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.

Analysis of Histomorphologic/Molecular Association and Immune Checkpoint Regulators in Epithelioid Glioblastoma and Pleomorphic Xanthoastrocytoma: Are These Tumors Potential Candidates for Immune Checkpoint Blockade?

Accurate diagnosis of Epithelioid glioblastoma (eGB) and pleomorphic xanthoastrocytoma (PXA) is sometimes challenging owing to overlapping histologic and genetic features. There are limited reports on the immune profile of these tumors. In this study, we assessed 21 PXA [15 PXA Grade 2 (PXAG2); 6 PXA Grade 3 (PXAG3)] and 14 eGB for their histopathological and molecular association. Further, their immune profile was compared with GB, IDH1 wild-type (wt) (n-18). Morphologically, PXAG2 mostly differed from eGB; however, it was occasionally difficult to differentiate PXAG3 from eGB due to their epithelioid pattern and less obvious degenerative features. PXAG2 showed predominantly diffuse, whereas variable positivity for epithelial and glial markers was seen in PXAG3 and eGB. All cases showed retained nuclear ATRX and INI-1 . H3K27M or IDH1 mutation was seen in none. P53 mutation was more common in eGB, followed by PXAG3, and least common in PXAG2. BRAF V600E mutation was observed in 66.67% PXAG2, 33.33% PXAG3, and 50% eGB, with 100% concordance between immunohistochemistry (IHC) and sequencing. Thirty-six percent eGB, 33% PXAG3, and 61% PXAG2 harbored CDKN2A homozygous deletion. EGFR amplification was observed in 14% eGB and 66% of GB, IDH wt. PDL1 and CTLA-4 expression was higher in eGB (71.4% and 57.1%), PXAG3 (66.6% and100%), and PXAG2 (60% & 66.7%) as compared with GB, IDH wt (38.8% and 16.7%). Tumor-infiltrating lymphocytes were also observed in a majority of eGB and PXA (90% to 100%) in contrast to GB, IDH wt (66%). This analysis highlights the homogenous molecular and immune profile of eGB and PXA, suggesting the possibility that histologically and molecularly, these two entities represent 2 ends of a continuous spectrum with PXAG3 lying in between. Higher upregulation of PDL1, CTLA-4, and increased tumor infiltrating lymphocytes in these tumors as compared with GB, IDH wt suggests potential candidature for immunotherapy.

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.

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.

Gene expression based profiling of pleomorphic xanthoastrocytoma highlights two prognostic subgroups.

BACKGROUND: Pleomorphic xanthoastrocytomas (PXAs) are rare, accounting for less than 1% of astrocytomas, and commonly occur in young patients. The majority are WHO grade II. A fraction of tumors that present or recur with malignant change are classified as anaplastic (APXA, grade III). Limited data are available on their molecular characteristics. METHODOLOGY: Genome-wide expression profiling of 14 PXA and 6 APXAs was performed by microarray. Among differentially expressed genes (DEGs), Cyclin-Dependent Kinase 14 (CDK14) and Mitochondrial Fission Process 1 (MTFP1) were validated by qRT PCR. RESULT: Unsupervised hierarchical clustering revealed two distinct molecular clusters (Cluster 1: 10 PXA, 3 APXA and Cluster 2: 4 PXA, 3 APXA) with grade II and III tumors distributed in both highlighting molecular heterogeneity within the same grade. There was an insignificant difference in age, sex, immunohistochemical profile, frequency of BRAF mutation, or CDKN2A deletion among the two clusters. Significantly, worse progression-free survival was observed in cluster 2 (P=0.003). mRNA profiling-based prediction of recurrence was superior to and independent of histological grade, BRAF mutation, or CDKN2A deletion status. A total of 10 upregulated and 418 downregulated genes were identified between the PXA clusters. qRT-PCR validation of CDK14 (upregulated in cluster 2) and MTFP1 (upregulated in cluster 1) showed strong concordance with expression array data. CONCLUSION: This is the first comprehensive study highlighting distinct molecular subgroups of PXA. The differentially expressed genes between two clusters may potentially be used for developing histology independent classification schemes, prognostication and may serve as prospective therapeutic targets for PXA patients.

Is There Any Relationship Between Systemic Inflammatory Markers And Meningioma Grade?

Background: Systemic inflammatory markers have been found to be of value in predicting the prognosis in renal cell and gastrointestinal cancers. Recent studies in gliomas correlating with Systemic inflammatory markers (SIMS) have shown promise in predicting survival. Objective: Meningiomas are the commonest intracranial primary brain tumors in adults. There is a need to distinguish low and high grade meningiomas preoperatively as they have crucial implications for the radicality of surgical excision and prognostication. Methods: A retrospective search was conducted, and the newly diagnosed meningioma cases were studied. The preoperative hematological parameters of the patients and pathological tumor grades were noted. The grade 1 meningioma was defined as low-grade meningioma while grade 2 and 3 meningiomas were defined as high-grade meningioma. Statistical analysis was performed to determine the association between the hematological parameters and tumor grade. Results: Seven hundred and eighty meningioma cases with a mean age of 43.5 years were included. The ANC, NLR, and dNLR were found to be significantly elevated in high-grade meningioma (P = 0.03). Other inflammatory parameters including TLC failed to show a statistically significant difference when compared between the grades of meningioma. ROC analysis further showed limited value of these markers in predicting meningioma grade. However, an elevated ANC (OR = 1.08, 95% CI = 1.02-1.14), male sex (OR = 1.71, 95% CI = 1.13-2.58), and tumor origin from sites other than the skull base or thecal sac (OR = 3.33, 95% CI = 1.93-6.12) were predictive of high-grade meningioma in regression analysis. Conclusion: Preoperative hematological inflammatory parameters have limited value in predicting the grade of tumor in meningiomas. An elevated preoperative ANC, NLR, and dNLR were found to be more frequently associated with high grade of meningiomas.

Turning a New Chapter in Neurosurgery Outpatient Services: Telemedicine A "Savior" in this Pandemic.

BACKGROUND: Teleconsultation services in India, especially in neurosurgery, are relatively new. Despite its large-scale adoption during the COVID-19 pandemic, comprehensive analyses of patients' perspectives and hurdles are lacking. MATERIALS AND METHODS: We conducted an anonymized telephonic survey of consecutive neurosurgical patients who availed telemedicine services at our institute, using a validated, structured questionnaire. To prevent bias, interviewers were not involved in the study design/analyses. Patients' perception of usefulness and performance of teleconsultation was graded on a 5-point Likert scale. RESULTS: Of the 330 patients who availed teleconsultation services, 231 (70%) completed the survey. Even though 91% of the respondents had access to a smartphone, only 10% received a video-based teleconsult. As per respondents, the challenges included poor network (7%), suboptimal communication/discussion (5.6%), lack of physical examination (6%), and misinterpretation of prescription by pharmacists/patients (6%). The majority of the respondents (58%) either agreed/strongly agreed that teleconsultation helped them tide over the medical exigency during the lockdown; however, the clinical diagnosis did not influence this response (P = 0.21). The vast majority of the respondents felt that teleconsultation is beneficial (97%), as it minimizes their exposure to COVID-19. One-third of the patients preferred this service over physical visits and 60% agreed to its continuation till resumption of routine care. Access to video-teleconsultation was the chief suggestion in 39 of 74 suggestions received. CONCLUSIONS: Telemedicine in neurosurgery offers favorable patient satisfaction during this pandemic and may be a satisfactory alternative to physical outpatient services in the future. Video-based teleconsults should be the preferred modality of communication for neurosurgery patients.

Clinico-pathological and molecular characterization of diffuse midline gliomas: is there a prognostic significance?

PURPOSE: H3K27M mutant diffuse midline gliomas (DMGs) are considered grade IV irrespective of histological features and have dismal prognosis. We evaluated clinico-pathologic, radiological, and molecular characteristics of DMGs across all ages. METHODS: One twenty-six DMGs were identified over 10 years. Immunohistochemistry was done for H3K27M, ATRX, IDH1, and p53, and Sanger sequencing performed for IDH1 and H3K27M mutation. Patient demographics and clinico-radiologic characteristics were reviewed and survival analysis performed. RESULTS: DMGs comprised 5.3% of all gliomas with 49.2% H3K27M mutant and 50.8% wild types. Majority (75.68%) of pediatric and 38.20% of adults were H3K27M mutant (p = 0.0001). Amongst H3K27M mutants, brainstem (46.43%) was the commonest location in pediatric and thalamus (61.76%) in adults. H3K27M mutation was mutually exclusive with IDH mutation in 93.55%, while p53, ATRX mutation were seen in 56.4% and 30.6% cases respectively. Software-based immunohistochemistry evaluation (H-scoring) showed 99.2% concordance with sequencing for H3K27M mutation. Radiologically, no significant difference in contrast enhancement was seen between mutant and wild types (p = 0.05). The difference in overall survival (OS) was not significant in mutant versus wild types, with age or location. Tumor resection independently and on correlation with H3K27M did not influence OS (p = 0.51 and p = 0.47). Adjuvant therapy impacted survival significantly in adults (p = 0.0009), however, not in pediatric cases (p = 0.06). CONCLUSIONS: The study highlights the differences in frequency and location of pediatric and adult DMGs. IHC (H-scoring) for H3K27M mutation is an excellent surrogate for sequencing. Prognosis remains dismal irrespective of age, location, and H3K27M status. Potential therapeutic targets need to be explored.

Gamma Knife Radiosurgery: The Gold Standard Treatment for Intracranial Dural Arteriovenous Fistulas without Cortical Venous Drainage.

CONTEXT: Endovascular therapy is currently the most common treatment approach for intracranial dural arteriovenous fistula (DAVF), followed by microsurgery. Gamma Knife radiosurgery (GKS) is usually reserved as the last modality of treatment of intracranial DAVF. AIM: To evaluate the clinical and radiological outcome of GKS in the treatment of DAVF without CVD. SUBJECTS AND METHODS: This series includes patients who underwent GKS for intracranial DAVF without CVD over 10 years (Jan 2007 to Dec 2016) in All India Institute of Medical Sciences, New Delhi. Their demographic profile, clinical presentation, imaging details, GKS details, and follow-up clinical status were obtained retrospectively. Clinical follow-up, along with radiological assessment using MRI every 6 months was done after GKS. DSA was performed once MRI strongly suggested obliteration of DAVF. Patients who had a clinical follow-up of less than 1 year were excluded from the study. RESULTS: 5 patients (4 males and 1 female) who had DAVF without CVD were included the study. The mean age was 44.8 years. All patients had complete obliteration of fistula on digital subtraction angiography (DSA) at a mean duration of 24 months post GKS. All patients had complete resolution of symptoms at the last follow-up. CONCLUSIONS: Gamma Knife surgery is the most effective and the safest treatment modality for dealing with DAVFs without CVD. Instead of reserving it as the last resort for patients with DAVF without CVD, it should be considered as the gold standard treatment for DAVFs without CVD.

Neglected Traumatic Atlantoaxial Rotatory Dislocation in Adult: A Case Report.

Atlantoaxial rotatory dislocations (AARDs) are common in the pediatric population and rarely seen in adults. We describe a case of neglected AARD and subsequent management. A 25-year-old man developed a Fielding type 1 AARD following a road traffic accident. He was managed conservatively for 1.5 months before being referred to us. The patient underwent surgery 1.5 months after the accident. Closed reduction failed and C1-2 fixation with the Harms technique was performed after intraoperative reduction resulting in correction of deformity. Delay of treatment makes intraoperative reduction more difficult and increases the possibility of the chronic permanent change of neck muscles and ligaments. Hence, a high index of suspicion with a thorough clinical examination and judicious use of radiological investigations is paramount to the appropriate management of such cases.

Analysis of PD-L1 expression and T cell infiltration in different molecular subgroups of diffuse midline gliomas.

Diffuse midline gliomas (DMGs) are rare and devastating tumors with limited therapeutic options. Programmed death-ligand 1 (PD-L1) expression represents a potential predictive biomarker for immunotherapy. One hundred and twenty-six DMGs (89 adult and 37 pediatric) were assessed for immune profile (PD-L1, cluster of differentiation (CD3, CD8) and genetic markers (mutation in 27th amino acid of histone H3 (H3K27M), alpha thalassemia/mental retardation syndrome X-linked (ATRX), isocitrate dehydrogenase 1 (IDH1), p53) by immunohistochemistry. Sanger sequencing was done for IDH1 and H3K27M. The thalamus was the commonest site. Four molecular subgroups of DMGs were identified. H3K27M mutation was more frequent in children (P = 0.0001). The difference in median overall survival (OS) was not significant in any of the four molecular subgroups (P > 0.05). PD-L1 expression was significantly higher in H3K27M/IDH1 double-negative adult glioblastomas (GBMs) (P = 0.002). Strong PD-L1 expression was more frequent in grade IV tumors and thalamic location, although the difference was not significant (P = 0.14 and P = 0.19 respectively). Positive PD-L1 expression was significantly associated with high tumor-infiltrating lymphocytes count (P < 0.05). There was no significant difference in median OS in PD-L1-positive versus negative cases among four genetic subgroups (P > 0.05). On univariate analysis, there was no direct correlation of PD-L1 with any genetic alteration, except H3K27M mutation (P = 0.01). CD3 infiltration was similar in both adults and pediatric ages (84.3% and 78.4%, respectively) while CD8 expression was significantly greater in adults compared to children (74.1% vs 37.8%, P = 0.0001). This is the first comprehensive analysis highlighting molecular and immune profiles of DMGs. Despite molecular and clinicopathological diversity, overall survival in DMGs remains dismal. Multicentric studies with larger numbers of cases should be undertaken for stratifying DMGs according to their age, immune and molecular profiles, to develop effective immunotherapies.