Anatomic pattern of malformation reflects ______at time of injury Prenatal or perinatal insults may cause failure of development and/or tissue destruction Contributing factors:

stage of brain formation Genetics Environment (toxins, vascular compromise, infections, etc.)

Malformation Flashcards by Meghan May

cephaly

meh

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Anatomic pattern of malformation reflects ______at time of injury
Prenatal or perinatal insults may cause failure of development and/or tissue destruction
Contributing factors:

stage of brain formation

Genetics
Environment (toxins, vascular compromise, infections, etc.)

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=intrinsic abnormality

=extrinsic force

= destructive force

Malformation

Deformation

Disruption

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Path of normal devo in CNS

 Induction –> Neural tube formation –> Regionalisation and specification –>Proliferation and migration –> Connection and selection

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Neural tube –>Brain & Spinal cord Neural crest –> PNS & leptomeninges

when does this occur?

Neurulation: 3-4 weeks

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Paired cerebral Hemispheres, LV, BG, Thalami, Optic Nerves/ chiasmCC, SP

what is this, when does this occur?

Prosencephalic: 2-3 months

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Full complement of neurons in cerebral hemispheres : seen at

3-4 months; Neuronal proliferation

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Formation from 4 layered embryonic cortex–>6 layered adult cortex

seen in:

3-5 months: Neuronal migration

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Synaptogenesis–> programmed Cell death

then

Formation of myelin –> increased electrical conduction

Organization 5 to postanal

Myelination: birth to postanatal

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Development of the Neural Tube & Axial Skeleton

Neural tube closure occurs early in _____
Closure occurs at several sites along neuraxis****-Failure of closure at these sites results in v

gestation (28 days)

arying types of defects (anencephaly, spina bifida)

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How does suclation in brain occur?

5 months: major fissures

7 months: secondary sulci

9 months: tertiary sulci

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Pattern of cerebral myelination

POsterior frontal/parietal/occiput–>

frontal and temporal complete–>

cerebrum by end of 2nd year

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Where do se wee most issues with cerebral architecture?

deeper elements usually disorganize

different genes have different effect on layers

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Most common category of CNS malformations
Disturbance of formation of neuroectodermal and/or overlying mesodermal structures

Neural tube defects

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Pathogeneis of neural tube defect

 _______ of neural tube-primary failure of neuroectoderm or mesoderm

 Reopening or secondary rupture of ____

Failure of closure

closed tube

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 Spina bifida

 Anencephaly

Encephalocele

neural tube defects all Primary defects of closure

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Failure of closure of the neural tube allows excretion of fetal substances such as ______ into the amniotic fluid.

Diagnosable by ultrasound and/or prenatal screening of maternal serum for _____ at 16-18 wks

Maternal periconceptional use of ____ supplementation reduces the incidence of NT defects by at least 50%

(AFP, acetylcholinesterase)

AFP at 16-18 week GA

folic acid

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What is spina bifida?

less severe forms?

Combined malformations of vertebral column & spinal cord
Spina bifida occulta – least severe form
Spina bifida cystica (80-90% lumbosacral)
Meningocele (less common – 10-20%)
Myelomeningocele (more common – 80-90%)

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Non-closed vertebral arches without visible lesion (externally)
Most often lumbosacral
Often asymptomatic

Oculta

(May be foot & gait abnormalities, In some, patches of hair, lipoma, discoloration of skin or dermal sinus may be present )

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Dx of Occulta

Spine x-ray: defect in closure of the ________, usually in L5 and S1
May be associated with syringomyelia, diastematomyelia, and tethered cord
Recurrent meningitis of occult origin should prompt careful exam for ____

posterior vertebral arches and laminae

dermal sinus tract

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Cyst lined with meninges & dura (but no spinal cord), herniated through vertebral defect
Spinal cord may be normal, or may present with tethering, syringomyelia, or diastematomyelia
Most are lumbosacral

Meningocele

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Symptoms of meningocele

Little or no neurologic deficit
Anterior meningocoele may project into the pelvis through a defect in the sacrum causing symptoms of constipation and bladder dysfunction
Female patients may have associated anomalies of the genital tract (rectovaginal fistula, vaginal septa)

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Dx and Tx of meningocele

• Diagnostic testing: plain x-ray, MRI for the spine, CT of the head to rule out HCP

Asymptomatic : with no neuro findings and full-thickness skin may have surgery delayed.
Patients with leaking CSF or a thin skin covering should undergo immediate repair to prevent meningitis.

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Both meninges & spinal cord herniated through vertebral defect, usually broad-based

• Cyst (“cele”) often ruptures and skin covering absent

Myelomeningocele

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Cord abnomaliteis seen in myelomeningocele adn location

* Variable cord abnormalities :Complete disorganization and flattening or Slight midline opening * Most (75%) ar**e lumbosacral**

Sings and symptoms of myelomeningocele ## Footnote

* CM: flaccid paralysis, absent DTRs, sensory deficit below the affected level, postural abn of the LE (clubfeet, subluxation of the hips), constant urinary dribbling and a relaxed anal sphincter * Weakness or flaccid paralysis, sensory loss, bowel/bladder dysfunction

Complicationos myelomeningocoele

Complications: meningitis, hydrocephalus, pneumonia

We can see this issue in pts that have hydrocephalus and myelomeningocole

Type II chiaria defects

symptoms of hindbrain dysfunction: difficulty feeding, choking, stridor, apnea, VC paralysis, pooling of secretions, spasticity of UEs

Infants with HCP and Chiari II

is due to downward herniation of the medulla and cerebellar tonsils

Chiari crisis

Tx for myelomingocoele

* Requires a multidisciplinary approach: surgeon, therapist, pediatrician * Surgery: repair and shunting; orthopedic procedure, urologic evaluation * GUT: regular catheterization to prevent UTI and reflux leading to PN and hydronephrosis, urine cult, serum elec, creatinine, renal scan, IV pyelogram, Utz * Rehab: functional ambulation (sacral or LS lesion

Prognosis for myelomeningocoele

* MR- 10-15% * Most deaths occur before age 4 years * 70% have normal intelligence, but learning problems and seizure disorders are common * History of meningitis or ventriculitis adversely affect the ultimate IQ

Large defect of the calvarium, meninges, and scalp associated with a rudimentary brain which results from failure of closure of the rostral neuropore

Anecephaly

Dx anecephaly

Diagnosed by increased AFP in amniotic fluid Primitive brain consists of portions of connective tissue, vessels and neuroglia Cerebral and cerebellar hemispheres are usually absent, and only a residue of the brainstem can be identified **(Eyes and cranial nerves V-XII intact) **

Anecephaly is large defect of the calvarium, meninges, and scalp associated with a rudimentary brain which results from failure of closure of the

rostral neuropore

Broad-based pedunculated masses of **cerebral tissue & dura** protruding through cranial defect, covered by skin **Occipital** region is most common site, although frontal/nasal locations are more common in some countries

Encephalocele

Encephalocele: Definition Broad-based pedunculated masses of ____ and ____ protruding through cranial defect, covered by skin \_\_\_\_region is most common site, although frontal/nasal locations are more common in some countries

cerebral tissue & dura Occipital

Encephalocele ## Footnote Tissue mass is attached by\_\_\_\_\_ \_\_\_\_\_location: “nasal glioma” Disorganization of remaining brain in cranial cavity

pedicle Ethmoidal

Dx of Encephalocele ## Footnote

* Diagnosis: * Plain x-ray of the skull and cervical spine * Cranial utz * In utero: AFP, biparietal diamete

AR condition, occipital encephalocoele, cleft lip or palate, microcephaly, microphthalmia, abnormal genitalia, polycystic kidneys, and polydactyly

Meckel-Gruber syndrome: spectrum of encephalocele

Forebrain anomalies ## Footnote • Disorders of _____ and \_\_\_\_\_\_ * Polymicrogyria * Agyria and Pachygyria * Disorders of\_\_\_\_\_\_ of forebrain * Arrhinencephaly: Holoprosencephaly • Olfactoryaplasia Agenesis of corpus callosum

migration and sulcation cleavage

* Polymicrogyria (too many foldso) * Agyria (lissencephaly) and pachygyria (too few folds)

Forebrain shit from migraiton and sulcation

Patho of migration/sulcation issues of forebrain ## Footnote * Disturbance of process of neuronal migration from _____ to \_\_\_\_\_\_ * \_\_\_\_\_\_ is induced by presence of normally migrated neuronal population

germinal matrix to cortex Sulcation

Too many irregular small fused gyri that Results from disordered organization of the neurons in the cortex at the time of migration • Neuriteextension,synaptogenesis,&maturation

POlymicrogyria

Cuase of polymicrogyria

GRoss pathology: ## Footnote - -Many small gyri fused together - -Cortical ribbon is thin & excessively folded & fused --Two or four cortical layers

polymicrogyria

Cause of Agyria ## Footnote * Neurons migrate only part way to cortex, so gyri don’t form correctly (or at all), occurs around the \_\_\_\_\_of gestation * Several genetic types: association with mutations on ___ and \_\_\_

4th month chr 17 and X chromosome

Agyira, ## Footnote Seizures, mental retardation, lissencephaly * Deletion in LIS1 gene on chr. 17 * prominent forehead, bitemporal hollowing, anteverted nostrils, prominent upper lip, micrognathia • (90% with chromosomal deletions of 17p13.3- lissencephaly I gene)

Miller Dieker syndrome

Clinical S/S in pts with agyria and pachgyria

* failure to thrive• Microcephaly • marked developmental delay • severe seizure disorder * hypoplasia of the optic nerve • microphthalmia

Sometimes the pattern of agyria allows prediction of \_\_\_\_\_ Females with \_\_\_\_have imaging abnormalities distinct from other agyrias

the causative gene DCX mutation

Thickened cortical ribbon consists of four layers

pachygyria

* Unilateral or bilateral clefts within the cerebral hemispheres due to an abnormality of **morphogenesis** * The cleft may be fused or unfused, and is usually surrounded by abnormal brain, microgyria

Schizencephaly

Present with severe MR, intractable Szs, microcephaly, spastic quadriplegia when clefts are bilateral

Schizencephaly

* Absence of olfactory tract/bulbs * But usually much more missing than the olfactory brain.... * Holoprosencephaly and olfactory aplasia

Arrhinencephaly: forebrain cleavage defect

Severity of craniofacial defect mirrors severity of underlying brain abnormality * “The face predicts the brain” * Cyclopia - most severe * Hypotelorism – minimal chang

arrhinecephaly or forebrain cleavage defects

Forebrain cleavage defect path: ## Footnote Attributed to absent cleavage of forebrain, during the ____ to\_\_\_\_week of gestation Usually sporadic and Autosomal dominant form associated with mutation in : Also associated with **Trisomies** Association with **EtOH**, **Accutane** (retinoic acid) during pregnancy & diabetes

4th to 6th Sonic Hedgehog gene (SHH) on 7q26

• Incomplete separation of hemispheres

Holoprosencephaly

Small brain Cerebral hemispheres fused into single mass with no interhemispheric fissure: single large ventricle Hypoplasiaofcortex

Alobar holoprosencephaly

\_\_\_\_\_\_ holoprosencephaly = Partial formation of interhemispheric fissure •\_\_\_\_\_ holoprosencephaly = Midline continuity of cortex at frontal pole with almost normal brain size - often associated with craniofacial anomalies

Semilobar (on 1st page) Lobar

Clinical S/S holoprocephaly

• Clinically, present with profound MR, seizures, rigidity, apnea and temperature imbalance; HCP can develop with aqueductal obstruction; endocrine disorders can present with hypothalamic or pituitary malformations

Facial abnormalities include cyclopia, cebocephaly, and premaxillary agenesis

Holy-hell-procephaly

Dx for holoproencephaly

Diagnostic testing: facial x-ray to show deformed anterior craniobasal bones, cytogenetics, MRI. EEG, VER, ABR are generally abnormal.

Agenesis of Corpus callosum * Results from an insult to the \_\_\_\_\_\_during embryogenesis * No corpus callosum or cingulate gyrus thus gyri extendd\_\_\_\_\_ to 3rd ventricle roof \_\_\_\_\_\_ - stumps of white matter at edge of cortex

commissural plate perpendicular

Symptoms or association of no corups callosum

associated migration defects (heterotopia, microgyria, pachygyria) may present with MR, microcephaly, hemiparesis, diplegia and seizures May be Frequently found in assoc. with other malformations • Aicardi syndrome – X-linked, chorioretinal defects, seizures

imaging for agenesis of Corpus callosum

Widely separated frontal horns with an abnormally high position of the 3rd ventricle

Patients are almost all females (may be lethal in males) Characterized by severe MR, intractable seizures with onset between birth and 4 months of age, and chorioretinal lacunae. Hemivertebrae and costovertebral anomalies are common.

Aicardi Syndrome EEG: independent activity from both hemispheres as a result of the absence of the CC

• Associated with: • Hydrocephalus * Sudden death * May haveneurologic signs/symptoms * Cranial nerve palsies • Ataxia • Long tract signs * May be asymptomatic

• Type 1 – chronic tonsillar herniation

Type I Chiari malformations ## Footnote * 90% also have: * No known genetic or associated risk factors at present

syringomyelia

What does Type I Chiari look like on MRI

chronic tonsillar malformation

Herniated cerebellar tissue through foramen magnum with displacement of dorsal medulla causing a hump or Z-shape in brainstem/spinal cord • Associated with lumbar myelomeningocele

Type 2 Chiari Malformation (Arnold-Chiari malformation)

(Chiari 2 is present in \>95% of children with\_\_\_\_\_\_\_)

myelomeningocele

• Lower cranial nerve defects (swallowing, respiration) * Arm weakness, spasticity * S/S referable to hydrocephalus

Type 2 Chiari or Arnold chiari

Etiology for Type II arnold-Chiaria malformation

Vitamin A deficiency (maternal) associated with Chiari II & myelomeningocele No genetic associations yet found Pathogenesis (hypothesis): Disproportion between growth of posterior fossa & its contents (posterior fossa too small) causes kinking of medulla & “squashing” of cerebellum into spinal canal

Disproportion between growth of posterior fossa & its contents (posterior fossa too small) causes kinking of medulla & “squashing” of cerebellum into spinal canal

Type 2 Chiari Malformation (Arnold-Chiari malformation)

• Agenesis of vermis (Key Feature) Cystic dilatation of 4th ventricle Enlargement of posterior fossa Hydrocephalus is frequently present

Dandy Walker malformation

Risk factors associated findings etiology of Dandy Walker

* Associated with motor retardation, spasticity, and respiratory failure * Risk factors: Isotretinoin use during pregnancy * Etiology:• Most cases are sporadic • Assoc.w/trisomies

Fluid filled cleft-like cavity in spinal cord * Cavity extends transversely cross cord crossing behind the central canal * Usually largest in cervical regions

Syringomyelia

* Association with Chiari type 1 malf.(90%) * Also seen post trauma and in assoc. with spinal cord tumors

syringomyelia

Loss of pain/temperature, retention of position and vibration senses & motor function. Onset of symptoms in 2nd/3rd decades; progressive see fluid filled cleft like cavity in spinal cord

Syringomyelia

Perinatal Hypoxic/Ischemic & Hemorrhagic Lesions : Hypoxia/ischemia • _____ matter: White matter\_\_\_\_\_ (periventricular leukomalacia) • Both gray & white matter: \_\_\_\_\_\_

White necrosis Multicystic encephalopathy

Symptoms of Perinatal Insults: Cerebral Palsy * \_\_\_\_\_\_\_neurologic motor deficit • Spasticity, dystonia, ataxia/athetosis, paresis * Attributed to insults occurring in the ____ and \_\_\_\_\_\_ * Wide range of neuropathologic findings * Often hypoxic/ischemic or hemorrhagic events

Non-progressive fetal and perinatal periods

• Sharply defined foci of necrosis in WM * Gross discrete chalky yellow plaques * May eventually cavitate

White matter necrosis: Periventricular leukomalacia

Who do we see Periventricular leukomalacia in

* Common in premature infants with ischemia/hypoxia * Also occurs in full-term infants with cardiac or pulmonary disease

Pathogenesis of pervientricular leukomalacia

• Selectively vulnerable oligodendrocytes * Impaired perfusion of boundary zone * Poor cerebral vascular autoregulation

What do we see on histo in periventricluar leukomalacia?

* Central zone of necrosis * Surrounding mineralization axon

• Destruction of both gray and white matter in 3rd trimester * Sponge-like glial lined cysts remain * Attributed to extensive hypoxia/ischemia

multicycstic encephalopathy

* Originate in periventricular germinal matrix * Most frequently in germinal zone overlying head of caudate and thalamus * Frequently break through into ventricular system or underlying parenchyma

Subependymal Germinal Matrix Hemorrhages

Causes for Subependymal Germinal Matrix Hemorrhages

• Onset related to extreme physical distress (most often in the context of prematurity) * Perinatal occurrence * Hemodynamic instability * Mechanical ventilation * Hyaline membrane disease

Grading for subependymal hemorrhages ## Footnote Grade 1 – Confined to \_\_\_\_ Grade 2 – Germinal matrix & lateral ventricle, no \_\_\_\_\_ Grade 3 - Germinal matrix & lateral ventricle, with \_\_\_\_\_\_ Grade 4 – As above with extension into \_\_\_\_\_

germinal matrix ventricular dilatation cute ventricular distention adjacent brain parenchyma

Malformation Flashcards

(89 cards)