MS is an autoimmune, inflammatory condition of the central nervous system.  Usually, the information occurs in discrete areas, and at distinct times, leading to what we would recognise as a “relapse”.  The inflammation typically affects the white matter of the central nervous system, causing demyelination and axonal damage.  Usually, after a period of neurological symptoms, or disability, patients make a gradual recovery.  This is usually referred to as “remission”.

How common is it?

Incidence and prevalence figures are incredibly difficulty memorise, and are generally about as much use as a chocolate teapot when it comes to clinical practice.  That said, for reasons that are never entirely clear to me, people setting medical school exams seem to think this sort of information is vital.

With respect to MS, the incidence is 7/100,000, and the prevalence is about 120/100,000.  Given the UK population is currently around 64 million, this means that there are about 4500 new cases of MS diagnosed each year, and around 80,000 people living with MS on a daily basis.

As is often the case with autoimmune conditions, MS is more common in women, and typically presents when patients are in their 20s and 30s.  Onset after the age of 50 is rare, but not unheard of.  It is far more common in white populations, particularly in the northern hemisphere.

How does it present?

Symptoms depend entirely on the site of central nervous system inflammation.  Inflammation in the visual pathways leads to visual symptoms; inflammation in the motor tracts leads to motor problems; inflammation in the sensory regions leads to sensory symptoms etc. It’s that simple!

Usually, the inflammatory process builds up over a number of days, or weeks.  For this reason, patients rarely present with acute problems, worst at the moment of presentation.  The gradual evolution can be quite helpful when trying to categorise a presentation as “inflammatory”.

The first clinical presentation in MS is usually called an “episode “.  Currently, we tend to refer to the initial presentation as a “clinically isolated syndrome” (CIS).  Predicting which CIS patients will go on to develop MS is a bit of a dark art.  If, at the time of presentation, there are signs of other episodes of inflammation having occurred, usually by examining the MRI scans, then there is a roughly 50% chance of developing clinical “MS”by 2 years.  This rises to around 80% by 20 years.  If, however, at presentation the MRI scan is reassuringly normal, then the risk is much lower (20% by 20 years).

Further discrete neurological symptoms, suggestive of new patches of inflammation, are usually referred to as a “relapse”.  It is at this point that a patient fulfils the clinical definition of “multiple sclerosis”, as they have now had more than one clinically distinct inflammatory presentation.

How does it behave?

Usually, relapses gradually recover, although they can take several weeks, or months, to do so.  This recovery phase is referred to in the literature as “remission”.  Hence, the most common clinical phenotype is known as “relapsing-remitting” MS.

Over time, patients can develop progressive neurological disability.  This is usually referred to as “secondary progression”.  Relapses may continue to happen during this phase although it is not uncommon for clinical relapses to become less prominent over time.

Approximately 20% of patients will present with a primarily progressive form of the condition, in the absence of obvious relapses.  There is a very gradual decline in neurological function, rather than the dramatic changes from baseline seen during a relapse.

I try not to get too hung up on the “type” of MS my patients have. I focus more on what symptoms they have. As there are effectively still no useful treatments for progressive decline in function, relapses become an important feature as they define the eligibility for the licensed therapies – if that makes sense. Put simply, if you are not relapsing, then there are very few treatment options (if any).

Here is a nice graph of the “types” of MS. I’ve “borrowed” it from someone else so no plaudits to me please.




What are the main problems faced by patients?

The are a number of “typical” presentations that patients experience.  The following section is by no means exhaustive, but should give you some idea of what to look out for when faced with a new presentation.

Optic neuritis

Obviously, patients are rarely going to walk up to you and tell you that they have “optic neuritis”.  In this scenario, patients will typically describe pain at the back of the eye, particularly when moving it, coupled with a reduction in visual acuity.  Usually, there is a distortion of central vision which, when severe, leads to significant problems with reading and colour vision.  The visual disturbance starts off quite subtly, at least to begin with, and gradually becomes more severe as the days pass.

On examination, look out for a dilated pupil.  This may not respond terribly well to direct stimulation with a bright light, but may constrict more briskly when the normal eye is stimulated.  This leads to a relative afferent pupil defect (RAPD). 

Fundoscopy may reveal a swollen optic nerve head (papillitis), although in many cases the optic nerve looks normal.  After recovery from optic neuritis, the optic nerve head can look rather pale.  We refer to this as “optic atrophy”.

Transverse myelitis

This presentation sounds complicated but actually just “does what it says on the tin”.  There is transverse inflammation (-itis) of the spinal cord (myel-).  Sometimes, the whole cord is involved and, on other occasions, only half.  In this latter presentation, we meet another eponymous syndrome delivered of exam question setters.  A hemi-cord lesion will lead to ipsilateral weakness, ipsilateral disturbance of vibration and joint position sense and contralateral disturbance of temperature and pain sensation.  This is the essence of a Brown-Sequard syndrome.


brown sequard


Much more common is a subtle disturbance of sensory function, which typically begins in one leg and often creeps up, over the space of a  few days or weeks.  Often, although both legs are affected, one is more so than the other.  It is not at all unusual for patients to develop bladder symptoms at around the same time. 

Patients may also experience a tight band like sensation around the abdomen -think of this as a sort of dermatomal loop, constricting the skin.  One of my female patients recently described the sensation as “like I was wearing a tight bra strap, but without the bra strap”.

A word of warning - the inflammatory lesion is often much higher than you would expect from the sensory symptoms.  It usually worth looking in the cervical spine, even if the century symptoms seem to finish at the top of the legs.
Non-specific symptoms
  • Lhermitte’s symptom – an electric shock or tingle that passes down the spinal column when the neck is flexed.
  • Uhthoff phenomenon – a worsening of symptoms in hot weather or after a warm bath or shower.
  • Fatigue – this word rarely does justice to the sense of overwhelming exhaustion that many patients with MS experience.  For some of my patients fatigue is, without doubt, the most debilitating and troublesome symptom. 
  • Spasms – these are usually seen in patients with significant motor tract lesions, who have then gone on to develop significant spasticity.  Spasms can be prolonged and painful and require careful management.
  • Bladder problems – urinary frequency and urgency are extremely common.  They cause untold misery for many patients and need specialist input to optimise symptom control.  Intermittent self-catheterisation is often undertaken by patients, if they have a significant bladder residual after attempting to avoid.
  • Cognitive symptoms – these are very common in patients, particularly if they are using medication to control other symptoms.  Frank dementia syndromes are still considered to be relatively rare, although I suspect that they will be increasingly recognised over the next 10-20 years.
  • Pain – this is again a huge issue for some patients.  It can be difficult to manage, and we tend to focus on neuropathic pain medications such as anti-epileptic or anti-depressant type medications.
  • Mood – understandably, a diagnosis of MS in young adulthood has a huge impact on mood.  Anxiety and depression are not uncommon.

How do we diagnose it?

The mainstay of diagnosis is MR brain and spine imaging.  As the resolution of MR scanners has improved, the need for ancillary investigations has diminished.  In most cases, a good clinical history, coupled with a detailed neurological examination and a decent MRI scan will liar diagnosis to be made with confidence.

We are principally interested in the T2 and flair sequences, as these tend to be more sensitive for inflammatory demyelination.  Lesions can crop up just about anywhere in the white matter but peri-ventricular and juxta-cortical areas are particularly vulnerable.  The cerebellum and brainstem or also common sites of inflammation as, obviously, is the spinal-cord.

ms sagittalms mri

Sometimes, it can be helpful to ask for a contrast-enhanced scan.  New lesions will enhance with contrast whereas older lesions will not.  A single MRI scan with enhancing and non-enhancing lesions therefore allows you to demonstrate “dissemination in time” and “dissemination in space”.

ms mri with gad
note the enhancement of one lesion (short arrow), but not the others (long arrow), which must therefore be older

Obviously, the clinical history is usually what gives you the “dissemination story”.

If the diagnosis is in doubt then a lumbar puncture may sometimes be performed.  Usually, the constituents of the CSF are all normal, with the exception of oligoclonal bands.  These are really antibodies floating around in the CSF. If there is inflammation restricted to the central nervous system then the OCBs will be present only in the CSF, and not in a blood sample, taken at roughly the same time.  Hence, you are looking for unmatched OCBs – present in the CSF and not in the serum. OCBs present in both are of limited diagnostic help.

Very occasionally, one can test the amplitude and speed of conduction in the optic pathway, using a test called a visual evoked potential.  Delay on one side, when compared to the other, can suggest a prior episode of optic neuritis.  In practice, this test is rarely performed these days.

Diagnostic criteria exist, which have recently been revised.  Details of these are provided below. They are mostly used for research studies and still confuse me so its okay just to know they exist!


What is the differential diagnosis?

A number of conditions can catch you out.  Obviously, a proportion of patients with inflammatory demyelination will only ever have one episode.  As such, they are not “multiple” anythings.  It is perfectly possible to have an episode of transverse myelitis, or indeed optic neuritis, without going on to develop MS.

Some patients can present with a fulminant inflammatory disorder called Acute Disseminated Encephalomyelitis (ADEM).  This typically presents following infection or vaccination and patients are usually extremely unwell. Once seen, never forgotten (but, to be fair, rarely seen in adults).

Demyelinating variants also exist.  The best characterised of these is Neuromyelitis Optica (NMO).  I would not expect medical students to need to know much about NMO.  Basically, the classic presentation is with bilateral optic neuritis and longitudinal extensive myelitis.  As you might imagine, patients present with profound visual loss and either paraparesis or tetraparesis.  Specific antibodies, aquaporin-4, are now known to associate with this condition.  Follow the links to the references below for more information. Also, bear in mind that the spectrum of NMO presentations is broad and it can present a bit more like MS.

More recently, anti-MOG antibody disease (MOGAD) has also been described. MOG stands for Myelin Oligodendrcyte Glycoprotein and antibodies against this myelin sheath protein can lead to a number of demyelinating presentations. Again, longitudinal extensive myelitis is part of the syndrome but patients can also present with active CSF, encephalopathy and in a number of more typical “MS-like” fashions too.

Systemic autoimmune conditions, such as SLE, sarcoidosis and vasculitis can all present with similar symptoms.  It is worth considering these, at least in passing, although there are all fairly rare in the context of presentation is typical of MS.  Most can be ruled out with a series of blood tests looking at inflammatory markers and autoimmune screens.

A word of warning about MRI scans reported by non-specialist radiologists.  MRI scans quite often pick up small areas of high signal in the white matter.  In a well patient these are rarely significant and may be slightly more common in patients with migraine.  In older patients, particularly those with vascular risk factors, then small vessel vascular disease is a far more common explanation.  Unfortunately, many radiologists feel the need to report that they "cannot rule out demyelination".  This then leads to mass panic, when the report is received and, some months later, and needlessly concerned patient is eventually seen by a neurologist who has to then un-diagnose something which should never been diagnosed in the first place.

What can we do about it?

There are some excellent reviews about treatment options below.  These go into a huge amount of detail, which may not be necessary for medical exams.

Basically, the first thing to say is that some patients do not require much in the way of treatment.  Treatment decisions are, of course, highly individual.  Some patients would prefer to “watch and wait”, rather than embarking on a specific course of treatment.

Personally, I feel it is extremely important that patients are supported after a diagnosis, both by seeing a specialist in the area and being linked with a multidisciplinary team, led by an MS specialist nurse.  It is vital that patients are well-informed about both the condition, the symptoms and the treatment options, so that they can make an informed decision and feel able to do so.

Preventative treatment options have evolved considerably over the last few years, and continue to do so.  I tend to explain the options as “rungs on a ladder”.  With each step on the ladder, treatments become more effective in terms of reducing relapses, and preventing new lesions appearing on MRI scans.  The trade-off for this increased efficacy is an increase in risk.

Some specialists are now advocating an “induction” approach where you go in hard with a highly effective treatment, get the inflammatory response under control and then, potentially, step down again. We’re not sure what option – induction or escalation – is better and there are studies running at the moment to understand this better.

A discussion for another day is how to balance your own risk/benefit personality traits against those of the individual sitting opposite you in a clinic room.  A very risk averse clinician will probably end up talking patient out of vital treatments that they might otherwise have gone for.  Of course, it also works the other way round and managing this dynamic is part of the “art” of medicine.

The first rung on the treatment ladder are the self-administered injectable therapies, such as interferon.  I usually tell patients that these reduce relapses by, on average, about 30%.  They have a variety of side effects, not least the inconvenience and discomfort of having to inject yourself on a regular basis.  That said, the risks associated with treatment are pretty low. There is also an oral medication now as well.

Rung two on the ladder includes a number of oral medications – dimethyl fumarate, fingolimod and siponimod.  Basically, these medications reduce relapses by close to 50%.  The risk of opportunistic infections is considerably higher, reflecting the greater impact the drugs have on immune surveillance.  There have been fatalities using these medications and, rarely, a serious complication called progressive multifocal leucoencephalopathy (PML).  If patients are going to embark on this sort of treatment then they need to be consented appropriately and monitored closely. 

Lastly, there are expensive, more risky intravenous infusion therapies – Natalizumb, Alemtuzumab, Ocrelizumab, Rituximab etc.  These medications need to be administered either as a day case or inpatient.  They reduce relapses by close to 70% but have a considerably higher complication rate, including much higher rates of PML.  Whilst not a standard first choice therapy, for patients with highly active inflammatory disease and multiple relapses they can be literally life-saving and life-changing.

For some patients, stem cell transplant can offer hope and there is a lot of interest in this at the moment. It’s definitely a high risk option and not many people have had it done, but it does have potential and we are likely to learn a lot about MS in the process.

MS escalation ladder


Managing an MS relapse

The first thing to say is that many patients with an intercurrent infection will notice a worsening of their MS symptoms.  This is sometimes misdiagnosed as a “relapse”.  It is therefore important, before diagnosing a relapse, to make sure that you are not dealing with a resurgence of previous symptoms, triggered by infection.  In practice, this usually means taking some basic blood test, including inflammatory markers, and making sure that the patient does not have a urinary tract infection.

Assuming that a relapse has been confidently diagnosed then one can consider the use of high-dose methyl prednisolone to help reduce the duration of the relapse symptoms.  Is important to tell the patient that the treatment will not get them better than they are natural recovery would have done – they may just get the bit quicker with treatment.

Many units have now switched to using five days of oral methyl prednisolone (500 mg daily for five days) as this has been shown to be as effective as intravenous high-dose methyl prednisolone (1000 mg iv for three days).


Some useful references and files, should you want a good review of the topic.

1. Coles, A. (2009). Multiple sclerosis: THE BARE ESSENTIALS. Practical Neurology, 9(2), 118–126.

Coles_2009_prac_neurol_MS bare essentials

2. Rice, C. M. (2014). Disease modification in multiple sclerosis: an update. Practical Neurology, 14(1), 6–13.

rice_2014_prac_neurol_DMT in MS

3. Scolding, N., Barnes, D., Cader, S., Chataway, J., Chaudhuri, A., Coles, A., et al. (2015). Association of British Neurologists: revised (2015) guidelines for prescribing disease-modifying treatments in multiple sclerosis. Practical Neurology, 15(4), 273–279.

ABN guidelines for MS treatment_2015

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