Post on 25-Dec-2015
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Multiple Sclerosis
• Inflammatory demyelinating disease of the central nervous system.
• Most common cause of neurological disability in young adults.
Multiple Sclerosis
• Epidemiology:940 patients followed at the multiple sclerosis clinic of the Montreal Neurological Institute:
Multiple Sclerosis
• Epidemiology:• Sex ratio: F:M = 1.77:1.00
• Prevalence ranges from <5 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
Multiple Sclerosis
• Temporal patterns• Relapsing-remitting (RR) MS: 55%
• Secondary progressive (SP) MS: 31%
• Primary progressive (PP) MS: 9%
• Progressive relapsing (PR) MS: 5%
Multiple Sclerosis
• Pathophysiology:– Consequences of demyelination:
• Slowing of conduction
• Conduction block
• Uhthoff’s phenomenon – Temperature
• Mechanical stimulation
Multiple Sclerosis
• Pathophysiology:– Axonal injury
• Usually occurs later, but also evidence of early loss.
Multiple Sclerosis
• Pathophysiology:– Recovery:
• Early – Resolution of oedema, cytokines, pH
• Intermediate – Increase in internodal Na channels
• Later – Remyelination
Multiple Sclerosis
• Pathophysiology:– Immunological disease:
• Complex, not fully elucidated, various patterns.
• Disruption of perivenular BBB.
• Migration of T cells (CD8+CD4) 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.
Multiple Sclerosis
• Clinical features:– Cranial nerve deficits:
• Optic neuritis – common• Oculomotor involvement:
– Isolated nerves: VI>III>IV– Internuclear ophthalmoplegia– Nystagmus
• Trigeminal neuralgia• Facial palsy, but Taste not affected.• Hemifacial spasma and myokemia• Pseudobulbar palsy – common in later stages
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.
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
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 > fecal incontinence
• Sexual dysfunction
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
Multiple Sclerosis
• Clinical features:– Characteristic positive features:
• Lhermitte’s phenomenon - Electric shock radiating down the spine or into the limbs on flexion of the neck.
• Uhthoff’s phenomenon – Worsening of existing symptoms
• Trigeminal neuralgia, central pain, paraspinal spasms, myokemia, phosphenes and a variety of other paroxysmal neurological symptoms.
Multiple Sclerosis• Diagnostic Criteria: Revised McDonald et al. (2005) Diagnostic Criteria for Multiple Sclerosis
CLINICAL (ATTACKS)
OBJECTIVE LESIONS ADDITIONAL REQUIREMENTS TO MAKE DIAGNOSIS
2 or more 2 or more None. Clinical evidence alone will suffice; additional evidence desirable but must be consistent with MS
2 or more 1 Dissemination in space by MRI or 2 or more MRI lesions consistent with MS plus positive CSF or await further clinical attack implicating other site
1 2 or more Dissemination in time by MRI or second clinical attack
1 1 Dissemination in space by MRI or 2 or more MRI lesions consistent with MS plus positive CSF AND dissemination in time by MRI or second clinical attack
0 (progression from onset)
1 or more Disease progression for 1 year (retrospective or prospective) AND 2 out of 3 of the following:
Positive brain MRI (9 T2 lesions or 4 or more T2 lesions with positive VEP)
Positive spinal cord MRI (2 or more focal T2 lesions)
Positive CSF
Multiple Sclerosis• Diagnostic Criteria:
– Positive MRI = 3 or more:
1 gadolinium-enhancing brain or cord lesion or 9 T2 hyperintense brain and/or cord lesions if there is no gadolinium-enhancing lesion
1 or more brain infratentorial or cord lesions
1 or more juxtacortical lesions
3 or more periventricular lesions
Note: Individual cord lesions can contribute along with individual brain lesions to reach required number of T2 lesions.
Multiple Sclerosis• Diagnostic Criteria:
– MRI EVIDENCE OF DISSEMINATION IN TIME :
A gadolinium-enhancing lesion detected in scan at least 3 months after onset of initial clinical event at a site different from initial event- or -A new T2 lesion detected in a scan done at any time compared to a reference scan done at least 30 days after initial clinical event
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.
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)
Multiple Sclerosis
• Treatment:– Disease modifying treatment in SP and PRMS:
• Mitoxanthrone
• Interferon beta-1b (Betaferon)
• Cyclophosphamide ??
• Azathioprine ??
• Methotrexate ??
• Monthly – 3 monthly pulses of Solumedrol ??