NeuroPathology:

Congenital Abnormalities
Malformations
Agenesis of the Corpus Callosum
Arnold-Chiari Malformation
Arrhinencephaly
Cyclopia
Dandy-Walker
Lissencephaly
Polymycrogyria

Migration Defects:
Agyria-Pachygyria

Neural Tube Defects

-Anencephaly
-Spina Bifida/Meningomyelocele

Toxins/Metabolic
Erythroblastosis Fetalis/Kernicterus
Neuronal Storage Diseases

Miscellaneous
Germinal Matrix Zone Hemorrhage
Hydrocephalus
Holoprosencephaly
Sturge-Weber Disease
White Matter Lesions
Leukodystrophy
Periventricular leukomalacia

Described elsewhere:
Arteriovenous Malformations (see BENIGN doc)
CADASIL- Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (see BENIGN doc)
 Arnold-Chiari Malformation
*Second most common malformation (after Neural tube defects)
*Most common cause of congenital hydrocephalus

A Chiari malformation (sometimes called an Arnold Chiari) is a

malformation of the brain. It consists of a downward displacement
of the cerebellar tonsils through the foramen magnum, sometimes
causing non-communicating hydrocephalus as a result of
obstruction of cerebrospinal fluid (CSF) outflow. The cerebrospinal
fluid outflow is caused by phase difference in outflow and influx of
blood in the vasculature of the brain. It can cause headaches,
fatigue, muscle weakness in the head and face, difficulty
swallowing, dizziness, nausea, impaired coordination, and, in severe
cases, paralysis.

Courtesy of Nimmy Rosh http://radiology-files.blogspot.com/2013/05/chiari-malformation-arnold-chiari.html

High Yield
● Herniation of cerebellar tonsils and caudal medulla into upper cervical canal
● Midbrain/tectal “beaking” & dorsal “S” shaped medullary fold
● Aqueductal stenosis or IVth ventricul outlet obstruction → hydrocephalus
● Craniolacunia, patchy thinning of calvarium, 90%
● Associated with Myelocele/meningomyelocele in 100% of cases (see below)

The first image shows a view from behind of a hindbrain in Chiari’s type II malformation (most common type) . Cerebellar tonsils protrude through the foramen
magnum. ( PathologyOutlines) The other images show the differences in a normal spine and one with varying degrees of spina bifida. (from Elly Wombwell)

HIGH YIELD NEUROPATHOLOGY STUDY NOTES: Congenital Anomalies Tiffany M. Graham, M.D.
Last Updated: 3/4/19 1 www.IHeartPathology.net
 Dandy-Walker Malformation
The Dandy-Walker syndrome is hydrocephalus associated with a posterior fossa cyst and
abnormal development of the cerebellum, a portion of the brain located near the base of the
skull and important to voluntary muscle movement, balance and posture. This malformation
occurs when openings that allow cerebrospinal fluid to move into the space surrounding the
surface of the brain fail to open. The condition may prompt any of a number of brain and
central nervous system abnormalities. When treatment is necessary, the posterior fossa
cyst needs to be shunted to allow proper flow of cerebrospinal fluid. If there is no
communication between the posterior fossa cyst and the lateral ventricles, then the lateral
ventricles need to be shunted also.

High Yield:
● Midline cerebellar malformation
○ Agenesis/hypoplasia of cerebellar vermis
○ “Posterior Fossa Cyst”
● IVth ventricular outflow obstruction → Hydrocephalus, large posterior fossa,
with markedly dilated IVth ventricle

HIGH YIELD NEUROPATHOLOGY STUDY NOTES: Congenital Anomalies Tiffany M. Graham, M.D.
Last Updated: 3/4/19 2 www.IHeartPathology.net
 Diagnosis by Photo
Agenesis of the Corpus Callosum

● Absence of both corpus callosum AND cingulate gyrus

● “Bat-wing” appearance of lateral ventricles on coronal view
● May be asymptomatic or associated with other CNS/systemic abnormalities

Arrhinencephaly Cyclopia

Germinal Matrix Zone Hemorrhage

HIGH YIELD NEUROPATHOLOGY STUDY NOTES: Congenital Anomalies Tiffany M. Graham, M.D.
Last Updated: 3/4/19 3 www.IHeartPathology.net
 Holoprosencephaly
Due to defective prosencephalic diverticulation
Molecular
○ Trisomy 13 or Trisomy 18
○ Sonic hedgehog (SHH) gene mutation
■ SHH is a secreted protein that
regulates neurulation.
Risk factors
○ Maternal diabetes
○ Infection (Toxoplasmosis, Syphilis, Rubella)

Hydrocephalus
Most common cause is obstruction of CSF flow.

Can be due to increased CSF production (such as choroid plexus papilloma)

Congenital hydrocephalus due to:

- Malformation or disruption in development of aqueduct of Sylvius or hindbrain

Cranial sutures are open → head enlargement

Migration Defects
Agyria-Pachygyria Lissencephaly (“Smooth brain”)
Miller-Dieker Syndrome- Seizures, mental retardation,
lissencephaly. Due to deletion of Chr 17p13.3 (90%)
LIS1 gene.

Polymicrogyria
“Many small gyri” with abnormal cortical lamination

Heterogenous etiology:
Intrauterine ischemia
Infection
Multiple genetic associations

HIGH YIELD NEUROPATHOLOGY STUDY NOTES: Congenital Anomalies Tiffany M. Graham, M.D.
Last Updated: 3/4/19 4 www.IHeartPathology.net
 Neural Tube Defects
NTDs are the most common form of CNS malformation; result from defective neurulation
Occurs during in the first 3-4 weeks of gestation; Risk is reduced by taking folic acid during gestation.
NTDs be detected by measuring maternal serum AFP (alpha fetoprotein); confirmed with ultrasound

HIGH YIELD NEUROPATHOLOGY STUDY NOTES: Congenital Anomalies Tiffany M. Graham, M.D.
Last Updated: 3/4/19 5 www.IHeartPathology.net
Anencephaly
● Absence of all or part of cerebrum; rudimentary brain tissue “area cerebrovasculosa”, and without skull.
● Incompatible with life

Meningomyelocele
● Midline lumbosacral defect associated with protrusion of portions of spinal cord and/or meninges

HIGH YIELD NEUROPATHOLOGY STUDY NOTES: Congenital Anomalies Tiffany M. Graham, M.D.
Last Updated: 3/4/19 6 www.IHeartPathology.net
 Sturge-Weber Disease
General
● Rare congenital vascular disorder
○ Facial lesion (distribution of trigeminal nerve)
○ + Similar vascular lesion intracranially
● Unilateral

Clinical Correlation
● Hemangiomatous facial lesion = Port wine stain (nevus flammeus) (Cutaneous
capillary malformation)
● Abnormal capillary venous vessels in the brain and eye → glaucoma, seizures,
stroke, and intellectual disability/ retardation
● Hemiatrophy of body

Imaging
● Leptomeningeal venous angioma, calcification

Susceptibility-weighted MRI (Panel A) revealed abnormal leptomeningeal capillary vessels along the right cerebral
convexity. Sturge–Weber syndrome, a rare congenital vascular disorder characterized by a cutaneous capillary
malformation, also called port-wine birthmark (Panel B shows the patient’s face 2 years after the initial presentation),
From Dr. Shivang Desai & Dr. Charles Glasier; NEJM; 2017; 377:e11; DOI: NEJMicm1700538

HIGH YIELD NEUROPATHOLOGY STUDY NOTES: Congenital Anomalies Tiffany M. Graham, M.D.
Last Updated: 3/4/19 7 www.IHeartPathology.net
 White Matter Lesions
Adrenoleukodystrophy
● Peroxisomal disorder: Defect in peroxisomal membrane protein that imports acyl CoA synthetase into peroxisome.
● X-linked (different from other metabolic diseases)
● Parieto-occipital demyelination
● Adult form: spinal cord & peripheral nerves

Krabbe’s
Leukodystrophy
Accumulation of galactosyl sphingosine in enlarged macrophages within
perivascular spaces within the white matter produces so-called “globoid cells”

Metachromatic
Leukodystrophy
● Diffuse symmetrical dysmyelination
● Occipital to frontal progression
● Sparing of subcortical U-fibers

Periventricular Leukomalacia

HIGH YIELD NEUROPATHOLOGY STUDY NOTES: Congenital Anomalies Tiffany M. Graham, M.D.
Last Updated: 3/4/19 8 www.IHeartPathology.net
 Status Marmoratus
“Marbled State”

Normal Brain for Comparison

HIGH YIELD NEUROPATHOLOGY STUDY NOTES: Congenital Anomalies Tiffany M. Graham, M.D.
Last Updated: 3/4/19 9 www.IHeartPathology.net