Parkinsons Flashcards
2 types of movement disorder categories
hypokinetic and hyperkinetic
> mainly due to affected basal ganglia
Epidemiology
2nd most common neurodegenerative disorder
Prevalence: >40 yr 0,3% population, >65 yr 1% of population, >85 yr 2% of population
Netherlands: ±50.000 PD
patients
M > F
Increase in prevalence
Risk Factors
Increased risk:
Age
Pesticides
Repeated traumatic brain injury
Genetic factors (Monogenic, Polygenic risk)
Decreased risk:
Physical exercise
Mediterranean diet
Coffee
Smoking
What type of movement disorder is parkinsonism
hypokinetic but tremors are hyperkinetic
Clues
long prodromal period characterized by:
loss in sense of smell, illegible handwriting, trouble walking, REM sleep disorder, shoulder pain
MDS-criteria for diagnosis
Step 1: Define parkinsonism
Step 2: Is the parkinsonism
attributable to PD?
Defining parkinsonism
Bradykinesia (Decline in amplitude and frequency, Slowness of movements)
AND
Either rigidity
OR resting tremor (3-6 Hz in resting limb)
What types of rigidity can there be
Lead pipe rigidity:
Constant resistance to motion throughout the entire range of movement
Cogwheel rigidity:
Resistance that stops and starts as the limb is moved through its range of motion
Overview of motor symptoms in PD
Stare, decreased mobility in face
Stooped posture, rigidity, flexed elbows + wrists, reduced arm swinging, trembling extremities, shuffling short-stepped gait
Is the parkinsonism attributable to PD?
Clinically established PD
* Absence of absolute exclusion criteria
* At least two supportive criteria
* Absence of red flags
Clinically probable PD
* Absence of absolute exclusion criteria
* Presence of red flags counterbalanced by supportive criteria (no more than 2 red flags)
PD Exclusion criteria
CLEAR clinical signs for a differential diagnosis:
▪ Cerebellar abnormalities
▪ Downward vertical gaze palsy
▪ Diagnosis of behavioral frontotemporal dementia or primary
progressive aphasia
▪ Lower limb parkinsonism (>3 year)
▪ Drug-induced Parkinsonism
▪ Absence of L-dopa response
▪ Normal presynaptic dopaminergic neuroimaging
▪ Alternative condition
PD Red flags
Clinical clues towards a differential diagnosis:
- Rapid progression of gait impairment (wheelchair < 5 y)
- Complete absence of motor symptom progression (5 y)
- Early bulbar dysfunction (< 5 y) (struggle to swallow)
- Early severe autonomic failure (< 5 y)
- Recurrent falls (> 1/y) within 3 years of onset
- Disproportionate anterocollis or contractures (< 10 y)
- Absence of non-motor symptoms (5 y)
- Pyramidal tract signs
- Symmetric parkinsonism
Diagnostic weighting process
weighing exclusion criteria, red flags, and support criteria to see if it is PD or atypical parkinsonism
Supportive criteria
- Clear good L-dopa response
- Presence of L-dopa dyskinesia Dyskinesia: if you give levodopa, at intermedium dose works perfectly
At peak dose = become hyperkinetic (this is a sign that the medication works perfectly, of course after you lower the dose) - Observed rest tremor of a limb
- Presence of olfactory loss
MRI
In case of clear doubts on differential diagnosis
shows:
vascular damage
cross-bun sign: indicates degeneration of fibers
Hummingbird sign: indicates PSP (downward gaze palsy)
DAT-SPECT
In case of clear doubts on differential diagnosis → drug induced parkinsonism?
used to assess dopaminergic neuron degeneration
uses a radioactive ligand
Abnormal in any process that reduces density of dopamine transporters
Parkinsonism: differential diagnosis
Atypical parkinsonism
- Multiple system atrophy (MSA)
- Progressive supranuclear palsy (PSP)
- Dementia with Lewy Bodies (DLB)
- Cortical basal degeneration (CBD)
Drug induced parkinsonism
Vascular parkinsonism
Pathological hallmarks
Alpha-synuclein
Lewy Bodies and Lewy Neurites
Degeneration of dopaminergic neurons in the substantia nigra
Alpha-synuclein aggregates and forms lewy bodies = degeneration of dopaminergic neurons in the substantia nigra
Possible gut-brain axis involvement
Braak staging
method to describe degree of pathology
Ascending course from peripheral and enteric nervous system → medulla oblongata → midbrain → neocortex
- Stage 1-2: autonomic and olfactory disturbances
- Stage 3-4: sleep and motor disturbances
- Stages 5-6: Emotional and cognitive disturbances
Non-motor symptoms of PD
Neuropsychiatric
- Depression/anxiety
- Cognitive disturbances
- Psychosis / visual hallucinations
- Impulse control disorders
Sleep
- Insomnia
- Restless legs
- REM sleep behavior disorder
- Excessive daytime sleepiness
Autonomic
- Orthostatic hypotension
- Obstipation
- Urine incontinence
- Impotence
Rest
- Olfactory loss
- Pain
- Tiredness
Apart from dopaminergic neurons what other neurons are affected
Noradrenergic
Serotonergic
Cholinergic
Symptomatic timeline
pre-motor period
- non-motor
constipation > RBD > depression
PD diagnosis
Early
- non-motor + motor
Late
- non-motor + motor + complications (e.g psychosis)
Clinical subtypes of parkinsons
Presents heterogeneously
- Tremor-dominant (slower progression, less cognitive decline)
- Akinetic-rigid (faster progression, more non-motor symptoms).
- Diffuse-malignant (rapid decline, cognitive dysfunction)
PD Management
Dopaminergic treatment
Levodopa
Dopamine agonist
MAO-B inhibitor (inhibit breakdown of dopamine)
Advanced therapy
Continuous administration (f.e.
apomorphine or duodopa pomp, reduces fluctuations)
Deep Brain Stimulation
Non-pharmacological
Physiotherapy
Speech and language therapy
Psychology
Palliative care
