Bb1 Motor Systems 2 Part 2

Front 1

What is the pathogenesis of Parkinson's?

Back 1

Degeneration of the substantia nigra results in the loss of dopaminergic input to the neostriatum. Favors an increase in the activity of the indirect pathway and decreased activityin the direct pathway - lack of disinhibition and an increased inhibition. Overall effect is to decrease the output of thalamic motor neurons to the cortex.

Front 2

What is 'Parkinsonism'?

Back 2

Caused by known factors

Front 3

Parkinson's: pathology?

Back 3

Neurons of the SN develop inclusion bodies called Lewy bodies. Other pigmented neurons in the CNS may contain these inclusion bodies as well.

Front 4

Parkinsons: non major symptoms with cause?

Back 4

Depression
Dementia
Those with dementia may also show a loss of other dopaminergic neurons in the brain involved in the limbic system.

Front 5

What is a genetic mutation that can result in Parkinson's?

Back 5

Point mutation in alpha-synuclein, which is a major component of Lewy bodies.
Increases the formation of intracellular aggregates that arae toxic to neurons and lead to Lewy body formation.

Front 6

List causes of Parkinson's.

Back 6

Encephalitic inflammation of the globbus pallidus and SN
Stroke
CO poisoning
Toxic substances - herbicides and pesticides
Certain drugs
Meth

Front 7

Describe the blood supply of the corpus striatum.

Back 7

Anterior and middle cerebral arteries - caudate and putamen
Posterior cerebral arteries - SN

Front 8

What types of drugs can result in Parkinson's?

Back 8

Neuroleptics = major tranquilizers or anti-psychotic drugs

Front 9

What are the 2 major classes of typical neuroleptics? What is their general MOA?

Back 9

Phenothiazines
Butyrophenones

Decrease dopamine activity by blocking dopamine receptors

Front 10

Why do neuroleptics work by decreasing dopamine activity?

Back 10

Dopamine is a major NT in the limbic system, and overactivity is implicated in psychosis.

Front 11

Chlorpromazine: MOA? side effects?

Back 11

Blocked D2 dopamine receptors

Induced Parkinsonism because it blocked dopaminergic receptors in both limbic and extrapyramidal motor systems
Tardive dyskinesia (from chronic D2 receptor antagonism - D2 receptors become supersensitive to dopamine)

Front 12

How can tardive dyskinesia be managed and what can this result in?

Back 12

Usually irreversible, even after cessation of the drug. Can be controlled somewhat by increasing the dose of neuroleptic, but can develop severe Parkinsonian rigidity.

Front 13

Meth destruction of SN: MOA?

Back 13

Promotes increased rate of free radical production/oxidative stress.

Front 14

List the clinical symptoms of Parkinson's disease.

Back 14

Akinesia
Bradykinesia
Dyskinesia
Alterations in muscle tone
Impaired postural reflexes
Autonomic disturbances

Front 15

Akinesia: define.

Back 15

Disinclination to use an affected part of the body in a normal manner. Paucity of spontaneous movement and impairment in the initiaiton of normal movement.

Front 16

Akinesia: characteristics.

Back 16

Minimal facial expression, stare
Sit motionless for long periods
Don't swing arms
Normal reflex movements

Front 17

Bradykinesia: describe.

Back 17

Extreme slowness of movement or difficulty in initiating movement. Difficulty in stopping movement. Short shuffling steps.

Front 18

Dyskinesia: describe.

Back 18

Combination of rigidity and bradykinesia. Rhythmic tremor at rest.

Front 19

What makes dyskinesia of Parkinson's worse or btter?

Back 19

Better - diminished during intentional movement, disappears during sleep
Worse - emotional stress

Front 20

Describe muscle tone in Parkinson's.

Back 20

Muscles are firm and tense. Resist passive movement. In severe cases, individuals may be stiff and rigid - 'frozen.'

Front 21

How is muscle tone tested in Parkinson's?

Back 21

Tested by passively moving the patient's arm up and down at the elbow. The muscle resistance is overcome as a series of jerks - 'cogwheel' rigidity.

Front 22

Describe the impaired postural reflexes of Parkison's.

Back 22

Trunk is bent forwards. Stands with a stopp and arms flexed. If the patient's center of gravity is disturbed, the reflex to take a step back in order to balance is delayed.

Front 23

List the 3 autonomic disturbances of Parkinson's.

Back 23

Increased sebaceous gland secretion
Drooling
Coolness in the extremities

Front 24

Why are there autonomic disturbances with Parkinson's?

Back 24

In part, due to involvement of the globus pallidus which has connections to the hypothalamus.

Front 25

What medication can help with Parkinson's?

Back 25

L-dopa
Sinemet is a drug in this class (with a dopa-decarboxylase inhibitor)

Front 26

Sinemet: side effects?

Back 26

Hallucinations
Choreiform movements
Hypersexuality
Orthostatic hypotension

Front 27

When should Sinemet not be used and what do you use instead?

Back 27

Patients with a history of mental illness

Muscarinic cholinergic antagonists may help alleviated tremor and rigidity.

Front 28

Amantadine: MOA?

Back 28

Enhances dopamine release from neurons which have not yet degenerated

Front 29

Selegiline: MOA?

Back 29

Inhibits the metabolic breakdown of dopamine and may also have an independent protective effect slowing the degeneration of neurons.

Front 30

What type of transplantation has been tried for Parkinson's?

Back 30

Piece of adrenal medulla (fetal tissue - develops from neural crest cells) is transplated to the lateral ventricle. Limited transient success - Lewy bodies are present in the transplanted fetal tissue.

Front 31

What are 2 types of surgical intervention for Parkinson's?

Back 31

Pallidotomy - ablating GPi
Microelectrode implantation - stimulation of the subthalamic nucleus.

Front 32

Huntington's: inheritance? mutation?

Back 32

Autosomal dominant

Abnormal expansion of a CAG triplet repeat sequence on huntingtin gene on chromosome 4

Front 33

Huntington's: pathogenesis?

Back 33

Medium spiny neurons in the caudate and putamen that project to GPe degenerate. GPe neurons become abnormally active, reducing the excitatory output of the subthalamic nucleus to GPi and substantia nigra. Overall effect is to decrease inhibitory output to the thalamus.

Front 34

Huntington's: what other cells degenerate?

Back 34

Cortical pyramidal neurons - neocortex and allocortical areas

Front 35

Huntington's: hypothesis?

Back 35

Degenerative changes are the result of glutamate toxicity in the neostriatum.

Front 36

What are the 2 major types of symptoms in Huntington's?

Back 36

Chorea
Mental changes

Front 37

Chorea: describe.

Back 37

Motor disturbances characterized by non-rhythmic continuous involuntary movements, particularly of the distal extremities, face and tongue.
Advanced stages - never at rest.

Front 38

Mental changes of Huntington's: describe.

Back 38

Tries to hide movements over on. As the disease progresses, there is severe mental deterioration and usually marked paranoia. Highest rate of suicide for any neurological disorder.

Front 39

Sydenham's chorea: who gets it? prognosis?

Back 39

Occurs with a subacute onset in children with rheumatic fever

Usually transient with full recovery.

Front 40

What is Sydenham's chorea?

Back 40

Immunologic disorder in which the body produces antibodies to the streptococcal bacteria, which is similar to membrane of striatal neurons, so antibodies attack cells in the neostriatum and produce chorea.

Front 41

Ballismus: pathogenesis?

Back 41

Lesions of the subthalamic nucleus, decreasing the inhibitory outflow of extrapyramidal motor system nuclei leading to an abnormal discharge of UMNs.

Front 42

Balismus: symptoms?

Back 42

Flinging and ballistic movements, particularly involving the extremities. Movements disappear during sleep.
Violence of movements can keep the individual from being able to sleep, which leads to a rapid physical and mental deterioration.

Front 43

Ballismus: prognosis?

Back 43

Patients rarely survive more than 6-12 months

Front 44

What is dystonia?

Back 44

Disorders of the extrapyramidal motor system in which there may be an abnormal posturing of the trunk or extremity, caused by a maintained contraction of the muscles.

Front 45

What does dystonia result in?

Back 45

Hypertrophy of involved muscles. Very painful.

Front 46

Define torticollis.

Back 46

Focal dystonia involving cervical muscles.

Front 47

Define blepharospasm.

Back 47

Focal dystonia involving orbicularis oculi muscles.

Front 48

Define spasmodic dysphonia.

Back 48

Dystonia of the vocal apparatus

Front 49

Dystonia: etiology.

Back 49

Thought to involve the lentiform nucleus