Motor Control Disorders

Question 1

what are the basal ganglia and cerebellum do?

Answer 1

regulate planning and execution of movement

Question 2

what is the basal ganglia?

Answer 2

a series of interconnected structures in the brain

Question 3

describe basal ganglia circuitry…

Answer 3

parallel direct and indirect pathways

Question 4

what is the direct pathway of the basal ganglia?

Answer 4

facillitates movement by focusing and amplifying circuits involved in movement.
the direct pathway is activated by dopamine binding to D1 receptors

Question 5

what is the indirect pathway of the basal ganglia?

Answer 5

the indirect pathway aims to inhibit movement via inhibitory cascade in the putamen to gpe and gpi
this pathway is inhibited by dopamine binding to D2 receptors on neurons

Question 6

what is parkinsons disease?

Answer 6

a progressive movement disorder that occurs mainly in the elderly

Question 7

what are the symptoms of parkinsons?

Answer 7

tremor at rest
akinesia
bradykinesia 
rigid
mask expression

Question 8

what are the causes of parkinsons disease?

Answer 8

most are idiopathic (meaning the cause is unknown)

there are some rare hereditary forms and ennvironmental factors can also contribute

Question 9

what is the ‘case of the frozen addicts’?

Answer 9

heroin addicts in the 80s developed severe PD following treatment with a heroin substitute called MPTP
within the body the MPTP was converted into the toxic substance MPP+ (by dopamine) and this was taken up by dopamine transport systems and killed DA neurons

Question 10

what are the key pathophysiological traits of parkinsons disease?

Answer 10

losing neurons from substantia nigra and losing dopaminergic input to the basal ganglia

Question 11

how can we harness the DA pathway to treat PD?

Answer 11

must consider: DA synthesis, metabolism, receptors, and DA uptake and transport

Question 12

why cant we treat PD patients with dopamine?

Answer 12

it is too large and cannot cross the BBB

Question 13

what is the first line treatment for PD?

Answer 13

L-DOPA, and the decarboxylation occurs rapidly and lead to synaptic flooding of exogenous DA

Question 14

what are the side effects of L-DOPA?

Answer 14

dyskinesia (involuntary writhing movements)
on-off effect (rapid fluctuatons between symptomatic and non-symptomatic states)
acute side effects (occuring short term following beggining of drug intake)

Question 15

what are the key components in dopamine metabolism?

Answer 15

DA is broken down via two pathway: the Monoamine oxidase pathway and the catechol-o-methyl transferase inhibition pathway

Question 16

what are two further treatments for PD?

Answer 16

deep brain stimulation

neural transplantation

Question 17

what is Huntington’s disease?

Answer 17

a progressive neurodegenerative disease that present a midlife onset and life expectancy of 15-20 years, following diagnosis

Question 18

how is huntingtons caused?

Answer 18

via genetic and inherited in an autosomal dominant fashion

there is a mutation in the huntington gene affecting number of CAG repeats (36+ = disease)

Question 19

what are the symptoms of huntingtons disease?

Answer 19

motor (including chorea, slurred speech, dystonia, dysphagia)
cognitive impairment (including impaired executive function)
psychiatric/behavioural (including anxiety and depression)

Question 20

what is the pathology of huntingtons?

Answer 20

cell loss in caudate and putamen
GABAergic spiny neurons most at risk (these are inhibitory neurons)
an overactivation of the direct pathway

Question 21

what is hemiballismus?

Answer 21

a rare movement disorder characterised by involuntary violent fliniging motions

Question 22

what causes hemiballismus?

Answer 22

lesions to the subtahalmic nucleus of the basal ganglia

Question 23

what is the pathophysiology of hemiballismus?

Answer 23

loss of excitatory neurons in the GPI

Question 24

what are the treatment options for huntingtons disease and hemiballismus?

Answer 24

use of anti-dopaminergic drugs, including dopamine receptor antagonists and VMAT inhibitors