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Multiple Sclerosis

From Mediwikis

This autoimmune disease is characterised by inflammation of the myelin sheaths around the axons of nerves, especially in the paraventricular areas, brainstem, basal ganglia, spinal cord, and optic nerve. The inflammation then causes demyelination, impeding the conduction of the action potential.

Symptoms of Multiple Sclerosis.png

Signs & Symptoms

Any nerve can become demyelinated, so someone with MS can present with any neurological sign. Hallmark features are:

  • Sensory Disturbances
  • Visual disturbance/loss
  • Weakness
  • Double Vision
  • Detrusor Sphincter Dyssynergia - this is where the bladder contracts but the pelvic floor fails to relax, preventing micturition leading to high pressures within the bladder and back pressure on the kidneys. In the long term this increased pressure can lead to kidney damage and renal failure. (Management = intermittent catheterisation to decompress the bladder)

Other interesting signs:

  • Internuclear Ophthalmoplegia- On looking to one side, the abducting eye moves normally, the adducting eye fails to move/ is delayed. The abducting eye then shakes. This is caused by a lesion in the Medial Longitudinal Fasciculus, easily remembered as the MILF.
  • Lhermitte's sign- Bending the head forward causes an "electric shock" pain, lesion is in cervical cord.
  • Uhthoff's phenomenon- Worsening of MS symptoms in heat- remyelination is not as organised, so the fatty myelin melts.

Aetiology

  • Female:Male 2:1
  • Some weak genetic predisposition
  • Linked to geographical birthplace- distance from equator

Diagnosis

Multiple Sclerosis is still a clinical diagnosis- there's no golden standard investigation. The key to diagnosing multiple sclerosis is in the name- it has to show multiple episodes of CNS disturbance, separated by time and space, with no better explanation.

McDonald Criteria

As found in McDonald et. al

Clinical Presentation Additional Data Needed
* 2 or more attacks (relapses)
* 2 or more objective clinical lesions
None; clinical evidence will suffice (additional evidence desirable but must be consistent with MS)
* 2 or more attacks
* 1 objective clinical lesion
Dissemination in space, demonstrated by:
* MRI
* or a positive CSF and 2 or more MRI lesions consistent with MS
* or further clinical attack involving different site.
Dissemination in Space (DIS) can be demonstrated by the presence of 1 or more T2 lesions in at least 2 of 4 of the following areas of the CNS: Periventricular, Juxtacortical, Infratentorial, or Spinal Cord.
* 1 attack
* 2 or more objective clinical lesions
Dissemination in time (DIT), demonstrated by:
* MRI
* or second clinical attack
No longer a need to have separate MRIs run; Dissemination in time, demonstrated by: Simultaneous presence of asymptomatic gadolinium-enhancing

and nonenhancing lesions at any time; or A new T2 and/or gadolinium-enhancing lesion(s) on follow-up MRI, irrespective of its timing with reference to a baseline scan; or Await a second clinical attack. [This allows for quicker diagnosis without sacrificing specificity, while improving sensitivity.]

* 1 attack
* 1 objective clinical lesion
(clinically isolated syndrome)
' Dissemination in space and time, demonstrated by:

For DIS: 1 or more T2 lesion in at least 2 of 4 MS-typical regions of the CNS (periventricular, juxtacortical, infratentorial, or spinal cord); or Await a second clinical attack implicating a different CNS site; and For DIT: Simultaneous presence of asymptomatic gadolinium-enhancing and nonenhancing lesions at any time; or A new T2 and/or gadolinium-enhancing lesion(s) on follow-up MRI, irrespective of its timing with reference to a baseline scan; or Await a second clinical attack.

Insidious neurological progression
suggestive of MS
(primary progressive MS)
One year of disease progression (retrospectively or prospectively determined) and

two or three of the following:
1. Evidence for DIS in the brain based on 1 or more T2 lesions in the MS-characteristic (periventricular, juxtacortical, or infratentorial) regions
2. Evidence for DIS in the spinal cord based on 2 or more T2 lesions in the cord
3. Positive CSF (isoelectric focusing evidence of oligoclonal bands and/or elevated IgG index)

Investigations

These are used to exclude other pathologies:

  • MRI
  • Lumbar Puncture- Oligoclonal bands of IgG distinct from the blood indicate CNS inflammation.
  • Evoked Potentials- in the case of visual loss

Disease Course

Progression of types of MS

Attack Onset

  • Relapsing Remitting
  • Secondary Progressive

Progression Onset

  • Primary Progressive
  • Progressive Relapsing

Treatment

Note, these are for attack onset MS, the secondary progressive is more difficult, and primary progressive often doesn't respond to therapies.

Relapses

It is possible to just leave a relapse to run its course, rather than trial medication (and the associated side effects). Steroids such as methylprednisalone are useful for fresh inflammation, however.

Disease Modifying Therapies

  • Interferon β, copaxome. Injected at home by patient. Reduces relapse rate by ~1/3
  • Natalizumab- Monoclonal Antibody. Anti-VLA-4 "teflon coats" the white blood cells, so they cannot adhere to the blood vessels and sneak through to cause inflammation. 81% reduction in relapse rate, 2/3 reduction in disability. Be wary of reactivation of JC virus in these immunosuppressed patients.

References