Efficacy and Safety of Brivaracetam in Persons With Epilepsy in a Real-World Setting: A Prospective, Non-Interventional Study.

BACKGROUND AND AIM: Epilepsy stands out as one of the most prevalent neurological conditions. Brivaracetam (BRV) is a noteworthy antiseizure medication (ASM) distinguished by its pronounced and selective interaction with the synaptic vesicle protein 2A (SV2A) within the brain. Prior investigations, including regulatory trials, post-marketing assessments, and comparative meta-analyses, have consistently underscored BRV's equivalency in efficacy and superior tolerability when pitted against other antiseizure drugs. This study aimed to evaluate the effectiveness, safety, and acceptability of BRV in treating epileptic patients in the Pakistani population. METHODS: This prospective observational study, conducted in Pakistan from February to December 2022, employed a non-probability consecutive sampling technique. This study included 368 adult patients diagnosed with epilepsy, with a focus on those aged 18 and above experiencing focal seizures. Demographic data, clinical history, seizure types, and epilepsy profiles were recorded. Patients were administered BRV (Brivera; manufactured by Helix Pharma Pvt Ltd., Sindh, Pakistan) monotherapy therapy under physician guidance and followed up for three months. The study assessed changes in seizure frequency, side effects, and drug resistance at baseline, 14th day, and 90th day. Safety aspects were monitored, including documenting any adverse effects associated with BRV therapy. RESULTS: A total of 368 epileptic patients were included in this study, of which 287 (61.3%) were males and 181 (38.7%) were females. The mean age was 32.91±17.11 years. The mean number of seizures at the baseline visit was 5.74±6.21, at 14 days was 2.89±3.84 and at 90 days was 1.73±5.01 (p<0.001). Overall, a more than 50% reduction in seizure episodes was achieved in 178 (56.3%) patients at day 90, and less than 50% reduction in seizure episodes was achieved by 95 (26.8%) patients on Day 14, with a highly significant association between them (p<0.001). Among 316 patients, only 41 (4.4%) of all BRV-treated patients experienced adverse events; Of these 41 patients, 17 (41.7%) reported dizziness and 14(34.2%) reported behavioral issues. CONCLUSIONS: Epileptic patients receiving BRV demonstrated a substantial reduction of greater than 50% seizure episodes at the end of follow-up visits. Moreover, BRV exhibited fewer adverse effects in individuals with epilepsy.

Cerebral Venous Thrombosis Associated with COVID-19 Infection: An Observational, Multicenter Study.

BACKGROUND AND PURPOSE: Coronavirus disease 2019 (CO-VID-19) has an increased propensity for systemic hypercoagulability and thromboembolism. An association with cerebrovascular diseases, especially cerebral venous thrombosis (CVT), has been reported among these patients. The objective of the present study was to identify risk factors for CVT as well as its presentation and outcome in COVID-19 patients. METHODS: This is a multicenter and multinational observational study. Ten centers in 4 countries (Pakistan, Egypt, Singapore, and the United Arab Emirates) participated in this study. The study included patients (aged >18 years) with symptomatic CVT and recent COVID-19 infection. RESULTS: Twenty patients (70% men) were included. Their mean age was 42.4 years, with a male-to-female ratio of 2.3:1. Headache (85%) and seizures (65%) were the common presenting symptoms, with a mean admission Glasgow Coma Scale (GCS) score of 13. CVT was the presenting feature in 13 cases (65%), while 7 patients (35%) developed CVT while being treated for COVID-19 infection. Respiratory symptoms were absent in 45% of the patients. The most common imaging finding was infarction (65%), followed by hemorrhage (20%). The superior sagittal sinus (65%) was the most common site of thrombosis. Acute inflammatory markers were raised, including elevated serum D-dimer (87.5%), erythrocyte sedimentation rate (69%), and C-reactive protein (47%) levels. Homocysteine was elevated in half of the tested cases. The mortality rate was 20% (4 patients). A good functional outcome was seen in the surviving patients, with a mean modified Rankin Scale score at discharge of 1.3. Nine patients (45%) had a modified Rankin Scale score of 0-1 at discharge. CONCLUSION: COVID-19-related CVT is more common among males at older ages when compared to previously reported non-COVID-19-related CVT cases. CVT should be suspected in COVID-19 patients presenting with headache or seizures. Mortality is high, but functional neurological outcome is good among survivors.

Preparedness and impact of COVID 19 infection at tertiary care neurology centers in Pakistan.

OBJECTIVE: We aimed to assess the response and impact of covid 19 pandemic at tertiary care centers in Pakistan especially pertaining to neurological care, facilities and training. METHODS: A pre-tested survey form was sent to 40 neurology tertiary care centers in all the provinces in the country in the first week of July 2020. 33 filled forms were received, out of which 18 were public (government) and 15 were private hospitals. RESULTS: Estimated 1300 HCW (faculty, medical officers, trainees and nurses) work at these 33 participating centers. There were 17 deaths among HCW (1.3%) at ten centers. Sufficient personal protective equipment (PPE) were provided to 158 HCW (12%). 129 (10%)HCW tested positive for COVID 19 at 31 centers including trainees/medical officers (39), consultants (29) and nursing and other staff (61). Due to low neurology admissions, 23/33 hospitals (70%) posted neurology trainees in COVID 19 units to contribute to covid care. Less than 50% hospitals did covid screening PCR before admission to neurology wards. Only 10% hospitals provide training and regular update to HCW. Neurology tele-health services were started for clinically stable patients at 15 (45%) centers. Only 60% neurology training programs were able to start online training. Ongoing research studies and trials focusing neurological manifestations of COVID-19 were done at 10 (30%) centers. Modification of facilities for COVID patients showed that 24(72%) hospitals strictly reduced the number of attendants accompanying patients. Only 10 (30%) centers had neurophysiological tests being conducted on COVID-19 patients. Mental health support services to HCW were provided at 12 (36%) centers. CONCLUSIONS: Among HCW 10% tested positive for covid and 1.3% died. Mental health support services offered for HCW were available in 36% institutions. Neurology training was substantially affected due to low admissions, limited ward rounds and limited availability of online training.

Stroke in the Middle-East and North Africa: A 2-year prospective observational study of stroke characteristics in the region-Results from the Safe Implementation of Treatments in Stroke (SITS)-Middle-East and North African (MENA).

BACKGROUND AND METHODS: Stroke incidence and mortality are reported to have increased in the Middle-East and North African (MENA) countries during the last decade. This was a prospective observational study to examine the baseline characteristics of stroke patients in the MENA region and to compare the MENA vs. the non-MENA stroke cohort in the Safe Implementation of Treatments in Stroke (SITS) International Registry. RESULTS: Of the 13,822 patients with ischemic and hemorrhagic stroke enrolled in the SITS-All Patients Protocol between June 2014 and May 2016, 5897 patients (43%) were recruited in MENA. The median onset-to-door time was 5 h (IQR: 2:20-13:00), National Institutes of Health Stroke Scale (NIHSS) score was 8 (4-13) and age was 65 years (56-76). Hypertension (66%) and diabetes (38%) were the prevailing risk factors; large artery stenosis > 50% (25.3%) and lacunar strokes (24.1%) were the most common ischemic stroke etiologies. In comparison, non-MENA countries displayed an onset-to-door time of 5:50 h (2:00-18:45), a median of NIHSS 6 (3-14), and a median age of 66 (56-76), with other large vessel disease and cardiac embolism as the main ischemic stroke etiologies. Hemorrhagic strokes (10%) were less common compared to non-MENA countries (13.9%). In MENA, only a low proportion of patients (21%) was admitted to stroke units. CONCLUSIONS: MENA patients are slightly younger, have a higher prevalence of diabetes and slightly more severe ischemic strokes, commonly of atherosclerotic or microvascular etiology. Admission into stroke units and long-term follow-up need to be improved. It is suspected that cardiac embolism and atrial fibrillation are currently underdiagnosed in MENA countries.

The hyperdense basilar artery sign: a case of locked-in syndrome.

BACKGROUND: Locked-in syndrome, although a notoriously famous clinical entity, the rarity of the condition coupled with the variability of clinical features on acute presentation represents a potential diagnostic pitfall for the emergency physician. CASE: A previously healthy 25-year-old female was brought to our Emergency Department after being found unresponsive. On examination, she was conscious and alert with a Glasgow Coma Score of 9; on neurological examination, the patient was quadriplegic and unable to speak but was able to move her eyes and blink. Non-contrast brain computed tomography (CT) revealed a hyperdense basilar artery, and CT cerebral angiography confirmed basilar artery thrombosis. CONCLUSION: This case highlights the need for a high index of suspicion to make a diagnosis of locked-in syndrome in the Emergency Department, especially in young patients with no apparent risk factors for an ischemic stroke. The hyperdense basilar artery sign is one of the earliest signs on non-contrast CT imaging and may be the only clue to guide further management in a patient with basilar artery occlusion.

Drug resistant neuroleptic malignant syndrome and the role of electroconvulsive therapy.

Neuroleptic malignant syndrome is considered as a rare but potentially fatal complication of neuroleptic medications e.g.,antipsychotics, sedatives and anti emetics. It is characterized by hyperthermia, muscle rigidity, an elevated creatine kinase level and autonomic instability. The syndrome often develops after the start of antipsychotic or a sudden increase in dosage of the neuroleptic medication or in states of dehydration. Treatment is mainly supportive and includes withdrawal of the neuroleptic medication and, possibly, administration of drugs such as dantrolene and bromocriptine. In rare cases where drugs treatment remains ineffective a trial of electroconvulsive therapy is being given. The case presented is a drug resistant case of Neuroleptic Malignant Syndrome where finally electroconvulsive therapy was effective.