Parkinson's Disease Pre Module and 101 Flashcards
The common age of dx:
60 years or older
4% of all with PD are under the age of 50
What 3 conditions fall under the description of “Parkinsonism”?
PD
Progressive Supranuclear Palsy
Multiple Systems Atrophy
What type of dementia can have parkinsonian features?
Lewy Body Dementia
Progressive Supranuclear Palsy signs and symptoms
-can’t look down due to impaired eye movements
-scared appearance
-severe postural extension
-falls in the first year- typically backward
-ONSET: over age 50
** WORSE PROGNOSIS THAN PD
Multiple Systems Atrophy signs and symptoms
-dysautonomia
-parkinsonian and/or
-cerebellar syndrome-ataxia, dysarthria -orthostatic hypotension: 30mm systolic or 15mm diastolic drop
-urinary system- urinary problems usually arise from degeneration in a part of the brainstem that controls urination. Symptoms such as incontinence, leakage, urinary frequency
Cardinal Signs of PD:
rigidity
bradykinesia
resting tremor
postural instability - usually occurs later in the disease process
SUPPORTIVE CRITERIA
-unilateral onset –> then BL
-progressive course
-persistent asymmetry affecting side of onset the most
Possible non-motor signs of Parksinson’s
-cognitive impairment - attention, dual task, dementia
-pain
-depression
-hallucinations
-olfactory loss
-dysautonomia
-sleep dysfunction
-fatigue
What is required for PD diagnosis?
-cardinal signs (bradykinesia plus one other)
-pos response to dop replacement (70-100% improvement)
-type using UPDRS:
–tremor dominant form
–postural instability and gait disorder form
What is the difference between the tremor-dominant form of PD and the postural instability and gait disorder form? (UPDRS)
the PIGD form -
-more problems with instability and gait dysfunction
-more likely to have cognitive deficits
-faster decline –> need medications earlier
What are 4 common medication types for individuals with PD?
DOPAMINE REPLACEMENT: precursor to DA, levodopa crosses the BBB and converts to dopamine; Carbidopa inhibits the breakdown of levodopa peripherally
ex: Sinemet-carbidopa/levodopa (helps prevent vomiting, GI side effects),
Rytary- extended-release carbidopa/levodopa
DOP. AGONIST increases the efficiency of dopamine already in the system —> may delay starting dopamine replacement
-Pramipexole
-Ropinirole
-Rotigotine patch
-Apomorphine (rescue)
DIFFERENT ADMINISTRATIONS POSSIBLE:
-enteral through jejunum tube (duopa)
-transdermal injection
-sublingual, inhaled and nasal spray preparations being studied
COMT INHIBITORS -slows down the breakdown of dopamine
-tolcapone
-entacapone
-opicapone
MAO-B INHIBITORS- slows the breakdown of dopamine –>
-may be used early in the disease
-may have a neuroprotective effect
-rasagiline
-selegiline
Anticholinergics - bind to and block ach receptors
Adenosine A2A Receptor Antagonist
Botulinum Toxin for dystonia
Deep brain stimulation for PD:
-for medication-resistant tremor
leads go under the skin and are implanted deep into the brain –> wires go through a burr hole in the skull
the pulse generator is under the clavicle at the anterior chest wall
has the potential to decrease the amount of meds needed
LEADS GO IN:
-globus pallidus
-subthalamic nucleus
-thalamus
SE
-cog impairment, worsened balance, dysarthria
GOLD STANDARD MEASURES USED TO DESCRIBE PD
UPDRS
Hoehn and yahr
(schwab and england - not listed as gold standard)
Performance measures for PD:
freezing of gait
PDQ-39
mobility and function
look to SG for Hoehn and Yahr Classifications
look there
UPDRS CATEGORIES AND TOTAL POINTS
- mentation, behavior, mood
- ADLs
- motor examination
- complications of meds
total score: 176 points
motor subscale: 108 points
PARKSINSON’S DIAGNOSIS
-a chronic, progressive, neurodegenerative condition that often presents later in life
MUST INCLUDE:
*UKPD Brain Bank Criteria
-bradykinesia must be present plus ONE: resting tremor, rigidity, postural instability(not caused by vision, vestibular, cerebellar dysfunction)
*UPDRS parts I-IV to assess progression, medication response
*Hoehn and Yahr Staging
*Time
*Carbidopa-Levodopa trial
*Imaging - MRI (rule out structural impairment), DAT scan
*autonomic test, smell test, skin biopsy (abnormal protein in ppl with PD)
SUPPORTIVE CRITERIA:
-unilateral onset, persistent asymmetry
-responsive to levodopa
progressive
-levodopa induced dyskinesia
-prodromal symptoms (RBD, loss of smell) –> before the major signs or symptoms start
EXCLUSION
-strokes/head injuries repeated
-anti-dopaminergic agent exposure
-encephalitis
-sustained remission
-poor response to L dopa
-other neurologic signs (cerebellar signs, early dementia, supranuclear palsy)
epidemiology of PD
more in men 3:2
fastest growing neurodegenerative dod in terms of disability, prevalence, and death
RISK FACTORS
-age
-exposures- agent orange, pesticides
-reduced risk: cigarettes, caffeine
-peak: 85-89 years old
pathophysiology of PD
MACRO
-small changes macroscopically
loss of neurons in substantia nigra pars compacta (brainstem) and locus coeruleus
-the death of DA neurons in substantia nigra (basal ganglia)
-30% loss–> motor symptoms onset
-dopamine throughout the striatum is lost (basal ganglia)
MICROSCOPICALLY
alpha-synuclein protein –> aggregates into lewy bodies with mutation
Substantia nigra and connection with caudate and putamen of basal ganglia
the DA neurons of the substantia nigra project to the caudate and putamen of the striatum (BG) –> this pathway makes up the nigrostriatal pathway
Genetics of PD
the complex interaction between genetics and enviro
~15% genetic
LRRK2, GBA, PARK2, PINK1 gene
-may help to determine if someone is a candidate for DBS
COMMON MOTOR SYMPTOMS
resting tremor –> less likely essential tremor
bradykinesia –> slower, smaller movements
–decrement of movement
–interruptions/hesitations
rigidity
postural instability
decreased stride
festination- tiny steps
-FOG
-stooped posture–> camptocormia (abnormal trunk flexion), pisa syndrome (lateral flexion, stooping)
-dystonia–> toe curling, muscle cramps, big toe extension with other phalanx flexion (striatal toe)
non-motor symptoms
psychiatric–> anxiety, dep, apathy
cog impairment (at 20 years of dod –> 80% have dementia)
–PD-MCI, PD-dementia
-dysautonomia
–constipation
–urinary incontinence
–orthostatic hypotension
-dec sense of smell–> hyposmia/anosmia
-fatigue
-sialorrhea (decreased swallowing reflex –> drooling
-hypophonia, dysarthria –> quiet speech, dec muscle strength of muscles needed for speech
-pain
-sleep: insomnia, Rem sleep behavior disorder (RBD), RLS/PLMS (restless leg/periodic limb movements of sleep
ophthalmology
-convergence insufficiency
-saccadic intrusions
-eyelid opening apraxia
autonomic
-neurogenic orthostatic hypotension
- hyperhidrosis
RBD characteristics
act out dreams
can happen 10-20 years before diagnosis of the condition
Symptoms of pre-motor/prodromal period
constipation
RBD
EDS- excessive daytime
sleepiness
hyposmia
depression
What is is a symptom of PD that usually only happens in the mid-advanced stages of PD?
psychosis
Describe the typical progression and clinical course from preclinical phase onward:
preclinical phase -2 - (-6 )years
the onset of levodopa therapy/diagnosis–> honeymoon period - 0-3 years
motor complication period- 3-8 years
resistant symptoms - 8-15 years
cognitive decline ~15-20 years
What is a DAT scan?
dopamine transporter scan
SPECT scan
Ioflupane I 123 injection
tags DA transporters in striatum–> demonstrates integrity of nigrostriatal nerve terminals
-loss of neurons, loss of signal
-cannot distinguish between other forms of PD
Differential diagnosis for PD
TAUOPATHIES
-progressive supranuclear palsy (early falls, wheelchair sign, can’t look down)
-cortical basal syndrome/degeneration
SYNUCLEINOPATHIES
-multisystem atrophy (dysautonomia, possible cerebellar signs)
-dementia with LB (early dementia, cognitive fluctuation)
TOXINS
-pesticides
-MPTP (contaminated synthetic heroine)
-agent orange
-manganese, lead
-alcohol withdrawal
DRUG-INDUCED
-dopamine antagonist anti-psychotics
-VMAT2 inhibitors
-lithium
-valproic acdid
types of tremors not related to PD
essential tremor
dystonic tremor
holmes/rubral/midbrain/cerebellar outflow tremor
What other disorders did we learn about that can parkinsonian like symptoms?
AD
HD
Spinocerebellar ataxia
What is the only disease modifying therapy for parkinson’s
exercise
(diet and sleep are two other lifestyle modifications)
SEs dopaminergic therapy
GI distress (nausea, vomiting)
Dyskinesias - involuntary, erratic, writhing movements of the face, arms, legs
or trunk. Choreiform
Orthostatic hypotension
Decreased B12/folate absorption
Impulse control disorders (more so with the dopamine agonists)
Hallucinations
Dopamine dysregulation syndrome (DDS) (can become addicted)
Parkinsonism-Hyperpyrexia Syndrome (acute withdrawal, neuroleptic-like
malignant syndrome)
non-motor treatment
Anti-depressants/anxiolytics
Bowel regimen
Anticholinesterase Inhibitors (donepezil, rivastigmine) –> MAY HELP Freezing of Gait
Sleep
RLS/PLMS (ropinrole,
gabapentin, etc)
RBD (melatonin, clonazepam) Sialorrhea
Botulinum toxin injections,
atropine drops
Focused ultrasound - advanced therapy
With focused ultrasound (FUS), doctors use ultrasound beams to destroy brain cells that cause movement problems. (It’s a bit like using a magnifying glass to focus sunlight rays on a leaf to make a tiny hole.)
permanent lesion via sonification
working towards bilateral treatment
less cog impairment possible
Duopa
A Carbidopa Levodopa Gel that
is continuously delivered by a
pump through a J tube to the
small intestine
more regulated and on time
bypasses the stomach
enteral admin
