Super-refractory status epilepticus is a life-threatening condition. Resistance to benzodiazepine and barbiturate treatment for this disorder is thought to be due to internalization of synaptic γ-aminobutyric acid (GABA)A receptors, and withdrawal of benzodiazepines and barbiturates during treatment often triggers seizure recurrence. The neurosteroid allopregnanolone acts as a positive allosteric modulator of synaptic and extrasynaptic GABAA receptors. Here we describe the use of allopregnanolone in 2 pediatric patients with super-refractory status epilepticus. This treatment allowed the general anesthetic infusions to be weaned with resolution of status epilepticus. This is the first report of allopregnanolone use to treat status epilepticus in children.
Choline acetyltransferase catalyzes the synthesis of acetylcholine at cholinergic nerves. Mutations in human CHAT cause a congenital myasthenic syndrome (CMS) due to impaired synthesis of ACh; this severe variant of the disease is frequently associated with unexpected episodes of potentially fatal apnea. The severity of this condition varies remarkably, and the molecular factors determining this variability are poorly understood. Furthermore, genotype–phenotype correlations have been difficult to establish in patients with biallelic mutations. We analyzed the protein expression of seven ChAT mutations, p.Val136Met, p.Arg207His, p.Arg186Trp, p.Val194Leu, p.Pro211Ala, p.Arg566Cys and p.Ser694Cys, in HEK-293 cells to phosphorylated ChAT, determined their enzyme kinetics and thermal instability, and examined their structural changes. Three mutations, p.Arg207His, p.Arg186Trp and p.Arg566Cys, are novel, and p.Val136Met and p.Arg207His are homozygous in three families and associated with severe disease. The characterization of mutants showed a decrease in the overall catalytic efficiency of ChAT; in particular, those located near the active-site tunnel produced the most seriously disruptive phenotypic effects. On the other hand, p.Val136Met is located far from both active and substrate-binding sites produced the most drastic reduction of ChAT expression. Overall, CHAT mutations producing low enzyme expression and severe kinetic effects are associated with the most severe phenotypes.
BackgroundTo determine whether telemedicine improves access to outpatient neurology care for underserved patients, we compared appointment completion between urban, in-person clinics and telemedicine clinics held in rural and underserved communities where neurology consultations are provided remotely.MethodsIn this retrospective study, we identified patients scheduled for outpatient care from UCDH pediatric neurologists between January 1, 2009, and July 31, 2017, in person and by telemedicine. Demographic and clinical variables were abstracted from electronic medical records. We evaluated the association between consultation modality and visit completion in overall and matched samples using hierarchical multivariable logistic regression.ResultsWe analyzed 13,311 in-person appointments by 3,831 patients and 1,158 telemedicine appointments by 381 patients. The average travel time to the site of care was 45.8 ± 52.1 minutes for the in-person cohort and 22.3 ± 22.7 minutes for the telemedicine cohort. Telemedicine sites were located at an average travel time of 217.1 ± 114.8 minutes from UCDH. Telemedicine patients were more likely to have nonprivate insurance, lower education, and lower household income. They had different diagnoses and fewer complex chronic conditions. Telemedicine visits were more likely to be completed than either “cancelled” or missed (“no show”) compared with in-person visits (OR 1.57, 95% CI: 1.34–1.83; OR 1.66, 95% CI: 1.31–2.10 matched on travel time to the site of care; OR 2.22, 95% CI: 1.66–2.98 matched on travel time to UCDH).ConclusionsThe use of telemedicine for outpatient pediatric neurology visits has high odds of completion and can serve as an equal adjunct to in-person clinic visits.
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