CNS ch. 22

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• Acute neuronal injury becomes evident within 12h of an irreversible hypoxic-ischemic insult
• changes in cell body of neurons during injury shrinkage, loss of Nissl substance (body), Axonal injury causes → enlargement, rounding
• changes in nucleus of neurons during injury pyknosis, disappearance of the nucleolus, assumes the angulated shape of the shrunken cell body. Axonal injury causes → peripheral displacement of the nucleus, enlargm. of nucleolus & peripheral dispersion of Nissl substance (central chromatolysis)
• changes in cytoplasm of neurons during injury eosinophilia
• changes in axons of neurons during injury swollen (from spheroids), disruption of transport
• changes in BBB of neurons during injury breakdown
• changes in neurons during Alzheimer's disease tangles (intracellular inclusion)
• changes in neurons during parkinson's lewy bodies (intracellular inclusion)
• changes In other neurodegenerative diseases (injury) dystrophic neurites (thickened & tortuous neuronal processes)
• changes in neurons during injury accumulate complex lipids (lipofuscin) in their cytoplasm & lysosomes.
• gliosis (by astrocytes) repair and scar formation
• In long- standing gliosis the cytoplasm of reactive astrocytes shrinks & the cellular processes become more tightly interwoven forming a ⇒ fibrillary astrocytes
• Gemistocytic astrocyte Cell extends multiple stout, ramifying processes
• Rosenthal fibers thick, elongated, brightly eosinophilic protein aggregates found in astrocytic processes in chronic gliosis & in some low-grade gliomas.
• In progressive multifocal leukoencephalopathy you can see viral inclusions in them, w/ a smudgy, homogeneous- appearing enlarged nucleus.
• microglial cells during injury develop elongated nuclei (rod cells)
• Microglial nodules aggregates of elongated microglial cells at sites of tissue injury
• Central neurocytoma A low-grade neoplasm characterized by evenly spaced, round, uniform nuclei & often islands of neuropil
• Gangliomas Tumors with a mixture of glial elements (a low-grade astrocytoma, mature-appearing neurons) that usually is slow-growing – but the glial component occasionally becomes frankly anaplastic ⇒ the disease then progresses rapidly to seuizures
• Dysembryoplastic neuroepithelial tumor A distinctive, low-grade childhood tumor that grows slowly and carries a relatively good prognosis after resection
• Morphology of Dysembryoplastic neuroepithelial tumor small round neuronal cells arranged in columns and around central cores of processes, Form multiple discrete intracortical nodules that have a myxoid background, well-differentiated “floating” neurons within pools of mucopolysaccharide-rich myxoid fluid seen
• EMBRYONAL (PRIMITIVE) NEOPLASMS Some tumors of neuroectodermal origin have a primitive “small round cell” appearance”
• NEURONAL TUMORS in csn Central neurocytoma, ganglioma, Dysembryoplastic neuroepithelial tumor
• Primary Central Nervous System Lymphoma Occurs mostly as diffuse large B cell lymphomas and is agressive w/ poor response to chemo, seen in people with EBV & immunosupression
• germ cell tumor Account for 0.2% to 1% of brain tumors in people of European descent – but 10% of brain tumors in persons of Japanese ethnicity, its a tumor of the young (occuring first 2 decades of life)
• medulloblastoma most common embryonal (primitive) neoplasm
• Medulloblastoma tumor located in the cerebellum accounting for 20 % of pediatric tumors, can be found as PNETs in other body parts
• genes involved in medulloblastoma MYC amplification, WNT signaling pathway , Mutation activation the sonic (SHH) pathway
• morphology of medulloblastoma "small blue", Focal neuronal differentiation – seen in the form of the Homer Wright or neuroblastic rosette ( resembles the rosettes in neuroblastomas) OBS❗ characterized by primitive tumor cells surrounding central neuropil (delicate pink material formed by neuronal processes).
• MENINGIOMAS Arise from arachnoid meningothelial cells & are often attached to the dura
• pathogenesis of menigiomas Neurofibromatosis type 2 (NF2 ) & Acquired loss-of-function mutation in NF2
• Grade 1 meningiomas Psammomatous, Syncytial, Secretory, Fibroblastic
• grade 2 meningiomas pattern-less growth
• Grade 3 meningiomas May resemble a high- grade sarcoma or carcinoma – although there usually is some histologic evidence of a meningothelial cell origin.
• Some of the more common patterns in metatstatic tumors include Subacute cerebellar degeneration, Limbic encephalitis, Subacute sensory neuropathy, Syndrome of rapid-onset psychosis, catatonia, epilepsy & coma
• Subacute cerebellar degeneration (in metastatatic tumors) ataxia, with destruction of Purkinje cells, gliosis, and a mild inflammatory infiltrate
• Limbic encephalitis (in metastatatic tumors) a subacute dementia, with perivascular inflammatory cells, microglial nodules, some neuronal loss & gliosis (all centered in the medial temporal lobe)
• Subacute sensory neuropathy (in metastatatic tumors) leads to altered pain sensation, with loss of sensory neurons from dorsal root ganglia, in association with inflammation
• Syndrome of rapid-onset psychosis, catatonia, epilepsy & coma ((in metastatatic tumors) assoc. w/ ovarian teratoma and antibodies against the N-methyl-D-aspartate (NMDA) receptor
• TUBEROUS SCLEROSIS An autosomal dominant syndrome Characterized by: the development of hamartomas & benign neoplasms – involving the brain and other tissues.
• CNS tumors have ”D-A-M-P " Dangerous, Anatomic site, Metastasis, Premalignant lesions
• Most CSN tumor is children are located in posterior fossa
• Most CNS tumors in adults are located in supratentorial areas
• Breast, lung, skin (melanoma), kidneys, GI are common primary sites for Metastatic tumor of CNS
• mutations in 1ary diffuse astrocytoma Glioblastoma inclued TERT, EGFR and morphology is Necrosis”(neoplastic), “ cystic degeneration”, “hemorrhage”,“snake-like pattern”.
• Mutations in Diffuse astrocytoma (secondary) – grade II, anaplastic & glioblastoma include p53, ATRX, IDH1, IDH2 and morphologies include cystic degeneneration.
• Mutations in Diffuse astrocytoma of children include MYC, BRAF
• Mutations in Pilocytic astrocytoma includes BRAF and finding include "“ hair-like” & “ischemic necrosis”
• Mutations in Oligodendroglioma includes Deletions of CH. 1p & 19q
• Mutations in ependymoma includes merlin gene since it is a part of NF2.
• Medulloblastoma is a “ small round blue cell tumor” with mutations of WNT pathway and SHH pathway which inlude MYCN, GLI1, GLI2
• Mutations in Meningiomas include Merlin gene, loss of function on ch. 22 and psammoma bodes can be found in one the subtypes
• Subacute cerebellar degeneration Occurs in metastatic tumors and is ataxia, with destruction of Purkinje cells, gliosis, and a mild inflammatory infiltrate
• Limbic encephalitis Occurs in metastatic tumors and is a subacute dementia, with perivascular inflammatory cells, microglial nodules, some neuronal loss & gliosis (all centered in the medial temporal lobe)
• Subacute sensory neuropathy Occurs in metastatic tumors and leads to altered pain sensation, with loss of sensory neurons from dorsal root ganglia, in association with inflammation
• Syndrome of rapid-onset psychosis, catatonia, epilepsy & coma Occurs in metastatic tumors and is assoc. w/ ovarian teratoma and antibodies against the N-methyl-D-aspartate (NMDA) receptor
• Many hemangiomas forming could indicate in the person having tuberous sclerosis which is an autosomal dominant famililal syndrome a familial tumor syndrome where TSC 1 & TSC2 genes are mutated .
• Many hemangioblastomas, cysts and Renal cell carcinomas forming could indicate Von-hippel lindau disease associated with VHL mutation.
• types of cerebral edema vasogenic & cytotoxic
• types of hydrocephalus communicating & noncommunicating
• Types of herniations subfalcine, transtentorial, tonsillar
• False localizing sign occurs in transtentorial herniation – if the amount of displaced temporal lobe is large enough, the pressure on the midbrain can compress the contralateral cerebral peduncle against the tentorium ⇒ results in hemiparesis ipsilateral to the side of the herniation.
• Kernohan’s notch occurs in Transtentorial (uncinate) herniation – deformity created by the compress. of the peduncle
• Duret hemorrhages progression of transtentorial herniation often accomp. by linear or flame-shaped hemorrh. in the midbrain & pons
• Area/cells mostly susceptible to global cerebral ischemia is pyramidal cells in the hippocampus and neocortex AND purkinje cells of cerebellum.
• The subtypes of ischemia are: Global & focal cerebral ischemia
• Predisposing factors for embolic infract it is a focal cerebral ischemia – by myocardial dysfunction, valvular disease & atrial fibrillation
• Area mostly affected by embolic infarcts include middle cerebral artery
• the worst headache I’ve ever had" subarachnoid hemorrhage
• Most common cause of clinically significant nontraumatic subarachnoid hemorrhage include berry (saccular) aneurysm Occuring over time because of a weakned tunica media
• Except for berry other types of aneurysms therosclerotic (fusiform & inv. basilar a), mycotic, traumatic, dissecting
• Primary angiitis of the CNS a form of vasculitis involving multiple small to medium- sized parenchymal & subarachnoid vessels – that is characterized by chronic inflammation, multinucleate giant cells (with or without granuloma formation), & destruction of vessel wall Affected persons present with a diffuse encephalopathy, often with cognitive dysfunction.
• chronic traumatic encephalopathy A trauma-associated degeneration which is characterized by a unique pattern of intraneuronal tau protein inclusions
• Most frequent type of CNS malformation includes neural tube defect
• asymptomatic bone defect asymptomatic bone defect
• Myelomeningocele an extension of CNS tissue thru a defect in the vertebral column – occuring most commonly in the lumbosacral region & leads to patients having motor & sensory deficits in the lower extremities & problems with bowel and bladder control.
• Anencephaly a malformation of the anterior end of the neural tube that leads to the absence of the brain and the top of skull
• Encephalocele a diverticulum of malformed CNS tissue extending through a defect in the cranium. It most often involves the occipital region or the posterior fossa. When it occurs anteriorly, brain tissue can extend into the sinuses.
• causes of microencephaly chromosome abnormalities, fetal alcohol syndrome, and human immunodeficiency virus type 1 (HIV-1) infection acquired in utero
• Lissencephaly agyria
• pachygyria patchy involvement of gyri
• bumpy or cobblestone-like surface Polymicrogyria
• The Arnold-Chiari malformation a small posterior fossa w/ a misshapen midline cerebellum & downward extension of the vermis through the foramen magnum
• Dandy-Walker malformation missing cerebellar tissue
• Joubert syndrome absence of the vermis and brain stem abnormalities resulting in eye movement problems and disrupted respiratory patterns
• “Active” plaques in MS Type 1 → has macrophage infiltrates with sharp margins Type 2 → similar to 1, but also shows complement deposition (suggesting antibody-mediated component) Type 3 → less well-defined borders & oligodendrocyte apoptosis Type 4 → non apoptotic oligodendrocyte loss.
• beri beri thiamine deficiency leading to Wernicke-Korsakoff syndrome
• First area affected by parkinson's disease is medulla
• Lewy body dementia (LBD) when the parkinsson's arises within 1 year of the onset of motor symptoms
• mutations in Parkinson’s disease PARK7, PINK1, LRRK2,
• mutations in Huntington disease CAG trinucleotide repeat expansion in 4p16.3
• mutations in Spinocerebellar ataxia CAG trinucleotide repeat
• otitis media, upper lip furuncle, skull fracture, staphylococcal sinusitis, acute bacterial endocarditis, cyanotic congenital heart disease, chronic pulmonary infections brain abscess

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