Movement disorders Flashcards
The basal ganglia are involved in the _____ of movement and _____ of movement
The basal ganglia are involved in the initiation of movement and modulation of movement
The basal ganglia are a deep set of nuclear structures that receive input from the ________ _____, process it and relay it back to the ______ ____ via the ______
The basal ganglia are a deep set of nuclear structures that receive input from the cerebral cortex, process it and relay it back to the cerebral cortex via the thalamus
Basal ganglia disease can lead to too little (______) or too much (_______) movement disorders
Basal ganglia disease can lead to too little (hypokinetic) or too much (hyperkinetic) movement disorders
What are the pyramidal UMN features of movement disorder?
Pyramidal weakness and spasticity
Describe the presentation of hypokinetic movement disorders?
Dystonia Tics Myoclonus Chorea (Tremor)
Describe the presentation of hyperkinetic movement disorders?
Rigidity, bradykinesia
= Parkinsonism, parkinsons disease
Where do hyperkinetic and hypokinetic movement disorders originate?
The basal ganglia
Where does ataxia originate from?
Cerebellum
What is the neurohistological hallmark of PD?
Lewy bodies
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 Gastrointestinal dysfunction Depression Cognitive impairment/dementia Anosmia
Loss of dopaminergic neurons from the ____ ______ region of the substantial migration- approximately __% loss of neurons (80% depletion in striatal dopamine) gives PD symptoms
Loss of dopaminergic neurons from the pars compacta region of the substantial migration- approximately 60% loss of neurons (80% depletion in striatal dopamine) gives PD symptoms
What are the two subtypes of parkinsons disease?
- Tremor dominant PD (relative absence of other motor symptoms)
- Non-tremor dominant PD (such as akinetic-rigid syndrome and postural instability gait disorder)
- Mixed/indeterminate phenotype
Which sub-type of parkinsons is associated with slower rate of progression and less functional disability?
Tremor dominant
What are the pre-motor/prodromal period symptoms of parkinsons?
Constipation RBD EDS Hyposmia Depression
What are the non-motor symptoms of early stage parkinsons?
Pain
Fatigue
MCI
What are the -motor symptoms of early stage parkinsons?
Bradykinesia
Rigidity
Tremor
What are the complications of parkinsons that occur around 10 years after diagnoses?
Fluctiations
Dyskinesia
What are the late stage complications of parkinsons?
Psychosis
What are the advanced motor symptoms of parkinsons?
Dysphagia
Postural instability
Freezing of gait
Falls
What the the non-motor symptoms of unstable parkinons?
Urinary symptoms
Orthostatic hypotension
Dementia
What is essential Parkinsonism?
Bradykinesia and one (or more) of the following;
- resting tremor
- rigidity (cog-wheel or lead pipe)
- postural instability
What are the additional motor features of parkinsons?
Stooped, fixed posture Dystonic postures Hypomimia Shuffling Short-stepped gait (+/- festination)
What is lead pipe rigidity?
Constant resistance throughout passive movement
What is cogwheel rigidity?
A superimposed clicking resistance, which is attributed to underlying tremor
How is a parkinsons diagnosis confirmed?
Parkinsonism
No alternative explanation
Dopamine responsivenedd
What should PD patients not present with
Early onset bulbar problems, dementia and hallucinations, preferential involvement of Lower limbs
Prominent eye movement disorder
Intrusive early autonomic problems
What scans can be helpful in parkinsons disease?
Structural brain imaging and SPECT (DaTSCAN) can be helpful
Men are ___ times more likely to develop parkinsons
Men are 1.5 times more likely to develop parkinsons
What are the risk factors for PD?
- Advancing age
- Positive family history- especially if onset <40
- Male gender
- Environmental factors
- Genetics
What decreases the risk of PD?
Tobacco smoking Coffee drinking NSAID use Alcohol consumption CCB use
What increases your risk of PD?
Pesticide exposure Prior head injury Living rurally Beta Blocker use Well water drinking
What is the most clinically relevant pathogenic mutation for PD
Autosomal dominant- LRRK2
Autosomal recessive- PARKIN
How do symptomatic treatments for PD work?
By enhancing intracerebral dopamine concentrations or stimulating dopamine receptors
What are the symptomatic drugs for parkinsons?
Levodopa
Dopamine agonists
Monoamine oxidase type b inhibitors
Amantadine
Bradykinesia and rigidity respond reliably to ________ treatment in early disease
Bradykinesia and rigidity respond reliably to dopaminergic treatment in early disease
MAO B inhibitors are ______ effective, ____ and ______ _____ are needed for more severe treatment
MAO B inhibitors are moderately effective, levodopa and dopamine agonists are needed for more severe treatment
Tremor is inconsistency responsive to treatment with dopamine and so may require
Anticholinergic agents, trihexyphenidyl, clozapine
What are dopamine agonists and levodopa associated with?
Nausea, daytime somnolence and oedema
When do impulse control disorders, including; pathological gambling, hyper sexuality, binge eating, compulsive spending occur?
With dopamine agonists
When should dopamine agonists be avoided?
If there is a history of addiction, OCD or compulsive personality.
Avoided in elderly who have congitive impairment- can cause hallucinations
What is longterm use of levodopa associated with?
motor complications (dyskinesia and motor fluctuations)
What are motor fluctuations?
Alterations between periods of good motor symptom control (on time) and periods of reduced motor symptom control (off time)
What are non-motor fluctuations?
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 occur most frequently?
When levodopa concentrations are at their maximum (peak dose)
What is biphasic dyskinesia?
Involuntary movements that develop at the beginning or the end of a levodopa dose
What is drug induced psychosis?
Hallucinations include minor phenomena, such as the sense of presence or passage hallucinations, but also well-formed visual and less-commonly non-visual (tactile, auditory, olfactory) hallucinations.
Other psychotic features might include illusions and delusions (often with paranoia)
What are some non oral therapies for PD?
Deep brain stimulation, DUODOPA, continuous apomorphine infusion
Define bradykinesia
Slowness of movement with progressive loss of amplitude or speed during attempted rapid alternating movement of body segments
How can bradykinesia be assessed?
Ask the patient to perform some repetitive movements as quickly and widely as possibly (opening and closing the hand, foot tapping)
OR
Global assessment of spontaneous movements of the patient (standing up)
What is micrographia
Progressively smaller handwriting
When does a parkinsonian tremor dissapear?
With active movement
What is the most distinguishing resting tremor in PD?
Poll-rolling type
In clinical practice when is tremor best observed?
When patient is focused on a particular task (counting back from 100)
What is ridity?
Increased muscle tone felt during examination by passive movement
What distinguishes rigidity from spasticity?
It doesn’t increase with higher mobilising speed
Describe parkinsonian gait
- Slow, occurs at narrow base with short, shuffling steps
- Decreased arm swing
- Slow turning with multiple small steps
- Freezing
- Festination
Describe the investigations required for PD diagnosis?
- Rule out treatable conditions of asthenia (hypothyroidism, anaemia)
- structural brain imaging
- possible dopamine functional imaging
- positive levodopa (or s.c. apomorphine) challenge
- genetic testing
What is dopamine functional imaging
PET with fluoro-dopa (limited availability and high cost)
Dopamine transporter imaging with single photon emission CT (DAT- SPECT)
Describe vascular parkinsonism
Affects predominantly lower limbs
Rest tremor is uncommon
Other signs of vascular lesions might be present (spasticity, hemiparesis, pseudo bulbar palsy)
Vascular Parkinsonism will have a poor ______ response
Vascular Parkinsonism will have a poor levodopa response
What will guide the diagnosis of vascular Parkinsonism?
Structural brain imaging
Describe the presentation of of drug induced parkinsonism
Symmetrical parkinsonism
Coarse postural tremor
Presence of other drug induced disorders
- orolingual dyskinesias, tardive dystonia, akathisia
Describe essential tremor
Symmetric, postural or kinetic tremor with higher frequency (up to 12Hz)
Infrequently observed at rest
Often autosomal dominant inheritance with mean onset of 15 years
Alcohol responsiveness
Head tremor- if present- mild
What is the core triad of multi system atrophy?
Dysautonomia, cerebellar features and Parkinsonism
Multi system atrophy is a common cause of degenerative _______, the age of onset is in late __ or __ decade.
Multi system atrophy is a common cause of degenerative Parkinsonism, the age of onset is in late 6th or 7th decade.
What features are suggestive of multi system atrophy?
- severe dysarthria or dysphonia, marked antecollis, inspiratory signing, orofacial dystonia
What may you see on an MRI of multi system atrophy?
Cerebellar and pontine atrophy (hot cross bun sign, or hyper intense rim surrounding the putamen in T2 weighted sequence)
What is progressive supra nuclear palsy?
Symmetric akinetc-rigid syndrome with predominantly axial involvement
Describe the presentation of progressive supra nuclear palsy
- Gait and balance impairment
- vertical gaze supranuclear palsy
- pseudo bulbar symptoms
- retrocollis
- continuous activity of the frontal muscle with eyes wide open (staring)
- frontal-subcortical cognitive deficits
- some patients may present with Parkinsonism
Not usually a tremor
does progressive supranucelar palsy respond to levodopa?
No
What are the core symptoms of fragile X-tremor ataxia syndrome (FXTAS)
Cerebellar gait ataxia, postural/intention tremor, variably Parkinsonism, dysautonomia, cognitive decline of frontal type, and peripheral neuropathy
How does FTAX present on MRI?
MRI with T2 hyperintensities in the middle cerebellar peduncles (MCP sign)
What are motor fluctuations and dyskinesias thought to result from?
Pulsatile stimulation of striatal dopamine receptors in later disease stages
Pharmacological strategies to reduce dopamine fluctuations include the additions of;
A dopamine agonist
Monoamine oxidase type b receptor
Catechol-o-methyltransferase
What might cholinesterase inhibitors such as rivastigmine be used for in PD?
Visual hallucinations and delusions in PD patients with dementia
What does serotonin 5-HT inverse agonists primavanserin do?
Reduces positive psychotic symptoms
Late stage dementia in PD is treated with?
Rivastigmine
What are the surgical treatments for PD?
Deep brain stimulation for treating motor symptoms/complications is well established targeting either the subthalamic nucleus or globes pallidus internus
