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Multiple sclerosis in the elderly: a retrospective cohort study

  • Original Communication
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Abstract

Background

There is a lack of knowledge of disease course, prognosis, comorbidities and potential treatments of elderly MS patients.

Objective

To characterize the disease course including disability progression and relapses, to quantify the use of DMTs and to identify comorbidities and risk factors for progression in elderly multiple sclerosis (MS) patients.

Methods

This is a retrospective study of 1200 Austrian MS patients older than 55 years as of May 1st, 2017 representing roughly one-third of all the MS patients of this age in Austria. Data were collected from 15 MS centers including demographics, first symptom at onset, number of relapses, evolvement of disability, medication, and comorbidities.

Results

Median observation time was 17.1 years with 957 (80%) relapsing and 243 (20%) progressive onsets. Average age at diagnosis was 45 years with a female predominance of 71%. Three-hundred and twenty-six (27%) patients were never treated with a DMT, while most treated patients received interferons (496; 41%) at some point. At last follow-up, 420 (35%) patients were still treated with a DMT. No difference was found between treated and never-treated patients in terms of clinical outcome; however, patients with worse disability progression had significantly more DMT switches. Pyramidal onset, number of comorbidities, dementia, epilepsy, and psychiatric conditions as well as a higher number of relapses were associated with worse outcome. The risk of reaching EDSS 6 rose with every additional comorbidity by 22%. In late and very-late-onset MS (LOMS, VLOMS) time to diagnosis took nearly twice the time compared to adult and early onset (AEOMS). The overall annualized relapse rate (ARR) decreased over time and patients with AEOMS had significantly higher ARR compared to LOMS and VLOMS. Four percent of MS patients had five medications or more fulfilling criteria of polypharmacy and 20% of psychiatric drugs were administered without a matching diagnosis.

Conclusions

In this study, we identified number of comorbidities, pyramidal and cerebellar signs, and a higher number of relapses as unfavorable prognostic factors in elderly MS patients filling gaps of knowledge in patients usually underrepresented in clinical trials and may guide future therapeutic studies.

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Data Availability

Data supporting the findings of this study are available from the corresponding author upon reasonable request by a qualified researcher.

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Acknowledgements

This study was supported by Sanofi Austria.

Author information

Authors and Affiliations

  1. Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria

    Anne Zinganell, Klaus Berek, Barbara Hofer, Michael Auer, Harald Hegen, Franziska Di Pauli & Florian Deisenhammer

  2. Department of Medical Statistics, Informatics and Health Economics, Medical University Innsbruck, Innsbruck, Austria

    Georg Göbel

  3. Department of Neurology, Hospital of Mauer Amstetten, Mauer, Austria

    Susanne Asenbaum-Nan

  4. Department of Neurology, Hospital of St. Pölten, St. Pölten, Austria

    Matin Barang

  5. Department of Neurology, Kepler Universitätsklinikum, Linz, Austria

    Klaus Böck, Stephan Eger & Christian Eggers

  6. Neurologist, Salzburg, Austria

    Christian Bsteh

  7. Department of Neurology, Medical University of Vienna, Vienna, Austria

    Gabriel Bsteh & Barbara Kornek

  8. Department of Neurology, Klinik Landstrasse, Vienna, Austria

    Elisabeth Fertl & Damir Joldic

  9. Department of Neurology, Medical University of Graz, Graz, Austria

    Michael Khalil

  10. Department of Neurology, Hospital of Rankweil, Rankweil, Austria

    Dieter Langenscheidt

  11. Department of Neurology, Hospital of Klagenfurt, Klagenfurt, Austria

    Martina Komposch

  12. Neurologist, Zell Am See, Austria

    Jörg Kraus

  13. Department of Laboratory Medicine, Paracelsus Medical University and Salzburger Landeskliniken, Salzburg, Austria

    Jörg Kraus

  14. Department of Neurology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany

    Jörg Kraus

  15. Department of Neurology, Hospital of Villach, Villach, Austria

    Reinhard Krendl

  16. Department of Neurology, Klinik Donaustadt, Vienna, Austria

    Helmut Rauschka

  17. Karl Landsteiner Institute for Neuroimmunological and Neurodegenerative Disorders, Department of Neurology, Klinik Donaustadt, Vienna, Austria

    Helmut Rauschka

  18. Department of Neurology, Landesklinikum Mistelbach, Mistelbach, Austria

    Johann Sellner

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  1. Anne Zinganell
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  2. Georg Göbel
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Corresponding author

Correspondence to Florian Deisenhammer.

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AZ has participated in meetings sponsored by, received speaking honoraria or travel funding from Biogen, Merck, Novartis, Sanofi-Genzyme and Teva. GG has nothing to disclose. KB has participated in meetings sponsored by and received travel funding from Roche and Biogen. BH has nothing to disclose. SA-N participated in meetings sponsored by and received travel grants from Biogen, Genzyme-Sanofi, Janssen, Merck, Novartis Pharma, Pfizer, Roche and Teva. MB participated in meetings sponsored by and received travel grants from Novartis, Janssen, Celgene and Shire. TB has participated in meetings sponsored by and received honoraria (lectures, advisory boards, consultations) from pharmaceutical companies marketing treatments for MS: Allergan, Bayer, Biogen, Bionorica, Celgene/BMS, GSK, GW/Jazz Pharma, Horizon, Janssen-Cilag, MedDay, Merck, Novartis, Octapharma, Roche, Sandoz, Sanofi-Genzyme, and Teva. His institution has received financial support in the past 12 months by unrestricted research grants (Bayer, Biogen, Celgene/BMS, Merck, Novartis, Sanofi Aventis, and Teva) and for participation in clinical trials in multiple sclerosis sponsored by Alexion, Bayer, Biogen, Celgene/BMS, Merck, Novartis, Octapharma, Roche, Sanofi-Genzyme, and Teva. KB has nothing to disclose. CB has participated in meetings sponsored by or received travel funding by: Celgene, Janssen/Johnson Johnson, Lilly, Merck, Novartis, Roche, and Sanofi/Genzyme. GB has participated in meetings sponsored by, received speaker honoraria or travel funding from Biogen, Celgene-BMS, Lilly, Merck, Novartis, Sanofi-Genzyme and Teva, and received honoraria for consulting Biogen, Celgene-BMS, Merck, Novartis, Roche, Sanofi-Genzyme and Teva. SE has nothing to disclose. CE received honoraria for participation in advisory boards from Biogen, Genzyme-Sanofi, Gilead, Merck, Novartis, Roche, and Teva Ratiopharm; speakers honoraria from Merck, Genzyme-Sanofi, Teva Ratiopharm, Roche, Biogen, Novartis; and honoraria for conducting clinical GCP trials from Merck, Teva Ratiopharm, Roche, and Genzyme-Sanofi. EF has received honoraria for presentations or consulting from Almirall, BMS, Biogen, Böhringer, Janssen, Merck, Novartis and Roche. DJ has participated in meetings sponsored by, received speaking honoraria or travel funding from Almirall, Biogen, Merck, Novartis, Sanofi and Roche. MK has received funding for travel and speaker honoraria from Bayer, Novartis, Merck, Biogen Idec and Teva Pharmaceutical Industries Ltd. and serves on scientific advisory boards for Biogen Idec, Merck Serono, Roche, Novartis and Gilead. DL has received honoraria from Biogen, Novartis, Merck, and Roche. MK has participated in meetings sponsored by or travel funding from Novartis, Roche, Biogen, Merck, Sanofi-Genzyme and Teva. BK has received honoraria for speaking and/or consulting from Biogen, BMS Celgene, Johnson&Johnson, Merck, Novartis, Roche, Sanofi-Genzyme, and Teva. JK has received honoraria for speaking and/or consulting from Abbvie, Almirall, Biogen, BMS Celgene, Cannaxan, Grünenthal, Johnson&Johnson, Lilly, Merck, Novartis, Pharmgenetix, Roche, Sandoz, Sanofi-Genzyme, and Teva. RK has nothing to disclose. HR has participated in meetings sponsored by, or received honoraria for acting as an advisor/speaker from Alexion, Biogen, Genzyme-Sanofi, Merck and Novartis. JS received honoraria for presentations from Alexion, Angelini, BMS, Biogen, Boehringer, Janssen, Novartis, Roche, Pfizer, Roche, Sandoz and Sanofi. He serves on scientific advisory boards of Alexion, BMS, Biogen, Boehringer, Novartis, Roche, Sandoz and Sanofi. He is a medical monitor for a clinical trial of Immunic. MA received speaker honoraria and/or travel grants from Biogen, Merck, Novartis and Sanofi. HH has participated in meetings sponsored by, received speaker honoraria or travel funding from Bayer, Biogen, Celgene, Merck, Novartis, Sanofi-Genzyme, Siemens, Teva, and received honoraria for acting as consultant for Biogen, Celgene, Novartis and Teva. FDP has participated in meetings sponsored by, received honoraria (lectures, advisory boards, and consultations) or travel funding from Bayer, Biogen, Janssen-Cilag, Merck, Novartis, Sanofi-Genzyme, Teva, Celgene and Roche. Her institution has received research grants from Roche. FD has participated in meetings sponsored by or received honoraria for acting as an advisor/speaker for Alexion, Almirall, Biogen, Celgene, Genzyme-Sanofi, Janssen, Merck, Novartis Pharma, and Roche. His institution has received research grants from Biogen and Genzyme-Sanofi. He is the section editor of the MSARD Journal (Multiple Sclerosis and Related Disorders) and review editor of Frontiers in Neurology.

Ethical standard statement

The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of the Medical University of Innsbruck (1160/2017). As this was a retrospective study, the ethics committee did not require written informed consent from study participants.

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Appendices

Appendix

Contributing centers

n (%)

Medical University of Innsbruck

254 (21.2)

Medical University of Graz

123 (10.3)

Neuromedcampus Linz

106 (8.8)

Klinik Landstraße

105 (8.8)

Klinikum Klagenfurt

101 (8.4)

Medical University of Salzburg

101 (8.4)

KUK Linz

61 (5.1)

Landesklinikum St. Pölten

59 (4.9)

Landeskrankenhaus Villach

58 (4.8)

Medical University of Vienna

55 (4.6)

Barmherzige Brüder Linz

52 (4.3)

SMZ Ost Vienna

51 (4.3)

Landesklinikum Mauer Amstetten

43 (3.6)

Landeskrankenhaus Rankweil

15 (1.3)

Dr. Jörg Kraus

12 (1)

Dr. Christian Bsteh

4 (0.3)

 

1200 (100)

Comorbidities

Psychiatric, n = 400, 33.3%

Addiction, adjustment disorder, affective disorder, anxiety, bipolar disorder, bulimia, delusional disorder, depression, organic brain disease, panic disorder, psychosis, and somatic symptom disorder.

Cardiovascular diseases and risk factors, n = 623, 52%

Arterial hypertonia, atherosclerosis, cardiac arrhythmia, congestive heart failure, coronary heart disease, diabetes mellitus, hyperlipidemia, myocardial infarction, obesity, peripheral vascular disease, stroke, Tako-Tsubo cardiomyopathy, transient ischemic attack, and valvular disease.

Cancer, n = 111, 9.3%

Bladder cancer, breast cancer, cervical cancer, colorectal cancer, duodenal cancer, endometrial cancer, esophageal cancer, gastric carcinoma, laryngeal cancer, lung cancer, lymphoma, melanoma, multiple myeloma, oral cancer, ovarian cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, squamous cell carcinoma, testicular cancer, thyroid cancer, and urothelial carcinoma.

Dementia, n = 33, 2.8%

Alzheimer’s disease, mild cognitive impairment, Parkinson’s disease—dementia, subcortical dementia, and vascular dementia.

Epilepsy, n = 51, 4.3%

Absence-epilepsy, focal epilepsy, generalized epilepsy, symptomatic epilepsy, and temporal lobe epilepsy.

Female genital system, n = 99, 8.3%

Endometriosis, hysterectomy, oophorectomy, ovarian cyst, and uterine fibroid.

Gastrointestinal, n = 117, 9.8%

Appendectomy, cholecystectomy, cholelithiasis, chronic hepatitis, coeliac disease, Crohn’s disease, diverticulosis, gastritis, hepatic steatosis, ileus, inflammatory bowel disease, pancreatitis, peritonitis, primary biliary cholangitis, toxic megacolon, and ulcerative colitis.

Headache, n = 63, 5.3%

Migraine, tension headache, and trigeminal neuralgia.

Infectious disease, n = 10, 0.8%

Hepatitis B, hepatitis C, and hepatitis E.

Kidney / bladder, n = 85, 7.1%

Angiomyolipoma, benign prostatic hyperplasia, chronic urinary tract infection, cirrhotic kidney, cystocele, hydronephrosis, kidney failure, micturition disturbance, nephrectomy, nephrolithiasis, pyelonephritis, renal artery stenosis, renal bypass, renal cell carcinoma, renal cysts, and renal insufficiency.

Lung disease, n = 65, 5.4%

Allergic alveolitis, asthma, chronic obstructive pulmonary disease, chronic pneumonia, lobectomy, pulmonary embolism, pulmonary emphysema, and pulmonary hypertension.

Osteoporosis, n = 158, 13.2%

Osteoporosis.

Polyneuropathy, 28, 2.3%

Axonal polyneuropathy, chronic inflammatory demyelinating polyneuropathy, critical illness polyneuropathy, diabetic polyneuropathy, and sensomotoric polyneuropathy.

Rheumatoid arthritis, n = 8, 0.7%

Psoriasis arthritis and rheumatoid arthritis.

Skin disease, n = 48, 4%

Actinic cheilitis, alopecia areata, common wart, decubitus, erythema nodosum, leukocytoclastic vasculitis, pityriasis, psoriasis, Raynaud’s phenomenon, scleroderma, seborrheic dermatitis, systemic lupus erythematosus, ulceration, urticaria, and varicose.

Thyroid disease, n = 267, 22.3%

Autoimmune thyroid disease, Hashimoto thyroiditis, hyperthyroidism, hypothyroidism, nodular goiter, thyroid adenoma, and thyroidectomy.

Visual disorders, n = 79, 6.6%

Amaurosis, cataract, glaucoma, open-angle-glaucoma, macular degeneration, posterior vitreous detachment, retinal detachment, retinal vasculitis, and sicca syndrome.

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Zinganell, A., Göbel, G., Berek, K. et al. Multiple sclerosis in the elderly: a retrospective cohort study. J Neurol 271, 674–687 (2024). https://doi.org/10.1007/s00415-023-12041-1

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