MS Flashcards
MS characteristics: general overview
most prevalent chronic inflammatory CNS disease
punctuated by fully or partially reversible episodes of neurologic
disability, usually lasting days or weeks
Autoimmune disorder
* But with neurodegenerative component
Myelin is attacked in the white matter
* But also in the gray matter
Axonal damaged in the brain and spine
* But loss of oligodendrocytes and
neuronal cell bodies as well
Gross Pathology and Histopathology of MS Lesion (how it is seen in images)
Darkened tissue seen in brain slices is due to scaring
- stain for myelin, less stained = less myelin, more stained = more myelin
staining for immunological cells, there are some inside the lesion and outside, a dense area of immunological cells (microglia) AROUND the lesion
Limits of technology
Higher tesla unit = you can see more lesions =
there are probably lesions that we also cannot see in these images because they cannot be picked up
Also we cannot determine whether damage remains in an image taken at the recovery timepoint
Lesions on MRI and Progression: T2FLAIR vs T1
concept of sensitivity
T2-FLAIR to detect WM lesions in MS patients (even the less severe damage)
T1 as its less sensitive to detecting lesions you can only see the most severe damage
Gadolinium Enhancement, Relapse and Recovery
Gadolinium enters where there is increased disruption of the BBB
(i.e more porous blood vessels)
Gadolinium:
> Shows an active new lesion and hasn’t gone to the extent where there is extensive/severe WM damage as you cannot see it in the plain T1 image and only in the gadolinium T1 image
> If image cannot be seen on new MRI at recovery time point: The acute inflammatory phase has passed, the BBB has come back together. Cannot determine whether the damage remains
What is the BBB
The BBB is blood vessel walls and choroid plexus (produces the CSF))
Are Lesions Restricted to the White Matter?
Ring of microglia is also seen in cortical tissue so damage is NOT only in WM
Brain Atrophy in MS
MS patient might have faster brain atrophy than HC
Ventricles become larger because you lose brain matter so ventricles expand as they fill with CSF
Diagnosis of MS
Usual diagnostic considerations: lumbar puncture, MRI (WM, brain + spinal atrophy)
CSF markers: Oligoclonal bands indicate CNS-restricted immune response.
Optical coherence tomography (OCT) assesses retinal thinning, correlating with brain atro
Lumbar puncture: draws out CSF to measure a sign of antibodies
Look for:
- dissemination in space (DIS, e.g lesion in optic nerve, in spinal cord, in brain)
- dissemination in time (DIT, e.g lesions occurring at different times)
DIT can be done in one visit to the hospital by using T2-FLAIR, T1, T1 + gadolinium:
- See if there’s new lesions forming based on which lesions you can see in which sequence and which are old lesions
- Gadolinium damage seen may be so new that you can’t see it on T2-FLAIR
Symptoms of MS
Early symptoms include:
Optic neuritis (monocular vision loss)
Transverse myelitis (limb weakness, sensory loss)
Brainstem dysfunction (double vision)
Cerebellar lesion (ataxia)
Disease typically progresses to impaired mobility, cognition, and bladder control.
> fatigue, tingling/numbness, vertigo etc
Disease Subtypes: old thinking vs new
Progression can be indepdendent of relapse
> a significant portion of disease worsening happens without traditional relapse events
> cognitive decline occurring independently of relapse events
RRMS
SPMS
PPMS
PRMS
Treatment
Mechanism is to lower immune activity in the brain
> but this increases risk of infections
Prevalence
more in women
life expectancy close to normal
Northern europe / america
20-40 yrs old
pathology and lesions
Focal demyelination, inflammation, and glial reaction (activation of glial cells (astrocytes, microglia, and oligodendrocytes) in response to CNS damage, leading to inflammation, scar formation, sometimes repair)
Lesion evolution depends on:
Immune activity
Age of the patient (younger individuals show better repair)
Remyelination capacity
Genetic & Environmental Risk Factors
Genetic: HLA DRB1*1501 haplotype is the strongest risk factor.
Family history: First-degree relatives have 2–4% risk (higher risk)
Environmental factors:
Higher latitude → More MS cases (linked to sunlight/vitamin D)
Epstein–Barr virus (EBV) and mononucleosis increase risk.
Smoking and obesity are risk factors.
Immune System Involvement
T cells (CD4+, CD8+) and B cells play key roles
B-cell depletion therapies (e.g., ocrelizumab) are highly effective
Microglia and macrophages contribute to inflammation and repair
Blood-brain barrier disruption is an early event in lesion formation.
