Neurological manifestations of SARS-CoV-2 infection in children in Taiwan: A cross-section, multicenter study.

BACKGROUND: The SARS-CoV-2 virus has been a global public health threat since December 2019. This study aims to investigate the neurological characteristics and risk factors of coronavirus disease 2019 (COVID-19) in Taiwanese children, using data from a collaborative registry. METHODS: A retrospective, cross-sectional, multi-center study was done using an online network of pediatric neurological COVID-19 cohort collaborative registry. RESULTS: A total of 11160 COVID-19-associated emergency department (ED) visits and 1079 hospitalizations were analyzed. Seizures were the most common specific neurological symptom, while encephalitis and acute disseminated encephalomyelitis (ADEM) was the most prevalent severe involvement. In ED patients with neurological manifestations, severe neurological diagnosis was associated with visual hallucination, seizure with/without fever, behavior change, decreased GCS, myoclonic jerk, decreased activity/fatigue, and lethargy. In hospitalized patients with neurological manifestations, severe neurological diagnosis was associated with behavior change, visual hallucination, decreased GCS, seizure with/without fever, myoclonic jerk, fatigue, and hypoglycemia at admission. Encephalitis/ADEM was the only risk factor for poor neurological outcomes at discharge in hospitalized patients. CONCLUSIONS: Neurological complications are common in pediatric COVID-19. Visual hallucination, seizure, behavior change, myoclonic jerk, decreased GCS, and hypoglycemia at admission are the most important warning signs of severe neurological involvement such as encephalitis/ADEM.

Update current understanding of neurometabolic disorders related to lysine metabolism.

Lysine, as an essential amino acid, predominantly undergoes metabolic processes through the saccharopine pathway, whereas a smaller fraction follows the pipecolic acid pathway. Although the liver is considered the primary organ for lysine metabolism, it is worth noting that lysine catabolism also takes place in other tissues and organs throughout the body, including the brain. Enzyme deficiency caused by pathogenic variants in its metabolic pathway may lead to a series of neurometabolic diseases, among which glutaric aciduria type 1 and pyridoxine-dependent epilepsy have the most significant clinical manifestations. At present, through research, we have a deeper understanding of the multiple pathophysiological mechanisms related to these diseases, including intracerebral accumulation of neurotoxic metabolites, imbalance between GABAergic and glutamatergic neurotransmission, energy deprivation due to metabolites, and the dysfunction of antiquitin. Because of the complexity of these diseases, their clinical manifestations are also diverse. The early implementation of lysine-restricted diets and supplementation with arginine and carnitine has reported positive impacts on the neurodevelopmental outcomes of patients. Presently, there is more robust evidence supporting the effectiveness of these treatments in glutaric aciduria type 1 compared with pyridoxine-dependent epilepsy.

CMAP changes upon symptom onset and during treatment in spinal muscular atrophy patients: lessons learned from newborn screening.

PURPOSE: Early identification and treatment of spinal muscular atrophy (SMA) are crucial but difficult. In this study, we aimed to assess the significance of compound motor action potential (CMAP) amplitude in patients identified through a newborn screening program. METHODS: We initiated a large-scale population newborn screening program for SMA in Taiwan in 2014. Patients had access to treatment through clinical trials or expanded use programs. Symptomatic patients were evaluated regularly, including CMAP exams. RESULTS: Among 364,000 screened newborns, 21 were diagnosed with SMA. The incidence of SMA was around 1 in 17,000 live births, and 70% developed SMA type 1. All infants with two SMN2 copies became symptomatic before the age of 1 month. CMAP amplitudes of 12 newborns were available, including 6 who were subsequently treated with nusinersen. We found that a rapid decrease of CMAP amplitude was an early predictor of symptom onset. Pretreatment CMAP and rapid increment of post-treatment CMAP could predict better treatment outcomes. CONCLUSION: This study prospectively demonstrated the incidence of SMA and its types. Our results imply the importance of pretreatment CMAP amplitude and rapid reversal of post-treatment CMAP amplitude with regard to disease presentation and also treatment outcomes.

The efficacy of perampanel in young children with drug-resistant epilepsy.

PURPOSE: Perampanel, a selective, noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) antagonist, has been approved as an effective and safe drug for the treatment of adults and adolescents with epilepsy. However, only a few studies have reported about the efficacy and tolerability of perampanel in children under 7 years old with refractory epilepsy. In this work, we aimed to describe our clinical experience in this group. METHODS: This single-center retrospective observational study was performed by reviewing the medical records of children below 7 years old with epilepsy and were treated with perampanel. RESULTS: A total 38 patients (19 females, 19 males) were enrolled, with a mean age of 4 ± 1.6 years (range, 0-6 years). The response rates (defined as 50 % seizure reduction) were 44 % and 31 % after 6 and 12 months of treatment, respectively, and the freedom of seizures was reached in 13 % and 10 % after the same treatment periods. The short- and long-term response rate in patients with tuberous sclerosis (TSC) and Dravet syndrome was high (67 %). The response rate in refractory spasms was 40 % at 6 months, but dropped to 13 % after 12 months of treatment. The retention rates were 61.1 % and 51.5 % at 6 and 12 months, respectively. Adverse events were reported in eight patients (22 %), which included emotional change (n = 4), lethargy (n = 2), nasal bleeding (n = 1), and drug allergy (n = 1). CONCLUSIONS: As a real-world pediatric case series, our study demonstrated the efficacy and tolerability of perampanel in young children with intractable epilepsy. In our experience, lower starting and maintenance dose of perampanel would be effective in the pediatric group. We also propose the use of perampanel as an effective therapy for epilepsy in children with TSC and Dravet syndrome.