Supramaximal resection: retrospective study on IDH-wildtype Glioblastomas based on the new RANO-Resect classification.

BACKGROUND: The prognostic value of the extent of resection in the management of Glioblastoma is a long-debated topic, recently widened by the 2022 RANO-Resect Classification, which advocates for the resection of the non-enhancing disease surrounding the main core of tumors (supramaximal resection, SUPR) to achieve additional survival benefits. We conducted a retrospective analysis to corroborate the role of SUPR by the RANO-Resect Classification in a single center, homogenous cohort of patients. METHODS: Records of patients operated for WHO-2021 Glioblastomas at our institution between 2007 and 2018 were retrospectively reviewed; volumetric data of resected lesions were computed and classified by RANO-Resect criteria. Survival and correlation analyses were conducted excluding patients below near-total resection. RESULTS: 117 patients met the inclusion criteria, encompassing 45 near-total resections (NTR), 31 complete resections (CR), and 41 SUPR. Median progression-free and overall survival were 11 and 15 months for NTR, 13 and 17 months or CR, 20 and 24 months for SUPR, respectively (p < 0.001), with inverse correlation observed between survival and FLAIR residual volume (r -0.28). SUPR was not significantly associated with larger preoperative volumes or higher rates of postoperative deficits, although it was less associated with preoperative neurological deficits (OR 3.37, p = 0.003). The impact of SUPR on OS varied between MGMT unmethylated (HR 0.606, p = 0.044) and methylated (HR 0.273, p = 0.002) patient groups. CONCLUSIONS: Results of the present study support the validity of supramaximal resection by the new RANO-Resect classification, also highlighting a possible surgical difference between tumors with methylated and unmethylated MGMT promoter.

A randomized prospective comparative study on sinonasal morbidity and quality of life of transsphenoidal endoscopic surgery for pituitary adenomas: endonasal versus trans-septal approach.

PURPOSE: Endoscopic endonasal transsphenoidal approach (Endonasal approach) is commonly used to treat pituitary adenomas. The extent of dissection possibly changes the anatomy and the physiology of the nasal cavities and could give rise to post-operative morbidity and the quality of life (QoL). The purpose of this study was to investigate sinonasal morbidity and general QoL in patients who underwent surgery for treatment of pituitary adenoma, comparing Endonasal and endoscopic trans-septal transsphenoidal approach (Trans-septal approach). METHODS: A prospective observational study, recruiting 40 patients undergoing surgery for pituitary adenoma, 20 via Endonasal approach and 20 via Trans-septal approach at our institution. Surveys with Sinonasal Outcome Test-22 (SNOT-22), Chronic Sinusitis Survey (CSS), and Short Form Health Survey 36 version 2 (SF-36v2) were obtained to collect QoL data pre- and postoperatively. RESULTS: All the 40 patients completed the questionnaires. At 6 months postoperatively, the SNOT-22 and CSS score shows significant improvements both in Endonasal approach (p = 0.01) and in Trans-septal approach (p = 0.02). No significant difference in sinonasal morbidity is observed between the two groups for SNOT-22 (p = 0.13) and CSS scores, except for sinus headache (p = 0.49), with a better score in Endonasal approach. The mean SF-36v2 scores remain the same in pre- and post-operative periods, but an improvement in time is seen in general health (p = 0.027), and general health compared to one year ago (p < 0.001). CONCLUSIONS: Endoscopic transsphenoidal surgery has negligible morbidity and does not negatively affect the nasal function in the long term. Endonasal approach and Trans-septal approach are comparable in terms of morbidity outcomes and general QoL, leaving the choice of the approach to the surgeon preference.

Petroclival Clinoidal Folds and Relationships with Arachnoidal Membranes of Anterior and Middle Incisural Spaces: Old Neuroanatomical Terms for a New Neurosurgical Speech in Cadaver Labs with Limited Resources Era. Part II: Free Edge of the Tentorium, Petroclinoid Folds, and Incisural Spaces.

BACKGROUND Anatomical dissections play an irreplaceable role in the training of new generations of effective neurosurgeons, especially when addressing skull base lesions is required.The Authors describe an inter-laboratory dissection study aimed at improving the knowledge of a complex region of the skull base. The anterior and middle incisural spaces are of remarkable anatomical and surgical interest due to complex relationships between bony, dural, arachnoidal, and neurovascular structures. The primary purposes of this study are to describe the anatomy of this region with particular emphasis on the relationships between the anterior margin of the free edge of the tentorium and the sphenoid and petrous bone; to identify surgical implications in many different types of neurosurgical procedures dealing with this challenging, complex anatomic area.METHODS Thirteen anatomical specimens, including five injected specimens, were dissected in this study. In the formalin-fixed specimens, vessels were injected with colored silicone.RESULTS The anatomical study was focused on the description of the relationships between bony dural, arachnoid, and neurovascular structures. Surgical implications are described accordingly.CONCLUSIONS Detailed anatomical knowledge of this region finds concrete applications in neurosurgical practice since the anterior and middle incisural spaces are often surgically exposed in neoplastic and vascular diseases. The high-definition pictures reported in this study could represent useful support to understand the anatomy of this complex region.Finally, our study could provide guidance to neurosurgical centers in which resources are limited that are either planning to establish their own cadaver dissection laboratory or failed to do so because of the supposed high-costs.

Petroclival Clinoidal Folds and Relationships with Arachnoidal Membranes of Medial Incisural Space: Old Neuroanatomical Terms for a New Neurosurgical Speech in Cadaver Labs with Limited Resources Era. Part III: Arachnoid Membranes, Cranial Nerves, and Surgical Implications.

BACKGROUND Anatomical dissections play an irreplaceable role in the training of new generations of effective neurosurgeons, especially when addressing skull base lesions is required.The Authors describe an inter-laboratory dissection study aimed at improving the knowledge of a complex region of the skull base. The anterior and middle incisural spaces are of remarkable anatomical and surgical interest due to complex relationships between bony, dural, arachnoidal, and neurovascular structures. The primary purposes of this study are to describe the anatomy of this region with particular emphasis on the relationships between the anterior margin of the free edge of the tentorium and the sphenoid and petrous bone; to identify surgical implications in many different types of neurosurgical procedures dealing with this challenging complex anatomic area.METHODS Thirteen anatomical specimens, including five injected specimens, were dissected in this study. In the formalin-fixed specimens, vessels were injected with colored silicone.RESULTS The anatomical study focused on the description of the relationships between bony dural, arachnoid, and neurovascular structures. Surgical implications are described accordingly.CONCLUSIONS Detailed anatomical knowledge of this region finds concrete applications in neurosurgical practice since the anterior and middle incisural spaces are often surgically exposed in neoplastic and vascular diseases. The high-definition pictures reported in this study could represent useful support to understand the anatomy of this complex region.Finally, our study could provide guidance to neurosurgical centers in which resources are limited that are either planning to establish their own cadaver dissection laboratory or failed to do so because of the supposed high-costs.

Medial thalamotomy using stereotactic radiosurgery for intractable pain: a systematic review.

Medial thalamotomy using stereotactic radiosurgery (SRS) is a potential treatment for intractable pain. However, the ideal treatment parameters and expected outcomes from this procedure remain unclear. The aim of this systematic review is to provide further insights on medial thalamotomy using SRS, specifically for intractable pain. A systematic review was performed to identify all clinical articles discussing medial thalamotomy using SRS for intractable pain. Only studies in which SRS was used to target the medial thalamus for pain were included. For centers with multiple publications, care was taken to avoid recounting individual patients. The literature review revealed six studies describing outcomes of medial thalamotomy using SRS for a total of 125 patients (118 included in the outcome analysis). Fifty-two patients were treated for cancer pain across three studies, whereas five studies included 73 patients who were treated for nonmalignant pain. The individual studies demonstrated initial meaningful pain reduction in 43.3-100% of patients, with an aggregate initial meaningful pain reduction in 65 patients (55%) following SRS medial thalamotomy. This effect persisted in 45 patients (38%) at the last follow-up. Adverse events were observed in six patients (5%), which were related to radiation in five patients (4%). Medial thalamotomy using SRS is effective for select patients with treatment-resistant pain and is remarkably safe when modern radiation delivery platforms are used. More posteriorly placed lesions within the medial thalamus were associated with better pain relief. More studies are warranted to shed light on differences in patient responses.

Neurosurgery during the Greco-Italian War (World War II): the management of war-related head injuries at the Italian field hospital of Sinanaj in Albania.

During the Greco-Italian War (World War II [WWII], 1940-1941), an Italian field hospital was set up in Sinanaj, Albania. The hospital's military surgeons carefully collected information about the characteristics and management of patients with war-related injuries. In 1942, they published a detailed report, with a section dedicated to the management of war-related head injuries. The aim of this report is to analyze that section, to describe the characteristics and neurosurgical management of war-related head injuries, and to depict the status of war neurosurgery in the Royal Italian Army during WWII. The analysis revealed that, during the Greco-Italian War (November 1940-April 1941), 149 patients with war-related head injuries were admitted to the Sinanaj hospital, and 48 patients underwent surgery. Head injuries were caused by bomb fragments in 126 patients, bullets in 5 patients, and other causes (falls from height, vehicle accidents, or rock fragments) in 18 patients. Six patients (12.5%) died after surgery. Before surgery, patients underwent resuscitation with blood transfusions and fluid. Preoperatively, a plain head radiograph was usually acquired to locate metallic and bone fragments. The surgical technique consisted of craniotomy or craniectomy, aggressive debridement of metallic and bone fragments, and watertight dural closure. Surgical drainage, overall aseptic technique, serial spinal taps, and perioperative antibiotics were used to prevent infections. The surgical aims and technique used by the Italian surgeons for the management of head injuries were similar to those of the Allied surgeons during WWII. Operative mortality was also comparable. Although the surgical technique for war-related head injuries has evolved since WWII, many aspects of the technique used by the Italian and Allied surgeons during WWII are still in the standard of care today.

The ipsilateral interhemispheric transprecuneal approach: microsurgical anatomy, indications, and neurosurgical applications.

Surgical treatment of intraventricular lesions is challenging because of their deep location, vascularization, and their complex relationships with white matter fibers. The authors undertook this study to describe the microsurgical anatomy of the white matter fibers covering the lateral wall of the atrium and temporal horn and to demonstrate how the ipsilateral interhemispheric transprecuneal approach can be safely used to remove lesions of this region sparing the anatomo-functional integrity of the fibers themselves. A detailed description of the approach including operative measurements is also given. The Klingler' technique with progressive identification of white matter fibers covering the lateral wall of the atrium and temporal horn was performed on ten formalin-fixed human hemispheres. Then, ten fresh, non-formalin-fixed non-silicon-injected adult cadaveric heads were analyzed for the simulation of the ipsilateral interhemispheric transprecuneal approach. Three illustrative cases are presented. The simulation of the interhemispheric transprecuneal approach on ten fresh non-formalin-fixed specimens showed that a 10 to 20 mm corticotomy perpendicular to the parieto-occipital sulcus at the junction with the cingulum allows a wide corridor for the exposure of the entire atrial cavity and the posterior third of the temporal horn. The ipsilateral interhemispheric transprecuneus approach represents a safe and effective option for tumors involving the atrium and the posterior third of the temporal horn.

Microsurgical versus endoscopic trans-sphenoidal approaches for clivus chordoma: a pooled and meta-analysis.

Chordoma is a rare slow-growing neoplastic bone lesion. However, they show an invasive local growth and high recurrence rate, leading to an overall survival rate of 65% at 5 years and 35% at 10 years. We conducted a pooled and meta-analysis comparing recurrence rate, post-operative-complications, and survival in patients undergoing either microsurgical (MA) or endoscopic approaches (EA). Search of literature was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify surgical series of clivus chordomas published between January 1990 and March 2018 on Pubmed, Scopus, and Cochrane. Two different statistical analyses have been performed: a pooled analysis and a single-arm meta-analysis of overall recurrence rate and subgroup meta-analysis of complications in the subgroups open surgery and endoscopic surgery. After full-text screening, a total of 58 articles were included in the pooled analysis and 27 studies were included for the study-level meta-analysis. Pooled analysis-the extent of resection was the only association that remained significant (subtotal: HR = 2.18, p = 0.004; partial: HR = 4.40, p < 0.001). Recurrence was more prevalent among the surgical patients (45.5%) compared to endoscopic ones (23.7%). Meta-analysis-results of the cumulative meta-analysis showed an overall rate of recurrence of 25.6%. MA recurrence rate was 31.8% (99% CI 14-52.8), EA recurrence rate was 19.4% (5.4-39.2). CSF leak rate for the endoscopic group was 10.3% (99%CI 5-17.3) and 9.5% (99%CI 1.2-24.6) for the open surgery group. The partial removal versus total removal has an influence on recurrence rate (p < 0.001). MA recurrence rate was 31.8%; EA recurrence rate was 19.4%. The extent of resection is confirmed as a statistically significant factor affecting the risk for recurrence both with the pooled analysis and with the meta-analysis. Meta-analysis demonstrated that older patients tend to recur more than young patients, especially in surgical group.

Treatment of patients with glioma during the COVID-19 pandemic: what we learned and what we take home for the future.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) has changed the way in which cancer is treated. Patients with high-grade glioma (HGG) are believed to be in a vulnerable category. The aim of this study was to describe the experience of a hub cancer center and the measures that were put in place for treatment of patients with newly diagnosed and recurrent glioma. METHODS: To prevent in-hospital contagion and preserve the safety of health professionals and patients, specific protocols and strict regulations were introduced. Physical distancing, use of surgical masks, and diligent hand hygiene were adopted. Each case was discussed in a multidisciplinary board meeting before treatment. All patient candidates for surgical procedures were tested for SARS-CoV-2 with a nasopharyngeal swab and a chest CT scan. Indications for surgery were the radiological suspicion of HGG in patients with a good performance status and/or the rapid and progressive occurrence of neurological deficits. Adjuvant treatments were performed only in cases of HGG. This therapy consisted of conventional fractional radiotherapy (RT; 60 Gy/30 fractions) with concomitant and adjuvant temozolomide chemotherapy (TMZCHT) in younger patients; in elderly patients, a short course of RT was employed (40.5 Gy/15 fractions). For recurrent HGG, treatments were assessed after a careful evaluation of the patient's general condition, neurological status, and risk of early impairment in neurological status if not treated. During simulation CT for the RT plan, each patient underwent a chest CT study. In cases in which an imaging study was suspicious for COVID-19 pneumonia, the patient was immediately isolated and rapidly underwent nasopharyngeal swab testing. RESULTS: Between March 1 and April 30, 2020, 23 HGGs were treated, and these cases are included in the present evaluation. Fifteen patients harboring newly diagnosed glioblastoma (GBM) underwent resection followed by a regimen of chemotherapy and RT, and 3 patients with newly diagnosed anaplastic oligodendroglioma underwent surgery followed by adjuvant RT. Five patients were treated for recurrent GBM, and they received surgery plus adjuvant RT. One patient in whom the simulation CT study was suspicious for COVID pneumonia was tested with a nasopharyngeal swab, which proved positive for SARS-CoV-2 infection. No patients contracted COVID-19 during hospitalization for surgery or during RT treatment. Corticosteroid therapy was administered to all patients beginning on the 1st day of RT. CONCLUSIONS: The authors' experience during the COVID-19 pandemic showed that patients with HGG can be treated in the most effective manner without a compromise in safety. Careful selection criteria and a multidisciplinary evaluation are pivotal to assessing the optimal therapeutic strategy.

A comparison of publication to TBI burden ratio of low- and middle-income countries versus high-income countries: how can we improve worldwide care of TBI?

OBJECTIVE: Traumatic brain injury (TBI) is a global public health problem and more than 70% of trauma-related deaths are estimated to occur in low- and middle-income countries (LMICs). Nevertheless, there is a consistent lack of data from these countries. The aim of this work is to estimate the capacity of different and heterogeneous areas of the world to report and publish data on TBI. In addition, we wanted to estimate the countries with the highest and lowest number of publications when taking into account the relative TBI burden. METHODS: First, a bibliometric analysis of all the publications about TBI available in the PubMed database from January 1, 2008, to December 31, 2018, was performed. These data were tabulated by country and grouped according to each geographical region as indicated by the WHO: African Region (AFR), Region of the Americas (PAH), South-East Asia Region (SEAR), European Region (EUR), Eastern Mediterranean Region (EMR), and Western Pacific Region (WPR). In this analysis, PAH was further subdivided into Latin America (AMR-L) and North America (AMR-US/Can). Then a "publication to TBI volume ratio" was derived to estimate the research interest in TBI with respect to the frequency of this pathology. RESULTS: Between 2008 and 2018 a total of 8144 articles were published and indexed in the PubMed database about TBI. Leading WHO regions in terms of contributions were AMR-US/Can with 4183 articles (51.36%), followed by EUR with 2003 articles (24.60%), WPR with 1507 (18.50%), AMR-L with 141 articles (1.73%), EMR with 135 (1.66%), AFR with 91 articles (1.12%), and SEAR with 84 articles (1.03%). The highest publication to TBI volume ratios were found for AMR-US/Can (90.93) and EUR (21.54), followed by WPR (8.71) and AMR-L (2.43). Almost 90 times lower than the ratio of AMR-US/Can were the ratios for AFR (1.15) and SEAR (0.46). CONCLUSIONS: An important disparity currently exists between countries with a high burden of TBI and those in which most of the research is conducted. A call for improvement of data collection and research outputs along with an increase in international collaboration could quantitatively and qualitatively improve the ability of LMICs to ameliorate TBI care and develop clinical practice guidelines.

Multiple brain metastases: a surgical series and neurosurgical perspective.

Despite review papers claim for radical treatment of oligometastatic patients, only few surgical series have been published. In this study, we analyze results and actual role of surgical resection for the management of patients with multiple brain metastases. This retrospective study compares surgical results of two groups of patients consecutively treated in our Institute from January 2004 to June 2015. The first group comprises all 32 patients with multiple brain metastases with only 2-3 lesions who underwent surgical resection of all lesions; the second group comprises 30 patients with a single surgically treated brain mestastasis compatible with the first group (match-paired control series). Median survival was 14.6 months for patients with multiple brain metastases (range 1-28 months) and 17.4 months for patients with a single brain metastasis (range 4-38 months); the difference was not statistically significant (P = 0.2). Neurological condition improved in 59.4% of patients with multiple metastases, it remained unchanged in 37.5% and worsened in 3.1%. In our series, selected patients with only 2-3 lesions with well-controlled systemic disease, life expectancy of more than 3 months, Karnofsky's performance status > 60, and surgically accessible lesions, benefited from surgical treatment in terms of survival and quality of life, with reduction or disappearance of significant neurological deficits. The prognosis for these patients is similar to that of patients with a single metastasis. It seems that patients with breast cancer included in our series had the worst prognosis if compared to other histotypes.

Microduplications at the pseudoautosomal SHOX locus in autism spectrum disorders and related neurodevelopmental conditions.

BACKGROUND: The pseudoautosomal short stature homeobox-containing (SHOX) gene encodes a homeodomain transcription factor involved in cell-cycle and growth regulation. SHOX/SHOX enhancers deletions cause short stature and skeletal abnormalities in a female-dominant fashion; duplications appear to be rare. Neurodevelopmental disorders (NDDs), such as autism spectrum disorders (ASDs), are complex disorders with high heritability and skewed sex ratio; several rare (<1% frequency) CNVs have been implicated in risk. METHODS: We analysed data from a discovery series of 90 adult ASD cases, who underwent clinical genetic testing by array-comparative genomic hybridisation (CGH). Twenty-seven individuals harboured CNV abnormalities, including two unrelated females with microduplications affecting SHOX. To determine the prevalence of SHOX duplications and delineate their associated phenotypic spectrum, we subsequently examined array-CGH data from a follow-up sample of 26 574 patients, including 18 857 with NDD (3541 with ASD). RESULTS: We found a significant enrichment of SHOX microduplications in the NDD cases (p=0.00036; OR 2.21) and, particularly, in those with ASD (p=9.18×10(-7); OR 3.63) compared with 12 594 population-based controls. SHOX duplications affecting the upstream or downstream enhancers were enriched only in females with NDD (p=0.0043; OR 2.69/p=0.00020; OR 7.20), but not in males (p=0.404; OR 1.38/p=0.096; OR 2.21). CONCLUSIONS: Microduplications at the SHOX locus are a low penetrance risk factor for ASD/NDD, with increased risk in both sexes. However, a concomitant duplication of SHOX enhancers may be required to trigger a NDD in females. Since specific SHOX isoforms are exclusively expressed in the developing foetal brain, this may reflect the pathogenic effect of altered SHOX protein dosage on neurodevelopment.

Ohnologs are overrepresented in pathogenic copy number mutations.

A number of rare copy number variants (CNVs), including both deletions and duplications, have been associated with developmental disorders, including schizophrenia, autism, intellectual disability, and epilepsy. Pathogenicity may derive from dosage sensitivity of one or more genes contained within the CNV locus. To understand pathophysiology, the specific disease-causing gene(s) within each CNV need to be identified. In the present study, we test the hypothesis that ohnologs (genes retained after ancestral whole-genome duplication events, which are frequently dosage sensitive) are overrepresented in pathogenic CNVs. We selected three sets of genes implicated in copy number pathogenicity: (i) genes mapping within rare disease-associated CNVs, (ii) genes within de novo CNVs under negative genetic selection, and (iii) genes identified by clinical array comparative genome hybridization studies as potentially pathogenic. We compared the proportion of ohnologs between these gene sets and control genes, mapping to CNVs not known to be disease associated. We found that ohnologs are significantly overrepresented in genes mapping to pathogenic CNVs, irrespective of how CNVs were identified, with over 90% containing an ohnolog, compared with control CNVs >100 kb, where only about 30% contained an ohnolog. In some CNVs, such as del15p11.2 (CYFIP1) and dup/del16p13.11 (NDE1), the most plausible prior candidate gene was also an ohnolog, as were the genes VIPR2 and NRXN1, each found in short CNVs containing no other genes. Our results support the hypothesis that ohnologs represent critical dosage-sensitive elements of the genome, possibly responsible for some of the deleterious phenotypes observed for pathogenic CNVs and as such are readily identifiable candidate genes for further study.

The Current Landscape of Neurosurgical Oncology in Low-Middle-Income Countries (LMIC): Strategies for the Path Forward.

OBJECTIVE: To promote global equity in research, innovation, and care, sharing knowledge and grasping current benchmarks is crucial. Despite LIC/LMIC constituting around 80% of the global population, their contribution to neurosurgery research is less than 5%. This study aims to assess the status of neurosurgical oncology in LIC/LMIC using published data, offering strategic insights for progress. METHODS: Conducting a retrospective bibliometric analysis via PubMed and Scopus databases, we documented reports published (2015-2021) by neurosurgical department-affiliated investigators in LICs/LMICs. World Bank classifications identified LIC and LMIC. Reviewed papers underwent further scrutiny based on independent and associated keyword lists. RESULTS: Our systematic approach revealed 189 studies from LMIC in 10 neurosurgery journals. Of these, 53% were case reports, with 88% focusing on brain pathologies and 12% on the spine. Intra-axial brain tumors (45.8%), extra-axial/skull base (38.4%), and metastasis (3.68%) were prominent. Among noncase report publications, surgical technique and outcome were common themes. India, Egypt, and Tunisia led in publications, with 94% appearing in journals with an impact factor below 5. No papers originated from LIC. CONCLUSIONS: This study reinforces existing findings that data from LMIC inadequately represent their populations, impeding a comprehensive understanding of their neurosurgical oncology landscape. Language barriers and data collection difficulties contribute to this gap. Addressing these challenges could significantly enhance progress in shaping the future of neurosurgical oncology in these regions.

Predictive Factors of Long-Term Neurologic Outcome and Progression-Free Survival in Intramedullary Spinal Cord Tumors: A 10-year Single-Center Cohort Study and Review of the Literature.

BACKGROUND: Intramedullary spinal cord tumors (IMSCTs) are a rare subgroup of neoplasms, encompassing both benign, slow-growing masses, and malignant lesions; radical surgical excision represents the cornerstone of treatment for such pathologies regardless of histopathology, which, on the other hand, is a known predictor of survival and neurologic outcome postsurgery. The present study aims to investigate the relevance of other factors in predicting survival and long-term functional outcomes. METHODS: We conducted a review of current literature on functional outcomes of IMSCTs, as well as a 10-years prospective analysis of a wide cohort of patients with diagnosis of IMSCTs who underwent surgical resection at our institution. RESULTS: Our series encompasses 60 patients with IMSCTS, among which 36 ependymomas, 6 cavernous angiomas, 5 hemangioblastomas, 6 WHO Grade I-IV astrocytomas, 3 intramedullary spinal metastases and 4 miscellaneous tumors. GTR was achieved in 76,67% of patients, with high preoperative McCormick grade, syringomyelia and changes at neurophysiologic monitoring being the strongest predictors at multivariate analysis (P = 0.0027, P = 0.0017 and P = 0.001 respectively). CONCLUSIONS: Consistently with literature, preoperative neurologic function is the most important factor predicting long-term functional outcome (0.17, CI 0.069-0.57 with P = 0.0018), advocating for early surgery in the management of IMSCTs, whereas late complications such as myelopathy and neuropathic pain were present regardless of preoperative function.

A novel somatostatin receptor ligand for human ACTH - and GH -secreting pituitary adenomas.

OBJECTIVE: Somatostatin receptor ligands have come to play a pivotal role in the treatment of both ACTH- and GH-secreting pituitary adenomas. Clinical efficacy averages 30-50%, thus a considerable number of patients with Cushing's disease or acromegaly remain unresponsive to this therapeutic approach. HTL0030310 is a new somatostatin receptor ligand selective for subtype 5 over subtype 2, thus with a different receptor profile compared to clinical somatostatin receptor ligands. DESIGN: Assessment of the effect of HTL0030310 on hormone secretion in human ACTH- and GH-secreting pituitary adenomas in vitro. METHODS: Primary cultures from 3 ACTH-secreting and 5 GH-secreting pituitary adenomas were treated with 1, 10 and 100 nM HTL0030310 alone or with 10 nM CRH or GHRH, respectively. Parallel incubations with 10 nM pasireotide were also carried out. ACTH and GH secretion were assessed after 4 and 24 hour incubation; SSTR2, SSTR3, SSTR5, GH and POMC expression were evaluated after 24 hours. RESULTS: HTL0030310 reduced unchallenged ACTH and POMC levels up to 50% in 2 ACTH-secreting adenomas and blunted CRH-stimulated ACTH/POMC by 20-70% in all 3 specimens. A reduction in spontaneous GH secretion was observed in 4 GH-secreting adenomas and in 2 specimens during GHRH co-incubation. SSTRs expression was detected in all specimens. CONCLUSIONS: This first study on a novel somatostatin receptor 5-preferring ligand indicates that HTL0030310 can inhibit hormonal secretion in human ACTH- and GH-secreting pituitary adenomas. These findings suggest a potential new avenue for somatostatin ligands in the treatment of Cushing's disease and acromegaly.

Predicting outcomes following cognitive behaviour therapy in child anxiety disorders: the influence of genetic, demographic and clinical information.

BACKGROUND: Within a therapeutic gene by environment (G × E) framework, we recently demonstrated that variation in the Serotonin Transporter Promoter Polymorphism; 5HTTLPR and marker rs6330 in Nerve Growth Factor gene; NGF is associated with poorer outcomes following cognitive behaviour therapy (CBT) for child anxiety disorders. The aim of this study was to explore one potential means of extending the translational reach of G × E data in a way that may be clinically informative. We describe a 'risk-index' approach combining genetic, demographic and clinical data and test its ability to predict diagnostic outcome following CBT in anxious children. METHOD: DNA and clinical data were collected from 384 children with a primary anxiety disorder undergoing CBT. We tested our risk model in five cross-validation training sets. RESULTS: In predicting treatment outcome, six variables had a minimum mean beta value of 0.5:5HTTLPR, NGF rs6330, gender, primary anxiety severity, comorbid mood disorder and comorbid externalising disorder. A risk index (range 0-8) constructed from these variables had moderate a predictive ability (AUC = .62-.69) in this study. Children scoring high on this index (5-8) were approximately three times as likely to retain their primary anxiety disorder at follow-up as compared with those children scoring 2 or less. CONCLUSION: Significant genetic, demographic and clinical predictors of outcome following CBT for anxiety-disordered children were identified. Combining these predictors within a risk index could be used to identify which children are less likely to be diagnosis-free following CBT alone and require longer or enhanced treatment. The 'risk-index' approach represents one means of harnessing the translational potential of G × E data.

Tuberculum sellae meningiomas: surgical outcomes in 65 patients, review of the literature and proposal for an anatomical and radiological classification.

Tuberculum sellae meningiomas (TSM) are challenging tumors due to their proximity to vital neurovascular structures. We propose a new classification system based on anatomical and radiological parameters. All patients treated for TSM, between January 2003 and December 2016, have been retrospectively reviewed. A systematic research was performed in PubMed database to review all studies comparing the performance of transcranial (TCA) and transphenoidal (ETSA) approaches. Overall, 65 patients were included in the surgical series. Gross total removal (GTR) was achieved in 55 patients (85%) and near total resection in 10 (15%). 54 patients (83%) showed a stability or an improvement of visual functions and 11 (17%) worsened. Postoperative complications were observed in seven patients (11%): CSF leak in one patient (1.5%); diabetes insipidus in two (3%); hypopituitarism in two (3%) third cranial nerve paresis and subdural empyema in one (1.5%). For the literature review, data about 10,833 patients (TCA N.=9159; ETSA N.=1674) were recorded; GTR was achieved in 84.1% (range 68-92%) of TCA and in 79.1% (range 60-92%) of ETSA; visual improvement (VI) occurred in 59.3% of TCA (range 25-84%) and in 79.3% of ETSA (range 46-100%); visual deterioration (VD) was registered in 12.7% of TCA (0-24%) and in 4.1% of ETSA (range 0-17%); a CSF-leak was observed in 3.8% of TCA (range 0-8%) while in ETSA in 18.6% of patients (range 0-62%); vascular injuries was reported in 4% (range 0-15%) of TCA and in 1.5% (range 0-5%) of ETSA. In conclusion, TSMs represent a unique category of midline tumors. The proposed classification system provides an intuitive and reproducible method in the choice of the most suitable approach.