Long-term forgetting is independent of age in healthy children and adolescents.

Introduction: In clinical neuropsychology, the phenomenon of accelerated long-term forgetting (ALF) has advanced to be a marker for subtle but clinically relevant memory problems associated with a range of neurological conditions. The normal developmental trajectory of long-term memory, in this case, memory recall after 1 week, and the influence of cognitive variables such as intelligence have not extensively been described, which is a drawback for the use of accelerated long-term forgetting measures in pediatric neuropsychology. Methods: In this clinical observation study, we analyzed the normal developmental trajectory of verbal memory recall after 1 week in healthy children and adolescents. We hypothesized that 1-week recall and 1-week forgetting would be age-dependent and correlate with other cognitive functions such as intelligence and working memory. Sixty-three healthy participants between the ages of 8 and 16 years completed a newly developed auditory verbal learning test (WoMBAT) and the WISC-V intelligence test (General Ability Index, GAI). Using these tests, 1 week recall and 1 week forgetting have been studied in relation to GAI, verbal learning performance, and verbal working memory. Results: Neither 1-week recall nor 1-week forgetting seems to be age-dependent. They are also not significantly predicted by other cognitive functions such as GAI or working memory. Instead, the ability to recall a previously memorized word list after 7 days seems to depend solely on the initial learning capacity. Conclusion: In the clinical setting, this finding can help interpret difficulties in free recall after 7 days or more since they can probably not be attributed to young age or low intelligence.

Impaired episodic verbal memory recall after 1 week and elevated forgetting in children after mild traumatic brain injury - results from a short-term longitudinal study.

Objective: There is preliminary evidence that children after traumatic brain injury (TBI) have accelerated long-term forgetting (ALF), i.e., an adequate learning and memory performance in standardized memory tests, but an excessive rate of forgetting over delays of days or weeks. The main aim of this study was to investigate episodic memory performance, including delayed retrieval 1 week after learning, in children after mild TBI (mTBI). Methods: This prospective study with two time-points (T1: 1 week after injury and T2: 3-6 months after injury), included data of 64 children after mTBI and 57 healthy control children aged between 8 and 16 years. We assessed episodic learning and memory using an auditory word learning test and compared executive functions (interference control, working memory, semantic fluency and flexibility) and divided attention between groups. We explored correlations between memory performance and executive functions. Furthermore, we examined predictive factors for delayed memory retrieval 1 week after learning as well as for forgetting over time. Results: Compared to healthy controls, patients showed an impaired delayed recall and recognition performance 3-6 months after injury. Executive functions, but not divided attention, were reduced in children after mTBI. Furthermore, parents rated episodic memory as impaired 3-6 months after injury. Additionally, verbal learning and group, but not executive functions, were predictive for delayed recall performance at both time-points, whereas forgetting was predicted by group. Discussion: Delayed recall and forgetting over time were significantly different between groups, both post-acutely and in the chronic phase after pediatric mTBI, even in a very mildly injured patient sample. Delayed memory performance should be included in clinical evaluations of episodic memory and further research is needed to understand the mechanisms of ALF.

Baseline characteristics and outcome of stroke patients after endovascular therapy according to previous symptomatic vascular disease and sex.

Aim: The aim of this study was to investigate baseline characteristics and outcome of patients after endovascular therapy (EVT) for acute large vessel occlusion (LVO) in relation to their history of symptomatic vascular disease and sex. Methods: Consecutive EVT-eligible patients with LVO in the anterior circulation admitted to our stroke center between 04/2015 and 04/2020 were included in this observational cohort study. All patients were treated according to a standardized acute ischaemic stroke (AIS) protocol. Baseline characteristics and successful reperfusion, recurrent/progressive in-hospital ischaemic stroke, symptomatic in-hospital intracranial hemorrhage, death at discharge and at 3 months, and functional outcome at 3 months were analyzed according to previous symptomatic vascular disease and sex. Results: 995 patients with LVO in the anterior circulation (49.4% women, median age 76 years, median admission NIHSS score 14) were included. Patients with multiple vs. no previous vascular events showed higher mortality at discharge (20% vs. 9.3%, age/sex - adjustedOR = 1.43, p = 0.030) and less independency at 3 months (28.8% vs. 48.8%, age/sex - adjustedOR = 0.72, p = 0.020). All patients and men alone with one or multiple vs. patients and men with no previous vascular events showed more recurrent/progressive in-hospital ischaemic strokes (19.9% vs. 6.4% in all patients, age/sex - adjustedOR = 1.76, p = 0.028) (16.7% vs. 5.8% in men, age-adjustedOR = 2.20, p = 0.035). Men vs. women showed more in-hospital symptomatic intracranial hemorrhage among patients with one or multiple vs. no previous vascular events (23.7% vs. 6.6% in men and 15.4% vs. 5.5% in women, OR = 2.32, p = 0.035/age - adjustedOR = 2.36, p = 0.035). Conclusions: Previous vascular events increased the risk of in-hospital complications and poorer outcome in the analyzed patients with EVT-eligible LVO-AIS. Our findings may support risk assessment in these stroke patients and could contribute to the design of future studies.

Different trajectories of post-concussive symptom subscales after pediatric mild traumatic brain injury: Data from a prospective longitudinal study.

PURPOSE: The aim of this study was to investigate the trajectory of parent-rated post-concussive symptoms (PCS), attentional performance and participation within 6 months in children after mild traumatic brain injury (mTBI). METHODS: For this prospective longitudinal study, we included data on 64 children after mTBI and 57 healthy control children (age 8-16 years). Parents rated PCS using the Post-Concussion Symptom Inventory (PCSI) immediately (T0), 1 week (T1), and 3-6 months after injury (T2). Attentional performance (alertness, selective and divided attention) was measured using the Test of Attentional Performance (TAP) at T1 and T2 and participation was measured using the Child and Adolescent Scale of Participation (CASP) at T2. RESULTS: Friedman tests showed different trajectories of PCS subscales over time: Compared to pre-injury level, the amount of somatic and cognitive PCS was still elevated at T1, while emotional PCS at T1 were already comparable to pre-injury level. The rating of sleep-related PCS at T2 was significantly elevated compared to the pre-injury rating. Quade ANCOVAs indicated group differences in PCS subscales between patients and controls at T1, but not at T2. Patients and controls showed a similar performance in tests of attention at T1 and T2, but parental rating of participation at school was significantly reduced. Although cognitive PCS and attention were not correlated, there were significantly negative Spearman correlations between participation at home and pre-injury and concurrent PCS at T2. CONCLUSIONS: Our data imply that sleep-related PCS are still elevated weeks after injury and are thus a target for interventions after mTBI.

Processing speed and its association with working memory and episodic memory 3-6 months after pediatric mild traumatic brain injury.

OBJECTIVE: Following mild traumatic brain injury (mTBI), children show reduced processing speed (PS). Evidence suggests that slowed PS after TBI is associated with working memory deficits. Our aim was to investigate several forms of PS and to examine its impact on working and episodic memory performance in children after mTBI. METHOD: We included data of 64 children after mTBI and 57 healthy control children aged 8-16 years. PS (Color Naming, Coding, Symbol Search, Alertness) was compared between groups 1 week (T1) and 3-6 months (T2) after the injury; working and episodic memory outcome was compared between groups at T2. RESULTS: Alertness at T1 and Color Naming at T1 and T2 were significantly reduced following mTBI compared to controls, although most group differences in PS disappeared when patients with previous impairments and mTBI were excluded. PS was predictive for episodic and working memory performance 3-6 months after injury, whereas group was a significant predictor of working memory. CONCLUSIONS: Compared to healthy controls, children after mTBI showed reduced performance in verbal PS, which was associated with working memory. In children who are symptomatic after mTBI, diagnostic screening of PS could be helpful in identifying patients that could profit from speed-improving strategies.

Protocol on establishing a national disease registry-Swiss Pediatric Inflammatory Brain Disease Registry.

BACKGROUND: Pediatric-onset inflammatory brain diseases are a group of potentially life-threatening central nervous system disorders. Overall, pediatric-onset inflammatory brain diseases are rare and therefore difficult to study. Patient registries are well suited to study the natural history of (rare) diseases and have markedly advanced the knowledge on pediatric-onset inflammatory brain diseases in other countries. Following their example, we established a national pediatric-onset inflammatory brain disease registry in Switzerland (Swiss-Ped-IBrainD). AIMS: The Registry aims to describe epidemiology, demographics, diagnostics, management, and treatment, since these areas remain understudied in Switzerland. Additionally, we want to promote research by fostering the knowledge exchange between study centers and setting up studies such as national quality of life surveys. We further aim to facilitate the access to national and international studies for patients with a pediatric-onset inflammatory brain disease living and/or treated in Switzerland. METHODS: The Swiss-Ped-IBrainD is a multicentric, population-based, observational cohort study (IRB number: 2019-00377) collaborating with 11 neuropediatric centers in Switzerland. Patient screening, information and recruitment is mainly conducted by the local principal investigators. The data collection is organized centrally by the Executive Office of the registry. The collected data is purely observational. Medical records are the primary data source. All patients who have been diagnosed with a pediatric-onset inflammatory brain disease since 2005 are eligible. We aim to include all pediatric-onset inflammatory brain disease patients living and/or treated in Switzerland who meet the inclusion criteria. Considering existing literature and our single-center experience we anticipate 300-400 eligible patients. STATUS: Currently, all 11 neuropediatric centers have been initiated and are recruiting. As of the first of May 2023, we have identified 275 eligible participants and obtained informed consent from 101 patients and/or families. None of the informed patients and/or families have refused participation.

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.

Delayed episodic memory recall after one week is associated with executive functions and divided attention in pediatric epilepsy patients.

AIM: Recent studies suggest that although children with epilepsy may show normal learning and memory performance, accelerated long-term forgetting (ALF) may become evident over time. Our study examined associations between delayed episodic memory performance (recall 1-week after learning) and executive functions. METHOD: A consecutive sample of children with a diagnosis of idiopathic epilepsy with focal or generalized seizures, without morphologic or metabolic abnormalities (n = 20, mean age: 11.70 years) was compared to an IQ-matched healthy control group (n = 20, mean age: 11.55 years). We also assessed parents' and children's rating of forgetting in everyday life and explored its association with delayed episodic memory recall. RESULTS: Similar to results from recent studies of pediatric patients with temporal lobe epilepsy or genetic generalized epilepsy, our pediatric epilepsy patients showed a significantly elevated recall loss over time, although verbal learning, immediate and 30-minute recall was comparable to the matched control group. Additionally, delayed memory recall in patients was moderately associated with their subjective rating of forgetting, as well as with executive functions (verbal fluency and switching) and divided attention. INTERPRETATION: We assume that executive functions play a crucial role in deep memory encoding, facilitating stronger and more enduring memory traces. Given that approximately 20% of epilepsy patients - compared to a healthy reference sample - had a significantly reduced delayed recall and due to the clinical relevance of long-term memory, age-appropriate standard norms for free memory recall after 1-week are desirable.

Acute flaccid myelitis in Switzerland - association with enterovirus D68.

Poliomyelitis-like acute flaccid myelitis associated with enterovirus D68 (EV-D68) has emerged globally during the past decade. Here we describe the first documented case reported from Switzerland, and a second, suspected case occurring in temporal association. AFM occurs primarily in children, is usually heralded by a febrile, respiratory prodrome followed by acute-onset, usually asymmetrical, limb weakness with some predilection for the upper extremities, and respiratory muscle compromise in one third of reported cases. There is no specific therapy and the majority of cases result in permanent neurological sequelae. A comprehensive diagnostic workup and timely reporting to the health authorities are essential. Surveillance of respiratory and stool samples for EV-D68 and other neurotropic enteroviruses is in place in several European countries and warrants consideration in Switzerland. This could entail the extension of the poliomyelitis surveillance program of the Federal Office of Public Health by monitoring and enteroviral typing of respiratory samples from patients with acute flaccid paralysis.

Systematic Review of Accelerated Long-term Forgetting in Children and Adolescents With Neuropediatric Diseases.

Purpose of Review: Accelerated long-term forgetting (ALF) describes the phenomenon of normal learning and memory performance after short delays, but greater forgetting after longer delays, which is not objectified in standardized memory tests. The topic is attracting increasing interest due to its clinical importance. Studies investigating pediatric ALF remain rare, and no systematic review exists. Recent Findings: Based on our systematic literature search, 12 studies were found. Although most studies investigated ALF in children with epilepsy (n = 9), there is also evidence of ALF in children after traumatic brain injury (n = 1) and 22q11.2 deletion syndrome (n = 1). Summary: To date, only a dozen of studies have investigated pediatric ALF. There is evidence that ALF is not an epilepsy-specific disorder, replicating findings of studies with adult patients. Because ALF is missed using standardized assessments, we propose to add delayed time points of testing memory performance.

Fatigue in Post-COVID-19 Syndrome: Clinical Phenomenology, Comorbidities and Association With Initial Course of COVID-19.

Introduction: Post-COVID-19 syndrome affects approximately 10-25% of people suffering from COVID-19 infection, irrespective of initial COVID-19 severity. Fatigue is one of the major symptoms, occurring in 30-90% of people with post-COVID-19 syndrome. This study aims at describing factors associated with fatigue in people with Post-COVID-19 seen in our newly established Post-Covid clinic. Methods: This retrospective single center study included 42 consecutive patients suffering from Post-COVID-19 syndrome treated at the Department of Neurology, University Hospital Bern, between 11/2020 and05/2021. Clinical phenomenology of Post-COVID-19 syndrome with a special focus on fatigue and risk factor identification was performed using Mann-Whitney U Test, Pearson Correlation, and Chi-Quadrat-Test. Results: Fatigue (90.5%) was the most prevalent Post-COVID-19 symptom followed by depressive mood (52.4%) and sleep disturbance (47.6%). Fatigue was in mean severe (Fatigue severity scale (FSS) mean 5.5 points (95% Confidence interval (95CI) 5.1 - 5.9, range .9 - 6.9, n = 40), and it was unrelated to age, COVID-19 severity or sex. The only related factors with fatigue severity were daytime sleepiness and depressed mood. Conclusion: Fatigue is the main symptom of the Post-COVID-19 syndrome in our cohort. Further studies describing this syndrome are needed to prepare the healthcare systems for the challenge of treating patients with Post-COVID-19 syndrome.

Computerized Symbol Digit Modalities Test in a Swiss Pediatric Cohort - Part 2: Clinical Implementation.

BACKGROUND: Information processing speed (IPS) is a marker for cognitive function. It is associated with neural maturation and increases during development. Traditionally, IPS is measured using paper and pencil tasks requiring fine motor skills. Such skills are often impaired in patients with neurological conditions. Therefore, an alternative that does not need motor dexterity is desirable. One option is the computerized symbol digit modalities test (c-SDMT), which requires the patient to verbally associate numbers with symbols. METHODS: Eighty-six participants (8-16 years old; 45 male; 48 inpatients) were examined, 38 healthy and 48 hospitalized for a non-neurological disease. All participants performed the written SDMT, c-SDMT, and the Test of Non-verbal Intelligence Fourth Edition (TONI-4). Statistical analyses included a multivariate analysis of covariance (MANCOVA) for the effects of intelligence (IQ) and hospitalization on the performance of the SDMT and c-SDMT. A repeated measures analysis of variance (repeated measures ANOVA) was used to compare performance across c-SDMT trials between inpatients and outpatients. RESULTS: The MANCOVA showed that hospitalization had a significant effect on IPS when measured with the SDMT (p = 0.04) but not with the c-SDMT (p = 0.68), while IQ (p = 0.92) had no effect on IPS. Age (p < 0.001) was the best predictor of performance of both tests. The repeated measures ANOVA revealed no significant difference in within-test performance (p = 0.06) between outpatient and inpatient participants in the c-SDMT. CONCLUSION: Performance of the c-SDMT is not confounded by hospitalization and gives within-test information. As a valid and reliable measure of IPS for children and adolescents, it is suitable for use in both inpatient and outpatient populations.

Computerized Symbol Digit Modalities Test in a Swiss Pediatric Cohort Part 1: Validation.

OBJECTIVE: The objective of this study was to validate the computerized Symbol Digit Modalities Test (c-SDMT) in a Swiss pediatric cohort, in comparing the Swiss sample to the Canadian norms. Secondly, we evaluated sex effects, age-effects, and test-retest reliability of the c-SDMT in comparison to values obtained for the paper and pencil version of the Symbol Digit Modalities Test (SDMT). METHODS: This longitudinal observational study was conducted in a single-center setting at the University Children's Hospital of Bern. Our cohort consisted of 86 children (45 male and 41 female) aged from 8 to 16 years. The cohort included both healthy participants (n = 38) and patients (n = 48) hospitalized for a non-neurological disease. Forty eight participants were assessed during two testing sessions with the SDMT and the c-SDMT. RESULTS: Test-retest reliability was high in both tests (SDMT: ICC = 0.89, c-SDMT: ICC = 0.90). A reliable change index was calculated for the SDMT (RCIp = -3.18, 14.01) and the c-SDMT (RCIp = -5.45, 1.46) corrected for practice effects. While a significant age effect on information processing speed was observed, no such effect was found for sex. When data on the c-SDMT performance of the Swiss cohort was compared with that from a Canadian cohort, no significant difference was found for the mean time per trial in any age group. Norm values for age groups between 8 and 16 years in the Swiss cohort were established. CONCLUSION: Norms for the c-SDMT between the Swiss and the Canadian cohort were comparable. The c-SDMT is a valid alternative to the SDMT. It is a feasible and easy to administer bedside tool due to high reliability and the lack of motor demands.

Evaluation of diagnostic criteria and red flags of myelin oligodendrocyte glycoprotein encephalomyelitis in a clinical routine cohort.

AIMS: Myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) have been proposed to define "MOG encephalomyelitis" (MOG-EM), with published diagnostic and "red flag" criteria. We aimed to evaluate these criteria in a routine clinical setting. METHODS: We retrospectively analyzed patients with borderline/positive MOG-IgG and applied the diagnostic and red flag criteria to determine likelihood of MOG-EM diagnosis. Para-/clinical parameters were described and analyzed with chi-square test. RESULTS: In total, 37 patients fulfilled MOG-EM diagnostic criteria (female-to-male ratio: 1.6:1, median onset age: 28.0 years [IQR 18.5-40.5], n = 8 with pediatric onset). In 24/37, red flags were present, predominantly MOG-IgG at assay cutoff and/or MRI lesions suggestive of multiple sclerosis (MS). As proposed in the consensus criteria, these patients should rather be described as "possible" MOG-EM. Of these, we classified 13 patients as "unlikely" MOG-EM in the presence of the red flag "borderline MOG-IgG" with negative MOG-IgG retest or coincidence of ≥1 additional red flag. This group mainly consisted of patients diagnosed with MS (n = 11). Frequency of cerebrospinal fluid (CSF-)-specific oligoclonal bands (OCB) is significantly lower in definite vs possible and unlikely MOG-EM (P = .0005). CONCLUSION: Evaluation of diagnostic and red flag criteria, MOG-IgG retesting (incl. change of assay), and CSF-specific OCB are relevant in clinical routine cohorts to differentiate MOG-EM from MS.

Findings in susceptibility weighted imaging in pediatric patients with migraine with aura.

BACKGROUND: Migraine with aura (MwA) in pediatric patients is clinically frequent. Clinically complex symptoms need to be differentiated to exclude mimicking conditions. PURPOSE: We hypothesize that MwA in children induces abnormalities readily visible in perfusion time to peak (TTP) maps as well as non-enhanced susceptibility weighted magnetic resonance imaging (SWI). MATERIALS AND METHODS: Between 2010 and 2018, we retrospectively evaluated symptoms and imaging of consecutive pediatric patients <18 years with MwA. We visually scored abnormalities on SWI and TTP maps in 12 regions of interest on both hemispheres on three axial slices, as normal, slightly, distinctly or severely abnormal. RESULTS: 99 patients (69.7% female), mean age 14.07 y (±2.8) were included. Focally increased deoxygenation (FID) in SWI was present in 61.6%. FID on SWI was dominant for the left hemisphere (60.7% vs. 31.1%, (p < .001)), and in 8.2% symmetric. Side of aura symptoms and contralateral hemispheric imaging alterations in patients with FID correlated significantly (p = .002.). 61 of 99 patients had perfusion MR and 59% of these patients showed focal increase of TTP. Age correlated significantly with FID in SWI (r = -.248, p = .013) and increase of TTP in perfusion (r = -.252, p = .05). Focal abnormalities correlated significantly between SWI and TTP maps. Brain regions most often abnormal were the temporal superior, occipital and fronto-parietal regions. CONCLUSIONS: This study provides confidence in recognizing FID, and linking FID in SWI to acute MwA in pediatric patients. FID phenomenon had a left hemispheric significant dominance, and can be found bilaterally.

Health-Related Quality of Life in Young Adults Following Pediatric Arterial Ischemic Stroke.

Background and Purpose- Pediatric arterial ischemic stroke (AIS) is a rare disease leading to long-lasting neurological sequelae. Little is known about the long-term health-related quality of life (HRQoL) of these patients. The study aims to compare HRQoL in young adults who have had pediatric AIS with a healthy control group. Methods- A cross-sectional study compared self-rated HRQoL, depression, fatigability, and behavior in pediatric stroke survivors to healthy controls. Patients with a confirmed diagnosis of pediatric AIS who were ≥18 years at the time of recruitment and ≥2 years after acute AIS, as well as healthy controls ≥18 years matched for age, sex, and socioeconomic status were included. Primary outcome was HRQoL measured with the Short Form Health Survey. Results- Thirty-three patients (median [interquartile range] aged 22 years [20-26]; 22 males, 67%) and 71 controls (median [interquartile range] aged 23 years [21-25]; 41 males, 58%) were included. Overall, HRQoL, depression, or fatigability did not differ between the patients and the control group. Patients rated themselves lower on the disinhibition scale (P=0.049) and tended to rate themselves lower on the executive dysfunction scale (P=0.076). Patients with a poor outcome 24 months after AIS showed a clear trend toward impairment of executive functioning (P=0.056) and work/productivity in the stroke-specific QoL (P=0.05). Conclusions- Self-rated HRQoL, depression, and fatigability in adult pediatric stroke survivors are comparable to healthy adult peers. A poor outcome 24 months after acute stroke might affect work performance and executive functioning in adulthood.

Posterior Arterial Ischemic Stroke in Childhood.

Background and Purpose- Literature on the clinical manifestation and neuroradiological findings in pediatric patients with posterior circulation arterial ischemic stroke is scarce. This study aims to describe epidemiological features, clinical characteristics, and neuroimaging data on pediatric posterior circulation arterial ischemic stroke in Switzerland using the population-based Swiss Neuropediatric Stroke Registry. Methods- Children aged from 1 month to 16 years presenting with an isolated posterior circulation arterial ischemic stroke between 2000 and 2016 were included. Epidemiology, clinical manifestation, stroke cause, and neuroradiological features were summarized using descriptive statistics. Stroke severity was assessed using the pediatric National Institutes of Health Stroke Scale. Correlation analysis was performed using the Spearman correlation coefficient. Results- Forty-three children with posterior circulation arterial ischemic stroke were included (27 boys [62.8%], median age 7.9 years, interquartile range, 5 to 11.7 years). The incidence of posterior circulation arterial ischemic stroke is Switzerland was 0.183/100 000 and represented 16% of all childhood arterial ischemic strokes. Most patients presented with nonspecific neurological complaints, such as headache (58.1%) and nausea/vomiting (46.5%). The most frequent clinical manifestations were ataxia (58.1%) and motor/sensory hemisyndrome (53.5%/51.2%). Unilateral focal cerebral arteriopathy was the most common cause (11 children, 25.6%). Most infarcts were located in the cerebellum (46.5%) and thalamus (39.5%). A shorter diagnostic delay correlated with more severe stroke symptoms at presentation (rho= -0.365, P=0.016). Conclusions- Pediatric posterior circulation arterial ischemic stroke was caused by focal cerebral arteriopathy in one quarter of the patients in our cohort. The frequently reported nonspecific clinical symptoms, especially when associated with mild neurological findings, risk delaying the diagnosis of stroke. A high index of suspicion and increased awareness are required for timely diagnosis and treatment initiation.

Feasibility, safety, and outcome of recanalization treatment in childhood stroke.

OBJECTIVE: Intravenous thrombolysis and endovascular therapy (IVT/EVT) are evidence-based treatments for adults with arterial ischemic stroke (AIS). However, randomized controlled trials in pediatric patients are lacking. This study aimed to describe feasibility, safety, and outcome of IVT/EVT in children with AIS. METHODS: This retrospective study (01/2000-12/2015) included a multicenter, population-based consecutive cohort of patients aged 1 month to 16 years, diagnosed with AIS and presenting with pediatric National Institutes of Health Stroke Scale (pedNIHSS) ≥ 4. Clinical and radiological data of patients receiving IVT/EVT were compared to those receiving standard care (SC) using linear regression to adjust for potential confounders. EVT included intra-arterial thrombolysis and/or mechanical thrombectomy. Outcome was assessed 6 months after stroke using the pediatric stroke outcome measure (PSOM). RESULTS: Overall, 150 patients (age 7.1 ± 4.9 years, 55 [37%] females) presented with pedNIHSS ≥ 4. Recanalization treatment was performed in 16 (11%), of whom 5 (3%) were treated with IVT and 11 (7%) with EVT. Patients receiving recanalization treatment were older (mean age = 11.0 vs 6.9 years, p = 0.01) and more severely affected (median pedNIHSS = 13.5 vs 8.0, p < 0.001). Death and bleeding complications did not differ between the 2 groups. Median (interquartile range) PSOM 6 months after AIS was 2.5 (1-4.3) and 1 (0-2) in the IVT/EVT and SC groups, respectively (p = 0.014). However, after multiple linear regression analysis, only higher baseline pedNIHSS remained associated with an unfavorable outcome (p < 0.001). INTERPRETATION: Recanalization treatment is feasible and seems to be safe in severely affected pediatric AIS patients. The assessment of efficacy of IVT/EVT in pediatric stroke patients requires larger studies. Ann Neurol 2018;83:1125-1132.

Systematic review and meta-analysis on outcome differences among patients with TICI2b versus TICI3 reperfusions: success revisited.

OBJECTIVE: A reperfusion quality of thrombolysis in cerebral infarction (TICI)≥2b has been set as the therapeutic angiography target for interventions in patients with acute ischaemic stroke. This study addresses whether the distinction between TICI2b and TICI3 reperfusions shows a clinically relevant difference on functional outcome. METHODS: A systematic literature review and meta-analysis was carried out and presented in conformity with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria to test the primary hypothesis that TICI2b and TICI3 reperfusions are associated with different rates of modified Rankin Scale (mRS) ≤2 at day 90. Secondary endpoints included rates of haemorrhagic transformations, mortality and excellent functional outcome (mRS ≤1). Summary estimates of ORs (sOR) with 95% CI were calculated using the inverse variance heterogeneity model accounting for multiple true effect sizes. RESULTS: Fourteen studies on 2379 successfully reperfused patients were included (1131 TICI3, 1248 TICI2b). TICI3 reperfusions were associated with higher rates of functional independence (1.74, 95% CI 1.44 to 2.10) and excellent functional outcomes (2.01, 95% CI 1.60 to 2.53), also after including adjusted estimates. The safety profile of patients with TICI3 was superior, as demonstrated by lower rates of mortality (sOR 0.59, 95% CI 0.37 to 0.92) and symptomatic intracranial haemorrhages (sOR 0.42, 95% CI 0.25 to 0.71). CONCLUSION: TICI3 reperfusions are associated with superior outcome and better safety profiles than TICI2b reperfusions. This effect seems to be independent of time and collaterals. As reperfusion quality is the most important modifiable predictor of patients' outcome, a more conservative definition of successful therapy and further evaluation of treatment approaches geared towards achieving TICI3 reperfusions are desirable.