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Indian Journal of Pediatrics Jan 2020
Topics: Humans; Spasms, Infantile; Topiramate
PubMed: 31811502
DOI: 10.1007/s12098-019-03135-8 -
Developmental Medicine and Child... Apr 2023To explore the phenotypic spectrum and refine the genotype-phenotype correlation of DYNC1H1-related epilepsy.
AIM
To explore the phenotypic spectrum and refine the genotype-phenotype correlation of DYNC1H1-related epilepsy.
METHOD
The clinical data of 15 patients with epilepsy in our cohort and 50 patients with epilepsy from 24 published studies with the DYNC1H1 variants were evaluated.
RESULTS
In our cohort, 13 variants were identified from 15 patients (seven males, eight females). Twelve variants were de novo and seven were new. Age at seizure onset ranged from 3 months to 4 years 5 months (median age 1 year). Common seizure types were epileptic spasms, focal seizures, tonic seizures, and myoclonic seizures. Mild-to-severe developmental delay was present in all patients. Six patients were diagnosed with West syndrome and one was diagnosed with epileptic encephalopathy with continuous spikes and waves during slow sleep (CSWS). Collectively, in our cohort and published studies, 17% had ophthalmic diseases, 31% of variants were located in the stalk domain, and 92% patients with epilepsy had a malformation of cortical development (MCD).
INTERPRETATION
The phenotypes of DYNC1H1-related epilepsy included multiple seizure types; the most common epileptic syndrome was West syndrome. CSWS is a new phenotype of DYNC1H1-related epilepsy. One-third of the variants in patients with epilepsy were located in the stalk domain. Most patients had a MCD and developmental delay.
WHAT THIS PAPER ADDS
Nearly 40% of patients with DYNC1H1 variants had epilepsy. Ninety-two percent of patients with DYNC1H1-related epilepsy had malformation of cortical development. More than 10% of patients with DYNC1H1-related epilepsy were diagnosed with West syndrome. Continuous spikes and waves during slow sleep could be a new phenotype of DYNC1H1 variants. One-third of the variants in patients with epilepsy were located in the stalk domain.
Topics: Male; Female; Humans; Spasms, Infantile; Mutation; Epilepsy; Seizures; Genetic Association Studies; Electroencephalography; Cytoplasmic Dyneins
PubMed: 36175372
DOI: 10.1111/dmcn.15414 -
Indian Journal of Pediatrics Aug 2022
Topics: Electroencephalography; Humans; Infant; Seizures; Spasms, Infantile
PubMed: 35594027
DOI: 10.1007/s12098-022-04240-x -
Revue Neurologique Sep 2022Developmental and epileptic encephalopathies are conditions where there is developmental impairment related to both the underlying etiology independent of epileptiform... (Review)
Review
Developmental and epileptic encephalopathies are conditions where there is developmental impairment related to both the underlying etiology independent of epileptiform activity and the epileptic encephalopathy. Usually they have multiple etiologies. Therefore, long-term outcome is related to both etiology-related factors and epilepsy-related factors-age at onset of epilepsy, type(s) of seizure(s), type of electroencephalographic abnormalities, duration of the epileptic disorder. This paper focuses on long-term outcome of six developmental and epileptic encephalopathies with onset from the neonatal period to childhood: early epileptic encephalopathy with suppression bursts, West syndrome, Dravet syndrome, Lennox-Gastaut syndrome, epilepsy with myoclonic atonic seizures and epileptic encephalopathy with continuous spike and waves during slow-wave sleep including Landau-Kleffner syndrome. For each syndrome, definition, main etiologies if multiple, and long-term outcome are discussed.
Topics: Child; Electroencephalography; Epilepsies, Myoclonic; Epilepsy; Humans; Infant, Newborn; Lennox Gastaut Syndrome; Seizures; Spasms, Infantile
PubMed: 35489823
DOI: 10.1016/j.neurol.2022.01.009 -
Epilepsy & Behavior : E&B Dec 2020Epileptic Spasms (ES) is a type of seizure usually occurring in the context of a severe childhood epileptic syndrome associated to significant Electroencephalogram (EEG)... (Review)
Review
Epileptic Spasms (ES) is a type of seizure usually occurring in the context of a severe childhood epileptic syndrome associated to significant Electroencephalogram (EEG) abnormalities. There are three scenarios in which ES may occur. The first one is represented by West Syndrome (WS): ES occur in a previously non encephalopathic infant in association with the development of a hypsarrhythmic EEG pattern. In most cases, standard treatment with Adrenocorticotropic Hormone (ACTH), steroids or vigabatrin leads to a reversal of the electroclinical picture. The second scenario is represented by Developmental and Epileptic Encephalopathies (DEEs): ES are documented, often along other seizures types, in an infant who often shows developmental delay since birth; the EEG pattern is pathological both in wakefulness and in sleep, without typical features of hypsarrhythmia; therapies (with the exception of few potentially treatable syndromes) are poorly effective. The last scenario is represented by ES in the context of Focal Epilepsies (FEs): ES, sometimes showing focal signs or closely related to focal seizures, are associated with focal brain lesions. Treatment with ACTH, steroids or vigabatrin may not be effective as well as antiepileptic drugs for focal epilepsies. In drug-resistant patients, surgery should be considered. Although there are some gaps in our current scientific knowledge concerning the peculiar electroclinical and physiopathological features of ES, we nowadays possess the necessary tools to correctly frame this unique seizure type into one of these scenarios and therefore properly manage the diagnostic and therapeutic workup.
Topics: Child; Electroencephalography; Epilepsy; Humans; Infant; Spasm; Spasms, Infantile; Vigabatrin
PubMed: 33248400
DOI: 10.1016/j.yebeh.2020.107531 -
BMC Pediatrics Sep 2021West syndrome is a convulsive disorder of infancy with unique seizures and a characteristic background electroencephalograph pattern. Adrenocorticotropic hormone (ACTH)... (Observational Study)
Observational Study
BACKGROUND
West syndrome is a convulsive disorder of infancy with unique seizures and a characteristic background electroencephalograph pattern. Adrenocorticotropic hormone (ACTH) is effective in spasm cessation, yet metabolic consequences of this therapeutic agent in childhood have not been published.
METHODS
In this observational study we explored the cardiometabolic outcomes of 117 children with West syndrome (78 ACTH-treated and 39 non-ACTH-treated) monitored at a single medical center from 1995 to 2019 (median follow-up 7.2 years). Outcomes included the prevalence of cardiometabolic derangements (obesity, hypertension, and dyslipidemia) during infancy (< 2 years), early childhood (2-6 years), and childhood/adolescence (6-18 years).
RESULTS
The rates of metabolic derangements during infancy in the West syndrome cohort were high compared to childhood/adolescence (obesity 27.3 % vs. 3.3 %, [p = 0.010], diastolic hypertension 48.8 % vs. 5.1 % [p < 0.001], hypertriglyceridemia 71 % vs. 40 % [p = 0.008], low high-density lipoprotein cholesterol [HDL-c] 54.2 % vs. 12.9 % [p = 0.001], and elevated triglycerides/HDL-c ratios 62.5 % vs. 12.9 % [p < 0.001]). The proportion of systolic and/or diastolic blood pressure levels categorized as hypertensive was 58.5 % during infancy, 48.1 % during early childhood, and 26.3 % during childhood/adolescence. ACTH-treated patients had higher weight and weight-to-length z-scores and higher triglyceride levels during infancy compared to non-ACTH-treated patients (p = 0.008, p = 0.001, and p = 0.037, respectively), and higher triglyceride levels during early childhood (p = 0.050), with no significant group differences during childhood/adolescence.
CONCLUSIONS
Children with West syndrome apparently have an increased prevalence of cardiometabolic derangements more pronounced in infants and in ACTH-treated patients. These findings highlight the need to monitor these children for cardiometabolic derangements, even though these cardiometabolic abnormalities are transitory and tend to decrease with time. The health implications of cardiometabolic derangements during critical windows of growth and development warrant further investigation.
Topics: Adolescent; Child; Child, Preschool; Humans; Hypertension; Infant; Metabolic Syndrome; Obesity; Overweight; Risk Factors; Spasms, Infantile
PubMed: 34537045
DOI: 10.1186/s12887-021-02871-1 -
Pediatric Neurology Jul 2023Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) has epilepsy as a cardinal feature. Here we report two new female patients and review six previously...
Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) has epilepsy as a cardinal feature. Here we report two new female patients and review six previously published patients, one male and five females, with features of CDD but who never developed epilepsy. In contrast with the classical and severe CDD phenotype, they presented with milder gross motor delays, autism spectrum disorder, and no visual cortical impairment. Prolonged video electroencephalography was normal in adult cases but showed interictal frontal-temporal bilateral spikes and sharp waves in sleep in the three-year-old girl. Causative CDKL5 variants included two likely gene damaging (nonsense and frameshift) and six missense variants, being de novo or maternally inherited from asymptomatic females with skewed X-chromosome inactivation (two missense variants). Our data indicate that a milder form of CDD without epilepsy can occur in some cases without clear correlation with specific variants in the CDKL5 gene.
Topics: Male; Female; Humans; Autism Spectrum Disorder; Epilepsy; Spasms, Infantile; Epileptic Syndromes; Protein Serine-Threonine Kinases
PubMed: 37201242
DOI: 10.1016/j.pediatrneurol.2023.04.015 -
Seminars in Neurology Apr 2020Infantile spasm (IS) is a distinct epilepsy syndrome characterized by epileptic spasms (the clinical seizure type) and hypsarrhythmia (the electrographic abnormality).... (Review)
Review
Infantile spasm (IS) is a distinct epilepsy syndrome characterized by epileptic spasms (the clinical seizure type) and hypsarrhythmia (the electrographic abnormality). IS is frequently accompanied by impaired neurodevelopment and is often associated with structural, genetic, or metabolic etiologies. Prompt treatment of this severe epileptic encephalopathy improves long-term outcomes but remains elusive in many situations. Despite common misconceptions, even patients with identified etiologies or preexisting developmental delay benefit from proven standard therapies, including adrenocorticotropic hormone (ACTH), oral corticosteroids, or vigabatrin. Treatment efficacy should be assessed with electroencephalography at 2 weeks, and an alternative therapy is indicated if epileptic spasms or hypsarrhythmia have not resolved. Collaboration with primary care providers is critical to mitigate the potentially serious adverse effects of standard treatments and also to provide developmental interventions. Although new approaches are on the horizon, addressing current challenges and opportunities now can dramatically improve patient outcomes.
Topics: Adrenocorticotropic Hormone; Anticonvulsants; Glucocorticoids; Humans; Infant; Practice Guidelines as Topic; Spasms, Infantile
PubMed: 32143232
DOI: 10.1055/s-0040-1705121 -
Pediatrics International : Official... Sep 2020Neonatal epilepsies - neonatal seizures caused by remote symptomatic etiologies - are infrequent compared with those caused by acute symptomatic etiologies. The... (Review)
Review
Neonatal epilepsies - neonatal seizures caused by remote symptomatic etiologies - are infrequent compared with those caused by acute symptomatic etiologies. The etiologies of neonatal epilepsies are classified into structural, genetic, and metabolic. Electroencephalography (EEG) and amplitude-integrated EEG (aEEG) are essential for the diagnosis and monitoring of neonatal epilepsies. Electroencephalography / aEEG findings may differ substantially among infants, even within infants with variants in a single gene. Unusual EEG/aEEG findings, such as downward seizure patterns on aEEG, can be found. Neonatal seizures are exclusively of focal onset. An International League Against Epilepsy task force proposed that the seizure type is typically determined by the predominant clinical feature and is classified into motor or non-motor presentations. Ictal EEG usually demonstrates a sudden, repetitive, evolving, and stereotyped activities with a minimum duration of 10 s. In epileptic spasms and myoclonic seizures, the cut-off point of 10 s cannot be applied. One must always be aware of electro-clinical dissociation in neonates suspected to have seizures. Amplitude-integrated EEG is also useful for the diagnosis and monitoring of neonatal epilepsies but aEEG cannot be recommended as the mainstay because of its relatively low sensitivity and specificity. At present, EEG findings are not pathognomonic, although some characteristic ictal or interictal EEG findings have been reported in several neonatal epilepsies. Deep learning will be expected to be introduced into EEG interpretation in near future. Objective EEG classification derived from deep learning may help to clarify EEG characteristics in some specific cases of neonatal epilepsy.
Topics: Electroencephalography; Epilepsy; Epilepsy, Benign Neonatal; Humans; Infant; Infant, Newborn; Seizures; Sensitivity and Specificity; Spasms, Infantile
PubMed: 32153072
DOI: 10.1111/ped.14227 -
Seizure Mar 2022Infantile spasms belong to the group of epileptic encephalopathies that typically occur in early infancy and are often associated with severe developmental delay. Little...
BACKGROUND
Infantile spasms belong to the group of epileptic encephalopathies that typically occur in early infancy and are often associated with severe developmental delay. Little is known about whether focal features are part of the syndrome and thus occur independently of etiology, or whether focal features always indicate a cerebral lesion.
METHODS
In our study we included all patients with infantile spasms documented by prolonged video-electroencephalogram (EEG) monitoring between 7/2003 and 11/2020 and analysed symptoms such as tonic posturing, clonic movements, deviation of the eyes and unilateral deviation of the mouth. These symptoms were classified as lateralizing or non-lateralizing and the correlation to the presence of a lesion was investigated.
RESULTS
Eighteen patients (9 w/9 m) were included in the study. Lateralizing tonic posturing was found in 66.6% of the patients. Deviation of the eyes to one side and unilateral deviation of the mouth were detected in 61.1% and 11.1% of patients, respectively. Taking into account all symptoms (tonic posturing, clonic movements, deviation of the eyes, unilateral deviation of the mouth), focal signs were observed in a total of 94.4%, with only half of the total patient population having a cerebral lesion.
CONCLUSION
In our study, lateralizing symptoms in infantile spasms occurred independently of the presence of a lesion. In contrast, focal symptoms in older children or adults usually correlate with the presence and localization of a lesion. A possible hypothesis could be that the brain is still maturing in infancy.
Topics: Adult; Brain; Child; Electroencephalography; Humans; Infant; Mouth; Spasms, Infantile
PubMed: 35183031
DOI: 10.1016/j.seizure.2022.02.008