Duccio Maria Cordelli

Summary: Posterior reversible encephalopathy syndrome (PRES) is a rare but potentially life‐threatening neurological complication following paediatric allogeneic haematopoietic stem cell transplantation (HSCT). Its heterogeneous presentation and the absence of standardized guidance contribute to variability in diagnosis and management. The aim was to develop multidisciplinary, consensus‐based recommendations for the diagnosis, management and follow‐up of PRES in paediatric allogeneic HSCT recipients. A modified Delphi process was conducted between February and September 2025. An international panel comprising transplant physicians, neurologists, neuro‐oncologists and neuroradiologists participated in four iterative rounds. A systematic literature review informed statement development across five domains: pathogenesis, clinical features, diagnostics, management and follow‐up. Predefined agreement thresholds determined consensus. Thirty‐eight statements achieved consensus in the first round, indicating strong agreement. Key recommendations addressed risk factors, early clinical recognition, appropriate neuroimaging and management of contributory factors including hypertension and immunosuppressive therapy. Emphasis was placed on multidisciplinary care, prompt diagnosis and tailored management. Guidance on neurological monitoring and long‐term follow‐up was also established. These consensus recommendations provide a standardized framework for the management of PRES in paediatric allogeneic HSCT recipients. Their implementation may improve early recognition, optimize treatment and enhance outcomes, while highlighting priorities for future research and prospective guideline development.

Background: Advances in pediatric care have increased the survival of children with life-limiting conditions, leading to a growing population requiring pediatric palliative care (PPC). Respiratory tract infections are among the leading causes of hospitalization in these patients. This study aimed to describe the features of respiratory infections in children eligible for PPC. Methods: The present study is a monocentric retrospective study including pediatric patients eligible for PPC with an Assessment of Complex Clinical-Care Needs in Pediatrics (ACCAPED) score ≥30 who were followed by a third-level hospital in Bologna, Italy. Hospitalizations for respiratory infections occurring between January 2019 and February 2025 were analyzed. Clinical, microbiologic, laboratory and therapeutic data were collected. Results: Among 319 eligible PPC patients, 99 experienced at least 1 infectious hospitalization, accounting for 117 admissions due to respiratory infections in 56 children. Lower respiratory tract infections predominated (86.3%), with viral pathogens identified in most cases. Respiratory support required escalation in 76.9% of admissions, while 6% required pediatric intensive care, and mortality was 1.7%. Pseudomonas aeruginosa was the most frequently isolated bacterial pathogen, especially among tracheostomized patients. Multivariate analysis identified an Assessment of Complex Clinical-Care Needs in Pediatrics score ≥75 [odds ratio (OR): 2.43; 95% confidence interval (CI): 1.04–5.68; P = 0.041] and C-reactive protein ≥8 mg/dL (OR: 3.85; 95% CI: 1.48–10.00; P = 0.0058) as independent predictors of respiratory support escalation. Conclusions: Respiratory infections represent a major cause of hospitalization in children receiving PPC. High clinical complexity and elevated inflammatory markers independently predict worsening respiratory status, supporting their use for early risk stratification and individualized management.

Background and ObjectivesAntibody testing has a pivotal role in the diagnosis of myasthenia gravis (MG). However, there are limited data on the accuracy of the different methods available for acety...

Myasthenia gravis (MG) is an autoimmune disorder primarily caused by antibodies targeting neuromuscular junction proteins, particularly the acetylcholine receptor and the muscle-specific tyrosine kinase. However, 10%-20% of patients with MG are double-seronegative (dsMG). Antibodies against low-density lipoprotein receptor-related protein 4 (LRP4-IgG) have been found in a variable proportion of dsMG cases, but their frequency and clinical relevance remain unclear because of differences in assay methodologies and study populations. In this study, we assessed the frequency of LRP4-IgG in patients with suspected MG using different cell-based assay (CBA) protocols. In this multicenter observational study, we enrolled consecutive patients presenting with symptoms suggestive of MG. LRP4-IgG was tested by 2 centers using 3 different CBAs: live (l-CBA), methanol-fixed (mf-CBA), and paraformaldehyde-fixed (pf-CBA). Patients were classified as having MG or other disorders (ODs). Positive samples were cross-tested between centers. Among 684 patients (302 with MG, 382 with ODs), LRP4-IgG was detected by mf-CBA in 2% (6/302) of MG cases and in 0.52% (2/382) of OD cases. Among patients with MG, 3.9% (4/102) of dsMG and 1% (2/200) of seropositive patients tested positive. Only 50% of mf-CBA-positive cases were confirmed by pf-CBA, and none were detected by l-CBA. Cross-center testing showed partial reproducibility. LRP4-IgG detection in suspected MG is rare and inconsistent across assays, suggesting that routine testing is not currently warranted and that these antibodies are at present of limited diagnostic value. These findings highlight the need for standardized, validated LRP4-IgG assays. Future studies should focus on direct comparison and harmonization of testing protocols to clarify the clinical utility of LRP4-IgG testing.

Genetic factors are major contributors to pediatric epilepsy, but their role in status epilepticus (SE) remains incompletely defined. We aimed to characterize the clinical and genetic landscape of pediatric epilepsy complicated by SE in a large cohort, and to identify clinical features associated with genetic etiologies. We conducted a retrospective, multicenter, exploratory cohort study by selecting patients aged 1 month-18 years who experienced SE from the Italian Pediatric Status Epilepticus (IPSE) group database (2010-2022). SE and epilepsy syndromes were defined according to International League Against Epilepsy criteria. From the IPSE dataset, we included only patients with epilepsy whose etiology was classified as genetic (confirmed or presumed) or nongenetic (lesional, autoimmune, metabolic-acquired, infectious, or unknown). Clinical data were collected using standardized electronic case report forms. Of 1,071 children in the IPSE cohort, 790 with SE and epilepsy were included (median age at SE onset 3.9 years, interquartile range 1.3-8.1; 44% female). A genetic etiology was confirmed or presumed in 519 (66%). Compared with those with nongenetic etiologies (n = 271), patients with genetic epilepsies presented with SE at a younger age (median 3.4 vs 4.8 years, q = 0.003) and more often had epilepsy with both focal and generalized seizures (31% vs 13%, q < 0.001). The underlying genetic abnormality was identified in 222 patients (42.7%) including 179 with confirmed single-gene pathogenic variants and 43 chromosomal alterations. Ion channel genes were most frequent (38%), with SCN1A variants accounting for 18% of confirmed single-gene cases. Neurodevelopmental and mTOR pathway genes were also frequent contributors. Logistic regression showed that younger age at SE (odds ratio [OR] 0.92, 95% CI 0.85-0.98, p = 0.020) and epilepsy with both focal and generalized seizures (OR 4.00, 95% CI 2.09-7.85, p < 0.001) were independently associated with channelopathies. In this large real-world cohort, two-thirds of children with epilepsy and SE had a genetic etiology, most commonly channelopathies. Younger age at SE and epilepsy with both focal and generalized seizure were linked to genetic causes. Despite limitations in testing strategies and retrospective design, these findings highlight the importance of systematic genetic investigation in pediatric epilepsies presenting SE.

Seizures, when prolonged or repeated, leading to status epilepticus (SE), represent a medical emergency, requiring prompt treatment. In these conditions, the use of continuous midazolam (MDZ) infusion is often reserved for established or refractory SE and considered an anesthesiologic treatment, while evidence on its early use in non‐intensive settings is still limited. To verify this approach in daily practice, we retrospectively collected data on about 42 episodes of pediatric SE or acute repetitive seizures (ARSs), treated with continuous MDZ infusion in non‐intensive setting. Collected data include demographical information, previous history of epilepsy, instrumental examinations (electroencephalography [EEG] and brain magnetic resonance imaging [MRI]), comorbidities, anti‐seizure medications (ASMs), information about the event, other treatments (first‐ and second‐line), information about MDZ infusion, and need for other third‐line treatment and/or intensive care unit (ICU) transfer. Infusion durations and rates varied widely, but in most cases (38/42) low dose (<.23 mg/kg/h) were employed. The treatment was effective in 84.2% of cases, achieving both clinical and EEG response. No adverse events (AEs) were reported. The need for a second‐line treatment (particularly levetiracetam [LEV] and phenobarbital [PB]) was associated with a worse outcome. Another third‐line treatment was needed in 9.5% of cases. Patients (21.4%) were transferred to ICU; a higher risk of ICU admission was reported in patients with precipitating factors (infection, surgery, hypertension and suboptimal anti‐seizure medication [ASM] serum levels), and those receiving MDZ infusion at higher rates and/or co‐treated with PB. Overall, our study suggests that low‐dose continuous MDZ infusion is an effective and safe strategy for treatment of pediatric SE and ARSs in non‐intensive settings.

This report details a pediatric case of myelin oligodendrocyte glycoprotein antibody disease (MOGAD) characterized by isolated MOG-IgG3 positivity and IgG1 deficiency, highlighting a unique serologic profile and exploring its immunologic significance. In addition, a review of MOGAD cases with isolated MOG-IgG3 antibodies is included. A 12-year-old boy presenting with a progressive neurologic syndrome underwent clinical, radiologic, and laboratory evaluation. MRI showed extensive brain and spinal lesions. MOG-IgG3 antibodies were identified in serum and CSF by live cell-based assay, while other MOG-IgG subclasses were not detected. Serum IgG1 was low at baseline and throughout follow-up. First-line immunotherapy treatment led to significant improvement, with no relapses at 2-year follow-up. This case highlights the potential role of subclinical IgG1 deficiency in shaping the predominance or selective detection of MOG-IgG3 in MOGAD. While most MOG antibodies are predominantly of the IgG1 isotype, our review identified a few cases with isolated MOG-IgG3 antibodies. A possible contribution to pathogenesis cannot be excluded, and the patient's inability to produce a balanced IgG subclass profile could have favored a sustained IgG3 response. Larger studies are needed to clarify the clinical significance of MOG-IgG3 in MOGAD.