CNS Malformations SCOTT KULICH, M.D., Ph.D. RAFAEL MEDINA-FLORES, M.D. RONALD L. HAMILTON, M.D. Division of Neuropathology

Neural tube defects

Anencephaly Failure of closure of the anterior neuropore Common malformation Frog-like facies Area cerebrovasculosa Underdeveloped hypothalamus Adrenal cortical hyperplasia Multifactorial-Folic acid supplementation

Anencephaly

Anencephaly

SPINA BIFIDA myelomenigocele occultameningocele

SPINA BIFIDA Sacral dimple: dermal sinus track with spina bifida

MYELOMENINGOCELE Herniation of malformed cord + meninges through vertebral defect Usually associated with Arnold-Chiari and hydrocephalus Lumbosacral level most common

Myelomeningocele

Chiari II (Arnold Chiari) Cerebellar tonsillar herniation Small posterior fossa Extension of medulla below foramen magnum Kinking of medulla (Z- formation) Beaking of the quadrigeminal plate Hydrocephalus Myelomeningocele

Chiari II (Arnold-Chiari) Cerebellar tonsillar herniation Small posterior fossa Extension of medulla below foramen magnum Kinking of medulla (Z- formation) Beaking of the quadrigeminal plate Hydrocephalus Myelomeningocele

Arnold-Chiari (Chiari II)

Chiari I Malformation Sagittal MRI (T1) shows cerebellar tonsils 2-3 cm below foramen magnum, where the CSF space is narrow. There is no syrinx in the cervical cord & the 4 th ventricle is normal size & configuration.

Chiari I Malformation Chronic protrusion of the cerebellar tonsils less than 1.5 cm below the foramen magnum Most patients asymptomatic Some develop hydrocephalus

Dandy-Walker Malformation Dandy-Walker syndrome –Agenesis of cerebellar vermis –cystic dilatation of 4th venticle –enlargement of posterior fossa –Variable clinical manifestations –Hypothesized to result from arrest of cerebellar development prior to the 3rd month

DANDY-WALKER SYNDROME

CEREBELLAR MALFORMATIONS: VERMIAN (PALEOCEREBELLUM) Joubert syndrome –Clinical manifestations include episodic hyperpnea, ataxia, eye movement abnormalities, and MR –Familial –Agenesis of vermis, cystic dilatation of 4th venticle (but less than DWS) –Microscopically normal cerebellar cortex with numerous subcortical heterotopias

Holoprosencephaly Common associations: TORCH infections, fetal alcohol syndrome, trisomy 13 Classification: –Alobar –Semilobar –Lobar –Arrinencephaly

Holoprosencephaly Failure of the cerebral hemispheres to separate “face predicts brain”: cyclopia, proboscis, agnathia, cleft lip/ palate, etc. Most cases sporadic Common associations: maternal diabetes

Holoprosencephaly Cyclopia and cebocephaly

Holoprosencephaly Failure of the cerebral hemispheres to separate “face predicts brain”: cyclopia, proboscis, agnathia, cleft lip/ palate, etc. Most cases sporadic Common associations: maternal diabetes

Holoprosencephaly

Holoprosencephaly

Holoprosencephaly

Encephalocele -Herniation of brain through skull defect -Usually occipital, occasionally anterior (frontal) at bridge of nose (“nasal glioma”). -Asymmetric with overlying ulceration

AGENESIS OF CORPUS CALLOSUM May be total or partial –Partial usually affects posterior (splenium) May be sporadic or syndromic –Acardi (infantile spasms, MR, polymicrogyria) –Andermann (sensorimotor neuropathy, dysmorphic features) –Meckel-Gruber (occipital encephalocele, liver/kidney abnl) May be clinically silent

AGENESIS OF CORPUS CALLOSUM Abnormal cingulate gyrus with radiating gyral pattern

AGENESIS OF CORPUS CALLOSUM Bat wing shaped lateral ventricles Bundle of Probst

MICROENCEPHALY

MICROENCEPHALY “Small brain” Primary –with micro-cephaly (small head) Secondary –may have normocephaly –Neurodegenerative diseases »Ceroid lipofuscinosis (Batten’s disease)

MEGALENCEPHALY Brain weight > 2.5 standard deviation than mean Classification –Primary: familial, achondroplasia, isolated –Secondary: leukodystrophies (Alexander’s), neurocutaneous syndromes, errors of metabolism May be associated with olivary heterotopia in autistic patients 1/3 with macroscopic and 1/3 with microscopic abnormalities

CORTICAL DYSPLASIA Polymicrogyria

CORTICAL DYSPLASIA POLYMICROGYRIA

TUBEROUS SCLEROSIS

Wide, flat, firm gyri

TUBEROUS SCLEROSIS Candle gutterings

TUBEROUS SCLEROSIS SEGA

Sturge-Weber Disease Port-wine stain or nevus Flammeus tuypical of Sturge-Weber, occurring in V1 distribution.

Sturge Weber Disease CT: Calcification of gyrus in the parietooccipital region with focal cortical atrophy & ipsilateral enlargement of the choroid plexus.

Sturge-Weber Disease