Evaluate the safety and efficacy of dura sealant patch in reducing cerebrospinal fluid leakage following elective cranial surgery (ENCASE II): study protocol for a randomized, two-arm, multicenter trial.

BACKGROUND: Cerebrospinal fluid (CSF) leakage is a frequent and challenging complication in neurosurgery, especially in the posterior fossa, with a prevalence of 8%. It is associated with substantial morbidity and increased healthcare costs. A novel dural sealant patch (LIQOSEAL) was developed for watertight dural closure. The objective of this study is to clinically assess the safety and effectiveness of LIQOSEAL as a means of reducing intra- as well as postoperative CSF leakage in patients undergoing elective posterior fossa intradural surgery with a dural closure procedure compared to the best currently available dural sealants. METHODS: We will conduct a two-arm, randomized controlled, multicenter study with a 90-day follow-up. A total of 228 patients will be enrolled in 19 sites, of which 114 will receive LIQOSEAL and 114 an FDA-approved PEG sealant. The composite primary endpoint is defined as intraoperative CSF leakage at PEEP 20 cm H2O, percutaneous CSF leakage within 90 days of, wound infection within 90 days of or pseudomeningocele of more than 20cc on MRI or requiring intervention. We hypothesize that the primary endpoint will not be reached by more than 10 patients (9%) in the investigational arm, which will demonstrate non-inferiority of LIQOSEAL compared to control. DISCUSSION: This trial will evaluate whether LIQOSEAL is non-inferior to control as a means of reducing CSF leakage and safety TRIAL REGISTRATION: ClinicalTrials.gov NCT04086550 . Registered on 11 September 2019.

First but not second postoperative day growth hormone assessments as early predictive tests for long-term acromegaly persistence.

PURPOSE: Postoperative assessment of acromegaly activity is typically performed at least 3 months after neurosurgery (NS). Few studies have evaluated the use of early postoperative growth hormone (GH) levels as a test to predict short- and long-term remission of acromegaly. Our objective was to evaluate the diagnostic performance of serum random GH on a postoperative day one (D1-rGH) and two (D2-rGH), particularly in predicting long-term disease persistence. MATERIALS AND METHODS: Forty-one subjects with acromegaly who were undergoing NS were enrolled (mean age ± SD 47.4 ± 13.1 years at diagnosis; women 54%; macroadenomas 71%). The final assessment of disease activity was performed one year after NS. ROC curves were used to evaluate the diagnostic performance of D1-rGH and D2-rGH. RESULTS: After a 1-year follow-up, the overall remission rate was 55%. ROC analysis identified an optimal D1-rGH cut-off value of 2.1 ng/mL for diagnosing long-term disease persistence (55.6% SE; 90.9% SP). The cut-off point became 2.5 ng/mL after maximizing specificity for disease persistence (yielding a 100% positive predictive value) and 0.3 ng/mL after maximizing sensitivity for disease remission. The optimal D2-rGH cut-off value was 0.6 ng/mL (81.8% SE; 50% SP); the cut-off point became 2.9 ng/mL after maximizing specificity and 0.1 ng/mL after maximizing sensitivity, with no clinical utility. CONCLUSIONS: D1-rGH could be a highly specific test for the early diagnosis of long-term acromegaly persistence, which is predicted by a value > 2.5 ng/mL with a great degree of certainty. The diagnostic performance of D2-rGH was insufficient. Further research is required to validate these preliminary results prior to modifying the postoperative management of acromegaly.

Neurological outcomes after surgery for spinal metastases in symptomatic patients: Does the type of decompression play a role? A comparison between different strategies in a 10-year experience.

INTRODUCTION: The impact of neurological deficits plays a role of inestimable importance in patients with a neoplastic disease. The role of surgery for the management of symptomatic spinal cord compression (SSCC) cannot be overemphasized, as surgery represents often the first and paramount step in patients presenting with motor deficits. The traditional paradigm of simple bilateral laminectomy for the treatment of spinal cord compression has been reviewed. The need to achieve a proper circumferential decompression of the spinal sac has been progressively highlighted in combination with the development of the more comprehensive and multidisciplinary concept of separation surgery. OBJECTIVE: The aim of this paper is to analyze different strategies of decompression, while evaluating whether circumferential/anterior decompression is able to guarantee a better control and restoration of neurological functions in patients with motor impairment, if compared to traditional posterior decompression. MATERIALS AND METHODS: This is a retrospective observational study investigating symptomatic patients that underwent surgical treatment for spinal metastases at author's Institutions from January 2010 to June 2019. Data recorded concerned patient demographics, tumor histology, peri-operative and follow-up neurological status (ASIA), ambulation ability, stability (SINS), grade (ESCC) and source of epidural compression and type of decompression (anterior/anterior-lateral (AD); posterior/posterior-lateral (PD/PDL); circumferential (CD)). RESULTS: A total number of 84 patients was included. AD/CD patients showed higher chance of neurological improvement and reduced rates of worsening compared to PD/PLD group (94.1%/100% vs 60.4%; 11.8% vs 45.8% respectively). Univariate logistic regression identified immediate post-operative improvement to be a significative protective factor for worsening at last follow-up. Stratifying patients for site of compression and considering anterior and circumferential groups, immediate post-operative neurological improvement, was mostly associated with AD and CD (p 0.011 and 0.025 respectively). Walking at last follow up was influenced by post-operative maintenance of ambulation (p 0.001). CONCLUSION: The necessity to remove the epidural metastatic compression from its source should be considered of paramount importance. Since the majority of spinal cord compression involves firstly the ventral part of the sac, CD/AD are associated with better neurological outcomes and should be achieved in case of circumferential or anterior/anterolateral compression.

Pituitary surgery during Covid-19: a first hand experience and evaluation.

PURPOSE: During the Covid-19 pandemic every hospital has had to change its internal organization. Different institutions have highlighted the risks connected with endoscopic endonasal surgery. The goal of this paper is to illustrate the feasibility of pituitary region surgery during the SARS-CoV-2 pandemic. METHODS: After two negative Covid tests were obtained, three patients with macro GH-secreting tumors, and two patients with micro ACTH-secreting tumors resistant to medical treatment underwent surgery during the pandemic. During the surgery, every patient was treated as if they were positive. RESULTS: Neither operator, nor patient have developed Covid symptoms. The two neurosurgeons performing the operations underwent two Covid swab, which resulted negative. CONCLUSIONS: Pituitary surgery is a high risk non-urgent surgery. However, the method described has so far been effective and is safe for both patients and healthcare providers.

Spontaneous regression of calcified thoracic herniations: Can Hounsfield-units radiodensity have a predictive value?

INTRODUCTION: Spontaneous regressions of calcified thoracic disc herniations (TDH) have been rarely described. Since now, no previous papers hypothesized that radiological factors could be able to predict the evolution of the herniation. This study shows that the radiodensity of the herniated material in herniations with spontaneous resolution might differ from that of operated herniations. METHODS: This is a retrospective study. A cohort of patients that underwent surgical removal of a calcified thoracic disc herniation has been compared to two cases conservatively treated and a case with spontaneous regression. CT scans were evaluated to compute the average radiodensity [in Hounsfield units (HU)] of the calcified components of the herniations. All the slices of the CT scans involving the calcification were evaluated in their axial images and in their coronal and sagittal reformations. Comparison of the slices radiodensity (spontaneously resolved versus surgically treated) was performed with the unpaired Student's t test. RESULTS: The mean density of calcification in the case with spontaneous regression was found to be 454 HU. In the control group of surgical cases observed, and the conservatively treated cases, the mean HU density showed higher values (respectively, 827 and 853 HU) (p < 0.01). CONCLUSION: Qualitative differences between calcified TDH that resolve spontaneously or need surgical treatment might be shown by differences of radiodensity. This comparative study, in spite of the limitations due to small numbers, provides a new insight in the interpretation of the phenomenon of spontaneous resolution of calcified TDH. These slides can be retrieved under Electronic Supplementary Material.

The post-surgical era of GBM: How molecular biology has impacted on our clinical management. A review.

Glioblastoma (GBM) is the most common glioma in adults, with incidence increasing by 3% per year. According to the World Health Organization Classification of Central Nervous System Tumors, GBM is considered a grade IV tumor due to its malignant behavior. The aim of this review is to summarize the main biological aspects of GBM. In particular, we focused our attention on those alterations which have been proven to have an impact on patients' outcome, mainly in terms of overall survival (OS), or on the tumor response to therapies. We have also analyzed the cellular biology and the interactions between GBM and the surrounding environment.

Role of Nitric Oxide in Glioblastoma Therapy: Another Step to Resolve the Terrible Puzzle ?

Glioblastoma Multiforme, the most common and aggressive primary brain tumor, remains incurable despite of the advent of modern surgical and medical treatments. This poor prognosis depends by the recurrence after surgery and intrinsic or acquired resistance to chemotherapy and radiotherapy. Nitric oxide is a small molecule that plays a key roles in glioma pathophysiology. Many researches showing that NO is involved in induction of apoptosis, radiosensitization and chemosensitization. Therefore, NO role, if clarified, may improve the knowledge about this unsolved puzzle called GBM.

Double concentric craniotomy: Safe and effective technique to achieve an en bloc resection of tumor involving both skull and duraa.

INTRODUCTION: Many tumors can involve the skull. Meningiomas are one of the most common intracranial neoplasms and invasion of the bone was described in 49% of cases. Other neoplastic lesions that can arise in bone, or involve it, are metastases, hemangiomas, aggressive cutis carcinomas and sarcomas. Radical excision is the golden standard of treatment but elevating a bone flap when the tumor involves both the skull and the dura could represent a technical challenge. PRESENTATION OF CASE: We report the technical details of our approach to remove a meningioma involving both skull and dura in a man aged 45. Patient underwent gross total excision and cranioplasty with PEEK custom made prothesis (Synthes™). DISCUSSION: We describe a double concentric craniotomy (DCC) technique where the tumor involving the bone is before left in situ, exposing normal dura, to perform afterwards en-bloc excision with minimal traction of brain surface. CONCLUSION: DCC is a safe and effective technique to remove tumor involving both skull and dural structures under direct vision.

Results by motor cortex stimulation in treatment of focal dystonia, Parkinson's disease and post-ictal spasticity. The experience of the Italian Study Group of the Italian Neurosurgical Society.

Extradural motor cortex stimulation has been employed in cases of Parkinson's disease (PD), fixed dystonia (FD) and spastic hemiparesis (SH) following cerebral stroke. Symptoms of PD are improved by EMCS: results were evaluated on the basis of the UPDRS and statistically analysed. In PD EMCS is less efficacious than bilateral subthalamic nucleus (STN) stimulation, but it may be safely employed in patients not eligible for deep brain stimulation (DBS). The most rewarding effect is the improvement, in severely affected patients, of posture and gait. FD, unresponsive to bilateral pallidal stimulation, has been relieved by EDMS. In SH reduction of spasticiy by EMCS allows improvement of the motor function.

Posttraumatic epilepsy with special emphasis on prophylaxis and prevention.

Posttraumatic epileptic seizures have an incidence of about 10% in series of severe head injuries. Control of "early seizures", i.e. those occurring in the first week after injury, is mandatory. Attacks, especially if recurrent, may add secondary damage to the injured brain: intravenous phenythoin with therapeutic plasma level allows control of the attacks. Seizures occurring months or years after injury are called "late seizures": recurring "late seizures" make up the clinical syndrome of "posttraumatic epilepsy". "Prophylaxis" should mean that drug treatment, given for a more or less prolonged period of time, blocks permanently the ripening of the epileptogenic foci avoiding the occurrence of seizures. In animal "prophylaxis" by antiepileptic drugs seems efficacious in many experimental models including iron induced epilepsy which is considered a model of posttraumatic epilepsy and vice versa. In the human being "prophylaxis" has been attempted with: phenytoin, phenobarbital, carbamazepine, valproate but without success. During treatment period the occurrence of seizures is prevented but, after discontinuation of the drug, seizures occur just as in non treated patients. The ripening of the epileptic focus in posttraumatic epilepsy, as in iron induced epilepsy, seems to be due to a cascade of events beginning with haemorrhage, haemolysis, iron or heme compound liberation, free radical formation, peroxidation and cell death. Experimentally free radical scavengers and antiperoxidants have marked prophylactic effect. Some of them (phosphate diester of vitamin E and C, melatonin, vanillyl alcohol) may be employed in clinical practice, but up to date there is no controlled study in human beings.

Extradural motor cortex stimulation (EMCS) for Parkinson's disease. History and first results by the study group of the Italian neurosurgical society.

The preliminary results obtained by the Study Group for Treatment of Involuntary Movements by Extradural Motor Cortex Stimulation (EMCS) of the Italian Neurosurgical Society, are reported. The series includes 16 cases of very advanced Parkinson's Disease (PD), aged 46-81; 15 of them were not eligible for Deep Brain Stimulation. Ten cases have been evaluated at 3-30 months after implantation. Unilateral, sub-threshold extradural motor cortex stimulation (2 8 Volt, 100-400 microsec., 20-120 Hz) by chronically implanted electrodes, relieves, at least partially, but sometime dramatically, the whole spectrum of symptoms of advanced PD. Tremor and rigor bilaterally in all limbs and akinesia are reduced. Standing, gait, motor performance, speech and swallowing are improved. Benefit is marked as far as axial symptoms is concerned. Also the symptoms of Long Term Dopa Syndrome -dyskinesias, motor fluctuations - and other secondary effect of levodopa administration psychiatric symptoms - are improved. Levodopa dosage may be reduced by 50%. The effect seems persistent and does not fade away with time. Improvement ranged, on the basis of the UPDRS scale, from <25% to 75%. There was only one case of complete failure. Quality of life is markedly improved in patients who were absolutely incapable of walking and unable arise out of chair. After stimulation they could walk, even if assistance was necessary. Improvement was observed also in those with disabling motor fluctuation and dyskinesias which could be abolished.

MIB-1 immunoreactivity in craniopharyngiomas: a clinico-pathological analysis.

BACKGROUND: Craniopharyngiomas are epithelial tumors of the suprasellar region, unanimously defined as benign. Despite the benign histological aspect and apparent gross total resection achieved in a proportion of cases, recurrence rate remains about 30% at 10 years. The role of 7 pathological factors as predictors of recurrence and clinical outcome in craniopharyngioma patients is controversial, as well as the prognostic role of the evaluation of proliferation potential. MATERIAL AND METHODS: In the present study, the proliferation potential of 37 craniopharyngiomas was investigated by analyzing the pattern of Ki-67-MIBI immunoreactivity; the data have been analyzed in relation to age of the patient, histologic type (adamantinomatous/squamous papillary), microscopic and cytochemical features. RESULTS: Craniopharyngiomas operated in adults have a higher MIB-1-LI than those of children; the epithelial cells abutting the stromal cysts are engaged in the cell cycle, while this is not the case for the cells abutting the nervous tissue; MIB-1-LIs of adamantinomatous craniopharyngiomas are not different from those of squamous papillary craniopharyngiomas, the localization of MIB-1-positive nuclei is different in the 2 craniopharyngioma types, non-epithelial cells proliferate in the stromal component of craniopharyngiomas. CONCLUSIONS: By analyzing these data while considering all available information on the efficacy of surgery and radiotherapy, the proliferation potential of craniopharyngiomas, when evaluated by MIB-1, has no role in the outcome. The very low MIB-1-LI of the intracerebral tumor growth indicates that uncompletely resected tumor remnants do not represent an active starting point of recurrence.

Further experience with extradural motor cortex stimulation for treatment of advanced Parkinson's disease. Report of 3 new cases.

AIM: To report the results obtained with the extradural motor cortex stimulation in Parkinson's disease. METHODS: Three patients were submitted to MRI images and functional MRI in order to identify the upper limb motor area. Then a quadripolar electrostimulator was introduced in the extradural space, through 2 burr holes. RESULTS: Unilateral, extradural motor cortex stimulation relieves, at least partially, but sometime dramatically, the whole spectrum of symptoms in advanced Parkinson disease: tremor and rigor bilaterally in all limbs; akinesia; standing, anteropulsion, gait; motor performance; dysphagia; speech and swallowing. Also the symptoms of long term dopa syndrome--dyskinesias, and other secondary effect of L-dopa administration, psychiatric symptoms--are improved. CONCLUSION: The results seems do not fade away with time. Drug dosage may be reduced by 50%. We suggest early employ of transdural motor cortex stimulation.