Parkinsonism and Parkinson's Disease Flashcards
What can be defined as any combination of tremor, rigidity, bradykinesia, and progressive postural instability?
Parkinsonism
What is the gender and ethnic distribution among patients with Parkinsonism?
Occurs in all ethnic groups, with an approximately equal sex distribution
Idipathic Parkinson disease begins most often between the ages of __-__.
45-65
Parkinsonism may result form mutation of hat 5 genes?
- Alpha-synuclein
- Parkin
- LRRK2
- DJ1
- PINK1
Mutations in what gene account for some cases of sporadic Parkinson disease?
LRRK2
What environmental factors may lead to Parkinsonism?
- Exposure to certain toxins (maganese dust, carbon disulfide)
- Severe cases of carbon monoxide poisoning
Reversible parkinsonism is sometimes seen in what type of patients?
patients receiving neuroleptic drugs, reserpine, or metoclopramide
What is the main cause of idiopathic parkinsonism?
Dopamine depletion which leads to an imbalance of dopamine and acetylcholine
Because dopamine depletion is often the cause what is the focus of treatment?
Blocking the effect of acetylcholine
Serum urate levels are a prognostic factor in that the rate of progression declines as the urate level _____.
increases
What are 5 risk factors for developing Parkinson’s disease?
- Age
- Family history
- Male sex
- Ongoing herbicide/pesticide exposure
- Significant prior head trauma
What are 4 protective factors against Parkinson’s disease?
- previous ibuprofen use
- smoking
- caffeine
- coffee
A disruption in the direct pathway leads to what?
Akinesia/bradykinesia
A disruption in the indirect pathway leads to what?
Resting tremor
What are the 4 cardinal signs of parkinsonism?
- Tremor
- Rigidity
- Bradykinesia
- Postural instability
Describe tremors associated with parkinsonism
- they can occur in all limbs
- a tremor of 4-6 cycles is conspicuous at rest
What increases tremors?
emotional stress
What produces less severe tremors?
voluntary activities
What is responsible for the characteristically flexes posture?
rigidity
Define rigidity
an increase in resistance to passive movement
What is the most disabling symptom of parkinsonism?
bradykinesia
Define bradykinesia
A slowness in voluntary movement and a reduction of automatic movements such as swing of the arms while walking
What are 10 other characteristics of parkinsonism?
- relatively immobile face
- decreased or infrequent blinking
- lack of facial expression
- saliva drooling from the mouth
- seborrhea of the scalp and face
- mild blepharoclonus
- tremor around the mouth and lips
- tremor around the mouth and lips
- impaired swallowing
- soft and poorly modulated voice
Do people with parkinsonism exhibit with muscle weakness or decreased DTRs?
No
How is parkinsonism diagnosed?
If bradykinesia is present with either a tremor or rigidity
What 2 common diagnoses may be mistaken for mild parkinsonism?
- old age (hypokinesia and resting tremor)
- depression (absent facial expressions)
What is the major difference between an essential tremor and parkinsonism?
Essential tremors are typically more of an action tremor than resting type tremor
What movements do essential tremors affect?
head movements
What type of tremors are associated with parkinsonism?
tremors of the jaw or lips
What are 6 differential diagnoses to Parkinson’s disease?
- Wilson disease
- Huntington disease
- multiple system atrophy
- progressive supranuclear palsy
- Jakob-Creutzfeldt disease
- corticobasilar degeneration
- drug induced parkinsonism
How can Wilson’s disease be distinguished from PD?
- early age onset
- Kayser-Fleischer rings (iris)
- chronic hepatitis
- increased copper concentrations in the tissues
How can Huntington’s disease be distinguished from PD?
- early age onset
- chorea like movements
- athetosis
How can multisystem atrophy be distinguished from PD?
- autonomic insufficiency (postural hypotension, anhidrosis, disturbances of sphincter control, ED)
- pyramidal deficits
- lower motor signs
- cerebellar dysfunction
How can progressive supranuclear palsy be distinguished from PD?
- eye movements (downward gaze)
- postural instability (ataxia)
- axial dystonia
- pseudobulbar palsy (dysarthria/dysphagia)
- pseudo-emotional liability
What is Jakob-Creutzfeldt disease due to?
infection
How can Jakob-Creutzfeldt disease be distinguished from PD?
- Dementia: memory loss, hallucination, psychosis
- Myoclonic jerking
- Ataxia
- Pyramidal signs
- MRI and electroencephalograph findings
How can corticobasal degeneration be distinguished from PD?
- absence of tremor
- lack of L-dopa response
What are the distinctive features of corticobasal degeneration?
- ideomotor apraxia
- alien limb phenomenon
- aphasia
- loss of cortical sensory function
How can drug induced parkinsonism be distinguished from PD?
it is reversible
What patient population is vulnerable to drug induce parkinsonism?
AIDS
Symptoms of drug induced parkinsonism should subside - weeks after medication
4-6
Because there is no cure for PD, treatment is focused on what?
controlling the symptoms associated with PD
What are the 7 medical measures taken to treat PD?
- amantadine
- anticholinergic drugs
- levodopa
- dopamine agonists
- selective monoamine oxidase inhibitors
- COMT inhibitors
- atypical antipsychotics
What type of patients may be helped with amantadine?
those with mild symptoms but no disability
The side effects of amantadine are uncommon with the typical dosage of ___mg given twice a day orally
100
What are anticholinergic drugs beneficial in relieving?
tremors and rigidity (no so much bradykinesia)
What are 5 examples of anticholinergic drugs?
Benzotropine mesylate (Cogentin)
- Biperiden (Akineton)
- Orphenadrine (Disipal, Norflex)
- Procyclidine (Kemadrin)
- Trihexyphenidyl (Artane)
What is the most effective drug for treating PD?
Levodopa (L-DOPA)
How does L-dopa function to treat PD?
It is converted into dopamine in the body which increases overall dopamine levels in the brain
What symptoms of PD are improved through the use of L-dopa?
All major aspects of parkinsonism
However, it does not decrease progression of the disease
The __-__ phenomenon is a late complication of L-dopa. Describe this phenomenon
on-off
Abrupt but transient fluctuations in the severity of parkinsonism occur unpredictably but frequently during the day
What is the “off” period of the on-off phenomenon marked by?
bradykinesia
What is the “on” period of the on-off phenomenon marked by?
increased mobility
How does L-dopa cross the blood brain barrier?
An enzyme (DDC) converts L-dopa into dopamine which can then cross the barrier
What DDC inhibitor is oftentimes given in combination with L-dopa in order to reduce the associated side effects?
Carbidopa
Does the combination of Carbidopa and L-dopa prevent the “on-off” phenomenon?
No
What medication provides an already prepared combination of carbidopa and L-dopa in either a 1:10 or 1:4 ratio?
Sinemet
Precautions to taking L-dopa should be considered in what type of patients?
Those with active peptic ulcers or malignant melanomas
How do dopamine agonists help in treating PD?
They act directly on dopamine receptors, and their use in parkinsonism is associated with a lower incidence of the response fluctuations and dyskinesias that occur with long-term L-dopa therapy
When are dopamine agonists best administered?
before L-dopa or with a low dose of Sinemet
What are 2 dopamine agents that are effective at the early and advanced stages of Parkinson disease?
- Pramipexole
- Ropinirole
Pramipexole – most individuals require __-__ mg 3x daily taken orally
0.5 - 1.5
Ropinirole – most individuals require - mg 3x daily
2 to 8
What are 2 examples of selective monoamine oxidase inhibitors (MAOIs)?
- Rasagiline
- Selegiline
How do MAOIs function in treating PD?
They inhibiting the metabolic breakdown of dopamine which improves the fluctuations or declining response to L-dopa
Why should high tyramine foods be avoided while taking MAOIs?
They may cause hypertension
What foods are high in tyramine?
- cheese
- cured meats (pepperoni, summer sausage, salami)
What are 2 examples of Catecholamine-O-Methyltransferase inhibitors (COMT inhibitors)?
- Tolcapone
- Entacapone
How do COMT inhibitors function in treating PD?
They reduce the metabolism of levadopa to 3-O-methyldopa which thereby alters the plasma pharmacokinetics of L-dopa, leading to more sustained plasma levels and more constant dopaminergic stimulation of the brain
What does treatment with COMT inhibitors do?
Reduces the response fluctuations and increases period of responsiveness to levodopa. However, it does not delay levodopa-induced dyskinesia
Which COMT inhibitor is used more frequently and why?
Entacapone, because Tolcapone may cause liver toxicity
What drug is the commercial preparation of levodopa combined with carbidopa and entracapone?
Stalevo
What are confusion and psychotic symptoms associated with dopaminergic therapy treated with?
atypical antipsychotics agents
What are 4 examples of atypical antipsychotics used?
- clozapine (most effective)
- olanzapine
- quetiapine
- risperidone
What types of therapy may benefit patients with parkinsonism?
- PT
- OT
- Speech
What 2 surgical procedures can be used for patients who become unresponsive to medical treatment or have intolerable side effects?
- Thalamotomy: destruction of part of the thalamus with a liquid nitrogen frozen probe
- Pallidotomy: destruction of the globus pallidus on one side of the body
Describe what a deep brain stimulator does
Provides high frequency electrical stimulation of the subthalamic nuclei or globus pallidus
