Agenesis of corpus callosum

1. -
CASE PRESENTATION ON AGENESIS OF CORPUS
CALLOSUM
MODERATOR - SHAMBEL (MD, OBGY FINAL YEAR RESIDENT)
PRESENTER - FASIL Y (MD, OBGY 2nd YEAR RESIDENT)

2. ilan-e-timor-tritsch, MD

3. Outline
• Objectives
• Case Summary
• Discussion
• Comments
• References

4. Objective
• To use the case as entry point and to discuss on management of fetal
ACC
• To continue the rewarding management, learn from possible pitfalls
and have common understanding on management of similar cases
subsequently
• To be familiar with neurosonographic evaluation of ACC for
prognostication and counseling of similar cases for the future

5. Summary of the case
Identification
• MRN - 763677
• Name - S.T
• Age - 31
• Address - Gondar K. 03
• Marital Status - Married
• Occupation -House Wife
• Date of admission - 19/12/13E.C

6. Anatomic scan- 22/10/13 at 32W3D
•Singlton, cephalic
•GA by BPD, HC-36 wk; TCD-29W6D; AC &FL-31W6D
•There is Lt venticulomegally (19mm) with colpocephaly
•CSP & part of CC seen on brain axial view
•Difficult to visualize CC on sagital view with both 2D &PD
•No midline or posterior fossa defect
•CVS,GZ,MSS appear normal
•Mild left kidney hydronephrosis-8.9 mm
INDEX - 3rd TM Px + ?CC agenesis + mildleft kidney hydronephrosis
PLAN - fetal brain MRI & counseling of the mother

7. Pre and Post contrast Brain MRI-25/10/13
• There is no well visualized
corpus callosum with paralleling
of the anterior horns of the
lateral ventricles and
disproportinate enlargment of
the occipital horns and atria
Conclusion - Corpus Callosum
Agenesis

8. History on 19/12/13 ec
• 31 years old G IV PII (both alive) and I SA mother
• GA-40 Wks (13W and 3D US)
• ANC- at Private clinic and GUH
BG & RH-B+
NR for RVI & VDRL
•1st delivery 11 yrs back- told to have a form of anomaly in the CNS and
alive but have difficulty in communication
•2nd pregnancy- spontaneous abortion at 3 month of px
•3rd delivery 3 years back- uneventful

9. Physical Examination
• GA- Comfortable
• V/S- BP-100/60 mmhg PR-84 RR-22 T-36.8OC
• HEENT -pink & non icteric sclera
• LGS - no LAP
• CHEST - clear & resonant
• CVS - S1& S2 well heard
• ABD - Term sized gravid uterus
• lontudinal lie , cephalic ,no tenderness or contraction
• FHB -148

10. .
• GUS - no CVAT
• Cx-closed,posterior,uneffaced,firm in consistency,station -1
• IGS - no pallor
• MSS - no edema
• CNS - conscious & oriented

11. obs US by consultant- 19/12/13
• Singlton, cephalic, FHB - +ve
• AGA - 38 W, EFW - 3680 gm, HC - 34 cm
• Fundal Placenta , AFI - 2.5 cm
• GBM, FT,FBM sen
• CNS - colpocephaly with unilateral ventriculomegally (LT=23 mm)
 On midsagital view- difficult to appreciate the whole segment of CC
and difficult to visualize pericallosal vessels on CF
• Renal- left moderate hydronephrosis
INDEX 3rd TM px + Agenesis of CC + Lt moderate hydronephrosis +
Oligohydraminos
PLAN- Admit for Induction

12. Done
• Admitted to maternity ward
• Cervix ripened with transcervical foley catheter
• Induction started per protocol and followed ??
• Emergency CS was done for the indication of Failed Induction -
3.5 kg M neonate with 8&9 APGAR score
•Neonate transfered to NICU for evaluation

13. Admission NST

14. Induction followup ?

15. Discharge Summary 23/12/13
• A 31 yrs old PIII 1 SA mother on her 2nd post op day after ETLUS CS
was done for the indication of Failed Induction to effect in the
delivery of a 3.5 kg male alive neonate with 8&9 APGAR score after
she was admmited with the diagnosis of full term px +
oligohydraminos + ACC + unfavorable bishop score
• GA- comfortable, Stable vital sign
•Post op HCT - 34%
• Good Post OP condition
• PLAN-advice on contraceptive, sunlight exposure, EBF, danger signs
link the neonate to PEDI side for furthur evaluation

16. Year 1 Resident Neonatal Evaluation at NICU 21/12/13
• This is a 1hr M alive neonate born to a 31 yrs old PIII mother
• Told to have fetal ACC by perinatal US of the fetus
• Labor onset is by induction with a total duration of labor 16 hrs and
duration of ROM of 8 hrs
• Mode of delvery was via CS for failed induction to effect in the
delivery of 3.5 kg M with 8&9 APGAR score

17. • VS- AHR-146 RR-44 T-36.8 WT - 3500gm L- 54cm HC-37cm → AGA
• HEENT-pink conj & NIS
deformed and low seated ear
•LGS - well formed breast buds
•CHEST- good air entry, no SC or IC retraction
•GUS - there is ureatheral opening on the ventral
part of penis near the scrotum
•MSS - Rocker Bottom Feet
ASST- Edward Syndrome + Hypospadiasis
PLAN- CBC, BG, RBS, RFT, Trans fontanel US, Abd US, ECHO,
Consult surical side

18. • CBC -
• RFT - Normal
• RBS -
• Abd US ??
• Trans fontanel US & Echo?
• Linked to physiotherapy

20. Agenesis of the Corpus Callosum

21. Corpus Callosum:
• Major interhemispheric bundle
of commissural fibers in the
brain that allows the transfer of
motor, sensory, and cognitive
information between the two
hemispheres
• Contain about 200 million axons
that connect the left and right
cerebral hemisphere
• It is one of the five main cerebral
commissures
• Consist approximately 2–3% of
all cortical fibers
• Unique to placental mammals

22. Traditionally been divided
into four anatomically
defined regions:
The genum, rostrum, body
(divided into anterior,
middle, and posterior
segments), and the
splenium

23. • It appears by the 10th week of development and connects the
nonolfactory areas of the right and the left cerebral cortices
• First appears in the genu region at, and follows a cranio‐caudal
progression
• The anterior part of the rostrum appears last
• By 18–22 weeks the final shape of the CC is apparent on imaging
although further thickening occurs throughout pregnancy and infancy

26. STRUCTURAL ANOMALIES OF THE CORPUS
CALLOSUM
• Malformations of corpus callosum can occur in isolation; in
association with chromosomal, syndromic, or monogenic disorders;
or, rarely, secondary to infectious, ischemic, or teratogenic causes
• Congenital structural abnormalities of the CC include:
ACC - total Vs partial
Hypoplasia - refers to a thinner CC that has a normal
anterior‐posterior extent
Dysgenesis - refers to the CC being present but malformed
Hyperplasia - which may result from reduced postnatal axonal
pruning

28. PREVALENCE
• Among live births, the reported prevalence is 1.8: 10,000.
• In children with developmental disabilities, it is 2 : 100 to 3 :100, and
• In patients with an existing CNS anomaly, it is 47 :100

29. ETIOLOGY
• Approximately 30%-45% have an identifiable cause
• The most frequent causes of corpus callosum agenesis (ACC) are gene
mutations
• 10%-17% have chromosomal anomalies such as deletions, trisomies
(13, 18, 21), and duplications
• 20%-35% have recognizable genetic syndromes such as Anderman,
L1CAM, and Aicardi
• Fetal alcohol syndrome (FAS) is the most important non-genetic
congenital cause of ACC, with an incidence of approximately 7% in
FAS cases

31. Possible causes include:
1. Chromosomal (genetic) abnormalities (e.g, trisomy 8 and 18, Andermann
syndrome )
2. Prenatal infections or viruses (e.g, rubella)
3. Exposure to certain medications ( e.g, valproate, an epilepsy medication )
4. Toxic metabolic conditions (e.g, Fetal Alcohol Syndrome)
5. Blockage of the growth of the corpus callosum (e.g , cysts)
6. Metabolic disorders
7. Other unknown factors

32. Diagnosis of ACC
The diagnosis of intracranial anomalies depends on 3 important factors:
1.Accurate determination of the gestational age of the fetus,
2.Knowledge of the developmental embryology of the central nervous
system, and
3.Use of a systematic approach for the evaluation of the fetal brain.

33. BASIC EVALUATION OF THE FETAL BRAIN
• Transabdominal approach
• Used in order to screen for CNS malformations in the second and
third trimesters of gestation in low-risk patients
• Sensitivity of 80% for the detection of CNS malformations
•Conventionally, the ultrasound evaluation of brain development
during pregnancy is performed in the axial planes of the fetal skull

34. (a) Transventricular plane:
includes the lateral ventricles
(b) Transcerebellar plane:the
cerebellum and cisterna magna
are measured
(c) Transthalamic plane:measure the
BPD and HC and includes the
midline falx, cavum septum
pellucidum (CSP), and thalami

35. Transthalamic plane Transventricular plane
Transcerebellar plane

36. NEUROSONOGRAM:
1)Is often performed using transvaginal ultrasonography (if the fetus is
in a cephalic presentation) to improve imaging
2)Adds the coronal and sagittal planes
3)Uses color Doppler to clarify the nature of cystic structures or
document brain vessels
4) Adds 3-dimensional ultrasonography (if available)
•NB obtained by positioning the transducer in the cranial sutures and
fontanelles

40. Indirect US features
• Absence of the cavum septi
pellucidi,
• Colpocephaly - dilatation of the
atria and occipital horns of the
lateral ventricles
• Abnormal course of the
pericallosal artery,
• Widening of the
interhemisphere fissure, and
• Radial disposition of the sulci on
the internal aspects of the
hemispheres
In our case

42. • The definitive diagnosis of complete or partial ACC is made in the
directly acquired 2-dimensional median plane or in the median plane
of an axially acquired 3-dimensional volume
• Fetal MRI is particularly useful in the workup of isolated ACC
• Ultrasound imaging has a false positive rate of 20%
• Prenatal MRI is preferable after 22 weeks as it provides improved
detection of additional abnormal gyral patterns and heterotopia in up
to 22.5% of cases

43. • Fourteen studies (798 fetuse) were included
RESULTS
• In cases with isolated cACC, 10.9% and 4.3% of associated anomalies
were detected during fetal MRI and postnatal , respectively
• in cases with isolated pACC, 13.4% and 16.2% of associated anomalies
were detected during fetal MRI and postnatal, respectively
Conclusion: The rate of associated anomaly detected exclusively with
fetal MRI for isolated neurosonographical ACC is lower than previously
reported.

44. Associated Anomalies
CNS anomalies are seen in up to 85% of cases such as
• interhemispheric cysts, arachnoid cysts, Chiari II malformation,
migration disorders, and schizencepha
Non-CNS anomalies are seen in up to 65% of ACC cases:
• craniofacial (macrocephaly, hypertelorism, broad and depressed nasal
bridge, and cleft lip/palate),
• skeletal (hand malformations, scoliosis),
• cardiac (ventricular septal defect [VSD], patent ductus arteriosus [PDA]),
• ocular (coloboma, anopthalmia),
• genital (cryptorchism), and
• renal abnormalities (hydronephrosis)

45. • Genetic Evaluation:Chromosomal abnormalities occur in 17% of ACC
cases,and even isolated complete or partial ACC carries a 4.8% and
7.5% risk for aneuploidy, respectively
• most commonly trisomies 18 and 13 and mosaic trisomy 8
• Serologic testing for cytomegalovirus or Zika virus is rarely useful
unless suggested by other findings
• amniocentesis for CMA should be offered when ACC is detected

48. Signs and symptoms
Vary greatly among individuals
• Some characteristics common in individuals with callosal disorders include
Poor motor coordination,
Delays in motor milestones such as sitting and walking,
Delayed toilet training,
Chewing and swallowing difficulties
Vision impairments,
Hypotonia
Low perception of pain,
sometimes seizures, spasticity, early feeding difficulties

49. Management

50. OBSTETRIC MANAGEMENT
•Delivery in a tertiary care facility with access to NICU and pediatric
subspecialties is suggested
•Vaginal delivery is not contraindicated
•Cesarean delivery for obstetric indications

51. NEONATAL MANAGEMENT
• Consider ultrasound and/or MRI to better define the anomaly and to
look for associated malformations
• Consultation with genetics to exclude genetic syndrome
• Neurology and neurosurgery consultations depending on associated
anomalies

52. Prognosis
• Complete and partial ACCs associated with coexisting brain abnormalities or
genetic syndromes tend to lead to poor neurodevelopmental outcomes
• In contrast, isolated complete and partial ACCs have a better prognosis and
appear to have similar outcomes
• Normal development, in about 75% of individuals
• Borderline-moderate and severe neurodevelopmental delays are observed in
14.9% to 16.0% and 8.2% to 12.5% of isolated cases, respectively
• Epilepsy in 35%-severity depends on the presence of other CNS anomalies
• Recurrence - Isolated: 3-5%.

53. • Controlled clinical trials published between May 23, 2009, and May
23, 2019, using the term “agenesis of corpus callosum” were
reviewed
• A total of 942 articles were identified, and 8 studies were included in
the systematic review depending on the inclusion criteria
• These studies included 217 fetuses with isolated CCA and no other
anomalies at prenatal assessment
• In this review, neurodevelopment was favorable in two-thirds of the
cases (IQ>85)
• They could not determine any difference, between cCCA and pCCA,
possibly due to the small number of patients with pCCA

54. Comments
• Fetal surveilance were good with better FM foolowup;
• Timing of Neurosonography?
• Evaluation by NICU side, better to involve consultants
• Post partum investigations are incomplete
• Poor documentation by NICU side
• Proper counseling postpartally were not provided
• No surgical side evaluation for the hypospadiasis

55. Reference
• Creasy and Resnik’s Maternal-Fetal Medicine,7th ed,n2014
• Callen’s Ultrasound in Obstetrics and Gynecology, 6th ed,n2017
• Ultrasound in Obstetrics & Gynecology, a practical approach.1sted,2014
• ISUOG practice guidelines: performance of first trimester fetal ultrasound scan.
Ultrasound Obstet Gynecol 2013; 41:102-113
• American Institute of Ultrasound in Medicine practice guidelines on the performance
the obstetric ultrasound examination, 2013.
• Salomon LJ, Alfirevic Z, Brghalla C, Bilardo C, Hernandez – Andrade E, Jhonsen SL
Kalache K. Practice Guidelinefor performance of the routine mid-trimester fetal
ultrasound scan . Ultrasound Obstet Gynecol 2011;37;116-126
• Sunita Dashottar1, Krishna Pratap Singh Senger2*, Yashashvi Shukla1, Ankita Singh3,
Surabhi Sharma. Transcerebellar diameter: an effective tool in predicting gestational
age in normal and IUGR pregnancy. Int J Reprod Contracept Obstet Gynecol. 2018
Oct;7(10):4190-4196

56. THANK YOU