Neuropsychological status in children with agenesis of corpus callosum

1. Neuropsychological status in children with agenesis of corpus callosum P. Martelli 1, E. Fazzi1,2, C. Guuva2, S. Micheletti1,3, L. Pinelli4, C. Ambrosi 4, C. Groli5, P. Moretti5, P. Accorsi 1 1UnitofChildNeurology and Psychiatry, Brescia, Italy 2DepartmentofClinical and ExperimentalSciences, UnitofChildNeurology and Psychiatry, Spedali Civili, Universityof Brescia, Brescia, Italy 3CognitionPsychologyNeuroscienceLab., Universityof Pavia, Pavia, Italy 4NeuroradiologyUnit, DepartmentofDiagnosticImaging, Universityof Brescia, Brescia, Italy 5 Prenatal DiagnosisUnit, DepartmentofObstetrics and Gynecology, Universityof Brescia,Brescia, Italy

2. Introduction The agenesis of corpus callosum (ACC) is the most frequent commissural malformation of the central nervous system. The prevalence of ACC (complete and partial) is reported to be 1.4 per 10,000 live births (California Birth Defect Minitoring Program Santo S.- Ultrasound Obstet Gynecol -2012) but 2-3% in neuropaediatric population. ACC can be isolated (absence of other extraneurological and neurological abnomalities observed by postnatal MRI, normal karyotype testing and normal virus screening) or complex (associated with other cerebral and extracerebral abnormalities, including genetic syndromes, cromosomal anomalities, viral infection or toxic syndromes).

3. ISOLATED AGENESIS of CORPUS CALLOSUM Fetal MRI(31.3 w)

4. ISOLATED AGENESIS of CORPUS CALLOSUM DTI (FA map) Post-natal MRI (6 days old)

5. AGENESIS of CORPUS CALLOSUM WITH INTEREMISPHERIC CYSTS + PMG Fetal MRI(27 w)

6. AGENESIS of CORPUS CALLOSUM WITH INTEREMISPHERIC CYSTS + PMG Post-natal MRI (2 days old)

7. Acc: state of art • The prenatal diagnosis agenesis of corpus callosum is a problem within parental counseling due to its uncertain prognosis • Prenatal counseling is currently based on scattered data coming mainly from small cases series. • In most studies assessment was made in preschool period and/or it represented only an evaluation of DQ/IQ.

8. Few studies • Most studies report a small number of cases • Imaging protocol different : prenatal diagnosis by echography or by fetal MRI; postnatal diagnosis by TC or MRI • Different terminology about complex or isolated ( f.e.: ACC isolated with interemisferic cystis) • Incomplete studies: studies not provide karyotyping information • Many study report short follow-up • Outcome assess by different tool: formal assessment with standardized and validated tool or informal assessment , interviews, non standardized questonnaires, … • Lack of distinction on the severity of neurodevelopmental delay

9. Prevalence of associated brain abnormalities is 45,8% • RMI allows direct visualization of C.C ( false-positive by ultrasound 0%-20%) and confirm whether partial or complete detect coexisting brain abnormalities (additional abnormalities in 22,5% of cases compared with ultrasonography) • The overall rate of chromosomal abnormality is 17,8% but a recent study suggests that this high risk of chromosomal abnormalities is confined to complex cases also the comparative genomic hybridization shold be considered • ACC has been associated with several syndromes AD, AR, X-linked. Bedeschi found that 33% had a recognizable syndrome. Schell-Apacik 12% • ACC has been reported in association with CMV,TOXO,rubella, influenza but other associated anomalies usually coexist • Prognosis in ACC is dependent on the coexistence of other abnormalities, which can only be assessed with advancing gestation • In 15,1% of cases thought to be isolated prenatally were found to have associated abnormalitie after birth • The rate of neurodevelopmental delay in infant with a prenatal diagnosis of isolated ACC is about 25-30% and this appears to be similar in complete and partial ACC.

10. Acc: state of art The prenatal diagnosis agenesis of corpus callosum is a problems within parental counseling due to its uncertain prognosis Prenatal counseling is currently based on scattered data coming mainly from small cases series. In most studies assessment was made in preschool period and/or it represented only an evaluation of DQ/IQ. One study has a long follow-up, neuropsychological tests, school achievement

11. Follow-up yearly until 6 years of age and every 2 years there after IQ ( Weschler Intelligence Scale for children WISC III) Laterality, short-term memory, Long-term memory, Fine motor skills, perception, analysis and synthesis of complex visual-spatial material and visual memory Cultural status of parents Information regarding school placement was collected from interviews with the parents

12. Aim of our study To describe neurodevelopmental profile in a sample of children with prenatal diagnosis of ACC

13. Study Between 1998 and 2011, 38 children were referred to Unit of Child Neurology and Psychiatry of Spedali Civili, Brescia after prenatal diagnosis of ACC. Prenatal diagnosis was made, in Prenatal Diagnosis Unit of Spedali Civili, by ultrasound between 20 w and 36 w of gestation and confirmed by fetal MRI only in 31 fetuses.

14. 38 childrenwithprenataldiagnosisof ACC 30 withpostnatal MRI 8withoutpostnatal RMI • 15 isolated ACC • 2 drop-out • 1died in car crash • 3 “normal” • (interview by phone) • - 14 complex ACC ( withassociatedcerebralanomalies and 1Aicardisyndrome) 1Otherdiagnosis 23 childrenevalueted in thisstudy 9isolated ACC 14 complex ACC

15. Characteristics of the sample INCLUSION CRITERIA: PRENATAL DIAGNOSIS OF ACC BY FETAL ULTRASOUND OR FETAL MRI FROM 1998 TO 2011 , POSTNATAL MRI, NEUROLOGICAL FOLLOW UP OF AT LEAST 18 MONTHS

16. METHODS CLINICAL , NEUROLOGICAL EVALUTION and postnatal MRI , KARYOTYPE and VIRUS SCEENING ONE NEUROPSYCHOLOGIST IN BLIND

17. outcome

18. COMPLEX ACC

20. COMPLEX ACC outcome NORMAL OUTCOME MILD IMPAIRMENT PATHOLOGICAL OUTCOME

21. OUTCOME/ POSTNATAL MRI NORMAL OUTCOME MILD IMPAIRMENT PATHOLOGICAL OUTCOME

22. COMPLEX ACC COGNITIVE ABILITIES

23. ISOLATED ACC

25. ISOLATED ACC COGNITIVE ABILITIES

26. ISOLATED ACCCOORDINATION ABILITIES

27. ISOLATED ACCATTENTIONAL PROBLEMS

28. ISOLATED ACCNEURODEVELOPMENTAL OUTCOME SHORT TERM OUTCOME (<4 years) MEDIUM TERM (4-6 years) LONG TERM (> 6 years)

29. Neuropsychological performances between -1 sd and -2 sd and/or behavioral problems (CBCL>60 T Scores)

30. CONCLUSION • The outcome of complex ACC is pathological in half of cases and depending on the underlying pathology. But we find a unexpected normal outcome in 46% of cases. • The outcome of isolated ACC, although this study has wide range ( 18 months- 15 years), confirms a normal outcome in 89% of cases. The severe outcome is evident in the first year of life

31. CONCLUSION • Neuropsychological outcome of isolated ACC children is normal only in 56% of cases. • We show a association among problems in motor coordination, in attention and in executive functions. • The “mild impairment” emerges later. • No children have an adapted school program

32. OPEN QUESTIONS • WE NEED SOME PROSPECTIVE RESEARCH WITH A LONG FOLLOW-UP AND COMPLETE NEUROPSICHOLOGICAL ASSESSMENT FOR A GOOD PRE AND POSTNATAL COUNSELING ABOUT ACC, ESPECIALLY IN ISOLATED ACC • WE NEED TO IMPROVE DEFINITION OF MILD IMPAIRMENT (NEUROPSYCHOLOGICAL ASSESSMENT MAY HAVE A MAJOR ROLE IN THE DEFINITION OF THE OUTCOME?) • THE ROLE OF TRACTOGRAPHY AND DTI- MRI : A NEW COUNSELING STRATEGY?