10 - Movement Disorders Flashcards
1
Q
What is a tremor?
A
Rhythmic, oscillating movement of body part; i.e. hand (but can be in the head)
2
Q
What is ataxia?
A
- Clumsiness, instability, imbalance, or lack of coordination with voluntary movements
- Movements appear disjointed, unsteady gait, falls
3
Q
What is dystonia?
A
- Involuntary muscle spasms
- Can be generalized or focal (hand - Writer’s cramp, neck - torticollis)
4
Q
What is dyskinesia?
A
- Repetitive, purposeless, involuntary movements
- Grimacing, lip-smacking, rapid arm/leg movements
- Prolonged exposure to antipsychotics, neuroleptics
5
Q
What is dysdiadochokinesia?
A
- Impaired ability of rapid alternating movements
6
Q
What is chorea?
A
- Non-repetitive jerking movements of limbs, face or trunk
7
Q
Describe the characteristics of an essential tremor
A
- “Senile tremor”, “benign essential tremor”
- Most common tremor disorder
- Involuntary rhythmic, oscillatory movements (Alternating contraction of opposing muscles)
- There is NO related neurologic disease or medication ***
- It is just a tremor… It is essential
8
Q
What are the two types of essential tremor?
A
- Kinetic
- Postural
9
Q
Describe a kinetic essential tremor
A
Kinetic – tremor with movement of body part (writing, etc)
10
Q
Describe a postural essential tremor
A
Postural – tremor when body part held against gravity
11
Q
Describe the epidemiology of essential tremors
A
- Typical onset is in the mid 50s
- Average age at first clinic visit = 71 years old
- Slight male predominance (53%)
- Estimated prevalence of about 4% in adults
- Annual incidence of 0.6% for age > 65 years
12
Q
What are some possible risk factors for an essential tremor?
A
- Lead, beta-carboline alkaloids
- D3 dopamine receptor gene variant possibly associated with familial essential tremor
13
Q
How do you diagnose an essential tremor?
A
- Based on history and physical exam
- Tremor usually 4-12 Hz (cycles/second)
- Usually asymmetric, hands > lower extremities
- Tremor of head may sole symptom or associated with extremity tremor
- Need to rule out other disorders that may mimic essential tremor *** (main point)
14
Q
What things do you need to check if you are trying to figure out whether or not something is an essential tremor?
A
Check thyroid function, ceruloplasmin (to exclude Wilson’s disease especially in a patient
15
Q
What is on your differential diagnosis when investigating for an essential tremor?
A
- Hyperthyroidism
- Parkinson’s Disease
- Enhanced physiologic tremor
- Wilson’s Disease (dysfunction of copper in the body - liver and eye)
- Medications
16
Q
What types of medications can cause an essential tremor?
A
Amiodarone
- Beta agonists
- Lithium
- Theophylline
17
Q
What are the treatment options for an essential tremor?
A
Treatment is targeted at symptom management
- Propranolol*
- Primodone
18
Q
Describe propranolol as a treatment for essential tremor
A
- Beta blocker, non-selective
- Long or short acting, 60-800 mg/dy for short acting
- Improved clinical symptoms and reported severity
FIRST LINE ***
Give this unless they cannot tolerate this
19
Q
Describe primidone as a treatment for essential tremor
A
- Unclear mechanism, likely GABA effect, 50-250 mg/day
- May be more beneficial in the setting of kinetic or intention tremors
20
Q
Describe the disease condition described in Alice in Wonderland
A
- Todd’s syndrome
- Characterized by migraines predominantly in children that cause micropsia/macropsia (seeing small or large things)
21
Q
Describe the pathophysiology of Parkinson’s disease
A
- Loss of dopaminergic neurons in Substania Nigra
- Neurons die and degenerate
- Imbalance in DA : Ach in striatum = improper signalling pathway for cortical motor commands
- Possibly related to alpha-synuclein; defective degradation leads to increased alpha-synuclein in nigrostriatal neurons
We currently believe that this build up of alpha-synuclein can cause the symptoms of Parkinson’s
22
Q
Describe the epidemiology of Parkinson’s disease
A
- Slight male predominance
- Prevalence increases with age
- 41 per 100,000 in age 40-49 years old
- 1,903 per 100,000 in age >80 years old
- Gets a lot more prevalent as you get older
23
Q
What are the possible risk factors associated with Parkinson’s disease?
A
- Pesticides
- Head injury
- Family history
- History of poliomyelitis (polio)
- Genetic predisposition – 9 genes, several loci
- Approximately 10-15% of PD patients have this genetic predisposition
- PARK2 gene in 8.6% of early onset PD patients have this predisposition
None of which have been proven very well
24
Q
What are the two classifications of PD?
A
- Primary
- Secondary
25
Describe primary PD
Idiopathic Parkinson’s Disease
26
Describe secondary PD
History of another condition which has contributed to the development of PD
- Infectious (viral encephalitis)
- Atheroslcerotic
- Drug induced
- Toxic agents (CO, manganese)
- Head trauma, tumors
27
What is MPTP?
- Precursor to MPP+, a neurotoxin that destroys dopaminergic receptors in substania nigra
28
Describe the unfortunate 1976 discovery of MPTP
- Graduate chemistry student who synthesized MPPP (opioid drug, similar to morphine)
- Injected into himself, along with MPTP impurity
- Rapidly developed Parkinson’s like symptoms
- He was treated with levodopa
- Died almost 2 years later from cocaine overdose
- Autopsy revealed destruction of dopaminergic neurons in SN
This has given us the idea that these patients may have some sort of a neurotoxin affecting them
29
What are the 4 cardinal signs and symptoms of PD?
******
- Resting tremor (4-6 Hz)
- Cogwheel rigidity
- Bradykinesia
- Postural instability
30
What are some other early motor findings associated with PD?
May occur before the big 4 cardinal signs will begin
- Micrographia, decreaesd dexterity
- Intermittent unilateral resting tremor
- Hypophonia – softening of voice
- Stooping posture
- Masked face (look like no expression on their face - sad)
- Shorter steps with unsteady gait
31
How do you treat PD?
- Treatment is targeted to symptom management
- Treat the most bothersome symptoms first
- Initiate treatment when patient begins having functional disability
- Consider limiting levadopa therapy in younger patients or those with expected long-term treatment
If someone has a symptom that is not really bothering someone, you don't have to treat them because the side effects are significant
32
What are the three classes of treatment options for PD?
- Dopaminergic agents
- COMT inhibitors
- Antiviral agents
33
What dopamine agents will we talk about?
- Levadopa/Carbidopa
- Dopamine Agonists
- MAO-B Inhibitor
- Anticholinergic Agents
34
Describe the levodopa/carbidopa combo drug
*****
Levodopa – crosses the BBB to act as dopamine precursor
Carbidopa – inhibits the peripheral degradation of levodopa by inhibiting dopamine decarboxylation
Combination medication = Sinemet *****
35
What are the advantages of levodopa/carbidopa therapy?
MOST EFFECTIVE TREATMENT FOR PD ***
- Most efficacious PD medication
- Nearly all patients respond
- Symptomatic Improvement
- Possible decreased mortality
36
What are the disadvantages of levodopa/carbidopa therapy?
- Does not stop progression
- Motor fluctuations (wears off throughout the day - "on-off" phenomenon)
- Most patients develop motor complications because there is overstimulation (Dyskinesia
Choreoathetotic, Dystonic)
37
Describe the details of levodopa/carbidopa complications
- Motor fluctuations dependent on duration and dose
- Majority of patients will have issues >15 yrs of treatment
- Difficult management of symptoms
- Does not stop: freezing, instability, autonomic dysfunction
- Levodopa is absorbed by the gut via amino acid transporters
- High protein diets can effect absorption
38
What are the two types of dopamine agonists?
- First generation
| - Second generation
39
What is the first generation dopamine agonist?
Bromocriptine (Parlodel)
Do NOT need to memorize this ***
40
What are the second generation dopamine agonists?
- Ropinirole (Requip)
- Pramipexole (Mirapex)
- Rotigotine (Neupro)
Do NOT need to memorize this ***
41
What are the advantages of using these dopamine agonists?
- Direct dopamine stimulation
- Good monotherapy in early PD
- No interference with dietary protein or amino acids
- Longer duration
- Less motor complications
- Possible protective effect
42
What are the disadvantages of dopamine agonists?
- Not a long term monotherapy
- Still some motor complications
- Does not stop progression
- Does not treat all aspects (freezing, instability, autonomic dysfunction)
43
What are the two MAO-B inhibitors that you need to know?
****
B means Brain - they act in the brain
- Selegiline
- Rasaligine
44
Describe the use of MAO-B inhibitors in PD patients
- Monoamine oxidase inhibitors
- Inhibit dopamine metabolism in the brain
- May be initial treatment for patients with minimal functional disability
- Some may have neuroprotective effects (rasaligine)
If they don't have any dopamine being made (later on in the disease), it will not e effective - only works early on***
45
What are the two anticholinergics that you need to know?
****
Anticholinergics
- Trihexyphenidyl
- Benztropine
46
Describe the use of anticholinergics in PD patients
- When dopamine decreases, cholinergic effects predominate
- Treatment is intended to decrease cholinergic activity and balance the decreased dopamine effect
- Predominantly used for tremor
- ASE: dry mouth, urinary retention, altered mental status
47
What are the COMT inhibitors that you need to know?
****
COMT inhibitors
- Entacapone
- Tolcapone
48
Describe the use of COMT inhibitors in the treatment of PD patients
****
- Increases duration of levodopa by inhibiting metabolism of levodopa by COMT
- Adjunctive treatment with levodopa/carbidopa to decrease “wearing off” effect
- NOT MONOTHERAPY ***
- Monitor LFTs with Tolcapone due to possible hepatotoxicity
49
What is the antiviral agent that you need to know?
****
Amantadine
Sometimes used as an anti-viral, used to treat the flu
50
Describe the use of antiviral agents used to treat PD patients
- Discovered to have antiparkinson activity
- Unknown mechanism of action
- Possibly useful early on, or as adjunct to levodopa therapy
51
What is the use of surgical treatment of PD patients?
- Intended for disabling PD despite optimal medical management
- Poor candidates include those with high operative risk or significant cognitive decline
52
What are the surgical options for treating PD patients?
- Ablation – thalamotomy, pallidotomy
- Deep Brain Stimulation – placed with stereotactic approach with MRI or CT
- Restorative – fetal human/porcine nigral transplant
53
Here are the things you need to know...
- Big things – how do you diagnose essential tremor
- How do you treat essential tremor or PD
- What are the things you look for in patients with a tremor
- Don’t need to know any dosing information
- Do need to know which medications to use, when to use them and whether or not they are indicated
