Cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia in middle-income countries.

BACKGROUND: Adenovirus-based COVID-19 vaccines are extensively used in low- and middle-income countries (LMICs). Remarkably, cases of cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) have rarely been reported from LMICs. AIMS: We studied the frequency, manifestations, treatment, and outcomes of CVST-VITT in LMICs. METHODS: We report data from an international registry on CVST after COVID-19 vaccination. VITT was classified according to the Pavord criteria. We compared CVST-VITT cases from LMICs to cases from high-income countries (HICs). RESULTS: Until August 2022, 228 CVST cases were reported, of which 63 were from LMICs (all middle-income countries [MICs]: Brazil, China, India, Iran, Mexico, Pakistan, Turkey). Of these 63, 32 (51%) met the VITT criteria, compared to 103 of 165 (62%) from HICs. Only 5 of the 32 (16%) CVST-VITT cases from MICs had definite VITT, mostly because anti-platelet factor 4 antibodies were often not tested. The median age was 26 (interquartile range [IQR] 20-37) versus 47 (IQR 32-58) years, and the proportion of women was 25 of 32 (78%) versus 77 of 103 (75%) in MICs versus HICs, respectively. Patients from MICs were diagnosed later than patients from HICs (1/32 [3%] vs. 65/103 [63%] diagnosed before May 2021). Clinical manifestations, including intracranial hemorrhage, were largely similar as was intravenous immunoglobulin use. In-hospital mortality was lower in MICs (7/31 [23%, 95% confidence interval (CI) 11-40]) than in HICs (44/102 [43%, 95% CI 34-53], p = 0.039). CONCLUSIONS: The number of CVST-VITT cases reported from LMICs was small despite the widespread use of adenoviral vaccines. Clinical manifestations and treatment of CVST-VITT cases were largely similar in MICs and HICs, while mortality was lower in patients from MICs.

Comparative Study of Cerebral Venous Thrombosis-risk factors, clinical course and outcome in Subjects with and without Covid-19 infection.

Background/ Objective: Cerebral venous thrombosis (CVT) has been increasingly reported in patients with COVID-19. Most published literature is descriptive and focuses only on CVT in COVID-19 patients. The objective of our study is to compare CVT patients' characteristics with and without an associated COVID-19 infection. MATERIALS AND METHODS: This is a retrospective cross-sectional study. All adult patients with a confirmed diagnosis of CVT admitted to our hospital over a period of 30 months, from January 2019 to June 2021, were included. They were further divided into two groups, with and without COVID-19 infection. RESULTS: A total of 115 CVT patients were included, 93 in non-COVID CVT and 22 in COVID CVT group. COVID-CVT patients were male predominant and of older age, with longer hospital stay, and higher inpatient mortality. COVID CVT patients presented with a higher frequency of headache (82% vs. 63%), seizures (64% vs. 37%, p=0.03), hemiparesis (41% vs. 24%), and visual changes (36% vs. 19%) as compared to non-COVID CVT patients. Venogram showed a higher frequency of superior sagittal sinus (64% vs. 42%) and internal jugular vein (23% vs. 12%) involvement in the COVID CVT cohort. More than 90% of patients in both groups received therapeutic anticoagulation. Mortality rates were higher in COVID CVT group (18% vs. 11%). CONCLUSION: COVID-CVT patients were male predominant and of older age, with higher hospital stay, and higher inpatient mortality as compared to non-covid CVT patients.

Air Pollution and Cerebrovascular Disorders with Special Reference to Asia: An Overview.

Background: Among the primary environmental issues affecting global health, air pollution is considered the leading cause of concern. Globally, around 800,000 deaths were attributed to air pollution according to WHO. Evidence suggests that there has been a strong association of air pollution with stroke. Approximately, 25% of stroke mortality was due to air pollution according to a study in 2013. Objective: The aim of this review was to analyze the association between stroke, intracerebral hemorrhage, and subarachnoid hemorrhage and air pollution and its burden globally with a special focus on South Asia along with its association with the COVID-19 pandemic. Results: There is growing research data linking air pollution to cardiovascular disorders including stroke. Short-term and long-term air pollution exposures have been shown to increase stroke incidence in epidemiological data. Air pollution, both gaseous and particle, show a strong and tight temporal relationship with stroke hospitalizations and death. The link between ICH and SAH to air pollution is less strong and less well studied as compared to ischemic stroke. Stroke and air pollution both are highly prevalent in South Asia. It is possible that the high prevalence of stroke in south Asia may be linked to the high frequency of air pollution in addition to other conventional risk factors. Decreased stroke admissions and mortality and reduced cardiovascular mortality reported during coronavirus disease 2019 (COVID) lockdown may be attributable to decreased levels of air pollution. Conclusion: Even though air pollution poses a significant threat to human health, a great number of countries still fail to achieve internationally agreed air quality standards. Air pollution should be recognized among the most significant controllable risk factors for cardiovascular and cerebrovascular disease prevention and treatment.

COVID-19 independently predicts poor outcomes in Acute Ischemic Stroke- Insights from a multicenter study from Pakistan and United Arab Emirates.

BACKGROUND: Ischemic stroke associated with coronavirus 2019 (COVID-19) has been well recognized by now. Few studies have compared COVID related versus unrelated strokes. We intend to report on a large group of Asian patients from two countries and compare COVID with non-COVID strokes admitted during the same time period. METHODS: Consecutive cases of acute ischemic stroke either presenting or developing, between March 2020 and December 2021 in four tertiary care hospitals (1 in Dubai, UAE and 3 in Karachi, Pakistan) and testing positive for COVID-19 were included in the study. Patients admitted with ischemic stroke during the same time period and who tested negative for COVID-19 were also randomly selected from the four hospitals. All data was collected from the medical records of the patients and recorded on a standard questionnaire before it was entered in SPSS version 21 for analysis. RESULTS: There were 139 COVID positive and 271 COVID negative patients with acute ischemic stroke included in the current study. There were significantly more males (80.6% vs 64.9%, p=0.001) and more large vessel strokes in the COVID positive group (41% vs 21.8%, p<0.001). Being COVID positive was an independent predictor of poor outcome at discharge, defined as a modified Rankin score of 3-6 (OR 3.87, 95% CI 2.21-6.77) after adjusting for country, age, sex, vascular comorbid conditions and stroke subtype. CONCLUSIONS: In this largest series of patients with COVID related strokes from Asia, COVID-19 was an independent predictor of poor outcomes at discharge after adjusting for other variables.

Spectrum of EEG Abnormalities in COVID-19 Patients.

PURPOSE: Neurologic involvement is commonly reported in coronavirus disease (COVID-19) patients. The published literature regarding the COVID-19-related neurophysiological findings, including the EEG findings, is still quite limited. The objective of this study was to evaluate the EEG findings in patients with a COVID-19 infection and look for a possible correlations and prognosis. METHODS: This is an inpatient hospital-based retrospective observational study. All admitted COVID-19 patients undergoing an EEG study between January 1, 2020 and June 30, 2021 were included in this study. EEG was ordered by the primary intensive care physician or a neurologist taking part in the clinical care of patients. RESULTS: Sixty-six EEG studies in 57 patients were included. Mean age was 62.2 ± 16.3 years with male predominance (65%). Encephalopathy (70%) was the most common indication for an EEG. Background EEG abnormalities were seen in most of the patients (92.4%) with severe abnormalities correlating with the prognosis of the patient. Epileptiform discharges were only seen in 7.5% of the EEGs, with majority of the discharges arising from the frontal region. Mortality reported was high (47%). CONCLUSIONS: Nonspecific diffuse background EEG abnormalities are commonly seen in COVID-19 patients. Epileptiform discharges are less common but mostly originate from frontal region. Most of these patients also had an abnormal neuroimaging. The significance of this peculiar finding needs further research. SIGNIFICANCE: Nonspecific background EEG changes are common in COVID-19 patients. Among epileptiform discharges, focal epileptiform discharges arising from the frontal region were common, usually associated with an abnormal neuroimaging.

First Report of Cerebral Venous Thrombosis Following Inactivated-Virus Covid Vaccination (Sinopharm and Sinovac).

Cerebral venous thrombosis (CVT) is an uncommon cerebrovascular disease, which has been reported with covid infection as well as covid vaccines, particularly AstraZeneca and Janssen vaccines. We present four consecutive cases of CVT after receiving either Sinopharm or Sinovac vaccine, both of which are composed of an inactivated-virus. All the patients recovered well with anticoagulation and discharged with a good functional outcome. This is the first case series reporting CVT following the administration of these vaccines.

Exploring the Relationship Between Air Quality and Ischemic Stroke Admissions During the COVID-19 Pandemic.

OBJECTIVES: Amongst all the global catastrophe due to Coronavirus disease 2019, a significant bright spot is a reduction in air pollution as countries undergo lockdowns to limit the spread of infection. Another reduction that has been reported is in the number of strokes presenting to hospitals, despite the virus implicated in causing a hypercoagulable state. Acute exposure to air pollution has been linked to increase in stroke incidence and the improvement in air quality may be responsible for the decrease in stroke presentations. MATERIALS AND METHODS: To explore this hypothesis, we compared the air quality index (AQI) of Karachi, the largest cosmopolitan city of Pakistan, during the lockdown period in 2020 to the same period in the previous year. RESULTS: We found a significant drop in AQI depicting an improvement in air quality. Simultaneously, we identified a drop in number of stroke admissions to less than half from 2019 to 2020 at one of the largest tertiary care hospitals of the city, during this period of interest. CONCLUSION: We hypothesize that one important reason for this drop in stroke admissions, may be an actual reduction in stroke incidence brought about by an improvement in air quality.

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 Care during the COVID-19 Pandemic: International Expert Panel Review.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has placed a tremendous strain on healthcare services. This study, prepared by a large international panel of stroke experts, assesses the rapidly growing research and personal experience with COVID-19 stroke and offers recommendations for stroke management in this challenging new setting: modifications needed for prehospital emergency rescue and hyperacute care; inpatient intensive or stroke units; posthospitalization rehabilitation; follow-up including at-risk family and community; and multispecialty departmental developments in the allied professions. SUMMARY: The severe acute respiratory syndrome coronavirus 2 uses spike proteins binding to tissue angiotensin-converting enzyme (ACE)-2 receptors, most often through the respiratory system by virus inhalation and thence to other susceptible organ systems, leading to COVID-19. Clinicians facing the many etiologies for stroke have been sobered by the unusual incidence of combined etiologies and presentations, prominent among them are vasculitis, cardiomyopathy, hypercoagulable state, and endothelial dysfunction. International standards of acute stroke management remain in force, but COVID-19 adds the burdens of personal protections for the patient, rescue, and hospital staff and for some even into the postdischarge phase. For pending COVID-19 determination and also for those shown to be COVID-19 affected, strict infection control is needed at all times to reduce spread of infection and to protect healthcare staff, using the wealth of well-described methods. For COVID-19 patients with stroke, thrombolysis and thrombectomy should be continued, and the usual early management of hypertension applies, save that recent work suggests continuing ACE inhibitors and ARBs. Prothrombotic states, some acute and severe, encourage prophylactic LMWH unless bleeding risk is high. COVID-19-related cardiomyopathy adds risk of cardioembolic stroke, where heparin or warfarin may be preferable, with experience accumulating with DOACs. As ever, arteritis can prove a difficult diagnosis, especially if not obvious on the acute angiogram done for clot extraction. This field is under rapid development and may generate management recommendations which are as yet unsettled, even undiscovered. Beyond the acute management phase, COVID-19-related stroke also forces rehabilitation services to use protective precautions. As with all stroke patients, health workers should be aware of symptoms of depression, anxiety, insomnia, and/or distress developing in their patients and caregivers. Postdischarge outpatient care currently includes continued secondary prevention measures. Although hoping a COVID-19 stroke patient can be considered cured of the virus, those concerned for contact safety can take comfort in the increasing use of telemedicine, which is itself a growing source of patient-physician contacts. Many online resources are available to patients and physicians. Like prior challenges, stroke care teams will also overcome this one. Key Messages: Evidence-based stroke management should continue to be provided throughout the patient care journey, while strict infection control measures are enforced.

Neurological manifestations of COVID-19.

Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) has turned out to be a formidable pandemic. Upcoming evidence from confirmed cases of COVID-19 suggests an anticipated incursion of patients with neurological manifestations in the weeks to come. An expression of the angiotensin-converting enzyme 2 (ACE 2), the cellular receptor for SARS-CoV-2 over the glial cells and neurons have made the brain a potential target. Neurotoxicity may occur as a result of direct, indirect and post-infectious complications. Attention to neurological deficits in COVID-19 is fundamental to ensure appropriate, timely, beneficial management of the affected patients. Most common neurological manifestations seen include dizziness, headache, impaired consciousness, acute cerebrovascular disease, ataxia, and seizures. Anosmia and ageusia have recently been hinted as significant early symptoms in COVID-19. As cases with neurological deficits in COVID-19 emerge, the overall prognosis is yet unknown.

The neurology of COVID-19 revisited: A proposal from the Environmental Neurology Specialty Group of the World Federation of Neurology to implement international neurological registries.

A comprehensive review of the neurological disorders reported during the current COVID-19 pandemic demonstrates that infection with SARS-CoV-2 affects the central nervous system (CNS), the peripheral nervous system (PNS) and the muscle. CNS manifestations include: headache and decreased responsiveness considered initial indicators of potential neurological involvement; anosmia, hyposmia, hypogeusia, and dysgeusia are frequent early symptoms of coronavirus infection. Respiratory failure, the lethal manifestation of COVID-19, responsible for 264,679 deaths worldwide, is probably neurogenic in origin and may result from the viral invasion of cranial nerve I, progressing into rhinencephalon and brainstem respiratory centers. Cerebrovascular disease, in particular large-vessel ischemic strokes, and less frequently cerebral venous thrombosis, intracerebral hemorrhage and subarachnoid hemorrhage, usually occur as part of a thrombotic state induced by viral attachment to ACE2 receptors in endothelium causing widespread endotheliitis, coagulopathy, arterial and venous thromboses. Acute hemorrhagic necrotizing encephalopathy is associated to the cytokine storm. A frontal hypoperfusion syndrome has been identified. There are isolated reports of seizures, encephalopathy, meningitis, encephalitis, and myelitis. The neurological diseases affecting the PNS and muscle in COVID-19 are less frequent and include Guillain-Barré syndrome; Miller Fisher syndrome; polyneuritis cranialis; and rare instances of viral myopathy with rhabdomyolysis. The main conclusion of this review is the pressing need to define the neurology of COVID-19, its frequency, manifestations, neuropathology and pathogenesis. On behalf of the World Federation of Neurology we invite national and regional neurological associations to create local databases to report cases with neurological manifestations observed during the on-going pandemic. International neuroepidemiological collaboration may help define the natural history of this worldwide problem.