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Neurology India 2022Prediction of outcome of West syndrome (WS) in relation to etiology and electrophysiology remain pertinent challenges.
BACKGROUND
Prediction of outcome of West syndrome (WS) in relation to etiology and electrophysiology remain pertinent challenges.
OBJECTIVE
This study aimed to compare electro-clinical and imaging characteristics between WS of "unknown-etiology"; "symptomatic"WS; to gauge the evolution and impact of electroencephalographic (EEG) patterns on seizure outcomes.
MATERIALS AND METHODS
Electro-clinico-radiological data of 76 children with WS who were followed up for atleast 1 year was collected for reviewing clinical, therapeutic and EEG profiles (sub-typed as typical and modified hypsarrhythmia [HA]). Quantified seizure scores were assessed.
RESULTS
Among 76 children included in this retrospective analysis, 31 (40.8%) were of unknown-etiology and 45 (59.2%) were "symptomatic" (structural cause/developmental-encephalopathy). Children with symptomatic WS (p = 0.037), specifically with gliosis on imaging (p = 0.05) and typical HA (including the multifocal subtype; P = 0.023) were more likely to have other seizure types before onset of spasms and exhibit prior delay or regression in milestones (p = 0.017). There was negative correlation between time to diagnosis and reduction in seizure scores (r = -0.32; p = 0.005).Significant reduction was noted in seizure scores with pharmacotherapy, irrespective of etiology (P < 0.001 in unknown-etiology and symptomatic subgroups). Seizure freedom rates did not differ between typical and modified HA groups (p = 0.215) with a higher proportion of children with meaningful reduction in seizure scores in the former sub-group (p = 0.030). Children who failed to achieve seizure remission were more likely to exhibit developmental impairment (p = 0.019).
CONCLUSIONS
Early diagnosis and initiation of optimal therapy is crucial towards improving outcome, irrespective of etiology (which impacts pre-spasm development) and HA subtypes.
Topics: Child; Electroencephalography; Humans; Infant; Referral and Consultation; Retrospective Studies; Spasms, Infantile; Treatment Outcome
PubMed: 35263882
DOI: 10.4103/0028-3886.336325 -
Frontiers in Pediatrics 2021To characterize the electro-clinical presentation of patients with pyridoxine-dependent epilepsy (PDE) and pyridoxal phosphate (PLP)-dependent epilepsy in order to...
To characterize the electro-clinical presentation of patients with pyridoxine-dependent epilepsy (PDE) and pyridoxal phosphate (PLP)-dependent epilepsy in order to determine whether some of them could be diagnosed as West syndrome, i. e., West syndrome that starts after the age of 2 months without other types of seizures (focal seizures for instance) before the onset of epileptic spasms. We analyzed data from an unpublished cohort of 28 genetically confirmed cases of PDE with antiquitine (ATQ) deficiency and performed a review of the literature looking for description of West syndrome in patients with either PDE with ATQ deficiency or PLP-dependent epilepsy with Pyridox(am)ine phosphate oxidase (PNPO) deficiency. Of the 28 cases from the ATQ deficiency French cohort, 5 had spasms. In four cases, spasms were associated with other types of seizures (myoclonus, focal seizures). In the last case, seizures started on the day of birth. None of these cases corresponded to West syndrome. The review of the literature found only one case of PNPO deficiency presenting as West syndrome and no case of ATQ deficiency. The presentation of PDE- and PLP-dependent epilepsy as West syndrome is so exceptional that it probably does not justify a systematic trial of pyridoxine or PLP. We propose considering a therapeutic trial with these vitamins in West syndrome if spasms are associated with other seizure types or start before the age of 2 months.
PubMed: 33748042
DOI: 10.3389/fped.2021.621200 -
RNA Biology Jul 2021Adenosine-to-inosine (A-to-I) editing is one of the most prevalent post-transcriptional RNA modifications in metazoan. This reaction is catalysed by enzymes called... (Review)
Review
Adenosine-to-inosine (A-to-I) editing is one of the most prevalent post-transcriptional RNA modifications in metazoan. This reaction is catalysed by enzymes called adenosine deaminases acting on RNA (ADARs). RNA editing is involved in the regulation of protein function and gene expression. The numerous A-to-I editing sites have been identified in both coding and non-coding RNA transcripts. These editing sites are also found in various genes expressed in the central nervous system (CNS) and play an important role in neurological development and brain function. Aberrant regulation of RNA editing has been associated with the pathogenesis of neurological and psychiatric disorders, suggesting the physiological significance of RNA editing in the CNS. In this review, we discuss the current knowledge of editing on neurological disease and development.
Topics: Adenosine; Amyotrophic Lateral Sclerosis; Astrocytoma; Bipolar Disorder; Central Nervous System Neoplasms; Epilepsy; Humans; Inosine; Kv1.1 Potassium Channel; MicroRNAs; RNA Editing; Receptor, Serotonin, 5-HT2C; Receptors, AMPA; Schizophrenia; Spasms, Infantile
PubMed: 33393416
DOI: 10.1080/15476286.2020.1867797 -
Journal of Family Medicine and Primary... Jan 2021This study was intended to document the clinical profile and treatment outcome of West syndrome in children attending a tertiary care centre in Northern India.
BACKGROUND
This study was intended to document the clinical profile and treatment outcome of West syndrome in children attending a tertiary care centre in Northern India.
METHODS
Data were collected by a retrospective chart review of children diagnosed with West syndrome between January 2017 to January 2018. Information was recorded pertaining to the age at onset and presentation, etiology, and associated co-morbidities; results of electroencephalography (EEG) and neuroimaging; treatment given; and final outcome. The following drugs were used for treatment: ACTH ( = 7), prednisolone ( = 17), vigabatrin ( = 25), sodium valproate ( = 28), clonazepam ( = 30), and levetiracetam ( = 13) and modified Atkins diet ( = 7). The response was categorized as spasm cessation, partial improvement (>50% improvement), or no improvement.
RESULTS
Records of 30 children (21 boys) were analyzed. The median (IQR) age at onset was 4 (3, 6.5) months. The median (IQR) lag time to treatment was 5 (2,14) months. Eight (26%) were premature, 2 (7%) were small for gestational age, birth asphyxia in 56%, neonatal encephalopathy in 62%. EEG findings were hypsarrhythmia in 13 (43.3%) children and modified hypsarrhythmia in 9 (30%) children. MRI finding was periventricular leukomalacia (54.1%), cystic encephalomalacia (13.8%), normal MRI (20.7%) and one had arrested hydrocephalus. There was no improvement with valproate (93%), clonazepam (89%), levetiracetam (78%). Cessation of spasm was achieved with vigabatrin (28%), prednisolone (38.2%), ACTH (42.8%). Hypsarrhythmia resolved with improvement in of background and other epileptiform abnormalities in 17 children.
CONCLUSION
The present research highlights favourable response of West syndrome to oral steroids, vigabatrin and ACTH with limited role of conventional antiepileptic drugs like sodium valporate, levetiracetam and clonazepam. Primary care physician plays a vital role in early recognition and treatment of epileptic spasm.
PubMed: 34017752
DOI: 10.4103/jfmpc.jfmpc_1405_20 -
Brain Sciences Oct 2020Potocki-Shaffer syndrome (PSS) is a rare non-recurrent contiguous gene deletion syndrome involving chromosome 11p11.2. Current literature implies a minimal region with... (Review)
Review
Potocki-Shaffer syndrome (PSS) is a rare non-recurrent contiguous gene deletion syndrome involving chromosome 11p11.2. Current literature implies a minimal region with haploinsufficiency of three genes, (parietal foramina), (multiple exostoses), and (craniofacial anomalies, and intellectual disability). The rest of the PSS phenotype is still not associated with a specific gene. We report a systematic review of the literature and included two novel cases. Because deletions are highly variable in size, we defined three groups of patients considering the PSS-genes involved. We found 23 full PSS cases (, and ), 14 cases with , and three with only. Among the latter, we describe a novel male child showing developmental delay, café-au-lait spots, liner postnatal overgrowth and West-like epileptic encephalopathy. We suggest PSS cases may have epileptic spasms early in life, and is likely to be the causative gene. Given their subtle presentation these may be overlooked and if left untreated could lead to a severe type or deterioration in the developmental plateau. If our hypothesis is correct, a timely therapy may ameliorate PSS phenotype and improve patients' outcomes. Our analysis also shows is a candidate for the overgrowth phenotype.
PubMed: 33126574
DOI: 10.3390/brainsci10110788 -
Indian Journal of Pediatrics Aug 2021
Topics: Adrenocorticotropic Hormone; Humans; Pharmaceutical Preparations; Spasms, Infantile
PubMed: 33772432
DOI: 10.1007/s12098-021-03747-z -
Cureus Nov 2022West syndrome (WS), also known as infantile spasms, is a severe form of epileptic disorder of infancy and early childhood. It was first described by William West in...
West syndrome (WS), also known as infantile spasms, is a severe form of epileptic disorder of infancy and early childhood. It was first described by William West in 1841. Children with WS exhibit a triad of myoclonic-tonic seizures (spasms), a distinct electroencephalogram (EEG) pattern known as hypsarrhythmia and psychomotor development arrest. WS is classified into three main categories as symptomatic, idiopathic and cryptogenic based on etiological factors. The long-term prognosis depends on the etiological cause, but generally has a poor prognosis, and is associated with impaired development, neurologic structural anomalies, autism spectrum disorder and death. Treatment guidelines from the American Academy of Neurology and Child Neurology Society recommend that adrenocorticotropic hormone (ACTH) and vigabatrin are possibly effective in the cessation of spasms and hypsarrhythmia. We report an incidental diagnosis of WS in a six-month-old male baby that went to the Pediatric Emergency Department due to upper respiratory tract symptoms. The diagnosis was made after the development of spasms during a medical examination. This case highlights the importance of early diagnosis, parental education and prompt effective treatment as it may improve prognosis.
PubMed: 36579257
DOI: 10.7759/cureus.31848 -
Molecular Genetics and Metabolism Nov 2023We provide a comprehensive overview of inherited metabolic disorders (IMDs) in which epilepsy is a prominent manifestation. Our unique database search has identified 256... (Review)
Review
We provide a comprehensive overview of inherited metabolic disorders (IMDs) in which epilepsy is a prominent manifestation. Our unique database search has identified 256 IMDs associated with various types of epilepsies, which we classified according to the classic pathophysiology-based classification of IMDs, and according to selected seizure-related factors (neonatal seizures, infantile spasms, myoclonic seizures, and characteristic EEG patterns) and treatability for the underlying metabolic defect. Our findings indicate that inherited metabolic epilepsies are more likely to present in the neonatal period, with infantile spasms or myoclonic seizures. Additionally, the ∼20% of treatable inherited metabolic epilepsies found by our search were mainly associated with the IMD groups of "cofactor and mineral metabolism" and "Intermediary nutrient metabolism." The information provided by this study, including a comprehensive list of IMDs with epilepsy stratified according to age of onset, and seizure type and characteristics, along with an overview of the key clinical features and proposed diagnostic and therapeutic approaches, may benefit any epileptologist and healthcare provider caring for individuals with metabolic conditions.
Topics: Infant, Newborn; Humans; Spasms, Infantile; Epilepsy; Seizures; Metabolic Diseases; Epilepsies, Myoclonic; Electroencephalography
PubMed: 37659319
DOI: 10.1016/j.ymgme.2023.107690 -
Epilepsy & Behavior : E&B May 2022Dravet syndrome (DS) is a developmental and epileptic encephalopathy with evolving disease course as individuals age. In recent years, the treatment landscape of DS has... (Review)
Review
Dravet syndrome (DS) is a developmental and epileptic encephalopathy with evolving disease course as individuals age. In recent years, the treatment landscape of DS has changed considerably, and a comprehensive systematic review of the contemporary literature is lacking. Here we synthesized published evidence on the occurrence of clinical impacts by age, the economic and humanistic (health-related quality-of-life [HRQoL]) burden, and health state utility. We provide an evidence-based, contemporary visualization of the clinical manifestations, highlighting that DS is not limited to seizures; non-seizure manifestations appear early in life and increase over time, contributing significantly to the economic and humanistic burden of disease. The primary drivers of HRQoL in DS include seizure severity, cognition, and motor and behavioral problems; in turn, these directly affect caregivers through the extent of assistance required and consequent impact on activities of daily living. Unsurprisingly, costs are driven by seizure-related events, hospitalizations, and in-home medical care visits. This systematic review highlights a paucity of longitudinal data; most studies meeting inclusion criteria were cross-sectional or had short follow-up. Nonetheless, available data illustrate the substantial impact on individuals, their families, and healthcare systems and establish the need for novel therapies to address the complex spectrum of DS manifestations.
Topics: Activities of Daily Living; Epilepsies, Myoclonic; Epileptic Syndromes; Humans; Seizures; Spasms, Infantile
PubMed: 35334258
DOI: 10.1016/j.yebeh.2022.108661 -
American Journal of Medical Genetics.... Mar 2023The increased use of next-generation sequencing has expanded our understanding of the involvement and prevalence of mosaicism in genetic disorders. We describe a total...
The increased use of next-generation sequencing has expanded our understanding of the involvement and prevalence of mosaicism in genetic disorders. We describe a total of eleven cases: nine in which mosaic variants detected by genome sequencing (GS) and/or targeted gene panels (TGPs) were considered to be causative for the proband's phenotype, and two of apparent parental mosaicism. Variants were identified in the following genes: PHACTR1, SCN8A, KCNT1, CDKL5, NEXMIF, CUX1, TSC2, GABRB2, and SMARCB1. In addition, we identified one large duplication including three genes, UBE3A, GABRB3, and MAGEL2, and one large deletion including deletion of ARFGAP1, EEF1A2, CHRNA4, and KCNQ2. All patients were enrolled in the NYCKidSeq study, a research program studying the communication of genomic information in clinical care, as well as the clinical utility and diagnostic yield of GS for children with suspected genetic disorders in diverse populations in New York City. We observed variability in the correlation between reported variant allele fraction and the severity of the patient's phenotype, although we were not able to determine the mosaicism percentage in clinically relevant tissue(s). Although our study was not sufficiently powered to assess differences in mosaicism detection between the two testing modalities, we saw a trend toward better detection by GS as compared with TGP testing. This case series supports the importance of mosaicism in childhood-onset genetic conditions and informs guidelines for laboratory and clinical interpretation of mosaic variants detected by GS.
Topics: Humans; Alleles; Spasms, Infantile; Phenotype; Mosaicism; High-Throughput Nucleotide Sequencing; Proteins; Peptide Elongation Factor 1; GTPase-Activating Proteins; Potassium Channels, Sodium-Activated; Nerve Tissue Proteins
PubMed: 36563179
DOI: 10.1002/ajmg.a.63062