Sex differences in cerebral venous sinus thrombosis after adenoviral vaccination against COVID-19.

INTRODUCTION: Cerebral venous sinus thrombosis associated with vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) is a severe disease with high mortality. There are few data on sex differences in CVST-VITT. The aim of our study was to investigate the differences in presentation, treatment, clinical course, complications, and outcome of CVST-VITT between women and men. PATIENTS AND METHODS: We used data from an ongoing international registry on CVST-VITT. VITT was diagnosed according to the Pavord criteria. We compared the characteristics of CVST-VITT in women and men. RESULTS: Of 133 patients with possible, probable, or definite CVST-VITT, 102 (77%) were women. Women were slightly younger [median age 42 (IQR 28-54) vs 45 (28-56)], presented more often with coma (26% vs 10%) and had a lower platelet count at presentation [median (IQR) 50x109/L (28-79) vs 68 (30-125)] than men. The nadir platelet count was lower in women [median (IQR) 34 (19-62) vs 53 (20-92)]. More women received endovascular treatment than men (15% vs 6%). Rates of treatment with intravenous immunoglobulins were similar (63% vs 66%), as were new venous thromboembolic events (14% vs 14%) and major bleeding complications (30% vs 20%). Rates of good functional outcome (modified Rankin Scale 0-2, 42% vs 45%) and in-hospital death (39% vs 41%) did not differ. DISCUSSION AND CONCLUSIONS: Three quarters of CVST-VITT patients in this study were women. Women were more severely affected at presentation, but clinical course and outcome did not differ between women and men. VITT-specific treatments were overall similar, but more women received endovascular treatment.

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.

Risk Factors for Stroke in the Young (18-45 Years): A Case-Control Analysis of INTERSTROKE Data from 32 Countries.

BACKGROUND: It is not clear whether conventional vascular risk factors are responsible for most strokes in patients younger than 45 years of age. Our objective was to evaluate the association of common risk factors with stroke in individuals under 45 years. METHODS: INTERSTROKE was a case-control study carried out in 32 countries between 2007 and 2015. Patients presenting within 5 days of symptom onset of a first stroke were enrolled as cases. Controls were age and sex matched to cases and had no history of stroke. Cases and controls underwent similar evaluations. Odds ratios (ORs) and population attributable risks (PARs) were calculated to determine the association of various risk factors with all stroke, ischemic stroke, and intracranial hemorrhage, for patients 45 years of age or younger. FINDINGS: 1,582 case-control pairs were included in this analysis. The mean age of this cohort was 38.5 years (SD 6.32). Overall, 71% strokes were ischemic. Cardiac causes {OR: 8.42 (95% confidence interval [CI]: 3.01-23.5)}; binge drinking of alcohol (OR: 5.44 [95% CI: 1.81-16.4]); hypertension (OR: 5.41 [95% CI: 3.40-8.58]); ApoB/ApoA1 ratio (OR: 2.74 [95% CI: 1.69-4.46]); psychosocial stress (OR: 2.33 [95% CI: 1.01-5.41]); smoking (OR: 1.85 [95% CI: 1.17-2.94]); and increased waist-to-hip ratio (OR: 1.69 [95% CI: 1.04-2.75]) were the most important risk factors for ischemic stroke in these young cases. For intracerebral hemorrhage, only hypertension (OR: 9.08 [95% CI: 5.46-15.1]) and binge drinking (OR: 4.06 [95% CI: 1.27-13.0]) were significant risk factors. The strength of association and population attributable risk (PAR) for hypertension increased with age (PAR 23.3% in those <35 years of age, 50.7% in 35-45 years of age). INTERPRETATION: Conventional risk factors such as hypertension, smoking, binge drinking of alcohol, central obesity, cardiac causes, dyslipidemia, and psychosocial stress are important risk factors for stroke in those younger than 45 years of age. Hypertension is the most significant risk factor in all age groups and across all regions and both stroke subtypes. These risk factors should be identified and modified in early adulthood to prevent strokes in young individuals.

Multiple sclerosis in Pakistan: Current status and future perspective.

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) which commonly leads to disability. We reviewed articles on MS from Pakistan using PubMed, Google Scholar and Pak Medinet to present different aspects of the disease and the status of disease modifying treatments in Pakistan and South Asia. MS is not as uncommon in Pakistan as it has been previously thought to be. Estimated prevalence of MS in Pakistan may be 10 per 100,000 population. Data suggests that most features of MS found in Pakistan are similar to those found in the West. These features include a female preponderance, mean age of onset in the third decade of life and similar risk factors including viral infections, smoking, and vitamin D deficiency, as well as genetic risk factors. Relapsing-remitting multiple sclerosis (RRMS) is the most common disease pattern seen in Pakistan which is also consistent with data from other regions. Treatment modalities in Pakistan include immunomodulatory and immunosuppressive drugs. In order to improve care for MS patients in Pakistan, it is extremely important to obtain a population-based prevalence of MS in the country and a national MS registry, along with implementing programs for patients' awareness and the training of doctors, especially internists. There are many disease modifying therapies (DMT) available in Pakistan but no data is available on the utilization and impact of these DMTs.

Role of ADC values and ratios of MRI scan in differentiating typical from atypical/anaplastic meningiomas.

Atypical/anaplastic meningiomas are prone to aggressive behaviour which affects treatment planning and prognostication. Our aim was to assess the role of Apparent Diffusion Coefficient (ADC) values of MRI brain in differentiating typical from atypical/anaplastic meningioma. We reviewed 84 typical and 37 atypical/anaplastic meningiomas and compared mean ADC values and ADC ratios of their preoperative MRI brain. At 3 Tesla, mean ADC value for typical meningioma was1.03±0.10x10-3 and 0.63±0.05x10-3 for atypical/anaplastic meningioma. At 1.5 Tesla, mean ADC value for typical meningioma was 1.05±0.11x10-3 and atypical/ anaplastic meningioma was 0.70 ± 0.04x10-3. The mean ADC ratios were 1.08 ± 0.17 and 0.85 ± 0.15 for typical and atypical/anaplastic meningomas respectively. Mean ADC ratios and the mean ADC values of typical and atypical/anaplastic meningiomas were significantly different (p< 0.001). ADC values and ADC ratios have important role in differentiating typical from atypical/anaplastic meningioma and it must be part of the routine preoperative MRI reporting.

Septic cerebral venous sinus thrombosis.

Septic cerebral venous sinus thrombosis, once a common and deadly disease, has fortunately become rare now. Not only that the incidence has fallen significantly after the antibiotic era, the morbidity and mortality has also decreased substantially. Cavernous sinus thrombosis is by far the commonest form of septic cerebral venous sinus thrombosis. Due to its rare occurrence, a lot of current generation clinicians have not encountered the entity in person. Despite all the advances in diagnostic modalities, a high index of clinical suspicion remains the mainstay in prompt diagnosis and management of this potentially lethal condition. Keeping this in view, the authors have reviewed the subject including the old literature and have summarized the current approach to diagnosis and management. Septic cavernous thrombosis is a fulminant disease with dramatic presentation in most cases comprised of fever, periorbital pain and swelling, associated with systemic symptoms and signs. The preceding infection is usually in the central face or paranasal sinuses. The disease rapidly spreads to contralateral side and if remains undiagnosed and untreated can result in severe complications or even death. Prompt diagnosis using radiological imaging in suspected patient, early use of broad spectrum antibiotics, and judicial use of anticoagulation may save the life and prevent disability. Surgery is used only to treat the nidus of infection.

Implications of female sex on stroke risk factors, care, outcome and rehabilitation: an Asian perspective.

BACKGROUND: Stroke affects 16.9 million people annually and the greatest burden of stroke is in low- and middle-income countries, where 69% of all strokes occur. Stroke risk factors, mortality and outcomes differ in developing countries as compared to the developed world. We performed a literature review of 28 articles pertaining to epidemiology of stroke in Asian women, stroke risk factors, gender-related differences, and stroke outcomes. SUMMARY: Asian women differ from women worldwide due to differences in stroke awareness, risk factor profile, stroke subtypes, and social issues that impact stroke care. While Asian men have a higher incidence of stroke as compared to women overall, the long- and short-term outcomes in Asian women tend to be poorer. Both conventional and gender-specific risk factors contribute to stroke risk. Oral contraceptive use and addictions such as tobacco and alcohol are less prevalent among Asian women due to socio cultural differences. There is however, a much higher preponderance of pregnancy-related stroke and cardio-embolic stroke secondary to rheumatic heart disease and heavy use of chewing tobacco. The overall outcome is poor due to poor access to health care and lack of resources. Key Messages: Our review exposed the gaps in our knowledge about stroke risk factors and differences in stroke care provided to Asian women. While there are sociocultural barriers that impede the provision of immediate care to these stroke patients, much needs to be done by way of prevention of recurrent stroke and treatment of risk factors.

Stroke in South Asian countries.

Three of the world's top 10 most populous countries are located in South Asia. The health-care problems of this region are different from those in the developed world, and the rapidly changing socioeconomic scenario, fast-increasing urbanization and longevity, changes in dietary patterns, and decrease in mortality from infectious diseases has made chronic illnesses of old age, such as coronary artery disease and stroke, an important area of focus. This article reviews stroke epidemiology and management issues in four South Asian countries: India, Pakistan, Sri Lanka and Bangladesh. The available literature is limited and mostly hospital-based, and differing study methodologies make direct comparisons difficult. The high prevalence of traditional risk factors, including hypertension, diabetes, dyslipidaemia and smoking, in these countries is alarming, and several nontraditional risk factors, such as water-pipe use, desi ghee, chewable tobacco, and infectious causes of stroke, are understudied. Access to tertiary stroke care is limited, and the use of tissue plasminogen activator is scarce. In addition, public and caregiver awareness of stroke risk factors and management is disappointing, and the interest of governments and policy makers in stroke is suboptimal. Interventions to reduce stroke burden and stroke-related mortality in South Asia should have a substantial impact at the global level.

A descriptive study to find possible correlation between MRI findings of pituitary gland and serum prolactin level.

OBJECTIVE: To explore equation, if any, between findings of magnetic resonance imaging of pituitary gland and serum prolactin level. METHODS: The retrospective, descriptive study was conducted at the Department of Radiology, Aga Khan University Hospital, Karachi, and related to patients' records from April 19, 2006 to April 23, 2009. Seventy patients underwent magnetic resonance imaging of brain for pituitary gland. Inclusion criteria were all patients referred with relevant clinical symptoms or deranged serum prolactin level. Patients who were claustrophobic or had a pacemaker, aneurysm clip, metallic foreign body in the orbit or with no laboratory investigation were excluded from the study. SPSS 19 was used for statistical analysis. RESULTS: Of the 70 patients, normal imaging was noted in 29 (41.4%) patients. Out of these, 18 (62.06%) patients had normal and 11 (37.93%) had raised serum prolactin levels. Microadenoma was found in 23 (32.8%) patients. Out of these, 10 (42.47%) had normal and 13 (56.52%) had raised prolactin levels. Macroadenoma was found in 16 (22.8 %). Out of these, 8 (50%) had normal and 8 (50%) had raised prolactin levels. Pituitary cyst was located in 2 (2.8 %) patients. Out of these, 1 (50%) had normal and 1 (50%) had raised serum prolactin levels. CONCLUSION: Magnetic resonance imaging of pituitary gland was not associated with serum prolactin levels in patients with clinical suspicion of pituitary abnormality. Therefore, regular monitoring of serum prolactin is suggested.

Reducing transfusion-associated malaria in Pakistan: an algorithmic approach.

Blood transfusions represent a small but significant source of malaria transmission. Most blood banks rely solely on donor questioning to exclude malaria patients from donating blood. No guidelines exist for in vitro screening of donor blood for malaria in endemic areas. Possible laboratory screening techniques include: microscopy; enzyme-linked immunosorbent assay (ELISA) antibody testing; polymerase chain reaction (PCR) testing; and rapid diagnostic antigen tests. However, all these modalities have diagnostic limitations. Based on a best evidence review, we present recommendations using an algorithmic approach to blood screening for malaria in Pakistan. This algorithm considers regional endemicity for malaria, as well as a detailed donor history, in order to decide whether donor blood should be tested with rapid antigen testing. We hope this algorithm will assist in the development of future national guidelines for screening blood for malaria that will reduce the risk of blood-borne transmission.

Haemorrhagic strokes in pregnancy and puerperium.

There is an increased risk of strokes in pregnancy and puerperium. Intracranial haemorrhage is the rarer of the two stroke subtypes but carries a greater morbidity and mortality for both the mother and the child. This review highlights the causes of pregnancy-related intracranial haemorrhage and its management. The incidence varies from region to region with the highest being reported from China and Taiwan. Majority of these haemorrhages are secondary to hypertensive disorders of pregnancy with smaller proportions related to aneurysm and arteriovenous malformation rupture. A small but important contributor is cortical venous thrombosis which, although predominantly gives rise to ischaemic lesions, may lead to parenchymal haemorrhages as well. Presentation is usually with headaches or seizures, with or without focal deficits. Diagnosis requires brain imaging with computerized tomography or magnetic resonance imaging, and the necessity of investigation when this diagnosis is suspected supersedes the small risk of fetal malformation. Management follows the general management principles for intracranial haemorrhage management. Blood pressures need to be strictly monitored and medicines used for controlling them may differ slightly due to teratogenic effects. For preeclampsia, early but safe delivery is the best treatment. For cortical venous thrombosis, low-molecular-weight heparin is the preferred agent. Aneurysms and vascular malformations need to be definitively treated to prevent re-bleed and this can be achieved through surgical or endovascular procedures. The timing of surgery depends on neurosurgical considerations. However, the timing and mode of delivery are governed by obstetric factors. Risk of future haemorrhage depends on whether the underlying aetiology can be and has been definitively treated.

Growing burden of stroke in Pakistan: a review of progress and limitations.

Stroke rates in middle-aged people are five to ten times higher in Pakistan, India, Russia, China, and Brazil, compared with the United Kingdom or United States. South Asia is home to 20% of the world's population and has one of the highest burdens of cardiovascular disease in the world. With an aging population, there is an expected increase in the number of stroke cases and a corresponding increase in the burden of stroke in developing countries including South Asian countries like Pakistan. Limited data from prior studies in developing countries indicate that stroke epidemiology differs between these and Western countries. These differences include a higher incidence of stroke at younger ages, a higher prevalence of hemorrhagic stroke, and higher age-specific prevalence rates of stroke in women. The reasons for these differences in stroke epidemiology in developing countries are not clear. This may be explained by higher prevalence of established stroke risk factors, or potential nontraditional risk factors such as water pipe smoking, use of daldaghee or naswaar, and paan chewing; hepatitis and rheumatic heart disease may also contribute to these differences. Acute and long-term stroke treatment has shown limited progress in Pakistan like other developing countries because of poor awareness of patients and general physician on stroke symptomatology, management of stroke risk factors, lack of specialized stroke units in the country, very low utilization of thrombolytic therapy because of financial constraints and, above all, poor knowledge of physicians on the role of rehabilitation and its different aspects in the management of post stroke disability.

Atrial myxoma: a rare cause of cardioembolic stroke.

The authors present the case of a 45-year-old lady who presented to the emergency department with sudden onset of right hemiparesis, numbness, dysarthria, dysmetria, left upper motor neuron facial palsy and left extensor plantar. Initial laboratory investigations, ECG and MR angiography were normal. MRI brain revealed multiple ischaemic strokes in middle cerebral artery and posterior cerebral artery territory. Transthoracic echocardiography revealed large mobile mass in left atrium which was resected and the patient remained well postoperatively. Anticoagulants do not play any protective role making resection as the only effective treatment.

Knowledge gaps in stroke care: results of a survey of family physicians in Pakistan.

Family physicians play a pivotal role in stroke prevention (primary and secondary) and early management of stroke in developing countries. The objective of this study was to evaluate whether Pakistani family physicians' approach to stroke prevention and management was in accordance with established international guidelines. This was a cross-sectional survey of randomly selected family physicians in Pakistan, conducted in 2007. A total of 588 family physicians participated in the study. The data reveal that 88% of the physicians are aware of at least one of the 5 major symptoms of stroke, but only 46% are able to correctly idenitfy all 5 symptoms; 93% of the physicians check blood pressure in their adult patients regularly, and 63% use a cutoff of 140/90 mm Hg to start antihypertensive therapy in routine clinical practice; 90% ask their patients about cigarette smoking or tobacco use, but only 64% regularly advise their patients to quit smoking; 75% do not routinely check cholesterol levels in their patients; 36% treat patients with stroke by themselves, whereas 64% prefer to refer these patients to a specialist or hospital; 57% use intravenous or sublingual antihypertensive medications in patients with acute stroke with blood pressure >160/100 mm Hg; and 95% use antiplatelet agents for stroke prevention, with 70% using aspirin and 28% using clopidogrel as first-line antiplatelet therapy. These data indicate a substantial gap between international guidelines and Pakistani family physicians' management of stroke patients. There is an urgent need for stroke-related continuing medical education to propagate stroke management guidelines.

Ischemic stroke in young Asian women: risk factors, subtypes and outcome.

BACKGROUND AND OBJECTIVE: The objective of our study was to describe risk factors, mechanisms and outcome of young Asian women with ischemic stroke. METHODS: Twelve tertiary-care centers in 8 Asian countries participated. Women aged 15-45 years were included if they had an ischemic stroke supported by neuroimaging. Data on age, risk factor history, stroke mechanism and discharge status were collected. RESULTS: A total of 958 subjects were included, their mean age was 34 years. Large-vessel thrombosis comprised 24%, cerebral venous thrombosis 21%, cardioembolism 19% and small-vessel thrombosis 15%. The stroke risk factors included hypertension (29%), diabetes (14%), pregnancy (11%), valvular heart disease (10%) and cigarette smoking (3%). Anemia was found in 42%, and mortality was 4%; at discharge, 17% had modified Rankin score (mRS) >4 and 83% mRS 0-3. CONCLUSION: Unlike among Caucasians, large-vessel thrombosis, cerebral venous thrombosis and cardioembolism are common among young Asian women with stroke. A high proportion are pregnancy-related. More studies are needed.

Controversies of treatment modalities for cerebral venous thrombosis.

Cerebral vein thrombosis has been well recognized for nearly two centuries. However, therapeutic options for the condition are limited due to lack of large randomized trials. The various modalities reportedly used include antiplatelets, anticoagulation, fibrinolysis, and mechanical thrombectomy. Of these, antiplatelets are the least studied, and there are only anecdotal reports of aspirin use. Anticoagulation is the most widely used and accepted modality with favorable outcomes documented in two randomized controlled trials. Various fibrinolytic agents have also been tried. Local infusions have shown more promise compared to systemic agents. Similarly, mechanical thrombectomy has been used to augment the effects of chemical thrombolysis. However, in the absence of randomized controlled trials; there is no concrete evidence of the safety and efficacy of either of these modalities. Limited study series disclosed that decompression surgery in malignant CVT can be life saving and provides good neurological outcome in some cases. Conclusion. Overall therapeutics for CVT need larger randomized controlled trials. Anticoagulaion with heparin is the only modality with a reasonable evidence to support its use in CVT. Endovascular thrombolysis and mechanical thrombectomy are reserved for selected cases who fail anticoagulation and decompression surgery for malignant CVT with impending herniation.

Preoperative antifungal therapy may improve survival in patients with Aspergillus brain abscess.

OBJECTIVE: The objective of this study was to determine if the preoperative use of antifungal therapy positively influences clinical outcome in patients with Aspergillus brain abscess. METHODS: We studied 25 patients with confirmed diagnosis of cerebral aspergillosis. We compared baseline characteristics and outcomes of patients treated with either amphotericin B or itraconazole either pre-operatively (n=11) or post-operatively (n=14) at a tertiary care hospital in Karachi. RESULTS: Twenty-five patients were included in the study. Cerebral aspergillosis was largely a disease of immune competent people (80%). Baseline clinical characteristics between the two treatment groups were comparable i.e., age (P>0.896), gender (P>0.999), coma at presentation (P>0.999), immunosuppression (P>0.623), number of abscesses (P>0.999) and interval between presentation and surgery (P>0.447). Overall mortality was 40%. The overall outcome was significantly better (P<0.001) in patients treated with antifungal therapy before surgery. All 11 patients who received antifungal therapy before surgery survived, but only preoperative itraconazole treatment was statistically associated with an improved survival compared to delayed treatment. CONCLUSION: Cerebral aspergillosis was largely a disease of immune competent people (80%). Overall mortality was 40%. The outcome was significantly better in patients treated with antifungal therapy (especially itraconazole) before surgery suggesting a possible beneficial effect of pre-surgical treatment with antifungal therapy.