Parkinson's Disease Flashcards
Rising neurological disorder
Parkinson’s disease
Life expectancy for Parkinson’s
68-69 males
75-76 females
Broader term for PD
Parkinsonism
Parkinsonism is a combination of (3)
Rest tremor, rigidity, bradykinesia
Parkinson’s takes up how many percent of Parkinsonism?
77%
Parkinson plus syndromes take up how many percent of Parkinsonism?
12%
Drug induced, extrapyramidal symptoms take up how many percent of Parkinsonism?
5%
Classification of Parkinsonism (4)
Primary/Idiopathic Parkinsonism
Secondary Parkinsonism
Heredodegenerative Parkinsonism
Multiple-System Degeneration / Parkinsonism-Plus
Types of Primary / Idiopathic Parkinsonism (2)
Parkinson’s disease
Juvenile parkinsonism
Types of Secondary Parkinsonism (2)
Infectious, Drugs, Toxins, Vascular, Trauma
Stroke, TBI
Types of Heredodegenerative Parkinsonism (2)
Huntington’s
Wilsons
Types of Multiple-System Degeneration / Parkinsonism-Plus (4)
PSP (progressive supranuclear palsy aka Steele Richardson Olszewski)
CBD (corticobasal degeneration)
LBD (lewy body dementia)
Multisystem atrophy
○ Striatonigral degeneration
○ Olivopontocerebellar atrophy
○ Shy Drager syndrome
Described by James Parkinson in 1817 as “the shaking palsy”
Parkinson’s disease
PD is a ____ disorder of the CNS
Chronic progressive disorder
PD results from degeneration of ____ producing cells in the substantia nigra
Dopamine-producing cells
Substantia nigra is located where?
Midbrain
T/F: PD is the 2nd most common neurodegenerative disease after Alzheimer’s Disease
True
T/F: PD is the 2nd most common neurodegenerative disease after Alzheimer’s Disease
True
T/F: PD is age related, progressive disorder
True
___ is markedly decreased in PD
Dopamine
Famous people with PD (7)
Muhammad Ali
George Bush
Yasser Arafat
Mao Zedong
Pope John Paul II
Michael J. Fox
Adolf Hitler
Prevalence of PD
100-180 in a million
4-20 per 100,000
Rising with age
Male:female 3:2
Myths of PD (3)
Not true:
Only old people get PD
The only thing that people have with PD is shaking
Only the person with PD is a ffected by the disease
Parkinson’s disease is a neurodegenerative disease associated with _____ of the substantia nigra and loss of dopaminergic input to the basal ganglia (extrapyramidal system)
Depigmentation
T/F: In healthy individuals, dopamine is produced by neurons that project from the substantia nigra to the neostriatum (which include caudate and putamen) and globus pallidus
True
The loss of dopamine-producing neurons in the substantia nigra results in the ______ between _____, and the excitatory neurotransmitter ______
Imbalance between dopamine (an inhibitory neurotransmitter) and acetylcholine
T/F: Even if there is a normal rate of production of Acetylcholine but diminished dopamine secretion (less inhibition), it will be a balance state thus more kinetic movement
False: imbalance
Medication is also given to combat PD or reduce activity of the cholinergic system
Anticholinergic medication
Medication is also given to combat PD or reduce activity of the cholinergic system
Anticholinergic medication
Etiology of PD (3)
Unknown
Proposed etiology
○ Influence of aging
○ Environmental toxins
○ Genetic susceptibility
Oxidative stress
Alterations in the substantia nigra of patients w/ PD suggestive of oxidative damage
Oxidative Stress Theory
Evidences that supports oxidative damage (6)
Increased iron levels
Lack of compensatory rise in isoferritins
Increased aluminum levels
Reduced glutathione levels
Selective defect in complex I of mitochondrial
respiratory chain
Evidence of oxidative damage to
■ Lipids, DNA, Proteins, Tyrosine-containing molecules
Genetics of PD: Onset
Young onset PD, onset <40 y.o.
Juvenile onset PD, onset <20 years old
Major cause of young onset autosomal recessive PD and isolated juvenile PD
Parkin mutation
Mutations in autosomal dominant PD
ɑ synuclein and ubiquitin carboxyhydrolase
T/F: Mutations give rise to problems in protein clearance, accumulation of excessive protein that can be harmful to the neurons
True
Loss of dopaminergic (DA) cells located in substantia nigra; most symptoms do not appear until striata DA levels decline by at _______
70%-80
Pathophysiology of PD
Use of SPECT (single-photon emission computerized tomography) & PET (positron emission tomography) Scan for research purposes
Degeneration of substantia nigra
Reduced production of dopamine
○ Commonly used for research purposes
Clinical manifestations of PD (TRAP)
Tremor (most common: rest tremors)
Rigidity
Akinesia/Bradykinesia
Postural instability
Characteristics of Tremors (5)
4-6 Hz
Resting (disappears with voluntary movement, sleep)
Accentuated by stress and anxiety
Pill rolling (at rest)
Additional:
Essential Tremor & Physiologic Tremors are 8-12 Hz
and are kinetic and/or postural (during movement)
Resistance to passive movement of limbs
Involuntary hypertonia of skeletal muscles
Limb rigidity
Manifestations of limb rigidity
Cogwheeling
Not spastic (like a swiss knife initial resistance upon opening but then “gives”)
Decreased speed and amplitude of complex voluntary movement
Slowness in initiating and sustaining movement
Fragmented
Bradykinesia
How to elicit bradykinesia
Micrographia: asking them to write where writing becomes smaller over time
Tapping fingers: compare the left and right; will get slower
Twiddling of Hands: will present unilaterally then bilaterally
Pinching and Circling
Tapping with the Heel
How to elicit limb rigidity
When extending limb, there’s rigidity but not spastic
Rigid over the ROM, can slowly extend extremity
Tendency to fall, keel balance to one side → fractures
● Prone to falls & fractures (humerus, hip, femoral)
Initial phase of PD: others may think it is normal and
only part of aging
Develop stoop posture, angle worsens over time
Postural instability
Major symptoms of PD (5)
● Bradykinesia - slowness in initiation and execution of voluntary movements
● Rigidity - increase muscle tone and increase resistance to movement (arm and legs are stiff )
● Tremor - At rest, when person sits, arm shakes, tremor stops when person attempts to grab something
● Postural Instability - stoop when standing, equilibrium, and righting reflex, lose balance
● Gait Disturbance - Shuffl ing Feet
Hitler’s condition
Micrographia
Diagnosis of PD
Diagnosis depends on clinical findings
Tests to rule out secondary parkinsonism
PET to visualize dopamine in substantia nigra and basal ganglia
SPECT for dx essential tremor, Parkinsonian syndromes or Non-parkinsonian
Clinical criteria of PD (5)
- Presence of at least 2 of the 3 cardinal features of parkinsonism: Tremor, rigidity, bradykinesia
- Presence of at least two of the following:
○ Marked response to levodopa
○ Asymmetry of signs
○ Asymmetry of onset
○ Symptoms usually starts unilaterally - Evidence of disease progression
- Absence of clinical features of alternative diagnosis
- Absence of etiology known to cause similar features
Stage of PD: No clinical signs evident
Stage 0
Stage of PD: Unilateral involvement, including the major features of tremor, rigidity, or bradykinesia; minimal functional impairment
Stage 1
Stage of PD: Bilateral involvement but no postural abnormality
Stage 2
Stage of PD: mild to moderate bilateral disease , mild postural imbalance, but still able to function independently
Stage 3
Stage of PD: Bilateral involvement with postural instability; patient requires substantial assistance
Stage 4
Stage of PD: Severe disease; patient restricted to bed or
wheelchair unless aided
Stage 5
Differential Dx:
Gradual onset; tremor; gait disturbance; slowed movements (bradykinesia)
Resting tremor (limbs), Cogwheel rigidity (limbs)
Idiopathic PD
Differential Dx:
Exposure to haloperidol or metoclopramide
Similar to idiopathic to PD
Drug induced Parkinsonism (secondary)
Differential Dx:
Present for many years; + family history
Tremor w/ arms raised; head involved
Essential tremor
Differential Dx:
Parkinsonism w/ autonomic system dysfunction
Orthos. hypotension (syncope), skin changes
Multisystem atrophy
Differential Dx:
Involuntary movement cognitive or behavioral problem
Chorea; loose tone, early dementia
Huntington’s Disease
HCC: Huntington-Chorea-Cognitive
Exercise, rehabilitation, intervention, nutrition
Non-pharmacological approach
Giving of drugs that can protect the neurons in
the brain
Pharmacological approach
MAO B (Monoamine oxidase-B) such as selegiline
and tocopherol (Vitamin-E) acts as a scavenger
of free radicals
Dopamine agonists serve as scavengers of free
radicals; decrease dopamine turnover, there are increases in oxidative stress
■ Helps in treating PD but also contributed to oxidative stress in the long run
Neuroprotective treatment
Four classes of drugs available (A, P, D, I)
Anticholinergics (good for treating rest tremors)
Precursor of dopamine (Levodopa, Carbidopa)
Direct-acting dopamine agonists (Bromocriptine, Perogoiide)
Indirect-acting dopamine agonists
-Decrease re-uptake (amantadine)
-Decrease metabolism (selegiline)
Drug Therapy for treating associated symptoms (e.g. pain, mood problems) (3)
○ Tricyclic antidepressants
○ Beta-Blockers
○ Antihistamines
Treatment Plan (4)
● Age
● Severity of Sx
● Cognitive function
● Comorbidities
○ Medications are already prescribed and may interact with anti-PD medications
Treatment Strategies (2)
● Symptomatic treatment - look at the 4 classes of drugs
○ Levodopa
○ Amantadine
○ Anticholinergics
○ COMT inhibitors
○ Surgery
● Symptomatic with Neuroprotection
○ Dopamine agonists ○ Selegiline
Gold standard for PD
Levodopa
To reduce peripheral conversion of levodopa so that more amount of levodopa can enter the CNS and cross the BBB
Carbidopa-levodopa combination
Taken up by dopamine nerve terminals in the striatum
Converted to dopamine by dopa decarboxylase
Released and acts at the dopamine receptors
Levodopa
E ffects and Precautions of Levodopa
○ Mainstay of therapy
○ Produce immediate symptomatic response thus
being part of the diagnostic criteria for clinical
diagnosis of PD
○ Long-term use leads to dyskinesias and motor
response fluctuations (“on-off ” phenomenon)
○ Development of nonlevedopa-responsive
features (freezing, autonomic dysfunction)
○ May induce oxidative stress due to increased
dopamine turn over and free radical formation
○ Major side e ffects: Nausea, hallucinations,
orthostasis (drop in BP)
Block muscarinic cholinergic receptors
Anticholinergic
Block muscarinic cholinergic receptors
Anticholinergic
Purpose of anticholinergic
Restore motor function by reducing acetylcholine in
the setting that dopamine is already reduced in PD
→ less hyperkinesis
Effects and precautions of anticholinergic
○ Can be effi cacious for tremor and dystonia
○ May be used as a secondary pharmacologic
option
○ Peripheral side e ffects - dry mouth, blurred
vision, urinary retention, constipation
○ Central nervous system side eff ects - confusion,
memory loss (one of the long term e ffects)
Indirect dopamine agonist
Amantadine
Discovered serendipitously because it is originally an
antiviral medication
Amantadine
E ffects and Precautions of Amantadine
○ Improves bradykinesia and tremor
○ Can be used as monotherapy or as adjunct
therapy to levodopa
○ Antiparkinsonian mode of action is not
completely understood
○ Short term benefits
○ Adverse e ffects include: restlessness, confusion,
depression, nausea, hypotension
● Popular drug before
● Monoamine oxidase-B (MAO-B) inhibitor
● Reduces dopamine metabolism
○ Less breakdown of dopamine
○ Has neuroprotective eff ects
○ Gone down in popularity d/t many
contraindications with other drugs
Selegiline
E ffects and Precautions of selegiline
Postulated to have neuroprotective eff ect
■ Reduce oxidative stress
■ Reduce free radical production
○ No benefit in reducing levodopa-induced motor fluctuations
○ Has mild symptomatic e ffects
○ Nausea, hallucinations
● Catechol-O-methyl-transferase
● Reduces dopamine breakdown
● Not very popular in the market d/t limited
improvement but it can be used in conjunction with
levodopa
COMT inhibitor
Effects and Precautions of COMT inhibitor
○ Increases the bioavailability of levodopa → good
to be combined
○ Useful adjunct in early stage of PD and in
patients w/ mild response fluctuations → delays
onset of more severe PD
○ Downside:
■ Reported cases of rare hepatocellular injury*
■ Possible neurotoxicity in PD**
Effects and Precautions of COMT inhibitor
○ Increases the bioavailability of levodopa → good
to be combined
○ Useful adjunct in early stage of PD and in
patients w/ mild response fluctuations → delays
onset of more severe PD
○ Downside:
■ Reported cases of rare hepatocellular injury*
■ Possible neurotoxicity in PD**
No longer available in the market
A selective and reversible inhibitor of COMT and
is used as an adjunct to levodopa/carbidopa
therapy
Inhibits COMT both peripheral and centrally
Tolcapone
T/F: COMT is the main enzyme responsible for peripheral and central metabolism of catecholamines, including levodopa. Addition of a COMT inhibitor results in the doubling of the elimination half-life of levodopa and in increased oral bioavailability of levodopa by 40-50%
True
Surgical options for PD
● Pallidotomy
● Thalamotomy
● Thalamic stimulation
● Transplantation of fetal cells
● All of which showed mild improvement in the Sx of PD
A pallidotomy entails the surgical resection of
parts of the globus pallidus
Improves contralateral dyskinesia
Globus pallidus internus (Gpi) Pallidotomy
High-frequency stimulation that induces functional inhibition of target regions of the brain by implanting an electrode into a target site and connecting the lead to a subcutaneously placed pacemaker
Pt can control it to stimulate the areas and regulate the abnormal Sx of PD
Quite expensive (1-2M pesos)
Deep Brain Stimulation
Implantation of embryonic dopaminergic cells
into the denervated striatum to replace degenerated neuronal cells
DID NOT REALLY SHOW any strong evidence that it
can help in the improvement of Sx
Fetal nigral transplantation
Nonpharmacological management (4)
Education
Support
Exercise
Nutrition
Education
Early stage:
● Selective information
● Aimed at promoting general health
● Refer to PD organization
● Referred to PT early on
Advanced stage:
● Problem oriented
Support
Early stage:
● Emotional needs assessment
● Support network assessment
● Financial / occupational counseling
Advanced stage:
● Psychological counseling (d/t PD dementia or depression)
● Respite care
● Need assistance
Exercise
Early stage:
● Aerobics, stretching
● Improves mood, mobility
● Improves postural equilibrium reaction
Advanced stage:
● Physiotherapy referral
● PD exercise group
● Energy conservation techniques
Nutrition
Early stage:
● Balanced diet
● Fibers and fluids vs constipation (caused by meds)
● Calcium vs increased bone mass loss
Advanced stage:
● Dietetic referral
● Help preparing food
● Meal deliveries
● End stage → tube fed (nasogastric or gastrostomy tube)
Secondary effects of PD (4)
● Cardiovascular e ffects
○ Including orthostatic hypotension and arrhythmia
● Gastrointestinal eff ects
○ Including constipation and hypersalivation
● Genitourinary e ffects
○ Including increased urinary frequency, impotence
● Central nervous system e ffects
○ Including hallucination, depression, and psychosis, dementia
PD late disabilities divided into two groups
Levodopa-related Disabilities
Non-levodopa-related Disabilities
■ Include MOTOR fluctuation, dyskinesia, neuropsychiatric toxicity (hallucinations, psychosis), and reduced response
■ Too much MOVEMENTS, orofacial movements, chewing or tongue movements, dystonic movements
Levodopa-related disabilities
Include COGNITIVE impairment, instability
resulting in more frequent falls, gait disturbance, incontinence, dysphagia (di fficulty swallowing so they choke a lot), and speech disturbance, pneumonia.
Non-levodopa related disabilities
Urinary urgency
oxybutynin
UO: urgency-oxibutynin
Urinary retention
apomorphine (not readily available in PH)
RA: retention-apomorphine
Constipation
increased fiber diet, polyethylene glycols, laxatives
Tenesmus (feeling the need to pass stools even if bowel is empty)
clonazepam, apomorphine, relaxants like
benzodiazepines
Hypersalivation
antihistamine, anticholinergic
Dysphagia
liquid levodopa (not available in PH),
gastrostomy or nasogastric tube feeding
Sweating crises
3-blockers, anticholinergic agents
Daytime sleepiness
Selegiline
SS: sleep-selegiline
Nightmares
amitriptyline (antidepressant), clonazepam (benzodiazepine)
Panic attacks and depression
liquid levodopa, amitriptyline, SSRIs for mood problems
Orthostatic hypotension
domperidone, desmopressin (available in PH)
HDD: hypotension-domperidone-desmopressin
Dysphonia
reduce levodopa dosage, speech therapy
Pain
amitriptyline, fluvoxamine (not used that much anymore), pregabalin
