Impact of maternal topiramate ingestion on ossification of skull and appendicular bones in rat fetuses.

The skull and appendicular bones are derived from different embryological sources during their development. The impact of prenatal exposure of topiramate on ossification of these bones is not adequately studied. The goal of this study was to assess the ossification patterns of the craniofacial bones and bones of the forelimbs and hindlimbs in 20-day-old rat fetuses after maternal exposure to topiramate at doses equivalent to human therapeutic doses. Three groups of Sprague-Dawley pregnant rats were used: control, topiramate 50mg/kg/day (T50) and topiramate 100mg/kg/day (T100). Topiramate was given by oral gavage from day 6 to day19 of gestation. Ossification was evaluated in the bones of 20 days fetuses after staining with Alizarin red. Results showed a significant reduction in complete ossified centers of the metacarpal, metatarsal and craniofacial bones in topiramate-exposed fetuses at both doses when compared to the control group. Also, a significant decrease in the length of ossified part of the long bones of the forelimbs and hindlimbs in topiramate-exposed fetuses at both doses was noted when compared to the control group. Crown-rump length and fetal weight were significantly decreased in topiramate treated groups compared to the control group. In all examined groups, there was a positive correlation between the crown-rump length and the lengths of humerus and femur. No abnormalities in the ossified bones and no significant changes in their ossification pattern were observed between the treated groups. In conclusion, prenatal administration of topiramate in doses equivalent to human therapeutic doses delayed ossification and development of craniofacial and appendicular bones in rat fetuses and their effects are not dose dependent at doses investigated. The implications of these findings in women who require topiramate therapy in pregnancy merit further evaluation.

Anatomical variation of sciatic nerve division in the popliteal fossa and its implication in popliteal nerve blockade.

The sciatic nerve (SN) originates from the L4-S3 roots in the form of two nerve trunks: the tibial nerve (TN) and the common peroneal nerve (CPN). The TN and CPN are encompassed by a single epineural sheath and eventually separate (divide) in the popliteal fossa. This division of the SN occurs at a variable level above the knee and may account for frequent failures reported with the popliteal block. We studied the level of division of the SN in the popliteal fossa and its relationship to the common epineural sheath of the SN. The level of division of the SN sheath into TN and CPN above the knee was measured in 30 cadaver specimens. The SN was invariably formed of independent trunks (TN and CPN) encompassed in one common epineural sheath. The SN divided at a distance range of 50 to 180 mm above the popliteal fossa crease. The present findings suggest that the TN and CPN leave the common SN sheath at variable distances from the popliteal crease. This finding and the relationship of the TN and CPN sheaths may have significant implications for popliteal nerve block.