The International Classification of Headache Disorders, third edition (2018) defines “migraine aura-triggered seizure” as a seizure occurring in a patient with migraine with aura during or within 1 hour after an attack of migraine with aura. This is a rare condition that causes a headache prior to an epileptic seizure and corresponds to the concept historically called “migralepsy”. Migralepsy is characterized by the temporal sequence of “headache-epileptic seizures”, and much attention has been focused on the pathology of the preceding headache. Parisi et al. interpreted the preceding headache as an epileptic seizure rather than a migraine. That is, they understood it as “headache=epileptic seizure” and named this seizure “ictal epileptic headache”, which is an epileptic seizure characterized by headache as the only symptom. Few reports of electroencephalography (EEG) studies have confirmed that a headache can be an epileptic seizure based on findings during the headache attack. On the other hand, some reports have used the term “epileptic headache” even though no ictal changes in EEG were observed during the attacks. The findings in those papers are considered to correspond to merely the interictal EEG abnormalities. We do not agree with the interpretation of the EEG findings presented in the various articles, even those published in mainstream international journals. Further EEG studies are needed to elucidate the pathophysiology of migralepsy. Currently, refraining from the easy interpretation of “EEG abnormality=epileptic seizure” is needed, and detailed verification is required from the perspective of epileptology.

  Cerebrotendinous xanthomatosis is a rare autosomal-recessive disorder caused by a decrease in sterol 27-hydroxylase activity, which disturbs bile acid synthesis and leads to cholestanol accumulation in multiple organs. Neurological symptoms and tendon xanthomas that progress in adulthood are the main symptoms of the disease. Although other signs of cerebrotendinous xanthomatosis, including persistent neonatal jaundice, developmental delays, psychiatric symptoms, refractory diarrhea, juvenile cataracts, and epileptic seizures, can be observed in childhood, they are often unrecognized due to their nonspecific nature. Accordingly, the recently introduced Suspicion Index has become a useful tool for the early detection of cerebrotendinous xanthomatosis. Serum cholestanol concentration should first be measured in suspected cases, followed next by genetic confirmation of a CYP27A1 gene mutation. After diagnosis, serum cholestanol concentration can be reduced by chenodeoxycholic acid treatment to improve neurological prognosis. Prompt diagnosis and treatment of cerebrotendinous xanthomatosis during childhood with the Suspicion Index is important before the appearance of neurological symptoms.

  Objective: Guideline Committee of the American Epilepsy Society recommends lorazepam therapy as first-line treatment for patients with status epilepticus. However, there are limited studies on lorazepam therapy for children with status epilepticus in Japan. We evaluated the efficacy and safety of intravenous lorazepam therapy for status epilepticus and repetitive seizures in children with epilepsy. Methods: We retrospectively evaluated the efficacy and safety of intravenous lorazepam therapy in children with epilepsy who developed status epilepticus and repetitive seizures from the Saitama Children’s Medical Center between April 2019 and November 2021. We enrolled 37 occurrences (19 males) and analyzed age, etiologies, seizure type, dose of lorazepam, and adverse effects. We compared these factors between responders and non-responders. Response was observed as a cessation of seizures for>12 hours after lorazepam infusion. Results: The median age at lorazepam infusion was 2.5 (range 0.3-17.7) years old. The most common etiology was genetic (n=12), and the most common seizure type was focal to bilateral tonic-clonic seizures (n=15). The median total dose of lorazepam was 0.050 (0.045-0.112) mg/kg. The responses in cases of status epilepticus and repetitive seizures were observed in 12/18 (67%) and 5/19 (26%) occurrences respectively. A decrease in SpO₂ was observed on one occurrence, however no serious adverse effects occurred. The number of status epilepticus in responders were significantly larger than that in non-responders (p<0.05). Conclusions: Lorazepam therapy was useful for status epilepticus in children with epilepsy. This therapy can be used safely if respiratory depression is carefully monitored.

  Objective: Lacosamide (LCM) is a novel antiepileptic drug that selectively promotes the slow inactivation of sodium channels. Few studies reported on the use of LCM in pediatric patients in Japan. This study investigated the efficacy and safety of LCM in the treatment of epilepsy in children. Methods: This study included patients with epilepsy who were prescribed LCM at the Department of Neurology, National Center for Child Health and Development between October 1, 2017 and May 31, 2021. Efficacy and safety were evaluated by stratifying patients according to seizure type, epilepsy type, epilepsy syndrome, etiology, presence of concomitant medications, and age (<16 years and ≥16 years). Results: A total of 118 patients (62 males) with a mean age of 12.4 years (range, 1 year and 7 months to 36 years) were selected. The overall efficacy rate was 37%, and the incidence of side effects was 4%. The efficacy for focal onset seizure was higher than that for focal to bilateral tonic-clonic seizure in patients younger than 16 years. The efficacy of focal epilepsy was higher than that of combined generalized and focal epilepsy in both patients younger and older than 16 years. Conclusions: LCM is effective and safe in the treatment of childhood-onset epilepsy in Japan, as previously reported. LCM may be more effective in the treatment of focal seizures other than bilateral tonic-clonic seizures, and focal epilepsy.

  Objective: The Medical Safety Committee of the Japanese Society of Child Neurology published “Recommendations for Criteria for Examining CT for Head Trauma in Children” (Recommendations) in 2019. Subsequently, revisions in the medical fees were made in 2020, and the change in requirements of medical fees related to CT examinations for pediatric head trauma was done. The present study aims to determine whether physicians are aware about the recommendations and the change in requirements of medical fees related to CT examinations for pediatric head trauma, and whether they apply the diagnostic algorithms for pediatric head trauma in Japan. We also identified factors related to the awareness and application of the diagnostic algorithms. Methods: We surveyed 7,590 physicians who treat pediatric head trauma in Japan through a web-based questionnaire. Statistical analysis was performed using a decision tree analysis and logistic regression model. Results: A total of 1,073 physicians participated in the survey (14.1% response rate). The survey respondents were male (75.2%), female (24.8%), pediatricians (65.6%), neurosurgeons (19.0%), pediatric emergency physicians (6.1%), pediatric surgeons (5.3%), radiologists (3.2%), and other physicians (0.8%). 64.6% of the physicians acknowledged the recommendations, and the factors related to this were department and position (p<0.001). Only 14.5% of physicians recognized the additional requirements. Moreover, only two-thirds of these physicians were able to implement them at their hospitals. The physicians who treated more than 6 trauma cases per month and worked at clinical training hospitals recognized the additional requirements and application of the diagnostic algorithms (p<0.001). Conclusion: The diagnostic algorithms for pediatric head trauma should be utilized in medical practice to reduce radiation exposure in children. It is necessary to widely inform diagnostic algorithm to physicians through various media since the previous recommendations and revisions in the medical fees for head trauma have not been sufficient.

  We herein present the ataxia telangiectasia (AT) of a 2-year-old boy who presented with celebellar ataxia and involuntary movements in early infancy was diagnosed early by blood tests. The patient had no developmental delay until the start of walking. He was admitted to our department because of persistent unsteadiness in walking. His gait was unsteady, and he proceeded in rushing to keep his balance. He was prone to falling over. In addition, athetosis-like undulating movements of the fingers were observed when grasping objects. Blood tests showed high alpha-fetoprotein, low IgG, low IgG2, and genetic tests revealed abnormal frameshifting〔NM_000051.3 (ATM) : c.1402_1403del [p.Lys468Glufs＊18] ; rs58771347〕and splicing variants〔NM_000051.3 (ATM) : c.8585-1G>A ; rs876660066〕of the ATM gene, which confirmed the diagnosis of AT. Early diagnosis of AT is challenging because the neurological symptoms are diverse and the characteristic telangiectatic symptoms appear in late infancy. And also, appropriate follow up for not only neurological manifestations but also for complications such as susceptibility to infection and malignancy is important at the point of life prognosis. Serological testing of children who present with involuntary movements in addition to cerebellar ataxia symptoms can lead to early diagnosis.

  Reversible splenial lesion syndrome (RESLES) is associated with varied etiologies and typically presents with various clinical features and neurological symptoms. We present an acute myeloid leukemia (AML) patient who was diagnosed as having RESLES by a brain MRI screening in spite of no clear symptom. This previously healthy 15-year-old girl presented with dizziness upon standing for the past 9 days and fatigue while standing for the past 5 days. On admission, her consciousness was clear, and there was no abnormal neurological finding. She was diagnosed with AML, because she had anemia and infiltration of 1% blast cells in the peripheral blood. There were no leukemic cells in the cerebrospinal fluid. Antibiotics and antifungal agents were immediately administered, and she underwent transfusion for anemia. She had a transient fever of 37.5-38℃ on the first and second days of admission during the blood transfusion. Post-treatment, her symptoms of dizziness and fatigue improved. On the eighth day of admission, brain MRI revealed hyperintensity on diffusion-weighted imaging in the splenium of the corpus callosum. Follow-up MRI revealed resolution of the splenium lesion. From the clinical course of malignancies, such as AML, various causes, such as blood transfusion, CNS infiltration, medication, and infections due to immunosuppression, can be assumed. In this case, blood transfusion may have been the etiologic factor for RESLES after a detailed consideration of the clinical course and the period of transient fever due to blood transfusion up until MRI revealed the splenial lesion. Therefore, it is necessary to carefully monitor the clinical course of such patients.

  Levetiracetam (LEV) is one of the least teratogenic anticonvulsants with comparatively low mutagenicity and is thus often the first-choice drug for women of childbearing age with epilepsy. While the high breast milk transfer rate of LEV is widely known, much remains unknown about its role as a potential risk factor for neonatal abstinence syndrome (NAS). We experienced two cases in which neonates presenting with NAS were born to mothers receiving LEV treatment. In both cases, no abnormalities in fetal development or pulse monitoring were observed during gestation, and asphyxia did not occur. However, from 1 hour post-birth onward, the two neonates presented with maximum NAS scores of 4 points (lethargy, tachypnea, and poor feeding) and 8 points (lethargy, hypotonia, apnea, and tachypnea), necessitating intensive care, including tracheal intubation. Drug transfer to the fetus during pregnancy is unavoidable even for drugs that are believed to be relatively safe, hence neonates must be monitored carefully. Regardless of the stability of the pregnancy course or the absence of asphyxia, physicians must be aware of the possibility of NAS onset in infants born to mothers taking certain medications. Sufficient preparation for resuscitation and proper management until the stabilization of feeding behavior are necessary.

  Methotrexate (MTX) -related leukoencephalopathy presents with encephalopathy symptoms and white matter lesions on brain MRI after administration of MTX. Most of the patients show transient symptoms and MRI findings. However, there are no reports of detailed functional evaluation of this condition. Herein, we report a case of MTX-related leukoencephalopathy that was functionally evaluated with SPECT during the acute and convalescent phases. The patient had received anticancer drug treatment for lymphoma at his ago of 14 years. At age 15, he developed dysarthria and bilateral upper limb paresis 5 days after intrathecal administration of MTX. He was diagnosed with MTX-related leukoencephalopathy due to the high signal intensity in the left centrum semiovale on brain MRI. Since the symptoms disappeared within 2 weeks, additional intrathecal MTX was administered. However, he showed dysarthria and paresis of the left upper limb on the 23^rd day and disturbance of consciousness, dysphagia, and tetraparesis on the 55^th day. On the 65^th day, ethyl cysteinate dimer (ECD) -SPECT demonstrated diffuse hypoperfusion in the bilateral cerebral cortex, while iomazenil (IMZ) -SPECT showed no decrease of benzodiazepine receptor accumulation. In 4 weeks, dysarthria, disturbance of consciousness, dysphagia, and tetraparesis disappeared with the recovery of cerebral blood flow in ECD-SPECT. IMZ-SPECT showed normal findings in the convalescent phase as well. We suspended the administration of MTX, and he achieved remission at the age of 19 without neurological sequelae. MTX-related leukoencephalopathy may show transient dysfunction of the central nervous system without loss of neuronal cells.

  Recent studies have confirmed the efficacy and safety of rituximab (RTX) for the treatment of pediatric anti-N-methyl-D-aspartate (NMDA) receptor encephalitis, but reports of its use in Japan are still rare. We report the case of a 4-year-old girl who developed resistance to intravenous methylprednisolone therapy (IVMP) and intravenous immunoglobulin therapy, (IVIG) but had a marked response to RTX administration. Additionally, a 13-year-old boy with anti-NMDA receptor encephalitis coexisting with anti-myelin oligodendrocyte glycoprotein antibody responded to IVIG, IVMP and intravenous cyclophosphamide therapy respectively, but experienced recurrence. He was treated with RTX along with mycophenolate mofetil to prevent recurrence. Early administration of RTX is effective in suppressing recurrence, and its use is increasing worldwide. It should be actively considered in cases resistant to 1st line treatment and in cases of recurrence.

  This case report presents four patients who developed vigabatrin-associated brain abnormalities on MRI (VABAM) after vigabatrin (VGB) for infantile spasms (IS). Case 1 was a 17-month-old girl who developed IS of unknown etiology at 4 months. VGB was started at 9 months. VABAM was not observed in the first and fifth months after VGB start, but in the eighth month hyperintensities were observed in the central tegmental tract (CTT) on T2-weighted images (T2WI) and in the thalami on T2WI and diffusion-weighted images (DWI) without symptom. VGB withdrawal completely cleared these findings. Case 2 was a 6-month-old girl who developed IS of unknown etiology at 1 month. VGB was started at 5 months. One month after VGB start, DWI and T2WI hyperintensity was observed in the anterior commissure (AC) and globus pallidi (GP) without symptom, and treatment proceeded. Two months after VGB start : twelve days after corpus callosotomy, hypertension and new signal abnormalities in the thalami were seen. These abnormalities disappeared after VGB reduction. Case 3 involved a 13-month-old boy with cerebral palsy due to hypoxic-ischemic encephalopathy who developed IS at 4 months. VGB was started at 1 year old. One month after VGB start, imaging revealed T2WI and DWI hyperintensities in the putamens, GP and CTT, and DWI intensities in the AC and thalami without symptom. These tended to improve with VGB withdrawal. Case 4 was a 14-month-old boy with trisomy 21 who developed IS at 11 months. VGB was started immediately and discontinued as myoclonic seizures worsened. After VGB withdrawal : one month after VGB start, MRI revealed DWI hyperintensities in the GP, AC, and fornixes that disappeared 4 months later. The incidence of VABAM may be higher than reported. Routine brain MRI including DWI during VGB administration is recommended.