Age-dependent Epileptic Encephalopathy Research Articles

Early transient dysautonomia predicts the risk of infantile epileptic spasm syndrome onset: A prospective cohort study.

Infantile epileptic spasm syndrome (IESS) is an age-dependent epileptic encephalopathy with a significant risk of developmental regression. This study investigates the association between heart rate variability (HRV) in infants at risk of IESS and the clinical onset of IESS. Sixty neonates at risk of IESS were prospectively followed from birth to 12 months with simultaneous electroencephalogram (EEG) and electrocardiogram recordings for 60 min at every 2-month interval. HRV metrics were calculated from 5 min time-epoch during sleep including frequency domain measures, Poincare analysis including cardiac vagal index (CVI) and cardiac sympathetic index (CSI), and detrended fluctuation analysis (DFA α1, DFA α2). To assess the effect of each HRV metric at the 2-month baseline on the time until the first occurrence of either hypsarrhythmia on EEG and/or clinical spasm, univariate cox-proportional hazard models were fitted for each HRV metric. Infantile epileptic spasm syndrome was diagnosed in 20/60 (33%) of the cohort in a 12-month follow-up and 3 (5%) were lost to follow-up. The median age of developing hypsarrhythmia was 25 (7-53) weeks and clinical spasms at 24 (8-40) weeks. Three (5%) patients had clinical spasms without hypsarrhythmia, and 5 (8%) patients had hypsarrhythmia before clinical spasms at the initial presentation. The infants with high CSI (hazard ratio 2.5, 95% CI 1.2-5.2, P = 0.01) and high DFA α1 (hazard ratio 16, 95% CI 1.1-240, P = 0.04) at 2 months were more likely to develop hypsarrhythmia by the first year of age. There was a trend toward decreasing CSI and DFA α1 and increasing CVI in the first 8 months of age. Our data suggest that relative sympathetic predominance at an early age of 2 months may be a potential predictor for developing IESS. Hence, early HRV patterns may provide valuable prognostic information in children at risk of IESS allowing early detection and optimization of cognitive outcomes. Whether early intervention to restore sympathovagal balance per se would provide clinical benefit must be addressed by future studies.

Retrospective Evaluation of Patients with Infantile Spasm Diagnosis

Introduction: Infantile spasm (West Syndrome) (IS) is an age-dependent epileptic encephalopathy clinic specific to the first two years of life. Infantile spasm is the most known epileptic syndrome of infancy with typical seizures in the form of spasm, psychomotor retardation and hypsarrhythmia on electroencephalography. Typical spasms are in the form of flexor/extensor contractions that last for about 2-5 seconds, which usually symmetrically involves all muscle groups in the body. Material and Method: In this study, the data of patients, who were followed up with the diagnosis of "infantile spasm" in the Pediatric Neurology Clinic of Mersin City Training and Research Hospital between 2020 and 2022, were retrospectively analyzed. Demographic characteristics, clinical, EEG and MRI findings of the patients were analyzed. Results: Eighteen patients were included in the study. Ten (55.5%) of our patients were male and 8 (44.5%) were female. The mean age of patients was ……. years. 11 (61.1%) patients were in the symptomatic group, 5 (27.7%) patients were in the cryptogenic group, and 2 (11.1%) patients were in the idiopathic group. At the time of diagnosis, there was flexor spasm, extensor spasm, mixt spasm, tonic seizure, myoclonic seizure in 5 (27,7%), 4 (22,2%), 4 (22,2%), 3 (16,6%), and 2 (11,1%) patients, respectively. Hypsarrhythmia, suppression-burst pattern, focal epileptic abnormality and generalized epileptic abnormality was observed in 8 (44,4%), 4 (22,2%), 3 (16,6%), and 3 (16,6%) patients, respectively. Of the 14 patients who were first diagnosed, 8 (57.1%) were treated with ACTH, 4 (28.6%) with phenobarbital, 2 (14.3%) with vigabatrin. Conclusion: Infantile spasm is an important age-related encephalopathy with severe neurological sequelae, resistant seizures, and high morbidity and mortality all over the world and in our country. Spasms cause further damage to the central nervous system, which continues to develop. For this reason, a positive contribution can be made in terms of prognosis with early and appropriate treatment.

Clinical spectrum and treatment outcome of 95 children with continuous spikes and waves during sleep (CSWS).

Continuous spikes and waves during sleep (CSWS) is an epileptic encephalopathy characterized by generalised epileptiform activity and neurocognitive dysfunction. Causes and outcome are diverse and treatment is mainly empirical. Retrospective descriptive analysis of clinical and EEG data of children with CSWS diagnosed between 1998 and 2018at the University Hospital Heidelberg. Ninety-five children were included with a median age at diagnosis of 5.4 years. A structural/metabolic aetiology was found in 43.2%, genetic alterations in 17.9%, while it remained unknown in 38.9%. The proportion of patients with genetic aetiology increased from 10.3% (1998-2007) to 22.8% (2008-2018). On average, each patient received 5 different treatments. CSWS was refractory in >70% of cases, steroids and neurosurgery were most effective. No difference was observed between children with CSWS or Near-CSWS (Spike-Wave-Index 40-85%). Our cohort confirms CSWS as an age-dependent epileptic encephalopathy. Structural brain abnormalities were most frequent, but genetic causes are increasingly identified. More specific criteria for the diagnosis and treatment goals should be elaborated and implemented based on evidence. This study is the largest monocentric observational study on treatment effects in children with CSWS, providing data for diagnostic and therapeutic decisions.

Diagnostic and therapeutic experience of child with neonatal epilepsy: from ICU to home (сlinical case)

Ohtahara syndrome is the earliest of age-dependent epileptic encephalopathies, characterized by an early onset at the age of 3 months (most often the first 10 days of life), ‘suppression-burst’ pattern on EEG both in wakefulness and in sleep, resistance to standard AED therapy, a high probability of poor prognosis in the form of severe psychomotor retardation and death in infancy.

Animal models of infantile spasms

Infantile spasms(IS), an age-dependent epileptic encephalopathy seen in infancy, is characterized by unique electro-clinical features and pharmacological reactions.Most conventional antiepileptic drugs are ineffective for IS.Hormonal treatment(including adrenocorticotropic hormone ACTH, and oral steroids)and vigabatrin(VGB)now widely used as first-line treatments for IS, have certain effects on IS, but the effect of these two options on long-term outcomes has not been established.The etiology of IS is variable.It is unclear that how a wide variety of conditions result a common phenotype.Ideal animal models can help to understand pathogenesis of disease and explore new therapies to improve the ultimate outcome.This review summarizes the research status of animal models of IS. Key words: Infantile spasm; Animal model; Pathogenesis; New drug therapy

Cryptogenic West syndrome: Clinical profile, response to treatment and prognostic factors

Abstract Introduction West syndrome (WS) is an age-dependent epileptic encephalopathy in which the prognosis varies according to the, not always identified, underlying origin. Objectives To define the profile of cryptogenic (a least studied isolated sub-group) WS, in Spain. To study its outcome, response to different treatments, and to establish prognostic factors. Patients and methods The study included a review of the medical records of 16 patients diagnosed with cryptogenic WS during the period, 2000–2015. The mean follow-up time was 6.6 years, with a minimum of 2 years. Results The large majority (11/16) were male. The mean age at onset was 6 months, and 6/16 had a family history of idiopathic epilepsy. The first line treatment with vigabatrin had an electrical–clinical response in 5/16 patients, with the remaining cases responding to adrenocorticotropic hormone (ACTH). Almost half (44%) of the patients progressed to other types of epilepsy, with no difference between those treated with vigabatrin or ACTH. A greater number of adverse effects were obtained with ACTH, with no retinal involvement being observed with vigabatrin. The aetiological cause was found in 2/16. Being female, late onset, and early control of the hypsarrhythmia, were factors of a good prognosis. Conclusions The overall prognosis of cryptogenic WS was more serious than expected. Although the incidence of Lennox–Gastaut syndrome was low, the progression to focal epilepsy was the most common, with it appearing within the first 2 years of the diagnosis. The initial response to vigabatrin was lower than expected, but the long-term result was comparable to ACTH.

EPILEPTIC ENCEPHALOPATHIES WITH ELECTRICAL STATUS EPILEPTICUS OF SLOW-WAVE SLEEP (ESES): DIAGNOSIS AND PHARMACOTHERAPY

Electrical status epilepticus of slow sleep (ESES) is a sleep EEG pattern with a continuous (85-100%) diffuse epileptiform activity. The morphology of these epileptiform complexes is identical to benign epileptiform discharges of childhood (BEDC). Epilepsy with ESES (or Penelope Syndrome) is a form of age-dependent epileptic encephalopathies with continuous spike-wave activity during slow wave sleep. This group of epilepsies also includes Pseudo-Lennox syndrome, Landau-Kleffner syndrome, autistic epileptiform regression and some others. Usually, the ESES pattern correlates with the severity of cognitive deficit in epileptic children. The list of anti-epileptic drugs (AEDs) used in pharmacotherapy of epileptic encephalopathies includes valproates, levetiracetam, ethosuximide, sulthiame, topiramate, zonisamide and benzodiazepines; those are given in monotherapy or rationalized combined therapy. Levetiracetam was highly effective in 67.6% of patients with ESES (n=23); among them, two cases of clinical and EEG remission during the pre-puberty period, nine cases of clinical remission and 12 cases with a significant decrease in seizures and epileptiform discharges. In 20.6% of patients (n=7), the pharmacotherapy showed low efficacy. In 11.8% of patients (n=4), aggravation of the disease was noted. Combinations of levetiracetam with valproates and levetiracetam with ethosuximide were found the most effective AEDs. In the cases of epileptogenic structural defect that underlines drug-resistant epilepsy with ESES, neurosurgical intervention is recommended.

Cryptogenic West syndrome: Clinical profile, response to treatment and prognostic factors

West syndrome (WS) is an age-dependent epileptic encephalopathy in which the prognosis varies according to the, not always identified, underlying origin. To define the profile of cryptogenic (a least studied isolated sub-group) WS, in Spain. To study its outcome, response to different treatments, and to establish prognostic factors. The study included a review of the medical records of 16 patients diagnosed with cryptogenic WS during the period, 2000-2015. The mean follow-up time was 6.6 years, with a minimum of 2 years. The large majority (11/16) were male. The mean age at onset was 6 months, and 6/16 had a family history of idiopathic epilepsy. The first line treatment with vigabatrin had an electrical-clinical response in 5/16 patients, with the remaining cases responding to adrenocorticotropic hormone (ACTH). Almost half (44%) of the patients progressed to other types of epilepsy, with no difference between those treated with vigabatrin or ACTH. A greater number of adverse effects were obtained with ACTH, with no retinal involvement being observed with vigabatrin. The aetiological cause was found in 2/16. Being female, late onset, and early control of the hypsarrhythmia, were factors of a good prognosis. The overall prognosis of cryptogenic WS was more serious than expected. Although the incidence of Lennox-Gastaut syndrome was low, the progression to focal epilepsy was the most common, with it appearing within the first 2 years of the diagnosis. The initial response to vigabatrin was lower than expected, but the long-term result was comparable to ACTH.

Altered Default Mode Network on Resting-State fMRI in Children with Infantile Spasms.

Infantile spasms (IS) syndrome is an age-dependent epileptic encephalopathy, which occurs in children characterized by spasms, impaired consciousness, and hypsarrhythmia. Abnormalities in default mode network (DMN) might contribute to the loss of consciousness during seizures and cognitive deficits in children with IS. The purpose of the present study was to investigate the changes in DMN with functional connectivity (FC) and amplitude of low-frequency fluctuation (ALFF), the two methods to discover the potential neuronal underpinnings of IS. The consistency of the two calculate methods of DMN abnormalities in IS patients was also our main focus. To avoid the disturbance of interictal epileptic discharge, our testing was performed within the interictal durations without epileptic discharges. Resting-state fMRI data were collected from 13 patients with IS and 35 sex- and age-matched healthy controls. FC analysis with seed in posterior cingulate cortex (PCC) was used to compare the differences between two groups. We chose PCC as the seed region because PCC is the only node in the DMN that directly interacts with virtually all other nodes according to previous studies. Furthermore, the ALFF values within the DMN were also calculated and compared between the two groups. The FC results showed that IS patients exhibited markedly reduced connectivity between posterior seed region and other areas within DMN. In addition, part of the brain areas within the DMN showing significant difference of FC had significantly lower ALFF signal in the patient group than that in the healthy controls. The observed disruption in DMN through the two methods showed that the coherence of brain signal fluctuation in DMN during rest was broken in IS children. Neuronal functional impairment or altered integration in DMN would be one neuroimaging characteristic, which might help us to understand the underlying neural mechanism of IS. Further studies are needed to determine whether the disturbed FC and ALFF observed in the DMN are related to cognitive performance in IS patients.

Lennox–Gastaut Syndrome: A State of the Art Review

Lennox-Gastaut syndrome (LGS) is a severe age-dependent epileptic encephalopathy usually with onset between 1 and 8 years of age. Functional neuroimaging studies recently introduced the concept of Lennox-Gastaut as "secondary network epilepsy" resulting from dysfunctions of a complex system involving both cortical and subcortical structures (default-mode network, corticoreticular connections, and thalamus). These dysfunctions are produced by different disorders including hypoxic-ischemic encephalopathies, meningoencephalitis, cortical malformations, neurocutaneous disorders, or tumors. The list of etiologies was expanded to pathogenic copy number variants at whole-genome array comparative genomic hybridization associated with late-onset cases or pathogenic mutations involving genes, such as GABRB3, ALG13, SCN8A, STXBP1, DNM1, FOXG1, or CHD2. Various clinical trials demonstrated the usefulness of different drugs (including rufinamide, clobazam, lamotrigine, topiramate, or felbamate), ketogenic diet, resective surgery, corpus callosotomy, and vagus nerve stimulation in the treatment of epileptic manifestations. The outcome of LGS often remains disappointing regarding seizure control or cognitive functioning. The realization of animal models, which are still lacking, and the full comprehension of molecular mechanisms involved in epileptogenesis and cognitive impairment would give a relevant support to further improvements in therapeutic strategies for LGS patients.

EFFICACY AND SAFETY OF LEVETIRACETAM IN CHILDREN WITH ELECTRICAL STATUS EPILEPTICUS DURING SLOW-WAVE SLEEP (ESES)

Electrical status epilepticus during slow-wave sleep (ESES) is an EEG pattern of continuous (85-100%) diffuse epileptiform activity in the sleep EEG. The morphology of the epileptiform complexes is identical to benign epileptiform discharges of childhood (BEDC). Epilepsy with ESES (or “Penelope Syndrome”) is a form of age-dependent epileptic encephalopathies with the phenomenon of continuous spike-waves during slow wave sleep. This group of epilepsies also includes Pseudo-Lennox syndrome, Landau-Kleffner syndrome, autistic epileptiform regression and some others. In most cases, the ESES pattern correlates with the severity of cognitive deficit in this population of epileptic children. The aim of this study was to evaluate the efficacy and safety of levetiracetam in children with the ESES pattern in the EEG. Materials and Methods. During the period of 2010-2016, 34 epileptic children with ESES patterns in the EEG (14 boys and 20 girls) treated with levetiracetam (33 in combined and 1 in monotherapy) were studied. Results. Twenty eight of the patients with ESES patterns in the sleep EEG were diagnosed with the ESES form of epilepsy. Among them, 7 idiopathic, 13 symptomatic, and 8 “symptomatic” cases of ESES (the latter resulted from “double pathology” of idiopathic + hypoxic-ischemic factors and these children had cerebral palsy). Among other ESES patients, 3 cases were of Pseudo-Lennox syndrome, 2 cases of Landau-Kleffner syndrome and one girl with autistic epileptiform regression. All 28 children received levetiracetam at therapeutic doses of 20-80 mg/kg/daily. Levetiracetam was highly effective in 67.6% of patients (n=23); of those, 2 children showed full clinical and electroencephalographic remission before reaching puberty, 9 children had clinical remission and 12 children had a significant decrease in seizures and epileptiform discharges. A low efficacy of levetiracetam was seen in 20.6% (n=7) of patients. Disease aggravation (seizures and epileptiform discharges) was found in 11.8% (n=4) of patients. Other negative effects were observed in only 4 (11.8%) children (3 cases of agitation and sleep disturbance and one case of allergic rash). In conclusion, levetiracetam is a highly effective medication (67.6% of cases) in combined antiepileptic therapy in children with ESES. However, the risk of exacerbation was as high as 11.8%. The most effective combinations of levetiracetam were those with valproates and ethosuximide.

Exome Sequencing Identifying Dual Mutations in Calcium Signaling Genes GNAO1 and ATP2B3 in a Patient with Early Infantile Epileptic Encephalopathy

Early infantile epileptic encephalopathy (EIEE) is an age-dependent epileptic encephalopathy. It occurs early in life with various types of seizures, especially tonic spasms and its overall prognosis is poor. We report a 5-year-old boy with EIEE, severe developmental delay, intractable epilepsy, and congenital cerebellar ataxia. His infantile spasms were treated successfully with ACTH, but he later developed intractable focal seizures. Whole exome sequencing revealed a maternally inherited missense mutation in the ATP2B3 gene (c.3338C > T/p.T1113M) and a de novo missense mutation in the GNAO1 gene (c.133G > C/p.G45R). Both genes are associated with calcium signaling pathways. The ATP2B3 gene is associated with intracellular calcium clearance, resulting in abnormal calcium homeostasis and X-linked spinocerebellar ataxia-1. The GNAO1 gene is associated with G protein signaling, affecting calcium signaling, and EIEE. Both mutations are related to maintain cellular calcium homeostasis, but the phenotype was not significantly more severe than those which have been reported.

LANDAU–KLEFFNER SYNDROME (ACQUIRED EPILEPTIC APHASIA) WITH A FOCUS ON ELECTROENCEPHALOGRAPHIC CRITERIA

Landau–Kleffner syndrome (LKS) is a disease from the group of age-dependent epileptic encephalopathies with the phenomenon of prolonged spike–wave activity in slow-wave sleep, which is manifested by acquired sensorimotor aphasia, impaired higher mental functions concurrent with various epileptic seizures and diffuse electroencephalographic (EEG) epileptiform changes in the absence of cerebral structural changes. In 1957, W. M. Landau, a pediatric neurologist, and F. R. Kleffner, a logopedist, first described the clinical presentation of the disease in 6 patients. The author associated the occurrence of aphasia with epileptiform EEG activity rather than with epileptic seizures, i. e. they per se formulated the modern concept of epileptic encephalopathy. There has been currently evidence that prolonged diffuse epileptiform activity has a damaging effect on a child’s developing brain, which is seen in impairments of speech and other higher mental functions. The age of patients with manifestations of LKS (3–5 years) is a critical period for the development of speech function. According to the concept of H. Doose (2003), congenital brain maturation disorder underlies LKS. The paper considers ideas on the origin of the LKS, including the possible genetic bases of diseases, epidemiological aspects, clinical and EEG manifestations with a detailed description ictal and interictal EEG changes, and treatment approaches, including the author’s data. The disease is characterized by an electroclinical triad: seizures (may be absent or may be single in a history), impaired higher mental functions (with a predominance of aphasic disorders), epileptiform EEG activity (a combination of regional and diffuse patterns with an increase during sleep).

Proteomic analysis on infantile spasm and prenatal stress

Infantile spasms (IS) are an age-dependent epileptic encephalopathy with severe cognitive dysfunction. Prenatal stress (PS) has been reported to increase the risk for IS through clinical and animal studies. We aim to investigate the mechanism of brain damage caused by IS and the effect of PS. Animals were divided into 4 groups: PS-spasm model, PS-saline control, NS-spasm model, and saline control. N-methyl-d-aspartate (NMDA) was used to induce spasm and swimming in cold water was used to induce PS. A proteomics-based approach was used to compare the NS-spasm model vs. saline control, and PS-spasm model vs. NS-spasm model. Gel image analysis was followed by mass spectrometric protein identification and bioinformatics analysis. We observed an increased spasm frequency (t=8.65, P<0.001), and a shorter latency period (t=3.96, P<0.001) in the PS-spasm model vs. the NS-spasm model. In the NS-spasm model vs. saline control, the main differentially expressed proteins were CFL1, PKM2, PRPS2, DLAT, CKB, DPYSL3, and SNAP25. In the PS-spasm model vs. NS-spasm model, MDH1 and YWHAZ were differentially expressed. YWHAZ was directly connected with CFL1 in protein networks. YWHAZ and CFL1 were further validated by Western blot analysis. The biological function of differentially expressed proteins indicates the pathogenesis of IS maybe relevant to energy metabolism, brain development, and neural remodeling. PS aggravated seizures in the NMDA-induced spasm model, YWHAZ, and CFL1 may be involved.

Dyskinesia as a new adverse effect of hormonal treatment in West syndrome

West syndrome is an age-dependent epileptic encephalopathy. Despite potential side effects, hormonal therapy remains the main treatment for West syndrome. Here, we report on 10 patients receiving steroid treatment who presented with unusual, mostly hyperkinetic, movements. Facial grimacing, repetitive mouth opening, adduction and abduction of upper and lower extremities, and periodical strabismus in different combinations were observed in all patients, independent of formulation, dose, duration, and efficacy of treatment. Symptoms disappeared in sleep and reappeared immediately on arousal. Dyskinesias stopped gradually after a month of discontinuation of treatment. Repeated EEGs did not show corresponding epileptiform activity. We conclude that these abnormal movements can be attributed to side effects of hormonal treatment.

Electroencephalogram of age-dependent epileptic encephalopathies in infancy and early childhood.

Epileptic encephalopathy syndromes are disorders in which the epileptiform abnormalities are thought to contribute to a progressive cerebral dysfunction. Characteristic electroencephalogram findings have an important diagnostic value in classification of epileptic encephalopathy syndromes. In this paper, we focus on electroencephalogram findings of childhood epileptic encephalopathy syndromes and provide sample illustrations.

14q12 duplication including FOXG1: Is there a common age-dependent epileptic phenotype?

Introduction: Duplications of 14q12 encompassing FOXG1 gene have been recently associated with developmental delay, severe speech impairment, epilepsy, aspecific neuroimaging findings and minor dysmorphisms. Aim and methods: In order to refine the epileptic phenotype associated with 14q12 duplications, we have performed a review of the electroclinical picture of the patients reported to date in the literature, adding a new personal case. A comprehensive set of clinical and instrumental data (with a particular focus on the electroclinical aspects including seizure type, age of onset, EEG at onset and after antiepileptic therapy, drug efficacy) has been taken into account. Results: 9/14 patients carrying 14q12 duplications developed seizures, all in the first months of life. Most of them developed infantile spasms (8/9 epileptic patients) and presented hypsarrhythmia or modified hypsarrhythmia on EEG. After therapy 5/9 patients became seizure free and 3/9 present a good seizure control. At last available follow up, 2/3 of the epileptic patients displayed an almost normal EEG, or a quite organized background activity, with diffuse or focal (mostly temporal) slowing. Conclusions: The review of the available data allowed to recognize a common epileptic core, characterized by early onset, age dependent epileptic encephalopathy with infantile spasms and typical, atypical or modified hypsarrhythmia. Antiepileptic therapy soon led to a good or complete control of seizures with a nearly normal background activity in most patients.

Epilepsy Surgery for Early Infantile Epileptic Encephalopathy (Ohtahara Syndrome)

Early infantile epileptic encephalopathy or Ohtahara syndrome is the earliest form of the age-dependent epileptic encephalopathies. Its manifestations include tonic spasms, focal motor seizures, suppression burst pattern, pharmaco-resistance, and dismal prognosis. The purpose of this study was to evaluate the effectiveness of epilepsy surgery in selected infants. We identified 11 patients, 9 from the literature and 2 from our institution that fulfilled diagnostic criteria of Ohtahara syndrome and had undergone epilepsy surgery in infancy. Seven of the 11 infants have remained seizure free (Engel class IA) and four are reportedly having rare to infrequent seizures (Engel class IIB). All patients experienced "catch up" development. In contrast to Ohtahara's15 pharmacotherapy managed patients, who had a mortality rate of approximately fifty percent, and those that survived continued to have seizures and were severely impaired, the outcome of selected surgically managed patients is much more favorable.

Cardiac autonomic dysfunction in West syndrome

West syndrome is an age-dependent epileptic encephalopathy. Autonomic changes are increasingly being recognized in patients with epilepsy: cardiac autonomic function is mediated by sympathetic and parasympathetic efferent activity to the heart and can provide information on the functional state of the autonomic nervous system. The goal of the study is to evaluate the effect of an early epileptic encephalopathy on the autonomic nervous system by measuring heart rate variability. Cardiac autonomic function was evaluated in 13 patients with West syndrome by measuring heart rate variability during 5 min epochs of ECG in wake, stage 2 and slow wave sleep. In 5 patients who developed subsequently another type of epilepsy, a second evaluation was performed after 3 years of follow-up. Results showed a lower heart rate in stage 2 sleep in patients with West syndrome. Spectral components did not show significant differences compared to age matched controls at the moment of presentation. After follow-up of 3 years we were able to demonstrate higher low frequency (LF), lower high frequency (HF) and a higher LF/HF ratio during slow wave sleep. This study shows a lower heart rate in patients presenting with West syndrome, already at the onset of the syndrome and before ACTH treatment. The epileptic encephalopathy is not sufficient to alter spectral components of heart rate at the moment of presentation. However, already after 3 years of epilepsy, chronic autonomic changes appear.

Molecular bases and clinical spectrum of early infantile epileptic encephalopathies

Epilepsy can be a challenging diagnosis to make in the neonatal and infantile periods. Seizures in this age group may be due to a serious underlying cause that results in an epileptic encephalopathy. Early infantile epileptic encephalopathy (EIEE) is a progressive neurologic condition that exhibits concomitant cognitive and motor impairment, and is often associated with severe intellectual disability. This condition belongs to the group of age-dependent epileptic encephalopathies, and thus the clinical and electro-encephalographic features change with age as the central nervous system evolves. The molecular bases and the clinical spectrum associated with the early infantile epileptic encephalopathies continue to expand as new genetic discoveries are made. This review will highlight the molecular etiologies of early infantile epileptic encephalopathy, and the clinical and electro-encephalographic changes that take place in these epileptic phenotypes as the brain develops.