During this week's Multiple Sclerosis (MS) awareness week, Dr Hadi Manji, Consultant Neurologist here at The Physicians' Clinic, provides us with an update.
Multiple Sclerosis is the most common cause of neurological disability in young adults. In the UK, approximately 90,000 individuals are living with the disease.
MS is an inflammatory disorder which is defined by episodes of inflammation affecting the central nervous system (CNS) in different places and at different times. It is relatively rare before puberty and after the age of 60 years. Females are affected more than men in a ratio of 2 to 1.
In the early stages, the immune system (which is there to protect the body from external attack by, for example, infections) is triggered by, as yet, unknown mechanisms to attack myelin which is the fatty sheath around nerves resulting in an episode of 'demyelination'. This may present with loss of vision in one eye (optic neuritis), double vision, weakness, tingling or pins and needles in the limbs or incoordination. Repeated attacks eventually result in loss of the nerve cells or axons and a patient will develop increasing disability.
At onset, 85% of patients will have relapsing remitting MS. After a variable number of years, although the numbers of relapses diminishes, disability progresses – the so-called secondary phase. About 10% of individuals develop progressive disability without relapses – the primary progressive form of MS.
In the last few years, there has been significant progress in our understanding of the underlying disease process and also treatment options. There has been a change of mind-set amongst neurologists who previously may have been rather nihilistic about the benefits of the previously available treatments. A more aggressive attitude is emerging with the belief, though not absolutely proven, that early treatment during the early relapsing remitting phase of the disease may be useful in slowing or preventing the secondary phase for which there is no treatment to date. The goal now is increasingly to reach a point of no evidence of disease activity (NEDA) either clinically or on serial MRI scans.
The Beta interferon group of drugs (interferon beta 1a and beta 1b), have been available since 2002. They reduce the number of relapses by 30%. The drawback is that they have to be injected under the skin or into muscle. Another drug, glatiramer acetate, which works by a different mechanism, has similar effects as the interferons. It also has to be injected three times a week.
Since 2014, two oral drugs have been approved for active relapsing remitting MS – teriflunomide (taken once a day) and dimethyl fumarate (taken twice a day).
Fingolimod, another oral medication taken once a day, can be prescribed if a patient is having relapses despite taking a beta interferon medication for at least a year.
Natalizumab, which is given as an intravenous infusion every four weeks, is highly effective and may reduce the number of relapses by up to 7%. The drug is prescribed in cases of very active relapsing remitting MS (defined as two or more relapses in one year or if serial MRI scans showed increasing number of MS lesions). However, with increasing efficacy comes the risk of significant side effects such as the development of a viral infection called Progressive Multifocal Leuco-encephalopathy (PML) which can be very serious. There are now methods and monitoring protocols in place to assess the risk of developing this complication.
Finally, alemtuzumab has been available since 2014 and can be prescribed for active and highly active relapsing remitting MS. It is given as an intravenous infusion in two treatments (the first for five days, the second for three days) separated by 12 months. The most serious side effects include thyroid gland disorders, ITP which affects blood clotting and kidney problems.
Patients with MS have been shown to have lower 25,OH vitamin D levels than healthy controls. Adequate levels of vitamin D have been associated with a reduced risk of developing MS as well as reducing the risk of relapses. However, controversy still remains regarding this issue. A recent review from Canada concluded that "the role of high dose vitamin D supplementation in MS treatment and prevention remains unclear". It is reasonable that, at the very least, patients who are vitamin D deficient should be prescribed supplementation to normalise vitamin levels.
There are numerous trials addressing all aspects of MS - these include:
- The MS-SMART study is looking at the role of three drugs in secondary progressive MS – amiloride, fluoxetine and riluzole.
- The MS-STAT study is investigating the role of simvastatin (usually prescribed for high cholesterol) also in secondary progressive MS.
- The anti-epileptic drug pheytoin has been investigated as a neuro-protective agent in optic neuritis.