Safety and Efficacy of the Off-Label Use of Pipeline Embolization Device Based on the 2018 Food and Drug Administration-Approved Indications for Intracranial Aneurysms: A Single-Center Retrospective Cohort Study.

BACKGROUND: The pipeline embolization device (PED; ev3/Covidien) has proven safe and effective for treating selected intracranial aneurysms. This device's versatility and popularity have driven increased interest in expanding the latest 2018 Food and Drug Administration-approved indications. OBJECTIVE: To compare "off-label" and "on-label" PED treatment. METHODS: Retrospective analysis of aneurysms treated with PED at a single center from 2013 to 2019. Comparisons were made based on the 2018 Food and Drug Administration-approved indications. RESULTS: A total of 492 treated aneurysms were included (65.2% on-label and 34.8% off-label). Aneurysm complete and near-complete occlusion rate was nonsignificantly lower in the off-label group (80.9% vs 85.7%; P = .19). Off-label treatment had higher rate of poor functional outcomes (modified Rankin Scale [mRS] >2: 10.3% vs 3.5%; P = .002). Although pretreatment mRS was already higher in the off-label group (5.3% vs 0.3%; P < .001) and there were no differences in mRS worsening during follow-up (5.5% vs 2.9%; P = .15). We also found a trend to a higher rate of intracranial hemorrhagic complications in the off-label group (4.7% vs 1.6%; P = .05), but there were no differences in hemorrhages requiring surgical intervention (1.8% vs 1.3%; P = .65). There were no differences in retreatment, thromboembolic complications, and mortality rates. CONCLUSION: Off-label PED treatment may be considered for select aneurysms, which are challenging to treat with other techniques. These cases have similar complete and near-complete occlusion rates compared with on-label cases. There are, however, higher risks of poor functional outcomes despite similar rates of thromboembolic and hemorrhagic complications. This is partly explained by the significantly higher pretreatment mRS score in the off-label group.

Factors Affecting the Diagnostic Yield of Frame-Based Stereotactic Intracranial Biopsies.

OBJECTIVE: Frame-based stereotactic biopsy (FSB) remains the "gold standard" for obtaining diagnostic samples of intracranial lesions to guide therapy. Nevertheless, diagnostic yield is highly variable. This study aims to provide an analysis of diagnostic yield, surgical complications, and factors associated with obtaining nondiagnostic samples in a contemporary FSB series. METHODS: A retrospective cohort study was conducted of all adult patients with imaging-documented lesions undergoing FSB at our institution between 2013 and 2018. Diagnostic accuracy, lesion characteristics associated with nondiagnostic biopsy, and surgical complications were evaluated. A biopsy was considered nondiagnostic if all frozen samples and the final pathology yielded normal brain tissue or nonspecific reactive tissue unless the "reactive" pathology was consistent with radiation injury from prior therapy. RESULTS: Our search identified 198 FSB patients. Mean (standard deviation) age was 62 ± 17 years, and 44.2% were female. Median procedure time was 32 minutes. A definitive histologic diagnosis was established in 187 cases (94.4% diagnostic yield). Mean lesion diameter was 31.9 ± 16.8 mm. Multivariable logistic regression revealed only lesion diameter to be significantly associated with diagnostic result (odds ratio for nondiagnostic result: 0.94 per mm diameter decrease, 95% confidence interval 0.87-0.99, P = 0.028). On univariable analysis, diagnosis of central nervous system lymphoma appeared to increase the risk of a nondiagnostic biopsy (P = 0.025), but this association disappeared when controlling for lesion size and steroid administration before biopsy. Eight patients (4.0%) developed postoperative hemorrhagic complications, 3 of whom required reoperation, and another expired. CONCLUSIONS: This study demonstrates that diagnostic yield from contemporary FSB is high and depends predominantly on lesion size.

Masson's tumor of the pineal region: case report.

Intracranial intravascular papillary endothelial hyperplasia (IPEH), also referred to as Masson's tumor, is a condition that rarely occurs in the nervous system. IPEH most frequently occurs extracranially in the skin of the face, skull, neck, and trunk and can easily be mistaken clinically, radiologically, and histologically for angiosarcoma, organizing hematoma, or other vascular malformations. IPEH accounts for roughly 2% of all vascular tumors and is extremely rare intracranially, with only 23 reported cases compared with more than 300 cases of IPEH occurring in the skin and subcutaneous tissue. To date, it has never been reported to occur in the pineal region. The authors report the case of a patient with an IPEH in the pineal region who underwent complex resection and experienced reversal of neurological symptoms.

Affective disorders influence clinical outcomes after revision lumbar surgery in elderly patients with symptomatic adjacent-segment disease, recurrent stenosis, or pseudarthrosis: clinical article.

OBJECT: Depression and persistent low-back pain (LBP) are common and disabling problems in elderly patients (> 65 years old). Affective disorders, such as depression and anxiety, are also common in elderly patients, with a prevalence ranging from 4% to 16%. Depressive symptoms are consistently associated with functional disability. To date, few studies have assessed the predictive value of baseline depression on outcomes in the setting of revision spine surgery in elderly patients. Therefore, in this study, the authors assessed the predictive value of preoperative depression on 2-year postoperative outcomes. METHODS: A total of 69 patients undergoing revision neural decompression and instrumented fusion for adjacent-segment disease (ASD, n = 28), pseudarthrosis (n = 17), or same-level recurrent stenosis (n = 24) were included in this study. Preoperative Zung Self-Rating Depression Scale (ZDS) scores were assessed for all patients. Preoperative and 2-year postoperative visual analog scale (VAS) scores for back pain (VAS-BP) and leg pain (VAS-LP) and the Oswestry Disability Index (ODI) were also assessed. The association between preoperative ZDS score and 2-year improvement in disability was assessed via multivariate regression analysis. RESULTS: Compared with preoperative status, 2-year postoperative VAS-BP was significantly improved after surgery for ASD (9 ± 2 vs. 4.01 ± 2.56, respectively; p = 0.001), as were pseudarthrosis (7.41 ± 1 vs. 5.0 ± 3.08, respectively; p = 0.02) and same-level recurrent stenosis (7 ± 2.00 vs. 5.00 ± 2.34, respectively; p = 0.003). Two-year ODI was also significantly improved after surgery for ASD (29 ± 9 vs. 23.10 ± 10.18, respectively; p = 0.001), as were pseudarthrosis (28.47 ± 5.85 vs. 24.41 ± 7.75, respectively; p = 0.001) and same-level recurrent stenosis (30.83 ± 5.28 vs. 26.29 ± 4.10, respectively; p = 0.003). Independent of other factors-age, body mass index, symptom duration, smoking, comorbidities, severity of preoperative pain, and disability-increasing preoperative ZDS score was significantly associated with lower 2-year improvement in disability (ODI) after revision surgery in elderly patients with symptomatic ASD, pseudarthrosis, or recurrent stenosis. CONCLUSIONS: The extent of preoperative depression is an independent predictor of less functional improvement following revision lumbar surgery in elderly patients with symptomatic ASD, pseudarthrosis, or recurrent stenosis. Timely diagnosis and treatment of depression and somatic anxiety in this cohort of patients may contribute to improvement in postoperative functional status.

Caspase-11 controls interleukin-1ß release through degradation of TRPC1.

Caspase-11 is a highly inducible caspase that controls both inflammatory responses and cell death. Caspase-11 controls interleukin 1ß (IL-1ß) secretion by potentiating caspase-1 activation and induces caspase-1-independent pyroptosis downstream of noncanonical NLRP3 inflammasome activators such as lipopolysaccharide (LPS) and Gram-negative bacteria. However, we still know very little about the downstream mechanism of caspase-11 in regulating inflammation because the known substrates of caspase-11 are only other caspases. Here, we identify the cationic channel subunit transient receptor potential channel 1 (TRPC1) as a substrate of caspase-11. TRPC1 deficiency increases the secretion of IL-1ß without modulating caspase-1 cleavage or cell death in cultured macrophages. Consistently, trpc1(-/-) mice show higher IL-1ß secretion in the sepsis model of intraperitoneal LPS injection. Altogether, our data suggest that caspase-11 modulates the cationic channel composition of the cell and thus regulates the unconventional secretion pathway in a manner independent of caspase-1.

Fibrin sealant augmentation with autologous pericranium for duraplasty after suboccipital decompression in Chiari 1 patients: A case series.

BACKGROUND: The Chiari 1 malformation (CM1) involves decent of the tonsils of the cerebellum through the foramen magnum. Symptomatic disease requires a posterior fossa decompression with or without an expansile duraplasty. To date, the optimal surgical treatment for CM1 has not been delineated. The extent of bony removal, size of the dural opening, necessity for expansion of the dural space, choice of materials for the duraplasty, and possible need for augmentation with dural sealant are all factors that continue to be debated amongst neurological surgeons worldwide. We herein evaluate the use of fibrin sealant augmentation in combination with locally harvested autologous pericranium for duraplasty in adult CM1 decompression. METHODS: Retrospective data collected from January 2006 to December 2011. Data were reviewed for surgical site infection or meningitis, cerebrospinal fluid leak, symptomatic pseudomeningocele, radiographic improvement of hindbrain compression, and postoperative recurrence of symptoms at a minimum of 1 year of follow-up. Outcomes were studied clinically, radiographically, as well as by using a patient-specific questionnaire. RESULTS: Twenty-two consecutive patients were included. One patient required a revision for a delayed graft dehiscence in the setting of a rare form of aseptic meningitis with cerebrospinal fluid (CSF) pleocytosis due to a nonsteroidal anti-inflammatory drug (NSAID) allergy. All remaining patients had successful decompressions with full resolution of their symptoms except for one patient who had persistent headaches. CONCLUSION: Autologous pericranium with dural sealant augmentation is an effective technique for expansile duraplasty in CM1 decompressions.

Cleavage of TRPM7 releases the kinase domain from the ion channel and regulates its participation in Fas-induced apoptosis.

Transient receptor potential melastatin-like 7 (TRPM7) is a channel protein that also contains a regulatory serine-threonine kinase domain. Here, we find that Trpm7-/- T cells are deficient in Fas-receptor-induced apoptosis and that TRPM7 channel activity participates in the apoptotic process and is regulated by caspase-dependent cleavage. This function of TRPM7 is dependent on its function as a channel, but not as a kinase. TRPM7 is cleaved by caspases at D1510, disassociating the carboxy-terminal kinase domain from the pore without disrupting the phosphotransferase activity of the released kinase but substantially increasing TRPM7 ion channel activity. Furthermore, we show that TRPM7 regulates endocytic compartmentalization of the Fas receptor after receptor stimulation, an important process for apoptotic signaling through Fas receptors. These findings raise the possibility that other members of the TRP channel superfamily are also regulated by caspase-mediated cleavage, with wide-ranging implications for cell death and differentiation.