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2H. Pathology- CNS > Malformations & Developmental Diseases > Flashcards

Flashcards in Malformations & Developmental Diseases Deck (58)
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Although the pathogenesis and etiology of CNS malformations are largely unknown, both______________appear to be involved.


 Aberrations of signaling molecules
and mutations of homeotic genes that control body patterning are being increasingly identified
as causes of developmental disorders of the CNS. Many toxic compounds and infectious agents
are also known to have teratogenic effects

genetic and environmental influences 



  1. encephalocele
  2. Spinal dysraphism or spina
  3. Myelomeningocele (or meningomyelocele)
  4. Anencephaly


What is a Neural Tube Defect?6]

 Failure of a portion of the neural tube to close, or reopening of a region of the tube after
successful closure, may lead to one of several malformations.

Note :  All are characterized by
abnormalities involving some combination of neural tissue, meninges, and overlying bone or
soft tissues.


 What is an encephalocele?

An encephalocele is a diverticulum of malformed CNS tissue extending through a
defect in the cranium


Where does an encephalocoele mostly occurs?

It most often occurs in the occipital region or in the posterior fossa.


Collectively,_________________ account for most CNS malformations.

 neural tube defects


The most common neural tube defects involve the ____________ and are caused by a failure of
closure or by reopening of the caudal portions of the neural tube.

spinal cord


What is a spinal dysraphism or spina bifida?

It may be an asymptomatic bony defect (spina bifida occulta) or a severe malformation with
a flattened, disorganized segment of spinal cord, associated with an overlying meningeal


What is Myelomeningocele (or meningomyelocele)? . 

refers to extension of CNS tissue
through a defect in the vertebral column; the term meningocele applies when there is only a
meningeal extrusion


Myelomeningoceles occur most commonly in the____________, 

 lumbosacral region


affected individuals manifest clinical deficits referable to _____________________________-

motor and sensory function in the lower
extremities as well as disturbances of bowel and bladder control from both the structural
abnormality of the cord itself and superimposed infection that extends from the thin, overlying


The frequency of neural tube defects varies widely among different ethnic groups. Both ____________are involved. 

and environmental factors 


The concordance rate is high among _____________



the overall recurrence rate for a neural tube defect in subsequent pregnancies has
been estimated at __________. 

4% to 5%


____________ during the initial weeks of gestation has been
implicated as a risk factor; differences in rates of neural tube defects between populations can
be attributed in part to polymorphisms in enzymes of folic acid metabolism.


Folate deficiency


Folate deficiency
may affect cell division during critical periods that coincide with closure of the neural tube.
Antenatal diagnosis is based on______________

 imaging and the screening of maternal blood samples for
elevation of α-fetoprotein.


Anencephaly is a malformation of the____________. 

 anterior end of the neural tube, with absence of the brain
and calvarium


In anencephaly forebrain development is disrupted at approximately ________________days of gestation, and
all that remains in its place is the area cerebrovasculosa, a flattened remnant of disorganized
brain tissue with admixed ependyma, choroid plexus, and meningothelial cells. The posterior
fossa structures may be spared, depending on the extent of the skull deficit; descending tracts
associated with disrupted structures are, as expected, absent.



What is cerebrovasculosa?.

, a flattened remnant of disorganized
brain tissue with admixed ependyma, choroid plexus, and meningothelial cells. 



  1. (megalencephaly) or small (microencephaly)
  2. lissencephaly (agyria)
  3. Polymicrogyria
  4. Neuronal heterotopias
  5. Holoprosencephaly
  6. agenesis of the corpus callosum


The volume of brain may be abnormally large (megalencephaly) or small (microencephaly).
____________, by far the more common of the two, can occur in a wide range of settings,



Microencephaly, by far the more common of the two, can occur in a wide range of settings,
including :

  1. chromosome abnormalities,
  2. fetal alcohol syndrome,
  3. and human immunodeficiencyvirus 1 (HIV-1) infection acquired in utero.


What is the postulated theory behind microcephaly?

It is postulated that the underlying anomaly is a
reduction in the number of neurons that reach the neocortex and this leads to a simplification of
the gyral folding
—a model supported by experimental results in mouse models.


The pool of
proliferating precursor cells in the developing brain lies adjacent to the ventricular system.
Neuronal number is determined by the fraction of proliferating cells that undergo transition into migrating cells with each cell cycle. Early on, most cell divisions yield two more progenitor cells,
while as development progresses there are more asymmetric divisions yielding both a
progenitor cell and a cell headed for the developing cortex. If excess cells exit the proliferating
pool too early, then the overall generation of neurons is reduced; if too few exit during early
rounds of division, then the geometric expansion of the proliferating population results in an
eventual overproduction of neurons


Among the recognizable malformations [10] are conditions that can range from a noticeable
decrease in the number of gyri to total absence
, leaving a ________________( Fig. 28-5 ). 

smooth-surfaced brain,
lissencephaly (agyria) 


 A variety of forms of lissencephaly with distinct genetic
causes have been described. One of the best understood causes is mutations in the gene
encoding the _____________ which complexes with dynein and affects the
function of the centrosome
in nuclear movement.

microtubule-associated protein LIS-1,


Lissencephaly can also occur from a series of
mutations in the genes encoding enzymes responsible for the ______________;
when this receptor for extracellular matrix components does not have appropriate posttranslational
modifications, its stability is diminished

glycosylation of α-dystroglycan


Polymicrogyria is characterized by _______________.The gray matter is composed of four layers (or fewer), with entrapment of
apparent meningeal tissue at points of fusion that would otherwise be the cortical surface.

small, unusually numerous, and irregularly formed cerebral


Polymicrogyria can be induced by localized tissue injury toward the end of neuronal migration,
although genetically determined forms, which are typically bilateral and symmetric, are also


__________s are a group of migrational disorders that are commonly associated with
epilepsy. [12] 

Neuronal heterotopia


What are neuronal heterotopia?

They consist of collections of neurons in inappropriate locations along the
migrational pathways.