Clinicoradiological Parameters and Biochemical and Molecular Alterations Predicting Remission and Recurrence After Surgical Treatment of Corticotroph Adenomas-Cushing Disease.

OBJECTIVE: Endonasal endoscopic transsphenoidal surgery (TSS) and resection of pituitary adenomas are considered the gold standard treatment for Cushing disease (CD). Even with various recent advances in management, disease persistence and recurrence are common in these patients. The remission rate in the global population after surgery has been reported to vary widely from 64% to 93%. This study aims to determine the various clinical, biochemical, radiological, and histological factors that correlate with persistence and recurrence in patients with CD. This study also aims to understand the clinicopathological significance of EGFR-MAPK, NF-κB, and SHH pathway activation and to study the protein expression of activation markers of these pathways (i.e., c-Fos, c-Jun, GLI-1, pMEK, NR4A1, and p44) in functioning corticotroph pituitary adenomas. METHODS: From January 2009 to September 2022, the clinical data of 167 patients who underwent surgical treatment (n = 174 surgeries) for CD with a median follow-up of 8.1 years (range, 1-13.29 years) were ambispectively analyzed. The preoperative clinical, biochemical, and radiological features, operative findings, postoperative clinical and biochemical data, and histopathological and molecular profiles were retrieved from the electronic medical records. The patients were followed up to assess their remission status. RESULTS: Among the 174 surgeries performed, 140 were primary surgeries, 22 were revision surgeries, 24 surgeries were for pediatric patients, and 12 surgeries were for patients with Nelson syndrome. In the primary surgery cohort, 74.3% were female, and the average age was 28.73 ± 10.15 years. Of the primary surgery cohort, 75% of the patients experienced remission compared with 47.4% after revision surgery. The remission rate for the pediatric patients was 55.5%. The postoperative day 1 plasma cortisol (P < 0.001; area under the curve, 0.8894; range, 0.8087-0.9701) and adrenocorticotropic hormone (P < 0.001; area under the curve, 0.9; range, 0.7386-1) levels were seen to be strong independent predictors of remission in the primary surgery cohort. The remission rate after endoscopic TSS was greater than that after microscopic TSS in patients undergoing primary surgery (81.08% vs. 57.14%; P = 0.008). The presence of adenoma on histopathological examination (HPE) was also a strong predictor of disease remission (P = 0.020). On stratifying by surgical approach and HPE, microscopically operated patients without histopathological evidence of adenoma had significantly higher odds of nonremission (odds ratio, 38.1; 95% confidence interval, 4.2-348.3) compared with endoscopically operated patients with adenoma found on HPE. A lower immunoreactivity score for NR4A1 was found to correlate with higher remission rates (P = 0.074). However, none of the molecular markers studied (i.e., c-Fos, c-Jun, GLI-1, pMEK, and p44) showed a significant correlation with the preoperative cortisol values. CONCLUSIONS: The remission rate after primary surgery is higher than that after revision surgery and is lower for pediatric patients than for adults. The postoperative day 1 plasma cortisol and adrenocorticotropic hormone levels are strong independent predictors of remission in the primary surgery cohort. An endoscopic approach with histopathological evidence of adenoma is associated with a higher remission rate; thus, endoscopy should be the approach of choice for these patients with the goal of identification of an adenoma on HPE.

Middle third falcine meningiomas-surgical nuances for cortical venous preservation.

PURPOSE: To improve postoperative outcome in middle third falcine meningiomas by cortical venous preservation. BACKGROUND: Falcine meningiomas arise from the falx and do not involve the superior sagittal sinus (SSS). Their complete resection is often associated with the risk of venous infarction in the eloquent cortex due to overlying superficial cortical veins on the tumors. METHOD: We report one case of middle third falcine meningioma, where we used the posterior interhemispheric corridor for tumor approach. CONCLUSION: Use of the posterior interhemispheric approach, carefully raised bone flap, along with sharp dissection and vein reinforcement using fibrin glue can help to preserve the cortical veins while resecting the falcine meningiomas.

Re-Admissions of 'Unknown' Traumatic Brain Injury Patients - Inadequacy of Rehabilitative Services in a Developing Country.

BACKGROUND: In neurosurgical practice, continuous care after discharge and the ability to detect subtle indicators of clinical deterioration are mandatory to prevent the progression of a disease. The care of 'unknown' patients discharged to rehabilitation homes may not have this privilege, especially in resource-poor countries such as India. OBJECTIVE: We have attempted to study the causes and outcomes of re-admissions of 'unknown' patients with previous traumatic brain injury (TBI) to estimate the quality of nursing care in our rehabilitation centers. MATERIAL AND METHODS: The electronic hospital records of all consecutive 'unknown' TBI patients with unplanned re-admissions at our institute from January 2014 to December 2018 were retrospectively reviewed and analyzed for the factors determining the risk and outcomes of re-admission. RESULTS: Out of 245 patients sent to rehabilitation homes at discharge, 47 patients (19.18%) were re-admitted. A total of 33 patients (70%) were re-admitted between 1 month and 1 year. Out of these, 38 patients (80.9%) were re-admitted because of preventable causes. Fifteen patients (31.9%) died during the hospital stay. The rest of the 32 (68%) patients were discharged after the management of the concerned condition with an average hospital stay of 9 ± 11.1 days. The average Glasgow coma scale (GCS) at re-admission of the patients who died was 6 (range 3-11). Two patients were brought in the brain dead status, whereas 20 patients (42.6%) had a GCS of 5 or below at the time of re-admission. The risk of mortality among patients with non-preventable causes was 88.9% (8/9) compared to preventable causes 18.4% (7/38). However, preventable causes for re-admission are much more common, resulting in nearly a similar overall contribution to mortality. CONCLUSIONS: There is a high rate of mortality and morbidity in 'unknown' patients with TBI because of poor post-discharge care in developing countries. Because preventable causes are the major contributor to re-admissions, the re-admission rate is a good indicator of a lack of adequate rehabilitative services. The need for improving the post-discharge management of 'unknown' patients with TBI in resource-poor countries cannot be over-emphasized.

Papillary Tumors of Pineal Region: A Single-Center Experience in Management of 11 Cases.

BACKGROUND: Papillary tumors of pineal region (PTPR) comprise a very rare subset of pineal region tumors that have been recently described. Literature on the management and outcome of PTPR is scarce owing to the rarity of these tumors. To address this lacuna, we analyzed our experience in management of PTPR. METHODS: We retrospectively analyzed the outcome of 11 patients with histopathologically proven PTPR who underwent surgical excision at our center. RESULTS: Mean patient age was 33.3 years (range, 12-45 years), and male-to-female ratio was 1.75:1. Headache was the most common presentation followed by visual disturbances, altered sensorium, Perinaud syndrome, and seizures. Cerebrospinal fluid diversion was required in 6 patients. Krause approach was the most common approach used for tumor excision (9/11 cases). There was no perioperative mortality. Two patients were lost to follow-up. In the remaining 9 patients, the average follow-up period was 45 months (range, 12-79 months). On first postoperative magnetic resonance imaging, 8 patients showed no evidence of residual tumor (gross total resection), while 1 patient had small residual tumor (near-total resection) that remained stable during follow-up. Four patients underwent adjuvant chemoradiotherapy. None of the patients developed recurrence during follow-up. CONCLUSIONS: PTPR are a rare subgroup of pineal region tumors with distinct cells of origin but presentation similar to other pineal region tumors. Surgical resection constitutes the mainstay of management, and the extent of resection appears to be the most important determinant of prognosis. The role of adjuvant therapy still needs to be determined.

Management protocol and surgical techniques for MRI-Negative Cushing's disease: a series of 6 cases.

Up to 40% of Cushing's disease (CD) patients show no evidence of an adenoma on dynamic contrast-enhanced MRI. Inferior petrosal sinus sampling (IPSS) remains the gold standard for diagnosis in these patients. Remission rates in MRI-Negative CD are far less at 50%-71%, compared with patients in whom an adenoma is identified on MRI. Endoscopic endonasal transsphenoidal surgery is the surgical approach of choice in these cases. Various adjuncts can be used to localize an adenoma. In this video, the authors highlight their additional usage of pituitary perfusion MRI for identification of the adenoma. They present their stepwise management algorithm and surgical techniques for sellar and suprasellar exploration in 6 cases of MRI-Negative CD operated on by the senior author (A.S.). The video can be found here: https://stream.cadmore.media/r10.3171/2023.4.FOCVID2318.

Ossified upper thoracic intradural mature teratoma in a teenager - A technical case report with special emphasis on surgical strategy.

Spinal teratomas are heterogeneous neoplasms and are extremely rare in the upper thoracic spine. They are sub-classified as mature, immature, or malignant. They may be calcified or rarely ossified; the latter posing a major surgical challenge due to surgical difficulties in safe removal. Clinicoradiologico-pathological and operative experience of ossified spinal intradural mature teratomas is extremely rare. We present a case of ossified upper thoracic intradural mature teratoma managed by microsurgical drilling and resection under neuromonitoring.

Brain Tumor Programs in Asia and Africa: Current Status, Challenges, and Future Perspectives.

OBJECTIVE: To assess the status of brain tumor programs in Asia and Africa and propose comprehensive evidence-based short- and long-term measures for improving the existing systems. METHODS: A cross-sectional analytical study was conducted in June 2022 by the Asia-Africa Neurosurgery Collaborative. A 27-item questionnaire was designed and distributed to gain insight into the status and future directions of brain tumor programs in Asia and Africa. Six components of brain tumor programs were identified-surgery, oncology, neuropathology, research, training, and finances-and assigned scores of 0-14. The total scores allowed subclassification of each country into levels of brain tumor program from I to VI. RESULTS: A total of 110 responses from 92 countries were received. These were subdivided into 3 groups: group 1, countries with response from neurosurgeons (73 countries); group 2, countries with no neurosurgeons (19 countries); and group 3, countries without a neurosurgeon response (16 countries). The components associated with the highest level of brain tumor program were surgery, neuropathology, and oncology. Most countries in both continents had level III brain tumor programs with a mean surgical score of 2.24. The major lag between each group was with respect to the advances in neuropathology and financial support. CONCLUSIONS: There is an urgent need to improve and develop existing and nonexistent neuro-oncology infrastructure, personnel, and logistics in countries across the continents, especially for the countries with no neurosurgeons.

Anterior Petrous Rhomboid Approach for Petroclival Chondrosarcoma.

Access to the petroclival region has always been challenging owing to the surrounding neurovascular structures. The ideal approach to the region depends not only on the specific tumor characteristics, but also on surgeon preference. In this video article, we have highlighted the use of the modified Dolenc-Kawase approach to expand the standard anterior petrosectomy corridor for challenging tumors that need additional exposure.1-5 A 60-year-old woman presented with facial sensory loss and occasional diplopia. On radiological investigation, a densely calcified petroclival lesion was identified (Video 1). A temporal craniotomy with zygomatic osteotomy was performed followed by deroofing of the superior orbital fissure, saucerization of the foramen spinosum, and coagulation and division of the middle meningeal artery. The temporal dura propria was then dissected off the lateral wall of cavernous sinus using a combination of sharp and blunt dissection to expose the modified Dolenc-Kawase rhomboid. A T-shaped dural incision was made along with tentorial sectioning and division of the superior petrosal sinus. Owing to dense calcification in the tumor, a bone Cavitron ultrasonic aspirator (CUSA; Integra LifeSciences, Princeton, New Jersey, USA) was used for debulking of the tumor. Tumor was removed piecemeal alternately using the bone CUSA and scissors. Tumor was dissected from above and below the trigeminal nerve that forms the center of the corridor followed by dissection off the sixth cranial nerve as it enters the Dorello canal. An endoscope may be used at the end to ensure complete removal of the tumor.

Management of Cushing's Disease: Changing Trend from Microscopic to Endoscopic Surgery.

BACKGROUND: Cushing's disease (CD) is a spectrum of clinical manifestations due to adrenocorticotropic hormone-secreting pituitary adenoma. Transsphenoidal adenomectomy remains the standard treatment. There has been a paradigm shift from microscopic to endoscopic transsphenoidal surgery in recent years. However, the efficacy of endoscopic transsphenoidal surgery has not been established. Therefore, it is of interest to determine the superiority of endoscopic transsphenoidal surgery, if any, over microscopic surgery. OBJECTIVE: To assess the efficacy of endoscopic endonasal transsphenoidal surgery for the treatment of CD and to determine the factors affecting remission. METHODS: Patients undergoing surgery for CD from 2009 to 2017 were analyzed retrospectively. Transsphenoidal resection was the preferred treatment, with recent trends in favor of the endonasal endoscopic skull base approach. Postoperative cortisol level of <2 µg/dL was taken as remission and value between 2 and 5 µg/dL as possible remission. RESULTS: In total, 104 patients operated primarily for CD were included for analysis; 47 patients underwent microscopic surgery, 55 endoscopic surgery, and 2 were operated transcranially. Remission was achieved in 76.47% of patients. In univariate analysis, factors significantly associated with remission were 1) type of surgery (P = 0.01); remission in endoscopy surgery (88.23%) is better than microscopy (56.6%); 2) postoperative day 1 morning cortisol (P = 0.004); and 3) postoperative day 1 morning ACTH (P = 0.015). In multivariate analysis, only postoperative day 1 cortisol was found to be significant predictor of remission (P = 0.02). CONCLUSIONS: Postoperative plasma cortisol level is a strong independent predictor of remission. Remission provided by endoscopy is significantly better than the microscopic approach.

Intracranial aspergillosis amongst immunocompetent patients: An experience with combined surgical and medical management of 18 patients.

OBJECTIVE: Fungal infections of central nervous system (CNS) commonly affect immunocompromised patients, however, recently such cases have been reported even amongst immunocompetent patients. PATIENTS & METHODS: In this study, we retrospectively analyzed outcome of 18 immunocompetent patients with histopathologically proven intracranial Aspergillosis undergoing combined surgical and medical management. RESULTS: The age of patients ranged from 5-65 years. Fourteen out of 18 patients had well defined lesions while 4 had diffuse disease. Paranasal sinuses were involved in 8 & cavernous sinus in 3 patients. Six patients had hydrocephalus. Four patients developed infarcts during their clinical course. Surgical interventions included gross (n = 4) or subtotal excision (n = 8), decompressive craniectomy & biopsy of lesion (n = 4), biopsy only (n = 2) and ventriculoperitoneal shunt placement (n = 6). All patients received postoperative antifungal therapy. The duration of follow up ranged from 10-60 months. Overall mortality was 44.4%. Mortality amongst patients undergoing gross total and subtotal excision was 25% & 50% respectively. Patients undergoing DC had a mortality of 25%. Both patients undergoing only biopsy died. Hydrocephalus was associated with a very high mortality (83.3%). Amongst surviving patients (n = 10), 6 patients became disease free & rest 4 had stable disease at last follow up. CONCLUSIONS: Intracranial aspergillosis is associated with high morbidity & mortality even amongst immunocompetent patients. An aggressive multidisciplinary management is thus needed to improve outcome. Our study shows that a combination of surgical excision or decompressive craniectomy and antifungal therapy can be helpful in improving prognosis of these patients.

Retrospective analysis of prevalent anatomy spotter's examination: an educational audit.

PURPOSE: The spotter's (objectively structured practical examination) is an assessment tool which is widely used to test the practical knowledge of anatomy extensively. In Indian context it is used as an inclusive model in the gross anatomy practical examination and the marks allotted to it varies. The traditional spotter examination often has been blamed for only incorporating the initial levels of revised Bloom's taxonomy. This study retrospectively analysed the pre-professional spotter's examination score and tested its efficacy in terms of reliability, internal consistency, validity, educational impact, and resource intensiveness. METHODS: The summative data of student's score on four different days of unrepeated spotter's examination and final theory examination score was collected and tabulated. These four group of students acted as independent cohorts. The difficulty index (DI), point biserial correlation (PBC), Cronbach α (CA) and descriptive statistics of each cohort were calculated. Revised bloom taxonomy rating was applied to spotter's. RESULTS: We found heterogenous distribution of spotter's in each cohort according to DI. The PBCs and CA of each cohort were acceptable. The majority of spotter's tested the cognitive and comprehension domain of revised bloom's taxonomy. There was nonsignificant difference between mean scores of cohorts but we found low positive significant correlation between theory and spotter's score. CONCLUSION: We concluded that the construct of spotter's was reliable, internally consistent, had fair validity, variable educational impact, and sustainable resource intensiveness. We propose urgent redesigning of spotter's to include higher level of taxonomy to comply with emerging curricular changes.