In view of the widely recognized correlation between extent of surgical resection and length of survival of children with intracranial ependymoma and the statement that total resection is more likely to be achieved in supratentorial than infratentorial primaries, we decided to review our experience with supratentorial ependymomas and the pertinent literature to verify the importance of surgery in treating this subgroup of pediatric ependymal neoplasms. Of 23 patients operated on, 12 are still alive without evidence of disease 72-357 months after surgery (mean 227, median 237 months). One girl treated by surgery alone was lost to follow-up after 234 months when she, and 7 other patients in the series, had already passed the end of the period of risk for recurrence according to Collins' law. Six surviving patients (2 with subependymoma and 4 with ependymoma) were treated by surgery alone and only 1, the oldest in the series, had to undergo a second operation for recurrence after 10 years. The idea of treating intracranial ependymoma by surgery alone was favored by eminent neurosurgeons in the past and has recently received renewed attention. This was in part the consequence of recognizing that unlike diffuse astrocytoma, in which neoplastic cells can be found up to several centimeters away from the apparent tumor borders, ependymoma has more or less well-defined margins and grows mainly by expansion. Early experience with the policy of electively deferring adjuvant therapy after radiologically controlled total resection of ependymoma seems encouraging, although postoperative MRI does not yet indicate absolute certainty. Close surveillance is recommended. The majority of ependymomas so far treated by surgery alone, with relatively good success, have been supratentorial. In conclusion, on the basis of our experience and a review of the literature we favor a change in attitude to the management of intracranial ependymomas, especially of the cerebrum, with radiologically controlled radical surgery alone followed by close surveillance with periodic MR imaging until the child passes the period of risk for recurrence according to Collins' law as the initial option. In children less than 3 years old the period of surveillance should be doubled. In case of recurrence, reoperation should be considered first, particularly for supratentorial primaries. Radiotherapy continues to be a major option in malignant ependymoma and unresectable primary or recurrent benign ependymoma.
A correlation between epilepsy and cellular redox imbalance has been suggested, although the mechanism by which oxidative stress (OS) can be implicated in this disorder is not clear. In the present study several oxidative stress markers and enzymes involved in OS have been determined. In particular, we examined the levels of 4-hydroxy-2-nonenal protein adducts (HNE-PA), a by-product of lipid peroxidation, and the activation of NADPH oxidase 2 (NOX2), as cellular source of superoxide (O(2)(-)), in surgically resected epileptic tissue from drug-resistant patients (N=50). In addition, we investigated whether oxidative-mediated protein damage can affect aquaporin-4 (AQP4), a water channel implicated in brain excitability and epilepsy. Results showed high levels of HNE-PA in epileptic hippocampus, in both neurons and glial cells and cytoplasmic positivity for p47(phox) and p67(phox) suggesting NOX2 activation. Interestingly, in epileptic tissue immunohistochemical localization of AQP4 was identified not only in perivascular astrocytic endfeet, but also in neurons. Nevertheless, negativity for AQP4 was observed in neurons in degeneration. Of note, HNE-mediated post-translational modifications of AQP4 were increased in epileptic tissues and double immunofluorescence clearly demonstrated co-localization of AQP4 and HNE-PA in epileptic hippocampal structures. The idea is that sudden, disorderly, and excessive neuronal discharges activates NOX2 with O(2)(-) production, leading to lipid peroxidation. The resulting generation of HNE targets AQP4, affecting water and ion balance. Therefore, we suggest that seizure induces oxidative damage as well as neuronal loss, thereby promoting neuronal hyperexcitability, also affecting water and ion balance by AQP4 modulation, and thus generating a vicious cycle.
As hypothesized by Cushing, our study shows that a large proportion of cerebellar astrocytomas do not progress or even regress after partial excision. This phenomenon is not understood and unfortunately cannot be anticipated. However, it suggests that a policy of "wait and see" with serial MR imaging can reasonably be recommended in children with cerebellar astrocytoma after partial resection, if the remnant is too risky to be removed by second-look surgery.
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