Neurodegeneration

Question 1

What is alzheimer’s disease?

Answer 1

• cortical atrophy and loss of neurones
• frontal and temporal lobes
• unknown aetiology but know risk factors

Question 2

Huntington’s chorea

Answer 2

• genetic
• basal ganglia and parts of cerebral cortex
• striatum neuronal cell death and parietal and frontal cortex death
• decrease in ACh and GABA

Question 3

What is the epidemiology of Alzheimer’s disease?

Answer 3

• accounts for 50-70% of all dementias
• most common form of dementia
• male = female
• 90% > 60yrs

Question 4

What are the risk factors for Alzheimer’s disease?

Answer 4

• advancing age
• family Hx: mostly for early onset presentation
• APOE genotype
• obesity, insulin resistance
• vascular factors, dyslipidaemia, hypertension
• inflammatory markers
• down syndrome
• traumatic injury

Question 5

What is the pathology of Alzheimer’s disease?

Answer 5

• 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

Question 6

What are the clinical features of Alzheimer’s disease?

Answer 6

• 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

Question 7

What is ALS?

Answer 7

• Amyotrophic lateral sclerosis
• rare progressive condition characterized by degeneration of UMN and LMN
• has many forms
• atrophy, fasciculations, weakness, hypertonia, hypereflexia

Question 8

What is the pathology of ALS?

Answer 8

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

Question 9

What does ALS in frontal lobe cause?

Answer 9

dementia

Question 10

What does ALS in corticobulbar tract and nuclei cause?

Answer 10

pseudo bulbar palsy

Question 11

What does ALS in cranial nerve nuclei cause?

Answer 11

progressive bulbar palsy

Question 12

What does ALS in lateral column cause?

Answer 12

primary lateral sclerosis

Question 13

What are the clinical features of amyotrophic lateral sclerosis?

Answer 13

• 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

Question 14

What is Parkinson’s disease?

Answer 14

• chronic degeneration of basal ganglia

* Bradykinesia, rigidity, tremor, postural instability

Question 15

What is the epidemiology of Parkinson’s disease?

Answer 15

• most common basal ganglia disease
• incidence 20/100 000
• F:M 2:3
• > 50s

Question 16

What is the aetiology of Parkinson’s disease?

Answer 16

• 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

Question 17

What is the pathology of Parkinson’s disease?

Answer 17

• 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

Question 18

What are the clinical features of Parkinson’s disease?

Answer 18

• 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

Question 19

Festination

Answer 19

Parkinson’s patient:

-steps suddenly quicken and patient may run to keep from falling

Question 20

How does a decrease in dopamine in Parkinson’s lead to the symptoms?

Answer 20

• 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

Question 21

What happens in the pathways in Huntington’s disease?

Answer 21

• 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

Question 22

What is motor neurone disease?

Answer 22

Group of diseases in which UMNs and LMNs undergo progressive degeneration and die

Question 23

List the motor neurone diseases?

Answer 23

• Amyotrophic Lateral Sclerosis (ALS)
• Progressive Muscular Atrophy (PMA)
• Progressive Bulbar Palsy (PBP)
• Primary Lateral Sclerosis (PLS)

Question 24

What is the pathophysiology in Huntington’s disease?

Answer 24

• 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

Question 25

Discuss the use of genetic testing in Huntington’s disease

Answer 25

• 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..