scholarly journals Profile of neonatal epilepsies

Neurology ◽  
2017 ◽  
Vol 89 (9) ◽  
pp. 893-899 ◽  
Author(s):  
Renée A. Shellhaas ◽  
Courtney J. Wusthoff ◽  
Tammy N. Tsuchida ◽  
Hannah C. Glass ◽  
Catherine J. Chu ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Diagnostic Testing ◽  
Epileptic Encephalopathy ◽  
Neonatal Seizure ◽  
Neonatal Seizures ◽  
Epileptic Encephalopathies ◽  
Brain Malformations ◽  
Symptomatic Seizures ◽  
Acute Symptomatic Seizures ◽  
Structural Brain

Objective:Although individual neonatal epilepsy syndromes are rare, as a group they represent a sizable subgroup of neonatal seizure etiologies. We evaluated the profile of neonatal epilepsies in a prospective cohort of newborns with seizures.Methods:Consecutive newborns with seizures were enrolled in the Neonatal Seizure Registry (an association of 7 US children's hospitals). Treatment and diagnostic testing were at the clinicians' discretion. Neonates with seizures related to epileptic encephalopathies (without structural brain abnormalities), brain malformations, or benign familial epilepsies were included in this analysis.Results:Among 611 consecutive newborns with seizures, 79 (13%) had epilepsy (35 epileptic encephalopathy, 32 congenital brain malformations, 11 benign familial neonatal epilepsy [BFNE], 1 benign neonatal seizures). Twenty-nine (83%) with epileptic encephalopathy had genetic testing and 24/29 (83%) had a genetic etiology. Pathogenic or likely pathogenic KCNQ2 variants (n = 10) were the most commonly identified etiology of epileptic encephalopathy. Among 23 neonates with brain malformations who had genetic testing, 7 had putative genetic etiologies. Six infants with BFNE had genetic testing; 3 had pathogenic KCNQ2 variants and 1 had a pathogenic KCNQ3 variant. Comorbid illnesses that predisposed to acute symptomatic seizures occurred in 3/35 neonates with epileptic encephalopathy vs 10/32 with brain malformations (p = 0.03). Death or discharge to hospice were more common among newborns with brain malformations (11/32) than those with epileptic encephalopathy (3/35, p = 0.01).Conclusions:Neonatal epilepsy is often due to identifiable genetic causes. Genetic testing is now warranted for newborns with epilepsy in order to guide management and inform discussions of prognosis.

scholarly journals Genomic Investigation of Infantile and Childhood Epileptic Encephalopathies in Kazakhstan: An Urgent Priority

2021 ◽  
Vol 12 ◽  
Author(s):  
Altynshash Jaxybayeva ◽  
Alissa Nauryzbayeva ◽  
Assem Khamzina ◽  
Meruert Takhanova ◽  
Assel Abilhadirova ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Intellectual Development ◽  
Structural Changes ◽  
Communication Disorders ◽  
Epileptic Encephalopathy ◽  
Epileptic Encephalopathies ◽  
Pathogenic Variants ◽  
Genetic Epilepsies ◽  
First Year Of Life ◽  
Genetically Determined

Objectives: Infantile and childhood epileptic encephalopathies are a group of severe epilepsies that begin within the first year of life and often portend increased morbidity. Many of them are genetically determined. The medical strategy for their management depends on the genetic cause. There are no facilities for genetic testing of children in Kazakhstan but we have a collection of data with already defined genes responsible for clinical presentations.Methods: We analyzed children with epileptic encephalopathies that began in the first 3 years of life and were accompanied by a delay/arrest of intellectual development, in the absence of structural changes in the brain. Such patients were recommended to undergo genetic testing using epileptic genetic panels in laboratories in different countries.Results: We observed 350 infants with clinical presentation of epileptic encephalopathies. 4.3% of them followed our recommendations and underwent genetic testing privately. In total 12/15 children became eligible for targeted treatment, 3/15 were likely to have non-epileptic stereotypies/movements, 2/15 were unlikely to respond to any therapy and all had a high chance of intellectual disability, behavioral and social communication disorders.Conclusion: The genetic results of 15/350 (4.3% of patients) have demonstrated the potential and enormous impact from gene panel analysis in management of epileptic encephalopathy. Availability of genetic testing within the country will improve management of children with genetic epilepsies and help to create a local database of pathogenic variants.

scholarly journals Genetic Testing of Epileptic Encephalopathies of Infancy: An Approach

2013 ◽  
Vol 40 (1) ◽  
pp. 10-16 ◽  
Author(s):  
Suvasini Sharma ◽  
Asuri N. Prasad
Keyword(s):  
Genetic Testing ◽  
Homeobox Gene ◽  
Causative Mutation ◽  
Cortical Function ◽  
Inborn Errors ◽  
Epileptic Encephalopathies ◽  
Intractable Seizures ◽  
Brain Malformations ◽  
Clinical Syndromes ◽  
Brain Insults

Abstract:The epileptic encephalopathies of infancy are a group of disorders characterized by intractable seizures, persistent abnormality of cortical function documented on EEG, and consequently impaired neuro-developmental outcomes. The etiologies vary and include; structural brain malformations, acquired brain insults, and inborn errors of metabolism in the majority of the affected patients. In a proportion of these cases no obvious etiology is identifiable on investigation. Recent advances in molecular diagnostics have led to the discovery of a number of gene defects that may be causal in many epileptic encephalopathies. Identification of the causative mutation is important for prognostic and genetic counseling, and may also carry treatment implications. The recently described genes include; Cyclin-Dependent Kinase-Like 5 gene (CDKL5), Protocadherin 19 (PCDH19), Sodium channel neuronal type 1a subunit gene (SCN1A), Aristaless-Related Homeobox Gene (ARX), and Syntaxin binding protein 1 gene (STXBP1), amongst others. Distinct electro-clinical syndromes are increasingly being identified amongst patients carrying the various mutations. In this review, we outline the approach to clinical evaluation and genetic testing of epileptic encephalopathies in infancy.

scholarly journals Developmental and epileptic encephalopathies: what we do and do not know

Brain ◽  
2020 ◽  
Author(s):  
Nicola Specchio ◽  
Paolo Curatolo
Keyword(s):  
Intellectual Disability ◽  
Genetic Testing ◽  
Developmental Delay ◽  
Causal Relationship ◽  
Autistic Spectrum Disorder ◽  
Epileptic Encephalopathy ◽  
Spectrum Disorder ◽  
Gene Variants ◽  
Clinical Tests ◽  
Epileptic Encephalopathies

Abstract Developmental encephalopathies, including intellectual disability and autistic spectrum disorder, are frequently associated with infant epilepsy. Epileptic encephalopathy is used to describe an assumed causal relationship between epilepsy and developmental delay. Developmental encephalopathies pathogenesis more independent from epilepsy is supported by the identification of several gene variants associated with both developmental encephalopathies and epilepsy, the possibility for gene-associated developmental encephalopathies without epilepsy, and the continued development of developmental encephalopathies even when seizures are controlled. Hence, ‘developmental and epileptic encephalopathy’ may be a more appropriate term than epileptic encephalopathy. This update considers the best studied ‘developmental and epileptic encephalopathy’ gene variants for illustrative support for ‘developmental and epileptic encephalopathy’ over epileptic encephalopathy. Moreover, the interaction between epilepsy and developmental encephalopathies is considered with respect to influence on treatment decisions. Continued research in genetic testing will increase access to clinical tests, earlier diagnosis, better application of current treatments, and potentially provide new molecular-investigated treatments.

scholarly journals Etiology of the Neonatal Seizures: An Epidemiological Study

2019 ◽  
Vol 6 (4) ◽  
pp. 129-132
Author(s):  
Ali Zafari ◽  
Fatemeh Pajouhandeh ◽  
Mehran Arab Ahmadi
Keyword(s):  
Neonatal Intensive Care ◽  
Final Diagnosis ◽  
The Body ◽  
Neonatal Seizure ◽  
First Episode ◽  
Epilepsy Syndrome ◽  
Acute Symptomatic Seizure ◽  
Symptomatic Seizures ◽  
Pediatric Neurologist ◽  
Acute Symptomatic Seizures

Background: Neonatal seizure is a rare neurologic condition. The current study aimed at determining the etiology of neonatal seizure. Methods: The current study evaluated the data of 100 neonates who were hospitalized at neonatal intensive care unit (NICU) during 2015-2017. A pediatric neurologist made the final diagnosis of seizure. Patients’ medical records were used to review neonatal seizure variables. SPSS (version 16) was used to perform the statistical analyses. Results: The current study enrolled 100 newborns (41% female) admitted to the NICU following the first episode of seizure and the body temperature of 36.8-39.2°C (mean: 37.2°C). Of 100 participants, 94 (94%) had acute symptomatic seizure and 6 (6%) were compatible with neonatal epilepsy syndrome criteria. According to the results, the commonest etiologies were the neonatal encephalopathy and hypoxic-ischemic encephalopathy constituting 82% of participants. Conclusion: The consequences of acute symptomatic seizures in neonates are determined mainly by the etiology of the seizures. Seizure burden and use of anti-seizure drugs may also have some impact, but this has yet to be fully defined.

scholarly journals Genetic Neonatal-Onset Epilepsies and Developmental/Epileptic Encephalopathies with Movement Disorders: A Systematic Review

2021 ◽  
Vol 22 (8) ◽  
pp. 4202
Author(s):  
Carlotta Spagnoli ◽  
Carlo Fusco ◽  
Antonio Percesepe ◽  
Vincenzo Leuzzi ◽  
Francesco Pisani
Keyword(s):  
Movement Disorders ◽  
Time Course ◽  
Neonatal Period ◽  
Age Of Onset ◽  
Brain Mri ◽  
Neonatal Seizure ◽  
Mri Findings ◽  
Epileptic Encephalopathies ◽  
Pathogenic Variants ◽  
Neonatal Onset

Despite expanding next generation sequencing technologies and increasing clinical interest into complex neurologic phenotypes associating epilepsies and developmental/epileptic encephalopathies (DE/EE) with movement disorders (MD), these monogenic conditions have been less extensively investigated in the neonatal period compared to infancy. We reviewed the medical literature in the study period 2000–2020 to report on monogenic conditions characterized by neonatal onset epilepsy and/or DE/EE and development of an MD, and described their electroclinical, genetic and neuroimaging spectra. In accordance with a PRISMA statement, we created a data collection sheet and a protocol specifying inclusion and exclusion criteria. A total of 28 different genes (from 49 papers) leading to neonatal-onset DE/EE with multiple seizure types, mainly featuring tonic and myoclonic, but also focal motor seizures and a hyperkinetic MD in 89% of conditions, with neonatal onset in 22%, were identified. Neonatal seizure semiology, or MD age of onset, were not always available. The rate of hypokinetic MD was low, and was described from the neonatal period only, with WW domain containing oxidoreductase (WWOX) pathogenic variants. The outcome is characterized by high rates of associated neurodevelopmental disorders and microcephaly. Brain MRI findings are either normal or nonspecific in most conditions, but serial imaging can be necessary in order to detect progressive abnormalities. We found high genetic heterogeneity and low numbers of described patients. Neurological phenotypes are complex, reflecting the involvement of genes necessary for early brain development. Future studies should focus on accurate neonatal epileptic phenotyping, and detailed description of semiology and time-course, of the associated MD, especially for the rarest conditions.

Provider Practices of Phenobarbital Discontinuation in Neonatal Seizures

2017 ◽  
Vol 33 (2) ◽  
pp. 153-157 ◽  
Author(s):  
Niranjana Natarajan ◽  
Christopher W. Beatty ◽  
Juliane Gust ◽  
Lorie Hamiwka
Keyword(s):  
Seizure Control ◽  
Prolonged Treatment ◽  
Published Data ◽  
Neonatal Seizures ◽  
Early Discontinuation ◽  
Treatment Length ◽  
Provider Practices ◽  
Factors Influencing ◽  
Symptomatic Seizures ◽  
Infectious Etiology

Neonatal seizures are treated with phenobarbital and prolonged treatment does not prevent postneonatal epilepsy. The authors documented factors influencing phenobarbital use and determined whether published data changed practice. A total of 83 neonates with symptomatic seizures, clinical or electrographic, were evaluated for treatment, incidence of postneonatal epilepsy, and associated factors. Median phenobarbital treatment was 81 days. Nineteen children (23%) developed postneonatal epilepsy. Longer duration of seizures and an infectious etiology were associated with postneonatal epilepsy suggesting no impact on duration of phenobarbital treatment. Treatment duration was associated with duration of seizures and use of a second antiseizure medication. This study supports early discontinuation of phenobarbital and suggests providers utilize factors such as use of a second antiseizure medication and time to seizure control to determine phenobarbital duration, despite prior studies suggesting no impact of treatment length.

Acute Symptomatic Seizures

2012 ◽  
Vol 18 (3) ◽  
pp. 109-119 ◽  
Author(s):  
Pedro Beleza
Keyword(s):  
Symptomatic Seizures ◽  
Acute Symptomatic Seizures

Abstract 16136: Underutilization of Appropriate Testing for Transthyretin Amyloidosis Despite Suspicious Clinical & Echocardiographic Findings

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Katelyn Young ◽  
Kinjal Banerjee ◽  
Maulin Patel ◽  
Sangeeta Prabhakar Bhat ◽  
Colin Reynolds ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Cardiac Amyloidosis ◽  
Chart Review ◽  
Diagnostic Testing ◽  
Wild Type ◽  
Transthyretin Amyloidosis ◽  
Highly Sensitive ◽  
Amyloid Light Chain ◽  
Positive Results ◽  
Echocardiographic Findings

Introduction: Both hereditary (hATTR) and wild-type (wtATTR) transthyretin amyloidosis are under-recognized causes of cardiomyopathy (CM) and heart failure. Certain findings on Transthoracic Echocardiography (TTE) and cardiac Magnetic Resonance Imaging (cMRI) are suggestive but not diagnostic of ATTR. Although biopsy historically has been the gold standard for diagnosis, patients can be diagnosed with the highly sensitive and specific technetium-99m pyrophosphate scan (Tc-99m PYP). Genetic testing is recommended to confirm hATTR in patients diagnosed with ATTR cardiac amyloidosis. Despite growing awareness of this condition, many cases remain undiagnosed. This study evaluated if patients with TTEs concerning for infiltrative CM received appropriate diagnostic testing for ATTR-CM. Methods: Our echocardiography registry was queried from January 2011 to March 2020 for patients with our echo lab’s embedded infiltrative CM code. Data on demographics, comorbidities, TTE variables, cMRI results, PYP scans, genetic testing and biopsy results were retrieved from electronic medical records. Thorough manual chart review excluded other causes of CM. Data was expressed as mean ± SD and n (%). Results: We retrieved 510 patients (mean age 64 ± 16 years; 43% female) with TTEs suspicious for infiltrative CM revealing a mean interventricular septal diameter (IVSd) of 1.6 ± 0.3 cm. Only 67 (13%) patients underwent cMRI with 11 (16%) suggestive of cardiac amyloidosis. Of the patients with suspicious TTEs, 16 (3.1%) had PYP scans and 24 (4.7%) had tissue biopsy, with positive results in 7 (44%) and 11 (46%), respectively. Genetic testing in 31 (6%) patients revealed known hATTR mutations in 2 (6.5%) patients. Cardiac amyloidosis was diagnosed in 23 (4.5%) with 11 ATTR (2 hATTR), 5 amyloid light chain, and 7 unknown subtype. Conclusion: Despite clinical and TTE findings suspicious for ATTR-CM, many patients did not undergo appropriate confirmatory testing (see Figure 1).

Trends in prescribing patterns of antiepileptic drugs among older adult inpatients in a Brazilian tertiary center

2021 ◽  
Vol 79 (1) ◽  
pp. 22-29
Author(s):  
Telma ASSIS ◽  
Aroldo BACELLAR ◽  
Luan CÔRTES ◽  
Silas SANTANA ◽  
Gersonita COSTA ◽  
...  
Keyword(s):  
Risk Factors ◽  
Antiepileptic Drugs ◽  
Older Adult ◽  
Late Onset ◽  
Multivariate Logistic Regression Analysis ◽  
Prescribing Patterns ◽  
Convulsive Status Epilepticus ◽  
Tertiary Center ◽  
Symptomatic Seizures ◽  
Acute Symptomatic Seizures

ABSTRACT Background: Data on prescribing patterns of antiepileptic drugs (AEDs) to older adult inpatients are limited. Objective: To assess changes in prescribing patterns of AEDs to older adult inpatients with late-onset epilepsy between 2009-2010 and 2015-2019, and to interpret any unexpected patterns over the 2015-2019 period. Methods: Patients aged ≥60 years with late-onset epilepsy from a tertiary center were selected. Demographic data, seizure characteristics and etiology, comorbidities, and comedications were analyzed, in addition to prescription regimens of inpatients taking AEDs to treat epilepsy. AED regimens were categorized into two groups: group 1 included appropriate AEDs (carbamazepine, oxcarbazepine, valproic acid, gabapentin, clobazam, lamotrigine, levetiracetam, topiramate, and lacosamide); and group 2 comprised suboptimal AEDs (phenytoin and phenobarbital). Multivariate logistic regression analysis was performed to identify risk factors for prescription of suboptimal AEDs. Results: 134 patients were included in the study (mean age: 77.2±9.6 years). A significant reduction in the prescription of suboptimal AEDs (from 73.3 to 51.5%; p<0.001) was found; however, phenytoin remained the most commonly prescribed AED to older adult inpatients. We also found an increase in the prescription of lamotrigine (from 5.5 to 33.6%) and levetiracetam (from 0 to 29.1%) over time. Convulsive status epilepticus (SE) and acute symptomatic seizures associated with remote and progressive etiologies were risk factors for the prescription of suboptimal AEDs. Conclusions: Phenytoin was the main suboptimal AED prescribed in our population, and convulsive SE and acute symptomatic seizures associated with some etiologies were independent risk factors for phenytoin prescription. These results suggest ongoing commitment to reducing the prescription of suboptimal AEDs, particularly phenytoin in Brazilian emergence rooms.

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