Nervous System Flashcards
Acute neuronal injury becomes evident on routine H&E staining within __ hr/s of an irreversible hypoxic/ischemic insult
12h
Manifestations of acute neuronal injury
- Shrinkage of cell body
- Disappearance of the nucleolus
- Intense eosinophilia of the cytoplasm
(“red nucleus”) - Loss of NIssl substance
Neuronal processes become thickened and tortuous in some neurodegenerative diseases
Dystrophic neurites
Principal cells responsible for repair and scar formation in the brain
Astrocytes (hyperplasia and hypertrophy)
Degenerative change in astrocytes; round, faintly basophilic PAS(+) concentrically lamellate aggregates of polyglucosans
Corpora amylacea
This virus preferentially infects:
A. Oligodendroglioma
B. Ependymal cell
A. JC virus (progressive multifocal leukoencephalopathy)
B. CMV (congenital CMV)
Macrophages develop elongated nuclei in neurosyphilis or other infections
Rod cells
The brain accounts for only 1-2 of the body weight but receives __% of the resting cardiac output; and accounts for __% of the total body oxygen consumption.
15% of CO
20% of total O2 consumed
Widespread ischemic/hypoxic injury occurs when there is a generalized reduction of cerebral perfusion. This occurs with systolic pressure < ____.
Global cerebral ischemia.
<50 mmHg
Areas of the brain MOST susceptible to ischemia of short duration
- Pyramidal cells of the Sommer sector (CA1) of the hippocampus
- Purkinje cells of the cerebellum
- Pyramidal neurons in the neuronal cortex
In the cerebral cortex the neuronal loss and gliosis produce an uneven destruction of the neocortex, with preservation of some layers and involvement of tohers.
Pseudolaminar necrosis
In the cerebral hermispheres, the border zone between the _____ distributions is at greatest risk for watershed infacts.
MCA and ACA
The territory of distribution of the ____ - the direct extension of the ICA - is most frequently affected by embolic infarction.
MCA
The most common sites of primary thrombosis in the cerebral vasculature.
- Carotid bifurcation
- Origin of the MCA
- Either end of the basilar a.
Tissue liquefaction after brain infarct occurs ___ after injury
10 days to 3 weeks
The gliotic layer of tissue that delimits the cavity from the meninges and subarachnoid space, developing several months after an infarct, is derived from:
Molecular layer fo the cortex
Hypertensive intraparenchymal hemorrhages typically occur in the:
- Basal ganglia
- Thalamus
- Pons
- Cerebellum
Cerebral amyloid angiopathy is a disease in which amyloidogenic peptides deposit in these vessels leading to ___ hemorrhages.
Leptomeningel and cortical
(sparing of the vasculature of the white matter and deep gray structures).
Lobar hemorrhages
Most frequent cause of clinically significant subarachnoid hemorrhage
Saccular aneurysm (Robbins) Trauma! (Greenberg)
Overall, cerebral aneurysms have a roughly ___% per year rate of bleeding
1.3%
Most common locations of saccular aneurysms
AComm (40%)
MCA (34%)
ICA-MCA (20%)
PCA (4%)
The sac of saccular cerebral aneurysms is made up of
Thickened hyalinized intima.
Absent muscular wall and intimal elastic lamina
Most common vascular malformation in the brain
AVM
Differentiate cavernous from capillary hemangiomas in the brain.
Both are dilated, thin-walled vascular channels. Cavernous hemangiomas are devoid of intervenous nervous tissue (with low flow; no arteriovenous shunting); while capillary telangiectasias are separated by relatively normal brain parenchyma.
Most common location of capillary hemangioma
Pons
Most common location of cavernous hemangioma
Cereberellum
Pons
Subcortical regions
Differentiate cavernous from capillary hemangiomas in the brain.
Both are dilated, thin-walled vascular channels. Cavernous hemangiomas are devoid of intervenous nervous tissue (with low flow; no arteriovenous shunting); while capillary telangiectasias are separated by relatively normal brain parenchyma.
Most common location of capillary hemangioma
Pons
Most common location of cavernous hemangioma
Cereberellum
Pons
Subcortical regions
Lacunar infarcts are arbitrarily defined as small infarcts <___mm wide.
15
Inflammatory disorder that involves multiple small to medium-sized parenchymal and subarachnoid vessels; characterized by chronic inflammation, and multinucleated giant cells. Affected individuals develop diffuse encephalopathy. Treatment?
Primary angiitis of the CNS.
Treat with steroids.
Most common location of contusions
Frontal lobes along the orbital gyri
Temporal lobes
T/F. In brain trauma, superficial layers of the brain are preserved and gliotic.
False. Superficial layers are most severely affected. Statement is true for infarcts.
Area of the spinal cord most often affected by syringomyelia
Cervical spinal cord
Large cystic lesions develop throughout the hemispheres after severe perinatal infarcts of the brain
Multicystic encephalopathy
Most common route of entry of infections to the brain
Hematogenous spread
Most common cause of bacterial meningitis:
- In adolescents and young adults
- In neonates
- In elderly
- Neisseria meningitidis
- Group B strep / E coli
- Listeria monocytogenes / S pneumoniae
T/F. TB meningitis is characterized by pleiocytosis with mononuclear predominance, markedly elevated CHON, and markedly low CHO.
False. CHO is only moderately reduced or even normal.
In progressive multifocal leukoencephalopathy, the virus infects ___ leading to bizarre giant forms with irregular, hyperchromatic nuclei that can be mistaken for tumor
Astrocytes
Although JC virus preferentially infects oligos, it can also infect astrocytes.
Most common pattern of involvement of CMV CNS infection in the immunosuppressed patient
Subacute encephalitis.
CMV localizes to the paraventricular subependymal regions leading to hemorrhagic necrotizing ventriculoencephalitis and choroid plexitis
Neurologic dysfunction in AIDS occurs in ___% of patients. What are the three patterns of direct injury?
60%.
- Aseptic HIV meningitis (occurs within 1-2 weeks of seroconversion in 10%)
- AIDS-dementia complex
- Vacuolar myelopathy (resemble SCID although vitamin B12 levels are normal.)
What is the fungal agent causing encephalitis in the following scenarios:
- Multiple microabscesses
- Spreads by direct extension; esp in DKA patients
- Widespread septic hemorrhagic infarcts
- Candida albicans
- Mucor
- Aspergillus fumigatus
Multiple ring-enhancing lesions seen on cranial CT of a patient with AIDS is most likely:
Cerebral toxoplasmosis
T/F. In Creutzfeldt-Jakob Disease, the pathognomonic finding is a spongiform transformation of the cerebral cortex and deep gray matter structures. There is severe neuronal loss, reactive gliosis, and marked inflammatory infiltrates.
False!
NO inflammatory infiltrates!
This accounts for about 80% of adult primary brain tumors.
Fibrillary astrocytoma
Fibrillary astrocytoma is classified into (3):
- Astrocytoma
- Anaplastic astrocytoma
- Glioblastoma multiforme
Mean survival for patients with GBM
8 to 10 months
Characteristic histologic features of GBM
- Necrosis
- Vascular or endothelial proliferation
- Pseudopalisading nuclei
Histology of a brain mass reveals bipolar cells with long thin hairlike processes that are GFAP positive; Rosenthal fibers, eosinophilic granular bodies, and microcysts. Necrosis and mitoses are absent.
Pilocytic astrocytoma
Histology of a brain mass revels sheets of regular cells with spherical nuclei containing finely granular chromatid surrounded by a clear halo of cytoplasm; delicate network of anastomosing capillaries; (+) calcification.
Oligodendroglioma
“Fried egg” “Chicken wire”
Most common location of ependymomas in adults
Spinal cord
This brain tumor consists of small round cells with features of neurons arranged in columns and around central cores of processes; form intracortical nodules that have a myxoid background.
Common in childhood; in the superficial temporal lobe
Dysembryoplastic neuroepithelial tumor
Central nuerocytoma is found within and adjacent to the ventricular system, most commonly the:
Lateral or third ventricles
Most common CNS neoplasm in immunosuppresed individuals. In these individuals, the lesion is caused by infection with ___.
CNS lymphomas
EBV
Meningiomas arise from the ___
Meningothelial cell of the arachnoid
Top 5 most common primary sites of brain metasases
- Lung
- Breast
- Skin
- Kidney
- GI
Paraneoplastic syndromes involving the CNS and PNS are most commonly due to:
Small cell Ca of the lung
Which CNS paraneoplastic syndrome is described:
- Altered pain sensation, with loss of sensory neurons from the DRG
- Subacute dementia, perivascular inflammatory cuffs and gliosis centered around the medial temporal lobe.
- Ataxia, destruction of Purkinje cells
- Subacute sensory neuropathy
- Limbic encephalitis
- Subacute cerebellar degeneration
What is leukodystrophy?
aka Dysmyelinating diseases
Associated with mutations affecting the proteins required for formation of normal myelin or in mutations affecting the synthesis or degradation of myelin lipids
Most common demyelinating disorder
Multiple sclerosis
Multiple sclerosis is associated with this haplotype.
HLA-DR2
MS represents which type of hypersensitivity reaction
Type IV
The most common leukodystrophy is ___. It is characterized by a deficiency in ___
Metachromatic leukodystrophy.
Arylsulfatase A deficiency
Microcephaly occurs in chromosome abnormalities, fetal alcohol syndrome, and this infection acquired in utero.
Human immunodeficiency virus 1
In paretic neurosyphilis, there is parenchymal damage of the brain particularly in the ____ lobe.
Frontal.
Patient presents with progressive loss of mental and physical functions, with mood alterations. Histologically, loss of neurons seen along with rod cells (microglia)
Meningovascular neurosyphilis, like TB meningitis, is chronic, involves the brain base and may be associated with obliterative endarteritis. What is unique to meningovascular neurosyphilis?
Perivascular inflammatory reaction rich in plasma cells and lymphocytes
Histologic features of viral encephalitis
- Mononuclear cell infiltrate
- Microglial nodules
- Neuronophagia
Korssakoff syndrome is characterized by memory disturbances due to lesions in the ___.
Medial dorsal nucleus of the thalamus
Pattern of brain injury in hypoglycemia is similar to that seen in global hypoxia. How would you differentiate the two?
Purkinje cells of the cerebellum are relatively spared in hypoglycemia.
Carbon monoxide is toxic to the brain because it causes hypoxia. It also selectively injures this part of the brain.
Globus pallidus
Chronic alcohol exposure is associated with this morphologic change in the brain
Atrophy of the anterior vermis of the cerebellum causing cerebellar dysfunction
How does accumulation AB or B amyloid in Alzheimer lead to cell death?
- Aggregates can form plaques that are toxic to neurons and synaptic endings.
- AB hyperphosphorylate the tau protein which binds microtubules. When phorphorylated, tau redistributes into dendrites and cell bodies and aggregates into tangles.
Plaques, tangles and neuronal loss in Alzheimer’s are earliest seen in this region.
Entorhinal cortex
- > hippocampal formation and isocortex
- > neocortex
Bundles of paired helical filaments visible as basophilic fibrillary structures in the cytoplasm of neurons that displace or encircle the nucleus
NF tangles
This toxin is used in animal models of Parkinsonism.
MPTP
The lesion in Parkinson is in the ___ while the lesion of Huntington DIsease is in ___.
Parkinson: substantia nigra
Huntington: striatum
In Huntington disease, repeat (CAG) extensions occur during ___.
Spermatogenesis.
Paternal transmission is associated with early onset in next generation.
CAG (which is expanded in Huntington) codes for:
Glutamine
Polyglutamine tracts characteristically produced in Huntington
Normal alleles contain ___ copies of the CAG repeat that is expanded in Huntington.
11 - 34
Juvenile Huntington Disease develops when the repeat lengths exceed ___ copies.
70
Friedreich ataxia is characterized by expansion of this trinucleotide ___. What is the effect of the expansion on the protein product?
GAA
Mutation leads to low levels of protein involved in determining iron levels in cells.
Most common neurodegenerative disorder affecting the motor system
Lou Gehrig’s disease
Explain why Lou Gehrig’s Disease is more appropriately called Amyotrophic Lateral Sclerosis.
In this disease, there is loss of BOTH UMN and LMN.
Amyotrophic = muscle atrophy (LMN)
Lateral sclerosis = degeneration of the corticospinal tracts in the lateral cord (UMN)
Malignant peripheral nerve sheath tumor may arise from this precursor tumor.
NOT schwannoma!
Usually arise de novo or from transformation of a PLEXIFORM NEUROFIBROMA
What is the glioma that usually occurs in Type 2 neurofibromatosis
Ependymomas of the spinal cord
Characteristics of tuberous sclerosis
Cortical tubers and subependymal harmartomas (> seizures). Renal angiomyolipoma Retinal glial hamartoma Cardiac rhabdomyoma Hepatic, renal and pancreatic cysts Shagreen patches Ash-leaf patches Subungual fibromas
