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OBJECTIVE Due to their deep and medial location, range of seizure semiologies, and poor localization on ictal electroencephalography (EEG), cingulate gyrus seizures can be difficult to diagnose and treat. The aim of this study was to review the available evidence on postoperative outcomes after cingulate epilepsy surgery. METHODS A comprehensive literature search of the PubMed/MEDLINE, Ovid Embase, Ovid Scopus, and Cochrane Library databases was conducted to identify studies that investigated postoperative outcomes of patients with cingulate epilepsy. Seizure freedom at the last follow-up (at least 12 months) was the primary endpoint. The literature search was supplemented by the authors’ institutional series (4 patients). RESULTS Twenty-one studies were identified, yielding a total of 105 patients (68 with lesional epilepsy [65%]). Median age at surgery was 23 years, and 56% of patients were male. Median epilepsy duration was 7.5 years. Invasive EEG recording was performed on 69% of patients (53% of patients with lesional epilepsy and 97% of those with nonlesional epilepsy, p < 0.001). The most commonly resected region was the anterior cingulate (55%), followed by the posterior (17%) and middle (14%) cingulate. Lesionectomy alone was performed in 9% of patients. Additional extracingulate treatment was performed in 54% of patients (53% of patients with lesional epilepsy vs 57% of those with nonlesional epilepsy, p = 0.87). The most common pathology was cortical dysplasia (54%), followed by low-grade neoplasm (29%) and gliosis (8%). Seizure freedom was noted in 72% of patients (median follow-up 24 months). A neurological deficit was noted in 27% of patients (24% had temporary deficit), with the most common deficit being motor weakness (13%) followed by supplementary motor area syndrome (9.5%). Univariate survival analysis revealed significantly greater probability of seizure freedom in patients with lesional epilepsy (p = 0.015, log-rank test). CONCLUSIONS Surgical treatment of drug-resistant focal epilepsy originating from the cingulate gyrus is safe, leads to low rates of permanent adverse effects, and leads to high rates of long-term seizure freedom in carefully selected patients. These data may serve as a benchmark for surgical counseling of patients with cingulate epilepsy.

Background Jugular paragangliomas represent a surgical challenge due to their vascularity and proximity to vital neurovascular structures. Preoperative embolization aids in reducing intraoperative blood loss, transfusion requirements, and improves surgical visualization. Several embolization agents have been used. Objective The aim of this study is to evaluate the safety and efficacy of PVA in pre-operative embolization of jugular paragangliomas. Methods A retrospective review of all patients who underwent jugular paraganglioma resection with pre-operative embolization between 2000 and 2020 was performed. Pre-operative data including baseline patient and tumor characteristics were documented. Outcomes of preoperative embolization including extent of devascularization and post-embolization complications were recorded. Early and long-term postoperative outcomes were reported. Results Twenty-nine patients met study criteria with a median age of 38 years. Average tumor size was 3.4±1.8 cm. The most commonly encountered arterial feeder was the ascending pharyngeal artery followed by the posterior auricular artery. More than 50% reduction in tumor blush was achieved in 25 patients (86.2%). None of the patients experienced new or worsening cranial neuropathy following embolization. Gross total or Near total resection was achieved in 13 patients (44.8%). A STR or NTR was chosen in these patients to preserve cranial nerve function or large vessel integrity. Average intraoperative estimated blood loss was 888 ml, 9 patients (31%) required intra-operative transfusion of blood products. Extent of resection and post-operative complications did not correlate with extent of devascularization. Conclusion Pre-operative embolization of jugular paraganglioma tumors with PVA particles is an effective strategy with a high safety profile.

OBJECTIVE The prevalence of epilepsy in the older adult population is increasing. While surgical intervention in younger patients is supported by level I evidence, the safety and efficacy of epilepsy surgery in older individuals is less well established. The aim of this study was to evaluate seizure freedom rates and surgical outcomes in older epilepsy patients. METHODS The authors’ institutional electronic database was queried for patients older than 50 who had undergone epilepsy surgery during 2002–2018. Cases were grouped into 50–59, 60–69, and 70+ years old. Seizure freedom at the last follow-up constituted the primary outcome of interest. The institutional analysis was supplemented by a literature review and meta-analysis (random effects model) of all published studies on this topic as well as by an analysis of complication rates, mortality rates, and cost data from a nationwide administrative database (Vizient Inc., years 2016–2019). RESULTS A total of 73 patients (n = 16 for 50–59 years, n = 47 for 60–69, and n = 10 for 70+) were treated at the authors’ institution. The median age was 63 years, and 66% of the patients were female. At a median follow-up of 24 months, seizure freedom was 73% for the overall cohort, 63% for the 50–59 group, 77% for the 60–69 group, and 70% for the 70+ group. The literature search identified 15 additional retrospective studies (474 cases). Temporal lobectomy was the most commonly performed procedure (73%), and mesial temporal sclerosis was the most common pathology (52%), followed by nonspecific gliosis (19%). The pooled mean follow-up was 39 months (range 6–114.8 months) with a pooled seizure freedom rate of 65% (95% CI 59%–72%). On multivariable meta-regression analysis, an older mean age at surgery (coefficient [coeff] 2.1, 95% CI 1.1–3.1, p < 0.001) and the presence of mesial temporal sclerosis (coeff 0.3, 95% CI 0.1–0.6, p = 0.015) were the most important predictors of seizure freedom. Finally, analysis of the Vizient database revealed mortality rates of 0.5%, 1.1%, and 9.6%; complication rates of 7.1%, 10.1%, and 17.3%; and mean hospital costs of $31,977, $34,586, and $40,153 for patients aged 50–59, 60–69, and 70+ years, respectively. CONCLUSIONS While seizure-free outcomes of epilepsy surgery are excellent, there is an expected increase in morbidity and mortality with increasing age. Findings in this study on the safety and efficacy of epilepsy surgery in the older population may serve as a useful guide during preoperative decision-making and patient counseling.

OBJECTIVE Pituitary adenoma is one of the most common primary intracranial neoplasms. Most of these tumors are soft, but up to 17% may have a firmer consistency. Therefore, knowing the tumor consistency in the preoperative setting could be helpful. Multiple imaging methods have been proposed to predict tumor consistency, but the results are controversial. This study aimed to evaluate the efficacy of MR elastography (MRE) in predicting tumor consistency and its potential use in a series of patients with pituitary adenomas. METHODS Thirty-eight patients with pituitary adenomas (≥ 2.5 cm) were prospectively evaluated with MRI and MRE before surgery. Absolute MRE stiffness values and relative MRE stiffness ratios, as well as the relative ratio of T1 signal, T2 signal, and diffusion-weighted imaging apparent diffusion coefficient (ADC) values were determined prospectively by calculating the ratio of those values in the tumor to adjacent left temporal white matter. Tumors were classified into three groups according to surgical consistency (soft, intermediate, and firm). Statistical analysis was used to identify the predictive value of the different radiological parameters in determining pituitary adenoma consistency. RESULTS The authors included 32 (84.21%) nonfunctional and 6 (15.79%) functional adenomas. The mean maximum tumor diameter was 3.7 cm, and the mean preoperative tumor volume was 16.4 cm3. Cavernous sinus invasion was present in 20 patients (52.63%). A gross-total resection was possible in 9 (23.68%) patients. The entire cohort’s mean absolute tumor stiffness value was 1.8 kPa (range 1.1–3.7 kPa), whereas the mean tumor stiffness ratio was 0.66 (range 0.37–1.6). Intraoperative tumor consistency was significantly correlated with absolute and relative tumor stiffness (p = 0.0087 and 0.007, respectively). Tumor consistency alone was not a significant factor for predicting gross-total resection. Patients with intermediate and firm tumors had more complications compared to patients with soft tumors (50.00% vs 12.50%, p = 0.02) and also had longer operative times (p = 0.0002). CONCLUSIONS Whereas other MRI sequences have proven to be unreliable in determining tumor consistency, MRE has been shown to be a reliable tool for predicting adenoma consistency. Preoperative knowledge of tumor consistency could be potentially useful for surgical planning, counseling about potential surgical risks, and estimating the length of operative time.

Objective To discuss optimal treatment strategy for spindle cell oncocytoma (SCO) of the pituitary gland. Methods Institutional cases were retrospectively reviewed. A systematic literature search and subsequent quantitative synthesis were performed for further analysis. The detailed features were summarized and the tumor control rate (TCR) was calculated. Results Eighty-five patients (6 institutional and 79 literature) were included. The annual incidence was approximately 0.01–0.03/100,000. The mean age was 56 years. Vision loss was present in 60%. Seventy-three percent showed hormonal abnormalities. On magnetic resonance imaging, tumor was avidly enhancing, and the normal gland was commonly displaced anterosuperiorly. Evidence of hypervascularity was seen in 77%. Gross total resection (GTR) was achieved in only 24% because of its hypervascular, fibrous, and adhesive nature. The mean postoperative follow-up was 3.3 years for institutional cases and 2.3 years for the integrated cohort. The TCR was significantly better after GTR (5-year TCR, 75%; P = 0.012) and marginally better after non-GTR + upfront radiotherapy (5-year TCR, 76%; P = 0.103) than after non-GTR alone (5-year TCR, 24%). The TCRs for those with low Ki-67 index (≤5%) were marginally better than those with higher Ki-67 index (5-year rate, 57% vs. 23%; P = 0.110). Conclusions Frequent endocrine-related symptoms, hypervascular signs, and anterosuperior displacement of the gland support preoperative diagnosis of SCO. GTR seems to have better long-term tumor control, whereas the fibrous, hypervascular, and adhesive nature of SCO makes it difficult to achieve GTR. In patients with non-GTR, radiotherapy may help decrease tumor progression.

SUMMARY: Vascular venous malformations of the cavernous sinus have multiple imaging features that can be used to distinguish them from other entities in the region. Accurate identification of these lesions is essential: Vascular venous malformation lesions carry considerable risk of intraoperative hemorrhage, so preoperative recognition of vascular venous malformations can greatly impact the treatment strategies used. Nevertheless, because of their scarcity, many radiologists are unfamiliar with the radiologic and clinical features of cavernous sinus vascular venous malformations. This article will describe a case of an asymptomatic vascular venous malformation; outline its imaging, clinical, and pathologic features; and review the relevant literature regarding this diagnosis.

Menstrual cyclicity is a marker of health for reproductively mature women. Absent menses, or amenorrhea, is often the initial sign of pregnancy—an indication that the system is functioning appropriately and capable of generating the intended evolutionary outcome. Perturbations of menstrual regularity in the absence of pregnancy provide a marker for physiological or pathological disruption of this well-orchestrated process. New-onset amenorrhea with duration of 3 to 6 months should be promptly evaluated. Secondary amenorrhea can reflect structural or functional disturbances occurring from higher centers in the hypothalamus to the pituitary, the ovary, and finally, the uterus. Amenorrhea can also be a manifestation of systemic disorders resulting in compensatory inhibition of reproduction. Identifying the point of the breakdown is essential to restoring reproductive homeostasis to maintain future fertility and reestablish reproductive hormonal integrity. Among the most challenging disorders contributing to secondary amenorrhea is primary ovarian insufficiency (POI). This diagnosis stems from a number of possible etiologies, including autoimmune, genetic, metabolic, toxic, iatrogenic, and idiopathic, each with associated conditions and attendant medical concerns. The dual assaults of unanticipated compromised fertility concurrently with depletion of the normal reproductive hormonal milieu yield multiple management challenges. Fertility restoration is an area of active research, while optimal management of estrogen deficiency symptoms and the anticipated preventive benefits of hormone replacement for bone, cardiovascular, and neurocognitive health remain understudied. The state of the evidence for an optimal, individualized, clinical management approach to women with POI is discussed along with priorities for additional research in this population.

There is a clinical equipoise between burr hole drainage (BHD) or twist drill craniotomy (TDC) as initial surgical intervention in patients with chronic subdural hematoma (cSDH). Moreover, the impact of type of postoperative drainage is not well elucidated. We performed a systematic review and meta-analysis comparing outcomes following BHD and TDC for initial surgical management in cSDH and to understand the impact of negative suction drainage with TDC. A literature search was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for studies that directly compared TDC and BHD. The following outcomes were compared between TDC and BHD: mortality, recurrence, reoperations, complications, and cure rates. Subgroup analysis was performed to determine impact of negative suction drainage with TDC. Sixteen articles (n = 1,235; TDC: 663; BHD: 591) met inclusion criteria. Although complications (OR: 0.68, 95% CI: 0.38–1.23, p = 0.21; I2 = 31%), recurrence (OR: 1.16, 95% CI: 0.84–1.62, p = 0.37; I2 = 28%), cure (OR: 1.11, 95% CI: 0.72–1.72, p = 0.64, I2 = 34%), and mortality rates (OR: 1.20, 95% CI: 0.60–2.41; p = 0.61; I2 = 0%) were not significantly different between the two groups, TDC was associated with a higher reoperations than BHD (OR: 1.48, 95% CI:1.01–2.16, p = 0.04; I2 = 41%). Subgroup analysis demonstrated that TDC with negative suction drainage conferred equivalent reoperation rates as BHD (OR: 0.75, 95% CI: 0.24–2.35; p = 0.62; I2 = 65%); however, TDC without negative suction was associated with higher reoperations (OR: 1.62, 95% CI: 1.08–2.42; p = 0.02; I2 = 40%). A systematic review and meta-analysis of available literature directly comparing TDC and BHD for primary evacuation of cSDH did not demonstrate clear superiority of either technique, although reoperations may be higher following TDC. Use of negative suction drainage with TDC may lead to similar rates of reoperation as BHD.

PURPOSE In Prolactinomas, surgery or radiation are reserved for DA failure due to tumor resistance, intolerance to medication-induced side-effects, or patient preference. This systematic review and meta-analysis summarizes the currently available literature regarding the effectiveness of surgery to treat prolactinomas in patients who have failed DA therapy. METHOD A literature search was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for studies that reported outcomes of medically resistant and intolerant prolactinoma treated surgically. RESULTS 10 articles (Total N = 816, Surgery N = 657) met the inclusion criteria. 38% of patients who underwent surgery following DA failure achieved remission without need for further treatment (p

Objective Primary resection of adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma has become a front-line standard-of-care treatment for Cushing disease. However, surgical intervention can be challenging because of elevated blood pressure, as well as direct cortisol impacts on endothelial cells, vascular permeability, and tissue friability—potentially resulting in increased intraoperative bleeding. Tranexamic acid (TXA) is a well-studied, widely used intravenous hemostatic; however, the potential benefit during resection of ACTH-secreting pituitary adenoma is unstudied. The purpose of this study was to define an institutional protocol for perioperative administration of TXA in patients undergoing endoscopic endonasal approach for resection of ACTH-secreting pituitary adenoma, and to study the implementation of our novel protocol in a prospective fashion. Methods Criteria for preoperative TXA were defined by age, medical history, and risk factors. Descriptive statistics were reported for all patients receiving perioperative TXA. Results Thirty patients met inclusion criteria and underwent perioperative administration of TXA, using a standardized dosing protocol of a 10 mg/kg bolus in 30 minutes prior to incision, followed by maintenance infusion of 2 mg/kg/hour for the duration of the procedure. No incidence of myocardial infarction or postoperative thromboembolic events were noted. Subjective assessments indicated satisfaction with the patient selection protocol, and meaningful reduction in the extent of intraoperative bleeding. Conclusions Perioperative TXA represents a potentially efficacious approach for control of intraoperative bleeding during endonasal resection of ACTH-secreting tumors. Careful preoperative patient selection is emphasized, given the potential for thromboembolic complications; however, initial experience with our institutional protocol suggests a favorable risk/benefit profile when this treatment is applied judiciously.

Background The Food and Drug Administration approved the deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) as an adjunctive therapy for drug-resistant epilepsy (DRE) in the United States in 2018. The DBS Therapy for Epilepsy Post-Approval Study is further evaluating the safety and effectiveness of ANT-DBS among different patients' groups. For this study, devices for vagus nerve stimulation (VNS) must be removed prior to enrolment. Objective To investigate the outcomes of concomitant ANT-DBS and VNS treatment for DRE. Methods A retrospective analysis was performed for 33 patients who underwent ANT-DBS using previous VNS to define distinct subgroups: standard ANT-DBS (9 subjects), ANT-DBS with functional VNS (12 subjects), and ANT-DBS with the VNS implantable pulse generator explanted or turned off at the time of the DBS (12 subjects). Effectiveness and safety data were analyzed across the whole population and among subgroups. Results A mean decrease in seizure frequency of 55% was observed after a mean follow-up of 25.5 mo. Approximately 67% of patients experienced ≥50% reduction in seizure frequency. Seizure reduction percentage was not significantly different among groups. Approximately 50% of subjects with no appreciable improvement and 75% of those who showed benefit after VNS (including improvement in seizure frequency, seizure severity, and seizure duration or quality of life) achieved a seizure reduction ≥50% after ANT-DBS surgery. There were no complications related to concomitant VNS and ANT-DBS. Conclusion ANT-DBS for DRE provides excellent results despite previous and ongoing VNS therapy. Removal of VNS does not appear to be necessary before ANT-DBS.

OBJECTIVE Despite the growing emphasis on healthcare costs, limited data address this aspect of care within the vestibular schwannoma (VS) literature. We sought to determine which strategy confers the lowest lifetime cost and greatest quality-adjusted life-years (QALYs) for patients with small- to medium-sized sporadic VS tumors. STUDY DESIGN A Markov model was created to determine the most cost-effective management algorithm. Tumor characteristics, magnetic resonance imaging surveillance schedule, treatment outcomes, and health-related quality of life values were derived from previously published data. Cost estimates were based on CMS Fee Schedule reimbursement rates. SETTING Economic Evaluation Service within the Kern Center for the Science of Healthcare Delivery. PATIENTS Patients diagnosed with small- to medium-sized sporadic VS. INTERVENTIONS Upfront microsurgery following diagnosis, upfront radiosurgery following diagnosis, observation with microsurgery reserved for observed tumor growth, and observation with radiosurgery reserved for observed tumor growth. RESULTS Across patient ages at time of diagnosis ranging from 18 to 70 years, observation with subsequent radiosurgery used for tumor growth was the most cost-effective management algorithm while upfront microsurgery was the least. When presented with a hypothetical 50-year-old patient, the strategy with the lowest lifetime cost and highest QALYs was observation with subsequent radiosurgery reserved for tumor growth ($32,161, 14.11 QALY), followed by observation with microsurgery reserved for tumor growth ($34,503, 13.94 QALY), upfront radiosurgery ($43,456, 14.02 QALY), and lastly, upfront microsurgery ($47,252, 13.60 QALY). Sensitivity analyses varying mortality rates, estimated costs, health-related quality of life, and progression to nonserviceable hearing demonstrated consistent ranking among treatments. CONCLUSIONS When considering initial management of small- and medium-sized sporadic VSs, neither lifetime cost nor QALYs support upfront microsurgery or radiosurgery, even for younger patients. Initial observation with serial imaging, reserving radiosurgery or microsurgery for patients exhibiting tumor growth, confers the greatest potential for optimized lifetime healthcare cost and QALY outcomes.

Aims Hip arthroplasty does not always restore normal anatomy. This is due to inaccurate surgery or lack of stem sizes. We evaluated the aptitude of four total hip arthroplasty systems to restore an anatomical and medialized hip rotation centre. Methods Using 3D templating software in 49 CT scans of non-deformed femora, we virtually implanted: 1) small uncemented calcar-guided stems with two offset options (Optimys, Mathys), 2) uncemented straight stems with two offset options (Summit, DePuy Synthes), 3) cemented undersized stems (Exeter philosophy) with three offset options (CPT, ZimmerBiomet), and 4) cemented line-to-line stems (Kerboul philosophy) with proportional offsets (Centris, Mathys). We measured the distance between the templated and the anatomical and 5 mm medialized hip rotation centre. Results Both rotation centres could be restored within 5 mm in 94% and 92% of cases, respectively. The cemented undersized stem performed best, combining freedom of stem positioning and a large offset range. The uncemented straight stem performed well because of its large and well-chosen offset range, and despite the need for cortical bone contact limiting stem positioning. The cemented line-to-line stem performed less well due to a small range of sizes and offsets. The uncemented calcar-guided stem performed worst, despite 24 sizes and a large and well-chosen offset range. This was attributed to the calcar curvature restricting the stem insertion depth along the femoral axis. Conclusion In the majority of non-deformed femora, leg length, offset, and anteversion can be restored accurately with non-modular stems during 3D templating. Failure to restore hip biomechanics is mostly due to surgical inaccuracy. Small calcar guided stems offer no advantage to restore hip biomechanics compared to more traditional designs. Cite this article: Bone Jt Open 2021;2(7):476–485.

BACKGROUND AND IMPORTANCE Progressive episodic spells of altered levels of consciousness, often advancing to include paroxysmal autonomic instability, may be indicative of a diencephalic dysfunction underlying spontaneous intracranial hypotension (SIH). A rare, and often indolent, etiology may be spinal cerebrospinal fluid (CSF) leak-an elusive diagnosis, especially in cases of CSF-venous fistula (CVF) that are often missed on routine computed tomography (CT) myelography and magnetic resonance imaging (MRI). CLINICAL PRESENTATION We report an unusual case of a 50-yr-old woman who presented with rapidly progressive cyclical, self-resolving episodes of altered mentation and decreased arousal later in the day. Scrutiny of serial brain MRIs led to a diagnosis of SIH, with severe downward diencephalic and brain stem displacement-resulting in cerebral aqueduct occlusion with obstructive hydrocephalus. Initial clinical improvement occurred with CSF diversion, but the patient quickly deteriorated-developing diencephalic spells, including extensor posturing and severely depressed levels of consciousness. Clinical improvement was seen with stopping CSF diversion and Trendelenburg-positioning. After intensive spinal imaging, dynamic CT myelography identified a left T10 nerve root diverticula and CSF-venous fistula. Surgical obliteration resulted in rapid, profound neurological improvement, and ultimately full neurological recovery by 1 yr. CONCLUSION In our patient, worsening episodes of confusion, postural headaches, and autonomic instability developed due to SIH, which induced profound downward displacement and compression of the diencephalon and brain stem, and accompanied by subsequent obstructive hydrocephalus. Diagnostic persistence identified the CVF, which had caused the complex multifold pathophysiology and clinical presentation. If suspicion remains high for CVF, persistent spinal imaging, particularly with dynamic myelography, may be crucial.

Background Gonadotroph pituitary adenoma (Gn-PA) may rarely cause ovarian hyperstimulation syndrome, leading to infertility in women, although this remains poorly described. Methods We present a quantitative systematic review including 2 patients from our institutional and 48 from the literature with Gn-PA causing ovarian hyperstimulation syndrome to thoroughly describe the clinical features and therapeutic outcomes from multidisciplinary aspects. Results The patients had a mean age of 31.5 years and a mean follicle-stimulating hormone level of 14.4 IU/L. Estradiol level was high in 82% of patients, at >350 pg/mL. The mean maximal adenoma diameter was 22 mm, with a Knosp grade ≥3 in 10 patients. Abdominal surgery preceded adenoma resection in 24 patients (48%). Among 25 patients for whom extent of resection was recorded, total adenoma resection was achieved in 12. Through a mean follow-up of 25 months, adenoma recurrence was observed in 5 patients, who were treated with re-resection (n = 2), radiation (n = 2), and medical therapy followed by bilateral oophorectomy (n = 1). Medical therapies were partially effective or ineffective, and adenoma shrinkage did not follow; gonadotropin-releasing hormone agonists/antagonists were partially effective in 20% of patients (2/10), dopamine agonists in 44% (8/18), and somatostatin analogues in 50% (1/2). Four experienced swelling of tumor/ovaries after gonadotropin-releasing hormone agonists/antagonists administration. Overall, chemical remission was obtained in 26 of 28 patients, normalization of ovaries in 25 of 27, and successful pregnancy in 12 of 14. Conclusions Adenoma resection is the main treatment, leading to reduction in ovarian size and biochemical remission, with a high likelihood of subsequent spontaneous pregnancy. Increased awareness of this rare condition may help avoid unnecessary abdominal procedures.

Objective The collision of pituitary adenoma and craniopharyngioma is extremely rare and thus there remains a paucity of data. Methods We described a patient from our institution. We also performed a systematic review and subsequent quantitative synthesis of the literature (n = 21) and our institutional case to yield an integrated cohort, and a descriptive analysis was carried out. Results Twenty-two patients (15 males and 7 females) were included in the integrated cohort. The median age was 47.0 years (range, 8–75 years). The tumor subtypes were 5 somatotropic, 5 lactotropic, 4 nonfunctioning, 3 gonadotropic, 2 corticotropic, 1 plurihormonal, and 1 silent subtype 3 for pituitary adenomas, and 19 adamantinomatous, 2 papillary, and 1 unknown subtype for craniopharyngiomas. Three different radiographic patterns were observed: solid mass with cystic component (n = 5), coexistence of two distinct solid components (n = 3), and a mixed-intensity solid mass (n = 5). The first 2 were consistent with histologically separate collision, whereas the third was consistent with histologically admixed collision. Among 19 patients in whom the postoperative course was recorded, a secondary intervention was required in 14 (73.7%) because of tumor progression or residual. The recurrence rate after gross total resection was 33.3%. Postoperative hormone replacement was required in 33.3%. The 10-year cumulative overall survival was 73.1%. Conclusions Most craniopharyngiomas were adamantinomatous. There are 2 types of collisions: separated and admixed. Tumor control, overall survival, and endocrinologic remission are more challenging to achieve than for solitary tumors, but gross total resection of both tumors is important for satisfactory tumor control.

To clarify the need for post-operative radiation treatment in skull base chondrosarcomas (SBCs). A retrospective analysis of patients with grade I or II SBC. Patients were divided according to post-surgical treatment strategies: (A) planned upfront radiotherapy and (B) watchful waiting. Tumor control and survival were compared between the treatment groups. The median follow-up after resection was 105 months (range, 9–376). Thirty-two patients (Grade 1, n = 16; Grade 2, n = 16) were included. The most frequent location was petroclival (21, 64%). A gross total resection (GTR) was achieved in 11 patients (34%). Fourteen (44%) underwent upfront radiotherapy (group A) whereas 18 (56%) were followed with serial MRI alone (group B). The tumor control rate for the entire group was 77% and 69% at 10- and 15-year, respectively. Upfront radiotherapy (P = 0.25), extent of resection (P = 0.11) or tumor grade (P = 0.83) did not affect tumor control. The majority of Group B patients with recurrent tumors (5/7) obtained tumor control with repeat resection (n = 2), salvage radiotherapy (n = 2), or a combination of both (n = 1). The 10-year disease-specific survival was 95% with no difference between the group A and B (P = 0.50). For patients with grade I/II SBC, a reasonable strategy is deferral of radiotherapy after maximum safe resection until tumor progression or recurrence. At that time, most patients can be successfully managed with salvage radiotherapy or surgery. Late recurrences may occur, and life-long follow-up is advisable.

We assessed extracranial contamination of the near-infrared spectroscopy (NIRS) signal during administration of phenylephrine. The study was performed with NIRO 200NX which employs both the Modified Beer-Lambert (MBL) method to measure total hemoglobin (tHb, expressed in µM), and Spatially Resolved Spectroscopy (SRS) to measure total hemoglobin content (nTHI, expressed in arbitrary units (a.u.)). SRS tends to not be affected by extracranial blood flow. As vasoconstriction with phenylephrine mainly occurs in the extracranial area, we hypothesized that if NIRS measurements are indeed prone to extracranial contamination, tHb will be more affected by the administration of phenylephrine than nTHI. After ethical committee approval, 20 consenting cardiac surgery patients were included. Phenylephrine was administered whenever clinically indicated and its effect on nTHI and tHb was evaluated. To adjust for the difference in raw scale units, Z-scores were calculated. Data were analyzed with Wilcoxon Signed Ranks Test and the Hodges-Lehmann method. A total of 191 data sets were obtained in 20 patients (10 male, 65 ± 15 years, 77 ± 16 kg, 166 ± 11 cm). The median difference before and after administration of phenylephrine was − 0.006 a.u. [95%CI − 0.010 to − 0.002] (p

Objectives Juvenile nasopharyngeal angiofibromas (JNAs) are uncommon tumors with an evolving treatment paradigm. The objective of this study was to compare our prior experience reported in 2005 with our most contemporary series to compare practice improvements and the impact of expanded endonasal procedures. Design Retrospective review comparing a contemporary 22 patients with JNA who underwent surgical management between 2005 and 2019, compared with a historical cohort of 65 patients from the same center. Results The most common presenting symptom was epistaxis (68%). The median maximum tumor diameter was 4.4 cm. All patients underwent preoperative embolization. An endoscopic endonasal approach (EEA) was used in 18 patients (82%), compared with 9% in the series prior to 2005. Gross total resection was achieved in all patients. The median estimated blood loss was 175 and 350 mL for EEA and open (transfacial) cases, respectively. Only two patients (9%) required a blood transfusion compared with 52% on the previous series. The median follow-up was 19 months. The overall recurrence rate was 9% in this series and 24% in the previous series. No patient required radiation therapy in follow-up compared with 3% in our historical cohort. Conclusion There have been significant changes regarding the management of patients with JNA compared with the previous Mayo Clinic experience. The EEA has become the preferred route over the transfacial approaches to treat JNA in selected patients who do not have intracranial extension. Preoperative embolization has aided in reducing the postoperative transfusion rates.

Resection of pituitary adenomas presents a number of unique challenges in neuro-oncology. The proximity of these lesions to key vascular and endocrine structures as well as the need to interpret neuronavigation in the context of shifting tumor position increases the complexity of the operation. More recently, substantial advances in fluorescence-guided surgery have been demonstrated to facilitate the identification of numerous tumor types and result in increased rates of complete resection and overall survival. A review of the literature was performed, and data regarding the mechanism of the fluorescence agents, their administration, and intraoperative tumor visualization were extracted. Both in vitro and in vivo studies were assessed. The application of these agents to pituitary tumors, their advantages and limitations, as well as future directions are presented here. Numerous laboratory and clinical studies have described the use of 5-ALA, fluorescein, indocyanine green, and OTL38 in pituitary lesions. All of these drugs have been demonstrated to accumulate in tumor cells. Several studies have reported the successful use of the majority of the agents in inducing intraoperative tumor fluorescence. However, their sensitivity and specificity varies across the literature and between functioning and non-functioning adenomas. At present, numerous studies have shown the feasibility and safety of these agents for pituitary adenomas. However, further research is needed to assess the applicability of fluorescence-guided surgery across different tumor subtypes as well as explore the relationship between their use and postoperative clinical outcomes.

The centromedian (CM) and anterior nucleus of the thalamus (ANT) are deep brain stimulation (DBS) targets for management of generalized, and focal drug resistant epilepsy (DRE), respectively. We report on a single center retrospective case series of 16 children and adults with DRE who underwent CM with simultaneous ANT (69 %) or CM without simultaneous ANT DBS (31 %). Seizure frequency, epilepsy severity, life satisfaction, and quality of sleep before and after DBS were compared. Baseline median seizure frequency was 323 seizures per month (IQR, 71-563 sz/mo). Median follow up time was 80 months (IQR 37-97 mo). Median seizure frequency reduction was 58 % (IQR 13-87 %, p = 0.002). Ten patients (63 %) reported ≥50 % seizure frequency reduction. Median seizure frequency reduction and responder rate were not significantly different for CM + ANT versus CM only. Seizure severity and life satisfaction were significantly improved. Three patients (19 %) developed device-related side effects, 2 of them (12.5 %) required surgical intervention. In a heterogenous population of children and adults with generalized, multifocal, posterior onset, and poorly localized DRE, CM with or without ANT DBS is feasible, relatively safe and is associated with reduced seizure frequency and severity, as well as improved life satisfaction.

Objective To address variance in clinical care surrounding sporadic vestibular schwannoma, a modified Delphi study was performed to establish a general framework to approach vestibular schwannoma care. A multidisciplinary panel of experts was established with deliberate representation from key stakeholder societies. External validity of the final statements was assessed through an online survey of registered attendees of the 8th Quadrennial International Conference on Vestibular Schwannoma. Study design Modified Delphi method. Methods The panel consisted of 16 vestibular schwannoma experts (8 neurotology and 8 neurosurgery) and included delegates representing the AAOHNSF, AANS/CNS tumor section, ISRS, and NASBS. The modified Delphi method encompassed a four-step process, comprised of one prevoting round to establish a list of focus areas and three subsequent voting rounds to successively refine individual statements and establish levels of consensus. Thresholds for achieving moderate consensus, at ≥67% agreement, and strong consensus, at ≥80% agreement, were determined a priori. All voting was performed anonymously via the Qualtrics online survey tool and full participation from all panel members was required before procession to the next voting round. Results Through the Delphi process, 103 items were developed encompassing hearing preservation (N = 49), tumor control and imaging surveillance (N = 20), preferred treatment (N = 24), operative considerations (N = 4), and complications (N = 6). As a result of item refinement, moderate (4%) or strong (96%) consensus was achieved in all 103 final statements. Seventy-nine conference registrants participated in the online survey to assess external validity. Among these survey respondents, moderate (N = 21, 20%) or strong (N = 73, 71%) consensus was achieved in 94 of 103 (91%) statements, and no consensus was reached in 9 (9%). Of the four items with moderate consensus by the expert panel, one had moderate consensus by the conference participants and three had no consensus. Conclusion This modified Delphi study on sporadic vestibular schwannoma codifies 100% consensus within a multidisciplinary expert panel and is further supported by 91% consensus among an external group of clinicians who regularly provide care for patients with vestibular schwannoma. These final 103 statements address clinically pragmatic items that have direct application to everyday patient care. This document is not intended to define standard of care or drive insurance reimbursement, but rather to provide a general framework to approach vestibular schwannoma care for providers and patients.

It is well established that unopposed estrogen, either endogenous or therapeutic, can induce endometrial hyperplasia and potentially endometrial cancer (EC). Anovulatory cycles, obesity, and insulin resistance are major risk factors for EC. Progestogen (progesterone and progestin), including levonorgestrel intrauterine device, are able to prevent or to treat hyperplasia, atypical hyperplasia, and even well-differentiated EC, as presented in this review. During menopausal hormone therapy, progestogens protect the endometrium against the proliferative effects of estrogens in women with a uterus. Whereas, recent epidemiologic data suggest that micronized progesterone (MP) is apparently safer for the breast, it could be less efficient than synthetic progestin on the endometrium. However, several studies from biopsies during treatment with MP do not show any increased risk of hyperplasia. Lack of compliance could explain the results on EC.

International audience; PurposeMost types of hereditary angioedema (HAE) are worsened by endogenous or exogenous estrogens. Conversely, androgens can improve HAE with abnormal C1-Inhibitor (C1-INH) by increasing C1-INH concentrations. Menopause is associated with an extinction of ovarian estrogenic and androgenic secretion. There is currently insufficient information on postmenopausal women with HAE. The objective of this study was to describe the activity of HAE in postmenopausal women.MethodsThis was a French retrospective, multicenter study in postmenopausal women with HAE with or without C1-INH deficiency/dysfunction. The patients were classified before and after menopause with a previously validated HAE disease severity score.ResultsWe included 65 women from 13 centers in France. The mean age was 62.7± 9.2 years, and the mean time between menopause and inclusion was 12.5± 9.1 years. HAE was associated with C1-INH deficiencyin 88% (n = 57) of the patients, a mutation of factor 12 in 8% (n = 5), a mutation in plasminogen gene in one, and unknown HAE for two. The HAE course was not different after menopause in 46.1% (n = 30), improved in 38.5% (n = 25), and worsened in 15.4% (n = 10). Improvement was correlated with estrogen sensitivity of angioedema before menopause (p = 0.06 for improvement vs no effect or worsening). In addition, we observed that only ten women received treatment (transdermal or oral estradiol+ progestogen) for their menopause symptoms. Among them, only 3 experienced worsening of symptoms (2 on transdermal and 1 on oral estradiol).ConclusionFollowing menopause, most women with HAE remain stable but some worsen. Improvement was mainly observed in patients with previous estrogen sensitivity. More research is required in menopausal women with HAE to better understand how to manage climacteric symptoms.

Growth hormone-producing pituitary adenomas are divided into two clinically relevant histologic subtypes, densely (DG-A) and sparsely (SG-A) granulated. Histologic subtype was evaluated in a large cohort of patients with acromegaly, separating DG-A and SG-A, and correlated with clinicopathological characteristics. Patients with acromegaly undergoing surgery as initial therapy between 1995 and 2015 were identified. Histologic subtype was determined by keratin expression pattern with CAM5.2 and correlated with clinical and imaging parameters, somatostatin receptor subtype 2 (SST2) expression, post-surgical remission rate, and application of a prognostic scoring system incorporating proliferation and invasiveness. One hundred thirty-one patients were included. Tumors were classified as DG-A (75, 57.3%), SG-A (29, 22.1%), intermediate (I-A) (9, 6.9%), and unclassified (18, 13.7%) when CAM5.2 was negative. DG-A and I-A were combined for analysis (DG/I-A) and compared to SG-A. Age, gender, proliferation, and post-surgical remission did not differ. SG-A were larger [2 vs. 1.5 cm (median), p = 0.03], more frequently invasive [65.5% vs. 32.9%, p = 0.004], associated with higher MRI T2-weighted signal ratio [1.01 vs. 0.82 (median), p = 0.01], showed lower SST2 expression (p

BackgroundTo address the reactivity and affinity against histidyl-transfer RNA synthetase (HisRS) autoantigen of anti-Jo1 autoantibodies from serum and bronchoalveolar lavage fluid (BALF) in patients with idiopathic inflammatory myopathies/anti-synthetase syndrome (IIM/ASSD). To investigate the associations between the reactivity profile and clinical data over time.MethodsSamples and clinical data were obtained from (i) 25 anti-Jo1+patients (19 sera with 16 longitudinal samples and 6 BALF/matching sera at diagnosis), (ii) 29 anti-Jo1−patients (25 sera and 4 BALF/matching sera at diagnosis), and (iii) 27 age/gender-matched healthy controls (24 sera and 3 BALF/matching sera). Reactivity towards HisRS full-length (HisRS-FL), three HisRS domains (WHEP, antigen binding domain (ABD), and catalytic domain (CD)), and the HisRS splice variant (SV) was tested. Anti-Jo1 IgG reactivity was evaluated by ELISA and western blot using IgG purified from serum by affinity chromatography. In paired serum-BALF, anti-Jo1 IgG and IgA reactivity was analyzed by ELISA. Autoantibody affinity was measured by surface plasmon resonance using IgG purified from sera. Correlations between autoantibody reactivity and clinical data were evaluated at diagnosis and longitudinally.ResultsAnti-Jo1 IgG from serum and BALF bound HisRS-FL, WHEP, and SV with high reactivity at the time of diagnosis and recognized both conformation-dependent and conformation-independent HisRS epitopes. Anti-HisRS-FL IgG displayed high affinity early in the disease. At the time of IIM/ASSD diagnosis, the highest autoantibody levels against HisRS-FL were found in patients ever developing interstitial lung disease (ILD) and arthritis, but with less skin involvement. Moreover, the reactivity of anti-WHEP IgG in BALF correlated with poor pulmonary function.Levels of autoantibodies against HisRS-FL, HisRS domains, and HisRS splice variant generally decreased over time. With some exceptions, longitudinal anti-HisRS-FL antibody levels changed in line with ILD activity.ConclusionHigh levels and high-affinity anti-Jo1 autoantibodies towards HisRS-FL were found early in disease in sera and BALF. In combination with the correlation of anti-HisRS-FL antibody levels with ILD and ILD activity in longitudinal samples as well as of anti-WHEP IgG in BALF with poor pulmonary function, this supports the previously raised hypothesis that the lung might have a role in the immune reaction in anti-Jo1-positive patients.

Cerebral amyloidomas, characterized by localized amyloid deposits in the nervous system in the absence of systemic disease, are rare. These typically consist of immunoglobulin light chain (AL)-type, predominantly lambda. Trigeminal nerve involvement is exceptionally rare with only 21 previously reported cases, three with bilateral disease. We report two additional cases of amyloid localized to Meckel’s cave with secondary involvement of the trigeminal nerves bilaterally, with protein characterization by mass spectrometry. The patients, both females, 39 and 49-years-old, respectively, presented with the insidious onset of progressive trigeminal neuropathy, including pain and numbness with sensory loss, refractory to medical therapy. One patient experienced bilateral symptoms. Magnetic resonance imaging demonstrated abnormal thickening and contrast enhancement along Meckel’s cave bilaterally in both cases. The clinical differential diagnosis included benign neoplasms and inflammatory disorders. At the time of biopsy, the trigeminal nerve was noted to be enlarged and multinodular in one case and associated with abnormal soft tan tissue in the other case. Microscopically, the nerve biopsies showed extensive Congo red-positive amyloid deposits. Liquid chromatography tandem mass spectrometry demonstrated that the amyloid was of (AL)-type in both cases (AL [kappa] in one case and AL [lambda] in the other). After extensive evaluation, there was no evidence of systemic involvement. Both patients received localized radiotherapy for their refractory symptoms. One patient has stable symptomatology and imaging. No follow-up is available for the other patient.

Objectives: Farm-level quantification of antimicrobial usage (AMU) in pig farms. Methods: In a cross-sectional study, AMU data on group treatments administered to a single batch of fattening pigs from birth to slaughter (group treatment data) and antimicrobials purchased during 1 year (purchase data) were collected at 180 pig farms in nine European countries. AMU was quantified using treatment incidence (TI) based on defined (DDDvet) and used (UDDvet) daily doses and defined (DCDvet) and used (UCDvet) course doses. Results: The majority of antimicrobial group treatments were administered to weaners (69.5% of total TIDDDvet) followed by sucklers (22.5% of total TIDDDvet). AMU varied considerably between farms with a median TIDDDvet of 9.2 and 7.1 for a standardized rearing period of 200 days based on group treatment and purchase data, respectively. In general, UDDvet and UCDvet were higher than DDDvet and DCDvet, respectively, suggesting that either the defined doses were set too low or that group treatments were often dosed too high and/or administered for too long. Extended-spectrum penicillins (31.2%) and polymyxins (24.7%) were the active substances most often used in group treatments, with the majority administered through feed or water (82%). Higher AMU at a young age was associated with higher use in older pigs. Conclusions: Collecting farm-level AMU data of good quality is challenging and results differ based on how data are collected (group treatment data versus purchase data) and reported (defined versus used daily and course doses).

Case and Principles of Management The case of a symptomatic, postmenopausal woman is presented and a full discussion of the approach to her management is discussed. Pertinent guidelines and scientific evidence are emphasized as support for the recommendations.

Objective Among combined oral contraception (COC) users, to determine the effect on ovarian activity and ovulation of waiting five days before restarting COC, versus restarting immediately, having taken ulipristal acetate 30 mg (UPA, the dose used for emergency contraception) after missing three consecutive COC pills. Study design Women already using COC were enrolled for two cycles of COC use (21/7 regimen). In cycle 2, all women omitted COC pills for three consecutive days (days 5,6,7), and on day 8 took UPA 30 mg. They were randomized either to restart their COC pills that same day (immediate restart) or to wait five days (delayed restart). Transvaginal ultrasound, and blood sampling for estradiol and progesterone were undertaken on days 4,8,11,13,15,18,22 and 26. A modified Hoogland score was used to quantify ovarian activity/ovulation and to assess whether luteal phase progesterone concentrations were sufficiently ‘adequate’ to have conferred a theoretical risk of pregnancy. Results No one ovulated with risk of pregnancy during the five days following UPA. Among 26 women with immediate restart, none ovulated with a theoretical risk of pregnancy at any time in the cycle. Four of 23 women (17.4% CI [5.0; 38.8]) with delayed restart ovulated with theoretical risk of pregnancy before the end of the cycle. This difference was statistically significant (p = 0.042). Conclusion Women who delay restarting COC for five days after taking UPA 30 mg are at much greater risk of ovulation, and therefore theoretically of pregnancy, than if they restart their COC on the same day as taking UPA. Current recommendations should be revisited. Implications Women who take UPA-EC after having missed combined oral contraceptive pills are advised to wait five days before restarting the COC. This delay puts them at risk of ovulation and, if intercourse occurs, theoretically therefore of pregnancy. Women who restart their COC pills immediately are much less likely to ovulate. The label for UPA-EC and clinical guidelines on using EC after missed pills should be revisited.

WHO grades II (atypical) and III (malignant) meningiomas are associated with significant morbidity and mortality. The role of adjuvant radiotherapy (RT) in management remains controversial. The goal of this study was to evaluate the impact of adjuvant RT on 5-year survival in patients with atypical and malignant meningiomas. We secondarily aimed to assess contemporary practice patterns and the impact of sociodemographic factors on outcome. We queried the National Cancer Database for patients ≥ 18 years of age with cranial atypical or malignant meningiomas from 2010 through 2015 who underwent surgical resection with or without adjuvant radiotherapy. Subjects with unknown WHO grade or radiation status and those not receiving any surgical procedure were excluded from analysis. The study includes 7486 patients, 6788 with atypical and 698 with malignant meningiomas. Overall 5-year survival was 76.9% (95% CI 75.5–78.3%) and 43.3% (95% CI 38.8–48.2%) among patients with WHO grades II and III meningiomas, respectively. Adjuvant RT correlated with improved survival in a multivariable model in patients with grade II tumors (HR 0.78; p = 0.029) regardless of the extent of resection. Age (HR 2.33; p

OBJECTIVEMultiple endocrine neoplasia type 1 (MEN1) is a rare, autosomal-dominant tumor disorder characterized by the development of pituitary tumors and other endocrine neoplasms. Diagnosis is made clinically based on the development of 2 or more canonical lesions (parathyroid gland, anterior pituitary, and enteropancreatic tumors) or in family members of a patient with a clinical diagnosis of MEN1 and the occurrence of one of the MEN1-associated tumors. The goal of this study was to characterize pituitary tumors arising in the setting of MEN1 at a single institution. The probability of tumor progression and the likelihood of surgical intervention in patients with asymptomatic nonfunctional pituitary adenomas were also analyzed.METHODSA retrospective review of a prospectively maintained institutional database was performed for patients with MEN1 diagnosed from 1970 to 2017. Data included patient demographics, tumor characteristics, treatment strategies, and outcomes.RESULTSA review of the database identified 268 patients diagnosed with MEN1, of whom 158 (59%) were female. Among the 268 patients, 139 (51.8%) had pituitary adenomas. There was a higher prevalence in women than in men (65% vs 35%, p < 0.005). Functional adenomas (57%) were more common. Prolactin-secreting adenomas were the most common functional tumors. Macroadenomas were seen in 27% of patients and were more likely to be symptomatic and locally aggressive (p < 0.001). Forty-nine patients (35%) underwent transsphenoidal resection at some point during their disease course. In 52 patients who were initially observed with MEN1 asymptomatic nonfunctional adenomas, only 5 (10%) progressed to need surgery. In MEN1 patients, an initial parathyroid lesion is most likely followed in order by pituitary, pancreatic, adrenal, and, finally, rare carcinoid tumors.CONCLUSIONSAsymptomatic nonfunctional pituitary adenomas in patients with MEN1 may be followed safely with MRI. In this series, parathyroid tumors developed at the lowest median age of all cardinal tumors, and development of additional cardinal MEN1 lesions followed a predictable pattern. This pattern of disease progression could have significant implications for disease surveillance in clinical practice and may help to target clinical resources to the lesions most likely to develop next. This may aid with early detection and treatment and warrants further study.

The aim of this review is to summarize characteristic imaging findings of common skull base lesions. In addition, this study aims to review the literature regarding important and interesting new advancements in imaging of the anterior and central skull base. Imaging techniques including magnetic resonance elastography, indocyanine green fluorescence, Gallium-DOTATATE PET/CT, peptide receptor radionucleotide therapy, and 3D printing are being used to advance the care of patients with skull base pathology. Characteristic CT and MRI findings can be used to narrow the differential diagnosis and plan treatment for anterior and central skull base lesions. New imaging techniques show promise in improving the care of patients with skull base lesions.

Objective: Intracranial dural arteriovenous fistulas represent pathological connections between dural arteries and dural veins, dural sinuses or meningeal veins in the absence of an intervening capillary bed. They are thought to be acquired secondary to trauma, surgery, sinus thrombosis, venous hypertension or arterial dysplasia. Methods: A 66-year-old Asian female presented with subarachnoid hemorrhage secondary to ruptured 2-mm saccular aneurysm of the left middle cerebral artery associated with fusiform dilatation. It was successfully treated with endovascular coiling. A right frontal external ventricular drain was also placed to treat her hydrocephalus. On post-bleed day 10, she became acutely unresponsive with a fixed and dilated right pupil. Head CT was obtained and revealed an acute right subdural hematoma which was emergently evacuated. Results: No obvious bleeders were identified during surgery. Patient improved and repeat catheter angiography a week later showed a new dural arteriovenous fistula fed by the anterior falcine artery and the middle meningeal artery to a cortical vein draining into the superior sagittal sinus. Conclusion: We hope that the present report will raise awareness to treating physicians to be cognizant of this unusual complication in their differential diagnosis when treating patients with an EVD in place.

Objective The objective of this study is to describe the clinical presentation, tumor characteristics, natural history, and treatment patterns of sinonasal osteosarcoma. Methods Fourteen patients who had been treated for osteosarcoma of the nasal cavity and paranasal sinuses at a tertiary care center were reviewed. In addition, a systematic review of the literature for osteosarcoma of the sinonasal cavity was performed. Results In a systematic review, including 14 patients from the authors' institution, 53 total studies including 88 patients were assessed. Median follow-up was 18 months (interquartile range: 8–39 months). The most common presenting symptoms were facial mass or swelling (34%), and nasal obstruction (30%). The most common paranasal sinus involved by tumor was the maxillary sinus (64%), followed by the ethmoid sinuses (52%). The orbit (33%), dura (13%) and infratemporal fossa (10%) were the most common sites of local invasion. The majority of patients underwent surgery followed by adjuvant therapy (52.4%). Increasing age was associated with decreased overall survival rate (unit risk ratio [95% confidence interval (CI)] = 1.02 [1.003–1.043]; p = 0.0216) and T4 disease was associated with decreased disease-specific survival rate (hazard ratio [HR] = 2.87; p = 0.0495). The 2- and 5-year overall survival rates were 68 and 40%, respectively, while 2- and 5-year disease-specific survival rates were 71% and 44%, respectively. Conclusion Sinonasal osteosarcomas are uncommon tumors and can pose a significant therapeutic challenge. Increasing age and T4 disease are associated with worse prognosis. This disease usually warrants consultation by a multidisciplinary team and consideration of multimodality therapy.

Background Developments in frameless neuronavigation and tubular retractors hold the potential for minimizing iatrogenic injury to the overlying cortex and subcortical tracts, with improved access to the ventricular system. The objective of the present study was to evaluate the surgical outcomes after resection of third ventricular colloid cysts using an integrated neuronavigation and channel-based approach. Methods We performed a multicenter retrospective analysis of surgical Outcomes after surgical resection of third ventricular colloid cysts via a transtubular trans-sulcal approach. Results A total of 16 patients were included, with a mean age of 42 years (range, 23–62 years). The mean maximum diameter of cysts was 14 mm (range, 7–28 mm), and preoperative hydrocephalous was present in 12 patients (75%). Gross total resection was achieved in all 16 cases. Of the 12 patients, 4 (25%) had undergone septum pellucidotomy, in addition to cyst resection. No case had required conversion to open craniotomy. No perioperative mortalities occurred. Three patients (18.8%) had developed transient memory deficits, 1 of whom had also developed a pulmonary thromboembolism. The median length of hospital stay was 4 days (range, 2–18 days). All the patients reported resolution of preoperative symptoms at the 1-month follow-up examination. Only 1 patient (6.25%) had required insertion of a ventriculoperitoneal shunt. The median follow-up duration was 6.5 months (range, 3–24 months), and no recurrences were observed. Conclusion Use of a channel-based navigable retractor provided a minimal trans-sulcal approach to third ventricular colloid cysts with the benefit of bimanual surgical control in an air medium for definitive resection of third ventricular colloid cysts.

Objective To ascertain long-term hearing outcomes in patients with serviceable hearing following microsurgical resection of sporadic vestibular schwannoma (VS). Study design Retrospective cohort. Setting Tertiary academic referral center. Patients Forty-three adult subjects with unilateral sporadic VS who had serviceable hearing (American Academy of Otolaryngology-Head and Neck Surgery [AAO-HNS] class A or B) on initial postoperative audiogram following microsurgical resection between 2003 and 2016 with a minimum of two postoperative audiograms available for review. Intervention Surgical treatment with a retrosigmoid or middle cranial fossa approach. Main outcome measure Rate of maintaining serviceable hearing, as estimated using the Kaplan-Meier method, in accordance with the 1995 and 2012 AAO-HNS guidelines on reporting hearing outcomes. Results The median immediate postoperative pure-tone average (PTA) and word recognition score (WRS) were 31 dB and 95%, respectively. At last follow-up, the median PTA was 38 dB with a median change of 5 dB from initial postoperative audiogram, and the median WRS was 90% with a median change of 0% from initial postoperative audiogram. Eight patients developed non-serviceable hearing at a median of 4.1 years following microsurgical resection (interquartile range, 2.9-7.0). The median duration of hearing follow-up for the 35 patients who maintained serviceable hearing was 3.1 years (interquartile range, 2.2-7.5). Tumor control was achieved in 41 (95%) patients. The rate of maintaining serviceable hearing at 5 years was 81%. Conclusion Microsurgical resection provides excellent tumor control and durable long-term hearing in those with AAO-HNS class A or B hearing postoperatively. The paradigm of proactive microsurgical resection-when the tumor is small and hearing is good-hinges on the surgeon's ability to preserve residual hearing in a very high percentage of cases at or near preoperative hearing levels to maintain an advantage over conservative observation with regard to long-term hearing preservation.

Estrogen has been known for a long time to be a trigger on auto-immunity and may influence the course of lupus. Women experiencing systemic lupus are at high risk for premature ovarian insufficiency if using cyclophosphamide, of osteoporosis, arterial ischemic diseases and venous thrombosis at young age. In about 30% of them, an antiphospholipid/anticoagulant antibody can occur which is associated with very high risk of thrombosis. However, the severity of the disease may vary and some women with lupus could benefit from a menopausal hormone therapy (MHT). As a consequence, management of menopause symptoms needs to evaluate carefully the condition of the patient, her lupus history and cardiovascular risk. We will describe the effect of lupus on menopause, of menopause on lupus and report in detail the literature available on MHT and the risk of lupus or the risk of flares in women with lupus. Some other options than MHT for the management of climacteric symptoms will be discussed.

Most of breast cancers are hormonedependent. Hormone treatment (contraception and menopause hormone treatment) has a promoter effect on preexisting lesions: the increase in risk decreases after stopping treatment. Hormonal contraception increases modestly the risk in current users but the amplitude of the risk remains low up to 40 years when this increase is more significant due of the number of breast cancer occurring at that age. Pregnancy decreases the risk if at a young age but after 25 years may increase the risk. Combined menopause hormone treatment is associated to a greater risk than estrogens alone. Breast cancer associated with hormone treatment is estradiol receptor positive. There is an increase in the risk with duration. Combining the hormone treatment with an anti-estrogen could decrease the risk of breast cancer and help to keep the benefits of estrogens.

OBJECTIVES/HYPOTHESIS To review hearing preservation after microsurgical resection of sporadic vestibular schwannomas according to tumor size. STUDY DESIGN Retrospective cohort. METHODS Baseline, intraoperative, and postoperative patient and tumor characteristics were retrospectively collected for a cohort who underwent hearing preservation microsurgery. Serviceable hearing was defined by a pure tone average ≤50 dB and word recognition score ≥50%. RESULTS A total of 243 patients had serviceable hearing preoperatively. Fifty (21%) tumors were confined to the internal auditory canal, and the median tumor size was 16.2 mm (interquartile range [IQR] 11.3-23.2) for tumors with cerebellopontine angle extension. Serviceable hearing was maintained in 64% of patients with tumors confined to the internal auditory canal, 28% with cerebellopontine angle extension

Over time, photovoltaic (PV) systems become increasingly susceptible to faults. Early fault detection and identification not only limits power losses and increases the systems lifetime, but also prevents more serious consequences, such as risk of fire or electrical shock. Although several accurate fault diagnosis methods have been proposed in literature, most PV systems remain unmonitored as the installations are not equipped with the required sensors. In this work, we propose a fault diagnosis technique that does not require on-site sensors. Rather, weather satellite and inverter measurements are used as inputs for the proposed machine learning model. As no dedicated sensors are needed, our method is widely applicable and cost-effective. A temporal convolutional neural network is developed to accurately identify 6 common types of faults, based on the past 24 h of measurements. The proposed approach is tested extensively on a simulated PV system, taking into account multiple severities of each fault type, and reaches an accuracy of over 86%.

Dynamic computer tomography (CT) is an emerging modality to analyze in-vivo joint kinematics at the bone level, but it requires manual bone segmentation and, in some instances, landmark identification. The objective of this study is to present an automated workflow for the assessment of three-dimensional in vivo joint kinematics from dynamic musculoskeletal CT images. The proposed method relies on a multi-atlas, multi-label segmentation and landmark propagation framework to extract bony structures and detect anatomical landmarks on the CT dataset. The segmented structures serve as regions of interest for the subsequent motion estimation across the dynamic sequence. The landmarks are propagated across the dynamic sequence for the construction of bone embedded reference frames from which kinematic parameters are estimated. We applied our workflow on dynamic CT images obtained from 15 healthy subjects on two different joints: thumb base (n = 5) and knee (n = 10). The proposed method resulted in segmentation accuracies of 0.90 ± 0.01 for the thumb dataset and 0.94 ± 0.02 for the knee as measured by the Dice score coefficient. In terms of motion estimation, mean differences in cardan angles between the automated algorithm and manual segmentation, and landmark identification performed by an expert were below 1°. Intraclass correlation (ICC) between cardan angles from the algorithm and results from expert manual landmarks ranged from 0.72 to 0.99 for all joints across all axes. The proposed automated method resulted in reproducible and reliable measurements, enabling the assessment of joint kinematics using 4DCT in clinical routine.

Chronic brain recordings suggest that seizure risk is not uniform, but rather varies systematically relative to daily (circadian) and multiday (infradian) cycles. Here, one human and seven dogs with naturally occurring epilepsy had continuous intracranial EEG (median 298 days) using novel implantable sensing and stimulation devices. Two pet dogs and the human subject received concurrent thalamic deep brain stimulation (DBS) over multiple months. All subjects had circadian and infradian cycles in the rate of interictal epileptiform spikes (IES). There was seizure phase locking to circadian and infradian IES cycles in five and seven out of eight subjects, respectively. Thalamic DBS modified circadian (all 3 subjects) and infradian (analysis limited to the human participant) IES cycles. DBS modified seizure clustering and circadian phase locking in the human subject. Multiscale cycles in brain excitability and seizure risk are features of human and canine epilepsy and are modifiable by thalamic DBS.

There is a paucity of data to guide anterior nucleus of the thalamus (ANT) deep brain stimulation (DBS) with brain sensing. The clinical Medtronic Percept DBS device provides constrained brain sensing power within a frequency band (power-in-band [PIB]), recorded in 10-min averaged increments. Here, four patients with temporal lobe epilepsy were implanted with an investigational device providing full bandwidth chronic intracranial electroencephalogram (cEEG) from bilateral ANT and hippocampus (Hc). ANT PIB-based seizure detection was assessed. Detection parameters were cEEG PIB center frequency, bandwidth, and epoch duration. Performance was evaluated against epileptologist-confirmed Hc seizures, and assessed by area under the precision-recall curve (PR-AUC). Data included 99 days of cEEG, and 20, 278, 3, and 18 Hc seizures for Subjects 1-4. The best detector had 7-Hz center frequency, 5-Hz band width, and 10-s epoch duration (group PR-AUC = .90), with 75% sensitivity and .38 false alarms per day for Subject 1, and 100% and .0 for Subjects 3 and 4. Hc seizures in Subject 2 did not propagate to ANT. The relative change of ANT PIB was maximal ipsilateral to seizure onset for all detected seizures. Chronic ANT and Hc recordings provide direct guidance for ANT DBS with brain sensing.

ObjectiveElectrical deep brain stimulation (DBS) is an established treatment for patients with drug-resistant epilepsy. Sleep disorders are common in people with epilepsy, and DBS may actually further disturb normal sleep patterns and sleep quality. Novel devices capable of DBS and continuous intracranial EEG (iEEG) telemetry enable detailed assessments of therapy efficacy and tracking sleep related comorbidities. Here, we investigate the feasibility of automated sleep classification using continuous iEEG data recorded from Papez’s circuit in four patients with drug resistant mesial temporal lobe epilepsy using an investigational implantable sensing and stimulation device with electrodes implanted in bilateral hippocampus (HPC) and anterior nucleus of thalamus (ANT).ApproachThe iEEG recorded from HPC is used to classify sleep during concurent DBS targeting ANT. Simultaneous polysomnography and HPC sensing were used to train, validate and test an automated classifier for a range of ANT DBS frequencies: no stimulation, 2 Hz, 7 Hz, and high frequency (>100 Hz).Main resultsWe show that it is possible to build a patient specific automated sleep staging classifier using power in band features extracted from one HPC sensing channel. The patient specific classifiers performed well under all thalamic DBS frequencies with an average F1-score 0.894, and provided viable classification into awake and major sleep categories, rapid eye movement (REM) and non-REM. We retrospectively analyzed classification performance with gold-standard polysomnography annotations, and then prospectively deployed the classifier on chronic continuous iEEG data spanning multiple months to characterize sleep patterns in ambulatory patients living in their home environment.SignificanceThe ability to continuously track behavioral state and fully characterize sleep should prove useful for optimizing DBS for epilepsy and associated sleep, cognitive and mood comorbidities.

SUMMARY: Optic nerve choristomas are rare entities in which a developmental focus of histologically normal tissue is abnormally located within or along a segment of the optic nerve. Although benign, choristomas may demonstrate slow growth, ultimately resulting in visual field deficits due to compression of the adjacent nerve in the few cases reported in the anterior fossa. Choristomas may have cystic components, though this has not been described in such lesions along the optic nerve. Here, a predominantly cystic optic nerve choristoma is described, with radiologic features mimicking those of an anterior cranial fossa neurenteric cyst. The case highlights the radiology-pathology correlates of choristomas and reviews the surgical approach and management of patients with such lesions.