Prachi Mehndiratta

Current perspectives on the use of intravenous recombinant tissue plasminogen activator (tPA) for treatment of acute ischemic stroke

In 1995, the NINDS (National Institute of Neurological Disorders and Stroke) tPA (tissue plasminogen activator) Stroke Study Group published the results of a large multicenter clinical trial demonstrating efficacy of intravenous tPA by revealing a 30% relative risk reduction (absolute risk reduction 11%–15%) compared with placebo at 90 days in the likelihood of having minimal or no disability. Since approval in 1996, tPA remains the only drug treatment for acute ischemic stroke approved by the US Food and Drug Administration. Over the years, an abundance of research and clinical data has supported the safe and efficacious use of intravenous tPA in all eligible patients. Despite such supporting data, it remains substantially underutilized. Challenges to the utilization of tPA include narrow eligibility and treatment windows, risk of symptomatic intracerebral hemorrhage, perceived lack of efficacy in certain high-risk subgroups, and a limited pool of neurological and stroke expertise in the community. With recent US census data suggesting annual stroke incidence will more than double by 2050, better education and consensus among both the medical and lay public are necessary to optimize the use of tPA for all eligible stroke patients. Ongoing and future research should continue to improve upon the efficacy of tPA through more rapid stroke diagnosis and treatment, refinement of advanced neuroimaging and stroke biomarkers, and successful demonstration of alternative means of reperfusion.

Stroke in Asia: geographical variations and temporal trends

Asian countries are in various stages of epidemiological transition and therefore exhibit a great diversity in disease patterns. Collectively, they comprise almost two-third of the worlds total mortality due to stroke. The purpose of this review is to explore existing epidemiological data on stroke, highlight the temporal trends in stroke epidemiology in various regions of Asia and predict future patterns based on these observations. Our search revealed that there is a lack of good epidemiological data from most Asian countries. Whatever data exist are not comparable due to lack of standardised methodology for ascertaining stroke and its subtypes. For this and other reasons, these estimates exhibit country-to-country variation and also within-country variability. We have also reviewed temporal trends in stroke incidence and prevalence in 12 Asian countries and the evolution of stroke subtypes over the past two decades. Important observations include a rise in stroke incidence in most Asian countries, an earlier age at onset compared with the West, a relative increase in the proportion of ischaemic strokes and a decline in haemorrhagic strokes. Among ischaemic stroke subtypes, lacunar strokes, which were once the commonest variety, are now declining. Emerging data suggest that large artery atherosclerosis and in particular that of intracranial vessels is the predominant aetiology in most Asian countries. The review also identified important gender differences in terms of stroke risk factors, prevalence and outcomes. There is need for sound epidemiological data from most countries to understand the disease better and plan policy-level interventions to decrease the burden. We identify a need for standard format or guidelines for conducting stroke epidemiological studies especially in developing Asian countries. This region must be identified as a priority region for stroke-related interventions and preventive strategies by global healthcare authorities and organisations.

Human prion diseases: surgical lessons learned from iatrogenic prion transmission

The human prion diseases, or transmissible spongiform encephalopathies, have captivated our imaginations since their discovery in the Fore linguistic group in Papua New Guinea in the 1950s. The mysterious and poorly understood infectious protein has become somewhat of a household name in many regions across the globe. From bovine spongiform encephalopathy (BSE), commonly identified as mad cow disease, to endocannibalism, media outlets have capitalized on these devastatingly fatal neurological conditions. Interestingly, since their discovery, there have been more than 492 incidents of iatrogenic transmission of prion diseases, largely resulting from prion-contaminated growth hormone and dura mater grafts. Although fewer than 9 cases of probable iatrogenic neurosurgical cases of Creutzfeldt-Jakob disease (CJD) have been reported worldwide, the likelihood of some missed cases and the potential for prion transmission by neurosurgery create considerable concern. Laboratory studies indicate that standard decontamination and sterilization procedures may be insufficient to completely remove infectivity from prion-contaminated instruments. In this unfortunate event, the instruments may transmit the prion disease to others. Much caution therefore should be taken in the absence of strong evidence against the presence of a prion disease in a neurosurgical patient. While the Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) have devised risk assessment and decontamination protocols for the prevention of iatrogenic transmission of the prion diseases, incidents of possible exposure to prions have unfortunately occurred in the United States. In this article, the authors outline the historical discoveries that led from kuru to the identification and isolation of the pathological prion proteins in addition to providing a brief description of human prion diseases and iatrogenic forms of CJD, a brief history of prion disease nosocomial transmission, and a summary of the CDC and WHO guidelines for prevention of prion disease transmission and decontamination of prion-contaminated neurosurgical instruments.

Prevalence of dural venous sinus stenosis and hypoplasia in a generalized population

Background and purpose While recent literature has described the prevalence of transverse sinus stenosis in patients with idiopathic intracranial hypertension, tinnitus, and refractory headaches, it is unclear what the prevalence is in the general population. This study evaluates the prevalence of venous sinus stenosis and hypoplasia in the general patient population. Materials and methods 355 of 600 consecutive patients who underwent CT angiography of the head met the inclusion criteria. The diameters of the dural venous sinuses were recorded. Each study was evaluated by a neuroradiologist for the presence of stenoses. Univariate and multivariate statistical analyses were performed by a statistician. Results The prevalence of unilateral transverse sinus stenosis or hypoplasia in a sample of patients representing the general population was 33%, the prevalence of bilateral transverse sinus stenosis was 5%, and the prevalence of unilateral stenosis with contralateral hypoplasia was 1%. A multivariate analysis identified arachnoid granulations as a predictor of stenosis (p<0.001). Gender trended toward significance (p=0.094). Race was not a significant predictor of stenosis (p=0.745). Conclusions The prevalence of bilateral transverse sinus stenosis in the general population is not trivial. These data may be used as a reference for understanding the mechanistic role of stenoses in idiopathic intracranial hypertension, tinnitus, and refractory headaches.

Shared genetic susceptibility of vascular-related biomarkers with ischemic and recurrent stroke

Objective: To investigate the genetic contributors to cerebrovascular disease and variation in biomarkers of ischemic stroke. Methods: The Vitamin Intervention for Stroke Prevention Trial (VISP) was a randomized, controlled clinical trial of B vitamin supplementation to prevent recurrent stroke, myocardial infarction, or death. VISP collected baseline measures of C-reactive protein (CRP), fibrinogen, creatinine, prothrombin fragments F1+2, thrombin-antithrombin complex, and thrombomodulin prior to treatment initiation. Genome-wide association scans were conducted for these traits and follow-up replication analyses were performed. Results: We detected an association between CRP single nucleotide polymorphisms (SNPs) and circulating CRP levels (most associated SNP, rs2592902, p = 1.14 × 10−9) in 2,100 VISP participants. We discovered a novel association for CRP level in the AKR1D1 locus (rs2589998, p = 7.3 × 10−8, approaching genome-wide significance) that also is an expression quantitative trait locus for CRP gene expression. We replicated previously identified associations of fibrinogen with SNPs in the FGB and LEPR loci. CRP-associated SNPs and CRP levels were significantly associated with risk of ischemic stroke and recurrent stroke in VISP as well as specific stroke subtypes in METASTROKE. Fibrinogen levels but not fibrinogen-associated SNPs were also found to be associated with recurrent stroke in VISP. Conclusions: Our data identify a genetic contribution to inflammatory and hemostatic biomarkers in a stroke population. Additionally, our results suggest shared genetic contributions to circulating CRP levels measured poststroke and risk for incident and recurrent ischemic stroke. These data broaden our understanding of genetic contributors to biomarker variation and ischemic stroke risk, which should be useful in clinical risk evaluation.

Poliomyelitis: Historical Facts, Epidemiology, and Current Challenges in Eradication

Poliomyelitis is a highly infectious disease caused by a virus belonging to the Picornaviridae family. It finds a mention even in ancient Egyptian paintings and carvings. The clinical features are varied ranging from mild cases of respiratory illness, gastroenteritis, and malaise to severe forms of paralysis. These have been categorized into inapparent infection without symptoms, mild illness (abortive poliomyelitis), aseptic meningitis (nonparalytic poliomyelitis), and paralytic poliomyelitis. This disease has been associated with crippling deformities affecting thousands of lives throughout the world. Only due to the perseverance and determination of great scientists in 1900s, the genomic structure of the virus and its pathogenesis could be elucidated. Contribution of Salk and Sabin in the form of vaccines-oral polio vaccine (OPV) and the inactivated polio vaccine-heralded a scientific revolution. In 1994, the World Health Organization (WHO) Region of The Americas was certified polio free followed by the WHO Western Pacific Region in 2000 and the WHO European Region in June 2002 of the 3 types of wild poliovirus (types 1, 2, and 3). In 2013, only 3 countries remained polio endemic-Nigeria, Pakistan, and Afghanistan. Global eradication of polio is imperative else the threat of an outbreak will hover forever. Today, all the governments of the world in collaboration with WHO stand unified in their fight against poliomyelitis and the task when achieved will pave the way for eliminating other infections in future.

Etiologic Stroke Subtypes: Updated Definition and Efficient Workup Strategies

Opinion statementStroke affects approximately 16.9 million individuals per year worldwide and is the second leading cause of death. Stroke represents a family of related, but distinct subtypes. Classifying stroke subtypes must take into account various aspects of a standardized stroke workup to allow optimization of treatment and prevention strategies. Secondary prevention and pharmacologic treatment is tailored based on stroke mechanism. Additionally prognostication and recurrent risk also depends on stroke etiology. Efficient workup of stroke relies on a thorough history, clinical examination, imaging studies, and putative mechanism of stroke that lead the treating physician to a particular etiological path. Here , we provide the reader with updated definitions of etiologic ischemic stroke types as well as efficient workup strategies.

Screening individuals with intracranial aneurysms for abdominal aortic aneurysms is cost-effective based on estimated coprevalence

OBJECTIVEnAneurysm rupture is a major cause of morbidity and mortality, and evidence suggests shared risk for both abdominal aortic aneurysms (AAAs) and intracranial aneurysms (IAs). We hypothesized that screening for AAA in patients with known IA is cost-effective.nnnMETHODSnWe used a decision tree model to compare costs and outcomes of AAA screening vs no screening in a hypothetical cohort of patients with IA. We measured expected outcomes using quality-adjusted life-years (QALYs) and the incremental cost-effectiveness ratio (ICER). We performed a Monte Carlo simulation and additional sensitivity analyses to assess the effects of ranging base case variables on model outcomes and identified thresholds where a decision alternative dominated the model (both less expensive and more effective than the alternative).nnnRESULTSnIn our base case analysis, screening for AAA provided an additional 0.17 QALY (2.5-97.5 percentile: 0.11-0.27 QALY) at a saving of

Seizures in Cerebral Venous Sinus Thrombosis

201 (2.5-97.5 percentile:

Seizures in Arteriovenous Malformations

-127 to