Malformations & Developmental Diseases

Question 1

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

Answer 1

both
genetic and environmental influences

Question 2

NEURAL TUBE DEFECTS

Answer 2

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

Question 3

What is a Neural Tube Defect?6]

Answer 3

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.

Question 4

What is an encephalocele?

Answer 4

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

Question 5

Where does an encephalocoele mostly occurs?

Answer 5

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

Question 6

Collectively,_________________ account for most CNS malformations.

Answer 6

neural tube defects

Question 7

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.

Answer 7

spinal cord

Question 8

What is a spinal dysraphism or spina bifida?

Answer 8

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
• *outpouching.**

Question 9

What is Myelomeningocele (or meningomyelocele)? .

Answer 9

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

Question 10

Myelomeningoceles occur most commonly in the____________,

Answer 10

lumbosacral region

Question 11

Myelomeningoceles
affected individuals manifest clinical deficits referable to _____________________________-

Answer 11

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
skin.

Question 12

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

Answer 12

genetic
and environmental factors

Question 13

The concordance rate is high among _____________,

Answer 13

monozygotic
twins

Question 14

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

Answer 14

4% to 5%

Question 15

____________ 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.

Answer 15

Folate deficiency

Question 16

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

Answer 16

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

Question 17

Anencephaly is a malformation of the____________.

Answer 17

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

Question 18

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.

Answer 18

28

Question 19

What is cerebrovasculosa?.

Answer 19

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

Question 20

FOREBRAIN ANOMALIES

Answer 20

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

Question 21

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,

Answer 21

Microencephaly

Question 22

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

Answer 22

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

Question 23

What is the postulated theory behind microcephaly?

Answer 23

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

Question 24

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 ).

Answer 24

smooth-surfaced brain,
lissencephaly (agyria)

Question 25

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 _____________ whic**h complexes with dynein and affects the function of the centrosome**in**nuclear movement.**

Answer 25

microtubule-associated protein LIS-1,

Question 26

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

Answer 26

glycosylation of α-dystroglycan

Question 27

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.

Answer 27

small, unusually numerous, and irregularly formed cerebral convolution

Question 28

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

Question 29

\_\_\_\_\_\_\_\_\_\_s are a group of migrational disorders that are commonly associated with epilepsy. [12]

Answer 29

Neuronal heterotopia

Question 30

What are neuronal heterotopia?

Answer 30

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

Question 31

As might be expected, **one location in which heterotopia**s can be found is along the\_\_\_\_\_\_\_—as **though the cells never managed to leave their place of birth.**

Answer 31

ventricular surface

Question 32

\_\_\_\_\_\_\_\_\_\_\_\_\_\_ can be caused by mutations in the gene encoding** filamin A**

Answer 32

Periventricular heterotopias

Question 33

What is filamin A?

Answer 33

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).

Question 34

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 heterotopia**s in **females.**

Answer 34

doublecortin (DCX),

Question 35

These heterotopias may consist of

Answer 35

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

Question 36

\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_is a spectrum of malformations characterized by **incomplete separation of** the **cerebral hemispheres** across the midline.

Answer 36

Holoprosencephaly

Question 37

Severe forms of holosencephaly manifest \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_;

Answer 37

midline facial abnormalities, including cyclopia

Question 38

less severe variants (**arrhinencephaly**) show \_\_\_\_\_\_\_\_\_\_\_\_\_.

Answer 38

absence of the olfactory cranial nerves and related structures

Question 39

Intrauterine diagnosis of severe forms by \_\_\_\_\_\_\_\_\_\_\_\_ examination is now possible.

Answer 39

ultrasound

Question 40

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

Answer 40

trisomy 13

Question 41

\_\_\_\_\_\_\_\_\_\_\_ is a member of a family of **secreted proteins synthesized by the notochord**and**neural plate**during**neural development**.

Answer 41

Sonic hedgehog Mutations affecting sonic hedgehog or its signaling pathway may result in **holoprosencephaly**

Question 42

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

Answer 42

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

Question 43

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.

Answer 43

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

Question 44

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.

Question 45

POSTERIOR FOSSA ANOMALIES

Answer 45

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

Question 46

The Dandy-Walker malformation is characterized by\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_

Answer 46

* 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.

Question 47

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

Answer 47

Dysplasias of brainstem nuclei

Question 48

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

Answer 48

* ** 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.

Question 49

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

Answer 49

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

Question 50

In the **Chiari I malformation**, \_\_\_\_\_\_\_\_\_\_\_\_ . 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 intervention.**

Answer 50

low-lying cerebellar tonsils extend down into the vertebral canal

Question 51

What is Hydromyelia?

Answer 51

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

Question 52

What is syringo syringobulmyelia or syringobulbia?

Answer 52

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).

Question 53

Syringomyelia may be associated with the\_\_\_\_\_\_\_\_\_\_\_\_; it may also occur in association with\_\_\_\_\_\_\_\_\_\_\_\_\_.

Answer 53

* Chiari I malformation * intraspinal tumors or following traumatic injury

Question 54

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

Answer 54

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

Question 55

SYRINGOMYELIA AND HYDROMYELIA what age of manifestation?

Answer 55

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

Question 56

What are the distinctive symptoms and signs of a syrinx

Answer 56

* *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 cord. **

Question 57

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

Answer 57

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