Assessing the individual risk of stroke in caregivers of patients with stroke.

BACKGROUND: Genetic factors influence the risk of developing stroke. Still, it is unclear whether this risk is intrinsically high in certain people or if nongenetic factors explain it entirely. OBJECTIVE: To compare the risk of stroke in kin and nonkin caregivers. METHODS: In a cross-sectional study using the Stroke Riskometer app (AUT Ventures Limited, Auckland, AUK, New Zealand), we determined the 5- and 10-year stroke risk (SR) among caregivers of stroke inpatients. The degree of kinship was rated with a score ranging from 0 to 50 points. RESULTS: We studied 278 caregivers (69.4% of them female) with a mean age of 47.5 ± 14.2 years. Kin caregivers represented 70.1% of the sample, and 49.6% of them were offspring. The median SR at 5 years was of 2.1 (range: 0.35-17.3) versus 1.73 (range: 0.04-29.9), and of 4.0 (range: 0.45-38.6) versus 2.94 (range: 0.05-59.35) at 10 years for the nonkin and kin caregivers respectively. In linear logistic regression controlled for the age of the caregivers, adding the kinship score did not increase the overall variability of the model for the risk at 5 years (R2 = 0.271; p = 0.858) nor the risk at 10 years (R2 = 0.376; p = 0.78). CONCLUSION: Caregivers of stroke patients carry a high SR regardless of their degree of kinship.

ANTECEDENTES: Los factores genéticos probablemente influyen en el riesgo de desarrollar enfermedad vascular cerebral (EVC), pero no está claro si el riesgo es intrínsecamente alto o si es totalmente explicado por factores modificables. OBJETIVO: Comparar el riesgo de EVC (REVC) en cuidadores pertenecientes y no pertenecientes a la misma familia de pacientes con EVC. MéTODOS: En un estudio transversal que utilizó la aplicación Stroke Riskometer (AUT Ventures Limited, Auckland, AUK, Nueva Zelanda), determinamos el REVC a 5 y 10 años en cuidadores de pacientes hospitalizados por EVC. El grado de parentesco se graduó con un puntaje de 0 a 50 dependiendo de su relación familiar con el paciente. RESULTADOS: Estudiamos a 278 cuidadores (69.4% de ellos mujeres) con edad media de 47.5 ± 14.2 años. Los cuidadores familiares representaron el 70.1% de la muestra, siendo el 49.6% hijos. Las medianas de REVC a 5 años fueron de 2.1 (rango: 0.35­17.3) versus 1.73 (rango: 0.04­29.9), y de 4.0 (rango: 0.45­38.6) versus 2.94 (rango: 0.05­59.35) a 10 años para el grupo de cuidadores familiares y no familiares, respectivamente. En una regresión logística lineal contralando para la edad de los cuidadores, la adición del puntaje de parentesco no incrementó la variabilidad general del modelo para el riesgo a 5 años (R2 = 0.271; p = 0.858) ni para el riesgo a 10 años (R2 = 0.376; p = 0.78). CONCLUSIóN: Los cuidadores de pacientes con EVC tienen un REVC alto, independientemente de su grado de parentesco.

Delivering acute stroke care in a middle-income country. The Mexican model: "ResISSSTE Cerebro".

Introduction: Founded in 2019, the "ResISSSTE Cerebro" program is the first and only stroke network within the Mexican public health system. One advanced stroke center (ASC) and seven essential stroke centers (ESC) provide acute stroke (AS) care through a modified hub-and-spoke model. This study describes the workflow, metrics, and outcomes in AS obtained during the program's third year of operation. Materials and methods: Participants were adult beneficiaries of the ISSSTE health system in Mexico City with acute focal neurological deficit within 24 h of symptom onset. Initial evaluation could occur at any facility, but the stroke team at the ASC took all decisions regarding treatment and transfers of patients. Registered variables included demographics, stroke risk factors, AS treatment workflow time points, and clinical outcome measures. Results: We analyzed data from 236 patients, 104 (44.3%) men with a median age of 71 years. Sixty percent of the patients were initially evaluated at the ESC, and 122 (85.9%) were transferred to the ASC. The median transfer time was 123 min. The most common risk factor was hypertension (73.6%). Stroke subtypes were ischemic (86.0%) and hemorrhagic (14.0%). Median times for onset-to-door, door-to-imaging, door-to-needle, and door-to-groin were: 135.5, 37.0, 76.0, and 151.5 min, respectively. The rate of intravenous thrombolysis was 35%. Large vessel occlusion was present in 63 patients, from whom 44% received endovascular therapy; 71.4% achieved early clinical improvement (median NIHSS reduction of 11 points). Treatment-associated morbimortality was 3.4%. Conclusion: With the implementation of a modified hub-and-spoke model, this study shows that delivery of AS care in low- and middle-income countries is feasible and achieves good clinical outcomes.

Fatal arrhythmia following ingestion of hawthorn root (Crataegus pubescens) extract: a case report.

The use of extracts from the hawthorn plant as cardiovascular agents dates back to the 1st century; recently, they have also been made available online as weight loss aids. Herein, we present a case of intentional intoxication with hawthorn root extract (HRE) in an adult patient that resulted in death. A 20-year-old female patient, who was clinically diagnosed with depression, developed hypotension, bradycardia, and depressed consciousness after ingestion of this extract. An electrocardiogram recorded a sinus arrest with a slow nodal rhythm, which rapidly deteriorated, leading to cardiac arrest. This case report illustrates the potentially fatal consequences of HRE for which the constituents have not yet been characterized. All physicians, especially those in the emergency department, should be aware of the dangerous, even potentially fatal interactions of HRE with prescription medications.

Content and Quality of Information about Stroke in Wikipedia across Multiple Languages.

BACKGROUND: Given the high contribution of stroke to the global burden of disease, there is a need for good-quality information on Web platforms such as Wikipedia. AIMS: This study aimed to describe the quality of the Wikipedia articles on stroke written in different languages. METHODS: We studied the world's 30 most spoken languages. With the DISCERN score, we evaluated the quality of the information within the Wikipedia articles. Three investigators assessed each of the texts translated to English. We also registered the word count, the number of references, and if the text referred to the emergency status of stroke, cues to suspect a stroke, and allusions to endovascular treatment. RESULTS: There is a Wikipedia article for stroke in 23 out of the 30 languages. The mean DISCERN score was 35 29.9 ± 9.2. Overall quality ranged from 3/5 in 26.1% to 1/5 in 17.4%. Word count had a mean of 36 3,145.8 ± 3,048.9 words, and the texts included a mean of 43.1 ± 57.3 references; 69.6% of the articles referred to stroke as a medical emergency, 52.2% included awareness symptoms, and 34.8% included endovascular management among the stroke treatments. Three pages included steroids as part of the stroke treatment. The DISCERN score was not correlated with the number of speakers, but it was positively correlated with the number of references (r = 0.90, p < 0.001) and the number of words (r = 0.78, p < 0.001) in the articles. CONCLUSION: The analyzed Wikipedia articles do not contain relevant and up-to-date information to the general population. Further, the content varies widely across the different languages and is missing for some of them. The missing versions disproportionally affect millions of potential information seekers in undeveloped countries.

Matrix metalloproteinase-2 and matrix metalloproteinase-9 serum levels in patients with vertebrobasilar dolichoectasia with and without stroke: case-control study.

PURPOSE: To describe the differences in the serum levels of MMP-2 and MMP-9 of patients with vertebrobasilar dolichoectasia (VBD) with and without acute stroke. METHODS: Case-control study. From an outpatient clinic, we recruited 14 controls and 19 patients with VBD. We also recruited 33 patients with stroke from two emergency departments, 14 without VBD (S/-VBD) and 19 with VBD (S/ + VBD). All the patients underwent serum MMP-2 and MMP-9 measurements and a non-contrast CT scan. Two investigators assessed the intracranial vertebral arteries (VA) and the basilar artery (BA) at the mid-pons. Diagnosis of VBD was made if the BA diameter was ≥ 4.5 mm. RESULTS: The mean age of the 66 patients studied was 57.6 + 16.0 years, 41% female. In the 33 patients with stroke, the median NIHSS was 8 (range 15); there were no differences in the NIHSS scores between both groups with stroke. Median MMP-2 levels were lower in the S/-VBD when compared to controls. Median MMP-9 serum levels were higher in both groups with VBD when compared to controls and the S/-VDB group. Both groups with stroke exhibited higher MMP-9 serum levels than controls but were not statistically different from those found in patients with VBD. Serum levels of MMP-9 were significantly correlated with the diameters of the BA (r = 0.344, p = 0.01) and the left VA (r = 0.305, p = 0.05). CONCLUSION: This study found that high serum levels of MMP-9 are associated with VBD independently of stroke and correlated with the degree of VBD.

COVID-19 Lockdown Effects on Acute Stroke Care in Latin America.

OBJECTIVES: COVID-19 pandemic has forced important changes in health care worldwide. Stroke care networks have been affected, especially during peak periods. We assessed the impact of the pandemic and lockdowns in stroke admissions and care in Latin America. MATERIALS AND METHODS: A multinational study (7 countries, 18 centers) of patients admitted during the pandemic outbreak (March-June 2020). Comparisons were made with the same period in 2019. Numbers of cases, stroke etiology and severity, acute care and hospitalization outcomes were assessed. RESULTS: Most countries reported mild decreases in stroke admissions compared to the same period of 2019 (1187 vs. 1166, p = 0.03). Among stroke subtypes, there was a reduction in ischemic strokes (IS) admissions (78.3% vs. 73.9%, p = 0.01) compared with 2019, especially in IS with NIHSS 0-5 (50.1% vs. 44.9%, p = 0.03). A substantial increase in the proportion of stroke admissions beyond 48 h from symptoms onset was observed (13.8% vs. 20.5%, p < 0.001). Nevertheless, no differences in total reperfusion treatment rates were observed, with similar door-to-needle, door-to-CT, and door-to-groin times in both periods. Other stroke outcomes, as all-type mortality during hospitalization (4.9% vs. 9.7%, p < 0.001), length of stay (IQR 1-5 days vs. 0-9 days, p < 0.001), and likelihood to be discharged home (91.6% vs. 83.0%, p < 0.001), were compromised during COVID-19 lockdown period. CONCLUSIONS: In this Latin America survey, there was a mild decrease in admissions of IS during the COVID-19 lockdown period, with a significant delay in time to consultations and worse hospitalization outcomes.

Dose Escalation and Safety of Capsaicin for Cerebral Perfusion Augmentation: A Pilot Study.

Background and Purpose: Sphenopalatine ganglion (SPG) electrical stimulation has been studied in the setting of acute ischemic stroke to enhance collateral flow. Capsaicin poses an alternative to chemically stimulate the sphenopalatine ganglion. Therefore, the objective of this study was to determine the safety and effect of increasing doses of capsaicin upon serial transcranial Doppler markers of cerebral blood flow. Methods: We performed serial transcranial Doppler testing in 30 healthy volunteers divided into 5 equal groups. Capsaicin doses ranged from 33 to 165 µMol. We recorded peak systolic and end-diastolic velocities in the middle cerebral artery, arterial pressure, and perceived pungency in 5-minute intervals up to 20 minutes. We then calculated the mean velocity, the pulsatility index, and the cerebral blood flow index. Results: The participants' median age was 21 years (range, 5 years); all reported consumption of capsaicin in their diets. After and during the study, none reported side effects. Perceived pungency peaked at 5 minutes, and by the 20-minute mark, none perceived any pungency. All the tested doses produced the same pattern, consisting of augmentation of the middle cerebral artery mean velocity with the pulsatility index's diminution. The effects peaked between the 5- and the 10-minute measurements and then returned to basal levels except for the 66-µMol doses, which produced a sustained effect. We found no correlation between perceived pungency and dose, but the middle cerebral artery mean velocity was strongly correlated with the dose administered. Conclusions: This study provides evidence supporting the safety and tolerability of oral capsaicin in a population of healthy volunteers. Capsaicin appears to produce effects similar to those of sphenopalatine ganglion electrical stimulation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04545892.

Identification of Barriers to Access Endovascular Treatment for Acute Ischemic Stroke in the Health Care System of Mexico: Results From a National Survey Among Endovascular Neurologists.

Background: Providing endovascular treatment (EVT) access for acute ischemic stroke (AIS) is a challenge in Latin America. Even though the Mexican Endovascular Reperfusion Registry (MERR) and the RESILIENT trial have demonstrated the feasibility of EVT of AIS in Latin America, the MERR has uncovered potential challenges to delivering EVT to AIS patients. Aim: To identify the perceived barriers to access EVT for AIS in Mexico. Methods: We surveyed endovascular neurologists in Mexico. The survey addressed the situation of thrombectomy in the country and the infrastructure and resources available in the participants' institutions. The questionnaire inquired about costs, barriers, and challenges to accessing EVT for AIS, emphasizing the prices and availability of medical devices needed for EVT. Results: We analyzed data from 21 hospitals. The most extreme identified barriers to access EVT were the lack of health coverage for EVT in the National Health System, the cost of the medical supplies for EVT, and inadequate knowledge of stroke symptoms in the general population. The median cost for EVT was USD 20,000 (IQR 7,500-20,000). From this amount, 60% (IQR 50-70%) corresponded to the costs involved with medical devices. EVT carried additional out-of-pocket costs in 90% of the hospitals, and in 57%, the costs exceed USD $10,000. Conclusion: Efforts at all government levels and society are required to tackle these barriers. An increase in and efficient use of public funding for EVT coverage and the deployment of continuous and targeted stroke education campaigns could reduce inequities in EVT access in Mexico.

A Clinical Prognostic Scoring System for Neurocysticercosis.

Objectives In patients with neurocysticercosis (NCC), an accurate risk prediction would allow a better therapeutic approach; however, there are currently no tools that can enhance the accuracy of risk prediction. We designed a prognostic scoring system to be used by neurologists and other physicians managing patients with NCC. Materials and Methods Using data from clinical records of patients from a third-level national reference center for neurological diseases, we assessed demographic, clinical, and tomographic variables among 293 patients diagnosed with NCC. Multivariable logistic regression analyses were used to develop a clinical prognostic scoring instrument. Patients with NCC were assessed for neurological impairment at 3 months after diagnosis. Statistical Analysis Score accuracy was assessed by receiver operating characteristic (ROC) curve analysis. The primary outcome was the presence of neurological impairment, resulting in disability according to self-report or caregiver reports; this outcome was assessed during follow-up visits at 3 ± 1 months after discharge. Results The most common symptoms at presentation were headache (67%) and seizure (63%). A six-item (total score from -4 to + 2) prognostic instrument was constructed on the basis of the presence of seizures/headache at presentation, a leukocyte count above 12x 109/dL, the presence of six to ten parasites, subarachnoid localization, and the use of anthelmintic drugs. Among 113 patients with negative scores, 79.6% developed neurological deficits. Among patients with scores of 1 to 2, 64.6% recovered completely, with an overall accuracy of prediction of 74.7% and area under the ROC curve = 0.722 (95% CI, 0.664-0.780, p < 0.0001). Conclusions The clinical prognostic scoring system for NCC described in this study is a new instrument for use in daily clinical practice. It is simple to administer, and it has a prognostic accuracy of 75%. Its use has the potential to improve the quality of care by guiding appropriate decision-making and early management of patients with NCC.

Mood variations and personality traits in patients with epilepsy over the course of their menstrual cycle.

INTRODUCTION: The incidence of mood disorders and psychopathology is more frequent in patients with epilepsy (PWE) than in the general population. Also, it has been reported that PWE suffer more seizures during certain phases of their menstrual cycle (MC). Still, limited information exists regarding the relationship between the physical and emotional changes during the MC in PWE. Therefore, in this study, we aimed to evaluate the mood and personality traits of PWE during their MC and to compare them with controls. METHODS: A cohort of 22 PWE and nine controls was gathered. All the participants underwent psychiatric, electroencephalographic, and gynecological evaluations. RESULTS: Overall, PWE scored higher in depression compared with controls (p < 0.05), PWE also obtained higher scores for the personality traits of neuroticism and self-isolation (p < 0.05). During the evaluation of the symptoms of premenstrual syndrome (PMS), PWE were more symptomatic during the early follicular (EF) phase in comparison with the rest of the phases of their MC, whereas the control group showed the known premenstrual pattern of symptoms during the late luteal (LL) phase. The frequency of seizures (40.6%) and electroencephalographic abnormalities (34.8%) was also higher during the EF phase of the MC when compared with the other phases of the MC (p < 0.05). CONCLUSIONS: The results of this study suggest that unlike the PMS present in women without epilepsy, PWE appear to show a "menstrual syndrome" that consists of similar mood changes and physical symptoms. This arrangement of symptoms seems to have an impact on the increase in seizure activity.

Sex Differences Among Participants in the Latin American Stroke Registry.

Background Reports on sex differences in stroke outcome and risk factors are scarce in Latin America. Our objective was to analyze clinical and prognostic differences according to sex among participants in the LASE (Latin American Stroke Registry). Methods and Results Nineteen centers across Central and South America compiled data on demographics, vascular risk factors, clinical stroke description, ancillary tests, and functional outcomes at short-term follow-up of patients included from January 2012 to January 2017. For the present study, all these variables were analyzed according to sex at hospital discharge. We included 4788 patients with a median in-hospital stay of 8 days (interquartile range, 5-8); 2677 were male (median age, 66 years) and 2111 female (median age, 60 years). Ischemic stroke occurred in 4293: 3686 as cerebral infarction (77%) and 607 as transient ischemic attack cases (12.7%); 495 patients (10.3%) corresponded to intracerebral hemorrhage. Poor functional outcome (modified Rankin scale, 3-6) was present in 1662 (34.7%) patients and 38.2% of women (P<0.001). Mortality was present in 6.8% of the registry, with 7.8% in women compared with 6.0% in men (P=0.01). Death and poor functional outcome for all-type stroke showed a higher risk in female patients (hazard ratio, 1.3, P=0.03; and hazard ratio, 1.1, P=0.001, respectively). Conclusions A worse functional outcome and higher mortality rates occurred in women compared with men in the LASE, confirming sex differences issues at short-term follow-up.

Endovascular Treatment of Ischemic Stroke in a Developing Country.

BACKGROUND: There is inequality in access to recent advancements in endovascular treatment of acute ischemic stroke (AIS), and Mexico is unusually sensitive to such inequality. AIMS: To report the initial experience of the Mexican Endovascular Reperfusion Registry (MERR). METHODS: The MERR is an academic, independent, prospective, multicenter, observational registry of patients treated with endovascular reperfusion techniques in Mexican hospitals. The registry includes information on demographic and clinical characteristics, diagnostic procedures, treatments, selected time metrics, and outcomes. RESULTS: In all, 49 (57.1% female) patients from 8 centers were included and had the following characteristics: median National Institute of Health Stroke Scale score, 16; median Alberta Stroke Program Early CT Score score, 9; received intravenous tissue-type plasminogen activator, 49%; and treated with mechanical devices, 39 (79.6%), including 20 treated with stent retriever alone, 2 with retriever and intra-arterial thrombolysis (IAt), 10 with catheter aspiration (4 in combination with IAt), 6 with a combination of catheter aspiration and stent retriever, and 1 with IAt followed by balloon angioplasty. Recanalization (TICI 2b or better) was achieved in 69.4% of the patients. The median clot to recanalization time was 30 minutes. A modified Rankin scale ≤2 was achieved in 44.9% of the patients, and 68.2% of these were treated with stent retriever (P = .011). Procedure-related morbidity was 12.2%, 7 patients presented intracerebral hemorrhage (71.4% asymptomatic), and all-cause mortality was 6.1%. CONCLUSIONS: Endovascular treatment of AIS in Mexico is feasible and has an efficacy comparable to that of other countries. Still, many challenges remain, especially pertaining to high costs and difficulties in equality in access to treatment.

Fluoxetine for motor recovery after acute intracerebral hemorrhage, the FMRICH trial.

OBJECTIVES: Acute intracerebral hemorrhage (ICH) is a very common cause of disability. Previous evidence suggests that fluoxetine and other selective serotonin reuptake inhibitors improve, the recovery of motor function in patients with cerebral infarct. The purpose of this study was to investigate whether fluoxetine also improves motor recovery in patients with ICH. PATIENTS AND METHODS: This is a double blind, placebo controlled, multicenter randomized trial, patients recruited from three centers were assigned to receive 20 mg/day of fluoxetine or matching placebo for three months from within ten days after onset of symptoms. Primary outcome was change in Fugl-Meyer Motor Scale from baseline to day 90. RESULTS: Thirty patients (50 % women) were recruited to the fluoxetine (n = 14) or placebo (n = 16) groups. Median age was 55 years, the cause of the ICH was hypertension in 93.3 %, median volume of the hematomas was 22mm3. Basal ganglia hematoma was present in 67 % and, lobar location in 20 % of the patients. Improvement in FMMS at day 90 was significatively higher in the treatment group (median score 23) than in the placebo group, (median score 48), p = 0.001. No serious adverse events occurred. CONCLUSION: In addition to standard treatment, early prescription of fluoxetine was safe and helped to increase motor recovery 90 days after ICH. This finding adds to the evidence regarding its beneficial effect upon stroke related disability. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01737541.

Mexican-National Institute of Neurology and Neurosurgery-Stroke Registry: Results of a 25-Year Hospital-Based Study.

BACKGROUND AND PURPOSE: Stroke has been scarcely studied in Latin America (LA). The Mexican Institute of Neurology Stroke Registry was established in 1990 as a prospective computer-based database to register data obtained from patients admitted with stroke. Using this data, we attempted to define the profile of risk factors and outcomes. METHODS: The demographic data, stroke description, ancillary tests, vascular risk factors, and modified Rankin scale (mRs) were registered. Ischemic stroke subtyping was based on the Trial of Org 10,172 of the Acute Stroke Treatment classification. We followed-up patients using multiple overlapping methods. Primary outcomes included mRs, recurrence, and death at 30 days and at the end of follow-up. RESULTS: We included 4,481 patients with a median follow-up of 27 months, (17,281 person-years follow-up). The mean age was 52.8 ± 18 years. There were 2,229 males (50%) included in the study. CI was present in 64.9%, intracerebral hemorrhage (ICH) in 25.6%, and cerebral venous thrombosis (CVT) in 6.3%. Hypertension was the major risk factor (46.5%). The most common cause of CI was atherosclerosis (27%). ICH was mainly hypertensive (58%), and 60% of CVT were puerperal. Overall, the mortality rate was 24.5%. The recurrence rate was 16.9%. Poor outcome (mRs ≥ 3) was found in 56.2% of patients. The best outcomes were observed in CVT patients (74.5% mRs ≤ 2), whereas 72.1% ICH patients had mRs ≥3. CONCLUSION: This is one of the largest hospital-based registries in LA and shows significant differences with other previously published registries, including a younger age, relatively less hypertension, and larger proportion of CVT. Poor functional outcome was common. This study adds to the understanding of geographic differences in stroke characteristics and outcomes.

Fluoxetine for motor recovery after acute intracerebral hemorrhage (FMRICH): study protocol for a randomized, double-blind, placebo-controlled, multicenter trial.

BACKGROUND: Spontaneous, nontraumatic intracerebral hemorrhage (ICH) is a subtype of stroke that causes a great amount of disability and economic and social burden. This is particularly true in developing countries where it accounts for between 20% and 50% of all strokes. Pharmacological and surgical interventions have been attempted to reduce the mortality and disability caused by ICH, with unsuccessful results. Recently, the use of fluoxetine in addition to physical rehabilitation has been proven useful to improve motor recovery following cerebral infarct. The purpose of this study is to test whether a 3-month treatment with fluoxetine enhances motor recovery in nondepressed patients with acute intracerebral hemorrhage. METHODS/DESIGN: Our study is a randomized, double-blind, placebo-controlled, multicenter clinical trial. We will recruit 86 patients with intracerebral hemorrhage of both sexes, aged >18 years, from four Mexican hospitals. The patients will receive either 20 mg of fluoxetine or a placebo once daily for 90 days. The primary outcome is the mean change in the Fugl-Meyer Motor Scale score between inclusion (day 0) and day 90. The secondary outcomes will be changes in the Barthel Index, the Modified Rankin scale and the National Institutes of Health stroke scale. The outcomes will be measured at day 42 ± 7 days and at day 90, for a total of four visits with each subject (at screening and at 0, 42 and 90 days). DISCUSSION: Current guidelines recommend early supported hospital discharge and home-based rehabilitation programs as the only cost-effective intervention to aid the recovery of patients with intracerebral hemorrhage. Nevertheless, such interventions are dependent on available resources and funding, which make them very difficult to implement in developing countries. We believe that the identification of a helpful pharmacological intervention to aid the motor recovery of these patients will constitute a breakthrough that will have a major impact in reducing the burden of disease caused by this subtype of stroke worldwide, especially in the developing world. TRIAL REGISTRATION: Current Controlled Trials NCT01737541.