Neuropathology Flashcards
Identify the main causes of possible classifications of pathology.
INHERITED
• Genetic
ACQUIRED
• Infections (e.g. viruses, bacteria, other)
• Inflammation (e.g. vasculitis, paraneoplastic, idiopathic, MS) • Toxic (e.g. drugs, chemicals etc)
• Metabolic (e.g. DM, vitamin deficiency, thyroid problems etc) • Degenerative (idiopathic)
• Trauma
• Other
What are the main problems of relying on pathology ?
- Sampling error (may sample the wrong portion of tissue e.g. non-malignant part of brain, not inflamed part of neuron)
- Accessibility of tissue (not easy to access brain tissue)
- Often tissue only available late in disease process (i.e. post-mortem)
To what extent does diagnosis of AD and PD depend on neuropathology ?
NOT, neither uses biopsies in life. Instead, relies on clinical symptoms and imaging.
In AD, can only be certain for the diagnosis using neuropathology but POST-MORTEM.
What is the role of oligodendrocytes ? How metabolically active are they ? How much myelin does each oligodendrocyte produce?
Producing myelin which allows saltatory conduction to occur.
VERY metabolically active, so very susceptible to damage by processes, including inflammatory processes.
Each oligodendrocyte produces between 30 and 60 sections of myelin.
How many layers of myelin may we find around an axon ?
20-30
Describe the timeline of Multiple Sclerosis. Which of these steps does most treatment for MS target ?
- Occurs in episodes (e.g. initial, episode of clinical problem such as optic neuritis)
- If recurrent, diagnosis of relapsing remitting MS
- If not, diagnosis of isolated syndrome
- With time, get recurrent inflammation due to breakdown of BBB (with time, accumulation of disability, cannot get to same level as before episode)
- After year, majority of patients go on to secondary progression (slow deterioration, particularly in walking distance, possible use of one stick then two sticks then wheelchair, then at some point decrease in function stops)
Most treatment targets first phase of RR in 20s-30s with frequent inflammation and demyelination, not secondary progression (no treatment for that phase)
Describe the neuropathology of MS.
- Inflammatory cells entering brain parenchyma, and attacking myelin, oligodendrocytes, causing demyelination
- Initial BBB breakdown leads to demyelination
- After time, most patients will get some degree of recovery, which is thought to be due to repair of BBB
- Shadow plaques appear where areas of myelin redeposition are slightly thinner (due to re-myelination of axons following acute episode of demyelination)
- Breakdown of BBB then causes further, recurrent inflammation (hence get scarring, which makes re-myelination much more difficult + overgrowth of astrocytes) (with inflammation, also get transection of nerve fibers, and death of nerve cells, as well as supportive cells, leading to shrinkage of CNS)
- Dawson fingers are a feature of demyelination characterized by periventricular demyelinating plaques distributed along the axis of medullary veins, perpendicular to the body of the lateral ventricles and/or callosal junction. This is thought to reflect perivenular inflammation.
-Post-mortem brain of MS, brain is hard where plaques have formed
How does optic neuritis present as an episode of MS ?
Painful, visual loss in young person (may start with complete blindness), with loss of color vision, and gradual recovery
Do all episodes of inflammation associated with MS manifest clinically ?
No, episodes of inflammation only manifest when in certain areas (e.g. affecting the eye) or when very severe
e.g. if episode of inflammation on frontal lobe may not know about
Describe epidemiology of relapsing-remitting MS.
Tends to occur in 20s-30s
F:M 3 or 4:1
Describe the pathology behind secondary progression of MS.
Lots of episodes of inflammation underlying condition, and some axonal loss that gradually continues throughout the course after a very short period of time (axonal loss thought to underlie secondary progression)
Identify a type of MS besides RR. What are the main differences between RR and this ?
Primary progressive:
- Gradual reduction of walking distance and gradual deterioration of function
- Tends to be equal in sex incidence
- Tends to occur in slightly older age group than RR, 40s or 50s (compared to 20s-30s for RR)
- Affects less people than RR (10-15%)
Graph amount of brain V, inflammation, and axonal loss in different stages of MS.
Refer to slide 2 in page 4
What proportion of MS patients have a RR diagnosis ? What proportion of MS patients go on to secondary progression ?
45% RR
30% SP
Describe epidemiology of MS.
- Tends to occur in 20s-30s
- Affects women more than men
To what extent does MS have a genetic component ?
Twin studies show that rate of MS for monozygotic twins is 1/3 as opposed to 1/30 for dizygotic twins. Hence, strong genetic element though not fully genetic (otherwise would be 100% for monozygotic twins).
What is the role of the genes involved in MS ?
Most have role in control of immune system.
Biggest defect comes from region in chromosome 6 (MHC)
Identify environmental factors involved in development of MS.
VITAMIN D
• Vitamin D deficiency and susceptibility to MS Prospective studies have shown that vitamin D deficiency prior to MS onset predisposes individuals to increased risk of MS; modulated by geography and sunlight
• Vitamin D levels also affect rate of relapses in RRMS: For every 10ng/mL increase in baseline vitamin D level there was a 34% decrease in rate of subsequent relapse
• Why: Vitamin D as an immunomodulator
EBV INFECTION
SMOKING
-Confers a 1.5x risk
To what extent does vitamin D supplementation decrease disease activity ?
Unsure if supplementation with vitamin D decreases disease activity
