Severe Disturbance Of Consciousness Research Articles

Levodopa-resistant parkinsonism developing after ventriculoperitoneal shunting for obstructive hydrocephalus and improving after endoscopic third ventriculostomy, with specific consideration of brainstem morphology: illustrative case.

Parkinsonism has been reported in patients with obstructive hydrocephalus (OH) following ventriculoperitoneal shunting (VPS). While levodopa works well, some cases are drug resistant. A few case series have reported that endoscopic third ventriculostomy (ETV) is beneficial, though its mechanism remains unclear. The use of a pathophysiology-reflected marker can aid in the diagnosis and treatment strategy. The authors report a case of parkinsonism due to OH after VPS that improved after ETV in a patient taking levodopa, which was subsequently discontinued. A 52-year-old man who had undergone VPS for OH caused by aqueductal stenosis with a tectal tumor presented with severe consciousness disturbance due to acute hydrocephalus and levodopa-refractory parkinsonism after multiple episodes of shunt malfunction. Magnetic resonance imaging showed an elevation of the floor of the third ventricle. ETV was performed to stabilize the pressure imbalance across the stenosis, and his parkinsonism symptoms improved after long-term rehabilitation, resulting in levodopa discontinuation. His pontomesencephalic angle, the angle between the anterior surface of the midbrain and upper surface of the pons in the midline of the sagittal plane, was significantly decreased. The focus in such cases should be on the essence of the pathophysiology for improving the symptoms rather than on easy-to-understand indicators such as ventricle size. https://thejns.org/doi/10.3171/CASE2429.

Coil embolization for ruptured distal anterior cerebral artery aneurysm at the supracallosal portion: Two case reports

Background: Distal anterior cerebral artery (ACA) aneurysms occur more frequently in the genu portion and much less frequently in the supracallosal portion (A4–A5). This report describes two cases of ruptured cerebral aneurysms occurring at the supracallosal portion successfully treated with coil embolization. Case Description: Case 1 involved a 61-year-old female with sudden-onset headache and vomiting attributed to subarachnoid hemorrhage (SAH). Digital subtraction angiography (DSA) revealed a bihemispheric ACA and aneurysm in the supracallosal portion. Coil embolization was performed, and the patient was discharged without neurological deficit. Case 2 involved a 35-year-old man with severe headache and disturbance of consciousness caused by SAH. DSA showed an aneurysm in A4 of the accessory ACA, and coil embolization was performed. After rehabilitation, he was discharged with a modified Rankin scale score of 2. Conclusion: Coil embolization for a ruptured aneurysm at the supracallosal portion can yield good results if the patient is appropriately selected.

Actinobacillus ureae may be a critical pathogen in patients with predispositions: A case report and review of the literature.

Actinobacillus ureae (A. ureae) is an unusual commensal of human respiratory flora, rarely causing human infection. The predisposing factors, identification, clinical features, and antibiotic therapy of A. ureae are seldomly reported. Herein, we present a case of 64-year-old man affected by A. ureae pneumonia after intracranial surgery. A 64-year-old male was admitted with vomiting, drowsiness, and a severe disturbance of consciousness and was later diagnosed with cerebral hemorrhage by computed tomography images. After a craniocerebral surgery, the patient suffered from intractable pneumonia, experiencing treatment failure with multiple anti-bacterial agents. Sputum culture yield pure colonies of A. ureae, confirmed by matrix-assisted laser desorption/ionization time of flight and 16S rRNA gene sequencing. Minocycline (100 mg p.o. per 12 hours) with a course of 15 days was administrated for this patient. The respiratory symptoms, presenting as intermittent coughing with purulent and yellowish sputum, were gone. A 3-month follow-up examination showed a complete resolution of radiological findings. Clinically, the actual incidence of A. ureae pneumonia may be higher than that we generally recognized, and clinicians should consider A. ureae as a possible etiologic agent in patients with predispositions. Currently, A. ureae may be susceptible to penicillin, ampicillin, and third-generation cephalosporins. Other antibacterial agents, such as tetracycline, amoxicillin/clavulanic acid, and aminoglycosides also respond well and can be a choice in the treatment of A. ureae infections.

Association of glycemic variability with death and severe consciousness disturbance among critically ill patients with cerebrovascular disease: analysis of the MIMIC-IV database

BackgroundThe association of glycemic variability with severe consciousness disturbance and in-hospital all-cause mortality in critically ill patients with cerebrovascular disease (CVD) remains unclear, This study aimed to investigate the association of glycemic variability with cognitive impairment and in-hospital death.MethodWe extracted all blood glucose measurements of patients diagnosed with CVD from the Medical Information Mart for Intensive Care IV (MIMIC-IV). Glycemic variability was defined as the coefficient of variation (CV), which was determined using the ratio of standard deviation and the mean blood glucose levels. Cox hazard regression models were applied to analyze the link between glycemic variability and outcomes. We also analyzed non-linear relationship between outcome indicators and glycemic variability using restricted cubic spline curves.ResultsThe present study included 2967 patients diagnosed with cerebral infarction and 1842 patients diagnosed with non-traumatic cerebral hemorrhage. Log-transformed CV was significantly related to cognitive impairment and in-hospital mortality, as determined by Cox regression. Increasing log-transformed CV was approximately linearly with the risk of cognitive impairment and in-hospital mortality.ConclusionHigh glycemic variability was found to be an independent risk factor for severe cognitive decline and in-hospital mortality in critically ill patients with CVD. Our study indicated that enhancing stability of glycemic variability may reduced adverse outcomes in patients with severe CVD.

Triglyceride glucose index is a significant predictor of severe disturbance of consciousness and all-cause mortality in critical cerebrovascular disease patients

ObjectiveThe association of the triglyceride-glucose (TyG) index with severe consciousness disturbance and in-hospital mortality in patients with cerebrovascular disease in the intensive care unit (ICU) is unclear. This study aimed to investigate the TyG index’s predictive ability on the severity of impaired consciousness and in-hospital mortality in patients with cerebrovascular disease in the ICU.MethodPatients diagnosed with non-traumatic cerebral hemorrhage and cerebral infarction were extracted from the MIMIC-IV database and analyzed as two cohorts. The association between the TyG index and the severity of patients’ impairment of consciousness and in-hospital mortality was analyzed using logistic regression models. Using restricted cubic spline curves, we analyzed potential nonlinear relationships between TyG indices and outcome indicators. receiver operating characteristic (ROC) curves were utilized to evaluate the predictive ability of the TyG index for outcome indicators.ResultThe study’s last two cohorts comprised 537 patients with traumatic cerebral hemorrhage and 872 patients with cerebral infarction. TyG index was a significant predictor of the severity of impaired consciousness and in-hospital mortality in patients with cerebrovascular disease, as determined by logistic regression. The risk of severe consciousness impairment and in-hospital mortality increased roughly linearly with increasing TyG index.ConclusionThe TyG index was found to be a significant predictor for severe impairment of consciousness and in-hospital death in patients with cerebrovascular disease in the ICU, and it provides some predictive value for the severity of consciousness disturbances and in-hospital mortality in cerebrovascular disease patients.

Survival of community-acquired Bacillus cereus sepsis with venous sinus thrombosis in an immunocompetent adult man – a case report and literature review

BackgroundBacillus cereus infections in immunocompetent patients are uncommon and mainly observed in fragile patients. It can cause lethal infections with multiple organ dysfunction syndrome (MODS). However, a patient presenting as venous sinus thrombosis and survival without sequela has not been reported.Case presentationA 20-year-old previously healthy male developed gastroenteritis after a meal, followed by fever, convulsions, and severe disturbance of consciousness. The patient had significant leukocytosis with a mildly elevated D-dimer, creatinine level, and respiratory failure. The CT(computed tomography) revealed fatal brain edema and subarachnoid hemorrhage. Previous blood culture in a local hospital revealed B. cereus, which was confirmed by mNGS(metagenomic next-generation sequencing) using blood and urine in our hospital. Accordingly, B. cereus sepsis with MODS were considered. Later, cerebral venous sinus thrombosis was proved. After anti-infection (linezolid 0.6 g, Q12h; and meropenem 1.0 g, Q8h), anti-coagulant (enoxaparin 6000U, Q12h), and other symptomatic treatments, the patient recovered completely without sequela at the 6-month follow-up.ConclusionsThis case suggests that in immunocompetent adults, there is still a risk of infection with B. cereus, causing severe MODS. Special attention should be paid to venous sinus thrombosis and subarachnoid hemorrhage in such cases, while, anti-coagulant is essential therapy.

レジオネラ肺炎を契機に発症したAcute–on–chronic liver failureの救命例(A case of acute–on–chronic liver failure caused by Legionella pneumonia)

レジオネラ肺炎は，多臓器不全を合併し致死的な経過をたどることがある。今回，ACLFに伴う肝性脳症を合併するも，人工肝補助療法を導入し，救命し得た症例を経験したので報告する。症例は50歳の男性で，高度意識障害と多臓器不全のため近隣病院から転院搬送された。搬入時より意識レベルはJCS III–300であり，血液検査でアンモニアが高値であった。肝性脳症と診断し，直ちにon–line HDFによる人工肝補助療法を開始した。第2病日に尿中レジオネラ抗原が陽性となったことから，レジオネラ肺炎と診断し，それに伴って多臓器不全を発症した状態であると判断した。抗生剤については，メロペネム，レボフロキサシン，アジスロマイシンを投与した。凝固障害に対しては，適宜輸血を実施した。合計3回のon–line HDFとCHDFを交互に実施し，緩徐に意識レベルの改善が得られ，第5病日には意識清明となった。第8病日にICUを退出し，第20病日に転院した。ACLFは，最近定義された新しい疾患概念であり，代償性あるいは非代償性肝硬変に増悪因子が加わって，高度の肝機能異常を呈する病態である。治療については症候に対する対症療法が中心であり，本症例では人工肝補助療法を導入したことで覚醒が得られ，救命に寄与したと考えられた。 Legionella pneumonia may be complicated by multiple organ failure and may result in death. We herein report a case of hepatic encephalopathy associated with acute–on–chronic liver failure, which was successfully rescued by artificial liver support therapy. A 50–year–old man was transferred from a nearby hospital due to severe disturbance of consciousness and multiple organ failure. His level of consciousness was Japan coma scale III–300, and a blood test revealed a high level of ammonia. Hepatic encephalopathy was diagnosed as the cause of consciousness disturbance, and artificial liver support therapy with on–line hemodiafiltration was started immediately. On Day 2, Legionella pneumonia was diagnosed because urinary Legionella antigen was positive. For antibiotics, meropenem, levofloxacin, and azithromycin were administered. Blood transfusion was performed as needed for coagulopathy. The patient’s level of consciousness gradually improved, and he became lucid on Day 5. He was discharged from the intensive care unit on Day 8 and transferred to another hospital on Day 20. We believe that the rapid introduction of artificial liver support therapy enabled the patient to regain consciousness. レジオネラ肺炎は，多臓器不全を合併することで，致死的な経過をたどることがある。アルコール多飲歴が感染のリスクであるため，大酒家であればその発症に注意を払う必要がある。一方，大酒家は肝硬変に罹患していることが多く，acute–on–chronic liver failure（ACLF）を発症することで，慢性肝不全が急激に進行する可能性がある。今回，レジオネラ肺炎の感染を契機にACLFを発症し肝性脳症に陥るも，on–line hemodiafiltration（HDF）による人工肝補助療法を導入することで，覚醒が得られた症例を経験したので報告する。 本論文に倫理委員会の承諾は必要がない。また本論文は個人情報保護法に基づいて匿名化がなされ，患者またはその家族より論文の出版に関する同意を得ている。 患 者：50歳の男性 主 訴：なし（高度意識障害） 既往歴：急性腹膜炎で手術歴あり，C型肝炎ウイルス（hepatitis C virus: HCV）感染後 sustained virological response，アルコール依存症（精神科病院に入院歴あるも通院は自己中断） 内服歴：常用薬なし。健康食品，サプリメントや漢方薬の使用なし 家族歴：肝疾患の家族歴なし 生活歴：温泉や循環式風呂の入浴なし。加湿器の使用なし。飲酒はアルコール度数9%の缶チューハイ2,500mL/day。喫煙は20本/dayを30年間。アレルギー歴なし。生肉の摂取なし。職業は土木建築業。両肩から両前腕にかけて刺青あり 現病歴：搬送数日前から車上生活を送っていた。搬送当日，河川敷に本人の車両が放置されており，警察官が周囲を捜索したところ，車両から約400m離れた土手で倒れている本人を発見し救急要請された。全身に明らかな外傷は認めず，車内には飲酒後と思われる空き缶が散在していた。過量服薬や違法薬物の使用の痕跡はなかった。直近二次病院に搬送されたが，Japan Coma Scale（JCS）III–300の高度意識障害と黄疸があり，採血では肝機能障害，腎機能障害，凝固障害，電解質異常を認めた。体幹部の単純computed tomography（CT）では両側スリガラス陰影と脂肪肝を疑わせる肝臓の斑状低吸収域を認めたが，明らかな胸腹水は認めなかった。前医では対応困難であり，多臓器不全に対する集中治療目的に当院の救命救急センターに緊急転院搬送となった。 入院時現症：身長168cm，体重70.7kg，body mass index 25.0kg/m2，意識レベル Glasgow Coma Scale（GCS）E1V1M1，体温36.9度，血圧135/81mmHg，脈拍110/min・整，呼吸数30/min，SpO2 98%（酸素マスク5L/min）であった。瞳孔は左右同大5mmで対光反射は両側迅速，眼球結膜に黄染を認めた。胸部聴診では，心音は整で雑音はなく，両側胸部でcoarse cracklesを聴取した。腹部は膨満，軟で腹部正中に手術痕あり，右季肋部に肝臓を三横指触知し，波動は認めず，クモ状血管腫や女性化乳房も認めなかった。両側下腿に軽度の圧痕性浮腫を認めた。 入院時検査所見：当院で再検した血液検査（Table 1）では，貧血，凝固障害，肝機能障害，腎機能障害，電解質異常と多臓器不全を呈していた。新型コロナウイルス感染症の迅速抗原検査およびpolymerase chain reaction（PCR）検査は陰性であった。HCV ribonucleic acid（RNA）は陰性であった。また，尿中薬物検査キットもすべて陰性であった。頭部CTでは意識障害を来しうる脳出血や腫瘤性病変は認めなかった。体幹部単純CT（Fig. 1）では，両側上葉優位に浸潤影や網状影を認め，下葉に淡い濃度上昇を伴う陰影を認めたが，明らかな胸水貯留は指摘できなかった。肝形態は保たれており，肝臓周囲には腹水は認めず，胆嚢の浮腫性変化も認めなかった。入院時の血液検査結果では，FIB–4スコアは20.9点で，C型肝硬変の判別式は20点であった。 CT scans of the patient. A: Day 1, B: Day 7, C: Day 15 The abnormal chest opacity gradually improved. B showed ascites accumulation (white arrow), but C showed improvement. 入院後経過（Fig. 2）：病歴や所見からは元々アルコール性慢性肝硬変が背景にあり，何らかの要因で急性増悪し，ACLFおよび肝性脳症を来したものと考えた。肝性脳症については，犬山分類 grade Vであり，右内頸静脈からバスキュラーアクセスを確保し，直ちにon–line HDF（透析膜：FIX250E；ニプロ，血流量200mL/min，透析液流量500mL/min，補充液流量5,000mL/hour）を開始した。On–line HDFに伴い，血清カリウムとリンの低下が懸念され，適宜補正を行った。貧血と凝固障害に対しては，輸血を行い，ビタミンK製剤の投与を行った。消化管出血の懸念があったため，経鼻胃管は挿入せずに，経肛門的にラクツロースの注腸を開始した。分岐鎖アミノ酸製剤の投与については，窒素負荷につながり，肝性脳症を助長する可能性があると判断したため実施しなかった。On–line HDF終了後は，continuous hemodiafiltration（透析膜：セプザイリス；バクスター，血流量100mL/min，補充液流量400mL/min，排液量800mL/min，透析液流量400mL/min，以下CHDF）での血液浄化を開始した。敗血症の可能性は否定できず，各種培養を採取した後に，メロペネム（meropenem: MEPM）の投与を開始した。呼吸不全については，マスクでの酸素投与のみで酸素化が維持可能であり，努力呼吸も認めなかったことから，気管挿管や人工呼吸器管理は見送った。肺炎像の鑑別目的に，第2病日に実施した尿中レジオネラ抗原（リボテスト；旭化成ファーマ）が陽性となったため，レジオネラ肺炎と確定診断し，病態としてレジオネラ肺炎が契機となりACLFを発症したものと考えた。また，レボフロキサシン（levofloxacin: LVFX）の静注を開始した。培養検査については，当院ではbuffered charcoal yeast extract（BCYE）培地を常備しておらず，ヒメネス染色も外部発注の検査となること，尿中抗原陽性であれば，感染症法の四類感染症の定義を満たすことから実施しなかった。喀痰loop–mediated isothermal amplification（LAMP）法については外注であったが提出し，結果，良好な喀痰が得られなかったことと，LVFXを投与後に検体を採取した影響のためか陰性であった。一方で，第2病日のアンモニアが280μg/dLと増悪していたため，分岐鎖アミノ酸製剤は引き続き投与せず，2回目のon–line HDFを導入した。On–line HDF後の採血では，アンモニアが130μg/dLと改善しており，意識レベルも改善を認めた。第3病日に，重症のレジオネラ肺炎と判断し，LVFXに加えて，アジスロマイシン（azithromycin: AZM）の静注を開始し，AZMについては合計5日間投与した。同日の採血では，アンモニアは改善傾向であったが，依然として意識障害が残存していたため，3回目のon–line HDFを実施した。その後は乏尿が続いていたため，腎代替療法としてCHDFによる除水を継続した。3回目のon–line HDF施行後より，徐々に意識レベルは改善し，第4病日には軽度の見当識障害を認めるのみとなった。黄疸については，皮膚掻痒感の訴えに対し軟膏塗布での対症療法，経過観察とした。第6病日より食事（蛋白20g制限食）とリファキシミンの内服を開始した。第7病日に体幹部CTを再検査したところ，肺炎像については改善傾向を認め，新たに腹水が貯留していた。同日，自尿が増加傾向であったため，CHDFから離脱した。全身状態として経過が順調であったことから，第8病日にICUを退室した。また，入院時に採取した培養検査がすべて陰性であったことを確認し，MEPMの投与は終了した。第12病日にLVFXは内服へ移行し，静注と内服で合計21日間の抗生剤治療を予定した。一般床に転棟後は，羽ばたき振戦や異常行動を認めることなく経過した。第15病日に体幹部CTを再検し，肺炎像と腹水が消退傾向であることを確認した。第20病日に肝不全や黄疸に対する治療継続目的，およびリハビリテーション継続目的に，独歩で近隣病院に転院した。 Clinical course of the patient. i.v: intravenous drip, p.o: per os 今回，ACLFを合併し，肝性脳症により昏睡状態に陥るも，on–line HDFを用いた人工肝補助療法を導入することで，覚醒が得られたレジオネラ肺炎の1例を経験した。我々が渉猟し得た限りでは，本邦で類似症例の報告はなく，本症例はレジオネラ肺炎が契機となってACLFを合併し，on–line HDFを用いることで救命し得た初の報告である。 レジオネラ菌（Legionella pneumophilla）は，1976年の米国在郷軍人会で発生した重症肺炎の原因菌として，1977年に初めて同定された好気性ブドウ糖非発酵グラム陰性桿菌である1。世界中の土壌中や環境水中に存在し，埃やエアロゾルとして吸入することで感染が成立する。市中肺炎のみならず，院内肺炎の起因菌としても重要である。細胞内寄生菌のため，細胞内へ移行し効果を発揮するβ–ラクタム系の抗菌薬は無効であり，早期の治療介入のためには鑑別すべき疾患として挙げることが必要である。ところが，確定診断のためにはヒメネス染色やBCYE培地での細菌培養，喀痰LAMP法といった，施設によっては外部発注での検査が必要となることが課題であった。近年ではその報告件数は増加傾向となっており2，要因として，1999年に感染症法の四類感染症に指定されたことや，2003年に尿中抗原検査が保険適応となったことが挙げられる。 重症度という点に着目すると，レジオネラ肺炎はしばしば多臓器不全を合併し，致死的な経過をたどることがある2。高柳らの報告によれば，死亡は65例中6例で，死因として敗血症性ショックや腎不全，播種性血管内凝固，多臓器不全の併発によるものであった2。とくに，多臓器不全を合併した3例中2例が死亡しており，レジオネラ肺炎に多臓器不全を合併した場合の致死率は極めて高いことが推察される。また，レジオネラ肺炎の発症リスクとして，高齢，男性，免疫抑制状態，慢性肺疾患，アルコール多飲歴，悪性腫瘍，鉄過剰症，tumor necrosis factor–α（TNF–α）治療歴，および喫煙が挙げられている3。本症例では，アルコール多飲歴やアルコール依存症の既往歴を認めていたことから，確定診断はされていないものの，基礎疾患としてアルコール性慢性肝硬変の存在が示唆され，発症リスクが高かったと推測された。また，肝硬変による免疫不全状態と考えれば，重症化しやすい素因も併せ持っていたと推測された。すなわち，アルコール多飲歴，肝硬変，レジオネラ肺炎の三者が，相互に悪影響を及ぼしたため，重症化に至ったと考えられた。 そのような背景のなかで，本症例ではレジオネラ肺炎が契機となってACLFを発症したと考えた。そもそも肝不全とは，肝細胞の減少ないし機能低下によって生体の恒常性が維持できなくなることであり，発症から肝不全に至るまでの期間で，急性，遅発性，慢性に分類されている4。急性肝不全とは「肝炎の発症から8週間以内に，高度の肝機能障害に基づいて昏睡II度以上の昏睡を来し，プロトロンビン時間が40%以下を示すもの」と定義される4。一方で，ACLFとは，「Child–Pughスコアが5～9点の代償性ないし非代償性肝硬変に，アルコール多飲，感染症，消化管出血，原疾患増悪などの増悪因子が加わって，28日以内に高度の肝機能異常に基づいて，プロトロンビン時間INRが1.5以上ないし同活性が40%以下で，血清総ビリルビン値が5.0mg/dL以上を示す症例」と厚生労働省の研究班により2018年に定義された5。急性肝不全とACLFは，正常肝あるいは肝予備能が正常の慢性肝疾患が背景にあるかどうか，という点で差別化された。診断に至るまでの因果関係として，急性肝不全が先行し，全身状態が悪化した後にレジオネラ肺炎を二次的に合併した，という可能性についても考慮されたが，レジオネラ肺炎が多臓器不全を発症しうる2という点を根拠に，本症例では，元々アルコール多飲に伴った肝硬変が存在し，レジオネラ肺炎を契機にACLFを発症したものと考えた。 ACLFの治療については，肝移植を除けば特異的かつ決定的なものはない6。原因に対する治療や，症候に対する対症療法が基本となる7。アルコール性慢性肝炎に準じたステロイドの投与については考慮したが，本症例では実施しなかった。肺野の異常陰影が，間質性肺炎の急性増悪であった場合，なおのことステロイドの投与が考慮されたが，レジオネラ肺炎の診断に至ったためにその必要性が低下し，人工肝補助療法での治療が奏功しない場合に，その実施を検討する方針としていたためである。血漿交換（plasma exchange: PE）についても，まずはon–line HDFで肝性脳症治療を進め，覚醒が得られない場合に実施を検討する方針としていた。幸い，on–line HDFとCHDFによる治療が奏功したため，血漿交換の導入は不要であった。肝移植については，現実的な問題として多臓器不全を呈しており，全身麻酔に耐えうるかが不明であったこと，背景にアルコール依存症があり，断酒もできていないことから，適応はないと判断した。 急性肝不全の内科的治療における両輪は，蛋白合成能（とくに血液凝固因子）の補助と解毒能の代替である8。前者については，新鮮凍結血漿（fresh frozen plasma: FFP）の輸血やアルブミン投与，ビタミンK製剤の補充を行うことが基本となる。本症例では，プロトロンビン時間40%を目標に適宜FFPを投与した。後者については，解毒すべき物質，すなわち肝性脳症の原因物質の排除が必要となる。本邦では，欧米と比較して肝移植のドナーが見つかりにくいという背景から人工肝補助療法が発展してきた9。肝性脳症の原因物質の代表の一つにアンモニアがあり10，アンモニアは肝性脳症患者の主たる死亡原因である脳浮腫および脳ヘルニアを惹起する可能性が示唆されている11。すなわち，人工肝補助療法の最大の目的は，肝性脳症から覚醒させ，意識障害を改善させることにある。アンモニアは分子量17g/moLと低分子であるため，小分子除去に効率の良い血液透析（hemodialysis: HD）が有効と考えられるが，実際にはHDでの肝性脳症の覚醒率は40%程度である12。これは，アンモニア以外に中分子の肝性脳症物質が関与しているためと考えられている（中分子仮説）が，具体的な物質の同定までは至っていない13。ほか，PE，血液濾過（hemofiltration: HF）での覚醒率は37.5%，78%程度である12。単独での実施は効果に乏しく，両者の利点を併せ持ったHDFが有効と考えられる。とくに，中央配管から供給される純水を透析液と置換液として使用し，前希釈法によるon–line HDFが効率的かつ経済的であるという報告が挙がっている14。本邦では，PEとHDFによるコンビネーション法が主流とされる15が，本症例では，まずon–line HDFを実施し，効果が得られない場合にPEを併用する方針としていた。結果，PEは回避することができ，on–line HDF単独でも良好な覚醒が得られ，脳ヘルニアに至ることなく経過した。覚醒率が高いということは，ICU入室期間の短縮にもつながる。合併症や続発症の低減などによる要素が，救命に寄与したと考えられた。本症例を通して，急性肝不全による肝性脳症のみならず，ACLFによる肝性脳症に対しても，on–line HDFによる人工肝補助療法が効果的であることが示唆された。 人工肝補助療法におけるon–line HDFの注意すべき点の一つとして，透析液が腎不全用であることが挙げられる16。すなわち，カリウム，リンが透析液中に不足しており，重炭酸が過剰に含まれている。アンモニアと同様に，カリウムとリンも小分子であるため，on–line HDFの開始に伴い急激に低下する可能性があり，注意が必要である。本症例では，HDF開始前と開始後約2時間が経過した時点，終了後の3ポイントで血液検査を実施し，カリウムとリンの値を逐一確認し，適宜補正を行った。また，薬剤や栄養についても影響を受けるため注意が必要と考えられる。本症例では，とくに抗生剤治療において，濃度依存性のLVFXと腎機能に応じて調整不要のAZMが治療の主軸であったため，on–line HDFの影響を考慮することなく治療を進めることが可能であった。 レジオネラ肺炎を契機としてアルコール性慢性肝硬変を背景にACLFを合併し，肝性脳症に陥った症例を経験した。肝性脳症に対して，on–line HDFによる人工肝補助療法を導入したことで覚醒が得られ，救命し得たと考えられた。 本論文における利益相反はない。

Clinical features of autoimmune encephalitis secondary to epidemic encephalitis B in 5 children

To study the clinical features of children with autoimmune encephalitis (AE) secondary to epidemic encephalitis B (EEB). A retrospective analysis was performed on the medical data of five children with EEB with "bipolar course" who were treated in Children's Hospital Affiliated to Zhengzhou University from January 2020 to June 2022. Among the five children, there were three boys and two girls, with a median age of onset of 7 years (range 3 years 9 months to 12 years) and a median time of 32 (range 25-37) days from the onset of EEB to the appearance of AE symptoms. The main symptoms in the AE stage included dyskinesia (5/5), low-grade fever (4/5), mental and behavioral disorders (4/5), convulsion (2/5), severe disturbance of consciousness (2/5), and limb weakness (1/5). Compared with the results of cranial MRI in the acute phase of EEB, the lesions were enlarged in 3 children and unchanged in 2 children showed on cranial MRI in the AE stage. In the AE stage, four children were positive for anti-N-methyl-D-aspartate receptor antibody (one was also positive for anti-γ-aminobutyric acid type B receptor antibody), and one was negative for all AE antibodies. All five children in the AE stage responded to immunotherapy and were followed up for 3 months, among whom one almost recovered and four still had neurological dysfunction. EEB can induce AE, with anti-N-methyl-D-aspartate receptor encephalitis as the most common disease. The symptoms in the AE stage are similar to those of classical anti-N-methyl-D-aspartate receptor encephalitis. Immunotherapy is effective for children with AE secondary to EEB, and the prognosis might be related to neurological dysfunction in the acute phase of EEB.

Hepatocyte-specific damage in acute toxicity of sodium ferrous citrate: Presentation of a human autopsy case and experimental results in mice.

Acute iron overload is known to exert deleterious effects in the liver, but detailed pathology has yet to be documented. Here, we report pathological findings in an autopsy case of acute iron toxicity and validation of the findings in mouse experiments. In a 39-year-old woman who intentionally ingested a large amount of sodium ferrous citrate (equivalent to 7.5g of iron), severe disturbance of consciousness and fulminant hepatic failure rapidly developed. Liver failure was refractory to treatment and the patient died on Day 13. Autopsy revealed almost complete loss of hepatocytes, while bile ducts were spared. To examine the detailed pathologic processes induced by excessive iron, mice were orally administered equivalent doses of ferrous citrate. Plasma aminotransferase levels markedly increased after 6h, which was preceded by increased plasma iron levels. Hepatocytes were selectively damaged, with more prominent damage in the periportal area. Phosphorylated c-Jun was detected in hepatocyte nuclei after 3h, which was followed by the appearance of γ-H2AX expression. Hepatocyte injury in mice was associated with the expression of Myc and p53 after 12 and 24h, respectively. Even at lethal doses, the bile ducts were morphologically intact and fully viable. Our findings indicate that acute iron overload induces hepatocyte-specific liver injury, most likely through hydroxyl radical-mediated DNA damage and subsequent stress responses.

Effect of early mobilization in patients with stroke and severe disturbance of consciousness: Retrospective study

ObjectivesThis study aimed to investigate the effectiveness and safety of early mobilization with a physiatrist and registered therapist Operating rehabilitation (PROr) for patients with stroke and severe disturbance of consciousness (DoC). Materials and methodsWe retrospectively screened records from patients with stroke admitted to our hospital from January 2015 to June 2021. Eligible patients with severe DoC were classified into two groups: patients who received standard rehabilitation (control group) and patients who received PROr (PROr group). We studied longitudinal change in the level of consciousness using the Japan Coma Scale (JCS) during hospital stay and compared in-hospital mortality, the incidence of respiratory complication, and modified Rankin Scale of discharge between the two groups. ResultsAmong the 2191 patients screened for inclusion, 16 patients were included in the PROr group, and 12 patients were included in the control group. Early mobilization was more promoted in the PROr group compared to the control group, but there were no significant differences in in-hospital mortality, the incidence of respiratory complication, or modified Rankin Scale at discharge between the two groups. In patients who survived during their hospital stay, JCS scores 2 weeks after the onset of stroke and JCS scores at discharge significantly improved from the start of rehabilitation in the PROr group, but not in the control group. ConclusionsEarly mobilization provided with the PROr program appears to be a safe treatment and may contribute to the improvement of consciousness level for patients with acute stroke and severe DoC.

Complex poisoning mainly with benzyl alcohol complicated by paralytic ileus: a case report

BackgroundBenzyl alcohol is used as stripping agent in paints and other applications, and benzyl alcohol poisoning is indicated by symptoms, such as impaired consciousness, respiratory depression, hypotension, metabolic acidosis, and renal dysfunction.Case presentationA 27-year-old Asian man was transported to a hospital for severe disturbance of consciousness following exposure to a paint stripper containing benzyl alcohol, ethylene glycol, and hydrogen peroxide, which he was using to repaint a bridge. The patient was treated under sedation for benzyl alcohol poisoning. On day 3 of hospitalization, his abdominal computed tomography scan revealed a paralytic ileus, so he was transferred to our hospital. The combined toxicity from multiple substances, mainly benzyl alcohol, was thought to be a contributing factor for the paralytic ileus. Upon arrival, the patient also had chemical burns, hypernatremia, and elevated myogenic enzyme levels. His urinary hippuric acid level was high (14.9 g/L) upon admission to the previous hospital. We treated the patient with artificial respiration management, while avoiding high-density oxygen, and with gastrointestinal decompression by gastric tube implantation; laxatives were also administered. The paralytic ileus improved on the 4th day, the tube was removed on the 6th day, and the patient was discharged on the 11th day of hospitalization. No apparent complications were observed at discharge.ConclusionsTo the best of our knowledge, this is the first case report of paralytic ileus caused by benzyl alcohol, although multiple factors may have influenced the symptoms. After exposure to benzyl alcohol by inhalation and dermal absorption, the patient developed impaired consciousness, metabolic acidosis, and paralytic ileus, and the presence of elevated urinary hippuric acid led to a definitive diagnosis.

Coronavirus disease 2019‐associated encephalopathy: Characteristic brainstem and bilateral temporal lobe involvement

AbstractBackgroundAs COVID‐19 has become a worldwide pandemic, various neurological manifestations associated with the virus have been discovered. Apart from cerebrovascular disorders, central nervous system inflammation associated with COVID‐19 has also been reported.Case PresentationHere we report a rare case of COVID‐19 encephalopathy in Japan that specifically involved the brainstem and bilateral temporal lobes. In addition to the moderate respiratory damage, the patient developed generalized seizures followed by severe disturbance of consciousness. MRI examinations demonstrated characteristic involvement of the brainstem and bilateral temporal lobes. Pulsed steroid treatment effectively resolved the abnormal MRI findings.ConclusionsThe mechanisms of neuronal damage in COVID‐19 remain undetermined, but pathogenesis of this case should be considered an autoimmune mechanism rather than direct viral damage to the central nervous system in COVID‐19.

Aetiology and frequency of coma in Emergency department of the primary healthcare centre

Background/Aim: Coma is the most severe disturbance of consciousness from which the patient cannot wake up and in which there is no verbal and motor response or opening of the eyes. The aim of the research was to establish the frequency of occurrence of coma and the aetiology of coma in the Banja Luka Emergency Department (ED). Also, the goal was to analyse the accuracy of the referral diagnosis and potential factors that can help the doctor in making a correct diagnosis. Methods: A retrospective cross-sectional study was conducted. In the ED database, in the period from January to September 2022, all patients diagnosed with coma have been found. The gender and age of the patient, vital parameters, performed diagnostic methods and therapy were recorded. The referral diagnosis, the department to which the patient was referred, as well as the final diagnosis determined in hospital conditions were recorded. Results: In the period from January to September 2022 there were 95 patients who were diagnosed with coma. The average age of the patients was 67.76 ± 16.56 years, there were 56 (58.9 %) men and 39 (41.1 %) women. Of that number, 41 (43.2 %) patients were diagnosed with hypoglycaemic coma and those patients were treated in the field. Out of 54 patients, 32 (59.3 %) patients had a confirmed referral diagnosis, while 22 (40.7 %) patients had another diagnosis established at the hospital. All patients with suspected intracranial bleeding or stroke were correctly diagnosed and adequately referred, while all patients with a confirmed diagnosis of sepsis and shock were incorrectly referred (ch2 = 30.563, p < 0.001). Conclusion: The most frequent were coma caused by hypoglycaemia and coma caused by brain ischaemia and non-traumatic bleeding, which were adequately recognised and treated and/or referred. Coma caused by sepsis and shock of different aetiology was not recognised as such and was referred to a neurologist, where precious time was wasted. In order to reduce errors in the field, it is necessary to pay more attention to the anamnestic data on diseases and perform a somatic and neurological examination adequately.

A Fiber Dissection Study of the Anterior Commissure: Correlations with Diffusion Spectrum Imaging Tractography and Clinical Relevance in Gliomas.

The anterior commissure, which connects bilateral temporal lobes and olfactive areas, remains elusive in many aspects of its structure and functional role. To comparatively describe anatomical details of the anterior commissure using cadaveric fiber dissection (FD) and diffusion spectrum imaging (DSI) thus refining our knowledge of the tract and exploring its clinical relevance in glioma migration. Twelve normal postmortem hemispheres were treated with Klingler's method and subjected to FD with medial, inferior, and lateral approaches. The FD findings were correlated with DSI tractography results. To illustrate the clinical relevance, two patients with recurrent temporal high-grade glioma are described. Our FD and DSI tractography of the anterior commissure disclosed a new anatomical paradigm. The FD confirmed that the anterior limb (absent sometimes and variable) and the lateral/temporal extension include the rostral portion and caudal portion, respectively, of the anterior commissure fibers. The shape of the lateral/temporal extension predominantly resembles an 'H'. The DSI tractography findings corresponded to these FD results. According to the FD, the Virchow-Robin space is continuous with the subarachnoid space and very close to the anterior commissure. The two clinical cases presented severe disturbances of consciousness and behavior despite good local tumor control. Subsequent magnetic resonance images showed new lesions infiltrating the contralateral temporal lobes. FD combined with DSI provided anatomical details facilitating a better understanding of the anterior commissure. Glioma migration routes to the contralateral temporal lobe included the anterior commissure, Virchow-Robin space, and subarachnoid space and were clinically relevant.

Hepatic Encephalopathy Mimicking Creutzfeldt-Jakob Disease on Laboratory, Physiological, and Imaging Evaluations

Patient: Female, 84-year-old Final Diagnosis: Hepatic encephalopathy Symptoms: Cognitive impairment Medication:— Clinical Procedure: — Specialty: Neurology Objective: Unusual clinical course Background:Creutzfeldt-Jakob disease (CJD) is an irreversible, neurodegenerative, prion disease presenting with cognitive, behavioral, and motor dysfunction. The clinical presentations or laboratory findings of treatable autoimmune and metabolic processes may mimic those of CJD. Hepatic encephalopathy (HE) is a complication of severe hepatic failure that is characterized by neuropsychiatric manifestations. A case of HE whose laboratory, physiological, and imaging results were similar to that of Creutzfeldt-Jakob disease (CJD) in the process of treatment for HE is presented.Case Report:An 84-year-old woman with hepatic encephalopathy (HE) was admitted to our hospital because of acute consciousness disturbance. She had chronic hepatitis type C, liver cirrhosis, and hepatocellular carcinoma, and had had an episode of HE once. Her severe consciousness disturbance did not improve after treatment for concurrent hyperammonemia, unlike in her previous episode. Diffusion-weighted brain magnetic resonance imaging (MRI) showed widespread hyperintensity of the whole cortex. Her electroencephalogram showed periodic sharp wave complexes (PSWCs). Both total t-tau and 14-3-3 proteins were detected in her cerebrospinal fluid. According to these clinical data, CJD was highly suspected. However, the consciousness disturbance was alleviated by the tenth day of admission, and her general condition was markedly improved, which supported the initial diagnosis of HE.Conclusions:The present results suggest that treatable disorders, such as HE, should be considered before making a final diagnosis of a fatal disease such as CJD, since the spectrum of diseases that CJD mimics is vast. We should also aggressively treat patients with severe conditions from which recovery is possible.

Immediate and Short-term Outcome of Acute Disseminated Encephalomyelitis (ADEM) after corticosteroid therapy

Background : Acute disseminated encephalomyelitis (ADEM) is an acute demyelinating disorder of the central nervous system (CNS) occurring predominantly but not exclusively in children. The presence of severe disturbance of consciousness together with multifocal neurological symptoms and signs especially in a child under 10 years of age; favours a diagnosis of ADEM. Neuroimaging is essential investigation for establishing the diagnosis of ADEM. High-dose steroid treatment frequently results in a dramatic clinical improvement.
 Objective: This study aimed to describe our experience with Acute Disseminated Encephalomyelitis (ADEM) focusing on the clinical features, neuroimaging, and outcome after treatment with high-dose steroid.
 Method: This retrospective observational study was conducted in children who were admitted as inpatients in Paediatric Neurosciences Department of Dhaka Shishu Hospital (DSH) with the diagnosis of ADEM during the period of 2017- 2019. All patients got high dose IV methylprednisolone for 5 days followed by 2 weeks tapering dose of steroid. Outcome was observed on the 7th day of treatment and 6 months after discharge from hospital.
 Result: A total of 16 patients who were diagnosed as ADEM were included in this study. Twelve children (75%) had a recent upper respiratory tract illness. Patients presented most often with motor deficits (88%) and secondly with altered consciousness (63% ) followed by seizure ( 50% ). MRI brain was the preferable neuroimaging which mostly (41.7%) showed multifocal symmetrical demyelination patch. On the 7th day of steroid treatment, significant improvement in motor function and level of consciousness occurred (p values were 0.001% and 0.014% respectively). After 6 months of discharge from hospital; no motor deficit, age-appropriate cognitive level and no seizure in 71%, 57% and 71% respectively.
 Conclusion: High dose corticosteroid treatment in ADEM is significantly effective in improvement of motor impairment and consciousness level on immediate follow up.
 Northern International Medical College Journal Vol.11 (2) Jan 2020: 468-470

Outcomes of elderly patients with organophosphate intoxication

This study analysed the clinical patterns and outcomes of elderly patients with organophosphate intoxication. A total of 71 elderly patients with organophosphate poisoning were seen between 2008 and 2017. Patients were stratified into two subgroups: survivors (n = 57) or nonsurvivors (n = 14). Chlorpyrifos accounted for 33.8% of the cases, followed by methamidophos (12.7%) and mevinphos (11.3%). Mood, adjustment and psychotic disorder were noted in 39.4%, 33.8% and 2.8% of patients, respectively. All patients were treated with atropine and pralidoxime therapies. Acute cholinergic crisis developed in all cases (100.0%). The complications included respiratory failure (52.1%), aspiration pneumonia (50.7%), acute kidney injury (43.7%), severe consciousness disturbance (25.4%), shock (14.1%) and seizures (4.2%). Some patients also developed intermediate syndrome (15.5%) and delayed neuropathy (4.2%). The nonsurvivors suffered higher rates of hypotension (P < 0.001), shock (P < 0.001) and kidney injury (P = 0.001) than survivors did. Kaplan–Meier analysis indicated that patients with shock suffered lower cumulative survival than did patients without shock (log-rank test, P < 0.001). In a multivariate-Cox-regression model, shock was a significant predictor of mortality after intoxication (odds ratio 18.182, 95% confidence interval 2.045–166.667, P = 0.009). The mortality rate was 19.7%. Acute cholinergic crisis, intermediate syndrome, and delayed neuropathy developed in 100.0%, 15.5%, and 4.2% of patients, respectively.

Electroencephalographic findings in Bickerstaff’s brainstem encephalitis: A possible reflection of the dysfunction of the ascending reticular activating system

ObjectivesBickerstaff’s brainstem encephalitis (BBE) is a rare post-infectious inflammatory disease, which causes impaired consciousness by the dysfunction of the ascending reticular activating system (ARAS). We aimed to clarify EEG changes possibly caused by the dysfunction of the ARAS in BBE. MethodsWe retrospectively investigated 15 EEGs from 5 patients with definite BBE (i.e., the positivity for serum IgG anti-GQ1b antibodies was mandatory for the diagnosis) admitted to our hospital from January 2014 through December 2019, particularly focusing on whether N1 and N2 sleep patterns were maintained. ResultsAll of the 10 EEGs recorded when patients had consciousness disturbance were abnormal. Stereotypical EEG changes correlating with their level of consciousness were identified: poorly organized posterior dominant rhythms with maintenance of sleep patterns in patients with mild consciousness disturbance (n = 5); predominant N1 and/or N2 sleep patterns even with external stimuli, including spindle coma pattern, in patients with moderate consciousness disturbance (“unarousable sleep-like” EEG) (n = 4); and generalized slow waves without N1 and N2 sleep patterns in patients with severe consciousness disturbance (n = 1). Among 5 patients, 3 (60%) had “unarousable sleep-like” EEG in their clinical course. ConclusionsPatients with BBE showed stereotypical EEG changes correlating with their level of consciousness, mostly with maintenance of N1 and N2 sleep patterns, and often exhibited characteristic “unarousable sleep-like” EEG. SignificanceThis study revealed characteristic EEG changes possibly caused by the dysfunction of the ARAS, which can be a diagnostic clue for BBE.

Clinical study on the cerebral infarction accompanied with septic disseminated intravascular coagulation.

Patients with disseminated intravascular coagulation (DIC) due to sepsis often develop cerebral infarction; but the frequency, mechanism of onset and prognosis have not been fully elucidated. We reported courses and characteristics of septic DIC cases hospitalized in our hospital in the present study. Patients with septic DIC who underwent brain imaging were selected. Vital signs, disorders of consciousness and blood test results at the time of onset were compared between cases that developed cerebral infarction (cerebral infarction group) and those that did not (non-infarction group).In cases of cerebral infarction, the site and the size of the infarct lesion were also described. In 27 septic DIC patients who underwent brain imaging, eight patients had cerebral infarction. Although the percentage of patients who survived in the cerebral infarction group (2/8, 25%) was lower than that in the non-infarction group (7/17, 37%), , no significant difference was observed as both group showed poor prognoses. Those two patients who survived in the cerebral infarction group had severe consciousness disturbance and poor functional prognosis. Although the body temperature was significantly lower and the blood pressure was higher in the cerebral infarction group, no significant difference was found in general blood tests, so we thought it would be necessary to look for other markers that could be indicators for the risk of cerebral infarction.In the cerebral infarction group, two cases had a single lesion, and six cases had multiple lesions. Of the latter, two cases had massive lesions with a diameter of 1.5cm or greater, four cases had only small lesions with a diameter of less than 1.5cm, and two cases had a mixture of both. Most of the patients had lesions in the vertebrobasilar artery, which suggested that the pathogenesis involves not only embolism due to microthrombi, but also vasculitis and intravascular inflammation. Cerebral infarction was observed highly frequently; eight out of 27 cases (29.6%) when brain imaging was undergone in septic DIC patients. The prognosis of patients with cerebral infarction was poor, but no difference from the non-infarction group was observed. In addition to embolism, the presence of inflammation is considered to be important for the onset. In order to predict the prognosis and determine a suitable treatment, it would be recommended to undergo brain imaging when patients with septic DIC have consciousness disturbance or elevated blood pressure, and do not have fever.

Clinical features of anti-myelin oligodendrocyte glycoprotein antibody-associated diseases in children with cortical encephalitis

Objective: To describe the clinical features of anti-myelin oligodendrocyte glycoprotein (MOG) antibody-positive cortical encephalitis in children. Methods: Patients who were hospitalized in Beijing Children's Hospital from June 2018 to October 2019, with positive MOG antibodies and phenotype of cortical encephalitis were retrospectively analyzed. Cell-based assays (CBAs) were used to test MOG antibodies. Results: Five patients had the phenotype of cortical encephalitis during follow-up, with 3 females and 2 males. The age of onset ranged from 8 years to 12 years and 1 month. At the last follow-up, 3 cases exhibited a monophasic course and 2 cases were with relapse and remission courses. Six out of 8 episodes which had the phenotype of cortical encephalitis presented with seizures, among which 3 episodes had status epilepticus. None had recurrent seizures during remission. Other symptoms included fever (7/8), headache and vomiting (4/8), somnolence (3/8) and hemiplegia (1/8). Unilateral cortical swelling was observed in cerebral magnetic resonance imaging (MRI) of all patients, without any hemorrhage and necrosis. White blood cell (WBC) counts of cerebrospinal fluid increased, ranging from8×10(6)/L to 186×10(6)/L. All patients recovered well after treatment with intravenous immunogloblin and glucocorticoid. Two patients had relapses during follow-up and were additionally treated with mycophenolate mofetil. Conclusions: Anti-MOG antibodies can induce cortical encephalitis. In clinical setting, fever, headache and seizures are common, however, severe consciousness disturbance and local neurological deficits are rare in these patients. Cerebral MRI shows unilateral cortical swelling without any hemorrhage and necrosis. Usually, immunotherapy works well. No patients exist repeated seizures in remission, but some patients may have relapses.