Parkinson Disease Flashcards
Parkinson Disease
A chronic, progressive neurologic disorder characterized by tremor,
bradykinesia, rigidity, and postural instability.
➢What does this mean to patients?
➢How does this inform the relationship you will have with these
patients?
Pathophysiology
A. Dopaminergic pathways of the basal ganglia–
thalamocortical circuit. Activation of D1 and D2
receptors results in depolarization and
hyperpolarization, respectively, of postsynaptic
neurons.
(Red dots and lines represent excitatory input; black dots
and lines represent inhibitory input)
B. In Parkinson disease, degeneration of presynaptic
nigrostriatal neurons results in inhibition of the
thalamocortical circuit and reduced signaling to the
motor cortex.
(Dashed lines represent reduction of neurotransmitter
activity; GPe, globus pallidus externa; GPi, globus pallidus
interna; SNc, substantia nigra pars compacta; SNr,
substantia nigra pars reticulata; STN, subthalamic nucleus.
Dopamine Receptors
- Different DA tracts throughout the brain
- D1, D5 - dyskinesias
- D2, D3, D4 - improvement in movement
Etiology
- Current hypothesis:
Genetic Factors + Toxin exposure
Parkin gene + Exogenous (e.g. well water, farming, heavy metals)
Alpha-synuclein + Endogenous (e.g. free radicals, infection, iron) - Emerging research:
- Gut microbiome
We know that there’s something probably in the environment, whether it’s something related to farming, well-watered heavy metals, etc. So there’s some kind of genetic predisposition and then some kind of toxin that you’re exposed to that triggers it.
So something like genetic factor like disruption and Alpha-synuclein production. And then something potentially something and exogenous that is triggering a change like free radicals endogenously. Perhaps there’s an infection and there was some theory about iron levels as well. So now there’s emerging research on the gut microbiome.
there’s about 15 different genes involved. But it’s not even consistent from family to family
here’s not a standard for how we investigate or test for different genetic abnormalities because there’s so many
Risk Factors
- Increased risk
- Age: e. But this generally is a disease of middle and older age. It’s very, very rare. Michael J. Fox is one really rare example where the onset is before the age of 40.
- Rural residence, farming, pesticides
- people in rural communities before they were using herbicides or pesticides, like we see in current day. So it’s probably not necessarily our current chemical exposure.
- Frequent consumption of dairy
- higher in rural settings
- Protective factors
- Cigarette smoking
- it seems like nicotine is not the magic ingredient. There’s something else in cigarette smoke
- Coffee, tea, caffeine (dose of 3-5mg/kg)
- Others studied – possibly protective
- Dietary (e.g. vitamin D)
- Hormonal (e.g. sex hormones)
- Vascular (e.g. homocysteine, hypertension)
- Medications (e.g. NSAIDs, statins)
even moderate amounts of chocolate on a regular basis seem to be protective. S
Secondary Parkinsonism
- Drug induced causes
- Dopamine blockers
- antipsychotics
- metoclopramide
- Health Canada warning (July 2011) – TD found mostly in older women after 12 weeks use
- Dopamine depletors
- methyldopa
- reserpine
- Case reports
- Calcium channel blockers
- Antiepileptics (e.g. phenytoin, valproate, levetiracetam)
- Antidepressants (e.g. lithium, MAOIs, SSRIs)
- Chemotherapy (e.g. cystosine, cyclophosphamide, vincristine, adriamycin, doxorubicin, paclitaxel, prednisone)
- Immunosuppressants (e.g. cyclosporine, tacrolimus)
- Medical causes
- Normal pressure hydrocephalus (NPH)
- Infarction
- Infection (e.g. neurosyphylis)
- Trauma
- Any lesion or neoplasm to the substantia nigra
Epidemiology
- Incidence = 20 cases/100 000
- Prevalence = 300 cases/100 000
- Race equal if in same community
- Up to 10% are early onset (before age 40)
- Approximately 10% of LTCF residents
pretty consistent from community to community. So if we compare one rural location, say in Alberta, we compared it to rural India, we compare it to rural England. We’re going to see about the same rate.
Hallmark Features
Resting
tremor
Bradykinesia
Rigidity
Postural
instability
This is a resting tremor. So their arm is supported against gravity, their hands or maybe in their lap, and that’s when the tremor occurs.
The most impairing, the most difficult symptom to live with is actually bradykinesia. = slow movement
We describe this as a cogwheel rigidity. So a patient isn’t just sort of where their arm is stiff. We test this usually by moving someone’s arm up and down. And it kind of goes in a cogwheel way.
Simian posture. So they lean forward and they can have shuffling steps.
Associated Characteristic Problems
Motor symptoms`
* Micrographia
*Masked face
*Decreased blink rate
* Shuffling gait
* Festinating gait
* Microphonia
Autonomic impairment
* Constipation
* Sweating
* Postural hypotension
*Dysphagia
Mental status
*Depression
* Cognitive impairment
*Dementia
We end up seeing Lewy bodies distributed through other parts of the brain as well. And the patient ends up having autonomic damage.
Guidelines - Communication
Guidelines – Diagnosis, Progression
Diagnosis
* C8: diagnosed with MDS Clinical
Diagnostic Criteria
Progression
* C19: Vit E, CoQ10 not neuroprotective: vitamin E and coenzyme Q ten or not neuroprotective. So that is explicitly stated in the guideline because sometimes that’s misrepresented in advertisements or people read that.
* C20: Dopaminergic tx are not neuroprotective: r dopaminergic therapy does not. It’s not disease-modifying, it is just symptomatic.
- Misdiagnosis common
- Diagnositc modalities * *Clinical presentation * Neuroimaging * LD challenge * Olfaction (ancillary)
- No biological markers
so give patients written and verbal communication, engage family and caregivers, not leaving out the patient and all health care providers
There’s debate about levodopa challenge because a variety of movement disorders might respond to a Levodopa challenge. So it’s an even given to a healthy person without a movement disorder, if you get a big dose of levodopa, it’s actually a bit of a stimulant. It can change how you move. And so it’s not recommended in most cases to try that.
Across a number of neurodegenerative conditions, There’s evidenced that olfaction, so how we smell declines quite dramatically. And this can actually be the first. Future might have smelling test
No blood test
Diagnostic
Criteria
(MDS,
Canadian)
Must have:
* Parkinsonism (essential criterion)
* Bradykinesia + at least 1 of tremor or rigidity
* At least 2 supportive criteria
* E.g. olfactory loss, dramatic response to
dopaminergic therapy
M
Must not have:
* Exclusion criteria
* E.g. Restricted to lower limbs, treatment with
dopamine blocker at onset
* No red flags
* E.g. rapid progression, absence of non-motor
features at 5y
- The prognosis for a patient diagnosed in midlife (usual diagnosis age
55-65y) with PD is:
a) 1-2y
b) 5 years
c) 10 years
d) 15 years
e) 20 years
Question
* Most patients with PD will die from which of the following?
a) Bradykinesia
b) Tremor
c) Rigidity
d) Postural instability
e) None of the above
15-20 yrs
- Depends on age at diagnosis
- Complications
Expected mortality approx 15y after onset of complications
none of above
Most patients with Parkinson’s disease don’t die from their Parkinson disease. They actually died from complications like pneumonia. So they become so immobilized later in the disease that they actually can’t function
Guidelines – Motor Symptoms
- General Considerations
- C23-29
- Pharmacologic therapy in early PD
- C30-C41
- Pharmacologic therapy in later PD
- C42-48
- Surgery
- C49-55
- Rehabilitation
- C56-C66
Staging
Hoehn and Yahr Scale is most commonly used scale to measure severity of parkinson symptoms and classifis pt n following stages
. I would not expect you to regurgitate to me what’s in these kind of orange colored boxes. But I do expect you to know that stage one is the earliest, stage five is latest and bedridden. And there’s a progression through that.
earliest stage one, we might not actually use any drug therapy. As we get through the stages. It might help us decide about how aggressive or if we need add-on therapy and research studies have used this staging. So you might look at inclusion criteria. They’re looking at patients stage 1.5 to 2.5. Another study might be only stage three patients
Goals of
Therapy
- Neuroprotection (?) vit E not that beneficial
- Relieve symptoms
- Maximize independence and function
- Prevent injury
- Prevent long-term drug complications
- Overall focus on HRQL
o there’s nothing that we can give patients that says this will protect the rest of your dopaminergic neurons to help you move it still, it seems that we still end up, even with these symptomatic treatments, neurons are continuing to be lost until the patient dies. But we can relieve symptoms.
