Inflammatory Disorders Flashcards
Relapse-remitting MS (RRMS)
85% of all MS patients (50% eventually convert to secondary progressive MS)
Sporadic episodes of new or worsened symptoms and signs lasting 2-10 days, with variable improvement over 1-6 months
Primary Progressive MS (PPMS)
15% of MS patients; slow progression of symptoms from the outset, variable rate
Secondary Progressive MS (SPMS)
Majority of RRMS converts to progressive disease; patients begin with a relapsing course but go on to develop steadily more progressive disease with fewer, if any, relapses over time
Progressive-Relapsing MS (PRMS)
1% of MS; characterized by a combination of relapses and progression from the outset
Clinically Isolated Syndrome (CIS)
Can be diagnosed by MRI after a single, first “attack”
Radiologically Isolated Syndrome (RIS)
Diagnosed in patients with apparent MS on MRI scans but without clinically apparent MS symptoms
Multiple Sclerosis - Epidemiology
3/4 present between 15-45 years of age; 2/3 or more are women; highest incidence is in Caucasians
Most common inflammatory CNS disease
MS - Neuropathology
Demyelination of axons
Axonal loss - formation of axon bulbs (acute and chronic)
Perivascular lymphocytic infiltrate
Lymph node-like structures (with B and T cells) in meninges
MS - Genetic Risks
Associated with HLA-DR2
IL-7 and IL-2 receptor mutations
MS - Environmental Risks
EBV - risk of MS in EBV-negative individuals is near zero
Vitamin D deficiency
Obesity
High salt diet?
MS - Diagnosis
Presence of multiple CNS lesions disseminated in space and time + objective abnormalities on neurological exam
RRMS - 2 or more clinical attacks 30+ days apart
PPMS - Minimum 12 months of progression of Sx, with disseminated lesions in space
MS - Early symptoms
Onset is most often unifocal:
Numbness/tingling Loss of vision Gait/balance problems Weakness Diplopia Urinary urgency and frequency Constipation Vertigo
MS - Late symptoms
Multifocal, more generalized Sx:
Fatigue Sexual dysfunction Cognitive dysfunction Depression Spasticity Dysphagia
Hydrocephalus ex vacuo
Enlargement of cerebral ventricles in compensation for brain parenchyma atrophy; not the result of increased CSF pressure
Negative prognostic features of MRI in MS
Atrophy
Posterior Fossa Lesions
Spinal Cord lesions
High Burden of T1 Holes
CSF Evaluation in MS
Elevated IgG CSF levels in comparison to blood (by IgG index)
Oligoclonal banding - IgG bands seen in CSF but not serum
Protein and WBC are usually normal or mildly elevated
Glucose is normal
“Benign” vs. “Malignant” MS
Without treatment:
10-20% have “benign MS” with rare attacks and little disability
5% have “malignant MS,” which is rapidly progressive; patients become wheelchair bound within 5 years, bed bound within 10 years
MS Treatment - Acute Attacks
High dose, short burst steroids (IV with oral taper)
Plasma Exchange for severe attacks unresponsive to steroids
MS Treatment - Immunomodulation Agents (#)
Interferon beta-1a
Interferon beta-1b
Glatiramer Acetate
Require home injection; approved for RRMS
Natalizumab
Humanized monoclonal antibody to alpha-4 integrin; blocks ability of activated lymphocytes to enter CNS through BBB endothelium
Provides a 70% reduction in relapse rate over 2 years - this is 2x better than first line agents; BUT, increases risk of progressive multifocal leukoencephalopathy (PML), a rare brain infection caused by reactivation of the JC virus
MS treatment - Approved Oral Agents
Fingolimod
Dimethyl Fumarate
Teriflunomide
