Multiple Sclerosis (MS)


Patients with multiple sclerosis (MS) appear to be at an increased risk for a number of comorbidities. These comorbidities can potentially lead to a longer time to diagnosis, a decreased likelihood of initiating disease-modifying treatments, and a reduced quality of life for patients.1

Psychiatric Comorbidities

One of the most commonly described multiple sclerosis comorbidities for patients is depression. Estimates of depression prevalence in studies range from as low as 3.8% to as high as 70.1%.2 The definition of depression and the source used to identify it, such as clinical diagnosis versus patient surveys, may account for some of the variability. An extensive review article on psychiatric disorders in MS estimated the rate to be approximately 23.7%.2 The prevalence of depression is generally reported to be 2-3 times higher in patients with MS than in the general population.3 

The etiology of depression in these patients may be due to multifaceted causes. These include activation of hippocampal microglia, regional neural atrophy, a buildup of MS lesions, and other neurological factors, as well as the stress of living with a chronic, progressive disorder.3

Another common psychiatric issue occurring more often in MS patients than in the general population is anxiety. Estimated prevalences in studies also vary considerably, but a systematic review of high-quality studies found an estimated prevalence of anxiety of 21.9%.2

Other psychiatric disorders that have been found to be more prevalent among people with MS include bipolar disorder, alcohol abuse, and schizophrenia.2

Cardiac and Cerebrovascular Comorbidities

Several studies have shown an increased prevalence of cardiovascular comorbidities among MS patients. A review article found that most well-designed studies showed that MS patients had a higher risk of congestive heart failure, ischemic heart disease, stroke, and peripheral vascular disease.4 The authors stated that these increased risks may be due to lifestyle factors such as being overweight or obese, smoking, and a lack of physical activity.

The article also found conflicting results between studies for prevalence compared to the general population for several other cardiac and vascular comorbidities, including hypertension, hyperlipidemia, cardiac arrhythmia, and valvular disorders.4 These studies varied in their time periods, geographic locations, populations studied, and data collection methods, which complicates comparisons.

Autoimmune Disorders

MS and various autoimmune disorders have been reported together in several patient studies, indicating there may be some underlying etiological factors between the diseases. One Danish study found that patients with type 1 diabetes mellitus appear to have a 3-fold increased risk of MS, compared with the general population.5 This was consistent with a more recent case-control Danish study which found an odds ratio of 3.34 (P =0.008) for having type 1 diabetes prior to being diagnosed with MS; however, this ratio was only true for male patients.6 There were no increased odds found in female patients. A study of German and Austrian patients also found an increased risk of MS in type 1 diabetes patients.7

Autoimmune disorders are relatively rare, which can affect estimates of their prevalence and increased risk in patients with MS. Several other autoimmune disorders beyond type 1 diabetes have been reported with varying levels of risk in studies, including psoriasis,8 autoimmune thyroiditis,8 systemic lupus erythematosus,6 and inflammatory bowel diseases, such as Crohn’s disease and ulcerative colitis.9 

Cancer and MS

The link between cancer and MS has been investigated in numerous studies over the years, which have yielded conflicting results. Studies conducted in New York state,10 a university medical center in Italy,11 and a hospital district in Finland12 all found cancer rates in MS patients similar to or below expected values for the general population.

In contrast to these, a large study in Norway found that MS patients had a 14% higher chance of cancer than the general population, with cancers of the respiratory system (66%), urinary system (51%), and central nervous system (52%) carrying the highest risks.13 Finally, a review article found that MS patients had an increased risk of meningioma and urinary system cancers but a decreased risk of prostate, testicular, pancreatic, and ovarian cancer than expected.14

Sleep Disorders

A number of different sleep disorders have been reported in the literature. The most commonly reported disorders include sleep-disordered breathing, restless leg syndrome, insomnia, and periodic limb movement disorders.15 Some of these disorders can be related to other symptoms or disorders, such as insomnia and depression or anxiety, with each potentially increasing the risk of the others. Disease-related central nervous system damage could also be linked to restless leg syndrome,16 sleep-disordered breathing,17 and potentially even narcolepsy18 in rare cases.

Other MS Comorbidities

Several other comorbidities have been reported in MS patients. A study utilizing a self-reported questionnaire of MS patients from countries around the world found that back pain was the highest reported comorbidity, at 36.2% of patients.19 Chronic lung diseases, including asthma and chronic obstructive pulmonary disease, have also been reported in higher numbers of younger MS patients than expected.20 A meta-analysis found that migraines may also be as much as twice as common in MS patients than in the general population.21

Reviewed by Kyle Habet, MD on 7/1/2021

References

  1. Magyari M, Sorensen PS. Comorbidity in multiple sclerosis. Front Neurol. Published online August 21, 2020. doi:10.3389/fneur.2020.00851
  2. Marrie RA, Reingold S, Cohen J, et al. The incidence and prevalence of psychiatric disorders in multiple sclerosis: a systematic review. Mult Scler. 2015;21(3):305-317. doi:10.1177/1352458514564487
  3. Patten SB, Marrie RA, Carta MG. Depression in multiple sclerosis. Int Rev Psychiatry. 2017;29(5):463-472. doi:10.1080/09540261.2017.1322555
  4. Marrie RA, Reider N, Cohen J, et al. A systematic review of the incidence and prevalence of cardiac, cerebrovascular, and peripheral vascular disease in multiple sclerosis. Mult Scler. 2015;21(3):318-331. doi:10.1177/1352458514564485
  5. Nielsen NM, Westergaard T, Frisch M, et al. Type 1 diabetes and multiple sclerosis: a Danish population-based cohort study. Arch Neurol. 2006;63(7):1001-1004. doi:10.1001/archneur.63.7.1001
  6. Magyari M, Koch-Henriksen N, Pfleger CC, Sørensen PS. Gender and autoimmune comorbidity in multiple sclerosis. Mult Scler. 2014;20(9):1244-1251. doi:10.1177/1352458514521515
  7. Bechtold S, Blaschek A, Raile K, et al. Higher relative risk for multiple sclerosis in a pediatric and adolescent diabetic population: analysis from DPV database. Diabetes Care. 2014;37(1):96-101. doi:10.2337/dc13-1414
  8. Dobson R, Giovannoni G. Autoimmune disease in people with multiple sclerosis and their relatives: a systematic review and meta-analysis. J Neurol. 2013;260(5):1272-1285. doi:10.1007/s00415-012-6790-1
  9. Kosmidou M, Katsanos AH, Katsanos KH, et al. Multiple sclerosis and inflammatory bowel diseases: a systematic review and meta-analysis. J Neurol. 2017;264(2):254-259. doi:10.1007/s00415-016-8340-8 
  10. Gaindh D, Kavak KS, Teter B, et al. Decreased risk of cancer in multiple sclerosis patients and analysis of the effect of disease modifying therapies on cancer risk. J Neurol Sci. 2016;370:13-17. doi:10.1016/j.jns.2016.09.005
  11. Ragonese P, Aridon P, Vazzoler G, et al. Association between multiple sclerosis, cancer risk, and immunosuppressant treatment: a cohort study. BMC Neurol. Published online August 8, 2017. doi:10.1186/s12883-017-0932-0
  12. Hongell K, Kurki S, Sumelahti M-L, Soilu-Hänninen M. Risk of cancer among Finnish multiple sclerosis patients. Mult Scler Relat Disord. 2019;35:221-227. doi:10.1016/j.msard.2019.08.005
  13. Grytten N, Myhr K-M, Celius EG, et al. Risk of cancer among multiple sclerosis patients, siblings, and population controls: A prospective cohort study. Mult Scler. 2020;26(12):1569-1580. doi:10.1177/1352458519877244
  14. Marrie RA, Reider N, Cohen J, et al. A systematic review of the incidence and prevalence of cancer in multiple sclerosis. Mult Scler. 2015;21(3):294-304. doi:10.1177/1352458514564489
  15. Foschi M, Rizzo G, Liguori R, et al. Sleep-related disorders and their relationship with MRI findings in multiple sclerosis. Sleep Med. 2019;56:90-97. doi:10.1016/j.sleep.2019.01.010
  16. Sieminski M, Losy J, Partinen M. Restless legs syndrome in multiple sclerosis. Sleep Med Rev. 2015;22:15-22. doi:10.1016/j.smrv.2014.10.002
  17. Abdel Salam OA, Ghonimi NAM, Ismail MH. Risk of obstructive sleep apnea in multiple sclerosis: frequency, clinical and radiological correlates. Mult Scler Relat Disord. 2019;28:184-188. doi:10.1016/j.msard.2018.12.015
  18. Kallweit U, Bassetti CLA, Oberholzer M, et al. Coexisting narcolepsy (with and without cataplexy) and multiple sclerosis: six new cases and a literature review. J Neurol. 2018;265(9):2071-2078. doi:10.1007/s00415-018-8949-x
  19. Marck CH, Neate SL, Taylor KL, Weiland TJ, Jelinek GA. Prevalence of comorbidities, overweight and obesity in an international sample of people with multiple sclerosis and associations with modifiable lifestyle factors. PLoS One. Published online February 5, 2016. doi:10.1371/journal.pone.0148573
  20. Marrie RA, Patten S, Tremlett H, et al. Chronic lung disease and multiple sclerosis: incidence, prevalence, and temporal trends. Mult Scler Relat Disord. 2016;8:86-92. doi:10.1016/j.msard.2016.05.009
  21. Pakpoor J, Handel AE, Giovannoni G, Dobson R, Ramagopalan SV. Meta-analysis of the relationship between multiple sclerosis and migraine. PLoS One. Published online September 14, 2012. doi:10.1371/journal.pone.0045295

Reviewed by Harshi Dhingra, MD, on 7/21/2021.

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