Pathology for Midterm Flashcards by Stephen Barna

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

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*********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

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*********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

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*********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

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******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

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*******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)

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******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

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********* 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

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*******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

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*************____ 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

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********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

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***********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)

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**********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

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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

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*********Lesions involving the ___ vertebrae can lead to paraplegia and lesions to the ___ vertebrae can lead to quadriplegia

Thoracic, Cervical

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************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

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*************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

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*******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

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********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

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******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

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******____ 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

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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

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_____ 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

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*********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

Hyalinized

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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)

******Most MS patients are ___ in age, ___ in ethnicity, and their gender is ____ If they come in with an ____ problem (such as ____lateral vision impairment due to the optic nerve Morphologically, the lesions are firmer than the surrounding white matter (aka sclerosis) and appear ___ (well or poor?) circumscribed, depressed, glassy, ___-____ in color, and irregularly shaped plaques The CSF will have ___ protein levels due to inflammation, ____ is increased leading to ____ bands which is consistent with B cell activation (Anti-Myelin Abs even though this is mainly a T cell process, Oligoclonal bands are still characteristic) So once again, Olioglonal IgG bands represent active ___ cells and occur in the Gamma region ***************^^^^ THIS SHIT WILL BE ON THE TEST OR QUIZ

Young, Caucasian, Female Eye, Unilateral Well, gray-tan Increased, IgG, Oligoclonal B

Another demyelination syndrome is ____, which presents as a synchronous bilateral optic neuritis and spinal cord demyelination and is even more common in women than MS and involves ____

NMO (Neuromyelitis Optica), Anti-aquaporin 4 Abs

There are also some acute demyelination syndromes in which the damage occurs all at once (aka monophasic) compared to MS where the damage occurs over time and therefore multiple clinical episodes are seen Examples include ___ which is a diffuse, monophasic demyelinating disease generally follows a viral infection or anti-viral immunization OR ____ which is similar to ADEM (monophasic, etc...) but is more severe and has small blood vessel damage, disseminated necrosis of white and gray matter with acute hemorrhage, fibrin deposition, and abundant neutrophils preceded by a URI

ADEM (Acute disseminated encephalomyelitis) ANHE (Acute necrotizing hemorrhagic encephalomyelitits)

Degenerative diseases are those with progressive loss of neurons and associated secondary changes in white matter tracts First we start with the most common cause of dementia in older adults, ____ This affects the ____ of the brain (Diffuse, bilateral, cerebral cortical atrophy) ^***** so remeber AD is assocaited with diffuse, bilateal cerebrocorotical atrophy Morphologically, the accumulation of ____ plaques and ___ tangles cause this disease, but realize that the generation of the ___ is the CRITICAL initiating event for AD to develop ^** In other words, Tau deposits alone is not enough to cause AB deposition The combination of the ____ secretase cleavage product and ___ secretase cleavage product allows AB monomers to form -> AB oligomers -> Aggregates -> Fibrils -> Plaques **APP (Amyloid precursor protein), APOE (promotes AB generation and deposition), PS1 and PS2 (Presenilins 1 and 2 cause a gain of function leading to increased gamma-secretase complexes causing more AB complexes to be formed) are the genetic factors involved

Alzheimers Cerebral cortices AB, Tau, AB Beta, Gamma

As we already discussed, Alzheimers disease is ALWAYS considered as Diffuse, Bilateral, Cerebral Cortical Atrophy in terms of the disease distribution Patients present with progressive disorientation, memory loss, loss of learned motor skills and aphasia, and a cortical dysfunction Like we also already said, neuritic plaques and neurofibrillary tangle are present, along with ____ degeneration, ___ bodies, neuronal loss, CAA, and reactive gliosis Also realize most of these cases are sporadic

Granulovacuolar, Hirano

____s are diseases that regionally affect the cerebral cortices aka focal degeneration of the frontal and/or temporal lobes ^* aka they are NOT diffuse cerebral cortical diseases like Alzheimers *******OFTEN THIS IS VERY HARD TO TELL BETWEEN FTLD AND AD, HOWEVER, they can be distinguished from AD because following memory loss there is alterations in personality, behavior, and language (Aphasia)... Also if you see imaging with more degeneration in the frontal and temporal*********************** ^ KNOW THIS Like AD, there is also dementia 1) One form of FTLD is FTLD-____, which has been called Picks disease due to the fact that the Tau neuronal depositions are called Pick bodies ^** Here, the affected cortical regions have progressive neuronal loss, reactive gliosis, and tau-containing inclusion bodies in the cytoplasm of neurons ********(Unlike AD, there is NO AB accumulations)***** So if you see Tau inclusions with severe atrophy restricted to a specific lobe, think Pick disease with FTLD-tau accumulations 2) FTLD-TDP-43 is another type of FTLD with localized cortical atrophy (aka it has the same cortical distribution as FTLD-tau, but instead of tau neuronal inclusions, there are TDP-43 neuronal inclusions which is an RNA binding protein) 3) FTLD-FUS is also an RNA-binding protein is the other type of FTLD And can be associated with both FTLD and ALS

FTLD (Frontotemporal dementias) 1) FTLD-Tau

____ (Amyotrophic lateral sclerosis) also called Lou Gehrig's disease is the prototypical motor neuron disease "Motor neuron diseases" are a separate category compared to "movement" diseases and defined as neurological syndromes in which either an excess or movement or a paucity of a voluntary and automatic movements, unrelated to weakness or spasticity So once again, don't confuse "motor neuron diseases" with "movement" disorders associated with the degeneration of the ___ and ___ Movement disorders are divided into 2 major categories including 1) ____ movements aka dyskinesias which are repetitive, involuntary movements that intrude into the normal flow of motor activity The best example of a hyperkinetic disorder is ___ 2) ____ movements which refer to akinesia (aka lack of movement), hypokinesia (reduced amplitude of movements), bradykinesia (slow movements), and rigidity The best example of a hypokinetic disorder is ___

ALS Basal ganglia and brain stem (extrapyramidal diseases?) 1) Hyperkinetic Huntingtons 2) Hypokinetic Parkinsons

Tremor, Rigidity, and Bradykinesia would bring one to consider ____ disease ^** Other clinical features include diminished facial expression, stooped posture, slowing voluntary movements, festinating gait, rigidity, and tremor Parkinson like syndromes are associated with the depletion of ____ pathways in the basal ganglia (specifically, the ____) that are needed to modulate feedback from the thalamus to the motor cortex PD is associated with protein accumulation and aggregation, mitochondrial abnormalities, and neuronal loss in the substantia nigra ^************The substantia nigra and locus ceruleus will have a pallor appearance due the catecholaminergic neuronal loss (like we just talked about above with dopamine being one example of a catecholamine) and one will also see ___ bodies found in remnant neurons composed of aggregates of ___************************* Along with Alpha-synuclein (an autosomal dominant genetic mutation), 2 other genetic associations of differing protein accumulations include ____ (an AD inheritance) and ____ dysfunctions (autosomal recessive) such as DJ-1/PINK1/parkin

Parkinson Dopaminergic nigrostriatal , substantia nigra Lewy, Alpha-Synuclein LRRK2, Mitochondrial

There are also other degenerative diseases of the basal ganglia and brainstem that are not Parkinson's diseases and therefore NOT responsive to L-DOPA, however they have similar clinical features These diseases include: 1) Dementia with Lewy bodies 2) ____ which shows Tau inclusions in neurons and glial cells instead of the alpha-synuclein normally seen in Parkinson's and patients develop truncal rigidity, disequilibrium with frequent falls and difficulty with voluntary ____ movements 3) CBD (Corticobasilar degeneration) 4) ____ affects different systems and are characterized by cytoplasmic inclusions of Alpha-Synuclein in ____ (NOT neurons like in Parkinson's)**** aka in glail cells associated with the degeneration of white matter tracts

2) PSP (Progressive supranuclear palsy), eye | 4) MSA (Multiple System Atrophy), oligodendrocytes

Huntington's disease is the prototypical hyperkinetic movement disorder with autosomal dominant inheritance *********One characteristic is involvement of the ___ of the basal ganglia***************** This disease occurs due to a mutated gene called huntingtin (HTT), which expresses a toxic ___ of function mutation causing increased CAG repeats ^** Normal is 10-26 repeats and affected have 36-121 repeats *******Clinical features include ____ (aka irregular) movements and dementia such as irregular, SPASMODIC, and hypotonic of limbs/head/neck This also last for 15-20 years and early on they are slow, writhing involuntary movements (athetotic movements) and later progress to dementia, fecal and urinary incontinenece, etc

Caudate nucleus Gain Choreiform

Spinocerebellar degenerations (aka spinocerebellar ataxias) are similar to Huntington's disease and can be divided into 3 categories including 1) If a patient has symptoms similar to Huntington's disease and dies from cardiomyopathy, it is most likely _____******************** ^** The mutated gene product is called ____ 2) If a patient has a recurrent sinopulmanry infection (most commonly caused by ____ fungus), then often ____ can occur with its mutated gene product being ____ ^** Patients with Ataxia telangiectasia have enlarged cells in many organs referred to as ____

1) Friedreich Ataxia Frataxin 2) Mucor, Ataxia telangiectasia, ATM protein Amphicytes

Motor neuron diseases can refer to 5 different diseases, although ALS is the most common one when someone specifically says "motor neuron disease" In order to differentiate them, we can base it off the concept of which motor neurons (UMN, LMN or both) are affected State if UMN, LMN, or both are affected for the motor neuron diseases 1) ALS 2) PLS (Primary lateral sclerosis) 3) PMA (Progressive muscular atrophy) 4) PBP (Progressive bulbar palsy) 5) Pseudobulbar palsy ** ALS is a degenerative disorder of the pyramidal motor system

1) Both 2) UMN 3) LMN 4) LMN (bulbar region) 5) UMN (bulbar region)

There is NO sporadic ____ disease, it is all familia However, there IS sporadic ALS aka not typically genetic Patients with ALS have generalized muscle weakness and atrophy and early signs of asymmetric weakness of the hands are seen as patients tend to drop things and have difficulty performing fine motor tasks ALS might be due to ____ or ____ mutations

Huntington SOD1 or C9orf72

One common mitochondrial encephalopathy disease (disorders of energy generation) is ___ syndrome which is a diseases of infancy characterized by lactic acidemia, hypotonia, seizures, arrest of psychomotor development, and more ____ is another that presents with myoclonic epilepsy and ___ red fibers

Leigh Syndrome MERRF, Ragged

Acute mental confusion, ataxia, and ophthalmoplegia is a triad seen in ____ due to a deficiency in ___ This can be treated with B1, however, if left untreated it will turn into an irreversible syndrome called ____ syndrome where short term memory and confabulations also occur Wernickes is characterized by foci of hemorrhage and necrosis in the ____ and walls of the ____ ** Both can be associated with chronic alcoholics Also chronic alcoholics will have histological changes such as atrophy and loss of granule cells mainly in the ____

Wernicke encephalopathy, Vitamin B1 (Thiamine) Korsakoff Mammillary bodies, 3rd and 4th ventricles Anterior Vermis

The vast majority of malignancies in adults are in the ____ In kids, they are mainly in the ____ Aka supratentorial for adults and infratentotial for children

Cerebral cortices Posterior fossa

The most common types of primary brain tumors are _____ and include astrocytomas, along with oligodendrogliomas and ependymomas Astrocytomas can be either infiltrating or localized Of the infiltrating astrocytomas, they are graded based on the clinical course and outcome including ____ (2/4), ____ (3/4), or _____ (4/4) (the worst outcome) Glioblastomas vary in their appearance from region to region and have central necrosis and vascular/endothelial cell proliferation along with _____ histological features Glioblastomas can be further divided into primary vs secondary and the most common primary subtype is ___ (PTEN or EGFR defects) and the most common secondary is ____ (***____ defects***)

Gliomas Diffuse, Anaplastic, Glioblastoma Pseudo-palisading Classic, Proneural, IDH1

If one sees a cystic mass, with a mural nodule and in a CHILD, then the most common tumor is a ____ Also ____ fibers and eosinophilic granule bodies are characteristic findings Pilocytic astrocytomas are associated with ___ and ___ mutations ^** Cerebellar hemangioblastomas present similar Unlike diffuse astrocytomas, these pilocytic astrocytomas ___ (do or do not?) have infiltration of the surrounding brain

Pilocytic astrocytoma Rosenthal TP53 and BRAF Do NOT

Oligodendrogliomas are infiltrating gliomas comprised of cells that resemble oligodendrocytes These are well circumscribed, gelatinous, gray masses often with cysts, focal hemorrhage, and 90% of these have coarse ____ that can be seen even on plain films ********* To tell the difference between oligodendrogliomas and astrocytic tumors one can look at the molecular defects and in oligos, there is alterations in the ___ genes or deletions on chromosome ____ and ____ ^** Those with deletions on the chromosome respond well to chemotherapy and those without those deletions do NOT If an adult has their first seizure with no seizure history, this could be a problem

Calcifications IDH1 and IDH2 (Isocitrate dehydrogenase), 1p and 19q

Ependymoma often occur near the ____ and often associated with defects in the ___ gene on chromosome 22 Often histologically, perivascular _____ are seen A distinct but related lesion called ___ ependymomas occur around the cauda equina and filum terminale of the spinal cord

4th ventricle, NF2 Pseudorosettes Myxopapillary

So if there is an adult with a single lesion in the cerebral cortices they most likely have a ____ If there is a single lesion in the posterior fossa of a child (in midline) it is probably a ____ *********A meduloblastoma ONLY resides in the ____ Multiple lesions are normally metastatic tumors **** So to clarify, if there is a question that tells you there is a single lesion in the posterior fossa of a child, specifically, the cerebellum, you 100% think _____ and if the question says there is a cystic lesion in the posterior fossa of a child, does not tell you specifically where (although it could be in the cerebellum), and also says that rosenthal fibers are present, you think _____

Glioma Meduloblastoma Cerebellum (aka posterior fossa aka infratentorial) Meduloblastoma, Pilocytic astrocytoma

Younger adults that present with seizures might have a neuronal tumor (which are less common than glial tumors) Examples include 1) Gangliogliomas which present in the ____ lobe, and can be cystic.

Temporal

Medulloblastomas are a CNS primitive neuroectodermal tumor (PNET) (aka one of the small ___ cell tumors) ^** They tend to occur around the 4th ventricle in children and only in the cerebellum Rapid growth can occlude CSF flow leading to hydrocephalus and often the tumor is well circumscribed, gray, and friable with sheets of anaplastic cells and ____ and ____ markers Sometimes the tumors disseminate through the CSF causing nodular masses at sites distant from the primary tumor aka "drop metastases" ___ is a highly aggressive skeletal muscle differentiation tumor that occurs in the very young and defects in chromosome 22 are seen in 90% of cases

Blue Ki-67 and GFAP AT/RT (Atypic teratoid/rhabdoid tumor)

Primary CNS lymphomas are composed of ___ cells with the marker CD___, multifocal and the term "primary" means it arose in the brain ^**Also common in immunosuppressed (HIV) patients ___ is seen as the characteristic feature in primary CNS lymphomas ____ cell tumors are common in Male Japanese patients near the pineal gland

B cell, CD20 Hooping Germ

Meningiomas are ___ (benign or malignant?) tumors, usually attached to the ____ ____ bodies are seen in these tumors************ and like oligodendrogliomas if there are enough you can see them on plain films (since they are calcifications) ^** Most meningiomas are 1/4 but ____ meningiomas are 2/4 and include Clear cells and Chordoid; ____ meningiomas are 3/4 and include Papillary and Rhabdoid meningiomas ** Also prior radiation therapy to the head and neck, typically decades earlier, is a risk factor for development

Benign, dura Psammoma Atypical, anaplastic

Metastatic tumors can arise in patients and intraparenchymal metastases form sharpply demarcated masses often at the junction of gray and white matter, surrounded by a zone of edema Patients with diverse metastatic tumors can develop paraneoplastic syndromes that involve the PNS or CNS and include: ____ is characterized by the development of hamartomas and benign neoplasms involving the brain and other tissues ^** In the CNS, hamartomas take the form of ____ Cysts and hemangioblastomas (found in the retina or cerebellum) are seen in ___ disease ^** Hemangioblastomas are highly vascularized neoplasms that occur as a mural nodule associated with a large-fluid filled cyst which makes their presentation extremely similar to pilocytic astrocytomas, so to tell the difference realize that if the question was asking for PA, it would tell you rosenthal fibers were seen and if asking for a cystic hemangioblastoma, you will likely see cysts in other organs like the liver etc

Tuberous Sclerosis complex Brain tubers Von Hippel-Lindau disease

Peripheral nerve sheath tumors include Schwannomas, Neurofibromas, and MPNSTs Neurofibromas are seen in NF1 and NF2, with the most common being NF___ ^** 3 types of NFs, superficial cutaneous, diffuse (where Pseudo___s are seen), and plexiform NFs that have a "bag of worm" appearance Schwannomas, meningiomas, and ependymomas are found in NF type ____ Schwannomas are encapsulated, benign tumors that result from a loss of ___ and NEVER become malignant... They are characterized by ___ A and B and __ bodies are also seen Patients with ____ Neurofibormas often end up with MPNST (Malignant peripheral nerve sheath tumors) and in these tumors one will see divergent differentiation called ___ tumors

1 Pseudo-meissner corpuscles 2 Merlin, Antoni, Verocay Plexiform, Triton

The most common malignancy of the eyelid is ____ ^** Lower eyelid and medial canthus are most common sites One will see a depressed central area and superficial ____, also you would want to excise the lesion quickly _____ also affects the eyelid, but this is seen as a local mass that diffusely thickens the eyelid and has a much higher potential for metastasizing compared to BCCs, which are very invasive LOCALLY So if you see a tumor of the eyelid that has metastasized, think ____ and if you see a tumor of the eyelid that has locally invaded, think ____

Basal cell carcinoma Telangiectasia Sebaceous carcinoma SC, BCC

Osteogenesis imperfecta might be diagnosed when a patient's ____ is blue in color ^** Surgical incisions into the sclera heal bad

Sclera

The anterior chambers is bound anteriorly by the cornea, laterally by the ____, and posteriorly by the iris ____s are lenticular opacities that can be congenital or acquired The lens fibers do not have the intracellular mechanisms to deal with the accumulation of substances and the lens does not shed the nonviable cells, leading to a cloudy lens that scatters light and is the leading cause of blindness in the world

Trabecular meshwork Cataracts

African americans and hispanics are much higher risk for ____ Also, age (over 60), diabetics, and prolonged corticosteroid use are risk factors Commonly associated with increased ____ and has characteristic ___ nerve and visual field changes aka ____ of the optic never There is angled open and angle closed glaucomas Angle ____ has the aqueous humor with complete physical access to the trabecular meshwork causing the increased Intraocular pressure to result from the increased resistance to aqueous outflow in the open angle ^** In other words, the the aqueous humor is able to go from the posterior chamber to the anterior chamber, but then the T-meshwork is blocked leading to increased ICP from outflow blockage Open angle glaucomas have been associated with MYOC and OPTN gene mutations Angle ____ has the peripheral zone of the iris adhere to the trabecular meshwork leading to physical impeding the egress of aqueous humor from leaving the eye ^** Increased psoterior chamber pressure leading to bowing of the iris and blockage of the meshwork via angle closure is ____ary and often found in those with hyperopia ***** If asked on a test, it will be PRIMARY ANGLE-CLOSURED rather than secondary

Glaucoma Intraocular pressure Optic, cupping Open Closed Primary

The most common intraocular malignancy of adults is metastasis to the ____, which is made up of the iris, choroid, and ciliary bodies ^** Usually, the ______ gets the most metastases Uveal ___ are the most common primary intraocular malignancy of adults ^** Uveal melanomas are not the same as uveal ____s, which are benign (rarely transform to melanomas) melanocytic lesions that also are located in the posterior uvea, commonly as choroidal nevis Uvea melanomas occur due to defects in ____ and ____; and uveal nevis also have these defects, with the addition of ____ deletions on chromosome 3 Uveal melanomas (not nevis) will have ___ and ___ cells, along with the presence of _____ slit-like spaces lined by laminin that surround packets of tumor cells Finally, these melanomas spread through the blood (hematogenous) to the ___

Uvea Choroid Melanomas Nevis GNAQ and GNA 11, BAP1 Spindle and Epithelioid, Looping Liver

The most common primary intraocular malignancy in children is ____ The patient will present will small, round cells with hyperchormatic nuclei and if well differentiated, ____s can be seen It is due to a defect in the RB Focal zones of _____ are CHARACTERISTIC for RBs

Retinoblastomas Flexner-Wintersteiner rosettes Dystrophic calcification

The inability to read and poor vision at night, along with choroidal neo-vascularization is associated with _____ ^** Occurs between the RPE and Bruch membrane (BM) If there is the presence of neoangiogenesis , it is the ___ form and if there is no neoangiogenesis it is the ___ form Dry ADM can not be cured, but wet ADM is treated via injecting ____ into the vitreous of the affected eye Also, ADM is commonly associated with the genetic defects in ____

Wet Macular degeneration (ADM) Wet, Dry VEGF antagonists CFH

The end-stage eye is called _____

Phthisis bulbi

Thinning of the cornea with breaks in the Bowman layer are hallmarks for _____, causing the cornea to have conical rather than spherical shapes leading to an irregular form of astigmatism

Keratoconus

The most common primary neoplasms of the orbit are vascular in origin and include ______ which occur in infancy/childhood and are un-encapsulated Lymphangiomas are also un-encapsulated In adults, the encapsulated ___ is common ** Only a small number of orbital masses are encapsulated including ____ of the lacrimal gland, dermoid cysts, and neurilemomas

Capillary hemangioma Encapsulated cavernous hemangioma Pleomoprhic adenomas

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Although Huntington's disease is characterized by spasticity and choreiform movements, if one sees spasticity and choreiathetoid movements is a very young child it would be due to ____ (a NON-progressive condition)

Cerebral palsy

Ischemic encephalopathy, diffuse cerebral edema, and communicating hydrocephalus all affect both sides of the brain, however if there is a question that talks about only a single cortex being affected, then you would want to think about a ____ in one of the cerebral cortexes leading to significant edema which can cause headache, blurry vision in one eye, and problems with gaze, and dilation ^******* THIS WILL BE ON THE TEST Patient will have no previous history, seizure manifestations, unilateral eye problems with vision and dilation, and headache = _____

Glial tumor (like an astrocytoma) Astrocytoma

Once again, a IDH1 and GFAP + single mass lesion is most likely a ____

Glioblastoma

A ring-enhancing cerebro-cortical mass associated with increased WBCs, increased eosinophils, and emphysema with focal calcified nodules and scattered cavitary lesion, you should think a ___ brain abscess

Fungal

If you see an elderly patient with confusion, a headache, and CT scan of bilateral hemorrhage in the superio-lateral aspects of the cerebral hemispheres, you would consider a ___ hematoma due to the fact that it is associated with mild trauma

Subdural

If you see a patient with atypical megakaryocytes, think ____

Alzheimers disease

If you see a MCV (Macrocytic anemia) think ____ deficiency leading to subacute combined degeneration of the spinal cord

Vitamin B12

If you see a patient with dementia, slappy gait, b/l joint pain, hydrocephalus, fibrosis of the meninges, perivascular accumulations and lymphoplasmacytic cells, think _____ ^** Plasma cells sometimes called gumma cells ^** Remember, NS is usually caused by _____

Neurosyphilis T- Pallidum

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Cerebral palsy

Glial tumor (like an astrocytoma) Astrocytoma

Once again, a IDH1 and GFAP + single mass lesion is most likely a ____

Glioblastoma

Fungal

Subdural

If you see a patient with atypical megakaryocytes, think ____

Alzheimers disease

If you see a MCV (Macrocytic anemia) think ____ deficiency leading to subacute combined degeneration of the spinal cord

Vitamin B12

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Cerebral palsy

Glial tumor (like an astrocytoma) Astrocytoma

Once again, a IDH1 and GFAP + single mass lesion is most likely a ____

Glioblastoma

Fungal