The ß- radio-guided surgery: Method to estimate the minimum injectable activity from ex-vivo test.

PURPOSE: Radio-guided surgery with ß- decays is a novel technique under investigation. One of the main advantages is its capability to detect small (⩽0.1 ml) samples after injecting the patient with low activity of radiopharmaceutical. This paper presents an experimental method to quantify this feature based on ex-vivo tests on specimens from meningioma patients. METHODS: Patients were enrolled on the basis of the standard uptake value (SUV) and the tumour-to-non-tumour activity ratio (TNR) resulted from 68Ga-DOTATOC PET exams. After injecting the patients with 93-167 MBq of 90Y-DOTATOC, 26 samples excised during surgery were analyzed with a ß- probe. The radioactivity expected on the neoplastic specimens was estimated according to the SUV found in the PET scan and the correlation with the measured counts was studied. The doses to surgeon and medical personnel were also evaluated. RESULTS: Even injecting as low as 1.4 MBq/kg of radiotracer, tumour residuals of 0.1 ml can be detected. A negligible dose to the medical personnel was confirmed. CONCLUSIONS: Radio-guided surgery with ß- decays is a feasible technique with a low radiation dose for both personnel and patient, in particular if the patient is injected with the minimum required activity. A correlation greater than 80% was observed between the measured counts and the expected activity for the lesion samples based on the individual SUV and the TNR. This makes identifiable the minimum injectable radiotracer activity for cases where 90Y is the utilized radionuclide.

First ex vivo validation of a radioguided surgery technique with ß-radiation.

PURPOSE: A radio-guided surgery technique with ß(-)-emitting radio-tracers was suggested to overcome the effect of the large penetration of γ radiation. The feasibility studies in the case of brain tumors and abdominal neuro-endocrine tumors were based on simulations starting from PET images with several underlying assumptions. This paper reports, as proof-of-principle of this technique, an ex vivo test on a meningioma patient. This test allowed to validate the whole chain, from the evaluation of the SUV of the tumor, to the assumptions on the bio-distribution and the signal detection. METHODS: A patient affected by meningioma was administered 300MBq of (90)Y-DOTATOC. Several samples extracted from the meningioma and the nearby Dura Mater were analyzed with a ß(-) probe designed specifically for this radio-guided surgery technique. The observed signals were compared both with the evaluation from the histology and with the Monte Carlo simulation. RESULTS: we obtained a large signal on the bulk tumor (105cps) and a significant signal on residuals of ∼0.2ml (28cps). We also show that simulations predict correctly the observed yields and this allows us to estimate that the healthy tissues would return negligible signals (≈1cps). This test also demonstrated that the exposure of the medical staff is negligible and that among the biological wastes only urine has a significant activity. CONCLUSIONS: This proof-of-principle test on a patient assessed that the technique is feasible with negligible background to medical personnel and confirmed that the expectations obtained with Monte Carlo simulations starting from diagnostic PET images are correct.

Feasibility of simultaneous sodium fluorescein and indocyanine green injection in neurosurgical procedures.

OBJECTIVE: The objective of this study is to assess the feasibility of simultaneous Sodium Fluorescein (SF) and Indocyanine Green (ICG) injection during neurosurgical procedures. PATIENTS AND METHODS: Three patients harboring a high-grade glioma (HGG) were retrospectively identified in the surgical database of the Neurosurgical Unit 2 at the Foundation IRCCS Istituto Neurologico C. Besta in Milan, by having received intraoperatively both SF for tumor resection and ICG for vasculature angiographic studies in the same surgical procedure. We identified 2 males and 1 female (age range 25-60). Lesions were located in the left temporo-polar area and hippocampus (1 case), right superior frontal gyrus (1 case), left supplementary motor area (1 case). All the three lesions showed Magnetic Resonance Imaging (MRI) characteristics of HGG and, for this reason, in all patients a fluorescein-guided tumor removal was proposed. In the same surgical procedure ICG videoangiography was considered necessary in order to study arterial and venous vasculature, given by the strict relation of the tumor with an unexpected Posterior Communicating Artery (PComA) aneurysm in one case and with cortical drainage veins complexes in the other two cases. In all cases a microscope equipped with both YELLOW560 and IR800 integrated filters (Pentero 900, Carl Zeiss, Oberkorchen, Germany) was used. Fluorescein was i.v. injected at a dose of 5mg/kg immediately after patient intubation. ICG was i.v. injected in bolus on demand of the operating surgeon at a dose of 12.5mg. RESULTS: No side-effects related to simultaneous injection of SF and ICG were identified. In all three cases, the use of SF allowed to better visualize the tumor areas during surgical removal, thus leading to a radical resection until no macroscopic appearance of residual tumor mass and no fluorescence was visible in the surgical cavity. ICG videoangiography confirmed the patency of branches of internal carotid artery after clipping of an unexpected small PComA aneurysm found intraoperatively during tumor removal in one case, while in patient 2 and 3 it allowed to evaluate patency and study flow pattern in cortical drainage veins that were intimately related to the tumors and the way of the surgical approach. Postoperative MRI showed a Gross Total Resection of the tumors in all cases. CONCLUSIONS: This study showed for the first time the feasibility of intravenous SF injection and ICG videoangiography in the same surgical procedure. The presence of different fluorescence filters on the same surgical microscope allows the surgeon to recognize and safely resect the tumor and simultaneously evaluate local brain vascularization.

A novel radioguided surgery technique exploiting ß(-) decays.

The background induced by the high penetration power of the radiation is the main limiting factor of the current radio-guided surgery (RGS). To partially mitigate it, a RGS with ß(+)-emitting radio-tracers has been suggested in literature. Here we propose the use of ß(-)-emitting radio-tracers and ß(-) probes and discuss the advantage of this method with respect to the previously explored ones: the electron low penetration power allows for simple and versatile probes and could extend RGS to tumours for which background originating from nearby healthy tissue makes probes less effective. We developed a ß(-) probe prototype and studied its performances on phantoms. By means of a detailed simulation we have also extrapolated the results to estimate the performances in a realistic case of meningioma, pathology which is going to be our first in-vivo test case. A good sensitivity to residuals down to 0.1 ml can be reached within 1 s with an administered activity smaller than those for PET-scans thus making the radiation exposure to medical personnel negligible.

Adult medulloblastoma: multiagent chemotherapy with cisplatinum and etoposide: a single institutional experience.

In 1991, a prospective phase II trial was initiated to evaluate the efficacy of treatment for adults with medulloblastoma (MB). After surgery, patients were staged with a neuroradiologic examination of the brain and neuroaxis and by cerebrospinal fluid cytology. All patients received three cycles of upfront cisplatinum (cisplatinum) and etoposide (VP16) chemotherapy followed by cranio-spinal radiation therapy. The current article reports on the long-term results from that trial. After a median follow-up of 14.9 years, among a total of 28 adults with MB, the overall progression-free survival and overall survival (OS) rates at 5 years were 57.6 and 80%, respectively. The median OS for the whole group of patients was 11.3 years. The observed toxicity was mainly hematological, with leukopenia and thrombocytopenia (16% of grades 3 and 4). In summary, in our small series of patients, the role of combination administration of CDDP + VP16 started before the initiation of radiotherapy in reducing recurrences, particularly distant recurrences, remains unclear. To know whether adding chemotherapy to craniospinal radiation in adult therapy increases relapse-free and overall survival, we must await the results of a larger randomized controlled clinical trial.

Application of intraoperative indocyanine green angiography for CNS tumors: results on the first 100 cases.

PURPOSE: To investigate the application of indocyanine green (ICG) videoangiography during microsurgery for central nervous system (CNS) tumors. METHODS: One hundred patients with CNS tumors who underwent microsurgical resection from December 2006 to December 2008 were retrospectively analyzed. The diagnosis was high grade glioma in 54 cases, low grade in 17 cases, meningioma in 14 cases, metastasis in 12 cases and hemangioblastoma in 3 cases. Overall, ICG was injected intraoperatively 194 times. The standard dose of 25mg of dye was injected intravenously and intravascular fluorescence from within the blood vessels was imaged through an ad hoc microscope with dedicated software (Pentero, Carl Zeiss Co., Oberkochen, Germany). Pre-resection and post-resection arterial, capillary and venous ICG videoangiographic phases were intraoperatively observed and recorded. RESULTS: ICG videangiography allowed for a good evaluation of blood flow in the tumoral and peritumoral exposed vessels in all cases. No side effects due to ICG were observed. CONCLUSIONS: ICG video-angiography is a significant method for monitoring blood flow in the exposed vessels during microsurgical removal of CNS tumors. Pre-resection videoangiography provides useful information on the tumoral circulation and the pathology-induced alteration in surrounding brain circulation. Post-resection examination allows for an immediate check of patency of those vessels that are closely related to the tumor mass and that the surgeon does not want to damage.

Expression of vascular endothelial growth factor receptor-1/-2 and nitric oxide in unruptured intracranial aneurysms.

The biological mechanisms associated with the development and rupture of intracranial aneurysms are not fully understood. To clarify the role of VEGF and the related receptors in the pathophysiology of aneurysm, immunostaining for VEGF, VEGFR1 and VEGFR2 was performed on specimens from six unruptured aneurysms and on two specimens of normal arteries wall as a control. The results were correlated with NO concentration of CSF collected during surgery from 8 patients affected by unruptured aneurysms and in 11 control patients. The immunohistochemical data showed a different pattern of VEGF/VEGFR1/VEGFR2 in aneurysms when compared with control. The results of this preliminary study suggest an imbalance of VEGF, VEGFR1 and VEGFR2, and the interaction of VEGF and NO in the pathophysiology of unruptured aneurysms. Our data support the hypothesis of aneurysm formation associated with a loss of expression of VEGFR1, moderate expression of VEGFR2 and high concentration of nitrate.

Endoscopic radial artery harvesting for U-clip EC-IC bypass in the treatment of a giant petrous internal carotid artery aneurysm: technical case report.

INTRODUCTION: High-flow extracranial-intracranial (EC-IC) bypass and aneurysm trapping constitutes a well-known surgical solution for internal carotid artery (ICA) aneurysms that are not amenable to clip ligation or endovascular therapy. The advantages of the radial artery (RA) as a conduit for myocardial revascularization have become widely accepted, with a better patency rate than that of the saphenous vein. CASE REPORT: A 66-year-old woman was found to harbour a right giant, partially thrombosed aneurysm of the intrapetrous segment of the internal carotid artery. Endoscopic harvesting of the RA was achieved combining a resterilizable retractor and a vessel sealing system. After neck dissection, the main trunk of the middle cerebral artery (MCA), its branches, and part of the aneurysm were isolated through a right fronto-orbito-zygomatic craniotomy. The external carotid artery, distal to the origin of the facial artery, was chosen in the neck for an end-to-end microanastomosis. The temporal branch of the MCA was selected for an end-to-side microanastomosis with the radial graft using ten U-clips. The total temporary occlusion time was 13 min. The post-operative course was uneventful. CONCLUSION: Endoscopic technique provides improved patient satisfaction, especially in terms of length of the surgical incision, when compared to the conventional approach. Combined with the innovative use of U-clips, this case illustrates how new technologies can simplify ECA-ICA bypass surgery while yielding a better cosmetic and functional outcome.

Self-closing Nitinol U-Clips for intracranial arterial microanastomosis: a preliminary experience on seven cases.

PURPOSE: To report experience on the use of self-closing nitinol U-Clips for different types of intracranial arterial microanastomosis. METHODS: We treated 7 patients (3 females and 4 males, age ranging from 25 to 68 yo) admitted from November 2005 to January 2008 to the Neurological Institute C. Besta of Milan. One patient had cerebral hypoperfusion and the others a complex intracranial aneurysm. In each patient a bypass procedure was completed by using self-closing Nitinol U-Clips for intracranial arterial microanastomoses. RESULTS: The total time of temporary occlusion was 15.71 +/- 4.386 min. Bypass patency was confirmed intraoperatively by near-infrared indocyanine green videoangiography and microdoppler in each patient. No spasm of the graft was encountered and immediate post-operative bypass patency was confirmed in 6/7 patients. The graft thrombosed in 1 patient with antiphospholipid syndrome. 1 patient died from a massive Subarachnoid Hemorrhage due to rupture of an aneurysm while waiting for an endovascular procedure. In the 5 patients at the last follow-up, long-term patency of the bypass was confirmed and no neurological deficits occurred related to the procedure. CONCLUSION: This is the first report of the use of U-Clips for intracranial microanastomosis. Our data indicated that it is a safe technique, reduces the time taken to perform an anastomosis and the risk of an ischemic complication. Further studies of the longer-term patency of bypass as performed with U-Clips are required.

Endoscopic radial artery harvesting for U-clip high-flow EC-IC bypass: technical report.

INTRODUCTION: Bypass and aneurysm trapping constitute a well-known surgical solution for aneurysms that are not suitable for clipping or coiling. New techniques are available that make EC-IC bypass procedures easier, safer and, possibly, less invasive. The nitinol self-closing U-Clip device (Medtronic, Inc., Minneapolis) has been designed to facilitate the interrupted suture technique by eliminating the need for suture management, knot tying, and surgical assistance. MATERIALS AND METHODS: We present two consecutive U-clip bypass procedures in which the radial artery graft was harvested endoscopically. RESULTS: This novel bypass technique employs endoscopy to minimise arm injury due to radial artery harvesting and self-closing U-clips to simplify the intracranial micro-anastomosis and reduce the temporary occlusion time. Angiography confirmed bypass patency in all patients. DISCUSSION: Combined with the innovative use of U-clips, these two examples illustrate how new technologies can simplify EC-IC bypass surgery while yielding a better cosmetic and functional outcome.

Use of self-closing U-clips for dural repair in mini-invasive surgery for herniated disc.

OBJECT: The feasibility of a new technique of dural repair (self-closing U-clips) in mini-invasive surgery for herniated disk is demonstrated in this case report. MATERIALS AND METHODS: A 44-year-old male patient underwent lumbar microdiscectomy at out Institute, with subsequent dural leak as surgical complication; the dural leak re-appeared even after a second intervention in which we used muscle and dural graft and fibrin glue to repair the leak. We then decided to employ self-closing nitinol- U-clip to achieve primary dural closure. RESULTS: After the intervention the patient no more presented signs or symptoms due to the unintended durotomy, and the postoperative course was uneventful. CONCLUSION: Self-closing nitinol U-clips (Medtronic, Inc., Minneapolis) can be used for closing a dural tear through a mini-invasive approach that could make a conventional microsuturing technique very difficult.

Chronic high frequency stimulation of the posteromedial hypothalamus in facial pain syndromes and behaviour disorders.

Chronic high frequency stimulation (HFS) of the posteromedial hypothalamus (PMH) has been the first direct therapeutic application of functional neuroimaging data in a restorative reversible procedure for the treatment of an otherwise refractory neurological condition; in fact, the target coordinates for the stereotactic implantation of the electrodes have been provided by positron emission tomography (PET) studies, which were performed during cluster headache attacks. HFS of PMH produced a significant and marked reduction of pain attacks in patients with chronic cluster headache (CCH) and in one patient with short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT). The episodes of violent behaviour and psychomotor agitation during the attacks of CCH supported the idea that the posteromedial hypothalamus could be also involved in the control of aggressiveness; this has been previously suggested, in the seventies, by the results obtained in Sano's hypothalamotomies for the treatment of abnormal aggression and disruptive behaviour. On the basis of these considerations, we have performed HFS of the PMH and controlled successfully violent and disruptive behaviour in patients refractory to the conventional sedative drugs. Finally, we also tested the same procedure in three patients with refractory atypical facial pain, but unfortunately, they did not respond to this treatment.

Gravity-aided trans-falcine removal of a contralateral subcortical ependymoma.

The transfalcine approach is a variant of the interhemispheric approach which provides exposure of the medial surface of the contralateral hemisphere through a falx incision. Gravity can be used as a natural retractor. We report a 32-year-old woman with an ependymoma of the medial surface of the left Rolandic area that was completely removed through a contralateral gravity-aided, image-guided transfalcine approach. The contralateral transfalcine approach can be a good option for lesions presenting at the interhemispheric fissure especially those associated with perilesional oedema and avoids the risks of a transparenchymal dissection and retraction of a swollen hemisphere.

Obliteration of a giant fusiform carotid terminus-M1 aneurysm after distal clip application and extracranial-intracranial bypass. Case report.

Giant intracranial aneurysms may not be amenable to direct surgical clipping or endovascular coiling because of three critical factors: 1) lack of clear aneurysmal neck; 2) giant size; 3) involvement with critical perforating or branch vessels. Techniques of flow redirection, however, may offer an alternative treatment strategy for these difficult lesions. In this paper, we report on the use of this alternative strategy in the successful treatment of a left giant fusiform carotid terminus-M1 aneurysm in a 16 year-old boy suffering from Ehler-Danlos disease. This patient was admitted to our Institution because his aneurysm was continuing to be increasing in size, despite a previous ligation of his left cervical ICA which was performed at another institution 2 years earlier after the patient had experienced a hemorrhagic stroke. Upon admission, a neurological examination revealed a slight motor aphasia with mild right hemiparesis, remnant of the ancient stroke. Because of its size and the involvement with M1 perforating arteries, a direct aneurysm attack was deemed inadvisable. After an initial ECA-ICA high flow bypass which spontaneously thrombosed, we performed a repeated high flow bypass with the application of a single clip on M1, right distal to the fusiform dilatation. After an uneventful postoperative course, we were unable to observe any new neurological deficits after surgery. A CT scan on postoperative day 1 revealed that the aneurysm had undergone a spontaneous thrombosis which was completely obliterated at the time of a 6-month follow-up angiogram. At that time, the ECA-ICA bypass was found to be patent. In conclusion the alternative of flow alteration strategies can be successfully used in the treatment of aneurysms that cannot be safely trapped or occluded by traditional neurosurgical methods.

Cerebral cavernomas and seizures: a retrospective study on 163 patients who underwent pure lesionectomy.

The objective was to evaluate the outcome of microsurgical "pure" lesionectomy in patients with supratentorial cavernous angiomas presenting with seizures. For this retrospective study 163 patients with cavernoma-related epileptic seizures were selected. They all underwent surgery in a single institution between 1988 and 2003. A microsurgical frame/frameless guided minimally invasive transulcal "pure" lesionectomy was performed. The haemosiderin stained gliotic brain parenchyma that was usually found surrounding the lesion was not removed. Among the 99 patients with epilepsy and longer clinical history, 68 (68.7%) were found completely to be seizure-free, 10 (10.1%) presented sporadic and less frequent seizures and 17 (17.1%) remained unchanged. Sixty-three out of 64 (98.4%) patients who experienced only single or sporadic seizures were found to be completely seizure-free after surgery. Five patients were lost at follow-up (mean 48 months, range 0.5-14 years). Long-term morbidity was 1.8%. Mortality was null. No haemorrhagic episodes were observed during follow-up. Pure lesionectomy prevents bleeding and development of epilepsy in patients that receive early surgery after the epileptic onset. In most of the epileptic patients with a good concordance between the electroclinical data and the location of the angioma, good results can be achieved by this kind of surgery so that more invasive and costly studies to find and remove the epileptogenic cerebral parenchyma seem justified only after lesionectomy fails.

Deep brain stimulation as a functional scalpel.

Since 1995, at the Istituto Nazionale Neurologico "Carlo Besta" in Milan (INNCB,) 401 deep brain electrodes were implanted to treat several drug-resistant neurological syndromes (Fig. 1). More than 200 patients are still available for follow-up and therapeutical considerations. In this paper our experience is reviewed and pioneered fields are highlighted. The reported series of patients extends the use of deep brain stimulation beyond the field of Parkinson's disease to new fields such as cluster headache, disruptive behaviour, SUNCt, epilepsy and tardive dystonia. The low complication rate, the reversibility of the procedure and the available image guided surgery tools will further increase the therapeutic applications of DBS. New therapeutical applications are expected for this functional scalpel.

The role of surgery in the treatment of typical and atypical facial pain.

Effective management of facial pain syndromes requires a correct clinical diagnosis. The temporal pattern of chronic pain is the most important aspect to be considered. It allows the identification of three groups of patients: (1) those who have paroxysmal pain, (2) those with mixed paroxysmal and constant pain, and (3) those with strictly constant pain. The less is the paroxysmal component, the more likely it seems to be that surgical intervention is useless or even dangerous. In particular, when the diagnosis is atypical facial pain, that is, a diffuse, nonanatomic orofacial pain of unknown pathophysiology, none of the surgical strategies that can cure trigeminal neuralgia should be used. Trigeminal neuralgia patients are often referred to neurosurgeons because of their well-known capability to obtain pain relief through many different procedures such as microvascular decompression, percutaneous balloon microcompression, thermorizotomy, drug injection within the trigeminal cistern and radiosurgery. Since all these procedure can cure patients with typical trigeminal neuralgia, the ideal algorithm of treatment is still under debate. We report on our 20 year-long experience with the surgical treatment of facial pain in general and trigeminal neuralgia in particular. Our treatment algorithm for trigeminal neuralgia is presented. Some ideas to offer a possible surgical help to patients with less typical, medically intractable, chronic facial pain are also given.

Huge epidural hematoma after surgery for spinal cord stimulation.

OBJECTIVE AND IMPORTANCE: Spinal epidural haematoma (SEH) following implantation of an epidural spinal cord electrode is a very rare complication but one that must not be overlooked. This case is unusual because of the almost "holocord" extension of the haematoma and the excellent recovery obtained by prompt surgical treatment. CLINICAL PRESENTATION: A 69 years old man with normal serum coagulation parameters was submitted to spinal cord stimulation (SCS) for chronic pain syndrome. After a minimal L1 laminotomy the patient developed paraplegia due to a large haematoma at D4-L2. INTERVENTION: Surgical removal of the entire clot by a D4-L2 laminectomy was performed immediately. CONCLUSION: Large epidural haematoma can result from SCS and this complication may be cured by appropriate and prompt surgery.