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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.


As might be expected, one location in which heterotopias can be found is
along the_______—as though the cells never managed to leave their place of birth.

 ventricular surface


______________ can be caused by mutations in the gene encoding filamin A

Periventricular heterotopias


What is filamin A?

 an actin-binding protein responsible for assembly of complex meshworks of filaments.

This gene is
on the X chromosome, and the mutant allele causes male lethality; in females the process of X
inactivation separates neurons into those with a normal allele (in the correct location) and those
with the mutant allele (in the heterotopia). 


Another microtubule-associated protein, ____________ is also encoded by a gene on the X chromosome; mutations in this gene result in
lissencephaly in males and in subcortical band heterotopias in females. 



These heterotopias
may consist of 

discrete nodules of neurons sitting in the subcortical white matter or complete
ribbons that parody the overlying cortex


_______________is a spectrum of malformations characterized by incomplete separation of
the cerebral hemispheres across the midline. 



Severe forms of holosencephaly manifest __________________; 

midline facial
abnormalities, including cyclopia


less severe variants (arrhinencephaly) show _____________. 

absence of the
olfactory cranial nerves and related structures


Intrauterine diagnosis of severe forms by
____________ examination is now possible. 



Holoprosencephaly is associated with _________ as
well as other genetic syndromes. [13] 

trisomy 13


___________ is a member of a family of secreted
proteins synthesized by the notochord
and neural plate during neural development

Sonic hedgehog 


affecting sonic hedgehog or its signaling pathway may result in holoprosencephaly


In agenesis of the corpus callosum, a relatively common malformation, there is an________________ ( Fig.
28-6 ). 

 absence of
the white matter bundles that carry cortical projections from one hemisphere to the other


agenesis of the corpus callosum, a Radiologic imaging studies show _____________ on
coronal whole-mount sections of the brain, bundles of anteroposteriorly oriented white matter
can be demonstrated.

misshapen lateral ventricles (“bat-wing” deformity);


 Agenesis of the corpus callosum can be associated with mental
retardation or may occur in clinically normal individuals.

It can be present in isolation or can be
associated with a wide range of other malformations

Unlike patients with surgical callosal
section, who show clinical evidence of hemispheric disconnection, individuals with this
malformation can have minimal deficits.



  1. Dandy-Walker malformation
  2. Arnold-Chiari malformation (Chiari type II malformation)


The Dandy-Walker malformation is characterized by_________________

  •  an enlarged posterior fossa.
  • The cerebellar vermis is absent or present only in rudimentary form in its anterior portion.
  • In its place is a large midline cyst that is lined by ependyma and is contiguous with leptomeninges on its outer surface.
  • This cyst represents the expanded, roofless fourth ventricle in the absence of a normally formed vermis. 


What are commonly found in association with Dandy-Walker malformation.

Dysplasias of brainstem nuclei


Arnold-Chiari malformation (Chiari type II malformation) consists of a

  •  small posterior fossa,
  • a misshapen midline cerebellum with downward extension of vermis through the foramen magnum ( Fig. 28-7 ), and,
  • almost invariably, hydrocephalus and a lumbar myelomeningocele.


What are oher associated changes Arnold-Chiari malformation (Chiari type II malformation) may include ____________________


  • caudal displacement of the medulla,
  • malformation of the tectum,
  • aqueductal stenosis,
  • cerebral heterotopias,
  • and hydromyelia (see later).


 In the Chiari I
, ____________

. In contrast to the
significant clinical consequences of the preceding two malformations, this may be a silent
abnormality or may cause symptoms referable to obstruction of CSF flow and medullary
compression; if present, these symptoms can usually be corrected by neurosurgical

low-lying cerebellar tonsils extend down into the vertebral canal


What is Hydromyelia? 

These are disorders characterized by a discontinuous multisegmental or confluent expansion of
the ependyma-lined central canal of the cord (hydromyelia)


What is syringo syringobulmyelia or syringobulbia?

 by the formation of a fluid-filled
cleftlike cavity in the inner portion of the cord (syringomyelia, syrinx) that may extend into the
brainstem (syringobulbia).


Syringomyelia may be associated with the____________; it may also occur in association

  •  Chiari I malformation
  •   intraspinal tumors or following traumatic injury


  In general, what is the histologic appearance in  SYRINGOMYELIA AND HYDROMYELIA

similar in all these conditions, with destruction of the adjacent gray and white matter,
surrounded by a dense feltwork of reactive gliosis.


SYRINGOMYELIA AND HYDROMYELIA what age of manifestation?

 The disease generally becomes manifest in
the second or third decade of life


What are the distinctive symptoms and signs of a syrinx 

isolated loss of pain and temperature sensation in the upper extremities because of the
predilection for early involvement of the crossing anterior spinal commissural fibers of the spinal


What is the reason for the isolated cause of manifestation in signs of a syrinx

because of the
predilection for early involvement of the crossing anterior spinal commissural fibers of the spinal