Week 2 Neurology Dementia And Tremor Flashcards
An 82-year-old man is being investigated for a cognitive impairment and concerns about a movement disorder. As part of the assessment he is referred for a number of scans.
The results are as follows:
MRI head normal age-related changes
SPECT scan reduced dopaminergic activity in the substantia nigra
Given the above information, what is the likely diagnosis?
Parkinson’s disease
Parkinson’s Disease is a neurodegenerative disorder involving death of neurones in the substantia nigra. The substantia nigra contains dopaminergic cells
There is no noticeable atrophy on a CT such as with Alzheimer’s
What are the two main components of Alzheimer’s pathophysiology
Amaloid plaques (A-beta)
Tau tangles
Regarding memory, learning and emotion which part of the brain does Alzheimer’s effect?
The hippocampus
Main Alzheimer’s treatment
Cholinesterase inhibitors prevent the breakdown of ACh. There is a shortage of ACh in Alzheimer’s patients particularly in the hippocampus
What are the risk factors for vascular dementia?
Same of for CV disease and stroke
How does the progression of vascular dementia differ to that of Alzheimer’s
Vascular gets worse in steps each time there is a vascular event e.g. tia
What is the focus of vascular dementia treatment?
Main differences between Alzheimer’s and frontotemporal dementia?
AD primarily affects the medial temporal and parietal lobes, especially the hippocampus, which is involved in memory and learning
FTD primarily affects the lateral frontal and temporal lobes, areas involved in behavior, personality, and language
Both have a build up of Tau, only Alzheimer’s has the amaloid plaques.
Age of onset is younger is frontotemporal dementia 45-65
What is lewy-body dementia
Pathophysiology is a build up of alpha-synuclein
Affects temporal, midbrain and parietal
Motor symptoms of Parkinson’s but with added dementia symptoms including sleep disorders
How do MRIs of the hippocampus and dopamine scans of the basal ganglia vary between between those suffering from Alzheimer’s and LBD
Fill in the blanks
What are the four symptoms collectively known as parkinsonism?
- Bradykinesia - slow movement
- Rigidity
- Tremor
- Postural instability
What are 6 non motor symptom of Parkinson’s disease?
- Cognitive impairment
- Depression
- Anxiety
- REM sleep behaviour disorder
- Constipation
- Pain
Which of these genes have links to parkinson’s?
- PTCH1
- SNCA(encoding alpha-synuclein)
- Parkin
- APC
- PINK1
- Amyloid precursor protein (APP)
- SUFU
- DJ-1
- LRRK2
- Presenilin 1 (PSEN1)
- Presenilin 2 (PSEN2)
Bonus: which is responsible for late onset parkinsons?
- SNCA(encoding alpha-synuclein)
- Parkin
- PINK1
- DJ-1
- LRRK2
LRRK2 is responsible for late onset parkinson’s
Average age of onset of Parkinson’s?
60
Is Alzheimer’s genetic?
Mostly no.
However half of early onset Alzheimer’s is caused by these three genes:
- Amyloid precursor protein (APP):
- Presenilin 1 (PSEN1)
- Presenilin 2 (PSEN2)
Where do Lewy bodies begin in Parkinson’s?
Lewy body progression
Lewy bodies first appear in the medulla & olfactory bulb and then progressively spread to the pons, midbrain, limbic lobe and neocortex
What happen’s at stage 6?
You get all the symptoms of Lewy Body dementia
Lack of which neurotransmiter is responsible for parkinsonism?
Dopamine
Build of Lewy Bodies in which part of the brain is specifically causes parkinsonism?
Substantia Nigra
How does dopamine from the substantia nigra involved in the direct and indirect pathways?
And how does a lack of dopamine cause parkinsonism?
Draw out pathways
Dopamine form the substantia nigra favours the direct pathway which promotes movement
When dopamine is diminished indirect pathway is favoured causing the bradykinisia and stiffness. The tremor comes because there isn’t enough dopamine to decide which one to take resulting in both and tremor
When it comes to the motor cortex -> basal ganglia -> thalamus axis what does the direct pathway promote?
Movement
Hint -> to move somewhere take the most direct route
Breif overview of parkinson’s medication (all focus on dopamine)
What is the suffix for dopamine precursers?
“Dopa”
Levadopa
Carbidopa
What is the suffix for MAO-B inhibitors?
What do they do?
Line
“Gis us a line” MAO-B inhibitors cause drugs to work wayyyyy better
Inhibit the enzyme monoamine oxidase B which breaks down dopamine
e.g.
Rasagiline
Selegiline
What do COMT inhibitors do?
What is the suffix?
Block breakdown of dopamine precursors like levadopa
“Capone”
Al capone like comte cheese
Fill in this table on the types of tremor
What is the main cause of physiological tremor?
Often due to over-activity of sympathetic nervous system ‘fight or flight’
Often postural/action
Occurs with anxiety, caffeine, β-2-agonists, hyperthyroidism
Common characteristics of essential tremor?
Autosomal in 50 % of cases
Often an action tremor
Relieved with alcohol
Common features of Parkinson’s tremor?
Slow and corse
“Pill rolling”
Most prominant at rest but present during walking
What is intention tremor and what is it a sign of?
Often a sign of cerebella disease
Ask to point nose to finger, if intention tremor present amplitude will increase (become corse) as it approaches the target.
Can also miss target completely
Terms for amplitude of tremor
Fine: low amplitude
Corse: large amplitude
In MND what is the typical features of a degenerating cell?
A degenerating cell containing eosinophilic ‘Bunina bodies’ which are typical of classical MND.
Ends up with aggregates of missformed TDP-43 protein (brown)
Motor cortex features in MND?
Motor cortex atrophy
What is the protein found missformed and which then aggregates in MND?
TDP-43
Hint: At 43 Teedee Peeded (due to MND)
What spinal chord features do you get in MND?
Thinning of atrophic anterior roots (arrows).
What is an anterior horn cell?
Anterior horn cells are large motor neurons in the spinal cord that trigger muscle responses
What is this?
C is a normal anterior horn cell
D is a degenerated one with a bunina body (arrow)
What is the difference between ALS and MND?
ALS is a subtype on MND and is the most common occuring in 60-70% of MND cases
What does ALS stand for?
Amyotrophic lateral sclerosis
Myo - muscle
A-Trophic - without nourishment (no nerve orders)
Lateral - because you see atrophy of the spinal roots?
What is ALS also known as?
Spinal onset MND
What is the second most common form of MND?
Progressive bulbar palsy 10-20%
This just affects speech and swallowing
Third most common form of MND?
Progressive muscular atrophy 10%
This only effects the LMN
What form of dementia has an overlap with MND?
Frontotemporal dementia
(this covers whent he motor neurons are)
What is tounge atrophy a common feature of?
MND
Two biggest genes involved in autosomal MND?
1: C9orf72
2: SOD1
Hint: I wanted to go to Corfu but sod’s law I got MND
First line of treatment for essential tremor?
Propanolol
What type of scan might you need to diagnose parkinsons?
SPECT (uses radioactive tracer like a PET)
You don;t get niticable signs of atrophy on a CT or MRI like you would with alzheimer’s
A 54-year-old man presents with progressive weakness over the past couple of months. The weakness is mainly affecting his legs which results in him struggling to climb his stairs at home. The weakness is also now affecting his right hand and has led to him dropping objects. On examination, you note thenar muscle atrophy and fasciculations. There is also increased tone in the lower limbs and hyperreflexia of the knee and ankle jerks. No sensory deficit is identified.
What is the most likely diagnosis?
- Primary lateral sclerosis
- Bulbar amyotrophic lateral sclerosis
- Multiple sclerosis
- Spinal amyotrophic lateral sclerosis
- Progressive muscular atrophy
D
Primary lateral sclerosis is usually characterised by purely upper motor neuron features at the onset and may later on progress to lower motor neuron symptoms.
Bulbar ALS is the same as progressive bulbar palsy and is characterised by bulbar symptoms such as slurred speech and difficulty swallowing at the onset and on examination there might also be evidence of fasciulations and muscle wasting of the tongue.
MS would present with a mixture of motor and sensory deficits and only affects upper motor neurons
Patient has presented with symptoms purely affecting his motor function. Examination findings show a mixture of upper motor neuron signs (hyperreflexia and increased tone) and lower motor neuron signs (fasciculations and muscle atrophy). This is highly suggestive of spinal amyotrophic lateral sclerosis (ALS) - the most common variant of motor neuron disease which presents with a mixture of upper and lower motor neuron signs.
This variant of MND only presents with lower motor neuron features and does not correspond with this patient as he has hyperreflexia and increased tone which are upper motor neuron signs.
