Chapter 28: CNS

Question 1

Differentiate hypoxia and ischemia

Answer 1

Hypoxia: low partial pressure of oxygen, or impairment of blood’s oxygen carrying capacity or inhibition of oxygen use in tissue

Ischemia: interruption of normal circulatory flow either from hypotension or obstruction

Question 2

What are Charcot-Bouchard microaneurysms?

Answer 2

-small aneurysms developing as a result of hypertension in the basal ganglia

Question 3

What syndromes are associated with Berry aneurysms?

Answer 3

• ADPKD
• Ehlers Danlos type IV
• NF1
• Marfan
• Fibromuscular dysplasia of extracranial arteries
• Coarctation of aorta

Question 4

What organisms are seen in neonatal bacterial meningitis? What about adolescents? And the elderly?

Answer 4

Neonatal: group B strep, E coli

Adolescents: N. meningiditis

Elderly: S pneumo, Listeria

Question 5

How does herpes affect the brain?

Answer 5

• encephalitis that is most severe in the inferior and medial temporal lobes
• necrotizing, hemorrhagic infection with perivascular inflammatory infiltrates

Question 6

How does CMV affect the brain?

Answer 6

• paraventricular subependymal involvement
• necrotizing hemorrhagic ventriculoencephalitis and choroid plexitis
• most often immune suppressed person

Question 7

What are features of HIV infection in the CNS?

Answer 7

• HIV encephalitis: widespread microglial nodules with multinucleated giant cells often associated with tissue necrosis or gliosis
• White matter disease with multifocal areas of myelin pallor, axonal swelling and gliosis

Question 8

Features of CNS toxoplasmosis?

Answer 8

• usually immunosuppressed (especially HIV)
• multiple ring-enhancing lesions near the gray-white junction
• necrosis, petechial hemorrhage, with free tachyzoites and encysted bradyzoites at the periphery
• organisms stain with Giemsa or IHC

Question 9

What are the pathologic features of CJD?

Answer 9

• spongiform transformation of cortex and deep gray structures
• Later stages may have neuronal lossa nd reactive gliosis
• Kuru plaques: extracellular deposits of aggregated abnormal protein that are Congo Red and PAS positive and most often occur in the cerebellum

Question 10

What is fatal familial insomnia?

Answer 10

• caused by a PRNP mutation
• results in ataxia and eventually coma
• does not have spongiform pathology but instead neuronal loss and gliosis most marked in the thalamus

Question 11

What is the pathogenesis of MS?

Answer 11

• Th1 and Th17 cells reacting against self myelin antigens
• HLA associations

Question 12

What are macroscopic and microscopic features of MS?

Answer 12

Macroscopic: well-circumscribed gray-tan plaques often adjacent to lateral ventricles, also around optic nerves, brainstem, cerebellum

Microscopic: active plaques have abundant myelin-engulfing macrophages; inactive plaques have a reduction in oligodendrocyte nuclei and astrocyte proliferation and gliosis

-lesions of varying ages (unlike in ADEM)

Question 13

What are the histologic features of Alzheimer disease and what parts of the brain are most affected?

Answer 13

Neuritic plaques: collections of dystrophic neurites around a central amyloid core which stain with Congo Red and are found in hippocampus, amygdala and neocortex; a-beta is found; more specific than tangles

Neurofibrillary tangles: bundles of filaments with a flame shape that are positive for silver staining and made up of hyperphosphorylated tau protein (a microtubule associated protein); found in entorhinal cortex, hippocampus, amygdala

Question 14

What is present in dopaminergic neurons in Parkinsons disease?

Answer 14

-alpha synuclein (Lewy bodies)

Question 15

What is adrenoleukodystrophy?

Answer 15

• several forms, some X-linked
• myelin loss from CNS and PNS
• adrenal insufficiency
• inability to properly catabolize very long chain fatty acids within peroxisomes

Question 16

What is Wernicke encephalopathy?

Answer 16

• psychotic symptoms and ophthalmoplegia that develops in thiamine deficiency
• foci of hemorrharge and necrosis in the mamillary bodies and the walls of the 3rd and 4th ventricles

Question 17

What are features of vitamin B12 deficiency in the CNS?

Answer 17

Myelin swelling with vacuolation

Question 18

What neurons are affected first in hypoglycemia?

Answer 18

-Selective injury to large pyramidal neurons of cerebral cortex

Question 19

What are toxic effects of carbon monoxide on the brain?

Answer 19

• selective injury to layers III and V of cerebral cortex, Sommer sector of hippocampus and Purkinje cells
• bilateral necrosis of globus pallidus
• later, demyelination

Question 20

Where is methanol toxicity manifest?

Answer 20

• degeneration of retinal ganglion cells leading to blindness
• bilateral putamenal necrosis

Question 21

What are histologic changes in the brain in ethanol toxicity?

Answer 21

• atrophy and loss of granule cells of cerebellar vermis
• later, loss of PUrkinje cells in the cerebellum and gliosis

Question 22

What molecular alterations are most common in low grade astrocytomas?

Answer 22

p53 mutations

Overexpression of PDGFA and its receptor

Question 23

What molecular alterations are assocated with the transition of a low grade to a higher grade glioma?

Answer 23

Disruption of RB and p16 as well as an 19q

Question 24

What are features of primary glioblastoma?

Answer 24

• Older individuals
• More often amplification of MDM2 (which inhibits p53)
• More often mutations in EGFR genes

Question 25

What is the significance of MGMT promoter methylation in GBM?

Answer 25

- Predicts responsiveness to alkylating agents - MGMT required for repair of chemo induced damage so those that are silenced by methylation will respond better to treatment because they can't repair the damage

Question 26

What genetic alterations are seen in medulloblastoma?

Answer 26

- loss of 17p: most common and associated with poor prognosis - MYC amplification: associated with poor prognosis

Question 27

What is the definition for atypical meningioma?

Answer 27

- 4 or more mitoses/10 high power field - 3 of: increased cellularity, small cell change, prominent nucleoli, patternless growth, spontaneous necrosis - clear cell and chordoid patterns

Question 28

What cytogenetic abnormality is seen most commonly in meningioma?

Answer 28

-NF2 loss (22q12): b oth sporadic and syndromic

Question 29

What is the function of NF1?

Answer 29

Neurofibromin stimulates the activity of a GTPase that inhibits RAS activity

Question 30

What is the function of NF2?

Answer 30

Merlin is a structural cytoskeletal protein that may regulate membrane receptor signalling and inhibit growth

Question 31

What are clinical features of NF2?

Answer 31

Bilateral 8th nerve schwannomas Multiple meningiomas Gliomas, typically spinal cord ependymomas Must less common than NF1

Question 32

What is the function of TSC1 and TSC2?

Answer 32

Hamartin (9q34) and Tuberin (16p13) - both proteins form a complex that inhibits mTOR which is a key regulator of protein synthesis - mTOR controls cell size, which may be why tumors in TS have abundant cytoplasm

Question 33

What are clinical features of tuberous sclerosis?

Answer 33

Cortical subers and subependymal nodules Subependymal giant cell astrocytomas Epilepsy from tubers Renal angiomyolipomas Retinal glial hamartomas Cysts of liver, kidneys and pancreas Pulmonary LAM Cardiac rhabdomyomas Angiofibromas Shagreen patche Ash-leaf hypopigmented patches Subungual fibromas

Question 34

What are clinical features of VHL?

Answer 34

Hemangioblastomas especially of cerebellum and retina Cysts of pancreas, liver, kidneys Renal cell carcinoma Pheochromcytoma

Question 35

What is the function of VHL (3p25)

Answer 35

Component of a ubiquitin ligase complex that downregulates HIF1 HIF1 normally regulates expression of VEGF, erythropoeitin, etc Dysregulation of erythropoietin is responsible for polycythemia seen in hemangioblastomas