Mitochondrial disorders cause various organ abnormalities. Consequently, the clinical presentation and disease concept are highly variable, making it difficult to diagnose. Because mitochondrial disorders are caused by abnormal respiratory chain enzyme complexes, biochemical diagnosis by examining respiratory chain enzyme activity and quantitatively or qualitatively evaluating protein complexes is important. However, genetic diagnosis is critical for determining treatment according to etiology and genetic counseling. Unfortunately, genetic diagnosis is not easy because of the following reasons : mitochondrial and nuclear DNAs are involved in the biogenesis of mitochondrial respiratory chain complexes, the pathogenicity of novel mitochondrial DNA mutations is difficult to evaluate, and causative genes cannot be identified even though nuclear DNA abnormality is suspected. Regarding the diagnosis of mitochondrial DNA mutations, it is important to pay attention to heteroplasmy, where the mutation rate varies depending on organ involvement. Nuclear DNA abnormalities are also observed in respiratory chain complexes and other factors involved in biogenesis, including respiratory chain assemblies. Although there are many types of etiologies of mitochondrial disorders, increasing numbers of causative genes have recently been discovered using next-generation sequencing, and patient diagnosis is progressing. In order to make the use of these genetic analyses, first of all, careful physical examination with an understanding of diverse clinical symptoms and types of mitochondrial diseases as well as a record of exhaustive medical history is required. Mitochondrial abnormalities should also be accurately diagnosed by comprehensive special examinations, such as biochemical and pathological evaluations, followed by appropriate clinical tests. The future treatments that correspond to individual and patient-specific disease etiologies require an accurate diagnosis and understanding of the disease mechanisms.
Congratulation on the publication of the 50th anniversary issue of No to Hattatsu as 4th editorial chairperson. The Journal was put on track by the dedicated contribution of Prof Yukio Fukuyama, Honorary President of the Japanese Society of Child Neurology. The development of the Journal, an institutional journal of the society, is traced from its beginnings as an idea in the mind of the first chief editor, Prof Fukuyama, through 50 years of publication. The urgency of a professional journal to child neurologists push to publish the Journal in 1969, and Prof Fukuyama has served since then as a chief editor and others interested the connections to the neurosciences and new technologies in the child development and disorder.The journal processes original papers, case reports, short communications, review articles, various committee reports including board meeting note, editorial board meeting, interview with delegates by the chairperson.
Objective: The therapeutic and medical social effects of ketogenic diet (KD) in children with epilepsy were examined. Methods: A retrospective study was conducted in 53 patients (mean start age 8.2 months, range 0.1-50 months) with intractable epielpsy, who were treated by KD with ketone formula. Results: Seizure-free rate was 11.3% (6/53) in all patients, 100% (3/3) in glucose trasporter 1 deficiency syndrome (GT-1D) patients, 16.7% (1/6) in syptomatic generalized epilepsy patients, and 13.3% (2/15) in symptomatic localization-related epilepsy patients. The proportion of patients who continued KD was 34% (18/53) in all patients, 100% (3/3) in patients with GT-1D, 50% (3/6) in patients with symptomatic generalized epilepsy, and 30% (3/10) in patients with Dravet syndrome. The duration (mean±SD) of KD was 663.0±717.3 days. After the initiation of KD, hospital stay, visit of emergency ambulance, and use of ambulance car were reduced, and days of attending school, kindergarten, etc. were increased in some patients. Motor developmental score increased in 8 patients, and cognitive developmental score in 7 patients. Conclusions: Use of KD in children was effective for inhibition of epileptic seizures in some patients with intractable epilepsy
Objective: We examined the clinical features of pediatric patients with Mycoplasma pneumoniae-associated encephalitis/encephalopathy. Methods: We retrospectively evaluated 0-15-year-old patients hospitalized for M. pneumoniae-associated encephalitis/encephalopathy to our hospital or to an affiliated hospital between 2010 and 2016. Results: There were six males and two females aged 2-14 years. They were categorized into two groups : early-onset type (n=2) in which neurological sympoms developed within 3 days of fever or cough onset and late-onset type (n=6) in which neurological symptoms developed 10 days after their onset. The early-onset group included two patients with mild encephalitis with a reversible splenial lesion (MERS). The late-onset group included three patients with autoimmune limbic encephalitis, one with acute disseminated encephalomyelitis, one with Bickerstaff’s brainstem encephalitis, and one with unclassified encephalopathy. Although these six patients completely recovered without sequela, dysarthria persisted in one patient with MERS and cerebellar lesions. Mild intellectual impairment persisted in one patient with limbic encephalitis. Conclusion: As prodromal respiratory symptoms were not outstanding in some studied patients, M. pneumoniae infection should be considered in patients with encephalitis/encephalopathy of unknown etiology. Although there are few clinical reports from Japan, further clinical investigations are expected given the recent development of sensitive diagnostic procedures such as loop-mediated isothermal amplification assay.
A 10-day-old boy was hospitalized who presented with fever nine days after birth, and repetitive seizures and central apnea appeared the following day. Diffusion-weighted images of MRI revealed symmetrical characteristic lesions spread throughout the white matter, which suggested human parechovirus type 3 (HPeV-3) encephalitis. Laboratory findings showed abnormality of coagulation, increase of ferritin and neopterin in serum, and neopterin in cerebrospinal fluid without pleocytosis. The patient was treated with intravenous dexamethasone for ten days, because hypercytokinemia was thought to be an important aggravating factor of brain damage. Cystic changes were observed only in the frontal area, but the other white matter lesions diminished. On the twenty-seventh day after onset, he was discharged without neurological deficit. HPeV-3 was detected in the blood, nasal discharge, and cerebrospinal fluid by real-time PCR. Moreover, transverse venous thrombosis was observed at onset, but diminished rapidly by anticoagulation treatment. Immunomodulating treatment using corticosteroids should be considered to prevent the deterioration of brain damage in patients with HPeV-3 encephalitis accompanied by hypercytokinemia.