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The brainstem region, locus coeruleus (LC), has been remarkably conserved across vertebrates. Evolution has woven the LC into wide-ranging neural circuits that influence functions as broad as autonomic systems, the stress response, nociception, sleep, and high-level cognition among others. Given this conservation, there is a strong possibility that LC activity is inherently similar across species, and furthermore that age, sex, and brain state influence LC activity similarly across species. The degree to which LC activity is homogenous across these factors, however, has never been assessed due to the small sample size of individual studies. Here, we pool data from 20 laboratories (1,855 neurons) and show diversity across both intrinsic and extrinsic factors such as species, age, sex and brain state. We use a negative binomial regression model to compare activity from male monkeys, and rats and mice of both sexes that were recorded across brain states from brain slices ex vivo or under different anesthetics or during wakefulness in vivo . LC activity differed due to complex interactions of species, sex, and brain state. The LC became more active during aging, independent of sex. Finally, in contrast to the foundational principle that all species express two distinct LC firing modes ("tonic" or "phasic"), we discovered great diversity within spontaneous LC firing patterns. Different factors were associated with higher incidence of some firing modes. We conclude that the activity of the evolutionarily-ancient LC is not conserved. Inherent differences due to age and species-sex-brain state interactions have implications for understanding the role of LC in species-specific naturalistic behavior, as well as in psychiatric disorders, cardiovascular disease, immunology, and metabolic disorders., Competing Interests: Qi Wang and Charles Rodenkirch are the founders of Sharper Sense, a company developing methods of enhancing sensory processing with neural interfaces. Alfred P. Kaye receives or has received research funding from Transcend Therapeutics and Freedom Biosciences, and has filed a provisional patent for combination psychedelic pharmacotherapies in PTSD. Anthony E Pickering reports research funding from Eli Lilly and is a member of the advisory board for Lateral Pharma. All other authors report no disclosures or conflicts of interest. Nelson K. Totah has filed a provisional patent for a head-fixation attachment for the skull of a rat and method for installing the attachment.

Objective: Natural language processing (NLP) can generate diagnoses codes from imaging reports. Meanwhile, the International Classification of Diseases (ICD-10) codes are the United States' standard for billing/coding, which enable tracking disease burden and outcomes. This cross-sectional study aimed to test feasibility of an NLP algorithm's performance and comparison to radiologists' and physicians' manual coding., Methods: Three neuroradiologists and one non-radiologist physician reviewers manually coded a randomly-selected pool of 200 craniospinal CT and MRI reports from a pool of >10,000. The NLP algorithm ( Radnosis, VEEV, Inc., Minneapolis, MN ) subdivided each report's Impression into "phrases", with multiple ICD-10 matches for each phrase. Only viewing the Impression, the physician reviewers selected the single best ICD-10 code for each phrase. Codes selected by the physicians and algorithm were compared for agreement., Results: The algorithm extracted the reports' Impressions into 645 phrases, each having ranked ICD-10 matches. Regarding the reviewers' selected codes, pairwise agreement was unreliable ( Krippendorff α  =  0.39-0.63 ). Using unanimous reviewer agreement as "ground truth", the algorithm's sensitivity/specificity/F2 for top 5 codes was 0.88/0.80/0.83 , and for the single best code was 0.67/0.82/0.67. The engine tabulated "pertinent negatives" as negative codes for stated findings (e.g. "no intracranial hemorrhage"). The engine's matching was more specific for shorter than full-length ICD-10 codes ( p  =  0.00582x10 -3 )., Conclusions: Manual coding by physician reviewers has significant variability and is time-consuming, while the NLP algorithm's top 5 diagnosis codes are relatively accurate. This preliminary work demonstrates the feasibility and potential for generating codes with reliability and consistency. Future works may include correlating diagnosis codes with clinical encounter codes to evaluate imaging's impact on, and relevance to care., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Alexander M. McKinney reports a relationship with VEEV, Inc. that includes: board membership and equity or stocks. Zeke J. McKinney reports a relationship with VEEV, Inc. that includes: board membership and equity or stocks. Kevin Campbell reports a relationship with VEEV, Inc. that includes: board membership and equity or stocks. Alexander McKinney has patent #US 17/173,123 issued to Assignee., (© 2024 The Authors.)

Background: Perioperative neurocognitive disorders are a major public health issue, although there are no validated neurophysiologic biomarkers that predict cognitive function after surgery. This study tested the hypothesis that preoperative posterior electroencephalographic alpha power, alpha frontal-parietal connectivity, and cerebral oximetry would each correlate with postoperative neurocognitive function., Methods: This was a single-center, prospective, observational study of adult (older than 18 yr) male and female noncardiac surgery patients. Whole-scalp, 16-channel electroencephalography and cerebral oximetry were recorded in the preoperative, intraoperative, and immediate postoperative settings. The primary outcome was the mean postoperative T-score of three National Institutes of Health Toolbox Cognition tests-Flanker Inhibitory Control and Attention, List Sorting Working Memory, and Pattern Comparison Processing Speed. These tests were obtained at preoperative baseline and on the first two postoperative mornings. The lowest average score from the first two postoperative days was used for the primary analysis. Delirium was a secondary outcome (via 3-min Confusion Assessment Method) measured in the postanesthesia care unit and twice daily for the first 3 postoperative days. Last, patient-reported outcomes related to cognition and overall well-being were collected 3 months postdischarge., Results: Sixty-four participants were recruited with a median (interquartile range) age of 59 (48 to 66) yr. After adjustment for baseline cognitive function scores, no significant partial correlation (ρ) was detected between postoperative cognition scores and preoperative relative posterior alpha power (%; ρ = -0.03, P = 0.854), alpha frontal-parietal connectivity (via weight phase lag index; ρ = -0.10, P = 0.570, respectively), or preoperative cerebral oximetry (%; ρ = 0.21, P = 0.246). Only intraoperative frontal-parietal theta connectivity was associated with postoperative delirium (F[1,6,291] = 4.53, P = 0.034). No electroencephalographic or oximetry biomarkers were associated with cognitive or functional outcomes 3 months postdischarge., Conclusions: Preoperative posterior alpha power, frontal-parietal connectivity, and cerebral oximetry were not associated with cognitive function after noncardiac surgery., (Copyright © 2023 American Society of Anesthesiologists. All Rights Reserved.)

Purpose: To evaluate apparent pituitary gland enlargement in patients with Sanfilippo syndrome observed at our institution., Methods: Twelve patients with Sanfilippo syndrome with brain MRI were studied. Anterior, posterior, and whole pituitary volumes were estimated using the prolate ellipsoid volume calculation method (π/6 × L × W × H). Convexity along the upper pituitary margin (Elster's grade) was also measured. These values were compared to two age- and sex-matched groups (normal controls and patients with Hurler syndrome) using one-way ANOVA followed by Tukey's post hoc analysis for multiple comparisons., Results: In the Sanfilippo cohort, the mean whole pituitary volume was 529.9 mm, the mean anterior pituitary volume was 333.4 mm, and the mean posterior pituitary volume was 59.1 mm with Elster's grade of 4.2. In the control cohort, the mean whole pituitary volume was 217.4 mm, the mean anterior pituitary volume was 154.8 mm, and the mean posterior pituitary volume was 28.4 mm with Elster's grade of 2.5. In the Hurler syndrome cohort, the mean whole pituitary volume was 310.0 mm, the mean anterior pituitary volume was 178.2 mm, and the mean posterior pituitary volume was 35.4 mm with Elster's grade of 3.5., Conclusion: In our cohort of patients with Sanfilippo syndrome, whole, anterior, and posterior pituitary volumes and degree of convexity along the upper pituitary border were all significantly greater than controls. The cause of these morphological changes is unclear, as is clinical correlation of the findings., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Telehealth has gained popularity, particularly in the COVID-19 era. The use of telehealth is now being applied to preoperative evaluation clinics in an effort to overcome barriers to antenatal anesthesia assessment of high-risk obstetrical patients., Objectives: The objective of this study is to determine if the quality of antenatal anesthesia telehealth consults of high-risk obstetric patients is comparable to in-person encounters. This is determined by assessing if telehealth consults are feasible and meet the standards of care, as well as the level of patient satisfaction and ease of use as reported by providers., Study Design: This retrospective study assessed patients prior to delivery who completed a video-telehealth anesthesia consultation (51 cases) from November 1st, 2019 to November 30th, 2020 and all of those for patients receiving an in-person anesthesia consultation (171 controls) from November 2017 through October 2019. Our primary hypothesis was that telehealth and in-person consultations would not result in different standards of care. The primary outcome was an indicator of meeting the standard of care, and the difference in proportions between the telehealth and in-person consultation was tested by Fisher's exact test. Our secondary hypotheses were that patients reported high levels of satisfaction and could use telehealth easily and providers could use the platform easily. Secondary outcomes were assessed by using the Consultation and Relational Empathy (CARE) and the Telehealth Usability Questionnaire (TUQ) surveys, respectively., Results: For the primary outcome, 94.1% (48/51) of telehealth and 89.5% (153/171) of in-person visits met the standard of care, indicating no significant difference between groups ( p -value = .4204). The CARE score was 46 [41,50] {median [interquartile range]}, ( p -value < .0001), indicating patient satisfaction with telehealth. The use-average scores on the TUQ for the patient and provider were 6.67 [6.33, 7] and 6 [5.33, 7] respectively, indicating great system usability., Conclusion: This study demonstrates no significant difference in the standard of care between in-person and telehealth visits. Furthermore, telehealth consultation was feasible and associated with high patient satisfaction and platform usability. Preoperative consultation of high-risk obstetric patients using telehealth visits should be routinely considered in clinical practice. Condensation: There is no significant difference in the standard of care between in-person and telehealth antenatal anesthesia consultations, and patients report high satisfaction and platform usability.Telehealth is gaining popularity, but its role in antenatal anesthesia consultation of high risk obstetrical patients has not yet been defined with respect to standard of care, patient satisfaction, and platform usability.There was no significant difference in standard of care between in-person and telehealth antenatal anesthesia consultations, and patients reported high satisfaction and platform usability.Telehealth should be considered as an alternative to in-person antenatal anesthesia consultation of high risk obstetrical patients. It is a particularly attractive alternative to in-person consultation due to cost-savings, increased patient accessibility, and ease of use.

Background: Heterozygous TERT (telomerase reverse transcriptase) promoter mutations (TPMs) facilitate TERT expression and are the most frequent mutation in glioblastoma (GBM). A recent analysis revealed this mutation is one of the earliest events in gliomagenesis. However, no appropriate human models have been engineered to study the role of this mutation in the initiation of these tumors., Method: We established GBM models by introducing the heterozygous TPM in human induced pluripotent stem cells (hiPSCs) using a two-step targeting approach in the context of GBM genetic alterations, CDKN2A/B and PTEN deletion, and EGFRvIII overexpression. The impact of the mutation was evaluated through the in vivo passage and in vitro experiment and analysis., Results: Orthotopic injection of neuronal precursor cells (NPCs) derived from hiPSCs with the TPM into immunodeficient mice did not enhance tumorigenesis compared to TERT promoter wild type NPCs at initial in vivo passage presumably due to relatively long telomeres. However, the mutation recruited GA-Binding Protein and engendered low-level TERT expression resulting in enhanced tumorigenesis and maintenance of short telomeres upon secondary passage as observed in human GBM. These results provide the first insights regarding increased tumorigenesis upon introducing a TPM compared to isogenic controls without TPMs., Conclusion: Our novel GBM models presented the growth advantage of heterozygous TPMs for the first time in the context of GBM driver mutations relative to isogenic controls, thereby allowing for the identification and validation of TERT promoter-specific vulnerabilities in a genetically accurate background., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Neurovascular compression (NVC) has been the primary hypothesis for the underlying mechanism of classical trigeminal neuralgia (TN). However, a substantial body of literature has emerged highlighting notable exceptions to this hypothesis. The purpose of this study is to assess the reliability and diagnostic accuracy of high resolution, high contrast MRI-determined neurovascular contact for TN., Methods: We performed a retrospective, randomized, and blinded parallel characterization of neurovascular interaction and diagnosis in a population of TN patients and controls using four expert reviewers. Performance statistics were calculated, as well as assessments for generalizability using shuffled bootstraps., Results: Fair to moderate agreement (ICC: 0.32-0.68) about diagnosis between reviewers was observed using MRIs from 47 TN patients and 47 controls. On average reviewers performed no better than chance when diagnosing participants, with an accuracy of 0.57 (95% CI 0.40, 0.59) per patient., Conclusion: While MRI is useful in determining structural causes in secondary TN, expert reviewers do no better to only slightly better than chance with distinguishing TN with MRI, despite moderate agreement. Further, the causal role of NVC for TN is not clear, limiting the applicability of MRI to diagnose or prognosticate treatment of TN., Competing Interests: Conflict of interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Telomerase activation counteracts senescence and telomere erosion caused by uncontrolled proliferation. Epidermal growth factor receptor (EGFR) amplification drives proliferation while telomerase reverse transcriptase promoter (TERTp) mutations underlie telomerase reactivation through recruitment of GA-binding protein (GABP). EGFR amplification and TERTp mutations typically co-occur in glioblastoma, the most common and aggressive primary brain tumor. To determine if these two frequent alterations driving proliferation and immortality are functionally connected, we combine analyses of copy number, mRNA, and protein data from tumor tissue with pharmacologic and genetic perturbations. We demonstrate that proliferation arrest decreases TERT expression in a GABP-dependent manner and elucidate a critical proliferation-to-immortality pathway from EGFR to TERT expression selectively from the mutant TERTp through activation of AMP-mediated kinase (AMPK) and GABP upregulation. EGFR-AMPK signaling promotes telomerase activity and maintains telomere length. These results define how the tumor cell immortality mechanism keeps pace with persistent oncogene signaling and cell cycling., Competing Interests: Declaration of interests J.F.C. has ownership interests in Telo Therapeutics., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Posterior reversible encephalopathy syndrome (PRES) is a neurological disorder characterized by headache, seizures, confusion and visual disturbances, as well as potentially reversible neuroimaging findings in most patients after proper treatment. Seizures is one of the most common clinical presentations of PRES. This review summarizes the potential pathophysiology and clinical features of PRES, as well as a multimodal approach to imaging and also briefly discusses the phenomenon of seizures in paediatric population., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: This study was carried out to evaluate the utility of susceptibility-weighted imaging (SWI) in demonstrating retinal hemorrhages (RH) in pediatric head trauma., Methods: Over a period of 7 years 67 children (age 0-4 years) with head trauma and MRI were included as either abusive head trauma (AHT) (n = 23), non-abusive head trauma (NAHT) (n = 38), or indeterminate (n = 6). Two pediatric neuroradiologists jointly reviewed the MR images for the presence of RH and sensitivity and specificity of SWI and T2WI were calculated., Results: The dilated fundoscopic examination (DFE) was positive for RH in 18/23 (78.3%) of the AHT group, 5/38 (13.2%) in the NAHT group, and 4/6 (66.7%) in the indeterminate group. Regarding the SWI MRI findings, SWI was positive for RH in 13/23 (%56.5), while T2WI was positive in 6/23 (%26.1) of the AHT group. Based on utilizing DFE as a standard, the sensitivity and specificity of SWI in the detection of RH was 63% and 100%, respectively and 30% and 100%, respectively on T2WI., Conclusion: Our results suggest that SWI is a useful diagnostic tool for detection of RH in pediatric head trauma in whom DFE is difficult to perform., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

Anesthetics are known to disrupt neural interactions in cortical and subcortical brain circuits. While the effect of anesthetic drugs on consciousness is reversible, the neural mechanism mediating induction and recovery may be different. Insight into these distinct mechanisms can be gained from a systematic comparison of neural dynamics during slow induction of and emergence from anesthesia. To this end, we used functional magnetic resonance imaging (fMRI) data obtained in healthy volunteers before, during, and after the administration of propofol at incrementally adjusted target concentrations. We analyzed functional connectivity of corticocortical and subcorticocortical networks and the temporal autocorrelation of fMRI signal as an index of neural processing timescales. We found that en route to unconsciousness, temporal autocorrelation across the entire brain gradually increased, whereas functional connectivity gradually decreased. In contrast, regaining consciousness was associated with an abrupt restoration of cortical but not subcortical temporal autocorrelation and an abrupt boost of subcorticocortical functional connectivity. Pharmacokinetic effects could not account for the difference in neural dynamics between induction and emergence. We conclude that the induction and recovery phases of anesthesia follow asymmetric neural dynamics. A rapid increase in the speed of cortical neural processing and subcorticocortical neural interactions may be a mechanism that reboots consciousness., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2021. Published by Elsevier Inc.)

Conscious access to sensory information is likely gated at an intermediate site between primary sensory and transmodal association cortices, but the structure responsible remains unknown. We perform functional neuroimaging to determine the neural correlates of conscious access using a volitional mental imagery task, a report paradigm not confounded by motor behavior. Titrating propofol to loss of behavioral responsiveness in healthy volunteers creates dysfunction of the anterior insular cortex (AIC) in association with an impairment of dynamic transitions of default-mode and dorsal attention networks. Candidate subcortical regions mediating sensory gating or arousal (thalamus, basal forebrain) fail to show this association. The gating role of the AIC is consistent with findings in awake participants, whose conscious access is predicted by pre-stimulus AIC activity near perceptual threshold. These data support the hypothesis that AIC, situated at an intermediate position of the cortical hierarchy, regulates brain network transitions that gate conscious access., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Large-scale genome-wide association studies (GWAS) have implicated thousands of germline genetic variants in modulating individuals' risk to various diseases, including cancer. At least 25 risk loci have been identified for low-grade gliomas (LGGs), but their molecular functions remain largely unknown., Methods: We hypothesized that GWAS loci contain causal single nucleotide polymorphisms (SNPs) that reside in accessible open chromatin regions and modulate the expression of target genes by perturbing the binding affinity of transcription factors (TFs). We performed an integrative analysis of genomic and epigenomic data from The Cancer Genome Atlas and other public repositories to identify candidate causal SNPs within linkage disequilibrium blocks of LGG GWAS loci. We assessed their potential regulatory role via in silico TF binding sequence perturbations, convolutional neural network trained on TF binding data, and simulated annealing-based interpretation methods., Results: We built an interactive website (http://education.knoweng.org/alg3/) summarizing the functional footprinting of 280 variants in 25 LGG GWAS regions, providing rich information for further computational and experimental scrutiny. We identified as case studies PHLDB1 and SLC25A26 as candidate target genes of rs12803321 and rs11706832, respectively, and predicted the GWAS variant rs648044 to be the causal SNP modulating ZBTB16, a known tumor suppressor in multiple cancers. We showed that rs648044 likely perturbed the binding affinity of the TF MAFF, as supported by RNA interference and in vitro MAFF binding experiments., Conclusions: The identified candidate (causal SNP, target gene, TF) triplets and the accompanying resource will help accelerate our understanding of the molecular mechanisms underlying genetic risk factors for gliomas., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Most glioblastomas (GBMs) achieve cellular immortality by acquiring a mutation in the telomerase reverse transcriptase ( TERT ) promoter. TERT promoter mutations create a binding site for a GA binding protein (GABP) transcription factor complex, whose assembly at the promoter is associated with TERT reactivation and telomere maintenance. Here, we demonstrate increased binding of a specific GABPB1L-isoform-containing complex to the mutant TERT promoter. Furthermore, we find that TERT promoter mutant GBM cells, unlike wild-type cells, exhibit a critical near-term dependence on GABPB1L for proliferation, notably also posttumor establishment in vivo. Up-regulation of the protein paralogue GABPB2, which is normally expressed at very low levels, can rescue this dependence. More importantly, when combined with frontline temozolomide (TMZ) chemotherapy, inducible GABPB1L knockdown and the associated TERT reduction led to an impaired DNA damage response that resulted in profoundly reduced growth of intracranial GBM tumors. Together, these findings provide insights into the mechanism of cancer-specific TERT regulation, uncover rapid effects of GABPB1L-mediated TERT suppression in GBM maintenance, and establish GABPB1L inhibition in combination with chemotherapy as a therapeutic strategy for TERT promoter mutant GBM., Competing Interests: Competing interest statement: The Regents of the University of California have patents issued and pending for CRISPR technologies on which J.A.D. is an inventor. C.F. is a co-founder of Mirimus, Inc. J.A.D. is a co-founder of Caribou Biosciences, Editas Medicine, Intellia Therapeutics, Scribe Therapeutics, and Mammoth Biosciences. J.A.D. is a scientific advisory board member of Caribou Biosciences, Intellia Therapeutics, eFFECTOR Therapeutics, Scribe Therapeutics, Synthego, Metagenomi, Mammoth Biosciences, and Inari. J.A.D. is a Director at Johnson & Johnson and has sponsored research projects by Pfizer, Roche Biopharma, and Biogen. J.F.C. is a co-founder of Telo Therapeutics, Inc. and has ownership interests. The other authors declare no competing interests., (Copyright © 2021 the Author(s). Published by PNAS.)

Background and Purpose: This study aimed to assess characteristic regions of MRI involvement utilizing diffusion weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) at urea cycle disorder (UCD) diagnosis to determine the possible association between initial MRI patterns within 10 days of the first hyperammonemia episode, serum ammonia levels, and severity of neurological outcome based on clinical follow-up of >30 days., Methods: Ten patients with UCDs (4 females; median age: 5.4 years, age range: 6 days-54 years) were included who underwent MRI during a first episode of hyperammonemia. The topographical distribution of the DWI and FLAIR abnormalities in the cerebral cortex, deep gray matter, white matter, posterior limb of internal capsule, cerebral peduncle, and cerebellum was evaluated. Possible correlations between the brain injury patterns on DWI/FLAIR images, serum ammonia levels, and severity of neurological outcome were investigated by a trend correlation., Results: The UCD cohort (n = 10) involved four ornithine transcarbamoylase deficiencies, four argininosuccinic aciduria, one carbomoylphosphate synthetase deficiency, and one citrullinemia type-1. The observed trend in the distribution of DWI abnormalities as the severity of neurological sequela outcome increased was with diffuse cerebral cortex or corpus striatum involvement. Patients with initial peak serum ammonia ≥450 µmol/L had a grade 2 to 4 outcome, and those with peak ammonia <450 µmol/L had a grade 0 or 1 outcome., Conclusions: The presence of more severe neurological outcome could be associated with diffuse cerebral cortex or corpus striatum involvement on DWI and high serum ammonia levels in patients with UCD., (© 2020 American Society of Neuroimaging.)

Background: The objective of this study was to test whether postoperative electroencephalographic (EEG) biomarkers, parietal alpha power and frontal-parietal connectivity, were associated with measures of clinical recovery in adult surgical patients., Methods: This is a secondary analysis of a prospective cohort study that analyzed intraoperative connectivity patterns in adult surgical patients (N=53). Wireless, whole-scalp EEG data were collected in the postanesthesia care unit and assessed for relevance to clinical and neurocognitive recovery. Parietal alpha power and frontal-parietal connectivity (estimated by weighted phase lag index) were tested for associations with postanesthesia care unit discharge readiness and University of Michigan Sedation Scale scores upon postoperative admission. Bivariable correlation and regression models were constructed to test for unadjusted associations, then multivariable regression models were constructed to adjust for confounding., Results: Postoperative EEG patterns were characterized by a predominance of alpha parietal power and frontal-parietal connectivity. Neither relative parietal alpha power (% alpha, -0.25; 95% confidence interval [CI], -1.41 to 0.90; P=0.657) nor alpha frontal-parietal connectivity (weighted phase lag index, -82; 95% CI, -237 to 73; P=0.287) were associated with time until postanesthesia discharge criteria were met. Furthermore, neither alpha power (-0.03; 95% CI, -0.07 to 0.01; P=0.206) nor alpha frontal-parietal connectivity (-4.2; 95% CI, -11 to 2.6; P=0.226) were associated with sedation scores upon initial assessment., Conclusions: In a pragmatic study investigating clinically relevant endpoints of postoperative recovery, we found no correlation with surrogate measures of brain neurodynamics. These data contribute to the overall impetus of developing anesthetic-invariant and generalizable markers of brain recovery.

Background and Purpose: Children receiving chemotherapy, or immunosuppression have an increased risk for pediatric posterior reversible encephalopathy syndrome (pPRES); pPRES is scantly described in cerebral X-linked adrenoleukodystrophy (cALD) patients, for which hematopoietic stem cell transplantation improves outcomes. This study aimed to describe distinctive lesion patterns, distribution, and evolution of neuroimaging findings in PRES in a single-center pediatric cohort of cALD., Methods: We retrospectively identified all clinically acquired brain MRIs of children with cALD at a tertiary care university hospital between 1995 and 2020. We reviewed clinical features, conventional MRI, and diffusion-weighted imaging findings of patients with gray matter and white matter (WM) changes suggestive of concurrent PRES-cALD. Associations between the distinctive anatomic features, distribution, and abnormal signal intensity on MRI were examined with regard to the etiology and clinical outcome., Results: Our search revealed a series of eight pediatric cALD patients presenting with seizures, headache, or altered mental status with MRI findings suggestive of both PRES and cALD simultaneously. In each, the cortical-subcortical vasogenic edema on fluid-attenuated inversion recovery was consistent with pPRES, overlying the periventricular WM (PVWM) involvement typical of cALD. Of these 8 patients, the cortical-subcortical lesions on FLAIR were completely reversible on follow-up MRI in 7, but only partially reversible in 1., Conclusions: It is crucial to recognize that pPRES can occur in cALD, notably, the cortical edema and leptomeningeal enhancement can accelerate the diagnosis of superimposed pPRES, while the PVWM lesions of cALD remain following the resolution of pPRES., (© 2020 American Society of Neuroimaging.)

"Encephalopathy" is a vague term that encompasses varying definitions, often with a nonspecific clinical presentation and numerous possible pathophysiologic causes. Hence, MR imaging plays a crucial role in the early diagnosis and treatment by identifying imaging patterns when there is limited clinical history in such patients with acute encephalopathy. The aim of this review was to aid in remembrance of etiologies of potentially reversible acute encephalopathic syndromes on MR imaging. The differential includes vascular (reversible cerebral vasoconstriction syndrome, transient global amnesia, disseminated intravascular coagulation, and thrombotic microangiopathy), infection (meningitis, encephalitis), toxic (posterior reversible encephalopathy syndrome, acute toxic leukoencephalopathy; carbon monoxide, alcohol-related, medication- and illicit drug-related toxic encephalopathies), autoimmune, metabolic (osmotic demyelination syndrome, uremic, acute hepatic encephalopathy), idiopathic/inflammatory (stroke-like migraine attacks after radiation therapy syndrome), neoplasm-related encephalopathy, and seizure-related encephalopathy., (© 2020 by American Journal of Neuroradiology.)

Background and Purpose: Pediatric acute toxic leukoencephalopathy is a clinicoradiologic entity comprising various etiologies. This study aimed to identify the MR imaging appearance of pediatric acute toxic leukoencephalopathy from various etiologies and determine whether the etiology correlates with clinical outcome., Materials and Methods: We retrospectively reviewed the electronic records of patients with pediatric acute toxic leukoencephalopathy younger than 19 years of age who had MR imaging within <2 weeks of presentation, including DWI and FLAIR sequences. Two neuroradiologists scored the DWI and FLAIR severity and measured the percentage ADC reduction within the visibly affected regions and normal-appearing WM. The percentage ADC reduction and DWI and FLAIR severity were correlated with clinical outcome using the Spearman correlation., Results: Of 22 children, 3 were excluded due to a nontoxic cause or incomplete examination. Regarding the included 19 children (mean age, 13 years), the etiologies of pediatric acute toxic leukoencephalopathy were the following: methotrexate ( n =  6), bone marrow transplantation ( n  = 4), fludarabine ( n =  3), cytarabine ( n =  1), carboplatin ( n =  1), vincristine ( n = 1 ), cyclosporine ( n =  1), uremia ( n =  1), and bevacizumab ( n =  1). Three subgroups were analyzed (chemotherapy, n =  12; immunosuppression, n =  5; others, n =  2). There was a strong correlation of FLAIR ( r   =  0.773 , P  < .001) and DWI ( r =  0.851 , P  < .001) severity with clinical outcome, and patients treated with fludarabine had the worst outcomes. High percentage ADC reduction values were associated with adverse outcomes, and lower percentage ADC reduction values were associated with favorable outcomes ( r =  0.570 , P  = .011)., Conclusions: The DWI and FLAIR severity scores appear highly prognostic, whereas percentage ADC reduction is moderately prognostic for clinical outcomes in pediatric acute toxic leukoencephalopathy. Immunosuppressive pediatric acute toxic leukoencephalopathy tends toward favorable outcomes, and fludarabine tends toward worse outcomes., (© 2020 by American Journal of Neuroradiology.)

Background and Purpose: The conventional fluoroscopy-guided (CF) selective cervical nerve root block (SCNRB) is being used commonly as a treatment for cervical radicular pain as well as a diagnostic tool. This study aimed to identify any major complications and determine the safety and clinical utility of CF-SCNRB performed in a university hospital and associated outpatient clinics., Materials and Methods: Two-hundred fifty-four conventional fluoroscopy-guided selective cervical nerve root blocks were retrospectively identified from 2011 to 2018 using a radiology report search tool. Each procedure was performed by an experienced neuroradiologist performing spinal injections on a full-time basis in clinical practice. A 10-point pain scale was used for pre- and postprocedural pain-level assessment. Successful conventional, fluoroscopy-guided, selective cervical nerve root block was defined as a patient-reported pain scale reduction of at least 50% and/or alleviation of numbness or paresthesia at ≥2 weeks postinjection. All clinically important immediate and delayed complications were also recorded., Results: Two-hundred fifty-four conventional fluoroscopy-guided selective cervical nerve root blocks were performed via an anterolateral approach with an average fluoroscopy time of 24.3 seconds for all cases. There were no aborted procedures and no major or permanent complications. There were 14 minor complications; 12 of these were periprocedural and resolved by the 2-week follow-up visit. One-hundred eighty-five patients (75.2%) reported pain improvement of >50% from baseline at 15 minutes postinjection. Overall, 172 patients (67.7%) reported >50% pain scale reduction or alleviation from paresthesia at least 2 weeks postinjection., Conclusions: Conventional fluoroscopy-guided selective cervical nerve root block is an efficacious, efficient, and safe outpatient procedure when performed by a skilled and experienced proceduralist., (© 2020 by American Journal of Neuroradiology.)

The need for a guidance document on MR safe practices arose from a growing awareness of the MR environment's potential risks and adverse event reports involving patients, equipment, and personnel. Initially published in 2002, the American College of Radiology White Paper on MR Safety established de facto industry standards for safe and responsible practices in clinical and research MR environments. The most recent version addresses new sources of risk of adverse events, increases awareness of dynamic MR environments, and recommends that those responsible for MR medical director safety undergo annual MR safety training. With regular updates to these guidelines, the latest MR safety concerns can be accounted for to ensure a safer MR environment where dangers are minimized. Level of Evidence: 1 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2020;51:331-338., (© 2019 International Society for Magnetic Resonance in Medicine.)

Toxic and metabolic brain disorders are relatively uncommon diseases that affect the central nervous system, but they are important to recognize as they can lead to catastrophic outcomes if not rapidly and properly managed. Imaging plays a key role in determining the most probable diagnosis, pointing to the next steps of investigation, and providing prognostic information. The majority of cases demonstrate bilateral and symmetric involvement of structures at imaging, affecting the deep gray nuclei, cortical gray matter, and/or periventricular white matter, and some cases show specific imaging manifestations. When an appropriate clinical situation suggests exogenous or endogenous toxic effects, the associated imaging pattern usually indicates a restricted group of diagnostic possibilities. Nonetheless, toxic and metabolic brain disorders in the literature are usually approached in the literature by starting with common causal agents and then reaching imaging abnormalities, frequently mixing many different possible manifestations. Conversely, this article proposes a systematic approach to address this group of diseases based on the most important imaging patterns encountered in clinical practice. Each pattern is suggestive of a most likely differential diagnosis, which more closely resembles real-world scenarios faced by radiologists. Basic pathophysiologic concepts regarding cerebral edemas and their relation to imaging are introduced-an important topic for overall understanding. The most important imaging patterns are presented, and the main differential diagnosis for each pattern is discussed. Online supplemental material is available for this article. © RSNA, 2019.

Purpose: Septo-optic dysplasia is a congenital disorder consisting of optic nerve hypoplasia and absent septum pellucidum. While associated anomalies have been described, olfactory sulcus and bulb-tract hypoplasia have been scantily reported and was the focus of this study., Methods: The picture archival and communications system and radiology information system (PACS-RIS) was searched over 15 years for patients with suspected septo-optic dysplasia (n = 41) and cerebral magnetic resonance imaging (MRI). Included patients had coronal (≤3 mm), axial (≤4 mm), and sagittal (≤4 mm) imaging reviewed by two staff neuroradiologists by consensus. Both olfactory sulcus and bulb-tract hypoplasia were ascribed a grade of 0 (normal) to 3 (complete hypoplasia). Other associated congenital anomalies were recorded, if present. Incidence of anomalies were compared to age-matched and gender-matched control patients., Results: Out of 41 septo-optic dysplasia patients 33 were included (mean age = 120.7 months), with 8 excluded due to isolated septum pellucidum absence (n = 5), isolated bilateral optic hypoplasia (n = 2), or inadequate imaging (n = 1). An olfactory sulcus was hypoplastic on one or both sides in 14/33 (42.4%). Olfactory bulb hypoplasia was noted in one or both tracts in 15/33 (45.4%). A significant correlation was found between degree of olfactory sulcal and bulb-tract hypoplasia (ρ = 0.528, p = 0.0009). Other anomalies were: anterior falx dysplasia (n = 16, 48.5%), incomplete hippocampal inversion (n = 14, 42.4%), polymicrogyria (n = 11, 33.3%), callosal complete or partial agenesis (n = 10, 30.3%), schizencephaly (n = 8, 24.2%), ectopic posterior pituitary (n = 6, 18.2%), and nodular heterotopia (n = 4, 12.1%). Of the age-matched control patients 10/33 (30.3%) had at least mild anterior falx hypoplasia, and 1 control patient was noted to have unilateral incomplete hippocampal inversion (IHI); none of the age-matched control patients had olfactory sulcus or bulb-tract hypoplasia., Conclusion: Olfactory sulcus and bulb-tract hypoplasia are fairly common in septo-optic dysplasia and can be discordant between sides. Of the other associated anomalies, anterior falx dysplasia seems to be the most common.

Purpose: To describe non-metabolic, non-infectious etiologies of acute toxic leukoencephalopathy (ATL) on DWI MRI, and provide a useful acronym to remember them., Material and Methods: Our PACS archive was reviewed, yielding 185 patients with suspected ATL per MRI reports and clinical follow up; infectious or metabolic causes were excluded., Result/discussion: The 87 included non-infectious, non-metabolic ATL patients' etiologies are represented by the acronym 'CHOICES': chemotherapy ('C',n = 34); heroin-induced ('H',n = 6), opioid analogues ('O',n = 14); immunosuppressant ('I',n = 11) or imidazole (n = 2); cocaine ('C',n = 1); environmental or ethanol abuse ('E',n = 5), splenial lesions ('S',n = 9), and 'other' (n = 5)., Conclusion: The "CHOICES" acronym delineates various toxic etiologies of ATL.

Background: Functional connectivity across the cortex has been posited to be important for consciousness and anesthesia, but functional connectivity patterns during the course of surgery and general anesthesia are unknown. The authors tested the hypothesis that disrupted cortical connectivity patterns would correlate with surgical anesthesia., Methods: Surgical patients (n = 53) were recruited for study participation. Whole-scalp (16-channel) wireless electroencephalographic data were prospectively collected throughout the perioperative period. Functional connectivity was assessed using weighted phase lag index. During anesthetic maintenance, the temporal dynamics of connectivity states were characterized via Markov chain analysis, and state transition probabilities were quantified., Results: Compared to baseline (weighted phase lag index, 0.163, ± 0.091), alpha frontal-parietal connectivity was not significantly different across the remaining anesthetic and perioperative epochs, ranging from 0.100 (± 0.041) to 0.218 (± 0.136) (P > 0.05 for all time periods). In contrast, there were significant increases in alpha prefrontal-frontal connectivity (peak = 0.201 [0.154, 0.248]; P < 0.001), theta prefrontal-frontal connectivity (peak = 0.137 [0.091, 0.182]; P < 0.001), and theta frontal-parietal connectivity (peak = 0.128 [0.084, 0.173]; P < 0.001) during anesthetic maintenance. Additionally, shifts occurred between states of high prefrontal-frontal connectivity (alpha, beta) with suppressed frontal-parietal connectivity, and high frontal-parietal connectivity (alpha, theta) with reduced prefrontal-frontal connectivity. These shifts occurred in a nonrandom manner (P < 0.05 compared to random transitions), suggesting structured transitions of connectivity during general anesthesia., Conclusions: Functional connectivity patterns dynamically shift during surgery and general anesthesia but do so in a structured way. Thus, a single measure of functional connectivity will likely not be a reliable correlate of surgical anesthesia.

Background and Purpose: Differentiating Abusive Head Trauma (AHT) from Non-abusive Head trauma (NAHT) has profound clinical prognostic and legal implications, as certain imaging findings can individually be more suggestive of NAHT, while others are more suggestive of AHT. This study was set out to evaluate for an association between the various imaging findings in AHT with outcome., Material and Methods: Over 7-years, 55 children (age 0-4 years') with head trauma and magnetic resonance imaging (MRI) were included as either: abusive (n = 16), non-abusive (n = 35), or indeterminate (n = 4). Two pediatric neuroradiologists jointly reviewed the imaging. The frequency of imaging findings and their association with ≥6 months' outcome were calculated., Results: Comparing abusive versus non-abusive head trauma, complex subdural hematoma was present in 81% (n = 13/16) and 29% (n = 10/35), hypoxic-ischemic injury in 44% (n = 7/16) and 6% (n = 2/35), and diffuse axonal injury in 12% (n = 2/16) and 26% (n = 9/35), respectively. Susceptibility-weighted imaging (SWI) retinal hemorrhages were absent in non-abusive trauma (0/35), but present in 44% (n = 7/16) of the abusive group. In abuse, simple subdural hematomas were absent. Significant associations were found between the presence of abusive trauma with both hypoxic ischemic insult (OR = 12.83, p = 0.0024) and complex subdural hematoma (OR = 10.83, p = 0.0007). The presence of hypoxic ischemic injury (HII) did correlate significantly with clinical outcome (p = 0.017), while retinal hemorrhages on SWI and complex subdural hematoma did not (p = 0.1696-p = 0.2496)., Conclusion: Neuroimaging findings can be helpful in discriminating these two conditions on presentation, as well as in helping solidify the suspicion of AHT. Regarding eventual outcome in AHT, the most important predictor is clearly HII.

Background: Cognitive training is beneficial in various clinical settings, although its perioperative feasibility and impact remain unknown. The objective of this pilot study was to determine the feasibility of home-based cognitive prehabilitation before major surgery in older adults., Materials and Methods: Sixty-one patients were enrolled, randomized, and allocated to either a home-based preoperative cognitive training regimen or no training before surgery. Outcomes included postoperative delirium incidence (primary outcome; assessed with the 3D-Confusion Assessment Method), perioperative cognitive function based on NIH Toolbox measures, hospital length of stay, and physical therapy session participation. Reasons for declining enrollment were reported, as were reasons for opting out of the training program., Results: Postoperative delirium incidence was 6 of 23 (26%) in the prehabilitation group compared with 5 of 29 (17%) in the control group (P=0.507). There were no significant differences between groups in NIH Toolbox cognitive function scoring, hospital length of stay, or physical therapy participation rates. Study feasibility data were also collected and reported. The most common reasons for declining enrollment were lack of computer access (n=19), time commitment (n=9), and feeling overwhelmed (n=9). In the training group, only 5 of 29 (17%) included patients were able to complete the prescribed 7 days of training, and 14 of 29 (48%) opted out of training once home. Most common reasons were feeling overwhelmed (n=4) and computer difficulties (n=3)., Conclusions: Short-term, home-based cognitive training before surgery is unlikely to be feasible for many older patients. Barriers to training include feeling overwhelmed, technical issues with training, and preoperative time commitment.

Background and Purpose: Prior studies regarding acute toxic leukoencephalopathy (ATL) are either small, or preliminary. Our aim was to evaluate etiologies of and differences in imaging severity and outcomes among various etiologies of ATL., Materials and Methods: MRIs of patients with suspected ATL over 15 years were retrospectively reviewed; inclusion criteria were: MRI <3 weeks of presentation with both DWI and FLAIR. These were jointly graded by two neuroradiologists via a previously described score of severity. Clinical outcome was evaluated via both modified Rankin (mRS) and ATL outcome (ATLOS) scores, each being correlated with the DWI and FLAIR scores. Etiologic subgroups of n > 6 patients were statistically compared., Results: Of 101 included patients, the 4 subgroups of n > 6 were the following: chemotherapy ( n = 35), opiates ( n = 19), acute hepatic encephalopathy ( n = 14), and immunosuppressants ( n = 11). Other causes ( n = 22 total) notably included carbon monoxide ( n = 3) metronidazole ( n = 2), and uremia ( n = 1). The mean DWI/FLAIR severity scores were 2.6/2.3, 3.3/3.3, 2.1/2.1 and 2.0/2.5 for chemotherapeutics, opiates, AHE and immunosuppressants, respectively, with significant differences in both imaging severity and outcome ( P = .003-.032) among subgroups, particularly immunosuppressant versus chemotherapy-related ATL and immunosuppressants versus opiates ( P = .004-.032) related ATL. DWI and FLAIR severity weakly correlated with outcome (ρ = 0.289-.349, P < .005) but correlated stronger in the chemotherapy (ρ = 0.460-.586, P < .010) and opiate (ρ =.472-.608, P < .05) subgroups, which had the worst outcomes. ATL clinically resolved in 36%, with severe outcomes in 23% (coma or death, 9/16 deaths from fludarabine). Notable laboratory results were elevated CSF myelin basic protein levels in 8/9 patients and serum blood urea nitrogen levels in 24/91., Conclusions: Clinical outcomes of ATL vary on the basis of etiology, being worse in chemotherapeutic- and opiate-related ATL. Uremia may be a predisposing or exacerbating factor., (© 2019 by American Journal of Neuroradiology.)

Objective: The supply territories of main cerebral arteries are predominantly identified based on distribution of infarct lesions in patients with large arterial occlusion; whereas, there is no consensus atlas regarding the supply territories of smaller end-arteries. In this study, we applied a data-driven approach to construct a stroke atlas of the brain using hierarchical density clustering in large number of infarct lesions, assuming that voxels/regions supplied by a common end-artery tend to infarct together., Methods: A total of 793 infarct lesions on MRI scans of 458 patients were segmented and coregistered to MNI-152 standard brain space. Applying a voxel-wise data-driven hierarchical density clustering algorithm, we identified those voxels that were most likely to be part of same infarct lesions in our dataset. A step-wise clustering scheme was applied, where the clustering threshold was gradually decreased to form the first 20 mother (>50 cm 3 ) or main (1-50 cm 3 ) clusters in addition to any possible number of tiny clusters (<1 cm 3 ); and then, any resultant mother clusters were iteratively subdivided using the same scheme. Also, in a randomly selected 2/3 subset of our cohort, a bootstrapping cluster analysis with 100 permutations was performed to assess the statistical robustness of proposed clusters., Results: Approximately 91% of the MNI-152 brain mask was covered by 793 infarct lesions across patients. The covered area of brain was parcellated into 4 mother, 16 main, and 123 tiny clusters at the first hierarchy level. Upon iterative clustering subdivision of mother clusters, the brain tissue was eventually parcellated into 1 mother cluster (62.6 cm 3 ), 181 main clusters (total volume 1107.3 cm 3 ), and 917 tiny clusters (total volume of 264.8 cm 3 ). In bootstrap analysis, only 0.12% of voxels, were labelled as "unstable" - with a greater reachability distance in cluster scheme compared to their corresponding mean bootstrapped reachability distance. On visual assessment, the mother/main clusters were formed along supply territories of main cerebral arteries at initial hierarchical levels, and then tiny clusters emerged in deep white matter and gray matter nuclei prone to small vessel ischemic infarcts., Conclusions: Applying voxel-wise data-driven hierarchical density clustering on a large number of infarct lesions, we have parcellated the brain tissue into clusters of voxels that tend to be part of same infarct lesion, and presumably representing end-arterial supply territories. This hierarchical stroke atlas of the brain is shared publicly, and can potentially be applied for future infarct location-outcome analysis., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Acute encephalopathic syndromes can present a diagnostic challenge due to the wide range of possible etiologies, which also can have vastly different outcomes. The presence of diffuse cortical injury (DCI) on diffusion-weighted imaging (DWI) can help narrow the differential diagnosis. The aim of this review is to categorize the range of possible etiologies of DCI into a useful acronym, "CRUMPLED"., Methods: A review of the PACS system was completed to find a characteristic example of patients with DCI on DWI from different etiologies. The diagnosis was confirmed for each example via a subsequent review of the electronic medical record used to assess for data such as biopsy results, laboratory values, and clinical correlation. The electronic exhibit intends to demonstrate several sample cases of each letter within the acronym, and to demonstrate which types of DCI are potentially reversible or irreversible., Findings/discussion: The possible etiologies of DCI on DWI can be organized using the acronym "CRUMPLED": 'C' = Creutzfeldt-jakob disease, 'R' =  reversible cerebral vasoconstriction syndrome; 'U' = urea cycle disorders (hyperammonemia) and Uremia; 'M' = mitochondrial (cytopathy/encephalopathy); 'P' = prolonged seizure and posterior reversible encephalopathy (PRES); 'L' = laminar necrosis (hypoxic-ischemic encephalopathy) and liver disease (acute hepatic encephalopathy); 'E' = encephalitis (infectious meningoencephalitis); 'D' = diabetes mellitus (hypoglycemia). Other secondary imaging findings (outside of DWI) can be used to help differentiate between the aforementioned etiologies, such as the use of ADC maps, FLAIR imaging, intravenous contrast., Conclusion: "CRUMPLED" is proposed as a convenient acronym for the categorization of a diverse range of acute etiologies associated with DCI on DWI, arising from varying degrees of cytotoxic edema. These etiologies can range from being potentially reversible (e.g. hyperammonemia or prolonged seizures) to irreversible (e.g. hypoxic-ischemic injury).

TERT promoter mutations reactivate telomerase, allowing for indefinite telomere maintenance and enabling cellular immortalization. These mutations specifically recruit the multimeric ETS factor GABP, which can form two functionally independent transcription factor species: a dimer or a tetramer. We show that genetic disruption of GABPβ1L (β1L), a tetramer-forming isoform of GABP that is dispensable for normal development, results in TERT silencing in a TERT promoter mutation-dependent manner. Reducing TERT expression by disrupting β1L culminates in telomere loss and cell death exclusively in TERT promoter mutant cells. Orthotopic xenografting of β1L-reduced, TERT promoter mutant glioblastoma cells rendered lower tumor burden and longer overall survival in mice. These results highlight the critical role of GABPβ1L in enabling immortality in TERT promoter mutant glioblastoma., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Detecting covert consciousness in behaviorally unresponsive patients by brain imaging is of great interest, but a reproducible model and evidence from independent sources is still lacking. Here we demonstrate the possibility of using general anesthetics in a within-subjects study design to test methods or statistical paradigms of assessing covert consciousness. Using noninvasive neuroimaging in healthy volunteers, we identified a healthy study participant who was able to exhibit the specific fMRI signatures of volitional mental imagery while behaviorally unresponsive due to sedation with propofol. Our findings reveal a novel model that may accelerate the development of new approaches to reproducibly detect covert consciousness, which is difficult to achieve in patients with heterogeneous and sometimes clinically unstable neuropathology.

Background and Purpose: Posterior reversible encephalopathy syndrome (PRES) and acute toxic leukoencephalopathy (ATL) are both potentially reversible clinicoradiologic entities. Although their magnetic resonance imaging (MRI) findings differ, rarely both may occur simultaneously in acutely encephalopathic patients. Our aim was to determine the incidence and causes of concomitant "ATL-PRES.", Methods: Retrospective search of suspected acutely encephalopathic adults since 1998 throughout our picture archiving and communication system revealed 167 patients with PRES and 106 patients with ATL. Images of these patients were retrospectively evaluated by two neuroradiologists and a fellow to identify the cases which carry both features of PRES and ATL. Imaging findings were scored based on previously reported scoring system as mild, moderate, and severe. The clinical outcome of the patients was determined according to the modified Rankin scale., Results: Our search revealed a series of 6 patients (%2.2) in 273 patients who presented acutely with either encephalopathy or seizures, caused by various etiologies, including immunosuppression following transplantation (n = 2), hypertensive crisis (n = 2), chemotherapy (n = 1), and sepsis (n = 1). MRI demonstrated findings consistent with both PRES and ATL simultaneously on FLAIR and diffusion weighted imaging. Severity of imaging findings of concomitant "ATL-PRES" was concordant with each other (rho ≈ 1.0, P < .00001), and each patient eventually returned to clinical baseline. This finding, along with their similar etiologies, raises the possibility of an underlying common pathophysiologic thread, perhaps being endothelial toxicity., Conclusions: Concomitant "ATL-PRES" was found in 2.2% of the patients in a large cohort of ATL and PRES. Etiologies varied. Clinical symptoms and MRI findings were potentially reversible., (© 2018 by the American Society of Neuroimaging.)

Background and Purpose: Propofol is a cerebral vasoconstrictor that modulates cerebral perfusion by decreasing the metabolic rate of oxygen. Because younger children often undergo intravenous sedation for MR imaging, this study set out to evaluate the degree of leptomeningeal contrast enhancement on 3T postcontrast brain MR imaging and to determine whether this phenomenon relates to sequence, sedation dosage, or patient age or weight., Materials and Methods: During a 2-year period, of 152 children 1-5 years of age who underwent MR imaging, 43 were included for MRI review. Of these, 37 underwent postcontrast imaging with either solely gradient-echo T1WI ( n = 20) or spin-echo T1WI ( n = 17); notably, 6 patients underwent both sequences. Three neuroradiologists separately graded the degree of leptomeningeal contrast enhancement (grades 0-3) that was correlated with various factors and calculated the interobserver reliability., Results: For the 43 patients, the mean patient age was 3.1 ± 1.4 years. The leptomeningeal contrast-enhancement grade was significantly greater ( P < .0001) on spin-echo T1WI (1.9-2.1) versus gradient-echo TIWI (1.2-1.4). Patient weight ( r = -0.366 to -.418, P = .003-.01) and age ( r = -0.315 to -0.418, P = .004-.032) moderately and inversely correlated with the leptomeningeal contrast-enhancement grade, while the propofol dosage, sedation duration, and time to T1WI post-contrast administration did not (each, P > .05). The interobserver κ was strong regarding the leptomeningeal contrast-enhancement grade on both spin-echo T1WI (κ = 0.609-0.693, P < .0001) and gradient-echo TIWI (κ = 0.567-0.698, P < .0001)., Conclusions: Leptomeningeal contrast enhancement (or "pseudo"-leptomeningeal contrast enhancement) occurs with a greater frequency and degree on 3T postcontrast spin-echo T1WI relative to gradient-echo TIWI in younger children sedated with propofol and should not be mistaken for disease. This phenomenon may be more prominent with lower age or size and may arise from propofol-induced vascular smooth-muscle dilation., (© 2018 by American Journal of Neuroradiology.)

Interlaminar lumbar puncture and cervical puncture may not be ideal in all circumstances. Recently, we have used a transforaminal approach in selected situations. Between May 2016 and December 2017, twenty-six transforaminal lumbar punctures were performed in 9 patients (25 CT-guided, 1 fluoroscopy-guided). Seven had spinal muscular atrophy and were referred for intrathecal nusinersen administration. In 2, CT myelography was performed via transforaminal lumbar puncture. The lumbar posterior elements were completely fused in 8, and there was an overlying abscess in 1. The L1-2 level was used in 2; the L2-3 level, in 10; the L3-4 level, in 12; and the L4-5 level, in 2 procedures. Post-lumbar puncture headache was observed on 4 occasions, which resolved without blood patching. One patient felt heat and pain at the injection site that resolved spontaneously within hours. One patient had radicular pain that resolved with conservative treatment. Transforaminal lumbar puncture may become an effective alternative to classic interlaminar lumbar puncture or cervical puncture., (© 2018 by American Journal of Neuroradiology.)

Background: The information on topographic distribution of acute ischemic infarct can contribute to prediction of functional outcome. We aimed to develop a multivariate model for stroke prognostication, combining admission clinical and imaging variables, including the infarct topology., Methods: Acute ischemic stroke patients without baseline functional disability who had magnetic resonance imaging within 24 hours of onset or last-seen-well were included. The admission stroke severity was determined using the National Institutes of Health Stroke Scale (NIHSS) score. The relation between infarct location and outcome was assessed using both voxel-based and visual atlas-based analyses. The disability/death was defined by a modified Rankin Scale score greater than 2 at 3-month follow-up., Results: Among 198 patients included in this study, higher admission NIHSS score (P < .001), larger infarct volume (P < .001), and major arterial occlusions (P < .001) were associated with disability/death in univariate analyses. On voxel-based analysis, infarcts in the middle centrum semiovale, insula, and midbrain/pons were associated with higher rates of disability/death. In multivariate analysis, admission NIHSS score (P < .001), infarction of insula (P = .005), and midbrain/pons (P = .006) were independent predictors of disability/death. In receiver operating characteristics analysis, a simple 0-to-3 scoring system using these 3 variables had an area under the curve of .812 for prediction of disability/death (P < .001)., Conclusions: Admission symptom severity, infarction of insula, and midbrain/pons were independent predictors of clinical outcome in acute ischemic stroke patients. The methodology of this hypothesis-generating study can help conceive quantitative population-based probabilistic models for prognostication or treatment triage in stroke patients, combining admission clinical and imaging findings-including infarct topography., (Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: Neurotoxoplasmosis is a common opportunistic infection in HIV/AIDS patients. Imaging identification of neurotoxoplasmosis assists in timely treatment., Purpose: To delineate the frequency of imaging abnormalities in patients with neurotoxoplasmosis on different MR sequences with a particular focus on SWI, and NCCT., Material and Methods: The PACS database was retroactively searched over a 5-year period for patients with neurotoxoplasmosis who underwent MRI with SWI. Included patients had imaging features of neurotoxoplasmosis based on consensus review by two neuroradiologists, a clinical diagnosis of neurotoxoplasmosis at the time of MRI, and diagnostic confirmation based on positive serum or CSF serology or histopathology; 15 patients were included. The number of abnormal foci with restricted diffusion, increased FLAIR signal, intrinsic T1 hyperintensity, abnormal enhancement (CE-T1WI), and intrinsic hyperdensity on CT were recorded., Results: Intralesional susceptibility signal (ISS) foci on SWI were observed in 93.3% of patients with neurotoxoplasmosis (mean size 5.2 ± 3.8 mm). The average number of ISS foci was 3.9 per patient; 3/15 (20.0%) had a single ISS. Amongst other MR sequences, hyperintense FLAIR foci were the most common abnormalities observed (12.4 lesions/patient), followed by enhancing foci (8.2 lesions/patient), foci of restricted diffusion (7.1 lesions/patient), and intrinsic T1 hyperintense foci (3.4 lesions/patient). Abnormalities were least frequently observed on NCCT: abnormalities were identified in 5/15 (33.3%) patients, at a rate of 0.4 lesions/patient., Conclusion: ISS foci are present in the vast majority of neurotoxoplasmosis patients, likely representing hemorrhage. The incidence and frequency of other abnormal foci are highest on FLAIR, and lowest on NCCT.

Over two decades have passed since posterior reversible encephalopathy syndrome (PRES) was first described in 1996. It has becoming increasingly recognised because of improved and more readily available imaging modality. The exact pathophysiological mechanism is not completely understood and remains controversial at present. Precise diagnosis is essential to guide prompt, proper management. Our ability of differentiating it from other acute neurological disorders is likely to improve as we learnt more about the spectrum of this entity in the last 20 years. We emphasise the importance of recognising its diagnostic criteria and biomarker, which would be of great relevance to either outcome evaluation or study design. PRES has a favourable prognosis generally, but neurological sequelae and even fatalities can occur, especially in severe forms that might cause substantial morbidity and even mortality, particularly when the syndrome is complicated by intracranial haemorrhage or brain infarction. In this review, the pathophysiology, approach to diagnosis, some controversies as to the prognosis, as well as the future research direction of PRES are described., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: The lack of fluid-attenuated inversion-recovery (FLAIR) hyperintensity in areas of diffusion-weighted imaging (DWI) high signal, or DWI-FLAIR mismatch, is a potential imaging biomarker for timing of stroke onset. We aimed to determine the effects of DWI infarct lesion volume on DWI-FLAIR mismatch and its accuracy for identification of strokes within intravenous (IV) the thrombolytic therapy window., Methods: Acute ischemic stroke patients with magnetic resonance imaging scan within 12 hours of witnessed stroke were included. Two neuroradiologists independently reviewed DWI and FLAIR sequences for DWI-FLAIR mismatch in areas of restricted diffusion compared to the contralateral normal side., Results: DWI-FLAIR mismatch was identified in 21/82 (26%) patients. Infarct lesions with DWI-FLAIR mismatch were scanned earlier (3.8 ± .3 vs. 7.5 ± .3 hours from onset, P < .001) and were smaller in size (8.9±2.3 vs. 43.1±11.9 mL, P = .007) compared to lesions without mismatch. Multivariate regression analysis showed a significant interaction between lesion volume and time-from-onset in relationship with the presence of DWI-FLAIR mismatch (P = .045). The presence of DWI-FLAIR mismatch had 56% sensitivity, 83% specificity, 48% positive predictive value (PPV), and 87% negative predictive value (NPV) for identification of infarction within 4.5 hours of symptom onset; while for infarct lesions >15 mL, the DWI-FLAIR mismatch had 100% specificity and PPV for acute infarcts within 4.5 hours of onset., Conclusion: The effects of stroke onset-to-scan time gap on DWI-FLAIR mismatch are not the same for different DWI lesion volumes. At DWI lesion volumes >15 mL, the DWI-FLAIR mismatch is highly specific for acute infarcts within IV thrombolytic therapy time, and can identify wake-up stroke patients eligible for treatment., (Copyright © 2016 by the American Society of Neuroimaging.)

Background Recent studies have suggested a correlation between susceptibility-diffusion mismatch and perfusion-diffusion mismatch in acute ischemic stroke patients. Purpose To determine the clinical and imaging associations of susceptibility-diffusion mismatch in patients with acute ischemic stroke in the middle cerebral artery (MCA) territory. Material and Methods Consecutive patients with MCA territory acute ischemic stroke, who had magnetic resonance imaging (MRI) performed with susceptibility-weighted imaging (SWI) and diffusion-weighted imaging (DWI) within 24 h of symptom onset or time last-seen-well, were included. Two neuroradiologists reviewed SWI scans for SWI-DWI mismatch defined by regionally increased vessel number or diameter on SWI extending beyond the DWI hyperintensity territory in the affected hemisphere. The stroke severity at admission was evaluated using the National Institutes of Health Stroke Scale (NIHSS) score. Poor clinical outcome was defined by a 3-month modified Rankin Scale (mRS) score >2. Results The SWI-DWI mismatch was identified in 44 (29.3%) of 150 patients included in this study. Patients with SWI-DWI mismatch had smaller admission infarct volumes (31.2 ± 44.7 versus 55.9 ± 117.7 mL, P = 0.045) and were younger (60.4 ± 18.9 versus 67.1 ± 15.5, P = 0.026). After correction for age, admission NIHSS score, and infarct volume, the SWI-DWI mismatch was associated with a 22.6% lower rate of poor clinical outcome using propensity score matching ( P = 0.032). In our cohort, thrombolytic therapy showed no significant effect on outcome. Conclusion The presence of SWI-DWI mismatch in acute MCA territory ischemic infarct is associated with smaller infarct volume. Moreover, SWI-DWI mismatch was associated with better outcome after correction for infarct size, severity of admission symptoms, and age.

Background: Previous studies have demonstrated inconsistent neurophysiologic effects of ketamine, although discrepant findings might relate to differences in doses studied, brain regions analyzed, coadministration of other anesthetic medications, and resolution of the electroencephalograph. The objective of this study was to characterize the dose-dependent effects of ketamine on cortical oscillations and functional connectivity., Methods: Ten healthy human volunteers were recruited for study participation. The data were recorded using a 128-channel electroencephalograph during baseline consciousness, subanesthetic dosing (0.5 mg/kg over 40 min), anesthetic dosing (1.5 mg/kg bolus), and recovery. No other sedative or anesthetic medications were administered. Spectrograms, topomaps, and functional connectivity (weighted and directed phase lag index) were computed and analyzed., Results: Frontal theta bandwidth power increased most dramatically during ketamine anesthesia (mean power ± SD, 4.25 ± 1.90 dB) compared to the baseline (0.64 ± 0.28 dB), subanesthetic (0.60 ± 0.30 dB), and recovery (0.68 ± 0.41 dB) states; P < 0.001. Gamma power also increased during ketamine anesthesia. Weighted phase lag index demonstrated theta phase locking within anterior regions (0.2349 ± 0.1170, P < 0.001) and between anterior and posterior regions (0.2159 ± 0.1538, P < 0.01) during ketamine anesthesia. Alpha power gradually decreased with subanesthetic ketamine, and anterior-to-posterior directed connectivity was maximally reduced (0.0282 ± 0.0772) during ketamine anesthesia compared to all other states (P < 0.05)., Conclusions: Ketamine anesthesia correlates most clearly with distinct changes in the theta bandwidth, including increased power and functional connectivity. Anterior-to-posterior connectivity in the alpha bandwidth becomes maximally depressed with anesthetic ketamine administration, suggesting a dose-dependent effect.

Purpose: Patients with prior allergic reactions to iodinated contrast require premedication. This study aimed to increase the homogeneity of premedication orders in such patients., Methods: A point-of-care (POC) clinical decision support (CDS) alert accompanied by an order set was implemented in the electronic health record (EHR) to notify providers of a prior allergic reaction upon ordering an examination involving iodinated contrast. Premedication regimens were retrospectively compared 11 months pre- and 11 months post-alert implementation, with the different regimens being classified as follows: (1) "preferred" (per ACR recommendations), (2) "nonpreferred" (corticosteroid administered <24 hours before examination, but not per ACR recommendations), or (3) "no premedication.", Results: Over 22 months, 22,023 iodinated contrast examinations were performed, 200 (186 intravascular, 12 gastrointestinal/genitourinary, 1 intraarticular, 1 intrathecal) being in patients with a documented iodinated contrast allergy (106 pre-, 94 post-alert deployment). Prealert, 41 of 106 patients (38.7%) received a preferred regimen, 47 (44.3%) received nonpreferred regimens, and 18 (17.0%) received no premedication. Postalert, 58 of 94 patients (61.7%) received a preferred regimen, 21 (22.3%) nonpreferred regimens, and 15 (16.0%) no premedication. After alert initiation, the patients prescribed a preferred regimen significantly increased (Z-score = 3.25, P = .001), but there was no significant difference in the proportion of patients with no premedication (Z-score = -0.02, P = .85). In 2 of 200 patients (1.0%), an allergic reaction occurred, both after POC-CDS alert implementation with a preferred regimen administered., Conclusions: The homogeneity of premedication regimens significantly increased after the alert's launch. However, the proportion of patients with no premedication did not significantly change., (Copyright © 2016 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Purpose: Minnelide is an experimental antineoplastic agent that is currently the subject of a phase 1 clinical trial for the treatment of pancreatic and gastrointestinal malignancies. In this study, we documented two cases of reversible acute cerebellar toxicity (REACT) associated with Minnelide and compared its radiological manifestations with other cerebellotoxic agents., Methods: Both patients had histories of progressive metastatic cancer and participated in a phase 1 clinical trial with Minnelide. They had an MRI examination including T2WI, FLAIR and SWI, axial and coronal DWI, and ADC map on admission and follow up., Results: In each patient, the initial MRI demonstrated increased signal on FLAIR and restricted diffusion in the cerebellar cortex without involvement of deep cerebellar nuclei or supratentorial areas. The presenting symptoms and the majority of imaging findings resolved on follow up MRI., Conclusion: To our knowledge, Minnelide has shown an uncommon radiologic pattern of isolated cerebellar cortical involvement compared to other causes of cerebellar toxicity. Since this is a new medication, physicians' familiarity with the presenting symptoms and its temporal association with the imaging findings is important.

Background and Purpose: Evaluating chronic sequelae of optic neuritis, such as optic neuropathy with or without optic nerve atrophy, can be challenging on whole brain MRI. This study evaluated the utility of dedicated coronal contrast-enhanced fat-suppressed FLAIR (CE-FS-FLAIR) MR imaging to detect optic neuropathy and optic nerve atrophy., Materials and Methods: Over 4.5 years, a 3 mm coronal CE-FS-FLAIR sequence at 1.5T was added to the routine brain MRIs of 124 consecutive patients, 102 of whom had suspected or known demyelinating disease. Retrospective record reviews confirmed that 28 of these 102 had documented onset of optic neuritis >4 weeks prior to the brain MRI. These 28 were compared to the other 22 ("controls") of the 124 patients who lacked a history of demyelinating disease or visual symptoms. Using coronal CE-FS-FLAIR, two neuroradiologists separately graded each optic nerve (n = 50 patients, 100 total nerves) as either negative, equivocal, or positive for optic neuropathy or atrophy. The scoring was later repeated., Results: The mean time from acute optic neuritis onset to MRI was 4.1 ± 4.6 years (range 34 days-17.4 years). Per individual nerve grading, the range of sensitivity, specificity, and accuracy of coronal CE-FS-FLAIR in detecting optic neuropathy was 71.4-77.1%, 93.8-95.4%, and 85.5-89.0%, respectively, with strong interobserver (k = 0.667 - 0.678, p < 0.0001), and intraobserver (k = 0.706 - 0.763, p < 0.0001) agreement. For optic atrophy, interobserver agreement was moderate (k = 0.437 - 0.484, p < 0.0001), while intraobserver agreement was moderate-strong (k = 0.491 - 0.596, p < 0.0001)., Conclusion: Coronal CE-FS-FLAIR is quite specific in detecting optic neuropathy years after the onset of acute optic neuritis, but is less useful in detecting optic nerve atrophy.

Aim: To determine the accuracy of the susceptible vessel sign (SVS) in the detection of arterial occlusion and its clinical implication in acute ischaemic stroke., Materials and Methods: Consecutive ischaemic stroke patients who underwent magnetic resonance imaging (MRI) with susceptibility-weighted imaging (SWI) within 24 hours of symptom onset or time last-seen-well were included. Two independent neuroradiologists reviewed the SWI for evidence of the SVS. Admission stroke severity was determined by the National Institute of Health Stroke Scale (NIHSS) scores, and poor clinical outcome was defined by a 3-months modified Rankin scale (mRS) score >2., Results: The SVS was identified in 26 (12%) of 213 patients with substantial inter-reviewer agreement. The SVS had 99% specificity, 88% negative predictive value (NPV), 51% sensitivity, and 92% positive predictive value (PPV) for detection of acute arterial occlusions. In consecutive stroke patients, the presence of SVS was associated with higher admission NIHSS scores (median 9 versus 3, p<0.001), arterial occlusion (92% versus 12%, p<0.001), larger infarct volume (162±180 ml versus 25±48 ml, p=0.001), and higher rate of poor clinical outcome at 3-months follow-up (58% versus 25%, p=0.001). In the subset of patients with acute arterial occlusion (n=47), the SVS was associated with higher admission NIHSS scores (median of 10 versus 3, p=0.038) and larger infarct volumes (173±184 ml versus 76±112 ml, p=0.034)., Conclusions: The SVS is a highly specific sign of occlusive arterial thrombus, and is associated with larger infarct volume and more severe presentation in a series of consecutive stroke patients, as well as in the subgroup of patients with acute arterial occlusion., (Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Background and Purpose: Rabbit models of intracranial aneurysms are frequently used in pre-clinical settings. This study aimed to demonstrate an alternative, extravascular method for creating elastase-induced aneurysms, and how ligation of the right common carotid arteries (RCCA) can impact flow redistribution into left CCA (LCCA)., Methods: Elastase-induced aneurysms in 18 New Zealand rabbits (4.14 ± 0.314 kg) were created by applying 3-5 U of concentrated elastase solution to the exterior of the right and left CCA roots (RCCA and LCCA). After the induction of the aneurysm, the aneurysm was either kept intact to the rest of the corresponding CCA, severed from the rest of the CCA to allow for a free standing aneurysm, or was anchored to nearby tissue to influence the angle and orientation of the aneurysm with respect to the parent vessel. Ultrasound studies were performed before and after creation of aneurysms to collect blood flow measurements inside the aneurysm pouch and surrounding arteries. Prior to sacrificing the animals, computed tomography angiography studies were performed. Harvested aneurysmal tissues were used for histological analysis., Results: Elastase-induced aneurysms were successfully created by the extravascular approach. Histological studies showed that the biological response was similar to human cerebral aneurysms and previously published elastase-induced rabbit aneurysm models. Ultrasound measurements indicated that after the RCCA was ligated, blood flow significantly increased in the LCCA at one-month follow-up., Conclusion: An alternate method for creating elastase-induced aneurysms has been demonstrated. The novel aspects of our method allow for ligation of one or both common carotid arteries to create a single or bilateral aneurysm with an ability to control the orientation of the induced aneurysm.