Parkinson's Disease and Parkinsonism Flashcards
What are the pyramidal movement disorders?
Pyramidal weakness
Spasticity
What are the extrapyramidal hyperkinetic movement disorders?
Dystonia Tics Myoclonus Chorea Tremor
What are the extrapyramidal hypokinetic (rigidity, bradykinesia) movement disorders?
Parkinsonism
Parkinson’s disease
What are the cerebellar movement disorders?
Ataxia
What is Parkinsonian syndrome?
Rigidity, akinesia/bradykinesia and resting tremor
What is dystonia?
Prolonged muscle spasms and abnormal postures
What is chorea and ballismus?
Fragments of movements flow irregularly from one body segment to another causing a dance-like appearance
Ballismus: if amplitude of these movements is large
What makes up the basal ganglia?
Caudate nucleus, putamen, globus pallidus externa and interna, subthalamic nucleus, substantia nigra
What does PD present with?
Tremor, muscular rigidity akinesia, rest tremor, gait and postural impairment
What are the subtypes of PD?
Tremor dominant PD (relative absence of other motor symptoms)
Non-tremor dominant PD (such as akinetic-rigid syndrome and postural instability gait disorder)
Mixed/intermediate pheynotype
With what subtype is the course and prognosis associated with a slower rate of progression and less functional disability?
Tremor-dominant
What are some non-motor features of PD?
Olfactory dysfunction, cognitive impairment, psychiatric symptoms, sleep disorders, autonomic dysfunction, pain and fatigue
When do non-motor symptoms of PD commonly present?
In early PD, or before the onset of motor features
What is the progression of PD characterised by?
Worsening motor features, which initially respond well to symptomatic therapies (Honeymoon phase)
What are the advanced stages of PD characterised by?
The emergency of complications related to long term symptomatic treatment, including motor and non-motor fluctuations, dyskinesia and psychosis. Treatment resistant motor and non-motor features are prominent and include axial motor symptoms such as postural instability, freezing of gait, falls, dysphagia and speech dysfunction
What is rapid eye movement sleep behaviour disorder?
A parasomnia characterised by abnormal or disruptive behaviours (such as talking, laughing, shouting, gesturing, grabbing, punching, kicking, sitting up in bed) which occurs during REM sleep and are often related to dream enactment
How is RBD diagnosed?
Overnight polysomnography to document the presence of REM sleep without atonia (such as sustained or intermittent muscle activity measured by EMG) and to rule out mimics (such as OSA, non-REM parasomnia, seizures)
What is the treatment for RBD?
Clonazepam or melatonin at bedtime
What are the pathological hallmarks of PD?
Loss of dopaminergic neurons within the SNpc and Lewy body pathology
Where does neuronal loss in PD occur other than the SNpc?
Locus ceruleus, nucleus basalis Meynert, pedunculopontine and raphe nuclei, dorsal motor nucleus of vagus, amygdala, hypothalamus
What is Lewy body pathology?
Misfolded alpha-synuclein, which is insoluble and aggregated, forms intracellular inclusions (Lewy bodies) and processes (Lewy neurites) of neurones. Present in brain, spinal cord and PNS
What gross colour change can be seen in PD?
Loss of the normally dark black pigment in the substantia nigra and locus coeruleus. Pigment loss correlates with dopaminergic cell loss
What is Braak staging used for?
Staging of Lewy body pathology
What is the M:F ratio of PD?
3:2
What is the greatest RF in PD?
Age
What are the most common causes of dominant and recessive PD?
Mutations in LRRK2 and parkin, respectively
What is the greatest genetic risk factor for PD?
Mutations in GBA, which encodes B-glucocerebrosidase, the lysosomal enzyme deficient in Gaucher’s disease
What was the first gene to be associated with PD?
SNCA, which encodes the protein a-synuclein
What are some environmental factors which increase the risk for PD?
Pesticide exposure Prior head injury Rural living Beta blocker use Agricultural occupation Well water drinking
What are some environmental factors which decrease the risk for PD?
Tobacco smoking Coffee drinking NSAID use CCB use Alcohol consumption
What treatment is available for PD?
Symptomatic only- enhance intracerebral dopamine concentrations or stimulate dopamine receptors. Include levodopa, dopamine agonists, monoamine oxidase type B inhibitors, and amantadine
What agents can be effective for tremor?
Anticholinergics, trihexyphenidyl or clozapine
When would levodopa and dopamine agonists be used?
More severe symptoms
What adverse reactions are dopamine agonists and levodopa associated with?
Nausea, daytime somnolence and oedema
What psychological/neurological adverse reactions occur with dopamine agonists?
Impulse control disorders, hypersexuality, binge eating, compulsive spending, hallucinations (so avoid in elderly)
What is levodopa long term sued associated with?
Motor complications (dyskinesia and motor fluctuations)
What are some long term complications of dopaminergic therapies for PD?
Motor fluctuations, non-motor fluctuations, dyskinesia, drug induced psychosis
What are motor fluctuations thought to result from in later disease stages?
The pulsatile stimulation of striatal dopamine receptors
What are some pharmacological strategies to reduce dopamine fluctuations?
A dopamine agonist
MAO B inhibitor
COMT inhibitor
What are some options for the management of complications of long term dopaminergic therapies?
Direct delivery of stable levodopa-carbidopa gel (duodopa) into duodenum via percutaneous endogastric gastrostomy tube attached to portable infusion pump
Subcut infusion of potent dopamine agonist, apomorphine
Non-dopaminergic treatments such as amantadine and clozapine can be helpful
How is psychosis in PD managed?
Clozapine (be aware of idiosyncratic adverse drug reactions and agranulocytosis)
Quetiapine
What might reduce visual hallucinations and delusions in PD patients with dementia?
Cholinesterase inhibitors, such as rivastigmine
What is depression associated with PD treated with?
Antidepressants: tricyclics preferably, SSRIs, extended release formulation of venlafaxine, a serotonin and norepinephrine reuptake inhibitor and the dopamine agonist pramipexole
What is late stage dementia in PD treated with?
Rivastigmine
What are the motor symptoms of PD?
Bradykinesia
Rest tremor
Rigidity
Postural and gait impairment
What is Bradykinesia?
Slowness of movement with progressive loss of amplitude or speed during attempted raid alternating movement of body segments
What is hypomimia?
Decreased facial expression and eye blinking
What is micographia?
Progressively smaller handwriting
How is a rest tremor described?
Rhythmic oscillatory involuntary movement of affected body part at rest
Vanishes with active movement
At what frequency is a rest tremor?
Low to mid range (3-6Hz) with variable amplitude
Where can the tremor effect people in PD?
Upper limbs, lower limbs, jaw, tongue
Not head
How is rigidity described?
Increased muscle tone felt during examination by passive movement
Resistance felt throughout full movement
No increase with higher mobilising speed
What is a positive Froment’s manoeuvre?
Rigidity increased in examined body segment by voluntary movement of other body parts
How is postural and gait impairment described?
Stooped posture owing to impaired postural reflexes -in some cases camptocormia
Slow gait, occurs at narrow base with short, shuffling steps
What is festination?
Very fast succession of steps and difficulties stopping
What investigations are required for PD?
Rule out treatable conditions of asthenia (hypothyroidism, anaemia)
Structural brain imaging
Possible dopamine functional imaging: PET with fluoro-dopa, Dopamine transporter imaging with single photon emission (DAT-SPECT)
(Dopamine imaging unable to distinguish PD from other causes of Parkinsonism)
Positive levodopa challenge
Genetic testing
What are some red flags in PD diagnosis?
Absence of asymmetry of symptoms Severe axial or lower limb involvement Frequent falls Fast progression Eye movement disorder Tics, myclonus, chorea Pyramidal/cerebellar dysfunction Bulbar/psuedobulbar features Parietal associative sensory disturances Apraxia Severe cognitive deterioration or psychosis Marked autonomic dysfunction -ve levodopa challenge
What is vascular parkinsonism?
Parkinsonism affects predominantly lower limbs
Rest tremor uncommon
Other signs of brain vascular lesions might be present
Poor levodopa response
Structural brain imaging will guide diagnosis
What will be seen in Drug induced Parkinsonism?
Symmetrical
Course postural tremor
Presence of other drug induced disorders: orolingual dyskinesias, tardive dystonia, akathisia
Series of events is important
Improvement/resolution within few months of complete drug withdrawal
What distinguishes essential tremor with tremulous PD?
Symmetric, postural or kinetic tremor with higher frequency
Infrequent at rest
Often AD inheritance with mean onset of 15y
Alcohol responsiveness
Head tremor- if present, mild
Describe multi system atrophy
Common cause of degenerative Parkinsonism
Age of onset late 6th/7th decades
Core triad of dysautonomia, cerebellar features, and Parkinsonism
What are some features of multi system atrophy?
Jerky postural tremor, pyramidal signs (generalised hyperflexia and extensor plantar responses)
Suboptimal and shortlived levodopa response in 1/3
Dysarthria or dysphonia, marked antecollis inspiratory sighing, orofacial dystonia
What may an MRI show in multi system atrophy?
Cerebellar and pontine atrophy (hot cross bun sign, or hyperintense rim surrounding putamen in T2-weighted sequences)
What is progressive supranuclear palsy?
Symmetric akinetic-rigid syndrome with predominantly axial involvement
What are the features of progressive supranuclear palsy?
Gait and balance impairment (early falls) Tremor infrequent in patients Vertical gaze supranuclear palsy Pseudobulbar symptoms Retrocollis Continuous activity of frontalis muscle with eyes wide open Frontal-subcortical cognitive deficits No levodopa response Some patients may have Parkinsonism
What is fragile X-tremor ataxia syndrome?
Late-‐onset (>50 years) neurodegenerative disorder in pts with an abnormal number of CGG repeats in the FMR1 gene, in the premutation range (55-‐200)
What are the core symptoms of FXTAS?
Core symptoms include cerebellar gait ataxia, postural / intention tremor, variably Parkinsonism, dysautonomia, cognitive decline of frontal type, and peripheral neuropathy
What is the progression in FXTAS?
Slow
What symptoms of FXTAS are seen in females with permutation (x-lined inheritance)?
Milder symptoms, often premature ovarian failure and menopause
What MRI findings are seen in FXTAS?
T2 hyperintensities in the middle cerebellar peduncles (MCP sign)
How is FXTAS confirmed?
Molecular testing
What may children of FXTAS permutation carriers have?
Classical fragile X syndrome
