Multiple Sclerosis

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Multiple Sclerosis
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Multiple Sclerosis

• Inflammatory demyelinating disease of the central
  nervous system.
• Most common cause of neurological disability in
  young adults.

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Multiple Sclerosis

• Epidemiology
• 940 patients followed at the multiple sclerosis
  clinic of the Montreal Neurological Institute

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Multiple Sclerosis

• Epidemiology
• Sex ratio FM 1.771.00
• Prevalence ranges from lt5 to 60 per 100 000.
  Higher in Europe and North America.
• South Africa White population 5-25/100 000.
• Genetics Sibs 3-5 risk. Monozygotic twins
  20-38 risk

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Multiple Sclerosis

• Temporal patterns
• Relapsing-remitting (RR) MS 55
• Secondary progressive (SP) MS 31
• Primary progressive (PP) MS 9
• Progressive relapsing (PR) MS 5

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Multiple Sclerosis

• Pathophysiology Demyelination

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Multiple Sclerosis

• Pathophysiology
• Consequences of demyelination
• Slowing of conduction
• Conduction block
• Uhthoffs phenomenon Temperature
• Mechanical stimulation

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Multiple Sclerosis

• Pathophysiology
• Axonal injury
• Usually occurs later, but also evidence of early
  loss.

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Multiple Sclerosis

• Pathophysiology
• Recovery
• Early Resolution of oedema, cytokines, pH
• Intermediate Increase in internodal Na channels
• Later Remyelination

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Multiple Sclerosis

• Pathophysiology
• Immunological disease
• Complex, not fully elucidated, various patterns.
• Disruption of perivenular BBB.
• Migration of T cells (CD8CD4) and macrophages.
• Macrophages occur in centre of lesion, associated
  with oligodentrocyte destruction and
  demyelination.
• In periphery of lesion Remyelination by
  surviving oligodendrocytes and even
  oligodendrocyte proliferation.
• Plaques Discreet areas of demyelination,
  macrophage, and T-cell infiltration,
  astrocytosis.

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Multiple Sclerosis

• Radiological features

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Multiple Sclerosis

• Clinical features
• Cranial nerve deficits
• Optic neuritis common
• Oculomotor involvement
• Isolated nerves VIgtIIIgtIV
• Internuclear ophthalmoplegia
• Nystagmus
• Trigeminal neuralgia
• Facial palsy, but Taste not affected.
• Hemifacial spasma and myokemia
• Pseudobulbar palsy common in later stages

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Multiple Sclerosis

• Clinical features
• Sensory symptoms
• Common
• Various patterns
• Often paresthesias, dysesthesias and other
  positive symptoms.
• Plaques involving dorsal root entry zones are
  common radicular pain or severe loss of
  proprioception useless hand with normal power.

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Multiple Sclerosis

• Clinical features
• Motor features
• Usually later than sensory
• Hemiparesis with cerebral or brainstem lesions
• Acute partial myelitis.
• Gradually progressive paraparesis characteristic
  of progressive forms of MS.
• Cerebellar features - common

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Multiple Sclerosis

• Clinical features
• Impairment of Bladder, Bowel, and Sexual
  Functions
• Urgency and urgency incontinence
• Dyssynergic voluntary sphincter activity
• With involvement of sacral spinal segments
  Hypotonic bladder with overflow incontinence.
• Constipation gt fecal incontinence
• Sexual dysfunction

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Multiple Sclerosis

• Clinical features
• Cognitive Impairment
• Subtle and underreported.
• Subcortical Abstract conceptualization, recent
  memory, attention, and speed of information
  processing
• Affective Disorders
• Depression 50 risk. Higher than with other
  chronic neurological diseases.
• Fatigue

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Multiple Sclerosis

• Clinical features
• Characteristic positive features
• Lhermittes phenomenon - Electric shock radiating
  down the spine or into the limbs on flexion of
  the neck.
• Uhthoffs phenomenon Worsening of existing
  symptoms
• Trigeminal neuralgia, central pain, paraspinal
  spasms, myokemia, phosphenes and a variety of
  other paroxysmal neurological symptoms.

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Multiple Sclerosis

• Diagnostic Criteria  
• Revised McDonald et al. (2005) Diagnostic
  Criteria for Multiple Sclerosis

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Multiple Sclerosis

• Diagnostic Criteria  
• Positive MRI 3 or more

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Multiple Sclerosis

• Diagnostic Criteria  
• MRI EVIDENCE OF DISSEMINATION IN TIME

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Multiple Sclerosis

• Prognosis
• Poor prognostic indicators
• Male
• Older onset
• Progressive from start
• Frequent initial relapses
• Pyramidal or brainstem rather that optic neuritis
  or sensory symptoms.
• Pure optic neuritis, without brain lesions has
  good prognosis, only 16 progress to MS in 5
  years. Compared to 51 with 3 lesions.

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Multiple Sclerosis

• Treatment
• Acute attacks Methyl-Prednisolone 500mg to
  1000mg daily x3-5/7.

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Multiple Sclerosis

• Treatment
• Disease modifying treatment in RRMS
• Interferon beta-1a (Avonex) 30ug IMI/w
• Interferon beta 1a (Rebif) 22-44ug SC 3x/w
• Interferon beta-1b (Betaferon) 8MIU alt days
• Glatirimer acetate (Copaxone) 20mg daily
• Mitoxanthrone
• Natalizumab (Tysarbi)

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Multiple Sclerosis

• Treatment
• Disease modifying treatment in SP and PRMS
• Mitoxanthrone
• Interferon beta-1b (Betaferon)
• Cyclophosphamide ??
• Azathioprine ??
• Methotrexate ??
• Monthly 3 monthly pulses of Solumedrol ??

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Multiple Sclerosis

• Treatment
• Disease modifying treatment in PPMS
• ???