Exam 1: Congenital Malformations, Hydrocephalus, Perinatal lesions (includes supplemental questions) Flashcards
A newborn infant is born close to full-term with an apparent CNS lesion. He is pictured below. What is the most likely diagnosis?
A. Anencephaly
B. Encephalocele
C. Arnold-Chiari, type 2
D. Dandy-Walker
E. Holoprosencephaly
F. Germinal matrix hemorrhage
B.
Encephalocele
- Note the presence of much of the skull, ears, and eyes. A mesodermal defect led to herniation (extrusion) of the brain through the defect. Thus, the posterior sac would contain brain with hemorrhage and would be covered with skin.
- Contrast this with anencephaly. The defect results from a failure of the neural tube to develop. The cerebral hemispheres (and sometimes the posterior fossa structures) do not form and there is no calverium.
A 7 day-old is examined. Imaging is performed and is shown. What is the most likely diagnosis?
A. Anencephaly
B. Encephalocele
C. Arnold-Chiari, type 2
D. Dandy-Walker
E. Holoprosencephaly
F. Germinal matrix hemorrhage
D.
Dandy-Walker
- results from a failure of the cerebellar vermis (midline) to form. The 4th ventricle thus communicates (i.e. connects) directly with the subarachnoid space. A cyst developed that is filled with CSF. The posterior fossa becomes enlarged. Hydrocephalus is present. The above image shows the large posterior fossa cyst (at arrow in image on left).
- Contrast that to Arnold-Chiari Type II (Infantile) where the posterior fossa is too small. This is associated with herniation of the cerebellar vermis through the foramen magnum and elongation with kinking of the medulla. A meningomyelocele is present in 95% of the cases. Hydrocephalus is also present.
Agenesis of corpus callosum
No connection between cerebral hemispheres
- Normal brain cerebral hemispheres are linked by the corpus callosum.
- This can fail to form (completely or partially).
- Can be clinically normal or with mental retardation
• Associated with other abnormalities
• Lipomas (benign fatty tumors) can be seen in the defect
• Note that in the image there is a total absence of the corpus callosum.
Anencephaly
Absence of (lack of) cerebral hemispheres
- Associated with folic acid deficiency, familial cases
- The neural tube is not closed at the anterior end. This significantly interferes with development of the brain.
- Note the absence of the skull and the mass of primitive neural tissues (area cerebrovasculosa) that replaces the normal brain.
- There is also a skull defect.
Arnold-Chiari, Type I
Herniation of cerebellar tonsils
Arnold-Chiari Type II
Herniation of cerebellar vermis, elongation/kinking of brainstem
*** Symptomatic early in life (infantile) ***
• Posterior fossa is too small and misshapen
• Arnold-Chiari type II is characterized by downward displacement or herniation of the cerebellar vermis and brainstem through the foramen magnum (at the arrows).
• The brainstem is often kinked.
• Hydrocephalus develops.
• A meningomyelocele is present in ~95% of cases.
• Brainstem abnormalities
• In the images note herniation of cerebellar vermis, elongation of medulla through foramen magnum, kinking of lower brainstem/upper spinal cord, hydrocephalus. In most cases, lumbar meningomyelocele is present.
Communicating Hydrocephalus
Enlarged ventricles after meningitis
• Increase in ventricular size/CSF volume
- Communicating Hydrocephalus – CSF absorption disrupted (e.g. meningitis in subarachnoid space); no blockage within brain
- Meningitis
Dandy-Walker
Enlarged posterior fossa, absent cerebellar vermis
- Agenesis of cerebellar vermis (roof of 4th ventricle)
- 4th ventricle connects directly with subarachnoid space creating a cyst
•Posterior fossa is enlarged due to the cyst
•Hydrocephalus
- Can be associated with dysplasia of brainstem nuclei
- Dandy-Walker has enlarged posterior fossa, a 4th ventricular cyst secondary to agenesis of cerebellar vermis , and hydrocephalus. The 4th ventricle can directly communicate with the subarachnoid space. A cysts filled with CSF developed and enlarges the posterior fossa.
- Thus, in Dandy-Walker the posterior fossa is enlarged (due to the cyst formation). In Arnold-Chiari, the posterior fossa is too small (which leads to herniation of the cerebellar vermis and elongation/kinking of the brainstem).
Encephalocele
Herniation of brain through hole in skull
• In this case, the problem is not with closure of the neural tube per se. Rather, the skull fails to completely form. Hence, this is a mesodermal defect. This allows the otherwise normal brain to herniate (i.e. protrude) through the defect. This can be small and of limited consequence or large and incompatible with survival.
Holoprosencephaly
Single ventricle and cerebral hemisphere / absent olfactory bulbs
* common chromosomal abnormality of Trisomy 13 & 18
• A single cerebral hemisphere and ventricle (see left image)
• always with Arrhinencephaly: absence of the olfactory tract (and bulbs)
• Other midline facial abnormality including cyclopia (fused eye); see right image.
Hydromyelia
Enlarged central canal of spinal cord
- Hydromyelia occurs when the central canal is enlarged.
- These cysts can interfere with tracts and other structures causes neurologic deficits.
- a photograph of hydromyelia. The central canal is enlarged. However, there is no extension beyond the central canal.
Hydrocephalus ex vacuo
Enlarged lateral ventricles due to caudate atrophy in Huntington Disease
• Increase in ventricular size/CSF volume
• Hydrocephalus Ex-vacuo – ventricular enlargement secondary to loss of brain substance (volume)
• Degenerative disease (Alzheimer disease)
• Hydrocephalus ex vacuo (Right) results from a loss of brain tissue (e.g. in the basal ganglia in Huntington disease). The ventricles expand secondarily. Compare to normal on the left. This can occur in other conditions with loss of brain substance (e.g. strokes, following brain surgeries/resections).
Thus, the enlargement of the ventricles is due to loss of brain tissue and not to an increase in CSF pressure.
Lissencephaly
No gyri
- In lissencephaly, there is an absence of gyri.
- If there are a few large gyri, this is termed pachygyria.
- The concept is that normal structure is needed for the brain to function normally. If there are too many (with other structural abnormalities) or there are too few gyri, the brain isn’t going to function normally. This can reflect genetic and other conditions.
Meningomyelocele
Spinal lesion with leg paralysis/increased AFP in amniotic fluid
- View of the back: CNS tissue is incorporated in the spinal defect in a meningomyelocele. The CNS tissue has herniated through the spinal defect. This is often associated with neural defects (e.g. bladder or lower extremity deficits).
- Note the lack of bone (arches) posteriorly. This section is from the lower spinal column (note the nerve roots). Although herniation or protrusion of the CNS tissue isn’t evident in this section, the designation of meningomyelocele would indicate involvement (i.e. herniation) of both meninges and CNS tissues in addition to the bony defect.
Micrencephaly (microcephaly)
Too small brain
* common chromosomal abnormality of Trisomy 13
Neuronal Heterotopia
Neurons that failed to migrate / seizures
- Heterotopias result from a lack of neuronal migration. Heterotopias are often accompanied by gyral abnormalities.
- The nodules present on the ventricular surface include neurons that did not migrate to the cerebral cortex. These often act as seizure foci.
- Intellectual disability and other CNS congenital malformations are also common.
Polymicrogyria
Too many gyri / 4-layered cortex
• In polymicrogyria, there is excessive gyration resulting in many (i.e. excessive) small gyri. The cytoarchitecture of the cortex is also altered; the normal 6-layered cortex becomes a 4-layered cortex).
Noncommunicating Hydrocephalus
Hydrocephalus due to stenosis (narrowing) of the cerebral aqueduct
• Increase in ventricular size/CSF volume
• Noncommunicating Hydrocephalus - Block of CSF pathway within brain by tumor, clot, stenosis (cerebral aqueduct), etc.
Syringomyelia
Cystic cavity in the spinal cord
- As the neural tube closes, the central canal of the spinal cord is also formed. This can occur abnormally. Syringomyelia occurs when there are additional cystic spaces within the spinal cord.
- Note that syringobulbia is the same process in the brainstem.
- There is a relationship of syringomyelia** with **Chiari malformation. (Adult Type I)
- a drawing of syringomyelia. Note the cystic space (the syrinx) within the spinal cord. If this is located centrally, pain and temperature would be preferentially affected.
Germinal Matrix Hemorrhage
Occurs exclusively in premature infants
• In premature* infants, germinal matrix hemorrhage can develop. The hemorrhage easily ruptures into the ventricles.
• Can extend to ventricles and subarachnoid space leading to hydrocephalus
*The germinal matrix disappears by birth. (Thus, this is a condition of premature infants, and is no longer present in full-term infants)
Kernicterus
Sequela of Rh-incompatibility* / bilirubin damage because of incomplete BBB
• In newborns, the blood-brain barrier is not complete. If bilirubin is elevated, it can leak through into the brain. Bilirubin is toxic to neurons.
• The bilirubin-stained areas often appear yellow in color.
• Adults with elevated serum bilirubin do not experience kernicterus due to an intact blood-brain barrier.
*Due to medical advances that prevents hemolysis through recognition of Rh mismatches and that can treat hyperbilirubinemia, kernicterus is now rare.
Multicystic encephalopathy
Destruction of grey and white matter
- Anoxic-hypoxic; Without blood flow and/or oxygen delivery, the brain suffers ischemia or infarction of involved areas
- In extreme cases, there is necrosis of both the white and grey matter.
Periventricular Leukocephalopathy
Adult with cerebral palsy with cystic lesions in deep cerebral white matter
• Periventricular leukomalacia** – **Anoxic-hypoxic due to areas of necrosis without blood flow and/or oxygen delivery. The brain suffers ischemia or infarction of involved areas
• In PVL, infarct-like lesions develop in the white matter. These lesions can be seen in older children and adults with cerebral palsy.
A photograph from a 6 day old infant is shown. Kenicterus is present. Which of the following most likely contributed to this condition?
A. Bacterial meningitis
B. Germinal matrix hemorrhage
C. Infection from birth canal
D. Incomplete blood-brain barrier
E. Umbilical cord knot
D.
Incomplete blood-brain barrier
(extra info from slide)
Newborns are at risk for kernicterus due to the incomplete blood-brain barrier. The elevated bilirubin can leak into the brain and injure neurons. Older infants and older individuals are not a risk due to the complete and intact blood-brain barrier.
Accumulation of what substance results in the indicated discoloration?
A. Conjugated bilirubin
B. Copper
C. Hemosiderin
D. Rh antigen
E. Unconjugated bilirubin
E.
Unconjugated bilirubin
(extra info from slide)
See above. Hemolytic anemia secondary to the Rh incompatibility results in elevated unconjugated bilirubin. The incomplete blood-brain barrier contributes to this susceptibility. (Photograph from Robbins, 7th ed.)
At braincutting, a specimen from a 3 year-old girl is examined (right). Diagnosis in the prenatal period would most likely be based on detection of which of the following?
A. Alpha fetoprotein
B. Bilirubin
C. Elevated WBC
D. Folate
E. Trisomy 21
A.
Alpha fetoprotein
(extra info from slide)
Meningomyelocele, a form of spina bifida: The defect has allowed herniation of the CNS tissues. The open spinal defect allows alpha fetoprotein (AFP), a liver protein to escape into the amniotic fluid and maternal blood.
This is often used in prenatal diagnosis of neural tube defects. The microscopic picture shows skin (adjacent to CNS tissue); there is no bone (i.e. spine) as expected.. Image can be found in and an earlier edition of Rubin’s Pathology (see LWW Health Library on ACOM’s electronic resources) .
Compare meningomyelocele (sometimes termed myelomeningocele) with meningocele. In meningoceles, CNS tissue does not herniate. The defect only contains meninges. Thus, neurological deficits typically do not occur with meningocele. Meningomyeloceles often have lower limb deficits and neurogenic urinary bladders.
A brain is examined from a patient with a history of spastic right hemiplegia. What type of hydrocephalus is present?
A. Communicating
B. Ex Vacuo
C. Noncommunicating
B.
Ex Vacuo
(extra info from slide)
The infarcted area in the thalamus/basal ganglia area has resulted in secondary enlargement of the adjacent ventricle. This is due to the loss of tissue from the chronic infarct. It is larger than the ventricle on the opposite side.
The space in the middle is due to separation of the leaflets of the septum pellucidum (cavum septum pellucidum) and is not significant.
Communicating hydrocephalus occurs when the reabsorption of CSF is **blo**cked within the subarachnoid space by pus in meningitis or subarachnoid hemorrhage. There is no blockage of CSF pathways within the brain.
Noncommunicating hydrocephalus occurs when internal CSF flow is blocked. This can be a result of a ventricular tumor, stenosis of the cerebral aqueduct, or another lesion.
A 55 year-old man develops involuntary dance-like movements. His father had died of the same disease at 65. Genetic analysis shows 42 and 9 CAG repeats. Huntington disease is diagnosed. A section of his caudate is shown. What change is present?
A. Cystic infarction
B. Demyelination
C. Gliosis
D. Microglial nodules
E. Neurofibrillary tangles
C.
Gliosis
(extra info from slide)
In Huntington, the neurons in the caudate nuclei degenerate due to the genetic abnormality (increased CAG repeats). The caudate nuclei usually project into the lateral ventricles. In Huntington Disease, that atrophy causes the caudate nuclei to be very smooth and often concave.
This results in hydrocephalus ex vacuo. The ventricles enlarge to take the place of the loss tissue. The bottom photograph is taken from the caudate. Neurons have been lost; the majority of the cells are astrocytes. These astrocytes proliferate and hypertrophy with injury (including neuronal loss). This is gliosis. An immunohistochemically stain for glial fibrillary acid protein (GFAP) would highlight the astrocytes.
The caudate is primarily composed of neurons and not white matter (myelinated tissues). Gliosis can be seen with chronic MS plaques/lesions. However, this is not a primary component of Huntington Disease.
Microglial nodules are often seen with viral CNS infections.
Neurofibrillary tangles are seen with Alzheimer disease. These are best seen with silver stains or with immunohistochemical stains for tau protein.
An archived slide from 1950 shows a section from the spinal cord in poliomyelitis. Several dying neurons are pictured. These neurons are surrounded by a large number of cells with phagocytic properties. What are these cells?
A. Astrocytes
B. Microglia
C. Lymphocytes.
D. Neutrophils
E. Oligodendroglial cells
B.
Microglia
(extra info from slide)
In polio, the dying anterior motor neurons are surrounded by phagocytic microglial cells. This is termed neuronophagia.
The destruction of the anterior motor neurons by the viral infection leads to lower motor neuron signs (e.g. atrophy of the muscle).
A 40-year-old man with HIV develops an opportunistic viral infection of his brain following infection with the JC virus. A section of his brain is shown. The shown appearance is most likely due to infection of which cell type?
A. Astrocytes
B. Ependymal cells
C. Meningeal cells.
D. Microglia
E. Neurons
F. Oligodendroglial cells
F.
Oligodendroglial cells
(extra info from slide)
Progressive multifocal leukoencephalopathy (PML) results from infection of the oligodendroglial cells by the JC virus. This results in foci of demyelination.
The photo on the left is stained with Luxol Fast Blue. This section of white matter should normally stain all blue (i.e. myelinated). The areas that are not blue are foci of demyelination. The photograph on the right showed the oligodendroglial nuclei with viral inclusions; the nuclei appear enlarged and have empty-appearing areas.
