Vlad Benjamin, Neidhart Stephan, Hilty Marc, Ziegler Mario, Jelcic Ilijas
Department of Neurology, University Hospital Zurich and University of Zurich, Zurich, Switzerland.
Neuroimmunology and Multiple Sclerosis Research Section, Department of Neurology, University Hospital Zurich and University of Zurich, Zurich, Switzerland.
Front Neurol. 2023 Mar 24;14:1135392. doi: 10.3389/fneur.2023.1135392. eCollection 2023.
Neurosarcodosis is one of the most frequent differential diagnoses of multiple sclerosis (MS) and requires central nervous system (CNS) biopsy to establish definite diagnosis according to the latest consensus diagnostic criteria. We here analyzed diagnostic values of basic cerebrospinal fluid (CSF) parameters to distinguish neurosarcoidosis from MS without CNS biopsy.
We retrospectively assessed clinical, radiological and laboratory data of 27 patients with neurosarcoidosis treated at our center and compared following CSF parameters with those of 138 patients with relapsing-remitting MS: CSF white cell count (WCC), CSF/serum albumin quotient (Q), intrathecal production of immunoglobulins including oligoclonal bands (OCB), MRZ reaction, defined as a polyspecific intrathecal production of IgG reactive against ≥2 of 3 the viruses measles (M), rubella (R), and zoster (Z) virus, and CSF lactate levels. Additional inflammatory biomarkers in serum and/or CSF such as neopterin, soluble interleukin-2 receptor (sIL-2R) and C-reactive protein (CRP) were assessed.
There was no significant difference in the frequency of CSF pleocytosis, but a CSF WCC > 30/μl was more frequent in patients with neurosarcoidosis. Compared to MS, patients with neurosarcoidosis showed more frequently an increased Q and CSF lactate levels as well as increased serum and CSF levels of sIL-2R, but a lower frequency of intrathecal IgG synthesis and positive MRZ reaction. Positive likelihood ratio (PLR) of single CSF parameters indicating neurosarcoidosis was highest, if (a) CSF WCC was >30/μl (PLR 7.2), (b) Q was >10 × 10 (PLR 66.4), (c) CSF-specific OCB were absent (PLR 11.5), (d) CSF lactate was elevated (PLR 23.0) or (e) sIL-2R was elevated (PLR>8.0). The combination of (a) one of three following basic CSF parameters, i.e., (a.1.) CSF WCC >30/ul, or (a.2.) Q >10 × 10, or (a.3.) absence of CSF-specific OCB, and (b) absence of positive MRZ reaction showed the best diagnostic accuracy (sensitivity and specificity each >92%; PLR 12.8 and NLR 0.08).
Combined evaluation of basic CSF parameters and MRZ reaction is powerful in differentiating neurosarcoidosis from MS, with moderate to severe pleocytosis and Q elevation and absence of intrathecal IgG synthesis as useful rule-in parameters and positive MRZ reaction as a rule-out parameter for neurosarcoidosis.
神经结节病是多发性硬化症（MS）最常见的鉴别诊断之一，根据最新的共识诊断标准，需要进行中枢神经系统（CNS）活检以确诊。我们在此分析了基本脑脊液（CSF）参数在不进行CNS活检的情况下区分神经结节病与MS的诊断价值。
我们回顾性评估了在我们中心接受治疗的27例神经结节病患者的临床、放射学和实验室数据，并将以下CSF参数与138例复发缓解型MS患者的参数进行了比较：CSF白细胞计数（WCC）、CSF/血清白蛋白商（Q）、鞘内免疫球蛋白产生（包括寡克隆带（OCB））、MRZ反应（定义为针对麻疹（M）、风疹（R）和带状疱疹（Z）病毒中的≥2种病毒产生多特异性鞘内IgG反应）以及CSF乳酸水平。还评估了血清和/或CSF中的其他炎症生物标志物，如新蝶呤、可溶性白细胞介素-2受体（sIL-2R）和C反应蛋白（CRP）。
CSF细胞增多的频率无显著差异，但神经结节病患者中CSF WCC>30/μl更为常见。与MS相比，神经结节病患者的Q和CSF乳酸水平升高以及血清和CSF中sIL-2R水平升高更为常见，但鞘内IgG合成频率和MRZ反应阳性率较低。单个CSF参数提示神经结节病的阳性似然比（PLR）最高的情况为：（a）CSF WCC>30/μl（PLR 7.2），（b）Q>10×10（PLR 66.4），（c）无CSF特异性OCB（PLR 11.5），（d）CSF乳酸升高（PLR 23.0）或（e）sIL-2R升高（PLR>8.0）。以下三个基本CSF参数中的一个，即（a.1.）CSF WCC>30/μl，或（a.2.）Q>10×10，或（a.3.）无CSF特异性OCB，与（b）无MRZ反应阳性相结合，显示出最佳的诊断准确性（敏感性和特异性均>92%；PLR 12.8和NLR 0.08）。
基本CSF参数和MRZ反应的联合评估在区分神经结节病与MS方面具有强大作用，中度至重度细胞增多、Q升高以及无鞘内IgG合成作为有用的纳入参数，而MRZ反应阳性作为神经结节病的排除参数。
