots was performed using a 7.5-MHz linear-array transducer in 13 CIDP patients and 35 control subjects. A coronal oblique plane with a transducer placed on the lateral side of the neck was used to visualize the cervical nerve roots just after their point of exit from the cervical foramina, and their diameters were measured. US demonstrated hypertrophy of the cervical nerve roots in 9 (69%) of the 13 CIDP patients as compared with findings in control subjects. The degree of hypertrophy was significantly associated with the level of CSF protein (chi2=5.8, p0.05, logistic simple regression analysis) but not with other clinical features. US is considered to be a useful method for evaluating cervical nerve root hypertrophy, which is frequently seen in patients with CIDP, particularly in patients with elevated level of CSF protein.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a slowly progressive or recurrent neuropathy accompanied by infiltration of macrophages in the peripheral nerves. Macrophage colony-stimulating factor (M-CSF) and monocyte chemoattractant protein-1 (MCP-1) are a macrophage-related cytokine and chemokine, respectively. Although, intravenous immunoglobulin (IVIg) infusion therapy has been used for treating CIDP patients, not all CIDP patients have responded to IVIg infusion therapy. To determine the mechanisms of the action of IVIg, we examined serum M-CSF and MCP-1 levels during and after IVIg infusion therapy in 19 CIDP patients treated with IVIg (0.4 g/kg/day for 5 days). Ten of the 19 patients (52.6%) responded to IVIg therapy. Both M-CSF and MCP-1 concentrations in IVIg responders were significantly higher on day 1 postinfusion than those in nonresponders, but decreased to their pretreatment values on day 5 postinfusion. The results suggest that immunomodulation through M-CSF and MCP-1 is involved in the mechanisms underlying the effect of IVIg infusion therapy in CIDP patients.

Background: Folic acid (folate) deficiency causes neurological disorders in aged people, the characteristic features of which were examined. Methods: Serum folate levels were determined in 343 neurological patients by chemiluminescence. We found 36 folate-deficient patients (10.5%) who were divided into elderly ≥ 65 years old (12 cases) and younger group

The progress of a stroke concerns the activation of endothelial cells and platelets. We measured the plasma activities of von Willebrand factor (vWf) and the serum levels of soluble thrombomodulin (sTM) as endothelial markers, and the plasma concentrations of soluble P-selectin (sP-selectin) and soluble E-selectin (sE-selectin) as adhesion molecules during the acute (within 48 h from onset) and subacute (after 1 month from the onset) phases of 52 consecutive patients with acute ischemic stroke and 86 age-matched control subjects. The plasma vWf activities and levels of sP-and sE-selectins in stroke patients were significantly elevated compared with those in controls during both the acute and subacute phases. The serum levels of sTM in stroke patients were significantly higher than those in controls only during the subacute phase. In atherothrombotic infarction, the vWf activities and the levels of sP-selectin, markers for endothelial and platelet activation, remained higher until the subacute phase compared with controls, and the concentrations of sTM, a marker for endothelial injury, were increased during the subacute phase compared with during the acute phase. In lacunar infarction, the levels of sTM and sE-selectin of patients were higher only during the acute phase than controls. These findings suggest that the endothelial cell damage might be maintained until the subacute phase in atherothrombotic infarction, whereas it is remarkable only during the acute phase in lacunar infarction. The evaluation of endothelial markers and adhesion molecules would represent the pathophysiological states of stroke and may provide useful information for the treatment of the ischemic infarction.

Folic acid (folate) levels were measured in the serum of patients with various neurological diseases in Japan. Thirty-six patients showed decreased serum folate levels among 343 consecutive neurological patients (10.5%). Folate administration (15 mg/d) to folate-deficient patients improved neurological symptoms in 24 of 36 cases (67%). Serum folate levels were significantly lower in female than in male folate-deficient patients. Folate-deficient patients showed predominantly axonal neuropathy, which responded to folate supplementation more markedly. Male patients more frequently exhibited neuropathy, especially demyelinating and motor-dominant neuropathy, than females. Anemia was correlated with male sex and low serum folate levels. Male patients were more responsive than females to folate treatment. More male patients had taken excess alcohol or received gastrectomies than females. Neurological symptoms were more frequently improved by folate supplementation in patients with neuropathy than exclusive encephalopathy. Serum folate levels were lower in patients with encephalopathy, especially those with dementia, while folate therapy was more effective in neurological patients without dementia. Dysgeusia and anemia improved in all patients after folate administration. Neurological patients with malabsorption or treated with continuous drip infusion were resistant to folate therapy. Since folate-responsive neuroencepahlopathies are not rare among patients with neurological diseases in Japan, the serum folate level would serve as a valuable indicator for folate supplement therapy.

Immunological abnormality is often found in amyotrophic lateral sclerosis (ALS). Antibodies to sulfoglucuronyl paragloboside (SGPG) were reported in ALS, although the pathogenetic significance of the antibodies is still unknown. We have already demonstrated that SGPG, a unique glycolipid, is present in both peripheral nerve and vascular endothelial cells. To investigate whether serum anti-SGPG antibodies would participate in activation and/or injury of endothelial cells in ALS, we examined serum anti-SGPG antibodies in association with serum soluble E- and P-selectins, which are markers of activated endothelial cells, in 25 patients with ALS and 14 age-matched patients with other neurological diseases (ONDs) using the microtiter-ELISA method. Seven out of 25 ALS patients had anti-SGPG antibodies. Levels of sE-selectin were significantly higher in patients with ALS (48.5 +/- 23.4 ng/ml) compared with ONDs (24.0 +/- 11.8 ng/ml) (P < 0.005). Four out of seven ALS patients with anti-SGPG antibodies had concomitantly high sE-selectin levels. The mean sE-selectin levels were higher in patients with anti-SGPG antibodies (61.9 +/- 25.2 ng/ml) than in those without anti-SGPG antibodies (43.3 +/- 21.1 ng/ml). Anti-SGPG antibodies may take part in the activation and/or injury of endothelial cells. The increased expression of E-selectin may be related to an immunological process in some ALS patients.

In an autopsy case of sporadic rapidly progressive lower motor neuron disease (MND), Gallyas-positive argyrophilic and ubiquitinated filamentous intracytoplasmic inclusions were found in the neurons. Clinically, 7 months prior to death, a 68-year-old woman experienced a history of rapidly progressive muscle weakness of all four extremities and bulbar sign, without sensory and autonomic disturbance. Two months later, she became unable to stand or walk. Four months after onset, she needed respiratory support, and subsequently died due to cardiorespiratory arrest. Neuropathological examinations revealed neuronal loss and associated gliosis in the lower motor neurons, except for ocular motor nuclei, Clark’s column, and accessory cuneate nucleus, and tract degeneration was observed in the middle root zone of the posterior column and spinocerebellar tract. No Bunina bodies or Lewy body-like hyaline inclusions were found in the anterior horns. Gallyas-positive argyrophilic filamentous inclusions were found in the lower motor neurons and in nerve cells of the Clark’s column, intermediate zone, posterior horn and accessory cuneate nucleus. These were positive with anti-ubiquitin antibody but negative with anti-tau (tau-2 and AT8) and neurofilament antibodies. Electron microscopic examinations disclosed randomly arranged tubular-like filamentous profiles, with a diameter of 12–14 nm, sometimes with amorphous granules in the perikaryon. This is the first report on the Gallyas-positive argyrophilic and ubiquitinated filamentous inclusions in neurons in MND.