Pathology

Question 1

Alzheimer disease - what are risk factors for early onset Alzheimer’s?

Answer 1

Down syndrome (APP on chromosome 21), ApoE4 associated with increase risk (ApoE2 decreased risk), presenilin-1 and 2 also increase risk

Question 2

What are the gross findings of Alzheimer disease?

Answer 2

cortical atrophy - narrowing of gyri and widening of sulci, Decreased ACh

Question 3

What are the histological findings of Alzheimer disease?

Answer 3

extracellular Abeta amyloid plaques (senile plaques) in gray matter

Neurofibrillary tangles: intracellular, hyperphosphorylated tau protein

Question 4

What are the clinical features of Pick disease?

Answer 4

Frontotemporal dementia - spares parietal lobe and posterior 2/3 of superior temporal gyrus

Dementia, aphasia, parkinsonian aspects; change in personality

Question 5

What are the gross and histologic findings of Pick disease?

Answer 5

Frontotemporal atrophy, Pick bodies: spherical tau protein aggregates,

Question 6

What are the clinical features of Lewy body dementia? What is the defect?

Answer 6

dementia, hallucinations followed by parkinsonian features

Defect in alpha-synuclein (Lewy bodies, mostly cortical)

Question 7

What are the clinical findings of Creutzfeldt-Jakob disease?

Answer 7

Rapidly progressive dementia (weeks-months) with myoclonus “startle myoclonus”

Question 8

What are the histological findings in Creutzfeldt-Jakob disease?

Answer 8

Spongiform cortex, Prions PrPc -> PrPsc (beta-pleated sheet resistant to protease)

Question 9

What are the classic features of MS?

Answer 9

scanning speech, intention tremor, incontinence, INO, nystagmus

Question 10

What are the findings in MS?

Answer 10

Increased protein (IgG) in CSF and oligoclonal bands are diagnostic. Periventricular plaques on MRI (oligodendrocyte loss and reactive gliosis). multiple white matter lesions separated in time and space

Question 11

Acute inflammatory demyelinating polyradiculopathy (Guillain-Barre subtype) is associated with what infections?

Answer 11

Campylobacter jejuni, viral infections

Question 12

What is the mechanism of Acute inflammatory demyelinating polyradiculopathy (Guillain-Barre subtype)?

Answer 12

autoimmune destruction of Schwann cells -> demyelination of peripheral nerves -> symmetrical ascending paralysis and muscle weakness

Question 13

What are the findings for Acute inflammatory demyelinating polyradiculopathy (Guillain-Barre subtype)?

Answer 13

Increased CSF protein with normal cell count (albuminocytologic dissociation

Question 14

What can cause acute disseminated (postinfectious) encephalomyelitis?

Answer 14

Measles or VZV infections or some vaccinations - rabies, smallpox

Question 15

What is Charcot-Marie-Tooth disease?

Answer 15

aka Hereditary motor an sensory neuropathy (HMSN), Autosomal dominant. Defective proteins involved in structure and fxn of peripheral nerves or myelin sheath

Associated with scoliosis and foot deformities -> high or flat arches

Question 16

What enzyme is deficient in Krabbe disease?

Answer 16

Deficiency of galactocerebrosidase -> galactocerebroside and psychosine builds up and destroys myelin sheath

Question 17

What is the inheritance pattern and findings of Krabbe disease?

Answer 17

AR, findings: peripheral neuropathy, developmental delay, optic atrophy, globoid cells

Question 18

What is the deficiency in metachromatic leukodystrophy?

Answer 18

Most commonly arylsulfatase A deficiency -> build up of sulfatides -> impaired myelin sheath

Question 19

What are the findings and inheritance pattern for metachromatic leukodystrophy?

Answer 19

AR, Findings: central and peripheral demyelination with ataxia, dementia

Question 20

What is progressive multifocal leukoencephalopathy? What is it associated with?

Answer 20

Destruction of oligodendrocytes causes demyelination of CNS

Associated with JC virus, seen in 2-4% of AIDS patients as reactivation of latent viral infection
Increased risk associated with natalizumab, rituximab

Question 21

How does progressive multifocal leukoencephalopathy present?

Answer 21

Rapidly progressive, usually fatal

Question 22

What is adrenoleukodystrophy?

Answer 22

X-linked, Disrupts metabolism of VLCFAs -> buildup in nervous system, adrenals and testes. Progressive and can lead to coma/death and adrenal gland crisis

Question 23

What can cause peripheral vertigo?

Answer 23

Semicircular canal debris, vestibular nerve infection, Meniere disease)

Question 24

What causes central vertigo?

Answer 24

Brain stem or cerebellar lesions such as stroke affecting vestibular nuclei or posterior fossa tumor

Question 25

What are symptoms of peripheral vertigo?

Answer 25

delayed horizontal nystagmus

Question 26

What are symptoms of central vertigo?

Answer 26

Immediate nystagmus in any direction; may change direction. Skew deviation, diplopia, dysmetria

Question 27

Sturge-Weber syndrome

Answer 27

Congenital, NON-inherited

Activating mutation in GNAQ gene -> proliferation of blood vessels in the brain
Unilateral symptoms
Port-wine stain (nevus flammeus, CN V1/V2 distribution)
Ipsilateral leptomeningeal angioma -> seizures
Intellectual disability
Glaucoma
“Tram track calcifications”

Question 28

Tuberous sclerosis

Answer 28

Autosomal dominant. Hamartomas in CNS and skin; Angiofibromas, Mitral regurg, Ash-leaf spots, cardiac Rhabdomyoma, Mental retardation, renal Angiomyolipoma, Seizures, Shagreen patches

Increase incidence of subependymal astrocytomas and ungual fibromas

Question 29

Neurofibromatosis type I (von Recklinghausen disease)

Answer 29

Mutated NF1 tumor suppressor gene on chromosome 17 (inhibits RAS)

1. Pigmented lesions: Cafe-au-lait spots, axillary freckles (Crowe’s sign)
2. Lisch nodules (pigmented iris hamartomas),
3. cutaneous neurofibromas (contain Schwann cell proliferations),
   Also associated with: optic gliomas, pheochromocytomas

Question 30

von Hippel-Lindau disease

Answer 30

Hemangioblastomas (high vascularity w hyperchromatic nuclei) in retina, brain stem, cerebellum, spine; angiomatosis; bilateral renal cell carcinomas; pheochromocytomas

Question 31

Glioblastoma multiforme

Answer 31

most common primary brain tumor in adults

Can cross corpus callosum “butterfly glioma”
(+) GFAP stain - astroctyes
Histology: “pseudopalisading” pleomorphic tumor cells border central areas of necrosis and hemorrhage

Question 32

Meningioma

Answer 32

benign primary brain tumor

Arises from arachnoid cells, is external to brain parenchyma and may have dural attachment “tail”
Often asymptomatic, may have seizures
Histology: whorls and psammoma bodies

Question 33

Hemangioblastoma

Answer 33

Usually cerebellar
Associated with von Hippel-Lindau when found with retinal angiomas
Can produce EPO -> secondary polycythemia
Histology: closely arranged thin-walled capillaries

Question 34

Schwannoma

Answer 34

Usually at cerebellopontine angle
S-100 (+)
Usually localized to CN VIII -> vestibular schwannoma
Bilateral vestibular schwannomas in NF-2

Question 35

Oligodendroglioma

Answer 35

Frontal lobes, “chicken wire” capillary pattern

Histology: oligodendrocytes look like “fried eggs”

Question 36

Pituitary adenoma

Answer 36

Most commonly prolactinoma. Causes bitemporal hemianopia from compression of optic nerve and hyper or hypopituitarism

Question 37

Pilocytic astrocytoma

Answer 37

Children, benign tumor with good prognosis
Well circumscribed, most often found in posterior fossa (cerebellum)
GFAP (+)
Histology: Rosenthal fibers - eosinophilic corkscrew fibers

Question 38

Medulloblastoma

Answer 38

Found mostly in children; highly malignant cerebellar tumor. From primitive neuroectodermal origin.

Can compress 4th ventricle -> hydrocephalus
Can send “drop metastases” to spinal cord

Histology: Homer-Wright rosettes, small blue cells

Question 39

Ependymoma

Answer 39

Found mostly in children; usually in 4th ventricle, can cause hydrocephalus. poor prognosis

Histology: perivascular rosettes

Question 40

Craniopharyngioma

Answer 40

Benign childhood tumor. Often confused with pituitary adenoma bc both cause bitemporal hemianopia
Derived from remnants of Rathke pouch. Solid, cystic and calcification is common (tooth enamel like)