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Generation and accumulation of amyloid-β (Aβ) protein in the brain are the primary causes of Alzheimer's disease (AD). Alcadeins (Alcs composed of Alcα, Alcβ and Alcγ family) are a neuronal membrane protein that is subject to proteolytic processing, as is Aβ protein precursor (APP), by APP secretases. Previous observations suggest that Alcs are involved in the pathophysiology of Alzheimer's disease (AD). Here, we generated new mouse App NL-F (APP-KI) lines with either Alcα- or Alcβ-deficient background and analyzed APP processing and Aβ accumulation through the aging process. The Alcα-deficient APP-KI (APP-KI/Alcα-KO) mice enhanced brain Aβ accumulation along with increased amyloidogenic β-site cleavage of APP through the aging process whereas Alcβ-deficient APP-KI (APP-KI/Alcβ-KO) mice neither affected APP metabolism nor Aβ accumulation at any age. More colocalization of APP and BACE1 was observed in the endolysosomal pathway in neurons of APP-KI/Alcα-KO mice compared to APP-KI and APP-KI/Alcβ-KO mice. These results indicate that Alcα plays an important role in the neuroprotective function by suppressing the amyloidogenic cleavage of APP by BACE1 in the brain, which is distinct from the neuroprotective function of Alcβ, in which p3-Alcβ peptides derived from Alcβ restores the viability in neurons impaired by toxic Aβ., (© 2024. The Author(s).)

Context: Obesity is accompanied by damages to several tissues, including the brain. Pathological data and animal models have demonstrated an increased inflammatory reaction in hypothalamus and hippocampus., Objective: We tested whether we could observe such pathological modifications in vivo through quantitative magnetic resonance imaging (MRI) metrics., Methods: This prospective study was conducted between May 2019 and November 2022. The study was conducted in the Specialized Center for the Care of Obesity in a French University Hospital. Twenty-seven patients with obesity and 23 age and gender-paired normal-weight controls were prospectively recruited. All participants were examined using brain MRI. Anthropometric and biological data, eating behavior, anxiety, depression, and memory performance were assessed in both groups. The main outcome measure was brain MRI with the following parametric maps: quantitative susceptibility mapping (QSM), mean diffusivity (MD), fractional anisotropy (FA), magnetization transfer ratio map, and T2 relaxivity map., Results: In the hypothalamus, patients with obesity had higher FA and lower QSM than normal-weight controls. In the hippocampus, patients with obesity had higher FA and lower MD. There was no correlation between imaging biomarkers and eating behavior or anxiety., Conclusion: Our findings are consistent with the presence of neuroinflammation in brain regions involved in food intake. In vivo brain biomarkers from quantitative MRI appear to provide an incremental information for the assessment of brain damages in patients with obesity., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Objectives: Insulo-opercular surgery can cause ischemic motor complications. A source of this is the arteries around the superior limiting sulcus (SLS), which reach the corona radiata, but the detailed anatomy remains unclear. To characterize arteries around the SLS including the long insular arteries (LIAs) and long medullary arteries, we classified them and examined their distribution in relation to the SLS, which helps reduce the risk of ischemia., Methods: Twenty adult cadaveric hemispheres were studied. Coronal brain slices were created perpendicular to the SLS representing insular gyri (anterior short, middle short, posterior short, anterior long, and posterior long). The arteries within 10-mm proximity of the SLS that reached the corona radiata were excavated and classified by the entry point., Results: A total of 122 arteries were identified. Sixty-three (52%), 20 (16%), and 39 (32%) arteries penetrated the insula (LIAs), peak of the SLS, and operculum (long medullary arteries), respectively. 100 and six (87%) arteries penetrated within 5 mm of the peak of the SLS. The arteries were distributed in the anterior short gyrus (19%), middle short gyrus (17%), posterior short gyrus (20%), anterior long gyrus (19%), and posterior long gyrus (25%). Seven arteries (5.7%) had anastomoses after they penetrated the parenchyma., Conclusion: Approximately 90% of the arteries that entered the parenchyma and reached the corona radiata were within a 5-mm radius of the SLS in both the insula and operculum side. This suggests that using the SLS as a landmark during insulo-opercular surgery can decrease the chance of ischemia., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Kinesin super family (KIF) genes encode motor kinesins, a family of evolutionary conserved proteins, involved in intracellular trafficking of various cargoes. These proteins are critical for various physiological processes including neuron function and survival, ciliary function and ciliogenesis, and cell-cycle progression. Recent evidence suggests that alterations in motor kinesin genes can lead to a variety of human diseases, including monogenic disorders. Neuropathies, impaired higher brain functions, structural brain abnormalities and multiple congenital anomalies (i.e., renal, urogenital, and limb anomalies) can result from pathogenic variants in many KIF genes. We expand the phenotype associated with KIF4A variants from developmental delay and intellectual disability with or without epilepsy to a congenital anomaly phenotype with hydrocephalus and various brain anomalies at the more severe end of phenotypic manifestations. Additional anomalies of the kidneys and urinary tract, congenital lymphedema, eye, and dental anomalies seem to be variably associated and overlap with clinical signs observed in other kinesinopathies. Caution still applies to missense variants, but hopefully, future work will further establish genotype-phenotype correlations in a larger number of patients and functional studies may give further insights into the complex function of KIF4A., (© 2021 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

Corpus callosum anomalies (CCA) is a common congenital brain anomaly with various etiologies. Although one of the most important etiologies is genetic factors, the genetic background of CCA is heterogenous and diverse types of variants are likely to be causative. In this study, we analyzed 16 Japanese patients with corpus callosum anomalies to delineate clinical features and the genetic background of CCAs. We observed the common phenotypes accompanied by CCAs: intellectual disability (100%), motor developmental delay (93.8%), seizures (60%), and facial dysmorphisms (50%). Brain magnetic resonance imaging showed colpocephaly (enlarged posterior horn of the lateral ventricles, 84.6%) and enlarged supracerebellar cistern (41.7%). Whole exome sequencing revealed genetic alterations in 9 of the 16 patients (56.3%), including 8 de novo alterations (2 copy number variants and variants in ARID1B, CDK8, HIVEP2, and TCF4) and a recessive variant of TBCK. De novo ARID1B variants were identified in three unrelated individuals, suggesting that ARID1B variants are major genetic causes of CCAs. A de novo TCF4 variant and somatic mosaic deletion at 18q21.31-qter encompassing TCF4 suggest an association of TCF4 abnormalities with CCAs. This study, which analyzes CCA patients usung whole exome sequencing, demonstrates that comprehensive genetic analysis would be useful for investigating various causal variants of CCAs., (© 2021. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)

Background: The occipital transtentorial approach (OTA) is a very useful but challenging approach to expose the pineal region because the deep-seated arachnoid membranes usually fold and extend over the great vein of Galen (GVG), leading to dense and poor visibility. In addition, the practical aspects of arachnoid anatomy are not well understood. We aimed to develop a safe surgical procedure for the OTA according to the practical aspects of arachnoid anatomy., Methods: The procedure is shown through an illustrative video of surgery and cadaver. Five cadavers were analyzed for their arachnoid structures and the surgical procedures via the OTA, in strict compliance with legal and ethical requirements., Results: All cadavers showed a 2-layered arachnoid structure-one belonging to the occipital lobe, and the other to the cerebellum. According to our cadaveric analysis, the arachnoid attachment of the tentorial apex can be peeled bluntly, with an average distance of 10.2 mm. For our clinical presentation, a pineal tumor with hydrocephalus was detected in a 14-year-old boy. While using the OTA and expanding the deep surgical field, we detached the membrane from the tentorial apex and bluntly peeled it to reveal the deep veins. Finally, gross total removal of the tumor was achieved., Conclusions: A 2-layered arachnoid structure interposes the GVG from above and below the tentorium. The arachnoid membrane below the tentorium can be peeled off bluntly from the GVG to the attachment bundle limited by the penetrating veins. This detachment technique is useful for safe enlargement of the surgical field for the OTA., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Face-to-face imitation is a unique social interaction wherein a shared action is executed based on the feedback of the partner. Imitation by the partner is the feedback to the imitatee's action, resulting in sharing actions. The neural mechanisms of the shared representation of action during face-to-face imitation, the core of inter-subjectivity, are not well-known. Here, based on the predictive coding account, we hypothesized that the pair-specific forward internal model is the shared representation of action which is represented by the inter-individual synchronization of some portion of the mirror neuron system. Hyperscanning functional magnetic resonance imaging was conducted during face-to-face interaction in 16 pairs of participants who completed an immediate imitation task of facial expressions. Paired participants were alternately assigned to either an imitator or an imitatee who was prompted to express a happy, sad, or non-emotional face. While neural activation elicited by imitating and being imitated were distinct with little overlap, on-line imitative interaction enhanced inter-brain synchronization in the right inferior parietal lobule that correlated with the similarity in facial movement kinematic profile. This finding indicates a critical role of the right inferior parietal lobule in sharing representation of action as a pair-specific forward internal model through imitative interaction., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

It is not fully understood how enzymes are regulated in the tiny reaction field of a cell. Several enzymatic proteins form cytoophidia, a cellular macrostructure to titrate enzymatic activities. Here, we show that the epileptic encephalopathy-associated protein Tbc1d24 forms cytoophidia in neuronal cells both in vitro and in vivo. The Tbc1d24 cytoophidia are distinct from previously reported cytoophidia consisting of inosine monophosphate dehydrogenase (Impdh) or cytidine-5'-triphosphate synthase (Ctps). Tbc1d24 cytoophidia is induced by loss of cellular juvenescence caused by depletion of Gm14230, a juvenility-associated lncRNA (JALNC) and zeocin treatment. Cytoophidia formation is associated with impaired enzymatic activity of Tbc1d24. Thus, our findings reveal the property of Tbc1d24 to form cytoophidia to maintain neuronal cellular juvenescence., Competing Interests: The authors have declared that no competing interests exist.

Background: Although 7T functional MRI (fMRI) provides better signal-to-noise ratio and higher spatial resolution than 3T fMRI, geometric distortions become more challenging because fMRI is more susceptible to distortions than structural MRI. Accurate alignment of 7T fMRI to structural MRI data is critical for precise cortical surface-based analysis., Purpose: To quantify the effectiveness of distortion corrections of 7T fMRI data., Study Type: Prospective., Subjects: Fifteen healthy individuals aged 19-26 years (mean: 21.9 years)., Field Strength/sequence: Multiband gradient-echo echo-planar imaging sequence at 7T; 3D T 1 /T 2 -weighted sequences (magnetization prepared rapid acquisition with gradient echo [MPRAGE] and sampling perfection with application optimized contrast using different flip angle evolution [SPACE]) at 3T., Assessment: fMRI data at 7T were registered to cortical surfaces reconstructed from 3T structural data acquired in the same subjects. Distortions induced by B 0 inhomogeneity and gradient nonlinearity (B 0 and gradient distortions) were evaluated as cortical fallout (misregistration of noncortical areas) and displacement (misregistration along gray matter)., Statistical Tests: Repeated measures analyses of variance with post-hoc t-tests with Bonferroni correction., Results: The accuracy of fully corrected fMRI images based on the intensity distribution was 89.2%. Without any corrections, 9.7% of vertices in the whole surfaces were fallout and the average displacement was 0.96 mm for the rest of the vertices. B 0 and gradient distortion corrections significantly reduced the fallout (to 2.1% and 8.7%) and displacement (to 0.29 mm and 0.86 mm). These corrections were effective even around regions with moderate distortions (the somatosensory and visual cortices for B 0 distortion, and the anterior frontal, inferior temporal, and posterior occipital cortices for gradient distortion)., Data Conclusion: B 0 distortion correction is crucial for surface-based analysis of fine-resolution fMRI at 7T. Gradient distortion correction should be considered when regions of interest include regions distant from the isocenter of scanners., Evidence Level: 1 TECHNICAL EFFICACY STAGE: 1., (© 2020 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC. on behalf of International Society for Magnetic Resonance in Medicine.)

Much attention has been given to effects of repeated exposure to a shock wave as a possible factor causing severe higher brain dysfunction and post-traumatic stress disorder (PTSD)-like symptoms in patients with mild to moderate blast-induced traumatic brain injury (bTBI). However, it is unclear how the repeated exposure and the inter-exposure time affect the brain. In this study, we topically applied low-impulse (∼54 Pa·s) laser-induced shock waves (LISWs; peak pressure, ∼75.7 MPa) to the rat brain once or twice with the different inter-exposure times (15 min, 1 h, 3 h, 24 h and 7 days) and examined anxiety-related behavior and motor dysfunction in the rats as well as expression of β-amyloid precursor protein (APP) as an axonal damage marker in the brains of the rats. The averaged APP expression scores for the rat brains doubly-exposed to LISWs with inter-exposure times from 15 min to 24 h were significantly higher than those for rats with a single exposure (P < 0.0001). The rats with double exposure to LISWs showed significantly more frequent anxiety-related behavior (P < 0.05) and poorer motor function (P < 0.01) than those of rats with a single exposure. When the inter-exposure time was extended to 7 days, however, the rats showed no significant differences either in axonal damage score or level of motor dysfunction. The results suggest that the cumulative effects of shock wave-related brain injury can be avoided with an appropriate inter-exposure time. However, clinical bTBI occurs in much more complex environments than those in our model. Further study considering other factors, such as the effects of acceleration, is needed to know the clinically-relevant, necessary inter-exposure time., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Cell competition is a cell-cell interaction mechanism which maintains tissue homeostasis through selective elimination of unfit cells. During early brain development, cells are eliminated through apoptosis. How cells are selected to undergo elimination remains unclear. Here we aimed to identify a role for cell competition in the elimination of suboptimal cells using an in vitro neuroepithelial model. Cell competition was observed when neural progenitor HypoE-N1 cells expressing RAS V12 were surrounded by normal cells in the co-culture. The elimination through apoptosis was observed by cellular changes of RAS V12 cells with rounding/fragmented morphology, by SYTOX blue-positivity, and by expression of apoptotic markers active caspase-3 and cleaved PARP. In this model, expression of juvenility-associated genes Srsf7 and Ezh2 were suppressed under cell-competitive conditions. Srsf7 depletion led to loss of cellular juvenescence characterized by suppression of Ezh2, cell growth impairment and enhancement of senescence-associated proteins. The cell bodies of eliminated cells were engulfed by the surrounding cells through phagocytosis. Our data indicates that neuroepithelial cell competition may have an important role for maintaining homeostasis in the neuroepithelium by eliminating suboptimal cells through loss of cellular juvenescence.

Thiel's embalming method provides natural coloration, flexibility, and tissue plasticity, and is used widely to prepare specimens for cadaver surgical training. However, this method causes brain softening, thereby restricting the cadaver surgical training of intra-cranial procedures. In this study, three cadavers were embalmed using formalin fixation, Thiel's embalming method, and Thiel's embalming method with additional intra-cerebral ventricular formalin injection, respectively. We also established rat models of the three embalming methods to develop and determine the best method for retaining adequate brain elasticity. The intra-ventricular formalin injection in the cadaver was performed through the Kocher's point, as in the classical external ventricular drain procedure. Both, the cadaver brains and rat models yielded consistent shear wave measurements and brain surface stiffness data. Notably, the Thiel's embalming method with additional intra-cerebral ventricular formalin injection yielded suitable elasticity for brain cadaver surgical training in terms of brain mobilization and surgical field deployment, and also discharged formaldehyde in undetectable quantities. To our knowledge, this is the first report in which a fixed quality, namely, brain elasticity for the performance of head and brain cadaver surgical training, has been evaluated in a cadaver subjected to the Thiel's embalming method with immersion fixation in the cerebrospinal fluid space. We conclude that the Thiel's embalming method with additional intra-cerebral ventricular formalin injection can maintain the brain elasticity, and may therefore improve the quality of head and brain cadaver surgical training safely and easily.

Alzheimer's disease (AD) is a very common neurodegenerative disorder, chiefly caused by increased production of neurotoxic β-amyloid (Aβ) peptide generated from proteolytic cleavage of β-amyloid protein precursor (APP). Except for familial AD arising from mutations in the APP and presenilin ( PSEN ) genes, the molecular mechanisms regulating the amyloidogenic processing of APP are largely unclear. Alcadein α/calsyntenin1 (ALCα/CLSTN1) is a neuronal type I transmembrane protein that forms a complex with APP, mediated by the neuronal adaptor protein X11-like (X11L or MINT2). Formation of the ALCα-X11L-APP tripartite complex suppresses Aβ generation in vitro , and X11L-deficient mice exhibit enhanced amyloidogenic processing of endogenous APP. However, the role of ALCα in APP metabolism in vivo remains unclear. Here, by generating ALCα-deficient mice and using immunohistochemistry, immunoblotting, and co-immunoprecipitation analyses, we verified the role of ALCα in the suppression of amyloidogenic processing of endogenous APP in vivo We observed that ALCα deficiency attenuates the association of X11L with APP, significantly enhances amyloidogenic β-site cleavage of APP, especially in endosomes, and increases the generation of endogenous Aβ in the brain. Furthermore, we noted amyloid plaque formation in the brains of human APP-transgenic mice in an ALCα-deficient background. These results unveil a potential role of ALCα in protecting cerebral neurons from Aβ-dependent pathogenicity in AD., Competing Interests: Conflict of interest—The authors declare that they have no conflicts of interest with the contents of this article., (© 2020 Gotoh et al.)

Background: Recent studies have examined hypertrophic pachymeningitis as an IgG4-RD. However, there are no reports of immunoglobulin G4 (IgG4)-related hypertrophic pachymeningitis with polycystic subdural hygroma., Case Presentation: A 56-year-old man presented to the hospital with complaints of a persistent, pulsatile, occipital headache and general malaise. Magnetic resonance imaging of the brain revealed hypertrophic pachymeningitis with polycystic subdural hygroma and hematoma. Based on the dural biopsy findings and exclusion of other diseases, the patient was diagnosed with immunoglobulin G4 (IgG4)-related hypertrophic pachymeningitis. IgG4-related diseases may cause subdural hygroma more commonly than other diseases that cause hypertrophic pachymeningitis., Conclusions: This is the first case report discussing polycystic subdural hygroma and hematoma with IgG4-related hypertrophic pachymeningitis.

Imaging mass spectrometry (IMS) has been rarely used to examine specimens of human brain tumours. In the current study, high quality brain tumour samples were selected by tissue observation. Further, IMS analysis was combined with a new hierarchical cluster analysis (IMS-HCA) and region of interest analysis (IMS-ROI). IMS-HCA was successful in creating groups consisting of similar signal distribution images of glial fibrillary acidic protein (GFAP) and related multiple proteins in primary brain tumours. This clustering data suggested the relation of GFAP and these identified proteins in the brain tumorigenesis. Also, high levels of histone proteins, haemoglobin subunit α, tubulins, and GFAP were identified in a metastatic brain tumour using IMS-ROI. Our results show that IMS-HCA and IMS-ROI are promising techniques for identifying biomarkers using brain tumour samples.

Background: The purpose of this study was to investigate the effects of edaravone on nitric oxide (NO) production, hydroxyl radical (OH - ) metabolism, and neuronal nitric oxide synthase (nNOS) expression during cerebral ischemia and reperfusion., Methods: Edaravone (3 mg/kg) was administered intravenously to 14 C57BL/6 mice just before reperfusion. Eleven additional mice received saline (controls). NO production and OH - metabolism were continuously monitored using bilateral striatal in vivo microdialysis. OH - formation was monitored using the salicylate trapping method. Forebrain ischemia was produced in all mice by bilateral occlusion of the common carotid artery for 10 minutes. Levels of NO metabolites, nitrite (NO 2 - ), were determined using the Griess reaction. Brain sections were immunostained with an anti-nNOS antibody and the fractional area density of nNOS-immunoreactive pixels to total pixels determined.3 - ), were determined using the Griess reaction. Brain sections were immunostained with an anti-nNOS antibody and the fractional area density of nNOS-immunoreactive pixels to total pixels determined., Results: Blood pressure and regional cerebral blood flow were not significantly different between the edaravone and control groups. The levels of NO 2 - did not differ significantly between the 2 groups. The level of NO 3 - was significantly higher in the edaravone group compared with the control group after reperfusion. 2,3-dihydroxybenzoic acid levels were lower in the edaravone group compared with those in the control group after reperfusion. Immunohistochemistry showed nNOS expression in the edaravone group to be significantly lower than that in the control group 96 hours after reperfusion., Conclusions: These in vivo data indicate that edaravone may have a neuroprotective effect by reducing levels of OH - metabolites, increasing NO production and decreasing nNOS expression in brain cells., Competing Interests: Conflict of Interest The authors have no conflicts of interest to declare., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The aim of this study was to evaluate the effects of the carotid artery stenting (CAS) procedure on cerebral hemodynamics and cognitive performance in patients with internal carotid artery stenosis. In this prospective observational study, 16 consecutive patients in a single institute were treated with CAS from 2010 to 2011 (71.7 ± 7.3 years old, 12 males, and six left-sided procedures). Before and after the CAS procedure, all patients were evaluated with single photon emission computed tomography using 123 I-iodoamphetamine and acetazolamide as well as the Weschler Adult Intelligent Scale (WAIS) to assess three intelligent quotients and four indexes. Patients with decreased preprocedural cerebral blood flow (CBF) and cerebrovascular reserve (CVR) experienced significant increases in CBF and CVR (P = 0.01 and 0.03). Twelve (75%) patients experienced a significant increase in one or more WAIS scores, while two (13%) showed a significant decrease. The most frequently improved scores were the Working Memory Index and Processing Speed Index (seven patients/44%). Preprocedural CBF was significantly correlated with the Full-scale and Performance Intelligent Quotients (r = 0.51-0.56, P = 0.02-0.04), and patients who experienced a significant increase in these scores had larger increases in CVR than patients with unchanged scores (P = 0.0097-0.019). These results indicate that the CAS procedure improved impaired cerebral hemodynamics and might benefit the cognitive function of patients with internal carotid artery stenosis related to impaired cerebral hemodynamics.

MDGA1 (MAM domain-containing glycosylphosphatidylinositol anchor) has recently been linked to schizophrenia and bipolar disorder. Dysregulation of dopamine (DA) and serotonin (5-HT) systems has long been associated with schizophrenia and other neuropsychiatric disorders. Here, we measured prepulse inhibition (PPI) of the startle response and ex vivo tissue content of monoamines and their metabolites in the frontal cortex, striatum and hippocampus of Mdga1 homozygous (Mdga1-KO), Mdga1 heterozygous (Mdga1-HT) and wild-type (WT) male mice. We found that Mdga1-KO mice exhibited statistically significant impairment of PPI, and had higher levels of homovanillic acid in all three brain regions studied compared with Mdga1-HT and WT mice (P < 0.05), while levels of norepinephrine, DA and its metabolites 3,4-dihydroxyphenylacetic acid and 3-methoxytyramine remained unchanged. Mdga1-KO mice also had a lower 5-hydroxyindoleacetic acid level in the striatum (P < 0.05) compared with WT mice. 5-HT levels remained unchanged with the exception of a significant increase in the level in the cortex. These data are the first evidence suggesting that MDGA1 deficiency leads to a pronounced deficit in PPI and plays an important role in perturbation of DA and 5-HT metabolism in mouse brain; such changes may contribute to a range of neuropsychiatric disorders., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The impairment of learning and memory is a well-documented effect of both natural and synthetic cannabinoids. In the present study, we aimed to investigate the effect of acute administration of JWH-018, a synthetic cannabinoid, on the hippocampal metabolome to assess biochemical changes in vivo. JWH-018 elevated levels of the endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG). The increase of endocannabinoid levels in response to JWH-018 could be inhibited by co-administration of AM251, a CB1 receptor antagonist. Biochemical analyses revealed that this was the result of suppression of two hydrolases involved in endocannabinoid degradation (fatty acid amide hydrolase [FAAH] and monoacylglycerol lipase [MAGL]). Additionally, we showed that JWH-018 causes a reduction in the levels of brain-derived neurotrophic factor (BDNF), which is known to modulate synaptic plasticity and adaptive processes underlying learning and memory. The decrease of BDNF following JWH-018 treatment was also rescued by co-administration of AM251. As both endocannabinoids and BDNF have been shown to modulate learning and memory in the hippocampus, the alteration of their levels in response to JWH-018 may explain the contribution of synthetic cannabinoids to impairment of memory.

Introduction: Gerstmann-Sträussler-Scheinker disease P105L (GSS105) is a rare variant of GSS caused by a point mutation of the prion protein (PrP) gene at codon 105 (proline to leucine substitution). It is clinically characterized by spastic paraparesis and dementia and histopathologically defined by PrP-plaques in the brain. This report describes a clinicopathological analysis of three autopsied kindred from a Japanese GSS105 family, plus a topological analysis of PrP, hyperphosphorylated tau (p-tau), and beta-amyloid (Aβ)., Methods: Using paraffin-embedded sections, we applied histology and single- and multiple-labeling immunohistochemistry for PrP, p-tau, and Aβ to the three cases. Comparative semi-quantitative analyses of tissue injuries and PrP-plaques were also employed., Results: Case 1 (45 years old (yo)) and Case 2 (56 yo) are sisters, and Case 3 (49 yo) is the son of Case 2. Case 1 and Case 2 presented with spastic paraparesis followed by dementia, whereas Case 3 presented, not with spastic paraparesis, but with psychiatric symptoms. In Case 1 and Case 2, the brain showed tissue injuries with many PrP-plaques in the cerebral cortices, and the pyramidal tract showed myelin loss/pallor. In Case 3, the brain was least degenerated with a number of PrP-plaques; however, the pyramidal tract remained intact. In addition, p-tau was deposited in all cases, where p-tau was present in or around PrP-plaques. By double-labeling immunohistochemistry, the colocalization of p-tau with PrP-plaques was confirmed. Moreover in Case 2, Aβ was deposited in the cerebral cortices. Interestingly, not only p-tau but also Aβ was colocalized with PrP-plaques. In all cases, both three repeat tau and four repeat tau were associated with PrP-plaques., Conclusions: The clinicopathological diversity of GSS105, which is possible even in the same family, was ascertained. Not only p-tau but also Aβ could be induced by PrP ("secondary degeneration"), facilitating the kaleidoscopic symptoms of GSS., (© 2018 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.)

Objective: Individuals with autism spectrum disorder (ASD) often show characteristic differences in auditory processing. To clarify the mechanisms underlying communication impairment in ASD, we examined auditory language processing with both anatomical and functional methods., Methods: We assessed the language abilities of adolescents with ASD and typically developing (TD) adolescents, and analyzed the surface-based morphometric structure between the groups using magnetic resonance imaging. Furthermore, we measured cortical responses to an auditory word comprehension task with magnetoencephalography and performed network-based statistics using the phase locking values., Results: We observed no structural differences between the groups. However, the volume of the left ventral central sulcus (vCS) showed a significant correlation with linguistic scores in ASD. Moreover, adolescents with ASD showed weaker cortical activation in the left vCS and superior temporal sulcus. Furthermore, these regions showed differential correlations with linguistic scores between the groups. Moreover, the ASD group had an atypical gamma band (25-40 Hz) network centered on the left vCS., Conclusions: Adolescents with ASD showed atypical responses on the auditory word comprehension task and functional brain differences., Significance: Our results suggest that phonological processing and gamma band cortical activity play a critical role in auditory language processing-related pathophysiology in adolescents with ASD., (Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Tumor angiogenesis has attracted increasing attention because of its potential as a valuable marker in the differential diagnosis of brain tumors as well as a novel therapeutic target. Prostate-specific membrane antigen (PSMA) is expressed by the neovasculature endothelium of some tumors, with little to no expression by the tumor cells or normal vasculature endothelium. The aim of this study was to investigate the potential of PSMA for the evaluation of the tumor neovasculature of various brain tumors and the possibility of detecting PSMA expression in brain tumors using PET imaging with 89 Zr-Df-IAB2M (anti-PSMA minibody). Eighty-three tissue specimens including gliomas, metastatic brain tumors, primary central nervous system lymphomas (PCNSL), or radiation necroses were analyzed by immunohistochemical staining with PSMA antibody. 89 Zr-Df-IAB2M PET scans were performed in three patients with recurrent high-grade gliomas or metastatic brain tumor. PSMA was highly expressed in the vascular endothelium of high-grade glioma and metastatic brain tumor, whereas PSMA was poorly expressed in the vascular endothelium of PCNSL and radiation necrosis. PSMA expression in high-grade gliomas and a metastatic brain tumor was clearly visualized by PET imaging with 89 Zr-Df-IAB2M. Furthermore, a trend toward a positive correlation between the degree of 89 Zr-Df-IAB2M uptake and PSMA expression levels in tumor specimens was observed. PET imaging of PSMA using 89 Zr-Df-IAB2M may have potential value in the differential diagnosis of high-grade glioma from PCNSL or radiation necrosis as well as in the prediction of treatment efficacy and assessment of treatment response to bevacizumab therapy for high-grade glioma.

Objective: The objective of this study was to show the effect of the number of sampling points (NS) and the maximum b value (bmax) on fiber crossing detection in diffusion spectrum imaging (DSI) in clinical practice., Methods: We performed 3-Tesla DSI in which we changed the NS (62-258) while keeping bmax at 8000 s/mm and in which we changed the bmax (4000-8000 s/mm) while keeping the NS at 129. The superior longitudinal fasciculus volume and the proportion of nerve voxels in which at least 2 (Rcr2) or 3 (Rcr3) nerve fiber bundles crossed were calculated., Results: When bmax was set to 8000 s/mm, mean Rcr2 and Rcr3 values and superior longitudinal fasciculus volumes significantly increased with higher NSs, but they did not significantly change when we varied bmax with 129 NS., Conclusions: Depiction sensitivity of nerve fiber crossing in DSI improves at higher NS and bmax settings, but a bmax insensitivity appears at an intermediate NS such as 129.

An android, i.e., a realistic humanoid robot with human-like capabilities, may induce an uncanny feeling in human observers. The uncanny feeling about an android has two main causes: its appearance and movement. The uncanny feeling about an android increases when its appearance is almost human-like but its movement is not fully natural or comparable to human movement. Even if an android has human-like flexible joints, its slightly jerky movements cause a human observer to detect subtle unnaturalness in them. However, the neural mechanism underlying the detection of unnatural movements remains unclear. We conducted an fMRI experiment to compare the observation of an android and the observation of a human on which the android is modelled, and we found differences in the activation pattern of the brain regions that are responsible for the production of smooth and natural movement. More specifically, we found that the visual observation of the android, compared with that of the human model, caused greater activation in the subthalamic nucleus (STN). When the android's slightly jerky movements are visually observed, the STN detects their subtle unnaturalness. This finding suggests that the detection of unnatural movements is attributed to an error signal resulting from a mismatch between a visual input and an internal model for smooth movement.

Brain tryptophan and its neuroactive metabolites play key roles in central fatigue. However, previous brain function analysis targets may have included both glia and neurons together. Here, we clarified the fatigue-cognitive circuit of the central-peripheral linkage, including the role of glial-neuronal interaction in cognition. Using a rat model of central fatigue induced by chronic sleep disorder (CFSD), we isolated presynaptic terminals and oligodendrocytes. Results showed that compared to control group, presynaptic levels of tryptophan, kynurenine, and kynurenic acid, but not serotonin, in the CFSD group were higher in the hypothalamus and hippocampus. Moreover, CFSD group had higher oligodendrocytic levels of tryptophan, and impaired spatial cognitive memory accuracy and increased hyperactivity and impulsivity. These findings suggest that dynamic change in glial-neuronal interactions within the hypothalamus-hippocampal circuit causes central fatigue, and increased tryptophan-kynurenic acid pathway activity in this circuit causes reduced cognitive function. Additionally, CFSD group had 1.5 times higher plasma levels of tryptophan and kynurenine. Furthermore, in rats undergoing intraperitoneal administration of kynurenine (100mg/kg) versus vehicle, kynurenine-treated rats showed enhanced production of kynurenic acid in the hippocampus, with suppressed recall of retained spatial cognitive memory. The study revealed that uptake of periphery-derived kynurenine and tryptophan into the brain enhances kynurenic acid production in the brain, and the three factors produce amplification effect involved in the role of central-peripheral linkage in central fatigue, triggering cognitive dysfunction., (Copyright © 2017 Elsevier B.V. All rights reserved.)

This study aimed to determine whether a bismuth-coated latex shield (B-shield) could protect the eyes during brain SPECT/CT. Methods: A shield containing the heavy metal bismuth (equivalent to a 0.15-mm-thick lead shield) was placed over a cylindric phantom and the eyes of a 3-dimensional brain phantom filled with 99m Tc solution. Subsequently, phantoms with and without the B-shield were compared using SPECT/CT. The CT parameters were 30-200 mA and 130 kV. The dose reduction achieved by the B-shield was measured using a pencil-shaped ionization chamber. The protective effects of the B-shield were determined by evaluating relative radioactivity concentration as well as artifacts (changes in CT number), linear attenuation coefficients, and coefficients of variation on SPECT images. Results: The radiation doses with and without the B-shield were 0.14-0.77 and 0.36-1.93 mGy, respectively, and the B-shield decreased the average radiation dose by about 60%. The B-shield also increased the mean CT number, but only at locations just beneath the surface of the phantom. Streaks of higher density near the underside of the B-shield indicated beam hardening. Linear attenuation coefficients and the coefficients of variation did not significantly differ between phantoms with and without the B-shield, and the relative 99m Tc radioactivity concentrations were not affected. Conclusion: The B-shield decreased the radiation dose without affecting estimated attenuation correction or radioactivity concentrations. Although surface artifacts increased with the B-shield, the quality of the SPECT images was acceptable. B-shields can help protect pediatric patients and patients with eye diseases who undergo SPECT imaging., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose: A fast spin-echo sequence based on the Periodically Rotated Overlapping Parallel Lines with Enhanced Reconstruction (PROPELLER) technique is a magnetic resonance (MR) imaging data acquisition and reconstruction method for correcting motion during scans. Previous studies attempted to verify the in vivo capabilities of motion-corrected PROPELLER in real clinical situations. However, such experiments are limited by repeated, stray head motion by research participants during the prescribed and precise head motion protocol of a PROPELLER acquisition. Therefore, our purpose was to develop a brain phantom set for motion-corrected PROPELLER., Materials and Methods: The profile curves of the signal intensities on the in vivo T 2 -weighted image (T 2 WI) and 3-D rapid prototyping technology were used to produce the phantom. In addition, we used a homemade driver system to achieve in-plane motion at the intended timing. We calculated the Pearson's correlation coefficient (R 2 ) between the signal intensities of the in vivo T 2 WI and the phantom T 2 WI and clarified the rotation precision of the driver system. In addition, we used the phantom set to perform initial experiments to show the rotational angle and frequency dependences of PROPELLER., Results: The in vivo and phantom T 2 WIs were visually congruent, with a significant correlation (R 2 ) of 0.955 (p<.001). The rotational precision of the driver system was within 1 degree of tolerance. The experiment on the rotational angle dependency showed image discrepancies between the rotational angles. The experiment on the rotational frequency dependency showed that the reconstructed images became increasingly blurred by the corruption of the blades as the number of motions increased., Conclusions: In this study, we developed a phantom that showed image contrasts and construction similar to the in vivo T 2 WI. In addition, our homemade driver system achieved precise in-plane motion at the intended timing. Our proposed phantom set could perform systematic experiments with a real clinical MR image, which to date has not been possible in in vivo studies. Further investigation should focus on the improvement of the motion-correction algorithm in PROPELLER using our phantom set for what would traditionally be considered problematic patients (children, emergency patients, elderly, those with dementia, and so on)., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: Cerebral arteriolar vasomotor function plays an important role in brain health. Since respiratory changes in the partial arterial pressure of CO 2 (PaCO 2 ) cause arterioles to vasodilate or vasoconstrict, resting-state arteriolar vasomotion results in the fluctuation of venous blood oxygenation, which can be monitored by observing magnetic resonance (MR) signals. Focusing on the superior sagittal sinus as the largest cerebral vein, we developed a method to elucidate the respiratory fluctuation of cerebral venous oxygenation that may reflect the vasomotor function., Methods: Single slices of varying thickness (7-15 mm) taken perpendicular to the superior sagittal sinus of five volunteers were imaged by spin-echo echo-planar imaging using a 1.5-T MR system. The time series of the signal intensity at the superior sagittal sinus was Fourier-transformed, and the spectral fluctuation intensity (SFI) at respiratory frequency was obtained. The amplitude of the respiratory fluctuation in the cerebral venous oxygenation was calculated from the gradient of the relation between the SFI and the average signal intensity, which increased proportionally with an increase in slice thickness. The amplitude of the fluctuation in cerebral venous oxygenation at low (<0.1 Hz) and cardiac pulsation frequencies was also calculated for comparison with the respiratory fluctuation., Results: The amplitude of respiratory fluctuation in the cerebral venous oxygenation was quantified as 1.2%, demonstrating the validity of our method via the highest significant correlation (r = 0.82) in the plot of SFI and average signal intensities; the correlations at low and cardiac pulsation frequencies were 0.60 and 0.63, respectively., Conclusion: We have successfully demonstrated cerebral venous oxygenation fluctuation at respiratory frequencies in the resting state. This fluctuation was non-invasively evaluated as 1.2%, representing the control value for the arteriolar vasomotor function of a healthy human.

Twenty-one vegetative state (VS) patients and 10 minimally conscious state (MCS) patients were treated by spinal cord stimulation (SCS) following an electrophysiological evaluation 3 months or more after the onset of brain injury.A flexible four-contact cylindrical electrode was inserted into the epidural space of the cervical vertebrae, and placed at cervical levels C2-C4. Five-hertz stimulation was applied for 5 min every 30 min during the daytime at an intensity that produced muscle twitches of the upper extremities.Both the fifth wave in the auditory brainstem response (ABR) and N20 in the somatosensory evoked potential (SEP) were detected in 8 of the 21 VS patients and 9 of the 10 MCS patients. Of the 3 VS patients and 7 MCS patients who recovered following SCS therapy, all showed a preserved fifth wave in the ABR and N20 in the SEP, and all had received SCS therapy within 9 months after the onset of brain injury. Although the 3 patients who recovered from VS remained in a bedridden state, all 7 patients who recovered from MCS were able to emerge from the bedridden state within 12 months after the start of SCS.Five-hertz cervical SCS caused increased cerebral blood flow (CBF) and induced muscle twitches of the upper extremities, and MCS patients showed a remarkable recovery of consciousness and motor function in the upper extremities compared with the lower extremities. This SCS method could be a new neuromodulation and neurorehabilitation technique, and MCS patients may be good candidates for SCS therapy.

Their aim was to examine whether microvascular leakage of endogenous albumin, a representative marker for blood-brain barrier (BBB) damage, was induced in the periventricular area of diabetic db/db mice because periventricular white matter hyperintensity formation in magnetic resonance images was accelerating in elderly patients with diabetes mellitus. Using light and electron microscopes, and semi-quantitative analysis techniques, immunoreactivity of endogenous albumin, indicating vascular permeability, was examined in the periventricular area and spinal cord of db/db mice and db/+m control mice. Greater immunoreactivity of albumin was observed in the vessel wall of the periventricular area of db/db mice than in controls. Additionally, weak immunoreactivity was observed in the spinal cord of both db/db mice and controls. The number of gold particles, indicating immunoreactivity of albumin, in the perivascular area of db/db mice was significantly higher than that of control mice, but there was no significant difference in the number of particles in the spinal cord between db/db mice and controls. These findings suggest that albumin microvascular leakage, or BBB breakdown, is induced in the periventricular area of diabetic mice. Microsc. Res. Tech. 79:833-837, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Purpose: We retrospectively evaluated the imaging spectrum of Pelizaeus-Merzbacher disease (PMD) in correlation with the clinical course and genetic abnormality., Methods: We collected the magnetic resonance imaging (MRI) findings of 19 genetically proven PMD patients (all males, aged 0-29years old) using our integrated web-based MRI data collection system from 14 hospitals. The patterns of hypomyelination were determined mainly by the signals of the cerebrum, corticospinal tract, and brainstem on T2-weighted images (T2WI). We assessed the degree of myelination age on T1-weighted images (T1WI) and T2WI independently, and we evaluated cerebellar and callosal atrophy. The clinical severity and genetic abnormalities (causal mutations of the proteolipid protein gene PLP1) were analyzed together with the imaging findings., Results: The clinical stage tended to be more severe when the whole brainstem, or corticospinal tract in the internal capsule showed abnormally high intensity on T2WI. Diffuse T2-high signal of brainstem was observed only in the patients with PLP1 point mutation. Myelination age "before birth" on T1WI is a second manifestation correlated with the clinically severe phenotypes. On the other hand, eight patients whose myelination ages were > 4months on T1WI were associated with mild clinical phenotypes. Four of them showed almost complete myelination on T1WI with a discrepancy in myelination age between T1WI and T2WI. A random and patchy pattern of myelination on T2WI was noted in one patient with PLP1 point mutation. Advanced myelination was observed in three of the seven followed-up patients. Four patients had atrophy of the cerebellum, and 17 patients had atrophy of the corpus callosum., Conclusion: Our multicenter study has demonstrated a wide variety of imaging findings of PMD. Signal intensity of brainstem and corticospinal tract of internal capsule would be the points to presume clinical severity in PMD patients. The spectrum of MRI findings should be kept in mind to diagnose PMD and to differentiate from other demyelinating leukodystrophies., (Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Aims of Study: It is reported that severe bladder disorder in idiopathic normal-pressure hydrocephalus (iNPH) is predicted by right frontal hypoperfusion. However, it is not known whether bladder recovery is predicted by brain perfusion change after shunt surgery. To address this issue, we compared bladder and brain function before and after shunt surgery in iNPH., Methods: We enrolled 75 patients in the study. Before and 12 months after shunt surgery, we analyzed brain perfusion by SPECT and bladder disorder by a specialized grading scale. The scale consisted of grade 0, none; grade 1, urinary urgency and frequency; grade 2, urinary incontinence 1-3 times a week; grade 3, urinary incontinence >daily; and grade 4, loss of bladder control. More than one grade improvement is defined as improvement, and more than one grade decrement as worsening; otherwise no changes., Results: Comparing before and after surgery, in the bladder-no-change group (32 cases) there was an increase in blood flow which is regarded as reversal of enlargement in the Sylvian fissure and lateral ventricles (served as control). In contrast, in the bladder-improved group (32 cases) there was an increase in bilateral mid-cingulate, parietal, and left frontal blood flow (p < 0.05). In the bladder-worsened group (11 cases) no significant blood flow change was observed., Conclusion: The present study showed that after shunt surgery, bladder recovery is related with mid-cingulate perfusion increase in patients with iNPH. The underlying mechanism might be functional restoration of the mid-cingulate that normally inhibits the micturition reflex.

l-2-Hydroxyglutaric aciduria (l-2-HGA) is a rare inborn error of metabolism. Mainly, patients with this disorder exhibit neurological symptoms and characteristic neuroradiological findings, such as subcortical white matter abnormalities, which are believed to be caused by the toxicity of the accumulation of l-2-hydroxyglutaric acid. A genotype-first approach of the whole exome sequence was used to identify compound heterozygous mutations, c.584A>G (p.Y195C) and c.772T>C (p.C258R), in L2HGDH, the gene responsible for this disorder, in an adult patient with intellectual disability and intractable epilepsy. A retrospective assay confirmed the increased concentrations of 2-hydroxyglutaric acid in the urine. These results suggested that neuroradiological findings of subcortical white matter abnormalities are characteristic of l-2-HGA and that clinical exome sequencing has sufficient power to compensate for insufficient clinical evaluations., (Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Background: Patients with major depressive disorder (MDD) exhibit cognitive impairment, and evidence suggests that the semantic version of the verbal fluency task is a reliable cognitive marker of the disorder. Here, using functional magnetic resonance imaging (fMRI), we investigated the dysfunction of neural processing in acute depression and examined the effects of a 6-week pharmacological intervention., Methods: Sixteen patients with MDD participated in 2 fMRI sessions, and 16 healthy control (HC) subjects participated in 1 fMRI session. During each fMRI session, the participants performed a semantic verbal fluency task. Brain activity during the task was compared between groups (MDD 1st fMRI vs. HC) and times (MDD 1st fMRI vs. 2nd fMRI)., Results: Significant brain hypoactivation was observed in MDD patients at the prefrontal, lateral parietal, and limbic regions compared to HC, and MDD patients exhibited hyperactivation at the left precuneus compared to HC. Hypoactivity of the left dorsolateral prefrontal cortex (DLPFC) and hyperactivity of the precuneus were normalized with treatment., Conclusions: Hypoactivation of the left DLPFC and hyperactivation of the precuneus should be considered as dysregulation of anticorrelated brain networks during a cognitive demanding task. This failure of network regulation may be an important factor in the pathophysiology of MDD., (© 2017 S. Karger AG, Basel.)

1 H-MRS (proton magnetic resonance spectroscopy) is a method for analyzing material components using the difference of the frequency (chemical shift) in magnetic resonance. 1 H-MRS for human body is able to diagnose the clinical conditions by non-invasive analysis of materials in organs. However, the mechanical limitations and complexity in analyses prevented it from becoming popular as MRI (magnetic resonance imaging). Recently, an ideal environment for 1 H-MRS is commonly available such as stronger magnetic field and improved software, yet we still lack common knowledges about 1 H-MRS which makes whom plans to start it difficult. In this article, the principle, tips, clinical applications and spectrum evaluations were explained focusing on novice users.

Many new microdeletion syndromes have been characterized in the past decade, including 2p15-p16.1 microdeletion syndrome. More than 10 patients with this syndrome have been described. Recently, we encountered two additional patients with 2p15-p16.1 microdeletion syndrome. All patients showed variable degrees of intellectual disability, with the autistic features characteristic of this syndrome. Seven out of 16 patients (44%) showed structural abnormalities in the brain, which is also an important feature of this syndrome. The shortest region of microdeletion overlap among the patients includes two genes, USP34 and XPO1. Although these genes have some functional relevance to cancer, they have not been associated with neurological functions. Diagnosis of additional patients with 2p15-p16.1 microdeletion syndrome and identification of pathogenic mutations in this region will help identify the genes responsible for the neurological features of the syndrome., (© 2015 Japanese Teratology Society.)

Objective: Criteria for motor evoked potential (MEP) monitoring include the amplitude criterion and threshold criterion. The aim of our study for the amplitude criterion during removal of brain lesions was to determine a suitable stimulus intensity that can reduce the variability in amplitudes. We also assessed the usefulness of the threshold criterion and amplitude criterion by comparing the variability between the two methods as a preliminary study., Methods: Seventeen patients including 12 cases with no neurological deterioration after surgery were enrolled in this study. The amplitudes in various stimulus intensities and the stimulation threshold (ST) were repeatedly measured during surgery. The stimulus intensities used in the amplitude criterion are described as 'the ST just after dura opening (ST(0))+additional intensity'. The variability was assessed with the coefficient of variation (CV)., Results: With direct cortical stimulation (DCS), the CVs of amplitudes were significantly lower at stimulus intensities of more than ST(0)+4 mA, with the smallest at ST(0)+10 mA. The CV of STs was significantly smaller than that of amplitudes., Conclusions: The variability in the amplitude criterion was significantly reduced using stimulus intensities of more than ST(0)+4 mA. The variability in the threshold criterion was significantly smaller than that of the amplitude criterion, even when using a strong stimulus intensity., Significance: The maximal stimulus intensity with no body motion should be used in the amplitude criterion for intraoperative MEP elicited by DCS., (Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Objective: To determine the prognostic factors for encephalopathy with bright tree appearance (BTA) in the acute phase through retrospective case evaluation., Methods: We recruited 10 children with encephalopathy who presented with BTA and classified them into 2 groups. Six patients with evident regression and severe psychomotor developmental delay after encephalopathy were included in the severe group, while the remaining 4 patients with mild mental retardation were included in the mild group. We retrospectively analyzed their clinical symptoms, laboratory data, and magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) findings., Results: Patients in the severe group developed subsequent complications such as epilepsy and severe motor impairment. Univariate analysis revealed that higher maximum lactate dehydrogenase (LDH) levels (p=0.055) were a weak predictor of poor outcome. Maximum creatinine levels were significantly higher (p<0.05) and minimal platelet counts were significantly lower (p<0.05) in the severe group than in the mild group. Acute renal failure was not observed in any patient throughout the study. MRS of the BTA lesion during the BTA period showed elevated lactate levels in 5 children in the severe group and 1 child in the mild group. MRI performed during the chronic phase revealed severe brain atrophy in all patients in the severe group., Conclusions: Higher creatinine and LDH levels and lower platelet counts in the acute phase correlated with poor prognosis. Increased lactate levels in the BTA lesion during the BTA period on MRS may predict severe physical and mental disability., (Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

We reported a 64-year-old autopsy case, showing a unique combination of disorders in visceral organs and brain. She had developmental delay, microencephaly, and facial dysmorphism. She developed sick sinus syndrome and liver cirrhosis. There were no abnormalities in laboratory tests for congenital metabolic errors or anomaly syndromes, including activities of lysosomal enzymes, isoelectric focusing of serum transferrin or array comparative genomic hybridization. She died of cardiorespiratory failure. At autopsy she showed liver cirrhosis and mesangial proliferation. The brain weighed 710 g. Bizarre putaminal changes were found, in which the size of area of putamen in coronal sections was small, aberrant fiber running was increased, and immunoreactivity for tyrosine hydroxylase was reduced. Loss of Purkinje cells was found throughout the cerebellar cortex. She had unreported combination of developmental delay, facial dysmorphism, small brain, bizarre putaminal lesion, cerebellar atrophy, cardiac disease, liver cirrhosis and renal disease. Although the exact cause of disease still remains to be investigated, it will be a clue for the establishment of new disease entity to accumulate subjects having the similar phenotype., (Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

A 77-year-old man scheduled for coronary artery bypass grafting underwent left superficial temporal artery-middle cerebral artery anastomosis (STA MCA). Before anesthesia, we planned to insert an intraaortic balloon pump as a perioperative circulatory assist. In addition, a fiberoptic catheter was inserted in the proximity of the right jugular bulb to monitor jugular venous oxygen saturation (Sjv(O2)) as an index of the balance between cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2). Continuous infusion of nicorandil was started prior to induction of anesthesia. General anesthesia was induced with remifentanil, propofol and rocuronium, and was maintained with oxygen, air, remifentanil and propofol. After induction of anesthesia, blood pressure decreased from 160/70 mmHg to 100/50 mmHg. There was no abnormality of electrocardiogram. However, Sjv(O2) decreased from 58% to 40%. Ephedrine was immediately injected and continuous infusion of dopamine was started. Blood pressure increased and Sjv(O2) was improved to > 55%. Thereafter, his operative course was uneventful. Sjv(O2) is normally approximately 55-75%. If Sjv(O2) is < 50%, therapy (s) directed at increasing CBF and/or decreasing CMRO2 should be initiated. Sjv(O2) monitoring can be used to determine the minimal blood pressure that should be maintained to avoid cerebral ischemia in the case of STA-MCA.

This paper documents the case of a female Japanese patient with infantile focal epilepsy, which was different from benign infantile seizures, and a family history of infantile convulsion and paroxysmal choreoathetosis. The patient developed partial seizures (e.g., psychomotor arrest) at age 14 months. At the time of onset, interictal electroencephalography (EEG) showed bilateral parietotemporal spikes, but the results of neurologic examination and brain magnetic resonance imaging were normal. Her seizures were well controlled with carbamazepine, and she had a normal developmental outcome. EEG abnormalities, however, persisted for more than 6 years, and the spikes moved transiently to the occipital area and began to resemble the rolandic spikes recognized in benign childhood epilepsy. Her father had paroxysmal kinesigenic dyskinesia, with an onset age of 6 years, and her youngest sister had typical benign infantile seizures. Genetic analysis demonstrated that all affected members had a heterozygous mutation of c.649&#95;650insC in the proline-rich transmembrane protein-2 (PRRT2) gene. This case indicates that the phenotypic spectrum of infantile seizures or epilepsy with PRRT2-related pathology may be larger than previously expected, and that genetic investigation of the effect of PRRT2 mutations on idiopathic seizures or epilepsy in childhood may help elucidate the pathological backgrounds of benign childhood epilepsy., (Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Typical markers of protein aging are spontaneous post-translational modifications such as amino acid racemization (AAR) and amino acid isomerization (AAI) during the degradation of peptides. The post-translational AAR and AAI could significantly induce the density and localization of plaque deposition in brain tissues. Alzheimer's disease (AD) is reliably related to the formation and aggregation of amyloid-β peptide (Aβ) plaques in the human brain. No current analytical methods can simultaneously determine AAR and AAI during the degradation of Aβ from AD patients. We now report a covalent chiral derivatized ultraperformance liquid chromatography tandem mass spectrometry (CCD-UPLC-MS/MS) method for the determination of post-translational AAR and AAI of N-terminal Aβ (N-Aβ1-5) in human brain tissues. When subjected to tryptic N-Aβ1-5 from post-translationally modified natural Aβ in focal brain tissues by the CCD procedure, it was monitored at m/z 989.6→637.0/678.9 during electrospray collision-induced dissociation. These N-Aβ1-5 fragments with l-aspartic acid (l-Asp), d-Asp, l-isoAsp, and d-isoAsp could be separated using the UPLC system with a conventional reversed-phase column and mobile phase. The quantification of these peptides was determined using a stable isotope [(15)N]-labeled Aβ1-40 internal standard. The CCD-UPLC-MS/MS assay of potential N-Aβ1-5 allowed for the discovery of the present and ratio levels of these N-Aβ1-5 sequences with l-Asp, d-Asp, l-isoAsp, and d-isoAsp.

Pyrethroids are one of the most widely used classes of insecticides and show neurotoxic effects that induce oxidative stress in the neonatal rat brain. However, little is still known about effects of prenatal exposure to permethrin on vascular development in fetal brain, central nervous system development, and adult offspring behaviors. In this study, the effects of prenatal exposure to permethrin on the development of cerebral arteries in fetal brains, neurotransmitter in neonatal brains, and locomotor activities in offspring mice were investigated. Permethrin (0, 2, 10, 50, and 75 mg/kg) was orally administered to pregnant females once on gestation day 10.5. The brains of permethrin-treated fetuses showed altered vascular formation involving shortened lengths of vessels, an increased number of small branches, and, in some cases, insufficient fusion of the anterior communicating arteries in the area of circle of Willis. The prenatal exposure to permethrin altered neocortical and hippocampus thickness in the mid brain and significantly increased norepinephrine and dopamine levels at postnatal day 7 mice. For spontaneous behavior, the standing ability test using a viewing jar and open-field tests showed significant decrease of the standing ability and locomotor activity in male mice at 8 or 12 weeks of age, respectively. The results suggest that prenatal exposure to permethrin may affect insufficient development of the brain through alterations of vascular development., (Copyright © 2011 Wiley Periodicals, Inc., A Wiley Company.)