Movement disorders + laughing Flashcards
What is the major neurotransmitter within the striatum and pallidum
GABA / inhibitory
What is the main output structure of the basal ganglia projecting to the thalamus?
GPi
What is GPi main role
It receives info from striatum via direct/indirect pathway AND its job is to INHIBIT the THALMAUS
What is dopamine effect on movement?
Dopamine facilitates movement
possible enzyme deficits in dopa-responsive dystonia
- tyrosine hydroxylase
2. GTP cyclohydrolase 1
What are the ways the striatum influences the Globus pallidus (2 paths)
- Directly to the GPi (excitatory D1) which inhibits thalamus
- via GPe (inhibitory D2) then STN then GPi
Diagnostic screening tests in Wilson’s dz?
screening: high 24 hr urine copper and low serum ceruloplasmin
child or young adult with twisted foot, gait abnormality, juvenile parkinsonism
may be dopa-responsive dystonia which is treatable with low dose l-dopa!
Red flags (3) you aren’t dealing with pure parkinsonism
- ataxia
- weakness
- spasticity
toxicity in Welders that may lead to parkinsonism
manganese
Top 3 dx to consider instead of Parkinson disease in the young
- Wilson’s
- Dopa responsive dystonia
- huntington’s can have no chorea and more PD sx in young
Autosomal dominant mutation w/ successive generations of PD with normal onset age 50-70
LRRK2 mutation
more rare cause of dominant inheritance of PD with younger onset?
SNCA alpha synuclein (PARK-1)
most common cause of young onset PD that is not present in successive families’
- tends to have dystonia, and diurnal variations with improvement with sleep
- response to tx?
Parkin gene, good l-dopa response, absence of Lewy bodies
(Autosomal recessive)
(PARK 2: wen teen goes Parkin looking for sex: Chr 6)
what are Lewy bodies made up of?
alpha synuclein
ubiquitin
neurofilament protein
dose of levodopa considered a fair trial?
at least 900-1000mg/day (300 TID)
3 nonmotor sx in PD that may precede motor sx
- REM behavior disorder
- anosmia
- autonomic dysfunction
early severe presentation of autonomic dysfunction suggests what?
MSA: Multiple system atrophy
REM behavior disorder in isolation is highly predictive of what?
an alpha synucleinopathy
Deep brain stimulation improves what (4) and has no effect on what (1)
DBS good for:
- improving dyskinesias to best dyskinesia-free ON state on meds alone
- reduced med requirements
- improved ON time
- reduced OFF time
Does not effect postural reflexes
Contraindications for Deep brain stim for PD?
severe psych disease, cognitive impairment, postural instability (may worsen it)
Most effective and best tolerated med for PD and how does it work
levodopa with carbidopa which prevents it from getting broken down before it gets to the brain
What are ropinirole, pramipexole, and apomorphine?
What is the role? Benefits / disadvantages
dopamine agonists
they are less effective and have more s/e than ldopa for pd BUT they have less dyskinesias particularly in young patients who are at more risk for dyskinesias with levodopa
5 main med categories for PD
- Levodopa
- DA agonist
- Anticholinergics
- MAO-B inhibitors
- Amantadine
med that is rarely used but can prolong duration of effect of levodopa
entacapone (COMT inhibitor)
major side effects of levodopa
dyskinesias, vivid dreams/illusions/hallucinations (esp in older cognitively impaired pts), dizziness, hypotension, somnolence
major s/e of Dopamine agonists
worse hallucinations/nausea
sleep attacks
compulsive behaviors
when do dyskinesias usually occur with PD med treatment / levodopa
at peak of ON
order of options in patient on multimedications for PD and who are having cognitive / psych side effects (3)
- get off anticholinergics –> amantadine –> MAOB–>DA agonist –> levodopa (keep the ones with best efficacy and least s/e)
- add Rivastigmine which is a cholinesterase inhibitor approved for PD dementia
- lastly add antipsychotic but be very careful (black box warning)
Best two antipsychotics in PD least likely to worsen PD
Quetiapine and clozapine
Tao or alpha synuclein?
Multiple system atrophy
alpha synuclein
Tao or alpha synuclein?
Progressive Supranuclear Palsy
Tao
Corticobasal degeneration
Tao or alpha synuclein?
Tao
Tau or alpha synuclein?
PD
Parkinson disease - alpha synuclein
Tau or alpha synuclein?
Lewy Body dementia?
Alpha synuclein
Parkinsonism with very early falls?
supranuclear vertical palsy
diseases that are less likely to respond to ldopa
PSP and CBD
PD + disease with alien hand or unilateral limb dystonia or apraxia
corticobasal degeneration
Number of repeats with Huntingtons premutation that can pass down for anticipation/expansion (unstable)
Normal level
Level needed for disease
normal 40 with full prenetrance
impaired saccade initiation and speed with need for head movements
huntington disease
Possible treatment of huntingtons disease chorea
tetrabenazine dopamine receptor blocker but depletes all monoamines so can deplete 5HT and worsen depression
Meds that can cause myoclonus (5)
- SSRI
- TCA
- lithium
- opioids
- stimulants
palatal myoclonus suggestive of what?
brainstem lesion
meds that may be helpful for myoclonus? (3)
VPA, keppra, clonazepam
meds (4) that are known for causing action tremor
- amiodarone
- amitriptyline
- cyclosporine
- VPA
MEds that may be helpful for action tremor (2)
nonselective BB like propanolol
primidone
best treatment for focal / segmental dystonia like cervical dystonia?
botox
best way to manage drug-induced parkinsonism
d/c offending agent or reduce it (may take 3 mos)
may consider adding anticholinergic or amantadine
ldopa, receptor blockers are not usually helpful
major risk factor for Neuroleptic malignant syndrome
dementia with Lewy bodies (dont tolerate antipsych meds)
3 basal ganglia toxins and their specific spot of damage
- carbon monoxide: GP
- methanol: putamen
- MPTP: parkinsonism
Ddx abetalipoproteinemia from Freidreich’s ataxia
both can cause progressive ataxia BUT Friedreichs has cardiomyopathy and abetalipoproteinemia has lots of other stuff like cholesterol/TG issues, acanthocytosis, diarrhea, AND finally, retinitis pigmentosa
Gene causing alternating hemiplegia of infants/toddlers and what is treatment
Bonus: same gene causes something else too
ATP1A2 chr 1q23
Tx w/ flunarizine
also causes familial hemiplegic migraine 2
loss of reflexes and joint position sense in feet but upgoing toes, thing of what?
Friedreich ataxia
Disease that looks like huntington’s disease and is also due to a CAG expansion, that causes chorea dementia, and ataxia, and in younger kids really has mostly progressive myoclonic epilepsy. What chromosome?
Dentatorubral-Pallidoluysian Atrophy (DRPLA) on chr 12 (not 4 like Huntingtons)
how to diagnose dopa responsive dystonia?
CSF for neurotransmitters
-disease is due to BH4 synthesis problem (GTP cyclohydrolase 1 def) or Tyrosine hydroxylase deficiency that prevents tyrosine from being converted to levodopa
episodic ataxia 1 is associated with what channel defect / gene, what clinical findings, and what duration of attack
K channel on chrom 12
MyoKymia
lasts Minutes
episodic ataxia 2 is associated with what channel defect / gene, what clinical findings, and what duration of attack
Calcium gene chrom 19, Nystagmus, responds to Acetazolamide Attacks last Hours (19 instead of a short 12 where EA-1 is) AND: Ca (2+: EA-2 vs K (1+: EA-1) AND EA-2: two eyes for nystagmus
disease with bilateral calcifications of basal ganglia and subcortical dementia, psychiatric sx, and parkinsonism
Fahrs disease
who gets fragile X associated tremor/ataxia syndrome?
Affects what brain areas
men who have premutations and may have grandsons w/ dz
Affects middle cerebellar peduncles
mutation in Friedreich’s ataxia
GAA expansion on chr 9 (FRDA gene)
When does Friedreich ataxia present compared to ataxia-telangiectasia?
older in FReidreichs: 13
early childhood: ataxia-telangiectasia
what chromosome and gene in ataxia telangiectasia
ATM chr 11
Disorder with extrapyramidal sx in infancy, hypotonia, and MRI w frontotemporal atrophy with bat-wing appearance
Glutaric acidemia type 1
where is the lesion in hemiballismus?
contralat subthalamic nucleus
Huntington Disease gene mutation chromosome
CAG repeat Chr 4
Catch Animal Game, Hunt FOUR Animals
akinetic, dystonic form of huntingtons?
westphal variant
how does juvenile huntington present
more like parkinson and dystonia and myoclonus/sz
path finding in huntingtons
loss of Gaba neurons in striatum
presentation and cause of hyperekplexia?
exaggerated startle in infancy / apnea
caused by glycine receptor mutation chr 5
cerebellar ataxia, cerebellar atrophy, cataracts, ID, hypotonia, weakness, primary gonadal failure, scoliosis
Marinesco-Sjogren syndrome
(Maraschino cherries ridiculous mnemonic)??
neuroacanthocytosis (RBC spiky) that is x-linked and is associated with facial tics and axonal peripheral neuropathy
McLeod syndrome
Oromandibular dystonia with blepharospasm
Meige syndrome
hot cross bun sign is what and seen in what
seen in MSA multiple system atrophy from degeneration of pontocerebellar fibers causes brainstem above 4th vent to look like it has cross septations
antibody seen in adults with opsoclonus-myoclonus syndrome
Ab to Ri (ANNA-2)
essential vs symptomatic palatal tremor
essential: tensor veli palatini: eases in sleep
Symptomatic: from levator veli palatini and is moved by soft palate and continues in sleep
lesion of triangle of Guillain-Mollaret may cause what
palatal tremor
eye of the tiger MRI sign
PKAN / iron accum in brain
what correlates witih gait abnormalities in Parkinsons
loss of neurons in pedunculopontine nucleus (PPN)
possible treatment for paroxysmal dyskinesias
carbamazepine or phenytoin
PD like illness with jerky eyes and backwards falling
PSP
postural stability is poor
What is the ramsay hunt syndrome thats a movement disorder
progressive myoclonic ataxia…
accumulation of phytanic acid occurs in what disorder and what are the sx?
cerebellar ataxia, retinitis pigmentosa, polyneuropathy
antibodies in stiff person syndrome
what pts are at risk
anti-GAD Abs
may be paraneoplastic SCLC or breast
wing beating tremor, sunflower cataracts, bulbar dystonia, dysarthria, drooling
Wilsons
giant panda face on MRI
Wilsons (midbrain)
Wilson’s gene?
ATP7B on chr 13q
serotonin syndrome vs NMS?
myoclonus in serotonin syndrome
rigidity in NMS
Most common autosomal dominant inherited ataxia in US?
Machado-Joseph disease SCA-3 (spinocerebellar atrophy 3)
type of ataxia: slow clumsy, wide based, constant shifting of position to maintain balance. Titubation
cerebellar ataxia
type of ataxia: steppage gait, irregular striking of floor, wide based
sensory ataxia (loss of jp sense)
sewaga variant dystonia?
dopa responsive
