Natural history of cavernous sinus meningiomas.

OBJECTIVEMeningiomas confined to the cavernous sinus (MCSs) are benign tumors. Due to the high risk of severe complications, the intracavernous surgical procedure was abandoned in favor of radiotherapy. However, the choice of treatment remains complicated due to the fact that the natural history of this lesion has not yet been described.METHODSThe authors studied the natural history of this lesion using a prospective series of 53 consecutive patients suffering from MCSs. The median follow-up duration was 10.2 years (range 2-25 years), from 1990 to 2016.RESULTSPatients ranged in age from 30 to 72 years (mean 53 years). The meningiomas were diagnosed by major symptoms (mainly oculomotor palsy and neuralgia experienced in 28 patients), minor symptoms (headache, intermittent diplopia in 15 patients), or incidental findings (10 patients). Simple symptomatic treatment (short courses of corticosteroids and carbamazepine) allowed patients to become asymptomatic in 19 (67.9%) of 28 cases experiencing major symptoms, and for 12 (80%) of 15 patients with initial minor symptoms (p < 0.0001). All patients with incidental findings remained asymptomatic. Forty four (83%) of 53 MCSs did not show any significant growth and 42 (80%) of 53 patients were not symptomatic at the end of follow-up (p < 0.001). The radiographic progression-free survival rates (± SD) at 5, 10, and 20 years were 90% ± 4.2%, 82% ± 5.7%, and 70% ± 10.2%, respectively. Five patients (9.4%) with no evidence of any effect of the initial medical treatment desired additional conventional radiation therapy.CONCLUSIONSBecause of the capricious, unpredictable, and slow growth of MCSs, together with high growth variability from one patient to the next, the symptomatic medical treatment of these tumors is a highly effective method. This series shows that these lesions are naturally, clinically, and radiologically indolent.

Markers of recurrence and long-term morbidity in craniopharyngioma: a systematic analysis of 171 patients.

CONTEXT: Craniopharyngiomas are often associated with an unfavorable prognosis, but data on their long-term consequences are sparse. OBJECTIVE: The aim of the study was to identify markers of recurrence and factors associated with compromised social rehabilitation and altered quality of life in a large cohort of patients with either childhood-onset (CO) or adult-onset craniopharyngioma. METHODS: Retrospective analysis was performed for 171 patients treated for craniopharyngioma in two academic centers in France between 1972 and 2009. For each subject, data were collected concerning clinical presentation, imaging features, visual sequelae, endocrine and metabolic impact, treatment modalities (surgery, radiotherapy), recurrence-free survival rate, and social insertion, as well as answers to the WHO-QOL BREF questionnaire. RESULTS: A total of 65 CO and 106 adult-onset patients were reviewed. If CO was diagnosed before the age of 10 yr, this was associated with a higher incidence of obesity, blindness, and panhypopituitarism, and only 40.7% of subjects had adequate work or school attendance compared to 72.4% of patients with later disease onset. Initial symptoms of intracranial hypertension (SIHT), pterional surgery, and multiple surgery were associated with obesity and poorer social insertion. No determinant of quality of life was identified. In the subgroup of patients treated in the 1990s and later, the progression rate was 59.4% in patients with residual tumor on magnetic resonance imaging compared with a 19.8% recurrence rate in the group with apparently complete resection. Recurrence/progression correlates significantly with male gender, early onset (before 10 yr), and SIHT, but only SIHT at presentation remained a significant predictor with multivariate analysis. CONCLUSIONS: Craniopharyngioma continues to be associated with severe outcomes. Higher morbidity rates are found in patients with early-onset disease (before 10 yr), initial SIHT, or in whom pterional surgery was required. Markers of recurrence are difficult to identify, with SIHT being the most powerful predictor.

Conservative management of endolymphatic sac tumors in von Hippel-Lindau disease: case report.

In endolymphatic sac tumors associated with von Hippel-Lindau disease, early detection and surgery have been warranted to avoid associated neurological morbidity. However, in lately discovered tumors, hearing preserving surgery is often impossible and timing of surgical resection is difficult to define. We report two cases of tumors revealed by a sudden and profound hearing loss and managed conservatively for more than 15 years without worsening of the neurological symptoms associated with the endolymphatic sac tumor. Tumor size remained stable for the first patient and a stuttering growth pattern was observed for the second patient. Initial observation may be considered a not unreasonable management paradigm in these cases.

Natural history of supratentorial hemangioblastomas in von Hippel-Lindau disease.

BACKGROUND: Supratentorial hemangioblastomas are rare lesions, occurring either sporadically or in von Hippel-Lindau disease. OBJECTIVE: Following recent advances in our understanding of the natural history of von Hippel-Lindau-associated cerebellar and spinal hemangioblastomas, we conducted a study of the natural history of supratentorial hemangioblastomas in von Hippel-Lindau disease. METHODS: We reviewed a series of 18 supratentorial hemangioblastomas in 13 patients with von Hippel-Lindau disease. Clinical, genetic, and serial imaging data and operative records were analyzed. RESULTS: Hemangioblastomas were most commonly seen in the temporal lobe. Only 6 tumors had a cyst at diagnosis or during follow-up, and only 6 patients had associated symptoms at presentation or during follow-up. The most frequent clinical presentations were intracranial hypertension and visual loss. Of 14 tumors with documented serial imaging, 13 demonstrated tumor growth. Rates and patterns of tumor growth were unique to each patient. The mechanism of cyst formation described in other locations was also demonstrated in the supratentorial region. Patterns of peritumoral edema and rate of cyst formation seemed to be influenced by the presence of anatomic barriers. Germline VHL mutation was identified in all patients, but no specific genotype-phenotype correlation was found, although a familial predisposition is suggested. CONCLUSION: This series illustrates the wide variation in tumor locations, patterns of growth, and edema progression seen in supratentorial hemangioblastomas and adds to our knowledge of the natural history of hemangioblastomas.

Phase 1 trial of a CpG oligodeoxynucleotide for patients with recurrent glioblastoma.

Oligodeoxynucleotides containing CpG motifs (CpG ODNs) display a strong immunostimulating activity and drive the immune response toward the Th1 (T helper type 1) phenotype. These ODNs have shown promising efficacy in preclinical studies when injected locally in several cancer models. We conducted a phase 1 trial to define the safety profile of CpG-28, a phosphorothioate CpG ODN, administered intratumorally by convection-enhanced delivery in patients with recurrent glioblastoma. Cohorts of three to six patients were treated with escalating doses of CpG-28 (0.5-20 mg), and patients were observed for at least four months. Twenty-four patients entered the trial. All patients had previously been treated with radiotherapy, and most patients had received one or several types of chemotherapy. Median age was 58 years (range, 25-73) and median KPS was 80% (range, 60%-100%). Adverse effects possibly or probably related to the studied drug were moderate and consisted mainly in worsening of neurological conditions (four patients), fever above 38 degrees C that disappeared within a few days (five patients), and reversible grade 3 lymphopenia (seven patients). Only one patient experienced a dose-limiting toxicity. Preliminary evidence of activity was suggested by a minor response observed in two patients and an overall median survival of 7.2 months. In conclusion, CpG-28 was well tolerated at doses up to 20 mg per injection in patients with recurrent glioblastoma. Main side effects were limited to transient worsening of neurological condition and fever.

Survivin expression in ganglioglioma.

Gangliogliomas are unusual central nervous system (CNS) neoplasms occurring mainly in children and young adults and inducing chronic pharmacoresistant epilepsy. These are usually well differentiated neuroepithelial tumors composed of neurons in association with neoplastic glial cells. Gangliogliomas present with favorable outcome. However, some may recur and/or progress to anaplasia and be associated with a dismal prognosis. Since histopathological features do not consistently correlate with clinical outcome, reliable prognostic factors have yet to be defined in gangliogliomas. Survivin is an anti-apoptotic protein whose expression has been found to be of prognostic significance in many human cancers, including gliomas. The objective of this study was to assess survivin expression using immunohistochemistry in 15 gangliogliomas. Ten lesions were low-grade neoplasms whereas 5 were high-grade tumors. Survivin expression appeared restricted to the neoplastic glial component and was detected in 6/15 gangliogliomas. Two additional tumors expressed survivin upon relapse. Half survivin expressing lesions displayed less than 1% immunoreactive cells. Survivin expression in more than 5% neoplastic glial cells was detected only in malignant and/or recurrent gangliogliomas. Extended lifespan in survivin expressing cells might enhance aggressive behavior in these tumors through accumulation of mutations, thereby allowing progression to malignant phenotypes. Survivin expression may carry a negative prognostic value in gangliogliomas.

Hemangioblastomas of the lower spinal region: report of four cases with preoperative embolization and review of the literature.

BACKGROUND AND PURPOSE: Hemangioblastomas (HBs) are rare lesions accounting for 1-5% of all spinal cord tumors. Seventy-five percent of spinal HBs are intramedullary. Lesions of the conus medullaris and the cauda equina are uncommon, and the filum terminale location is very rare. HBs of the lower spinal region are highly vascular tumors requiring surgery that is potentially complicated by excessive bleeding. In the literature, there are few reports concerning preoperative embolization of HBs, and only few cases are reported in spinal location. Presurgical embolization of HBs located in the lower spinal region has not been described. Although lower spinal HBs are predominantly fed by the anterior spinal artery (ASA), embolization of these lesions is possible and can reduce tumor vascular supply, thus facilitating surgery. We report our experience in four rare cases of solitary HBs occurring in the lower spinal region. METHODS: Clinical charts and radiologic studies of four patients with a preoperatively embolized HB of the lower spinal region were retrospectively reviewed. The lesions were located in the conus medullaris in one case, at the level of the cauda equina in another, and in the filum terminale in two. In the conus medullaris case, the neoplasm was associated with a syrinx. In three patients, the HB was sporadic, while the patient with the HB of the cauda equina had Von Hippel-Lindau disease. Devascularization of the tumor was performed through the ASA in all cases and also through the posterior spinal artery in one by using non reabsorbable calibrated microspheres in three cases and polyvinyl alcohol particles in the other one. RESULTS: Embolization caused no permanent complications, although one patient with a cauda equina HB mildly worsened after the endovascular procedure but recovered before surgery. At surgery, the tumor was completely removed in all cases. Blood loss was reported to be less than usually observed (100, 200, 200, and 400 mL). In addition, manipulation and removal of the tumor was reported to be easy in three of four tumors. Histologic examination confirmed the diagnosis. At 1-year postsurgical follow-up, two patient recovered completely from neurologic deficits, and two showed significant recovery. No tumor recurred during a follow-up period of 1-6 years (mean, 3.5 years). CONCLUSION: Our results indicate that preoperative embolization of HBs of the lower spinal region is an useful procedure in aiding surgical resection of these highly vascular tumors. With a meticulous technique, embolization can be performed through the ASA.

The role of dominant premotor cortex in language: a study using intraoperative functional mapping in awake patients.

Although the role of the premotor cortex (PMC) was widely studied in motor function, very few data are currently available about the participation of this structure in language. We report a series of 25 right-handed patients harboring a low-grade glioma near or within the left dominant PMC, operated on under local anesthesia with intraoperative real-time sensorimotor and language mappings using electrical stimulations all along the resection. Language tasks consisted of counting and picture naming (preceded by the reading of a short sentence). Stimulations of the left PMC induced transient speech disturbances in all patients, with disruption of both counting and reading/naming during stimulation of the ventral PMC--due to elicitation of an anarthria--while generating an anomia during stimulation of the dorsal PMC. Moreover, corresponding subcortical pathways generated the same language disorders as at the cortical level when stimulated. Eloquent structures were systematically preserved, allowing the avoidance of definitive postoperative deficit. These findings suggest first that the left dominant PMC seems to play a major role in language and second that this structure could have a well-ordered functional organization, namely with the ventral PMC, which might be involved in planification of articulation, and the dorsal PMC, which might be involved in the naming network.

Usefulness of intraoperative electrical subcortical mapping during surgery for low-grade gliomas located within eloquent brain regions: functional results in a consecutive series of 103 patients.

OBJECT: Although a growing number of authors currently advocate surgery to treat low-grade gliomas, controversy still persists, especially because of the risk of inducing neurological sequelae when the tumor is located within eloquent brain areas. Many researchers performing preoperative neurofunctional imaging and intraoperative electrophysiological methods have recently reported on the usefulness of cortical functional mapping. Despite the frequent involvement of subcortical structures by these gliomas, very few investigators have specifically raised the subject of fiber tracking. The authors in this report describe the importance of mapping cortical and subcortical functional regions by using intraoperative real-time direct electrical stimulations during resection of low-grade gliomas. METHODS: Between 1996 and 2001, 103 patients harboring a corticosubcortical low-grade glioma in an eloquent area, with no or only mild deficit, had undergone surgery during which intraoperative electrical mapping of functional cortical sites and subcortical pathways was performed throughout the procedure. Both eloquent cortical areas and corresponding white fibers were systematically detected and preserved, thus defining the resection boundaries. Despite an 80% rate of immediate postoperative neurological worsening, 94% of patients recovered their preoperative status within 3 months--10% even improved--and then returned to a normal socioprofessional life. Eighty percent of resections were classified as total or subtotal based on control magnetic resonance images. CONCLUSIONS: The use of functional mapping of the white matter together with cortical mapping allowed the authors to optimize the benefit/risk ratio of surgery of low-grade glioma invading eloquent regions. Given that preoperative fiber tracking with the aid of neuroimaging is not yet validated, we used intraoperative real-time cortical and subcortical stimulations as a valuable adjunct to the other mapping methods.

Continuous growth of mean tumor diameter in a subset of grade II gliomas.

Serial magnetic resonance images of 27 patients with untreated World Health Organization grade II oligodendrogliomas or mixed gliomas were reviewed retrospectively to study the kinetics of tumor growth before anaplastic transformation. Analysis of the mean tumor diameters over time showed constant growth. Linear regression, using a mixed model, found an average slope of 4.1mm per year (95% confidence interval, 3.8-4.4mm/year). Untreated low-grade oligodendrogliomas or mixed gliomas grow continuously during their premalignant phase, and their pattern of growth can be predicted within a relatively narrow range. These findings could be of interest to optimize patients management and follow-up.