PD & Drug Therapy Of Basal Ganglia Disorders Flashcards
Ballismus
- Description
- Pathophysiology
- Causes
A high amplitude flailing of the limbs
Hemiballismus- one side of the body
Pathophysiology
Disruption of the STN
Indirect pathway is not excited so direct pathway is promoted
Cause
Stroke
Chorea -Description -Pathophysiology -Causes .
Jerky, brief, irregular contractions
non-repetitive, non-rhythmic, flow from one muscle to the next
Fidgety, restless
Pathophysiology
-Disruption in STN, indirect pathway is inhibited, direct pathway is promoted
Causes
- Huntingdon’s Disease (degenerative)
- Neuroleptics (antipsychotics)
Tics
- Description
- Exacerbating and relieving factors
Short, repetitive movements with a premonitory urge. Simple movements - blinking, coughing Complex movements - jumping or twirling Plus: motor disorder
Coprolalia (rare): swearing -
Worsened with
- fatigue
- anxiety
Reduced by
- Distractions
- Concentration
Causes of Tic Disorder
Co-morbid conditions
ADHD 50%
OCD 33.3%
Anxiety 50%
Complex genetic inheritance
Post infectious immune
Tourette syndrome
more severe expression of a spectrum of tic disorders
multiple motor tics and at least one phonic tic
Huntington’s chorea
-genetics
Autosomal dominant with complete penetrance
Trinucleotide repeat on chromosome 4
-longer the repeat sequence the earlier the disease presents
Repeat sequence tends to enlarge with each generation
Huntington’s chorea
-clinical presentation
Cognitive
-Inability to make decisions, multitask, slow in thought.
Behavioural
Irritability, depression, apathy, anxiety, delusions.
Physical
Chorea, motor persistence, dystonia, eye movements.
Myoclonus
- Description
- Causes
Quick, brief, involuntary muscle jerk.
Rapid onset and offset
Positive=muscular contractions
Negative=muscular inhibitions
Causes
- Juvenile Myoclonic Epilepsy
- Brain hypoxia
- Prion disease
Describe the pathophysiology of myoclonus
Unknown
1) Possibly an imbalance between excitatory and inhibitory neurotransmitters
(can be treated with antiepileptic drugs)
2) Perturbations of the motor control system leading to a brief disequilibrium
Explain why present at multiple levels e.g cortical, subcortical , spinal etc.
Dystonia
- Description
- Causes
Abnormal twisting posture
(often axial, facial, truncal, associated with jerky tremor)
Causes
Stroke Brain injury Encephalitis Parkinsons disease Huntington’s disease
Dystonia
-pathophysiology
- abnormal activity in the motor cortex, supplementary motor areas, cerebellum, basal ganglia
- Abnormal dopaminergic activity in basal ganglia (dystonia causes by blocking DA receptors, some dystonias are Levodopa responsive)
What is a tremor?
Involuntary, rhythmic, sinusoidal alternating movements of part of the body.
in limbs, head, chin, soft palate
When can a tremor occur?
At rest
Postural (in a particular body position)
Kinetic (when performing an action)
Most common: Essential tremor (simple kinetic tremor)
Describe the pathophysiology of a tremor
Increased activity in the cerebellothalamocortical circuit.
In PD: Dopamine dysfunction in the pallidum results in this.
In Essential Tremors:
GABAergic dysfunction in the cerebllum causes this.
MRI focussed ultrasound therapy
Treatment method for treatment resistant Essential Tremor
-used for PD
What are the drug treatments for tics, chorea, ballismus?
Dopamine (D2) receptor blocking agents
Dopamine depleting agents
Atypical anti-psychotics
Problems with D2 receptors
Acute problems
- Oculogyric crisis
- Neuroleptic malignant syndrome
Subacute problems
-Drug induced Parkinsonism
Long term (tardive) dyskinesias
Oculogyric crisis
Very characteristic acute response to certain drugs
Fixed stare, upward deviation of eyes
Neck and trunk extensions
Jaw spasms +/- tongue protrusion
‘Acute dystonic’ reaction
Tetrad of features of Neuroepileptic malignant syndrome
1) Fever
2) rigidity
3) autonomic instability
4) confusion
Tardive dyskinesia
Clinical Manifestations: chorea, athetosis, dystonia, akathisia, stereotyed behaviours, rarely tremor.
Hypokinetic movement disorders
-Parkinsonism
Symptoms
- Slowness of movement (also thought/ psychomotor retardation)
- Stiffness
- Shaking.
Physical signs include:
- Slowness and poverty of movement (bradykinesia) e.g. loss of facial expression and arm swing, difficulty with fine movements
- Voluntary movements harder to initiate (akinesia)
- Rigidity
- Rest tremor.
What is Parkinson’s Disease?
What is the Histopathological hallmark?
A neurodegenerative condition, primarily affecting dopaminergic cells of the substantia nigra
Histopathological hallmark: Lewy bodies and intraneuronal protein inclusion
Pathophysiology of PD
- Decreased dopamine input to striatum
- reduced activation of direct pathway
- reduced inhibition (higher activity) of indirect pathway
- reduced movements.
Causes of Parkinsonism
Neurodegenerative
-PD
Secondary
- Drugs(haloperidol)
- Hydrocephalus
- Cerebrovascular disease
- Toxicity/ metal deposition disoders
Genetic
- Metabolic - Wilson’s disease (copper deposition)
- Rare familial (dominant/ recessive) causes
What enzyme breaks down Levodopa to Dopamine?
DOPA decarboxylase
Treatment for PD [7]
L-DOPA Amantidine DA agonist COMT inhibitors Anticholinergics MAO-IB Deep Brain Stimulation
DA Agonist
-give 2 examples
L-DOPA
-Gold standard
-Always combined with Dopa decarboxylase inhibitor to prevent peripheral conversion to DA which then can’t cross BBB
Apomorphine
s/c
reduces dyskinesias
COMT inhibitors
- give 2 examples
- side effects
Entacapone/Tolcapone
-worsens dyskinesias, diarrhoea, liver disease (tolacpone)
Anticholinergics
helps with tremors and parkinsonian symptoms
Amantadine
Antiviral
glutamate antagonist
MAO-IB
treatment of PD
Deep Brain Stimulation
For PD, tremous, dystonias
implantable device
directly stimulates STN
