parkinsons

Question 1

parkinsons

Answer 1

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)

Question 2

types of parkinsons

Answer 2

idiopathic
familial
other (non-degenerative)
- drug induced
- post-encephalic
- toxins
- trauma

Question 3

risk factors for parkinsons

Answer 3

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

Question 4

what harmful act can DECREASE risk of parkinsons?

Answer 4

smoking

Question 5

basal ganglia

Answer 5

is responsible for coordinating habitual movements – walking, looking around
o Controlling voluntary movements + learning specific movement patterns

Question 6

substantia nigra

Answer 6

produces neurotransmitter called dopamine

-> Dopamine is essential for correct functioning of the basal ganglia

Question 7

pathophysio of parkinsons

Answer 7

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

Question 8

what would be seen if mid brain was cut into sections in Parkinsons and substantia nigra visible

Answer 8

reveal loss of normal black pigment in substantia nigra + locus ceruleus (melanin reduction)

Question 9

parkinsons triad

Answer 9

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

Question 10

parkinsons motor features

Answer 10

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

Question 11

non-motor symptoms of parkinsons

Answer 11

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

Question 12

parkinsons diagnostic criteria

Answer 12

UK PDS brain bank criteria

1. Bradykinesia + at least one of –
   a. Muscle rigidity
   b. 4-6hz rest tremor
   c. Postural instability not causes alternate primary cause
2. Exclusion
   a. History of stroke
3. 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

Question 13

what can be said about tremor dominant parkinsons

Answer 13

tremor-dominant subtype being associated with slower rate of progression and less functional disability

Question 14

neurohistological hallmark of parkinsons

Answer 14

Lewy Bodies

(pigment loss correlates with dopaminergic loss)

Question 15

imaging for parkinsons

Answer 15

SPECT/DaT scan

normal = comma shaped
abnormal = “period” shaped

Question 16

key medications for parkinsons

Answer 16

levodopa (with Peripheral decarboxylase inhibitors – carbidopa / benserazide)

dopamine agonists - bromocriptine, pergolide, cabergoline

SSRIs for depression
Osmotic laxatives for constipation

Question 16

key medications for parkinsons

Answer 16

levodopa (with Peripheral decarboxylase inhibitors – carbidopa / benserazide)

dopamine agonists - bromocriptine, pergolide, cabergoline

SSRIs for depression
Osmotic laxatives for constipation

Question 17

key medications for parkinsons

Answer 17

levodopa (with Peripheral decarboxylase inhibitors – carbidopa / benserazide)

dopamine agonists - bromocriptine, pergolide, cabergoline

SSRIs for depression
Osmotic laxatives for constipation

Question 18

levodopa

Answer 18

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

Question 19

side effects of levodopa

Answer 19

• 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

Question 20

side effects of levodopa

Answer 20

• 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

Question 21

4 main parkinson plus syndromes

Answer 21

progressive supranuclear palsy
multiple system atrophy
cortico-basal degeneration
Lewy body dementia

all present with parkinsonism (resting tremor, rigitidy + bradykinesia) plus additional symptoms

Question 22

progressive supranuclear palsy

Answer 22

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

Question 23

multiple system atrophy

Answer 23

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

Question 24

cortico-basal degeneration

Answer 24

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

Question 25

Lewy body dementia

Answer 25

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

Question 26

drug induced parkinsonism

Answer 26

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

Question 27

Wilsons disease

Answer 27

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

Question 28

management of Wilsons

Answer 28

penicillamine