Parkinson's and Movement Disorders Flashcards
What are basal ganglia?
Deep set nuclear structures = involved in initiation of movement and modulation of movement
How do basal ganglia interact with the cerebral cortex?
Receive input from cerebral cortex, process it and relay back to the cerebral cortex via the thalamus
What can basal ganglia disease lead to?
Hypokinetic or hyperkinetic movement disorders
What are features of movement disorders affecting the corticospinal/pyramidal tracts?
UMN features = pyramidal weakness, spasitcity
What are some features of movement disorders affecting the basal ganglia?
Hypokinetic = rigidity, bradykinesia, Parkinsonism Hyperkinetic = ticks, dystonia, myoclonus, weakness, spasticity
What do movement disorders affecting the cerebellum present with?
Ataxia
What is the inheritance of Parkinson’s disease?
95% idiopathic and 5% familial
What are the pathological hallmarks of Parkinson’s disease?
Sections through brainstem reveal loss of normally dark black pigment in the substantia nigra and locus coeruleus
What does pigment loss correspond to?
Dopaminergic neuron loss = need reduction of 50-60% for symptoms to become clinically apparent
What is the relevance of Lewy bodies in Parkinson’s disease?
Non-specific hallmark = marker of poor neuron health, not present in some genetic PD
What are the motor symptoms of Parkinson’s disease?
Tremor, bradykinesia, rigidity, postural instability
What are the non-motor symptoms of Parkinson’s disease?
Sleep disorders, hallucinations, GI dysfunction, depression, cognitive impairment/dementia, anosmia
Where are dopaminergic neurons lost from?
The pars compacta region of the substantia nigra
What is Braak’s staging used for?
Helps explain the non-motor symptoms of Parkinson’s disease = first abnormalities are in olfactory bulb
What are the subtypes of motor features in Parkinson’s disease?
Features are heterogenous = tremor dominant, non-tremor dominant, mixed/indeterminate phenotype
What are some features of tremor dominant Parkinson’s disease?
Associated with slower rate of progression and less functional disability = relative absence of other motor symptoms
What are some examples of non-tremor dominant Parkinson’s disease?
Akinetic-rigid syndrome and postural instability gait disorder
What are some features that support a diagnosis of Parkinson’s disease?
Unilateral onset of bradykinesia and at least one of resting tremor, rigidity or postural instability
What are some additional motor features that may support diagnosis of Parkinson’s disease?
Stooped fixed posture, dystonic posture, hypomimia, shuffling short stepped gait
What are some additional non-motor features that may aid a diagnosis of Parkinson’s disease?
Late onset hyposmia, depression and anxiety, constipation, bladder problems, pain, subtle mental impairment
What kind of rigidity occurs in Parkinson’s disease?
Lead pipe = constant resistance throughout passive movement
Cog wheel = superimposed clicking resistance which is attributed to underlying tremor
What symptoms would patients with Parkinson’s disease be unlikely to present with?
Early onset bulbar problems, dementia, prominent eye movement disorder, intrusive early autonomic problems
What is the epidemiology of Parkinson’s disease?
More common with advancing age and in men
Risk factors = older age, positive family history, male
What would indicate a genetic cause of Parkinson’s disease?
Onset age <40
What mutations are implicated in Parkinson’s disease?
LRRK2 = most relevant autosomal dominant mutation PARKIN = most relevant autosomal recessive mutation
What treatment do bradykinesia and rigidity respond to?
Dopaminergic treatment
What is used to treat severe Parkinson’s disease symptoms?
Levodopa and dopamine agonists
What drug class is used to treat tremors?
Anticholinergics = trihexyphenidyl or clozapine
What are some features of dopamine agonists?
Associated with impulse control disorders
Avoid in history of addiction, OCD or impulsive personality
Don’t prescribe in elderly (especially with cognitive impairment) = cause hallucinations
What side effects are dopamine and levodopa associated with?
Nausea, daytime somnolence and oedema
What is longterm levodopa use associated with?
Dyskinesia and motor fluctuations
What are the longterm complications of dopaminergic agonists?
Motor and non-motor fluctuations, dyskinesia, drug induced psychosis
What are the first line agents for treating Parkinson’s disease?
Dopamine agonists, levodopa, MAO inhibitor
What are add on medications for treating Parkinson’s disease?
Catechol-O-methyltransferase inhibitor, MAO inhibitor, dopamine agonists, apomorphine
What does the Parkinson’s MDT consist of?
PD specialist nurses, physiotherapists, pharmacists, occupational therapists, movement disorder specialists, GPs
What are some non-oral therapies for treating Parkinson’s disease?
Deep brain stimulation, DNODOPA, continuous apomorphine infusion
What is bradykinesia?
Slowness of movement with progressive loss of amplitude/speed during attempted rapid alternating movement of body segments
How do you assess bradykinesia?
Ask patient to perform some repetitive movements as quickly and widely as possible or getting patient to stand
What are some associated features of bradykinesia?
Hypomimia, hypophonia and micrographia
What is a Parkinsonian tremor?
Rhythmic involuntary oscillatory movement of affected body part = usually pill-rolling type tremor
What are some features of a Parkinsonian tremor?
Low-mid range frequency (3-6Hz) with variable amplitude
Vanishes with active movement
Reappears when arms held outstretched
When is a Parkinsonian tremor best observed?
When patient is focused on a particular task
What is rigidity?
Increased muscle tone felt during examination by passive movement
What are some features of rigidity?
Resistance felt throughout full ROM = no increase with higher mobilising speed
What manoeuvre confirms the presence of rigidity?
Froment’s manoeuvre = rigidity increases in examined body segment by voluntary movement of other body parts
What is the typical posture of a patient with Parkinson’s disease?
Stooped posture = due to impaired postural reflexes, may have extreme anterior truncal flexion (camptocornia)
What kind of gait do patients with Parkinson’s disease have?
Slow, narrow base with short shuffling steps, decreased arm movement
What is festination?
Very fast succession of steps and difficulty stopping
What investigations can be done for Parkinson’s disease?
Structural brain imaging and genetic testing
Dopamine functional imaging
Positive levodopa challenge
What are some examples of dopamine functional imaging techniques?
PET with fluoro-dopa = less common
Dopamine transporter imaging with single photon emission CT (DAT-SPECT)
What are some red flags for Parkinson’s disease?
Symmetrical symptoms and fast disease progression
Frequent falls and marked autonomic dysfunction
Severe axial/lower limb involvement and apraxia
Eye movement disorder and bulbar features
Other unexplained movement disorder
Pyramidal/cerebellar dysfunction
Parietal associative sensory disturbances
Severe cognitive deterioration or psychosis
Negative levodopa challenge
What are the differentials of Parkinson’s disease?
Vascular and drug induced Parkinsonism Essential tremor Multisystem atrophy Progressive supranuclear palsy Fragile X-tremor ataxia syndrome (FXTAS)
What are some features of vascular Parkinsonism?
Predominantly lower limbs = spasticity, hemiparesis, pseuobulbar palsy
Rest tremor uncommon and poor levodopa response
Structural brain imaging guides diagnosis
What are some features of drug induced Parkinsonism?
Symmetrical = coarse postural tremor, tardive dystonia, orolingual dyskinesia, akathsia
Symptoms emerge after drug introduction and resolve after its withdrawl
What are some features of an essential tremor?
Symmetric postural or kinetic tremor with higher frequency = infrequently observed at rest
Autosomal dominant and age of onset about 15
Mild head tremor and shows alcohol responsiveness
What is multisystem atrophy?
Common cause of degenerative Parkinsonism = age of onset 60-70
Core triad of dysautonomia, cerebellar features and Parkinsonism
What are some features of multisystem atrophy?
Jerky postural tremor, generalised hyperreflexia and extensor plantar responses, severe dysarthia/dysphonia, marked antecollis, inspiratory sighing, orofacial dystonia
What does an MRI of a patient with multisystem atrophy show?
Cerebellar and pontine atrophy = hot cross bun sign
What is progressive supranuclear palsy?
Symmetric akinetic-rigid syndrome with predominantly axial involvement = gait/balance impairment, retrocollis, pseudobulbar symptoms
What are some features of progressive supranuclear palsy?
Continuous activity of frontalis muscle with eyes wide open and vertical gaze supranuclear palsy
Frontal-subcortical cognitive deficits
No response to levodopa
Potentially Parkinsonism
What is fragile x-tremor ataxia syndrome?
Late onset (age >50) disorder in patients with an abnormal number of CGG repeats in FMR1 gene in premutation range (55-200)
What are some symptoms of fragile x-tremor ataxia syndrome?
Slow disease progression = cerebellar gait ataxia, postural or intention tremor, Parkinsonisms, dysautonomia, cognitive decline, peripheral neuropathy
What are are the symptoms of fragile x-tremor ataxia syndrome in females with premutation?
X-linked inheritance so milder symptoms = premature ovarian failure and menopause
How is fragile x-tremor ataxia syndrome diagnosed?
MRI = T2 hyperintensities in middle cerebellar peduncles
Molecular testing
What may condition may children of fragile x-tremor ataxia syndrome develop?
Classical fragile x syndrome
