Multiple Sclerosis

Question 1

Definition: a chronic inflammatory disease of the CNS characterized by ___ __ or __ neurologic symptoms due to __, __ and __ degeneration

Epi: average age of onset is 32, (which gender is affected more?), worldwide 1:3000; Canada 1:400

Answer 1

Definition: a chronic inflammatory disease of the CNS characterized by relapsing remitting or progression neurologic symptoms due to inflammation, demyelination and axonal degeneration

Epi: average age of onset is 32, F>M, worldwide 1:3000; Canada 1:400

Recall that non-pain neurons are more myelinated than pain neurons. Therefore, this demyelinating disease is more likely to affect myelinated axons, indicating that motor skills tend to be more affected in MS than pain.

Question 2

MS is a __ and ___ disorder. The continuous __ of ___ and neurons is believed to be the principal contributor to progression of disability in MS.

How does inflammation play a role in the degeneration process of MS

Answer 2

DEMYELINATING and DEGENERATIVE disorder. The continuous loss of axons and neurons is believed to be the principal contributor to progression of disability in MS.

INFLAMMATION CAUSES PLAQUES

Inflammatory: immune cells (T-cells primarily) activated in periphery enter the CNS to destroy oligodendrocytes + myelin (demyelinating). The immune cells enter the CNS through post-capillary venules, meninges and choroid plexus

Inflammation of both white and gray matter drives neuropathology

The MS lesions= plaques (loss of oligodendrocytes + myelin)

In addition to inflammatory cells, glutamate, free radicals, mitochondrial dysfunction/energy insufficiency, iron toxicity, proteases, hypoxia also contribute to mechanisms of injury

Question 3

In addition to inflammation, what other factors contribute to the neuropathology of MS?

Answer 3

In addition to inflammatory cells, glutamate, free radicals, mitochondrial dysfunction/energy insufficiency, iron toxicity, proteases, hypoxia also contribute to mechanisms of injury

Question 4

Classic sign on CT that may indicate MS

Answer 4

Active Plaque: where demyelination is ongoing in the presence of cellular infiltrates (inflammatory cells, T cells, macrophage and microglia)–> may see central vein sign: specific for MS and can be seen in active lesions

Question 5

Protective factors and risk factors of MS

Answer 5

Risk Factors: smoking, later in life EBV exposure, vit D def, high BMI in adolescence, lack of exercise in childhood, concussion in adolescence, night shift work, changes in the microbial composition of the intestinal compartments.

Protective: sunlight, vit D, coffee/fish intake

Question 6

Which gene confers the highest signle risk of MS

Answer 6

• Environment: see risk factors above
• Genetics: accounts for 30% of risk. If identical twin 1:3; fraternal 1:15, sib 1:25

Over 200 genetic loci implicated, _HLA-DRB1 *1501 confers highest single risk._

Question 7

First (and possible only attack) in a person’s life time–> what kind of subtype?

Answer 7

clinically isolated syndrome

(almost always has ocular manifestations)

Question 8

diagnostic criteria and gender that relapsing remitting MS causes

Answer 8

Relapsing remitting (RRMS): 85% of all new cases, requires 2 attacks to diagnose, 3F:1M

Question 9

Is there a gender difference in cases of primary progressive symptoms

Answer 9

Primary progressive (PPMS): 10% of all new cases, F=M, average age 45yo

“No relapses,” only steady progression of disability.

Question 10

T/F there are relapses in PPMS

Answer 10

false. this is primary progressive– it just continues to get worse. there are no relapses or good/bad days

Question 11

secondary progressive is the “second step “ that 50-70% of __ cases become

Answer 11

50-70% of relapsing remitting cases become SPMS

Question 12

DDx for MS

Answer 12

vascular: multiple strokes

migraines

infections: HIV, lyme
tumor: space occupying lesions
metabolic: vit B12 def, hypothyroid
inflammatory: acute demyelinating encephalomyelitis, sarcoid, SLA, neuromyelitis optica spectrum

Question 13

DDx for MS

Answer 13

vascular: multiple strokes

migraines

infections: HIV, lyme
tumor: space occupying lesions
metabolic: vit B12 def, hypothyroid
inflammatory: acute demyelinating encephalomyelitis, sarcoid, SLA, neuromyelitis optica spectrum

Question 14

Symptoms of MS are broad because symptom presentation depends on lesion location. some can even be clinically silent. Some symptoms include numbness, visual disturbance, weakness, spasticity, diplopia, impaired gait, vertigo, bladder dysfunction

E|Which two condition/symptoms can happen in 80% oc ases?

Answer 14

bladder dysfunction and eye movement abnoramlities can haooen in 80% of cases.

• optic nueritis can happen in 50% in the first 5 years.

Question 15

Is MS UMN or LMN

Answer 15

it often causes lesion in the BRAIN so it can manifest a lot in UMN

Spasticity can happen in 90% of cases

Question 16

Compare and contrast acute and chronic MS pain

Answer 16

acute MS pain: trigeminal neuralgia, optic neuitis, injection sites reaction

chronic MS pain: neuropathic pain (burning, electric, shooting), band-like tightness, deep aching pain (spasticity)

Question 17

Mcdonald criteria for diagnosing RRMS

Answer 17

symptoms need a dissemination in time and space

Dissemination in time: 2 attacks at two different points in time

§ 2nd episode must occur >30d after 1st relapse

§ New lesion must appear on MRI >30d after 1st relapse

Dissemination in space: 2 different clinical symptoms due to lesions in 2 CNS locations

§ MRI lesions must be characteristic location for an MS lesions

Question 18

Mcdonald criteria for diagnosing PPMS

Answer 18

McDonald Criteria: for diagnosing PPMS

1 year of progressive symptoms with at least 2 of…

>2 spinal cord lesions

>1 lesion in the brain in a characteristic location

Oligoclonal bands/increased protein in the CSF

Question 19

demyelinating plaques appear as ___ lesions on T2 weight MRI.

What are characteristics locations of MS lesions?

What are characteristics of MS lesions in general?

Answer 19

appear as HYPERDENSE LESIONS on T2 weigth MRI

• MS lesions are usually located periventricular, Juxtacortical/cortical, brainstem, cerebellum, spinal cord

Characteristics of MS lesions: ovoid, well-circumscribed, oritented perpendicular to lateral ventricles.

Question 20

What two characteristics of CSF analysis would indicate PPMS

Answer 20

oligocloncal pans and elevated protein

Question 21

anti-aquaporin4 antibodies are characteristic of ___ ____ spectrum disorder

Answer 21

neuromyeltiis optica spectrum disorder

Question 22

general labs for MS

Answer 22

Labs: ANA, ENA, ESR, HIV, TSH, vitB12, CSF analysis (elevated protein and oligoclonal bands), anti-aquaportin4 antibodies (for neuromyelitis optica spectrum disorder)

Question 23

T/F you should wait for symptoms to get to a certain point before you treat MS

Answer 23

false. treatment shoud be started ASAP.

TREAT EARLY→ steroids (1250 prednisone q2d x5) or IVIG (if steroids are not tolerated)

Treatment shortnes time to recovery, but no evidence to suggest it changes extent of recovery.

CIS: minocycline→ conversion from CIS to MS was lowered from 61% to 33% by minocycline

Question 24

key medication that has been seen to have effects in CIS

Answer 24

TREAT EARLY→ steroids (1250 prednisone q2d x5) or IVIG (if steroids are not tolerated)

Treatment shortnes time to recovery, but no evidence to suggest it changes extent of recovery.

CIS: minocycline→ conversion from CIS to MS was lowered from 61% to 33% by minocycline

Question 25

1st, 2nd and 3rd line prevention

Answer 25

1st line: vitamin D, smoking cessation, disease modifying theapy (teriflunomide, interferon-beta, glatiramer acetate)

2nd line: natalizumab, fingolimod

Avoid EBV

Question 26

what medication class might help with cognition to improve short term memory?

Answer 26

L-amphetamines

Question 27

Factors in addition to MS that can contribute to brain atrophy

Answer 27

Control atrophy from other causes: cardiovascular disease, diabetes, poor sleep, obesity, depression, alcohol use, dehydration

Mediterranean tired found decreased rate of relapses and decrease in T2 lesions.

MIND diet: leady greens, nuts, berries, beans, whole grains, fish, poultry, olic oil and wine.