Case 7- Parkinson's Flashcards
Where is the primary somatosensory cortex and primary motor cortex found?
Primary somatosensory = postcentral gyrus (behind central sulcus)
Primary motor cortex= precentral gyrus (anterior to central sulcus)
What forms the striatum?
Caudate nucleus
Putamen
What forms the Lentiform nucleus?
Globus pallidus
Putamen
What are the structures of the basal ganglia?
Thalamus
Striatum (caudate nucleus + putamen)
Globus pallidus - internal and external parts
Subthalamic nucleus
Substantia nigra
What pathways provide input to the striatum? What neurotransmitter do they release?
Corticostriatal: from whole cerebral cortex to striatum = glutamergic
Nigrostriatal: from substantia nigra (pars compacta) to the striatum = dopaminergic
What is the basic motor function of the basal ganglia?
communicates back and forth with the cerebral cortex to initiate, inhibit and modulate movement, before information is sent from the cortex to the muscles via the corticospinal tract
What neuropeptides do the direct and indirect pathways contain?
Direct= dynorphin
Indirect= enkephalin
List the steps in the direct pathway
1- Corticostriatal pathway releases glutamate onto putamen to stimulate movement
2- Putamen releases glutamate to globus pallidus internus (GPI)
3- GPI releases GABA onto its own neurones, inhibiting them
4- These neurones release GABA and project to the thalamus, but since they’re inhibited by self neurones this is reduced (IPSP)
5- Thalamus is released from inhibition so is stimulated
6- Increased action potentials sent to cortex, this initiates wanted movements
What are the steps to the indirect pathway?
1: Corticostriatal pathway sends glutamate to the putamen
2- Putamen releases GABA to the globus pallidus externus (GPE)
3- Since the GPE normally inhibits the subthalamic nucleus (STN), inhibiting GPE releases the STN from inhibition
4- STN releases glutamate to GPI
5- GPI releases GABA onto thalamus
6- Thalamus is inhibited
7- Less action potentials sent to cortex, inhibits unwanted movements
What substrate do D2 and D1 receptors effect and what is its role?
Adenylyl cyclase; which is responsible for conversion of ATP into cAMP (cAMP= stimulatory)
Explain how dopamine affects the direct pathway
Dopamine binds to D1 receptors which is associated with G-stimulatory protein, therefore increases action potentials down neurone (potentiates effect of glutamate onto putamen)
= More intense action potentials sent to cortex
Explain how dopamine affects the indirect pathway
Dopamine binds to D2 receptors associated with G-inhibitory protein, this inhibits the putamen which is also being stimulated by glutamate, therefore less GABA is sent to GPE= STN is stimulated, this sends GABA to GPI, which is inhibited so less GABA is sent to thalamus overall = excitatory to cortex
= More excitatory signals to the cortex
What is the overall effect of dopamine on the direct and indirect pathways?
It increases movement:
- Stimulates direct pathway to facilitate desired movement
- Stimulates indirect pathway to inhibit unwanted movement
= Overall more powerful contractions (less inhibition)
How does the cerebellum project to the brainstem?
Superior cerebellar peduncle= connects to midbrain
Middle cerebellar peduncle = connects to pons
Inferior cerebellar peduncle = connects to medulla
What is the role of the archicerebellum (vestibulocerebellum)?
Connects cerebellum to vestibular system: involved in balance, posture and ocular reflexes, mainly fixation on a target
What is the role of the paleocerebellum (spinocerebellum)?
Connected to spinocerebellar tracts: regulates body movements and receives proprioceptive information
What is the role of the neocerebellum (cerebrocerebellum)?
Connected to the cortex via the pons: Involved in planning movements and motor learning, role in muscle activation and visually guided movements
List the 4 deep cerebellar nuclei
Dentate nuclei = largest
Globose
Emboliform
Fastigal
What divisions do the cerebellar nuclei connect to?
Dentate nucleus: neocerebellum (cerebro)
Emboliform and globose: paleocerebellum (spino)
Fastigal: archiocerebellum (vestibulo)
What are the inputs to the cerebellum?
Spinocerebellar tracts: from spinal cord
Vestibular nuclei: in medulla at level of inferior olivary nucleus
Cerebral cortex: via pontine nuclei
What are the outputs from the cerebellum?
Outputs - to deep cerebellar nuclei (mostly dentate) then goes to brainstem, specifically:
- Vestibular nuclei
- Reticular nuclei
- Red nuclei
Some bypass the nucleu and go straight to thalamus (ventral lateral)
What is the motor pathway of the archicerebellum (vestibulo)?
1- input from vestibular nerve - to vestibular nuclei
2- Projects to cerebellar cortex via inferior peduncle
3- Purkenje cells project into fastigal nucleus
4- Fastigal nucleus projects back to vestibular nucleus and reticular nucleus
5- Forms vestibulospinal and reticulospinal tracts
6- Influences posture and movement
What is the motor pathway of the paleocerebellum (spino)?
1- Input from the spinocerebellar tracts, enters cerebellum via inferior peduncle
2- Purkenje fibres project to globose and emboliform nuclei
3- Fibres project to brainstem via superior peduncle
4- Fibres enter red nucleus
5- Forms rubrospinal tract, which descends down spinal cord= regulates movement
What is the motor pathway of the neocerebellum (cerebro)?
1- Input from cerebral cortex, via pontine nuclei
2- Nucleus gives rise to pontocerebellar fibres, enter cerebellum at middle peduncle
3- Purkenje fibres -> to dentate nucleus
4- Fibres project out at superior peduncle
5- Fibres go to ventrolateral nucleus of thalamus
6- Influences movement via corticospinal tracts
Define Parkinson’s disease
Progressive degeneration of dopaminergic neurones within the substantia nigra (pars compacta), leading to reduced dopamine and thus, altered motor movement.
It is a progressive disorder without remission, and presents with asymmetrical symptoms
What is found to accumulate in the brainstem, spinal cord and cortical regions in Parkinson’s disease?
Alpha-synuclein, which forms Lewy bodies as it accumulates
Which part of the substantia nigra contains dopaminergic neurones and dopamine?
Pars compacta
What is the effect of pars compacta nigral cell loss?
Decreased dopamine release going to D1 and D2, which normally help enhance movement in direct pathway and increase inhibition of unwanted movement in indirect pathway
Explain how reduced dopamine can lead to akinesia/ dyskinesia in PD
Overall basal ganglia output is increased, which is inhibitory so increased inhibition of motor regions in thalamus = reduced motor signals to cortex.
> Direct pathway: less dopamine = less stimulatory input, it is underactive (less movement)
Indirect pathway: less dopamine = less inhibitory input of putamen so its just being stimulated (by glutamate), it is overactive (too much inhibition of movement)
= Muscles have significantly less input, the primary cause of akinesia/ dyskinesia
When are symptoms of PD seen?
Once levels of dopamine are 20-40% of normal
What is the classic triad of features with PD?
1: Resting tremor
2: Rigidity (increased muscle tone)
3: Bradykinesia/ akinesia
What is an early sign of PD?
Impairment of dexterity (fine motor skill), i.e. coordination of muscles in eyes, hands and fingers
What other signs/ symptoms can akinesia and dyskinesia lead to?
- Micrographia: handwriting gets smaller
- Shuffling gait: small steps when walking, reduced arm swing
- Difficulty initiating movement, i.e. turning around
- Hypomimia: reduced facial expression (‘mask-like’)
What causes tremor and rigidity in PD?
Imbalance between dopaminergic and cholinergic neurons; cholinergic neurons usually act to oppose dopamine, so with dopamine lowering, ACh is going to increase (inhibits D1 and excites D2)
What type tremor is usually present in PD? When is it more pronounced?
Pill-rolling tremor (unilateral) - looks like they’re rolling a pill between their thumb and finger
More pronounced at rest, improves with voluntary movement
What type of rigidity is usually present in PD?
Cogwheel rigidity: constant resistance to passive movement of the joints, which gives away in small increments and causes a jerky movement. Usually in upper limbs
Lead pipe: resistance to any movement, usually in lower limbs
For the limbs, is ridigity in PD worse on flexion or extension of the joints?
Lower limbs: worse on flexion
Upper limbs: worse on extension
Other than the classic triad of signs, what else may PD patients present with?
- Depression
- Insomnia
- Loss of sense of smell (anosmia)
- Postural instability: hunched over posture, difficulty standing in one place
- Cognitive impairment and memory problems
- Constipation
What signs/symptoms may be present in late-stage PD?
- Problems with chewing and swallowing
- Monotonous speech (hypophonic)
- Slightly slurred speech
Whats the difference between primary and secondary Parkinsonism?
Primary= idiopathic PD (main)
Secondary= either:
- vascular Parkinsonism - developed after a stroke, have problems with memory, sleep, mood and movement
- Drug-induced Parkinsonism - by neuroleptic drugs, but symptoms reside in a few months
Name the 3 Parkinson’s plus syndromes
Multiple system atrophy
Dementia with Lewy bodies
Progressive supranuclear palsy
What is multiple system atrophy and how does it present?
Neurons in multiple systems degenerate, affects the basal ganglia and other areas.
Degeneration of the basal ganglia = PD symptoms, and degeneration in other areas can lead to autonomic dysfunction (urinary continence, postural hypotension, abnormal sweating) and cerebellar dysfunction (ataxia)
What is Dementia with Lewy bodies and how does it present?
Progressive cognitive decline (dementia) with features of PD. Has other symptoms such as visual hallucinations, dellusions, disorders of REM sleep and fluctuating consciousness.
Explain the presentation of progressive supranuclear palsy and give its typical age of onset
Affects eye movement, balance, mobility, cognitive impairment, speech and swallowing. Age of onset = 60-65 years