Brownlee, Wallace J; Foster, Michael A; Pontillo, Giuseppe; Davagnanam, Indran; Collorone, Sara; Prados, Ferran; Kanber, Baris; ... Ciccarelli, Olga; + view all 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; - view fewer (2025) Investigating Whether Dissemination in Time Is Essential to Diagnose Relapsing Multiple Sclerosis. Neurology , 104 (7) , Article e210274. 10.1212/WNL.0000000000210274.

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Abstract

Background and Objectives: 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. / Methods: 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. / Results: 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. / Discussion: 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.

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