Movement disorders

Question 1

What is the function of the direct motor pathway?

Answer 1

T o intiate movement via inhibition of inhibitory process

Question 2

What is the function of the indirect motor pathway?

Answer 2

Reduce movement or inhibit unwanted movements

Question 3

What is parkinsons disease

Answer 3

Parkinsons is a neurological disorders due to loss of dopaminergic neurones from the substantia nigra pars compacta = resulting in decreased activation of the direct pathway D1 and decreased inhibitionn of the indirect pathway D2

IDIOPATHIC

Question 4

What is parkinsons associated with?

Answer 4

Lewy body dementia
As Nigrostriatal pathway neurons die off we also see the formation of proteins called lewy bodies. These are the main identifier of parkinson’s disease but still unsure of relevant mechanism.

If lewy body dementia present first: Lewy body dementia w/ parkinsonism
If parkinson presents first: Parkinson dementia

Question 5

What are the histological hall mark of PD?

Answer 5

In PD, with loss of nigrostatial dopaminergic neurone you get esinophillic inclusion bodies (Lewy Bodies) made of misfolded alpha synuclein
Spreads in ‘prion like’ fashion (causes misfold of other alpha synucelin.

Question 6

What are the cardinal signs of parkinsons?

Answer 6

Bradykinesia + one of:
Postural instability
Rigidity
Tremor

Insideous onset - Slow / Gradual

Question 7

What are the long term manifestations of Parkinson’s

Answer 7

Motor sx:
Fixed facial expression, foot drag, shuffling gait
Motor fluctuations - periods of well/off
Freezing: sudden stop in movements
Dyskinesia - excess involuntary use due to L-dopa

Non motor: Insomnia, sleep disturbance , Psychiatric sx (depression, anxiety, dementia)
Autonomic disturbances: Constipation, urinary frequency (incontinence is rare)

Question 8

What are the histological hall mark of PD?

Answer 8

In PD, with loss of nigrostatial dopaminergic neurone you get esinophillic inclusion bodies (Lewy Bodies) made of misfolded alpha synuclein
Spreads in ‘prion like’ fashion (causes misfold of other alpha synucelin.

Question 9

How is PD diagnosed?

Answer 9

Clinical - cardinal features: Bradykinesia + 1 of tremor, rigidty, postural instability

other investigation to consider
MRI - rule out other causes
SPECT w/ DAT SCAN Single photon emission CT with DAT scan - Dopamine Transporter Scan radiotracer to see dopamine uptake in neurones (differentiates between essential tremor and PD

Question 10

Principle of Parkinsons treatment

Answer 10

To reduced effects of loss of dopaminergic neurones via potentiating dopamine ativity and decreasing acetylcholine activity

1st line: L-Dopa + Decarboxylase Inhibitor (Co-beneldopa)
2nd line : MAO-B Inhibitors - (Monamino-oxidase: Selegiline, rasagiline

If young and ASX - Dopamine agonists - Ropinrole

Adjuvant treatments:
COMT Inhibitors - (Catechol-O-methyl transferase)
Deep-brain simulation

Question 11

What is essential tremor?

Answer 11

Progressive tremor affecting predominantly the upper limb

Question 12

Describe some features of an essential tremor?

Answer 12

Absent at rest
Occurs in posture and with movement (i.e. it is an action tremor).
Typically no neurological signs or symptoms
Aetiology unknown ~ but some form of inheritance

Question 13

How may an essential tremor present

Answer 13

Question 14

What are the diagnostic criteria for essential tremor

Answer 14

Tremor>3yrs with no neurological deficit

Question 15

DX Essential tremor

Answer 15

No test - done clinically
Exclude other causes such as:

Hyperthyroidism
Wilsons disease
liver failure
PD
medication: lithium, alcohol withdrawal

Question 16

How to differntiate between PD and essential tremor?

Answer 16

PD has neurological deficit + Pill rolling hand tremor

Question 17

How to manage an essential tremor

Answer 17

1st line - Propanolol
2nd line Primidone (AED)

if sever - gabapentin/benzodiazapines

Deep brain simulation

Question 18

What is Huntington’s Disease

Answer 18

Huntington’s disease (HD) is an autosomal-dominante inherited, neurodegenerative condition

Characterised by:
chorea, dystonia and cognitive changes.

Chorea. Chorea is characterized by repetitive, brief, irregular, somewhat rapid, involuntary movements. The movements typically involve the face, mouth, trunk and limbs. Chorea can look like exaggerated fidgeting.
Dystonia. This condition involves sustained involuntary muscle contractions with twisting, repetitive movements. Dystonia may affect the entire body or one part of the body.

Question 19

What kind of mutation is present in huntington disease?

Answer 19

Autosomal dominant inheritance
Trinucleotide expansion
CAG repeats on HTT on chromosome 4
The more repeats = More severe, earlier onset
<28 CAG repeats = No Huntington / increased %
36-39 CAG repeats ~ variable penetrance
>40 CAG repeats ~

Question 20

How would huntingtons present?

Answer 20

Chorea - Hyperkinesia -
Excessive involuntary limb jerking
Late: Dysphagia, speech difficulties, more parkinsonian features such as rigidty and bradykinesia

Psych features: Mood change, depression, paranoia, irrtiability, agigtation

Coignitive impairments: Progressive memory loss and dementia

Question 21

How is huntingtons chorea diagnosed?

Answer 21

1. FHX
2. CAG testing - BLOOD PCR + electrophoresis
3. Clincal signs of huntingtons: Motor chorea, physc, cognitive impairment

Question 22

How is huntingtons treated?

Answer 22

Counselling
Non pharma: occupational therapy, physiotherapy, speech and language therapy, and nutritional support, exercise

Control cormorbidities:

Chorea: Benzodiazapine
Depression: SSRI- citalopram
Psych features: Anti-psychotics Holoperidol