Dementia & Degeneration Flashcards
Which diseases are characterised by central degeneration?
- Alzheimer’s - Multiple Sclerosis - Parkinson’s - Huntington’s
Which diseases are characterised by peripheral degeneration?
-Diabetic Neuropathy -Motorneuron disease -ALS -Guillain Barre Sydrome
Name 3 types of neurodegeneration
-Wallerian -Axonal -Myelin
Describe Wallerian degeneration
- Distal degeneration of axon and myelin, generally trauma induced. -Rupture - cuts transmission completely
Describe Axonal degeneration
-Dying back of the axon proximal to cell body -Some regeneration is possible -progressive
Describe myelin degeneration
-Loss of oligodendroglial (central)/Schwann (peripheral) cells affecting conduction velocity -Seen in MS (central) -Seen in Guillain Barre (peripheral)
Name 2 causes of Wallerian Degeneration
-Head trauma (shaken baby syndrome, diffuse axonal injury) -Nerve compression
Why is regeneration more likely in the periphery rather than central nervous system?
-Schwann cells in the periphery are better than oligodendroglial cells at releasing growth factors
What are the 3 classifications of Wallerian degeneration?
- Neuropraxia 2. Axonotmesis 3. Neurotmesis
What are amyloid plaques?
-Aggregations of misfolded/fragmented proteins -Caused by changes in phosphorylation or protein folding -Lead to increased Beta sheet formation
What are beta-amyloid plaques associated with?
Alzheimers disease
what are alpha-synuclein associated with
Parkinson’s disease
What are prion proteins associated with?
CJD
What are Tau proteins?
Maintain the structural composition of microtubules, allowing transport through the neuron.
What are neurofibrillary Tangles?
- Hyperphosphorylation of tau proteins leads to misfolding -misfolding causes breakdown of tubules, B-sheet and fibril formation -Fibrils aggregate to form tangles. -This occurs OUTSIDE the cell
What are inclusions?
-Intracellular protein aggregations including LEWY BODIES and PICK CELLS -Generally alpha-synuclein -Inclusions are INTRACELLULAR
How does diabetic neuropathy present and what is it caused by?
Presentation: Pain, ulcers, tingling, poor balance Caused by: microvascular disease, activated PKC, polyols (secondary to high glucose)
How does Motor Neuron Disease (MND) present?
- UMN and LMN features -Bulbar or pseudobulbar features -muscle weakness and atrophy -no sensory signs, bladder involvement or ocular involvement
What is MND caused by?
-Degeneration of the motor pathways, affecting outflow from the anterior horn cells
What is Guillain-Barre Syndrome?
- Autoimmune reaction triggered by preceding viral/bacterial infection -Rapid onset weakness and tingling that spreads through the body. Normally starts in the feet/legs and spreads upwards -Demyelinating disorder -Treated with IV immunoglobulins and plasmapheresis
What is Multiple Sclerosis?
-Primary inflammatory, autoimmune disease causing CNS demyelination (oligodendroglial cells)
How does multiple sclerosis present?
-Neuropathy -Blindness -Weakness -Numbness Diagnosis is based on demonstration of multiple levels of CNS involvement and CSF sample immunoglobulin bands. MRI: Plaques of products of inflammation accumulate in demyelinated areas, seen as flares in white matter regions of CNS on
What are the different types of MS?
-Benign = No disability, return to normal between attacks, least impact on quality of life - Relapsing-Remitting = Episode + slight deterioration which becomes new baseline = most common - Secondary Progressive = no new disability between attacks, followed by steady increase in disability - Primary progressive = Steady increase in disability without attacks - worst case and the fastest decline
What would be seen in Histology for a patient with Parkinson’s Disease?
-Loss of Dopamine neurons in substantia nigra -Presence of Lewy Bodies -Raised alpha-synuclein/parkin levels -Also get inclusions