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The coronavirus disease 2019 (COVID-19) pandemic had widespread impact on health care systems globally-particularly services arranged around elective admission and attendance such as epilepsy monitoring units and home video-EEG telemetry (HVET). Here, we review the ongoing impacts of the pandemic on HVET services among several different providers who used different initial models of HVET. We discuss the features of HVET that led to success in providing continued diagnostic services to patients with epilepsy and related disorders and through retrospective audit of our services demonstrate the high diagnostic yield of HVET. We reflect on this unforeseen future and its implications for other diagnostic techniques and approaches.

The “epilepsy-dyskinesia” spectrum is increasingly recognized in neurogenetic and neurometabolic conditions. It can be challenging to diagnose because of clinical and genetic heterogeneity, atypical or nonspecific presentations, and the rarity of each diagnostic entity. This is further complicated by the lack of sensitive or specific biomarkers for most nonenzymatic neurometabolic conditions. Nevertheless, clinical awareness and timely diagnosis are paramount to facilitate appropriate prognostication, counseling, and management.This report describes a case of a teenage girl who had presented at 14 months with a protracted illness manifesting as gastrointestinal upset and associated motor and cognitive regression.A choreoathetoid movement disorder, truncal ataxia, and microcephaly evolved after the acute phase. Neurometabolic and inflammatory investigations, EEG, brain MRI, muscle biopsy (including respiratory chain enzyme studies), and targeted genetic testing were unremarkable. A second distinct regression phase ensued at 14 years consisting of encephalopathy, multifocal motor seizures, absent deep tendon reflexes and worsening movements, gut dysmotility, and dysphagia. Video EEGs showed an evolving developmental and epileptic encephalopathy with multifocal seizures and nonepileptic movements. MRI of the brain revealed evolving and fluctuating patchy bihemispheric cortical changes, cerebellar atrophy with signal change, mild generalized brain volume loss, and abnormal lactate on MR spectroscopy. The article discusses the differential diagnostic approach and management options for patients presenting with neurologic regression, encephalopathy, seizures, and hyperkinetic movements. It also emphasizes the utility of next-generation sequencing in providing a rapid, efficient, cost-effective way of determining the underlying etiology of complex neurologic presentations.

Anoxic-epileptic seizures (AES) are rare outcomes of common childhood reflex anoxic syncope that trigger a true epileptic seizure. The term AES was coined by Stephenson in 1983, to differentiate these events from convulsive syncopes and the more common reflex anoxic syncopes. A genetic susceptibility for AES has been postulated; but, its molecular basis has up to now been elusive. We report here two illustrative cases and show the association of de novo SCN8A variants and AES. One of them had focal or generalized seizures and autonomic symptoms triggered by orthostatism; the second had breath-holding spells triggered by pain or exercise leading to tonic-clonic seizures; both had repeatedly normal EEGs and a family history of reflex syncope. The data of three additional AES patients further suggest, for the first time, a link between SCN8A pathogenic variants and AES. The neurodevelopment of four patients was abnormal. Four of the five SCN8A mutations observed here were previously described in patients with seizure disorders. Seizures responded particularly well to sodium channel blockers. Our observation enriches the spectrum of seizures linked with SCN8A pathogenic variants.

ZMYND11 is the critical gene in chromosome 10p15.3 microdeletion syndrome, a syndromic cause of intellectual disability. The phenotype of ZMYND11 variants has recently been extended to autism and seizures. We expand on the epilepsy phenotype of 20 individuals with pathogenic variants in ZMYND11.\ud \ud \ud We obtained clinical descriptions of sixteen new and nine published individuals, plus detailed case history of two children. New individuals were identified through GeneMatcher, ClinVar and the European Network for Therapies in Rare Epilepsy (NETRE). Genetic evaluation was performed using gene panels or exome sequencing; variants were classified using American College of Medical Genetics (ACMG) criteria.\ud \ud \ud Individuals with ZMYND11 associated epilepsy fell into three groups: (i) atypical benign partial epilepsy or idiopathic focal epilepsy (n=8); (ii) generalised epilepsies/infantile epileptic encephalopathy (n=4); (iii) unclassified (n=8). Seizure prognosis ranged from spontaneous remission to drug resistant. Neurodevelopmental deficits were invariable. Dysmorphic features were variable. Variants were distributed across the gene and mostly de novo with no precise genotype-phenotype correlation.\ud \ud \ud ZMYND11 is one of a small group of chromatin reader genes associated in the pathogenesis of epilepsy, and specifically ABPE. More detailed epilepsy descriptions of larger cohorts and functional studies might reveal genotype-phenotype correlation. The epileptogenic mechanism may be linked to interaction with histone H3.3.

ImportanceStereoelectroencephalography (SEEG) is more frequently being used in the pre-surgical evaluation of children with focal epilepsy. Many factors affect the rate of identification of a definable seizure onset zone (SOZ) and subsequent seizure freedom following SEEG-guided epilepsy surgery, which have not been systematically examined in multi-centre studies.ObjectivesDetermine the rates and factors that predict (a) whether or not a definable putative SOZ was identified on SEEG and (b) subsequent seizure freedom following surgical intervention.DesignRetrospective cohort studySettingMulticentre study involving 6 of 7 UK Children’s Epilepsy Surgery Service centres that perform paediatric SEEG in the UK.ParticipantsAll children undergoing SEEG from 2014 - March 2019 were included. Demographic, non-invasive evaluation, SEEG and operative factors were collected retrospectively from patient records.Main OutcomesThe two main outcome measures were (a) whether or not a definable putative SOZ was identified on SEEG (binary yes/no outcome) and (b) subsequent seizure freedom following surgical intervention (Engel classification)FindingsOne hundred and thirty-five patients underwent 139 SEEG explorations using a total of 1767 electrodes. A definable SOZ was identified in 117 patients (85.7%); odds of successfully finding a SOZ were 6.4x greater for non-motor seizures compared to motor seizures (p=0.02) and 3.6x more if ≥ 4 seizures were recorded during SEEG (p=0.03). Of 100 patients undergoing surgical treatment, 47 (47.0%) had an Engel class I outcome at a median follow-up of 1.3 years; the only factor associated with outcome was indication for SEEG (p=0.03). SEEG was safe with one (0.7%) haematoma requiring surgical evacuation and no long-term neurological deficits as a result of the procedure.Conclusions and RelevanceThis large nationally representative cohort illustrates that, in these patients who may not have otherwise been offered resective surgery, SEEG-guided surgery can still achieve high rates of seizure freedom. Seizure semiology and the number of seizures recorded during SEEG are important factors in the identification of a definable SOZ and the indication for SEEG is an important factor in post-operative outcomes.

Video-electroencephalographic (EEG) monitoring is an essential tool in epileptology, conventionally carried out in a hospital epilepsy monitoring unit. Due to high costs and long waiting times for hospital admission, coupled with technological advances, several centers have developed and implemented video-EEG monitoring in the patient's home (home video-EEG telemetry [HVET]). Here, we review the history and current status of three general approaches to HVET: (1) supervised HVET, which entails setting up video-EEG in the patient's home with daily visiting technologist support; (2) mobile HVET (also termed ambulatory video-EEG), which entails attaching electrodes in a health care facility, supplying the patient and carers with the hardware and instructions, and then asking the patient and carer to set up recording at home without technologist support; and (3) cloud-based HVET, which adds to either of the previous models continuous streaming of video-EEG from the home to the health care provider, with the option to review data in near real time, troubleshoot hardware remotely, and interact remotely with the patient. Our experience shows that HVET can be highly cost-effective and is well received by patients. We note limitations related to long-term electrode attachment and correct camera placing while the patient is unsupervised at home, and concerns related to regulations regarding data privacy for cloud services. We believe that HVET opens significant new opportunities for research, especially in the field of understanding the many influences in seizure occurrence. We speculate that in the future HVET may merge into innovative new multisensor approaches to continuously monitoring people with epilepsy.

Purpose Paediatric Epilepsy surgery in the UK has recently been centralised in order to improve expertise and quality of service available to children. Video EEG monitoring or telemetry is a highly specialised and a crucial component of the pre-surgical evaluation. Although many Epilepsy Monitoring Units work to certain standards, there is no national or international guideline for paediatric video telemetry. Methods Due to lack of evidence we used a modified Delphi process utilizing the clinical and academic expertise of the clinical neurophysiology sub-specialty group of Children's Epilepsy Surgical Service (CESS) centres in England and Wales. This process consisted of the following stages I: Identification of the consensus working group, II: Identification of key areas for guidelines, III: Consensus practice points and IV: Final review. Statements that gained consensus (median score of either 4 or 5 using a five-point Likerttype scale) were included in the guideline. Results Two rounds of feedback and amendments were undertaken. The consensus guidelines includes the following topics: referral pathways, neurophysiological equipment standards, standards of recording techniques, with specific emphasis on safety of video EEG monitoring both with and without drug withdrawal, a protocol for testing patient's behaviours, data storage and guidelines for writing factual reports and conclusions. All statements developed received a median score of 5 and were adopted by the group. Conclusion Using a modified Delphi process we were able to develop universally-accepted video EEG guidelines for the UK CESS. Although these recommendations have been specifically developed for the pre-surgical evaluation of children with epilepsy, it is assumed that most components are transferable to any paediatric video EEG monitoring setting.

Objective The high prevalence and impact of neurodevelopmental comorbidities in childhood epilepsy are now well known, as are the increased risks and familial aggregation of reading disability (RD) and speech sound disorder (SSD) in rolandic epilepsy (RE). The risk factors for RD in the general population include male sex, SSD, and ADHD, but it is not known if these are the same in RE or whether there is a contributory role of seizure and treatment-related variables. Methods An observational study of 108 probands with RE (age range: 3.6–22 years) and their 159 siblings (age range: 1–29 years; 83 with EEG data) were singly ascertained in the US or UK through a proband affected by RE. We used a nested case–control design, multiple logistic regression, and generalized estimating equations to test the hypothesis of an association between RD and seizure variables or antiepileptic drug treatment in RE; we also assessed an association between EEG focal sharp waves and RD in siblings. Results Reading disability was reported in 42% of probands and 22% of siblings. Among probands, RD was strongly associated with a history of SSD (OR: 9.64, 95% CI: 2.45–37.21), ADHD symptoms (OR: 10.31, 95% CI: 2.15–49.44), and male sex (OR: 3.62, 95% CI: 1.11–11.75) but not with seizure or treatment variables. Among siblings, RD was independently associated only with SSD (OR: 4.30, 95% CI: 1.42–13.0) and not with the presence of interictal EEG focal sharp waves. Significance The principal risk factors for RD in RE are SSD, ADHD, and male sex, the same risk factors as for RD without epilepsy. Seizure or treatment variables do not appear to be important risk factors for RD in probands with RE, and there was no evidence to support interictal EEG focal sharp waves as a risk factor for RD in siblings. Future studies should focus on the precise neuropsychological characterization of RD in families with RE and on the effectiveness of standard oral-language and reading interventions.

The concept of epilepsy syndromes, introduced in 1989, was defined as “clusters of signs and symptoms customarily occurring together”. Definition of epilepsy syndromes based on electro-clinical features facilitated clinical practice and, whenever possible, clinical research in homogeneous groups of patients with epilepsies. Progress in the fields of neuroimaging and genetics made it rapidly clear that, although crucial, the electro-clinical description of epilepsy syndromes was not sufficient to allow much needed development of targeted therapies and a better understanding of the underlying pathophysiological mechanisms of seizures. The 2017 ILAE position paper on Classification of the Epilepsies recognized that “as a critical tool for the practicing clinician, epilepsy classification must be relevant and dynamic to changes in thinking”. The concept of “epilepsy syndromes” evolved, incorporating issues related to aetiologies and comorbidities. A comprehensive update (and revision where necessary) of the EEG diagnostic criteria in the light of the 2017 revised terminology and concepts was deemed necessary. Part 2 covers the neonatal and paediatric syndromes in accordance with the age of onset. [Published with educational EEG plates at www.epilepticdisorders.com].

Rational. The concept of epilepsy syndromes, introduced in 1989, was defined as “clusters of signs and symptoms customarily occurring together”. Definition of epilepsy syndromes based on electro-clinical features facilitated clinical practice and, whenever possible, clinical research in homogeneous groups of patients with epilepsies. Progress in the fields of neuroimaging and genetics made it rapidly clear that, although crucial, the electro-clinical description of epilepsy syndromes was not sufficient to allow much needed development of targeted therapies and a better understanding of the underlying pathophysiological mechanisms of seizures. The 2017 ILAE position paper on Classification of the Epilepsies recognized that “as a critical tool for the practicing clinician, epilepsy classification must be relevant and dynamic to changes in thinking”. The concept of “epilepsy syndromes” evolved, incorporating issues related to aetiologies and comorbidities. A comprehensive update (and revision where necessary) of the EEG diagnostic criteria in the light of the 2017 revised terminology and concepts was deemed necessary. Methods. The work was commissioned by the Neurophysiology Task Force of the ILAE Committee on the Diagnostic Methods. Diagnostic criteria and recording procedures were developed by group consensus, reached through an “informal”, internal decision-making process. Each working group member was allocated a number of syndromes, and a standard structured template was used. International literature was extensively reviewed. Results. We developed a simple diagnostic system that is applicable to all epilepsy syndromes which allows the physician (i) to rate the strength of EEG diagnosis (degree of diagnostic certainty) by weighting EEG findings in relation to the available clinical information or the specific clinical question, and ii) to suggest further EEG diagnostics where conclusive diagnostic evidence is lacking. We also propose a system of syndrome-specific recording protocols that, used with the relevant clinical presentation or specific clinical question, may maximize activation of epileptic discharges and ultimately help with standardization of EEG recording across departments, worldwide. Because recording methodology also depends on available resources, a two-tier system was developed to embrace clinical EEG services in resource-limited and industrialized countries. A clinical practice statement for each of the epilepsy syndromes discussed underscores the crucial role of the clinical information with regards to both the optimization of the EEG recording and mainly its meaningful interpretation. Part I covers Genetic (Idiopathic) generalized epilepsies and syndromes, Reflex epilepsies, structural and genetic focal (lobar) syndromes and Progressive Myoclonus Epilepsies [Published with educational EEG plates on www.epilepticdisorders.com].

Significance Recently, autoantibodies against NMDA receptors (NMDARs) were identified as a major cause of autoimmune encephalitis. They cause abnormalities in brain function often associated with significant changes in patients’ brain dynamics. Here we use computational modeling to identify how NMDAR dysfunction causes abnormalities in brain dynamics using patient EEGs and local field potential recordings in a mouse model of NMDAR-Ab encephalitis. NMDAR autoantibodies cause a specific shift in excitatory coupling within cortical circuits that places the circuits closer to pathological transitions between dynamic brain states. Because of the proximity to these phase transitions, otherwise benign fluctuations in neuronal coupling cause abnormal EEG responses in the presence of the antibodies. Our modeling results thus explain fluctuating abnormalities in brain dynamics observed in patients., NMDA-receptor antibodies (NMDAR-Abs) cause an autoimmune encephalitis with a diverse range of EEG abnormalities. NMDAR-Abs are believed to disrupt receptor function, but how blocking this excitatory synaptic receptor can lead to paroxysmal EEG abnormalities—or even seizures—is poorly understood. Here we show that NMDAR-Abs change intrinsic cortical connections and neuronal population dynamics to alter the spectral composition of spontaneous EEG activity and predispose brain dynamics to paroxysmal abnormalities. Based on local field potential recordings in a mouse model, we first validate a dynamic causal model of NMDAR-Ab effects on cortical microcircuitry. Using this model, we then identify the key synaptic parameters that best explain EEG paroxysms in pediatric patients with NMDAR-Ab encephalitis. Finally, we use the mouse model to show that NMDAR-Ab–related changes render microcircuitry critically susceptible to overt EEG paroxysms when these key parameters are changed, even though the same parameter fluctuations are tolerated in the in silico model of the control condition. These findings offer mechanistic insights into circuit-level dysfunction induced by NMDAR-Ab.

Purpose To describe the development and implementation of video EEG telemetry (VT) in the patient's home (home video telemetry, HVT) in a single centre. Methods HVT met the UK Medical Research Council definition of a complex intervention, and we used its guidance to evaluate the process of piloting, evaluating, developing and implementing this new clinical service. The first phase was a feasibility study, comparing inpatient VT (IVT) with HVT in a test–retest design ( n =5), to assess data quality and yield of clinically relevant events. The second phase was a pre-implementation study ( n =8), to examine acceptability and satisfaction as well as the costs of IVT and HVT. Subsequently, we implemented the service, and reviewed the outcomes of the first 34 patients. Results The feasibility study found no difference in the quality of recording or clinical yield between IVT and HVT. The pre-implementation study showed excellent patient satisfaction. We also discuss the findings of the main stakeholder survey (consultants and technicians). Our economic modelling demonstrates a clear financial superiority of HVT over IVT. Conclusion Our findings show that diagnostic HVT for seizure classification and polysomnographies can be carried out safely in the patients' home and poses no security risks for staff. HVT can be effectively integrated into an existing tertiary care service as a routine home or community-based procedure. We hope to encourage other clinical neurophysiology departments and epilepsy centres to take advantage of our experience and consider adopting and implementing HVT, with the aim of a nationwide coverage.

Paediatric epilepsy is one of the most challenging aspects of clinical neurophysiology, as it is a dynamic entity in continuous evolution. A sound clinical understanding based on clinical history and examination combined with the ability to interpret paediatric electroencephalogram (EEG) is imperative prior to considering a diagnosis of epilepsy in children. A multidisciplinary approach involving regular communication between the referring physician, paediatric neurophysiologist, neuroradiologist, and geneticist is helpful as the child grows and the epilepsy becomes apparent. In a clinical setting, the primary aim is to diagnose seizure type(s) and distinguish it from the multitude of conditions that mimic epilepsy. The secondary aim is to define the electroclinical syndrome and aetiology, where possible, to guide treatment and prognosis. . In this chapter, the major paediatric epilepsies will be described according to the age of presentation from neonatal period, infancy, childhood, and adolescence as this approach mirrors clinical practice.

Management of hereditary neuropathy with liability to pressure palsy (HNPP) is primarily conservative, aimed at preventing nerve injury by avoiding trauma or other potential aggravating factors. No pharmacological treatment is known to be beneficial. We describe two adolescents, one with HNPP (male; aged 15y) and another with a clinical picture suggestive of HNPP (genetically unconfirmed; female; aged 14y), who showed considerable improvement of their symptoms after receiving corticosteroid therapy. Both individuals were symptomatic for at least 5 months before the treatment. Following corticosteroids, both individuals demonstrated rapid improvement leading to near-complete recovery of muscle power. Clinical improvement after corticosteroid therapy has been reported in some individuals with other hereditary neuropathies. Our cases demonstrate that corticosteroid therapy may also be beneficial in individuals with HNPP who have a protracted or incomplete course of recovery.

In Rett syndrome (RS), acute life-threatening episodes (ALTEs) are usually attributed to epilepsy or autonomic dysfunction but they can represent a movement disorder (MD). We describe three girls with RS who experienced ALTEs from an early age. These were long considered epileptic until video-EEG in Patients 1 and 3 revealed their non-epileptic nature. A primary dystonic mechanism was suspected and Patients 1 and 2 were treated with Trihexyphenidyl with significantly reduced frequency of the ALTEs. Patient 3 died before Trihexyphenidyl was tried. Trihexyphenidyl in RS patients with similar presentations can modify the dystonia and prevent ALTEs.

Management of hereditary neuropathy with liability to pressure palsy (HNPP) is primarily conservative, aimed at preventing nerve injury by avoiding trauma or other potential aggravating factors. No pharmacological treatment is known to be beneficial. We describe two adolescents, one with HNPP (male; aged 15y) and another with a clinical picture suggestive of HNPP (genetically unconfirmed; female; aged 14y), who showed considerable improvement of their symptoms after receiving corticosteroid therapy. Both individuals were symptomatic for at least 5 months before the treatment. Following corticosteroids, both individuals demonstrated rapid improvement leading to near-complete recovery of muscle power. Clinical improvement after corticosteroid therapy has been reported in some individuals with other hereditary neuropathies. Our cases demonstrate that corticosteroid therapy may also be beneficial in individuals with HNPP who have a protracted or incomplete course of recovery.

In Rett syndrome (RS), acute life-threatening episodes (ALTEs) are usually attributed to epilepsy or autonomic dysfunction but they can represent a movement disorder (MD). We describe three girls with RS who experienced ALTEs from an early age. These were long considered epileptic until video-EEG in Patients 1 and 3 revealed their non-epileptic nature. A primary dystonic mechanism was suspected and Patients 1 and 2 were treated with Trihexyphenidyl with significantly reduced frequency of the ALTEs. Patient 3 died before Trihexyphenidyl was tried. Trihexyphenidyl in RS patients with similar presentations can modify the dystonia and prevent ALTEs.

Moyamoya disease is an idiopathic cerebral vasculopathy, which may be progressive or non-progressive. Non-idiopathic forms with an associated disease are called moyamoya-like syndrome. The electroencephalographic finding characteristically seen after hyperventilation in about 50% of children with cerebrovascular disease includes gradual frequency decrease and activation of amplitude of slow waves which appear after the disappearance or attenuation of ordinary build up. This is termed the "re-build up" phenomenon, which is rarely seen and therefore may be under-recognized. We present video telemetry during a transient ischaemic event of a child subsequently diagnosed with moyamoya-like syndrome. We highlight the potential for misdiagnosis of organic non-epileptic events. Hyperventilation during EEG should be avoided in children with known moyamoya disease.

A boy was born at 42 weeks’ gestation following 4 days of labor. Epidural anesthesia was used. Bilateral wrist drop was noted immediately after delivery (figure 1). Induration with localized erythema was seen symmetrically on the dorsal …

R. Singh , S. Jayapal , S. Goyal , H. Jungbluth , K. Lascelles * Department of Paediatric Neurology, Evelina Children’s Hospital, Guys and St Thomas’ NHS Foundation Trust, United Kingdom Neurophysiology Department, Evelina Children’s Hospital, Guys and St Thomas’ NHS Foundation Trust, United Kingdom Randall Division of Cell and Molecular Biophysics, King’s College London, United Kingdom Department of Basic and Clinical Neuroscience, IoPPN, King’s College London, United Kingdom