Intracranial Hemorrhage in Hospitalized SARS-CoV-2 Patients: A Case Series.

The SARS-CoV-2 virus causing Coronavirus Disease 2019 (COVID-19) is a global pandemic with almost 30 million confirmed worldwide cases. Prothrombotic complications arising from those affected with severe symptoms have been reported in various medical journals. Currently, clinical trials are underway to address the questions regarding anticoagulation dosing strategies to prevent thrombosis for these critically ill patients. However, given the increasing use of therapeutic anticoagulation in patients admitted with COVID-19 to curtail this prothrombotic state, our institution has witnessed six cases of devastating intracranial hemorrhage as well as thrombosis leading to five fatalities and we examine their hospital course and anticoagulation used.

Safety and Outcomes of Intravenous Thrombolytic Therapy in Ischemic Stroke Patients with COVID-19: CASCADE Initiative.

BACKGROUND: There is little information regarding the safety of intravenous tissue plasminogen activator (IV-tPA) in patients with stroke and COVID-19. METHODS: This multicenter study included consecutive stroke patients with and without COVID-19 treated with IV-tPA between February 18, 2019, to December 31, 2020, at 9 centers participating in the CASCADE initiative. Clinical outcomes included modified Rankin Scale (mRS) at hospital discharge, in-hospital mortality, the rate of hemorrhagic transformation. Using Bayesian multiple regression and after adjusting for variables with significant value in univariable analysis, we reported the posterior adjusted odds ratio (OR, with 95% Credible Intervals [CrI]) of the main outcomes. RESULTS: A total of 545 stroke patients, including 101 patients with COVID-19 were evaluated. Patients with COVID-19 had a more severe stroke at admission. In the study cohort, 85 (15.9%) patients had a hemorrhagic transformation, and 72 (13.1%) died in the hospital. After adjustment for confounding variables, discharge mRS score ≥2 (OR: 0.73, 95% CrI: 0.16, 3.05), in-hospital mortality (OR: 2.06, 95% CrI: 0.76, 5.53), and hemorrhagic transformation (OR: 1.514, 95% CrI: 0.66, 3.31) were similar in COVID-19 and non COVID-19 patients. High-sensitivity C reactive protein level was a predictor of hemorrhagic transformation in all cases (OR:1.01, 95%CI: 1.0026, 1.018), including those with COVID-19 (OR:1.024, 95%CI:1.002, 1.054). CONCLUSION: IV-tPA treatment in patients with acute ischemic stroke and COVID-19 was not associated with an increased risk of disability, mortality, and hemorrhagic transformation compared to those without COVID-19. IV-tPA should continue to be considered as the standard of care in patients with hyper acute stroke and COVID-19.

Stroke Care Trends During COVID-19 Pandemic in Zanjan Province, Iran. From the CASCADE Initiative: Statistical Analysis Plan and Preliminary Results.

BACKGROUND: The emergence of the COVID-19 pandemic has significantly impacted global healthcare systems and this may affect stroke care and outcomes. This study examines the changes in stroke epidemiology and care during the COVID-19 pandemic in Zanjan Province, Iran. METHODS: This study is part of the CASCADE international initiative. From February 18, 2019, to July 18, 2020, we followed ischemic and hemorrhagic stroke hospitalization rates and outcomes in Valiasr Hospital, Zanjan, Iran. We used a Bayesian hierarchical model and an interrupted time series analysis (ITS) to identify changes in stroke hospitalization rate, baseline stroke severity [measured by the National Institutes of Health Stroke Scale (NIHSS)], disability [measured by the modified Rankin Scale (mRS)], presentation time (last seen normal to hospital presentation), thrombolytic therapy rate, median door-to-needle time, length of hospital stay, and in-hospital mortality. We compared in-hospital mortality between study periods using Cox-regression model. RESULTS: During the study period, 1,026 stroke patients were hospitalized. Stroke hospitalization rates per 100,000 population decreased from 68.09 before the pandemic to 44.50 during the pandemic, with a significant decline in both Bayesian [Beta: -1.034; Standard Error (SE): 0.22, 95% CrI: -1.48, -0.59] and ITS analysis (estimate: -1.03, SE = 0.24, p < 0.0001). Furthermore, we observed lower admission rates for patients with mild (NIHSS < 5) ischemic stroke (p < 0.0001). Although, the presentation time and door-to-needle time did not change during the pandemic, a lower proportion of patients received thrombolysis (-10.1%; p = 0.004). We did not see significant changes in admission rate to the stroke unit and in-hospital mortality rate; however, disability at discharge increased (p < 0.0001). CONCLUSION: In Zanjan, Iran, the COVID-19 pandemic has significantly impacted stroke outcomes and altered the delivery of stroke care. Observed lower admission rates for milder stroke may possibly be due to fear of exposure related to COVID-19. The decrease in patients treated with thrombolysis and the increased disability at discharge may indicate changes in the delivery of stroke care and increased pressure on existing stroke acute and subacute services. The results of this research will contribute to a similar analysis of the larger CASCADE dataset in order to confirm findings at a global scale and improve measures to ensure the best quality of care for stroke patients during the COVID-19 pandemic.

Neurologic Complications in the Intensive Care Unit.

Complications involving the central and peripheral nervous system are frequently encountered in critically ill patients. All components of the neuraxis can be involved including the brain, spinal cord, peripheral nerves, neuromuscular junction, and muscles. Neurologic complications adversely impact outcome and length of stay. These complications can be related to underlying critical illness, pre-existing comorbid conditions, and commonly used and life-saving procedures and medications. Familiarity with the myriad neurologic complications that occur in the intensive care unit can facilitate their timely recognition and treatment. Additionally, awareness of treatment-related neurologic complications may inform decision-making, mitigate risk, and improve outcomes.

Cervicocerebral artery dissection.

PURPOSE OF REVIEW: The purpose of this article is to review the epidemiology, pathophysiology, risk factors, clinical manifestations, diagnostic methods and current treatment options for cervicocerebral artery dissection (CCD). RECENT FINDINGS: CCD incidence has increased over time largely because of improvements in and increasing availability of noninvasive imaging. CCD can be detected on computed tomography angiography, MRI, magnetic resonance angiography, carotid duplex ultrasonography and conventional catheter-based digital subtraction angiography. Additionally, ischemic stroke treatment with intravenous tissue plasminogen-activator for patients with suspected CCD appears to be well tolerated and effective. Moreover, a randomized clinical trial has shown antiplatelet agents to be as effective as anticoagulants at preventing recurrent ischemia. Surgical and endovascular techniques can be considered particularly for patients presenting with intracranial arterial dissection causing subarachnoid hemorrhage, developing recurrent ischemia due to hemodynamic impairment and whose dissecting aneurysms cause brainstem compression. SUMMARY: CCD is an important and one of the most common causes of ischemic stroke in young patients without traditional vascular risk factors. Cases can occur shortly after trauma. However, spontaneous CCD is common and is associated with many genetic, acquired and anatomical risk factors. CCD should be detected early to avoid complications and prevent long-term disability.

Neurology of rheumatologic disorders.

Rheumatologic diseases encompass autoimmune and inflammatory disorders of the joints and soft tissues that often involve multiple organ systems, including the central and peripheral nervous systems. Common features include constitutional symptoms, arthralgia and arthritis, myalgia, and sicca symptoms. Neurological manifestations may present in patients with preexisting rheumatologic diagnoses, occur concurrently with systemic signs and symptoms, or precede systemic manifestations by months to years. Rheumatic disorders presenting as neurological syndromes may pose diagnostic challenges. Advances in immunosuppressive treatment of rheumatologic disease have expanded the treatment armamentarium. However, serious neurotoxic effects have been reported with both old and newer agents. Familiarity with neurological manifestations of rheumatologic diseases, diagnosis, and potential nervous system consequences of treatment is important for rapid diagnosis and appropriate intervention. This article briefly reviews the diverse neurological manifestations and key clinical features of rheumatic disorders and the potential neurological complications of agents commonly used for treatment.

Reversible cerebral vasoconstriction syndrome with multivessel cervical artery dissections and a double aortic arch.

Reversible cerebral vasoconstriction syndrome (RCVS) has been associated with exposure to vasoactive substances and few reports with cervical arterial dissections (CADs). We evaluated a 32-year-old woman with history of depression, migraines without aura, and cannabis use who presented with a thunderclap headache unresponsive to triptans. She was found to have bilateral occipital infarcts, bilateral extracranial vertebral artery dissections, bilateral internal carotid artery dissecting aneurysms, and extensive distal multifocal segmental narrowing of the anterior and posterior intracranial circulation with a "sausage on a string-like appearance" suggestive of RCVS. Subsequently, she was found to have a distal thrombus of the basilar artery, was anticoagulated, and discharged home with no residual deficits. We highlight the potential association of CADs and RCVS. The association of RCVS and a double aortic arch has not been previously reported.

Telemedicine in stroke care and rehabilitation.

Telemedicine allows prompt assessment of acute stroke patients. This new technology has increased the administration of intravenous recombinant tissue plasminogen activator (rtPA) to eligible patients. In addition, telemedicine is being utilized in the rehabilitation of patients with cerebrovascular disease. This article will review the use of telemedicine in patients with acute ischemic stroke and its implementation in telerehabilitation to patients with residual neurologic deficits.

Prevention of venous thromboembolism in patients with hemorrhagic stroke.

Deep venous thrombosis (DVT) and pulmonary embolism (PE) are part of the spectrum of venous thromboembolism (VTE). It is one of the most frequent medical complications in stroke patients. The risk of VTE is even higher after hemorrhagic stroke. This article reviews various screening methods, diagnostic techniques, and pharmacologic as well as nonpharmacologic means of preventing VTE after hemorrhagic stroke.

Neurologic complications of cardiac arrest.

Cardiac arrest is a catastrophic event with high morbidity and mortality. Despite advances over time in cardiac arrest management and postresuscitation care, the neurologic consequences of cardiac arrest are frequently devastating to patients and their families. Targeted temperature management is an intervention aimed at limiting postanoxic injury and improving neurologic outcomes following cardiac arrest. Recovery of neurologic function governs long-term outcome after cardiac arrest and prognosticating on the potential for recovery is a heavy burden for physicians. An early and accurate estimate of the potential for recovery can establish realistic expectations and avoid futile care in those destined for a poor outcome. This chapter reviews the epidemiology, pathophysiology, therapeutic interventions, prognostication, and neurologic sequelae of cardiac arrest.

Prediction of ventriculoperitoneal shunt dependency in patients with aneurysmal subarachnoid hemorrhage.

OBJECT: Patients with subarachnoid hemorrhage treated using external ventricular drainage due to obstructive hydrocephalus commonly remain shunt-dependent. Based on identified risk factors for external ventricular drain (EVD) challenge failure, the authors sought to determine the likelihood that a patient will require a permanent shunt. METHODS: The authors reviewed 89 consecutive cases of aneurysmal subarachnoid hemorrhage with obstructive hydrocephalus for parameters associated with EVD challenge failure and permanent shunt requirement. Significant parameters were combined in a discriminant function analysis to create a failure risk index (FRI). Linear regression analysis was performed correlating the FRI with the actual rate of shunt dependency. RESULTS: Patients requiring a permanent shunt had: a larger third ventricular diameter (7.0 vs 5.4 mm; p = 0.02) and a higher Hunt and Hess grade (3 vs 2; p = 0.02) at the time of admission; and a larger third ventricular diameter (6.6 vs 5.2 mm; p = 0.04), a larger bicaudate diameter (31.9 vs 30.2 mm; p = 0.03), and higher CSF protein levels (76.5 vs 40.3 mg/dl; p < 0.0001) at the onset of EVD challenge. These patients were also more likely to be female (p = 0.01) and have a posterior circulation location of their aneurysm (p = 0.01). The FRI score was calculated based on a weighted combination of the above parameters. Linear regression analysis between FRI values and the percentage of patients who required a permanent shunt had a correlation coefficient of 91%; the risk of a permanent shunt requirement increased linearly with a rising FRI score. CONCLUSIONS: An FRI score created by discriminant function analysis can predict whether or not a permanent shunt is required, even if separate factors are not in agreement with each other or show a weak correlation when considered separately. An increased FRI score was strongly and linearly correlated with the risk of EVD challenge failure. A prospective study is necessary to validate the FRI.

Hydrocephalus in posterior fossa lesions: ventriculostomy and permanent shunt rates by diagnosis.

OBJECTIVES: The rate of ventriculostomy for acute hydrocephalus and progression to shunt-dependent chronic hydrocephalus in patients with posterior fossa lesions are not well known. METHODS: We retrospectively reviewed 104 consecutive cases with posterior fossa lesions on admission to the University of Illinois Hospital from June 2002 to December 2005. We recorded the rate of ventriculostomy and permanent ventricular shunting, which were compared among etiologic groups, using chi-squared and Fisher's exact tests. RESULTS: Overall, 35 patients had ventriculostomy for acute hydrocephalus and 16 had permanent shunting for shunt-dependent chronic hydrocephalus. Of those with primary posterior fossa intracranial hemorrhage (ICH) (42 cases), 19 (45%) required ventriculostomy, with five (26%) requiring subsequent permanent shunting; 13 patients had hematoma evacuation, with two having permanent shunting. Of those with cerebellar infarction (14 cases), four (29%) required ventriculostomy and one (25%) had a permanent shunt; two had a decompressive craniectomy. Of those with neoplasms (43 cases, 33 surgically resected), ten (23%) required ventriculostomy and nine (21%) required permanent shunting. In addition, two of the three cases with infectious processes required ventriculostomy and one required a permanent shunt. In-hospital mortality was 21% (9/42 cases) for patients with ICH, 14% (2/14 cases) for patients with infarction and 0% for all others. DISCUSSION: Acute primary posterior fossa hemorrhage has the highest rate of ventriculostomy for acute hydrocephalus and highest inpatient mortality but a surprisingly low rate of permanent shunt-dependency. When hydrocephalus was caused by a neoplasm, there was a higher rate of permanent shunt placement.

Safety of clopidogrel and aspirin for stroke prevention: implications of the CHARISMA trial.

Antiplatelet therapy is universally recommended for the prevention of recurrent events in patients with noncardioembolic ischaemic stroke or transient ischaemic attack (TIA), acute and chronic coronary artery disease, or peripheral arterial disease. However, choosing which antiplatelet agents to use in these situations remains controversial. The use of aspirin, aspirin plus extended-release dipyridamole, or clopidogrel is recommended as initial therapy in patients with noncardioembolic ischaemic stroke or TIA to reduce the risk of recurrent stroke and other cardiovascular events. Based on the results of the MATCH trial, combination therapy with aspirin plus clopidogrel is not recommended for patients with ischaemic stroke or TIA due to the increased risk of haemorrhage. The results of the CHARISMA trial support this recommendation; despite previous data demonstrating a favourable benefit-risk profile of aspirin plus clopidogrel in patients with acute coronary syndrome, this combination should not be used in patients at high risk for atherothrombosis and those with previous stroke or TIA. In these patients, the CHARISMA trial demonstrated a lack of significant clinical efficacy and an increased risk of bleeding with clopidogrel plus aspirin compared with aspirin alone. Further research is needed to assess the benefit-risk ratio of clopidogrel plus aspirin in specific subpopulations of patients at high risk for atherothrombotic events, and to determine the role of clopidogrel plus aspirin in preventing cardioembolic stroke or early recurrent stroke after symptomatic large-vessel atherostenosis. Recent and ongoing studies are seeking to better define the roles of different antiplatelet regimens in preventing recurrent stroke.

Cortical stimulation for the rehabilitation of patients with hemiparetic stroke: a multicenter feasibility study of safety and efficacy.

OBJECT: In this prospective multicenter study the authors hypothesized that investigational epidural cortical stimulation (CS) delivered concurrently with rehabilitation therapy may enhance motor recovery following stroke. METHODS: Patients who had suffered their index stroke >or= 4 months previously were randomized into 6 weeks of rehabilitation therapy with or without CS. Cortical stimulation, targeted by functional imaging, was delivered at approximately 50% of motor movement threshold. Primary outcome measures were Upper Extremity Fugl-Meyer (UEFM [a measure of neurological and motor function]) and Arm Motor Ability Test (AMAT [a measure of activities of daily living]) scores. The primary study end point was 4 weeks following rehabilitation therapy. RESULTS: A total of 24 patients, 12 per group, completed the treatment protocol. The mean interval since the patients' index stroke was 33 months (range 4-100 months). There were no deaths or cases of neurological deterioration; 1 acute postoperative seizure occurred unrelated to the device or treatment. Patients who underwent CS experienced improved hand/arm function more than control patients. The UEFM score improved 5.5 +/- 4.4 points in patients in the CS group compared with 1.9 +/- 4.4 points for controls (p = 0.03). A 3.5-point UEFM improvement is considered clinically meaningful. The AMAT scores for the CS group improved by 0.4 +/- 0.6 points, whereas the scores in the control group improved by 0.2 +/- 0.4 points (p = 0.2). A 0.21-point improvement in AMAT score is considered clinically meaningful. In the CS group, 67% of patients had clinically meaningful improvement in UEFM scores, compared with 25% of the control group (p = 0.05). Of patients in the CS group 50% had clinically meaningful improvement in UEFM as well as AMAT scores, compared with only 8% of those in the control group (p = 0.03). CONCLUSIONS: These results suggest that subthreshold epidural CS is safe and effective during rehabilitation for recovery of arm and hand function following hemiparetic stroke. Further research in a larger cohort is needed to validate the therapeutic effect.

A comparison of the blood pressure changes of lumiracoxib with those of ibuprofen and naproxen.

The 52-week Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET) investigated the gastrointestinal and cardiovascular safety profile of lumiracoxib 400 mg once daily compared with 2 traditional nonsteroidal anti-inflammatory drugs (NSAIDs): ibuprofen 800 mg 3 times daily and naproxen 500 mg twice daily. Data from TARGET were analyzed to examine the effect of lumiracoxib compared with ibuprofen and naproxen on blood pressure (BP), incidence of de novo and aggravated hypertension, prespecified edema events, and congestive heart failure. Lumiracoxib resulted in smaller changes in BP as early as week 4. Least-squares mean change from baseline at week 4 for systolic BP was +0.57 mm Hg with lumiracoxib compared with +3.14 mm Hg with ibuprofen (P<.0001) and +0.43 with lumiracoxib compared with +1.80 mm Hg with naproxen (P<.0001). In conclusion, the use of lumiracoxib and traditional NSAIDs results in differing BP changes; these might be of clinical relevance.

Cortical stimulation for upper limb recovery following ischemic stroke: a small phase II pilot study of a fully implanted stimulator.

OBJECTIVE: To evaluate the feasibility of a fully implanted cortical stimulator for improving hand and arm function in patients following ischemic stroke. METHOD: Twenty-four chronic stroke patients with hemiplegia were randomized to targeted implanted cortical electrical stimulation of the motor cortex with upper limb rehabilitation therapy or rehabilitation therapy alone. RESULTS: Using repeated measures regression models, we estimated and compared treatment effects between groups over the study follow-up period. The investigational group had significantly greater mean improvements in Upper Extremity Fugl-Meyer (UEFM) scores during the 6-month follow-up period (weeks 1-24 following therapy), as compared to the control group (difference in estimated means = 3.8, p = .042). Box and Block (B & B) test improvement from baseline scores were also significantly better in the investigational group across the 6-month follow-up assessments (difference in estimated means = 3.8, p = .046). There was one report of seizure after device implant but prior to cortical stimulation and rehabilitation therapy, but no reports of neurologic decline. There were no improvements seen in the other measures assessed. CONCLUSION: Evidence suggests that cortical stimulation with rehabilitation therapy produces a lasting treatment effect in upper extremity motor control and is not associated with serious neurological complications. A larger multicenter study is underway.

Predicting functional gains in a stroke trial.

BACKGROUND AND PURPOSE: A number of therapies in development for patients with central nervous system injury aim to reduce disability by improving function of surviving brain elements rather than by salvaging tissue. The current study tested the hypothesis that, after adjusting for a number of clinical assessments, a measure of brain function at baseline would improve prediction of behavioral gains after treatment. METHODS: Twenty-four patients with chronic stroke underwent baseline clinical and functional MRI assessments, received 6 weeks of rehabilitation therapy with or without investigational motor cortex stimulation, and then had repeat assessments. Thirteen baseline clinical/radiological measures were evaluated for ability to predict subsequent trial-related gains. RESULTS: Across all patients, bivariate analyses found that greater trial-related functional gains were predicted by (1) smaller infarct volume, (2) greater baseline clinical status, and (3) lower degree of activation in stroke-affected motor cortex on baseline functional MRI. When these 3 variables were further assessed using multivariate linear regression modeling, only lower motor cortex activation and greater clinical status at baseline remained significant predictors. Note that lower baseline motor cortex activation was also associated with larger increases in motor cortex activation after treatment. CONCLUSIONS: Lower motor cortex activity at baseline predicted greater behavioral gains after therapy, even after controlling for a number of clinical assessments. The boosts in cortical activity that paralleled behavioral gains suggest that in some patients, low baseline cortical activity represents underuse of surviving cortical resources. A measure of brain function might be important for optimal clinical decision-making in the context of a restorative intervention.

Leucine-Rich Glioma Inactivated-1 and Voltage-Gated Potassium Channel Autoimmune Encephalitis Associated with Ischemic Stroke: A Case Report.

Autoimmune encephalitis is associated with a wide variety of antibodies and clinical presentations. Voltage-gated potassium channel (VGKC) antibodies are a cause of autoimmune non-paraneoplastic encephalitis characterized by memory impairment, psychiatric symptoms, and seizures. We present a case of VGKC encephalitis likely preceding an ischemic stroke. Reports of autoimmune encephalitis associated with ischemic stroke are rare. Several hypotheses linking these two disease processes are proposed.

Impact of obesity and the metabolic syndrome on risk factors in African American stroke survivors: a report from the AAASPS.

BACKGROUND: The rates of obesity and the metabolic syndrome and the impact on traditional vascular risk factors in African American stroke survivors are unknown. OBJECTIVE: To describe the relationships between body mass index (BMI) (calculated as weight in kilograms divided by the square of height in meters) and hypertension, dyslipidemia, and diabetes mellitus. DESIGN: We classified 1711 subjects as underweight (BMI, <18.5), normal (BMI, 18.5-24.9), overweight (BMI, 25.0-29.9), or obesity class 1 (BMI, 30.0-34.9), 2 (BMI, 35.0-39.9), or 3 (BMI, >40.0). We compared the proportions with hypertension, dyslipidemia, and diabetes mellitus and control of these factors by clinical history and results of physical examination and laboratory analysis across BMI groups. SETTING: Multicentered clinical trial. PATIENTS: African American subjects with previous ischemic stroke. MAIN OUTCOME MEASURES: Rates of obesity and the metabolic syndrome, odds ratios (ORs) of associated vascular risk factors at baseline, and relationship to longitudinal risk factor control. RESULTS: Overall, 76% were overweight or obese (70% of men and 81% of women). Hypertension, dyslipidemia, and diabetes mellitus were all present in 43.3% of men and 29.1% of women with obesity class 3. The ORs for having the metabolic syndrome were 2.14 (95% confidence interval [CI], 1.52-3.01) for class 1, 1.92 (95% CI, 1.26-2.91) for class 2, and 1.98 (95% CI, 1.27-3.09) for class 3 obesity. In addition, increasing BMI was negatively associated with systolic (P<.001) and diastolic (P<.001) blood pressure and glycemic control (P<.001). CONCLUSION: Our analysis of the data from the African American Antiplatelet Stroke Prevention Study supports the association of increasing risk factor profiles with increasing weight in African American stroke survivors.