Lorna Stemberger Marić

Background: Due to increasing proportion of asymptomatic severe acute respiratory syndrome coronavirus 2 infections and previously reported overlapping features, the distinction between Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) remains challenging. Statistical differentiation models for clinical guidance are scarce and should focus on cardiac involvement, as differences in cardiac involvement might serve as a potential clinical finding for early recognition of MIS-C. Methods: We retrospectively analyzed 298 MIS-C and KD cases treated during the 22-year period (from 2003 to 2024), and compared demographic, clinical, laboratory, ultrasound and cardiac findings. A multivariable differentiation model based on clinical, laboratory, ultrasound and cardiac features was developed for distinguishing KD/MIS-C cases. Results: Of 298 cases, 162 (54.4%) were diagnosed with KD. MIS-C patients were significantly older (109.1 vs. 45.5 months, P < 0.001) and had higher admission rates to the intensive care unit (52.2% vs. 29.0%, P < 0.001). Rash ( P < 0.001), conjunctivitis ( P = 0.013), mucosal ( P < 0.001) and extremity changes ( P < 0.001) were more common in KD, while gastrointestinal symptoms were more common in MIS-C ( P < 0.001). MIS-C patients also had higher C-reactive protein values ( P < 0.001). Pericarditis, congestive heart failure and mitral regurgitation ( P < 0.001) were more common in MIS-C patients. Based on our model, older age, higher C-reactive protein values, gastrointestinal symptoms, hyponatremia, presence of ascites and mitral regurgitation were predictive of MIS-C. Conclusions: Our model is the first to report mitral regurgitation as a potential diagnostic hallmark for MIS-C. Comprehensive clinical, laboratory and ultrasound evaluation of patients with overlapping features of KD/MIS-C improves diagnostic yield. Future models should increase sample size and focus on external model validation.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment by reactivating T cell-mediated anti-tumor immunity. However, this enhanced immune activity can lead to immune-related adverse events (irAEs). This narrative review focuses on endocrine irAEs, including thyroid dysfunction, hypophysitis, adrenal insufficiency, and diabetes mellitus. It also explores infectious complications and their underlying mechanisms. These mechanisms include immune dysregulation resulting directly from ICI-induced T-cell activation and indirectly from the immunosuppressive therapies used to treat irAEs. Furthermore, potential role of endocrine irAEs in predisposing patients to infectious complications is analyzed. The objective is to provide non-oncology specialists with the clinical insight necessary to recognize and manage these complex side effects. This narrative review synthesizes current literature on the diagnosis, management, and pathophysiology of endocrine irAEs and infections associated with different classes of ICIs (anti-CTLA-4, anti-PD-1, and anti-PD-L1). Endocrine irAEs are common, with incidence varying by ICI type; combination therapies pose the highest risk. Thyroid dysfunction is the most frequent, followed by hypophysitis, which often leads to permanent secondary adrenal insufficiency. ICI-induced diabetes mellitus is a rare but serious complication, frequently presenting as diabetic ketoacidosis. ICIs are believed to induce a distinct array of infections resulting from immunological dysregulation, unrelated to immunosuppressive medication. The phenomenon is increasingly called ICI therapy-induced dysregulated immunity. Moreover, evidence suggests that endocrine irAEs can compromise immune function and lead to a significantly higher risk of bacterial and fungal infections. Identifying infections that imitate irAEs is particularly important because the therapy is significantly distinct. Greater interdisciplinary awareness is crucial for the early recognition and appropriate management of both the endocrine and infectious complications, ultimately improving the safety and outcomes for patients receiving immunotherapy.

Background: Mycoplasma pneumoniae is a common cause of respiratory tract infections in children, but neurological complications, including encephalitis, are increasingly recognized. Basal ganglia involvement is rare, and a poorly characterized feature of meningoencephalitis, with clinical consequences being inconclusive. Methods: We report two pediatric cases of Mycoplasma pneumoniae-related meningoencephalitis with bilateral basal ganglia lesions seen on MRI. A literature review was conducted using PubMed, Scopus, and Web of Science to identify reports of M. pneumoniae-related meningoencephalitis in children, and related MRI findings. Results: Both patients (12-year-old male and 14-year-old female) presented with acute meningoencephalitis syndrome and had marked mononuclear pleocytosis. In both patients M. pneumoniae was confirmed with serological assay from serum sample, while in one patient M. pneumoniae was also confirmed by PCR from pharyngeal swab. Both exhibited bilateral basal ganglia lesions, with complete regression observed during follow-up. Treatment with corticosteroids led to full recovery in both cases. After a literature search, a total of 21 patients had basal ganglia involvement reported. Conclusions: Literature suggests variable MRI findings in pediatric M. pneumoniae encephalitis, with basal ganglia involvement being uncommon and rarely reported, especially among older children. While diagnostic challenges related to extrapulmonary manifestations of the infection persist, basal ganglia involvement could aid in diagnosis, especially in older children presenting with meningoencephalitis along with pronounced pleocytosis when respiratory symptoms are absent or mild.

Background Despite diagnostic advancements, high rates of unidentified acute encephalitis cases persist among pediatric patients, and novel causative agents are emerging. This study investigates features of pediatric acute encephalitis cases, evaluates the impact of diagnostic improvements and identifies risk factors for sequelae. Methods We analysed acute encephalitis cases (aged 0 to 18 years) from January 2006 to December 2023. We compared epidemiological, clinical, laboratory, electroencephalographic, and neuroimaging features between patients with known and unknown, as well as infective and non-infective etiology, and assessed factors associated with sequelae. Results Among 235 acute encephalitis cases (50.2% males, median age 96 months), etiology was identified in 62.1%, with acute disseminated encephalomyelitis being the most common (44.2%). Infectious agents were confirmed in 28.9% cases. Patients with known etiology had longer hospital stay (p = 0.041), higher rates of abnormal MRI findings (p = 0.001) and sequelae at discharge (p = 0.005). Younger age (aOR = 0.80, p = 0.015), abnormal MRI findings (aOR = 2.98, p = 0.009), non-infectious etiology (OR = 2.88, p = 0.006) and higher CSF protein levels (aOR = 5.39, p = 0.017) were associated with sequelae. Etiology detection rate did not differ significantly after the introduction of autoimmune encephalitis panel and meningitis-encephalitis panel (66.2% vs. 60.9% vs. 62.5%, p = 0.768). Conclusion Immune-mediated causes of acute encephalitis are increasing. Despite diagnostic improvements, the rates of successful etiology determination are still suboptimal. Neuroradiologic assessment should be prioritized, as it enhances the identification of the underlying cause and can serve as a prognostic factor in determining outcomes.

Background: Enteroviruses, members of the Picornaviridae family, typically cause asymptomatic or mild infections. However, they can also result in central nervous system (CNS) involvement, with transverse myelitis (TM) occurring only on rare occasions. TM is a syndrome characterized by acute or subacute spinal cord dysfunction, leading to neurological deficits below the level of the lesion. Case report: We report a case series of eight pediatric patients admitted over a three-month period, June to August 2024. All patients presented with ataxia and/or other neurological symptoms, alongside abnormal cerebrospinal fluid (CSF) findings. Although ataxia is commonly associated with cerebellitis, magnetic resonance imaging (MRI) in this cohort revealed findings consistent with TM. Notably, all patients demonstrated similar MRI abnormalities. The onset of symptoms occurred over a short time during an enterovirus epidemic. Enteroviral RNA was detected, or the virus was isolated in seven patients, while one patient had a close epidemiological link to the virus. All patients achieved full recovery following immunomodulatory therapy. Conclusions: This case series underscores that ataxia may be an atypical symptom associated with TM. Furthermore, there was a notable distinction between the clinical presentation and neuroradiological findings. Immunomodulatory therapy with immunoglobulins and corticosteroids has been shown to be effective and safe, supporting the hypothesis of an immune-mediated pathogenesis in these patients.

Congenital cytomegalovirus infection is the most common congenital infection worldwide and an important cause of neurodevelopmental delay and sensorineural hearing loss. Neuroimaging represents the best prognostic marker in cCMV infection. The aim of this study was to establish the role of cranial ultrasound and brain magnetic resonance imaging in the development of long-term sequelae in symptomatic and asymptomatic children with cCMV infection. Of the 47 children enrolled in the study, 25 (53.1%) were classified as symptomatic at birth. In 27/47 patients, SNHL was diagnosed with a similar proportion among the symptomatic and asymptomatic at birth (51.8% and 48.1%, respectively; p = 1.0). Thirty case patients had available data on follow-up. Neurological sequelae were more frequently seen in patients with symptomatic cCMV, but only cerebral abnormalities seen on initial MRI results had a consequential link with the later development of motor (OR 17.5; 95% Cl: 2667, 114,846; p = 0.002) and speech disorders (OR 15; 95% Cl: 2477, 90,843; p = 0.02). Although not statistically significant, hearing deterioration was more frequent in children with abnormal MRI results (OR 5; 95% Cl: 0.846, 29,567; p = 0.121). Neuroimaging abnormalities, as identified through both cranial ultrasound (CrUS) and MRI, are critical prognostic indicators for long-term sequelae, applicable to both symptomatic and asymptomatic children.

Background/Objectives: While the concept of viral community-acquired pneumonia (CAP) changed with COVID-19, the role of non-influenza viruses as a cause of CAP is less clear. The aim of this study was to describe the clinical course, risk factors, inflammatory profiles, antibiotic use, outcomes and complications of adenoviral (AdV) CAP. Methods: A prospective, non-interventional, observational cohort study included consecutively hospitalized immunocompetent adult patients with AdV CAP during an 18-month period. Clinical and laboratory data, including lymphocyte subpopulations and serum cytokine profiles were collected and correlated to clinical outcomes. Results: Fifty-eight patients with AdV CAP were included; 81% were males, with a median age of 33 (IQR 28–41) years and 62% without any comorbidities. All patients initially had high-grade fever for a median duration of 6 (5–7) days and respiratory symptoms. Increased CRP and procalcitonin, lymphopenia, mild thrombocytopenia and liver injury were frequent. Radiographic findings mimicked bacterial pneumonia (83% had unilateral involvement). Twenty-two patients (38%) had criteria for severe CAP, and these patients had higher procalcitonin, NLR, AST, ALT, LDH and CK, and lower T-lymphocyte CD4+ count. In comparison to influenza and bacterial CAP, patients with AdV had higher serum IL-2, IL-1β, IL-8, IL-10, CXCL10 and MCP-1, and lower TGF-β1 concentration. Thirteen patients required low-flow oxygen therapy, and 13 advanced respiratory support. Complications occurred in 29%, with one fatal outcome. While all patients received empirical antibiotic therapy, after AdV detection it was stopped in 21%, although only one patient had detected a possible bacterial coinfection. Conclusions: Since AdV CAP in immunocompetent patients is clinically and radiologically indistinguishable from bacterial CAP, it is associated with prolonged clinical course and lack of clinical response to antibiotics. This emphasizes the importance of AdV testing which could lead to more rational antimicrobial treatment.

Background: Papillary tumor of the pineal region (PTPR) represents a rare and histologically distinct subgroup of tumors originating in the pineal region. Few pediatric cases have been reported so far in the literature; therefore, clinical data are scarce. Case Description: We describe a case of PTPR in a 9-year-old girl who presented with a 5-month history of excessive appetite and weight gain. The patient underwent neuroimaging procedures and total gross surgical resection with postoperative adjuvant local radiotherapy, which from our experience was the best treatment choice as an attempt to avoid local recurrence. During 78-month follow-up, the patient from our study manifested no disease recurrence. Conclusion: PTPR should be included in the differential diagnosis of pineal region masses.