Severe atypical Lemierre syndrome caused by methicillin-sensitive Staphylococcus aureus: Two pediatric case reports.

BACKGROUND: Lemierre syndrome is typically associated with ear, nose, and throat (ENT) infections caused by Fusobacterium necrophorum. Since 2002, cases of atypical Lemierre-like syndrome secondary to Staphylococcus aureus have been reported. CASES: We report two pediatric cases of atypical Lemierre syndrome with a similar presentation: exophthalmia, absence of pharyngitis, metastatic lung infection, and intracranial venous sinus thrombosis. Both patients had a favorable outcome following treatment with antibiotics, anticoagulation, and corticosteroids. CONCLUSION: Regular therapeutic monitoring of antibiotic levels helped to optimize antimicrobial treatment in both cases.

Noninvasive Follow-up Imaging of Ruptured Pediatric Brain AVMs Using Arterial Spin-Labeling.

BACKGROUND AND PURPOSE: Brain AVMs represent the main etiology of pediatric intracranial hemorrhage. Noninvasive imaging techniques to monitor the treatment effect of brain AVMs remain an unmet need. In a large cohort of pediatric ruptured brain AVMs, we aimed to investigate the role of arterial spin-labeling for the longitudinal follow-up during treatment and after complete obliteration by analyzing CBF variations across treatment sessions. MATERIALS AND METHODS: Consecutive patients with ruptured brain AVMs referred to a pediatric quaternary care center were prospectively included in a registry that was retrospectively queried for children treated between 2011 and 2019 with unimodal or multimodal treatment (surgery, radiosurgery, embolization). We included children who underwent an arterial spin-labeling sequence before and after treatment and a follow-up DSA. CBF variations were analyzed in univariable analyses. RESULTS: Fifty-nine children with 105 distinct treatment sessions were included. The median CBF variation after treatment was -43 mL/100 mg/min (interquartile range, -102-5.5), significantly lower after complete nidal surgical resection. Following radiosurgery, patients who were healed on the last DSA follow-up demonstrated a greater CBF decrease on intercurrent MR imaging, compared with patients with a persisting shunt at last follow-up (mean, -62 [SD, 61] mL/100 mg/min versus -17 [SD, 40.1] mL/100 mg/min; P = .02). In children with obliterated AVMs, recurrences occurred in 12% and resulted in a constant increase in CBF (mean, +89 [SD, 77] mL/100 mg/min). CONCLUSIONS: Our results contribute data on the role of noninvasive arterial spin-labeling monitoring of the response to treatment or follow-up after obliteration of pediatric AVMs. Future research may help to better delineate how arterial spin-labeling can assist in decisions regarding the optimal timing for DSA.

Infant botulism: Report of a misleading case and important key messages.

Infant botulism is a rare and life-threatening disease caused by the inhalation of Clostridium botulinum spores and differs from adult forms. We report the case of infant botulism in a 4-month-old boy who was exclusively breastfed without any consumption of honey. He presented with severe and acute encephalo-myelo-radiculitis. The patient was treated without success for suspected "postviral" central nervous system inflammatory disease. The diagnosis was eventually made 20 days after the onset of symptoms on the basis of a stool sample. Recovery was complete. Infant botulism should be suspected when infants present with acute flaccid paralysis or brainstem weakness and specific immunoglobulins should be administered.

Risk Factors for Early Brain AVM Rupture: Cohort Study of Pediatric and Adult Patients.

BACKGROUND AND PURPOSE: Whether architectural characteristics of ruptured brain AVMs vary across the life span is unknown. We aimed to identify angioarchitectural features associated with brain AVMs ruptured early in life. MATERIALS AND METHODS: Patients with ruptured brain AVMs referred to 2 distinct academic centers between 2000 and 2018 were pooled and retrospectively analyzed. Imaging was retrospectively reviewed for angioarchitectural characteristics, including nidus size, location, Spetzler-Martin grade, venous drainage, and arterial or nidal aneurysm. Angioarchitecture variations across age groups were analyzed using uni- and multivariable models; then cohorts were pooled and analyzed using Kaplan-Meier and Cox models to determine factors associated with earlier rupture. RESULTS: Among 320 included patients, 122 children (mean age, 9.8 ± 3.8 years) and 198 adults (mean age, 43.3 ± 15.7 years) were analyzed. Pediatric brain AVMs were more frequently deeply located (56.3% versus 21.2%, P < .001), with a larger nidus (24.2 versus 18.9 mm, P = .002), were less frequently nidal (15.9% versus 23.5%, P = .03) and arterial aneurysms (2.7% versus 17.9%, P < .001), and had similar drainage patterns or Spetzler-Martin grades. In the fully adjusted Cox model, supratentorial, deep brain AVM locations (adjusted relative risk, 1.19; 95% CI, 1.01-1.41; P = .03 and adjusted relative risk, 1.43; 95% CI, 1.22-1.67; P < .001, respectively) and exclusively deep venous drainage (adjusted relative risk, 1.46, 95% CI, 1.21-1.76; P < .001) were associated with earlier rupture, whereas arterial or nidal aneurysms were associated with rupture later in life. CONCLUSIONS: The angioarchitecture of ruptured brain AVMs significantly varies across the life span. These distinct features may help to guide treatment decisions for patients with unruptured AVMs.

Arterial ischemic stroke in non-neonate children: Diagnostic and therapeutic specificities.

Pediatric arterial ischemic stroke (AIS) is a severe condition, with long-lasting devastating consequences on motor and cognitive abilities, academic and social inclusion, and global life projects. Awareness about initial symptoms, implementation of pediatric stroke code protocols using MRI first and only and adapted management in the acute phase, individually tailored recanalization treatment strategies, and multidisciplinary rehabilitation programs with specific goal-centered actions are the key elements to improve pediatric AIS management and outcomes. The main cause of pediatric AIS is focal cerebral arteriopathy, a condition with unilateral focal stenosis and time-limited course requiring specific management. Sickle cell disease and moyamoya angiopathy patients need adapted screening and therapeutics.

The role of the neuropediatrician in pediatric intensive care unit: Diagnosis, therapeutics and major participation in collaborative multidisciplinary deliberations about life-sustaining treatments' withdrawal.

BACKGROUND: In Pediatric Intensive Care Unit (PICU) two types of population require the intervention of neuropediatricians (NP): chronic brain diseases' patients who face repetitive and prolonged hospitalizations, and patients with acute brain failure facing the risk of potential neurologic sequelae, and both conditions may result in a limitation of life-sustaining treatments (LLST) decision. OBJECTIVE: To assess NP's involvement in LLST decisions within the PICU of a tertiary hospital. METHOD: Retrospective study of medical reports of patients hospitalized during 2014 in the Necker-Hospital PICU. Patients were selected using keywords ("cardiorespiratory arrest", "death", "withdrawal of treatment", "palliative care", "acute brain failure", or "chronic neurological disease"), and/or if they were assessed by a NP during the hospitalization. Demographic and medical data were analysed, including the NP's assessment and data about Collaborative Multidisciplinary Deliberation (CMD) to discuss potential LLST. RESULTS: Among 1160 children, 274 patients were included and 142 (56%) were assessed by a NP during their hospitalization for diagnosis (n = 55) and/or treatment (n = 95) management. NP was required for 59%-100% of patients with neurological acute failure, and for 14-44% of patients with extra neurological failure. A LLST decision was taken after a CMD for 27 (9.8%) of them, and a NP was involved in 19/27 (70%) of these decisions that occurred during the hospitalization (n = 19) or before (n = 8).12 patients died thereafter the LLST decision (40% of the 30 dead patients). CONCLUSION: NP are clearly involved in the decision-process of LLST for patients admitted in PICU, claiming for close collaboration to improve current practices and the quality of the care provided to children.

Perspectives in neonatal and childhood arterial ischemic stroke.

INTRODUCTION: Over the last decade considerable advances have been made in the identification, understanding and management of pediatric arterial ischemic stroke. Such increasing knowledge has also brought new perspectives and interrogations in the current acute and rehabilitative care of these patients. Areas covered: In developed countries, focal cerebral arteriopathy is one of the most common causes of arterial ischemic stroke in childhood and imaging features are well characterized. However, there are ongoing debates regarding its underlying mechanisms, natural evolution and proper management. The implementation of thrombolytic therapy in acute pediatric stroke has been shown to be efficient in anecdotal cases but is still limited by a number of caveats, even in large tertiary centers. Finally, neonatal stroke represents a unique circumstance of possible early intervention before the onset of any neurological disability but this appears meaningful only in a selective group of neonates. Expert commentary: While perinatal stroke, a leading cause of cerebral palsy, appears to be multifactorial, a large number of childhood ischemic stroke are probably essentially triggered by infectious factors leading to vessel wall damage. Current research is aiming at better identifying risk factors in both conditions, and to define optimal acute and preventive therapeutic strategies in order to reduce significant long-term morbidity.

Cerebral Blood Flow Improvement after Indirect Revascularization for Pediatric Moyamoya Disease: A Statistical Analysis of Arterial Spin-Labeling MRI.

BACKGROUND AND PURPOSE: The severity of Moyamoya disease is generally scaled with conventional angiography and nuclear medicine. Arterial spin-labeling MR imaging is now acknowledged for the noninvasive quantification of cerebral blood flow. This study aimed to analyze CBF modifications with statistical parametric mapping of arterial spin-labeling MR imaging in children undergoing an operation for Moyamoya disease. MATERIALS AND METHODS: We included 15 children treated by indirect cerebral revascularization with multiple burr-holes between 2011 and 2013. Arterial spin-labeling MR imaging and T1 sequences were then analyzed under SPM8, according to the general linear model, before and after the operation (3 and 12 months). Voxel-based analysis was performed at the group level, comparing all diseased hemispheres with all normal hemispheres and, at the individual level, comparing each patient with a control group. RESULTS: Group analysis showed statistically significant preoperative hypoperfusion in the MCA territory in the Moyamoya hemispheres and a significant increase of cerebral perfusion in the same territory after revascularization (P < .05 family-wise error-corrected). Before the operation, individual analysis showed significant hypoperfusion for each patient co-localized with the angiographic defect on DSA. All except 1 patient had improvement of CBF after revascularization, correlated with their clinical status. CONCLUSIONS: SPM analysis of arterial spin-labeling MR imaging offers a noninvasive evaluation of preoperative cerebral hemodynamic impairment and an objective assessment of postoperative improvement in children with Moyamoya disease.

[Imaging Moya-Moya disease]. / Imagerie du Moya-Moya.

Moya-Moya disease is a rare arterial occlusive disease affecting the internal carotid artery and its branches. It is found in both pediatric and adult populations, and it may lead to severe clinical presentations such as stroke and intracranial hemorrhage. Several surgical procedures have been developed to improve its clinical outcome. Imaging techniques have a key role in management of Moya-Moya disease, as they are necessary for diagnosis, choice of treatment and follow-up. Although catheter angiography remains the diagnostic gold standard, and nuclear-medicine techniques best perform hemodynamic studies, less invasive imaging techniques have become efficient in serving these purposes. Conventional MRI and MR angiography, as well as MR functional and metabolic studies, are now widely used in each stage of disease management, from diagnosis to follow-up. CT scan and Doppler sonography may also help assess severity of disease and effects of treatment. The aim of this review is to clarify the utility, efficiency and latest developments of each imaging modality in management of Moya-Moya disease.

[Cerebral vasculopathy in pediatric sickle-cell anemia]. / Drépanocytose et atteinte vasculaire cérébrale chez l'enfant.

In children with sickle-cell anemia, cerebral vasculopathy is a frequent and severe complication. It is attributed not only to erythrocyte sickling but also to multiple physiological modifications associated with sickle-cell anemia: platelet and leukocyte activation, endothelial injury and remodeling, coagulation activation, hemolysis and subsequent chronic inflammation, impaired vasomotricity, etc. Intracranial large-vessel remodeling leads to clinical cerebral infarction, whereas microvascular injury and impaired vasoreactivity lead to so-called silent infarcts, which are actually associated with impaired cognitive development. Primary prevention strategies have been developed to screen children for cerebral vasculopathy and to further reduce stroke risk. Annual transcranial Doppler beginning at 2 years of age is recommended, allowing risk stratification. Patients at high risk are enrolled in a monthly transfusion exchange program, which reduces the risk of a first stroke by 90 %. Chronic transfusion therapy has also demonstrated efficacy in preventing a second stroke, as a secondary prevention strategy. Lifelong treatment is recommended, as recurrent stroke has been observed when transfusion is discontinued. The burden of chronic transfusion is heavy for patients. Furthermore, several studies have shown that, despite preventing clinically symptomatic stroke, chronic transfusion therapy may not be effective concerning silent infarct progression. Other therapeutic options are currently being explored to obtain better protection with reduced side effects.

Quality of life and functional outcome in early school-aged children after neonatal stroke: a prospective cohort study.

BACKGROUND: Quality of life (QoL) is recognized internationally as an efficient tool for evaluating health interventions. To our knowledge, QoL has not been specifically assessed in children after neonatal arterial ischemic stroke (AIS). AIM: To study the QoL of early school-aged children who suffered from neonatal AIS, and QoL correlation to functional outcome. METHOD: We conducted a multicenter prospective cohort study as part of a larger study in full-term newborns with symptomatic AIS. Participating families were sent anonymous QoL questionnaires (QUALIN). Functional outcome was measured using the Wee-FIM scale. Healthy controls in the same age range were recruited in public schools. Their primary caregivers filled in the QUALIN questionnaires anonymously. We used Student's t-test and a rank test to compare patients and controls' QoL and functional outcomes. RESULTS: 84 children with neonatal AIS were included. The control group was composed of 74 children, of which ten were later excluded due to chronic conditions. Mean ages and QUALIN median scores did not differ between patients and controls. Median Wee-FIM scores were lower in hemiplegic children than in non-hemiplegic ones (p < 0.001). QoL scores did not seem correlated to functional outcome. INTERPRETATION: Those results could support the presence of a "disability paradox" in young children following neonatal AIS.

[Experts' recommendations: stroke management in the intensive care unit. Pediatric specificities (excluding neonates)]. / Recommandations formalisées d'experts : prise en charge de l'AVC par le réanimateur. Particularités pédiatriques (nouveau-né exclu).

Stroke in children is not rare. Although there are no randomized trials on childhood stroke, except in sickle cell disease patients, several international guidelines have described quality criteria for stroke management in children. Age-adapted management is required, involving collaboration with a pediatric neurologist and hospitalization in a pediatric intensive care or continuous care unit. All symptomatic treatments used in adults can be recommended in children, including homeostasis assessment and maintenance or blood exchange in sickle cell disease patients. Specific treatments such as thrombolysis or mechanical thrombectomy are not recommended in children, except in the framework of clinical trials, but can be beneficial in adolescents. Multidisciplinary decision-making should be the rule in such situations. Adolescents may be managed in adult stroke units. Indications for surgery in children are adapted from adult guidelines. Appropriate management of cerebral venous thrombosis in children is similar to that in adults. The best management possible can be achieved through a multidisciplinary dialogue between the pediatric neurologist and the adult intensivist or neurologist.

Paediatric moyamoya in mainland France: a comprehensive survey of academic neuropaediatric centres.

BACKGROUND: Epidemiological data of paediatric moyamoya disease/syndrome (MMD/MMS) in non-Asian populations are scarce. METHODS: A questionnaire was sent to every French neuropaediatric academic centre to estimate the prevalence, incidence, familial form rate and location of paediatric MMD/MMS cases. Specific paediatric data were also retrieved from the most recent nationwide Japanese study. RESULTS: A 100% response rate was obtained. The prevalence of paediatric MMD/MMS was estimated at 0.39/100,000 children (95% CI: 0.28-0.49), and the incidence was estimated at 0.065/100,000 children/year (95% CI: 0.025-0.12), with 7.5% familial cases. The prevalence was homogenous within the different administrative areas. CONCLUSIONS: This comprehensive survey of MMD/MMS in academic neuropaediatric centres suggests that the prevalence of the disease in children in France is approximately 1/20th of that estimated in Asia.

[Anticoagulant treatment for cerebral venous thromboses in children and newborns. French Society of Pediatric Neurology guidelines]. / Traitement anticoagulant des thromboses veineuses cérébrales de l'enfant et du nouveau-né. Les recommandations de la Société française de neurologie pédiatrique (SFNP).

Anticoagulation is recommended in the acute phase of cerebral venous thrombosis in adults, then for 3-12 months. In children, 2 consensus reports published in 2008 also recommend use of anticoagulants, whereas conclusions diverge for newborns. These consensus reports are based on observational studies, authors' experience, and comparisons with adult pathology. In view of the original studies published since then, the French Society of Pediatric Neurology (Société française de neurologie pédiatrique [SFNP]) wished to update the level of evidence and the knowledge in this domain. The results from the analysis of the literature show that anticoagulation is widely used in pediatrics. It is well-tolerated in children (class I, level of evidence B) and probably in the newborn (class IIa, level of evidence B). In the acute phase of cerebral venous thrombosis, anticoagulation is probably effective in reducing the risk of death in children (class IIa, level of evidence B). It is not possible to draw a conclusion on newborns (class IIb). Over the longer term, anticoagulation is effective in reducing the risk of recurrence (class I, level of evidence B). Since this risk is highly dependent on a number of individual factors (the main ones being the child's age, the cause of the thrombosis, and the kinetics of the sinus recanalization), the duration of anticoagulation should be analyzed individually (class I, level of evidence B). All in all, the convergence of the results, the physiopathologic arguments, and the concordance with the data on adult patients has led to the following recommendations: in the absence of a contra-indication, it is reasonable to propose anticoagulation in the acute phase of cerebral venous thrombosis in children. Prolonging this treatment for 3-6 months is indicated depending on the number of individual factors. In the absence of a contra-indication, anticoagulation may be considered individually in the acute phase of cerebral venous thrombosis in newborns for 6-12 weeks.