Warm Front Passage on the Previous Day Increased Ischemic Stroke Events.

BACKGROUND AND PURPOSE: The influence of a weather front passage is rarely evaluated on stroke events. We hypothesized that a weather front passage on the stroke onset day or during the previous days may play an important role in the incidence of stroke. METHODS: A multicenter retrospective study was conducted to evaluate the frequency of stroke events and their interaction with weather front passages. Consecutive acute stroke patients (n = 3935, 73.5 ± 12.4 years, 1610 females) who were admitted to 7 stroke hospitals in 3 cities from January 2012 to December 2013 were enrolled in this study. Multivariate Poisson regression models involving time lag variables were used to compare the daily rates of stroke events with the day of a weather front passage and the previous 6 days, adjusting for considerable influences of ambient temperature and atmospheric pressure. RESULTS: There were a total of 33 cold fronts and 13 warm fronts that passed over the 3 cities during the study period. The frequency of ischemic stroke significantly increased when a warm front passed on the previous day (risk ratio 1.34, 95% confidence interval 1.07-1.69, P= .016). CONCLUSIONS: This study indicated that a weather front passage on the previous days may be associated with the occurrence of stroke.

Screening for Fabry Disease in Japanese Patients with Young-Onset Stroke by Measuring α-Galactosidase A and Globotriaosylsphingosine.

BACKGROUND: Fabry disease is an X-linked lysosomal storage disorder caused by mutations in GLA, which encodes the enzyme α-galactosidase A (α-Gal A). Although the prevalence of Fabry disease in patients with stroke has been reported to range from 0% to 4%, few cohort studies have examined Japanese stroke patients. We aimed to clarify the prevalence of Fabry disease and the frequency of GLA mutations among patients with young-onset stroke in Japan. METHODS: From April 2015 to December 2016, we enrolled patients with young-onset (≤60 years old) ischemic stroke or intracerebral hemorrhage. We measured α-Gal A activity and the concentration of globotriaosylsphingosine in plasma. Genetic evaluations were performed in patients with low α-Gal A activity or high concentrations of globotriaosylsphingosine. RESULTS: Overall, 516 patients (median age of onset, 52 years old; 120 women) were consecutively enrolled in this study. Five patients (4 men and 1 woman) had low α-Gal A activity, and no patients were detected with the screen for plasma globotriaosylsphingosine levels. The genetic analysis did not identify a causative mutation responsible for classic Fabry disease in any of the patients, but 2 patients (.4%) carried the p.E66Q in GLA. CONCLUSIONS: No patient with Fabry disease was detected in our young-onset stroke cohort.

Multicenter Study of Intravenous Recombinant Tissue Plasminogen Activator Infusion around Hiroshima, Japan: The Hiroshima Acute Stroke Retrospective and Prospective Registry Study.

OBJECTIVE: Approximately 10 years have passed since intravenous (IV) recombinant tissue plasminogen activator therapy was approved in Japan. The aim of this retrospective study was to identify the effectiveness and safety of IV alteplase therapy with the Japanese original dose around Hiroshima via consideration of the patients' backgrounds, examination findings, and outcomes. METHODS: All consecutive patients with ischemic stroke who received IV alteplase therapy between October 2005 and October 2010 were registered. RESULTS: Four hundred twenty-nine patients with ischemic stroke (172 female [40.1%], mean age 73.7 ± 11.8 years) were registered. The proportion of patients over 75 years old was 51.5% (221 patients). The median National Institutes of Health Stroke Scale (NIHSS) scores at admission were 13 (interquartile range, 9-19), and the NIHSS scores 24 hours after alteplase infusion were 8 (interquartile range, 3-15). The proportion of intracerebral hemorrhage within the initial 36 hours was 20.2% (86 patients). After the multivariate regression analysis, a history of hypertension (odds ratio = 4.14; 95% confidence interval, 1.32-14.79; P = .01) and no recanalization (odds ratio = 10.10; 95% confidence interval, 3.03-39.33; P < .0001) were independently associated with a modified Rankin Scale (mRS) score of 2 or higher at 3 months. Patients over 75 years old were not significantly associated with an intracerebral hemorrhage within the initial 36 hours and an mRS score of 2 or higher at 3 months. CONCLUSIONS: The results of our study demonstrated that IV alteplase therapy with the Japanese original dose was effective and exhibited a safety profile similar to other studies. Moreover, we should not hesitate to IV alteplase therapy simply because of advanced age.

Effects of Meteorological Conditions on the Risk of Ischemic Stroke Events in Patients Treated with Alteplase--HEWS-tPA.

BACKGROUND: Predicting a day that presents a high risk for the occurrence of ischemic stroke events may enable health professionals to prepare for emergency stroke therapy more properly. We evaluated the association between meteorological conditions and the frequency of ischemic stroke events in Japanese patients. METHODS: Ischemic stroke patients (n = 299) who were treated with alteplase at 9 stroke hospitals in 3 restricted areas were examined. The daily rates of ischemic stroke events were compared with the daily mean thermo-hydrological index (THI), the atmospheric pressure, and the daily changes of these variables for the 6 days preceding an ischemic stroke event using Poisson regression analysis. RESULTS: We trisected onset days based on the THI (low-temperature, intermediate-temperature, and high-temperature), atmospheric pressure (low-pressure, intermediate-pressure, and high-pressure), changes in THI for preceding 6 days from the previous day (cooler, unchanged-temperature, and warmer), and changes in atmospheric pressure (decreased-pressure, unchanged-pressure, and increased-pressure). The frequency of ischemic stroke was significantly higher on low-temperature or high-pressure days (risk ratio, 1.398, P = .022; risk ratio, 1.374, P = .039), on warmer-temperature days, and when atmospheric pressure varied from the day before (P < .05). There were significantly lower risks for ischemic stroke events on cooler-temperature days, and higher risks were associated with a variation in atmospheric pressure 3 days before the onset from 4 days before (P < .05). CONCLUSIONS: There were higher risks for ischemic stroke events associated with low ambient temperature, high atmospheric pressure, increased temperature, and varied atmospheric pressure. Also, atmospheric pressure variation 3 days before may be associated.

The association between hyperintense vessel sign and final ischemic lesion differ in its location.

BACKGROUND: The hyperintense vessel sign (HVS) on fluid-attenuated inversion recovery images can frequently be detected in patients with acute cerebral infarction attributable to large artery stenosis or occlusion. The prognostic values and clinical characteristics of HVS remain to be elucidated. The aim of this study was to evaluate the association of HVS with ischemic lesions and severity of neurologic deficit. METHODS: A total of 96 consecutive acute ischemic stroke patients (54 women, median age 76.5 [range 39-97] years), who had symptomatic severe stenosis or occlusion in the proximal middle cerebral artery that was detected with magnetic resonance angiography within 24 hours of onset, were enrolled. The extent of HVS was graded by a systematic quantitative scoring system (the HVS distribution score) based on Alberta Stroke Program Early Computed Tomographic Score. RESULTS: An HVS was detected in 89 patients (93%) at admission, and the patients who displayed wider HVS distribution scores exhibited more severe neurologic deficits at admission (P<.05). The follow-up magnetic resonance imaging, which was obtained in 79 patients (82%), was performed an average of 13 days. The association between HVS distribution score and final ischemic lesions was strongly observed (n=67, P<.05) but not in the patients with intravenous thrombolysis (n=12, P=.06). CONCLUSIONS: Although the distribution of HVS reflected final ischemic lesion, this association might not apply to the patients with the thrombolysis treatment. The interpretation of HVS distribution score with acute ischemic stroke patients should be discussed dependent on thrombolysis.

Clinical Factors Predicting Voluntary Driving Cessation among Patients with Parkinson's Disease.

Factors that influence the decision of voluntary driving cessation in patients living with Parkinson's disease (PD) are still unclear. We aimed to reveal the factors affecting the decision of voluntary driving cessation in patients with PD. This hospital-based cross-sectional study recruited consecutive outpatients with PD. Data on sociodemographic and clinical characteristics and medication use were collected from the patients using semistructured interviews. Cognitive function was evaluated using the Japanese version of the Montreal Cognitive Assessment (MoCA-J). We excluded patients with dementia or motor impairment (Hoehn - Yahr stage > 3). We divided the patients into two groups, with and without voluntary driving cessation (D: driver; RD: retired driver), and conducted investigations using multivariate logistic regression analyses. Of the 40 patients, 8 (20.0%) voluntarily retired from driving. Patients who decided on driving cessation had a higher prevalence of freezing of gait (FOG) (D vs. RD, 25.0% vs. 87.5%; P = 0.001) and tended to have lower scores for attention in the MoCA-J (D vs. RD, 5.0 ± 1.2 vs. 4.1 ± 1.4; P = 0.086). Multivariable analysis showed that FOG was independently associated with driving cessation (odds ratio: 14.46, 95% confidence interval: 1.91-303.74). FOG was associated with voluntary driving cessation in patients with PD without dementia or severe motor impairment. Physicians should consider providing extensive social support to maintain patients' mobility and independence, especially if the patients have these clinical factors.

[Clinical characteristics of ischemic stroke in elderly patients with cancer].

AIM: We classified acute ischemic stroke patients with cancer according to their causal relations, and attempted to evaluate the clinical characteristics of ischemic stroke associated with cancer. METHODS: This is a retrospective study of all acute ischemic stroke patients admitted to our hospital between January 2006 and March 2009. Among acute ischemic stroke patients, we identified 30 patients with a history of cancer, or who developed cancer within 1 year from their ischemic stroke onset. There were 2 patients excluded from our evaluation because they had undergone extirpation of their cancer more than 5 years before stroke onset, and no recurrence of cancer within 5 years of stroke onset was noted. Finally, 28 patients were enrolled and evaluated in this study. Ischemic stroke was classified based on the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. In addition, we classified the patients according to their causal relations of ischemic stroke with cancer. RESULTS: The median patient age was 74 years (range, 56 to 91 years); 68% of patients were men. Of these, 8 (29%) were classified into an ischemic stroke related to cancer group. There was a higher prevalence of ischemic stroke related to cancer in patients under 75 years old with clinical stage IV cancer (p=0.02). D-dimer tended to be higher in those patients with ischemic stroke related to cancer in this study (p=0.13). CONCLUSION: Ischemic stroke related to cancer was found more frequently in patients under 75 years old with advanced cancer. Additionally, D-dimer tended to be higher in those patients with ischemic stroke related to cancer.

[Adult onset Alexander disease with a novel variant (S398F) in the glial fibrillary acidic protein gene].

We report a 58-year-old woman with adult onset Alexander disease. At the age of 54 she noticed numbness in bilateral legs and at 57 she developed left sided spastic gait. Her walking difficulty was gradually worsened and followed by the development of weakness in left arm, dysarthria and dysphagia. Her mother and elder brother also had similar clinical presentations which suggested an autosomal dominant neurological disorder. With MRI findings showing localized atrophy of medulla oblongata and upper cervical cord with hyperintensities on T2-weighted image, diagnosis of adult onset Alexander disease was made. We performed genetic analysis and found novel variant (S398F) in the glial fibrillary acidic protein gene. In case of slowly progressive myelopathy with bulbar palsy of unknown origin, especially those with atrophy limited to medulla oblongata and upper cervical cord, adult onset Alexander disease should be taken into consideration.

Novel Asp511Thr mutation in McArdle disease with acute kidney injury caused by rhabdomyolysis.

McArdle disease (glycogen storage disease type V) is a rare hereditary metabolic myopathy. It can be overlooked clinically because it often presents as chronic asymptomatic hypercreatine phosphokinasemia (hyperCKemia). However, vigorous exercise or infections can trigger severe rhabdomyolysis. We present the case of a patient with long-term idiopathic hyperCKemia who, after contracting an upper respiratory tract infection, developed severe rhabdomyolysis and acute kidney injury. Upon hemodialysis, his renal function recovered and CK levels fell to below baseline, and maintenance therapy with vitamin B6 was also started. A molecular diagnosis of McArdle disease was subsequently made. Whole-exome sequencing revealed homozygous c1538delG (p.Asp511Thr fs*28) mutations in the PYGM gene, which was a novel mutation. Therefore, when investigating idiopathic hyperCKemia, glycogen storage disorders should also be considered.

Various meteorological conditions exhibit both immediate and delayed influences on the risk of stroke events: The HEWS-stroke study.

We hypothesized that meteorological conditions on the onset day and conditions on the former days may play important roles in the modulation of physical conditions. Associations of meteorological factors and their changes in former days with stroke onset are of interest. We conducted a multicenter retrospective study to evaluate the frequency of stroke events and their interaction with meteorological conditions and their daily changes. Acute stroke patients (n = 3935, 73.5±12.4 years, 1610 females) who were admitted to 7 stroke hospitals in three restricted areas were enrolled in this study. Poisson regression models involving time-lag variables was used to compare daily rates of stroke events with mean thermo-hydrological index (THI), atmospheric pressure, and their daily changes. We divided onset days into quintiles based on the THI, atmospheric pressure, and their daily changes for the last 7 days. The frequencies of ischemic stroke significantly increased when THI varied either cooler or warmer from a previous day (extremely cooler, risk ratio (RR) 1.19, 95% confidence interval (CI) 1.05 to 1.34; extremely warmer, RR 1.16, 95% CI 1.03 to 1.31; r2 = 0.001 for the best regression, p = 0.001). Intracerebral hemorrhage frequencies significantly decreased on high-THI days (extremely high, RR 0.72, 95% CI 0.54 to 0.95; r2 = 0.013 for the best regression, p<0.001) and increased in high atmospheric pressure days (high, RR 1.31, 95% CI 1.04 to 1.65; r2 = 0.009 for the best regression, p<0.001). Additionally, even after adjusting for the THI on the onset day and its changes for the other days, intracerebral hemorrhage increased when THI got extremely cooler in 4 days prior (RR 1.33, 95% CI 1.03 to 1.71, r2 = 0.006 for the best regression, p<0.001). Various meteorological conditions may exhibit influences on stroke onset. And, when temperature cooled, there may be a possibility to show delayed influence on the frequency of intracerebral hemorrhage 4 days later.

Detection of cervical nerve root hypertrophy by ultrasonography in chronic inflammatory demyelinating polyradiculoneuropathy.

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, p<0.05, 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.

The optimal timing of antihypertensive medication administration for morning hypertension in patients with cerebral infarction.

Morning hypertension is an independent risk factor for cardiovascular diseases, particularly stroke. However, the optimal time at which to take antihypertensive medication to treat morning hypertension remains unclear. We prospectively enrolled elderly patients (over 65 years old) with morning hypertension who had suffered an ischemic stroke (or strokes). Additional treatments (one of six arms) were randomly administered for 10 weeks in the morning, in the evening or at bedtime (n=15 for each time point/medication). The patients measured their blood pressure and heart rate at home for 14 days prior to the intervention and for the final 14 days, and recorded the data in a blood pressure diary. The patients' urinary albumin/creatinine ratios were evaluated before and after the 10-week intervention. A total of 270 patients were enrolled in this study (mean age: 75.6±5.8 years; female/male ratio: 125/145). Their morning and evening systolic blood pressures were significantly decreased after following any of the study medication dosing schedules (P<0.001). However, the reductions in the differences between the morning and evening systolic blood pressures were significant only when the medication was taken in the evening or at bedtime (P<0.001 with repeated measures analysis of variance). Furthermore, the recovery rate from morning hypertension was also higher when the medication was taken in the evening (40.0%) or at bedtime (45.6%), rather than in the morning (22.2%; P=0.003 with the χ(2)-test). Antihypertensive medication taken in the evening or at bedtime is the most effective in treating morning hypertension when the patient adheres to the medication regimen.

Cancer-associated ischemic stroke is associated with elevated D-dimer and fibrin degradation product levels in acute ischemic stroke with advanced cancer.

AIM: Although several studies have reported various causes of ischemic stroke in patients with cancer, only a few have evaluated the clinical relevance of ischemic stroke pathogenesis to cancer. The aim of the present study was to elucidate the clinical characteristics of cancer-associated ischemic stroke. METHODS: We evaluated 154 ischemic stroke patients without cancer and 57 ischemic stroke patients with cancer who had either received continuous treatment for cancer within 5 years before to the onset of ischemic stroke, or who had been diagnosed with cancer within 1 year after the onset of ischemic stroke. Cancer patients were grouped into "cancer-associated ischemic stroke," the "conventional ischemic stroke," or "other." RESULTS: A total of 15 patients (26%) were classified into the cancer-associated ischemic stroke in cancer patients. In univariate analysis of the cancer-associated ischemic stroke and the others, there were significant differences in the prevalence of hypertension, hyperlipidemia and advanced cancer (clinical stage IV), and the levels of d-dimer, fibrin degradation product and hemoglobin. With multivariate regression analysis of those factors, the prevalence of hypertension, hyperlipidemia and advanced cancer (clinical stage IV), and the levels of D-dimer and fibrin degradation product remained as statistically independent factors, which were associated with cancer-associated ischemic stroke (n = 111, χ(2) =67.21, P < 0.0001). CONCLUSION: In acute ischemic stroke, the cancer-associated ischemic stroke is associated with elevated D-dimer and fibrin degradation products, even after controlling hypertension, hyperlipidemia and advanced cancer (clinical stage IV).

Blood pressure variability and prognosis in acute ischemic stroke with vascular compression on the rostral ventrolateral medulla (RVLM).

One of the known causes of hypertension is vascular compression on the rostral ventrolateral medulla (RVLM). However, it remains unknown whether RVLM vascular compression causes the significant variability in blood pressure observed during acute ischemic stroke. The purpose of this study was to evaluate differences in blood pressure variability and prognosis in acute ischemic stroke patients based on the presence or absence of RVLM vascular compression. We evaluated 56 patients with acute ischemic stroke. Blood pressure was measured every 6 h for 72 h after admission and evaluated with successive variation (SV). The presence of RVLM vascular compression was evaluated using time-of-flight 3D magnetic resonance imaging. Neurological severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS) at admission and 14 days after admission, and clinical improvement was determined by taking the difference in the NIHSS scores between admission and at 14 days. Patient clinical outcome was evaluated with the modified Rankin scale on discharge. Vascular compression of the RVLM was identified in 15 patients (26.8%). The proportion of patients showing clinical improvement was significantly higher in the non-compression group (odds ratio, 0.21 (95% CI = 0.06-0.78); P = 0.01). The SV value for systolic blood pressure was significantly higher in the compression group (P < 0.0001). We found that patients with RVLM vascular compression had a greater variability in blood pressure during the acute ischemic stroke phase, which may be related to poorer prognosis.

Therapeutic effects of postischemic treatment with hypotensive doses of an angiotensin II receptor blocker on transient focal cerebral ischemia.

BACKGROUND: Neurovascular protection against cerebral ischemia is not consistently observed with a postischemia hypotensive dose of candesartan. The aim of this study was to determine the levels of brain angiotensin II after reperfusion and the efficacy and therapeutic time window of postischemic treatments with hypotensive doses of candesartan for the treatment of cerebral ischemia. METHOD: Occlusions of the right middle cerebral artery (60 min) followed by reperfusion were performed using the thread method under halothane anesthesia in Sprague-Dawley (SD) rats. Protein levels of brain angiotensin II and mRNA levels of renin-angiotensin system components were evaluated following reperfusion (n=184 in total). Low-dose or high-dose treatments with candesartan cilexetil (1 or 10 mg/kg per day, respectively) were administered orally immediately following reperfusion once daily for 4 or 7 days (n = 119 in total). An additional group was treated with low-dose candesartan cilexetil after a 12-h delay based on the brain angiotensin II levels (n = 14). RESULTS: Levels of brain angiotensin II transiently increased 4-12 h after reperfusion, which followed an increase in angiotensinogen mRNA. Candesartan cilexetil treatments significantly reduced blood pressure (BP) in rats administered the high dose and moderately in rats receiving the low dose. A low dose of candesartan cilexetil reduced the infarct size, cerebral edema, and neurological deficits, whereas the high-dose treatments showed limited reductions. Furthermore, oxidative stress following reperfusion was reduced with the low-dose treatments. The therapeutic time window was open for at least 12 h after reperfusion when brain angiotensin II levels had peaked. CONCLUSION: Postischemic treatments using low hypotensive doses of candesartan cilexetil provided protection against cerebral ischemic injury and may have a clinically relevant therapeutic time window.