Trials of endovascular thrombectomy of basilar-artery occlusion compared to real-life data.

BACKGROUND: Two recent clinical trials showed mechanical thrombectomy (MT) of basilar-artery occlusions (BAO) in stroke to be safe and effective: Endovascular Treatment for Acute BAO (ATTENTION) and BAO Chinese Endovascular (BAOCHE). The trials restricted patient inclusion on both age and pre-stroke mRS, and with both trials conducted in China, population differences may affect generalisability of the trial results. METHODS: Consecutive patients with BAO undergoing MT were registered from 2017 to 2021 with retrospective data collection at a single centre with a predominantly Caucasian catchment population of 2.7 million. Age and pre-stroke modified Rankin Scale (mRS) were not absolute contraindications for MT. We present functional outcome as mRS at 90 days, patient characteristics and procedural safety compared to the trial intervention groups. RESULTS: Of the 108 included patients, 50 % achieved mRS 0-3 at 90 days and mortality was 32 %, which was no different from ATTENTION (46 %, p = 0.40, 37 %, p = 0.31, respectively) and BAOCHE (46 %, p = 0.50, 31 %, p = 0.93). Pre-stroke mRS 0 was seen in 62 %, 89 %, and 77 % of the study patients, ATTENTION, and BAOCHE, respectively. Proximal segment BAO was less common (22 % vs. 31 %, p = 0.04, and 65 %, p < 0.01) and intracranial stenting less frequently used (9 % vs. 40 % and 55 %, p < 0.01) in study patients compared to ATTENTION and BAOCHE, respectively. CONCLUSION: Outcome of MT in BAO stroke in a clinical patient cohort was similar to recent trials, despite broader patient inclusion and differences in both occluded BAO segment and use of stenting. Our study suggest that MT is safe and effective in a Caucasian population.

Increased intracranial pressure in acute bacterial meningitis.

Acute bacterial meningitis (ABM) is associated with increased intracranial pressure (ICP) caused by bacterial invasion and the host response to infection. Antibiotic therapy is a sine qua non, and adjunct dexamethasone decreases mortality. The ICP increase may have a rapid course and death due to herniation is most often seen within the first week. Evidence regarding treatment of increased ICP in ABM is limited; this review summarises observational studies which point towards reduced mortality by applying a structured approach towards normalization of ICP in ABM.

Mechanical thrombectomy in ischaemic apoplexy and large vessel occlusion.

In Denmark, approximately 700 patients with ischaemic stroke and large vessel occlusion are treated annually with mechanical thrombectomy (MT). Treatment is proven up to 24 hours if the patients still have salvageable brain tissue and includes patients with occlusions in the anterior and posterior cerebral circulation, and with large volume infarcts. Future studies may expand the treatment indication, as argued in this review. Danish national data on MT have shown that the implementation in daily clinical routine is as effective and safe as reported in the randomized clinical trials.

Endovascular occlusion of a persistent stapedial artery prior to stapedotomy: a novel approach.

BACKGROUND: The stapedial artery is an embryonic artery that transiently supplies the cranial vasculature of the human embryo. Postnatal persistence of the stapedial artery may cause conductive hearing loss and pulsatile tinnitus due to its course through the middle ear. We describe a patient with a persistent stapedial artery (PSA) managed by endovascular coil occlusion prior to stapedotomy. METHODS: A 48-year-old woman presented with left-sided conductive hearing loss and pulsatile tinnitus. Ten years earlier the patient had undergone explorative tympanoplasty, which was aborted due to a large PSA. Digital subtraction angiography was performed to confirm the anatomy and endovascular occlusion of the proximal PSA was achieved by deployment of coils. RESULTS: The pulsatile tinnitus improved immediately after the procedure. The size of the artery subsequently decreased and surgery could be performed with only a minor intraoperative bleeding. Successful stapedotomy resulted in postoperative normalization of her hearing with some minor residual tinnitus. CONCLUSION: Endovascular coil occlusion of a PSA is feasible and safe in patients with favorable anatomy and facilitates middle ear surgery. It decreases the size of the artery and minimizes the risk of intraoperative bleeding in patients with a large PSA. The future role of this novel technique in the management of patients with PSA-related conductive hearing loss and pulsatile tinnitus remains to be determined.

The Positive Predictive Value of Pediatric Stroke Diagnoses in Administrative Data: A Retrospective Validation Study.

Background: This retrospective cohort study aimed to examine the positive predictive value (PPV) of pediatric stroke diagnoses in the Danish National Registry of Patients (DNRP) and the impact of different stroke definitions on the PPV. Methods: We included children registered with a stroke or stroke-related diagnosis in the DNRP between January 2017 through December 2020. Two assessors reviewed medical records and validated cases according to the American Heart and American Stroke Association (AHA/ASA) stroke definition. The level of interrater agreement was examined using kappa statistics. Validation by the AHA/ASA definition was compared with validation according to the definition in the International Classification of Disease 11th version (ICD-11) and the World Health Organization's definition. Results: Stroke was confirmed in 120 of 309 included children, yielding an overall PPV of 0.39 (95% CI: 0.33-0.45). PPV varied across stroke subtypes from 0.83 (95% CI: 0.71-0.92) for ischemic stroke (AIS), 0.57 (95% CI: 0.37-0.76) for unspecified stroke, 0.42 (95% CI: 0.33-0.52) for intracerebral hemorrhage (ICH) to 0.31 (95% CI: 0.55-0.98) and 0.07 (95% CI: 0.01-0.22) for cerebral venous thrombosis and subarachnoid hemorrhage (SAH), respectively. Most non-confirmed ICH and SAH diagnoses were in children with traumatic intracranial hemorrhages (36 and 66% respectively). Among 70 confirmed AIS cases, 25 (36%) were identified in non-AIS code groups. PPV varied significantly across stroke definitions with the highest for the AHA/ASA definition (PPV = 0.39, 95% CI: 0.34-0.45) and the lowest for the WHO definition (PPV = 0.29, 95% CI: 0.24-0.34). Correspondingly, the incidence of pediatric AIS per 100.000 person-years changed from 1.5 for the AHA/ASA definition to 1.2 for ICD-11 and 1.0 for the WHO-definition. The overall interrater agreement was considered excellent (κ=0.85). Conclusion: After validation, stroke was confirmed in only half of the children registered in the DNRP with a stroke-specific diagnosis. Non-validated administrative data should be used with caution in pediatric stroke research. Pediatric stroke incidence rates may vary markedly depending on which stroke definition is used.

Resting-state oscillations reveal disturbed excitation-inhibition ratio in Alzheimer's disease patients.

An early disruption of neuronal excitation-inhibition (E-I) balance in preclinical animal models of Alzheimer's disease (AD) has been frequently reported, but is difficult to measure directly and non-invasively in humans. Here, we examined known and novel neurophysiological measures sensitive to E-I in patients across the AD continuum. Resting-state magnetoencephalography (MEG) data of 86 amyloid-biomarker-confirmed subjects across the AD continuum (17 patients diagnosed with subjective cognitive decline, 18 with mild cognitive impairment (MCI) and 51 with dementia due to probable AD (AD dementia)), 46 healthy elderly and 20 young control subjects were reconstructed to source-space. E-I balance was investigated by detrended fluctuation analysis (DFA), a functional E/I (fE/I) algorithm, and the aperiodic exponent of the power spectrum. We found a disrupted E-I ratio in AD dementia patients specifically, by a lower DFA, and a shift towards higher excitation, by a higher fE/I and a lower aperiodic exponent. Healthy subjects showed lower fE/I ratios (< 1.0) than reported in previous literature, not explained by age or choice of an arbitrary threshold parameter, which warrants caution in interpretation of fE/I results. Correlation analyses showed that a lower DFA (E-I imbalance) and a lower aperiodic exponent (more excitation) was associated with a worse cognitive score in AD dementia patients. In contrast, a higher DFA in the hippocampi of MCI patients was associated with a worse cognitive score. This MEG-study showed E-I imbalance, likely due to increased excitation, in AD dementia, but not in early stage AD patients. To accurately determine the direction of shift in E-I balance, validations of the currently used markers and additional in vivo markers of E-I are required.

Acute triage of childhood stroke in Denmark.

OBJECTIVE: This 2-year observational study aimed to test the feasibility of implementing a pediatric stroke triage-setup that connected frontline providers with vascular neurologists and to examine final diagnoses in children triaged for suspected stroke. METHODS: Prospective, consecutive registration of children with suspected stroke triaged by a team of vascular neurologists from Jan 1st, 2020 and through Dec 2021, Eastern Denmark (census 530,000 children). Based on the provided clinical information, the children were triaged to either assessment at the Comprehensive Stroke Center (CSC) in Copenhagen or to a pediatric department. All included children were retrospectively followed-up for clinical presentations and final diagnosis. RESULTS: A total of 163 children with 166 suspected stroke events were triaged by the vascular neurologists. Cerebrovascular disease was present in 15 (9.0%) suspected stroke events; one child had intracerebral hemorrhage, one had subarachnoid hemorrhage, two children presented with three TIA events and nine children presented with 10 ischemic stroke events. Two children with ischemic stroke were eligible for acute revascularization treatment of which both were triaged to the CSC. The sensitivity of the triage by acute revascularization indication was 1.00 (95% confidence interval (95% CI): 0.15-1.00) and specificity 0.65 (95% CI: 0.57-0.73). Non-stroke neurological emergencies were present in 34 (20.5%) children, including seizures in 18 (10.8%) and acute demyelinating disorders in 7 (4.2%). CONCLUSION: Implementing regional triage-setup that connected frontline providers to vascular neurologists was feasible; this system was activated for the majority of children with ischemic stroke according to an expected incidence and led to identification of children eligible for revascularization treatments.

The impact of SWI/SNF and NuRD inactivation on gene expression is tightly coupled with levels of RNA polymerase II occupancy at promoters.

SWI/SNF and NuRD are protein complexes that antagonistically regulate DNA accessibility. However, repression of their activities often leads to unanticipated changes in target gene expression (paradoxical), highlighting our incomplete understanding of their activities. Here we show that SWI/SNF and NuRD are in a tug-of-war to regulate PRC2 occupancy at lowly expressed and bivalent genes in mouse embryonic stem cells (mESCs). In contrast, at promoters of average or highly expressed genes, SWI/SNF and NuRD antagonistically modulate RNA polymerase II (Pol II) release kinetics, arguably owing to accompanying alterations in H3.3 and H2A.Z levels at promoter-flanking nucleosomes, leading to paradoxical changes in gene expression. Owing to this mechanism, the relative activities of the two remodelers potentiate gene promoters toward Pol II-dependent open or PRC2-dependent closed chromatin states. Our results highlight RNA Pol II occupancy as the key parameter in determining the direction of gene expression changes in response to SWI/SNF and NuRD inactivation at gene promoters in mESCs.

Prediction of Behavioral Improvement Through Resting-State Electroencephalography and Clinical Severity in a Randomized Controlled Trial Testing Bumetanide in Autism Spectrum Disorder.

BACKGROUND: Mechanism-based treatments such as bumetanide are being repurposed for autism spectrum disorder. We recently reported beneficial effects on repetitive behavioral symptoms that might be related to regulating excitation-inhibition (E/I) balance in the brain. Here, we tested the neurophysiological effects of bumetanide and the relationship to clinical outcome variability and investigated the potential for machine learning-based predictions of meaningful clinical improvement. METHODS: Using modified linear mixed models applied to intention-to-treat population, we analyzed E/I-sensitive electroencephalography (EEG) measures before and after 91 days of treatment in the double-blind, randomized, placebo-controlled Bumetanide in Autism Medication and Biomarker study. Resting-state EEG of 82 subjects out of 92 participants (7-15 years) were available. Alpha frequency band absolute and relative power, central frequency, long-range temporal correlations, and functional E/I ratio treatment effects were related to the Repetitive Behavior Scale-Revised (RBS-R) and the Social Responsiveness Scale 2 as clinical outcomes. RESULTS: We observed superior bumetanide effects on EEG, reflected in increased absolute and relative alpha power and functional E/I ratio and in decreased central frequency. Associations between EEG and clinical outcome change were restricted to subgroups with medium to high RBS-R improvement. Using machine learning, medium and high RBS-R improvement could be predicted by baseline RBS-R score and EEG measures with 80% and 92% accuracy, respectively. CONCLUSIONS: Bumetanide exerts neurophysiological effects related to clinical changes in more responsive subsets, in whom prediction of improvement was feasible through EEG and clinical measures.

Mechanical thrombectomy in stroke patients of advanced age with score-based prediction of outcome.

BACKGROUND: Stroke patients ≥80 years constituted only 15% in randomised trials on mechanical thrombectomy (MT), but is a considerable higher proportion in clinical practice. Association of clinical variables collected before MT with functional outcome has not been independently described in these patients, while being important in the decision of patient eligibility for MT. METHODS: We included patients consecutively at a single centre (2017-2021) categorised as octogenarians (age: 80-89 years) or nonagenarians (age: 90-99 years). Functional outcome at 90 days was defined as fair (modified Rankin Scale (mRS) 0-3) or poor (mRS 4-6). Clinical variables collected before MT were analysed for association with shift of mRS in a poor direction. Significant predictors were used to produce a risk score of fair outcome. Significance was set at the p < 0.05 level. RESULTS: Nonagenarians (n = 43, 15.5%) compared to octogenarians (n = 235, 84.5%) less likely achieved fair outcome (20.9% vs. 46.0%, p < 0.01) with higher mortality (65.1% vs. 31.9%, p < 0.01). Significant predictors of outcome were: age, adjusted odds ratio (aOR) = 0.91 (95% confidence interval (CI): 0.86-0.97); pre-stroke mRS, aOR = 0.57 (95% CI: 0.44-0.73); National Institute of Health Stroke Scale at admission, aOR = 0.91 (95% CI: 0.87-0.95); Alberta Stroke Program Early Computed Tomography, aOR = 1.23 (95% CI: 1.05-1.45). After bootstrap validation, the area under the curve of the risk score was 0.74 and the optimal cut-off for fair outcome was a score of >7 points. CONCLUSIONS: One in two octogenarians achieved fair outcome, however, only one in five nonagenarians had fair outcome. The clinical risk score could be considered as guidance when deciding patient eligibility for MT.

Predictive Value of Pediatric Stroke Diagnoses in Administrative Data: A Systematic Literature Review.

BACKGROUND AND AIM: Administrative healthcare data are frequently used for studying incidence, prevalence, risk factors, and outcome of pediatric stroke. However, the accuracy of these data sources is uncertain. The aim of this study was to systematically analyze published data on the positive predictive value (PPV) and sensitivity of diagnoses used to identify pediatric stroke patients in administrative data. METHODS: This systematic review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We searched PubMed and Embase for studies, published in year 2000 or later, describing the PPV or sensitivity of diagnoses used to identify children with stroke in administrative data. The search was performed on June 9, 2022. Studies written in other languages than English, with less than 30 participants, and conference abstracts were excluded. RESULTS: Eight studies were included after full-text review from 2,475 potentially eligible records. These included 3,137 children. All studies reported data from high-income countries. Reported PPVs varied considerably across studies and stroke subtypes: acute ischemic stroke, range 0.27-0.89; cerebral venous thrombosis, range 0.45-0.72; spontaneous subarachnoid hemorrhage, range 0.52-0.83; and spontaneous intracerebral hemorrhage, range 0.62-0.66. One study examined sensitivity of an ICD-9 search compared to a radiology report search and found that the ICD search had poor sensitivity (33%). CONCLUSION: Caution is recommended in the use and interpretation of nonvalidated administrative data for pediatric stroke. Data on the PPV and sensitivity of pediatric stroke diagnoses in administrative data remain limited and are only available from high-income countries.

Intellectually able adults with autism spectrum disorder show typical resting-state EEG activity.

There is broad interest in discovering quantifiable physiological biomarkers for psychiatric disorders to aid diagnostic assessment. However, finding biomarkers for autism spectrum disorder (ASD) has proven particularly difficult, partly due to high heterogeneity. Here, we recorded five minutes eyes-closed rest electroencephalography (EEG) from 186 adults (51% with ASD and 49% without ASD) and investigated the potential of EEG biomarkers to classify ASD using three conventional machine learning models with two-layer cross-validation. Comprehensive characterization of spectral, temporal and spatial dimensions of source-modelled EEG resulted in 3443 biomarkers per recording. We found no significant group-mean or group-variance differences for any of the EEG features. Interestingly, we obtained validation accuracies above 80%; however, the best machine learning model merely distinguished ASD from the non-autistic comparison group with a mean balanced test accuracy of 56% on the entirely unseen test set. The large drop in model performance between validation and testing, stress the importance of rigorous model evaluation, and further highlights the high heterogeneity in ASD. Overall, the lack of significant differences and weak classification indicates that, at the group level, intellectually able adults with ASD show remarkably typical resting-state EEG.

Reducing delay to endovascular reperfusion after relocating a thrombolysis unit.

Background and aims: Functional outcome following mechanical thrombectomy (MT) in patients with acute ischemic stroke and large vessel occlusion is time-dependent and worsens with increasing delay. Time to endovascular reperfusion is potentially modifiable with changes in organizational structure. We investigated the changes in time to reperfusion of relocating the intravenous thrombolysis (IVT) services from a non-MT center to a MT-capable center. Methods: We present an observational, consecutive, retrospective, single-center cohort study of 253 stroke patients treated with MT, 2017-2019. The observation period was divided into before and after the relocation of IVT services in 2018, period 1 and period 2, respectively. The two hospitals were located 13 km apart in an urban area, and following the relocation, IVT was administered at the MT-capable center. Time metrics were registered and divided into two main intervals, namely, ambulance departure from stroke onset location to imaging (ambulance-imaging) and imaging to reperfusion (imaging-reperfusion). The interval imaging-reperfusion included inter-hospital transfer to the MT-capable center in period 1. The association of the imaging-reperfusion duration and functional outcome at 90 days was analyzed using ordinal logistic regression. Results: No significant change in ambulance-imaging was observed from a median of 27 min (interquartile range [IQR] 22-37) in period 1 to 30 min (IQR 23-40) in period 2, p = 0.19, while the median time of imaging-reperfusion decreased from 173 min (IQR 137-230) to 114 min (IQR 84-152), p < 0.001. The largest absolute time reduction from imaging to reperfusion was seen from imaging to arrival at the angio suite from 89 min (IQR 76-111) to 42 min (IQR 28-63), p < 0.001, which included inter-hospital transfer in period 1. In multivariate analysis, every 10 min of increased delay from imaging to reperfusion was associated with poorer functional outcome with an adjusted odds ratio of 0.95 (95% CI: 0.95-0.98), p < 0.001. Conclusion: Relocation of IVT services to an MT-capable center was the main cause of reduced time to reperfusion for patients treated with MT and was implemented without affecting prehospital transportation time. These results suggest that patient outcome can be improved by optimizing the organization of IVT and MT services in urban areas.

Hemorrhage due to a pseudoaneurysm on a dural-pial anastomosis after decompression for Chiari malformation type I: case report.

While intracranial aneurysms rarely develop after neurosurgical procedures, delayed pseudoaneurysm formation after foramen magnum decompression (FMD) has never been reported. A 52-year-old woman presented with an atypical subarachnoid hemorrhage in the posterior fossa 12 years after a FMD for symptomatic Chiari malformation type I was performed. A pseudoaneurysm on a dural-pial anastomosis was identified as the bleeding source and successfully occluded by endovascular means with full clinical recovery of the patient. Injury to the distal posterior inferior cerebellar artery related to surgery and postoperative infection likely caused formation of a dural-pial anastomosis. Additionally, hemodynamic stress or dissection may have contributed to delayed pseudoaneurysm formation and rupture.

Improved Manual Annotation of EEG Signals through Convolutional Neural Network Guidance.

The development of validated algorithms for automated handling of artifacts is essential for reliable and fast processing of EEG signals. Recently, there have been methodological advances in designing machine-learning algorithms to improve artifact detection of trained professionals who usually meticulously inspect and manually annotate EEG signals. However, validation of these methods is hindered by the lack of a gold standard as data are mostly private and data annotation is time consuming and error prone. In the effort to circumvent these issues, we propose an iterative learning model to speed up and reduce errors of manual annotation of EEG. We use a convolutional neural network (CNN) to train on expert-annotated eyes-open and eyes-closed resting-state EEG data from typically developing children (n = 30) and children with neurodevelopmental disorders (n = 141). To overcome the circular reasoning of aiming to develop a new algorithm and benchmarking to a manually-annotated gold standard, we instead aim to improve the gold standard by revising the portion of the data that was incorrectly learned by the network. When blindly presented with the selected signals for re-assessment (23% of the data), the two independent expert-annotators changed the annotation in 25% of the cases. Subsequently, the network was trained on the expert-revised gold standard, which resulted in improved separation between artifacts and nonartifacts as well as an increase in balanced accuracy from 74% to 80% and precision from 59% to 76%. These results show that CNNs are promising to enhance manual annotation of EEG artifacts and can be improved further with better gold-standard data.

[A rare caseof anarthriaand dysphagia].

Sudden onset anarthria and dysphagia without lateralised neurologic symptoms should prompt an investigation for pseudobulbar palsy, either due to bilateral vascular lesions of the corticobulbar tracts or, less frequently, Foix-Chavany-Marie Syndrome (FCMS). Here, bilateral damage to the frontal opercular cortex leads to loss of voluntary control of muscles supplied by cranial nerves V, VII, IX, X, XI, and XII. This case report presents a rare case of FCMS on the background of traumatic cerebral lesions following a bicycle incident.

Acute posterior multifocal placoid pigment epitheliopathy resembling multiple sclerosis.

A 23-year-old man presented with right eye blurred vision; he was diagnosed with acute posterior multifocal placoid pigment epitheliopathy (APMPPE), and his symptoms resolved with prednisolone. Two months later, he developed a right arm weakness that resolved after 3 weeks. MR scan of brain identified changes suggesting multiple sclerosis, with four hyperintense FLAIR lesions; there was contrast enhancement of two lesions and no diffusion restriction. Cerebrospinal fluid showed mononuclear pleocytosis. We eventually diagnosed these as APMPPE-associated CNS lesions. APMPPE is a rare inflammatory chorioretinopathy that rarely can resemble multiple sclerosis clinically and radiologically.

A Unique Constellation of Multiple Cranial Neuropathies in a Patient with Preeclampsia.

A 36-year-old nullipara at 35 weeks of gestation woke up with slurred speech and dysphagia. The next day, she developed abruption of the placenta, underwent an acute cesarean, and was diagnosed with severe preeclampsia. Neurologic examination revealed flaccid dysarthria, bilateral soft palate palsy, reduced taste of the left posterior tongue, left-sided tongue deviation, and paralysis of the left sternocleidomastoid and trapezius muscles. MRI revealed left-sided tongue edema compatible with acute left hypoglossal nerve denervation and electromyography of the left trapezius and glossal muscles showed profuse denervation potentials. In conclusion, multiple cranial neuropathies may occur in and even be a presenting symptom of preeclampsia. In this study, we report the first case of multiple cranial neuropathies involving cranial nerves IX, X, XI, and XII in a patient with preeclampsia. Possible pathogenic mechanisms of cranial neuropathy in preeclampsia include immune-mediated neuropathy with or without demyelination, microvascular thromboses, and perineural edema.

Bumetanide Effects on Resting-State EEG in Tuberous Sclerosis Complex in Relation to Clinical Outcome: An Open-Label Study.

Neuronal excitation-inhibition (E/I) imbalances are considered an important pathophysiological mechanism in neurodevelopmental disorders. Preclinical studies on tuberous sclerosis complex (TSC), suggest that altered chloride homeostasis may impair GABAergic inhibition and thereby E/I-balance regulation. Correction of chloride homeostasis may thus constitute a treatment target to alleviate behavioral symptoms. Recently, we showed that bumetanide-a chloride-regulating agent-improved behavioral symptoms in the open-label study Bumetanide to Ameliorate Tuberous Sclerosis Complex Hyperexcitable Behaviors trial (BATSCH trial; Eudra-CT: 2016-002408-13). Here, we present resting-state EEG as secondary analysis of BATSCH to investigate associations between EEG measures sensitive to network-level changes in E/I balance and clinical response to bumetanide. EEGs of 10 participants with TSC (aged 8-21 years) were available. Spectral power, long-range temporal correlations (LRTC), and functional E/I ratio (fE/I) in the alpha-frequency band were compared before and after 91 days of treatment. Pre-treatment measures were compared against 29 typically developing children (TDC). EEG measures were correlated with the Aberrant Behavioral Checklist-Irritability subscale (ABC-I), the Social Responsiveness Scale-2 (SRS-2), and the Repetitive Behavior Scale-Revised (RBS-R). At baseline, TSC showed lower alpha-band absolute power and fE/I than TDC. Absolute power increased through bumetanide treatment, which showed a moderate, albeit non-significant, correlation with improvement in RBS-R. Interestingly, correlations between baseline EEG measures and clinical outcomes suggest that most responsiveness might be expected in children with network characteristics around the E/I balance point. In sum, E/I imbalances pointing toward an inhibition-dominated network are present in TSC. We established neurophysiological effects of bumetanide although with an inconclusive relationship with clinical improvement. Nonetheless, our results further indicate that baseline network characteristics might influence treatment response. These findings highlight the possible utility of E/I-sensitive EEG measures to accompany new treatment interventions for TSC. Clinical Trial Registration: EU Clinical Trial Register, EudraCT 2016-002408-13 (www.clinicaltrialsregister.eu/ctr-search/trial/2016-002408-13/NL). Registered 25 July 2016.