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Postoperative fever is mostly transient and inconsequential but may portend a serious postoperative infection requiring a thorough evaluation, especially during the recent COVID-19 pandemic. We aimed to determine the incidence, causes and outcomes of postoperative fever in neurosurgical patients, as well as to evaluate a protocol for management of postoperative fever. We conducted a prospective study over 12 months, recruiting 425 adult patients operated for non-traumatic neurosurgical indications. We followed a standard protocol for the evaluation and management of postoperative fever collecting data regarding operative details, daily maximal temperature, clinical features, as well as use of surgical drains, urinary catheters, and other invasive adjuncts. Elevated body temperature of 99.9°F or 37.7 °C for over 48 h or associated with clinical deterioration or localising features was considered as "fever" and was evaluated according to our protocol. We classified elevated temperature not meeting this criterion as a transient elevation in temperature (TET). Sixty-five patients (13.5%) had postoperative fever. Transient elevation of temperature, occurring in 40 patients (8.8%) was most common in the first 48 h after surgery. The most common causes of fever were urinary tract infections (13.7%), followed by aseptic meningitis (10.8%), wound infections and pneumonia. Various aetiologies of fever followed distinct patterns, with COVID-19 and meningitis causing high-grade, prolonged fever. Multivariate analysis revealed cranial surgery, prolonged duration of surgery, urinary catheters and wound drains retained beyond POD 3 to predict fever. Postoperative fever was associated with significantly longer duration of hospital admission. COVID-19 had a high mortality rate in the early postoperative period.

Incomplete surgical removal of craniopharyngiomas frequently results in suboptimal oncological control. Radiation therapy is usually offered in these cases to prevent local recurrence of disease; however, the efficacy of radiation is limited by its potential adverse effect, particularly in younger patients. This study was undertaken to compare long-term outcomes and rates of postoperative obesity and endocrinopathy in patients undergoing either upfront adjuvant radiation after surgery, or postoperative surveillance with progression-contingent intervention.Thirty-seven patients aged25 years who had undergone primary incomplete surgical resection of craniopharyngiomas were retrospectively identified and categorized according to the prescribed treatment strategy. Recurrence rates, functional status, neuro-ophthalmologic, and endocrine outcomes were studied in both groups of patients.Twenty-three patients received upfront adjuvant radiation, and 14 patients underwent postoperative surveillance. Adjuvant radiation in the former group was delivered using either conventional (n=10), 3D-conformal (n=4), or fractionated stereotactic (n=9) techniques using a linear accelerator. The mean follow-up duration was 64.7 months (range 14-134 months). Disease progression was significantly higher in patients undergoing surveillance as compared to those undergoing upfront adjuvant radiation (71.4 versus 17.4%; p=0.002). Median progression-free survival times were 129 months and 27 months in the upfront adjuvant radiation and surveillance groups, respectively (p=0.007). In patients undergoing surveillance, 50% ultimately required irradiation, and the median radiation-free survival time in this subgroup was 57 months. Two children in the adjuvant radiation group developed asymptomatic radiation-related vasculopathies on follow-up; however, there were no statistically significant differences between the two groups in terms of visual, functional, or pituitary-hypothalamic function at last follow-up.In comparison to upfront adjuvant radiation following incomplete craniopharyngioma resection significantly, a strategy of postoperative surveillance resulted in less durable disease control but allowed radiation therapy to be delayed by a median time of 57 months, without significant detriment to global functional, visual, and neuro-endocrinological outcomes. The merits and demerits of either strategy should be carefully considered in the post-surgical management of these patients.

There is limited literature on outcomes after surgical treatment of giant craniopharyngiomas in adult and pediatric patients.A retrospective review of 159 patients undergoing surgery for craniopharyngiomas at a single institution was performed. Patients with giant craniopharyngiomas (maximum dimension ≥4.5 cm) were compared with nongiant tumors in terms of various clinical and radiological parameters and long-term surgical outcomes. Extent of resection was determined by postoperative magnetic resonance imaging. Factors associated with post-treatment obesity were also analyzed.Giant craniopharyngiomas (n = 66) were characterized by higher rates of childhood presentation, visual impairment, neurological deficits, multicompartmental involvement, and hydrocephalus as compared with nongiant tumors (n = 139). Giant tumors also were less likely to undergo transsphenoidal resection and were associated with a higher rate of postoperative neurological morbidity. There were no significant differences between the 2 groups in terms of extent of resection, use of postoperative radiation therapy, and long-term endocrinological outcomes. Overall recurrence rates over a mean follow-up period of 4.1 years were similar between giant and nongiant tumors; however, recurrences after presumed gross total resection/near total resection were significantly higher in the former subgroup versus the latter (39.4% vs. 18.4%; P = 0.044). Risk factors for post-treatment obesity in giant craniopharyngiomas included adult age (P = 0.001), preoperative obesity (P = 0.003), and hypothalamic involvement (P = 0.012).Gross total resection/near total resection of giant craniopharyngiomas can be achieved at rates comparable to nongiant tumors. However, there remains a greater risk of postoperative neurological morbidity. Radiation therapy mitigates the risk of recurrence on long-term follow-up.

Objective Acromegaly is a syndrome of metabolic alterations secondary to increased growth hormone levels from a somatotroph pituitary adenoma. A multidisciplinary approach beginning with surgery, followed by adjuvant radiation or medical therapy for residual disease, is considered standard of care. Several factors affect the likelihood of remission after surgery, but the impact of surgical experience on remission rates has not been adequately assessed. Methods Retrospective review of 203 patients, divided into 2 eras (era 1, 102 patients; era 2, 101 patients) of patients who underwent transsphenoidal surgery for acromegaly by a single surgeon over 11 years, was performed, determining the effect of surgical experience on rates of remission and various complications. Remission was defined according to the 2014 Endocrine Society Clinical Practice Guideline. Results The rate of surgical remission was 40.6% (62.9% among noninvasive adenomas). Rates of surgical remission significantly improved in the latter half of this cohort (31.2% in the first half vs. 50% in the second half), despite other factors being comparable. On multivariate analysis, surgeon experience, cavernous sinus invasion, and preoperative growth hormone levels affected the rates of surgical remission. Rates of cerebrospinal fluid leak and hypopituitarism were lower in the second half, whereas resolution of acromegaly-associated comorbidities was increased. Conclusions We report, in this large single-surgeon review of endoscopically operated acromegaly cases, increased rates of surgical remission and reduced complications with increasing surgeon experience. The overall experience of the treating team in dealing with perioperative and intraoperative factors also contributes to improved outcomes.

Introduction: Gliomas were previously classified histologically, although now the latest WHO classification incorporates several molecular markers to classify these. Detection of TERT promoter mutations is assuming increased importance due to its relevance to prognostication.: The aim of this study was to determine the frequency of TERT promoter mutations, association of TERT promoter mutations with other molecular alterations and to assess the role of TERT promoter mutations in overall survival and progression-free survival in relation to histological and molecular glioma subtypes.This study analyzed a cohort of 107 adult patients with diffuse gliomas, WHO grades II and III and glioblastoma, by immunohistochemistry for IDH and ATRX mutations, FISH for 1p/19q co-deletions and PCR sequencing for TERT promoter mutation. Further, five glioma molecular sub-groups were derived using three molecular alteration and included the sub-groups with: i) IDH mutations only, ii) IDH and TERT mutations only, iii) IDH and 1p/19q co-deletion only, iv) Triple negative, and v) Triple positive.IDH mutations and 1p/19q co-deletions were individually and significantly associated with an improved progression free (P = 0.001 and P = 0.002, respectively) and overall survival (P = 0.000 and P = 0.005, respectively) in the present cohort of gliomas. TERT promoter mutations occurred frequently in anaplastic oligodendrogliomas (94%), oligodendrogliomas (87.5%) and glioblastomas (54%). Sub-division into molecular sub-groups showed that the triple-positive tumors carried the best prognosis, followed by IDH only, triple negative and finally the TERT mutation only tumors (P0.000).: This indicates that sub-classification using these molecular markers separates tumors into prognostically relevant categories.

Silent corticotroph adenomas (SCAs) are a rare subtype of non-functional pituitary adenoma. While it has been suggested that they are more aggressive and recur more frequently following excision, there is limited literature on the optimum treatment strategy for these tumors, especially regarding the role of radiation therapy in incompletely resected tumors. We assimilated data from 62 SCAs and 238 other non-functional adenomas (ONAs), defined according to the WHO 2017 criteria that incorporates transcription factor analysis. We compared their clinicoradiological characteristics, such as hormonal levels, tumor configuration, size, and invasiveness. For 52 SCAs and 205 ONAs with serial follow-up imaging, we studied outcomes for progression after subtotal resection with or without radiation therapy or recurrence after gross total resection. Kaplan Meier analysis for recurrence or progression was used to determine the need for a differential treatment strategy for SCAs compared with other non-functional adenomas specifically concerning the role of radiotherapy. Patients with SCAs present at a younger age than ONAs (43.9 years vs. 48.2 years, p = 0.014), with larger (14.9 cc vs. 9.7 cc, p = 0.006) and more invasive adenomas (61.2% vs. 45.8%, p = 0.021). Overall, SCAs are more likely to recur or progress (48.7 vs. 15.7%, p

PURPOSE: During the ongoing COVID-19 pandemic, endonasal surgeries for sellar-suprasellar lesions were discouraged due to the risk of transmission of the disease. We reviewed the changes in our management protocol for these lesions as our disease understanding and preparedness evolved. MATERIALS AND METHODS: This was a retrospective observational study including patients with sellar-suprasellar and clival lesions presenting to us between March and October 2020. Management protocols were divided into three phases based on the prevalence of the disease and the number of mandatory preoperative COVID-19 tests being conducted. The surgical approach used was analyzed in relation to the preferred approach during pre-COVID times, and surgical outcomes and complications were noted. RESULTS: A total of 31 cases were operated during this period. During Phase I (low prevalence; no preoperative COVID testing) endonasal surgeries were largely abandoned in favor of transcranial approaches. In Phase II (medium prevalence; one preoperative COVID test) we gradually resumed endonasal surgeries for 'emergent' and 'essential' cases, and subsequently in Phase III (high prevalence; two preoperative COVID tests), we had no hesitation in performing 'elective' endonasal surgeries with additional barriers for prevention of aerosol transmission. No patient developed COVID-19 infection postoperatively. Eight HCWs in our department acquired the disease during this period, none of whom were directly involved in the surgeries for the above cohort of patients. CONCLUSIONS: With a strict preoperative COVID testing protocol, adherence to proper drilling techniques and using additional barriers to prevent droplet and aerosol spread, endonasal surgeries for sellar-suprasellar lesions are safe during this COVID-19 pandemic.

Multiple Endocrine Neoplasia type-1 (MEN1) is an autosomal dominant disorder with a combined occurrence of tumours of parathyroid glands, pancreatic islets, and anterior pituitary. About 90% of these patients carry mutations in the MEN1 gene, though the spectrum is not well defined in India. Forty clinically suspected cases of MEN1 were enrolled prospectively over six years; 32 patients (23 index-cases and nine affected relatives) with≥2 classical endocrine tumours of MEN1 were considered definite, and eight were categorised as ‘MEN1-like’. Details of their clinical presentation, treatment and mutational analysis including MEN1 gene, 3′ and 5′ untranslated regions (UTR) of MEN1, CDKN1B, and CaSR genes were collated. Asymptomatic first-degree relatives were also screened. Among the 32 definite MEN1 patients, all had primary hyperparathyroidism, 22 (68.7%) had gastroentero-pancreatic neuroendocrine tumours, and 21 (66%) had pituitary adenoma. Of the 23 definite index-cases, 13 (56.5%) carried mutations in the MEN1 gene. Five of nine affected first-degree relatives (55.5%), and four of 10 asymptomatic relatives (40%) also had MEN1 mutations. Seven of 10 MEN1 mutation-negative definite index-cases harboured p.V109G polymorphism in the CDKN1B gene. All eight MEN1-like cases were negative for mutations and large deletions in MEN1, mutations in 3′ and 5′ UTR of MEN1, CaSR and CDKN1B genes. The study has helped to clearly document the pattern of mutations among Indian MEN1 patients. However, the absence of MEN1 mutation in ~44% of cases and the presence of p.V109G polymorphism in CDKN1B gene raise the question whether such polymorphisms could independently contribute to pathogenesis.

There is no consensus regarding the use of perioperative steroids for transsphenoidal pituitary surgery. We audited the effectiveness and safety of our selective perioperative steroid supplementation protocol in patients with pituitary adenomas. Two hundred ninety-seven patients underwent 306 endoscopic transsphenoidal surgeries for removal of their pituitary tumors. Steroids were given to those with an impaired hypothalamic-pituitary-adrenal (HPA) axis, age ≥ 60 years, clinical apoplexy, hyponatremia, or if the pituitary gland was not preserved at surgery. We excluded 111 patients in whom the integrity of the HPA axis could not be determined. We compared the incidence of early postoperative adrenal insufficiency and complications in 135 patients with intact HPA axes who underwent surgery without steroids (group A) with 60 patients who had compromised preoperative HPA axes and received perioperative steroids (group B). In addition, we audited the total number of protocol violations during this period. Five patients (3.7%) in group A developed postoperative hypocortisolemia. There was no significant difference in the incidence of cerebrospinal fluid leak, diabetes insipidus, or hyponatremia between both groups. There were protocol deviations in 47 (15.4%) patients. Twenty one of these patients did not receive perioperative steroids in violation of the protocol, of whom 4 (19%) developed postoperative hypocortisolemia. Our steroid sparing protocol was both safe and effective. The 15% incidence of protocol deviations is a reminder that the rigorous usage of checklists is mandatory for successful clinical practice.

Supratentorial ependymomas (STEs) are an aggressive group of ependymomas, topographically distinct from their posterior fossa and spinal counterparts. Zinc finger translocation associated (ZFTA) fusion-positive cases have been reported to account for the majority of STEs, although data on its association with poorer outcomes are inconsistent.We assessed the prevalence of the ZFTA fusion by reverse-transcription polymerase chain reaction and fluorescence in situ hybridization in a cohort of 61 patients (68 samples) with STE. Our primary outcome was to determine the role of the ZFTA fusion on progression-free and overall survival of patients with STE. Our secondary objectives were to assess the impact of ZFTA fusion on nuclear factor (NF)-kB pathway signaling via surrogate markers of this pathway, namely COX-2, CCND1, and L1 cell adhesion molecule.ZFTA fusion was noted in 21.3% of STEs in our cohort. The presence of this rearrangement did not significantly impact the progression-free or overall survival of patients with STEs and was not associated with upregulation of markers of the NF-kB pathway. Only gross total resection was significantly associated with better progression-free survival.In contradiction to previous reports from across the world, the ZFTA fusion is far less prevalent among our population. It does not appear to drive NF-kB signaling or significantly affect outcomes. Gross total resection must be attempted in all cases of STE and adjuvant radiation and/or chemotherapy employed when gross total resection is not achieved.

Background The optimal management of clinoidal meningiomas (CMs) continues to be debated. Methods We constituted a task force comprising the members of the EANS skull base committee along with international experts to derive recommendations for the management of these tumors. The data from the literature along with contemporary practice patterns were discussed within the task force to generate consensual recommendations. Results and conclusion This article represents the consensus opinion of the task force regarding pre-operative evaluations, patient’s counselling, surgical classification, and optimal surgical strategy. Although this analysis yielded only Class B evidence and expert opinions, it should guide practitioners in the management of patients with clinoidal meningiomas and might form the basis for future clinical trials.

Although leptomeningeal melanin pigmentation is well-known, it is not described in the neurosurgical literature. Dark pigmentation native to these transparent membranes might have microsurgical relevance in identifying a plane of dissection.To describe the prevalence of leptomeningeal pigmentation and determine whether its recognition helps during microsurgical excision of extra-axial brain tumors.: This was a prospective cross-sectional observational study in cadavers and neurosurgical patients. Eight adult cadaveric brains were examined for leptomeningeal pigmentation and biopsies taken for histological studies. A total of 126 patients undergoing surgery for cerebellopontine angle and suprasellar lesions were included in the clinical study. The surgeon determined whether the recognition of pigmentation was useful during microneurosurgical arachnoid dissection.Seven of 8 cadavers (87.5%) had leptomeningeal pigmentation on the ventral pons, optic chiasm, lamina terminalis, olfactory tract, and gyrus rectus and infrequently on the cerebral convexities. The prevalence of pigmentation was 76.9% in the clinical study, was seen in all pediatric patients, and was significantly higher in males (P = 0.009), with no significant association with skin color. Immunochemistry identified the pigmentation as melanin. Recognition of this pigmentation was deemed to be useful during tumor excision in 78% of the cases.Leptomeningeal melanin pigmentation has a prevalence of 76% to 87% in the Indian population and is more often seen in younger males. It is most commonly identified overlying the ventral brain stem and optic chiasm. Recognition of its presence is helpful during arachnoid dissection during most cerebellopontine angle and suprasellar tumor resections.

Temporal lobe epilepsy (TLE) is the most prevalent form of human epilepsy, often accompanied by neurodegeneration in the hippocampus. Like other neurological diseases, TLE is expected to disrupt lipid homeostasis. However, the lipid architecture of the human TLE brain is relatively understudied, and the molecular mechanism of epileptogenesis is poorly understood. We performed desorption electrospray ionization mass spectrometry imaging of 39 fresh frozen surgical specimens of the human hippocampus to investigate lipid profiles in TLE with hippocampal sclerosis (n = 14) and control (non-TLE; n = 25) groups. In contrast to several previous studies on animal models of epilepsy, we report reduced expression of various important lipids, notably phosphatidylcholine (PC) and phosphatidylethanolamine (PE), in the human TLE hippocampus. In addition, metabolic pathway analysis suggested the possible dysregulation of the Kennedy pathway in TLE, resulting in striking reductions of PC and PE levels. This revelation opens up opportunities to further investigate the associated molecular mechanisms and possible therapeutic targets for TLE.

BACKGROUND Thyrotroph pituitary adenomas have been reported to be a rare cause of 'thyroid storms', causing myriad metabolic and autonomic disturbances. In this case, we describe the second reported case in literature of a 'GH storm' in an infarcted somatotroph adenoma.Case description: We describe a residual invasive somatotroph macroadenoma that underwent infarction, producing a dramatic elevation in serum GH levels. While infarction of adenomas may in some cases lead to remission, the patient went on to require re-surgery and re-radiation due to growth of the residual viable tumour.Conclusions- 'GH storms' are rare but interesting events that may occur in somatotroph adenomas. Infarction or apoplexy must be considered when managing residual adenomas.

Telomerase reverse transcriptase (TERT) promoter mutations, resulting in increased TERT activity, are known to be associated with many different cancer types, including among 70%–80% of glioblastomas and 60% each of bladder carcinomas and hepatocellular carcinomas.1–3 Increased TERT activity has also been associated with several molecular features including rare rearrangements, duplications and amplifications.1 However, of all the molecular changes, mutations in the TERT promoter region are known to be the most frequent. They are often restricted to two hotspots, 124 and 146 base pairs upstream of the transcription start sites, often referred to as C228T and C250T.1 2 The presence of these promoter mutations increases the similarity of these sites to the erythroblast transformation-specific (ETS) binding region, serving as a de novo binding site for ETS family transcription factors. Over time these mutations have assumed greater importance as markers of prognostication.4 In a recent study, Kikuchi et al 4 have clearly demonstrated that glioblastomas with TERT promoter mutations had a shorter progression-free survival (7 months vs 10 months; p=0.015) and overall survival (16 months vs 24 months; p=0.017) as compared with TERT wild-type glioblastomas. Such studies emphasise the need for accurate laboratory assays to detect these TERT promoter mutations. However, detection of TERT promoter mutation can be challenging in tissues with low tumour cellularity, high heterogeneity and poor DNA quality, especially if they are formalin-fixed.3 The problem is further compounded by the high guanine-cytosine (GC) content of the region (~80%) that can form strong secondary structures impairing strand denaturation. Validated assays that amplify GC-rich regions often use additives like the Q solution and locked nucleic acids (LNA)4 on a droplet digital PCR (ddPCR) …

Introduction Local anesthetic intranasal packing is used in transnasal surgery to reduce hemodynamic fluctuations. We hypothesized that the long acting local anesthetic levobupivacaine would provide superior hemodynamic stability and postoperative analgesia compared with lidocaine in endoscopic transnasal transsphenoidal (TNTS) surgery. Materials and methods In this prospective, randomized, double-blind trial, 48 patients undergoing TNTS surgery were allocated to the 2 groups to receive preoperative intranasal packing with 15 mL of 1.5% lidocaine or 0.5% levobupivacaine each mixed with 60 mg ephedrine. Heart rate and mean arterial blood pressure were recorded immediately before induction of anesthesia, at various time points throughout surgery, and at tracheal extubation. Bleeding in the surgical field, time to extubation, and postoperative pain were also assessed. Results There was no significant difference in heart rate between the lidocaine and levobupivacaine groups at any point. Mean arterial pressure was also similar between the 2 groups during surgery, whereas at extubation blood pressure was lower in the lidocaine compared with levobupivacaine group (85±10 vs. 96±16 mm Hg; P=0.0010). There were no differences between the 2 groups in the other outcome variables. Conclusions Preoperative intranasal packing with 1.5% lidocaine or 0.5% levobupivacaine provide similar hemodynamic stability throughout TNTS. Lidocaine packing may be more advantageous for hemodynamic stability during extubation.

To determine whether preoperative non-lateralizing scalp electroencephalography (EEG) influences seizure outcome following peri-insular hemispherotomy (PIH) in pediatric hemispheric epilepsy. Retrospective data was collected on all 45 pediatric patients who underwent PIH between 2005 and 2016. All underwent a basic pre-surgical evaluation consisting of detailed history and examination, neuropsychological assessment, MRI, and EEG. SPECT/PET, fRMI, or Wada testing were done in only eight patients. Seizure outcome was assessed using the Engel classification. Among those who underwent hemispherotomy, 20 (44%) were females. Mean age at surgery was 8 ± 4.3 years and mean duration of symptoms was 5.2 ± 3.7 years. The most common etiologies of hemispheric epilepsy were hemiconvulsion-hemiplegia epilepsy syndrome, Rasmussen encephalitis, and post-encephalitic sequelae, together comprising 27 (60%) patients. Among the 44 patients with follow-up data (mean duration 48 ± 33 months), seizure freedom (Engel class I) was attained by 41 (93.2%). Anti-epileptic medications were stopped or decreased in 36 (82%). Seventeen (38.6%) patients had non-lateralizing EEG. Seizure outcome was not related to lateralization of EEG activity. PIH provides excellent long-term seizure control in patients despite the presence of non-lateralizing epileptiform activity, although occurrence of acute postoperative seizures may be higher. Routine SPECT/PET may not be required in patients with a non-lateralizing EEG if there is good clinico-radiological concordance.

ObjectiveTo determine the usefulness of retinal nerve fibre layer (RNFL) thickness and a reliable cut-off value that can predict postoperative visual function improvement in patients with pituitary macroadenoma.Methods and AnalysisThis was a prospective observational study. Preoperative optical coherence tomography of the RNFL was performed in patients with pituitary macroadenoma. Postoperative visual function changes (acuity and visual fields) were identified using predefined criteria. Receiver operating characteristic curves were constructed for RNFL values to define the ideal cut-off value that predicted improvement. Other variables including preoperative visual acuity, mean deviation, visual field index and tumour volume were also analysed.ResultsTwenty-nine eligible subjects (58 eyes) were recruited. The mean (±SD) age was 43.9 (±12.85) years and 65.5% were male. The mean (±SE) follow-up duration was 20.8 (±6.42) months. RNFL thickness was significantly thinner in eyes with visual dysfunction and optic disc pallor. Better preoperative logarithmic minimum angle of resolution (logMAR) visual acuity, higher RNFL thickness and smaller tumour volume were associated with postoperative visual field improvement on univariate analysis; however, only mean RNFL thickness had significant association on multivariate analysis. None of the preoperative variables showed significant association with improvement in visual acuity. The best cut-off of mean RNFL thickness for visual field improvement was estimated at 81 μm with 73.1% sensitivity and 62.5% specificity.ConclusionPreoperative RNFL thickness can be an objective predictor of visual field outcomes in patients undergoing surgery for pituitary macroadenomas, with moderate sensitivity and specificity. It is, however, not a good predictor of visual acuity outcome.

BACKGROUND: Hybrid nerve sheath tumors (HNST) contain elements of more than one established sub-type of nerve sheath tumor and have been recently recognized in the 2016 WHO classification of central nervous system tumors. While common in the peripheral nerves and extracranial branches of cranial nerves, only one case has been previously documented of an intracranial HNST arising from a cranial nerve. CASE DESCRIPTION: We describe a large, multi-compartmental intracranial hybrid nerve sheath tumor arising from the trigeminal nerve in a 22-year-old lady who presented with clinical and radiological features suggestive of a right cerebellopontine angle mass. Histopathological examination following retrosigmoid excision of the tumor revealed histological and immunohistochemical features of a schwannoma and a perineurioma. CONCLUSIONS: HNSTs are likely to be underreported in the intracranial region. The clinical course of these tumors and the reason for their occurrence in this location are not known.

Purpose To estimate the prevalence of USP8, USP48, and BRAF mutations in patients with Cushing's disease (CD) from the Indian subcontinent, and determine their genotype-phenotype correlation. Methods We prospectively recruited 46 patients with CD who underwent surgery between September 2015 and July 2019 at our institute. Fresh frozen tumour tissue was obtained in all patients. Using Sanger sequencing, the presence of somatic USP8 mutations was documented and the frequency of USP48 and BRAF mutations in USP8 wild-type corticotroph adenomas was determined. Clinical, hormonal, and surgical data were then compared between USP8-, USP48- and BRAF-variant carriers and patients with wild-type tumours. Results Signature USP8 mutations were detected in 17 (37%) patients. Of the 29 USP8 wild-type adenomas, 4 (13.8%) harboured USP48 mutations, one of them being a splice-site mutation that has previously not been described. BRAF mutations were not found in any of the 29 patients. Corticotroph adenomas with USP8 mutations had a higher incidence of Crooke's hyaline change than wild-type tumours (70.6 vs. 37.9%, p = 0.032). Adenomas with USP48 mutations had a higher rate of cavernous sinus invasion than their wild-type counterparts (50 vs. 4%, p = 0.042). No other significant phenotypic difference could be established between mutant and wild-type tumours. Conclusions The prevalence of USP8 mutations in our series of patients with CD was 37%. The prevalence of USP48 mutations in USP8 wild-type adenomas was 13.8%, including a novel splice-site mutation. BRAF mutations were not found in any USP8 wild-type tumour. USP8-mutants showed significantly more Crooke's hyaline change and USP48-mutants were more likely to demonstrate cavernous sinus invasion.

Paragangliomas are tumours of extra-adrenal paraganglia. They may metastasize to the brain but primary paragangliomas are exceedingly rare in the supratentorial region and long-term outcomes after surgery is largely unknown. This description of an excellent outcome 13 years following surgery in a 40-year-old gentleman with a primary paraganglioma near the falx provides an important perspective on the value of gross total resection in these tumours. We also review the options for adjuvant therapy in tumours that cannot be excised completely.We describe a supratentorial paraganglioma in the parasagittal region in a 40-year-old gentleman who presented with clinical and radiological features suggestive of a right parafalcine meningioma. Histopathological examination following gross total excision of the tumour revealed histological and immunochemical features of a paraganglioma. A detailed search for a systemic primary was negative and the patient remains disease-free 13 years after the surgery.Differentiating between tumours arising primarily and those that are metastatic deposits in the central nervous system requires long-term follow-up and monitoring for the appearance of occult primary tumours. Gross total resection is likely to provide good long-term outcomes.

This report describes two patients with acute-onset ptosis, oculomotor dysfunction, ataxia and drowsiness, referable to the midbrain tegmentum. Both patients had previously suffered severe closed head injuries requiring craniotomy for cerebral decompression. Serial brain scans in both cases revealed a newly developing cleft in the midbrain, with features suggestive of abnormal cerebrospinal fluid (CSF) flow across the aqueduct. A trial of acetazolamide was initiated to reduce CSF production, followed by a third ventriculostomy for CSF diversion in one patient, which resulted in arrested disease progression and partial recovery. There are only two previous reports in the literature of midbrain clefts that developed as remote sequelae of head trauma. We postulate that altered CSF flow dynamics in the aqueduct, possibly related to changes in brain compliance, may be contributory. Early recognition and treatment may prevent irreversible structural injury and possible death.

Growth hormone (GH) hypersecretion from a pituitary adenoma results in acromegaly, an endocrinological disorder with multiple systemic manifestations that presents several unique challenges in terms of perioperative management and long term outcomes. Current guidelines provide stringent criteria for determining biochemical remission, necessitating an aggressive approach to management. Despite the development of several non-surgical therapies, transsphenoidal surgery, the endoscopic approach in particular, remains the primary line of treatment for rapid normalization of GH and Insulin-like growth factor with a low incidence of perioperative morbidity. Tumor size and invasiveness are important factors predicting surgical outcomes with better rates of postoperative remission seen in smaller and non-invasive tumors. Postoperative remission rates reported in literature with the 2020 consensus criteria vary from 30 to 85% probably reflecting varying prevalence rates of invasive tumors. Thus, a significant proportion of patients fail to achieve remission after surgery for whom treatment options for residual disease must be carefully considered. This review article discusses the surgical management of acromegaly and provides a summary of contemporary outcomes and current treatment controversies.

Background Diffusion-weighted imaging (DWI) provides information about the cellular density of tumors. This feature is useful in grading and identifying different tumor types. Purpose To assess the value of diffusion restriction and apparent diffusion coefficient (ADC) values in differentiating pediatric infratentorial tumors. Material and Methods This was a retrospective review of the magnetic resonance imaging (MRI) of 82 children (age range 1–16 years) with infratentorial tumors. Histopathological grading after surgical excision/biopsy was categorized as low grade (WHO grades I and II) (n = 31; 29 pilocytic astrocytomas, 2 ependymomas) and high grade (WHO grade III and IV) (n = 51; 40 medulloblastomas, 8 anaplastic ependymomas, 1 anaplastic astrocytoma, 2 atypical rhabdoid teratoid tumors [ATRT]). MRI features and ADC values were compared among tumor types and grades using a two-tailed t test, Mann–Whitney U test for continuous data and Chi-square test for categorical variables. Results Diffusion restriction and low ADC value was a feature of high-grade tumors ( P−3mm2/s and 0.661 × 10−3mm2/s, respectively. Using 0.9 × 10−3mm2/s as the cut-off value, the sensitivity, specificity, positive and negative predictive values for differentiating the grades was 87%, 100%, 100%, and 81.8%, respectively. Significant differences were found between the mean ADC values of the individual tumor types ( PConclusion ADC values and visual assessment of diffusion restriction are useful in tumor grading. The individual tumor types can be identified by an algorithmic approach, using DWI in conjunction with other described MRI features.

The optimal management of pediatric craniopharyngiomas remains controversial. This study aimed to characterize long-term outcomes in a contemporary cohort of children undergoing surgery for craniopharyngiomas. This was a retrospective review of 37 consecutive children who underwent surgery for craniopharyngioma with a median follow-up duration of 79 months (range 5–127 months). Patients were stratified by extent of resection (EOR) and need for adjuvant radiation therapy (RT). Imaging studies were reviewed to grade extent of hypothalamic involvement. Data on functional outcomes, pituitary function, and obesity were analyzed. Gross total resection was achieved in 16 patients (43.2%), near total resection in six patients (16.2%), and subtotal resection (STR) in 15 patients (40.5%). The recurrence-free survival rate was 81.1% and 70.3% at 5- and 10-year follow-up, respectively. Survival analysis showed superior disease control in patients undergoing STR + RT (p = 0.008). Functional outcomes were independent of EOR, postoperative RT or recurrence. Diabetes insipidus was present in 75% and 44.4% of patients required >2 hormone replacements at last follow-up. Obesity was present in 36.1% patients after treatment, and was associated with preoperative obesity (p = 0.019), preoperative hypothalamic involvement (p = 0.047) and STR + RT (p = 0.011). Gross or near total resection may be achieved safely in almost 60% of cases; however, radical surgery does not eliminate the risk of recurrence. Over long-term follow-up, STR + RT offers the best disease control rates. Patients with preoperative hypothalamic involvement, obesity, and those with tumors not amenable to radical resection are at risk for developing obesity on long-term follow-up.

Background and objective: Craniopharyngiomas are locally aggressive neuroepithelial tumors infiltrating nearby critical neurovascular structures. The majority of published surgical series deal with childhood-onset craniopharyngiomas, while the optimal surgical management for adult-onset tumors remains unclear. The aim of this paper is to summarize the main principles defining the surgical strategy for the management of craniopharyngiomas in adult patients through an extensive systematic literature review in order to formulate a series of recommendations. Material and methods: The MEDLINE database was systematically reviewed (January 1970–February 2019) to identify pertinent articles dealing with the surgical management of adult-onset craniopharyngiomas. A summary of literature evidence was proposed after discussion within the EANS skull base section. Results: The EANS task force formulated 13 recommendations and 4 suggestions. Treatment of these patients should be performed in tertiary referral centers. The endonasal approach is presently recommended for midline craniopharyngiomas because of the improved GTR and superior endocrinological and visual outcomes. The rate of CSF leak has strongly diminished with the use of the multilayer reconstruction technique. Transcranial approaches are recommended for tumors presenting lateral extensions or purely intraventricular. Independent of the technique, a maximal but hypothalamic-sparing resection should be performed to limit the occurrence of postoperative hypothalamic syndromes and metabolic complications. Similar principles should also be applied for tumor recurrences. Radiotherapy or intracystic agents are alternative treatments when no further surgery is possible. A multidisciplinary long-term follow-up is necessary.

Background and objective: The optimal management of large vestibular schwannomas continues to be debated. We constituted a task force comprising the members of the EANS skull base committee along with international experts to derive recommendations for the management of this problem from a European perspective. Material and methods: A systematic review of MEDLINE database, in compliance with the PRISMA guidelines, was performed. A subgroup analysis screening all surgical series published within the last 20 years (January 2000 to March 2020) was performed. Weighted summary rates for tumor resection, oncological control, and facial nerve preservation were determined using meta-analysis models. This data along with contemporary practice patterns were discussed within the task force to generate consensual recommendations regarding preoperative evaluations, optimal surgical strategy, and follow-up management. Results: Tumor classification grades should be systematically used in the perioperative management of patients, with large vestibular schwannomas (VS) defined as > 30 mm in the largest extrameatal diameter. Grading scales for pre- and postoperative hearing (AAO-HNS or GR) and facial nerve function (HB) are to be used for reporting functional outcome. There is a lack of consensus to support the superiority of any surgical strategy with respect to extent of resection and use of adjuvant radiosurgery. Intraoperative neuromonitoring needs to be routinely used to preserve neural function. Recommendations for postoperative clinico-radiological evaluations have been elucidated based on the surgical strategy employed. Conclusion: The main goal of management of large vestibular schwannomas should focus on maintaining/improving quality of life (QoL), making every attempt at facial/cochlear nerve functional preservation while ensuring optimal oncological control, thereby allowing to meet patient expectations. Despite the fact that this analysis yielded only a few Class B evidences and mostly expert opinions, it will guide practitioners to manage these patients and form the basis for future clinical trials., SCOPUS: re.j, info:eu-repo/semantics/published

Introduction: The optimal surgical treatment for giant pituitary neuroendocrine tumors(GPitNETs) is debated. Research question: The aim of this paper is to optimize the surgical management of these patients and to provide a consensus statement on behalf of the EANS Skull Base Section. Material and methods: We constituted a task force belonging to the EANS skull base committee to define some principles for the management of GPitNETs. A systematic review was performed according to PRISMA guidelines to perform a meta-analysis on surgical series of GPitNETs. Weighted summary rates were obtained for the pooled extent of resection and according to the surgical technique. These data were discussed to obtain recommendations after evaluation of the selected articles and discussion among the experts. Results: 20articles were included inourmeta-analysis, for a total of 1263 patients. The endoscopic endonasal technique was used in 40.3%of cases, the microscopic endonasal approach in 34%of cases, transcranial approaches in 18.7%and combined approaches in 7%of cases.No difference in terms of gross total resection (GTR) ratewas observedamong the different techniques. Pooled GTR rate was 36.6%, while a near total resection (NTR) was possible in 45.2% of cases. Cavernous sinus invasion was associated with a lower GTR rate (OR: 0.061). After surgery, 35% of patients had endocrinological improvement and 75.6% had visual improvement. Recurrent tumors were reported in 10% of cases Discussion and conclusion: After formal discussion in the working group, we recommend the treatment of G-Pit- NETs tumors with a more complex and multilobular structure in tertiary care centers. The endoscopic endonasal approach is the first option of treatment and extended approaches should be planned according to extension, morphology and consistency of the lesion. Transcranial approaches play a role in selected cases, with a multicompartmental morphology, subarachnoid invasion and extension lateral to the internal carotid artery and in the management of residual tumor apoplexy., Introduction: The optimal surgical treatment for giant pituitary neuroendocrine tumors(GPitNETs) is debated. Research question: The aim of this paper is to optimize the surgical management of these patients and to provide a consensus statement on behalf of the EANS Skull Base Section. Material and methods: We constituted a task force belonging to the EANS skull base committee to define some principles for the management of GPitNETs. A systematic review was performed according to PRISMA guidelines to perform a meta-analysis on surgical series of GPitNETs. Weighted summary rates were obtained for the pooled extent of resection and according to the surgical technique. These data were discussed to obtain recommendations after evaluation of the selected articles and discussion among the experts. Results: 20articles were included in our meta-analysis, for a total of 1263 patients. The endoscopic endonasal technique was used in 40.3% of cases, the microscopic endonasal approach in 34% of cases, transcranialapproaches in 18.7% and combined approaches in 7% of cases. No difference in terms of gross total resection (GTR) rate was observed among the different techniques. Pooled GTR rate was 36.6%, while a near total resection (NTR) was possible in 45.2% of cases. Cavernous sinus invasion was associated with a lower GTR rate (OR: 0.061). After surgery, 35% of patients had endocrinological improvement and 75.6% had visual improvement. Recurrent tumors were reported in 10% of cases. Discussion and conclusion: After formal discussion in the working group, we recommend the treatment of G-PitNETs tumors with a more complex and multilobular structure in tertiary care centers. The endoscopic endonasal approach is the first option of treatment and extended approaches should be planned according to extension, morphology and consistency of the lesion. Transcranial approaches play a role in selected cases, with a multicompartmental morphology, subarachnoid invasion and extension lateral to the internal carotid artery and in the management of residual tumor apoplexy.

Autism spectrum disorder (ASD) and temporal lobe epilepsy exhibit remarkable comorbidity, but for reasons not clearly understood. To reveal a common pathophysiological mechanism, we here describe and characterize an in vitro epileptiform activity in the rat hippocampus that exhibits common features with in vivo activity in rodent ASD models. We discovered the development of this activity in the CA1 region of horizontal slices after prolonged interictal-like epileptiform activity in the CA3 region that was provoked by incubation in high potassium artificial cerebrospinal fluid. The CA1 epileptiform bursts were insensitive to blockers of glutamatergic transmission, and were carried by synaptic as well as extrasynaptic, tonically activated gamma-aminobutyric acid type A (GABA(A)) receptors. The bursts bear resemblance to in vivo gamma-oscillatory activity found in rat ASD models with respect to their gamma frequency spectrum, their origin (in the CA1), and their sensitivity to blockers of cation-chloride pumps (NKCC1 and KCC2), as well as to oxytocin. Considering this bursting activity as an in vitro model for studying comorbidity between epilepsy and ASD may help to disentangle the intricate interactions that underlie the comorbidity between both diseases and suggests that extrasynaptic tonic GABAergic transmission could represent a potential target for ASD.

The World Health Organization (WHO) defines atypical pituitary adenomas as tumours with a MIB-1 labelling index ≥3%, p53 positivity and increased mitotic activity. Although a few reports have described the clinical and radiological correlates of atypia in pituitary adenomas, its impact on postoperative outcomes is not clearly defined. We reviewed preoperative and postoperative records of patients undergoing surgery for pituitary adenomas. Postoperative outcomes for functional adenomas (FPAs) were assessed according to contemporary definitions of remission and recurrence. For non-functional pituitary adenomas (NFPAs), extent of resection and disease progression were defined on the basis of postoperative magnetic resonance imaging. Of 394 patients included for analysis, 29 cases (7.4%) fulfilled criteria for atypia. Patients with atypical tumours were significantly younger than those with typical adenomas. Remission was possible in 47.4% of FPAs, and was unrelated to the presence of atypia. In NFPAs, local invasiveness was negatively associated with extent of resection (OR, 0.255; 95% CI, 0.086–0.753; p

Objective: To raise awareness of the clinical presentation of growth hormone (GH)-producing pituitary carcinoma and its unique clinical presentation.Methods: A case report of a GH-secreting pituitary carcinoma with predominant leptomeningeal spread presenting as persistent acromegaly post–macroadenoma excision and radiation therapy.Results: A 39-year-old male, diagnosed with a GH-secreting pituitary macroadenoma with acromegaly 3 years prior, presented with persisting acromegalic phenotypic features with associated diabetes mellitus and hypertension. He had undergone an endoscopic transnasal, transsphenoidal adenoma resection, followed 3 months later by conventional cranial irradiation at another center 2 years prior to his current presentation to us. Serum insulin-like growth factor 1 and post 1-hour 100-g oral glucose administration serum GH levels were 1,198 and 393 ng/mL, respectively. Magnetic resonance imaging of the brain with spine screening revealed an empty sella, diffuse enhancing cordal, posterior fossa and cauda-equina leptomeningeal thickening, suggesting lepto-meningeal spread of a primary neoplastic process. Cytologic examination of cerebrospinal fluid revealed GH-immunopositive malignant cells with pancytokeratin negativity. A diagnosis of GH-secreting pituitary carcinoma with leptomeningeal dissemination was made. He was initiated on intermittent short-acting subcutaneous octreotide and systemic chemotherapy with temozolamide 200 mg/m2 for 5 consecutive days every 28-days and concomitant skull and spine irradiation (total dose of 36 Grays in 20 fractions). His metabolic parameters improved following 3 cycles of chemotherapy. Interval assessment of disease status is awaited prior to the fourth temozolamide cycle.Conclusion: Pituitary carcinomas are rare. Clinico-biochemical presentation being indistinguishable from that of an adenoma, demonstration of metastasis is essential for diagnosis. Isolated leptomeningeal presentation is a unique presentation of GH-secreting pituitary carcinomas.Abbreviations: CSF = cerebrospinal fluid; GH = growth hormone; IGF-1 = insulin-like growth factor 1; MRI = magnetic resonance imaging

Akt is one of the most important downstream effectors of phosphatidylinositol 3-kinase/mTOR pathway. Hyperactivation and expression of this pathway are seen in a variety of neurological disorders including human temporal lobe epilepsy with hippocampal sclerosis (TLE-HS). Nevertheless, the expression and activation profiles of the Akt isoforms, Akt1, Akt2, and Akt3 and their functional roles in human TLE-HS have not been studied. We examined the protein expression and activation (phosphorylation) patterns of Akt and its isoforms in human hippocampal tissue from TLE and non-TLE patients. A phosphoproteomic approach followed by interactome analysis of each Akt isoform was used to understand protein-protein interactions and their role in TLE-HS pathology. Our results demonstrated activation of the Akt/mTOR pathway as well as activation of Akt downstream substrates like GSK3β, mTOR, and S6 in TLE-HS samples. Akt1 isoform levels were significantly increased in the TLE-HS samples as compared to the non-TLE samples. Most importantly, different isoforms were activated in different TLE-HS samples, Akt2 was activated in three samples, Akt2 and Akt1 were simultaneously activated in one sample and Akt3 was activated in two samples. Our phosphoproteomic screen across six TLE-HS samples identified 183 proteins phosphorylated by Akt isoforms, 29 of these proteins belong to cytoskeletal modification. Also, we were able to identify proteins of several other classes involved in glycolysis, neuronal development, protein folding and excitatory amino acid transport functions as Akt substrates. Taken together, our data offer clues to understand the role of Akt and its isoforms in underlying the pathology of TLE-HS and further, modulation of Akt/mTOR pathway using Akt isoforms specific inhibitors may offer a new therapeutic window for treatment of human TLE-HS.

The course of the vertebral artery after exiting from the C1 foramen transversarium and prior to entering the dura lends itself to compression in C1-2 instability. However, atlantoaxial dislocation presenting with vertebrobasilar insufficiency and posterior circulation stroke (PCS) is rare.In this retrospective study, we identified 96 patients with PCS who had complete radiological data. Ten (10.4%) patients had craniovertebral junction (CVJ) anomalies, of which six underwent surgery and four were managed conservatively. The clinical and functional outcomes were measured in the two groups.Left-sided strokes were seen in 7/10 patients, the majority of whom had left dominant vertebral arteries. The mean age at presentation in those with CVJ anomalies was 27.2 ± 12.8 years that was significantly lower than those without CVJ anomalies, 52.2 ± 14.5 years (p ≤ 0.001). The etiologies of PCS in those 50 years were CVJ anomalies (30%), atherosclerosis (30%) and vasculitis (27%); however, the overwhelming majority of strokes in the 50 year age group was atherosclerosis (91%). Postoperatively, there were no recurrent strokes in the operated patients, who also obtained significant clinical improvement on the modified Rankin Scale, Nurick Scale and modified McCormick Scale as compared to those who did not undergo surgery.Early diagnosis and surgical treatment of CVJ instability prevent recurrent strokes and improve outcomes in patients with PCS. Physicians and spine surgeons need to be sensitized regarding CVJ anomalies as a cause of PCS enabling early diagnosis with dynamic imaging particularly in the younger age group. These slides can be retrieved under Electronic Supplementary Material.

Background: Skills assessment forms an integral part of the exit examination in neurosurgical training programs. The established method of evaluating trainees for their clinical knowledge and surgical proficiency in the operating room is not feasible in the current time of SARS-COV19 pandemic. Objective: The feasibility of conducting such an assessment using case modules on an online meeting platform is discussed. Methods: Six candidates were evaluated on two consecutive days with two internal examiners located at the examination site and two external examiners situated at their own institutions elsewhere in the country. Clinical details, including images and videos of patients managed at our institute were recorded and provided to the candidates as case modules. Four sessions were conducted in the form of long and short cases, operative neurosurgery, neuroradiology, and neuropathology and a general viva-voce using "Zoom" (Zoom-Video-Communications, Inc. USA) platform. Feedback from the examinee and the examiners were obtained for any modification in the current format. Result: The online platform worked well without any interruption except for slight lag in the audio-visual system and occasional difficulty in using microphone and screen simultaneously. Trainees were able to interpret the clinical details and rated this format close to actual clinical evaluation. The examiners uniformly agreed that the online format for assessment was satisfactory and made some suggestions for improvement. Conclusion: Clinical and surgical skill evaluation is feasible using case modules and online meeting platforms. Use of original patient's data, images, videos demonstrating clinical signs, and operative procedures makes this assessment more objective.

To describe vertebral artery (VA) course at the C0–C1–C2 complex in patients with congenital bony craniovertebral junction (CVJ) anomalies. We studied the course of 169 VAs in 86 patients with congenital bony CVJ anomalies [basilar invagination (42), os odontoideum (33), and irreducible atlantoaxial dislocation (11)]. Occipitalized atlas occurred in 41 patients (30 complete and 11 partial). Using axial, coronal and sagittal three-dimensional computed tomography (3D-CT) angiograms, we traced the VA bilaterally at the CVJ and correlated the course to the presence or absence of occipitalization of the atlas. Of the 73 arteries associated with occipitalization of atlas, all had an abnormal course—58 (78.4 %) coursed through a canal within the C0–C1 fused complex and 15 (20.3 %) coursed below the C1 posterior arch, and it was absent unilaterally in one patient. There were 96 arteries associated with a non-occipitalized atlas and only 15 (15.3 %) were abnormal—eight coursed below the C1 posterior arch, four coursed above the C1 arch in the absence of a C1 foramen transversarium, one passed through a canal in C0–C1 and two arteries were absent unilaterally. Sixty vertebral arteries (34 on the right and 26 on the left side) had a redundant loop situated at a distance of ≥5 mm from the C1 lateral mass in patients with os odontoideum and irreducible atlantoaxial dislocation. In occipitalization of the atlas, the VA course is usually abnormal—typically passing through a canal within the C0–C1 fused complex or below the C1 arch. A redundant VA loop is more likely to be seen in os odontoideum and irreducible atlantoaxial dislocation. Careful study of the vertebral artery course with 3D CT angiography is mandatory while contemplating CVJ realignment surgery in congenital anomalies of the CVJ.

Objective To describe the technique of endoscopic transmaxillary temporalis muscle flap transposition for the repair of a persistent postoperative sphenoidal cerebrospinal fluid leak. Design The repair of a recurrent cerebrospinal fluid leak for a patient who had undergone endoscopic transsphenoidal excision of an invasive silent corticotroph Hardy C and Knosp Grade IV pituitary adenoma was undertaken. The patient had completed postoperative radiotherapy for the residual tumor and presented with cerebrospinal fluid leak, 1 year later. The initial two attempts to repair the cerebrospinal fluid leak with free grafts failed. Therefore, an endoscopic transmaxillary transposition of the temporalis muscle flap was attempted to stop the cerebrospinal fluid leak. Results The endoscopic transmaxillary transposition of the vascularized temporalis muscle flap onto the cerebrospinal fluid leak repair site resulted in successful closure of the cerebrospinal fluid leak. Conclusion Endoscopic transmaxillary transposition of the temporalis flap resulted in closure of recurrent cerebrospinal fluid leak in a patient with recurrent pituitary adenoma, who had undergone previous surgery and radiotherapy. This technique has advantages over the endoscopic transpterygoid transposition of the same flap and could be used as a complementary technique in selected patients.

Objectives This study aims to describe the types of anterior skull base defects following expanded endoscopic approaches (EEA) and to outline the techniques involved in the repair of these defects. Design We retrospectively analyzed 63 cases of endoscopic skull base reconstruction (ESBR) following tumor excision, done from September 2011 to January 2015. These tumors consisted of 14 pituitary adenomas, 20 craniopharyngiomas, and 29 other miscellaneous tumors. The classification of skull base defects by Tabaee et al and the classification of cerebrospinal fluid (CSF) leaks by Esposito et al were considered during the ESBR. Recurrence of CSF leak was considered as failure of reconstruction. Results The 63 skull base defects included in this study occurred following EEA for tumor excision. Failure of reconstruction occurred in 6 six patients. All were successfully repaired, however, three patients in this series died due to tumor-related complications. Conclusion The adherence to the general principles of reconstruction, appreciating the subtle differences in the nature of the various defects and the ability to adopt different strategies are the prerequisites for the successful closure of skull base defects.

The most common presenting form of neurocysticercosis in the Indian subcontinent is a solitary cysticercus granuloma (SCG). Patients with typical SCGs almost never require any form of surgical intervention. Herein, we report an extremely rare case of bacterial superinfection of a left frontal SCG in a 23-year-old female, resulting in severe perilesional edema and mass effect. The patient had to undergo an emergency left decompressive hemicraniectomy and excision of the infected granuloma. Serum enzyme-linked immunoelectrotransfer blot (EITB) for cysticercal antibodies was positive and histopathological examination of the lesion revealed a cysticercus. The culture of the pus from within the lesion grew vancomycin-resistant Enterococcus spp. for which she was treated with linezolid for 6 weeks. At 6 months follow-up, she had residual motor dysphasia, right homonymous hemianopia, and right hemiparesis but was steadily improving. Secondary bacterial infection of an SCG is very uncommon and can be devastating. A high index of suspicion is therefore required when there is disproportionate perilesional edema and mass effect.

Post-operative hyponatremia (serum sodium130 mEq/L) contributes to morbidity and prolongs the hospital stay of patients undergoing neurosurgical procedures. Syndrome of inappropriate anti-diuretic hormone secretion (SIADH) and cerebral salt wasting (CSW) commonly occur in the post-operative setting. While patients with SIADH are either euvolemic or hypervolemic, patients with CSW are always hypovolemic. The treatment of these two conditions is radically different. Patients with SIADH need fluid restriction, while patients with CSW need fluid replacement. As current diagnostic methods do not clearly distinguish between SIADH and CSW, we looked at N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and uric acid as biochemical markers for estimating the volume status of patients developing hyponatremia in the postoperative period.In this study, we used a cohort design and carried it out in two phases over a period of 30 months (August 2011-February 2014). Thirty-one patients with hyponatremia were recruited into the study. In Phase1, 10 patients were diagnosed to have either SIADH or CSW based on their central venous pressure (CVP). In all of them, blood for NT-proBNP was collected prior to starting treatment. At a later stage, the NT-proBNP results were compared with central venous pressure (CVP) and the clinical diagnosis. Patients diagnosed to have SIADH (CVP5cm) had NT-proBNP levels125pg/ml and those with a diagnosis of CSW (CVP5cm) had NT-proBNP levels125pg/ml. In Phase2, 21 patients were categorized and treated according to their NT-proBNP levels. Those with NT-proBNP levels125 pg/ml were treated as SIADH, and those with NT-proBNP levels125 pg/ml were treated as CSW.In Phase 1, NT-proBNP could detect hypovolemia in patients with CSW with 100% sensitivity and 66.7% specificity (P0.07). In Phase 2, NT-proBNP could detect hypovolemia in patients with CSW with 90% sensitivity and 100% specificity (P0.001). Combining the results of Phase 1 and Phase 2, NT-proBNP could diagnose CSW with 87.50% sensitivity and 93.33% specificity (P0.001). The positive predictive value was 93.33% and the negative predictive value was 87.50%.NT Pro-BNP is a quick and convenient assay to differentiate SIADH and CSW. We need a larger sample size to correctly characterize the cut off value. Uric acid cannot be used to distinguish between SIADH and CSW.

Intraoperative cerebrospinal fluid (CSF) leaks are a frequent cause of morbidity in patients undergoing transsphenoidal surgery. This prospective study was performed to examine the impact of intraoperative lumbar subarachnoid drainage (LSAD) on the incidence of this complication and on the extent of resection in patients undergoing endoscopic transsphenoidal surgery for pituitary adenomas.This prospective study was conducted in a single large academic medical center. All patients with pituitary adenomas who had not undergone prior transsphenoidal surgery were eligible for inclusion in the study. Patients were randomly assigned to undergo transsphenoidal surgery with intraoperative lumbar drain insertion (LSAD group) or no lumbar drain insertion (no LSAD group). An otolaryngologist independently determined the occurrence of an intraoperative CSF leak. Extent of tumor resection was determined by volumetric analysis of postoperative magnetic resonance images in patients with nonfunctional tumors or functional adenomas with a large suprasellar component.Sixty patients were eligible for inclusion, of which 30 were assigned to the LSAD group and 30 to the no LSAD group. There were no statistically significant differences in patient demographics, tumor pathology, or radiology between the two groups. The LSAD catheter was successfully inserted in all patients in the LSAD group. Intraoperative CSF drainage significantly reduced the incidence of CSF leak from 46.7% in the no LSAD group to 3.3% in the LSAD group (P0.001). However, there were no statistically significant differences in the incidence of postoperative CSF rhinorrhea between the two groups. There were no major catheter-related complications. There was no statistically significant difference in the extent of resection between the two groups.Controlled intraoperative CSF drainage significantly reduces the incidence of intraoperative CSF leakage in patients undergoing endoscopic transsphenoidal surgery for pituitary adenomas.

This study was performed to examine patient outcomes following pure endoscopic transsphenoidal surgery (ETS) for Cushing's disease (CD).We studied 64 consecutive patients who underwent 69 endoscopic transsphenoidal procedures. Radiological evaluation comprised detailed examination of preoperative magnetic resonance images (MRI), including positron emission tomography (PET) for select cases. Inferior petrosal sinus sampling (IPSS) was not performed for any patient. Remission was defined by the presence of hypocortisolemia with requirement for steroid replacement therapy or eucortisolemia with suppression to1.8 μg/dl after 1 mg dexamethasone on evaluation at least 3 months after surgery.Preoperative MRI was abnormal in 87.5 % of cases and included 11 macroadenomas (17.2 %). PET was used to localize the adenoma in four cases. For microadenomas, operative procedures executed were as follows: selective adenomectomy (n = 15), enlarged adenomectomy (n = 21) and subtotal/hemihypophysectomy (n = 17). Overall, pathological confirmation of an adenoma was possible in 58 patients (90.6 %). Forty-nine patients (76.6 %) developed hypocortisolemia (5 μg/dl) in the early postoperative period. Mean follow-up was 20 months (range 6-18 months). Remission was confirmed in 79.7 % of the 59 cases followed up for3 months and was superior for microadenomas (86.4 %) versus macroadenomas (55.6 %) and equivocal MRI adenomas (66.7 %). Postoperative CSF rhinorrhea occurred in five patients, and new endocrine deficits were noted in 17.1 % patients. A nadir postoperative cortisol2 μg/dl in the 1st week after surgery was highly predictive of remission (p = 0.001).ETS allows for enhanced intrasellar identification of adenomatous tissue, providing remission rates that are comparable to traditional microsurgery for CD. The best predictor of remission remains induction of profound hypocortisolemia in the early postoperative period.

We reviewed clinical, imaging and histopathology details of 297 patients who underwent surgery for pituitary adenomas, with an equal distribution of functional and non-functioning tumors, to examine clinicopathological correlates of extrasellar growth. Knosp grades of 3 and 4 on MRI defined cavernous sinus invasion, Hardy grades of C and D defined significant suprasellar/subfrontal extension, and intraoperative evidence of tumor eroding through the clivus or sellar floor defined infrasellar invasion. Disease status at follow-up was known in 246 patients overall, including 35 patients who were evaluated for progression of residual disease on serial imaging. On univariate analysis, we found several statistically significant associations (p < 0.05) including adenoma size with age, sex and tumor protein p53 reactivity; cavernous sinus invasion with size, non-functional status, increased mitotic activity, an elevated MIB-1 proliferation index and p53 reactivity; suprasellar/subfrontal extension with p53 reactivity; and infrasellar invasion with age and tumor size. When adjusting for confounders with logistic regression, several significant associations were evident including adenoma size with male sex and p53 reactivity; cavernous sinus invasion with size and elevated MIB-1 proliferation index; suprasellar/subfrontal extension with p53 reactivity; and infrasellar invasion with adenoma size alone. Patients with early progression of postoperative residual tumor were younger with a non-significant trend towards higher MIB-1 proliferation indices. Individual patterns of extrasellar growth in pituitary adenomas are associated with unique clinical and immunohistochemical profiles. Younger patients with elevated MIB-1 values are probably at high risk for early recurrence of non-functioning tumors. Definitions of atypia must be standardized before more robust assumptions about tumor biology can be established.