Widespread, depth-dependent cortical microstructure alterations in pediatric focal epilepsy.

OBJECTIVE: Tissue abnormalities in focal epilepsy may extend beyond the presumed focus. The underlying pathophysiology of these broader changes is unclear, and it is not known whether they result from ongoing disease processes or treatment-related side effects, or whether they emerge earlier. Few studies have focused on the period of onset for most focal epilepsies, childhood. Fewer still have utilized quantitative magnetic resonance imaging (MRI), which may provide a more sensitive and interpretable measure of tissue microstructural change. Here, we aimed to determine common spatial modes of changes in cortical architecture in children with heterogeneous drug-resistant focal epilepsy and, secondarily, whether changes were related to disease severity. METHODS: To assess cortical microstructure, quantitative T1 and T2 relaxometry (qT1 and qT2) was measured in 43 children with drug-resistant focal epilepsy (age range = 4-18 years) and 46 typically developing children (age range = 2-18 years). We assessed depth-dependent qT1 and qT2 values across the neocortex, as well as their gradient of change across cortical depths. We also determined whether global changes seen in group analyses were driven by focal pathologies in individual patients. Finally, as a proof-of-concept, we trained a classifier using qT1 and qT2 gradient maps from patients with radiologically defined abnormalities (MRI positive) and healthy controls, and tested whether this could classify patients without reported radiological abnormalities (MRI negative). RESULTS: We uncovered depth-dependent qT1 and qT2 increases in widespread cortical areas in patients, likely representing microstructural alterations in myelin or gliosis. Changes did not correlate with disease severity measures, suggesting they may represent antecedent neurobiological alterations. Using a classifier trained with MRI-positive patients and controls, sensitivity was 71.4% at 89.4% specificity on held-out MRI-negative patients. SIGNIFICANCE: These findings suggest the presence of a potential imaging endophenotype of focal epilepsy, detectable irrespective of radiologically identified abnormalities.

Recommendations for neuroradiological examinations in children living with achondroplasia: a European Society of Pediatric Radiology and European Society of Neuroradiology opinion paper.

Children living with achondroplasia are at an increased risk of developing neurological complications, which may be associated with acute and life-altering events. To remediate this risk, the timely acquisition of effective neuroimaging that can help to guide clinical management is essential. We propose imaging protocols and follow-up strategies for evaluating the neuroanatomy of these children and to effectively identify potential neurological complications, including compression at the cervicomedullary junction secondary to foramen magnum stenosis, spinal deformity and spinal canal stenosis. When compiling these recommendations, emphasis has been placed on reducing scan times and avoiding unnecessary radiation exposure. Standardized imaging protocols are important to ensure that clinically useful neuroimaging is performed in children living with achondroplasia and to ensure reproducibility in future clinical trials. The members of the European Society of Pediatric Radiology (ESPR) Neuroradiology Taskforce and European Society of Neuroradiology pediatric subcommittee, together with clinicians and surgeons with specific expertise in achondroplasia, wrote this opinion paper. The research committee of the ESPR also endorsed the final draft. The rationale for these recommendations is based on currently available literature, supplemented by best practice opinion from radiologists and clinicians with subject-specific expertise.

Obstructive hydrocephalus due to an enlarged massa intermedia treated with endoscopic third ventriculostomy.

The massa intermedia (MI) or interthalamic adhesion (ITA) is a band of tissue connecting the medial surfaces of the thalami and is present in the majority of healthy individuals. Its enlargement as well as its absence have been associated with some pathological states.We describe the first case report of a 3-year-old child presenting with obstructive hydrocephalus in the context of an enlarged massa intermedia. The patient's symptoms abated following an endoscopic third ventriculostomy.

Metabolic patterns in brain 18F-fluorodeoxyglucose PET relate to aetiology in paediatric dystonia.

There is a lack of imaging markers revealing the functional characteristics of different brain regions in paediatric dystonia. In this observational study, we assessed the utility of [18F]2-fluoro-2-deoxy-D-glucose (FDG)-PET in understanding dystonia pathophysiology by revealing specific resting awake brain glucose metabolism patterns in different childhood dystonia subgroups. PET scans from 267 children with dystonia being evaluated for possible deep brain stimulation surgery between September 2007 and February 2018 at Evelina London Children's Hospital (ELCH), UK, were examined. Scans without gross anatomical abnormality (e.g. large cysts, significant ventriculomegaly; n = 240) were analysed with Statistical Parametric Mapping (SPM12). Glucose metabolism patterns were examined in the 144/240 (60%) cases with the 10 commonest childhood-onset dystonias, focusing on nine anatomical regions. A group of 39 adult controls was used for comparisons. The genetic dystonias were associated with the following genes: TOR1A, THAP1, SGCE, KMT2B, HPRT1 (Lesch Nyhan disease), PANK2 and GCDH (Glutaric Aciduria type 1). The acquired cerebral palsy (CP) cases were divided into those related to prematurity (CP-Preterm), neonatal jaundice/kernicterus (CP-Kernicterus) and hypoxic-ischaemic encephalopathy (CP-Term). Each dystonia subgroup had distinct patterns of altered FDG-PET uptake. Focal glucose hypometabolism of the pallidi, putamina or both, was the commonest finding, except in PANK2, where basal ganglia metabolism appeared normal. HPRT1 uniquely showed glucose hypometabolism across all nine cerebral regions. Temporal lobe glucose hypometabolism was found in KMT2B, HPRT1 and CP-Kernicterus. Frontal lobe hypometabolism was found in SGCE, HPRT1 and PANK2. Thalamic and brainstem hypometabolism were seen only in HPRT1, CP-Preterm and CP-term dystonia cases. The combination of frontal and parietal lobe hypermetabolism was uniquely found in CP-term cases. PANK2 cases showed a distinct combination of parietal hypermetabolism with cerebellar hypometabolism but intact putaminal-pallidal glucose metabolism. HPRT1, PANK2, CP-kernicterus and CP-preterm cases had cerebellar and insula glucose hypometabolism as well as parietal glucose hypermetabolism. The study findings offer insights into the pathophysiology of dystonia and support the network theory for dystonia pathogenesis. 'Signature' patterns for each dystonia subgroup could be a useful biomarker to guide differential diagnosis and inform personalized management strategies.

Radiologic diagnosis of non-traumatic paediatric head and neck emergencies.

Imaging plays a crucial role in evaluating paediatric patients with non-traumatic head and neck lesions in an emergency setting because clinical manifestations of these entities can overlap. For this reason, radiologists must be familiar with the clinical and imaging findings of prevalent paediatric head and neck emergencies. In this review, we present techniques and imaging clues for common complications of pathological processes in the paediatric head and neck, with a focus on the clinical scenario as a starting point for the radiologic approach.

Clinical Reasoning: A Teenage Girl With Progressive Hyperkinetic Movements, Seizures, and Encephalopathy.

The "epilepsy-dyskinesia" spectrum is increasingly recognized in neurogenetic and neurometabolic conditions. It can be challenging to diagnose because of clinical and genetic heterogeneity, atypical or nonspecific presentations, and the rarity of each diagnostic entity. This is further complicated by the lack of sensitive or specific biomarkers for most nonenzymatic neurometabolic conditions. Nevertheless, clinical awareness and timely diagnosis are paramount to facilitate appropriate prognostication, counseling, and management.This report describes a case of a teenage girl who had presented at 14 months with a protracted illness manifesting as gastrointestinal upset and associated motor and cognitive regression. A choreoathetoid movement disorder, truncal ataxia, and microcephaly evolved after the acute phase. Neurometabolic and inflammatory investigations, EEG, brain MRI, muscle biopsy (including respiratory chain enzyme studies), and targeted genetic testing were unremarkable. A second distinct regression phase ensued at 14 years consisting of encephalopathy, multifocal motor seizures, absent deep tendon reflexes and worsening movements, gut dysmotility, and dysphagia. Video EEGs showed an evolving developmental and epileptic encephalopathy with multifocal seizures and nonepileptic movements. MRI of the brain revealed evolving and fluctuating patchy bihemispheric cortical changes, cerebellar atrophy with signal change, mild generalized brain volume loss, and abnormal lactate on MR spectroscopy. The article discusses the differential diagnostic approach and management options for patients presenting with neurologic regression, encephalopathy, seizures, and hyperkinetic movements. It also emphasizes the utility of next-generation sequencing in providing a rapid, efficient, cost-effective way of determining the underlying etiology of complex neurologic presentations.

Guidelines for magnetic resonance imaging in pediatric head and neck pathologies: a multicentre international consensus paper.

The use of standardized imaging protocols is paramount in order to facilitate comparable, reproducible images and, consequently, to optimize patient care. Standardized MR protocols are lacking when studying head and neck pathologies in the pediatric population. We propose an international, multicenter consensus paper focused on providing the best combination of acquisition time/technical requirements and image quality. Distinct protocols for different regions of the head and neck and, in some cases, for specific pathologies or clinical indications are recommended. This white paper is endorsed by several international scientific societies and it is the result of discussion, in consensus, among experts in pediatric head and neck imaging.

Coronavirus Disease 2019 (COVID-19)-Associated Rhino-Orbito-Cerebral Mucormycosis: A Multi-Institutional Retrospective Study of Imaging Patterns.

BACKGROUND: Mucormycosis infection of the maxillofacial region and brain has been associated with coronavirus disease 2019 (COVID-19) infection. Mucormycosis was relatively a rare infection before COVID-19, and imaging findings are not very well described. MATERIALS AND METHODS: A retrospective imaging study of 101 patients diagnosed with COVID-19-associated mucormycosis by histopathology and/or culture was performed. All patients underwent computed tomography and/or magnetic resonance imaging based on the clinical condition of the patient and on consensus decision by the team of treating physicians. A simple 3-stage classification system based on imaging findings was adopted. RESULTS: One hundred one cases were included in the final analysis (mean age = 55.1 years; male/female ratio = 67:34). The affected patients had diabetes in 94% of the instances (n = 95), 80.1% (n = 81) received steroids), whereas 59.4% (n = 60) patients received supplemental oxygen. The majority underwent surgical intervention, whereas in 6 cases, patients were treated with antibiotic regimens. Sixty subjects improved following therapy, whereas 18 eventually succumbed to the illness. We noted a significant positive correlation between the imaging stage and outcomes. No association was seen between other clinical parameters and final clinical outcomes. Salient imaging findings include lack of normal sinonasal mucosal enhancement, perisinus inflammation, ischemic optic neuropathy, perineural spread, pachymeningeal enhancement, and presence of strokes. CONCLUSIONS: We describe the imaging findings in the largest cohort of patients with rhino-orbito-cerebral mucormycosis in the context of the current COVID-19 pandemic. A simplified staging system described here is helpful for standardized reporting and carries prognostic information.

Clinical features, investigations, and outcomes of pediatric limbic encephalitis: A multicenter study.

OBJECTIVES: To describe the clinical presentation, investigations, management, and disease course in pediatric autoimmune limbic encephalitis (LE). METHODS: In this retrospective observational study, from the UK Childhood Neuroinflammatory Disease network, we identified children from six tertiary centers with LE <18 years old between 2008 and 2021. Clinical and paraclinical data were retrieved from medical records. RESULTS: Twenty-five children fulfilling LE criteria were identified, with median age of 11 years (IQR 8, 14) and median follow-up of 24 months (IQR 18, 48). All children presented with seizures; 15/25 (60%) were admitted to intensive care. Neuroimaging demonstrated asymmetric mesial temporal changes in 8/25 (32%), and extra-limbic changes with claustrum involvement in 9/25 (38%). None were positive for LGI1/CASPR2 antibodies (Abs), 2/25 were positive for serum anti-NMDAR Abs, and 2/15 positive for anti-Hu Abs; one died from relapsing neuroblastoma. Two children had serum and CSF anti-GAD antibodies. Initial immune therapy included steroids in 23/25 (92%), intravenous immunoglobulin (IVIg) in 14/25 (56%), and plasma exchange in 7/25 (28%). The commonest second-line treatment was rituximab in 15/25 (60%). Median duration of hospital admission was 21 days (IQR 11, 30). At last follow-up, 13/25 (52%) had refractory seizures and 16/25 (64%) had memory impairment. Six children (24%) had modified Rankin Scale (mRS) scores ≥3. There was no significant difference in mRS, or long-term cognitive and epilepsy outcomes in those who received rituximab versus those who did not. INTERPRETATION: A diagnosis of autoimmune LE was associated with significant morbidity and adverse outcomes in this pediatric cohort.

Acute Myelopathy in Childhood.

Acute myelopathy presenting in childhood can be clinically classified based on the location of injury (with resulting spinal syndrome) or the cause (broadly traumatic or non-traumatic). Types of nontraumatic myelopathy include ischaemic, infectious, inflammatory, nutritional, and metabolic causes, some of which may be part of a systemic illness such as systemic lupus erythematosus or a demyelinating disease such as multiple sclerosis. Nonaccidental injury is an important consideration in cases of traumatic myelopathy, which may often be associated with other injuries. Assessment should include neuroimaging of the brain and spinal cord, with further investigations targeted based on the most likely differential diagnoses; for example, a child with suspected demyelinating disease may require specialist cerebrospinal fluid and serological testing. Management also will differ based on the cause of the myelopathy, with several of these treatments more efficacious with earlier initiation, necessitating prompt recognition, diagnosis, and treatment of children presenting with symptoms of a myelopathy. Important components of holistic care may include physiotherapy and occupational therapy, with multidisciplinary team involvement as required (for example psychological support or specialist bowel and bladder teams).

Imaging of Developmental Skull Base Abnormalities.

The skull base is a critical structure in the craniofacial region, supporting the brain and vital facial structures in addition to serving as a passageway for important structures entering and exiting the cranial cavity. This paper will review and highlight some of the embryology, developmental anatomy, including ossification, and related abnormalities of the anterior, central and posterior skull base using illustrative cases and tables. Pathologies such as dermoids/epidermoids, cephaloceles, nasal gliomas, glioneuronal heterotopias, various notochordal remnants, persistent craniopharyngeal canal, teratomas, platybasia, basilar invagination, clival anomalies and Chiari malformations will be discussed. Developmental pearls and pitfalls will also be highlighted.

Systemic Inflammation Is Associated With Neurologic Involvement in Pediatric Inflammatory Multisystem Syndrome Associated With SARS-CoV-2.

OBJECTIVE: Pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) is a severe immune-mediated disorder. We aim to report the neurologic features of children with PIMS-TS. METHODS: We identified children presenting to a large children's hospital with PIMS-TS from March to June 2020 and performed a retrospective medical note review, identifying clinical and investigative features alongside short-term outcome of children presenting with neurologic symptoms. RESULTS: Seventy-five patients with PIMS-TS were identified, 9 (12%) had neurologic involvement: altered conciseness (3), behavioral changes (3), focal neurology deficits (2), persistent headaches (2), hallucinations (2), excessive sleepiness (1), and new-onset focal seizures (1). Four patients had cranial images abnormalities. At 3-month follow-up, 1 child had died, 1 had hemiparesis, 3 had behavioral changes, and 4 completely recovered. Systemic inflammatory and prothrombotic markers were higher in patients with neurologic involvement (mean highest CRP 267 vs 202 mg/L, p = 0.05; procalcitonin 30.65 vs 13.11 µg/L, p = 0.04; fibrinogen 7.04 vs 6.17 g/L, p = 0.07; d-dimers 19.68 vs 7.35 mg/L, p = 0.005). Among patients with neurologic involvement, these markers were higher in those without full recovery at 3 months (ferritin 2284 vs 283 µg/L, p = 0.05; d-dimers 30.34 vs 6.37 mg/L, p = 0.04). Patients with and without neurologic involvement shared similar risk factors for PIMS-TS (Black, Asian and Minority Ethnic ethnicity 78% vs 70%, obese/overweight 56% vs 42%). CONCLUSIONS: Broad neurologic features were found in 12% patients with PIMS-TS. By 3-month follow-up, half of these surviving children had recovered fully without neurologic impairment. Significantly higher systemic inflammatory markers were identified in children with neurologic involvement and in those who had not recovered fully.

Achondroplasia Foramen Magnum Score: screening infants for stenosis.

BACKGROUND: Achondroplasia is associated with foramen magnum stenosis (FMS) and significant risk of morbidity and sudden death in infants. A sensitive and reliable method of detecting infants who require decompressive surgery is required. This study aims to describe the incidence and severity of FMS in an unselected, sequential series of infants using a novel MRI score and retrospectively correlate severity with clinical examination and cardiorespiratory sleep (CRS) studies. METHODS: The Achondroplasia Foramen Magnum Score (AFMS) was developed and scores were retrospectively correlated with clinical and CRS data over a 3-year period. RESULTS: Of 36 infants (M:F, 18:18), 2 (5.6%) did not have FMS (AFMS0); 13 (36.1%) had FMS with preservation of the cerebrospinal fluid (CSF) spaces (AFMS1); 3 (8.3%) had FMS with loss of the CSF space but no spinal cord distortion (AFMS2); 13 (36.1%) had FMS with flattening of the cervical cord without signal change (AFMS3); and 5 (13.9%) had FMS resulting in cervical cord signal change (AFMS4). Mean Total Apnea and Hypopnea Index (TAHI) for AFMS0-4 was 3.4, 6.41, 2.97, 10.5 and 25.8, respectively. Severe TAHI had a specificity of 89% but only a 59% sensitivity for AFMS3-4. Neurological examination was normal in 34/36 (94%) patients. Overall, 9/36 (25%) infants required neurosurgery with minimal surgical complications. CONCLUSIONS: Clinical examination and CRS have a low sensitivity for predicting the effects of foramen stenosis on the spinal cord. Routine screening with MRI using AFMS can aid in detecting early spinal cord changes and has the potential to reduce infant morbidity and mortality.

Idiopathic Hypertrophic Pachymeningitis: Does Earlier Treatment Improve Outcome?

Background/goal: Hypertrophic pachymeningitis is a rare chronic inflammatory disorder characterized by marked fibrous thickening of the cerebral and/or spinal dura mater. This condition has largely been reported in adults, but there are very few reports in children. METHODS: We describe a 14-year-old boy with idiopathic hypertrophic pachymeningitis, who presented with deteriorating vision on a background of severe headache. We evaluated pediatric cases of hypertrophic pachymeningitis and compared treatments and their relation to outcomes. RESULTS: There are only eleven pediatric cases of hypertrophic pachymeningitis reported in the literature. In the patients treated with steroids either at presentation or subsequent relapses, a good response was reported. In the cases with delayed initiation of steroid treatment, this was often related to an incomplete recovery. In our patient, this delay may have contributed to his poor visual outcome. CONCLUSIONS: Early initiation of steroid treatment in children with idiopathic hypertrophic pachymeningitis may improve outcomes.

Progress in the Management of Paediatric-Onset Multiple Sclerosis.

Considerable progress has been made in the understanding and treatment of paediatric-onset multiple sclerosis (POMS); how this has translated into more effective care is less well understood. Here, we evaluate how recent advances have affected patient management and outcomes with a retrospective review of POMS patients managed at two paediatric neuroimmunology centres. Two cohorts, seen within a decade, were compared to investigate associations between management approaches and outcomes. Demographic, clinical and neurocognitive data were extracted from case notes and analysed. Of 51 patients, 24 were seen during the period 2007-2010 and 27 during the period 2015-2016. Median age at onset was 13.7 years; time from symptom onset to diagnosis was 9 months. Disease-modifying therapies were commenced in 19 earlier-cohort and 24 later-cohort patients. Median time from diagnosis to treatment was 9 months for earlier vs. 3.5 months in later patients (p = 0.013). A wider variety of treatments were used in the later cohort (four medications earlier vs. seven in the later and two clinical trials), with increased quality of life and neurocognitive monitoring (8% vs. 48% completed PedsQL quality of life inventory; 58% vs. 89% completed neurocognitive assessment). In both cohorts, patients were responsive to disease-modifying therapy (mean annualised relapse rate pre-treatment 2.7 vs. 1.7, mean post-treatment 0.74 vs. 0.37 in earlier vs. later cohorts). In conclusion, over the years, POMS patients were treated sooner with a wider variety of medications and monitored more comprehensively. However, this hugely uncontrolled cohort did not allow us to identify key determinants for the improvements observed.

Monogenetic Stroke Syndromes in Children and Young Adults.

OBJECTIVE. The purpose of this article is to review the characteristic CT and MRI findings associated with monogenetic causes of ischemic and hemorrhagic stroke in children and young adults. CONCLUSION. Ischemic and hemorrhagic stroke in children and young adults remains a common cause of acquired disability but is underrecognized. Brain parenchymal and vascular imaging is commonly performed as part of the comprehensive evaluation of young patients presenting with stroke. Familiarity with these patterns of disease enables early recognition of an underlying inherited condition.