The interface between stroke and infectious disease: infectious diseases leading to stroke and infections complicating stroke.

It is well established that several infectious diseases can directly lead to ischemic or hemorrhagic stroke during their course. It appears possible that common viral and bacterial infections can increase the susceptibility to stroke by promoting atherosclerosis, inflammation, and local thrombosis. Stroke commonly leads to disruption of protective mechanisms against infection and induces a cascade of anti-inflammatory and immunosuppressive reactions, which greatly increases the risk of infection. The social and economic costs of post-stroke infections and their impact on stroke morbidity and outcome are dramatic. Understanding the pathophysiologic links between stroke and infection is therefore of paramount importance, and effective preventive strategies to reduce the risk of infection are needed. This article summarizes current clinical and experimental data regarding the interactions between stroke and infection and outlines possible targets for therapeutic intervention.

Cervicocerebral arterial dissection.

Dissection of the cervicocerebral arteries is an infrequent occurrence but is a leading cause of stroke in young and otherwise healthy patients. A brief review of the history, pathogenesis, and management is presented. The proper management for stroke prevention in dissection is unclear as there have been no randomized, controlled trials performed; small trials are under way.

The promise and potential pitfalls of serum biomarkers for ischemic stroke and transient ischemic attack.

BACKGROUND: Ischemic stroke and transient ischemic attack can be difficult to diagnose clinically, and both acute and preventive therapies carry some risk. Serum biomarkers could increase diagnostic certainty by helping to distinguish cerebral ischemia from common mimics such as focal seizure, complicated migraine, and psychogenic spells. Biomarkers could also identify patients at high risk for future vascular events, which would aid in management decisions. REVIEW SUMMARY: There are many potential obstacles to finding these biomarkers, which are reviewed here, including the blood brain barrier, confounding by other conditions, and imperfect gold standards for use in validation. Diagnostic biomarkers are likely to be molecules found predominantly in brain tissue with rapid entry into the blood, whereas risk-stratification biomarkers may be related to the concept of an active atherosclerotic plaque. Many promising serum molecules have been examined in small series of patients with cerebrovascular disease. CONCLUSION: Large series examining many candidate molecules will be needed to find valid biomarkers, and this should be followed by use in future intervention trials to prove their utility.

Neuroprotection in cerebral ischemia: emphasis on the SAINT trial.

Acute ischemic stroke (AIS) is a significant cause of death and disability in the United States. It has been 10 years since tissue plasminogen activator became the first medication approved by the US Food and Drug Administration for treatment for AIS. However, this treatment simply reopens arteries. The identification of deleterious cellular reactions that occur secondary to cerebral ischemia has led investigators to search for neuroprotection strategies to complement reperfusion. More than 100 human trials, including a handful of phase III trials, had failed to produce an efficacious neuroprotective agent. In 2006, the first positive trial of neuroprotection was published: the SAINT I (Stroke-Acute Ischemic NXY Treatment) study. In February 2008, the SAINT II study was published, indicating that NXY-059 was not effective for AIS treatment.

Reliability of site-independent telemedicine when assessed by telemedicine-naive stroke practitioners.

INTRODUCTION: Telemedicine is used to assess patients with stroke remotely. The extent of training necessary to use these systems is unknown. A site-independent telemedicine system (used in the STRokE DOC trial) is reliable when used by telemedicine-trained investigators. We report a prospective evaluation of telemedicine's reliability when used by nontelemedicine-trained examiners. MATERIALS AND METHODS: In all, 25 patients with stroke were prospectively evaluated. Two team members (one bedside, one remote) simultaneously graded each patient using the National Institutes of Health Stroke Scale (NIHSS), modified NIHSS (mNIHSS), and modified Rankin scale. Patients followed commands of the remote telemedicine neurologist, who was untrained in, and had no experience with, telemedicine. RESULTS: Remote evaluations by telemedicine-naive examiners were feasible in 25 of 25 (100%) patients. One technical complication, which did not interfere with performing the examination, was noted. Median NIHSS score was 11.5. Average clinical examination took 13.9 minutes (improving from 22 to 8 minutes). Reliability was comparable with published studies, with 10/15 (67%) NIHSS and 9/11 (82%) mNIHSS items showing excellent agreement (Kappa > 0.75). Modified Rankin scale reliability was high (Kappa = 0.90). Spearman correlation (NIHSS and mNIHSS) for bedside examiner was 0.981 and for remote examiner was 0.966. DISCUSSION: It is reliable and valid for telemedicine-naive stroke examiners to assess clinical deficit and functional outcomes using a site-independent telemedicine system. Evaluation time decreased even with minimal telemedicine exposure. Further assessments should determine whether reliability persists with a larger pool of both untrained investigators and patients, and whether reliability improves with a dedicated training program.

Functional connectivity changes in the language network during stroke recovery.

OBJECTIVE: Several neuroimaging studies have examined language reorganization in stroke patients with aphasia. However, few studies have examined language reorganization in stroke patients without aphasia. Here, we investigated functional connectivity (FC) changes after stroke in the language network using resting-state fMRI and performance on a verbal fluency (VF) task in patients without clinically documented language deficits. METHODS: Early-stage ischemic stroke patients (N = 26) (average 5 days from onset), 14 of whom were tested at a later stage (average 4.5 months from onset), 26 age-matched healthy control subjects (HCs), and 12 patients with cerebrovascular risk factors (patients at risk, PR) participated in this study. We examined FC of the language network with 23 seed regions based on a previous study. We evaluated patients' behavioral performance on a VF task and correlation between brain resting-state FC (rsFC) and behavior. RESULTS: Compared to HCs, early stroke patients showed significantly decreased rsFC in the language network but no difference with respect to PR. Early stroke patients showed significant differences in performance on the VF task compared to HCs but not PR. Late-stage patients compared to HCs and PR showed no differences in brain rsFC in the language network and significantly stronger connections compared to early-stage patients. Behavioral differences persisted in the late stage compared to HCs. Change in specific connection strengths correlated with changes in behavior from early to late stage. CONCLUSIONS: These results show decreased rsFC in the language network and verbal fluency deficits in early stroke patients without clinically documented language deficits.

Potential biomarkers for the diagnosis of stroke.

Stroke is common, with a high rate of disability and death, and current therapies are both highly time sensitive and carry some risk, making rapid diagnosis important. Many cases of stroke are difficult to diagnose clinically during the acute phase, and there are limitations to the ability of diagnostic imaging to help with the necessary speed. A reliable and valid biomarker would be invaluable for this common clinical situation, as it has been with myocardial infarction. A large number of molecules have been evaluated for this role, both in the laboratory and in patients, but the results to date have been disappointing. In this article, we review the operative concepts in the search for a diagnostic biomarker of stroke, a few of the promising candidates and the current challenges to validation.