Long-term outcome of surgically treated and conservatively managed Rathke cleft cysts.

OBJECTIVE: Rathke cleft cysts (RCC) are benign lesions of the sellar region that require surgical treatment in case of visual deterioration or progression of the cyst. However, the natural course is often stable and asymptomatic. We aimed to investigate the characteristics of patients with cyst progression during follow-up (FU) and to compare the natural history of patients with RCC with patients who underwent surgery. METHODS: Patients with an MR morphologic cystic sellar lesion classified as RCC between 04/2001 and 11/2020 were included. Functional outcomes, including ophthalmologic, endocrinologic, and MRI data, were retrospectively analyzed and compared between surgically treated patients, patients on a "watch and wait" strategy (WWS), and patients on a WWS who underwent secondary surgery due to cyst progression. RESULTS: One hundred forty patients (median age 42.8 years) with RCC on MRI were identified. 52/140 (37.1%) underwent primary surgery. Of 88 patients (62.9%) with initial WWS, 21 (23.9%) underwent surgery for secondary cyst progression. Patients on the WWS had significantly smaller cyst volumes (p = 0.0001) and fewer visual disturbances (p = 0.0004), but a similar rate of hormone deficiencies (p = 0.99) compared with surgically treated patients preoperatively. Postoperatively patients suffered significantly more often from hormone deficiencies than WWS patients (p = 0.001). Patients who switched to the surgical group were significantly more likely to have preoperative T1 hyperintense signals on MRI (p = 0.0001) and visual disturbances (p = 0.001) than patients with continuous WWS. Postoperatively, these patients suffered more frequently from new hormonal deficiencies (p = 0.001). Endocrine and ophthalmologic outcomes in patients with primary and secondary surgery were comparable. Multivariate analysis showed that WWS patients were at a higher risk of requiring surgery for cyst progression when perimetric deficits (p = 0.006), hyperprolactinemia (p = 0.003), and corticotropic deficits (p = 0.005) were present. CONCLUSION: Surgical treatment of RCC may cause new hormonal deficiencies, which are rare in the natural course. Therefore, the indication for surgery should be carefully evaluated. Hyperprolactinemia and corticotropic deficits were significant indicators for a secondary cyst progression in patients with RCC. However, a significant amount of almost 25% of initially conservatively managed cysts showed deterioration, necessary for surgical intervention.

Nuclear translocation of beta catenin in patients with Rathke cleft cysts-clinical and imaging characteristics and risk of recurrence.

PURPOSE: Although Rathke cleft cysts (RCC) are benign lesions of the sellar region, recurrence is frequent after surgical treatment. Nuclear translocation of ß-catenin (NTßC), a key effector of the wnt-signaling pathway that is responsible for cell renewal, has been shown to act as a proto-oncogene and is considered to be a potential risk factor for increased recurrence in RCC. In this study, we analyzed a surgically treated cohort into patients with and without NTßC expression in order to identify clinical and imaging differences and further evaluate the risk of recurrence. METHODS: Patients with resection of RCC between 04/2001 and 11/2020 were included. Histological specimens were immunohistochemically stained for ß-catenin. Study endpoints were time to cyst recurrence (TTR) and functional outcome. Functional outcome included ophthalmological and endocrinological data. Furthermore, MRI data were assessed. RESULTS: Seventy-three patients (median age 42.3 years) with RCC underwent mainly transsphenoidal cyst resection (95.9%), 4.1% via transcranial approach. Immunohistochemical staining for ß-catenin was feasible in 61/73 (83.6%) patients, with nuclear translocation detected in 13/61 cases (21.3%). Patients with and without NTßC were equally likely to present with endocrine dysfunction before surgery (p = 0.49). Postoperative new hypopituitarism occurred in 14/73 (19.2%) patients. Preoperative visual impairment was equal in both groups (p = 0.52). Vision improved in 8/21 (33.3%) patients and visual field deficits in 22/34 (64.7%) after surgery. There was no difference in visual and perimetric outcome between patients with and without NTßC (p = 0.45 and p = 0.23, respectively). On preoperative MRI, cyst volume (9.9 vs. 8.2 cm3; p = 0.4) and evidence of hemorrhage (30.8% vs. 35.4%; p = 0.99) were equal and postoperative cyst volume decreased significantly in both groups (0.7 vs. 0.5 cm3; p < 0.0001 each). Cyst progression occurred in 13/73 (17.8%) patients after 39.3 ± 60.3 months. Cyst drainage with partial removal of the cyst wall resulted in improved recurrence-free survival without increasing the risk of complications compared with cyst fenestration alone. Patients with postoperative diabetes insipidus had an increased risk for recurrence according to multivariate analysis (p = 0.005). NTßC was evident in 4/15 patients (26.7%) and was not associated with a higher risk for recurrence (p = 0.67). CONCLUSION: Transnasal transsphenoidal cyst drainage with partial removal of the cyst wall reduces the risk of recurrence without increasing the risk of complications compared with fenestration of the cyst alone. Patients with postoperative diabetes insipidus seem to have an increased risk for recurrence. In contrast, NTßC was not associated with a higher risk of recurrence and did not provide stratification for clinically distinct patients.

A simple surgical technique for sellar closure after transsphenoidal resection of pituitary adenomas in the context of risk factors for cerebrospinal fluid leaks and meningitis.

OBJECTIVE: The transsphenoidal approach is the standard for most pituitary tumors. Despite low morbidity, postoperative CSF fistulas and meningitis are specific complications. Various surgical closure techniques for intraoperative CSF (iCSF) leak and sellar reconstruction have been described. For many years the authors have applied synthetic materials for iCSF leak repair and sellar closure in a standardized fashion in their department. Here they analyze the surgical outcome as well as risk factors for iCSF leak and meningitis. METHODS: All patients with transsphenoidal resection of a pituitary adenoma performed by the same surgeon between January 2013 and December 2019 were screened retrospectively. A small amount of iCSF flow without a diaphragmatic defect was classified as a minor leak, and obvious CSF flow with or without a diaphragmatic defect was classified as a major leak. In case of iCSF leak, a fibrin- and thrombin-coated sponge was used to cover the diaphragmatic defect and another one was used for the sellar opening. A gelatin sponge was placed in the sphenoid sinus as an abutment. The primary and secondary outcomes were the number of postoperative CSF (pCSF) leaks and meningitis, respectively. Clinical, histological, and perioperative data from medical records were collected to identify risk factors for CSF leak and meningitis. RESULTS: Of 417 transsphenoidal surgeries, 359 procedures in 348 patients with a median age of 54 years were included. There were 96 iCSF leaks (26.7%; 37.5% major, 62.5% minor). In 3 of 359 cases (0.8%) a pCSF fistula occurred, requiring revision surgery in 2 patients and a lumbar drain in 1 patient. Meningitis occurred in 3 of 359 cases (0.8%). All 3 patients recovered without sequelae after antibiotic therapy. According to univariate analysis, risk factors for iCSF leak were macroadenoma (p = 0.006) and recurrent adenoma (p = 0.032). An iCSF leak was found less often in functioning adenomas (p = 0.025). In multivariate analysis recurrent tumors remained as a risk factor (p = 0.021) for iCSF leak. Patients with iCSF leak were at increased risk for a pCSF leak (p = 0.005). A pCSF leak in turn represented the key risk factor for meningitis (p = 0.033). CONCLUSIONS: Patients with macroadenomas and recurrent adenomas are especially at risk for iCSF leak. An iCSF leak in turn increases the risk for a pCSF leak, which carries the risk for meningitis. The authors' surgical technique leads to a very low rate of pCSF leaks and meningitis without using autologous graft materials. Hence, this technique is safe and improves patient comfort by avoiding the disadvantages of autologous graft harvesting.

[Multidisciplinary management of clival chordoma]. / Interdisziplinäres Management von Clivuschordomen.

Chordoma of the clivus belong to the rare tumors of the skull base. Due to their aggresive behaviour including intradural infiltration of neurovascular structures an interdisciplinary treatment is mandatory. This article gives an overview on current surgical concepts including the endoscopic approach as well as the postoperative radiotherapy. Novel diagnostic tools and molecular targets to optimize individual tumor therapy are discussed.

The USP8 mutational status may predict long-term remission in patients with Cushing's disease.

OBJECTIVE: Almost half of the cases of Cushing's disease (CD) tumours carry recurrent activating somatic mutations in the ubiquitin-specific protease eight gene (USP8). The USP8 mutational status could predict remission in patients with CD, so our objective was to correlate the presence of somatic USP8 mutations with the rate of recurrence after transsphenoidal surgery (TSS) retrospectively. DESIGN: Biochemical, radiological and clinical data were retrospectively assessed in 48 patients. USP8 mutational status was determined from corticotroph tumour samples. Association between USP8 mutational status, remission and recurrence was investigated. PATIENTS: Patients with Cushing's disease from a single-centre cohort who underwent TSS between 1991 and 2012. MEASUREMENTS: Long-term remission and recurrence rate after TSS with at least 6 months follow-up. Biochemical, radiological and clinical data, including sex, age at diagnosis, tumour size and pre-operative hormonal levels. USP8 mutational status. RESULTS: Patients with USP8 mutant corticotroph tumours (18 of 48; 37%) were diagnosed significantly earlier (mean ± SD 46 ± 10 years vs 53 ± 11 years; P = 0.028) and presented with higher pre-operative 24-hour urinary-free cortisol levels (median IQR µg/24 hours 1174.0, 1184.5 vs 480.0, 405.3; P = 0.045). The incidence of recurrence in a 10-year follow-up was significantly higher in patients with USP8 mutant tumours after the initial remission (58% vs 18% P = 0.026). Recurrence appeared significantly earlier in these patients (months 70, 44-97 95% CI vs 102, 86-119 95% CI; P = 0.019). CONCLUSION: Recurrence appears to be more frequent and earlier after TSS in patients with USP8 mutant corticotroph tumours.

Cystic Craniopharyngiomas: Microsurgical or Stereotactic Treatment?

BACKGROUND: Prognosis and treatment of cystic craniopharyngiomas are poorly defined. OBJECTIVE: To analyze progression-free survival (PFS) and safety profile of cystic craniopharyngiomas undergoing resection or minimally invasive drainage procedures. We compared further outcome measurements for cystic and solid tumors undergoing resection to elucidate the impact of the initial tumor composition on both PFS and the toxicity profile. METHODS: All patients with craniopharyngiomas consecutively treated between 1999 and 2014 were included. A treatment decision in favor of microsurgery or stereotactic treatment was made interdisciplinarily. For stereotactic drainage, a catheter was implanted, allowing both permanent upstream (into ventricular spaces) and downstream (into prepontine cistern) drainage. Study endpoints were tumor progression, functional outcome, and treatment toxicity. Functional endocrinological and visual outcome analyses referred to data obtained preoperatively and 6 weeks after treatment. The Kaplan-Meier method was used for survival analysis. Prognostic factors were obtained from proportional hazard models. RESULTS: Seventy-nine patients were included. The distribution of clinical and tumor-related data was well balanced among patients with solid (n = 35) and cystic (n = 44) tumors and those undergoing microsurgical or stereotactic treatment. Cystic tumors had shorter PFS (5-year PFS: 53.6% vs 66.8%, P = .10) and needed significantly more therapeutic interventions, which was independent of the initial treatment mode. The endocrinological deterioration rate was high for both solid and cystic tumors after microsurgery (59.4% and 85.7%, respectively), whereas it was significantly lower for cystic tumors undergoing stereotactic treatment (23.1%, P < .001). CONCLUSION: Stereotactic bidirectional drainage of cystic craniopharyngiomas is effective and provides a better endocrinological outcome than conventional microsurgery.

Intracranial and intradural nasal polyposis after iatrogenic skull base defect: A case report.

We report the first case of an intracranial and intradural nasal polyposis occurring in a close topographical relation to a previous, iatrogenic anterior skull base defect. The tumour was resected and the skull base defect was closed transnasally by an interdisciplinary team. The histopathological report confirmed recurrent polyposis.

Orbit-associated tumors: navigation and control of resection using intraoperative computed tomography.

OBJECT Treatment of skull base lesions is complex and usually requires a multidisciplinary approach. In meningioma, which is the most common tumor entity in this region, resection is considered to be the most important therapeutic step to avoid tumor recurrence. However, resection of skull base lesions with orbital or optic nerve involvement poses a challenge due to their anatomical structure and their proximity to eloquent areas. Therefore the main goal of surgery should be to achieve the maximum extent of resection while preserving neurological function. In the postoperative course, medical and radiotherapeutic strategies may then be successfully used to treat possible tumor residues. Methods to safely improve the extent of resection in skull base lesions therefore are desirable. The current study reports the authors' experience with the use of intraoperative CT (iCT) combined with neuronavigation with regard to feasibility and possible benefits of the method. METHODS Those patients with tumorous lesions in relationship to the orbit, sphenoid wing, or cavernous sinus who were surgically treated between October 2008 and December 2013 using iCT-based neuronavigation and in whom an intraoperative scan was obtained for control of resection were included. In all cases a second iCT scan was performed under sterile conditions after completion of navigation-guided microsurgical tumor resection. The surgical strategy was adapted accordingly; if necessary, resection was continued. RESULTS Twenty-three patients (19 with WHO Grade I meningioma and 4 with other lesions) were included. The most common clinical symptoms were loss of visual acuity and exophthalmus. Intraoperative control of resection by iCT was successfully obtained in all cases. Intraoperative imaging changed the surgical approach in more than half (52.2%) of these patients, either because iCT demonstrated unexpected residual tumor masses or because the second scan revealed additional tumor tissue that was not detected in the first scan due to overlay by osseous tumor parts; in these cases resection was continued. In the remaining cases resection was concluded as planned because iCT verified the surgeon's microscopic estimation of tumor resection status. Postoperative visual outcome was favorable in more than 80% of patients. CONCLUSIONS Intraoperative CT allows control of resection in case of uncertainty and can help to improve the extent of maximal safe resection, especially in case of osseous tumor parts and masses within the orbit.

Long-term outcome of patients with WHO Grade III and IV gliomas treated by fractionated intracavitary radioimmunotherapy.

OBJECT: The aim in this study was to present long-term results regarding overall survival (OS), adverse effects, and toxicity following fractionated intracavitary radioimmunotherapy (RIT) with iodine-131- or yttrium-90-labeled anti-tenascin monoclonal antibody ((131)I-mAB or (90)Y-mAB) for the treatment of patients with malignant glioma. METHODS: In 55 patients (15 patients with WHO Grade III anaplastic astrocytoma [AA] and 40 patients with WHO Grade IV glioblastoma multiforme [GBM]) following tumor resection and conventional radiotherapy, radioimmunoconjugate was introduced into the postoperative resection cavity. Patients received 5 cycles of (90)Y-mAB (Group A, average dose 18 mCi/cycle), 5 cycles of (131)I-mAB (Group B, average dose 30 mCi/cycle), or 3 cycles of (131)I-mAB (Group C, 50, 40, and 30 mCi). RESULTS: Median OS of patients with AA was 77.2 months (95% CI 30.8 to > 120). Five AA patients (33%) are currently alive, with a median observation time of 162.2 months. Median OS of all 40 patients with GBM was 18.9 months (95% CI 15.8-25.3), and median OS was 25.3 months (95% CI18-30) forthose patients treated with the (131)I-mAB. Three GBM patients are currently alive. One-, 2-, and 3-year survival probabilities were 100%, 93.3%, and 66.7%, respectively, for AA patients and 82.5%, 42.5%, and 15.9%, respectively, for GBM patients. Restratification of GBM patients by recursive partitioning analysis (RPA) Classes III, IV, and V produced median OSs of 31.1, 18.9, and 14.5 months, respectively (p = 0.004), which was higher than expected. Multivariate analysis confirmed the role of RPA class, age, and treatment in predicting survival. No Grade 3 or 4 hematological, nephrologic, or hepatic toxic effects were observed; 4 patients developed Grade 3 neurological deficits. Radiological signs of radionecrosis were observed in 6 patients, who were all responding well to steroids. CONCLUSIONS: Median OS of GBM and AA patients treated with (131)I-mABs reached 25.3 and 77.2 months, respectively, thus markedly exceeding that of historical controls. Adverse events remained well controllable with the fractionated dosage regimen.

Endotracheal Tube Electrodes to Assess Vocal Cord Motor Function During Surgery in the Cerebellopontine Angle.

BACKGROUND: The 10th cranial nerve (CN X) is at risk during surgery in the lower cerebellopontine angle (CPA). OBJECTIVE: To evaluate endotracheal surface electrodes for assessment of CN X motor function during CPA surgery. METHODS: Twenty patients were enrolled. Electrophysiological recordings were analyzed and retrospectively correlated with clinical, imaging, and intraoperative data. RESULTS: Recordings from endotracheal surface electrodes were reliable and eligible for analyses in 17 patients; in 3 patients, no surface electrode compound motor action potentials (CMAPs) could be obtained. Those patients with sufficient recordings underwent surgery in the CPA for tumors in 14 patients and for nontumor pathologies in 3 patients. In 12 patients, bipolar stimulation of motor rootlets in the CPA resulted in simultaneous CMAPs recorded from both surface electrodes and needle electrodes placed in the soft palate. Coactivation was particularly seen in patients with an intricate relationship between lower cranial nerves and tumor formations (n = 9/10). Amplitudes and latencies of vocal cord CMAPs showed high interindividual but low intraindividual variability. Parameters were not well correlated with the type of surgery (tumor vs nontumor surgery) and lower CN anatomy (displaced vs undisplaced). In 2 patients, vocal cord CMAPs were lost during tumor surgery, which was associated with postoperative dysphagia and hoarseness in 1 patient. CONCLUSION: Endotracheal surface electrodes allow identification of vocal cord motor rootlets in the CPA. Worsening of CMAP parameters might indicate functional impairment. These aspects support the use of endotracheal surface electrodes in selected patients in whom the vagus nerve might be at risk during CPA surgery.

Increased 68Ga-DOTATATE uptake in PET imaging discriminates meningioma and tumor-free tissue.

UNLABELLED: Meningiomas are known to express somatostatin receptor 2 (SSTR2). PET using the SSTR2 analog (68)Ga-DOTATATE has recently been introduced for imaging of meningiomas. However, a systematic correlation between (68)Ga-DOTATATE uptake, SSTR2 expression, and histology (including tumor-free scar tissue) is still lacking. For elucidation, we conducted this prospective study. METHODS: Twenty-one adult patients with primary (n = 12) or recurrent (n = 9) meningiomas were prospectively enrolled. Preoperative MR imaging and (68)Ga-DOTATATE PET scans were fused and used for a spatially precise neuronavigated tissue-sampling procedure during tumor resection. Histopathologic diagnosis included immunohistochemical determination of SSTR2 expression. At each individual sampling site, the maximum standardized uptake value (SUVmax) of (68)Ga-DOTATATE was correlated with MR imaging findings, histology, and semiquantitative SSTR2 expression. RESULTS: One hundred fifteen samples (81 tumor, 34 tumor-free) were obtained. There was a significant positive correlation between SUVmax and SSTR2 expression. Receiver-operating characteristic analysis revealed a threshold of 2.3 for SUVmax to discriminate between tumor and nontumoral tissue. Regarding the detection of tumor tissue, PET imaging showed a higher sensitivity (90% vs. 79%; P = 0.049), with specificity and positive predictive values similar to MR imaging, for both de novo and recurrent tumors. CONCLUSION: (68)Ga-DOTATATE uptake correlates with SSTR2 expression and offers high diagnostic accuracy to delineate meningioma from tumor-free tissue even in recurrent tumors after previous therapy. Our findings substantiate an important role for (68)Ga-DOTATATE PET in meningioma management.

Time to recovery of adrenal function after curative surgery for Cushing's syndrome depends on etiology.

CONTEXT: Successful tumor resection in endogenous Cushing's syndrome (CS) results in tertiary adrenal insufficiency requiring hydrocortisone replacement therapy. OBJECTIVE: The aim was to analyze the postsurgical duration of adrenal insufficiency of patients with Cushing's disease (CD), adrenal CS, and ectopic CS. DESIGN: We performed a retrospective analysis based on the case records of 230 patients with CS in our tertiary referral center treated from 1983-2014. The mean follow-up time was 8 years. PATIENTS: We included 91 patients of the three subtypes of CS undergoing curative intended surgery and documented followup after excluding cases with persistent disease, pituitary radiation, concurrent adrenostatic or somatostatin analog treatment, and malignant adrenal disease. RESULTS: The probability of recovering adrenal function within a 5 years followup differed significantly between subtypes (P = .001). It was 82% in ectopic CS, 58% in CD and 38% in adrenal CS. In the total cohort with restored adrenal function (n = 52) the median time to recovery differed between subtypes: 0.6 years (interquartile range [IQR], 0.03-1.1 y) in ectopic CS, 1.4 years (IQR, 0.9-3.4 y) in CD, and 2.5 years (IQR, 1.6-5.4 y) in adrenal CS (P = .002). In CD the Cox proportional-hazards model showed that the probability of recovery was associated with younger age (hazard ratio, 0.896; 95% confidence interval, 0.822-0.976; P = .012), independently of sex, body mass index, duration of symptoms, and basal ACTH and cortisol levels. There was no correlation with length and extend of hypercortisolism or postoperative glucocorticoid replacement doses. CONCLUSIONS: Time to recovery of adrenal function is dependent on the underlying etiology of CS.

Male sex as a risk factor for the clinical course of skull base chordomas.

OBJECT: Chordomas of the skull base are rare and locally invasive and have a poor prognosis. The aim of this retrospective multicenter study was to evaluate the current pattern of care and clinical course and to identify prognostic factors. METHODS: A total of 47 patients (26 men; mean age 48.5 years) treated in 5 centers were included. Histology was centrally reviewed; additionally, semiquantitative N- and E-cadherin expression analysis was performed. Prognostic factors were obtained from multivariate regression models. For survival analysis the Kaplan-Meier method was used. RESULTS: The median follow-up period was 5.2 years. Complete resection, incomplete resection, and extended biopsy were performed in 14.9%, 80.9%, and 4.3% of patients, respectively. Surgical morbidity was not associated with extent of resection. Adjuvant radiation therapy was performed in 30 (63.8%) of 47 patients. The median progression-free survival (PFS) was 7.3 years. Complete resection prolonged median overall survival (OS) (p = 0.04). Male patients presented with worse PFS (4.8 years vs 9.8 years; p = 0.04) and OS (8.3 years vs not reached; p = 0.03) even though complete resection was exclusively achieved in the male subpopulation. Multivariate analysis confirmed male sex as the most important risk factor for tumor progression (p = 0.04) and death (p = 0.02). Age, duration of symptoms, initial Karnofsky Performance Scale score, brainstem compression, involvement of the petrous bone, infiltration of the dura mater, modality and dose of radiation therapy, and the E- and N-cadherin expression patterns did not gain prognostic relevance. CONCLUSIONS: In skull base chordomas, male patients bear a higher risk of progressive disease and death. Male patients might benefit from more aggressive adjuvant therapy and/or from a closer follow-up schedule.

Headache in patients with pituitary adenoma: clinical and paraclinical findings.

AIM: The aim of this article is to generate hypotheses for the mechanism of pituitary adenoma headache. PATIENTS AND METHODS: Fifty-eight patients with pituitary adenoma were prospectively analysed for prevalence and manifestation of tumour headache. Intrapersonal and neoplasm-associated risk factors were assessed. RESULTS: Twenty-four patients (41%) had tumour-attributed headache, seven had migraine-like, 11 tension-type headache-like headache, and three both. Cluster headache-like headache was found once, and two headaches remained unclassified. Tumour-attributed headache was associated with a positive history of headache (p = 0.03; OR 3.4), nicotine abuse (p < 0.01; OR 4.7), intake of acute headache medication (p = 0.04; OR 3.3), and a higher tumour proliferation indicated by a Ki67-labelling index (LI) >3% (p = 0.02; OR 11.0). For patients with migraine-like tumour-attributed headache, risk factors were younger age (p = 0.02), nicotine abuse (p < 0.01; OR 10.9), acute headache treatment (p < 0.01; OR 9.0), and Ki67-LI >3% (p = 0.03; OR 14.1). For tension-type headache-like headache, the main risk factor was a positive history of tension-type headache (p = 0.045; OR 5.6). CONCLUSION: Headache predisposition and local tumour effects might be important for the pathophysiology of pituitary adenoma headache and tumour headache in general.

Enhanced analysis of intracerebral arterioveneous malformations by the intraoperative use of analytical indocyanine green videoangiography: technical note.

In cerebral arterioveneous malformations (AVMs) detailed intraoperative identification of feeding arteries, nidal vessels and draining veins is crucial for surgery. Intraoperative imaging techniques like indocyanine green videoangiography (ICG-VAG) provide information about vessel architecture and patency, but do not allow time-dependent analysis of intravascular blood flow. Here we report on our first experiences with analytical indocyanine green videoangiography (aICG-VAG) using FLOW 800 software as a useful tool for assessing the time-dependent intraoperative blood flow during surgical removal of cerebral AVMs. Microsope-integrated colour-encoded aICG-VAG was used for the surgical treatment of a 38-year-old woman diagnosed with an incidental AVM, Spetzler Martin grade I, of the left frontal lobe and of a 26-year-old man suffering from seizures caused by a symptomatic AVM, Spetzler Martin grade III, of the right temporal lobe. Analytical ICG-VAG visualization was intraoperatively correlated with in situ micro-Doppler investigation, as well as preoperative and postoperative digital subtraction angiography (DSA). Analytical ICG-VAG is fast, easy to handle and integrates intuitively into surgical procedures. It allows colour-encoded visualization of blood flow distribution with high temporal and spatial resolution. Superficial major and minor feeding arteries can be clearly separated from the nidus and draining veins. Effects of stepwise vessel obliteration on velocity and direction of AVM blood flow can be objectified. High quality of visualization, however, is limited to the site of surgery. Colour-encoded aICG-VAG with FLOW 800 enables intraoperative real-time analysis of arterial and venous vessel architecture and might, therefore, increase efficacy and safety of neurovascular surgery in a selected subset of superficial AVMs.

Detailed imaging of the normal anatomy and pathologic conditions of the cavernous region at 3 Tesla using a contrast-enhanced MR angiography.

INTRODUCTION: The purpose of this study was to evaluate the potential of a high-resolution contrast-enhanced magnetic resonance angiography (CE-MRA) at 3 Tesla for the delineation of the cavernous sinus (CS) anatomy both under normal and under pathological conditions. METHODS: Fifteen patients without pathologies in the CS and ten patients with pituitary adenomas were included. The CE-MRA was performed on a 3-Tesla scanner and analyzed collaboratively by two readers. The cranial nerves (CNs) within the CS, namely CNIII, CNIV, CNV1, CNV2, and CNVI, were identified in both patient groups. In the adenoma patients it was also assessed whether and to which extend the adenoma invaded the CS and the spatial relationship between tumor and CNs was determined. RESULTS: In the patients with normal CS anatomy, CNIII could be identified in 100%, CNIV in 86.7%, and CNV1, CNV2, as well as CNVI in 100% of analyzed sides. Pituitary adenomas invaded the CS unilaterally (right side) in four patients, and bilaterally in six patients. In patients with adenomas, the CN could be identified and differentiated from the tumor in the following percentages: CNIII in 100%, CNIV in 70%, both CNV1 and CNV2 in 90%, and CNVI in 100%. In all these cases, the tumor-nerve spatial relationship could be visualized. CONCLUSIONS: 3-Tesla CE-MRA allows detailed imaging of the complex anatomy of the CS and its structures. In adenoma patients, it clearly visualizes the spatial relationship between tumor and CNs, and thus might be helpful to optimize presurgical planning.

Different microsurgical approaches to meningiomas of the anterior cranial base.

INTRODUCTION: Meningiomas of the anterior skull base show specific characteristics, which render them difficult to handle. These tumors include olfactory groove, supra- and parasellar, anterior sphenoid ridge, cavernous sinus, and spheno-orbital meningiomas. Tumor localization and size, encasement of important structures as well as the extent of dural attachment may influence the decision for an adequate approach. DISCUSSION: Various approaches to the anterior cranial fossa exist, each with corresponding advantages and disadvantages. Recently, endoscopic approaches have increasingly been used. In this review, the different approaches to meningiomas of the anterior cranial fossa in respect of anatomical issues, indications, and associated risks are discussed.

Intraoperative computed tomography angiography with computed tomography perfusion imaging in vascular neurosurgery: feasibility of a new concept.

OBJECT: In vascular neurosurgery, there is a demand for intraoperative imaging of blood vessels as well as for rapid information about critical impairment of brain perfusion. This study was conducted to analyze the feasibility of intraoperative CT angiography and brain perfusion mapping using an up-to-date multislice CT scanner in a prospective pilot series. METHODS: Ten patients with unruptured aneurysms underwent intraoperative scanning with a 40-slice sliding-gantry CT scanner. Multimodal CT acquisition was obtained in 8 patients consisting of dynamic perfusion CT (PCT) scanning followed by intracranial CT angiography. Two of these patients underwent CT angiography and PCT 2 times in 1 session as a control after repositioning cerebral aneurysm clips. In another 2 patients, CT angiography was performed alone. The quality of all imaging obtained was assessed in a blinded consensus reading performed by an experienced neurosurgeon and an experienced neuroradiologist. A 6-point scoring system ranging from excellent to insufficient was used for quality evaluation of PCT and CT angiography. RESULTS: In 9 of 10 PCT data sets, the quality was rated excellent or good. In the remaining case, the quality was rated insufficient for diagnostic evaluation due to major streak artifacts induced by the titanium pins of the head clamp. In this particular case, the quality of the related CT angiography was rated good and sufficient for intraoperative decision making. The quality of all 12 CT angiography data sets was rated excellent or good. In 1 patient with an anterior communicating artery aneurysm, PCT scanning led to a repositioning of the clip because of an ischemic pattern of the perfusion parameter maps due to clip stenosis of an artery. The subsequent PCT scan obtained in this patient revealed an improved perfusion of the related vascular territory, and follow-up MR imaging showed only minor ischemia of the anterior cerebral artery territory. CONCLUSIONS: Intraoperative CT angiography and PCT scanning were shown to be feasible with short acquisition time, little interference with the surgical workflow, and very good diagnostic imaging quality. Thus, these modalities might be very helpful in vascular neurosurgery. Having demonstrated their feasibility, the impact of these methods on patients' outcomes has now to be analyzed prospectively in a larger series.

Intraoperative computed tomography with integrated navigation system in a multidisciplinary operating suite.

OBJECTIVE: We report our preliminary experience in a prospective series of patients with regard to feasibility, work flow, and image quality using a multislice computed tomographic (CT) scanner combined with a frameless neuronavigation system (NNS). METHODS: A sliding gantry 40-slice CT scanner was installed in a preexisting operating room. The scanner was connected to a frameless infrared-based NNS. Image data was transferred directly from the scanner into the navigation system. This allowed updating of the NNS during surgery by automated image registration based on the position of the gantry. Intraoperative CT angiography was possible. The patient was positioned on a radiolucent operating table that fits within the bore of the gantry. During image acquisition, the gantry moved over the patient. This table allowed all positions and movements like any normal operating table without compromising the positioning of the patient. For cranial surgery, a carbon-made radiolucent head clamp was fixed to the table. RESULTS: Experience with the first 230 patients confirms the feasibility of intraoperative CT scanning (136 patients with intracranial pathology, 94 patients with spinal lesions). After a specific work flow, interruption of surgery for intraoperative scanning can be limited to 10 to 15 minutes in cranial surgery and to 9 minutes in spinal surgery. Intraoperative imaging changed the course of surgery in 16 of the 230 cases either because control CT scans showed suboptimal screw position (17 of 307 screws, with 9 in 7 patients requiring correction) or that tumor resection was insufficient (9 cases). Intraoperative CT angiography has been performed in 7 cases so far with good image quality to determine residual flow in an aneurysm. Image quality was excellent in spinal and cranial base surgery. CONCLUSION: The system can be installed in a preexisting operating environment without the need for special surgical instruments. It increases the safety of the patient and the surgeon without necessitating a change in the existing surgical protocol and work flow. Imaging and updating of the NNS can be performed at any time during surgery with very limited time and modification of the surgical setup. Multidisciplinary use increases utilization of the system and thus improves the cost-efficiency relationship.

Serial O-(2-[(18)F]fluoroethyl)-L: -tyrosine PET for monitoring the effects of intracavitary radioimmunotherapy in patients with malignant glioma.

PURPOSE: Intracavitary radioimmunotherapy (RIT) offers an effective adjuvant therapeutic approach in patients with malignant gliomas. Since differentiation between recurrence and reactive changes following RIT has a critical impact on patient management, the aim of this study was to analyse the value of serial O-(2-[(18)F]fluoroethyl)-L: -tyrosine (FET) PET scans in monitoring the effects of this locoregional treatment. METHODS: Following conventional therapy, 24 glioma patients (5 WHO III, 19 WHO IV) underwent one to five RIT cycles with either (131)I-labelled (n=19) or (188)Re-labelled (n=5) anti-tenascin antibodies. Patients were monitored with serial FET PET scans (2-12 scans). For semiquantitative evaluation, maximal tumoural uptake (TU(max)) was evaluated and the ratio to background (BG) was calculated. Results of PET were correlated with histopathological findings (n=9) and long-term clinical follow-up for up to 87 months. RESULTS: In seven tumour-free patients, PET revealed slightly increasing but homogeneous FET uptake surrounding the resection cavity with a peak up to 18 months following RIT (TU(max)/BG 2.07+/-0.25) but stable or decreasing values during further follow-up (last follow-up: TU(max)/BG 1.63+/-0.22). Seventeen patients developed regrowth of residual tumour/tumour recurrence showing additional nodular FET uptake (TU(max)/BG 2.79+/-0.53). A threshold value of 2.4 (TU(max)/BG) allowed best differentiation between recurrence and reactive changes (sensitivity 82%, specificity 100%). CONCLUSION: FET PET is a sensitive tool for monitoring the effects of locoregional RIT. Homogeneous, slightly increasing FET uptake around the tumour cavity with a peak up to 18 months after RIT, followed by stable or decreasing uptake, points to benign, therapy-related changes. In contrast, nodular uptake is a reliable indicator of recurrence.