Parkinson's Disease & Movement Disorders (Exam V)

Question 1

What symptom is the hallmark of Parkinson’s disease?

What are the TRAP symptoms with Parkinson’s disease? essay question

Answer 1

Tremor at rest (rhythmic movement around a joint)

Tremor
Rigidity
Akinesia - loss of ability to move muscle voluntarily
Postural instability.

Question 2

What is Chorea?

What is Ballismus?

Answer 2

• Muscle jerking in various areas
• Violent abnormal movements (extreme version of chorea)

Question 3

What is Athetosis?

Is this indicative of Parkinson’s disease?

Answer 3

• Slow, writhing movement
• Not typical of Parkinson’s

Question 4

What is Dystonia?

What are Tics?

Answer 4

• Abnormal posture w/ no movement, jointed locked, usually seen with cerebral palsy.
• Single, repetitive movements (especially facial)

Question 5

What collection of neurons regulates motor activities?

Answer 5

• Basal Ganglia/Nuclei

Question 6

Communication from the motor cortex to the thalamus goes through the _____ ______.

Answer 6

Basal Ganglia

Question 7

What are two movement disorders related to basal ganglia dysfunction?

Answer 7

Parkinsons: Destruction of Dopaminergic Neurons
-Need Dopamine (L-Dopa)

Huntingtons: Destruction of GABAnergic Neurons
-Need to decrease dopamine (Tetrabenazine)

Question 8

What is damaged in Parkinson’s.

Answer 8

The pars compacta in the substanstia nigra is damaged. No dopamine release to provide a negative feedback to the thalamus, this will lead to movement disorders.

Question 9

What is the pathogenesis of Parkinsonism?

Answer 9

Decrease in Dopamine Levels in the Nigro-striatal pathway

Question 10

What are protective environment factors for Parkinsonism?

What are harmful environment factors for Parkinsonism?

Answer 10

Protective factors: Cigarette smoking, Coffee, Anti-inflammatories, Uric Acid

Harmful: Lead, Manganese Exposure, Vit D Deficiency

Question 11

What genetic component is often present in Parkinson’s patients?

What is the result of this mutation?

Answer 11

• SNCA - α-Synuclein (NT release)

Misfolding produces Lewey Bodies

Question 12

What drug is given as firstline treatment for Parkinson’s?
Why this drug?

Answer 12

• Levo-dopa (dopamine precursor)
• Able to cross BBB unlike dopamine

Question 13

What are the treatments for Parkinson’s? Essay Question

Answer 13

1. Exercise/ Physical Therapy
2. Levo-Dopa- restore dopamine levels
   -Improve uptake with carbidopa- inhibits dopa decarboxylase
   -Improve uptake with COMT inhibitors (tolcapone)
   -Decrease toxicity (hallucinations) with pimavanserin (Nuplazid)
3. CNS antimuscarinics- to reduce tremors
4. Dopamine receptor agonist
5. MAO-B Inhibitors (Selegeline)

Question 14

What should be avoided when one has Parkinson’s Disease?

Answer 14

Dopamine receptor antagonist (antipsychotics, D2 antagonist, Haldol)

Question 15

How much of L-Dopa crosses the BBB?
Can this be increased? With what? How much?

Answer 15

• 1-3%
• With Carbidopa (10% uptake of Levo-dopa)

Question 16

How does carbadopa work?

Answer 16

• Inhibits Dopa-Decarboxylase from forming dopamine peripherally (thus saving Levo-dopa for the CNS)

Question 17

Is Levo-dopa a treatment or a cure for Parkinson’s?

Answer 17

• Treatment, effective for a period of time before more neurons degrade.
• Over the next 10-15 years this will be less and less effective

Question 18

What adverse effects can be seen from levodopa?

How will you decrease the toxicity of levodopa?

Answer 18

• Delusions and Hallucinations
  This is worse with carbidopa

Primavanserin (Nuplazid)

Question 19

What is the On-Off Phenomenon with Levo-dopa?

What can you take to decrease these symptoms?

Are drug holidays recommended?

Answer 19

Associated with long-term use (10 years+). Increased mobility followed by marked akinesia, very frustrating for patients.

Apomorphine

Drug holidays for 3 to 21 are not recommended, but patient’s will still self demedicate.

Question 20

What drug interactions exist for Levodopa?

What contraindications exist for Levodopa?

Answer 20

Vitamin B6 & MAOI’s

• Psychosis (↑ dopamine signalling)
• Glaucoma
• Melanoma (L-dopa feeds these tumors)

Question 21

How is L-Dopa broken down peripherally?

What drug inhibits this?

Answer 21

COMT Enzyme will break down L-DOPA to 3-OMD
DOPA decarboxylase will break down L-DOPA to Dopamine (but its in the periphery, we need it in the brain)

Entacapone & Tolcapone will inhibit COMT Enzyme
Carbidopa will inhibit DOPA Decarboxylase

• This will ensure there are more L-DOPAs in the periphery to cross the BBB.

Question 22

Once L-DOPA crosses the BBB, DOPA decarboxylase converts the compound to Dopamine. What breaks down dopamine in the brain?

What drug can prevent the breakdown of Dopamine in the CNS by inhibiting MAOB?

What drug can prevent the breakdown of Dopamine by inhibiting the COMT enzyme?

Answer 22

Monamine Oxidase B and COMT will break down Dopamine in the brain.

Selegiline, Rasagiline- these are given with L-DOPA

Tolcapone

Question 23

What is the most common movement disorder?

What is essential tremors indicative of?

What is the treatment?

Answer 23

Essential tremor (β1 receptor dysfunction) tremor with movement

Essential tremors are indicative of brain lesions or EtOH, not Parkinsons

• βblockers

Question 24

What is benign hereditary chorea?

What is the treatment?

Answer 24

Chorea in childhood with no progression and no dementia.
Clear genetic predisposition: autosomal dominant 50% chance of passing this on to their offspring.

Tetrabenazine (↓ Dopamine)

Question 25

What is Tardive Dyskinesia? What is the most common cause?

Answer 25

Repetitive, involuntary movements. Anti-psychotic drugs, other drugs that will cause TD will include Levodopa, Phenytoin, other seizure drugs.

Question 26

What is the most common & severe muscular dystrophy disorder? Who and how is it inherited?

Answer 26

- Duchenne's Muscular Dystrophy (most severe) - X-linked recessive (males) - passed by mother to sons

Question 27

What sign is seen with children who have Duchenne's MD? Where will muscle wasting occur in the body? What is the life expectancy of someone with Duchenne Muscular Dystrophy? Treatment?

Answer 27

Gower's Sign - using hands to pushing on legs to stand. Major Skeletal Muscle Some Cardiac Muscle Smooth Muscles They don't typically survive beyond their 20s. Corticosteroids Beta-2 agonist (muscle strength) - by increasing blood flow in the skeletal muscle. Braces

Question 28

What characterizes Cerebral Palsy? What is the usual cause? Symptoms? Treatment?

Answer 28

**Non-progressive** motor disorder of the CNS. Birth Trauma, Hemorrhage, Anoxia Wide spectrum of signs and symptoms can be hyper or hypotonia. Surgery, Intrathecal Baclofen pump to the spinal column (muscle relaxant) to treat spasticity.

Question 29

When does Huntington's disease normally occur? Is this disease autosomal dominant or recessive? Symptoms of Huntington disease? When does death occur?

Answer 29

Age 30 - 40 Autosomal Dominant Disorder- Chromosome #4 Progressive loss of muscle control Chorea Dementia Death 15-20 years after onset of symptoms. No cure.

Question 30

What characterizes the pathophysiology of Huntington's disease?

Answer 30

- GABA reduced in the basal ganglia - Reduction in ChAT (Choline Acetyltranferase) - Excess Dopamine

Question 31

What treatments are there for Huntington's disease?

Answer 31

- Tetrabenazine = ↓ excess dopamine - Dopamine Receptor blockers (ex. Haldol) - Genetic Counseling, Speech Therapy, PT/OT

Question 32

What is ALS/ Lou Gehrig's Disease? When does onset occur? When does death occur?

Answer 32

A rare progressive neurological disorder characterized by loss of motor neurons 40-60 years old, more common in men. 2-6 years after diagnosis

Question 33

What are the treatments for Lou Gehrig's disease?

Answer 33

- Riluzole - Na⁺ channel blocker (specific for damaged neurons) - Edaravone - antioxidant.

Question 34

What are some theories involving Alzheimer's Disease? What two anatomical changes are seen in Alzheimer’s disease?

Answer 34

Genetic predilection/Nonhereditary Head Injury Dysregulated Lipids Low Estrogen 1. Neurofibrillary tangles inside the neuron (Tau proteins) 2. Amyloid/Senile plaques outside the neuron

Question 35

What palliative treatments are available for Alzheimer's disease? Clinical Manifestations of Alzheimer Disease How is diagnosis made?

Answer 35

CNS AChE inhibitors (Tacrine: ↑ACh at synapse) NMDAr Antagonist (Memantine)- slow the effects of dementia. Forgetfulness, emotional disturbance, disorientation, confusion, lack of concentration, decline in abstraction, problem solving, and judgement. Insidious onset. Dx made by ruling out other causes of dementia.

Question 36

What are the treatment's for restless leg syndrome?

Answer 36

- Dopamine agonists - Opiates (Clonazepam) - Gabapentin - Benzodiazepines