10 - Movement Disorders Flashcards
What is a tremor?
Rhythmic, oscillating movement of body part; i.e. hand (but can be in the head)
What is ataxia?
- Clumsiness, instability, imbalance, or lack of coordination with voluntary movements
- Movements appear disjointed, unsteady gait, falls
What is dystonia?
- Involuntary muscle spasms
- Can be generalized or focal (hand - Writer’s cramp, neck - torticollis)
What is dyskinesia?
- Repetitive, purposeless, involuntary movements
- Grimacing, lip-smacking, rapid arm/leg movements
- Prolonged exposure to antipsychotics, neuroleptics
What is dysdiadochokinesia?
- Impaired ability of rapid alternating movements
What is chorea?
- Non-repetitive jerking movements of limbs, face or trunk
Describe the characteristics of an essential tremor
- “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
What are the two types of essential tremor?
- Kinetic
- Postural
Describe a kinetic essential tremor
Kinetic – tremor with movement of body part (writing, etc)
Describe a postural essential tremor
Postural – tremor when body part held against gravity
Describe the epidemiology of essential tremors
- 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
What are some possible risk factors for an essential tremor?
- Lead, beta-carboline alkaloids
- D3 dopamine receptor gene variant possibly associated with familial essential tremor
How do you diagnose an essential tremor?
- 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)
What things do you need to check if you are trying to figure out whether or not something is an essential tremor?
Check thyroid function, ceruloplasmin (to exclude Wilson’s disease especially in a patient
What is on your differential diagnosis when investigating for an essential tremor?
- Hyperthyroidism
- Parkinson’s Disease
- Enhanced physiologic tremor
- Wilson’s Disease (dysfunction of copper in the body - liver and eye)
- Medications
What types of medications can cause an essential tremor?
Amiodarone
- Beta agonists
- Lithium
- Theophylline
What are the treatment options for an essential tremor?
Treatment is targeted at symptom management
- Propranolol*
- Primodone
Describe propranolol as a treatment for essential tremor
- 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
Describe primidone as a treatment for essential tremor
- Unclear mechanism, likely GABA effect, 50-250 mg/day
- May be more beneficial in the setting of kinetic or intention tremors
Describe the disease condition described in Alice in Wonderland
- Todd’s syndrome
- Characterized by migraines predominantly in children that cause micropsia/macropsia (seeing small or large things)
Describe the pathophysiology of Parkinson’s disease
- 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
Describe the epidemiology of Parkinson’s disease
- 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
What are the possible risk factors associated with Parkinson’s disease?
- 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
What are the two classifications of PD?
- Primary
- Secondary
Describe primary PD
Idiopathic Parkinson’s Disease
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
What is MPTP?
- Precursor to MPP+, a neurotoxin that destroys dopaminergic receptors in substania nigra
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
What are the 4 cardinal signs and symptoms of PD?
- Resting tremor (4-6 Hz)
- Cogwheel rigidity
- Bradykinesia
- Postural instability
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
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
What are the three classes of treatment options for PD?
- Dopaminergic agents
- COMT inhibitors
- Antiviral agents
What dopamine agents will we talk about?
- Levadopa/Carbidopa
- Dopamine Agonists
- MAO-B Inhibitor
- Anticholinergic Agents
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 *****
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
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)
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
What are the two types of dopamine agonists?
- First generation
- Second generation
What is the first generation dopamine agonist?
Bromocriptine (Parlodel)
Do NOT need to memorize this ***
What are the second generation dopamine agonists?
- Ropinirole (Requip)
- Pramipexole (Mirapex)
- Rotigotine (Neupro)
Do NOT need to memorize this ***
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
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)
What are the two MAO-B inhibitors that you need to know?
B means Brain - they act in the brain
- Selegiline
- Rasaligine
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***
What are the two anticholinergics that you need to know?
Anticholinergics
- Trihexyphenidyl
- Benztropine
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
What are the COMT inhibitors that you need to know?
COMT inhibitors
- Entacapone
- Tolcapone
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
What is the antiviral agent that you need to know?
Amantadine
Sometimes used as an anti-viral, used to treat the flu
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
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
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
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
