Unveiling the axonal connectivity between the precuneus and temporal pole: Structural evidence from the cingulum pathways.

Neuroimaging studies have consistently demonstrated concurrent activation of the human precuneus and temporal pole (TP), both during resting-state conditions and various higher-order cognitive functions. However, the precise underlying structural connectivity between these brain regions remains uncertain despite significant advancements in neuroscience research. In this study, we investigated the connectivity of the precuneus and TP by employing parcellation-based fiber micro-dissections in human brains and fiber tractography techniques in a sample of 1065 human subjects and a sample of 41 rhesus macaques. Our results demonstrate the connectivity between the posterior precuneus area POS2 and the areas 35, 36, and TG of the TP via the fifth subcomponent of the cingulum (CB-V) also known as parahippocampal cingulum. This finding contributes to our understanding of the connections within the posteromedial cortices, facilitating a more comprehensive integration of anatomy and function in both normal and pathological brain processes. PRACTITIONER POINTS: Our investigation delves into the intricate architecture and connectivity patterns of subregions within the precuneus and temporal pole, filling a crucial gap in our knowledge. We revealed a direct axonal connection between the posterior precuneus (POS2) and specific areas (35, 35, and TG) of the temporal pole. The direct connections are part of the CB-V pathway and exhibit a significant association with the cingulum, SRF, forceps major, and ILF. Population-based human tractography and rhesus macaque fiber tractography showed consistent results that support micro-dissection outcomes.

Alpha-Synuclein RT-QuIC in Idiopathic Normal Pressure Hydrocephalus.

This study quantified the occurrence of an underlying synucleinopathy in 50 patients with idiopathic normal pressure hydrocephalus by means of real-time quaking-induced conversion, a highly sensitive and specific technique capable of detecting and amplifying misfolded aggregated forms of α-synuclein in the cerebrospinal fluid. Seven patients were positive and they did not differ from negative cases, except for a more frequent L-dopa responsiveness and gait characterized by a wider base. The two groups did not differ in terms of response rate to tap test or shunt surgery, although step length and gait velocity improved by a lesser extent in positive cases. ANN NEUROL 2022;92:985-991.

Toxicity and outcomes of melanoma brain metastases treated with stereotactic radiosurgery: the risk of subsequent symptomatic intralesional hemorrhage exceeds that of radiation necrosis.

PURPOSE: We aimed to assess the outcomes and patterns of toxicity in patients with melanoma brain metastases (MBM) treated with stereotactic radiosurgery (SRS) with or without immunotherapy (IO). METHODS: From a prospective registry, we reviewed MBM patients treated with single fraction Gamma Knife SRS between 2008 and 2021 at our center. We recorded all systemic therapies (chemotherapy, targeted therapy, or immunotherapy) administered before, during, or after SRS. Patients with prior brain surgery were excluded. We captured adverse events following SRS, including intralesional hemorrhage (IH), radiation necrosis (RN) and local failure (LF), as well as extracranial disease status. Distant brain failure (DBF), extracranial progression-free survival (PFS) and overall survival (OS) were determined using a cumulative Incidence function and the Kaplan-Meier method. RESULTS: Our analysis included 165 patients with 570 SRS-treated MBM. Median OS for patients who received IO was 1.41 years versus 0.79 years in patients who did not (p = 0.04). Ipilimumab monotherapy was the most frequent IO regimen (30%). In the absence of IO, the cumulative incidence of symptomatic (grade 2 +) RN was 3% at 24 months and remained unchanged with respect to the type or timing of IO. The incidence of post-SRS g2 + IH in patients who did not receive systemic therapy was 19% at 1- and 2 years compared to 7% at 1- and 2 years among patients who did (HR: 0.33, 95% CI 0.11-0.98; p = 0.046). Overall, neither timing nor type of IO correlated to rates of DBF, OS, or LF. Among patients treated with IO, the median time to extracranial PFS was 5.4 months (95% IC 3.2 - 9.1). CONCLUSION: The risk of g2 + IH exceeds that of g2 + RN in MBM patients undergoing SRS, with or without IO. IH should be considered a critical adverse event following MBM treatments.

Anatomical and surgical characteristics correlate with pachymeningeal failure in patients with brain metastases after neurosurgical resection and adjuvant stereotactic radiosurgery.

PURPOSE: Neurosurgery (NS) is an essential modality for large brain metastases (BM). Postoperative stereotactic radiosurgery (SRS) is the standard of care adjuvant treatment. Pachymeningeal failure (PMF) is a newly described entity, distinct from classical leptomeningeal failure (LMF), that is uniquely observed in postoperative patients treated with adjuvant SRS. We sought to identify risk factors for PMF in patients treated with NS + SRS. METHODS: From a prospective registry (2009 to 2021), we identified all patients treated with NS + SRS. Clinical, imaging, pathological, and treatment factors were analyzed. PMF incidence was evaluated using a competing risks model. RESULTS: 144 Patients were identified. The median age was 62 (23-90). PMF occurred in 21.5% (31/144). Female gender [Hazard Ratio (HR) 2.65, p = 0.013], higher Graded Prognostic Assessment (GPA) index (HR 2.4, p < 0.001), absence of prior radiation therapy (HR N/A, p = 0.018), controlled extracranial disease (CED) (HR 3.46, p = 0.0038), and pia/dura contact (PDC) (HR 3.30, p = 0.0053) were associated with increased risk for PMF on univariate analysis. In patients with PDC, wider target volumes correlated with reduced risk of PMF. Multivariate analysis indicated PDC (HR 3.51, p = 0.0053), piecemeal resection (HR 2.38, p = 0.027), and CED (HR 3.97, p = 0.0016) independently correlated with PMF risk. PMF correlated with reduced OS (HR 2.90, p < 0.001) at a lower rate compared to LMF (HR 10.15, p < 0.001). CONCLUSION: PMF correlates with tumor PDC and piecemeal resection in patients treated with NS + SRS. For unclear reasons, it is also associated with CED. In tumors with PDC, wider dural radiotherapy coverage was associated with a lower risk of PMF.

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.

Subcortical language localization using sign language and awake craniotomy for dominant posterior temporal glioma resection in a hearing-impaired patient.

Intraoperative direct cortical stimulation (DCS) is the gold standard technique to maximize the extent of resection of tumors located in eloquent areas. To date, there are three cases reported of awake mapping for language centers in deaf patients who could communicate only with sign language. We present the case of DCS in a deaf patient who could communicate vocally, native to American Sign Language and English, that underwent intraoperative awake mapping. DCS showed similar disruption of expressive phonology to both pictorial and gestural stimuli, confirming that sign language follows the same pattern as oral language.

Postoperative CT scans after resection of brain metastases: neurosurgical routine or added value?

BACKGROUND: Metastasis is the most common brain tumor in adults. It is the standard of care at most North American centers to obtain an early postoperative imaging after their resection. However, the necessity of this practice in the absence of a new postoperative deficit remains unclear. METHODS: We retrospectively reviewed our surgical cohort of patients who underwent resection of brain metastases from July 2018 to June 2019. We collected demographic data and reviewed results of routine postoperative CT scans and neurological morbidities to examine the diagnostic and therapeutic yield of an early postoperative scan. In addition, we performed a systematic review of the topic. RESULTS: Our review included 130 patients, all of whom underwent gross total resection of one or more brain metastases. On postoperative CT, none had unexpected findings such as cavity hematoma or new ischemia; no changes in management resulted from postoperative imaging. One patient required a higher dose of dexamethasone on postoperative day 4 for delayed hemiparesis and aphasia due to cerebral edema. Three additional patients underwent a wound washout for delayed infection during a subsequent admission. Our systematic review identified three additional studies; in a combined cohort of 450 patients (including our own), no patients had clinically actionable findings on routine postoperative CT. CONCLUSIONS: Following resection of brain metastases, a routine postoperative CT scan has low diagnostic yield and did not change patient management in any cases examined in this work.

Long-term neurocognitive, psychological, and return to work outcomes in meningioma patients.

INTRODUCTION: This study aimed to investigate long-term neurocognitive, psychological, and return to work (RTW) outcomes in meningioma patients, and to explore whether neurocognitive and psychological factors influence RTW outcomes in this population. METHODS: In this retrospective study, 61 meningioma patients completed in-depth clinical neuropsychological assessments. Of these participants, 42 were of working-age and had RTW information available following neuropsychological assessment. Seventy-one percent and 80% of patients received radiation and surgery, respectively, with 49% receiving both radiation and surgery. Associations between demographic, medical, neurocognitive, psychological, and RTW data were analyzed using multivariable logistic regression analyses. RESULTS: In our sample, 68% of patients exhibited global neurocognitive impairment, with the largest effect sizes found on tests of visual memory (d = 0.73), executive function (d = 0.61), and attention (d = 0.54). Twenty-seven percent exhibited moderate to severe levels of depressive symptoms. In addition, 23% and 30% exhibited clinically significant state and trait anxiety, respectively. Forty-eight percent of patients were unable to RTW. Younger age, faster visuomotor processing speed, and, unexpectedly, higher trait anxiety scores were associated with an increased likelihood of returning to work. CONCLUSIONS: Meningioma patients are at risk of experiencing neurocognitive deficits, psychological symptoms, and difficulties returning to work. Our results suggest that neurocognitive and psychological factors contribute to RTW status in meningioma patients. Prospective research studies are necessary to increase our understanding of the complexity of functional disability in this growing population.

The centrally restricted diffusion sign on MRI for assessment of radiation necrosis in metastases treated with stereotactic radiosurgery.

PURPOSE: Differentiation of radiation necrosis from tumor progression in brain metastases treated with stereotactic radiosurgery (SRS) is challenging. For this, we assessed the performance of the centrally restricted diffusion sign. METHODS: Patients with brain metastases treated with SRS who underwent a subsequent intervention (biopsy/resection) for a ring-enhancing lesion on preoperative MRI between 2000 and 2020 were included. Excluded were lesions containing increased susceptibility limiting assessment of DWI. Two neuroradiologists classified the location of the diffusion restriction with respect to the post-contrast T1 images as centrally within the ring-enhancement (the centrally restricted diffusion sign), peripherally correlating to the rim of contrast enhancement, both locations, or none. Measures of diagnostic accuracy and 95% CI were calculated for the centrally restricted diffusion sign. Cohen's kappa was calculated to identify the interobserver agreement. RESULTS: Fifty-nine patients (36 female; mean age 59, range 40 to 80) were included, 36 with tumor progression and 23 with radiation necrosis based on histopathology. Primary tumors included 34 lung, 12 breast, 5 melanoma, 3 colorectal, 2 esophagus, 1 head and neck, 1 endometrium, and 1 thyroid. The centrally restricted diffusion sign was seen in 19/23 radiation necrosis cases (sensitivity 83% (95% CI 63 to 93%), specificity 64% (95% CI 48 to 78%), PPV 59% (95% CI 42 to 74%), NPV 85% (95% CI 68 to 94%)) and 13/36 tumor progression cases (difference p < 0.001). Interobserver agreement was substantial, at 0.61 (95% CI 0.45 to 70.8). CONCLUSION: We found a low probability of radiation necrosis in the absence of the centrally restricted diffusion sign.

Brain Metastases: A Modern Multidisciplinary Approach.

Brain metastases (BM) are the most common intracranial neoplasm and represent a major clinical challenge across many medical disciplines. The incidence of BM is increasing, largely due to improvements in primary disease therapeutics conferring greater systemic control, and advancements in neuroimaging techniques and availability leading to earlier diagnosis. In recent years, the landscape of BM treatment has changed significantly with the advent of personalized targeted chemotherapies and immunotherapy, the adoption of focal radiotherapy (RT) for higher intracranial disease burden, and the implementation of new surgical strategies. The increasing permutations of options available for the treatment of patients diagnosed with BM necessitate coordinated care by a multidisciplinary team. This review discusses the current treatment regimens for BM as well as examines the salient features of a modern multidisciplinary approach.

Hyperbaric Oxygen for Radiation Necrosis of the Brain.

INTRODUCTION: Hyperbaric oxygen therapy (HBOT) shows promising results in treating radionecrosis (RN) but there is limited evidence for its use in brain RN. The purpose of this study is to report the outcomes of using HBOT for symptomatic brain RN at a single institution. METHODS: This was a retrospective review of patients with symptomatic brain RN between 2008 and 2018 and was treated with HBOT. Demographic data, steroid use, clinical response, radiologic response and toxicities were collected. The index time for analysis was the first day of HBOT. The primary endpoint was clinical improvement of a presenting symptom, including steroid dose reduction. RESULTS: Thirteen patients who received HBOT for symptomatic RN were included. The median time from last brain radiation therapy to presenting symptoms of brain RN was 6 months. Twelve patients (92%) had clinical improvement with median time to symptom improvement of 33 days (range 1-109 days). One patient had transient improvement after HBOT but had recurrent symptomatic RN at 12 months. Of the eight patients with evaluable follow-up MRI, four patients had radiological improvement while four had stable necrosis appearance. Two patients had subsequent deterioration in MRI appearances, one each in the background of initial radiologic improvement and stability. Median survival was 15 months with median follow-up of 10 months. Seven patients reported side effects attributable to HBOT (54%), four of which were otologic in origin. CONCLUSIONS: HBOT is a safe and effective treatment for brain RN. HBOT showed clinical and radiologic improvement or stability in most patients. Prospective studies to further evaluate the effectiveness and side effects of HBOT are needed.

Utilisation de l'oxygénothérapie hyperbare à la suite de séances de radiothérapie entraînant la mort du tissu cérébral. Introduction: Si l'oxygénothérapie hyperbare (OHB) laisse entrevoir des résultats prometteurs dans le traitement des radionécroses (RN), les preuves demeurent limitées quant à son utilisation dans le cas de RN du cerveau. L'objectif de cette étude est de présenter des résultats de recherche liés, dans un seul établissement de santé, à l'utilisation de l'OHB dans le cas de RN symptomatiques du cerveau. Méthodes: Pour ce faire, nous avons effectué une analyse rétrospective des dossiers de patients atteints de RN symptomatiques du cerveau entre 2008 et 2018 et ayant été traités lors de séances d'OHB. Nous avons aussi recueilli des données de nature démographique et d'autres portant sur l'utilisation de stéroïdes, sur la réponse clinique et radiologique des patients et sur les toxicités. Le point de départ (index time) de notre étude a été la première séance d'OHB alors que son principal indicateur de résultat a été l'amélioration sur le plan clinique d'un symptôme particulier, ce qui a inclus une réduction des doses de stéroïdes. Résultats: Au total, treize patients atteints de RN symptomatiques ont été inclus dans cette étude. Le temps médian entre une ultime séance de radiothérapie et l'apparition de symptômes de RN a été de 6 mois. Douze patients (92 %) ont donné à voir une amélioration de leur état médical, la période médiane d'amélioration de leurs symptômes étant de 33 jours (étendue : 1­109 jours). On a observé chez un seul patient une amélioration transitoire à la suite de séances d'OHB, les symptômes de RN étant réapparus au douzième mois. Sur les huit patients ayant subi un examen d'imagerie de suivi, quatre d'entre eux ont montré des signes d'amélioration sur le plan radiologique tandis que quatre autres ont donné à voir une RN stable. Fait à noter, deux patients chez qui l'on avait observé une amélioration radiologique initiale ou une stabilité de leur état ont montré une détérioration ultérieure à la suite d'un examen d'IRM. Le taux de survie médian de ces patients et leur suivi médian ont été respectivement de 15 mois et de 10 mois. Enfin, sept d'entre eux ont signalé des effets secondaires attribuables à l'OHB, dont quatre d'origine otologique. Conclusions: L'OHB demeure un traitement efficace et sécuritaire dans le cas des RN du cerveau. Elle a permis d'observer chez la plupart des patients une amélioration clinique et radiologique ou à tout le moins une stabilité de leurs symptômes. Cela dit, des études prospectives sont nécessaires afin de pouvoir évaluer plus en profondeur son efficacité et ses effets secondaires.

Evidence of small-fiber neuropathy in neurofibromatosis type 1.

INTRODUCTION: Large-fiber neuropathy is rare in neurofibromatosis type 1, but small-fiber neuropathy has not been studied. METHODS: Patients with neurofibromatosis type 1 underwent nerve conduction studies for large-fiber assessment. Small-fiber tests included quantitative thermal thresholds, laser Doppler flare imaging, intraepidermal nerve fiber density, and corneal nerve fiber length. RESULTS: Of the 52 patients enrolled, 31 (60%) were female and the mean age was 33.0 ± 12.3 years. Four (8%) patients had abnormal nerve conduction studies. Small-fiber tests were frequently abnormal: thermal thresholds in 7 (13%); laser Doppler flare imaging in 10 (19%); intraepidermal nerve fiber density in 11 (22%); and corneal nerve fiber length in 27 (52%). The mean corneal nerve fiber length was below normative level (10.1 ± 2.7 mm/mm3 ). DISCUSSION: Small-fiber neuropathy may be common in neurofibromatosis type 1, and should be investigated in symptomatic patients.

5-Hydroxymethylcytosine preferentially targets genes upregulated in isocitrate dehydrogenase 1 mutant high-grade glioma.

Gliomas demonstrate epigenetic dysregulation exemplified by the Glioma CpG Island Methylator Phenotype (G-CIMP) seen in IDH1 mutant tumors. 5-Hydroxymethylcytosine (5hmC) is implicated in glioma pathogenesis; however, its role in IDH1 mutant gliomas is incompletely understood. To characterize 5hmC in IDH1 mutant gliomas further, we examine 5hmC in a cohort of IDH1 mutant and wild-type high-grade gliomas (HGG) using a quantitative locus-specific approach. Regions demonstrating high 5hmC abundance and differentially hydroxymethylated regions (DHMR) enrich for enhancers implicated in glioma pathogenesis. Among these regions, IDH1 mutant tumors possess greater 5hmC compared to wild type. 5hmC contributes to overall methylation status of G-CIMP genes. 5hmC targeting gene body regions correlates significantly with increased gene expression. In particular, a strong correlation between increased 5hmC and increased gene expression is identified for genes highly expressed in the IDH1 mutant cohort. Overall, locus-specific gain of 5hmC targeting regulatory regions and associated with overexpressed genes suggests a significant role for 5hmC in IDH1 mutant HGG.

The relationship of study and authorship characteristics on trial sponsorship and self-reported conflicts of interest among neuro-oncology clinical trials.

PROPOSE: To examine the association between trial sponsorship sources, self-reported conflicts of interest (COI), and study and author characteristics in central nervous system (CNS) oncology clinical trials (CT). METHODS: MEDLINE search was performed for original CT on "Central Nervous System Neoplasms"[Mesh]. The investigators assessed for relationships between funding source (industry, academic or cooperative, none, not described), COI (presented, none, or not reported), CT, and author characteristics. RESULTS: From 2010 to 2015, 319 CT were considered eligible. The majority of the studies involved primary gliomas (55.2%) and were Phase II CT (59.2%). Drug therapy was investigated in 83.0% of the CT. The remaining studies investigated surgery or radiotherapy. A minority of papers were published in journals with impact factor (IF) higher than > 10 (16%) or in regions other than North America and Europe (20.4%). Overall, 83.1% of studies disclosed funding sources: 32.6% from industry alone, 33.9% from an academic or cooperative group, and 10.7% from a mixed funding model. COI data was reported by 85.9% of trials, of which 56.2% reported no COI and 43.8% reported a related COI. Significant predictors for sponsorship (industry and/or academia) on univariate analysis were study design, type of intervention, journal impact factor, study conclusion, transparency of COI and presence of COI. On multivariate analysis, type of intervention, (P < 0.001), journal impact factor (IF) (P = 0.003), presence of COI (P < 0.001) and study conclusion (P = 0.003) remained significant predictors of sponsorship. For predicting COI, significant variables on univariate analysis were disease type, type of intervention, journal IF, funding source, and intervention arm being related to sponsor. On multivariate analysis, disease type (P = 0.003), journal IF (P < 0.001), type of intervention (P = 0.001), and funding source (P = 0.008) remained significant. CONCLUSIONS: The majority of CNS CT reported some external funding sources and non-related COI. We identified that drug trials, higher IF, presence of COI, and a neutral or negative study conclusion are associated with external funding. Likewise drug trials, higher IF, and glioma trials are associated with presence of COI.

Management and Outcomes in the Oldest-Old Population with Glioblastoma.

OBJECTIVES: Glioblastoma is a lethal disease in the elderly population. We aimed to evaluate disease and treatment outcomes in the oldest-old patients. METHODS: Patients >80 years old with histologically confirmed glioblastoma treated between 2004 and 2009 were identified. We included patients managed with best supportive care (BSC), temozolomide (TMZ) alone, radiotherapy (RT) alone, or concomitantly with TMZ (CRT). Survival outcomes were analyzed using the Kaplan-Meier method. RESULTS: Ultimately, 48 patients were analyzed. Median age and Eastern Cooperative Oncology Group (ECOG) Performance Status were 82 years and 2, respectively. The median Age-Adjusted Charlson Index (AAC) was 6. Gross total and subtotal resections were performed in 16.7% and 18.8% of patients, respectively. Biopsy followed by RT alone was the treatment modality for 23/48 (47.9%), while 17/48 (35.4%) received surgery followed by RT alone or CRT. A total of 8 (16.7%) were managed with BSC after biopsy. Median overall survival (OS) and progression-free survival (PFS) were 4.1 (95% confidence interval [95% CI] 3.3-4.9) and 2.7 (95% CI 1.5-3.9) months, respectively. Improved median OS was observed in those treated with surgical resection followed by RT alone or CRT (7.1 months), compared to biopsy followed by RT alone (4.2 months) or BSC (2.0 months; p=0.002). Surgical resection, age≤85, and AAC<6 were associated with better OS (p=0.032, p=0.031, and p=0.02, respectively). Cause of death was neurological progression in 56% of cases. RT was well-tolerated. CONCLUSIONS: PFS and OS outcomes remain poor in the oldest-old patients (>80 years old). Younger age, lower AAC, surgical resection, and adjuvant treatment were associated with improved OS.

Neurofibromatosis Clinic: A Report on Patient Demographics and Evaluation of the Clinic.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a common single-gene disorder. A multidisciplinary approach to the management of NF1 patients is necessitated by the heterogeneity of clinical manifestations. Although multidisciplinary paediatric clinics have been well established, there is a dearth of such resources for adults with NF1. Herein we report our one-year institutional experience with a multidisciplinary adult NF1 clinic. METHODS: A multidisciplinary team was assembled, and an NF Patient Registry Initiative questionnaire was adapted to collect patient-reported data during clinics. Multiple databases were searched to identify publications pertaining to the experience of other multidisciplinary NF1 clinics focusing on adult patients. Data on patient epidemiology and clinical staff were compared to our data. RESULTS: A total of 77 patients were scheduled, and 68 attended the clinic, of whom 66 completed the intake questionnaire. The demographic and clinical data from this Canadian population are mostly consistent with previous reports, with some exceptions. Clinical data related to immune system involvement such as asthma, airway/breathing-related difficulties or allergies were striking in our NF1 population. Six relevant published reports of other NF1 clinics were identified. Reports from these studies pertained to periods ranging from 10 to 38 months, and the number of adults assessed ranged from 19 to 177 patients. CONCLUSIONS: The structure of our clinic and the patient volume are comparable to those of other established centres found in the literature. Our data offer valuable cross-sectional prevalence statistics in the Canadian population. The patient-reported data concerning involvement of the immune system contribute to an emerging recognized medical concern within the NF1 population and warrant further clinical and basic investigation.

Neurosurgical management of adult diffuse low grade gliomas in Canada: a multi-center survey.

Adult diffuse low-grade gliomas are slow growing, World Health Organization grade II lesions with insidious onset and ultimate anaplastic transformation. The timing of surgery remains controversial with polarized practices continuing to govern patient management. As a result, the management of these patients is variable. The goal of this questionnaire was to evaluate practice patterns in Canada. An online invitation for a questionnaire including diagnostic, preoperative, perioperative, and postoperative parameters and three cases with magnetic resonance imaging data with questions to various treatment options in these patients was sent to practicing neurosurgeons and trainees. Survey was sent to 356 email addresses with 87 (24.7%) responses collected. The range of years of practice was less than 10 years 36% (n = 23), 11-20 years 28% (n = 18), over 21 years 37% (n = 24). Twenty-two neurosurgery students of various years of training completed the survey. 94% (n = 47) of surgeons and trainees (n = 20) believe that we do not know the "right treatment". 90% of surgeons do not obtain formal preoperative neurocognitive assessments. 21% (n = 13) of surgeons and 23% of trainees (n = 5) perform a biopsy upon first presentation. A gross total resection was believed to increase progression free survival (surgeons: 75%, n = 46; trainees: 95%, n = 21) and to increase overall survival (surgeons: 64%, n = 39, trainees: 68%, n = 15). Intraoperative MRI was only used by 8% of surgeons. Awake craniotomy was the procedure of choice for eloquent tumors by 80% (n = 48) of surgeons and 100% of trainees. Of those surgeons who perform awake craniotomy 93% perform cortical stimulation and 38% performed subcortical stimulation. Using the aid of three hypothetical cases with progressive complexities in tumor eloquence there was a trend for younger surgeons to operate earlier, and use awake craniotomy to obtain greater extent of resection with the aid of cortical stimulation when compared to senior surgeons who still more often preferred a "wait-and-see" approach. Despite the limitations of an online survey study, it has offered insights into the variability in surgeon practice patterns in Canada and the need for a consensus on the workup and surgical management of this disease.

Long-term neurocognitive and psychological outcomes in meningioma survivors: Individual changes over time and radiation dosimetry.

Background: This study investigates long-term changes in neurocognitive performance and psychological symptoms in meningioma survivors and associations with radiation dose to circumscribed brain regions. Methods: We undertook a retrospective study of meningioma survivors who underwent longitudinal clinical neurocognitive assessments. Change in neurocognitive performance or psychological symptoms was assessed using reliable change indices. Radiation dosimetry, if prescribed, was evaluated based on treatment-planning computerized tomography co-registered with contrast-enhanced 3D T1-weighted magnetic resonance imaging. Mixed effects analyses were used to explore whether incidental radiation to brain regions outside the tumor influences neurocognitive and psychological outcomes. Results: Most (range = 41%-93%) survivors demonstrated stable-albeit often below average-neurocognitive and psychological trajectories, although some also exhibited improvements (range = 0%-31%) or declines (range = 0%-36%) over time. Higher radiation dose to the parietal-occipital region (partial R2 = 0.462) and cerebellum (partial R2 = 0.276) was independently associated with slower visuomotor processing speed. Higher dose to the hippocampi was associated with increases in depression (partial R2 = 0.367) and trait anxiety (partial R2 = 0.236). Conclusions: Meningioma survivors experience neurocognitive deficits and psychological symptoms many years after diagnosis, and a proportion of them decline over time. This study offers proof of concept that incidental radiation to brain regions beyond the tumor site may contribute to these sequelae. Future investigations should include radiation dosimetry when examining risk factors that contribute to the quality of survivorship in this growing population.

Rate of pachymeningeal failure following adjuvant WBRT vs SRS in patients with brain metastases.

Background: Stereotactic radiosurgery (SRS) has supplanted whole brain radiotherapy (WBRT) as standard-of-care adjuvant treatment following surgery for brain metastasis (BrM). Concomitant with the adoption of adjuvant SRS, a new pattern of failure termed "Pachymeningeal failure" (PMF) has emerged. Methods: We reviewed a prospective registry of 264 BrM patients; 145 and 119 were treated adjuvantly with WBRT and SRS, respectively. The Cox proportional hazards model was used to identify variables correlating to outcomes. Outcomes were calculated using the cumulative incidence (CI) method. Univariate (UVA) and multivariate analyses (MVA) were done to identify factors associated with PMF. Results: CI of PMF was 2 % and 18 % at 12 months, and 2 % and 23 % at 24 months for WRBT and SRS, respectively (p < 0.001). The CI of classic leptomeningeal disease (LMD) was 3 % and 4 % at 12 months, and 6 % and 6 % at 24 months for WBRT and SRS, respectively (P = 0.67). On UVA, adjuvant SRS [HR 9.75 (3.43-27.68) (P < 0.001)]; preoperative dural contact (PDC) [HR 6.78 (1.64-28.10) (P = 0.008)]; GPA score [HR 1.64 (1.11-2.42) (P = 0.012)]; and lung EGFR/ALK status [HR 3.11 (1.02-9.45) (P = 0.045)]; were associated with PMF risk. On MVA, adjuvant SRS [HR 8.15 (2.69-24.7) (P < 0.001)]; and PDC [HR 6.28 (1.51-26.1) (P = 0.012)] remained associated with PMF. Conclusions: Preoperative dural contact and adjuvant SRS instead of adjuvant WBRT were associated with an increased risk of PMF. Strategies to improve pachymeningeal radiation coverage to sterilize at risk pachymeninges should be investigated.

LITTing up Gliomas-Is the Future Bright?

Background: Laser interstitial thermal therapy (LITT) represents an attractive therapeutic strategy for several intracranial pathologies; however, there is a paucity of literature regarding its efficacy for the treatment of gliomas. Methods: MEDLINE, EMBASE, Scopus, and Web of Science were searched from inception until March 19, 2021. Studies specifically relating to the use of LITT in treatment of glioma were eligible for inclusion. A meta-analysis of means was performed to assess the progression-free survival (PFS) and overall survival (OS) following LITT and descriptive statistics relating to patients undergoing LITT were collated and a meta-analysis of proportions was also performed to assess the rate of complications. Results: In total, 17 studies were included for the meta-analysis, comprising 401 patients with 408 gliomas of which 88 of 306 (28.8%) were grade 1 or 2 and 218 of 306 (71.2%) were grade 3 or 4. Of these, 256 of 408 (62.8%) were primary presentation and 152 of 408 (37.2%) were recurrent. The pooled mean OS was 13.58 months (95% confidence interval [CI] 9.77-17.39) and the PFS was 4.96 months (95% CI 4.19-5.72). The OS and PFS of recurrent glioblastoma were 12.4 months (95% CI 9.61-16.18) and 4.84 months (95% CI 0.23-9.45), respectively. Complications occurred in 114 of 411 (24%; 95% CI 14-41), of which 44 (11%) were transient deficits. Conclusions: There is an increasing body of evidence demonstrating the use of LITT in the surgical management of deep-seated gliomas in patients of poor performance status. However, further studies are required to interrogate the clinical effectiveness of LITT in the setting of gliomas as well as assessing the survival benefit versus standard treatment alone.