Neurology 1(B) - Movement Disorders Flashcards
(39 cards)
What are the Dx criteria for Restless leg syndrome?
Urge to move legs accompanied by unpleasant sensations
Worse when inactive
Partially or totally relieved by movement
Circadian rhythm - worse in evening or night than day
Associated and supporting features: FHx, dopa response, PLMS
What is the classification of restless leg syndrome?
Primary Secondary - Fe deficiency - ESRD - Pregnancy - DM - RA - PD
What are treatment options in RLS?
Improve sleep hygiene Avoid exacerbating factors - caff, EtOH, SSRIs, dopamine blockers, TCAs Levodopa Dopamine agonists (Pramipexole) Gabapentin (CBZ, valproate) Opiods Tramadol BDZ Irone, Mg, clonidine
What are dopamine related Sx in PD?
Fluctuations, involuntary movements, neuropsychiatric
Motor disability
Reduced on and off
What are non-dopamine related Sx in PD?
anosmia Depression personality change Lethargy, pain REM SBD Balance, gait, swallowing, speech Mood Sleep, pain Cognition Autonomic
What are exogenous risk factors for PD?
Well water rural environment non-smoking pesticide/herbicide exposure minor head trauma Positive FHX - greatest RF
What is the mechanism of nigral cell death in PD?
induced mitochondrial respiratory failure and oxidative stress in nigral neurons
- ox stress, free rad formation
- mito dysfunction
- excitotoxic damage
- protein mishandling
- inflammation
- cell death, apoptosis
4-12% loss/year, 10x normal
4-6y presymptomatic period
What are levodopa associated disabilities in PD?
Motor fluctuations - 10%pa (80% by 10y)
- wearing off, end of dose, subtle psychomotor
- on-off, random, brittle, sudden increased magnitude
- assoc involutnary movements, pain, akathesia, mood, autonomic
Dyskinesias
- variable disability
- peak dose, off phase, dystonia, diphasic
- vary between pts but remain consistent for all patients
Neuropsychiatric toxicity - 60%
- major dose limiting effect
- common in later disease, elderly, cognitive impairment
- correlates with LB density in amygdola, parahippocampus, inferior temporal cortex
Reduced response
What features of parkinsons are not responsive to levodopa?
falls, instability, gait disturbance
Swallowing, speech disturbance
cognition - concentration, attention, memory
Depression, anxiety
sleep disturbance
incontinence, hypersalivation, constipation
fatigue, pain
What are predictors for cognitive impairment in AD?
Attention, working memory, reduced processing speed are features, similar to AD
Predictive factors:
- age
- age at disease onset
- duration of disease
- akinetic-rigid disease pattern
What is the congnitive profile in PD?
dysexecutive syndrome impaired attention memory -free recall difficulties visuospatial dysfunction behavioural and personality changes language and praxis generally preserved less often - amnestic syndrome with early language involvement
What are core Dx features of Dementia with lewy bodies?
Cognitive decline (70%)
fluctuation in cognition/attention
visual hallucinations
motor parkinsonism (95% eventually)
What are other clinical features of DwLB?
age of onset 75y
duration 7 years
rate of decline 4 MMSE/year
What are features of levodopa?
gold standard treatment of PD 95% response rate honeymoon period increased survival - 9 to 14y no clinical evidence of neurotoxicity low acute SE profile
What are examples of dopamine agonists?
Ergoline agonists - bromocriptine, pergolide, cabergoline
Pramipexole
What are features of dopamine agonist monotherapy?
less powerful control of motor symptoms
lower risk for developing dyskinesias or motor fluctiations
pramipexole has antidepressant action
as adjunct to levodopa - improves motor control, reduces off time, and limits need for levodopa
What are risks of ergot derived dopamine agonists?
Fibrosis!
thickening retraction and stiffening of heart falves, due to high affinity to 5-HT(2B) - expressed in heart valves, mediate mitogenesis and proliferation of fibroblasts
mod severe valvular regurgitation in 23% pergolide, 28% cabergoline
cumulative dose effect
What are features of non-ergot derived agonists of dopamine?
Pramipexole - significant reduction in off hours on levodopa, lower fluctuations in dyskinesias vs levodopa
effective, delayed motor complications c.f. levodopa
What are significant AEs associated with pramipexole?
somnolescence nausea or vomiting dizziness hypotension involuntary movements hallucinations fatigue confusion rash Impulse control disorders!
What are features of rotigoline?
Transdermal dopamine agonist patch
effective in early and late disease
not affected by food or gastric emptying
What are features of impulse control disorders?
complex behaviours related to aberrent or excessive dopamine receptor stimulation - pathological gambling, hypersexuality, compulsive shopping or eating
Caused by dopamine agonists, not by entacapone.
Levodopa does cause punding at high doses
What are RFs for Impulse control disorders?
Younger age, males
Dopamine agonists - dose related pramipexole > ropinirole > pergolide
Premorbid novelty seekins, risk taking, alcohol abuse, pathological gambling
FHx
What are features of entacapone?
COMT inhibitor - prevents extracerebral metabolism of levodopa
doubles the t1/2 of levodopa
increases bioavailability by 35%
useful in moderate flucuations
SEs: discolouration, diarrhoea, increased levodopa SE, postural hypotension, neuropsychiatric, dyskinesia, nausea
What is selegiline?
MAOB inhibitor
- effective as symptomatic monotherapy
- efficacious as adjunct to levodopa, mild effect
