Clinico-radiological parameters, biochemical and molecular alterations predicting remission and recurrence after surgical treatment of corticotroph adenomas - Cushing's disease.

OBJECTIVES: Endonasal endoscopic transsphenoidal surgery (TSS) and resection of pituitary adenomas is considered to be the gold standard treatment for Cushing's Disease (CD). Even with various recent advances in management, disease persistence and recurrences 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 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-kB and SHH pathway activation and to study the protein expression levels of activation markers of these pathways viz. 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 Cushing's disease was ambispectively analysed with a median follow up of 8.1 years (1-13.29 years). The preoperative clinical, biochemical, radiological features, operative findings, postoperative clinical and biochemical data, histopathological and molecular profile, were retrieved from electronic records. The patients were followed up to assess the remission status. RESULTS: Among the 174 surgeries performed, 140 were primary surgeries, 22 were revision surgeries, 24 surgeries were for paediatric patients and 12 surgeries were performed in patients with Nelson syndrome. In the primary surgery cohort, 74.3% were females and the average age was 28.73 years (SD 10.15). 75% of the patients experienced remission after primary surgery compared to 47.4% in revision surgery. The remission rate in paediatric patients was 55.5%. Post-operative day 1 plasma cortisol (p<0.001; AUC 0.8894 [0.8087-0.9701]) and ACTH (p<0.001; AUC 0.9 [0.7386-1]) levels were seen to be strong independent predictors of remission in the primary surgery cohort. Remission rates after Endoscopic TSS were more than that after microscopic TSS, in patients undergoing primary surgery (81.08% vs 57.14%; p=0.008). Presence of adenoma on histopathological examination (HPE) was also a strong predictor of disease remission (p=0.020). On categorising based on surgical approach and HPE, microscopically operated patients without histopathological evidence of adenoma had significantly higher odds of non-remission (OR 38.1 95% CI 4.2-348.3) compared to endoscopically operated patients with adenoma on HPE. Lower immune reactivity score (IRS) of NR4A1 was found to correlate with higher remission rates (p=0.074). However, none of the molecular markers studied viz. c-Fos , c-Jun, GLI-1, pMEK and p44 showed a significant correlation with the preoperative cortisol values. CONCLUSION: Remission rate after primary surgery is higher as compared to that after revision surgery, and that in paediatric patients is lower as compared to adults. Post-operative day 1 plasma cortisol and ACTH levels are strong independent predictors of remission in the primary surgery cohort. Endoscopic approach with histopathological evidence of adenoma is associated with a higher remission rate and thus endoscopy should be the approach of choice in these patients with the goal of identification of an adenoma on histopathological analysis.

Functional and Neuropsychological Outcome After Surgical Treatment of Moyamoya Disease.

BACKGROUND: Moyamoya disease (MMD) is a rare cerebrovascular disease characterized by progressive stenosis of the supraclinoid internal carotid artery. As a result of chronically decreased brain perfusion, eloquent areas of the brain become hypoperfused, leading to cognitive changes in patients. Repeated infarcts and bleeds produce clinically apparent neurologic deficits. OBJECTIVES: 1) To study the functional and neuropsychological outcome in MMD after revascularization surgery. 2) To find postrevascularization correlation between functional and neuropsychological improvement and radiologic improvement. METHODS: A single-center prospective and analytic study was carried out including 21 patients with MMD during the study period from March 2021 to December 2022. Patients were evaluated and compared before and after revascularization for functional, neuropsychological, and radiologic status. RESULTS: Postoperative functional outcome in terms of modified Rankin Scale score showed improvement in 33.33% of cases (P = 0.0769). An overall improving trend was observed in different neuropsychological domains in both adult and pediatric age groups. However, the trend of neuropsychological improvement was better in adults compared with pediatric patients. Radiologic outcome in the form of the Angiographic Outcome Score (AOS) significantly improved after revascularization (P = 0.0001). There was a trend toward improvement in magnetic resonance imaging (MRI) perfusion in the middle cerebral artery and anterior cerebral artery territories, 4.7% (P = 0.075) and 9.33% (P = 0.058) respectively, compared with preoperative MRI perfusion. CONCLUSIONS: After revascularization, significant improvement occurred in functional and neuropsychological status. This result was also shown radiologically as evidenced by improvement in MRI perfusion and cerebral angiography.

Innovations in craniovertebral junction training: harnessing the power of mixed reality and head-mounted displays.

OBJECTIVE: The objective of this study was to analyze the potential and convenience of using mixed reality as a teaching tool for craniovertebral junction (CVJ) anomaly pathoanatomy. METHODS: CT and CT angiography images of 2 patients with CVJ anomalies were used to construct mixed reality models in the HoloMedicine application on the HoloLens 2 headset, resulting in four viewing stations. Twenty-two participants were randomly allocated into two groups, with each participant rotating through all stations for 90 seconds, each in a different order based on their group. At every station, objective questions evaluating the understanding of CVJ pathoanatomy were answered. At the end, subjective opinion on the user experience of mixed reality was provided using a 5-point Likert scale. The objective performance of the two viewing modes was compared, and a correlation between performance and participant experience was sought. Subjective feedback was compiled and correlated with experience. RESULTS: In both groups, there was a significant improvement in median (interquartile range [IQR]) objective performance with mixed reality compared with DICOM: 1) group A: case 1, median 6 (IQR 6-7) versus 5 (IQR 3-6), p = 0.009; case 2, median 6 (IQR 6-7) versus 5 (IQR 3-6), p = 0.02; 2) group B: case 1, median 6 (IQR 5-7) versus 4 (IQR 2-5), p = 0.04; case 2, median 6 (IQR 6-7) versus 5 (IQR 3-7), p = 0.03. There was significantly higher improvement in less experienced participants in both groups for both cases: 1) group A: case 1, r = -0.8665, p = 0.0005; case 2, r = -0.8002, p = 0.03; 2) group B: case 1, r = -0.6977, p = 0.01; case 2, r = -0.7417, p = 0.009. Subjectively, mixed reality was easy to use, with less disorientation due to the visible background, and it was believed to be a useful teaching tool. CONCLUSIONS: Mixed reality is an effective teaching tool for CVJ pathoanatomy, particularly for young neurosurgeons and trainees. The versatility of mixed reality and the intuitiveness of the user experience offer many potential applications, including training, intraoperative guidance, patient counseling, and individualized medicine; consequently, mixed reality has the potential to transform neurosurgery.

Neurosurgery as a Top-Drawer Choice for Residency in India: Reality or Myth?

INTRODUCTION: This survey was conducted to explore the perceptions of undergraduate (UG) medical students regarding enrolling in a neurosurgical training program. The purpose was to understand' expectations, reasons, apprehensions, and variables influencing students' decisions to pursue a career in neurosurgery. The results shed light on students' perceptions and can help educational institutions and training programs draw in and encourage aspiring neurosurgeons. METHODS: A 35-point online questionnaire was created using Google Forms (Google LLC) after content and face validation and circulated using social media platforms among various public medical colleges across India. Responses were collected over a period of 3 months, from February 2023 to April 2023. A 5-point Likert scale was used to collect the responses wherever applicable. RESULTS: A total of 1042 respondents from 47 medical colleges completed the survey. The majority of the students were not exposed to neurosurgery during their UG program, but despite this, 60.1% (n = 627) were willing to consider it as their career option. Around 91.4% of the respondents perceived neurosurgery to be a challenging but prestigious specialty that has a long learning curve and the worst work-life balance when compared with other specialties. The majority of the respondents (strongly disagree = 24.3%, n = 253; disagree = 31.7%, n = 330) did not view neurosurgery as a male-dominated specialty. Most students preferred a 6-year training program over a 3-year program (P = 0.001) if their medical college had such a course. CONCLUSIONS: Our study reveals that although a majority of the UG students would like to join neurosurgery residency, there are significant barriers in the form of less exposure, negative perceptions, and apprehensions toward the branch. Enhancing medical students' awareness about neurosurgery necessitates the integration of hands-on workshops, simulation-based training, didactic lectures, and neurosurgery rotations into the UG curriculum.

Dorsal bony spur in pediatric split cord malformations: eight-year experience from a tertiary care hospital.

INTRODUCTION: Dorsal spurs in Type I split cord malformations (SCM-I) are infrequent findings. The pathogenesis of the same is debatable. The objective of this study is to analyze our experience with SCM-I patients having dorsal bony spurs. METHODOLOGY: Retrospective analysis of SCM patients operated from 2010 to 2017 was performed. Their demographic profile, clinic-radiological features, operative findings, and outcome following surgery were recorded. RESULTS: Twenty-four cases of Type I SCM harboring dorsal bony spurs were identified with mean age of 4.96 years. The commonest split site was lumbar, documented in 62.5%. Scoliosis was observed in 58.3%. Pre-operative neurological deficits were seen in 66.6% cases with asymmetric weakness of limbs seen in 16.6%. There was no new neurological deficit observed post-operatively. CONCLUSIONS: This is the largest series of dorsal spurs occurring in SCM, reported in literature so far. Meticulous pre-operative evaluation and imaging are important to identify dorsal spurs for appropriate management and good clinical outcome. Differentiating dorsal spur from ventral spur is important as it has a bearing on surgical approach.

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.

Virtual Reality in Preoperative Planning of Complex Cranial Surgery.

OBJECTIVE: Changing paradigms of neurosurgical training and limited operative exposure during the residency period have made it necessary to evaluate newer technologies for training. Virtual reality (VR) technology provides three-dimensional reconstruction of routine imaging, along with the ability to see as well as interact. The application of VR technology in operative planning, which is an important part of neurosurgical training, has been incompletely studied so far. METHODS: Sixteen final-year residents, post-M.Ch. (magister chirurgiae) residents, and fellows were included as study participants. They were divided into 2 groups based on their seniority for further analysis. Five complex cranial cases were selected and a multiple-choice question-based test was prepared by the authors, with 5 questions for each of the cases. The pretest score was determined based on performance on the test after participants accessed routine preoperative imaging. The posttest score was calculated after use of the VR system (ImmersiveTouch VR System, ImmersiveTouch Inc.). Analysis was performed by the investigators, who were blinded to the identity of the participant. Subanalysis based on the type of case and type of question was performed. Feedback was obtained from each participant regarding VR use. RESULTS: There was an overall improvement in scores from pretest to posttest, which was also noted in the analysis based on the participants' seniority. This improvement was noted to be more for the vascular cases (15.89%) compared with the tumor cases (7.84%). Participants also fared better in questions related to surgical anatomy and surgical approach, compared with questions based on the diagnosis. There was overall positive feedback from participants regarding VR use, and most participants wanted VR to become a routine part of operative planning. CONCLUSIONS: Our study shows that there is improvement in understanding of surgical aspects after use of this VR system.

Technical Nuances and Complication Avoidance in Surgery for Medullary Hemangioblastoma.

Hemangioblastomas are benign World Health Organization grade 1 tumors that are relatively rare.1 They may be sporadic or found in association with von Hippel-Lindau disease. Posterior fossa hemangioblastomas arise in the cerebellar hemisphere and, less commonly, at other sites such as medullary hemangioblastomas.2-4 Their characteristic radiologic features including solid-cystic morphology and prominent vessels aid in the preoperative diagnosis.5 In this operative video, we discuss the technical nuances and steps to avoid complications while operating on a large medullary hemangioblastoma. A 19-year-old lady presented with headache, vomiting, and visual deterioration of 2 months' duration. On examination, she had visual acuity of 4/60 right side, 6/60 left side, bilateral papilledema, and truncal and gait ataxia. Since she had presented in altered sensorium and a computed tomography head scan showed hydrocephalus, a ventriculoperitoneal shunt was placed on an emergency basis. Proper radiologic workup was done. On the basis of radiologic findings, she was provisionally diagnosed to have hemangioblastoma and surgery was planned. Preoperative angiogram showed an intense tumoral blush, but embolization was deemed infeasible since the tumor had multiple feeding vessels. Definitive surgery for tumor excision was performed 5 days after the shunt surgery. The patient's family consented to the procedure and the use of images and clinical data for publication. Video 1 highlights the tumor location, its prominent blood supply and venous drainage, use of intraoperative neuromonitoring, and the technical nuances for an en bloc excision. The patient had a left lateral gaze (sixth nerve) palsy in the immediate postoperative period, which resolved over the next 3 months. Postoperative and follow-up imaging confirmed complete tumor excision. Modern microsurgical techniques and a thorough understanding of the tumor vasculature help in performing safe and complete excision of such tumors.1,2 En bloc excision remains the mainstay of surgery for hemangioblastomas.

SimSpine: A Cost-Effective Spinal Endoscopy Training Prototype for Neurosurgical Residents Skills Training.

OBJECTIVE: To compare the SimSpine (indigenously developed, low-cost model) and EasyGO! (Karl Storz, Tuttlingen, Germany) systems for simulation of endoscopic discectomy. METHODS: Twelve neurosurgery residents, 6 in postgraduate years 1-4 or equivalent (junior) and 6 in postgraduate years 5-6 or equivalent (senior), were randomly allocated (1:1) to either EasyGO! or SimSpine endoscopic visualization systems for endoscopic lumbar discectomy simulation on the same physical simulator. After the first exercise, the participants switched over to the other system, and the exercise was repeated. Time taken to dock the system, time to reach annulus, time required for task completion, dural violation, and volume of disc material removed were used for calculating objective efficiency score. Subjective scoring (Neurosurgery Education and Training School [NETS] criteria) was performed by 4 blinded mentors based on recorded video on 2 separate occasions 2 weeks apart. Cumulative score was calculated based on efficiency and Neurosurgery Education and Training School scores. RESULTS: Performance metrics were similar across the 2 platforms, regardless of participant seniority (P > 0.05). Time to reach disc space and discectomy time improved for both EasyGO! (P = 0.07 and P = 0.03, respectively) and SimSpine (P = 0.01 and P = 0.04, respectively) between first and second exercises. Efficiency and cumulative scores were better (P = 0.04 and P = 0.03 respectively) when EasyGO! was used as the first device compared with SimSpine. CONCLUSIONS: SimSpine is a cost-effective viable alternative to EasyGO for endoscopic lumbar discectomy simulation-based training.

Correlation of Surgical Outcomes of Petroclival Meningiomas with Clinicoradiologic Parameters and Molecular and Chromosomal Alterations.

OBJECTIVE: To identify clinical, radiologic, intraoperative, histopathologic, and molecular factors that might affect the surgical outcome of petroclival meningiomas. METHODS: Medical records of 53 cases of petroclival meningiomas operated from 2003 to 2021 were reviewed for clinicoradiologic and molecular factors that were correlated with extent of resection. RESULTS: Modified Dolenc-Kawase anterior transpetrous rhomboid (44, 83.0%) was the most commonly used approach, followed by retrosigmoid (2, 3.8%) and combined (7, 13.2%) approaches. Hypointense tumors on T2-weighted magnetic resonance imaging (odds ratio [OR] 5.85; 95% confidence interval [CI] 1.70-20.41) and presence of brainstem edema (OR 4.53; 95% CI 1.36-15.12) were found to be significant factors increasing the likelihood of subtotal resection (STR; P = 0.004 and P = 0.011, respectively). In the presence of both tumor T2 hypointensity and brainstem edema, there was a significant increase in the likelihood of STR (P = 0.001; OR 25; 95% CI 3.52-177.48). Of the 16 cases for which molecular analysis was performed, no specimen was found to have pTERT, AKT-1 E17K, and SMO L412F and W535L mutations. All (100%) the patients harboring H3K27me3 loss and/or hemizygous CDKN2A deletion had cavernous sinus extension compared with 62.5% of patients without H3K27me3 loss and 72.7% with hemizygous CDKN2A retention. Similarly, hemizygous CDKN2A deletion and H3K27me3 loss were associated with an increase in the rate of brainstem edema from 27.3% to 60% and 25% to 50%, respectively. CONCLUSIONS: T2 hypointense tumor and brainstem edema on preoperative imaging are significant predictors of STR. H3K27me3 loss and hemizygous CDKN2A deletion may be associated with cavernous sinus extension, suggesting their role in tumor spread.

Factors associated with hearing outcomes after a middle fossa approach in 131 consecutive patients with vestibular schwannomas.

OBJECTIVE: The middle fossa approach is an effective option for the treatment of small (Koos grade I and II) vestibular schwannomas (VSs) when the goal is hearing preservation. The authors evaluated the rates of hearing preservation and examined the factors associated with improved hearing outcomes after the middle fossa approach for VSs. METHODS: In this retrospective, single-center cohort study evaluating the clinical outcomes after resection of small VSs using the middle fossa approach, consecutive adult patients (> 18 years) who underwent surgery between January 2000 and December 2021 were included. Clinical and imaging characteristics were analyzed, including baseline hearing status, duration of surgery, anesthetic parameters, and imaging characteristics of the surgically treated tumors. RESULTS: Among the 131 included patients, 102 had valid and discoverable pre- and postoperative audiology assessments. The mean follow-up was 26 months (range 1-180 months). There were 85 patients with serviceable hearing preoperatively, defined as American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) class A or B, of whom 78% retained class A or B hearing at the last follow-up. Binary logistic regression demonstrated that preoperative hearing AAO-HNS class (OR 0.19, 95% CI 0.05-0.77; p = 0.02), overlap between fundus and cochlea (OR 0.32, 95% CI 0.11-0.96; p = 0.04), and duration of anesthesia (OR 0.98, 95% CI 0.97-0.99; p = 0.03) were independent predictors of hearing outcomes. Additionally, 75% of patients with high diffusion-weighted imaging signal in the tumor (p = 0.009) and 67% of patients with the tumor originating at the modiolus of the cochlea (p = 0.004) had poor hearing outcomes. CONCLUSIONS: The hearing preservation rates after microsurgical resection of small VSs using the middle fossa approach are high, with 78% of patients maintaining AAO-HNS class A or B hearing. Poor hearing status at baseline, longer duration of anesthesia, and large overlap between the fundus of the internal auditory canal and the cochlea were independently associated with unfavorable hearing outcomes. Imaging characteristics can be used to stratify patients' risk of hearing loss.

Effect of Age, Stage, and Type of Surgical Revascularization on Clinical and Angiographic Outcome in Moyamoya Disease - Experience from a Case Series of 175 Revascularization Procedures.

Background: There is dearth of literature on impact of age - pediatric versus adult, Suzuki staging - early versus late, and revascularization type - indirect versus direct on clinical and angiographic outcome in moyamoya disease (MMD). Hence, we intend to comprehensively evaluate factors influencing outcome in MMD following surgical revascularization. Methods: MMD patients operated at our institute from January 2011 to August 2018 were followed for an average 24 months. Primary outcomes were modified Rankin score (mRS) and stroke risk reduction. Secondary outcome was angiographic outcome score (AOS). Results: A total of 133 patients including 37.6% adults (>18 years; n = 50) underwent 175 revascularizations - 89 direct (DR) and 86 indirect (IR) subgroups. Mean mRS scores improved in pediatric DR (P < 0.001), IR (P < 0.001), adult IR (P = 0.10), and DR (P = 0.25) subgroups. Recurrent stroke rate was similar in pediatric-DR (2.7%) and IR (7.6%, P = 0.61), and adult-DR (0%) and IR (4.1%) subgroups (P = 1.00). AOS scores improved in pediatric DR (P = 0.002) and IR (P = 0.01), and adult-DR (P = 0.02) and IR (P = 0.06) subgroups. Late-stage MMD (Suzuki IV-VI) showed better improvement in mRS scores than early-stage-Suzuki (I-III; P < 0.001). Recurrent stroke rates were similar (P = 0.26) and AOS scores improved significantly in early- and late-stage MMD (P < 0.001). Conclusions: In pediatrics, clinical and angiographic outcome significantly improved after revascularization procedure, and in adults, angiographic improvement was more evident than clinical recovery. Late-stage Suzuki MMD patients demonstrated significantly better clinical improvement than early stage. The angiographic improvement was equivalent to early stage, irrespective of age and type of revascularization.

Modified Dolenc-Kawase anterior petrous rhomboid approach for petroclival meningioma: surgical nuances and complication avoidance.

Resection of petroclival meningiomas has remained challenging because of the critical neurovascular structures that lie in the vicinity, and thus various surgical corridors have been explored over time to figure out the optimum approach. In this video, the authors have highlighted the operative nuances of the modified Dolenc-Kawase (MDK) anterior petrous rhomboid approach. This approach gives access to the prepontine area, Dorello's canal, anterior petrous apex, and upper two-thirds of the clivus with better angulation and surgical flexibility. It is a versatile approach for petroclival lesions that are not extending laterally and inferiorly to the internal auditory canal. The video can be found here: https://stream.cadmore.media/r10.3171/2022.1.FOCVID21256.