Locating the ventral intermediate thalamic nucleus for deep brain stimulation surgery: analysis of a case series comparing CT and MR targeting.

BACKGROUND: Deep brain stimulation (DBS) surgery targeting the ventral intermediate thalamic nucleus (Vim) has proven efficacy in the treatment of tremor. AIMS: The primary aim is to investigate whether there is a statistically significant difference in patient outcomes when CT-guided targeting of the Vim is compared with MRI-guided targeting. METHODS: This is a retrospective study concerning patients undergoing Vim-targeted DBS at the Department of Neurosurgery, Royal Victoria Infirmary in Newcastle (9th August 2012 to 4th January 2019). Fahn-Tolosa-Marin Tremor Scale (FTM TS) and EQ-5D scores were collected from patient notes. Statistical analysis was performed using IBM® SPSS® Statistics Version 24. Independent samples t-tests were used to compare means. RESULTS: Independent samples t-test did not reveal a statistically significant difference between CT (n = 10; FTM TS mean = 65.40, SD = 11.40; EQ-5D mean = 39.50, SD = 17.87) and MR (n = 7; FTM TS mean = 60.57, SD = 7.50; EQ-5D mean = 32.14, SD = 9.94) groups in pre-surgery FTM TS (t(15) = 0.977, p = 0.344) and EQ-5D (t(15) = 0.982, p = 0.342) scores. No statistically significant difference between the CT (FTM TS mean = 24.12, SD = 20.47; EQ-5D mean = 75.56, SD = 15.63) and MR (FTM TS mean = 22.86, SD = 6.72; EQ-5D mean = 70.43, SD = 15.48) groups was revealed at 1 year assessment of FTM TS (t(14) = 0.155, p = 0.879) and EQ-5D (t(14) = 0.654, p = 0.524). The median difference between pre- and post-surgery FTM TS and EQ-5D scores in the CT group at 1 year was 43.00 and 35.00, respectively. The MR patient group median difference in pre- and post-surgery at 1 year was 35.00 and 35.00 respectively. CONCLUSION: No statistically significant difference between CT and MR image-guided targeting patient groups was detected.

Patient selection and outcome of deep brain stimulation for multiple sclerosis-associated tremor.

INTRODUCTION: Tremor is a disabling symptom of multiple sclerosis (MS), with limited treatment modalities. Thalamic ventral-intermediate-nucleus (VIM) deep brain stimulation (DBS) is a method of neuromodulation. We describe the long-term outcomes of our carefully selected patients who underwent VIM DBS for their MS-associated tremor. METHODS: Patients were referred from the regional neurology units. Pre-operative assessments included suitability for anesthesia, tremor quantification by the Fahn-Tolosa-Marin scores, and quality-of-life (EQ5D) measures. Exclusion criteria included prominent cerebellar symptoms such as ataxia and dysmetria, intracranial pathology such as ventriculomegaly, cerebellar plaques and thalamic abnormality, and comorbid psychiatric symptoms. Seven patients (3M:4F) underwent DBS for MS-associated tremor between September 2013 and February 2019. Mean age was 42 years (±SD 8 years). DBS was performed at a mean of 13 years (±SD 9 years) after diagnosis of MS. RESULTS: There were no postoperative surgical complications. All patients showed improvement in FTM tremor scores, by up to 61% at 6 months postoperatively. There was an improvement of 30-175% in quality-of-life scores at 6 months. Improvement of tremor and quality of life, over baseline, was sustained over a long period of follow-up (mean 26.6 months ± SD 20.7 months), including our longest duration at 72 months. CONCLUSION: With careful selection, DBS is a safe, efficacious intervention for MS-tremor and can positively impact on tremor and quality of life, with effects over a long period. As patients live longer with MS and the advent of new therapies, DBS should be considered for selected patients.

Late Frontal Bone Reconstruction Using Three-Dimensional Printed Models for Titanium Mesh Customization: A Case Series.

BACKGROUND: The convex frontal bone is covered by thin skin, rendering its reconstruction cosmetically challenging. Customized alloplastic implants provide better contouring than autologous bone, yet their high cost and availability limit their application. We assess customized titanium mesh implants precontoured using patient-specific three-dimensional (3D) printed models for late frontal cranioplasty. METHODS: We retrospectively analyzed the prospectively collected cases of unilateral frontal titanium mesh cranioplasty with 3D printing-assisted preplanning from 2017 to 2019. We used two 3D-printed patient-specific skull models for preoperative planning: a mirrored normal model for implant contouring and a defect model for edge trimming and fixation planning. The endoscope was used in 4 cases for percutaneous mesh fixation. We documented postoperative complications. We assessed the reconstruction symmetry clinically, and radiologically on postoperative computed tomography. RESULTS: Fifteen patients were included. The duration after previous surgery ranged from 8 to 24 months. Four patients developed complications, which were managed conservatively. Favorable cosmetic outcomes were achieved in all patients. CONCLUSIONS: Precontouring of titanium mesh implants using in-house 3D-printed models could optimize cosmetic and surgical outcomes in late frontal cranioplasty. Preoperative planning could permit minimal access surgery, which could be aided by the endoscope in select cases.

Traumatic arteriovenous fistula from internal maxillary artery following trigeminal balloon compression.

We describe the development of a direct traumatic arteriovenous fistula arising from the internal maxillary artery after an uneventful percutaneous trigeminal balloon compression for trigeminal neuralgia, and its management through embolization and radiosurgery.

Surgical management of anterior sacral meningoceles: an illustrated case series and review of the literature.

BACKGROUND: Anterior sacral meningocele (ASM) is an uncommon variant of spinal dysraphism. Surgical correction for this condition is challenging and optimal corrective approaches are uncertain. OBJECTIVE: To share our experience of managing this rare condition using the posterior trans-sacral approach and provide a contemporary review of the literature. METHODS: Retrospective review of case notes, operative records, and imaging of eligible patients treated via the posterior trans-sacral approach between 2006 and 2020 at our regional neurosciences centre. RESULTS: Three patients, two females and one male with a mean age of 30 years (range 16-38), were treated. Presenting symptoms included lower abdominal pain and recurrent miscarriages. Patients underwent corrective surgery using the posterior approach involving a sacral laminectomy, durotomy and closure of the communicating fistula. A single patient required reoperation due to early recurrence. Another patient proved challenging because of a very large sacral fistula and required two procedures due to the development of high-pressure headaches secondary to a recurrence. All patients improved symptomatically postoperatively and remained symptom free at the last clinic follow-up and have been discharged. Following review of the literature, only two other non-syndromic cases have been described. CONCLUSIONS: ASM is an uncommon congenital abnormality, typically presenting with mass effect symptoms secondary to a presacral cystic mass. Surgical management using a posterior approach to close the meningeal sac is feasible and less invasive than an anterior approach. Long term clinical outcomes in our series were satisfactory.

Vagus nerve stimulation paired with rehabilitation for stroke: Implantation experience from the VNS-REHAB trial.

OBJECTIVE: Vagus Nerve Stimulation (VNS) paired with rehabilitation delivered by the Vivistim® Paired VNS™ System was approved by the FDA in 2021 to improve motor deficits in chronic ischemic stroke survivors with moderate to severe arm and hand impairment. Vagus nerve stimulators have previously been implanted in over 125,000 patients for treatment-resistant epilepsy and the surgical procedure is generally well-tolerated and safe. In this report, we describe the Vivistim implantation procedure, perioperative management, and complications for chronic stroke survivors enrolled in the pivotal trial. METHODS: The pivotal, multisite, randomized, triple-blind, sham-controlled trial (VNS-REHAB) enrolled 108 participants. All participants were implanted with the VNS device in an outpatient procedure. Thrombolytic agents were temporarily discontinued during the perioperative period. Participants were discharged within 48 hrs and started rehabilitation therapy approximately 10 days after the Procedure. RESULTS: The rate of surgery-related adverse events was lower than previously reported for VNS implantation for epilepsy and depression. One participant had vocal cord paresis that eventually resolved. There were no serious adverse events related to device stimulation. Over 90% of participants were taking antiplatelet drugs (APD) or anticoagulants and no adverse events or serious adverse events were reported as a result of withholding these medications during the perioperative period. CONCLUSIONS: This study is the largest, randomized, controlled trial in which a VNS device was implanted in chronic stroke survivors. Results support the use of the Vivistim System in chronic stroke survivors, with a safety profile similar to VNS implantations for epilepsy and depression.

An eye on the future for defeating hydrocephalus, ciliary dyskinesia-related hydrocephalus: review article.

Congenital hydrocephalus affects approximately one in 1000 newborn children and is fatal in approximately 50% of untreated cases. The currently known management protocols usually necessitate multiple interventions and long-term use of healthcare resources due to a relatively high incidence of complications, and many of them mostly provide a treatment of the effect rather than the cause of cerebrospinal fluid flow reduction or outflow obstruction. Future studies discussing etiology specific hydrocephalus alternative treatments are needed. We systematically reviewed the available literature on the effect of ciliary abnormality on congenital hydrocephalus pathogenesis, to open a discussion on the feasibility of factoring ciliary abnormality in future research on hydrocephalus treatment modalities. Although there are different forms of ciliopathies, we focused in this review on primary ciliary dyskinesia. There is growing evidence of association of other ciliary syndromes and hydrocephalus, such as the reduced generation of multiple motile cilia, which is distinct from primary ciliary dyskinesia. Data for this review were identified by searching PubMed using the search terms 'hydrocephalus,' 'Kartagener syndrome,' 'primary ciliary dyskinesia,' and 'immotile cilia syndrome.' Only articles published in English and reporting human patients were included. Seven studies met our inclusion criteria, reporting 12 cases of hydrocephalus associated with primary ciliary dyskinesia. The patients had variable clinical presentations, genetic backgrounds, and ciliary defects. The ependymal water propelling cilia differ in structure and function from the mucus propelling cilia, and there is a possibility of isolated non-syndromic ependymal ciliopathy causing only hydrocephalus with growing evidence in the literature for the association ependymal ciliary abnormality and hydrocephalus. Abdominal and thoracic situs in children with hydrocephalus can be evaluated, and secondary damage of ependymal cilia causing hydrocephalus in cases with generalized ciliary abnormality can be considered.

A career in neurosurgery: perceptions and the impact of a national SBNS/NANSIG neurosurgery careers day.

OBJECTIVE: Entrance to neurosurgical training is highly competitive. Without proper advice, information and opportunities, talented individuals may be dissuaded from applying. The Neurology and Neurosurgery Interest Group (NANSIG) organises a Careers Day in Neurosurgery every year. Our objective was to assess the overall utility of a neurosurgery careers day and the perceived factors that attract and detract from the specialty, from attendees of the ninth annual neurosurgery careers day. METHODS: Eighteen-item pre-conference and 19-item post-conference questionnaires were disseminated electronically to conference attendees. Questions aimed to capture: (i) baseline demographics; (ii) previous experience and exposure in neurosurgery; (iii) interest in neurosurgery; (iv) understanding training and a career in neurosurgery; (v) perceived factors of attraction and dissuasion of neurosurgery; and (vi) perceived value, quality and educational purpose of the conference. RESULTS: In total, 77 delegates attended the careers day. Most did not have a formal neurosurgical rotation during medical school (24.7%, n = 19), but almost half had gained neurosurgical experience and presented research work. The careers day increased knowledge of the neurosurgical application process (median Likert score 3/5 to 4/5, p < 0.01), duration of training (72.7-88.3%), and desire to pursue a career in neurosurgery (75.3-81.8%). The most commonly reported factors attracting delegates to neurosurgery were interest in neuroanatomy (80.5%, n = 62), practical skills (64.9%, n = 50), and impact on patients (62.3%, n = 48). The most common dissuasive factors were competition to entry (64.9%, n = 50), long working hours (40.3%, n = 31), and other career interests (35.1%, n = 27). Almost all would recommend the event to a colleague (94.9%, n = 73). CONCLUSIONS: Formal undergraduate exposure to neurosurgery is limited. Neurosurgery careers days increase awareness and understanding of the application process and improve interest in a selected cohort. The factors attracting applicants to neurosurgery remain practical links to neuroanatomy, opportunities in neurosurgery for innovation and research, and direct impact on patients.

Hosting an Educational Careers Day Within the Virtual Paradigm: The Neurology and Neurosurgery Interest Group Experience.

INTRODUCTION:  To explore our experience of hosting the 10th Annual Neurology and Neurosurgery Interest Group-Society of British Neurological Surgeons (NANSIG-SBNS) Neurosurgery Careers Day, held virtually for the first time. METHODS:  Reflective feedback and review of an international, virtual neurosurgery careers day. The authors reflect on the logistics of organizing the event, and the pre- and post-event feedback provided by delegates. Recommendations have been made on how to successfully host a virtual event. The key themes that permeated the event have been outlined and discussed in the context of the feedback received. RESULTS:  The event was attended by 231 delegates from 20 countries worldwide. Knowledge of neurosurgery as a career and the application process increased after attending the careers day (4.27/5 to 4.51/5, p=0.003 and 3.12/5 to 4.31/5, p<0.001 respectively). The key themes identified from the event include attendance, networking, and education. Qualitative feedback was positive and indicated a positive perception of the careers day. CONCLUSIONS:  The future of educational events is unclear, and a hybrid approach is recommended to retain the benefits of the online space when in-person events eventually return.

The Neurology and Neurosurgery Interest Group (NANSIG)-ten years of cultivating interest in clinical neurosciences.

Collaboration and successful teamworking are important components of clinical practise, and these skills should be cultivated early in medical school. The breadth of current medical school curricula means that students often have limited exposure to clinical neurosciences. Since its inception in 2009, the Neurology and Neurosurgery Interest Group (NANSIG) has become a national (UK and Republic of Ireland) example of student and junior doctor synergistic collaboration to deliver educational materials, research, conferences, seminars and workshops, as well as advocating for diversity in this field. Recently, it has expanded to incorporate an international audience and cater for a larger group of young medical professionals. The organisation has overcome numerous challenges and is constantly innovating new approaches to harness the necessary knowledge, skills and network to succeed in a career in neurosciences, neurology and neurosurgery. This article summarises the initiatives undertaken by the group over its first 10 years of existence and its organisational structure, as well as its future plans.

Delayed presentation of bamboo foreign body in brainstem, with novel skull base foramen.

We describe the extremely unusual case of a childhood injury to the skull base presenting after many years, as a foreign body with chronic granulomatous infection of the brainstem, mimicking neoplasm. TB had an inconsequential penetrating injury to the left cheek, from a bamboo spike aged 15. After 4 years, he developed worsening left sided weakness, imaging at this time was normal. After a car accident aged 40, the weakness worsened further and imaging demonstrated a foreign body entering the skull base. At its tip, it had caused a chronic granulomatous reaction within the brainstem. Surgical removal of this bamboo splinter was via an infratemporal, transzygomatic craniotomy and TB made a good recovery postoperatively. This unusual case demonstrates the important of close inspection of imaging, and thorough history taking. It also questions the chronology of the ossification of the skull base.

CSF rhinorrhoea after endonasal intervention to the anterior skull base (CRANIAL): proposal for a prospective multicentre observational cohort study.

BACKGROUND: The endonasal transsphenoidal approach (TSA) has emerged as the preferred approach in order to treat pituitary adenoma and related sellar pathologies. The recently adopted expanded endonasal approach (EEA) has improved access to the ventral skull base whilst retaining the principles of minimally invasive surgery. Despite the advantages these approaches offer, cerebrospinal fluid (CSF) rhinorrhoea remains a common complication. There is currently a lack of comparative evidence to guide the best choice of skull base reconstruction, resulting in considerable heterogeneity of current practice. This study aims to determine: (1) the scope of the methods of skull base repair; and (2) the corresponding rates of postoperative CSF rhinorrhoea in contemporary neurosurgical practice in the UK and Ireland. METHODS: We will adopt a multicentre, prospective, observational cohort design. All neurosurgical units in the UK and Ireland performing the relevant surgeries (TSA and EEA) will be eligible to participate. Eligible cases will be prospectively recruited over 6 months with 6 months of postoperative follow-up. Data points collected will include: demographics, tumour characteristics, operative data), and postoperative outcomes. Primary outcomes include skull base repair technique and CSF rhinorrhoea (biochemically confirmed and/or requiring intervention) rates. Pooled data will be analysed using descriptive statistics. All skull base repair methods used and CSF leak rates for TSA and EEA will be compared against rates listed in the literature. ETHICS AND DISSEMINATION: Formal institutional ethical board review was not required owing to the nature of the study - this was confirmed with the Health Research Authority, UK. CONCLUSIONS: The need for this multicentre, prospective, observational study is highlighted by the relative paucity of literature and the resultant lack of consensus on the topic. It is hoped that the results will give insight into contemporary practice in the UK and Ireland and will inform future studies.

CT scan exposure in children with ventriculo-peritoneal shunts: single centre experience and review of the literature.

PURPOSE: A computed tomography (CT) scan in childhood is associated with a greater incidence of brain cancer. CT scans are used in patients with ventriculo-peritoneal (VP) shunts in whom shunt dysfunction is suspected. We wanted to assess the CT scan exposure in a cohort of children with VP shunts and attempt to quantify their radiation exposure. METHODS: A single-centre retrospective analysis was performed recording CT head scans in children younger than 18 years with VP shunts. Hospital coding data was cross-referenced with electronic records and radiology databases both in our neurosurgery unit and in hospitals referring to it. RESULTS: One hundred and fifty-two children with VP shunts were identified. The mean time with shunt in situ was 5.4 years (± 4.61). A mean of 3.33 CT scans (range 0-20) were performed on each child, amounting to 0.65 (± 0.87) CTs per shunt year. Based on 2 msv of radiation per scan, this equates to an average exposure of 1.31 msv per child per shunt year. CONCLUSION: Children who have multiple CT head scans for investigation of possible shunt dysfunction are at a greater risk of developing cancer. We discuss the implications of this increased risk and discuss strategies to limit radiation exposure in children with VP shunts.

The role of astrocytes in seizure generation: insights from a novel in vitro seizure model based on mitochondrial dysfunction.

Approximately one-quarter of patients with mitochondrial disease experience epilepsy. Their epilepsy is often severe and resistant towards conventional antiepileptic drugs. Despite the severity of this epilepsy, there are currently no animal models available to provide a mechanistic understanding of mitochondrial epilepsy. We conducted neuropathological studies on patients with mitochondrial epilepsy and found the involvement of the astrocytic compartment. As a proof of concept, we developed a novel brain slice model of mitochondrial epilepsy by the application of an astrocytic-specific aconitase inhibitor, fluorocitrate, concomitant with mitochondrial respiratory inhibitors, rotenone and potassium cyanide. The model was robust and exhibited both face and predictive validity. We then used the model to assess the role that astrocytes play in seizure generation and demonstrated the involvement of the GABA-glutamate-glutamine cycle. Notably, glutamine appears to be an important intermediary molecule between the neuronal and astrocytic compartment in the regulation of GABAergic inhibitory tone. Finally, we found that a deficiency in glutamine synthetase is an important pathogenic process for seizure generation in both the brain slice model and the human neuropathological study. Our study describes the first model for mitochondrial epilepsy and provides a mechanistic insight into how astrocytes drive seizure generation in mitochondrial epilepsy.

Human and rodent temporal lobe epilepsy is characterized by changes in O-GlcNAc homeostasis that can be reversed to dampen epileptiform activity.

Temporal Lobe Epilepsy (TLE) is frequently associated with changes in protein composition and post-translational modifications (PTM) that exacerbate the disorder. O-linked-ß-N-acetyl glucosamine (O-GlcNAc) is a PTM occurring at serine/threonine residues that is derived from and closely associated with metabolic substrates. The enzymes O-GlcNActransferase (OGT) and O-GlcNAcase (OGA) mediate the addition and removal, respectively, of the O-GlcNAc modification. The goal of this study was to characterize OGT/OGA and protein O-GlcNAcylation in the epileptic hippocampus and to determine and whether direct manipulation of these proteins and PTM's alter epileptiform activity. We observed reduced global and protein specific O-GlcNAcylation and OGT expression in the kainate rat model of TLE and in human TLE hippocampal tissue. Inhibiting OGA with Thiamet-G elevated protein O-GlcNAcylation, and decreased both seizure duration and epileptic spike events, suggesting that OGA may be a therapeutic target for seizure control. These findings suggest that loss of O-GlcNAc homeostasis in the kainate model and in human TLE can be reversed via targeting of O-GlcNAc related pathways.

Perampanel and decanoic acid show synergistic action against AMPA receptors and seizures.

Perampanel is an adjunctive treatment for epilepsy that works through the direct inhibition of AMPA receptors. The same molecular mechanism has recently been shown for a fatty acid, decanoic acid, prescribed in the medium chain triglyceride ketogenic diet for the treatment of patients with drug-resistant epilepsy. Because each compound has been proposed to act through a distinct AMPA receptor binding site, we predicted that perampanel and decanoic acid would act synergistically against AMPA receptors and, consequently, seizures. Here, we show a synergistic interaction between perampanel and decanoic acid in direct AMPA receptor inhibition, in an ex vivo model of seizure activity, and against seizure-induced activity in human brain slices. These data support a potential role for combination treatment using perampanel and dietary decanoic acid to provide enhanced seizure control.

Enhanced interlaminar excitation or reduced superficial layer inhibition in neocortex generates different spike-and-wave-like electrographic events in vitro.

Acute in vitro models have revealed a great deal of information about mechanisms underlying many types of epileptiform activity. However, few examples exist that shed light on spike-and-wave (SpW) patterns of pathological activity. SpW are seen in many epilepsy syndromes, both generalized and focal, and manifest across the entire age spectrum. They are heterogeneous in terms of their severity, symptom burden, and apparent anatomical origin (thalamic, neocortical, or both), but any relationship between this heterogeneity and underlying pathology remains elusive. In this study we demonstrate that physiological delta-frequency rhythms act as an effective substrate to permit modeling of SpW of cortical origin and may help to address this issue. For a starting point of delta activity, multiple subtypes of SpW could be modeled computationally and experimentally by either enhancing the magnitude of excitatory synaptic events ascending from neocortical layer 5 to layers 2/3 or selectively modifying superficial layer GABAergic inhibition. The former generated SpW containing multiple field spikes with long interspike intervals, whereas the latter generated SpW with short-interval multiple field spikes. Both types had different laminar origins and each disrupted interlaminar cortical dynamics in a different manner. A small number of examples of human recordings from patients with different diagnoses revealed SpW subtypes with the same temporal signatures, suggesting that detailed quantification of the pattern of spikes in SpW discharges may be a useful indicator of disparate underlying epileptogenic pathologies. NEW & NOTEWORTHY Spike-and-wave-type discharges (SpW) are a common feature in many epilepsies. Their electrographic manifestation is highly varied, as are available genetic clues to associated underlying pathology. Using computational and in vitro models, we demonstrate that distinct subtypes of SpW are generated by lamina-selective disinhibition or enhanced interlaminar excitation. These subtypes could be detected in at least some noninvasive patient recordings, suggesting more detailed analysis of SpW may be useful in determining clinical pathology.