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Neurology clinic - multiple sclerosis

Consultant neurologist Dr David Barnes discusses this case of a young woman presenting with symptoms suggestive of an inflammatory spinal cord lesion.

A 23-year old woman comes to see you with a history that, three days previously, she had woken with tingling in both feet. By the following morning, the symptoms had spread to the whole of both legs, and yesterday, to her lower ribs. She also mentioned a tight feeling around her abdomen, more marked after her morning shower. She is otherwise in excellent health and has no past history of any neurological problems.

On full neurological examination, she was unable to feel vibration on the big toes of both feet, but otherwise, there was nothing to find.

You refer her to neurology suspecting a spinal lesion and she undergoes an MRI of her brain and cord later that week. The cord images demonstrate an inflammatory lesion, and the brain shows associated lesions typical of MS, confirming dissemination of the disease in space. At this stage, however, she is diagnosed as having a clinically isolated syndrome (CIS) because, although the brain changes suggest she has a high risk of developing MS, a definite diagnosis cannot be made without demonstrating dissemination of the disease process in time as well as in space.   

The neurologist therefore decides to repeat the brain MRI scan after three months, and this scan demonstrates several new lesions including a periventricular gadolinium-enhancing lesion.  This evidence of new activity allows the neurologist to confirm that the disease is now disseminated in time as well as in space, and thus a definite diagnosis of MS using the McDonald criteria (2001) can be made.  The purpose of the McDonald criteria is to allow a diagnosis of MS to be made by MRI criteria, whereas previously, it was always necessary to await a second clinical attack in a new anatomical site according to the Poser criteria of 1983.  Underlying the introduction of these new criteria was the emergence of disease-modifying therapies such as the interferons, and evidence that early treatment may benefit patients in the longer term.  Therefore, by using MRI criteria, without the need to await a second clinical attack, treatment can be started earlier in the course of this disease.

Following diagnosis, your patient is started on teriflunomide, a new first-line oral disease-modifying therapy (DMT).

Features

This patient presents with a history virtually diagnostic of sensory cervical myelitis, a very common CIS to be the presenting feature of relapsing-remitting MS. The purely sensory features, tempo of onset over days, associated tight feeling sometimes referred to as the ‘MS hug’, and exacerbation by heat (Uhthoff’s phenomenon), as well as her age and sex make the diagnosis almost certain. However, as the patient’s symptoms were worsening, alternative cord pathology cannot be excluded clinically, so an urgent neurological referral is indicated. Has she already noted improvement in her symptoms, there would be less urgency.

Diagnosis

The diagnosis of MS has always been, and remains today, dependent upon demonstrating dissemination of disease activity in both time and space. However, as discussed above, in a patient with CIS, the McDonald criteria now allow a definite diagnosis to be made on the basis of MRI findings alone, whereas in the past this diagnosis involved having to wait for a second clinical attack in a different anatomical site, for example optic neuritis.1  In day-to-day practice, it is nevertheless still the case, that the diagnosis is usually made on the basis of clinical disease activity with supporting MRI evidence.

From the general practice perspective, clinical suspicion of the onset of MS should always be aroused by a history of subacute onset of uncomplicated neurological symptoms particularly in young women.  It is rare at onset of the disease for the patient to be polysymptomatic, and characteristically the symptoms develop over days, stabilise for a few weeks, then resolve gradually.  Symptoms are not intermittent and do not last hours or months.

Typical syndromes are dictated by the sites in the CNS most commonly affected by MS.  Thus the optic nerves (optic neuritis) and cervical cord (sensory cervical myelitis) are very common, but cerebellar and brainstem attacks (with dysarthria, diplopia and vertigo) are also seen in many patients early in the disease course.  Conversely, stroke-like syndromes such are hemiplegia, dysphasia, homonymous hemianopia and pure hemisensory symptoms are rare in MS and should raise a “red flag”, as should severe spinal cord lesions with paraplegia (transverse myelitis). 

Broadly speaking, if a patient with CIS has a brain MRI, the long-term risk of progression to MS is about 80% if the scan is suggestive of demyelination, but <20% if it is normal.2

Managing a patient with CIS remains a dilemma for neurologists. Simply having a brain MRI, regardless of the result, is likely to have important implications for the patient in terms of, for example, life insurance. I do discuss these issues with CIS patients before arranging brain imaging, because almost all of them are aware of the relationship between their CIS and possible MS, or at least fear that they may have the disease. In my experience, most patients will opt to have the brain scan because they want to know, for whatever personal reasons.

Management

Each year that passes brings stronger evidence that treating evolving MS earlier rather than later does improve long-term disability. We’ve learned that in America and many European countries, it is now routine practice to start DMT in patients with CIS and brain scan typical of MS without waiting for a definitive diagnosis. While the current UK criteria for starting the various DMT restrict our options, our mindset is certainly moving strongly in the direction of treating early with DMT and this will become standard practice in the foreseeable future.

There are currently six licensed first-line DMT available for MS (two of them oral), and three second-line treatments. There will undoubtedly be more in the future, and they will be more effective. Therefore, an early diagnosis of MS is now not only important in principle, but also, in practice.

Dr David Barnes is a consultant neurologist at St Peter’s Hospital, Chertsey and St George’s Hospital, London

References

  1. McDonald WI, Compston A, Edan G et al. Recommended diagnostic criteria for multiple sclerosis. Ann Neurol, 2001;50(1):121-27
  2. Miller DH, Chard DT, Ciccarelli O. Clinically isolated syndromes. Lancet Neurol, 2012;11(2):157-69


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Readers' comments (3)

  • Interesting article thank you

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  • very clearcut and useful for GP.

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  • I'm wondering why my patient has had to wait a year to get treated. I'm rather cross about it. (Anonymous for potential patient identification reasons)

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