Download class • assignment • september 8, 1997

PETE KANG • NEW YORK UNIVERSITY SCHOOL OF MEDICINE
435 E. 30TH ST. #1108, NEW YORK, NY 10016 • (212) 683-7055 • (800) 5-SPRINT, PIN#: 3626495 • [email protected]
NEUROPATHOLOGY • TERMS TO KNOW FOR THE TEST • JUNE 27, 2017
The Basics
 coagulative necrosis  liquefactive necrosis 
 Herniations:
cavitation
1) sub-falxian
 Areas sensitive to hypoxia:
2) uncal/transtentorial
1) watershed zone of infarction (“man in a
a) midbrain/peduncle compression
barrel” syndrome), during hypotensive
b) oculomotor nerve compression
ischemic episode
c) posterior cerebral artery compression
2) laminar necrosis
d) Duret hemorrhages
3) Sommer’s sector of hippocampus
e) Kernohan’s notch phenomenon
4) Purkinje cells
3) symmetric bilateral temporal herniation
 Sources of Emboli
4) cerebellar tonsilar
1) cardiac origin: atrial fibrillation, valve
 Circle of Willis
vegetations, mural thrombi at site of MI
 Astrocytes lay down the scar (gliosis), expresses
2) aortic arch & carotid arteries (bifurcation)
GFAP.
3) fat emboli
4) air emboli (iatrogenic, diving)
 Sommer sector of hippocampus is the most
5) paradoxical embolism (pts with cardiac
vulnerable region to hypoxia.
defect)
 Hypereosinophilic neurons are a sign of

Transient
Ischemic Attacks:
hypoxic injury.
1) carotid: motor/sensory deficits or
 Central chromatolysis of neurons is a sign of
monocular blindness
axonal damage.
2)
vertebrobasilar: dizziness, ataxia, diplopia,
 coup and contra-coup contusions
binocular blindness, CN deficits
 epidural hemorrhages  meningeal arteries
 Lacunae are usually due to occlusion of small
 subdural hemorrhages  venous bleeds,
arteries (basal ganglia, internal capsule).
subarachnoid space
 Causes of Intracerebral Hemorrhages:
1) hypertension
Vascular Diseases
2) saccular aneurysm
 CNS arteries have no external elastic lamina.
3) bleeding diathesis
 Causes of Global Cerebral Ischemia:
4) sepsis
1) circulatory arrest
5) tumors
2) hypotension w/wo hypoxia
 Common Sites of Intracerebral Hemorrhages:
3) primary hypoxia
1) basal ganglia/thalamus  putamenal
4) profound hypoglycemia
hemorrhage can disturb posterior limb of
5) carbon monoxide intoxication
internal capsule  hemiparesis
6) cyanide intoxication
2) pons
 Endarterectomy recommended to reduce arterial
3) cerebellum
occlusions.
 Don’t forget about aneurysms.
 Cerebral Ischemia:
 Arterial-Venous Malformations
1) bland (permanent vascular occlusion)
1) in spinal canal  chronic progressive
2) hemorrhagic (restored after ischemia)
paraparesia
Sequence:

Cerebral
Amyloid Angiopathy (see also
0-1.5 days: hypereosinophilia
Alzheimer’s
Disease)  lobar hemorrhages
2 days: karyorrhexis, neutrophils
 Cerebral Autosomal Dominant Arteriopathy
3 days: macrophage
with Subcortical Infarcts & Leukoencephalopathy
5 days: capillary proliferation (contrast
(CADASIL) is associated with notch3 gene
enhancement)
mutation a form of systemic vascular disease
7 days: gliosis
 Know of VEGF, Angiopoietin 1 & 2
1 month: marked gliosis
6 months: status spongiosus
Infections
1
PETE KANG • NEW YORK UNIVERSITY SCHOOL OF MEDICINE
435 E. 30TH ST. #1108, NEW YORK, NY 10016 • (212) 683-7055 • (800) 5-SPRINT, PIN#: 3626495 • [email protected]
 Acute Bacterial Meningitis:
1) 3 LP signs:
a) Increase in Cells (>5/l)
b) Increase in Proteins (>20-50mg/dl)
c) Decrease in Glucose (<40-70mg/dl)
2) common causative organisms (adults):
a) Streptococcus pneumoniae (sporadic)
b) Neisseria meningitidis (epidemic)
i) causes Waterhouse-Friderichsen
syndrome: meningococcemia,
DIC, hemorrhagic infarction of
adrenals, shock, & death
ii) enters via endocytosis
3) majority of the pus is on the convexity
4) people die due to:
a) increase in CSF pressure/herniation
b) secondary ischemic damage
c) damage to arachnoid granulations 
hydrocephalus
d) brain abscess
5) common routes of infection:
a) pneumonia  sepsis  colonization
of CSF
b) sinus infections  dural penetration
 CSF
c) vertebral bones  dural penetration
 CSF
d) hydrocephalus  surgical shunt 
CSF
6) meningitis  vasculitis  thrombosis 
embolization  secondary ischemic
attacks
7) meningitis in children:
a) common causative organisms:
i) E. coli (and other Gram negative
rod organisms)
ii) group B beta (hemolytic) Strep
has early and late patterns of
infection (biphasic)
iii) Klebsiella
iv) Citrobacter
v) Pseudomonas
vi) Listeria monocytogenes
vii) Haemophilus influenzae  otitis
media/pharyngitis (enters via
extracellular penetration of
epithelium)
b) It is common to get cerebritis (as
opposed to the adult version)
2
c) It is common in neonates (vs. adults)
to get thrombosis of superior sagittal
sinus  hemorrhagic venous infarct
d) multicystic encephalomalacia
(MCEM)
i) very fragile parenchyma
ii) multiple cystic spaces/dilated
ventricles
iii) causative organisms:
Citrobacter, Campylobacter,
Klebsiella, E. coli, other Gram
negative rods
8) TB meningitis
a) granulomatous reaction
b) unlike other bacterial meningitis,
largely concentrated @ the base of
the brain, brainstem, basal cistern,
bottom of frontal lobes
c) look like tumor
d) Pott’s Disease is a TB involvement in
the vertebral column (vertebral
osteomyelitis)
 Brain Abscess (Brain Parenchymal Infection)
a) a vessel-damaging event (vasculitis,
meningitis, emboli) must occur so that
organisms can access parenchyma (e.g. a
shower of septic emboli from bacterial
endocarditis)
b) histological features (inout): organisms
& PMNs  mixed infiltrate  chronic
infiltrate  fibrous (from vasculature)
wall
c) mycotic aneurysms caused by septic
emboli
 Spirochetal Infections
a) classical CNS syphilis (Treponema
pallidum) is divided into:
i) meningovascular syphilis (Heubner’s
endarteritis)
ii) gumma syphilis (granulomatous
masses, like TB)
iii) parenchymal disease:: tabes dorsales
& general paresis
iv) congenital syphilis
b) Lyme disease (Borrelia burgdorferi)
causes peripheral neuropathy
 Fungal Infections
a) usually pts are immunocompromised or
are infants
b) Crytococcus neoformans
PETE KANG • NEW YORK UNIVERSITY SCHOOL OF MEDICINE
435 E. 30TH ST. #1108, NEW YORK, NY 10016 • (212) 683-7055 • (800) 5-SPRINT, PIN#: 3626495 • [email protected]
i)
“glistening” sulci due to
polysaccharide capsule of C.
neoformans
ii) weak inflammatory reaction
iii) sometimes granulomatous reaction
iv) localized at the base of the brain
v) do not form pseudohyphae
vi) In AIDS, organism penetrate vessels
and grow perivascularly
vii) flask abscesses
c) Aspergillosis
i) profound inflammatory response
ii) typically attack blood vessels 
vasculitis  hemorrhage 
infarction  much destruction
d) Candidosis
i) causes meningitis & myelitis in
immunocompromised pts.
 Viral Infections
a) CMV:
i) signs: diagnostic CMV inclusions,
perivascular encephalitis, neuronal
phasia
b) Herpes Simplex Virus (HSV):
i) it’s a neurological medical emergency
ii) signs: hemorrhagic CSF,
hemorrhagic & necrotizing
process involving the temporal lobe,
insular cortex, frontal lobe
iii) vascular damage
iv) Cowdry type A inclusions seen
c) HIV
i) ventriculomegaly
ii) giant cell leukoencephalopathy
(abnormal myelin pattern) in a
perivascular pattern
iii) the multinucleated giant cells are
packed with HIV
iv) usually coinfected with CMV
(retinitis, bowel/CNS/PNS
involvement)
 ventriculitis a sign of CMV
ependymitis
 CMV sometimes surrounded by
microglial nodule
 CMV infects Schwann cells
d) poliovirus attacks motor neurons after
proliferation in the
oropharynx/ileum/Peyer’s patches
 Parasitic Infections
a) Neigleria fowleri
i)
causes extensive damage and
hemorrhage in the brain
ii) may look like histiocytes
b) Toxoplasma gondii
i) common in immunocompromised
pts
ii) shows as multiple ring-enhancing
lesions, with predilection for basal
ganglia
 could be B-cell lymphoma
iii) often induces vasculitis  secondary
infarction
c) Taenia solium
i) ring-enhancing lesion in MRI
ii) cysticercosis can degenerate and
induce release of cytokines
iii) causes Jacksonian seizures
iv) Rassimer’s form may implicate
leptomeninges and ventricles
Skeletal Muscle/Peripheral Nerve Disorders
 Neurogenic Diseases
a) amyotrophic lateral sclerosis (ALS, aka
Lou Gehrig’s Disease)
i) characteristic change at the cauda
equina (degeneration of type I fibers)
ii) positive findings: angulated fibers,
fiber type grouping, group atrophy
iii) negative findings: nuclei remain at
periphery, no regenerating fibers
b) Werdnig-Hoffman disease (spinal
muscular atrophy type I) a rapidly
progressive infantile form
c) Kugelberg-Welander disease slower
infantile/juvenile form
 Muscular Dystrophies
a) Duchenne dystrophy
i) most common/most severe; X-linked
ii) pseudohypertrophy fatty
replacement and fibrosis of muscle
iii) “Gower’s sign”
iv) muscle fibers slightly enlarged with
internalized nuclei, fibrosis, lack of
dystrophin, grossly replaced by
adipose tissue
b) Becker dystrophy less severe form
affecting older pts
c) Myotonic dystrophy
i) classic form (can’t let go of your
hands)
3
PETE KANG • NEW YORK UNIVERSITY SCHOOL OF MEDICINE
435 E. 30TH ST. #1108, NEW YORK, NY 10016 • (212) 683-7055 • (800) 5-SPRINT, PIN#: 3626495 • [email protected]
ii) congenital form (associated with
mental retardation, high rate of
neonatal mortality)
iii) gene locus in chromosome 19 (CTG
repeat important)
 Inflammatory Myopathies
a) polymyositis
i) T-cell mediated
ii) degeneration of myofibers and
regeneration after imflammatory
attack
iii) chronic progression to fibrosis and
severe loss of muscle tissue
b) dermatomyositis
i) B-cell mediated
ii) affects blood vessels “tubuloreticular
structures” in endothelial cells 
peripheral myofiber atrophy with
preservation of central myofibers
 Other Diseases
a) sarcoidosis
b) trichinosis
 Metabolic Myopathy
a) periodic paralysis
i) hypokalemic/hyperkalemic forms
ii) typical vacuoles in paralyzed muscle
iii) set off by cold or exercise
iv) muscle cannot propagate an action
potential due to ion change
b) glycogen storage myopathies
i) Pompe’s disease (type II, acid maltase
deficiency) glycogen accumulation
ii) Cori disease (type III, amylo 1-6
glucosidase deficiency) abnormal
polysaccharide accumulation
iii) Type IV (transferase deficiency)
iv) McCardle’s disease (type V,
myophosphorylase deficiency)
v) Type VII (phosphofructokinase
deficiency)
a) mitochondrial myopathy
i) “ragged red fibers” has mitochondria
at periphery of myofibers
ii) EM shows “parking lot inclusions”
d) endocrine disorders with Cushing’s
disease, long term steroid treatment can
cause significant atrophy of type II
myofibers
Neurodegenerative Disorders
 Alzheimer’s Disease
4
a) common sign is perservation
b) general atrophy of neocortical association
areas, medial temporal lobe,
hippocampus, with MI, striatal, auditory,
Hessel’s gyrus largely spared
c) microscopic features:
i) senile plaques
ii) neurofibrillary tangles
 intra-cytoplasmic neuronal
inclusions in hippocampus &
neocortex
 paired helical filaments of
abnormally phosphorylated Tau
protein
iii) congophillic angiopathy
 deposition of amyloid in cerebral
blood vessels
 amyloid beta peptide (sA)
toxic via free radical damage and
stimulation of inflammation
d) two forms:
i) familial early onset
 <60 yrs, autosomal dominant
 presenilin 1 (chromosome 14,
cell membrane protein) & 2
(chromosome 1)
ii) sporadic late onset
 >60yrs
 apoE linkage (apoE4 a risk
factor)
iii) also linked to PP (amyloid
precursor protein) on chromosome
21
e) treatment options
i) cholinergic treatment
ii)  secretase inhibition
 Binswanger’s Disease
a) diffuse demyelination (periventricular)
with some sparing of subcortical white
matter tracts associated with
arteriosclerosis
b) diffuse hyalinosis of vessels  general
hyperperfusion  loss of
oligodendrocytes
 Pick’s Disease
a) localized form of atrophy affection
temporal and frontal lobes
b) Pick’s bodies (neuronal cytoplasmic
round inclusions of abnormally
phosphorylated neurofilament proteins,
etc. & Pick’s cells (ballooned neurons)
PETE KANG • NEW YORK UNIVERSITY SCHOOL OF MEDICINE
435 E. 30TH ST. #1108, NEW YORK, NY 10016 • (212) 683-7055 • (800) 5-SPRINT, PIN#: 3626495 • [email protected]
c) “knife-blade” atrophy or “walnut brains”
d) frontotemporal dementia (a variant)
associated with mutated Tau gene
 Prion Diseases
a) diseases of abnormal protein
conformation
b) Creutzfeldt-Jakob disease (CJD):
i) rapid progression (death in 1 year)
ii) signs:
 spongiform change
 neuropil vacuolation
 gliosis
 scarcity of neurons
c) new-variant CJD is a human form of
bovine spongiform encephalopathy (BSE)
 Parkinson’s Disease
a) rigidity, bradykinesia, resting tremor
b) loss of dopaminergic cells in substantia
nigra compacta
c) Lewy bodies eosinophilic cytoplasmic
neuronal inclusions only found in
idiopathic PD or paralysis agitans
d) familial forms associated with mutations
in alpha-synuclein gene
 Diffuse Lewy Body Disease
a) second leading cause of dementia after
AD
b) Lewy bodies in neurons of SN & cortex
 Huntington’s Chorea
a) autosomal dominant inheritance
chromosome 4 CAG repeat
b) choreoathetosis & dementia
c) severe atrophy of the head of the caudate
Pediatric Neuropathology
 Neural Tube Defects
a) anencephaly
i) failure to close the anterior
neuropore
ii) small head, no calvaria, area
cerebrovasculosa (hemorrhagic
intracranial mass), eyes at top
b) rachischisis failure of anterior
neuropore and then-some to close 
iniencephaly (no neck)
c) encephalocoel outpouching of CNS
tissue of the head
d) myelocoel outpouching of CNS tissue
of the spinal cord
5
e) meningomyelocoel myelocoel with
associated meninges
f) lumbrosacral meningomyelocoel failure
to close posterior neuropore
g) Arnold-Chiari malformation
i) failure to close posterior neuropore
 CSF pressure goes down 
smaller skull  crowding of
posterior fossa  herniation of
cerebellum through foramen
magnum into cervical spinal canal
ii) “S” or “Z” brainstem abnormality
 Neuronal Migration Defects
a) agyra or pachygyra
b) polymicrogyra
c) heterotopic nodule (periventricular),
remnant of unmigrated germinal matrix
tissue
d) tuberous sclerosis
i) associated with TS1 and TS2 genes
ii) nodular masses in focal irregular
fashion
iii) can develop into true neoplasms 
subependymal giant cell astrocytomas
iv) “candle guttering” lesions
v) half-neuronal, half-astrocyte
characteristics (GFAP, synaptin
positive)
 Neural Tube Folding Defects
a) arhinencephaly absence of
rhinenecephalon (olfactory tracts &
related apparatus)
b) holoprosencephaly no midline fissures
or features (one big cortex)
c) Dandy-Walker autopsy no vermis
 Perinatal Brain Damage
a) abnormal closure of the aqueduct
hydroencephalus  hydranencephaly
b) absence of corpus callosum
c) porencephaly usually of the middle
cerebral artery territory
d) perinatal telencephalic
leukoencephalopathy (PTL)
i) degeneration of white matter,
sometimes cystic
ii) gliosis, no oligodendrocytes,
perivascular amphophillic globules
e) germinal matrix hemorrhages usually in
premature babies with weak vessels in
PETE KANG • NEW YORK UNIVERSITY SCHOOL OF MEDICINE
435 E. 30TH ST. #1108, NEW YORK, NY 10016 • (212) 683-7055 • (800) 5-SPRINT, PIN#: 3626495 • [email protected]
germinal matrix areas hemorrhage into
tissues and ventricles  hemocephalus
f) multicystic encephalomalacia infectious
process
 Shaken Baby Syndrome
a) signs:
i) subdural hematomas
ii) cerebral edema
iii) bilateral retinal hemorrhages w/
retinal detachment
iv) w/wo cervical medullary
hemorrhages or cervical spinal
hemorrhages
 Neuronal Storage Disorders
a) Tay-Sachs disease (GM2 gangliosidosis,
hexosaminidase A deficiency caused by
mutation in HEXA gene,  subunit)
b) Hunter’s & Hurler’s syndrome
(mucopolysaccharidoses)
c) Neimann-Pick disease & Gaucher’s
disease (lipid metabolism disorder)
d) Neuronal Ceroid Lipofuscinosis
i) progressive mental retardation and
seizures, choreoathetotic movements,
blindness
ii) lipofuscin accumulation in neurons
iii) marked neuronal lose and gliosis
Demyelinating Diseases
 Multiple Sclerosis
a) periventricular brown-colored, firm
lesions
b) geographically associated with: North
America, Europe, Australia, & South
Africa
c) more females than males; more white
than black; age of onset 20-50yo
d) signs:
i) neurological signs (optic neuritis)
ii) multiple periventricular white matter
lesions seen in MRI (can also affect
gray matter)
iii) classic course of attack and remission
 Devic’s Disease
a) acute, extensive necrosis of spinal cord
with demyelination, often with
involvement of optic system
b) MRI shows enhancing mass in cervical
spinal cord
6
 Differential Diagnosis of Ring-Enhancing
Lesions it can be:
a) cerebral abscess
b) cerebral metastasis
c) lymphoma
d) toxoplasmosis
e) demyelination
 Histological Characteristics of Demyelination
a) many histiocytes (HM56 marker)
b) reactive astrocytes
c) shadow plaque intermediate zones of
myelin “loss” are actually areas of
remyelination
 Balo Concentric Sclerosis zebra-like pattern
 Adrenoleukodystrophy
a) enzymatic deficiency  abnormal
metabolic accumulation of long fatty
acids (curvilinear lamellae?)
b) myelin loss with axonal preservation
 Acute Demyelinating Syndromes
a) post-vaccination to mumps & measles
 Acute Disseminated Encephalomyelitis
a) post-infection or post-vaccination
b) cerebral edema, perivenous loss of
myelin, perivascular inflammation
 Acute Necrotizing Hemorrhagic
Leukoencephalitis
a) hemorrhagic form of post-infectious
demyelinating disorder
 Central Pontine Myelinolysis (CPM)
a) iatrogenic condition trying to correct
hyponatremia too quickly
 Marchiafava-Bignami Disease (MBD)
a) demyelination of corpus callosum &
anterior commissure (drinkers of crude
red wine)
 Progressive Multifocal Leukoencephalopathy
a) AIDS related
b) non-enhancing lesion
c) bizarre astrocytic cells with hypertrophic
and hyperchromatic nuclei
d) JC virus damages oligodendrocytes and
transforms astrocytes
e) oligodendrocytes have viral inclusions