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Indian Journal of Pediatrics Aug 2022To determine epilepsy and neurodevelopmental outcomes beyond 2 y of age and their putative prognostic factors in children with West syndrome (WS).
OBJECTIVE
To determine epilepsy and neurodevelopmental outcomes beyond 2 y of age and their putative prognostic factors in children with West syndrome (WS).
METHODS
This cross-sectional study was initiated after approval from Institutional Ethics Committee. A follow-up cohort of 114 children (aged ≥ 2 y) diagnosed and treated for WS at the authors' center were assessed in-person for epilepsy and neurodevelopmental outcomes using Vineland Social Maturity Scale - Malin's adaptation for Indian children. Subsequently, age at onset, lead-time-to-treatment, etiology, and response to any of the standard therapies were analyzed as possible predictors of these outcomes.
RESULTS
Of 114 children (mean age: 55 ± 32 mo, 91 boys), structural etiology was the predominant underlying etiology (79.8%) for WS. At 2 y of age, 64% had ongoing seizures. At the last follow-up, 76% had social quotient < 55, and 39% had cerebral palsy (spastic quadriparesis in 21%). An underlying structural etiology was associated with ongoing seizures [OR (95% CI) 3.5 (1.4-9); p = 0.008] at 2 y of age and poor developmental outcomes [OR (95% CI): 3.3 (1.3-8.9); p = 0.016]. Complete cessation of spasms with the standard therapy was significantly associated with better seizure control [OR (95% CI): 5.4 (2.3-13); p < 0.001] and neurodevelopmental outcome [OR (95% CI): 5.2 (1.8-14.9); p < 0.001].
CONCLUSION
The majority of children with WS have a poor neurodevelopmental outcome and epilepsy control on follow-up. The underlying etiology and response to initial standard therapy for epileptic spasms have a prognostic role in predicting the neurological outcome in these patients on follow-up.
Topics: Adult; Aged; Aged, 80 and over; Anticonvulsants; Child; Child, Preschool; Cross-Sectional Studies; Electroencephalography; Epilepsy; Humans; Infant; Male; Middle Aged; Retrospective Studies; Seizures; Spasm; Spasms, Infantile; Young Adult
PubMed: 34623615
DOI: 10.1007/s12098-021-03918-y -
BMC Pediatrics Jul 2012Infantile spasms (IS; West syndrome) is a severe form of encephalopathy that typically affects infants younger than 2 years old. Pediatricians, pediatric neurologists,... (Review)
Review
BACKGROUND
Infantile spasms (IS; West syndrome) is a severe form of encephalopathy that typically affects infants younger than 2 years old. Pediatricians, pediatric neurologists, and other pediatric health care providers are all potentially key early contacts for families who have an infant with IS. The objective of this article is to assist pediatric health care providers in the detection of the disease and in the counseling and guidance of families who have an infant with IS.
METHODS
Treatment guidelines, consensus reports, and original research studies are reviewed to provide an update regarding the diagnosis and treatment of infants with IS. Web sites were searched for educational and supportive resource content relevant to providers and families of patients with IS.
RESULTS
Early detection of IS and pediatrician referral to a pediatric neurologist for further evaluation and initiation of treatment may improve prognosis. Family education and the establishment of a multidisciplinary continuum of care are important components of care for the majority of patients with IS. The focus of the continuum of care varies across diagnosis, initiation of treatment, and short- and long-term needs. Several on-line educational and supportive resources for families and caregivers of patients with IS were identified.
CONCLUSIONS
Given the possibility of poor developmental outcomes in IS, including the emergence of other seizure disorders and cognitive and developmental problems, early recognition, referral, and treatment of IS are important for optimal patient outcomes. Dissemination of and access to educational and supportive resources for families and caregivers across the lifespan of the child with IS is an urgent need. Pediatric health care providers are well positioned to address these needs.
Topics: Adrenocorticotropic Hormone; Anticonvulsants; Continuity of Patient Care; Directive Counseling; Humans; Infant; Infant, Newborn; Parents; Patient Education as Topic; Pediatrics; Spasms, Infantile; Vigabatrin
PubMed: 22830456
DOI: 10.1186/1471-2431-12-108 -
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 -
Brain : a Journal of Neurology Dec 2023STXBP1-related disorders are among the most common genetic epilepsies and neurodevelopmental disorders. However, the longitudinal epilepsy course and developmental end...
STXBP1-related disorders are among the most common genetic epilepsies and neurodevelopmental disorders. However, the longitudinal epilepsy course and developmental end points, have not yet been described in detail, which is a critical prerequisite for clinical trial readiness. Here, we assessed 1281 cumulative patient-years of seizure and developmental histories in 162 individuals with STXBP1-related disorders and established a natural history framework. STXBP1-related disorders are characterized by a dynamic pattern of seizures in the first year of life and high variability in neurodevelopmental trajectories in early childhood. Epilepsy onset differed across seizure types, with 90% cumulative onset for infantile spasms by 6 months and focal-onset seizures by 27 months of life. Epilepsy histories diverged between variant subgroups in the first 2 years of life, when individuals with protein-truncating variants and deletions in STXBP1 (n = 39) were more likely to have infantile spasms between 5 and 6 months followed by seizure remission, while individuals with missense variants (n = 30) had an increased risk for focal seizures and ongoing seizures after the first year. Developmental outcomes were mapped using milestone acquisition data in addition to standardized assessments including the Gross Motor Function Measure-66 Item Set and the Grasping and Visual-Motor Integration subsets of the Peabody Developmental Motor Scales. Quantification of end points revealed high variability during the first 5 years of life, with emerging stratification between clinical subgroups. An earlier epilepsy onset was associated with lower developmental abilities, most prominently when assessing gross motor development and expressive communication. We found that individuals with neonatal seizures or early infantile seizures followed by seizure offset by 12 months of life had more predictable seizure trajectories in early to late childhood compared to individuals with more severe seizure presentations, including individuals with refractory epilepsy throughout the first year. Characterization of anti-seizure medication response revealed age-dependent response over time, with phenobarbital, levetiracetam, topiramate and adrenocorticotropic hormone effective in reducing seizures in the first year of life, while clobazam and the ketogenic diet were effective in long-term seizure management. Virtual clinical trials using seizure frequency as the primary outcome resulted in wide range of trial success probabilities across the age span, with the highest probability in early childhood between 1 year and 3.5 years. In summary, we delineated epilepsy and developmental trajectories in STXBP1-related disorders using standardized measures, providing a foundation to interpret future therapeutic strategies and inform rational trial design.
Topics: Infant, Newborn; Child; Child, Preschool; Humans; Infant; Anticonvulsants; Spasms, Infantile; Epilepsy; Topiramate; Seizures; Munc18 Proteins
PubMed: 38015929
DOI: 10.1093/brain/awad287 -
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 -
AJNR. American Journal of Neuroradiology Oct 2018Despite the development of neuroimaging, identification of focal cortical dysplasia remains challenging. The purpose of this study was to show the longitudinal changes...
BACKGROUND AND PURPOSE
Despite the development of neuroimaging, identification of focal cortical dysplasia remains challenging. The purpose of this study was to show the longitudinal changes of MR imaging and FDG-PET in patients with West syndrome and subtle focal cortical dysplasia.
MATERIALS AND METHODS
Among 52 consecutive patients with West syndrome, 4 were diagnosed with subtle focal cortical dysplasia on 3T MR imaging. MR imaging and PET findings were evaluated longitudinally at onset and at 12 and 24 months of age.
RESULTS
At the onset of West syndrome, MR imaging demonstrated focal signal abnormalities of the subcortical white matter in 2 patients. In the other 2 patients, focal subcortical high-intensity signals became visible on follow-up T2WI as myelination progressed. PET at onset showed focal cortical hypometabolism in 3 patients, with 1 of these patients also having focal hypermetabolism and 1 having normal findings. On PET at 24 months, hypometabolism persisted in 2 patients and disappeared in 1, and hypermetabolism disappeared in 1. In 1 patient with normal MR imaging and PET findings at onset, focal hyperintensity and hypometabolism first appeared at 24 months of age. The findings on MR imaging and PET in these patients evolved differently with brain maturation and the clinical course.
CONCLUSIONS
Subtle focal cortical dysplasia can be undetectable on MR imaging at the onset of West syndrome and is not always accompanied by hypometabolism or hypermetabolism on PET. Longitudinal MR imaging and PET studies may be useful for detecting such lesions. Even in West syndrome with a congenital structural abnormality, PET findings evolve differently with brain maturation and the clinical condition.
Topics: Female; Humans; Infant; Infant, Newborn; Magnetic Resonance Imaging; Male; Malformations of Cortical Development; Neuroimaging; Positron-Emission Tomography; Spasms, Infantile; White Matter
PubMed: 30213810
DOI: 10.3174/ajnr.A5772 -
Boletin Medico Del Hospital Infantil de... 2023CDKL5 deficiency syndrome is caused by pathogenic variants in the CDKL5 gene, with a variable clinical spectrum ranging from patients with characteristics of autism...
BACKGROUND
CDKL5 deficiency syndrome is caused by pathogenic variants in the CDKL5 gene, with a variable clinical spectrum ranging from patients with characteristics of autism spectrum disorder to early-onset epilepsy refractory to treatment. Initially, until the gene was discovered, it was considered an atypical form of Rett syndrome. This study aimed to describe the clinical and molecular heterogeneity in CDLK5 disorders among three female patients with CDKL5 pathogenic variants.
CASE REPORTS
We reported three unrelated Mexican female patients evaluated for global developmental delay and epilepsy. All three cases were hemizygotes to a CDKL5 pathogenic variant. In one patient, we performed a 306 gene panel associated with epilepsy. In the other two cases, a human genomic microarray was performed. We describe their clinical features electroencephalogram and brain magnetic resonance evaluations.
CONCLUSIONS
CDKL5 deficiency syndrome represents a challenge for clinicians since the clinical manifestations, electroencephalographic and neuroimaging studies can be non-specific. This syndrome should be suspected in the presence of global developmental delay, autistic behavioral phenotype and epilepsy, associated or not with dysmorphia. Given the similarity between various epileptic encephalopathies, multigene panels including sequencing and duplication/deletion analysis should be requested in which this gene and its possible differential diagnoses are considered, without forgetting the usefulness of genomic techniques in unclear cases.
Topics: Humans; Female; Autism Spectrum Disorder; Spasms, Infantile; Epilepsy; Rett Syndrome
PubMed: 37490689
DOI: 10.24875/BMHIM.22000100 -
Epilepsia 2006Cognitive and behavioral impairments in West syndrome are analyzed at the onset of the disease. Multimodal sensory impairments, namely of the visual function, that are... (Review)
Review
Cognitive and behavioral impairments in West syndrome are analyzed at the onset of the disease. Multimodal sensory impairments, namely of the visual function, that are usually associated with the acute stage of the disease, are stressed as possible mechanisms interfering with cognitive development. This notion could open a rehabilitation prospective for functional disorders. Long-term developmental outcome is dependent on various factors, ranging from the primary lesions to the epilepsy evolution and use of drugs, up to environmental factors such as the quality of the family or that of the community within which the infant grows up.
Topics: Age Factors; Cognition Disorders; Comorbidity; Follow-Up Studies; Humans; Incidence; Infant; Intellectual Disability; Mental Disorders; Prognosis; Spasms, Infantile
PubMed: 17105461
DOI: 10.1111/j.1528-1167.2006.00689.x -
Epilepsia Nov 2013Epileptic encephalopathies (EEs) represent a group of severe epileptic disorders associated with cognitive and behavioral disturbances. The mechanisms of cognitive... (Review)
Review
Epileptic encephalopathies (EEs) represent a group of severe epileptic disorders associated with cognitive and behavioral disturbances. The mechanisms of cognitive disability in EEs remain unclear. This review summarized neuroimaging studies that have tried to describe specific fingerprints of brain activation in EE. Although the epileptic activity can be generated individually in different brain regions, it seems likely that the activity propagates in a syndrome-specific way. In some EEs, the epileptiform discharges were associated with an interruption of activity in the default mode network. In another EE, other mechanisms seem to underlie cognitive disability associated with epileptic activity, for example, abnormal connectivity pattern or interfering activity in the thalamocortical network. Further neuroimaging studies are needed to investigate the short-term and long-term impact of epileptic activity on cognition and development.
Topics: Brain Diseases; Cognition Disorders; Electroencephalography; Epilepsies, Myoclonic; Epilepsy; Humans; Infant; Intellectual Disability; Lennox Gastaut Syndrome; Neuroimaging; Polysomnography; Sleep; Spasms, Infantile
PubMed: 24571114
DOI: 10.1111/epi.12420 -
Seizure Oct 2013This study was intended to document the clinical profile and treatment outcome of West syndrome in children attending a tertiary care center in Northern India.
PURPOSE
This study was intended to document the clinical profile and treatment outcome of West syndrome in children attending a tertiary care center in Northern India.
METHOD
Data were collected by a retrospective chart review of children diagnosed with West syndrome between January 2008 and January 2012. 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: pyridoxine, prednisolone, vigabatrin, sodium valproate, nitrazepam, topiramate, and levetiracetam. The response was categorized as spasm cessation, partial improvement (>50% improvement), or no improvement. The final outcome was considered favorable when there was a complete cessation of spasms; with absence of relapse and no progression to other seizure types for at least 6 months.
RESULTS
Records of 148 children (120 boys) were analyzed. The mean (SD) age at onset and presentation was 5.3 (4.6) months, and 13.1 (7.3) months, respectively. Perinatal asphyxia (61.4%), neonatal sepsis/meningitis (10.6%), and postnatal meningitis (11.4%) were the predominant causes. The etiology could not be ascertained in 16.6% of children. Favorable outcome was observed in 45 (30.4%) children with spasm cessation rate of 25.4% with prednisolone. Age at onset, gender, time lag to treatment, presence of perinatal asphyxia, or co-morbid cerebral palsy did not affect the final outcome.
CONCLUSION
This study highlights the developing country perspective of children with West syndrome, including delayed presentation, adverse perinatal events as the predominant etiology, and modest response to oral steroids.
Topics: Anticonvulsants; Brain; Child, Preschool; Electroencephalography; Female; Humans; India; Infant; Male; Retrospective Studies; Spasms, Infantile; Treatment Outcome
PubMed: 23643625
DOI: 10.1016/j.seizure.2013.04.014