Pyridoxine-Dependent Epilepsy and Antiquitin Deficiency Resulting in Neonatal-Onset Refractory Seizures

Pyridoxine-dependent epilepsy (PDE) is an autosomal recessive neurometabolic disorder due to a deficiency of α-aminoadipic semialdehyde dehydrogenase (mutation in ALDH7A1 gene), more commonly known as antiquitin (ATQ). ATQ is one of the enzymes involved in lysine oxidation; thus, its deficiency leads to the accumulation of toxic metabolites in body fluids. PDE is characterized by persistent, recurrent neonatal seizures that cannot be well controlled by antiepileptic drugs but are responsive clinically and electrographically to daily pyridoxine (vitamin B6) supplementation. Although the phenotypic spectrum distinguishes between typical and atypical, pyridoxine-dependent is true for each. Diagnosis may pose a challenge mainly due to the rarity of the disorder and the fact that seizures may not occur until childhood or even late adolescence. Moreover, patients may not demonstrate an obvious clinical or electroencephalography response to the initial dose of pyridoxine. Effective treatment requires lifelong pharmacologic supplements of pyridoxine, and dietary lysine restriction and arginine enrichment should improve prognosis and avoid developmental delay and intellectual disability. The purpose of this review is to summarize briefly the latest reports on the etiology, clinical symptoms, diagnosis, and management of patients suffering from pyridoxine-dependent epilepsy.

Clinical profile, etiology, type and outcome of neonatal seizures: a hospital-based study

Background: Our study was undertaken to study the etiological factor, clinical profile, types and outcome of newborn with neonatal seizures (NNS).Methods: Our study was hospital based prospective study was done in Sheri Kashmir institute of medical sciences (SKIMS) Bemina from April 2013 to April 2015 in NICU, after obtaining ethical clearance from institutional ethical committee. All neonates fulfilling inclusion criteria were included in our study.Results: In our study, 80 neonates with seizures were included in our study, among them 48 were males and 32 were females. Majority of neonates (57.5%) developed seizures during first 72 hours of life due to birth asphyxia. Commonest types of neonatal seizures observed in our study were subtle observed in 46 cases, followed by tonic (21.2 %), clonic (14.9 %) and mixed (6.2%) seizures. Birth asphyxia was commonest cause (57.5%) of NNS, sepsis with meningitis (18.7%) followed by hypoglycemia (13.7%) and hypocalcemia (5%). Cases of birth asphyxia were associated with higher mortality (58.3%) as compared to cases with metabolic seizures.Conclusions: From our study we conclude that commonest cause of neonatal seizure was birth asphyxia occurring within 72 hours of birth. Sepsis and meningitis were also common infections resulting in neonatal seizure, while as hypoglycaemia and hypocalcemia were common biochemical abnormalities leading to NNS. Early identification and treatment are likely important for long-term outcomes in acute symptomatic seizure.

Parent Mental Health and Family Coping over Two Years after the Birth of a Child with Acute Neonatal Seizures

Little is known about parent and family well-being after acute neonatal seizures. In thus study, we aimed to characterize parent mental health and family coping over the first two years after their child’s neonatal seizures. Parents of 303 children with acute neonatal seizures from nine pediatric hospitals completed surveys at discharge and 12-, 18- and 24-months corrected age. Outcomes included parental anxiety, depression, quality of life, impact on the family, post-traumatic stress and post-traumatic growth. We used linear mixed effect regression models and multivariate analysis to examine relationships among predictors and outcomes. At the two-year timepoint, parents reported clinically significant anxiety (31.5%), depression (11.7%) and post-traumatic stress (23.7%). Parents reported moderately high quality of life and positive personal change over time despite ongoing challenges to family coping. Families of children with longer neonatal hospitalization, functional impairment, post-neonatal epilepsy, receiving developmental support services and families of color reported poorer parental mental health and family coping. Parents of color were more likely to report symptoms of post-traumatic stress and positive personal change. Clinicians caring for children with neonatal seizures should be aware of lasting risks to parent mental health and family coping. Universal screening would enable timely referral for support services to mitigate further risk to family well-being and child development.

Efficacy and Safety of Levetiracetam vs. Phenobarbital for Neonatal Seizures: A Systematic Review and Meta-Analysis

Background: Neonatal seizures are a common neurological emergency in newborns. Phenobarbital (PB) is the first-line antiepileptic drug (AED). However, PB has some side effects, such as hypotension and respiratory depression, and it can accelerate neuronal apoptosis in the immature brain. Levetiracetam (LEV), a new antiepileptic drug, has been used as a second-line drug for the treatment of neonatal seizures. Compared with PB, LEV has many advantages, including a low incidence of side effects and better neurodevelopmental outcomes. However, there are only a few systematic reviews of LEV for the treatment of neonatal seizures.Objective: To evaluate the efficacy and safety of LEV for neonatal seizures and to compare the efficacy, side effects, and neurological outcomes between LEV and PB in the treatment of neonatal seizures.Methods: The keywords LEV, PB, and neonatal seizure were searched in the MEDLINE, Cochrane Library, Web of Science, EMBASE, clinicaltrials.gov, and China National Knowledge Internet (CNKI) databases with a last update in July 2021 to collect high-quality studies. We collected studies studying the efficacy or safety of LEV and PB in the treatment of neonatal seizures applying strict inclusion and exclusion criteria. The data were extracted and outcome measures, including efficacy, side effect rate, neurological score, and mortality rate, were analyzed with RevMan 5.3 software.Results: Ten articles were finally included in the meta-analysis. The meta-analysis showed that there was no difference in efficacy between LEV and PB in the treatment of neonatal seizures. Compared with PB, the incidence of side effects of LEV was lower. The incidence of hypotension and respiratory depression in the LEV group was significantly lower than that in the PB group. In terms of long-term neurodevelopmental outcomes, there was no significant difference in the Bayley Scales of Infant Development (BSID) scores between LEV and PB.Conclusion: PB is still the first-line AED recommended by the WHO for the treatment of neonatal seizures. The new AEDs LEV may not have better efficacy than PB. At the same time, LEV is associated with better neurodevelopment outcomes and a lower risk of adverse effects. In addition, continuous EEG monitoring should be used to diagnose neonatal seizures to evaluate the severity of the seizures, remission, and drug efficacy.Systematic Review Registration: PROSPERO, identifier: CRD42021279029.