Emerging Trends in the Management of Cryptogenic Epilepsy

Cryptogenic epilepsy, accounting for ~40% of adult-onset epilepsies and a lesser proportion in paediatrics, is defined as epilepsy of presumed symptomatic nature in which the cause has not been identified. It has a higher prevalence of refractory seizures when compared to those with idiopathic epilepsy (40 vs. 26%). These patients are usually treated with multiple anti-epileptic drugs, yet the total number of which used is inversely proportional to their efficacy. Moreover, these children may have significantly worse behavioural problems and can result in substantial cognitive impairments when older. Luckily, the number of cryptogenic epilepsy cases is diminishing due to better diagnostic abilities in recent years. We aim to divide this chapter into three parts. First, we hope to discuss our working algorithm and explain the use and advantages of different imaging modalities including high-field 3-Tesla MRI with morphological analysis for accurate localisation of the epileptogenic foci. We shall then elaborate the concept of the epileptogenic circuit and explore the selection criteria for more invasive approaches, such as depth electrodes and SEEG. Last but not the least, we aim to discuss the surgical treatments, including VNS and DBS, and their outcomes in these patients

Epileptogenic zone, electrode location and clinical outcome in hippocampal electrical stimulation for mesial temporal lobe epilepsy : a correlation study

Objectif : Etudier les résultats cliniques du traitement de patients atteints pai- une épilepsie mésiale du lobe temporal (MTLE) réfractaire, par stimulation cérébrale profonde (DBS) de l'hippocampe, en fonction de l'emplacement de l'électrode. Méthodes : Huit patients atteints de MTLE implantés dans l'hippocampe et stimulés par DBS à haute fréquence ont été inclus dans cette étude. Cinq ont subi des enregistrements invasifs avec des électrodes profondes dans le but d'estimer la localisation du foyer ictal avant de procéder à une DBS chronique. La position des contacts actifs de l'électrode a été mesurée en utilisant une imagerie post-opératoire. Les distances par rapport au foyer ictal ont été calculées, et les structures hippocampiques influencées par la stimulation ont été identifiées au moyen d'un atlas neuro-anatomique. Ces deux paramètres ont été corrélés avec la réduction de la fréquence d'apparition des crises. Résultats : Les distances entre la localisation estimée des contacts actifs de l'électrode et le foyer ictal étaient respectivement 11.0 +/- 4.3 ou 9.1 +/- 2.3 mm pour les patients présentant une réduction de > 50% ou < 50% de la fréquence des crises. Chez les patients (N = 6) montrant une réduction de > 50% de la fréquence des crises, 100% avaient des contacts actifs situés à < 3 mm du subiculum (p < 0,05). Les 2 patients ne répondant pas au traitement étaient stimulés par des contacts situés à > 3mm du subiculum. Conclusion : La diminution de l'activité épileptogène induite par DBS sur l'hippocampe dans les cas de MTLE réfractaires : 1) ne semble pas directement liée à la proximité des contacts actifs de l'électrode au foyer ictal déterminé par les enregistrements invasifs ; 2) pourrait être obtenue par une neuro-modulation du subiculum

Surgical management of epilepsy

The fact that epilepsy can be cured or ameliorated with surgery is an often neglected and overlooked aspect of modern management. Epilepsy affects almost 50 million people worldwide. One-third of people who suffer from epilepsy are refractory to  medication alone. It is this group of patients who may benefit from epilepsy surgery, which can be divided into three main categories, i.e. resection procedures, disconnection procedures, and neuromodulation procedures. The goal of surgery in epilepsy is to remove the epileptogenic region from the brain, or to disconnect it and thereby prevent spread to other parts of the brain. In cases where this is not possible owing to the location of the epileptic focus, certain neuromodulation techniques may benefit the patient. Successful outcomes of epilepsy surgery techniques vary from 50% to 80% in rendering patients free of their epilepsy; many more patients can expect improvement in the severity or frequency of their disabling seizures. The outcome depends on factors such as age, location of the epileptogenic zone, histology and cause of the seizures. Patients undergo a detailed and prolonged work-up to determine candidacy and to decide on the safest technique that will lead to the best outcomes. An experienced team should perform the surgery. This team should consist of multiple members who can attend to the medical, social,  psychological and reintegration needs of the patient before and after surgery

Topics in Neuromodulation Treatment

"Topics in Neuromodulation Treatment" is a book that invites to the reader to make an update in this important and well-defined area involved in the Neuroscience world. The book pays attention in some aspects of the electrical therapy and also in the drug delivery management of several neurological illnesses including the classic ones like epilepsy, Parkinson's disease, pain, and other indications more recently incorporated to this important tool like bladder incontinency, heart ischemia and stroke. The manuscript is dedicated not only to the expert, but also to the scientist that begins in this amazing field. The authors are physicians of different specialties and they guarantee the clinical expertise to provide to the reader the best guide to treat the patient

Surgical management of epilepsy

The fact that epilepsy can be cured or ameliorated with surgery is an often neglected and overlooked aspect of modern management.Epilepsy affects almost 50 million people worldwide. One-third of people who suffer from epilepsy are refractory to medication alone. Itis this group of patients who may benefit from epilepsy surgery, which can be divided into three main categories, i.e. resection procedures,disconnection procedures, and neuromodulation procedures. The goal of surgery in epilepsy is to remove the epileptogenic region from thebrain, or to disconnect it and thereby prevent spread to other parts of the brain. In cases where this is not possible owing to the location ofthe epileptic focus, certain neuromodulation techniques may benefit the patient. Successful outcomes of epilepsy surgery techniques varyfrom 50% to 80% in rendering patients free of their epilepsy; many more patients can expect improvement in the severity or frequency oftheir disabling seizures. The outcome depends on factors such as age, location of the epileptogenic zone, histology and cause of the seizures.Patients undergo a detailed and prolonged work-up to determine candidacy and to decide on the safest technique that will lead to the bestoutcomes. An experienced team should perform the surgery. This team should consist of multiple members who can attend to the medical,social, psychological and reintegration needs of the patient before and after surgery

Getting the best outcomes from epilepsy surgery.

Neurosurgery is an underutilized treatment that can potentially cure drug-refractory epilepsy. Careful, multidisciplinary presurgical evaluation is vital for selecting patients and to ensure optimal outcomes. Advances in neuroimaging have improved diagnosis and guided surgical intervention. Invasive electroencephalography allows the evaluation of complex patients who would otherwise not be candidates for neurosurgery. We review the current state of the assessment and selection of patients and consider established and novel surgical procedures and associated outcome data. We aim to dispel myths that may inhibit physicians from referring and patients from considering neurosurgical intervention for drug-refractory focal epilepsies. Ann Neurol 2018;83:676-690

Intracranial stimulation for children with epilepsy

OBJECTIVES: To evaluate the efficacy of intracranial stimulation to treat refractory epilepsy in children. METHODS: This is a retrospective analysis of a pilot study on all 8 children who had intracranial electrical stimulation for the investigation and treatment of refractory epilepsy at King's College Hospital between 2014 and 2015. Five children (one with temporal lobe epilepsy and four with frontal lobe epilepsy) had subacute cortical stimulation (SCS) for a period of 20-161 h during intracranial video-telemetry. Efficacy of stimulation was evaluated by counting interictal discharges and seizures. Two children had thalamic deep brain stimulation (DBS) of the centromedian nucleus (one with idiopathic generalized epilepsy, one with presumed symptomatic generalized epilepsy), and one child on the anterior nucleus (right fronto-temporal epilepsy). The incidence of interictal discharges was evaluated visually and quantified automatically. RESULTS: Among the three children with DBS, two had >60% improvement in seizure frequency and severity and one had no improvement. Among the five children with SCS, four showed improvement in seizure frequency (>50%) and one chid did not show improvement. Procedures were well tolerated by children. CONCLUSION: Cortical and thalamic stimulation appear to be effective and well tolerated in children with refractory epilepsy. SCS can be used to identify the focus and predict the effects of resective surgery or chronic cortical stimulation. Further larger studies are necessary

Outcome of emergency neurosurgery in patients with refractory and super-refractory status epilepticus: a systematic review and individual participant data meta-analysis

BackgroundRefractory (RSE) and super-refractory status epilepticus (SRSE) are serious neurological conditions requiring aggressive management. Beyond anesthetic agents, there is a lack of evidence guiding management in these patients. This systematic review and individual participant data meta-analysis (IPDMA) seeks to evaluate and compare the currently available surgical techniques for the acute treatment of RSE and SRSE.MethodsA systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Individual Participant Data (PRISMA-IPD). Only patients who underwent surgery while in RSE and SRSE were included. Descriptive statistics were used to compare various subgroups. Multivariable logistic regression models were constructed to identify predictors of status epilepticus (SE) cessation, long-term overall seizure freedom, and favorable functional outcome (i.e., modified Rankin score of 0–2) at last follow-up.ResultsA total of 87 studies including 161 participants were included. Resective surgery tended to achieve better SE cessation rate (93.9%) compared to non-resective techniques (83.9%), but this did not reach significance (p = 0.071). Resective techniques were also more likely to achieve seizure freedom (69.1% vs. 34.4%, p = <0.0001). Older age at SE (OR = 1.384[1.046–1.832], p = 0.023) was associated with increased likelihood of SE cessation, while longer duration of SE (OR = 0.603[0.362–1.003], p = 0.051) and new-onset seizures (OR = 0.244[0.069–0.860], p = 0.028) were associated with lower likelihood of SE cessation, but this did not reach significance for SE duration. Only shorter duration of SE prior to surgery (OR = 1.675[1.168–2.404], p  = 0.0060) and immediate termination of SE (OR = 3.736 [1.323–10.548], p = 0.014) were independently associated with long-term seizure status. Rates of favorable functional outcomes (mRS of 0–2) were comparable between resective (44.4%) and non-resective (44.1%) techniques, and no independent predictors of outcome were identified.ConclusionOur findings suggest that emergency neurosurgery may be a safe and effective alternative in patients with RSE/SRSE and may be considered earlier during the disease course. However, the current literature is limited exclusively to small case series and case reports with high risk of publication bias. Larger clinical trials assessing long-term seizure and functional outcomes are warranted to establish robust management guidelines