Lischer Mirko, Trendelenburg Marten, Yaldizli Özgür, Avramiotis Nikolaos S, Marti Grischa, Vital Anna
Division of Internal Medicine, University Hospital of Basel, Basel, Switzerland.
Division of Neurology, University Hospital of Basel, Basel, Switzerland.
Eur J Case Rep Intern Med. 2025 Aug 18;12(9):005705. doi: 10.12890/2025_005705. eCollection 2025.
Encephalitis is a potentially life-threatening condition with infectious or autoimmune aetiologies. Autoimmune encephalitis includes paraneoplastic variants associated with specific onconeural antibodies such as anti-Hu, frequently linked to malignancies. Herpes simplex virus type 1 (HSV-1) is the leading infectious cause in adults. Differentiating between these aetiologies can be challenging. We report the case of an 88-year-old woman admitted with confusion following a fall. Initial evaluation showed clinical signs consistent with encephalitis. During hospitalisation, a seizure was witnessed. Cerebrospinal fluid (CSF) analysis revealed mild pleocytosis, but no infectious agent was detected, and brain imaging revealed no significant abnormalities. After initial improvement under antiepileptic therapy, the patient experienced worsening cognitive dysfunction. Repeat CSF testing 4 weeks after initial symptom onset showed even milder pleocytosis but was positive for HSV-1 and magnetic resonance imaging showed bilateral hippocampal hyperintensities. Analysis of the first CSF sample retrospectively revealed high-titer anti-Hu antibodies. Positron emission tomography-computed tomography scan identified a hypermetabolic lung lesion and para-aortic lymph node, with biopsy confirming the diagnosis of small cell lung cancer. Immunosuppressive and oncologic treatment led to transient improvement, followed by progressive neurological deterioration. Supportive care was ultimately prioritized. This case underscores the diagnostic challenges of encephalitis, especially when autoimmune and infectious features overlap, and diagnostic findings are misleading. Detection of HSV-1 should not delay the investigation of alternative causes of encephalitis in the absence of typical HSV-related features. Early recognition of paraneoplastic encephalitis is critical, as neurologic symptoms may precede the diagnosis of underlying malignancy.
Onconeural antibodies, such as anti-Hu antibodies, are an under-recognized cause of encephalitis and should be specifically tested for when an autoimmune encephalitis is clinically suspected.Detection of anti-Hu antibodies mandates a comprehensive malignancy workup.A positive herpes simplex virus type 1 polymerase chain reaction in cerebrospinal fluid does not definitively confirm active infection and must always be interpreted in conjunction with the patient's clinical presentation.
脑炎是一种由感染性或自身免疫性病因引起的潜在危及生命的疾病。自身免疫性脑炎包括与特定肿瘤神经抗体（如抗Hu）相关的副肿瘤性变体，常与恶性肿瘤相关。1型单纯疱疹病毒（HSV-1）是成人脑炎的主要感染性病因。区分这些病因可能具有挑战性。我们报告了一例88岁女性患者，因跌倒后出现意识模糊入院。初步评估显示临床体征与脑炎相符。住院期间，观察到一次癫痫发作。脑脊液（CSF）分析显示轻度细胞增多，但未检测到感染病原体，脑部影像学检查未发现明显异常。在抗癫痫治疗后最初有所改善，但患者随后出现认知功能障碍恶化。初始症状出现4周后重复进行脑脊液检测，显示细胞增多更为轻微，但HSV-1呈阳性，磁共振成像显示双侧海马高信号。回顾性分析首次脑脊液样本发现高滴度抗Hu抗体。正电子发射断层扫描-计算机断层扫描（PET-CT）发现肺部高代谢病变和主动脉旁淋巴结，活检确诊为小细胞肺癌。免疫抑制和肿瘤治疗导致短暂改善，随后神经功能逐渐恶化。最终优先采取支持性护理。该病例强调了脑炎的诊断挑战，尤其是当自身免疫和感染特征重叠且诊断结果具有误导性时。在没有典型HSV相关特征的情况下，检测到HSV-1不应延迟对脑炎其他病因的调查。早期识别副肿瘤性脑炎至关重要，因为神经症状可能先于潜在恶性肿瘤的诊断出现。
肿瘤神经抗体（如抗Hu抗体）是一种未被充分认识的脑炎病因，当临床怀疑自身免疫性脑炎时应进行特异性检测。检测到抗Hu抗体需要进行全面的恶性肿瘤检查。脑脊液中1型单纯疱疹病毒聚合酶链反应阳性并不能明确证实存在活动性感染，必须始终结合患者的临床表现进行解读。
