The corpus callosum (CC) is the largest brain interhemispheric commissure consisting of white matter. It is therefore involved in many neurologic and systemic pathologies, including congenital diseases, vascular anomalies, and white-matter diseases and tumors.12 Thinning of the CC is well described3 as resulting from either developmental anomalies or injurious diseases, such as ischemia/hypoxia. In contrast, a thickened CC is considered a rare disorder, which is described mainly in fetuses and generally considered an ominous sign at that stage of development.4567 Pashaj et al.8 constructed reference charts for measurements of the fetal CC, but these have been much less established in infants and children. Our experience led us to that a thickened CC is not that rare, and that it is not by itself a sign of an ominous disease.

In the present study we looked at children who were considered to have a thick corpus callosum (TCC) in magnetic resonance imaging (MRI) images, looking specifically for the associated clinical disorders and for potential additional brain malformations. We then measured the CC width in specific regions and compared our findings with the findings for normal CCs, in order to examine the agreement between the observation-based diagnosis of TCC and objective measurements. Our working hypothesis was that for routine clinical purposes, exact measurements of the CC thickness are not superior to observatory clinical evaluations.

The hospital Helsinki Committee (IRB) approved the study. MRI images were collected from the archived reports of the weekly neurology/radiology rounds of the hospital pediatric neurology team led by a senior neuroradiologist. The MRI images were reviewed before and during the rounds with the aim of re-evaluating the recorded findings, and the final conclusions of the discussed MRI images were summarized in a dedicated registry. We were able to retrieve the results of the re-evaluated studies as at January 2003. All of the MRI images in which the CCs were considered as being abnormally thick by the senior radiologist were reviewed by considering both clinical observations and comparison with the figures in the article by Suganthy et al.9 to confirm the initial judgement of the abnormality of the CC thickness. Imaging studies in which the CC was considered to be distorted were excluded from the study. The CC was measured in millimeters, and the pertinent clinical data of the children that had led to performing brain MRI were summarized.

The CC was measured in each brain MRI image as described by Suganthy et al.9 A paramedian sagittal section of the brain MRI was selected, and the CC was measured in the following four regions:

The measurements were performed by A.S. and O.K., and the measured values were analyzed statistically.

The reports of brain MRI investigations performed during the study period were identified, with TCC being detected in 34 children. Thus, the prevalence of a TCC in this population was 1.3% (Table 1). The average age of these children during the study period was 12.3 years, and 19 were males (54%) and 15 (46%) were females.

In the following study we investigated the frequency of a thick corpus callosum in children, diagnosed by revised observational determination by an experienced neuro-radiologist. This overall frequency was found to be 1.3%.

No specific major neurologic disorder that could be associated with the TCC was detected. It can be suggested that being asymptomatic leads to under-diagnosis of this lesion. Several factors probably also influence its low prevalence. It could be due to the lack of precise criteria to define the corpus callosum as really thick in children or due to relatively low awareness of its existence. Thus, children with a TCC can go undiagnosed or even be misdiagnosed.

In our study, the CC was defined as thick based on judgement of a neuroradiologist. This diagnostic approach can be biased by the radiologists subjective personal characteristics. Nevertheless, it can be presumed it provided a close number, due to the large total number of children, from whom those with thick CC incidence was extrapolated. We should also mention that in some cases different measurement methodologies were found to produce discordant results.12

Out of a total population of 250 children with NF-1 who were being followed at Schneider Children's Medical Center of Israel, 13 had confirmed TCCs on their brain MRI images, yielding an estimated frequency of 5%; this suggests that the prevalence of a TCC is about threefold higher in NF-1 than in the general population. The CC continues to grow until adolescence, after which it is believed to diminish slightly in size.1113 However, our children were unique in exhibiting high WG, WS, and WT values (Table 3), meaning that the CC was very thick.

We were unable to clearly delineate any mechanism underlying the increased thickness of the CC associated with a variety of pathologies that do not have a common pathogenesis. This finding is also known pathologic processes affecting the brain in NF-11415 as well as in MCM,16 but not the pathogeneses of the other conditions our study children. Given that a TCC is rare in epilepsy and is not correlated with any specific pattern of seizures, it is reasonable to consider that the CC, which is composed of white matter, plays no significant role in epileptogenesis. Indeed, the finding of a CC was not associated with specific disorders of the white matter in any members of our pediatric population. Finally, our literature search yielded no description of a CC in ASD patients, but rather evidence of a smaller CC.171819

Contrary to most reports in the literature that claim that a TCC usually involves a grave prognosis, mental retardation, and/or serious developmental delay,202123 our results consistently excluded its specific association with a serious prognosis. Of course, the prognosis in an individual patient is dependent upon the underlying condition with which the thick CC was described, and one cannot infer from our cases that a TCC is a prognosis-determining feature. Nevertheless, most of our study children (mainly in those with NF-1, nonsyndromic epilepsy, and the group of other pathologies attend normal schools and do not suffer from any major disability in their daily life, in direct contrast to another study of an NF-1 population which concluded that an enlarged CC is associated with cognitive impairment.24

We found a relatively high proportion of cases with a Chiari-1 malformation or low positioning of the cerebellar tonsils, i.e., 6 out of 35 children (17%, mainly in the MCM and NF-1 groups), one-half of whom were not macrocephalic.

Lastly, in none of our children an abnormal CC was detected prenatally in routine studies. It in our impression that a TCC may be a TCC a postnatally acquired anomaly. We recommend that the generation of more data on CC measurements to refine our understanding of its involvement in pathologic processes.

In conclusion, it seems that a TCC can be found in children with various diagnoses, especially NF-1 and MCM. We were unable to relate any specific abnormal clinical finding to its existence. However, in some children it was associated with a Chiari-1 malformation. More studies are required to better define this presentation of TCC.