open access

Vol 57, No 3 (2023)
Research Paper
Submitted: 2023-02-10
Accepted: 2023-04-07
Published online: 2023-05-05
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Prevalence and prognostic value of prodromal symptoms in relapsing-remitting multiple sclerosis

Karolina Kania1, Wojciech Ambrosius1, Klara Dyczkowska2, Wojciech Kozubski1, Alicja Kalinowska-Lyszczarz13
·
Pubmed: 37144905
·
Neurol Neurochir Pol 2023;57(3):289-296.
Affiliations
  1. Department of Neurology, Poznan University of Medical Sciences, Poznan, Poland
  2. Poznan University of Medical Sciences, Poznan, Poland
  3. Division of Neurochemistry and Neuropathology, Department of Neurology, Poznan University of Medical Sciences, Poznan, Poland

open access

Vol 57, No 3 (2023)
Research papers
Submitted: 2023-02-10
Accepted: 2023-04-07
Published online: 2023-05-05

Abstract

Introduction. Several studies have suggested the possibility that disease prodromes might occur months or even years before a multiple sclerosis diagnosis. Objectives. To describe the profile of prodromal symptoms and the possible relationship between the occurrence of individual symptoms and clinical course characteristics in patients with relapsing-remitting multiple sclerosis (RRMS), and to assess their role as predictors of further disease course. Material and methods. The cohort included 564 patients with RRMS. Patients were stratified based on their current EDSS score, and the annual EDSS growth rate was calculated. Logistic Regression Analysis was used to study the relationship between prodromal symptoms and disease progression. Results. The most commonly reported prodromal symptom was fatigue (42%). The following symptoms were significantly more common in women than in men: headache (39.7% vs. 26.5%, p < 0.05), excessive sleepiness (19.1% vs. 11.1%, p < 0.05) and constipation (18.0% vs. 11.1%, p < 0.05). Prodromal urinary and cognitive disturbances, fatigue and pain complaints were significantly more common in patients with the highest annual EDSS increase (p < 0.05). Multivariate analysis revealed some potential predictors of long-term disability progression: hesitancy in starting urination predicted EDSS increase by 0.6 point (p < 0.05), while deterioration in everyday functioning because of cognitive disturbances, and pain complaints, were associated with an EDSS increase of 0.5 (p < 0.05), and 0.4 (p < 0.05), respectively. Conclusions. Prodromal pain, urinary and cognitive complaints (especially when these lead to deterioration of everyday functioning) were associated with a higher EDSS increase rate, and may thus be regarded as possible predictors of worse clinical outcomes in RRMS patients.

Abstract

Introduction. Several studies have suggested the possibility that disease prodromes might occur months or even years before a multiple sclerosis diagnosis. Objectives. To describe the profile of prodromal symptoms and the possible relationship between the occurrence of individual symptoms and clinical course characteristics in patients with relapsing-remitting multiple sclerosis (RRMS), and to assess their role as predictors of further disease course. Material and methods. The cohort included 564 patients with RRMS. Patients were stratified based on their current EDSS score, and the annual EDSS growth rate was calculated. Logistic Regression Analysis was used to study the relationship between prodromal symptoms and disease progression. Results. The most commonly reported prodromal symptom was fatigue (42%). The following symptoms were significantly more common in women than in men: headache (39.7% vs. 26.5%, p < 0.05), excessive sleepiness (19.1% vs. 11.1%, p < 0.05) and constipation (18.0% vs. 11.1%, p < 0.05). Prodromal urinary and cognitive disturbances, fatigue and pain complaints were significantly more common in patients with the highest annual EDSS increase (p < 0.05). Multivariate analysis revealed some potential predictors of long-term disability progression: hesitancy in starting urination predicted EDSS increase by 0.6 point (p < 0.05), while deterioration in everyday functioning because of cognitive disturbances, and pain complaints, were associated with an EDSS increase of 0.5 (p < 0.05), and 0.4 (p < 0.05), respectively. Conclusions. Prodromal pain, urinary and cognitive complaints (especially when these lead to deterioration of everyday functioning) were associated with a higher EDSS increase rate, and may thus be regarded as possible predictors of worse clinical outcomes in RRMS patients.

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Keywords

multiple sclerosis, prodromes, disease predictors, RIS, preclinical phase

About this article
Title

Prevalence and prognostic value of prodromal symptoms in relapsing-remitting multiple sclerosis

Journal

Neurologia i Neurochirurgia Polska

Issue

Vol 57, No 3 (2023)

Article type

Research Paper

Pages

289-296

Published online

2023-05-05

Page views

1532

Article views/downloads

527

DOI

10.5603/PJNNS.a2023.0035

Pubmed

37144905

Bibliographic record

Neurol Neurochir Pol 2023;57(3):289-296.

Keywords

multiple sclerosis
prodromes
disease predictors
RIS
preclinical phase

Authors

Karolina Kania
Wojciech Ambrosius
Klara Dyczkowska
Wojciech Kozubski
Alicja Kalinowska-Lyszczarz

References (38)
  1. Tremlett H, Munger KL, Makhani N, et al. The multiple sclerosis prodrome. Nat Rev Neurol. 2021; 17(8): 515–521.
  2. Thompson AJ, Banwell BL, Barkhof F, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018; 17(2): 162–173.
  3. Chalmer TA, Baggesen LM, Nørgaard M, et al. Danish Multiple Sclerosis Group. Early versus later treatment start in multiple sclerosis: a register-based cohort study. Eur J Neurol. 2018; 25(10): 1262–e110.
  4. Kavaliunas A, Manouchehrinia A, Stawiarz L, et al. Importance of early treatment initiation in the clinical course of multiple sclerosis. Mult Scler. 2017; 23(9): 1233–1240.
  5. Kalinowska-Łyszczarz A. Multiple sclerosis and related disorders: where do we stand in 2022? Neurol Neurochir Pol. 2022; 56(3): 197–200.
  6. Manouchehri N, Shirani A, Salinas VH, et al. Clinical trials in multiple sclerosis: past, present, and future. Neurol Neurochir Pol. 2022; 56(3): 228–235.
  7. Okuda DT, Mowry EM, Cree BAC, et al. Incidental MRI anomalies suggestive of multiple sclerosis: the radiologically isolated syndrome. Neurology. 2009; 72(9): 800–805.
  8. Lebrun-Frenay C, Kantarci O, Siva A, et al. 10-year RISC study group on behalf of SFSEP, OFSEP. Radiologically isolated syndrome: 10-year risk estimate of a clinical event. Ann Neurol. 2020; 88(2): 407–417.
  9. Tremlett H, Munger KL, Makhani N. The multiple sclerosis prodrome: evidence to action. Front Neurol. 2021; 12: 761408.
  10. Hustad E, Aasly JO. Clinical and imaging markers of prodromal Parkinson's disease. Front Neurol. 2020; 11: 395.
  11. Benasi G, Fava GA, Guidi J. Prodromal symptoms in depression: a systematic review. Psychother Psychosom. 2021; 90(6): 365–372.
  12. Pimentel M, Chang M, Chow EJ, et al. Identification of a prodromal period in Crohn's disease but not ulcerative colitis. Am J Gastroenterol. 2000; 95(12): 3458–3462.
  13. Sinay V, Perez Akly M, Zanga G, et al. School performance as a marker of cognitive decline prior to diagnosis of multiple sclerosis. Mult Scler. 2015; 21(7): 945–952.
  14. Wijnands JMA, Zhu F, Kingwell E, et al. Prodrome in relapsing-remitting and primary progressive multiple sclerosis. Eur J Neurol. 2019; 26(7): 1032–1036.
  15. Jorge A, André A, Rocha AL, et al. Defining the prodromal phase of multiple sclerosis based on healthcare access in a Portuguese population - ProdMS study. Mult Scler Relat Disord. 2021; 55: 103154.
  16. Yusuf FLA, Wijnands JMa, Kingwell E, et al. Fatigue, sleep disorders, anaemia and pain in the multiple sclerosis prodrome. Mult Scler. 2021; 27(2): 290–302.
  17. Yusuf FLA, Ng BC, Wijnands JMA, et al. A systematic review of morbidities suggestive of the multiple sclerosis prodrome. Expert Rev Neurother. 2020; 20(8): 799–819.
  18. Marrie RA, Wijnands JMA, Kingwell E, et al. Higher health care use before a clinically isolated syndrome with or without subsequent MS. Mult Scler Relat Disord. 2019; 35: 42–49.
  19. Brola W, Adamczyk-Sowa M, Kułakowska A, et al. Highly active disease and access to disease-modifying treatments in patients with relapsing-remitting multiple sclerosis in Poland. Neurol Neurochir Pol. 2022; 56(3): 256–260.
  20. Leray E, Yaouanq J, Le Page E, et al. Evidence for a two-stage disability progression in multiple sclerosis. Brain. 2010; 133(Pt 7): 1900–1913.
  21. Lebrun C, Cohen M, Clavelou P, et al. SFSEP. Evaluation of quality of life and fatigue in radiologically isolated syndrome. Rev Neurol (Paris). 2016; 172(6-7): 392–395.
  22. Berger JR, Pocoski J, Preblick R, et al. Fatigue heralding multiple sclerosis. Mult Scler. 2013; 19(11): 1526–1532.
  23. Disanto G, Zecca C, MacLachlan S, et al. Prodromal symptoms of multiple sclerosis in primary care. Ann Neurol. 2018; 83(6): 1162–1173.
  24. Feinstein A, DeLuca J, Baune BT, et al. Cognitive and neuropsychiatric disease manifestations in MS. Mult Scler Relat Disord. 2013; 2(1): 4–12.
  25. Amato MP, Hakiki B, Goretti B, et al. Italian RIS/MS Study Group. Association of MRI metrics and cognitive impairment in radiologically isolated syndromes. Neurology. 2012; 78(5): 309–314.
  26. Pokryszko-Dragan A, Nowakowska-Kotas M, Ciastoń R, et al. Vocational activity for patients with multiple sclerosis. Neurol Neurochir Pol. 2022; 56(5): 435–440.
  27. Cortese M, Riise T, Bjørnevik K, et al. Preclinical disease activity in multiple sclerosis: A prospective study of cognitive performance prior to first symptom. Ann Neurol. 2016; 80(4): 616–624.
  28. Vienažindytė I, Cesarskaja J, Vaičiulytė D, et al. Do prodrome symptoms influence multiple sclerosis disease course and severity? Medical Hypotheses. 2022; 165: 110888.
  29. Lewer D, O'Reilly C, Mojtabai R, et al. Antidepressant use in 27 European countries: associations with sociodemographic, cultural and economic factors. Br J Psychiatry. 2015; 207(3): 221–226.
  30. Högg T, Wijnands JMA, Kingwell E, et al. Mining healthcare data for markers of the multiple sclerosis prodrome. Mult Scler Relat Disord. 2018; 25: 232–240.
  31. Almeida MN, Silvernale C, Kuo B, et al. Bowel symptoms predate the diagnosis among many patients with multiple sclerosis: A 14-year cohort study. Neurogastroenterol Motil. 2019; 31(6): e13592.
  32. Aharony SM, Lam O, Corcos J. Evaluation of lower urinary tract symptoms in multiple sclerosis patients: Review of the literature and current guidelines. Can Urol Assoc J. 2017; 11(1-2): 61–64.
  33. Zhao Y, Wijnands JMA, Högg T, et al. Interrogation of the multiple sclerosis prodrome using high-dimensional health data. Neuroepidemiology. 2020; 54(2): 140–147.
  34. Chaloulos-Iakovidis P, Wagner F, Weber L, et al. Predicting conversion to multiple sclerosis in patients with radiologically isolated syndrome: a retrospective study. Ther Adv Neurol Disord. 2021; 14: 17562864211030664.
  35. Lebrun-Frénay C, Rollot F, Mondot L, et al. RISC, SFSEP, and OFSEP Investigators. Risk factors and time to clinical symptoms of multiple sclerosis among patients with radiologically isolated syndrome. JAMA Netw Open. 2021; 4(10): e2128271.
  36. Lebrun C, Bensa C, Debouverie M, et al. Club Francophone de la Sclérose en Plaques. Association between clinical conversion to multiple sclerosis in radiologically isolated syndrome and magnetic resonance imaging, cerebrospinal fluid, and visual evoked potential: follow-up of 70 patients. Arch Neurol. 2009; 66(7): 841–846.
  37. Bjornevik K, Munger KL, Cortese M, et al. Serum neurofilament light chain levels in patients with presymptomatic multiple sclerosis. JAMA Neurol. 2020; 77(1): 58–64.
  38. Sapko K, Jamroz-Wiśniewska A, Marciniec M, et al. Biomarkers in Multiple Sclerosis: a review of diagnostic and prognostic factors. Neurol Neurochir Pol. 2020; 54(3): 252–258.

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