Craniosynostosis is a congenital condition characterized by premature fusion of one or more cranial sutures, leading to abnormal head shapes in children. Imaging plays a critical role in diagnosis, surgical planning, and monitoring, with various modalities available for use depending on clinical suspicion and syndromic involvement. The American Academy of Pediatrics recommends a tiered imaging approach based on clinical suspicion. Plain radiographs have limited value when craniosynostosis is strongly suspected; CT scans are reserved for confirmed or high-suspicion cases; and cranial ultrasound is a useful radiation-free screening tool but operator-dependent. The timing of surgical intervention depends on the suture involved and the surgical technique chosen, in discussion with the family. The timing of CT imaging should be discussed with the craniofacial team, as scans performed too early for diagnosis may require repeat imaging before surgery. Early referral to a craniofacial team is advised. Syndromic craniosynostosis often requires additional imaging and may present with brain anomalies like ventriculomegaly, callosal thinning, Chiari I malformations, and venous malformations.
Elevated intracranial pressure (ICP) is the physiologic link connecting the craniofacial diagnosis of craniosynostosis to the pediatric neurologist's core concerns—vision, development, and long-term neurologic outcome—yet it frequently evades clinical detection until harm has already occurred. This review synthesizes current evidence on the recognition, mechanisms, and management of elevated ICP in craniosynostosis to equip pediatric neurologists for this role. Elevated ICP risk tracks closely with the distinction between single suture nonsyndromic and multi-suture or syndromic disease, arising from multifactorial and often co-existing mechanisms—including craniocerebral disproportion, venous hypertension, hydrocephalus, Chiari I malformation, and obstructive sleep apnea—whose relative contributions differ by phenotype. No single noninvasive test reliably detects elevated ICP: fundoscopy, optical coherence tomography, visual evoked potentials, and neuroimaging each carry mechanism-specific blind spots, so detection depends on serial, multimodal surveillance rather than any one test. Cranial vault expansion remains first-line treatment, but postoperative recurrence is common, particularly in syndromic patients, in whom the dominant driver of ICP elevation may shift over time, necessitating structured, long-term follow-up integrating neurologic, ophthalmologic, developmental, and sleep assessment. Since elevated ICP in craniosynostosis is frequently silent and its risk evolves throughout childhood, pediatric neurologists are uniquely positioned, through longitudinal surveillance and multidisciplinary coordination, to detect it early and prevent irreversible neurodevelopmental harm.
New Onset Refractory Status Epilepticus (NORSE) and Febrile Infection-Related Epilepsy Syndrome (FIRES) present significant diagnostic challenges. To date, no single testing modality has emerged as the standard to confirm or exclude NORSE/FIRES. However, there has been increasing characterization of NORSE/FIRES by magnetic resonance imaging (MRI), electroencephalogram (EEG), and serum and cerebrospinal fluid (CSF) biomarkers. Here we briefly summarized the MRI abnormalities including “The claustrum sign”. Dynamic contrast-enhanced MRI, a novel MRI sequence, highlighted increased blood-brain barrier permeability in individuals with NORSE. Several EEG features such as prolonged focal fast activity at seizure onset, shifting seizures, and extreme delta brush may be early findings in children with FIRES. Serum cytokine profiles demonstrated distinct immunophenotypes in adults with cryptogenic NORSE and were separate from the control subjects. Conventional genetic study is unlikely to identify a genetic etiology; however, it remains an important diagnostic tool. Novel genetic analysis such as polygenic risk score demonstrated cryptogenic NORSE sharing similar genetic landscape with other autoimmune/autoinflammatory diseases, further supporting aberrant inflammation as a main pathological mechanism. Collectively, these modalities may be complementary; therefore, a multimodal approach should be considered for the diagnosis of NORSE/FIRES.
Background Febrile infection-related epilepsy syndrome (FIRES) and New-Onset Refractory Status Epilepticus (NORSE) are rare, devastating conditions characterized by sudden-onset seizures in previously healthy individuals. Management is hindered by a limited evidence base, a complex pathophysiology involving innate and adaptive immune dysregulation, and the “trial-and-error" nature of treating medication-resistant seizures within isolated clinical settings. Objective To bridge gaps in clinical experience and evidence, we established a recurring virtual international case-based conference that provides real-time multidisciplinary guidance for clinicians managing the acute and post-acute phases of FIRES and NORSE. Since inception in September of 2024, the monthly sessions have utilized a virtual platform to reach a global audience. Standardized 15–30-minute presentations highlighting clinical history, diagnostics, and immunomodulatory interventions were followed by moderated peer-to-peer dialogue. Outreach has been facilitated by the NORSE Institute, and the program achieved CME accreditation in January of 2026. Results Over an 18-month period, the initiative hosted 22 sessions discussing 40 cases (85% pediatric, 15% adult). Attendance stabilized at a median of 30-40 participants, peaking at 70, with consistent representation from 3 to 8 countries per session. Participants included epileptologists, neurointensivists, immunologists, rheumatologists, and researchers from both community hospitals and quaternary centers. Primary clinical inquiries focused on the duration and escalation of immunotherapy, diagnostic differentiation, and care transitions. Conclusions This international conference model represents a shift toward a collaborative, global expertise framework, effectively “democratizing” specialized knowledge for refractory status epilepticus, especially those possibly caused by rare neuroinflammatory diseases. While currently a descriptive, observational experience lacking patient-level outcome data, the initiative serves as a scalable template for developing a “community of learners.” Future efforts will focus on expanding outreach to adult providers and underrepresented geographic regions to further standardize the evidence-based care of FIRES and NORSE.
In this narrative review, we will summarize the existing literature describing long-term outcomes after new-onset refractory status epilepticus and febrile infection-related epilepsy syndrome. Febrile infection-related epilepsy syndrome is more common in children and has been described as a multiphasic presentation with a prodrome, an acute epileptic phase and a chronic epileptic phase. Important long-term sequelae after resolution of the acute phase of new-onset refractory status epilepticus and febrile infection-related epilepsy syndrome include survival and mortality, seizures, cognition and functioning, mental health and behavioral changes, general medical sequelae, quality of life and the enormous impact of these outcomes on caregivers and families.
New-onset refractory status epilepticus (NORSE) is a rare clinical condition characterized by the occurrence of refractory status epilepticus in previously healthy children or adults. When preceded by a febrile illness 1-14 days prior, it is known as Febrile Infection-Related Epilepsy Syndrome (FIRES). In most cases, no underlying etiology is identified despite extensive evaluation, and these patients are classified as having cryptogenic NORSE. The NORSE Institute was established to define the condition, increase awareness, and facilitate collaborative research, notably through the creation of a biorepository designed to collect biospecimens and clinical data from patients with NORSE. In recent years, extensive research has been conducted using these samples and datasets, as well as complementary resources from additional collaborating biorepositories. In this review, we summarize recent advances in the field, namely the development of guidelines for biospecimen collection and use, the characterization of immune dysfunction and its potential link to neuronal excitability and possibly to personalized treatments, the interaction between the microbiome and inflammatory pathways, and the characterization of clinical outcomes in patients with NORSE. Together, these advances are improving our understanding of NORSE mechanisms, helping to identify prognostic biomarkers and to support the development of personalized treatments.
New onset refractory status epilepticus (NORSE) and its subtype febrile infection-related epilepsy syndrome (FIRES) are severe presentations of epilepsy syndromes that are characterized by treatment refractory seizures in an individual without prior epilepsy. Some cases have identified etiologies, such as specific autoantibodies or viral infections, but many cases are classified as cryptogenic. There is increasing evidence suggesting that both adaptive and innate immune dysregulatory mechanisms play a central role in the pathogenesis of these disorders, particularly in cryptogenic cases, and with this, increased use of immunotherapy as a key component of treatment of NORSE and FIRES.
New-Onset Refractory Status Epilepticus (NORSE) and its sub-type, Febrile Infection-Related Epilepsy Syndrome (FIRES) is a profoundly challenging condition due to its rarity, diagnostic and prognostic uncertainty, and outcomes with high morbidity and mortality. While prior research has focused primarily on treatment strategies and outcomes in the acute phase, little attention has been given to how physician–family communication shapes clinical decision-making, long-term patient and family outcomes, and medical research. NORSE is characterized not only by its acuity but also by being an evolving and unpredictable condition. Parents have stated that they were not fully informed of their children’s dire medical conditions which often led to their feelings of mistrust of the medical team and poor discharge planning. If families turn away from established medicine because of poor communication and lack of trust in the medical team, the natural history of NORSE will remain unknown. Prognoses will continue to be nonspecific and unreliable if families do not communicate back to the medical establishment their experiences in the long term.The goal of Physician-Family communication is trust. Communication must be team-based, with the team made up of the physician leading the case, the family and the specialists involved so that all viewpoints can be heard. Communication must be frequent, and what is known and what remains uncertain be openly discussed. Parents require full, candid information to make the best, informed decisions for their children. As examples, five parents tell in their own words what they needed to know from their doctors to understand and plan for NORSE.
The treatment paradigm in new onset refractory status epilepticus (NORSE) and its subtype febrile infection-related epilepsy syndrome (FIRES) is generally multimodal, including treatments that target the underlying etiology (immunotherapy) and symptomatic treatment of seizures (anti-seizure medications (ASMs), ketogenic diet, and neuromodulation/epilepsy surgery). In the acute phase, treatment with escalating ASMs and anesthetic agents ensues as per other etiologies of refractory status epilepticus (RSE), with prompt initiation of ketogenic diet and first and second line, targeted immunotherapy. After resolution of RSE, treatment in the chronic phase consists of de-escalating ASM polypharmacy, acute immunotherapy, and often ketogenic diet while continuously considering side effect profile, seizure burden, and quality of life to find an appropriate balance. No single ASM is considered superior and treatment is tailored to the individual patient and side effect/comorbid disease profiles. Importantly, we lack high level evidence to guide symptomatic or targeted treatment in both the acute and post-acute phases, and further research is needed to identify the best treatment strategy.
New-onset refractory status epilepticus (NORSE) is a rare but severe neurological condition affecting both children and adults without prior epilepsy and without an identifiable acute cause at presentation. A substantial proportion of patients progress to super-refractory status epilepticus, which is associated with high morbidity and mortality. Despite its clinical severity, diagnostic strategies remain heterogeneous and are largely based on expert consensus due to limited high-quality evidence.This article summarizes current concepts in the definition, clinical recognition, and diagnostic evaluation of NORSE and its subtype febrile infection-related epilepsy syndrome (FIRES). Early identification is critical, as the clinical course, often characterized by a prodromal phase followed by rapidly escalating, treatment-refractory seizures, may provide important diagnostic clues. A structured diagnostic approach is essential and should include early, broad investigation for infectious, autoimmune, paraneoplastic, metabolic, and genetic etiologies, combined with continuous reassessment as new clinical information emerges.Key diagnostic tools include comprehensive blood and cerebrospinal fluid analyses, continuous EEG monitoring, and early neuroimaging, supplemented by advanced techniques such as cytokine panels, metagenomic sequencing and genetic testing when indicated. However, in more than half of cases, no etiology is identified, and patients are classified as having cryptogenic NORSE.Given the potential for treatable causes and the impact of early targeted therapy, timely and systematic evaluation is essential. We here provide an overview of current diagnostic strategies and propose a practical framework to support clinicians managing this complex condition.
Concussion, or mild traumatic brain injury, is a common functional brain injury with heterogeneous symptoms affecting physical, cognitive, emotional, visual, vestibular, and autonomic domains. Although most children and adolescents recover within several weeks, a substantial minority develop persistent symptoms that interfere with school participation, physical activity, and quality of life. This review summarizes principles of multidisciplinary assessment and rehabilitation for prolonged or complex concussion recovery, using the clinical model of the Multidisciplinary Concussion Clinic at Boston Children’s Hospital as a practical framework. Persistent post-concussion symptoms often reflect multiple interacting impairments rather than a single unresolved process. Multidisciplinary assessment helps identify vestibular, visual, pain related, cervical, cognitive, and exertional contributors to prolonged recovery, improving patient experience and allowing more efficient, less fragmented care. Key management strategies include graded sub-symptom aerobic exercise, vestibular and oculomotor rehabilitation, treatment of post-traumatic headache and cervical pain, vision-based interventions, and individualized return-to-learn planning. Persistent post-concussion symptoms are best approached as a complex clinical problem requiring active, symptom-targeted, multidisciplinary care that can streamline recommendations and treatment planning while supporting functional recovery.
Pediatric concussion frequently disrupts school participation, yet approaches to returning to the academic environment remain inconsistently implemented despite growing consensus on the benefits of early, supported school re-entry. This review synthesizes the extant literature on the evidence, clinical guidelines, educational policy, and multidisciplinary practice to examine return to school related issues for youth following concussion and to identify gaps between established recommendations and real-world applications. Across national and international guidelines, early return to school with symptom-limited cognitive activity is consistently endorsed, while prolonged cognitive rest and delayed academic re-entry are no longer supported. Additionally, students commonly experience learning, sensory, emotional, and environmental challenges that extend beyond school re-entry alone, especially in secondary settings with greater demand variability, highlighting limitations of narrowly framed “return-to-learn” (RTL) and “return-to-school” (RTS) models.Evidence indicates that concussion-related school difficulty reflects an interaction among personal factors such as symptom burden and cognitive endurance, with medical guidance, environmental demands, and institutional constraints, with older students potentially facing disproportionate challenges. Although multidisciplinary care models—including school-based teams, rehabilitation providers, and mental health and medical professionals—are widely recommended, operational guidance for role delineation, communication, and accommodation fidelity remains limited, oftentimes resulting in delays in implementation. As a result, practices related to returning students to the academic environment vary widely across schools and jurisdictions, contributing to inequitable access to effective supports. This review emphasizes the need to facilitate supported return to full school participation rather than solely academic reintegration and outlines practical strategies and research priorities to improve implementation and outcomes.
