Search Results (43)

Background: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an uncommon inflammatory disorder of the central nervous system that is exceptionally rare during childhood. Although pontocerebellar punctate enhancement is considered its neuroradiological hallmark, the full spectrum of pediatric clinical and imaging manifestations remain poorly characterized because available evidence is limited to isolated case reports and small case series. We conducted a systematic review to characterize the clinical presentation, neuroimaging phenotype, diagnostic challenges, therapeutic strategies, and outcomes of pediatric CLIPPERS. Methods: A systematic literature search was conducted in PubMed/MEDLINE and Scopus from database inception to December 2025, following PRISMA guidelines. Studies reporting patients younger than 18 years with a diagnosis of CLIPPERS were eligible. Clinical, neuroradiological, laboratory, histopathological, therapeutic, and outcome data were extracted using a standardized form. Diagnostic certainty was assessed according to the Tobin criteria, and methodological quality was evaluated using the Joanna Briggs Institute (JBI) critical appraisal tools. Results: Ten studies comprising 13 pediatric patients fulfilled the inclusion criteria. Median age at presentation was 13 years (range 3–16 years), with a slight male predominance. Ataxia was the most common presenting manifestation (84.6%), followed by cranial nerve involvement (61.5%) and diplopia (46.2%). Magnetic Resonance Imaging (MRI) consistently demonstrated brainstem involvement, predominantly affecting the pons (84.6%) and cerebellum (76.9%), while supratentorial lesions (46.2%), midbrain involvement (46.2%), and spinal cord abnormalities (23.1%) suggest that the neuroradiological phenotype may extend beyond the classic pontocerebellar pattern, although these findings were observed in a limited number of patients. Cerebrospinal fluid (CSF) findings were nonspecific, typically showing normal results or mild lymphocytic pleocytosis. Histopathological examination, when available, demonstrated characteristic perivascular T-cell-predominant inflammatory infiltrates. All patients received high-dose corticosteroids with initial clinical improvement; however, relapses occurred in 61.5% of cases, frequently during corticosteroid tapering, often requiring steroid-sparing immunosuppressive therapy. Based on the available evidence, we suggest a practical clinic-radiological framework to facilitate the evaluation of children presenting with suspected CLIPPERS. Conclusions: Pediatric CLIPPERS represents a rare but increasingly recognized neuroinflammatory disorder characterized by marked corticosteroid responsiveness and a wide range of neuroradiological phenotypes. Although pontocerebellar involvement remains the defining imaging feature, supratentorial and spinal cord lesions are not uncommon and should not exclude the diagnosis after careful consideration of alternative inflammatory, autoimmune, infectious, and neoplastic disorders. Given the high relapse rate and the limited quality of available evidence, prolonged follow-up and collaborative multicenter studies are needed to refine pediatric diagnostic criteria and optimize long-term management. Full article

Detecting localized morphological anomalies in three-dimensional point clouds is difficult because geometric deviations are entangled with rigid pose variation, residual registration error, sampling noise, and normal inter-subject variability. This challenge is particularly relevant in translational neuroimaging, where abnormal shape changes may be subtle and abnormal annotations are scarce. We propose an unsupervised framework that formulates 3D anomaly detection as a two-stage factorization problem, termed AdvFlow3D-AD. First, Fast Global Registration, followed by multi-scale Iterative Closest Point refinement, establishes a common geometric reference frame and reduces rigid-body nuisance variation. Second, an adversarially regularized normalizing flow models the residual distribution of aligned normal coordinates, enabling localized anomaly scores based on distance from the learned normal latent support. Percentile calibration on normal data then defines interpretable point-level and object-level operating points without requiring abnormal samples during training. We evaluate AdvFlow3D-AD on the Real3D-AD and Anomaly ShapeNet3D datasets, achieving a point-level area under the receiver operating characteristic curve (AUROC) of 0.747 on Real3D-AD and an object-level AUROC of 0.816 on Anomaly ShapeNet3D. We further present an exploratory neurodevelopmental brain-shape case study involving pediatric perinatal-asphyxia cases. The resulting anomaly maps showed qualitative spatial correspondence with anatomically plausible hippocampal and cerebellar regions under neuroradiological review. These results suggest that separating geometric nuisance variation from residual morphology can support interpretable anomaly localization when abnormal labels are limited. Full article

Background: Heterozygosity for pathogenic variants in the ABCC6 gene has been associated with an increased incidence of cerebrovascular diseases. This study aims to characterize the prevalence and clinical and neuroradiological phenotypes associated with monoallelic and biallelic ABCC6 variants in pediatric and adult patients presenting with arterial ischemic stroke or cerebral small vessel disease (CSVD). Methods: We conducted a retrospective observational study on 143 consecutive patients (48 pediatric, 24 juvenile, 71 adult) diagnosed with ischemic stroke or CSVD of unknown etiology. Clinical and neuroradiological data were collected and analyzed in relation to the identified genetic variants through next-generation sequencing. Results: Among the patients, 16 (11.2%) tested positive for causative variants in the ABCC6 gene, with 11 subjects carrying monoallelic variants and 5 carrying biallelic variants. Patients with biallelic variants exhibited severe and complex vasculopathy, with a high incidence of early ischemic events. In contrast, monoallelic carriers predominantly presented with microvascular disease manifestations, including lacunar strokes and signs of CSVD. Conclusions: The results suggest a significant age-dependent phenotypic divergence in patients with ABCC6 variants, highlighting the impact of heterozygosity on cerebrovascular health. Identifying these variants may enhance risk stratification and inform management strategies in patients with traditional vascular risk factors. Full article

Background: The GRIA3 gene encodes the GluA3 subunit of AMPA-type glutamate receptors, which are crucial for excitatory neurotransmission in the central nervous system. Pathogenic GRIA3 variants cause X-linked neurodevelopmental disorders of varying severity, including developmental delay, behavioral abnormalities, and epilepsy. Case Summary: Here, we present the case of a seven-year-old female patient presenting with developmental delay, spastic gait, and non-convulsive status epilepticus (NCSE), who was found to carry a novel de novo GRIA3 missense variant (c.1969A > G; p.Thr657Ala). The EEG revealed high-amplitude diffuse rhythmic theta/delta activity consistent with NCSE. A brain MRI showed transient cortical and thalamic T2-FLAIR hyperintensities, likely postictal. Metabolic investigations were unremarkable. Following intensive treatment with levetiracetam and midazolam, the patient gradually recovered to her baseline neurological status. Genetic Finding: Whole-exome sequencing (WES) identified a novel de novo variant in GRIA3, c.1969A > G; p.Thr657Ala, involving the replacement of threonine with alanine at position 657 within the coding region. Significance: This case expands the clinical and molecular spectrum of GRIA3-related disorders, demonstrating that females with de novo variants may experience severe epilepsy. This is the first reported case of NCSE in a female patient with a GRIA3 variant. Full article

Background: Acute otomastoiditis (AOM) may occasionally progress to severe intracranial complications in children. While immunological and microbiological factors have been studied, the role of temporal bone anatomical variants remains less well-defined. The aim of this study is to investigate the prevalence of anatomical variants in pediatric patients with acute complicated otomastoiditis (ACOM) compared to those with uncomplicated ones (AUOM) and healthy controls (HC) and assess their potential association with intracranial complication patterns. Methods: This retrospective, single-center study reviewed clinical and neuroradiological data of patients aged 0–16 years admitted for AOM between 2018 and 2025. ACOM patients were compared to AUOM and HC groups (the latter undergoing neuroimaging for minor head trauma). Two experienced neuroradiologists evaluated imaging to identify anatomical variants involving the following: (1) sigmoid sinus and emissary veins; (2) tegmen tympani; and (3) mastoid pneumatization. Statistical analyses assessed prevalence differences across groups. Results: Among 282 AOM patients, 58 had intracranial complications. Anatomical variants were significantly more frequent in ACOM patients versus both AUOM and HC (p < 0.01). In this subgroup, vascular anatomical variants were notably associated with vascular or combined (vascular and infectious) complications; tegmen tympani and mastoid pneumatization variants showed no significant subgroup associations. Conclusion: Anatomical variants, particularly vascular anomalies of the sigmoid sinus and emissary veins, appear to increase pediatric AOM patients’ susceptibility to intracranial complications. Recognition of these configurations through early neuroimaging could aid risk stratification and improve diagnostic and therapeutic strategies. Full article

Artificial intelligence (AI) is revolutionarily shaping the entire landscape of medicine and particularly the privileged field of radiology, since it produces a significant amount of data, namely, images. Currently, AI implementation in radiology is continuously increasing, from automating image analysis to enhancing workflow management, and specifically, pediatric neuroradiology is emerging as an expanding frontier. Pediatric neuroradiology presents unique opportunities and challenges since neonates’ and small children’s brains are continuously developing, with age-specific changes in terms of anatomy, physiology, and disease presentation. By enhancing diagnostic accuracy, reducing reporting times, and enabling earlier intervention, AI has the potential to significantly impact clinical practice and patients’ quality of life and outcomes. For instance, AI reduces MRI and CT scanner time by employing advanced deep learning (DL) algorithms to accelerate image acquisition through compressed sensing and undersampling, and to enhance image reconstruction by denoising and super-resolving low-quality datasets, thereby producing diagnostic-quality images with significantly fewer data points and in a shorter timeframe. Furthermore, as healthcare systems become increasingly burdened by rising demands and limited radiology workforce capacity, AI offers a practical solution to support clinical decision-making, particularly in institutions where pediatric neuroradiology is limited. For example, the MELD (Multicenter Epilepsy Lesion Detection) algorithm is specifically designed to help radiologists find focal cortical dysplasias (FCDs), which are a common cause of drug-resistant epilepsy. It works by analyzing a patient’s MRI scan and comparing a wide range of features—such as cortical thickness and folding patterns—to a large database of scans from both healthy individuals and epilepsy patients. By identifying subtle deviations from normal brain anatomy, the MELD graph algorithm can highlight potential lesions that are often missed by the human eye, which is a critical step in identifying patients who could benefit from life-changing epilepsy surgery. On the other hand, the integration of AI into pediatric neuroradiology faces technical and ethical challenges, such as data scarcity and ethical and legal restrictions on pediatric data sharing, that complicate the development of robust and generalizable AI models. Moreover, many radiologists remain sceptical of AI’s interpretability and reliability, and there are also important medico-legal questions around responsibility and liability when AI systems are involved in clinical decision-making. Future promising perspectives to overcome these concerns are represented by federated learning and collaborative research and AI development, which require technological innovation and multidisciplinary collaboration between neuroradiologists, data scientists, ethicists, and pediatricians. The paper aims to address: (1) current applications of AI in pediatric neuroradiology; (2) current challenges and ethical considerations related to AI implementation in pediatric neuroradiology; and (3) future opportunities in the clinical and educational pediatric neuroradiology field. AI in pediatric neuroradiology is not meant to replace neuroradiologists, but to amplify human intellect and extend our capacity to diagnose, prognosticate, and treat with unprecedented precision and speed. Full article

Mucormycosis is a rare invasive fungal disease in pediatric patients with hematological malignancies and is associated with poor outcomes. We present a fulminant and ultimately fatal case of rhino-orbito-cerebral mucormycosis, addressing important issues including clinical signs and symptoms, diagnostic approaches and the challenges of timely diagnosis. The patient was an 11-year old girl undergoing re-induction chemotherapy for Central Nervous System relapse of B-cell precursor acute lymphoblastic leukemia. She presented six days into the second course of chemotherapy in profound neutropenia with aggravating headaches, painful abducens nerve palsy and anisocoria. At first (day −3), no significant radiological or ophthalmological correlations were found, and methyl–prednisolone was started due to suspected vasculitis following ICU admission. After further clinical deterioration, a second MRI scan (day 0) revealed a prolonged occlusion of the left carotid artery, which was successfully stented in a neuroradiological intervention (day +1). However, during the next day the child developed clinical signs indicating severe cerebral dysfunction. An emergency CT scan showed complete infarction of the left hemisphere including a progredient perfusion deficit and beginning brain edema. Based on the unfavorable prognosis, best supportive care was initiated, and the patient deceased on day +2. Pathological and microbiological workup identified thrombotic infarction in all major cerebral arteries. While microscopy was suspicious for mucormycosis, nested PCR from retained blood specimens confirmed the genus Lichtheimia. Final NGS on brain tissue led to the identification of Lichtheimia ramosa. This case illustrates the rapidity and severity of Mucorales infection. It shows the importance of early clinical suspicion and the need for an aggressive laboratory testing algorithms. The stratification of risk factors and definition of red flags may be a future task fighting these infections. Full article

Recurrent facial palsy is a rare event in the pediatric population, mostly idiopathic or associated with common comorbidities or, rarely, observed in syndromic conditions. However, some cases are difficult to explain and need more accurate diagnostic approaches. In this work, we describe a pediatric case of recurrent facial palsy secondary to hyperostosis of the skull and narrowing of the neural foramina related to a SOST-related sclerosing bone dysplasia. To our knowledge, this is the first Italian case that is also related to a novel loss-of-function variant in the SOST gene. We highlight the clinical relevance of a proper early diagnosis and the need for correct monitoring of the clinical evolution, considering the natural history of the disease, to prevent/reduce severe neurological complications. Full article

Background: Mucopolysaccharidoses (MPSs) are rare lysosomal storage disorders characterized by multisystem involvement; notably, skeletal abnormalities known as dysostosis multiplex and varying degrees of central nervous system impairment. Accurate radiological evaluation is crucial for accurate diagnosis and effective planning. This study aims to describe the clinical and radiological features of patients with MPS managed at our tertiary care center. Methods: We retrospectively reviewed clinical and radiological data from eight patients with confirmed MPS treated at S. Orsola University Hospital (Bologna, Italy) since 2000. Imaging included conventional radiography, supplemented by MRI and CT. The findings were analyzed by MPS subtype and correlated with clinical evolution and therapeutic interventions. A literature review complemented the analysis. Results: The cohort included one patient with MPS I, two with MPS II, one with MPS III, and four with MPS IV. Common skeletal findings were vertebral deformities, hip dysplasia, and shortening of long bones. Patients with MPS IV showed the most severe bone involvement, including pronounced platyspondyly and odontoid hypoplasia. Follow-up imaging demonstrated progression of bone and CNS pathology despite enzyme replacement therapy (ERT). Conclusions: Our findings underscore the pivotal role of imaging in MPS management. Tailored radiological protocols and multidisciplinary care are crucial for optimizing diagnosis and monitoring disease progression. Full article

Background/Objectives: Pediatric acquired demyelinating syndromes (ADSs) encompass a heterogeneous group of disorders, including multiple sclerosis (MS), MOG antibody-associated disease (MOGAD), and neuromyelitis optica spectrum disorder (NMOSD), with distinct clinical trajectories and prognoses. While analyzed collectively at baseline to reflect real-world diagnostic uncertainty, outcome predictors were also examined according to final diagnosis. Identifying early predictors is crucial for optimizing long-term outcomes. Methods: We retrospectively analyzed 30 pediatric patients (mean onset age: 11.3 years) with ADSs. Clinical, radiological, CSF, antibody, and neurophysiological data were collected and analyzed alongside treatment strategies. Outcomes—EDSS scores, neuroradiological changes, and clinical status—were evaluated over a 3-year period. Results: Final diagnoses included MOGAD (36.6%), MS (33.3%), NMOSD (6.6%), ADEM (10%), and other ADSs (13.3%). At onset, ≥3 brain lesions were present in 76.7% of patients. Disease-modifying therapies (DMTs) were used in 37% and acute immunotherapy in 90%. EDSS progression was significantly associated with DMT use at multiple timepoints, with additional predictors including MRI lesion type, CSF findings, antibody status, and evoked potentials. At 3 years, neurocognitive function predicted clinical outcome. Conclusions: Early immunotherapy and baseline instrumental findings are key predictors of outcome in pediatric ADSs. MOGAD showed a more favorable course, while MS and NMOSD were associated with greater long-term disability. A comprehensive, early diagnostic approach is essential for improving prognosis. Full article

Background: Pediatric-onset multiple sclerosis (POMS) is a rare but often more aggressive form of multiple sclerosis, associated with early cognitive impairment and significant impact on quality of life. Multiple sclerosis and primary headaches, particularly migraine, are well established in adults, but data on pediatric populations remain limited. Methods: The purpose of this retrospective study was to examine 64 POMS patients, divided into groups with and without headaches, to determine potential correlations between headache presence, age at POMS onset, and MRI lesion burden. Results: Headaches were reported by 78% of patients, predominantly migraines (68%), with a significantly higher prevalence in females (74%). No significant differences were found in age at MS onset or lesion load on brain MRI between patients with and without headaches. Among those with headaches, migraines represented a higher frequency of attacks and a greater need for prophylactic treatment compared to other headache types. Headache characteristics, including pain location and associated symptoms, showed no correlation with age at MS onset or lesion burden. Conclusions: These findings indicate that while headaches are common in POMS and more frequent in females, their presence and features do not appear to directly influence the clinical or neuroradiological course of the disease. Further research with larger cohorts and longitudinal follow-up is warranted to better understand the underlying mechanisms and long-term impact of headaches in pediatric MS. Full article

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. Full article

Background/Objectives: Sleep disorders (SDs) and Restless Legs Syndrome (RLS) have been reported with high prevalence in Multiple Sclerosis (MS), but data on Pediatric-Onset MS (POMS) are scarce. This study aims to assess the prevalence of SDs, particularly RLS, in a POMS cohort and examine associated clinical features. Methods: We recruited POMS patients who attended the POMS Center of the Bambino Gesù Children’s Hospital between September 2021 and February 2023; they were evaluated for SDs using the Pittsburgh Sleep Quality Index (PSQI) or the Sleep Disturbance Scale for Children (SDSC) and screened for RLS. Correlations with demographical, clinical, neuroradiological, and laboratory findings were analyzed. Results: We recruited 44 POMS patients, of whom 39% were classified as “good sleepers” and 61% were identified as “poor sleepers.” RLS was diagnosed in 10 patients (22.7%). Those with RLS were older and had higher Expanded Disability Status Scale (EDSS) scores compared to non-RLS patients (p = 0.028; p = 0.03). The presence of RLS did not show any significant correlation with MRI lesion load or laboratory data. Conclusions: Our findings suggest an increased rate of SDs and RLS in pediatric MS patients compared to the general pediatric population. Clinical data could support a secondary form of RLS in this population, but results need further confirmation. Full article

Background/Objectives: This study aimed to evaluate the results of continuous intracranial pressure (ICP) monitoring in children with macrocephaly or rapidly increasing head circumference (HC) diagnosed as benign external hydrocephalus (BEH). Here, we report the absolute ICP measurements, ICP pulsatility, and slow ICP waves after at least 48 h of continuous monitoring in a cohort of 36 children diagnosed with BEH. Methods: A prospective study of continuous ICP monitoring was performed in 36 consecutive children with macrocephaly (HC above the 97.5th percentile) or rapidly increasing HC (at least crossing two percentile curves), diagnosed with BEH (22 boys and 14 girls with a mean age of 23.6 ± 13.3 months, minimum: 6, maximum 65), using an epidural sensor. For the first four children in the study, hard copies of the ICP values were obtained using an analog recorder. Starting from the fifth patient, the ICP signal was sampled at 200 Hz and stored on a computer using a computer-based data acquisition and analysis system (LabChart v8.1 software). Results: Clinical signs or symptoms were identified in 20 patients (55.6%). Delayed motor or language development was noted in 18 (50%) and 20 (55.6%) patients, respectively. In 13 patients, the enlargement of the subarachnoid spaces was found to be associated with an additional condition. The median of mean ICP values for the entire cohort was 17 mmHg, with a minimum of 6.7 mmHg and a maximum of 29 mmHg. All patients exhibited a percentage of B waves exceeding 20% during the night, with a median value of 47.4% (min: 23.2, max: 75). Three children had nocturnal plateau waves. At night, regular ICP recordings alternated with periods of significant increases in ICP, often exceeding 10 mmHg above baseline values. High-amplitude B waves were noted during these episodes, and the amplitude of the cardiac waveform at the peak of the B waves was consistently greater than 5 mmHg, displaying an abnormal morphology (P2 > P1). A ventriculoperitoneal shunt was implanted in 30 of the 36 patients. Conclusions: Patients with BEH may present significant abnormalities in ICP. Monitoring this variable in certain cases can assist in determining the necessity for surgical treatment. Full article

Background and purpose: Perforator stroke (PS) is a subtype of perinatal arterial ischemic stroke (PAIS), in which injuries occur in the territory of the perforator branches of the main cerebral arteries. This study aims to explore the incidence, timing, risk factors, and clinical presentation of PS in both preterm and full-term neonates. Material and methods: We retrospectively analyzed data about all the neonatal brain MRIs carried out in our hospital from March 2012 to March 2023. Criterium of inclusion was the radiologically confirmed diagnosis of perforator stroke involving one or more arterial districts. Results: A total of 1928 patients underwent brain MRIs during the period considered. PAIS was present in 50 patients, of which 19 had PS (38%). Among the patients with PS, nine were preterm babies (47%), and six suffered from perinatal asphyxia (31.5%). PS cUS diagnosis preceded MRI diagnosis in 88% of preterm babies. The mean age at cUS diagnosis was 20 ± 7 days. Preterm babies were often asymptomatic, whereas term babies showed neurological symptoms (mainly seizures). The outcome was favorable as long as PS was isolated. Conclusions: PS is surprisingly frequent among PAIS. It represents the most common form of PAIS in preterm babies and in babies suffering from birth asphyxia. Prenatal and perinatal factors suggesting a possible thromboembolic etiology leading to PAIS are rare in our population of preterm babies, in which the diagnosis was always preceded by negative cUS. These assumptions suggest a postnatal development of PS in premature babies more than a perinatal one. Full article