Granular cell astrocytoma: an aggressive IDH-wildtype diffuse glioma with molecular genetic features of primary glioblastoma.

Granular cell astrocytoma (GCA) is a rare adult infiltrating glioma subtype. We studied a series of 39 GCAs. Median age of presentation was 57.8 years and most cases developed in the frontal or temporal lobes. Tumors included grade II (n = 14), grade III (n = 11), and grade IV (n = 14) by WHO criteria. Granular cell morphology was diffuse in 31 (79%) cases and partial in eight (21%). Immunohistochemistry showed frequent positivity for GFAP (28 of 31), OLIG2 (16 of 16), and CD68 (27 of 30), but HAM56, CD163, and IBA-1 histiocytic markers were all negative (22 of 22). IDH1(R132H) was negative in all the cases tested (16 of 16), while ATRX expression was retained (12 of 12). Cytogenetics demonstrated monosomy 10 (6 of 6) cases, +7 in 4 (of 6), -13q in 4 of 6, and -14 in 4 of 6. Next-generation sequencing demonstrated mutations in PTEN/PIK3 genes in 6/13 (46%), NF1 in 3 of 10 (30%), TP53 in 3 of 13 (23%), PALB2 in 3 of 10 (30%), STAG2 in 3 of 10 (30%), EGFR mutation/amplification in 3 of 13 (23%), and AR in 2 of 10 (20%). CDKN2A/B deletion was identified in 5 of 13 (30%) cases (homozygous deletion in 4). The TERT C228T mutation was identified in 9 of 13 (69%). No mutations were encountered in IDH1, IDH2, CIC, FUBP1, H3F3A, BRAF or ATRX genes. The mean overall survival was 11.3 months. Patients >60 years old at diagnosis had a worse survival than patients <60 years (P = 0.001). There were no statistically significant differences in survival by WHO grade, extent of granular cell change, sex or MIB-1 (P > 0.05). GCA is a variant of IDH-wildtype diffuse glioma with aggressive behavior irrespective of grade and extent of granular cell morphology, and with molecular genetic features corresponding to primary glioblastoma.

Methylprednisolone Administration Following Spinal Cord Injury Reduces Aquaporin 4 Expression and Exacerbates Edema.

Spinal cord injury (SCI) is an incapacitating condition that affects motor, sensory, and autonomic functions. Since 1990, the only treatment administered in the acute phase of SCI has been methylprednisolone (MP), a synthetic corticosteroid that has anti-inflammatory effects; however, its efficacy remains controversial. Although MP has been thought to help in the resolution of edema, there are no scientific grounds to support this assertion. Aquaporin 4 (AQP4), the most abundant component of water channels in the CNS, participates in the formation and elimination of edema, but it is not clear whether the modulation of AQP4 expression by MP plays any role in the physiopathology of SCI. We studied the functional expression of AQP4 modulated by MP following SCI in an experimental model in rats along with the associated changes in the permeability of the blood-spinal cord barrier. We analyzed these effects in male and female rats and found that SCI increased AQP4 expression in the spinal cord white matter and that MP diminished such increase to baseline levels. Moreover, MP increased the extravasation of plasma components after SCI and enhanced tissue swelling and edema. Our results lend scientific support to the increasing motion to avoid MP treatment after SCI.

Multicentric Spinal Cord Glioblastoma.

A 40-year-old man was referred to our center with a 4-month history of progressive quadriparesis. Previous brain imaging revealed no abnormality. Magnetic resonance imaging (MRI) with contrast of the cervicothoracic spine revealed 2 heterogeneously enhancing lesions at the level of C3-C5 and T2-T4 (A); T1- and T2-weighted MRI showed hypointense and hyperintense lesions, respectively, which is characteristic of spinal cord astrocytoma (B and C). Intraoperative biopsies supported the diagnosis of glioblastoma (hypercellularity, vascular proliferation, and tumor cell palisading around necrosis) (D). Though resection was attempted, surgery was aborted due to hemodynamic instability and signal changes in neuromonitoring. The patient stabilized in the intensive care unit and experienced slight improvement in upper extremity strength. After discharge without further complications, the patient was expected to return for further adjuvant therapy/surgical planning but unfortunately passed away 1.5 months after his operation, most likely to rapid disease progression.

The butterfly effect on glioblastoma: is volumetric extent of resection more effective than biopsy for these tumors?

A subset of patients with glioblastoma (GBM) have butterfly GBM (bGBM) that involve both cerebral hemispheres by crossing the corpus callosum. The prognoses, as well as the effectiveness of surgery and adjuvant therapy, are unclear because studies are few and limited. The goals of this study were to: (1) determine if bGBM have worse outcomes than patients with non-bGBM, (2) determine if surgery is more effective than biopsy, and (3) identify factors independently associated with improved outcomes for these patients. Adult patients who underwent surgery for a newly diagnosed primary GBM at an academic tertiary-care institution between 2007 and 2012 were retrospectively reviewed and tumors were volumetrically measured. Of the 336 patients with newly diagnosed GBM who were operated on, 48 (14 %) presented with bGBM, where 29 (60 %) and 19 (40 %) underwent surgical resection and biopsy, respectively. In multivariate analysis, a bGBM was independently associated with poorer survival [HR (95 % CI) 1.848 (1.250-2.685), p < 0.003]. In matched-pair analysis, patients who underwent surgical resection had improved median survival than biopsy patients (7.0 vs. 3.5 months, p = 0.03). In multivariate analysis, increasing percent resection [HR (95 % CI) 0.987 (0.977-0.997), p = 0.01], radiation [HR (95 % CI) 0.431 (0.225-0.812), p = 0.009], and temozolomide [HR (95 % CI) 0.413 (0.212-0. 784), p = 0.007] were each independently associated with prolonged survival among patients with bGBM. This present study shows that while patients with bGBM have poorer prognoses compared to non-bGBM, these patients can also benefit from aggressive treatments including debulking surgery, maximal safe surgical resection, temozolomide chemotherapy, and radiation therapy.

When gross total resection of a glioblastoma is possible, how much resection should be achieved?

OBJECTIVE: The efficacy of extensive resection on prolonging survival for patients with glioblastoma (GBM) is controversial because prior studies have included tumors with dissimilar resection capabilities. The true isolated effect of increasing resection on survival for GBM therefore remains unclear. METHODS: Adult patients who underwent surgery of an intracranial newly diagnosed GBM at an academic tertiary-care institution from 2007 to 2011 were reviewed. Preoperative images were reviewed by 3 neurosurgeons independently. Tumors considered amenable to gross total resection based on preoperative imaging by all neurosurgeons were included. Multivariate proportional hazards regression analysis was used to identify if an association existed between residual volume (RV) and extent of resection (EOR) with survival. RESULTS: Of the 292 patients with newly diagnosed GBM, 84 (29%) were amenable to gross total resection. The median (interquartile range) pre and postoperative tumor volumes were 27 (13.8-54.4) and 0.9 (0-2.7) cm(3), respectively. The mean percent resection was 91.7% ± 1.3%. In multivariate analysis, after controlling for age, functional status, and adjuvant therapies, RV (hazards ratio [HR] [95% confidence interval (CI)] = 1.114 [1.033-1.193], P = 0.006) and EOR (HR [95% CI] = 0.959 [0.934-0.985], P = 0.003) were each independently associated with survival. The RV and EOR with the greatest reduction in the risk of death was <2 cm(3) and >95%, respectively. Likewise, RV (HR [95% CI] = 1.085 [1.010-1.178], P = 0.01) and EOR (HR [95% CI] = 0.962 [0.930-0.998], P = 0.04) each remained independently associated with recurrence. CONCLUSION: This is the first study to evaluate RV and EOR in a more uniform population of patients with tumors of similar surgical capabilities. This study shows that achieving a decreased RV and/or an increased EOR is independently associated with survival and recurrence in those patients with tumors with similar resection capacities.

Operative technique for en bloc resection of upper cervical chordomas: extended transoral transmandibular approach and multilevel reconstruction.

Anterior exposure for cervical chordomas remains challenging because of the anatomical complexities and the restoration of the dimensional balance of the atlanto-axial region. In this report, we describe and analyze the transmandibular transoral approach and multilevel spinal reconstruction for upper cervical chordomas. We report two cases of cervical chordomas (C2 and C2-C4) that were treated by marginal en bloc resection with a transmandibular approach and anterior-posterior multilevel spinal reconstruction/fixation. Both patients showed clinical improvement. Postoperative imaging was negative for any residual tumor and revealed adequate reconstruction and stabilization. Marginal resection requires more extensive exposure to allow the surgeon access to the entire pathology, as an inadequate tumor margin is the main factor that negatively affects the prognosis. Anterior and posterior reconstruction provides a rigid reconstruction that protects the medulla and decreases axial pain by properly stabilizing the cervical spine.