Brain Imaging Findings Research Articles

Clinical outcomes of two patients with a novel pathogenic variant in ASNS: response to asparagine supplementation and review of the literature

Asparagine synthetase deficiency (ASNSD, OMIM #615574) is a rare autosomal recessive neurometabolic inborn error that leads to severe cognitive impairment. It manifests with microcephaly, intractable seizures, and progressive cerebral atrophy. Currently, there is no established treatment for this condition. In our pediatric cohort, we discovered, by whole-exome sequencing in two siblings from Turkey, a novel homozygous missense mutation in asparagine synthetase at NM_133436.3 (ASNS_v001): c.1108C>T that results in an amino acid exchange p.(Leu370Phe), in the C-terminal domain. After identification of the metabolic defect, treatment with oral asparagine supplementation was attempted in both patients for 24 months. Asparagine supplementation was well tolerated, and no further disease progression was observed during treatment. One of our patients showed mild developmental progress with increased levels of attention and improved nonverbal communication. These results support our hypothesis that asparagine supplementation should be further investigated as a treatment option for ASNSD. We further reviewed all previously reported ASNSD cases with regard for their clinical phenotypes and brain imaging findings to provide an essential knowledge base for rapid diagnosis and future clinical studies.

Epilepsy in Leigh Syndrome With Mitochondrial DNA Mutations.

Background: Leigh syndrome is a mitochondrial cytopathy that presents as a neurodegenerative disease with apparent manifestation in the central nervous system. The aim of the present study was to describe its dominant neurological clinical features and analyze data related to epilepsy in Leigh syndrome accompanied by a mitochondrial DNA mutation.Methods: Whole mitochondrial sequencing was performed on 125 patients clinically suspected of Leigh syndrome. Among them, 25 patients were identified to have mitochondrial DNA associated Leigh syndrome. Electroencephalography (EEG) findings, semiology, brain imaging findings, and biochemical results, were evaluated. We also compared brain magnetic resonance imaging findings and biochemical features in patients with Leigh syndrome based on the presence of epilepsy.Results: Clinical seizures were observed in 14 out of 25 enrolled patients (56%), with focal seizures being the most common type (6/14, 42.8%). All patients were found to have slow and disorganized background neural activity while eight exhibited epileptic discharges on EEG. Mutations at base pairs 10,191 and 8,993 were revealed in a relatively larger number of patients of Leigh syndrome with epilepsy. The presence of gastrointestinal symptoms was significantly more frequent in the epilepsy group (P = 0.042). Diffuse cerebral atrophy was significantly increased (P = 0.042) and cortex signal abnormalities were also increased (P = 0.033) in the epilepsy group.Conclusions: Patients with Leigh syndrome and mitochondrial DNA mutations had a high proportion of central nervous system comorbidities, though the prevalence of epilepsy in this population was not particularly high. Various types of seizure and EEG findings are common in those with Leigh syndrome. Future imaging studies involving more patients and proper mitochondrial DNA mutation analyses are needed to further evaluate the natural course of Leigh syndrome with epilepsy.

The spectrum of neuroimaging findings in febrile infection-related epilepsy syndrome (FIRES): A literature review.

Febrile infection-related epilepsy syndrome (FIRES) is a rare severe epileptic syndrome occurring in previously healthy children and characterized by refractory status epilepticus (SE) following a febrile illness. Brain imaging findings in affected patients have been reported in few case series and some case reports. This article is a comprehensive review of the magnetic resonance imaging (MRI) characteristics in all reported patients with a diagnosis of FIRES, describing the findings in the acute and chronic phases of the disease, and discussing possible pathogenesis and radiologic differential diagnoses. Most of the patients had normal brain scans in the acute phase (61%) and about 25% of the patients reported in literature had abnormalities in the temporal lobes. Changes in the basal ganglia and rarely in thalami or brainstem have also been described, as well as diffuse cerebral edema in a minority of patients during the acute phase. The chronic phase of the disease was characterized by atrophic changes and evidence of mesiotemporal sclerosis. An understanding of these MRI abnormalities is necessary to support the diagnosis of FIRES and exclude mimics.

Abstract TP413: Prediction of Dysphagia Using the Alberta Stroke Program Early CT Score

Background: Dysphagia is common in patients with acute middle cerebral artery (MCA) stroke, and associated with malnutrition, pneumonia and mortality. Hence, identification of patients with swallowing disorder early after stroke onset is important. Besides bedside screening tools, brain imaging findings including lesion size and location may be of value. We investigated whether The Alberta stroke program early CT score (ASPECTS) can be used to predict dysphagia, and whether differences exist herein between the left and the right hemisphere. Methods: The analysis was based on a prospective dataset of 113 patients with acute ischemic stroke in the MCA territory. Fiberoptic endoscopic evaluation of swallowing (FEES) was performed within 24 h after admission for validation of dysphagia. Brain imaging (CT or MRI) was rated for ischemic changes according to the ASPECT score. Results: 62 patients (54.9%) had FEES-proven dysphagia. In left hemispheric strokes the strongest associations between the ASPECTS sectors and dysphagia were found for the lentiform nucleus (ExpB 0.113 [CI 0.028-0.433; p=0.001), the insula (0.275 [0.102-0.742]; p=0.011) and the frontal operculum (0.280 [CI 0.094-0.834]; p=0.022). For right hemispheric strokes, only non-significant associations were found which were strongest for the insula region (0.385 [0.107-1.384]; p=0.144). For the left hemisphere multivariate logistic regression analysis revealed lower ASPECT scores to be independently associated with dysphagia, whereas for the right hemisphere this association was not present. Conclusion: The distribution and extent of early ischemic changes in brain imaging according to ASPECTS allows a reliable prediction of dysphagia in MCA-stroke patients, particularly for the left hemisphere.

Abstract #146: Stimulation of the Prefrontal Cortex Reduces Intentions to Commit Aggression: A Randomized Clinical Trial

Introduction: Although prefrontal brain impairments are one of the best-replicated brain imaging findings in relation to aggression, little is known about the causal role of this brain region. This study tests whether stimulating the dorsolateral prefrontal cortex (DLPFC) using transcranial direct current stimulation (tDCS) reduces the likelihood of engaging in aggressive acts, and the mechanism underlying this relationship.

Varying Patterns of CNS Imaging in InfluenzaA Encephalopathy in Childhood.

The brain imaging findings in children with neurological complications associated with influenza Ainfections are presented and analyzed and pathological imaging changes including atypical intracerebral hemorrhages in these patients are discussed. Neuroimaging findings in six children with influenza encephalopathy following influenza Ainfection between 2012-2017 were retrospectively investigated. Of these five underwent magnetic resonance imaging (MRI) and one computed tomography (CT). Gene analysis was performed in two cases with acute necrotizing encephalitis of childhood (ANEC). The MRI findings of one child were concordant with mild encephalopathy with areversible splenial lesion (MERS); this patient recovered but remained aphasic. In two cases MRI showed typical bilateral thalamic lesions as afeature of ANEC; genetic testing facilitated the diagnosis in one case. One of the patients died, the other showed little improvement. The remaining three patients had multiple diffuse cerebral hemorrhages predominantly affecting the supratentorial white matter after influenza Ainfection complicated by pneumonia, rhabdomyolysis and sepsis requiring extracorporeal membrane oxygenation (ECMO). Neurological complications in children associated with influenza Ainfection may include MERS and ANEC. Additionally, atypical disseminated intracerebral hemorrhages as a complication of influenza Ainfection is reported.

The Tight Medial and High Convexity Subarachnoid Spaces Is the First Finding of Idiopathic Normal Pressure Hydrocephalus at the Preclinical Stage.

Disproportionately enlarged subarachnoid-space hydrocephalus (DESH) findings are often reported as characteristic radiological features of idiopathic normal pressure hydrocephalus (iNPH). However, the process of development of DESH remains unclear. The aim of the present study was to determine the dynamic deforming process and pathophysiology of iNPH. All patients >50 years of age who underwent whole body FDG-PET/CT scanning at Kindai University Hospital between May 2017 and April 2018 were included in this retrospective study, and their brain image findings and clinical information were assessed. We defined DESH-like findings, which had one or two equivocal features of the three components of DESH findings, as preclinical morphologic features of DESH (PMD). PMD were classified into six subtypes based on their component of DESH findings: PMD-T, only tight medial and high convexity subarachnoid spaces (TMC); PMD-S, only enlarged Sylvian fissures; PMD-V, only ventriculomegaly; PMD-TV, TMC and ventriculomegaly; PMD-TS, TMC and enlarged Sylvian fissures; PMD-SV, enlarged Sylvian fissures and ventriculomegaly. A total of 2196 cases (70.5 ± 9.3 years) were enrolled, with 54 cases (77.1 ± 5.9 years) with DESH findings, and 42 cases (72.9 ± 7.9 years) with PMD (five PMD-T, two PMD-V, 12 PMD-TV, 18 PMD-TS, and five PMD-SV). In each component of DESH, 35 of 42 (83.3%) cases with PMD had TMC. We suggest that the TMC is the first change on DESH findings in most iNPH cases, and may be an important part of the pathophysiology of iNPH.

SA93 - IMAGING GENETICS TOWARDS A NEW DIAGNOSIS OF SCHIZOPHRENIA

Background Current diagnoses of Schizophrenia (SZ) and related psychiatric disorders are catalogued by phenomenological principles and clinical descriptions. Complicated gene and environmental factor interactions likely play an important role in the onset of SZ and induce great heterogeneity. This unclear etiology and heterogeneity prevent the establishing of accurate subgroups within SZ through clinical observation alone; simultaneously, the boundaries among psychiatric disorders previously drawn by phenomenological findings are merging because there is great overlap, especially in genetic variations and brain imaging findings. By characterizing and quantifying brain regions affected in psychiatric disorders, imaging genetics is a valuable research method to fulfill a new diagnostic system. We review contributions of imaging genetics to SZ diagnosis, limitations, and possible future directions. Methods Among numerous imaging genetic studies, we reviewed recent studies with relatively clear and consistent findings. They were either done in task-phase imaging to indicate certain cognitive impairments of SZ, or the genes included were highlighted in SZ itself or an important cognitive domain related to SZ. Results Some pioneering studies contribute to subtypes and disorder boundaries. The clustering study from Arnedo et al. formed correlations between disjoined networks of symptom groups and Single Nucleotide Polymorphism (SNP) sets, and it may be promising for future SZ subtypes. Bipolar-SZ Network on Intermediate Phenotypes studies combining various clinical biomarkers and brain imaging divided SZ, bipolar disorder and schizoaffective disorder into three different “biotypes” regardless original diagnoses, and it provided meaningful insight into the disorder boundaries. For imaging genetics research, large numbers of associations between functional imaging intermediate phenotypes and genes have been found in working memory, episodic memory, emotion, attention, cognitive control, and theory of mind in SZ or healthy risk allele carriers. Such associations were difficult to identify while using structural brains measures. Discussion Imaging genetics will continue to shape the diagnosis of SZ and related disorders. However, there are still problems to solve. Most importantly, the logic behind imaging genetics has been questioned. Franke et al. reminds us the structural brain deficits believed to be important pathological alterations of SZ may reflect prenatal and later development environmental effects not specific to SZ, or the diagnostic category of SZ may not be uniformly organized. The following aspects need future effort. Firstly, more brain measures need to be introduced, and the criteria of intermediate phenotypes should be carefully checked. The specificity of brain alterations will need careful examination in clinical settings. Secondly, more genetic factors need to be collected. Polygenic risk scores, parallel independent component analysis and other clustering method may be promising. Factors other than SNPs, such as copy number variations and regulatory factors will need to be included. Finally, imaging genetics will need compatible phenomenological assessment scales which need not distinguish current diagnoses but provide a comprehensive scan of clinical features.

Neurodevelopmental Outcome of Severe Acidemic Term Infants

Objective: This study aimed to evaluate the perinatal factors associated with neonatal mortality and neurologic morbidity in term infants with severe acidosis. Methods: We retrospectively reviewed the data of term infants with severe acidosis from January 2012 to December 2016. Severe acidosis was defined as initial pH of less than <7.0 and base excess ≥-12 mmol/L. We searched the clinical characteristics, morbidities of mother and infants, and neuroimaging results. Also infants were divided by neurodevelopmental impairment and evaluated the relating perinatal factors. Results: Twenty three term infants had severe acidosis. Meconium stained amniotic fluid was found in 43.5% and neonatal resuscitation with positive pressure ventilation and endotracheal intubation was needed in 43.5% and 26.1%. Among 8 infants with hypoxic-ischemic encephalopathy (HIE), stage 2 or higher were 87.5%. Four infants (17.4%) showed abnormal brain imaging taken before discharge. On the analysis, the longer duration of invasive mechanical ventilation (P=0.049) and increased need for gavage feeding (P=0.021) were found in neurodevelopment impairment group. Conclusion: The presence of HIE and abnormal findings of brain imaging before discharge were found to be associated with abnormal neurodevelopmental outcome in term infants with severe acidosis. Even if the brain imaging test was normal, we should consider the long-term follow-up of severe acidemic term infants.

Pain-related behavior and brain activation in cynomolgus macaques with naturally occurring endometriosis.

Can pain be objectively assessed in macaques with naturally occurring endometriosis? Behavioral, pharmacological and in vivo brain imaging findings indicate that pain can be quantified in macaques with endometriosis. Endometriosis is characterized by abdominopelvic hypersensitity. The mechanism by which endometriosis evokes pain is largely unknown, as currently available analgesics offer limited pain relief. Thus, there is a need for both greater understanding of the in vivo mechanism of endometriosis-associated pain and better methods of testing novel therapeutics. Pain-related behavior and brain activation were assessed in five cynomolgus macaques with endometriosis. Three healthy female macaques served as controls. Abdominopelvic sensitivity to force was assessed with an algometer. Activation of brain areas using block design force stimulation and the effects of a single dose of the analgesic drug morphine and 2-month treatment with the progestin dienogest on brain activation were observed via functional magnetic resonance imaging. Pain response thresholds in macaques with endometriosis were significantly less than that of healthy macaques (P = 0.0003). In addition, non-noxious force activated the insula and thalamus, which was reduced with morphine and 2-month dienogest treatment. The specific role of cysts, such as peritoneal cysts, in endometriosis pain was not explored. While non-noxious stimulation activated the insula and thalamus, macaques were sedated during fMRI scans. Current findings need further confirmation in a larger cohort. The current study demonstrated central sensitization and related pain behavior in macaques with naturally occurring endometriosis. Altered functioning of the central nervous system could be the focus of future mechanistic studies and for the development of novel therapeutics. Supported by a grant from the Shizuoka Industrial Foundation. All authors are employees of Hamamatsu Pharma Research, Inc.

HERPES SIMPLEX VIRUS ENCEPHALITIS IN AN 8 YEARS OLD WITH NORMAL CEREBROSPINAL FLUID AND NEGATIVE HERPES SIMPLEX VIRUS POLYMERASE CHAIN REACTION - A CLINICAL AND RADIOLOGICAL DIAGNOSIS

Herpes simplex encephalitis is known to cause significant morbidity and mortality both in children and adults. Polymerase chain reaction (PCR) for herpes simplex virus (HSV) in cerebrospinal fluid (CSF) is the diagnostic modality accepted worldwide. However, a negative CSF HSV PCR result should always be interpreted in the context of the timing of specimen collection and also considering the clinical picture. We report a case of HSV encephalitis in an 8-year-old male child whose initial CSF picture was normal and CSF for HSV PCR was also negative. However, the magnetic resonance imaging brain findings and clinical profile along with a marked response to acyclovir therapy started very early in the course of illness left little doubts about the diagnosis.

Imaging findings after acute sport-related concussion in American football players: A systematic review

Sport-related concussion (SRC) has emerged as a major public health problem. The results of brain imaging studies following SRC have raised questions about long-term neurologic health, but the clinical implications of these findings remain unknown. A systematic review of brain imaging findings after SRC was performed utilizing the following inclusion criteria: football players, brain imaging within 6 months of SRC, and sample size >5. Studies were assessed for: 1) methodology, 2) imaging outcomes, and 3) number of positive statistical comparisons. Imaging was classified as immediate (≤1 week post-injury) or subacute (>1 week to 6 months post-injury). Eleven studies met inclusion criteria. Eight of the 11 studies conducted a total of 809 comparisons of brain function, of which 149 (18%) were statistically significant. Nine of the 11 studies (82%) reported positive immediate findings, but were more likely to be subject to recall bias (86% vs. 0%) and to lack baseline advanced brain imaging (78% vs. 50%) than negative studies. Only 3 of 9 studies that reported subacute findings (33%) reported positive results, and these positive studies were also more likely to be subject to recall bias (100% vs. 40%) and to lack baseline advanced brain imaging (100% vs. 67%) than negative studies. The results of the study demonstrate the transitory nature of positive imaging findings and methodological limitations that complicate study interpretation. Further research is required to correlate imaging findings with clinical outcomes.

Cognitive-Motor Interference in Neurodegenerative Disease: A Narrative Review and Implications for Clinical Management.

This paper provides a narrative review of cognitive motor interference in neurodegeneration, including brain imaging findings specific to interference effects in neurodegenerative disease, and dual task assessment and intervention in Parkinson’s disease (PD), multiple sclerosis (MS), and Huntington’s disease (HD). In a healthy central nervous system the ability to process information is limited. Limitations in capacity to select and attend to inputs influence the ability to prepare and perform multiple tasks. As a result, the system balances demands, switching attention to the most task-relevant information as it becomes available. Limitations may become more apparent in persons with neurodegenerative diseases (ND) with system-specific impairments in PD, MS, and HD. These ND affect both cognitive and motor function and are thus particularly susceptible to dual task interference. Issues related to performer and task characteristics and implications of these findings for both the standard assessment of dual task abilities as well as development and evaluation of interventions aimed at improving dual task ability are discussed. In addition, we address the need for optimizing individualized assessment, intervention and evaluation of dual task function by choosing cognitive and motor tasks and measures that are sensitive to and appropriate for the individual’s level of function. Finally, we use current evidence to outline a 5-step process of clinical decision making that uses the dual task taxonomy as a framework for assessment and intervention.

Cerebrovascular Injury Following Scorpion Sting and Snake Envenomation: A Case Series.

Neurological complications following snake and scorpion bite are diverse. Literature regarding patterns of cerebrovascular injury (CVI) and outcomes among these patients is scarce. This is a descriptive study of the clinical profile, brain imaging findings, mechanisms of injury, vascular territory involvement and outcomes of CVI following scorpion and snake envenomation, in a tertiary care center in South India.MethodologyPatients with scorpion sting- and snake envenomation-related complications were retrospectively enrolled. Neuroimaging was performed on five patients with each envenomation, and they were found to have neurological involvement. On imaging, three patients were found to have a CVI. Clinical, radiological parameters and outcomes of these patients were studied. We also performed a review of the literature and analyzed the finding of all the cases.ResultIn all, three patients each had evidence of CVI in imaging. An additional 32 reports of scorpion sting-related CVI and 35 reports of snake envenomation-related CVI were identified from the literature. There was a male predominance among these patients. Mean age of the patients with scorpion sting was 42.8 years as compared with 33 years for the patients with snake envenomation. Features of severe envenomation were present in all patients. Persistently depressed sensorium and new-onset focal neurological deficits were seen in 70% of all patients. Infarcts were seen in 88% of patients with snake envenomation and 53% of patients with a scorpion sting. Mortality was 28% among patients with a scorpion sting as compared with 8% with snake envenomation. Cerebrovascular injuries are uncommon neurological manifestations following scorpion and snake envenomation. These tend to occur in younger patients. Infarcts are more common than bleeds.

Cardiac Myxoma and Cerebrovascular Events: A Retrospective Cohort Study.

Background: Cardiac myxoma (CM) is the most frequent, cardiac benign tumor and is associated with enhanced risk for cerebrovascular events (CVE). Although surgical CM excision is the only curative treatment to prevent CVE recurrence, in recent reports conservative treatment with antiplatelet or anticoagulant agents in high-risk patients with CM-related CVE has been discussed.Methods: Case records at the University Hospital of Tübingen between 2005 and 2017 were screened to identify patients with CM-related CVE. Clinical features, brain and cardiac imaging findings, histological reports, applied treatments and long-term neurological outcomes were assessed.Results: 52 patients with CM were identified and among them, 13 patients with transient ischemic attack, ischemic stroke or retinal ischemia were included to the (to our knowledge) largest reported retrospective study of CM-related CVE. In all identified patients, CVE was the first manifestation of CM; 61% suffered ischemic stroke, 23% transient ischemic attack and 15% retinal ischemia. In 46% of the patients, CVE occurred under antiplatelet or anticoagulation treatment, while 23% of the patients developed recurrent CVE under bridging-antithrombotic-therapy prior to CM surgical excision. Prolonged time interval between CVE and CM-surgery was significantly associated with CVE recurrence (p = 0.021). One patient underwent i.v. thrombolysis, followed by thrombectomy, with good post-interventional outcome and no signs of hemorrhagic transformation.Discussion: Our results suggest that antiplatelet or anticoagulation treatment is no alternative to cardiac surgery in patients presenting with CM-related CVE. We found significantly prolonged time-intervals between CVE and CM surgery in patients with recurrent CVE. Therefore, we suggest that the waiting- or bridging-interval with antithrombotic therapy until curative CM excision should be kept as short as possible. Based on our data and review of the literature, we suggest that in patients with CM-related CVE, i.v. thrombolysis and/or endovascular interventions may present safe and efficacious acute treatments.

Neurologic challenges in 22q11.2 deletion syndrome.

Children with 22q11.2 deletion syndrome often come to medical attention due to signs and symptoms of neurologic dysfunction. It is imperative to understand the expected neurologic development of patients with this diagnosis in order to be alert for the potential neurologic complications, including cortical malformations, tethered cord, epilepsy, and movement disorders. We present an update of brain imaging findings from the CHOP 22q and You Center, a review of the current literature, and our current management practices for neurological issues.

Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia: An MRI Study of 16 French Cases.

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia is an autosomal dominant leukoencephalopathy related to CSF1R gene mutations. A growing number of clinicoradiologic phenotypes have been described. In this study, we analyzed brain imaging findings in 16 patients with adult-onset leukoencephalopathy with axonal spheroids and pigmented glia to refine radiologic diagnostic clues. T2/FLAIR white matter hyperintensities were present in all patients with frontal or frontoparietal predilection, with asymmetric distribution in more than one-third. Brain atrophy and callosal involvement were almost constant, and corticospinal tract involvement was frequent. Moreover, deep white matter hyperintense dots on DWI and deep punctate calcifications on CT were often found. Conversely, deep gray matter nuclei, external capsules, and brain stem were rarely involved. Our series emphasized the great variability of MR imaging findings seen in adult-onset leukoencephalopathy with axonal spheroids and pigmented glia. A complete imaging screening including DWI, T2*, and CT is mandatory to accurately assess patients with suspected inherited adult-onset leukoencephalopathy.

Extrapyramidal deficits in ALS: a combined biomechanical and neuroimaging study.

Extrapyramidal deficits are poorly characterised in amyotrophic lateral sclerosis (ALS) despite their contribution to functional disability, increased fall risk and their quality-of-life implications. Given the concomitant pyramidal and cerebellar degeneration in ALS, the clinical assessment of extrapyramidal features is particularly challenging. The comprehensive characterisationof postural instability in ALS using standardised clinical assessments, gait analyses and computational neuroimaging tools in a prospective study design. Parameters of gait initiation in the anticipatory postural adjustment phase (APA) and execution phase (EP) were evaluated in ALS patients with and without postural instability and healthy controls. Clinical and gait analysis parameters were interpreted in the context of brain imaging findings. ALS patients with postural instability exhibit impaired gait initiation with an altered APA phase, poor dynamic postural control and significantly decreased braking index. Consistent with their clinical profile, "unsteady" ALS patients have reduced caudate and brain stem volumes compared to "steady" ALS patients. Our findings highlight that the ALS functional rating scale (ALSFRS-r) does not account for extrapyramidal deficits, which are major contributors to gait impairment in a subset of ALS patients. Basal ganglia degeneration in ALS does not only contribute to cognitive and behavioural deficits, but also adds to the heterogeneity of motor disability.

Stimulation of the Prefrontal Cortex Reduces Intentions to Commit Aggression: A Randomized, Double-Blind, Placebo-Controlled, Stratified, Parallel-Group Trial.

Although prefrontal brain impairments are one of the best-replicated brain imaging findings in relation to aggression, little is known about the causal role of this brain region. This study tests whether stimulating the dorsolateral prefrontal cortex using transcranial direct current stimulation (tDCS) reduces the likelihood of engaging in aggressive acts, and the mechanism underlying this relationship. In a double-blind, stratified, placebo-controlled, parallel-group, randomized trial, 81 human adults (36 males, 45 females) were randomly assigned to an active (N = 39) or placebo (N = 42) condition, and then followed up 1 d after the experiment session. Intentions to commit aggressive acts and behavioral aggression were assessed using hypothetical vignettes and a behavioral task, respectively. The secondary outcome was the perception of the moral wrongfulness of the aggressive acts. Compared with the sham controls, participants who received anodal stimulation reported being less likely to commit physical and sexual assault (p < 0.01). They also judged aggressive acts as more morally wrong (p < 0.05). Perceptions of greater moral wrongfulness regarding the aggressive acts accounted for 31% of the total effect of tDCS on intentions to commit aggression. Results provide experimental evidence that increasing activity in the prefrontal cortex can reduce intentions to commit aggression and enhance perceptions of the moral wrongfulness of the aggressive acts. Findings shed light on the biological underpinnings of aggression and theoretically have the potential to inform future interventions for aggression and violence.SIGNIFICANCE STATEMENT Aggressive behaviors pose significant public health risks. Understanding the etiology of aggression is paramount to violence reduction. Investigations of the neural basis of aggression have largely supported correlational, rather than causal, interpretations, and the mediating processes underlying the prefrontal-aggression relationship remain to be well elucidated. Through a double-blind, stratified, placebo-controlled, parallel-group, randomized trial, this study tested whether upregulation of the prefrontal cortex reduces the likelihood of engaging in aggression. Results provide experimental evidence that increasing prefrontal cortical activity can reduce intent to commit aggressive acts. They also shed light on moral judgment as one mechanism that may link prefrontal deficits to aggression and, in theory, have the potential to inform future approaches toward reducing aggression.

Brain Imaging Findings and Neurologic Complications after Allogenic Hematopoietic Stem Cell Transplantation in Children.

Hematopoietic stem cell transplantation (HSCT) is the only therapy for a subset of patients with malignant and nonmalignant diseases. Central nervous system (CNS) complications continue to be an important cause of morbidity and significantly contribute to mortality after HSCT. These complications include infections, cerebrovascular lesions, therapy-induced diseases, metabolic disturbances, and post-HSCT carcinogenesis. Following HSCT, three phases can be identified on the basis of the patient's immune status: the pre-engraftment period (<30 days after HSCT), the early postengraftment period (30-100 days after HSCT), and the late postengraftment period (>100 days after HSCT). There is a distinct relationship between the patient's degree of immunodeficiency after HSCT and the incidence of various complications that may occur. Early diagnosis of CNS complications is crucial for successful management and a good prognosis, and computed tomography and magnetic resonance imaging play an important role in achieving these goals. The global increase in the use of HSCT requires radiologists to be familiar with CNS complications, their relationship to the patient's immune status, and their imaging appearances. This article describes the clinical background of HSCT; reviews the incidence, causes, and timeline of brain complications in children who underwent allogenic HSCT; and identifies the characteristic imaging findings of these disorders. ©RSNA, 2018.