Movement Flashcards
Direct Pathway
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
Indirect Pathway
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
Neurotransmitters of each part of the direct/indirect pathway
Cortex (+) Glutamate Striatum (-) GABA GPi (-) GABA SNr (-) GABA GPe (-) GABA STN (+) Glutamate SNc (+/-) Dopamine Thalamus (+) Glutamate
Damage to the STN causes what?
Hemiballismus (contralateral to lesion)
Damage to the substantia nigra compacta causes what?
Indicate how dopamine receptors act on the direct/indirect pathway
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)
Which cells are primarily lost in Huntington’s disease?
Cells in the striatum which are primarily part of the indirect pathway
(too little indirect)
How does tetrabenazine work?
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
MPTP toxicity
Causes drug-induced parkinson’s
Found in street drugs, produced during synthesis of MPPP, a meperidine (Demerol) analogue
Dystonia location in childhood vs adulthood onset
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
First sign of DYT1
Inversion of the foot
Occurs around 10 years of age, then gradually progresses to generalized dystonia
torsin A deficiency
What enzyme catalyzes the rate-limiting step of dopamine synthesis?
Tyrosine hydroxylase
-catalyzes conversion of tyrosine to levodopa
*deficient in autosomal recessive form of dopa-responsive dystonia
Which three disorders are caused by mutations in CACNA1A gene?
Familial Hemiplegic Migraine 1 (FHM 1), Episodic Ataxia-2 (EA 2), and Spinocerebellar Ataxia-6 (SCA 6)
Which channel defects are present in Episodic Ataxia 1 and Episodic Ataxia 2?
EA-1: potassium channel defect (KCNA1 gene)
EA-2: calcium channel defect (CACNA1A gene)
Imaging findings of Fahr’s Disease?
bilateral calcification of the basal ganglia
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
a. dopamine agonists
b. bromocriptine
c. amantadine
d. tolcapone
e. anticholinergics (trihexyphenidyl/benztropine)
Name 3 targets of surgery and DBS for PD
ventral intermediate nucleus of thalamus, GPi, STN
Parkinson-Dementia-ALS complex of Guam may be related to ingestion of what?
cycad nut
Which two conditions are due to a mutation in the PLP1 gene?
Pelizaeus-Merzbacher and X-linked spastic paraplegia type 2 (SPG2)
List 7 secondary causes of periodic limb movement disorder
Uremia
Diabetes
Spinal cord injury
Abnormalities of iron, calcium, potassium, magnesium
List 6 secondary causes of restless leg syndrome
Pregnancy
Kidney failure
Abnormalities of iron, calcium, potassium, magnesium
What is the most common autosomal dominantly inherited ataxia in the US?
What gene is involved?
SCA3 (Machado-Joseph Disease)
CAG repeat in ATXN3 on Chr 14q
Clinical features of Machado-Joseph Disease
bulging eyes, ophthalmoplegia, tongue atrophy, facial fasciculations, amyotrophy
What laboratory abnormalities are seen in Wilson’s disease?
Decreased serum ceruloplasmin
Decreased serum copper
Increased urinary copper
Describe the pathology seen in Wilson’s disease
Alzheimer type I and type II astrocytes (type I more common)
List treatments for Wilson’s disease
triethylene tetramine dihydrochloride, D-penicillamine, ammonium tetrathiomolybdate, zinc, chelation
What are differences between Wilson’s disease and Menkes’ Kinky Hair disease?
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.
What is the defect/pathophysiology in Wilson’s disease?
ATP7B gene on Chr 13q codes for copper transporting adenosine triphosphatase which transports copper from hepatocyte into bile
Which toxins can cause chorea?
carbon monoxide, mercury, organophosphates
What is the treatment for acute dystonic reaction?
Benadryl or Cogentin (benztropine)
What is the treatment for neuroleptic malignant syndrome?
bromocriptine or dantrolene
What is a key finding in serotonin syndrome that distinguishes it from neuroleptic malignant syndrome?
myoclonus
