Movement disorders and Parkinson's Flashcards Preview

202: Theme 2, Sensory inputs and motor outputs > Movement disorders and Parkinson's > Flashcards

Flashcards in Movement disorders and Parkinson's Deck (33)
1

Ballismus
- Description
- Pathophysiology
- Cause

High amplitude, flailing limbs.

Hemiballismus- on one side of the body

Pathophysiology
- Disruption in the subthalamic nucleus
- Internal globus pallidus is not excited so direct pathway is promoted

Cause
- Stroke

2

Tics
- Description
- Exacerbating and relieving factors

Short, repetitive movements with premonitory urge.

Simple movements
- Blinks, coughing

Complex
- Jumping, twirling

Plus (with simple/ complex)
- Motor disorder

Coprolalia [rare]
- Swearing

Exacerbated by:
- Anxiety
- Fatigue

Reduced by:
- Distracting
- Concentration

3

Tourette's syndrome

Severe expression of a spectrum of tic disorders

Composed of multiple motor tics and at least one phonic tic

4

Causes of tics

Co-morbidity
- ADHD [50%]
- OCD [1/3]
- Anxiety [up to 50%]

Genetic inheritance
- Involves many genes

Post-infectious immune response

5

Chorea
- Description

Jerky, brief, IRREGULAR contractions
- Not repetitive
- Not rhythmic

Flows from one muscle to the next
- Fidgety, restless

6

Chorea
- Pathophysiology
- Causes

Disruption in the subthalamic nucleus
- Promotes the direct pathway and inhibits indirect pathway

Cause
- Huntington's disease [degenerative]
- Neuroleptics [antipsychotics]

7

Huntington's chorea
- Genetics

Autosomal dominance with complete penetrance [ clinical symptoms are present in all individuals affected by the disease]

Trinucleotide repeat
- Chromosome 4
- Longer repeat sequence = the earlier the disease presents

Repeat sequence tends to enlarge with each generation

8

Huntington's chorea
- Clinical presentation [cognitive, behavioural, physical]

Cognitive
- Inability to make decisions
- Inability to mutli-task
- Slow in thought

Behavioural
- Irritable
- Depressed
- Apathic
- Anxiety
- Delusions


Physical
- Chorea
- Motor persistence [i.e protruding tongue and withdrawing unwilling]
- Dystonia
- Eye movements

9

Myoclonus
- Description
- Causes

Twitching of a muscle or a group of muscles
- Rapid onset and offset

Postive = muscular contractions
Negative = muscular inhibitions

Causes:
- JME
- Brain hypoxia
- Prion disease [CJD]

10

Myoclonus
- Pathophysiology

Not fully understood

Suggested
1. Imbalance between excitatory and inhibitory neurotransmitters

2. Deviation of the motor control system, causing a brief equilibrium

11

Dystonia
- Description
- Causes

Abnormal twisting posture
- Axial
- Facial
- Truncal
Jerky tremor

Causes:
- Stroke
- Brain injury
- Encephalitis
- PD
- HD

12

Dystonia
- Pathophysiology

Not well understood

1. Abnormal activity in:
- Motor cortex + supplementary areas
- Cerebellum
- Basal ganglia

2. Abnormal dopaminergic activity in basal ganglia

13

Tremor
- Action
- Body parts affect
- Classifications

- Involuntary
- Rhythmic
- Alternating movements of part of the body

Parts affected:
- Limbs
- Head
- Chin
- Soft palate

Can occur at rest, at a particular body position [postural] or when performing an action [kinetic]


Most common
- Essential tremor

14

Tremor
- Pathophysiology

Caused by increased activity in cerebellothalamocortical circuit.

In PD
- Dopamine dysfuntion in the pallidum

In essential tremors
- GABAergic dysfunction in cerebellum

15

MRI focussed ultrasound therapy

Treatment method for resistant essential tremors
- Used for PD

16

Drug treatments for tics, chorea and ballismus

D2 receptor blocking agents

Dopamine depleting agents

Atypical antipsychotics

17

Problems caused by D2 blocking agents

Affects the basal ganglia

Acute:
- Oculogyric crisis
- Neuroleptic malignant syndrome

Subacute
- Drug induced Parkinsonism

Long term
- Tardive dyskinesias

18

Oculogyric crisis

Prolonged, involuntary upward deviation of the eyes
- Neck + trunk extension
- Jaw spasm with or without tongue protrusion

Acute side effect of neuroleptics and other D2 blockers

19

Neuroleptic malignant syndrome

Acute reaction to D2 blocking drugs

Features:
- Rigid muscles due to Raised creatine phosphokinase
- Fever
- Autonomic instability
- Confusion

20

Tardive dyskinesia

Long term side effect of D2 blocking agents.

- Choeric oral/facial movements
- Dystonic trunk

Mechanism
- Dopamine sensitivity of basal ganglia ?

Treatment:
- Gradually withdrawal drug
- Substitution with atypcial anti-psychotic
- Dopamine depleting agent [tetrabenazine]

21

Parkisonism

Hypokinetic movement disorders

Symptoms:
- Slow
- Stiff
- Shaky

Signs:
- Bradykinesia
- Akinesia
- Rest tremor
- Rigidity

22

Non motor Parkinsonism symptoms

Mood:
- Depression, anxiety

Dementia

Autonomic:
- Postural hypotension
- Hypersalivation

Sleep disturbance
- Restless legs
- REM parasomnia

Reduced sense of smell

23

Parkinson's disease pathophysiology

Destruction of cells in substantial nigra
- Decreased DA input into the striatum
- Reduced activation of direct pathway
- Reduced inhibition of indirect pathway

24

Histopathological hallmark of PD

Lewy bodies
- Abnormal accumulation of proteins inside nerve cells

25

Parkinsonism causes

Neurodegenerative
- Idiopathic [PD], over 80%
- Diffuse Lewy body disease
- Atypical parkinsonism

Drugs
CVD
Hydropcephalus
Toxicity

Genetic
- Wilson's disease [copper deposits]
- Familial causes

26

MAO inhibitors

Type A: Prevents breakdown of
- Serotonin
- Adrenaline
- NADR
- DA

Type B
- Specific to DA

Non selective, used for:
- Depression
- Has problems with metabolising dietary amines/ tryptophans

Selective [Type B] used for:
- PD

27

L dopa

Precursor of dopamine

Sold as: Madopar, sinemet

Combine with dopa decarboxylase inhibitor to prevent peripheral conversion to dopamine

28

Amantadine

Early PD drug treatment
- Glutamate agonist [initially anti-flu agent]

29

Anti-cholinergics and PD
- Side effect
- Use
- Examples

Originally used to treat and help with tremors

Limited by side effects
- Confusion
- Urinary retention
- Dry mouth

Examples:
- Procyclidine
- Benzhexol

30

Entacapone/ Tolcapone

COMT inhibitor
- Reduces peripheral metabolism of L-dopa

Pros
- Increases L-dopa duration of action and efficacy

Cons:
- Can make dyskinesia worse
- Diarrhoea
- Liver disease [tolcapone]

31

Duodenal L-dopa infusion [Duodopa]

Method of administering L-dopa to the duodenum via infusion pump

Pros
- Can manage motor fluctuations

Cons:
- Expensive
- Does not affect disease progression
- Can be affected by gastric problems
- Unpredictable bioavailability [hard to hit narrow therapeutic window]

32

DA agonists
- Ergot
- Non-ergot
- Cons

Can bypass nigrostriatal neurones

Ergot derived no longer used due to cardiac/ pulmonary fibrosis
- Pergolide
- Carbergoline

Non-ergot:
- Pramipexole
- Ropinirole
- Rotigotine [patch]
- Apomorphine [Subcutaneous]


Cons:
- Dopamine dysregulation syndrome

33

Deep brain stimulation

High frequency stimulation targetted at
- STN [PD]
- Pallidum [Dystonia]
- Thalamus [tremor]

Does not prevent progression or have an effect on non-motor symptoms