Chapter 28: CNS Flashcards
Differentiate hypoxia and ischemia
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
What are Charcot-Bouchard microaneurysms?
-small aneurysms developing as a result of hypertension in the basal ganglia
What syndromes are associated with Berry aneurysms?
- ADPKD
- Ehlers Danlos type IV
- NF1
- Marfan
- Fibromuscular dysplasia of extracranial arteries
- Coarctation of aorta
What organisms are seen in neonatal bacterial meningitis? What about adolescents? And the elderly?
Neonatal: group B strep, E coli
Adolescents: N. meningiditis
Elderly: S pneumo, Listeria
How does herpes affect the brain?
- encephalitis that is most severe in the inferior and medial temporal lobes
- necrotizing, hemorrhagic infection with perivascular inflammatory infiltrates
How does CMV affect the brain?
- paraventricular subependymal involvement
- necrotizing hemorrhagic ventriculoencephalitis and choroid plexitis
- most often immune suppressed person
What are features of HIV infection in the CNS?
- 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
Features of CNS toxoplasmosis?
- 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
What are the pathologic features of CJD?
- 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
What is fatal familial insomnia?
- 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
What is the pathogenesis of MS?
- Th1 and Th17 cells reacting against self myelin antigens
- HLA associations
What are macroscopic and microscopic features of MS?
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)
What are the histologic features of Alzheimer disease and what parts of the brain are most affected?
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
What is present in dopaminergic neurons in Parkinsons disease?
-alpha synuclein (Lewy bodies)
What is adrenoleukodystrophy?
- several forms, some X-linked
- myelin loss from CNS and PNS
- adrenal insufficiency
- inability to properly catabolize very long chain fatty acids within peroxisomes
What is Wernicke encephalopathy?
- 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
What are features of vitamin B12 deficiency in the CNS?
Myelin swelling with vacuolation
What neurons are affected first in hypoglycemia?
-Selective injury to large pyramidal neurons of cerebral cortex
What are toxic effects of carbon monoxide on the brain?
- selective injury to layers III and V of cerebral cortex, Sommer sector of hippocampus and Purkinje cells
- bilateral necrosis of globus pallidus
- later, demyelination
Where is methanol toxicity manifest?
- degeneration of retinal ganglion cells leading to blindness
- bilateral putamenal necrosis
What are histologic changes in the brain in ethanol toxicity?
- atrophy and loss of granule cells of cerebellar vermis
- later, loss of PUrkinje cells in the cerebellum and gliosis
What molecular alterations are most common in low grade astrocytomas?
p53 mutations
Overexpression of PDGFA and its receptor
What molecular alterations are assocated with the transition of a low grade to a higher grade glioma?
Disruption of RB and p16 as well as an 19q
What are features of primary glioblastoma?
- Older individuals
- More often amplification of MDM2 (which inhibits p53)
- More often mutations in EGFR genes
What is the significance of MGMT promoter methylation in GBM?
- 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
What genetic alterations are seen in medulloblastoma?
- loss of 17p: most common and associated with poor prognosis
- MYC amplification: associated with poor prognosis
What is the definition for atypical meningioma?
- 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
What cytogenetic abnormality is seen most commonly in meningioma?
-NF2 loss (22q12): b oth sporadic and syndromic
What is the function of NF1?
Neurofibromin stimulates the activity of a GTPase that inhibits RAS activity
What is the function of NF2?
Merlin is a structural cytoskeletal protein that may regulate membrane receptor signalling and inhibit growth
What are clinical features of NF2?
Bilateral 8th nerve schwannomas
Multiple meningiomas
Gliomas, typically spinal cord ependymomas
Must less common than NF1
What is the function of TSC1 and TSC2?
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
What are clinical features of tuberous sclerosis?
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
What are clinical features of VHL?
Hemangioblastomas especially of cerebellum and retina
Cysts of pancreas, liver, kidneys
Renal cell carcinoma
Pheochromcytoma
What is the function of VHL (3p25)
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
