In the name of GOD. Neuropathology Here is the vertex of a normal brain. Note the regular pattern of...

In the name of GOD

Neuropathology

Here is the vertex of a normal brain. Note the regular pattern of gyri and sulci. A sulcus is the depth between one gyrus and the next. The thin meninges cover the surface, but have been stripped away over part of the central fronto-parietal region at the right to reveal more clearly the sulci. The central fissure is where the extension of the dura between the hemispheres, called the falx cerebri, would be.

The meninges have been removed at the vertex of a normal brain to reveal the A

Rolandic fissure with the precentral gyrus (motor cortex) and the postcentral gyrus

(somesthetic cortex).

tumors

This circumscribed reddish-yellow firm neoplasm beneath the dura next to the falx

is a meningioma. The superior parasagittal location is quite common.

Here is another benign meningioma beneath the dura. These neoplasms are slow growing, but may

reach a large size before symptoms lead to detection .

Note how this meningioma beneath the dura has compressed the underlying cerebral

hemisphere. Rarely, meningiomas can be more aggressive and invade.

this meningioma is composed of whorled nests of cells. A variety of

patterns are possible.

Here is an ependymoma arising from the ependymal lining of the fourth ventricle above the

brainstem and bulging toward the cerebellum. Ependymomas are benign histologically.

This horizontal (CT scan) section of the brain

reveals a large ependymoma of the fourth ventricle.

The microscopic appearance of an ependymoma reveals a rosette pattern with the cells arranged about a central

vascular space .

Myxopapillary ependymoma

which is typically found arising in the filum terminale of the spinal cord. Note the cells around papillations that have a myxoid connective tissue core. Surgical removal is made easier if this tumor has not grown around nerve roots of the cauda equina.

medulloblastoma.The irregular posterior

fossa mass that is seen here near the midline of the cerebellum and extending into the fourth ventricle above the brainstem is a medulloblastoma. This is one of the "small round blue cell" tumors and it most often occurs in children.

Here is the microscopic appearance of a medulloblastoma with small round

blue cells.

Here is a cystic astrocytoma of the cerebellum in a child. Most childhood brain tumors arise below the tentorium, which is the reverse of the adult. Gliomas in children, therefore, are most common in the posterior fossa. They are often cystic (so-called "juvenile astrocytomas")

This discreet firm neoplasm was removed from the surface of a peripheral nerve. It is a

schwannoma (neurilemmoma) which arises from the nerve sheath Schwann cells.

The cut surface of a schwannoma is similar to that of many mesenchymal

neoplasms, with a "fish flesh" soft tan appearance.

These are the classic microscopic appearances of a

schwannoma, which is benign. Note the more cellular "Antoni A" pattern on the left with palisading nuclei

surrounding pink areas (Verocay bodies). On the right is the "Antoni B" pattern with a looser stroma, fewer cells,

and myxoid change.

This glioma of the cerebral hemisphere demonstrates a mass effect. Note the variegation of the neoplasm,

with areas of red, tan, white, and brown

Even if a glioma is "low grade" it can still be bad, depending upon the location. This glioma of the brainstem is in the worst

possible location-- it cannot be resected.

This sagittal section of brain demonstrates a large brainstem glioma. Most gliomas are

astrocytomas.

This glioma is arising in the cerebral hemisphere. As in most gliomas, it is difficult to

tell where the margin is.

This astrocytoma demonstrates increased cellularity and pleomorphism, as compared to

normal brain. Note the very pleomorphic cell in the center .

This is the worst possible form of glioma--a

glioblastoma multiforme (GBM). These neoplasms are quite vascular with prominent areas of

necrosis and hemorrhage. Note how this one has crossed the midline to the opposite hemisphere.

This glioblastoma multiforme (GBM) demonstrates marked cellularity with marked hyperchromatism and

pleomorphism. Note the prominent vascularity as well as the area of necrosis at the left with neoplastic cells

palisading around it.

Here is another example of pseudopalisading necrosis of neoplastic cells in a glioblastoma

multiforme (GBM). The cells of a GBM can infiltrate widely, particularly along white matter tracts, and

even through the CSF.

At the left is seen a

metastasis from a lung carcinoma. Metastases most often appear at the border of the grey and white matter in the distribution of the middle cerebral artery, as in this case, because that is where the blood flow (vascular distribution) is most likely to take metastases.

Oligodendroglioma

Oligodendroglioma

Oligodendroglioma

CNS Hemorrhage

The large hemorrhage in this adult brain arose in the basal ganglia region of a patient with hypertension. This is one cause for a "stroke ."

Hemorrhages involving the basal ganglia area (the putamen in particular) tend to be non-traumatic and caused by hypertension, which damages and weakens the small penetrating arteries. A mass effect with midline shift, often with secondary edema, may lead to herniation.

A blood clot is seen over the external surface of the dura. Thus, this is an epidural hematoma. Such a location for hemorrhage is virtually always the result of trauma that causes a tear in the middle meningeal artery.

11The dura has

been reflected back (with a small portion visible at the lower right) to reveal a subdural hematoma. Such a blood clot is usually the result of trauma with tearing of the bridging veins.

The dura has been reflected above to reveal the bridging veins that extend across to the superior aspect of the cerebral hemispheres. These can be

torn with trauma, particularly if there is significant cerebral atrophy that exposes these veins even more.

Here is a bilateral chronic subdural hematoma. The blood clots are brown to tan because of organization. Since the bleeding is venous, subdurals can form more slowly and insidiously than clots from arterial hemorrhages. Subdurals are most common in the very young and the elderly.

The white arrow on the black card marks the site of a ruptured berry aneurysm in the circle of Willis.

This is a major cause for subarachnoid hemorrhage.

The circle of Willis has been dissected, and three berry aneurysms are seen. Multiple aneurysms are seen in about 20-30% of cases of berry aneurysm. Such aneurysms are "congenital" in the sense that the defect in the arterial wall is present from birth, but the actual aneurysm takes years to develop, so that rupture is most likely to occur in young to middle age adults.

The subarachnoid hemorrhage from a ruptured aneurysm is more of an irritant producing

vasospasm than a mass lesion.

Another cause for hemorrhage, particularly in persons aged 10 to 30, is a vascular malformation. Seen here is a mass of irregular, tortuous vessels over the left posterior parietal region.

The intraventricular and intracerebral hemorrhage seen here was due to a ruptured vascular malformation. The hemorrhage from such a lesion (which is most often histologically an arteriovenous malformation--AVM) can be intracerebral or extend into ventricles or subarachnoid space.

The microscopic appearance of this vascular malformation reveals the dilated, tortuous,

worm-like vascular channels. Such lesions may bleed a small amount and be the cause for a

seizure disorder .

The characteristic location of the hemorrhage in this brain is consistent with a fall backwards resulting in a

contrecoup injury to the inferior frontal and temporal lobes. This has resulted in extensive contusions and

subarachnoid hemorrhage .

A coronal section through the frontal lobes reveals extensive contusions involving the inferior gyri. This was a contrecoup

injury from a fall in the bathtub by an elderly person.

he orange-brown, scalloped appearance of these lesions is consistent with old contusions. The resolution left behind hemosiderin from the

hemorrhage that produces the orange-brown staining .

Seen here are remote contusions, mainly of the right inferior frontal lobe. The crests of the gyri

are most susceptible to the traumatic forces.

The lesions seen here are the result of extensive blunt force trauma to the head in a vehicular accident. Mainly the gyri

are affected with hemorrhage from contusions and lacerations.

The extensive white matter petechial hemorrhages seen here are typical for fat embolism syndrome. Interestingly, neurologic signs and symptoms usually appear about a week after the initiating event, such as long bone fractures in a vehicular accident.

The arteriolar sclerosis that results from chronic hypertension leads to small lacunar infarcts, or "lacunes", one of which is seen here in the pons. Such lesions are most common in basal ganglia, deep white matter, and brain stem.

An acute cerebral infarct is seen here. Such infarcts are typically the result of arterial

thrombosis or embolism.

The bilaterally symmetric dark discolored areas seen superiorly and just lateral to the midline represent recent infarction in the watershed zone between anterior and middle cerebral arterial circulations. Such watershed infarctions can occur with relative or absolute hypoperfusion of the brain.

This is an intermediate to remote infarct in the distribution of the

middle cerebral artery.

A thrombosis of the internal carotid artery is seen here. Arterial thromboses are far more common in the brain than venous thromboses (by a ratio of about 100 to 1).

This angiogram demonstrates an embolic obstruction of a branch of the left common

carotid artery just past the first main bifurcation.

This intermediate infarct of the frontal lobe shows liquefactive necrosis with formation of

cystic spaces as resolution begins.

Here is a cerebral infarct from an arterial embolus, which often leads to a hemorrhagic appearance. There is edema which obscures the structures. The acutely edematous infarcted tissue may produce a mass effect. Note the decrease in size of the ventricle on the left with shift of the midline.

The infarction seen here has punctate hemorrhages. This infarct was caused by an

embolus.

The neurons are the most sensitive cells to anoxic injury. Seen here are red neurons which

are dying as a result of hypoxia.

This cerebral infarction demonstrates the presence of many macrophages at the right which are cleaning up

the lipid debris from the liquefactive necrosis .

The surface of the brain with cerebral edema demonstrates widened gyri with a flattened

surface. The sulci are narrowed.

Acute cerebral swelling can also often produce herniation of the cerebelllar tonsils

into the foramen magnum. Note the cone shape of the tonsils around the medulla in

this cerebellum.

The end result of temporal medial lobe herniation is compression of the brainstem (midbrain and pons) and stretching of small arterial branches to cause Duret hemorrhages, as seen here in the pons.

Infections

Infections

One cause for acute brain swelling is infection. The yellow-tan clouding of the meninges seen

here is due to an exudate from acute meningitis.

The yellow-tan exudate of acute bacterial meningitis seen here

obscures the sulci.

This is another case of acute meningitis. It is important to make the diagnosis and begin antibiotic treatment as soon as possible. Clinical signs may include: headache, neck stiffness (from irritation of spinal nerve roots), fever, and clouded consciousness.

Here is another example of an acute meningitis from bacterial infection. The cerebrospinal fluid (CSF) in

such cases typically has a low glucose, high protein, and many PMN's. A gram stain should be done to

identify organisms .

Microscopically, a gram stain reveals gram negative diplococci within a neutrophil, typical for Neisseria meningitidis. Gram stain and culture can be performed on cerebrospinal fluid obtained via lumbar puncture. A variety of bacteria can cause meningitis, but several are more common, and have an incidence more frequent at certain ages:

Disseminated infections can be seen in immunocompromised hosts.

Such infections can include fungi. Seen here are branching hyphae of

Aspergillus invading a cerebral vessel. Aspergillus likes to invade vessels and produce hemorrhage and thrombosis

The hemorrhages seen here in the temporal lobe are due to Herpes simplex virus infection.

Viral infections produce mononuclear cell infiltrates microscopically.

cerebral abscess. There is a

liquefactive center with yellow pus surrounded by a thin wall. Abscesses usually result from hematogenous spread of bacterial infection, but may also occur from direct penetrating trauma or extension from adjacent infection in sinuses.

Congenital Malformations

Note the marked dilation of the cerebral ventricles. This is hydrocephalus. Hydrocephalus can be due to lack of absorption of CSF or due to an obstruction to flow of CSF

Anencephaly is absence of the fetal cranial vault. Exposure of cerebral tissue to amniotic fluid precludes brain development. Anencephaly is a form of neural tube defect that is typically an isolated birth defect that is not related to chromosomal abnormalities.

The absence of the fetal cranial vault in anencephaly is shown here. The incidence of anencephaly, one form of neural tube defect, has been reported to occur as frequently as 1 to 5 in 1000 live births in the past. However, dietary folic acid supplementation by mothers-to-be before and during pregnancy can reduce the incidence of such birth defects. The rate of anencephaly is now less than 1 in 10,000 live births in some places.

This large mid-thoracic meningomyelocele is another form of neural tube defect (NTD). The genetic polymorphisms due to mutations in the methylene tetrahydrofolate reductase gene may increase the risk for NTDs. Folate is a cofactor for this enzyme, which is part of the pathway of homocysteine metabolism in cells. The C677T and the A1298C mutations are associated with elevated maternal homocysteine concentrations and an increased risk for NTDs in fetuses. Mothers who supplement their diets with folate prior to and during pregnancy can often reduce this risk.

Acquired and Congenital Degenerative Diseases

Here is anterior vermian atrophy of the cerebellum in a patient with

chronic alcoholism.

The small petechial hemorrhages in the mammillary bodies seen here are characteristic

for Wernicke's disease, another complication of chronic alcoholism with thiamine deficiency .

Seen here in white matter is a large "plaque" of demyelination.

The plaque has a grey-tan appearance. Such plaques are typical for multiple sclerosis (MS). These plaques lead to the clinical appearance of transient or progressive loss of neurological function. Since the disease is multifocal and the lesions appear over time, the clinical findings can be quite varied.

Here is a demyelinated plaque in a patient with

multiple sclerosis (MS). The lesions can be seen with MRI scans, but the appearance in the CSF of increased protein from IgG that demonstrates oligoclonal bands on electrophoresis is very consistent with this diagnosis.

Amyotrophic lateral sclerosis

(ALS) is uncommon. It begins in middle age and proceeds to death in several years. There is loss of anterior horn cells, so that patients present with progressive weakness that proceeds to paralysis from neurogenic muscular atrophy. Because of the loss of anterior horn cells, the anterior (ventral) spinal motor nerve roots demonstrate atrophy, as seen here in comparison with normal ventral spinal cord nerve roots

Where are the anterior horn cells in this section of spinal cord? They are absent in a patient with

amyotrophic lateral sclerosis (ALS).

This Luxol-fast-blue stain of spinal cord in a patient with ALS demonstrates lateral column

degeneration with gliosis--the "sclerosis" of ALS.

These enlarged, pale neurons are in a baby with Tay-Sachs disease, which is seen mostly in persons of European Jewish heritage. The disease is often first noticed at an age of 6 months, because the baby is not progressing developmentally

This is an example of neuronophagia in which a dying neuron is

surrounded by microglial cells

The cerebral atrophy seen here mainly in the frontal and parietal regions is characterized by narrowed gyri and widened sulci. The atrophy seen here was due to senile

dementia of the Alzheimer's type

(Alzheimer's disease).

In this case of Alzheimer's disease, there is more marked atrophy seen superiorly and laterally,

with sparing of the occipital region.

The characteristic microscopic findings of Alzheimer's disease include "senile plaques" which are collections of degenerative presynaptic endings along with astrocytes and microglia. These plaques are best seen with a silver stain, as seen here in a case with many plaques of varying size.

The plaques of Alzheimer's disease are seen here with a silver stain. Such plaques are most numerous in the cerebral cortex

and hippocampus. This dementia is marked mainly by progressive memory loss.

This is a neurofibrillary "tangle" of Alzheimer's disease. The tangle appears as long pink filaments in the cytoplasm. They

are composed of cytoskeletal intermediate filaments.

Neurofibrillary tangles of Alzheimer's disease are also seen best with a

silver stain, as shown here .

The very marked frontotemporal atrophy seen here is due to another much less common type of

dementia known as Pick's disease.

The marked atrophy of Pick's disease, a senile dementia, produces "knife-like" thinning of the

gyri in frontal lobes and temporal lobes.

The apparent enlargement of the ventricles seen here is due to atrophy of the head of the caudate from neuronal loss with Huntington's disease, an

autosomal dominant condition characterized clinically by choreiform movements.

At the left, normal numbers of neurons in the subtantia nigra are pigmented. At the right, there is loss of neurons

and loss of pigmentation with Parkinson's disease.

the left, an H and E stain demonstrates a rounded pink cytoplasmic Lewy body in a neuron of the cerebral cortex from a patient with diffuse Lewy body disease, which can be a cause for dementia. Lewy bodies can also be seen in substantia nigra with Parkinson's disease. An immunoperoxidase stain for ubiquitin, seen at the right, helps demonstrate the Lewy bodies more readily.