Case report: Severe nonketotic hyperglycinemia in a neonate without apparent seizures but concomitant cleft palate and cerebral sinovenous thrombosis.

Nonketotic hyperglycinemia (NKH) is in most cases a fatal inborn error of metabolism which usually presents during the neonatal period as encephalopathy and refractory seizures. The reported congenital anomalies associated with NKH included corpus callosal agenesis, club foot, cleft palate, and congenital heart disease. Here, we report a newborn who presented with encephalopathy without overt seizures, cerebral venous sinus thrombosis, and cleft palate. Electroencephalography showed a burst suppression pattern, which suggests the etiology could be due to a metabolic or genetic disorder. The amino acid analysis of plasma and cerebrospinal fluid showed elevated glycine. Whole exome sequencing identified a heterozygous c.492C > G; p.Tyr164Ter variant in exon 4 of the GLDC gene inherited from the patient's father. Further long-read whole genome sequencing revealed an exon 1-2 deletion in the GLDC gene inherited from the patient's mother. Additional analyses revealed no pathogenic variants of the cleft palate-related genes. The cleft palate may be an associated congenital anomaly in NKH. Regarding cerebral venous sinus thrombosis, we found a heterozygous variant (p.Arg189Trp) of the PROC gene, which is a common cause of thrombophilia among Thai newborns. A neonate with NKH could present with severe encephalopathy without seizures. A close follow up for clinical changes and further next generation sequencing are crucial for definite diagnosis in neonates with encephalopathy of unclear cause.

Epidemiology and burden of Haemophilus influenzae disease in Thai children before implementation of the routine immunisation programme: A National Health Data Analysis.

OBJECTIVES: To conduct the first pre-Haemophilus influenzae (Hi) type b (Hib) immunisation programme-based epidemiological study using national health data. METHODS: We analysed National Health Security Office data, which cover 72% of the Thai population. The study population included children aged <18 years admitted for Hi disease from 2015 to 2019. Hi disease diagnosis and death were based on the International Statistical Classification of Diseases and Related Health Problems (10th revision) hospital discharge summary codes. We estimated the hospital cost per admission using diagnosis-related grouping with a global budget. RESULTS: A total of 1125 children aged <18 years were admitted for Hi disease. During the 5-year-study, the annual incidence of Hi disease varied from 1.5 to 1.9 per 100,000 children, with an overall case fatality rate (CFR) of 2%. Pneumonia was the most common clinical form, followed by meningitis and sepsis. The incidence, clinical forms and severity of Hi disease were age specific. Infant CFR was higher than that of other age groups. The incidence of Hi disease in children aged <5 years was 4.9 per 100,000 (CFR = 2.0%). Sepsis was the primary cause of infant death, whereas pneumonia was the cause of death in children aged >5 years. The hospital cost ranged from 25,000 to 30,000 THB per admission. CONCLUSIONS: This analysis provided epidemiological data of Hi in Thai children before the Hib routine immunisation programme. The incidence of Hi disease was lower than that previously speculated. Our results could facilitate an assessment of the impact of Hib immunisation programme in Thailand.

A multi-disciplinary clinic for SCN8A-related epilepsy.

OBJECTIVE: We endeavored to evaluate a cohort of patients diagnosed with SCN8A-related epilepsy in a multi-disciplinary clinic and to create a bio-repository. METHODS: We recruited patients with epilepsy due to SCN8A variants at Children's National Medical Center, through family organizations, or SCN8A.net. Study procedures included medical record review, review of EEG and MRI data, clinical evaluation, the Vineland Adaptive Behavior Scales, Third Edition (VABS-3), DNA extraction, and preparation of peripheral blood mononuclear cells. RESULTS: Seventeen patients (9 months - 19 years) completed the study. Age at seizure onset was 1 day to 4 years old (median age 4 months). Epilepsy phenotype ranged from mild epilepsy to severe developmental and epileptic encephalopathy. Medications targeting the voltage-gated sodium channel were most often effective, while levetiracetam resulted in worsening seizures and/or developmental regression in 7/16 (p < 0.05). VABS-3 scores were below age expectations for most children; older children had lower scores. Neurological examination revealed hypotonia (13), spastic quadriparesis (1), ataxia (9), dyskinesia (2)/ dystonia (7), and four non-ambulatory. CONCLUSIONS: This is the first report of a large series of patients with epilepsy due to SCN8A variants evaluated in a single multi-disciplinary clinic. By utilizing a more comprehensive and consistent evaluation, we clarify specific seizure and epilepsy types, describe a distinct epilepsy phenotype in a patient with a nonsense variant, delineate patterns of developmental delay, language, and swallow function (specifically anomic aphasia and flaccid dysarthria), identify and characterize movement disorders, report common findings on physical exam, and demonstrate clinical worsening with levetiracetam.

Increased cerebral blood flow on arterial spin labeling magnetic resonance imaging can localize to seizure focus in newborns: A report of 3 cases.

Arterial spin labeling (ASL) magnetic resonance imaging (MRI) can assess cerebral blood flow (CBF) without using radiolabeled tracers. It is unknown whether regional increases in CBF on ASL MRI correlate with seizure location in newborns. We report 3 newborns with focal seizures localized on continuous video electroencephalogram (cEEG), anatomical brain MRI, and ASL MRI. Each patient underwent pseudocontinuous ASL with segmented 3-dimensional fast spin echo readout as part of standard care. Case 1 is a term male infant presenting with left temporal status epilepticus and recurrent cEEG seizures from an idiopathic large left intraventricular hemorrhage. ASL images demonstrated left mesial temporal lobe increased CBF. Case 2 is a late preterm male infant presenting with recurrent cEEG seizures due to focal right megalencephaly. Ictal EEG and ASL images coincided with the focal dysplasia. Case 3 is a dysmorphic term female infant with nonconvulsive partial status epilepticus identified by focal increased CBF of the left temporal lobe on ASL images. The area of increased CBF was within an area of extensive left hemisphere dysplasia. To our knowledge, this is the first report of regional increases in CBF on ASL MRI correlating with ictal cEEG in newborns.