Stefania Bergamoni

Background: Mild encephalopathy with reversible splenium lesion (MERS) is a clinical–radiologic entity characterized by a reversible lesion in the splenium of the corpus callosum, visible on magnetic resonance imaging (MRI) imaging, predominantly affecting children. Despite the unclear pathogenesis, some etiologies have been identified, with viral infections being the most common cause in children. Moreover, a minority of patients carry a genetic variant in the MYRF gene, which has been associated with reversible myelin vacuolization. Methods: Here we present 4 cases of pediatric MERS (age 2–10 years) admitted to Niguarda Hospital, Milan, Italy, in a time span of 13 months between December 2023 and January 2025. Results: Three patients exhibited MRI findings consistent with MERS type 1, involving only the splenial corpus callosum. The other one had a more severe clinical presentation, with stroke-like symptoms and a MERS type 2 MRI presentation, involving the white matter as well. In all of them, a viral etiology was identified (rotavirus, influenza A virus, human herpetic virus [HHV6]). Conclusions: We support the importance of early MRI in acute unexplained encephalopathy and suggest that genetic testing for MYRF variants should be reserved for selected cases with extensive white matter involvement.

Objective: The transition from pediatric to adult healthcare services is a particularly sensitive phase for young adults with chronic conditions, including epilepsy. In European countries, there is a lack of standardized protocols for an appropriate and detailed transition path. This study aimed to investigate the experiences of both patients and clinicians during the transition process to adulthood, with the goal of contributing to a nationwide consensus document to standardize practices across Italy. Methods: This multicentric, observational, prospective, qualitative study included interviews with young people who turned 18 between 2018 and 2022 belonging to four regional epilepsy centers. In addition, pediatric and adult neurologists completed questionnaires addressing epilepsy type, comorbidities, daily life impact, and details of the transition process. Results: Thirty‐seven patients (92.5%) participated in the study, 34 of them began the transition process, and the remaining three included two patients who continued to receive care within pediatric services and one patient who was lost to follow up. At the time of the interview, 30 (88%) patients were still under the care of the public adult service, while one returned to the pediatric service, one was followed by a private epileptologist, and two were not under any specialist care. The study revealed significant variability in the duration of the preparatory phase, the time elapsed between referral and access to adult services, and the methods of communication/reporting. The caregivers of patients with epilepsy and associated disabilities reported greater difficulty accessing referrals for multidisciplinary and specialized care for rare or complex epilepsies in adulthood. Significance: While most patients successfully transitioned, the absence of uniform, structured protocols, in particular for patients with disabilities, created a significant difference in managing transition. The study strongly underscores the urgent need for standardized, shared national guidelines to ensure a consistent, equitable, and effective transition from pediatric to adult epilepsy care across Italy.

Antibodies to proteolipid protein-1 (PLP1-IgG), a major central myelin protein also expressed in the peripheral nervous system (PNS) as the isoform DM20, have been previously identified mostly in patients with multiple sclerosis (MS), with unclear clinical implications. However, most studies relied on nonconformational immunoassays and included few patients with non-MS CNS autoimmune demyelinating disorders (ADDs). We aimed to investigate conformational PLP1-IgG in the whole ADD spectrum. We devised a new live cell-based assay (CBA) for PLP1-IgG and used it to test 2 cohorts (retrospective exploratory, n = 284; prospective validation, n = 824) of patients with ADDs and controls (n = 177). Patients were classified as MS, neuromyelitis optica spectrum disorders (NMOSDs), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and other ADDs. PLP1-IgG-positive samples were tested for IgG subclasses, DM20-IgG, and on rat brain tissue-based assay (TBA). Complement-dependent cytotoxicity (CDC) was assessed on a live CBA and antigen specificity and conformational binding through immunoadsorption/colocalization/fixation experiments. PLP1-IgG were found in 0 of 177 controls and 42 of 1104 patients with ADDs mainly diagnosed as other ADDs (19/42) with frequent myelitis/encephalomyelitis (14/19) and coexisting PNS involvement (13/19). Four of 19 patients with other ADDs fulfilled the seronegative NMOSD criteria. PLP1-IgG were also found in patients with MOGAD (11/42), more frequently with PNS involvement (p = 0.01), and in patients with MS (12/42), more frequently with atypical features (p < 0.001). PLP1-IgG-positive MOGAD had higher EDSS scores (p < 0.001) and PLP1-IgG-positive MS had higher severity scores (MSSS, p < 0.001) compared with those PLP1-IgG-negative. Overall, PLP1-IgG were found in 24.1% of patients with CNS+PNS-ADD, 21.2% with atypical MS, 8.3% with MOGAD, 12.0% with seronegative NMOSD, and 1.4% with typical MS. Their frequency within each diagnostic subgroup was consistent between the exploratory and validation cohorts. PLP1-IgG a) colocalized with their target on CBA-TBA, where their binding was abolished after immunoadsorption and fixation-induced conformational epitope alteration; b) mostly pertained to the IgG1/IgG3 subclass (68.3%) and were able to induce CDC; and c) coreacted with DM20 in all 12 patients with PNS involvement tested. Conformational PLP1-IgG predominantly identify patients with non-MS ADDs. They should be tested mainly in those with CNS + PNS ADD, coherently with DM20-IgG coreactivity. PLP1-IgG could also be investigated as disease modifiers and prognostic markers in MS and MOGAD. Preliminary evidence supports their pathogenic potential.