The Neurology Lounge

Some general neurologists get away with not having to think too much about multiple sclerosis (MS). This is because they have an ‘MSologist‘ at hand to refer all their patients with ‘demyelination‘. Many general neurologists however care for people with MS because they do not have a ‘fallback guy‘ to do the heavy lifting for them. This therefore makes it imperative for neurologists to keep up with everything about this often disabling and distressing disorder.

The management of MS is however very tricky, and it is challenging to get a grip of it all. This is partly because the clinical course is varied, and the diagnostic process tortuous. The patient first goes through an onerous retinue of tests which include an MRI, a lumbar puncture, evoked potentials, and a shedload of blood tests. This is all in a bid to secure the diagnosis and to exclude all possible MS mimics.

Then comes the head-scratching phase of determining if the patient actually fulfils the diagnostic criteria for MS, or if they just have clinically isolated syndrome (CIS) and radiologically isolated syndrome (RIS). To secure the diagnosis of MS, the neurologist turns to the McDonald criteria which stipulate dissemination in time and place of inflammatory events. As simple as this should be, this is no easy task at all. This is because, at different times, the criteria have meant different things to different people. The guidelines have also gone through several painful, and often confusing, iterations. Indeed the McDonald criteria have only recently been re-revised-to the delight of MSologists but the chagrin of the general neurologist!

Once the diagnosis of relapsing remitting MS (RRMS) is reasonably established, the patient is taken through a guided tour of the ever-expanding available treatment options. These are typically to prevent relapses, but more recently to prevent disease progression as well. People with mild to moderate MS are nudged towards interferons, glatiramer acetate, dimethylfumarate, or terifluonamide. Those with more aggressive disease, on the other hand, are offered a menu of fingolimod, natalizumab, or alemtuzumab. Other newer agents include daclizumab and cladribine. And, just stepping into the arena, there is ocrelizumab for primary progressive (PPMS). Whichever option is chosen, the course of treatment is long, and it is fraught with risks such as infections and immune suppression.

Once the bigger questions have been settled, the neurologist then braces for the ‘minor’ questions her enlightened patients will ask. The easier questions relate to the treatment of symptoms, and some of the most vexing concern the role of Vitamin D deficiency. Such questions include, ‘Is vitamin D deficiency a cause of MS?‘, ‘Do people who are vitamin D deficient experience a worse outcome?‘, and ‘Should patients with MS be on Vitamin D supplementation?‘.

To attempt to resolve these questions I plunged into some of the literature on Vitamin D and MS. And this is like opening Pandora’s box. Here are some of the things I found.

***

Is MS associated with Vitamin D deficiency?

• In a recent study of Finnish women, a high Vitamin D level seems to protect against developing MS.
• Another study shows that neonates with low VitaminD are at a higher risk of developing MS.
• One study argues that vitamin D is protective against MS. 
• One genetic study of single nucleotide polymorphisms (SNIPs) led to the strong conclusion that low Vitamin D is a cause of MS. The technical details are however too complicated for me. 
• It is postulated that Vitamin D protects against MS by modulating the immune system. 
• It is reported that Vitamin D supplementation reduces the antibody response to the Ebstein Barr virus (EBV) in people with MS

It therefore appears that there is an association of vitamin D deficiency with MS, but it is far from certain that this is a causative relationship. One hypothesis is that vitamin D deficiency is the outcome, rather than the cause, of MS. The deficiency presumably results becuase the very active immune system in people with MS mops up the body’s Vitamin D. This so-called reverse causation hypothesis asserts that vitamin D deficiency is a consumptive vitaminopathy. 

Does Vitamin D deficiency worsen MS progression?

• There is some evidence to show that people with more active MS have lower Vitamin D levels than those with more benign disease.
• One paper reported a higher relapse rate in people with low vitamin D.
• It seems that MS subjects with Vitamin D deficiency have greater disability.
• One study suggests that a low vitamin D level predisposes to early conversion to secondary progressive MS.
• Another recent paper concluded that vitamin D deficiency is a predictor of MS disability and progression.
• Another study found that low vitamin D levels predict new brain MRI lesions. 
• Some studies have however found no association between vitamin D deficiency and MS disability or disability progression.

There is therefore no single answer to this question, but the emerging consensus is that Vitamin D deficiency adversely affects the course of MS. 

Should people with MS be on Vitamin D supplementation?

• A recent paper reports that vitamin D supplementation reduces MS relapses by about 50%.
• Another study reports that vitamin D supplementation reduced relapses in people with MS on natalizumab. 
• On the strength of the evidence, a recent update recommends Vitamin D supplementation for all people with MS. 

Even if Vitamin D deficiency doesn’t cause MS, the evidence suggests that it negatively influences the course of the disease.

What to do?

This is the million dollar question eloquently posed by a recent editorial in the journal Neurology titled Preventing multiple sclerosis: to (take) vitamin D or not to (take) vitamin D? The reasonable consensus is to encourage vitamin D replenishment to prevent MS, starting from preconception. It is also generally agreed that people with MS should be on vitamin D supplementation in the expectation that it will slow the disease activity.

A practical approach to Vitamin D replacement is the Barts MS team vitamin D supplementation recommendation. This is to start with 5,000IU/day vitamin D, and aim for a plasma level of 100-250 nmol/L. Depending on the level, the dose is then adjusted, up or down, to between 2-10,000IU/day. They also advise against giving calcium supplementation unless there is associated osteoporosis.

What is a general neurologist to do? To follow the prevailing trend, and hope it doesn’t change direction too soon!