Movement Disorders Flashcards
Core features of PD?
Core features
- resting tremour
- bradykinesia
- Cogwheeling tremour
Later postural instability often involved but this is later than the other core features
Note pts with PD often present asymnetically, then other side affected when more advanced
Non motor features of PD?
Cognition - PD dementia
Behavioural - hallucination (small people, children, animals)
Sleep - REM sleep disorder
Mood - depression, anxiety
Autonomic (later onset) - Orthostatic hypotension, nocturia and urinary freq, constipation, errectile dys, etc
Additional changes
- hypomimia (mask faces)
- Micrographia (small handwriting)
- hypophonia (soft voice)
- Dysphagia
What are some potential prodromal features of PD?
REM sleep disorder
Mood distirbances (ie depression)
Anosmia (loss of smell)
Pathophys of PD?
Classed as a Alpha synucleinopathy
- Accumulation of intraneuronal protein agregates in the substantia nigra pars compacta
- this affects primerily the dopaminergic neurons in the basal ganglia
Dopamine neurons originating in the substantia nigra pars compact project to the striatum (putamen and caudate).
- There is the indirect (D2) and direct (D1) pathway
- Over-activation of teh Global palidus (internal segment) and the Substantia nigrea pars reticularis causes inhibition of the thalamus
- This leads to inhibition of the cortical pathways causing the impaired movement
PD treatment?
Medications
- Levodopa / aromatic amino acid decarboxylase inhibitor
-> aromatic amino acid decarboxylase inhibitor is included to prevent breakdown of levodopa to dopamine in the peripheries, therefore limiting to brain action
- Levadopa/carbidopa
- Levodopa/benserazide
Dopamine agonists
- Pramipexole - D3 target
- Ritigotine patch - D3 target
- Cabergoline - D1/2 target (not used much anymore due to retroperitoneal fibrosis
Aside from behavioral side effects of cabergoline, what is the main AE?
Retroperitoneal fibrosis
Explain the progressive motor fluctuations and dyskinesias that develop with progressive parkinsons disease?
Effectivly the theraputic window for dopamine gets more narrow as PD progresses
- WIll often need more dose to achieve the effect, but will have more side effects with that dose than before (ie narrow theraputic window)
The progressive dysklinesias are due to increased sens of Dop receptors in brain as disease progresses
How to change dosing regime in pt getting motor fluctuations and dyskinesias due to PD?
Increase freq dosing, decrease each dose (ie aim to sustain more constant controlled level)
2x relevant enzymes involved in dopamine metabolism?
MAO
COMT
Examples of MAOB inhibitors?
- Rasaligine
- Selegiline (Old)
- Safinamide (new MAO B inhibitor that includes a glutamate release inhibitor to increase the ‘on’ time without dyskinesias)
COMT examples?
Entacapone
- Combination with levadopa/carbiudopa is called Stalevo
Opicapone
- same as entacapone but once a day formulations
Other PD treatment specifically for dyskinesias?
Amantadine (initially dev for flu A, but found to have dopaminergic action)
What are the three main advanced treatments for PD (pharm and non pharm)?
Apomorphine injection / infusions pump
- Dopamine agonists
Duodopa (levidopa/carbidopa intestinal gel)
- infusion pump PEJ tubeto avoid stomatch
Deep brain stimulation
- electrode into subthalamic nucleus (STN) or globus palidus internal segment (GPi)
Treatment of PD hallucination (if troubling)? what about when cant decreased levadopa?
Initially reduce dopamine medication
If cant reduce dopamine then clozapine in examinations
- only drug with evidence in this space
- Side effect of neutropenia
Practically used quitiepine but no evidence to support this
Treatment of depression in PD?
TCAs (amytriptaline and nortryptiline) and Pramipexole are only drugs with evidence in trial
Practically just use standard depression drugs
Treatment of PD REM sleep disorder?
Usually clonazapam or TCAs
- nil trials in this space
Features of LBD?
Fluctuating attention and congition
REM sleep disorder
Visual hallucinations + non visual hallucinations
Delusions
Antipsychotic sensitivity
Parkinsonism - usually not all the features of PD
PD dementia vs LBD main difference
PD = motor sx for >12 months prior to dementia
LBD = dementia predominate, with additional motor features
LBD pathyphys?
Like PD it is alpha synuceilopathy with Lewy bodies more in the cortex in addition to substantia nigra par compacta
Treatment of LBD?
Can use levodopa but can sig exacerbate cognitive and behaviours Sx
Beware antipsychotics (1st and second gen) because highly sensative ands will develop neuroleptic SE quickly
Can use acetyl cholinesterase inhibitors for cognitive Sx
Antidepressants
Features of essential tremour? What is ET plus?
Classic action temour - bilateral UL +/- head +/- postural tremour 4-12Hz (ie higher frequ than PD pill rolling which is usually 4Hz)
Can also have voice tremous or LL tremour less commonly
usually early onset, gradual progression
Often improves with etoh
ET plus is ET but with additional features such as dystonic posturing, some cognitive impariment etc
Treatment for ET? medications and more advanced therapoies?
Beta blockers (usually propanolol)
Primidone
Others: topirimate, clonaz
Advanced:
- DBS and focused ultrasound thalamotomy
Subtypes of Multiple system Atrophy?
Parkinsonian subtype
- Parkinsonism features
Cerebellar subtype
- ataxia / apendicular ataxia
How to differentiate parkinsonian subtype MSA from PD?
early autonomic dysfunciton in MSA (wont have this until late PD)
Features of MSA?
Prominent autonomic dysfunction
- erectile dysfunction, urinary incontiunence, postrural instability hypotension
- Features of parkinsonism (if PD subtype) OR features of ataxia (if cerebellar subtypes)
Other features:
- Stridor and OSA
- Dysphonia, dysarthria, dysphagia
- Tremour (much more jerky than PD, not typical looking)
- Postural instability (antecollis, pisa syndrome)
- Emotional instability and REM sleep disorder
Pathophy of MSA?
alpha synucleinopathy (inclusions in glial cells)
- If affects the nigrostriatal structure = PD subtype
- If affects other structures = cerebellar subtype
Treatment of MSA?
Levodopa for MSA-P (often exacerbates teh orthostatic hypotension so difficult balance)
FLudrocortisone, midodrine for management of orthostatic Hypotension
Mirabegron, oxybutanynin for urinary dysfunction
What are the features of Progressive supranuclear palsy?
- Falls, often backwards
- Slowed down saccades, OR (when more advanced) Inability to look up, but dolls head positive
- Impaired postural reflexes (more than 3 steps backwards to get balance back)
- Axial rigidity and retrocollis
Other features:
reduced facial expression
reduced arm swing
Difficulty doing up buttons
Pathyphys of PSP?
Tau protein deposition around perinuclear glial inclusions
- Atrophy of midbrain causes humming bird sign on sagital imaging
Treatment of PSP?
Levodopea (usually doesnt work)
Amantadine
Features of corticobasal degeneration?
- Difficulty brushing teeth, using cutlery on one side
- Sensory inatention and dysgraphesthesia
- Ideomotor dyspraxia
- Limb apraxia (alien limb)
- Slowed speech with long pauses between words, speech apraxia (expressive aphasia)
- Parkinsonism
Features of huntingtons disease?
Chreiform movements of trunk and upper and lower limbs
Imperistance of tongue protrusions
saccadic intrusion of smooth pursuit and slow initiation of saccades
Cognitive impariment
Often unaware that there is an issue, may have personality changes
What neurons does huntingtons disease effect?
GABAergic neurons in basal ganglion (ie caudate and putamen)
Treatment of huntingtons disease
antipsychotics
How does a triplet repeat lead to huntingtons disease?
Translates to a long protein
Tardive dyskinesia. what is it?
How is it different from drug induced parkinsonism?
Delayed onset of orofacial dyskinesias in the context of antipsychotic use
- Treatment: reduce dose, change to newer antipsychotic, tetreabenezine, benztropine
Drug induced parkinsonism can also be uinduced by antipsychotic use. Presentation is symmetrical extrapyradidal signs
Hemibalismus. Where is the leision?
contralateral subthal nucleus
Liver affected + neurological signs and sympotms. what is the disease?
Wilsons
Ix in WIlsons disease?
Treatment?
Low serum cearuloplasmin, high urinary copper
High copper on liver Bx
Chelating agents such as penicillamine, zinc
Restless legs can be primary or secondary. what are some causes of secondary?
Peripheral neuropathy, Iron deficiency, end stage renal disease, preg, drugs
What is one difficulty about treating restless legs?
Augentation
- more drug is often required to manage condition
Gait disturbance + urinary incontinence+ cognitive impariment. what is the condition?
NPH
