Inflammatory, Ischemic, Toxic Flashcards
what are the 4 types of classical/charcot MS?
- relapsing remitting
- secondary progressive
- primary progressive
- relapsing progressive
what are the 2 rare rapidly progressive forms of MS?
- Acute/Marburg type
- concentric sclerosis (Balo’s dz)
MS plaques can have CD4 predom or CD8 predom lesions. When do those each happen?
CD4 predom: active plaques
CD8 predom: less active
Do normal CNS cells express MHC II ags?
nope
but it can happen in several inflammatory disorders, including MS
what are shadow plaques?
they have reduced but not absent myelin staining (usually demyelinated and remyelinated)
what is solochrome cyanin?
stains myelin
Inactive plaques are hypocellular; when you DO see cells, what are they?
astrocytes
they lose oligos
What is the characteristic histo feature of Balo’s?
plaques comprised of alternating concentric rings of demyelinated and myelinated white matter
T/F: you only see the Balo finding in Balo’s
false; you can see plaques with bands or islands of preserved myelin in classic MS
4 grades of subependymal/germinal matrix hge
- germinal matrix only
- extend into lateral ventricle
- expand lateral ventricle
- extend into adjacent brain parenchyma
Most (60%) of supendymal/germinal matrix hge happens when?
within 48h of birth
(anywhere from 6h to 8d postpartum)
what population of neonates get cerebellar hemorrhages?
low birth weight preemies
5 micro findings of telencephalic leukoencephalopathy
- hypocellular WM
- no myelination glia
- diffuse gliosis
- karyorrhectic glial nuclei
- amphophilic globules
what is unique about purkinje cells and hypoxic injury in babies before 37w gestation?
they are LESS vulnerable to hypoxic injury than the internal granular layer cells
what ischemic spinal cord damage happens in preemies?
infarction in central lumbosacral cord segments
what ischemic spinal cord damage happens in term neonates?
diffuse necrosis affecting ventromedial neurons
what is a pattern of “selective vulnerability to hypoxia in neonates” in the cerebellum?
necrosis of DEEP cerebellar cortex with sparing of the superficial parts of the folia
what happens after a small germinal matrix bleed happens? like how does it resolve/manifest
periventricular cysts
aka
subependymal matrix cysts
they have tiny little projections into the cyst, which are residua of matrix tissue
what are the 2 manifestations of post-white matter necrosis d/t birth injury?
- sclerotic atrophy (centrum semiovale)
- cysts traversed by gliomesodermal bands (corners of LVs)
what are the post-grey matter necrosis findings?
- ulegyria (mushroom)
- cortical marbling (irregular myelination/etat fibromyelinique)
what is status marmoratus?
after pre or postnatal hypoxia but before myelination (so before 6mo)
gliotic/cystic BG/thalamus lesions (chronic) with hypermyelination + gliosis
marbled parenchyma, corrugated surface
gross findings of crossed cerebellar atrophy
unilateral cerebral hemisphere injury (chronic)
ipsilateral atrophy of basis pontis
contralateral atrophy of cerebellum
what kind of bilirubin do you have in kernicterus?
unconjugated
what are the characteristically affected structures in kernicterus?
- subthalamic nucleus
- globus pallidus
- lateral thalamus
(less common: CA2, LGN, colliculi, SN, pars reticularis, brainstem reticular formation, cranial nerve nuclei, Purkinjes, dentate & olivary nuclei)
2 characteristic things of neuromyelitis optica
- optic neuritis
- acute transverse myelitis
(within weeks of each other)
what are the 3 supportive criteria for neuromyelitis optica that you need 2 of?
- contiguous spinal cord MRI lesion over 3+ vertebral segments
- brain MRI NOT dx of MS
- NMO-Ig seropositive (serum has aquaporin 4 antibodies)
what are 2 AQP4-rich regions in the brain?
hypothalamus
periaqueductal region
(you can see demyelinating lesions here [or elsewhere])
what inflammatory cells dominate in neuromyelitis optica?
neutrophils
eosinophils
in neuromyelitis optica, what do you lose WITH AQP4?
EAAT2 (Na+ dependent excitatory amino acid transporter 2)
what does the spinal cord look like in resolved neuromyelitis optica?
brown discoloration
what usually precedes ADEM?
systemic viral infxn or vaccination
or nothing!
most common preceding etiologies of ADEM
infxn: (tbh, think of vaccines, even tho it’s not) MMR, VZV, flu, and mono/EBV
vax: smallpox, rabies
characteristic ADEM micro
periVENULAR inflammation (NOT around arteries) with a (tight!) zone of demyelination
difference in clinical prognosis between ADEM and AHL
ADEM is usually recoverable
AHL is usually fatal within days
gross appearance of brain in ADEM
congested WM BVs surr by ill-defined gray discoloration (that’ll be the demyelination zone)
Mottled CC
AHL gross appearance
perivascular WM hge (petechial and some coalescent) and associated gray-brown d/c
involvement of brainstem & cerebellum
micro findings of AHL
Ring- and ball-shaped perivascular hges
BVs > fibrinoid necrosis > zone of necrotic tissue w/ debris > larger zone of hge
(they also get perivascular demyelination like in ADEM)
what are most cases of trigeminal neuralgia caused by?
compression of trigeminal nerve root by an aberrant loop of artery or vein + de/remyelination
what is specifically implicated in the psychosis of Wernicke-Korsakoff?
medial dorsal (or medial thalamic) nuclei
besides the mammillary bodies, where ELSE can you see wernicke’s?
hypothalamus
medial thalamic nuclei
floor of 3rd ventricle
periaqueductal region
colliculi
pontomedullary tegmental nuclei (esp dorsal motor nucleus of vagus)
inferior olives
cerebral cortex (oh good)
how does a wernicke lesion typically look microscopically?
edema
PRESERVED neurons
loss of intervening tissue
loss of myelinated fibers
(makes the capillaries seem really prominent)
what causes pellagra?
nicotinic acid deficiency
OR
tryptophan deficiency
micro finding in pellagra
striking chromatolysis of Betz cells and pontine/cerebellar dentate neurons
what is the clinical triad of pellagra?
- dermatitis
- diarrhea
- dementia
what setting is most likely to be the culprit in vitamin B6 deficiency?
pts receiving isoniazid (or other pyridoxine antagonists)
what is the other name for vitamin B6?
pyridoxine
why do pyridoxine deficiency and pellagra have some syndrome overlap?
pyridoxine deficiency impairs the synthesis of niacin from tryptophan
pellagra is tryptophan deficiency
how does pyridoxine deficiency cause seizures?
Vitamin B6 is involved in GABA synthesis
no B6 = no GABA = seizures
what does the spinal cord look like in severe vitamin B12 deficiency?
mildly shrunken
discolored posterior & lateral columns (esp in lower cervical & thoracic regions)
what’s the other name for vitamin B12
cobalamin
What does vitamin B12 deficiency look like microscopically?
symmetric spongy vacuolation & myelin degen
THORACIC cord
first in post columns, then corticospinal/spinocerebellar tracts in lateral columns
what causes subacute combined degeneration?
vitamin B12/cobalamin deficiency
what is the usual cause of vitamin B12 deficiency?
autoimmune atrophic gastritis
what is the earliest histologic abnormality in subacute combined degeneration?
vacuolation within myelin sheaths in posterior columns
what’s the other name for vitamin E?
alpha-tocopherol
why does alpha-tocopherol absorption require biliary, pancreatic, and small intestine function?
because it’s fat-soluble
what vitamin deficiency causes acanthocytosis?
vitamin E/alpha-tocopherol
micro finding of vitamin E deficiency
axonal swellings, esp distal parts of longer axons
most prominent in gracile & cuneate fasciculi
neuronal loss of DRG
what are the most susceptible neurons to hypoglycemia?
cortex (layers 3, 5, & 6)
caudate
putamen
CA1
Dentate nucleus in INFANTS
What is the MAJOR difference in histo btwn hypoxic-ischemic and hypoglycemic injury?
PURKINJES ARE SPARED in hypoglycemia!!!
gross findings of long-term survivors of hypoglycemia
granular & atrophic neocortex
hippo & tail of caudate atrophy
irregular shrinkage of caudate, causing bumpy ventricular surfaces
what 2 structures are usually SPARED in long-term survivors of hypoglycemia?
cerebellar cortex (incl Purkinjes)
&
globus pallidus
what are the general micro features of long-term survivors of hypoglycemia?
- cortical laminar neuronal loss (layers 3, 5, 6)
- gliosis & capillary proliferation, esp in hippo/subic/dentate
- WM rarefaction & gliosis
what does hyperthermia look like on microscopy?
just like acute hypoxic-ischemic injury, including affecting Purkinjes
what is osmotic demyelination syndrome?
central pontine myelinolysis
which can also manifest as extrapontine demyelination fwiw
gross appearance of central pontine myelinolysis
basis pontis has soft, granular fusiform gray discoloration which can be v asymmetric
where is central pontine myelinolysis most noticeable usually (lesion has the largest area)?
upper pons
central pontine myelinolysis usually spares what?
myelin in a narrow rim of subpial tissue (of basis pontis)
what are the extrapontine areas that can get osmotic demyelination syndrome?
cerebellum
LGN
capsula externa or extrema
subcortical WM
BG
Thalamus
internal capsule
how can you tell (nonpontine) osmotic demyelination syndrome from an active MS plaque?
distribution
age of lesions (they’ll all be the same age in ODS)
ODS will have less lymphocytes
what are the other 2 names for Fahr’s disease?
Familial idiopathic calcifications of the BG
&
striopallidodentate calcinosis
what’s the difference between Fahr’s disease & calcs in primary hypoparathyroidism?
calcs are usually more diffuse in hypoparathyroidism
T/F: the mineralized vessels in Fahr’s disease are made up of only calcium
FALSE
Ca AND
iron, magnesium, aluminum, & glycoproteins
what’s the underlying issue in posterior reversible encephalopathy syndrome (PRES)?
hypercalcemia
what is affected in PRES?
predominantly posterior white matter, subcortical (& overlying cortical) lesions (edema)
SYMMETRIC
PRES is usually a/w what very common issue in adults?
hypertension
what are the micro findings of hypertension &/or PRES?
microvascular necrosis
perivascular exudates
microhemorrhages
edema
when do you see Alzheimer type II astrocytes?
acquired hepatic encephalopathy
OR!
uremia (non-hepatic metabolic encephalopathies)
OR!
Wilson’s disease!
what is the technical description of alz type II astrocytes?
enlarged vesicular nucleus with marginated chromatin
scanty cytoplasm
little or no GFAP
where are the alz type II astrocytes weirdly lobulated?
pallidum
subthalamus
dentate nucleus
brainstem
what 3 sequelae are found in chronic/recurrent hepatic encephalopathy?
- patchy pseudolaminar necrosis/microcavitation @ depths of sulci @ G-W jxn
- dorsal pole of putamen neuronal loss/gliosis/microcavitation
- degeneration of corticospinal tract fibers (chronic hepatic myelopathy)
what are Opalski cells?
altered astrocytes with small hyperchromatic nucleus & finely granular deeply eosinophilic cytoplasm
(central nucleus does not seem to be reliable)
what disease are Opalski cells a/w?
WILSON’S DZ (esp in GP)
and
hepatic encephalopathy
gross lesions of Wilson’s disease
brown, shrunken caudate and putamen
especially middle third of putamen
centrally cavitated putamen
what does the micro of the putamen look like in Wilson’s disease?
neuron loss
lipid & pigment laden macs
fibrillary astrocytes
Alz type II astrocytes
most common neuro abnormality in celiac disease
cerebellar atrophy
> loss of Purkinjes
> variable loss of granule cells
> Bergmann gliosis
what’s the underlying cause of dialysis dementia?
aluminum toxicity
what’s the underlying cause of dialysis dysequilibrium syndrome?
cerebral water intoxication d/t hypo-osmolality
is dialysis dysequilibrium syndrome more frequently due hemo or peritoneal dialysis?
hemodialysis
what happens to axons in multifocal necrotizing leukoencephalopathy?
Swollen axons in areas of necrosis
then the swollen axons calcify (hematoxyphilic)
what is the toxic element in dialysis encephalopathy syndrome?
aluminum
what is the histo finding in dialysis encephalopathy syndrome?
argyrophilic material (containing aluminum) in choroid plexus & brainstem nuclei
what does chronic arsenic intoxication cause and how?
peripheral axonal neuropathy
mechanism: binds sulfhydryl groups > inhibit cellular respiration
what pathology do you see in chronic arsenic intoxication?
chromatolysis + loss of anterior horn cells
THAT’S WHAT YOU SEE IN POLIO!!!!!
what is the treatment for trypanosomiasis and what can it cause accidentally
Melarsoprol
can cause AHL
what kind of clinical syndrome does Bismuth xs cause?
CJD-like
anxiety, depression, insomnia, myoclonus, gait issues
what can lead poisoning look like in the CNS?
- edema/hydrocephalus
- endothelial swelling, petechial hge, capillary necrosis, thrombosis
- perivascular PAS+ globules
how does manganese toxicity work? (mechanism)
astrocytic mitochondria take it up, then they can’t undergo oxidative phosphorylation
what is the pathology of manganese toxicity?
gliosis & neuron loss in BG
but NOT substantia nigra
the clinical presentation of manganese looks like WHAT? and how can you tell them apart?
looks like parkinson’s
manganese will have preserved SN
what does in-utero mercury exposure affect most severely?
cerebellum degen
(and cortical spongiform degen)
what 2 structures does thallium affect?
motor neurons (chromatolysis)
and
posterior columns
how does triethyl tin manifest clinically and histo?
Clin: increased ICP and flaccid paraparesis
Histo: WM edema 2/2 vacuoles in myelin
How does triMethyl tin manifest clinically and histo?
clin: confusion, confab, amnesia
histo: CA3 neurons apoptosis, BG, amygdala
acrylamide causes a distal degen of long axons in the CNS. what do the axonal swellings contain?
neurofilaments
which toxin results in increased atherosclerosis?
carbon disulfide
(cellophane, rayon, viscose, adhesives)
what are the crystals in ethylene glycol poisoning?
calcium oxalate
what are the toxins a/w pain/varnish/glue solvents?
hexacarbons (distal axonopathy)
N-hexane and
Methyl N-butyl ketone
and
toluene (cerebellar atrophy)
why is Methanol toxic?
formaldehyde/formic acid formation in the liver
how does methanol cause blindness?
degeneration of retinal ganglion cells > optic nerve atrophy + gliosis
besides vision, what else does methanol affect?
PUTAMEN
symmetric petechial hges/hgic infarcts in putamina!
toxic oil syndrome & eosinophilia/myalgia syndrome are prob 2 manifestations of ingestion of what?
aniline derivatives
what is the clinical for toxic oil syndrome/eosinophilia-myalgia syndrome
BIPHASIC
1. acute: systemic hypereosinophilia + HA, rash
- 3-6w: paresthesias, myalgias, weight loss, memory/cognition
pathology of toxic oil syndrome/eosinophilia-myalgia syndrome
inflammatory vasculitis in PNS and skeletal muscle
also distal axonopathy with neurofilament accumulation
toxin that results in cranial nerve AND peripheral nerve neuropathies
trichlorethylene (dry cleaning)
5 toxic causes of bilateral BG necrosis
- CO
- cyanide
- methanol
- marchiafava-bignami (chronic alcohol)
- heroin (or other global cerebral hypoxia)
3 metabolic causes of bilateral BG necrosis
- Leigh’s disease
- Infantile holotopisstic/bilateral striatal necrosis (duh)
- Wilson’s disease
mechanism of CHRONIC nitrous oxide exposure
inactivates cobalamin > inhibits methionine synthase > SACD 2/2 cobalamin deficiency
2 things to a/w amphotericin B tox
- parkinsonism
- multifocal necrotizing leukoencephalopathy
what syndrome does clioquinol result in?
subacute myelo-optic neuropathy
what is the overlap between clioquinol tox and rabies?
nodules of Nageotte (degen of DRG cells, proliferation of satellite cells which make little clusters)
complication of L-asparaginase treatment
small cortical hgic infarcts 2/2 superior sagittal thrombosis
histo of chasing the dragon
leukoencephalopathy with sparing of U-fibers
how does botox work
inhibits ACh release at NMJ
how does tetanus work
toxin (C. tetani) enters at NMJ then travels up axon (retrograde) and blocks release of GABA and glycine from spinal inhibitory interneurons
(no inhib = spasms/rigidity)
