parkinsons Flashcards
parkinsons
progressive reduction of dopamine in the basal ganglia - leading to disorders of movement
-> loss of dopaminergic neurons froms the pars compacta region of substantia nigra
(can see this in brain (coloured) as releases melanin)
types of parkinsons
idiopathic
familial
other (non-degenerative)
- drug induced
- post-encephalic
- toxins
- trauma
risk factors for parkinsons
advancing age - greatest
fam history (esp early onset <40yrs)
males
environmental - pesticide exposure, prior head injury, RUral living, beta blocker use
genetic
- LRRK2 (AD)
- PARKIN
- Alpha-synuclein - AD, Lewy bodies
what harmful act can DECREASE risk of parkinsons?
smoking
basal ganglia
is responsible for coordinating habitual movements – walking, looking around
o Controlling voluntary movements + learning specific movement patterns
substantia nigra
produces neurotransmitter called dopamine
-> Dopamine is essential for correct functioning of the basal ganglia
pathophysio of parkinsons
reactive gliosis happens in response to dopaminergic neuron loss -> astrocyte formation
starts at brain stem + ascends up to brain
- advanced = cortical involvement
- pre-motor symptoms = just brain
what would be seen if mid brain was cut into sections in Parkinsons and substantia nigra visible
reveal loss of normal black pigment in substantia nigra + locus ceruleus (melanin reduction)
parkinsons triad
bradykinesia - slow + diminshing movements
rigidity - increased muscle tone, resistance to passive movement, “cogwheel” as you passively flex arm (gives way to small little jerks)
tremor - at rest, unilateral pill rolling
parkinsons motor features
handwriting getting smaller, shuffling gait
difficulty initiating movements - standing still to walking
diffuculty turning - having to take lots of wee steps
reduced facial movement/expressions = hypomimia
tremor worse at rest + if distracted, 4-6Hz (4-6 times a second)
reduced arm swinging
stooped posture, forward tilt
eyes move horizontally v slowly
non-motor symptoms of parkinsons
anosmia
REM sleep disorder behaviour - act out dreams, speak, move
depression, constipation
friendly hallucinations
dementia - must have parkinsons for at least 1yr prior to onset, presentation similar to DLB
parkinsons diagnostic criteria
UK PDS brain bank criteria
- Bradykinesia + at least one of –
a. Muscle rigidity
b. 4-6hz rest tremor
c. Postural instability not causes alternate primary cause - Exclusion
a. History of stroke - Supporting criteria – 3 or more
a. Unilateral onset
b. Rest tremor
c. Progressive syndrome
d. Asymmetry
e. Excellent response to L-dopa
f. Development of L-dopa dyskinesia
g. Sustained L-dopa response > 5yrs
what can be said about tremor dominant parkinsons
tremor-dominant subtype being associated with slower rate of progression and less functional disability
neurohistological hallmark of parkinsons
Lewy Bodies
(pigment loss correlates with dopaminergic loss)
imaging for parkinsons
SPECT/DaT scan
normal = comma shaped
abnormal = “period” shaped
key medications for parkinsons
levodopa (with Peripheral decarboxylase inhibitors – carbidopa / benserazide)
dopamine agonists - bromocriptine, pergolide, cabergoline
SSRIs for depression
Osmotic laxatives for constipation
key medications for parkinsons
levodopa (with Peripheral decarboxylase inhibitors – carbidopa / benserazide)
dopamine agonists - bromocriptine, pergolide, cabergoline
SSRIs for depression
Osmotic laxatives for constipation
key medications for parkinsons
levodopa (with Peripheral decarboxylase inhibitors – carbidopa / benserazide)
dopamine agonists - bromocriptine, pergolide, cabergoline
SSRIs for depression
Osmotic laxatives for constipation
levodopa
Synthetic dopamine to boost dopamine levels
Usually combined with drug that stops it being broken down before reaches brain
* Peripheral decarboxylase inhibitors – carbidopa / benserazide
Most effective Mx for symptoms but becomes less effective over time
side effects of levodopa
- Postural hypotension – give midodrine if bad
- Dry mouth, anorexia, palpitations
- End of dose wearing off – worse symptoms at end of dosage interval
- Greatest symptomatic benefit but longterm is assoc with motor complications
- When dose too high, can develop dyskinesias (abnormal movement assoc with excessive motor activity) examples –
o Dystonia – where excessive muscle contraction leads to abnormal postures or exaggerated movements
o Chorea – abnormal involuntary movements that can be jerking + random
o Athetosis – involuntary twisting or writhing movements usually in fingers, hands or feet
side effects of levodopa
- Postural hypotension – give midodrine if bad
- Dry mouth, anorexia, palpitations
- End of dose wearing off – worse symptoms at end of dosage interval
- Greatest symptomatic benefit but longterm is assoc with motor complications
- When dose too high, can develop dyskinesias (abnormal movement assoc with excessive motor activity) examples –
o Dystonia – where excessive muscle contraction leads to abnormal postures or exaggerated movements
o Chorea – abnormal involuntary movements that can be jerking + random
o Athetosis – involuntary twisting or writhing movements usually in fingers, hands or feet
4 main parkinson plus syndromes
progressive supranuclear palsy
multiple system atrophy
cortico-basal degeneration
Lewy body dementia
all present with parkinsonism (resting tremor, rigitidy + bradykinesia) plus additional symptoms
progressive supranuclear palsy
parkinsonism + vertical gaze palsy - dysfunction of muslce involved in looking upwards
impairment of vertical gaze - down worse than up
-> may complain of difficulty reading or descending stairs
bradykinesia prominent - broadbased stiff gait, falls
tend to present with a more symmetric + tremor negative parkinsonism
multiple system atrophy
rare condition where neurons of multiple system in brain degenerate
affects basal ganglia + other areas
- degen of basal ganglia -> parkinsonism
- degen in others -> autonomic + cerebellar dysfunction
autonomic dysfunction
- postural hypotension, constipation
- sexual dysfunction, abnormal sweating
cerebellar dysfucntion -> ataxia
cortico-basal degeneration
parkinsonism plus spontaneous activity by an affected limb, or akinetic rigidity of that limb - “alien hand syndrome”
- Patients sometimes present with apraxia - the inability to conceptulise movement i.e. description of not being able to follow instructions, but being able to do them automatically
Lewy body dementia
progressive/FLUCTUATING cognitive decline with assoc symptoms of visual hallucinations, delusions, disorders of REM sleep
typically occurs before parkinsonism, but usually both features occur within a year of each other. This is in contrast to Parkinson’s disease, where the motor symptoms typically present at least one year before cognitive symptoms
drug induced parkinsonism
dopamine-blocking or depleting drugs, esp neuroleptics (except clozapine), induce parkinsonism or worsen symtpoms
antimuscarinic drugs reduce these symptoms, although tardive dyskinesia may be made worse
Wilsons disease
autosomal recessive, characterised by excessive copper deposition in tissues, younger onset 10-25yrs (<50y/o)
hepatitis
basal ganglia degeneration
speech, psychiatric problems
chorea, dementia, parkinsonism
blue nails
Kayser-Fleischer rings - green/brown ring round iris
management of Wilsons
penicillamine
