Neuropath Monthly Exam

neuron

principal functional unit of CNS

Rosenthal fibers

eosinophilic collections of GFAP in astrocytic processes

abundant in pilocytic astrocytoma

subfalcine herniation

brain herniation characterized by unilateral/asymmetric expansion of cerebral hemisphere that displaces the cingulate gyrus under the falx

risk of anterior cerebral artery occlusion/compression

transtentorial herniation

brain herniation characterized by medial aspect of temporal lobe (uncus) becoming compressed against free margin of tentorium

risk of compression of CN III (fixed and dilated pupils), posterior cerebral artery (ischemic injury to visual cortex), midbrain (contralateral compression of cerebral peduncle leading to ipsilateral hemiparesis), brainstem (LOC)

tonsillar herniation

brain herniation characterized by displacement of cerebellar tonsils through foramen magnum

usually fatal due to compression of medulla leading to cardiorespiratory arrest

duret hemorrhages

secondary hemorrhagic lesions in midbrain and pons associated with the progression of transtentorial (uncinate) herniation

choroid plexus

produces cerebrospinal fluid

hydrocephalus

accumulation of excessive CSF within the ventricular system of the brain

can be due to obstruction, loss of cerebral tissue (ex vacuo) or overproduction of CSF (choroid plexus papilloma)

presents as headache, behavioral changes, lethargy and delayed development

non-communicating hydrocephalus

obstruction leads to dilation of ventricles upstream of CSF flow

causes include mass lesions, aqueductal stenosis, congenital malformations, tumors, some infections

communicating hydrocephalus

accumulation of CSF secondary to defective absorption or excess production

affects all ventricles

hydrocephalus ex vacuo

compensatory increase in ventricular volume secondary to loss of brain parenchyma

anencephaly

malformation of anterior end of neural tube with absence of brain and calvarium

agenesis of corpus callosum

absence of white matter bundles carrying cortical prohections from one hemisphere to the other

can be asymptomatic (anterior commissure can take over via plasticity)

Arnold-Chiari malformation

characterized by a small posterior fossa, a misshapen midline cerebellum with downward extension of vermis through the foramen magnum

causes hydrocephalus and a lumbar meningomyelocele

Type I Arnold-Chiari malformation

characterized by low lying cerebellar tonsils

downward herniation of tonsils with dilation of lateral ventricles from CSF obstruction

Type II Arnold-Chiari malformation

characterized by downward displacement of cerebellar tonsils and medulla through foramen magnum

tonsillar and brainstem herniation

Dandy-Walker malformation

malformation consisting of enlarged posterior fossa, absent or rudimentary cerebellar vermis and a large midline cyst

Periventricular leukomalacia

infarction occurring in supratentorial periventricular white matter, especially in premature babies

diastatic skull fracture

skull fracture that crosses sutures of the skull

coup injury

an injury to the brain occurring on the same side as the site of impact

contrecoup injury

damage to the brain surface diametrically opposite a blow to the head

cerebrovascular disease

injury to brain as a consequence of altered blood flow

grouped into ischemic and hemorrhagic etiologies

cerebral thrombotic occlusions

most commonly resulting from atherosclerosis and plaque rupture

cardiac mural thormbis

most common source of embolism to the brain

Watershed infarct

wedge-shaped areas of infarction occurring in regions of the brain and spinal cord that lie at the most distal fields of arterial blood supply

usually seen after hypotensive episodes

also called border zone infarcts

hypertension

most common underlying cause of deep brain parenchymal hemorrhage

saccular (berry) aneurysm

most common type of intracranial aneurysm

ruptured saccular (berry) anrurysm

most frequent cause of clinically significant subarachnoid hemorrhage

principle routes of CNS infections

hematogenous spread

direct implantation

local extension

ascending (peripheral nervous system)

neonatal acute pyogenic meningitis

most commonly associated with E. coli and Group B streptococci

infant/childhood acute pyogenic meningitis

most commonly associated with Haemophilus influenzae

adolescent/young adult acute pyogenic meningitis

most commonly associated with Neisseria meningitidis

elderly acute pyogenic meningitis

most commonly associated with Streptococcus pneumoniae and listeria monocytogenes

acute pyogenic meningitis spinal tap

shows an increased protein concentration and markedly reduced glucose content

brain abscess

predisposing factors include acute bacterial endocarditis, congenital heart disease, chronic pulmonary sepsis, systemic disease with immunosuppression

Negri body

pathognomonic microscopic finding in cases of rabies

JC polyomavirus

encephalitis characterized by progressive multifocal leukoencephalopathy

picornavirus

group of enteroviruses, including poliovirus, that can attack the anterior horn motor neurons of the spinal cord

injury from fungal infection of CNS

chronic meningitis

vasculitis

parenchymal invasion

prion disease

Creutzfeldt-Jakob disease

Gerstmann-Straussler-Scheinker syndrome

Fatal familial insomnia

Kuru

gliomas

astrocytoma

oligodendroglioma

ependymoma

pilocytic astrocytoma

most common localized astrocytoma typically occurring in children and young adults

glioblastoma

grade IV/V infiltrating astrocytoma

medulloblastoma

most common poorly differentiated (embryonal) CNS tumor

arising from the cerebellum and dorsal midbrain

WHO grade 4 - morphologically and genetically defined

primary CNS lymphoma

most common CNS neoplasm in immunosuppressed individuals

most often arise from B-cells

meningioma

tumors attached to the dura that arise from meningothelial cells of arachnoid mater

many morphologic variants

patients with neurofibromatosis type 2 can have multiple

50% of sporadic cases have loss of function mutations of NF2

psammoma bodies

structures in meningiomas that give the characteristic firm and fibrous to finely gritty texture

cafe au lait spots

cutaneous hyperpigmented macules in neurofibromatosis

Lisch nodules

pigmented nodules found in the iris of patients with neurofibromatosis type I

Von Hippel-Lindau disease

autosomal dominant disease marked by development of hemangioblastomas of the CNS and cysts of the pancreas, liver and kidney

Schwannoma

peripheral nerve sheath tumor

growth patterns include Antoni A and Antoni B

S100 immunoreactivity

Neurofibromatosis type I

systemic disease associated with non-neoplastic manifestations and tumors including neurofibromas, malignant peripheral nerve sheath tumors, optic nerve gliomas, glial tumors and hamartomatous lesions

holoprosencephaly

incomplete separation of cerebral hemispheres across the midline

presents as one hemisphere with a single ventricle

lissencephaly (agyria)

decrease in number of gyri to total absence

leaving a smooth surfaced brain

ependymal cells

ciliated columnar epithelial cells lining the ventricles of the brain

neurofibrillary tangles

tau-containing bundles of filaments in cytoplasm of neurons that can displace or encircle the nucleus

hallmark feature of Alzheimer disease

Parkinson disease

hallmark features include pallor of substantia nigra and Lewy bodies

protein aggregation

pathologic process most common across neurodegenerative diseases

multiple sclerosis

most common demyelinating disease

autoimmune demyelination disorder characterized by distinct episodes of neurologic deficits due to white matter lesions

unique features of the nervous system

localization of function - focal lesions produce specific deficits depending on anatomic location

unique cell lines - diseases are unique

key anatomic/physiologic features of the CNS

skull and spinal canal - provide rigid barrier

CSF - provides cushion against shock

blood-brain barrier - regulates transport of fluids, ions, macromolecules between vascular spaces

NO LYMPHATICS - immunologically privileged but prone to edema

neuronal reaction to injury

chromatolysis - injury at the cell body characterized by swelling, nuclear eccentricity, dispersal of Nissl substance to periphery of cell

Wallerian degeneration - occurs distal to point of injury with macrophages ingesting debris

acute hypoxic changes - shrunken, eosinophilic change with nuclear pyknosis, disappearing nucleolus

subacute/chronic change - cell loss and reactive gliosis

glial cells

astrocytes - support cells, stain with GFAP

oligodendrocytes - produce myelin (only in CNS)

ependymal cells - line the ventricles

microglia - derived from monocytes, transform into macrophages

astrocyte reaction to injury

gliosis - prominent nucleoli, bright pink-staining cytoplasm, also stains for GFAP

Rosenthal fibers - chronically reactive with lots of proteins, brightly eosinophilic

corpora amylacea - elaboration of astrocytic processes seen in normal aging

Alzheimer type II astrocytes

large, comma-shaped vacuolated nuclei

seen in hepatic encephalopathy as a reaction to circulating toxins from liver failure

not actually related to namesake disease

oligodendrocyte reaction to injury

limited response, but loss of myelin wraps

replaced by glial scars

ependymal cells

single layer of ciliated columnar cells that line the ventricles

injury response includes formation of 'granulations' usually in response to encepahlitis, meningitis

microglial response to injury

transform into macrophages

can form nodules - cluster around infected neurons

rod cells - proliferation response characterized by elongated nuclei

CNS inclusions

subcellular alterations of neuronal organelles and cytoskeleton structures that can be indicative of disease such as herpes simplex, CMV, Rabies (negri body), progressive multifocal leukoencephalopathy, and subacute sclerosing panencephalitis

cerebral edema

swelling of the brain due to breakdown of tight junctions between capillary endothelial cells of the blood-brain barrier

rigid skull provides little room for expansion + no lymphatics to drain excess fluid leading to increased intracranial pressure

morphology = boggy, heavy brain with flattened gyri, blurring of gray-white matter junction on cutting

vasogenic cerebral edema

involves direct damage to blood-brain barrier leading to increased capillary permeability and increased extracellular fluid

often seen in primary and metastatic tumors, abscesses

can respond to treatment with steroids

cytotoxic cerebral edema

damage to metabolism of neurons, glia leads to disrupted maintenance of fluid and electrolyte homeostasis and intracellular accumulation of fluid

most commonly associated with brain infarction

skull fractures

displaced - bone is displaced into cranial cavity by a distance thicker than the bone thickness

LOC prior to falling - frontal impact

orbital, mastoid hematoma - basal skull fracture

CSF leak from nose, ear - risk of infection, meningitis

diastatic fracture - crosses a suture line

concussion

clinical syndrome of altered consciousness secondary to head injury

usually due to change in momentum of head

onset of transient neurologic dysfunction due to dysregulation of reticular activating system in brainstem leading to LOC, temporary respiratory arrest, loss of reflexes

amnesia of event but neurological recovery

contusion

direct parenchymal injury caused by blunt trauma

tissue displacement, disruption of vessels and subsequent hemorrhage, edema

grossly appears as wedge-shaped with widest aspect at the point of impact

micro shows neuronal injury and hemorrhage

most commonly seen in crests of gyri in the frontal lobes, along orbital ridges and temporal lobe

plaque jaune

old contusion lesion

yellow, depressed area containing gliosis and hemosiderin-laden macrophages

risk of development into seizure focus

laceration

direct parenchymal injury characterized by penetrating object that tears through tissue

diffuse axonal injury

injury to the deep white matter or cerebral peduncles can lead to axonal swelling

epidural hematoma

collection of blood above the dura mater usually resulting from trauma with associated skull fracture

short period of consciousness followed by rapidly evolving neurological symptoms due to cerebral compression

middle meningeal artery is especially vulnerable to trauma

neurosurgical emergency

subdural hematoma

tearing of the bridging veins leads to bleeding between the layers of the dura

etiology often traumatic, but can be mild trauma with slowly evolving symptoms

brain atrophy increases risk

epidural and subdural hematoma

hematomas associated with trauma

subarachnoid hematoma

pooling of blood in the subarachnoid space (between pia mater and arachnoid membrane)

associated with rupture of saccular/Berry aneurysm, hypertension, AVM, trauma or coagulopathy

sudden onset of severe headache with rapid neurologic deterioration

encephalocele

a congenital herniation of brain tissue through a gap in the skull

spina bifida

a congenital defect that occurs during early pregnancy when the spinal canal fails to close completely around the spinal cord to protect it

failure of posterior vertebral arches to close leads to outpouching of disorganized segment of spinal cord covered by meninges

myelomeningocele

protrusion of the parenchyma and meninges of the brain or spinal cord through a defect in the cranium or vertebral column

meningocele

the congenital herniation of the meninges through a defect in the skull or spinal column

polymicrogyria

a condition associated with errors in cortical organization in which children have too many folds (gyri) in the cerebral hemispheres

megaloencephaly

abnormally large head and brain

microencephaly

abnormally small head

lissencephaly

The brain lacks sulci and gyri, and therefore appears smooth

Arnold-chiari malformation

developmental deformity of the hindbrain involving cerebellar tonsillar herniation

syringomelia

Cystic degeneration of the spinal cord

hydromelia

local dilation of central canal due to excess CSF

stroke

clinical designation for a vascular event in the nervous system

third most common cause of death in the US after heart disease and cancer

peaks between 60-70 years of age

M:F ratio of 1.5:1

brain area sensitivity to ischemia

hippocampus is most sensitive

cerebellar purkinje cells are second most sensitive

neurons of cerebral cortex are third most sensitive - can lead to laminar or pseudolaminar necrosis due to uneven destruction of neocortex

focal cerebral infarction

Occlusion within a specific vessel may lead to focal ischemia/infarction in territory supplied by that vessel

most commonly involved vessels include carotid bifurcation, middle cerebral artery, and basilar artery (either end)

lacunar infarct

small infarcts in brain due to occlusion of tiny blood vessels, especially the deep penetrating arteries/arterioles supplying the basal ganglia, hemispheric white matter and brainstem

usually occur in the setting of chronic, untreated hypertension

pt may also have concentric left ventricular hypertrophy

multi-infarct dementia

patients suffering from multiple, bilateral gray matter and white matter infarcts can develop distinctive clinical syndrome characterized by dementia, gait abnormalities, pseudobulbar signs with superimposed focal neurologic deficts

intracranial hemorrhage

results from damage to blood vessel wall

often related to hypertension

most commonly occurring in the basal ganglia, pons and cerebellum (same as sites of lacunar infarcts)

Charcot-Bouchard aneurysm

aneurysm at small artery bifurcations