Introduction: We present a pediatric patient with three recurrent episodes of mild encephalopathy with reversible splenial lesion (MERS) caused by different infections over a 3-year period.

Case presentation: The patient was a 13-year 10-month-old boy with no abnormal findings in his birth or developmental history. He had three febrile seizures and frequent febrile delirium. (At first onset) At age 13, he developed delirium after fever and was diagnosed with influenza virus type B. Blood examinations revealed hyponatremia, and brain magnetic resonance imaging（MRI）revealed a lesion with reduced diffusion in the cerebral corpus callosum and periventricular white matter of the lateral ventricles, leading to a diagnosis of MERS type 2. Intravenous methylprednisolone (IVMP) was administered, as the patient had persistent abnormal behavior. The abnormal signals disappeared on the fifth day. (At second onset) At the age of 16 years and 5 months, he presented with fever and cough and was diagnosed with mycoplasma infection. Myoclonus-like involuntary movements of the right upper extremity were observed immediately after the onset of fever. On the second day, brain MRI showed a reduced diffusion region (type 2) at the same site as the first onset. IVMP was administered, but the involuntary movements of the right upper limb continued thereafter. On the 12th day, a second IVMP was performed, and the neurological symptoms resolved. (At the third onset) At the age of 16 years and 8 months, he presented with fever and was diagnosed with influenza virus type A. On the second day, he began to have involuntary movements of the right upper extremity. After admission, myoclonus-like seizures were observed in the right medial thigh and right face. On the second day, brain MRI revealed a reduced diffusion region in the cerebral corpus callosum (type 1), and IVMP was administered.

Conclusion: According to Japanese guidelines for the treatment of acute encephalopathy in children, aggressive therapeutic intervention is not required for MERS. However, because this patient presented with a variety of neurological symptoms, we administered medication, including IVMP, at the onset of the three episodes. Genetic background, such as the myelin regulatory factor（ MYRF ）gene abnormality, was considered one of the causes. These symptoms may repeat in the future and should be carefully monitored.

The patient was a 15-year-old boy. The patient initially had chills, and after 13 days, headache and fever appeared. On the 15th day of onset, right eyelid swelling and diplopia occurred, and he was diagnosed as periocular cellulitis at another hospital. After taking antibacterial medication, the patient did not improve. Head MRI revealed sinusitis and a left-sided subdural abscess. Antimicrobial therapy, steroid therapy, and immunoglobulin therapy were started, but the patient developed paralysis of the right lower extremity and was transferred to our hospital on the 20th day of onset. At the time of transfer, right upper and lower extremity motor paralysis, myoclonic seizures of the right lower extremity, disorientation, and tonic-clonic convulsions were observed. As the subdural abscess was not encapsulated and drainage of the abscess was difficult, only sinus drainage was performed. Propionibacterium acnes was detected in the sinuses. Brain MRI showed encephalitis in the left frontal lobe, and multidisciplinary treatment, including antibacterial therapy and steroid pulse therapy, was performed. Later, the abscess enlarged and formed a capsule over the entire subdural region of the left cerebral hemisphere; thus, neuroendoscopic drainage was performed on the 44th day of onset. Postoperatively, the patient's associated symptoms improved. The patient was discharged from the hospital without neurological symptoms on the 80th day of onset after continued administration of antimicrobial agents. Two and a half years later he had no recurrence and was without neurological sequelae, including higher functional impairment. Neuroendoscopy (soft speculum) can provide effective drainage and may contribute to prognosis.

As a result of the outbreak caused by the Omicron SARS-CoV-2 variant of coronavirus disease 2019 (COVID-19) in Japan,the number of pediatric patients has increased,and neurological complications have been reported. In this report,we describe two cases of COVID-19-related acute encephalopathy.

(Case presentation) Case 1: A 4-year-old boy with delayed motor development. He was diagnosed as acute encephalopathy with biphasic seizures and late reduced diffusion. The patient was treated with intravenous methylprednisolone (IVMP) and thyrotropin-releasing hormone (TRH). The patient was left with severe mental retardation and higher functional disability. Case 2: A 5-year-old girl with a history of febrile seizures. She presented with convulsive seizures and prolonged disturbance of consciousness. Cerebrospinal fluid (CSF) interleukin-6 was elevated at 364 pg/mL. She was diagnosed as febrile seizure and was treated with remdesivir,but her consciousness became prolonged and diffusion-weighted brain magnetic resonance imaging (MRI) showed hyperintensity in the left frontal lobe. The patient was diagnosed as unclassifiable acute encephalopathy. IVMP was administered with no apparent neurological sequelae. Based on cytokine analysis,we hypothesized that immunological mechanisms,such as hypercytokinemia,increased permeability of the blood-brain barrier,and vascular endothelial damage may cause COVID-19-related central nervous system complications.

A 56-year-old man, diagnosed with juvenile Alzheimer's disease by his primary care physician, presented with worsening symptoms after initiation of acetylcholinesterase inhibitor therapy. Head magnetic resonance imaging（MRI）revealed a unilateral limbic hyperintensity associated with a contrast effect. Cerebrospinal fluid analysis revealed no abnormality except for positive results for anti-leucine-rich glioma-inactivated 1 protein（LGI1）antibodies, which were also detected in the serum. Therefore, the patient was definitively diagnosed with anti-LGI1 antibody-positive limbic encephalitis. He responded to immunotherapy and successfully returned to social life. The patient did not show any faciobrachial dystonic seizure during the course of the disease and was conclusively diagnosed with this condition based on minor findings detected on head MRI. A high index of clinical suspicion is extremely important for accurate and early diagnosis of this disease based on imaging studies to avoid missed diagnosis of a treatable neurological condition.

The novel coronavirus disease 2019（ COVID-19 ）has undergone multiple mutations, and the current dominant strain is the highly infectious omicron mutant strain. The number of pediatric cases have increased, and more cases are displaying convulsions, impaired consciousness, encephalitis, and encephalopathy. Some severe cases may even have sequelae. We present three pediatric COVID-19 cases with acute encephalopathy. Similar to influenza encephalopathy, acute pediatric COVID-19 encephalopathy can display varied clinical presentations, severity, and prognoses.