Cortical volume abnormalities in schizophrenia: Correlations with symptoms and cognitive impairment.

BACKGROUND: Schizophrenic symptoms are known to segregate into reality distortion, negative and disorganization syndromes, but the correlates of these syndromes with regional brain structural change are not well established. Cognitive impairment is a further clinical feature of schizophrenia, whose brain structural correlates are the subject of conflicting findings. METHODS: 165 patients with schizophrenia were rated for symptoms using the PANSS, and cognitive impairment was indexed by estimated premorbid-current IQ discrepancy. Cortical volume was measured using surface-based morphometry in the patients and in 50 healthy controls. Correlations between clinical and cognitive measures and cortical volume were examined using whole-brain FreeSurfer tools. RESULTS: No clusters of volume reduction were seen associated with reality distortion or disorganization. Negative symptom scores showed a significant inverse correlation with volume in a small cluster in the left medial orbitofrontal gyrus. Larger estimated premorbid-current IQ discrepancies were associated with clusters of reduced cortical volume in the left precentral gyrus and the left temporal lobe. The cluster of association with negative symptoms disappeared when estimated premorbid-current IQ discrepancy was controlled for. CONCLUSIONS: This study does not provide support for an association between brain structural abnormality and reality distortion or disorganization syndromes in schizophrenia. The cluster of volume reduction found in the left medial orbitofrontal cortex correlated with negative symptoms may have reflected the association between this class of symptoms and cognitive impairment. The study adds to existing findings of an association between cognitive impairment and brain structural changes in the disorder.

MRI Gadolinium-Based Contrast Media: Meeting Radiological, Clinical, and Environmental Needs.

Gadolinium-based contrast agents (GBCAs) are routinely used in magnetic resonance imaging (MRI). They are essential for choosing the most appropriate medical or surgical strategy for patients with serious pathologies, particularly in oncologic, inflammatory, and cardiovascular diseases. However, GBCAs have been associated with an increased risk of nephrogenic systemic fibrosis in patients with renal failure, as well as the possibility of deposition in the brain, bones, and other organs, even in patients with normal renal function. Research is underway to reduce the quantity of gadolinium injected, without compromising image quality and diagnosis. The next generation of GBCAs will enable a reduction in the gadolinium dose administered. Gadopiclenol is the first of this new generation of GBCAs, with high relaxivity, thus having the potential to reduce the gadolinium dose while maintaining good in vivo stability due to its macrocyclic structure. High-stability and high-relaxivity GBCAs will be one of the solutions for reducing the dose of gadolinium to be administered in clinical practice, while the development of new technologies, including optimization of MRI acquisitions, new contrast mechanisms, and artificial intelligence may help reduce the need for GBCAs. Future solutions may involve a combination of next-generation GBCAs and image-processing techniques to optimize diagnosis and treatment planning while minimizing exposure to gadolinium. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 3.

Improved estimation of the risk of manic relapse by combining clinical and brain scan data.

INTRODUCTION: Estimating the risk of manic relapse could help the psychiatrist individually adjust the treatment to the risk. Some authors have attempted to estimate this risk from baseline clinical data. Still, no studies have assessed whether the estimation could improve by adding structural magnetic resonance imaging (MRI) data. We aimed to evaluate it. MATERIAL AND METHODS: We followed a cohort of 78 patients with a manic episode without mixed symptoms (bipolar type I or schizoaffective disorder) at 2-4-6-9-12-15-18 months and up to 10 years. Within a cross-validation scheme, we created and evaluated a Cox lasso model to estimate the risk of manic relapse using both clinical and MRI data. RESULTS: The model successfully estimated the risk of manic relapse (Cox regression of the time to relapse as a function of the estimated risk: hazard ratio (HR)=2.35, p=0.027; area under the curve (AUC)=0.65, expected calibration error (ECE)<0.2). The most relevant variables included in the model were the diagnosis of schizoaffective disorder, poor impulse control, unusual thought content, and cerebellum volume decrease. The estimations were poorer when we used clinical or MRI data separately. CONCLUSION: Combining clinical and MRI data may improve the risk of manic relapse estimation after a manic episode. We provide a website that estimates the risk according to the model to facilitate replication by independent groups before translation to clinical settings.

A state-of-the-art guide about the effects of sterilization processes on 3D-printed materials for surgical planning and medical applications: A comparative study.

Surgeons use different medical devices in the surgery, such as patient-specific anatomical models, cutting and positioning guides, or implants. These devices must be sterilized before being used in the operation room. There are many sterilization processes available, with autoclave, hydrogen peroxide, and ethylene oxide being the most common in hospital settings. Each method has both advantages and disadvantages in terms of mechanics, chemical interaction, and post-treatment accuracy. The aim of the present study is to evaluate the dimensional and mechanical effect of the most commonly used sterilization techniques available in clinical settings, i.e., Autoclave 121, Autoclave 134, and hydrogen peroxide (HPO), on 11 of the most used 3D-printed materials fabricated using additive manufacturing technologies. The results showed that the temperature (depending on the sterilization method) and the exposure time to that temperature influence not only the mechanical behavior but also the original dimensioning planned on the 3D model. Therefore, HPO is a better overall option for most of the materials evaluated. Finally, based on the results of the study, a recommendation guide on sterilization methods per material, technology, and clinical application is presented.

Exploring the Potential of Three-Dimensional Imaging, Printing, and Modeling in Pediatric Surgical Oncology: A New Era of Precision Surgery.

Pediatric surgical oncology is a technically challenging field that relies on CT and MRI as the primary imaging tools for surgical planning. However, recent advances in 3D reconstructions, including Cinematic Rendering, Volume Rendering, 3D modeling, Virtual Reality, Augmented Reality, and 3D printing, are increasingly being used to plan complex cases bringing new insights into pediatric tumors to guide therapeutic decisions and prognosis in different pediatric surgical oncology areas and locations including thoracic, brain, urology, and abdominal surgery. Despite this, challenges to their adoption remain, especially in soft tissue-based specialties such as pediatric surgical oncology. This work explores the main innovative imaging reconstruction techniques, 3D modeling technologies (CAD, VR, AR), and 3D printing applications through the analysis of three real cases of the most common and surgically challenging pediatric tumors: abdominal neuroblastoma, thoracic inlet neuroblastoma, and a bilateral Wilms tumor candidate for nephron-sparing surgery. The results demonstrate that these new imaging and modeling techniques offer a promising alternative for planning complex pediatric oncological cases. A comprehensive analysis of the advantages and limitations of each technique has been carried out to assist in choosing the optimal approach.

Perspectives on medical 3D printing at the point-of-care from the new European 3D Printing Special Interest Group.

This editorial presents the vision for the newly formed (2022) European 3D Special Interest Group (EU3DSIG) in the landscape of medical 3D printing. There are four areas of work identified by the EU3DSIG in the current landscape, namely: 1) creating and fostering communication channels among researches, clinicians and industry, 2) generating awareness of hospitals point-of-care 3D technologies; 3) knowledge sharing and education; 4) regulation, registry and reimbursement models.

3D printing as surgical planning and training in pediatric endoscopic skull base surgery - Systematic review and practical example.

BACKGROUND: Pediatric endoscopic skull base surgery is challenging due to the intricate anatomy of the skull base and the presence of tumors with varied pathologies. The use of three-dimensional (3D) printing technologies in skull base surgeries has been found to be highly beneficial. A systematic review of the literature was performed to investigate the published studies that reported the effectiveness of 3D printing in pediatric endoscopic skull base surgery. METHODS: Pub Med, Embase, Science Direct, The Cochrane Library, and Scopus were searched from January 01, 2000, until June 30, 2022. Original articles of any design reporting on the effectiveness of 3D printing in pediatric endoscopic skull base surgery were included. Information related to study population, conditions, models used, and key findings of study were extracted. Quality of included studies was evaluated using the Joanna Briggs Institute's (JBI) Critical Appraisal Checklist for Studies. To exemplify the use of 3D technology in this scenario, we report a complex clival chordoma case. RESULTS: Six research articles were retrieved and included for qualitative analysis. Four of the six studies were conducted in the United States, followed by two in China. According to these studies, 3D reconstruction and printed models were more beneficial than CT/MRI images when discussing surgery with patients. In clinical training, these models were more helpful than 2D images in understanding the pathology when used in conjunction with image-guiding systems. It has been found that patient-specific 3D modeling, simulations, and rehearsal are the most efficient preoperative planning techniques, particularly in the pediatric population, for the treatment of complicated skull base surgeries. All the studies had a moderate risk of bias. CONCLUSION: 3D printing technologies assist in printing complex skull base tumors and the structures around them in three dimensions at the point of care and at the time needed, enabling the choice of the appropriate surgical strategy, thus minimizing surgery-related complications.

Patient-Specific 3D Printed Soft Models for Liver Surgical Planning and Hands-On Training.

Background: Pre-surgical simulation-based training with three-dimensional (3D) models has been intensively developed in complex surgeries in recent years. This is also the case in liver surgery, although with fewer reported examples. The simulation-based training with 3D models represents an alternative to current surgical simulation methods based on animal or ex vivo models or virtual reality (VR), showing reported advantages, which makes the development of realistic 3D-printed models an option. This work presents an innovative, low-cost approach for producing patient-specific 3D anatomical models for hands-on simulation and training. Methods: The article reports three paediatric cases presenting complex liver tumours that were transferred to a major paediatric referral centre for treatment: hepatoblastoma, hepatic hamartoma and biliary tract rhabdomyosarcoma. The complete process of the additively manufactured liver tumour simulators is described, and the different steps for the correct development of each case are explained: (1) medical image acquisition; (2) segmentation; (3) 3D printing; (4) quality control/validation; and (5) cost. A digital workflow for liver cancer surgical planning is proposed. Results: Three hepatic surgeries were planned, with 3D simulators built using 3D printing and silicone moulding techniques. The 3D physical models showed highly accurate replications of the actual condition. Additionally, they proved to be more cost-effective in comparison with other models. Conclusions: It is demonstrated that it is possible to manufacture accurate and cost-effective 3D-printed soft surgical planning simulators for treating liver cancer. The 3D models allowed for proper pre-surgical planning and simulation training in the three cases reported, making it a valuable aid for surgeons.

Early and Delayed Infarct Growth in Patients Undergoing Mechanical Thrombectomy: A Prospective, Serial MRI Study.

BACKGROUND: We studied the evolution over time of diffusion weighted imaging (DWI) lesion volume and the factors involved on early and late infarct growth (EIG and LIG) in stroke patients undergoing endovascular treatment (EVT) according to the final revascularization grade. METHODS: This is a prospective cohort of patients with anterior large artery occlusion undergoing EVT arriving at 1 comprehensive stroke center. Magnetic resonance imaging was performed on arrival (pre-EVT), <2 hours after EVT (post-EVT), and on day 5. DWI lesions and perfusion maps were evaluated. Arterial revascularization was assessed according to the modified Thrombolysis in Cerebral Infarction (mTICI) grades. We recorded National Institutes of Health Stroke Scale at arrival and at day 7. EIG was defined as (DWI volume post-EVT-DWI volume pre-EVT), and LIG was defined as (DWI volume at 5d-DWI volume post-EVT). Factors involved in EIG and LIG were tested via multivariable lineal models. RESULTS: We included 98 patients (mean age 70, median National Institutes of Health Stroke Scale score 17, final mTICI≥2b 86%). Median EIG and LIG were 48 and 63.3 mL in patients with final mTICI<2b, and 3.6 and 3.9 cc in patients with final mTICI≥2b. Both EIG and LIG were associated with higher National Institutes of Health Stroke Scale at day 7 (ρ=0.667; P<0.01 and ρ=0.614; P<0.01, respectively). In patients with final mTICI≥2b, each 10% increase in the volume of DWI pre-EVT and each extra pass leaded to growths of 9% (95% CI, 7%-10%) and 14% (95% CI, 2%-28%) in the DWI volume post-EVT, respectively. Furthermore, each 10% increase in the volume of DWI post-EVT, each extra pass, and each 10 mL increase in TMax6s post-EVT were associated with growths of 8% (95% CI, 6%-9%), 9% (95% CI, 0%-19%), and 12% (95% CI, 5%-20%) in the volume of DWI post-EVT, respectively. CONCLUSIONS: Infarct grows during and after EVT, especially in nonrecanalizers but also to a lesser extent in recanalizers. In recanalizers, number of passes and DWI volume influence EIG, while number of passes, DWI, and hypoperfused volume after the procedure determine LIG.

Neural correlates of referential/persecutory delusions in schizophrenia: examination using fMRI and a virtual reality underground travel paradigm.

BACKGROUND: The brain functional correlates of delusions have been relatively little studied. However, a virtual reality paradigm simulating travel on the London Underground has been found to evoke referential ideation in both healthy subjects and patients with schizophrenia, making brain activations in response to such experiences potentially identifiable. METHOD: Ninety patients with schizophrenia/schizoaffective disorder and 28 healthy controls underwent functional magnetic resonance imaging while they viewed virtual reality versions of full and empty Barcelona Metro carriages. RESULTS: Compared to the empty condition, viewing the full carriage was associated with activations in the visual cortex, the cuneus and precuneus/posterior cingulate cortex, the inferior parietal cortex, the angular gyrus and parts of the middle and superior temporal cortex including the temporoparietal junction bilaterally. There were no significant differences in activation between groups. Nor were there activations associated with referentiality or presence of delusions generally in the patient group. However, patients with persecutory delusions showed a cluster of reduced activation compared to those without delusions in a region in the right temporal/occipital cortex. CONCLUSIONS: Performance of the metro task is associated with a widespread pattern of activations, which does not distinguish schizophrenic patients and controls, or show an association with referentiality or delusions in general. However, the finding of a cluster of reduced activation close to the right temporoparietal junction in patients with persecutory delusions specifically is of potential interest, as this region is believed to play a role in social cognition.

Intracranial atherosclerotic plaque enhancement and long-term risk of future strokes: A prospective, longitudinal study.

BACKGROUND AND PURPOSE: The prognostic significance of postcontrast enhancement of intracranial atheromatous plaque is uncertain. Prospective, long-term follow-up studies in Caucasians, using a multicenter design, are lacking. We aimed to evaluate whether this radiological sign predicts long-term new stroke in symptomatic and asymptomatic intracranial atherosclerotic disease (ICAD) patients. METHODS: This was a prospective, observational, longitudinal, multicenter study. We included a symptomatic and an asymptomatic cohort of ICAD patients that underwent 3T MRI including high-resolution sequences focused on the atheromatous plaque. We evaluated grade of stenosis, plaque characteristics, and gadolinium enhancement ratio (postcontrast plaque signal/postcontrast corpus callosum signal). The occurrence of new events was evaluated at 3, 6, 9, and 12 months and annually thereafter. The association between plaque characteristics and new stroke was studied using Cox multiple regression survival analysis and Kaplan-Meier curves. RESULTS: Forty-eight symptomatic and 13 asymptomatic patients were included. During 56.3 ± 16.9 months, 11 patients (18%) suffered a new event (seven ischemic, two hemorrhagic, and two transient ischemic attacks). A receiver operating characteristic curve identified an enhancement ratio of >1.77 to predict a new event. In a multivariable Cox regression, postcontrast enhancement ratio >1.77 (hazard ratio [HR]= 3.632; 95% confidence interval [CI], 1.082-12.101) and cerebral microbleeds (HR = 5.244; 95% CI, 1.476-18.629) were independent predictors of future strokes. Patients with a plaque enhancement ratio >1.77 had a lower survival free of events (p < .05). CONCLUSIONS: High intracranial postcontrast enhancement is a long-term predictor of new stroke in ICAD patients. Further studies are needed to elucidate whether postcontrast enhancement reflects inflammatory activity of intracranial atheromatous plaque.

Brain correlates of impaired goal management in bipolar mania.

BACKGROUND: Although executive impairment has been reported in mania, its brain functional correlates have been relatively little studied. This study examined goal management, believed to be more closely related to executive impairment in daily life than other executive tasks, using a novel functional magnetic resonance imaging (fMRI) paradigm in patients in this illness phase. METHODS: Twenty-one currently manic patients with bipolar disorder and 30 matched healthy controls were scanned while performing the Computerized Multiple Elements Test (CMET). This requires participants to sequentially play four simple games, with transition between games being made either voluntarily (executive condition) or automatically (control condition). RESULTS: CMET performance was impaired in the manic patients compared to the healthy controls. Manic patients failed to increase activation in the lateral frontal, cingulate and inferior parietal cortex when the executive demands of the task increased, while this increase was observed in the healthy controls. Activity in these regions was associated with task performance. CONCLUSIONS: Manic patients show evidence of impaired goal management, which is associated with a pattern of reduced medial and lateral frontal and parietal activity.

Advanced Strategies for the Fabrication of Multi-Material Anatomical Models of Complex Pediatric Oncologic Cases.

The printing and manufacturing of anatomical 3D models has gained popularity in complex surgical cases for surgical planning, simulation and training, the evaluation of anatomical relations, medical device testing and patient-professional communication. 3D models provide the haptic feedback that Virtual or Augmented Reality (VR/AR) cannot provide. However, there are many technologies and strategies for the production of 3D models. Therefore, the aim of the present study is to show and compare eight different strategies for the manufacture of surgical planning and training prototypes. The eight strategies for creating complex abdominal oncological anatomical models, based on eight common pediatric oncological cases, were developed using four common technologies (stereolithography (SLA), selectie laser sinterning (SLS), fused filament fabrication (FFF) and material jetting (MJ)) along with indirect and hybrid 3D printing methods. Nine materials were selected for their properties, with the final models assessed for application suitability, production time, viscoelastic mechanical properties (shore hardness and elastic modulus) and cost. The manufacturing and post-processing of each strategy is assessed, with times ranging from 12 h (FFF) to 61 h (hybridization of FFF and SLS), as labor times differ significantly. Cost per model variation is also significant, ranging from EUR 80 (FFF) to EUR 600 (MJ). The main limitation is the mimicry of physiological properties. Viscoelastic properties and the combination of materials, colors and textures are also substantially different according to the strategy and the intended use. It was concluded that MJ is the best overall option, although its use in hospitals is limited due to its cost. Consequently, indirect 3D printing could be a solid and cheaper alternative.

Brain correlates of speech perception in schizophrenia patients with and without auditory hallucinations.

The experience of auditory verbal hallucinations (AVH, "hearing voices") in schizophrenia has been found to be associated with reduced auditory cortex activation during perception of real auditory stimuli like tones and speech. We re-examined this finding using 46 patients with schizophrenia (23 with frequent AVH and 23 hallucination-free), who underwent fMRI scanning while they heard words, sentences and reversed speech. Twenty-five matched healthy controls were also examined. Perception of words, sentences and reversed speech all elicited activation of the bilateral superior temporal cortex, the inferior and lateral prefrontal cortex, the inferior parietal cortex and the supplementary motor area in the patients and the healthy controls. During the sentence and reversed speech conditions, the schizophrenia patients as a group showed reduced activation in the left primary auditory cortex (Heschl's gyrus) relative to the healthy controls. No differences were found between the patients with and without hallucinations in any condition. This study therefore fails to support previous findings that experience of AVH attenuates speech-perception-related brain activations in the auditory cortex. At the same time, it suggests that schizophrenia patients, regardless of presence of AVH, show reduced activation in the primary auditory cortex during speech perception, a finding which could reflect an early information processing deficit in the disorder.

Negative schizophrenic symptoms as prefrontal cortex dysfunction: Examination using a task measuring goal neglect.

BACKGROUND: The negative symptoms of schizophrenia have been proposed to reflect prefrontal cortex dysfunction. However, this proposal has not been consistently supported in functional imaging studies, which have also used executive tasks that may not capture key aspects of negative symptoms such as lack of volition. METHOD: Twenty-four DSM-5 schizophrenic patients with high negative symptoms (HNS), 25 with absent negative symptoms (ANS) and 30 healthy controls underwent fMRI during performance of the Computerized Multiple Elements Test (CMET), a task designed to measure poor organization of goal directed behaviour or 'goal neglect'. Negative symptoms were rated using the PANSS and the Clinical Assessment Interview for Negative Symptoms (CAINS). RESULTS: On whole brain analysis, the ANS patients showed no significant clusters of reduced activation compared to the healthy controls. In contrast, the HNS patients showed hypoactivation compared to the healthy controls in the left anterior frontal cortex, the right dorsolateral prefrontal cortex (DLPFC), the anterior insula bilaterally and the bilateral inferior parietal cortex. When compared to the ANS patients, the HNS patients showed reduced activation in the left anterior frontal cortex, the left DLPFC and the left inferior parietal cortex. After controlling for disorganization scores, differences remained in clusters in the left anterior frontal cortex and the bilateral inferior parietal cortex. CONCLUSIONS: This study provides evidence that reduced prefrontal activation, perhaps especially in the left anterior frontal cortex, is a brain functional correlate of negative symptoms in schizophrenia. The simultaneous finding of reduced inferior parietal cortex activation was unexpected, but could reflect this region's involvement in cognitive control, particularly the 'regulative' component of this.

Regularized Functional Connectivity in Schizophrenia.

Regularization may be used as an alternative to dimensionality reduction when the number of variables in a model is much larger than the number of available observations. In a recent study from our group regularized regression was employed to quantify brain functional connectivity in a sample of healthy controls using a brain parcellation and resting state fMRI images. Here regularization is applied to evaluate resting state connectivity abnormalities at the voxel level in a sample of patients with schizophrenia. Specifically, ridge regression is implemented with different degrees of regularization. Results are compared to those delivered by the weighted global brain connectivity method (GBC), which is based on averaged bivariate correlations and from the non-redundant connectivity method (NRC), a dimensionality reduction approach that applies supervised principal component regressions. Ridge regression is able to detect a larger set of abnormally connected regions than both GBC and NRC methods, including schizophrenia related connectivity reductions in fronto-medial, somatosensory and occipital structures. Due to its multivariate nature, the proposed method is much more sensitive to group abnormalities than the GBC, but it also outperforms the NRC, which is multivariate too. Voxel based regularized regression is a simple and sensitive alternative for quantifying brain functional connectivity.

Processing of linguistic deixis in people with schizophrenia, with and without auditory verbal hallucinations.

Auditory verbal hallucinations (AVH) are a key symptom of schizophrenia (SZ) defined by anomalous perception of speech. Anomalies of processing external speech stimuli have also been reported in people with AVH, but it is unexplored which specific dimensions of language are processed differently. Using a speech perception task (passive listening), we here targeted the processing of deixis, a key dimension of language governing the contextual anchoring of speech in interpersonal context. We designed naturalistic speech stimuli that were either non-personal and fact-reporting ('low-deixis' condition), or else involved rich deictic devices such as the grammatical first and second persons, direct questions, and vocatives ('high-deixis'). We asked whether neural correlates of deixis obtained with fMRI would distinguish patients with and without frequent hallucinations (AVH + vs AVH-) from controls and each other. Results showed that high-deixis relative to low-deixis was associated with clusters of increased activation in the bilateral middle temporal gyri extending into the temporal poles and the inferior parietal cortex, in all groups. The AVH + and AVH- groups did not differ. When unifying them, the SZ group as a whole showed altered activity in the precuneus, midline regions and inferior parietal cortex. These results fail to confirm deictic processing anomalies specific to patients with AVH, but reveal such anomalies across SZ. Hypoactivation of this network may relate to a cognitive mechanism for attributing and anchoring thought and referential speech content in context.

Robot-assisted, real-time, MRI-guided laser interstitial thermal therapy for pediatric patients with hypothalamic hamartoma: surgical technique, pitfalls, and initial results.

OBJECTIVE: Real-time, MRI-guided laser interstitial thermal therapy (MRgLITT) has been reported as a safe and effective technique for the treatment of epileptogenic foci in children and adults. After the recent approval of MRgLITT by the European Medicines Agency in April 2018, the authors began to use it for the treatment of hypothalamic hamartomas (HHs) in pediatric patients with the assistance of a robotic arm. In this study, the authors report their initial experience describing the surgical technique, accuracy of the robotic arm, safety, and efficacy. METHODS: The laser fiber was placed with the assistance of the stereotactic robotic arm. The accuracy of the robotic arm for this procedure was calculated by comparing the intraoperative MRI to the preoperative plan. Common demographic and seizure characteristics of the patients, laser ablation details, complications, and short-term seizure outcomes were prospectively collected. RESULTS: Sixteen procedures (11 first ablations and 5 reablations) were performed in 11 patients between 15 months and 17 years of age (mean age 6.4 years) with drug-resistant epilepsy related to HHs. The mean target point localization error was 1.69 mm. No laser fiber needed to be repositioned. The mean laser power used per procedure was 4.29 W. The trajectory of the laser fiber was accidentally ablated in 2 patients, provoking transient hemiparesis in one of these patients. One patient experienced postoperative somnolence and syndrome of inappropriate antidiuretic hormone secretion, and 2 patients had transient oculomotor (cranial nerve III) palsy. Fifty-four percent of the patients were seizure free after the first ablation (mean follow-up 22 months, range 15-33 months). All 5 patients who experienced an epilepsy relapse underwent a second treatment, and 4 remain seizure free at least 5 months after reablation. CONCLUSIONS: In the authors' experience, the robotic arm was sufficiently accurate for laser fiber insertion, even in very young patients. MRgLITT appears to be an effective treatment for selected cases of HH. MRgLITT for HH is a minimally invasive procedure with appealing safety features, as it allows delivery of energy precisely under real-time MRI control. Nonetheless, complications may occur, especially in voluminous HHs. The amount of delivered energy and the catheter cooling system must be closely monitored during the procedure. A larger sample size and longer follow-up duration are needed to judge the efficacy and safety of MRgLITT for HH more rigorously. This initial experience was very promising.

Study protocol for a randomised, double-blinded, placebo-controlled phase III trial examining the add-on efficacy, cost-utility and neurobiological effects of low-dose naltrexone (LDN) in patients with fibromyalgia (INNOVA study).

INTRODUCTION: There is evidence that low-dose naltrexone (LDN; <5.0 mg/day) reduces pain and improves the quality of life of people with fibromyalgia syndrome (FMS). However, no randomised controlled trials with long-term follow-ups have been carried out. The INNOVA study will evaluate the add-on efficacy, safety, cost-utility and neurobiological effects of LDN for reducing pain in patients with FMS, with a 1-year follow-up. METHODS AND ANALYSIS: A single-site, prospective, randomised, double-blinded, placebo-controlled, parallel design phase III trial will be performed. Eligibility criteria include being adult, having a diagnosis of FMS and experiencing pain of 4 or higher on a 10-point numerical rating scale. Participants will be randomised to a LDN intervention group (4.5 mg/day) or to a placebo control group. Clinical assessments will be performed at baseline (T0), 3 months (T1), 6 months (T2) and 12 months (T3). The primary endpoint will be pain intensity. A sample size of 60 patients per study arm (120 in total), as calculated prior to recruitment for sufficient power, will be monitored between January 2022 and August 2024. Assessment will also include daily ecological momentary evaluations of FMS-related symptoms (eg, pain intensity, fatigue and sleep disturbance), and side effects via ecological momentary assessment through the Pain Monitor app during the first 3 months. Costs and quality-adjusted life years will be also calculated. Half of the participants in each arm will be scanned with MRI at T0 and T1 for changes in brain metabolites related to neuroinflammation and central sensitisation. Inflammatory biomarkers in serum will also be measured. ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee of the Fundació Sant Joan de Déu. The results will be actively disseminated through peer-reviewed journals, conference presentations, social media and community engagement activities. TRIAL REGISTRATION NUMBER: NCT04739995.

3D surgical planning of pediatric tumors: a review.

BACKGROUND: 3D surgical planning for the treatment of tumors in pediatrics using different neuroimaging methods is witnessing an accelerating and dynamic development. Until now, there have been many reports on the use of 3D printing techniques in different aspects of medical practice. Pediatric tumors mainly in the abdomen are among the most medical specialties that benefit from using this technique. The purpose of the current study is to review published literature regarding 3D surgical planning and its applications in the treatment of pediatric tumors and present challenges facing these techniques. MATERIALS AND METHODS: A completed review of the available literature was performed, effect sizes from published studies were investigated, and results are presented concerning the use of 3D surgical planning in the management of pediatric tumors, most of which are abdominal. RESULTS: According to the reviewed literature, our study comes to the point that 3D printing is a valuable technique for planning surgery for pediatric tumors in heart, brain, abdomen and bone. MRI and CT are the most common used techniques for preparing 3D printing models, as indicated by the reviewed reports. The reported studies have indicated that 3D printing allows the understanding of the anatomy of complex tumor cases, the simulation using surgical instruments, and medical and family education. The materials, 3D printing techniques and costs to be used depend on the application. CONCLUSION: This technology can be applied in clinical practice with a wide spectrum, using various tools and a range of available 3D printing methods. Incorporating 3D printing into an effective application can be a gratifying process with the use of a multidisciplinary team and rapid advances, so more experience would be needed with this technique to show a clinical gain.