Consensus statement from the international consensus meeting on post-traumatic cranioplasty.

BACKGROUND: Due to the lack of high-quality evidence which has hindered the development of evidence-based guidelines, there is a need to provide general guidance on cranioplasty (CP) following traumatic brain injury (TBI), as well as identify areas of ongoing uncertainty via a consensus-based approach. METHODS: The international consensus meeting on post-traumatic CP was held during the International Conference on Recent Advances in Neurotraumatology (ICRAN), in Naples, Italy, in June 2018. This meeting was endorsed by the Neurotrauma Committee of the World Federation of Neurosurgical Societies (WFNS), the NIHR Global Health Research Group on Neurotrauma, and several other neurotrauma organizations. Discussions and voting were organized around 5 pre-specified themes: (1) indications and technique, (2) materials, (3) timing, (4) hydrocephalus, and (5) paediatric CP. RESULTS: The participants discussed published evidence on each topic and proposed consensus statements, which were subject to ratification using anonymous real-time voting. Statements required an agreement threshold of more than 70% for inclusion in the final recommendations. CONCLUSIONS: This document is the first set of practical consensus-based clinical recommendations on post-traumatic CP, focusing on timing, materials, complications, and surgical procedures. Future research directions are also presented.

Pure Endoscopic Management of Fourth Ventricle Arachnoid Cyst: Case Report and Literature Review.

Arachnoid cysts (ACs) within the fourth ventricle are rare, and only a few cases have been reported in the literature. These are benign lesions within the arachnoid membrane, and they have been reported to occur in almost all locations where arachnoid is present. Different procedures have been performed to restore a normal cerebrospinal fluid dynamic and/or pressure, including shunting and partial or complete excision of the cyst by open microsurgery or endoscopic fenestration. We report the case of a fourth ventricle AC successfully treated using only endoscopic anterior trans-frontal cyst fenestration/marsupialization and standard third ventriculostomy. Clinical and technical features are discussed, along with the pertinent literature.

Primary pituitary neuroendocrine tumor: Case report and literature review.

BACKGROUND: Neuroendocrine tumors (NET) originate from the diffuse neuroendocrine system. These can arise in almost every organ of the body, although they are most commonly found in the gastrointestinal tract and respiratory system. The skull base and sellar region are extremely rare sites for neuroendocrine carcinoma. Consequently, in this case, both diagnosis and definition of surgical goals, as well as further treatment strategies were challenging. CASE DESCRIPTION: A 65-year-old woman was admitted to our Neurosurgery Department with a rapidly progressive visus reduction, drowsiness, polyuria, and polydipsia. Neuroimaging showed a sellar/suprasellar mass (diameter of 2 cm) with a heterogeneous signal compressing the optic chiasm and extending laterally toward the cavernous sinus. Differential diagnosis based on imaging included pituitary macroadenoma or metastasis. The patient underwent endoscopic endonasal transsphenoidal surgery. A total resection of the mass was impossible because of the infiltration of the optic chiasm and the intraoperative histological diagnosis of malignant epithelial neoplasm. Further histological evaluation revealed that the lesion was a NET with no other primary or metastatic sites detectable. Subsequently, the patient was successfully treated with fractioned stereotactic radiotherapy and polychemotherapy. Four years after the surgery, follow-up magnetic resonance imaging showed stability of the residual disease. Neurologic examination revealed a complete visual recovery. CONCLUSIONS: Primary pituitary NET, though rare, should be included in the differential diagnosis of sellar lesions. A multimodality treatment approach is needed. Finally, the present case highlights, that in the case of a pituitary lesion infiltrating the optic chiasm, including NET, the endoscopic endonasal transsphenoidal subtotal resection followed by fractioned stereotactic radiotherapy and chemotherapy may represent an effective and safe choice of treatment.

Anterior trans-frontal endoscopic management of colloid cyst: an effective, safe, and elegant way of treatment. Case series and technical note from a multicenter prospective study.

Different management options are available for the treatment of colloid cysts. Goals of those procedures are to achieve a complete resection avoiding potential long-term recurrence along with CSF pathways restoration with minimal morbidity and mortality. The two main surgical options are endoscopic resection or direct removal by either transfrontal or transcallosal approach. The efficacy of endoscopic technique to achieve gross total colloid cyst excision has been well documented. In the present study, authors describe a series of 29 patients who underwent surgery by a variation of the standard worldwide implemented endoscopic technique. Using a more anterior approach, it is easier to reach the roof of the cyst, its possible adherences with the tela choroidea, plexus, and the internal cerebral veins. The described approach has shown to be safe, quick, and very effective with a total cyst removal rate of 86.2%.

Expansion diverticulum of the suprapineal recess causing cerebellar ataxia. A case report.

As a result of long-standing cerebrospinal fluid (CSF) pulsation against the thinnest segments of the ventricular walls, focal enlargement of the ventricular system (diverticulum) may occur, mainly at the medial wall of the trigone of the lateral ventricles (atrial diverticula) or at the posterior wall of the third ventricle (expansion of the suprapineal recess). In the latter case, ocular signs are the most common symptoms, due to the severe deformation of the periaqueductal region. We describe a case of non-communicating hydrocephalus in a 36-year-old woman who presented a three-year history of cerebellar ataxia. Preoperative brain magnetic resonance (MR) scan showed marked supratentorial hydrocephalus with an apparently patent aqueduct of Sylvius, and an enlarged suprapineal recess causing cerebellar and tentorial dislocation. The patient was successfully treated by endoscopic third ventriculostomy and monitored by MR scans with phase-contrast sequences for assessment of CSF flow. Cerebellar ataxia is a very rare symptomatic onset for a suprapineal recess expansion diverticulum, which may cause obstructive hydrocephalus that can be effectively treated by endoscopic third ventriculostomy.

Analysis of MGMT promoter methylation status on intraoperative fresh tissue section from frameless neuronavigation needle biopsy of 25 patients with brain tumor.

Formalin fixation under conditions that adversely affected the quality of the DNA, or indeterminant assay, or extensive tumor necrosis can compromise the genetic analysis of a brain bioptic sample. The success of DNA extraction and Methyl Guanine Methyl Transferase (MGMT) promoter methylation testing could be improved by freezing of fresh tumor tissue at the moment of biopsy. To ensure an increased concentration of the DNA samples the withdrawal should be performed in an area with high probability of neoplastic cells. From May 2007 to January 2011 fifty-two frameless neuronavigation brain needle biopsy were performed at the Neurosurgery Unit of the "Arcispedale Santa Maria Nuova" City Hospital of Reggio Emilia. The "image-guided" neuronavigated protocol sampling provided withdrawal specimens highly correlated with neuroimaging characteristics of the lesions. In this study the Authors report the genetic analysis on 24 cases of freezing fresh tissue from brain needle bioptic sample starting from July 2008. The molecular determination of MGMT promoter was assessed with the Nested-Methylation Specific-Polymerase Chain Reaction on fresh or cryopreserved needle bioptic tissue. The genetic characterization was feasible in all the bioptic samples. The MGMT promoter was methylated in eleven patients, including a brain infection. The diagnostic yield of brain biopsy could be increased by the neuronavigated trajectories and the intraoperative frozen sections. In the future the availability of the molecular-genetic characterization of a brain tumor before open surgery will provide important information for the optimal treatment. The MGMT promoter status analysis on needle bioptic fresh tissue could be available also for that patient not eligible for surgical remotion of the tumor.

Calcium sulfate stimulates pulp stem cells towards osteoblasts differentiation.

Calcium sulfate (CaS) is a highly biocompatible material and enhances bone formation in vivo. However, how CaS alters osteoblast activity to promote bone formation is poorly understood. To study how CaS can induce osteoblast differentiation in mesenchymal stem cells, the expression levels of bone related genes and mesenchymal stem cells marker were compared in normal osteoblasts and dental pulp stem cells, using real time Reverse Transcription-Polymerase Chain Reaction. Gene differentially expressed between the two cells type were the trascriptional factor RUNX2, osteopontin (SPP1), COL1A1 (collagen type 1α1) and alkaline phosphatase (ALPL). The obtained results demonstrated that CaS strongly influences the behavior of DPSCs in vitro enhancing proliferation, differentiation and deposition of matrix.

Polylactide-polyglycolide resorbable plates stimulates adipose tissue-derived stem cells towards osteoblasts differentiation.

Polylactide, polyglycolide materials or devices have been utilized routinely during maxillofacial, craniofacial, and orthopaedic reconstructive surgical procedures.(1) These materials combine the benefits of rigid fixation with the advantages of biodegradation, avoiding the need for implant removal and minimizing the risk of other complications.(2) To study how polylactide, polyglycolide acids plates (PLPG plates) can induce osteoblast differentiation and proliferation in mesenchymal stem cells, the expression levels of bone related genes (RUNX2, SP7, ALPL, SPP1, COL1A1, COL3A1 and FOSL1) and mesenchymal stem cells marker (ENG) were measured in adipose derived stem cells (ADSCs) and normal osteoblast (NO) cultivated on PLPG plates after 15 and 30 days of treatment using real time Reverse Transcription-Polymerase Chain Reaction. Significantly differentially expressed genes among ADSCs and NO were SP7, ENG, FOSL1, RUNX, ALPL and SPP1 in the first 15 days of treatment and SP7, ENG FOSL1, COL3A1 COL1A1, SPP1 and ALPL after 30 days. The present study demonstrated that PLPG plates strongly influences the behavior of ADSCs in vitro by enhancing proliferation, differentiation and deposition of matrix.

MR-Cisternography with T2-Weighted Single-Shot Fast Spin Echo Sequence in the Diagnosis of a Spontaneous CSF Fistula of the Sphenoid Sinus Causing Massive Pneumocephalus.

A spontaneous CSF fistula of the sphenoid sinus was preoperatively diagnosed in a young woman presenting with massive pneumocephalus and rhinorrhea. Diagnosis was established by MR cisternography using a heavily T2-weighted 3D single-shot FSE sequence with half-Fourier analysis (3D-EXPRESS(®)), originally developed for imaging the inner ear. While unenhanced CT failed to detect the site of the fistula, MR permitted complete evaluation of the sellar/sphenoid region and tracked the CSF signal down to the nasal cavity.

[A useful panel in proliferative urothelial lesions: an analysis of cytokeratin 20, p53, CD44 and Ki-67 antigens]. / Panel di ausilio diagnostico nella patologia proliferativa uroteliale: studio degli antigeni citocheratina 20, p53, CD44 e Ki-67.

Urothelium can show several pseudoneoplastic lesions. Mimic lesions diagnosis is therapeutically and prognostically critical but it is often difficult on the basis of morphology alone in bladder biopsy specimen. We studied in a retrospective way an immunohistochemical panel that helps in this differential diagnosis. The panel includes antibodies against cytokeratin 20 (CK20), CD44, Ki67 (MIB-1) e p53 and we applied it to 31 cases of non-neoplastic urothelium (26 urothelial biopsies with reactive atypia and 5 normal urothelium) and 50 cases of urothelial neoplasia where we analized the distribution of the markers over the urothelium. We obtained two different "standard" results, for neoplastic and non-neoplastic urothelium. We were able to prove that this panel is useful, non expensive tool in the differential diagnosis of urothelial proliferative lesions.

Intracranial pressure patterns after endoscopic third ventriculostomy. Preliminary experience.

BACKGROUND: Endoscopic Third Ventriculostomy (ETV) has become the treatment of choice for non-communicating hydrocephalus as it is able to couple high success rate (60-80%) with rare complications (about 5%). Nevertheless, which is the best postoperative care standard and whether or not it is possible to predict the success of the procedure is still discussed. Traditional neuro-imaging techniques show several limitations in the early postoperative period. Indeed, a decrease of the ventricular size is often minimal and not visible before three weeks, while, MRI visualization of a flow void signal through the third ventricle floor, seems to have a significant incidence of false positives. The use of postoperative ICP measurement after ETV has been suggested as a valid monitoring method, mostly in the early postoperative period. In previously unpublished data the authors observed the existence of different ICP patterns following ETV. This finding prompted the authors to search for a relationship among ICP patterns, stoma functioning and prediction of success. METHOD: At our institution 26 consecutive patients affected by obstructive triventricular hydrocephalus underwent ETV. Among them there were 11 primitive aqueductal stenosis (AS), 5 shunt malfunctions, 2 third ventricle mass, 3 intraventricular cysts, and 5 patients with different lesions (1 quadrigeminal cistern arachnoidal cyst, 1 pineal region mass, 2 tectal tumours, and 1 supracerebellar abscess) compressing the aqueduct of Sylvius from outside named " ab estrinseco" aqueductal stenosis. All patients underwent postoperative Intra Cranial Pressure (ICP) monitoring by means of a ventricular catheter. FINDINGS: Transient ICP rises of any grade, mostly responsive to periodical liquoral subtractions, occurred shortly after ETV in as many as 50% of our patients. No major complications occurred. The effect of ETV on ICP trend was found to be variable among groups of patients thus identifying different ICP patterns. Patients with ab estrinseco Sylvian aqueduct compression showed the best effect on ICP, whilst, patients with intraventricular mass lesions causing triventricular hydrocephalus and shunt-dependent patients, revealed a clear trend to develop a more severe intracranial hypertension after ETV. CONCLUSIONS: Patients with shunt malfunction and patients with intraventricular mass lesions, showing a more pronounced trend to develop severe intracranial hypertension after ETV, should always be considered for postoperative ICP monitoring in order to detect and, eventually, treat any ICP rises which may occur. Unfortunately, it is still difficult to assign a predictive value to the different postoperative ICP patterns. The authors encourage postoperative ICP monitoring in all patients in order to define all the possible ICP patterns following ETV.

Exclusively intracranial and cranial fasciitis of the adult age.

The unusual case of an exclusively intracranial localization of fasciitis (CF) in a man aged 47 is reported. The cystic lesion had been accidentally discovered 10 years before when the patient sustained a contralateral ischemic stroke; the cyst, being absolutely silent, was not operated on at that time. After 10 years, the patient complained of seizures and mild right-sided paresis. CT scan revealed a dramatic increase of the lesion whose mass effect caused an initial subfalcial herniation of the brain. The mass was grossly removed, the patient recovered and become seizure-free. CF, rare in childhood, is exceptional in the adult age. The importance of a correct histological diagnosis is hereby stressed, because CF is absolutely benign, self-limiting, and does not require further treatment, but may be misdiagnosed as sarcoma.

Intracranial pressure monitoring after endoscopic third ventriculostomy: an effective method to manage the 'adaptation period'.

Endoscopic third ventriculostomy (ETV) has become the treatment of choice for non-communicating hydrocephalus. Nevertheless, which technique should be considered of choice to identify features correlating with the failure of an endoscopic procedure and which is the optimal postoperative period care standard are still a matter of debate. Traditional neuroimaging techniques have several limitations in assessing the success of the procedure mostly in the early postoperative period. Indeed, a decrease in the ventricular size is often minimal and not visible before 3-4 weeks. MRI, able to detect the presence of a flow void signal through the third ventricle floor, has been reported to have a significantly high incidence of false positives. In our experience, the continuous measuring of intracranial pressure (ICP) by means of a ventricular catheter has been of great help in verifying the correct functioning of the communication between the ventricle and the subarachnoidal spaces during the first postoperative days. Furthermore, ICP monitoring allowed us to safely deal with the intracranial hypertension that may occur shortly after ETV.

Protein kinase C-dependent in vivo phosphorylation of prourokinase leads to the formation of a receptor competitive antagonist.

We recently reported that in vivo phosphorylation of urokinase-type plasminogen activator on Ser138/303 prevents its catalytic-independent ability to promote myelomonocytic cell adherence and motility. We now show that Ca2+ activated, phospholipid-dependent protein kinase C from rat brain phosphorylates in vitro a peptide corresponding to prourokinase residues 133-143 (DGKKPSSPPEE) and the full-length molecule on Ser138/139. The in vivo involvement of the protein kinase C isoenzyme family is supported by the finding that inhibition of kinase C activity prevents prourokinase phosphorylation on Ser138/303 in A431 human carcinoma cells. Conversely, a short treatment of A431 cells with phorbol myristate acetate increases the extent of phosphorylated prourokinase and, concomitantly, affects its function; under these conditions, the capability of prourokinase to up-regulate U937 monocyte-like cell adherence is severely impaired, although receptor binding is unaltered. By the aid of a "phosphorylation-like" variant (Ser138 to Glu) we show that modification of Ser138 is sufficient to confer to prourokinase the antagonistic properties observed following in vivo stimulation of protein kinase C activity. These observations provide the first evidence that protein kinase C directs the formation of a receptor competitive antagonist by regulating the in vivo phosphorylation state of prourokinase.

Phosphorylation of human pro-urokinase on Ser138/303 impairs its receptor-dependent ability to promote myelomonocytic adherence and motility.

Serine phosphorylation of human pro-urokinase (pro-uPA) by A431 human carcinoma cells results in a catalytically active molecule with reduced sensitivity to plasminogen activator inhibitor type 1. We mapped the phosphorylated seryl residues by analyzing the in vivo phosphorylation state of engineered pro-uPA variants carrying a COOH-terminal poly-histidine tag. Stably transfected A431 cells do not incorporate radioactive phosphate into tagged pro-uPA in which the serines 138 and 303 have been replaced with glutamic residues, although endogenous nontagged pro-uPA is 32P-labeled on A and B chains. Moreover, the catalytic-independent ability of the mono- and di-substituted "phosphorylation-like" variants to bind to the GPI-anchored urokinase receptor (uPAR) and promote adherence of differentiating U937, HL-60, and THP-1 myelomonocytic cells was examined. We found that glutamic residues as well as the naturally occurring phosphoserines at positions 138 and 303 abolish proadhesive ability, although they do not interfere with receptor binding. In addition, pro-uPA carrying Glu138/303 lacks the capability to induce a chemotactic response of THP-1 cells. The exclusive presence of Glu138 reduces pro-uPA proadhesive and chemotactic ability by 70-80%, indicating that a phosphoserine residue at the same position plays a major inhibitory role of myeloid cell response to pro-urokinase. The di-substitution does not affect pro-uPA ability to interact with vitronectin or to enhance binding of urea-denatured vitronectin to uPAR. However, unlike wild-type tagged pro-uPA, the di-substituted variant does not induce receptor polarization in pre-adherent U937 cells. Taken together, the data support the possibility that pro-uPA phosphorylation on Ser138/303 can modulate uPAR transducing ability.

Cyclandelate in the prophylaxis of migraine: a randomized, parallel, double-blind study in comparison with placebo and propranolol. The Study group.

Cyclandelate inhibits calcium-induced contraction of vascular smooth muscle cells, platelet aggregation induced by thrombin, platelet-activating-factor and adenosine, and also suppresses a provoked 5HT release from platelets. This pharmacological profile suggests that cyclandelate may have a potential prophylactic effect in migraine. To test this hypothesis, a double-blind multicentre study was performed in 214 patients to investigate the efficacy and tolerability of cyclandelate compared to placebo and propranolol. After a 4-week baseline period, eligible patients (randomization 3:2:3) were treated for 12 weeks with daily doses of 1.200 mg cyclandelate (n = 81), placebo (n = 55) or 120 mg propranolol (n = 78). The number of migraine attacks (> or = 50% responders) and the migraine duration/month were compared based on the difference between baseline and the last 4 weeks of prophylactic treatment. The percentage of patients with a reduction in migraine attacks of > or = 50% treated with cyclandelate (37.0%) or propranolol (42.3%) was not significantly superior to placebo (30.9%; p > 0.025). The mean duration of migraine in hours (h) per month decreased in both active treatment groups (cyclandelate: 36.8 h, p = 0.046; propranolol: 34.4 h, p = 0.039) compared to placebo (13.7 h) without reaching statistical significance (alpha/2 = 0.025). The clinical efficacy of cyclandelate and propranolol was comparable. Adverse experiences were reported by 13 patients (16.0%) treated with cyclandelate, by 5 patients (9.1%) treated with placebo and by 19 patients (24.4%) treated with propranolol. These were drug-related in 7.1% (n = 6) of patients treated with cyclandelate and in 9% (n = 7) of patients treated with propranolol. In summary, cyclandelate has a comparable efficacy to that of propranolol, an established drug of first choice in the prophylaxis of migraine. Both drugs were better than placebo, but not significantly so. Both active treatments were well tolerated.

Tissue expansion in neurosurgical reconstructive technique: case report.

BACKGROUND: Various reconstructive techniques using hair-bearing scalp to manage unsightly scalp defects have been described. In 1983, Fonseca and in 1984, Horowitz emphasized the use of galeal-pericranial flaps in scalp wounds with exposed bone. In 1986, Matthews and Missoten described early tissue expansion to close a traumatic defect of the scalp, and in 1990 Kiyono placed tissue expander in a pocket adjacent to the defect that was covered with Marlex Mesh. METHODS: The authors present a case of 23-year-old man with a scalp laceration over a depressed fracture of the skull and a dural tear, after a traffic accident. The repair procedures at another hospital failed, resulting in an area of scalp necrosis with a cerebrospinal fluid (CSF) leak. At our observation, the reconstructive technique using hair-bearing scalp with tissue expander was performed to manage unsightly scalp necrosis. Moreover the neurosurgical treatment was necessary to avoid the complications of the CSF leak. CONCLUSIONS: A 9-year review showed more than 40 patients treated by this technique that allows a pericranial flap of every size. When scalp defects are too large, the tissue expander allows good aesthetic results.

[Long-term efficacy and side effects of various migraine prophylactics: a retrospective analysis.]. / Langzeitwirksamkeit und Nebenwirkungen verschiedener Migräneprophylaktika-eine retrospektive Analyse.

INTRODUCTION: Drug therapy for the prevention of migraine attacks is becoming more and attacks is becoming more and more important. The aims of such prophylactic treatment are to reach a lower frequency, shorter duration and milder intensity of migraine attacks, and to reduce the intake of anti-migraine medication, to improve the quality of life and working ability. The question of efficacy and tolerance of established migraine prophylactics [1] has been thoroughly investigated in many studies. So far the question of sustained efficacy after a successful prophylactic treatment completion has not been a research priority, but it is nonetheless of great importance. Researchers at the neurologic scientific research institute of the university of Naples have followed up migraine out-patients after successful prophylactic treatment and observed that prophylactic agents differ not only in their immediate efficacy and safety, but also in long-term efficacy. Therefore, an open pilot study was performed with the prophylactic agents propranolol, flunarizine, pizotifen, DHE retard, methysergide and cyclandelate in the recommended dossages (Tabe 1). OBJECTIVE AND METHODS: The aim of this study was to determine whether the various prophylactic agents available differ in active and long-term efficacy (at the end of a period after a successful prophylaxis=follow-up) and in the distribution of long-term responders at the end of the follow-up. The side effects of all prophylactic agents during active prophylaxis were also compared. Initially, 387 outpatients who had successfully completed a period of prophylactic treatment were recruited, and 208 were included in the study. At the time of follow-up a further period of prophylactic treatment was recommended if the efficacy rate was lower than 40% of the baseline at the end of the active prophylaxis period. The patients kept migraine headache daries (MHD) during the active prophylaxis and the follow-up, recording the following migraine objectives: number of attacks, pain total index (PTI), frequency of awakening with headache, and use of analgesics. RESULTS: The results showed that cyclandelate-actually a drug that is not yet officially accepted-had especially good results from the aspects of immediate efficacy, long-term efficacy and tolerance, compared with all other prophylactic agents. Significant differences were found in the duration of active prophylaxis. The mean monthly duration for patients treated with pizotifen (4.2), cyclandelate (3.9), and DHE retard (3.8) was longer than for those treated with flunarizine (2.8), and for patients treated with pizotifen it was longer than for those receiving propranolol (3.4). The mean duration (in months) of the postprophylactic period was distinctly longer for patients treated with cyclandelate (18.2) than for patients treated with DHE retard (12.9), flunarizine (13.1), propranolol (13.3) or pizotifen (13.8), but comparable with that after methysergide (17.2). Among the 208 patients, 85 were long-term responders (with no indication for repeated prophylaxis). No significant differences were found between the various groups, but the group of patients treated with cyclandelate was the only one with more than 50% long-term responders (18 vs 14). In general, the side effects of pizotifen, flunarizine and DHE retard seemed to be most pronounced. For cyclandelate, propranolol and methysergide fewer side effects were reported. CONCLUSION: In spite of the uncontrolled pilot design, it can be said in summary that all prophylactic drugs were effective. Cyclandelate had a good safety profile, and in efficacy it was at least comparable to the other prophylactic drugs. Patients treated with cyclandelate had a longer duration of active treatment and likewise a longer period of follow up. In addition, the proportion of patients with "no indication for repeated prophylaxis" at follow up was higher than for any of the other drugs. The results are interesting for medical practice and suggest replication in a randomized blind study. If the results yielded by the present study are confirmed, cyclandelate should be classified as a drug of first choice for migraine prophylaxis.