Endoscopic endonasal surgery for prolactinomas: prognostic factors for disease control and management of persistent disease.

Only a limited number of studies have focused on the results of the Endoscopic Endonasal Approach (EEA) for treatment of prolactinomas. We sought to assess the effectiveness of EEA for prolactinoma surgery, identify factors for disease remission, and present our approach for the management of persistent disease. Forty-seven prolactinomas operated over 10 years, with a mean follow-up of 59.9 months, were included. The primary endpoints were early disease remission and remission at last follow-up. Resistance/intolerance to DA were surgical indications in 76.7%. Disease remission was achieved in 80% of microprolactinomas and 100% of microprolactinomas enclosed by the pituitary. Early disease remission was correlated with female gender (p=0.03), lower preoperative PRL levels (p=0.014), microadenoma (p=0.001), lack of radiological hemorrhage (p=0.001), absence of cavernous sinus (CS) invasion (p<0.001), and extent of resection (EOR) (p<0.001). Persistent disease was reported in 48.9% of patients, with 47% of them achieving remission at last follow-up with DA therapy alone. Repeat EEA and/or radiotherapy were utilized in 6 patients, with 66.7% achieving remission. Last follow-up remission was achieved in 76.6%, with symptomatic improvement in 95.8%. Factors predicting last follow-up remission were no previous operation (p=0.001), absence of CS invasion (p=0.01), and EOR (p<0.001). Surgery is effective for disease control in microprolactinomas. In giant and invasive tumors, it may significantly reduce the tumor volume. A multidisciplinary approach may lead to long-term disease control in three-quarters of patients, with symptomatic improvement in an even greater proportion.

Atonic seizures in children: a meta-analysis comparing corpus callosotomy to vagus nerve stimulation.

PURPOSE: Atonic seizures are associated with a particularly poor response to medical treatment. We performed a systematic review and meta-analysis to compare the efficacy of corpus callosotomy (CC) and vagus nerve stimulation (VNS) in the management of atonic seizures in the pediatric population. METHODS: A literature search was performed in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and recommendations, focusing on atonic seizures, CC, and VNS in pediatric populations. Pertinent clinical data were extracted and analyzed. Pooled effects between groups were calculated as standardized error (SE) with 95% confidence intervals (CIs). To assess for statistical significance, the Z-test was performed, using the pooled effect size (ES) and 95% CI for each intervention. RESULTS: A total of 31 studies met the inclusion criteria, with 24 studies encompassing 425 children treated with CC and 7 studies encompassing 108 children treated with VNS. Twenty-four studies were included in a meta-analysis. There was a statistically significant difference in the primary outcome of atonic seizure control in favor of CC (overall effect size (ES) 0.73, 95% CI 0.69-0.77 for CC, ES 0.4, 95% CI 0.28-0.51 for VNS, p = 0.003). There was a higher rate of complications requiring reoperation in the CC cohort (6.6% vs. 3.8%) and a 14% rate of symptomatic disconnection syndrome. CONCLUSIONS: While both techniques are safe, CC provides a much higher chance of effectively managing this morbid seizure type albeit with a higher risk of re-operation and disconnection syndrome.

Erratum to: Lessons learned from contemporary glioblastoma randomized clinical trials through systematic review and network meta-analysis: part 1 newly diagnosed disease.

[This corrects the article DOI: 10.1093/noajnl/vdab028.].

Lessons learned from contemporary glioblastoma randomized clinical trials through systematic review and network meta-analysis: part 2 newly diagnosed disease.

BACKGROUND: Glioblastoma (GB) is the most common malignant brain tumor with a dismal prognosis despite standard of care (SOC). Here we used a network meta-analysis on treatments from randomized control trials (RCTs) to assess the effect on overall survival (OS) and progression-free survival (PFS) beyond the SOC. METHODS: We included RCTs that investigated the addition of a new treatment to the SOC in patients with newly diagnosed GB. Our primary outcome was OS, with secondary outcomes including PFS and adverse reactions. Hazard ratio (HR) and its 95% confidence interval (CI) regarding OS and PFS were extracted from each paper. We utilized a frequentist network meta-analysis. We planned a subgroup analysis based on O6-methylguanine-DNA methyl-transferase (MGMT) status. We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses. RESULTS: Twenty-one studies were included representing a total of 7403 patients with GB. There was significant heterogeneity among studies impacting important factors such as timing of randomization and sample size. A confidence analysis on the network meta-analysis results revealed a score of low or very low for all treatment comparisons, across subgroups. Allowing for the heterogeneity within the study population, alkylating nitrosoureas (Lomustine and ACNU) and tumor-treating field improved both OS (HR = 0.53, 95% CI 0.33-0.84 and HR = 0.63 95% CI 0.42-0.94, respectively) and PFS (HR = 0.88, 95% CI 0.77-1.00 and HR = 0.63 95% CI 0.52-0.76, respectively). CONCLUSIONS: Our analysis highlights the numerous studies performed on newly diagnosed GB, with no proven consensus treatment that is superior to the current SOC. Intertrial heterogeneity raises the need for better standardization in neuro-oncology studies.

Lessons learned from contemporary glioblastoma randomized clinical trials through systematic review and network meta-analysis: part 2 recurrent glioblastoma.

BACKGROUND: There exists no consensus standard of treatment for patients with recurrent glioblastoma (GB). Here we used a network meta-analysis on treatments from randomized control trials (RCTs) to assess the effect on overall survival (OS) and progression-free survival (PFS) to determine if any consensus treatment can be determined for recurrent GB. METHODS: We included all recurrent GB RCTs with at least 20 patients in each arm, and for whom patients underwent standard of care at the time of their GB initial diagnosis. Our primary outcome was OS, with secondary outcomes including PFS and adverse reactions. Hazard ratio (HR) and its 95% confidence interval (CI) of the comparison of study arms regarding OS and PFS were extracted from each paper. For comparative efficacy analysis, we utilized a frequentist network meta-analysis, an extension of the classic pair-wise meta-analysis. We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses. RESULTS: Fifteen studies were included representing 29 separate treatment arms and 2194 patients. In our network meta-analysis, combination treatment with tumor-treating field and Vascular endothelial growth factor (VEGF) inhibitor ranked first in improving OS (P = .80). Concomitant anti-VEGF and Lomustine treatment was superior to Lomustine alone for extending PFS (HR 0.57, 95% CI 0.41-0.79) and ranked first in improving PFS compared to other included treatments (P = .86). CONCLUSIONS: Our analysis highlights the numerous studies performed on recurrent GB, with no proven consensus treatment that is superior to the current SOC. Intertrial heterogeneity precludes drawing strong conclusions, and confidence analysis was low to very low. Further confirmation by future trials is recommended for our exploratory results.

Adult isocitrate dehydrogenase-mutant brainstem glioma: illustrative case.

BACKGROUND: Adult brainstem gliomas are rare entities that demonstrate heterogeneous biology and appear to be distinct from both their pediatric counterparts and adult supratentorial gliomas. Although the role of histone 3 mutations is being increasingly understood in this disease, the effect of isocitrate dehydrogenase (IDH) mutations remains unclear, largely because of limited data. OBSERVATIONS: The authors present the case of a 29-year-old male with an IDH1-mutant, World Health Organization grade III anaplastic astrocytoma in the dorsal medulla, and they provide a review of the available literature on adult IDH-mutant brainstem glioma. The authors have amassed a cohort of 15 such patients, 7 of whom have survival data available. Median survival is 56 months in this small cohort, which is similar to that for IDH wild-type adult brainstem gliomas. LESSONS: The authors' work reenforces previous literature suggesting that the role of IDH mutation in glioma differs between brainstem and supratentorial lesions. Therefore, the authors advocate that adult brainstem gliomas be studied in terms of major molecular subgroups (including IDH mutant) because these gliomas may exhibit fundamental differences from each other, from pediatric brainstem gliomas, and from adult supratentorial gliomas.

Pediatric multicompartmental trigeminal schwannoma: illustrative case.

BACKGROUND: Trigeminal schwannoma (TS) is an uncommon and histologically benign intracranial lesion that can involve any segment of the fifth cranial nerve. Given its often impressive size at diagnosis and frequent involvement of critical neurovascular structures of the skull base, it represents a challenging entity to treat. Pediatric TS is particularly rare and presents unique challenges. Similarly, tumors with extension into multiple compartments (e.g., middle cranial fossa, posterior cranial fossa, extracranial spaces) are notoriously difficult to treat surgically. Combined or staged surgical approaches are typically required to address them, with radiosurgical treatment as an adjunct. OBSERVATIONS: The authors presented the unusual case of a 9-year-old boy with a large, recurrent multicompartmental TS involving Meckel's cave, the cerebellopontine angle, and the infratemporal fossa. Near-total resection was achieved using a frontotemporal-orbitozygomatic craniotomy with a combined interdural and extradural approach. LESSONS: The case report adds to the current literature on multicompartmental TSs in children and their management. The authors also provided a simplified classification of TS that can be generalized to other skull base tumors. Given a lack of precedent, the authors intended to add to the discussion regarding surgical management of these rare and challenging skull base lesions.

Burr holes, bone flaps, and goose quills: Dr Frank Turnbull, Vancouver's first neurosurgeon.

Dr Frank Turnbull was a pioneer neurosurgeon - the first neurosurgeon in Vancouver, Canada. He started his practice in 1933 after spending time during a neurosurgical 'residency' with Dr Kenneth Mackenzie, Canada's first neurosurgeon. Dr Turnbull practiced at a time when the perception of his speciality was dim, and the resources available to him were limited. However, Dr Turnbull overcame these obstacles, and two World Wars to help change the landscape of neurosurgery in the northwest Canada, and his career achievements also extend into medical politics and medical education. This paper documents the life and adventures of Dr Frank Turnbull, pioneer neurosurgeon.

Long-term outcomes after surgery for catastrophic epilepsy in infants: institutional experience and review of the literature.

OBJECTIVE: Uncontrolled epilepsy is associated with serious deleterious effects on the neurological development of infants and has been described as "catastrophic epilepsy." Recently, there has been increased emphasis on early surgical interventions to preserve or rescue neurodevelopmental outcomes in infants with early intractable epilepsy. The enthusiasm for early treatments is often tempered by concerns regarding the morbidity of neurosurgical procedures in very young patients. Here, the authors report outcomes following the surgical management of infants (younger than 1 year). METHODS: The authors performed a retrospective review of patients younger than 1 year of age who underwent surgery for epilepsy at Miami (Nicklaus) Children's Hospital and Jackson Memorial Hospital between 1994 and 2018. Patient demographics, including the type of interventions, were recorded. Seizure outcomes (at last follow-up and at 1 year postoperatively) as well as complications are reported. RESULTS: Thirty-eight infants (median age 5.9 months) underwent a spectrum of surgical interventions, including hemispherectomy (n = 17), focal resection (n = 13), and multilobe resections (n = 8), with a mean follow-up duration of 9.1 years. Hemimegalencephaly and cortical dysplasia were the most commonly encountered pathologies. Surgery for catastrophic epilepsy resulted in complete resolution of seizures in 68% (n = 26) of patients, and 76% (n = 29) had a greater than 90% reduction in seizure frequency. Overall mortality and morbidity were 0% and 10%, respectively. The latter included infections (n = 2), infarct (n = 1), and immediate reoperation for seizures (n = 1). CONCLUSIONS: Surgical intervention for catastrophic epilepsy in infants remains safe, efficacious, and durable. The authors' work provides the longest follow-up of such a series on infants to date and compares favorably with previously published series.