Reversible Cerebral Ischemia Research Articles

In vivo study of the utility of selective intra-arterial injection of thiopental for neuroprotection in reversible cerebral ischemia.

Neuroprotective agents are needed to reduce cerebral damage during surgical or neurointerventional procedures including stroke patients. To evaluate if thiopental can be used as a neuroprotective agent when injected intra-arterially in a transient ischemia model. In total, 24 rabbits were studied as four groups of six animals. Group 1 served as the control group. In group 2, transient ischemia was obtained by intracarotid administration of degradable starch microspheres (DSM). Group 3 was administered thiopental intra-arterially via the carotid artery. Group 4 (experimental group) received both thiopental and DSM intra-arterially. DSM and thiopental were administered through a microcatheter placed into the common carotid artery via the central ear artery access. After sacrifice, apoptotic cells in the cerebral tissues of the animals were evaluated in H&E and TUNEL stained slides. There was a significant increase in the number of apoptotic glial or neuronal cells in group 2 compared to the control group and group 3. The mean number of both the apoptotic neuronal cells (6.8 ± 2.1 vs. 2.5 ± 1.3, P < 0.001) and the apoptotic glial cells (9.4 ± 3.1 vs. 4.6 ± 1.6, P < 0.001) were higher in group 2 compared to group 4. In addition, a higher level of neurological improvement was observed in group 4 compared to group 2 based on neurological assessment score. The intra-arterial administration of thiopental has a protective effect on both glial and neuronal cells during temporary cerebral ischemia in low doses.

Alzheimer's Disease Connected Genes in the Post-Ischemic Hippocampus and Temporal Cortex.

It is considered that brain ischemia can be causative connected to Alzheimer’s disease. In the CA1 and CA3 regions of the hippocampus and temporal cortex, genes related to Alzheimer’s disease, such as the amyloid protein precursor (APP), β-secretase (BACE1), presenilin 1 (PSEN1) and 2 (PSEN2), are deregulated by ischemia. The pattern of change in the CA1 area of the hippocampus covers all genes tested, and the changes occur at all post-ischemic times. In contrast, the pattern of gene changes in the CA3 subfield is much less intense, does not occur at all post-ischemic times, and is delayed in time post-ischemia relative to the CA1 field. Conversely, the pattern of gene alterations in the temporal cortex appears immediately after ischemia, and does not occur at all post-ischemic times and does not affect all genes. Evidence therefore suggests that various forms of dysregulation of the APP, BACE1 and PSEN1 and PSEN2 genes are associated with individual neuronal cell responses in the CA1 and CA3 areas of the hippocampus and temporal cortex with reversible cerebral ischemia. Scientific data indicate that an ischemic episode of the brain is a trigger of amyloidogenic processes. From the information provided, it appears that post-ischemic brain injury additionally activates neuronal death in the hippocampus and temporal cortex in an amyloid-dependent manner.

Chapter 22 - Neuromonitoring during descending aorta procedures

Thoraco-abdominal aneurysm (TAA) repair carries a significant risk of spinal cord infarction. The latter results from irreversible changes in the spinal cord arterial network, e.g., sacrifice of the segmental arteries. Intra-operative neurophysiology with somatosensory and especially motor evoked potential (SEP and MEP respectively) monitoring, has emerged as an effective tool to assess the efficiency of the collateral blood flow, detect reversible spinal cord ischemia and guide the peri-operative multidisciplinary management to prevent postoperative paraplegia. The main roles of such monitoring include diagnosis of spinal cord vs peripheral limb ischemia, titration of mean arterial pressure during aortic clamping, the guidance of selective re-implantation of critical segmental arteries, and management of hemodynamics in the immediate postoperative period. In addition, manipulation of the aortic arch and proximal descending aorta, adds the risk of cerebral infarction from both low flow state and/or thromboembolic events. As such, EEG monitoring may be a useful add-on for either assessment of the efficiency of cerebral cooling as a neuroprotective method and/or for detection and treatment of reversible cerebral ischemia. This chapter presents the multimodality approach to open TAA monitoring as a versatile tool for the prevention of devastating postoperative neurologic deficits.

Thrombectomy for anterior circulation stroke beyond 6 h from time last known well (AURORA): a systematic review and individual patient data meta-analysis

Trials examining the benefit of thrombectomy in anterior circulation proximal large vessel occlusion stroke have enrolled patients considered to have salvageable brain tissue, who were randomly assigned beyond 6 h and (depending on study protocol) up to 24 h from time last seen well. We aimed to estimate the benefit of thrombectomy overall and in prespecified subgroups through individual patient data meta-analysis. We did a systematic review and individual patient data meta-analysis between Jan 1, 2010, and March 1, 2021, of randomised controlled trials of endovascular stroke therapy. In the Analysis Of Pooled Data From Randomized Studies Of Thrombectomy More Than 6 Hours After Last Known Well (AURORA) collaboration, the primary outcome was disability on the modified Rankin Scale (mRS) at 90 days, analysed by ordinal logistic regression. Key safety outcomes were symptomatic intracerebral haemorrhage and mortality within 90 days. Patient level data from 505 individuals (n=266 intervention, n=239 control; mean age 68·6 years [SD 13·7], 259 [51·3%] women) were included from six trials that met inclusion criteria of 17 screened published randomised trials. Primary outcome analysis showed a benefit of thrombectomy with an unadjusted common odds ratio (OR) of 2·42 (95% CI 1·76-3·33; p<0·0001) and an adjusted common OR (for age, gender, baseline stroke severity, extent of infarction on baseline head CT, and time from onset to random assignment) of 2·54 (1·83-3·54; p<0·0001). Thrombectomy was associated with higher rates of independence in activities of daily living (mRS 0-2) than best medical therapy alone (122 [45·9%] of 266 vs 46 [19·3%] of 238; p<0·0001). No significant difference between intervention and control groups was found when analysing either 90-day mortality (44 [16·5%] of 266 vs 46 [19·3%] of 238) or symptomatic intracerebral haemorrhage (14 [5·3%] of 266 vs eight [3·3%] of 239). No heterogeneity of treatment effect was noted across subgroups defined by age, gender, baseline stroke severity, vessel occlusion site, baseline Alberta Stroke Program Early CT Score, and mode of presentation; treatment effect was stronger in patients randomly assigned within 12-24 h (common OR 5·86 [95% CI 3·14-10·94]) than those randomly assigned within 6-12 h (1·76 [1·18-2·62]; pinteraction=0·0087). These findings strengthen the evidence for benefit of endovascular thrombectomy in patients with evidence of reversible cerebral ischaemia across the 6-24 h time window and are relevant to clinical practice. Our findings suggest that in these patients, thrombectomy should not be withheld on the basis of mode of presentation or of the point in time of presentation within the 6-24 h time window. Stryker Neurovascular.

Late thrombectomy for ischaemic stroke

Patients with ischaemic stroke tend to delay seeking professional help compared with patients with acute myocardial infarction with ST elevation (STEMI). Moreover, for patients with STEMI, a diagnosis of ongoing ischaemia can be made with an electrocardiogram in the ambulance. The situation is vastly different for a patient who has had a stroke. Those with cortical infarcts—the case for most patients—are often not aware of their acute deficit, or they cannot communicate because of language problems. Moreover, patients with cerebral ischaemia do not have pain, as patients with STEMI do. They also typically do not wake up when a stroke occurs during sleep. Notification of the stroke to emergency services often depends on the alertness of partners and bystanders, and it should not be surprising that patients have delays in presenting to the emergency room, typically 3–4 h later than patients with a STEMI. 1 Al'Aref SJ Wong SC Swaminathan RV et al. Analysis of reperfusion time trends in patients with ST-elevation myocardial infarction across New York State from 2004 to 2012. Int J Cardiol. 2017; 232: 140-146 Summary Full Text Full Text PDF PubMed Scopus (5) Google Scholar , 2 de Havenon A Alexander MD Nogueira RG et al. Duration of symptomatic stroke and successful reperfusion with endovascular thrombectomy for anterior circulation large vessel occlusive stroke. J Neurointerv Surg. 2021; 01 (neurintsurg-2020-016961.) Google Scholar In patients arriving after more than 6 h from onset, diagnosis of ongoing ischaemia caused by intracranial large vessel occlusion has to be made with CT angiography and perfusion imaging, which further adds to the delay. Thrombectomy for anterior circulation stroke beyond 6 h from time last known well (AURORA): a systematic review and individual patient data meta-analysisThese findings strengthen the evidence for benefit of endovascular thrombectomy in patients with evidence of reversible cerebral ischaemia across the 6–24 h time window and are relevant to clinical practice. Our findings suggest that in these patients, thrombectomy should not be withheld on the basis of mode of presentation or of the point in time of presentation within the 6–24 h time window. Full-Text PDF

Neuroprotective Effects of a Novel Inhibitor of c-Jun N-Terminal Kinase in the Rat Model of Transient Focal Cerebral Ischemia.

A novel specific inhibitor of c-Jun N-terminal kinase, 11H-indeno[1,2-b]quinoxalin-11-one oxime sodium salt (IQ-1S), has a high affinity to JNK3 compared to JNK1/JNK2. The aim of this work was to study the mechanisms of neuroprotective activity of IQ-1S in the models of reversible focal cerebral ischemia (FCI) in Wistar rats. The animals were administered with an intraperitoneal injection of IQ-1S (5 and 25 mg/kg) or citicoline (500 mg/kg). Administration of IQ-1S exerted a pronounced dose-dependent neuroprotective effect, not inferior to the effects of citicoline. Administration of IQ-1S at doses of 5 and 25 mg/kg reduced the infarct size by 20% and 50%, respectively, 48 h after FCI, whereas administration of citicoline reduced the infarct size by 34%. The administration of IQ-1S was associated with a faster amelioration of neurological status. Control rats showed a 2.0-fold increase in phospho-c-Jun levels in the hippocampus compared to the corresponding values in sham-operated rats 4 h after FCI. Administration of IQ-1S at a dose of 25 mg/kg reduced JNK-dependent phosphorylation of c-Jun by 20%. Our findings suggest that IQ-1S inhibits JNK enzymatic activity in the hippocampus and protects against stroke injury when administered in the therapeutic and prophylactic regimen in the rat model of FCI.

Loss of interneurons and disruption of perineuronal nets in the cerebral cortex following hypoxia-ischaemia in near-term fetal sheep

Hypoxia-ischaemia (HI) in term infants is a common cause of brain injury and neurodevelopmental impairment. Development of gamma-aminobutyric acid (GABA)ergic circuitry in the cerebral cortex is a critical event in perinatal brain development. Perineuronal nets (PNNs) are specialised extracellular matrix structures that surround GABAergic interneurons, and are important for their function. Herein, we hypothesised that HI would reduce survival of cortical interneurons and disrupt PNNs in a near-term fetal sheep model of global cerebral ischaemia. Fetal sheep (0.85 gestation) received sham occlusion (n = 5) or 30 min of reversible cerebral ischaemia (HI group; n = 5), and were recovered for 7 days. Expression of interneurons (glutamate decarboxylase [GAD]+; parvalbumin [PV]+) and PNNs (Wisteria floribunda agglutinin, WFA) was assessed in the parasagittal cortex by immunohistochemistry. HI was associated with marked loss of both GAD+ and PV+ cortical interneurons (all layers of the parasagittal cortex and layer 6) and PNNs (layer 6). The expression and integrity of PNNs was also reduced on surviving GAD+ interneurons. There was a trend towards a linear correlation of the proportion of GAD+ neurons that were WFA+ with seizure burden (r2 = 0.76, p = 0.0534). Overall, these data indicate that HI may cause deficits in the cortical GABAergic system involving loss of interneurons and disruption of PNNs, which may contribute to the range of adverse neurological outcomes following perinatal brain injury.

A Marker of Cerebral Ischemia in Solid State Structures of Blood Serum.

Reversible cerebral ischemia of medium severity was reproduced in male Wistar rats by bilateral occlusion of the common carotid arteries. Solid-phase structures (anisomorphons) were obtained by marginal dehydration of the serum. Small focal isotropic defects in the serum anisomorphon texture were found in 100% cases during occlusion of the carotid arteries. Similar signs were detected in all patients with chronic cerebral ischemia, which proved specificity of this morphological marker of the disease.

Transient global cerebral ischemia induces rapid and sustained reorganization of synaptic structures

Ischemia can cause rapid neuronal damage. Previous studies have suggested that synaptic structures and cortical functions can be rescued if therapeutic interventions are applied in time, but the structural basis for this resilience remains incompletely understood. Here, we investigated the restoration of synaptic structures and postischemic plasticity of dendritic spines in the somatosensory cortices of mice by taking advantage of a reversible global cerebral ischemia model. Intravital two-photon imaging revealed that although dendritic structures were rapidly distorted after global ischemia, only a small percentage of spines were actually lost after transient ischemia. Electron microscopy indicated that most presynaptic electron-dense structures were still apposed to postsynaptic densities, and that the majority of disrupted synaptic structures were rapidly reinstated following reperfusion after transient ischemia. Repeated imaging suggested that restored dendrites survived the initial ischemia–reperfusion challenge. Importantly, spines on the restored dendrites underwent a rapid and sustained structural reorganization following transient ischemia. These findings suggested that disrupted synapses during transient ischemia could be rapidly restored after ischemia/reperfusion, and that restored dendritic structures remained plastic to rebuild the cortical network.

Prevention of ischemic complications during aneurysm surgery.

Ischemic complications during aneurysm surgery are a frequent cause of postoperative infarctions and new neurological deficits. In this article, we discuss imaging and neurophysiological tools that may help the surgeon to detect intraoperative ischemia. The strength of intraoperative digital subtraction angiography (DSA) is the full view of the arterial and venous vessel. DSA is the gold standard in complex and giant aneurysms, but due to certain disadvantages, it cannot be considered standard of care. Microvascular Doppler sonography is probably the fastest diagnostic tool and can quickly aid diagnosis of large vessel occlusions. Intraoperative indocyanine green videoangiography is the best tool to assess flow in perforating and larger arteries, as well as occlusion of the aneurysm sac. Intraoperative neurophysiological monitoring with somatosensory and motor evoked potentials indirectly measures blood flow by recording neuronal function. It covers all causes of intraoperative ischemia, provided that ischemia occurs in the brain areas under surveillance. However, every method has advantages and disadvantages. No single method is superior to the others in every aspect. Therefore, it is very important for the neurosurgeon to know the strengths and weaknesses of each tool in order to have them available, to know how to use them for each individual situation, and to be ready to apply them within the time window for reversible cerebral ischemia.

The role of AMPA-receptors in mechanisms of neuroprotective effect of cerebral ischemic postconditioning

Objective. The purpose of the study is to explore the role of AMPA receptors in the neuroprotective effect of ischemic postconditioning (IРost) in the model of reversible global forebrain ischemia in Mongolian gerbils. Design and methods. Reversible global cerebral ischemia was induced by bilateral occlusion of common carotid arteries in Mongolian gerbils for 7 minutes. IРost was induced by three 15-s episodes of reperfusion/reocclusion. Antagonist of AMPA receptors NBQX was administered intraperitoneally at 2 nd minute of ischemia at a dose of 30 mg/kg. In the early and delayed reperfusion period, the number of viable neurons in the CA1, CA2, CA, and CA4 fields of the hippocampus was estimated. Results. Reversible 7 minutes ischemia followed by 48 hours of reperfusion resulted in a significant reduction in the number of viable neurons in the fields CA1 and СА3 of the hippocampus, while in the late reperfusion period a significant reduction in the number of viable neurons was observed in fields CA1, СА3 and CA4. Application of IРost has led to an increase in the number of viable neurons in fields CA1 and CA3 in the early reperfusion period and in fields CA1, CA3 and CA4 — in delayed period. AMPA receptor antagonist NBQX attenuated neuroprotective effect of IPost to a level comparable with the effect of a separate application of NBQX for neurons in the CA1 and CA3 fields of the hippocampus. Conclusions . Along with other mechanisms, the activation of AMPA receptors might be implicated in the mechanisms of cerebral IPost.

The dichotomy of memantine treatment for ischemic stroke: dose-dependent protective and detrimental effects.

Excitotoxicity is a major contributor to cell death during the acute phase of ischemic stroke but aggressive pharmacological targeting of excitotoxicity has failed clinically. Here we investigated whether pretreatment with low doses of memantine, within the range currently used and well tolerated for the treatment of Alzheimer's disease, produce a protective effect in stroke. A coculture preparation exposed to modeled ischemia showed cell death associated with rapid glutamate rises and cytotoxic Ca2+ influx. Cell death was significantly enhanced in the presence of high memantine concentrations. However, low memantine concentrations significantly protected neurons and glia via excitotoxic cascade interruption. Mice were systemically administered a range of memantine doses (0.02, 0.2, 2, 10, and 20 mg/kg/day) starting 24 hours before 60 minutes reversible focal cerebral ischemia and continuing for a 48-hour recovery period. Low dose (0.2 mg/kg/day) memantine treatment significantly reduced lesion volume (by 30% to 50%) and improved behavioral outcomes in stroke lesions that had been separated into either small/striatal or large/striatocortical infarcts. However, higher doses of memantine (20 mg/kg/day) significantly increased injury. These results show that clinically established low doses of memantine should be considered for patients ‘at risk' of stroke, while higher doses are contraindicated.

Influence of cerebral global ischemia-reperfusion on succinate dehydrogenase activity in neurons of different neocortical layers

The aim of the study was to investigate changes in activity of succinate dehydrogenase (SDH) in cytoplasm of neurons of different cortical layers in early and late reperfusion period after global cerebral ischemia in rats. Reversible global cerebral ischemia was modeled by occlusion of the brachiocephalic trunk, left subclavian artery and left common carotid artery for 10 minutes and following reperfusion during 2 or 7 days. The SDH activity in cytoplasm of neurons of II, III and V cortical layers was determined histoenzymatically. It is shown that the SDH activity in neurons of the studied cortical layers was characterized by the increased reperfusion period to the 2 days with a subsequent increased activity of the reperfusion period to the 7 days. The change in the SDH activity in cytoplasm of cortical neurons depends on the particular cerebral layer and duration of postischemic reperfusion.

Computed Tomography Perfusion Imaging in the Selection of Acute Stroke Patients to Undergo Emergent Carotid Endarterectomy

Severe acute stroke patients with critical carotid stenosis or occlusion without intracranial thrombus typically do not undergo emergent carotid thromboendarterectomy (CEA) because of the risk of reperfusion-related intracranial hemorrhage. Past studies have not consistently demonstrated benefit of early operative intervention. Cerebral computed tomography (CT), cervical and cerebral CT angiography (CTA), and cerebral CT perfusion (CTP) imaging may identify a subset of acute stroke patients without intracranial thrombus who may benefit from emergent CEA. Acute stroke patients underwent unenhanced brain CT imaging to exclude pathology that would contraindicate emergent therapy. Emergent CTAs of the intracranial and extracranial vessels were utilized to identify patients who presented with stroke symptoms based on the presence of isolated extracranial carotid disease in the absence of intracranial thromboembolism. CTP was then used to assess the extent of potentially reversible cerebral ischemia (penumbral tissue). Patients with isolated extracranial carotid lesions with significant reversible ischemia in the absence of large areas of irreversible cerebral damage underwent emergent CEA to salvage ischemic penumbra. In 1 year, 3 patients presented with large acute strokes in which CTA disclosed symptomatic extracranial internal carotid artery preocclusive or occlusive lesions without intracranial thromboembolic occlusions. CTP indicated a large area of ischemic penumbra with limited permanent injury. Mean age, time to presentation, and National Institutes of Health stroke score (NIHSS) were 66 years, 4.2 hr, and 19.3. All patients underwent emergent CEA with cervical carotid thrombectomy. Average time from stroke symptom onset to revascularization was 12.5 (range 5.9-19.0) hr. There were no perioperative deaths. At day 5, the mean NIHSS decreased to 7.6 and at day 30 was 4.7. The modified Rankin scale score dropped from a poststroke, preoperative level of 5 to 2.3 by day 30. Emergent CEA should be considered in patients presenting with large acute strokes based on favorable CT, CTA, and CTP findings. Emergent clot localization and physiological assessment of brain "tissue at risk" relative to irreversible cerebral infarction using CT, CTA, and CTP is now available. Utilization of this information by an experienced stroke team of neurologists, radiologists, and surgeons may aid in the recognition of a select group of patients in which emergent CEA may drive to improved outcomes.

A novel model of large vessel ischemic stroke in rabbits: microcatheter occlusion of the posterior cerebral artery

Background and purposeThe rabbit small clot embolic model for large vessel occlusion (LVO) is well established, yet has limitations. Blind introduction of autologous thrombus often fails to completely occlude a...

Abstract 3616: A Novel Model of Large Vessel Ischemic Stroke in New Zealand White Rabbits: Microcatheter Occlusion of the Posterior Cerebral Artery

Introduction: The rabbit small clot embolic model for large vessel occlusion (LVO) is well established, yet remains with limitations. Blind introduction of autologous thrombus often fails to occlude the target vessel, and when successful, the precise timing of occlusion and revascularization are difficult to control. Studies of cellular biology and neuroimaging of acute reversible cerebral ischemia (i.e., penumbral tissue) would benefit from a rabbit model in which LVO can be reliably induced and easily confirmed, where the time of occlusion and revascularization can be precisely controlled. Hypothesis: We hypothesized that microcatheterization of the posterior cerebral artery (PCA) in New Zealand white rabbits (NZWRs) would result in LVO, with time of revascularization controlled by microcatheter removal. We hypothesized that transient LVO would produce ischemia in subcortical structures supplied by the PCA (e.g., hippocampus), sparing the cortex, with longer duration LVO leading to irreversible cortical ischemia. Methods: Transfemoral 1.5F microcatheterization of the PCA was performed in anesthetized NZWRs using fluoroscopic guidance. LVO was maintained for 30 minutes (n=2), 60 minutes (n=2), 180 minutes (n=2) and 210 minutes (n=1), followed by microcatheter removal and reperfusion. Neuroimaging was obtained 3 hours later with MRI (3T DWI, FLAIR, gradient and perfusion sequences) and CT (64 slice noncontrast and perfusion imaging). Post-mortem histologic analysis of infarct was assessed using triphenyltetrazolium choloride (TTC) stain. Matched DWI and TTC sections were analyzed using ImageJ software. Results: Percent infarct of matched DWI and TTC sections was strongly correlated (r2 = 0.86). Transient LVO of 30-60 minutes resulted in infarction of the ipsilateral hippocampus and thalamus, sparing the cortex, while more prolonged LVO (180-210 minutes) led to cortical infarction as well. Conclusions: Image-guided microcatheter induction of LVO in NZW rabbits can reliably produce time-dependent infarction of cortical and subcortical structures, and thus may be a useful model for the study of penumbral cortical tissue.

White Matter Protection with Insulin-Like Growth Factor 1 and Hypothermia Is Not Additive after Severe Reversible Cerebral Ischemia in Term Fetal Sheep

Moderate cerebral hypothermia significantly improves survival without disability from perinatal hypoxia-ischemia. However, protection is partial. Insulin-like growth factor 1 (IGF-1) plays a key role in oligodendrocyte survival and myelination. The purpose of this study was to test the hypothesis that the combination of IGF-1 plus hypothermia could reduce postischemic white matter damage compared with hypothermia alone. Unanesthetized near-term fetal sheep received 30 min of cerebral ischemia, followed by either an infusion of 3 µg of IGF-1 intracerebroventricularly from 4.5 to 5.5 h plus cooling from 5.5 to 72 h (IGF-1 + hypothermia; n = 8), vehicle infusion plus cooling from 5.5 to 72 h (vehicle + hypothermia; n = 12), sham cooling plus sham infusion (ischemia control; n = 12) or sham ischemia (n = 5). The fetal extradural temperature was reduced from 39.4 ± 0.1°C to between 30 and 33°C. White matter was assessed after 5 days. Ischemia was associated with severe loss of CNPase-positive oligodendrocytes in white matter compared with sham ischemia (380 ± 138 vs. 1,180 ± 152 cells/field; mean ± SD; p < 0.001). Delayed hypothermia reduced cell loss (847 ± 297 cells/field, p < 0.01, vs. ischemia control), but there was no significant difference between vehicle + hypothermia and IGF-1 + hypothermia (1,015 ± 211 cells/field; NS). Ischemia was associated with increased caspase 3 expression in white matter (216 ± 41 vs. 19 ± 18 cells/field; p < 0.001). Hypothermia reduced numbers of activated caspase 3-positive cells (116 ± 81 cells/field; p < 0.05), with no significant difference between vehicle + hypothermia and IGF-1 + hypothermia (91 ± 27 cells/field; NS). In conclusion, delayed cotreatment with IGF-1 plus hypothermia after ischemia was associated with an improvement in white matter damage similar to that achieved by hypothermia alone.

Reversible Posterior Cerebral Artery Ischemia Related To Migraine With Aura

ABSTRACT Stroke can happen during migraine attack. If a stroke occurs during a typical migraine attack in a person, who is suffering from known migraine with aura, a correlation between migraine and stroke can be established. We are presenting clinical and radiologic findings of a patient who show clinical features of syncope and homonym hemianopsia together with migrenous headache and whose imaging findings suggest reversible posterior cerebral artery ischemia. Stroke associated with migraine is most commonly seen in posterior cerebral artery irrigation areas. Early treatment options can be presented to migraine patients with high stroke risk with the clarification of the correlation between migraine and ischemia. J. Exp. Clin. Med., 2011; 28:35-37

Decompressive craniectomy for acute stroke: early is better

Decompressive craniectomy for large, life-threatening supratentorial infarcts has been considered a controversial procedure for a long time. In the past 2 decades, authors of numerous single-center series have documented improved survival after decompressive craniectomy compared with maximal medical therapy.2 However, the procedure is not universally accepted. Detractors have been most vocal about the lack of Level A evidence and the danger that surgery could lead to a high proportion of survivors with severe disability. This controversy has sparked a few randomized clinical trials, and a landmark report of a pooled analysis of 3 such trials has answered some of the questions raised by critics.5 Among patients younger than 60 years old with a large middle cerebral artery infarct treated within 48 hours of stroke onset, the mortality rate decreased from 78% in the medically treated group to 29% in the decompressive craniectomy– treated group. This difference was statistically signifi cant. The authors of this report also concluded that 2 pa tients must be treated to prevent 1 death regardless of functional outcome. Four patients must be treated for each patient with a modified Rankin Scale score of 3 or less (a score most would agree corresponds to a decent quality of life). Despite these “high-quality” sci entific data and Level A evidence, several questions remain unanswered. In particular, is there a “neuroprotective” role for therapies (including decompressive cra niectomy) aimed at decreasing the secondary insult from vasogenic edema? In this issue of the Journal of Neurosurgery, Walberer and coworkers report their findings from an experimental model of reversible middle cerebral artery occlusion. These authors aimed to study the effects of vasogenic edema on infarct volume and func tional outcome. To eliminate the space-occupying ef fects of postinfarction edema, a bilateral decompressive craniectomy was prophylactically performed before reversible cerebral ischemia; the control group consisted of sham-operated animals. Infarct size was measured on MR images obtained 5 and 24 hours after ischemia on set. Ischemic lesions were consistently smaller in the craniectomy group at both the 5and 24-hour time points. Clinical scores were also significantly bet ter and the midline shift was less in rats that had un dergone prophylactic craniectomy. These observations lend further support to the notion that vasogenic edema aggravates the extent of infarction. Thus, therapies targeting vasogenic edema and its deleterious effects can prove neuroprotective. Hypothetically, vasogenic edema around the ischemic tissue causes regional compression of leptomeningeal vessels providing critical collateral blood flow to the penumbra. Indeed, experimental studies have suggested that decompressive craniectomy im proves cortical perfusion by increasing local cerebral blood flow through leptomeningeal collateral vessels.1 In the study by Walberer et al., animals were killed after 24 hours. Note, however, that postinfarction edema progresses well beyond that time point, and we don’t know for sure if the protective effect demonstrated in their ex perimental setting is maintained beyond 24 hours. An extension of this study might address this issue in the future. Can we use these observations to propose an ultraearly decompressive craniectomy and very aggressive intracranial pressure–targeted therapies in patients with acute cerebral infarction to improve functional out come? The easy answer is that randomized clinical trials are required. Experience shows that such trials are very difficult, expensive, and impractical to perform and often do not provide definitive answers. The decision to proceed with a decompressive craniectomy in a patient with a life-threatening infarct is always difficult because of the significance and impact (on the quality of life of the patient as well as the caregiver[s]) of the residual neu rological deficits. Nonetheless, when craniectomy is con sidered, data from the following and other studies3,4 sug gest that early is better.

Percutaneous transfemoral valvuloplasty of calcified and non-calcified aortic valves

Percutaneous transfemoral valvuloplasty was performed in 20 patients (aged 25-83 years; mean 62) with marked signs of aortic valve stenosis, some calcified, others noncalcified. The transvalvar systolic pressure gradient was reduced from a mean of 104 +/- 7 mm Hg to a mean of 46 +/- 4 mm Hg, the valvar opening area from 0.38 +/- 0.04 cm2 to 0.74 +/- 0.04 cm2. The result was judged to be unsatisfactory in four patients and required aortic valve replacement after initially good results from the balloon dilatation. Serious complications were reversible ventricular fibrillation and reversible cerebral ischemia with partial hemiparesis in one patient each. In three patients the femoral artery had to be repaired at the site of puncture, twice the balloon ruptured without sequelae, once reversible pericardial effusion occurred, and twice there were reactions to antibiotics given after the procedure. Invasive re-catheterizations were performed in four patients, at intervals of three months: no increase in pressure gradient was observed. The results indicate that reduction of the transvalvar pressure gradient by 40 mm Hg can produce rapid reversal of heart failure and a symptom-free state even in patients who were already decompensated.