parkinson's Flashcards
describe the epidemiology of parkinson’s disease
1% of people over 65
105-178 per 100,000
median age of onset 60
slighty> males
slightly> white
1 in 10 diagnosed under 50
median onset to death 15 yrs
what are the putative factors associated with increased parkinsons prevalence
demographic:
elderly age
male
white
Genetic:
family history of PD or essential tremor
life experience:
head trauma
emotional stress
dietary: animal fat consumption
infectious: HIV, HSV, measles, mumps, japanese encephalitis B
envrironmental rural living farming activity well-water drinking neurotoxin-MPTP pesticide exposure metal exposure: lead, magnesium
what are the putative factors reported to reduce risk of parkinsons disease
antioxidants: B carotene, Vit A, C, E
dietary: coffee, tea, niacin
life experience: cigarette smoking, alcohol drinking
what are the most important risk factors for parkinsons disease
Age
family history (especially if onset <50) 10-15% cases familial
race- white
protective? cigarettes, coffee
which genes have been implicated in parkinsons? (5%)
alpha-synuclein- SNCA
Parkin (PRKN)
leucne-rich repeat kinase 2 (LRRK2)
PTEN-Induced Kinase 1 (PINK1)
what do alphasynuclein aggregates form?
lewy bodies
chiefly in motor and occulo motor
associative limbic orbitofrontal pathways
what are the classical features of parkinsons
tremor:
rigidity
bradykinesia -variable
cogwheel ridigity- (temor+rigidity)
postural instability
dystonia
what are the features of tremor in parkinsons
typically asymmetrical
pill rolling
3-5hz
resting, decreases on action
what are the features of rigidity in parkinsons
‘lead pipe’
limbs
axial
what are the features of gait disturbance in parkinsons
stooped posture
shuffling
reduced arm and leg swing
require initiatin-visual cues
freezing
poor turning
what are some additional clinical features of parkinsons
mask like face
micrographia
postural instability
autonomic disturbances
fluctuation
variability
sleep disturbances
what are the early features of PD
tremor
subtle decrease in dexterity
decreased arm swing on first involved side
soft voice
decreased facial expression
sleep disturbances
decreased sense of smell
depression or anhedonia
what are some autonomic disturbances of PD
constipation, sweating abnormalities, sexual dysfunction, seborhheic dermatitis
what are some late features of PD
progressive rigidity,
postural instability (impaired balance, falls)
depression
parkinsons dementia
(fluctuating ability, psychosis)
fluctuating symptoms
on off/ freezing, diskinesias
what is the average time that L-DOPA is effective before complications?
3-5 years
on-off dyskinesia
l dopa resistant symptoms
describe the UK PDS brain bank criteria
step 1) diagnosis of a parkinsonian syndrome
bradykinesia and at least one of:
muscular rigidity, rest tremor (4-6hz),
muscular rigidity,
rest tremor (4-6hz),
postural instability unrelated to primary visual, cerebellar, vestibular or proprioceptive dysfunction
list some criteria that could exclude from the british brain bank criteria
history of repeated strokes
repeated head injury
antipsychotic or dopamine depleting drugs
more than one affected relative
three or more of the following are required to diagnose definite PD
unilateral onset
excellent response to levadopa
rest tremor present
severe levodopa induced chorea
progressive disorder
levadopa response over 5 yrs
persistent asymmetry affecting side of onset most
clinical course over 10 years
what are some differential diagnoses for PD
essential tremor
external induced disease : drugs: antipsychotics, brain injury
vascular disease
Wilson’s disease
Huntington’s disease
functional symptoms
what are the parkinson plus syndromes?
parkinsonism plus other features
supranuclear palsy lewy body disease multisystem atrophy corticobasal degeneration MND-FTD
what are some classic signs of lewy body disease
dementia preceeding or within one year of motor features
night time hallucinations
fluctuating confusion
visual hallucinations
perceptual deficits
myoclonus
what are the theories regarding visual cues
gives additional feedback to the brain
visual cues activate specific motor pathways which allow damaged circuits to be bypassed
bypasses basal ganglia
-frontal and cerbellar circuits
what factors may lead to cell loss in substantia nigra in PD?
susceptibility factors,
parkinsons genes,
mitochondrial dysfunction,
oxidative stress,
risk factors, toxins and environmental factors
what genes have been associated with familial PD
parkin (10-20%), PINK1 (2-7%) DJ1 (1-2%) LRRK2 (5-10%) SNCA (<0.5%)
what genes have been associated with sporadic PD
LRRK2 (2%) Parkin , Pink1 , DJ1
what genes have GWAS studies shown to be major areas of susceptibility
SNCA, MAPT, LRRK2
what are the potential mechanisms for PD pathogenesis?
oxidative stress,
protein aggregation,
autophagy,
mitophagy,
mitochondria dysfunction
describe the proposed oxidative stress role in PD
either:
chemical exposure,
age or loss of function mutation in DJ1 may lead to increase susceptibility to oxidative stress,
causes accelerated death of neurons in SN, parkinsons disease
describe protein aggregation in PD
kkkkkkkkk
what are the two types of autophagy that may lead to PD:
bulk autophagy and ubiquitin proteasome (selective)
what are the most common non-motor symptoms of parkinsons
mood problems sleep problems cognitive disturbances impulse control autonomic dysfunction presymptomatic symptoms
what are four pre-symptomatic non motor symptoms of PD?
anosmia
sleep (insomnia, REM sleep restless leg )
depression
pain
describe sleep disturbances in PD
vivid dreams/nightmates
REM sleep behavior (actng out)
hallucinations and delusions at night (awake)
confusion at night (sundowning- feature of advanced PD)
reverse in day/night cycle
restless leg syndrome in PD
associated with iron deficiency, drugs, periodic limb movement disorder
treatment: same as parkinsons
dopamine agonists, sedatives, narcotirs, clonazepam
depression in PD
20-40% for all types of depression (5-10% MDD)
correlates: female, history, younger age on onset, atypical parkinsonism
treatment (evidence poor)
only 3 RCTs
recent meta analysis found no difference in treatments-
antidepressant treatment may lead to serotonin syndrome
anxiety in PD
generalised anxiety disorder, anxiety attacks, OCD
no existing treatment studies
sometimes low doses of benzodiazepines (beware of cognitive side effects & changes in balance/gait)
psychosis in PD
may be drug related, may be PD dementia related
significant therapeutic challenge
hypersensitivity to neuroleptics
complications of Anti psychotics in eldery (mortality)
management:
discontinue drugs: anticholinergics, dopamine agonists,
quetiapine, clozapine
cholinesterase inhibitors
what features can occur in impluse control disorders
pathological gambling
binge eating
compulsive shopping
hypersexuality/paraphilias
punding/hobbyism
(thing people go to vagas for) + punding
which drug may be useful for treatment for punding?
amantadine
kashihara 2008
how can autonomic disturbances be treated?
postural hypotension:
midodrine, ephedrine
urinary frequency: anticholinergics
hypersalivation- hyoscine ,botulinium
