Duodenal quantitative mucosal morphometry in children with environmental enteric dysfunction: a cross-sectional multi-country analysis.

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. OBJECTIVE: 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 to NPA or celiac disease, and identify associations between morphometry and histology or immunohistochemistry amongst 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 semi-quantitative 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. While acknowledging the challenges with obtaining relevant tissue, these data form the basis for further assessments of the role of morphometry in EED.

The effect of ocrelizumab on Balo's tumefactive lesion: A case report.

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 (1H-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 mm2/s) to 6-month follow-up (1.037 × 10-3 mm2/s), while the 12-month follow-up MD was 1.086 × 10-3 mm2/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.

Choroid plexus volume as a marker of retinal atrophy in relapsing remitting multiple sclerosis.

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 (r2 = 0.25, p = 0.0002), disease duration (r2 = 0.30, p = 0.01), and T2 lesion volume (r2 = 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.

From Animal Models to Clinical Trials: The Potential of Antimicrobials in Multiple Sclerosis Treatment.

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.

Role of white matter in cognitive impairment among relapsing remitting multiple sclerosis patients.

BACKGROUND: Multiple Sclerosis (MS) associated cognitive impairment is believed to be mostly connected with damage to gray matter. The contribution of white matter is still poorly understood. We aim to examine the relationship between cognition and white matter tracts among relapsing remitting MS (RRMS) patients. METHODS: Thirty RRMS patients were selected undergo the (3-seconds-interstimulus-interval paced auditory serial addition test) PASAT-3, the (symbol digit modalities test (SDMT) and full-brain MRI scans on a SIEMENS 3 Tesla Verio scanner. Diffusion Tensor Imaging (DTI) parameters, such as fractional anisotropy (FA) and mean diffusivity (MD) were examined in 37 white matter (WM) tracts. WM tracts were selected from the association pathways, projection pathways, commissural pathways by applying Human Connectome project (HCP)842 tractography atlas after DTI data reconstruction and registration to HCP1065 diffusion template in DSI Studio (version March 2021) In SPSS v26, Spearman's rank correlation analysis was used to examine the connection between DTI WM tracts and cognitive scores. The power of the study was increased by using false discovery rate (FDR) software. RESULTS: The mean scores on the PASAT-3 and SDMT were 31.5 ± 12.8 and 46.9 ± 16.7 respectively. Better cognitive performance was correlated to higher FA values, while lower cognitive function was correlated to higher MD values. There was a positive correlation between FA values in the right medial lemniscus and superior cerebellar peduncle and SDMT scores (p 0.05). Additionally, there was a trend for significance between the FA values in the left corticothalamic tract and SDMT scores. MD values in the superior cerebellar peduncle, left arcuate Fasciculus and left extreme capsule were negatively correlated with SDMT scores (p<0.05). PASAT-3 scores were negatively correlated with MD values in the right cerebellum, however, there was no significant correlation between PASAT-3 and FA values. CONCLUSIONS: White matter tracts, particularly the superior cerebellar peduncle, contribute to the cognitive impairment in RRMS. Larger sample sizes for longitudinal research are necessary.

Quantitative Morphometry and Machine Learning Model to Explore Duodenal and Rectal Mucosal Tissue of Children with Environmental Enteric Dysfunction.

Environmental enteric dysfunction (EED) is a subclinical enteropathy prevalent in resource-limited settings, hypothesized to be a consequence of chronic exposure to environmental enteropathogens, resulting in malnutrition, growth failure, neurocognitive delays, and oral vaccine failure. This study explored the duodenal and colonic tissues of children with EED, celiac disease, and other enteropathies using quantitative mucosal morphometry, histopathologic scoring indices, and machine learning-based image analysis from archival and prospective cohorts of children from Pakistan and the United States. We observed villus blunting as being more prominent in celiac disease than in EED, as shorter lengths of villi were observed in patients with celiac disease from Pakistan than in those from the United States, with median (interquartile range) lengths of 81 (73, 127) µm and 209 (188, 266) µm, respectively. Additionally, per the Marsh scoring method, celiac disease histologic severity was increased in the cohorts from Pakistan. Goblet cell depletion and increased intraepithelial lymphocytes were features of EED and celiac disease. Interestingly, the rectal tissue from cases with EED showed increased mononuclear inflammatory cells and intraepithelial lymphocytes in the crypts compared with controls. Increased neutrophils in the rectal crypt epithelium were also significantly associated with increased EED histologic severity scores in duodenal tissue. We observed an overlap between diseased and healthy duodenal tissue upon leveraging machine learning image analysis. We conclude that EED comprises a spectrum of inflammation in the duodenum, as previously described, and the rectal mucosa, warranting the examination of both anatomic regions in our efforts to understand and manage EED.

Prognostic implication of size on outcomes of pituitary macroadenoma: a comparative analysis of giant adenoma with non-giant macroadenoma.

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.

AKU Giant Pituitary Adenoma Score: A Novel Scoring System to Predict the Outcomes of Surgery for Giant Pituitary Adenomas.

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.

Risk Factors and Outcomes of Redo Craniotomy: A Tertiary Care Center Analysis.

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.

The Pakistan Brain Tumour Epidemiology Study.

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.

Conducting the Pakistan brain tumour epidemiology study - report on the methodology.

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.

Factors associated with lost to follow up in patients with brain tumours: A multi-centre study in Pakistan.

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.

Distance travelled for brain tumour surgery: An Low and Middle Income Country's perspective.

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.

Treatment patterns of glioma in Pakistan: An epidemiological perspective.

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.

Schwannoma: A surgical epidemiology.

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.

Ependymoma: an epidemiological perspective from a low- and middle-income country.

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.

Prioritizing Pituitary Adenoma Care in Pakistan: Analysis from an Epidemiological Study.

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.

Meningioma - defining characteristics of the affected Pakistani population.

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.

Craniopharyngioma: A lower-middle-income-country epidemiology.

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.

Metastatic brain tumours in Pakistan: An epidemiological overview.

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.