Movement

Question 1

Direct Pathway

Answer 1

Cortex –> Striatum (Caudate and Putamen) –> GPi/SNr –> Thalamus (VA, VL) –> Cortical motor areas

By disinhibiting the thalamus, the direct pathway facilitates the thalamocortical pathway, which is excitatory
*Ultimately results in increased activity of the motor cortex

Question 2

Indirect Pathway

Answer 2

Cortex –> Striatum (Caudate and Putamen) –> GPe –> STN –> GPi/SNr –> Thalamus (VA, VL) –> Cortical motor areas

By providing excitation to the GPi/SNr which is inhibitory to the thalamus, the indirect pathway causes inhibition of the thalamocortical pathway.
*Ultimately results in cortical inhibition

Question 3

Neurotransmitters of each part of the direct/indirect pathway

Answer 3

Cortex (+) Glutamate
Striatum (-) GABA
GPi (-) GABA
SNr (-) GABA
GPe (-) GABA
STN (+) Glutamate
SNc (+/-) Dopamine
Thalamus (+) Glutamate

Question 4

Damage to the STN causes what?

Answer 4

Hemiballismus (contralateral to lesion)

Question 5

Damage to the substantia nigra compacta causes what?

Indicate how dopamine receptors act on the direct/indirect pathway

Answer 5

Parkinson Disease (D1 and D5 receptors excite direct pathway, D2 and D4 receptors inhibit the indirect pathway) –> PD causes decreased activity of direct pathway and increased activity of indirect pathway

(too much indirect, not enough direct)

Question 6

Which cells are primarily lost in Huntington’s disease?

Answer 6

Cells in the striatum which are primarily part of the indirect pathway

(too little indirect)

Question 7

How does tetrabenazine work?

Answer 7

Blocks VMAT2 (vesicular monoamine transporter 2 protein) which prevents dopamine from being released

–> reduces effects of dopamine thereby reducing excitation of direct pathway and inhibition of indirect pathway

Used in Huntington’s Disease

Question 8

MPTP toxicity

Answer 8

Causes drug-induced parkinson’s

Found in street drugs, produced during synthesis of MPPP, a meperidine (Demerol) analogue

Question 9

Dystonia location in childhood vs adulthood onset

Answer 9

Dystonia that begins in CHILDHOOD tends to involve LOWER extremities and may spread

Dystonia that begins in ADULTHOOD tends to involve UPPER body and does NOT usually spread

Question 10

First sign of DYT1

Answer 10

Inversion of the foot
Occurs around 10 years of age, then gradually progresses to generalized dystonia

torsin A deficiency

Question 11

What enzyme catalyzes the rate-limiting step of dopamine synthesis?

Answer 11

Tyrosine hydroxylase
-catalyzes conversion of tyrosine to levodopa

*deficient in autosomal recessive form of dopa-responsive dystonia

Question 12

Which three disorders are caused by mutations in CACNA1A gene?

Answer 12

Familial Hemiplegic Migraine 1 (FHM 1), Episodic Ataxia-2 (EA 2), and Spinocerebellar Ataxia-6 (SCA 6)

Question 13

Which channel defects are present in Episodic Ataxia 1 and Episodic Ataxia 2?

Answer 13

EA-1: potassium channel defect (KCNA1 gene)

EA-2: calcium channel defect (CACNA1A gene)

Question 14

Imaging findings of Fahr’s Disease?

Answer 14

bilateral calcification of the basal ganglia

Question 15

Which drug(s) used in PD can cause:

a. Sudden attacks of sleepiness
b. Pulmonary fibrosis
c. Cardiac arrhythmias
d. Liver toxicity
e. Urinary retention

Answer 15

a. dopamine agonists
b. bromocriptine
c. amantadine
d. tolcapone
e. anticholinergics (trihexyphenidyl/benztropine)

Question 16

Name 3 targets of surgery and DBS for PD

Answer 16

ventral intermediate nucleus of thalamus, GPi, STN

Question 17

Parkinson-Dementia-ALS complex of Guam may be related to ingestion of what?

Answer 17

cycad nut

Question 18

Which two conditions are due to a mutation in the PLP1 gene?

Answer 18

Pelizaeus-Merzbacher and X-linked spastic paraplegia type 2 (SPG2)

Question 19

List 7 secondary causes of periodic limb movement disorder

Answer 19

Uremia
Diabetes
Spinal cord injury
Abnormalities of iron, calcium, potassium, magnesium

Question 20

List 6 secondary causes of restless leg syndrome

Answer 20

Pregnancy
Kidney failure
Abnormalities of iron, calcium, potassium, magnesium

Question 21

What is the most common autosomal dominantly inherited ataxia in the US?
What gene is involved?

Answer 21

SCA3 (Machado-Joseph Disease)

CAG repeat in ATXN3 on Chr 14q

Question 22

Clinical features of Machado-Joseph Disease

Answer 22

bulging eyes, ophthalmoplegia, tongue atrophy, facial fasciculations, amyotrophy

Question 23

What laboratory abnormalities are seen in Wilson’s disease?

Answer 23

Decreased serum ceruloplasmin
Decreased serum copper
Increased urinary copper

Question 24

Describe the pathology seen in Wilson’s disease

Answer 24

Alzheimer type I and type II astrocytes (type I more common)

Question 25

List treatments for Wilson’s disease

Answer 25

triethylene tetramine dihydrochloride, D-penicillamine, ammonium tetrathiomolybdate, zinc, chelation

Question 26

What are differences between Wilson’s disease and Menkes’ Kinky Hair disease?

Answer 26

Menkes’ involves alpha subunit and there is an absorption problem, Wilson’s involves beta subunit and there is a bile problem

Menkes’ has low liver copper, Wilson’s has high liver copper

Menkes’ is treated with copper supplementation, Wilson’s is treated with chelation, D-penicillamine, zinc, etc.

Question 27

What is the defect/pathophysiology in Wilson’s disease?

Answer 27

ATP7B gene on Chr 13q codes for copper transporting adenosine triphosphatase which transports copper from hepatocyte into bile

Question 28

Which toxins can cause chorea?

Answer 28

carbon monoxide, mercury, organophosphates

Question 29

What is the treatment for acute dystonic reaction?

Answer 29

Benadryl or Cogentin (benztropine)

Question 30

What is the treatment for neuroleptic malignant syndrome?

Answer 30

bromocriptine or dantrolene

Question 31

What is a key finding in serotonin syndrome that distinguishes it from neuroleptic malignant syndrome?

Answer 31

myoclonus