近日，美国亚利桑那大学医学院Molly Wilson-Murphy团队研究了美国儿童流感相关急性坏死性脑病的流行病学。2025年7月30日出版的《美国医学会杂志》发表了这项成果。

急性坏死性脑病（ANE）是一种罕见但严重的神经系统疾病，其流行病学和治疗数据仍然有限。在2024-2025年美国流感季节，大型儿科中心的临床医生报告说，与流感相关的ANE儿童数量增加，促使了这项全国性调查。

为了了解美国儿童诊断为流感相关ANE的临床表现、干预措施和结果，研究组进行了一项多中心病例系列研究，对诊断为ANE的儿童进行纵向随访。通过学术协会、公共卫生机构以及直接联系76个美国学术中心的儿科专家发出了病例呼吁，要求在2023年10月1日至2025年5月30日期间提供病例。纳入标准为急性脑病，伴有急性丘脑损伤的放射学证据和21岁或以下个体流感感染的实验室证实。

暴露因素为流感相关的ANE。主要结局为呈现症状、疫苗接种史、实验室和遗传结果、干预措施和临床预后，包括改良Rankin量表评分(0分：无症状；1-2：轻度残疾；3-5：中度至重度残疾；6：死亡)、住院时间和功能预后。

在提交的58例病例中，41例(23例女性；年龄中位数为5岁[IQR， 2-8])，来自23家美国医院符合纳入标准。31例（76%）无明显病史；5例（12%）为医学并发症。临床表现为发热38例（93%），脑病41例（100%），癫痫发作28例（68%）。39例（95%）为甲型流感（14例为A/H1pdm/2009, 7例为A/H3N2, 18例无亚型），2例为乙型流感。实验室偏差包括肝酶升高（78%）、血小板减少（63%）和脑脊液蛋白升高（63%）。在32例（78%）进行基因检测的患者中，15例（47%）具有与ANE风险潜在相关的遗传风险等位基因，其中11例（34%）具有RANBP2变异。

在38名有疫苗接种史的患者中，只有6名（16%）接受了适龄季节性流感疫苗接种。大多数患者接受多种免疫调节治疗，包括甲基强的松龙（95%）、静脉注射免疫球蛋白（66%）、托珠单抗（51%）、血浆置换（32%）、阿那那单抗（5%）和鞘内注射甲基强的松龙（5%）。重症监护病房和住院时间的中位数分别为11天（IQR, 4-19）和22天（IQR, 7-36）。11名患者（27%）在症状发作后中位3天（IQR, 2-4）死亡，主要死于脑疝（91%）。在随访90天的27名幸存者中，63%至少有中度残疾（修正Rankin量表评分≥3）。

研究结果表明，在美国最近两个流感季节的流感相关ANE儿童系列病例中，这种情况与该队列中主要是年轻和以前健康的儿童的高发病率和死亡率有关。研究结果强调了预防、早期识别、强化治疗和标准化管理方案的必要性。

附：英文原文

Title: Influenza-Associated Acute Necrotizing Encephalopathy in US Children

Author: Influenza-Associated Acute Necrotizing Encephalopathy (IA-ANE) Working Group, Andrew Silverman, Rachel Walsh, Jonathan D. Santoro, Katherine Thomas, Elizabeth Ballinger, Kristen S. Fisher, Ajay X. Thomas, Brian Appavu, Michael C. Kruer, Derek Neilson, Jasmine Knoll, April N. Sharp, Hannah E. Edelman, Scott Otallah, Alexandra Morgan, Aniela Grzezulkowska, John Nguyen, Lekha M. Rao, Shaina M. Hecht, Laura Catalano, Hunter Daigle, Catherine Kronfol, Jessica Wharton, David Adams, Adam Z. Kalawi, Michael Kung, Janetta L. Arellano, Lauren Smith, Devorah Segal, Kristina Feja, Eileen Broomall, Anuj Jayakar, Sandra R. Arnold, Hanna Retallack, Craig A. Press, Grace Gombolay, Madeleine H. McLaughlin, Varun Kannan, Kavita Thakkar, Tasmia Rezwan, Erin Hulfish, Dalia Eid, Jennifer Meylor, Diane Peng, Ryan Hurtado, Taylor Nickerson, Iris Mandell, Abigail U. Carbonell, Mallory Kerner-Rossi, Divya Jayaraman, Mallory Davis, Rosemary Olivero, Neel Shah, Christina M. Osborne, Bo Zhang, Christopher Cortina, Adrienne G. Randolph, Suchitra Rao, Thomas LaRocca, Keith P. Van Haren, Molly Wilson-Murphy

Issue&Volume: 2025-07-30

Abstract:

Importance  Acute necrotizing encephalopathy (ANE) is a rare, but severe, neurologic condition for which epidemiologic and management data remain limited. During the 2024-2025 US influenza season, clinicians at large pediatric centers anecdotally reported an increased number of children with influenza-associated ANE, prompting this national investigation.

Objective  To understand the clinical presentation, interventions, and outcomes among US children diagnosed with influenza-associated ANE.

Design, Setting, and Participants  This study was a multicenter case series of children diagnosed with ANE with longitudinal follow-up. A call for cases was issued via academic societies, public health agencies, and by directly contacting pediatric specialists at 76 US academic centers, requesting cases between October 1, 2023, and May 30, 2025. Inclusion criteria required acute encephalopathy with radiologic evidence of acute thalamic injury and laboratory confirmation of influenza infection in individuals aged 21 years or younger.

Exposure  Influenza-associated ANE.

Main Outcomes and Measures  Presenting symptoms, vaccination history, laboratory and genetic findings, interventions, and clinical outcomes, including modified Rankin Scale score (0: no symptoms; 1-2: mild disability; 3-5: moderate to severe disability; 6: death), length of stay, and functional outcomes.

Results  Of 58 submitted cases, 41 cases (23 females; median age, 5 years [IQR, 2-8]) from 23 US hospitals met inclusion criteria. Thirty-one cases (76%) had no significant medical history; 5 (12%) were medically complex. Clinical presentation included fever in 38 patients (93%), encephalopathy in 41 (100%), and seizures in 28 (68%). Thirty-nine patients (95%) had influenza A (14 with A/H1pdm/2009, 7 with A/H3N2, and 18 with no subtype) and 2 had influenza B. Laboratory deviations included elevated liver enzymes (78%), thrombocytopenia (63%), and elevated cerebrospinal fluid protein (63%). Among 32 patients (78%) with genetic testing, 15 (47%) had genetic risk alleles potentially related to risk of ANE including 11 (34%) with RANBP2 variants. Among 38 patients with available vaccination history, only 6 (16%) had received age-appropriate seasonal influenza vaccination. Most patients received multiple immunomodulatory treatments, including methylprednisolone (95%), intravenous immunoglobulin (66%), tocilizumab (51%), plasmapheresis (32%), anakinra (5%), and intrathecal methylprednisolone (5%). Median intensive care unit and hospital lengths of stay were 11 days (IQR, 4-19) and 22 days (IQR, 7-36), respectively. Eleven patients (27%) died a median of 3 days (IQR, 2-4) from symptom onset, primarily from cerebral herniation (91%). Among the 27 survivors with 90-day follow-up, 63% had at least moderate disability (modified Rankin Scale score ≥3).

Conclusions and Relevance  In this case series of children with influenza-associated ANE from the 2 most recent influenza seasons in the US, the condition was associated with high morbidity and mortality in this cohort of predominantly young and previously healthy children. The findings emphasize the need for prevention, early recognition, intensive treatment, and standardized management protocols.

DOI: 10.1001/jama.2025.11534

Source: https://jamanetwork.com/journals/jama/fullarticle/2836871