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
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