Sativex® (nabiximols) cannabinoid oromucosal spray in patients with resistant multiple sclerosis spasticity: the Belgian experience.

BACKGROUND: This retrospective study evaluates patient-reported outcomes in patients with multiple sclerosis (MS) spasticity who were treated with a cannabinoid oromucosal spray (Sativex®, USAN name: nabiximols) after not sufficiently responding to previous anti-spasticity medications. METHODS: Of 276 patients from eight centers in Belgium who began treatment prior to 31 December 2017, effectiveness assessment data were available for 238 patients during the test period of 4 to 8/12 weeks, and for smaller patient cohorts with continued treatment for 6/12 months. RESULTS: Mean 0-10 spasticity Numerical Rating Scale (NRS) scores improved from 8.1 at baseline to 5.2 (week 4), 4.6 (week 8) and 4.1 (week 12). Mean EuroQoL Visual Analogue Scale (EQ VAS) scores increased from 39 at baseline to 52 (week 4), 57 (week 8) and 59 (week 12). Mean NRS and EQ VAS scores remained in the same 12 weeks' range in patients with longer-term data. The average dose of cannabinoid oromucosal spray was 6 sprays/day. Most of the 93 out of 276 patients, with initial prescription (33.7%), who discontinued treatment by week 12 did so within the first 8 weeks, mainly due to lack of effectiveness. By week 12, 171 (74%) of the 230 effectiveness evaluable patients reported a clinically meaningful response, corresponding to ≥30% NRS improvement. The tolerability of cannabinoid oromucosal spray was consistent with its known safety profile. CONCLUSIONS: More than 60% of the patients with MS who started add-on treatment with cannabinoid oromucosal spray reported a clinically relevant symptomatic effect and continued treatment after 12 weeks.

Possible involvement of the RARRES2/CMKLR1-system in metabolic and reproductive parameters in Holstein dairy cows.

BACKGROUND: In dairy cows, the energy cost of milk yield results in a negative energy balance (EB) and body fat mobilization that impairs reproductive efficiency. Emerging evidence suggests that the novel adipokines, Retinoic acid receptor responder protein 2 (RARRES2), and its main receptor, Chemokine-like receptor 1 (CMKLR1) are involved in the regulation of metabolic and ovarian functions. So, we investigated in a first experiment the plasma RARRES2, and RARRES2 and CMKLR1 mRNA expression levels in subcutaneous adipose tissue (SAT) and granulosa cells (GC) at different times of body fat mobilization in dairy cows (4, 8, 20 and 44 weeks postpartum, wk. pp. for SAT and 8, 20 and 44 wk. pp. for GC). Then, in a second experiment we examined the effect of high (HE) and low energy (LE) diets on the RARRES2 system and its links with metabolic and reproductive parameters. METHODS: The first experiment included 9 animals fed with HE diet from 4 to 44 wk. pp. and the second one included animals fed either a HE diet (n = 8) or a LE diet (n = 8) from - 4 to 16 wk. peripartum. In both experiments, various metabolic and reproductive parameters were determined and associated with plasma RARRES2 as measured by bovine ELISA. RARRES2 and CMKLR1 mRNA expression levels were analyzed by RT-qPCR in SAT after biopsy and GC after aspiration of follicles. RESULTS: Plasma RARRES2 levels were higher at 4 wk. pp. as compared to 20 and 44 wk. pp. and they were positively correlated with body fat mobilization and milk yield. RARRES2 and CMKLR1 mRNA expression levels increased from 4 to 8 wk. pp. (fat mobilization, EB < 0) and remained unchanged at 20 and 44 wk. pp. (fat reconstitution, EB > 0) as compared to 4 wk. pp. in SAT. RARRES2 and CMKLR1 mRNA levels decreased from 8 to 44 wk. pp. in GC from small follicles. In the second experiment, plasma RARRES2 increased from - 4 to 8 wk. peripartum similarly in both LE and HE cows. In addition, the area under of plasma RARRES2 curve was highly negatively associated with the number of small follicles obtained in HE animals during the cycle before the first artificial insemination. In SAT of HE cows, RARRES2 mRNA expression decreased at 1 wk. pp. compared to - 4 and 16 wk. peripartum whereas opposite expression patterns were obtained for CMKLR1. Similar results were observed for CMKLR1 mRNA expression in LE cows while there was no variation in RARRES2 mRNA expression. Moreover, RARRES2 mRNA was higher expressed in LE than in HE cows at 1 wk. pp. CONCLUSIONS: The lactation-induced fat and energy mobilization influenced plasma RARRES2 profile and mRNA expression pattern of RARRES2 and CMKLR1 similarly in both SAT and GC. In addition, the energy content of the diet did not affect plasma RARRES2 but it altered RARRES2 mRNA expression in SAT and the area under the curve of plasma RARRES2 that was negatively associated to the number of small follicles in HE animals. Thus, RARRES2 could be a metabolic or ovarian signal involved in the interactions between metabolic and reproductive functions in dairy cows.

Prediction of discharge destination after traumatic brain injury in children using the head abbreviated injury scale.

INTRODUCTION: Traumatic brain injury (TBI) is a major public health problem, particularly in children. Prognostication of injury severity at the time of presentation is difficult. The Abbreviated Injury Scale (AIS) is a commonly used anatomical-based coding system created to classify and describe injury severity after initial presentation, once test results are able to better define the anatomical characteristics of the injury. We hypothesize that the Head AIS can predict discharge destination in children after TBI. METHODS: The trauma registry database for a Pediatric Level 1 Trauma center was queried for patients age ≤14 years from 2006 to 2015 with a Head AIS>2. All diagnoses with head AIS>2 were retrieved. Since one patient can have multiple diagnoses with an AIS>2, we selected the diagnosis with highest Head AIS associated with each patient. The demographics, length of stay, and the discharge disposition of patients were retrieved. Descriptive statistics were performed and association of Head AIS with the length of stay and discharge disposition was determined using logistic regression. RESULTS: 393 pediatric patients (age≤14 years) with an Head AIS ≥3, (64.0% males, mean age = 6.2 S.D. 4.58) presented over 10 years. Head AIS was strongly associated with mortality; with 0.8%, 1.1% and 42.0% of patients with Head AIS of 3, 4 and 5, respectively, dying - odds ratio for Head AIS 5 over Head AIS 3 = 89 (logistic regression, p-value<0.001). 80.0% of deaths (23 patients) in this cohort occurred within 24-h of presentation. Head AIS was associated with an increase likelihood of discharge to rehabilitation with 1.2%, 7.7% and 47.0% of survivors discharging to rehabilitation for Head AIS of 3, 4 and 5. CONCLUSION: Head AIS can reliably predict discharge disposition to home, rehab or death. Calculation of Head AIS prior to discharge could lead to accurate prediction of discharge destination.

Management of midline dural sinus malformations and review of the literature.

PURPOSE: Dural sinus malformations (DSMs) are rare pediatric vascular lesions that have variable presentations and outcomes. We present three cases of midline DSMs and discuss the treatment strategy employed for each lesion. A review of the literature was completed to summarize current literature and treatment practices. METHODS: A retrospective review of the electronic medical record and all available imaging studies was performed for each of our patients. RESULTS: Patient 1 had a prenatally diagnosed DSM which decreased in size despite no intervention. She was born without complication and continues to do well at 15 months of age. Patient 2 presented 2 weeks after birth with cardiac failure, intracranial hemorrhage, and seizures and imaging showed a large midline DSM with multiple high-flow shunts. She required multiple endovascular embolizations with complete occlusion of the lesion. At her 3-year follow-up, she was neurologically normal. The third patient was diagnosed prenatally with an enlarging DSM. Multiple endovascular embolizations, surgical decompression, cranial expansion, and CSF diversion were required for treatment. At her 2.5-year follow-up, she was meeting developmental milestones, with some motor delay. CONCLUSION: Early diagnosis and treatment, if necessary, of DSMs are critical to prevent cardiac failure or parenchymal injury from chronic venous hypertension. Management should be decided on individual case basis depending on the angioarchitecture and progression of the lesion and can involve observation, endovascular embolization, surgical interventions, or a combination of treatments. A personalized approach to treating these variable lesions can be associated with good outcomes.

Hearing loss in hydrocephalus: a review, with focus on mechanisms.

While neither hydrocephalus nor cerebrospinal fluid (CSF) shunt placement is traditionally considered in the differential diagnosis of hearing loss, there is substantial evidence that CSF circulation and pressure abnormalities can produce auditory dysfunction. Several indirect mechanisms may explain association between hydrocephalus and hearing loss, including mass effect, compromise of the auditory pathway, complications of prematurity, and genetically mediated hydrocephalus and hearing loss. Nevertheless, researchers have proposed a direct mechanism, which we term the hydrodynamic theory. In this hypothesis, the intimate relationship between CSF and inner ear fluids permits relative endolymphatic or perilymphatic hydrops in the setting of CSF pressure disturbances. CSF is continuous with perilymph, and CSF pressure changes are known to produce parallel perilymphatic pressure changes. In support of the hydrodynamic theory, some studies have found an independent association between hydrocephalus and hearing loss. Moreover, surgical shunting of CSF has been linked to both resolution and development of auditory dysfunction. The disease burden of hydrocephalus-associated hearing loss may be large, and because hydrocephalus and over-shunting are reversible, this relationship merits broader recognition. Hydrocephalic patients should be monitored for hearing loss, and hearing loss in a patient with shunted hydrocephalus should prompt further evaluation and possibly adjustment of shunt settings.

Expression of adiponectin, chemerin and visfatin in plasma and different tissues during a laying season in turkeys.

BACKGROUND: In mammals, adipose tissue is able to secrete various hormones called adipokines including adiponectin (ADP), chemerin (Chem) and visfatin (Visf) which are involved in controlling energy metabolism as well as reproductive functions. Visf receptor is still unknown whereas ADP and Chem mainly act through AdipoR1, AdipoR2 and CMKLR1 and GPR1 receptors, respectively. No studies have yet demonstrated the presence of these three adipokines in peripheral tissues, ovarian cells or turkey plasma. Here, we investigated the expression (mRNA and protein) of ADP, Chem, Visf and their receptors in peripheral tissues and ovarian cells (granulosa and theca cells) from hierarchical follicles. Furthermore, we determined the plasma profile of ADP, Visf and Chem at different physiological stages: start, peak and end of the laying period in Meleagris gallopavo turkeys. This data was correlated with the metabolic data (plasma glucose, triglycerides, cholesterol and phospholipids). METHODS: Tissue and ovarian cells mRNA and protein expression levels were determined by RT-qPCR and immunoblot, respectively. Plasma adipokines were measured by chicken ELISA and immunoblotting. RESULTS: In turkeys, Chem is mainly expressed in the liver while ADP and Visf are mainly expressed in the abdominal adipose tissue and pectoral muscles,respectively. As in mammals, AdipoR1 and AdipoR2 expression levels (mRNA and protein) are highly present in muscle and liver, respectively, whereas the mRNA expression of CMKLR1 and GPR1 is ubiquitous. In ovarian cells, ADP, Visf, Chem and their receptors are more highly expressed in theca cells than in granulosa cells excepted for AdipoR1. Furthermore, we found that plasma levels of ADP, Chem and Visf were reduced at the end of the laying period compared to the start of this period. At the plasma levels, the levels of these adipokines are strongly negatively correlated with glucose and only plasma Chem is negatively correlated with cholesterol, triglycerides and phospholipids. CONCLUSIONS: In turkeys, ADP, Visf and Chem and their receptors are expressed in peripheral tissues and ovarian cells. Plasma concentration of ADP, Visf and Chem decrease at the end of laying period and only plasma Chem is negatively correlated with levels of cholesterol, triglycerides and phospholipids levels during the entire laying period.

Acute injection and chronic perfusion of kisspeptin elicit gonadotropins release but fail to trigger ovulation in the mare.

Kisspeptin has emerged as the most potent gonadotropin-releasing hormone (GnRH) secretagogue and appears to represent the penultimate step in the central control of reproduction. In the sheep, we showed that kisspeptin could be used to manipulate gonadotropin secretion and control ovulation. Prompted by these results, we decided to investigate whether kisspeptin could be used as an ovulation-inducing agent in another photoperiodic domestic mammal, the horse. Equine kisspeptin-10 (eKp10) was administered intravenously as bolus injections or short- to long-term perfusions to Welsh pony mares, either during the anestrus season or at various stages of the cycle during the breeding season. In all the experimental conditions, eKp10 reliably increased peripheral concentrations of both luteinizing hormone and follicle-stimulating hormone. The nature of the response to eKp10 was consistent across experimental conditions and physiological states: the increase in gonadotropins was always rapid and essentially transient even when eKp10 was perfused for prolonged periods. Furthermore, eKp10 consistently failed to induce ovulation in the mare. To gain insights into the underlying mechanisms, we used acute injections or perfusions of GnRH. We also cloned the equine orthologues of the kisspeptin precursor and Kiss1r; this was justified by the facts that the current equine genome assembly predicted an amino acid difference between eKp10 and Kp10 in other species while an equine orthologue for Kiss1r was missing altogether. In light of these findings, potential reasons for the divergence in the response to kisspeptin between ewe and mare are discussed. Our data highlight that kisspeptin is not a universal ovulation-inducing agent.

The influence of nutrition on the insulin-like growth factor system and the concentrations of growth hormone, glucose, insulin, gonadotropins and progesterone in ovarian follicular fluid and plasma from adult female horses (Equus caballus).

BACKGROUND: Feed intake affects the GH-IGF system and may be a key factor in determining the ovarian follicular growth rate. In fat mares, the plasma IGF-1 concentration is high with low GH and a quick follicular growth rate, in contrast to values observed in thin mares. Nothing is known regarding the long-term effects of differential feed intake on the IGF system. The objective of this experiment was to quantify IGFs, IGFBPs, GH, glucose, insulin, gonadotropin and progesterone (P4) in blood and in preovulatory follicular fluid (FF) in relation to feeding levels in mares. METHODS: Three years prior to the experiment, Welsh Pony mares were assigned to a restricted diet group (R, n = 10) or a well-fed group (WF, n = 9). All mares were in good health and exhibited differences in body weight and subcutaneous fat thickness. Follicular development was scanned daily and plasma was also collected daily. Preovulatory FF was collected by ultrasound-guided follicular aspiration. Hormone levels were assayed in FF and plasma with a validated RIA. RESULTS: According to scans, the total number of follicles in group R was 53% lower than group WF. Insulin and IGF-1 concentrations were higher in WF than in R mares. GH and IGF-2 concentrations were lower in plasma from WF mares than from R mares, but the difference was not significant in FF. The IGFBP-2/IGFBP-3 ratio in FF was not affected by feeding but was dramatically increased in R mare plasma. No difference in gonadotropin concentration was found with the exception of FSH, which was higher in the plasma of R mares. On the day of puncture, P4 concentrations were not affected by feeding but were higher in preovulatory FF than in plasma. CONCLUSIONS: The bioavailability of IGF-1 or IGF-2, represented by the IGFBP2/IGFBP3 ratio, is modified by feed intake in plasma but not in FF. These differences partially explain the variability in follicular growth observed between well-fed mares and mares on restricted diets.

Pilomyxoid astrocytoma treated successfully with vemurafenib.

The BRAF V600E missense mutation is known to be present in a subset of central nervous system tumors. We report a patient with a BRAF V600E mutated pilomyxoid astrocytoma who failed multiple conventional chemotherapy regimens. Treatment with vemurafenib, a molecularly targeted therapy against the mutant BRAF V600E kinase, combined with vinblastine resulted in tumor regression. Furthermore, this patient experienced almost immediate progression of disease after holding vemurafenib for only 2-3 weeks, suggesting that the tumor response is vemurafenib dependent. This population of patients may benefit from targeted therapy and testing of individual tumors for BRAF mutations is justified.

The role of occipital condyle and atlas anomalies on occipital cervical fusion outcomes in Chiari malformation type I with syringomyelia: a study from the Park-Reeves Syringomyelia Research Consortium.

OBJECTIVE: Congenital anomalies of the atlanto-occipital articulation may be present in patients with Chiari malformation type I (CM-I). However, it is unclear how these anomalies affect the biomechanical stability of the craniovertebral junction (CVJ) and whether they are associated with an increased incidence of occipitocervical fusion (OCF) following posterior fossa decompression (PFD). The objective of this study was to determine the prevalence of condylar hypoplasia and atlas anomalies in children with CM-I and syringomyelia. The authors also investigated the predictive contribution of these anomalies to the occurrence of OCF following PFD (PFD+OCF). METHODS: The authors analyzed the prevalence of condylar hypoplasia and atlas arch anomalies for patients in the Park-Reeves Syringomyelia Research Consortium database who underwent PFD+OCF. Condylar hypoplasia was defined by an atlanto-occipital joint axis angle (AOJAA) ≥ 130°. Atlas assimilation and arch anomalies were identified on presurgical radiographic imaging. This PFD+OCF cohort was compared with a control cohort of patients who underwent PFD alone. The control group was matched to the PFD+OCF cohort according to age, sex, and duration of symptoms at a 2:1 ratio. RESULTS: Clinical features and radiographic atlanto-occipital joint parameters were compared between 19 patients in the PFD+OCF cohort and 38 patients in the PFD-only cohort. Demographic data were not significantly different between cohorts (p > 0.05). The mean AOJAA was significantly higher in the PFD+OCF group than in the PFD group (144° ± 12° vs 127° ± 6°, p < 0.0001). In the PFD+OCF group, atlas assimilation and atlas arch anomalies were identified in 10 (53%) and 5 (26%) patients, respectively. These anomalies were absent (n = 0) in the PFD group (p < 0.001). Multivariate regression analysis identified the following 3 CVJ radiographic variables that were predictive of OCF occurrence after PFD: AOJAA ≥ 130° (p = 0.01), clivoaxial angle < 125° (p = 0.02), and occipital condyle-C2 sagittal vertical alignment (C-C2SVA) ≥ 5 mm (p = 0.01). A predictive model based on these 3 factors accurately predicted OCF following PFD (C-statistic 0.95). CONCLUSIONS: The authors' results indicate that the occipital condyle-atlas joint complex might affect the biomechanical integrity of the CVJ in children with CM-I and syringomyelia. They describe the role of the AOJAA metric as an independent predictive factor for occurrence of OCF following PFD. Preoperative identification of these skeletal abnormalities may be used to guide surgical planning and treatment of patients with complex CM-I and coexistent osseous pathology.

Dual contrast perfusion MRI in a single imaging session for assessment of pediatric brain tumors.

Ferumoxytol, an iron nanoparticle used as an intravascular contrast agent for perfusion magnetic resonance imaging (MRI), has never been explored in the pediatric population. The purpose of this prospective study is to characterize the vascular and permeability properties of pediatric brain tumors using two contrast agents during a single imaging session: ferumoxytol for dynamic susceptibility weighted contrast (DSC) MRI and gadoteridol for dynamic contrast-enhanced (DCE) MRI. In a single imaging session, patients received intravenous ferumoxytol for DSC MRI followed by gadoteridol for DCE MRI. Relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF), transfer coefficient (K(trans)), and extravascular extracellular space volume fraction (v(e)) of the brain lesions were calculated. Patients underwent serial imaging sessions over the course of 2 years. Of the 7 patients enrolled thus far, none has experienced an adverse event. Two patients with medulloblastoma were enrolled preoperatively. In the first, rCBV(max), rCBF, K(trans) max, and v(e) max values were 3.74, 3.12, 0.47 min (-1), and 0.08, respectively, while in the second patient, rCBV(max), rCBF, K(trans) max, and v(e) max values were 4.72, 3.47, 0.60 min(-1), and 0.05, respectively. Four patients were enrolled after new gadolinium enhancement was noted in the tumor resection cavity. In 80 % of these lesions, rCBV was <1 suggestive of pseudoprogression secondary to radiochemotherapy. These preliminary results demonstrate that use of ferumoxytol and gadoteridol contrast agents during a single imaging session is feasible, safe, and appears useful for assessing tumor perfusion and permeability characteristics in children.

Photoperiod modulates access of 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153) to the brain and its effect on gonadotropin and thyroid hormones in adult ewes.

The effects of photoperiod on the cerebrospinal fluid (CSF) concentration of six ortho-substituted polychlorinated biphenyls (PCBs: PCB28, PCB52, PCB101, PCB138, PCB153, and PCB180), the effects of an orally administered low dose of PCB153 (0.3mg/kg, three times a week for three weeks) on PCBs and thyroid hormones (THs) concentrations in the CSF and plasma, and the release of luteinizing hormone (LH) were determined in ovariectomized, estradiol-implanted ewes (2.5 years old) maintained indoors under artificial long day (LD, 16L: 8D) and short day (SD, 8L: 16D) conditions. Concentrations of two PCBs (PCB28 and PCB153) in the plasma and four PCBs in the CSF (PCB101, PCB138, PCB153, and PCB180) were significantly higher during LD than SD. Following PCB153 treatment, its concentration in the plasma was higher in SD (1.2 ± 0.3 ng/ml) than LD (0.2 ± 0.05 ng/ml), but similar in the CSF (10.2 ± 3.7 pg/ml vs. 13 ± 0.7 pg/ml) under both photoperiods. During SD, the concentration of PCB153 in the CSF was higher in treated animals than controls, while no differences were noted under LD. These findings indicate that in ewes, exposure of the brain to more highly chlorinated, ortho-substituted PCBs may be modulated by photoperiod. PCB153 treatment had no effect on plasma THs, but reduced total triiodothyronine concentration during LD and free thyroxine during SD in the CSF. Under both photoperiods, PCB153 reduced basal plasma LH and reinforced the inhibition of pulsatile LH release during LD. As PCB153 reduced LH and THs (which are involved in the seasonal control of reproduction in ewes), it may have a braking effect on seasonal transitions between active and inactive phases of reproduction.

Cerebral spinal fluid overdrainage from shunt tap using large bore coring needle: A case report.

Background: Tapping a ventriculoperitoneal shunt percutaneously using a coring needle, such as a butterfly needle, is a common neurosurgical practice despite manufacturers' recommendation to use a Huber type non-coring needle. Case Description: A 26-year-old woman, with congenital hydrocephalus and history of multiple shunt revision and shunt taps, presented with symptoms consistent with intracranial hypotension. During her shunt revision, cerebrospinal fluid (CSF) was found to be leaking from her shunt reservoir defects which were believed to be caused by prior shunt taps. An in vitro study duplicated this finding in which several areas of leak were observed from the valve tapped using the coring needle, while none was observed from the valve tapped using the non-coring needle. Conclusion: Taping a shunt using a coring needle can damage the shunt reservoir and cause CSF overdrainage.

Estimating Risk of Pituitary Apoplexy after Resection of Giant Pituitary Adenomas.

Background Pituitary apoplexy after resection of giant pituitary adenomas is a rare but often cited morbidity associated with devastating outcomes. It presents as hemorrhage and/or infarction of residual tumor in the postoperative period. Because of its rarity, its incidence and consequences remain ill defined. Objective The aim of this study is to estimate the rate of postoperative pituitary apoplexy after resection of giant pituitary adenomas and assess the morbidity and mortality associated with apoplexy. Methods A systematic review of literature was performed to examine extent of resection in giant pituitary adenomas based on surgical approach, rate of postoperative apoplexy, morbidities, and mortality. Advantages and disadvantages of each approach were compared. Results Seventeen studies were included in quantitative analysis describing 1,031 cases of resection of giant pituitary adenomas. The overall rate of subtotal resection (<90%) for all surgical approaches combined was 35.6% (95% confidence interval: 28.0-43.1). Postoperative pituitary apoplexy developed in 5.65% ( n = 19) of subtotal resections, often within 24 hours and with a mortality of 42.1% ( n = 8). Resulting morbidities included visual deficits, altered consciousness, cranial nerve palsies, and convulsions. Conclusion Postoperative pituitary apoplexy is uncommon but is associated with high rates of morbidity and mortality in subtotal resection cases. These findings highlight the importance in achieving a maximal resection in a time sensitive fashion to mitigate the severe consequences of postoperative apoplexy.

Learning Curve Associated with ClearPoint Neuronavigation System: A Case Series.

BACKGROUND: The ClearPoint neuronavigation system affords real-time magnetic resonance imaging (MRI) guidance during stereotactic procedures. While such information confers potential clinical benefits, additional operative time may be needed. METHODS: We conducted a retrospective analysis of procedural time associated with ClearPoint Stereotaxis, with hypothesis that this procedural time is comparable with that associated with frame-based biopsy. RESULTS: Of the 52 patients evaluated, the total procedural time for ClearPoint stereotactic biopsy averaged 150.0 (±40.4) minutes, of which 111.5 (±16.5) minutes were dedicated to real-time MRI acquisition and trajectory adjustment. This procedural time is within the range of those reported for frame-based needle biopsies. Approximately 5 minutes of the procedural time is related to the mounting of the MRI-compatible stereotactic frame. Based on the procedural time, we estimate that four cases are required in the learning curve to achieve this efficiency. Efficient algorithms for distortion corrections and isocenter localization are keys to ClearPoint stereotaxis. Routine quality assurance/control after each MRI software update and institutional information technology maintenance also contribute to efficiency. Real-time MRI is essential for definitive diagnosis in select cases. CONCLUSIONS: ClearPoint stereotactic needle biopsy can be achieved in time frames comparable to frame-based stereotaxis. However, procedural efficiency requires 4 "learning curve" cases as well as vigilance in terms of MR distortion correction and information technology maintenance.

Complications and outcomes of posterior fossa decompression with duraplasty versus without duraplasty for pediatric patients with Chiari malformation type I and syringomyelia: a study from the Park-Reeves Syringomyelia Research Consortium.

OBJECTIVE: The aim of this study was to determine differences in complications and outcomes between posterior fossa decompression with duraplasty (PFDD) and without duraplasty (PFD) for the treatment of pediatric Chiari malformation type I (CM1) and syringomyelia (SM). METHODS: The authors used retrospective and prospective components of the Park-Reeves Syringomyelia Research Consortium database to identify pediatric patients with CM1-SM who received PFD or PFDD and had at least 1 year of follow-up data. Preoperative, treatment, and postoperative characteristics were recorded and compared between groups. RESULTS: A total of 692 patients met the inclusion criteria for this database study. PFD was performed in 117 (16.9%) and PFDD in 575 (83.1%) patients. The mean age at surgery was 9.86 years, and the mean follow-up time was 2.73 years. There were no significant differences in presenting signs or symptoms between groups, although the preoperative syrinx size was smaller in the PFD group. The PFD group had a shorter mean operating room time (p < 0.0001), fewer patients with > 50 mL of blood loss (p = 0.04), and shorter hospital stays (p = 0.0001). There were 4 intraoperative complications, all within the PFDD group (0.7%, p > 0.99). Patients undergoing PFDD had a 6-month complication rate of 24.3%, compared with 13.7% in the PFD group (p = 0.01). There were no differences between groups for postoperative complications beyond 6 months (p = 0.33). PFD patients were more likely to require revision surgery (17.9% vs 8.3%, p = 0.002). PFDD was associated with greater improvements in headaches (89.6% vs 80.8%, p = 0.04) and back pain (86.5% vs 59.1%, p = 0.01). There were no differences between groups for improvement in neurological examination findings. PFDD was associated with greater reduction in anteroposterior syrinx size (43.7% vs 26.9%, p = 0.0001) and syrinx length (18.9% vs 5.6%, p = 0.04) compared with PFD. CONCLUSIONS: PFD was associated with reduced operative time and blood loss, shorter hospital stays, and fewer postoperative complications within 6 months. However, PFDD was associated with better symptom improvement and reduction in syrinx size and lower rates of revision decompression. The two surgeries have low intraoperative complication rates and comparable complication rates beyond 6 months.

Socioeconomic and demographic factors in the diagnosis and treatment of Chiari malformation type I and syringomyelia.

OBJECTIVE: The goal of this study was to assess the social determinants that influence access and outcomes for pediatric neurosurgical care for patients with Chiari malformation type I (CM-I) and syringomyelia (SM). METHODS: The authors used retro- and prospective components of the Park-Reeves Syringomyelia Research Consortium database to identify pediatric patients with CM-I and SM who received surgical treatment and had at least 1 year of follow-up data. Race, ethnicity, and insurance status were used as comparators for preoperative, treatment, and postoperative characteristics and outcomes. RESULTS: A total of 637 patients met inclusion criteria, and race or ethnicity data were available for 603 (94.7%) patients. A total of 463 (76.8%) were non-Hispanic White (NHW) and 140 (23.2%) were non-White. The non-White patients were older at diagnosis (p = 0.002) and were more likely to have an individualized education plan (p < 0.01). More non-White than NHW patients presented with cerebellar and cranial nerve deficits (i.e., gait ataxia [p = 0.028], nystagmus [p = 0.002], dysconjugate gaze [p = 0.03], hearing loss [p = 0.003], gait instability [p = 0.003], tremor [p = 0.021], or dysmetria [p < 0.001]). Non-White patients had higher rates of skull malformation (p = 0.004), platybasia (p = 0.002), and basilar invagination (p = 0.036). Non-White patients were more likely to be treated at low-volume centers than at high-volume centers (38.7% vs 15.2%; p < 0.01). Non-White patients were older at the time of surgery (p = 0.001) and had longer operative times (p < 0.001), higher estimated blood loss (p < 0.001), and a longer hospital stay (p = 0.04). There were no major group differences in terms of treatments performed or complications. The majority of subjects used private insurance (440, 71.5%), whereas 175 (28.5%) were using Medicaid or self-pay. Private insurance was used in 42.2% of non-White patients compared to 79.8% of NHW patients (p < 0.01). There were no major differences in presentation, treatment, or outcome between insurance groups. In multivariate modeling, non-White patients were more likely to present at an older age after controlling for sex and insurance status (p < 0.01). Non-White and male patients had a longer duration of symptoms before reaching diagnosis (p = 0.033 and 0.004, respectively). CONCLUSIONS: Socioeconomic and demographic factors appear to influence the presentation and management of patients with CM-I and SM. Race is associated with age and timing of diagnosis as well as operating room time, estimated blood loss, and length of hospital stay. This exploration of socioeconomic and demographic barriers to care will be useful in understanding how to improve access to pediatric neurosurgical care for patients with CM-I and SM.

Effects of nutritional cues on the duration of the winter anovulatory phase and on associated hormone levels in adult female Welsh pony horses (Equus caballus).

BACKGROUND: Mares have an annual reproductive rhythm, with a phase of inactivity in midwinter. The aim of this study was to determine the impact of food restriction on physiological and metabolic hallmarks of this rhythm. METHODS: Over three successive years, 3 groups of 10 mares were kept under natural photoperiod. A 'well-fed' group was fed to maintain the mares in good body condition; a 'restricted' group received a diet calculated to keep the mares thin and a 'variable' group was fed during some periods like the 'restricted' group and during some other periods like the 'well-fed' group, with the aim of mimicking the natural seasonal variation of pasture availability, but a few months in advance of this natural rhythm. RESULTS: Winter ovarian inactivity always occurred and was long in the restricted group. In contrast, in the 'well-fed' group, 40% of mares showed this inactivity, which was shorter than in the other groups. Re-feeding the 'variable' group in autumn and winter did not advance the first ovulation in spring, compared with the 'restricted' group. Measurements of glucose and insulin concentrations in mares from the 'restricted' group during two 24 h periods of blood sampling, revealed no post-prandial peaks. For GH (Growth hormone), IGF-1 and leptin levels, large differences were found between the 'well-fed' group and the other groups. The glucose, insulin, GH and leptin levels but not melatonin level are highly correlated with the duration of ovulatory activity. CONCLUSIONS: The annual rhythm driven by melatonin secretion is only responsible for the timing of the breeding season. The occurrence and length of winter ovarian inactivity is defined by metabolic hormones.

Cognitive performance in relapsing remitting multiple sclerosis: a longitudinal study in daily practice using a brief computerized cognitive battery.

BACKGROUND: There is need for a cognitive test battery that can be easily used in clinical practice to detect or monitor cognitive performance in patients with multiple sclerosis (MS). In order to conduct, in this patient group, a preliminary investigation of the validity and utility of a brief computerized battery, the Cognitive Drug Research (CDR) battery, we longitudinally assessed cognition in patients with relapsing remitting (RR) MS. METHODS: Forty-three mildly disabled, clinically active RRMS patients were repeatedly assessed with the Digit Symbol Substitution Test (DSST), Paced Auditory Serial Addition Test (PASAT) and five composite scores derived from the CDR computerized cognitive test system (CDR System): Power of Attention, Continuity of Attention, Quality of Working Memory, Quality of Episodic Memory and Speed of Memory. The Multiple Sclerosis Functional Composite (MSFC) and Expanded Disability Status Scale (EDSS) measured disability. RESULTS: The composite scores from the CDR battery generally showed excellent test-retest reliability over the repeated assessments, though was low on occasions for the Quality of Working Memory and Quality of Episodic Memory measures. The CDR measures tended to be highly correlated with other measures of cognition (DSST and PASAT) and were also strongly related to disability (EDSS and MSFC). Baseline scores indicated large impairments to visual information processing speed and attention (DSST, Cohen's d 1.1; Power of Attention d 1.4 [reaction time on tasks of focussed and sustained attention]), and a moderate impairment both to sustained attention (Continuity of Attention d 0.6) and complex information processing speed (Speed of memory d 0.7 [reaction time on tasks of working and episodic Memory]), when compared to normative data derived from healthy volunteers enrolled in a series of separate, prior clinical trials. Working memory (Quality of Working Memory) and episodic memory (Quality of Episodic Memory) were unimpaired. CONCLUSIONS: Preliminary validation of the CDR System indicated that for most, but not all measures psychometric properties were adequate and the measures were related to disability (EDSS and MSFC) and other measures of cognition.