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Multiple Sclerosis

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Overview

Multiple sclerosis (MS) is a chronic and inflammatory demyelinating disease of the central nervous system. Multiple episodes of inflammation lead to the formation of scar tissue (sclerosis) along neurones leading to slowed signal transmission. By definition, the damage in MS must be disseminated in time and space (i.e. damage has occurred at different sites and at different times).

The cause of MS is not fully understood; however, it appears to be linked to genetic and environmental factors (e.g. viral infections in early life).

Epidemiology

  • Twice as common in women than in men
  • Prevalence is highest in >60 years of age
  • Women are affected at an earlier age 

Disease Patterns

Relapsing-remitting multiple sclerosis

  • The most common type
  • Characterised by acute attacks followed by periods of remission

Secondary progressive multiple sclerosis

  • Can follow on from relapsing-remitting multiple sclerosis
  • Characterised by gradually more or worse attacks with fewer remissions
  • Around ½ of patients with relapsing-remitting MS develop secondary progressive MS during the first 10 years of illness

Primary progressive multiple sclerosis

  • Characterised by worsening symptoms from the beginning without periods of remission

Clinically isolated syndrome (CIS)

  • Where patients experience signs and symptoms that may represent the onset of MS
  • There has only been one attack, so patients have not met the “disseminated in time and space” criteria for MS
  • They may go on to develop MS

Risk Factors

  • Female sex
  • Family history
  • Inadequate sunlight exposure
  • Vitamin D deficiency
  • Smoking
  • Autoimmune disease

Presentation

There is a wide range of symptoms that patients with MS can present with, most patients have fatigue and lethargy. Some other features are:

  • Optic neuritis – the most common presenting feature
  • Internuclear ophthalmoplegia – inability to move eyes together when looking to the side
  • Diplopia
  • Uhthoff’s phenomenon – worse vision after an increase in body temperature
  • Pins and needles
  • Numbness
  • Neuropathic pain e.g. trigeminal neuralgia
  • Leg cramping
  • Ataxia
  • Spasticity – commonly in the legs and can be painful
  • Urinary/faecal retention
  • Effects on intelligence – loss of memory > language skills

Differential Diagnoses

B12 deficiency

  • Patient may have a strict diet e.g. vegan or disorders of terminal ileum e.g. surgery/disease
  • Macrocytic anaemia may be present
  • Vibration and proprioception impaired

Guillain-Barre syndrome (GBS)

  • Progressive symmetrical weakness of the limbs that are classically ascending
  • There may be a history of infection e.g. gastroenteritis 
  • Symptoms are mainly motor with mild sensory symptoms
  • Lumbar puncture shows increased protein and normal white cell count – albuminocytologic dissociation
  • Upper motor neurone signs (UMN) signs are not typically seen as it is a peripheral neuropathy 

Amyotrophic lateral sclerosis (ALS)

  • Symptoms are upper motor neurone lesions or lower motor neurone lesions
  • Sensory symptoms/signs are absent
  • The vision, extraocular muscles, and cerebellum are unaffected
  • Dysphagia may be present, but there are fasciculations present unlike in MS

Investigations

Overview

  • MRI brain and spinal cord with contrast – test of choice:
    • There needs to be evidence of lesions disseminated in time and space to diagnose MS – shows hyperintensity in the periventricular white matter
  • Lumbar puncture:
    • Oligoclonal bands present
    • Elevated IgG and synthesis of IgG
  • Blood tests to rule out other causes:
    • FBC
    • Glucose
    • U&Es
    • LFTs
    • TFTs
    • B12 and folate

Diagnosis

McDonald Criteria

In summary, to diagnose MS there must be evidence of lesions disseminated in space and time. The disease pattern should be established based on the history and re-evaluated as time goes on and more information is available

Management

Acute relapse

  • 1st-line: oral or IV methylprednisolone

Ongoing management

Treatment involves the use of disease-modifying drugs based on patient characteristics. These may be:

  • Glatiramer acetate
  • Natalizumab
  • Fingolimod

Symptom management

  • Fatigue:
    • 1st-line: exclude other causes then trial amantadine + CBT
  • Spasticity:
    • 1st-line: baclofen or gabapentin
    • 2nd-line: tizanidine or dantrolene
    • 3rd-line: diazepam
    • Specialists may initiate THC:CBD spray
  • Oscillopsia (vision appears to oscillate despite actually being stationary):
    • 1st-line: gabapentin
  • Emotional lability – involuntary laughing/crying due to frontal lobe lesion
    • 1st-line: amitriptyline
  • Neuropathic pain:
  • Bladder symptoms:
    • 1st-line – investigate for UTI + assess postmicturition residual bladder volume via ultrasound scan:
    • Urge incontinence:
      • Consider toilet arrangements/intermittent self-catheterisation
      • Consider anticholinergics e.g. oxybutynin/tolterodine 

Monitoring and Patient Advice

Monitoring

Patients should have a comprehensive review at least once a year and should be followed by healthcare professionals with expertise in MS. The reviews are tailored to the needs of the person assessing mobility, signs and symptoms, the disease course, general health, social activity and participation, carers, and caring.

Patients with severely reduced mobility should be assessed for complications such as pressure ulcers/contractures (shortening of tendons/muscles/ligaments that limits joint movement)

If relevant, refer people with MS to palliative care services and end-of-life care when appropriate.

Patient Advice

Patients should be encouraged to maintain a healthy lifestyle through exercise and a balanced diet, stop smoking, and reduce alcohol intake, and should be offered help with these changes

Patients should be educated on the nature of MS and how its disease pattern and should be safety-netted on the signs and symptoms of acute flares and to seek help should these arise

Complications

  • Impaired mobility
  • Cognitive impairments
  • Urinary/bowel dysfunction
  • Sexual dysfunction
  • Visual impairment
  • Depression
  • Fatigue
  • Osteoporosis
  • Urinary tract infections

Prognosis

  • Around 1/4 of patients have a non-disabling form of MS
  • 1/5 of cases are primary progressive and have a poorer prognosis
  • Around 15% are severely disabled within a short year
  • 5% have frequently occurring relapses without recovery causing disability and early death
  • Relapse rates are reduced during pregnancy but increase again after delivery

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