Malformation Flashcards
cephaly
meh
- 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.)
=intrinsic abnormality
=extrinsic force
= destructive force
Malformation
Deformation
Disruption
Path of normal devo in CNS
Induction –> Neural tube formation –> Regionalisation and specification –>Proliferation and migration –> Connection and selection
Neural tube –>Brain & Spinal cord Neural crest –> PNS & leptomeninges
when does this occur?
Neurulation: 3-4 weeks
Paired cerebral Hemispheres, LV, BG, Thalami, Optic Nerves/ chiasmCC, SP
what is this, when does this occur?
Prosencephalic: 2-3 months
Full complement of neurons in cerebral hemispheres : seen at
3-4 months; Neuronal proliferation
Formation from 4 layered embryonic cortex–>6 layered adult cortex
seen in:
3-5 months: Neuronal migration
Synaptogenesis–> programmed Cell death
then
Formation of myelin –> increased electrical conduction
Organization 5 to postanal
Myelination: birth to postanatal
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)
How does suclation in brain occur?
5 months: major fissures
7 months: secondary sulci
9 months: tertiary sulci
Pattern of cerebral myelination
POsterior frontal/parietal/occiput–>
frontal and temporal complete–>
cerebrum by end of 2nd year
Where do se wee most issues with cerebral architecture?
deeper elements usually disorganize
different genes have different effect on layers
Most common category of CNS malformations
Disturbance of formation of neuroectodermal and/or overlying mesodermal structures
Neural tube defects
Pathogeneis of neural tube defect
_______ of neural tube-primary failure of neuroectoderm or mesoderm
OR
Reopening or secondary rupture of ____
Failure of closure
closed tube
Spina bifida
Anencephaly
Encephalocele
neural tube defects all Primary defects of closure
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
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%)
- 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 )
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
- 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
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)
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.
Both meninges & spinal cord herniated through vertebral defect, usually broad-based
• Cyst (“cele”) often ruptures and skin covering absent
Myelomeningocele
Cord abnomaliteis seen in myelomeningocele adn location
- Variable cord abnormalities :Complete disorganization and flattening or Slight midline opening
- Most (75%) are lumbosacral
Sings and symptoms of myelomeningocele
- 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
Tissue mass is attached by_____
_____location: “nasal glioma”
Disorganization of remaining brain in cranial cavity
pedicle
Ethmoidal
Dx of Encephalocele
- 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
• 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
- 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:
- -Many small gyri fused together
- -Cortical ribbon is thin & excessively folded & fused –Two or four cortical layers
polymicrogyria
Cause of Agyria
- 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,
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:
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
- 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
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
