Multiple Sclerosis

Question 1

Define multiple sclerosis

Answer 1

inflammation that leads to myelin destruction and causes clinical symptoms such as motor, sensory and cognitive dysfunction

Question 2

Multiple sclerosis: most commonly affected population

Answer 2

Women between the ages of 20 and 30

(M:F = 1:2)

Question 3

In which parts of the world is multiple sclerosis incidence the highest?

Answer 3

• Highest incidence in Northern Europeans
• Lowest incidence in blacks and Asians

(The farther you go from the equator, the more incidents)

Question 4

Virus that increases the risk of multiple sclerosis

Answer 4

EBV

(no association with Hep B vaccine & MS)

Question 5

Bacteria that increases risk of MS

Answer 5

Chlamydia

Question 6

Risk factors associated with MS

Answer 6

1. Smoking (increases risk by 1.5xs & makes it worse)
2. Low vitamin D
3. Genetics: HLA-DR B1

Question 7

What is the risk of the average person developing multiple sclerosis?

Answer 7

1 in 750 (0.1%)

Question 8

What is the risk of developing multiple sclerosis when a first-degree relative has it?

Answer 8

Absolute risk < 5%

Question 9

What is the risk of developing Multiple sclerosis if your twin has it?

Answer 9

• Monozygotic 31%
• Dizygotic 5%

Question 10

What genetically has shown to be associated with the risk of MS

Answer 10

HLA-DR2 (chromosome 6)

(no commercial test available)

Question 11

What are the three pathological processes that take place in multiple sclerosis (in order)?

Answer 11

1. Inflammation
2. Demyelination
3. Axon loss

Question 12

Describe the inflammatory process of multiple sclerosis?

Answer 12

Inflammatory cytokines cause the passage of and activation of inflammatory cells into the brain parenchyma

(break down in the BBB)

Question 13

Describe the demyelination process of multiple sclerosis pathology

Answer 13

Activated Th1 cells will lead to the activation of microglial cells and immune cells to attack myelin and a oligodendrocytes and destroy the myelin on the axon

(axonal demyelination → death of axon; they ball up and cause plaques)

Question 14

Types of multiple sclerosis (4)

Answer 14

1. Clinically isolated syndrome
2. Relapsing-remitting (RRMS)
3. Secondary Progressive (SPMS)
4. Primary Progressive (PPMS)

Question 15

Multiple sclerosis: CSF findings

Answer 15

1. IgG index
2. Oligoclonal bands

Question 16

Multiple sclerosis: differential diagnosis (9)

Answer 16

1. migraine (most common)
2. NSWMD (nonspecific white matter disease)
3. small vessel ischemic dz
4. psych issue
5. NMO
6. fibromyalgia
7. Radiologicaly isolated syndrome
8. spondylopathy
9. neuropathy

Question 17

How long do patients with multiple sclerosis carry a misdiagnosis for on average? What are they usually diagnosed with first?

Answer 17

• 3-9 years (30%) & 10-20 years (26%)
• migraine→ fibromyalgia→abnormal MRI→psychogenic→NMOSD (neuromyelitis optic spectrum disorder)

Question 18

Multiple sclerosis: ocular manifestation (3)

Answer 18

1. Optic neuritis
2. Afferent pupillary defect
3. Diplopia - INO

(INO = inter-nuclear ophthalmologic)

Question 19

Multiple sclerosis: MRI findings

Answer 19

• White matter lesions (signs of aging)
• Black holes & progressive cases

Question 20

What are some clinical features that are noted not to be suggestive features of MS?

Answer 20

1. steady progression
2. onset before age 10 or after age 50
3. cortical deficits such as aphasia, apraxia, alexia, neglect
4. rigidity, sustained dystonia
5. convulsions
6. early dementia
7. deficit developing within minutes

Question 21

White matter lesions differential diagnosis (5)

Answer 21

1. toxic/metabolic issues
2. inflammation
3. infection
4. trauma
5. hereditary leukodystrophy

Question 22

what are some prevalent causes of periventricular white matter abnormalities found in people over 65?

Answer 22

1. lyme dz
2. SLE
3. MS
4. vascular causes (small vessel)

(also normal aging)

Question 23

What 4 areas of the CNS does MS typically involve?

Answer 23

1. corpus callosum
2. temporal lobes
3. brainstem/cerebellum
4. spinal cord* 90% in MS (rare in normal aging and small vessel dz

Question 24

Describe the MS lesions seen on MRI.

Answer 24

only a couple of segments

(BBB opens up & the T cells rush in → lesions; then they regress)

Question 25

Evoked potentials | (for MS dx)

Answer 25

measuring how fast the sensory nerves transmit signal ???????

Question 26

3 routes of admin for MS meds?

Answer 26

1. injections 2. oral 3. infusions

Question 27

Rx for MS

Answer 27

Tysabri (reduces lesions, slows disability & relapse rate)

Question 28

4 Clinically isolated syndrome sx

Answer 28

1. ON 2. transverse myelitis 3. brainstem syndrome 4. cerebellar syndrom

Question 29

Brainstem syndrome (3 sx)

Answer 29

1. diplopia 2. face numbness/weakness 3. dysarthria

Question 30

CIS or MS attack tx in ER (4)

Answer 30

1. abx 2. spinal tap 3. IgG 4. oligoclonal banding (OCB) 5. IVMP (????)

Question 31

Goals of MS tx

Answer 31

reduce MRI activity (also slow disease, relapse, maintain adherence)

Question 32

How do you follow MS patients disease progression?

Answer 32

yearly MRIs

Question 33

Biomarkers for MS (4) indicating a change in Rx

Answer 33

1. Ab to IFN 2. Aquaporin-4 (for neuromyelitis optica) 3. Myelin oligodendrocyte glycoprotein (MOG) 4. JC virus Abs

Question 34

Rx for MS w/JC Virus

Answer 34

Tecfidera | (maybe tysabri 12 months)

Question 35

3 Clinical indicators of MS progression

Answer 35

1. continued attacks w/meds 2. new lesions 3. relapses

Question 36

Primary Progressive MS Tx (PPMS)

Answer 36

Ocrevus

Question 37

Secondary progressive MS (SPMS)

Answer 37

immunosuppression (IVIG, plasma exchange, bone marrow transplant)

Question 38

SPMS w/attacks Tx (4)

Answer 38

1. Tecfidera 2. Tysabri 3. Mavenclad 4. Mayzent

Question 39

What can make MS symptoms worse (2)

Answer 39

1. heat 2. infection

Question 40

Neuromyelitis optica tx

Answer 40

Rituxan | (other immunosuppressants)