Safety and clinical outcomes of endovascular therapy versus medical management in late presentation of large ischemic stroke.

INTRODUCTION: The benefit of endovascular therapy (EVT) among stroke patients with large ischemic core (ASPECTS 0-5) in the extended time window outside of trial settings remains unclear. We analyzed the effect of EVT among these stroke patients in real-world settings. PATIENTS AND METHODS: The CT for Late Endovascular Reperfusion (CLEAR) study recruited patients from 66 centers in 10 countries between 01/2014 and 05/2022. The extended time-window was defined as 6-24 h from last-seen-well to treatment. The primary outcome was shift of the 3-month modified Rankin scale (mRS) score. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and mortality. Outcomes were analyzed with ordinal and logistic regressions. RESULTS: Among 5098 screened patients, 2451 were included in the analysis (median age 73, 55% women). Of patients with ASPECTS 0-5 (n = 310), receiving EVT (n = 209/310) was associated with lower 3-month mRS when compared to medical management (median 4 IQR 3-6 vs 6 IQR 4-6; aOR 0.4, 95% CI 0.2-0.7). Patients undergoing EVT had higher sICH (11.2% vs 4.0%; aOR 4.1, 95% CI 1.2-18.8) and lower mortality (31.6% vs 58.4%, aOR 0.4; 95% CI 0.2-0.9) compared to medically managed patients. The relative benefit of EVT was comparable between patients with ASPECTS 0 and 5 and 6-10 in the extended time window (interaction aOR 0.9; 95% CI 0.5-1.7). CONCLUSION: In the extended time window, patients with ASPECTS 0-5 may have preserved relative treatment benefit of EVT compared to patients with ASPECTS 6-10. These findings are in line with recent trials showing benefit of EVT among real-world patients with large ischemic core in the extended time window. TRIAL REGISTRATION NUMBER: clinicaltrials.gov; Unique identifier: NCT04096248.

Incidence, Risk Factors and Clinical Implications of Subarachnoid Hyperdensities on Flat-Panel Detector Computed Tomography following Mechanical Thrombectomy in Anterior Circulation Acute Ischemic Stroke Patients.

BACKGROUND AND PURPOSE: Flat-panel detector computed tomography (FDCT) immediately after mechanical thrombectomy (MT) can detect complications including early hemorrhagic transformation and subarachnoid hyperdensities (SH). The clinical significance of SH in patients undergoing MT remains unclear. MATERIALS AND METHODS: We studied 223 patients who underwent MT for anterior circulation stroke, had FDCT performed immediately after the procedure, and had follow-up imaging within 24 hours. SH severity was categorized into 5 grades (SH 0: absent to SH IV: extensive). Baseline and procedural characteristics, as well as outcome measures, were analyzed using group comparisons and multivariable logistic regression analyses. RESULTS: Overall, 100/223 (45%) of patients showed SH on immediate post-interventional FDCT. The factors associated with an increased SH risk were: medium vessel occlusion or distal vessel occlusion as compared to a large vessel occlusion, a more distal device position, a higher number of device passes, a larger volume of contrast applied, and worse final reperfusion eTICI. Occurrence of SH grade II-IV was independently associated with worse functional outcomes (aOR for mRS 3-6: 2.2, 95% CI 1.1-4.3), whereas patients with SH grade I had similar outcomes to patients without SH. CONCLUSIONS: Our study identified risk factors for SH, most of which reflect increasingly challenging procedures or more peripheral recanalization attempts. The presence of SH grades II-IV was associated with poorer outcomes, suggesting the need for personalized strategies to reduce its incidence and severity or potentially improve recovery after SH. ABBREVIATIONS: DVO = distal vessel occlusion; FDCT = flat-panel detector computed tomography; LVO = large vessel occlusion; MVO = medium vessel occlusion; MT = mechanical thrombectomy; SH = subarachnoid hyperdensities.

Flat-panel Detector Perfusion Imaging and Conventional Multidetector Perfusion Imaging in Patients with Acute Ischemic Stroke : A Comparative Study.

PURPOSE: Flat-panel detector computed tomography (FDCT) is increasingly used in (neuro)interventional angiography suites. This study aimed to compare FDCT perfusion (FDCTP) with conventional multidetector computed tomography perfusion (MDCTP) in patients with acute ischemic stroke. METHODS: In this study, 19 patients with large vessel occlusion in the anterior circulation who had undergone mechanical thrombectomy, baseline MDCTP and pre-interventional FDCTP were included. Hypoperfused tissue volumes were manually segmented on time to maximum (Tmax) and time to peak (TTP) maps based on the maximum visible extent. Absolute and relative thresholds were applied to the maximum visible extent on Tmax and relative cerebral blood flow (rCBF) maps to delineate penumbra volumes and volumes with a high likelihood of irreversible infarcted tissue ("core"). Standard comparative metrics were used to evaluate the performance of FDCTP. RESULTS: Strong correlations and robust agreement were found between manually segmented volumes on MDCTP and FDCTP Tmax maps (r = 0.85, 95% CI 0.65-0.94, p < 0.001; ICC = 0.85, 95% CI 0.69-0.94) and TTP maps (r = 0.91, 95% CI 0.78-0.97, p < 0.001; ICC = 0.90, 95% CI 0.78-0.96); however, direct quantitative comparisons using thresholding showed lower correlations and weaker agreement (MDCTP versus FDCTP Tmax 6 s: r = 0.35, 95% CI -0.13-0.69, p = 0.15; ICC = 0.32, 95% CI 0.07-0.75). Normalization techniques improved results for Tmax maps (r = 0.78, 95% CI 0.50-0.91, p < 0.001; ICC = 0.77, 95% CI 0.55-0.91). Bland-Altman analyses indicated a slight systematic underestimation of FDCTP Tmax maximum visible extent volumes and slight overestimation of FDCTP TTP maximum visible extent volumes compared to MDCTP. CONCLUSION: FDCTP and MDCTP provide qualitatively comparable volumetric results on Tmax and TTP maps; however, direct quantitative measurements of infarct core and hypoperfused tissue volumes showed lower correlations and agreement.

Connecting the DOTs: a novel imaging sign on flat-panel detector CT indicating distal vessel occlusions after thrombectomy.

BACKGROUND: Immediate non-contrast post-interventional flat-panel detector CT (FPDCT) has been suggested as an imaging tool to assess complications after endovascular therapy (EVT). We systematically investigated a new imaging finding of focal hyperdensities correlating with remaining distal vessel occlusion after EVT. METHODS: A single-center retrospective analysis was conducted for all acute ischemic stroke patients admitted between July 2020 and December 2022 who underwent EVT and immediate post-interventional FPDCT. A blinded core lab performed reperfusion grading on post-interventional digital subtraction angiography (DSA) images and evaluated focal hyperdensities on FPDCT (here called the distal occlusion tracker (DOT) sign). DOT sign was defined as a tubular or punctiform, vessel confined, hyperdense signal within the initial occlusion target territory. We assessed sensitivity and specificity of the DOT sign when compared with DSA findings. RESULTS: The median age of the cohort (n=215) was 74 years (IQR 63-82) and 58.6% were male. The DOT sign was positive in half of the cohort (51%, 110/215). The DOT sign had high specificity (85%, 95% CI 72% to 93%), but only moderate sensitivity (63%, 95% CI 55% to 70%) for detection of residual vessel occlusions. In comparison to the core lab, operators overestimated complete reperfusion in a quarter of the entire cohort (25%, 53/215). In more than half of these cases (53%, 28/53) there was a positive DOT sign, which could have mitigated this overestimation. CONCLUSION: The DOT sign appears to be a frequent finding on immediate post-interventional FPDCT. It correlates strongly with incomplete reperfusion and indicates residual distal vessel occlusions. In the future, it may be used to complement grading of reperfusion success and may help mitigating overestimation of reperfusion in the acute setting.

Value of Immediate Flat Panel Perfusion Imaging after Endovascular Therapy (AFTERMATH): A Proof of Concept Study.

BACKGROUND AND PURPOSE: Potential utility of flat panel CT perfusion imaging (FPCT-PI) performed immediately after mechanical thrombectomy (MT) is unknown. We aimed to assess whether FPCT-PI obtained directly post-MT could provide additional potentially relevant information on tissue reperfusion status. MATERIALS AND METHODS: This was a single-center analysis of all patients with consecutive acute stroke admitted between June 2019 and March 2021 who underwent MT and postinterventional FPCT-PI (n = 26). A core lab blinded to technical details and clinical data performed TICI grading on postinterventional DSA images and qualitatively assessed reperfusion on time-sensitive FPCT-PI maps. According to agreement between DSA and FPCT-PI, all patients were classified into 4 groups: hypoperfusion findings perfectly matched by location (group 1), hypoperfusion findings mismatched by location (group 2), complete reperfusion on DSA with hypoperfusion on FPCT-PI (group 3), and hypoperfusion on DSA with complete reperfusion on FPCT-PI (group 4). RESULTS: Detection of hypoperfusion (present/absent) concurred in 21/26 patients. Of these, reperfusion findings showed perfect agreement on location and size in 16 patients (group 1), while in 5 patients there was a mismatch by location (group 2). Of the remaining 5 patients with disagreement regarding the presence or absence of hypoperfusion, 3 were classified into group 3 and 2 into group 4. FPCT-PI findings could have avoided TICI overestimation in all false-positive operator-rated TICI 3 cases (10/26). CONCLUSIONS: FPCT-PI may provide additional clinically relevant information in a considerable proportion of patients undergoing MT. Hence, FPCT-PI may complement the evaluation of reperfusion efficacy and potentially inform decision-making in the angiography suite.

Neuroanatomical Disposition, Natural Development, and Training-Induced Plasticity of the Human Auditory System from Childhood to Adulthood: A 12-Year Study in Musicians and Nonmusicians.

Auditory perception is fundamental to human development and communication. However, no long-term studies have been performed on the plasticity of the auditory system as a function of musical training from childhood to adulthood. The long-term interplay between developmental and training-induced neuroplasticity of auditory processing is still unknown. We present results from AMseL (Audio and Neuroplasticity of Musical Learning), the first longitudinal study on the development of the human auditory system from primary school age until late adolescence. This 12-year project combined neurologic and behavioral methods including structural magnetic resonance imaging (MRI), magnetoencephalography (MEG), and auditory tests. A cohort of 112 typically developing participants (51 male, 61 female), classified as "musicians" (n = 66) and "nonmusicians" (n = 46), was tested at five measurement timepoints. We found substantial, stable differences in the morphology of auditory cortex (AC) between musicians and nonmusicians even at the earliest ages, suggesting that musical aptitude is manifested in macroscopic neuroanatomical characteristics. Maturational plasticity led to a continuous increase in white matter myelination and systematic changes of the auditory evoked P1-N1-P2 complex (decreasing latencies, synchronization effects between hemispheres, and amplitude changes) regardless of musical expertise. Musicians showed substantial training-related changes at the neurofunctional level, in particular more synchronized P1 responses and bilaterally larger P2 amplitudes. Musical training had a positive influence on elementary auditory perception (frequency, tone duration, onset ramp) and pattern recognition (rhythm, subjective pitch). The observed interplay between "nature" (stable biological dispositions and natural maturation) and "nurture" (learning-induced plasticity) is integrated into a novel neurodevelopmental model of the human auditory system.Significance Statement We present results from AMseL (Audio and Neuroplasticity of Musical Learning), a 12-year longitudinal study on the development of the human auditory system from childhood to adulthood that combined structural magnetic resonance imaging (MRI), magnetoencephalography (MEG), and auditory discrimination and pattern recognition tests. A total of 66 musicians and 46 nonmusicians were tested at five timepoints. Substantial, stable differences in the morphology of auditory cortex (AC) were found between the two groups even at the earliest ages, suggesting that musical aptitude is manifested in macroscopic neuroanatomical characteristics. We also observed neuroplastic and perceptual changes with age and musical practice. This interplay between "nature" (stable biological dispositions and natural maturation) and "nurture" (learning-induced plasticity) is integrated into a novel neurodevelopmental model of the human auditory system.

Examining Individual Differences in Singing, Musical and Tone Language Ability in Adolescents and Young Adults with Dyslexia.

In recent years, evidence has been provided that individuals with dyslexia show alterations in the anatomy and function of the auditory cortex. Dyslexia is considered to be a learning disability that affects the development of music and language capacity. We set out to test adolescents and young adults with dyslexia and controls (N = 52) for their neurophysiological differences by investigating the auditory evoked P1-N1-P2 complex. In addition, we assessed their ability in Mandarin, in singing, their musical talent and their individual differences in elementary auditory skills. A discriminant analysis of magnetencephalography (MEG) revealed that individuals with dyslexia showed prolonged latencies in P1, N1, and P2 responses. A correlational analysis between MEG and behavioral variables revealed that Mandarin syllable tone recognition, singing ability and musical aptitude (AMMA) correlated with P1, N1, and P2 latencies, respectively, while Mandarin pronunciation was only associated with N1 latency. The main findings of this study indicate that the earlier P1, N1, and P2 latencies, the better is the singing, the musical aptitude, and the ability to link Mandarin syllable tones to their corresponding syllables. We suggest that this study provides additional evidence that dyslexia can be understood as an auditory and sensory processing deficit.

Neuroimaging in cerebellar ataxia in childhood: A review.

Ataxia is one of the most common pediatric movement disorders and can be caused by a large number of congenital and acquired diseases affecting the cerebellum or the vestibular or sensory system. It is mainly characterized by gait abnormalities, dysmetria, intention tremor, dysdiadochokinesia, dysarthria, and nystagmus. In young children, ataxia may manifest as the inability or refusal to walk. The diagnostic approach begins with a careful clinical history including the temporal evolution of ataxia and the inquiry of additional symptoms, is followed by a meticulous physical examination, and, depending on the results, is complemented by laboratory assays, electroencephalography, nerve conduction velocity, lumbar puncture, toxicology screening, genetic testing, and neuroimaging. Neuroimaging plays a pivotal role in either providing the final diagnosis, narrowing the differential diagnosis, or planning targeted further workup. In this review, we will focus on the most common form of ataxia in childhood, cerebellar ataxia (CA). We will discuss and summarize the neuroimaging findings of either the most common or the most important causes of CA in childhood or present causes of pediatric CA with pathognomonic findings on MRI. The various pediatric CAs will be categorized and presented according to (a) the cause of ataxia (acquired/disruptive vs. inherited/genetic) and (b) the temporal evolution of symptoms (acute/subacute, chronic, progressive, nonprogressive, and recurrent). In addition, several illustrative cases with their key imaging findings will be presented.

Neuromorphological and Neurofunctional Correlates of ADHD and ADD in the Auditory Cortex of Adults.

Attention deficit (hyperactivity) disorder (AD(H)D) is one of the most common neurodevelopmental disorders in children with up to 60% probability of prevailing into adulthood. AD(H)D has far-fetching negative impacts on various areas of life. Until today, no observer-independent diagnostic biomarker is available for AD(H)D, however recent research found evidence that AD(H)D is reflected in auditory dysfunctions. Furthermore, the official diagnostic classification systems, being mainly the ICD-10 in Europe and the DSM-5 in the United States, are not entirely consistent. The neuro-auditory profiles of 82 adults (27 ADHD, 30 ADD, 25 controls) were measured via structural magnetic resonance imaging (MRI) and magnetoencephalography (MEG) to determine gray matter volumes and activity of auditory subareas [Heschl's gyrus (HG) and planum temporale (PT)]. All three groups (ADHD, ADD, and controls) revealed distinct neuro-auditory profiles. In the left hemisphere, both ADHD and ADD showed reduced gray matter volumes of the left HG, resulting in diminished left HG/PT ratios. In the right hemisphere, subjects with ADHD were characterized by lower right HG/PT ratios and ADD by a similar right HG/PT ratio compared to controls. Controls and ADD had well-balanced hemispheric response patterns, ADHD a left-right asynchrony. With this study, we present the structural and functional differences in the auditory cortex of adult patients with AD(H)D.

Duplication of the Pituitary Gland: CT, MRI and DTI Findings and Updated Review of the Literature.

Duplication of the pituitary gland (DPG) is an extremely rare malformation. DPG is associated with a wide variety of midline and central nervous system malformations (DPG-plus syndrome). We present the computed tomography (CT), magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) findings of a rare case of DPG with associated tuberomammillary fusion resulting in a hypothalamic mass-like configuration, oropharyngeal teratoma, cleft palate, hypertelorism, duplicated/broad sella, duplication/low bifurcation of the basilar artery, and craniovertebral midline anomalies. Qualitative interpretation of DTI yielded normal white matter organization of the brain. The duplication of the prechordal plate and the rostral end of the notochordal plate/notochord is thought to be the main factor leading to a duplication of the pituitary primordium and resulting in the formation of two morphologically normal glands. The time of induction of the teratogenic influence, the extent of the prechordal plate and notochordal plate/notochord abnormalities, and the faulty interactions are believed to be the reason for the wide spectrum of associated midline abnormalities.

Lower skeletal muscle mass on CT body composition analysis is associated with adverse clinical course and outcome in children with COVID-19.

OBJECTIVES: To assess the association between body composition measures in children with COVID-19 and severity of the disease course and clinical outcome. METHODS: A retrospective study of children (< 19 years) with COVID-19 admitted to the hospital who underwent CT of the chest and/or abdomen was conducted. Data compiled from electronic medical records included demographics, body mass index (BMI), length of stay, ICU admission, invasive mechanical ventilation and death. Waist circumference and perimeters for skeletal muscle mass (abdominal, psoas and paraspinal muscles) were measured on an axial CT image at the level of the twelfth thoracic vertebra or first lumbar vertebra using FIJI software. RESULTS: Fifty-seven subjects were identified (54% male, median age 15.6 years, 61% Hispanic, 23% African-American). 25% (14/57) were admitted to the ICU and 21% (12/57) needed intubation. 9% (5/57) died. Waist circumference ranged between 53.2 and 138.4 cm (mean 86.58 ± 18.74 cm) and skeletal muscle mass ranged between 0.6 and 6.8 cm2 (mean 3.5 ± 1.19 cm2). Lower skeletal muscle mass had a univariate association with ICU admission (odds ratio (OR) 0.4; 95%CI 0.17-0.76; p = 0.01) and mortality (OR 0.22; 95%CI 0.04-0.69; p = 0.01). Multivariate analysis showed similar association after controlling for comorbidities (adjusted OR 0.46; 95%CI 0.19-0.95; p = 0.04 and adjusted OR 0.31; 95%CI 0.06-0.95; p = 0.04, respectively). There was no association between BMI or waist circumference with ICU stay, mechanical ventilation or mortality. CONCLUSION: Lower skeletal muscle mass is associated with an adverse clinical course and outcome in children with COVID-19.

Neuroimaging of primary mitochondrial disorders in children: A review.

Mitochondrial disorders represent a diverse and complex group of entities typified by defective energy metabolism. The mitochondrial oxidative phosphorylation system is typically impaired, which is the predominant source of energy production. Because mitochondria are present in nearly all organs, multiple systems may be affected including the central nervous system, skeletal muscles, kidneys, and liver. In particular, those organs that are metabolically active with high energy demands are explicitly vulnerable. Initial diagnostic work up relies on a detailed evaluation of clinical symptoms including physical examination as well as a comprehensive review of the evolution of symptoms over time, relation to possible "triggering" events (eg, fever, infection), blood workup, and family history. High-end neuroimaging plays a pivotal role in establishing diagnosis, narrowing differential diagnosis, monitoring disease progression, and predicting prognosis. The pattern and characteristics of the neuroimaging findings are often highly suggestive of a mitochondrial disorder; unfortunately, in many cases the wide variability of involved metabolic processes prevents a more specific subclassification. Consequently, additional diagnostic steps including muscle biopsy, metabolic workup, and genetic tests are necessary. In the current manuscript, basic concepts of energy production, genetics, and inheritance patterns are reviewed. In addition, the imaging findings of several illustrative mitochondrial disorders are presented to familiarize the involved physicians with pediatric mitochondrial disorders. In addition, the significance of spinal cord imaging and the value of "reversed image-based discovery" for the recognition and correct (re-)classification of mitochondrial disorders is discussed.

Musical Performance in Adolescents with ADHD, ADD and Dyslexia-Behavioral and Neurophysiological Aspects.

Research has shown that dyslexia and attention deficit (hyperactivity) disorder (AD(H)D) are characterized by specific neuroanatomical and neurofunctional differences in the auditory cortex. These neurofunctional characteristics in children with ADHD, ADD and dyslexia are linked to distinct differences in music perception. Group-specific differences in the musical performance of patients with ADHD, ADD and dyslexia have not been investigated in detail so far. We investigated the musical performance and neurophysiological correlates of 21 adolescents with dyslexia, 19 with ADHD, 28 with ADD and 28 age-matched, unaffected controls using a music performance assessment scale and magnetoencephalography (MEG). Musical experts independently assessed pitch and rhythmic accuracy, intonation, improvisation skills and musical expression. Compared to dyslexic adolescents, controls as well as adolescents with ADHD and ADD performed better in rhythmic reproduction, rhythmic improvisation and musical expression. Controls were significantly better in rhythmic reproduction than adolescents with ADD and scored higher in rhythmic and pitch improvisation than adolescents with ADHD. Adolescents with ADD and controls scored better in pitch reproduction than dyslexic adolescents. In pitch improvisation, the ADD group performed better than the ADHD group, and controls scored better than dyslexic adolescents. Discriminant analysis revealed that rhythmic improvisation and musical expression discriminate the dyslexic group from controls and adolescents with ADHD and ADD. A second discriminant analysis based on MEG variables showed that absolute P1 latency asynchrony |R-L| distinguishes the control group from the disorder groups best, while P1 and N1 latencies averaged across hemispheres separate the control, ADD and ADHD groups from the dyslexic group. Furthermore, rhythmic improvisation was negatively correlated with auditory-evoked P1 and N1 latencies, pointing in the following direction: the earlier the P1 and N1 latencies (mean), the better the rhythmic improvisation. These findings provide novel insight into the differences between music processing and performance in adolescents with and without neurodevelopmental disorders. A better understanding of these differences may help to develop tailored preventions or therapeutic interventions.

Pediatric spinal cord diffuse midline glioma, H3 K27-altered with intracranial and spinal leptomeningeal spread: A case report.

Primary spinal cord high-grade gliomas, including those histologically identified as glioblastoma (GBM), are a rare entity in the pediatric population but should be considered in the differential diagnosis of intramedullary lesions. Pediatric spinal cord high-grade gliomas have an aggressive course with poor prognosis. The aim of this case report is to present a 15-year-old female adolescent with histopathologically confirmed spinal cord GBM with H3F3A K27 M mutation consistent with a diffuse midline glioma (DMG), H3 K27-altered, CNS WHO grade 4 with leptomeningeal seeding on initial presentation. As imaging features of H3 K27-altered DMGs are non-specific and may mimic more frequently encountered neoplastic diseases as well as demyelinating disorders, severe neurological deficits at presentation with short duration, rapid progression, and early leptomeningeal seeding should however raise the suspicion for a pediatric-type diffuse high-grade glioma like DMG, H3 K27-altered.

Conventional and advanced MR imaging findings in a cohort of pathology-proven dermoid cysts of the pediatric scalp and skull.

BACKGROUND: In the pediatric population, dermoid cysts are among the most frequent lesions of the scalp and skull. Imaging plays a key role in characterizing scalp and skull lesions in order to narrow the differential diagnoses. In general, dermoids are described as heterogeneous T1-/T2-hypo- to hyperintense lesions on magnetic resonance imaging. METHODS: The goal of this retrospective study is to evaluate the diffusion weighted imaging findings while reviewing the conventional T1-/T2-/T1+C-weighted MR characteristics in a pathology-proven series of 14 dermoids of the pediatric scalp and skull. RESULTS: In our pediatric cohort (eight boys, six girls, age range 3-95 months), half of the dermoids were homogeneous T1-hypointense and homogeneous T2-hyperintense. We found a mixture of restricted (45.5%) and increased diffusion (54.5%) in dermoids. The vast majority of dermoids (91.7%) showed rim enhancement. Most dermoids (57.1%) were located at the midline and adjacent to one of its sutures. CONCLUSIONS: This study suggests that dermoids may have more variable imaging appearances than hitherto assumed and are frequently seen in close proximity or adjacent to the anterior fontanelle.