7. Neuropathology Flashcards
The CNS contains four types of supportive neuroglial cell (glia), which are nonconducting cells located close to neurons • Astrocytes • Oligodendrocytes • Microglia • Ependymal cells
Starting with astrocytes:
• Star-like glial cells (glial cells are a general term for resident cells in the CNS)
• Cytoplasm contains: ____ (glial fibrillary acidic protein or GFAP) - used for
pathology when doing histo stains
Oligodendrocytes
• Myelinating cells of the ____ (Schwann is PNS)
Microglia
• small, elongated throughout CNS
• Inconspicuous, gray + white matter
• ____ surveillance
Ependymal Cells
• single ____ cells that line the ventricles + choroid plexus
• form specialized epithelium
intermediate filaments
CNS
immune
cuboidal
Astrocytes foot processes surround brain capillaries and control the exchange of chemicals
• Cytokines
• Homeostasis
• Gliosis (reactive astrocytes)
• Astrocytes participate in inflammatory + degenerative processes
• secrete ____ - common in CNS diseases w/ inflammatory components
i.e. MS
- take up ____ that’s released during neuronal activity
- maintains homeostasis in the CNS
◦ also take up + recycle ____ (I.e. glutamate) + can also produce
NT’s
• When neurons are lost or damaged, they proliferate + become reactive - try to
restore the ____ - ____
◦ so in the pic w/ the red arrow above, he’s saying when you see the cytoplasm this ____, it’s indicative of pathology
• Long standing reactive astrocytes can develop an eosinophilic, proteinaceous deposits called____
cytokines potassium neurotransmitters BBB gliosis visible rosenthal fibers
Oligodendrocytes produce myelin sheath that surrounds axons in the CNS • Myelin • Oligodendrocyte precursor cells • Demyelination • Dysmyelination
- Myelin - consists primarily of ____. insulating properties help primarily w/ conductivity
- a single oligodendrocyte makes up ____ segments of myelin that wrap around multiple axons (this does NOT happen in schwann cells - one cell makes ____ myelin component)
- ____ cells - never mature/always undifferentiated
- in MS, when you have damaged myelin, these cells helps repair
• in H&E stains, oligo’s have characteristic appearance of:
◦ conspicuous nuclei w/ white cytoplasm w/ ____ look
• Demyelination - loss of myelin w/ normal axons
◦ stained in purple + yellow dots show chronic plaque of demyelination - scarring; can’t re-myelinate
◦ other yellow dot area shows area trying to re-myelinate; hasn’t reached scar tissue stage yet
◦ Inflammatory cells mediate; MS is prototype of this pathogenesis
• Dysmyelination - myelin sheaths form normally but maintenance is problem - I.e. ____
lipid
multipleone
precursor
fried egg
leukodystrophies
Microglia have multiple roles that include phagocytosis and immune surveillance
• Hematopoietic origin
• Microglial nodules
• derive from ____ lineage - not true glial cells but have hematopoietic stem cell origin
◦ this separates them in classification due to their different origin
• normal state: inconspicuous
◦ activated: act as ____ for immune surveillance + release ____ (particularly against viruses)
• persistent activation -> may have a role in ____
• ____ properties
◦ can recognize damaged tissue + phago it
◦ when they aggregate around necrosis, it’s called a ____
monocyte/macrophage antigen presenting cell cytokines alzheimer's phagocytic
Ependymal cells are epithelial cells that line the ventricles and cover the choroid plexus
• Ependymal cells produce ____
• Cells are ____
• Atrophy
• Histo: single cell lining on the ____
◦ choroid plexus - extend into ventricular spaces as frond-like areas
• pathology/infection -> atrophy
◦ lose their cytoplasm + become flattened
◦ says here that they’re atrophic (upper lining), but then after this says “and here they’re in normal state” but I can’t see his laser go anywhere…. :/ feelsbadman
◦ causes: ____ - stretching due to increased ventricular spacing
•
CSF
cuboidal to columnar
choroid plexus
hydrocephalus
Hydrocephalus is an abnormal accumulation of CSF in the ventricles
• Clinical presentation varies with age
• Head ____ in infants increases
• CSF flows through series of openings in brain then moves out to the ____ space where it’s reabsorbed into the venous system
◦ if any obstruction of this flow, then accumulation under pressure of CSF -> hydrocephalus
◦ Brain can accommodate quite a bit of ventricular dilation without neuronal dmg, but if it’s persistent
enough eventually it will cause irreversible brain damage
◦ Infants: skull can expand quite alot b.c sutures are not ____ yet
‣ abnormal enlargement of head with ____ deviation of eyes
‣ vomiting, sleepiness, irritability
◦ Adults: not as much enlargement of the skull, but can get headache, vomiting, changes in vision,
downward eye deviation
‣ changes in ____ + memory loss
circumference subarachnoid ossified downward personality
Hydrocephalus can develop for a variety of reasons, sometimes as part of another condition
• Congenital
• ____
- Acquired
- ____
• this is a more common congenital anomalies affecting nervous system
◦ caused by aqueduct stenosis - passageway b/t ____ ventricle; when it becomes narrowed or
blocked, can develop congenital version of hydrocephalus
‣ ____ stenosis is most common congenital form
• Acquired hydrocephalus - caused by ____ of the meninges
◦ the exudate blocks the normal flow of the ventricular system
• left image: early stage of meningitis -> right is ____ of ventricular systems
aqueduct stenosis
meningitis
third and fourth
x-linked
inflammation
enlargement
Optimum treatment for hydrocephalus is controversial for infant hydrocephalus
• CSF ____
• Endoscopic third
ventriculostomy
• Complications
• traditional treatment = craniotomy - draining of the fluids in brain via a cut hole
• CSF ____ - is now the MOST COMMON
◦ diverts CSF from ventricles down into the ____ cavity - catheter runs subcutaneously with valve in between ventricular + distal catheters.
◦ Ventricular Peritoneal Shunt (VPS)
◦ common failure is due to ____ - occurs in up to 40% of children within first 2 days of placement
• Endoscopic third ventriculostomy - pinpoint hole in ____ ventricle to let excess CSF drain out
into other area of the brain
◦ high rate of ____ failure esp in infants
• Complications - see sub-bullets above
shunting shunting peritoneal mechanical obstruction third early
Meningitis is inflammation of the lining around the brain caused by infectious agents
- Children under age of ____ are highest risk for infection
- Pneumococcal caused by ____
- Meningococcal caused by ____
- ____
can be caused by bacteria, fungi, virus, or parasitic
◦ Bac meningitis is much worse/fatal than viral meningitis
H. influenza type B - more often in ____ globally
◦ more common in adults in the US (younger children usually vaccinated for this strain)
These 3 pathogens all cause meningitis
2
streptococcus pneumonia
neisseria meningitidis
haemophilus influenza type b
infants
Bacterial meningitis is often preceded by \_\_\_\_ illness or a sore throat • Fever, headache, nausea, vomiting • Mental status change • \_\_\_\_ • Nuchal rigidity • \_\_\_\_; bulging fontanelles in children
• Pathogensis
◦ starts as ____ tract infection -> travels through bloodstream + up into brain
• Tx
◦ antibiotics/steroids to counter bad + lower inflammation
◦ children coming into contact w/ sick patients are given ____ as preventative prophylaxis
respiratory
photophobia
hydrocephalus
upper respiratory
antibiotics
Bacterial meningitis is characterized by acute inflammatory infiltrate and ____ purulent exudate
• Exudate can encase ____ nerves
• ____ in the subarachnoid space and in leptomeningeal veins
cloudy, glazing of the b9rain post-mortem (first pic) infiltration of cranial nerves can lead to deficits
◦ nerves most commonly affected are CN ____
‣ Pic: exudate encasing CN’s
◦ Hypoglossal nerve dmg -> paralysis of the tongue; deviates ____ side of damage
◦ (Shows a video); tongue clearly deviating towards right so right sided dmg
◦ exudate can also infiltrate the ____ system -> hemorrhagic infarction
Last pic on right: pathology
◦ ____ of inflammatory cell infiltrate
thick
cranial
neutrophils
3, 4, 6, 7
towards
venous
band
Bacterial invasion of through the blood brain barrier
- Pneumococcal surface protein C binds to ____ receptor on brain endothelial cells
- Pneumococci can also enter in between ____ of endothelial cells
- Antigen Presenting Cells recognize bacterial components and release ____ proteins
• no one really knows how the bac crosses the BBB
◦ Pneumococcus: binding to Laminin protein on endothelial surfaces
‣ ____ on bacteria latches onto endothelial surface where it then releases MMPs to degrade endothelium + enter CSF
◦ Tight junctions can be degraded by bacterial enzymes + can enter this way
‣ (I apologize if this seems somewhat jumpy or unorganized he kinda just starts saying stuff then completely shifts his thoughts halfway through after reading his presentation notes on the comp)
◦ APCs in CSF recognize the bacteria through their ____ + release cytokines -> recruits neutrophils + create inflammatory response
• Question (can’t hear)
◦ this model for pneumococcus is kinda hypothetical because other mechanisms aren’t known but
assumed to be similar
laminin
tight junctions
proinflammatory
PSPC (pneumococcal surface protein C)
receptors
Deficiency in downstream signaling cascade have been associated with invasive pneumococcal disease, including meningitis
• ____ deficiency in children
• Appears specifically important at
____ age
• some children have a predilection for reoccurrence
• Receptors on APCs
◦ Toll receptors - recognize ____ or sugars from bacterial cell wall
‣ upon recognition causes cascade in APC -> production of cytokines that recruit other
inflammatory cells
◦ deficiency in any point in this pathway will prevent proper recruitment of cells
• back to children bullet
◦ IRAK-4 deficiency - predisposed to recurrent ____ infections + meningitis
◦ in children that have recurrent meningitis but intact IRAK-4, they have a ____ defect
‣ something along the cascade has association with recurrence
◦ children > ____ y/o do NOT have fatalities associated w/ bac meningitis + NO report invasive infections
in children > ____
‣ age-related deficiencies - important @ young age
◦
IRAK-4 young pneumolysin pneumococcal Myd88 8 q4
Bacterial meningitis can have lasting effects even after infection
• ____ damage, brain damage
• ____ loss
• ____ complications
• Recruited neutrophils cause damage to bacteria but also parenchyma + brain tissues
• ____ - direct cellular dmg to brain parenchyma
◦ long term: neuronal + Brain dmg
‣ hearing loss - not really clear how this is occurring but up to 30% of patients that have had bac meningitis experience uni or bi-lateral hearing loss which is often ____
‣ cochlear involvement may be direct result of CSF to the cochlear peri-lymphatic system
• Strokes
◦ pathogenesis is unclear but thought to be disregulation of ____ + coagulation pathways
neuronal
hearing
cerebrovascular
H2O2
permanent
fibrinolytic
Vaccination is a successful intervention for preventing meningitis globally, but there’s still work to do
- ____ virtually eliminated in high- income countries
- Pneumococcal ____ vaccination has resulted in significant declines in disease beyond age groups targeted for vaccination
- However, epidemics remain a threat in the meningitis belt countries in ____
• Pneumococcal conjugate vaccine
◦ made by linking small conjugate from bacterial sugar coat to protein that child’s immune
system can bind to
‣ ____ on bacterial coat canNOT be detected by child’s immune system so it needs to be conjugated to ____ that CAN be recognized- definition of conjugate
◦ “meningitis-belt” - likely still prevalent due to poor conditions of these countries
‣ difficult to diagnose b.c requires CSF which is expensive to do
‣ also, poor resources + ____ conditions create environment ideal for bac meningitis
H. influenzae
conjugate
sub-saharan africa
sugars
proteins
dusty
Encephalopathy is a term for any diffuse disease of the brain that alters function or structure • Infectious • Metabolic dysfunction • Tumor • Toxicity • Poor nutrition • Lack of oxygen
• Encephalopathy is a generalized term for a diffuse dx that alters function/structure
◦ Caused by many etiologies
◦ Hallmark = altered ____ state
‣ Some dx we discuss later -> clinical presentation = encephalopathy
• Other clinical presentations of enceph: cognitive changes, personality changes and inability to concentrate
◦ Muscle ____ is also seen with enceph
◦ Rapid voluntary ____ movement and tremor/muscle atrophy and weakness
• ____ studies can be used to differentiate bt infectious vs tumor causes of enceph
mental
twitching
eye
blood tests/imaging
Multiple sclerosis is a disease that destroys myelin that disrupts nerve • Early adulthood usually 20 to 40 \_\_\_\_ • Generally increases with increasing \_\_\_\_ from the equator • HLA-\_\_\_\_ • Vitamin D • Smoking risk • Obesity • Infectious • Epstein Barr virus
• We don’t know a lot about MS
• Tends to present early in adulthood, and thinks that it’s caused by geographic/environmental and
genetic factors
• Mainly found in europeans; rare in asians/AA/native Americans
◦ Higher in females than males (3:1)
• Correlation w higher latitudes; the further away from the equator > inc presence and incidence of MS is
found
◦ May be seen in association w lack of ____, but will be a combo of diff environmental factors, but vitamin D is consistent
• Genetic factors -> HLA-DRB1 is related to the prevalence of MS
• ____ has an increased risk for MS
• ____ is associated w a 2-3 fold inc in MS
• Infectious dx -> ____ is controversial, but it has been suspected as a trigger for MS
◦ May be related to ____, normally the bodies immune system attacks infectious
agents, so if a molecular part of your own body resembles a component on a microbe, then both molecules can be targeted by your immune system
‣ A particular protein on that EBV resembles the myelin protein -> so then this AI attack on myelin is triggered by an infection
females distance DRB1 vitamin D smoking obesity EBV molecular mimicry
The clinical courses of MS are purely descriptive
- Clinically isolated syndrome
- Relapsing remitting MS
- Reversible or irreversible
- Secondary progressive MS
- Irreversible
- Primary progressive MS
• MS is divided into different clinical courses, but there isn’t a diff prognosis for these courses
◦ Don’t get caught up in the granular details; be able to distinguish what’s going on bt MS and
Alzheimer’s (i.e., which dx is associated w demyelination in that sense)
• Onset of MS is characterized by an ____
◦ ____ episode of neurological dysfunction due to the demyelinating lesions in the optic nerve (also seen in spinal cord, brainstem and cerebellum)
• A lot of other CNS diseases can present w this so its not ____ to diagnose MS
• You have that pre-symptomatic CIS stage that has that initial presentation (???)
◦ During the disease course of relapsing remitting MS there are further clinical episodes that occur known as ____, and these relapses last for more than 24 hour and occur in ____ of fever and infection
‣ This is where MS can ____ to be suspected
• Symptoms of a clinical attack in relapsing remitting MS tend to show an ____/subacute onset that can worsen over days/weeks
◦ Characterized by occurrences of relapses that occur at irregular intervals that occur w either incomplete or complete neurologic recovery
‣ ____ onset of clinical symptoms -> describes relapsing/remitting MS
• If this continues -> secondary progressive MS -> onset of symptoms are ____
◦ Permanent neurologic defects -> progressive clinical disablity
• Minority of patients have primary progressive MS -> from the start bypass all of the ____ MS and start w perm neurologic deficits for more than a year without relapses
◦ Separate clinical presentation
initial clinical attack (CIS)
unpredictable
easy
relapses absence start acute unpredictable irreversible CIS and relapsing/remitting MS
Neurologic dysfunction of multiple sclerosis is variable and depends on the ____ of demyelinating lesions
• Optic neuritis
• Central scotoma
- Sensory symptoms
- Spinal cord
- Lhermitte’s sign
- Brainstem/cerebellar
- Hearing loss
Optic neuritis ◦ Is the first episode in a large number of patients ◦ Total visual loss in \_\_\_\_ eye ‣ With a \_\_\_\_ spot ◦ Deficiency in color vision ◦ Or pain w eye movement
Sensory symptoms
◦ ____ inflammation
‣ Parasthesia = ____ sign
• Electric shock down the spine when flex the ____
• Seen in sensory symptoms of MS
◦ Reduced pain and light touch sensation -> can worsen w inc body ____
◦ Damage to the brain stem/cerebellar region
‣ Symptoms: facial ____, sensory loss, hearing loss or nausea
◦ Depending on where the damage of the myelin occurs -> corresponds to where the symptoms are
that these patients experience in MS
location
one
blind
spinal cord lhermitte's neck temp numbness
Motor manifestations affect almost all patients during the course of the disease
• Motor manifestations
• Spinal cord
• Brainstem and cerebellar symptoms
Motor manifestations are often characterized by pyramidal signs -> involving cortical spinal tract Classic motor manifestation of MS is the ____ sign and ____ (muscle spasms that have stop- and-go flexing of the muscle)
Shows a video of Babinski sign
◦ 1:04:30 for the video
‣ When touch rod on bottom of foot -> babinski sign the toes curl ____ and the toes
____ (as opposed to the normal toe curling forward reflex) -> indication of a CNS defect
‣ Clonus is another sign of MS -> when dorsiflex the foot -> see a continual ____ (1:07:30)
-> indicates CNS damage
• After an ischemic stroke, so this is a ____ sign but can be indicative of CNS
dysfunction
• Above were the motor symptoms you can see in the spinal cord, in the brain stem has different manifestations:
◦ Involuntary ____ movement - nystagmus (1:09:00 for a video) ◦ Visual phenomena -> objects in visual field oscillate
◦ Double vision
‣ CN ____ palsy
‣ CN VI innervates lateral rectus -> when not contracting properly the eye turns inwards ____ the nose (1:09:30 for a video)
• “Right CN VI palsy; looks straight ahead the right eye is deviated ____, when looks
right the right eye hardly moves, when looks to the left both eyes move ____”
◦ Lose muscle control in arms/legs -> gait disturbance, imbalance and poor coordination
‣ ____ - pt has a hard time turning (video at 1:12:30), and has a tough time touching his nose and then the practitioner’s finger
◦ Develop ____ speech
◦ Loss of complex movements
babinski clonus backwards spread spasm non-specific eye VI towards
inwards
normally
ataxia
slurred
