Demyelinating diseases and multiple sclerosis

Question 1

Acquired and genetic CNS demyelinating diseases

Answer 1

• Multiple sclerosis (MS)
• MS variants such as devics (neuromyelitis optics)
• Transverse myelitis
• Optic neuritis
• Progressive multifocal leukoencephalopathy (JC virus)
• Non-inflammatory metabolic diseases
• Genetic metachromatic leukoencephalopathy (MLD), adrenoleukoencephalopathy (ALD), and krabbe leukodystrophy (KLD)

Question 2

Multiple sclerosis

Answer 2

• Chronic disabling disease of an autoimmune attack on the CNS (brain, SC, optic nerves) only
• 3:1 incidence for women, highest incidence in caucasians
• Age of onset 25-50
• Approx. 400,000 in US, 1:1000 incidence rate

Question 3

Temporal course of MS

Answer 3

• Pre-clinical phase: before any symptoms begin
• CIS (clinically isolated syndrome)
• Relapsing remitting MS (RRMS)
• Secondary progressive MS (SPMS)

Question 4

Immunopathogenesis and pathology of MS

Answer 4

• Inflammation that is characteristic of MS can result in regeneration of damaged nerves, but can also lead to degeneration if too much damage is done
• Characterized by inflammation, demyelination, and axonal loss
• We can only Rx the inflammation but not any of the other Sx
• If the damage is not very severe, only myelin is lost (can be repaired)
• If the damage is severe the axon is severed and the neuron is lost (cannot be repaired)

Question 5

Clinical manifestations of MS

Answer 5

• Fatigue, pain, numbness, weakness, spasticity
• Optic neuritis, sexual, bowl, bladder dysfunction
• Can result in paralysis

Question 6

Dx of MS

Answer 6

• Abnormal neurologi exam
• White plaques on MRI (in white matter) and optic neuritis
• Evoked visual and somatosensory potentials
• CSF w/ evidence of inflammation (increases IgG and oligoclonal bands)
• Fluctuating Sx after acute event
• Demyelination of axons and destruction of axons histologically

Question 7

Glatiramer acetate

Answer 7

• Shifts to Th2 response (from Th1)
• Down regulates Th1
• Reduces relapse rate
• Induces activation of Treg

Question 8

Interferon B1

Answer 8

• B1a: reduces relapse rate, development of MRI lesions, slows lesion growth, prevents atrophy of brain and possibly delays progression
• B1b: reduces relapse rate, may delay progression, slows lesion growth
• Both are neutralizing Abs

Question 9

Mitoxantrone

Answer 9

• Reduces attach rate in RRMS
• Also used in SPMS b/c appears to have effect on disease progression
• Many side effects

Question 10

Tysabri

Answer 10

• Most effective for RRMS
• Reduces acute attacks and formation of new MRI lesions
• Does increase risk of developing PML

Question 11

Gilenya

Answer 11

• First oral Rx, prevents lymphocyte egress form secondary lymphoid tissue (produces lymphopenia)
• Many side effects but effective in RRMS

Question 12

Aubagio

Answer 12

• X rated for pregnancy
• Similar to glatiramer
• Side effects: liver and hair loss (related to chemo)

Question 13

Tecfidera

Answer 13

-Few side effects, efficacy like gilenya