Diagnostic errors in multiple sclerosis (MS) impact patients and healthcare systems.
Objectives:
This study aimed to determine the prevalence of MS misdiagnosis and underdiagnosis, time delay in reaching a correct diagnosis and potential impact of sex.
Methods:
Systematic review and meta-analysis on MS diagnostic errors.
Results:
Out of 3910 studies, we included 62 for a qualitative synthesis and 24 for meta-analyses. Frequency of misdiagnosis (incorrect assignment of an MS diagnosis) ranged from 5% to 41%, with a pooled proportion based on six studies of 15% (95% CI: 9%–26%, n = 1621). The delay to rectify a misdiagnosis ranged from 0.3 to 15.9 years. Conversely, underdiagnosis (unrecognized diagnosis of MS) ranged from 3% to 58%, with a pooled proportion in four studies of 36% (95% CI: 20%–55%, n = 728). Pooling seven studies comprising 2851 individuals suggested a diagnostic delay to establish a correct MS diagnosis of 17.3 months (95% CI: 11.9–22.7) in patients underdiagnosed. In a meta-analysis of five studies, women were 2.1 times more likely to be misdiagnosed with MS compared to men (odds ratio, 95% CI: 1.53–2.86).
Conclusion:
This study provides summary-level evidence for the high prevalence of MS misdiagnosis and underdiagnosis. Future studies are needed to understand the causes of these diagnostic challenges in MS care.
AbdulaRKurmanjiMMohammedZ, et al. Revision of multiple sclerosis cases according to new 2017 McDonald criteria among diagnosed patients in Sulaimani city. J Sulaimani Med Coll2021; 11: 323–333.
2.
Caparó-ZamalloaCCastro-SuarezSCortez-EscalanteJ, et al. Brainstem syndrome at onset is related to an early MS diagnosis in Peru: A national referral center cohort. Heliyon2021; 7: e08069.
3.
EngellT. A clinico-pathoanatomical study of multiple sclerosis diagnosis. Acta Neurol Scand1988; 78: 39–44.
4.
GaitánMISanchezMFarezMF, et al. The frequency and characteristics of multiple sclerosis misdiagnosis in Latin America: A referral center study in Buenos Aires, Argentina. Mult Scler2021: 13524585211067521.
5.
KaiseyMSolomonAJLuuMGiesserBSSicotteNL. Incidence of multiple sclerosis misdiagnosis in referrals to two academic centers. Mult Scler Relat Dis2019; 30: 51–56.
6.
MidagliaLSastre-GarrigaJPappollaA, et al. The frequency and characteristics of MS misdiagnosis in patients referred to the multiple sclerosis centre of Catalonia. Mult Scler2021; 27: 913–921.
7.
PoserCM. Misdiagnosis of multiple sclerosis and beta-interferon. Lancet1997; 349: 1916.
8.
de Souza TieppoEMSilvaGDda SilvaTFF, et al. Misdiagnosis in multiple sclerosis in a Brazilian reference center: Clinical, radiological, laboratory profile and failures in the diagnostic process-Cohort study. Mult Scler2023; 29: 1755–1764.
9.
WangYBou RjeilyNKoshorekJ, et al. Clinical and radiologic characteristics associated with multiple sclerosis misdiagnosis at a tertiary referral center in the United States. Mult Scler J2023; 29: 1428–1436.
10.
UherTAdzimaASrpovaB, et al. Diagnostic delay of multiple sclerosis: Prevalence, determinants and consequences. Mult Scler2023; 29: 1437–1451.
11.
PiehlF. Current and emerging disease-modulatory therapies and treatment targets for multiple sclerosis. J Intern Med2021; 289: 771–791.
12.
SolomonAJMarrieRAViswanathanS, et al. Global barriers to the diagnosis of multiple sclerosis: Data from the Multiple Sclerosis International Federation Atlas of MS. Neurology2023; 101: e624–e635.
13.
GiovannoniGButzkuevenHDhib-JalbutS, et al. Brain health: Time matters in multiple sclerosis. Mult Scler Relat Disord2016; 9: S5–S48.
14.
MidagliaLSastre-GarrigaJPappollaA, et al. The frequency and characteristics of MS misdiagnosis in patients referred to the multiple sclerosis centre of Catalonia. Mult Scler2021; 27: 913–921.
15.
IvaniukAMarusichTSolodovnikovaY, et al. Is initial misdiagnosis associated with reaching disability milestones in patients with multiple sclerosis?Medicina2020; 56: 170.
16.
AiresABarrosAMachadoC, et al. Diagnostic delay of multiple sclerosis in a Portuguese population. Acta Med Port2019; 32: 289–294.
17.
SolomonAJWeinshenkerBG. Misdiagnosis of multiple sclerosis: Frequency, causes, effects, and prevention. Curr Neurol Neurosci Rep2013; 13: 403.
18.
Caparó-ZamalloaCCastro-SuarezSCortez-EscalanteJ, et al. Brainstem syndrome at onset is related to an early MS diagnosis in Peru: A national referral center cohort. Heliyon2021; 7: e08069.
19.
EngellT. A clinic-pathoanatomical study of multiple sclerosis diagnosis. Acta Neurol Scand1988; 78: 39–44.
20.
De Souza TieppoEMSilvaGDDa SilvaTFF, et al. Misdiagnosis in multiple sclerosis in a Brazilian reference center: Clinical, radiological, laboratory profile and failures in the diagnostic process-Cohort study. Mult Scler2023; 29: 1755–1764.
21.
WangYBou RjeilyNKoshorekJ, et al. Clinical and radiologic characteristics associated with multiple sclerosis misdiagnosis at a tertiary referral center in the United States. Mult Scler J2023; 29: 1428–1436.
22.
PoserCM. Misdiagnosis of multiple sclerosis and beta-interferon. Lancet1997; 349: 1916.
23.
De SeabraMMAbreuPMMendonçaMT, et al. Diagnostic revisions in multiple sclerosis. Clin Exp Neuroimmunol2020; 11: 171–175.
24.
AbdulaRKurmanjiMMohammedZ, et al. Revision of multiple sclerosis cases according to new 2017 McDonald criteria among diagnosed patients in Sulaimani city. J Sulaimani Med Coll2021; 11: 323–333.
25.
SolomonAJKleinEPBourdetteD. ‘Undiagnosing’ multiple sclerosis: The challenge of misdiagnosis in MS. Neurology2012; 78: 1986–1991.
26.
LevinNMorMBen-HurT. Patterns of misdiagnosis of multiple sclerosis. Isr Med Assoc J2003; 5: 489–490.
27.
QiuWWuJSCastleyA, et al. Clinical profile and HLA-DRB1 genotype of late onset multiple sclerosis in Western Australia. J Clin Neurosci2010; 17: 1009–1013.
28.
KhedrEMEl MalkyIHusseinHB, et al. Multiple sclerosis diagnostic delay and its associated factors in Upper Egyptian patients. Sci Rep2023; 13: 2249.
29.
AdamecIBarunBGabelićT, et al. Delay in the diagnosis of multiple sclerosis in Croatia. Clin Neurol Neurosurg2013; 115(suppl. 1): S70–S72.
30.
FernándezOFernándezVArbizuT, et al. Characteristics of multiple sclerosis at onset and delay of diagnosis and treatment in Spain (the Novo Study). J Neurol2010; 257: 1500–1507.
31.
JakimovskiDKavakKSZakalikK, et al. Improvement in time to multiple sclerosis diagnosis: 25-year retrospective analysis from New York State MS Consortium (NYSMSC). Mult Scler J2023; 29: 753–756.
32.
KaufmannMKuhleJPuhanMA, 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. Epub ahead of print 6December2018. DOI: 10.1177/2055217318814562.
33.
KingwellELeungALRogerE, et al. Factors associated with delay to medical recognition in two Canadian multiple sclerosis cohorts. J Neurol Sci2010; 292: 57–62.
34.
MobasheriFJaberiARHasanzadehJ, et al. Multiple sclerosis diagnosis delay and its associated factors among Iranian patients. Clin Neurol Neurosurg2020; 199: 106278.
35.
PattiFChisariCGArenaS, et al. Factors driving delayed time to multiple sclerosis diagnosis: Results from a population-based study. Mult Scler Relat Disord2022; 57: 103361.
36.
SteenhofMStenagerENielsenNM, et al. Familial multiple sclerosis patients have a shorter delay in diagnosis than sporadic cases. Mult Scler Relat Disord2019; 32: 97–102.
37.
WillumsenJSAarsethJHMyhrK-M, et al. High incidence and prevalence of MS in Møre and Romsdal County, Norway, 1950–2018. Neurol Neuroimmunol Neuroinflamm2020; 7: e713.
38.
ZakariaMZamzamDAAbdel HafeezMA, et al. Clinical characteristics of patients with multiple sclerosis enrolled in a new registry in Egypt. Mult Scler Relat Disord2016; 10: 30–35.
39.
Cárdenas-RobledoSLopez-ReyesLArenas-VargasLE, et al. Delayed diagnosis of multiple sclerosis in a low prevalence country. Neurol Res2021; 43: 521–527.
40.
GhiasianMFaryadrasMMansourM, et al. Assessment of delayed diagnosis and treatment in multiple sclerosis patients during 1990-2016. Acta Neurol Belg2021; 121: 199–204.
41.
ThormannASørensenPSKoch-HenriksenN, et al. Comorbidity in multiple sclerosis is associated with diagnostic delays and increased mortality. Neurology2017; 89: 1668–1675.
42.
SolomonAJCorboyJR. The tension between early diagnosis and misdiagnosis of multiple sclerosis. Nat Rev Neurol2017; 13: 567–572.
43.
MakaryMADanielM. Medical error-the third leading cause of death in the US. BMJ2016; 353: i2139.
44.
IneichenBVMoridiTGranbergT, et al. Rituximab treatment for multiple sclerosis. Mult Scler2020; 26: 137–152.
45.
Cobo-CalvoATurCOtero-RomeroS, et al. Association of very early treatment initiation with the risk of long-term disability in patients with a first demyelinating event. Neurology2023; 101: e1280–e1292.
46.
WalzlDSolomonAJStoneJ. Functional neurological disorder and multiple sclerosis: A systematic review of misdiagnosis and clinical overlap. J Neurol2022; 269: 654–663.
47.
WalzlDCarsonAJStoneJ. The misdiagnosis of functional disorders as other neurological conditions. J Neurol2019; 266: 2018–2026.
48.
HambergKRisbergGJohanssonEE, et al. Gender bias in physicians’ management of neck pain: A study of the answers in a Swedish national examination. J Womens Health Gend Based Med2002; 11: 653–666.
49.
ZwaanLSchiffGDSinghH. Advancing the research agenda for diagnostic error reduction. BMJ Qual Saf2013; 22: ii52–ii57.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
