Iddo Paldor

Giant anterior clinoidal meningiomas: surgical technique and outcomes

OBJECT Surgery for giant anterior clinoidal meningiomas that invade vital neurovascular structures surrounding the anterior clinoid process is challenging. The authors present their skull base technique for the treatment of giant anterior clinoidal meningiomas, defined here as globular tumors with a maximum diameter of 5 cm or larger, centered around the anterior clinoid process, which is usually hyperostotic. METHODS Between 2000 and 2010, the authors performed 23 surgeries in 22 patients with giant anterior clinoidal meningiomas. They used a skull base approach with extradural unroofing of the optic canal, extradural clinoidectomy (Dolenc technique), transdural debulking of the tumor, early optic nerve decompression, and early identification and control of key neurovascular structures. RESULTS The mean age at surgery was 53.8 years. The mean tumor diameter was 59.2 mm (range 50-85 mm) with cavernous sinus involvement in 59.1% (13 of 22 patients). The tumor involved the prechiasmatic segment of the optic nerve in all patients, invaded the optic canal in 77.3% (17 of 22 patients), and caused visual impairment in 86.4% (19 of 22 patients). Total resection (Simpson Grade I or II) was achieved in 30.4% of surgeries (7 of 23); subtotal and partial resections were each achieved in 34.8% of surgeries (8 of 23). The main factor precluding total removal was cavernous sinus involvement. There were no deaths. The mean Glasgow Outcome Scale score was 4.8 (median 5) at a mean of 56 months of follow-up. Vision improved in 66.7% (12 of 18 patients) with consecutive neuroophthalmological examinations, was stable in 22.2% (4 of 18), and deteriorated in 11.1% (2 of 18). New deficits in cranial nerve III or IV remained after 8.7% of surgeries (2 of 23). CONCLUSIONS This modified surgical protocol has provided both a good extent of resection and a good neurological and visual outcome in patients with giant anterior clinoidal meningiomas.

Dynamics of circulating hypoxia-mediated miRNAs and tumor response in patients with high-grade glioma treated with bevacizumab

OBJECTIVE Bevacizumab is an antiangiogenic agent under investigation for use in patients with high-grade glioma. It produces a high rate of radiological response; however, this response should be interpreted with caution because it may reflect normalization of the tumor vasculature and not necessarily a true antitumor effect. The authors previously demonstrated that 4 hypoxia-mediated microRNAs (miRNA)-miR-210, miR-21, miR-10b, and miR-196b-are upregulated in glioma as compared with normal brain tissue. The authors hypothesized that the regulation and expression of these miRNAs would be altered in response to bevacizumab treatment. The object of this study was to perform longitudinal monitoring of circulating miRNA levels in patients undergoing bevacizumab treatment and to correlate it with tumor response. METHODS A total of 120 serum samples from 28 patients with high-grade glioma were prospectively collected prior to bevacizumab (n = 15) or temozolomide (TMZ; n = 13) treatment and then longitudinally during treatment. Quantification of the 4 miRNAs was evaluated by real-time polymerase chain reaction using total RNA extracted from the serum. At each time point, tumor response was assessed by Response Assessment in Neuro-Oncology criteria and by performing MRI using fluid attenuated inversion recovery (FLAIR) and contrast-enhanced images. RESULTS As compared with pretreatment levels, high levels of miR-10b and miR-21 were observed in the majority of patients throughout the bevacizumab treatment period. miR-10b and miR-21 levels correlated negatively and significantly with changes in enhancing tumor diameters (r = -0.648, p < 0.0001) in the bevacizumab group but not in the TMZ group. FLAIR images and the RANO assessment did not correlate with the sum quantification of these miRNAs in either group. CONCLUSIONS Circulating levels of miR-10b and miR-21 probably reflect the antiangiogenic effect of therapy, but their role as biomarkers for tumor response remains uncertain and requires further investigation.

Is a wake-up call in order? Review of the evidence for awake craniotomy

Awake craniotomy (AC) has been used in increasing frequency in the past few decades. It has mainly been used for resection of intrinsic tumors, but also, rarely, for other pathologies. The vast majority of reports specific to one pathology, however, have focused on resection of low grade glioma in the awake setting. Tumors in eloquent areas have mainly been resected when the patient is awake for the purpose of preservation of function. Motor function is the most documented, and most successfully preserved function. Other functions are harder to localize with direct electrical stimulation (DES), and thus more difficult to preserve. The success rate of DES localization correlates to the rate of function preservation. The effect of AC on extent of resection is inconsistent in the literature. Other functions, such as sensory and visuospatial recognition, have been protected during AC, but this is best performed in large, referral centers that have experience with the procedure. Other benefits to AC, such as cost-effectiveness and reduction in patient pain and anxiety, have also been reported.

Frontal glioblastoma multiforme may be biologically distinct from non-frontal and multilobar tumors

Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults and carries a grim prognosis. Lobar GBM, notably those localized to the frontal lobe, are generally more amenable to complete surgical resection, and may carry a better prognosis. The biology of differently localized GBM has been reported scarcely in terms of prognostic markers, including isocitrate dehydrogenase 1 (IDH1) mutation and O(6)-methylguanine-methyltransferase (MGMT) methylation. To our knowledge, there has been no evaluation in the literature of different proliferation indexes in different GBM locations in the brain. We performed a retrospective evaluation of our prospectively collected database to assess the rate of IDH1 positivity, MGMT methylation and Ki67 index for GBM located in the frontal lobes alone, lobar GBM in other supra-tentorial lobes and multilobar GBM. IDH1 mutated tumors were localized in the frontal lobes in 50.0%, whereas only 20.3% of IDH1 wild-type tumors were localized in the frontal lobe (p=0.006); MGMT methylated tumors were localized in the frontal lobe in 32.0% of the cases. Only 13.75% of the MGMT unmethylated tumors were localized to the frontal lobe (p=0.005); Tumors with higher Ki67 proliferation index were more likely to be localized in the frontal lobe (40.6% vs. 19.5%, p=0.019). This is the largest cohort of GBM assessed for these purposes in the literature. Frontal lobe GBMs may be intrinsically biologically distinct from GBM in other lobes and from multilobar tumors.

Review of controversies in management of non-benign meningioma.

Meningiomas are one of the most common brain tumors. World Health Organisation (WHO) Grade II and Grade III meningiomas are grouped together as non-benign meningioma (NBM). There are several controversies surrounding NBM management, including the significance of extent of resection and the efficacy of post-operative radiation and drug treatment. We reviewed the literature to develop recommendations for management of NBM. The questions we sought to answer were: Does gross total resection (GTR) improve patient outcome? Is radiation therapy (RT) warranted after complete or after incomplete resection of NBM? What drug therapies have been proven to improve outcome in patients with NBM? We found that GTR improves outcome in WHO Grade II meningioma, and should be attempted whenever considered safe. GTR correlates less closely to outcome in Grade III meningioma compared to subtotal resection (STR). Extreme measures to completely resect Grade III meningioma are not warranted. RT following GTR of Grade II meningioma does not improve patient outcome, and may be reserved for recurrence. RT improves outcome following STR of Grade II meningioma. RT improves outcome after resection of Grade III meningioma. No drug therapy has been shown to improve outcome in NBM. This review elucidates recommendations for some of the controversies involving NBM.

Four cases of spinal epidural angiolipoma

Spinal angiolipomas are uncommon benign tumours composed of mature fatty tissue and abnormal vascular elements, most commonly found within the posterior spinal epidural space. Most tumours are located within the mid-thoracic spine; in contrast thoracolumbar junction and purely lumbar angiolipomas are rare. We report a case series of four spinal angiolipomas, including a thoracolumbar junction and a purely lumbar tumour.

IDH1 mutation may not be prognostically favorable in glioblastoma when controlled for tumor location: A case-control study

Isocitrate dehydrogenase 1 (IDH1) mutation is a known prognostic factor in glioblastoma multiforme (GBM). It has been well documented that patients with IDH1 mutant (IDH1-mu) GBM have a better outcome compared to patients with IDH1 wild-type (IDH1-WT) GBM. IDH1-mu tumors have been shown to be more commonly located in the frontal lobe, and less likely to be in multiple lobes. It is unclear whether differential location is part of the prognostically favorable profile of these tumors. We performed a case-control study, matching IDH1-mu GBMs to IDH1-WT GBMs that are controlled for age, sex and tumor location. There were 21 IDH1-mu tumors and 21 matched IDH1-WT tumors. Age, sex and tumor location were matched between the two groups. After controlling for the factors described, the IDH1-mu tumors were more likely to be secondary GBM (61.9% secondary vs. 14.3%, p=0.004). There was an insignificant trend towards smaller tumor volume in the IDH1-mu group (28.13±6.56 vs. 41.8±7.33 cm3, p=0.173). Extent of surgical resection was similar in both groups (mean 84.49% vs. 89.89%, p=0.419). There was no survival advantage for IDH1-mu tumors when controlled for location: 25.2months overall survival for IDH1-mu patients and 23.6 for IDH1-WT patients, p=0.794. IDH1 mutation may provide part of its prognostic significance by differential localization of tumor, both making IDH1-mu tumors more amenable to gross total resection and placing these tumors in less eloquent areas, thereby lowering neurological morbidity.

Cerebral vasospasm and delayed ischaemic deficit following elective aneurysm clipping.

Although common after subarachnoid haemorrhage, cerebral vasospasm (CVS) and delayed ischaemic neurological deficit (DIND) rarely occur following elective clipping of unruptured aneurysms. The onset of this complication is variable and its pathophysiology is poorly understood. We report two patients with CVS associated with DIND following unruptured aneurysmal clipping. The literature is reviewed and the potential mechanisms in the context of patient presentations are discussed. A woman aged 53 and a man aged 70 were treated with elective clipping of unruptured middle cerebral artery aneurysms, the older patient also having an anterior communicating artery aneurysm clipped. The operations were uncomplicated with no intra-operative bleeding, no retraction, no contusion, no middle cerebral artery (MCA) temporary clipping, and no intra-operative rupture. Routine post-operative CT scan and CT angiogram showed that in both patients the aneurysms were excluded from the circulation and there was no perioperative subarachnoid blood. Both patients had no neurological deficit post-operatively, but on day 2 developed DIND and vasospasm of the MCA. Both patients had angiographic improvement with intra-arterial verapamil treatment. In one patient, this was done promptly and the patient made a complete recovery, but in the other, the diagnosis was delayed for more than 24hours and the patient had residual hemiparesis and dysphasia due to MCA territory infarction. CVS and DIND following treatment of unruptured aneurysms is a very rare event. However, clinicians should be vigilant as prompt diagnosis and management is required to minimise the risk of cerebral infarction and poor outcome.

First line direct access for transarterial embolization of a dural arteriovenous fistula: Case report and literature review

Intracranial dural arteriovenous fistulae (DAVF) are complex vascular malformations consisting of a pathological shunt located between meningeal arteries and drainage to dural venous sinuses and/or cerebral veins. We report an unusual anatomical variation, resulting in a DAVF forming between the superior sagittal sinus and an anomalous origin of the middle meningeal artery (MMA) arising from the left ophthalmic artery. We present an atypical case requiring mini-craniotomy for catheter access, as well as cannulation of extracranial arterial supply prior to embolization of a Cognard type IIa+b fistula. Due to structural variation, transarterial endovascular embolization was deemed too high risk owing to risk of permanent blindness. We present a technical note and literature review on the first documented case of combined endovascular and surgical intervention as first line treatment for embolization of an anomalous middle meningeal artery related fistula. Our approach provided adequate obliteration of the DAVF and may be an alternative way to treat DAVF, when traditional transarterial or transvenous approaches are deemed high risk for neurological deficit.

Pilomyxoid astrocytoma in the adult cerebellum

Pilomyxoid astrocytoma (PMA) is a recently recognised World Health Organization (WHO) Grade II tumour that was previously characterised as a subtype of the WHO Grade I pilocytic astrocytoma (PA). PMA has a histological appearance distinct from PA and a poorer prognosis due to its greater propensity for local recurrence and cerebrospinal dissemination. Although originally considered a paediatric tumour involving mainly the hypothalamic and chiasmatic region, reports of the lesion occurring in the adult population and other areas of the neuroaxis are emerging. We review the literature on PMA within the adult population and present the first case of PMA in the cerebellum of an adult female.