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.
what are the red flags that do not point towards parkinson’s disease
Rapid gait impairment requiring wheelchair use within 5y;
No progression of motor symptoms / signs over >5y;
Marked bulbar dysfunction within 5y;
Inspiratory respiratory dysfunction;
Severe autonomic failure within 5y;
Recurrent (>1/y) falls because of impaired balance within 3y;
Dystonic anterocollis within 10y;
Absence of non-motor features within 5y;
Unexplained pyramidal signs or symmetrical presentation.
what are the investigations carried out for
If patient comes with tremor:
Bloods- thyroid function tests, copper/caeruloplasmin
Structural Imaging
- CT/MRI scan (normal in PD)
- Abnormal in vascular parkinsonism, parkinson plus disorders
Functional Imaging
- DATSCAN SPECT (FP-CIT spect) is abnormal in degenrative parkinsonism
What happens in to Datscan spect/ FP-CIT SPECT in Parkinson’s Disease?
Asymmetrical loss of dopaminergic neurones
look at pics
what is the pharmalogical and clinical aim regarding PD
Pharmalogical:
to restore dopamine levels
Clinical:
To improve motor symptoms/ improve Quality of life (no evidence for neuro-protection)
What are the PD drug classes
L-dopa
Dopamine agonists
MAO-B inhibitors
COMT- inhibitors
How is L-DOPA prescribed and what 2 preparation is it available in
- L-dopa + carbidopa = Sinemet®
- L-dopa + benserazide = Madopar®
Dosing: 200 – 1000mg / day, across 3-5 doses
Higher dosage results in earlier motor complications, so Start with a low dose and reduce overall L-dopa dose
why are carbidopa and benserazide precribed with L-dopa
Carbidopa- inhibit peripheral metabolism of levodopa, allows a greater proportion of peripheral levodopa to cross the blood–brain barrier for central nervous system effect.
Benseraizde- prevents peripheral metabolism of levodopa
what are the adverse effects of L-dopa
Peripheral: Nausea, vomiting, postural hypotension
Central: confusion, hallucinations
Give examples of Dopamine agonists and list the side effects
Ropinirole, Pramipexole, Rotigotine, Apomorphine
SIde effects:
Dopaminergic side effects
Daytime somnolence
Impulse control disorders (eg. pathological gambling, hypersexuality)
Compare Dopamine agonist to L-dopa (half-life, efficacy, complications)
Longer half-life than L-dopa
Less efficacious than L-dopa
Fewer motor complications than L-dopa
Can be used as monotherapy in early PD or alongside L-dopa as disease progresses
what 2 enzyme inhibtors are used for PD disease and what is the purpose of enxyme inhibitors
Lengthen the time it takes for L-dopa to metabolise
MAO-B inhibitors e.g. Selegiline, rasagline
COMT inhibitors e.g. Entacapone, Opicapaone
Describe MAO-B inhibtors and COMT inhibitors
MAO-B inhibotrs:
- can be precribed as monotherapy in early disease or as adjuctant later
- well tolerated
COMT inhibtors:
- results in longer L-dopa half life
- co precribed with L-dopa
- side effects: dopaminergic + diarrhoea
what are the other medications for PD, why and name their side-effects
Amantadine
Prescribed for anti-dyskinetic effect
Side effects - confusion and livedo reticularis (skin discolouration)
Anticholinergics
Examples: trihexyphenidyl, orphenadrine, procyclidine
Prescribed for anti-tremor effect
Side effects: confusion, urinary retention, blurred vision, dry mouth
Botulinum toxin
Roles in sialorrhoea, blepharospasm / eyelid-opening apraxia, other focal dystonia
what are the motor, axial and cognitive problems in advanced PD
Motor:
Motor complications
‘On /off’ fluctuations
L-dopa-induced dyskinesia
Axial: Gait difficulties (including gait freezing) Change in posture Poor balance / falls Speech / swallowing difficulties
Cognitive:
Dementia
Hallucinations / psychosis
what parts of multidisciplinary team is involved in care of PD
GP Neurologists and care of elderly physician Parkinson's disease nurse specialist Physiotherapist Speech and language therapist Psychiatrist Psychologist Occupational therapist Palliative care team Neurosurgeon
what are the treatment options in advanced PD
Apomorphine pen injections or subcutaneous pump- liquid form of L-dopa pumped into duodenum
Intrajejunal duodopa infusion
Deep brain stimulation surgery
describe brain stimulation surgery
DBS allows electrical stimulation of target nucleus (most commonly STN)
DBS provides a targeted, adjustable, non-destructive, and reversible way of modulating pathological brain circuits
3 implantable components:
Brain leads (containing electrodes at distal end)
Neurostimulator (AKA Implantable Pulse Generator / IPG)
Extension wires
If medication is suddenly taken away then PD emergencies occur, what are these?
Motor- severe OFF periods/ severe dyskinesia, Parkinson-hyperprexia syndrome
Non motor- acute psychosis, impulsivity, dopamine dysregulation, dysautonomia,
Falls
Device related- DBS, apomorphine
