Parkinson's Disease Flashcards
Differentiate between Parkinsonism and Parkinson’s Disease
Parkinsonism
- a neurologic syndrome or group of symptoms, spcifically motor symptoms
- can be atypical parkinsonsim (lewey body, supranuclear, corticobasal), drug-induced or vascular as the cause
Parkinson’s Disease
- a neurodegenerative disorder of the CNS as a result of idiopathic loss of dopamenergic neruons
- also can be called idopathic parkinsonism
- genetic in nature or idopathic
so what is Parkinson’s Disease by Definition
predispositions?
- a neruodegerative disorder that can be seen as a “shaking palsy”
- idopathic in nature but there are some environmental and genetic predispositions
- AGE IS THE MOST POTENT RISK FACTOR FOR PD: 2nd most common age related neurodegenerative disorder
- risk doubles each decade after 50
Predispositions
- Genetics: GBA & LRRK2 & others
- Environment: pesticide use, rural areas, well water, and MPTP neurotoxin use (can be seen in street drugs
- can come on after a physcial trauma: like a fall or broken arm
Etiology of PD
normal role of dopamine in the body
a disease of the basal ganglia
BG strucutres
- caudate
- putamen
- nucleus accumbens (reward pathway)
- GP interna and externa
- subthalmatic nucl.
- substantia nigra these is where we see the dopamine depleteion
Dopamine: what does it do
- a monoamine neurotransmitter
- functions in : movement, memory, behavior, attention and cognition, sleep, arousal and mood
- naturally: its broken down my MAO, COMT, ALDH
specifically motor function: relies on the dopamine to project from the substantia nigra to teh dorsal struatum: when this is lost we see the results/symptoms of PD
Pathophysiology of PD
a decreased level of dopamine
- there is cellular death in teh substantia nigra
- the lackof dopamine in the SN leads to motor dysfunction
pathologically see: Lewy bodies on autopsy
- these lewy bodies are intracellular inclusions (aka protein buildups) of the alpha synuclein protein that gets built up and forms these lewy bodies, less dopamine produced and decrease motorfunction
Symptoms and cardinal features of parkinson’s disease
Cardinal Symptoms of PD: motor dysfunctions
- Bradykinesia: slowed movements this is NEEDED to make the diagnosis of parkinson’s disease
- Resting Tremor
- Muscular Rigidity: cogwheel or leadpipe rigitiy on passive ROM
- Postural instability: not caused by other visual, vestibular, cerebellar or proprioceptive dysfunction
Explain the details of Bradykinesia
how to test your pateints
Brady = slow kinesia = movements
because the lack of dopamine is a gradual progression/loss - the progression of symptoms will also be gradual
- lack of spontaneous movements
- loss of iADLS and ADLS
- freezing of gait & movements
Ways to Test for Bradykinesia
- UE: finger tapping, hand opening, pronation&supanation
- LE: toe tapping and heel stomping
Tremor of PD patients
- characteristics of it
- how to test
Tremor of PD
- a resting tremor; described as “pill rolling” sititng with hands up
- can be bilateral, but most pt. have one side worse than the other
- frequency of the tremor: 3-5 Hz frequency
most pts. will have the tremor at the time of diagnosis
Tremor Characteristics
- accentuated by mental concetration: when you tell them to focsu on something in their head, it will come out
- upon postural changes; it may go away but will reappear (differ from procedural tremor)
How to test
- notice it during exam
- have pt. put arms out front and hold still
- make them thing about something (mental concentration)
- see the tremor reappear
Rigidity of PD pts.
how to test
Rigidity
- of the neck, shoulders, wrists and legs
Signs
- shown by decreased ROM
- decreased arm’s swinging during gait
- Cogwheel with passive ROM testing: ratchet-like jerks on exam when trying to passive ROM them
Postural Instability of PD pts.
how to test
Postural Instability
presents
- inability to be balanced when standing
- difficult ot make turns; take many little steps tp turn
- can increase fall risk
Test
- Retropulsion Test: stand behind them and pull their trunk backwards, they should take 1-2 steps to stabilize themselves; but a complete loss of balance = postive test
- or can tell their instability of gait upon exam seeing them enter the room
Specific aspects of your Pts. gait that may make you think they have PD
- decreased arm swing
- shuffling gati
- stopped posture
- freezing of gait (doorways and upon turning)
- reemergence of tremor
- en-block turning (little baby steps)
- festation: during walking their steps are small and shuffle-like
Secondary Symptoms of PD
- hyposomia
- REM behavior disorder: reported by bed partner that they’re acting out their dreams
- constipation: because they’re moving less
- hypophonia: soft speech
- micrographia: small handwriting
- mypomimia: loss of facial expression “marked facies”
- increase saliva
- mood changes
- cognitive impariment
- fatigue
- dysphagis (becuase of muscles)
- difficulty with dexterity and turning in bed
Diagnosis of PD
the diagnosis of PD can be made clinically, with the cardianl symptoms present
- first; you need to rule out parkinsonism as a result of other etiologies (like drug-induced)
- a trial of Levodopa with efficacy can help
DAT scan to confirm the diagosis (dopamine transporter scan - DA SPECT)
- a NEGATIVE scan does NOT rule out the diagnosis
- not necessary to do but can be definitive in diagnosis
- results: “comma shape” = normal a “period shape” indicates a lack of DA in the brain
how to differentitae between PD and an essential tremor
Parkinson’s Disease
- a RESTING tremor
- can be bilateral; but one side will be worse than the other
Essential Tremor
- action tremr: present when they are moving
- present in the arms, the head and the voice
- the ET will improve with alcohol use
Nonpharmacologic Treatment of PD
Exercise!: the only way to SLOW progression of the disease is through exercise
- 30 minutes at least 4x/week
- variety in exercise will produce best results
Physiacal Therapy
- ambulation & balance training
- freezing of the gait
- abulation device for safer moving
Occupational Thearpy
- gait, bathroom saftey and device use
Speech Therapy
- to increase voice; loud therapy
- cognitive therapy
When do you start medication in your PD pts?
what med do you start first
medication are used to help with the symptoms of the disease; they are not able to curve or even stop neruoprogression
when to start? use the pt. ability and level of functioning to gage when medications should be introduced
FIRST LINE MEDICATION: Levodopa: a dopamine replacement medication (the precursor to dopamine)
Second-line: Dopamine agonists: but these can cause non-motor side effects (avoid in pts. > 70)
Levodopa/Carbidopa
- how does it work
- what does the addition of carbidopa do
- how to dose (generally)
Levodopa: a dopamine precursor: converted to DA once in the CNS and in the periphery
Carbidopa: an add on within the formulation; help to reduce the peripheral conversion of DA (becuase you really only need to DA to be converted within the CNS)
- also helps to decrease the N/V and GI side effects that levodopa has
- does not cross the BBB
Dosing
- strat very slow, with like 1/2 tablet and slowly increase to 1 tablet 3x daily
- titrat up for optimal symptom control
Side Effects of CD/LD
Motor Complications: Response Duration
- nausea/abd. cramping : this is where the addition of more carbidopa can be helpful to decrease these effects
- Dyskinenas: wiggling movements as a result of too much DA in the body (at peak or during wear off)
- Orthostatic Hypotention
- Hallucinations (visutal or auditory)
- “On-Off” phenomenon (fluctuation in thier motor symptoms; which is why its dosed multiple times a day
- Dystonia: foot or cervical; abnormal posturing
Motor Complications with CD/LD
- the levodopa response duration shortens with increase use of the medication & with teh progression of the PD
- with progression of parkinson’s disease: the therapeudic window of levodopa shortens, making it harder to achieve motor symptom control without getting additional dyskinesia SE along with the medication
- a pulsitile stimulation of declining number of receptors lead to hypersensitivity of the receptor to the medication
ways in which medication dosing can help try to combat the motor complications and decrease effectiveness of CD/LP with progressive PD
Immediate release and controlled release formulations exists
- controlled release: good for those who need it overnight to wake up without crazy intesne symptoms
a combo: of IR/CR = help to improve ON time without dyskinesia & motor function
- enteral levodopa and oral inhalation exist
Dopamine Agonists: second line medication for PD
Dopamine Agonists: directly increase the amount of dopamine wihtin the body
Ropinirole
Pramipexole
when to start
- can be introduced when levodopa response is variable
- starting thease earlier in younger pts. : can help delay the need to start levodopa as soon
these have less nausea and GI side effects
SE
- IMPLUSE CONTROL DISORDER: gambling, risky behavior: failure to resistn tempation or urge (hypersexual, eating, gambling, etc.) because DA is in teh reward pathway = reduce or d/c med, councel and education via CBT
- sudden sleep attacks
- othrostatic dizzy
MAO-B INhibitors for PD
when to use
MOA-B Inhibitors: MAO breaks down DA: so if you inhibit their ability to breakdown –> you get increase DA in the body
Selegiline & Rasagiline
- well-tolerated, improve ON time, possible neuroprtective
SIDE EFFECTS = are huge and not great
- lots of D-D interactions: tyramines, SSRI/SNRI, meperidine, dextamethorophan
- possibly exacerbates dyskinesia and orthostatic hypotensions
COMT INhibitors for PD
- what are they
- how do they work
- side effects
COMT INhibitors
Entacapone : inhibits peripheral conversion of levodopa: therefore helps with ON time of levodopa activity
must be taken with levodopa, its only role is to help the action of levodopa
Side Effects
- diarrhea
- orange urine
- dysnkinesia
- hallucinations
- low BP
Amantadine for PD
how does it work
side effects
Amatadine; glutamte antagonist
- non-competitive antagonist of NMDA glutamatergic receptors –> thought to help increase levels of DA in the brain (dopamenergic)
Side EffeectS: mild anticholenergic effects
- dry mouth, urinary retention
- constipation
- hallucinations
- livdeo reticularis
mainly used to add on to levodopa and help reduce the dyskineasia assocaited with it
- also seen to help the tremor
how to combat the confusion and psychosis of PD
always attempt to simplfy the medications & use the most effective and lowest dose possible of dopamenergic agents
to combat the halucinations
- Nuplazid
to combat the psychosis (use anti-psychotics with the lease extrapyramidial side effects)
- quetiapine
- cloazapine
The role of Deep Brain Stimulation in PD
DBS
- microelectrodes implanted into the Basal ganglia: eithe rhte STN or the GPinternus to help with PD symptoms
- an implantable pulse generator is there to stimulate via high frequency
- its adjustable and reversible - safe once implanted
Indications
- those with refractory symptoms or medication side effects
- those who respond well to medication (but maybe cant tolerater SE) are best canidates with best outcomes of DBS
- contraindicated in those with PD dementia
need to have
- neurology
- nerurosurgery and neuropsychology invovled to plan & get full evlauation of pt. on and off medications and see levodopa effects first
Atypical Parkinsonism
Lewy Body Dementia
- early onset dementia
- hallucinations
- cognitive fluctuations are a key: very drastic changes
Corticobasal Degeneration
- loss of sensation
- alien limn phenomenon
Progressive Supranuclear Palsy
- gaze palsy
- early cognitive and gait impairments
- speech impairments
multisystem atrophy
- autonomic insuffiency
- incontinence
- cerebellar ataxia
all of these atypical parkinsonsim’s will not respond well to the use of levodopa
what type of medications will cause drug induced parkinsonism
Dopamine Receptor Blockers
- things which deplete dopamine thus mimicking PD
Typical Antipsychotics
- haldolol, phenothiazine, pimozide
Atypical Antipsychotics
- risperidone, olanzapine, ariprazole, ziprasidone
Dopamine Depleteing Agents
- Reserpine, tetrabenzine
Anti-Emitics
- Metoclopramide!!!
