Neuropathology answers and explanations, April 2018

Dr. J William
1i, B Order a head CT without contrast. He has signs of an ischemic stroke affecting the left MCA
territory, which would likely be due to an embolic or thrombotic event. The CT scan is good in an
acute setting and will be able to pick up major changes such as an acute bleeds, midline shifts due to
oedema or space occupying lesions, etc. The CT scan also helps establish whether he will be a good
candidate for thrombolytic therapy (such as tPA), which should only be used when there are no signs
of bleeding. Contrast dye is not needed in this context.
Thrombotic strokes, are caused by occlusion of medium to large sized vessels (from atherosclerosis,
the main risk factor). They are least likely cause secondary bleeding (unlike embolic strokes) and are
therefore usually the best candidates for thrombolytic therapy (see part ii for explanation).
Side note: Uncomplicated thrombotic strokes (without bleeding, presence of a tumour, etc.) will
often look normal on a CT scan in the early stages of the stroke, which is why physical exam findings
are most useful for diagnosing a stroke.
Major contraindications to thrombolytic therapy:
1. Bleeding in the brain (this is why the CT scan is so important)
2. Symptoms of stroke longer than 4 hours: If tPA is administered too late, the risk of bleeding
following thrombolytic therapy will outweigh the benefits.
3. Patient has a bleeding disorder
4. History of recent surgery major surgery
5. On medication that isn’t compatible with thrombolytic therapy.
6. Prior stroke or head injury in the past 3 months.

MRIs are more sensitive than CT scans, but less practical in an acute setting. They take much longer
to run, are more expensive and also require that patients remain still for long periods of time, which
can be challenging if the patient is obtunded. MRIs are better for detecting bleeds in the chronic
setting and are the standard imaging modality for diagnosing tumours. They are also much better
than CT scans at diagnosing lacunar infarcts.
Choice A, Dexamethasone is useful in patients with increased intracranial pressured from brain
swelling, so it would be premature in this case, since there are no signs of increased ICP in this
patient (such as papilledema). Swelling from oedema usually becomes most pronounced around day
4 of a stroke.
MRAs are most useful for detecting vascular malformations and aneurysms.
Ultrasounds of the head apply mainly to infants, because the ultrasound probe can be placed over
their open fontanelles. If an embolic infarct is suspected, however, neck carotid Doppler ultrasound
and possibly a cardiac ultrasound to look for thrombi or valve vegetations (which can cause septic
emboli) may be needed. Embolic infarcts are more likely to be associated with secondary bleeding
than thrombotic infarcts.

1ii. C. Medium/ large vessel thrombosis. Infarctions can undergo haemorrhagic transformation (i.e.
secondary bleeds) because tissue damaged in ischemia can lead to extravasation of small amounts of
red blood cells resulting in petechial hemorrhage. In some cases these can even lead to formation of
frank hematomas and the risk of this happening is increased by the use of thrombolytic agents.
A is wrong. Secondary bleeding tends to occur more commonly in embolic strokes because it is
thought that the emboli lodged in the vessels are more likely to partially lyse or fragment and
dislodge, moving further downstream, resulting in restoration of blood flow to a damaged area. The
capillary beds in the damaged will be leaky, allowing for extravasation of red blood cells. Reperfusion
injury is less likely to happen in thrombotic strokes. Thrombotic strokes are typically caused by
atherosclerotic occlusion of medium to large vessels (like the MCA, basilar a, vertebral artery, etc.).
Since these occlusions occur at their site of formation, they are less likely to dislodge (unlike embolic
strokes caused by cholesterol and thrombi that have dislodged from an upstream site) and thus less
likely to be associated with restoration of blood flow to the area (unless thrombolytic agents are
implemented).
Choice B is wrong. Global hypotensive events can lead to strokes due to hypoperfusion of the brain.
If the patient survives this event, it typical for restoration of blood flow to occur in the ischemic area.
So like embolic strokes, they are also prone to reperfusion injury and secondary bleeds. Also,
ischemia due to global hypotension typically forms a wedge-shaped lesion in one of the watershed
and the physical exam findings do not support that.
Choice D is wrong. His symptoms do not fit with those of a lacunar stroke. (Lacunar strokes, if
symptomatic, tend to affect smaller areas and will lack major cortical signs like Broca’s aphasia).

2. A. Basal ganglia/thalamic area. These deeper structures of the brain are supplied by small
arterioles that branch directly off of large high flow vessels making them vulnerable in hypertensive
states. Unlike thrombotic strokes, which are due to atherosclerotic occlusion of medium to large
vessels, hypertensive disease primarily affects small vessels, causing hyaline arteriosclerosis (not
atherosclerosis). Other common sites of lacunar infarcts include the internal capsule and pons.
3. B. (Refer to 1b for explanation)
4. b. Fat embolism. Abundant petechial haemorrhage throughout the entire brain is most suggestive
of a shower embolism which is usually due to a fat embolus (note the abundant petechiae in the
figure below). These often arise from fracture of the long bones (the fat is thought to come from the
bone marrow). Patients will usually also have dyspnoea due to emboli in the lungs too. Remember
the three classic clinical signs of a fat embolus (in your notes).

5i. A. Thrombotic. This patient has severe atherosclerosis of the basilar artery and the risk of an
ischemic thrombotic stroke is high.
ii. b. Fusiform aneurysms tend to occur in the setting of atherosclerosis (Remember that
atherosclerosis can lead to vessel occlusion but also causes damage of the vascular wall, increasing
the risk of aneurysm formation). Fusiform aneurysms in the brain are less likely to rupture than berry
aneurysms.
6. False….this is a recent infarct. Gross features: Flattening of gyri, narrowing of sulci, blurring of
grey/white junction. These changes are all due to oedema. Remember a remote infarct (> 6
months) will usually have the gross appearance of a cavitary lesion, since the brain undergoes
liquefactive necrosis.

7i. 10 days age ago: Practically every cell in the picture is an activated macrophage (“foam cell”) and
have the appearance due to accumulation of lipids and other materials from dying neurons. It is
hard to see the cytoplasm in resting macrophages. Macrophages usually peak in number around 1-2
weeks after which, they start to gradually decrease in number and become outnumbered by
astrocytes.
ii. Less than 24 hours: Note the apoptotic (red) neurons that have very dark shrunken (pyknotic)
nuclei and have pink cytoplasm. Normal neurons have dark blue cytoplasmic granules known as Nissl
substance or Nissl bodies (which represent the rough endoplasmic reticulum). Nissl bodies are
usually acidic (i.e. basophilic) due to their high nucleic acid content, so they will be attracted to basic
dyes like haematoxylin. Dying neurons lose their nucleic acids and thus become more acidophilic (i.e.
eosinophilic)…hence the appearance of the red neurons.

8. C. The figure shows a watershed infarct. These are caused by global cerebral hypoperfusion and
typically occur in the border zone (watershed zone) between two major vascular territories (in this
case, the ACA and MCA territories) Also, note the secondary hemorrhage from reperfusion injury in
the figure. Watershed infarcts tend to be wedge-shaped and can also be bilateral.
9. B. Embolus from left atrium Note the petechial haemorrhages in the figure that appear to be in
the distribution of the middle cerebral artery. This would happen more often with an embolic stroke
(which often is associated with reperfusion injury) rather than a thrombotic strokes due to an
occluding thrombus in the MCA. An embolus from the internal carotid artery could also cause the
findings in the figure but it was not listed as a choice. Patients with conditions like atrial fibrillation
are at increased risk of forming atrial thrombi.
(Note that the secondary haemorrhage associated with an ischemic event looks very different to the primary
CNS bleeds. The former usually manifests as punctate/petechial hemorrhage whereas the primary CNS bleeds
(e.g. Due to aneurysmal rupture, trauma, etc.), look very different and show pooled collections of blood (i.e.
hematomas).

10. Only D is true. The figure shows a lacunar infarct (arrows). Hypertension is the biggest risk
factor, and small-sized vessels are usually affected, especially the ones that branch off of large
vessels. Pure motor strokes can result from lacunar infarcts that involve the posterior limb of the
internal capsule. However, many lacunar strokes are asymptomatic.
11. C
12. c. Carotid Doppler US. The patient has experienced several TIAs. One that appears to involve
the right MCA territory and the other (known as amaurosis fugax) that appears to involve occlusion
of the right retinal artery which is a branch of the ophthalmic artery. Assuming that these TIAs share
the same underlying cause, then the best explanation would be emboli from the internal carotid
artery, which is the most common source of atheroemboli to the brain. The other possible sources
of emboli include clots from the left atrium/ventricle or septic emboli from an infected heart valve.
Despite the normal cardiac exam, these should still be part of the differential.
ii. Refer to your notes for the various types of interventions available for patients with occlusion of
the internal carotid artery. (E.g. endarterectomy, stenting, etc.).
 Figure showing vascular distribution of
carotid artery. (Note the ophthalmic
artery and the MCA both branch off of
the internal carotid artery so if both
arteries show signs of occlusion at
different times, it would most likely be
due to an embolus from a more
proximal source (like the internal
carotid arteries), unless there was more
than one cause.

13. The figure shows an epidural hematoma. Note the smooth lens-
shaped appearance typical of these bleeds. Two other examples are
shown in the adjacent figures. Epidural hematomas will not traverse
the midline. These are often caused by skull fractures from blunt
force trauma and symptoms typically occur within 24 hours.
i. False, ii. False, iii. True. Iv. False, V. True. VI false (middle meningeal artery, not the MCA). (Make
sure that you understand and can explain the differences between epidural hematomas and subdural
hematomas, especially in terms of clinical presentation, risk factors, vessels involved, gross
appearance and radiologic appearance)

14. i. Subdural hematoma. These tend to be crescent-shaped on

imaging and usually do not accumulate as rapidly as epidural
hematomas (they can take hours to months to manifest
symptoms). Two other examples of subdural bleeds are shown in
the adjacent figures. Also, if you are given a clinical history of a
bleed with symptoms that manifest slowly over time, this is far
more likely to be a subdural bleed than an epidural bleed. The
CT figures on the right show examples or more recent subdural bleeds.

Ii. Atrophy. Atrophy makes the bridging veins (shown in

adjacent figure) more susceptible to shearing forces, which is
why elderly individuals are more prone to getting subdural
bleeds.
Iii. A subfalcine herniation. (Side note: Subfalcine herniations
can also be seen with strokes affecting the MCA territory due to
oedema on the affected side)

15. iD The figure shows an intracerebral/intraparenchymal hemorrhage complicated by secondary

rupture into the ventricles causing a subarachnoid bleed. Primary subarachnoid bleeds are less
likely to rupture into the parenchyma, which is why answer D is preferred over B.
ii. Hypertension (due to rupture of a Charcot Bouchard aneurysm)
iii. Vasospasm (caused by extravasated blood), Compression of vessels by expanding clot, etc.
16i. d, subarachnoid haemorrhage. ii. Rupture of a berry aneurysm. iii. The picture of the CSF was
accidentally cut off, but showed evidence of a very recent bleed (the colour will be pink).
(**you should also be able to explain the difference between a traumatic tap and a subarachnoid
bleed as well as the significance of Xanthochromia, explained in notes)

17 b. The figure shows multiple contrecoup contusions and their location indicates that the impact
was in the occipital region which typically causes contrecoup bruising of the brain at the tips of the
frontal lobe and tips of the temporal lobe.
“A” is wrong. This type of injury usually causes an epidural bleed (from a skull fracture, causing
damage of the middle meningeal artery). C. describes a subarachnoid bleed. D is bacterial
meningitis. E. describes a patient at risk of developing lacunar infarcts and intraparenchymal bleeds.
18, Both pictures represent subarachnoid bleeds. Blood pooling at the base of the brain (in the
second picture) is usually seen in the setting of a ruptured Berry aneurysms in the circle of Willis.
19. d. Recent subdural hematoma. Note the difference between the subdural hematoma in # 14
and #19. The blood on CT scan of # 14 is dull and represents a chronic bleed, whereas the blood in
#19 is bright because it shows an acute bleed.
20. D. Transtentorial/uncal herniation. (Refer to your notes for the classical clinical signs associated
with an uncal herniation)
ii. Duret’s haemorrhages.
iii. B, This patient had an uncal herniation on the left causing damage of the left oculomotor nerve.
This will result in an ipsilateral fixed and dilated (“blown”) pupil. With further nerve damage, there
will also be ptosis and impairment of extraocular movements. The affected eye will point “down and
out” since the lateral rectus and superior oblique muscles will no longer be opposed.
Panel a. shows a patient with damage to the left lateral rectus muscle, innervated by CN VI.
Panel c. shows a patient with left sided ptosis and a constricted left pupil. This is a classic finding in
Horner syndrome which is caused by impairment of the sympathetic ganglion. Panel d. is subtle and
the most difficult of the four to diagnose clinically. It shows a child with left CN IV damage which
affects the function of the superior oblique.

21. The figure depicts hyaline arteriosclerosis (or lipohyalinosis) caused by hypertension-related
damage. This pathology can lead to vascular occlusion and lacunar infarcts and can also lead to
weakening of the wall with formation of Charcot Bouchard aneurysms. When the CB aneurysms
rupture, they can cause life threatening intraparenchymal bleeds.
22. A. The first panel shows that she cannot close her right eye and the second panel shows that she
has problems smiling on the right side of her face. Therefore, she has impairment of facial nerve
innervation to both the upper and lower right half of the face. Of the
choices given, a mass in the right cerebellopontine angle would be
the best answer (Bell’s palsy would have been another possible
answer, if given as a choice). The classic mass arising in this area is
the acoustic neuroma (schwannoma) which involves CN VIII.
However, if this mass is large enough, it can also compress CN VII.
The fact that the upper half of her right face also shows paralysis
makes cortical damage (such as with an MCA stroke) or a
corticobulbar tract lesion less likely. Remember that CN VII
innervation to the upper half of the face receives bilateral input from
the corticobulbar fibres, so patients with MCA strokes may have
hemiparesis of the lower half of their face, but the upper half should
be spared.

23. B. A stroke involving the posterior cerebral artery territory. Once again, the optic nerves get dual
innervation from both sides of the occipital cortex so a lesion involving the visual cortex is unlikely to
cause complete loss of vision in one eye while sparing the other. All the other examples are of lesions
that occur somewhere between the eye and the optic chiasm, so even though some of these other
conditions can affect both eyes (like multiple sclerosis which causes an optic neuritis/inflammation of
CNII), it is still possible to get blindness in one eye
24. A. Diffuse axonal injury

TUMOUR QUESTIONS
1. C. Medulloblastoma
2. i. True ii. True. iii. False. iv. True. The most common malignant brain tumour in adults is a
metastatic tumour. Whereas most brain tumours in children are primary v. true. Vi. False. Even
though most primary adult brain tumours do not metastasize, many are still regarded as
malignant because they are locally aggressive. For example, glioblastomas in adults are highly
infiltrative and almost impossible to resect.
3. i. f. Medulloblastoma. These tumours arise in the cerebellum and can compress the fourth
ventricle and impede outflow. Other tumours like Ependymomas and Pilocytic astrocytomas can
have a similar presentation, but the microscopic findings do not fit. /ii. D. Glioblastoma/ iii. G
Pilocytic astrocytoma iv. Schwannoma/acoustic neuroma.
4. B. Meningiomas are derived from meningothelial cells not from glial cells.
5. Craniopharyngioma. These are epithelial tumours arising in Rathke’s pouch remnants. They are
the most common neoplastic cause of hypopituitarism in children.
6. A. Ependymoma. Note the rosettes and pseudo-rosettes. These tumours arise from ependymal
cells and can occlude CSF flow. Also, due to their location, they can also involve the spinal column
by “drop metastasis”.
7. i. Medulloblastoma (note the small round blue cells and pseudorosettes)/ ii. Metastatic
papillary thyroid carcinoma, iii. Acoustic neuroma/schwannoma (note the Verocay bodies) iv.
Pilocytic astrocytoma (These usually arise in the cerebellum. Note the bright eosinophilic Rosenthal
fibres). V. Oligodendroglioma (This is a grade 2 glial tumour. (Note the microscopic “fried egg”
appearance due to the clearing around the nuclei) vi. Glioblastoma (Il-defined infiltrative mass.
Microscopic finding: Pseudopalisading necrosis). Glioblastomas are Grade IV astrocytomas. In glial
tumours, the presence of necrosis is required for this grade. VII. Prolactinoma/Pituitary
macroadenoma

INFECTION AND INFLAMMATION.

1, i.G. Multiple sclerosis. The classic presentation is the relapsing-remitting type where patients
have disease free intervals, followed by periods of disease exacerbation. The MRI shows
periventricular white matter plaques which correspond to areas of demyelination Note how the
white matter areas now looks almost like grey matter, due to demyelination in the figure below.

ii. CSF analysis. Patients may have increased protein levels but more specifically, a protein gel
electrophoresis study should show Oligoclonal bands:

MS is diagnosed based on symptoms, CSF and radiologic findings but there is no

single test that can establish the diagnosis. It is increased in certain MHC
haplotypes and living in Northern latitudes seems to increase the risk of
occurrence

2. B. HSV I . Seizures in a young person along with haemorrhage and necrosis of the temporal lobes is
a classic feature of HSV 1 encephalitis.
Microscopically: Increased lymphocytes, especially around vessels (perivascular cuffing), viral
inclusions, etc.
3. i Giant cell (temporal) arteritis. ii. Temporal artery biopsy iii. Irreversible blindness (due to
inflammation of the ophthalmic artery and its branches.)
4. c. Neisseria M. The petechial hemorrhage and adrenal haemorrhagic infarcts (remember
Waterhouse Friderichsen syndrome) are thought to be caused by DIC. Also make sure you are
familiar with the different CSF findings in the various conditions, such as bacterial meningitis, viral
and aseptic meningitis, multiple sclerosis, etc.
5. e. Treponema pallidum. He has neurosyphilis. This form of tertiary syphilis occurs years following
primary infection. His eye finding is consistent with an Argyll Robertson pupil; his positive Romberg
test shows loss of proprioception, and is one of the manifestations of Tabes Dorsalis. Listeriosis and
streptococcal infections are more likely to produce an acute meningitis. Rabies may have an incubation period
of 1 to 3 months, but then manifests with an acute severe encephalitis. Rubeola (measles) infection in rare
instances, may lead to a subacute sclerosing panencephalitis years later (patients present with spasticity and
seizures).
6. A. CMV is one of the perinatal infections that result in congenital abnormalities: TORCH:
Toxoplasma, Other (Syphilis, Parvovirus B19, and VZV), Rubella, CMV, and HSV

7. i. False. Most prion cases are sporadic. This refers to Creutzfeldt Jacob disease. The prion diseases
caused by eating beef are referred to as the new variant Creutzfeldt Jacob disease (nvCJD), but they
make up only a small percentage of prion cases.
ii. True. The prion protein is a type of chaperonin which is a protein that can change the
conformation of other proteins.
iii. False.
iv. True. The abnormal prion protein is resistant to cellular proteases, which is why it is able to
accumulate in the cell and cause damage. The normal prion protein is protease sensitive, so it gets
degraded after a while.
v. True. Examples included Familial fatal insomnia and GSS.

8, Toxoplasma Gondi. Toxoplasmosis is an opportunistic infection that affects the CNS in patients
with AIDS and also causes severe congenital abnormalities if passed from the mother to her
newborn. Toxoplasmosis produces abscesses that organize on the periphery to produce a bright ring
on CT and MRI. Many other infectious organisms and non-
infectious causes can produce ring-enhancing lesions
(lymphomas, glioblastomas, metastases, etc.) But with a CD4
count as low as 50 cells/mm3, toxo should always be considered
(refer to the table in your notes showing the opportunistic
infections associated with different CD4 count ranges). The
microscopic figure shows a cyst filled with bradyzoites. (A clearer
example of a cyst is shown in the adjacent figure).

9. C. He has rabies. Figure C shows a Negri body in the cytoplasm.

(Panel A is a picture of CMV…..note the opaque dark pink viral inclusions). B depicts a Cryptococcal
infection...an India ink test is used to see the translucent Cryptococcal capsule. D. is HSV…note the
multinucleate giant cells with glassy viral inclusions. E shows a multinucleate giant cell in a patient
with TB.

Extended matching questions:

I. Alzheimer’s. Note the atrophy. ii. Bacterial meningitis. III. This is an intraparenchymal bleed. The
most common cause in the non-traumatic setting would be a ruptured Charcot bouchard aneurysm
that formed in the setting of hypertension. iv. Tonsillar herniation. Subarachnoid bleed. vi. Multiple
sclerosis. Note the periventricular areas of demyelination. vii. Subdural bleed. viii. Old/remote
infarct….these will form a cavitary lesion usually after 5 or 6 months. This type of lesion could also
have represented an abscess, although that wasn’t given as a choice. ix. Duret haemorrhages. X.
subfalcine herniation. xi. CJD…note the vacuolation. xii. AVM…note the abnormal vascular channels.
xiii. Lacunar infarcts. xiv. Epidural hemorrhage.