Successful Treatment of Intracranial Glioblastoma Xenografts With a Monoamine Oxidase B-Activated Pro-Drug.

The last major advance in the treatment of glioblastoma multiforme (GBM) was the introduction of temozolomide in 1999. Treatment with temozolomide following surgical debulking extends survival rate compared to radiotherapy and debulking alone. However, virtually all glioblastoma patients experience disease progression within 7 to 10 months. Although many salvage treatments, including bevacizumab, rechallenge with temozolomide, and other alkylating agents, have been evaluated, none of these clearly improves survival. Monoamine oxidase B (MAOB) is highly expressed in glioblastoma cell mitochondria, and mitochondrial function is intimately tied to treatment-resistant glioblastoma progression. These glioblastoma properties provide a strong rationale for pursuing a MAOB-selective pro-drug treatment approach that, upon drug activation, targets glioblastoma mitochondria, especially mitochondrial DNA. MP-MUS is the lead compound in a family of pro-drugs designed to treat GBM that is converted into the mature, mitochondria-targeting drug, P(+)-MUS, by MAOB. We show that MP-MUS can successfully kill primary gliomas in vitro and in vivo mouse xenograft models.

Endovascular management of six simultaneous intracranial dural arteriovenous fistulas in a single patient.

A 64-year-old man with a history of traumatic brain injury 4 years previously presented with progressive cognitive decline and gait abnormality. MRI revealed diffusion restriction in the bilateral centrum semiovale and multiple serpiginous flow voids. Cerebral angiogram revealed a total of six intracranial dural arteriovenous fistulas with separate fistulas of the right and left sphenoid bones, left clival plexus, right transverse sinus, right sigmoid sinus, and superior sagittal sinus. A diffuse pseudophlebitic pattern of venous drainage indicating severe venous hypertension was also observed. The patient underwent a series of endovascular treatments over the next 10 months to achieve resolution of all arteriovenous shunting. Repeat MRI showed resolution of the diffusion restriction and marked reduction in T2 vascular flow voids. The patient's clinical status improved significantly over the course of treatment, paralleling the improvement in venous hypertension.

Treatment of 14 intracranial aneurysms with the FRED system.

BACKGROUND: Endovascular treatment of intracranial aneurysms via flow diversion has become increasingly popular over the past several years. The flow redirection endoluminal device (FRED; Microvention, Tustin, California, USA) system is a next generation closed cell paired stent flow diversion device. OBJECTIVE: Our initial clinical experience with the FRED system is described. We believe this series to be the first use of the FRED system in the western hemisphere. METHODS: 14 aneurysms were treated utilizing the FRED system in 13 patients. Post-deployment angiography and fluoro CTs were obtained in all cases. RESULTS: Immediate post-treatment angiography demonstrated reduced flow into all aneurysms although no long term angiographic data are yet available. The device proved technically easy to deploy and recapture after partial deployment if needed. No complications, technical or otherwise, were encountered. Radiographic visibility and ability to maintain its internal cylindrical shape in tortuous arteries, as demonstrated by fluoro CT, was at least as good as the pipeline embolization device. CONCLUSIONS: The FRED system was technically easy to deploy with no procedural complications occurring in this first reported series of 14 aneurysms. The ability of the FRED system to be recaptured after partial deployment and to maintain its internal shape in tortuous vessels was demonstrated well. Long term clinical and angiographic follow-up along with prospective studies are now needed to ascertain the role of the FRED in intracranial aneurysm treatment.

Gait, hip strength and functional outcomes after a Ganz periacetabular osteotomy for adolescent hip dysplasia.

BACKGROUND: The Ganz (Bernese) periacetabular osteotomy was first described for the treatment of adult patients with hip dysplasia; however, it has also been used for adolescent patients. Its effectiveness in improving patients in the short term has not been fully established and no studies, to our knowledge, have analyzed gait and functional outcome in patients with adolescent hip dysplasia. METHODS: An Institutional Review Board-approved prospective study of a consecutive series of patients undergoing a Ganz (Bernese) periacetabular osteotomy for adolescent hip dysplasia was carried out. Standard radiographic parameters were analyzed. Harris hip scores, gait analysis, hip abductor, and flexion strength testing preoperatively and at 6 months and 1 year postoperatively were performed. Statistical analysis compared the 6-month and 1-year data to the preoperative values and a second analysis was performed comparing the patients with hip dysplasia to normative data of similarly aged patients. RESULTS: Twenty-one patients (24 hips) underwent a Ganz periacetabular osteotomy at an average age of 16.1 years for a primary diagnosis of hip dysplasia and pain. There was a significant improvement in all radiographic parameters from preoperation to 1 year in lateral center edge angle (5.5 to 33.0 degrees) (P<0.05), acetabular index of the weight-bearing zone (29.0 to 10.5 degrees) (P<0.05), ventral center edge angle (-1.1 to 32.5 degrees) (P<0.05), and medialization of the joint center relative to the contralateral side (1.12 to 1.05) (P<0.05). Isokinetic abductor strength decreased initially from 62 Nm/kg preoperatively to 58 Nm/kg at 6 months but was improved to 64 Nm/kg at 1 year. Flexion strength decreased from 92 Nm/kg preoperatively to 58 Nm/kg at 6 months but improved to 69 Nm/kg at 1 year. Abductor impulse decreased from 0.26 Nm/kg-s preoperatively to 0.23 Nm/kg-s at 6 months but improved to 0.29 Nm/kg-s at 1 year. Flexion pull-off power decreased from 1.35 Watts/kg to 1.27 Watts/kg and then improved to 1.29 Watts/kg. The Harris hip scores improved from 64.6 at the preoperative evaluation to 74.5 at the 1-year evaluation (Max 89). CONCLUSIONS: The Bernese periacetabular osteotomy is effective in significantly improving radiographic parameters for adolescent hip dysplasia with improvement in functional outcome. Because the osteotomy allows for medialization of the hip joint center and limited abductor muscle dissection the abductor strength improved at follow-up, however, the hip flexion pull-off was decreased. Strategies to improve hip flexion power preoperatively and postoperatively in the future are necessary. LEVEL OF EVIDENCE: Level IV.

Prone thoracoscopic release does not adversely affect pulmonary function when added to a posterior spinal fusion for severe spine deformity.

STUDY DESIGN: Prospective clinical study. OBJECTIVE: To analyze the effect of adding a thoracoscopic release and fusion performed in the prone position with double lung ventilation to a posterior spinal fusion and instrumentation (PSFI) for severe idiopathic scoliosis. SUMMARY OF BACKGROUND DATA: A prone thoracoscopic anterior release (TAR) offers the advantages of a minimally invasive approach, without requiring repositioning for the PSFI, and has significantly less acute pulmonary complications since single lung ventilation is avoided. It is unclear whether prone thoracoscopy adversely affects pulmonary function tests (PFT) when added to a PSFI for severe deformity. METHODS: A prospective consecutive series of patients from a single institution undergoing spinal deformity surgery were reviewed. Those patients who underwent prone TAR followed by PSFI were compared to patients who had PSFI alone. In addition, those patients who had a thoracoplasty and PSF (PSFI-T) were compared to those who had a TAR and PSFI with T. (PFTs were measured before surgery and 1, 3, 6 weeks, 3 and 6 months, and 1 year after surgery. Forced vital capacity (FVC) and FE-1 parameters were compared to baseline levels for each patient. RESULTS.: There were 13 patients in the TAR + PSFI groups and 83 in the PSFI groups. The patients in the TAR + PSFI group had larger thoracic curves (83.2 degrees vs. 59.7 degrees ), greater correction (59.4% vs. 50.1%) (P = 0.07), and greater increase in thoracic height (16.4% vs. 6.8%) following surgery. (P < 0.05) PFTs declined more rapidly for the TAR + PSFI patients in the first 3 weeks, however, improved rapidly until 1 year when they were significantly better than the PSFI group for predicted FVC % (29.7% vs. 7.5% above baseline) and forced expiratory volume (FEV) 1% (28.5% and 8.9% above baseline). (P < 0.05) When a thoracoplasty was added to the procedure, the differences in PFTs between those who had a TAR and those who did not was not significant. The TAR + PSFI-T group had FVC % predicted of 5.3% above baseline compared to 4.3% above baseline for the PSFI-T group. The percent predicted FEV 1% was 10.4% above baseline for the TAR + PSFI-T group compared to 4.5% for the PSF-T group (P > 0.05). CONCLUSION: When performing a prone thoracoscopic release for severe thoracic deformity, excellent coronal plane correction is achieved. There does not appear to be any detrimental effect on pulmonary function when a prone thoracoscopic release using double lung ventilation is added to a PSFI. This technique can be efficacious in achieving excellent deformity correction without adversely affecting pulmonary function and is recommended when treating severe spinal deformity. Adding a thoracoplasty provided a negative effect on pulmonary function and limited the benefits of performing a thoracoscopic release to the PSFI patients.