Page 836 - Robbins Basic Pathology by Vinay Kumar, Abul K. Abbas, Jon C. Aster

822 C H A P T E R 22 Central Nervous System
subdural hematomas because their bridging veins are
thin-walled.
Subdural hematomas typically become manifest within
the first 48 hours after injury. They are most common over
the lateral aspects of the cerebral hemispheres and may be
bilateral. Neurologic signs are attributable to the pressure
exerted on the adjacent brain. Symptoms may be localizing
but more often are nonlocalizing, taking the form of
headache, confusion, and slowly progressive neurologic
deterioration.
MORPHOLOGY
An acute subdural hematoma appears as a collection of
freshly clotted blood apposed to the contour of the brain
surface, without extension into the depths of sulci (Fig. 22–
13, C ). The underlying brain is flattened, and the subarach-
noid space is often clear. Typically, venous bleeding is
self-limited; breakdown and organization of the hematoma
take place over time. Subdural hematomas organize by lysis
of the clot (about 1 week), growth of granulation tissue from
the dural surface into the hematoma (2 weeks), and fibrosis
(1 to 3 months). Organized hematomas are attached to the
dura, but not to the underlying arachnoid. Fibrosing lesions
may eventually retract, leaving only a thin layer of connective
tissue (“subdural membranes”). Subdural hematomas com-
monly rebleed (resulting in chronic subdural hemato-
mas), presumably from the thin-walled vessels of the
granulation tissue, leading to microscopic findings consistent
with hemorrhages of varying age. Symptomatic subdural
hematomas are treated by surgical removal of the blood and
associated reactive tissue.
S U M M A RY
Central Nervous System Trauma
• Physical injury to the brain can occur when the inside of
the skull comes into forceful contact with the brain.
• In blunt trauma, if the head is mobile there may be brain
injury both at the original point of contact (coup injury)
and on the opposite side of the brain (contrecoup injury)
owing to impacts with the skull.
• Rapid displacement of the head and brain can tear axons
(diffuse axonal injury), often causing immediate severe,
irreversible neurologic deficits.
• Traumatic tearing of blood vessels leads to epidural hema-
toma, subdural hematoma, or subarachnoid hemorrhage.
CONGENITAL MALFORMATIONS
AND PERINATAL BRAIN INJURY
The incidence of CNS malformations, giving rise to mental
retardation, cerebral palsy, or neural tube defects, is esti-
mated at 1% to 2%. Malformations of the brain are more
common in the setting of multiple birth defects. Prenatal
or perinatal insults may either interfere with normal
CNS development or cause tissue damage. Since different
parts of the brain develop at different times during gesta-
tion, the timing of an injury will be reflected in the pattern
of malformation; earlier events typically lead to more
severe phenotypes. Mutations affecting genes that regulate
the differentiation, maturation, or intercellular communi-
cation of neurons or glial cells can cause CNS malformation
or dysfunction. Additionally, various chemicals and infec-
tious agents have teratogenic effects.
Not all developmental disorders are characterized by
specific, recognizable gross or microscopic findings, yet
such disorders may nevertheless be associated with pro-
found neuronal dysfunction. Genetic underpinnings for
various forms of autism have emerged recently; many of
the implicated genes contribute to the development or
maintenance of synaptic connections. Similarly, Rett syn-
drome is an X-linked dominant disorder associated with
mutations in the gene encoding methyl-CpG–binding
protein-2 (MeCP2), a regulator of epigenetic modifications
of chromatin. Development in affected girls initially is
normal, but neurologic deficits affecting cognition and
movement appear by the age of 1 to 2 years, highlighting
the importance of epigenetic processes in neuronal devel-
opment and synaptic plasticity.
Malformations
Neural Tube Defects
On of the earliest steps in brain development is the forma-
tion of the neural tube, which gives rise to the ventricular
system, brain and spinal cord. Partial failure or reversal of
neural tube closure may lead to one of several malforma-
tions, each characterized by abnormalities involving some
combination of neural tissue, meninges, and overlying
bone or soft tissues. Collectively, neural tube defects consti-
tute the most frequent type of CNS malformation. The
overall recurrence risk in subsequent pregnancies is 4% to
5%, suggesting a genetic component. Folate deficiency
during the initial weeks of gestation also increases risk
through uncertain mechanisms; of clinical importance, pre-
natal vitamins containing folate can reduce the risk of
neural tube defects by up to 70%. The combination of
imaging studies and maternal screening for elevated
α-fetoprotein has increased the early detection of neural
tube defects.
The most common defects involve the posterior end
of the neural tube, from which the spinal cord forms.
These can range from asymptomatic bony defects (spina
bifida occulta) to severe malformation consisting of a flat,
disorganized segment of spinal cord associated with an
overlying meningeal outpouching. Myelomeningocele is an
extension of CNS tissue through a defect in the vertebral
column that occurs most commonly in the lumbosacral
region (Fig. 22–14). Patients have motor and sensory defi-
cits in the lower extremities and problems with bowel and
bladder control. The clinical problems derive from the
abnormal spinal cord segment and often are compounded
by infections extending from the thin or ulcerated overly-
ing skin.
At the other end of the developing CNS, anencephaly is
a malformation of the anterior end of the neural tube that
leads to the absence of the brain and the top of skull. An