Inflammatory Disorders

Question 1

Relapse-remitting MS (RRMS)

Answer 1

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

Question 2

Primary Progressive MS (PPMS)

Answer 2

15% of MS patients; slow progression of symptoms from the outset, variable rate

Question 3

Secondary Progressive MS (SPMS)

Answer 3

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

Question 4

Progressive-Relapsing MS (PRMS)

Answer 4

1% of MS; characterized by a combination of relapses and progression from the outset

Question 5

Clinically Isolated Syndrome (CIS)

Answer 5

Can be diagnosed by MRI after a single, first “attack”

Question 6

Radiologically Isolated Syndrome (RIS)

Answer 6

Diagnosed in patients with apparent MS on MRI scans but without clinically apparent MS symptoms

Question 7

Multiple Sclerosis - Epidemiology

Answer 7

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

Question 8

MS - Neuropathology

Answer 8

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

Question 9

MS - Genetic Risks

Answer 9

Associated with HLA-DR2

IL-7 and IL-2 receptor mutations

Question 10

MS - Environmental Risks

Answer 10

EBV - risk of MS in EBV-negative individuals is near zero

Vitamin D deficiency

Obesity

High salt diet?

Question 11

MS - Diagnosis

Answer 11

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

Question 12

MS - Early symptoms

Answer 12

Onset is most often unifocal:

Numbness/tingling
Loss of vision 
Gait/balance problems 
Weakness
Diplopia 
Urinary urgency and frequency 
Constipation
Vertigo

Question 13

MS - Late symptoms

Answer 13

Multifocal, more generalized Sx:

Fatigue
Sexual dysfunction 
Cognitive dysfunction
Depression
Spasticity
Dysphagia

Question 14

Hydrocephalus ex vacuo

Answer 14

Enlargement of cerebral ventricles in compensation for brain parenchyma atrophy; not the result of increased CSF pressure

Question 15

Negative prognostic features of MRI in MS

Answer 15

Atrophy
Posterior Fossa Lesions
Spinal Cord lesions
High Burden of T1 Holes

Question 16

CSF Evaluation in MS

Answer 16

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

Question 17

“Benign” vs. “Malignant” MS

Answer 17

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

Question 18

MS Treatment - Acute Attacks

Answer 18

High dose, short burst steroids (IV with oral taper)

Plasma Exchange for severe attacks unresponsive to steroids

Question 19

MS Treatment - Immunomodulation Agents (#)

Answer 19

Interferon beta-1a
Interferon beta-1b
Glatiramer Acetate

Require home injection; approved for RRMS

Question 20

Natalizumab

Answer 20

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

Question 21

MS treatment - Approved Oral Agents

Answer 21

Fingolimod
Dimethyl Fumarate
Teriflunomide