Accumbens coordinated reset stimulation in mice exhibits ameliorating aftereffects on binge alcohol drinking

BackgroundAlcohol use disorder (AUD) affects nearly 5% of the world’s adult population. Despite treatment, AUD often manifests with relapse to binge drinking, which has been associated with corticostriatal hypersynchrony involving the nucleus accumbens (NAc).MethodsA modified “Drinking in the Dark” protocol was used to provoke binge-like alcohol drinking. We implemented Coordinated Reset Stimulation (CRS), a computationally designed, spatio-temporal stimulation algorithm, to desynchronize abnormal neuronal activity via a deep brain stimulation (DBS) electrode in the NAc of mice exhibiting binge-like alcohol drinking. Integral CRS charge injected would be 2.5% of that of conventional high-frequency DBS.ResultsNAc CRS delivery during only the initial phase of exposure to alcohol and prior to the exposure (but not during) significantly reduced binge-like drinking without interfering with social behavior or locomotor activity.ConclusionsNAc CRS ameliorates binge-like alcohol drinking and preliminarily exhibits sustained aftereffects that are suggestive of an unlearning of hypersynchrony.     

The impact of obstructive sleep apnea on bronchiolitis severity in children with Down syndrome

ObjectivesAcute bronchiolitis commonly causes respiratory failure in children ≤2 years, and is particularly severe in those with Down syndrome (DS). Obstructive sleep apnea (OSA), common in DS, is also associated with respiratory complications. However, it is unknown whether OSA is associated with worse outcomes in children with and without DS, hospitalized with bronchiolitis. We hypothesized that in children with bronchiolitis, OSA is associated with worse outcomes in those with DS, independent of DS-related comorbidities.MethodsHospital discharge records of children with bronchiolitis aged ≤2 years were obtained for 1997–2012 from the Kid's Inpatient Database. The primary outcome was invasive mechanical ventilation (IMV), and secondary outcomes were non-invasive mechanical ventilation (NIMV), length of hospital stay, and inflation-adjusted cost of hospitalization (IACH). Multivariable regression was conducted to ascertain the associations between OSA and primary and secondary outcomes accounting for DS-associated comorbidities.ResultsThere were 928,961 hospitalizations for bronchiolitis. The DS group with bronchiolitis (n = 8697) was more likely to have OSA [241 (2.77%) vs 1293 (0.14%), p < 0.001] compared to the non-DS group (n = 920,264). Multivariable logistic regression showed that OSA was associated with IMV (adjusted odds ratio [OR], 3.32 [95% CI 2.54–4.35], p < 0.0001) in all children with bronchiolitis; and in those with DS, it was associated with IMV (adjusted OR, 2.34 [95% CI 1.38–3.97], p = 0.002), NIMV (adjusted OR, 8.21 [95% CI 4.48–15.04], p < 0.0001) and IACH (adjusted β, 0.18 [95% CI 0.02–0.34], p = 0.031).ConclusionsOSA is independently associated with assisted ventilation in all children hospitalized with bronchiolitis, regardless of DS-associated comorbidities in those with DS. The severity of bronchiolitis in children with DS may be driven by the high prevalence of OSA.     

Short-term effect of a close-fitting type of walking assistive device on spinal cord reciprocal inhibition

One of the major problems with walking encountered by patients with spastic hemiplegia is diminished toe clearance due to spasticity of their leg muscles. To improve their walking, a specialized robot assist for ankle movements (RE-Gait) has been utilized. The present study examined the neurophysiological effects whether spinal cord reciprocal Ia inhibition (RI) in the leg was altered by using RE-Gait. Sixteen patients with a clinical diagnosis of stroke were divided into the two groups, RE-Gait walking group (Group R) and normal (controlled) walking group (Group C). In each group, they walked on a flat floor for 15 min with or without RE-Gait. The depression of soleus (Sol) H-reflexes conditioned by common peroneal nerve stimuli with the conditioning-test (C-T) intervals of 1, 2, 3, and 4 ms were assessed before and immediately after each walking session. After the intervention, the LSM (SE) of Sol H-reflex amplitude with 1, 2 and 3 ms C-T interval conditions were significantly decreased in group R (1 ms: 88.15 (4.60), 2 ms: 86.37 (4.60), 3 ms: 89.68 (4.62)) compared to group C (1 ms: 105.57 (4.56), 2 ms: 100.89 (4.58), 3 ms: 107.72 (4.58)) [1 ms: p = 0.012, 2 ms: p = 0.035, 3 ms: p = 0.011]. Walking assistive robot that targets ankle movements might be a new rehabilitation tool for regulating spinal cord excitability.     

Review of synthetic MRI in pediatric brains: Basic principle of MR quantification,its features,clinical applications,and limitations

Quantitative magnetic resonance imaging (MRI) with multislice, multi-echo, and multi-delay acquisition enables simultaneous quantification of R₁ and R₂ relaxation rates, proton density, and the B₁ field in a single acquisition, and requires only about 6 minutes for full-head coverage. Using dedicated SyMRI software, radiologists can generate any contrast-weighted image by manipulating the acquisition parameters, including repetition time, echo time, and inversion time. Moreover, automatic brain tissue segmentation, volumetry, and myelin measurement can also be performed. Using the SyMRI approach, a shorter scan time, an objective examination, and personalized MR imaging parameters can be obtained in daily clinical pediatric imaging. Here we summarize and review the use of SyMRI in imaging of the pediatric brain, including the basic principles of MR quantification along with its features, clinical applications, and limitations.     

Decreased resting-state alpha peak frequency in children and adolescents with fetal alcohol spectrum disorders or prenatal alcohol exposure

Prenatal alcohol exposure (PAE) can result in long-lasting changes to physical, behavioral, and cognitive functioning in children. PAE might result in decreased white matter integrity, corticothalamic tract integrity, and alpha cortical oscillations. Previous investigations of alpha oscillations in PAE/fetal alcohol spectrum disorder (FASD) have focused on average spectral power at specific ages; therefore, little is known about alpha peak frequency (APF) or its developmental trajectory making this research novel. Using resting-state MEG data, APF was determined from parietal/occipital regions in participants with PAE/FASD or typically developing controls (TDC). In total, MEG data from 157 infants, children, and adolescents ranging in age from 6 months to 17 years were used, including 17 individuals with PAE, 61 individuals with an FASD and 84 TDC. In line with our hypothesis, we found that individuals with PAE/FASD had significantly reduced APF relative to TDC. Both age and group were significantly related to APF with differences between TDC and PAE/FASD persisting throughout development. We did not find evidence that sex or socioeconomic status had additional impact on APF. Reduced APF in individuals with an FASD/PAE may represent a long-term deficit and demonstrates the detrimental impact prenatal alcohol exposure can have on neurophysiological processes.     

Evaluation of frequency-selective non-linear blending technique on brain CT in postoperative children with Moyamoya disease

ObjectiveTo evaluate whether a frequency-selective non-linear blending (BC) technique can improve tissue contrast and infarct detection on non-enhanced brain CT (NECT) in postoperative Moyamoya (MMD) patients.Materials and methodsFrom January 2010 to December 2017, 33 children (13 boys and 20 girls; mean age 9.1 ± 3.4 years) with MMD postoperatively underwent NECT followed by diffusion MRI. We compared the contrast-to-noise ratio (CNR) between gray matter (GM) and white matter (WM) in NECT and BC images and the CNR between the infarct lesion and adjacent normal-appearing brain in NECT and BC images using a paired t-test. We assessed image noise, GM-WM differentiation, artifacts, and overall quality using a Wilcoxon signed rank test. A McNemar two-tailed test was conducted to compare the diagnostic accuracy of infarct detection.ResultsThe CNR between GM and WM and the CNR of the infarct was better in BC images than in NECT images (3.9 ± 1.0 vs. 1.8 ± 0.6, P < 0.001 and 3.6 ± 0.3 vs. 1.9 ± 0.2, P < 0.001), with no difference in overall image quality observed. The sensitivity and specificity of infarct detection were 55.0% and 76.9% using NECT, and 70.0% and 69.2% using BC technique. The diagnostic accuracy of NECT and BC technique was 63.6% (21/33) and 69.7% (23/33), respectively.ConclusionThis study showed that the BC technique improved CNR and maintained image quality. This technique may also be used to identify ischemic brain changes in postoperative MMD patients by improving the CNR of the infarct lesion.     

Influence of inferior petrosal sinus drainage symmetry on detection of adenomas in Cushing's syndrome

BackgroundAsymmetric inferior petrosal sinuses (IPS) are not infrequently encountered during bilateral IPS sampling. There is little data on whether IPS symmetry influences success in predicting the adenoma side in patients with ACTH-dependent Cushing's syndrome (CS).ObjectiveTo assess the influence of IPS drainage patterns on detection of an adenoma in CS.MethodsRetrospective single-center cohort analysis reviewing records of patients with CS and negative MRI findings who subsequently underwent BIPSS.ResultsBIPSS was performed in 38 patients with a mean age of 45 ± 15 years. The overall technical success rate was 97% for bilateral cannulation. Asymmetric IPS were observed in 11 (39%) patients with Cushing's disease (CD). A side-to-side ACTH ratio was not significantly different between patients with symmetric outflow and those with asymmetric outflow at baseline (8.6 ± 2.7 versus 16.4 ± 6.0; P = 0.45), but ratios were significantly different after ovine corticotropin-releasing hormone (oCRH) stimulation (6.0 ± 2.5 versus 35.7 ± 22.5; P = 0.03). BIPSS correctly predicted the side of the adenoma in 25 (96%) patients with CD. Prediction was better when the venous outflow was symmetric (100%) rather than asymmetric (93%), although the difference was not significant (P = 0.42). Remission from CS was achieved in 32 patients (87%), independent of the symmetry of IPS.ConclusionsBearing in mind the sample size of this audit, asymmetric IPS at least do not seem to diminish the accuracy of diagnosis of ACTH-dependent CS, nor do they influence the clinical outcome.     

Consensus Guidelines of the French Society of Neuroradiology (SFNR) on the use of Gadolinium-Based Contrast agents (GBCAs) and related MRI protocols in Neuroradiology

Gadolinium-based contrast agents (GBCAs) are used in up to 35% of magnetic resonance imaging (MRI) examinations and are associated with an excellent safety profile. Nevertheless, two main issues have arisen in the last two decades: the risk of nephrogenic systemic fibrosis and the risk of gadolinium deposition and retention. As a first step, this article reviews the different categories of GBCAs available in neuroradiology, their issues, and provides updates regarding the use of these agents in routine daily practice. Recent advances in MRI technology, as well as the development of new MRI sequences, have made GBCA injection avoidable in many indications, especially in patients with chronic diseases when iterative MRIs are required and when essential diagnostic information can be obtained without contrast enhancement. These recent advances also lead to changes in recommended MRI protocols. Thus, in a second step, this review focuses on consensus concerning brain MRI protocols in 10 common situations (acute ischemic stroke, intracerebral hemorrhage, cerebral venous thrombosis, multiple sclerosis, chronic headache, intracranial infection, intra- and extra-axial brain tumors, vestibular schwannoma and pituitary adenoma). The latter allowing the standardization of practices in neuroradiology. Recommendations were also made concerning the use of GBCAs in neuroradiology, based on evidence in the literature and/or by consensus between the different coauthors.     

Primary Lateral Sclerosis: Clinical,radiological and molecular features

Primary Lateral Sclerosis (PLS) is an uncommon motor neuron disorder. Despite the well-recognisable constellation of clinical manifestations, the initial diagnosis can be challenging and therapeutic options are currently limited. There have been no recent clinical trials of disease-modifying therapies dedicated to this patient cohort and awareness of recent research developments is limited. The recent consensus diagnostic criteria introduced the category ‘probable’ PLS which is likely to curtail the diagnostic journey of patients. Extra-motor clinical manifestations are increasingly recognised, challenging the view of PLS as a 'pure' upper motor neuron condition. The post mortem literature of PLS has been expanded by seminal TDP-43 reports and recent PLS studies increasingly avail of meticulous genetic profiling. Research in PLS has gained unprecedented momentum in recent years generating novel academic insights, which may have important clinical ramifications.     

Endovascular management of multiple intracranial dural arteriovenous fistulas

Background and purposeMultiply occurring intracranial dural arteriovenous fistulas (dAVFs) have been documented but rarely occur, and neither pathogenesis nor prognosis is clearly understood. This study was conducted to analyze angiographic characteristics of multiple dAVFs and to chronicle our treatment experience.MethodsBetween April, 2002 and January, 2018, data prospectively collected from 310 patients with intracranial dAVFs were systematically reviewed, assessing clinical and anatomic outcomes of endovascular treatment in 32 patients with multiple dAVFs (≥ 2 fistulas each). Lesions were categorized as multifocal or diffuse type, depending on presentation, and further characterized as progressive or non-progressive disease.ResultsOverall, 18 patients (56.3%) experienced aggressive presentations, including intracerebral hemorrhage or venous infarction. Cortical venous reflux (CVR) was observed in 26 patients (81.3%), and sinus thrombosis or occlusion was seen in 24 (75.0%). Clinical outcomes in patients with multifocal fistulas (n = 11) were excellent (100%), marked by a moderately high rate of complete occlusion (54.5%). Those with progressive disease (n = 10) regularly displayed certain angiographic findings, namely diffuse configuration (100%), sinus thrombosis (100%), and CVR (100%). Complete anatomic obliteration was achieved in 12 patients (37.5%), and in 26 patients (81.3%), clinical outcomes were favorable.ConclusionMultiple dAVFs are typically aggressive at presentation, given strong associations with CVR and sinus thrombosis. In diffuse-type fistulas, the potential to recur or progress is high. Although definitive treatment poses a challenge, outcomes of endovascular therapeutics may be still optimized in this setting through strategic procedural modifications and careful follow-up monitoring.     

Improved object recognition memory using post-encoding repetitive transcranial magnetic stimulation

BackgroundBrain stimulation is known to affect canonical pathways and proteins involved in memory. However, there are conflicting results on the ability of brain stimulation to improve to memory, which may be due to variations in timing of stimulation.HypothesisWe hypothesized that repetitive transcranial magnetic stimulation (rTMS) given following a learning task and within the time period before retrieval could help improve memory.MethodsWe implanted male B6129SF2/J mice (n = 32) with a cranial attachment to secure the rTMS coil so that the mice could be given consistent stimulation to the frontal area whilst freely moving. Mice then underwent the object recognition test sampling phase and given treatment +3, +24, +48 h following the test. Treatment consisted of 10 min 10 Hz rTMS stimulation (TMS, n = 10), sham treatment (SHAM, n = 11) or a control group which did not do the behavior test or receive rTMS (CONTROL n = 11). At +72 h mice were tested for their exploration of the novel vs familiar object.ResultsAt 72-h's, only the mice which received rTMS had greater exploration of the novel object than the familiar object. We further show that promoting synaptic GluR2 and maintaining synaptic connections in the perirhinal cortex and hippocampal CA1 are important for this effect. In addition, we found evidence that these changes were linked to CAMKII and CREB pathways in hippocampal neurons.ConclusionBy linking the known biological effects of rTMS to memory pathways we provide evidence that rTMS is effective in improving memory when given during the consolidation and maintenance phases.     

Lateral spread response of different facial muscles during microvascular decompression in hemifacial spasm

ObjectiveInterpreting lateral spread response (LSR) during microvascular decompression (MVD) for hemifacial spasm (HFS) is difficult when LSRs observed in different muscles do not match. We aimed to analyze LSR patterns recorded in both the orbicularis oris (oris) and mentalis muscles and their relationships with clinical outcomes.MethodsThe data of 1288 HFS patients who underwent MVD between 2015 and 2018 were retrospectively reviewed. LSR was recorded in the oris and mentalis muscles through centrifugal stimulation of the temporal branch of the facial nerve after preoperative mapping. The disappearance of LSR following surgery, clinical outcomes, and the characteristics of LSR in oris were analyzed.ResultsAfter surgery, LSR remained in 100 (7.7%) and 279 (21.6%) of the mentalis and oris muscles, respectively. The postoperative outcome correlated with LSR disappearance in the mentalis, not with that in the oris.ConclusionLSR patterns differed in each muscle and may not be correlated with clinical outcomes. LSR in the mentalis and oris muscles should be interpreted differently.SignificanceWe describe a monitoring protocol characterized by preoperative facial nerve mapping, antidromic stimulation, and recording from multiple muscles. We analyze differences in LSRs in the mentalis and oris muscles and suggest technical points for interpretation.     

Long-term impact of prenatal exposure to chemotherapy on executive functioning: An ERP study

ObjectiveThis study examines the long-term impact of prenatal exposure to chemotherapy on executive functioning and the contribution of late-prematurity to this effect, using event-related potentials.MethodsMothers of the prenatal-exposed children (n = 20) were diagnosed with cancer and received chemotherapeutic treatment during pregnancy. We recruited healthy controls (n = 20) who were matched on a 1:1 ratio regarding prematurity, age and sex.We assessed executive functioning at the age of nine, using two event-related potential paradigms: a Go/Nogo paradigm to investigate processes of response inhibition and conflict monitoring, as well as a Posner paradigm to investigate spatial attention.ResultsLower potentials were found in prenatal-exposed children compared to controls in the Go/Nogo P3 and Posner positive slow wave. Moreover, prenatal-exposed children responded slower on the Posner paradigm compared to controls (p < .033), with more incorrect responses (p = .023). In the control group, the N2 Go/Nogo wave was more pronounced in children born after a longer gestation.ConclusionsThis is the first study that demonstrates an effect of prenatal exposure to chemotherapy on the development of executive functioning, not limited to the effect of late-prematurity.SignificanceThis study emphasizes the necessity of a long-term follow-up of prenatal-exposed children to re-inform clinical practice on the costs and benefits of late-premature induction over treatment during pregnancy.     

Bariatric surgery related proximal myopathy: A partially reversible complication

Deficiency neuropathies and rhabdomyolysis have previously been reported after bariatric surgery (BS) but never myopathies. We report cases of five patients with morbid obesity who developed within 2 to 4 months of a BS, proximal myopathy following significant and rapid weight loss worsened by postoperative gastrointestinal complications. Muscle weakness concerned lower limbs in particular in quadriceps and less frequently in upper limbs and diaphragm, sometimes mimicked a Guillain–Barré syndrome. Muscle biopsy performed in 1 patient, revealed selective atrophy of type 2 fibers. Weakness slowly decreased with refeeding with vitamins supplementation. We enlarge here the clinical pattern of post-BS complications.     

Mechanism of action of s1p receptor modulators in multiple sclerosis: The double requirement

The ideal treatment for multiple sclerosis (MS) would target both the neuroinflammatory component of the disease (peripheral and central) and its neurodegenerative component, via modulation of a ubiquitous and pleiotropic common target. Sphingosine-1-phosphate (S1P), a product of sphingosine metabolism, regulates many biological functions (including cell proliferation and survival, cell migration, the immune response and cardiovascular function) via five subtypes of receptor. These receptors are expressed in all types of brain cells where they modulate a number of processes involved in neuronal plasticity, including myelination, neurogenesis and neuroprotection. This profile has aroused interest in modulation of S1P function as a therapeutic target in many brain diseases, particularly those in which the immune system plays a role in the development of brain lesions. Fingolimod, a S1P receptor modulator, exerts its beneficial effects in MS through its anti-inflammatory and anti-neurodegenerative effects. This review discusses recent evidence indicating that fingolimod may target both the inflammatory and neurodegenerative components of the disease process in MS.     

Serial MRI alterations of pediatric patients with beta-propeller protein associated neurodegeneration (BPAN)

Background and PurposeBeta-propeller protein-associated neurodegeneration (BPAN) is one subtype of neurodegeneration with brain iron accumulation. It is difficult to diagnose BPAN due to the non-specificity of their clinical findings and neuroimaging in early childhood. We experienced four pediatric patients with serial brain MRI and evaluated the alteration of the findings through their course.MethodsWe retrospectively reviewed the clinical findings and 21 MRI findings of the four patients with genetically confirmed pediatric BPAN. We also performed a quantitative MR assessment using the quantitative susceptibility mapping (QSM) values of the globus pallidus (GP), substantia nigra (SN), and deep cerebellar nuclei (DCN) compared to 10 age-matched disease controls.ResultsOnly one patient was suspected of BPAN based on imaging findings before the genetic diagnosis was made. The other three patients could not be suspected until their Whole-exome sequencings (WES) done. In all four cases, no abnormal signals were noted in the GP and SN at the initial brain MRI, but hypointensities were observed after the ages of 4–7 years on T2-weighted images and after the ages of 2–7 years on susceptibility-weighted images. In three patients, T2 hyperintensity in the bilateral DCN was persistently observed throughout the observational period. Three patients showed transient T2 hyperintensity and swelling in the GP, SN and/or DCN during the episodes of pyrexia and seizures. The other findings included cerebral and cerebellar atrophy, thinning of the corpus callosum, and delayed myelination. The QSM values of the GP and SN were significantly higher in the patients compared to the controls (P = 0.005, respectively), but that of the DCN did not differ significantly (P = 0.16).ConclusionBrain MRI is a useful method to establish the early diagnosis of BPAN.