Week 2 Neurology Dementia And Tremor

Question 1

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?

Answer 1

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

Question 2

What are the two main components of Alzheimer’s pathophysiology

Answer 2

Amaloid plaques (A-beta)

Tau tangles

Question 3

Regarding memory, learning and emotion which part of the brain does Alzheimer’s effect?

Answer 3

The hippocampus

Question 4

Main Alzheimer’s treatment

Answer 4

Cholinesterase inhibitors prevent the breakdown of ACh. There is a shortage of ACh in Alzheimer’s patients particularly in the hippocampus

Question 5

What are the risk factors for vascular dementia?

Answer 5

Same of for CV disease and stroke

Question 6

How does the progression of vascular dementia differ to that of Alzheimer’s

Answer 6

Vascular gets worse in steps each time there is a vascular event e.g. tia

Question 7

What is the focus of vascular dementia treatment?

Answer 7

Question 8

Main differences between Alzheimer’s and frontotemporal dementia?

Answer 8

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

Question 9

What is lewy-body dementia

Answer 9

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

Question 10

How do MRIs of the hippocampus and dopamine scans of the basal ganglia vary between between those suffering from Alzheimer’s and LBD

Answer 10

Question 11

Fill in the blanks

Answer 11

Question 12

What are the four symptoms collectively known as parkinsonism?

Answer 12

• Bradykinesia - slow movement
• Rigidity
• Tremor
• Postural instability

Question 13

What are 6 non motor symptom of Parkinson’s disease?

Answer 13

• Cognitive impairment
• Depression
• Anxiety
• REM sleep behaviour disorder
• Constipation
• Pain

Question 14

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?

Answer 14

• SNCA(encoding alpha-synuclein)
• Parkin
• PINK1
• DJ-1
• LRRK2

LRRK2 is responsible for late onset parkinson’s

Question 15

Average age of onset of Parkinson’s?

Answer 15

60

Question 16

Is Alzheimer’s genetic?

Answer 16

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)

Question 17

Where do Lewy bodies begin in Parkinson’s?

Answer 17

Lewy body progression
Lewy bodies first appear in the medulla & olfactory bulb and then progressively spread to the pons, midbrain, limbic lobe and neocortex

Question 18

What happen’s at stage 6?

Answer 18

You get all the symptoms of Lewy Body dementia

Question 19

Lack of which neurotransmiter is responsible for parkinsonism?

Answer 19

Dopamine

Question 20

Build of Lewy Bodies in which part of the brain is specifically causes parkinsonism?

Answer 20

Substantia Nigra

Question 21

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

Answer 21

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

Question 22

When it comes to the motor cortex -> basal ganglia -> thalamus axis what does the direct pathway promote?

Answer 22

Movement

Hint -> to move somewhere take the most direct route

Question 23

Breif overview of parkinson’s medication (all focus on dopamine)

Answer 23

Question 24

What is the suffix for dopamine precursers?

Answer 24

“Dopa”

Levadopa
Carbidopa

Question 25

What is the suffix for MAO-B inhibitors? What do they do?

Answer 25

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

Question 26

What do COMT inhibitors do? What is the suffix?

Answer 26

Block breakdown of dopamine precursors like levadopa "Capone" Al capone like comte cheese

Question 27

Fill in this table on the types of tremor

Answer 27

Question 28

What is the main cause of physiological tremor?

Answer 28

Often due to over-activity of sympathetic nervous system ‘fight or flight’ Often postural/action Occurs with anxiety, caffeine, β-2-agonists, hyperthyroidism

Question 29

Common characteristics of essential tremor?

Answer 29

Autosomal in 50 % of cases Often an action tremor Relieved with alcohol

Question 30

Common features of Parkinson's tremor?

Answer 30

Slow and corse "Pill rolling" Most prominant at rest but present during walking

Question 31

What is intention tremor and what is it a sign of?

Answer 31

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

Question 32

Terms for amplitude of tremor

Answer 32

Fine: low amplitude Corse: large amplitude

Question 33

In MND what is the typical features of a degenerating cell?

Answer 33

A degenerating cell containing eosinophilic 'Bunina bodies' which are typical of classical MND. Ends up with aggregates of missformed TDP-43 protein (brown) 

Question 34

Motor cortex features in MND?

Answer 34

Motor cortex atrophy

Question 35

What is the protein found missformed and which then aggregates in MND?

Answer 35

TDP-43 Hint: At 43 Teedee Peeded (due to MND)

Question 36

What spinal chord features do you get in MND?

Answer 36

Thinning of atrophic anterior roots (arrows).

Question 37

What is an anterior horn cell?

Answer 37

Anterior horn cells are large motor neurons in the spinal cord that trigger muscle responses

Question 38

What is this?

Answer 38

C is a normal anterior horn cell D is a degenerated one with a bunina body (arrow)

Question 39

What is the difference between ALS and MND?

Answer 39

ALS is a subtype on MND and is the most common occuring in 60-70% of MND cases

Question 40

What does ALS stand for?

Answer 40

Amyotrophic lateral sclerosis Myo - muscle A-Trophic - without nourishment (no nerve orders) Lateral - because you see atrophy of the spinal roots?

Question 41

What is ALS also known as?

Answer 41

Spinal onset MND

Question 42

What is the second most common form of MND?

Answer 42

Progressive bulbar palsy 10-20% This just affects speech and swallowing

Question 43

Third most common form of MND?

Answer 43

Progressive muscular atrophy 10% This only effects the LMN

Question 44

What form of dementia has an overlap with MND?

Answer 44

Frontotemporal dementia (this covers whent he motor neurons are)

Question 45

What is tounge atrophy a common feature of?

Answer 45

MND

Question 46

Two biggest genes involved in autosomal MND?

Answer 46

1: C9orf72 2: SOD1 Hint: I wanted to go to Corfu but sod's law I got MND

Question 47

First line of treatment for essential tremor?

Answer 47

Propanolol

Question 48

What type of scan might you need to diagnose parkinsons?

Answer 48

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

Question 49

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

Answer 49

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.