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.

Pituitary metastases: a case series and scoping review.

PURPOSE: To understand the natural history and optimal treatment strategy for pituitary gland metastasis. METHODS: We performed both a retrospective chart review of patients treated at our institution and a scoping review of the topic. RESULTS: The retrospective review identified seven patients with an average age of 59.6 years. Primary histologies included breast cancer (4), melanoma (1), renal cell carcinoma (1), and sarcoma (1). Two patients had anterior pituitary endocrine dysfunction, one of whom was the only patient with visual symptoms. All patients were treated with radiosurgery and two also underwent surgical resection. Overall survival ranged from 6.5 to 117 months. Literature review identified 166 patients from 71 studies. The most common primary cancer was lung (27.7%), followed by breast (18.7%) and renal (14.5%) cancer. 107 presented with endocrine dysfunction, including 41 cases of diabetes insipidus and 55 cases of hypopituitarism. 110 presented with visual compromise. 107 patients received radiotherapy, 96 underwent surgical resection and 44 received systemic chemotherapy/immunotherapy. Surgery was significantly associated with an increased likelihood of vision improvement and a decreased likelihood of endocrine normalization. Radiographic regression predicted visual improvement. Median overall survival was 9.9 months (range: 0.2-96). CONCLUSIONS: This scoping review showed that both radiosurgery and surgical resection have been frequently used to treat pituitary metastases with good response. Vision improvement is more likely to happen following surgical resection, likely at the expense of endocrine dysfunction. Despite treatment and radiographic response, patient survival remains less than a year.

Endoscopic Treatment of Rathke's Cleft Cysts: The Case for Simple Fenestration.

BACKGROUND: Rathke's cleft cysts (RCC) arise from the pars intermedia because of incomplete regression of the embryologic Rathke pouch. A subset of RCC becomes symptomatic causing headaches, visual and endocrinological disturbances such that surgical intervention is indicated. Several points in surgical management remain controversial including operative strategy (simple fenestration (SF) vs complete cyst wall resection (CWR)) as well as reconstructive techniques. METHODS: A retrospective analysis was conducted of pathologically confirmed RCC operated on by endoscopic endonasal approach from 2006 to 2019. Pre-operative symptoms, imaging characteristics, operative strategy, symptom response, complications and recurrences were recorded. RESULTS: Thirty-nine patients were identified. Thirty-three underwent SF and six underwent CWR. Worsening pituitary function was significantly increased with CWR (50%) compared to SF (3%) (p = 0.008). All patients underwent "closed" reconstruction with a post-operative CSF leak rate of 5% (3% SF vs 16% CWR, p = 0.287). Six (15%) recurrences necessitating surgery were reported. Recurrence rates stratified by surgical technique (18% SF vs 0% CWR, p = 0.564) were not found to be significantly different. CONCLUSIONS: The current series illustrates variability in the surgical management of RCCs. SF with closed reconstruction is a reasonable operative strategy for most symptomatic RCCs cases while CWR can be reserved for selected cases.

The Unified Visual Function Scale Assessments Show Inter- and Intraobserver Agreement and Correlate with Patient Quality of Life in Skull Base Parasellar Tumors.

Introduction The authors have previously described the Unified Visual Function Scale (UVFS). Here, we assessed intra- and interobserver reliability of the scale, and investigated correlations with patient quality of life (QoL). Methods Eight healthcare practitioners independently applied the UVFS in 20 representative cases from our parasellar meningioma series. Scoring was compared with consensus grades assigned by lead authors. Inter- and intraobserver agreement was measured using intraclass correlation coefficient (ICC), Fleiss's κ, and Cohen's κ, respectively. Patient QoL was assessed Visual Function Questionnaire 25 (VFQ-25) or Activities of Daily Vision Scale (ADVS), and correlated with UVFS grades for each eye. Results The interobserver ICC was 0.734 (95% confidence interval [CI]: 0.652-0.811), with Fleiss's κ of 0.758, 0.691, and 0.899 for grades A, B, and C, respectively. The intraobserver ICC was 0.758 (95% CI: 0.638-0.872), and Fleiss's κ was 0.604, 0.268, and 0.910 for grades A, B, and C respectively. The Cohen's κ for agreement between UVFS category grades and consensus grades was 0.816 (95 CI: 0.698-0.934). Survey response rate was 51% (27/53). The UVFS demonstrated strong correlation with VFQ-25 subdivisions general vision ( r = 0.7712), near activities ( r = 0.7262), peripheral vision ( r = 0.6722), and driving ( r = 0.6608), and also demonstrated strong correlation with the overall ADVS score ( r = 0.5902). Conclusion This study shows that the UVFS is valid within a small subset of observers, and accurately reflects patient QoL. It is robust and practical, which make it suitable for broad implementation.

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.

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.

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.

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.

Bilateral cervical facet dislocations at two adjacent levels: A case report.

BACKGROUND: Cervical facet dislocations are rare in patients sustaining traumatic subaxial injuries. They occur due to hyperflexion-distraction and can occur unilaterally or bilaterally resulting in significant spinal instability. Bilateral facet dislocations at one level are less common than unilateral dislocations, while bilateral facet dislocations at adjacent spinal levels have only been reported twice in literature. CASE DESCRIPTION: A 31-year-old male presented with bilateral facet dislocations at two adjacent cervical levels (C6/C7 and C7/T1) following a fall from 40 to 50 feet. The patient had undergone a C6/C7 disk arthroplasty a few weeks before the traumatic event. CONCLUSION: Here, we present the unique case of cervical bilateral jumped facets occurring at two adjacent levels (i.e., C6-C7 and C7-T1). Notably, the antecedent cervical C6-C7 arthroplasty likely contributed to the altered load distribution, leading to this unusual instance of bilateral adjacent level facet dislocations. In such cases, surgical reduction and fixation may prove technically challenging warranting, therefore, careful preoperative planning.

Natural History, Multimodal Management, and Quality of Life Outcomes of Trigeminal Schwannomas.

Background Trigeminal schwannomas are the second most common among intracranial schwannomas. These can arise from anywhere between the root and the distal extracranial branches of the trigeminal nerve. Clinical presentation depends on location and size, including but not limited to facial hypesthesia or pain, headaches, dizziness, ataxia, and diplopia. Literature is strikingly scant discussing the natural history of these lesions, while the treatment goals are heavily dependent on tumor presentation. Management decisions must be individualized to each tumor and each patient, while attempting to maximize the quality of life. We present the natural history of these lesions as well as their management by surgical resection or radiation therapy, and report long-term quality of life outcomes. Methods Between 2001 and 2015, 24 patients (66.7% female) with trigeminal schwannomas were diagnosed and managed at Vancouver General Hospital. We analyzed the clinical presentation, surgical results, resection rates, patient quality of life, and complications. To complete the evaluation, we prospectively collected 36-Item Short Form Health Survey (SF-36) quality of life assessments for comparison. Results We identified 12 patients treated with a craniotomy and surgical resection, 4 were treated with radiation therapy, while 8 patients were followed by observation. Mean age of study cohort was 49.2 years (range, 23-79 years), and most patients presented with facial hypesthesia (54.2%) and headaches (37.5%), while 37.5% were incidental findings. There were no major differences in patient demographics between the three groups. Patients offered surgery had larger lesions (mean diameter, 3.4 ± 1.1 cm) when compared with those that were irradiated or observed, and were more likely to have extracranial extension. Overall patient quality of life improved following treatment (ΔSF-36 + 12.9) at 3.9 years. Conclusions The treatment goals of trigeminal schwannomas focus on improvement in neurologic symptoms, relief of mass effect, and preservation of cranial nerve function. We demonstrate that smaller lesions found incidentally with minimal symptoms can be followed safely with serial imaging, with 1 of 9 (11.1%) progressing to require treatment over the course of 7.1 years. Management of trigeminal schwannomas should be individualized with an involvement of a multidisciplinary skull base team.

A novel scale for describing visual outcomes in patients following resection of lesions affecting the optic apparatus: the Unified Visual Function Scale.

OBJECTIVEHistorically, descriptions of visual acuity and visual field change following intracranial procedures have been very rudimentary. Clinicians and researchers have often used basic descriptions, such as "improved," "worsened," and "unchanged," to describe outcomes following resections of tumors affecting the optic apparatus. These descriptors are vague, difficult to quantify, and challenging to apply in a clinical perspective. Several groups have attempted to combine visual acuity and visual fields into a single assessment score, but these are not user-friendly. The authors present a novel way to describe a patient's visual function as a combination of visual acuity and visual field assessment that is simple to use and can be used by surgeons and researchers to gauge visual outcomes following tumor resection.METHODSVisual acuity and visual fields were combined into 3 categories designed around the definitions of legal blindness and fitness to drive in Canada. The authors then applied the scale (the Unified Visual Function Scale, or UVFS) to their previously published case series of perisellar meningiomas to document and test overall visual outcomes for patients undergoing tumor resection. The results were compared with previously documented visual loss scales in the literature.RESULTSUsing the UVFS the authors were able to capture the overall visual change; the scale was sensitive enough to define the overall visual improvement or worsening quantitatively, using categories that are clinically relevant and understandable.CONCLUSIONSThe UVFS is a robust way to assess a patient's vision, combining visual fields and acuity. The implementation of pre- and postoperative assessment is sensitive enough to assess overall change while also providing clinically relevant information for surgeons, and allows for comparisons between treatment groups.

Medical and surgical management of acute spinal injury during pregnancy: A case series in a third-world country.

BACKGROUND: There is scant literature describing the management of acute spinal injury in pregnant patients. Here, we report our experience with five cases of pregnant patients including three females who suffered acute traumatic spinal cord injuries (SCIs). METHODS: This retrospective study evaluated five pregnant women presenting with traumatic spinal injuries over a 16-month period. All were assessed using the International Standards for Neurological Classification of Spinal Cord Injury Patients and the American Spine Injury Association Impairment Scale (AIS). RESULTS: Three patients sustained SCIs: two cervical spine (C4 AIS-A and C5 AIS-B) and one thoracolumbar junction fracture dislocation (T11 AIS-A). Two patients required surgical stabilization during pregnancy, with one undergoing surgery after delivery. All three patients subsequently delivered healthy newborns. The remaining two patients without neurologic deficits at admission were treated conservatively; one had a healthy child, whereas the other patient aborted the baby due to the initial trauma. CONCLUSIONS: Our study demonstrates that the same surgical principals may be applied to pregnant women as to routine patients with SCIs. Further studies with greater patient data should be performed to better develop significant guidelines for the management of pregnant patients with spinal injuries.

Perioperative Quality of Life in Cushing's Disease.

BACKGROUND: Our study evaluated the perioperative quality of life (QoL) in Cushing's disease (CD) patients, along with correlations between patient variables and cure rate. METHODS: The 36-item Short-Form Health Survey (SF)-36 questionnaire was used to assess perioperative QoL. Patients completed one survey preoperatively and two surveys postoperatively. Retrospective chart review was conducted to collect SF-36 data as well as examine variables including: age, hospital stay, size of tumour, pathological diagnosis, timing of cure, and complication rates. Statistical analysis was conducted on the scores reported by the SF-36, and were compared with the normal Canadian population values, and to a sample of QoL from nonfunctioning pituitary tumour patients. This project was approved by University of British Columbia Research Ethics Board #H15-01572. RESULTS: In general, CD patients have relatively poor QoL that does improve as expected when cured, but not quite to normal levels. Factors associated with cure included presence of macroadenoma, confirmatory pathology, and patient age. Postoperative timing of cure appears to affect the durability of cure, with an immediate cure having a higher durability rate than delayed cure. Most recurrences occurred within 10 months postoperatively. CONCLUSIONS: This review of the perioperative QoL in CD helps to illustrate how QoL changes throughout the treatment process, how QoL compares to normal Canadian population levels, and how QoL compares to patients with nonfunctioning pituitary adenomas. As treatment outcome has such a high impact on QoL, the variables identified in this study will help to better inform patients about the treatment course.