Be aware of childhood stroke: Proceedings from EPNS Webinar.

Childhood arterial ischaemic stroke (AIS) is a significant health concern with increasing incidence. This review aims to provide an overview of the current understanding of childhood AIS. The incidence of childhood AIS is on the rise especially in developing countries, likely due to improved awareness and diagnostic capabilities. Aetiology of childhood AIS is multifactorial, with both modifiable risk factors and genetic predisposition playing important roles. Identifying and addressing these risk factors, such as infection, sickle cell disease, and congenital heart defects, is essential in prevention and management. Identifying underlying conditions through genetic testing is important for appropriate management and long-term prognosis. Clinically, distinguishing stroke from stroke mimics can be challenging. Awareness of important stroke mimics, including migraines, seizures, and metabolic disorders, is crucial to avoid misdiagnosis and ensure appropriate treatment. The diagnostic approach to childhood AIS involves a comprehensive "chain of care," including initial assessment, neuroimaging, and laboratory investigations. National guidelines play a pivotal role in standardizing and streamlining the diagnostic process, ensuring prompt and accurate management. Early intervention is critical in the management of childhood AIS. Due to the critical time window, the question if mechanical thrombectomy is feasible and beneficial should be addressed as fast as possible. Early initiation of antiplatelet or anticoagulation therapy and, in select cases, thrombolysis can help restore blood flow and minimize long-term neurological damage. Additionally, rehabilitation should start as soon as possible to optimize recovery and improve functional outcomes. In conclusion, childhood AIS is a growing concern. Understanding the increasing incidence, age distribution, risk factors, clinical presentation, diagnostic approach, and management strategies is crucial for optimized management of these patients.

Inflammatory Type Focal Cerebral Arteriopathy of the Posterior Circulation in Children: A Comparative Cohort Study.

BACKGROUND: Inflammatory type focal cerebral arteriopathy (FCA-i) in the anterior circulation (AC) is well characterized, and the focal cerebral arteriopathy severity score (FCASS) reflects the severity of the disease. We identified cases of FCA-i in the posterior circulation (PC) and adapted the FCASS to describe these cases. METHODS: In this comparative cohort study, patients from the Swiss NeuroPaediatric Stroke Registry with ischemic stroke due to FCA-i between January 2000 and December 2018 were analyzed. A comparison between PC and AC cases regarding pediatric National Institutes of Health Stroke Scale score and pediatric stroke outcome measure and FCASS was performed. We estimated infarct size by the modified pediatric Alberta Stroke Program Early Computed Tomography Score in children with AC stroke and the adapted Bernese posterior diffusion-weighted imaging score in the PC. RESULTS: Thirty-five children with a median age of 6.3 (interquartile range, 2.7-8.2 [95% CI, 0.9-15.6]; 20 male; 57.1%) years with FCA-i were identified. The total incidence rate was 0.15/100 000/year (95% CI, 0.11-0.21). Six had PC-FCA-i. Time to final FCASS was longer in the PC compared with AC; the evolution of FCASS did not differ. Initial pediatric National Institutes of Health Stroke Scale score was higher in children with FCA-i in the PC with a median of 10.0 (interquartile range, 5.75-21.0) compared with 4.5 (interquartile range, 2.0-8.0) in those with AC-FCA-i. Different from the anterior cases, PC infarct volume did not correlate with higher discharge, maximum, or final FCASS scores (Pearson correlation coefficient [r], 0.25, 0.35, and 0.54). CONCLUSIONS: FCA-i also affects the PC. These cases should be included in future investigations into FCA-i. Although it did not correlate with clinical outcomes in our cohort, the modified FCASS may well serve as a marker for the evolution of the arteriopathy in posterior FCA-i.

Focal Cerebral Arteriopathy of Childhood: Clinical and Imaging Correlates.

Background and Purpose: Focal cerebral arteriopathy (FCA) of childhood with unilateral stenosis of the anterior circulation is reported to account for up to one-quarter of childhood arterial ischemic stroke, with stroke recurrence in 25% of cases. Limited knowledge regarding pathophysiology and outcome results in inconsistent treatment of FCA. Methods: Children with arterial ischemic stroke due to FCA between January 1, 2009, and January 1, 2019, were retrospectively identified at our institution which serves the US Pacific Northwest region. Electronic health record data, including neuroimaging studies, were reviewed, and the Pediatric Stroke Outcome Measure at 1 year was determined as the primary clinical end point. Results: Fifteen children were diagnosed with FCA, accounting for 19% of children with cerebral arteriopathies (n=77). Among children with FCA, the median age at the time of stroke was 6.8 years (Q1­Q3, 1.9­14.0 years). Four (20%) patients had worsening stroke, 3 of whom had concurrent infection. Three (20%) FCA cases were treated with steroids, one of whom had worsening stroke. Median Pediatric Stroke Outcome Measure at 1 year was 1.0 (Q1­Q3, 0.6­2.0). Variability in arteriopathy severity was observed within many patients. Patients with more severe arteriopathy using the Focal Cerebral Arteriopathy Severity Score had larger strokes and were more likely to have worsening stroke. The most common long-term neurological deficit was hemiparesis, which was present in 11 (73%) patients and associated with middle cerebral artery arteriopathy and infarcts. Conclusions: FCA may be less common than previously reported. Neuroimaging in FCA can help identify patients at greater risk for worsening stroke.

MRI Vessel Wall Enhancement and Other Imaging Biomarkers in Pediatric Focal Cerebral Arteriopathy-Inflammatory Subtype.

Background and Purpose- Focal cerebral arteriopathy-inflammatory type (FCA-i) is a common cause of pediatric arterial ischemic stroke characterized angiographically by unifocal and unilateral stenosis/irregularity of the large anterior circulation arteries with a presumed inflammatory cause. Arterial vessel wall enhancement (VWE) on vessel wall magnetic resonance imaging is a potential biomarker of inflammation that may improve diagnosis, guide treatment, and predict outcomes in patients with FCA-i. We hypothesized that patients with FCA-i with more severe or extensive VWE would have worse arteriopathy, larger infarcts, worse clinical outcome, and increased risk for infarct progression/recurrence. Methods- Pediatric patients with arterial ischemic stroke, classified as FCA-i, and who underwent vessel wall imaging were retrospectively identified at our institution. Clinical data were reviewed and the Pediatric Stroke Outcome Measure at 1 year was determined as the primary clinical end point. Neuroimaging studies were assessed for infarct size, arteriopathy severity (Focal Cerebral Arteriopathy Severity Score), and VWE. Results- Nine cases of FCA-i with vessel wall imaging were evaluated, and there was a strong correlation between clinical outcome at 1-year with initial infarct volume (Spearman correlation coefficient rho=0.84; P<0.01) and arteriopathy severity (Focal Cerebral Arteriopathy Severity Score; rho=0.85; P<0.01). Patients with infarct progression/recurrence had worse Focal Cerebral Arteriopathy Severity Score at presentation compared with those without progression/recurrence (median [IQR]; 9.0 [8.0-11.8] and 5.0 [4.0-7.0], respectively; P<0.05). On the contrary, measures of VWE were not correlated with arteriopathy severity, infarct size, clinical outcome, or risk of infarct progression/recurrence. Moreover, not all patients with FCA-i demonstrated VWE. Conclusions- VWE may not be a reliable biomarker for the diagnosis or assessment of FCA-i, and future work is needed to assess the utility of vessel wall imaging in pediatric arterial ischemic stroke and FCA-i.

Rufinamide efficacy and association with phenotype and genotype in children with intractable epilepsy: A retrospective single center study.

OBJECTIVE: To assess long-term efficacy and tolerability of rufinamide in children with epilepsy and a broad spectrum of underlying epileptic etiologies. METHODS: Patients with epilepsy treated with rufinamide between 1/1/2009 and 1/1/2018 at Seattle Children's Hospital were included. Data were collected via retrospective chart review. Rufinamide efficacy was defined as seizure reduction from baseline including seizure free, >50% reduction, any reduction, no reduction, or worsening seizures. Pearson's chi-square test was used for statistical analysis. RESULTS: 183 patients (70 females and 113 males) with a broad spectrum of epileptic aetiologies (genetic/metabolic, hypoxic-ischemic, structural and others) were included. 45.9% of the patients had Lennox Gastaut syndrome. Rate of any seizure reduction was at 47.5%, seizure reduction >50% at 35%, and seizure free at 3.3%. Mean rufinamide dosage was 33.9 mg/kg/d (SD = 14.12). Mean duration of treatment was 44.48 months (SD 32.33). Suspected adverse effects occurred at 10.9%, most often as fatigue. Rufinamide achieved better seizure reduction in girls compared to boys [OR = 0.52, 95% CI (0.28, 0.97), p = 0.038]. Seizures were activated in a patient with a SCN1A mutation, fully controlled in a patient with a SCN8A mutation. Patients with certain genetic abnormalities such as DEPDC5, KCNQ2, SPATA5, and 47XYY achieved significant seizure reduction. CONCLUSIONS: Rufinamide is an effective and well-tolerated drug for long-term treatment in pediatric patients with intractable epilepsy. Certain genotypes such as SCN8A showed good response to rufinamide. Girls seemed to respond better than boys.

Geometric morphometrics reveal altered corpus callosum shape in pyridoxine-dependent epilepsy.

OBJECTIVE: To evaluate the features and maturational changes in overall callosal shape in patients with pyridoxine-dependent epilepsy (PDE). METHODS: Measurements were conducted through landmark-based geometric morphometrics applied on cerebral MRIs of patients with PDE and age-matched control subjects. The outline of the corpus callosum was manually traced in the midsagittal plane. Three hundred semi-landmarks along the outline were collected and underwent statistical generalized Procrustes analysis. An allometric regression was applied to evaluate the callosal shape due to growth over time. RESULTS: Thirty-eight patients with PDE and 38 age- and sex-matched control subjects were included. Mean age at the time of the MRI in the patient group was 9.3 years (median 6.3 years, range 0.01-48 years). Significant differences (p < 0.01) in the mean callosal shape between patients and controls were found. The allometric regression model revealed significant shape variations (p < 0.01) between the 2 study groups across the developmental course after controlling for the effect of callosal size on shape. This latter effect turned out to be significant as well (p < 0.001). CONCLUSIONS: Patients with PDE show an altered callosal shape and variations in callosal ontogeny, which are likely secondary to the underlying genetic defect with abnormal function of antiquitin, the product of the ALDH7A1 gene.

Bacteriostatic versus bactericidal antibiotics for patients with serious bacterial infections: systematic review and meta-analysis.

OBJECTIVES: Antibiotics are commonly classified into bactericidal and bacteriostatic agents based on their antimicrobial action. We aimed to assess whether this distinction is clinically relevant. METHODS: OVID MEDLINE, EMBASE, The Cochrane Central Register of Controlled Trials (CENTRAL) and relevant references and conference proceedings using the Web of Science and Scopus databases were searched for randomized controlled trials comparing bactericidal with bacteriostatic antibiotics for treatment of severe infections. Main outcome measures were clinical cure rates and overall mortality. Abstracts of studies selected in the database search were screened by one reviewer; full-text screening and data extraction were performed by three independent reviewers. RESULTS: Thirty-three studies were included. Approximately half of patients were treated with bacteriostatic monotherapy. Infections covered were pneumonia (n=13), skin and soft tissue infections (n=8), intra-abdominal infections (n=4) and others (n=8). Neither clinical cure rates [risk ratio (RR), 0.99; 95% CI, 0.97-1.01; P=0.11] nor mortality rates (RR, 0.91; 95% CI, 0.76-1.08; P=0.28) were different between patients treated with bactericidal drugs and those treated with bacteriostatic drugs. Subgroup analyses showed a benefit for clinical cure rates associated with linezolid and increased mortality associated with tigecycline. In meta-regression, clinical cure rates remained higher in patients treated with linezolid (P=0.01); tigecycline displayed a close to significant association with increased mortality (P=0.05) if compared with other bacteriostatic agents. CONCLUSIONS: The categorization of antibiotics into bacteriostatic and bactericidal is unlikely to be relevant in clinical practice if used for abdominal infections, skin and soft tissue infections and pneumonia. Because we were not able to include studies on meningitis, endocarditis or neutropenia, no conclusion regarding these diseases can be drawn.