Central!Nervous!System!
Pathology!/!Epidemiology!
CNS!Tumors!
General!characteristics!
1.!½!of!all!brain!and!spinal!
cord!tumors!are!
metastatic.!
2.!Most!frequent:!
meningiomas!and!
glioblastoma!multiforme.!
3.!Primary!malignant!CNS!
tumors!account!for!2"3%!
of!all!cancer!deaths!in!the!
US!
Astrocytomas!
Pilocytic!astrocytomas!
Benign!
Grade!1!astrocytoma!
1.!Children!and!young!
adults.!
! aggressive!if!here).!
! 3.!Histologically!classified.!
Ganglioglioma!
Grade!1!astrocytoma!
1.!Children!
!
Definition!/!Presentation!/!Pathogenesis Lab!/!Prognosis!/!Treatment Morphology
1.!Presents!with:!! Prognosis: Primary Metastatic
1.!Headache,!worse!at!night!or!early! 1.!Malignant!CNS!tumors!never!metastasize!outside!the!cranial!cavity.! neuroglial!
morning.! 2.!Consequences!depend!on!location!and!infiltrative!behavior.! tumors!
2.!Seizures,!with!tumors!involving!cerebral! Normal!cortex!histology:! Poorly! Well!
cortex! circumscribed! circumscribed!
3.!Mental!changes!(deficits!in!memory,! Single Multiple
concentration,!reasoning)! Variable! Gray!and!
4.!Neurological!symptoms!related!to! location! white!matter!
involvement!of!specific!brain!regions.! junction.!
5.!Symptoms!related!to!increased!cranial! Neuropil"like Epithelial!
pressure:!CSF!blockage,!tumor!edema! background! appearance!
(peritumoral!edema).! Normal!histology:!!
!
1.!Astrocytes:!large,!irregular!nuclei.!
2.!Oligodendroglial:!uniform!round!nuclei!
1.!Originate!from!astrocytes!and!exhibit! Prognosis: 1.!Located!in!white!matter,!in!centrum!semiovale.
fibrillary!background,!immunoreactivity! 1.!Grading!is!based!on!nuclear!atypia!(pleomorphism),!mitoses,! 2.!Well!differentiated!and!grow!slowly.!
for!GFAP!(glial!fibrillary!acidic!protein),! necrosis,!and!vascular!endothelial!hyperplasia!(VEH)!due!to!increased! 3.!All!low!grade!tumors!can!be!confused!with!reactive!gliosis.!
diffuse!(ill"demarcated)!pattern!of!growth.! production!of!VEGF.! 4.!Grade!2:!moderate!nuclear!pleomorphism!and!no!mitotic!figures.!
Grade!2:!Astrocytoma!–!fibrillary!and!arise!in!the!cerebral!hemisphere! 5.!Grade!3:!similar!to!anaplastic!astrocytoma!but!more!cellular,!
of!young!to!middle"aged!adults!and!in!brain"stem!of!children.!No! pleomorphic,!and!contains!mitotic!figures!
surgical!cure.!
Grade!3:!Anaplastic!astrocytoma!affects!elderly!–!more!cellular,!
pleomorphic!and!contains!mitotic!figures.!
!
!
!
1.!Benign!astrocytic!tumor.! Prognosis: 1. Well"differentiated!arise!throughout!the!neuraxis.
2.!Presents!as!a!cystic!lesion!with!mural! 1.!Favorable!if!in!posterior!fossa!(cerebellum).! 2.!Commonly!located!in!posterior!fossa!(cerebellum)!and!
nodule.! diencephalon.!
3.!Can!also!present!as!a!hypothalamic!or! 3.!Spindly!neoplastic!astrocytes!with!long!bipolar!processes!(hair!like).!
optic!nerve!tumor!(usually!more! 4.!Rosenthal!fibers:!thick!corkscrew"like!eosinophilic!structures,!which!
derive!from!astrocyte!hypertrophic!processes.!
!
1.!Must!present!in!combination!with!an!astrocytic!tumor!cell!population.
2.!Usually!benign!in!the!temporal!lobe!and!with!a!long!history!of!seizures.!
3.!Can!also!be!incidentally!found!(Skier!hits!his!head,!goes!in!for!an!MRI)!
Glioblastoma!multiforme!
(GBM)!
Grade!4!astrocytoma!
1.!Most!common!primary!
CNS!malignancy!in!adults!
Oligodendroglial!tumors!
1.!30"50!yoa.!
Anaplastic!
oligodendroglioma!
Grade!3!
oligodendroglioma!
Ependymoma!
th
1.!4 !ventricle!in!children.!
(papillary!ependymomas)!
2.!Lateral!ventricle!or!
spinal!canal!in!adults.!
Primitive!
neuroectodermal!tumors!
(PNET)!
1.!Develop!in!children!
Primary!glioblastoma:!arises!as!a!
glioblastoma!initially!from!an!EGFR!gene!
amplification.!
Secondary!glioblastoma:!arises!secondary!
to!astrocytoma!progression.!It!begins!as!
an!astrocytoma.!
1.!Glioma!of!oligodendroglial!origin.
2.!Located!in!white!matter!of!cerebral!
hemispheres!next!to!neocortex.!
3.!Manifests!with!seizures.!
4.!Feels!gritty!upon!resection!due!to!
dystrophic!calcifications.!
1.!Hard!to!diagnose!and!classify.!
1.!Glioma!of!ependymal!origin.!
2.!Presents!with!obstructive!
th
hydrocephalus!in!children!(4 !ventricle).!
1.!Highly!undifferentiated!tumors;!
originate!from!a!primordial!neuroglial!
precursor.!
2.!Named!by!location!in!brain.!
3.!Medulloblastoma:!arises!in!the!
cerebellar!vermis!(midline!location)!and!
grows!and!spreads!rapidly!through!CSF.!!
4.!Medulloblastomas!that!occur!below!the!
tentorium!present!with!projectile!
vomiting.!If!under!3!years!old!may!be!
AT/RT!(atypical!teratoid/rhabdoid!tumor)!
with!loss!of!INI1!expression!(INI1!will!be!
present!in!normal!cells)!
Prognosis: 1.!Pleomorphic,!hypercellular!astrocytic!tumor!with!areas!of!tumor!
1.!No!surgical!cure! necrosis!and/or!endothelial!proliferation.!
2.!Endothelial!proliferation:!response!to!trophic!factors!secreted!by!
the!tumor.!
2.!Hallmark:!areas!of!necrosis!surrounded!by!rows!of!neoplastic!cells!
(pseudopalisading!necrosis)!
3.!Butterfly!glioma:!pattern!seen!when!it!crosses!corpus!callosum.!
1.!Grade!2:!Oligodendroglioma 1.!Neoplastic!cells!are!similar!to!oligodendroglia.
2.!Grade!3:!Anaplastic!oligodendroglioma! 2.!Fried!egg"appearance:!pronounced!perinuclear!halo.!
3.!Grade!4:!Glioblastoma!with!oligodendroglial!differentiation.!! 3.!Chicken!wire"pattern:!from!prominent!capillary!network.!
Prognosis:! 4.!Dystrophic!calcifications.!
1.!1p!and!19q!loss!indicates!a!good!prognosis.!
Prognosis: 1.!More!cellular!and!more!pleomorphic!than!oligodendroglioma.
1.!1p!and!19q!loss!indicates!a!good!prognosis.! 2.!Have!tumor!necrosis!and!endothelial!proliferation!as!glioblastoma.!
Prognosis: 1.!Nuclear!free"zone with uniform!round!nuclei
1.!Recur!after!surgery!and!acquire!more!aggressive!behavior,!so!gross! 2.!Ependymal!rosettes:!cells!organized!around!a!lumen.!
total!resection!is!very!important.! 3.!Perivascular!pseudorosettes:!cells!arranged!around!small!vessels.!!
2.!The!spectrum!of!ependymal!tumors!can!range!from!anaplastic!to!
GBM!also.!
!
!
!
Prognosis:! 1.!Blue,!small,!round cell tumors,!with!pseudorosettes with!central!
1.!Highly!aggressive!but!responsive!to!radiation!therapy.! lumen!(Flexner"Wintersteiner!rosette).!
2.!Medulloblastoma:!resection!and!radiation!therapy!–!75%!5!yr.!
survival.!
3.!Atypical!teratoid/rhabdoid!tumor!(AT/RT):!worse!prognosis.!
!
Meningioma! 1.!Tumor!that!originates!from!
1.!Adult!women.! meningothelial!cells!of!the!arachnoid.!
2.!Occurs!most!commonly!
cerebellopontine!angle.!
3.!Atypical!meningiomas!(Grade!2)!have:!
1.!Tumor!necrosis!areas!
2.!Brain!invasion.!
3.!Increased!cellularity!and!nuclear!
pleomorphism.!
! !
!
Schwannoma! 1.!Tumor!that!originates!from!Schwann!
1.!Adults! cells!of!cranial!or!spinal!nerves.!
2.!Most!frequently!at!CN8!at!
cerebellopontine!angle.!
3.!Can!also!occur!in!periphery!as!well.!
4.!Presents!with!hearing!loss!and!tinnitus.!
Pituitary!adenoma! 1.!Presents!with!endocrine!disturbance,!
1.!Adults! mass!effect!(bilateral!temporal!
hemianopsia)!
Huntington!disease!(HD)! 1.!Autosomal!dominant!disorder!
Caudate! characterized!pathologically!by!
1.!Affects!NW!European! degeneration!of!GABA"nergic!neurons!of!
descent.! the!caudate!nucleus!and!clinically!by!
2.!No!new!mutations.! chorea!and!dementia.!
3.!Incidence!in!high! Presents:!!
prevalence!regions!is! 1.!Presents!between!30"50!with!subtle!
1/12,000"20,000.! movement!abnormalities!(fidgeting)!and!
personality!change!(mentation).!
2.!Eventually!the!chorea!and!personality!
changes!become!obvious.!
Lab: 1.!Attached!to!dura,!pushes!underlying!brain!without!invasion.
1.!EMA!(epithelial!membrane!antigen)!positive.! 2.!Fibrous!meningioma!(Grade!1):!Spindle"shaped!cells!with!indistinct!
Prognosis:! borders!(syncytial).!
1.!Generally!good.! 3.!Transitional!meningioma!(Grade!1):!Whorls!or!fascicle!arrangement!
2.!Tumors!at!some!locations!may!not!be!able!to!be!resected.! of!cells.!
3.!Worse!prognosis!if!papillary!meningioma!(Grade!3)!or! 4.!Psamomma!bodies!occur!when!whorls!degenerate!and!calcify.!
hemangiopericytomas.!(Grade!2).! 5.!Grade!II:!areas!of!tumor!necrosis,!brain!invasion,!increased!
4.!Also!bad!prognosis!if!mitotic!figures!are!seen.! cellularity!and!nuclear!pleomorphism.!
! Transitional!meningioma:!
!
!
Lab: 1.!Spindly!cells!arranged in!hypercellular!Antoni!A!areas!(elongated,!
1.!S"100!positive! cigar"shaped!nuclei),!alternating!with!Antoni!B!areas!(loose!vacuolated!
Prognosis:! tumor).!
1.!Good!after!surgical!resection! 2.!Verocay!bodies:!parallel!rows!of!neoplastic!Schwann!cells.!
2.!If!it!becomes!malignant!it!is!called!a!malignant!peripheral!nerve! 3.!Difficult!to!distinguish!fibrous!meningioma!from!Schwannoma,!a!
sheath!tumor.! reticular!stain!can!identify!the!Schwannoma.!
Prognosis: 1.!Normal:!Presence!of!a!mixture!of!acidophils,!basophils,!and!
1.!Usually!not!malignant.! chromophobe!cells!in!a!glandular!pattern!with!capillaries!surrounding!
2.!If!malignant,!destruction!of!bone!can!result.! the!pituicytes.!
2.!Adenoma:!loss!of!glandular!architecture!and!monomorphic!
composition.!
Genetics: 1.!Atrophy!of!the!caudate!nucleus with!secondary ventricular!dilation!
1.!HD!gene!(huntingtin!gene)!is!on!chr.!4.! (hydrocephalus!ex!vacuo).!
2.!Mutations!are!due!to!unstable!trinucleotide!repeat!expansion.!! 2.!Loss!of!small!neurons!in!the!caudate!nucleus!followed!by!larger!
3.!Shows!features!of!anticipation!and!imprinting.!! neuron!loss.!
4.!Loss!of!neurons!(GABA"nergic)!removes!inhibitory!influences!on!
extrapyramidal!circuits!leading!to!chorea.!
Treatment:!
1.!Antipsychotic!drugs!(haloperidol)!
Testing:!
1.!Genetic!testing!is!available.! !
!
Alzheimer!disease!(AD)! 1.!Risk!factors:!aging,!head!trauma,! Genetics!of!AD:!Most!cases!are!sporadic. 1. Pan"lobar!cortical!atrophy!with!narrowed!gyri!and!wide!sulci!mostly!
Cortical! familiarity.! 1.!Amyloid!precursor!protein!(APP)!gene!–!chr.!21:!All!Down!syndrome! of!hippocampus!and!temporal!lobes,!with!occipital!sparing.!!
1.!60%!of!all!dementia! 2.!Protective!factors:!High!level!of! patients!develop!AD!in!their!30s!due!to!3!copies!of!APP!gene.! 2.!Hydrocephalus!ex!vacuo:!dilation!of!ventricles!from!loss!of!brain!
cases! education,!smoking.! 2.!Presenilin"1!gene!–!chr.!14:!majority!of!hereditary!cases.!Presenilin"2! parenchyma.!
2.!Incidence:!2%!at!65!yoa! 3.!Genetic!factors:!5"10%!of!AD!cases!are! gene!(chr.!1)!can!be!present!as!well.!! 3.!Lesions!involve!neocortex,!hippocampus,!subcortical!nuclei,!
doubles!every!5!years! hereditary,!early!onset,!and!transmitted! 3.!Apolipoprotein!E!gene!–!chr.19:!E4!increases!risk!and!is! including!forebrain!cholinergic!(basal!nucleus!of!Meynert)!nuclei.!
after.! autosomal!dominant.! overrepresented!in!AD!patients!but!is!still!late!onset.!E2!is!
! 4.!No!diagnostic!test!for!disease,!diagnosis! underrepresented!and!confers!protection.!!
of!exclusion.! Protein!accumulation!(presence!does!not!indicate!but!quantity!of!
Presents:! plaques!and!tangles):!
th th
1.!Insidious!onset!beginning!in!7 "8 ! 1.!A"beta!amyloid:!peptide!from!amyloid!precursor!protein!(APP).!Is!
decade.! produced!by!enzymatic!cleavage!by!gamma"secretase!(!a!potential!
2.!Progressive,!slow!memory!impairment,! target!for!treatment!by!blocking!activity)!
especially!recent!events.! 2.!Tau!–!chr.!17:!microtubule!protein!that!does!not!confer!AD!but!can!
3.!Mood!and!behavior!alteration.! increase!risk!of!getting!other!neurodegenerative!diseases.!
4.!Disorientation.! 3.!Neuritic!tangles!(NT):!A"beta!amyloid!core!surrounded!by!dystrophic!
5.!Aphasia!(language!skill!loss)!and!apraxia! processes!from!microglia!and!astrocytes.!
(motor!skill!loss)! 4.!Neurofibrillary!tangles!(NFT):!aggregates!of!insoluble!cytoskeleton!
6.!Mute!and!bedridden!in!5"10!years.! composed!of!abnormally!phosphorylated!tau!"!forming!paired!helical!
elements!(PHF).!
5.!Cerebral!amyloid!angiopathy!(CAA):!A"beta!amyloid!accumulation!in! !
media!of!intracortical!and!leptomeningeal!arteries,!can!progress!to!
hemorrhage!and!occur!by!itself.!
6.!Granulovaculolar!degeneration!(GVD)!and!Hirano!bodies!(HBs)!
develop!in!hippocampus!but!are!less!significantly!diagnostic.!!
Treatment:!!
1.!None!but!acetylcholinesterase!inhibitors!show!mild!improvement.!
2.!NMDA!receptor!antagonists.!
3.!Immunization!against!A"beta!peptide!(autoimmune!encephalitis!may!
occur)! !
4.!Gamma"secretase!inhibitors!
Amyotrophic!lateral! 1.!Degeneration!and!loss!of!upper!and/or! Prognosis: 1.!Ventral!spinal!motor!nerve!roots!and!cranial!motor!nerves!are!
sclerosis! lower!motor!neurons.! 1.!Death!often!results!from!respiratory!failure.! atrophic!compared!to!sensory!nerve!roots.!
Motor!system! 2.!Betz!cells:!upper!motor!neurons!in! Diagnosis:! 2.!TDP"43!inclusions!can!be!seen!in!neocortex,!hippocampus,!and!
1.!40"70!yoa.! primary!motor!cortex!and!their!axonal! 1.!Biopsy!of!muscle!reveals!fiber!type!grouping!and!grouped!atrophy! lower!motor!neurons.!
extensions!in!the!corticospinal!tracts! (neuropathic!myopathy).!
produce!hyperreflexia,!spasticity.! Genetics!and!MCB:!
3.!Lower!motor!neurons!(more!common):! 1.!SOD1!–!chr.!21:!mutation!in!gene!for!superoxide!dismutase.!
loss!produces!weakness,!atrophy,!and! 2.!TDP"43:!inherited!form,!mutation!in!a!DNA/RNA"binding!protein.!
fasciculations.! 3.!FUS/TLS:!another!DNA/RNA!binding!protein!that!also!triggers!
premature!degeneration!of!motor!neurons.!
!

Friedreich!ataxia! 1.!Autosomal!recessive!disorder!leading!to! Genetics: Degeneration:

Spinocerebellar! degeneration!of!nerve!tissue!in!spinal! 1.!Due!to!expansion!of!unstable!triplet!nucleotide!repeat!(GAA!repeats! 1.!Dorsal!root!ganglia.!
degeneration! cord,!especially!the!sensory!neurons! in!the!first!intron)!in!the!frataxin!gene!on!chr.!9.! 2.!Clarke!column!(origin!of!spinocerebellar!tract).!
1.!Onset!in!early! connected!to!cerebellum!affecting!muscle! 2.!Frataxin!protein!is!essential!for!mitochondrial!function!by!helping!in! 3.!Neurons!of!posterior!column!of!spinal!cord.!
childhood.! movement!of!arms!and!legs.! mitochondrial!iron!regulation,!and!in!the!absence!of!frataxin,! 4.!Cranial!nerves!7,!10,!and!12.!
2.!Wheelchair!bound!by!5! Presents:! mitochondrial!iron!builds!up,!leading!to!free!radial!damage!and! 5.!Dentate!nucleus!and!Purkinje!cells!of!cerebellum.!
yoa.! 1.!Gait!ataxia,!dysarthria,!hand!clumsiness,! mitochondrial!dysfunction.! 6.!Betz!neurons!of!primary!motor!cortex.!
loss!of!positional!sense,!vibratory!sense,!
and!tendon!reflexes.!!
Parkinson!disease!and! 1.!Loss!of!dopaminergic!neurons!in! Etiology: 1.!Histologic!hallmark of!idiopathic!Parkinson!disease!is!the!Lewy!body!
syndrome! substantia!nigra.!! 1.!Loss!of!dopaminergic!neurons!in!idiopathic!Parkinson!disease.! –!eosinophilic!cytoplasmic!inclusion!and!is!composed!of!alpha"
Midbrain! 2.!Tremor,!rigidity,!and!akinesia.! 2.!Parkinson!syndrome!can!be!diagnosed!when!levodopa!does!not! synuclein!(plays!a!role!in!synaptic!plasticity).!
1.!Common!(2%!of! 3.!Disease!is!idiopathic!(most!common).! work.!
population)! 4.!Syndrome!is!due!to!injuries!to! 3.!Post"encephalic!Parkinson!disease:!is!an!autoimmune!disorder!
th th
2.!5 !to!8 !decade.! substantia!nigra.!! associated!with!an!influenza!pandemic.!
Presents:! 4.!Multiple!system!atrophy:!synuclein!in!the!glia!define!this!disease!
1.!Slowing!of!all!voluntary!movements! and!it!describes!striatonigral!degeneration!(putamen),!
nd
2.!Tremor!at!rest!that!disappears!during! olivopontocerebellar!atrophy,!and!Shy!Drager!syndrome.!It!is!the!2 !
movement.! most!common!cause!of!Parkinsonism,!and!is!considered!when!
3.!Expressionless!face.! treatment!for!idiopathic!Parkinson!does!not!work.!!
4.!Rigidity!of!limbs!and!trunk!with!inability! 5.!Progressive!supranuclear!palsy:!tauopathy,!globosa!tangles!in!basal!
to!initiate!voluntary!movements.!! ganglia,!brainstem!(occulomotor!cortex).!Characterized!by!
5.!Increased!incidence!of!dementia!and! Parkinsonism!and!supranuclear!opthalmoplegia!(INO).!Presents!with!
depression.! frontotemporal!dementia.!
! 6.!MPTP:!1"methyl"4"phenyl"1,!2,!3,!6"tetrahydropyridine!is!a! !
contaminant!in!synthetic!heroin!and!causes!rapidly!progressive! !
Parkinson.!
Genetics:!
1.!PARK1!"!AD!(chr.!4):!Synuclein!mutations!have!Lewy!bodies.!
2.!PARK2!"!AR!(chr.!6):!Parkin!interacts!with!an!ubiquitin"conjugating!
enzyme!E2!which!plays!a!role!in!protein!degradation!via!proteasome.!
3.!PARK3!–!AD!(chr.!2)!
4.!PARK4!–!AD!(chr.!4):!synuclein!triplication.!
5.!PARK5!–!AD!(chr.!4):!UCH"L1!–!ubiquitin!hydrolase!mutation!that!is!
expressed!in!high!levels!in!neurons!which!plays!a!role!in!degradation!
via!proteasome.!
6.!PARK6!–!AR!(chr.!1):!PINK1,!early!onset!due!to!this!serine/threonine!
kinase!domain!which!is!induced!by!PTEN.!
7.!PARK7!–!AR!(chr.!1):!DJ1,!early!onset!due!to!low!mRNA!stability.!!!
Treatment:!
1.!Levodopa!is!drug!of!choice.!
!
Pathology!/! Definition!/!Presentation!/!Pathogenesis! Lab!/!Prognosis!/!Treatment! Morphology
Epidemiology!
Pick’s!disease! Presents:! Genetics:!
Corticobasal! Frontotemporal!dementia!(2!variants):! 1.!FTDP"17:!are!familial!dementias!cause!by!tau!mutations!(frontotemporal!
degeneration! 1.!Behavioral:!loss!of!empathy,!apathy,!changed!in!food!preference! dementia!and!parkinsonism)!associated!with!chromosome!17!and!do!not!
Cortical! appetite,!stereotypic!and!repetitive!behaviors,!disinhibition,!blunting,!poor! have!substantial!numbers!of!plaques!and!tangles.!
Progressive! self"care.! Tau:!microtubule!binding!protein!with!several!microtubule!binding!domains.!
supranuclear!palsy! 2.!Progressive!non"fluent!aphasia!(PNFA)!or!semantic!dementia:!orobucal! 3"repeat!tau:!Pick’s!disease!
Midbrain! apraxia,!impairment!of!semantic!memory,!spoken!written!word! 4"repeat!tau!(have!exon!10!included):!cortical!basal!degeneration!and!
comprehension,!impoverished!fund!of!general!knowledge.! progressive!supranuclear!palsy.! !
3.!Preservation!of!perceptual!skills!and!non"verbal!solving!and!day"to"day! Mixed!3,4"repeat!tau:!Alzheimer’s!disease! 1.!Pick’s!disease:!profound!
memory.! Frontotemporal!cortical!atrophy.!
Corticobasal!degeneration:! 2.!Progressive!supranuclear!palsy:!
1.!Usually!around!60!yoa.! Globose!tangles!
2.!Asymmetrical!clumsiness,!stiffness.!
3.!Limb!movement!without!control.!
Progressive!supranuclear!palsy:!!
1.!Parkinsonism!and!supranuclear!opthalmoplegia!(loss!of!movement!of!
eyes).!
!
!
Trauma!and!vascular!diseases!
Pathology!/!Epidemiology!
Intracranial!pressure!
Overview!
Subfalcine!herniation!
Definition!/!Presentation!/!Pathogenesis Lab!/!Prognosis!/!Treatment Morphology
Presents:! Lab:
1.!Headache! 1.!Normal!ICP:!!<!15!mmHg.!
2.!Depressed!global!consciousness!from! 2.!Intracranial!hypertension!(ICH):!>20!mmHg.!
midbrain!involvement.! 3.!High!intracranial!pressure!is!usually!due!to!an!acute!problem,!
3.!Vomiting.! not!chronic.!!
4.!Abducens!nerve!palsy! Treatment:!!
5.!Papilledema! 1.!ICP!monitoring! !
6.!Periorbital!bruising.! 2.!Mannitol!
7.!Cushing’s!triad:!bradycardia,!depressed! 3.!Steroids!
respiration,!hypertension.! 4.!Hyperventilation!
1.!Occurs!supratentorially!in!one!hemisphere!resulting!in!a!midline!shift!of!structures!toward!the!opposite!side.
Presents:!
1.!Anterior!cerebral!artery!compression:!weakness!and!sensory!loss!in!one!or!both!legs.!

Uncal!herniation! 1.!Uncus!of!the!temporal!lobe!is!displaced!over! Complications:

Transtentorial!
Tonsillar!herniation!
Epidural!hematoma!
1.!Commonly!the!middle!
meningeal!artery!
Subdural!hematoma!
1.!Elderly!patients!
Subarachnoid!hematoma!
the!free!edge!of!the!tentorium.!
Presents:!
1.!Eye!rests!at!down!and!out!with!dilated!pupil!
(mydriasis)!
2.!Compression!of!posterior!cerebral!artery!
may!result!in!visual!disturbances.!
! extending!to!contralateral!cerebral!peduncle.!
1.!Displacement!of!cerebellar!tonsils!through!
the!foramen!magnum.!
1.!Usually!from!trauma!(skull!fracture),!occurs!
above!the!dura.!
2.!Present!in!a!coma!secondary!to!brain!
compression!by!hematoma!with!a!possibility!of!
dilated!pupil.!However!does!have!a!short!lucid!
interval!with!consciousness!before!onset!of!
coma.!
3.!If!patient!comes!in!conscious!with!head!
injury,!then!hold!for!observation!for!24!hours.!
1.!Usually!from!trauma!resulting!in!fracturing!of!bridging!veins!and!occurs!below!the!dura.
Presents:!
1.!With!mild!trauma!with!little!loss!of!consciousness!with!symptoms!hours!to!days!later.!
1.!Caused!by!ruptured!berry!aneurysms!or!
arteriovenous!malformation.!
Presents:!
1.!Worst!headache!of!my!life.!
1.!Duret!hemorrhages:!hemorrhages!in!pons!and!midbrain!
caused!by!herniated!tissue!pushing!brainstem!further!down!into!
posterior!fossa,!can!be!accompanied!with!posterior!cerebral!
artery!compression.!
2.!Kernohan’s!notch!phenomenon:!contralateral!pupillary!
dilation,!ipsilateral!weakness,!resulting!from!herniation!
!
Differential!for!Duret!hemorrhages:!
1.!Central!pontine!myelinolysis:!neurological!disease!caused!by!
severe!damage!of!myelin!sheath!of!nerve!cells!in!brainstem.!
Complications:
1.!Compression!of!medulla:!cardiorespiratory!arrest.!
2.!Compression!of!midbrain:!trouble!looking!up.!
Prognosis:!
1.!Tonsillar!herniation!usually!results!in!death.!
Complications:
1.!Leads!to!subfalcine!herniation!if!not!promptly!evacuated.!
Treatment:!
1.!Burr!holes!to!evacuate!blood.!
Prognosis:!
1.!Recurs!frequently.! !
Prognosis:
1.!Initially!small!bleeding!to!large!amount!which!can!result!in!
death.!
Treatment:!
1.!Surgical!or!arteriovenous!resection.!
Intraparenchymal!hematoma!
Amyloid!angiopathy!
Congophilic!angiopathy!
Transient!ischemic!attack!
Stroke!
Cerebral!infarction!
1.!85%!of!stroke!cases.!
2.!Most!often!due!to!cerebral!
vessel!occlusion.!
Contusions!
Diffuse!axonal!injury!
Arteriovenous!malformations!
1.!Males!10"30!yoa.!
2.!Commonly!occurs!with!
middle!cerebral!artery!
(posterior!branches).!
Cavernous!angioma!
! intervening!nervous!tissue.!!
Capillary!telangiectasia!
1.!Usually!from!hypertension!and!involves! Complications:
basal!ganglia!but!can!also!involve!the! 1.!If!it!occurs!in!pons!the!patient!will!immediately!go!into!a!
cerebellum,!pons,!and!centrum!semiovale.! coma!and!death.!
Treatment:! !
1.!Surgical!evacuation!of!the!hematoma.!
1.!Same!amyloid!that!forms!plaques in!Alzheimer’s and!causes!weakness!in!the!wall!with!eventual!hemorrhage.
2.!Hemorrhage!is!cortical!or!subcortical.!!
1.!Reversible,!symptoms!last!less!than!24!hours;!and!due!to!small!platelet!thrombi!or!atheroemboli.!
2.!Does!not!result!in!death!of!tissue.
1.!May!become!hemorrhagic!(15%)!due!to!reperfusion.
2.!Infarction!(85%!of!stroke!cases)!!
3.!Causes!death!of!tissue.!
Embolic!occlusion:! Complications: 1.!Results!in!liquefaction!necrosis!with!grayish!discoloration,!
1.!Often!due!to!thromboemboli!from!cardiac! 1.!Penumbra!(an!area!between!damaged!core!and!normal!brain)! congestion,!and!edema.!
chambers!leading!to!hemorrhagic!infarct.! can!progress!to!infarction!from!excitotoxicity.!! 2.!Gliosis!(reactive!hypertrophy!of!remaining!astrocytes)!may!occur!
2.!If!it!affects!anterior!and!middle!cerebral!the! Treatment:! around!central!necrosis.!
emboli!is!in!the!internal!carotid!artery.! 1.!Preserve!ischemic!penumbra.! 3.!Inflammation!may!occur!with!PMNs!initially!and!macrophages!
later.!
1.!Lesions!associated!with!direct!parenchymal!injury!of!the!brain!either!through!transmission!of!kinetic!energy!to! 1.!Usually!wedge!shaped!with!a!broad!base!lying!along!the!surface,!
the!brain!and!bruising.! deep!to!the!point!of!impact.!
2.!Leads!to!rapid!tissue!displacement!disruption!of!vascular!channels,!and!subsequent!hemorrhage,!tissue!injury! 2.!Earlier!stages!there!is!pericapillary!edema!and!hemorrhage.!
and!edema!with!the!crests!of!the!gyri!being!the!most!susceptible.! 3.!!Later!stages!the!blood!extends!throughout!the!involved!tissue.!
3.!Commonly!occur!on!the!frontal!and!temporal!lobes.! !
4.!Coup!injury:!contusion!at!the!point!of!contact.!
5.!Contrecoup:!contusion!on!the!brain!surface!diametrically!opposite!to!point!of!contact.!
1.!Caused!by!angular!acceleration!in!the! Complications:! 1.Usually!affects!deep!white!matter!regions!(corpus!callosum,!
absence!of!impact.! 1.!50%!develop!coma!after!trauma.! hippocampus,!peduncles,!colliculi).!
1.!Involve!vessels!in!the!subarachnoid!space! Treatment:
extending!into!the!brain!parenchyma!and! 1.!Surgical!resection!preceded!by!embolization!to!prevent!
involves!a!network!of!wormlike!vascular! massive!bleeding.!
channels!with!arteriovenous!shunting!of!high!
flow!blood.!
Present:!!
1.!Worse!headache!of!my!life!and!can!be!
associated!with!a!seizure.!!
1.!Consist!of!greatly!distended,!loosely!organized!vascular channels!with!thin,!collagenized!walls!and!are!devoid of! 1.!Occur!in!the!cerebellum,!poins,!and!subcortical!regions.
2.!Contain!microscopic!deposits!of!hemosiderin.!
1.!Dilated!capillaries!with!intervening brain!parenchyma.
Presents:!
1.!Asymptomatic,!commonly!presenting!as!incidental!autopsy!finding.!!
Berry!aneurysm!
1.!Most!commonly!occurs!at!
anterior!communicating!artery!
or!middle!cerebral!artery.!
th
2.!Female,!5 !decade.!
Watershed!infarcts!
1.!Area!between!anterior!and!
middle!cerebral!artery!is!at!
greatest!risk.!
Other!neuropathology!topics!
Pathology!/!Epidemiology!
Multiple!sclerosis!
rd th
1.!Women!in!3 !or!4 !decade.!
Dermatomyositis!
1.!Children!or!adults.!
Polymyositis!
1.!Adults!
Inclusion!body!myositis!
1.!>50!yoa.!
1.!Most!common!cause!of!clinically!significant! Prognosis:
st
subarachnoid!hemorrhage.!! 1.!25"50%!dies!with!1 !rupture,!repeat!bleeding!can!occur!and!
Presents:! decreases!prognosis!every!time.!
1.!Rupture!occurring!when!straining!at!stool!or! Complications:!
sexual!orgasm!and!presenting!with!worst! 1.!Sequelae!are!associated!with!healing!process.!
headache!of!my!life,!and!then!rapidly!losing! 2.!First!few!days!there!is!increased!risk!for!vasospasm!induced!
consciousness.!! ischemic!injury.!
3.!Healing!phase!involves!meningeal!fibrosis!and!scarring!
leading!to!CSF!obstruction.!
1.!Occur!in!regions!of!brain!and!spinal!cord!that! 1.!Brain!is!swollen!with!widened!gyri!and!narrow!sulci.!
lie!at!the!most!distal!reaches!of!arterial!supply.! Morphological!changes:!
Presents:! 1.!Early:!12"24!hours,!microvaculoization,!then!eosinophila!of!
1.!Some!may!present!with!bilateral!leg! neuronal!cytoplasm,!and!later!pyknosis,!and!karyorrhexis.!Most!
weakness!if!motor!involvement.!! susceptible!are:!pyramidal!CA1!cells!and!Purkinje!cells.!!
Adults:! 2.!Subacute!changes:!24!hours"2!weeks,!necrosis,!macrophage!
1.!Neurons!are!most!vulnerable! influx,!vascular!proliferation,!and!reactive!gliosis.!!
Perinatal:! ! 3.!Repair:!2!weeks,!necrotic!tissue!removal,!loss!of!CNS!structure!
!
1.!White!matter!is!most!vulnerable.! and!gliosis.!!
4.!Pseudolaminar!necrosis:!neuronal!loss!and!gliosis!producing!an!
uneven!desctruction!of!the!neocortex,!with!preservation!of!some!
layers!and!invovlement!in!others.!
Definition!/!Presentation!/!Pathogenesis Lab!/!Prognosis!/!Treatment Morphology
1.!Chronic!relapsing"remitting!disorder of!probable!autoimmune!origin!characterized!by! Complications:
recurrent!episodes!of!demyelination!in!the!brain!(including!optic!nerves)!and!spinal!cord,! 1.!Progression!to!cystic!lesions!
which!results!in!progressive!neurological!deficits.!!
2.!Diagnosis!is!based!on!the!presence!of!multiple!lesions!separated!in!both!space!and!
time!and!most!commonly!at!the!angle!of!the!ventricle.!
Presents:!
1.!Waxing!and!waning!motor!symptoms!
2.!Blurred!vision!or!loss!of!vision!in!one!eye.!
!
3.!Diplopia!and!vertigo.! 1.!Can!have!perivascular!lymphocytes!in!
4.!Loss!of!sensation!or!weakness!in!one!leg.!! demyelinated!plaques.!!
5.!Hemiparesis!or!loss!of!sensation!in!half!of!the!body.!! 2.!Loss!of!myelin!occurs!with!axonal!
! preservation.!
1.!Inflammatory!disorder!of!the!skin!as!well!as!skeletal!muscle. Lab:
Presents:! 1.!Increased!creatine!kinase.!
1.!With!a!skin!rash!that!accompanies!or!precedes!the!onset!of!muscle!disease.! Treatment:!
2.!Rash!occurs!on!eyelids!with!periorbital!edema!and!with!accompanying!red!patches! 1.!Corticosteroids.!
over!the!knuckles,!elbows,!and!knees!(Grotton!lesions).!! Prognosis:!
3.!Muscle!weakness!is!of!slow!onset!and!symmetric!with!myalgias!and!typically!affects! 1.!Increased!risk!of!lung,!
the!proximal!muscles!first.!! stomach,!and!ovarian!cancers.!
!
!
1.!Perimysal!and!vascular!lymphocytic!
inflammation.!
1.!Characterized!by!symmetrical muscle involvement!without!cutaneous!involvement!but!may!also!have!inflammatory! 1.!Endomysial lymphocytic!inflammation!
involvement!of!heart,!lungs,!and!blood!vessels.! mostly!cytotoxic!CD8!T"cells.!
2.!Caused!by!cell!mediated!injury!of!myocytes!with!CD8!and!cytotoxic!T"cells!around!damaged!muscle.! 2.!Skeletal!fiber!degeneration!and!
3.!Presents!with!bilateral!proximal!muscle!weakness.! regeneration.!
Presents:! 1.!Cytoplasmic!vacuoles!with!basophilic!granules!and!amyloid.
1.!Asymmetrical!distal!muscle!weakness! 2.!Filamentous!inclusions!on!EM.!
Duchene!muscular!dystrophy!
1.!Most!common!and!severe!form!of!
muscular!dystrophy.!
2.!X"lined!(males)!
3.!Mutation!in!dystrophin!gene!on!X!
chromosome!results!in!absence!of!
dystrophin!protein.!
!
Infections!
Definitions!
Acute!bacterial!meningitis!
1.!Most!common!infection!of!CNS.!
2.!0"2!months:!E.Coli,!Group!B!Strep,!Listeria.!
3.!2!months!–!5!yrs.:!Streptococcus!pneumonia,!
meningococcus.!H.influenzae!very!common!before!
vaccine.!
4.!5!yrs.!"!adult:!Streptococcus!pneumonia,!N.meningitidis.!
5.!Elderly:!Streptococcus!pneumonia,!E.Coli,!Group!B!Strep,!
Listeria!
Acute!viral!(aseptic)!meningitis!
1.!Commonly!caused!by!enteroviruses.!
Cryptococcal!meningitis!
Subacute!sclerosing!panencephalitis!
1.!Rare!
2.!Occurs!in!children!and!adolescents.!
3.!Previous!infection!of!measles!before!age!2.!
Nerve!biopsy!uses!
1.!A!severe!recessive!X"linked!form!of!muscular!dystrophy!leading!to!rapid!progression!of! Prognosis:
muscle!degeneration.! 1.!Death!in!early!20s.!
Presents:! Lab:!
1.!Manifests!at!5!yoa!with!wheelchair!dependence!by!10"12.! 1.!Increased!creatine!kinase.!
2.!Progressive!muscular!weakness! Diagnosis:!
3.!Calf!pseudohypertophy.! 1.!Muscle!biopsy:!immunostains! !
4.!Proximal!weakness!of!shoulder!and!pelvic!girdles.! show!decreased!dystrophin! 1.!Trichrome!stain!
5.!Heart!failure!and!arrhythmias!may!occur.! protein.! 2.!Muscle!fibers!of!various!sizes!
6.!Respiratory!insufficiency!and!pulmonary!infections!due!to!decreased!muco"cilary! 2.!DNA!analysis!by!PCR.! 3.!Necrosis,!degeneration,!and!regeneration!
clearance.! of!fibers.!
! 4.!Fibrosis!
5.!Fatty!infiltration.!
1.!Meningitis:!infection!of!subdural!space. CSF!Lab!values:
2.!Encephalitis:!viral!infection!of!the!brain.! 1.!Bacterial!or!fungal:!Increased!neutrophils,!decreased!glucose,!and!
3.!Encephalomyelitis:!infection!of!the!brain!and!spinal!cord.! highly!increased!pressure!(>200),!increased!protein!(45"200)!
4.!Meningoencephalitis:!infections!of!the!subarachnoid!space!and!brain!parenchyma.! 2.!Viral:!Increased!lymphocytes,!no!change!in!glucose,!and!slightly!
increased!pressure.!
Presents: Complications:
1.!Acute!onset!in!hours.! 1.!Hydrocephalus!(from!
2.!Fever,!lethargy,!headache,!altered!mental! inflammatory!cells!in!
status.! subarachnoid!space)!
3.!Nuchal!rigidity!(neck!stiffness),!cloudy! 2.!Cranial!nerve!impariment.!
sensorium,!coma,!death.!
!
1.!Gross:!thick!exudate,!coating!surface!of!brain.!
2.!Micro:!thick!layer!of!PMNs!in!subarachnoid!space!
Presents: Prognosis: 1.!Lymphocytic!infiltration!of!leptomeninges!and!superficial!cortex.!
1.!Fever,!lethargy,!headache,!altered!mental! 1.!Low!mortality.!
status.!
2.!Depressed!consciousness.!!
1.!Invasion!of!brain!through!Virchow"Robin!space"continuation!of!subarachnoid!space! 1.!Soap!bubble!lesions,!seen!with!India!ink.
around!blood!vessels!entering!neuropil.!
Presents:!
1.!Fever,!lethargy,!headache,!altered!mental!status.!
Presents: Lab: 1.!Diffuse!chronic encephalitis!within!both!gray!and!white!matter!with!
1.!Seizures!and!motor!problems.! 1.!Increased!IgG!in!CSF.! glossitis!in!parenchyma!and!inflammation.!
2.!Problems!in!school!and!behavioral!changes.! Prognosis:!
! 1.!Coma!and!death.!
!
Uses:
1.!Diagnose!a!vasculitis!
2.!Differentiate!between:!
1.!Axonal!disease!–!ovoid.!
2.!Demyelinating!disease!–!myelin!with!
different!thickness!on!opposite!sides!of!node.!!!
Viral!encephalitis! Presents: 1.!Herpes!simplex!virus:
1.!Mental!status!change,!fever,!headache,!and!may!progress!to!coma.!
Herpes!simplex!virus:!
1.!Petechial!hemorrhages!in!the!temporal!lobe!(limbic!encephalitis).!
HIV:!
!
1.!Cerebral!involvement!leads!to!AIDS!dementia!complex.! 2.!Rabies:!
2.!Microglial!nodules!and!perivascular!multinucleated!giant!cell.!
3.!Immunosupression!may!lead!to!toxoplasmosis!and/or!CNS!lymphoma.!
Rabies:!
1.!Negri!bodies!in!cytoplasm!of!affected!cells,!usually!hippocampal!and!Purkinje!cells.!
2.!Virus!travels!intra"axonally!from!animal!bite!to!CNS!to!cause!symptoms.!
Progressive!multifocal!!leukoencephalopathy!(PML):!
1.!JC!virus!causes!PML!in!immunocomprimised!(especially!AIDS).! ! !
2.!Astrocytes!acquire!bizarre!nuclei!and!large!shapes.! 3.!PML:!ground!glass"appearance"
3.!Oligodendrocytes!in!active!lesions!contain!viral!intranuclear!inclusions.!
!!
!!

! !
!
Cerebral!abscess! 1.!Hematogenous!dissemination!or!direct!spread! CT/MRI:
1.!Occur!in!patients!who!have!had!infective!endocarditis,! from!contiguous!foci.!!! 1.!Ring"enhancing!lesion.!
cyanotic!heart!disease!(right"to"left!shunt),!or!chronic! 2.!Increased!intracranial!pressure:!headache!
pulmonary!abscess.! vomiting,!and!papilledema.!
2.!Also!wound!infections,!mastoiditis,!paranasal!sinusitis,! Toxoplasmosis:!
acute!otitis,!open!fracture,!previous!neurosurgery.! 1.!Infection!is!result!of!oocyst!ingestion!shed!in!
3.!Are!not!associated!with!prions!and!viruses.! cat!feces.!
2.!Transplacental!infection!of!fetus!with! !
neurologic!consequences!may!occur.! 1.!Each!cyst!is!filled!with!bradyzoites,!and!are!called!tachyzoites!when!
3.!In!AIDS!patients!intracerebral!mass!lesions! present!ouside!the!cyst.!
(central!necrosis!and!chronic!inflammation)!may!
be!present!
Amoebic!abscess:!
1.!Infection!occurs!via!nose!from!fresh!water!or!
from!ingestion.!
2.!Nasal!invasion!results!in!an!acute,!rapidly!
progressive!abscess!and!can!lead!to!death!if!not!
treated.!
3.!Enteric!invasion!is!a!slower!progression.! !
1.!Amoeba!have!a!granular!cytoplasm!with!a!nucleus!with!a!
nucleolus.!

!! !