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How not to miss multiple sclerosis

Worst outcomes if missed

Disability and increased mortality – there is now published data suggesting that starting anti-inflammatory disease modifying therapies early reduces long term disability and mortality in MS.1 Therefore early diagnosis allows early treatment, producing better outcomes.


The UK is an area of high prevalence of MS, approximately one in every 1000 of the population. The average age of onset is 30 years and the female to male ratio is 2 to 1, though the incidence appears to be increasing in the female population. This and the higher  prevalence with increasing  latitude has been cited as evidence that vitamin D and sun exposure play an important role in the causation of MS.2

It must be remembered that 80% of MS patients start with a relapsing-remitting course (RRMS), developing secondary progressive disease (SPMS) after 10 to 15 years. Whilst 20% present with a progressive deterioration from onset - primary progressive MS (PPMS) – this population is older and a greater proportion are male. Before disease modifying treatments, 50% of patients would require a walking aid after 15 years of the condition, with high rates of unemployment and divorce.

Symptoms and signs

Sensory, ophthalmic, motor and cerebellar symptoms are the most common presentations.  Optic neuritis, myelitis, inter-nuclear ophthalmoplegia are characteristic presentations. Sensory symptoms are probably the most challenging as sensory disturbance is a common complaint. However, a sensory level indicating spinal cord involvement is very suggestive of demyelination, in particular partial cord signs such as Brown-Séquard syndrome.

Other features with strong relationship to MS are L’Hermittes phenomenon, where the patient experiences an electrical sensation in the limbs on neck flexion, and Uhthoff’s which is a worsening of symptoms associated with an increase in body temperature e.g. exercising or hot shower.

Five key questions

  • Speed of onset, duration of symptoms – should develop over days, last more than a day
  • Other concurrent neurological symptoms – many patients with CIS are polysymptomatic
  • History of sensory, ophthalmic, motor, cerebellar symptoms – often history of undiagnosed events
  • Fluctuation with body temperature – Uhthoff’s phenomenon
  • Family history – having affected family member increases risk of MS

Differential diagnoses

The first presentation of MS is described as a ‘clinically isolated syndrome’ (CIS). Whilst the clinical presentation can mimic other pathology of the CNS, such as stroke, tumours and infection, the subacute onset of symptoms in a systemically well young person points to a demyelinating process.

Often the challenge is deconstructing the diagnosis of MS, made by an enthusiastic A& E junior or by the patient from the internet. Unfortunately sensory symptoms are common in the population – from carpal tunnel, meralgia paraesthetica, to restless legs – all of which may lead to a misdiagnosis of MS.


As in all medical conditions, history and examination are key to suspecting the diagnosis, and MS can be diagnosed clinically.

MRI is the main test for confirming the diagnosis. The most recent diagnostic criteria now allow the diagnosis of MS to be made at presentation with a CIS.3 The presence of multiple MRI lesions and an asymptomatic active lesion confirm dissemination in space and time,  supporting the diagnosis of MS. Previously, a second clinical episode would be required before MS was considered, delaying the diagnosis and treatment.

 Five red herrings

  • Resolving symptoms – relapsing remitting MS will resolve, often completely, keep MS in mind
  • MRI lesions – not all lesions on MRI are demyelinating, many are vascular, do not diagnose MS on MRI alone
  • Normal brain MRI – can present with spinal cord lesions alone
  • In MS patients – fatigue and other symptoms can be due to other pathologies, thyroid, anaemia
  • Patient not born in UK – appears to be increasing in frequency in overseas populations

Dr Ben Turner is a consultant neurologist with subspecialty interest in MS at Barts and the London NHS Trust.

Dr Turner is actively involved in, and chief UK investigator for, phase II and III clinical trials in MS at Barts Health and UCLP. For details of the trials please email

Competing interests:  Dr Turner has received travel grants and honorarium from Biogen, Novartis, Serono, Sanofi-Aventis, Genzyme, TEVA.


  1. Goodin DS, Reder AT, Ebers GC et al. (2012) Survival in MS: a randomised cohort study 21 years after the start of the pivotal IFNbeta-1b trial. Neurology, 78 (17); 1315-1322
  2. Ramagopalan SV, Maugeri NJ, Handunnetthi L et al. (2009) Expression of the multiple sclerosis-associated MHC Class II Allele HLA-DRB1*1501 is regulated by vitamin D. PLoS Genetics, 5 (2); e1000369
  3. Polman CH, Reingold SC, Banwell B et al. (2011) Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Annals of neurology, 69 (2); 292-302

Further reading

Tattersal R, Turner B. (2000) Brown-Séquardand his syndrome. The Lancet, 356 (9223); 61-63