Pediatrics Flashcards
Germinal Matrix hemorrhage
Spontaneous hemorrhage in premature infants between 22-30 weeks gestation, usually weighing <1500g. The most common site is the germinal matrix at the median eminence (covering the basal ganglia). The most common site is the periventricular matrix zone located between the caudate nucleus and thalamus at the level of or slightly posterior to the foramina of Monro. The next common site is the occipital lobe. The least common site is the temporal horn of lateral ventricle.
Etiology: By the 18th to 20th week of gestation, the neocortical ventricular wall is lined by a prominent hypercellular well-vascularized zone known as the germinal matrix. This germinal zone is composed of undifferentiated, differentiating and migrating cells, radial glial fibers, polymorphous astrocytes, and thin-walled blood vessels. The germinal cells have very little structural support and the vessels are very fragile. A lot of angiogenesis and vessel remodeling is going on during this period and this may be the reason why this area is so susceptible to hemorrhage in younger premature infants. The control of blood pressure in the brain is not well developed in these infants. The hemorrhage is usually resulted of damage of the vessel wall. The mechanism may be damage of the endothelial cells by acidosis secondary to hypoxia. Birth injury seems to play a role as one-third of cases have difficult deliveries due to forceps rotations and breech presentation.
Germinal matrix with subependymal hemorrhage only
Papile’s classification Grade I
Germinal matrix hemorrhage with rupture into the ventricle
Papile’s classification Grade II
Germinal matrix hemorrhage with intraventricular hemorrhage and ventricular dilation
Papile’s classification Grade III
Germinal matrix hemorrhage with intraventricular hemorrhage with ventricular dilation and parenchymal extension
Papile’s classification Grade IV
Chiari type I malformation
tonsil is herniated into the upper cervical cord. There is no obvious deformation of the pons and brainstem. The cerebellar vermis does not appear to be malformed.
Chiari type II malformation
haracterized by displacement of the cerebellar vermis combined with deformities of the medulla and tectal plate with the later one leading to the tectum adopting the shape of a bird’s beak (so-called “beaking of the tectum”). It is often associated with syringomyelia, hydromyelia, spinal bifida, meningocele or meningomyelocele, and hydrocephalus. It can also associate with other malformations of the brain, cranium and meninges, cardiovascular, gastrointestinal and genitourinary systems. Chiari type II malformation is probably secondary to a neural tube defect. Chiar II malformations are typically associated neural tube defects such as meningomyelocele.
Chiari III malformation
encephalocele formed by herniation of the structures of the posterior fossa, including the cerebellum, through an occipitocervical or high cervical bony defect. There may also be beaking of of the tectum, elongation and kinging of the brainstem and lumbar spina bifida.
Dandy-Walker Syndrome
Syndromic malformation of the cerebellum and posterior fossa. The three essential features include:
-complete or partial agenesis of the vermis
-cystic dilatation of the fourth ventricle
-enlargement of the posterior fossa
Other common findings include:
-elevation of the tentorium cerebelli and lateral, transverse sinuses and torcula (torcular Herophilli)
-lack of patency of the foramina of Magendie and Luschka.
-Hydrocephalus
Other cerebral and visceral anomalies are present. It is the presence or absence of other cerebral and visceral abnormalities that determines the prognosis of individuals. About 68% of all cases have other developmental abnormalities of the CNS. Facial abnormalities may also be seen.
Caudal regression syndrome
mermaid syndrome comprises a variable defect of lumbar vertebrae, sacrum, and coccyx. This is a severe developmental field defect of the posterior axis caudal blastema. The severest form is sirenomelia (mermaid syndrome). It is frequently associated with abnormalities of the anorectal and urogenital systems and lower limbs. The entire urinary tract can be absent. The pathogenesis is probably related to the failure of growth of the caudal eminence. The strongest association of caudal regression is with maternal diabetes, it has also been related to deletion of chromosome 7q, autosomal dominant and, probably, autosomal recessive transmission. Timing: it occurs in the primitive streak stage during week 3 of gestation before development of the allantois, and the allantoic vessels are usually absent. There is a single umbilical artery that arises directly from the aorta.
Agenesis of corpus callosum
primary deficiency of axons of the corpus callosum cross the midline in the usual position are absent or deficient. Critical event(s) must have happened no later than 9th to 20th week of gestation, the peak time of development of corpus callosum. The corpus callosum develops in an anterior to posterior fashion, partial agenesis usually involves the posterior part while complete agenesis involves both anterior and posterior portions. If the anterior part of the corpus callosum is absent but the posterior part is present, a destructive mechanism should be seriously considered. Complete or partial agenesis of the corpus callosum rarely exists as an isolated entity. The cingulate gyrus overlying the residual portion of the corpus callosum has normal development. The more occipital portion of the cingulate gyrus, however, has vertical arrangement and is abnormal. Abnormal configuration of the cingulate gyrus is a constant association with agenesis of corpus callosum. In this particular case, Probst bundle, also called longitudinal corpora callosa. They are abnormal prominent bundle of fibers in median sagittal directions (longitudinal callosal fibers) in the lateral part of the roof of the lateral ventricles in cases of agenesis of corpus callosum. The volume of Probst bundle is significantly smaller than that of the corpus callosum.
Colloid cyst
Most commonly found in the third ventricle
Nodular heterotopia
Common, Heterotopic grey matter can be seen in anywhere within the brain but the ventricular surface is the most common site. There is a female predominance. It may consist of a single nodule of gray matter at the ventricular surface or a row of nodules at the ventricular wall creating an irregular ventricular surface. They are well demarcated from the underlying white matter. Bilateral ventricular nodular heterotopia is also associated with mutaion of filamin 1 gene on chromosome Xq28.
Periventricular leukomalacia
PVL is often seen in premature babies and occurs most commonly in those that are born at or after 30 weeks of gestation. It is resulted from increased susceptibility of the white matter to hypoxic ischemic injury due to the inherent high metabolic rate of white matter during this stage of development. For premature babies that are born with more prematurity, such as those born with less than 28 weeks of gestation, germinal matrix hemorrhage is far more common than PVL. PVL occurs as a well demarcated, small, irregular lesion, sometime with cavity formation, in the white matter at a short distance from the ventricle. The affected brain tissue is often mineralized and gives the chalky appearance, but they can be very subtle and minute
Alobar holoprosencephaly
On the frontal view, the two cerebral hemispheres appear to be fused in the midline although there is a falx like structure at the midline. In contrast, the cerebellum and the medulla seems to have split well into the right and left half. The cerebral hemispheres shows that the occipital portion is reduced to a thin translucent seam. The occipital portion of the parietal and occipital pallium is entirely converted into a thin membrane. The thalamus and the basal ganglia appear to have split into the left and right half. There is a single, dilated ventricle with no septum pellucidum.
De Morsier Syndrome (Septo-optic dysplasia)
characterized by optic nerve hypoplasia, aplasia or defects of the septum pellucidum (an inconstant finding), and pituitary-hypothalamic dysfunction (hypopituitarism). Two of the three features must be present to fulfill the diagnostic criteria and only a minor portion of cases have all three features. The floor of third ventricle, a structure embryonically related to the development of the optic placodes, is abnormal in some cases. Olfactory aplasia is frequent. Other features include elevation of the tentorium cerebelli and lateral and transverse sinuses and torcula, lack of patency of the foramina of Magendie and Luschka, and hydrocephalus. Not all these features are present in every case. Although the septum pellucidum can be missing to suggest holoprosencephaly, the brain clearly splits normally into the left and right hemisphere.
Leukodystrophy
white matter would lose its opaque white appearance and appears more translucent due to loss of myelin.
32 week brain fetus
Fetus at 32 weeks of gestation has very little, if any, myelin in the cerebral hemisphere
1 year old infant
brain is largely myelinated
Thalamic gliosis
Bilateral thalami become white and rubbery with extension to the surrounding white matter. Bilateral thalamic gliosis is not a rare finding at autopsy. Thalamic neurons are vulnerable for hypoxic-ischemic insults in the premature and term newborn. They are also vulnerable to damage in utero when the mother sustains a cardiorespiratory or hypotensive event during pregnancy. Characterized by atrophy, firmness, and a chalky-white appearance. The rubbery firmness is due to gliosis.
X-linked adrenal cortical leukodystrophy (X-ALD)
Disorder of peroxisomal fatty acid beta oxidation resulting in the build up of very long chain fatty acids (VLCFAs) within the body. This accumulation results in demyelination with macrophage infiltration and adrenal insufficiency. There is substantial loss of myelin in the cortical spinal tract but the myelination in the anterior spinal tract is relatively well preserved. This pattern is non-specific.
The adrenal glands are usually small and atrophic. Histologically, the zona glomerulosa is preserved but the cells in zona fasiculata and reticulata are enlarged, secondary to the accumulation of cytoplasmic birefringent striation. Lamellar cytoplasmic inclusions may be seen in the cells of the adrenal cortex.
Lipid lamellae: The lipid storage material stain poorly with traditional lipid stains. Under EM, the adrenal striations contain lamellae and lamellar lipid profiles. These lamellae are non-specific for X-ALD since they are also seen in other peroximal disorders including Zellweger syndrome, neonatal ALD, and infantile Refsum’s disease. These lipid droplets are seen in the cytoplasm of Schwann cells, testicular interstitial cells, liver, CNS macrophages, and oligodendrocytes.
Globoid cell leukodystrophy (Krabbe disease)
A sphingolipidosis with an autosomal recessive inheritance pattern. It is caused by mutation of the GALC gene (14q31) which results in deficiency of the galactosylceramidase enzyme (lysosomal galactocerebroside b-galactosidase). Asymptomatic at birth, affected patients begin to develop symptoms within the first few months of life including irritability, stiffness, and delayed motor development. Accumulation of galactosylceramide in macrophages of the brain results in enlarged, multinucleated, globoid cells. White matter damage (leukodystrophy) occurs secondary to myelin degeneration and oligodendrocyte loss.Both peripheral and central nervous systems are involved. Infantile onset is most common but later or adult onset cases have also been described. Clinically features vary with the age of onset. The infantile form is associated with death at 1-2 years of age. Pathologically, the brain is markedly atrophic and shows extensive demyelination associated with large, multinucleated cells (globoid cells). The white matter but not grey matter is predominantly affected. Crystalline needle-like inclusions that correspond to the globoid material are seen under electron microscope. There is no globoid cells here to qualify even a suspicion of this diagnosis.
Pelizaeus-Merzbacher disease
X-linked leukodystrophy caused by abnormalities of the proteolipid protein 1 (PLP1) gene (Xq22.2). Alteration of this gene results in hypomyelination and loss of oligodendrocytes with a characteristic sparing of the subcortical fibers. The peripheral nervous system is not affected.
Alexander disease
leukodystrophy caused by a mutation of the GFAP gene (17q21). Microscopic changes include loss of myelin and marked formation of Rosenthal fibers, particularly in a perivascular and subpial distribution.
