CNS ANOMALIES

2. Fetal central nervous system anomalies
Alexandria university
Departement of obstetric and gynecology
Fetal medicine course
Prepared by Dr Onesphore NKUNZIMANA

3.  Central nervous system (CNS) malformations are some of the most common
congenital abnormalities encountered at birth.
 The true incidence of these anomalies is, however, probably underestimated
because many cerebral malformations will only be discovered later on in
life. the incidence may be as high as 1%.
 Detection of CNS anomalies is one of the most compelling motivations for
the routine use of sonography in pregnancy.
 Many subtle anomalies that are poorly understood are now detected
antenatally.
The consequences of these anomalies are difficult to predict.
This is a source of anxiety to the couples, requires difficult decisions and may
eventually lead to the loss of normal fetuses.

4. I. Ventriculomegaly
 Def: Enlargement of the lateral cerebral ventricles .
It represents a common endpoint of various pathological processes with
different
Prognoses.
 Incidence : 1% of fetuses..
0,1% at births. Frequent in males than females.
 Ultrasound diagnosis:
Bilateral or unilateral dilation of the lateral cerebral ventricles observed in
the standard transverse section of the brain.
The normal measurement is <10 mm between 15 and 40 weeks’ gestation.
Subdivided according to the diameter of the lateral ventricle into mild (10-12
mm), moderate (13-15 mm) and severe (>15 mm).

5.  Associated abnormalities:
•Chromosomal defects, mainly trisomies 21, 18 or 13, found in 10% of cases.
•Cerebral and non-cerebral defects and genetic syndromes are found in 50% of
cases.

6.  Investigations:
Detailed ultrasound examination, Invasive testing for karyotyping and array, TORCH test, Maternal blood testing
for antiplatelet antibodies.
Fetal brain MRI at ≥32 weeks for diagnosis of abnormalities of neuronal migration, such as lissencephaly.
 Follow up: Ultrasound scans every 4 weeks.
 Delivery: Standard obstetric care and delivery or CS if the fetal head HC >40 cm
 Prognosis:
Isolated mild / moderate: neurodevelopmental delay in 10% of cases.
Isolated severe: 10 year survival 60%, severe mental handicap 50%.
 Recurrence:
 Isolated <1%. Increases to 5% if there is a history of affected fetus or sibling.
 Part of infection: no increased risk.
 Part of trisomies: 1%.
 X-linked hydrocephaly: 50% of males.
 Associated with alloimmune thrombocytopenia and no treatment: 100%

7. II. Neural tube defects
1. Anencephaly is the absence of the cranial vault and telencephalon. The
diagnosis relies upon the demonstration of the absence of the cranial vault.
Most cases can be confidently identified at the 11–13 weeks’ scan by the lack of an
ossified calvarium.
At 12 weeks acrania is suspected by absence of the
ossified skull and distortion of the brain (exencephaly).
At >16 weeks the brain is destroyed (anencephaly).

8. o The terms acrania and excencephaly are also used and represents an early
stage in the development of anencephaly. .
o The sequence acrania–exencephaly–anencephaly is due to progressive
destruction of the exposed fetal brain by chemical and traumatic insults in
the amniotic fluid.
o The outcome is uniformly fatal.
 Supplementation of the maternal diet with folate (5 mg/day) for 3 months
before and 2 months after conception reduces the risk of recurrence by
about 75%.

9. 2. Spina bifida subdivided into open and closed forms.
 Open spina bifida: full-thickness defect of the skin, soft tissues and vertebral
arches exposing the neural canal.
 Site: lumbosacral (65%), sacral (24%), thoracolumbar (10%), cervical (1%).
 Diagnosis systematic examination from the cervical to the sacral region by both
transversal and longitudinals overview.
 By transverse scan,
the normal neural arch: closed circle with an intact skin;
in spina bifida:U’-shaped with bulging meningocele or
myelomeningocele.
 the sagittal scan is the best for assessment of
The extent of the defect and associated kyphoscoliosis.

10. It is associated with the Arnold-Chiari II malformation with caudal
displacement of the brain stem and obliteration of the cisterna magna.
 At 11-13 weeks’ gestation, In most cases of open spina bifida the diameter of
the brain stem is increased, the distance between the brain stem and the
occipital bone (BSOB) is decreased and the ratio of the brain stem to BSOB is
>1.0.
 In the second-trimester, more than 95% of fetuses have a lemon sign and a
banana sign.
 A variable degree of ventricular enlargement is present in virtually all cases
of open spina bifida at birth, but in only about 70% of cases in the mid-
trimester.

11.  Associated abnormalities: Chromosomal abnormalities (trisomy 18),
single mutant genes, diabetes mellitus and antiepileptic drugs are
found in 10% of the cases.
 Investigations:
Detailed ultrasound examination.
Fetal karyotyping in the presence of associated anomalies.
 Follow up:
 Follow-up scans every 4 weeks to monitor evolution of ventriculomegaly,
possible kyphoscoliosis and development of talipes.

12.  Fetal therapy:
In utero closure of spina bifida , reduces the need for postnatal shunt placement and may improve
motor and urologic function.
 Delivery:
Standard obsetric care and delivery.
 Prognosis:
 The 5-year mortality rate is about 35%, with 20% dying during the first 12 months of life. About
25% of fetuses with spina bifida are stillborn.
 The surviving infants usually have paralysis in the lower limbs and double incontinence; despite
the associated hydrocephalus requiring surgery, intelligence is often normal.
 Recurrence:
 Affected parent or one sibling: 5%.
 Two affected siblings: 10%.
 Supplementation of the maternal diet with folate (5 mg/day) for 3 months before and 2 months
after conception reduces the risk of recurrence by about 75%.

13.  Closed spina bifida is characterized by a vertebral schisis covered by skin. Most defects are
small, involving only few veretebral segments, and the classical intracranial signs are
always absent.
 diagnosis with sonography is difficult and is only possible in those cases associated with a
subcutaneous mass, a meningocele or lipoma, overlying the defect
 . The outcome of closed spina bifida
is difficult to predict.
 These infants do not develop
Arnold–Chiari malformation
and hydrocephalus, but they may
suffer from neurologic sequelae of
variable entity.

14. 3. cephalocele protrusion of intracranial contents through a bony defect of
the skull.
mostly midline, occipital (85%), but can be parietal (15%) and rarely frontal.
Encephaloceles meningocele are characterized respectively by the presence
of brain tissue or the meninges inside the lesion.
 Associated abnormalities:
 Chromosomal defects, mainly trisomies 13 or 18, are found in about 10% of
cases.
 Cerebral and non-cerebral defects and genetic syndromes are found in
>60% of cases.
 The most common genetic syndromes are: Meckel-Gruber
syndrome , Walker-Warburg syndrome and amniotic band syndrome.

15.  Delivery: hospital with neonatal intensive care and pediatric
neurosurgery at 38 weeks by CS at 38 weeks to avoid trauma to the
exposed brain tissue.
 Prognosis: Depends on the size, content and location of the
encephalocele.
There is Neurological handicap in >50% of survivors.

16. III. Midline anomalies
1. holoprosencephalies are complex abnormalities of the forebrain that share
in common an incomplete separation of the cerebral hemispheres and
formation of diencephalic structures.
 Ultrasound diagnosis:
Abnormalities from incomplete cleavage of the forebrain observed in the
standard transverse sections of the brain.
There are 4 types:
Alobar: fusion of the cerebral hemispheres
with a single ventricle.
Semilobar: cerebral hemispheres and lateral
ventricles are fused anteriorly but separated posteriorly.

17. Lobar: cerebral hemispheres are separated both anteriorly and
posteriorly, but there is partial fusion of the frontal horns
of the lateral ventricles, absence of septum pellucidum and
abnormalities of the corpus callosum, cavum septum pellucidum
and olfactory tract.
 Syntelencephaly, the anterior and occipital areas of the brain are fully
cleaved as in the lobar type, but unlike this, there is no parietal cleavage and
therefore the Silvian fissures are vertically oriented and abnormally
connected across the midline over the vertex of the brain.
 Lobar holoprosencephaly is detectable at >18 weeks’ gestation, but the other
three types can be detected at the 11-13 weeks scan.

18.  Associated abnormalities:
Chromosomal defects, mainly trisomies 13 or 18, are found in >50% of cases at 12
weeks’ gestation.
Genetic syndromes are found in 20% of cases.
 Alobar and lobar holoprosencephaly are associated with microcephaly and
midfacial defects in 80% of cases.
 Investigations:
 Detailed ultrasound examination, karyotyping and array and Fetal MRI(for
confirmation of diagnosis in cases of suspected lobar holoprosencephaly).
 Prognosis:
Alobar and semilobar: usually lethal within the first year of life.
Lobar: life expectancy may be normal but usually with severe developmental
delay and visual impairment.

19. 2. Corpus callosum agenesis
 Prevalence: 1 in 300 births.
 Ultrasound diagnosis:
 Absence of the septum cavum pellucidum
and tear-drop appearance of dilated posterior
part of the lateral ventricles (‘tear drop’) in the standard transverse view
of the brain at >18 weeks’ gestation.
 Complete or partial absence of the corpus
callosum in a mid-sagittal view of the brain.
 Abnormal course of the pericallosal artery.
 The normal length of the corpus callosum at
20 weeks’ gestation is 18-20 mm.

20.  Associated abnormalities:
 Chromosomal abnormalities (trisomies 8, 13 or 18, deletions and duplications)
are found in 20% of cases.
 In about 50% of cases there is an association with any one of 200 genetic
syndromes, defects in the central nervous system or defects in other systems.
 Investigations:
Detailed ultrasound examination, karyotyping and array, TORCH test.
 Fetal brain MRI at ≥32 weeks for diagnosis of abnormalities that are not
detectable by ultrasound, such as grey matter heterotopias, late sulcation and
migration anomalies.
 Prognosis:
Isolated: neurodevelopmental delay in 30% of cases.
Other defects: prognosis could be poor depending on the type of defect.

21. IV. Cystic and cyst-like abnormalities of the
posterior fossa
 Abnormal fluid collections in the fetal posterior fossa
encompass a wide spectrum of different entities, ranging
from normal variants to severe anomalies.

22. V. Destructive cerebral lesions
 Many congenital anomalies of the brain are not the consequence of an
embryogenetic malformative process but are due to a destructive process.
The pathophysiology is frequently unclear and the conditions remain
idiopathic.
A link with obstetric complications of a different nature is frequently found.

23. 1. Intracranial hemorrhage (ICH) frequent complication of prematurity. Rarely,
it may occur antenatally, as a consequence of fetal thromobocy-topenia and
other coagulopathies, trauma, or other yet unexplained factors.
 The sonographic appearance is variable depending upon the type, the
severity and the time since it occurred.

24.  complications infarct and destruction of the surrounding white matter
with related concequencies.
 The prognosis is favorable with grade 1 and 2 hemorrhages and is
severe with grade 3 and 4 lesions.
 Most cases identified prenatally belong to grade 3 and 4, and in a
review of the literature, 50% died perinatally and 50% of survivors were
neurologically compromised.
 Fetal alloimmune thrombocytopenia must be excluded and Fetal MRI is
helpful in distinguishing hemorrhage from other intracranial
pathologies.

25. 2. Fetal stroke: antenatally, the etiology is heterogeneous, but thus far
most cases have been identified in monochorionic twin gestation following
twin-to-twin transfusion.
 The appearance is variable.
 In the following stages, microencephaly, cystic intra-parenchymal
cavities and cortical malformations will develop.
 The outcome is dictated by the size and location of the lesion.

26. 3. Intrauterine infection in general is one of the major causes of
congenital brain lesions.
 cyto-megalovirus (CMV) infection affecting the brain may present with a
wide range of intracranial abnormalities, including periventricular and
intraparenchymal echogenicity, ventriculomegaly, cerebellar hypoplasia,
microcephaly and cortical abnormalities.
 The most specific findings include an echogenic periventricular halo and
septations within the occipital horns.

27. VI. Microcephaly
 Microcephaly indicates the association of abnormal
neurologic development and a small head.
 Prevalence: 1 in 1,000 births.
80% of affected infants have a normal HC at birth and 90% of
affected individuals had a normal HC in the 2nd trimester.

28.  Ultrasound diagnosis is made usually in the late 2nd and 3rd trimesters.
The fetal HC/AC ratio is below the 3rd percentile
There is slopping forehead due to the disproportion of the frontal lobes and the
face.
In most cases presenting in the 2nd trimester there is associated
holoprosencephaly or encephalocele and in those presenting in the 3rd trimester
there are abnormalities of sulcation or neuronal migration.
 Associated abnormalities:
 Chromosomal abnormalities are rare and the most common are trisomies 13, 18
and 21.
 Genetic syndromes are very common. The most common are: Meckel-Gruber,
Walker-Walburg, Miller-Diecker, Smith-Lemli-Opitz, Seckel syndrome.

29.  Investigations: Detailed ultrasound examination, karyotyping and array,
TORCH test .
 Fetal brain MRI at ≥32 weeks’ gestation for diagnosis of abnormalities of
neuronal migration, such as lissencephaly and polymicrogyria.
 Follow up: US every 4 weeks for monitoring of the evolution of HC
 Prognosis:
Isolated: the risk of neurodevelopmental delay inreases with decreasing
head circumference from 10% to 100%.
Syndromic: the prognosis depends on the underlying condition.
 Recurrence:
 No associated structural defects: 5-10%.
 Familial form of isolated microcephaly: 25%.

30. VII. Intracranial cysts and tumors
 1. Intracranial arachnoid cysts are accumulations of clear cerebrospinal-
like fluid between the dura and the brain substance, but term is
frequently used to indicate any intracranial cyst located in the
subarachnoid space.

31.  They may be found anywhere in the CNS, including the spinal canal.
 They should be differentiated from other cystic lesions with different
prognostic implications, and the most important clue is that they are
external to the hemispheres.
 They may be asymptomatic, but they may cause epilepsy, mild motor or
sensory abnormalities, or hydrocephalus.
 The prognosis is good with the absence of symptoms in more than 70% of
cases.
 Large and compressing cyst: surgery is required to prevent long term
sequelae, including seizures, headache, motor deficit or
neurodevelopmental delay.

32.  2. Choroid plexus cysts: round sonolucent areas in the context of the
choroid plexus of lateral ventricles, which are found in 1–3% of
midtrimester fetuses.
 Ultrasound diagnosis: Single or multiple cystic areas (>2 mm) in one or
both choroid plexuses of the lateral cerebral ventricles.
 More than 90% resolve by 26 weeks.
 They are associated with increased risk for trisomy 18 and possibly trisomy
21.
 Investigations:
 In the absence of other markers of trisomy 18 or 21 ,
there is no need for invasive testing.
 Prognosis: Good

33.  3. Fetal intracranial tumors rare, with about 3–4 cases per million live
births.
 Teratomas account for most cases.
 the remaining minority: neuroepithelial tumors, lipomas and
craniopharyngiomas.
 Ultrasound have ussually a similar appearance (a complex mass
distorting the brain architecture, possibly associated with
macrocephaly, ventriculomegaly and intracranial calcifications)and will
rarely allow a specific diagnosis.
Only intracranial lipomas and choroid plexus papillomas have a specific
sonographic appearance.

34.  The prognosis of congenital tumors is poor with a mortality rate in the
range of 75%.
The degree of neurologic impairment in survivors is also expected to be
high.
 Intracranial lipomas represent an exception, in that the survival rate is
100% and the developmental handicap rare.
4. Tuberous sclerosis is a syndrome featured by multiorgan involvement
transmitted as an autosomal dominant trait, but frequently arising from a
spontaneous mutation.
 Mental retardation is present in 50–80% of cases and appears to be more
frequent when the diagnosis is made prenatally or in early infancy.

35.  brain lesions are the tubers, nodules of variable size and glial cells
disseminated in the neural plate or periventricular area. However, these
are extremely difficult to identify antenatally.
The condition is usually suspected when cardiac tumors are identified.
About 90% of these tumors are rabdomyoma and about 75% of these
fetuses will be affected by tuberous sclerosis.
Therefore, whenever cardiac tumors, particularly multiple ones, are
identified, a search for cerebral lesions is warranted.
MRI is generally considered to be more accurate for diagnosis.

36. VIII. Vascular abnormalities
 Vascular anomalies of the fetal brain are rare. The vein of Galen vascular
malformations is the most seen.
1. aneurysm of the vein of Galen spectrum of arteriovenous malformations,
ranging from a single large aneurysmal dilatation to multiple communications
between the vein and the carotid and vertebrobasilar systems.
 The typical finding is an elongated anechoic area,
with color and pulsed Doppler evidence of
turbulent venous and/or arterial blood flow.
 The cerebral architecture may be intact
or it may be distorted.

37.  Large arterio-venous shunts may result in high-output heart failure and
hydrops.
 Prognosis: The mortality rate is in the range of 50%, and a normal
development in about 50% of survivors.
However, the outcome is strongly dependent upon the antenatal evidence
of other intracranial and/or hydrops.
It may be difficult to distinguish an aneurysm of the vein of Galen from a
pial arteriovenous malformation.
However, the outcome is similar, and the prognosis is poor when associated
abnormal cerebral findings or signs of cardiac overload are found .

38. 2. thromobosis of the dural sinuses have been described.
 The sonographic findings are typical: enlarged sinuses and usually an
echogenic core, probably representing the thrombus.
 Thrombophilias may be found as etiology , but usually the condition is
an idiopathic one.
 Despite that the intrauterine appearance may be quite dramatic,
complete remission is frequent.
 Indeed, if there are no signs of cerebral compromise, the outcome is
good.

39. IX. Cortical malformations
 Cortical malformations are characterized by the incomplete formation of the
cortical layers, with abnormal locations of neurons that have failed to reach
their final destination.
 The migrational process may be arrested by environmental factors (ischemia,
teratogens), but a genetic predisposition is present for some anomalies.
 Macroscopically, the main finding is an alteration in the convolutional pattern of
the brain, which may be associated with modifications in brain mass and size of
the ventricles.

40.  The technique of choice for the diagnosis of these anomalies postnatally
is MRI because it allows a clear discrimination between white and gray
matter.

41. Conclusion
 When abnormal fetal cerebral anatomy is identified, counseling the parents
regarding sensible obstetric management is exceedingly difficult.
 Some cerebral anomalies have outcomes that can be predicted with reasonable
precision. However, a large number of conditions that can be accurately
identified in utero have an unclear natural history and a wide range of long-term
outcomes.
 MRI is often helpful
 multidisciplinary counseling involving pediatric neurologists and neurosurgeons,
and clinical genetics does represent a gold standard that most tertiary fetal
medicine teams should strive to provide.

42. REFERENCES
 Fetal medicine by kumar bidyut and Zarko alfirevic
 Fetal medicine foundation
 Ultrasound for fetal congenital anomalies 2nd edition by
Dario paladini and paolo volpe ,Italy 2014