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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.

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.

The efficacy of reperfusion therapy (RT) using intravenous infusion of recombinant tissue plasminogen activator and/or endovascular therapy for minor ischemic stroke (MIS) has not yet been established. The present study aimed to elucidate the clinical features of MIS patients with atrial fibrillation (AF) and examine whether they could be potential candidates for RT. Data of MIS patients, defined as those with a score ≤ 5 on the National Institute of Health Stroke Scale, were extracted from patients admitted to our hospital between 2006 and 2018, and clinical characteristics were compared between the AF and non-AF groups. Thereafter, the impact of RT on outcomes in the AF- group was evaluated using the modified Rankin scale (mRS) score 3 months after onset and compared to that of standard medical therapy (SMT) using propensity score matching (PSM). Of 10,483 stroke patients, 3003 were shortlisted, and 457 AF patients and 2546 non-AF patients were finally selected. Patients in the AF group had more RT (13.3% vs. 5.7%, p

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.

A 75-year-old man having dementia and lifestyle related diseases developed a lobar intracerebral hemorrhage (LICH) in the left parietal and a small cerebellar infarction in the left occipital lobe. Many micro bleeds (MB) due to cerebral amyloid angiopathy (CAA) in the subcortical areas and multiple vascular stenosis were also found by MRI and MRA. He developed herpes zoster in his buttocks on day 6 of hospitalization and complicated with varicella zoster virus (VZV) meningitis with positive for VZV-DNA in the cerebrospinal fluid. Subsequently, LICHs occurred in the left frontal lobe and in the right parietal lobe for a short period of time and died on the day 18. We speculated that the repeating hemorrhages was primarily caused by VZV vasculopathy and additionally the subcortical MBs increased the hemorrhagic risk. The relationship between VZV vasculopathy and CAA should be studied in the future.

We treated 437 cases of adult aseptic meningitis and 12 cases (including 2 recurrent patients; age, 31.8 ± 8.9 years; 7 females) of herpes simplex meningitis from 2004 to 2016. The incidence rate of adult herpes simplex meningitis in the cases with aseptic meningitis was 2.7%. One patient was admitted during treatment of genital herpes, but no association was observed between genital herpes and herpes simplex meningitis in the other cases. The diagnoses were confirmed in all cases as the cerebrospinal fluid (CSF) was positive for herpes simplex virus (HSV)-DNA. For diagnosis confirmation, the DNA test was useful after 2-7 days following initial disease onset. Among other types of aseptic meningitis, the patients with herpes simplex meningitis showed relatively high white blood cell counts and relatively high CSF protein and high CSF cell counts. CSF cells showed mononuclear cell dominance from the initial stage of the disease. During same period, we also experienced 12 cases of herpes simplex encephalitis and 21 cases of non-hepatic acute limbic encephalitis. Notably, the patients with herpes simplex meningitis were younger and their CSF protein and cells counts were higher than those of the patients with herpes simplex encephalitis.

This study reports eleven cases of reversible cerebral vasospasm syndrome (RCVS). Of the 11 patients, two were males and nine were females, with the average age of 47.9 ± 14.1 years. Many of these patients were young. The rates of severe, intractable and pulsative headache, generalized convulsions, and motor hemiparesis were 64%, 27%, and 36%, respectively. As complications of intracerebral lesions in the early stage of disease onset, convexal subarachnoid hemorrhage, lobar intracerebral hemorrhage, and posterior reversible encephalopathy syndrome were observed in 63%, 9%, and 45% of cases, respectively. Cerebral infarction occurred in 45% of cases at around 1-3 weeks after onset. Improvement of cerebral vasoconstriction was recognized in several cases from about the first month of onset. The post-partum period, migraine, transfusion, rapid amelioration for anemia, renal failure, bathing, and cerebrovascular dissection were suspected as disease triggers. Abnormally high blood pressure at onset was confirmed in 55% of cases. It is important to analyze the pathophysiology of RCVS associated with these triggers from the viewpoint of the breakdown of the blood-brain barrier.

Background The etiology of transient global amnesia (TGA) remains unclear. We studied the pathophysiology of TGA in 165 Japanese patients. Subjects and Methods TGA was diagnosed in hospitalized patients from 2004 to 2015. We analyzed clinical characteristics, magnetic resonance imaging findings, and maximum intima-media thickness of the common carotid artery, and the reflux of internal jugular venous (IJV) flow by ultrasonography, and statistically compared patients with TGA with age-matched and sex-matched patients who have had a transient ischemic attack (TIA), small-vessel occlusion (SVO), and normal controls (each group, N = 165). Results Patients with TGA showed lower prevalence of vascular risk factors than patients with TIA and SVO did. Eleven patients (6.7%) had 2 episodes of TAG, but specific clinical variables could not be recognized in these patients. The maximum intima-media thickness was significantly thinner in TGA (1.1 ± .7 mm) than in SVO (1.6 ± .9 mm; P = .001). The percentages of cases whose IJV flow reflux was increased by Valsalva maneuver showed no difference ( P = .573) between TGA (26.0 %) and SVO (29.4%). MR diffusion-weighted imaging yielded small hyperintense signals in the hippocampus in 64 of 90 (71.1%) patients between 24 and 72 hours. Potential precipitating specific factors or events before the attacks could be recognized in 40 cases (24.2%) of 165 patients. Conclusion Arterial ischemia and IJV flow reflux might not contribute to TGA pathophysiology. The vulnerability of the hippocampus to physical or emotional stress might be suspected as an underlying mechanism in some patients with TGA.

We report two cases (a married couple) of intoxication due to angel's trumpet ingestion. Case 1: A 71-year-old woman was found lying unconscious on the sofa at home and was brought to our hospital by ambulance. She showed mydriatic anisocoria, and an intracerebral lesion was suspected. However, the brain magnetic resonance imaging showed no abnormal lesion and acute encephalopathy of unknown cause was diagnosed. Case 2: A 68-year-old man (husband of the patient of Case 1) showed alteration of consciousness with agitation and was admitted to our hospital on the next day. He also had slight mydriasis. As his manifestations were similar to those of his wife, we studied their medical history again. We found that they mistook the roots of angel's trumpet for burdock and cooked and ate them. This intoxication causes characteristic encephalopathy with altered consciousness and mydriasis. In the case of anisocoria or mild mydriasis, the diagnosis is difficult sometimes. The intoxication occurred within a family; this was a clue to the correct diagnosis. Severe cases exhibit pyramidal signs and symptoms or convulsion, and deaths have been reported. Angel's trumpet intoxication is an important neurological emergency.

Purposes: The efficacy of reperfusion therapies (RT), including both intravenous recombinant tissue plasminogen activator (iv rt-PA) and any endovascular therapy (EVT) for mild acute ischemic stroke (AIS), is yet to be established. The present study aimed to evaluate the impact of RT on mild AIS patients outcome compared with non-RT. Methods: Of all 9775 AIS patients admitted in our hospital between 2006 and 2017, those patients with values of 0-1 on the modified Rankin Scale (mRS) prior to the onset of AIS and of ≤ 10 on the National Institute of Health Stroke Scale (NIHSS) just before the therapy was started were selected. Of these, RT patients and comparable non-RT patients were selected using propensity score matching. The RT group included patients with iv rt-PA and any EVT (local arterial infusion of Urokinase, percutaneous transluminal angioplasty, Merci retriever, Penumbra system, and any stent retriever). The primary outcome was mRS 0-1 at three months after the onset, which was defined as an excellent outcome. Subgroup analysis for patients with NIHSS ≤ 5, 6-10, small vessel occlusion (SVO), and non-SVO was also performed. Results: Of the selected 3089 patients, we constructed the 526 (263 each) propensity score-matched patients cohort. The propensity score-matched RT patients consisted of 135 solely iv rt-PA, 109 EVT, and 19 both. The non-RT patients had a median age of 72 compared to 73 years for the RT patients and the median NIHSS was 5 in both patient groups. The frequencies of excellent outcome in RT and non-RT patients did not differ significantly with 57.8 % and 52.1 %, respectively. The odds ratio and 95 % confidence interval (CI) of RT patients for an excellent outcome was 1.26 (0.89-1.78). In the subgroup analysis, odds ratios of patients with NIHSS ≤ 5, NIHSS 6-10, SVO, and non-SVO were 0.97 (0.61-1.56), 1.75 (1.01-3.03), 1.24 (0.57-2.70), and 1.27 (0.86-1.86), respectively. Conclusion: The present study found an excellent outcome of RT only in patients with NIHSS 6-10. Further studies may be warranted to investigate the efficacy of RT for patients with mildest AIS (NIHSS ≤ 5).

This study aimed to determine the risk factors for recurrent post stroke seizure (PSS) and the efficacy of anti-epileptic drugs (AED) in patients having intracerebral hemorrhage (ICH) with initial seizure.A total of 1920 consecutive patients with ICH from 2004 to 2012 were investigated retrospectively. The relationships among the baseline clinical and radiological data, administration of AED, and incidence of initial and recurrent PSS were evaluated using multiple logistic regression analysis.Seizures occurred in 127 (6.6%) of the 1920 patients, displaying statistically significant relationships with cortical involvement of a cerebral lesion (P0.001), non-hypertensive ICH (P0.001), younger age (P0.001), and severe neurological deficits (P0.001). Early (4.3%) and late seizure (2.3%) had no significant relationship with the development of recurrent PSS. Larger volume of hematoma was the only independent factor associated with recurrence of PSS (OR 1.03; 95% CI 1.00-1.05; P=0.027). A Kaplan Meier survival analysis revealed that AED treatment had a poor association with recurrence of PSS (P=0.750).Larger volume of hematoma was predictive of recurrence of PSS. AED therapy had poor association with preventing the recurrence of PSS.

Objective The effects of large-volume epidural blood patch (EBP) remain unclear in patients with cerebrospinal fluid (CSF) leak. We report excellent outcomes from 15 consecutive CSF leak cases that underwent a large-volume EBP using an intravenous catheter from a single lumbar entry point, together with outcomes from 4 patients who underwent direct surgical closure or drip-and-rest therapy during the same period. Methods Nineteen patients with idiopathic CSF leaks were enrolled in this study since November 2011 (12 women; mean age, 43.3 ± 14.0 years). Patient demographic data, radiologic findings, symptoms, administrated therapies, complications, and clinical courses were investigated retrospectively. Results Different types of headache were observed, including typical orthostatic headache alone (n = 10), orthostatic headache with chronic subdural hematoma (CSDH) (n = 3), and posture-unrelated headache accompanied with CSDH (n = 6). Regarding treatments, in 1 case, direct surgical closure was performed. In 15 cases, large-volume EBPs were performed, and the volume of injected blood was 44.8 ± 21.6 mL. The other 3 cases were treated by simple drip infusion regardless of the drainage for CSDH. Out of 9 cases with accompanied CSDH, recurrence of subdural hematoma was completely prevented by the application of an EBP after drainage in 5 cases and without drainage in 3 cases, and by simple intravenous drip-and-rest therapy after drainage in 1 case. Among 10 patients suffering from typical orthostatic headache alone, symptoms disappeared completely in 7 cases and were relieved in 3 cases. Conclusions We demonstrate here a perfect control of spinal CSF leaks with the administration of a large-volume EBP through an intravenous catheter.

A 50-year-old woman was admitted to our hospital with dysesthesia on the right upper portion of her face and a headache. Diffusion-weighted brain magnetic resonance imaging (MRI) revealed high-intensity signals in the dorsolateral portion of the medulla oblongata. She was diagnosed with lateral medullary infarction and was intravenously treated with sodium ozagrel. On the second day of hospitalization, she had nausea and vomiting and showed nystagmus to all directions, suggesting damage to the vestibular nucleus. These manifestations coincided with partial symptoms of lateral medullary syndrome. On the third day of hospitalization, a rash appeared on the region of skin innervated by the first and second branches of the right trigeminal nerve. A reevaluation of the MRI findings indicated the presence of a lesion of the right spinal trigeminal nucleus and tract. She was treated with acyclovir for 14 days, and was discharged without any residual symptoms. Varicella zoster virus-DNA was detected in her cerebrospinal fluid. This disease mimics the presentation of a stroke and is important for differential diagnosis. (Received August 1, 2017; Accepted September 14, 2017; Published February 1, 2018).

Background and Purpose: It has not fully investigated whether the benefit from revascularization therapy for patients with mild acute ischemic stroke (AIS) can overweigh the risk. The aim of this study was to investigate the impact of revascularization therapy on patient outcome as related to the severity of the stroke. Methods: From our hospital’s stroke database from January 2006 to March 2017, we extracted data for patients with AIS. Eligible criteria for the patients were: modified Rankin Scale (mRS) of 0 or 1 before onset, admitted less than 24 hours after onset, and followed up for at least 3 months. Revascularization therapy included intravenous tissue plasminogen activator; endovascular therapy (intra-arterial urokinase infusion, percutaneous transluminal angioplasty, emergent carotid artery stenting, and thrombectomy); and carotid endarterectomy performed within 14 days from onset. Patients were divided into 4 groups based on the severity using the National Institutes of Health Stroke Scale (NIHSS) on admission : Group 1 = 0-4, Group 2 = 5-9, Group 3 = 10-19, and Group 4=20-. We defined a good outcome as mRS score of 0-1 at 3 months after onset. The odds ratio of a good outcome was computed among 4 groups, adjusting for age and sex. Results: We extracted data for 3275 patients with AIS (71.3 years, 65.1% men). Of these, 17.9% received revascularization therapy of any type. This was distributed across the 4 NIHSS groups as follows: 6.1% of Group 1 (n=2193), 27.1% of Group 2 (n=527), 56.4% of Group 3 (n=298), and 55.6% of Group 4 (n=257). The odds ratios (95% confidence interval) of treatment for good outcome in group 1 to 4 were 0.42 (0.29-0.62), 1.15 (0.78-1.72), 2.80 (1.60-4.90), and 4.40 (1.79-10.82), respectively. Group 1 was further divided into 5 subgroups by each NIHSS scores of 0-4. The odds ratios for each subgroup (NIHSS scores 0, 1, 2, 3, and 4) were 0.20 (0.07-0.61), 0.28 (0.11-0.69), 0.27 (0.11-0.69), 0.93 (0.43-2.03), and 0.88 (0.42-1.85), respectively. Conclusions: Approximately half of the patients with NIHSS score of ≥10 received revascularization therapy and had significant benefit. However, revascularization therapy for patients with mild AIS (specifically NIHSS scores of 0, 1, or 2) could be rather harmful.

We experienced 13 cases (29.8 ± 7.0 years) of mumps meningitis and 365 cases of adult aseptic meningitis during 11 years from 2004 to 2014. A small epidemic of mumps occurred for 3-4 years, and the incidence rate of adult mumps meningitis coincided with the epidemic without seasonal fluctuation. Parotitis was observed in 8 of the 13 mumps meningitis patients (61.5%) and orchitis in 2 of 7 male patients (28.6%). There were no differences in clinical manifestations, laboratory findings, and outcome between patients with adult mumps meningitis and those with echovirus 9 meningitis (9 patients), except for the low frequency of nausea/vomiting and a high percentage of mononuclear cells of the cerebrospinal fluid in those with mumps. Eight patients had contact with persons with mumps before the symptomatic stage of meningitis. Only one patient had received mumps vaccination in childhood. On the basis of the values of the anti-mumps IgM and IgG antibodies, we speculated primary infection and the re-infection of mumps in 6 and 2 patients, respectively. Moreover, second vaccine failure was suggested in the vaccinated patient.

Mutations in the gene encoding hypoxanthine-guanine phosphoribosyltransferase (HPRT) cause Lesch-Nyhan disease (LND) and its variants (LNV). Due to the technical problems for measuring the HPRT activity in vitro, discordances between the residual HPRT activity and the clinical severity were found. 5-Phosphoribosyl 1-pyrophosphate (PRPP) is a substrate for HPRT. Since increased PRPP concentrations were observed in erythrocytes from patients with LND and LNV, we have turned our attention to erythrocyte PRPP as a biomarker for the phenotype classification. In the present work, a method for determination of PRPP concentration in erythrocyte was developed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with multiple reaction monitoring (MRM). Packed erythrocyte samples were deproteinized by heating and the supernatants were injected into the LC-MS/MS system. All measurement results showed good precision with RSD6%. PRPP concentrations of nine normal male subjects, four male patents with LND and six male patients with LNV were compared. The PRPP concentrations in erythrocyte from patients with LND were markedly increased compared with those from normal subjects, and those from patients with LNV were also increased but the degree was smaller than those with LND. The increase pattern of PRPP concentration in erythrocyte from patients with HPRT deficiency was consistent with the respective phenotypes and was correlated with the disease severity. PRPP concentration was suggested to give us supportive information for the diagnosis and the phenotype classification of LND and LNV.

Background: Cerebral venous sinus thrombosis (CVT) occurs commonly in young female adults and is caused by various risk factors. Our aim was to determine the incidence, clinical characteristics, and risk factors of Japanese CVT patients. Patients and methods: We performed a retrospective study of CVT patients from January 2010 to June 2015. In the patients who had hyperhomocysteinemia, vitamin levels were measured. To define the clinical characteristics in patients with hyperhomocysteinemia, we statistically compared them to those patients with normal levels of homocysteine. Results: Sixteen patients (aged 54.6 ± 17.7 years; 13 men and 3 women) were included. The incidence of CVT was 0.23% among all types of strokes or 0.30% of acute ischemic strokes, which was lower than previously reported. The patients were characterized by advanced age, low frequency of headaches, and few female patients, especially female patients using oral contraceptives. The predisposing conditions included a notably high incidence of hyperhomocysteinemia (56.3%). They also included deficiencies of folate, vitamin B12, vitamin B6, or combined deficiencies. Marked hyperhomocysteinemia over 100 nmol/ml was noted in combined deficiencies. Conclusions: CVT in Japan commonly occurred in older males. The prevalence of hyperhomocysteinemia as a risk factor of CVT was high, and the main underlying disorders were folate and vitamin B12 or B6 deficiencies. This is clinically important, because these acquired risks can be corrected by supplementation therapy to prevent the recurrence of CVT.

An 18-year-old man was admitted to our hospital because of convulsive seizure. He had psychomotor retardation and intellectual disability from childhood, and had been diagnosed with attention deficit-hyperactivity disorder when he was 12 years old. He showed mental deficit (Wechsler Adult Intelligence Scale-Revised: IQ 52) and tendon hyperreflexia without pathological reflexes, but no involuntary movements or self-injurious behavior. As he had hyperuricemia, we measured the activity of hypoxanthine-guanine phosphoribosyltransferase (HPRT) and adenine phosphoribosyltransferase (APRT) in erythrocytes. While HPRT activity had decreased to 57.4% of normal, APRT activity had increased to 140.5% of normal. Genetic analysis revealed a single-base substitution (c.179A>G) in the third exon of the HPRT gene, which resulted in a missense mutation (p.H60R) of the 60th amino acid. His mother was a heterozygous carrier of this mutation and presented partial deficiency (73.3%) of HPRT activity. Lesch-Nyhan disease is a neurogenetic disorder caused by complete deficiency of the enzyme HPRT. Variant forms of the disease caused by partial deficiency of HPRT do not show the typical clinical features, or show only mild neurological manifestations; these diseases are jointly referred to as HPRT-related neurological disease (HRND). The present case was unique in that the patient diagnosed as having HRND showed relatively higher HPRT residual activity in erythrocytes.

Background Underweight patients have recently been reported as a group with a high risk of poststroke death. Anemia also increases mortality rates in stroke patients. However, the causal associations between body weight and anemia resulting in stroke-related death remain unclear. We examined the association of weight status and hemoglobin levels with 3-month mortality after ischemic stroke. Methods The study enrolled all consecutive patients with acute ischemic stroke and no history of stroke admitted to our hospital between January 2010 and December 2013. The patients were categorized into 4 body mass index (BMI) categories (underweight, normal-weight, overweight, and obese). Anemia was evaluated according to the World Health Organization criteria (men, Results A total of 1733 acute ischemic stroke patients (149 underweight, BMI 2 ; 1076 normal-weight, BMI = 18.5-24.9 kg/m 2 ; 436 overweight, BMI = 25-29.9 kg/m 2 ; and 72 obese, BMI > 30 kg/m 2 ) were included. Death within 3 months occurred in 65 patients (underweight, 10.1%; normal-weight, 3.4%; overweight, 2.3%; and obese, 5.6%). Compared to nonanemic patients, those with anemia (n = 329, 19.0%) had lower BMI (21.8 kg/m 2 versus 23.7 kg/m 2 , P .001) and higher mortality rates (9.1% versus 2.5%, P .001). Underweight status was associated with 3-month mortality after adjusting for age, sex, comorbidities, and initial stroke severity. However, in the models that included laboratory findings, it was anemia status (odds ratio, 2.81; 95% confidence interval, 1.46-5.43), not underweight status, that was independently associated with 3-month mortality. Conclusion Anemia on admission was associated with stroke mortality independent of underweight status.

We performed stent placement under intravascular ultrasound (IVUS), without the use of contrast medium, in a male patient in his 70s who had vertebral artery origin stenosis and decreased renal function. Satisfactory dilatation was achieved without complications, and the patient remained asymptomatic at 2 years of follow-up. We now report the details of this procedure. Stent placement under IVUS guidance may be useful in patients in whom contrast medium is contraindicated.

A 39-year-old man was suffered from bacterial meningitis spread from sphenoid sinusitis. During the first several days of the hospitalization, his clinical and laboratory findings were improved by the antibiotics. But he developed impaired consciousness and paraparesis on the sixth hospital day. A CT scan of the brain revealed pneumocephalus with compression of frontal lobes and the widening of the interhemispheric space between the tips of the frontal lobes, which was known as "Mount Fuji sign". Tension pneumocephalus was diagnosed on the basis of the clinical symptoms and the characteristic CT findings. As the bacterial meningitis itself was improving, the surgical treatment was not performed, but the antibiotics therapy continued. He gradually recovered and discharged without any other complications. The mechanism of tension pneumocephalus could not be disclosed. However, it was speculated that tension pneumocephalus was formed due to combined conditions of following factors; the fistula formation between sphenoid sinus and subdural space, the reduced CSF pressure on lumbar puncture, and a ball-valve mechanism though the fistula. We would emphasize that "Mount Fuji sign"on CT or MRI was the important finding to diagnose tension pneumocephalus.

It is important to determine the usage of anticoagulants by defining the actual risk of cardioembolic stroke in patients with old myocardial infarction. In the present study, we aimed to more precisely evaluate the risks of each segment associated with cardioembolic stroke using a 16-segment model. The usage of the plasma brain natriuretic peptide (BNP) associated with cardioembolic stroke was also evaluated in comparison with a left ventricle ejection fraction less than 40%.There were a total of 190 ischemic stroke patients who had premorbid myocardial infarction. The study included a total of 143 ischemic stroke patients with old myocardial infarction who were available for evaluation and excluded patients with atrial fibrillation or acute myocardial infarction. Their left ventricle wall motion abnormality and the level of plasma BNP at their admission were analyzed.Hypertension and a plasma BNP level of 206.9 pg/mL or higher, determined from the receiver operating characteristic curve, were independently associated with cardioembolic stroke (χ(2) = 35.6, R(2) = .30, P .001). Adjusting for these factors, statistically independent high risk was observed at the basal-inferior, basal-inferolateral, mid-anterior, mid-anteroseptal, apical-anterior, and apical-septal left ventricles.High plasma BNP levels and left ventricular wall motion abnormalities in the segments perfused with left anterior descending coronary artery or right coronary artery show a high risk for cardioembolic stroke in patients with old myocardial infarction. Considering these factors, it could be possible to more precisely define the risk of cardioembolic stroke and to perform appropriate antithrombotic treatments in old myocardial infarction patients.

Objective: Chloroquine modulates autophagocytic protein degradation in the lysosome system, thereby inducing the formation of rimmed vacuoles consisting of autophagosomes and autolysosomes in skeletal muscle. The goal of this study was to investigate the contribution of the lysosomal system, particularly autophagosome formation (an autophagic process) at the molecular level, to the abnormal accumulation of vacuoles in an experimental model of chloroquine-induced myopathy. Methods: Histological, immunohistochemical and semiquantitative reverse transcriptase-polymerase chain reaction studies were performed on innervated and denervated rat soleus muscles after treatment with either saline or chloroquine. Results: Accumulation of rimmed vacuoles was observed only in chloroquine-treated denervated muscles. Microtubule-associated protein-1 light chain-3 (LC3) protein and mRNA levels were significantly increased exclusively in denervated muscles from chloroquine-treated rats, whereas Apg5 and Apg12 mRNA levels did not change significantly. Further, the mRNA levels of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE), which are associated with distal myopathy with rimmed vacuoles showing numerous rimmed vacuoles in its skeletal muscle, were not decreased in denervatedmuscles treated with chloroquine. Conclusions: LC3 mRNA may increase in association with rimmed vacuole formation in denervated muscles from chloroquine-treated rats, suggesting an increase in autophagy at the molecular level. Abnormal accumulation of rimmed vacuoles in this myopathy does not appear to be mediated by inhibition of autophagosome-related genes or GNE gene.

In this study, we assessed 11 patients who were definitively diagnosed with tuberous sclerosis complex (TSC) based on the accepted clinical diagnostic criteria (Roach, 1998). We compared the clinical and radiological findings of six adult-onset TSC cases (group A) and five child-onset TSC cases (group B). The prevalence rates of generalized tonic-clonic convulsions at onset, mental retardation, facial angiofibroma, and epilepsy were lower in group A than in B group. The number of cortical tubers and subependymal nodules on brain magnetic resonance (MR) and computed tomography (CT) images were also lower in group A. The number of cerebral white matter radial migration lines was similar in both groups. Cortical tubers were most frequently observed in the frontal lobe in both groups. The number of cortical tubers and subependymal nodules did not correlate with the presence of epilepsy or mental retardation. Extra-brain lesions in lung, kidney, and bone were recognized in both groups, and no specific lesions were noted in group A.

A 74-year-old woman was clinically diagnosed with possible amyotrophic lateral sclerosis (ALS) and was administered 100 mg/day of riluzole. After 2 months, she developed dyspnea and experienced gradual difficulty walking. Chest computed tomography revealed ground-glass opacity and consolidation in the lower lobes of both the lungs, thereby suggesting a diagnosis of interstitial pneumonia. Because the condition was suspected to be drug-induced, riluzole administration was discontinued and steroid (methylprednisolone) pulse therapy (1,000 mg/day, 3 days) was started. Her symptoms and radiological findings improved immediately. At 16 months later, she wanted to take riluzole again. She had the similar interstitial pneumonia on the 4(th) day of the re-administration. Drug (riluzole)-induced lymphocyte stimulation tests (DLST) were negative two times. The symptoms of interstitial pneumonia, a rare adverse effect of riluzole, are very similar to worsening symptoms of ALS; therefore, patients with ALS receiving riluzole therapy should be carefully monitored.

BACKGROUND: Although hyperglycemia in acute stroke is associated with poor stroke outcomes, it remains unclear whether blood glucose variability are also associated with stroke outcomes. In this study, we examined the relationships between daily blood glucose variability and early neurological outcome in acute ischemic stroke patients with diabetes mellitus. METHODS: Subjects were a total of 329 acute ischemic stroke patients (216 male, 70.9 ± 9.6 years) who were either already undergoing treatment for diabetes or had a hemoglobin A1c level of >5.8% at admission from July 2006 to June 2009. The consecutive morning fasting blood glucose (BG) levels were evaluated during 7 days from admission and described as mean and successive variation (SV). The unfavorable outcome was defined by a modified Rankin Scale score of 4 to 6 at discharge. RESULTS: The patients with unfavorable outcome (n=86) were older (75.7 ± 10.5 vs. 69.2 ± 8.6 years, p SV levels was independently associated with unfavorable outcome (OR 1.023, 95%CI 1.004-1.042, p=0.015) using logistic regression analysis controlling age, sex hypertension systolic blood pressure, NIHSS score at admission and insulin use during hospitalization, which are selected using stepwise method. However mean BG levels did not remained as factor, which associated with unfavorable outcome with step wise method. CONCLUSION: Increased blood glucose variability, but not mean BG, was independently related to unfavorable outcome at discharge in acute ischemic stroke patients with diabetes mellitus.

A 39-year-old man was admitted to our hospital because of left frontal subcortical hemorrhage.When he was 22, he underwent an operation for aortic dilatation and aortic valve regurgitation, and he had been taking warfarin since then. At that hospital, he was diagnosed with Marfan syndrome (MFS) on the basis of his clinical features, but the diagnosis was not confirmed genetically. Head radiological imaging did not reveal the abnormal blood vessels causing subcortical hemorrhage, but T2* magnetic resonance imaging showed many micro-bleeds in the subcortical areas and basal ganglia. Moreover, cerebral angiography showed marked tortuous carotid and vertebral both arteries in his neck; these findings suggested the possibility of Loeys-Dietz syndrome. Genetic analysis revealed a single-base substitution (c.3713-3C>G) at the -3 position in the 29th intron of the FBN1 gene, encoding the fibrillin-1 protein. This mutation was not observed in his parents but was detected in his two sons who manifested the physical features of MFS. Therefore, this mutation was considered to be a de novo mutation exhibiting a new pathogenic mechanism involving abnormal splicing. The presented case is unique in that the patient with MFS showed subcortical hemorrhage and had a novel de novo mutation in the FBN1 gene.

From summer to autumn, we noted the occurrence of a small epidemic of aseptic meningitis in adults. Over the last 10 years, we have encountered 203 male (mean age, 34.6 ± 15.0 years) and 157 female (mean age, 35.6 ± 16.3 years) patients with aseptic meningitis. We could identify the causative virus in 17 (81%) of 21 cases during the abovementioned months in 2012. Identification rates of the virus in the stool, cerebrospinal fluid, throat swab, and serum samples were 71%, 67%, 42%, and 5%, respectively. The etiological viruses included enteroviruses in all cases, such as echovirus type 9 (E9) in 9 cases, echovirus type 6 (E6) in 4 cases, coxsackievirus type A9 in 1 case, and unknown type of enterovirus in 3 cases. No differences in the clinical manifestations and laboratory findings were noted between E9 meningitis and E6 meningitis. In addition, we countered 14 cases of mumps meningitis, 7 cases of varicella-zoster virus meningitis and 6 cases of herpes simplex meningitis during the last 10 years; these cases did not occur as an epidemic, but occurred sporadically. Cases of mumps meningitis were noted in all seasons, and cases of varicella-zoster virus meningitis were only noted from summer to winter. The etiology of epidemic aseptic meningitis in adults could be mainly due to enterovirus infection, and its prognosis was benign.

Recurrence of Guillain-Barre syndrome (GBS) and Fisher syndrome (FS) is uncommon. We retrospectively studied the cases of 93 consecutive patients with GBS and FS who were admitted to our hospital between January 2000 and March 2013. We analyzed the clinical features of and anti- glycolipid antibodies in patients who experienced recurrence. Of the 93 patients, 53, 37, and 3 had GBS, FS, and overlapping GBS and FS, respectively. There were 6 recurrences in 4 patients, all of whom were women; their onset age ranged from 26 to 51 years, and the average time to recurrence ranged from 9 months to 25 years. The recurrence rate of FS was 10.8%. On the recurrence, 2 patients showed FS (5.4%) and 2 patients showed overlap of GBS and FS (5.4%). All patients with recurrence showed good prognosis and increased anti-GQ1b glycolipid antibody levels both at the initial episode and at recurrence. Immunological examinations, including those for detecting changes in anti-glycolipid antibodies, are important for clarifying the pathomechanism of recurrence in GBS and FS.

Introduction: In acute stroke patients, ankle-brachial index (ABI)>0.9 is a clear predictor of increased stroke recurrence risk. However, it has not been defined whether clinical markers of peripheral arterial disease could predict the outcome of non-cardioembolic stroke. Hypothesis: We assessed the hypothesis that clinical markers (e.g. ABI and pulse wave velocity [PWV]) of peripheral arterial disease could predict the outcome of non-cardioembolic stroke. Methods: In our Brain Attack Center, 5432 acute ischemic stroke patients were admitted in January 2007 to December 2012. Among them, 686 lacunar or atherothrombotic stroke (TOAST criteria) patients (248 female and 438 male, median age 70.0 (range 35 to 96)) who admitted within 7 days after their onset and evaluated ABI and PWV during hospitalization were retrospectively examined in this study. Baseline characteristics and NIHSS scores at admission were noted, and modified Rankin scale (mRS) scores 3 months after stroke were evaluated. The patients were categorized into normal (≥0.9) and decreased ( Results: ABI was decreased in 28 (5.7%) of 496 good-outcome patients and 22 (11.6%) of 190 poor-outcome patients (p=0.008). PWV was increased in the patients with poor-outcome (2116.6±477.5 cm/s) compared with the patients with good-outcome (1934.9±415.6 cm/s, p2 =86.7, R 2 =0.107, n=686, p Conclusion: Our results showed that the poor-outcome of patients were predicted with ABI and PWV even after controlling age and NIHSS score. It is important to evaluate clinical markers (ABI and PWV) of peripheral arterial disease in the non-cardioembolic stroke patients.