Arata Abe

Asymmetric dimethylarginine (ADMA) as a possible risk marker for ischemic stroke

BACKGROUND Asymmetric dimethylarginine (ADMA) affects vascular function by blocking nitric oxide synthesis. We examined the relationship of ADMA concentration to vascular risk factors in subjects who have undergone annual medical check-up. METHODS ADMA concentration, lipid profile and vascular risk factors were assessed during an annual medical examination in 116 subjects (mean age 58.7years). Univariate and multivariate analyses were carried out to assess factors associated with ADMA concentration. ADMA concentration was also assessed in 50 age-matched patients with ischemic stroke. RESULTS Mean serum ADMA concentration was significantly higher in the ischemic stroke patients than the medical check-up subjects (0.461+/-0.076 versus 0.433+/-0.056mumol/l; P=0.022). Univariate analysis showed that ADMA concentration in the medical check-up subjects was significantly associated with age, hypertension, dyslipidemia, fasting blood glucose, total and LDL cholesterol concentrations. Multiple stepwise linear regression analysis showed that hypertension (beta=0.25, P=0.008) and dyslipidemia (beta=0.19, P =0.048) were significant independent determinants of ADMA concentration. ADMA concentration increased progressively with number of vascular risk factors, with a significant (P=0.001) difference between subjects with no risk factors and subjects with > or =2 risk factors. CONCLUSIONS Serum ADMA concentration was significantly associated with vascular risk factors in subjects undergoing routine medical check-up. ADMA concentration warrants further examination as a possible marker of future development of ischemic stroke.

Valproic acid ameliorates ischemic brain injury in hyperglycemic rats with permanent middle cerebral occlusion.

Valproic acid (VPA) is widely used for the clinical treatment of epilepsy. Previous studies have demonstrated that VPA ameliorates brain injury following experimental stroke. However, the effect of VPA in stroke models featuring comorbid conditions has not been fully explored. In this study, we investigate the effects of VPA on permanent ischemic stroke with hyperglycemia. Hyperglycemia was induced by streptozotocin (STZ) injection 3 days before. Test animals received a single injection of VPA immediately after induction of ischemia. Control animals received occlusion and physiological saline injection, or STZ, occlusion, and saline. Magnetic resonance imaging of cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) was performed 60 min after ischemia. Infarct volume, neurological deficits, rotarod test performance, and immunohistological markers were assessed 3 days after ischemia. Hyperglycemia significantly expanded the area of decreased of CBF and ADC, and increased the number of myeloperoxidase-positive cells, ionized calcium binding adapter molecule 1-positive cells, inducible nitric oxide synthase-positive cells, von Willebrand factor-positive cells, and Fluoro-Jade C-positive cells in the ischemic boundary zone, which was accompanied by increased infarct volume and deteriorated neurological deficit and rotarod test compared with normoglycemia (P < 0.05). VPA significantly alleviated the aggravation of functional outcome accompanied by suppressing these inflammation, endothelial injury, and neuronal degeneration compared with saline-treated group (P < 0.05). A single injection of VPA following permanent ischemia in STZ-induced hyperglycemic rats ameliorates neurological deficits and reduces neuronal degeneration by inhibiting inflammation and endovascular injury. VPA may be promising as a candidate therapy for human stroke.

Low free triiodothyronine predicts poor functional outcome after acute ischemic stroke

BACKGROUND AND PURPOSE The aim of this study was to investigate the association of admission serum thyroid hormone concentration with clinical characteristics and functional outcomes in patients after acute ischemic stroke. METHODS We retrospectively enrolled 398 consecutive patients admitted to our stroke center between July 2010 and April 2012. Serum thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were evaluated upon admission. Neurological severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS) upon admission and the modified Rankin Scale (mRS) upon discharge. Poor outcome was defined as a mRS score of 3-5 or death (mRS score 6). Separate analyses were conducted according to outcome and quartile serum FT3 concentration. RESULTS In total, 164 patients (41.2%) demonstrated a poor outcome. Age, male gender, blood glucose level, arterial fibrillation, dyslipidemia, smoking, NIHSS score, cardioembolic stroke type, and periventricular hyperintensities, but not FT4 or TSH, were significantly associated with poor functional outcome. Furthermore, poor functional outcome was independently associated with low FT3 (<2.29pg/mL). In comparisons between FT3 quartiles (Q1 [≤2.11pg/mL], Q2 [2.12-2.45pg/mL], Q3 [2.46-2.77pg/mL], Q4 [≥2.78pg/mL]), patients with poor outcomes were more frequent in Q1 than in Q4 after multivariate adjustment. Death was more frequent in Q1 than in Q4 after adjustment for risk factors and comorbidities, but this difference was non-significant after additional adjustment for age and NIHSS score. CONCLUSIONS Our data suggest that a lower FT3 value upon admission may predict a poor functional outcome in patients with acute ischemic stroke. Further large-scale prospective studies are required to clarify the role of thyroid hormone in the acute phase of ischemic stroke.

Symptomatic Middle Cerebral Artery Stenosis Treated by Percutaneous Transluminal Angioplasty: Improvement of Cerebrovascular Reserves

This study evaluated the recoveries of cerebrovascular reserves (CVR) after applying percutaneous transluminal angioplasty (PTA) to patients with symptomatic middle cerebral artery (MCA) stenosis of varying severity. The patients were submitted to single photon emission computed tomography (SPECT) to obtain their regional cerebral blood flows at resting stage (rCBFrest) and acetazolamide-challenged CBF in five regions of interest (ROIs), including the MCA, on the ipsilateral and contralateral sides of the hemisphere. rCVR values were then calculated from these CBF data to evaluate the CVR recoveries after PTA treatment. When the PTA effects were statistically analyzed of the patients dichotomized into more severe (n=9) and less severe (n=5) groups, distinctly significant ROI-specific PTA effectiveness was observed for CVR rather than CBF values in the patients of the severer group.

Recovery of Cerebrovascular Reserves after Stenting for Symptomatic Carotid Artery Stenosis

Although a decrease in cerebrovascular reserves (CVR) is known to enhance the risk of stroke, changes in this parameter after carotid artery stenting (CAS) have rarely been investigated. The present study is the first to compare CVR recoveries after applying CAS to patients with symptomatic carotid artery disease. CAS was performed for 31 consecutive patients with symptomatic carotid artery disease. They underwent acetazolamide-challenged single photon emission computed tomography (SPECT) before and after CAS to obtain data on resting stage cerebral blood flow (CBFrest values) in various regions of interest (ROIs) defined by a three-dimensional stereotactic ROI template. CVR values on ipsilateral and contralateral hemispheric sides were then calculated based on the CBFrest data. The 31 patients were dichotomized into unilateral (n=22) and bilateral (n=9) lesion groups, and no significant between-group differences were observed in CBFrest before and after CAS. In the unilateral group, there were no differences in CVR values before and after CAS. In the bilateral group, however, the CVR values significantly increased in nearly all the investigated ROIs on the contralateral side. Also, the hemispheric CVR values on both sides significantly increased after CAS in the bilateral group, while no such increase was observed in the unilateral group. CAS in patients with symptomatic bilateral carotid artery disease has the potential utility for their haemodynamic improvement even on the contralateral hemispheric side.

Nicergoline Increases Serum Substance P Levels in Patients with an Ischaemic Stroke

Background: Aspiration pneumonia is one of the most important complications following ischaemic stroke, and a leading cause of mortality in stroke patients. This is particularly prevalent in patients with involvement of the basal ganglia, which may be due to impaired neurotransmission through lack of production of substance P. Methods: Consecutive patients in the chronic stage, 1–3 months after cerebral ischaemic infarction, were assessed for basal ganglia involvement by magnetic resonance imaging. The patients were randomised to 4 weeks of treatment with (n = 25) or without (n = 25) nicergoline (15 mg t.i.d.). Serum concentration of substance P was measured by radioimmunoassay. Results: At entry to the study, mean concentration of substance P was significantly (p < 0.001) lower in patients with bilateral basal ganglia lesions than in patients with no or unilateral basal ganglia involvement. Nicergoline administration caused a significant (p = 0.021) increase from baseline in mean substance P concentration. No significant change was seen in the nicergoline-untreated patients (p = 0.626). Among the patients who received nicergoline, 11 patients had bilateral basal ganglia involvement and there was no significant mean change in substance P in these patients, whereas there was a significant increase (p = 0.032) in the 14 nicergoline-treated patients with no or unilateral basal ganglia involvement. Conclusions: The present study suggests a possible effect of nicergoline to increase substance P level in ischaemic stroke patients with partial damage to basal ganglia, who have a decreased swallowing response and consequent risk of aspiration pneumonia. Further trials of nicergoline treatment in patients at risk for aspiration pneumonia are warranted.

Limb-shaking TIA: Cortical myoclonus associated with ICA stenosis

Limb-shaking associated with steno-occlusion of the internal carotid artery (ICA) was first reported by Miller Fisher1 in 1962, and is characterized by brief, jerky, coarse, involuntary movements involving an arm or leg. Limb-shaking TIA is an under-recognized manifestation of an intracranial and extracranial carotid occlusion or severe stenosis. Although hemodynamic compromise has been suggested to be associated with shaking movements, the pathogenic nature of this symptom remains unclear. Neurophysiologic evaluation of this movement disorder would be useful, but the attack is rare and typically lasts less than 5 minutes.2 Thus, few reports have investigated this hyperkinetic phenomenon under neurophysiologic assessment.3

Feasibility of using magnetic resonance imaging as a screening tool for acute stroke thrombolysis.

BACKGROUND Feasibility of performing MRI first for suspected hyperacute stroke patients in real-world practice has not been fully examined. Moreover, most past studies of reducing door-to-needle time (DNT) in intravenous thrombolysis were conducted using CT. The aim of this study was to evaluate the feasibility of an MRI-first policy and examine the effects of a quality improvement (QI) process for reducing DNT using MRI. METHODS From January 2014 to August 2015, consecutive acute stroke patients who were treated with thrombolysis were prospectively enrolled into the present study. In principle, multimodal 1.5T-MRI was performed first for patients with suspected acute stroke. A step-by-step QI process for decreasing DNT, including prenotification by the emergency medical service, limiting the MRI sequence, and introduction of a rapid examination tool, was also implemented during this period. Time metrics for thrombolysis were compared between specific time periods. RESULTS A total of 73 patients (27 women; median age 74years) were included in the present study. More than 80% of the patients were screened with MRI. More patients were managed with the MRI-first policy in the late phase (p=0.018). DNT (83min in the early phase, 68min in the middle phase, and 54min in the late phase, p<0.001) was significantly reduced across phases. The percentage of patients with DNT<60min increased significantly across time periods (p<0.001). CONCLUSION An MRI-first policy was feasible, and DNT was substantially reduced with a QI process. This process may be applicable to other hospitals.

Painless transient monocular loss of vision resulting from angle-closure glaucoma.

The main symptoms of acute primary angle‐closure glaucoma (PACG) include pain in the head and/or the eyes in addition to the characteristic halo and blurred vision. When loss of vision is accompanied by such pain, PACG is usually suspected. However, no information has been available regarding painless acute angle‐closure glaucoma. Recently, we treated a patient with painless acute PACG mimicking amaurosis fugax as a type of transient ischemic attack. Generally, amaurosis fugax causes transient monocular loss of vision due to occlusion of the ophthalmic artery. The formation of microemboli derived from the heart or carotid artery and/or the occurrence of some hemodynamic abnormality due to arteriosclerosis is closely related to amaurosis fugax, and most cases are complicated by intracranial or extracranial arterial lesions. In the present case, we provisionally diagnosed transient amaurosis fugax which, however, was shown by additional ocular testing to be painless PACG. Herein we describe our diagnostic process and the outcome.

Asymmetric dimethylarginine is related to the predicted stroke risk in middle-aged Japanese men

BACKGROUND Asymmetric dimethylarginine (ADMA) has recently been investigated as a risk marker for cardio- and cerebrovascular diseases. However, whether ADMA levels are related to the risk of stroke in the Japanese general population remains unclear. METHODS We examined 769 Japanese men (mean age, 47 ± 5 years) undergoing health examinations. Each subjects ADMA level and various vascular risk factors were assessed; the predicted 10-year stroke risk was calculated using the point-based prediction model from the Japan Public Health Center Study. RESULTS In a multiple linear regression analysis, age, body mass index, estimated glomerular filtration rate, and current smoking status were significant independent determinants of ADMA levels. A significant odds ratio (OR) for high predicted stroke risk (10-year risk ≥ 5%)was noted in the highest quartile of ADMA levels (OR, 2.47; 95% CI, 1.002-6.07), compared with the lowest quartile, after adjusting for potential confounding factors. A significant OR for high predicted stroke risk was also found for each standard deviation increment in ADMA level (adjusted OR, 1.46; 95% CI, 1.10-1.92). CONCLUSION Elevated ADMA levels were significantly associated with an increased predicted stroke risk, suggesting that measuring ADMA levels may be useful for identifying middle-aged Japanese men with a high risk of stroke.