Object Fluorescein, a dye that is widely used as a fluorescent tracer, accumulates in cerebral areas where the blood-brain barrier is damaged. This quality makes it an ideal dye for the intraoperative visualization of high-grade gliomas (HGGs). The authors report their experience with a new fluorescein-guided technique for the resection of HGGs using a dedicated filter on the surgical microscope. Methods The authors initiated a prospective Phase II trial (FLUOGLIO) in September 2011 with the objective of evaluating the safety of fluorescein-guided surgery for HGGs and obtaining preliminary evidence regarding its efficacy for this purpose. To be eligible for participation in the study, a patient had to have suspected HGG amenable to complete resection of the contrast-enhancing area. The present report is based on the analysis of the short- and long-term results in 20 consecutive patients with HGGs (age range 45–74 years), enrolled in the study since September 2011. In all cases fluorescein (5–10 mg/kg) was injected intravenously after intubation. Tumor resection was performed with microsurgical technique and fluorescence visualization by means of BLUE 400 or YELLOW 560 filters on a Pentero microscope. Results The median preoperative tumor volume was 30.3 cm3 (range 2.4–87.8 cm3). There were no adverse reactions related to fluorescein administration. Complete removal of contrast-enhanced tumor was achieved in 80% of the patients. The median duration of follow-up was 10 months. The 6-months progression-free survival rate was 71.4% and the median survival was 11 months. Conclusions Analysis of these 20 cases suggested that fluorescein-guided technique with a dedicated filter on the surgical microscope is safe and allows a high rate of complete resection of contrast-enhanced tumor as determined on early postoperative MRI. Clinical trial registration no.: 2011-002527-18 (EudraCT).

Object The aim of this study was to review the indications for and results of deep brain stimulation (DBS) of the posterior hypothalamus (pHyp) in the treatment of drug-refractory and severe painful syndromes of the face, disruptive and aggressive behavior associated with epilepsy, and below-average intelligence. The preoperative clinical picture, functional imaging studies, and overall clinical results in the literature are discussed. Methods All patients underwent stereotactic implantation of deep-brain electrodes within the pHyp. Data from several authors have been collected and reported for each clinical entity, as have clinical results, adverse events, and neurophysiological characteristics of the pHyp. Results The percentage of patients with chronic cluster headache who responded to DBS was 50% in the overall reported series. The response rate was 100% for short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing and for chronic paroxysmal hemicrania, although only 2 patients and 1 patient, respectively, have been described as having these conditions. None of the 4 patients suffering from refractory neuropathic trigeminal pain benefited from the procedure (0% response rate), whereas all 5 patients (100%) affected with refractory trigeminal neuralgia (TN) due to multiple sclerosis (MS) and undergoing pHyp DBS experienced a significant decrease in pain attacks within the first branch of cranial nerve V. Six (75%) of 8 patients presenting with aggressive behavior and mental retardation benefited from pHyp stimulation; 6 patients were part of the authors' series and 2 were reported in the literature. Conclusions In carefully selected patients, DBS of the pHyp can be considered an effective procedure for the treatment of refractory trigeminal autonomic cephalalgias, aggressive behavior, and MS-related TN in the first trigeminal branch. Only larger and prospective studies along with multidisciplinary approaches (including, by necessity, neuroimaging studies) can lead us to better patient selection that would reduce the rate of nonresponders.

Neuroimaging studies in cluster headache (CH) patients have increased understanding of attack-associated events and provided clues to the pathophysiology of the condition. They have also suggested stimulation of the ipsilateral posterior inferior hypothalamus as a treatment for chronic intractable CH. After 8 years of experience, stimulation has proved successful in controlling the pain attacks in almost 60% of chronic CH patients implanted at various centres. Although hypothalamic implant is not without risks, it has generally been performed safely. Implantation affords an opportunity to perform microrecordings of individual posterior hypothalamic neurons. These studies are at an early stage, but suggest the possibility of identifying precisely the target site by its electrophysiological characteristics. Autonomic studies of patients undergoing posterior hypothalamic stimulation provide further evidence that long-term stimulation is safe, revealing that it can cause altered modulation of the mechanisms of orthostatic adaptation without affecting the baroreflex, cardiorespiratory interactions or efferent sympathetic and vagal functions. Chronically stimulated patients have an increased threshold for cold pain at the site of the first trigeminal branch ipsilateral to the stimulated side; when the stimulator is switched off, changes in sensory and pain thresholds do not occur immediately, suggesting that long-term stimulation is required to induce sensory and nociceptive changes. Posterior inferior hypothalamic stimulation is now established as a treatment for many chronic CH patients. The technique is shedding further light on the pathophysiology of the disease, and is also providing clues to functioning of the hypothalamus itself.

Fluorescein is widely used as a fluorescent tracer for many applications. Its capacity to accumulate in cerebral areas where there has been blood-brain barrier damage makes it particularly suitable as a dye for the intraoperative visualization of malignant gliomas (MGs). In this report, we describe the results of a comprehensive review on the use of fluorescein in the surgical treatment of MGs. A comprehensive literature search and review for English-written articles concerning the use of fluorescein in the resection of MGs has been conducted. The search was executed through a PubMed literature search using the following keywords: malignant gliomas, glioblastomas, high-grade gliomas, YELLOW 560, total removal, dedicated filter, neurosurgery, brain tumors, intracranial tumors, and confocal microscopy. The literature search resulted in the retrieval of 412 evidence-based articles. Of these, 17 were found to be strictly related to the resection of MG with the aid of fluorescein. In addition to these 17, we have included 2 articles derived from a personal database of the corresponding author (FA). The analysis of the articles reviewed revealed three major applications of fluorescein during surgery for MGs that was documented: Fluorescein-guided resection of MGs with white-light illumination, fluorescein-guided resection of MGs with a surgical microscope equipped with a dedicated filter for fluorescein, and confocal microscopy for intraoperative histopathological analysis on MGs. The systemic review conducted on the use of fluorescein in MGs explored the applications and the different modalities in which fluorescein has been used. The data we have gathered indicates that fluorescein-guided surgery is a safe, effective, and convenient technique to achieve a high rate of total removal in MGs. Further prospective comparative trials, however, are still necessary to prove the impact of fluorescein-guided surgery on both progression-free survival and overall survival.

Resting state fMRI (rs-fMRI) has recently been considered as a possible complement or alternative to task-based fMRI (tb-fMRI) for presurgical mapping. However, evidence of its usefulness remains scant, because existing studies have investigated relatively small samples and focused primarily on qualitative evaluation. The aim of this study is to investigate the clinical usefulness of rs-fMRI in the context of presurgical mapping of motor functions, and in particular to determine the degree of correspondence with tb-fMRI which, while not a gold-standard, is commonly used in preoperative setting. A group of 13 patients with lesions close to the sensorimotor cortex underwent rs-fMRI and tb-fMRI to localize the hand, foot and mouth motor areas. We assessed quantitatively the degree of correspondence between multiple rs-fMRI analyses (independent-component and seed-based analyses) and tb-fMRI, with reference to sensitivity and specificity of rs-fMRI with respect to tb-fMRI, and centre-of-mass distances. Agreement with electro-cortical stimulation (ECS) was also investigated, and a traditional map thresholding approach based on agreement between two experienced operators was compared to an automatic threshold determination method. Rs-fMRI can localize the sensorimotor cortex successfully, providing anatomical specificity for hand, foot and mouth motor subregions, in particular with seed-based analyses. Agreement with tb-fMRI was only partial and rs-fMRI tended to provide larger patterns of correlated activity. With respect to the ECS data available, rs-fMRI and tb-fMRI performed comparably, even though the shortest distance to stimulation points was observed for the latter. Notably, the results of both were on the whole robust to thresholding procedure. Localization performed by rs-fMRI is not equivalent to tb-fMRI, hence rs-fMRI cannot be considered as an outright replacement for tb-fMRI. Nevertheless, since there is significant agreement between the two techniques, rs-fMRI can be considered with caution as a potential alternative to tb-fMRI when patients are unable to perform the task.