BACKGROUND: Early diagnosis and treatment of patients with multiple sclerosis (MS) are associated with better outcomes; however, diagnostic delays remain a major problem. OBJECTIVE: Describe the prevalence, determinants and consequences of delayed diagnoses. METHODS: This single-centre ambispective study analysed 146 adult relapsing-remitting MS patients (2016-2021) for frequency and determinants of diagnostic delays and their associations with clinical, cognitive, imaging and biochemical measures. RESULTS: Diagnostic delays were identified in 77 patients (52.7%), including 42 (28.7%) physician-dependent cases and 35 (24.0%) patient-dependent cases. Diagnosis was delayed in 22 (15.1%) patients because of misdiagnosis by a neurologist. A longer diagnostic delay was associated with trends towards greater Expanded Disability Status Scale (EDSS) scores (B = 0.03; p = 0.034) and greater z-score of the blood neurofilament light chain (B = 0.35; p = 0.031) at the time of diagnosis. Compared with patients diagnosed at their first clinical relapse, patients with a history of >1 relapse at diagnosis (n = 63; 43.2%) had a trend towards greater EDSS scores (B = 0.06; p = 0.006) and number of total (B = 0.13; p = 0.040) and periventricular (B = 0.06; p = 0.039) brain lesions. CONCLUSION: Diagnostic delays in MS are common, often determined by early misdiagnosis and associated with greater disease burden.

Advanced Clinical Imaging Technology Siemens Healthineers International AG Lausanne Switzerland Department of Radiology Lausanne University Hospital and University of Lausanne Lausanne Switzerland Signal Processing Laboratory Lausanne Switzerland

Department of Neurology and Center of Clinical Neuroscience 1st Faculty of Medicine and General University Hospital Charles University Prague Czech Republic

Department of Neurology and Center of Clinical Neuroscience 1st Faculty of Medicine and General University Hospital Charles University Prague Czech Republic Department of Radiology Charles University Prague 1st Faculty of Medicine and General University Hospital Prague Czech Republic

Department of Neurology University Hospital and University of Basel Basel Switzerland

Department of Radiology Charles University Prague 1st Faculty of Medicine and General University Hospital Prague Czech Republic

Departments of Medicine Biomedicine and Clinical Research Neurologic Clinic and Policlinic University Hospital Basel University of Basel Basel Switzerland

Institute of Medical Biochemistry and Laboratory Diagnostics 1st Faculty of Medicine and General University Hospital Charles University Prague Czech Republic

Multiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience Departments of Biomedicine and Clinical Research University Hospital and University of Basel Basel Switzerland

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Brown JWL, Coles A, Horakova D, et al.. Association of initial disease-modifying therapy with later conversion to secondary progressive multiple sclerosis. JAMA 2019; 321: 175–187. PubMed PMC

Giovannoni G, Butzkueven H, Dhib-Jalbut S, et al.. Brain health: time matters in multiple sclerosis. Mult Scler Relat Disord 2016; 9(suppl 1): S5–S48. PubMed

Clinical guideline [CG186] multiple sclerosis in adults: management. 2019. https://www.nice.org.uk/guidance/cg186

Hobart J, Bowen A, Pepper G, et al.. International consensus on quality standards for brain health-focused care in multiple sclerosis. Mult Scler 2019; 25(13): 1809–1818. PubMed PMC

Solomon AJ, Marrie RA, Viswanathan S, et al.. global barriers to the diagnosis of multiple sclerosis: data from the multiple sclerosis international federation atlas of MS, third edition. Neurology 2023; 101(6): e624–e635. PubMed PMC

Tintore M, Cobo-Calvo A, Carbonell P, et al.. Effect of changes in MS diagnostic criteria over 25 years on time to treatment and prognosis in patients with clinically isolated syndrome. Neurology 2021; 97: e1641–e1652. PubMed

Ghiasian M, Faryadras M, Mansour M, et al.. Assessment of delayed diagnosis and treatment in multiple sclerosis patients during 1990-2016. Acta Neurol Belg 2021; 121(1): 199–204. PubMed

Cárdenas-Robledo S, Lopez-Reyes L, Arenas-Vargas LE, et al.. Delayed diagnosis of multiple sclerosis in a low prevalence country. Neurol Res 2021; 43(7): 521–527. PubMed

Kingwell E, Leung AL, Roger E, et al.. Factors associated with delay to medical recognition in two Canadian multiple sclerosis cohorts. J Neurol Sci 2010; 292: 57–62. PubMed

Marrie RA, Cutter G, Tyry T, et al.. Changes in the ascertainment of multiple sclerosis. Neurology 2005; 65: 1066–1070. PubMed

Kaufmann M, Kuhle J, Puhan MA, et al.. Factors associated with time from first-symptoms to diagnosis and treatment initiation of multiple sclerosis in Switzerland. Mult Scler J Exp Transl Clin 2018; 4(4): 2055217318814562. PubMed PMC

Willumsen JS, Aarseth JH, Myhr KM, et al.. High incidence and prevalence of MS in more and Romsdal county, Norway, 1950-2018. Neurol Neuroimmunol Neuroinflamm 2020; 7: e713. PubMed PMC

Blaschke SJ, Ellenberger D, Flachenecker P, et al.. Time to diagnosis in multiple sclerosis: Epidemiological data from the German multiple sclerosis registry. Mult Scler 2022; 28(6): 865–871. PubMed

Jakimovski D, Kavak KS, Zakalik K, et al.. Improvement in time to multiple sclerosis diagnosis: 25-year retrospective analysis from New York State MS CONSORTIUM (NYSMSC). Mult Scler 2023; 29(6): 753–756. PubMed

Khedr EM, El Malky I, Hussein HB, et al.. Multiple sclerosis diagnostic delay and its associated factors in Upper Egyptian patients. Sci Rep 2023; 13: 2249. PubMed PMC

Marrie RA, Horwitz R, Cutter G, et al.. Comorbidity delays diagnosis and increases disability at diagnosis in MS. Neurology 2009; 72: 117–124. PubMed PMC

Thormann A, Sorensen PS, Koch-Henriksen N, et al.. Comorbidity in multiple sclerosis is associated with diagnostic delays and increased mortality. Neurology 2017; 89: 1668–1675. PubMed

Aires A, Barros A, Machado C, et al.. Diagnostic delay of multiple sclerosis in a Portuguese population. Acta Med Port 2019; 32: 289–294. PubMed

Patti F, Chisari CG, Arena S, et al.. Factors driving delayed time to multiple sclerosis diagnosis: Results from a population-based study. Mult Scler Relat Disord 2022; 57: 103361. PubMed

Fernández O, Fernández V, Arbizu T, et al.. Characteristics of multiple sclerosis at onset and delay of diagnosis and treatment in Spain (the Novo Study). J Neurol 2010; 257(9): 1500–1507. PubMed

Kelly SB, Chaila E, Kinsella K, et al.. Multiple sclerosis, from referral to confirmed diagnosis: an audit of clinical practice. Mult Scler 2011; 17(8): 1017–1021. PubMed

Adamec I, Barun B, Gabelić T, et al.. Delay in the diagnosis of multiple sclerosis in Croatia. Clin Neurol Neurosurg 2013; 115(suppl 1): S70–S72. PubMed

Gasperi C, Hapfelmeier A, Daltrozzo T, et al.. Systematic assessment of medical diagnoses preceding the first diagnosis of multiple sclerosis. Neurology. Epub ahead of print 26 April 2021. DOI: 10.1212/WNL.0000000000012074 PubMed DOI

Thompson AJ, Banwell BL, Barkhof F, et al.. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol 2018; 17: 162–173. PubMed

Dusankova JB, Kalincik T, Havrdova E, et al.. Cross cultural validation of the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) and the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS). Clin Neuropsychol 2012; 26(7): 1186–1200. PubMed

Rao SM. A manual for the brief repeatable battery of neuropsychological tests in multiple sclerosis. New York: National Multiple Sclerosis Society, 1990.

Fartaria MJ, Bonnier G, Roche A, et al.. Automated detection of white matter and cortical lesions in early stages of multiple sclerosis. J Magn Reson Imaging 2016; 43(6): 1445–1454. PubMed

Schmitter D, Roche A, Maréchal B, et al.. An evaluation of volume-based morphometry for prediction of mild cognitive impairment and Alzheimer’s disease. Neuroimage Clin 2015; 7: 7–17. PubMed PMC

Andelova M, Uher T, Krasensky J, et al.. Additive effect of spinal cord volume, diffuse and focal cord pathology on disability in multiple sclerosis. Front Neurol 2019; 10: 820. PubMed PMC

Uher T, Havrdova EK, Benkert P, et al.. Measurement of neurofilaments improves stratification of future disease activity in early multiple sclerosis. Mult Scler 2021; 27(13): 2001–2013. PubMed

Benkert P, Meier S, Schaedelin S, et al.. Serum neurofilament light chain for individual prognostication of disease activity in people with multiple sclerosis: a retrospective modelling and validation study. Lancet Neurol 2022; 21(3): 246–257. PubMed

Marrie RA, Horwitz R, Cutter G, et al.. The burden of mental comorbidity in multiple sclerosis: frequent, underdiagnosed, and undertreated. Mult Scler 2009; 15(3): 385–392. PubMed

Cobo-Calvo A, Tur C, Otero S, et al.. Very early treatment decreases the risk of long-term disability in patients with CIS or early MS. Amsterdam, The Netherlands: ECTRIMS; 2022.

Marrie RA, Allegretta M, Barcellos LF, et al.. From the prodromal stage of multiple sclerosis to disease prevention. Nat Rev Neurol 2022; 18(9): 559–572. PubMed

Kalincik T, Butzkueven H. Observational data: understanding the real MS world. Mult Scler 2016; 22(13): 1642–1648. PubMed