What is the impact of Vitamin D on the complicated course of MS?

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.

MS prevalence map. By AdertOwn work and [1], CC BY-SA 3.0, Link
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.

MRI scan. NIH Image Galley on Flikr. https://www.flickr.com/photos/nihgov/30805879596

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!

Steampunk Time and Space Machine. Don Urban on Flikr. https://www.flickr.com/photos/donpezzano/3230179951

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.

https://pixabay.com/en/syringe-pill-bottle-morphine-small-1884784/

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?‘.

Pandora’s box. Michael Hensman on Flikr. https://www.flickr.com/photos/mycael/3664900435

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.

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Is MS associated with Vitamin D deficiency?

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

Sunshine Falls. Dawn Ellner on Flikr. https://www.flickr.com/photos/naturesdawn/4299041739

Does Vitamin D deficiency worsen MS 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. 

Milk splash experiment. Endre majoros on Flikr. https://www.flickr.com/photos/boneball/24597145866

Should people with MS be on Vitamin D supplementation?

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

Salmon salad nicoise. Keith McDuffee on Flikr. https://www.flickr.com/photos/gudlyf/3609052894

What to do?

This is the million dollar question eloquently posed by a recent editorial in the journal Neurology titled Preventing multiple sclerosis: to (takevitamin D or not to (takevitamin 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!

Vitamin D Pills. Essgee51 on Flikr. https://www.flickr.com/photos/sg51/5224823967

 

Does rituximab really improve IgM anti-MAG neuropathy?

Long-term efficacy of rituximab in IgM anti-myelin-associated glycoprotein neuropathy: RIMAG follow-up study Iancu Ferfoglia R, Guimarães-Costa R, Viala K, et al. J Peripher Nerv Syst 2016; 21:10-14 Abstract Background The Rituximab vs. Placebo in Polyneuropathy Associated With Anti-MAG IgM Monoclonal Gammopathy (RIMAG) study showed no improvement using the inflammatory neuropathy cause and treatment sensory score […]

via Does rituximab really improve IgM anti-MAG neuropathy? — Neurochecklists Updates

Where in the brain do musicogenic seizures arise from?

Localization of musicogenic epilepsy to Heschl’s gyrus and superior temporal plane: case report. Nagahama Y, Kovach CK, Ciliberto M, et al. J Neurosurg 2017; 15:1-8. Abstract Background: Musicogenic epilepsy (ME) is an extremely rare form of the disorder that is provoked by listening to or playing music, and it has been localized to the temporal […]

via Where in the brain do musicogenic seizures arise from? — Neurochecklists Updates

The 19 most unusual symptoms in neurology

The brain, the principal playground of neurologists, is a complex organ. The more we learn about it, the more we have to unlearn our old certainties. The more we study it, the less it seems to reveal of itself. The brain is fascinating enough when it is functioning normally; it is however most intriguing when it […]

via The 19 most unusual symptoms in neurology — Neurochecklists Updates

A few more catchy neurology article titles to start the year

The Neurology Lounge is addicted to journal articles whose titles show that a lot of thought and attention went into constructing them. I have reviewed some of these in my previous blog posts titled The Art of Spinning Catchy Titles, and The Art of Spinning Catchy Neurology Headlines. To keep the tradition alive, here are a few more recent catchy titles.

Journal Entry. Joel Montes de Oca on Flikr. https://www.flickr.com/photos/joelmontes/4762384399

Stoop to conquer: preventing stroke and dementia together

This comes from an editorial in Lancet Neurology urging a joint approach to preventing stroke and dementia, a strategy the author calls ‘the lowest hanging fruit in the fight against these two greatest threats to the brain’. He argues that ‘at the moment, the fruit might be hanging too low for our gaze, and we are wrongly fixated on the distant future of Alzheimer’s disease treatment. We might have to stoop to conquer‘.

By Gavarni – Le voleur, n°95, 27 août 1858, page 265. Reproduction d’une gravure extraite des Toquades de Paul Gavarni, éditées par Gabriel de Gonet, Paris 1858., Public Domain, Link

Romberg’s test no longer stands up

This opinion piece in Practical Neurology takes a stab at the age-old neurological test of sensory impairment. Subject are asked to stand up and try to maintain their balance with their eyes shut. The author asserts that this, the Romberg’s test, ‘lacks essential specificity’, ‘risks physical injury’, and is ‘redundant’. He argues that there are much better, and safer, ways of testing for sensory ataxia. There goes an interesting test!

By Mikhail KonininFlickr: Meerkat / At the zoo / Novosibirsk / Siberia / 24.07.2012, CC BY 2.0, Link

Dacrystic seizures: a cry for help

This is from a case report of a 69-year old man in the journal Neurology. He presented with unusual crying spells which turned out to be dacrystic (crying) seizures. This case is eventually revealed to be a case of….sorry, no spoilers. Click on the link to find out.

HeartBroken-Tears are the Baptism of the Soul. Anil Kumar on Flikr. https://www.flickr.com/photos/87128018@N00/139136870

Game of TOR -the target of rapamycin rules four kingdoms

I am no fan of Game of Thrones, but it is an in-your-face television series which provides the setting for this catchy title. The mechanistic target of rapamycin (mTOR) pathway is underlies the pathology of tuberous sclerosis. It is therefore the target of many therapeutic strategies in the form of mTOR inhibitors. And the 4 kingdoms? You have to read the piece from the New England Journal of Medicine…perhaps after you have watched the TV series!

Stack. Wendy on Flikr. https://www.flickr.com/photos/wenzday01/4332780839

Restless legs syndrome: losing sleep over the placebo response

This editorial, also from Neurology, addresses the disturbing report in the same journal warning of the high placebo response of interventions for restless legs syndrome (RLS). The title couldn’t be more apt. 

By Edvard Munch – The Athenaeum: pic, Public Domain, Link

 


…and some not very catchy titles

Unfortunately many neurology titles are not as catchy as the ones above. Many article titles appear to be half-baked and fall short. Here are a few:

And the prize for the silliest title in neurology must go to this paper in the Journal of Neural Transmission that is simply…unreadable!