Daily News for Neuros, Nurses & Savvy MSers: 208,152 Viewers, 8,368 Stories & Studies
Click Here For My Videos, Advice, Tips, Studies and Trials.
Timothy L. Vollmer, MD
Department of Neurology
University of Colorado Health Sciences Center Professor

Co-Director of the RMMSC at Anschutz Medical Center

Medical Director-Rocky Mountain MS Center
Click here to read my columns
Brian R. Apatoff, MD, PhD
Multiple Sclerosis Institute
Center for Neurological Disorders

Associate Professor Neurology and Neuroscience,

Weill Medical College of Cornell University

Clinical Attending in Neurology,
New York-Presbyterian Hospital
You'll get FREE Breaking News Alerts on new MS treatments as they are approved

HERE'S A FEW OF OUR 6000+ Facebook & MySpace FRIENDS
Timothy L. Vollmer M.D.
Department of Neurology
University of Colorado Health Sciences Center
Co-Director of the RMMSC at Anschutz Medical Center
Medical Director-Rocky Mountain MS Center

Click to view 1280 MS Walk photos!

"MS Can Not
Rob You of Joy"
"I'm an Mom has MS and we have a message for everyone."
- Jennifer Hartmark-Hill MD
Beverly Dean

"I've had MS for 2 years...this is the most important advice you'll ever hear."
"This is how I give myself a painless injection."
Heather Johnson

"A helpful tip for newly diagnosed MS patients."
"Important advice on choosing MS medication "
Joyce Moore

This page is powered by Blogger. Isn't yours?



Surgery and Risk for Multiple Sclerosis: A Systematic Review and Meta-analysis of Case-Control Studies

Surgery and Risk for Multiple Sclerosis
A Systematic Review and Meta-analysis of Case-Control Studies

Abstract-Background: Although the precise etiology of multiple sclerosis is largely unknown, there is some speculation that a prior history of surgery may be associated with the subsequent risk for developing the disease. Therefore, we aimed to examine surgery as a risk factor for the diagnosis of multiple sclerosis.
We found a small but statistically significant and clinically important increased risk for developing multiple sclerosis, in those with tonsillectomy and appendectomy at ≤ 20 years of age. There was no convincing evidence to support the association of other surgeries and the risk for multiple sclerosis. Well-designed prospective etiological studies, pertaining to the risk for developing multiple sclerosis, ought to be conducted and should include the examination of various surgeries as risk factors.

We searched for observational studies that evaluated the risk for developing multiple sclerosis after surgery that occurred in childhood (≤ 20 years of age) or "premorbid" (> 20 years of age). We specifically included surgeries classified as: tonsillectomy, appendectomy, adenoidectomy, or "surgery". We performed a systematic review and meta-analyses and calculated odds ratios (OR) and their 95% confidence intervals (CIs) using a random effects model.

Description of the Condition
The first symptoms or signs of MS, diagnosed by a physician, are referred to as the clinical onset of the disease. As there are limited (and consistent) clinical, laboratory, and imaging findings in MS, diagnostic classifications are generally reduced to "definite MS" and "possible MS". Several established diagnostic standards have been used over the years to assist physicians in the diagnosis of MS; these include criterion such as the Poser criteria[3] and most recently the McDonald criteria.[4]
Although the precise etiology of MS is largely unknown, epidemiological studies point at an important role in both genetic and environmental factors that seem to act synergistically increasing an individual's risk of developing the disease. Specifically, risks such as genetic factors (the presence of HLA-DRB1*15 alleles), infectious causes including Epstein-Barr virus (EBV), vitamin D insufficiency, exposure to cigarette smoke, and a more northern geographic residence (latitude) have all been well documented in the literature.[5–9] There is some speculation that other factors, including a history of tonsillectomy, appendectomy, or other surgery may also be associated with the risk of developing MS.[10]

Overall, the evidence presented in this review supports a relationship between tonsillectomy and appendectomy in childhood and the subsequent risk of MS. More specifically, those with tonsillectomy or appendectomy at ≤ 20 years of age were approximately 30% more likely to be diagnosed with MS in comparison to similar patients who did not have a tonsillectomy or appendectomy at ≤ 20 years of age. The findings of this review do not support an association between tonsillectomy or appendectomy occurring in those > 20 years, adenoidectomy, and "other surgery" occurring at any age and the subsequent risk for the onset of MS. Although we did not find an association between these variables and risk for MS, it is important to note that due to the multi-factorial and heterogeneous nature of MS, surgery may indeed pose a slight risk for certain individuals.

Several theories linking tonsillectomy to MS risk have been postulated over the years. Meurman and Wising[39] proposed tonsillectecomy as a possible risk factor for MS in that an upper respiratory tract infection may trigger MS or that a locally deficient immune system may facilitate the invasion of an etiologically relevant, infectious agents. Tonsillectomy may leave sufficient lymphoid tissue adjacent to the central nervous system to instigate the exaggerated immune response seen in MS.[39,69,87] Poskanzer (1965) was particulary interested in examining tonsillectomy and MS risk at it predisposes to the development of neurological complications in poliomyelitis, another infection that is much more widespread than is suggested by its neurological manifestations.[87,97–99]

Of particular interest is the association between recurrent tonsillitis and EBV infection and reactivation.[100] A recent meta-analysis of case–control and cohort studies found a statistically significant combined relative risk (RR) for MS in those with a past history of infectious mononucleosis (RR = 2.17; 95% CI, 1.97–2.39).[101] Furthermore, others have found statistically significant elevated levels of antibody to some common infectious agents, other than EBV, in children and adults with MS compared to controls.[92,102–104] Krone and collegues[104] postulate that these findings reflect a dysregulation of immune function as a consequence of the development of the disease. They assert that immune dysregulation in MS is likely to be an early event preceding the onset of MS disease by many years or even decades.[14,105,106] It is likely that the elevated antibody concentrations do not directly cause MS but rather reflect a shift in patterns of immune reactivity away from protection towards enhancement of the risk of disease. These authors suggest that studies on MS-associated infectious agents could lead to the identification of specific antigenic determinants involved in the generation and maintenance of immune dysregulation.

There seems to be similarities between MS and appendicitis, which often results in appendectomy. More recently, scientists have recognized the role of the appendix as part of the body's immune system, as it contains white blood cells and acts as a reservoir for "good" bacteria for the gut
.[107] The role of the appendix is to contain "good bacteria"; when bacteria in the intestines die or are purged from dysentery or cholera, the "good bacteria" are replaced from the stores in the appendix. As a result, appendicitis (inflammation of the appendix) may indicate inadequate immunological function;[84,89,108] thereby providing an association of both EBV and appendicitis (resulting in appendectomy) with MS.[109–111] Immunological reaction relevant to appendicitis may indicate MS risk as activation of peripheral blood mononuclear cells, including those causing inflammatory destruction of myelin, which occurs in lymphoid tissue.[89,108] Appendicitis is a marker of immune characteristics influencing immune-mediated disease risk, as it has a direct role in the development of ulcerative colitis.[89,112,113] Further, CD8+ T-cell deficiency is a feature of both ulcerative colitis and MS.[114]

There seems to be other possible similarities between MS and appendicitis. First, appendicitis and MS are autoimmune diseases. Both appendicitis and MS are diseases associated with industrialized countries but not developing countries.[115,116] MS is a disease largely prevalent in Europe, North America, Australia, and New Zealand, but is rare among Asians and Africans.[116] Lastly, several epidemiological and experimental studies support the hygiene hypothesis in both appendicitis[115,117] and MS,[109,118] which postulates that immunopathology may be an unanticipated consequence of advances in sanitation and public health.[109,118,119]


This result of this meta-analysis suggests a statistically significant and clinically important increased risk for developing MS in those with tonsillectomy and appendectomy at ≤ 20 years of age. Despite this significant finding, this in no way suggests or demonstrates causality, in that epidemiological studies can only provide etiological clues at best. More rigorous prospective studies, with high statistical power, are needed to prove an effect. Future prospective studies, that take into consideration the long latency period between the age of putative biological onset and clinical onset of MS, are needed in order to definitively rule out any links between tonsillectomy (or other surgeries) and MS.

Go to Newer News Go to Older News