Download SDL 2- CNS Malformations Neural Tube Defects Failure of a portion

SDL 2- CNS Malformations
Neural Tube Defects
Failure of a portion of the neural tube to close completely or reopening
Abnormalities of meninges, neural tissue, ST bone
Encephalocele: malformed CNS tissue extending through defect in cranium (most common in posterior fossa)
1/1000 births in american Caucasians
Between 18-26 days
Primary neurulation: brain and SC are developed, neural folds form and converge toward midline, form neural tube
Neural fold proceeds rostrally and caudally and the ends of the tube remain open: neuropores
Closure of neural pores happens around day 26
Encephalocele: failure of rostral neural tube to close
Myelomeningocele: failure of caudal tube to close
Most common encountered neural tube closure defect
Spinal dysraphism: spina bifida cystic (myelomeningocele) and meningocele
Failure of ectoderm to separate properly from the neural ectoderm and persistence of neural placode (flat plate
of un-neurulated tissue)
More common in female
Risk factors: pregestational diabetes, inadequate maternal folic acid, in-utero exposure to anti-epileptic drugs
Congenital spinal meningoceles: vertebral defect with cystic lesion of herniated dura and arachnoid (SC normal);
1/1000
Most are lumbosacral
Increased CNS infection due to poor skin covering
Lower extremity sensory and motor function normal to paraplegia (above L3)
Chronic UTI, pyelonephritis
1/3 have apnea, swallowing difficulties, impaired head control, hydrocephalus
Meningocele: neurologically normal with no hydrocephalus, no CNS infection increase
Serum alpha-fetoprotein and prenatal ultrasound diagnosis
Confirmed with amniocentesis, MRI with T2 weighted sequences can provide structural information
Forebrain Anomalies
Abnormalities of brain volume
Megalencephaly: increased brain volume
Microencephaly: decreased brain volume
Most common; due to chromosomal abnormalities, fetal alcohol syndrome, HIV acquired in utero
Neurons and glial cells that form the cerebral cortex migrate to cortex guided by adhesion molecules, cortical
development entails the generatio of stem cells and their differentiation to neurons and glia, migration to cortex
and organization to functional layers.
1. Neurons fail to migrate from the ventricles (periventricular heterotopias) or halfway (subcortical band heterotopia)
2. Neurons reach cortex, but large numbers do not (no normal cortical layers are formed, leading to formation of
lissencephaly and cobblestoe cortex
3. Neurons may overshoot the cortex and end up in subarachnoid space
4. Late stage of migration and cortical migration is disrupted (polymicrogyri)
Abnormal migration causes an abnormal gyral pattern
Lissencephaly, cobblestone cortex and polymicrogyri are associated with psychomotor retardation and intractable
seizures
Most neuronal migration defects have some genetic basis; genotypes and phenotypes may overlap
Lissencephaly: sulci are absent except for sylvian fissure
Cortex is thick and consists of molecular and 3 neuronal layers
Complete loss of LIS1 gene located on chrom 17p13 that forms a complex for cell migration, cell division and
intracellular transport
Complete loss of LISS1 gene is fatal, deletion of one copy causes lissencephaly
SDL 2- CNS Malformations
Lesions of LIS1 gene cause Miller-Dieker syndrome that is a combo of lissencephaly with dysmorphic facial
features, visceral abnormalities and polydactyly
Posterior Fossa Anomalies
Aqueductal atresia and aqueductal stenosis: common causes of congenital hydrocephalus with Chiari type malformation
Aqueductal atresia: occurs in utero or postnatally by thrombus formation from interventricular bleeding, infection, or
other abnormalities that cause gliosis and obliterate the aqueduct
X linked aqueductal stenosis by mutations in L1CAM gene on chromosome Xq28 that codes cell adhesion molecule
Associated mental retardation, absence of cortical spinal tracts, agenesis of corpus callosum
Chiari Malformations
Type II: characterized by neural tube defects (usually lumbosacral meningomyelocele), abnormalities of posterior fossa
and craniocervical junction and hydrocephalus
Contents of posterior fossa reside in large foramen magnum (low insertion of tentorium and shallow posterior fossa)
Cerebellum and brainstem are crowded and displaced into upper cervical canal
Medulla elongated and may be folded dorsally, aqueduct and 4th ventricle are collapsed
Associated aqueductal atresia
Blocked CSF flow may lead to hydrocephalus (possible hydromyelia or syringomyelia)
Type I: mild variant of type II, volume of posterior fossa is reduced overcrowding and herniation of cerebellar tonsils
and dorsal cerebellum into spinal canal
May also have syringomyelia and hydrocephalus (no associated NTD)
Many patients are asymptomatic, other complain of dizziness, CN abnormalities and headache
Dandy-Walker Malformation
Complete or partial agenesis of the cerebellar vemis
Hemispheres are connected by thin membrane of neural tissue that forms the fourth ventricle roof
Obstruction of fluid from 4th ventricle; 4th ventricle thus enlarges and membrane that forms its roof balloons to
create a large posterior fossa cyst that pushes the tentorium superiorly  obstruction of
cerebrovascular fluid  hydrocephalus
Neuro defecits and agenesis of corpus callosum and neuronal migration abnormalities
Most are sporadic (there are rare familial cases associated with genetic abnormalities- trisomy 3, 9, 13, and 18)
Syringomyelia
Tubular formed cavity of SC that can affect cervical and upper thoracic segments
Located I central gray matter of SC and enlarges over time
Syrinx is lined by glial tissue and contains CSF-like fluid that accumulates and grows under pressure causing atrophy of
gray and white matter of SC
Symptoms show in 2nd to 3rd decades of life; patients may demonstrate dissociated anesthesia (segmental loss of pain
and temp sensation), denervation, atrophy of muscle and kyphoscoliosis
Pressure is relieved by shunting of syrinx fluid or laminectomy
Often associated with type I Chiari malformations
Multifactoral cause, may be seen both superiorly and inferior to SC tumors such as ependymoma, pyelocytic
astrocytomas, and hemanngioblastomas
SDL 2- CNS Malformations
Vascular Malformations
Developmental venous anomalies: AKA venous angiomas
Radially arranged configuration of medullary veins (caput medusae) separated by normal brain parenchyma
Usually supratentorial with a frontal lobe predominance
Commonly present with seizures, progressive neurologic deficits and hemorrhage
Most common autopsy series (2%); Benign
Headache is most common complaint; diagnosis is by cerebral angiography (CT and MRI may also be helpful)
Can be treated conservatively in majority of patients and headaches and seizures managed medically
Capillary telangiectasias: Small lesions most common in the pons, middle cerebellar peduncles and dentate nuclei
Multiple lesions are common and composed of small dilated capillaries with no smooth muscle or elastic fibers
May be associated with microhemorrhage and gliosis
Some associated with Osler0Weber-Rendu (hereditary hemorrhagic telangiectasia)
Benign, usually silent and found on neuroimaging studies or at autopsy (MRI helpful), nonoperable
Cavernous malformations: AKA cavernous angiomas/hemangiomas or cavernomas
May be sporadic or inherited in familial pattern
Characteristic mulberry appearance with engorged purplish clusters of vessels
Tissue may demonstrate gliosis and hemosiderin-laden macrophages due to previous hemorrhages
30-40 years, men and women
Symptomatic hemorrhage, seizures and progressive neurologic defecits may be associated
Least common autopsy series (0.4%); Greater tendency toward neurologic sequelae
Blood flow is limited, dx by angiography is difficult (MRI more helpful)
Progressive neurologic deficit, intractable epilepsy and recurrent hemorrhage are indications for surgical removal
Arteriovenous malformations:
Greater tendency toward neurologic sequelae