Parkinson’s Disease Flashcards
MOVEMENT DISORDERS
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
levodopa induced dyskinesia (LID)
involuntary choric or choreodystonic movements appearing at the peak of levodopa effect
which motor symptoms are mostly due to disease progression
-depression/anxiety
-falls
-freezing of gait
-speech disturbance
-postural abnormalities
-apathy
which motor symptoms are mostly due to interaction of dopaminergic treatment and disease progression
-motor fluctuations
-levodopa-induced dyskinesia
which non-motor symptoms are mostly due to interaction of dopaminergic treatment and disease progression
-non-motor fluctuations
-impulsive-compulsive
-psychosis
-sleep disorders
-cognitive impairement
neuropsychiatric spectrum of PD
-affective disorders; depression, anxiety
-psychosis; illusions and hallucinations, delusions
-impulsive-compulsive behaviours (ICB); impulse control disorders, dopamine dysregulation syndrome, punding
-cognitive disturbances; apathy, mild cognitive impairment, dementia
Impulsive control disorders (ICD):
- Pathological Gambling
- Compulsive Shopping
- Ipersexuality
- Binge Eating
Dopamine Disregulation Syndrome
Compulsive use of dopaminergic medication (i.e. levodopa)
punding
complex prolonged, purposeless, and stereotyped behaviour
Risk factors for ICB
-young age
- Male gender
- Treatment with
- Dopamine-Agonists
Hallucinations
- Minor hallucinations/ Illusions
- Presence Hallucinations
- Passage hallucinations
- Visual Hallucinations
- Auditory Hallucinations (rare)
- Hallucinations are triggered by
Parkinson’s medications. - Acute onset of hallucinations often occur in the context of urinary tract infections or any other systemic diseases
COGNITIVE IMPAIRMENT AND DEMENTIA
- Cognitive Disturbances in 40% of PD (Cummings, 1988)
- The full spectrum of cognitive impairment, from subjective cognitive decline to dementia, has been observed in Parkinson disease
- Mild cognitive impairment in PD usually progresses to dementia, but can be stable and even revert in some patients
- Time to dementia after PD diagnosis was approximately 10 years
- Risk factors for dementia in Parkinson by a recent meta-analysis:
- Older age o Higher motor severity
- Hallucinations
- REM sleep behavior disorder
- Smoking
- Hypertension
- Low educational level
Novel treatments
- deep brain stimulation
- levodopa duodenal infusion
- apomorphine infusion
- device aided therapies for advanced PD (about 10-20% of patients are eligible)
- Commercialized devices and stimulating parameters for DBS
- Amplitude (Volt)
- Pulse width (mcsec)
- Frequency (Hz)
- Active contact:
- monopolar (case anode)
- bipolar (case off)
- Advanced programming
deep brain stimulation
- uses electrical stimulation of deep brain structure to treat movement disorders
- brain pacemaker
- where to stimulate?
- Ventralis Intermedius thalamic nucleus (VIM): effective on tremor
- Globus Pallidus pars interna (Gpi):
Effective for dykinesia > bradykinesia - Nucleo Subtalamico: effective for tremor, bradykinesia, rigidity, non-motor symptoms
summarise PD
- Parkinson’s disease is a complex disease, more frequent in older people but it may affect also young people
- Parkinson’s disease is not only a motor disorders but there is prominent neuropsychiatric involvement as well as presence of many other non-motor symptoms
- Symptomatic treatment of PD is achieved with a combination of oral medication.
- Levodopa remains the most effective medication for PD and is combined to IMAOB, ICOMT or dopamine agonists.
- Device aided therapies can improve quality of life is patients
- Physical exercise is a symptomatic treatment for PD
