ObjectivesThis study aims to refine computer-assisted planning (CAP) of SEEG implantations by adding spatial constraints from prior SEEG trajectories (“Priors”) to improve safety and reduce manual adjustments, without increasing planning time.MethodsRetrospective validation based on 159 previously implanted trajectories (11 cases) planned by the clinical standard CAP and CAP constrained with spatial priors (“CAP + Priors”). Constraints included 31 target and 51 entry zones, created from 98 consecutive patients (763 implanted SEEG trajectories). Each of the 159 previously implanted trajectories was planned by two fellows, once with CAP and once with CAP + Priors, in a randomized order. The time taken to generate the initial computer-generated plan (T1) and the user-edited final plan (T2) were recorded together with the proportions of electrodes that required subsequent adjustments. Clinical implantability was assessed via a blinded review of each trajectory by five independent epilepsy neurosurgeons with expertise in SEEG implantation.ResultsExpert raters considered 88.5% of trajectories implantable, with no difference in acceptability between CAP alone and CAP + Priors (p = 0.79). Median (IQR) T1 for CAP to produce complete automated implantation was 4.6 (0.85) min vs. CAP + Priors was 6.3 (2.6) min (p = 0.03). There was no significant difference in T2 (time to complete surgeon-edited plan): CAP median (IQR) 105 (22) min, and CAP + Priors median (IQR) 96 (68) min (p = 0.92). The CAP + Priors risk score was significantly lower than that for the previously actually implanted trajectories for the 11 plans analyzed (p = 0.004), and no different from CAP alone planning. A significant reduction was observed in manual adjustments required with CAP + Priors in the cingulate gyrus.ConclusionUsing spatial priors from previous implantations enhances SEEG CAP and increases the granularity of trajectory planning. This approach facilitates more standardized planning and allows for the incorporation of experience from multiple expert centers, decreasing the risk of the resultant trajectories and reducing the proportion of trajectories that require manual planning without significantly increasing planning time.

Anteromesial temporal lobe resection (ATLR) is a useful treatment option for drug-resistant mesial temporal lobe epilepsy (DRmTLE). Growing evidence suggests the piriform cortex plays a crucial role in the generation and propagation of seizures in DRmTLE - and that the resection of the temporal portion of the piriform cortex is associated with significantly improved rates of seizure freedom. Here, we present the resection of the temporal portion of the piriform cortex in ATLR, using high-resolution preoperative probabilistic tractography algorithms and fused anatomical masks of the structures of interest into the intraoperative neuronavigation and microscope head-up display (HUD). All patients undergoing comprehensive preoperative assessment and investigations for DRmTLE provided informed, written consent to record an intraoperative video of the procedure. Patients were identified by an expert multidisciplinary team of epileptologists, epilepsy neurosurgeons, neuropsychologists, neuropsychiatrists, and electrophysiologists at a large epilepsy surgery center. The preoperative imaging pipeline included the delineation of critical structures. This included the temporal piriform cortex, and high-resolution probabilistic tractography for essential tracts at risk (e.g., optic radiation and inferior fronto-occipital fasciculus). These were co-registered to the preoperative volumetric neuronavigation scan and uploaded to the intra-operative neuronavigation system. Presented here is a step-by-step procedure of ATLR, including the resection of the temporal portion of the piriform cortex. The protocol combines Advanced structural and diffusion MR imaging and intraoperative visual aids to integrate anatomical masks of critical grey matter structures and white matter tracts into the surgical workflow in the operating room.

Objectives Computer-assisted planning (CAP) allows faster SEEG planning and improves grey matter sampling, orthogonal drilling angles to the skull, reduces risk scores and minimises intracerebral electrode length. Incorporating prior SEEG trajectories enhances CAP planning, refining output with centre-specific practices. This study significantly expands on the previous work, compares priors libraries between two centres, and describes differences between SEEG in adults and children in these centres. Methods 98 adults and 61 children who underwent SEEG implantation as part of epilepsy surgery investigations were included. Priors libraries were created for each population, clustered by target regions and subdivided by cortical approaches. The libraries were coregistered and quantitatively and qualitatively compared. Results The average number of implanted electrodes per patient was higher in paediatric patients than adults (13.6 vs 8.0). Paediatric implantations focused more on the insula than adult implantations (38.0 % vs 13.5 %), with similar proportions of electrodes implanted in the temporal and parietal lobes, and a higher proportion of adult electrodes in the frontal and orbitofrontal regions (40.6 % vs 24.0 %). Correspondence between the priors libraries was high. We present an example of a complex insular implantation planned with paediatric spatial priors and illustrate resultant SEEG recordings. Discussion The use of centre-specific spatial priors allows the incorporation of surgeon-specific and unit-specific preferences into automated planning. We compare implantation styles between a paediatric and an adult centre, discussing similarities and differences. This tool allows centres to compare practice and represents an effective way to analyse implantation strategies that is agnostic to method of implantation.

Introduction Temporal encephalocoeles are a recognised cause of drug-resistant temporal lobe epilepsy (TLE), with uncertain associations to epileptogenesis and an unclear optimal management approach. Operative management, particularly resective temporal lobe surgery, has been proposed, but outcomes and decision-making criteria remain debated. This study aims to evaluate the outcomes of surgically and non-surgically managed patients with temporal encephalocoeles in the context of drug-resistant TLE, focusing on seizure freedom rates, postoperative complications and factors influencing management decisions. Methods A retrospective, single-centre study was conducted based on all adult TLE patients with temporal encephalocoeles encountered between March 2017 and August 2023. Patients were classified into three groups: those discussed at an epilepsy surgery multidisciplinary team (MDT) meeting and managed surgically (surgical group), those discussed at an MDT and managed non-surgically (non-surgical group) and those radiologically identified by reporting neuroradiologists but not discussed at MDT (radiologically diagnosed group). Clinical, electrophysiological, radiological and surgical data were compared across the groups, including radiological features of raised intracranial pressure (ICP) that have been postulated as a cause for temporal encephaloceles. Results We included 24 adult patients with temporal encephalocoeles: eight in the surgical group, eight in the non-surgical group and eight in the radiologically diagnosed group. The mean age at diagnosis was 39.3 ± 13.6 years and clinical features were comparable across groups. Operative management was decided by an experienced epilepsy surgery MDT, involving resection of the anterior temporal pole with (4/8, 50 %) or without (50 %) mesial temporal structures, resulted in a seizure freedom rate of 87.5 %. In contrast, no patient in the non-surgical or radiologically diagnosed groups achieved seizure freedom (0 %). Postoperative complications included one patient who developed hydrocephalus and required a ventriculoperitoneal shunt, and another who developed a pseudomeningocoele. Radiological markers of raised ICP were broadly similar across the groups, with the exception of increased optic nerve sheath diameter in the non-surgical group (p = 0.032). Conclusion Our study demonstrates that excellent post-operative outcomes are achievable with temporal lobe resections. A standardised presurgical evaluation pathway and management protocol are essential to ensure timely identification of temporal encephalocoeles on imaging, facilitating preoperative planning and optimising surgical outcomes. CSF hydrodynamic disturbances may occur after surgery for encephaloceles and individualised evaluation is therefore crucial to select the most appropriate management approach.

A greater extent of resection of the temporal portion of the piriform cortex (PC) has been shown to be associated with higher likelihood of seizure freedom in adults undergoing anterior temporal lobe resection (ATLR) for drug‐resistant temporal lobe epilepsy (TLE). There have been no such studies in children, therefore this study aimed to investigate this association in a pediatric cohort.

INTRODUCTION:Anteromesial temporal lobe resection is the most common surgical technique used to treat drug-resistant mesial temporal lobe epilepsy, particularly when secondary to hippocampal sclerosis. Structural and functional imaging data suggest the importance of sparing the posterior hippocampus for minimising language and memory deficits. Recent work has challenged the view that maximal posterior hippocampal resection improves seizure outcome. This study was designed to assess whether resection of posterior hippocampal atrophy was associated with improved seizure outcome. METHODS:Retrospective analysis of a prospective database of all anteromesial temporal lobe resections performed in individuals with hippocampal sclerosis at our epilepsy surgery centre, 2013-2021. Pre- and post-operative MRI were reviewed by 2 neurosurgical fellows to assess whether the atrophic segment, displayed by automated hippocampal morphometry, was resected, and ILAE seizure outcomes were collected at 1 year and last clinical follow-up. Data analysis used univariate and binary logistic regression. RESULTS:Sixty consecutive eligible patients were identified of whom 70% were seizure free (ILAE Class 1 & 2) at one year. There was no statistically significant difference in seizure freedom outcomes in patients who had complete resection of atrophic posterior hippocampus or not (Fisher's Exact test statistic 0.69, not significant at p < .05) both at one year, and at last clinical follow-up. In the multivariate analysis only a history of status epilepticus (OR=0.2, 95%CI:0.042-0.955, p = .04) at one year, and pre-operative psychiatric disorder (OR=0.145, 95%CI:0.036-0.588, p = .007) at last clinical follow-up, were associated with a reduced chance of seizure freedom. SIGNIFICANCE:Our data suggest that seizure freedom is not associated with whether or not posterior hippocampal atrophy is resected. This challenges the traditional surgical dogma of maximal posterior hippocampal resection in anteromesial temporal lobe resections and is a step further optimising this surgical procedure to maximise seizure freedom and minimise associated language and memory deficits.

BACKGROUND AND OBJECTIVES:In medically refractory temporal lobe epilepsy (TLE), 30%-50% of patients experience substantial language decline after resection in the language-dominant hemisphere. In this study, we investigated the contribution of white matter fiber bundle damage to language change at 3 and 12 months after surgery. METHODS:We studied 127 patients who underwent TLE surgery from 2010 to 2019. Neuropsychological testing included picture naming, semantic fluency, and phonemic verbal fluency, performed preoperatively and 3 and 12 months postoperatively. Outcome was assessed using reliable change index (RCI; clinically significant decline) and change across timepoints (postoperative scores minus preoperative scores). Functional MRI was used to determine language lateralization. The arcuate fasciculus (AF), inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus, middle longitudinal fasciculus (MLF), and uncinate fasciculus were mapped using diffusion MRI probabilistic tractography. Resection masks, drawn comparing coregistered preoperative and postoperative T1 MRI scans, were used as exclusion regions on preoperative tractography to estimate the percentage of preoperative tracts transected in surgery. Chi-squared assessments evaluated the occurrence of RCI-determined language decline. Independent sample t tests and MM-estimator robust regressions were used to assess the impact of clinical factors and fiber transection on RCI and change outcomes, respectively. RESULTS:Language-dominant and language-nondominant resections were treated separately for picture naming because postoperative outcomes were significantly different between these groups. In language-dominant hemisphere resections, greater surgical damage to the AF and IFOF was related to RCI decline at 3 months. Damage to the inferior frontal subfasciculus of the IFOF was related to change at 3 months. In language-nondominant hemisphere resections, increased MLF resection was associated with RCI decline at 3 months, and damage to the anterior subfasciculus was related to change at 3 months. Language-dominant and language-nondominant resections were treated as 1 cohort for semantic and phonemic fluency because there were no significant differences in postoperative decline between these groups. Postoperative seizure freedom was associated with an absence of significant language decline 12 months after surgery for semantic fluency. DISCUSSION:We demonstrate a relationship between fiber transection and naming decline after temporal lobe resection. Individualized surgical planning to spare white matter fiber bundles could help to preserve language function after surgery.

Around 50% of patients undergoing frontal lobe surgery for focal drug-resistant epilepsy become seizure free post-operatively; however, only about 30% of patients remain seizure free in the long-term. Early seizure recurrence is likely to be caused by partial resection of the epileptogenic lesion, whilst delayed seizure recurrence can occur even if the epileptogenic lesion has been completely excised. This suggests a coexistent epileptogenic network facilitating ictogenesis in close or distant dormant epileptic foci. As thalamic and striatal dysregulation can support epileptogenesis and disconnection of cortico-thalamostriatal pathways through hemispherotomy or neuromodulation can improve seizure outcome regardless of focality, we hypothesize that projections from the striatum and the thalamus to the cortex may contribute to this common epileptogenic network.To this end, we retrospectively reviewed a series of 47 consecutive individuals who underwent surgery for drug-resistant frontal lobe epilepsy. We performed voxel-based and tractography disconnectome analyses to investigate shared patterns of disconnection associated with long-term seizure freedom. Seizure freedom after 3 and 5 years was independently associated with disconnection of the anterior thalamic radiation and anterior cortico-striatal projections. This was also confirmed in a subgroup of 29 patients with complete resections, suggesting these pathways may play a critical role in supporting the development of novel epileptic networks.Our study indicates that network dysfunction in frontal lobe epilepsy may extend beyond the resection and putative epileptogenic zone. This may be critical in the pathogenesis of delayed seizure recurrence as thalamic and striatal networks may promote epileptogenesis and disconnection may underpin long-term seizure freedom.

In preterm infants, germinal matrix hemorrhage, intraventricular hemorrhage (IVH) and resultant post-hemorrhagic hydrocephalus (PHH) are common and important determinants of long-term cognitive outcomes. The management of IVH and PHH has undergone an evolution over the past decades, with current paradigms involving treatment with initial temporising measures followed by definitive management (if necessary) at around term-equivalent age. In this chapter, we discuss these current paradigms, examining the evidence for key decision points and the different temporising measures and conclude by presenting our institutional treatment algorithm. In addition, we look to the future, covering novel treatments such as neuroendoscopic lavage which may be crucial in improving the long-term neurodevelopmental outcomes in these patients.

Introduction Drug-resistant focal epilepsy presents a significant morbidity burden globally, and epilepsy surgery has been shown to be an effective treatment modality. Therefore, accurate identification of the epileptogenic zone for surgery is crucial, and in those with unclear noninvasive data, stereoencephalography is required. Areas covered This review covers the history and current practices in the field of intracranial EEG, particularly analyzing how stereotactic image-guidance, robot-assisted navigation, and improved imaging techniques have increased the accuracy, scope, and use of SEEG globally. Expert Opinion We provide a perspective on the future directions in the field, reviewing improvements in predicting electrode bending, image acquisition, machine learning and artificial intelligence, advances in surgical planning and visualization software and hardware. We also see the development of EEG analysis tools based on machine learning algorithms that are likely to work synergistically with neurophysiology experts and improve the efficiency of EEG and SEEG analysis and 3D visualization. Improving computer-assisted planning to minimize manual input from the surgeon, and seamless integration into an ergonomic and adaptive operating theater, incorporating hybrid microscopes, virtual and augmented reality is likely to be a significant area of improvement in the near future.

Individuals with temporal lobe epilepsy (TLE) may have significant language deficits. Language capabilities may further decline following temporal lobe resections. The language network, comprising dispersed gray matter regions interconnected with white matter fibers, may be atypical in individuals with TLE. This review explores the structural changes to the language network and the functional reorganization of language abilities in TLE. We discuss the importance of detailed reporting of patient's characteristics, such as, left- and right-sided focal epilepsies as well as lesional and nonlesional pathological subtypes. These factors can affect the healthy functioning of gray and/or white matter. Dysfunction of white matter and displacement of gray matter function could concurrently impact their ability, in turn, producing an interactive effect on typical language organization and function. Surgical intervention can result in impairment of function if the resection includes parts of this structure-function network that are critical to language. In addition, impairment may occur if language function has been reorganized and is included in a resection. Conversely, resection of an epileptogenic zone may be associated with recovery of cortical function and thus improvement in language function. We explore the abnormality of functional regions in a clinically applicable framework and highlight the differences in the underlying language network. Avoidance of language decline following surgical intervention may depend on tailored resections to avoid critical areas of gray matter and their white matter connections. Further work is required to elucidate the plasticity of the language network in TLE and to identify sub-types of language representation, both of which will be useful in planning surgery to spare language function.

Objective The accuracy of tunneled external ventricular drain (EVD) placement has been shown to be similar among practitioners of varying experience, but this has not yet been investigated for bolt EVDs. Tunneled and bolt EVDs are distinct techniques, and it is unclear if conclusions regarding accuracy can be inferred from one method to the other. The goal of this study was to determine whether neurosurgical experience influences the accuracy of bolt EVD placement. Methods We performed a single-center retrospective analysis of accuracy of bolt EVD placement between 1st December 2018 and 31st May 2020, comparing the accuracy outcomes between three levels of training (junior trainees (JT); mid-grade trainees (MT); senior trainees/fellows (ST)). Accuracy was determined radiologically by two methods: Kakarla grade and by measuring the distance of the catheter tip to its optimal position (DTOP) at the foramen of Monro. Results Eighty-seven patients underwent insertion of bolt EVDs, of which n = 19 by JT, n = 40 by MT and n = 28 by ST, with a significant difference found between training grades in the median Kakarla grade (p = 0.0055) and in the accuracy of placement as per DTOP (p = 0.0168). Conclusions In contrast to previous published results on tunneled EVDs, we demonstrate that the accuracy of bolt EVD placement is dependent on neurosurgical experience. Our results draw awareness to the fact that the bolt EVD technique can represent a challenge for less experienced practitioners and underline the importance of dedicated training to support the safe insertion of bolt ventricular catheters.

BackgroundThere is currently no effective treatment for promoting regeneration of injured nerves in patients who have sustained injury to the central nervous system such as spinal cord injury. Chondroitinase ABC is an enzyme, which promotes neurite outgrowth and regeneration. It has shown considerable promise as a therapy for these conditions. The aim of the study is to determine if targeting chondroitinase ABC expression to the neuronal axon can further enhance its ability to promote axon outgrowth. Long-distance axon regeneration has not yet been achieved, and would be a significant step in attaining functional recovery following spinal cord injury.Methodology/principal findingsTo investigate this, neuronal cultures were transfected with constructs encoding axon-targeted chondroitinase, non-targeted chondroitinase or GFP, and the effects on neuron outgrowth and sprouting determined on substrates either permissive or inhibitory to neuron regeneration. The mechanisms underlying the observed effects were also explored. Targeting chondroitinase to the neuronal axon markedly enhances its ability to promote neurite outgrowth. The increase in neurite length is associated with an upregulation of β-integrin staining at the axonal cell surface. Staining for phosphofocal adhesion kinase, is also increased, indicating that the β-integrins are in an activated state. Expression of chondroitinase within the neurons also resulted in a decrease in expression of PTEN and RhoA, molecules which present a block to neurite outgrowth, thus identifying two of the pathways by which ChABC promotes neurite outgrowth.Conclusions / significanceThe novel finding that targeting ChABC to the axon significantly enhances its ability to promote neurite extension, suggests that this may be an effective way of promoting long-distance axon regeneration following spinal cord injury. It could also potentially improve its efficacy in the treatment of other pathologies, where it has been shown to promote recovery, such as myocardial infarction, stroke and Parkinson's disease.

OBJECTIVE Temporary CSF diversion through an external ventricular drain (EVD) comes with the risk of EVD-related infections (ERIs). The incidence of ERIs varies from 0.8% to 22%. ERIs increase mortality, morbidity, length of stay, and costs; require prolonged courses of antibiotics; and increase the need for subsequent permanent CSF diversion. The authors report the results of a quality improvement project designed to improve infection rates and EVD placement using simulation training in addition to a standardized perioperative care bundle. This project resulted not only in a decrease in ERIs, but also a significant improvement in surgical outcomes. METHODS A best-practice standardized perioperative approach and care bundle was approved by consensus among the senior neurosurgeons at the authors’ institution, and a standardized operative note was designed to encourage adherence to policy and improve documentation. This approach was adapted from the bundle previously described by Kubilay et al. Simulation workshops were introduced to teach safe sampling technique, administration of intrathecal drugs, and a standardized operative technique using the Rowena head surgical model. Effects of the interventions on placement, infection rates, and displacement were measured at two distinct time points over a 2-year period. RESULTS Baseline audits demonstrated satisfactory EVD placement in 74%, an infection rate of 8.5%, and displacement occurring in 20%. In the 2 years following the interventions, satisfactory placement improved to 96%, infection rate fell to 4.8%, and inadvertent displacement occurred in only 1.7%. CONCLUSIONS Simulation training and standardizing the perioperative care of patients requiring EVDs dramatically improved placement accuracy, reduced infection rates, and reduced EVD displacement rate.

BACKGROUND: The outcomes of microsurgery of previously coiled aneurysms have been poorly described, and little is known about the factors predictive of poor outcome. Here we aimed to identify predictors of poor outcome following microsurgery for previously coiled recurrent aneurysms. METHODS: In this retrospective cohort study of a prospectively maintained vascular database, we reviewed presentations, recurrent aneurysm measurements, surgery, and outcomes of microsurgical clipping of recurrent previously coiled intracranial aneurysms. RESULTS: Our series comprised 39 patients (mean age, 49 years; range, 22-70 years) who underwent microsurgical clipping of 40 previously coiled intracranial aneurysms. One patient suffered seizures, 1 patient experienced transient neurologic worsening, and 1 patient developed hyponatraemia, none of whom had long-term sequelae. Two patients sustained postoperative infarcts, for an overall incidence of permanent morbidity of 5.1%. There were no deaths or rebleeds on follow-up. In 3 patients, including the 2 patients with infarct and 1 patient with a transient deficit, an attempt was made to remove the coil ball. These patients had larger aneurysms (1106 mm(3) vs. 135 mm(3); P = 0.005), with larger coil balls (257 mm(3) vs. 52 mm(3); P = 0.01) and wider necks (7.09 mm vs. 2.69 mm; P = 0.02) but smaller remnant heights (1.59 mm vs. 1.99 mm; P = 0.04). They were also more likely to have prolapsing coil loops (3/3 vs. 3/27; P = 0.016). CONCLUSIONS: Our study demonstrates good clinical outcomes from microsurgical clipping of recurrent aneurysms. In the vast majority of cases, clips can be applied primarily. Coil ball removal is associated with increased morbidity, and thus should be considered only as a second-line option, with the likely need identified before the initiation of surgery.

Background The Medical Registrar role increasingly involves delivery of complex clinical care through management of the multidisciplinary team1. The General Internal Medicine (GIM) curriculum reflects this, through non-technical competencies. Currently, there is no consensus on how to deliver training for this effectively, but growing evidence supports the use of simulation-based education (SBE)2. Educational Programme We developed an innovative, inter-professional pilot simulation course for GIM Higher Specialty trainees, delivered across three sites in our region. A collaborative approach was used to develop scenario content, mapped to their curriculum. This approach ensured quality control as well as sharing of faculty and expertise during course dates. Data was collected online through pre and post-course questionnaires. Course attendance certificates were issued after survey completion in order to maximise response uptake. Participants rated their confidence in 8 non-technical domains, informed by the GIM curriculum and faculty review, before and after the course. This was statistically analysed using paired T-test. Free-text responses were analysed thematically using an inductive coding technique. Results Six course dates were carried out across three sites. There were 34 participants, with 29 completing feedback (85%). Analysis of confidence ratings showed improvement in scores after the course in all domains; all but one of these results were statistically significant (Table 1). Thematic analysis revealed a wide range of learning outcomes. Those that were centred around non-technical skills acquisition included development in leadership, flexibility in communication, macro and micro-situational awareness, team-working and specific strategies to manage challenging environments. Additionally, participants stated personal benefits including increased confidence and development of reflective practice, strengthened through peer-learning. Participants felt this course was specifically tailored to their needs. Reasons for this included levels of realism not seen on other courses, a shift in focus towards human factors training and non-technical content not formally taught elsewhere. Abstract O60 Table 1 Non-technical Skills Domain Mean Confidence Scores (Scale 0– 100) Pre-Course Mean Confidence Scores (Scale 0– 100) Post-Course P-Value (paired T test) Enter a new clinical care scenario and effectively communicate with colleagues 67.28 79.86 0.003 Take a leadership role in a clinical care situation 67.89 76.68 0.037 Lead a multidisciplinary team meeting and reach effective management plans 65.72 81.73 0.001 Manage an emergency clinical care scenario using time and resources efficiently 66 76.14 0.016 Manage complaints effectively with positive outcomes 70.33 78.45 0.043 Communicate clinical reasoning and management plans to patients and relatives effectively 67.33 78.73 0.055 Discuss treatment escalation plans and resuscitation decisions comprehensively and effectively with patients and relatives 59.44 80.09 0.0001 Understand the human factors that play a role in complex clinical care situations 61.89 82.65 0.0001 Conclusions GIM Higher Specialty trainees have a role that has become increasingly complex and demanding, with less time to learn1. SBE offers training in a realistic and safe environment, allowing participants to develop and enhance skills necessary for optimal patient care. The results of this pilot study suggest that a dedicated, curriculum-mapped, inter-professional simulation course can address the deficiencies in non-technical competency training for GIM trainees. This study provides a basis for the development of a GIM simulation programme across the deanery. Ultimately, this may be an important platform to aid trainees in dealing with the challenges of the Registrar role.

Introduction: Among the confirmed cases of hydrocephalus in the Middle East, there is no standardization of care or differentiation between various types of hydrocephalus.This is the first study in the Middle Eastern regions that aims at developing a hydrocephalus clinical protocol for appropriate standard of care.Methods: We used a well-established clinical protocol from Johns Hopkins University and adapted it to a locally relevant clinical context with the help of an interdisciplinary panel of experts.The final protocol included diagnostic radiology studies, lumbar punctures (LP) as indication for surgery in hydrocephalus patients, and standardized times for follow-up visits were scheduled for optimal management of care.Baseline and follow-up testing protocol included gait assessment scales [Tinetti Gait and Balance Scale, Timed Up and Go task (TUG)] and ICIQ Urinary Incontinence short form.Results: Key highlights were cultural and language barriers which resulted in editing the testing and measures for use within the region (ex.translation into Arabic, religious beliefs, and education levels were incorporated to modify protocols).Gender roles and space constraints restricted feasibility of gait testing and required invasive procedures (ex.TUG times could not be assessed in a public hallway for women and women demanded inpatient stays for LP). Conclusions:The study highlights the need to raise awareness and standardize clinical protocols for screening and treating NPH in the region.A critical analysis of issues related to the how and why of implementation, and in turn optimizing the appropriateness and relevance to the particular circumstances is essential.

Elective intraparenchymal intracranial pressure (ICP) monitoring is useful for the diagnosis and treatment of hydrocephalus and cerebrospinal fluid (CSF) disorders. This retrospective study analyzes median ICP and pulse amplitude (PA) recordings in neurosurgically naïve patients undergoing elective ICP monitoring for suspected CSF disorders.

Background There is very little reported in the literature about the relationship between modifications of bacterial proteins and their secretion by mammalian cells that synthesize them. We previously reported that the secretion of the bacterial enzyme Chondroitinase ABC by mammalian cells requires the strategic removal of at least three N-glycosylation sites. The aim of this study was to determine if it is possible to enhance the efficacy of the enzyme as a treatment for spinal cord injury by increasing the quantity of enzyme secreted or by altering its cellular location. Methodology/Principal findings To determine if the efficiency of enzyme secretion could be further increased, cells were transfected with constructs encoding the gene for chondroitinase ABC modified for expression by mammalian cells; these contained additional modifications of strategic N-glycosylation sites or alternative signal sequences to direct secretion of the enzyme from the cells. We show that while removal of certain specific N-glycosylation sites enhances enzyme secretion, N-glycosylation of at least two other sites, N-856 and N-773, is essential for both production and secretion of active enzyme. Furthermore, we find that the signal sequence directing secretion also influences the quantity of enzyme secreted, and that this varies widely amongst the cell types tested. Last, we find that replacing the 3'UTR on the cDNA encoding Chondroitinase ABC with that of β-actin is sufficient to target the enzyme to the neuronal growth cone when transfected into neurons. This also enhances neurite outgrowth on an inhibitory substrate. Conclusion/Significance Some intracellular trafficking pathways are adversely affected by cryptic signals present in the bacterial gene sequence, whilst unexpectedly others are required for efficient secretion of the enzyme. Furthermore, targeting chondroitinase to the neuronal growth cone promotes its ability to increase neurite outgrowth on an inhibitory substrate. These findings are timely in view of the renewed prospects for gene therapy, and of direct relevance to strategies aimed at expressing foreign proteins in mammalian cells, in particular bacterial proteins.