(3.2) Pathophysiology of multiple sclerosis

Question 1

What are common sxs of MS?

Answer 1

• Visual problems; e.g. monocular blindness (optic nerve), double vision
• Numbness, tingling (often an early symptom)
• Fatigue, motor weakness (corticospinal tract)
• Difficulty walking, gait problems, falls; ataxia (cerebellum)
• Pain (sensory pathways)
• Spasticity (stiffness, involuntary muscle spasms)
• Dizziness, vertigo (vestibular pathways)
• Sexual dysfunction
• Bladder problems, constipation
• Emotional or cognitive changes; depression

Question 2

What are less common sxs of MS?

Answer 2

• Tremors, seizures
• Itching (pruritis), feeling of pins and needles
• Speech and swallowing issues
• Breathing problems (chest muscles affected by nerve damage)
• Headache
• Hearing loss

Question 3

What is the potential role of viral infections in the etiology of MS?

Answer 3

Viral or bacterial infections may increase the risk of MS by activating autoreactive immune cells, leading to autoimmune response in genetically susceptible individuals

Question 4

What evidence supports the viral infections causing MS mechanism?

Answer 4

• Increase IgG synthesis in CNS of MS pts
• Increased antibody titers to certain viruses
• Epidemiological data suggesting childhood infection increases MS risk

Question 5

What specific virus may be involved in developing MS?

Answer 5

Epstein-Barr Virus

Question 6

What regarding sequences may be the reason why EBV could cause MS?

Answer 6

Sequence similarities between EBV and self-peptides result in activation of autoreactive T or B cells (molecular mimicry)

Question 7

What increases the concentration of Epstein-Barr nuclear antigen (EBNA) in MS pts?

Answer 7

Increased antibody

Question 8

Which individuals have an increased risk of developing MS?

Answer 8

Individuals w a particular HLA phenotype when they also have anti-EBNA antibodies (illustrates gene-environment interactions)

Question 9

What are the different clinical forms of MS?

Answer 9

Question 10

How prevalent is relapsing-remitting MS (RRMS)?

Answer 10

About 85% of cases

Question 11

What is involved with RRMS?

Answer 11

Involves relapses of neurological dysfunction lasting weeks or months and affecting the brain, optic nerves, and/or spinal cord

Question 12

How is damage of RRMS found?

Answer 12

Multifocal areas of damage are revealed by magnetic resonance imaging, generally (but not always) in white matter

Question 13

What characterizes RRMS?

Answer 13

Initial sxs disappear, but less remission w each relapse

Question 14

What happens w most cases of RRMS?

Answer 14

Most cases of RRMS eventually enter a phase of SPMS

Question 15

What characterizes secondary progressive MS (SPMS)?

Answer 15

• Characterized by less inflammation than RRMS
• Involves slow progressive neurological decline and CNS damage, w little remission

Question 16

How prevalent is primary progressive MS (PPMS)?

Answer 16

About 15% of cases

Question 17

What does PPMS resemble?

Answer 17

Resembles SPMS at initial stage of disease

Question 18

What differentiates PPMS to RRMS?

Answer 18

Mean age of onset is later than RRMS perhaps bc inflammatory episodes of RRMS surpass the symptomatic threshold

Question 19

What characterizes clinically isolated syndrome (CIS) of MS?

Answer 19

• an initial episode of neurological sxs lasting >= 24h
• involves inflammation and demyelination in optic nerve, cerebellum, cerebrum, brainstem, or spinal cord (one or more foci)
• most cases progress to MS

Question 20

Pathophysiology of MS figure that will be on exam. Memorize.

Answer 20

• Progressive phase involves cytodegeneration (loss of myelin, axons, oligodendrocytes) and occurs with a similar rate in different forms of MS (thick blue line)
• The overall clinical presentation is determined by combination of underlying degeneration (uniform, progressive) and the host’s immune rxns to it (intermittent, variable) (dashed blue/orange lines)

Question 21

Explain the autoimmune phase of MS.

Answer 21

• Antigens released from CNS OR cross reactive foreign antigens are presented to B and T cells in lymph nodes
• B and T cells w high affinity receptors for these antigens are expanded and migrate to CNS sites where they re-encounter and are activated by their target ligands
• Activated B and T cells then carry out immune functions (release of antibodies and cytokines) at the CNS sites

Question 22

Explain the degenerative phase of MS.

Answer 22

• CNS damage is triggered by activated B and T cells or by other insults such as infection or stroke
• Antigens released from damaged sites in the CNS further prime immune cells in periphery, thus completing a vicious cycle

Question 23

Which of the two MS phases triggers the disease?

Answer 23

It is unclear

Question 24

What is Guillian-Barre Syndrome?

Answer 24

• Acute, inflammatory neuropathy
• Occurs in all parts of the world, affects children and adults of all ages and both sexes
• Preceded by a GI or respiratory infection in about half of pts

Question 25

What are the sxs of Guillain-Barré syndrome?

Answer 25

• Weakness that begins in distal muscles and lower extremities, ascends to proximal muscles and upper extremities
• Can progress to total paralysis w death from respiratory failure in days

Question 26

Generally, how long does it take for Guillain-Barré syndrome to peak?

Answer 26

Progression peaks at 10-14 days

Question 27

What is the pathophysiology of Guillain-Barré syndrome?

Answer 27

Autoimmune attack on peripheral nerves by circulating antibodies, resulting in demyelination

Question 28

What are the txs of Guillain-Barré syndrome?

Answer 28

• Ventilation (in cases of respiratory difficulty)
• Plasmapheresis (to eliminate auto-antibodies)
• IV immunoglobulin administration

Question 29

What is the prognosis of Guillain-Barré syndrome?

Answer 29

• Recovery is slow (months to a year)
• Fatalities can result from respiratory failure or infection
• Most surviving pts (95%) recover completely, and remainder have minor motor deficits

Question 30

What is the key step where remyelination fails in MS?

Answer 30

OPC differentiation