Dr. Cheng's board review

Question 1

Which neurodegenerative diseases are synucleinopathies?

Answer 1

Parkinson’s disease MSA dementia with Lewy bodies

Question 2

Which neurodegenerative diseases are tauopathies?

Answer 2

Progressive supranuclear palsy Frontotemporal dementia corticobasal ganglionic degeneration

Question 3

How does a DaTscan work?

Answer 3

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

Question 4

What are the group of disorders called neurodegeneration with brain iron accumulation (NBIA)?

Answer 4

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

Question 5

What is pantothenate-kinase associated neurodegeneration?

Answer 5

PKAN; most common type of NBIA -due to mutations in patothenate kinase 2 gene -MRI with “eye of the tiger” is suggestive of dx

Question 6

Cerebrotendinous Xanthomatosis: (1) pathophysiology (2) presentation (3) MRI/lab findings (4) treatment

Answer 6

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

Question 7

Describe the frequency seen in orthostatic tremor?

Answer 7

High frequency 14-16 Hz affecting the trunk and thighs

Question 8

Striopallidodentate calcinosis: (1) pathophysiology (2) etiologies (2) presentation

Answer 8

(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

Question 9

draw out the metabolism of L-DOPA

Answer 9

Question 10

Ataxia Telangiectasia

1) presents with:
2) pathophysiology
3) labs

Answer 10

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

Question 11

The Spinocerebellar Ataxia

1) pathophysiology
2) p/w
3) MRI

Answer 11

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

Question 12

Fragile X tremor-ataxia synrome

1) pathophysiology:
2) p/w:
3) MRI:

Answer 12

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

Question 13

Workup for acquired ataxia?

Answer 13

check TSH (hypothyroidism); Miller-Fisher variant; post-infectious (varicella zoster)

medication exposures: chemo, salicylates, toluene, bismuth, phenytoin

infections: HIV, CJD, Whipple’s disease

Question 14

Freidreich’s ataxia

1) genetic defect:
2) p/w:

Answer 14

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

Question 15

Describe episodic ataxia type 1:

1) presentation?
2) triggers
3) pathogenesis
4) txt

Answer 15

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

Question 16

Describe episodic ataxia II?

1) presentation
2) triggers
3) pathogenesis:
4) txt:

Answer 16

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

Question 17

Describe episodic ataxia III?

1) hereditary pattern?
2) presentation
3) txt

Answer 17

1) AD
2) p/w ataxia and tinnitus, vertigo; between attacks have myokymia
3) txt: acetazolamide

Question 18

Describe episodic ataxia IV

1) presentation?
2) triggers?

Answer 18

1) ocular motion abnormalities triggered by head movements; unknown gene

Question 19

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?

Answer 19

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

Question 20

What is hyperekplexia?

Etiologies?

Pathophysiology?

Treatment?

Answer 20

• 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

Question 21

How does cerebellar lesions result in ipsilateral signs?

Answer 21

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

Question 22

What is the difference between stereotypies and complex motor tic?

Answer 22

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

Question 23

What genetic mutation is associated with PKD?

What mutations have been reported with PNKD?

Genetic mutations with PED? - CSF findings and txt?

Answer 23

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)

Question 24

Autosomal dominant nocturnal frontal lobe epilepsy results from mutations in what receptor?

Answer 24

nicotinic acetylcholine receptor

Question 25

When palatal myoclonus results from a brainstem lesion, what is the pathophysiology thought to be?

What can be seen on MRI?

Answer 25

dysfunction of the pathways connecting the dentate nucleus, the inferior olive, and red nucleus (Guillain Mollaret triangle)

-hypertrophy of the inferior olive may be seen on MRI (due to overactivation)

Question 26

Describe the Guillain-Mollaret triangle. Lesions in this pathway can present with?

Answer 26

The Guillain–Mollaret triangle comprises the ipsilateral red nucleus in the midbrain, the inferior olive in the medulla and the contralateral dentate nucleus in the cerebellum: together, these form the dentato-rubro-olivary pathway. Pathology in this triangle disinhibits (and so activates) the inferior olivary nucleus. The olivary nucleus then hypertrophies and its rhythmical discharges may manifest clinically as oculopalatal tremor

Question 27

Most common hereditary form of dopa responsive dystonia?

Answer 27

mutation in GTP cyclohydrolase I on chr 14 (DTY 5)

GCH 1 is the rate limiting enzyme in tetrahydrobiopterin synthesis, which is a cofactor for tyrosine hydroxylase (enzyme that catalyzes the rate-limiting step of dopamine synthesis)

Question 28

1) What is myoclonus?
2) What is cortical myoclonus?
3) Where else can myoclonus originate from?

Answer 28

1) brief, sudden, jerky movement that may be generalized, multifocal, or segmental
2) myoclonus that results from from abnormal activity in the sensorimotor cortex
3) subcortical, brainstem, spinal cord (which typically results in segmental myoclonus), or propriospinal; nerve root or peripheral lesions rarely result in myoclonus

Question 29

1) How does Wilson’s disease present? (6)
2) lab/MRI findings
3) treatments? (4)

Answer 29

1) presents with abnormal movements (parkinsonism, dystonia, tremor, ataxia); wing beating tremor; characteristic grin/drooling; psych sx (depression, anxiety, psychosis); hepatic failure; Kayser-Fleischer rings
2) decreased ceruloplasmin; increased urinary copper excretion
3) txt: D-penicillamine; trientine dihydrochloride; zinc supplementation (binds copper in the gut, prevention absorption); low copper diet (avoid nuts, chocolate, shellfish)

Question 30

1) What is Tourette’s syndrome? Age of onset?
2) Associated psychiatric conditions? (5)
3) pathophysiology
4) Txt? (3)

Answer 30

1) diagnosed in the setting of at least one motor and one phonic tic that occur beginning prior to age 18
2) associated psych conditions: ADHD, OCD, anxiety, depression, impulse control disorders
3) pathophys: thought to involve dopaminergic hyper-stimulation of the ventral striatum and limbic system
4) txt: habit reversal therapy; antidopaminergic agents ie haloperidol, pimozide, atypical antipsychotics; clonidine is useful for ADHD/behavioral component

Question 31

What heavy metal toxicity can lead to parkisonism and how does it present?

Answer 31

Manganese; presents with Manganese madness, parkinsonism (but usually without tremor), cock walk (toe walking with elbow flexion)

Question 32

What is the frequency of ET vs enhanced physiologic tremor?

Answer 32

ET: 4-8 Hz

enhanced physiologic tremor: 7 to 12 Hz

Question 33

Treatment of medically refractory essential tremor, DBS can be used at what location?

Answer 33

ventral intermediate nucleus (VIM) of the thalamus

Question 34

What is a rubral tremor?

• where does it localize to?
• associated with what dx?

Answer 34

1) low frequency tremor present at rest, with posture, and with action
2) lesion in the dentate nucleus of the cerebellum and/or superior cerebellar peduncle
3) often seen in MS

Question 35

1) CBS presents with (8)?
2) Classic etiology/pathophysiology?

Answer 35

1) It’s a parkinson’s plus syndrome that presents with focal limb rigidity/dystonia; cortical myoclonus; asterognosis; agraphesthesia; cognitive dysfunction (frontal lobe pattern); apraxia; alien limb phenomenon; parkinsonian features (ie rest tremor, rigidity, and bradykinesia)
2) corticobasal gangiolonic degeneration (deposition of phosphorylated tau and neuronal degeneration in pre- and postcentral cortical areas, BG, thalamus, substantia nigra

Question 36

DBS is effective for which symptoms of PD? Name three targets in the brain?

Answer 36

Tremor and bradykinesia (NOT effective for levodopa unresponsive gait freezing, falls, or other axial sx)

targets: STN, GPi, VIM

Question 37

Frequency of tremor in PD?

Answer 37

Moderate freq 4-6 haha, distal rather than proximal