Réza Behrouz

Re-exploring Tumor Necrosis Factor Alpha as a Target for Therapy in Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is a perplexing condition with high mortality and no treatment beyond supportive care. A major portion of the injurious process is takes place during the hours following the development of hematoma. This so-called secondary injury is characterized by an inflammatory cascade that involves a variety of cytokines, including tumor necrosis factor (TNF)-α. Several studies in the rodent model of ICH have shown a rapid increase in brain concentrations of TNF-α following hematoma induction. There is a reasonable body of evidence from experimental models of ICH suggesting that upregulation of TNF-α adjacent to the hematoma is associated with increased peri-hematomal edema, and that inhibition of TNF-α attenuates the formation and progression of this edema and ultimately improves outcomes. Unfortunately, efforts to expand upon these findings have interminably stalled at the pre-clinical phase. A robust clinical study to validate serum TNF-α as a marker for secondary injury in ICH patients is yet to materialize.

Small Vessel Cerebrovascular Disease: The Past, Present, and Future

Brain infarction due to small vessel cerebrovascular disease (SVCD)—also known as small vessel infarct (SVI) or “lacunar” stroke—accounts for 20% to 25% of all ischemic strokes. Historically, SVIs have been associated with a favorable short-term prognosis. However, studies over the years have demonstrated that SVCD/SVI is perhaps a more complex and less benign phenomenon than generally presumed. The currently employed diagnostic and therapeutic strategies are based upon historical and contemporary perceptions of SVCD/SVI. What is discovered in the future will unmask the true countenance of SVCD/SVI and help furnish more accurate prognostication schemes and effective treatments for this condition. This paper is an overview of SVCD/SVI with respect to the discoveries of the past, what is known now, and what will the ongoing investigations evince in the future.

Intravenous tenecteplase in acute ischemic stroke: an updated review

Tenecteplase in a genetically engineered variant of alteplase. Although the two have the same mechanism of action, tenecteplase has properties that makes it a seemingly more advantageous thrombolytic. Because of its rapid single-bolus administration, its use is favored over alteplase in the treatment of acute myocardial infarction. Over the past few years, several clinical studies have been conducted to assess the safety, feasibility, and efficacy of tenecteplase in ischemic stroke. In spite of the mixed results of these studies, experimentation with tenecteplase continues in from of clinical trials. In this article, the utility of tenecteplase in ischemic stroke will be discussed.

Prevention of Stroke in Rheumatoid Arthritis

The risk of cerebrovascular disease is increased among rheumatoid arthritis (RA) patients and remains an underserved area of medical need. Only a minor proportion of RA patients achieve suitable stroke prevention. Classical cardiovascular risk factors appear to be under-diagnosed and undertreated among patients with RA. Reducing the inflammatory burden is also necessary to lower the cardiovascular risk. An adequate control of disease activity and cerebrovascular risk assessment using national guidelines should be recommended for all patients with RA. For patients with a documented history of cerebrovascular or cardiovascular risk factors, smoking cessation and corticosteroids and non-steroidal anti-inflammatory drugs at the lowest dose possible are crucial. Risk score models should be adapted for patients with RA by introducing a 1.5 multiplication factor, and their results interpreted to appropriately direct clinical care. Statins, angiotensin-converting enzyme inhibitors, and angiotensin-II receptor blockers are preferred treatment options. Biologic and non-biologic disease-modifying anti-rheumatic drugs should be initiated early to mitigate the necessity of symptom control drugs and to achieve early alleviation of the inflammatory state. Early control can improve vascular compliance, decrease atherosclerosis, improve overall lipid and metabolic profiles, and reduce the incidence of heart disease that may lead to atrial fibrillation. In patients with significant cervical spine involvement, early intervention and improved disease control are necessary and may prevent further mechanical vascular injury.

Incidence, recurrence, and long-term survival of ischemic stroke subtypes: A population-based study in the Middle East

Background Incidence, risk factors, case fatality and survival rates of ischemic stroke subtypes are unknown in the Middle East due to the lack of community-based incidence stroke studies in this region. Aim To characterize ischemic stroke subtypes in a Middle Eastern population. Methods The Mashad Stroke Incidence Study is a community-based study that prospectively ascertained all cases of stroke among the 450,229 inhabitants of Mashhad, Iran between 2006 and 2007. We identified 512 cases of first-ever ischemic stroke [264 men (mean age 65.5 ± 14.4) and 248 women (mean age 64.14 ± 14.5)]. Subtypes of ischemic stroke were classified according to the TOAST criteria. Incidence rates were age standardized to the WHO and European populations. Results The proportion of stroke subtypes was distributed as follows: 14.1% large artery disease, 15% cardioembolic, 22.5% small artery disease, 43.9% undetermined and 4.5% other. The greatest overall incidence rates were attributed to undetermined infarction (49.97/100,000) followed by small artery disease (25.54/100,000). Prevalence of hypertension, diabetes and atrial fibrillation differed among ischemic stroke subtypes. Overall, there were 268 (52.34%) deaths and 73 (14.25%) recurrent strokes at five years after incident ischemic stroke, with the greatest risk of recurrence seen in the large artery disease (35.6%) and cardioembolic (35.5%) subgroups. Survival was similar in men and women for each stroke subtype. Conclusions We observed markedly greater incidence rates of ischemic stroke subtypes than in other countries within the Mashad Stroke Incidence Study after age standardization. Our findings should be considered when planning prevention and stroke care services in this region.

The risk of ischemic stroke in major rheumatic disorders

Rheumatic disorders (RD) are a range of conditions associated with inflammation of joints and connective tissue. They can manifest beyond the musculoskeletal system. Recent focus has been placed on the association of ischemic stroke with these conditions. Traditional vascular risk factors seem to be more prevalent in patients with certain types of RD than in the general population, but these factors do not fully explain the enhanced vascular risk in this population. Four major RD will be discussed in terms of their relationship with ischemic stroke: rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, and psoriatic arthritis.

Prior Cannabis Use Is Associated with Outcome after Intracerebral Hemorrhage

Objective: Recent evidence suggests that a potential harmful relationship exists between cannabis use and ischemic stroke. The purpose of this study was to determine the implications of cannabis use in intracerebral hemorrhage (ICH) patients. Methods: An analysis of an international, multicenter, observational database of consecutive patients with spontaneous ICH was conducted. We extracted the following characteristics on presentation: demographics, risk factors, antiplatelet or anticoagulant use, Glasgow Coma Scale, ICH score, neuroimaging parameters, and urine toxicology screen (UTS) results. Modified Rankin Scale (mRS) score was utilized for determination of outcome at discharge. Adjusted logistic ordinal regression was used as shift analysis to assess the impact of cannabis use on mRS score at discharge. The adjusted common OR measured the likelihood that cannabis use would lead to lower mRS scores. Results: Within a cohort of 725 spontaneous ICH patients, UTS was positive for cannabinoids in 8.6%. Cannabinoids-positive (CB+) patients were more frequently Caucasian (p < 0.001), younger (p < 0.001), and had lower median ICH scores on admission (p = 0.017) than those who were cannabinoids-negative. CB+ patients also showed a shift toward better outcome in the distribution of mRS categories, with an adjusted common OR of 0.544 (95% CI 0.330-0.895, p = 0.017). Conclusion: In this multinational cohort, cannabis use was discovered in nearly 10% of patients with spontaneous ICH. Although there was no relationship between cannabis use and specific ICH characteristics, CB+ patients had milder ICH presentation and less disability at discharge.

The Safety and Feasibility of Admitting Patients With Intracerebral Hemorrhage to the Step-Down Unit.

Background: Intracerebral hemorrhage (ICH) is a devastating and costly condition. Although the American Heart Association/American Stroke Association recommends admitting patients with ICH to a neurocritical care unit (NCCU), this strategy may accrue unnecessary cost for patients with relatively milder presentation. We conducted a prospective observational study to determine the safety and feasibility of admitting patients with mild ICH directly to a step-down unit (SDU) instead of an NCCU. Methods: Consecutive patients with “mild presentation,” defined as a combination of ICH score ≤2, National Institutes of Health Stroke Scale (NIHSS) ≤ 15, and Graeb score ≤2 (if intraventricular hemorrhage was present), were admitted to the SDU. Data were collected on age, gender as well as the initial NIHSS, Glasgow Coma Scale (GCS), ICH, and Graeb scores. Primary end point was any complication or death during hospital stay. Results: Twenty patients were admitted to the SDU. No patient was transferred to the NCCU from the SDU. One patient, who eventually died, had respiratory insufficiency due to hospital-acquired pneumonia. Conclusion: Admission of ICH patients with mild symptoms to the SDU is safe and feasible. Larger prospective studies are needed to define the specific criteria for admission.

Emerging Subspecialties in Neurology: Telestroke and teleneurology

In 2013, Dall et al.1 projected that by 2025, the societal need for neurologists will exceed availability by 19%. This number failed to account for the disproportionate number of neurologists practicing in urban and academic centers, likely underestimating the gap in rural populations. In a recent effort to improve access to neurologic services in these areas, telestroke and teleneurology networks have being championed as the solution. With the emergence of these networks come unique challenges and opportunities in the distribution and breadth of neurologic care that fellows and residents will need to understand to optimally incorporate this tool into their future practices.

Preoperative Cerebrovascular Evaluation in Patients With Infective Endocarditis

Approximately 12% to 40% of infective endocarditis patients experience cerebrovascular complications. One of the major clinical challenges in cerebrovascular medicine is management of infective endocarditis patients with cerebrovascular complications who require valve operations. Cerebrovascular specialists are often summoned to address appropriate preoperative brain imaging, timing of surgery, and estimation of the risk of perioperative cerebral embolization and hemorrhage. This article addresses these issues based on the available evidence.