6. Neuropathology 2 Flashcards
How are neuropathologies classified?
- Inherited (genetic) or 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
Problems of relying on pathology
- Sampling error
- Accessibility of tissue
- Often tissue only available late in disease process (i.e. post-mortem)
Vitamin D and MS
- vitamin D deficiency prior to MS onset predisposes individuals to increased risk of MS
- Vitamin D as an immunomodulator
Which disease are MS patients of?
EBV
(Due to high level in general pop)
Virtually all subjects with MS (>99%) are infected with EBV compared to only ~90% of control subjects.
In ALS there is degeneration of..
- Cortico-spinal tracts
- Hypoglossal nuclei of medulla
*Dorsal column preserved
Parkinson’s disease pathology
Lewy-body presence in dopaminergic pathway of substantia nigra
Prion diseases
Related to abnormal prion protein.
Pathology of Alzheimer’s disease
Presence of tangles and plaques
Initial presentation of peripheral neuropathy
Numbness spread up from feet/hands due to axonal or demyelinating degeneration
Causes of peripheral neuropathy?
Diabetes (*scotland) Leprosy (* world) Idiopathic (*clinic) Toxic-alcohol, drug Vit def Post inefction (Guillain-barre syndrome)
Other name for inherited peripheral neuropahties?
Presentation
Charcot-Marie-Tooth
Presentation:
- Distal wasting
- Inverse champagne bottle legs
- Sensitive to trauma
Contractile Properties
• Slow twitch (I) fibers innervated by _____ 2 motor neurons, smaller of the two α motor neurons
• Fast twitch (II) fibers innervated by alpha 1 motor neurons, ____ of the two α motor neurons
• Fast twitch (II) fibers have _____ excitation threshold and faster conduction velocity
Contractile Properties
• Slow twitch (I) fibers innervated by alpha 2 motor neurons, smaller of the two α motor neurons
• Fast twitch (II) fibers innervated by alpha 1 motor neurons, larger of the two α motor neurons
• Fast twitch (II) fibers have higher excitation threshold and faster conduction velocity
Motor unit recruitment?
• Motor neurons recruited in order of size: Size Principle
• Smallest alpha motor neurons, α2, which belong to slow twitch recruited first
• Largest alpha motor neurons, α1, which belong to fast twitch recruited last
09/11/2017
Difference in staining properties of alpha type I and II fibres?
- Slow twitch (type I) have myosin isoforms with low ATPase activity.
- Fast twitch (type II) have myosin isoforms with high ATPase activity that promotes rapid breakdown of ATP for energy of high-speed muscle shortening.
Difference in distribution properties of alpha type I and II fibres?
- All muscle composed of ST & FT fibers
- Distribution varies from muscle to muscle within an individual
- Most individuals possess between 45 and 55% ST
Muscle biopsy:
Done under?
Which muscles?
What investigation done first?
- Usually done under LA
- Usually deltoid, quadriceps or tibialis anterior (often muscle & nerve)
- Usually have done CPK and EMG first
Which muscles diseases are inherited?
- **Dystrophies (degen & regen) **
- Congential myopathies (no regen)
- Mitochondrial
- Metabolic
- Myotonic
Which muscle diseases are acquired?
- Inflammatory (polymyositis/dermato)
- Toxic (e.g. alcohol, simvastatin)
- Metabolic (e.g. Cushing’s)
- Disuse atrophy
- Rhabdomyolysis
Epidemiology of dystrophies?
Usually boys as X linked genetic mutation
Life expectancy <20yrs
Female carriers can do slight muscle weaknesses
Dominance: X linked recessive inheritance
In MS appearance on T2 MRI scan?
White spots at the corpus callosum
Punched out lesion of BS = area of demyelination
What is MS?
Multiple sclerosis (MS) is a chronic inflammatory autoimmune demyelinating disease of the central nervous system. 4 types: -Relapsing remitting MS (RRMS) -Secondary progressive MS (SPMS) -Primary progressive MS (PPMS) -Progressive relapsing MD (PRMS)
What is MS?
Multiple sclerosis (MS) is a chronic inflammatory autoimmune demyelinating disease of the central nervous system.
Pathophysiology: Activated immune cells invade the central nervous system and cause inflammation, neurodegeneration and tissue damage.
4 types:
- Relapsing remitting MS (RRMS)
- Secondary progressive MS (SPMS)
- Primary progressive MS (PPMS)
- Progressive relapsing MS (PRMS)
MS symptoms?
Changes in vision (unilateral visual loss, diplopia) Weakness Dyscoordination Sensory loss or distortions Changes in bowel and bladder function
Impact of MS on BBB
- In multiple sclerosis, the blood-brain barrier is damaged or weakened in some way (e.g. INFLAMMATION) and immune cells are able to CROSS.
- These cells attack the myelin around nerves, causing DEMYELINATION which leads to MS symptoms.
What does the radiological sign of “Dawson’s fingers” imply?
Dawson fingers are a radiographic feature depicting demyelinating plaques through the corpus callosum, arranged at right angles along medullary veins (callososeptal location). They are a relatively specific sign for multiple sclerosis (MS), which presents as T2 hyperintensities.
Scarring in MS due to…
Astrocyte cells in healing process
Eventually leads to nerve cell death
Prediction of MS onset?
Unpredictable
Usually around 30yrs
Progression of MS?
Most early sclerois is relapsing and remitting then later progresses to secondary progressive
Over time diminished capacity to repair Increased axonal loss Progression —> 2ndary progressive phase of MS At this point this is little to do clinically (symptoms control)
- Frequent inflammation, demyelination, axonal transection, plasticity of remyelination
- Continuing inflammation, persistent demyelination
- Infrequent inflammation chronic axonal degeneration, gliosis
Concordance of MS in twins
Monozygotic twins have 30% concordance rate
Dizygotic is 4%
Why? It’s a POLYGENIC DISEASE
