Pathology for Midterm Flashcards
Acute neuronal injury occurs from acute CNS hypoxia or ischemia resulting in early onset of neuronal cell death
^** 12-24 hours after the injury occurs, ____ neurons are seen with features of a shrunken cell body, pyknosis (chromatin condensation) of the nucleus, loss of nucleolus, and loss of Nissl substance with intense eosinophilia of the cytoplasm
Subacute and Chronic neuronal injury result from a progressive disease of some duration with the characteristic feature being cell ___ and reactive ___ (aka glial scar formation)
Red
Cell loss, gliosis
*********The axonal reaction is a change observed in the cell body during regeneration of the axon, best seen in the anterior horn cells of the spinal cord when motor axons are cut or seriously damaged
Axonal ____ are often seen in various pathological conditions such as POST-TRAUMATIC DIFFUSE AXONAL injury or in older individuals in the dorsal medulla oblongata
There is increased protein synthesis associated with axonal sprouting and this leads to enlargement and rounding up of the cell body aka Axonal spheroids, along with peripheral displacement of the nucleus, enlargement of the nucleolus, and dispersion of Nissl substance from the center to the periphery
Spheroids
*********Cerebral cortical (aka the cerebral cortex) atrophy aka a decrease in the size of the brain tissue, generally causes the ____ to expand since the brain is attempting to compensate in order to fill the cranial vault
^** The reason atrophy occurs after trauma is due to the fact that the neurons are reabsorbed and this is seen as atrophy
Ventricles
*********The BBB in the CNS contains
1) Capillaries lined by continuous ____ cells linked by ____ junctions
2) The basal lamina
3) Perivascular ____ end feet
Astrocytes have a MAJOR ROLE in CNS wound healing** and instead of ending up with a scar, you end up with a ____ structure/lesion
1) Enothelial, tight
3) Astrocytic
Cavitary
******Reactions to astrocyte (reactive astrocytosis) injury include ____, which is extremely important in indicating CNS injury and is characterized by hypertrophy AND hyperplasia of the astrocytes, along with accumulation of ____ (Glial fibrillary acidic protein aka a type of intermediate filament)
_____ fibers are thick, elongated, brightly eosinophilic irregular structures that occur within astrocytic processes and contain 2 HSPs and ubiquitin (dense bundles of glail filaments)
^** They represent condensation from previous glial damage (aka found in regions of long standing gliosis) and are cahracteristic of pilocytic astrocytomas
So once again, CHRONIC reactive fibrillary astrogliosis will be accompanied by rosenthal fibers
____ aka polyglucogan bodies aka “brain sand” are round, basophilic, periodic acid-schiff (PAS) positive located wherever there are astrocytic end processes, especially in the subpial and perivascular zones and are seen in arachnoid granulation
Cellular swelling is also seen
___ is when there is bubbly vaculoization of the neuropil (visible cytoplasm)
Gliosis, GFAP
Rosenthal
Corpora amylacea
Gemistocytic
*******Increased fluid leakage from the blood vessels or injury to various cells of the CNS is due to ____ and can lead to increased ICP (due to edema, increased CSF, or expanding mass lesions)
** In generalized edema, the gyri are ___, sulci are ___, and ventricular cavities are compressed
There are two ways this can occur
1) ____ edema (most common) is when there is an increase in extracellular fluid due to the ***____ being disrupted and with increased vascular permeability, the fluid is able to leave the vessels (intravascular compartments) and move into the spaces in the brain (intercellular spaces)
^** IVC -> Intercellular (aka interstitial) spaces of the brain
2) ___ edema occurs due to a secondary defect in neuronal, glial, or endothelial cell membranes allowing the intracellular fluid to be increased aka fluid can leak into the cells (intRAcellular)
^** So for an example of cytotoxic edema, a patient could have an ischemic/hypoxic injury causing defect in astrocytes leading to problems of maintenance of the normal membrane ionic gradient and fluid now escapes from the intravascular compartments
*** Generalized edema usually contains elements of both, leading to flattened gyri, narrowed intervening sulci, and compressed ventricular cavities
** So realize Vasogenic is intERcellular (aka intERstitial) aka the fluid is filled up between the cells in the interstitial space and cytotoxic is intRAcellular aka the cells themselves become filled with fluid
** ____ edema usually occurs due to a tumor or mass lesion whereas ____ edema usually occurs due to ischemia/hypoxia***
____ edema is when there is an increased in intravascular pressure that causes an abnormal flow of fluid from the intraventricular CSF across the ependymal lining to the periventricular white matter
Cerebral Edema
Flattened, narrowed
1) Vasogenic, BBB
2) Cytotoxic
Vasogenic, Cytotoxic
Interstitial (aka hydrocephalic)
******Excess accumulation of CSF within the ventricular system is called ____
If the ventricular system is obstructed and does not communicate with the subarachnoid space such as in the case of a mass in the 3rd ventricle, it is called a ____ hydrocephalus
^** In kids, the most commonly obstructed is the cerebral aqueduct connecting the 3rd and 4th ventricles and in non-communicating the ventricles are dilated ____
If the ventricular system is communicating with the subarachnoid space and the entire ventricular system is enlarged, it is called ____ hydrocephalus… One example is blockage at the arachnoid granulations which can be caused by ____ syndromes
^** Aka the CSF is not absorbed properly at the dural sinus level causing the ventricles to be ____ dilated
An increase in ventricular volume secondary to a loss of brain parenchyma (bilateral cerebral cortical atrophy) is called ____
Hydrocephalus
Non-communicating aka obstructive
Asymmetrically
Communicating, Chronic meningeal
Symmetrically
Hydrocephalus ex vacuo
********* Herniations can occur due to increased ICP and symptoms include Headache, ____ in the eyes, and others
Name the type of herniation
1) ____ herniation occurs when there is a unilateral or asymmetric expansion of the cerebral hemisphere causes displacement of the cingulate gyrus under the falx
^** This can cause compression of the ____ artery and its branches
********2) ____ herniation occurs when the medial aspect of the temporal lobe is compressed against the free margin of the tentorium
^** The ____ cranial nerve, ____ artery, and if big enough the contralateral cerebral ____ can all be compressed from this herniation
** Due to the transtentorial herniation, the cerebellar peduncles can be compressed against the tentorium cerebelli, which will lead to ____lateral hemiparesis or hemiplegia (aka loss of motor function) to the side of the herniation and this is called the ____**********
^** So if there is a mass lesion on the right side causing a treanstentiorial herniation, the left cerebral peduncle will be compressed and since that causes contralateral hemiparesis/hemiplegia it will therefore present on the right side (which is the same aka ipsilateral side of the herniation)
This type of herniation can also progress leading to secondary hemorrhagic lesions in the midbrain and pons called Duret hemorrhages
3) ____ herniation is when the cerebellar tonsils herniate through the foramen magnum and this can cause brainstem compression and death
If one sees Duret Hemorrhages (aka slit hemorrhages), it is characteristic of a ___ herniation
Papilledema
1) Subfalcine (aka cingulate) herniation
ACA (Anterior Cerebral artery)
2) Transtentorial (aka Uncinate aka Mesial temporal) herniation
3rd CN, PCA (Posterior Cerebral artery), Peduncle
**Ipsilateral, Kernohan notch ****
3) Tonsillar
Transtentorial
*******An overlying meningeal out-pouching with a patch of hair is ____
A meningeal extrusion with no CNS protrusion is ____
A meningeal extrusion WITH CNS protrusion is ____
Neural tube defects can often occur due to ____ deficiencies
Spina Bifida
Meningocele
Myelomeningocele
Folate
*************____ is a malformation characterized by reduction in the number of gyri and comes in 2 types
^** Don’t confuse with the flattened gyri seen in edema
Type 1 is due to mutations in the signaling for migration of the cytoskeletal motor proteins that drive neuroblast migration
Type 2 is due to genetic defects in the stop signal for the migration
Neuronal ____s are defined as the presence of collections of neurons in inappropriate locations along the pathway of migration and associated with ____
____ is when incomplete separation of the cerebral hemispheres across the midline occur and often associated with trisomy 13 and mutations of the Sonic HedgeHog signaling pathway
Lissencephaly
Heterotopias, Epilepsy
Holoprosencephaly
********POSTERIOR FOSSA ANOMALIES*
____ type 1 and 2 malformations are involved with the cerebellar tonsils extending down into the vertebral canal due to a ____ posterior fossa
^** KNOW THIS DEFINITION
^** Type 2 is more severe and involves a small posterior fossa, downward extension of the cerebellum’s vermis through the foramen magnum and most of the time also hydrocephalus and a lumbar myelomeningocele
____ can be associated with Chiari malformations which is a fluid filled cleft-like cavity within the inner portion of the spinal cord and is characterized by the isolated loss of ____ sensations in the ____ extremities
Dandy-walker malformations are due to a 1) ____ fossa vault causing the 2) cerebellar vermis to be absent and in its place is an expanded, roofless, fourth ventricle, and 3) dysplasia of the brainstem nuclei
^** I would be able to recognize these 3 symptoms**
BOTH CHIARI AND DANDY CAN LEAD TO HYDROCEPHALUS
Joubert syndrome involves hypoplasia of the cerebellar vermis and elongation of the superior cerebellar peduncles
Arnold-Chiari, small
Syringomyelia, pain and temp, upper
Enlarged
***********Non-progressive ** (so whatever defects child born with, they don’t progress) neurologic motor deficits characterized by spasticity, dystonia, ataxia/athetosis, and paresis is called _____ and these injuries occur during the prenatal and perinatal periods, but often don’t appear until birth
In premature infants, they are at an increased risk for ____ hemorrhage (aka bleeding within the brain parenchyma -> remember, parenchyma is the white and gray matter of the brain)
^** Premature infants are also at an increased risk for ____ which takes the form of chalky yellow plaques leading to white matter necrosis and calcification; and if both white AND gray matter are involved in an infract, large destructive cystic lesions throughout the hemispheres can develop called ____
** In perinatal ischemic lesions of the cerebrum, the depths of the sulci bear most of the injury leading to thin, gliotic gyri called ulegyria
Cerebral palsy
Intraparenchymal, Periventricular leukomalacia (PVL), Multicystic encephalopathy (MCE)
**********Symptoms related to the lower cranial nerves or the cervicomedullary region, along with orbital or mastoid hematoma distant from the site of impact suggest a ____
^** Fractures that cross suture lines are called diastatic fractures
The parenchyma can be injured from contusions (bruise from blunt trauma) or lacerations (penetrating injury)
____ on cross section are wedge shaped with a broad base lying along the surface at the point of impact. Morphological evidence of neuronal injury is seen 24 hours after characterized by pyknosis, eosinophilia, and disintegration of the cell
***** So in summary, parenchymal injuries take the form of contusions that leads to hemorrhage which can extend into the subarachnoid space
Old traumatic lesions present as depressed, yellow-brown, retracted patches involving the crest of the gyri and this is called plaque Jaune
Along with the surface of the brain being affected, Diffuse Axonal Injury can develop affecting the deep white matter regions with eventual increase in microglia and eventual degeneration of the involved fiber tracts aka the body can NOT repair and you end up with ___ formation… Because remember, SPHEROIDS = POST-TRAUMATIC DIFFUSE AXONAL INJURY
^** So sometimes after trauma occurs, even if no cerebral contusions are seen, there can be diffuse axonal injury leading to coma and death
Basal skull fracture
Contusions
Spheroid
Along with skull and parenchymal injuries, vascular injuries can occur after trauma
Blood pooling between the dura and the periosteum on the internal surface of the skull is called an ____ hematoma and this most commonly occurs from the ___ being severed
^** Commonly associated with trauma due to ____ and ___ evolving neurological signs and this IS AN EMERGENCY
Also realize that sometimes Lucid Intervals are associated with epidural hematoma (lose consciousness, wake up, then lose it again) but is NOT diagnostic
When blood pools between the inner surface of the dura (meningeal dura layer) and the arachnoid layer it is called a ___ hematoma and this is due to the ___s being severed (these veins dump into the superior sagittal sinus)
^** Commonly associated with trauma (can be only a MILD trauma) and ____ evolving neurological signs aka 48 hours
^** Acute subdural hematoma occur as collections of freshly clotted blood along the brain surface with NO extension into the sulci. The underlying brain is flattened and the subarachnoid space is clear. Usually the bleeding is self-limited and eventually it is broken down and organized over time
There is also ___ formation with a subdural hematoma
Months to years after a brain trauma, neurological problems might manifest (called sequelae of brain trauma) such as in posttraumatic ____ due to obstruction of CSF from hemorrhage into the subarachnoid space, or ____ which occurs from re-accuring brain injuries leading to atrophic, enlarged ventricles, with accumulated tau-containing neurofibrillary tangles in a superficial frontal and temporal lobe cortex pattern
So one more time, although not diagnostic, the LUCID INTERVAL is most commonly seen in ___ hematomas
Epidural, Middle meningeal artery (MMA)
^** Note this is NOT the MCA**
Skull fractures, Rapidly
Subdural, Bridging veins
Slow
Membrane
Hydrocephalus, CTE (Chronic traumatic encephalopathy)
Epidural
*********Lesions involving the ___ vertebrae can lead to paraplegia and lesions to the ___ vertebrae can lead to quadriplegia
Thoracic, Cervical
************Cerebrovascular disease (often called a ___) is when the brain becomes damaged from inadequate blood supply
^** So a STROKE is the clinical term for acute-onset neurologic deficits resulting from hemorrhagic or obstructive vascular lesions
- Note that TIA (Transient Ischemic Attack) is a stroke with NO neuro damage
It can be thought of as being due to 2 processes
1) Hypoxia/Ischemia/Infraction resulting in impaired blood and O2 supply to the CNS tissue
^** Often due to an ____ rather than a thrombus (Remember, embolism is when a clot travels through the blood vessels and settles down and a thrombus is when the clot forms and doesn’t move)
^** The most common cause of an embolism to the brain is from ____ with myocardial infracts, valvular disease, and atrial fibrillations as important predisposing factors
** Realize that hypoxia is a lack of O2 from low PO2, decreased bloods O2 carrying capacity, or decreased O2 use by the tissue… Whereas Ischemia is a decrease in the blood supply to the tissue aka interruption of the normal circulatory flow from hypotension (reduction in perfusion pressure) or vessel obstruction
2) Hemorrhage from the CNS vessels being ruptured due commonly due hypertension and vascular anomalies like aneurysms (a weakness in blood vessels in the brain that fill with blood and can pop) and malformations
A thrombotic stroke implies there normally NOT hemorrhage
Stroke
Embolism
Cardiac mural thrombi
*************When there is GENERALIZED reduction of cerebral perfusion such as in a cardiac arrest, shock, or severe hypotension, ____ cerebral ischemia aka diffuse ischemic/hypoxic encephalopathy can occur
^** It can be mild or severe
Global ischemia is caused by blood loss, and the ischemic event (no matter what it is throbotic, embolotic, etc…) affects BOTH cerebral cortices and the outcome is not good…
^**Prognosis is very poor, but if it is a transient global ischemia, the prognosis is not as bad
Other than global cerebral ischemia, Local ischemia also can occur and has a better prognosis than global
One example is ____ infracts that occur at regions of the brain or spinal cord that lie at the most distant reaches of the arterial blood supply (commonly between the border zone of the ACA and MCA)
^** Damage results in a sickle-shaped band of necrosis over the cerebral convexity a few centimeters lateral to the inter-hemispheric fissure
Often, a local stroke LATERALIZES*** So if the patient is going blind in one eye, or weakness on one side of the body, consider a local stroke!******
For global ischemia, the brain becomes edematous and swollen leading to widened gyri and narrowed sulci.
^** Early morphological changes (12 to 24 hours) consist of red neurons (diffuse eosinophilia of neurons) and eventually injury to astrocytes and oligodendrocytes.
^ After the acute injury, neutrophils begin to infiltrate where the vascular supply has remained intact and after 24 hours to 2 weeks (aka 10 days), tissue necrosis, macrophage infiltration, vascular proliferation, and reactive gliosis has occurred
Finally, after 2 weeks repair begins by removing necrotic tissue, CNS architecture changes, an gliosis leading to a pattern termed _____ necrosis
Global
Watershed
Pseudolaminar necrosis
*******Unlike global cerebral ischemia with GENERALIZED reduction of cerebral perfusion, ___ cerebral ischemia occurs when a LOCALIZED area of the brain loses blood flow due to arterial occlusions or hypoperfusions
When ischemia is sustained, an infract will occur
Remember, focal cerebral infracts are most commonly from ____s
Focal
Embolisms
********The territory of distribution of the ____ artery is the most commonly affected by embolic infracts (remember, this artery comes off the internal carotid artery)
Hemorrhagic lesions that involve white matter are characteristic of ____ embolizations after trauma
Also thrombotic occlusions associated with atherosclerosis and plaque rupture can cause cerebrovascular disease and inflammatory processes can as well including infectious vasculitis, polyarteritis nodosa, and primary angiitis of the CNS
*************If once has a unilateral occlusion of the MCA there will be ____lateral hemiplegia (paralysis) affecting the face, arm, and leg; ___ affecting the ipsilateral head and eye deviation is ____ the side of stroke; and if it occurs on the left a global ___ will occur (aka loss of language)
^** So as an example, a Left MCA embolism = Aphasia, Right Hemiplegia (similar to hemiparesis) and right sensory loss (face and arm mostly affected), left hemianopsia (aka left visual field cut) and gaze is TOWARDS the side of stroke aka gaze to the left
^** Mnemonic = CHANGe -> C = contralateral paresis and sensory loss in face and arm, H = Homonymous Hemianopsia, A = Aphasia, N = Neglect, G = Gaze towards size of lesion
MCA
Bone marrow
Contralateral, homonymous hemianopia, towards, aphasia
******Infracts are divided into 2 main groups based on if there is hemorrhage or not
1) ____ infracts occurs first when an infract leads to loss of blood supply
^** After 48 hours, the tissue becomes pale, soft, swollen, and the corticomedullary junction becomes indistinct. From 10 days to 3 weeks, the tissue liquifies and becomes a fluid filled cavity aka the nonhemorrhagic infract turns into a ____ lesion meaning that the dead tissue is removed rather than repaired
Microscopically, after the first 12 hours ischemic neuronal changes occur (aka red neurons) along with cytotoxic and vasogenic edema. Astrocytes swell and myelinated fibers disintegrate. Reactive astrocytes developing a network of cytoplasmic extensions can be seen 1 week after injury
^**48 hours in, the phagocytic cells and microglia predominate and do so for the next 2 to 3 weeks. Finally after several months, the astrocytic response decreases leaving behind a meshwork of glial fibers mixed with new capillaries and some perivascular connective tissue
2) Hemorrhagic infracts occurs due to ischemia-____ injury with the hemorrhages being ____ in nature
^** The evolution is similar to non-hemorrhagic infracts except for the addition of blood extravasation and resorption
1) Non-hemorrhagic
Cavitary
2) Reperfusion, petechial
******____ can also cause cerebrovascular disease leading to slit hemorrhages, hypertensive encephalopathy, and lacunar infracts
Hypertension is the risk factor most commonly associated with deep brain parenchymal hemorrhages
1) ___ infracts can occur when hypertension affects the deep penetrating arteries and arterioles that supply the basal ganglia and hemispheric white matter along with the brainstem causing the cerebral vessels to become occluded due to arteriolar sclerosis (build up of fats, cholesterols, and other substances in the artery walls)
^** Lentculostriate arteries (which come off the MCA) are the major site for these
2) ____ hemorrhages are when hypertension causes rupturing of small-caliber penetrating vessels leading to slitlike cavities surrounded by brownish discoloration
3) Acute hypertensive encephalopathy occurs in the setting of ____ hypertension (aka extremely high hypertension that occurs very rapidly) characterized by diffuse cerebral dysfunction like headaches, confusion, vomiting, and convulsions
^** The brain becomes edematous and petechiae and fibrinoid necrosis of the arterioles in the gray and white matter can be seen microscopically along with CB microaneurysms, and multi-infract dementia (aka vascular dementia)
^** If a patient has multiple infracts (aka vascular dementia) and the pattern of injury affects mainly areas of subcortical white matter with myelin and axon loss, it is called ___ disease
Hypertension
1) Lacunar
2) Slit
3) Malignant
Binswanger
Unlike bleeding in the epidural or subdural space commonly from trauma, bleeding inside the parenchyma (intraparenchymal hemorrhage) often occurs from some form of cerebrovascular disease with the two most common causes being hypertension and cerebral amyloid angiopathy
^** So once again, the most common risk factor associated with deep brain parenchymal hemorrhages are ____ due to the fact that it causes vessel wall weakening exposing them to rupture easier
*** Most commonly, these hypertensive intraparenchymal hemorrhages originate in the putamen, thalamus, pons, cerebral hemispheres, etc.
^ Acute hemorrhages are characterized by the extravasation (leakage) of blood with compression of the adjacent parenchyma And older hemorrhages have a rim of brownish discoloration
Chronic hypertension can lead to minute aneurysms called Charcot-Bouchard microaneurysms most commonly in the basal ganglia
Hypertension
_____ is most commonly associated with lobar hemorrhages (frontal lobe, parietal lobe, etc…) and is caused by amyloid deposits in the walls of vessels, causing them to become weak
^** A feature of chronic inflamation
Often, micro-bleeds (many small hemorrhages) are seen and a polymorphism in the gene ____ with an E2 or E4 allele will increase ones risk with CAA for repeat bleeding
Another hereditary small vessel disease is CADASIL (Cerebral autosomal dominant arteriopathy with subcortical infracts and leukoencephalopathy) is caused by mutations in ___ leading to the characteristic presence of basophilic, PAS-positive deposits containing misfolded NOTCH3 protein
CAA (Cerebral amyloid angiopathy)
ApoE
NOTCH3
*********The most frequent cause of a clinically significant sub-arachnoid hemorrhage aka bleeding into the subarachnoid space, is the rupture of a ____ in a cerebral artery
So if you see a patient with ONLY clinical finding being a subarachnoid hemorrhage, think -> Ruptured aneurysm Of the circle of willis***
Most saccular aneurysms are found near arterial branch points in the _____ (anterior or posterior?) circulation - usually along the circle of Willis (aka by the ACA, or by ICA, etc)
These aneurysms have NO smooth muscle and intimal elastic lamina and instead the sac is made up of thickened ___ intima and a covering of adventitia
They most commonly occur in the firth decade of life (50 yr) and more common in women. They can occur at anytime but most commonly when an increased intracranial pressure occurs such as with straining at stool or a sexual orgasm
^** Patients will present with a HORRIBLE headache and then lose consciousness
Hours to days after this occurs, increased risk of additional ischemic injury from vasospasm affecting the vessels bathed in blood and once the injury begins to heal, meningeal fibrosis/scarring can result in CSF obstruction and decreased CSF absorption
Saccular (aka Berry) aneurysm
Anterior
Hyalinized
Another cause of a spontaneous subarachnoid hemorrhage can come from vascular malformations, which are classified into 4 categories
1) ____ involved vessels in the subarachnoid space, brain, or both and consists of pulsatile AV shunting (Artery -> Vein) with high blood flow AKA blood passes quickly from the artery to veins and bypasses the normal capillary network
^** AVM is most common at the site of the MCA’s posterior branches and occurs 2x as often in males aged 10-30
2) ____ consist of distended, loosely organized vascular channels arranged back to back with collagenized walls of variable thickness and the blood flows very slowly
^** They also tend to leak since the vessels don’t have the proper support and junctions and there is usually NO brain parenchyma between the vessels
3) Capillary telangiectasias are small foci of dilated, thin-walled, vascular channels separated by NORMAL brain parenchyma and occur most commonly in the ___
1) AVM (Arteriovenous malformations)
2) Cavernous malformations
3) Pons
******____ is inflammation of the leptomeninges (composed of pia and arachnoid matter that forms the subarachnoid space) and CSF within the subarachnoid space, usually due to infection
____ is the inflammation of the meninges and brain parenchyma
Infectious meningitis is classified into
1) Acute pyogenic (usually ____ infections)
2) Acute/subacute Aseptic (usually ___ infections)
3) Chronic
Meningitis
Meningoencephalitis
1) Bacterial
2) Viral
********1) Acute pyogenic (bacterial) meningitis
A) ____ and ____ cause it in infants (birth-3 months)
B) ____ in young adults
C) ____ and ____ in older adults
Neurological impairment like headache, neck stiffness, etc… Is seen and a spinal tap shows a cloudy CSF (aka leptomeningeal opacity/exudate) with increased ____ infiltration into the subarachnoid space (since remember, this is a bacterial infection), ____ protein content, and ____ glucose
*********^^^^ KNOW THIS SHIT FOR ALL TYPES OF MENINGITIS
Leptomeningeal fibrosis can follow pyogenic meningitis and cause hydrocephalus (commonly a communicating hydrocephalus) and in pneumococcal (step pneumoniae) meningitis, large quantities of the capsular polysaccharide of the organism produces gelatinous exudates that promote arachnoid fibrosis called ____
^** So in other words, CAA is a term used for the thickening fibrosis phenomena that might occur in the leptomeninges
_____ syndrome results from meningitis-associated septicemia (bacteria in the blood due to meningitis) with hemorrhagic infraction of the adrenal glands and cutaneous petechiae
A) E Coli and Group B strep
B) Neisseria Meningitidis
C) Strep Pneumoniae and Listeria Monocytogenes
Neutrophil, Increased, Decreased
Chronic adhesive arachnoiditis (CAA)
Waterhouse Freiderichesen syndrome
******2) Acute/Subacute aseptic (viral) meningitis occurs when no bacterial organisms are cultured and most commonly it is due to ____ virus
Unlike Pyogenic, the CSF is ____ in color compared to the cloudy CSF found in bacterial infections, there is an increased ____ count rather than neutrophils, protein elevation is not as highly elevated as in pyogenic, and ____ glucose content
Enterovirus
Clear, Lymphocyte (aka lymphocytic pleocytosis), normal
*******Acute focal suppurative infections such as brain _____ are localized areas (focus) of necrosis of the brain tissue accompanied by inflammation, usually from a bacterial infection most commonly ____ or ____
Abscesses are discrete lesions with central liquefactive necrosis surrounded by brain swelling
^** Brain edema is due to the outer margins of the necrotic lesion having exuberant granulation tissue with neovascularization around the necrosis
Patients present with focal neurological deficits, high WBCs in the CSF, increased protein, and normal glucose
Another localized infection is an subdural ___ which is an infection of the skull bones or air sinus that spreads to the subdural space and can produce a mass effect of thrombophlebitis of the bridging veins leading to venous occlusion and infraction of the brain
^** This is normally a poly-microbial infection such as staph and anaerobic gram - bacteria
Abscess, Streptococci and Staphylococci
Empyema
******Chronic bacterial meningitis or meningoencephalitis (both brain and meninges) most commonly occurs from ____ but caN also come from Neurosyphilis, Treponema Pallidum or Neuroborrelia aka lyme disease, or Cryptococcus
^** The most common pattern of a M. Tuberculosis infection is ____ meningoencephalitis causing the subarachnoid space to contain a gelatinous or fibrinous exudate that involves the ___ of the brain
Microscopic examination shows mixed inflammatory infiltrates, increased protein levels, and sightly reduced glucose
The most serious complication is arachnoid fibrosis leading to hydrocephalus or obliterative endarteritis producing arterial occlusion and infracts
Remember, M Tuberculosis can be seen via ____ staining methods and CNS involvement might occur from intraparenchymal masses called ____ that have a central area of ____ necrosis surrounded by a granuloma
Mycobacterium tuberculosis
Diffuse, Base
Acid-fast, Tuberculomas, caseous
The manifestation of the tertiary phase of syphilis is referred to as ____ and presents in 3 distinct forms, often patients have a combination of the forms
1) ____ neurosyphilis is chronic meningitis that involves the base of the brain and often the cerebral convexities and spinal leptomeninges
^** Distinct perivascular inflammatory reaction rich in plasma cells and lymphocytes and cerebral gummas (plasma cell rich mass lesions) may also occur
2) ___ is when T. Pallidum invades the brain and characterized by ____ alterations leading to severe dementia (general paresis of the insane)
^** Parenchymal in the cerebral cortex’s frontal lobe is common, with loss of neurons, microglia proliferation, gliosis, and iron deposits seen via the ____ stain
3) ___ is when the sensory axons in the dorsal roots are damaged leading to loss of pain and proprioception below the level of the lesion, loss of DTR, destruction of the dorsal columns of the spinal cord, and lightning pains
Neurosyphilis
1) Meningovascular
2) Paretic, mood
Prussian blue
3) Tabes dorsalis
*********Viral ____ is a parenchymal infection of the brain, most commonly associated with inflammation of the meninges (meningoencephalitis) or spinal cord (encephalomyelitis)
^** There is NO bacterial encephalitis
Arthropod-born encephalitis (arboviruses) are important cause of epidemic encephalitis, especially in ___ regions of the world
^** The different arboviruses have similar changes but differ in extent and severity. The changes include meningoencephalitis marked by perivascular accumulation of ____ (and sometimes neutrophils), multiple foci of necrosis of gray and white matter, specifically called ____ (single-cell neuronal necrosis with phagocytosis of the debris), small aggregates of microglial cells around foci of necrosis is called ____
** So just recognize these are findings for viral morphology
Encephalitis
Tropical
Lymphocytes, Neuronophagia, microglial nodules
******Encephalitic syndromes include
1) ___ occurs most commonly in kids and young adults and involves the inferior and medial regions of the TEMPORAL lobes and the orbital (cingulate) gyri of the FRONTAL lobes
^** KNOW HSV-1 = Temporal and Orbital Gyri of Frontal
The infection is necrotizing and hemorrhagic and perivascular infiltrates along with Cowdry type A intranuclear viral inclusion bodies are present in neurons and glia
Unlike HSV-2, HSV-1 is associated with ___ lesions
2) HSV-2 is acquired in neonates passing through the birth canal of infected parents
Often associated with ___ lesions
3) Herpes zoster can be reactivated in adults (shingles) and usually self-limited, but in patients over 60 it can lead to postherpetic neuralgia syndrome and cause granulomatous arteritis
4) CMV affects fetuses and immunosuppressed patients and if infected in utero, periventricular necrosis will cause brain destruction
^**Associated with periventricular _____ and common in HIV patients
^** In immunosuppressed patients with CMV, it usually causes ____ associated with CMV inclusion-bearing cells and the infection localizes in the paraventricular ____ regions of the brain leading to sever hemorrhagic necrotizing ventriculoencephalitis and a choroid plexitis. There will also be prominent enlarged cells with intranuclear and intracytoplasmic inclusions
5) Acute cases of poliomyelitis show mononuclear cell perivascular cuffs and neuronophagia of the ____ motor neurons of the spinal cord
KNOW Polio = Anterior Horn
^** Clinical features include meningeal irritation and CSF similar to that of aseptic meningitis. If disease affects the motor neurons, it will lead to flaccid paralysis, muscle wasting, and hyporeflexia
6) ____ causes severe viral encephalitis and ****ALWYAS one will find ____, which are cytoplasmic, round-oval, eosinophilic inclusions found in the pyramidal neurons of the hippocampus and Purkinje cells of the cerebellum
^** Non-specific neurological symptoms but local parasethesias around the bite site is a more specific indication
1) HSV-1
Oral
Genital
4) Calcifications
Subacute encephalitis, subependymal
5) ANTERIOR HORN
6) Rabies, Negri bodies
KNOW SLIDE 79 in Path Lecute 2!!!!!!!!
Bacterial vs Viral vs Fungal/TB
1) For a bacterial infection, the type if inflammation is ____, Cell type is ____, glucose is ____, protein levels are ____
2) For a viral infection, the type if inflammation is ____, Cell type is ____, glucose is ____, protein levels are ____
3) For a fungal infection, the type if inflammation is ____, Cell type is ____, glucose is ____, protein levels are ____
1) Purulent, PMN, Decreased a lot, increased
2) Lymphocytic, Mononuclear, Normal, Normal/slightly elevated
3) Lymphocytic, Mononuclear, Decreased slightly
HIV encephalitis is a chronic inflammatory reaction where one will see ____ nodules and multi-nucleated ___ cells
^** Remember, microglial nodules are not specific for HIV, just that it is a viral infection
^** Depending on how many ____ cells (the inflammatory cell of the CNS) are activated, will determine the amount of HIV dementia in the patient aka Dementia is associated with chronic inflammation
If one sees a ___ CNS ____, it is almost always associated with HIV
___ also occurs only in HIV patients and is a viral encephalitis caused by ____ that infects _____, leading to lots of myelin loss in the CNS (aka demyelination)
**Clinical signs include progressive neurological symptoms with extensive, multifocal lesions in the white matter due to the breakdown of oligodendrocytes
Microglial, Giant
microglial
Primary CNS lymphoma
PML (Progressive multifocal leukoencephalopathy), JC polyomavirus, oligodendrocytes
Fungal meningoencephalitis also usually occur in immunocompromised patients and commonly causes
1) ____ meningitis
2) Vasculitis via invading the blood vessel walls (usually due to ___ or ____)
3) Parenchymal invasion (from ___ or ____)
4) ____ fungi can cause the parenchymal invasions to lead to multiple micro-abscesses
^** In a cryptococcal infection, the subarachnoid space will show small cysts within the parenchyma called _____
_____ is known to complicated asthma
1) Chronic
2) Mucor or Aspergillus
3) Candida or Cryptococcus
4) Candida
Soap bubbles
Asprigillis
Protozoa include Cerebral ____ that causes abscesses in the cerebral cortex near the gray-white junction and deep grey nuclei
^** So congenital toxoplasmosis can present as multiple calcifications (aka abscesses) in the brain
Cerebral malaria due to ____ is a rapidly progressive encephalitis due to vascular dysfunction leading to decreased cerebral blood flow causing ataxia, seizures, and coma
So once again, micro-abscesses with parenchymal invasion think ____ or abscesses in the cerebral cortex think ____
Toxoplasmosis
Plasmodium falciparum
Candida (a fungus), Toxoplasma gondii (a protozoa)
Prion diseases are abnormal forms of a cellular protein (called PrP) that cause rapidly progressive neurodegenerative disorders that can be sporadic familial, of transmitted
They are all characterized by ____ changes caused by intracellular vacuoles in neurons and glia leading to a rapidly progressing dementia
It occurs when PrP___ changes to PrP___ and acquires resistance to protease digestion
The three important prion diseases include
1) _____ progresses clinically as a rapidly progressing dementia marked by subtle changes in memory and behavior first then rapid dementia associated with startle myoclonus (involuntary jerking muscle contractions on sudden stimulation)
2) ____ is characterized pathologically by the presence of extensive cortical plaques surrounded by a halo of spongiform changes and is linked to Bovine Spongiform Encephalopathy
^** Similar to CJD, but occurs in ____ and neurological symptoms progress slower
In both CJD and vCJD, ____ are extracellular deposits of aggregated abnormal tissue seen in the ____ for CJD and ____ for vCJD
3) _____ is characterized by sleep disturbances in the initial phases
^** The best way to diagnosis this type of prion disease is to have a + test for Protein K-resistant PrPsc and see NO ___ changes**
Spongiform
PrPc -> PrPsc
1) CJD (Creuzfeldt-Jakob disease)
2) vCJD (Variant CJD)
Young adults
Kuru Plaques, cerebellum, cerebral cortex
3) Fatal familial Insomnia
Spongiform
____ diseases are those with damage to myelin, but sparing of axons.. The clinical defects are due to damaged electrical conduction along axons
The prototypical disorder of demyelination, and most chronic neurological disease of young people is ____
There are relapsing and remitting episodes of variable duration marked by neurological deficits
The MS plaques are predominantly in white matter that occur as multiple, well-circumscribed, depressed, glassy, ___-____ in color, irregularly-shaped plaques
It is an immune response directed against components of the MYELIN SHEATH and involve both genetic and environmental factors
MS is due to ____ cells (aka cell mediated immunity) that react against the myelin antigens (aka an autoimmune resposne) and secrete cytokines (Th1 secretes IFN-gamma to activate macrophages) and recruit inflammatory cells (via Th17) and the activated leukocytes and their injurious products cause demyelination
Demyelinating
Multiple Sclerosis (MS)
Gray-tan
T cells (CD4+ TH1 and TH17)
