【要旨】単純ヘルペスウイルス（herpes simplex virus：HSV）は、ヒトに多様な疾患を引き起こす。HSV 感染症に対しては、いくつかの抗ヘルペスウイルス剤が開発されているが、単純ヘルペス脳炎では、死亡と高度後遺症を含めた転帰不良率は 33〜53％と高く、社会復帰率も半数でしかない。本稿では、単純ヘルペス脳炎発症の分子基盤の一端に関して、われわれの知見に基づき概説する。

【要旨】次世代シーケンサーを活用したショットガンメタゲノム解析とはサンプル内に含まれる細菌や真菌、ウイルス、原虫などの病原体ゲノムをわずか1 つのアッセイで網羅的に検出できる革新的なゲノム診断技術である。わずかなサンプル量から病原体ゲノムを検出できるため、生検脳や脳脊髄液を対象にした本解析は、脳炎や髄膜炎の感染症スクリーニングとして役立つ。一方で、高コストであり、偽陽性や偽陰性の問題もある。

【要旨】進行性多巣性白質脳症（Progressive Multifocal Leukoencephalopathy：PML）は、ポリオーマウイルス科の JC ウイルス（JCV）に起因する脱髄疾患である。多くのヒトでは、アーキタイプ（原型）の JCV が終生にわたって無症候性に持続感染および潜伏感染している。そして、Ｔ細胞系の免疫が低下した患者等においては、プロトタイプ（変異型）の JCV が出現し、大脳白質等のオリゴデンドロサイトにおいて増殖することで PML を生じることがある。本稿では、「PML の臨床と検査」を中心として、JCV の性状、PML の発生動向、診断基準、ならびに具体的な検査等について概説する。

【要旨】子どもは当初 SARS-CoV-2 に感染することが少なかったが、オミクロン株に置き換わってから感染例が激増した。ただ子どもは大人（特に高齢者）にくらべて重症化することがきわめて少なく、その機序としては自然免疫応答の強さや抗感冒コロナウイルス免疫の交差反応が想定されている。重症化率は低くても感染例が激増したことを受けて重症例・死亡例がみられるようになり、特に国内では急性脳症の併発が危惧されている。またコロナ禍における社会の変化や子どもの感染予防対策が過度に行われることにより、子どもの心の発達を妨げられ心の健康を蝕まれていることに留意すべきである。

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.

【要旨】56 歳男性、前医で若年性アルツハイマー型認知症と診断され、アセチルコリンエステラーゼ阻害薬を開始したところ症状が悪化したため当院のもの忘れ外来を受診した。頭部 MRI で片側ではあるが辺縁系の信号上昇を認め、造影効果も伴っていた。髄液検査で異常はなかったが、血清と髄液中の抗 leucine-rich glioma-inactivated 1 protein（LGI1）抗体が陽性であることが判明し、抗 LGI1 抗体陽性辺縁系脳炎と診断した。免疫療法は奏功し社会生活へ復帰した。本症例では経過中に faciobrachial dystonic seizure は一度も認めず、頭部 MRI の軽微な所見から本疾患を疑って診断にいたることができた。治療可能な神経疾患を見落とさないという点から、画像検査を契機として本疾患を早期から鑑別にあげることが重要である。

【要旨】Corona virus infectious disease, emerged in 2019（COVID-19）は、流行の主体が感染性の高いオミクロン変異株に置き換わり小児の感染者数が増加し、けいれん、意識障害、脳炎・脳症例も増加し、重症化する症例や後遺症を残す症例も報告されている。われわれが経験した小児 COVID-19 の出血性ショック脳症症候群や、片側けいれん・片麻痺・てんかん症候群を含む3 症例の急性脳症を提示する。小児 COVID-19 の急性脳症はインフルエンザ脳症と同様、さまざまな臨床病型・重症度、そして予後をとりうる。