Balcerac Alexander, Marois Clémence, Sterlin Delphine, Rohaut Benjamin, Demeret Sophie, Weiss Nicolas, Le Guennec Loic
AP-HP.Sorbonne Université, Faculté de Médecine, Sorbonne Université, Hôpital de la Pitié-Salpêtrière, 47-83 Boulevard de l'Hôpital, 75013, Paris, France.
Médecine Intensive Réanimation à Orientation Neurologique, Département de Neurologie, Hôpital de la Pitié-Salpêtrière, AP-HP.Sorbonne Université, Assistance Publique-Hôpitaux de Paris, 47-83 Boulevard de l'Hôpital, 75013, Paris, France.
Ann Intensive Care. 2025 Apr 30;15(1):60. doi: 10.1186/s13613-025-01475-7.
Central nervous system autoimmune diseases (CNS-AD) such as autoimmune encephalitis and myelitis are severe conditions, often requiring ICU admission. Early diagnosis is crucial but difficult, as initial steps facing sub-acute neurological disorders try to exclude non-immune causes such as stroke or infections through MRI and multiplex PCR assays. Current acute-phase autoimmune identifiers are lacking, with definitive diagnosis hinging on delayed tests like antibody detection or intrathecal immunoglobulin synthesis (ISI) identification via iso-electric focalization (IEF). This study evaluates surrogate markers, such as the IgG quotient (QIgG), IgG index, and Reiber's formula, which are rapidly obtainable, to quickly predict ISI in the ICU setting, aiming to expedite treatment initiation.
We screened all neuro-ICU admissions from 2008 to 2022 in our center, including patients who underwent a lumbar puncture (LP) and were tested for ISI via IEF. We excluded those lacking concomitant CSF/serum albumin and IgG data. Patients were categorized by final diagnosis as "CNS-AD" or "other", and whether ISI was present. We calculated QIgG, IgG index, and Reiber's formula, comparing their performance to IEF for sensitivity (Se) and specificity (Sp).
ISI was detected in 35% of patients (93/266). In the "CNS-AD" group, 54% were ISI-positive, while 21% of patients in the "Other" group also showed ISI. Among the three indexes, only the IgG index showed strong specificity (95%) but moderate sensitivity (56%). QIgG and Reiber's formula had similar sensitivity (67% and 66%) but lower specificity (41% for both). Multivariable analysis identified age < 50 years (OR 2.5 [95% CI 1.3-4.7]) and an IgG index > 0.7 (OR 14.2 [95% CI 6.6-32.0]) as factors independently associated with ISI positivity. Using the Youden index and likelihood ratio, we recalibrated thresholds to improve performance. A "grey zone" was defined for the IgG index (0.67-0.80), below which ISI was unlikely and above which it was considered probable.
While the IgG index's low sensitivity limits its standalone diagnostic use, its high specificity makes this index a good one when positive, to weigh in the decision-making process to treat or not a patient with suspected CNS-AD, while awaiting IEF results, which can take days or even weeks in some centers.
自身免疫性脑炎和脊髓炎等中枢神经系统自身免疫性疾病（CNS-AD）病情严重，常需入住重症监护病房（ICU）。早期诊断至关重要但颇具难度，因为面对亚急性神经系统疾病时，最初会通过磁共振成像（MRI）和多重聚合酶链反应（PCR）检测来排除诸如中风或感染等非免疫性病因。目前缺乏急性期自身免疫性标志物，确诊依赖于诸如抗体检测或通过等电聚焦（IEF）进行鞘内免疫球蛋白合成（ISI）鉴定等延迟检测。本研究评估了可快速获取的替代标志物，如IgG商（QIgG）、IgG指数和赖伯公式，旨在快速预测ICU环境中的ISI，以加快治疗启动。
我们筛选了2008年至2022年在本中心入住神经ICU的所有患者，包括接受腰椎穿刺（LP）并通过IEF检测ISI的患者。我们排除了缺乏脑脊液/血清白蛋白和IgG数据的患者。根据最终诊断将患者分为“CNS-AD”或“其他”，以及是否存在ISI。我们计算了QIgG、IgG指数和赖伯公式，并将它们与IEF在敏感性（Se）和特异性（Sp）方面的表现进行比较。
35%的患者（93/266）检测到ISI。在“CNS-AD”组中，54%为ISI阳性，而“其他”组中21%的患者也显示ISI阳性。在这三个指标中，只有IgG指数显示出高特异性（95%）但中等敏感性（56%）。QIgG和赖伯公式具有相似的敏感性（分别为67%和66%）但较低的特异性（均为41%）。多变量分析确定年龄<50岁（比值比[OR]2.5[95%置信区间（CI）1.3 - 4.7]）和IgG指数>0.7（OR 14.2[95%CI 6.6 - 32.0]）是与ISI阳性独立相关的因素。使用约登指数和似然比，我们重新校准了阈值以提高性能。为IgG指数定义了一个“灰色区域”（0.67 - 0.80），低于该区域ISI不太可能存在，高于该区域则认为可能存在。
虽然IgG指数的低敏感性限制了其单独用于诊断，但它的高特异性使其在呈阳性时成为一个很好的指标，可在等待IEF结果（在某些中心可能需要数天甚至数周）时，在决定是否治疗疑似CNS-AD患者的决策过程中加以权衡。
