Extended Unifrontal craniotomy for midline anterior cranial fossa meningiomas: A better shot at preservation of neurovascular structures.

Numerous surgical approaches have been described for the resection of anterior cranial fossa meningioma. The common problems associated with these approaches are excessive brain retraction, injury to neurovascular structures, transection of superior sagittal sinus (SSS), and a higher risk of new-onset anosmia. The authors describe a unilateral extended frontal approach with the aim to minimize brain handling without the need for SSS transection and possibly better olfaction preservation. METHODS: Thirteen patients with anterior cranial fossa meningioma were operated on using the novel technique of unilateral extended frontal skull base approach. The clinical presentation, radiological studies, intraoperative findings, and outcome at follow-up were recorded. RESULTS: Gross total tumor resection could be achieved in 12 out of 13 patients. At least one of the olfactory tracts could be anatomically preserved in all patients, and superior sagittal sinus was preserved in all patients. Functional olfaction preservation was achieved in 8 patients. No patient developed new-onset anosmia. CONCLUSIONS: The extended unilateral frontal approach is a viable and reliable alternative for extended bifrontal technique for the resection of large midline anterior cranial fossa meningiomas with avoidance of SSS ligation, decreased brain handling with better olfaction preservation while achieving comparable tumor resection and acceptable cosmetic outcomes.

Isolated embryonal rhabdomyosarcoma of the anterior petrous bone in a young child: Focusing on the intra-operative diagnosis and differentials.

OBJECTIVE: Rhabdomyosarcoma is a common soft tissue tumor, but isolated involvement of anterior portion of petrous bone is exceedingly rare. Here, we present a case of embryonal rhabdomyosarcoma involving the anterior petrous without involvement of the mastoid and middle ear. PATIENT: A 6-year-old boy presented with a progressive right side lower motor neuron facial paresis for 1-month duration along with headache and recurrent vomiting episodes. Radiology showed a contrast-enhancing lesion involving the right petrous apex. He underwent craniotomy and excision of the lesion. Based on the frozen section, a diagnosis of rhabdomyosarcoma was rendered, and gross total resection could be achieved. Postoperative course was uneventful. CONCLUSION: Isolated petrous bone involvement of embryonal rhabdomyosarcoma is a rare presentation. Intra-operative frozen section plays a key role in decision making regarding the extent of excision. Hence, a prompt and accurate diagnosis is essential in managing these cases.

Suprasellar masquerader: Chordoid glioma.

BACKGROUND: Chordoid glioma is a rare well-circumscribed glial neoplasm arising in adults and predominantly affects females. Tanycytes of the third ventricle have been proposed as the cell of origin owing to its location. It is characterized by chordoid features with myxoid and inflammatory stroma and recurrent PRKCA p.D463H missense mutation. CASE REPORT: We present two cases (30-year-old female and 45-year-old male) with similar complaints of behavioral change and headache. Midline suprasellar homogeneously enhancing mass was seen on contrast-enhanced magnetic resonance imaging. Histopathology and immunohistochemistry was characteristic of chordoid glioma with cords and clusters of epithelioid cells arranged in a solid pattern. There were variable amounts of myxoid stroma and lymphoplasmacytic infiltrate. No mitosis, necrosis, or brain invasion was noted. The cells expressed strong diffuse positivity for glial fibrillary acid protein (GFAP) and weak nuclear thyroid transcription factor (TTF-1). Epithelial membrane antigen (EMA)and brachyury were negative. Subsequently, the lady underwent gross total excision and died soon after the operation. The male patient received radiotherapy and is currently doing well after 6 months of follow-up. CONCLUSION: The rare occurrence as well as the radiological and morphological overlaps in chordoid gliomas make them a true masquerader. Combination of GFAP and TTF-1 in the immunohistochemical panel can be useful in differential diagnosis. Mainstay of treatment is complete surgical excision, with adjuvant radiotherapy becoming increasingly important.

Immunohistochemical Surrogates for Molecular Stratification in Medulloblastoma.

BACKGROUND: The WHO classification of central nervous system neoplasms (2016) recognized 4 histologic variants and genetically defined molecular subgroups within medulloblastoma (MB). Further, in the 2021 classification, new subtypes have been provisionally added within the existing subgroups reflecting the biological diversity. YAP1, GAB1, and ß-catenin were conventionally accepted as surrogate markers to identify these genetic subgroups. OBJECTIVES: We aimed to stratify MB into molecular subgroups using 3 immunohistochemical markers. TP53 mutation was also assessed in Wingless (WNT), and Sonic Hedgehog (SHH) subgroups. Demographic profiles, imaging details, and survival outcomes were compared within these molecular subgroups. PATIENTS AND METHODS: Our cohort included 164 MB cases diagnosed over the last 10 years. The histologic variants were identified on histology, and tumors were molecularly stratified using YAP1, GAB1, and ß-catenin. Further, TP53 mutation was assessed using immunohistochemical in WNT and SHH subgroups. The clinical details and survival outcomes were retrieved from the records, and the mentioned correlates were evaluated statistically. RESULTS: The age ranged from 1 to 52 years with M:F ratio of 2:1. Group 3/group 4 constituted the majority (48.4%), followed by SHH (45.9%) and WNT subgroups (5.7%). Desmoplastic/nodular and MB with extensive nodularity had the best survival, whereas large cell/anaplastic had the worst. The follow-up period ranged from 1 to 129 months. The best outcome was observed for the WNT subgroup, followed by the SHH subgroup; group 3/group 4 had the worst. Among the SHH subgroup, TP53 mutant tumors had a significantly poorer outcome compared with SHH-TP53 wildtype. CONCLUSIONS: Molecular stratification significantly contributes to prognostication, and a panel of 3 antibodies is helpful in stratifying MB into its subgroups in centers where access to advanced molecular testing is limited. Our study reinforces the efficacy of incorporating this cost-effective, minimal panel into routine practice for stratification. Further, we propose a 3-risk stratification grouping, incorporating morphology and molecular markers.

Deceptive Appearances - Spastic Paretic Hemifacial Contractures in Cases of Seventh Nerve Involvement 'Inside' and 'Outside' the Brainstem.

Spastic paretic hemifacial contracture (SPHC) is a rare clinical phenomenon characterized by facial weakness and simultaneous well-sustained contraction of the unilateral half of the face, mimicking a paresis of the normal contralateral side on casual inspection. We present three cases with such phenomenon and have postulated the underlying mechanisms. One patient had intrinsic brainstem glioma, and the others were operated for extra-axial lesions compressing the pons. The former presented with SPHC, whereas the latter two gradually developed this phenomenon following postoperative facial paresis. This condition is possibly due to denervation hyper-excitability of the facial supranuclear pathway or an aberrant regeneration secondary to nerve injury leading to functional facial-nerve nuclear reorganization. SPHC occurrence is not limited to intra-axial lesions but can also be seen after partial injury to the facial nerve beyond its exit from the brainstem.

Controlled arachnoid opening to aid endoscopic trans-sphenoidal extrarachnoidal dissection of pituitary macroadenoma.

OBJECTIVES: The arachnoid often bulges prematurely during surgical excision of large pituitary tumors obscuring the deeper regions and crevices preventing total excision. Pushing the arachnoid may not be helpful and may tear it inadvertently and extensively leading to complications. We have described controlled arachnoid opening in large pituitary macroadenomas during the final stages of excision to gain access to the hidden portions and compared our results to the conventional technique. PATIENTS AND METHODS: Patients with pituitary macroadenoma of Hardy's III and KNOSP II in whom arachnoid had bulged prematurely were considered for study. They were grouped temporally. In first group (n = 12), the arachnoid was pushed to retrieve the tumor and in the second group (n = 10) it was punctured to aid resection. The extent of resection was assessed on postoperative scans, and complications in both groups, were noted. RESULTS: In the first group where arachnoid was pushed to retrieve tumor, Gross Total Resection (GTR) could be achieved in 5 patients. Inadvertent large arachnoid tear occurred in 3 patients of which, 2 developed CSF Rhinorrhoea. No patient had neurovascular injury.In the second group, GTR could be achieved in all without any added complications. CONCLUSION: Deliberate needle puncture and controlled drainage of CSF from arachnoid that bulges prematurely while endoscopic Transsphenoidal surgery for large pituitary tumors is a safe and effective method to gain access to the hidden portions of tumor to achieve GTR.

Delayed yet effective response of an endolymphatic sac tumor to radiosurgery: case report focusing on its radio-biological behavior.

Endolymphatic sac tumors (ELST), though benign are locally invasive lesions. Owing to its vascularity, complete surgical resection is often not possible and adjuvant gamma knife radiosurgery (GKRS) is advocated to control tumor growth. These lesions do not uniformly respond to radiation therapy in the initial phase and their early radiobiological course after GKRS is less understood. We discuss a case of residual ELST where a mild increase was noted at 36 months following GKRS and then regressed completely after a decade. This report possibly has the longest follow-up revealing the true efficacy of GKRS in these tumors. ELST shows a variable response in the early years after GKRS. They may remain static, regress or increase in size. One should be aware of these patterns of early radiological responses and a long term follow up is warranted as some lesions may show radiosurgical effectiveness after a long latent period.

A Randomized Study of Short Course (One Week) Radiation Therapy with or without Temozolomide in Elderly and/or Frail Patients with Newly Diagnosed Glioblastoma (GBM).

OBJECTIVE: Short-course radiotherapy (25 Gy in 5 fractions) has been shown to be non-inferior to standard course radiotherapy in elderly and frail patients (60 Gy in 30 fractions). The purpose of this study was to determine the effects of temozolomide combined with short-course radiotherapy on the outcome of elderly and frail patients. METHODS: Between January 2017 and November 2018, 90 patients (65 years old and KPS score of 50-70; 65 years old and KPS score of 80-100; and 65 years old and KPS score of 50-70) were assessed for eligibility. Nine patients were excluded because they did not meet the inclusion criteria, six patients declined to participate, and four patients were unable to complete the quality-of-life questionnaire. The remaining 71 patients were divided into two arms at random in a 1:1 ratio. Short-course radiotherapy with concurrent temozolomide and adjuvant temozolomide was given to Arm 1, while short-course radiotherapy alone was given to Arm 2. RESULTS: In terms of overall survival and progression-free survival, radiotherapy with concurrent temozolomide and adjuvant temozolomide outperformed short-course radiotherapy alone. The median overall survival in arm 1 was 146 days and 121 days in arm 2 (P=0.146). The median progression-free survival in arm 1 was 109.50 days, while it was 77 days in arm 2 (P=0.028). With a median follow-up time of 6 months, the quality of life at 4 weeks and 12 weeks after treatment was not different between the two arms. CONCLUSION: We concluded that adding temozolomide to short-course radiotherapy significantly improved progression-free survival and showed an increasing trend in overall survival without compromising the quality of life.

Surgical Outcome Analysis of Large and Giant Petroclival Meningiomas with Special Reference to Quality of Life Issues.

Background: Management strategies for petroclival menigiomas remain controversial. Objectives: We share our experience in management of large and giant true petroclival meniongiomas with special emphasis on patient reported quality of life parameters. Methods: This is a single center study of 47 patients between 2008 and 2018. All patients were checked for tumor specific parameters, clinical parameters, extent of surgical excision, and outcome, as assessed by Karnofsky performance score (KPS), Glasgow outcome score, clinical status, and by SF-36 questionnaire. Results: 32/47 patients' data were assessed. Symptoms included headache (62.5%), involvement of 5th nerve (47%), facial nerve (40.6%), lower cranial nerves (37.5%), cerebellar signs (84%), and long tract signs in (50%) of patients. The mean preoperative KPS was 83.75+/-6.59. Surgical approaches included retromastoid suboccipital craniotomy (50%), Kawase's approach (31.25%), and others in 18.25% patients. 40.625% (n = 13) had a gross total excision, near total resection (NTR) was achieved in 53.125% (n = 17), and 6.25% (n = 2) had a subtotal excision (STE). In 13 patients who had gross total resection (GTR), there were 12 (70.5%) new neurological deficits, while among the 19 patients with NTR, only 5 (29.5%) new neurological deficits were seen. No new onset neurological deficit was seen in patients with STE of tumor. Patient assessed QoL parameters were worse in patients with GTR and best in patients with NTR/STE + GKRS. Conclusion: In patients of large/giant petroclival meningiomas, NTE/STE with adjuvant GKRS provided better preservation of quality of life.

IgG4-related Pachymeningitis as a Cause of Spinal Epidural Compression: Can Intraoperative Frozen Sections Predict the Underlying Pathology?

At times, spinal lesions are part of systemic manifestations of autoimmune disease. Awareness regarding their clinicopathological spectrum, particularly the lesions which usually respond to steroids/immunotherapy, is essential to avoid unwanted surgical morbidity. We discuss a case of a young-man presenting with thoracic spinal epidural compressive lesion which was indeed a manifestation of IgG4-related hypertrophic pachymeningitis. The mass was firmly adherent to the dura and extended into left neural foramen/paravertebral space which precluded complete excision. Frozen sections suggested fibro-inflammatory stroma with large areas of fibrosis and lymphoplasmacytic infiltrate. After subtotal excision, the patient improved with medical therapy at 1-year follow-up. Although uncommon, the case highlights the need to consider spinal presentation of this rare entity, especially in the context of autoimmune disorders or even in isolation. In this regard, intraoperative frozen section can hint the underlying inflammatory/autoimmune pathology, guide further course of surgery as well as limit unwarranted operative morbidity.

Revisiting Surgery in the Current Era of Gamma Knife for Cavernous Sinus Lesions.

Background: The challenges associated with surgeries of cavernous sinus (CS) lesions have shifted the management trend towards upfront gamma knife radiosurgery (GKRS). Although GKRS is effective in arresting the progression of certain small residual/recurrent lesions, its efficacy in alleviating neurological deficits is less evident. Furthermore, GKRS without establishing the histopathological diagnosis, at times can be detrimental. Objective: We present our clinical experience to reemphasize the role of surgery for CS lesions in the current era of upfront GKRS. Materials and Methods: We reviewed our database of 32 patients with various CS lesions treated by surgery for progressive cranial nerve deficits. The follow-up data were analyzed for the extent of resection, and in particular for improvement in their symptoms. Results: The lesions were confirmed as hemangioma (CSH)-8, meningioma-8, trigeminal schwannoma-6, chordoma-3, residual pituitary with CS extension-3, fungal granuloma-3, and dysgerminoma-1. Symptoms improved in 23 (complete in 13) and remained at least static in six patients. Follow-up ranged from 4-36 months. Conclusions: The nature of pathology should determine the management modality in CS lesions. Excision of CS schwannomas and chordomas yields rapid clinical improvement and good long-term outcomes. Resection is preferred for large CSH and functioning pituitary tumors. Although the clinical improvement may be less dramatic, surgery debulks the meningiomas. Most importantly, surgery also establishes the histopathological diagnosis of CS lesions. Even with an easy alternative of upfront GKRS, resection has a definite role in the primary management of most CS pathologies.

Molecular subgrouping of ependymoma across three anatomic sites and their prognostic implications.

The 2021 WHO classification stratifies ependymoma (EPN) into nine molecular subgroups according to the anatomic locations which outperforms histological grading. We aimed at molecularly reclassifying 200 EPN using immunohistochemistry (IHC) and sequencing for ZFTA fusions in supratentorial (ST) EPN. Further, we assessed the utility of L1CAM, cyclinD1, and p65 markers in identifying ZFTA fusion. Demographic profiles, histologic features, molecular subgroups and clinical outcome were retrospectively analyzed. IHC for L1CAM, cyclinD1, p65, H3K27me3, and H3K27M and sequencing for ZFTA fusion were performed. ZFTA fusions were identified in 44.8% ST EPN. p65 displayed the highest specificity (93.8%), while L1CAM had the highest sensitivity (92.3%) in detecting ZFTA fusions. The negative predictive value approached 96.6% and sensitivity improved to 96.2% with combinatorial IHC (L1CAM, cyclinD1, p65). H3K27me3 loss (PF-A) was noted in 65% PF EPN. Our results provide evidence that a combination of two of three (L1CAM, p65, and cyclinD1) can be used as surrogate markers for predicting fusion. ZFTA fusion, and its surrogate markers in ST, and H3K27me3 and younger age (< 5 years) in PF showed significant correlation with PFS and OS on univariate and Kaplan-Meier analysis. On multivariate analysis, H3K27me3 loss and younger age group are associated with poor clinical outcome.

Cerebral phaeohyphomycosis: The 'Dark Side' of fungal infections.

PURPOSE: Cerebral phaeohyphomycosis is a rare and fatal fungal infection of the central nervous system (CNS) caused by dematiaceous fungi. The aim of this study was to analyse the clinico- radiological presentation, pathology and outcome of cerebral phaeohyphomycosis and discuss the relevant literature. PATIENTS AND METHODS: Data of 7 patients diagnosed with cerebral phaeohyphomycosis and managed at our institute between 2014 and 2020 was collected and reviewed retrospectively. The diagnosis was established after surgery on KOH mount, Sabouraud dextrose agar, frozen section or histopathology. The clinical, radiological and pathological characteristics along with outcomes were analysed. RESULTS: Three patients with underlying comorbidities [chronic renal failure-2 and haematological malignancy -1] presented with brain abscess. The remaining 4 had no comorbidities. Two of them mimicked cystic glioma and one patient presented as intraventricular tumour. Another patient on anti- tubercular treatment for suspected pulmonary tuberculosis presented with encephalitis. Histopathology in all patients showed diffuse micro abscesses with coarse and reactive gliosis in the adjacent brain parenchyma and chronic lymphomononuclear inflammation without angioinvasion or vasculitis. Four showed granuloma formation. Antifungals were started after diagnosis. Six out of seven patients died and one was lost to follow up. CONCLUSION: Cerebral phaeohyphomycosis presents as abscesses in immunocompromised patients and mimics tumours in immunocompetent patients. KOH mount and frozen section examination is simple yet effective tool for establishing early diagnosis. Overall, the prognosis is dismal. Administering antifungals early in the course of management along with aggressive surgical excision may improve outcomes.

Temozolomide Nonresponsiveness in Aggressive Prolactinomas and Carcinomas: Management and Outcomes.

CONTEXT: Temozolomide (TMZ) is endorsed as the treatment of choice in aggressive or malignant pituitary adenomas. OBJECTIVE: Herein we describe a case of an aggressive prolactinoma that was resistant to TMZ. We performed a literature review of similar nonresponsive, aggressive prolactinomas. METHODS: A 40-year-old woman presented with a giant prolactinoma that required cabergoline, transsphenoidal surgery, and radiotherapy to achieve near-normal prolactin and apparently no residual tumor. A year later, she presented with multiple cranial nerve involvement due to a recurrent tumor extending to the infratemporal fossa. She underwent transfrontal surgery, second radiotherapy, and was started on TMZ. Despite 8 cycles of temozolomide (200 mg/m2, 5/28-day cycle), she had progressive disease and ultimately succumbed to the disease. PubMed/MEDLINE, Google Scholar, and prior review articles were searched for manuscripts about patients with aggressive prolactinomas who had been treated with TMZ. Data on demography, duration of therapy, and management outcomes were analyzed in those with progressive disease. RESULTS: We identified 94 cases of patients with aggressive/malignant prolactinomas in the literature who had received TMZ. Progressive disease despite TMZ was present in 36 cases (38%). There was a male preponderance (65%) among these and 40% had aggressive prolactinomas, whereas the rest had carcinomas. Patients received a median of 8 cycles (interquartile range, 3.5-11.5) of TMZ. O6-methylguanine-DNA-methyltransferase (MGMT) immunostaining was negative in 35%. Overall mortality at the time of publication was 40%, at a duration varying from 2 to 20 years from diagnosis. CONCLUSION: TMZ resistance in aggressive/malignant prolactinomas is challenging. Progressive disease on optimal TMZ treatment entails the use of newer agents.

Extra-axial, dural-based atypical teratoid/rhabdoid tumor.

Atypical teratoid/rhabdoid tumors (ATRTs) are malignant central nervous system tumors that affect early childhood (< 3 years), and mostly located in the infratentorial space. Owing to an infrequent occurrence, their radiological features have not been completely defined. Nevertheless, these are characteristically intra-axial except for few instances in the cerebellopontine angle region. We describe a case of a 10-year-old boy who harbored an extra-axial, dural-based ATRT in the right parietal region. The lesion was totally excised followed by adjuvant chemo-radiotherapy. At 10-month follow-up, he was well with no recurrence. The report intends to highlight an atypical imaging presentation of ATRT in an older child, and adds to the radiological spectrum. This uncommon pathology should be borne in mind, even in a supratentorial dural-based location.

Primary Spinal Intradural Ewing's Sarcoma: Hemorrhagic Presentation with Acute Neurological Deterioration in Two Pediatric Patients.

Extraosseous primary spinal intradural Ewing's sarcoma (ES) is an unusual entity. Bleed within such tumors with acute neurological worsening is extremely rare, especially in the pediatric age. In this article, we present two children with intradural-extramedullary ES who had sudden decline in their neurological status consequent to an intratumoral hemorrhage. We discuss their clinical course and also briefly review the pertinent literature. Spinal intradural Ewing's sarcomas possibly have a tendency to bleed. A short clinical symptomatology along with an acute neurological deterioration and radiologic evidence of intratumoral hemorrhage in a spinal intradural tumor should raise the suspicion of an ES.

Revisiting Intraoperative 2D USG with Saline-Air Mixture as Contrast for Resection of Eloquent Area Glioma in Resource-Deficient Countries.

Background Advanced ultrasound, intraoperative magnetic resonance imaging (MRI), neuromonitoring, and aminolevulenic acid have improved the resection and safety of eloquent area gliomas. However, availability of these modern gadgets is a major concern in resource-deficient countries. A two-dimensional ultrasonography 2D USG is cheaper, provides real-time imaging, and is already established but underutilized instrument. Objective Here, we revisited the principles of 2D USG and used it for eloquent-area glioma surgery. Materials and Methods Fifty-eight patients with eloquent area gliomas were operated in last 2 years with the aid of 2D USG with 6-13 MHz curvilinear probe. Preoperative diagnosis was high-grade glioma in 38 and low-grade glioma (LGG) in 20 patients. Tumors were categorized as predominantly hyperechoic (27), uniformly hyperechoic (7), mixed echogenicity (21), and cystic (3). Results Intraoperatively, 2D USG could define the tumor margins in 46 cases. Of these, USG suggested gross total excision in 38 patients and subtotal in 8 patients. The findings matched with follow-up MRI in 34 patients who showed hyperechogenicity (predominant/uniform). Injecting saline with air in to the resection cavity and insinuating through adjacent brain parenchyma helped in detecting residual lesion in three cystic gliomas and in two LGG where the tumor cavity collapsed. Conclusion 2D USG is a helpful tool in eloquent area glioma surgery, especially in resource-limited countries. Visualization through adjacent parenchyma and injection of saline-air mixture in to the resection cavity helped in delineating residual lesion. Extent of resection is best monitored by 2D USG when tumor appeared hyperechoic (predominant/uniform).