71. MS/Demyelinating Disease

Question 1

MS

• epidemiology
• genetics
• geography
• environmental factors

Answer 1

• onset age 20-50, W>M (3:1)
• genes: has HLA DRB*1501, missing HLA AO2 (protective effect)
• geography: more common near poles (more temperate environments)
• environment: EBV/infectious mono, low vitamin D, tobacco smoke exposure, youth obesity, born in Springtime

Question 2

What are signs of active MS lesions on pathology?

What are signs of remyelination following inflammation?

Answer 2

Path: hypercellularity, perivascular infiltrate from lymphocytes, widespread myelin damage (looks pale), myelin fragment-laden macrophages, axonal damage

RM post-inflammation: oligodendrocyte precursors migrate to lesion, thinner/shorter myelin segments, “shadow plaques” of intermediate myelin staining intensity

Question 3

How does MS appear in MRI imaging of the brain? What are the 3 types of appearances?

Answer 3

Type 1 Lesion - at grey-white junctions in brain
Type 2 Lesion - scattered small lesions in deep gray cerebral cortex (seen on path only)
Type 3 Lesion - superficial cortex with overlying meningeal inflammation by B lymphocytes and microglial activation

Question 4

What is the pathogenesis/pathophysiology of MS?

Answer 4

Inflammatory Component:

• Relapsing MS: CNS lymph infiltration (naive thymic T Cells sensitized to epitopes outside CNS, autoreactive T cells come into CNS and get reactivated, local CNS inflammation = more inflammatory cell infiltrates)
• B cells play role as APCs and immune regulators
• Innate immune system activated (more microglia)
• toxic intermediates from immune effector cells DAMAGE axons, neurons, oligodendrocytes

Non-Inflammatory Component:
Progressive damage from mito. injury, Glu Excitotoxicity, Oxidative stress, energy fialure

Question 5

What is the pathophysiology of Axonal Damage in MS?

Answer 5

Axon demyelination = new Na channels put up to maintain conduction = more energy needed to main ion gradients = metabolic stress, energy failure = axon destruction

Loss of myelin = exposed to toxic mLc in microenvironment

Question 6

What is the clinical presentation of MS?

Answer 6

BROAD RANGE OF SX, none unique to disease
Sensory: numbness, burning in body/face
Vision: monocular vision blurring/loss, impaired color vision, scotoma, diplopia, INO, afferent pupillary defect
Motor: weakness, spasticity
Coordination: ataxia, dysarthria, dysphagia, incontinenge
Cerebral: fatigue, depression, cognitive impairments

Question 7

Difference between Relapsing-Remitting MS and Progressive Onset MS?
What are triggers for an MS pseudo-exacerbation?

Answer 7

RRMS: 90% pts, acute transient neuro sx

POMS: 10% pts (rarer), gradually worsening neuro impairement, with SC sx (relapses may occur)

Trigger: heat, fatigue, fever, other illness (considered pseudo-exacerbation if recovery by cooling/rest)

Question 8

What is the Dx criteria for MS (3)?

Answer 8

1. DIT (time): CNS inflammatory demyelination events occurring at different times
2. DIS (space): events in multiple locations within CNS
3. Exclusion of other conditions that better explain disease process

Question 9

What are some examples of acute CNS demyelinating events?

Answer 9

1. Optic Neuritis - monocular vision loss, pain with eye movement
2. SC inflammation
3. Brainstem/Cerebellar Attacks (diplopia, coordination)
4. Hemispheric Lesions

Question 10

What does MS look like on MRI? CSF? Conduction speed tests?

Answer 10

MRI: “Dawson’s fingers” - lesions near ventricle following cerebral veins

CSF: unique oligoclonal CSF bands, active Ig production in CSF

CS: slowing in pathways consistent with MS

Question 11

Neuromyelitis Optica Spectrum Disorder

• what is it
• key test
• mechanism

Answer 11

inflammation of optic nerve, brain, sc
M: antibody against AQP channels = astrocytopathy = SECONDARY demyelination via inflammation
Dx antibody: NMO-AQP4 IgG

Question 12

Anti-MOG Antibody Disease

• what is it
• Dx

Answer 12

PRIMARY Demyelinating disease (antibodies target MOG on oligodendrocytes)

Dx: Anti-MOG antibodies

CP: optic neuritis/myelitis

Question 13

Acute Disseminated Encephalomyelitis

• what is it
• dx
• tx

Answer 13

in peds populations, preceding infection/vaccination

dx: LARGE enhancing lesion on MRI + AMS/seixure/HA
tx: IV steroids, plasma exchange

Question 14

types of MS tx

• disease modifying
• sx tx
• acute relapse tx

Answer 14

DMT: Ocrelizumab (+20 agents) - decrease future events and mitigate further CNS damage; also tx modifyable risk factors
SxTx: accommodate/mitigate impairments to optimize fx
ART: High dose STEROIDS, Plasma exchange (speed up recovery)

Strategy: early initation of DMT at dx, individualized agent/pt selection, monitor evidence of activity, and switch meds if inadequate response