Journal Volume 6 - March 2012
Association between Low Vitamin D Levels and Recurrent Inflammatory Spinal Cord Disease
Research Team: Maureen A. Mealy, RN, BSN; Scott Newsome, DO; Benjamin M. Greenberg, MD, MHS; Dean Wingerchuk, MD, MSc; Peter Calabresi, MD; Michael Levy, MD, PhD
This study was first published online in the Archives of Neurology on 14 November 2011.
This summary was prepared by Mary Coakley, a member of the TMA.
Previous studies involving patients with multiple sclerosis have established a link between low vitamin D levels and both increased risk of developing multiple sclerosis (MS) and higher relapse rates in those already diagnosed with MS. The objective of this study was to look at the association between low vitamin D levels and the recurrence rate of inflammatory spinal cord disease, in order to see whether vitamin D might play a role in preventing a single inflammatory attack of the spinal cord from developing into a recurrent disease.
Recently there has been a lot of interest in the role of vitamin D in a number of autoimmune diseases including MS. Previous studies involving patients with MS have established a link between low vitamin D levels with both increased risk of developing MS, and higher relapse rates in those already diagnosed.
Patients with NMO are more likely to have a recurrent rather than monophasic disease. A specific antibody marker is closely associated with NMO; 99% of patients who have this marker, and who already have a spinal cord or optic nerve disease, will go on to develop NMO.
It is not known why some patients have a monophasic attack of inflammatory spinal cord disease, while others have recurrent disease. Earlier studies showed that TM patients have higher than normal levels of certain proteins that are known to trigger inflammatory attacks as well as suppress immune reactions. Supplementation with vitamin D has been shown to reduce levels of these proteins. While there are likely to be a number of differences between patients who have monophasic vs. recurrent inflammatory spinal cord disease, we wanted to see if there was a marked difference in vitamin D levels between the two groups.
This study involved a retrospective analysis of 77 patients who were seen at the Johns Hopkins Transverse Myelitis Center over a period of six years. Data recorded included: age, race, sex, zip code, season, diagnosis, mobility and status of NMO-IgG (antibodies associated with NMO). Three different laboratories were used in the vitamin D testing. We found no major difference in the average vitamin D level when grouped by testing laboratory. We excluded any patients who were taking more than 800 IU of Vitamin D as a supplement at the time of the draw. We also excluded any patients who's time of onset of the disease, to the first vitamin D test, was more than 25 years.
We divided the patients into two groups—a monophasic group and a recurrent group. For the monophasic group, all of the patients had been diagnosed with idiopathic transverse myelitis (ITM). They had all been checked for any underlying cause for their initial TM attack. Patients were excluded from this group if there was an indication of: any infectious cause, prior spinal cord inflammation or demyelination, or a diagnosis of MS or rheumatologic disease. We also required that any patients included in the study, had to have been followed for at least a year after their initial attack, and that they were disease-free during the onset of their attack, not using any drugs to modify or suppress their immune system. The recurrent group included patients with recurrent TM/NMO/NMO spectrum disorders. A few patients included in the study also had a rheumatologic disease. For example, four patients had lupus and one had Sjögren syndrome.
Using statistical analyses, we compared the two groups. Adjustments were made for differences in age, race, sex, and season at the time of the vitamin D test. We compared vitamin D levels and mobility. Because African Americans usually have much lower vitamin D levels than non-Hispanic whites, we did a separate analysis where we excluded the African American patients. The sample size was too small to allow us to adjust for latitude.
The study involved a total of 77 patients; there were 44 patients in the monophasic group and 33 patients in the recurrent group. The two groups were alike in a number of respects. The median age was 46.5 in the monophasic group, and 48 in the recurrent group. The degree of mobility was also similar between the two groups, as was the time of year when the vitamin D levels were tested. The mean time from the initial attack to the first blood draw was slightly longer in the recurrent group than in the monophasic group.
There was a marked difference in Vitamin D levels between the two groups. In the monophasic group the mean level was 33 ng/mL, while in the recurrent group the mean level was 18 ng/mL. This put the mean vitamin D level of the recurrent group in the deficient range.
There were two major demographic differences between the two groups. Women made up slightly more than half of the monophasic group, but accounted for almost three-quarters of the recurrent group. African Americans were also over-represented in the recurrent group, with16 of the 18 African American patients in the study having recurrent disease, compared to 14 of the 54 white patients. Because of this, and since race is a well-known factor affecting vitamin D levels, we excluded the African American patients before doing a separate analysis. Even in the separate analysis there was still a significant difference between the vitamin D levels in the two groups.
We also looked at mobility status, but did not find a significant difference in mean vitamin D levels across the four mobility/disability groups. We noticed a slight decrease in vitamin D levels with time elapsed since blood draw. There was a much more significant decrease in vitamin D levels with age. We did account for age in doing our statistical analysis.
Our study suggests there may be a link between low vitamin D levels and recurrent inflammatory spinal cord disease. This is consistent with what has been found in other recurrent autoimmune disorders. This suggests an association between immune function and vitamin D. This suggests that low vitamin D may contribute to the onset and recurrence of autoimmune disorders such as TM and NMO.
Because this study was retrospective, there were some variables that we couldn't control, e.g., forms of vitamin D (D3 vs. D2), body mass index, and daily sun exposure. Also there were differences in when vitamin D was tested; in some cases testing was done within months of onset of the disease, but in some cases it was many years later. Additionally, some patients had the test done on a routine doctor's visit, while in other cases it was done while the patient was having an inflammatory event. It is not known whether the disease can influence vitamin D levels or vice versa.
In conclusion, the study showed that vitamin D levels were much lower in patients who developed recurrent spinal cord disease than in those who were diagnosed with monophasic disease. More studies are needed to investigate this topic further and also to see if vitamin D supplementation can reduce the frequency of repeat attacks.