Dr. Cheng's board review Flashcards
Which neurodegenerative diseases are synucleinopathies?
Parkinson’s disease MSA dementia with Lewy bodies
Which neurodegenerative diseases are tauopathies?
Progressive supranuclear palsy Frontotemporal dementia corticobasal ganglionic degeneration
How does a DaTscan work?
Ioflupane is the ligand used (cocaine analogue) that binds to presynaptic dopamine transporters. In the setting of SN degeneration, there are reduced projections to the striatum –> thus less binding of dopamine transporter ligand. Crescent-shaped symmetric radiotracer distribution with intensity distinct from background brain is normal
What are the group of disorders called neurodegeneration with brain iron accumulation (NBIA)?
a group of several disorders that are associated with lipid or iron metabolism. It can manifest with movement disorders (ie Parkinsonism, dystonia, choreoathetosis), developmental delay, spasticity, ataxia, or seizures. Usually presents in infancy or childhood. -iron deposition seen in the globus pallidus or other regions (seen on GRE) lots of genetic and phenotypic heterogeneity
What is pantothenate-kinase associated neurodegeneration?
PKAN; most common type of NBIA -due to mutations in patothenate kinase 2 gene -MRI with “eye of the tiger” is suggestive of dx
Cerebrotendinous Xanthomatosis: (1) pathophysiology (2) presentation (3) MRI/lab findings (4) treatment
1) pathophysiology: defect in the enzyme 27-sterol hydroxylase on chromosome 2 –> deposition of cholesterol and cholestanol in brain, lungs, eyes, tendons (2) presents with: neuropsych sx, ataxia, parkinsonism, neuropathy, Achilles tendon xanthomas (3) MRI findings: cortical and cerebellar atrophy and white matter changes elevated serum cholestanol levels; (cholesterol levels can be normal and non-diagnostic) (4) treatment: chenodeoxycholic acid –> decreases serum cholestanol
Describe the frequency seen in orthostatic tremor?
High frequency 14-16 Hz affecting the trunk and thighs
Striopallidodentate calcinosis: (1) pathophysiology (2) etiologies (2) presentation
(1) pathophys: abnormal deposition of calcium in the brain, most commonly in the caudate, but also putamen, thalamus, cerebellum and other places (2) etiologies: can be idiopathic vs familial/genetic vs primary or secondary hyperparathyroidism vs hypoparathyroidism
draw out the metabolism of L-DOPA
Ataxia Telangiectasia
1) presents with:
2) pathophysiology
3) labs
1) presents in childhood with neuropathy, ataxia, EOM abnormalities, and telangiectasia
2) mutation in ATM gene, chromosome 11 resulting in impaired DNA repair
3) increased alpha fetoprotein
The Spinocerebellar Ataxia
1) pathophysiology
2) p/w
3) MRI
1) CAG repeat is most common (genetically heterogenous) –> aggregation of misfolded proteins
2) presents at any age with progressive truncal and limb ataxia with spasticity and UMN signs +/- CN abnormalities, impaired saccades, neuropathy
3) cerebellar atrophy (+/- brainstem and cervical cord atrophy
Fragile X tremor-ataxia synrome
1) pathophysiology:
2) p/w:
3) MRI:
1) expansion of CGG repeat in FMR1 gene on chromosome X > 200 repeats
2) ataxia, tremor, parkinsonism, wide base gait, family hx of metal retardiation
3) T2 hyperintensities in cerebellum and inferior cerebellar peduncle
Workup for acquired ataxia?
check TSH (hypothyroidism); Miller-Fisher variant; post-infectious (varicella zoster)
medication exposures: chemo, salicylates, toluene, bismuth, phenytoin
infections: HIV, CJD, Whipple’s disease
Freidreich’s ataxia
1) genetic defect:
2) p/w:
1) expansion of trinucleotide repeat GAA in frataxin gene chromosome 9
2) p/w: cerebellar dysfunction neuropathy, UMN signs, high arch feet, spinal deformities, cardiomyopathy, and conduction abnormalities
Describe episodic ataxia type 1:
1) presentation?
2) triggers
3) pathogenesis
4) txt
1) p/w facial myokymia or neuromyotonia, lasting seconds to mins occurring several times per day
2) triggers: movement, startle, exercise
3) mutation in KCNA1 on chromosome 12
4) txt: carbamazepine
Describe episodic ataxia II?
1) presentation
2) triggers
3) pathogenesis:
4) txt:
1) p/w brainstem symptoms such as dysarthria or nystagmus; lasts minutes to hours and occurs daily to monthly
2) triggers: stress and alcohol
3) pathogenesis: mutation in CACN1A4 (same gene mutated in familial hemiplegic migraines and sometimes these patients’ have migraines during or outside ataxia attacks
4) txt: acetazolamide
Describe episodic ataxia III?
1) hereditary pattern?
2) presentation
3) txt
1) AD
2) p/w ataxia and tinnitus, vertigo; between attacks have myokymia
3) txt: acetazolamide
Describe episodic ataxia IV
1) presentation?
2) triggers?
1) ocular motion abnormalities triggered by head movements; unknown gene
Describe the layers of the cerebellum?
What is the main output to the deep cerebellar and vestibular n?
What is the only excitatory cell in the cerebellum?
outermost layer: molecular layer which consists of stellate and basket cells
middle layer: Purkinje cells (main output to deep cerebellar and vestibular n)
innermost layer = granular layer which consists of granule cells and Golgi interneurons. Granule cells - are the only excitatory cerebellar cell type
What is hyperekplexia?
Etiologies?
Pathophysiology?
Treatment?
- exaggerated startle; can present as sudden brief startle response or more prolonged tonic startle spasms with minor stimuli
- familial forms with mutations in the glycine receptor and prestnpatic glycine transporter; can be secondary to brainstem disorders, CJD or stiff person syndrome
- abnormal spinal Ia inhibitory interneuron reciprocal inhibition
How does cerebellar lesions result in ipsilateral signs?
inhibitory fibers from Purkinje cells of cerebellum –> deep cerebellar nuclei –> excitatory signal through the superior cerebellar peduncle –> decussate –> synapse in thalamus –> cortex –> corticobulbar and corticospinal tract which decussates again in the medullary pyramids
b/c fibers from the cerebellum to thalamus cross, and motor fibers from cortex cross again
What is the difference between stereotypies and complex motor tic?
Stereotypies are patterned, repetitive, stereotyped movements, or vocalizations that occur in response to an external or internal stimulus. (ie head nodding, arm flapping, body rocking, head banging, grunting, humming, or moaning)
-stereotypies are NOT associated with an urge and with relief like complex motor tics are
What genetic mutation is associated with PKD?
What mutations have been reported with PNKD?
Genetic mutations with PED? - CSF findings and txt?
PRRT2 gene in PKD
myofibrillogenesis regular (MR-1) with PNKD
GLUT-1 transporter gene with PED (CSF hypoglycorrhachia can be seen in PED, and ketogenic diet may help)
Autosomal dominant nocturnal frontal lobe epilepsy results from mutations in what receptor?
nicotinic acetylcholine receptor
