Anatomic Variation of the Superficial Temporal Artery and Posterior Auricular Artery in a Pediatric Moyamoya Disease Population.

BACKGROUND AND PURPOSE: In certain cases of pediatric patients with Moyamoya disease undergoing encephaloduroarteriosynangiosis (EDAS) treatment, the posterior auricular artery can be used as an alternative when the parietal branch of the superficial temporal artery is unavailable. In this study, anatomic variations of the superficial temporal and posterior auricular arteries in pediatric patients with Moyamoya disease and postoperative outcomes of posterior auricular artery-EDAS are explored. MATERIALS AND METHODS: Medical records of 572 patients with Moyamoya disease who underwent surgical procedures from 2007 to 2017 at the Seoul National University Children's Hospital were reviewed. Anatomic classifications of the superficial temporal and posterior auricular arteries were based on previous classifications. Postoperative hemodynamic changes of posterior auricular artery-EDAS were analyzed using the Matsushima grade. Also, Karnofsky Performance Scale and mRS scores of posterior auricular artery-EDAS cases were reviewed to identify postoperative clinical outcomes. RESULTS: Among 1144 hemispheres, 24 were considered posterior auricular artery-EDAS candidates (2.1%). Of those, 10 hemispheres underwent posterior auricular artery-EDAS (41.7%, in total hemispheres 0.9%). Comparing the Matsushima grades of the superficial temporal artery-EDAS and posterior auricular artery-EDAS groups showed similar postoperative revascularization. Postoperative Karnofsky Performance Scale and mRS scores of patients having undergone posterior auricular artery-EDAS did not show deterioration. CONCLUSIONS: In approximately 2% of pediatric patients with Moyamoya disease for whom the superficial temporal artery is unavailable as the EDAS donor, the posterior auricular artery can be considered an alternative. On the basis of the results, the clinical outcome of posterior auricular artery-EDAS was not inferior to that of superficial temporal artery-EDAS. Hence, we suggest an in-depth consideration of the posterior auricular artery as the donor artery if the superficial temporal artery parietal branch is unavailable.

Clinically applicable human adipose tissue-derived mesenchymal stem cells delivering therapeutic genes to brainstem gliomas.

Pediatric brainstem glioma is an incurable malignancy because of its inoperability. As a result of their extensive tropism toward cancer and the possibility of autologous transplantation, human adipose-derived mesenchymal stem cells (hAT-MSC) are attractive vehicles to deliver therapeutic genes to brainstem gliomas. In this study, in a good manufacturing practice (GMP) facility, we established clinically applicable hAT-MSCs expressing therapeutic genes and investigated their therapeutic efficacy against brainstem glioma in mice. For feasible clinical applications, (1) primary hAT-MSCs were cultured from human subcutaneous fat to make autologous transplantation possible, (2) hAT-MSCs were genetically engineered to express carboxyl esterase (CE) and (3) a secreted form of the tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) expression vector for synergistic effects was delivered by a gene transfer technology that did not result in genomic integration of the vector. (4) Human CE and sTRAIL sequences were utilized to avoid immunological side effects. The hAT-MSCs expressing CE±sTRAIL showed significant therapeutic effects against brainstem gliomas in vitro and in vivo. However, the simultaneous expression of CE and sTRAIL had no synergistic effects in vivo. The results indicate that non-viral transient single sTRAIL gene transfer to autologous hAT-MSCs is a clinically applicable stem cell-based gene therapy for brainstem gliomas in terms of therapeutic effects and safety.

Therapeutic targeting of subdural medulloblastomas using human neural stem cells expressing carboxylesterase.

The prognosis of medulloblastoma has improved significantly because of advances in multi-modal treatments; however, metastasis remains one of the prognostic factors for a poor outcome and is usually associated with tumor recurrence. We evaluated the migratory potential and therapeutic efficacy of genetically engineered human neural stem cells (NSCs) that encode a prodrug enzyme in the subdural medulloblastoma model. We genetically modified HB1.F3 (F3) immortalized human NSCs to express rabbit carboxylesterase (rCE) enzyme, which efficiently converts the prodrug CPT-11 (Irinotecan) into an active anti-cancer agent (SN-38). To simulate clinical metastatic medulloblastomas, we implanted human medulloblastoma cells into the subdural spaces of nude mice. rCE expressing NSCs (F3.rCE) were labeled with fluorescence magnetic nanoparticle for in vivo imaging. The therapeutic potential of F3.rCE was confirmed using a mouse subdural medulloblastoma model. The majority of intravenously (i.v.) injected, F3.rCE cells migrated to the subdural medulloblastoma site and a small number of F3.rCE cells were found in the lungs, pancreas, kidney and liver. Animals that received F3.rCE cells in combination with prodrug CPT-11 survived significantly longer (median survival: 142 days) than control mice that received F3.rCE cells only (median survival: 80 days, P<0.001) or CPT-11 only (median survival: 118 days, P<0.001). In conclusion, i.v. injected F3.rCE NSCs were able to target subdural medulloblastomas and demonstrate therapeutic efficacy. Our study provides data that supports further investigation of stem-cell-based gene therapy against metastatic medulloblastomas.

Temporal lobe epilepsy caused by choroid plexus papilloma in the temporal horn.

Choroid plexus papilloma (CPP) arising in the temporal horn is rare in adult population, and to the best of our knowledge, there has been no report of such a case with temporal lobe epilepsy (TLE). The authors describe a unique case of a 27-year-old woman who was diagnosed as TLE and was found to have a CPP in the temporal horn. Choroid plexus papilloma of the temporal horn, even though rare, can be found in adult population and be causally related to temporal lobe epilepsy.