Note the large defect in the lower back region of this baby. This neural tube defect is so large that the spinal canal is open and the meninges and cord can extend out, making this a meningomyelocele. You may see the term "spina bifida" used to describe a more subtle defect seen on a radiograph in which there is incomplete closure but skin still covers the defect.
The surface of the brain with cerebral edema demonstrates widened gyri with a flattened surface. The sulci are narrowed. Treat with mannitol. If pupil or pupils begin to dilate then hyperventilate. Sometimes need to place ventricular catheter. No role for steroids unless this is vasogenic edema vs. cytotoxic edema.
Papilledema is shown here. Note that the margins of the optic disk are indistinct with blurring, because there is swelling with elevation of the optic nerve head. Any condition that increases intracranial pressure (edema, hemorrhage, mass lesions, etc) will produce papilledema.
Acute brain swelling in the closed cranial cavity is serious. Swelling of the left cerebral hemisphere has produced a shift with herniation of the uncus of the hippocampus (medial temporal lobe) through the tentorium, leading to the groove seen at the white arrow.
The end result of herniation is compression and Duret hemorrhages, as seen here in the pons.
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. Hydrocephalus can be a long-term complication of infection. A basilar meningitis, for example, may lead to scarring that obstructs CSF outflow via the foramina of Luschka or Magendie. Inflammation with scarring of arachnoid granulations at the vertex may diminish CSF absorbtion.
Occurs at areas of turbulent blood flow (branching arteries)
This is an intermediate to remote infarct in the distribution of the middle cerebral artery.
Here is a cerebral infarct from an arterial embolus, which often leads to a hemorrhagic appearance. There is cytotoxic edema which obscures the structures. The acutely edematous infarcted tissue may produce a mass effect. Note the decrease in size of the lateral ventricle on the left, with shift of the midline to the right.
The infarction seen here has punctate hemorrhages. This infarct in the distribution of the middle cerebral artery was caused by an embolus from a left atrial mural thrombus in a patient with atrial fibrillation.
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 intermediate infarct of the frontal lobe shows liquefactive necrosis with formation of cystic spaces as time passes and the process of resolution begins. LIQUEFACTIVE NECROSIS-results from the hydrolytic enzymes and occurs when autolysis and heterolysis prevail over conditions that favor denaturation of proteins which leads to cystic formation of the infarction
Hemorrhages involving the basal ganglia area (the putamen in particular) tend to be non-traumatic and caused by hypertension, which leads to arteriosclerosis that damages and weakens the small penetrating arteries. A mass effect from the collection of blood with midline shift, often with adjancent secondary edema, may lead to herniation.
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.
Here is an incidental non-ruptured berry aneurysm located at the bifurcation of the left middle cerebral and anterior communicating arteries of the circle of Willis at the base of the brain. These aneurysms may be present in 1% of persons. They form at points where there is a developmental weakness in the arterial wall.
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 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 at the base of the brain. As the weak wall of the artery, which lacks an internal elastic lamina and a media, expands to form the aneurysm, there may initially be leakage of blood that produces headaches, but there is risk for sudden rupture to produce a severe headache. The blood irritates the arteries to produce vasospasm and promote cerebral anoxia.
The subarachnoid hemorrhage from a ruptured aneurysm is more of an irritant producing vasospasm than a mass lesion.
Diffuse subarachnoid hemorrhage extends from the base of the brain to the lateral surface of frontal and temporal lobes. Note that there is no blood beneath the dura reflected upwards. A ruptured berry aneurysm with subarachnoid hemorrhage leads to sudden onset of an excruciating headache. The mortality rate with initial rupture is 25 to 50%
The 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.
The characteristic location of the hemorrhage in this brain is consistent with a fall forward resulting in a injury to the inferior frontal and temporal lobes. This has resulted in extensive contusions and subarachnoid hemorrhage.
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.
The skull has been removed to reveal the middle meningeal artery having emerged from the foramen spinosum and branching over the outer dura.
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.
The 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.
One cause for acute 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.
Here is another example of an acute meningitis from bacterial infection. The cerebrospinal fluid (CSF) obtained via lumbar puncture in such cases typically has a low glucose, high protein, and a cell count with many PMN's. A gram stain should be done to identify organisms
In temperate climates of the northern hemisphere, the viral encephalitides have distinct seasonal occurrences that may be helpful in the differential diagnosis. Encephalitis caused by the mosquito-borne and tick-borne arboviruses peaks in the spring and summer, paralleling the periods of activity for their insect vectors. Others, such as herpesvirus infections, may occur year round.
An uncommon but distinctive form of viral infection of the brain is herpes simplex virus encephalitis. The cases are sporadic and can occur in non-immunocompromised persons. HSV infection often produces hemorrhages in the temporal lobe.
There are areas of hemorrhage with brain swelling and a midline shift. This resulted from a disseminated Aspergillus fungal infection in a patient who was markedly neutropenic. The greenish discoloration has resulted from bile pigments (oxidized to biliverdin by formalin fixation) leaking past a blood-brain barrier destroyed by the invasive fungal hyphae.
Progressive multifocal leukoencephalopathy (PML) is an infection of the CNS caused by the JC papovavirus. PML occurs in immunocompromised patients, such as those with AIDS. PML appears grossly as irregular areas of granularity in white matter, which bear some resemblance to the plaques of demyelination with multiple sclerosis.
Raccoons, skunks, and bats
Early evidence of poliomyelitis from Middle Kingdom Egypt ca. 1300 BC. A tracing of one of the figures from the funerary stele of the priest Rom. The figure has a withered right leg and dropped foot, which are typical of poliomyelitis
Polio specifically effects anterior horn cells
THE IRON LUNG RESPIRATORY PARALYSIS(MEDULLA OBLONGOTA)
LOCOMOTOR ATAXIA- posterior column infection : loss of position sense and pain sensation as seen in advanced neurosyphilis
ARGYLL ROBERTSON PUPIL-Light-Near dissociation (pupil constrict on convergence but not light
The prion diseases have also been referred to as transmissible spongiform encephalopathy agents. The first of these diseases, scrapie, was recognized to be transmissible in sheep in the 1930s. The latest epidemic of BSE in Britain, referred to by the lay public as "mad cow disease," is believed to have been transmitted to humans via the ingestion of contaminated beef resulting in a progressive dementia that has been named new variant CJD (nvCJD). The disease caused by nvCJD occurs in younger people and disease progression is slower. Kuru is of historical interest because it was the first human prion disease to be recognized as transmissible. It occurs in the Fore Indians of New Guinea beginning with gait, trunk, and limb ataxia and involuntary movements (myoclonus, chorea, tremor) followed by dementia at a later date. Because it is transmitted primarily through cannibalistic rituals, which are now restricted, kuru is rare.
One of the important characteristics of these agents is that they do not contain detectable nucleic acids (DNA, RNA) but do contain a protein, the prion protein (PrP), that must be transmitted for disease to occur. This finding led to the "prion" terminology, which was derived from "protein" and "infectious." There is no specific treatment for the various prion diseases. However, the agent (prions) can be disinfected with various sterilization procedures.
The "holes" in the cortex of the cerebrum seen here represent a spongiform encephalopathy known as Jacob-Creutzfeldt disease (CJD). This is a form of rapidly progressive dementia. It is due to a poorly understood prion protein that has infectious potential, but the cases appear sporadically (1 in a million). SWISS CHEESE APPEARANCE
Seen here is 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.
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 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.
Note how this meningioma beneath the dura has compressed the underlying cerebral hemisphere. Rarely, meningiomas can be more aggressive and invade.
This discrete 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 mass lesion here is arising in the acoustic (eighth cranial) nerve at the cerebellopontine angle. This is a schwannoma. Patients may present with hearing loss. These benign neoplasms can be removed. May be referred to as acoustic neuroma
Note café-au-lait spots
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 increased IgG that demonstrates oligoclonal bands on electrophoresis is very consistent with this diagnosis.
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 type (Alzheimer disease).
The cortical atrophy leads to compensatory dilation of the cerebral ventricles known as "hydrocephalus ex vacuo".
The characteristic microscopic findings of Alzheimer disease include neuritic plaques ("senile plaques") which are extracellular deposits of the amyloid beta-protein (Aｧ). In the more numerous, smaller diffuse plaques this Aｧ alone is present as filamentous masses. However, the diagnostic neuritic plaques also have dystrophic dilated and tortuous neurites, microglia, and surrounding reactive astrocytes.
This is a neurofibrillary "tangle" of Alzheimer disease. The tangle appears as long pink filaments in the cytoplasm. Neurofibrillary tangles are composed of cytoskeletal intermediate filaments in the form of hyperphosphorylated microtubule-associated proteins known as tau.
Scientists have discovered that the abnormal protein produced by the Huntington's disease gene, which contains an elongated stretch of amino acids called glutamines, binds more tightly to HAP-1 than the normal protein does. This molecular partnership may contribute to the debilitating symptoms associated with the disease./When the HD gene was found, researchers discovered that HD belongs to a newly discovered family of diseases called "triplet repeat" diseases. A gene's DNA bears coding molecules which are translated into specific amino acids, the building blocks of proteins. In the HD gene, the coding molecules cytosine, adenine, and guanine (CAG) - the triplet - repeat in a stretch more than they do in the normal gene. Normally the CAG sequence repeats between 11 and 30 times. People with HD may have CAG repeated between 36 and 125 times. The onset of the disease generally is in the 30s and 40s (with a range of age 2 to 82), but more than 60 repeats of CAG often are associated with an onset of HD before age 20. With the majority of people who have fewer than 60 repeats, there is great variability. A person can have 40 CAG repeats in his or her DNA sequence and have onset at age 17 or 70. On average, however, a feature dubbed "genetic anticipation" occurs. Each time the unstable DNA is passed on to offspring, the affected person experiences an earlier onset. ﾊﾊﾊﾊﾊ Scientists discovered that the HD gene produces a protein called huntingtin. This protein occurs in cells and is found throughout the body -- not just in the brain where there is heavy damage. The abnormal form of huntingtin is likely to have a mutated structure, perhaps causing an altered "polar zipper." This term is used to describe how the structure's string of polar or waterloving amino acids folds together like a zipper (see illustration) which may change its interactions with other proteins.
Atrophy of the head of the caudate nucleus leads to ventricular enlargement.
During movement, signals pass from the brain's cortex, via reticular formation and spinal cord (pathway A), to muscles, which contract. Other signals pass, by pathway B, to the basal ganglia; these damp the signals in pathway A, reducing muscle tone so that movement is not jerky. Dopamine, a nerve transmitter made in the basal ganglia, is needed for this damping effect. Another transmitter, acetylcholine, inhibits the damping effect.Parkinson's disease. In Parkinson's disease, degeneration of parts of the basal ganglia causes a lack of dopamine within this part of the brain. The basal ganglia are thus prevented from modifying the nerve pathways that control muscle contraction. As a result, the muscles are overly tense, causing tremor, joint rigidity, and slow movement. Most drug treatments increase the level of dopamine in the brain or oppose the action of acetylcholine.
The loss of pigmentation in the substantia nigra of the midbrain at the left in a patient with Parkinson disease is contrasted with a normal midbrain at the right.
At the left, normal numbers of neurons in the subtantia nigra are normally pigmented. At the right, there is loss of neurons and loss of melanin pigmentation with Parkinson disease.
A variety of cellular insults may intersect, leading individually or in concert to neuron degeneration, neuron death and finally ALS. A faculty gene (1) and excess glutamate (2) may lead to damaging free radicals (3), which can harm the nerve cell's DNA. Glutamate also may lead to the production of detrimental calcium, which can churn out its own supply of DNA-harming free radicals. The free radicals also may injure neurofilaments (4), proteins that serve as the skeleton of the cell. In addition, the immune system (5) may be involved in harming neurons. Abnormalities can lead to an accumulation of the toxic calcium.
Grossly, the corticospinal tracts in these cross sections of thoracic spinal cord demonstrate a pale white appearance from the degeneration resulting from amyotrophic lateral sclerosis (ALS).
Amyotrophic lateral sclerosis (ALS) is uncommon. It usually 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 with ALS demonstrate atrophy, as seen here in comparison with a normal spinal cord motor nerve roots.
NEUROPATHOLOGY LECTURE 2009*
MEDEX 452: Pathophysiology for Primary Care
Henry Stoll, PA-C
Cerebral contusions. Primary impact damage has caused severe hemorrhagic contusion of the
left frontal lobe (C) - coup lesion, with smaller contusions on the right parietal lobe (P) contrecoup lesion. Swelling of the left side of the brain has caused cerebral herniation with
compression of the midbrain
Major causes of viral encephalitis in the United States
Nationwide (esp. south and
California/La Crosse Central and eastern US
Atlantic and Gulf coasts
Colorado tick fever
Texas and Florida
Seasonal variation in infections capable of
causing viral encephalitis
Propagation of scrapie PrP in neurons of the brain apparently occurs via
a domino effect on an internal membrane. A favored hypothesis holds
that the process begins (a) when one molecule of scrapie (red) contacts
a normal PrP molecule (brown) and (b) induces it to refold into the
scrapie conformation. Then, the scrapie particles attack other normal
PrP molecules (c). Those molecules, in turn, attack other normal
molecules and so on (broken arrow) until scrapie PrP accumulation
reaches dangerous levels (d).
Characteristics of prion diseases and agents
Prolonged incubation period of months to years
Progressive course of weeks to months to death
No host immune response (except astrocytosis)
Pathologic lesions confined to the central nervous system
No specific treatment
Causative agents (prions) have specific properties:
No detectable nucleic acid
Resistant to alcohol, formalin, heat, ultraviolet (UV) irradiation, nucleases*
Susceptible to proteolytic enzymes, denaturing agents, organic solvents**
Steam autoclaving 1 hour at 132ºC
Immersion in 1N NaOH for 1 hour at room temperature
*Agents that hydrolyze or modify nucleic acids.
**Agents that digest, denature, or modify proteins
TWO OR MORE OF THE FOLLOWING
>6 Cafe’-au-lait spots
>2 Lisch nodules
1st degree relative
Bilateral eigth nerve masses
two of the follwing
Characteristics of Parkinsonism
Freezing of gait
Loss of postural Kyphosis
Wernicke's encephalopathy. In this coronal section of brain the mammillary bodies (arrows)
show petechial hemorrhages characteristic of acute Wernicke's encephalopathy caused by