Chapter 28: The CNS - Intro Flashcards
Which cell type is evident 12-24 hrs after acute CNS hypoxic/ischemic insult?
Red neurons (“red dead guys”)
Morphology of red neurons
- Shrinkage of cell body
- Pyknosis of nucleus
- Dissapearance of nucleolus
- Loss of nissl substance
- Intense eosinophilia of the cytoplasm
What are the hallmarks of subacute and chronic neuronal injury (i.e., degeneration)?
- Cell loss —> Apoptosis
- Reactive gliosis
What is gliosis?
Proliferation of astrocytes in response to brain injury
What is the axonal reaction?
Best seen where?
- Change observed in cell body during regeneration of the axon
- Best seen in anterior horn cells of SC when motor axons cut
Most important histopathologic indicator of CNS injury regardless of etiology?
Characterized by what 2 things; what cell?
- Gliosis
- BOTH hypertrophy and hyperplasia of astrocytes
Morphology of the axonal reaction?
- Enlargement and rounding up of cell body
- Peripheral displacement of nucleus
- Enlargement of nucleolus
- Dispersion of Nissl substance from the center to the periphery of the cell (central chromatolysis)
Which cells of the CNS are most sensitive to insult?
- Pyramidal neurons (hippocampus)
- Neocortical Betz cells
- Cerebella purkinje cells
Intracellular inclusions seen in herpes, rabies and cytomegalovirus?
Where specifically in the cell is each seen?
- Cowdry body (intranuclear): herpes
- Negri body (intracytoplasmic): rabies
- Both nucleus and cytoplasm: CMV
Intracytoplasmic inclusions seen in Alzheimer’s and Parkinson disease?
- Neurofibrillary tangles: Alzheimer’s disease
- Lewy bodies: Parkinson’s disease
Abnormal vacuolization of the perikaryon and neuronal cell processes in the neuropil are seen in what disease?
Creutzfeldt-Jakob
__________ act as the metabolic buffers and detoxify the brain; also contributing to the BBB (foot processes)
Astrocytes
What is the intermediate filament found in Astrocytes and can be stained for?
GFAP
Gliomas are positive for which stain?
GFAP
What are characteristics of a gemistocytic astrocyte?
- Nucleus enlarges, become vesicular, and develop prominent nucleoli
- Bright pink cytoplasm, forms swaths around the eccentric nucleus that forms numerous stout ramifying processes
Characteristics of Alzherimer Type 2 Astrocyte?
- Gray matter cell
- Large nucleus (2-3x)
- Pale-staining central chromatin
- Intranuclear glycogen droplet
What type of astrocyte is seen in pt’s with long-standing hyperammonemia due to chronic liver disease (will have flapping tremor of hands with extension of the wrist, asterixis), Wilson disease, or hereditary metabolic disorders of the urea cycle?
Alzheimer Type II Astrocyte
What type of cytoplasmic inclusion bodies are characteristic of Pilocytic Astrocytoma and also found in regions of long standing gliosis?
Rosenthal fibers
Which heat-shock proteins are found in Rosenthal Fibers?
- αB-crystallin
- hsp-27
*Also ubiquitin
What is Alexander disease and what cellular changes are seen in this disease?
- Leukodystrophy due to mutation in GFAP
- Rosenthal fibers, but more commonly seen are corpora amylacea (aka polyglucosan bodies)
Corpora amylacea (aka polyglucosan bodies) are positive for which stain?
PAS positive
______ are mesoderm derived phagocytic cells that serve as resident macrophages of the CNS
Microglia
Which round, faintly basophilic, concentrically lamellated structures increase with age and are though to represent degenerative changes in the astrocyte?
Corpora amylacea (aka polyglucosan bodies)
What are the cell surface markers of Microglia?
CR3 and CD68
What are 4 ways microglia respond to injury?
1) Proliferation
2) Dev. elongated nuclei (rod cell), as in neurosyphillis
3) Microglial nodules: microglia aggregate around small foci of necrosis
4) Neuronophagia: microglia congregate around cell bodies of dying neurons
How does the myelination ability of oligodendrocytes differ from schwann cells?
- Oligodendrocytes myelinate numerous internodes on multiple axons
- Schwann cells in peripheral nerve, has a one-to-one correspondance between cells and internodes
Injury or apoptosis of __________ cells is a feature of acquired demyelinating diseases and leukodystrophies?
Oligodendroglial cells
Glial cytoplasmic inclusions, primarily composed of ______ are found in oligodendrocytes in multiple system atrophy (MSA).
α-synuclein
What are Ependymal cells and where are they found in the CNS?
Ciliated columnar epithelial cells lining the ventricles
Disruption of the ependymal lining and prolferation of subependymal astrocytes produces what on ventricular surfaces?
Ependymal granulation
Which agent may produce extensive ependymal injury, with viral inclusions in ependymal cells?
CMV
Do oligodendrocytes or ependymal cells mediate significant responses to most forms of injury in the CNS?
NO
What is the response of astrocytes to neuronal injury?
- Hypertrophy of the cytoplasm, accumulation of GFAP, and hyperplasia
What is the response of microglia to neuronal injury?
Proliferate and accumulate during CNS injury
What is Vasogenic edema and is often seen following what?
- Increased EXTRAcellular fluid due to BBB disruption and increased vascular permeability
- Fluid shifts from INTRAvascular compartments to INTERcellular spaces
- Can be either localized (i.e., adjacent to neoplasms or inflammation) or generalied often follows ischemic injury
What is Cytotoxic edema and when is it seen?
- Increase in INTRAcellular fluid secondary to neuronal, glial, or endothelial cell membrane injury
- Generalized hypoxic/ischemic insult or w/ metabolic derangment
In practice, will oftens see elements of which type of edema(s)?
What morphological characteristics of the brain will be seen and this can lead to?
- Both vasogenic and cytotoxic edema
- Gyri flattened, sulci narrowed, and ventricles compressed —> Herniation!
What type of injury is associated with localized vs. generalized vasogenic edema?
- Localized: adjacent to inflammation or neoplasms
- Generazlied: follow ischemic injury
What is the most common cause of noncommunicating (obstructive) hydrocephalus in the neonate/infant?
Aqueductal stenosis
Enlargement of the entire ventricular system (“symmetric dilation”) due to accumulation of CSF not being properly absorbed at the dural sinus level is known as?
Communicating (“non-obstructive”) hydrocephalus
What 2 congenital conditions cause ventricular system obstruction?
1) Acqueductal stenosis
2) Dandy-Walker malformation
What is Hydrocephalus Ex-Vacuo?
Whom is it seen in?
What is the CSF pressure?
- Compensatory increase in ventricular volume secondary to loss of brain parenchyma
- Atrophy with increasing age, stroke or other injury, chronic neurodegenerative disease
- CSF pressure is NORMAL!!!
Herniation is displacement of brain tissue due to _____ or ______
Mass effect or Increased intracranial pressure
What is diffuse vs. focal mass effect that is associated with herniation?
- Diffuse: generalzied brain edema
- Focal: tumors, abscesses, or hemorrhages
Subfalcine herniation involves displacement of the _______ under the _______
Cingulate gyrus under the falx cerebri
A subfalcine herniation may lead to compression of the ________ artery leading to infarction
Anterior Cerebral artery (ACA)
What symptoms would result from Subfalcine herniation with compression of the ACA?
Contralateral lower extremity weakness
Transtentorial (uncinate, mesial temporal) herniation occurs when?
Which specific part and of which lobe?
MEDIAL aspect of the TEMPORAL lobe is compressed against the free margin of the tentorium
What are 3 possible consequences of progression of transtentorial herniations?
1) Compression of CN III —> pupillary dilation; eye is “down and out” (ipsilateral to lesion)
2) Compression of PCA —> ischemia of primary visual cortex
3) Large herniation may compress contralateral cerebral peduncle —> hemiparesis ipsilateral to side of herniation = Kernohan notch = “false localizing sign”
What are Duret hemorrhages and are a result of what?
- Progression of transtentorial herniation producing secondary hemorrhagic lesions in the midbrain and pon
- “Flame-shaped” lesions
Why is it crucial to exam the eyes of a patient you expect to be suffering from increased intracranial pressure?
Look for papilledema
What are congenital causes of hydrocephalus?
- Intrauterine infections (TORCH)
- Agenesis/atresia/stenosis
- Arnold chiari malformations
- Dandy walker syndrome
- Cranial defects: Achondroplasia and Craniostenosis
Which rare type of brain tumor leads to increased CSF production, thus causing increased ICP and hydrocephalus?
Choroid Plexus Papilloma/Carcinoma
What is the most common parasitic nervous system disease in the world and can lead to hydrocephalus?
- Cysticercosis
- Taenia Solium (pork tapeworm)
What are the characteristic of normal pressure hydrocephalus and who is it seen in?
- Symmetric type usually occuring in adults >60
- Develops slowly over time; drainage of CSF is blocked gradually
- Enlarged ventricles still exert pressure on brain and can become symptomatic w/ pt’s exhibiting dementia-like manifestatons
- Dementia may be similar to Alzheimers and gait abnormalities may suggest Parkinson disease
- NPH is often misdiagnoses as one of these diseases
What is the classic triad of clinical findings exhibited by patients with normal pressure hydrocephalus?
- “Wet, wacky, and wobbly”
- Often exhibit a magnetic gait
- Dementia-like sx’s; impaired recognition (often not severe)
- Urinary incontinence; appears late in illness and is generally of the spastic hyperreflexic, increased-urgency type
A right hemisphere trans-tentorial herniation, causes a Kernohan’s notch in the _____ cerebellar peduncle, which results in ________ motor impairment.
A right hemisphere trans-tentorial herniation, causes a Kernohan’s notch in the left cerebellar peduncle, which results in right-sided motor impairment.
What is a tonsillar herniation and why is it life threatening?
- Displacement of the cerebellar tonsils through the foramen magnum
- Can can brainstem compression and compromises vital respiratory and cardiac centers in the medulla
_______ refers to a diverticulum of disorganized brain tissue extending through a defect in cranium; most often occurring in the posterior fossa
Encephalocele (sometimes misleadingly referred to as a “nasal glioma”)
Malformation of the anterior end of the neural tube leading to a “frog-like” apperance of a fetus is known as?
Anencephaly
The migration of neurons from the germinal matrix zone to the cerebral cortex follows what 2 paths?
1) Radial migration for excitatory neurons; due to reelin protein signaling
2) Tangential migration for inhibitory neurons
The cause of Microcephaly is linked to?
- Chromosomal abnormalities
- Fetal alcohol syndrome
- HIV-1 acquired in utero
What is Lissencephaly and the 2 general patterns observed?
- Reduction in the # of gyri; sometimes agyria = NO gyri
- Type 1: smooth surfaced; mutations disrupting signaling for migration and the cytoskeletal “motor” proteins that drive migration of neuroblasts
- Type 2: rough or cobblestoned; disruption of the “stop signal” for migration of neuroblasts
Periventricular heterotopias can be caused by mutations in the gene encoding?
Filamin A, an actin-binding protein
Which forebrain anomaly is characterized by small, unusually numerous, irregularly formed cerebral convolutions?
Polymicrogyria
What are Neural heterotopias; commonly associated with?
- Group of migrational diseases that are commonly associated with epilepsy
- Defined by presence of neurons in inappropriate locations along pathway of migration
The microtubule-associated protein DCX is encoded by a gene on the X chromosome and mutations in this gene lead to what in males vs. females?
- Males: lissencephaly
- Females: subcortical band heterotopias
What is Holoprosencephaly? Severe forms produce which abnormalities?
- Incomplete separation of the cerebral hemispheres across the midline
- Cyclopia; less severe variants (arrhinencephaly) show absence of olfactory CNs
Holoprosencephaly is associated with what disease and signaling mutation?
- Trisomy 13
- Sonic hedgehog signaling pathway
Radiologic imaging showing a “bat wing” deformity is associated with that condition?
Agenesis of the corpus callosum
What is an Arnold-Chiari Type II malformation and what other abnormalities is it associated with?
- Small posterior fossa, misshapen midline cerebellum w/ downward extension of vermis through foramen magnum
- May also see caudal displacement of the medulla, malformation of tectum, acqueductal stenosis, hydromelia, and cerebreal heterotopias
- More severe than type I
- Associated with hydrocephalus and lumbar myelomeningocele
What is an Arnold-Chiari Type I malformation?
- Low-flying cerebellar tonsils extend down vertebral canal
- May be silent or become symptomatic due to impaired CSF flow and medullary compression
Which condition is associated with an enlarged posterior fossa, absence of cerebellar vermis w/ replacement by a large midline cyst representing an expanded roofless 4th ventricle?
Dandy-Walker Malformation
Which condition has hypoplasia of the cerebellar vermis, elongation of the cerebellar peduncle and an altered shape of brainstem; together giving a ‘molar tooth sign’ on imaging?
Joubert syndrome
Syringomyelia is associated with what other condition; how does it present?
What part of the spinal cord is involved?
- Associated w/ Arnold-Chiari Malformations
- Sensory loss of pain and temperature w/ sparing of fine touch and position in the UE’s (“cape-like” distribution) due to involvemet of the anterior white commissure of the spinothalamic tract
Expansion of the ependyma-lined central canal of the spinal cord is known as ________.
Hydromyelia
Dandy-Walker malformations have a large midline cyst that is lined by ______ and is continguos with _________ on its outer surface
Lined by ependyma and is contingous with leptomeninges on its outer surface
What is Cerebral Palsy and what are the clinical manifestations of this disease?
Occurs due to insults during which period?
- Non-progressive neurologic motor deficits characterized by combination of spasticity, dystonia, ataxia/athetosis, and paresis
- Pre-natal and perinatal periods (are present from birth)