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Martin Sánchez-Aguilar, J. Humberto Tapia-Pérez, José Juan Sánchez-Rodríguez, Juan Manuel Viñas-Ríos, Patricia Martínez-Pérez, Esperanza de la Cruz-Mendoza, Martin Sánchez-Reyna, Jaime Gerardo Torres-Corzo, and Antonio Gordillo-Moscoso

Object

The favorable effect of statin treatment after traumatic brain injury (TBI) has been shown in animal studies and is probably true in humans as well. The objective of this study was to determine whether acute statin treatment following TBI could reduce inflammatory cytokines and improve functional outcomes in humans.

Methods

The authors performed a double-blind randomized clinical trial in patients with moderate to severe TBI. Exclusion criteria were as follows: prior severe disability; use of modifiers of statin metabolism; multisystem trauma; prior use of mannitol, barbiturates, corticosteroids, or calcium channel blockers; isolated brainstem lesions; allergy to statins; previous hepatopathy or myopathy; previous treatment at another clinic; and pregnancy. Patients were randomly selected to receive 20 mg of rosuvastatin or placebo for 10 days. The main goal was to determine the effect of rosuvastatin on plasma levels of tumor necrosis factor–α, interleukin (IL)–1β, IL-6, and IL-10 after 72 hours of TBI. Amnesia, disorientation, and disability were assessed 3 and 6 months after TBI.

Results

Thirty-six patients were analyzed according to intention-to-treat analysis; 19 patients received rosuvastatin and 17 received placebo. The best-fit mixed model showed a significant effect of rosuvastatin on the reduction of tumor necrosis factor–α levels (p = 0.004). Rosuvastatin treatment did not appear to affect the levels of IL-1β, IL-6, and IL-10. The treatment was associated with a reduction in disability scores (p = 0.03), indicating a favorable functional outcome. Life-threatening adverse effects were not observed.

Conclusions

The authors' data suggest that statins may induce an antiinflammatory effect and may promote recovery after TBI. The role of statins in TBI therapy should be confirmed in larger clinical trials. Clinical trial registration no.: NCT00990028.

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Juan J. Martin, Ajay Niranjan, Douglas Kondziolka, John C. Flickinger, Karl A. Lozanne, and L. Dade Lunsford

Object

Chordomas and chondrosarcomas of the skull base are aggressive and locally destructive tumors with a high tendency for local progression despite treatment. The authors evaluated the effect of stereotactic radiosurgery (SRS) on local tumor control and survival.

Methods

Twenty-eight patients with histologically confirmed chordomas (18) or chondrosarcomas (10) underwent Gamma Knife SRS either as primary or adjuvant treatment. Their ages ranged from 17 to 72 years (median 44 years). The most common presenting symptom was diplopia (26 patients, 93%). In two patients, SRS was the sole treatment. Twenty-six patients underwent between one and five additional surgical procedures. Two underwent an initial trans-sphenoidal biopsy. The average tumor volume was 9.8 cm3. The median dose to the tumor margin was 16 Gy.

Results

No patient was lost to follow-up. Transient symptomatic adverse radiation effects developed in only one patient. The actuarial local tumor control for chondrosarcomas at 5 years was 80 ± 10.1%. For chordomas both the actuarial tumor control and survival was 62.9 ± 10.4%.

Conclusions

Stereotactic radiosurgery is an important option for skull base chordomas and chondrosarcomas either as primary or adjunctive treatment. Multimodal management appears crucial to improve tumor control in most patients.

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Thomas Flannery, Hideyuki Kano, Juan J. Martin, Ajay Niranjan, John C. Flickinger, L. Dade Lunsford, and Douglas Kondziolka

Object

The aim in this study was to determine the outcomes of boost stereotactic radiosurgery, specifically Gamma Knife surgery (GKS), for recurrent primitive neuroectodermal tumors (PNETs) in children in whom initial multimodality management had failed.

Methods

The authors performed a retrospective analysis of 7 patients who underwent a total of 15 GKS procedures for locally recurrent or metastatic PNETs. Nine procedures were directed at the primary site, whereas 6 were directed at distant brain sites. All patients received multimodality therapy, including resection, fractionated radiotherapy, and chemotherapy. The mean interval from diagnosis to first stereotactic radiosurgery was 25.8 months (range 11–35 months). The mean tumor volume was 3.9 cm3 (range 1.1–13.1 cm3), and an average marginal dose of 14.5 Gy (range 9–20 Gy) was administered.

Results

Following salvage GKS, 2 patients had early disease progression (median survival of 5 months after GKS). Five patients had late disease progression (complete response in 3, partial response in 1, and stable disease in 1) and a median survival of 30 months after GKS. Four of the 5 patients who had late progression underwent repeat GKS for marginal recurrence. No adverse radiation effects were observed in these 7 patients.

Conclusions

The GKS modality was a well-tolerated and useful boost strategy in pediatric patients with PNET and a poor prognosis in whom initial multimodality management had failed. However, local or distant disease progression or diffuse leptomeningeal spread ultimately proved fatal to these patients.

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Douglas Kondziolka, Ricky Madhok, L. Dade Lunsford, David Mathieu, Juan J. Martin, Ajay Niranjan, and John C. Flickinger

Object

Meningiomas of the cerebral convexity are often surgically curable because both the mass and involved dura mater can be removed. Stereotactic radiosurgery has become an important primary or adjuvant treatment for patients with intracranial meningiomas. The authors evaluated clinical and imaging outcomes in patients with convexity meningiomas after radiosurgery.

Methods

The patient cohort consisted of 125 patients with convexity meningiomas managed using radiosurgery at some point during an 18-year period. The patient series included 76 women, 55 patients who had undergone prior resection, and 6 patients with neurofibromatosis Type 2. Tumors were located in frontal (80 patients), parietal (24 patients), temporal (12 patients), and occipital (9 patients) areas. The WHO tumor grades in patients with prior resections were Grade I in 34 patients, Grade II in 15 patients, and Grade III in 6 patients. Seventy patients underwent primary radiosurgery and therefore had no prior histological tumor diagnosis. The mean tumor volume was 7.6 ml. Radiosurgery was performed using the Leksell Gamma Knife with a mean tumor margin dose of 14.2 Gy.

Results

Serial imaging was evaluated in 115 patients (92%). After primary radiosurgery, the tumor control rate was 92%. After adjuvant radiosurgery, the control rate was 97% for Grade I tumors. The actuarial tumor control rates at 3 and 5 years for the entire series were 86.1 ± 3.8% and 71.6 ± 8.6%, respectively. For patients with benign tumors (Grade I) and those without prior surgery, the actuarial tumor control rate was 95.3 ± 2.3% and 85.8 ± 9.3%, respectively. Delayed resection after radiosurgery was performed in 9 patients (7%) at an average of 35 months. No patient developed a subsequent radiation-induced tumor. The overall morbidity rate was 9.6%. Symptomatic peritumoral imaging changes compatible with edema or adverse radiation effects developed in 5%, at a mean of 8 months.

Conclusions

Stereotactic radiosurgery provides satisfactory control rates either after resection or as an alternate to resection, particularly for histologically benign meningiomas. Its role is most valuable for patients whose tumors affect critical neurological regions and who are poor candidates for resection. Both temporary and permanent morbidity are related to brain location and tumor volume.

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Felicitas J. Detmer, Sara Hadad, Bong Jae Chung, Fernando Mut, Martin Slawski, Norman Juchler, Vartan Kurtcuoglu, Sven Hirsch, Philippe Bijlenga, Yuya Uchiyama, Soichiro Fujimura, Makoto Yamamoto, Yuichi Murayama, Hiroyuki Takao, Timo Koivisto, Juhana Frösen, and Juan R. Cebral

OBJECTIVE

Incidental aneurysms pose a challenge for physicians, who need to weigh the rupture risk against the risks associated with treatment and its complications. A statistical model could potentially support such treatment decisions. A recently developed aneurysm rupture probability model performed well in the US data used for model training and in data from two European cohorts for external validation. Because Japanese and Finnish patients are known to have a higher aneurysm rupture risk, the authors’ goals in the present study were to evaluate this model using data from Japanese and Finnish patients and to compare it with new models trained with Finnish and Japanese data.

METHODS

Patient and image data on 2129 aneurysms in 1472 patients were used. Of these aneurysm cases, 1631 had been collected mainly from US hospitals, 249 from European (other than Finnish) hospitals, 147 from Japanese hospitals, and 102 from Finnish hospitals. Computational fluid dynamics simulations and shape analyses were conducted to quantitatively characterize each aneurysm’s shape and hemodynamics. Next, the previously developed model’s discrimination was evaluated using the Finnish and Japanese data in terms of the area under the receiver operating characteristic curve (AUC). Models with and without interaction terms between patient population and aneurysm characteristics were trained and evaluated including data from all four cohorts obtained by repeatedly randomly splitting the data into training and test data.

RESULTS

The US model’s AUC was reduced to 0.70 and 0.72, respectively, in the Finnish and Japanese data compared to 0.82 and 0.86 in the European and US data. When training the model with Japanese and Finnish data, the average AUC increased only slightly for the Finnish sample (to 0.76 ± 0.16) and Finnish and Japanese cases combined (from 0.74 to 0.75 ± 0.14) and decreased for the Japanese data (to 0.66 ± 0.33). In models including interaction terms, the AUC in the Finnish and Japanese data combined increased significantly to 0.83 ± 0.10.

CONCLUSIONS

Developing an aneurysm rupture prediction model that applies to Japanese and Finnish aneurysms requires including data from these two cohorts for model training, as well as interaction terms between patient population and the other variables in the model. When including this information, the performance of such a model with Japanese and Finnish data is close to its performance with US or European data. These results suggest that population-specific differences determine how hemodynamics and shape associate with rupture risk in intracranial aneurysms.

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Lennart Riemann, Daphne C. Voormolen, Katrin Rauen, Klaus Zweckberger, Andreas Unterberg, Alexander Younsi, and the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Investigators and Participants

OBJECTIVE

The aim of this paper was to evaluate the prevalence of postconcussive symptoms and their relation to health-related quality of life (HRQOL) in pediatric and adolescent patients with mild traumatic brain injury (mTBI) who received head CT imaging during initial assessment.

METHODS

Patients aged between 5 and 21 years with mTBI (Glasgow Coma Scale scores 13–15) and available Rivermead Post Concussion Questionnaire (RPQ) at 6 months of follow-up in the multicenter, prospectively collected CENTER-TBI (Collaborative European NeuroTrauma Effectiveness Research in TBI) study were included. The prevalence of postconcussive symptoms was assessed, and the occurrence of postconcussive syndrome (PSC) based on the ICD-10 criteria, was analyzed. HRQOL was compared in patients with and without PCS using the Quality of Life after Brain Injury (QOLIBRI) questionnaire.

RESULTS

A total of 196 adolescent or pediatric mTBI patients requiring head CT imaging were included. High-energy trauma was prevalent in more than half of cases (54%), abnormalities on head CT scans were detected in 41%, and admission to the regular ward or intensive care unit was necessary in 78%. Six months postinjury, 36% of included patients had experienced at least one moderate or severe symptom on the RPQ. PCS was present in 13% of adolescents and children when considering symptoms of at least moderate severity, and those patients had significantly lower QOLIBRI total scores, indicating lower HRQOL, compared with young patients without PCS (57 vs 83 points, p < 0.001).

CONCLUSIONS

Adolescent and pediatric mTBI patients requiring head CT imaging show signs of increased trauma severity. Postconcussive symptoms are present in up to one-third of those patients, and PCS can be diagnosed in 13% 6 months after injury. Moreover, PCS is significantly associated with decreased HRQOL.