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Purpose Forced normalization (FN) indicates psychotic episodes associated with seizure remission and disappearance of epileptiform activity on EEG. FN is likely to occur when frequent seizures are abruptly terminated by anti-epileptic drugs (AEDs) or epilepsy surgery. Methods We describe an atypical case of a patient with FN induced by lacosamide (LCM). Results A 23-year-old female patient with Lennox-Gastaut syndrome (LGS) was administered AEDs for LGS and hospitalised with weight loss and abnormal behaviour. Her condition fulfilled the FN criteria, which was considered to be induced by LCM. After a reduction in LCM dose, her abnormal behaviour and appetite improved. During LCM use, the patient developed no seizures, and the high amplitude diffuse sharp and slow wave complexes that were frequently observed before LCM disappeared on EEG. The LCM dose was tapered to 150 mg per day, and she became calmer with socially appropriate behaviours, although a few mild focal seizures relapsed. Conclusion LCM was effective for treating LGS in this patient and induced FN. Initially, it was difficult to recognise FN in cases of psychiatric disorders, especially in patients with intellectual disability. Patients with FN induced by LCM are rare, and only four patients have been previously reported who were treated by antipsychotic drug for psychosis.

Introduction Metachromatic leukodystrophy (MLD) refers to leukodystrophy caused by the accumulation of sulfatide from arylsulfatase A (ARSA) gene mutations. Sulfatide also accumulates in various organs, including the peripheral nerves, kidney, and gallbladder. Proliferative changes in the gallbladder have been reported in several patients, while gallbladder cancer is reported in only two adult MLD cases. We report what is likely the first pediatric case of MLD with gallbladder cancer. Case report The patient was a 5-year-old girl diagnosed with MLD using head magnetic resonance imaging and detecting a homozygous mutation of c.302G>A (p.Gly101Asp) in ARSA. Abdominal bloating was observed at the age of 4 years; CT revealed a giant tumor in the gallbladder and massive ascites. Cholecystectomy was performed and pathological examination revealed adenocarcinoma. Measurement of serum sulfatide revealed increased levels compared to the average healthy range. Discussion Rapidly increased ascites and large polyps which are reported as risk factors for cancer were characteristic in our MLD case. When such lesions are detected, they should be removed immediately because of the possibility of cancer, even in a pediatric patient.

Background A report presenting five heterozygous de novo variants in VAMP2 in unrelated individuals with a neurodevelopmental disorder characterized by axial hypotonia, intellectual disability, and autistic features was first published in April 4, 2019. Case report We report the case of a male child with VAMP2 variant who was delivered at 38 weeks and 4 days without neonatal asphyxia. At 4 months of age he showed hypotonia and no visual pursuit and fixation. He presented with infantile spasms at 6 months, and electroencephalography (EEG) showed hypsarrhythmia. His infantile spasms completely disappeared by adrenocorticotropic hormone therapy, but his EEG findings continued to show high voltage slow-waves with multi-focal spikes. At 2 years of age he was non-verbal, had an absence of purposeful hand movements, and no visual fixation. He had somnolence tendency in the daytime. Biochemical and extensive genetic examinations were unrevealed. Magnetic resonance imaging showed slight brain atrophy. At 2 years and 7 months of age, he suffered from myoclonic seizures of the eyelid and tongue, which propagated to unilateral fingers, and sometimes to the bilateral legs. At 8 years of age hyperkinetic movement occurred. At age 13, whole-exome sequence identified a heterozygous missense variant, NM_014232.2:c.199G>C,[p.(Ala67Pro)] in exon 3 of VAMP2 which was a de novo non-synonymous variant. Conclusion This is the first case report of VAMP2 variant in Japan. Hypotonia at early infancy, poor visual fixation, and absence of purposeful hand movements may be indicative of the diagnosis for VAMP2 variant.

Mutations in the mitochondrial tRNAMet gene have been reported in only five patients to date, all of whom presented with muscle weakness and exercise intolerance as signs of myopathy. We herein report the case of a 12-year-old girl with focal epilepsy since the age of eight years. At age 11, the patient developed sudden visual disturbances and headaches accompanied by recurrent, stroke-like episodes with lactic acidosis (pH 7.279, lactic acid 11.6 mmol/L). The patient frequently developed a delirious state, exhibited regression of intellectual ability. Brain magnetic resonance imaging revealed high-intensity signals on T2-weighted images of the left occipital lobe. Mitochondrial gene analysis revealed a heteroplasmic m.4450G > A mutation in the mitochondrial tRNAMet. The heteroplasmic rate of the m.4450G > A mutation in blood, skin, urinary sediment, hair, saliva, and nail samples were 20, 38, 59, 41, 27, and 35%, respectively. The patient’s fibroblast showed an approximately 53% reduction in the oxygen consumption rate, compared to a control, and decreased complex I and IV activities. Stroke-like episodes, lactic acidosis, encephalopathy with brain magnetic resonance imaging findings, and declined mitochondrial function were consistent with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome. To our knowledge, the findings associated with this first patient with MELAS syndrome harboring the m.4450G > A mutation in mitochondrial tRNAMet expand the phenotypic spectrum of tRNAMet gene.

Introduction Levetiracetam has a high tolerability and is effective against various seizure types and epilepsy syndromes. However, no study has specifically evaluated the efficacy of levetiracetam in children with refractory epilepsy based on magnetic resonance imaging (MRI) findings and the presence of intellectual disability (ID). Methods We retrospectively evaluated levetiracetam efficacy and safety in 49 pediatric patients who met the following inclusion criteria: (1) diagnosis of refractory epilepsy with first-line antiepileptic (AED) treatment ⩾2 years, (2) younger than 20 years old, and (3) received oral levetiracetam treatment for ⩾6 months. We assessed the relationships of these outcomes with MRI findings and ID status. Results Eighteen (37%) patients achieved a ⩾50% reduction in seizure frequency, and the majority (78%) had no remarkable side effects. Twenty-two (45%) patients had previously been treated with more than seven antiepileptic drugs prior to levetiracetam. Among 18 patients who achieved a ⩾50% reduction in seizure frequency, 13 and 5 had negative and positive MRI findings, and 9 and 9 had and did not have ID, respectively. Conclusions Our findings suggest that even for intractable pediatric cases with symptomatic etiology (i.e., MRI lesion and ID), levetiracetam has favorable efficacy for refractory epilepsy with tolerable adverse effects.