Researchers are testing a “radical new theory that multiple sclerosis (MS) is caused by blockages in the veins that drain the brain”, BBC News reported.
This theory was tested in 65 people with MS and several different groups of people without MS (controls). The study found that the blood drainage from the brain and spinal cord in people with MS was reduced compared to people without the condition.
However, as these people already had MS at the beginning of the study, it is difficult to say whether the abnormal drainage was a cause of MS or occurred as a consequence of the disease. A much larger sample of people representing each of the four possible types of MS (disease courses) would need to be examined to confirm the findings.
This is a valuable study, but more research is needed. Any implications for the widespread treatment or prevention of MS are some way off.
Where did the story come from?
The research was carried out by Dr Paolo Zamboni and colleagues from the University of Ferrara, Italy. It was funded by the Italian Ministry for University and Scientific Research and by the Foundation Cassa di Risparmio di Ferrara. The study was published in the peer-reviewed Journal of Neurology, Neurosurgery and Psychiatry.
BBC News has reported this research well. However, it did not discuss the main limitation, that researchers cannot known whether abnormal blood drainage is a cause or a consequence of MS.
What kind of research was this?
In this cross sectional study, the researchers examined the drainage of blood from the brain (venous outflow) in people with and without MS. Those without MS included healthy subjects and people with neurological conditions other than MS. Previous post-mortems of people with MS have noted that lesions typical of the disease lie in close proximity to the venous system of the brain.
The difficulty with this study design is that it cannot determine causation. It may have been able to demonstrate that the current venous outflow from the brain was impeded in people with MS. However, it cannot establish whether this preceded the development of MS, or whether the physiological changes in the brain as a result of MS caused the current venous flow.
What did the research involve?
The study included 65 people diagnosed with MS, who were at various stages/courses of the disease, and 235 control subjects without MS. The controls included 60 healthy people matched by age and sex to the MS group. It also included 82 people who were older than the typical age at which MS develops and who were now unlikely to develop it. The reason for including this older group was that if they had venous abnormalities similar to people with MS, it was less likely that these abnormalities were a cause of the condition.
Other controls included 45 people with neurological diseases other than MS (such as Parkinson’s disease and stroke) and 48 people without neurological disease but who were scheduled for venous examination (venography) for other disease indications. People with diseases that are associated with vascular malformations were excluded from the control group.
Venous drainage of the brain and spinal cord was examined using an ultrasound technique (Doppler). Selected patients also had the blood pressure in their jugular veins measured (the large venous system draining blood from the head).
Although the researchers included controls who were past the normal age of MS development to try to ensure that any venous abnormalities among the cases could be more reliably associated with MS, it is difficult to say whether any abnormalities in the MS group were the cause of MS development, rather than a consequence of the disease.
Another drawback is the small number of people with MS examined. A more reliable way of determining that MS is associated with venous outflow abnormalities from the brain would be to assess a much larger sample.
What were the basic results?
People with MS were significantly more likely to have abnormalities in venous drainage from the brain and spinal cord. Further assessment also revealed that, compared to all controls, people with MS had narrowing of the veins draining these areas. This condition is called “cerebrospinal venous insufficiency”. The venous pressure across the narrowed veins was found to be slightly higher than normal for people with MS.
The researchers also note that venous drainage differed between people at different stages and courses of MS (for example, those with relapsing-remitting or secondary progressive courses had different venous abnormalities from those with primary progressive courses). The venous pressure across the narrowed veins was found to be slightly higher than normal.
How did the researchers interpret the results?
The authors conclude that multiple sclerosis is strongly associated with cerebrospinal venous insufficiency, which is characterised by abnormal bloodflow and multiple venous narrowings (strictures) of unknown origin.
This is valuable research that builds on what is known about the physiological changes that occur in the venous system draining the brain and spinal cord in people with MS. The findings also indicate that there are differences in the venous abnormities in people with the four different disease courses of MS. This suggests that the venous obstruction and its location may have a role in determining the clinical course of MS.
The two principal limitations of these findings are:
- The venous abnormalities were examined at one point in time in people who already had clinical MS. As such, it is not possible to say whether these abnormalities are a cause of MS or are part of the physiological changes in the central nervous venous system that result from MS. It is also possible, as the researchers suggest, that the venous changes could be a side effect of the drugs used in MS.
- The study involved a relatively small number of people with MS (and, therefore, even smaller numbers of people with each disease course). To establish a firmer association between MS and cerebrospinal venous insufficiency, and how this differs in each disease course, larger samples need to be examined.
Although this study has found an association between MS and abnormalities in venous drainage from the brain and spinal cord, it is unclear whether these are a cause or a consequence of disease. More research is needed.
Links to the headlines
Multiple sclerosis ‘blood blockage theory’ tested. BBC News, November 27 2009
Links to the science
Zamboni P, Galeotti R, Menegatti E, et al. Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 2009; 80: 392-399