Carotid atherosclerotic disease: A systematic review of pathogenesis and management.

Carotid stenosis is an important contributor to ischemic stroke risk with resultant significant impact on neurological disability and death in adults and with worldwide implications. Management of carotid stenosis is impacted by whether there are associated symptoms along with the degree of stenosis. Understanding of the pathogenesis of carotid atherosclerosis or stenosis is important in management of carotid stenosis. Atherosclerotic plaque formation is a chronic insidious process with a number of potential contributors to the formation of such a plaque. The definition of atherosclerosis is not simply limited to abnormal deposition of lipid but also includes a chronic, complex, inflammatory process. Molecularly, in atherosclerosis, there is decreasing nitric oxide (NO) bioavailability, activity and/or expression of endothelial NO synthase, or increasing degradation of NO secondary to enhanced superoxide production. These above changes cause endothelial dysfunction leading to formation of foam cell followed by formation on lipid plaque. After lipid plaque formation, stable or unstable atherosclerotic plaque is formed depending on the calcium deposition over the lipid plaque. It continues to be clearly established that carotid intervention for symptomatic high-grade carotid stenosis is best managed with intervention either by carotid endarterectomy or carotid stenting. However, asymptomatic carotid stenosis is the subject of considerable controversy in terms of optimal management. This review of carotid atherosclerosis is an attempt to incorporate the information provided by more recent studies on pathogenesis and management which may help in the decision-making process for optimal management for protection against stroke.

EDITORIAL: Stroke-Pathophysiology and New Therapeutic Strategies.

This Special Issue of Biomedicines highlights recent advances in stroke evaluation and management and provides some pertinent information about potential new directions of stroke intervention in the research realm [...].

The Spectrum of Acute Cerebrovascular Disease in Patients with COVID-19.

(1) Background: COVID-19 infection is responsible for the ongoing pandemic and acute cerebrovascular disease (CVD) has been observed in COVID-19 patients. (2) Methods: We conducted a retrospective, observational study of hospitalized adult patients admitted to our hospital with SARS-CoV-2 and acute cerebrovascular disease. All clinical data were reviewed including epidemiology, clinical features, laboratory data, neuroradiological findings, hospital management and course from 32 patients hospitalized for COVID-19 management with acute cerebrovascular disease. (3) Results: Acute CVD with COVID-19 was associated with higher NIH stroke scale on discharge compared to non-COVID-19 CVDs. Seizures complicated the hospital course in 16% of COVID-19 patients with CVD. The majority of the acute CVDs were ischemic (81%) in nature followed by hemorrhagic (22%). Acute CVD with COVID-19 resulted in average hospital stays greater than twice that of the control group (13 days in COVID-19, 5 days in control). Acute CVD with COVID-19 patients had worse clinical outcomes with 31% patient deaths and 6% discharged to hospice. In the control group, 6% of patients died. (4) Conclusions: Acute CVD associated with COVID-19 tends to be more complicated with unique and adverse clinical phenotype, longer hospital admissions, and worse clinical outcomes.

Heart-Brain Relationship in Stroke.

The patient presenting with stroke often has cardiac-related risk factors which may be involved in the mechanism of the stroke. The diagnostic assessment is predicated on recognition of this potential relationship. Naturally, an accurate history is of utmost importance in discerning a possible cause and effect relationship. The EKG is obviously an important clue as well as it allows immediate assessment for possible cardiac arrhythmia, such as atrial fibrillation, for possible acute ischemic changes reflective of myocardial ischemia, or there may be indirect factors such as the presence of left ventricular hypertrophy, typically seen with longstanding hypertension, which could be indicative of a hypertensive mechanism for a patient presenting with intracerebral hemorrhage. For all presentations in the emergency room, the vital signs are important. An elevated body temperature in a patient presenting with acute stroke raises concern about possible infective endocarditis. An irregular-irregular pulse is an indicator of atrial fibrillation. A markedly elevated blood pressure is not uncommon in both the acute ischemic and acute hemorrhagic stroke setting. One tends to focus on possible cardioembolic stroke if there is the sudden onset of maximum neurological deficit versus the stepwise progression more characteristic of thrombotic stroke. Because of the more sudden loss of vascular supply with embolic occlusion, seizure or syncope at onset tends to be supportive of this mechanism. Different vascular territory involvement on neuroimaging is also a potential indicator of cardioembolic stroke. Identification of a cardiogenic source of embolus in such a setting certainly elevates this mechanism in the differential. There have been major advances in management of acute cerebrovascular disease in recent decades, such as thrombolytic therapy and endovascular thrombectomy, which have somewhat paralleled the advances made in cardiovascular disease. Unfortunately, the successful limitation of myocardial damage in acute coronary syndrome, with intervention, does not necessarily mirror a similar salutary effect on functional outcome with cerebral infarction. The heart can also affect the brain from a cerebral perfusion standpoint. Transient arrhythmias can result in syncope, while cardiac arrest can result in hypoxic-ischemic encephalopathy. Cardiogenic dementia has been identified as a mechanism of cognitive impairment associated with severe cardiac failure. Structural cardiac abnormalities can also play a role in brain insult, and this can include tumors, such as atrial myxoma, patent foramen ovale, with the potential for paradoxical cerebral embolism, and cardiomyopathies, such as Takotsubo, can be associated with precipitous cardioembolic events.

Antithrombotic Therapy in the Prevention of Stroke.

OVERVIEW: Ischemic stroke is a leading cause of death and disability throughout the world. Antithrombotic therapy, which includes both antiplatelet and anticoagulant agents, is a primary medication of choice for the secondary prevention of stroke. However, the choices vary with the need to incorporate evolving, newer information into the clinical scenario. There is also the need to factor in co-morbid medical conditions as well as the cost ramifications for a particular patient as well as compliance with the regimen. Pertinent Updates: In the acute setting, dual antiplatelet therapy from three weeks to up to three months has become recognized as a reasonable approach for patients with either minor stroke or transient ischemic attack or those with symptoms associated with higher-grade intracranial stenosis. This approach is favored for non-cardioembolic stroke as a cardiogenic mechanism tends to be best managed with attention to the cardiac condition as well as anticoagulant therapy. Risk stratification for recurrent stroke is important in weighing potential risk versus benefits. For example, prolonged dual antiplatelet therapy, with a combination such as aspirin and clopidogrel or aspirin and ticagrelor, tends to have negation of the potential clinical benefit of stroke prevention, over time, by the enhanced bleeding risk. Anticoagulant choices are now impacted by newer agents, initially identified as novel oral anticoagulants (NOACs), which also became associated with "non-vitamin K" agents as they are no longer considered novel. Alternatively, they are now often identified as direct oral anticoagulants (DOACs). They tend to be viewed as superior or non-inferior to warfarin with the caveat that warfarin is still viewed as the agent of choice for stroke prevention in patients with mechanical heart valves. CONCLUSION: Based upon cumulative information from multiple clinical trials of secondary prevention of stroke, there is an increasing array of approaches in an effort to provide optimal management. Antithrombotic therapy, including in combination with anticoagulant therapy, continues to evolve with the general caveat that "one size does not fit all". In view of this, we desire to provide an evidence-based approach for the prevention of stroke with antithrombotic agents.

The Role of the ACE2/MasR Axis in Ischemic Stroke: New Insights for Therapy.

Ischemic stroke remains the leading cause of neurologically based morbidity and mortality. Current stroke treatment is limited to two classes of FDA-approved drugs: thrombolytic agents (tissue plasminogen activator (tPA)) and antithrombotic agents (aspirin and heparin), which have a narrow time-window (<4.5 h) for administration after onset of stroke symptoms. While thrombolytic agents restore perfusion, they carry serious risks for hemorrhage, and do not influence damage responses during reperfusion. Consequently, stroke therapies that can suppress deleterious effects of ischemic injury are desperately needed. Angiotensin converting enzyme-2 (ACE2) has been recently suggested to beneficially influence experimental stroke outcomes by converting the vasoconstrictor Ang II into the vasodilator Ang 1-7. In this review, we extensively discuss the protective functions of ACE2-Ang (1-7)-MasR axis of renin angiotensin system (RAS) in ischemic stroke.

Overview of Acute Ischemic Stroke Evaluation and Management.

Stroke is a major contributor to death and disability worldwide. Prior to modern therapy, post-stroke mortality was approximately 10% in the acute period, with nearly one-half of the patients developing moderate-to-severe disability. The most fundamental aspect of acute stroke management is "time is brain". In acute ischemic stroke, the primary therapeutic goal of reperfusion therapy, including intravenous recombinant tissue plasminogen activator (IV TPA) and/or endovascular thrombectomy, is the rapid restoration of cerebral blood flow to the salvageable ischemic brain tissue at risk for cerebral infarction. Several landmark endovascular thrombectomy trials were found to be of benefit in select patients with acute stroke caused by occlusion of the proximal anterior circulation, which has led to a paradigm shift in the management of acute ischemic strokes. In this modern era of acute stroke care, more patients will survive with varying degrees of disability post-stroke. A comprehensive stroke rehabilitation program is critical to optimize post-stroke outcomes. Understanding the natural history of stroke recovery, and adapting a multidisciplinary approach, will lead to improved chances for successful rehabilitation. In this article, we provide an overview on the evaluation and the current advances in the management of acute ischemic stroke, starting in the prehospital setting and in the emergency department, followed by post-acute stroke hospital management and rehabilitation.

Emerging Concepts in Vascular Dementia: A Review.

OBJECTIVE: Vascular dementia (VaD) is the second most common cause of dementia and a major health concern worldwide. A comprehensive review on VaD is warranted for better understanding and guidance for the practitioner. We provide an updated overview of the epidemiology, pathophysiological mechanisms, neuroimaging patterns as well as current diagnostic and therapeutic approaches. MATERIALS AND METHODS: A narrative review of current literature in VaD was performed based on publications from the database of PubMed, Scopus and Google Scholar up to January, 2021. RESULTS: VaD can be the result of ischemic or hemorrhagic tissue injury in a particular region of the brain which translates into clinically significant cognitive impairment. For example, a cerebral infarct in the speech area of the dominant hemisphere would translate into clinically significant impairment as would involvement of projection pathways such as the arcuate fasciculus. Specific involvement of the angular gyrus of the dominant hemisphere, with resultant Gerstman's syndrome, could have a pronounced effect on functional ability despite being termed a "minor stroke". Small vessel cerebrovascular disease can have a cumulate effect on cognitive function over time. It is unfortunately well recognized that "good" functional recovery in acute ischemic or haemorrhagic stroke, including subarachnoid haemorrhage, does not necessarily translate into good cognitive recovery. The victim may often be left unable to have gainful employment, drive a car safely or handle their affairs independently. CONCLUSIONS: This review should serve as a compendium of updated information on VaD and provide guidance in terms of newer diagnostic and potential therapeutic approaches.

Human placenta mesenchymal stem cell protection in ischemic stroke is angiotensin converting enzyme-2 and masR receptor-dependent.

Thromboembolic stroke remains a major cause of neurological disability and death. Current stroke treatments (aspirin, tissue plasminogen activator) are significantly limited by timing and risks for hemorrhage which have driven researchers to explore other approaches. Stem cell-based therapy appears to be an effective option for ischemic stroke. Besides trans-differentiation into neural cells, stem cells also provide acute protection via paracrine signaling pathways through which releasing neuroprotective factors. We previously reported that intraperitoneal administration of human placenta mesenchymal stem cell (hPMSC) therapy upon reperfusion significantly protected the brain against middle cerebral artery occlusion (MCAO)-induced injury. In the present study, we specifically investigated the role of hPMSC-derived angiotensin converting enzyme-2 (ACE-2) in protection of MCAO-induced brain injury by measurement of brain tissue viability, cerebral blood flow, and neurological score. Here, we report for the first time that hPMSC expressing substantial amount of ACE-2, which mediates hPMSC protection in the MCAO model. Strikingly, we found that the protective effects of hPMSC in MCAO-induced brain injury could be attenuated by pretreatment of hPMSCs with MLN-4760, a specific inhibitor of ACE-2 activity, or by transfection of hPMSCs with ACE-2-shRNA-lentivirus. The hPMSC-derived ACE-2 specific protective mechanism was further demonstrated by administration of PD123319, an Angiotensin type-2 receptor antagonist, or A779, a MasR antagonist. Importantly, our study demonstrated that the protective effects of hPMSC in experimental stroke are ACE-2/MasR dependent and this signaling pathway represents an innovative and highly promising approach for targeted stroke therapy.

Neurological complications of syncope and sudden cardiac arrest.

Syncope is very common and usually comes with enough warning for the person to assume a safer position rather than fall in a potentially dangerous way. Syncope may be associated with pregnancy, for example, but we rarely encounter significant injury related to the potential for an associated fall. In the elderly, however, there are often comorbid factors such as delayed reaction time and other aspects of cognitive impairment, along with gait instability, that can affect the defensive reflexes to the point that brain injury, including subdural or epidural hematoma, is not uncommonly encountered. Sudden syncope without warning can also have both neurological and general physical implications in terms of driving safety, safety operating potentially dangerous equipment or exposure to heights as well as the potential impact for drowning or near-drowning while swimming or taking a bath. Sudden death, from whatever the mechanism, implies cerebral hypoperfusion with the potential consequences of hypoxic-ischemic brain injury.

Utilization of the large-bore Penumbra JET 7 reperfusion catheter in thrombectomy for acute ischemic stroke: A single-center experience.

BACKGROUND AND PURPOSE: The Penumbra JET 7 reperfusion catheter is used in the revascularization of large vessel occlusions in acute ischemic stroke. Description of its use in clinical practice remains limited. Our purpose is to describe our initial experience with the Penumbra JET 7 reperfusion catheter and to report on its safety and efficacy in different thrombectomy techniques. MATERIALS AND METHODS: We conducted a retrospective study of 50 patients treated with thrombectomy using the Penumbra JET 7 reperfusion catheter. Mean patient age and admission National Institutes of Health Stroke Scale were 70.6 and 17.76, respectively. The most common sites of vessel occlusion were the M1 segment (72%) followed by distal internal carotid artery (14%). Thrombectomy was performed using the direct aspiration first-pass technique and/or aspiration in conjunction with a stent retriever. RESULTS: Revascularization was achieved in a total of 44 cases (88%). Successful navigation of the Penumbra JET 7 reperfusion catheter to the occlusion site with clot engagement was achieved in 94% of cases. Mean time from vascular access to revascularization was 31.60 min. No catheter-related complications occurred. Clinical outcome data were collected from 43 patients (86%). Of those patients, 51% achieved good outcome (modified Rankin score of 0-2) at 60 or more days follow-up, 28% had poor outcome (modified Rankin score of 3-5), and 9 patients died (21%). CONCLUSION: The use of the Penumbra JET 7 reperfusion catheter for treatment of acute ischemic stroke was observed to be safe and effective with appropriate revascularization outcomes in different thrombectomy techniques.

Implications of the use of mechanical thrombectomy on outcome in large vessel occlusion following the 2015 landmark trials.

BACKGROUND: The effectiveness of mechanical thrombectomy (MT) was demonstrated in five landmark trials published in2015.Mechanical thrombectomy is now standard of care for acute ischemic stroke and has been growing in popularity after publication of landmark trials. OBJECTIVE: To analyze outcomes and trends of the use of MT and intravenous thrombolysis (IVT) in patients with acute ischemic stroke in US hospitals before and after publication of these trials. METHODS: Patients discharged with a diagnosis of ischemic stroke between 2012 to 2017 were diagnosed using ICD codes from the National Inpatient Sample. Thereafter, patients given acute stroke treatment were identified using the corresponding procedure codes for IVT and MT. The primary clinical outcomes of in-hospital mortality and disability were then compared between two time periods: 2012-2014 (pre-landmark trials) and 2015-2017 (post-landmark trials). Binary logistic regression and Χ2 tests were used for statistical analysis. RESULTS: A total of 57 675 patients (median age 68.9 years (range 18-90), 50.1% female) were identified with acute procedures. Of these patients, 57.6% were from the post-landmark trials time period. Despite an increased number of cases, the rate of IVT decreased from 84.3% to 75.9% and the rate of IVT+MT decreased from 7.1% to 6.3%. After publication of the pivotal trials in 2015, the rates of MT increased from 8.7% to 17.8%. Significant reductions of in-hospital mortality (7.1% vs 8.7%, p<0.001) and disability (64% vs 66.2%, p<0.001) were noted. CONCLUSION: The analysis showed a significant increase in the proportion of patients receiving MT after 2015. This has translated into reduction of in-hospital mortality and improvement in disability.

Human placental mesenchymal stem cells improve stroke outcomes via extracellular vesicles-mediated preservation of cerebral blood flow.

BACKGROUND: Besides long-term trans-differentiation into neural cells, benefits of stem cell therapy (SCT) in ischemic stroke may include secretion of protective factors, which partly reflects extracellular vesicle (EVs) released by stem cell. However, the mechanism(s) by which stem cells/EVs limit stroke injury have yet to be fully defined. METHODS: We evaluated the protection effect of human placenta mesenchymal stem cells (hPMSC) as a potential form of SCT in experimental ischemic stroke 'transient middle cerebral artery occusion (MCAO)/reperfusion' mice model. FINDINGS: We found for the first time that intraperitoneal administration of hPMSCs or intravenous hPMSC-derived EVs, given at the time of reperfusion, significantly protected the ipsilateral hemisphere from ischemic injury. This protection was associated with significant restoration of normal blood flow to the post-MCAO brain. More importantly, EVs derived from hPMSC promote paracrine-based protection of SCT in the MCAO model in a cholesterol/lipid-dependent manner. INTERPRETATION: Together, our results demonstrated beneficial effects of hPMSC/EVs in experimental stroke models which could permit the rapid "translation" of these cells into clinical trials in the near-term.

Evolving Approaches to Antithrombotics in Stroke Prevention and Treatment.

The optimization of antithrombotic therapy for acute stroke treatment and secondary prevention is an evolving process based on an increasing array of studies that provide an evidence-based approach. Options have increased dramatically with the release of the non-vitamin K oral anticoagulants and with the results of recent randomized clinical trials designed to assess potential benefits versus risks for patients in an individualized fashion. Recent studies have provided important information to guide choice and dosing of antiplatelet agents as well as the length of treatment. Anticoagulant use is particularly pertinent for stroke prevention in patients at higher risk of atrial fibrillation and may have a place in certain other stroke mechanisms. One important focus of study is the potential benefit of combined antiplatelet and anticoagulant therapy. Options for our patients, when the initial choice of therapy does not demonstrate benefit or is not well tolerated, clearly, are valuable. For example, short-term dual antiplatelet therapy for minor stroke and transient ischemic attack is being adopted, but with the recognition that longer-term combined therapy is not worth the increased risk of bleeding. Alternative antiplatelet choices, such as cilostazol and possibly ticagrelor, may be of benefit for refractory patients and this could affect the decision-making process. This review represents an effort to incorporate the information from more recent stroke prevention and treatment studies with information gleaned from prior studies.

Prevalence of ischemic stroke and atrial fibrillation in young patients with migraine national inpatient sample analysis.

OBJECTIVE: To estimate the prevalence of ischemic stroke (IS) and atrial fibrillation (AF) in young patients with migraine and to identify the independent predictors of IS in a large cohort of hospitalized patients. METHODS: A cohort of patients with migraine with aura (MA) and migraine without aura (MO) was identified from the National Inpatient Sample database for the years 2012 to 2015. Ischemic stroke was identified by the International Classification of Diseases-9-CM codes. Binary logistic regression and Chi-square tests were utilized. RESULTS: A total number of 834,875 young patients (18-44 years) were included in this study with a mean age of 33 years. The prevalence of IS was 1.3% and was significantly higher in patients with MA (3.7% versus 1.2%, P <0.001). The prevalence of AF was 0.9% and it was significantly higher in patients with MA (1.2% versus 0.8%, P <0.001). Migraine with aura was an independent predictor of IS (OR 3.23, 95% CI 3.05-3.42, P <0.001) and AF (OR 1.63, 95% CI 1.42-1.88, P <0.001). Other predictors of IS were hypertension (OR 2.2, 95% CI 2.12-2.3, P <0.001), diabetes mellitus (DM) (OR 1.37, 95% CI 1.31-1.42, P <0.001), peripheral vascular disease (PVD) (OR 12.08, 95% CI 11.23-12.98, P <0.001) and smoking (OR 1.37, 95% CI 1.31-1.42, P <0.001). CONCLUSION: In this relatively large study, the overall prevalence of IS in young migraine patients was low at 1.3%. The prevalence of IS and AF was significantly higher in patients with MA. Presence of PVD confers a high risk of IS in young patients with migraine. Migraine aura was observed to be an independent predictor of IS and AF in patients with history of migraine. Optimal control of vascular risk factors in migraine patients appears to be indicated despite the overall low risk.

Cognitive impairment assessment and interventions to optimize surgical patient outcomes.

For elderly patients undergoing elective surgical procedures, preoperative evaluation of cognition is often overlooked. Patients may experience postoperative delirium (POD) and postoperative cognitive decline (POCD), especially those with certain risk factors, including advanced age. Preoperative cognitive impairment is a leading risk factor for both POD and POCD, and studies have noted that identifying these deficiencies is critical during the preoperative period so that appropriate preventive strategies can be implemented. Comprehensive geriatric assessment is a useful approach which evaluates a patient's medical, psycho-social, and functional domains objectively. Various screening tools are available for preoperatively identifying patients with cognitive impairment. The Enhanced Recovery After Surgery (ERAS) protocols have been discussed in the context of prehabilitation as an effort to optimize a patient's physical status prior to surgery and decrease the risk of POD and POCD. Evidence-based protocols are warranted to standardize care in efforts to effectively meet the needs of these patients.

Factors Associated with Inpatient Mortality after Intracerebral Hemorrhage: Updated Information from the United States Nationwide Inpatient Sample.

BACKGROUND: To use a nationwide database of hospital admissions to assess for trends in inpatient mortality from acute spontaneous intracerebral hemorrhage as well as associated potentially contributing factors. METHODS: Adults with intracerebral hemorrhage in the US National Inpatient Sample database from 2012 to 2015 were included in this study. We assessed for mortality rate as well as potential impact of various comorbidities and demographic factors such as ethnicity and median house hold income on inpatient mortality rate. RESULTS: A total of 47,700 patients were identified with a mean age of 68 years. The overall mortality rate was 24%. Hypertension was the commonest comorbidity (84%) followed by diabetes mellitus (28%). Positive associated factors for mortality rate were coagulopathy (OR 1.28, 95% CI 1.19-1.38, P < .001), female gender (OR 1.12, 95% CI 1.08-1.17, P < .001), and congestive heart failure (OR 1.16, 95% CI 1.08-1.24, P < .001). Age greater than 75 was also associated with higher mortality (P < .001). Factors associated with reduced mortality were hypertension (OR .76, 95% CI .72-0.81, P < .001), hypothyroidism (OR .87, 95% CI .81-.93, P < .001) and obesity (OR .64, 95% CI .59-.69, P < .001). CONCLUSIONS: The inpatient mortality of 24% represents a decline when compared to previous years. Attention to the associated factors with mortality, that we report, could have some potential impact on management. Of interest, we found support for obesity paradox in which obesity may have an actual salutary effect on vascular disease outcome. Our observed paradoxical effects, not only for obesity, but also hypertension and hypothyroidism, warrant further study.

The Relationship Between Obstructive Sleep Apnea and Ruptured Intracranial Aneurysms.

STUDY OBJECTIVES: The role of obstructive sleep apnea (OSA) in the overall outcome of ruptured intracranial aneurysms (RIAs) is unknown. We have investigated the role of OSA in overall outcome of RIAs. METHODS: Data from 159 consecutive patients were retrospectively reviewed. A chi-square test and regression analysis were performed to determine the significant difference. A value of P < .05 was considered significant. RESULTS: The prevalence of OSA in RIAs was fivefold higher in the nonaneurysm patient group, P = .002. The number of patients with hypertension (P < .0001), body mass index ≥ 30 (P < .0001), hyperlipidemia (P = .018), chronic heart disease (P = .002) or prior ischemic stroke (P = .001) was significantly higher in the OSA group. Similarly, the number of wide-neck aneurysms (P < .0001) and aneurysm > 7 mm (P = .004), poor Hunt and Hess grade IV-V (P = .005), vasospasms, (P = .03), and patients with poor Modified Rankin Scale scores (3-6) was significantly higher in the OSA group (P < .0001). Interestingly, for the first time in univariate (P = .01) and multivariate (P = .003) regression analysis, OSA was identified as an individual predictor of unfavorable outcome of RIAs. In addition, hypertension (P = .04), smoking (P = .049), chronic heart disease (P = .01), and Hunt and Hess grade IV-V (P = .04) were revealed as predictors of poor outcome of RIAs. CONCLUSIONS: This is a novel study to determine the association between OSA and ruptured cerebral aneurysm in terms of comorbidities, size of aneurysm, severity of symptoms, and outcomes after treatment. In addition, for the first time, OSA is identified as a positive predictor of unfavorable outcome of RIAs.

WEST NILE VIRUS MENINGO-ENCEPHALITIS: POSSIBLE SEXUAL TRANSMISSION.

PURPOSE: We report a previously healthy middle aged woman who developed West Nile virus meningo-encephalitis within two weeks of unprotected vaginal intercourse with her husband. SUBJECT: This patient's husband had serologically confirmed West Nile virus infection manifested by a flu-like illness and rash with the sexual contact one day before the onset of his symptoms. RESULT: This well documented neuroinvasive West Nile virus infection in our patient was within the incubation period of transmission and there was no reported mosquito bite exposure. CONCLUSION: The timeframe of infection raises the possibility that her illness was sexually transmitted.