multiple%20sclerosis
MULTIPLE SCLEROSIS
Multiple sclerosis is an acquired chronic immune-mediated inflammatory disease of the brain and the spinal cord characterized by presence of multiple discrete areas of myelin loss within the CNS and subsequent axonal degeneration.
Affects more women than man; however, men are more likely to have a malignant clinical course.
A multiple sclerosis attack is usually characterized by any neurological disturbance with minimum 24 hours duration, in the absence of fever or infection.

Pharmacotherapy

Disease-Modifying Treatment

  • Goals: To reduce the rate of disease/disability progression, decrease the number of relapses, and help reduce development of new lesions
  • None of the agents provide sustained remission, halt progression or alleviate long-term disability
  • Risks vs benefits need to be reviewed with patient before starting therapy
  • Some live vaccines may be contraindicated in patients with multiple sclerosis that is being treated with disease-modifying therapies

Immunomodulators

  • Eg Interferon beta-1a, Interferon beta-1b, Glatiramer acetate
  • Glatiramer acetate
    • Alternative to Interferon in patients with active relapsing-remitting multiple sclerosis
    • Has been shown to reduce the clinical relapse rate (either clinically or by magnetic resonance imaging) in patients with relapsing-remitting multiple sclerosis
    • Relapsing-remitting multiple sclerosis patients may also have a slowing of sustained disability progress
    • One study showed beneficial effects by magnetic resonance imaging; however, this is only seen after 6 months of treatment
  • Interferon beta-1a (intramuscular and subcutaneous) and 1b (subcutaneous)
    • Used to reduce frequency and severity of acute relapses in relapsing forms of multiple sclerosis
    • May consider use in any patient at risk for developing clinically definite multiple sclerosis (CDMS)
    • There may be certain populations of patients who are better candidates for therapy than others but it is yet to be determined how to distinguish these patients
    • Has been shown to reduce the attack rate (determined either clinically or by magnetic resonance imaging) in patients with multiple sclerosis or in patients who experienced an isolated syndrome and are at risk of developing clinically definite multiple sclerosis
    • Reduce disease severity (determined by Magnetic resonance imaging)
    • May slow progress of disability
    • Neutralizing antibodies (NAb) may develop and interfere with long-term efficacy of treatment

Immunosuppressants

  • Eg Alemtuzumab, Dimethyl fumarate, Fingolimod, Mitoxantrone, Natalizumab, Teriflunomide
  • Alemtuzumab
    • A monoclonal antibody that binds to CD52 antigen causing cell lysis
    • Recommended as a treatment option for adult patients with active relapsing-remitting multiple sclerosis
    • Studies showed a decrease in the relapse rate and risk of sustained accumulation of disability in patients
  • Dimethyl fumarate
    • A metabolite of fumaric acid that have an anti-inflammatory and anti-oxidant property that reduces oxidative cell stress
    • May be considered in patients with active relapsing-remitting multiple sclerosis
  • Fingolimod
    • Has been shown to reduce the relapse rate in patients with relapsing-remitting multiple sclerosis based on 2 large controlled trials
    • May be used as an alternative in patients with active relapsing-remitting multiple sclerosis who are intolerant of interferons and Glatiramer
  • Mitoxantrone
    • An antineoplastic agent
    • Used in patients with worsening relapsing-remitting multiple sclerosis, progressive-relapsing multiple sclerosis and secondary-progressive multiple sclerosis to reduce frequency of clinical relapse and reduce neurological disability
    • Should be reserved for patients with rapidly advancing disease who have failed other therapies
    • Probably reduces attack rate in relapsing forms of multiple sclerosis
    • Toxic effects (eg cumulative dose cardiotoxicity) may not outweigh benefit
  • Natalizumab
    • Murine monoclonal antibody used as monotherapy to prevent relapses and delay progression of disability in relapsing-remitting multiple sclerosis
    • Due to increased risk of progressive multifocal leukoencephalopathy (PML) in the use of Natalizumab, it is generally recommended for patients who had inadequate response to, or inability to tolerate alternative multiple sclerosis therapy
  • Ocrelizumab
    • An anti-CD20 monoclonal antibody approved for treatment of relapsing or primary progressive forms of multiple sclerosis
    • First B-cell targeted therapy for adult patients w/ multiple sclerosis and first drug to gain US Food and Drug Administration (FDA) approval for primary progressive multiple sclerosis
    • Efficacy of Ocrelizumab for treatment of primary-progressive multiple sclerosis was seen in a placebo-controlled clinical trial that showed risk reduction in the portion of patients with 12-week confirmed disability progression
    • Efficacy of Ocrelizumab for treatment of relapsing forms of multiple sclerosis was seen in 2 randomized double-blind active comparator trials that showed reduced annualized relapse rates and reduced worsening of disability 
  • Teriflunomide
    • Treatment option for active relapsing-remitting multiple sclerosis patients whose disease is not highly active or rapidly evolving
    • Studies show that administration of Teriflunomide significantly reduces relapse rate in patients with multiple sclerosis

Relapse Treatment

  • Goals: To reduce duration and severity of acute attacks, and reduce residual disability

Corticosteroids

  • When used short-term, has been shown to speed functional recovery in patients with acute attacks of multiple sclerosis
    • Short-term use during attacks has not been shown to give any long-term functional benefit
  • One study has shown that regular pulse glucocorticoids may be of long-term advantage to patients with relapsing-remitting multiple sclerosis, but more studies are needed
  • Methylprednisolone is used to treat acute attacks and relapses of multiple sclerosis
    • Inhibits inflammatory cascades and the activation and invasion of T cells into the central nervous system

Muscle Relaxants

  • Along with physiotherapy, muscle relaxants are one of the mainstays of management of spasticity
  • Eg Baclofen, Dantrolene, Eperisone, Tizanidine, Tolperisone
  • These drugs act via different mechanisms:
    • Baclofen is thought to act at the spinal cord level but may have supraspinal sites of action and is a powerful neuronal depressant and may exert its inhibitory effects by acting as agonist at gamma aminobutyric acid (GABA) receptors
    • Dantrolene acts directly on the muscles, possibly by interfering with the release of calcium from muscular sarcoplasmic reticulum needed for contraction
    • Eperisone is a centrally acting muscle relaxant which may also have a vasodilator action
    • Tizanidine is a centrally acting relaxant and alpha-adrenergic agonist thought to act at spinal and supraspinal levels by inhibiting the presynaptic activity of excitatory interneurons
      • It may produce additive effects to Baclofen, allowing a reduction in the dosage of both drugs
    • Tolperisone is also a centrally acting muscle relaxant

Non-Pharmacological Therapy

Gingko Biloba

  • Various evidence have shown that gingko biloba intake helps relieve fatigue but is ineffective for improvement of cognitive function

Magnetic Therapy

  • Found effective in reducing fatigue in relapsing-remitting multiple sclerosis
  • Further studies are needed to prove efficacy of magnetic therapy in reducing multiple sclerosis-related disabilities

Neurologic Deficit Rehabilitation

  • Multidisciplinary assessment by experts
  • Programs which are goal-oriented; needs of the individual will change over time so goals will need to be adjusted
  • Comprehensive management will involve:
    • Input from a number of modalities
    • Patient education and provision of information
    • Therapy from many different disciplines, including drug therapy

Plasmapheresis

  • Should be considered only in rare cases of relapse that do not respond to intravenous corticosteroids
  • Not recommended for chronic Primary-Progressive Multiple Sclerosis or Secondary-Progressive Multiple Sclerosis

Reflexology

  • May provide temporary reduction of multiple sclerosis-related paresthesia

Symptomatic Therapy

 Syptomatic Therapy

  • Patients tend to suffer from a range of symptoms
  • Symptoms change over time; constant re-evaluation is needed
  • Management needs to be individualized
  • Consider the impact of treatment of one particular symptom on the other symptoms

Therapy Goals

  • Improve function
  • Ease discomfort
  • Prevent secondary complications and disability
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