Neuro Pathology Flashcards
anencephaly
failure of closure of the rostral neuropore
absence of skull and brain
frog-like appearance
absence of CNS controlled swallowing > maternal polyhydraminos
spina bifida
failure of closure of the caudal neuropore
vertebral defect
spind bifida occulta
no herniation
tuft of hair
meningocele
herniation of the meninges
meningomyelocele
herniation of meninges and spinal cord
cerebral aqueduct stenosis
increased ICP
enlarged head circumference due to dilation of the ventricles
Dandy-Walker Malformation
congenital failure of cerebellar vermis to develop
massively dilated 4th ventricle with absent cerebellum; accompanied by hydrocephalus
Arnold-Chiari Malformation
Type 1
Congenital extension of the cerebellar tonsils through foramen magnum
obstruction of CSF -> meningomyelocele or syringomyelia
presentation @ adolescence or young adulthood
Arnold-Chiari Malformation
Type 2
More rare; 12% die within first year
death result of compression of cranial nerves -> respiratory compromise
syringomyelia
cyst forms within the spinal cord (syrinx)
usually C8-T1
1) effects anterolateral spinothalamic tract; knocks out anterior commissure
CAPE-LIKE distribution
spares DCML
2) expansion -> knocks out ventral horn (LMN) -> flaccid
3) expansion -> knocks out lateral (iml) horn -> sympathetics lost to face (hypothalamic spinal tract)
Poliomyelitis
fecal-oral transmission
oropharynx > small bowel > blood > CNS
damage to ventral motor horn
FLACCID paralysis
Werdnig-Hoffman Disease
Inherited degeneration of ventral motor horn
autosomal recessive
FLOPPY BABY
death occurs within a few years after birth
ALS
degenerative disorder of UMN + LMN
- > flaccid paralysis
- > muscle atrophy
- > fasciculations
- > weakness
- > decreased tone
- > impaired reflexes
- > neg. Babinski
ALS vs. Syringomyelia
ALS spares pain and temp. sensation
How does one get ALS?
- sporadic
2. familial mutation ex. zinc-copper superoxide dismutase causing free radical injury
Fredreich Ataxia
degenerative disorder of the cerebellar and spinal cord
progressive limb and gait ataxia, dysarthria, loss of proprioception and vibration sense
AUTOSOMAL RECESSIVE
expansion of unstable trinucleotide repeat (GAA) frataxin gene chromosome 9
iron buildup with free radical damage
presents early childhood (8-15yrs)
assoc. hypertrophic cardiomyopathy
types of meningitis
bacterial (septic)
viral (aseptic)
fungal
most common sources of meningitis in newborns
GBS (test in 3rd trimester of pregnant women)
E. coli
L. monocytogenes
most common source of meningitis in children/teenagers
N. meningitidis
most common source of meningitis in adults
S. pneumo
most common source of meningitis in old people
L. monocytogenes
most common source of meningitis in non vaccinated infants
H. influenza
most common viral source of meningitis
Coxsackievirus
most common source of meningitis in immunocompromised
fungal
meningitis presentation
headache nuchal rigidity fever photophobia vomiting altered mental status (may be present)
test for meningitis
LP for CSF profile
Bacterial meningitis ( findings)
high PMNs
low glucose
Viral meningitis
LP findings
high lymphocytes
normal glucose
Fungal meningitis
LP findings
high lymphocytes
low glucose
complications of bacterial meningitis
massive amts of exudate and pus
cerebral edema > herniation > death
massive tissue damage > fibrosis > hydrocephalus, hearing loss, seizures
Cerebrovascular Disease (basics)
Neurologic deficits due to CV compromise
1) ischemia (85%)
2) hemorrhage (15%)
Hemorrhagic CVD
intracerebral and subarachnoid
Etiologies of Global Ischemia (CVD)
- low perfusion (e.g. atherosclerosis)
- acute disease in blood flow (e.g. cardiogenic shock)
- chronic hypoxia (e..g anemia)
- repeated episode of hypoglycemia (e.g. insulinoma)
mild global ischemic CVD
transient confusion
moderate global ischemic CVD
infarct in “watershed” areas (areas supplied by end of a circulation)
- pyramidal neurons of the cerebral cortex (layers 3, 5, 6) leads to laminar necrosis
- pyramidal neurons of the hippocampus (temporal lobe)-impt long term memory
- purkinje layer of the cerebellum-integrates sensory perception with motor control
severe global ischemic CVD
diffuse necrosis of the brain > death or vegetative state
ischemic CVD
focal or global
TIA
focal neurologic deficits
symptoms < 24hours
ischemic stroke
focal neurologic deficits > 24hours
ischemic stroke subtypes
- thrombotic
- embolic
- lacunar
thrombotic stroke
due to rupture of atherosclerotic plaque
usually develops at branch points
-> pale infarction; cannot lyse thrombus; cannot get blood to region
embolic stroke
due to thromboemboli
most common site is the left side of the heart (a.fib)
-> red infarct; hemorrhagic infarction; can easily be lysed
lacunar stroke
risk factors: HTN, diabetes, smoking, advanced age
-> lake-like areas of infarct
thickened wall + narrowed lumen > decreased blood going through small vessels
intracerebral hemorrhage
bleeding into brain parenchyma
classically due to rupture of Charcot-Bouchard microaneurysms
basal ganglia is the MOST COMMON SITE
subarachnoid hemorrhage
bleeding into the subarachnoid space
- sudden headache
- “worst headache of my life”
- nuchal rigidity
most commonly (85%) due to berry aneurysm rupture
lack of media layer at the branch point, weak wall, saccular outpouching
assoc. w/ Marfan syndrome, Ehlers-Danlos syndrome, and autosomal dominant polycystic kidney disease
epidural hematoma
lens-shaped lesion
classically rupture of middle meningeal artery (high pressure circuit)
“talk and die”
lucid interval precede neuro symptoms
subdural hematoma
crescent-shaped lesion
tearing of bridging veins
progressive neuro signs
tonsillar herniation
cerebellar tonsils into foramen magnum
compression of brainstem (medulla) -> coma, cardiopulmonary arrest, death
subfalcine herniation
displacement of cingulate gyrus under the falx cerebri
most common type of brain herniation
compression of ACA > infarction
clinical presentation: headache, contralateral leg weakness
uncal herniation
displacement of the temporal lobe uncus under the tentoriumcerebelli
- compression of CN III
down and out
dilated pupil
ptosis - compression PCA -> infarction of occipital lobe (contralateral homonymous hemianopsia)
- rupture of paramedian artery -> brainstem hemorrhage (duret)
oligodendrocytes
myelinate CNS
multiple
schwann cells
myeline PNS
one-to-one
Inherited Leukodystrophies
- metachromatic leukodystrophy
- krabbe disease
- adrenoleukodystrophy
metachromatic leukodystrophy
deficiency of arylsulfatase
- > myelin cannot be degraded
- > accumulates in the lysosome
MOST COMMON
AUTOSOMAL RECESSIVE
krabbe disease
deficiency of galactocerebroside
-> build up of unmetabolized lipids
AUTOSOMAL RECESSIVE
most common in infants
adrenoleukodystrophy
impaired addition of coenzyme A to long-chain fatty acids
X-linked defect
Multiple Sclerosis (MS)
autoimmune destruction of CNS myelin and oligodendrocytes
young adults (20-30) women
relapsing-remitting
MS presentation
- blurred vision in one eye (optic nerve)
- vertigo and scanning speech
- iNO (MLF damage)
- hemiparesis or unilateral loss of sensation
- lower extremity loss of sensation and weakness
- bowel, bladder, and sexual dysfunction (ANS)
How is MS diagnosis made?
MRI: plaques
LP: increased lymphocytes, increased immunoglobulins with oligoclonal IgG bands, myelin basic protein
MS treatment
acute attacks: high-dose steroids
long-term: INF-beta (slows progression)
subacute sclerosing panencephalitis
progressive, debilitating encephalitis
persistent infection of the brain by measles virus
viral inclusions within neurons (gray matter) and oligodendrocytes (white matter)
progressive multifocal leukoencephalopathy
rapid progressive neuro signs leading to death
- visual loss
- weakness
- dementia
immunosuppression leads to reactivation of the latent virus
JC virus
central pontine myelinolysis
focal demyelination of the pons -> “locked-in” syndrome (acute bilateral paralysis)
due to rapid intravenous correction of hyponatremia
predisposed patients: malnourished, alcoholics, liver disease
dementia
degeneration of the cortex
memory + cognitive dysfunction w/o loss of consciousness
movement disorders
degeneration of the brainstem and basal ganglia
Alzheimer Disease
most common cause of dementia
presentation
- slow onset memory loss
- progressive disorientation
- loss of learned motor skills and language
- changes in behavior and personality
- patients become mute and bedridden
- > APP cleaved to A-beta amyloid (as opposed to A-alpha)
- > A-beta amyloid cannot be broken down
- > deposits in the brain
Early-onset AD
familial cases w/ presilin 1 and 2 down syndrome (APP found on chromosome 21)
Allele Assoc. Risk with AD
increased (epsilon 4 allele of apolipoprotein E)
decreased (epsilon 2 allele of apolipoprotein E)
AD Morphology
- Cerebral atrophy with narrowing gyri; sulci widening
- Neuritic plaques
- Neurofibillary tangles (intracellular aggregates of fibers composed of hyperphosphylated tau)
- Loss of cholinergic neurons in the nucleus basalis of Meynert
Vascular Dementia
2nd most common cause of dementia
multifocal infarction and injury due to atherosclerosis or vasculitis
Pick Disease
degenerative disease of the frontal and temporal cortex and spares the parietal and occipital lobes
round aggregates of tau protein (pick bodies) in the neurons of the cortex
behavior and language symptoms (first)
dementia (eventually)
Parkinson’s Disease
Degenerative loss of dopaminergic neurons in the substantia nigra of the basal ganglia
TRAP Tremor Rigidity Akinesia/Bradykinesia Postural instability and shuffling gait
MPTP can cause PD
PD Histology
Loss of pigmented neurons in the substantia nigra and round, eosinophilic inclusions of alpha-synuclein (Lewy bodies)
Huntington Disease
Degeneration of GABAergic neurons in the caudate nucleus of the basal ganglia
AUTOSOMAL DOMINANT
Expanded CAG repeats
chorea that can progress to dementia and depression
avg age onset 40
chorea
random movement of muscle loss of inhibitory hold on the cortex
anticipation
early onset with early generation
expansion of repeats
occurs during spermatogenesis
akathisia
motor restlessness (an inability to sit still)
athetosis
slow, writhing movements which may resemble dystonia
ballism
proximal, large-amplitude chorea
unilateral=hemiballism
chorea
non-rhythmic unpredictable movements; involuntary, randomly flowing jerks
dystonia
an abnormal posture; the result of co-contraction of agonist and antagonist muscle contractions may also result in twisting repetitive movements
myoclonus
shock-like movements due either to muscle contraction (+) or abrupt loss of muscle tone (-)
sterotypy
a set of movements that last for a time; purposeless repetition of the motor set
tic
patterned simple or complex paroxysmal movements (“sensory tic”)
tremor
rhythmic movement, with amplitude and frequency as in a sine wave, involving one or more body parts
akinesia
lack of purposeful movement
bradykinesia
slowness of movement
normal pressure hydrocephalus
wacky
wet
wobbly
spongiform encephalopathy
degenerative disease due to prion protein PrPc (normal; alpha-helical) PrPSc (pathologic; beta-helical) conversion 1. sporadic 2. inherited 3. transmitted
damage to neurons and glial cells -> intracellular vacuoles
MOST COMMON = Creutzfeldt-Jakob Disease (CJD)
Creutzfeldt-Jakob Disease
sporadic
exposure to prion-infected human tissue (ex. hGH or corneal transplant)
rapidly progressive dementia assoc. with ataxia and startle myoclonus
death < 1 year
CNS tumors
- > metastatic (50%)-commonly from lung, brain and kidney
- > primary (50%)
- > adults above tentorium
- > kids below tentorium
Primary tumor cell types
- astrocytes
- oligodendrocytes
- ependymal cells
- meningothelial cells
- neuroectoderm
Astrocyte Primary Tumors
Polycytic Astrocytoma (children) Glioblastoma Multiforme (adults)
Polycytic Astrocytoma
benign tumor of astrocytes
most common in children
cystic lesion with mural nodule
Glioblastoma Multiforme
malignant high-grade tumor of astrocytes most primary malignant tumor in adults arises in cerebral hemisphere crosses corpus callosum "butterfly" lesions pseudopalisading GFAP + poor prognosis
Oligodendroglioma
malignant tumor of oligodendrocytes
pseudopalisading
region of necrosis surrounded by tumor cells
ependymoma
children
malignant tumor of ependymal cells
most commonly arises in 4th ventricle
perivascular pseudorosettes
meningioma
most common benign tumor in adults
more common in women
round mass attached to dura
tumor expresses estrogen receptor
schwannoma
benign tumor of Schwann cells
commonly involves CN VIII -> hearing and tinnitus
medulloblastoma
malignant tumor derived from the granular cells of the cerebellum (neuroectoderm)
children
drop metastasis to cauda equina
histology > small, round blue cells
craniopharyngioma
- > tumor that arises from epithelial remnants of Rathke’s pouch
- > supratentorial mass in a child/young adult
- > calcifications on imaging
may compromise optic chiasm > BITEMPORAL HEMIANOPSIA
don’t confuse with pituitary tumor
amyotrophy
describes clinically evident muscle atrophy
lateral sclerosis
describes the gross pathology findings of sclerosis of the lateral CST in the spinal cord
sclerosis
scarring
dysmetria
abnormal measure; finger-nose-finger
dysdiadochokinesia
abnormal rapid alternating movements
past-pointing
overshoot; mirroring
dysarthria
scanning speech; impaired articulation and prosody (rhythm)
encephalocele
brain herniates through a defect in the skull bones
most common site occipital bone
metastatic CNS tumor
most common type of CNS tumor
indication: located at the junction of cortical gray and white matter, round shape
tend to metastasize from lung, breast, kidney, colorectal cancer, melanoma
parinaud syndrome
lesion of the dorsal tectum of the midbrain (eg pineal gland tumor) that compresses
- superior colliculus
- pretectal area
- and cerebral aqueduct (obstructive hydrocephalus)
interrupts melatonin production -> disrupts circadian rhythm -> insomnia
palsy of upward gaze
dissociation of light and accommodation
failure of convergence
allodynia
pain from a stimulus that does not normally evoke pain
hyperalgesia
exaggerated response to a normally painful stimulus (e.g. hot shower after sunburn)
taxonomy of pain
nociceptive
inflammatory
neuropathic
dysfunctional
nociceptive pain
no pathology
requires an ongoing noxious stimulus
a high threshold protective alarm system
inflammatory pain
tissue injury with inflammation
allodynia, hyperalgesia, spontaneous pain
a low threshold protective system that promotes healing/repair
neuropathic pain
PNS or CNS lesions
allodynia, hyperalgesia, spontaneous pain, negative symptoms
low threshold-pathologic/maladaptive
dysfunctional pain
altered CNS function–no known lesion/no peripheral pathology
allodynia, hyperalgesia, spontaneous pain, no negative symptoms
low threshold-pathological and maladaptive
resting state (pain)
nociceptive
sensitized (pain)
inflammatory
neuropathic
dysfunctional
physiological pain
nociceptive
inflammatory
pathologic pain
neuropathic
dysfunctional
adaptation
with maintained stimuli, response declines, so cells report stimulus change
receptive field
receptor cells report stimuli in one area (space, orientation, color, frequency, odor etc)
Synucleinopathies (Lewy Body Diseases)
Parkinson's Disease Multiple Systems Atrophy Dementia with Lewy Bodies Essential tremor (occasional) Neurodegeneration with brain iron accumulation (occasional)
Multiple System Atrophy (MSA)
progressive neurodegenerative disorder affecting autonomic nerves and can affect the basal ganglia–orthostatic hypotension (differentiates from PD)
lewy bodies present in oligodendrocytes
Lewy Bodies
cytoplasmic inclusion containing alpha-synuclein, poly-ubiquitin, neurofilament and other proteins
relationship to pathogenesis unclear
