Path Buzzin Flashcards
chromatolysis
seen in wallerian degeneration
red neurons
ireversible hypoxic injury - acute CNS injury
hepatic encephlaopathy
alzheimer type II astrocytes - they are damaged d/t high ammonia resulting in leakage and parenchymal edema –> cerebral edema
gliosis
GFAP + … think chronic CNS injury
test for CSF rhinorrhea
beta-2 transferrin
tumor in ventricle in kids?
lateral ventricle = choroid plexus papilloma- see papillary features
fourth ventricle = ependymoma - see rosettes
choroid plexus in adults is usually 4th ventrcile
SBS triad
encephalopathy, SD hematoma, retinal hemorrhages
- as well as severe brain atrophy and DAI
DAI
MVA or blow to unsupported head
- damages deep white matter –> wallerian degeneration
axonal swellings w/ beta amyloid protein build up
chronic traumatic encephalopathy
–> progressive depression and dementia d/t repetive DAI’s + concussions
build up of tau proteins, + tau stain - atrophy and loss of gray and white matter and dilated ventricles
subfalcine hernation
displaces cingulate gyrus under falx - may compress ACA
central herniation
CN VI –> lateral rectus palsy (inability to turn eye outward) and diplopia
bilateral uncal herniation –> paresis –> coma
uncal transtentorial herniation
herniation of medial temporal lobe through tentorium membrane
- impingement on corticospinal tract (cerebral peduncles) : hemiplegia, coma
o ipsilateral (kernohon’s) or contralateral d/t direct compression of uncus
o Compression of the cerebral peduncles → hemiplegia (paralysis of half of the body).
o often the hemiplegia is contralateral to the lesion either because of uncal herniation compressing the ipsilateral corticospinal tract in the midbrain, or because of a direct effect of the lesion on the ipsilateral motor cortex, or because of both.
o sometimes in uncal herniation, the midbrain is pushed all the way over until it is compressed by the opposite side of the tentorial notch (see Figure 5.6). In these cases the contralateral corticospinal tract is compressed, producing hemiplegia that is ipsilateral to the lesion. This is called Kernohan’s phenomenon. - CN III compromised → blown pupil
- may compress posterior cerebral artery, affecting primary visual cortex
tonisllar hernation
brain stem compromise –> resp and cardio effects –> death
duret hemorrhage
- herniation onto the brainstem compresses vessels and causes localized ischemia and bleeding into the pons and brainstem area
- caused by traumatic downward displacement of the brainstem, often secondary to raised ICP and formation of transtentoria pressure cone
- may be d/t uncal herniation
- results in ipsilateral hemiparesis to the lesion, often a false loclalizing sign
HIE
gray matter affected more than white
- see red neurons after reperfusion, interstitial edema, gliosis
** first affected are pyramidal cells of cA1 of hippocampus, layers 3,5,6 of neocortex, purkinje cells and striatal neurons === trouble with memory!
lacunar infarcts
d/t HTN and DM – seen in lenticulostriate aa. or small vessels – small infarcts on basal ganglia
atherosclerosis causing cerebral infarct?
often seen in carotid bifurcation or MCA or basilar aa.
small vessel disease causing cerebral infarct?
d/t HTN or DM or amyloid angiopathy –> results in vessels breaking causing hemorrhagic infarct or vessels causing lacunar infarcts
** occurs in lenticulostriate and mediastriat aa **
anterior chorodal artery small vessel disease
, usually supplies the medial globus pallidus, posterior limb of internal capsule, tail of caudate and optic tract.
** interruption of blood flow from this vessel can result in hemiplegia on the contralateral (opposite) side of the body, contralateral hemi-hypoesthesia, and homonymous hemianopsia
watershed infarct
b/w ACA-MCA or MCA-PCA areas – located at 2 and 3 o’clock
“man in barrel syndrome” areas involving trunk and proximal mm. are most affected
MCA occlusion vs. internal carotid artery?
both cause hemiplegia of that side as well as aphasia
however u/l blindness is only seen in internal carotid occlusion d/t this artery giving off the opthalmic artery
pathology of ischemic stroke
see edema dn loss of gray white matter junction, necrosis, liquefication and cyst formation
microscopic changes: 0-24 hours: red neurons 1-3 days: neutrophils/necrosis 3-10 days: microglia 2-3 weeks: gliosis and neovascularization months: psuedocyts w/ gliotic lining
wallenburg syndrome
lateral medullary syndrome
- PICA syndrome = loss of pain and temp on conralateral side of body and ipsilateral side of face
hemorrhagic strokes
result from rupture of lenticulostriate arteries, often d/t HTN And DM
lobar hemorrhage
think cerebral amyloid angiopathy - often leptomeningeal and cerebral cortical arterioles are affected
d/t accumulation of beta amyloid in the walls, seen w/ AD… and someimtes w/out AD
** Congo Red + depositions **
AVMs
lcoated in SA space -> can cause hemorrhage
port wine staine
sturge-weber syndrome = proliferation of vessels in SA space - can over time cause ischemia
HIE in infants
seen in mature infants - watershed lesions affecting gray matter! b/w MCA/ACA
moderate –> cerebral cortex –> triangular appearance
severe –> cortical and deep nuclei/brainstem damage –> thalamic calcification rimming ventricles
cause: infection, diff. delivery, abruption
PVL
periventricular leukomalacia - seen in preterm infants
ischemic damage to white matter near ventricles!
cause of CP
periventricular region is last to receive O2 b/c vessels grow down from surface
germinal matrix hemorrhage
occus in small babies who have hyaline membrane disease/RDS
symmetrically enlarged cerebral ventricles at 8 months of age!!! w/ seizures
• cause: vessels coming into the base of the brain that infuse the germinal matrix are weak and bleed into the germinal center
Morphology:
• hemorrhage associated with the ventricular wall : starts b/w the thalamus and the caudate nucleus and eventually ruptures into ventricles if large
• often bilateral
porecenephaly
fluid filled cavity confined to brain parenchyma – doesn’t spill into the SA space or ventricular system
schizencephaly
fluid filled clefts – lined by grey matter, can communicate with SA space and ventricular system
hydranencephaly
large obstruction of carotid artery → large portion of cerebrum undergoing autolysis → cyst replaces the whole cerebrum. This transilluminates!
- babies appear normal at first b/c brain stem is intact!
anencephaly
• = incomplete NT fushion, resulting in exposure of the dura and meninges to amniotic fliud → causes destruction of dura as well as underlying cerebrum
o initially the brain is protruding through the cranial vault
o Eventually, all that is left is a small, vascular mass of disorganized neural tissue (cerebrovasculosa) mixed with choroid plexus
o damage to hypothalamus → adrenal hypoplasia
• ~1 in 10,000 births: One of the most common neural tube defects
o Elevated alpha-fetoprotein and acetylcholinesterase in amniotic fluid and maternal blood
o Usually detected on ultrasound
o Folic acid
o incompatible w/ survival
• Anencephaly is often accompanied by spina bifida.
Craniorachischisis:
• most severe NTD, caused by defective closure of the hindbrain-cervical junction – the zipping doesn’t take place throughout the ENTIRE length of cord and head
Myelomeningocele
= Spina bifida
• Herniation of CNS tissue through vertebral defect
• (menigocele is same thing but it does not contain CNS tissue aka meninges)
• Common neural tube closure defect
• Can occur at any level, but»_space; lumbosacral
• Risk of infection
• Some loss of sensation/paralysis
• Folic acid
• Surgical correction
Meningocele = bulge through
defect w/ no CNS protrusion
Cause: failure of closure of NT
and lack of fusion of the vertebral arches, soft tissues and skin that cover the back
encephalocele
• Defect of cranial mesodermal development → Herniation of brain through an axial mesodermal (osseous) defect of the skull
o protruding part gets destroyed b/c of mechanical disruption/ ischemia
o large occipital encephaloceles are incompatible w/ life
o Meninges herniate with (less commonly without) normal brain tissue…tissue in sac gets destroyed
• 75% occipital, less commonly fronto-ethmoidal
Cause/Associations:
• Ciliopathies ??
• Sporadic or associated with other malformations…cardinal feature of Meckel-Gruber syndrome
Meckel-Gruber syndrome
rare lethal cioliopathic AR genetic disorder: MKS1 and MKS3 genes
• occipital encephalocele
• renal cystic dysplasia
• polydactyly
• hepatic development defects
• pulmonary hypoplasia d/t oligohydramnios
hydromelia
(over distension of the central canal):
• = syringomyelia = xs CSF in the central canal of the spinal cord
Symptoms:
• Pain in the neck; shoulders are usually numb
• headaches
• leg or hand weakness
• numbness or loss of sensation in the hands and feet
• problems with walking
• loss of bowel and bladder control
• spasticity and paralysis of the legs
chiari type I
: less severe
• small posterior fossa → herniation of a peg of cerebellar tonsil
• Skeletal abnormalities suggesting that occipital dysplasia is a major pathogenic factor
• There is no neural tube defect
• NOTE: there is no fourth ventricle herniation
Symptoms:
• Asymptomatic or neck pain, lower cranial nerve palsies, sleep apnea, sudden death
• Cerebellar ataxia, late onset hydrocephalus, long tract signs, signs of syringomyelia
• Syringomyelia (90%) – cape like distribution of loss of sensation of pain and temp – tubular cavitation where the central portion of cord gets large and filled with CSF
chiari type II
more severe
• Almost invariably with lumbosacral myelomeningocele
• Craniolacunia: shallow posterior fossa and enlarged foramen magnum, low tentorial insertion→herniation of vermis and tonsils
• Low torcula, short fenestrated falx
• Hydrocephalus (>80%)
Cause:
• small posterior fossa → downward extension of vermis through foramen magnum → hydrocephalus and almost always myelomeningocele (spina bifida)
Symptoms:
• damage results in cerebellar ataxia and loss mm. coordination
o vermis is imp. in mvmt and coordination as well as receiving info of sense and proprioception
o vermis is important in spatial position and movment
• Clinical findings in babies d/t brainstem compression:
o 1) These include stridor secondary to vocal cord paralysis
o 2) Central obstructive apnea
o 3) Swallowing difficulty
o 4) Breath-holding spells
o 5) Hypotonia
• Clinical findings in children:
o 1) Occipital and cervical pain
o 2) Myelopathy with weakness of the upper extremities
o 3) ataxia
o 4) strabismus
o 5) nystagmus;
o 6) defects of smooth pursuit and optokinetic movements
o 7) defect of convergence
o 8) scoliosis
dandy walker malformation
- large posterior fossa with absence of vermis
- usually associated with hydrocephalus (obstruction of CSF flow from fourth ventricle)
- genetically sporadic cause
holoprocencephaly
= cyclops
- absence of cleavage of forebrain, along with external features
- 50% w/ chromosomal anomaly, trisomy 13!!!
- accutane
agenesis of corpus collosum
ACC - asymptomatic! subltle perceptual deficits and some retardation
“bat wings”
PNH
Periventricular Nodular Heterotopia (PNH):
• neurons do not migrate AT ALL from the ventricle: the nodules on the ventricle contain gray matter w/in the ventricular wall
o PNH is characterized by unorganized islands of neurons under the ependyma of the lateral ventricles
lissencephaly
(smooth brain):
• Defective neuronal radial and tangential migration – no normal cortical layers are formed
• Absence of normal convolutions (smooth brain)
• Several underlying genetic abnormalitie -LIS1 mutation
• Some of these genes are associated with microtubule motor proteins and some disrupt microtubule dynamics
• Type I = smooth = complete loss of LS1
• Type 2 = “cobblestone”
polymicrogyria
• cortical organization is disrupted → increased number of gyri – surface shows multiple small bumps
o gray matter has 4 layers or less
o see small, unusually numerous cerebral convolutions
• Diffuse or focal, bilateral or unilateral, symmetric or asymmetric
• Variable neurologic disability
• Seizures, severe psychomotor retardation, spasticity
• Caused by disruptions after neuronal migration
• Intrauterine ischemia, twinning, infections
• Rarely in inherited metabolic syndromes
FCD
Focal cortical dysplasia (FCD):
• FCD is a sporadic developmental malformation of the cerebral cortex that causes intractable seizures and cognitive impairment.
o The core pathology of FCD is an abnormal cortical cytoarchitecture characterized by loss of normal layering.
o loss of layering of germ cells going to the surface, don’t utilize scaffold properly
• **The most frequent pathology in brain tissue removed in epilepsy surgery in children is focal cortical dysplasia. **
• Glioneuronal tumors (ganglioglioma, dysembryoblastic neuroepithelial tumor), vascular malformations, and other lesions are less frequent.
• A significant proportion have hippocampal sclerosis (HS), which is the most frequent lesion in older patients.
CSF in bacterial meningitis
high pressure, high protein, low glucose, lots of polys
CSF in viral meningitis
normal/slightly increased pressure, normal/slightly increased protein, normal glucose, monos present
meningitis birth to 2 mos
E Coli
Group B strep
Listeria
child/adult meningitis
Strep pneumonia Neisseria meningitidis (meningococcus)
elderly meninigitis
Strep. pneumonia
E Coli
Group B strep
Listeria
most common asceptic meningitis?
enterovirus - B71 serotype
herpes encephalitis
inferior frontal and temporal lobes - hemorrhagic necrosis w/ intranuclear inclusions
fatal w/out tx
HIV encephalitis
diffuse infection
• HIV virus infects oligodendrocytes, neurons and microglial cells w/in brain parenchyma
o microglia swallow up HIV and accumulate around vascular area → multinucleated giant cells
CMV
periventricular calcifications - esp. lateral ventricles - prenatal
negri bodies
rabies encephalitis
PML
Progressive Multifocal Leukoencephalopathy (PML): white matter!
• Caused by a polyomavirus JC (one of two ubiquitous viruses, JC and BK)
Histology:
• Reactivation within CNS or in peripheral tissues, with impaired immunity leading to widespread damage of the white matter (oligodendrocytes and astrocytes)
• Infects/destroys oligodendrocytes – axons are left bare
• see intranuclear viral particles – nuclei filled with virions giving it a stippled appearance
Clinical Features:
• Focal neurologic deficits (dysarthria, limb weakness, visual disturbances, ataxia, personality changes, and occasionally seizures)
• Usually progresses relentlessly over a few months, with increasing cognitive impairment
• Almost invariably fatal
• Treatment of underlying immunosuppression (e.g. of AIDS, with highly active anti-retroviral therapy) can lead to remission
SSPE
Subacute Sclerosing Panencephalitis (SSPE): affects gray and white matter!
• caused by measles virus – results in child beginning to have problems in school and behavioral changes
• several months later see seizures and motor problems
• in almost all cases the disease progress to coma and death
• CSF shows increased IgG directed against measles virus
Morphology:
• brain shows diffuse inflammation of grey and white matter
• intranuclear inclusions present with halo
increased IgG to measels seen where?
in MS and in SSPE
cryptococcosis
fungal infection forming abscesses
• Hematogenous dissemination from lung
• Usually in immunosuppression
• Common life-threatening infection in AIDS
Morphology:
• formation of cysts is characteristic!!!
• cysts form in the VR space resulting in VR space dilation
• under microscope see organism with surrounding capsule
• India ink stain illuminates the profile of the organism caused by capsule
ring lesion on CT
think cerebral abscess
cerebral toxoplasmosis
- see multiple abscesses !!!
- Toxoplasma gondii is a protozoan parasite – infection most frequently obtained through oocysts that are shed in cat feces.
- microscopically see many organisms w/in a very thin walled cyst
aspergillosis
- This is one of the more common mycotic infections of the nervous system
- Spores, pulmonary entry
- Hematogenous dissemination
- Causes: Direct invasion, Immunosuppression (leukemia), hemorrhagic Infarcts and abscesses
- Very high mortality rate even with appropriate therapy\
45 degree branching
amoebic abscess
- amoeba transmitted to brain when people go swimming in fresh water, lakes, rivers, pools
- go up the nasal cavity → meninges → brain parenchyma → death
- very difficult to treat!!!
neurocysticercosis
pork tape worm!
- see many cysts throughout brain, both gray and white matter
- most common cause for genealized seizures
• the commonest parasitic infection of the CNS and a leading cause of epilepsy worldwide
• Cysticercus cellusosae, Taenia solium larvae
o Pork meat => patients become definite host
o seen most predominantly in LA, Africa, Asia, Europe
• Cysticercosis: is a tissue infection caused by a young form (cystercus cellulosae) of the tapeworm (Taenia solium)
CJD
abnormal PrSC protiein
beta pleated
see spongiform encephalopathy
gliosis and neuronal death
anti-nmda encephalitis
= AI encephalitis
o often results from pt. having tumor in another part of the body that allows body to make autoAbs against neural antigens – i.e. ovarian teratoma
o Anti-NMDA receptor encephalitis is most frequent in young females with ovarian, mediastinal, and other teratomas, but males with testicular and other teratomas and both sexes with other tumors or without evidence of a tumor may be affected
o immune system sees these neural Ags and respond w/ humoral response by making Abs against neural tissue à they cross the BBB and initiate an AI response against neural tissue initiating an autoimmune encephalitis!
o The most common autoimmune encephalitis is anti-NMDA receptor encephalitis, which, in some studies, is more frequent than HSV and other viral encephalitides.
o It is characterized clinically by psychiatric features, memory disturbance, speech disorder, seizures, dyskinesias, decreased level of consciousness, autonomic instability, and hypoventilation
beta amyloid
think AD or cerebral amyloid angiopathy
tauopathies
AD, Frontotemporal Lobar Degeneration (FTLD), Picks Disease, Progressive Supranuclear Palsy, Corticobasal Degeneration
TDP43
Frontotemporal Lobar Degeneration (FTLD), some forms of ALS
synuclein
o Synuclein (synucleinopathies): Parkinson’s Disease, Dementia with Lewy Bodies Disease, Multiple System Atrophy
AD
progressive memory loss, dysphasia, dyspraxia
beta amyloid plaque formation - initiating event - d/t abnormal beta secretase enzyme - aggregates in neuropil
senile plaques/neurofibrillary tanlges: global loss of gray matter w/ cortical atrophy and large sulci
see tau ghost tangles d/t tau protein accumlation in neurons
CAA
cerebral amyloid angiopathy
deposition of beta amyloid in small vessels –> ischemic lesions and dementia as well as LOBAR hemorrhage
biomarkers for AD?
o CSF: shows decreased Beta amyloid in CSF, with increased Tau deposition in CSF
FTLD
Frontal Lobar Degenerations (FTLD): “tauopathies”
o Picks disease, Progressive Supranuclear Palsy and Corticobasalar Degeneration
** Different from AD in that personality, behavior and language changes appear before memory problems.
Associated with 2 cellular inclusions of cellular proteins.
o FTLD-tau group
o FTLD-TDP43
Morphology:
o causes frontal and temporal degeneration primarily!
o only tau aggregates are present – NO beta amyloid.
o When the tau aggregates look like tangles = FTLD-tau
o When the tau aggregates are smoothed contoured inclusions = Pick disease
PD
• Presents as a hypokinetic movement disorder caused by loss of dopaminergic neurons from the substantia nigra (nigrostriatal system)
** d/t alpha synuclein mutation
• central triad: tremor, rigidity, bradykinesia
Morphology:
• PD is a “synucleinopathy” : like Beta amyloid in AD, alpha-synuclein has been shown to form in aggregates
• abnormal synuclein folds/aggregates in the substantia nigra and is deposited in the cytoplasm of the neurons that are making dopamine that normally have dark brown melanin
• Fibrils made of insoluble polymers of alpha synuclein are deposited in the neuronal body, forming round lamellated eosinophilic cytoplasmic inclusions, the Lewy bodies (LBs).
• LB’s cause neuronal degeneration death especially in the substantia nigra!
DLBD
2nd most common cause of dementia
combines neuro of demtina + parkinsoniasm with fluctuating attention and hallucinations
see Lewy bodies throughout
MSA
Multiple System Atrophy:
• “multiple system” refers to three distinct neuroanatomic circuits that are commonly involved:
o 1) the striatonigral circuit (leading to parkinsonism)
o 2) olivopontocerebellar circuit (leading to ataxia)
o 3) the autonomic nervous system including the central elements (leading to autonomic dysfunction, with orthostatic hypotension as a prominent component).
Morphology:
• see immunoreactive cytoplasmic inclusions in oligodendrocytes containing alpha synuclein
o cell type in MSA is not the neuron, instead it is the oligodendrocyte
o results in myelin problems: white matter degeneration
• characteristically see atrophy of the pons or putamen
• there are no Lewy bodies in the substantia nigra
Huntington disease
chorea/dementia
destruction of caudate and ptame = striatum d/t intranuclear inclusions filled with Huntingtin protein
CAG triplet repeat on 4p16.3 more than 36 repeats
ALS
Amyotrophic Lateral Sclerosis (ALS):
• Is a fatal degenerative disorder of upper and lower motor neurons.
o Lower motor neuron loss causes muscle weakness, atrophy, and fasciculations;
o upper motor neuron involvement causes spasticity, clonus, hyperactive tendon reflexes, and Babinski signs.
o Dementia appears at the onset or develops later in a significant proportion of ALS patients.
majority of patients die, usually from respiratory paralysis, within 2-3 years from the onset of symptoms.
prion-like spread of misfolded proteins SOD-1 (seen in 20% of familial disease) and TDP-43
Morphology:
• loss of LMN’s: atrophy of the anterior horns and motor nuclei of brain stem
• Motor neurons die by Wallerian degeneration with secondary gliosis (grossly = sclerosis)
Clinical features:
• Clinical: progression of weakness over months
FRDA
• Friedreich’s ataxia (FRDA)-
o an autosomal recessive ataxia caused by GAA repeats on the frataxin gene.
o sx: Ataxia, spasticity, weakness, sensory neuropathy, cardiomyopathy.
o occurs in children! 1st decade…hand clumsiness, gait ataxia, pes cavus, diabetes(25%)
o death usually because of CHF/arrhythmias
o NOTE: degenerative disease, NOT a demyelinating disease
• histology shows that there is a loss of axonal white areas but of ganglion cells as well in the dorsal columns and dorsal ganglia
• in image see degeneration of posterior columns, spinocerebellar, corticospinal and other tracts along with atrophy of dorsal roots
• Loss of sensory ganglion cells and degeneration of their axons in peripheral nerves, dorsal roots, and posterior columns deprives the cerebellum of sensory input that is necessary to coordinate movement
ADSCA
• Autosomal Dominant Spinocerebellar ataxias(ADSCAs)-
o a group of autosomal dominant ataxias (25 entities at last count)
o caused by CAG repeats on multiple chromosomal loci
• . If the expansion lies in a coding sequence, it is translated into a polyglutamine (polyQ) stretch of the affected protein.
• Similar to Huntington’s disease (which is also caused by CAG repeats), the ADSCAs show the phenomenon of anticipation, i.e. lengthening of the CAG repeat with earlier onset and more severe disease in successive generations.
• The expansion occurs more often with paternal transmission.
o ** The core neuropathology is cerebellar degeneration
• in add’n to ataxia, they often cause parkinsonism, and extrapyramidal manifestations such as weakness and fasciculations, spaticity and opthalmoplgia, dementia and peripheral neuropathy
MS
• Humoral immunity is involved with production of IgG oligoclonal bands in the CSF → these autoantibodies preferentially attack the myelin sheats
o often results in presence of measles virus IgG in CSF
• Loss of myelin sheath
Histology:
• MS plaques shows inflammation of white matter with lymphocytes with lipid-laden macrophages
o The inflamatory cells in MS include primarily CD8 T-lymphocytes, microglia, and macrohages
• Inactive plaque shows loss of oligodendrocytes, astrocyte proliferation and gliosis causing grossly firm areas (sclerosis)
• NOTE: primarily affects white matter, but results in destruction of surrounding gray matter as well!
• Presentation:
o more common in females
o sensory loss (paresthesias)
o spinal cord: motor dysfunction, cramping, ANS problems such as incontinence
o optic neuritis: presenting sx in 20% of pts – loss of vision or pain on movement
• internuclear opthalmoplegia: interruption of fibers of medial longitudinal fasciulus – thus eye lacks adduction, leading to diplopia
NMO
Neuromyelitis Optica (NMO): Brief discussion
• Bilateral (painful) optic neuritis and spinal cord demyelination, along with intense pain in eye
• Affects women much more than men (even more than MS)
• Poor recovery
• Auto Abs against aquaporin-4, a water channel of astrocytes (can monitor disease response with serum titers)
• Tx: plasmaphoresis +/- anti CD20 Ab therapy
CPM
Central Pontine Myelinolysis (CPM):
• osmotic demyelination syndrome
• occurs in hyponatremic patients when hyponatremia is corrected rapidly and in patients with severe hyperosmolality that was not preceded by hyponatremia.
• The key triggering factor is thought to be a dysosmolar state in the course of which electrolytes and organic osmolytes move out of brain cells into the extracellular space.
• often this change is seen in people, w/ no clinical consequence
• Large lesions cause spastic bulbar paralysis, quadriplegia, stupor or coma, or the locked-in syndrome, developing in a background of severe electrolyte abnormalities.
psamomma body
meningioma
child w/ cerebellar mass, GFAP+ and have long, hairlike processes
pilocytic astrocytoma — only astrocytoma w/out p53 mutation!
** most often occurs in cerebellum!
- well circumscribed w/ solid and cystic component
GFAP positive
** overall good prognosis w/ smal growth
medulloblastoma
Medulloblastomas often occur in the cerebellar midline and are composed of small, round, blue
cells.
most common CNS infection in AIDS?
Toxoplasmosis is a common opportunistic infection that affects the CNS in patients with AIDS. Toxoplasmosis
produces abscesses that organize on the periphery to produce a bright ring on CT and MRI
tumor seen w/ AIDS
cerebral Diffuse Large B cell lymphoma (DLBCL) - d/t IS
d/t EBV virus
Clinical features:
• usually presents with focal neurologic deficits, and appears as enhancing, T2-hyperintense, frequently multiple and bilateral white matter lesions, which may involve the corpus callosum.
• Corticosteroids induce apoptosis in PCNSL cells that may be so profound that the tumors disappear
most common tumor?
meningioma
- also seen w/ radiation in children
- loss of 22q
- arise from arachnoidal cells and are dural based/ extra axial
Clinical features:
• Majority have good prognosis – majority are benign
• complete resection is curative
• >90% WHO I (~5% II, ~2% III) – slow growing tumors
• Many histologic types: note: even though they are low grade, if they grow in the wrong place (i.e. near resp. center) can cause BAD mass effects → death
• pts. present w/ vague nonlocalized sx or d/t compression of underlying parenchyma
morphology:
- circumscribed and well lobulated with twirling pattern, hyalinized calfcified centers w/ psamomma bodies
li fraumeni
syndrome
• TP53/17p
• NS tumor: Astrocytoma
• other tumors: breast cancer, bone and soft tissue sarcoma
NF1 = Von Recklinghausen neurofibromatosis
• NF1/17q
• variety of tumors: o bilateral optic nerve astrocytomas o plexiform neurofibromas o malignant peripheral nerve tumors. • other manifestations: o café au lait spots of the skin,
NF2
- NF2/22q
* NS tumor: Vestibular and PN shwannoma, meningioma, other brain tumors
diffuse astrocytoma
Grade II
• Ill-defined, infiltrating
• Any site in CNS; though > supratentorial (F,T)
Clinical features:
• Seizures, headaches or focal signs
• Tendency to progress to higher grade
• Survival no matter what you do ~5-7 years
Morphology:
• Gross: diffuse and almost hard to visualize
• Micro: see tumor cells that are small and scattered throughout (compare to glioblastoma)
glioblastoma
Astrocytoma Grade IV:
• Most frequent glial tumor in adults – seen most in ages 30-50
• Supratentorial
• loss of PTEN and LOH chromosome 10 is most common mutation in glioblastomas
Clinical Features:
• Highly malignant
• Seizures, headaches, focal deficits
• Survival ~1 year
** Primary vs. Secondary:
• primary glioblastoma is 95% of cases – do NOT see IDH1/IDH2 mutations
• secondary glioblastoma: 5% of cases – indicates that it transformed from lower grade astrocytoma with TP53 mutation – these most frequently have IDH1 and IDH2 mutations — and have a better prognosis!
Morphology:
• high grade astrocytomas/glioblastoma often have leaky vessels present when contrast is injected – this is d/t the fact the neovascularization of tumor cells does not have in tact BBB – thus see “enhancement ring on MRI”
• Micro: see necrosis and many anaplastic small tumor cells around areas of vasculature
IDH1/2
glioblastoma with better pronosis b/c indicative of transformation from low-grade astrocytoma
enhancement ring
seen on glioblastoma — neovascularization results in leaky BBB
“fried egg appearance”
= oligodendroglioma!
Stage II or III
• Ill-defined, infiltrating
• Supratentorial, cortical and white matter
• Frontal lobe in 50-65%
Genetics:
• IDH1/IDH2 gene mutations in 90% and portend a better prognosis.
• Deletions of chromosome 1p, together with 19q seen
Clinical Features: • Most common in 4th-5th decades – slow growing tumors arising in middle aged adults • Long history of headaches, seizures • Prognosis 6 years II – have better prognosis than other gliomas Morphology: • Frequently calcified • See “fried egg” appearance • GFAP +
ex: mass
has small cysts and areas of calcification and hemorrhage. Neurosurgery is performed, and the mass is removed.
Microscopically, the mass consists of sheets of cells with round nuclei that have granular chromatin. The cells have a
moderate amount of clear cytoplasm. These cells mark with GFAP by immunohistochemical staining.
tumor on vermis of cerebellum in child
think medulloblastoma - small blue cells!!!
Stage IV
• Highly malignant tumor of children
o infiltrates and destroys brain tissue and tends to seed the SA space
• 70% IP
• Prognosis: 50-70% at 5 years
• present w/ sx of increased ICP: morning h/a, vomiting, blurred vision, papilledema
• ataxia, strabismus, nystagmus and stiff neck also common
Morphology:
• small blue cell tumor!
• highly cellular tumors, that have small blue cells forming rosettes
• CSF: shows high protein, low glucose and contains tumor cells
majority of BT seen?
metastatic! frequently mutliple, located in periphery of gray matter!
men = carcinoma of lung women = carcinoma of breast
duret hemorrhages
small lineal areas of bleeding in the midbrain and upper pons of the brainstem. They are caused by a traumatic downward displacement of the brainstem - i.e. uncal herniation, etc.
common causes include hippocampal gyrus herniation through the tentorial notch, acute hematoma, edema following trauma, abscess, or tumor.
dimished hearing d/t neoplasm?
think schwannoma = acoustic neuroma - seen at the cerebellopontine angle
nuclear pseudopalisating
nuclear pseudopalisading - aggregation of tumor cells around the periphery of the necrotic areas.
seen in glioblastomas
neoplastic cells within the mass are hyperchromatic
gram + cocci
strep pneumonia - seen in all ages
gram - bacillus
H. influenza, decreased d/t immunization
gram - diplococci
neisseria meningitidis - seen in young adults
short gram + rods
Listeria monocytogenes - seen in epidemics and elderly
gram - bacilli
E. Coli - seen in in neonates and elderly
first cells sensitive to global hypoxia?
hippocampal pyramidal cells
the cerebellar Purkinje cells
superior parasagittal neocortical pyramidal cells are affected
similar to AD, but just frontal and temporal lobe affected, se more behavioral changes rather than loss of memory, along with neurons show intracytoplasmic, faintly eosinophilic, rounded inclusions that stain immunohistochemically for tau
protein.
Pick disease
e4 allele of apolipoprotein E
binds beta amyloid - increased risk of AD
age related macular degeneration
Dry form: drusen forms: accumulation of amyloid in inner side of Bruch’s membrane, can push away photoreceptors form their blood supply resulting in degeneration!
= loss of central vision
Wet form: Age-related macular degeneration (ARMD) is the leading cause of visual loss in the Western world. Its advanced
stages (exudative ARMD) are characterized by extensive choroidal neovascularization that is driven by the local
production of VEGF. Clinical trials now in progress indicate that anti-VEGF agents reduce neovascularization and visual
loss.
ciliary mm.
PS innervation – accommodation
Close vision – when ciliary mm. contracts the ciliary body stretches in length, releasing tension on suspensory ligaments – tension is reduced and lens rounds up
Distant vision – ciliary mm. is relaxed – increased tension on zonular fibers – lens is lengthened
glaucoma
- Open-Angle glaucoma:
• most common form – corneal-iridial angle is open
• usually present with increased IOP – may be d/t increased production or decreased outflow
• tx: prostaglandins, beta blockers, alpha agonists, traceulectomy - Angle closure glaucoma:
• corneal-iridial angle is obstructed and aqueous outflow is impeded
• primary = unknown anatomical cause
• secondary = inflammation, hemorrhage, neovascularization, tumor growth
Increased intraocular pressure is believed to cause the loss of nerve fibers, resulting in a
characteristic cupped excavation of the optic disc.
stye
• acute inflammation usually by Staph – usually clears in 7 days
External stye = infection of sebaceous glands of Zeis at the base of eyelashes (left)
Internal stye = infection of mebonium gland (right)
chalazion
= Meibomian gland lipogranuloma
• Lipogranulomatous inflammatory reaction to sebum in tissues (endogenous “foreign body” reaction)
o Secondary to obstruction of gland
o infection is higher up in the gland -→ rupture of gland results in spillage of lipids
o Epithelioid cells and giant cells surround lipid vacuoles w/ granulomatous response to lipids
• Subacute to chronic and painless nodule
Morphology:
• see empty clear spaces filled with lipids/fats
• see giant cells and lymphocytes surrounding the area, along with granulomas
BCC
most common eyelid malignancy
seen most often in lower lid or areas of middle aspect near nose
flat ulceration, no crater
SCC
shallow ulcer w/ indurated border
elderly fair skinned people
pinguecula
- Asymptomatic, small yellowish submucosal nodule at the limbus
- Adults and older patients but younger if»_space; sun exposure
- Typical in tropical places
- Conjunctival equivalent of Solar Elastosis of skin
- Does not extend to or invade the cornea as a pterygium
Herpes Simplex Keratitis:
- involves the cornea, lesions are painful and large w/ serpintiginous appearance
- inflamm. can get into the interior chamber
- most frequent cause of corneal blindness in US – most common source of infectious blindness as well!
amebic keratitis
hot tubs/contacats
• free living, pathogenic protozoa
Morphology
• Later progresses to a ring ulcer or less commonly as
radial keratitis (see whitish ring discoloration)
• see double walled cyst – often filled with organisms
• Calcoflour white staining can give rapid diagnosis,
confirmed by culture in special medium
Clinical Findings:
• pain, photophobia, decreased vision, injection, irritation, tearing
• often eye pain is worse than clinical appearance
keratoconus
deformation of corneal curvation –> astigmatism
+munson’s sign
retinoblastoma
Rb gene - chromosome 13
Signs/symptoms
• Leukocoria (white pupil), strabismus, red,
• painful eye, poor vision
Morphology:
• see small blue cells w/ rosettes
• on right side see “Flexner-Wintersteiner rosettes”
Treatment: Very aggressive!
sympathetic opthalmia
- immune response against the eyes
- Non-infectious granulomatous inflammation of uvea of both eyes
- Can result from trauma to one eye → retinal antigens become visible to immune system → delayed hypersensitivity reaction in the other eye (and the damaged eye)
- 2 weeks to many years after the
dark pigment in choroid
uveal melanoma –> mets to liver, agressive
Hypertensive retinopathy
from chronic HTN
Findings on funduscopic examination include arteriolar narrowing, flame-shaped hemorrhages, cottonwool
spots, and hard, waxy exudates
arteriosclerotic retoniopathy
Arteriosclerotic
retinopathy causes vascular changes, including arteriovenous nicking and hyaline arteriolosclerosis with “copper-wire”
and “silver-wire” arterioles.
diabetic retinopathy
diabetic retinopathy, including capillary microaneurysms,
cotton-wool spots, arteriolar hyalinization, and more severe changes of proliferative retinopathy with neovascularization.
late stages = retinal detachment!
