Citations

Wegener’s granulomatosis (WG) is a multisystemic necrotising granulomatous vasculitis of small and medium sized vessels, that primarily involves the upper and lower respiratory tracts, lung tissues and kidneys. Serum antineutrophil cytoplasmic antibodies (ANCA) are a sensitive and specific marker of WG. Whereas the peripheral nervous system is often involved in WG, central nervous system manifestations are reported only in 2–8%, and are rarely present at onset. We report on a patient with atypical neurological presentation of ANCA negative WG in whom the diagnosis was made only after a meningeal biopsy.

Purpose Epidermal growth factor receptor (EGFR) amplification in glioblastoma multiforme (GBM) is a common occurrence and is associated with treatment resistance. Erlotinib, a selective EGFR inhibitor, was combined with temozolomide (TMZ) and radiotherapy (RT) in a phase I/II trial. Patients and Methods Adults not taking enzyme-inducing anticonvulsants after resection or biopsy of GBM were treated with erlotinib (150 mg daily) until progression. Erlotinib was delivered alone for 1 week, then concurrently with TMZ (75 mg mg/m2 daily) and RT (60 Gy), and finally, concurrently with up to six cycles of adjuvant TMZ (200 mg/m2 daily for 5 days every 28 days). The primary end point was survival at 1 year. Results Ninety-seven eligible patients were accrued with a median follow-up time of 22.2 months. By definition, the primary end point was successfully met with a median survival time of 15.3 months. However, there was no sign of benefit in overall survival when comparing N0177 with the RT/TMZ arm of the European Organisation for Research and Treatment of Cancer/National Cancer Institute of Canada trial 26981/22981 (recursive partitioning analysis [RPA] class III, 19 v 21 months; RPA class IV, 16 v 16 months; RPA class V, 8 v 10 months, respectively). Presence of diarrhea, rash, and EGFRvIII, p53, phosphatase and tensin homolog (PTEN), combination EGFR and PTEN, and EGFR amplification status were not predictive (P > .05) of survival. Conclusion Although the primary end point was successfully met using nitrosourea-based (pre-TMZ) chemotherapy era historic controls, there was no sign of benefit compared with TMZ era controls. Analyses of molecular subsets did not reveal cohorts of patients sensitive to erlotinib. TMZ chemotherapy combined with RT resulted in improved outcomes compared with historical controls who received nitrosourea-based chemotherapies.

Object Cerebral cortex electrophysiology is poorly sampled using standard, low spatial resolution clinical intracranial electrodes. Adding microelectrode arrays to the standard clinical macroelectrode arrays increases the spatial resolution and may ultimately improve the clinical utility of intracranial electroencephalography (iEEG). However, the safety of hybrid electrode systems containing standard clinical macroelectrode and microelectrode arrays is not yet known. The authors report on their preliminary experience in 24 patients who underwent implantation of hybrid electrodes. Methods In this study, 24 consecutive patients underwent long-term iEEG monitoring with implanted hybrid depth and subdural grid and strip electrodes; both clinical macroelectrodes and research microelectrodes were used. The patients included 18 women and 6 men with an average age of 35 ± 12 years (range 21–65). The mean hospital stay was 11 ± 4 days (range 5–20), with mean duration of implantation 7.0 ± 3.2 days (range 3–15). Data from the 198 consecutive craniotomies for standard clinical subdural grid insertion (prior to surgery in the 24 patients described here) were used for comparison to investigate the relative risk of complications. Results Focal seizure identification and subsequent resection was performed in 20 patients. One patient underwent a subsequent operation after neurological deterioration secondary to cerebral swelling and a 5-mm subdural hematoma. There were no infections. The overall complication rate was 4.2% (only 1 patient had a complication), which did not significantly differ from the complication rate previously reported by the authors of 6.6% when standard subdural and depth intracranial electrodes were used. There were no deaths or permanent neurological deficits related to electrode implantation. Conclusions The authors demonstrate the use of hybrid subdural strip and grid electrodes containing high-density microwire arrays and standard clinical macroelectrodes. Hybrid electrodes provide high spatial resolution electrophysiology of the neocortex that is impossible with standard clinical iEEG. In this initial study in 24 patients, the complication rate is acceptable, and there does not appear to be increased risk associated with the use of hybrid electrodes compared with standard subdural and depth iEEG electrodes. More research is required to show whether hybrid electrode recordings will improve localization of epileptic foci and tracking the generation of neocortical seizures.

Purpose Primary CNS lymphoma (PCNSL) is an aggressive lymphoma but clinically validated biologic markers that can predict natural history to tailor treatment according to risk are lacking. Several genetic changes including BCL6 rearrangements and deletion of 6q22, containing the putative tumor suppressor gene PTPRK, are potential risk predictors. Herein we determined the prevalence and survival impact of del(6)(q22) and BCL6, immunoglobulin heavy chain (IGH), and MYC gene rearrangements in a large PCNSL cohort treated in a single center. Patients and Methods Interphase fluorescence in situ hybridization was performed using two-color probes for BCL6, MYC, IGH-BCL6, and del(6)(q22) on thin sections of 75 paraffin-embedded samples from 75 HIV-negative, immunocompetent patients newly diagnosed with PCNSL. Survival data were analyzed using Kaplan-Meier survival curves, log-rank tests, and proportional hazards regression adjusting for age, deep structure involvement, and high-dose methotrexate (HDMTX) treatment. Results The prevalence of del(6)(q22) and BCL6, IGH, and MYC translocations was 45%,17%, 13%, and 3%, respectively. The presence of del(6)(q22) and/or a BCL6 translocation was associated with inferior overall survival (OS; P = .0097). The presence of either del(6)(q22) alone or a BCL6 translocation alone was also associated with inferior OS (P = .0087). Univariable results held after adjusting for age, deep structure involvement, and HDMTX. Conclusion Del (6)(q22) and BCL6 rearrangements are common in PCNSL and predict for decreased OS independent of deep structure involvement and HDMTX. Unlike systemic diffuse large B-cell lymphoma, del(6)(q22) is common and IGH translocations are infrequent and usually involve BCL6 rather than BCL2, suggesting a distinct pathogenesis.

Abstract Purpose: Hyperactivation of the phosphatidylinositol 3-kinase/Akt signaling through disruption of PTEN function is common in glioblastoma multiforme, and these genetic changes are predicted to enhance sensitivity to mammalian target of rapamycin (mTOR) inhibitors such as RAD001 (everolimus). Experimental Design: To test whether PTEN loss could be used as a predictive marker for mTOR inhibitor sensitivity, the response of 17 serially transplantable glioblastoma multiforme xenografts was evaluated in an orthotopic therapy evaluation model. Of these 17 xenograft lines, 7 have either genomic deletion or mutation of PTEN. Results: Consistent with activation of Akt signaling, there was a good correlation between loss of PTEN function and elevated levels of Akt phosphorylation. However, of the 7 lines with disrupted PTEN function, only 1 tumor line (GBM10) was significantly sensitive to RAD001 therapy (25% prolongation in median survival), whereas 1 of 10 xenograft lines with wild-type PTEN was significantly sensitive to RAD001 (GS22; 34% prolongation in survival). Relative to placebo, 5 days of RAD001 treatment was associated with a marked 66% reduction in the MIB1 proliferation index in the sensitive GBM10 line (deleted PTEN) compared with a 25% and 7% reduction in MIB1 labeling index in the insensitive GBM14 (mutant PTEN) and GBM15 (wild-type PTEN) lines, respectively. Consistent with a cytostatic antitumor effect, bioluminescent imaging of luciferase-transduced intracranial GBM10 xenografts showed slowed tumor growth without significant tumor regression during RAD001 therapy. Conclusion: These data suggest that loss of PTEN function is insufficient to adequately predict responsiveness to mTOR inhibitors in glioblastoma multiforme.

✓Bovine tissues are now routinely used for dural closure in cranial and spinal surgery. The authors report the case of an 18-year-old woman with a history of myelomeningocele who had symptoms of tethered cord syndrome and presented to a regional hospital. At that hospital she underwent a cord untethering procedure. The spinal dura was closed with Durepair, a dural substitute derived from fetal bovine skin. Her postoperative course was complicated by a cerebrospinal fluid leak that was surgically repaired. Following this, she developed erythroderma, intermittent fevers, eosinophilia, and marked elevation in serum immunoglobulin E. She was then transferred to the authors' institution. A skin antigen test to beef was administered, which revealed a positive reaction. A radioallergosorbent test to beef also yielded positive results. She was taken to the operating room for removal of the bovine graft due to concern for an allergic reaction to the graft. The graft material showed evidence of eosinophilic infiltration. Her clinical symptoms and laboratory values all improved after surgery. To the authors' knowledge this is the first reported case of an allergic reaction to bovine-based dural substitutes.

✓ Metastatic seeding or iatrogenic implantation of numerous types of primary central nervous system tumors, typically along cerebrospinal fluid pathways, is a frequently described albeit rare phenomenon and has never been reported in association with vestibular schwannoma (VS). The authors present a case of inadvertent surgical implantation of VS into the cerebellar hemisphere during resection of a recurrent VS in the cerebellopontine angle and internal auditory canal. A 42-year-old man presented with a 2.5-cm right VS that was removed without complication via a retrosigmoid approach. Routine imaging performed 5 years later revealed a 1.5-cm recurrence of the VS that was subsequently removed by reopening the retrosigmoid craniotomy. Five years later—10 years after initial presentation—follow-up imaging revealed a 1-cm recurrence of the VS and a separate 2.2-cm tumor in the inferior cerebellar parenchyma with surrounding edema. Both tumors were removed without complication by reopening the previous retrosigmoid craniotomy. Histological evaluation of these tumors revealed features typical of VS and similar to those of the tissue obtained from the two prior resections. Given the similarities among these tumors in pathological appearance and mitotic index, the presence of the intraparenchymal cerebellar schwannoma was probably due to intraoperative iatrogenic implantation.