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Risk Factors, Previous episode of gait unsteadiness and urinary…
Risk Factors
26 years old
MULTIPLE SCLEROSIS
T cell mediated damage
Demyelination
MRI with contrast
Multiple periventricular white matter lesions of differing ages (some asymptomatic)
Newer lesions are brighter (gadolinium-enhancing)
High T2 signal in retrobulbar left optic nerve
Dissemination over space
Optic neuritis
Colour desaturation
Eye pain on movement of left eye
Damage to optic nerve
Impaired transmission of light information to pretectal nucleus and then Edinger-Westphal nucleus
Loss of input to oculomotor nerve for pupillary light reflex
Relative afferent pupillary defect
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Impaired visual acuity of left eye
Central visual field deficit of left eye
Central scotoma in left eye
Confrontational visual field testing
Normal optic disc on fundoscopy
Abnormal VEP in left eye
Corticosteroids
VLA-4 upregulated by activated T cells
α4β1 integrin on T cells that binds to VCAM-1
T effector cells adhere to endothelial cells
T cells migrate to areas of inflammation
Natalizumab (monoclonal antibody for VLA-4)
Risk of developing PML if JCV positive
S1P allows activated T cells to leave lymph nodes
Migrate to CNS
Fingolimod (S1PR agonist)
Traps T cells in lymph nodes (acts as functional antagonist)
B cell antibody mediated damage
Ocrelizumab
binds to CD20
CSF gel electrophoresis
CSF-restricted oligoclonal bands present
Alemtuzumab
binds to CD52
Act as APCs to activate T cells
Teriflunomide
inhibits dihydrooratate dehydrogenase
Cladribine
Toxic to dividing and nondividing lymphocytes
Interferons
Suppress inflammatory responses
controls secretion of pro and anti-inflammatory cytokines
suppress T cell activation
induce differentiation of neural stem cells to oligodendrocytes
Female
Lived in Sweden (high latitude) until 17
Mild upper respiratory infection 2 weeks ago
Genetic predisposition
Previous episode of gait unsteadiness and urinary incontinence
Dissemination over time
Diagnosis of MS (McDonald's criteria)
Prodromal phase
8.5 TBL MECHANISTIC DIAGRAM
Gerry Guo, Kara Harris, Mohammed Hassan, Christy Hou & Daniel Kasunic