Movement disorders Flashcards
Primary output from basal ganglia
Inhibitory projections from GPi/SNr to thalamus
Direct pathway
Caudate/putamen -x GPi/SNr -x Thalamus
(inhibition of inhibition = disinhbition)
Indirect pathway
Caudate/putamen -x GPe -x STN -+ GPi/SNr -x Thalamus
Where are inclusions in PD/DLB?
MSA?
PD/DLB: Neuronal intracytoplasmic inclusions (Lewy bodies)
MSA: Oligodendroglial inclusions
Atypical parkinsonism with retrocollis?
Anterocollis?
Retrocollis: PSP
Anterocollis: MSA
Hot cross bun sign
MSA
What are astereognosis and agraphesthesia?
What are they associated with?
Astereognosis: inability to recognize object in hand
Agraphesthesia: inability to recognize numbers/letters drawn in hand
Both a/w CBS
Secondary parkinsonism associated with “cock walk” (toe walking with elbow flexion)
Manganese toxicity
(Also a/w psych sx - “manganese madness”)
Genetic cause of Wilson’s disease
AR mutation, in copper-transporting P-type ATPase, ATP7B (leads to inability to excrete copper into bile)
“Panda sign” - what is it, what is is seen?
T2 hyperintensity in midbrain but sparing red nucleus (“eyes”) and substantia nigra (“ears”)
Seen in Wilson’s disease
MRI findings in Wilson’s disease
T2 hyperintensity in putamen and also midbrain (sparing red nucleus and SN, leading to “giant panda sign”)
Treatment of Wilson’s disease
- Penicillamine or trientine
- Zn supplementation (impairs copper absorption)
- Low copper diet
Genetic disease associated with orolingual dystonias (e.g. tongue protrusion dystonia)
Chorea-acanthocytosis, a form of neuroacanthocytosis
Genetic cause fo chorea-acanthocytosis
AR, mutation in VPS13A (vacuolar protein sorting-associated protein 13A, aka chorein),
Neurocanthocytosis associated with low cholesterol and vitamin E
Abetalipoproteinemia
Genetic cause of DRPLA
AD, CAG repeat in ATN1 (atrophin 1)
3 forms of neuroacanthocytosis
- Chorea-achanthocytosis
- Abetalioproteinemia
- McLeod disease
Genetic cause of abetalipoproteinemia
AR, mutation in MTTP (microsomal triglyceride transfer protein)
(Involved_in_synthesis_of_some_beta-lipoproteins,_leads_to_inability_to_form_chylomicrons_and_VLDL)
Neurological manifestations of abetalipoproteinemia?
- Ataxia
- Peripheral neuropathy
- Vision loss due to retinosis pigmentosa
Typical initial presentation of abetalipoproteinemia?
FTT w abdominal distension and steatorrhea in early childhood
What 2 related genetic movement disorders commonly have seizures?
Chorea-achanthocytosis and Mcleod syndrome (both neuro-acanthocytosis)
Genetic syndrome with dystonia and myoclonus
DYT1, aka myoclonus-dystonia syndrome
X-linked syndrome with dystonia and parkinsonism
DYT3
Adult-onset craniocervical dystonia with laryngeal involvement
DYT6
Genetic dystonia with diurnal variation, worse in afternoon and evening
Dopa-responsive dystonia
Most common genetic cause of dopa-responsive dystonia
AD mutation in GCH1 (GTP cyclohydrolase I) - involved in dopamine synthesis pathway.
Lesions where can lead to palatal myoclonus?
Guillain-Mollaret Triangle:
1. Dentate nucleus in cerebellum
2. Inferior olive
3. Red nucleus
(Can also be idiopathic)
(Mnemonic:_tooth_eating_olive_with_red_pepper)
Time courses of paroxysmal kinesigenid dyskinias (PKD), paroxysmal nonkinesigenid dyskinesia (PNKD), and paroxysmal exertional dyskinesias (PEDs).
Which responds to ASMs?
WHich may respond t ketogenic diet?
PKD: seconds - 5 minutes. Responds to ASMs.
PNKD: 2 minutes - hours.
PED: 5-30 minutes, rarely 2 hours. May respond to keto diet if due to GLUT1 mutation
One genetic cause linkes to each of paroxysmal kinesigenid dyskinias (PKD), paroxysmal nonkinesigenid dyskinesia (PNKD), and paroxysmal exertional dyskinesias (PEDs).
PKD: PRRT2
PNKD: MR-1
PED: GLUT1
Features of episodic ataxia types I - IV: clinical pattern and duration
EA1: Ataxia + Facial twitching + myokymia or neuromyotonia. Seconds-minutes (can be triggered by startle, movement, or exercise)
EA2: Ataxia + Nystagmus and dysarthria. Minutes to hours (can be triggered by stress or alcohol)
EA3: Ataxia + tinnitus and vertigo (myokymia between attacks)
EA4: Ataxia + eye motion abnormalities
POtential treatments for episodic ataxias 1, 2, 3
EA1: ASMs
EA2: Acetazolamide
EA4: Acetazolamide
Genes associated with EA1 and EA2
EA1: KCNA1
EA2: CACNA1A (also a/w familial hemiplegic migraine, different mutations a/w SCA6)
Genes in which neurotransmitter are associated with hyperkplexia (exaggerated startle that does not habituate)
Glycine (inhibitory transmitter in spinal interneuronas)
Primary output cell of the cerebellar cortex?
Where do they project?
Neurotransmitter?
Purkinje cells
Project to deep cerebellar nuclei (dentate, emboliform, globose - which in turn send excitatory signals to the thalamus)
GABA
Where to fibers from deep cerebellar nuclei travel to as they leave the cerebellum?
Where do they synapse?
Ipsilateral superior cerebellar peduncle -> Contralateral thalamus
Which peduncles do afferent and efferent fibers to the cerebellum pass through?
Efferent: Superior Cerbellar Peduncle only
Afferent: All 3 peduncles (although a minority of fibers in superior cerebellar peduncle)
Which SCA is associated with retinopathy leading to vision loss?
SCA7
Syndrome of ataxia, parkinsonism, and neuropsychiatric symptoms associated with tendon xanthomas?
Diagnostic test?
Treatment
Cerebrotendinous xanthomatosis (AR defect in pathways that metabolize cholesterols to bile acids)
Serum cholestANOL (cholesterol can be normal and is not specific)
Tx: Chenodeoxycholic acid (bile acid, will replace bile acids and lower cholestanol levels)
(Statins may also be used)
What is striopallidodentate calcinosis a.k.a. Fahr’s disease?
What are causes (5)?
Basal ganglia and cerebellar calcium deposition leading to parkinsonism and ataxia
- Idiopathic
- Genetic (multiple forms, can be AD or AR(
- Secondary hypERparathyroidism (e.g. in ESRD)
- Primary hyERparathyroidism
- HypOparathyroidism
What is the ligand used in DAT scan?
Where does it bind?
I123 ioflupane
Binds to presynaptic dopamine transporter (cocaine analog)
(Therefore, reflects projections to putamen rather than putamen itself)
What is the “eye of the tiger” sign?
What disease is it classically associated with (although nonspecific)?
Globus pallidus hypointensity with central hyperintensity
Classically associated with PKAN (most common NBIA)
What are two NBIA disorders most commonly presenting in adulthood?
Neuroferritinopathy and aceruloplasminemia
NBIA associated with prominent cerebellar atrophy
Associated mutation?
PLAN (PLA2G6-associated neurodegeneration)
Phospholipase mutation
(Also seen in FAHN)
NBIA associated with “eye of the tiger” sign on MRI?
Associated mutation?
PKAN (pantothene-kinase associated neurodegeneration)
A/w gene of same name
NBIA associated with iron deposition in substantia nigra as well as GP?
Associated mutation?
MPAN (mitochondrial membrane protein-associated neurodegeneration)
C19orf12 mutation
NBIA associated with T1 halo of hyperintensity surrounding substantia nigra (“halo sign”)
Associated mutation?
BPAN (beta-propellor protein-associated neurodegeneration) - also associated with early psychomotor regression leading to static encephlopathy in childhood
Mutation in WDR45 (WD repeat domain 45)
NBIA associated with prominent white matter changes on MRI
Associated mutation?
FAHN (fattya-acid hydroxylase-associated neurodegeneration) - due to mutation in same gene
NBIA associated with oculogyric dystonic spasms and facial-faucial finger mini-myoclonus?
Associated mutation?
Kufor-Rakeb syndrome (KRS)
ATP13A2 mutation (AR)
NBIA associated with iron deposition in GP but also cortex, caudate, and putamen?
Associated mutation?
Neuroferritinopathy
Ferritin light chain mutations
NBIA associated with iron deposition in caudate, putamen, red nucleus, and thalamus?
Associated mutation?
Aceruloplasminemia
Ceruloplasmin mutations
Antibodies associated with stiff-person syndrome (2?
GAD
Ampiphysin (paraneoplastic
Ataxia associated with high arched feet?
Friedreich’s ataxia
Ataxias with high maternal serum alpha-fetoprotein while affected is in utero?
Ataxia-telangiectasia
Ataxia with oculomotor apraxia (AOM) type 2
Number of repeats for FXTAS?
55-200.
(>200 = fragile X syndrome)
Medication that improves cardiac outcomes in Friedreich’s ataxia?
Idebenone (CoQ10 analogue)
