Thrombolysis for Acute Wake-Up and Unclear-Onset Strokes with Alteplase at 0.6 mg/kg in Clinical Practice: THAWS2 Study.

INTRODUCTION: The aim of this study was to determine the safety and efficacy of intravenous (IV) alteplase at 0.6 mg/kg for patients with acute wake-up or unclear-onset strokes in clinical practice. METHODS: This multicenter observational study enrolled acute ischemic stroke patients with last-known-well time >4.5 h who had mismatch between DWI and FLAIR and were treated with IV alteplase. The safety outcomes were symptomatic intracranial hemorrhage (sICH) after thrombolysis, all-cause deaths, and all adverse events. The efficacy outcomes were favorable outcome defined as an mRS score of 0-1 or recovery to the same mRS score as the premorbid score, complete independence defined as an mRS score of 0-1 at 90 days, and change in NIHSS at 24 h from baseline. RESULTS: Sixty-six patients (35 females; mean age, 74 ± 11 years; premorbid complete independence, 54 [82%]; median NIHSS on admission, 11) were enrolled at 15 hospitals. Two patients (3%) had sICH. Median NIHSS changed from 11 (IQR, 6.75-16.25) at baseline to 5 (3-12.25) at 24 h after alteplase initiation (change, -4.8 ± 8.1). At discharge, 31 patients (47%) had favorable outcome and 29 (44%) had complete independence. None died within 90 days. Twenty-three (35%) also underwent mechanical thrombectomy (no sICH, NIHSS change of -8.5 ± 7.3), of whom 11 (48%) were completely independent at discharge. CONCLUSIONS: In real-world clinical practice, IV alteplase for unclear-onset stroke patients with DWI-FLAIR mismatch provided safe and efficacious outcomes comparable to those in previous trials. Additional mechanical thrombectomy was performed safely in them.

Tumefactive eosinophil-rich non-granulomatous small vessel vasculitis in the cerebrum in a patient with idiopathic hypereosinophilic syndrome.

The definite diagnosis of central nervous system vasculitis requires pathological verification by biopsy or surgical resection of the lesion, which may not always be feasible. A 74-year-old woman with a history of allergic rhinitis, but not asthma, presented with slowly progressive left hemiparesis. Magnetic resonance imaging of the head revealed a heterogeneously enhancing mass involving the right internal capsule and corona radiata. Histological examination of the resected specimen revealed eosinophil-rich non-granulomatous small vessel vasculitis with no neutrophil infiltration or foci of microbial infection. Epstein-Barr virus in situ hybridization was negative, and polymerase chain reaction tests for both T-cell receptor gamma and immunoglobulin heavy-chain variable region genes did not show rearrangements, excluding the possibility of lymphoma and lymphoproliferative disorders. Blood hypereosinophilia and elevated erythrocyte sedimentation rate were observed; however, anti-neutrophil cytoplasmic antibodies were not detected. A biopsy of the erythema in the hips and thighs revealed perivasculitis with eosinophilic infiltration within the dermis. Chest computed tomography revealed multiple small nodules in the lungs. Her symptoms, aside from hemiparesis, disappeared after corticosteroid administration. The clinicopathological features were similar to eosinophilic granulomatosis with polyangiitis but did not meet its current classification criteria and definition. This patient is the first reported case of idiopathic eosinophilic vasculitis or idiopathic hypereosinophilic syndrome-associated vasculitis affecting the small vessels in the brain. Further clinicopathological studies enrolling similar cases are necessary to establish the disease concept and unravel the underlying pathogenesis.

Association between Serum Uric Acid Level and Activity of Daily Living in Japanese Patients with Ischemic Stroke.

BACKGROUND: An association between serum uric acid and outcomes of ischemic stroke has been reported, but the results are controversial. The aim of this study is to clarify how uric acid may affect activities of daily living after acute ischemic stroke. METHODS: Consecutive Japanese patients with acute ischemic stroke were analyzed. Serum uric acid quartiles and activities of daily living at hospitalization and discharge in men and women were examined. Activities of daily living were evaluated using the modified Rankin scale score, and a score of 3 or higher was defined as poor activities of daily living. P values less than .05 were considered significant. RESULTS: A total of 987 patients with acute ischemic stroke (591 men; mean age, 72.3 years) were analyzed in this study. We observed a U-shaped relationship between serum uric acid and poor activities of daily living in both men and women at hospitalization and discharge. Multivariate analysis demonstrated that the first quartile group of serum uric acid was significantly associated with poor activities of daily living in both men and women, using the third quartile group as the reference. CONCLUSIONS: Lower serum uric acid can be a marker for predicting poor activities of daily living in patients with acute ischemic stroke, irrespective of sex.

Association between body mass index and outcome in Japanese ischemic stroke patients.

AIM: An association between body mass index (BMI) and stroke outcome have been reported, but the results are controversial. The aim of the present study was to evaluate whether BMI is associated with ischemic stroke outcome. METHODS: Consecutive Japanese acute ischemic stroke patients were analyzed. BMI was categorized as underweight (BMI <18.5 kg/m2 ), normal weight (18.5-24.9 kg/m2 ) and obese (≥25 kg/m2 ). BMI and short-term and long-term outcomes were examined. Short-term outcomes were evaluated using the modified Rankin scale score at hospitalization and discharge; modified Rankin scale ≥3 was defined as a poor outcome. Long-term outcomes were evaluated by all-cause mortality. The recurrence rate was also evaluated in each BMI group. Values of P < 0.05 were considered significant. RESULTS: A total of 1206 acute ischemic stroke patients (760 men; mean age 72.5 years) were analyzed in the present study. There were 111 underweight cases (9.2%), 785 normal weight cases (65.1%) and 310 obese cases (25.7%). The underweight group had a significantly higher rate of poor short and long-term outcomes than the normal weight group. The outcomes of the obese group were not significantly different from those of the normal weight group. Recurrence was not significantly different among the groups. CONCLUSIONS: Lower BMI might be a predictor of poorer short-term and long-term stroke outcomes. Geriatr Gerontol Int 2017; 17: 369-374.

Plasma Brain Natriuretic Peptide is a Marker of Prognostic Functional Outcome in Non-Cardioembolic Infarction.

BACKGROUND: High plasma levels of brain natriuretic peptide (BNP) may also be observed in patients with non-cardioembolic infarction (CEI). We aimed to evaluate the relation between plasma BNP level, clinical parameters, and functional outcome in patients with and without CEI. METHOD: This study analyzed consecutive Japanese patients with acute ischemic stroke. Correlations between plasma BNP level and conventional risk factors for ischemic stroke were examined. Values of P less than .05 were considered statistically significant. RESULTS: This study analyzed 718 acute ischemic stroke patients (445 men and 273 women; mean age, 73.9 years). Mean plasma level of BNP was significantly higher for CEI (366.6 pg/ml) than for non-CEI (105.6 pg/ml; P < .01). Poor outcome (modified Rankin Scale score ≥3) at hospitalization and discharge were associated with significantly higher plasma BNP level than good outcome (modified Rankin Scale score ≤2) for both CEI and non-CEI. On multiple regression analysis, log-BNP was significantly associated with female sex, smoking, triglyceride, and creatinine clearance in CEI. In non-CEI, log-BNP was significantly associated with systolic/diastolic blood pressure, triglyceride, high-density lipoprotein cholesterol, and creatinine clearance. CONCLUSION: Irrespective of the presence of CEI, plasma BNP offers a marker of prognostic functional outcome. We clarified the characteristics and differences associated with plasma BNP in CEI and non-CEI, and our results suggest that plasma BNP can provide a useful marker of brain damage and neurohumoral dynamics in acute ischemic stroke.

Validity of the Japanese version of the REM Sleep Behavior Disorder (RBD) Screening Questionnaire for detecting probable RBD in the general population.

AIMS: In order to evaluate the validity of the REM Sleep Behavior Disorder (RBD) Screening Questionnaire (RBDSQ) as a screening tool for RBD in a general population setting, we conducted a validation study using residents of a rural community. METHODS: We sent questionnaires that included the RBDSQ to 2631 eligible adult residents in the town of Daisen, Japan. RESULTS: Of those residents, 1572 participants (59.7%) gave complete answers to the RBDSQ. Among them, 179 participants (11.4%) scored ≥5 points on the questionnaire; an additional 149 participants scoring ≤4 points were randomly selected for further telephone interview. Based on obtained results, nine participants (0.57%) were judged as having probable RBD. Receiver-operator curve analysis revealed that a total score of 6 points on the RBDSQ represented the best cut-off value for detecting probable RBD (sensitivity: 100%; specificity: 73.0%). Analysis based on the item response theory revealed that items 1, 4, 6-1, 7, and 8 had lower difficulty than the remaining items, suggesting that these items are more essential in the screening for probable RBD. CONCLUSIONS: The present study revealed that a score of 6 points on the RBDSQ could be used as a cut-off value for the screening of probable RBD in the general population. Evaluation of the distribution of positive items might be helpful for identifying the intensity of a person's RBD symptoms.

A two-year follow-up study on the symptoms of sleep disturbances/insomnia and their effects on daytime functioning.

OBJECTIVE: This study attempts to identify changes in the symptoms of sleep disturbances/insomnia over a two-year course and their effects on daytime functioning. METHODS: We administered two population-based epidemiological surveys in 2005 and 2007 to participants from rural Japan. RESULTS: In the first survey, 30.7% of the subjects reported sleep disturbances/insomnia. Among them, 60.9% reported sleep problems at the two-year follow-up. A comparison of sleep disturbances/insomnia, and subjective daytime functioning measures between the new incident cases and persistent poor sleepers revealed that the total score of persistent poor sleepers was significantly lower than that of new incident cases on the Pittsburgh Sleep Quality Index and physical quality of life (QoL) but not mental QoL. Longitudinal comparisons of the symptoms of sleep disturbances/insomnia in persistent poor sleepers revealed that sleep efficiency was significantly worse at follow-up. Exacerbation of the symptoms of sleep disturbances/insomnia at follow-up was observed in mild but not severe cases. CONCLUSIONS: Sleep efficiency progressively worsens over time, and physical QoL can deteriorate as sleep disturbances/insomnia become chronic. Since the symptoms of sleep disturbances/insomnia and their daytime effects are exacerbated even in mild cases, early intervention and treatment are necessary.

Epidemiological survey of frontotemporal lobar degeneration in tottori prefecture, Japan.

BACKGROUND: The prevalence of frontotemporal lobar degeneration (FTLD) in Japan is unknown. An epidemiological survey study of FTLD was undertaken in Tottori Prefecture, a district in the western region of Japan. METHODS: Hospitals in Tottori Prefecture were surveyed by a two-step questionnaire in 2010, and the prevalence of FTLD per 100,000 inhabitants was calculated using the actual number of patients and inhabitants in Tottori Prefecture on the prevalence day of October 1, 2010. RESULTS: In this survey, 66 patients were diagnosed with FTLD. The subtypes of FTLD were as follows: 62 cases of frontotemporal dementia (FTD), 3 cases of progressive nonfluent aphasia, and 1 case of semantic dementia. Among the FTD cases, 5 cases were FTD with motor neuron disease and 1 case was FTD with parkinsonism linked to chromosome 17. The prevalence of FTD in the total population of Tottori Prefecture was 11.2 per 100,000 inhabitants. Based on these results, the prevalence of FTLD in Japan in 2008 was estimated to be 9.5 per 100,000 individuals. CONCLUSIONS: Our epidemiological survey results suggest that there are at least 12,000 FTLD patients in Japan, indicating that FTLD is not a rare disease.

Prospective survey on the natural course of restless legs syndrome over two years in a closed cohort.

OBJECTIVE: This study was set out to identify the population with restless legs syndrome (RLS) developing a chronic course and the impact of long-term morbidity of RLS on disorder related dysfunctions. METHODS: Two population-based epidemiological surveys were performed in 2005 and 2007 on the same cohort in Japan. Questionnaires including demographics, measurement scales for depression, quality of life, subjective sleep disturbances, and the NIH/IRLSSG consensus questionnaire for RLS diagnosis, were distributed to participants, and then telephone interviews were performed to determine the diagnosis and severity of RLS. RESULTS: Among 1592 valid respondents, only 20 (40%) of 50 RLS-positive subjects at the first survey were repeatedly RLS-positive at the second survey. The frequency of RLS symptoms at the first survey was associated with the repeated appearance of RLS symptoms (odds ratio 8.70, p=0.0302). The chronic morbidity of RLS seemed to be associated with the existence of depression and subjective sleep disturbance. CONCLUSIONS: RLS may not be persistent in more than 50% of the affected population. The frequency of RLS symptoms, but not the severity, may predict the persistence of this disorder.

Correlations among insomnia symptoms, sleep medication use and depressive symptoms.

AIM: To elucidate the factors associated with insomnia symptoms and the use of sleep medication, and the correlations among insomnia symptoms, sleep medication use and depressive symptoms in the general population. METHODS: This survey was conducted in a rural community of Japan. Questionnaires consisted of basic information, the Pittsburgh Sleep Quality Index, and a 12-item version of the Center for Epidemiological Studies Depression scale, and were administered to all community members aged 20 years or over. A total of 2822 respondents with valid answers were subjected to analysis. RESULTS: Occurrence of insomnia symptoms appeared to be associated with advancing age and existence of depressive symptoms. The extent of sleep medication use in the entire sample was 9%, and the value in the subjects with insomnia symptoms was 26%. Sleep medication use in insomniacs was associated with female sex and advancing age as well as higher scores in subcomponents of both poor subjective sleep quality and prolonged delay of sleep onset. Depressive symptoms were worst in the group with insomnia symptoms using sleep medication, and were significantly lower in the group without insomnia symptoms using sleep medication. CONCLUSIONS: Our study revealed that female sex, advancing age, depressive symptoms, poor sleep quality, and prolonged delay of sleep onset appeared as risk factors for sleep medication use. Insomnia symptoms were suspected to act as an exacerbating factor for depressive symptoms. However, our findings suggested that appropriate use of sleep medication could reduce depressive symptoms in the subjects with insomnia symptoms.

Long-term prognosis of patients with large subcortical infarctions.

AIM: We assessed the long-term prognosis of patients with large subcortical infarctions (LSCI). METHODS: We defined LSCI as lesions > or =15 mm confined to deep penetrating arteries without a cardioembolic or atherothrombotic source. Patients with acute ischemic strokes were consecutively registered and followed for 751 +/- 441 days. The clinical characteristics and long-term prognoses of patients with LSCI were compared to those of patients with lacunar (LACI), atherothrombotic (ATI) and cardioembolic infarctions (CEI). RESULTS: At discharge from the hospital, the proportion of good outcomes (modified Rankin Scale < or =2) for patients with LSCI (52.1%) was similar to that for ATIs (47.2%), but worse than that for LACIs (73.2%). After a 3-year follow-up period, the mortality rates from LSCI, LACIs, ATIs and CEIs were 8.4, 8.2, 22.3 and 41.1%, respectively; the recurrence rates were 9.3, 14.1, 16.6 and 23.8%, respectively. CONCLUSIONS: The short-term prognosis of functional outcomes for LSCI was worse than that for LACIs, but similar to acute-phase ATI outcomes. The long-term prognosis after a LSCI is good, and recurrence tends to be lower than for LACIs.

Changes in prevalence and incidence of Parkinson's disease in Japan during a quarter of a century.

BACKGROUND/AIM: To determine the prevalence and incidence of Parkinson's disease (PD) and compare them with results from our previous studies. METHODS: We examined epidemiological characteristics of PD patients using a service-based study in Yonago City, and a door-to-door study in Daisen Town. The prevalence days were April 1, 2004 in Yonago, and April 1, 2003 in Daisen. RESULTS: In Yonago, we identified 254 PD patients. The crude prevalence was 180.3 (95% CI, 158.1-202.4) per 100,000 population. The adjusted prevalence was 145.8 (95% CI, 145.2-146.5) in 1980, 147.0 (95% CI, 146.3-147.6) in 1992, and 166.8 (95% CI, 166.1-167.5) in 2004, when calculated using the Japanese population in 2004. The crude incidence was 18.4 (95% CI, 11.3-25.5) per 100,000 population per year. The crude incidence in 1980 was 10.2 (95% CI, 4.6-15.8), and the adjusted incidence was 9.8 (95% CI, 4.3-15.3) in 1992, and 10.3 (95% CI, 4.7-15.9) in 2004, when calculated using the population in Yonago in 1980. In Daisen, there were 21 PD patients. The crude prevalence was 306.6 (95% CI, 175.7-437.6) and the adjusted prevalence was 192.6 (95% CI, 191.9-193.8). CONCLUSIONS: The prevalence of PD had increased, primarily because the population had aged. Differences in prevalence between these adjacent areas may have resulted from differences in the methods of investigation.

Prevalence of restless legs syndrome in a rural community in Japan.

To assess the prevalence and clinical significance of restless legs syndrome (RLS) in a Japanese population, we carried out a community-based survey in a rural area of Japan. We sent questionnaires requesting information on demographics, the Center for Epidemiological Studies Depression scale, the Short Form-8, the Pittsburgh Sleep Quality Index, the National Institutes of Health/International RLS Study Group (IRLSSG) consensus questionnaire, and the IRLSSG severity scale for RLS (IRLS) to 5,528 eligible adult residents in the town of Daisen in the Tottori prefecture of Japan. Next, we performed telephone interviews to identify subjects with probable RLS. Of the 2,812 subjects (51.1%) who gave complete answers on the IRLSSG questionnaire, 50 (1.8%) were judged as RLS positive. The prevalence of RLS was significantly higher in women than in men, and significantly lower in individuals 60 years of age or older. Multiple logistic regression analysis revealed that the existence of RLS was significantly associated with depression, lowered mental quality of life, and sleep disturbances. The prevalence of RLS in adult Japanese populations may be lower than that reported in Caucasian populations. However, in a group of Japanese subjects, RLS had a significant impact on daytime functioning as well as subjective sleep quality.

CSF orexin levels of Parkinson's disease, dementia with Lewy bodies, progressive supranuclear palsy and corticobasal degeneration.

Excessive daytime sleepiness has been widely accepted as a common problem not only in Parkinson's disease (PD) but also in other related disorders. Lowered excretion of orexin A (hypocretin 1) into the cerebrospinal fluid (CSF) is known to play a pathological role in narcolepsy and secondary hypersomnia due to hypothalamic dysfunction. Although the levels of CSF orexin in PD have been previously examined, the results have been controversial, and no systematic investigation of CSF orexin excretion has been conducted on PD related disorders. In this study, orexin was measured in CSF collected by lumbar puncture in 62 patients with PD, 13 patients with dementia with Lewy bodies (DLB), 16 patients with progressive supranuclear palsy (PSP), and 7 patients with corticobasal degeneration (CBD). Levels of CSF orexin (mean+/-SD pg/ml) were 302+/-38 in PD, 297+/-48 in DLB, 258+/-37 in PSP, 246+/-90 in CBD. The occurrence of low orexin levels (

Epidemiology of primary focal dystonias in the western area of Tottori prefecture in Japan: Comparison with prevalence evaluated in 1993.

An epidemiological survey of primary focal dystonias in the western area of Tottori Prefecture in Japan was conducted in 2003, and the results were compared with those of a previous survey in 1993. The service-based prevalence of primary focal dystonia was 13.7 per 100,000 population, representing an increase from that found in the 1993 survey. In 1997, botulinum toxin type A was approved for use in Japan to treat blepharospasm, and the increased number of patients now being evaluated and diagnosed with focal dystonias at medical centers throughout Japan may be responsible for this increased prevalence. Prevalence by subtype per 100,000 population was as follows: facial dystonia, 6.5; spasmodic torticollis, 2.0; writer's cramp, 4.4; and other focal dystonias; 0.8. Facial dystonia showed the most marked increase in service-based prevalence among these subtypes.

[Anti-Yo antibody associated paraneoplastic cerebellar degeneration with gastric adenocarcinoma in a male patient: a case report].

We report a 71-year-old man presenting with paraneoplastic cerebellar degeneration (PCD) associated anti-Yo antibody after surgery for gastric adenocarcinoma. Seven months after partial gastrectomy, he deviated to the right on walking. Furthermore, a feeling of dysarthria appeared and he was unable to sit after 2 months. When he was hospitalized, he showed a disturbance of his eye movement on lower gaze, a nystagmus on lateral gaze, saccadic eye movement on smooth pursuit, cerebellar ataxia, and decreasing of muscle tonus in his extremities. However, no atrophic findings of the brainstem and cerebellum were revealed by brain MRI. He responded poorly to treatment with high-dose methylprednisolone, high-dose immunoglobulin, double filtration plasmapheresis and rehabilitation. There was a strong anti-Yo immunohistochemical staining of the cytoplasm in both the patient's tumor cells and normal cerebellar Purkinje cells. These findings suggest that PCD associated with anti-Yo antibody triggered by adenocarcinoma might occur in this male patient.

Increased plasma transforming growth factor-beta1 in migraine.

BACKGROUND AND OBJECTIVES: Migraine is characterized by the peripheral and central sensitization of pain perceptive neural systems, and neurogenic inflammation is a key step in the development of migraine headache. We focused on transforming growth factor-beta1 (TGF-beta1), which is a multifunctional proinflammatory cytokine. To address the possibility of TGF-beta1 involvement in migraine, we investigated the plasma level of TGF-beta1 in patients with migraine headache during headache-free periods. SUBJECTS AND METHODS: Sixty-eight subjects with migraine participated: 23 with migraine with aura (MWA) and 45 without aura (MWoA). We recruited 58 healthy subjects without headache as controls. In addition, we examined 12 subjects with episodic tension-type headache. Platelet poor plasma (PPP) was obtained from subjects during headache free-periods. TGF-beta1 levels in PPP were determined by enzyme-linked immunosorbent assay. RESULTS: The TGF-beta1 level in PPP was 2.62*+/- 0.23 (mean +/- SE) ng/mL in migraine, 2.08 +/- 0.20 ng/mL in tension-type headache, and 1.80 +/- 0.09 ng/mL in controls (P= .007, ANOVA; *P < .01, post hoc tests vs. the controls). CONCLUSION: TGF-beta1 in PPP was significantly increased in patients with migraine during headache-free periods. TGF-beta1 may play some role in the development of migraine headache.

Association of the insertion/deletion polymorphism of the angiotensin I-converting enzyme gene in patients of migraine with aura.

Recently, several angiotensin I-converting enzyme (ACE) inhibitors and an angiotensin II receptor blocker were demonstrated to have a clinically important prophylactic effect in migraine. ACE is one of the key enzymes in the rennin-angiotensin-aldosterone system, which modulates vascular tension and blood pressure. In humans, serum ACE levels are strongly genetically determined. Individuals who were homozygous for the deletion (D) allele showed increased ACE activity levels. To investigate the role of ACE polymorphism in headache, we analyzed the ACE insertion (I)/deletion (D) genotypes of 54 patients suffering from migraine with aura (MwA), 122 from migraine without aura, 78 from tension-type headache (TH), and 248 non-headache healthy controls. The ACE D allele were significantly more frequent in the MwA than controls (p<0.01). The incidence of the D/D genotype in MwA (25.9%) was significantly higher than that in controls (12.5%; p<0.01; odds ratio=5.26, 95% confidence interval: 1.69-16.34, adjusted for age and gender). No differences in the remaining groups were found. Our results support the conclusion that the D allele and the D/D genotype in the ACE gene is a genetic risk factor for Japanese MwA. There seems to be a possible relationship between ACE activity and the pathogenesis of migraine.

Stroke recurrence within the first year following cerebral infarction--Tottori University Lacunar Infarction Prognosis Study (TULIPS).

OBJECTIVES: To identify determinants of recurrence after ischemic stroke in the Japanese population. MATERIALS AND METHODS: We enrolled 885 patients with acute ischemic stroke that had been admitted to our community hospitals. A total of 831 cases were followed for 1 year after the index stroke. Patients were assigned to one of the ischemic stroke subtype groups based on the NINDS Stroke Data Bank criteria. RESULTS: Rates of stroke recurrence were significantly different among stroke subtype groups: 14.4% in cardioembolic infarction, 7.3% in atherothrombotic infarction (ATI), 6.2% in lacunar infarction (LI) and 7.8% in infarction of uncertain cause. Previous history of stroke was the predictor of stroke recurrence for the groups of ATI and LI patients, and diabetes mellitus was the predictor of recurrence for the group of LI patients. CONCLUSION: The rate of recurrence and risk factors for stroke recurrence are different by stroke subtypes.