Cerebrospinal fluid dissemination of high-grade gliomas following boron neutron capture therapy occurs more frequently in the small cell subtype of IDH1R132H mutation-negative glioblastoma.

We have used boron neutron capture therapy (BNCT) to treat patients in Japan with newly diagnosed or recurrent high-grade gliomas and have observed a significant increase in median survival time following BNCT. Although cerebrospinal fluid dissemination (CSFD) is not usually seen with the current standard therapy of patients with glioblastoma (GBM), here we report that subarachnoid or intraventricular CSFD was the most frequent cause of death for a cohort of our patients with high-grade gliomas who had been treated with BNCT. The study population consisted of 87 patients with supratentorial high-grade gliomas; 41 had newly diagnosed tumors and 46 had recurrent tumors. Thirty of 87 patients who were treated between January 2002 and July 2013 developed CSFD. Tumor histology before BNCT and immunohistochemical staining for two molecular markers, Ki-67 and IDH1R132H, were evaluated for 20 of the 30 patients for whom pathology slides were available. Fluorescence in situ hybridization (FISH) was performed on 3 IDH1R132H-positive and 1 control IDH1R132H-negative tumors in order to determine chromosome 1p and 19q status. Histopathologic evaluation revealed that 10 of the 20 patients' tumors were IDH1R132H-negative small cell GBMs. The remaining patients had tumors consisting of other IDH1R132H-negative GBM variants, an IDH1R132H-positive GBM and two anaplastic oligodendrogliomas. Ki-67 immunopositivity ranged from 2 to 75%. In summary, IDH1R132H-negative GBMs, especially small cell GBMs, accounted for a disproportionately large number of patients who had CSF dissemination. This suggests that these tumor types had an increased propensity to disseminate via the CSF following BNCT and that these patients are at high risk for this clinically serious event.

The Effect of l-Arginine on Dural Healing After Experimentally Induced Dural Defect in a Rat Model.

BACKGROUND: Incomplete repair of the dura mater may result in numerous complications such as cerebrospinal fluid leakage and meningitis. For this reason, accurate repair of the dura mater is essential. In this study, the effect of systemic and local supplementation of l-arginine on dural healing was evaluated. METHODS: Thirty male Wistar rats were used and divided into control, local, and systemic l-arginine groups, with 10 rats in each. In each group, a 5-mm experimental incision was made at the lumbar segment of the dura mater and cerebrospinal fluid leakage was induced. Each group was divided into 2 subgroups and at the end of the first and sixth weeks, the rats were killed and the damaged segments of the dura were separated, histologically evaluated and the dural healing indicators including cell types, granulation tissue formation, collagen deposit, and vascularization were compared between groups. RESULTS: The systematic supplementation of l-arginine showed a significant effect in dural healing compared with the control group. After the first week, granulation formation increased considerably (P < 0.031), and after 6 weeks, collagen deposition and neovascularization were significantly different compared with the control group (P < 0.030; P < 0.009). In comparison between different groups at the end of the first and sixth weeks, maximum changes in healing indicators were observed in the systemic group and the least variations were related to the control group. CONCLUSIONS: The systemic supplementation of l-arginine may accelerate dural healing by increasing the level of granulation tissue formation, collagen deposition, and vascularization.

Risk of death in patients with post-traumatic cerebrospinal fluid leakage--analysis of 1773 cases.

BACKGROUND: Post-traumatic cerebrospinal fluid (CSF) leakage is one of the most troublesome conditions associated with head trauma. CSF fistulae, meningitis/central nervous infection, or even death may accompany it. Few studies have discussed post-traumatic CSF leakage as a risk factor in mortality following head trauma. We conducted this cohort study to examine the issue. METHODS: We reviewed the records in the Taiwan Traumatic Brain Injury (TBI) Registry System between 1993 and 2008. The study group included patients with acute TBI and post-traumatic CSF leakage, and the control group included cases with TBI but without CSF leakage, selected randomly at a 5:1 ratio with respect to the study group. The demographic data, Glasgow Coma Scale, brain computerized tomography, association of skull fractures and intracranial lesions, and 1-year mortality rates between these two cohorts were reviewed meticulously and analyzed statistically. RESULTS: Of 174,236 cases, 1773 with post-traumatic CSF leakage were included in the study group, and 8865 cases in the control group. Of the total 10,638 sampled cases, 406 (3.8%) died during the 1-year follow-up period, 159 (9.0%) cases in the CSF leakages group, and 247 (2.8%) in the control group. The patients with CSF leakage had a significantly higher mortality rate within 1 year (adjusted hazard ratio = 1.44, p < 0.001) than those without. We divided the CSF leakage group into three subgroups: otorrhea (n = 568), rhinorrhea (n = 302), and tension pneumocephalus (n = 903). The mortality rates were 8.5% (48/568) in the otorrhea subgroup, 10.9% (33/302) in the rhinorrhea subgroup, and 8.6% (78/903) in the tension pneumocephalus subgroup. The cases with CSF rhinorrhea had a significantly higher mortality rate than the other two subgroups (p < 0.05). All three subgroups had significantly higher mortality rates than the control group during the 1-year follow-up period (adjusted hazard ratios = 2.29, 1.35, and 1.32 in the rhinorrhea, tension pneumocephalus, and otorrhea subgroups, respectively). CONCLUSION: Post-traumatic CSF leakages had higher mortality rates than those without CSF leakages in TBI cases, and the cases with CSF rhinorrhea had worse outcomes compared with CSF leakages with pneumocephalus or otorrhea.

Cranial injuries secondary to assault with a machete.

BACKGROUND: Assaults with a machete cause compound skull fractures which present as a neurosurgical emergency. We aimed to profile cranial injuries caused by a machete over a 10 year period in a single neurosurgical unit. MATERIALS AND METHODS: Retrospective data analysis of cranial injuries following assault with a machete, admitted to the neurosurgery ward, from January 2003 to December 2012 was performed. Medical records were analyzed for demographics, clinical presentation, CT scan findings, surgical treatment and Glasgow Outcome Scale (GOS) at discharge. Management involved wound debridement with antibiotic cover. RESULTS: Of 185 patients treated 172 (93%) were male. Mean age was 31±11.4 years. Mean GCS on admission was 13±2. Presenting features were focal neurological deficit (48%), brain matter oozing from wounds (20%), and post traumatic seizures (12%). Depressed skull fractures were found in 162 (88%) patients. Findings on CT brain scan were intra-cranial haematoma (88%), pneumocephalus (39%) and features of raised intra-cranial pressure (37%). Thirty-one patients (17%) presented with septic head wounds. One hundred and fifty seven patients (85%) were treated surgically. The median hospital stay was 8 days (range 1-145). The median GOS at discharge was 5 (range 1-5). Twelve patients died within the same admission (6.5%). CONCLUSION: Machetes cause complex cranial injuries with associated neurological deficit and should be treated as neurosurgical emergency. Timeous intervention and good surgical principles are advocated to prevent secondary infection and further neurological deterioration.