Multiple Sclerosis

Question 1

MS definitions and presentations

Answer 1

• autoimmune de-myelination liaisons of CNS white matter (not PNS matter)
• lesions (plaques) are multi focal (2 or more)
• localization: any level of the CNS

Question 2

Complaints of MS

Answer 2

Wide range of deficits on initial or recurring attacks

Question 3

Temporal profile of MS

Answer 3

• onset can be acute, but typically subacute or insidious

- course: typically episodic or cyclic, relapse-remitting, can become chronic and progressive

Question 4

Diagnosis of MS

Answer 4

Starts with history and neuro exam evidence for 2+ lesions in CNS

Question 5

OD significance of MS

Answer 5

• MS is often preceded by transient episode of optic neuritis (visual loss)
• MS often involves visual, pupillary, or oculomotor deficits
• importance of recognizing that seemingly in-related deficits could be MS

Question 6

Pathogensis of MS

Answer 6

-small breaches of BBB (possibly triggered by microglia) or blood CSF barrier (in choroid plexus) allow lymphocytes into CNS, followed by an AI attack involving damage to oligodendrocyte

Question 7

Original hypothesis on specific mechanism of MS

Answer 7

• Ab against Myelin Basic Protein

- T cells release cytokines toxic to oligodendrocyte

Question 8

Secondary tissue changes in MS

Answer 8

• following oligodendrocyte damage/death, macrophages attack debris and myelin sheath.
• astrocytes form glial scar around zone of damage
• axons can survive in non-myleinated state, or there can be axonal damage as well

Question 9

Distribution of MS

Answer 9

Multi-focal

-evidence for 2 or more focal lesions in the CNS

Question 10

Temporal profile of MS

Answer 10

1. 2 or more attacks separated by > 1m apart or

2. Chonric and progressive lasting at least 6 months

Question 11

Complaints in MS

Answer 11

• visual, cognitive, psychiatric, motor, sensory, pain
• visual system: visual loss localizing from optic disc to visual cortex
• mental status: cognitive impairments, psychiatric symptoms
• cranial nerves: motor, sensory deficits, vertigo, pupillary dysregulation
• motor systems: weakness, fatigue, impaired coordination/balance
• sensory systems: generally sensory loss, also parenthesia/pain
• autonomic dysfunction: bladder, bowel, sexual

Question 12

Common presentations of MS with optometric significance

Answer 12

• history of optic neuritis episode
• pupillary constriction of dilation deficits, horners syndrome
• EOMS: nerve palsies, conjugate gaze palsy, internuclear ophthalmoplegia

Question 13

Common precursor to MS

Answer 13

Optic neuritis

Question 14

____ of patients with optic neuritis later develop MS

Answer 14

50%

Question 15

Inflammatory de-myelination of the optic nerves

Answer 15

Optic neuritis

Question 16

Etiology of optic neuritis

Answer 16

1. Inflammatory process triggered during or after resolution of viral infection
2. Pro inflammatory chemical exposure
3. Vitamin B12 deficiency

Question 17

Onset of optic neuritis

Answer 17

Typically 30-45 years, but can be later

Question 18

Gender and optic neuritis

Answer 18

2x more likely in females

Question 19

Visual loss due to optic neuritis

Answer 19

Usually monocular vision loss, central scotoma, reduced acuity around scotoma, impaired color detection, can be complete monocular vision loss

Question 20

OD exam for optic neuritis

Answer 20

Depends on whether inflammation extends to optic disc or is limited to retro-bulbar segment of optic nerve. Thus, optic disc can be swollen and inflamed or normal. Prior episodes can lead to optic disc pallor

Question 21

Exacerbating or precipitating factors for optic neuritis

Answer 21

Infection
Heat or over heating (VF deficits especially sensitive) 
Dehydration 
Sleep deprivation
Anemia 
Dietary factors

Question 22

Heat induced transient vision loss

Answer 22

Uthoff phenomenon

Transiently induced by hot bath

Question 23

Temporal profile of optic neuritis

Answer 23

1. Cyclic/episodic, relapse-remitting

2. Chronic and progressive, aka “primary progressive MS”

Question 24

Less severe outcomes of MS

Answer 24

If 1st attack had an acute onset, few types of symptoms/signs, predicts rapid/complete remission. More likely to follow relapse-remitting course. Caveat to “less severe” prediction: relapse-remitting patient’s can potentially develop secondary progression MS where plaques become permanent lesion sites

Question 25

More severe outcomes of MS

Answer 25

If 1st attack was more gradual (subacute or insidious), multiple functional systems affected, spinal cord involvement, more at risk for primary progressive MS

Question 26

Epidemiology of MS

Answer 26

- 1:1000 - 2x more in females - 20-40y - more common in caucasians, especially in higher latitude regions - genetic risk: siblings 2.6% risk, more in twins - mutations in IL-2 and IL-7 possibly

Question 27

Diagnostic criteria for MS

Answer 27

- MRI evidence or 2 or more plaques in white matter - Evoked potential findings: reduced conduction velocity - CSF analysis by electrophoresis: “oligoclonal bands”

Question 28

MRI of 2 or more white matter plaques in MS

Answer 28

- plaques can be supratentorial, infratentorial, or in spinal cord - often appear as fingers extending from periventricular zones - MRI with contrast (gadolinium) can highlight plaques - plaques can heal or can stabilize and become permanents lesions

Question 29

Evoked potentials for MS

Answer 29

Reduced conduction velocity (increased latency) | -visual, auditory, or somatosensory evoked potentials

Question 30

CSF analysis by electrophoresis in MS

Answer 30

Oligoclonal bands - increased protein, increased IgG, normal or increased lymphocytes - elevated lymphocytes: up to 50 cells per ul - oligoclonal bands refers abnormal bands at specific molecular weights - bands-large amounts of same immunoglobulin (IgG) being produced - 85% sensitivity for MS - 92% specificity for MS

Question 31

Short term treatment for MS

Answer 31

For acute attack (Rapid onset) - glucocorticoids: methylprednisone or prednisone - rapid and potent immunosuppressive strategy

Question 32

Long term treatment for MS: 1st line

Answer 32

Interferon 1-beta - increases suppressor T cells systemically - decreases lymphocytes invasion of CNS across barriers - decreases inflammatory cytokines from T cells - decreases antigen presentation mechanisms

Question 33

Long term treatment for MS: 2nd line

Answer 33

Being developed - off-label use of chemotherapies to reduce lymphocyte proliferation - targeting enzymes in lymphocytes to reduce proliferation, invasion, inflamamtion - monoclonal Ab to neutralize lymphocyte-mediated inflammation - Ab of mature oligodendrocyte from glial stem cells, increasing oligodendrocytes

Question 34

Differential Dx in MS

Answer 34

Overlap among MS and other neuoimmunological and demyelinating diseases - neuromyelitis optica - acute disseminated encephalmyelitis (ADEM) - progressive multifocal leukoencephaolopathy

Question 35

Neuromyelitis optica as a DiffDx for MS

Answer 35

AI disease involving Ab against aquaporin-4. Lesion localization is specifically combination of optic nerve and spinal cords. Multi focal and stable

Question 36

Acute dissemination encephalomyelitis (ADEM) as DiffDx for MS

Answer 36

AI mechanism triggered by recent infection or VAx, attacks against gray matter as well as whit matter, rapid onset of neuro signs, initally focal or multifocal signs then diffuse localization/ distribution. Can be stable or remission

Question 37

Progressive multifocal leukoencephalopathy as diffdx for MS

Answer 37

Viral infection of the CNS that evidently most affects oligodendrocytes. Chronic progressive course of white matter damage/lesions