Neurodegeneration Flashcards
What is alzheimer’s disease?
- cortical atrophy and loss of neurones
- frontal and temporal lobes
- unknown aetiology but know risk factors
Huntington’s chorea
- genetic
- basal ganglia and parts of cerebral cortex
- striatum neuronal cell death and parietal and frontal cortex death
- decrease in ACh and GABA
What is the epidemiology of Alzheimer’s disease?
- accounts for 50-70% of all dementias
- most common form of dementia
- male = female
- 90% > 60yrs
What are the risk factors for Alzheimer’s disease?
- advancing age
- family Hx: mostly for early onset presentation
- APOE genotype
- obesity, insulin resistance
- vascular factors, dyslipidaemia, hypertension
- inflammatory markers
- down syndrome
- traumatic injury
What is the pathology of Alzheimer’s disease?
- continuum of changes btw aging brain and AD
- loss of neurones and synapses
- atrophy of cerebral cortex
- neurofibrillary tangles and senile plaques in the cerebral cortex and hippocampus
What are the clinical features of Alzheimer’s disease?
- insidious onset
- short term memory loss first, then long-term
- confusion, disorientation
- higher order functions reduced (problem solving, judgement, abstract thinking)
- behavioural changes (irritability, restlessness), mood changes
- motor changes
- faster progression if early onset
What is ALS?
- Amyotrophic lateral sclerosis
- rare progressive condition characterized by degeneration of UMN and LMN
- has many forms
- atrophy, fasciculations, weakness, hypertonia, hypereflexia
What is the pathology of ALS?
Thinning of anterior roots of spinal cord (most in cervical and lumbosacral regions)
Can affect: • motor cortex • frontal lobe • corticobulbar tract and nuclei • cranial nerve nuclei • lateral column • anterior horn cells • U and LMN
What does ALS in frontal lobe cause?
dementia
What does ALS in corticobulbar tract and nuclei cause?
pseudo bulbar palsy
What does ALS in cranial nerve nuclei cause?
progressive bulbar palsy
What does ALS in lateral column cause?
primary lateral sclerosis
What are the clinical features of amyotrophic lateral sclerosis?
- weakness (#1)
- unilateral first
- later, muscle wasting (thenar eminence #1)
- fasciculations, spasticity
- unremitting
- difficulty talking and swallowing
Later:
• bowel and bladder function loss
• Babinski and clonus sign
NO:
• cerebellar signs
• basal ganglia signs
• intellectual change
What is Parkinson’s disease?
- chronic degeneration of basal ganglia
* Bradykinesia, rigidity, tremor, postural instability
What is the epidemiology of Parkinson’s disease?
- most common basal ganglia disease
- incidence 20/100 000
- F:M 2:3
- > 50s
What is the aetiology of Parkinson’s disease?
- idiopathic
- 5% are genetic
Maybe secondary to:
• drug use
• head and peripheral trauma
Other causes: • post-encephalitis • carbon monoxide, manganese poisoning • hydrocephalus • tumours • degenerative disorders
What is the pathology of Parkinson’s disease?
- damage to neurones in substantia nigra (and areas that make dopamine)
- decrease in dopamine in nigrostriatal pathway (substantia migra and corpus striatum)
- not enough dopamine -> not enough inhibition of striatum -> too much ACh and GABA from striatum
What are the clinical features of Parkinson’s disease?
- insidious onset of slow movement, weakness, tremor
- tremor: at rest, gone with movement, more with stress
- pill rolling tremor
- handwriting small and scratchy, hard to do fine movement tasks
- muscle ache, fatigue, mask face, few blinks
- stooped posture, difficulty walking, shuffling short steps, no arm swing, poor balance
- festination
- increased salivaiton
- increased muscle tone, difficult PROM
- dementia later
Festination
Parkinson’s patient:
-steps suddenly quicken and patient may run to keep from falling
How does a decrease in dopamine in Parkinson’s lead to the symptoms?
- dopamine increases Direct pathway and decreases Indirect pathway
- Direct pathway = more motor output
- Indirect pathway = motor inhibition
So in Parkinson’s there is low dopamine:
- less direct = less motor output
- more indirect = less motor output
What happens in the pathways in Huntington’s disease?
- indirect pathway first
- not enough ACh or GABA (usually they stimulate indirect path)
- not enough indirect path = too much movement
• late stage: affects indirect pathway -> hypokinesia -> akinesia
What is motor neurone disease?
Group of diseases in which UMNs and LMNs undergo progressive degeneration and die
List the motor neurone diseases?
- Amyotrophic Lateral Sclerosis (ALS)
- Progressive Muscular Atrophy (PMA)
- Progressive Bulbar Palsy (PBP)
- Primary Lateral Sclerosis (PLS)
What is the pathophysiology in Huntington’s disease?
- gene codes for production of a protein called “huntingtin” -> invades cell and kills it
- disease of basal ganglia and parts of cerebral cortex
- death of neurone cells in: striatum, parietal and frontal cortex
- decrease in ACh and GABA
Discuss the use of genetic testing in Huntington’s disease
- inherited disease (single abnormal gene)
- people carry the abnormal gene that will cause them to develop the disease
- no cure for this fatal disease
- deciding to be tested can be difficult
- does knowing you have an expiration date affect how you live?
- symptoms start when you already have kids..