By transitioning from a pediatrician to a pediatric neuropathologist, I have gained a unique position to approach pediatric neurological diseases from both clinical and pathological perspectives. This transition has dramatically expanded the scope of my work and interactions with professionals from different fields. Based on my experience, I will present the possibilities and challenges that come into view from this position, as well as future prospects. One of my initiatives involves regenerating pathological specimens from past pediatric neurological disease cases that underwent autopsies and creating a database of autopsy information. Through this effort, I have demonstrated the potential to gain new insights by regenerating specimens of rare diseases from the past and re-evaluating them with modern technology. Additionally, I am working in collaboration with the Department of Forensic Medicine to elucidate the pathophysiology of Sudden Unexpected Death in Infancy (SUDI). We have identified findings such as glial scarring in the inferior olivary nucleus of the medulla oblongata and pathogenic variants in arrhythmia-related genes. I am also focusing on the ethical and social issues associated with the widespread use of Non-Invasive Prenatal Testing (NIPT). I feel the importance of providing appropriate information to families facing NIPT results and the need for pathological verification of fetuses that were terminated as a result of NIPT. Transitioning to a different field as a medical professional is not merely a career change. At times, it can serve as a bridge between clinical practice and basic research, deepening our understanding of pediatric neurological diseases and potentially leading to the development of new diagnostic methods and treatments from fresh perspectives.

  Objective: The present study investigated the relationship between the severity of sensory processing disorder (SPD) and both the overall severity of autism spectrum disorder (ASD) and the severity of social communication difficulties in early childhood among individuals with ASD. Methods: The severity of ASD and social communication difficulties was assessed using the short version of the Japanese questionnaire, the Parent-interview ASD Rating Scale-Text Revision (PARS-TR, PARS), while the severity of SPD in patients with ASD was assessed using the Japanese version of the Sensory Profile^TM (SP). The presence or absence of a relationship between the scores of the short version of PARS and SP was investigated using Spearman’s rank correlation coefficient. Results: Twenty-six children with ASD were analyzed. A correlation was observed between the scores of the short version of PARS and the total scores of SP. Regarding the four quadrants of sensory sensitivity (Poor Registration, Sensation Seeking, Sensitivity to Stimuli, and Sensation Avoiding), correlations were found in the three quadrants : Sensation Seeking, Sensitivity to Stimuli, and Sensation Avoiding. In the evaluation based on sensory modalities, correlations were observed in the Auditory, Visual, Vestibular, Tactile, and Multisensory modalities. Therefore, correlations were noted across multiple sensory modalities. Similar results were also observed when the scores were limited to social communication difficulties in the short version of PARS. Conclusions: The severity of SPD in early childhood among individuals with ASD correlated with both the overall severity of ASD and the severity of social communication difficulties, as assessed by the short version of PARS. For children with high scores on the short version of PARS, it is necessary to consider the possibility of comorbid SPD and to provide medical care accordingly.

  Objective: Since the launch of melatonin granules, it has been widely prescribed to patients other than those with neurodevelopmental disorders aged 6-15 years, for whom clinical trials have been conducted. The use of melatonin granules was investigated using receipt data after its launch for children. Methods: Using data from 470 Diagnosis Procedure Combination facilities and 144 health insurance societies, from June 2020 to September 2022, we extracted the following information about patients who were prescribed melatonin granules : the number of prescriptions, patient age, disease name, prescription dose. Results: A total of 8235 patients were prescribed melatonin granules, including 4533 males and 3702 females. The median patient age was 11 years. Of these, 6222 patients (75.6%) were aged 6-15 years, and 2013 patients (24.4%) were in the age group, for which safety and efficacy of the granules had not been confirmed. Of the 8235 patients, 4064 patients (49.4%) had autism spectrum disorder, 2331 patients (28.3%) had ADHD, 938 patients (11.4%) had intellectual ability disorder, 508 patients (6.2%) had motor disorders, 431 patients (5.2%) had communication disorders, 192 patients (2.3%) had focal learning syndrome, 1313 patients (15.9%) had other neurodevelopmental disorders, and 1536 patients (18.7%) had non-neurodevelopmental childhood disorders. Their minimum and maximum ages were 0 and 68 years, respectively. The minimum prescribed dose was as low as 0.5 mg, and the maximum prescribed dose was 7-9 mg. Conclusions: Melatonin granules were often prescribed to patients other than those with neurodevelopmental disorders aged 6-15 years. If we can examine the efficacy of melatonin granules in different patients with different insomnia symptoms, we can propose more detailed dosage and administration.

  In 2007, anti-N-methyl-d-aspartate (NMDA) receptor encephalitis was proposed as a paraneoplastic autoimmune encephalitis associated with ovarian teratomas, primarily affecting young females. Recently, the number of pediatric cases has increased. Owing to the treatable nature of immune-mediated encephalitis, early establishment of diagnostic methods and treatment strategies is necessary. There have been few reports of pacemaker implantation for autonomic nervous system symptoms in pediatric cases. Our report presents the case of 9-year-old girl with anti-NMDA receptor encephalitis who underwent emergency pacemaker implantation for severe bradycardia caused by autonomic symptoms. To the best of our knowledge, this is the youngest reported patient to date. The patient presented with psychiatric symptoms and altered consciousness and was diagnosed with autoimmune encephalitis based on an increased cerebrospinal fluid cell count. Immunotherapy was promptly initiated ; however, from Day 8 she required intensive care management due to central hypoventilation. We performed ovarian tumor-debulking surgery on Day 9 and confirmed the presence of anti-NMDA receptor antibodies in the cerebrospinal fluid on Day 10, leading to a definitive diagnosis of anti-NMDA receptor encephalitis. Bradycardia and atrioventricular block caused by autonomic nervous system symptoms necessitated plasma exchange therapy, which was initiated on Day 13. Furthermore, cardiopulmonary resuscitation was repeatedly performed owing to severe bradycardia and hypotension. On Day 17, we performed emergency pacemaker implantation. Even in pediatric cases, where early diagnosis and treatment are possible, the risk of life-threatening complications due to autonomic nervous system symptoms necessitates careful management and intervention.

  Hemimegalencephaly is a congenital disorder of brain formation. The most common presentation of hemimegalencephaly is epilepsy, which is often refractory to medical treatment ; consequently, early neurosurgical treatment is recommended. In this report, we discuss a case of hemispherotomy performed on a 3-month-old child with hemimegalencephaly and hypomelanosis of Ito, but the seizures did not improve, and the child subsequently developed hydrocephalus. Reports of patients with hemimegalencephaly who underwent hemispherotomy in early infancy, similar to this case, are limited to case reports. We reviewed the previous reports to examine postoperative complications, seizure prognosis, and developmental outcome. We found that patients who were operated on at ＜5 months of age had more congenital anomalies than those operated on after 5 months of age ; however, they had fewer postoperative complications. There were no significant differences in the prognosis of seizures and development. These results suggest that hemispherotomy for hemimegalencephaly does not increase postoperative complications, even at ＜5 months. In the present case, although it was anticipated that hemispherotomy would relieve clinical seizures originating from the right hemisphere, it did not alleviate the epileptic seizures, which affected both the affected and unaffected sides of the brain. We hypothesized that the accompanying neurocutaneous syndrome, hypomelanosis of Ito, in our patient may have affected the outcomes ; consequently, we investigated postoperative complications, seizure prognosis, and developmental prognosis in reported cases with and without the neurocutaneous complications. In the present study, there was no significant difference in postoperative complications, seizure prognosis, and developmental prognosis among patients with neurocutaneous syndrome compared with those without neurocutaneous syndrome.

  We report three cases of Dravet syndrome treated with fenfluramine hydrochloride (FFA). While good seizure control was achieved, they all presented with significant appetite loss, diarrhea, and weight loss, with the QOL of the patient and care givers deteriorated ; consequently, a change in treatment strategy was required. Case 1, a 12-year-old female, was treated with the initial dose of 0.2 mg/kg/day of FFA ; the dosage was reduced to 0.13 mg/kg/day because of frequent diarrhea and ill humor that deteriorated the QOL of the patient and her parents. Case 2, a 5-year-old boy, was treated with the initial dose of 0.1 mg/kg/day of FFA. He lost 13% of his body weight within 2 months caused by diarrhea and appetite loss ; FFA was thus discontinued. Case 3, a 2-year-old girl, presented with 9.1% weight loss caused by diarrhea and appetite loss with the dose of 0.3 mg/kg/day of FFA ; FFA was consequently discontinued. FFA causes specific side effects such as pulmonary hypertension and valvular disease. Those side effects attract much attention, and precautionary measures are conducted ; however, in fact, they rarely occur clinically. On the other hand, the frequently observed side effects such as decreased appetite, diarrhea, and weight loss also require careful attention, but there have been few reports focused on these side effects. In all cases reported here, parents were reluctant to discontinue or reduce the dosage of FFA given its effectiveness in seizure control. With the great demand for FFA for intractable seizures in developmental epileptic encephalopathy, the management of commonly observed side effects, such as gastrointestinal problems, may be worth more attention.

  Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a relatively rare inflammatory central nervous system demyelinating disease. Here, we present five cases of MOGAD, which we experienced during a 3-month period. Case 1 : A 10-year-old boy presented with rapidly progressive bilateral visual loss. Contrast-enhanced brain MRI revealed contrast enhancement surrounding the bilateral optic nerves. His intracranial pressure was markedly elevated. The differential diagnoses included optic neuritis, optic perineuritis, and idiopathic intracranial hypertension. Case 2 : A 4-year-old boy developed acute disseminated encephalomyelitis during the evaluation of a prolonged fever. Case 3 : A 4-year-old girl developed a prolonged fever. Contrast-enhanced brain MRI revealed bilateral optic neuritis, multiple lesions in the brain, and leptomeningeal enhancement. Cerebrospinal fluid analysis showed pleocytosis. Case 4 and case 5 involved patients who presented with optic neuritis. All five patients were eventually diagnosed with MOGAD. Two of the five patients had preceding respiratory infection. One of the other patients had nonspecific prodromal symptoms that could have been caused by infection. All cases occurred after the Japanese government relaxed infection control measures against coronavirus infection 2019, reclassifying it as Class 5. The change may have facilitated the spread of viruses in general, possibly causing an increased incidence of immune-mediated diseases. The true epidemiology of MOGAD, including mild and atypical cases, may become clear in the future as disease awareness increases and MOG antibody testing becomes more widespread.

  Cyclopentolate hydrochloride is an anticholinergic drug used as a paralytic agent during examinations for refractive errors, strabismus, and amblyopia. It has been reported to cause side effects such as drowsiness, hyperemia, and hallucinations. We encountered a case of convulsive seizures after administration of cyclopentolate hydrochloride, as its rare side effect. We describe a 5-year-old girl with trisomy 18 associated with congenital heart disease, hepatoblastoma, and febrile seizures. During her visit to the ophthalmologist for follow-up of amblyopia, cyclopentolate hydrochloride (1%) eye drops were applied three times to both eyes. Thirty minutes after the last application, she experienced focal clonic convulsions involving the face and extremities. Although diazepam suppository was ineffective, intravenous phenobarbital achieved seizure cessation. She was discharged without sequelae on day six after admission. Physicians should pay careful attention to the possibility of developing seizure following cyclopentolate hydrochloride administration in infants and children with convulsive predisposition.

  Many cases of human parechovirus (HPeV) infection have been reported to present with sepsis-like symptoms in neonates and infants and to progress to multiple organ damage and central nervous system symptoms, leading to severe illness. There are a cetrain number of cases in which brain magnetic resonance imaging (MRI) shows abnormal lesions mainly in the white matter, leading to the diagnosis of acute encephalitis. In the present study, we detail our experience with two cases of HPeV detected using Film Array^® Meningitis/Encephalitis (ME) Panel, in whom cerebrospinal fluid (CSF) analysis revealed no elevation in cell count or protein levels, visiting a medical facility for a fever in the neonatal period. In one case, HPeV type 3 was later proven in cerebrospinal fluid (CSF) by real-time polymerase chain reaction. In both cases, neopterin in CSF was elevated and brain MRI showed subtle lesions in the cerebral white matter and corpus callosum ; however, there were no central nervous system symptoms such as convulsions or disturbance of consciousness, and no neurological abnormalities were evident on physical examination. Both patients had no obvious permanent disability at the time of discharge from the hospital, and we considered these cases to be a mild form of HPeV encephalitis. It is considered necessary to study the epidemiology of HPeV encephalitis including the mild-form cases diagnosed by FilmArray, and the long-term developmental prognosis of these cases.