Academic outcomes before and after clinical onset of acquired demyelinating syndromes in children: a matched cohort data linkage study.

It is unknown if cognition is impaired before clinical onset of paediatric acquired demyelinating syndromes. We conducted a matched cohort study using prospectively collected educational data in multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD) patients (n = 60) and controls (pooled n = 449,553). Academic performance at ages 10-11 was impaired in MOGAD (-1.27 adjusted z-score [95% CI: -1.81 to -0.73], P < 0.001) and preclinical MS (-0.40 [-0.80 to -0.0003], P = 0.0498). Moderate/high-efficacy MS treatment was associated with better final academic performance (0.92 [0.28-1.57], P = 0.005). After clinical onset MS patients missed 8.7% of school (controls 2.9%, P < 0.001) and MOGAD patients 11.9% (controls 2.0%, P < 0.001).

Pediatric MOG-Ab-Associated Encephalitis: Supporting Early Recognition and Treatment.

BACKGROUND AND OBJECTIVES: Antibodies to myelin oligodendrocyte glycoprotein (MOG-Ab) have recently been reported in patients with encephalitis who do not fulfill criteria for acute disseminated encephalomyelitis (ADEM). We evaluated a cohort of these children and compared them with children with ADEM. METHODS: This retrospective, multicenter cohort study comprised consecutive patients <18 years of age with MOG-Ab who fulfilled criteria for autoimmune encephalitis. These patients were stratified into (1) children not fulfilling criteria for ADEM (encephalitis phenotype) and (2) children with ADEM. Clinical/paraclinical data were extracted from the electronic records. Comparisons were made using the Mann-Whitney U test and χ2 Fisher exact test for statistical analysis. RESULTS: From 235 patients with positive MOG-Ab, we identified 33 (14%) with encephalitis and 74 (31%) with ADEM. The most common presenting symptoms in children with encephalitis were headache (88%), seizures (73%), and fever (67%). Infective meningoencephalitis was the initial diagnosis in 67%. CSF pleocytosis was seen in 79%. Initial MRI brain was normal in 8/33 (24%) patients. When abnormal, multifocal cortical changes were seen in 66% and unilateral cortical changes in 18%. Restricted diffusion was demonstrated in 43%. Intra-attack new lesions were seen in 7/13 (54%). When comparing with children with ADEM, children with encephalitis were older (median 8.9 vs 5.7 years, p = 0.005), were more likely to be admitted to intensive care (14/34 vs 4/74, p < 0.0001), were given steroid later (median 16.6 vs 9.6 days, p = 0.04), and were more likely to be diagnosed with epilepsy at last follow-up (6/33 vs 1/74, p = 0.003). DISCUSSION: MOG-Ab should be tested in all patients with suspected encephalitis even in the context of initially normal brain MRI. Although exclusion of infections should be part of the diagnostic process of any child with encephalitis, in immunocompetent children, when herpes simplex virus CSF PCR and gram stains are negative, these features do not preclude the diagnosis of immune mediated disease and should not delay initiation of first-line immunosuppression (steroids, IVIG, plasma exchange), even while awaiting the antibody results.

The prognostic utility of the neutrophil to lymphocyte ratio in paediatric brain tumours: a retrospective case control study.

INTRODUCTION: Paediatric brain tumours (PBT) are the most common cause of death among all childhood cancers. The neutrophil to lymphocyte ratio (NLR) has been shown to prognosticate many adult cancers. There is a paucity of literature on the NLR in PBTs. This study aims to study the link between PBTs and the NLR by comparing the preoperative serum NLR in children under 16 with brain tumours with their outcome in terms of grade of brain tumour and overall survival. METHODS: This is a retrospective case control study. The NLRs were compared between patients with benign or malignant PBTs and patients who were alive or dead. Receiver-operating characteristic (ROC) curve analyses were performed and Youden indexes were calculated to evaluate the predictive potential of the NLR. A cut-off point of NLR > 4 was selected for the calculation of odds ratios. RESULTS: A total of 515 patients were included in this study. 53.8% were male. 66.2% had benign PBTs. 81.0% were alive at the time of the study. Patients with malignant PBTs had a higher NLR compared to patients with benign PBTs (p = 0.0066**). There was no difference in the NLR between patients who were dead compared to those who were alive (p = 0.1682 ns). The NLR had a Youden's index of 0.1567 to predict malignant PBTs and 0.1285 to predict survival. CONCLUSION: A high NLR was associated with an increased odds of having a malignant PBT but a reliable cut-off point was not identified and the underlying mechanisms for this remain unknown. The NLR is a poor diagnostic biomarker due to its poor overall sensitivity and specificity. More research is required to further study the role of immunity in PBTs.

Consumer preference and willingness-to-pay for formal recycling of electric vehicle batteries: A discrete choice experiment in China.

The burgeoning electric vehicle (EV) market poses a substantial challenge to battery recycling systems, yet understanding EV battery recycling behavior from the demand side remains limited. Previous studies have analyzed perceptual or attitudinal factors, neglecting the observable attributes of EV battery recycling. To this end, we proposed a discrete choice model to investigate the differences between formal and informal recycling behaviors, identifying consumer preferences and willingness to pay. By analyzing 1190 sample data collected from Chongqing, China, we find that: (1) The formal recycling market exhibits greater sensitivity to prices compared to the informal recycling market. (2) The formal recycling market favors recycling by EV battery producers, whereas the informal recycling market shows the least preference for recycling by automobile producers. (3) Door-to-door recycling services are the most effective in facilitating the transition from informal to formal recycling markets for EV batteries. (4) Capacity subsidy policies outperform one-time fixed subsidy policies in incentivizing formal recycling. (5) The formal recycling market for EV batteries necessitates "traceability to the recycling outlet", as opposed to being untraceable. (6) The high-awareness group exhibits greater sensitivity to government policies compared to those with lower environmental concerns and less knowledge of EV battery recycling.

The management of liver disease in people with congenital bleeding disorders: guidance from European Association for Haemophilia and Allied Disorders, European Haemophilia Consortium, ISTH, and World Federation of Hemophilia.

People with bleeding disorders (PWBD) have been exposed to the risk of developing chronic viral hepatitis and cirrhosis after replacement therapy. Today, the advent of new pharmacologic strategies for the control of hemostasis and the efficacious antiviral therapies against hepatitis C virus and hepatitis B virus have significantly reduced this risk. However, the definitive success for liver health in this clinical setting is also influenced by other factors, such as the severity of liver disease at the time of hepatitis B virus/hepatitis C virus antiviral therapy and the exposure to highly prevalent factors of chronic liver damage (eg, metabolic dysfunction and/or alcohol) that can cause a residual risk of complications such as hepatocellular carcinoma, portal hypertension, and liver insufficiency. With this background, a group of experts selected among hepatologists, hematologists, PWBD treaters, and patient representatives produced this practical multisociety guidance for the protection of liver health and the prevention and management of liver complications in PWBD based on the most updated protocols of care.

Cancer-Associated Venous Thromboembolic Disease, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology.

The NCCN Guidelines for Cancer-Associated Venous Thromboembolic Disease provide strategies for the prevention, diagnosis, and treatment of venous thromboembolism (VTE) in adult patients with cancer. VTE is a common and life-threatening condition in patients with cancer, and its management often requires multidisciplinary efforts. The NCCN panel is comprised of specialists spanning various fields, including cardiology, hematology, medical oncology, internal medicine, interventional radiology, and pharmacology. The content featured in this issue specifically addresses the evaluation and recommended treatment options outlined in the NCCN Guidelines for the diverse subtypes of cancer-associated VTE.

Targeted Treatments for Myasthenia Gravis in Children and Adolescents.

Myasthenia gravis (MG) is an antibody-mediated disorder of the neuromuscular junction affecting children and adults. MG is a treatable condition with most patients requiring immunosuppression for disease control and/or remission. Juvenile myasthenia gravis (JMG) is rare in comparison with adult-onset MG but given the same underlying pathophysiology, treatment strategies are similar to those in adults. Until recently, there were only a few randomised controlled trials (RCTs) for MG treatments in adults and none in children, and management strategies were primarily based on expert consensus. In addition, treatment options for refractory MG cases have been severely limited, resulting in poor long-term quality of life in such patients due to the significant disease burden. Recently, there have been several RCTs focussing on novel therapeutic strategies with potentially promising outcomes, suggesting a change in MG management over the coming years and access to more effective and faster-acting drugs for MG patients. This paper will review current and new MG treatments including efgartigimod, eculizumab, rozanolixizumab, ravulizumab, and zilucoplan, with a focus on juvenile myasthenia gravis.

International consensus definitions for infection-triggered encephalopathy syndromes.

AIM: To develop standardized diagnostic criteria for 'infection-triggered encephalopathy syndrome (ITES)' and five specific clinical syndromes of ITES. METHOD: The draft definitions were based on existing criteria, standardized, and discussed by a panel of international experts using nominal group technique over 18 months to achieve consensus. All criteria use the same format: (1) presence of infection/fever; (2) clinical features including encephalopathy; (3) neuroradiological features on magnetic resonance imaging; (4) exclusion of other causes. RESULTS: We first highlighted differences between ITES and infectious and autoimmune encephalitis, which is the most important differential diagnosis. Consensus was achieved to define five specific ITESs: acute encephalopathy with biphasic seizures and late reduced diffusion; acute necrotizing encephalopathy; mild encephalopathy with a reversible splenial lesion; acute fulminant cerebral oedema; and acute shock with encephalopathy and multiorgan failure. Two further conditions that are currently classified as epilepsy syndromes but have similar features to ITES, namely febrile infection-related epilepsy syndrome and hemiconvulsion-hemiplegia-epilepsy syndrome, are also discussed. INTERPRETATION: The consensus definition is expected to improve awareness of this disease concept, provide diagnostic framework, and facilitate future international research and clinical trials.

Long term outcome in non-multiple sclerosis paediatric acquired demyelinating syndromes.

OBJECTIVES: We aimed to study the risks of relapse and long term disability in children with non-MS acquired demyelinating syndromes (ADS). METHODS: In this prospective, multi-centre study, from the 14 UK pediatric neurology centres, children (<16 years) experiencing a first episode of ADS were recruited from 2010 to 2014. Case report forms were collected prospectively. RESULTS: A total of 269 children were recruited and followed up for a median of 7.2 years. Median age at onset was 9y (IQR 9.5-14.5, 126 females). At last follow-up, 46 (18 %) had MS, 4 AQP4-Ab NMOSD and 206 (80 %) had other ADS, of which 27 (13 %) relapsed. Relapsing MOGAD was the diagnosis in 12/27, 6 were seronegative and 9 did not have antibodies tested. Frequency of relapse differed according to first presentation in non-MS ADS, being least likely in transverse myelitis (p = 0.025). In the non-MS group, MOG-Ab was predictive of relapse (HR = 8.42; p < 0.001) occurring 8 times as often decreasing over time. Long-term difficulties did not differ between children with monophasic vs relapsing diseases. CONCLUSION: The risk of relapse in non-MS ADS depends on initial diagnosis, and MOG-Ab positivity. Long-term difficulties are observed regardless of relapses and are determined by presenting phenotype.

UK research priority setting for childhood neurological conditions.

AIM: To identify research priorities regarding the effectiveness of interventions for children and young people (CYP) with childhood neurological conditions (CNCs). These include common conditions such as epilepsies and cerebral palsy, as well as many rare conditions. METHOD: The National Institute for Health and Care Research (NIHR) and the James Lind Alliance (JLA) champion and facilitate priority setting partnerships (PSPs) between patients, caregivers, and clinicians (stakeholders) to identify the most important unanswered questions for research (uncertainties). A NIHR-JLA and British Paediatric Neurology Association collaboration used the JLA PSP methodology. This consisted of two surveys to stakeholders: survey 1 (to identify uncertainties) and survey 2 (a prioritization survey). The final top 10 priorities were agreed by consensus in a stakeholder workshop. RESULTS: One hundred and thirty-two charities and partner organizations were invited to participate. In survey 1, 701 participants (70% non-clinicians, including CYP and parent and caregivers) submitted 1800 uncertainties from which 44 uncertainties were identified for prioritization in survey 2; from these, 1451 participants (83% non-clinicians) selected their top 10 priorities. An unweighted amalgamated score across participant roles was used to select 26. In the final workshop, 14 health care professionals, 11 parent and caregivers, and two CYP ranked the 26 questions to finalize the top 10 priorities. Ten top priority questions were identified regarding interventions to treat CYP with CNCs and their associated comorbidities, for example, sleep, emotional well-being, and distressing symptoms. INTERPRETATION: The results of this study will inform research into the effectiveness of interventions for children with neurological conditions.

Perioperative Recommendations for Corneal Refractive Surgery Patients With Inherited Bleeding Disorders.

PURPOSE: To synthesize the current literature regarding patients with inherited bleeding disorders and suggest comprehensive evaluation and preoperative recommendations for these patients before undergoing corneal refractive surgery. METHODS: The literature search was conducted through PubMed, Embase, and Google Scholar databases for publications through January 4, 2024 for reports of ocular bleeding manifestations in patients with inherited bleeding disorders and reports of patients without a history of bleeding disorders who had intraoperative or postoperative hemorrhagic complications with corneal refractive surgery. Additional cases from the literature and a retrospective chart review at a corneal practice were obtained describing patients with inherited bleeding disorders who underwent corneal refractive surgery. RESULTS: Four articles were found detailing ocular bleeding manifestations in patients with inherited bleeding disorders who underwent ocular surgery other than corneal refractive surgery. Thirty articles were found detailing intraoperative and postoperative bleeding manifestations in patients without a history of inherited bleeding disorders who underwent corneal refractive surgery. Eight cases (3 patients from the literature search and 5 patients from a retrospective chart review) were found regarding patients with inherited bleeding disorders who underwent corneal refractive surgery. CONCLUSIONS: For corneal refractive surgery with topical anesthesia, the perioperative risk and need for any hemostasis intervention in individuals with an inherited bleeding disorder depends on the type of disorder, status of preoperative factor level concentrations, or a prior history of bleeding. If required, clotting factor optimization should be tailored to each candidate on a case-by-case basis.

Intrathyroidal thymic carcinoma.

A young woman in her early 30s presented with a right thyroid mass and progressive hoarseness due to a right vocal cord palsy. The preoperative fine-needle aspiration cytology was classified as Bethesda V and she underwent a total thyroidectomy and neck dissection. Intraoperatively, the thyroid mass was adherent to the oesophagus, trachea and encasing the right recurrent laryngeal nerve which was sacrificed. Final histopathology diagnosed a rare subtype of thyroid cancer known as intrathyroidal thymic carcinoma (ITC). She was then sent for adjuvant radiotherapy after a multidisciplinary tumour board discussion. This case report highlights the difficulty in preoperative diagnosis of ITC and the importance of immunohistochemical staining in clinching the diagnosis. In view of its rarity, there have been no published consensus on the treatment of ITC, hence we would like to share some learning points through a comprehensive literature review.

Evidence-Based Physiotherapeutic Interventions Enhancing Hand Dexterity, Activities of Daily Living and Quality of Life of Parkinson's Disease Patients: A Systematic Review.

OBJECTIVES: This systematic review primarily aims to identify the optimal physiotherapeutic intervention to improve hand dexterity in Parkinson's Disease (PD) patients. The secondary objectives were to identify the hand dexterity physiotherapeutic interventions available for PD patients, and to determine the quality of these interventions. REVIEW METHODS: Eight electronic databases were systematically searched to identify relevant randomized controlled trial full-text articles using the established search strategy. The primary outcomes of interest were measurements for hand dexterity and activities of daily living (ADL). RESULTS: A total of 11 studies comprising 647 participants with PD were included. Most studies had a high risk of performance bias and an unclear risk of selection bias. The intervention training period ranged from a single session to 12 weeks. Compared to their respective control group, eight out of 11 studies revealed significant results in hand dexterity, two out of three studies reported positive effects on ADL, four of seven studies showed significant improvements in upper limb motor performance, and two studies perceived positive benefits in terms of overall quality of life. Five out of 11 studies that recorded the occurrence of adverse events reported no adverse events post-intervention. CONCLUSION: The dearth of evidence made it difficult to support any one intervention as the best intervention when compared to the other PD treatments in upper limb rehabilitation. Regardless, a home-based dexterity rehabilitation programme is still a promising approach to enhance dexterity-related functional abilities.

Progressive Cheek Swelling in an Older Woman.

An 87-year-old woman presents with sudden-onset worsening right facial swelling and pain and generalized maxillary alveolar hyperplasia. What is your diagnosis?

Treatments and Outcomes Among Patients with Sydenham Chorea: A Meta-Analysis.

Importance: Sydenham chorea is the most common acquired chorea of childhood worldwide; however, treatment is limited by a lack of high-quality evidence. Objectives: To evaluate historical changes in the clinical characteristics of Sydenham chorea and identify clinical and treatment factors at disease onset associated with chorea duration, relapsing disease course, and functional outcome. Data Sources: The systematic search for this meta-analysis was conducted in PubMed, Embase, CINAHL, Cochrane Library, and LILACS databases and registers of clinical trials from inception to November 1, 2022 (search terms: [Sydenham OR Sydenham's OR rheumatic OR minor] AND chorea). Study Selection: Published articles that included patients with a final diagnosis of Sydenham chorea (in selected languages). Data Extraction and Synthesis: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Individual patient data on clinical characteristics, treatments, chorea duration, relapse, and final outcome were extracted. Data from patients in the modern era (1945 through 2022) were entered into multivariable models and stratified by corticosteroid duration for survival analysis of chorea duration. Main Outcomes and Measures: The planned study outcomes were chorea duration at onset, monophasic course (absence of relapse after ≥24 months), and functional outcome (poor: modified Rankin Scale score 2-6 or persisting chorea, psychiatric, or behavioral symptoms at final follow-up after ≥6 months; good: modified Rankin Scale score 0-1 and no chorea, psychiatric, or behavioral symptoms at final follow-up). Results: In total, 1479 patients were included (from 307 articles), 1325 since 1945 (median [IQR] age at onset, 10 [8-13] years; 875 of 1272 female [68.8%]). Immunotherapy was associated with shorter chorea duration (hazard ratio for chorea resolution, 1.51 [95% CI, 1.05-2.19]; P = .03). The median chorea duration in patients receiving 1 or more months of corticosteroids was 1.2 months (95% CI, 1.2-2.0) vs 2.8 months (95% CI, 2.0-3.0) for patients receiving none (P = .004). Treatment factors associated with monophasic disease course were antibiotics (odds ratio [OR] for relapse, 0.28 [95% CI, 0.09-0.85]; P = .02), corticosteroids (OR, 0.32 [95% CI, 0.15-0.67]; P = .003), and sodium valproate (OR, 0.33 [95% CI, 0.15-0.71]; P = .004). Patients receiving at least 1 month of corticosteroids had significantly lower odds of relapsing course (OR, 0.10 [95% CI, 0.04-0.25]; P < .001). No treatment factor was associated with good functional outcome. Conclusions and Relevance: In this meta-analysis of treatments and outcomes in patients with Sydenham chorea, immunotherapy, in particular corticosteroid treatment, was associated with faster resolution of chorea. Antibiotics, corticosteroids and sodium valproate were associated with a monophasic disease course. This synthesis of retrospective data should support the development of evidence-based treatment guidelines for patients with Sydenham chorea.

A machine learning approach to predict mortality due to immune-mediated thrombotic thrombocytopenic purpura.

Background: Mortality due to immune-mediated thrombotic thrombocytopenic purpura (iTTP) remains significant. Predicting mortality risk may potentially help individualize treatment. The French Thrombotic Microangiopathy (TMA) Reference Score has not been externally validated in the United States. Recent advances in machine learning technology can help analyze large numbers of variables with complex interactions for the development of prediction models. Objectives: To validate the French TMA Reference Score in the United States Thrombotic Microangiopathy (USTMA) iTTP database and subsequently develop a novel mortality prediction tool, the USTMA TTP Mortality Index. Methods: We analyzed variables available at the time of initial presentation, including demographics, symptoms, and laboratory findings. We developed our model using gradient boosting machine, a machine learning ensemble method based on classification trees, implemented in the R package gbm. Results: In our cohort (n = 419), the French score predicted mortality with an area under the receiver operating characteristic curve of 0.63 (95% CI: 0.50-0.77), sensitivity of 0.35, and specificity of 0.84. Our gradient boosting machine model selected 8 variables to predict acute mortality with a cross-validated area under the receiver operating characteristic curve of 0.77 (95% CI: 0.71-0.82). The 2 cutoffs corresponded to sensitivities of 0.64 and 0.50 and specificities of 0.76 and 0.87, respectively. Conclusion: The USTMA Mortality Index was acceptable for predicting mortality due to acute iTTP in the USTMA registry, but not sensitive enough to rule out death. Identifying patients at high risk of iTTP-related mortality may help individualize care and ultimately improve iTTP survival outcomes. Further studies are needed to provide external validation. Our model is one of many recent examples where machine learning models may show promise in clinical prediction tools in healthcare.