Degeneration and Dementia Flashcards
What are the three types of damage that you see in the peripheral nervous system?
- Neuropraxia; least severe, with no damage to axons or sheathing, often the result of stretching or compression
- Axontomesis; moderate, axons damaged but sheathing intact
- Neurotmesis; most severe, partial or complete severance of axon and sheathing, likelihood of recovery dependent on type of cut
What is Wallerian degeneration?
Degeneration of the distal portions of the axon and myelin
What is axonal degeneration?
Dying back of the neuron
What is demyelination?
Loss of oligodendral or schwann cells
Why is regeneration of damaged axons more likely in the peripheral nervous system?
Schwann cells play a role in maintaining the optimal environment to enable regrowth whereas oligodendroglial cells do not contribute to the maintenance of local environment as significantly in the CNS
What is transneuronal degeneration?
The death of cells within the communication chain as they are no longer in use
What are the main structures looked for when assessing for neurodegenerative disorders?
- Amyloid plaques
- Neurofibrillary tangles
- Inclusions
- Prion proteins
How are plaques caused in the brain?
Plaques are caused by changes in protein phosphorylation, which leads to changes in protein folding and the formation of β-sheets. These sheet form insoluble fibres and toxic oligomers, which can clump together to form plaques
What are the different types of amyloid plaques? and in which disease are they found most frequently
- β-amyloid (fragments of the amyloid precursor protein) in Alzheimer’s Disease
- α-synuclein (which mostly form fibrils) in Parkinson’s Disease
- Prion proteins in Creutzfeld Jakob Disease (CJD)
What microtubule associated protein most commonly forms neurofibrillary tangles?
Tau
How do neurofibrillary tangles form?
Hyperphosphorylation of tau leads to misfolding, which then causes the breakdown of the microtubules, β-sheet and fibril formation. These fibrils aggregate to form tangles.
What are inclusions?
Inclusions are intracellular protein aggregations (compared to plaques, which are found in the extracellular matrix), and include:
- Lewy bodies
- Pick cells
What proteins form inclusions?
Inclusions are generally made from α-synuclein but may be formed by other proteins including:
- ubiquitin
- crystallin
- neurofilament
Give some examples of peripheral degenerative disorders
- Diabetic Neuropathy
- Motorneuron disease (MND)
- Amylotrophic Lateral Sclerosis aka Lou Gehrig’s Disease
- Friedrich’s ataxia
- Guillain Barre Syndrome (GBS)
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Give some examples of central degenerative disorders
- Multiple Sclerosis
- Parkinson’s
- Huntington’s
- Spongiform encephalopathies
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How would you describe the form of the neuropathy in diabetic neuropathy?
Axonal (dying back)
How does diabetic neuropathy present?
Commonly presents with pain and ulceration as a result of poor circulation. If pain absent the patient may feel tingling and experience poor balance.
What causes the degeneration in diabetic neuropathy?
- Microvascular disease
- Glycolated end products, activated PKC, Polyols (secondary to high glucose)
List the ways MND is grouped according to the level of involvement
- Motor Cortex
- Corticobulbar Pathways (pseudobulbar palsy)
- Cranial Nerve Nuclei (progressive bulbar palsy)
- Corticospinal Tract (primary lateral sclerosis)
- Anterior Horn Cell (progressive muscular atrophy)
What is the known cause of Amylotrophic lateral sclerosis?
Changes in the SOD1 gene leads to protein misfolding, reduced ROS (Reactive oxygen species) removal and increased cell damage and death.
Where does the loss of motor neurons commonly occur in amylotrophic lateral sclerosis?
In ALS, the loss of motor neurons occurs predominantly at the level of the corticospinal tract (the large Betz cells) and anterior horn cells, leading to thinning of anterior roots and fibre pathways.
How is amylotrophic lateral sclerosis characterised post-mortem and histologically?
- Gliosis (hypertrophy of glial cells) - Astrocytosis
- Lateral column degeneration
- Muscle atrophy
What causes Freidrich’s ataxia?
Friedrich’s ataxia is an autosomal recessive disorder, caused by GAA triplet repeats in FXN gene (Frataxin), which leads to problems with iron metabolism.
What tracts are damaged in Freidrich’s ataxia?
In the motor system there is a loss of large myelinated fibres in the spinocerebellar tracts, dorsal root ganglia and posterior column. Later loss includes cerebellar mass and corticospinal tracts.
What are the key pathological manifestations of Freidrich’s ataxia?
Key features are cerebellar:
- Progressive limb and gait ataxia
- Dysmetria
- Dysarthria
- Poor balance (sensory ataxia)
- Loss of joint position and vibration senses
- Absent tendon reflexes in lower limb (extensor plantar)
- Muscle weakness
What is the suspected cause of Guillain-Barre syndrome?
It is suspected to be an autoimmune reaction, triggered by preceding viral/bacterial infection.
What will patients with GBS experience?
Patients with GBS experience rapid onset weakness and tingling that spreads through body. This normally starts in feet/legs and spreads upwards. Peak symptoms occur approx. 2-4 weeks after onset and it can lead to paralysis.
