CNS Pathology
Introduction
&
Congenital Abnormalities
• 2% body Wt but 20% Oxygen.
• Hypoxia First to get affected.
• No regeneration – Permanent
cells.
• Fluid tissue… Floats in CSF.
• Very delicate, less support.
• Limited space - Hard bony shell.
Congenital Abnormalities
Immature Brain
• Premature and very young fetuses have few
convolutions. The primary sulci are the calcarine,
parietal-occipital, and central sulci. They appear by
about gestational age 20 weeks.
• After that particularly after 25 weeks gestation
secondary convolutions are formed: The pre and
post central, superior temporal, and frontal gyri
• After 28 weeks there is a more brain specific
formation of the secondary and tertiary
convolutions. The premature brain does not have
any myelin except in the tegmentum of the
brainstem.
• Myelination of the corticospinal tracts is seen at
about 39 weeks gestation. The entire premature
and term infant brain appears white.
I. GENERAL POINTS
• The incidence of malformations is higher
in children with intrauterine growth
retardation and in multiple pregnancies.
• Race and geographic factors may be of
importance.
• The development of the brain continues
for years after birth and thus the term
congenital anomaly applies to some brain
conditions that develop postnatally.
• Inflammatory responses do not occur
before the sixth fetal month and parts
may be absorbed without trace of
neuroglial or connective tissue repair.
• The same anomaly may occur as a result
of genetic or environmental causes.
• Probably the most important factor in
teratogenesis is the timing of the insult,
followed by the specific nature of the
agent and genetic factors.
• The incidence of CNS malformations, giving rise to
mental retardation, cerebral palsy, or neural tube
defects, is estimated at 1% to 2%.
• Malformations of the brain are more common in the
setting of multiple birth defects.
• Prenatal or perinatal insults may either cause failure
of normal CNS development or result in tissue
destruction.
• Because different parts of the brain develop at
different times during gestation (and afterwards), the
timing of an injury will be reflected in the pattern of
malformation.
II. ETIOLOGY
• Genetic Factors: very few cerebral
anomalies are caused by simple Mendelian
inheritance, but some examples include:
– Forms of microcephaly inherited as autosomal
recessive
– Sex-linked variety of hydrocephalus
– Hereditary congenital facial paralysis- autosomal
dominant
– Some anomalies have a high risk of recurrence
within families
– Some anomalies are associated with inborn errors
of metabolism
• Cytogenetic Abnormalities
– Most important group are the trisomies,
e.g., Down's
– Others include translocations,
deletions (e.g., cri du chat), and sex
chromosomes (e.g., Turner's,
Klinefelter's)
• Maternal Age
• Maternal Infections (rubella, CMV).
Different patterns of malformation
correlate with mishaps (known or
unknown) at different time:
• Idiopathic (most of cases)
• Known causes include
– maternal alcoholism,
– mercury poisoning,
– lead poisoning,
– radiation,
– exposure to vincristine
– folic acid deficiency
– hypervitaminosis.
III. Neural tube defects
• Among the earliest stages in brain development is
the formation of the neural tube, the inside of which
will become the ventricular system and the wall of
which will become the brain and spinal cord.
• Failure of a portion of the neural tube to close, or
reopening after successful closure, may lead to one
of several malformations.
• All are characterized by abnormalities involving some
combination of neural tissue, menginges, and
overlying bone or soft tissues.
• Collectively, neural tube defects are the most
frequent CNS malformations
III. NEURAL TUBE DEFECTS
(DYSRAPHIC DISORDERS)
• Anencephaly
– Basically a complete absence of the
cerebral hemispheres.
– The calvarium is hypoplastic or absent.
– If the occipital bones are formed,
rudimentary brain stem and cerebellum
may be found.
– Most common anomaly in humans.
Anencephaly
• Encephalocele and Cranial
Meningocele
– Consists of a protrusion of brain or
meninges through a cranial defect.
– Most frequent in the occipital region,
i.e., 75-80% of cases.
– The mass of tissue is often
voluminous and is usually attached to
one of the cerebral hemispheres by a
narrow pedicle.
– Genetic and environmental factors
may be of etiologic importance.
• Spinal Meningocele, Myelomeningocele,
and Myelocele
– All are usually associated with spina bifida.
Meningocele consists of herniation of both dura
and arachnoid through a vertebral defect, the
spinal cord remaining in its normal position.
– Meningomyelocele consists of the above in
addition to the spinal cord (closed) being herniated
as well.
– Myelocele consists of all the above, but the spinal
cord is open and flat with CSF leaking onto the
exposed surface.
– Hydrocephalus commonly occurs in association
with all of the above.
IV. ARNOLD CHIARI MALFORMATION
• Complex Deformity of the Brain and
Cerebellum (Four types):
– Type I: LESS SEVERE FORM
• Ectopia of the cerebellar tonsils.
• May be a cause of late onset
hydrocephalus,
• May be associated with a minor deformity
of the medulla.
– Type II: MOST COMMON TYPE
• By far the most common type seen in neonates
• Usually associated with a lumbar myelomeningocele
• Consists of lengthening of the vermis and tonsils of the
cerebellum and their downward displacement through the
foramen magnum into the spinal canal.
• Characteristic Z shaped kink at the junction of the
medulla and cord.
• Cranial vault anomalies.
– Type III: VERY RARE TYPE
• Cervical spinal bifida,
• the entire cerebellum being herniated through the
foramen magnum.
– Type IV:
• Cerebellar hypoplasia.
• cerebellar
tonsils
herniating
through the
foramen
magnum• a characteristic
of ArnoldChiari
malformation
• ACM (in practice this refers to
type II) usually associated with
communicating hydrocephalus.
• The malformation develops early
in gestation at the age of 10
weeks.
Clinical Correlation
The Arnold Chiari malformation may be
associated with normal intellagence (if the
hydrocephalus is shunted) or mental
retardation.
It is also associated with lower limb
paralysis and urinary and fecal
incontinence due to the
meningomyelocoele.
Type I can cause neck pain and cranial
nerve signs and may sometimes have to
be treated with surgical decompression.
V. ANOMALIES OF THE SPINAL
CORD
Usually these are described in the adult,
so they could represent acquired lesions.
• Hydromyelia: is an over distension of the
central canal. (Local dilatation of the
central canal of the spinal cord.)
– in the lumbar region
– may be asymptomatic and only an incidental
finding at autopsy
– may be associated with ACM in 40% of cases
of the latter.
• Spina bifida (congenital anomaly)
– Defective closure of the vertebral
column.
– Spina bifida is one of the most
serious neural tube defects
compatible with prolonged life.
– Its severity varies from the occult
type with no findings to a
completely open spine
(rachischisis) with severe
neurologic disability and death.
– In spina bifida cystica, the protruding sac can
contain meninges (meningocele), spinal cord
(myelocele), or both (myelomeningocele).
– Spina bifida is most common in the lower
thoracic, lumbar, or sacral region and usually
extends for 3 to 6 vertebral segments.
– The sac in a myelomeningocele usually
consists of meninges with a central neural
plaque. If not well covered with skin, the sac
can easily rupture, increasing the risk of
meningitis.
VI. MALFORMATIONS OF THE
CEREBELLUM
• Agenesis of the Cerebellum: uncommon
• Hypoplasia
• Dandy Walker Malformation (absence of
cerebellar vermis and dilatation of 4th ventricle)
• L'hermitte Duclos Disease (Dysplastic granulomolecular hypertrophy of the cerebellar cortex)
VII. HOLOPROSENCEPHALY
(ARHINENCEPHALY)
• Covers a large spectrum of anomalies from
cyclopia to agenesis of one olfactory bulb.
• In the most severe form, there is an anterior
holosphere with no interhemispheric fissure and
a single ventricle.
• The brain is often smaller than normal and the
olfactory bulbs and tracts are absent.
• Optic nerves are absent and gyri are broad and
have an abnormal pattern.
• Brain stem and cranial nerve structures may be
normal.
Semilobar holoprosencephaly
Face of an infant with semilobar
holoprosencephaly •Shows
closeset eyes, absent nose
and abnormal mouth often
seen in this form of
holoprosencephaly
A single large ventricle with
fusion of midline structures,
including thalami. The
affected fetuses and
neonates typically have
severe facial defects, such
as cyclopia, as well.
Underlying chromosomal
abnormalities, such as
trisomy 13, or maternal
diabetes mellitus are
possible causes, but some
cases are sporadic.
• The large single ventricle seen here
inside a single hemisphere
represents the "alobar" form of
holoprosencephaly in which there
was no division of hemispheres.
• Cyclopia and agnathia are the
major facial associations.
• Rhinencephaly is
characterized by a
proboscis-like nose above a
single median eye. Cyclopia
is also known as
synophthalmia, which is the
fusion of the eyes
THE PROBOSCIS MONKEY
VIII. ANOMALIES OF CELL
MIGRATION
• Ectopias and Heterotopias: These terms
refer to misplaced groups of neurons,
such as an island of gray matter in the
subcortex.
– More common in the cerebellum than the
cerebrum.
• Cerebellar Cortical Dysplasia.
IX. ABNORMAL SURFACE
CONFIGURATIONS OF THE BRAIN
• Agyria (lissencephaly): Total absence of
gyri
• Pachygyria: A few broad malformed gyri
varying in size and number
• Polymicrogyria: An increased number of
gyri some of which may be abnormally
small.
• This is a horizontal section of a microcephalic brain which
shows areas of no convolutions lissencephaly or smooth
brain and areas of large gyri -pachygyria.
• Note how thick the cortex is and how thin the white matter
characteristic of lissencephaly and pachygria
• Coronal section through this brain shows the cortex to be thrown
into numerous small gyri characteristic of polymicrogyria.
• Note the enlarged ventricles and small size of the white matter.
• These patients are usually retarted and may have seizures or other
neurologic findings
X. MICROCEPHALY
• Small brain usually associated with a small
head. Brain Weight < 900 g.
• Congenital microcephaly may follow
intrauterine infections with rubella, CMV,
Toxoplamosis.
• Congenital microcephaly is also a part of
many chromosomal abnormalities and other
syndromes:
Gross chromosomal
abnormalities
• Trisomy 18
• Trisomy 13
• Wolf-Hirschhorn
syndrome
• Cri du Chat syndrome
• Partial deletion of long
arm of 13
Contigous gene syndromes
• Miller-Dieker syndrome
• Langer-Giedion
syndrome
• Prader-Willi syndrome
• Aniridia-Wilms tumour
syndrome
Autosomal
recessive
disorder
• JohansonBlizzard
syndrome
• Seckel
syndrome
• Smith-LemliOPitz
syndrome
• Coffin-Siris
syndrome
Rubinstein-Taybi
syndrome
Maternal PKU
Coronal sections through to half brains at the
level of the thalamus showing a normal adult
brain on right and a smaller, microcephalic
brain on left.
XI. MEGALENCEPHALY
Macrencephaly
• Proportionate enlargement of the whole brain, usually
associated with the presence of a variable mental
aberration.
• Well-formed, but too big (>1800 gm). Causes:
– tuberous sclerosis,
– cerebral lipidoses,
• Alexander's leukodystrophy.
• Unilateral megalencephaly or hemimegalencephaly is
a rare condition and is characterized by the
enlargement of one-half of the brain.
– Children with this disorder may have a large, sometimes
asymmetrical head.
– Often they suffer from seizures and mental retardation.
XII. AGENESIS OF THE
CORPUS CALLOSUM
• May be part of a complex malformation
or be totally or partially absent in an
otherwise normal brain.
• Patients can be of normal intelligence
but lack ability to transfer information
from one hemisphere to the other
XIII. NEUROCUTANEOUS
SYNDROMES
•
•
•
•
Tuberous Sclerosis
von Hippel Lindau's Angiomatosis
Sturge Weber Syndrome
von Recklinghausen's Disease
• This is tuberous sclerosis, an autosomal
dominant condition characterized by mental
retardation and seizures beginning early in life.
The characteristic feature is the presence of
"tubers" which are enlarged and firm, whitened
gyri. A "tuber" is seen at the arrow.
• Syringomyelia / syringobulbia:
– Probably acquired later in life, but discussed
here.
– There is a tubular cavity in the center of the
cord (generally cervical) and/or brainstem
(bad), with surrounding gliosis.
– There is loss of pain and temperature (since
the crossing spinothalamic tract is
damaged) over the corresponding levels.
– Eventually, other sensory and motor
pathways may be damaged.
– Most often these conditions are idiopathic;
known causes include cord tumors and
Arnold-Chiari.
• Neuroepithelial cysts probably arise from
faulty migration during embryogenesis.
They gradually grow, and become
symptomatic in adult life.
– The best-known are the "colloid cysts" that
occlude the foramen of Munro, often causing
headache only when the head remains in a
particular position.
• Arachnoid cysts may be large and require
surgical removal.
• Cerebral palsy: a brain defect present at (or
presenting shortly after) birth, typically with
motor and often cognitive problems.
Thank you!