(3.2) Pathophysiology of multiple sclerosis Flashcards
What are common sxs of MS?
- 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
What are less common sxs of MS?
- Tremors, seizures
- Itching (pruritis), feeling of pins and needles
- Speech and swallowing issues
- Breathing problems (chest muscles affected by nerve damage)
- Headache
- Hearing loss
What is the potential role of viral infections in the etiology of MS?
Viral or bacterial infections may increase the risk of MS by activating autoreactive immune cells, leading to autoimmune response in genetically susceptible individuals
What evidence supports the viral infections causing MS mechanism?
- Increase IgG synthesis in CNS of MS pts
- Increased antibody titers to certain viruses
- Epidemiological data suggesting childhood infection increases MS risk
What specific virus may be involved in developing MS?
Epstein-Barr Virus
What regarding sequences may be the reason why EBV could cause MS?
Sequence similarities between EBV and self-peptides result in activation of autoreactive T or B cells (molecular mimicry)
What increases the concentration of Epstein-Barr nuclear antigen (EBNA) in MS pts?
Increased antibody
Which individuals have an increased risk of developing MS?
Individuals w a particular HLA phenotype when they also have anti-EBNA antibodies (illustrates gene-environment interactions)
What are the different clinical forms of MS?
How prevalent is relapsing-remitting MS (RRMS)?
About 85% of cases
What is involved with RRMS?
Involves relapses of neurological dysfunction lasting weeks or months and affecting the brain, optic nerves, and/or spinal cord
How is damage of RRMS found?
Multifocal areas of damage are revealed by magnetic resonance imaging, generally (but not always) in white matter
What characterizes RRMS?
Initial sxs disappear, but less remission w each relapse
What happens w most cases of RRMS?
Most cases of RRMS eventually enter a phase of SPMS
What characterizes secondary progressive MS (SPMS)?
- Characterized by less inflammation than RRMS
- Involves slow progressive neurological decline and CNS damage, w little remission
How prevalent is primary progressive MS (PPMS)?
About 15% of cases
What does PPMS resemble?
Resembles SPMS at initial stage of disease
What differentiates PPMS to RRMS?
Mean age of onset is later than RRMS perhaps bc inflammatory episodes of RRMS surpass the symptomatic threshold
What characterizes clinically isolated syndrome (CIS) of MS?
- 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
Pathophysiology of MS figure that will be on exam. Memorize.
- 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)
Explain the autoimmune phase of MS.
- 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
Explain the degenerative phase of MS.
- 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
Which of the two MS phases triggers the disease?
It is unclear
What is Guillian-Barre Syndrome?
- 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
What are the sxs of Guillain-Barré syndrome?
- 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
Generally, how long does it take for Guillain-Barré syndrome to peak?
Progression peaks at 10-14 days
What is the pathophysiology of Guillain-Barré syndrome?
Autoimmune attack on peripheral nerves by circulating antibodies, resulting in demyelination
What are the txs of Guillain-Barré syndrome?
- Ventilation (in cases of respiratory difficulty)
- Plasmapheresis (to eliminate auto-antibodies)
- IV immunoglobulin administration
What is the prognosis of Guillain-Barré syndrome?
- 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
What is the key step where remyelination fails in MS?
OPC differentiation
