Parkinson’s Disease Flashcards
MOVEMENT DISORDERS (38 cards)
State the Main categories of movement disorders
- Parkinsonism
- slowness of movement/bradykinesia (also a hallmark for diagnosis)
- Tremor (can also be symptom)
- oscillatory rhythmic movements
- Dystonia
- torsional patterned movements
- 2 AND 3 = EXCESS OF MOVEMENT
state Parkinson’s disease criteria (PD)
- INSIDIOUS ONSET, SLOWLY PROGRESSING
- “So slight and nearly imperceptible are the first inroads of this malady, and so extremely slow its progress”
- UNILATERAL ONSET, BILATERAL PROGRESSION
- “Thus assuming one of the hands and arms to be first attacked, the other, at this period becomes similarly affected”
- Motor sumptoms: COMBINATION OF BRADYKINESIA, RIGIDITY AND TREMOR
- “Involuntary tremulous motion, with lessened muscular power, in parts not in action and even when supported; with a propensity to bend the trunk forwards”
- NON-MOTOR SYMPTOMS
- “the Sleep becomes much disturbed…The Bowels, which had been all along torpid, in most cases, demand stimulating medicines”
who came up with PD
By James Parkinson (1817)
name a few Risk factors for PD
-environmental: increased - prior head injury, decreased - tobacco smoking
-genetics: increased - LRRK2, decreased - SNCA
name a Neuropathological hallmark of PD:
alpha-synuclein aggregation
- Neuronal degeneration of dopaminergic neurons in Substancia Nigra pars compacta
- alpha-synuclein in Lewy bodies - cytoplasmic inclusions
- also found in brainstem, cortex
describe Braak staging
- 6 neuropathological stages
- onset in Dorsal Motor X nucleus and olfactory bulb
- Symptomatic phase when reaching stage 4: midbrain
- Diffusion to Neocortex in stage 6
explain the Literature current controversy:
- a-synuclein - protective aggregation?
- Is a-synuclein aggregation causative or epiphenomenon of neurodegeneration?
- Is a-synuclein inhibition of aggregation a correct strategy to slow disease progression?
- Are other protein aggregates involved? i.e. tau, Beta amyloid?
name the main disease mechanisms for PD
-protein degradation
-mitochondrial function
-synaptic and endosomal vesicle and protein recycling
-inflammation and ageing
Cardinal motor signs of PD
-asymmetry of clinical signs
-bradykinesia
-rest tremor
-rigidity
-postural instability
Bradykinesia
- THE CORE FEATURE OF PARKINSONISM
- Bradykinesia = slowness in movements (reduced speed)
- Hypokinesia = small amplitude movements (reduced amplitude)
- Akinesia = absence or poverty of expected spontaneous voluntary movement including slow reaction time (Golbe and Ohman-Strickland, 2007)
> UK BRAIN BANK CRITERIA DEFINITION OF BRADYKINESIA
- Slowness of initiation of voluntary movement with progressive reduction in speed and amplitude of repetitive action = DECREMENT
Rest tremor
- Re-emergent Tremor
- Rest tremor (rolling pill tremor) is highly suggestive of PD
- Rest tremor triggered by mental tasks, walking and movements in other body districts
- Some patients may have postural or action tremor
- Postural tremor occurs after maintaining a posture for a few seconds (re-emergent tremor)
Rigidity
-increased resistance
Postural instability (later on)
can use pull up test to confirm
Gait dysfunction in PD
- LOW Velocity, Cadence, Step length, Arm Swing
- Asymmetry of stride length
- Freezing of gait may occur over disease progression
- Motor blocks when walking: gait initiation, turning, passing through a door
- running easier vs walking slow for PD patients
PD clinical diagnostic criteria
A) Presence of the following cardinal motor signs
- Bradykinesia
- Rest tremor (4-6 Hz): Rolling Pill Tremor
- Rigidity
- Asymmetric Onset
B) Sustained response to Levodopa (medication)
C) Atypical signs exclusions
- Postural instability in the first 3 years
- Early freezing
Early hallucinations and dementia
- Vertical gaze palsy
Marked autonomic system involvement
Secondary causes of parkinsonism (i.e.: neuroleptics, vascular)
Progression of PD: Prodromal phase
-50-55
-RBD
-Hyposmia
-anxiety/depression
-constipation
what is the heterogenous presentation due to?
-disease progression
-disease variability among subtypes
Non-motor features and symptoms
-pain
-hyposmia
-sleep
-GI
-fatigue
-dysautonomia
Factors determining heterogeneity of PD
- Different combination of cardinal signs e.g. tremor dominant or akinetic rigid
- Genotype: presence of a gene variant associated to PD (i.e. GBA mutation
- age of presentation (young-onset vs mid-onset vs late onset)
- Disease course:
- Different severity of motor complications
- Occurrence of axial signs: gait and balance dysfunction, falls
- Occurrence of different non-motor signs:- Sleep impairment
- Autonomic dysfunction
- Pain
- Neuropsychiatric symptoms: anxiety, depression, impulsive-compulsive behaviour, hallucinations, delusions, apathy
- Cognitive impairment and late-stage
PD carriers of a Glucocerebrosidase (GBA) heterozygous variant are more likely to have:
- Akinetic-rigid PD
- Anxiety
- Hallucinations
- Dysautonomia
- Motor and Non-motor fluctuations
- Cognitive impairment
what’s the difference between young and late onset PD?
YOUNG:
-levodopa-induced dyskinesia
-slow motor and cognitive progression
-impulsive-compulsive behaviour
LATE:
-hallucinations
-cognitive impairment
-balance and gait problems
-symptoms poor responsive to L-Dopa
Symptomatic treatment of PD
no disease modifying treatment
-physical exercise - rehabilitation
-medications
-surgery
-infusions - device aided therapies
sites for action of PD action
LEVODOPA; increases dopamines
DOPAMINE AGONISTS: mimic dopamine e.g. pramipexole
ANTICHOLINERGIC AGENTS: trihexyphenidyl
BBB: MAO inhibitor e.g. carbidopa
dopamine agonists
eg. pramipexole D3 >D2
-side effects; sleepiness, leg oedema, impulsive-compulsive behaviour
