I am posting Eric Adelman’s slides which were much better than mine. CNS Malformations Ben Bly 2013 I am posting Eric Adelman’s slides which were much better than mine.

Cavum Septum Pellucidum Normal finding

Arachnoid Cysts Pocket of fluid within arachnoid Walls are arachnoid membrane Occur close to cisterns, often near sylvian fissure Do not communicate with CSF spaces Present in 0.5% at autopsy

Arachnoid Cysts Clinical Findings Treatment Asymptomatic Global disturbances Headache, signs/symptoms of increased ICP, enlarged HC, seizures, developmental delay Focal neurologic symptoms related to location Treatment If symptomatic: surgical decompression, shunt

Arachnoid cyst

Porencephaly Porencephalic cysts = cavity within brain parenchyma Injury during development Infarct / trauma Or faulty induction and neuronal migration Smooth walls, radially oriented gyri May be in distribution of a cerebral artery May or may not communicate with ventricle May require shunting if enlarging or progressive RITE 2008: question 318

Porencephaly

Hydranencephaly Complete or near complete destruction of cerebral hemispheres with extreme dilation of ventricles Catastrophic injury to brain < 28 weeks gestation Multiple possible causes: in utero carotid occlusion, CMV or toxoplasma infection Unlike anencephaly, cranium is intact

Mega Cisterna Magna aka Retrocerebellar Arachnoid Pouch, Blake’s Cyst Enlarged cisterna magna Communicates with subarachnoid spaces Posterior fossa = normal size Unlike arachnoid cysts: No mass effect on 4th ventricle

Mega Cisterna Magna ?Normal Variant Often an incidental finding ?Accuracy of diagnosis of MCM in this study?

Dandy Walker Malformation Core features: Absence (partial or complete) of the cerebellar vermis Cyst like dialation of the 4th ventricle Commonly present: Cerebellar hemispheres underdeveloped, displaced superiorly Hydrocephalus RITE 2008 question 317

Dandy Walker Malformation

Dandy-Walker Malformation

Dandy Walker Malformation Clinical Findings Usually evident in infancy Apnea, hypo/hypertonia, motor delays, nystagmus, titubation, hydrocephalus Sudden unexpected death, without herniation (vascular compromise from local ICP increases?) Treatment Cysto-/Ventriculo- peritoneal shunt Many associated syndromes

Walker-Warburg Syndrome Dandy-Walker plus ocular Abnormalities On 9q31, likely AR Other features: Hydrocephalus Lissencephaly

Craniorachischisis

Neural tube closure defects Neural plate is converted into a closed neural tube during 3-4th weeks of development

Neural tube closure defect Craniorachischisis: Most severe type of NTD in which brain and spinal cord are exposed to amniotic fluid and undergo degeneration May have well developed forebrain and optic nerves

Myelomeningocele

Neural Tube Closure Defects Myelomeningocele: 95% associated with Chiari II malformations, hydrocephalus may occur Malformations in spinal cord above the defect are common

Anencephaly Absence of both cerebral hemispheres Failure of neural tube to close anteriorly Infants are stillborn or die shortly after birth RITE 2010 question 319

Neural Tube Closure Defects Anencephaly: Absent or hypoplastic calvarium, “bat wing” deformity of sphenoid bone, only minimal cranial nerves II-V are present, pons/cerebellum/midbrain are grossly absent, aplasia of descending tracts May be associated with visceral anomalies including a large thymus and hypoplastic lungs

Anencephaly

Encephaloceles Herniation of intracranial contents through a skull defect Fluctuant balloony mass covered by a membrane or normal skin, may pulsate Occipital 75%, Frontal 25% Seen with other malformations and in syndromes

Encephalocele

Neural tube closure defects Encephalocele: In anterior version, herniation occurs through fronto-ethmoidal junction and appears as hypertelorism or bulging tissue May expand into nasal cavity (30%), pharynx, or orbit Seen in 90% of patients with Meckel-Gruber syndrome MG Syndrome –AR, lethal renal dysplasia, CNS malformations, polydactyly, pulmonary hypoplasia, hepatic developmental problems

Defective prosencephalization Forebrain develops between 25-30 days gestation from a midline vesicle that is generated from the closed anterior neuropore.

Holoprosencephaly

Holoprosencephalic children Hypoteloric Proboscis RITE 2010: question 310

Holoprosencephalic cat

Holoprosencephaly Defective clevage No division of prosencephalon (forebrain) No interhemispheric fissure Telencephalon = single lobe No olfactory bulbs or tracts Absence of midline structures

Holoprosencephaly Craniofacial dysplasia Cyclopia (single median eye) Ethmocephaly: nose replaced by a proboscis located above hypoteloric eyes Cebocephaly: hypotelorism and a nose with a single nostril Premaxillary agenesis: hypotelorism, flat nose, midline cleft lip

Holoprosencephaly Failure of prosencephalon to cleave into symmetric cerebral hemispheres Variable severity Alobar Semilobar Lobar

Semilobar Holoprosencephaly Some differentiation of hemispheres, posteriorly Diencephalon/Forebrain still fused in midline

Semilobar Holoprosencephaly

Lobar Holoprosencephaly Hemispheres separated (interhemispheric fissure present) Absent septum pellucidum Fused thalami Diffuse pachygyria Interdigitation of frontal gyri

Lobar Holoprosencephaly

Agenesis of the Corpus Callosum

Agenesis of the Corpus Callosum Corpus Callosum forms front to back; myelinates back to front If CC is partially absent, most likely posterior portion Anterior part alone can be absent in holoprosencephaly, frontal schizencephaly, frontal porencephalic cysts Thin CC: insult after completely formed (like PVL)

Agenesis of the Corpus Callosum

Agenesis of the Corpus Callosum

RITE 2008: question 254; RITE 2009 question 269

Schizencephaly Clefts in the cerebral hemispheres Flawed development of cortical mantle during cell migration in first trimester Genetic vs. acquired

Schizencephaly Most clefts near sylvian fissures Clefts extend from surface of cortex into a ventricle Neighboring gyral pattern abnormal Lips are formed by dysplastic gray matter (Porencephalic cyst lined by white matter)

Schizencephaly Open Lip: Lips of cleft are separated by CSF Closed Lip: Lips of cleft are in contact

Closed Lip Schizencephaly

Closed Lip Schizencephaly

Open Lip Schizencephaly

Schizencephaly Clinical Findings Often presents with seizures Can be focal or generalized; infantile spasms Hemiplegia

Hemimegalencephaly Brain volume increased from errors in neuroepithelial proliferation Histology: increase in number of cells (neurons and glia) and cell size Association of hemimegalencephaly with neuro-cutaneous disorders Linear sebaceous nevus syndrome and hypomelanosis of Ito

Hemimegalencephaly Macrocephaly at birth May have accelerated head growth in first few months of life Present with seizures, developmental delay, hemiparesis, hemihypertrophy Seizures sometimes require hemispherectomy or callosotomy

Hemimegalencephaly

Joubert Syndrome Molar Tooth Sign Complete agenesis of cerebellar vermis 4th ventricle enlarged (batwing shape) Other cerebral malformations, especially occipital encephaloceles

Joubert Syndrome

Chiari Malformation

Chiari Malformations Chiari I Extension of cerebellar tonsils (sometimes posterior vermis) into upper cervical canal Associated with syrinx Chiari II Displacement of cerebellar vermis (? medulla) in upper cervical canal Associated with lumbar myelomeningocele Chiari III Occipital encephalocele Chiari IV Absence of cerebellum

Chiari I with Syrinx

Chiari III

Lissencephaly Disorder of neuronal migration Abnormal migration of post-mitotic neurons from the ventricular zone to form the cortical plate Smooth cerebral surface: absence of gyri, abnormally thick cortex, abnormal lamination

Lissencephaly

Defects of cellular migration Miller-Dieker syndrome Lissencephaly Microcephaly Characteristic facies Upturned nares, micrognathia, high forehead, thin upper lip, low set ears Deletion on chromosome 17

X-linked defects of cellular migration (DCX mutation) Boys Lissencephaly Girls Subcortical band heterotopia Gray matter in the wrong places

RITE 2009: question 257

Polymicrogyria Too many small abnormal gyri Convolutions may not have sulci, or sulci might be bridged by fusion of overlying molecular layer which may give smooth appearance on surface Gray-white interface not distinct

Polymicrogyria Clinical findings depend on extent of abnormality Diffuse: severe developmental delay and hypertonia Focal deficits if focal Seizures common

Heterotopias Collections of normal-appearing neurons in an abnormal location Proposed mechanisms Damage to radial glial fibers Premature transformation of radial glia into astrocytes Radial glial surface molecule deficiency Isolated/multiple/diffuse Usually no cause apparent

Heterotopias Periventricular Nodular Heterotopias X-linked dominant (females only, lethal in males) Filamin A, aka Filamin 1 Failure of neuronal migration at an early stage from ventricular zone Filamin A anchors membrane proteins to actin cytoskeleton

Mobius syndrome Facial diplegia, bilateral abducens palsy, often involvement of other lower cranial nerves Pathogenesis: selective ischemia of midline and paramedian zones of developing brainstem