Epilepticus In Slow Wave Sleep Research Articles

Proposed Pathway for the Utilization of Pediatric Ambulatory EEG.

The clinical utility of pediatric ambulatory-EEG (A-EEG) has been studied for decades, but limited information exists regarding which variables influence its utility. The authors aimed to evaluate clinical/EEG variables that may influence A-EEG yields and to develop a pathway for A-EEG utilization in children. Single-center retrospective review of A-EEGs performed from July 2019 to January 2021 in a tertiary referral center. The primary outcome was whether the A-EEG test successfully answered the referring physician's clinical question or influenced therapy. When it did, the A-EEG test was deemed useful. Clinical and EEG variables were assessed for their ability to predict utility. Further, the literature review generated 10 relevant prior studies whose details were used to generate a pathway for A-EEG utilization in children. One hundred forty-two A-EEG studies were included (mean age 8.8 years, 48% male patients, mean A-EEG duration 33.5 hours). Overall, A-EEG was considered useful in 106 children (75%) but heavily influenced by A-EEG indication. Specifically, it was deemed useful for 94% of patients evaluated for electrical status epilepticus in slow-wave sleep, 92% of those evaluated for interictal/ictal burden, and 63% of those undergoing spell classification. The test indication (P < 0.001), a diagnosis of epilepsy (P = 0.02), and an abnormal routine EEG (P = 0.04) were associated with A-EEG test utility, although the multivariate analysis confirmed the test indication as the only independent outcome predictor of A-EEG. Pediatric A-EEG is extremely useful for evaluating electrical status epilepticus in slow-wave sleep and interictal/ictal burden and is often helpful for spell classification. Among all clinical and EEG variables analyzed, the test indication was the only independent outcome predictor of obtaining a helpful A-EEG.

Generalized quasiperiodic epileptiform activity in sleep is associated with cognitive impairment in children with drug-resistant focal lesional epilepsy.

To evaluate the impact of generalized quasiperiodic epileptiform discharges ("hurdles") observed in non-rapid eye movement (NREM) sleep on cognitive function in children with intractable focal epilepsy. "Hurdles" pattern does not meet the criteria of the electrical status epilepticus in slow-wave sleep (ESES). In a retrospective analysis, 24 patients with "hurdles" and their 24 peers matched for demographic and epilepsy-related variables were compared in terms of neuropsychological domains and electroencephalography (EEG)-derived quantifiers. Both "hurdles" and controls were children between 2 and 19years of age who had intractable focal epilepsy evaluated as candidates of resective epilepsy surgery. Full-scale intelligence quotient/developmental quotient (FSIQ/DQ) (P=.002) and visuoconstructional skills (P=.004) were significantly lower in children with "hurdles" compared to controls. Patients with "hurdles" presented with higher interictal spike indexes in sleep (P<.001, median difference -0.9, 95% confidence interval [CI] -1.4, -0.6) and wakefulness (P<.001, median difference -0.3, 95% CI -0.5, -1). Relative time of sleep spindles in NREM sleep was significantly reduced (P<.001, median difference 0.1, 95% CI 0.0, 0.1) in the "hurdles" group. The time proportion of sleep spindles represented a significant positive (P=.008) and spike index of generalized spikes in sleep a significant negative explanatory variable (P=.004) of FSIQ/DQ scores. The proportion of seizure-free patients 2 years after epilepsy surgery did not differ significantly between the two groups (P=.19). Although the "hurdles" pattern does not fulfill the criteria of ESES, it is associated with a pronounced cognitive dysfunction. Disturbed sleep structure marked by reduced sleep spindles and generalized spiking in sleep is associated with worse cognitive performance. Despite having a generalized nature, we did not find a lower probability of postsurgical seizure freedom in patients with "hurdles" pattern.

Electrical status epilepticus during sleep in Mowat–Wilson syndrome

AimMowat–Wilson Syndrome (MWS) is a genetic rare disease. Epilepsy is present in 70–75% of Patients and an age-dependent electroclinical pattern has been described. Up to date, there are studies with overnight sleep EEGs, probably because of the severe intellectual disability (ID) and hyperactivity of these Patients.Our purpose was to verify the hypothesis that MWS Patients might have electrical status epilepticus in slow wave sleep (ESES pattern). MethodsA retrospective analysis of anamnestic and electrographic data was performed on 7 consecutive MWS Patients followed between 2007 and 2016. Only Patients with at least one overnight sleep EEG were included in the study. ResultsFive out of 7 Patients had overnight sleep EEG studies and were included in this study. All of them had an anterior ESES pattern with spike-and-wave index>85%. The architecture of sleep was abnormal. An ESES related regression of cognitive and motor functions with impact on daily activities (ESES-related syndrome) was demonstrated in 3 out of 5 (60%) Patients. In two Patients marked improvement of cognitive and motor performances was observed when the epileptiform activity during sleep was successfully controlled or it was spontaneously reduced. ConclusionsThe clinical significance of the ESES pattern is hard to assess in MWS Patients due to severe ID, but changing in behaviour or in motor and cognitive functions should mandate sleep EEG investigation and, if ESES is present, an appropriate treatment should be tried. Furthermore, overnight sleep EEG recordings, if regularly performed in the follow up, might help to understand if ESES pattern hampers the cognitive and communicative profile in MWS.

Abstracts from the Scottish Paediatric Society St Andrew's Day Paediatric Symposium: Royal College of Physicians of Edinburgh, Edinburgh, Friday 27 November 2015.

Summary: We present a family of three siblings. The older two had been given diagnoses of autism by the time the youngest presented with epileptic seizures. Investigation of the youngest sibling revealed a highly abnormal electroencephalogram which was characterised by electrical status epilepticus in slow wave sleep. The older siblings then had electroencephalograms which were also highly abnormal. All three children demonstrated an improvement in language and behaviour when treated with oral prednisolone. Index case: The index case, a five-year-old boy, presented in December 2014 with a nocturnal convulsive epileptic seizure lasting approximately 1 min. Four limb jerking was accompanied by drooling from the corner of his mouth. The following morning he was noted to be very different. He was not speaking and was described by his mother as being unusually “quiet and reserved.” A 24 h ambulatory electroencephalogram was arranged. This showed very frequent epileptic activity and electrical status epilepticus in slow wave sleep. He was treated with four weeks of oral prednisolone. He gradually regained his previous language ability. Repeat electroencephalogram two months later demonstrated a clear improvement, with no evidence of electrical status epilepticus in slow wave sleep. Older siblings: Older brother of the index case, aged nine, had been diagnosed with autism at the age of four. Having gained language skills up to the age of two years he went through a period of regression in speech and behaviour. Since then gradually gained language skills and was able to speak in three to four word sentences at the age of nine. Electroencephalogram at the age of nine was near identical to that of his younger brother. He was also treated with oral prednisolone. Both electroencephalogram and language ability improved markedly. An older sister of the index case, aged eight, had been diagnosed with autism at the age of five. At the age of two she could say several people’s names, several colours and could sing ‘twinkle twinkle little star’. She then lost all expressive language. Electroencephalogram at the age of seven was more abnormal than her brothers’ and also showed electrical status epilepticus in slow wave sleep. After treatment with oral prednisolone the electroencephalogram improved markedly and she started to say the names of her brothers. Message: We would like to use this case to highlight the importance of considering electrical status epilepticus in slow wave sleep as a cause of ‘autistic regression’. We would like to discuss the increasing evidence, particularly from genetic studies, supporting a theory of shared neurobiology between epilepsy and autism.

LONG TERM FOLLOW-UP OF LESIONAL AND NON-LESIONAL PATIENTS WITH ELECTRICAL STATUS EPILEPTICUS IN SLOW WAVE SLEEP.

A retrospective study has been done at the Bethesda Children's Hospital Epilepsy Center with those patients whose EEG records fulfilled in one or more records the criteria of electrical status epilepticus in slow wave sleep (ESES) pattern, occupying at least 75% of NREM sleep with bilateral discharges, and had detailed disease history and long term follow-up data, between 2000 and 2012. PATIENTS AND METHODS--Thirty-three patients (mean 11.1 +/- 4.2 years of age) were studied by 171 sleep EEG records. Sleep was recorded after sleep deprivation or during spontaneous sleep at least for one hour length of NREM. From the 492 EEGs, 171 sleep records were performed (average five/patient). Average follow-up time was 7.5 years. Eighty-two ESES records have been analyzed in 15 non-lesional and 18 lesional (11 with dysgenetic and seven with perinatal-asphyxic or vascular origin) patients. Variability of seizure types, seizure frequency and frequency of status epilepticus was higher in the lesional group. Impairment of the cognitive functions was moderate and partial in the non-lesional, while severely damaged in the lesional group. EEG records of 29 patients shawed unihemispherial spike fields with a perpendicular axis (in anterior, medial and posterior variants) to the Sylvian fissure, regardless their lesional or non-lesional origin. Only three (lone nonlesional and two lesional) patients had bilateral synchronous spike-wave discharges with bilateral symmetric frontocentral spike fields. The individual discharges of the sleep EEG pattern were very similar to the awake interictal records except their extension in time and field, their increased number, amplitude, and continuity of them and furthermore in the increased trans-hemispheral propagation and their synchronity. Assumed circuits involved in the pathomechanism of discharges during NREM sleep in ESES are discussed based on our findings.

Acetazolamide for electrical status epilepticus in slow-wave sleep.

Electrical status epilepticus in slow-wave sleep (ESES) is characterized by nearly continuous spike-wave discharges during non-rapid eye movement (REM) sleep. ESES is present in Landau-Kleffner syndrome (LKS) and continuous spike and wave in slow-wave sleep (CSWS). Sulthiame has demonstrated reduction in spike-wave index (SWI) in ESES, but is not available in the United States. Acetazolamide (AZM) is readily available and has similar pharmacologic properties. Our aims were to assess the effect of AZM on SWI and clinical response in children with LKS and CSWS. Children with LKS or CSWS treated with AZM at our institution were identified retrospectively. Pre- and posttherapy electroencephalography (EEG) studies were evaluated for SWI. Parental and teacher report of clinical improvement was recorded. Six children met criteria for inclusion. Three children (50%) demonstrated complete resolution or SWI <5% after AZM. All children had improvement in clinical seizures and subjective improvement in communication skills and school performance. Five of six children had subjective improvement in hyperactivity and attention. AZM is a potentially effective therapy for children with LKS and CSWS. This study lends to the knowledge of potential therapies that can be used for these disorders, which can be challenging for families and providers.

Encephalopathy with Electrical Status Epilepticus in Slow Wave Sleep – a review with an emphasis on regional (perisylvian) aspects

SUMMARYAim.The aim of this article is to review criticaly the Electrical Status Epilepticus in Slow Sleep (ESES) phenomenon from a neurophysiological mechanisms aspect as well as terminological and classification issues.Methods.The review includes all the relevant papers published during the last 43 years on the subject of ESES and Continous Spike – Wave in Sleep (CSWS).These papers were identified in various large databases via the internet.Rewiev and remarks.ESES/CSWS phenomena can be held as a common final pathway originating from different etiologies, including patients with early brain damage (probably involving thalamic structures), but also patients without structural pathology as in atypical evolution of idiopathic regional childhood hyperexcitability syndromes (with Rolandic epilepsy as a prototype). There are hints that genetic predisposition might be an important factor in the development of this process. The two large patient groups (lesional and non-lesional) show the same EEG evolution and encephalopathic cognitive consequences. The sleep EEG activation can be held as a common endophenotype. ESES represents an extreme sleep activation/potentiation of the local/regional interictal discharges, enhancing them in frequency, territorial extension, intra and trans-hemispherial propagation, synchrony and continuity. This process is most probably not identical with the development of bilateral spike-wave pattern in „generalized” epilepsies which involves primarily or secondarily the thalamocortical system as it had been explored by Gloor (1979) for idiopathic generalized rpilepsy and Steriade and Amzica (2003) for different types of generalized spike and wave discharges.Conclusions and syndromological embedding of ESES.In an overwhelming majority of the investigated cases, the maps of the single discharges constituting sleep activation are identical; with focal/regional interictal spikes followed by slow closing wave, as it is seen in childhood regional age dependent hyperexcitability syndromes (prototype of the centro-temporal spikes of Rolandic epilepsy). The main mechanism of the developing cognitive impairment is most probably the consequence of interference with plastic function of slow wave sleep by obliterating synaptic decline during sleep. Presently, the consensus and co-operative research is highly obstacled by the terminological chaos, the controversial definitions and views around this still striking and enigmatic phenomenon.

Clinical characteristics and outcome of children with electrical status epilepticus during slow wave sleep.

Background:Electrical status epilepticus in slow wave sleep (ESES) is a rare, age-related, self-limited disorder characterized as epilepsy with different seizure types, neuropsychological impairment in the form of global or selective regression of cognitive functions, motor impairment, and typical electroencephalographic (EEG) findings of continuous epileptic activity occupying 85% of nonrapid eye movement sleep.Aims:The aim is to examine the clinical and electrophysiological findings and treatment modalities of children with ESES and to evaluate the outcome of the disorder.Materials and Methods:Fourteen patients with a diagnosis of electrical status epilepticus during slow wave sleep and followed-up at least 2 years were included.Statistical Analysis:Pearson correlation test was used in the study.Results:Among the 14 patients, eight of them had normal mental development before ESES. Twelve of the patients mentioned cognitive impairment and decline in school performance during ESES. After ESES, seven patients had mental retardation in different severity. One of these patients was diagnosed with benign partial epilepsy of childhood with centrotemporal spikes and had normal intelligence quotient level prior to ESES. The diagnosis of ESES was made after newly occurred different seizure types in four of the patients while two of the previously known epileptic patients presented with only severe psychiatric impairment. Valproic acid and carbamazepine were the mostly frequently used drugs before the onset of ESES. After at least 2 years of follow-up, seven patients were seizure free, but still taking antiepileptic treatment. Five patients were seizure free, while two of them had ongoing seizures despite antiepileptic therapy.Conclusion:ESES should be kept in mind in children with unexplained regression or stagnation of development associated with seizures or not. Sleep EEGs should be performed for timely diagnosis, proper treatment and prevention of permanent cognitive impairment.

Neonatal thalamic hemorrhage is strongly associated with electrical status epilepticus in slow wave sleep

Thalamic hemorrhage has been associated with neonatal cerebral sinovenous thrombosis (CSVT), especially when the straight sinus is involved, and often presents with neonatal seizures. Early thalamic injury has previously been shown to predispose to epilepsy and electrical status epilepticus in slow wave sleep (ESES). The objective of this study was to assess the prevalence of sleep-induced epileptic electroencephalography (EEG) abnormalities and postneonatal epilepsy after neonatal thalamic hemorrhage associated with CSVT, in the absence of more widespread cerebral damage. Between 2003 and 2008 15 neonates were diagnosed with a thalamic hemorrhage due to suspected or proven CSVT. Neurodevelopment and the history of seizures were assessed at follow-up in the outpatient clinic in all 14 survivors (age 2-9years). Whole-night or sleep-deprived EEG recordings were obtained to assess the prevalence of interictal epileptiform activity (EA) and calculate a sleep-induced spike and wave index (SWI). Three children were diagnosed with classic ESES (SWI >85%). Two children had ESES spectrum disorder (SWI between 50% and 85%), and in two children significant sleep-induced epileptiform activity (SIEA) was noted (SWI between 25% and 50%). Two other children were diagnosed with focal epilepsy, in the absence of sleep-induced epileptiform EEG abnormalities. Five children (age 2-7years) had normal EEG recordings at follow-up. Deficits in neurodevelopment were seen significantly more often in children with ESES, ESES spectrum, or SIEA. Neonates with thalamic hemorrhage associated with straight sinus thrombosis, without evidence of more widespread cerebral damage, are at high risk of developing ESES (spectrum) disorder (35%), SIEA (14%), or focal epilepsy (14%). Electrographic abnormalities may already be present prior to recognition of cognitive deficits. Early diagnosis may guide parents and caregivers, and subsequent treatment may improve neurodevelopmental outcome. Routine annual sleep EEG recordings in children with neonatal thalamic injury following CSVT may improve recognition of ESES.

Treatment of Epileptic Encephalopathies

Epileptic encephalopathy is defined as a condition where the epileptic activity itself may contribute to the severe neurological and cognitive impairment seen, over and above that which would be expected from the underlying pathology alone. The epilepsy syndromes at high risk of this are a disparate group of conditions characterized by epileptic seizures that are difficult to treat and developmental delay. In this review, we discuss the ongoing debate regarding the significance of inter-ictal discharges and the impact of the seizures themselves on the cognitive delay or regression that is a common feature of these syndromes. The syndromes also differ in many ways and we provide a summary of the key features of the early-onset epileptic encephalopathies including Ohtahara and West syndromes in addition to later childhood-onset syndromes such as Lennox Gastaut and Doose syndromes. An understanding of the various severe epilepsy syndromes is vital to understanding the rationale for treatment. For example, the resolution of hypsarrhythmia in West syndrome is associated with an improvement in cognitive outcome and drives treatment choice, but the same cannot be applied to frequent inter-ictal discharges in Lennox Gastaut syndrome. We discuss the evidence base for treatment where it is available and describe current practice where it is not. For example, in West syndrome there is some evidence for preference of hormonal treatments over vigabatrin, although the choice and duration of hormonal treatment remains unclear. We describe the use of conventional and newer anti-epileptic medications in the various syndromes and discuss which medications should be avoided. Older possibly forgotten treatments such as sulthiame and potassium bromide also have a role in the severe epilepsies of childhood. We discuss hormonal treatment with particular focus on the treatment of West syndrome, continuous spike wave in slow wave sleep (CSWS)/electrical status epilepticus in slow wave sleep (ESES) and Landau Kleffner syndrome. The role of the ketogenic diet has in recent years come to the fore of the management of these severe epilepsies and we describe successful use in myoclonic astatic epilepsy, Lennox Gastaut syndrome and Dravet syndrome. It is important that resective epilepsy surgery is not ignored in the management of these children, particularly those with hemi-pathology who may present with ESES and respond well to hemispheric disconnection. Adjunctive and symptomatic surgical treatments such as vagal nerve stimulation and corpus callosotomy may improve seizure burden. Finally, it is vital that the identification and treatment of developmental, behavioural and psychiatric co-morbidities are not neglected and that a rational, holistic approach is taken to the management of epileptic encephalopathies.

A Review of Children with Electrical Status Epilepticus in Slow Wave Sleep (ESES) (P04.174)

Objective: To determine characteristics, treatment and outcome of children with electrical status epilepticus in slow wave sleep (ESES). Background ESES is a rare EEG finding associated with Landau Kleffner syndrome (LKS) and Continuous Spike Wave in Sleep syndrome (CSWS). These syndromes are potentially treatable causes of developmental regression. Design/Methods: All patients with ESES seen at Mayo Clinic 2007-2011 were retrospectively identified. All patients underwent detailed evaluation, neurological examination, and prolonged EEG monitoring during evaluation and follow up. Medical records, EEGs, and neuroimaging were reviewed to determine clinical presentation, treatment, and outcome. Results: 30 patients were identified. Average age at onset of regression was 5.4 years (range 13 months to 11 years). 6/30 patients met criteria for LKS. 24/30 patients met criteria for CSWS. Etiologies included unknown cause (14/30), symptomatic (16/30). Specific etiologies included thalamic injury (3), hydrocephalus (4), cortical dysplasia (3). EEG abnormalities in LKS were maximally present over the frontotemporal head regions; in CSWS, EEG abnormalities were more diffuse. Presenting symptoms included: regression of language, regression of motor skills, frontal lobe syndrome (inattention, impulsivity, difficulty with planning and sequencing activities), behavioral difficulties, autistic features, and decreased level of consciousness. 26/30 patients underwent treatment with followup at Mayo Clinic. Successful therapies include diazepam, corticosteroids, IVIG, ethosuximide, zonisamide, focal parietal resection, temporal lobectomy, although relapses did occur. Unsuccessful treatments include valproic acid, lamotrigine, levetiracetam, sulthiame, felbamate, deep brain stimulation, mycophenolate mofetil. 24/26 patients responded to treatment. 6/24 patients relapsed. 17/26 are currently in remission. Follow up time was 1.7 patient years. Conclusions: ESES is a rare but treatable cause of childhood developmental regression. It is important to screen children with seizures and regression for ESES as this is a treatable conditon. Effective treatments may include diazepam, prednisone, IVIG, ethosuximide, zonisamide, focal epilepsy surgery. Relapse is common, but terminal remission is possible. Disclosure: Dr. Martyanov has nothing to disclose. Dr. Wirrell has received research support from Mayo Foundation. Dr. Nickels has nothing to disclose.

Sleep spindle activity in double cortex syndrome: a case report

Cortical dysgenesis is increasingly recognised as a cause of epilepsy. We report a case with double cortex heterotopia and secondarily generalized seizures with a generalised spike wave pattern. During the course of the disease, the child developed electrical status epilepticus in slow wave sleep. From the first examination, sleep pattern revealed increased frequency and amplitude of spindle activity, more evident in anterior areas. The role of the thalamocortical pathway in increased sleep spindle activity is discussed with emphasis on the possible role of altered thalamocortical pathways in abnormal cortical migration. A strong suspicion of cortical dysgenesis may therefore be based on specific EEG sleep patterns.

Pediatric State of the Art Symposium

1 Ajay Gupta, and 2 Mohamad Mikati ( 1 Department of Neurology, Cleveland Clinic Foundation, Cleveland, OH ; and 2 Department of Neurology, American University of Beirut, Beirut, Lebanon )There is a unique, apparently heterogeneous, group of epilepsy syndromes in children that is characterized by sleep activation of the epileptiform abnormalities with nearly continuous sharp waves seen on the scalp EEG during sleep. These include commonly recognized childhood conditions such as Landau‐Kleffner syndrome (LKS), electrical status epilepticus in slow wave sleep (ESES), and benign rolandic epilepsy of childhood (BREC). Most of these children have a period of normal development and healthy childhood. Besides presenting with seizures that are often not too difficult to treat, these children have other major cognitive, behavioral and academic difficulties that are disproportionate to the burden of epilepsy and medications used to treat them. It is commonly believed that abnormal electrical activity in sleep per se leads to cognitive, behavioral, and academic difficulties in these children. However, the pathophysiological understanding of this phenomenon of sleep activation and its clinical implications are poorly understood. Moreover, there are also controversies regarding terminology, classification, and management of these disorders. Some experts believe that these conditions are distinct disease entities while others hypothesize that they may represent a spectrum of one condition. Similar sleep activation of epileptic discharges has also been reported in some other children with neuroimaging abnormalities in the deep gray nuclei. Some experts believe that the treatment with antiepileptic medications in these children should be titrated to the EEG response in sleep and not to the clinical response of seizures. It is unclear as to how often a sleep EEG should be done, and to what extent aggressive medical treatment and antiepileptic polytherapy be pursued. Use of steroids, recent success with high dose nightly benzodiazepine therapy, and surgical procedure like multiple subpial transactions in the insular regions continue to be controversial due to risk of serious side effects and modest benefits in reported anecdotal case reports and series. The focus of this symposium is to revisit these syndromes to: a) define the clinical spectrum of these conditions; b) formulate the best practices for management in the light of controversies in medical and surgical options; and c) discuss possible pathophysiological mechanisms underlying these disorders and probe future strategies for better treatment. Margret Shouse will show similarities between kindled epileptic kittens and sleep activation of EEG in children with these conditions. She will review the potential mechanisms and generators of EEG activity during sleep, discuss how the cognitive and behavioral sequelae may occur regardless of severe seizure burden. Edouard Hirsch will discuss the available clinical evidence to suggest that these “disorders may be a clinical spectrum of one condition” and not distinct disease entities. He will also discuss diagnostic criteria and role of neuroimaging. Jim Rivello will review the available evidence, and emphasize the best clinical practices for management in these children. First, he will discuss the goals of treatment i.e. seizure control, behavior improvement, cognition monitoring, and sleep EEG improvement. Second, he will formulate a treatment and follow‐up plan with indications for various medical (anti epileptic agents, steroids, nightly benzodiazepenes etc.) and surgical (multiple subpial transactions) options. Each speaker will also formulate an important research question for the future that will improve our understanding of these conditions for devising better treatment methods. Live interaction with the diverse group of audience will also provide a forum to discuss where and how we should move forward with a collaborative effort for advancing our knowledge and treatment of these conditions.

Language heterogeneity and regression in the autism spectrum disorders—Overlaps with other childhood language regression syndromes

Some third of parents of children on the autism spectrum report that their toddler’s language regressed, usually insidiously, or stagnated during a prolonged plateau. Regression was associated with loss of sociability, interest in toys, and other behavioral skills, without motor regression. After months or longer, language usually returns, but variably severe autistic features persist. Nonverbal cognitive skills may or may not be affected. Some parents recall some antecedent nonspecific illness or stressor like the absence of a parent, a move, or the birth of a sibling. Occasionally, regression seems temporally related to an epileptic seizure, suggesting an overlap with acquired epileptic aphasia (Landau–Kleffner syndrome—LKS) in which language regression is associated with either clinical seizures or subclinical perisylvian temporo-parietal epileptiform EEG activity. LKS onset peaks at 4–6 years, autistic regression before age 2 years and is infrequently associated with seizures or an epileptiform EEG, except in the rare case of disintegrative disorder, a late global autistic regression which, like LKS, may be associated with electrical status epilepticus in slow wave sleep. Mute or dysfluent children with LKS, autism, or developmental language disorders are unable to decode or have difficulty decoding acoustically presented language (speech). They are at higher risk for epilepsy than fluent children with the typically aberrant language of verbal children with autism. The pathogenesis of language regression remains unknown because autistic toddlers are rarely studied at the time of language regression so that no empirically validated effective treatment has yet been devised.

Thalamic lesion and epilepsy with generalized seizures, ESES and spike-wave paroxysms—Report of three cases

We report three patients, who have thalamic lesion and secondary generalized epilepsy with generalized spike wave pattern. The first two patients have unilateral perinatal lesion, one with generalized tonic-clonic seizures on awakening the other with Landau-Kleffner-like syndrome. During the course of the disease both children developed electrical status epilepticus in slow wave sleep (ESES). The third patient has a dominantly unilateral thalamic tumor and epilepsy that mimics juvenile myoclonic epilepsy. All the patients have a lesion located in the inferior-medial-posterior part of the thalamus. The role of some thalamic and subthalamic nuclei in the generalized spike-wave electrical pattern patophysiology is discussed, with emphasis on the possible role of the inhibitory system from the zona incerta.

Landau–Kleffner syndrome, electrical status epilepticus in slow wave sleep, and language regression in children

The Landau-Kleffner syndrome (LKS) and electrical status epilepticus in slow wave sleep (ESES) are rare childhood-onset epileptic encephalopathies in which loss of language skills occurs in the context of an epileptiform EEG activated in sleep. Although in LKS the loss of function is limited to language, in ESES there is a wider spectrum of cognitive impairment. The two syndromes are distinct but have some overlap. The relationship between the epileptiform EEG abnormalities and the loss of cognitive function remains controversial, even in LKS which is the most widely accepted as an acquired epileptic aphasia. Language regression also occurs in younger children, frequently in the context of a more global autistic regression. Many of these children have epileptiform EEGs. The term autistic regression with epileptiform EEG has been proposed for these children. Whether these children are part of an extended LKS spectrum is very controversial, because there are differences in age of onset, clinical phenotype, and EEG findings. An understanding of the available data on clinical characteristics, EEG findings, pathology, prognosis, and treatment of these syndromes is essential for further progress in this area.

Electrical Status Epilepticus in Slow Wave Sleep: Prospective Case Study of a Cortical Hearing Impairment

The development of a central hearing impairment is described in a young girl with risk factors for hearing impairment that included mosaic Down syndrome, leukemia, and chemotherapy. This case is unusual in the prospective regularity with which hearing was assessed from birth. The diagnosis is electrical status epilepticus in slow wave sleep, a rare childhood disorder, which was associated with lack of responsiveness to auditory signals, regression of emerging speech and language and other cognitive skills, and abnormal electroencephalographic (EEG) activity in both hemispheres. Treatment of the disorder with anticonvulsant medications and steroids has ameliorated the condition by suppressing the abnormal EEG activity and allowing substantial improvements in cognitive and social skills, although communication skills are improving more slowly.

Autistic regression and disintegrative disorder: How important the role of epilepsy?

At least a third of autistic toddlers regress in language, sociability, play, and often cognition. Many fewer children undergo a similar, unexplained regression after language is fully developed (disintegrative disorder [DD]). Epilepsy or a paroxysmal electroencephalogram (EEG) with/without clinical seizures, including electrical status epilepticus in slow wave sleep (ESES), may be associated, in occasional children, with either selective loss of language (Landau-Kleffner syndrome [LKS]) or with pervasive autistic regression. Fluctuation in language and behavior deficits should raise the suspicion of epilepsy. Review of the literature and of the author's experience suggests that epilepsy probably plays a relatively minor, although non-negligible, pathogenetic role in autistic regression. Multidisciplinary, possibly multi-institutional, longitudinal studies that encompass the regression are needed to sharpen diagnostic criteria to devise more effective therapies.