435 - Parkinson's Disease Flashcards
What is the classical features of Parkinson’s disease?
Cardinal Features - actually occurs midstage
(M: TRAP)
- Tremor (resting) (3-5Hz)
- Rigidity (stiffness)
- Akinesia/bradykinesia
- Postural instability, gait dysfunction
__________
Additional Features - Freezing of gait
- Speech difficulty
- Swallowing impairment
__________
Non-motor Features - actually occurs earlier but missed - Autonomic disturbance
- Sensory alterations
- Mood disorders
- Sleep dysfunction
- Cognitive impairment
- Dementia
What are the pathological hallmark features and neuropathophysiologic changes in PD?
- Accumulation of abnormally folded proteins in neurons
- Defective antioxidant systm, increased ROS
- Formation of Lewy bodies, alpha synuclein in neurons
- Braak theory of spread: ANS -> brainstem -> cortex - Neuronal degeneration
A. Non-dopaminergic degeneration (non-motor features)
- Cholinergic neurons of nucleus basalis of Meynert
- Noradrenaline neurons of locus coeruleus
- Serotonin neurons of raphe nuclei in brainstem
- Olfactory system neurons
- Cerebral hemispheres, spinal cord, peripheral autonomic nervous system
B. Dopaminergic neuron degeneration in subtantia nigra (motor features)
- Dopamine depletion in striatum -> imbalance in striatal activity
> Hypoactivity of striatonigral (direct) pathway
> Hyperactivity of striadopallidal (indirect) pathway
–> Disinhibition of STN, increased activity of GP/SN neurons resulting in inhibition of thalamic ventral tier nuclei
(thalamic nuclei activates cortical areas that generate movement)
–> Poverty and slowness in movements
Describe the natural course of PD
Braak Theory of Staging (of Lewy Body Dementia)
**Early Stage - Non-motor symptoms**
Begins in peripheral ANS, olfactory, dorsal motor nucleus of vagus nerve, spreads in preductable manner to SN, cerebral hemispheres
- Constipation
- Anosmia
- REM sleep disorder
- Cardiac denervation
Midstage - cardinal motor features
Affects SN, basal nucleus of Meynert
Endstage - higher function and cognitive impairment
Affects cortex
What are the causes of Parkinsonism?
- Idiopathic Parkinsonism
- Parkinsonism-Plus Syndromes
- Secondary Parkinsonism
- Neurodegenerative disorders
What are the idiopathic and Parkinsonism Plus Syndomes?
Idiopathic PD
- Sporadic
- Genetic
Parkinsonism-Plus Syndrome
- Lewy Body Dementia
- Progressive supranuclear palsy (PSP): Parkinsonism, Richardson variants
- Corticobasal degeneration
- Frontotemporal dementia
- Multiple system atrophy (MSA): cerebellar, Parkinson types
What are the secondary causes of Parkinsonism?
- Drug induced
- Dopamine receptor blockers: neuroleptics, antiemetics (metoclopramide)
- Dopamine depleters: reserpine, tetrabenazine
- CCB: flunarizine, cinnarizine, diltiazem
- Lithium
- Methyldopa - Toxins
- Carbon monoxide, carbon disulfide
- Methanol, ethanol, hexanes
- Manganese
- Cyanide
- Disulfiram
- MPTP - Hydrocephalus - NPH, non-communicating
- Trauma
- Tumour
- Metabolic
- Hypoxia
- Liver failure (hepatocerebral degeneration)
- Hypocalcaemic Parkinsonism - Infection
- Postencephalitic parkinsonism
- AIDS
- Intracytoplasmic hyaline inclusion disease
- CJD
- Subacute sclerosing panencephalitis (SSPE) - Vascular and vasculitis
- Multi-infarcts
- Binswanger’s disease
- Lower body parkinsonism
What neurodegenerative disorders are associated with parkinsonism?
- Wilson’s disease
- Huntington’s disease
- Haemochromatosis - neurodegeneration with brain iron accumulation
- SCA type 3
- Fragile X associated ataxia-tremor-parkinsonism
- Prion diseases
- X-linked dystonia-parkinsonism
- Gertsmann-Strausler-Scheinker disease
- Neuroacanthocytosis
What is the mean onset of PD?
What is the lifetime risk of general population to develop PD?
Mean onset is 60 years old
Lifetime risk: ~3% men; 2% women
Gene mutation - may develop at younger age
What are the clinical hallmarks of PD?
Onset: 60 years old
Site: unilateral, asymmetrical
Clinical types:
1. Tremor-dominant
- Earlier age of onset, slower progression, preserved cognition
- Often co-exist with essential tremor
- Postural instability and gait difficulty
- More bradykinesia, more rapid progression, demenatia
What is Parkinsonism?
Syndrome manifest by bradykinesia, rigidity and/or tremors
Diagnosis of Parkinson’s Disease:
Movement Disorder Society (MDS) Clinical Diagnostic Criteria for Parkinson’s Disease
Diagnosis of clinically established PD:
A. Diagnostic criteria
B. At least 2 supportive criteria
C. Absence of absolute exclusion criteria
D. No red flags
Probable PD:
A. Absence of absolute exclusion criteria
B. Red flags counterbalanced by supportive criteria (1 to 1, with no more than 2 red flags)
__________________________
Diagnostic Criteria
1. Bradykinesia (compulsory)
2. Muscular rigidity, and/or
3. Resting tremor 3-5 Hz (or 4-6 Hz)
Supportive Criteria
1. Clear, dramatic beneficial response to dopaminergic therapy
2. Levodopa induced dyskinesia
3. Past or current rest tremor
4. Olfactory loss or cardiac sympathetic denervation on MIBG scintigraphy
Absolute Exclusion Criteria
1. Unequivocal cerebellar abnormalities
2. Downward vertical supranuclear gaze palsy or selective slowing of downward vertical saccades
3. Diagnosis of FTD or primary progressive aphasia within first 5 years of disease
4. Features restricted to lower limbs > 3 years
5. Dose and time-course consistent with drug-induced
6. No observable response to high dose levodopa despite at least moderate severity
7. Unequivocal cortical sensory loss
8. Normal functional neuroimaging of presynaptic dopaminergic system
9. Documented alternative condition known to produce Parkinsonism
Red Flags
1. Rapid progression of gait impairment requiring WC within 5 years onset
2. Absent progression of motor symptoms/signs over 5 years, unless related to treatment
3. Early bulbar dysfunction
4. Inspiratory dysfunction - diurnal or nocturnal respiratory stridor or frequent inspiratory sighs
5. Severe autonomic failure first 5 years onset
6. Recurrent > 1/year falls because of impaired balance within 3 years onset
7. Disproportionate anterocollis (dystonic) or contractures of hands or feet within first 10 years
8. Absent of non-motor features - > sleep dysfunction, autonomic dysfunction, psychiatric dysfunction
9. Unexplained pyramidal tract signs
10. Bilateral symmetric parkinsonism
