Giorgio Gioffrè

Predictive value of intraoperative 5-aminolevulinic acid–induced fluorescence for detecting bone invasion in meningioma surgery

OBJECT Bone invasion is a major concern in meningioma surgery, since it is predictive of the recurrence of cranial involvement, morbidity, and mortality. Bone invasion has been reported in 20%-68% of studies with histopathologically confirmed data. Unfortunately, radical resection of bone invasion remains challenging. The aim of this study was to assess the role of 5-aminolevulinic acid (5-ALA) fluorescence in guiding the resection of bone-invading meningiomas. To this purpose, the sensitivity, specificity, and positive and negative predictive values of 5-ALA in detecting meningioma bone invasion were evaluated. METHODS Data from 12 patients affected by bone-invading meningiomas (7 with skull base and 5 with convexity meningiomas) who had undergone surgery with the assistance of 5-ALA fluorescence and neuronavigation between July 2012 and March 2013 at the Department of Neurosurgery of Padua were retrospectively analyzed. To evaluate the sensitivity and specificity of 5-ALA fluorescence in detecting meningioma tissue, a pathologist analyzed 98 surgical bone samples under blue light, according to different fluorescence patterns. Magnetic resonance images and CT scans were obtained pre- and postoperatively to determine the extent of bone invasion resection. RESULTS The rate of 5-ALA-induced fluorescence of both tumor and bone invasion was 100%. Based on the pathological examination of bone specimens, 5-ALA presented a sensitivity of 89.06% (95% CI 81.41%-96.71%) and a specificity of 100% in detecting meningioma bone invasion, while the positive and negative predictive values were 100% and 82.93% (95% CI 71.41%-94.45%), respectively. At the postoperative stage, MRI did not detect cases of meningioma bone invasion, whereas CT scans revealed residual hyperostosis in 2 cases. CONCLUSIONS In summary, 5-ALA fluorescence represents a suitable and reliable technique for identifying and removing bone infiltration by meningiomas. However, further studies are needed to prove the clinical consequences of this promising technique in a larger population.

Right parietal cortex and calculation processing: intraoperative functional mapping of multiplication and addition in patients affected by a brain tumor

OBJECT The role of parietal areas in number processing is well known. The significance of intraoperative functional mapping of these areas has been only partially explored, however, and only a few discordant data are available in the surgical literature with regard to the right parietal lobe. The purpose of this study was to evaluate the clinical impact of simple calculation in cortical electrostimulation of right-handed patients affected by a right parietal brain tumor. METHODS Calculation mapping in awake surgery was performed in 3 right-handed patients affected by high-grade gliomas located in the right parietal lobe. Preoperatively, none of the patients presented with calculation deficits. In all 3 cases, after sensorimotor and language mapping, cortical and intraparietal sulcus areas involved in single-digit multiplication and addition calculations were mapped using bipolar electrostimulation. RESULTS In all patients, different sites of the right parietal cortex, mainly in the inferior lobule, were detected as being specifically related to calculation (multiplication or addition). In 2 patients the intraparietal sulcus was functionally specific for multiplication. No functional sites for language were detected. All sites functional for calculation were spared during tumor resection, which was complete in all cases without postoperative neurological deficits. CONCLUSIONS These findings provide intraoperative data in support of an anatomofunctional organization for multiplication and addition within the right parietal area. Furthermore, the study shows the potential clinical relevance of intraoperative mapping of calculation in patients undergoing surgery in the right parietal area. Further and larger studies are needed to confirm these data and assess whether mapped areas are effectively essential for function.

Microsurgical clipping of intracranial aneurysms assisted by green indocyanine videoangiography (ICGV) and ultrasonic perivascular microflow probe measurement.

OBJECTIVES The purpose of this work is to assess the surgical and clinical outcome of intracranial aneurysm clipping performed combining the assistance of green indocyanine videoangiography (ICGV) and ultrasonic perivascular microflow probe. PATIENTS AND METHODS Data from patients affected with intracranial aneurysms who underwent microsurgical clipping assisted by both techniques between May 2012 and April 2013 were retrospectively evaluated. RESULTS 26 patients with 34 aneurysms (25 unruptured) were enrolled. In a total of 11 aneurysms (32%), the vascular clip needed repositioning, since either the post-clipping microprobe assessment detected a significant flow reduction of the explored vessels (8 cases, 23%) or ICGV identified a residual non-obliterated aneurysm (3 cases, 9%). A second clip repositioning was required in 3 cases (9%) because of dome remnant showed with ICGV. In all cases, final microprobe and ICGV assessments showed a complete exclusion of the aneurysm, without evidence of vascular flow impairment. Postoperatively, 1 patient (3%) presented a residual neck aneurysm. No permanent morbidity was reported. CONCLUSION With the limits of our small case series, our results testify that the presented approach may provide high exclusion rate in the treatment of cerebral aneurysm with very low morbidity in selected patients.

The endoscopic endonasal approach for cerebrospinal fluid leak repair in the elderly

INTRODUCTION Cerebrospinal fluid (CSF) rhinorrhea can lead to CNS infections, carrying significant morbidity and mortality, especially in the elderly. Endoscopic endonasal surgery is a validated technique in the repair of anterior skull base CSF leaks. The aim of this study is to assess diagnostic management, surgical technique and clinical outcome in a consecutive series of elderly patients. METHODS Patients older than 65 years treated for anterior skull base CSF leaks through endoscopic endonasal surgery between 2003 and 2014 were retrospectively reviewed. All patients underwent preoperative nasal endoscopy, laboratory and radiological assessment. In doubtful cases endoscopic exploration was performed after intrathecal fluorescein (IF) injection. Patients were discharged between 3 and 4 days after surgery, and the endoscopic follow-up ranged from 3 to 24 months. RESULTS 20 patients (age range 65-92) presented with 10 spontaneous and 10 traumatic/iatrogenic CSF leaks. In 40% of patients formal rhinoscopy and radiological assessment did not localize the CSF leak and IF injection was performed. IF enabled the identification of the skull base defect in all cases, with no adverse effects. In 11 cases the dura was repaired with fascia lata graft. All patients had successful endoscopic repair of the CSF fistula with no complications nor recurrences during follow-up. CONCLUSION Endoscopic endonasal surgery is a minimally invasive procedure for CSF leak treatment. In our experience, IF injection proved safe and efficient in detecting skull base defects not identified by preoperative imaging. Endoscopic endonasal surgery proved effective and reliable also in elderly patients, with short hospitalization times and no morbidity.

The "squeezing maneuver" in microsurgical clipping of intracranial aneurysms assisted by indocyanine green videoangiography.

BACKGROUND: Indocyanine green videoangiography (ICGV) is becoming routine in intracranial aneurysm surgery to assess intraoperatively both sac obliteration and vessel patency after clipping. However, ICGV-derived data have been reported to be misleading at times. We recently noted that a simple intraoperative maneuver, the “squeezing maneuver,” allows the detection of deceptive ICGV data on aneurysm exclusion and allows potential clip repositioning. The squeezing maneuver is based on a gentle pinch of the dome of a clipped aneurysm when ICGV documents its apparent exclusion. OBJECTIVE: To present the surgical findings and the clinical outcome of this squeezing maneuver. METHODS: Data from 23 consecutive patients affected by intracranial aneurysms who underwent the squeezing maneuver were analyzed retrospectively. The clip was repositioned in all cases when the dyeing of the sac was visualized after the maneuver. RESULTS: In 22% of patients, after an initial ICGV showing the aneurysm exclusion after clipping, the squeezing maneuver caused the prompt dyeing of the sac; in all cases, the clip was consequently repositioned. A calcification/atheroma of the wall/neck was predictive of a positive maneuver (P = .001). The aneurysm exclusion rate at postoperative radiological findings was 100%. CONCLUSION: With the limits of our small series, the squeezing maneuver appears helpful in the intraoperative detection of misleading ICGV data, mostly when dealing with aneurysms with atheromatic and calcified walls. ABBREVIATIONS: DSA, digital subtraction angiography ICG, indocyanine green ICGV, indocyanine green videoangiography

Intra-operative 5-aminolevulinic acid (ALA)-induced fluorescence of medulloblastoma: phenotypic variability and CD133+ expression according to different fluorescence patterns

Abstract5-Aminolevulinic acid (5-ALA) fluorescence has been proved advantageous in glioma surgery. Conflicting results have been reported by few studies published in literature about intra-operative 5-ALA-induced fluorescence of medulloblastoma (MDB). The aim of this study is to verify if these conflicting results could be explained by intra-tumoral histological and phenotypic differences. In the present case of a 45-year-old patient affected by a cerebellar MDB, histological analysis of cell phenotype and 5-ALA and CD133 correlation were performed in multiple samples according to different fluorescence patterns. Intra-operatively, the tumor appeared unevenly fluorescent under blue-violet light. Histologically, 5-ALA-intense biopsies from inner areas were characterized by a significant amount of cancer cells, whereas 5-ALA faint regions from peripheral areas displayed normal cerebellar features, with MDB cells infiltrating healthy tissues. Presenting our findings, we show the correlation between different 5-ALA fluorescence patterns of medulloblastoma with specific histological and phenotypical features. Thus, we hypothesize that a distinct relationship between CD133 expression and fluorescence accumulation presented in our study could partially explain the divergent results published in literature.

Transdural indocyanine green video-angiography of vascular malformations

BackgroundThe role of indocyanine green video-angiography (ICG-VA) in the surgical resection of vascular malformations has been largely described; conversely, the utility of ICG-VA before dural opening (transdural ICG-VA) in this situation remains unclear. The aim of this study is to present the application of transdural ICG-VA in a consecutive series of patients in order to explore the potential provided by a transdural visualisation of vascular malformations.MethodWe retrospectively analysed the application of intra-operative ICG-VA before dural opening in 15 consecutive patients who underwent surgical resection of vascular malformations. The cases included 12 cerebral arterio-venous malformations (AVMs), 2 cerebral dural arterio-venous fistulas (dAVFs) and 1 spinal arterio-venous fistula (AVF).ResultsICG-VA before dural opening allowed the visualisation of the site and extension of the malformation in 13 out of 15 cases, whilst arterial feeders and venous drainages were identified in 9 out of 15 cases. In two patients with dAVF, the point of fistula could be transdurally identified through ICG-VA. In 14% of cases, the size of bone flap designed on neuronavigation data was then modified according to transdural ICG-VA findings.ConclusionsTransdural ICG-VA proved an efficient tool that allows optimising the exposure of the malformation, performing a safe dural opening and identifying dural vascular connections of the lesion.

Open Transcranial Resection of Small (<35 mm) Meningiomas of the Anterior Midline Skull Base in Current Microsurgical Practice

OBJECTIVE Despite technical surgical advance, the ultimate management of midline anterior skull base meningiomas remains to be defined. Open transcranial surgery is usually the first treatment option for large meningiomas, while less invasive techniques such as endoscopic surgery or radiosurgery might represent an alternative to open microsurgery for smaller lesions. The aim of our study is to investigate the outcome of open transcranial microsurgery in the resection of small (<35 mm) meningiomas of the midline anterior cranial base. METHODS Clinical and surgical data from 43 patients affected by small midline anterior skull base meningiomas operated via an open transcranial approach were retrospectively reviewed. RESULTS The tumor diameter on its major axis ranged from 12 to 35 mm, with a mean diameter of 28 mm. Gross total resection (Simpson grades I-II) was achieved in 100% of cases through a pterional approach. Postoperative overall morbidity was 9%. It was 3% among patients <70 years. No mortality was reported. Postoperative visual outcome was significantly associated with preoperative visual performance (P = 0.02), but not with preoperative optic nerve compression as detected by magnetic resonance imaging (P = 0.116). Age >70 years was associated with postoperative visual impairment, although not significantly (P = 0.06). Visual function was preserved or improved in 95% of cases, in 100% of patients <70 years, and in 71% of patients with preoperative visual impairment. CONCLUSIONS In our experience, open transcranial surgery proved safe and effective for midline anterior skull base meningiomas smaller than 35 mm in all patients <70 years and in patients >70 years without preoperative visual deficit. Our data are consistent with the literature. Conversely, the standard of treatment for the subgroup of patients >70 years with preoperative visual deficit has not yet been defined. This specific subgroup of patients offers a topic for further investigation.

Original ArticleOpen Transcranial Resection of Small (<35 mm) Meningiomas of the Anterior Midline Skull Base in Current Microsurgical Practice

OBJECTIVE Despite technical surgical advance, the ultimate management of midline anterior skull base meningiomas remains to be defined. Open transcranial surgery is usually the first treatment option for large meningiomas, while less invasive techniques such as endoscopic surgery or radiosurgery might represent an alternative to open microsurgery for smaller lesions. The aim of our study is to investigate the outcome of open transcranial microsurgery in the resection of small (<35 mm) meningiomas of the midline anterior cranial base. METHODS Clinical and surgical data from 43 patients affected by small midline anterior skull base meningiomas operated via an open transcranial approach were retrospectively reviewed. RESULTS The tumor diameter on its major axis ranged from 12 to 35 mm, with a mean diameter of 28 mm. Gross total resection (Simpson grades I-II) was achieved in 100% of cases through a pterional approach. Postoperative overall morbidity was 9%. It was 3% among patients <70 years. No mortality was reported. Postoperative visual outcome was significantly associated with preoperative visual performance (P = 0.02), but not with preoperative optic nerve compression as detected by magnetic resonance imaging (P = 0.116). Age >70 years was associated with postoperative visual impairment, although not significantly (P = 0.06). Visual function was preserved or improved in 95% of cases, in 100% of patients <70 years, and in 71% of patients with preoperative visual impairment. CONCLUSIONS In our experience, open transcranial surgery proved safe and effective for midline anterior skull base meningiomas smaller than 35 mm in all patients <70 years and in patients >70 years without preoperative visual deficit. Our data are consistent with the literature. Conversely, the standard of treatment for the subgroup of patients >70 years with preoperative visual deficit has not yet been defined. This specific subgroup of patients offers a topic for further investigation.

Approaching a brainstem high-grade glioma (HGG) with the assistance of 5-aminolevulinic acid (5-ALA) technology: a new strategy for an old surgical challenge

Brainstem high-grade glioma (HGG) surgery remains challenging despite the assistance of neurophysiological monitoring, and presents remarkable morbidity (6.7–27.6 %) and mortality (1.3–16 %) rates [1]. Although the role of 5-aminolevulinic acid (5-ALA) assistance in high-grade gliomas surgery is well established, its application in the resection of brainstem gliomas has not yet been investigated. We report a case of a brainstem highgrade glioma we recently resected with the assistance of 5-ALA fluorescence and neurophysiological monitoring. The choice of intra-operative 5-ALA fluorescence assistance depended on the pre-operative radiological findings, showing a contrast enhancing tumor located at the lower brainstem (Fig. 1a). Informed consent was obtained. Three hours before induction of anesthesia, a dose of 20 mg/kg of 5-ALA (Medac GmbH, Hamburg, Germany) was administered orally. A neurosurgical microscope equipped with Blue 400 technology (Carl Zeiss, OPMI Pentero, Blue 400, Meditec, Germany) enabled the surgeon to switch from white xenon illumination to violet–blue excitation light during microneurosurgery. Our surgical attitude entailed the use of 5-ALA fluorescence to guide surgical resection until a motor (MEP) or somatosensory evoked potential (SSEP) amplitude decrease was recorded, or the presence of a lower cranial nerve nucleus/fascicle was detected by intra-operative electro-stimulation at tumor boundaries. Intra-operatively (Fig. 1b–e), the exofitic component of the lesion was clearly visible between the cerebellar tonsils, just before arachnoidal opening. The lesion appeared fluorescent under violet–blue light, enabling a tailored arachnoidal opening and assisting the dissection of the tumor from healthy tissues. The areas of intense pink enhancement, being identified as clearly pathological, were removed and sent to pathologist. The tumor was further removed under blue light using an ultrasonic dissector and with the assistance of neurophysiological monitoring. Although the ependymal tissue of the fourth ventricle showed a faint and uniform fluorescence, this was still considerably distinct from the bright fluorescence of the tumor. Fourth ventricle tela chorioidea and choroidal plexus were not fluorescent under blue light. Tumor resection was stopped after the complete resection of fluorescent tissue. The post-operative images showed no contrast enhancing tumor at MRI scans with gadolinium (Fig. 1f). The patient presented a post-operative dysphagia that completely recovered within 2 weeks. 5-ALA is a well-established tool in the current surgical management of high-grade glioma; it has been proved reliable and effective in both detecting tumor tissue and maximizing the extent of resection of supratentorial gliomas [2]. However, to our knowledge, to date there are no reports of the application of 5-ALA in the resection of brainstem high-grade glioma. We think that from the present case three main considerations can arise. Firstly, in our experience 5-ALA fluorescence was effective in assisting tumor resection. Indeed, it enabled early identification of tumor on brainstem surface thus guiding the correct surgical resection strategy. The sharp dissection between pathological and healthy tissue was helpful in guiding the successive tumor removal in this critical location. As far as the fluorescence pattern of tumor is concerned, the brainstem high-grade glioma showed the same fluorescence features as supratentorial high-grade gliomas. This is an interesting issue if we A. Della Puppa (&) O. Rustemi G. Gioffrè R. Scienza Department of Neurosurgery, Padua University Hospital, Azienda Ospedaliera di Padova, via Giustiniani, 2, 35128 Padua, Italy e-mail: alessandro.dellapuppa@sanita.padova.it