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Antenatal ultrasonographic findings differentiating complete from partial agenesis of the corpus callosum
Antenatal ultrasonographic findings differentiating complete from partial agenesis of the corpus callosum Ron Tepper~ MD, Yaron Zalel, MD, Eti Gaon, BA, Moshe Fejgin, MD, and Y. Beßh, MD Kfar-Saba, Israd Four cases of complete (three) and partia[ (one) agenesis were evaluated ultrasonographically. The frontal Iobe/biparietal diameter ratio were evaluated in 113 normal fetuses and cornpared with those ratios in fetuses with corpus callosum agenesis. In the presence of the ctassic ultrasonographic features of agenesis of the corpus callosum, frontal lobe shortening, along with absence of the cavum septi pellucidi, might contribute to the diagnosis of complete agenesis of the corpus callosum and distinguish it from partial agenesis. (AMJ OBSTETGYNECOL1996;174:877-80 Key words: Agenesis of corpus callosum, prenatal diagnosis Failure of d e v e l o p m e n t of the callosal commissure fibers c o n n e c t i n g the cerebral h e m i s p h e r e s results in complete or partial agenesis of the corpus callosum. T h e i n e i d e n c e ofagenesis of the corpus callosum ranges from 1 : 100 to 1 : 19000.' Classic ultrasonographic findings, in addition to the absence of' the corpus callosum, include splaying of the narrow and p o i n t e d frontal horns, cotpocephaly, lateral displacement of the medial walls of the anterior and posterior horns, and elevation of the dilated third ventricle, along with absence of the cavum septi pellucidi. ~ We present f o u r cases of agenesis of the corpus callosum e n c o u n t e r e d in our department, with emphasis on the nltrasonographic features, suggesting new characteristic signals that might assist in distinguishing c o m p l e t e frora partiat agenesis.
Patients Four cases of agenesis of the corpus callosum (three c o m p l e t e and one partial agenesis) were diagnosed in o u t ultrasonography unit by use of an Aloka SSD-680 (Aloka, Tokyo) with a transabdominal 3.5 MHz transducer. In two the diagnoses were m a d e during routine third-trimester ultrasonographic biophysical profile examinations, and the additional two cases were diagnosed d u r i n g ultrasonographic screening for anomalies in low-risk patients at 20 weeks' gestation. T h e m e a n age of the patients age was 25.7 years. Patients 1 and 3 were sisters-in-law. Maternal s e r u m h u m a n chorionic g o n a d o t r o p i n levels were elevated in cases Patients 9 and 4 (5.7 and 4.0 multiples of the median, respectively), whereas the rest of the s e r u m markers were within n o r m a l limits. Only patient 2 underwent amniocentesis, which revealed a n o r m a l karyotype.
From theDepargmenlof Obstet~icsand Cynecology,Sap*rMedical Ce~~te~: Receivedfor publication August 4, 1995; acceptedAugust 9, 1995. Reprint requesls; Faron ZaM, MD, Department of Obstet*ics and @necolo~y, Sapir Medical Cenler, Kfar-Saba, 44281 Israel. Copyright © 1996 by Mosby-Year Book, Inc. 0002~9378/96 $5.00+ 0 6/1/68438
T h e frontal lobe length, or the frontothalamic distance, was also evalnated in 113 n o r m a l singleton gestations from 14 to 40 weeks' gestation to collect data for a n o m o g r a m (Fig. 1). This p a r a m e t e r was measured in the axial plane from the i n n e r table of the frontal lobe to the posterior thalamus. In the cases with c o m p l e t e agenesis of the corpus callosmn, in addition to the classic ultrasonographic features, the frontal lobe was foreshortened, whereas it was n o r m a l in the case of partial agenesis. Mean (+SD) of the n o r m a l frontal i o b e / b i p a r i e t a l diameter ratio, as plotted on the n o m o g r a m (Fig. 1), slightly decreased from 82% ± 1.5% at 14 to 18 weeks' gestation to 73% _+0.5% at term (40 weeks). T h e calculated ratios of the fetuses witb c o m p l e t e agenesis of the corpus callosum, plotted on the same n o m o g r a m , are shown to be significantly <2 SD of the n o r m a l values. F u r t h e r m o r e , in all three cases with c o m p l e t e agenesis the cavum septi pellucidi could not be demonstrated, whereas it was demonstrated in the case with partial agenesis of the corpus callosum. T h e diagnosis of agenesis of the corpus callosum was c o n f i r m e d by p o s t p a r t u m ultrasonography followed by c o m p n t e d t o m o g r a p h y in three cases and in p o s t m o r t e m examination in the fetus with parfial agenesis o f the corpus callosum. A direct negative correlation was f o u n d ben«een gestational age and the frontal l o b e / b i p a r i e t a l d i a m e t e r ratio (Fig. 1) (Pearson's r = -0.8038, p < 0.000001). I,inear regression analysis showed a slope that can be calcutated by the following formula: Frontal l o b e / B i p a r i e t a l dia m e t e r = 86153 - 0:318 x Gestational week (t = 6.76, p < 0.000001). C o n f i d e n c e limits on the slope can be calculated a s - 0 . 3 1 8 ± I x 0.047.
Comment Agenesis of the corpus callosum, the white matter stn~cture that connects both cerebral hemispheres, ranges in severity f f o m m i n o r degrees of deficiency of the splenium 877
878
Tepper et al.
March 1996 AmJ Obstet Gynecol
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Fig. 1. Mean (_+SD) of frontal lobe/biparietal diameter (BPD) ratio according to gestational age in normal fetuses, and ratios in fetuses with agenesis of corpus callosum, c, Complete agenesis; p, partial agenesis.
to total failure of formation of the telencephalic commissures. An early insuh may lead to c o m p l e t e agenesis, whereas a later one will cause partial agenesis.~ T h u s , w h e n partial agenesis occurs, it usually involves the posterior caudal segment; the splenium is absent, but the anterior callosal structures (rostrum and genu) are present. Antenatal ultrasonographic diagnosis was first described by Comstock et al. ~T h e u h r a s o n o g r a p h i c features include an increased separation of the lateral ventricles, e n l a r g e m e n t of the occipital horns and atria, and upward displacement of the third ventricle, 2 features that were also d e m o n s t r a t e d in our series. Meizner et al? described an alteration or absence of the cavum septum pellucidum as an additional sign. T h e d e v e l o p m e n t of the corpus callosum is related integrally to the d e v e l o p m e n t of the septum p e l l u c i d u m and the cavum septi pellucidi, thus ultrasonographic d e m o n s t r a t i o n of the cavum septi pellucidi excludes c o m p l e t e agenesis of the corpus callosum. N o m o g r a m s of frontal lobe and frontothalamic distance were used as a potential tool for prenatal diagnosis of microcephaly and Down syndrome. As we have shown, in all three cases of c o m p l e t e agenesis of the corpus callosum we f o u n d a significantly lower frontal l o b e / b i p a r i e t a l d i a m e t e r ratio, with all values <2 SD of the n o r m a l values to their gestational week and with a m e a n of 60.1% (range 51.5% to 65%), whereas in the case of the partiaI agenesis of the corpus callosum the ratio was within normal limits (80%). We can assume, that in cases of complete agenesis of the corpus callosum, the lateral displacem e n t and dilatation of the posterior and the anterior part of the lateral ventricles causes the s h o r t e n i n g of the frontal lobe, as d e m o n s t r a t e d in o u t study. In comparison, in
partial agenesis of the corpus callosum the dilatation without the displacement of the posterior, but not the anterior, part of the lateral ventricle does not cause this shortening. Lockwood et al. 4 antenatally diagnosed partial agenesis of the corpus callosum on the basis of posterior ventriculomegaly without o t h e r signs of agenesis of the corpus callosum. We suggest that to diagnose this disorder m o r e accurately the cavum septi pellucidi should be d e m o n s t r a t e d along with a n o r m a l frontal l o b e / b i p a r i e t a l d i a m e t e r ratio. In summary, four cases of antenatal uhrasonographic diagnosis ofagenesis of the corpus callosum are described. We believe that in addition to the classic, previously described signs of agenesis of the corpus callosum complete agenesis of the corpus catlosum may be ultrasonographically distinguished from partial agenesis of the corpus callosum by the absence of cavum septi pellucidi and by the shortening of the frontal lobe. These observations deserve additional confirmation in a larger series. REFERENCES
1. Ettlinger G. Agenesis of the corpus callosum. In: Vinken GW, Bruyn PW, eds. Handbook of clinical neurology. Amsterdam: Elsevier/North Holland Bio-medical Press, 1977;30:285-97. 2. Comstock CH, Culp D, GonzalezJ, Boal DB. Agenesis of the corpus callosum in the fetus: its evolution and significance. J Ultrasound Med 1985;4:613-6. 3. Meizner I, Barki Y,, Hertzanu Y. Prenatal sonographic diagnosis of agenesis of corpus callosum. J Clin Ultrasound 1987;15: 262-4. 4. Lockwood CJ, Ghidini A, Aggarwal R, HobbinsJC..~altenatal diagnosis of partial agenes~s of the corpus callosum: a benign cause of ventriculomegaly. AM J OSSVETG~v.«oL 1988;159: 184-6.
Patients Four cases of agenesis of the corpus callosum (three c o m p l e t e and one partial agenesis) were diagnosed in o u t ultrasonography unit by use of an Aloka SSD-680 (Aloka, Tokyo) with a transabdominal 3.5 MHz transducer. In two the diagnoses were m a d e during routine third-trimester ultrasonographic biophysical profile examinations, and the additional two cases were diagnosed d u r i n g ultrasonographic screening for anomalies in low-risk patients at 20 weeks' gestation. T h e m e a n age of the patients age was 25.7 years. Patients 1 and 3 were sisters-in-law. Maternal s e r u m h u m a n chorionic g o n a d o t r o p i n levels were elevated in cases Patients 9 and 4 (5.7 and 4.0 multiples of the median, respectively), whereas the rest of the s e r u m markers were within n o r m a l limits. Only patient 2 underwent amniocentesis, which revealed a n o r m a l karyotype.
From theDepargmenlof Obstet~icsand Cynecology,Sap*rMedical Ce~~te~: Receivedfor publication August 4, 1995; acceptedAugust 9, 1995. Reprint requesls; Faron ZaM, MD, Department of Obstet*ics and @necolo~y, Sapir Medical Cenler, Kfar-Saba, 44281 Israel. Copyright © 1996 by Mosby-Year Book, Inc. 0002~9378/96 $5.00+ 0 6/1/68438
T h e frontal lobe length, or the frontothalamic distance, was also evalnated in 113 n o r m a l singleton gestations from 14 to 40 weeks' gestation to collect data for a n o m o g r a m (Fig. 1). This p a r a m e t e r was measured in the axial plane from the i n n e r table of the frontal lobe to the posterior thalamus. In the cases with c o m p l e t e agenesis of the corpus callosmn, in addition to the classic ultrasonographic features, the frontal lobe was foreshortened, whereas it was n o r m a l in the case of partial agenesis. Mean (+SD) of the n o r m a l frontal i o b e / b i p a r i e t a l diameter ratio, as plotted on the n o m o g r a m (Fig. 1), slightly decreased from 82% ± 1.5% at 14 to 18 weeks' gestation to 73% _+0.5% at term (40 weeks). T h e calculated ratios of the fetuses witb c o m p l e t e agenesis of the corpus callosum, plotted on the same n o m o g r a m , are shown to be significantly <2 SD of the n o r m a l values. F u r t h e r m o r e , in all three cases with c o m p l e t e agenesis the cavum septi pellucidi could not be demonstrated, whereas it was demonstrated in the case with partial agenesis of the corpus callosum. T h e diagnosis of agenesis of the corpus callosum was c o n f i r m e d by p o s t p a r t u m ultrasonography followed by c o m p n t e d t o m o g r a p h y in three cases and in p o s t m o r t e m examination in the fetus with parfial agenesis o f the corpus callosum. A direct negative correlation was f o u n d ben«een gestational age and the frontal l o b e / b i p a r i e t a l d i a m e t e r ratio (Fig. 1) (Pearson's r = -0.8038, p < 0.000001). I,inear regression analysis showed a slope that can be calcutated by the following formula: Frontal l o b e / B i p a r i e t a l dia m e t e r = 86153 - 0:318 x Gestational week (t = 6.76, p < 0.000001). C o n f i d e n c e limits on the slope can be calculated a s - 0 . 3 1 8 ± I x 0.047.
Comment Agenesis of the corpus callosum, the white matter stn~cture that connects both cerebral hemispheres, ranges in severity f f o m m i n o r degrees of deficiency of the splenium 877
878
Tepper et al.
March 1996 AmJ Obstet Gynecol
90 2,
85- / %
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.........
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25
27
Gestational
[
- -
Mean
......... S.D.
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31
33
35
37
39
Age (wks)
- ....... + S . D .
]
Fig. 1. Mean (_+SD) of frontal lobe/biparietal diameter (BPD) ratio according to gestational age in normal fetuses, and ratios in fetuses with agenesis of corpus callosum, c, Complete agenesis; p, partial agenesis.
to total failure of formation of the telencephalic commissures. An early insuh may lead to c o m p l e t e agenesis, whereas a later one will cause partial agenesis.~ T h u s , w h e n partial agenesis occurs, it usually involves the posterior caudal segment; the splenium is absent, but the anterior callosal structures (rostrum and genu) are present. Antenatal ultrasonographic diagnosis was first described by Comstock et al. ~T h e u h r a s o n o g r a p h i c features include an increased separation of the lateral ventricles, e n l a r g e m e n t of the occipital horns and atria, and upward displacement of the third ventricle, 2 features that were also d e m o n s t r a t e d in our series. Meizner et al? described an alteration or absence of the cavum septum pellucidum as an additional sign. T h e d e v e l o p m e n t of the corpus callosum is related integrally to the d e v e l o p m e n t of the septum p e l l u c i d u m and the cavum septi pellucidi, thus ultrasonographic d e m o n s t r a t i o n of the cavum septi pellucidi excludes c o m p l e t e agenesis of the corpus callosum. N o m o g r a m s of frontal lobe and frontothalamic distance were used as a potential tool for prenatal diagnosis of microcephaly and Down syndrome. As we have shown, in all three cases of c o m p l e t e agenesis of the corpus callosum we f o u n d a significantly lower frontal l o b e / b i p a r i e t a l d i a m e t e r ratio, with all values <2 SD of the n o r m a l values to their gestational week and with a m e a n of 60.1% (range 51.5% to 65%), whereas in the case of the partiaI agenesis of the corpus callosum the ratio was within normal limits (80%). We can assume, that in cases of complete agenesis of the corpus callosum, the lateral displacem e n t and dilatation of the posterior and the anterior part of the lateral ventricles causes the s h o r t e n i n g of the frontal lobe, as d e m o n s t r a t e d in o u t study. In comparison, in
partial agenesis of the corpus callosum the dilatation without the displacement of the posterior, but not the anterior, part of the lateral ventricle does not cause this shortening. Lockwood et al. 4 antenatally diagnosed partial agenesis of the corpus callosum on the basis of posterior ventriculomegaly without o t h e r signs of agenesis of the corpus callosum. We suggest that to diagnose this disorder m o r e accurately the cavum septi pellucidi should be d e m o n s t r a t e d along with a n o r m a l frontal l o b e / b i p a r i e t a l d i a m e t e r ratio. In summary, four cases of antenatal uhrasonographic diagnosis ofagenesis of the corpus callosum are described. We believe that in addition to the classic, previously described signs of agenesis of the corpus callosum complete agenesis of the corpus catlosum may be ultrasonographically distinguished from partial agenesis of the corpus callosum by the absence of cavum septi pellucidi and by the shortening of the frontal lobe. These observations deserve additional confirmation in a larger series. REFERENCES
1. Ettlinger G. Agenesis of the corpus callosum. In: Vinken GW, Bruyn PW, eds. Handbook of clinical neurology. Amsterdam: Elsevier/North Holland Bio-medical Press, 1977;30:285-97. 2. Comstock CH, Culp D, GonzalezJ, Boal DB. Agenesis of the corpus callosum in the fetus: its evolution and significance. J Ultrasound Med 1985;4:613-6. 3. Meizner I, Barki Y,, Hertzanu Y. Prenatal sonographic diagnosis of agenesis of corpus callosum. J Clin Ultrasound 1987;15: 262-4. 4. Lockwood CJ, Ghidini A, Aggarwal R, HobbinsJC..~altenatal diagnosis of partial agenes~s of the corpus callosum: a benign cause of ventriculomegaly. AM J OSSVETG~v.«oL 1988;159: 184-6.