Investigation of EEG changes before and after phototherapy in infants with severe hyperbilirubinemia.

BACKGROUND: Despite the known effect of hyperbilirubinemia in neonates, the effect of phototherapy on electroencephalography (EEG) remains unknown. Therefore, we aimed to determine the alteration of electroencephalography in infants with hyperbilirubinemia before and after phototherapy. METHODS: This cross-sectional study was performed on infants of≥35 weeks of gestation with hyperbilirubinemia. Information including age, sex, birth weight, hemoglobin levels, and treatment measures was recorded. In all studied infants, an EEG was performed before (in the first eight hours of hospitalization) and after treatment (after phototherapy or blood transfusion). The required duration of phototherapy, hospitalization and adverse effects were assessed then EEG of the neonates was compared before and after treatment. RESULTS: A total of 52 infants (44% female and 56% male) were included in this study. Mean gestational age, weight, and bilirubin were 38.6±1.53 weeks, 3150±625 g, and 23.87±4.36 mg/dl, respectively. The most common findings before phototherapy were Frontal Theta (21 patients, 40.4 percent) and Delta Brush (14 patients, 26.9%), while the most common findings after phototherapy were Frontal Theta (20 patients, 38.5%) and Delta Brush (19 patients, 36.5%). Mean±SD of bilirubin in infants with and without Delta Brush was 21.30±1.67 mg/dl and 19.95±0.94 mg/dl, respectively. CONCLUSIONS: Hyperbilirubinemia in newborns may be linked to altered EEG findings. After phototherapy, the Frontal theta was reduced, but the Delta brush was intensified. Bilirubin levels were higher in infants with Delta Brush in their EEG compared to infants without this finding.

Genetic and phenotypic characterization of NKX6-2-related spastic ataxia and hypomyelination.

BACKGROUND AND PURPOSE: Hypomyelinating leukodystrophies are a heterogeneous group of genetic disorders with a wide spectrum of phenotypes and a high rate of genetically unsolved cases. Bi-allelic mutations in NKX6-2 were recently linked to spastic ataxia 8 with hypomyelinating leukodystrophy. METHODS: Using a combination of homozygosity mapping, exome sequencing, and detailed clinical and neuroimaging assessment a series of new NKX6-2 mutations in a multicentre setting is described. Then, all reported NKX6-2 mutations and those identified in this study were combined and an in-depth analysis of NKX6-2-related disease spectrum was provided. RESULTS: Eleven new cases from eight families of different ethnic backgrounds carrying compound heterozygous and homozygous pathogenic variants in NKX6-2 were identified, evidencing a high NKX6-2 mutation burden in the hypomyelinating leukodystrophy disease spectrum. Our data reveal a phenotype spectrum with neonatal onset, global psychomotor delay and worse prognosis at the severe end and a childhood onset with mainly motor phenotype at the milder end. The phenotypic and neuroimaging expression in NKX6-2 is described and it is shown that phenotypes with epilepsy in the absence of overt hypomyelination and diffuse hypomyelination without seizures can occur. CONCLUSIONS: NKX6-2 mutations should be considered in patients with autosomal recessive, very early onset of nystagmus, cerebellar ataxia with hypotonia that rapidly progresses to spasticity, particularly when associated with neuroimaging signs of hypomyelination. Therefore, it is recommended that NXK6-2 should be included in hypomyelinating leukodystrophy and spastic ataxia diagnostic panels.