The value of linear and non-linear quantitative EEG analysis in paediatric epilepsy surgery: a machine learning approach.

Epilepsy surgery is effective for patients with medication-resistant seizures, however 20-40% of them are not seizure free after surgery. Aim of this study is to evaluate the role of linear and non-linear EEG features to predict post-surgical outcome. We included 123 paediatric patients who underwent epilepsy surgery at Bambino Gesù Children Hospital (January 2009-April 2020). All patients had long term video-EEG monitoring. We analysed 1-min scalp interictal EEG (wakefulness and sleep) and extracted 13 linear and non-linear EEG features (power spectral density (PSD), Hjorth, approximate entropy, permutation entropy, Lyapunov and Hurst value). We used a logistic regression (LR) as feature selection process. To quantify the correlation between EEG features and surgical outcome we used an artificial neural network (ANN) model with 18 architectures. LR revealed a significant correlation between PSD of alpha band (sleep), Mobility index (sleep) and the Hurst value (sleep and awake) with outcome. The fifty-four ANN models gave a range of accuracy (46-65%) in predicting outcome. Within the fifty-four ANN models, we found a higher accuracy (64.8% ± 7.6%) in seizure outcome prediction, using features selected by LR. The combination of PSD of alpha band, mobility and the Hurst value positively correlate with good surgical outcome.

Current challenges in focal epilepsy treatment: An Italian Delphi consensus.

BACKGROUND: Epilepsy, a globally prevalent neurological condition, presents distinct challenges in management, particularly for focal-onset types. This study aimed at addressing the current challenges and perspectives in focal epilepsy management, with focus on the Italian reality. METHODS: Using the Delphi methodology, this research collected and analyzed the level of consensus of a panel of Italian epilepsy experts on key aspects of focal epilepsy care. Areas of focus included patient flow, treatment pathways, controlled versus uncontrolled epilepsy, follow-up protocols, and the relevance of patient-reported outcomes (PROs). This method allowed for a comprehensive assessment of consensus and divergences in clinical opinions and practices. RESULTS: The study achieved consensus on 23 out of 26 statements, with three items failing to reach a consensus. There was strong agreement on the importance of timely intervention, individualized treatment plans, regular follow-ups at Epilepsy Centers, and the role of PROs in clinical practice. In cases of uncontrolled focal epilepsy, there was a clear inclination to pursue alternative treatment options following the failure of two previous therapies. Divergent views were evident on the inclusion of epilepsy surgery in treatment for uncontrolled epilepsy and the routine necessity of EEG evaluations in follow-ups. Other key findings included concerns about the lack of pediatric-specific research limiting current therapeutic options in this patient population, insufficient attention to the transition from pediatric to adult care, and need for improved communication. The results highlighted the complexities in managing epilepsy, with broad consensus on patient care aspects, yet notable divergences in specific treatment and management approaches. CONCLUSION: The study offered valuable insights into the current state and complexities of managing focal-onset epilepsy. It highlighted many deficiencies in the therapeutic pathway of focal-onset epilepsy in the Italian reality, while it also underscored the importance of patient-centric care, the necessity of early and appropriate intervention, and individualized treatment approaches. The findings also called for continued research, policy development, and healthcare system improvements to enhance epilepsy management, highlighting the ongoing need for tailored healthcare solutions in this evolving field.

Phase-amplitude coupling between low- and high-frequency activities as preoperative biomarker of focal cortical dysplasia subtypes.

OBJECTIVE: To evaluate whether ictal phase-amplitude coupling (PAC) between high-frequency activity and low-frequency activity could be used as a preoperative biomarker of Focal Cortical Dysplasia (FCD) subtypes. We hypothesize that FCD seizures present unique PAC characteristics that may be linked to their specific histopathological features. METHODS: We retrospectively examined 12 children with FCD and refractory epilepsy who underwent successful epilepsy surgery. We identified ictal onsets recorded with stereo-EEG. We estimated the strength of PAC between low-frequencies and high-frequencies for each seizure by means of modulation index. Generalized mixed effect models and receiver operating characteristic (ROC) curve analysis were used to test the association between ictal PAC and FCD subtypes. RESULTS: Ictal PAC was significantly higher in patients with FCD type II compared to type I, only on SOZ-electrodes (p < 0.005). No differences in ictal PAC were found on non-SOZ electrodes. Pre-ictal PAC registered on SOZ electrodes predicted FCD histopathology with a classification accuracy > 0.9 (p < 0.05). CONCLUSIONS: The correlations between histopathology and neurophysiology provide evidence for the contribution of ictal PAC as a preoperative biomarker of FCD subtypes. SIGNIFICANCE: Developed into a proper clinical application, such a technique may help improve clinical management and facilitate the prediction of surgical outcome in patients with FCD undergoing stereo-EEG monitoring.

Epilepsy in KBG syndrome.

AIM: To illustrate the epileptological and electroencephalographic (EEG) characteristics of a cohort of patients with KBG syndrome and epilepsy. METHOD: Clinical history, age at epilepsy onset, seizure types, EEG findings, duration of epilepsy, and response to therapies were retrospectively reviewed in 11 patients (three females, eight males) with KBG syndrome. RESULTS: All detected genetic mutations were pathogenic and affected the C-terminal region at exon 9 of ANKRD11. One patient had 16q24.3 microdeletion including the ANKRD11 gene. Mean age at onset was 67 months. Epilepsy type was focal in five patients and generalized in four. Two patients had developmental and epileptic encephalopathies. Seizure freedom was obtained after a period varying between 15 days and 6 years. INTERPRETATION: In our patients, epilepsy appeared to respond well to treatment and, in some cases, to be self-limiting. The molecular characteristics of our patients' genetic abnormalities did not point towards any specific epilepsy hot spot. Epilepsy should be considered in the diagnostic work-up of patients with KBG syndrome. WHAT THIS PAPER ADDS: Some of the epilepsy types of KBG syndrome appear to be self-remitting. The epilepsy phenotypes associated with KBG syndrome are quite variable.

Long-term efficacy of glycopyrrolate on sialorrhea in Goldenhar syndrome: a case report.

BACKGROUND: Goldenhar syndrome (GS) is a rare congenital disease characterized by impaired development of different facial structures and deformations of the teeth structures. Sialorrhea, which can cause difficulties in breathing and language impairment, is very common in GS and often difficult to treat. This case report highlights the short- and long-term importance of the therapeutic choice - glycopyrronium in oral solution - for the treatment of sialorrhea in children with poly-malformative syndrome, complicated by outcomes of post-hemorrhagic hydrocephalus. CASE PRESENTATION: We report the case of a 6-year-old child with GS, carrying a percutaneous endoscopic gastrostomy after tracheostomy. The child also presented developmental dysfunction of oral motor skills of feeding, complicated by severe sialorrhea, related to the maxillo-facial dysmorphism. Sialorrhea caused several respiratory tract infections and led to an increase in the care burden. Both the inoculations of botulinum toxin and the treatment with scopolamine transdermal patch have shown mild and transient efficacy. The therapeutic choice of glycopyrronium in oral solution was the most suitable for this patient, leading to long-term sialorrhea control. CONCLUSIONS: This clinical experience represents the first long-term efficacy and tolerability evaluation in using glycopyrrolate oral solution in treating drooling in children with GS. The reduction of drooling over time and the lack of clinically relevant adverse events have contributed to the decrease of respiratory tract infections, the development of oral motor skills, and determining a positive psycho-social impact on the patient's quality of life and her family.

Current role of surgery for tuberous sclerosis complex-associated epilepsy.

Tuberous sclerosis complex (TSC) is a rare multisystem, autosomal dominant neurocutaneous syndrome in which epilepsy is the most common of several neurological and psychiatric manifestations. Around two thirds of patients develop drug-resistant epilepsy for whom surgical resection of epileptogenic foci is indicated when seizures remain inadequately controlled following trial of two antiseizure medications. The challenge with presurgical and surgical approaches with patients with TSC is overcoming the complexity from the number of tubers and the multiplex epileptogenic network forming the epileptogenic zone. Data suggest that seizure freedom is achieved by 55%-60% of patients, but predictive factors for success have remained elusive, which makes for unconfident selection of surgical candidates. This article presents three different cases as illustrations of the potential challenges faced when assessing the suitability of TSC patients for epilepsy surgery.

Can Presurgical Interhemispheric EEG Connectivity Predict Outcome in Hemispheric Surgery? A Brain Machine Learning Approach.

OBJECTIVES: Hemispherotomy (HT) is a surgical option for treatment of drug-resistant seizures due to hemispheric structural lesions. Factors affecting seizure outcome have not been fully clarified. In our study, we used a brain Machine Learning (ML) approach to evaluate the possible role of Inter-hemispheric EEG Connectivity (IC) in predicting post-surgical seizure outcome. METHODS: We collected 21 pediatric patients with drug-resistant epilepsy; who underwent HT in our center from 2009 to 2020; with a follow-up of at least two years. We selected 5-s windows of wakefulness and sleep pre-surgical EEG and we trained Artificial Neuronal Network (ANN) to estimate epilepsy outcome. We extracted EEG features as input data and selected the ANN with best accuracy. RESULTS: Among 21 patients, 15 (71%) were seizure and drug-free at last follow-up. ANN showed 73.3% of accuracy, with 85% of seizure free and 40% of non-seizure free patients appropriately classified. CONCLUSIONS: The accuracy level that we reached supports the hypothesis that pre-surgical EEG features may have the potential to predict epilepsy outcome after HT. SIGNIFICANCE: The role of pre-surgical EEG data in influencing seizure outcome after HT is still debated. We proposed a computational predictive model, with an ML approach, with a high accuracy level.

Hemispherotomy in Infants with Hemimegalencephaly: Long-Term Seizure and Developmental Outcome in Early Treated Patients.

Hemimegalencephaly (HME) is a rare brain congenital malformation, consisting in altered neuronal migration and proliferation within one hemisphere, which is responsible for early onset drug-resistant epilepsy. Hemispherotomy is an effective treatment option for patients with HME and drug-resistant epilepsy. Surgical outcome may be variable among different surgical series, and the long-term neuropsychological trajectory has been rarely defined using a standardized neurocognitive test. We report the epileptological and neuropsychological long-term outcomes of four consecutive HME patients, operated on before the age of three years. All patients were seizure-free and drug-free, and the minimum follow-up duration was of five years. Despite the excellent post-surgical seizure outcome, the long-term developmental outcome is quite variable between patients, ranging from mild to severe intellectual disabilities. Patients showed improvement mainly in communication skills, while visuo-perceptive and coordination abilities were more impaired. Epileptological outcome seems to be improved in early treated patients; however, neuropsychological outcome in HME patients may be highly variable despite early surgery.

Opsoclonus-Myoclonus Syndrome in Children and Adolescents: A Therapeutic Challenge.

Opsoclonus-myoclonus syndrome (OMS) is a neurological non-fatal disease that usually responds to immunotherapies. However, the real challenge is to counteract the high frequency of relapses and long-term developmental sequelae. Since the OMS is extremely rare, a common consensus regarding therapeutic guidelines is still lacking. The goals of this study were to test whether ACTH was superior to other immunotherapies and to investigate whether an early treatment could improve the outcome. Sixteen children affected by OMS were retrospectively reviewed. Eight children had a neuroblastic tumor. The other eight patients were affected by non-paraneoplastic OMS. Overall, the most commonly used treatment was corticotherapy (n = 11). However, ACTH (n = 10), rituximab (n = 7), immunoglobulins (n = 4), cyclophosphamide (n = 3), and mycophenolate (n = 2) were also administered. ACTH was associated with a high percentage of patients who healed (80%) and, as a first-line therapy, was associated with a lower incidence of relapses. An early treatment was associated with a favorable long-term outcome. Long-term sequelae occurred in 42% of patients who were treated early and in all of those who were treated late. It is advisable for the affected children to be identified at an early time, as they may benefit from an early treatment. ACTH represents an effective treatment with a high probability of recovery and low rate of relapses.

The Role of KRAS Mutations in Cortical Malformation and Epilepsy Surgery: A Novel Report of Nevus Sebaceous Syndrome and Review of the Literature.

The rare nevus sebaceous (NS) syndrome (NSS) includes cortical malformations and drug-resistant epilepsy. Somatic RAS-pathway genetic variants are pathogenetic in NS, but not yet described within the brain of patients with NSS. We report on a 5-year-old boy with mild psychomotor delay. A brown-yellow linear skin lesion suggestive of NS in the left temporo-occipital area was evident at birth. Epileptic spasms presented at aged six months. EEG showed continuous left temporo-occipital epileptiform abnormalities. Brain MRI revealed a similarly located diffuse cortical malformation with temporal pole volume reduction and a small hippocampus. We performed a left temporo-occipital resection with histopathological diagnosis of focal cortical dysplasia type Ia in the occipital region and hippocampal sclerosis type 1. Three years after surgery, he is seizure-and drug-free (Engel class Ia) and showed cognitive improvement. Genetic examination of brain and skin specimens revealed the c.35G > T (p.Gly12Val) KRAS somatic missense mutation. Literature review suggests epilepsy surgery in patients with NSS is highly efficacious, with 73% probability of seizure freedom. The few histological analyses reported evidenced disorganized cortex, occasionally with cytomegalic neurons. This is the first reported association of a KRAS genetic variant with cortical malformations associated with epilepsy, and suggests a possible genetic substrate for hippocampal sclerosis.

Neuroimaging and genetic characteristics of malformation of cortical development due to mTOR pathway dysregulation: clues for the epileptogenic lesions and indications for epilepsy surgery.

Introduction: Malformation of cortical development (MCD) is strongly associated with drug-resistant epilepsies for which surgery to remove epileptogenic lesions is common. Two notable technological advances in this field are identification of the underlying genetic cause and techniques in neuroimaging. These now question how presurgical evaluation ought to be approached for 'mTORpathies.'Area covered: From review of published primary and secondary articles, the authors summarize evidence to consider focal cortical dysplasia (FCD), tuber sclerosis complex (TSC), and hemimegalencephaly (HME) collectively as MCD mTORpathies. The authors also consider the unique features of these related conditions with particular focus on the practicalities of using neuroimaging techniques currently available to define surgical targets and predict post-surgical outcome. Ultimately, the authors consider the surgical dilemmas faced for each condition.Expert opinion: Considering FCD, TSC, and HME collectively as mTORpathies has some merit; however, a unified approach to presurgical evaluation would seem unachievable. Nevertheless, the authors believe combining genetic-centered classification and morphologic findings using advanced imaging techniques will eventually form the basis of a paradigm when considering candidacy for early surgery.

Surgery for drug-resistant tuberous sclerosis complex-associated epilepsy: who, when, and what.

Tuberous sclerosis complex (TSC) is a multisystem genetic disorder associated with refractory early-onset epilepsy. Current evidence supports surgery as the intervention most likely to achieve long-term seizure freedom, but no specific guidelines are available on TSC pre-surgical workup. This critical review assesses which TSC patients are suitable for surgical treatment, when pre-surgical evaluation should start, and what degree of surgical resection is optimal for postsurgical outcome. We searched for publications from 2000 to 2020 in Pubmed and Embase using the terms "tuberous sclerosis," "epilepsy," and "epilepsy surgery". To evaluate postsurgical seizure outcome, we selected only studies with at least one year of follow-up. Overall, we collected data on 1,026 patients from 34 studies. Age at surgery ranged from one month to 54 years. Mean age at surgery was 8.41 years. Of the diagnostic non-invasive pre-surgical tools, MRI and video-EEG were considered most appropriate. Promising data for epileptogenic tuber detection is provided from invasive SEEG studies. Data on surgery and related outcome were available for 769 patients. Seizure freedom was seen in 64.4% of patients who underwent tuberectomy, 68.9% treated with lobectomy and 65.1% with multilobar resection. The most effective surgical approach was lobectomy, even though more recently tuberectomy associated with the resection of the perituberal area seems to be the best approach to reach seizure freedom. Published postsurgical seizure freedom rates in patients with TSC were between 65% and 75%, but reduced to 48%-57% over longer follow-up periods. Early surgery might positively affect neurodevelopmental trajectory in some patients, even though data on cognitive outcome are still to be confirmed with longitudinal studies. Considering the strong correlation between epilepsy duration and neurocognitive outcome, all patients with TSC ought to be referred early to a dedicated epilepsy centre for individually tailored pre-surgical evaluation by a multi-disciplinary epilepsy surgery team.

Basal Ganglia Dysmorphism in Patients With Aicardi Syndrome.

OBJECTIVE: Aiming to detect associations between neuroradiologic and EEG evaluations and long-term clinical outcome in order to detect possible prognostic factors, a detailed clinical and neuroimaging characterization of 67 cases of Aicardi syndrome (AIC), collected through a multicenter collaboration, was performed. METHODS: Only patients who satisfied Sutton diagnostic criteria were included. Clinical outcome was assessed using gross motor function, manual ability, and eating and drinking ability classification systems. Brain imaging studies and statistical analysis were reviewed. RESULTS: Patients presented early-onset epilepsy, which evolved into drug-resistant seizures. AIC has a variable clinical course, leading to permanent disability in most cases; nevertheless, some cases presented residual motor abilities. Chorioretinal lacunae were present in 86.56% of our patients. Statistical analysis revealed correlations between MRI, EEG at onset, and clinical outcome. On brain imaging, 100% of the patients displayed corpus callosum malformations, 98% cortical dysplasia and nodular heterotopias, and 96.36% intracranial cysts (with similar rates of 2b and 2d). As well as demonstrating that posterior fossa abnormalities (found in 63.63% of cases) should also be considered a common feature in AIC, our study highlighted the presence (in 76.36%) of basal ganglia dysmorphisms (never previously reported). CONCLUSION: The AIC neuroradiologic phenotype consists of a complex brain malformation whose presence should be considered central to the diagnosis. Basal ganglia dysmorphisms are frequently associated. Our work underlines the importance of MRI and EEG, both for correct diagnosis and as a factor for predicting long-term outcome. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with AIC, specific MRI abnormalities and EEG at onset are associated with clinical outcomes.

Benign Intracranial Hypertension Due to Hypoparathyroidism: A Case Report.

Objective: The objective of this study is to present the rare case of a young girl with idiopathic intracranial hypertension secondary to hypoparathyroidism. Background: Idiopathic intracranial hypertension is a neurological syndrome characterized by elevated intracranial pressure (> 25 cmH2O) in the absence of intracerebral abnormalities or hydrocephalus. The pathophysiology of idiopathic intracranial hypertension is unknown, and rare cases of idiopathic intracranial hypertension secondary to hypoparathyroidism have been described. It is supposed that hypocalcemia causes decrease in the absorption of cerebrospinal fluid in arachnoidal granulations. Methods: The workup of the girl with idiopathic intracranial hypertension and hypoparathyroidism included physical examination, blood tests, diagnostic imaging, and lumbar puncture. Results: We present a 9-year-old female patient who was hospitalized for headache associated with nausea and vomiting for 3 weeks. She underwent an ophthalmologic examination that revealed papilledema. Lumbar puncture revealed an opening pressure of 65 cm H2O; cerebrospinal fluid analysis and brain computed tomography scan were normal. The patient started taking acetazolamide. Blood tests revealed hypocalcemia associated with high phosphorus level and undetectable PTH hormone, which led us to suspect hypoparathyroidism. She had never had cramps, paraesthesias, or tetany. Chvostek's and Trousseau's signs were positive. In the neck ultrasonography, parathyroids were not visible. Oral supplementation with calcitriol and calcium was started. Headache, nausea, and vomiting immediately disappeared after the lumbar puncture, and the papilledema improved gradually. Conclusions: Several anecdotal cases of idiopathic intracranial hypertension secondary to hypoparathyroidism have been described. However, our case report is of particular interest, since the child did not present with typical neurological hypoparathyroidism symptoms. Therefore, we recommend that hypoparathyroidism should be included in diagnostic investigations on children with clinical findings of idiopathic intracranial hypertension, because clinical manifestations of hypoparathyroidism are variable and may involve almost all organ systems.

Neuronal Ceroid Lipofuscinosis: Potential for Targeted Therapy.

Neuronal ceroid lipofuscinosis (NCLs) is a group of inherited neurodegenerative lysosomal storage diseases that together represent the most common cause of dementia in children. Phenotypically, patients have visual impairment, cognitive and motor decline, epilepsy, and premature death. A primary challenge is to halt and/or reverse these diseases, towards which developments in potential effective therapies are encouraging. Many treatments, including enzyme replacement therapy (for CLN1 and CLN2 diseases), stem-cell therapy (for CLN1, CLN2, and CLN8 diseases), gene therapy vector (for CLN1, CLN2, CLN3, CLN5, CLN6, CLN7, CLN10, and CLN11 diseases), and pharmacological drugs (for CLN1, CLN2, CLN3, and CLN6 diseases) have been evaluated for safety and efficacy in pre-clinical and clinical studies. Currently, cerliponase alpha for CLN2 disease is the only approved therapy for NCL. Lacking is any study of potential treatments for CLN4, CLN9, CLN12, CLN13 or CLN14 diseases. This review provides an overview of genetics for each CLN disease, and we discuss the current understanding from pre-clinical and clinical study of potential therapeutics. Various therapeutic interventions have been studied in many experimental animal models. Combination of treatments may be useful to slow or even halt disease progression; however, few therapies are unlikely to even partially reverse the disease and a complete reversal is currently improbable. Early diagnosis to allow initiation of therapy, when indicated, during asymptomatic stages is more important than ever.

Early Onset Epilepsy Caused by Low-Grade Epilepsy-Associated Tumors and Focal Meningeal Involvement.

Background: Low-grade epilepsy-associated neuroepithelial tumors (LEATs) are a frequent etiology in pediatric patients with epilepsy undergoing surgery. Objective: To identify differences in clinical and post-surgical follow-up between patients with focal meningeal involvement (MI) and those without MI within our cohort of pediatric patients with LEATs. Methods: We retrospectively reviewed all pediatric patients (<18 y) who underwent epilepsy surgery between 2011 and 2017 at our hospital. Cohort inclusion required histological diagnosis of LEATs and post-surgical follow-up of ≥2 y. We subsequently stratified patients according to presence of neuroradiological MI. Results: We identified 37 patients: five with MI and 32 without. Half of patients (19) were drug sensitive at surgery; similar between groups. The group with MI differed mainly for age of epilepsy-onset (0.6 vs. 7.0 y) but not for epilepsy duration (0.9 vs. 1.5 y). Post-surgery radiological follow-up (median 4.0 y; IQR 2.8-5.0 y) did not indicate disease progression. Seizure outcome was excellent in both groups, with 34 patients overall being both drug- and seizure-free. Conclusions: Our study identified a new subgroup of LEATs with focal MI and excellent post-surgical outcome. Moreover, this highlights the effectiveness of early surgery in pediatric LEATs.

Autism and Epilepsy in Patients With Tuberous Sclerosis Complex.

Introduction: Individuals with Tuberous Sclerosis Complex (TSC) are at increased risk of developing both epilepsy and autism spectrum disorder (ASD), but the relationship between these conditions is little understood. We reviewed published reports to elucidate the relationship between ASD, epilepsy, and TSC, and to define the genetic and neurological risk factors. Methods: Articles (January 2004-May 2019) were identified via PubMed, EMBASE, and CENTRAL databases. Article inclusion required report on individuals with TSC-associated ASD and epilepsy with prevalence, odds ratio, or rate report on the comorbidity of ASD in epileptic patients due to TSC. Results: A total of 841 abstracts were identified in the original search. Thirty-six articles were included, which identified study populations, ASD measures used, and study confounders as bias factors. This review included 2,666 TSC patients, with a mean age of 15.9 years (range 1.94-30.3 years). The percentage of TSC patients with epilepsy and autism was 33.7%. Patients with TSC and autism showed more frequent seizures and earlier epilepsy onset than TSC patients without autism. ASD and intractable epilepsy were both predicted by a higher number of areas with dysplastic features revealed in brain MR scans. ASD, the onset of seizures in children <2 years of age, and >3 tubers have all been associated with an increased risk of refractory epilepsy in TSC patients. However, the direction of the relationship is not clear because a history of epilepsy, or infantile spasms in patients with TSC is also associated with an increased likelihood of ASD. Overall, 73.2% of patients carried TSC2 genetic variant and, among patients with TSC and autism, the percentage of TSC2 individuals was 85.6%. Conclusions: The complex interrelationship between TSC, autism, and epilepsy, coupled with limited knowledge on the neurobiological basis for the interrelationship, limits overall understanding and opportunities for management. The results of this review highlight the need for early identification and management to optimize favorable outcomes in the most vulnerable individuals with TSC. Regardless of whether studies are considered individually or collectively, interpretation is made difficult due to the differences between the studies, most notably between methods and diagnostic criteria used to assess intellectual ability.

Generalized tonic seizures with autonomic signs are the hallmark of SCN8A developmental and epileptic encephalopathy.

Developmental and epileptic encephalopathy (DEE) due to SCN8A gene variants is characterized by drug-resistant early onset epilepsy associated with severe intellectual disability. Different seizure types have been reported, and a sequence of autonomic manifestations such as brady-/tachycardia, irregular breathing, and cyanosis. Nevertheless, an exhaustive video-polygraphic documentation is still lacking. In this study, we reviewed the ictal electroencephalograms (EEGs) of five patients with SCN8A-DEE followed-up at the Neuroscience Department at Bambino Gesù Children's Hospital in Rome. We identified generalized tonic seizure as the major seizure type at epilepsy onset. Seizure severity could vary from subtle to marked clinical manifestations, depending from the extent and groups of muscles involved and association with autonomic modifications. We found autonomic signs in 80% of seizures in our cases, and we were able to identify a stereotyped sequence of ictal events for most of seizures. Autonomic signs occurred in rapid sequence: flushing of the face, sometimes associated with sialorrhea, bradycardia, and hypopnea appeared within the first 1-2 s. Tachycardia, polypnea, perioral cyanosis, and pallor occurred later in the course of the seizure. Generalized tonic seizures are rarely described in other genetic epileptic conditions of early infancy because of ion channel mutations, such as in DEE due to KCNQ2 or SCN2A gene mutations, where seizures are most frequently reported as focal to bilateral tonic. Therefore, generalized symmetric tonic seizures with autonomic signs can be considered a clinical hallmark for diagnosis of SCN8A-related DEE and relevant for therapeutic implications.

Outcome after hemispherotomy in patients with intractable epilepsy: Comparison of techniques in the Italian experience.

OBJECTIVE: The objective of the study was to evaluate clinical characteristics and outcome of hemispherotomy in children and adolescents with hemispheric refractory epilepsy in an Italian cohort of patients. METHODS: We retrospectively evaluated the clinical course and outcome of 92 patients with refractory epilepsy who underwent hemispherotomy in three Italian epilepsy centers between 2006 and 2016. Three different approaches for hemispherotomy were used: parasagittal, modified parasagittal, and lateral. RESULTS: Mean age at epilepsy onset was 1.8 ±â€¯2.51 years, and mean duration of epilepsy prior to surgery was 7.4 ±â€¯5.6 years. Mean age at surgery was 9.2 ±â€¯8.0 years. After a mean follow-up of 2.81 ±â€¯2.4 years, 66 of 90 patients (two lost from follow-up, 73.3%) were seizure-free (Engel class I). The etiology of epilepsy was related to acquired lesions (encephalomalacia or gliosis) in 44 patients (47.8%), congenital malformations (cortical dysplasia, hemimegalencephaly, other cortical malformations) in 38 (41.3%), and progressive conditions (Rasmussen or Sturge-Weber syndrome) in 10 patients (10.9%). Regarding seizure outcome, we could not identify statistically significant differences between vertical and lateral approaches (p = 0.154). Seizure outcome was not statistically different in patients with congenital vs acquired or progressive etiologies (p = 0.43). Acute postoperative seizures (APOS) correlated with poor outcome (p < 0.05). On multivariate analysis, presurgical focal to bilateral tonic-clonic seizures (Odds Ratio (OR) = 3.63, 95% Confidence Interval (CI): 1.86-15.20, p = 0.048) independently predicted seizure recurrence. Twenty-one patients (22.8%) exhibited postoperative complications, with no unexpected and persistent neurological deficit. More than 50% of the patients completely tapered drugs. SIGNIFICANCE: Our data confirm hemispherotomy to be a safe and effective procedure in patients with drug resistant epilepsies due to hemispheric lesions. Presurgical focal to bilateral tonic-clonic seizures are the strongest predictor of seizure recurrence after surgery, independently from the type of hemispherotomy.

Clinical Features of Pediatric Idiopathic Intracranial Hypertension and Applicability of New ICHD-3 Criteria.

Idiopathic intracranial hypertension (IIH) is characterized by intracranial pressure >28 cmH2O in the absence of identifiable causes. Aim of this paper is to describe the clinical phenotype of pediatric IIH and to analyze the applicability of ICHD-3 criteria in comparison to the ICHD-2. We conducted a retrospective analysis of full clinical data of pediatric patients diagnosed with IIH between January 2007 and June 2018. Diagnostic evaluation included neuroimaging (all patients) and ultrasound-based optic nerve sheath diameter measurement (9 patients). Diagnosis of IIH was verified according to both ICHD-2 and ICHD-3 criteria for headache attributed to IIH, to verify the degree of concordance. We identified 41 subjects with suspected IIH; 14 were excluded due a diagnosis of secondary IH or lack of data. We therefore selected 27 subjects (age 4-15 years, mean 11). All patients presented with headache and bilateral papilloedema. Headache was daily in 22% cases, with diffuse gravative pain in 41%. In 4%, pain was exacerbated by cough, stress or tension. The most common presentation symptoms, in addition to headache, were blurred vision or diplopia (70%), vomiting (33%), and dizziness (15%). Twenty patients (74%) were obese. In 6 patients (22%) neuroimaging showed empty sella. Optic nerve sheath distension was detected in 6 out of 9 patients. Regarding the applicability of the ICHD-2 criteria, 18/27 (71%) patients have criterion A; 24/27 (89%) criterion B; 27/27 (100%) criterion C; 27/27 (100%) criterion D. When the ICHD-3 criteria were used, 27/27 (100%) fitted criterion A; 24/27 (89%) criterion B; 27/27 (100%) criterion C; and 27/27 (100%) criterion D. Our study suggests that, as compared with the ICHD-2, the new ICHD-3 criteria for headache attributed to IIH are better satisfied by pediatric patients with IIH. This is mainly due to the fact that qualitative headache characteristics are no longer considered in ICHD-3. Although the risk of under-rating the symptom of headache in IIH should not be disregarded, in pediatric population headache characteristics are usually less defined than in adults and obtaining a precise description of them is often very difficult.