The Pediatric Epilepsy Surgery Interest Group (PESIG) under the auspice of the ISPN Research Committee: Availability of relevant technology and geographical distribution.

PURPOSE: Epilepsy surgery for pediatric drug-resistant epilepsy has been shown to improve seizure control, enhance patient and family QoL, and reduce mortality. However, diagnostic tools and surgical capacity are less accessible worldwide. The International Society Pediatric Neurosurgery (ISPN) has established a Pediatric Epilepsy Surgery Interest Group (PESIG), aiming to enhance global collaboration in research and educational aspects. The goals of this manuscript are to introduce PESIG and analyze geographical differences of epilepsy surgery and technology availability. METHODS: PESIG was established (2022) following an ISPN executive board decision. Using a standardized form, we surveyed the PESIG members, collecting and analyzing data regarding geographical distribution, and availability of various epilepsy treatment-related technologies. RESULTS: Two hundred eighty-two members registered in PESIG from 70 countries, over 6 continents, were included. We categorized the countries by GDP as follows: low, lower-medium, upper-medium, and high income. The most commonly available technology was vagus nerve stimulation 68%. Stereoelectroencephalography was available for 58%. North America had statistically significant greater availability compared to other continents. Europe had greater availability compared to Africa, Asia, and South (Latin) America. Asia had greater availability compared to Africa. High-income countries had statistically significant greater availability compared to other income groups; there was no significant difference between the other income-level subgroups. CONCLUSION: There is a clear discrepancy between countries and continents regarding access to epilepsy surgery technologies. This strengthens the need for collaboration between neurologists and neurosurgeons from around the world, to enhance medical education and training, as well as to increase technological availability.

Transcriptomic profiling of nonneoplastic cortical tissues reveals epileptogenic mechanisms in dysembryoplastic neuroepithelial tumors.

Low-grade dysembryoplastic neuroepithelial tumors (DNTs) are a frequent cause of drug-refractory epilepsy. Molecular mechanisms underlying seizure generation in these tumors are poorly understood. This study was conducted to identify altered genes in nonneoplastic epileptogenic cortical tissues (ECTs) resected from DNT patients during electrocorticography (ECoG)-guided surgery. RNA sequencing (RNAseq) was used to determine the differentially expressed genes (DEGs) in these high-spiking ECTs compared to non-epileptic controls. A total of 477 DEGs (180 upregulated; 297 downregulated) were observed in the ECTs compared to non-epileptic controls. Gene ontology analysis revealed enrichment of genes belonging to the following Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways: (i) glutamatergic synapse; (ii) nitrogen metabolism; (iii) transcriptional misregulation in cancer; and (iv) protein digestion and absorption. The glutamatergic synapse pathway was enriched by DEGs such as GRM4, SLC1A6, GRIN2C, GRM2, GRM5, GRIN3A, and GRIN2B. Enhanced glutamatergic activity was observed in the pyramidal neurons of ECTs, which could be attributed to altered synaptic transmission in these tissues compared to non-epileptic controls. Besides glutamatergic synapse, altered expression of other genes such as GABRB1 (synapse formation), SLIT2 (axonal growth), and PROKR2 (neuron migration) could be linked to epileptogenesis in ECTs. Also, upregulation of GABRA6 gene in ECTs could underlie benzodiazepine resistance in these patients. Neural cell-type-specific gene set enrichment analysis (GSEA) revealed transcriptome of ECTs to be predominantly contributed by microglia and neurons. This study provides first comprehensive gene expression profiling of nonneoplastic ECTs of DNT patients and identifies genes/pathways potentially linked to epileptogenesis.

Role of Altered Expression, Activity and Sub-cellular Distribution of Various Histone Deacetylases (HDACs) in Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis.

Histone deacetylases (HDACs) have been described to have both neurotoxic and neuroprotective roles, and partly, depend on its sub-cellular distribution. HDAC inhibitors have a long history of use in the treatment of various neurological disorders including epilepsy. Key role of HDACs in GABAergic neurotransmission, synaptogenesis, synaptic plasticity and memory formation was demonstrated whereas very less is known about their role in drug-resistant epilepsy pathologies. The present study was aimed to investigate the changes in the expression of HDACs, activity and its sub-cellular distribution in mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) patients. For this study, surgically resected hippocampal tissue specimens of 28 MTLE-HS patients and 20 hippocampus from post-mortem cases were obtained. Real-time PCR was done to analyse the mRNA expression. HDAC activity and the protein levels of HDACs in cytoplasm as well as nucleus were measured spectrophotometrically. Further, sub-cellular localization of HDACs was characterized by immunofluorescence. Significant upregulation of HDAC1, HDAC2, HDAC4, HDAC5, HDAC6, HDAC10 and HDAC11 mRNA were observed in MTLE-HS. Alterations in the mRNA expression of glutamate and gamma-aminobutyric acid (GABA) receptor subunits have been also demonstrated. We observed significant increase of HDAC activity and nuclear level of HDAC1, HDAC2, HDAC5 and HDAC11 in the hippocampal samples obtained from patients with MTLE-HS. Moreover, we found altered cytoplasmic level of HDAC4, HDAC6 and HDAC10 in the hippocampal sample obtained from patients with MTLE-HS. Alterations in the level of HDACs could potentially be part of a dynamic transcription regulation associated with MTLE-HS. Changes in cytoplasmic level of HDAC4, 6 and 10 suggest that cytoplasmic substrates may play a crucial role in the pathophysiology of MTLE-HS. Knowledge regarding expression pattern and sub-cellular distribution of HDACs may help to devise specific HDACi therapy for epilepsy.

Comparison of a bolt-connected external ventricular drain with a tunneled external ventricular drain - a narrative review and meta-analysis.

External ventricular drain (EVD) is one of the most commonly performed neurosurgical procedures. EVD can be associated with high rates of complications like misplacement, iatrogenic hemorrhage, and CSF infection. Several modifications have been proposed in the EVD insertion techniques to decrease the risk of these complications. Bolt-connected EVD, one of these modifications which involves insertion of a bolt in the burr hole, has been proposed to have better chances of optimal placement of EVD tip, lesser risk of CSF infection, and accidental pullout. A comprehensive search of different databases was performed to retrieve studies comparing the bolt-connected EVD with tunneled EVD and meta-analysis was done. Seven studies met inclusion criteria and were included in the meta-analysis. Our analysis revealed that bolt-connected EVD is associated with significantly better chances of optimal placement than traditional tunneled EVD (MH OR-1.65, 95% CI 1.14 to 2.40, p = 0.008). We also observed that bolt-connected EVD is associated with significantly decreased risk of CSF infection (MH OR-0.60, 95% CI 0.39 to 0.94, p = 0.026), EVD malfunction (MH OR-0.31, 95% CI 0.16 to 0.58, p = 0.0003), and accidental disconnection (MH OR-0.09, 95% CI 0.03 to 0.26, p < 0.0001) as compared to traditional tunneled EVD. The difference between the two techniques was not statistically significant for complications, multiple punctures done for insertion of EVD, iatrogenic intracranial, and need of reoperation. Bolt-connected external ventricular drain is associated with significantly more chances of optimal placement and lesser chances of accidental discontinuation and CSF infection than tunneled EVD. There was no statistically significant difference noted between the two techniques for multiple punctures done for insertion of EVD, iatrogenic intracranial hemorrhage and need of reoperation. However, most of the included studies were retrospective. Thus, the results from the meta-analysis should be interpreted with caution as further prospective high-quality studies are needed.

Challenges and prospects of neurosurgical teleconsultations in a developing country: a reality check.

OBJECTIVE: The adoption of telemedicine became a necessity during the COVID-19 pandemic because patients found commuting to be difficult owing to travel restrictions. Initially, audio-based teleconsultations were provided. Later, on the basis of the feedback of patients and caregivers, the authors started to provide video-based teleconsultations via WhatsApp. The authors subsequently surveyed the patients and caregivers to determine their satisfaction levels with telemedicine services. METHODS: An anonymized telephone survey of patients who had participated in teleconsultation was conducted with a structured questionnaire. The responses were analyzed and their correlations with the perceived benefits and limitations of audio and video teleconsultation were determined. RESULTS: Three hundred respondents were included in the first round of surveys, of whom 250 (83.3%) consented to video teleconsultation. Among the respondents who participated in both audio and video teleconsultations (n = 250), paired analysis showed that video teleconsultation was perceived as better in terms of providing easier access to healthcare services (p < 0.001), saving time (p < 0.001), and satisfaction with the way patient needs were conveyed to healthcare providers (p = 0.023), as well as in terms of adequacy of addressing healthcare needs (p < 0.001) and consequently providing a higher rate of overall satisfaction (p < 0.001). For both audio and video teleconsultation, overall patient satisfaction was significantly related to only previous exposure to WhatsApp. However, for video consultation, longer call duration (p = 0.023) was an important independent factor. Video teleconsultation was preferable to face-to-face consultation irrespective of educational status, but higher education was associated with preference for video teleconsultation. CONCLUSIONS: Both audio and video teleconsultation are viable cost-effective surrogates for in-person physical neurosurgical consultation. Although audio teleconsultation is more user-friendly and is not restricted by educational status, video teleconsultation trumps the former owing to a more efficient and satisfactory doctor-to-patient interface.

Altered expression of activating transcription factor 3 in the hippocampus of patients with mesial temporal lobe epilepsy-hippocampal sclerosis (MTLE-HS).

Aim of the study: Activating Transforming factor 3 (ATF3) is a stress induced gene and closely associated with neuro-inflammation while Transforming growth Factor Beta (TGFß) signalling is also reported to be involved in neuro-inflammation and hyper-excitability associated with drug resistant epilepsy. Animal model studies indicate the involvement of ATF3 and TGFß receptors to promote epileptogenesis. Human studies also show that TGFß signalling is activated in MTLE-HS. However, lack of studies on ATF3 and TGFßRI expression in MTLE-HS patients exists. We hypothesize that ATF3 and TGFßRI might be expressed in hippocampi of patients with MTLE-HS and playing role in epileptogenesis.Materials & methods: Protein expression of ATF3 and TGFßRI was performed by western blotting. Localisation of ATF3 was performed by immunohistochemistry and immunoflorescence.Results: Protein expression of ATF3 and TGFßRI was significantly up-regulated in hippocampi of patients as compared to controls. Also ATF3 IR was significantly expressed in hippocampi of patients and ATF3 was expressed predominantly in cytoplasm as compared to nucleus. No correlation was found between ATF3 expression and epilepsy duration and seizure frequency.Conclusions: ATF3 and TGFßRI are both important players in neuro-inflammation and might potentiate epileptogenesis in these patients.

The development and efficacy of a mobile phone application to improve medication adherence for persons with epilepsy in limited resource settings: A preliminary study.

OBJECTIVE: Persons with epilepsy (PWE), especially those with limited education backgrounds from developing countries, are challenged by complicated medication regimens, debilitating seizures, and stigmatization in their daily life. Consequently, it is difficult for physicians to ensure medication adherence. This study validates a novel mobile application which was hypothesized to increase medication adherence and self-management skills in PWE. Created by medical professionals, the application included behavioral and educational components and was built to be easy-to-understand for those of socio-economically disadvantaged backgrounds. METHODS: This was a parallel, two-armed randomized controlled trial in which a total of 96 participants were enrolled from a Neurology Outpatient Department into a control standard care group and a mobile application group that used the smartphone application (app) in addition to the standard medical treatment. The app was intuitive and easy to understand for those coming from a socio-economically disadvantaged background. Medication adherence and self-efficacy were assessed with the Morisky Green and Levine Scale (MGLS) and the Epilepsy Self Efficacy Scale (ESES). Patients were reassessed 12 weeks later. Change in seizure frequency following administration of the application was a secondary outcome. RESULTS: In an intent-to-treat analysis, the mobile application interventional group showed over a 60% increase in the proportion of medication adherence (P < 0.0001). The mean self-efficacy score for the mobile application group was increased from 269.5 to 289.75 (P < 0.0001). The control group showed no statistically significant increases in either the proportion adherent or mean self-efficacy scores. SIGNIFICANCE: This study demonstrated the statistically significant performance of a mobile application in improving medication adherence and self-management skills in Indian persons with epilepsy.

Epilepsy surgery in COVID times-a unique conundrum.

The COVID-19 pandemic has forced hospitals to prioritize admissions. Epilepsy surgeries have been postponed at most centers. As the pandemic continues with no definite end in sight in the near future, the question arises until when such patients should be denied appropriate treatment. A 12-year-old child with left-sided Rasmussen's encephalitis with drug refractory epilepsy (DRE) presented at the height of the pandemic, with worsening of seizure frequency from 4-5/day to 20/day, with new-onset epilepsia partialis continua. She demonstrated features of progressive cognitive decline. The pros and cons of operating during the pandemic were discussed with the parents by a multidisciplinary team. She underwent endoscopic left hemispherotomy. Postoperatively she became seizure free but developed hospital-acquired mild COVID infection for which she was treated accordingly. Chosen cases of severe DRE, as the one illustrated above, who are deemed to benefit from surgery by a multidisciplinary team of physicians, should be re-categorized into the most severe class of patients and scheduled for surgery as soon as possible. The risk benefit ratio of the seizures being mitigated by surgery on one hand and possibility of acquiring COVID infection during hospital stay has to be balanced and a decision made accordingly.

Spontaneous external rupture of hydrocephalus after fontanelle closure: a case report and review of literature.

We report a 2-year-old child with congenital hydrocephalus who presented with a frontal meningocoele due to ventriculo-subgaleal fistula secondary to hydrocephalus (internal rupture), which gradually ruptured spontaneously through the skin. This case is unique given its association with occipital encephalocele and is only the second case to present with external rupture beyond the age of 1 year. Further, the ventricles have ruptured through the skull, after the closure of anterior fontanelle, into the subgaleal space. It challenges the present understanding that external rupture occurs only through an open anterior fontanelle.

Posterior fixation for paediatric and adolescent unstable hangman's fracture: evolution to C1 sparing techniques.

PURPOSE: The aim was to study surgical outcomes in hangman's fractures in paediatric and adolescent patients and to demonstrate evolution in posterior surgery from C1-C2-C3 fusion to C1 sparing techniques. METHODS: Patients (aged ≤ 18 years) operated at a tertiary level centre between September 2011 to February 2018 with more than 1 year of follow-up were included. Neurological status, type of fracture, operating time, blood loss, follow-up, and complications were assessed. RESULTS: Nine patients were included, with mean age mean of 16.45 years, with a mean follow-up of 42.78 months. Six patients having neurological deficit showed improvement. Two patients, one having undergone C1-C3 lateral mass screw rod fixation (LMSF) and other had C2 pedicle screw with C3 LMSF, developed kyphosis for which fixation was further extended caudally. One patient with an old hangman's fracture with reabsorbed axis pedicle underwent C2 body screw along with C3-C4 pedicle screw rod fixation and C2 pedicle reconstruction. All patients showed evidence of postoperative fusion. CONCLUSION: Hangman's fractures in young patients can be successfully managed via posterior fixation. In our centre, we have evolved in the direction of motion preservation at C1 C2 joint, along with 3 column stable fixation of the C2 pedicle. C2 pedicle reformation has allowed motion preserving surgery in complex fracture types. Extension of construct till C4 in selected cases is important to prevent postoperative kyphosis.

Impact of various cervical surgical interventions in patients with Hirayama's disease-a narrative review and meta-analysis.

Hirayama disease (HD) is a relatively uncommon cause of lower cervical myelopathy. A number of surgical approaches have been described in patients with HD in literature. We reviewed the literature and did a systematic review and meta-analysis of the studies which presented the clinical outcome following surgical intervention in HD. A systematic search of literature was performed with the keywords "Surgical treatment in Hirayama Disease", "Surgical approach in Hirayama Disease" and "Hirayama disease surgery". Data related to clinical outcome following surgery was pooled to calculate the pooled proportion of clinical improvement following anterior and posterior surgical approach. Thirty-four articles met the inclusion criteria and were included in the final review. Altogether, there were 10 types of surgical procedures performed for Hirayama disease. The most commonly described surgical technique was anterior cervical discectomy and fusion with cervical plating. The pooled proportion of patients experiencing clinical improvement following all cervical approaches was 80% (95% confidence interval 76 to 84%). Pooled proportion was maximum for anterior cervical plating (96% (95% confidence interval 62 to 100%)) and minimum for ACDF without plating (57% (95% confidence interval 20 to 88%)). Subgroup analysis based on different surgical approaches was not significant (p value = 0.61). The pooled proportion of patients experiencing clinical improvement following anterior and posterior cervical approach was 80% (95% confidence interval 76 to 84%) and 81% (95% confidence interval 66 to 91%). The indications of surgical treatment in patients with HD include poor patient compliance for neck collar or rapidly progressing severe disease. Good results with more than 80% chances of clinical improvement have been reported following various anterior and posterior surgical approaches. However, there was no significant difference in the pooled outcome of different surgical approaches. Most common technique used in literature is anterior cervical discectomy and fusion with plating.

Surgery for Drug-Resistant Epilepsy in Children.

BACKGROUND: Neurosurgical treatment may improve seizures in children and adolescents with drug-resistant epilepsy, but additional data are needed from randomized trials. METHODS: In this single-center trial, we randomly assigned 116 patients who were 18 years of age or younger with drug-resistant epilepsy to undergo brain surgery appropriate to the underlying cause of epilepsy along with appropriate medical therapy (surgery group, 57 patients) or to receive medical therapy alone (medical-therapy group, 59 patients). The patients in the medical-therapy group were assigned to a waiting list for surgery. The primary outcome was freedom from seizures at 12 months. Secondary outcomes were the score on the Hague Seizure Severity scale, the Binet-Kamat intelligence quotient, the social quotient on the Vineland Social Maturity Scale, and scores on the Child Behavior Checklist and the Pediatric Quality of Life Inventory. RESULTS: At 12 months, freedom from seizures occurred in 44 patients (77%) in the surgery group and in 4 (7%) in the medical-therapy group (P<0.001). Between-group differences in the change from baseline to 12 months significantly favored surgery with respect to the score on the Hague Seizure Severity scale (difference, 19.4; 95% confidence interval [CI], 15.8 to 23.1; P<0.001), on the Child Behavior Checklist (difference, 13.1; 95% CI, 10.7 to 15.6; P<0.001), on the Pediatric Quality of Life Inventory (difference, 21.9; 95% CI, 16.4 to 27.6; P<0.001), and on the Vineland Social Maturity Scale (difference, 4.7; 95% CI, 0.4 to 9.1; P=0.03), but not on the Binet-Kamat intelligence quotient (difference, 2.5; 95% CI, -0.1 to 5.1; P=0.06). Serious adverse events occurred in 19 patients (33%) in the surgery group, including hemiparesis in 15 (26%). CONCLUSIONS: In this single-center trial, children and adolescents with drug-resistant epilepsy who had undergone epilepsy surgery had a significantly higher rate of freedom from seizures and better scores with respect to behavior and quality of life than did those who continued medical therapy alone at 12 months. Surgery resulted in anticipated neurologic deficits related to the region of brain resection. (Funded by the Indian Council of Medical Research and others; Clinical Trial Registry-India number, CTRI/2010/091/000525 .).

α7 nicotinic receptors contributes to glutamatergic activity in the hippocampus of patients with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS).

Hyperglutamatergic activity in the hippocampus is a major feature of patients with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). Here we investigated whether tonic α7 nicotinic receptor (nAChR) activity could contribute to enhanced glutamatergic activity in the hippocampus of patients with MTLE-HS. Results showed that frequency and amplitude of glutamatergic events recorded from pyramidal neurons in the hippocampal samples obtained from patients with MTLE-HS were altered by α7 nAChR antagonist, methyllycaconitine, suggesting α7 nAChRs may influence hyperexcitability in MTLE-HS.

Preparedness and guidelines for neurosurgery in the COVID-19 era: Indian perspective from a tertiary care referral hospital.

The COVID-19 pandemic has severely impacted healthcare systems globally. The need of the hour is the development of effective strategies for protecting the lives of healthcare providers (HCPs) and judicious triage for optimal utilization of human and hospital resources. During this pandemic, neurosurgery, like other specialties, must transform, innovate, and adopt new guidelines and safety protocols for reducing the risk of cross-infection of HCPs without compromising patient care. In this article, the authors discuss the current neurosurgical practice guidelines at a high-volume tertiary care referral hospital in India and compare them with international guidelines and global consensus for neurosurgery practice in the COVID-19 era. Additionally, the authors highlight some of the modifications incorporated into their clinical practice, including those for stratification of neurosurgical cases, patient triaging based on COVID-19 testing, optimal manpower management, infrastructure reorganization, evolving modules for resident training, and innovations in operating guidelines. The authors recommend the use of their blueprint for stratification of neurosurgical cases, including their protocol for algorithmic patient triage and management and their template for manpower allocation to COVID-19 duty, as a replicable model for efficient healthcare delivery.

Impact of frailty on surgery for glioblastoma: a critical evaluation of patient outcomes and caregivers' perceptions in a developing country.

OBJECTIVE: The authors aimed to evaluate the impact of age and frailty on the surgical outcomes of patients with glioblastoma (GBM) and to assess caregivers' perceptions regarding postdischarge care and challenges faced in the developing country of India. METHODS: This was a retrospective study of patients with histopathologically proven GBM from 2009 to 2018. Data regarding the clinical and radiological characteristics as well as surgical outcomes were collected from the institute's electronic database. Taking Indian demographics into account, the authors used the cutoff age of 60 years to define patients as elderly. Frailty was estimated using the 11-point modified frailty index (mFI-11). Patients were divided into three groups: robust, with an mFI score of 0; moderately frail, with an mFI score of 1 or 2; and severely frail, with an mFI score ≥ 3. A questionnaire-based survey was done to assess caregivers' perceptions about postdischarge care. RESULTS: Of the 276 patients, there were 93 (33.7%) elderly patients and 183 (66.3%) young or middle-aged patients. The proportion of severely frail patients was significantly more in the elderly group (38.7%) than in the young or middle-aged group (28.4%) (p < 0.001). The authors performed univariate and multivariate analysis of associations of different short-term outcomes with age, sex, frailty, and Charlson Comorbidity Index. On the multivariate analysis, only frailty was found to be a significant predictor for in-hospital mortality, postoperative complications, and length of hospital and ICU stay (p < 0.001). On Cox regression analysis, the severely frail group was found to have a significantly lower overall survival rate compared with the moderately frail (p = 0.001) and robust groups (p < 0.001). With the increase in frailty, there was a concomitant increase in the requirement for readmissions (p = 0.003), postdischarge specialist care (p = 0.001), and help from extrafamilial sources (p < 0.001). Greater dissatisfaction with psychosocial and financial support among the caregivers of severely frail patients was seen as they found themselves ill-equipped to provide postdischarge care at home (p < 0.001). CONCLUSIONS: Frailty is a better predictor of poorer surgical outcomes than chronological age in terms of duration of hospital and ICU stay, postoperative complications, and in-hospital mortality. It also adds to the psychosocial and financial burdens of the caregivers, making postdischarge care challenging.

Management and prognosis of acute traumatic cervical central cord syndrome: systematic review and Spinal Cord Society-Spine Trauma Study Group position statement.

PURPOSE: Spinal Cord Society (SCS) and Spine Trauma Study Group (STSG) established a panel tasked with reviewing management and prognosis of acute traumatic cervical central cord syndrome (ATCCS) and recommend a consensus statement for its management. METHODS: A systematic review was performed according to the PRISMA 2009 guidelines. Delphi method was used to identify key research questions and achieve consensus. PubMed, Scopus and Google Scholar were searched for corresponding keywords. The initial search retrieved 770 articles of which 37 articles dealing with management, timing of surgery, complications or prognosis of ATCCS were identified. The literature review and draft position statements were compiled and circulated to panel members. The draft was modified incorporating relevant suggestions to reach consensus. RESULTS: Out of 37 studies, 15 were regarding management strategy, ten regarding timing of surgery and 12 regarding prognosis of ATCCS. CONCLUSION: There is reasonable evidence that patients with ATCCS secondary to vertebral fracture, dislocation, traumatic disc herniation or instability have better outcomes with early surgery (< 24 h). In patients of ATCCS secondary to extension injury in stenotic cervical canal without fracture/fracture dislocation/traumatic disc herniation/instability, there is requirement of high-quality prospective randomized controlled trials to resolve controversy regarding early surgery versus conservative management and delayed surgery if recovery plateaus or if there is a neurological deterioration. Until such time decision on surgery and its timing should be left to the judgment of physician, deliberating on pros and cons relevant to the particular patient and involving the well-informed patient and relatives in decision making. These slides can be retrieved under Electronic Supplementary Material.

Controversies in the surgical management of congenital craniocervical junction disorders - A critical review.

INTRODUCTION: Congenital disorders of the craniovertebral junction (CVJ) include a wide range of conditions, such as Chiari malformation (CM), basilar Invagination (BI), and atlantoaxial dislocation (AAD). The objective of this paper is to critically review the literature related to the management of congenital CVJ disorders focusing on: the significant developments in the past (from anterior open ventral decompression to modern CVJ realignment); the diagnosis of CVJ instability; the role of atlantoaxial fixation without posterior fossa decompression in patients with tonsillar herniation and no evidence of CVJ instability; use of C1-2 inter-articular spacers and use of C1-2 interarticular spacers with intra-operative manipulations to correct BI with AAD along with its deformity. MATERIALS AND METHODS: We performed a review of articles showing up on PubMed database without time restriction. Articles were included according to the purpose of our review and selected by two authors (AFJ and PSC). RESULTS: CVJ instability may be inferred when there is atlantoaxial abnormal motion seen on dynamic studies, facet joint subluxation or severe symptomatic CVJ kyphosis; routine fixation of patients with CM without clear CCJ instability, while based on an interesting hypothesis, still requires further studies; use of C1-2 inter-articular spacers for re-establishing CVJ alignment is probably the most effective surgery for posterior CVJ realignment and reduction of AAD and BI, potentially avoiding the need for an open or endoscopic anterior odontoidectomy (AO); current development of deformity correcting surgeries and the measurement of joint indices to plan surgery have provided new strategies for treatment. CONCLUSION: We present a critical review of important new concepts involved in the surgical treatment of CVJ congenital disease.

Technical descriptions of four hemispherectomy approaches: From the Pediatric Epilepsy Surgery Meeting at Gothenburg 2014.

Hemispherectomy is a complex multistep procedure with a steep learning curve. Several surgical approaches have been developed, but each requires considerable practice to master. Four experienced pediatric neurosurgeons, who participated in the 2014 Gothenburg Pediatric Epilepsy Surgery Meeting, provided succinct technical summaries of four hemispherectomy approaches: modified functional hemispherectomy, peri-insular hemispherotomy, parasagittal hemispherotomy, and endoscopic-assisted hemispherotomy. No clinical or outcome data are included. Our intention is to reduce the slope and length of the learning curve for surgeons and to improve the understanding of the technical details of hemispherectomy surgery by nonsurgeonmembers of epilepsy teams.

Synaptic roles of cyclin-dependent kinase 5 & its implications in epilepsy.

There is an urgent need to understand the molecular mechanisms underlying epilepsy to find novel prognostic/diagnostic biomarkers to prevent epilepsy patients at risk. Cyclin-dependent kinase 5 (CDK5) is involved in multiple neuronal functions and plays a crucial role in maintaining homeostatic synaptic plasticity by regulating intracellular signalling cascades at synapses. CDK5 deregulation is shown to be associated with various neurodegenerative diseases such as Alzheimer's disease. The association between chronic loss of CDK5 and seizures has been reported in animal models of epilepsy. Genetic expression of CDK5 at transcriptome level has been shown to be abnormal in intractable epilepsy. In this review various possible mechanisms by which deregulated CDK5 may alter synaptic transmission and possibly lead to epileptogenesis have been discussed. Further, CDK5 has been proposed as a potential biomarker as well as a pharmacological target for developing treatments for epilepsy.

RNA-seq analysis of hippocampal tissues reveals novel candidate genes for drug refractory epilepsy in patients with MTLE-HS.

Array-based profiling studies have shown implication of aberrant gene expression patterns in epileptogenesis. We have performed transcriptome analysis of hippocampal tissues resected from patients with MTLE-HS using RNAseq approach. Healthy tissues from tumour margins obtained during tumour surgeries were used as non-epileptic controls. RNA sequencing was performed using standard protocols on Illumina HiSeq 2500 platform. Differential gene expression analysis of the RNAseq data revealed 56 significantly regulated genes in MTLE patients. Gene cluster analysis identified 3 important hubs of genes mostly linked to, neuroinflammation and innate immunity, synaptic transmission and neuronal network modulation which are supportive of intrinsic severity hypothesis of pharmacoresistance. This study identified various genes like FN1 which is central in our analysis, NEUROD6, RELN, TGFßR2, NLRP1, SCRT1, CSNK2B, SCN1B, CABP1, KIF5A and antisense RNAs like AQP4-AS1 and KIRREL3-AS2 providing important insight into the understanding of the pathophysiology or genomic basis of drug refractory epilepsy due to MTS.