Inflammatory mechanisms in ischemic stroke: therapeutic approaches
Acute ischemic stroke is the third leading cause of death in industrialized countries and the most frequent cause of permanent disability in adults worldwide. Despite advances in the understanding of the pathophysiology of cerebral ischemia, therapeutic options remain limited. Only recombinant tissue-plasminogen activator (rt-PA) for thrombolysis is currently approved for use in the treatment of this devastating disease. However, its use is limited by its short therapeutic window (three hours), complications derived essentially from the risk of hemorrhage, and the potential damage from reperfusion/ischemic injury. Two important pathophysiological mechanisms involved during ischemic stroke are oxidative stress and inflammation. Brain tissue is not well equipped with antioxidant defenses, so reactive oxygen species and other free radicals/oxidants, released by inflammatory cells, threaten tissue viability in the vicinity of the ischemic core. This review will discuss the molecular aspects of oxidative stress and inflammation in ischemic stroke and potential therapeutic strategies that target neuroinflammation and the innate immune system. Currently, little is known about endogenous counterregulatory immune mechanisms. However, recent studies showing that regulatory T cells are major cerebroprotective immunomodulators after stroke suggest that targeting the endogenous adaptive immune response may offer novel promising neuroprotectant therapies.
Risk factors and outcomes for ischemic stroke.
Stroke continues to have a great impact on public health in the United States. Stroke is frequent, recurring, and is more often disabling than fatal. The annual incidence of new strokes in the United States is nearly one half million, with over 3 million stroke survivors alive today. Identifying risk factors for initial ischemic stroke, as well as characterizing the determinants of outcome (stroke recurrence and mortality) after ischemic stroke, is the basis for stroke prevention strategies. Modifiable and nonmodifiable risk factors for ischemic stroke have been identified and include age; gender; race/ethnicity; heredity; hypertension; cardiac disease, particularly atrial fibrillation; diabetes mellitus; hypercholesterolemia; cigarette smoking; and alcohol abuse. New risk factors, such as hypercoagulable states and patient foramen ovale, are currently being investigated. Follow-up studies have quantified case-fatality rates, early recurrence risk, and long-term mortality and recurrence risks. Despite advances in stroke prevention strategies and treatments, stroke recurrence is still the major threat to any stroke survivor. A major goal set by the Public Health Service in its National Health Promotion and Disease Prevention Objectives for the year 2000 is “to reduce stroke deaths to no more than 20 per 100,000.” Part of this can be achieved if the risk of stroke recurrence is reduced. However, the frequency and determinants of stroke recurrence are poorly understood. Data from epidemiologic studies can help identify risk factors and outcomes after ischemic stroke, as well as the selection of high-risk individuals for focused risk-factor modification. Current information on these topics is discussed.
Endovascular Treatment for Acute Ischemic Stroke
In patients with ischemic stroke, endovascular treatment results in a higher rate of recanalization of the affected cerebral artery than systemic intravenous thrombolytic therapy. However, comparison of the clinical efficacy of the two approaches is needed.
We randomly assigned 362 patients with acute ischemic stroke, within 4.5 hours after onset, to endovascular therapy (intraarterial thrombolysis with recombinant tissue plasminogen activator [t-PA], mechanical clot disruption or retrieval, or a combination of these approaches) or intravenous t-PA. Treatments were to be given as soon as possible after randomization. The primary outcome was survival free of disability (defined as a modified Rankin score of 0 or 1 on a scale of 0 to 6, with 0 indicating no symptoms, 1 no clinically significant disability despite symptoms, and 6 death) at 3 months.
A total of 181 patients were assigned to receive endovascular therapy, and 181 intravenous t-PA. The median time from stroke onset to the start of treatment was 3.75 hours for endovascular therapy and 2.75 hours for intravenous t-PA (P<0.001). At 3 months, 55 patients in the endovascular-therapy group (30.4%) and 63 in the intravenous t-PA group (34.8%) were alive without disability (odds ratio adjusted for age, sex, stroke severity, and atrial fibrillation status at baseline, 0.71; 95% confidence interval, 0.44 to 1.14; P=0.16). Fatal or nonfatal symptomatic intracranial hemorrhage within 7 days occurred in 6% of the patients in each group, and there were no significant differences between groups in the rates of other serious adverse events or the case fatality rate.
The results of this trial in patients with acute ischemic stroke indicate that endovascular therapy is not superior to standard treatment with intravenous t-PA.
Ischemic Stroke: A Complication of Tuberculous Meningitis
We report a case of a 45-year old Hispanic male who was diagnosed with tuberculous meningitis (TBM) presented to the emergency department (ED) with altered mental status, confusion, and violent behavior. Computed tomography (CT) scan of the head was normal and repeated lumbar puncture (LP) did not yield new findings. Magnetic resonance imaging (MRI) of head showed multiple ischemic infarcts. Non-tPA stroke protocol was followed and anti-TB medicines were continued. With continuous cardiac monitoring, echocardiogram (ECHO) was normal so arrhythmia was less likely. Soon he was more responsive and alert with no further episodes of agitation and behavioral changes. Then, he was able to walk with assistance and was discharged to acute rehabilitation facility.
Spinal Subarachnoid Hemorrhage Associated with Spinal Ischemic Stroke in the Thoracic Region of the Spinal Cord – A Case Report
We present a case report of a 69-year old man with spinal ischemic stroke and spinal subarachnoid hemorrhage (sSAH) in the thoracic region. The first complaint was low back pain, which was followed by retention of urine, inferior paraplegia and distal hypesthesia below Th7-8 dermatome. The diagnosis was confirmed by lumbar puncture, which showed xanthochromic cerebrospinal fluid with erythrocyte- and proteinrachia, and contrast MRI of thoracic region, the latter visualizing two lesions. The intraspinal lesion is hyperintense on Т2 and iso- to hypointense on Т1, corresponding to an ischemic spinal stroke. The extraspinal lesion is hypointense on all sequences and corresponds to a chronic sSAH. The patient denies traumatic injuries, but is with a history of a regular intake of Acenocumarol for chronic atrial fibrillation. The laboratory investigations at hospital admittance showed that the patient is in a state of hypocoagulability. The applied medications resulted in satisfactory improvement of the neurological symptoms.In our opinion the presented case report is of interest because of the extreme rarity of sSAH, moreover in association with spinal ischemic stroke. The hypocoagualability state is the most probable cause of sSAH, which is later complicated with arterial vasospasm, the latter resulting in spinal ischemic stroke.
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 Azharuddin, M., Lalani, I., Du, D. and Ghali, W., 2016. Ischemic stroke: A complication of tuberculous meningitis. International Neuropsychiatric Disease Journal, pp.1-6.
 Viteva, E. and Chaneva, O., 2016. Spinal Subarachnoid Hemorrhage Associated with Spinal Ischemic Stroke in the Thoracic Region of the Spinal Cord–A Case Report. International Neuropsychiatric Disease Journal, pp.1-5.