Hemispheric Infarction Research Articles

Abstract TP330: Selective Brain Hypothermia Augmenting Neuroprotective Effects of Decompressive Craniectomy for Permanent Middle Cerebral Artery Infarction in a Rat Model

Objective: This study attempted to evaluate the combined effects of a decompressive craniectomy and prolonged selective brain hypothermia on large hemispheric infarction in a rat model. Methods: Permanent middle cerebral artery (MCA) infarction using an endovascular occlusion technique was created in the rats assigned to 4 groups. Normothermia was maintained without a craniectomy in group A (n = 20) as the controls, prolonged (> 44 hours), selective brain hypothermic treatment was performed on group B (n = 20), a craniectomy was performed on group C (n = 18), and prolonged, selective brain hypothermic treatment using a cooling coil implanted in the craniectomy site was combined with a craniectomy for group D (n = 18). Results: When compared with the controls, group B and C exhibited a significantly reduced infarct volume. Furthermore, group D showed a further reduction in the infarct volume (P < 0.01) and improved neurological score (P < 0.05) when compared with group C. This was associated with an increased neuronal cell count and reduced hyperactive microgia and hypertrophic astrocytes in the cortical penumbra (P < 0.01). Moreover, a higher preservation of normal-appearing axonal bundles and the blood brain barrier (BBB) was observed in the core infarct region at the caudoputamen. Conclusions: A decompressive craniectomy reduced the infarct volume and improved the neurological outcomes in a rat model of MCA infarction. Furthermore, when combined with prolonged selective brain hypothermia, significant additional benefits were observed for the neurological outcomes, infarct volume, and degree of neuroinflammation.

Maximum Decompressive Hemicraniectomy for Patients with Malignant Hemispheric Infarction.

ObjectiveThe authors applied maximum external decompression for malignant hemispheric infarction and investigated the functional outcome according to the patient age.MethodsTwenty-five patients with malignant hemispheric infarction were treated using a hemicraniectomy with maximum external decompression, comprising a larger (>14cm) hemicraniectomy, resection of the temporalis muscle and its fascia, spaciously expansive duraplasty, and approximation of the skin flap. The medical and diagnostic imaging records for the patients were reviewed, and 1-year functional outcome data obtained for the younger group (aged ≤ 60 years) and elderly group (aged > 60 years).ResultsThe patients (n=25) who underwent maximum surgical decompression revealed a minimal mortality rate (n=2, 8.0%). The patients (n=14) in the younger group all survived with mRS scores of 2 (n=1, 7.1%), 3 (n=7, 50.0%), 4 (n=3, 21.4%), or 5 (n=3, 21.4%). A majority of the younger patients (57.1% with mRS ≤3) lived with functional independence. When the 1-year mRS scores were dichotomized between favorable (mRS ≤3) and unfavorable (mRS ≥4) outcomes, the younger group had significantly more patients with a favorable outcome than the elderly group (57.1% versus 9.1%, p=0.033). In contrast, in the elderly group, most patients showed unfavorable outcomes with the mRS scores of 4 (n=5, 45.5%), 5 (n=3, 27.3%), or 6 (n=2, 18.2%), whereas only one patient showed favorable outcome (mRS 3). A majority of the elderly patients (45.5% with mRS 4) survived with moderately severe disability.ConclusionFor malignant hemispheric infarction, a hemicraniectomy with maximum external decompression was found to considerably increase survival with a favorable outcome in functional independence (mRS ≤3) for younger patients aged ≤60 years. It can be optimal surgical treatment for younger patients.

Stroke-related complications in large hemisphere infarction: incidence and influence on unfavorable outcome.

Objective:Neurological and medical complications are major causes of morbidity and mortality after ischemic stroke. This study aimed to identify the incidence of stroke-related complications following large hemisphere infarction (LHI) and to explore their influence on unfavorable outcome in LHI patients.Methods:We prospectively enrolled consecutive patients with LHI. The unfavorable outcome was defined as an modified Rankin Scale (mRS) score of 4–6 at 3 months. Multivariate logistic regression analysis was employed to identify the stroke-related complications associated with unfavorable outcome.Results:Of the 256 cases with LHI included, 41 (16.0%) died during hospitalization, 94 (36.7%) died and 140 (55.3%) patients had unfavorable outcome at 3 months. A total of 194 (75.8%) had at least one complication. The three most common medical complications were pneumonia (53.5%), electrolyte disorder (30.9%), and urinary incontinence (18.4%), and the three most common neurological complications were malignant brain edema (31.2%), hemorrhagic transformation (27.7%), and poststroke seizures (7.0%). Overall, LHI patients with unfavorable outcome had more frequent stroke-related complications (91.4% versus 55.8%, p < 0.001) than patients with favorable outcome. After adjusting for age, baseline National Institutes of Health Stroke Scale score, and other confounders, only malignant brain edema [odds ratios (OR) 19.76, 95% confidence interval (CI) 4.73–82.45] and pneumonia (OR 2.45, 95% CI 1.11–5.40) were independently associated with 3-month unfavorable outcome in patients with LHI.Conclusions:More than three-quarters of LHI patients have at least one stroke-related complication. LHI patients with the unfavorable outcome had stroke-related complications more frequently, whereas only malignant brain edema and pneumonia are independently associated with 3-month unfavorable outcome.

Outcome Prediction by 40-Hz Steady-State Response After Large Hemispheric Infarction

Background and Purpose: The 40-Hz steady state response (SSR) reflects early sensory processing and has the potential to differentiate disease severity. This study aims to evaluate the predictive value of 40-Hz SSRs on the prognosis of patients with large hemispheric infarction (LHI).Methods: We conducted a retrospective study in patients with LHI admitted to the neurological intensive care unit (NICU) of Nanfang Hospital, Southern Medical University, Guangzhou, China, between June 2008 and December 2014. Forty-hertz SSRs were recorded within 72 h of onset and categorized into 3 grades. The correlation between 40-Hz SSR grading and clinical outcome was examined.Results: Of the 97 eligible participants, 41 (42.3%) died within 30 days and 68 (70.1%) exhibited a poor outcome (modified Rankin Scale of 5 and 6) at 90 days after the onset of LHI. We found that 40-Hz SSRs correlated significantly with NIHSS scores at admission and patient outcome. Moreover, Grade III 40-Hz SSR (bilateral sine waves that either disappeared or were not clearly identifiable) had a specificity of 97% and a positive predictive value of 94% in predicting 90-days poor outcome; Grade III 40-Hz SSR also had a specificity of 91% and a positive predictive value of 74% in predicting 30-days mortality.Conclusions: 40-Hz SSR could be used as a simple and specific method in predicting poor prognosis after LHI.

Age-specific clinical characteristics and outcome in patients over 60years old with large hemispheric infarction.

ObjectiveWe aimed to investigate age‐specific clinical characteristics in patients aged >60 years with large hemispheric infarction (LHI).MethodsWe prospectively enrolled consecutive patients with LHI. Patients were divided into two groups: ≤60 vs. >60 years, and demographics, vascular risk factors, clinical feature, in‐hospital treatment, 3‐month mortality, and unfavorable outcome (defined as a mRS score of 4–6) rate were compared.ResultsOf the 256 cases included, 140 (54.7%) were older than 60 years. Compared with the younger, the older patients had higher rates of hypertension (66.4% vs. 31.0%), coronary heart disease (19.3% vs. 2.6%), atrial fibrillation (53.6% vs. 31.0%; all p < 0.001), more history of stroke (21.4% vs. 5.2%, p < 0.001), less history of rheumatic heart disease (16.4% vs. 30.1%, p = 0.009), and alcohol consumption (12.1% vs. 21.6%, p = 0.043). Cardio‐embolism is the most common stroke etiology regardless of age (55.7% and 38.8%, respectively). Furthermore, the elderly less frequently received decompressive hemicraniectomy (4.3% vs. 15.5%, p = 0.005) and mechanical ventilation (7.9% vs. 16.4%, p = 0.035) and had a higher frequency of stroke‐related complication (83.6% vs. 66.4%, p = 0.001). A total of 26 (18.6%) older patients and 15 (12.9%) younger patients died during hospitalization (p = 0.221), and 59 (42.1%) older patients and 35 (30.2%) younger patients died at 3 months (p = 0.061). Patient aged >60 years had significantly higher unfavorable outcome rate at 3 months (adjusted odds ratio, OR 4.30, 95% confidence interval [CI] 2.08–8.88; p < 0.05]. However, older age is not independently associated with 3‐month mortality (42.1% vs. 30.2%, p = 0.095 [log‐rank test]).ConclusionsLarge hemispheric infarction patients over 60 years old were a little more than those aged ≤60 years and constitute more than half of those suffered from malignant brain edema and two thirds of in‐hospital death and 3‐month mortality. The elderly had more cardio‐origin risk factors, received less aggressive hospital treatment, and showed higher risk of unfavorable outcome than the younger.

Cerebral blood flow features in chronic subcortical stroke: Lesion location-dependent study

We investigated the influence of lesion location on cerebral blood flow (CBF) in chronic subcortical stroke patients. Three-dimensional pseudocontinuous arterial spin labeling was employed to obtain CBF images in normal controls (NC) and patients with left hemisphere subcortical infarctions involving motor pathways. Stroke patients were divided into two subgroups based on the infarction location (basal ganglia (BS) or pontine (PS). We mapped CBF alterations in a voxel-wise manner and compared them to detect differences among groups with height-level false discovery rate correction. Regions with significant group differences were extracted to perform post hoc analyses among the BS, PS and NC groups using a general linear model with age, gender, years of education, and interval after stroke as covariates. The BS group displayed significantly increased CBF in the contralesional putamen relative to NC and significantly decreased CBF in the ipsilesional sensorimotor cortex, ipsilesional thalamus and contralesional cerebellum. The PS group displayed significantly increased CBF in the contralesional inferior frontal gyrus relative to both the NC and BS groups. Nevertheless, the PS group showed significantly decreased CBF mainly in the cerebellum. Our results suggest different alteration patterns of CBF in chronic stroke patients with different infarct locations within subcortical motor pathways, potentially providing important information for the initiation of individualized rehabilitation strategies for subcortical stroke patients involving different infarct types.

Influence of Strategic Cortical Infarctions on Pupillary Function.

Objective: Cortical activity, including cognitive and emotional processes, may influence pupillary function. The exact pathways and the site of cortical pupillary innervation remain elusive, however. We investigated the effects of select cortical strokes, i.e. ischemic infarcts affecting the insular cortex and prefrontal eye field, on pupillary function.Methods: Seventy-four patients with acute ischemic stroke, consecutively admitted to our institution from March to July 2018, were assessed 24 h after endovascular recanalization therapy (i.e., day 2 after the stroke), using automated pupillometry. Stroke location and volume and clinical severity (estimated by the Alberta Stroke Program Early CT Score and National Institute of Health Stroke Scale) were recorded. We excluded patients with posterior circulation stroke, intracranial pathology other than ischemic stroke, midline shift on computed tomography exceeding 5 millimeters or a history of eye disease. Pupillometry data from 25 neurologically normal patients with acute myocardial infarction were acquired for control.Results: Fifty stroke patients after thrombectomy were included for analysis. Twenty-five patients (50%) had insular cortex or prefrontal eye field involvement (group 1, strategic infarcts); 25 patients had infarcts located in other cerebral areas (group 2, other infarcts). The pupillary light reflex, as measured by constriction velocity and maximal/minimal pupillary diameters, was within physiological limits in all patients, including controls. However, while pupillary size and constriction velocities were correlated in all subjects, the correlation of size and dilatation velocity was absent in right-hemispheric infarcts (left hemisphere infarcts, group 1 (r2 = 0.15, p = 0.04), group 2 (r2 = 0.41, p = 0.0007); right hemisphere infarcts, group 1 (r2 = 0.008, p = 0.69); group 2 (r2 = 0.12, p = 0.08); controls (r2 = 0.29, p ≤ 0.0001).Conclusions: Cortical infarcts of the prefrontal eye field or insula do not impair the pupillary light reflex in humans. However, subtle changes may occur when the pupils dilate back to baseline, probably due to autonomic dysfunction. Replication is needed to explore the possible influence of hemispheric lateralization. We suggest that endovascular therapy for acute ischemic stroke may serve as a clinical research model for the study of acquired cortical lesions in humans.

Neurovascular Critical Care

Ischemic stroke and intracranial hemorrhage are among the most devastating and debilitating injuries in medicine. Initial management principles for acute ischemic stroke rely on prompt revascularization before the brain parenchymal is infarcted. Large hemispheric infarctions and malignant cerebral edema occur uncommonly in a subset of patients with acute ischemic stroke and are associated with high morbidity and mortality rates. The indications for decompressive hemicraniectomy for malignant cerebral edema are reviewed. Medical management of intraparenchymal hematomas and aneurysmal subarachnoid hemorrhage in the intensive care setting is emphasized. Important clinical sequelae of subarachnoid hemorrhage such as rebleeding, cerebral vasospasm, and cerebral salt wasting are reviewed. This review contains 5 figures, 4 tables and 52 references Key Words: acute ischemic stroke, cerebral aneurysm, cerebral vasospasm, decompressive hemicraniectomy, intracerebral hemorrhage, large hemispheric infarctions, subarachnoid hemorrhage, malignant cerebral edema

Facial motor and non-motor disabilities in patients with central facial paresis: a prospective cohort study.

Although central facial paresis (CFP) is a major symptom of stroke, there is a lack of studies on the motor and non-motor disabilities in stroke patients. A prospective cohort study was performed at admission for inpatient rehabilitation and discharge of post-stroke phase of 112 patients (44% female, median age: 64 years, median Barthel index: 70) with CFP. Motor function was evaluated using House-Brackmann grading, Sunnybrook grading and Stennert Index. Automated action unit (AU) analysis was performed to analyze mimic function in detail. Non-motor function was assessed using the Facial Disability Index (FDI) and the Facial Clinimetric Evaluation (FaCE). Median interval from stroke to rehabilitation was 21 days. Rehabilitation lasted 20 days. House-Brackmann grading was ≥ grade III for 79% at admission. AU activation in the lower face was significantly lower in patients with right hemispheric infarction compared to left hemispheric infarction (all p < 0.05). Median total FDI and FaCE score were 46.5 and 69, respectively. Facial grading and FDI/FaCE scores improved during inpatient rehabilitation (all p < 0.05). There was a significant increase of the activation of AU12 (Zygomaticus major muscle), AU13 (Levator anguli oris muscle), and AU24 (Orbicularis oris muscle) during inpatient rehabilitation (all p < 0.05). Multivariate analysis revealed that activation of AU10 (Levator labii superioris), AU12, AU17 (Depressor labii), and AU 38 (Nasalis) were independent predictors for better quality of life. These results demonstrate that CFP has a significant impact on patient's quality of life. Therapy of CFP with focus on specific AUs should be part of post-stroke rehabilitation.

CAR 10. Endarterectomy for Acute Symptomatic Thrombotic Occlusion of the Entire Extracranial Internal Carotid Artery: A Case Report

We report the case of a 60-year-old woman who was admitted with a sudden onset of numbness of the left upper extremity. Two weeks before admission, the patient presented with a right hemispheric transient ischemic attack and temporary right facial paresis. Duplex ultrasound and magnetic resonance (MR) angiography revealed an occlusion of the right internal carotid artery (ICA) as well as a high-grade stenosis of the left ICA with patency of the cerebral arteries (middle cerebral artery [MCA]). A cranial computed tomography scan showed a small hypodense lesion of the right hemisphere and several lacunar infarctions without signs of intracranial bleeding. An exploration of the right carotid bifurcation was performed, and an atherosclerotic plaque at the carotid bifurcation with a fresh clot downstream was found. Thrombectomy was performed using a 2F balloon catheter, resulting in a sufficient backflow from the ICA. In addition, thromboendarterectomy with patch plasty was performed. On the final intraoperative angiogram, the entire right ICA and the downstream intracranial vessels were patent. Intraoperative duplex ultrasound confirmed a sufficient hemodynamic profile without major turbulences. The postoperative MR angiogram confirmed patency of the ICA with an undisturbed perfusion of the right hemisphere. The postoperative course was uneventful; no neurologic symptoms occurred, and she was discharged on postoperative day 8. Six weeks later, the left ICA stenosis (North American Symptomatic Carotid Endarterectomy Trial [NASCET] 90%) was treated successfully by conventional thromboendarterectomy. During follow-up of 61 months, no neurologic or cardiac events occurred. A recurrent ICA stenosis was not detected. Comparing the perfusion of the right MCA with the preoperative MR angiogram, we conclude that a sufficient blood supply to the right MCA could probably not have been achieved by a simple left-sided carotid thromboendarterectomy. Whereas chronic ICA occlusion is generally accepted as a condition not suitable for extracranial reconstruction, our patient profited from revascularization as she suffered from an acute occlusion on top of a chronic stenosis. It remains uncertain which occluded artery should be explored and, specifically, at what time. In symptomatic patients, exploration of the ICA and carotid bifurcation might be justified to restore blood flow and to prevent a severe stroke event.

Tumour Emboli Causing Multifocal Ischemic Stroke from Intracardiac Malignant Solitary Fibrous Tumour

A 78-year-old woman presented to the emergency department with gait ataxia and diplopia. Her past medical history included the surgical resection of a phyllodes breast tumour 8 years prior, with no known recurrence. A computed tomography (CT) scan of the brain demonstrated multifocal right supratentorial hemispheric subacute infarcts in the frontoparietal, posterior temporal and occipital regions. The patient developed recurrent generalized seizures in hospital. Transesophageal echocardiogram demonstrated a large 2.7 × 1.8 × 0.8 cm mobile echogenic mass attached to the left posterior atrial wall. CT angiogram of the chest revealed the left atrial mass as well as a mass encasing the right bronchus intermedius. The patient opted for comfort care and passed away in hospital. Autopsy revealed the tumour to be a primary cardiac solitary fibrous tumour. We present a case of multifocal ischemic stroke and seizures secondary to tumor emboli originating from intracardiac solitary fibrous tumour.

Atypical clinical presentations in right hemispheric infarcts: complex stories beyond neurological examination and diffusion-weighted magnetic resonance imaging

Atypical clinical presentations in right hemispheric infarcts: complex stories beyond neurological examination and diffusion-weighted magnetic resonance imaging

Selective Brain Hypothermia Augmenting Neuroprotective Effects of Decompressive Craniectomy for Permanent Middle Cerebral Artery Infarction in a Rat Model

To evaluate the combined effects of a decompressive craniectomy and prolonged selective brain hypothermia on large hemispheric infarction in a rat model. Permanent middle cerebral artery infarction using an endovascular occlusion technique was created in rats assigned to 4 groups. Normothermia was maintained without a craniectomy in group A (n= 20) as the control, prolonged (>44 hours), selective brain hypothermic treatment was performed on group B (n= 20), a craniectomy was performed on group C (n= 18), and prolonged, selective brain hypothermic treatment using a cooling coil implanted in the craniectomy site was combined with a craniectomy for group D (n= 18). Group B and C exhibited a significantly reduced infarct volume when compared with the control. Furthermore, group D showed a significantly reduced infarct volume when compared with group C, plus a significantly improved neurologic score. These results for group D were associated with an increased neuronal cell count and reduced hyperactive microglia and hypertrophic astrocytes in the cortical penumbra (P < 0.01). Moreover, a greater preservation of normal-appearing axonal bundles and the blood-brain barrier was observed in the core infarct region at the caudoputamen. A decompressive craniectomy reduced the infarct volume and improved the neurologic outcomes in a rat model of middle cerebral artery infarction. Furthermore, when combined with prolonged selective brain hypothermia, significant additional benefits were observed for the neurologic outcomes, infarct volume, and degree of neuroinflammation.

Factors associated with favourable outcome in large hemispheric infarctions

BackgroundLarge hemispheric infarction (LHI) is a devastating condition with high mortality and poor functional outcome in most conservatively treated patients. The purpose of this study was to explore factors associated with favorable outcome in patients with LHI.MethodsWe prospectively enrolled consecutive patients with LHI. Favorable outcome was defined as a modified Rankin Scale (mRS) score of 0 to 3 at 90 days. Multivariate logistic regression analysis was employed to identify the independent factors associated with favorable outcome.ResultsTwo hundred fifty-six cases with LHI were identified: 41 (16.0%) died during hospitalization, 94 (36.7%) died at 3 month, and 113 (44.1%) survived with favorable outcome at day 90. Compared with patients with unfavorable outcome, the favorable cases were younger (55.8 ± 14.7 vs. 66.2 ± 14.1), had less history of hypertension (38.9% vs. 59.3%), lower baseline NIHSS score (median NIHSS score 11 vs. 17), lower blood pressure on admission (systolic 134.7 ± 24.9 vs. 145.1 ± 26.1 mmHg; diastolic 80.2 ± 14.9 vs. 86.9 ± 16.2 mmHg; respectively), lower level of baseline serum glucose (7.2 ± 3.3 vs. 8.2 ± 3.3 mmol/L), a lower frequency of stroke-related complications (55.8% vs. 91.4%), more use of antiplatelets (93.8% vs. 57.1%) and statins (46.9% vs. 25.7%) in the acute phase of stroke, but less use of osmotic agents (69.9% vs. 89.3%), mechanical ventilation (1.8% vs. 20.0%) or decompressive hemicraniectomy (1.8% vs. 15.7%). Multivariable analysis identified the following factors associated with favorable outcome: age (odds ratio, OR 0.95, 95% confidence interval [CI] 0.92–0.98, p < 0.001), baseline NIHSS score (OR 0.90, 95% CI 0.84–0.96, p = 0.002), statins used in acute phase (OR 2.49, 95% CI 1.10–5.65, p = 0.029), brain edema (OR 0.05, 95% CI 0.01–0.21, p < 0.001) and pneumonia (OR 0.42, 95% CI 0.19–0.93, p = 0.032).ConclusionMore than one third of patients with LHI have relatively favorable clinical outcomes at 90 days. Younger age, lower baseline NIHSS score, absence of brain edema and pneumonia, and statins used in the acute phase were associated with favorable outcome of patients with LHI at 90 days.

Abstract P198: WNK-SPAK-NKCC1 Cascade Activation Contributes to Worsened Brain Damage in Mice With Hypertension Co-Morbidity after Ischemic Stroke

Objectives: The WNK-SPAK/OSR1 kinase complex plays an important role in renal salt handling and pathogenesis of hypertension by regulating ion transporters and channels. Hypertension is the most common risk factor for stroke and stroke patients with hypertension comorbidity have worsened outcome with an increased risk of dependency or death. However, the mechanisms underlying the worsened ischemic stroke pathophysiology with hypertension comorbidity remain poorly defined. In this study, we investigated roles of the WNK-SPAK-NKCC1 signaling pathway in ischemic brain damage in mice with hypertension comorbidity. Methods: Hypertension was induced in C57BL/6j male mouse (12-15 weeks) by subcutaneous infusion of 1000 ng/kg/min angiotensin II (AngII, mini-osmotic pump) for two weeks. Permanent ischemic stroke was induced by permanent occlusion of the distal branches of the left middle cerebral artery (pd-MCAO). Brain tissues were harvested for immunoblot assessment of expression levels of NKCC1, SPAK/OSR1 or WNK1-4. Infarct volume and hemisphere swelling were determined by TTC staining, and behavioral deficits were analyzed by foot fault test, cylinder test and adhesive tape removal test. Results: pd-MCAO stimulated expression of WNK proteins (isoforms 1, 2, 4), total and phosphorylated SPAK/OSR1 and NKCC1 proteins in ischemic brains of the AngII-infused hypertensive mice compared to normotensive saline controls. In parallel with the increased activation of WNK-SPAK-NKCC1 signaling, hypertensive mice displayed significantly larger infarct volume and hemispheric swelling at 24 h after pd-MCAO compared to normotensive controls. Moreover, hypertensive mice exhibited a slow recovery of neurological function after ischemic stroke compared to normotensive counterparts as assessed by sensory-motor sensitive tests. Conclusions: These results suggest that activation of the WNK-SPAK-NKCC1 complex in hypertensive ischemic brains associates, at least in part, with the worsened brain damage and neurological deficits. Pharmacological inhibition of WNK-SPAK complex has therapeutic potentials for stroke therapy with hypertension comorbidity.

Prognosis and its predictors after treatment of unruptured intracranial spontaneous vertebral artery dissecting aneurysms with stent-related reconstructive techniques

Objective To evaluate the prognosis and its predictors after treatment of the unruptured intracranial spontaneous vertebral artery dissecting aneurysms (uis-VADAs) with stent-related reconstructive techniques. Methods Clinical data of 182 consecutive patients harboring 182 uis-VADAs, which were treated with the stent-related reconstructive techniques at Department of Neurosurgery, Changhai Hospital, Naval Military Medical University(92 cases) and Department of Interventional Neuroradiology, Beijing Tiantan Hospital, Capital Medical University(90 cases) from January 2009 to December 2015, were retrospectively reviewed and analyzed. The prognosis [favorable prognosis, modified Rankin Scale (mRS): 0-2; unfavorable prognosis, mRS: 3-6] and its predictors were evaluated and analyzed. Results The postoperative control angiography confirmed complete obliteration or near-complete obliteration in 135 (74.2%) cases and partial obliteration in 47 (25.8%) cases. Four (2.2%) patients suffered from periprocedural complications, which included stent thrombosis in 2 cases and occlusion of the distal posterior inferior cerebellar artery in 1 case with favorable prognosis, and the cerebellar hemisphere and brainstem multiple infarctions in 1 with unfavorable prognosis. Of 182 patients with uis-VADAs, 12 (6.6%) had unfavorable prognosis and included 4 (2.2%) deaths. In contrast, of 178 survivals with the median follow-up of 45 months (range: 12-72 months), 170(93.4%) patients had favorable prognosis. Follow-up angiography was available for 131 (73.6%) cases and reported recurrence in 23(17.6%). The multivariate logistic regression analysis indicated that preoperative cerebral infarction(OR=9.212, 95% CI: 2.154-39.395, P=0.003) and the largest diameter of VADAs (OR=1.112, 95%CI: 1.036-1.194, P=0.003) were predictors of unfavorable prognosis in the reconstructed uis-VADAs. Conclusions Patients with stent-related reconstructive treatment for uis-VADAs seem to have favorable prognosis with a low complication rate. The largest diameter of VADAs and preoperative cerebral infarction may be 2 independent predictors of unfavorable prognosis in the reconstructed uis-VADAs. Key words: Aneurysm, dissecting; Vertebral artery; Stents; Cerebral revascularization; Prognosis

Profile of intravenous glyburide for the prevention of cerebral edema following large hemispheric infarction: evidence to date.

Glyburide (also known as glibenclamide) is a second-generation sulfonylurea drug that inhibits sulfonylurea receptor 1 (Sur1) at nanomolar concentrations. Long used to target KATP (Sur1–Kir6.2) channels for the treatment of diabetes mellitus type 2, glyburide was recently repurposed to target Sur1–transient receptor potential melastatin 4 (Trpm4) channels in acute central nervous system injury. Discovered nearly two decades ago, SUR1–TRPM4 has emerged as a critical target in stroke, specifically in large hemispheric infarction, which is characterized by edema formation and life-threatening brain swelling. Following ischemia, SUR1–TRPM4 channels are transcriptionally upregulated in all cells of the neurovascular unit, including neurons, astrocytes, microglia, oligodendrocytes and microvascular endothelial cells. Work by several independent laboratories has linked SUR1–TRPM4 to edema formation, with blockade by glyburide reducing brain swelling and death in preclinical models. Recent work showed that, following ischemia, SUR1–TRPM4 co-assembles with aquaporin-4 to mediate cellular swelling of astrocytes, which contributes to brain swelling. Additionally, recent work linked SUR1–TRPM4 to secretion of matrix metalloproteinase-9 (MMP-9) induced by recombinant tissue plasminogen activator in activated brain endothelial cells, with blockade of SUR1–TRPM4 by glyburide reducing MMP-9 and hemorrhagic transformation in preclinical models with recombinant tissue plasminogen activator. The recently completed GAMES (Glyburide Advantage in Malignant Edema and Stroke) clinical trials on patients with large hemispheric infarctions treated with intravenous glyburide (RP-1127) revealed promising findings with regard to brain swelling (midline shift), MMP-9, functional outcomes and mortality. Here, we review key elements of the basic science, preclinical experiments and clinical studies, both retrospective and prospective, on glyburide in focal cerebral ischemia and stroke.

Clinical Effects and Differences in Neural Function Connectivity Revealed by MRI in Subacute Hemispheric and Brainstem Infarction Patients With Dysphagia After Swallowing Therapy.

Background: Early detection and intervention for post-stroke dysphagia could reduce the incidence of pulmonary complications and mortality. The aims of this study were to investigate the benefits of swallowing therapy in swallowing function and brain neuro-plasticity and to explore the relationship between swallowing function recovery and neuroplasticity after swallowing therapy in cerebral and brainstem stroke patients with dysphagia.Methods: We collected 17 subacute stroke patients with dysphagia (11 cerebral stroke patients with a median age of 76 years and 6 brainstem stroke patients with a median age of 70 years). Each patient received swallowing therapies during hospitalization. For each patient, functional oral intake scale (FOIS), functional dysphagia scale (FDS) and 8-point penetration-aspiration scale (PAS) in videofluoroscopy swallowing study (VFSS), and brain functional magnetic resonance imaging (fMRI) were evaluated before and after treatment.Results: FOIS (p = 0.003 in hemispheric group and p = 0.039 in brainstem group) and FDS (p = 0.006 in hemispheric group and p = 0.028 in brainstem group) were both significantly improved after treatment in hemispheric and brainstem stroke patients. In hemispheric stroke patients, changes in FOIS were related to changes of functional brain connectivity in the ventral default mode network (vDMN) of the precuneus in brain functional MRI (fMRI). In brainstem stroke patients, changes in FOIS were related to changes of functional brain connectivity in the left sensorimotor network (LSMN) of the left postcentral region characterized by brain fMRI.Conclusion: Both hemispheric and brainstem stroke patients with different swallowing difficulties showed improvements after swallowing training. For these two dysphagic stroke groups with corresponding etiologies, swallowing therapy could contribute to different functional neuroplasticity.

Influence of Pre-existing Cognitive Impairment on Rehabilitation Outcomes in Patients with Cerebral Infarction

The present study determined the effects of pre-existing cognitive impairment (PreCI) on the rehabilitation outcomes in patients with cerebral infarction. From June 2013 to August 2015, we classified 52 patients with unilateral cerebral hemispheric infarction into the PreCI and non-PreCI group based on three-dimensional stereotactic surface projection (3D-SSP) cerebral blood flow (CBF) decrease images and the past history of dementia. Furthermore we investigated the related clinical factors and functional independence measure (FIM). 1. Multivariate analysis revealed that the most important factors that affect total FIM at discharge were age, National institutes of Health Stroke Scale (NIHSS) and the Mini-Mental State Examination (MMSE) (R²=0.756). 2. The mean CBF values (P<0.05) were significantly associated with lesion volume, (P<0.001, P<0.05), the NIHSS score (P<0.001, P<0.01), the MMSE score (P<0.001, P<0.005), and total FIM (P<0.005, P<0.05) at discharge. 3. Both cognitive and motor FIM at discharge were significantly lower in the PreCI group (P<0.005, P<0.005). 4. The MMSE score of ZSAM abnormal group was significantly lower in the case of NIHSS score<10 of lesion and non lesion sides. PreCI, age, and neurological severity, affected the outcomes of stroke rehabilitation Therefore, the diagnosis of PreCI is considered important for effective stroke rehabilitation. (Received August 3, 2017; Accepted February 9, 2018; Published June 1, 2018).

Impact of Brain Atrophy on Early Neurological Deterioration and Outcome in Severe Ischemic Stroke Treated by Intravenous Thrombolysis

Background: Brain atrophy has shown a protective effect on the risk of early neurological deterioration (END) related to malignant edema in patients with hemispheric infarction but could be deleterious on the outcome. Aims: We aimed to assess whether brain atrophy has an impact on the risk of END and on the outcome in severe ischemic strokes after intravenous (IV) thrombolysis. Methods: From a prospective thrombolysis registry, 137 patients who had a National Institutes of Health Stroke Scale (NIHSS) ≥15, MRI at admission, and IV thrombolysis were included. Relative cerebral volume was calculated. END was defined as a ≥2-points deterioration 72-h NIHSS and a good outcome as a modified Rankin Scale (mRS) ≤2 at 3 months. A multiple logistic regression analysis with a stepwise backward procedure was performed. Results: END and a good outcome were observed, respectively, in 20 (14.6%) and 48 (37.5%) patients. In univariate analysis, predictors of END included age (p = 0.049), diabetes (p = 0.041), and parenchymal hemorrhage (p = 0.039). In multivariate analysis, age (p = 0.018) was significantly associated with END. Brain atrophy was not associated with END even in subgroup analysis according to the baseline infarct size. In univariate analysis, age (p = 0.003), prestroke mRS (p = 0.002), hypertension (p = 0.006), baseline NIHSS (p = 0.002), END (p = 0.002), proximal occlusion (p = 0.006), and recanalization at 24 h (p < 0.001) were associated with a good outcome. Only baseline NIHSS (p = 0.006) was associated with a good outcome after adjustment. Conclusions: We did not find any impact of brain atrophy on the risk of END and the outcome at 3 months in severe ischemic strokes after IV thrombolysis.