Intro to Parkinson's Flashcards
what are the roles of the basal ganglia
Initiation of voluntary movement Maintaining Posture Eye movement control Social behaviour and decision making Executive functions- higher cognitive functions that help in planning + organising/ working memory
What are the 2 pathways involved in basal ganglia
Direct pathways
Indirect pathways
Describe the direct pathway
- “go pathway”
- Direct link between striatum (putamen+caudate) and Gpi (Globus pallidus interna)
- Activity in this pathway increases cortical activity
Describe the indirect pathway
- “stop pathway”
- Link between striatum ((putamen+caudate) and Gpi via GPe (Globus Pallidus externa) and STN (subthalamic nucleus)
- Activity in this pathway decreases cortical activity
what effect does dopaminergic input to the striatum have on the direct and indirect pathway
- Promotes the direct pathway via D1 receptors
- inhibits the indirect pathway via D2 receptors.
why is substantia niagra dark
Dopamine is produced here
Melanin is a by-product of dopamine production which darkens the substantia niagra
what is the pathology of Parkinson’s disease
- Loss of dopaminergic neurones within substantia nigra
- Surviving neurones contain Lewy bodies (abnormal aggregation of proteins)
- PD manifests clinically after loss of approximately 50% of dopaminergic neurones (asymptomatic until you have lost 40-50%)
What happens to the direct and indirect pathways in untreated parkinsonian state
Loss of dopaminergic input to the striatum through degeneration of the Substantia niagra:
- decrease direct pathway
- increase indirect pathway
- > overactive STN and GPI
- > inhibits thalamus and decreased corticol output
what are some suggested mechanisms for Lewy body formation and neuronal cell death
oxidative stress, mitochondrial failure, excitotoxicity, protein aggregation, interference with transport, interference with DNA transcription, nitric oxide synthesis, inflammation, apoptosis, deficiency of trophic factors, and infection.
what do lewy bodies stain for
alpha-synuclein and ubiquitin
Describe lewy body progression- BRAAK staging
Stages 1 and 2- lewy body formation in pons, medulla and olfactory nucleus- presymptomatic or pre-motor e.g. loss of smell
Stages 3 and 4- lewy body formation in midbrain and substantia niagra- parkinsonism only becomes evident after extensive nigral damage
Stages 5 and 6- lewy body formation in neocortex (wide spread)- development of PD dementia
what are the clinical features of parkinsonism
Bradykinesia (central motor system)- slowness in initiation of voluntary movement with progressive reduction in speed and amplitude of repetitive actions
And at least one of the following:
Muscular rigidity/ lead pipe rigidity
4-6 Hz rest tremor
Postural instability- makes the patient fall
what are the non motor symptoms of parkinsons disease
Dementia Depression Anxiety Constipation/ GI disturbance Nocturia Erectile dysfunction Excessive salivation Low BP/ postural hypotension Speech difficulties Hallucinations Sweating/ Seborrheic dermatitis REM sleep behaviour disorder Restless leg syndrome Reduced olfactory function Fatigue Pain and sensory symptoms
What are the other common causes of parkinsonism/ differential diagnosis
Drug-induced: Dopamine antagonist (Antipsychotics/ antiemetics)
Parkinson plus disorders (PSP: Progressive supranuclear palsy and MSA: Multiple system atrophy)
CBD: Corticobasal degeneration
lewy body dementia
vascular parkinsonism
Benign tumour disorders
What is the EXCLUSION criteria for Parkinsons disease
Cerebellar signs- MSA (cerebellar gait, limb ataxia, sustained gaze-evoked nystagmus)
Vertical gaze palsy / slowed downward saccades- PSP
Parkinsonian features restricted to legs for >3y; vascular parkinsonism
Possible drug-induced parkinsonism;
Absence of L-dopa response;
Cortical sensory loss, ideomotor apraxia, or progressive aphasia; CBD
Normal FPCIT SPECT scan.
