Punctate white matter lesions in full-term infants with neonatal seizures associated with SLC13A5 mutations

10.2174/1381612823666170809115827

“…Some improvement in response to drugs that affect GABA signaling, including including diazepam, lorazepam, phenobarbital, clonazepam, clobazam and midazolam, and sodium channel blockers, including phenytoin, lamotrigine and lidocaine, has been reported. However, phenytoin worsened myoclonus in one patient [343,344]. Acetazolamide decreases urinary citrate excretion by inducing metabolic acidosis [345], and this should increase citrate reabsorption by the renal NaDC1 transporter (SLC13A2) [346]: it was reported to improve seizure control without evidence of acidosis [343].…”

“…As astrocytes secrete citrate into extracellular medium, the potential function of SLC13A5 in neurons is to mediate the uptake of circulating citrate and astrocyte-released citrate for subsequent metabolism [340]. The phenotype of SLC13A5-related epileptic encephalopathy is characterised by seizure onset within the first weeks after birth, developmental delay, slow progression of motor function, significant impairment in language and speech development, fever sensitivity, early occurrence of status epilepticus (hemiconvulsive, convulsive and non-convulsive), defects in tooth development, and punctate white matter lesions on neonatal MRI (no longer visible at the age of 6 months, but lead to gliotic scarring visible on MRI at the age of 18 months) [341][342][343][344]. Three patients reportedly 'responded well' to ketogenic diet, although they had to stop the diet due to side effects or compliance issues, whilst four had seizure worsening or no benefit from the diet [342][343][344].…”

The brain's kryptonite: Overview of punctate white matter lesions in neonates

“…It is postulated that PWML identified during the first weeks of life result in early glial scarring or necrosis with mineralization at TEA (Wagenaar et al, 2017). Indeed, in full‐term infants suffering from neonatal seizures set off by bi‐allelic SLC13A5 mutations, PWML disappeared at the age of 6 months and were replaced by gliotic scarring, visible on MRI scans at the age of 18 months (Weeke et al, 2017).…”

A Distinctive Ictal Amplitude-Integrated Electroencephalography Pattern in Newborns with Neonatal Epilepsy Associated with <b><i>KCNQ2</i></b> Mutations

“…A stepwise diagnostic approach needs to prioritize the identification of treatable causes [4]. With the recent developments in neuroimaging techniques, the incidence of seizures of unknown etiology has decreased, and genetic defects are increasingly being recognized as an etiology of neonatal seizures [4,5] . Mutations in KCNQ2 , encoding the voltage-gated potassium channel Kv7.2, were first described in autosomal dominant benign familial neonatal seizures (BFNS) a self-limiting form of neonatal epilepsy with favorable outcome [6] .…”