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Background: Environmental enteric dysfunction (EED), a chronic inflammatory condition of the small intestine, is an important driver of childhood malnutrition globally. Quantifying intestinal morphology in EED allows for exploration of its association with functional and disease outcomes., Objectives: We sought to define morphometric characteristics of childhood EED and determine whether morphology features were associated with disease pathophysiology., Methods: Morphometric measurements and histology were assessed on duodenal biopsy slides for this cross-sectional study from children with EED in Bangladesh, Pakistan, and Zambia (n = 69), and those with no pathologic abnormality (NPA; n = 8) or celiac disease (n = 18) in North America. Immunohistochemistry was also conducted on 46, 8, and 18 biopsy slides, respectively. Linear mixed-effects regression models were used to reveal morphometric differences between EED compared with NPA or celiac disease and identify associations between morphometry and histology or immunohistochemistry among children with EED., Results: In duodenal biopsies, median EED villus height (248 μm), crypt depth (299 μm), and villus:crypt (V:C) ratio (0.9) values ranged between those of NPA (396 μm villus height; 246 μm crypt depth; 1.6 V:C ratio) and celiac disease (208 μm villus height; 365 μm crypt depth; 0.5 V:C ratio). Among EED biopsy slides, morphometric assessments were not associated with histologic parameters or immunohistochemical markers, other than pathologist-determined subjective semiquantitative villus architecture., Conclusions: Morphometric analysis of duodenal biopsy slides across geographies identified morphologic features of EED, specifically short villi, elongated crypts, and a smaller V:C ratio relative to NPA slides, although not as severe as in celiac slides. Morphometry did not explain other EED features, suggesting that EED histopathologic processes may be operating independently of morphology. Although acknowledging the challenges with obtaining relevant tissue, these data form the basis for further assessments of the role of morphometry in EED., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Balo's concentric sclerosis (BCS) is a rare subtype of multiple sclerosis. Advanced MRI metrics, such as magnetization transfer ratio (MTR), fractional anisotropy (FA), mean diffusivity (MD), and the ratio of total N-acetylaspartate concentration/total creatine concentration (tNAA/tCr) using proton magnetic resonance spectroscopy ( 1 H-MRS), are commonly used in research studies to investigate the effect of a disease modifying therapy (DMT). We report a patient diagnosed with BCS, receiving ocrelizumab, and provide a comparison of the lesion volume, T1-gadolinium lesion volume, MTR, FA, MD, and MRS metrics at baseline, 6- and 12-month follow-up. There was a reduction in Balo's lesion volume on fluid-attenuated inversion recovery (FLAIR) imaging observed in our patient from baseline (23.925 mL) to 12-month follow-up (2.391 mL), with the largest decrease from baseline to 6-month follow-up (3.650 mL). There was no T1-gadolinium enhancement seen at month 6 and 12. The MTR of the lesion did not change significantly (baseline = 50.9%, 6-month = 49.9%, 12-month =50.1%) but the FA increased from 0.188 (at baseline) to 0.304 (at 6 months), while the 12-month follow-up FA was 0.297. We also noted a reduction in MD from baseline (1.333 × 10 -3 mm 2 /s) to 6-month follow-up (1.037 × 10 -3 mm 2 /s), while the 12-month follow-up MD was 1.086 × 10 -3 mm 2 /s. There was a 10.3% increase in tNAA/tCr from 1.583 (at month 0) to 1.747 (at month 12). Our results demonstrate for the first time a direct effect of ocrelizumab on BCS lesions. To validate our findings, more observations are needed in a larger group of BCS patients., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Over the past few decades, the global healthcare community has achieved remarkable success in controlling many communicable diseases across various regions. However, non-communicable diseases now constitute a significant portion of disease morbidity and mortality, particularly in low- and middle-income countries (LMICs). Among these, cancer, in particular, is witnessing a notable increase in incidence in many LMICs. Among cancers, neurological tumours bear significant impact in terms of long-term disability, escalating costs of comprehensive multidisciplinary care, and often encounter resource-related and systemic delays in care leading to worse outcomes. This opinion paper discusses key concepts in developing global neuro-oncology care, with specific case examples from Pakistan to illustrate methods for improving care in these underserved regions. Additionally, it outlines strategic approaches and potential solutions to address these challenges, aiming to provide a roadmap for enhancing neuro-oncology care in LMICs.

Objective: To evaluate choroid plexus (CP) volume as a biomarker for predicting clinical disability and retinal layer atrophy in relapsing remitting multiple sclerosis (RRMS)., Methods: Ninety-five RRMS patients and 26 healthy controls (HCs) underwent 3 T whole brain MRI, expanded disability status scale (EDSS) and optical coherence tomography (OCT). Fully automated intra-retinal segmentation was performed to obtain the volumes of the retinal nerve fiber layer (RNFL), combined ganglion cell layer -inner plexiform layer (GCIPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), retinal pigment epithelium (RPE), total macular volume (TMV) and papillomacular bundle (PMB). Automated segmentation of the CP within the lateral ventricles was performed and the choroid plexus volume (CPV) was normalized by total intracranial volume (TIV). Linear regression analysis and generalized estimating equation (GEE) models were applied to evaluate relationships between nCPV and EDSS, T2 lesion volume, disease duration, and retinal layer volumes, followed by Bonferroni correction analysis for multiple comparisons., Results: RRMS patients had larger tChPV compared to HCs (p < 0.001). After Bonferroni correction, there was a significant positive correlation between tChPV and EDSS (r 2  = 0.25, p = 0.0002), disease duration (r 2  = 0.30, p = 0.01), and T2 lesion volume (r 2  = 0.39, p = 0.0000). A robust negative correlation was found between tChPV and RNFL (p < 0.001), GCIPL (p = 0.003), TMV (p = 0.0185), PMB (p < 0.0001), G (p = 0.04), T(p = 0.0001)., Conclusions: Our findings support the association of tChPV with disability and altered retinal integrity in RRMS., Competing Interests: Declaration of competing interest The authors declared no conflict of interest relevant to this manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Multiple sclerosis (MS) is a chronic, autoimmune, demyelinating disease of the central nervous system (CNS). Microbes, including bacteria and certain viruses, particularly Epstein-Barr virus (EBV), have been linked to the pathogenesis of MS. While there is currently no cure for MS, antibiotics and antivirals have been studied as potential treatment options due to their immunomodulatory ability that results in the regulation of the immune process. The current issue addressed in this systematic review is the effect of antimicrobials, including antibiotics, antivirals, and antiparasitic agents in animals and humans. We performed a comprehensive search of PubMed, Google Scholar, and Scopus for articles on antimicrobials in experimental autoimmune encephalomyelitis animal models of MS, as well as in people with MS (pwMS). In animal models, antibiotics tested included beta-lactams, minocycline, rapamycin, macrolides, and doxycycline. Antivirals included acyclovir, valacyclovir, and ganciclovir. Hydroxychloroquine was the only antiparasitic that was tested. In pwMS, we identified a total of 24 studies, 17 of them relevant to antibiotics, 6 to antivirals, and 1 relevant to antiparasitic hydroxychloroquine. While the effect of antimicrobials in animal models was promising, only minocycline and hydroxychloroquine improved outcome measures in pwMS. No favorable effect of the antivirals in humans has been observed yet. The number and size of clinical trials testing antimicrobials have been limited. Large, multicenter, well-designed studies are needed to further evaluate the effect of antimicrobials in MS.

Objective: To quantify the frequency of craniopharyngiomas presenting to tertiary care neurosurgical centres, the demographics and mortality rate, and commonly presenting to neurosurgical practice., Method: Our study was a retrospective cross-sectional analysis of patients admitted at 32 neurosurgical centres between January 1, 2019, and December 31, 2019, with brain tumour. Kruskal Wallis analysis was used to determine normality; normally distributed variables were reported as means with standard deviation, while median with interquartile range was used for non-normally distributed variables., Results: Of 2750 patients with brain tumours, 114 patients presented with craniopharyngioma. The median age at diagnosis was 18 years, with 42 (42.8%) patients below the age of 15, 40 (40.9%) patients aged 15-39, and 16 (16.3%) patients aged 40 and above. There were 70 (61.4%) males and 44 (38.6%) females in our cohort. Gross total resection was performed in 42(36.8%), 45 (39.5%) underwent subtotal resection, 9 (7.9%) underwent CSF diversion only, and 2 (1.8%) had a biopsy. Most of our patients 94(82.5%) presented to public hospitals, with 20 (17.5%) patients presenting to private hospitals (p=0.002). The overall survival at two years was 86.8% in patients with known outcomes, and only 10% of patients died within 30 days of surgery., Conclusions: Craniopharyngiomas comprised a small portion of all brain tumours in our region. They are more common in males and in patients from the lower socioeconomic class. These patients mainly presented to public sector hospitals, and the three highest volume centres were all public sector institutions. The overall survival rate at two years in our region is lower than in other regions.

Objective: To identify the surgical incidence and prevalence of schwannoma in our region and quantify the demographic, surgical, neoplastic, and outcome characteristics of the patients diagnosed with schwannoma.., Methods: A retrospective cross-sectional study was conducted from January 1 to December 31, 2019. Enrolled were 32 of the highest volume neurosurgical centres in Pakistan. Patients with a histopathological diagnosis of schwannoma and radiological imaging were included in the study. Medical records were reviewed for data, and SPSS version 25 was used for statistical analysis. Patients were followed up for one year, which was the duration of the study., Results: From 2750 patients diagnosed with brain tumours, 148 patients had schwannomas. Out of these, 84 (56.8%) patients were male, and 64 (43.2%) patients were female. The mean age of the patients was 39 ± 14 years. The socioeconomic statuses of the enrolled patients were lower in 72 (53.3%) patients, middle in 57 (42.2%) patients, and upper middle to upper in 6 (4.4%) patients. All patients underwent surgery, 14 patients received radiotherapy, and two patients received chemotherapy. In our cohort, 115 (77.7%) patients presented to public sector hospitals, with only 33 (22.3%) patients presenting to private hospitals. At the end of the study period, 60 (40.5%) patients had been lost to follow-up. Of the remaining 88 patients, 75 (85.2%) were alive. The mortality rate on a one-year follow-up was 14.8%., Conclusions: Schwannoma comprises a larger percentage of the brain tumours in our regions than reported in the literature. The high mortality rate is of particular concern and warrants further investigation to improve patient care and outcomes.

Objective: To define the landscape of treatment patterns and current epidemiological data regarding gliomas in Pakistan., Methods: As part of the Pakistan Brain Tumour Epidemiology Study (PBTES), data were collected from 32 neurosurgical centres across the country. Our retrospective study looked at patients who underwent surgical procedures for gliomas in 2019 in neurosurgical centres. The data was collated and analysed using STATA version 15., Results: A total of 781 patients with gliomas were identified 479(61.8%) in public sector hospitals, 302(39.1%) in the private sector). The most common histopathological subtypes were glioblastoma 262 (33.5%), followed by astrocytoma 147(18.8%) and oligodendroglioma 93(11.9%). Gender distribution was skewed towards men 508(65%). Private institution hospitals performed surgical biopsies as the first surgical procedure 75(23%) more often than public hospitals 38(9%). Chemotherapy was given to 115(29.8%) patients, and there was no data regarding 467(53%) of patients. Similarly, only 202(43.9%) patients received radiation therapy, and there was no data for 469(60%) of patients. For high-grade gliomas specifically, only 95(31.8%) patients with HGG have a record of receiving radiation therapy, and only 57(18.9%) had a record of being started on chemotherapy., Conclusion: Our study highlighted gaps in glioma management within Pakistan, with only around half of our patients receiving chemotherapy and radiotherapy, despite it being indicated. In our experience, high-grade tumours were diagnosed at a younger age than in high-income countries, but overall, glioblastoma was a smaller constituent of our tumour sample than expected.

Background: Due to the differences in size and invasiveness when compared to non-giant macroadenomas (nGPAs), giant pituitary adenomas (GPAs) are considerably harder to resect. This study aimed to differentiate GPAs from nGPAs, based on the presenting complaints, surgical approaches, peri- and postoperative outcomes., Methods: We retrospectively analyzed cases of pituitary macroadenomas that underwent surgical resection at a tertiary care hospital. GPAs were tumors greater than 4 cm in the largest dimension, while nGPAs were tumors smaller than 4 cm. 55 GPA patients and 70 nGPA patients from 2006 to 2017 were included. Demographic, perioperative, and post-operative outcomes were evaluated. Group comparisons for continuous variables were made using an independent t-test/Mann Whitney U test and categorical data was analyzed on Chi-square/Fisher exact test; a p-value of < 0.05 was considered significant., Results: Visual deterioration was the most common complaint, reported by 61.4% of nGPA patients and 81.8% of GPA patients. The mean extent of gross total resection was 47.1% in nGPA patients and 18.2% in GPA patients (p = 0.001). After surgery, tumor recurrence was seen in 1.4% of nGPA patients and 18.2% of GPA patients (p = 0.001). First re-do surgery was required in 5.7% of nGPA patients and 25.5% of GPA patients (p = 0.004)., Conclusion: Compared to nGPAs, GPAs are more likely to present with a higher number of preoperative symptoms, and lesser chances of gross total tumor resection. GPAs are also associated with a higher rate of recurrence, which results in more follow-up procedures. Larger, multi-center longitudinal studies need to be done to validate these findings., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To examine the effect of distance travelled for brain tumour surgery on patient outcomes in an LMIC., Methods: Data were collected as part of the Pakistan Brain Tumour Epidemiology Study (PBTES) for brain tumour patients who underwent surgery in 2019. Mapping software was used to calculate the distance travelled by each patient from their primary address to the hospital. This was analysed in correlation with outcomes (change in KPS score, current status) and demographic variables., Results: Of 2366 patients, the median distance travelled across the country was 104 km (IQR: 9.07 - 304). Only 970 (41%) patients had access to brain tumour surgical care within 50 km of their primary address. A total of 372 (15.7%) patients requiring brain tumour surgery had to travel more than 500 km to reach their primary care hospital. Patients travelling more than 50 km for brain tumour surgery had better pre- and post-surgery Karnofsky performance scores (p<0.001) than those travelling less than 50 km. The overall survival for these patients was also better (82.4% vs 75.7%, p= 0.002) compared to patients travelling less than 50 km., Conclusions: The distance to a hospital dictates a patient's access to continuity of care through adjuvant chemoradiotherapy and regular follow-ups. Less than half of brain tumour patients in Pakistan had access to brain tumour surgery care within 50 km of their homes. Overall outcomes were significantly better in patients travelling more than 50km for neurosurgical care - suggesting a distance bias effect.

Objectives: To provide information about brain tumour epidemiology in Pakistan and potential associated risk factors due to family, medical and social characteristics., Methods: A retrospective cross-sectional nationwide study was designed by the Pakistan Society of Neuro-oncology, to include patients diagnosed with brain tumours in Pakistan retrospectively, from January 1, 2019- December 31, 2019. The study intended to involve data from all age groups for all brain tumour cases, irrespective of histopathology which would determine the national prevalence and incidence of these tumours., Results: A total of 2750 brain tumour cases were recorded, of which 1897 (69%) were diagnosed in the public sector. MRIs were a more common radiological study compared to CT scans. Gliomas were the most common tumours 778 (28.29%), while pineal tumours were the least common 19 (0.69%). The median age at diagnosis for males was 36 (24-49), while the median age at diagnosis for females was 37 (24-48). Hypertension was the most common co-morbidity in patients diagnosed with a brain tumour, 524 (51.89%), and smoking was the most frequent social behaviour, 355 (62.02%). Findings indicate a low metastasis frequency and few females seeking care., Conclusions: The PBTES and the PBTC have presented an opportunity and platform for hospitals and health professionals to work together to strengthen cancer care health systems, ensure implementation of treatment guidelines and conduct regular cancer registration.

Objective: To quantify the metastatic brain tumour burden presenting to tertiary care neurosurgical centres, the demographics and mortality rate, and the type of metastatic tumours commonly presenting to neurosurgical practice., Method: A cross-section retrospective study was conducted on patients diagnosed with brain tumours from 32 neurosurgical centres across Pakistan between January 1, 2019, to December 31, 2019. At least one neurosurgical resident and one neurosurgical faculty member were recruited from each centre as members of the Pakistan Brain tumour consortium. Mean with standard deviation or median with interquartile range was reported as variables., Results: Of 2750 patients in this cohort, 77 (2.8%) were diagnosed with metastatic brain tumours. The median age of these patients was 52 (IQR= 43-60) years; 9 (14%) adults were aged 20-39 years, 37 (57%) were aged 40-59, and 19 (29%) were aged 60 and above. There were 62 (82.7%) married patients with 4% unmarried. The median KPS score both pre and post-surgery was 80 (IQR= 60-90, 70-90 respectively), and 43 (55.8%) patients were lost to follow-up. The mortality rate for patients that followed up was 50%, 17 patients were alive, and 17 were deceased at the end of the study period. The 30-day mortality rate amongst our patients was 11.8% (n=4)., Conclusions: The number of patients presenting to neurosurgical care with brain metastases is much lower than the expected incidence of metastatic brain lesions. Multidisciplinary integration and the establishment of a registry to track patients diagnosed with brain tumours is the first step in ensuring better care for these patients.

Objective: To observe the patient characteristics and centres providing neuro-oncological care in public and private health hospitals in Pakistan., Method: The Pakistan Association of Neuro-oncology carried out a retrospective, cross-sectional study in 2019 on patients admitted to 32 hospitals in Pakistan, with dedicated neurosurgical facilities. Patients with a histopathological diagnosis of an intracranial tumour were included., Results: Public health care facilities catered for 84% patients with ages between 20 and 60 years and children having intracranial tumours. Private centres were utilised by 66.7% patients from the upper socioeconomic sector. More patients were lost to follow-up in the public sector (n = 784) versus in the private sector (n = 356). Mortality was also higher in the public sector hospitals, (13.9%) as compared to 9.6% in the private sector., Conclusions: Public and private sector health services for neuro-oncological care in Pakistan still have a long way to go to cover the gaps for unmet needs. Strengthening health systems for brain tumour care is imperative to increase both the access to care and the quality of care to fulfil this need.

Objective: To investigate waiting times for brain tumour surgery in Pakistan from a nationwide sample and highlight specific affected patient populations., Method: A nationwide study was conducted as part of the Pakistan Brain Tumour Epidemiology Study; data from 32 high-volume neurosurgical centres were collected. The national sample included 2,750 patients. Time to surgery was calculated by the difference in dates recorded for radiological diagnosis and the date of the first surgery. This was further stratified according to demographic factors, histopathological diagnosis, type of surgical procedure performed and survival outcomes., Results: The data of 1,474 patients for time to surgery was available. Patients travelling to public hospitals had significantly longer mean wait times (94.07 (CI: 85.29, 102.84) vs 75.14 (CI: 54.72, 95.56) days, p<0.001). Significant differences were seen between patients of various age groups, as adolescents (116.63 (CI: 65.27, 167.98) days) and young adults (103.34 (CI: 85.96, 120.72) days) had higher waiting times compared to middle-aged (72.44 (CI: 61.26, 83.61) days) and older (48.58 (CI: 31.17, 65.98) days) adults. No difference was seen between the genders. A significantly longer time to surgery was observed for middle- and lower-socioeconomic class patients. Those undergoing gross total resection of the tumour had significantly (p<0.001) longer waiting times for surgery when compared to STR (sub-total resection), biopsy, and CSF-diversion procedures, for all tumour types. Patients diagnosed with meningioma had the most prolonged waiting periods (106 (CI: 76, 95) days). Gliomas had a mean waiting period of 88 (CI: 73, 103) days across the country. Low-grade gliomas had significantly (p=0.031) longer mean waiting times (99.73 (CI: 61.91, 127.36) days) in comparison to high-grade gliomas (70.13 (CI: 43.39, 89.69 ) days). A significant difference was seen between waiting times for patients who survived surgical procedures for a brain tumour on the most recent follow-up and those who had expired (91.87 (CI: 79, 107.74) vs 77.41 (CI: 59.90, 94.91) days, p<0.001)., Conclusions: Prolonged delays to surgery are a significant barrier within low-and-middle-income countries, leading to adverse outcomes for patients. Patients undergoing brain tumour surgery at public hospitals from lower or middle SES and electing for gross resections were more likely to have longer delays.

Objective: To build a comprehensive brain tumour database that will allow us to analyse in detail the prevalence, demographics, and outcomes of the disease in paediatric, adolescent, and young adult age groups., Method: A national cross-sectional study was conducted at 32 centres, and data regarding patient demographics and brain tumours were collected. This data was then stratified based on age groups, healthcare sectors, socioeconomic status, tumour types, and surgical outcomes., Results: Most of the patients who were diagnosed with brain tumours belonged to a lower socioeconomic background and went to public sector hospitals. More males were diagnosed with and treated for brain tumours in the paediatric, adolescent, and young adult populations. The most common tumour in the paediatric population was medulloblastoma (23.7%) and the most common tumour in the adolescent (27.8%) and young adult population (34.7%) was glioma. Significant improvement in KPS scores were seen for: craniopharyngioma (p = 0.001), meningioma (p < 0.0005) and pituitary adenoma (p < 0.0005)., Conclusions: This study shows that in all three age groups, there was a greater prevalence in males. Most of the patients belonged to a lower-middle-income class background and most patients presented to public sector hospitals. Greater knowledge of these parameters unique to each age group is the key to understanding and alleviating the burden of disease. Cancer registries, specifically brain tumour registries that keep up-to-date records of these patients, are essential to identify and keep track of these unique parameters to advance medical research and treatment strategies, ultimately lowering the disease burden.

Objective: To identify symptoms and risk factors and promptly diagnose, treat, and manage pituitary adenomas. Prioritizing care for pituitary adenomas will reduce the prolonged disability., Method: Patients with a histopathological diagnosis of a pituitary adenoma that presented at 32 tertiary care neurosurgical centres were included. The information recorded included demographics, treatment methods, adjuvant chemoradiotherapy and loss to follow-up. Data on tumour size, functionality, and laterality were collected., Results: Of the 32 hospitals surveyed, 24 operated on pituitary adenomas, and treated 277 patients. The mean age at diagnosis was 39.8 ± 13 years, with a majority of males (63.5%) being diagnosed than females. Paediatric cases constituted only 4.7% of the total pituitary adenomas operated upon. Gross total resection was reported for 155 (56%) of all pituitary adenoma patients. Majority of the patients affected by pituitary adenomas (80.1%) were from the working class., Conclusions: Highlighting care for non-malignant brain tumours is important for Pakistan's health system. Evidence pertaining to gender and age disparities indicates that males in the younger age groups are predominantly affected, which takes a large socio-economic toll on patients and their households. This study also highlights the need to incorporate digital health technologies for postoperative follow-up and adjuvant treatment.

Objective: To identify populations at risk for lost to follow-up while undergoing management of brain tumours in a low-resource setting., Methods: A retrospective study was conducted at the neurosurgical centre on patients presenting with a brain tumour from January 1, 2019, to December 31, 2019. Data on demographic characteristics, surgical characteristics, treatment, and outcomes such as mortality status, were collected by manual chart review. LTFU was defined as patients discontinuing clinical follow-up at the institute of surgical consultation within two years from the initial visit. Univariate (odds ratio) and multivariate (b-coefficient) logistic regression were used to determine factors' significance for LTFU., Results: From a total of 2750 patients from 32 centres, 1140 (41.4%) were LTFU during the study period. Of these 1140 LTFU patients, 156 (13.7%) were LTFU without any intervention, 984 (86.3%) were LTFU after the primary surgery, and 872 (76.5%) patients were LTFU without any adjuvant treatment. On univariate analysis annual hospital case volume (p< 0.001), older age group (15-39 years (p=0.037) and ?40 years (p= 0.016)), and non-surgical treatment (p<=0.026) correlated with a higher risk of LTFU. Belonging to the middle-class cohort was correlated with a better chance of follow up (p=0.001). Multivariate analysis demonstrated that larger centres had the largest b-coefficient of 1.53 (95% CI= 1.3-1.8, p< 0.001)., Conclusions: Our study demonstrated that almost half of patients diagnosed with brain tumours were LTFU within two years of diagnosis. Larger centres, non-surgical treatment, and older age seem to be associated with higher LTFU. Identifying vulnerable populations will allow the need-based provision of care and follow-up to improve health outcomes.

Objective: To enumerate the burden of ependymoma in our region and identify the demographic, tumoural, surgical, clinical characteristics, and outcomes of patients diagnosed with ependymoma., Methods: This retrospective cross-sectional study included patients admitted under neurosurgical service between January 1 and December 31, 2019. The inclusion criterion for the study was a histopathological diagnosis of the brain lesion. The experience of the ependymal brain tumours observed at the 32 participating sites in Pakistan is presented., Results: A total of 2750 patients with brain tumours were seen in 2019 at our centres of whom 58(2.1%) had a histopathological diagnosis of ependymoma. The median age at diagnosis was nine (IQR= 4.5-24.5) years. The median time to surgery from date of radiological diagnosis was 38.5 (IQR= 4-93.8) days. The median KPS score at presentation was 70 (IQR= 60-80), and post-surgery was 90 (IQR= 70-100), showing an average increase of 20. Our population's overall mortality rate for ependymoma was 31.1%, with the 30-day mortality rate being 2.2% (lower than the 4.5% on average for all brain tumours in our cohort)., Conclusions: Ependymomas were predominantly found in the paediatric population in the presented cohort. While gender distribution and histopathological grading seemed to follow international trends, this study had a much higher mortality rate and a much lower gross total resection rate than centres in high-income countries.

Objective: To ascertain the age and gender differences, treatment, and management of meningiomas across Pakistan.., Methods: Data were collected as part of the PBTES, and patients with a histopathological diagnosis of an intracranial meningioma in 2019 that presented at these centres were included in this cohort study sub-analysis. Thirty-two centres participated in the study. Medical students, residents, and faculty collated data from medical records., Results: Our data indicate that meningiomas constitute 15.6% of all intracranial tumours in Pakistan and occur more often in females (236, 55%) than in males. The mean age at diagnosis was 43.7 ± 19.9 years. Meningiomas had a slightly higher preponderance in the right hemisphere of the brain at 203 (47.32%) tumours and 267 (62.2%) of the tumours in the frontal and parietal lobes. We found that 174 (61.3%) of all meningiomas diagnosed in Pakistan in 2019 were grade I tumours, which was also the most commonly occurring tumour grade. Adjuvant chemoradiotherapy for meningiomas was rarely observed in Pakistan., Conclusions: The PBTES reveals a low hospital-based incidence of meningiomas in 2019 when compared to the incidence in high-income countries but found evidence similar to those of other LMICs. Tumour characteristics, such as location, grading and surgical procedures, were similar to global literature.

Objectives: To combat the lack of brain tumour registries, the Pakistan Brain Tumour Epidemiology Study (PBTES) was conducted without any funding from an external source., Methods: A retrospective analysis of patient data, including patients of all age groups diagnosed with all histopathological types of brain tumours from all over Pakistan, was performed. For this, Pakistan Brain Tumour Consortium (PBTC) was established, including 32 neurosurgical centres from around the country. Data was collected online through a proforma that included variables such as patient demographics, clinical characteristics, operative details, postoperative complications, survival indices, and current functional status. The data collection and analysis team included principal investigators, core leads, regional leads, regional associates, and student facilitators. Despite logistical concerns and lack of resources, the PBTES was conducted successfully, and a formal brain tumour surveillance database was formed without any external funding, which remains unheard of., Conclusions: The methods applied in this study are reproducible and can be employed not just to develop more robust brain tumour and other cancer registries but also to study the epidemiology of communicable and non-communicable diseases in resource-limited settings, both locally and globally.

Objective: To explore the differences in demographic, surgical, and prognostic characteristics between the two genders in patients with brain tumours in Pakistan., Method: This study was a retrospective cross-sectional analysis of patients with a histopathological brain tumour diagnosis across 32 high-volume hospitals in Pakistan. The study period was from January 1, 2019, to December 31, 2019. There were no restrictions on inclusion apart from time.., Results: From 2750 patients enrolled in the study, 1605 (58.4%) were male, and 1142 (41.6%) were female . The median age amongst males was 36 (24-49), while the median age amongst females was 37 (24-48). The ratio of married to unmarried patients was 2.7:1 for females and 1.3:1 for males. Surgical treatment was carried out for 1430 (58.1%) males and 1013 (41.9%) females. The median time to surgery was 25 (4-107) days for males and 31 (5-98) days for females. The greatest disparity in tumour malignancy was in grade IV gliomas., Conclusions: Males generally have a higher incidence of brain tumours in our experience, apart from meningiomas, which favour females. The mortality rate and glioblastoma incidence rate are both higher amongst males. However, post-treatment cure is also witnessed. Sociocultural norms play a prominent role in accessing healthcare. Women are generally at a disadvantage compared to their male counterparts, which may impact reporting of brain tumour cases and treatment outcomes.

Background No scoring system is available to predict the extent of resection of giant pituitary adenomas (GPAs) based on magnetic resonance imaging (MRI) parameters. We developed a novel AKU Giant Pituitary Adenoma (AGPA) score and assessed the predictive ability of the scoring system concerning the extent of resection of GPAs. Methodology We retrospectively collected data of patients presenting with GPAs and used our scoring system to assess the surgical resection of these tumors. The Lundin-Pederson (ABC/2) method was used to calculate the pre- and post-resection tumor volume. The relationship between the extent of resection and the AGPA score was assessed using linear regression. The AGPA score considered the tumor's extension into various planes. The maximum total score was 9. Results The scoring system was applied to 45 patients with GPA who underwent surgical resection. The mean resected tumor volume (%) was 82.0 ± 16.7, and the overall mean AGPA score was 4.2 ± 0.8. The pairwise correlation between the resected tumor volume and the overall AGPA scores showed a strong inverse association (r = -0.633, p < 0.001). A significant difference was detected between the estimated scores of 3 and 5 and 4 and 5 (p < 0.001). Conclusions AGPA score is inversely related to the extent of the tumor to be resected, which would help surgeons predict the amount of tumor resection possible as well as predict the difficulty of surgery and plan optimal preoperative patient counseling. In addition, it can predict if staging and a transcranial approach are required., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Enam et al.)

Background and aim Reoperation rate is defined as the percentage of patients returning to the operating room (OR) within 30 days of an initial craniotomy and undergoing a repeat (redo) craniotomy procedure. It is a key factor of quality-of-care assessments and has implications for outcomes, especially in oncological cases. Redo craniotomies are associated with improvement in neurological status and decreased mortality rate compared to non-surgical interventions but are associated with higher costs and risk of complications. It is important to gauge the indications and frequency of redo craniotomies as an index of quality of healthcare to improve patient outcomes. This study aimed to identify the indications, frequency, and outcomes of reoperation following an initial craniotomy in neurosurgical patients at a tertiary care hospital. Methods This retrospective cohort study was conducted at a tertiary care center in Pakistan and included all patients who underwent unplanned reoperation within 30 days of initial craniotomy from January 1, 2010, to December 31, 2017. Demographics, indications for index surgery as well as reoperation, and outcomes in the form of complications, neurological status, and mortality were collected from medical charts and analyzed. Results The study comprised 111 patients who underwent reoperations. Median age of the patients was 36 years (interquartile range {IQR}: 33 years). From a total of more than 1900 annual cases, the frequency of unplanned reoperations was 3.5%. The most common indication of unplanned reoperation based on MRI/CT was hemorrhage (40%, subdural hemorrhage was most common), followed by hydrocephalus (22%), cerebral edema (13%), and residual tumor (13%). The most common clinical reason for unplanned reoperation was a drop in Glasgow Coma Scale (GCS) (59%), whereas anisocoria was seen in 10.8% of patients. The highest mortality rate was observed in patients who were reoperated from post-operative day two to post-operative day seven (56%). Hypertension (p=0.014) and thrombocytopenia (p<0.001) showed significant associations with developing intracranial hemorrhage. Seventy-eight percent of patients showed significant improvement in their Karnofsky Performance Score (KPS) whereas 22% showed deterioration in their KPS. Conclusion The delivery of consistent quality healthcare relies on early detection and intervention in at-risk patients. Our center's reoperation rate is consistent with the average range among other centers globally. Hypertension, anticoagulation, and antiplatelet therapy were common risk factors for redo craniotomies within 30 days. Patients with these conditions need special care to prevent returns to the operating room. Patients also need to be monitored for hemorrhage in the short term (one to two days) and hydrocephalus in the long term (two to 30 days) to intervene early if needed., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Raghib et al.)

The relationship between environmental factors and child health is not well understood in rural Pakistan. This study characterized the environmental factors related to the morbidity of acute respiratory infections (ARIs), diarrhea, and growth using geographical information systems (GIS) technology. Anthropometric, address and disease prevalence data were collected through the SEEM (Study of Environmental Enteropathy and Malnutrition) study in Matiari, Pakistan. Publicly available map data were used to compile coordinates of healthcare facilities. A Pearson correlation coefficient ( r ) was used to calculate the correlation between distance from healthcare facilities and participant growth and morbidity. Other continuous variables influencing these outcomes were analyzed using a random forest regression model. In this study of 416 children, we found that participants living closer to secondary hospitals had a lower prevalence of ARI ( r = 0.154, p < 0.010) and diarrhea (r = 0.228, p < 0.001) as well as participants living closer to Maternal Health Centers (MHCs): ARI ( r = 0.185, p < 0.002) and diarrhea ( r = 0.223, p < 0.001) compared to those living near primary facilities. Our random forest model showed that distance has high variable importance in the context of disease prevalence. Our results indicated that participants closer to more basic healthcare facilities reported a higher prevalence of both diarrhea and ARI than those near more urban facilities, highlighting potential public policy gaps in ameliorating rural health.

Background: Glioblastoma multiforme (GBM) is the most malignant, aggressive and common form of primary brain cancer. Currently, GBM is considered to be a homogenous mass as all its margins are treated equally at the time of resection. However, it is not known whether radiologically distinct regions of GBM are also distinct at molecular level. We conducted this study to see if radiologically distinct regions were also different at the molecular level., Methods: In 20 patients, MRI derived variance known as Apparent Diffusion Coefficient (ADC) was plotted against Contrast Enhancement (CE). Four radiologically distinct regions were identified: 1) high ADC and low CE; 2) low ADC and low CE; 3) high ADC and high CE; and 4) low ADC and high CE. Biopsy samples were collected from these four regions of interest in each patient and immunohistochemistry was conducted to characterize cellular features and identify oncogene and stem cell marker expressing cells., Results: Markedly increased nuclear pleomorphism, cellularity and necrosis were seen in region 2. Oncogene IDH was expressed in all regions, however, it was highest in region 4. Stem cell marker, CD44 expression was highest in region 1 and lowest in region 2 and 3. The expression of CD133 was highest in region 3., Conclusions: This study shows that ADC/CE plot can divide GBM into four regions, whose heterogeneity is evidenced by differential expression of nuclear pleomorphism, necrosis, cellularity and mitotic rate as well as the expression of oncogene and stem cell markers.

Introduction: Calcified cerebral emboli (CCE) are rarely responsible for large vessel occlusion (LVO) in acute anterior stroke, and therefore therapeutic experience is scarce. We sought to expand current knowledge upon therapeutic options with three new cases and a review of current literature., Methods: Systematic search of patients with acute anterior stroke due to LVO in one comprehensive stroke center throughout a 4 year period. Literature search for reported cases of CCE., Results: In total, 21 cases (19 found in literature and 3 from our institution) are reported with a median age of 72 years (interquartile range [IQR] 63-80). Eleven patients were treated acutely, 4 of them with endovascular thrombectomy (EVT). Middle cerebral artery (MCA) M1 was the most affected segment and large artery atherosclerosis (LAA) and cardioembolism (CE) was causative in 41% of cases. EVT was significantly superior to intravenous recombinant tissue plasminogen activator (rtPA) at p = .048 (Fisher's exact test, chi square 6.7)., Conclusions: Given the small sample reported in literature and no reported randomised studies, definitive recommendations could not be reached. However, considering thrombus composition, thrombolysis is most probably not sufficient and priority should be given to EVT., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Anterior cervical discectomy and fusion (ACDF) for cord compression is a safe and effective procedure with good outcomes. However, worsening of myelopathy is the most feared adverse event of the surgery. We report the case of a 36-year-old male patient who presented with an acute non-traumatic C5-6 cervical disc herniation causing incomplete quadriparesis. He underwent an uncomplicated ACDF at C5-6, and after an initial period of improvement, he developed a delayed onset of an anterior cord syndrome on day 3, without any discerning cause. We have reviewed similar cases reported in the literature and believe that our patient's postsurgical course is consistent with a delayed ischaemic/reperfusion injury to the cord following surgical decompression and restoration of blood flow through the anterior spinal artery and we make suggestions for management of such clinical events., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Isolated Hemimegalencephaly (iHME) is a rare form of congenital malformation of cortical development.It is characterized by enlargement of all or part of one cerebral hemisphere. It typically presents with intractable seizures, mental retardation, developmental delay, contralateral hemiparesis and hemianopia. The patient was a five and half month's old baby girl who presented first with focal seizures at 10th day of life. No other physical or behavioral abnormality was noted. However, Initial EEG showed excessive sharp EEG transients more over the right hemisphere, repeated EEG showed spikes, polyspikes, sharps and slow wave discharges predominately over right hemisphere. MRI brain showed asymmetric enlargement of the right cerebral hemisphere, suggestive of hemimegalencephaly. Initial treatment with anti-epileptics was successful in controlling the seizures but later on the seizures became intractable even on polytherapy. Identification of this and similar cases of iHME can help us better understand this disorder and its associated symptoms and eventually help us develop better treatment options for it.

Background/aims: South Asia is an enigma for gastric cancer (GC) because it is a low risk region with a high prevalence of Helicobacter pylori (H. pylori) infections. We evaluated the trend of GC clinical presentation and risk factors in patients with dyspeptic symptoms., Materials and Methods: The medical records of patients, coded by the international classification of diseases (ICD-10-CM, 2015, Diagnosis Code C16.9) for malignancies of stomach diagnosed by esophagogastroduodenoscopy (EGD) and histopathology, were studied., Results: 394 GC cases with a mean age of 54±15 years, range of 18 to 88, were analyzed. 256 (65%) were male. Distal non-cardiac and cardiac tumors were 302 (77%) and 92 (23%) cases, respectively. The WHO classification of GC defined 222 (56%) cases as intestinal type adenocarcinoma, 68 (17%) cases as signet ring cell carcinoma (SRC), 62 (16%) cases as diffuse type and 42 (11%) cases as B cell non-Hodgkin lymphoma. The co-morbid conditions associated with GC were H. pylori infection (positive in 246 (62%) cases), diabetes mellitus type 2 (in 90 (23%) cases), and cigarette smoking (in 94 (24%) cases). Of the male patients, 88 (34%) (p<0.001) were smokers. Body mass index was abnormal in all age groups and in both sexes. Cardiac regions for GC were more common in the 46- to 60-year old age range and in males. Diffuse GC was seen in all age groups but there were significantly more common in the 18- to 45-year old age range. Gastric non-Hodgkin's lymphoma was seen at an early age of 18-45 years in 14(12%) and a later of 61-88 years in 20 (15%)., Conclusion: Intestinal type GC is common at all ages but SRC and diffuse GC are more common in patients less than 50 years old. SRC and diffuse GC were not specific to the elderly in our study population.

A 52-year-old white male presented with an acute onset of slurred speech along with hypoesthesia in the entire left arm. The acute computed tomography (CT) showed relative hypodensity in the intracranial segment of left vertebral artery (VA) that was not present in historical images, pointing to the possible lack of flow. The site of occlusion was confirmed by magnetic resonance imaging (MRI) that showed susceptibility effect in the affected artery. By means of historical native CT comparison the site of VA thrombosis was correctly predicted. Local atherosclerotic thrombosis of the VA could be relatively hypodense on native CT and still have positive susceptibility weighted imaging (SWI) sign., Competing Interests: The authors declare that they have no competing interests.