Degeneration and Dementia Flashcards
What are the three main forms of neuronal degeneration?
1) Wallerian –> distal degeneration of both the axon and myelin, usually trauma induced.
2) Axonal –> degeneration of the axon towards the cell body (some regeneration is possible)
3) Demyelination –> loss of oligodendrocytes or schwann cells, affecting conduction velocity. Central form –> multiple sclerosis Peripheral form –> Guillian Barre
What are some of the common causes of Wallerian degeneration?
Generally head trauma, causing diffuse axonal injury - where you get widespread shearing of axons from their cell bodies, damage to white matter tracts and grey matter.
Shaken baby syndrome (coup- contre coup injury), and nerve compression.
What are the three classes of wallerian degeneration?
Neuropraxia –> least severe, stretching injury rather than shearing, neuronal cell body and axon remain intact. (praxia = inaction)
Axontmesis –> moderate damage to neuronal axon/ myelin, but remain intact (tmesis = to cut)
Neurotmesis –> most severe, partial or complete severing/ shearing of neuronal cell body and axon. (tmesis = to cut)
After a wallerian degenerative injury is regeneration possible?
Regeneration is possible but depends on the type of cut, clean cut better than twisting/ ripping.
Depends exactly on GF’s, proteins and amount of electrical activity of the injured neuron.
Peripheral NS is better than the CNS at regeneration as Schwann cells are better at releasing GF’s than oligodendrocytes.
What is transneural degeneration and why might it occur?
Transneural degeneration is degeneration of the neurons that synapse with the primarily injured neuron.
It occurs as injury to 1 neuron means loss of communication to the other neurons which die by the “use it or lose it” principle.
What are amyloid plaques?
What proteins are involved and what conditions are these proteins associated with?
Amyloid plaques are aggregrates of misfolded protein or fragmented protein.
Proteins involved: Beta amyloid –> alzheimers
Alpha synuclein –> in parkinsons
prions –> CJD
Tau proteins –> alzheimers and parkinsons
How might amyloid plaques be caused?
- Amyloid plaques are caused by misfolded or fragmented proteins
- this can be caused by a change in phsophorylation or changes in protein folding
- Leads to increased Beta sheet formation
What are neurofibrilary tangles?
What protein is involved?
What is the normal function of this protein and how is this changed in disease?
- Neurofibrilary tangles are formed by misfolded Tau protein that forms long strips and fibrils that group together to become a tangle.
- Tau is a microtubule associated protein that normally functions to stabilised the structure of MT’s and is involved in the transport of vesicles down microtubules to the synapse, where Tau stabilises vesicles being held there.
- In disease, hyperphosphorylation of Tau proteins leads to misfolding of the Tau protein. Misfolding of the Tau protein leads to:
- Get loss of structural integrity of microtubules/ breakdown
- loss of vesicle transport and neuronal signalling
- leading to cell death.
What are inclusions? What is included under this term?
What are the proteins normally involved?
What other proteins can be involved?
What is the characteristic appearance of inclusions?
- Inclusions are intracellular protein aggregations formed of misfolded proteins
- Includes both Lewy bodies and Pick cells (also pick bodies- formed of large, dark protein aggregations).
- Protein involved is mainly alpha synuclein
- other proteins that can be involved = ubiquitin, crystallin, neurofilament
- Characteristic appearance = dense core and halo of surrounding filaments
What is diabetic neuropathy?
How does it present?
What is the cause?
- Diabetic neuropathy is where you get degeneration in neurones due to microvascular disease. Insufficient blood supply to neurons leading to axonal degeneration that heads towards the cell body.
- Primarily axonal –> dying back
- It can affect peripheral, autonomic or central nerves
- If peripheral it is often symmetrical and has a glove and stocking appearance –> starts in peripheries first, affecting feet, knees then fingers.
- Affects regions with poorest circulation first.
- Presents with pain both neurological and nociceptive (ulcer formation).
- Neurological pain presents with tingling and poor balance.
What is motor neurone disease?
How can it present?
Who does it affect more?
What is the mean survival?
- Motor neurone disease is a rare neurological condition that causes the degeneration of the motor system, leading to muscle weakness and wasting. There are no sensory signs, bladder or ocular involvement.
- Regions of degeneration affects the presentation of the disease which can present with both UMN and LMN symptoms, bulbar and pseudobulbar features and muscle weakness/ atrophy. Degeneration can occur in:
- Corticospinal and pyramidal tracts –> primary lateral sclerosis = progressive muscle weakness in voluntary muscles, affecting UMN
- Motor cortex itself
- Corticobulbar pathways (pseudobulbar palsy)
- Cranial nerve nuclei (progressive bulbar palsy)
- Anterior horn cell (progressive muscle atrophy)
- Unknown cause but affects men > women
- Mean survival is only 3 years
What is amyotrophic lateral sclerosis?
What is the cause? Where does degneration occur?
How may it present/ what are its particular features?
what is the life expectancy?
Amyotrophic lateral sclerosis (also known as Lou gehrig’s disease), describes a progressive neurological degenerative condition that affects the motor pathways specifically involved in the control of voluntary muscles.
- Caused by change in SOD1 - superoxide dismutase that breaks down ROS that cause neuronal damage.
- Leads to degeneration of motor neurons in corticospinal tract (Betz cells) and neurons in anterior horn. Thinning of anterior roots and fibres pathways.
- Characterised by:
- Gliosis –> increase in glial / supporting cells following damage
- Astrocytosis –> increase in astrocytes following neuronal damage
- degeneration of corticospinal tract
- muscle atrophy
- Presents with Tonic atrophy –> muscle atrophy, fasiculations, hypereflexia
- Life expectancy only 2-6 years.
What is Friedrich’s ataxia?
What is the inheritance pattern? What is the cause?
How does it present?
- Friedrich’s ataxia is an autosomal recessive inherited disorder that affects the Frataxin gene, affecting Iron metabolism.
- This leads to degeneration of large myelinated neurons, spinocerebellar tracts, dorsal columns, dorsal root ganglia and eventually loss of cerebellar mass and corticospinal tracts.
- Presents with:
- Progressive limb and gait ataxia
- Sensory ataxia
- Loss of proprioception, joint position and vibration senses
- Loss of tendon reflexes lower limb
- muscle weakness
- cardiomyopathy
- Dysmetria –> over or undershoot of movement
- Dysarthria –> difficult/ unclear articulation of speech
What is Guillain Barre syndrome?
What is the trigger?
How may it present?
What forms are there?
How is it treated?
- Guillian Barre syndrome is a progressive demyelinating autoimmune disorder triggered by an acute bacterial or viral infection.
- Presents with:
- rapid onset weakness and tingling that spread through the body
- prickling, pins and needles in peripheries
- Weakness in legs that spreads up body, unsteady walking
- difficulty with eye/ facial movements
- Generally starts in feet/legs and spreads upwards
- Peak symptoms 2-4 weeks after onset
- Can lead to paralysis
- Three forms:
- AIDP - acute inflammatory demyelinating polyradiculoneuropathy - most common
- miller fisher syndrome - ocular form
- Acute motor axonal neuropathy –> aggressive and nondemyelinating
- Treatment:
- Immunoglobulins
- Plasmapheresis (like dialysis but removes harmful antibodies).
- Good prognosis
What is multiple sclerosis?
How does it normally present?
How is MS diagnosed?
- Multiple sclerosis is a primary inflammatory, autoimmune disease causing CNS demyelination.
- Presents with neuropathy —> usually 1 feature initially , either blindness, weakness or numbness
Often presents with optic neuritis, may present similar to stroke.
- MS normally diagnosed via symptoms, there has to multiple systems of the CNS involved in the symptoms.
If there is only 1 symptom could infer it is only a lacunar infarct, if there are multiple areas affected (visual/ weakness/ numbness) likely to be MS.
Also take CSF sample —> looking for oligoclonal bands (immunoglobulins against oligodendrocytes). However not all MS patients will present with this —> 70%.
How can Multiple Sclerosis present differently?
- There are multiple types of MS (8 forms). The relapsing/ remitting course is the most likely.
- The benign form presents with its initial symptoms for a certain but then returns back to their normal function.
- Relapsing/ remitting—> patients start at a baseline level of disability and may have an episode/ attack in which symptoms worsen. They then return to this new baseline level of disability inbetween, worsening at next attack.
- Progressive forms:
- Secondary progressive —> No new disability in between attacks but then followed by a steady increase in disability.
- Primary progressive —> steady increase in disability without attacks.
How might MS present on a CT/MRI?
Outline the gross pathological changes of MS?
- Presents as loss of deep white matter
- Plaques which are the product of inflammation accumulate in demyelinated areas, seen as flares in white matter regions of the CNS.