3 - Extrapyramidal Systems Flashcards
Major contributors to the motor system:
Pyramidal Motor System (direct and indirect)
Planning and initiating voluntary motor movement and muscle tone
Major contributors to the motor system:
Cerebellum
Balance, equilibrium and real time motor adjustment
NO direct projection to the cortical spinal system
Clinical: Voluntary movement disorders (ipsilateral)
Major contributors to the motor system:
Extrapyramidal Motor System
Motor programming–plan, initiate, maintain
Habitual behaviors–procedural learning
NO direct projections to the cortical spinal system
Involuntary movement disorders (contralateral)
Where do Basal Ganglia and Cerebellum nuclei project?
To Thalamus
NOT direct to spinal cord
What connects basal ganglia to thalamus?
What type of signals does it send?
Globus Pallidus
Inhibitory ONLY; levels of this just change
What connects cerebellum to thalamus?
Deep cerebellar nuclei
Substantia Nigra:
Pars Compacta vs Pars Reticularis
Pars Compacta - neurons contain melanin
Parts Reticularis - neurons DONT contain melanin
Clinical:
Hypokinetic vs Hyperkinetic Disorders
Hypokinetic: Parkinson’s
Hyperkinetic: Huntingtons chorea, Ballismus dystonia
Movement disorder is always contralateral to the injury or lesion
Clinical: Parkinson’s Disease
Pathways?
Degeneration of the DA neurons in the SNc
Hypokinetic Disorder
Reduced excitation of the Direct (Go) excitatory pathway = hard to initiate movement
Reduced inhibitory drive of Indirect (No Go) inhibitory pathway = hard to release thalamus from inhibition to start movement
*Both pathways affected
Parkinson’s Disease
Motor Symptoms
Resting tremor
Cogwheel rigidity
Bradykinesia (slowness in movement)
- decreased size of handwriting, loss of voluntary movement
- Unsteady gait, retropulsion
- Speech and swalling disturbances
Parkinson’s Disease
Non-motor Symptoms
Sensory Abnormalities - Olfactory (often 1st), Parathesia (dermal sensation)
Autonomic Dysfunction
Depression/Anxiety/Sleep Disorders
Masked facies and ‘reptillian stare’
Dementia
Akathisia (restlessness)
Clinical: Tremor
General Definition and Differentiating Myoclonus?
Rhythmic or semi-rhythmic oscillating movements that can be fast or slow
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Can differentiate from myoclonus in that tremor has both agonsit and antagonist muscles are activated; resulting in BIDIRECTIONAL movements
Clinical: Essential Tremor
Familial, benign, or senile tremor–most common
Effects upper extremities, head, tongue, lips, and vocal cords
Clinical: Resting Tremor
Occurs when limbs are relaxed and decrease in intensity or disappear when the limb is moved
Usually involves upper extremities, includes pill roll tremor
Clinical: Intention Tremor (Ataxic Tremor)
Produced with purposeful movement toward a target, such as lifting a finger to touch nose
Usually worsens as you get closer to target
Clinical: Postural Tremor
Occurs when the limbs are actively held in position against gravity and disappears at rest
UMN Lesion vs Basal Ganglio Lesion?
Rigity is key
UMN = clasp knife
Basal Ganglia = ratchet like interuptions; Cogwheel Rigidity
Clinical: Parkinson’s Pathology
Synucleinopathy?
Iron?
90% cases unknown origin
Degeneration of DA neurons in the SNc indicated by loss of melanin-containing neurons
Type of proteinopathy caused by protein misfolding and involves presence of Lewy Bodies that positively stain for alpha-synuclein
- - -
Abnormal accumulation of iron in the melanin-containing degenerating neurons
Clinical: Parkinson’s Treatment Strategies
Drugs / Side Effects
Drugs:
Levodopa + carbidopa
MAO inhibitors (slow breakdown of DA)
COMT inhibitors (slow breakdown of L-dopa)
Side Effects:
- Dyskinesia/hypokinesia: on-off phenomena due to high dose followed by decreeasing drug levels
- L-dopa induced dyskinesia after long-term use of L-Dopa
Clinical: Parkinson’s Disease Treatment Strategies
Surgery
Thalamotomy - radiofrequency ablation
Deep Brain Stimulation (DBS) - electrodes implated contralateral; pulse generator provides high-frequency electrical stimulation
Symptoms: Dysarthria and balance
Clinical: Wilson’s Disease
Copper metabolism disease that causes progressive degeneration of the LIVER and BASAL GANGLIA
Present earlier in life (20s)
Symptoms:
Rings in cornea
Wing beating tremor
rigidity, bradykinesia, impaired speech, psychiatric symptoms, abnormal liver panel
Clinical: Huntington’s Disease
Autosomal dominant linked to expansion of CAG triplet repeat sequency
Progressive Striatal Neurodegenerative Disease
Targets: Striatum (caudate/putamen), particularly enkephalin-containing neurons in indirect pathways
***Net effect is INCREASED thalamic EXCITATION due to REDUCED INHIBITION through the Indirect pathway***
LOSS OF CONTROL OF INDIRECT PATHWAY
Clinical: Huntington’s Disease Symptoms
Hyperkinetic Disorder that includes all 4 basal ganglia functions (movement, eye control, emotion, cognition)
Symptoms show 30-40
Symptoms:
Choreiform Movement
Athetosis
Psychiatric disturbances (depression, anciety, OCD, manic-like behavior)
Dystonic posturing
Tics
Dementia
Clinical: Chorea Movements
Fluid or jerky involuntary movements of varying qyality
Can be mistaken for fidgeting
Severe: Frantic, constantly occurring movements that interrupt voluntary movements
Hemi-chorea is observed with contralateral infarct, hemorrghage, tumor, abscess, or focal lesion
Clinical: Athetosis
Slower form of chorea, characterized by continuous, involuntary writing movements that prevent maintains of stable posture
Clinical: Dystonia
Abnormal or distorted posturing of the limbs, trunk, or face due to sustained contraction of muscles (Charlie Horse)
Painful; can result in hypertophy
Can be generalized (whole body), unilateral, or focused
Clinical: Tics
Example?
Urge to perform a sudden brief action
Motor tics: face, neck, eye blinks, and less often in extremities
Vocal tics: brief grunts, coughing barking
Example: Tourette’s Syndrom
Clinical: Ballismus
Wild flinging movement of the extremities
Subthalamic Nucleus Lesion, results in net INCREASE in thalamic EXCITATION due to REDUCED INHIBITION via the INDIRECT PATHWAYS = HYPERKINETIC effect
Clinical: Hemiballismus
Unilateral (contralateral to lesion) flinging movements to to unilateral lesion to one subthalamic nucleus
Usually Stoke, hemorrhage, tumor, infection, or inflammation
Clinical: Causes of Disease of Direct/In Direct Pathway
Stroke/Infarct
Anterior and Middle Cerebral Arteries supply Striatum
Anterior Choroidal Arteries supple the striatum
Posterior Cerebral Artery supplies the SN
Clinical: Causes of Disease of Direct/In Direct Pathway
Medication
D2 Antagonists (no-go, inhibitory) such as anti-psychotics can result in irrecversible development of tardive dyskinesia
(involuntary movement of the tongue lips, face, trunk, and extremities)
Clinical: Causes of Disease of Direct/In Direct Pathway
Other Causes
Tumor
Carbon Monoxide Poisoning
Pesticides
What is the rough transmission of neural signals through the body movement loop?
Cortical Input ->
Striatum ->
Pallidum ->
Thalamus ->
Cortical Input: Motor, Premotor, Somatosensory
Striatum: Putamen
Pallidum: Lateral Globus Pallidus, Internal Segment
Thalamus: Ventral Lateral, and Ventral Anterior Nuclei
Cycles back to cortical targets
What separates the Striatum/Neostriatum?
What compromises the Neostriatum?
Separated by the internal capsule
Neostriatum = Caudate + Putamen
What comprises Lentiform Nucleus?
Lentiform Nucleus = Putamen+Globus Pallidus
What comprises the Corpus Striatum?
Corpus Striatum =
Caudate+Putamen+Globus Pallidus
*Principle component of the extrapyramidal system*
What are GPe and GPi?
Globus Pallidus External, Globus Pallidus Internal
Globus Pallidus allows Basal Ganglia to send inhibitory signals to the Thalamus
Neurotransmitters:
Major Input + Type?
Major Output + Type?
Input:
Glutamate (excitatory)
Dopamine (modulatory)
Output:
GABA (inhibitory)
What is the main neurotransmitter of the following:
Cortico-Striatal Pathway
Nigro-Striatal Pathway
Thalamo-Striatal Pathway
Cortico-Striatal = Glutamate (excitatory)
Nigro-Striatal = Dopamine (modulatory)
Thalamo-Striatal = Glutamate (excitatory)
What can be said for the activity of GPi (Globus Pallidus Internal) neurons?
They are inhibitory and tonically active (No-Go Indirect path)
Direct Pathway - GO
Travel Path?
Net Effect?
Neurotransmitter + Receptor
End Result
Travel: Striatum direct to Globus Pallidus Int. (GPi) or Pars Reticularis (SNr)
Net: Facilitates Movement; excitations through thalamic connections to motor/pre-motor cortex
NT / RX: Dopamine + D1-receptors (excitatory)
**DECREASE Direct = Decrease GO = INCREASE Inhibition (Thalamus) = LESS movement**
Indirect Pathway - NO GO
Travel Path?
Net Effect?
Neurotransmitter + Receptor
End Result
Travel: Striatum direct to Globus Pallidus Ext. (GPe) and Subthalamic nucleus to Globus Pallidus Int. (GPi) or Pars Compacta (SNc)
Net: Inhibits movement through thalamic connections to motor/pre-motor cortex
NT / RX: Dopamine + D2-receptors (inhibitory)
**DECREASE Indirect = Decrease NO-GO = DECREASE Inhibition (Thalamus) = MORE movement**
What three nuclei make up the corpus striatum?
Caudate
Putamen
Glubus Pallidus
What are 3 incoming projections to the neostriatum and what neurotransmitter do they use?
- Cortico-Striatal: Glutamate (+)
- Nigro-Striatal: Dopamine
- Thalamo-Striatal: Glutamate (+)
What are two major outputs from the neostriatum and what neurotransmitters do they use?
- Glubus Pallidus - Thalamus
- Neostriatum - SNr
Both NT’s are GABAergic Inhibitory
Are D1 or D2 receptors excitatory and what is this kind of neuron?
D1 = Excitatory
Neurotransmitter = Dopamine
D2 = Inhibitory
Neurotransmitter = Dopamine
Medium Spiny Neurons
What is the Parkinson’s Triad of Symptom, and what nuclei are affected?
- Resting tremor
- Cogwheel Rigidity
- Bradykinesia (slowness in movement)
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Dopaminergic Neurons from SNc
What symptoms differentiate PD, Wilson’s and Huntington’s
Parkinson’s: Olfactory dysfunction, Reptillian stare, speech/swalling
Wilsons: Wing Beating, Corneal Rings
Huntington: Choreiform movement, Tics
