A common tumour in a rare location: a single centre case series of cerebellar glioblastoma.

Although glioblastoma is the commonest primary brain tumour in adults, its location in the cerebellum is extremely rare. We present thirteen cases (3 female, 10 male; median age at presentation 56 [age range 21-77]) of surgically managed, histologically confirmed, primary cerebellar glioblastoma (cGB) over a 17 year period (2005-2022). Pre-operative radiological diagnosis was challenging given cGB rarity, although MRI demonstrated ring enhancement in all cases. Surgical management included posterior fossa craniectomy and debulking in 11 cases and burr hole biopsy in two. CSF diversion was necessary in four cases. No evidence of IDH or ATRX gene mutations was found when tested. Survival ranged from 1 to 22 months after diagnosis (mean 10.9 months). We also seek to understand why glioblastoma is rare in this location and discuss potential reasons for this. We hypothesise that increasing anatomical distance from germinal regions and decreased local endogenous neural stem cell activity (which has been associated with glioblastoma) may explain why glioblastoma is rare in the cerebellum. We hereby seek to add to the limited literature on cGB as this is the largest UK cGB series to date.

The effect of COVID-19 on pain control in patients with a neurostimulator in situ- a retrospective study.

BACKGROUND: De-novo chronic neuropathic pain following COVID-19 is widely recognised. However, there are currently no published studies investigating the effect of SARS-CoV-2 infection on patients with pre-existing neuropathic pain who have required spinal cord stimulator (SCS) implantation. Here, the authors aimed to analyse outcomes in their institution's patients who had spinal cord stimulator (SCS) implantation or revision procedures to the system over a 5-year period. Specifically, the short-term and long-term outcomes of patients who contracted COVID-19 during the follow-up period were compared to the control group of patients who did not. METHOD: Patients included in this study had spinal cord stimulator implantation (de-novo and revision procedures) between 1 January 2017 and 31 January 2022, for neuropathic pain of any aetiology. Patients deemed eligible for the study were invited to participate in a telephone survey through which clinical outcome data were collected. Pain scores were assessed with a modified form of the Brief Pain Inventory (BPI). RESULTS: Of 91 patients, 48 (52.7%) had contracted COVID-19 by the time of the survey. Patients who contracted COVID-19 had significantly worse BPI scores in the 'Least pain' domain following their infection and at time of the survey, when compared to their score 6 months after the operation. 22.9% (n = 11) of the patients who contracted COVID-19 experienced a change in their symptoms following their infection. Within this sub-group, there was a statistically significant deterioration in BPI scores in 10/11 domains following their infection and in 2/11 domains at time of the survey. Worsening severity of COVID-19 symptoms was not associated with worse BPI scores. CONCLUSIONS: Infection with SARS-CoV-2, in a significant proportion of patients with an SCS in situ, causes at least a transient deterioration in pain control. Further prospective multicentre studies are indicated to establish the prevalence of this phenomenon.

Surgery for Malignant Acute Ischemic Stroke: A Narrative Review of the Knowns and Unknowns.

Malignant acute ischemic stroke (AIS) is characterized by acute neurological deterioration caused by progressive space-occupying brain edema, often occurring in the first hours to days after symptom onset. Without any treatment, the result is often fatal. Despite advances in treatment for AIS, up to 80% of patients with a large hemispheric stroke or cerebellar stroke are at risk of poor outcome. Decompressive surgery can be life-saving in a subgroup of patients with malignant AIS, but uncertainties exist on patient selection, predictors of malignant infarction, perioperative management, and timing of intervention. Although survivors are left disabled, most agree with the original decision to undergo surgery and would make the same decision again. In this narrative review, we focus on the clinical and radiological predictors of malignant infarction in AIS and outline the technical aspects of decompressive surgery as well as duraplasty and cranioplasty. We discuss the current evidence and recommendations for surgery in AIS, highlighting gaps in knowledge, and suggest directions for future studies. KEY POINTS: · Acute ischemic stroke from occlusion of a proximal intracranial artery can progress quickly to malignant edema, which can be fatal in 80% of patients despite medical management.. · Decompression surgery is life-saving within 48 hours of stroke onset, but the benefits beyond this time and in the elderly are unknown.. · Decompressive surgery is associated with high morbidity, particularly in the elderly. The decision to operate must be made after considering the individual's preference and expectations of quality of life in the context of the clinical condition.. · Further studies are needed to refine surgical technique including value of duraplasty and understand the role monitoring intracranial pressure during and after decompressive surgery.. · More studies are needed on the pathophysiology of malignant cerebral edema, prediction models including imaging and biomarkers to identify which subgroup of patients will benefit from decompressive surgery.. · More research is needed on factors associated with morbidity and mortality after cranioplasty, safety and efficacy of implants, and comparisons between them.. · Further studies are needed to assess the long-term effects of physical disability and quality of life of survivors after surgery, particularly those with severe neurological deficits..

A Reappraisal of the Pathophysiology of Cushing Ulcer: A Narrative Review.

In 1932, Harvey Cushing described peptic ulceration secondary to raised intracranial pressure and attributed this to vagal overactivity, causing excess gastric acid secretion. Cushing ulcer remains a cause of morbidity in patients, albeit one that is preventable. This narrative review evaluates the evidence pertaining to the pathophysiology of neurogenic peptic ulceration. Review of the literature suggests that the pathophysiology of Cushing ulcer may extend beyond vagal mechanisms for several reasons: (1) clinical and experimental studies have shown only a modest increase in gastric acid secretion in head-injured patients; (2) increased vagal tone is found in only a minority of cases of intracranial hypertension, most of which are related to catastrophic, nonsurvivable brain injury; (3) direct stimulation of the vagus nerve does not cause peptic ulceration, and; (4) Cushing ulcer can occur after acute ischemic stroke, but only a minority of strokes are associated with raised intracranial pressure and/or increased vagal tone. The 2005 Nobel Prize in Medicine honored the discovery that bacteria play key roles in the pathogenesis of peptic ulcer disease. Brain injury results in widespread changes in the gut microbiome in addition to gastrointestinal inflammation, including systemic upregulation of proinflammatory cytokines. Alternations in the gut microbiome in patients with severe traumatic brain injury include colonization with commensal flora associated with peptic ulceration. The brain-gut-microbiome axis integrates the central nervous system, the enteric nervous system, and the immune system. Following the review of the literature, we propose a novel hypothesis that neurogenic peptic ulcer may be associated with alterations in the gut microbiome, resulting in gastrointestinal inflammation leading to ulceration.

Genome-Wide Expression and Anti-Proliferative Effects of Electric Field Therapy on Pediatric and Adult Brain Tumors.

The lack of treatment options for high-grade brain tumors has led to searches for alternative therapeutic modalities. Electrical field therapy is one such area. The Optune™ system is an FDA-approved novel device that delivers continuous alternating electric fields (tumor treating fields-TTFields) to the patient for the treatment of primary and recurrent Glioblastoma multiforme (GBM). Various mechanisms have been proposed to explain the effects of TTFields and other electrical therapies. Here, we present the first study of genome-wide expression of electrotherapy (delivered via TTFields or Deep Brain Stimulation (DBS)) on brain tumor cell lines. The effects of electric fields were assessed through gene expression arrays and combinational effects with chemotherapies. We observed that both DBS and TTFields significantly affected brain tumor cell line viability, with DBS promoting G0-phase accumulation and TTFields promoting G2-phase accumulation. Both treatments may be used to augment the efficacy of chemotherapy in vitro. Genome-wide expression assessment demonstrated significant overlap between the different electrical treatments, suggesting novel interactions with mitochondrial functioning and promoting endoplasmic reticulum stress. We demonstrate the in vitro efficacy of electric fields against adult and pediatric high-grade brain tumors and elucidate potential mechanisms of action for future study.

Dissection using pulsed radiofrequency energy device (PlasmaBlade) is safe and efficient in experimental revision neuromodulation implant surgery.

BACKGROUND: The use of functional neurosurgical implants has increased over the past 10 years. PlasmaBlade is an innovative electrosurgical appliance harnessing pulsed radiofrequency (RF) energy. Our aim was to assess the risk of damage to neuromodulation hardware during PlasmaBlade dissection. MATERIALS AND METHODS: A simulated setting with chicken breast threaded with different hardware and PlasmaBlade used in three configurations. . Post dissection, the wires were inspected naked eye and under an operating microscope. The induced current was assessed contemporaneously using an oscilloscope. RESULTS: Five surgeons tested the PlasmaBlade at different generator settings. Sixty dissections were undertaken. No structural damage or induced current was identified at CUT 3/4, COAG 5. At CUT 6, COAG 5 and during dissection in a perpendicular orientation with prolonged hardware contact, opacification of insulation material occurred in 15/20 dissections. There was no dissolution of insulation even at this setting. On deviation from Medtronic advice, hardware damaged occurred if one was reckless with the PlasmaBlade. CONCLUSION: When using the recommended settings and operational technique, PlasmaBlade dissection did not cause any damage to implant wiring/tubing in this simulated setting. This report seeks to add to clinical data suggesting PlasmaBlade is safe for dissection around deep brain stimulator (DBS), vagal nerve stimulator (VNS), and spinal cord stimulator (SCS) hardware.

Ion Channels as Therapeutic Targets in High Grade Gliomas.

Glioblastoma multiforme (GBM) is a lethal brain cancer with an average survival of 14-15 months even with exhaustive treatment. High grade gliomas (HGG) represent the leading cause of CNS cancer-related death in children and adults due to the aggressive nature of the tumour and limited treatment options. The scarcity of treatment available for GBM has opened the field to new modalities such as electrotherapy. Previous studies have identified the clinical benefit of electrotherapy in combination with chemotherapeutics, however the mechanistic action is unclear. Increasing evidence indicates that not only are ion channels key in regulating electrical signaling and membrane potential of excitable cells, they perform a crucial role in the development and neoplastic progression of brain tumours. Unlike other tissue types, neural tissue is intrinsically electrically active and reliant on ion channels and their function. Ion channels are essential in cell cycle control, invasion and migration of cancer cells and therefore present as valuable therapeutic targets. This review aims to discuss the role that ion channels hold in gliomagenesis and whether we can target and exploit these channels to provide new therapeutic targets and whether ion channels hold the mechanistic key to the newfound success of electrotherapies.

Multicolumn spinal cord stimulation for predominant back pain in failed back surgery syndrome patients: a multicenter randomized controlled trial.

Despite optimal medical management (OMM), low back pain (LBP) can be disabling, particularly after spinal surgery. Spinal cord stimulation (SCS) is effective in reducing neuropathic leg pain; however, evidence is limited for LBP. This prospective, open-label, parallel-group trial randomized (1:1) failed back surgery syndrome (FBSS) patients with predominant LBP to SCS plus OMM (SCS group) or OMM alone (OMM group) at 28 sites in Europe and the Americas. If trial stimulation was successful, a multicolumn SCS system was implanted. Outcomes were assessed at baseline (before randomization) and at 1, 3, 6, and 12 months after randomization. Patients could change treatment groups at 6 months. The primary outcome was the proportion of patients with ≥50% reduction in LBP (responder) at 6 months. Secondary outcomes included change in pain intensity, functional disability, and health-related quality of life (HRQoL). The results are posted at ClinicalTrials.gov under registration number NCT01697358. In the intent-to-treat analysis, there were more responders in the SCS group than in the OMM group (13.6%, 15/110 vs 4.6%, 5/108, difference 9% with 95% confidence interval 0.6%-17.5%, P = 0.036) at 6 months. The SCS group improved in all secondary outcomes compared with the OMM group. The OMM group only improved in HRQoL. In the SCS group, 17.6% (18/102) experienced SCS-related adverse events through 6 months, with 11.8% (12/102) requiring surgical reintervention. Adding multicolumn SCS to OMM improved pain relief, HRQoL, and function in a traditionally difficult-to-treat population of failed back surgery syndrome patients with predominant LBP. Improvements were sustained at 12 and 24 months.

Tumour treating fields in a combinational therapeutic approach.

The standard of care for patients with newly diagnosed Glioblastoma multiforme (GBM) has remained unchanged since 2005, with patients undergoing maximal surgical resection, followed by radiotherapy plus concomitant and maintenance Temozolomide. More recently, Tumour treating fields (TTFields) therapy has become FDA approved for adult recurrent and adult newly-diagnosed GBM following the EF-11 and EF-14 trials, respectively. TTFields is a non-invasive anticancer treatment which utilizes medium frequency alternating electric fields to target actively dividing cancerous cells. TTFields selectively targets cells within mitosis through interacting with key mitotic proteins to cause mitotic arrest and cell death. TTFields therapy presents itself as a candidate for the combinational therapy route due to the lack of overlapping toxicities associated with electric fields. Here we review current literature pertaining to TTFields in combination with alkylating agents, radiation, anti-angiogenics, mitotic inhibitors, immunotherapies, and also with novel agents. This review highlights the observed synergistic and additive effects of combining TTFields with various other therapies, as well highlighting the strategies relating to combinations with electric fields.

Hydrocephalus and trigeminal neuralgia: exploring the association and management options.

We report the successful surgical management of three patients with trigeminal neuralgia and hydrocephalus. MRI revealed no neurovascular contact at the trigeminal root entry zone. Trigeminal neuralgic symptoms were controlled following alleviation of hydrocephalus. We hypothesize that trigeminal nerve traction, secondary to hydrocephalus, as the cause for their trigeminal neuralgia.

Does trajectory matter? A study looking into the relationship of trajectory with target engagement and error accommodation in subthalamic nucleus deep brain stimulation.

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is now a key treatment choice for advanced Parkinson's disease. The optimum target area within the STN is well established. However, no emphasis on the impact of trajectory exists. The ellipsoid shape of the STN and the off-centre traditional target point mean that variation in the electrode inclination should affect STN engagement. Understanding of this relationship could inform trajectory selection during planning by improving STN engagements and margins for error. METHOD: We simulated electrode placement at the clinical target through a set of trial trajectories. Twelve three-dimensionally reconstructed STNs were created from magnetic resonance imaging data of six patients. An appropriate target within each STN was then chosen. Each STN was approached through 56 simulated trajectories arranged in a grid covering a quadrant of skull around and in front of the coronal suture. A subset of 20 viable trajectories was reassessed for depth of engagement in each STN whilst approaching the chosen target. RESULTS: Group averages for each trajectory are presented as traffic light maps and as an overlaid skull mask illustrating recommended electrode entry sites. Trajectories under 30 degrees anterior to the bregma and between 10 to 30 degrees off the midline accommodated over 2.4 degrees of wobble. A mean engagement of 6 mm was possible in half of the subset. The longest engagements are on trajectories which saddle the coronal suture, extending to 40 degrees lateral. Microelectrode tracts of 14 additional STNs were collated using the above protocol and engagement exceeded 5 mm in all central trajectories without capsular side effects, suggesting placement away from STN borders. CONCLUSIONS: Trajectory selection influences engagement and flexibility to accommodate electrode wobble or brain shift whilst approaching a chosen STN target. We recommend having the first trial trajectory 20 degrees anterior to the bregma, moving postero-laterally in successive trials to balance both error and engagement. When wider margins for error are beneficial (e.g. second side during bilateral procedures), trajectories nearer the coronal suture and around 25 degrees off the midline are advised.

The Nottingham Expectation and Complication score following Surgery (NECS): an universal scale for surgical outcome audit and peer comparison.

BACKGROUND: Consultant Outcomes Publication (COP) is an NHS England initiative for promoting improvements in quality of care. However, at present outcomes are commonly expressed as mortality rates which do not necessarily reflect the performance of surgeons. We developed the Nottingham Expectation and Complication score following Surgery (NECS) to determine the success of surgical treatment from both the clinical perspective and the practical expectations agreed between surgeons and patients during the consent process. METHOD: This was a pilot study to trial the use of the NECS score. It is a simple expression of overall outcome comprising three clinical domains: S - surgical outcome, T - surgical/technical complications and M - medical complications recorded by the treating clinician, and practical outcome determined by a joint clinical/patient assessment. 107 elective neurosurgical patients were included in this prospective study. 95 completed questionnaires were included. RESULTS: 75% patients achieved the best possible treatment score (S3T3M4). Of the 25% of patients who did not achieve this ideal outcome, the most common cause was either medical deterioration 18%, or technical complications of surgery discussed during the consent process 17%, or both. Surgeons rated their outcomes as expectations exceeded in 2% of cases, met in 92%, partially met in 5% and failed in 1%. Patients rated their outcomes as expectations exceeded in 37%, met in 37%, partially met in 18%, and 5% reported that their expectations were not met or they were worse than before the operation. Bivariate correlation analysis (Pearson's r coefficient) between overall 'expectation score' of patients and surgeons showed moderate correlation with r = .25 (p = .014). CONCLUSION: NECS score can be used as an indicator to assess technical performance and patient satisfaction. It provides a more balanced quality indicator of the surgical service delivery than COP. It also offers additional advantages for auditing/planning improving care and may serve as an appraisal/revalidation tool.

Spinal cord stimulation during the antepartum and intrapartum periods: a case report showing no deleterious effect of conventional paraesthesia producing stimulation.

We report on a 25-year-old woman who used her spinal cord stimulator (SCS), previously inserted for chronic regional pain syndrome (CPRS), to assist with both chronic and pregnancy-related pain management. We describe the therapeutic effect of the stimulator and briefly highlight the issues surrounding the use of SCS during pregnancy.

'Pseudofailure' of spinal cord stimulation for neuropathic pain following a new severe noxious stimulus: learning points from a case series of failed spinal cord stimulation for complex regional pain syndrome and failed back surgery syndrome.

Failure of spinal cord stimulation (SCS) may be due to hardware problems, migration of electrodes and, in the long-term, plasticity in the spinal cord with habituation to the stimulation current. We describe a series of seven patients who experienced acute therapeutic loss of SCS effects following an acute nociceptive event unrelated to primary pathology. There were no hardware problems. We called this 'Pseudofailure', as the effective stimulation returned in all patients following a period off stimulation or reprogramming. This phenomenon has not been reported previously in the literature. Over a 4-year period, we managed seven patients with this feature: four had received SCS for complex regional pain syndrome and three for failed back surgery syndrome. In all seven cases, there was cessation of the pain relief afforded by SCS following an acute painful event: four patients had trauma, two patients had domestic electric shock and one patient suffered shingles (varicella zoster infection). We excluded hardware-related problems in all cases. In two patients, SCS effects could be regained by an initial attempt at reprogramming. In the remaining five cases reprogramming was unsuccessful, and stimulation was switched off for several months before recommencing, when we discovered a return of good therapeutic effect. We conclude that SCS may seem to fail following a separate strong nociceptive stimulus. Stimulation may be regained with reprogramming or following a period with stimulation switched off. We would, therefore, advise against removal of SCS hardware in the first instance.

Corneal hypoesthesia with normal sub-basal nerve density following surgery for trigeminal neuralgia.

PURPOSE: To evaluate the corneal sub-basal nerve plexus in patients presenting with hypoesthesia following surgery for trigeminal neuralgia. METHODS: Twenty-one patients who had unilateral medically uncontrolled trigeminal neuralgia and underwent ipsilateral surgery from 2006 to 2012 were included. Of these, 10 had microvascular decompression (MVD group) and 11 had balloon compression of the trigeminal ganglion (BC group). Slit lamp examination, Cochet-Bonnet aesthesiometery and in vivo confocal microscopy were carried out on both eyes of each patient. Nerve density data were statistically analysed. RESULTS: Corneal sensations and sub-basal nerve densities in MVD group were normal and equal in both the operated and unoperated sides, indicating that there was no intra-operative damage of the ophthalmic division of the trigeminal nerve (V1). However, those in BC group, despite having significantly reduced corneal sensations on the operated side (p = 0.007), did not demonstrate any significant difference in their sub-basal nerve densities (p = 0.477). No patient had any ocular symptoms. CONCLUSIONS: This study supports the hypothesis that complete ganglionic damage and/or postganglionic damage of V1 results in corneal hypoesthesia and neurotrophic keratitis, but partial ganglionic or preganglionic damage would preserve trophic function despite hypoesthesia and not result in clinically significant symptoms or signs of neurotrophic keratitis. The trophic and sensory functions of V1 are therefore independent and can be dissociated by disease or injury.

Socio-economic characteristics of patients with glioblastoma multiforme.

The incidence of glioblastoma multiforme (GBM) varies across the world and also within subpopulations within each nation. Many cancers show correlation with socioeconomic status and we hypothesised that incidence of GBM also does the same. We performed a retrospective analysis of all patients treated with brain tumours at a single hospital over a 6-year period. For these patients we examined markers of socioeconomic status and reviewed their histopathological diagnosis. A total of 2859 patients had surgery between April 2006 and April 2012. Of these 880 had histological diagnosis of GBM. Records for all patients were reviewed. Based on postcodes, socioeconomic data was obtained at ward level from government sources. Markers were: average weekly household income, percentage unemployed, population density, indices of deprivation and percentage of households with no car. Data was analysed for trends between incidence per ward and socio-economic markers. Increasing incidence of GBM was associated with increasing wage (p = 0.044), less unemployment (p = 0.0002), Indices of Multiple Deprivation (p = 0.05), lower population density (p = 0.0015) and greater ownership of cars (p = 0.0005). There are unique socioeconomic characteristics for patients with GBM. Although a link to aetiology cannot be established from this limited epidemiological study, these results identify issues that these patients are more likely to face. These should be taken into account when planning support services and patient care following surgery.

An interpretative phenomenological analysis of the patient experience of awake craniotomy: brain tumour diagnosis to discharge.

OBJECTIVES: Previous research exploring the patient experience of awake craniotomy (AC) has yielded contrasting accounts. The current study aimed to explore the lived experience of having undergone an AC in the United Kingdom. DESIGN: This was a qualitative, semi-structured interview study. Interviews were audio-recorded and transcribed verbatim. Data were analysed using interpretative phenomenological analysis (IPA). METHODS: Seven participants (three males, four females) who had undergone an AC in the United Kingdom took part in the study. Ages ranged between 26 and 41 years old at the time of interview. Time since AC ranged from 5 months to 4 years. RESULTS: Participants appeared to be satisfied with, and tolerant of, the AC experience. Three superordinate themes: use of self-preservation strategies prior to and during AC, a bizarre yet pleasant operation experience, and the need for more concrete information prior to surgery were identified. These themes appeared to be embedded in a core theme: relationship with the neurosurgeon. CONCLUSIONS: The relationship with the neurosurgeon appears crucial to the patient experience of AC. This knowledge underscores the need for effective doctor-patient communication skills which could lead to improved delivery of care and more positive outcomes.