Vishnumurthy Shushrutha Hedna

Hemispheric Differences in Ischemic Stroke: Is Left-Hemisphere Stroke More Common?

Background and Purpose Understanding the mechanisms underlying stroke can aid the development of therapies and improve the final outcome. The purposes of this study were to establish whether there are characteristic mechanistic differences in the frequency, severity, functional outcome, and mortality between left- and right-hemisphere ischemic stroke and, given the velocity differences in the carotid circulation and direct branching of the left common carotid artery from the aorta, whether large-vessel ischemia (including cardioembolism) is more common in the territory of the left middle cerebral artery. Methods Trial cohorts were combined into a data set of 476 samples. Using Trial of Org 10172 in Acute Stroke Treatment criteria, ischemic strokes in a total 317 patients were included in the analysis. Hemorrhagic stroke, stroke of undetermined etiology, cryptogenic stroke, and bilateral ischemic strokes were excluded. Laterality and vascular distribution were correlated with outcomes using a logistic regression model. The etiologies of the large-vessel strokes were atherosclerosis and cardioembolism. Results The overall event frequency, mortality, National Institutes of Health Stroke Scale (NIHSS) score, Glasgow Coma Scale score, and rate of mechanical thrombectomy interventions differed significantly between the hemispheres. Left-hemispheric strokes (54%) were more common than right-hemispheric strokes (46%; p=0.0073), and had higher admission NIHSS scores (p=0.011), increased mortality (p=0.0339), and higher endovascular intervention rates (p≤0.0001). ischemic strokes were more frequent in the distribution of the left middle cerebral artery (122 vs. 97; p=0.0003) due to the higher incidence of large-vessel ischemic stroke in this area (p=0.0011). Conclusions Left-hemispheric ischemic strokes appear to be more frequent and often have a worse outcome than their right-hemispheric counterparts. The incidence of large-vessel ischemic strokes is higher in the left middle cerebral artery distribution, contributing to these hemispheric differences. The hemispheric differences exhibit a nonsignificant trend when strokes in the middle cerebral artery distribution are excluded from the analysis.

Posterior reversible encephalopathy syndrome (PRES) and CT perfusion changes

Posterior reversible encephalopathy syndrome ( PRES) can present with focal neurologic deficits, mimicking a stroke and can often represent a diagnostic challenge when presenting atypically. A high degree of suspicion is required in the clinical setting in order to yield the diagnosis. Cerebral CT perfusion (CTP) is utilized in many institutions as the first line in acute stroke imaging. CTP has proved to be a very sensitive measure of cerebral blood flow dynamics, most commonly employed to delineate the infarcted tissue from penumbra (at-risk tissue) in ischemic strokes. But abnormal CTP is also seen in stroke mimics such as seizures, hypoglycemia, tumors, migraines and PRES. In this article we describe a case of PRES in an elderly bone marrow transplant recipient who presented with focal neurological deficits concerning for a cerebrovascular accident. CTP played a pivotal role in the diagnosis and initiation of appropriate management. We also briefly discuss the pathophysiology of PRES.

Vagus nerve stimulation in ischemic stroke: old wine in a new bottle.

Vagus nerve stimulation (VNS) is currently Food and Drug Administration-approved for treatment of both medically refractory partial-onset seizures and severe, recurrent refractory depression, which has failed to respond to medical interventions. Because of its ability to regulate mechanisms well-studied in neuroscience, such as norepinephrine and serotonin release, the vagus nerve may play an important role in regulating cerebral blood flow, edema, inflammation, glutamate excitotoxicity, and neurotrophic processes. There is strong evidence that these same processes are important in stroke pathophysiology. We reviewed the literature for the role of VNS in improving ischemic stroke outcomes by performing a systematic search for publications in Medline (1966–2014) with keywords “VNS AND stroke” in subject headings and key words with no language restrictions. Of the 73 publications retrieved, we identified 7 studies from 3 different research groups that met our final inclusion criteria of research studies addressing the role of VNS in ischemic stroke. Results from these studies suggest that VNS has promising efficacy in reducing stroke volume and attenuating neurological deficits in ischemic stroke models. Given the lack of success in Phase III trials for stroke neuroprotection, it is important to develop new therapies targeting different neuroprotective pathways. Further studies of the possible role of VNS, through normally physiologically active mechanisms, in ischemic stroke therapeutics should be conducted in both animal models and clinical studies. In addition, recent advent of a non-invasive, transcutaneous VNS could provide the potential for easier clinical translation.

Taming Glutamate Excitotoxicity: Strategic Pathway Modulation for Neuroprotection

Much work has been carried out in recent years showing that elevated glutamate levels in the extracellular environment of the central nervous system play a pivotal role in neurodegeneration in acute CNS injuries. With the elucidation of the mechanism governing glutamate excitotoxicity, researchers are devising therapeutic strategies to target different parts of the pathway which begins with glutamate accumulation and ultimately results in neuronal cell death. In this article, we review some of the major classes of agents that are currently being investigated and highlight some of the key studies for each. Glutamate scavenging is a relatively new approach that directly decreases glutamate levels in the brain, thus preventing excitotoxicity. Nitric oxide inhibitors and free radical scavengers are more well-studied strategies that continue to yield promising results.

Role of inflammatory markers in Takayasu arteritis disease monitoring

BackgroundTakayasu arteritis (TA) is an idiopathic large-vessel vasculitis that can result in significant morbidity and mortality secondary to progressive stenosis and occlusion. Monitoring disease progression is crucial to preventing relapse, but is often complicated by the lack of clinical symptoms in the setting of active disease. Although acute phase reactants such as ESR and CRP are generally used as an indicator of inflammation and disease activity, mounting evidence suggests that these markers cannot reliably distinguish active from inactive TA.Case presentationWe report a 24-year-old Hispanic female with a 5-year history of TA who presented with stroke-like symptoms and evidence of left MCA occlusion on imaging, despite a history of decreasing inflammatory markers. CTA revealed complete occlusion of the left common carotid artery, left subclavian, and left MCA from their origins. It also revealed a striking compensatory circulation supplying the left anterior circulation as well as the left subclavian as a response to progressive stenosis.ConclusionMonitoring ESR and CRP levels alone may not be a reliable method to evaluate disease progression in patients with TA, and should be taken in context with both patient’s clinical picture and the imaging. We recommend that serial imaging be performed regularly in the setting of active disease to monitor progression and allow for immediate therapy in response to evidence of disease advancement, with a relaxation of the imaging interval once the disease is presumed inactive.

Role of vasopressin and its antagonism in stroke related edema

Although many approaches have been tried in the attempt to reduce the devastating impact of stroke, tissue plasminogen activator for thromboembolic stroke is the only proved, effective acute stroke treatment to date. Vasopressin, an acute‐phase reactant, is released after brain injury and is partially responsible for the subsequent inflammatory response via activation of divergent pathways. Recently there has been increasing interest in vasopressin because it is implicated in inflammation, cerebral edema, increased intracerebral pressure, and cerebral ion and neurotransmitter dysfunctions after cerebral ischemia. Additionally, copeptin, a byproduct of vasopressin production, may serve as a promising independent marker of tissue damage and prognosis after stroke, thereby corroborating the role of vasopressin in acute brain injury. Thus, vasopressin antagonists have a potential role in early stroke intervention, an effect thought to be mediated via interactions with aquaporin receptors, specifically aquaporin‐4. Despite some ambiguity, vasopressin V1a receptor antagonism has been consistently associated with attenuated secondary brain injury and edema in experimental stroke models. The role of the vasopressin V2 receptor remains unclear, but perhaps it is involved in a positive feedback loop for vasopressin expression. Despite the encouraging initial findings we report here, future research is required to characterize further the utility of vasopressin antagonists in treatment of stroke.

Mechanisms of arm paresis in middle cerebral artery distribution stroke: Pilot study

The development of effective neurobiological adjuvants to rehabilitation of paresis caused by stroke will depend on understanding mechanisms of paresis. Our objective was to determine the extent to which upper-limb (UL) paresis after nonlacunar ischemic middle cerebral artery (MCA) distribution stroke is caused by infarction of posterior periventricular white matter (PVWM), where corticospinal fibers serving movement descend, and caused by infarction of the arm-hand region of precentral gyrus (ahPCG). We conducted a blinded, retrospective analysis of computed tomography and magnetic resonance imaging from a convenience sample of 64 prospectively evaluated subjects with UL paresis resulting from MCA distribution stroke. Of the subjects, 96.5% had PVWM involvement while 53% had minimal or no ahPCG involvement. Even in subjects with no UL function, 56% had very minimal infarction (<25%) of the ahPCG. Degree of paresis was statistically associated with presence or absence of detectable posterior PVWM damage but not with extent of ahPCG involvement. These preliminary findings suggest that posterior PVWM involvement may be a major, if not the principal, determinant of paresis in all hemispheric ischemic strokes and motivate further prospective studies of this problem.

Isolated middle cerebral artery dissection: a systematic review

Acute stroke can be missed in the emergency department, particularly in younger patients and in those with more vague symptoms such as headache or dizziness. Cervicocephalic dissections are one group of etiologies for acute stroke in the young. While cervicocephalic dissections are not uncommon in clinical practice, isolated middle cerebral artery dissection (MCAD) has been rarely reported as a cause for stroke. We sought to review the clinical implications and pathophysiology of an isolated MCAD. We searched the medical literature for isolated MCAD in clinical stroke patients using MEDLINE, HighWire, and Google Scholar databases from 1966 to 2013 using the keywords ‘middle cerebral artery dissection,’ ‘intracerebral artery dissection,’ and ‘middle cerebral artery dissection stroke.’ We reviewed cases to learn various characteristics of isolated MCAD. A total of 61 cases (62.3% male, mean age 44.16 ± 19.17 years) were reviewed from 54 publications. Most cases were reported from Asian countries (78.7%). Ischemic strokes were more common than hemorrhagic strokes (68.9%). Digital subtraction angiography was the most common imaging modality used to diagnose isolated MCAD (75.4%). Surgery was the preferred form of therapeutic intervention (39.3%). Males (n = 27/48, p = 0.0008) and those who presented with only ischemic syndromes (n = 22/48, p = 0.0009) had significantly higher rates of favorable outcome. Isolated MCAD is a rare disease that can contribute to the stroke burden of young patients. Further studies are needed to better characterize optimal treatment strategies and define outcomes for this rare condition.

Endothelin-1 Induced Middle Cerebral Artery Occlusion Model for Ischemic Stroke with Laser Doppler Flowmetry Guidance in Rat

Stroke is the number one cause of disability and third leading cause of death in the world, costing an estimated

Treatment of stroke related refractory brain edema using mixed vasopressin antagonism: a case report and review of the literature

70 billion in the United States in 2009. Several models of cerebral ischemia have been developed to mimic the human condition of stroke. It has been suggested that up to 80% of all strokes result from ischemic damage in the middle cerebral artery (MCA) area. In the early 1990s, endothelin-1 (ET-1) was used to induce ischemia by applying it directly adjacent to the surface of the MCA after craniotomy. Later, this model was modified by using a stereotaxic injection of ET-1 adjacent to the MCA to produce focal cerebral ischemia. The main advantages of this model include the ability to perform the procedure quickly, the ability to control artery constriction by altering the dose of ET-1 delivered, no need to manipulate the extracranial vessels supplying blood to the brain as well as gradual reperfusion rates that more closely mimics the reperfusion in humans. On the other hand, the ET-1 model has disadvantages that include the need for a craniotomy, as well as higher variability in stroke volume. This variability can be reduced with the use of laser Doppler flowmetry (LDF) to verify cerebral ischemia during ET-1 infusion. Factors that affect stroke variability include precision of infusion and the batch of the ET-1 used. Another important consideration is that although reperfusion is a common occurrence in human stroke, the duration of occlusion for ET-1 induced MCAO may not closely mimic that of human stroke where many patients have partial reperfusion over a period of hours to days following occlusion. This protocol will describe in detail the ET-1 induced MCAO model for ischemic stroke in rats. It will also draw attention to special considerations and potential drawbacks throughout the procedure.