Parkinsons + Parkinsonism Flashcards
What are the 3 main groups of movement disorder?
- Pyramidal
- Hyperkinetic
- Hypokinetic
What 2 movement problems are pyramidal?
- Pyramidal weakness
* Spasticity
Name the 5 main hyperkinetic movement disorders.
- Distonia
- Tics
- Myoclonus
- Chorea
- Tremor
Name the 3 main hypokinetic movement disorders.
- Rigidity
- Bradykinesia
- Parkinsons
Extrapyramidal movement disorders can be either ___________ or __________
- Hyperkinetic
* Hypokinetic
What area of the brain do extrapyramidal movement disorders involve?
Basal ganglia
What are of the brain does pyramidal movement disorders involve?
Corticospinal or pyramidal tract
What 3 things does a ‘parkinsonian’ syndrome refer to?
- Rigidity
- Akinesia/bradykinesia
- Resting tremor
What is dystonia?
Prolonged muscle spasms and abnormal postures.
What is chorea-ballismus?
Fragments of movements flow irregularly from one body segment to another, causing a dance-like appearance.
When can the term ballismus be used?
Amplitude of movements is large
What is the basal ganglia?
A collection of grey matter with important connections to many other parts of brain
What is the basal ganglia important for?
Movement co-ordination
What motor features does PD present with?
Tremor, muscular rigidity, akinesia, rest tremor, gait and postural impairment.
Motor features in PD are heterogenous
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There are 2 main groups of motor symptoms in PD. Name these.
Tremor dominant PD – with relative absence of other motor sx
Non-tremor dominant PD – such as akinetic-rigid syndrome and postural instability gait disorder.
Also, mixed/intermediate phenotype
There course and prognosis of the 2 types of PD motor symptoms are different
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What is the progression and course like of the ‘tremor dominant PD’?
Slower rate of progression and less functional disability.
What do the non-motor features of PD include?
- Olfactory dysfunction.
- Cognitive impairment.
- Psychiatric sx.
- Sleep disorders.
- Autonomic dysfunction.
- Pain.
- Fatigue.
Non-motor sx are common in early PD (as well as before the onset of motor features), and are associated with reduced health-related quality of life.
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When do the non-motor symptoms of PD usually present?
Before the onset of the motor symptoms
List the main motor features of PD.
- Tremor
- Bradykinesia
- Rigidity
- Postural instability
List some non motor features of PD that patients might present with.
Sleep disorders, hallucinations, GI dysfunction, depression, cognitive impairment/dementia, anosmia.
When can a resting tremor be seen?
When the pt is sitting with their hands on their lap
Cog-wheel rigidity is characteristic of PD
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Describe pin rolling.
This is another characteristic tremor seen in PD - basically imagine someone rolling a pin between their thumb and index finger (pronation and supination)
When is PD usually diagnosed?
When motor symptoms onset
Non-motor symptoms can be present for more than a ______ before onset of motor symptoms
Decade
The pathogenic process that causes PD is presumed to be underway during what? What does this involve?
- The premotor phase.
Involves the regions of the peripheral and central nervous system, in addition to the dopaminergic neurones in the SNpc (Substantia Nigra Pars Compacta)
What is the progression of PD characterised by?
Worsening motor features, which initially respond well to symptomatic therapies (‘honeymoon phase’).
What are the advance stages of PD characterised by?
The emergence of complications related to long term symptomatic treatment, including motor and non-motor fluctuations, dyskinesia and psychosis.
In late-stage PD treatment, resistant motor and non-motor features are prominent. What do these include?
Axial motor symptoms …
- Postural instability
- Freezing of gait
- Falls
- Dysphagia
- Speech dysfunction
Dementia occurs in __ % of PD patents
83%
What kind of sleep disorder to people with PD get?
REM sleep behaviour disorder
What is a REM sleep behaviour disorder?
Parasomnia - abnormal and disruptive behaviour during sleep
What kind of odd sleep behaviours is seen in someone with PD?
- Talking
- Laughing
- Shouting
- Gesturing
- Grabbing
- Punching
- Kicking
- Sitting up in bed
Dreams are ________ during REM sleep disorders in PD patients
Enhanced
The disordered sleep behaviours that people with PD have is during REM sleep
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How is REM sleep behaviour disorder in PD patients treated?
Clonazepam / Melatonin at bedtime
How is REM sleep behaviour disorder in PD patients diagnosed?
Overnight polysomnography
What is the ICD criteria for the diagnosis of REM sleep behaviour disorder in PD patients?
Overnight polysomnography to document ….
- REM without atonia (such as sustained or intermittent muscle activity measured by electromyogram)
- Rule out mimics (ie. obstructive sleep apnoea, non-rapid eye movement parasomnia, seizures).
PD pts with RBD tend to have a disease subtype characterized by more severe autonomic dysfunction, gait impairment and dementia
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Outline the criteria for the diagnosis of PD.
Bradykinesia + 1 or more of the following:
- Muscular rigidity
- 4-6 Hz rest tremor
- Postural instability
What is the pathology of PD?
Loss of dopaminergic neurones within the SNpc and Lewy body pathology
List areas of neuronal loss in PD (except for the substantial nigra).
- Locus ceruleus
- Nucleus basalis Meynert
- Pedunculopontine and raphe nuclei
- Dorsal motor nucleus of vagus
- Amygdala
- Hypothalamus
Outline the lewy body pathology of PD.
*Mis-folded alpha-synuclei – which is insoluble and aggregated – forms intracellular inclusions (LEWY BODIES) and processes (LEWY NEURITES) of neurones.
Lewy body pathology is not just seen in the brain in PD, where else is it seen?
- Spinal cord
* PNS
What would a section through the brainstem of someone with PD show?
Loss of the normallys dark black pigment in the substantia nigra and locus coeruleus
What does pigment loss of the substantial nigra in PD really show?
Dopaminergic cell loss
Name a neurohistological hallmark of PD
Lewy bodies
What is the greatest risk factor for PD?
AGE !!!
What is the male : female ratio in PD?
3:2
What does an early onset of PD (<40 years) usually indicate?
A genetic cause
In what countries is prevalence of PD higher/lower?
Prevalence is higher in Europe, North America and South America, compared to African, Asian and Arabic countries
PD is the 2nd most common neurodegenerative disorder after Alzheimer’s.
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What is the most common neurodegenerative disorder?
Alzheimers
What was the first gene to be associated with inherited PD?
SNCA, which encodes the protein α-synuclein
What is the most common gene to cause of dominant PD?
LRRK2.
What is the most common genetic cause of recessive PD?
Parkin.
What is the greatest genetic risk factor for PD?
Mutations in GBA.
What does GBA encode?
β-‐ glucocerebrosidase
The lysosomal enzyme deficient in Gaucher’s disease
List some environmental risk factors for developing PD.
- Beta blockers
- Pesticides
- Prior head injury
- Rural living
- Agricultural occupation
List some factors that decrease your risk of having PD.
- Smoking
- Coffee
- NSAID
- Alcohol
- Ca channel blocker
There are no neuroprotective or disease modifying drugs for PD
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What do symptomatic treatments of PD do?
Enhance intracerebral dopamine concentrations
OR
Stimulate dopamine receptors
What is the treatment of PD?
Levodopa
What drugs can be used in the tx of PD?
- Levodopa
- Dopamine agonists
- Monoamine oxydase type B inhibitors
- Amantadine (less common)
When should treatment for PD be started?
When symptoms cause disability or discomfort, aiming to improve fn and quality of life.
Early in the disease, what do bradykinesia and rigidity respond reliably to?
Dopaminergic treatment
What tx is needed for more severe symptoms in PD?
Levodopa and dopamine agonists
MAO B inhibitors are only mildly affective in PD.
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What is tremor inconsistently responsive to?
Dopamine replacement therapy, especially in lower doses.
What drugs are used in the treatment of a tremor in PD?
Anticholinergic agents:
- Trihexyphenidyl
- Clozapine
What side effects are dopamine agonists and levodopa associated with?
- Nausea
- Daytime somnolence
- Oedema (more so in dopamine agonists)
What kind of disorders can people on Dopamine agonists get?
Impulse control disorders
Give examples of impulse control disorders.
- Pathological gambling
- Hypersexuality
- Binge eating
- Compulsive spending
Who should you not give dopamine agonists to?
- Patients with a history of addiction
- OCD
- Impulsive personality
- Elderly, especially those with cognitive impairment
Why should dopamine agonists not be given to elderly people, especially those with cognitive impairment?
Due to their association with hallucinations
Why is Levodopa the best tx for PD?
Provides the greatest symptomatic benefit
What is the major disadvantage of Levodopa?
Long-term use is associated with motor complications …
- Dyskinesia
- Motor fluctuations
What are the motor fluctuations associated with long term use of Levodopa in PD?
Alterations between periods of good motor symptoms control (on time) and periods of reduced motor symptom control (off time).
What are non-motor fluctuations associated with long term use of Levodopa in PD?
Alterations between periods of good non-motor symptom control and periods of reduced non-motor symptom control
What is dyskinesia?
Involuntary choreiform or dystonic movements.
When does dyskinesia in PD mostly occur?
When levodopa concentrations are at their maximum (peak dose).
Less commonly in PD, when might dyskinesia develop?
At the beginning, or end of a levodopa dose (diphasic dyskinesia).
Describe the drug induced psychosis seen in those with PD on Levodopa.
Hallucinations which include minor phenomena, such as the sense of presence or passage hallucinations.
Also well-formed visual – and less commonly non-visual (tactile, auditory, olfactory) – hallucinations. Other psychotic features include illusions and delusions, often with paranoia.
People with PD that have been on Levodopa for a long term can develop a drug induced psychosis
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What causes the dyskinesia and motor fluctuations in someone on Levodopa?
The pulsatile stimulation of striatal dopamine receptors in later disease stages
What is the management to reduce dopamine fluctuations?
- A dopamine agonist.
- Monoamine oxidase type B inhibitor (MOA B inhibitor).
- Catechol- O – methyltransferase inhibitor (COMT inhibitor).
List the dopamine agonist drug formulations.
- Long-acting oral levodopa formulations are being developed.
- Direct delivery of a stable levodopa-carbidopa gel (‘Duodopa’) into the duodenum via percutaneous endogastric gastrostomy tube, attached to a portable infusion pump.
- Subcutaneous infusion of the potent dopamine agonist apomorphine.
- Non-dopaminergic treatments such as amantadine and clozapine can be helpful.
What is psychosis in PD most effectively managed with?
Clozapine
If someone with PD can’t take Clozapine, what is the alternative?
Quetiapine – all other neuroleptics should be avoided though
What risks are there with Clozapine?
- Idiosyncratic adverse drug reactions.
* Agranulocytosis.
Give an example of a cholinesterase inhibitor.
Rivastigmine
In patients with PD and dementia, who have visual hallucinations and delusions, what can be prescribed?
Rivastigmine
What is last stage dementia in PD treated with?
Rivastigmine
What surgical treatments can be used for the treatment of motor sx/complications? What do these target?
- Deep brain stimulation.
* Target either the subthalamic nucleus or globus pallidus internus.
What is Primavanserin?
Selective serotonin 5-HT@A inverse agonist
What can Primavanserin be used to reduce symptoms of in PD?
Positive psychotic symptoms, without worsening of motor function
Depression associated with PD is treated with antidepressants
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