Parkinsons and Huntingtons

Question 1

How common is Parkinsons?

Answer 1

Parkinsons is common

Question 2

Huntington’s Chorea

• How it presents
• WHta it is

Answer 2

• Chorea, Tics, Psychiatric symptoms
• Autosomal dominant disease
• CAG repeat of the hUntingtin Gene (chromsome 4p)
• normal number of repeats is 28, diseease occurs at >/40
• ABnormal Huntingtin protein aggregates in cell and is assoicated with cell death
• The more repeats, the earlier and more severe the disease
• Anticipations

Question 3

Diagnosis Huntingtins chorea

Answer 3

• Genetic testing - Genetic counselling prior to diagnostic test, issues around confidentiality
• Differential diagnosis - any other cause of chorea/ tics- always think about Wilson’s disease (autosomal recessive)

Question 4

Treatment Hungtintons

Answer 4

• Maintaining nutrition - associated with improves outcome and need to keep intake as burn lots more with constant movements
• Physiotherapist
• Drug-SYmptomatic treatments: First line VMAT2 inhibitors eg, tetrabenazine (reduce dopamine in presynaptic neuron) or atypical antipsychotic (block dopamine receptors) like lanzopine
• Drugs on horizon - Gene therapy (Deleting excess gene)

Question 6

Normal basal ganglia function - Substnatia nigra

Answer 6

Question 7

Parkinsons disease

Answer 7

Must have bradykinesia and 1 of:

• Rigidity
• Rest tremor (4-6hZ)
• Posutral instability

Question 8

Parkinsons disease pathology - idiopathic

Answer 8

• Misfolding of alpha-synuclein associated with Lewy Bodies and neuronal cell death
• Likely (complex) interplay between genetic and environmental factors
• Neuroinflammation, problems clearing things out of cells (autopahgy), mitochondrial dysfunction etc

Question 9

PD and genetics

Answer 9

• Parents of children with Gaucher’s disease are mor elikely to get PD (GBA homozygous)
• Genetic PD is exception not the rule:
  
  • Autosomal dominant - PARK8 (AKA LRRK2) and SNCA (Park 1/4), mutation in alpha-synuclein (first described but rate)
  • Autosomal recessive - PARK 2 (AKA parkin), problem with clearing toxic proteins.

Question 10

Clinical Diagnosis Parkinson’s disease

Answer 10

UK Brain bank Criteria

ABout diagnosis it, excluding everything else and supportive criteria

Question 11

Premotor features of Parkinsons

Answer 11

• (Loose neurones before get Parkinsons)

Subtle symptoms you can get before getting Parkinsons

• Anosmia
• REM sleep behavior disorder- acting out dreams overnight
• Constipation - changes to nerves in the gut
• (Mood changes)- not that helpful as common in population, same with coxnstipation

Question 12

Non motor symptoms Parkinsons

Answer 12

People really struggle with concentration issues, hallucinations etc

Question 13

The main differential diagnoses Parkinsons

Answer 13

• Essential tremor - refer back to diagnosis parkinsonism on brain bank criteria
• Vascular parkinsonism - repeated strokes and strictly unilateral features after 3y might suggest (on UK brain bank criteria for exlusion criteria).
• Parkinson’s plus syndromes - PSP, MSA, CBS (In pbl) circled below
• Dementia with lewy bodies- some pathological process as PD but the different course of the disease. The onset of cognitive Sx<1year from Parkinsonism or before.

Refer back to the criteria.

Question 14

Essential tremor on DAT scan

Answer 14

This shows in brain, beautiful comma shape

Question 15

Parkinsons disease on DAT scan

Answer 15

Full stops - (comma is Essential trmeor)

Question 16

Levodopa for PD

Answer 16

Need to dopa decarboxylase inhibitor add it to stop dopamine breakign down so can cross BBB to synapse where can go and have downstream effect for lots of Go.

These are the Co-Beneldopa and Co-careldopa

Question 17

Dopamine Agonist for PD

Answer 17

Bind to post synaptic dopamine receptor

Few more side effects but very effective

Can cause impulse contorl disorder with things like gambling

Question 18

Monoamine Oxidase B inhibitors for PD

Answer 18

Prevent breakfdown dopamine by MAOb

Can have intersctiosn with some antidepressants

Question 19

Essential tremor vs PD on dat scan

Answer 19

ET - comma shape

PD - full stop shape

Question 20

Catechol-O-methyltransferase (CONT) inhibitors for PD

Answer 20

Can’t be given alone have to be with levodopa

Question 21

Advanced therapies for PD

Answer 21

• Deep brain stimulation - turn of subthalamic nucleus to reduce stop. One of best treatments for tremor.
• Apomorphine - Dopamine agonist give under skin subcutaneously for when people have fluctuations but respond well to medications
• Duodopa - through cut in tummy wall into stomach with tube into jejunum and continuous drip into bowl

Ecpensive and need to fit right criteria

Question 22

Person with PD

Answer 22

Non-drug treatments and ways to support people.

Question 23

Summary Pathology of huntingtons chorea and parkinsons disease and diagnostic process

Answer 23

Question 24

Important DDx for Huntingtons Chorea and PD and treatments

Answer 24

Question 25

Summary of Hungtintons chorea - pathology, diagnosis, DDx, and treamtnets

Answer 25

• Pathology - Neurodegenerative disease caused by CAG repeat in Huntingtin Gene
• Diagnosis - Clinical suspicion confirmed by genetics
• Important DDx - Lots, FH will guide youm WIlsons disease is good to rule out
• Treatment - supportive focusing on non drug treatment
• Must be patient centred

Question 26

Summary of parkinsons disease - pathology, diagnosis, DDx, and treamtnets

Answer 26

• Pathology - IPD is neurodegenerative disease caused by?? resulting in aggregation of alpha syneuclein and lewy Bodies
• Diagnosis - CLinical diagnosis using uK brain bank critera supported by biomarkers and exclusion of other causes
• Important DDx - ET for tremor, several for Pdism- use brain bank critera to guide you (Vascular, Parkinsons plus, Dementia with Lewy bodies )
• Treatments - supportive bUT very effective and good quality of life for many for many yesrs, both drug and non drug treatment important
• Most be patient centred