Modified setting of negative pressure in children with mild respiratory disease.

BACKGROUND: Continuous negative extra-thoracic pressure (CNEP) can prevent children with apnea developing severe respiratory infection with endotracheal intubation. Little is known about children with mild acute respiratory disease, especially with a focus on clinical respiratory symptoms. METHODS: We conducted a prospective, observational study between July 2014 and July 2017 to evaluate the safety of a modified setting of CNEP in hospitalized children with symptoms of chest-wall retraction or nasal alar breathing without the requirement for immediate intubation therapy in a single center. A modified setting of CNEP was defined as 4 h of treatment comprising 3 consecutive hours of CNEP followed by 1 h of rest. RESULTS: We studied 19 hospitalized children with retraction or nasal breathing but no possible state of endotracheal intubation. The median age at admission was 0.9 years and the duration of CNEP was 6 days. No sedative drugs were used. The percentage of children with retraction or nasal breathing after 24 h from initiation of CNEP was significantly decreased compared with that just before CNEP (68% vs 100%, P = 0.02). Logistic regression showed no statistical evidence of contributing factors for pulmonary symptoms. No patients were transferred to receive intubation, but one boy reinitiated respiratory support within 6 months after discharge. No children had adverse events of upper airway obstruction, skin injury, interfering with access, hypothermia, discomfort from fitting a cuirass, and neck excoriation. CONCLUSIONS: Our results suggest that a modified setting of CNEP management can be tolerated and continued without concern of adverse events.

Late-onset epileptic spasms in a female patient with a CASK mutation.

We report a female patient with late-onset epileptic spasms (ESs) of a rare form, distinct from those seen in typical West syndrome, in association with a heterozygous frameshift CASK mutation (c.1896dupC (p.C633fs(∗)2)). She has a phenotype of microcephaly with pontine and cerebellar hypoplasia (MICPCH), and has had intractable ESs in clusters since 3 years 8 months of age with multifocal, particularly bifrontal, epileptic discharges in electroencephalogram. The available literature on patients with both ESs and CASK mutations has been reviewed, revealing that four of the five female children, including the present girl, had late-onset ESs, in contrast to the four males, who tended toward early-onset ESs.

A Japanese adult case of guanidinoacetate methyltransferase deficiency.

Guanidinoacetate methyltransferase (GAMT) deficiency is a rare disorder of creatine synthesis resulting in cerebral creatine depletion. We present a 38-year-old patient, the first Japanese case of GAMT deficiency. Developmental delay started after a few months of age with a marked delay in language, which resulted in severe intellectual deficit. She showed hyperactivity and trichotillomania from childhood. Epileptic seizures appeared at 18 months and she had multiple types of seizures including epileptic spasms, brief tonic seizures, atypical absences, complex partial seizures with secondary generalization, and "drop" seizures. They have been refractory to multiple antiepileptic drugs. Although there have been no involuntary movements, magnetic resonance imaging revealed T2 hyperintense lesions in bilateral globus pallidi. Motor regression started around 30 years of age and the patient is now able to walk for only short periods. Very low serum creatinine levels measured by enzymatic method raised a suspicion of GAMT deficiency, which was confirmed by proton magnetic resonance spectroscopy and urinary guanidinoacetate assay. GAMT gene analysis revealed that the patient is a compound heterozygote of c.578A>G, p.Gln193Arg and splice site mutation, c.391G>C, p.Gly131Arg, neither of which have been reported in the literature. We also identified two aberrant splice products from the patient's cDNA analysis. The patient was recently started on supplementation of high-dose creatine and ornithine, the effects of which are currently under evaluation. Although rare, patients with developmental delay, epilepsy, behavioral problems, and movement disorders should be vigorously screened for GAMT deficiency, as it is a treatable disorder.