Brownlee Wallace J, Foster Michael A, Pontillo Giuseppe, Davagnanam Indran, Collorone Sara, Prados Ferran, Kanber Baris, Barkhof Frederik, Thompson Alan J, Toosy Ahmed T, Ciccarelli Olga
Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Institute of Neurology, London, United Kingdom.
NIHR University College London Hospitals Biomedical Research Centre, United Kingdom.
Neurology. 2025 Apr 8;104(7):e210274. doi: 10.1212/WNL.0000000000210274. Epub 2025 Mar 4.
The diagnosis of multiple sclerosis (MS) requires evidence of both dissemination in space (DIS) and time (DIT); oligoclonal bands (OCBs) in the CSF can substitute for DIT on MRI. We investigated whether DIT (or positive CSF) is necessary to make a diagnosis of MS in patients who fulfil a high number of DIS criteria.
We prospectively recruited patients with a first demyelinating event evaluated with brain and spinal cord MRI within 3 months of onset. The patients were followed up clinically and with MRI. We retrospectively applied DIS criteria requiring lesions in ≥2/4, ≥3/4, or 4/4 regions typically affected in MS (periventricular, cortical/juxtacortical, infratentorial, spinal cord) and ≥2/5, ≥3/5, ≥4/5, and 5/5 regions (including the optic nerve) to baseline assessments. We investigated the performance of each set of DIS criteria for a diagnosis of MS using the 2017 McDonald criteria, requiring both DIS (lesions in ≥2/4 regions) plus DIT on MRI (gadolinium-enhancing and nonenhancing lesions, new T2 lesions at follow-up) or CSF-specific OCBs, as the gold standard.
We included 244 patients (mean age 32.5 years, 154 [63%] female); 187 (77%) patients were diagnosed with MS using the 2017 McDonald criteria over a mean follow-up of 11.2 years. DIS alone, requiring lesions in ≥2/4, ≥3/4, or 4/4 regions, exhibited reducing sensitivity (84%, 58%, and 26%, respectively) and increasing specificity (91%, 98%, 100%) for an MS diagnosis. In 112 (46%) patients with optic nerve assessment with orbital MRI or visual evoked potentials, DIS in ≥2/5, ≥3/5, ≥4/5, or 5/5 regions also resulted in reducing sensitivity (96%, 83%, 61%, 30%) and increasing specificity (44%, 83%, 100%, 100%) for MS diagnosis. We propose a diagnostic algorithm for MS in patients with a first demyelinating event based on the number of DIS regions fulfilled.
In patients with a first demyelinating event, DIS in ≥4 regions typically affected in MS is highly specific, indicating an extremely low risk of false-positive results, and misdiagnosis. Using DIS in ≥4 regions would reduce the need for follow-up MRI or CSF examination in all patients with suspected MS, streamlining the diagnostic process. Limitations include an over-representation of patients with optic neuritis at onset, a low rate of CSF examination, and lack of optical coherence tomography data.
多发性硬化症（MS）的诊断需要具备空间播散（DIS）和时间播散（DIT）的证据；脑脊液中的寡克隆带（OCB）可替代MRI上的DIT。我们研究了在满足大量DIS标准的患者中，DIT（或脑脊液阳性）对于MS诊断是否必要。
我们前瞻性招募了首发脱髓鞘事件的患者，在发病3个月内进行脑和脊髓MRI评估。对患者进行临床和MRI随访。我们回顾性地将DIS标准应用于基线评估，这些标准要求在MS中典型受累的≥2/4、≥3/4或4/4个区域（脑室周围、皮质/皮质下、幕下、脊髓）以及≥2/5、≥3/5、≥4/5和5/5个区域（包括视神经）出现病变。我们使用2017年麦克唐纳标准（要求DIS（≥2/4个区域出现病变）加MRI上的DIT（钆增强和非增强病变，随访时出现新的T2病变）或脑脊液特异性OCB）作为金标准，研究每组DIS标准对MS诊断的性能。
我们纳入了244例患者（平均年龄32.5岁，154例[63%]为女性）；在平均11.2年的随访中，187例（77%）患者根据2017年麦克唐纳标准被诊断为MS。单独的DIS，要求在≥2/4、≥3/4或4/4个区域出现病变，对MS诊断的敏感性分别降低（84%、58%和26%），特异性增加（91%、98%、100%）。在112例（46%）通过眼眶MRI或视觉诱发电位进行视神经评估的患者中，≥2/5、≥3/5、≥4/5或5/5个区域的DIS对MS诊断的敏感性也降低（96%、83%、61%、30%），特异性增加（44%、83%、100%、100%）。我们提出了一种基于满足的DIS区域数量的首发脱髓鞘事件患者MS诊断算法。
在首发脱髓鞘事件的患者中，MS中典型受累的≥4个区域的DIS具有高度特异性，表明假阳性结果和误诊的风险极低。对所有疑似MS的患者使用≥4个区域的DIS将减少随访MRI或脑脊液检查的需求，简化诊断过程。局限性包括发病时视神经炎患者比例过高、脑脊液检查率低以及缺乏光学相干断层扫描数据。
