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neurodegeneration > parkinson's > Flashcards

parkinson's Flashcards

1
Q

describe the epidemiology of parkinson’s disease

A

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

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2
Q

what are the putative factors associated with increased parkinsons prevalence

A

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
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3
Q

what are the putative factors reported to reduce risk of parkinsons disease

A

antioxidants: B carotene, Vit A, C, E
dietary: coffee, tea, niacin

life experience: cigarette smoking, alcohol drinking

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4
Q

what are the most important risk factors for parkinsons disease

A

Age

family history (especially  if onset <50)
10-15% cases familial

race- white

protective? cigarettes, coffee

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5
Q

which genes have been implicated in parkinsons? (5%)

A

alpha-synuclein- SNCA

Parkin (PRKN)

leucne-rich repeat kinase 2 (LRRK2)

PTEN-Induced Kinase 1 (PINK1)

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6
Q

what do alphasynuclein aggregates form?

A

lewy bodies

chiefly in motor and occulo motor

associative limbic orbitofrontal pathways

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7
Q

what are the classical features of parkinsons

A

tremor:

rigidity

bradykinesia -variable

cogwheel ridigity- (temor+rigidity)

postural instability

dystonia

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8
Q

what are the features of tremor in parkinsons

A

typically asymmetrical
pill rolling
3-5hz
resting, decreases on action

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9
Q

what are the features of rigidity in parkinsons

A

‘lead pipe’
limbs
axial

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10
Q

what are the features of gait disturbance in parkinsons

A

stooped posture

shuffling

reduced arm and leg swing

require initiatin-visual cues

freezing

poor turning

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11
Q

what are some additional clinical features of parkinsons

A

mask like face

micrographia

postural instability

autonomic disturbances

fluctuation

variability

sleep disturbances

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12
Q

what are the early features of PD

A

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

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13
Q

what are some autonomic disturbances of PD

A

constipation, sweating abnormalities, sexual dysfunction, seborhheic dermatitis

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14
Q

what are some late features of PD

A

progressive rigidity,

postural instability (impaired balance, falls)

depression

parkinsons dementia
(fluctuating ability, psychosis)

fluctuating symptoms
on off/ freezing, diskinesias

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15
Q

what is the average time that L-DOPA is effective before complications?

A

3-5 years

on-off dyskinesia

l dopa resistant symptoms

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16
Q

describe the UK PDS brain bank criteria

A

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

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17
Q

list some criteria that could exclude from the british brain bank criteria

A

history of repeated strokes

repeated head injury

antipsychotic or dopamine depleting drugs

more than one affected relative

18
Q

three or more of the following are required to diagnose definite PD

A

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

19
Q

what are some differential diagnoses for PD

A

essential tremor

external induced disease : drugs: antipsychotics, brain injury

vascular disease

Wilson’s disease

Huntington’s disease

functional symptoms

20
Q

what are the parkinson plus syndromes?

A

parkinsonism plus other features

supranuclear palsy
lewy body disease 
multisystem atrophy
corticobasal degeneration
MND-FTD
21
Q

what are some classic signs of lewy body disease

A

dementia preceeding or within one year of motor features

night time hallucinations

fluctuating confusion

visual hallucinations

perceptual deficits

myoclonus

22
Q

what are the theories regarding visual cues

A

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

23
Q

what factors may lead to cell loss in substantia nigra in PD?

A

susceptibility factors,

parkinsons genes,

mitochondrial dysfunction,

oxidative stress,

risk factors, toxins and environmental factors

24
Q

what genes have been associated with familial PD

A 
parkin (10-20%), 
PINK1 (2-7%) 
DJ1 (1-2%) 
LRRK2 (5-10%) 
SNCA (<0.5%)
25
Q

what genes have been associated with sporadic PD

A

LRRK2 (2%) Parkin , Pink1 , DJ1

26
Q

what genes have GWAS studies shown to be major areas of susceptibility

A

SNCA, MAPT, LRRK2

27
Q

what are the potential mechanisms for PD pathogenesis?

A

oxidative stress,

protein aggregation,

autophagy,

mitophagy,

mitochondria dysfunction

28
Q

describe the proposed oxidative stress role in PD

A

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

29
Q

describe protein aggregation in PD

A

kkkkkkkkk

30
Q

what are the two types of autophagy that may lead to PD:

A

bulk autophagy and ubiquitin proteasome (selective)

31
Q

what are the most common non-motor symptoms of parkinsons

A 
mood problems
sleep problems
cognitive disturbances
impulse control
autonomic dysfunction
presymptomatic symptoms
32
Q

what are four pre-symptomatic non motor symptoms of PD?

A

anosmia

sleep (insomnia, REM sleep restless leg )

depression
pain

33
Q

describe sleep disturbances in PD

A

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

34
Q

restless leg syndrome in PD

A

associated with iron deficiency, drugs, periodic limb movement disorder

treatment: same as parkinsons

dopamine agonists, sedatives, narcotirs, clonazepam

35
Q

depression in PD

A

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

36
Q

anxiety in PD

A

generalised anxiety disorder, anxiety attacks, OCD

no existing treatment studies

sometimes low doses of benzodiazepines (beware of cognitive side effects & changes in balance/gait)

37
Q

psychosis in PD

A

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

38
Q

what features can occur in impluse control disorders

A

pathological gambling

binge eating

compulsive shopping

hypersexuality/paraphilias

punding/hobbyism

(thing people go to vagas for) + punding

39
Q

which drug may be useful for treatment for punding?

A

amantadine

kashihara 2008

40
Q

how can autonomic disturbances be treated?

A

postural hypotension:
midodrine, ephedrine

urinary frequency: anticholinergics

hypersalivation- hyoscine ,botulinium

neurodegeneration (15 decks)

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