Temozolomide cytoreductive treatment in a giant cabergoline-resistant prolactin-secreting pituitary neuroendocrine tumor.

Dopamine agonists (DAs, especially cabergoline) are recommended as first-line treatment in patients with prolactin-secreting pituitary adenomas, to reduce hormone secretion and tumor size. Pituitary surgery, suggested in nonresponsive patients, cannot achieve a gross total resection or is not feasible in some cases. Temozolomide (TMZ) has been proposed in patients with aggressive pituitary neuroendocrine tumors (PitNETs) who do not respond to conventional treatments. We present a 47-year-old man with a giant (70×51×64 mm) prolactin-secreting PitNET. Cabergoline treatment (at first 1.5 mg/week, and then increased to 3.5 mg/week after 3 months) achieved prolactin suppression; however, magnetic resonance revealed a stable mass. After explanation of surgical complications, the patient rejected the procedure. Therefore, a primary neoadjuvant cytoreductive TMZ treatment was discussed during a meeting of the Pituitary Multidisciplinary Team, and added to cabergoline. After 13 cycles of TMZ (1 year of treatment), we observed dramatic reduction of the PitNET (from 18 cm of adenoma to 6 cm of necrotic tissue). MRI performed 4, 12, and 18 months after TMZ discontinuation revealed a stable residual PitNET, and 1.5 mg/week of cabergoline has been continued until today. Recently, the criteria for developing Pituitary Tumors Centers of Excellence have been proposed, indicating that a multidisciplinary team is the best care for patients. Surgery, rejected by the patient, could only achieve a partial resection; therefore, we decided to combine TMZ and cabergoline. An early initiation of TMZ could be considered in selected cases, especially when surgery could be only partially effective.

Early recognition of aggressive pituitary adenomas: a single-centre experience.

BACKGROUND: Pituitary adenomas are usually considered benign tumours, although some of them can exhibit an aggressive behaviour. Patients with clinically aggressive pituitary adenomas are frequently diagnosed with larger masses, and may present an earlier recurrence (or persistence) after surgery. Our aim was to characterise the clinical, histopathological and radiological features of patients with aggressive pituitary adenoma, in order to correlate their clinical behaviour with the response to treatment plan. METHOD: We considered an aggressive pituitary adenoma on the basis of radiological features (size, local invasion), pathological reports (atypical adenoma: MIB-1 >3%, p53 immunoreactivity, increased mitotic activity) and clinical aspects (response to surgery, radiotherapy and medical treatment). RESULTS: Among our cohort of 582 patients, we considered 102 subjects with aggressive pituitary adenomas (18%, 56 male and 46 female): 14 adrenocorticotrophic hormone (ACTH)-secreting, 18 growth hormone (GH)-secreting, 23 prolactin (PRL)-secreting and 47 non-secreting, with a median follow-up of 5 years. In the whole cohort, 75% of patients with aggressive pituitary adenomas presented invasion of surrounding structure, especially GH-secreting, PRL-secreting and non-secreting. Besides invasion, their remission rate after surgery, radiotherapy or medical treatment was similar, irrespective of hormonal secretion. Surgery was the most performed treatment (overall remission rate of 24%), especially in those patients with ACTH- or GH-secreting adenoma, and 22% of patients were submitted to radiotherapy, with a remission rate of 45% after a median of 3 years. Two consecutive years of medical treatment, in patients with secreting pituitary adenoma, achieved disease control in 41% of them. Considering pathological reports, 24% of cases were defined as atypical adenomas; radiological characteristics, responses to medical treatment and remission rates were similar among patients with typical and atypical adenoma. CONCLUSIONS: We proposed a new and comprehensive definition of aggressive pituitary adenoma, based upon radiological, clinical and pathological features. In a selected cohort of patients, radiological invasion resulted in the most common marker to describe the aggressive behaviour of pituitary adenoma. Surgery, radiotherapy and medical treatment (the latter only in secreting adenoma) achieved disease control in half of the patients with aggressive adenoma, especially surgery in those with ACTH-oma and medical treatment in those with GH- and PRL-secreting adenoma. Nevertheless, radiological, clinical or atypical features did not affect the outcome.

Cardiovascular autonomic dysfunction in patients with idiopathic diabetes insipidus.

INTRODUCTION: Central diabetes insipidus (DI) is a rare disease characterized by the excretion of excessive volumes of dilute urine due to reduced levels of the antidiuretic hormone arginine vasopressin (AVP), caused by an acquired or genetic defect in the neurohypophysis. The aim of this study was to identify any autonomic dysfunction (AD) in patients with DI as a possible cofactor responsible for their reportedly higher mortality. METHODS: The study involved 12 patients (6 females) with central idiopathic DI and a well-controlled electrolyte balance, and 12 controls matched for age, sex and cardiovascular risk factors, who were assessed using the tilt, lying-to-standing, hand grip, deep breath, Valsalva maneuver and Stroop tests. RESULTS: The tilt test showed a significantly more pronounced decrease in both systolic (- 20.67 ± 18 vs. - 1.92 ± 6.99 mmHg, p = 0.0009) and diastolic blood pressure (- 10.5 ± 14.29 vs. - 1.5 ± 5 mmHg, p = 0.012) in patients than in controls. Three patients with DI had to suspend the test due to the onset of syncope. The lying-to-standing test also revealed a marked reduction in blood pressure in patients with DI (1.05 ± 0.13 vs. 1.53 ± 0.14, p = 0.0001). Similar results emerged for the Valsalva maneuver (Valsalva ratio, 1.24 ± 0.19 vs. 1.79 ± 0.11, p < 0.0001) and deep breath test (1.08 ± 0.11 vs. 1.33 ± 0.08, p < 0.0001). CONCLUSIONS: All the principal autonomic tests performed in the study were concordant in indicating that patients with central DI have an impaired autonomic nervous system function despite a normal hydroelectrolytic balance under desmopressin therapy. This impairment may reflect damage to the autonomic system per se and/or the absence of any vasoactive effect of AVP on vascular smooth muscle. In our opinion, patients with central DI should be educated on how to prevent orthostatic hypotension, and pharmacological treatment should be considered for patients with a more marked impairment.

Hippocampal Gray Volumes Increase in Treatment-Resistant Depression Responding to Vagus Nerve Stimulation.

BACKGROUND: Changes in hippocampal gray matter volumes are proposed to be involved in pathogenesis, course, and treatment response of major depressive disorder. Converging evidence suggests that reduced neurogenesis may occur in treatment-resistant depression (TRD). Vagus nerve stimulation (VNS) is a well-defined, long-term brain stimulation treatment for TRD. However, its in vivo positive effect on hippocampal modulation as mechanism of action has never been investigated before in clinical studies. In this study, we intended to explore hippocampal volumetric changes and clinical antidepressant responses in patients with TRD after 6 and 12 months of treatment with VNS. METHODS: The TRD outpatients were evaluated for VNS implantation. Right and left hippocampal volumes in 6 TRD patients, who met the criteria for VNS treatment, were measured at baseline before the implantation and after 6 and 12 months. The patients were assessed using Beck Depression Inventory and Hamilton Depression Rating Scale at baseline and at follow-up visits. RESULTS: There was a statistically significant and progressive increase in right and left hippocampal volumes during the follow up (P < 0.05). Furthermore, patients showed a significant improvement on Hamilton Depression Rating Scale and Beck Depression Inventory scores (P < 0.05). CONCLUSIONS: Our data suggest a VNS modulatory effect on hippocampal plasticity as measured by hippocampal gray volume increase in TRD patients. These preliminary findings indicate the fundamental role of hippocampal remodeling as a marker of response to VNS in TRD.

Outcome of patients affected by newly diagnosed glioblastoma undergoing surgery assisted by 5-aminolevulinic acid guided resection followed by BCNU wafers implantation: a 3-year follow-up.

The purpose of the study was to evaluate the clinical outcome of the association of BCNU wafers implantation and 5-aminolevulinic acid (5-ALA) fluorescence in the treatment of patients with newly diagnosed glioblastoma (ndGBM). Clinical and surgical data from patients who underwent 5-ALA surgery followed by BCNU wafers implantation were retrospectively evaluated (20 patients, Group I) and compared with data of patients undergoing surgery with BCNU wafers alone (42 patients, Group II) and 5-ALA alone (59 patients, Group III). Patients undergoing 5-ALA assisted resection followed by BCNU wafers implantation (Group I) resulted long survivors (>3 years) in 15 % of cases and showed a median PFS and MS of 11 and 22 months, respectively. Patients treated with BCNU wafers presented a significantly higher survival when tumor was removed with the assistance of 5-ALA (22 months with vs 18 months without 5-ALA, p < 0.0001); these data could be partially explained by the significantly higher CRET achieved in patients operated with 5-ALA assistance (80 % with vs 47 %% without 5-ALA). Moreover, patients of Group I showed a significant increased survival compared with Group III (5-ALA without BCNU) (22 months with vs 21 months without BCNU wafers, p = 0.0025) even with a comparable CRET (80 % vs 76 %, respectively). The occurrence of adverse events related to wafers did not significantly increase with 5-ALA (20 % with and 19 % without 5-ALA) and did not impact in survival outcome. In conclusion, our experience shows that on selected ndGBM patients 5-ALA technology and BCNU wafers implantation show a synergic action on patients' outcome without increasing adverse events occurrence.

Second-line tests in the differential diagnosis of ACTH-dependent Cushing's syndrome.

INTRODUCTION: Diagnosing Cushing's syndrome (CS) can be a challenge, especially in ACTH-dependent CS, when it comes to detecting the origin of ACTH secretion. MATERIALS AND METHODS: Retrospective data were collected on 170 patients with ACTH-dependent CS (149 CD, 21 EAS) referring to two endocrinology units, focusing on three non-invasive tests: dexamethasone 8 mg overnight challenge (HDDST); corticotrophin-releasing hormone (CRH) assay and the desmopressin (DDAVP) test. RESULTS: Patients with EAS were slightly older and had higher ACTH, serum and urinary cortisol levels than patients with CD (p < 0.01). CD patients had a stronger ACTH and cortisol response after CRH injection (p < 0.0001), and a more pronounced reduction in cortisol levels after HDDST (p < 0.0001). A threshold percentage ACTH increase after CRH stimulation of 72.4 % was able to identify CD with a sensitivity (SE) of 76 % (95 % CI 68-83) and a specificity (SP) of 100 % (95 % CI 83-100). As for HDDST, a cortisol suppression >52.7 % below the basal level suggested a pituitary origin with a SE of 88 % (95 % CI 81-93) and a SP of 90 % (95 % CI 68-99). There were no cases of EAS with positive responses to both these tests. Increases in ACTH and cortisol levels after the DDAVP test were also higher in CD than in EAS (p < 0.01), though the SE and SP were lower. CONCLUSIONS: Patients with CD showed a stronger response to HDDST and CRH, and the adopted cut-offs showed a good SE and SP in discriminating them from patients with EAS. Concordant tests indicated CD when positive, whereas no response to either test was highly suggestive of EAS. The DDAVP test was of limited utility in the diagnostic phase. In conclusion, the choice of tests may play an important part in the differential diagnosis of ACTH-dependent CS.

Zero in the brain: A voxel-based lesion-symptom mapping study in right hemisphere damaged patients.

Transcoding numerals containing zero is more problematic than transcoding numbers formed by non-zero digits. However, it is currently unknown whether this is due to zeros requiring brain areas other than those traditionally associated with number representation. Here we hypothesize that transcoding zeros entails visuo-spatial and integrative processes typically associated with the right hemisphere. The investigation involved 22 right-brain-damaged patients and 20 healthy controls who completed tests of reading and writing Arabic numbers. As expected, the most significant deficit among patients involved a failure to cope with zeros. Moreover, a voxel-based lesion-symptom mapping (VLSM) analysis showed that the most common zero-errors were maximally associated to the right insula which was previously related to sensorimotor integration, attention, and response selection, yet for the first time linked to transcoding processes. Error categories involving other digits corresponded to the so-called Neglect errors, which however, constituted only about 10% of the total reading and 3% of the writing mistakes made by the patients. We argue that damage to the right hemisphere impairs the mechanism of parsing, and the ability to set-up empty-slot structures required for processing zeros in complex numbers; moreover, we suggest that the brain areas located in proximity to the right insula play a role in the integration of the information resulting from the temporary application of transcoding procedures.

MRI-detectable cortical lesions in the cerebellum and their clinical relevance in multiple sclerosis.

BACKGROUND: The demonstration of cortical lesions (CL) in the cerebellum by magnetic resonance imaging (MRI) is hampered by technical and anatomical constraints. OBJECTIVE: To investigate the occurrence of cerebellar CL and their correlation with cerebellar-related disability by combining Double Inversion Recovery (DIR) and Phase Sensitive Inversion Recovery (PSIR) MRI images in multiple sclerosis (MS) patients. MATERIAL AND METHODS: 40 MS patients (10 CIS/eRRMS, 24 RRMS, 6 SPMS), having a wide range of disability and disease duration, were enrolled. DIR and PSIR images were obtained with a 3T-MRI. RESULTS: Cerebellar white matter lesions (WML) and/or CL were observed in 33/40 patients (82.5%) among which 14/40 had only CL. CL were demonstrated in 26/40 patients by DIR and in 31/40 by PSIR, and their number increased from CIS/eRRMS to SPMS. PSIR disclosed a significantly higher number of CL compared to DIR (RRMS: p=0.0008; SPMS: p=0.002). CL number correlates with the cerebellar Expanded Disability Status Score (EDSS) score (r=0.72, p<0.0001). No correlation was observed between supra-tentorial and cerebellar CL. CONCLUSIONS: CL are detected by PSIR in the cerebellum of the majority of MS patients, are more than WML, increase with disease progression and strongly correlate with the cerebellar EDSS. Thus, the observation of CL in the cerebellum of MS at clinical onset might be useful for prognostic and therapeutic aims.

Surgery on motor area metastasis.

The role of surgery on central area metastasis remains unclear, and outcome data are still controversial. The aim of our study is to analyze the predictive value of clinical and surgical data on motor and functional outcome of patients, taking into account new emerging data on boundary irregularity of brain metastasis. We retrospectively analyzed 47 consecutive patients who underwent surgery assisted by neurophysiologic monitoring for a solitary metastasis in central area between 2010 and 2013. Inclusion criteria were as follows: good functional status (Karnofsky Performance Status (KPS) ≥70), controlled systemic disease, and absence of extra-cranial dissemination. At 1-month follow up, motor and functional outcomes were compared with preoperative clinical status, response to corticosteroids, extent of tumor resection, boundary irregularity, and size of tumor. Gross total resection was achieved in 93.6% of cases. In preoperative symptomatic patients, motor outcome (according to Medical Research Council grading scale) improved in 55.5% and worsened in 16.7%, while functional outcome (according to KPS score) improved in 50% and worsened in 14.2% of cases. No worsening occurred in preoperative asymptomatic patients. Motor outcome resulted to be not correlated with preoperative deficits, tumor volume, or preoperative response to corticosteroid treatment. Remarkably, motor outcome and extent of surgical resection appeared strongly correlated with tumor boundary irregularity (p < 0.05). Surgery with neurophysiologic monitoring on motor area metastasis can improve functional and motor condition in selected patients. Tumor volume does not represent a limit in surgery. The high correlation between clinical outcome, resection rate, and tumor boundary irregularity strengthens a new belief on the infiltrative growing pattern of brain metastasis. Motor function was evaluated according to Medical Research Council grading scale (Ott et al. 2014) while functional status was assessed according to KPS score.

Cortical relapses in multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a white and grey matter disease of the central nervous system (CNS). It is recognized that cortical damage (i.e. focal lesions and atrophy) plays a role in determining the accumulation of physical and cognitive disability that is observed in patients with progressive MS. To date, an association of cortical lesions with clinical relapses has not been described. RESULTS: We report clinical and magnetic resonance imaging (MRI) findings of five relapsing-remitting MS (RRMS) patients who had clinical relapses characterized by the acute appearance of cortical symptoms, due to the development of large, snake-like, cortical inflammatory lesions. Symptoms were: acute Wernicke's aphasia mimicking stroke; agraphia with acalculia, not associated to a motor deficit nor linguistic disturbance; hyposthenia of the left arm, followed by muscle twitching of the hand, spreading to arm and face; acute onset of left lower limb paroxysmal hypertonia; and temporal lobe status epilepticus, with psychotic symptoms. CONCLUSIONS: Cortical relapses may occur in MS. MRI examination in MS should include sequences, such as double inversion recovery (DIR) or phase sensitive inversion recovery (PSIR), that are aimed at visualizing cortical lesions, especially in the presence of symptoms of cortical dysfunction. Our observation further stresses and extends the clinical relevance of cortical pathology in MS.

Neuroimaging Five Hundred Years Later

The rapid technological progress of these last decades has brought refined instruments to neuroradiologists and consequently to anatomists, physiologists, neuroscientists. A short outline is given on recent advancements in the field. Looking at these wonderful images we must not forget the works of our predecessors, to whom we owe an inextinguishable gratitude.

Intraparenchymal ventricular diverticula in chronic obstructive hydrocephalus: prevalence, imaging features and evolution.

BACKGROUND: Intraparenchymal cavities communicating with the ventricles may appear in patients with chronic obstructive hydrocephalus despite no identifiable surgerical, vascular or traumatic causes. The rate, features, pathogenesis, evolution and clinical impact of intraparenchymal diverticula have not been outlined, yet. METHODS: Brain MRIs of 130 patients (mean age: 11.3 years; age range: 0-67; 60 females) with chronic obstructive hydrocephalus were analyzed. The pathogenesis, neurosurgical treatment, ventricle size, signs of transependymal reabsorption and septum pellucidum integrity of the hydrocephalus were recorded. Subarachnoid outpouching of the ventricles, post-hemorrhagic parenchymal cavities, paths of ventricular shunting and cavities not communicating with the ventricles were excluded. Of patients with intraparenchymal diverticula, all previous available CT and MRI scans were evaluated. RESULTS: Eight patients (6.2 %, mean age: 18.7 years; age range: 2-42) harbored 11 intraparenchymal diverticula sprouting from the temporal (6), occipital (3) or frontal (2) horns of the lateral ventricles. Intraparenchymal diverticula were more frequent in males (p = 0.04) and older patients (18.7 ± 12.7 vs 11.3 ± 9.8 years, p = 0.04). Their presence or evolution (mean neuroradiological follow-up 3.6 years; range: 0-8) showed a trend of association with hydrocephalus severity (bifrontal index) and did not correlate with the surgical treatment. In three patients the diverticula progressed during follow-up. One patient presented with hemiparesis consistent with the intraparenchymal lesion and improved after ventricular shunting. A DTI study revealed that the cortico-spinal tract was partly included in the septum between the ventricle and the intraparenchymal diverticulum. CONCLUSIONS: Clinicians dealing with chronic severe obstructive hydrocephalus should be aware of ventricular intraparenchymal diverticulation. Studies aiming at clarifying their pathogenesis and proper management are warranted.

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.

The Parallel Analysis of Phase Sensitive Inversion Recovery (PSIR) and Double Inversion Recovery (DIR) Images Significantly Improves the Detection of Cortical Lesions in Multiple Sclerosis (MS) since Clinical Onset.

BACKGROUND: Double inversion recovery (DIR) detects only a minority (<20%) of cortical lesions (CL) in multiple sclerosis (MS). Phase-sensitive inversion recovery (PSIR) was suggested to be substantially superior to DIR in the detection of cortical lesions (CL). These two sequences might be complementary. OBJECTIVES: To analyze CL frequency and type in MS patients having different disease duration and disability, including patients at clinical onset, and to discern more correctly the artifacts, by combining DIR and PSIR images. PATIENTS AND METHODS: 40 patients were enrolled in the study: 10 clinically isolated syndrome/early relapsing remitting MS (CIS/eRRMS), 24 relapsing remitting MS (RRMS), 6 secondary progressive MS (SPMS). DIR and PSIR images were jointly used to classify lesions as purely intracortical (IC), leukocortical (LC) and juxtacortical (JC). RESULTS: PSIR disclosed CL in 100% of the patients and was capable of identifying more than four times lesions (455.5%, p<0.00001), especially IC (mean numbers: 36.5 in CIS/eRRMS, 45.0 in RRMS and 52.3 in SPMS) and LC (mean numbers: 10.9 in CIS/eRRMS, 20.1 in RRMS and 25.3 in SPMS), compared to DIR (p<0.00001). CL number was significantly higher in SPMS compared to RRMS (p<0.0001). Artifacts were more accurately identified by comparing the two sequences. CONCLUSIONS: Our study confirms the higher ability of PSIR in disclosing and classifying CL. The presence of CL in all CIS patients further points out the relevance of cortical pathology in MS. Whether the parallel analysis of DIR and PSIR images may be useful for diagnostic purposes, especially when a diagnosis of MS is suspected but not confirmed by routine MRI, needs to be evaluated in larger patient series. The analysis of the cortex by DIR and PSIR may also allow a better stratification of the patients for prognostic and counseling purposes, as well as for their inclusion in clinical studies.

5-Aminolevulinic acid fluorescence in high grade glioma surgery: surgical outcome, intraoperative findings, and fluorescence patterns.

BACKGROUND: 5-Aminolevulinic acid (5-ALA) fluorescence is a validated technique for resection of high grade gliomas (HGG); the aim of this study was to evaluate the surgical outcome and the intraoperative findings in a consecutive series of patients. METHODS: Clinical and surgical data from patients affected by HGG who underwent surgery guided by 5-ALA fluorescence at our Department between June 2011 and February 2014 were retrospectively evaluated. Surgical outcome was evaluated by assessing the resection rate as gross total resection (GTR) > 98% and GTR > 90%. We finally stratified data for recurrent surgery, tumor location, tumor size, and tumor grade (IV versus III grade sec. WHO). RESULTS: 94 patients were finally enrolled. Overall GTR > 98% and GTR > 90% was achieved in 93% and 100% of patients. Extent of resection (GTR > 98%) was dependent on tumor location, tumor grade (P < 0.05), and tumor size (P < 0.05). In 43% of patients the boundaries of fluorescent tissue exceeded those of tumoral tissue detected by neuronavigation, more frequently in larger (57%) (P < 0.01) and recurrent (60%) tumors. CONCLUSIONS: 5-ALA fluorescence in HGG surgery enables a GTR in 100% of cases even if selection of patients remains a main bias. Recurrent surgery, and location, size, and tumor grade can predict both the surgical outcome and the intraoperative findings.

Application of indocyanine green video angiography in parasagittal meningioma surgery.

OBJECT: There are no doubts about the role that indocyanine green video angiography (ICGVA) can play in current vascular neurosurgery. Conversely, in brain tumor surgery, and particularly in meningioma surgery, this role is still unclear. Vein management is pivotal for approaching parasagittal meningiomas, because venous preservation is strictly connected to both extent of resection and clinical outcome. The authors present the technical traits and the postoperative outcome of the application of ICGVA in patients undergoing parasagittal meningioma surgery. METHODS: The authors retrospectively collected demographic, radiological, intraoperative, and follow-up data in 43 patients with parasagittal meningiomas who underwent surgery with the assistance of ICGVA at Padua Neurosurgical Department between October 2010 and July 2013. Intraoperative ICGVA findings at different stages (before dural opening, after dural opening, during resection, after resection) were reviewed. Additional data on functional monitoring, temporary venous clipping, and flow measurements were also recorded. The overall postoperative outcome was evaluated by assessing both the extent of resection and the clinical outcome data. RESULTS: The ICGVA studies were performed 125 times in 43 patients, providing helpful data for vein management and tumor resection in all stages of surgery. In 16% of meningiomas completely occluding the superior sagittal sinus, the ICGVA data differed from radiological findings and changed the surgical approach. In 20% of cases the intraoperative ICGVA findings directly guided the surgical strategy: venous sacrifice was necessary in 7 cases, without postoperative consequences; temporary clipping with neurophysiological monitoring proved to be predictive of safe venous sacrifice. In 7% of cases the ICGVA data needed to be supplemented with flow measurements. Simpson Grade I-II and Grade III resections were achieved in 86% and 14% of cases, respectively, with a 4.6% rate of overall morbidity. CONCLUSIONS: This study shows that ICGVA can assist the different stages of parasagittal meningiomas surgery, guiding the vein management and tumor resection strategies with a favorable final clinical outcome. However, in the authors' experience the use of other complementary tools was mandatory in selected cases to preserve functional areas. Further studies are needed to confirm that the application of ICGVA in parasagittal meningioma surgery may improve the morbidity rate, as reported in this study.

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.

Subintimal angioplasty of infrapopliteal artery occlusions in the treatment of critical limb ischaemia. Short-term results.

AIM: To evaluate the feasibility and efficacy of subintimal infrapopliteal angioplasty (SIA) as a method for recanalization of occluded tibial arteries in the treatment of critical limb ischaemia (CLI). MATERIALS AND METHODS: Between January 2002 and September 2003, 20 patients with CLI were submitted to SIA; of these, 16 had diabetes mellitus. All patients had foot ulceration or gangrene and ten had rest pain. All patients were treated with SIA of one or more vessels of the popliteal district. Overall, thirty-four arteries of the infrapopliteal district underwent revascularization; in 9 cases, SIA of superficial femoral artery occlusions was associated. Technical success was evaluated on angiography at the end of the procedure: revascularization of at least one of the 3 leg vessels with re-establishment of arterial flow to the foot was regarded as a technical success. Pain relief (when pain was present) and healing of foot ulceration, without above-the-ankle major amputation (limb salvage), were defined as clinically successful. During the follow-up (mean: 9 months; range: 6-21 months) all patients were checked 6 months after the procedure by clinical examination and colour-Doppler ultrasound. RESULTS: The technical success rate of SIA in the revascularization of the infrapopliteal vessels was 85%. In the 17 technically successful cases, pain had entirely resolved in 9/10 cases and trophic lesions of the foot healed in 14/17 cases. In this group, 9 patients underwent minor amputation; 2 underwent major above-the-ankle amputation; one underwent to surgery 20 days after the SIA and required a femoro-tibial by-pass. In the 3 cases of technical failure (15%), revascularization of the entire occluded tract could not be achieved. Of these, one patient subsequently underwent major amputation. Nine months after SIA, the cumulative limb salvage rate was 85% (17/20 clinically successful cases) and the survival rate was 90%. Colour-Doppler US at 6 months showed 70% primary patency. No major complication occurred during the procedure. Five minor complications in four patients were managed endovascularly or healed spontaneously. CONCLUSIONS: SIA is a feasible and effective technique for foot revascularization in patients with CLI. Long occlusions or diffusely calcified arteries are suitable indications. Technical failure does not preclude conventional surgery. In patients treated with SIA, the risk of major amputation is low and mortality rate is nil. Minor complications can be managed using endovascular techniques.