Bilingual awake craniotomy with English and Polish language mapping in a 15-year-old patient provides evidence for the role of the left superior temporal gyrus in language switching.

The utility of intraoperative mapping in multilingual patients with brain tumours in speech-eloquent locations is evidenced by reports of heterogeneity of the location and number of language areas. Furthermore, preserving the ability to switch between languages is crucial for multilingual patients' communication and quality of life. We report the first case of intraoperative bilingual and language switching testing in a child undergoing awake craniotomy for a tumour within the left superior temporal gyrus using a novel test paradigm.

Awake craniotomy with English and British sign language mapping in a patient with a left temporal glioblastoma reveals discordant speech-sign language maps.

The aim of this case study was to describe differences in English and British Sign Language (BSL) communication caused by a left temporal tumour resulting in discordant presentation of symptoms, intraoperative stimulation mapping during awake craniotomy and post-operative language abilities. We report the first case of a hearing child of deaf adults, who acquired BSL with English as a second language. The patient presented with English word finding difficulty, phonemic paraphasias, and reading and writing challenges, with BSL preserved.

Non-pharmacological fatigue interventions for patients with a primary brain tumour: a scoping review protocol.

Introduction: Fatigue is the most prevalent symptom for patients with a primary brain tumour (PBT), significantly reducing quality of life and limiting daily activities. Currently, there are limited options for managing cancer-related fatigue (CRF) in patients with a PBT, using non-pharmacological methods. The objective of this scoping review is to identify current and emerging evidence in relation to non-pharmacological CRF interventions for patients with a PBT.

Theory-based implementation of an enhanced recovery protocol for cranial surgery.

Objective: There is growing evidence for the use of enhanced recovery protocols (ERPs) in cranial surgery. As they become widespread, successful implementation of these complex interventions will become a challenge for neurosurgical teams owing to the need for multidisciplinary engagement. Here, the authors describe the novel use of an implementation framework (normalization process theory [NPT]) to promote the incorporation of a cranial surgery ERP into routine neuro-oncology practice.

Usability of mixed reality in awake craniotomy planning.

Purpose: This study aimed to describe our institutional use of a commercially available mixed reality viewer within a multi-disciplinary planning workflow for awake craniotomy surgery and to report an assessment of its usability.

Materials And Methods: Three Tesla MRI scans, including 32-direction diffusion tensor sequences, were reconstructed with BrainLab Elements auto-segmentation software. Magic Leap mixed reality viewer headsets were registered to a shared virtual viewing space to display image reconstructions.

Clinical Outcome of "Asleep" Deep Brain Stimulation for Parkinson Disease Using Robot-Assisted Delivery and Anatomic Targeting of the Subthalamic Nucleus: A Series of 152 Patients.

Background: Recent advances in methods used for deep brain stimulation (DBS) include subthalamic nucleus electrode implantation in the "asleep" patient without the traditional use of microelectrode recordings or intraoperative test stimulation.

Objective: To examine the clinical outcome of patients who have undergone "asleep" DBS for the treatment of Parkinson disease using robot-assisted electrode delivery.

Methods: This is a retrospective review of clinical outcomes of 152 consecutive patients.

Impact of COVID-19 pandemic on surgical neuro-oncology multi-disciplinary team decision making: a national survey (COVID-CNSMDT Study).

Objectives: Pressures on healthcare systems due to COVID-19 has impacted patients without COVID-19 with surgery disproportionally affected. This study aims to understand the impact on the initial management of patients with brain tumours by measuring changes to normal multidisciplinary team (MDT) decision making.

Design: A prospective survey performed in UK neurosurgical units performed from 23 March 2020 until 24 April 2020.

Two Hundred Twenty-Six Consecutive Deep Brain Stimulation Electrodes Placed Using an "Asleep" Technique and the Neuro|MateTM Robot for the Treatment of Movement Disorders.

Background: Robotics in neurosurgery has demonstrated widening indications and rapid growth in recent years. Robotic precision and reproducibility are especially pertinent to the field of functional neurosurgery. Deep brain stimulation (DBS) requires accurate placement of electrodes in order to maximize efficacy and minimize side effects.

Deep brain stimulation: practical insights and common queries.

The number of patients with deep brain stimulation (DBS) devices implanted is increasing. Although practices vary between centres, patients are typically given training and information from their DBS nurse or clinician, as well as a comprehensive device manual and contact details for their device manufacturer. However, for the lifetime of a patient with a DBS system, most of their secondary care often occurs in a centre without a co-located DBS service.

Extended Treatment with Glial Cell Line-Derived Neurotrophic Factor in Parkinson's Disease.

Background: Intraputamenal glial cell line-derived neurotrophic factor (GDNF), administered every 4 weeks to patients with moderately advanced Parkinson's disease, did not show significant clinical improvements against placebo at 40 weeks, although it significantly increased [18F]DOPA uptake throughout the entire putamen.

Objective: This open-label extension study explored the effects of continued (prior GDNF patients) or new (prior placebo patients) exposure to GDNF for another 40 weeks.

Methods: Using the infusion protocol of the parent study, all patients received GDNF without disclosing prior treatment allocations (GDNF or placebo).

Randomized trial of intermittent intraputamenal glial cell line-derived neurotrophic factor in Parkinson's disease.

We investigated the effects of glial cell line-derived neurotrophic factor (GDNF) in Parkinson's disease, using intermittent intraputamenal convection-enhanced delivery via a skull-mounted transcutaneous port as a novel administration paradigm to potentially afford putamen-wide therapeutic delivery. This was a single-centre, randomized, double-blind, placebo-controlled trial. Patients were 35-75 years old, had motor symptoms for 5 or more years, and presented with moderate disease severity in the OFF state [Hoehn and Yahr stage 2-3 and Unified Parkinson's Disease Rating Scale motor score (part III) (UPDRS-III) between 25 and 45] and motor fluctuations.

Combined use of CDK4/6 and mTOR inhibitors induce synergistic growth arrest of diffuse intrinsic pontine glioma cells via mutual downregulation of mTORC1 activity.

Background: Diffuse intrinsic pontine glioma (DIPG) is a lethal type of pediatric brain tumor that is resistant to conventional chemotherapies. Palbociclib is a putative novel DIPG treatment that restricts the proliferation of rapidly dividing cancer cells via selective inhibition of cyclin-dependent kinase (CDK) 4 and CDK6. However, implementing palbociclib as a monotherapy for DIPG is unfeasible, as CDK4/6 inhibitor resistance is commonplace and palbociclib does not readily cross the blood-brain barrier (BBB) or persist in the central nervous system.

Maximising coverage of brain structures using controlled reflux, convection-enhanced delivery and the recessed step catheter.

Background: The design and use of convection-enhanced delivery catheters remains an active field as clinical trials have highlighted suboptimal distribution as a contributory factor to the failure of those studies. Recent studies indicate limitations and challenges in achieving target coverage using conventional point source delivery.

New Method: The recessed step catheter(RSC), developed by this group, does not function as a point source delivery device, but instead uses 'controlled reflux' of the infusate to a flow inhibiting recess feature.

Drug Delivery for Movement Disorders.

There has been substantial research interest in delivering therapeutic neurotrophic factors directly to the brain for the treatment of Parkinson's Disease (PD) and other movement disorders. Direct infusion of glial cell-line derived neurotrophic factor has been investigated in both pre-clinical models and clinical trials. In this chapter we discuss past and present research investigating the potential of direct drug delivery to the brain for the treatment of PD and other movement disorders.

Repurposing the anti-epileptic drug sodium valproate as an adjuvant treatment for diffuse intrinsic pontine glioma.

Targeting epigenetic changes in diffuse intrinsic pontine glioma (DIPG) may provide a novel treatment option for patients. This report demonstrates that sodium valproate, a histone deacetylase inhibitor (HDACi), can increase the cytotoxicity of carboplatin in an additive and synergistic manner in DIPG cells in vitro. Sodium valproate causes a dose-dependent decrease in DIPG cell viability in three independent ex vivo cell lines.

Single Electrode Deep Brain Stimulation with Dual Targeting at Dual Frequency for the Treatment of Chronic Pain: A Case Series and Review of the Literature.

Deep Brain Stimulation (DBS) has been used to target many deep brain structures for the treatment of chronic pain. The periaqueductal grey and periventricular grey (PAG/PVG) is an effective target but results are variable, sometimes short-lived or subject to tolerance. The centromedian intra-laminar parafascicular complex (CMPf) modulates medial pain pathways and CMPf DBS may address the affective aspects of pain perception.

Chronic, intermittent convection-enhanced delivery devices.

Background: Intraparenchymal convection-enhanced delivery (CED) of therapeutics directly into the brain has long been endorsed as a medium through which meaningful concentrations of drug can be administered to patients, bypassing the blood brain barrier. The translation of the technology to clinic has been hindered by poor distribution not previously observed in smaller pre-clinical models. In part this was due to the larger volumes of target structures found in humans but principally the poor outcome was linked to reflux (backflow) of infusate proximally along the catheter track.

Convection-Enhanced Delivery of Carboplatin PLGA Nanoparticles for the Treatment of Glioblastoma.

We currently use Convection-Enhanced Delivery (CED) of the platinum-based drug, carboplatin as a novel treatment strategy for high grade glioblastoma in adults and children. Although initial results show promise, carboplatin is not specifically toxic to tumour cells and has been associated with neurotoxicity at high infused concentrations in pre-clinical studies. Our treatment strategy requires intermittent infusions due to rapid clearance of carboplatin from the brain.

A novel implantable catheter system with transcutaneous port for intermittent convection-enhanced delivery of carboplatin for recurrent glioblastoma.

Context: Inadequate penetration of the blood-brain barrier (BBB) by systemically administered chemotherapies including carboplatin is implicated in their failure to improve prognosis for patients with glioblastoma. Convection-enhanced delivery (CED) of carboplatin has the potential to improve outcomes by facilitating bypass of the BBB.

Objective: We report the first use of an implantable CED system incorporating a novel transcutaneous bone-anchored port (TBAP) for intermittent CED of carboplatin in a patient with recurrent glioblastoma.

Preclinical evaluation of an O(6)-methylguanine-DNA methyltransferase-siRNA/liposome complex administered by convection-enhanced delivery to rat and porcine brains.

The main determinant of glioblastoma (GBM) resistance to temozolomide (TMZ) is thought to be O(6)-methylguanine-DNA methyltransferase (MGMT), which is a DNA-repair enzyme that removes alkyl groups from the O(6)-position of guanine. Previously, we reported that a MGMT-siRNA/cationic liposome complex exerted a clear synergistic antitumor effect in combination with TMZ. Translation to a clinical setting might be desirable for reinforcing the efficacy of TMZ therapy for GBM.

Convection-enhanced drug delivery to the brain: therapeutic potential and neuropathological considerations.

Convection-enhanced delivery (CED) describes a direct method of drug delivery to the brain through intraparenchymal microcatheters. By establishing a pressure gradient at the tip of the infusion catheter in order to exploit bulk flow through the interstitial spaces of the brain, CED offers a number of advantages over conventional drug delivery methods-bypass of the blood-brain barrier, targeted distribution through large brain volumes and minimization of systemic side effects. Despite showing early promise, CED is yet to fulfill its potential as a mainstream strategy for the treatment of neurological disease.

Clearance and toxicity of recombinant methionyl human glial cell line-derived neurotrophic factor (r-metHu GDNF) following acute convection-enhanced delivery into the striatum.

Background: Despite promising early results, clinical trials involving the continuous delivery of recombinant methionyl human glial cell line-derived neurotrophic factor (r-metHuGDNF) into the putamen for the treatment of Parkinson's disease have shown evidence of poor distribution and toxicity due to point-source accumulation. Convection-enhanced delivery (CED) has the potential to facilitate more widespread and clinically effective drug distribution.

Aims: We investigated acute CED of r-metHuGDNF into the striatum of normal rats in order to assess tissue clearance, toxicity (neuron loss, gliosis, microglial activation, and decreases in synaptophysin), synaptogenesis and neurite-outgrowth.

GDNF, NGF and BDNF as therapeutic options for neurodegeneration.

Glial cell-derived neurotrophic factor (GDNF), and the neurotrophin nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are important for the survival, maintenance and regeneration of specific neuronal populations in the adult brain. Depletion of these neurotrophic factors has been linked with disease pathology and symptoms, and replacement strategies are considered as potential therapeutics for neurodegenerative diseases such as Parkinson's, Alzheimer's and Huntington's diseases. GDNF administration has recently been shown to be an effective treatment for Parkinson's disease, with clinical trials currently in progress.

Anaesthetic complications in pigs undergoing MRI guided convection enhanced drug delivery to the brain: a case series.

Observations: A total of 13 intracerebral infusions were performed at approximately 1 month intervals in three NIH miniature pigs over the age range of 31-59 weeks. Pigs received azaperone and ketamine premedication to allow venous cannulation and propofol induction of anaesthesia. Anaesthesia was maintained with isoflurane throughout cranial surgery and MRI scanning.