Parkinsons- Week 3

Question 1

PD definition

Answer 1

slowly progressing neurodegenerative disorder with insidious onset of asymmetric resting tremor, bradykinesia, hypokinesia, and rigidity, sometimes with postural changes

Question 2

pathophysiology of PD

Answer 2

nerve cells in the SUBSTANTIA NIGRA send out fibers to the CORPUS STRATIA, gray and white bands of tissue located in both sides of the brain (direction is important, from substantia to corpus)

Question 3

next step of patho

Answer 3

there the cells release dopamine, an essential neurotransmitter. Loss of dopamine in the corpus stratia is the primary defect in PD.

Question 4

pathological changes in PD

Answer 4

dark “moustache” that represents the substantia nigra almost disappears
classical round proteinaceous body- known as Lewy body- considered pathological hallmark of PD**

Question 5

incidence/ epidemiology of PD

Answer 5

1% of population worldwide
mean age of onset 65 years
equally affects men and women
5- 10% get it before age 40

Question 6

the why’s of PD

Answer 6

older age
smoking
first degree relative (most cases are sporadic but there is a genetic component)

Question 7

more patho of PD

Answer 7

destruction of neural cells in the substantia nigra pars compacta (midbrain) that secrete dopamine = loss of dopamine and dopamine receptor sites (70- 80% of neurons must be dead for symptoms to appear)
Lewy bodies- pathologic hallmark but only found on autopsy

Question 8

diagnosis of PD based on

Answer 8

clinical evaluation

Question 9

parkinsonism

Answer 9

any group of nervous system disorders with symptomts similar to PD

Question 10

motor parkinsonism

Answer 10

is an essential criterion of PD and requires both of the following: bradykinesia & rest tremor or rigidity

Question 11

the true “gold standard” for diagnosis for PD

Answer 11

neuropathologic examination. There are no physiologic tests of blood test for confirming diagnosis of PD

Question 12

Diagnosis of PD based on clinical eval- what is the work up?

Answer 12

history (meds, trauma, family)
physical exam
CT, MRI (r/o other possible causes)
response to Levodopa
PD vs. Parkinsonism
consult neurology

Question 13

the diagnosis of clinically established PD requires ALL of the following

Answer 13

the presence of parkinsonism
no absolute exclusion criteria (no way to say its not PD)
at least 2 supportive criteria
no red flags

Question 14

clinically probable diagnosis of PD

Answer 14

the presence of parkinsonism
no absolute exclusion criteria
the presence of red flags must be counterbalanced by supportive criteria
- if one red flag is present, there must also be at least one supportive criterion
- if 2 red flags, at least 2 supportive criteria are needed
- no more than 2 red flags are allowed for this category

Question 15

clinical presentation- idiopathic PD

Answer 15

bradykinesia
plus tremor (most common sign)
or rigidity (2 of the 3 of bradykinesia, tremor, rigidity need to be present)
postural instability (occurs late in disease)
resting tremor
asymmetry (one side more affected than the other)
good response to Levodopa

Question 16

supportive diagnosis

Answer 16

unilateral onset
masked face (decrease in spontaneous facial expression/ flat expression)
hypophonia, monotonous tone (quiet)
gait disorder, falls (forward tilt of trunk, shuffling gait)
flexed posture
reduced arm swinging
persistent asymmetry throughout the course of the disease with the side of onset most affected

Question 17

bradykinesia

Answer 17

generalized slowness of movement
may be described by pt as “weak, incoordination, tired, stiffness”- all words used to describe the decreased ability to initiate voluntary movement
typically starts distally in arms with decreased manual dexterity of fingers
in legs: dragging, shorter/ shuffling steps, unsteadiness
bradykinesia is eventually seen in all PD patients and is the most common feature
also is the most difficult symptom to describe for patients

Question 18

tremor

Answer 18

resting tremor, usually unilateral
**most common PRESENTING symptom- most noticeable when the tremulous body part is supported by gravity and not engaged in purposeful activities
can be intermittent
side affected usually is the more affected side throughout disease course
usually starts unilateral in 1 hand
can involve legs, lips, jaw and tongue
big caution: the majority of people with tremor do NOT have PD: essential tremor (usually b/l and intention), MS (intention), cerebellar dysfunction (usually intention and with other cerebellar signs)

Question 19

rigidity

Answer 19

increased resistance to passive movement about a joint
occurs in approximately 90% of patients with PD
often begins unilaterally, typically same side as tremor

Question 20

cogwheel rigidity

Answer 20

ratchet pattern of resistance and relaxation

Question 21

leadpipe rigidity

Answer 21

present throughout movement

Question 22

physical exam/ test- rigidity

Answer 22

(seen in 90% of PD) grasp the patient’s elbow at the AC region and slowly flex and extend; or pronate and supinate the forearm-
rigidity may increase when another limb is engaged in voluntary active movement

Question 23

physical exam/ test- bradykinesia

Answer 23

(seen in almost all PD) test the speed, amplitude and rhythm of finger tapping, hand gripping, toe tapping, pronation/ supination. In mild PD will show slowing and decreased amplitude

Question 24

physical exam/ test- rest tremor

Answer 24

(presenting symptom in 70% PD) can be intermittent, can be seen when patient is RELAXED with hands resting quietly on the lap

• can distract patient by asking them to perform mental calculations
• or voluntary repetitive movements with the contralateral limb
• may be seen when walking

Question 25

physical exam/ test- postural reflexes

Answer 25

"pull test" give a sudden, firm pull on the shoulders from behind the patient (be prepared to catch them). Normal postural reflex will maintain balance or take only one step; loss of reflex will take multiple steps or fall

Question 26

physical exam/ test- gait disorder/ falls

Answer 26

observe patient walking down the hall unilateral loss of arm swing small step shuffling stooped posture with flexed arm

Question 27

other motor features: craniofacial (common board question)

Answer 27

hypomimia (masked facial expression) * decreased spontaneous eye blink * speech impairment (dysarthria, hypophonia) * sialorrhea (excessive salivation)

Question 28

other motor features: musculoskeletal

Answer 28

``` dystonia myoclonus stopped posture kyphosis scoliosis difficulty turning in bed ```

Question 29

other motor features: visual

Answer 29

blurred vision | impaired contrast sensitivity

Question 30

another caveat about motor features

Answer 30

most of these result from one or more of the cardinal features. example- decreased eye blinking, facial masking, probably a result from a combo of bradykinesia and rigidity

Question 31

non motor symptoms

Answer 31

``` cognitive dysfunction and dementia psychosis and hallucinations mood disorders sleep disturbances fatigue autonomic dysfunction olfactory dysfuntion ```

Question 32

important snapshot

Answer 32

PD traditionally considered a motor system disorder. Now recognized to be a complex disorder with diverse clinical features that include non- motor manifestations The bottom line- PD is a chronic, progressive neurodegenerative disorder characterized by any combo of the 4 cardinal signs: bradykinesia, rest tremor, rigidity and postural instability (presents in later stages of disease)

Question 33

Differentials for PD- drug induced

Answer 33

``` neuroleptics (haldol, perphenazine) dopamine receptor antagonists classic and atypical antipsychotic agents metoclpramide prochlorperazine reserpine ```

Question 34

other differentials for PD- neurodegenerative causes

Answer 34

``` alzheimers dementia with Lewy bodies corticobasal degeneration frontotemporal dementia huntingtons disease multiple system atrophy progressive suprnuclear palsy spinocerebellar ataxias ```

Question 35

other differentials for PD- symptomatic

Answer 35

``` drug- induced infectious metabolic (parathyroid disorders, wilsons disease) post- traumatic toxic (carbon monoxide, manganese) vascular ```

Question 36

other differentials for PD- other

Answer 36

essential tremor normal pressure hydrocephalus SWEDD (scans w/o evidence of dopaminergic deficit)

Question 37

**red flags (if you see these- PD differential, but NOT as likely)

Answer 37

rapid progression of gait impairment (should be slow) complete absence of progression of motor symptoms early bulbar dysfunction inspiratory respiratory dysfuntion severe autonomic failure in 1st five years recurrent falls (more than 1/ year) disproportionate anterocollis absence of any of the common non- motor features of PD otherwise- unexplained pyramidal tract signs bilateral symmetric parkinsonism (should be unilateral)

Question 38

more features suggesting alternative diagnosis- see red flags

Answer 38

``` falls at presentation or early in course of disease poor response to Levodopa symmetric motor signs lack of tremor rapid progression dysautonomia early in disease (urinary urgency/ incontinence, orthostatic hypotension, erectile failure) h/o repeated head injury or encephalitis h/o recurrent strokes ```

Question 39

if in doubt of diagnosis of PD

Answer 39

send to neurology

Question 40

dopaminergic challenge test

Answer 40

assessment of parkinosnian symptoms using the Unified Parkinson Disease Rating Scale (UPDRS) before and after a dose of levodopa or subq apomorphine- positive if a clinically significant improvement in the score (15- 30% or more) 1 hour after administration of levodopa or 20 mins after apomorphine injection - up to 30% of patients may not respond - in patients with mild symptoms that don't interfere with ADLs, don't do the test purely for diagnostic purposes

Question 41

final snapshot- 4W's

Answer 41

PD slowly progressive neurodegenerative disorder of asymmetric resting tremor, bradykinesia, rigidity and sometimes postural changes d/t loss of dopamine and receptors in zone compacta of substantia nigra there are no tests to diagnose like with other chronic neuro disease, PE ROS A&P important consult neuro

Question 42

management

Answer 42

- pharmacological- levodopa, Dopamine Agonists, selegiline, anticholinergic agents, COMT inhibitors, amantadine, MAO B inhibitors The decision to initiate medical therapy is based on the degree to which the patient is functionally impaired, interferes with ADLs - surgical - support

Question 43

Levodopa

Answer 43

replaces the dopamine that is lost precursor of dopamine agonists Sinemet or Madopar (carbidopa- levodopa)- start low, titrate up. once stable, reassess Q 3- 6 months - in early disease: take w/ food to avoid nausea. - advanced disease: take on empty stomach= more effective Adverse effects: nausea, somnolence, dizziness, headache - most effective drug for symptom treatment of idiopathic or Lewy body PD - most effective for akinetic sx, also tremor and rigidity, less postural instability - combined with a peripheral decarboxylase inhibitor (carbidopa) to block its conversion to dopamine in the systemic circulation

Question 44

Levodopa wearing off

Answer 44

most will experience fluctuations in their response to levodopa after 2- 5 years: "wearing- off phenomenon" dyskinesias dystonia more common in pts with young onset so this is the reason you delay treatment until necessary and start at lowest dose possible

Question 45

dopamine agonist

Answer 45

synthetic agents that directly stimulate dopamine receptors adjuncts to levodopa or monotherapy less likely to induce dyskinesias most beneficial in younger patients with early disease ( <60 yo) in combo with other antiparkinsonian drugs for advanced PD will need levodopa in a few years if used as monotherapy AE: hypotension, caution with cardiac disease, N/V, peripheral edema D/C gradually

Question 46

dopamine agonist examples

Answer 46

Bromocriptine (Parlodel) 1.25mg BID Pramipexole (Mirapex) 0.125 mg TID Ropinirole (Requip) 0.25 mg TID Injectable apomorphine (reserved for "rescue" when pt is having a sudden akinetic episode)

Question 47

MAO B inhibitors

Answer 47

Selegiline or Rasagiline 5mg QAM AE: nausea, headache, insomnia (don't take after noon), confusion in elderly, enhances levodopa adverse effects Neuroprotective?? (unclear) delays destruction of neurons and inhibits metabolic breakdown of DA mild symptomatic benefits

Question 48

anticholinergics

Answer 48

Trihexyphenidyl (Artane) 0.5- 1mg BID Benztropine (Cogentin) 0.5- 2mg BID monotherapy in patients <70 with tremor as predominant problem, or advanced PD with persistent tremor despite levodopa or DA use cautiously in elderly D/C gradually AE: confusion, hallucinations, dry mouth, blurred vision, constipation, urinary retention, tachycardia

Question 49

amantadine

Answer 49

(aka symmetrel, symadine) antiviral agent 200- 300 mg/ day in divided doses advantage: low incidence of S/E S/E: ankle edema, livedo reticularis mechanism of action unknown its a weak/ mild antiparkinsonian drug useful for akinesia and rigidity best as short term monotherapy in mild disease

Question 50

COMT inhibitors (catechol- O- methyl transferase)

Answer 50

Entacapone (comtan) 200mg w/ each dose of Levodopa (max 8/ day) Tolcapone (tasmar) 100mg TID- use as last resort, monitor LFT's these are levodopa extenders, ineffective if used alone mainly used to tx motor fluctuations, end of dose "wearing off" periods increases plasma half- life of levodopa may allow a reduction in the total daily levodopa dose by 30%

Question 51

final thoughts on meds

Answer 51

Levodopa or DA initally Levodopa is the most effective treatment, although carries higher risk of dyskinesias than DA Initiate therapy with a DA in younger patients (<65yo) and levodopa in elderly patients (>65) Anticholinergic drugs- for younger patients with tremor as predominant problem

Question 52

to worry about- advanced PD

Answer 52

as many as 50% of patients on levodopa for 5 yrs experience motor fluctuations and dyskinesia Especially common in patients with younger onset (<50yo) motor function alterations between periods of being "on" = responding to med and being "off" = experiencing symptoms of PD Dyskinesia- abnormal involuntary movements

Question 53

more to worry about w/ advanced PD

Answer 53

as the disease advances, effects of levodopa begins to wear off approx 4 hours after each dose (1/2 life= 90 minutes) so patients will begin to be aware of a wearing "off" effect less than 4 hours after levodopa dose increasing the dose is not usually effective, will increase SE w/o increasing dose duration shorten the dose interval while administering lower doses is usually a more effective approach add COMT inhibitor avoid taking levodopa with high protein meals

Question 54

surgery- deep brain stimulation (DBS)

Answer 54

surgically implanted, battery operated medical device (similar to pacemaker) that delivers electrical stimulation to targeted areas in the brain, blocking the abnormal nerve signals that cause tremor and PD symptoms. consists of: lead (electrode) that is implanted in the brain, extension connects lead to neurostimulator, neurostimulator ("battery pack")- usually implanted under the skin near the collarbone the most frequently performed surgical procedure for the treatment of advanced PD factors predictive of benefit: preoperative levodopa responsiveness