The budget impact of alteplase in the treatment of acute ischemic stroke in Egypt.

Introduction: Stroke is the second leading cause of mortality worldwide. Five percent of all the disability-adjusted life years (DALYs) lost around the world are attributed to stroke. This study aimed to assess the economic burden of acute ischemic stroke (AIS) in Egypt and reveal the benefits of alteplase treatment by measuring the resource use and costs associated with this treatment compared to the standard of care and extrapolate the overall budget impact of alteplase to the local Egyptian setting over a 5-year time horizon from a societal perspective. Methods: A budget impact model was developed to estimate the impact of adding alteplase to the current treatment of AIS patients within the Egyptian healthcare setting. The efficacy data for both arms of the model were sourced from a systematic review of the literature. Resource use and cost data were sourced from a retrospective study. Proportions of patients potentially eligible for treatment and the treatment time distributions were estimated from an analysis of the results of this retrospective data collection. A univariate sensitivity analysis was conducted to assess the robustness of the model results. The input parameters varied between plausible extremes based on a review of available evidence. Results: The total annual costs with alteplase treatment [i.e., drug, symptomatic intracerebral hemorrhage (ICH) management, acute hospitalization, and post-hospitalization costs] for the targeted patients from a societal perspective were estimated to be less than the total annual costs without alteplase. This resulted in savings of approximately EGP 37.2 million ($ 1.2 million), EGP 14.2 million ($ 458.06), EGP -33.0 million ($ -1.06 million), EGP -54.0 million ($ -1.74 million), and EGP -89.8 million ($ -2.89 million) for each of the 5 years, respectively. In year 1, more than 2,787 patients (+30.1%) achieved an excellent outcome and <1,204 patients (-22.3%) had a poor outcome when treated with alteplase. The savings in acute hospitalization and post-hospitalization costs offset the increase in drug and ICH management costs in the alteplase group compared to treatment without alteplase. The total cumulative cost savings for alteplase in AIS patients were estimated at EGP -228,146,871 ($ -7,359,576) over 5 years. Conclusion: The budget impact model estimates suggest that from a societal perspective, alteplase is likely to be a cost-saving option for the treatment of AIS in Egypt due to the treatment benefits, resulting in savings in acute hospitalization and annual post-hospitalization costs.

Stroke services in MENA: What is there and what is needed.

OBJECTIVES: Stroke represents a health care challenge to most parts of the world including the Middle East and North Africa (MENA) region. The MENA represents 6% of the world population with an age-standardized stroke rate of 87.7 (78.2-97.6) per 100,000 population. This number is subject to increase given that the cause of morbidity has recently shifted from infectious diseases to non-communicable diseases. Thus, in the coming years, treatment of stroke will pose a major burden on MENA countries which mostly lie in the low to middle income economies. Accordingly, we need to study the state of MENA stroke services in order to recognize and further inform policy makers about any gaps that need to be bridged in this domain. METHODS AND RESULTS: Stroke specialists representing 16 countries filled an online survey that included: screening for risk factors, acute management, diagnostics, medications, post-discharge services, and stroke registries. Results showed that 11 countries screen for risk factors, 16 have neuroimaging studies, 15 provide intravenous thrombolysis (IVT), 13 mechanical thrombectomy (MT) while medications for secondary prevention are available in all countries. However, stroke units are not equally available and even absent in 4 countries, and despite the availability of IVT yet, the rate of administration is still low in 6 countries (<5%), and ranges from 5-20% in 7 countries. Stroke registries and training still need to be implemented in most countries. CONCLUSION: Although imaging, revascularization therapies and medications for secondary prevention are available in most MENA countries, yet the rate of revascularization is low, so is the number of stroke units insufficient in some countries. Additionally, registries and structured training are still defective. Further field studies are required for more accurate determination of the status of stroke services in the MENA region.

Stroke in women: experience in a developing country.

BACKGROUND: Several studies have addressed gender differences in stroke. Yet, results are diverse, and research is still required in different populations. So, this study investigates variation in stroke according to gender in a developing country. METHODS: This is a registry-based, retrospective observational cross-sectional study comparing men and women as regards age, risk factors, stroke severity, quality of services, and stroke outcome. RESULTS: Data analyzed comprised 4620 patients. It was found that men outnumbered women, while women had an older age, more prevalence of hypertension and atrial fibrillation, with severer strokes and worse outcomes. However, there was no gender difference in promptness nor frequency of administration of revascularization therapies. CONCLUSION: Despite the gender difference in risk factors and stroke severity, we could not detect any significant disparity in acute stroke services provided to either gender. Among age categories in women, we identified differences in acute ischemic stroke subtypes, and acute management in favor of older age.

Lateralized readiness potentials can identify hemisphere of recovery in stroke patients.

BACKGROUND: Event related cortical potentials related to motor action are referred to as movement related cortical potentials. The late component of which is the readiness potential (RP) and its polarity is more negative in the hemisphere responsible for planning of motor action. This lateralized nature of RP during unilateral hand movement is studied as lateralized readiness potential (LRP) by calculating the contralateral-minus-ipsilateral difference wave for each hand. OBJECTIVE: The aim was to identify the hemisphere contributing to motor recovery in acute and chronic stroke patients through recording LRPs. METHODS: Twenty-nine cases with cerebrovascular stroke (15 acute and 14 chronic) were included in the study. EEG was recorded in response to self-cued button presses by the paretic side to obtain the averaged LRP amplitude. The hemisphere with greater negativity was considered the side of recovery. Functional recovery was assessed by Fugl Meyer test. RESULTS: In acute cases, recovery was more related to LRP activity in the contralesional hemisphere (73%), whereas lateralization was equal in chronic cases; 50% in either group. LRP amplitude was higher in the contralesional hemisphere (p = 0.02). Functional recovery assessed by the Fugl Meyer test (FM) was similar whether recovery was ipsi- or contralesional. CONCLUSIONS: Early after stroke, motor recovery is more likely to involve compensatory activity in the contralesional hemisphere, while in the chronic phase, the ipsilesional hemisphere may recover its function and become more active. Further research is needed to verify if the technique mentioned in our study could be used to guide customized NIBS protocols tailoring the optimal site and parameters for each patient.

Peripheral magnetic theta burst stimulation to muscles can effectively reduce spasticity: a randomized controlled trial.

BACKGROUND: Spasticity is a common complication of many neurological diseases and despite contributing much disability; the available therapeutic options are limited. Peripheral magnetic stimulation is one promising option. In this study, we investigated whether peripheral intermittent theta burst stimulation (piTBS) will reduce spasticity when applied directly on spastic muscles. METHODS: In this sham-controlled study, eight successive sessions of piTBS were applied directly to spastic muscles with supra threshold intensity. Assessment was done by modified Ashworth scale (mAS) and estimated Botulinum toxin dose (eBTD) at baseline and after the 8th session in both active and sham groups. RESULTS: A total of 120 spastic muscles of 36 patients were included in the analysis. Significant reduction of mAS and eBTD was found in the active compared to sham group (p < 0.001). The difference in mAS was also significant when tested in upper limb and lower limb subgroups. The degree of reduction in mAS was positively correlated with the baseline scores in the active group. CONCLUSION: piTBS could be a promising method to reduce spasticity and eBTD. It consumes less time than standard high frequency protocols without compromising treatment efficacy. TRIAL REGISTRATION: Clinical trial registry number: PACTR202009622405087. Retrospectively Registered 14th September, 2020.

Changing the Landscape of Stroke in Egypt.

Egypt, a low-middle-income country, is the most populated nation in the Middle East with a high overall crude prevalence rate of stroke (963/100,000 inhabitants), accounting for 6.4% of all deaths. In this article, we discuss how, through a corrective plan, we could change the landscape of stroke services in Egypt, in a relatively short time, raising thrombolysis rate from <1% to 12.3%, with shortening of door-to-needle time. We could build a database that now exceeds 5,000 patients, our centers received international accreditation and several awards, and we developed tele-stroke service.

Door to Needle Count Down: A 3-Years Experience in an Egyptian University Stroke Center.

BACKGROUND: The purpose of this study is to share our experience in changing hospital strategies to achieve rapid thrombolysis in acute ischemic stroke (AIS) patients in 2 university stroke centers. Rapid reperfusion by shortening door to needle time (DTN) reduces morbidity and mortality for patients with AIS. Our aim is to evaluate the effect of applying certain logistic strategies to reduce DTN for thrombolysis and its impact on clinical outcome. METHODS: In this retrospective registry-based observational study from the SITS-ISTR Dataset, we studied AIS patients admitted to 2 stroke centers in Ain Shams University over 3 successive years from 2016 till 2018. We analyzed change of DTN and outcome at 3 months by modified Rankin scale over these 3 years. RESULTS: By the end of the 3 year period there was a 6.1% increase in number of patients receiving thrombolysis. There was a significant decrease of median DTN by 41%, and increase in percentage of patients receiving recombinant tissue plasminogen activator within a shorter DTN. Also, the number of patients with a favorable outcome (modified Rankin scale≤2) increased by 23.3%. There was insignificant difference regarding mortality rate. CONCLUSION: Applying a goal-directed corrective strategy to improve quality of service can, in a short time, reduce DTN and improve patient outcome.

Pre-hospital causes for delayed arrival in acute ischemic stroke before and during the COVID-19 pandemic: A study at two stroke centers in Egypt.

BACKGROUND: In the current study we investigated the causes of pre-hospital delay as this can compromise the patient's chance to receive thrombolytic therapy and thus impact stroke outcome. METHODS: We surveyed 254 patients regarding reasons for delayed and early arrival to hospital after acute ischemic stroke. The survey was performed over five months, spanning a period pre- and during COVID-19 (between December 7, 2019 and May 10, 2020). RESULTS: A total of 71.2% of patients arrived beyond four hours of onset of ischemic stroke. The commonest cause for delay pre-Covid-19 was receiving treatment in a non-stroke hospital, while that during COVID-19 was fear of infection and lock down issues. Not realizing the urgency of the condition and stroke during sleep were common in both periods. Early arrival because of the patient's previous experience with stroke accounted for approximately 25% of cases in both periods. The effect of media was more evident during COVID-19, accounting for 47.7% of cases. CONCLUSION: Pre-hospital delay secondary to misperception of the urgency of stroke and management in a non-stroke hospital reflect the lack of awareness among the public and medical staff. This concept is emphasized by early arrival secondary to previous experience with stroke and the pronounced effect of media in the time of COVID-19.

Ondine's curse, a fatal infarction diagnosed by polysomnography and saved by ventilation: a case report.

BACKGROUND: Lateral medullary syndrome causing Ondine's curse is a rare yet fatal brainstem infarction. Any patient presenting with lateral medulla infarction ought to be well observed and a polysomnography must be ordered for him. CASE PRESENTATION: A patient presenting with Ondine's curse is dealt with through polysomnography as a diagnostic procedure that was followed by tracheostomy with portable ventilator and cardiac pacemaker as a therapeutic maneuver which ultimately preserved his life. CONCLUSION: Lateral medullary syndrome infarct could be a life-threatening stroke if not diagnosed and managed properly.

Borderzone Infarction and Small Vessel Disease in a Sample of Egyptian Stroke Patients: Differences and Similarities.

BACKGROUND: The anatomical location of white matter hyperintense lesions in small vessel disease are apparently similar to those of borderzone infarction. The objective of this study is to find clinical and radiological points of differentiation between the two vascular disorders in a sample of Egyptian patients which might have an impact on primary and secondary prevention. METHODS: Ischemic stroke patients with white matter lesions were categorized into two groups: small vessel disease and borderzone infarctions. NIHSS was done on admission. Risk factor profile was reported, and investigations done including: HbA1C, lipid profile, CRP, ECG, echocardiography, carotid duplex, brain MRI, MRA and MR perfusion study. RESULTS: 46 patients completed the study, 29 with SVD and 17 with BZI. Smoking, hypertension and recurrent stroke were more common in borderzone infarctions, but only diabetes was significantly higher (p = 0.047). Limb shaking was more observed in borderzone infarctions (p = 0.049). Radiologically: lacunar pattern was observed more in small vessel disease, while rosary pattern was more in borderzone infarctions (p = 0.04). FLAIR symmetrical lesions and microbleeds were more significant in small vessel disease (p = <0.001; 0.048, respectively). Perfusion study time to peak denoted evidence of significant hypoperfusion in all regions of interest in borderzone infarctions. CONCLUSION: Limb shaking, retinal claudication or syncope, with MRI showing rosary pattern of white matter hyperintensity, few microbleeds and markedly impaired perfusion favor the diagnosis of borderzone infarctions. On the other hand, presence of lacunae, FLAIR showing symmetrical WMH and microbleeds with minimal or no perfusion deficit suggests the diagnosis of small vessel disease.

Navigated perilesional transcranial magnetic stimulation can improve post-stroke visual field defect: A double-blind sham-controlled study.

BACKGROUND: Visual field defects (VFD) usually do not show improvement beyond 12 weeks from their onset. It has been shown that repetitive presentation of a stimulus to areas of residual vision in cases of visual field defect can improve vision. The counterpart of these areas in the brain are the partially damaged brain regions at the perilesional areas where plasticity can be enhanced. OBJECTIVE: We aimed to study the effect of navigated repetitive transcranial magnetic stimulation (rTMS) applied to perilesional areas on the recovery of patients with cortical VFD. METHODS: Thirty-two patients with cortical VFD secondary to stroke of more than 3 months duration received 16 sessions of either active or sham high frequency navigated perilesional rTMS. Automated perimetry and visual functioning questionnaire (VFQ-25) were performed at baseline and after completion of the sessions. RESULTS: The active group showed significant improvement after intervention, compared to the sham group, in both mean deviation (MD), visual field index (VFI) and in the VFQ-25 scores. CONCLUSIONS: Navigated rTMS is a new treatment option for post-stroke VFD as it can selectively stimulate areas of residual vision around the infarcted tissue, improving the threshold of visual stimulus detection which could be used alone or in combination with existing therapies.

Factors related to time of stroke onset versus time of hospital arrival: A SITS registry-based study in an Egyptian stroke center.

BACKGROUND: High-quality data on time of stroke onset and time of hospital arrival is required for proper evaluation of points of delay that might hinder access to medical care after the onset of stroke symptoms. PURPOSE: Based on (SITS Dataset) in Egyptian stroke patients, we aimed to explore factors related to time of onset versus time of hospital arrival for acute ischemic stroke (AIS). MATERIAL AND METHODS: We included 1,450 AIS patients from two stroke centers of Ain Shams University, Cairo, Egypt. We divided the day to four quarters and evaluated relationship between different factors and time of stroke onset and time of hospital arrival. The factors included: age, sex, duration from stroke onset to hospital arrival, type of management, type of stroke (TOAST classification), National Institute of Health Stroke Scale (NIHSS) on admission and favorable outcome modified Rankin Scale (mRS ≤2). RESULTS: Pre-hospital: highest stroke incidence was in the first and fourth quarters. There was no significant difference in the mean age, sex, type of stroke in relation to time of onset. NIHSS was significantly less in onset in third quarter of the day. Percentage of patients who received thrombolytic therapy was higher with onset in the first 2 quarters of the day (p = <0.001). In-hospital: there was no difference in percentage of patients who received thrombolytic therapy nor in outcome across 4 quarters of arrival to hospital. CONCLUSION: Pre-hospital factors still need adjustment to improve percentage of thrombolysis, while in-hospital factors showed consistent performance.

A case series of ischemic stroke with coronavirus disease 2019 in two Egyptian centers.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel virus that has been reported to have various neurological manifestations. Cerebrovascular disorders have been encountered as a coronavirus disease 2019 (COVID-19) presentation in our center during the pandemic. CASE PRESENTATION: We are presenting 10 cases with cerebrovascular manifestations after having COVID-19 few days prior to stroke. CONCLUSION: Cerebrovascular manifestations can occur in association with COVID-19 and may have significant implications on prognosis and management.

Urban Versus Rural Egypt: Stroke Risk Factors and Clinical Profile: Cross-Sectional Observational Study.

BACKGROUND: Egypt is a densely populated country with living habits and health care services that differ from urban to rural regions. We aimed to study how characteristics of stroke vary among these regions. METHODS: This is a cross-sectional observational study of ischemic stroke, thus hemorrhagic and venous strokes were excluded. A total of 1475 ischemic stroke patients were recruited for analysis from a tertiary hospital in Cairo representing urban area and from a secondary care hospital in Suhag representing rural region. RESULTS: Analysis was done for 1143 ischemic stroke patients from urban and 332 from rural area. Onset to door was shorter in urban. Urban patients showed an older age and higher prevalence of hypertension and diabetes (65.9%, 48.6% respectively), while rural patients were characterized by female preponderance (51.5%), more dyslipidemia, smoking 44.6%, stroke in young 20.5%, atrial fibrillation 23.8% % and recurrent stroke 44.3%. Rural cases showed a severer deficit at onset and poorer outcome. CONCLUSION: Vascular risk factors, stroke type, and presentation tend to differ in Egypt according to the geographic distribution whether urban or rural. Studying patterns of such difference may aid in planning specific targeted preventive and therapeutic strategies for stroke in urban and rural Egypt.

MRI can Predict the Response to Therapeutic Repetitive Transcranial Magnetic Stimulation (rTMS) in Stroke Patients.

BACKGROUND: Previous studies suggest that purposeful modulation of excitability by up regulation in primary motor area (M1) in the lesioned hemisphere or down regulation of excitability in M1 intact hemisphere can influence function in the paretic hand.. OBJECTIVES: 1- To determine if magnetic resonance imaging (MRI) delineation of lesion has an impact on the modality and site of rTMS stimulation, and 2- To determine whether MRI can predict the degree of recovery of motor function after rTMS treatment. METHODS: A total of 60 ischemic stroke patients were recruited. Physical examination, mini mental state examination, activities of daily living assessment, motor subscale of the activity index (AI) and fine hand movement assessment were performed initially and then 2 weeks later (after the end of therapeutic course), then at 4, 8, and 12 weeks. MRI was performed for all patients and used to localize the site and extent of lesion. The patients were divided to 3 group consisting of 20 patients each: group 1 received repetitive rTMS 5hz at 90% motor threshold for 2.5min on the infarcted hemisphere, group 2 received rTMS 1hz at 110% motor threshold for 2.5min on the intact hemisphere, and group 3 received sham stimulation. All patients received standard physical therapy following each rTMS session. RESULTS: Patients with total anterior circulation stroke demonstrated on MRI showed no significant improvement when compared to those with partial anterior circulation, lacunar or posterior circulation strokes. The patients with cortical strokes experienced less improvement when compared with those with subcortical strokes especially with 1 hz stimulation to intact hemisphere. CONCLUSION: MRI can help predict the response to rTMS for stroke rehabilitation and assist the clinician choose the mode and site of rTMS application.