PD Flashcards
What is Parkinson’s disease?
Chronic, progressive, neurodegenerative disorder
- Characterized by motor and non-motor symptoms - Caused by depletion of dopamine producing neurons in the substantia nigra of the basal ganglia - Presence of Lewy bodies (alpha-synuclein aggregates) in residual dopaminergic cells
Etiology
Cause is largely unknown for most people diagnosed with PD
PD is not considered a hereditary condition
Likely combination of genetic risk factors and environmental factors
Several genes related to PD have been identified:
- Mutations in the LRRK2 gene have been found to be the greatest genetic contributor to PD 1
- (PARK 1) – first gene identified
- Parkin gene (PARK 2), LRRK2, PARK7, PINK1, SNCA gene
Environmental factors:
Occupation
Rural living
Oxidative stress
Pesticides, methamphetamine/amphetamine use
Rare cases of PD caused by single genetic mutation passed from generation to generation resulting in great number of PD within an extended family
What are other etiologies of parkonsonism?
Parkinsonism
Drug-induced
Vascular
Cerebrovascular disease
-Parkinson-plus syndromes
Progressive supranuclear palsy (PSP)
Multi system atrophy (MSA)
Corticobasal ganglionic degeneration (CBD)What drugs can induce parkonsonism?
Phenothiazines – typical antipsychotics (Thorazine, Prolixin); Compazine
Butyrophenones - Haldol
Benzamides – atypical antipsychotics
What is the etiology of PD?
Estimated to be 1 million people in US with PD and 5 million worldwide
Affects 1% of the population over age of 65
Approximately 60,000 new PD cases each year
Family history in 5-10% of patients
Men may have a slightly higher risk of developing PD
Name some assessment tools used to evaluate people with PD
United Parkinson’s Disease Rating Scale (UPDRS)
-Subjective reports and objective exam of motor and non-motor symptoms
Hoehn and Yahr Scale: Stages 1-5
Schwab and England ADL scale: 10- 100%
Patient diaries: Records length of daily ON/OFF/Dyskinetic periods
Olfaction: BSIT
Caregiver reports
Depression screen: GDS, PHQ-9
Cognitive screen: Montreal Cognitive Assessment (MoCA)
Describe the stages of Hoehn & Yahr Scale
Stage 1 – unilateral, minimal to no functional impairment
Stage 2 – bilateral without balance impairment
Stage 3 – Still independent, balance problems
Stage 4 – More disabled, unable to live alone, can stand and walk unassisted
Stage 5 – wheelchair or bedbound unless assisted
How do you formulate a diagnosis for PD?
PD is a clinical diagnosis
Careful history with chronology of symptoms
Thorough physical exam
Positive levodopa response reinforces a PD diagnosis
Challenges in dx: gradual onset, variable, nonspecific, subtle changes could be attributed to aging
No tests or studies that can confirm diagnosis – only autopsy
Abnormal olfactory test is supportive of PD diagnosis
What is DAT-SPECT
DAT-SPECT is a diagnostic tool that can identify patients with parkinsonism:
- Uses an IV administered radioactive tracer that allows for visualization of the dopamine transporters in the brain
- Cannot differentiate between PD and other forms of parkinsonismsuch MSA, PSP, CBD, or LBD
What are general physical assessment findings?
Skin changes (seborrheic dermatitis) Orthostatic hypotension Musculoskeletal changes due to aging or injury
What are neuro exam findings?
- Mental status: Depression, anxiety, cognitive changes
- Cranial nerves: Olfaction, limited upgaze, masked facies, hypophonia
- Motor: cogwheel rigidity
- Reflexes: + Myerson’s sign
- Sensory: objectively normal; often subjective symptomatology
- Coordination: decreased RAM speed
- Gait: decreased arm swing, stooped posture, short or shuffling steps
- MS: tremor
What is the Myerson’s sign?
Myerson’s sign or glabellar tap sign is a clinical physical examination finding in which a patient is unable to resist blinking when tapped repetitively on the glabella, the area above the nose and between the eyebrows. It is often referred to as the glabellar reflex.
DDX PD
Parkinson-plus syndromes including - Progressive supranuclear palsy - Multiple system atrophy - Lewy body disease Vascular parkinsonism Drug-induced parkinsonism Multifactorial gait disturbance Essential tremor
When might you think that PD is an incorrect diagnosis?
Other diagnoses should be considered if:
- No benefit from levodopa - Initial bilateral symptoms - Gait-predominant symptoms only - History of CVA, diabetes, psychiatric comorbidities, use of illegal drugs or antipsychotics - Abnormal eye movements upon exam - Early autonomic symptoms - Dementia or psychosis within one year of diagnosis
What are the cardinal motor symptoms of PD?
TREMOR
BRADYKINESIA
RIGIDITY
(POSTURAL INSTABILITY)
Discuss the tremor seen in PD
Not all PD patients present with or develop a tremor!
In 70% of cases, tremor is the first symptom
“Pill rolling tremor” is most prominent in fingers and hand
Involuntary movement that commonly affects the limbs and/or jaw
Present during rest and resolves with action
Starts unilaterally
Increases with stress, anxiety, excitement
Ceases with sleep
50% of patients presenting with tremor do not have PD.
Discuss bradykinesia seen in PD
Slowness of movement
Decrease in: Walking speed Eye blinking Facial expression Eating and chewing
Discuss rigidity seen in PD
Muscular stiffness and increased muscle tone
Patients are usually unaware of rigidity, more troubled by slowness
Detected on exam, described as “cogwheeling”
Can be brought out by distracting maneuvers in the contralateral limb
Describe postural instability seen in PD
Loss of postural reflexes, resulting in falls
Some patients will fall several times a day
Falls in PD results in tremendous morbidity and mortality
Gait impairment caused by:
- Shuffling - Festination - Freezing of gait
Describe additional motor symptoms seen in PD
Reduced arm swing
Stooped posture
Dystonia (involuntary muscle contraction/abnormal posture holding of limb)
Micrographia (small handwriting)
Hypomimia (reduced facial expression)
Fine motor impairmentDiscuss n on-motor symptoms of PD
Early in disease process, fatigue is common
May present before or after the onset of motor symptoms
Often reported as more disabling than motor symptoms
Recognition and treatment of non-motor symptoms can help improve quality of life for PD patients and their caregivers
Discuss psychiatric disorders common in PD
Depression: most common affecting 40-50% of PD patients
- May be overlooked and undertreated due to shared characteristics with PD, such as reduced energy levels, sleep disturbances, eating changes, and reduced facial expressions.
Anxiety: 30-40% of PD patients
- Often linked to motor fluctuations (OFF time)
- May manifest in PD patients as generalized anxiety, social phobia, panic attacks, OCD
Discuss cognitive disorders seen in PD
Some degree of cognitive decline occurs in every patient
In at least 20% of patients, symptoms will progress into full dementia syndrome
Dementia associated with a poorer prognosis as levodopa response typically lessens and pharmacological side effects are more problematic
Early onset of dementia (within 1 year of PD) suggests Dementia with Lewy bodies
Rule out metabolic abnormality (B12 deficiency), delirium (UTI), medications (benzos, anxiolytics)
Discuss sleep abnormalities common in PD
Occurs in >70% of patients
- Insomnia - Excessive daytime sleepiness - Vivid dreaming - Restless leg syndrome - Periodic limb movements - REM Sleep Behavior disorder (RBD) - Inadequate Sleep Hygiene
Discuss autonomic dysfunction seen in PD
- Constipation
- Orthostatic hypotension
- Urinary incontinence, retention, urgency
- Erectile dysfunction
- Drooling
Discuss speech and swallow changes seen in PD
- Hypophonia and Dysarthria: low volume and unclear articulation of speech
- Swallowing problems: choking and coughing during meals, pills getting “stuck”
Discuss pain as a symptom of PD
- 40-75% of patients with PD experience pain as a non- motor feature of the disease
- Occurrence of pain in PD is inconsistent and poorly understood
- For a minority of PD patients, pain is more disabling than the motor symptoms of PD.
What is Levodopa and how is it used?
( gold standard) Developed in the 1960’s First major breakthrough in treatment of PD Converted to dopamine in the brain Known as Sinemet ( carbidopa/levodopa) Carbidopa allows levodopa to cross the blood-brain barrier and reduces nausea Assists in confirming diagnosis Must titrate slowly due to risk of NMS
What are the various levodopa formulations available?
Sinemet (Carbidopa/Levodopa)- IR and CR
Parcopa – dissolvable form
Stalevo ( Carbidopa/Levodopa/Entacapone)
Rytary ( Extended release) combines both IR and CR
Duodopa pump- PEG delivery- runs 16 hour/day
Inbrija- inhaled form (NEW!)
What is entacapone?
Comtan
Blocks COMT enzyme thereby allowing greater portion of levodopa to cross into the blood brain barrier
Typically used to reduce motor fluctuations
Must be given with the Sinemet
What are dopamine agonists and when are they used?
Includes Requip ( Ropinirole) and Mirapex ( Pramipexole) and Rotigitine patch
Often used as first-line agent in early PD
Used in conjunction with Sinemet and other dopaminergic medications.
Must be titrated and tapered slowly due to risk of NMS
What is Rasagiline?
( Azilect)
Monoamine oxidase type B ( MAO-B) inhibitor that blocks the breakdown of dopamine
Reduce “off” time and improved motor fluctuations
Does not increase tyramine sensitivity.
What is apomorphine?
( Apokyn)
Non-ergoline dopamine agonist in injectable (subcutaneous) form labeled for the acute, intermittent treatment of “OFF” episodes
Pt must be titrated on this in a clinical setting to determine response
Used as a rescue medication
What is amantadine?
( Symmetrel) first used as an anti-viral drug For tremor and dyskinesias Must be used in caution with elderly and dementia as it can cause confusion Rimantadine (Flumadine) causes less confusion
What are common side effects of dopaminergic therapy?
Nausea/GI side effects Excessive daytime fatigue Visual hallucinations and illusions Dyskinesias Orthostatic hypotension Pitting edema Impulse control disorders ( ICD’s)
What does initial medication management look like for a pt with PD?
Sinemet- most common choice
Rasagiline
Agonist- Mirapex or Requip
May see patients on varied regimens.
How might you treat non-motor symptoms common in PD?
Some non-motor symptoms may respond to dopaminergic therapy however standard treatment strategies for individual symptoms are often applied
Depression: antidepressants, psychotherapy
Anxiety: SSRI, anxiolytics, psychotherapy
Dementia: Cholinesterase inhibitors
Sleep: Clonazepam for RBD/ Melatonin
Drooling: gum, hard candy, atropine drops, Botox
Constipation; stool softeners, laxative, diet changes
What non-pharm approaches to PD management should you consider?
Diet: plant based diet, protein intake and Sinemet (breaks down faster! take an hour before lunch!), Brain wellness clinic
Exercise: slow disease progression, beneficial for gait impairment and postural stability, mood, constipation
Support: support groups, patients and family education, community resource
What are dyskinesias?
- abnormal/involuntary movements of the head, neck, trunk and/or extremities
Result of high dopamine levels
Some patients do not notice dyskinesias, while others are faced with exhaustion, weight loss, functional impairment and social embarrassment
Dyskinesias are not true symptoms of PD but side effects of anti-PD medications
Respond well to DBS and medication reduction
Most patients prefer to be dyskinetic versus “frozen”
What are fluctuations?
Pt fluctuates between states of good symptom control ( “ON”) and poor symptom control ( “OFF”)
Can be both motor and non-motor symptoms
Direct relationship to medication dosing
“roller coaster ride” with ups and downs throughout the day
Can be predictable, unpredictable, sudden
Pts can be aware of fluctuations and adjust their schedules accordingly
What does treatment and management of moderate disease look like?
typically requires a combination approach to pharmacotherapy as motor symptoms progress. Pt may be on 1-4 PD medications ( not including those to address complications) taking up to 5 doses a day
Management strategies of moderate disease often focus on achieving a balance between motor control and alleviation of disease and treatment complications… becoming a tug-of-war game
What pharmacologic treatments exist for adverse effects of PD/PD treatment?
Pharmacological therapy for adverse effects
Nausea- add carbidopa or Domperidone
Excess daytime fatigue- Ritalin, Provigil
Motor fluctuations- Comtan or change Levodopa formulation
Sudden off periods- consider apokyn
Visual hallucinations- Seroquel, Clozaril or Pimavanserin ( NO HALDOL or other antipsychotics)
Dyskinesias- Amantadine
Orthostatic hypotension- Florinef or Midodrine.
Discuss psychosis as a complication of PD and management
20-40% of PD patients will have psychosis during their illness ( VH, illusions, fixed delusions)
Result of high dopamine levels or dementia
Pts typically retain insight early on but lose insight as dementia progress
Meds that are safe in PD: Seroquel, Clozaril and Pimavanserin (Nuplazid)
Do not use typical antipsychotics/neuroleptics
Rule-out other causes: infection, new meds
What surgical option exists for PD management?
Deep Brain Stimulation ( DBS)
- uses electrode leads and stimulator device - targets either the subthalamic nucleus (STN) or the globus pallidus interna (Gpi) for treatment of PD - “electric Sinemet”
What are the advantages of DBS?
Provides benefit for tremor, bradykinesia, gait disturbance, dyskinesias, motor fluctuations
Can be performed bilaterally at one time
Reversible-equipment can be removed at any time with no destruction of brain tissue
Adjustable-parameters can be adjusted using programming equipment and patients can make minor adjustments themselves using Access device
Newer battery is rechargeable.
What are disadvantages of DBS?
Implanted foreign body - risk of infections Equipment failures Battery replacement- rechargeable Cost of equipment Possible electromagnetic interference- Time and effort needed for programming Side effects
Who is a candidate for DBS?
Idiopathic Parkinson’s disease, responsive to Sinemet, not end-stage disease
Optimized pharmacological treatment
Cognitive function intact
Realistic expectations- not a cure
Acceptable medical history- surgical risk
Willing to return for reprogramming
Discuss management concerns of advanced disease
A continual balancing act between motor control, non-motor comorbidities, and treatment complications.
Pharmacological therapy often becomes less beneficial and may need to be reduced as complications become more prominent.
Dementia and psychosis can be the primary focus of care as the disease progresses.
Disease presentation will often fluctuate with patients decompensating and then rebounding.
How can you determine if an acute emergency exists?
PD patients with advanced disease can make frequent trips to the ER
Cognitive fluctuations, psychosis, dementia, and pain can mask signs and symptoms of a true acute emergency
It is important for caregivers and healthcare providers to know what is “normal” for that individual patient before deciding if an ER visit is necessary
What are late stage complications of PD?
Dementia Recurrent pneumonia Dysphagia Communication barriers Weight loss Urinary incontinence Infections Pain Caregiver burden
What are psychosocial considerations of end-stage PD?
Advanced care planning Home health care and services Respite care and services LTC placement Palliative Care: Hospice referrals
