Degeneration and Dementia Flashcards
What are the different types of neurodegeneration?
Wallerian – distal degeneration of axon and myelin
Axonal – dying back of axon proximal to cell body
Myelin – loss of oligodenrdroglial/schwann cells affecting conduction velocity
Multiple Sclerosis (central)
Guillain Barré (peripheral)
What are the common causes of wallerian degeneration and what are its 3 classifications?
Head trauma (DIA/ SBS) / nerve compression
Neuropraxia
Axonotmesis
Neurotmesis
What protein related changes would you see in neurodegenerative disorders?
Amyloid plaques
Tau (Neurofibrillary tangles)
Lewy Bodies/Pick cells ((inclusions)
Prion proteins
What amyloid plaques are found in Parkinsons and Mad cow disease?
PD - alpha-synuclein
CJD - Prion
What are inclusions?
Intracellular protein aggregaations - lewy bodies/pick cells alpha-synuclein ubiquitin crystallin neurofilament
What are prion proteins?
proteinaceous infectious particle
presynaptic transport and cell signalling
β–sheets and fibrils
Visible amyloid plaques and vacuolisation giving spongiform appearance
What are examples of peripheral and central degenerative disorders?
Peripheral: Diabetic Neuropathy Motorneuron disease (MND) Amylotrophic Lateral Sclerosis Guillain Barré syndrome Central: Multiple Sclerosis Alzheimer’s Parkinson’s Huntington’s
What causes motor neuron disease?
degeneration of the motor pathways, affecting outflow from the anterior horn cells
What causes amylotrophic lateral sclerosis?
Changes in SOD1 gene lead to protein misfolding, reduced ROS (reactive oxygen species) removal
Loss of motor neurons - at the level of the corticospinal tract (Betz cells) and anterior horn cell. Thinning of anterior roots and fibre pathways.
What causes Guillain-Barré syndrome?
Cause unknown, autoimmune reaction triggered by preceding viral/bacterial infection
What are the symptoms of Guillain-Barré syndrome?
Rapid onset weakness and tingling that spreads through body
Normally starts in feet/legs and spreads upwards
Peak symptoms occur approx. 2-4 weeks after onset
Can lead to paralysis
What is multiple sclerosis? what causes it? what are the symptoms?
Primary inflammatory, autoimmune disease causing CNS demyelination
Diff patterns of disease - relapsing remitting most likely
Optic neuritis
weakness
numbness
In a CSF sample, if you found oligoclonal (immunoglobin) bands, what does that indicate?
Multiple Sclerosis
What pathological proteins are found in parkinsons? and where?
Alpha Synuclein - substantia nigra par compacta
What are the symptoms of parkinsons? (TRAP)
Tremors
Rigidity
Akinesia
Postural instability
How can you truly diagnose parkinsons?
Post-mortem biopsy:
Loss of DA neurons in SN
Presence of Lewy Bodies
Raised α-synuclein/parkin levels
What are the causes of huntingtons disease?
Genetic – autosomal dominant Loss of GABA neurons Loss of cholinergic function (Ach) Astrocytosis (inc) Loss of Substance P
In imaging, if you see a Shrunken caudate head and Ex vacuo dilatation, what can you diagnose?
Huntingtons
What are the causes of Spongiform encephalopathies/
Creutzfeld-Jakob disease?
Prion protein alteration from PrPc to PrPsc
Genetic
Transmissable
What are examples of acute, subacute and chronic diseases?
Acute (weeks) - encephalitis
Subacute (months) - CJD
Chronic (years) - Alz, normal pressure hydrocephalus
What is the gross morphology of Alzheimer’s? That you can confirm with.
Cerebral atrophy - hippocampal/temporal/cortical
What is the most common type of dementia?
1st - AD
2nd - Vascular dementia (stroke related)
3rd - Dementia with lewy bodies (DLB)
4th - Fronto-temporal dementia
What are the protein deposits in DLB?
alpha-synuclein
Dopamine and Acetycholine neurons lost
How can you image a DLB?
DaTSCAN - may show reduced striatal DAT binding in DLB patients
What are the 3 cardinal features of normal pressure hydrocephalus? How can it be detected on imaging?
Gait disturbance
Cognitive decline – subcortical pattern
Urinary incontinence
Characterised by ventriculomegaly on imaging
