Parkinson's Flashcards
what is alpha- synuclein responsible for?
Parkinson’s
Dementia with Lewy Bodies
Multi System Atrophy
what is Tau responsible for?
Progressive Supranuclear Palsy
Corticobasal degeneration
what are the fundamentals of PD?
clinical presentation depends on the population of neurones affected
progressive
aggregates of misfolded proteins and protein deposition
What is the UK incidence of PD?
0.1-0.2% of the UK pop
roughly 145,000
how many people does PD affect globally?
5 million
what are the complications of PD?
motor impairment autonomic dysfunction cognitive impairment sleep disturbance GI problems incontinence pain
what happens in the substania nigra (with LB)
severe neuronal loss
what are the symptoms of PD?
resting tremor, rigidity, bradykinesia, gait disturbance, masked face, less blinking, freezing gait, micrography
what does MRI/ CT show?
can show the disturbances
what happens when there is a dopamine deficiency?
overactivity of indirect pathway and more GABA - excessive inhib of motor thalamus
what are the three pharmacological options for treatment
L -DOPA (4x daily)
carbidopa ( inhib peripheral metabolism of levodopa)
MAO-B inhib (selegiline, rasagiline) - prvents L- DOPA removal
what happens over long periods of time using pharmacological treatment
it wears off and gradually becomes more ‘off’
what are the side effects of PD treatment?
dskinesia (invol movement), hedonia, impulsivity, freezing of gait
what surgical interventions can be used to treat PD?
subthalamic deep brain stimulation
globus pallidus DBS
what happens during rapid eye movement sleep disorder?
dream enactment
excessive daytime sleepiness
increased psych problems
how many PD patients experience rapid eye movement sleep disorder?
15-35%
what happens during autonomic disorders?
orthostatic hypotension
GI disturbances
how many people are affected with autonomic disorders?
50-85%
how mnay PD patients experience a lower UTI?
20-60%
what are the side effects of anticholinergics?
‘turn off all the taps’
- dizziness, light headed, dry mouth, blurred vision, urinary retention
what percentage of PD patients experience memory problems within 5yrs of diagnosis?
50%
How common is depression among PD patients?
around 80%
what types of PD are classed as atypical?
multi-system atrophy (MSA)
progressive supranuclear palsy
corticobasal degeneration
what are the features of atypical PD?
gait dsyfunction/ postural instability axial rigidity no tremor prominent autonomic dysfunction poor response to L- DOPA early speech problems - dysphonia
what happens during MSA?
cerebellum, pons and basal ganglia are affected
alpha synuclein pathology in neurones, oligodendrocytes+ astrocytes
how many people in the UK have MSA?
3000
how many progressive supranuclear palsy cases are there in the UK?
4000
what pathology does PSP and CBD have?
tau
What haplotype on the MAPT locus is associated with AD, PSP and CBD?
Hap1C
what are classic clinical features of PSP?
downward gaze (damage to oculomotor nucleus), prominent stare, backward falls, neck hyperreflexia, dsyphonia, dsyphagia
what are the classical features of corticobasal degeneration?
cognitive/ memory problems, apathy, anhedonia, phantom limb, paraesthesia, myoclonus movements, rapid decline
how many cases of CBD are there in the UK?
200-500 cases
what would tilavonemab do?
vaccination to clear protein accumulation - stop prions in LB and prevent tau in PSP, CBD
what is hedonia?
excessive happiness which can block the feeling of pain
what year is the study assessing levodopa and the progression of parkinsons?
2004
how is parkinsons characterised by?
the loss of pigmented dopaminergic neurones in the substania nigra
what is levodopa?
replacement therapy that ameliorates the symptoms of the loss of doperminergic neurones
what is levodopa?
replacement therapy that ameliorates the symptoms of the loss of doperminergic neurones
what was previously thought about levodopa and dopamine?
that the reaction between the two caused a build up of ROS and then quickened residual dopamine neuronal loss
what did levodopa show within animal studies?
that it is non toxic and promotes functional recovery of damaged nigral neurones
when did levodopa get approval to be used within the UK?
1988
what did the 2004 study show about levodopa?
there was no clinical evidence suggesting that levodopa is associated with the worsening of the condition
what is the glial repsonse?
source of trophic factors, protects against ROS and glutamate by deletrious events in the ROS production
what are trophic factors?
they are helper molecules that allows a neurone to make connection’s
how is glutamate linked to PD?
it is implicated in both motor and non-motor PD
what happens after the death or impairment of dopamine producing cells in the substania nigra?
less dopamine produced - affects movement
how many more males are affected than females in PD?
50% more
how does noradrenaline link to PD?
due to the loss of nerve endings, there are less noradrenaline which causes fatigue and alters blood pressure
what are the RF for PD?
age, toxin exposures such as pesticides, heavy metals, head injuries and being male
