Cerebral Venous Thrombosis at High Altitude: Analysis of 28 Cases.

OBJECTIVE: An association between cerebral venous sinus thrombosis (CVST) and high altitude has been previously proposed, but limited published data exist to support this association. We investigated 28 cases of CVST occurring at high altitude and sought to describe patient demographics, altitude and acclimatization, hematological laboratory findings, neuroimaging, treatment, and prognosis in these cases. METHODS: Twenty-eight cases of symptomatic CVST occurring at high altitude were identified between the months of August 2017 and December 2018, in collaboration with Military Hospital, Rawalpindi and Combined Military Hospital, Skardu (Pakistan). Follow-up visits were performed at 1 and 6 months. RESULTS: Twenty-seven (96%) of the patients were males, and the mean age was 33 years. In total, 32.1% were smokers. The mean NIHSS score on presentation was 5.5. 85.7% of the cases occurred at altitude higher than 8,000 feet. On average 107.8 days were spent at a high altitude prior to CVST. Totally, 71.4% had acclimatized for >2 weeks. The mean hemoglobin (Hb) value was 16.7 g/dL and 50% had d-dimer levels higher than 1,000 ng/mL. On MRI, 25% showed signs of hemorrhage and 14.3% showed infarcts. Treatments provided include low-molecular-weight heparin and Rivaroxaban and were associated with good outcomes. CONCLUSION: CVST is not uncommon at high altitude (>8,000 feet). It is predominantly a male disease. Most patients have high Hb and high D-dimer levels. The overall outcome was good.

Association between migraine and Body Mass Index in patients reporting at a military hospital, Rawalpindi.

The objective of this study was to determine the association between Body Mass Index (BMI) and migraine. This prospective study took place from 5th February, 2017 to 5th August, 2017 at a Military Hospital in Rawalpindi. Migraine in subjects was diagnosed according to the ICHD-III criteria by clinicians after taking an informed, written consent from 78 patients and the data was analysed using SPSS 22. Of the 78 patients, 35(44.9%) were males and 43(55.1%) were females. Out of the 78 subjects, 9(11.5%) were underweight, 33(41.0%) were of normal weight, 9(14.10%) were overweight, 19(24.4%) were obese and 7(9.0%) were morbidly obese. The p-value calculated was 0.892 which indicates no significant evidence of any association between BMI and migraine in the survey population reporting at the Rawalpindi Military Hospital. A follow-up study at a national level with much larger sample size will be able to better predict the changing results in our country, because as of now the association between BMI and migraine is debatable.

Stroke at Moderate and High Altitude.

Syed, Maryam J., Ismail A. Khatri, Wasim Alamgir, and Mohammad Wasay. Stroke at moderate and high altitude. High Alt Med Biol. 23:1-7, 2022. Background: Stroke at high altitude is an understudied area in stroke research. With improvements in road infrastructure, access to high-altitude areas for recreation and living purposes has risen. Subsequently, it has been anticipated that due to normal physiological changes to high altitude the incidence of stroke is also likely to increase in these regions. Methods: We searched PubMed for available literature about stroke at high altitude. Cross-referencing was done from available articles and through other scientific search engines. Relevant case series and case reports were included in this review of the topic. Results: Only one review article, eight case series (including review of literature), and seven case reports were identified that could be included in this review. Most of the available data come from moderate and high altitude. Conclusions: There is limited available literature about stroke at high and extreme altitudes. Stroke at high altitude is likely to become an important subset of stroke population. Currently, there is inadequate knowledge about the incidence and prevalence, mechanisms, and stroke outcomes. Cerebral venous thrombosis is more common than arterial stroke. Stroke is probably secondary to conventional risk factors, polycythemia, and other coagulopathies. A case-control study may identify the at-risk population for stroke at moderate and high altitudes.

Corrigendum: The NMT Scalp EEG Dataset: An Open-Source Annotated Dataset of Healthy and Pathological EEG Recordings for Predictive Modeling.

[This corrects the article DOI: 10.3389/fnins.2021.755817.].

Hyperglycemia Presenting with Hemichorea-Hemiballismus and T-1 Hyperintensity on MRI Brain.

Hemichorea-hemiballismus, secondary to hyperglycemia, is a rare but easily treatable condition that is usually associated with type II diabetes mellitus. This is a case of a 68- year lady, with long-standing, poorly controlled diabetes mellitus, who presented with disabling right-sided hemichorea-hemiballismus. The T1-weighted magnetic resonance imaging revealed hyperintensity in the basal ganglia. The abnormal movements subsided within a few days after achieving euglycaemia with insulin therapy. This case highlights the importance of treatment of hyperglycaemia in a diabetic patient presenting with acute or sub-acute abnormal movement disorder. Key Words: Hemichorea, Hemiballismus, Hyperglycemia, T-1 hyperintensity.

The NMT Scalp EEG Dataset: An Open-Source Annotated Dataset of Healthy and Pathological EEG Recordings for Predictive Modeling.

Electroencephalogram (EEG) is widely used for the diagnosis of neurological conditions like epilepsy, neurodegenerative illnesses and sleep related disorders. Proper interpretation of EEG recordings requires the expertise of trained neurologists, a resource which is scarce in the developing world. Neurologists spend a significant portion of their time sifting through EEG recordings looking for abnormalities. Most recordings turn out to be completely normal, owing to the low yield of EEG tests. To minimize such wastage of time and effort, automatic algorithms could be used to provide pre-diagnostic screening to separate normal from abnormal EEG. Data driven machine learning offers a way forward however, design and verification of modern machine learning algorithms require properly curated labeled datasets. To avoid bias, deep learning based methods must be trained on large datasets from diverse sources. This work presents a new open-source dataset, named the NMT Scalp EEG Dataset, consisting of 2,417 recordings from unique participants spanning almost 625 h. Each recording is labeled as normal or abnormal by a team of qualified neurologists. Demographic information such as gender and age of the patient are also included. Our dataset focuses on the South Asian population. Several existing state-of-the-art deep learning architectures developed for pre-diagnostic screening of EEG are implemented and evaluated on the NMT, and referenced against baseline performance on the well-known Temple University Hospital EEG Abnormal Corpus. Generalization of deep learning based architectures across the NMT and the reference datasets is also investigated. The NMT dataset is being released to increase the diversity of EEG datasets and to overcome the scarcity of accurately annotated publicly available datasets for EEG research.

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.

Clearing the Fog: Is Hydroxychloroquine Effective in Reducing Coronavirus Disease-2019 Progression? A Randomized Controlled Trial.

Background Hydroxychloroquine (HCQ) has been considered for the treatment of coronavirus disease 2019 (COVID-19), but data on its efficacy are conflicting. We analyzed the efficacy of HCQ along with standard of care (SOC) treatment, compared with SOC alone, in reducing disease progression in mild COVID-19. Methods A single-center open-label randomized controlled trial was conducted from April 10 to May 31, 2020 at Pak Emirates Military Hospital, Rawalpindi. Five hundred patients of both genders between the ages of 18 and 80 years with mild COVID-19 were enrolled in the study. A total of 349 patients were assigned to the intervention group (standard dose of HCQ plus SOC) and 151 patients were assigned to SOC only. The primary outcome was progression of disease while secondary outcome was polymerase chain reaction (PCR) negativity on days 7 and 14. The results were analyzed on Statistical Package for Social Sciences (SPSS; IBM Corp., Armonk, NY) version 23. A p-value <0.05 was considered significant.  Results The median age of the intervention group was 34 ± 11.778 years and control group was 34 ± 9.813 years. Disease progressed in 16 patients, 11 (3.15%) of which were in the intervention group and 5 (3.3%) in the control group (p-value = 0.940). PCR negative cases in intervention and control groups on day 7 were 182 (52.1%) and 54 (35.8%), respectively (p-value = 0.001); and on day 14 were 244 (69.9%) and 110 (72.9%), respectively (p-value = 0.508). Consecutive PCR negativity on days 7 and 14 was observed in 240 (68.8%) patients in the intervention group compared to 106 (70.2%) in the control group (p-value = 0.321). Conclusion The addition of HCQ to SOC in hospitalized mild COVID-19 patients neither stops disease progression nor helps in early and sustained viral clearance.

Haematological Parameters And Outcome In Hospitalized Patients With Covid-19: A Developing Country Experience.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a multisystem disorder and haematological abnormalities are frequently documented in affected patients. METHODS: This retrospective study included 549 patients hospitalized with COVID-19 from 1st June to 15th July 2020 at Pak Emirates hospital, Rawalpindi Pakistan. p<0.05 was considered statistically significant. RESULTS: Median age was 60 years (range 12-94 years), males 442 (80.5%) and females 107 (19.5%). There was no patient with mild illness, 181 (32.9%) had moderate, 158 (28.7%) severe and 210 (38.2%) patients had critical disease. Patients with severe and critical disease had lower absolute lymphocyte count (ALC) and platelets (p<0.001 for both) while higher white blood cell count (WBC), neutrophil lymphocyte ratio (NLR), C-reactive protein (CRP), interleukin-6 (IL-6) and lactate dehydrogenase levels (LDH) levels (all p<0.001). Overall survival of study cohort was 83.2% (n=457). Median haemoglobin and platelet count were significantly lower (p<0.001) while WBC, ANC, NLR, prothrombin time (PT), activated partial thromboplastin time (APTT), ferritin, IL-6, LDH were significantly higher (p<0.001) for patients who died. On multivariate logistic regression analysis WBC count>10x109/l (odds ratio [OR] 2.19 [95% CI 1.3-4.2] p=0.01), NLR>9 (OR 3.4 [95% CI 0.87-6.8], p<0.001), platelets<150x109/l (OR 3.9 [95% CI 1.4-9.8] p<0.001), CRP >100; (OR 4.1[95% CI 0.78-10.9] p<0.001) and ferritin >1000 (OR 5.3 [95% CI 1.9- 13.5], p<0.001) were associated with increased risk of death in patients with COVID-19. CONCLUSION: Monitoring of haematological, coagulation and inflammatory parameters provide reliable, convenient, rapid and cost-effective method for predicting disease severity, complications and prognosis of COVID-19 patients.

Therapeutic plasma exchange for coronavirus disease-2019 triggered cytokine release syndrome; a retrospective propensity matched control study.

BACKGROUND: Cytokine release syndrome (CRS) plays a pivotal role in the pathophysiology and progression of Coronavirus disease-2019 (COVID-19). Therapeutic plasma exchange (TPE) by removing the pathogenic cytokines is hypothesized to dampen CRS. OBJECTIVE: To evaluate the outcomes of the patients with COVID-19 having CRS being treated with TPE compared to controls on the standard of care. METHODOLOGY: Retrospective propensity score-matched analysis in a single centre from 1st April to 31st July 2020. We retrospectively analyzed data of 280 hospitalized patients developing CRS initially. PSM was used to minimize bias from non-randomized treatment assignment. Using PSM 1:1, 90 patients were selected and assigned to 2 equal groups. Forced matching was done for disease severity, routine standard care and advanced supportive care. Many other Co-variates were matched. Primary outcome was 28 days overall survival. Secondary outcomes were duration of hospitalization, CRS resolution time and timing of viral clearance on Polymerase chain reaction testing. RESULTS: After PS-matching, the selected cohort had a median age of 60 years (range 32-73 in TPE, 37-75 in controls), p = 0.325 and all were males. Median symptoms duration was 7 days (range 3-22 days' TPE and 3-20 days controls), p = 0.266. Disease severity in both groups was 6 (6.6%) moderate, 40 (44.4%) severe and 44 (49%) critical. Overall, 28-day survival was significantly superior in the TPE group (91.1%), 95% CI 78.33-97.76; as compared to PS-matched controls (61.5%), 95% CI 51.29-78.76 (log rank 0.002), p<0.001. Median duration of hospitalization was significantly reduced in the TPE treated group (10 days vs 15 days) (p< 0.01). CRS resolution time was also significantly reduced in the TPE group (6 days vs. 12 days) (p< 0.001). In 71 patients who underwent TPE, the mortality was 0 (n = 43) if TPE was done within the first 12 days of illness while it was 17.9% (deaths 5, n = 28 who received it after 12th day (p = 0.0045). CONCLUSION: An earlier use of TPE was associated with improved overall survival, early CRS resolution and time to discharge compared to SOC for COVID-19 triggered CRS in this selected cohort of PS-matched male patients from one major hospital in Pakistan.

CALL Score and RAS Score as Predictive Models for Coronavirus Disease 2019.

BACKGROUND:  Coronavirus disease 2019 (COVID-19) is a novel infectious disease of multi-system involvement with significant pulmonary manifestations. So far, many prognostic models have been introduced to guide treatment and resource management. However, data on the impact of measurable respiratory parameters associated with the disease are scarce. OBJECTIVE:  To demonstrate the role of Comorbidity-Age-Lymphocyte count-Lactate dehydrogenase (CALL) score and to introduce Respiratory Assessment Scoring (RAS) model in predicting disease progression and mortality in COVID-19. METHODOLOGY:  Data of 252 confirmed COVID-19 patients were collected at Pak Emirates Military Hospital (PEMH) from 10th April 2020 to 31st August 2020. The CALL score and proposed factors of RAS model, namely respiratory rate, oxygen saturation at rest, alveolar arterial gradient and minimal exercise desaturation test, were calculated on the day of admission. Progression of disease was defined and correlated with measured variables. Univariate and multivariate Cox regression analysis for each variable, its hazard ratio (HR) and 95% confidence interval (CI) were calculated, and a nomogram was made using the high-risk respiratory parameters to establish the RAS model. RESULTS:  Progression of disease and death was observed in 124 (49.2%) and 49 (19.4%) patients, respectively. Presence of more than 50% of chest infiltrates was significantly associated with worsening disease and death (p-value <0.001). Death was observed in 100% of patients who had critical disease category on presentation. Regression analysis showed that the presence of comorbidity (n: 180), in contrast to other variables of CALL score, was not a good prognosticator of disease severity (p-value: 0.565). Nonetheless, the CALL model itself was validated to be a reliable prognostic indicator of disease progression and mortality. Some 10 feet oxygen desaturation test (HR: 0.99, 95%CI: 0.95-1.04, p--value: 0.706) was not a powerful predictor of the progression of disease. However, respiratory rate of more than 30 breaths/minute (b/m) (HR: 3.03, 95%CI: 1.77-5.19), resting oxygen saturation of less than 90% (HR: 2.41, 95%CI: 1.15-5.06), and an elevated alveolar-arterial oxygen gradient (HR: 2.14, 95%CI: 1.04-4.39) were considered statistically significant high-risk predictors of disease progression and death, in the formed RAS model. The model resulted in 85% (95%CI: 80%-89%) of area under the receiver operating characteristic curve (AUROC), with substantial positive (76%, 95%CI: 68%-83%) and negative predictive values (80%, 95%CI: 73%-87%) for a cutoff value of seven. Patients with higher CALL and RAS scores also resulted in higher mortality. CONCLUSION:  CALL and RAS scores were strongly associated with progression and mortality in patients with COVID-19.

Comparison of clinical causes of death with autopsy diagnosis using discrepency classification.

OBJECTIVE: To determine the usefulness of autopsy findings in the quality improvement of patients care. DESIGN: An observational study. PLACE AND DURATION OF STUDY: Departments of Pathology and Medicine, Combined Military Hospital (CMH) Kharian, a tertiary care hospital, from January 2001 to December 2003. MATERIALS AND METHODS: The clinical and necropsy findings of all the cases, who died in hospital and had undergone autopsy examination at CMH, Kharian, from January 2001 to December 2003, were retrieved from record of clinical case sheet data and autopsy record of the hospital. The two were analyzed and compared according to the discrepancy classification. The exclusion and inclusion criteria, the international classification of disease (ICD) to code deaths, the global burden of disease (GBD) system to classify and group diseases, and the Goldman discrepancy classification to compare clinical and autopsy diagnosis and classify the discrepancies, were used as described. RESULTS: The death rate varied from 0.94% to 1.29% and autopsy rate from 4.69% to 10.10% annually between January 2001 and December 2003. The number of cases classified according to GBD system was 3 (5%) in Group 1, 26 (43.33 %) in Group 2 and 31 (51.66 %) in Group 3. The discrepancy classes included 9 (15 %) class I major discrepancies and 3 (5 %) class II major discrepancies. Non-discrepant diagnosis was seen in 37 cases (61.66 %) and 11 cases (18.32 %) were non-classifiable. CONCLUSION: This study showed the usefulness of autopsy findings in the quality improvement of the diagnosis and management of the disease by showing only a minority of cases with discrepant diagnosis of the cause of death.