Intraoperative multi-exposure speckle imaging of cerebral blood flow.

Multiple studies have demonstrated that laser speckle contrast imaging (LSCI) has high potential to be a valuable cerebral blood flow monitoring technique during neurosurgery. However, the quantitative accuracy and sensitivity of LSCI is limited, and highly dependent on the exposure time. An extension to LSCI called multi-exposure speckle imaging (MESI) overcomes these limitations, and was evaluated intraoperatively in patients undergoing brain tumor resection. This clinical study ( n = 8) recorded multiple exposure times from the same cortical tissue area spanning 0.5-20 ms, and evaluated images individually as single-exposure LSCI and jointly using the MESI model. This study demonstrated that the MESI estimates provided the broadest flow sensitivity for sampling the flow magnitude in the human brain, closely followed by the shorter exposure times. Conservation of flow analysis on vascular bifurcations was used to validate physiological accuracy, with highly conserved flow estimates (<10%) from both MESI and 1 ms LSCI ( n = 14 branches). The MESI model had high goodness-of-fit with proper image calibration and acquisition, and was used to monitor blood flow changes after tissue cautery. Results from this study demonstrate that intraoperative MESI can be performed with high quantitative accuracy and sensitivity for cerebral blood flow monitoring.

Lumbar subdural hematoma from intracranial subarachnoid hemorrhage presenting with bilateral foot drop: case report.

BACKGROUND AND IMPORTANCE: We report a patient with lumbar subdural hematoma secondary to intracranial subarachnoid hemorrhage (SAH) presenting with bilateral foot drop and describe our management. CLINICAL PRESENTATION: A 37-year-old woman presented with grade 4 SAH and hydrocephalus requiring emergent external ventricular drainage. Angiography demonstrated a left vertebral artery dissection and pseudoaneurysm that was treated with embolization of the vertebral artery. Six days after admission, her neurologic examination significantly improved. She was awake, alert, following commands, and moving all her extremities normally except for bilateral foot drop. An MRI scan revealed a lumbar subdural hematoma with severe thecal sac compression at L4-S1. The patient was initially treated with expectant management followed by surgery after she demonstrated only modest improvement. Evacuation of the hematoma was undertaken by an L5-S1 laminectomy and drainage of the liquefied clot in the subdural, extra-arachnoid space. Postoperatively, the patient demonstrated improved strength in all muscle groups except for left lower extremity eversion. CONCLUSION: We present a case of subdural hematoma that caused bilateral foot drop. Neurologic improvement occurred after evacuation of the hematoma.

Embolization of skull base meningiomas and feeding vessels arising from the internal carotid circulation.

BACKGROUND: Practice patterns regarding the preoperative embolization of skull base tumors vary widely among institutions and are driven by surgeon preference and concerns about safety. OBJECTIVE: We present a recent experience at our institution with a specific focus on procedural decision-making, embolization of vessels arising from the internal carotid circulation, and complication rates. METHODS: During a 7.5-year period, 262 meningiomas were referred for embolization. of which 119 (45%) originated from the skull base. Tumors were categorized by location, feeding artery origin, and arteries embolized. Complication rates were reviewed. RESULTS: Sixty-four of 119 patients with skull base tumors (54%) underwent embolization of at least 1 feeding artery. Feeding arteries arose from the external carotid artery (ECA) circulation in 26 (22%), the internal carotid artery (ICA) circulation in 30 (25%), a combination of ECA/ICA/Vert in 54 (45%), and had only pial supply in 10 (8%). In total, 15 of 85 (18%) ICA feeding vessels were embolized. This included 9 of 28 vessels from the meningohypopheseal trunk, 3 of 4 vessels from the anterior temporal artery, 1 of 35 vessels from the ophthalmic artery, 1 of 8 vessels directly from the ICA, and 1 of 5 vessels from the inferolateral trunk. Complete devascularization occurred in 6 of 64 patients; subtotal devascularization was seen in 58 of 64. The overall angiographic complication rate for all meningiomas embolized in the study period was 2.5% (5/199). None of the complications occurred in the skull base group. CONCLUSION: Preoperative embolization of skull base meningiomas and ICA feeding vessels can be done with low complication rates when intraprocedural decision-making favors complication avoidance over complete devascularization.

Implications for immunotherapy of tumor-mediated T-cell apoptosis associated with loss of the tumor suppressor PTEN in glioblastoma.

The ability of glioma cells to escape the immune system remains a significant barrier to successful immunotherapy. Here we demonstrate that loss of the PTEN tumor suppressor gene, with associated activation of the PI3K/Akt/mTOR pathway, leads to a human glioma phenotype that induces autologous T-cell apoptosis upon contact. The PTEN status of pathologically confirmed glioblastoma specimens was defined, and primary cultures established after surgical resection of tumor from 26 patients. Autologous T-cells were isolated from these patients, and after T-cell activation was induced, these cells were co-cultured with matched autologous glioma cells, either alone, or after treatment with one of three inhibitors of the PI3K/Akt/mTOR pathway. When co-cultured with autologous T-cells, PTEN wild-type tumor cells induced apoptosis in a minimal number of activated T-cells (6-12% of T-cells), whereas tumors with PTEN loss induced much more profound levels of T-cell apoptosis (42-56% of T-cells). Prior treatment of PTEN-deficient tumor cells with specific inhibitors of the PI3K/Akt/mTOR pathway diminished T-cell apoptosis to levels seen after co-culture with wild-type PTEN tumor cells, suggesting that PTEN loss confers this immunoresistant phenotype through the PI3K/Akt/mTOR pathway. These results suggest that PTEN-deficient glioblastoma patients are suboptimal candidates for immunotherapy. In addition, our results raise the possibility of combining T-cell based immunotherapy protocols with clinical inhibitors of the PI3K/Akt/mTOR pathway.

Surgical resection and adjuvant radiotherapy for a large pineal hemangiopericytoma.

Hemangiopericytoma of the pineal region is exceedingly rare. We describe a patient with a large pineal region hemangiopericytoma who underwent a third ventriculostomy followed by a gross total resection by a unilateral interhemispheric approach with adjuvant radiotherapy. The patient remains recurrence free 4 years after treatment.

Multiple intracranial aneurysms and moyamoya disease associated with microcephalic osteodysplastic primordial dwarfism type II: surgical considerations.

Microcephalic osteodysplastic primordial dwarfism type II (MOPD II) is a rare genetic syndrome characterized by extremely small stature and microcephaly, and is associated in 25% of patients with intracranial aneurysms and moyamoya disease. Although aneurysmal subarachnoid hemorrhage and stroke are leading causes of morbidity and death in these patients, MOPD II is rarely examined in the neurosurgical literature. The authors report their experience with 3 patients who presented with MOPD II, which includes a patient with 8 aneurysms (the most aneurysms reported in the literature), and the first report of a patient with both moyamoya disease and multiple aneurysms. The poor natural history of these lesions indicates aggressive microsurgical and/or endovascular therapy. Microsurgery, whether for aneurysm clip placement or extracranial-intracranial bypass, is challenging due to tight surgical corridors and diminutive arteries in these patients, but is technically feasible and strongly indicated when multiple aneurysms must be treated or cerebral revascularization is needed.

Gamma interferon-mediated superinduction of B7-H1 in PTEN-deficient glioblastoma: a paradoxical mechanism of immune evasion.

B7 homolog 1 (B7-H1) is a recently discovered immunoresistance protein that is regulated posttranscriptionally after PTEN loss in malignant glioma, a deadly form of brain tumor. Here, the impact of gamma-interferon-mediated activation of B7-H1 was investigated in glioblastoma patients with PTEN loss. Lymphocytes and T cells were selected for apoptosis assays after 1 : 1 coculture with autologous glioma cells. Gamma interferon treatment of PTEN-deficient tumors resulted in superinduction of B7-H1 protein that correlated with increased T-cell apoptosis, an effect dependent upon activation of the PI3-kinase pathway. The combination of PTEN loss and gamma-interferon exposure in glioblastoma patients results in an exceptionally immunoresistant phenotype that may negate adaptive immunity through induction of T-cell apoptosis.

Temporal fossa hemangiopericytoma: a case series.

OBJECTIVE: Review clinical experience with temporal fossa hemangiopericytomas (HPCs). STUDY DESIGN: Retrospective case series review. SETTING: Tertiary referral center. PATIENTS: Intracranial HPCs within the temporal fossa. INTERVENTIONS: Craniotomy for either subtotal or gross total tumor excision. MAIN OUTCOME MEASURES: Determination of clinical outcome (alive with no evidence of disease, alive with disease, and died of disease). RESULTS: Five cases of HPC involving the temporal fossa were treated at our tertiary referral center for the period from 1995 to 2008. All but 1 patient were men. The age of presentation ranged from 31 to 62 years, and duration of follow-up ranged from 8 to 153 months. Clinical presentation was protean; headache was the most common symptom. Gross total tumor excision was achieved in 2 patients, whereas subtotal tumor excision was achieved in 3 patients. Reasons for subtotal resection included excessive intraoperative blood loss and inextricable tumor. Histologically, all tumors were composed of tightly packed, randomly oriented (jumbled-up) tumor cells with little intervening collagen. CD34 staining mostly highlighted the vascular background. One patient died of disease, 2 patients were alive with disease, and 2 patients had no evidence of disease. CONCLUSION: Management of temporal fossa HPC is challenging because clinical presentation is often late, and extent of tumor excision is constrained by vital structures in the cranial base and intracranial contents. A multidisciplinary approach with neurosurgery and neurotology undertaken to achieve the most complete tumor resection possible, whereas minimizing morbidity are likely to confer a longer period of symptom-free survival and improves curability of these difficult lesions.

Microsurgical management of incompletely coiled and recurrent aneurysms: trends, techniques, and observations on coil extrusion.

OBJECTIVE: With the growing volume of aneurysms treated with endovascular methods and the unavoidable risks of incomplete coiling or recurrence, the volume of coiled aneurysms requiring surgical management is growing. We present a consecutive surgical experience with previously coiled aneurysms to examine clinical trends, the phenomenon of coil extrusion, microsurgical techniques, and morphological features affecting clippability. METHODS: During a 10-year period, 43 patients underwent surgical management of an incompletely coiled or recurrent aneurysm (Gurian group B). Most patients (88%) presented initially with subarachnoid hemorrhage, most commonly (28%) located in the anterior communicating artery, and 42% of aneurysms were large or giant sized. RESULTS: Twenty-one patients had incompletely coiled aneurysms and 22 patients had recurrent aneurysms, with a mean time to recurrence of 28 months. Coil extrusion was observed in 1 of the incompletely coiled (5%) and 12 of the recurrent aneurysms (55%). Overall, 33 aneurysms were clipped directly, 7 unclippable aneurysms were bypassed, and 3 were wrapped. Three patients died (surgical mortality, 7%), 1 patient (2%) experienced permanent neurological morbidity, and the remaining 39 patients (91%) had good outcomes (mean follow-up, 4.3 years). CONCLUSION: This study demonstrated a sharp increase in the incidence of coiled aneurysms requiring surgery, reflecting the increasing numbers of patients opting for endovascular therapy initially. Coil extrusion occurs more often than expected, is often misdiagnosed on angiography as simply compaction, and seems to be a time-dependent process not seen acutely. Direct clipping is the preferred microsurgical treatment of coiled aneurysms and may be predicted by the relationship between coil width and compaction height (C/H < 2.5, or a wedge angle < 90 degrees). We recommend a bypass strategy for unclippable coiled aneurysms because it can be executed methodically; has predictable ischemia times; and is associated with more favorable results than thrombectomy, coil extraction, and clip reconstruction.

Flow cytometry and in vitro analysis of human glioma-associated macrophages. Laboratory investigation.

OBJECT: To date, glioma immunotherapy has been focused mostly on stimulating antitumor peripheral lymphocyte responses; however, some data suggest that microglia and/or macrophages (not lymphocytes) are the predominant inflammatory cells infiltrating gliomas. To study this hypothesis further, the authors analyzed inflammatory cell infiltrates in fresh human malignant glioma specimens and primary cultures. METHODS: Single-cell suspensions from fresh operative malignant glioma specimens, obtained by stereotactic localization, were analyzed for CD11b and CD45 by using flow cytometry. A comparison was made with peripheral blood mononuclear cells. In a subset of patients, a more detailed flow cytometry analysis of Class I and II major histocompatibility complex, B7-1, B7-2, CD11c, and CD14 expression was performed. Macrophage-like cells in primary glioma cultures were similarly assessed. RESULTS: Operative samples were obtained from 9 newly diagnosed malignant gliomas. The mean percent of CD45(+)/CD11b(-) cells (lymphocytes) was 2.48% (range 0.65-5.50%); CD45(dim)/CD11b(+) cells (microglia), 1.65% (range 0.37-3.92%); and CD45(bright)/CD11b+ (monocytes/macrophages), 6.25% (range 1.56-15.3%). More detailed fluorescence-activated cell sorting suggested that macrophage-like cells expressed Class I and II major histocompatibility complex, B7-2, and CD11c but not CD14 or B7-1. Primary human glioma cultures contained significant numbers of macrophage-like (CD45(bright)/CD11b(+)) cells, but these cells were lost with successive passages. These cells maintained the immunomarker profiles of macrophage-like cells from fresh specimens only if they were cultured in serum-free media. CONCLUSIONS: The CD45(+)/CD11b(+) cells are the predominant inflammatory cell infiltrating human gliomas. Of this type, the CD45(bright)/CD11b(+) cells, a phenotype compatible with circulating macrophages in rodent models, and not microglia, are the most common. Their immunomarker profile is compatible with an immature antigen-presenting cell. They are present in primary glioma cultures but are lost in successive passages. Their role is enigmatic, and they may prove an important target for future glioma immunotherapy studies.

The supracarotid-infrafrontal approach: surgical technique and clinical application to cavernous malformations in the anteroinferior Basal Ganglia.

OBJECTIVE: Many symptomatic cavernous malformations deep in the anteroinferior basal ganglia are deemed to be inoperable and managed conservatively because transcortical, transsylvian-transinsular, and transcallosal approaches are unsuitable. We present an approach to these lesions through the supracarotid triangle, between ascending perforators, and through the basomedial frontal lobe. METHODS: The supracarotid-infrafrontal approach incorporates an orbitozygomatic craniotomy, wide microsurgical exposure of the supracarotid triangle, dissection of perforating arteries, and image-guided resection through the posterior part of the medial orbital gyrus and anterior perforated substance. RESULTS: During 10 years of surgical experience with 269 patients with cavernous malformations, 5 patients were identified with lesions in the basal ganglia that were resected completely using the supracarotid-infrafrontal approach. Transient neurological deficits were observed postoperatively in 2 patients, and all patients had excellent outcomes (modified Rankin Scale score of 0 or 1; mean duration of follow-up, 1.4 years). CONCLUSION: Cavernous malformations in the anteroinferior basal ganglia come to the brain surface directly behind the internal carotid artery bifurcation, and the supracarotid-infrafrontal trajectory best matches the lesions' axes. The surgical corridor runs between perforating arteries, but entrance into these lesions opens additional working space that is not normally present when the approach is used with aneurysms. Careful handling of crossing and ascending perforating arteries is critical, as is delicate dissection of the lesion's superior pole where it abuts the internal capsule.

Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma.

Cancer immunoresistance and immune escape may play important roles in tumor progression and pose obstacles for immunotherapy. Expression of the immunosuppressive protein B7 homolog 1 (B7-H1), also known as programmed death ligand-1 (PD-L1), is increased in many pathological conditions, including cancer. Here we show that expression of the gene encoding B7-H1 increases post transcriptionally in human glioma after loss of phosphatase and tensin homolog (PTEN) and activation of the phosphatidylinositol-3-OH kinase (PI(3)K) pathway. Tumor specimens from individuals with glioblastoma multiforme (GBM) had levels of B7-H1 protein that correlated with PTEN loss, and tumor-specific T cells lysed human glioma targets expressing wild-type PTEN more effectively than those expressing mutant PTEN. These data identify a previously unrecognized mechanism linking loss of the tumor suppressor PTEN with immunoresistance, mediated in part by B7-H1.

Solitary fibrous tumor arising from Cranial Nerve VI in the prepontine cistern: case report and review of a tumor subpopulation mimicking schwannoma.

OBJECTIVE: The authors present a report of a solitary fibrous tumor (SFT) arising from the intradural component of the VIth cranial nerve as it travels through the prepontine cistern. SFTs of the central nervous system are extremely rare entities that clinically masquerade as dural-based lesions, such as meningiomas or hemangiopericytomas. Because of their infrequency and clinical similarity to other central nervous system (CNS) lesions, diagnosis is largely dependent on pathological features. In this study, the authors define a subpopulation of SFTs that seem to arise directly from nerve, rather than meninges, and clinically mimic the appearance of a schwannoma. CLINICAL PRESENTATION: The patient was a 29-year-old woman with a several-month history of progressive right arm and leg numbness and mild hemiparesis, with the development of diplopia 2 weeks before admission. Outside imaging revealed a 3.9-cm mass in the prepontine cistern with extension into Meckel's cave and the cavernous sinus, resulting in significant brainstem compression. INTERVENTION: The patient underwent preoperative angiography with embolization of feeding vessels off of the left meningohypophyseal trunk. The patient was then taken to the operating room by a combined neurosurgical and ear, nose, and throat team, where the patient underwent a retrolabyrinthine/subtemporal craniotomy for tumor resection. During resection of the prepontine component, the tumor was identified as originating from the left Cranial Nerve VI as it traversed through the prepontine cistern. Resection of the tumor component involving the cavernous sinus and Meckel's cave was deferred for follow-up treatment with intensity-modulated radiation therapy. Pathological examination revealed tissue consistent with the diagnosis of SFT. CONCLUSION: SFTs involving the CNS are rare entities that are almost always diagnosed after tissue is obtained because of their clinical and radiographic similarity to meningiomas. This patient had an SFT masquerading as a VIth cranial nerve schwannoma. Although the natural history of SFTs in the CNS is not completely understood, correct diagnosis is important, given the rate of recurrence found in the more common pleural-based SFT and examples of CNS SFTs with malignant features.

Epidemiology and pathology of intraventricular tumors.

Tumors that primarily or exclusively involve the ventricular system constitute a rare and heterogeneous group. Certain histologic tumor types predominantly occur in children, whereas others are more common in adults. Tumor location provides additional clues to correct diagnosis. When used in conjunction with clinical and radiologic data, histopathologic features can distinguish among this wide range of possibilities to provide the correct diagnosis for optimal patient management.