Movement Disorders

Question 1

what are the two models of motor dysfunction in basal ganglia?

Answer 1

Rate models: amount of movement and kinematic parameters are determined by the firing RATES of neurons in basal ganglia, thalamus, cortex
Oscillation models: oscillatory changes in BG- thalamocortical circuits contribute to changes in motor activity (firing PATTERN)

Question 2

what are the four characteristic of Parkinson’s disease?

Answer 2

tremor at rest
Akinesia (freezing in front of edges, decreased arm swing etc)
Bradykinesia (slowing of activies of daily living)
Rigidity

Question 3

what is the biochemical principle of Parkinson’s disease? What is it/is it not correlated with?

Answer 3

Dopamine depletion in SNc

dopamine loss results in changes in neuronal firing rates and firing pattern in the basal ganglia

Loss of dopamine is correlated with parkinsonism (tremor, akinesia, rigidity) but not with other issues (dementia, balance problems etc)

Question 4

describe rate model for Parkinson’s

Answer 4

striatal dopamine depletion > increased basal ganglia output > inhibition of thalamic and cortical activity > akinesia/bradykinesia

pathway (optional):
SNc no longer acts on striatum (excite D1, inhibit D2) > Indirect pathway increased, direct pathway inhibited > GPe inhibited > STN excited > GPi/SNr excited > Thalamus inhibited > cortex inhibited > mvt inhibited

Question 5

describe oscillatory model of Parkinson’s

Answer 5

increased beta-gamma phase-amplitude coupling in M1 LFPs in Parkinson’s Disease (the activity of beta depends on the phase of gamma oscillation)

optional:
In normal patient, beta band is desynchronized before movement and synchronized after movement; gamma band is synchronized before movement and desynchronized after movement
In Parkinson patients, this is flipped.
This may result in akinesia (freezing, decreased arm swing)

Question 6

cause of drug-induced dyskinesias

Answer 6

replace dopamine loss with too much D2 activation, GPi less inhibitive, disinhibit the thalamus

Question 7

describe picture of hemiballismus

Answer 7

often due to lesion of STN

Indirect pathway no longer active
less direct pathway inhibits GPi/SNr > GPi/SNr don’t inhibit thalamus as much > thalamus activity increased > cortex activity increased > movements increased

Question 8

describe pathology of Huntington’s disease

Answer 8

trinucleotide repeat disease

early: loss of indirect pathway neurons in striatum (genetic)
late: extensive cortical atrophy

Question 9

describe picture of Huntington’s (not in lecture)

Answer 9

Indirect pathway deteriorates
GPe strongly inhibits STN (and GPi/SNr) > STN no longer excites GPi/SNr
Thalamus no longer inhibited by GPi/SNr > more movement

Question 10

describe clinical manifestation of Huntington’s

Answer 10

First, chora (hyperkinetic), then parkinsonism (hypokinetic)

Question 11

what is the current prominent treatment of Huntington-induced chorea

Answer 11

Make patient slightly parkinsonian (Dopa receptor blockers) to stop movements, induce hypokinesia

Question 12

what are clinical features of dystonia?

Answer 12

Slow, sustained involuntary muscle contractions, abnormal poses (writer’s cramp)

Question 13

what is the pathway of dystonia?

Answer 13

Low levels of cortical inhibition
Abnormal mapping in sensory/motor cortices
Dopaminergic dysfunction

Question 14

characteristic of movement disorders

Answer 14

1. presence of abnormal or excessive movements
2. no impairment of consciousness
3. no weakness

Question 15

classification schemes

Answer 15

1. hyperkinetic vs hypokinetic
2. primary vs secondary
3. focal vs generalized

Question 16

hyperkinetic vs hypokinetic

Answer 16

hypokinetic: parkinsonism
hyperkinetic:
drug-induced dyskinesias
hemiballismus
Huntington's disease

Question 17

Parkinson’s disease etiology

Answer 17

genetics: PARK1 (mutated gene codes for protein alpha-synuclein) and PARK8 (caused by mutation in LRRK2, most common genetic form of PD)
environmental:
toxic:

Question 18

treatment of movement disorders

Answer 18

symptomatic:
Parkinsonism - repalcement of dopamine
Chorea, Ballismus:dopamine receptor antagonists, VMAT blockers
surgical treatment can be used for advanced symptoms
other symptoms are being treated as they arise