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.

The "index vein" as a sign for migraine aura in the emergency setting.

Background and objectives To assess the usefulness of the "index vein" for making the diagnosis of migraine aura.Methods 400 patients were included when they: i) presented with an acute neurological deficit, ii) had a brain MRI, and iii) had a discharge diagnosis of migraine aura, ischemic stroke, epileptic seizure or controls (n = 100 per group).Results Compared to stroke (2%), epileptic seizure (4%) and controls (1%), the index vein is more prevalent in migraine aura (17%, p < 0.001). The index vein is highly specific for migraine aura (specificity 97%, 95% CI 95-99). The index vein has a positive predictive value for the diagnosis of migraine aura of 70% (95%CI 48-87). The index vein-score has the ability to diagnose migraine aura with a sensitivity of 94% (95%CI 87.4-97.8) and specificity of 73.5% (95%CI 66.8-79.5) at a cut-off of 4 points.Discussion The index vein serves as a good biomarker for migraine aura in the emergency setting.

Symptomatic visual snow in acute ischemic stroke: A case series.

Visual snow is the main symptom of visual snow syndrome, a disorder of predominantly visual disturbances initially described in patients without abnormalities on ancillary investigations. We present a case series of patients with visual snow in the setting of acute ischemic stroke. The first and second patient reported previous episodic visual snow with migraine attacks. The third patient experienced visual snow for the first time during the ischemic stroke. In the first patient, the ischemic stroke affected the right and left precuneus and the right lingual gyrus. In the second patient, the ischemic stroke was located in the left lingual gyrus, parts of the left fusiform and parahippocampal gyrus, left dorso-lateral thalamus, and left cerebellar hemisphere. In the third patient, occipital pole, trunk of the corpus callosum on the right, right paramedian pons, right cerebellar hemisphere, and vermis were affected. Our case series indicates that the symptom visual snow can be caused by vascular lesions in areas of visual processing. Because patients did not meet criteria for visual snow syndrome, dysfunction in the affected areas might only explain part of the complex pathophysiology of visual snow syndrome.

Minor head trauma in infants - how accurate is cranial ultrasound performed by trained radiologists?

Correct management of infants after minor head trauma is crucial to minimize the risk to miss clinically important traumatic brain injury (ciTBI). Current practices typically involve CT or in-hospital surveillance. Cranial ultrasound (CUS) provides a radiation-free and fast alternative. This study examines the accuracy of radiologist-performed CUS to detect skull fracture (SF) and/or intracranial hemorrhage (ICH). An inconspicuous CUS followed by an uneventful clinical course would allow exclusion of ciTBI with a great certainty. This monocentric, retrospective, observational study analyzed CUS in infants (< 12 months) after minor head trauma at Bern University Children's Hospital, between 7/2013 and 8/2020. The primary outcome was the sensitivity and specificity of CUS in detecting SF and/or ICH by comparison to the clinical course and to additional neuroimaging. Out of a total of 325 patients, 73% (n = 241) had a normal CUS, 17% (n = 54) were found with SF, and ICH was diagnosed in 2.2% patients (n = 7). Two patients needed neurosurgery and three patients deteriorated clinically during surveillance. Additional imaging was performed in 35 patients. The sensitivity of CUS was 93% ([0.83, 0.97] 95% CI) and the specificity 98% ([0.95, 0.99] 95% CI). All false-negative cases originated in missed SF without clinical deterioration; no ICH was missed.  Conclusion: This study shows high accuracy of CUS in exclusion of SF and ICH, which can cause ciTBI. Therefore, CUS offers a reliable method of neuroimaging in infants after minor head trauma and gives reassurance to reduce the duration of in-hospital surveillance. What is Known: • Minor head trauma can cause clinically important traumatic brain injury in infants, and the management of these cases is a challenge for the treating physician. • Cranial ultrasound (CUS) is regularly used in neonatology, but its accuracy after head trauma in infants is controversial. What is New: • CUS performed by a trained radiologist can exclude findings related to clinically important traumatic brain injury (ciTBI) with high sensitivity and specificity. It therefore offers reassurance in the management of infants after minor head trauma.

Long-Term Tumor Control Following Targeted Alpha Therapy (TAT) of Low-Grade Gliomas (LGGs): A New Treatment Paradigm?

The median survival time has been reported to vary between 5 and 8 years in low-grade (WHO grade 2) astrocytoma, and between 10 and 15 years for grade 2 oligodendroglioma. Targeted alpha therapy (TAT), using the modified peptide vector [213Bi]Bi/[225Ac]Ac-DOTA-substance P, has been developed to treat glioblastoma (GBM), a prevalent malignant brain tumor. In order to assess the risk of late neurotoxicity, assuming that reduced tumor cell proliferation and invasion should directly translate into good responses in low-grade gliomas (LGGs), a limited number of patients with diffuse invasive astrocytoma (n = 8) and oligodendroglioma (n = 3) were offered TAT. In two oligodendroglioma patients, TAT was applied as a second-line treatment for tumor progression, 10 years after targeted beta therapy using [90Y]Y-DOTA-substance P. The radiopharmaceutical was locally injected directly into the tumor via a stereotactic insertion of a capsule-catheter system. The activity used for radiolabeling was 2-2.5 GBq of Bismuth-213 and 17 to 35 MBq of Actinium-225, mostly applied in a single fraction. The recurrence-free survival times were in the range of 2 to 16 years (median 11 years) in low-grade astrocytoma (n = 8), in which TAT was administered following a biopsy or tumor debulking. Regarding oligodendroglioma, the recurrence-free survival time was 24 years in the first case treated, and 4 and 5 years in the two second-line cases. In conclusion, TAT leads to long-term tumor control in the majority of patients with LGG, and recurrence has so far not manifested in patients with low-grade (grade 2) astrocytomas who received TAT as a first-line therapy. We conclude that targeted alpha therapy has the potential to become a new treatment paradigm in LGG.

Changes of migraine aura with advancing age of patients.

AIM: Given the similar presentation of migraine aura and acute ischemic stroke, advancing patient age might change the characteristics of migraine with aura (MA) and be clinically important. Clinical data, however, are limited. Experimental studies indicate a decrease in the magnitude of cortical spreading depression (CSD), the pathophysiological correlate of migraine aura, with advancing age. Our study aimed to assess the influence of age on the clinical features of MA. METHODS: Three hundred and forty-three patients were interviewed using a structured questionnaire. The questions covered the headache characteristics and symptom types including the characteristics of the C-criterion, as defined by the International Classification of Headache Disorders 3rd Edition. The association of age with MA characteristics was assessed. RESULTS: The median age was 29 (IQR 28-52) and 235 of the 343 patients were women (69%). Individual symptoms of the C-criterion such as gradual aura spreading over longer than 5 min (P < 0.001), two or more aura symptoms occurring in succession (P = 0.005), duration of at least one MA symptom for longer than 60 min (P = 0.004), and associated headache (P = 0.01) were more frequent in younger patients. The number of symptoms including the C-characteristics decreased with increasing age (P < 0.001). Patients with sensory (P < 0.001), motor (P = 0.004) and speech disturbance (P = 0.02) were younger, and older patients with headache had less photophobia (P = 0.04) and phonophobia (P = 0.03). Sensitivity analyses yielded similar results. CONCLUSION: The frequency of typical characteristics of migraine aura and migraine headache including photophobia and phonophobia decreases with advancing patient age. This might have potentially difficult implications for the diagnosis of MA in the elderly.

Treatment and Outcome in Stroke Patients With Acute M2 Occlusion and Minor Neurological Deficits.

BACKGROUND AND PURPOSE: Treatment in stroke patients with M2 segment occlusion of the middle cerebral artery presenting with mild neurological deficits is a matter of debate. The main purpose was to compare the outcome in patients with a minor stroke and a M2 occlusion. METHODS: Consecutive intravenous thrombolysis (IVT) eligible patients admitted to the Bernese stroke center between January 2005 and January 2020 with acute occlusion of the M2 segment and National Institutes of Health Stroke Scale score ≤5 were included. Outcome was compared between IVT only versus endovascular therapy (EVT) including intra-arterial thrombolysis and mechanical thrombectomy (MT; ±IVT) and between IVT only versus MT only. RESULTS: Among 169 patients (38.5% women, median age 70.2 years), 84 (49.7%) received IVT only and 85 (50.3%) EVT (±IVT), the latter including 39 (45.9%) treated with MT only. Groups were similar in sex, age, vascular risk factors, event cause, or preevent independency. Compared with IVT only, there was no difference in favorable outcome (modified Rankin Scale score, 0-2) for EVT (adjusted odds ratio, 0.96; adjusted P=0.935) or for MT only (adjusted odds ratio, 1.12; adjusted P=0.547) groups. Considering only patients treated after 2015, there was a significantly better 3-month modified Rankin Scale shift (adjusted P=0.032) in the EVT compared with the IVT only group. CONCLUSIONS: Our study demonstrates similar effectiveness of IVT only versus EVT (±IVT), and of IVT only versus MT only in patients with peripheral middle cerebral artery occlusions and minor neurological deficits and indicates a possible benefit of EVT considering only patients treated after 2015. There is an unmet need for randomized controlled trials in this stroke field, including imaging parameters, and more sophisticated evaluation of National Institutes of Health Stroke Scale score subitems, neurocognition, and quality of life neglected by the standard outcome scales such as modified Rankin Scale and National Institutes of Health Stroke Scale score.

Functional topography of the thalamo-cortical system during development and its relation to cognition.

The thalamus has complex connections with the cortex and is involved in various cognitive processes. However, little is known about the age-related changes of thalamo-cortical connections and their relation to cognitive abilities. The present study analyzed resting-state functional connectivity between the thalamus and nine cortical functional networks (default mode network (DMN), posterior DMN, left/right executive, dorsal attention, salience, motor, visual and auditory network) in a healthy human sample (N = 95, aged 5-25 years). Cognitive abilities, including processing speed, selective attention, and cognitive flexibility were assessed using neuropsychological tests. All nine cortical resting-state networks showed functional connections to the thalamus at rest, with no effect for sex (p > 0.05). For the motor, visual, auditory, DMN, posterior DMN, salience and dorsal attention network, we found mainly bilateral thalamic projections in the mediodorsal nucleus, pulvinar and in nuclei of the lateral group. For the right and left lateralized executive network, corresponding lateralized thalamic projections were found. Thalamo-cortical connectivity strength showed significant age-related changes from distinct sub-nuclei of the thalamus to different cortical networks including the visual, DMN, salience and dorsal attention network. Further, connectivity strength of thalamo-cortical networks was associated with cognitive abilities, including processing speed, selective attention and cognitive flexibility. Better cognitive abilities were associated with increased thalamo-cortical connectivity in the pulvinar, mediodorsal nucleus, intralaminar nucleus, and nuclei from the lateral group. Alterations in the integrity of the thalamo-cortical system seem to be crucial for the development of cognitive abilities during brain maturation.

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.

Is Asymmetry of the Pons Associated with Hand Function and Manual Ability after Arterial Ischemic Stroke in Children?

AIM: This study was designed to investigate how the asymmetry of the brain stem is related to hand function and manual ability after arterial ischemic stroke (AIS) diagnosed during childhood. METHOD: Patients diagnosed with AIS during childhood (> 5 years old, diagnosis > 2 years before recruitment) and typically developing peers were recruited by the Swiss Neuropediatric Stroke Registry. Brainstem cross-sectional areas of each side at the level of the pons were measured. Pinch and grip strength were measured with a dynamometer, quality of upper limb movement by the Melbourne Assessment 2 and manual ability by the ABILHAND-kids. An asymmetry index was calculated for all measures (except the ABILHAND-kids). Differences between groups and correlations were calculated using nonparametric statistics. RESULTS: Fourteen AIS survivors without hemiparesis, 10 AIS survivors with hemiparesis, and 47 typically developing peers were assessed. Patients with hemiparesis showed the highest brainstem asymmetry. There was a significant positive correlation between brainstem asymmetry, the asymmetry of strength and quality of upper limb movement, and a significant negative correlation between brainstem asymmetry and manual ability. INTERPRETATION: In pediatric AIS survivors, brainstem asymmetry can serve as an indirect measure of corticospinal tract integrity. It is significantly correlated with strength, quality of movement, and manual ability.

The Brainfit study: efficacy of cognitive training and exergaming in pediatric cancer survivors - a randomized controlled trial.

BACKGROUND: Cancer survival comes at a price: pediatric cancer survivors bear a high risk for a wide range of cognitive difficulties. Therefore, interventions targeting these difficulties are required. The aim of the present clinical trial is to extend empirical evidence about efficacy of cognitive and physical training in pediatric cancer survivors. It is hypothesized that early cognitive and physical interventions affect the remediation of pediatric cancer survivors in terms of improved executive functions (primary outcome). Additional positive effects of cognitive and physical intervention to other areas such as memory and attention are expected (secondary outcome). Changes in cognitive performance are expected to be associated with structural and functional changes in the brain. METHODS: Overall, 150 pediatric cancer survivors and 50 matched controls will be included in this trial. The cancer survivors will be randomly assigned to either a computerized cognitive training, a physical training (exergaming) or a waiting control group. They will be assessed with neuropsychological tests, tests of sport motor performance and physical fitness before and after 8 weeks of training and again at a 3-months follow-up. Moreover, neuroimaging will be performed at each of the three time points to investigate the training impact on brain structure and function. DISCUSSION: With increasing cancer survival rates, evidence-based interventions are of particular importance. New insights into training-related plasticity in the developing brain will further help to develop tailored rehabilitation programs for pediatric cancer survivors. TRIAL REGISTRATION: KEK BE 196/15; KEK ZH 2015-0397; ICTRP NCT02749877 ; date of registration: 30.11.2016; date of first participant enrolment: .18.01.2017.

Lesion size and long-term cognitive outcome after pediatric stroke: A comparison between two techniques to assess lesion size.

BACKGROUND: There is little consensus on how lesion size impacts long-term cognitive outcome after pediatric arterial ischemic stroke (AIS). This study, therefore, compared two techniques to assessed lesion size in the chronic phase after AIS and determined their measurement agreement in relation to cognitive functions in patients after pediatric stroke. METHODS: Twenty-five patients after pediatric AIS were examined in the chronic phase (>2 years after stroke) in respect to intelligence, memory, executive functions, visuo-motor functions, motor abilities, and disease-specific outcome. Lesion size was measured using the ABC/2 formula and segmentation technique (3D Slicer). Correlation analysis determined the association between volumetry techniques and outcome measures in respect to long-term cognitive outcome. RESULTS: The measurements from the ABC/2 and segmentation technique were strongly correlated (r = 0.878, p < .001) and displayed agreement in particular for small lesions. Lesion size from both techniques was significantly correlated with disease-specific outcome (p < .001) and processing speed (p < .005) after controlling for age at stroke and multiple comparison. CONCLUSION: The two techniques showed convergent validity and were both significantly correlated with long-term outcome after pediatric AIS. Compared to the time-consuming segmentation technique, ABC/2 facilitates clinical and research work as it requires relatively little time and is easy to apply.

How is Cerebral Perfusion Associated with Functional Outcome in Pediatric Cancer Survivors?

Pediatric cancer survivors (PCS) experience functional difficulties and brain alterations. However, little is known about cerebral perfusion and its relationship to functional outcome (cognitive and motor performance) in PCS. We examined cerebral blood flow (CBF) in non-brain tumor PCS and the associations between CBF and age, as well as functional outcome. Forty PCS and 40 age-comparable controls were included. CBF did not differ between PCS and controls. CBF decreased with age only in controls. In PCS, CBF was associated with functional outcome. Our data indicate an altered relationship between age and CBF in survivors, with stronger brain-behavior mechanisms after cancer.

Association of Acute Infarct Topography With Development of Cerebral Palsy and Neurologic Impairment in Neonates With Stroke.

BACKGROUND AND OBJECTIVES: Research investigating neonatal arterial ischemic stroke (NAIS) outcomes have shown that combined cortical and basal ganglia infarction or involvement of the corticospinal tract predict cerebral palsy (CP). The research question was whether voxel-based lesion-symptom mapping (VLSM) on acute MRI can identify brain regions associated with CP and neurodevelopmental impairments in NAIS. METHODS: Newborns were recruited from prospective Australian and Swiss pediatric stroke registries. CP diagnosis was based on clinical examination. Language and cognitive-behavioral impairments were assessed using the Pediatric Stroke Outcome Measure, dichotomized to good (0-0.5) or poor (≥1), at ≥18 months of age. Infarcts were manually segmented using diffusion-weighted imaging, registered to a neonatal-specific brain template. VLSM was conducted using MATLAB SPM12 toolbox. A general linear model was used to correlate lesion masks with motor, language, and cognitive-behavioral outcomes. Voxel-wise t-statistics were calculated, correcting for multiple comparisons using family-wise error (FWE) rate. RESULTS: Eighty-five newborns met the inclusion criteria. Infarct lateralization was left hemisphere (62%), right (8%), and bilateral (30%). At a median age of 2.1 years (interquartile range 1.9-2.6), 33% developed CP and 42% had neurologic impairments. Fifty-four grey and white matter regions correlated with CP (t > 4.33; FWE < 0.05), including primary motor pathway regions, such as the precentral gyrus, and cerebral peduncle, and regions functionally connected to the primary motor pathway, such as the pallidum, and corpus callosum motor segment. No significant correlations were found for language or cognitive-behavioral outcomes. DISCUSSION: CP after NAIS correlates with infarct regions directly involved in motor control and in functionally connected regions. Areas associated with language or cognitive-behavioral impairment are less clear.

Cognitive outcome is related to functional thalamo-cortical connectivity after paediatric stroke.

The thalamus has complex connections with the cortex and is involved in various cognitive processes. Despite increasing interest in the thalamus and the underlying thalamo-cortical interaction, little is known about thalamo-cortical connections after paediatric arterial ischaemic stroke. Therefore, the aim of this study was to investigate thalamo-cortical connections and their association with cognitive performance after arterial ischaemic stroke. Twenty patients in the chronic phase after paediatric arterial ischaemic stroke (≥2 years after diagnosis, diagnosed <16 years; aged 5-23 years, mean: 15.1 years) and 20 healthy controls matched for age and sex were examined in a cross-sectional study design. Cognitive performance (selective attention, inhibition, working memory, and cognitive flexibility) was evaluated using standardized neuropsychological tests. Resting-state functional magnetic resonance imaging was used to examine functional thalamo-cortical connectivity. Lesion masks were integrated in the preprocessing pipeline to ensure that structurally damaged voxels did not influence functional connectivity analyses. Cognitive performance (selective attention, inhibition, and working memory) was significantly reduced in patients compared to controls. Network analyses revealed significantly lower thalamo-cortical connectivity for the motor, auditory, visual, default mode network, salience, left/right executive, and dorsal attention network in patients compared with controls. Interestingly, analyses additionally revealed higher thalamo-cortical connectivity in some subdivisions of the thalamus for the default mode network (medial nuclei), motor (lateral nuclei), dorsal attention (anterior nuclei), and the left executive network (posterior nuclei) in patients compared with controls. Increased and decreased thalamo-cortical connectivity strength within the same networks was, however, found in different thalamic subdivisions. Thus, alterations in thalamo-cortical connectivity strength after paediatric stroke seem to point in both directions, with stronger as well as weaker thalamo-cortical connectivity in patients compared with controls. Multivariate linear regression, with lesion size and age as covariates, revealed significant correlations between cognitive performance (selective attention, inhibition, and working memory) and the strength of thalamo-cortical connectivity in the motor, auditory, visual, default mode network, posterior default mode network, salience, left/right executive, and dorsal attention network after childhood stroke. Our data suggest that the interaction between different sub-nuclei of the thalamus and several cortical networks relates to post-stroke cognition. The variability in cognitive outcomes after paediatric stroke might partly be explained by functional thalamo-cortical connectivity strength.

Relationship between motor abilities and executive functions in patients after pediatric stroke.

Patients after pediatric stroke typically experience varying extent of motor and cognitive impairments. During rehabilitation, these impairments are often treated as separate entities. While there is a notion claiming that motor and cognitive functions are interrelated to some degree in healthy children, a minimal amount of evidence exists regarding this issue in patients after pediatric stroke. The purpose of this study was to investigate the association between motor abilities and executive functions in patients after pediatric arterial ischemic stroke. Twenty-seven patients (6 - 23 years) diagnosed with pediatric arterial ischemic stroke in the chronic phase (≥ 2 years after diagnosis, diagnosed < 16 years) and 49 healthy controls (6 - 26 years) were included in this study. Participants completed six tasks from standardized neuropsychological tests assessing the dimensions of executive functions, namely working memory, inhibition, and shifting. Additionally, we assessed hand strength and upper limb performance with two tasks each. In the patient group, the association between upper limb performance and executive functions was stronger than between hand strength and executive functions. Our results point toward the idea of a close interrelation between upper limb performance and executive functions. Training more complex and cognitively engaging motor abilities involving upper limb performance rather than basic motor abilities such as hand strength during a rehabilitation program may have the power to foster executive function development and vice versa in patients after stroke.

Effect of Age at Pediatric Stroke on Long-term Cognitive Outcome.

BACKGROUND AND OBJECTIVES: To investigate the effect of age at pediatric arterial ischemic stroke on long-term cognitive outcome in order to identify patients particularly at risk for the development of long-term cognitive sequelae. METHODS: This cross-sectional study included patients in the chronic phase of stroke (>2 years after stroke) previously diagnosed with neonatal or childhood arterial ischemic stroke and a control group. Participants with active epilepsy, severe learning difficulties, or behavioral problems hindering the cognitive assessment were excluded. Several cognitive domains, including intelligence, executive functions (working memory, inhibition, and cognitive flexibility), processing speed, memory, letter fluency, and visual-motor skills were assessed with neuropsychological tests. Cognitive long-term outcome was compared across patients after neonatal stroke (stroke between 0 and 28 days of life), early childhood stroke (stroke between 29 days and <6 years), and late childhood stroke (stroke between ≥6 and <16 years). RESULTS: Fifty-two patients after neonatal or childhood arterial ischemic stroke (median age 15.3 years, interquartile range [IQR] 10.6-18.7) and 49 healthy controls (median age 13.6 years, IQR 9.8-17.2) met the inclusion criteria. Cognitive outcome was significantly worse in the pediatric stroke group compared to the control group. A nonlinear effect of age at stroke (irrespective of lesion size and lesion location) was found for cognitive flexibility, processing speed, and verbal learning with early childhood stroke (29 days to <6 years), showing significantly worse cognitive outcome compared to neonatal or late childhood stroke (p < 0.05, false discovery rate-corrected). DISCUSSION: Age at stroke is an important factor for poststroke recovery and modulates long-term cognitive outcome irrespective of lesion size and lesion location. Children after early childhood stroke are at particular risk for long-term alterations in cognitive functions.

Pituitary volume in adolescents with non-suicidal self-injury: Preliminary evidence for alterations in pituitary maturation.

BACKGROUND: Non-suicidal self-injury (NSSI), typically observed in the context of various mental disorders, represents a highly prevalent and serious problem among adolescents. Based on studies linking NSSI with stress, alterations in hypothalamic-pituitary-adrenal (HPA) axis functioning have been suggested to contribute to the development and maintenance of this behavior. While research has mainly focused on cortisol - the main hormonal output of this system - to our knowledge, no study has examined pituitary gland volume (PGV) - an alternative approach of assessing HPA axis functionality that is less state-dependent - in adolescents engaging in NSSI. METHODS: Magnetic Resonance Imaging (MRI) was performed among n = 35 adolescents (aged 12-17 years) fulfilling the diagnostic criteria for NSSI disorder according to DSM-5 and n = 31 age-matched healthy controls; PGV was obtained by manual tracing. To test for group differences - our primary aim - a hierarchical linear regression model was computed, controlling for several potential confounding variables. Since adolescence reflects a time period for significant brain development - including changes in PGV - we also tested for an age-dependent group effect. In a second step, we aimed to investigate whether differences in PGV are accounted for by the experience of childhood adversity or psychopathology. Finally, following an exploratory approach, the dimensional association between PGV and various clinical characteristics (e.g., frequency of NSSI) were explored. RESULTS: No evidence was found for overall volumetric differences between healthy control participants and adolescents engaging in NSSI (p > 0.05) - recognizing that small effect size differences could not be detected in the present study - but group membership significantly interacted with age in predicting PGV (p = 0.02). Particularly, while PGV increased linearly with age in healthy controls (B = 61.39, SE = 14.94, p < 0.01), no corresponding association was found in NSSI patients (B = 16.83, SE = 12.20, p = 0.17). PGV was not related to adverse experiences during childhood and none of the clinical characteristics (e.g., frequency of NSSI) significantly correlated with PGV (p > 0.05). CONCLUSION: These results provide preliminary evidence for alterations in pituitary maturation in adolescents engaging in NSSI, although replication in longitudinal studies with larger samples is warranted.