Movement Flashcards
Direct pathway
Substantia nigra pars compacta D1 neurons activate striatum (caudate/putamen)
Cinnamon Candy Great in Taste: cortex ->caudate/putamin->globus pallidus internus ->thalamus
Only SNc, cortex, thalamus positive outputs
Indirect pathway
Substantia nigra pars compacta D2 projections inhibit striatum (caudate/putamen)
CCGeSGiT
Cinnamon Candy Great Excitement and Supergreat in Taste: cortex ->caudate/putamin->globus pallidus externa -> STN -> GPi/substantia nigra pars reticulata ->thalamus
Only STN, thalamus, cortex positive outputs
Basal ganglia neurotransmitter
Glutamate
Vascular Parkinson’s
Upper extremities usually spared
Non motor PD Sx
Shoulder pain bc less movement of joint
Constipation
REM sleep behavior not just in DLB
Alpha synucleinopthy vs tauopathy vs beta amyloid
Alpha syn - PD, LBD, MSA, AD
Tau - CBD, PSP, Pick’s
Beta amyloid - AD, CAA, vascular dementia
Pd + dementia criteria
PD present for 1+ yr before dementia
PD path
MSA path
Alpha synuclein deposition
Loss of DA in SNpc
Lewy bodies - neuronal intrachtoplastic inclusions
MSA - oligodendroglial inclusions
PD genes
- LRRK2 mutation - AD, common cause familial PD
- Parkin (PARK2 gene) - AR, juvenile onset
- alpha-synuclein (PARK1 gene) - AD- young onset - synaptic vesicle trafficking problem
tolcapone
-Tall Al Capone gangster: tolcapone (a peripheral and central COMT inhibitor) increases the bioavailability of L-Dopa in periphery + CNS
-Hepatic gun: tolcapone can cause hepatic failure
entacapone
Al Capone gangster at entrance:
-a peripheral COMT inhibitor-increases the bioavailability of
levodopa
carbidopa
peripheral dopa-decarboxylase inhibitor;
it reduces conversion of levodopa into dopamine in the periphery while not inhibiting central conversion
-decreases nausea
trihexyphenidyl and benztropine
Tri-hex Benz car: (antimuscarinic agents used to treat parkinsonism)
-antimuscarinic agents
-Trembling getaway car- improve tremor and rigidity of
PD with no effect on bradykinesia
DBS
-reducing tremor + bradykinesia
- not levodopa-unresponsive gait freezing, falls, or other axial symptoms
STN, GPi
-Ventral intermediate (VIM) nucleus -tremor (PD or ET)
PSP
no ataxia, autonomic Sx vs MSA
-onset 70s, later vs PD, MSA
-symmetric parkinsonism
-downgaze palsy, square wave jerks
-midbrain atrophy-hummingbird
-retrocollis (vs MSA-antecollis)
MSA
alpha synucleinopathy
-glial cytoplasmic inclusions in oligodendrocytes
-antecollis neck
-bilateral rest tremor, ataxic-jerky myoclonic tremor
-mottled cold hands
-inspiratory sigh/gasp, stridor (laryngeal spasm weakness)
-not L dopa responsive (or minimal)
-start in 60s
MSA-A-/Shy-Drager - autonomic dysfxn; syncope
-urinary incontinence - Onuf’s nucleus, impotence, larygneal dystonia (fatal)
MSA-P - parkinsonism- rapidly progressive
*MSA-C-cerebellar ataxia *
-hyperintense putamen rim
-cross buns sign - loss pontocerebellar tract
DLB
cognitive impairment within 1 yr PD Sx
Core clinical features: fluctuating cognition
formed visual hallucinations,
REM sleep behavior disorder
1 cardinal feature of PD
-L Dopa not tolerated; very sensitive to neuroleptics
-can have autonomic dysfxn ~Msa
Washout MIBG scan, no cardiac uptake of isotope , horseshoe shaped gap - in PD and DLB, bc pre and post ganglionic autonomic failure
(normal in MSA bc preganglionic autonomic failure)
CBD
tauopathy
-myoclonus, higher cortical sensory loss, and dystonic posture with absence of prominent falls
Apraxia, can’t follow command
Posturing= dystonia
waving arm around (alien limb) waving fingers around
Myoclonic jerks that looks tremulous
prominently asymmetric
-focal limb rigidity/dystonia,
-alien limb
agraphesthesia
astereognosis
-parkinsonian
drug induced parkinsonism
manganese toxicity (not Mg toxicity)
-welders, miners, chronic liver disease
-parkinsonism without tremor
-psych Sx
-cock walk: toe walking+elbow flexion
-hyperintensity in BG
-carbon monoxide
essential tremor
Tx: propranolol; primidone; topiramate; clonazepam
-4-8 Hz
Tourette’s syndrome
motor+ photic tic (throat clearing)
DA hyper-stimulation ventral striatum + limbic system
Tx: Anti-DA agents such as haloperidol, pimozide, and the atypical antipsychotics.
Clonidine, an α-2-adrenergic agonist, ADHD and other behavioral aspects of Tourette’s syndrome, and improves tics
secondary tourettism -ASD, static encephalopathy, neuroacanthocytosis, HD, medications, infection
complex vs simple tic
complex motor tic: coordinated sequenced movements that resemble normal movements such as truncal flexion or head shaking.
Simple phonic tics include sniffing, throat clearing, grunting, or coughing.
Complex phonic tics include verbalizations such as shouting obscenities (coprolalia), or repeating others (echolalia) or oneself (palilalia)
Amantadine
Tx Peak dose dyskinesia
Wilson’s disease
AR mutation copper transporter -ATP7B.
Tremor: wing beating arms
Grin with drooling
MRI - giant panda - T2 signal in caudate, putamen, midbrain with red nucleus spared
Dx: urinary excretion of copper high, ceruloplasm low in serum
Tx: zinc supplement (binds copper), low copper diet, d penicillamine/trientine dihydrochloride
Huntington’s
Motor impersistence + chorea (vs Wilson’s)
AD, CAG repeat
-can’t test ASx minors until they can consent
Sydenham’s disease
Autoimmune, 1-8 months after infection group A strep or only Sx
-BL chorea , emotional lability
Tx: DA antagonist - antipsychotic
Neuro acanthocytosis
Chorea-acanthocytosis- **SEIZURE + areflexia* Dystonia, chorea in 30s, 40s , self mutilating, tongue protrusion dystonia - VPS13A disease
-elevated CK and liver enzymes
-acanthocytes on smear with little protrusions from cells, does not rule out if negative
Mcleod’s syndrome - XK disease (kell protein blood group); X linked chorea-acanthocytosis - XK disease-middle aged men
-liver problems, decreased reflexes
Abetalipoproteinemia - low serum cholesterol , low Vitamin E
Dentatorubral-pallidoluysian atrophy
AD neurodegenerative, Asian pts
Trinucleotide repeat CAG - atrophin-1 gene chr 12p - choreoathetosis, dementia, ataxia like Huntington
Start in 40s
Hemiballismus
Tx anti DA therapy
Tardive dyskinesia
Tx: clonazepam, tetrabenazine
Primary generalized dystonia
Generalized: At least two body parts involved
AD inherited dystonia - torsin A gene mutation
Sx in childhood, then progress
Not DA responsive
Meige’s syndrome
Blepharospasm
Oromandibular dystonia
Segawa Dopa-responsive dystonia
More in females
AD inheritance, GCH1 mutation (growth hormone and fat ppl on segways, dominant)
Mild Parkinsonism
Diurnal variation - worse in afternoon/
PM
-responds to low dose L Dopa without dyskinesias
Lance Adams syndrome
Months or years after hypoxia
Palatal tremor/myoclonus
Clicks in ear
If from lesion in brainstem - persist during sleep -> Guillian Mollaret triangle dentate cerebellum, inferior olive, red nuc
-can see hypertrophy inferior olive if symptomatic lesion
Paroxysmal kinesigenic dyskinesia
Familial or sporadic
Trigger: startle, sudden movement
Lasts Sec to 5 min
(vs paroxysmal nonkinesigenic dyskinesia - min to hrs; fewer episodes)
Tx: ASMs, carbamazepine
Episodic Ataxia type I
Episodic ataxia type II
Type iii
Type Iv
Type I: KCNA1 potassium channel gene mutation
-facial twitching sec-min
Tx: ASM, carbamazepine
Type II: Brainstem Sx - nystagmus, dysarthria (no facial twitching), HA
min-hrs
-CACNA1A4 Ca channel mutation - also familial hemiplegic migraine
Tx: acetazolamide
Type III: AD, tinnitus, vertigo; myokymia btw attacks
Type IV: ocular motion problem
Stiff person
Tx: benzos, baclofen
Lumbar lordosis, increased tone paraspinal muscles
-if surprise ->get spasm, exaggerated startle response
Age 40s-50s onset
Autoimmune or paraneoplastic
If anti-GAD Ab - can see endocrine problems, insulin dependent DM
Hyperrekplexia
Familial - glycine R, transporter mutations
Glycine: inhibitory neurotransmitter at spinal interneurons
Abnormal spinal la inhibitory interneuron reciprocal inhibition
Sx: exaggerated startle reaction
Dx: rule out startle evoked seizures -
Tx: benzos, valproate
Cerebellum anatomy
Purkinje cells - GABA - inhibitory
Cerebellar efferents - superior cerebellar peduncle
Afferents - inferior CP, middle CP, superior CP, inferior olivary nucleus
Spinocerebellar - afferents = mossy fibers
Acquired cerebellar ataxia
- Celiac disease - ataxia only can have no GI Sx - check celiac AB-anti-gliadin Ab
- Hypothyroidism
- Toxins: mercury, bismuth salicylate, toluene
Friedreich’s ataxia
AR trinucleotide repeat expansion - GAA in frataxin gene
High arched feet, scoliosis
Presents ~young adult
Cardiac conduction abnormalities
Cardiomyopathy tx - idebenone - Coenzyme Q10 analog
Ataxia telangiectasia
AR mutation ATM gene - DNA repair problem
Can’t move eyes without head thrust
Cancer, immunocomp (hypogammaglobulinemia)
-high AFP
Spinocerebellar ataxias
Autosomal dominant starts age 30s-50s
Mostly trinucleotide repeat expansions
Sca1- ATXN1 CAG repeat - presents 30s-40s
Sca2- ATXN2 CAG repeat
Most common: SCA3 - ATXN3 gene-CAG repeat expansion
-facial, tongue atrophy , fasiculations, L dopa responsive parkinsonism
Sca7 - retinopathy, vision loss
Fragile X syndrome
Trinucleotide repeat expansion CGG on FMR1 gene
X linked, affects males more
Dysautonomia, ataxia, parkinsonism
Hyper intensities cerebellum
FHx intellectual disability (vs MSA)
Cerebrotendinous xanthomatosis
AR
Ataxia, Psych Sx, Parkinsonism, tendon deposition fat
Dx: cholestanol not cholesterol bc normal
Fahr disease / striopallidodentate calcinosis
BL calcification BG and cerebellum
Idiopathic or genetic
Any parathyroidism hyper or hypo
Nonketotic hyperglycemia
T1 hyper intensity unilateral striatum
Tx: DA R antagonist if persistent Sx
DAT scan
pre-synaptic DA (does not measure putamen b/c post-synaptic)
-loss of density and intensity in striatum, asymmetrical corresponding with contralateral Sx
PET
fluorodopa - reduced uptake in putamen
neurodegerneration with brain iron accumulation
-parkinsonism, dystonia, choreoathestosis, ataxia - PKAN - eye of tiger
PLAN - PLA2G6
MPAN -
BPAN - beta propeller protein associated neurodegeneration - WD repeat domain 45 gene X linked most female-WDR45
-hyperintense lesion on T1 in cerebral peduncles/substantia nigra midbrain = Halo sign
-psychomotor regression then stable static encephalopathy as kid; then dystonia later
-seizures
Chorea- neuroferritinopathy , aceruloplasminemia
FAHN
Kufor-Rakub
CoPAN
Kernicterus
BL BG / globus pallidus hyperintensity on T2
no loss of olfaction early
MSA, PSP
C9orf72 disease
AD, hexanucleotide repeat expansion - GGGGCC
-most common cause familial and sporadic ALS and FTD
-early behavioral problems, upper motor neuron signs, chorea, dystopia, myoclonus, tremor, PD (phenotype not related to size of expansion)
