Clinical and laboratory parameters by age for patients diagnosed with multiple sclerosis between 2000 and 2015
Abstract
Aim of the study: To compare the demographic, clinical and laboratory characteristics of patients with multiple sclerosis (MS) analysed based on the age at which they were diagnosed.
Clinical rationale for the study: Most cases of MS are diagnosed between the ages of 20 and 40 years, but the clinical characteristics of patients with MS over this age range have rarely been studied.
Material and methods: 182 patients diagnosed with MS between 2000 and 2015 were divided into four groups by age at diagnosis: < 30 years (n = 62), 30–39 years (n = 54), 40–49 years (n = 27), and ≥ 50 years (n = 39). The demographic, clinical and laboratory features of each age group were investigated and between-groups comparisons analysed.
Results: There were no significant differences in the female-to-male ratio between groups, which was close to 3:1 in every group (p = 0.98). Motor symptoms were more common as the first manifestation of MS with increasing age (< 30: 19.3%; 30–39: 37.0%; 40–49: 44.4%; ≥ 50: 61.5%). Visual and sensory symptoms were responsible for nearly half of first manifestations in patients < 30 to 49, but affected a significantly lower proportion of patients in the oldest group (p = 0.01). Median (interquartile range [IQR]) Expanded Disability Status Scale at diagnosis was higher with advancing age (2 [1.5–3], 2.25 [1.5–3.5], 3 [2–3.5], and 3.5 [3–5]; p < 0.01). There was also a higher proportion of patients with progressive forms of the disease with age, especially primary progressive MS (0.0%, 3.7%, 14.8%, and 51.3%; p < 0.01). The median (IQR) time needed to confirm the diagnosis of MS became significantly longer as age increased (7 [2–25], 9 [2–32], 12 [6–58], and 26 [12–60] months; p < 0.01). In laboratory tests, significant differences were found only in the rate of post-contrast enhancement by magnetic resonance imaging, which was lower in the older age groups (63.2%, 50.0%, 31.6%, and 30.0%; p < 0.01).
Conclusions and clinical implications: Our study indicates significant differences in the demographic and clinical picture of MS depending on the age of the patient at diagnosis. Diagnostic delay in older patients is a common problem, and this study shows the features of later forms of MS to help inform neurologists and improve time to diagnosis.
Keywords: Multiple sclerosisage at diagnosistime from first symptoms to diagnosisclinical differences
References
- Thompson A, Baranzini S, Geurts J, et al. Multiple sclerosis. The Lancet. 2018; 391(10130): 1622–1636.
- Martinelli V, Rodegher M, Moiola L, et al. Late onset multiple sclerosis: clinical characteristics, prognostic factors and differential diagnosis. Neurol Sci. 2004; 25 Suppl 4: S350–S355.
- Ascherio A, Munger KL. Epidemiology of multiple sclerosis: from risk factors to prevention-an update. Semin Neurol. 2016; 36(2): 103–114.
- Confavreux C, Vukusic S. Natural history of multiple sclerosis: a unifying concept. Brain. 2006; 129(Pt 3): 606–616.
- Przybek-Skrzypecka J, Małecka I, Członkowska A, et al. Demographic and clinical profile of patients with multiple sclerosis diagnosed over the last 30 years according to different diagnostic criteria. Neurol Neurochir Pol. 2020; 54(2): 169–175.
- Polliack ML, Barak Y, Achiron A. Late-onset multiple sclerosis. J Am Geriatr Soc. 2001; 49(2): 168–171.
- de Seze J, Delalande S, Michelin E, et al. Late onset multiple sclerosis. Rev Neurol (Paris). 2002; 158(11): 1082–1087.
- Tremlett H, Devonshire V. Is late-onset multiple sclerosis associated with a worse outcome? Neurology. 2006; 67(6): 954–959.
- Kis B, Rumberg B, Berlit P. Clinical characteristics of patients with late-onset multiple sclerosis. J Neurol. 2008; 255(5): 697–702.
- Arias M, Dapena D, Arias-Rivas S, et al. Late onset multiple sclerosis. Neurologia. 2011; 26(5): 291–296.
- Cossburn M, Ingram G, Hirst C, et al. Age at onset as a determinant of presenting phenotype and initial relapse recovery in multiple sclerosis. Mult Scler. 2012; 18(1): 45–54.
- Bove RM, Healy B, Augustine A, et al. Effect of gender on late-onset multiple sclerosis. Mult Scler. 2012; 18(10): 1472–1479.
- Roohani P, Emiru T, Carpenter A, et al. Late onset multiple sclerosis: Is it really late onset? Mult Scler Relat Disord. 2014; 3(4): 444–449.
- Shirani A, Zhao Y, Petkau J, et al. Multiple sclerosis in older adults: the clinical profile and impact of interferon Beta treatment. Biomed Res Int. 2015; 2015: 451912.
- D'Amico E, Patti F, Zanghì A, et al. Late-onset and young-onset relapsing-remitting multiple sclerosis: evidence from a retrospective long-term follow-up study. Eur J Neurol. 2018; 25(12): 1425–1431.
- Aires A, Barros A, Machado C, et al. Diagnostic delay of multiple sclerosis in a Portuguese population. Acta Med Port. 2019; 32(4): 289–294.
- Brola W, Sobolewski P, Żak M, et al. Profile of Polish patients with primary progressive multiple sclerosis. Mult Scler Relat Disord. 2019; 33: 33–38.
- Fernández O, Fernández V, Arbizu T, et al. Novo Group. Characteristics of multiple sclerosis at onset and delay of diagnosis and treatment in Spain (the Novo Study). J Neurol. 2010; 257(9): 1500–1507.
- 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.
- Celius EG, Smestad C. Change in sex ratio, disease course and age at diagnosis in Oslo MS patients through seven decades. Acta Neurol Scand Suppl. 2009(189): 27–29.
- Lavorgna L, Borriello G, Esposito S, et al. Impact of early diagnosis on clinical characteristics of an Italian sample of people with multiple sclerosis recruited online. Mult Scler Relat Disord. 2019; 27: 239–246.
- Marrie RA, Horwitz R, Cutter G, et al. Comorbidity delays diagnosis and increases disability at diagnosis in MS. Neurology. 2009; 72(2): 117–124.
- Thormann A, Sørensen PS, Koch-Henriksen N, et al. Comorbidity in multiple sclerosis is associated with diagnostic delays and increased mortality. Neurology. 2017; 89(16): 1668–1675.
- Lotti CB, Oliveira AS, Bichuetti DB, et al. Late onset multiple sclerosis: concerns in aging patients. Arq Neuropsiquiatr. 2017; 75(7): 451–456.
- Bermel RA, Rae-Grant AD, Fox RJ. Diagnosing multiple sclerosis at a later age: more than just progressive myelopathy. Mult Scler. 2010; 16(11): 1335–1340.
- Weinshenker BG, Bass B, Rice GP, et al. The natural history of multiple sclerosis: a geographically based study. I. Clinical course and disability. Brain. 1989; 112 ( Pt 1): 133–146.
- Vukusic S, Confavreux C. Primary and secondary progressive multiple sclerosis. J Neurol Sci. 2003; 206(2): 153–155.
- Riise T, Grønning M, Fernández O, et al. Early prognostic factors for disability in multiple sclerosis, a European multicenter study. Acta Neurol Scand. 1992; 85(3): 212–218.
- Trojano M, Avolio C, Manzari C, et al. Multivariate analysis of predictive factors of multiple sclerosis course with a validated method to assess clinical events. J Neurol Neurosurg Psychiatry. 1995; 58(3): 300–306.
- Hooge JP, Redekop WK. Multiple sclerosis with very late onset. Neurology. 1992; 42(10): 1907–1910.
- Phadke JG. Clinical aspects of multiple sclerosis in north-east Scotland with particular reference to its course and prognosis. Brain. 1990; 113 ( Pt 6): 1597–1628.
- White AD, Swingler RJ, Compston DA. Features of multiple sclerosis in older patients in South Wales. Gerontology. 1990; 36(3): 159–164.
- Bergamaschi R, Berzuini C, Romani A, et al. Predicting secondary progression in relapsing-remitting multiple sclerosis: a Bayesian analysis. J Neurol Sci. 2001; 189(1-2): 13–21.
- Confavreux C, Vukusic S, Adeleine P. Early clinical predictors and progression of irreversible disability in multiple sclerosis: an amnesic process. Brain. 2003; 126(Pt 4): 770–782.
- Amato MP, Ponziani G, Bartolozzi ML, et al. A prospective study on the natural history of multiple sclerosis: clues to the conduct and interpretation of clinical trials. J Neurol Sci. 1999; 168(2): 96–106.
- Vukusic S, Confavreux C, Confavreux C, et al. Natural history of multiple sclerosis: a unifying concept. Brain. 2006; 129(Pt 3): 606–616.
- Ramachandran S, Strange RC, Jones PW, et al. Associations between onset age and disability in multiple sclerosis patients studied using MSSS and a progression model. Mult Scler Relat Disord. 2014; 3(5): 593–599.
- Alroughani R, Akhtar S, Ahmed S, et al. Is Time to Reach EDSS 6.0 Faster in Patients with Late-Onset versus Young-Onset Multiple Sclerosis? PLoS One. 2016; 11(11): e0165846.
- Cierny D, Lehotsky J, Hanysova S, et al. The age at onset in Multiple Sclerosis is associated with patient's prognosis. Bratisl Lek Listy. 2017; 118(6): 374–377.
- Scalfari A, Neuhaus A, Daumer M, et al. The natural history of multiple sclerosis: a geographically based study 10: relapses and long-term disability. Brain. 2010; 133(Pt 7): 1914–1929.
- Guillemin F, Baumann C, Epstein J, et al. LORSEP Group. Older age at multiple sclerosis onset is an independent factor of poor prognosis: A population-based cohort study. Neuroepidemiology. 2017; 48(3-4): 179–187.
- Jasek Ł, Śmigielski J, Siger M. Late onset multiple sclerosis - multiparametric MRI characteristics. Neurol Neurochir Pol. 2020; 54(3): 265–271.
- Noseworthy J, Paty D, Wonnacott T, et al. Multiple sclerosis after age 50. Neurology. 1983; 33(12): 1537–1544.