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Objective Methods Results Interpretation This study aimed to investigate the clinical characteristics and predictors of relapse in double negative atypical inflammatory demyelinating disease (IDD) and to explore potential antigenic targets by tissue‐based assays (TBA) using rat brain indirect immunofluorescence.We compared the clinical, laboratory, and MRI data of double negative atypical IDD with other IDD patients. Serum samples were collected for TBA. The predictors of relapse were examined over a minimum of 24 months follow‐up.In our cohort of 98 patients with double negative atypical IDD, there was no significant female predominance (58.2%, 57/98). The lesions primarily affected the spinal cord and brain stem, with fewer cases of involvement in the area postrema (5.1%, 5/98) and longitudinally extensive transverse myelitis (43.9%, 43/98). A total of 62.5% (50/80) patients tested positive for anti‐astrocyte antibodies based on rat brain TBA. Over a median duration of 39.5 months, 80 patients completed the entire follow‐up, and 47.5% (38/80) patients exhibited monophasic course. A total of 36% (18/50) patients positively for anti‐astrocyte antibodies had a monophasic course, which is significantly lower than patients negatively for anti‐astrocyte antibodies (66.7%, 20/30) (p = 0.008). The presence of anti‐astrocyte antibodies (hazard ratio (HR), 2.243; 95% CI, 1.087–4.627; p = 0.029) and ≥4 cerebrum lesions at first attack (HR, 2.494; 95% CI, 1.224–5.078; p = 0.012) were risk factors for disease relapse, while maintenance immunotherapy during remission (HR, 0.361; 95% CI, 0.150–0.869; p = 0.023) was protective factor.Double negative atypical IDD are unique demyelinating diseases with a high relapse rate. Maintenance immunotherapy is helpful to the prevention of relapse, particularly in patients with anti‐astrocyte antibodies or ≥4 cerebrum lesions at first attack. [ABSTRACT FROM AUTHOR]

Background Purpose Methods Results Conclusion Patients may undergo anatomical changes during radiotherapy, leading to an underdosing of the target or overdosing of the organs at risk (OARs).This study developed a deep‐learning method to predict the tumor response of patients with nasopharyngeal carcinoma (NPC) during treatment. This method can predict the anatomical changes of a patient.The participants included 230 patients with NPC. The data included planning computed tomography (pCT) and routine cone‐beam CT (CBCT) images. The CBCT image quality was improved to the CT level using an advanced method. A long short‐term memory network‐generative adversarial network (LSTM‐GAN) is proposed, which can harness the forecasting ability of LSTM and the generation ability of GAN. Four models were trained to predict the anatomical changes that occurred in weeks 3–6 and named LSTM‐GAN‐week 3 to LSTM‐GAN‐week 6. The pCT and CBCT were used as input, and the tumor target volumes (TVs) and OARs were delineated on the predicted and real images (ground truth). Finally, the models were evaluated using contours and dosimetry parameters.The proposed method predicted the anatomical changes, with a dice similarity coefficient above 0.94 and 0.90 for the TVs and surrounding OARs, respectively. The dosimetry parameters were close between the prediction and ground truth. The deviations in the prescription, minimum, and maximum doses of the tumor targets were below 0.5 Gy. For serial organs (brain stem and spinal cord), the deviations in the maximum dose were below 0.6 Gy. For parallel organs (bilateral parotid glands), the deviations in the mean dose were below 0.8 Gy.The proposed method can predict the tumor response to radiotherapy in the future such that adaptation can be scheduled on time. This study provides a proactive mechanism for planning adaptation, which can enable personalized treatment and save clinical time by anticipating and preparing for treatment strategy adjustments. [ABSTRACT FROM AUTHOR]

Objective: Our aim was to survey astrocyte and microglial activation across four brain regions in a mouse model of chronic migraine. Background: Chronic migraine is a leading cause of disability, with higher rates in females. The role of central nervous system neurons and glia in migraine pathophysiology is not fully elucidated. Preclinical studies have shown abnormal glial activation in the trigeminal nucleus caudalis of male rodents. No current reports have investigated glial activation in both sexes in other important brain regions involved with the nociceptive and emotional processing of pain. Methods: The mouse nitroglycerin model of migraine was used, and nitroglycerin (10 mg/kg) or vehicle was administered every other day for 9 days. Prior to injections on days 1, 5, and 9, cephalic allodynia was determined by periorbital von Frey hair testing. Immunofluorescent staining of astrocyte marker, glial fibrillary protein (GFAP), and microglial marker, ionized calcium binding adaptor molecule 1 (Iba1), in male and female trigeminal nucleus caudalis, periaqueductal gray, somatosensory cortex, and nucleus accumbens was completed. Results: Behavioral testing demonstrated increased cephalic allodynia in nitroglycerin‐ versus vehicle‐treated mice. An increase in the percent area covered by GFAP+ cells in the trigeminal nucleus caudalis and nucleus accumbens, but not the periaqueductal gray or somatosensory cortex, was observed in response to nitroglycerin. No significant differences were observed for Iba1 staining across brain regions. We did not detect significant sex differences in GFAP or Iba1 quantification. Conclusions: Immunohistochemical analysis suggests that, at the time point tested, immunoreactivity of GFAP+ astrocytes, but not Iba1+ microglia, changes in response to chronic migraine‐associated pain. Additionally, there do not appear to be significant differences between males and females in GFAP+ or Iba1+ cells across the four brain regions analyzed. Plain Language Summary: The aim of this study was to determine if supportive immune cells in the brains of males and females are altered in an animal model of chronic migraine. Mice in the chronic migraine group showed significant activation of astrocytes, but not microglia, in male and female mice in pain and emotion‐processing brain regions. These results suggest that some supportive cells in the brain may play a role in regulating chronic migraine. [ABSTRACT FROM AUTHOR]

Brainstem metastases (BSM) present a significant neuro‐oncological challenge, resulting in profound neurological deficits and poor survival outcomes. Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) offer promising therapeutic avenues for BSM despite their precarious location. This international multicenter study investigates the efficacy and safety of SRS and FSRT in 136 patients with 144 BSM treated at nine institutions from 2005 to 2022. The median radiographic and clinical follow‐up periods were 6.8 and 9.4 months, respectively. Predominantly, patients with BSM were managed with SRS (69.4%). The median prescription dose and isodose line for SRS were 18 Gy and 65%, respectively, while for FSRT, the median prescription dose was 21 Gy with a median isodose line of 70%. The 12‐, 24‐, and 36‐month local control (LC) rates were 82.9%, 71.4%, and 61.2%, respectively. Corresponding overall survival rates at these time points were 61.1%, 34.7%, and 19.3%. In the multivariable Cox regression analysis for LC, only the minimum biologically effective dose was significantly associated with LC, favoring higher doses for improved control (in Gy, hazard ratio [HR]: 0.86, p <.01). Regarding overall survival, good performance status (Karnofsky performance status, ≥90%; HR: 0.43, p <.01) and prior whole brain radiotherapy (HR: 2.52, p <.01) emerged as associated factors. In 14 BSM (9.7%), treatment‐related adverse events were noted, with a total of five (3.4%) radiation necrosis. SRS and FSRT for BSM exhibit efficacy and safety, making them suitable treatment options for affected patients. [ABSTRACT FROM AUTHOR]

Transcutaneous auricular vagus nerve stimulation (taVNS) targets subcutaneous axons in the auricular branch of the vagus nerve at the outer ear. Its non‐invasive nature makes it a potential treatment for various disorders. taVNS induces neuromodulatory effects within the nucleus of the solitary tract (NTS), and due to its widespread connectivity, the NTS acts as a gateway to elicit neuromodulation in both higher‐order brain regions and other brainstem nuclei (e.g. spinal trigeminal nucleus; Sp5). Our objective was to examine stimulation parameters on single‐neuron electrophysiological responses in α‐chloralose‐anaesthetized Sprague–Dawley rats within NTS and Sp5. taVNS was also compared to traditional cervical VNS (cVNS) on single neuronal activation. Specifically, electrophysiological extracellular recordings were evaluated for a range of frequency and intensity parameters (20–250 Hz, 0.5–1.0 mA). Neurons were classified as positive, negative or non‐responders based on increased activity, decreased activity or no response during stimulation, respectively. Frequency‐dependent analysis showed that 20 and 100 Hz generated the highest proportion of positive responders in NTS and Sp5 with 1.0 mA intensities eliciting the greatest magnitude of response. Comparisons between taVNS and cVNS revealed similar parameter‐specific activation for caudal NTS neuronal populations; however, individual neurons showed different activation profiles. The latter suggests that cVNS and taVNS send afferent input to NTS via different neuronal pathways. This study demonstrates differential parameter‐specific taVNS responses and begins an investigation of the mechanisms responsible for taVNS modulation. Understanding the neuronal pathways responsible for eliciting neuromodulatory effects will enable more tailored taVNS treatments in various clinical disorders. Key points: Transcutaneous auricular vagus nerve stimulation (taVNS) offers a non‐invasive alternative to invasive cervical vagus nerve stimulation (cVNS) by activating vagal afferents in the ear to induce neuromodulation.Our study evaluated taVNS effects on neuronal firing patterns in the nucleus of the solitary tract (NTS) and spinal trigeminal nucleus (Sp5) and found that 20 and 100 Hz notably increased neuronal activity during stimulation in both nuclei.Increasing taVNS intensity not only increased the number of neurons responding in Sp5 but also increased the magnitude of response, suggesting a heightened sensitivity to taVNS compared to NTS.Comparisons between cVNS and taVNS revealed similar overall activation but different responses on individual neurons, indicating distinct neural pathways.These results show parameter‐specific and nuclei‐specific responses to taVNS and confirm that taVNS can elicit responses comparable to cVNS at the neuronal level, but it does so through different neuronal pathways. [ABSTRACT FROM AUTHOR]

Summary: Light has many non‐image‐forming functions including modulation of pupil size and stimulation of alertness and cognition. Part of these non‐image‐forming effects may be mediated by the brainstem locus coeruleus. The processing of sensory inputs can be associated with a transient pupil dilation that is likely driven in part by the phasic activity of the locus coeruleus. In the present study, we aimed to characterise the task‐evoked pupil response associated with auditory inputs under different light levels and across two cognitive tasks. We continuously monitored the pupil of 20 young healthy participants (mean [SD] 24.05 [4.0] years; 14 women) whilst they completed an attentional and an emotional auditory task whilst exposed to repeated 30–40‐s blocks of light interleaved with darkness periods. Blocks could either consist of monochromatic orange light (0.16 melanopic equivalent daylight illuminance (EDI) lux) or blue‐enriched white light of three different levels [37, 92, 190 melanopic EDI lux; 6500 K]. For the analysis, 15 and then 14 participants were included in the attentional and emotional tasks, respectively. Generalised linear mixed models showed a significant main effect of light level on the task‐evoked pupil responses triggered by the attentional and emotional tasks (p ≤ 0.0001). The impact of light was different for the target versus non‐target stimulus of the attentional task but was not different for the emotional and neutral stimulus of the emotional task. There is a smaller sustained pupil size during brighter light blocks but, a higher light level triggers a stronger task‐evoked pupil response to auditory stimulation, presumably through the recruitment of the locus coeruleus. [ABSTRACT FROM AUTHOR]

Background: Multi‐shell diffusion characteristics may help characterize brainstem gliomas (BSGs) and predict H3K27M status. Purpose: To identify the diffusion characteristics of BSG patients and investigate the predictive values of various diffusion metrics for H3K27M status in BSG. Study Type: Prospective. Population: Eighty‐four BSG patients (median age 10.5 years [IQR 6.8–30.0 years]) were included, of whom 56 were pediatric and 28 were adult patients. Field Strength/Sequence: 3 T, multi‐shell diffusion imaging. Assessment: Diffusion kurtosis imaging and neurite orientation dispersion and density imaging analyses were performed. Age, gender, and diffusion metrics, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity, radial diffusivity (RD), mean kurtosis (MK), axial kurtosis (AK), radial kurtosis, intracellular volume fraction (ICVF), orientation dispersion index, and isotropic volume fraction (ISOVF), were compared between H3K27M‐altered and wildtype BSG patients. Statistical Tests: Chi‐square test, Mann–Whitney U test, multivariate analysis of variance (MANOVA), step‐wise multivariable logistic regression. P‐values <0.05 were considered significant. Results: 82.4% pediatric and 57.1% adult patients carried H3K27M alteration. In the whole group, the H3K27M‐altered BSGs demonstrated higher FA, AK and lower RD, ISOVF. The combination of age and median ISOVF showed fair performance for H3K27M prediction (AUC = 0.78). In the pediatric group, H3K27M‐altered BSGs showed higher FA, AK, MK, ICVF and lower RD, MD, ISOVF. The combinations of median ISOVF, 5th percentile of FA, median MK and median MD showed excellent predictive power (AUC = 0.91). In the adult group, H3K27M‐altered BSGs showed higher ICVF and lower RD, MD. The 75th percentile of RD demonstrated fair performance for H3K27M status prediction (AUC = 0.75). Data Conclusion: Different alteration patterns of diffusion measures were identified between H3K27M‐altered and wildtype BSGs, which collectively had fair to excellent predictive value for H3K27M alteration status, especially in pediatric patients. Evidence Level: 2 Technical Efficacy: Stage 3 [ABSTRACT FROM AUTHOR]

Objectives: Neuroimaging studies have advanced our understanding of the intricate central nervous system control network governing lower urinary tract (LUT) function, shedding light on mechanisms for urine storage and voiding. However, a lack of consensus in methodological approaches hinders the comparability of results among research groups and limits the translation of this knowledge to clinical applications, emphasizing the need for standardized methodologies and clinical utilization guidelines. Methods: This paper reports the discussions of a workshop at the 2023 meeting of the International Consultation on Incontinence Research Society, which reviewed uncertainties and research priorities to progress the field of neuroimaging in LUT control and dysfunction. Results: Neuroimaging holds great potential for improving our understanding of LUT control and pathophysiological conditions. To date, functional neuroimaging techniques have not yet achieved sufficient strength to make a direct clinical impact. Potential approaches that can improve the clinical utilization of neuroimaging were discussed and research questions proposed. Conclusions: Neuroimaging offers a valuable tool for investigating LUT control, but it's essential to acknowledge the potential for oversimplification when interpreting brain activity due to the complex neural processing and filtering of sensory information. Moreover, technical limitations pose challenges in assessing key brain stem and spinal cord centers, particularly in cases of neurological dysfunction, highlighting the need for more reliable imaging of these centers to advance our understanding of LUT function and dysfunction. [ABSTRACT FROM AUTHOR]

The 2021 World Health Organization (WHO) classification of the central nervous system (CNS) tumors has classified diffuse leptomeningeal glioneuronal tumor (DLGNT) as a mixed neuronal and glial tumor. Here, we report a DLGNT with two distinct morphological tumor components but identical molecular features. A four‐year‐old female child presented with progressive right upper extremity weakness. Magnetic resonance imaging (MRI) revealed the leptomeningeal enhancement over the brain stem and cervicothoracic spine. The histological examination of surgical specimens revealed two distinct tumor components: approximately half of the tumor is composed of oligodendroglioma‐like tumor intermingled with nodules of ganglioglioma‐like tumor. Immunohistochemistry confirmed the oligodendroglioma and ganglioglioma features. The molecular genetic studies demonstrated the features of DLGNT, including fusion of KIAA1549::BRAF, deletion of chromosome 1p, and absence of isocitrate dehydrogenase 1/2 (IDH1/2) mutation in both tumor components. Interestingly, the genetic studies also revealed the distinct chromosomal abnormalities of the loss of chromosome 4 only in oligodendroglioma‐like tumor and copy neutral loss of heterozygosity of 7Q34Q36.3 in the ganglioglioma‐like tumor component. This case highlights the critical role of molecular testing in the diagnosis of rare cases of DLGNT with diverse morphological components as well as in the identification of unique molecular alternations responsible for morphological phenotypes of the distinct tumors in DLGNT. [ABSTRACT FROM AUTHOR]

This document discusses the challenges and considerations involved in administering anesthesia to a child with Michel's aplasia undergoing auditory brainstem implantation (ABI). Michel's aplasia is a condition where the inner ear structures are absent, rendering cochlear implants ineffective and necessitating the use of an ABI. The surgery requires a multidisciplinary team and careful monitoring. The document provides a case report of a successful surgery and emphasizes the importance of proper patient selection and anesthetic management. It also addresses various aspects of the procedure, including monitoring techniques, premedication, intraoperative concerns, extubation assessment, postoperative care, and rehabilitation. The document concludes by stating that ABIs offer a safe and effective option for auditory rehabilitation in patients who are not suitable candidates for cochlear implants, but further research is needed to determine the long-term benefits of the device. [Extracted from the article]

Background: X‐linked adrenoleukodystrophy (X‐ALD) is the most common peroxisomal disorder attributed to ABCD1 mutations. Case reports with predominant brainstem involvement are rare. Case Presentation: In this study, we reported a plateau male worker of X‐ALD characterized by progressive weakness accompanied by gait instability, mild nystagmus, and constipation. After 2 years of onset, a brain Magnetic Resonance Image (MRI) scan showed no abnormality but genetic analysis revealed a heterozygous mutation (c.1534G>A) in the ABCD1 gene. After 7 years of onset, although the patient was given aggressive dietary and symptomatic treatment in the course of the disease, a brain MRI scan showed predominantly brainstem damage, but serum concentrations of very long‐chain fatty acids were normal, and he had been bedridden for almost 2 years with severe bladder dysfunction, forcing him to undergo cystostomy. The patient was discharged with improved urinary retention and renal function. Conclusions: We reported an X‐ALD patient with a novel ABCD1 variation characterized by brainstem damage and retrospectively summarized the clinical manifestation, MRI features, and genetic features of X‐ALD patients with brainstem damage. [ABSTRACT FROM AUTHOR]

Objective: To identify the most common locations of cluster headache pain from an international, non–clinic‐based survey of participants with cluster headache, and to compare these locations to other cluster headache features as well as to somatotopic maps of peripheral, brainstem, thalamic, and cortical areas. Background: Official criteria for cluster headache state pain in the orbital, supraorbital, and/or temporal areas, yet studies have noted pain extending beyond these locations, and the occipital nerve appears relevant, given the effectiveness of suboccipital corticosteroid injections and occipital nerve stimulation. Furthermore, cranial autonomic features vary between patients, and it is not clear if the trigeminovascular reflex is dermatome specific (e.g., do patients with maxillary or V2 division pain have more rhinorrhea?). Finally, functional imaging studies show early activation of the posterior hypothalamus in a cluster headache attack. However, the first somatosensory area to be sensitized is unclear; the first area can be hypothesized based on the complete map of pain locations. Methods: The International Cluster Headache Questionnaire was an internet‐based cross‐sectional survey that included a clickable pain map of the face. These data were compared to several other datasets: (1) a meta‐analysis of 22 previous publications of pain location in cluster headache (consisting of 6074 patients); (2) four cephalic dermatome maps; (3) participants' survey responses for demographics, autonomic features, and effective medications; and (4) previously published somatotopic maps of the brainstem, thalamus, primary somatosensory cortex, and higher order somatosensory cortex. Results: One thousand five hundred eighty‐nine participants completed the pain map portion of the survey, and the primary locations of pain across all respondents was the orbital, periorbital, and temporal areas with a secondary location in the lower occiput; these primary and secondary locations were consistent with our meta‐analysis of 22 previous publications. Of the four cephalic dermatomes (V1, V2, V3, and a combination of C2‐3), our study found that most respondents had pain in two or more dermatomes (range 85.7% to 88.7%, or 1361–1410 of 1589 respondents, across the four dermatome maps). Dermatomes did not correlate with their respective autonomic features or with medication effectiveness. The first area to be sensitized in the canonical somatosensory pathway is either a subcortical (brainstem or thalamus) or higher order somatosensory area (parietal ventral or secondary somatosensory cortices) because the primary somatosensory cortex (area 3b) and somatosensory area 1 have discontinuous face and occipital regions. Conclusions: The primary pain locations in cluster headache are the orbital, supraorbital, and temporal areas, consistent with the official International Classification of Headache Disorders criteria. However, activation of the occiput in many participants suggests a role for the occipital nerve, and the pain locations suggest that somatosensory sensitization does not start in the primary somatosensory cortex. Plain Language Summary: Cluster headache (CH) pain is often thought to be located in or around the eye; however, multiple studies have documented pain elsewhere, and procedures that target nerves in the back of the head can help CH. In this large survey (1604 respondents) with a clickable pain map of the face, we found that (1) most respondents had pain extending beyond the area of the eye, and (2) the pain location did not correlate with autonomic symptoms, medication effectiveness, or other CH features. Cluster headache pain beyond the eye is common, and based on the pattern of areas activated, we hypothesized which parts of the brain's somatosensory system may be activated first in cluster attacks. [ABSTRACT FROM AUTHOR]

Background: Pain thresholds and primary headaches, including cluster headache attacks, have circadian rhythmicity. Thus, they might share a common neuronal mechanism. Objective: This study aimed to elucidate how the modulation of nociceptive input in the brainstem changes from noon to midnight. Insights into the mechanism of these fluctuations could allow for new hypotheses about the pathophysiology of cluster headache. Methods: This repeated measure observational study was conducted at the University Hospital Zurich from December 2019 to November 2022. Healthy adults between 18 and 85 years of age were eligible. All participants were examined at noon and midnight. We tested the pain threshold on both sides of the foreheads with quantitative sensory testing, assessed tiredness levels, and obtained high‐field (7 Tesla) and high‐resolution functional magnetic resonance imaging (MRI) at each visit. Functional connectivity was assessed at the two visits by performing a region‐of‐interest analysis. We defined nuclei in the brainstem implicated in processing nociceptive input as well as the thalamus and suprachiasmatic nucleus as the region‐of‐interest. Results: Ten people were enrolled, and seven participants were included. First, we did not find statistically significant differences between noon and midnight of A‐delta‐mediated pain thresholds (median mechanical pain threshold at noon: left 9.2, right 9.2; at night: left 6.5, right 6.1). Second, after correction for a false discovery rate, we found changes in the mechanical pain sensitivity to have a statistically significant effect on changes in the functional connectivity between the left parabrachial nucleus and the suprachiasmatic nucleus (T = −40.79). Conclusion: The MRI data analysis suggested that brain stem nuclei and the hypothalamus modulate A‐delta‐mediated pain perception; however, these changes in pain perception did not lead to statistically significantly differing pain thresholds between noon and midnight. Hence, our findings shed doubt on our hypothesis that the physiologic circadian rhythmicity of pain thresholds could drive the circadian rhythmicity of cluster headache attacks. Plain Language Summary: We wanted to find out if cluster headache attacks occur primarily at night because even healthy persons are more likely to feel pain at that time. Our sample of healthy participants did not have lower pain thresholds in the evening than at noon, and brain imaging suggested that the measurements were accurate. Thus, we could not prove our idea. [ABSTRACT FROM AUTHOR]

Food deprivation drives eating through multiple signals and circuits. Decreased glucose availability (i.e., cytoglucopenia) drives eating and also increases the value of sucrose. Ventral tegmental area (VTA) dopamine neurons (DANs) contribute to the evaluation of taste stimuli, but their role in integrating glucoprivic signals remains unknown. We monitored VTA DAN activity via Cre‐dependent expression of a calcium indicator with in vivo fibre photometry. In ad libitum fed rats, intraoral sucrose evoked a phasic increase in DAN activity. To manipulate glucose availability, we administered (intraperitoneal, lateral or fourth ventricular) the antiglycolytic agent 5‐thio‐D‐glucose (5TG), which significantly augmented the phasic DAN activity to sucrose. 5TG failed to alter DAN activity to water or saccharin, suggesting the response was selective for caloric stimuli. 5TG enhancement of sucrose‐evoked DAN activity was stronger after fourth ventricular administration, suggesting a critical node of action within the hindbrain. As 5TG also increases blood glucose, in a separate study, we used peripheral insulin, which stimulates eating, to decrease blood glucose—which was associated with increased DAN activity to intraoral sucrose. DAN activity developed to a cue predictive of intraoral sucrose. While 5TG augmented cue‐evoked DAN activity, its action was most potent when delivered to the lateral ventricle. Together, the studies point to central glucose availability as a key modulator of phasic DAN activity to food and food‐cues. As glucose sensing neurons are known to populate the hypothalamus and brainstem, results suggest differential modulation of cue‐evoked and sucrose‐evoked DAN activity. [ABSTRACT FROM AUTHOR]

Neurons exhibit a high energetic need, and the question arises as how they metabolically adapt to changing activity states. This is relevant for interpreting functional neuroimaging in different brain areas. Particularly, neurons with a broad firing range might exhibit metabolic adaptations. Therefore, we studied MNTB (medial nucleus of the trapezoid body) principal neurons, which generate action potentials (APs) at frequencies up to several hundred hertz. We performed the experiments in acute brainstem slices of the Mongolian gerbil (Meriones unguiculatus) at 22.5–24.5°C. Upon electrical stimulation of afferent MNTB fibres with 400 stimuli at varying frequencies, we monitored autofluorescence levels of NAD(P)H and FAD and determined the extremum amplitudes of their biphasic response. Additionally, we compared these data with alterations in O2 concentrations measured with an electrochemical sensor. These O2 changes are prominent since MNTB neurons rely on oxidative phosphorylation as shown by our pharmacological experiments. We calculated the O2 consumption rate as change in O2 concentration divided by stimulus durations, because these periods varied inversely with stimulus frequency as a result of the constant number of 400 stimuli applied. The O2 consumption rate increased with stimulation frequency up to a constant value at 600 Hz; that is, energy demand depends on temporal characteristics of activity despite the same number of stimuli. The rates showed no correlation with peak amplitudes of NAD(P)H or FAD, whilst the values of the two molecules were linearly correlated. This points at the complexity of analysing autofluorescence imaging for quantitative metabolic studies, because these values report only relative net changes of many superimposed oxidative and reductive processes. Monitoring O2 concentration rates is, thus, an important tool to improve the interpretation of NAD(P)H/FAD autofluorescence data, as they do not under all conditions and in all systems appropriately reflect the metabolic activity or energy demand. [ABSTRACT FROM AUTHOR]

Roving eye movement (RoEM), commonly seen in unconscious patients with significant cortical dysfunction but without apparent brainstem damage, has unclear prognostic significance. We describe a case of presumed hypoglycemic encephalopathy with RoEM, where the patient emerged from a 4‐day coma. While previous reports often associate RoEM cases with poor prognosis, cases with favorable outcomes exist, particularly among young patients or those with reversible conditions. Our findings highlight the variable neurological prognosis of RoEM, suggesting the possibility of improved consciousness and neurological recovery in certain pathologies, thus enhancing our understanding of RoEM's implications. [ABSTRACT FROM AUTHOR]

Key Clinical Message: In patients with lung adenocarcinoma, angiogenesis‐altering drugs can alter the appearance of leptomeningeal metastasis on magnetic resonance imaging (MRI) scans. In the ventral brainstem, this can manifest as a unique, linear, non‐enhancing T2‐hyperintense signal. [ABSTRACT FROM AUTHOR]

Parkinsonism‐dystonia‐2 PKDYS2 is an autosomal‐recessive disorder, caused by pathogenic biallelic variants in SLC18A2 which encodes the vesicular monoamine transporter (VMAT2) protein. PKDYS2 is a treatable neurotransmitter disease, and the rate of diagnosis of this disorder has increased significantly with the advance of genomic technologies. Our report highlights a novel pathologic variant in one case and a novel finding on MRI Brain, consisting of a normal symmetrical signal intensity in the dorsal brainstem and pons, and it substantiates the significance of genetic testing in the evaluation of children with developmental delays, which influences clinical decisions to enhance patient outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Sodium MRI is challenging because of the low tissue concentration of the 23Na nucleus and its extremely fast biexponential transverse relaxation rate. In this article, we present an iterative reconstruction framework using dual‐echo 23Na data and exploiting anatomical prior information (AGR) from high‐resolution, low‐noise, 1H MR images. This framework enables the estimation and modeling of the spatially varying signal decay due to transverse relaxation during readout (AGRdm), which leads to images of better resolution and reduced noise resulting in improved quantification of the reconstructed 23Na images. Methods: The proposed framework was evaluated using reconstructions of 30 noise realizations of realistic simulations of dual echo twisted projection imaging (TPI) 23Na data. Moreover, three dual echo 23Na TPI brain datasets of healthy controls acquired on a 3T Siemens Prisma system were reconstructed using conventional reconstruction, AGR and AGRdm. Results: Our simulations show that compared to conventional reconstructions, AGR and AGRdm show improved bias‐noise characteristics in several regions of the brain. Moreover, AGR and AGRdm images show more anatomical detail and less noise in the reconstructions of the experimental data sets. Compared to AGR and the conventional reconstruction, AGRdm shows higher contrast in the sodium concentration ratio between gray and white matter and between gray matter and the brain stem. Conclusion: AGR and AGRdm generate 23Na images with high resolution, high levels of anatomical detail, and low levels of noise, potentially enabling high‐quality 23Na MR imaging at 3T. [ABSTRACT FROM AUTHOR]

Purpose: Trigeminal neuralgia (TN) can be treated on the CyberKnife system using two different treatment delivery paths: the general‐purpose full path corrects small rotations, while the dedicated trigeminal path improves dose fall‐off but does not allow rotational corrections. The study evaluates the impact of uncorrected rotations on brainstem dose and the length of CN5 (denoted as Leff) covered by the prescription dose. Methods and materials: A proposed model estimates the delivered dose considering translational and rotational delivery errors for TN treatments on the CyberKnife system. The model is validated using radiochromic film measurements with and without rotational setup error for both paths. Leff and the brainstem dose is retrospectively assessed for 24 cases planned using the trigeminal path. For 15 cases, plans generated using both paths are compared for the target coverage and toxicity to the brainstem. Results: In experimental validations, measured and estimated doses agree at 1%/1 mm level. For 24 cases, the treated Leff is 5.3 ± 1.7 mm, reduced from 5.9 ± 1.8 mm in the planned dose. Constraints for the brainstem are met in 23 cases for the treated dose but require frequent treatment interruption to maintain rotational corrections <0.5° using the trigeminal path. The treated length of CN5, and plan quality metrics are similar for the two paths, favoring the full path where rotations are corrected. Conclusions: We validated an analytical model that can provide patient‐specific tolerances on rotations to meet plan objectives. Treatment using the full path can reduce treatment time and allow for rotational corrections. [ABSTRACT FROM AUTHOR]

An editorial focuses on challenging the conventional understanding of migraine pathophysiology, particularly the role of aura in initiating migraine attacks. It emphasizes that aura may not be the cause but rather an epiphenomenon of migraine, with the decision to initiate an attack occurring days before aura onset, likely in the limbic system.

The dorsal nucleus of the lateral lemniscus (DNLL) is a GABAergic, reciprocally connected auditory brainstem structure that continues to develop postnatally in rodents. One key feature of the DNLL is the generation of a strong, prolonged, ionotropic, GABAA receptor‐mediated inhibition. Possible GABAB receptor‐mediated signalling is unexplored in the DNLL. Here, we used Mongolian gerbils of either sex to describe GABAB receptor‐mediated modulation of postsynaptic potassium currents and synaptic inputs in postnatal (P) animals of days 10/11 and 23–28. Throughout development, we observed the presence of a Baclofen‐activated GABAB receptor‐enhanced potassium outward conductance that is capable of suppressing action potential generation. In P10/11, old gerbils GABAB receptor activation enhances glutamatergic and suppresses ionotropic GABAergic synaptic transmission. During development, this differential modulation becomes less distinct, because in P22–28, old animals Baclofen‐activated GABAB receptors rather enhance ionotropic GABAergic synaptic transmission, whereas glutamatergic transmission is both enhanced and suppressed. Blocking GABAB receptors causes an increase in ionotropic GABAergic transmission in P10/11 old gerbils that was independent on stimulation frequency but depended on the type of short‐term plasticity. Together with the lack of Baclofen‐induced changes in the synaptic paired‐pulse ratio of either input type, we suggest that GABAB receptor‐mediated modulation is predominantly postsynaptic and activates different signalling cascades. Thus, we argue that in DNLL neurons, the GABAB receptor is a post‐synaptically located signalling hub that alters signalling cascades during development for distinct targets. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the safety and efficacy of chloral hydrate in auditory brainstem response (ABR) tests. Setting and Design: In this study, the authors systematically searched both English (Embase, PubMed, and Web of Science) and Chinese (Chinese National Knowledge Infrastructure, Wanfang Data, and VIP Chinese Science) databases. Two authors independently performed data extraction and quality assessment. The pooled sedation failure rate and the pooled incidence of adverse events were calculated via a random‐effects model. Sensitivity and subgroup analyses were performed to explore the sources of heterogeneity, and the PRISMA guideline was followed. Participants: Patients with ABR tests receiving chloral hydrate sedation. Main outcome measures: The pooled sedation failure rate and the pooled incidence of adverse events. Results: A total of 23 clinical studies were included in the final analysis. The pooled sedation failure rate of patients who received chloral hydrate sedation before ABR examination was 10.0% [95% confidence interval (CI) (6.7%, 15.0%), I2 = 95%, p <.01]. There were significant differences in the prevalence of sedation failure between sample sizes greater than 200 and those less than or equal to 200 (5.6% vs. 19.6%, p <.01) and between the studies that reported sleep deprivation and those that did not report sleep deprivation (7.1% vs. 18.9%, p <.01). The pooled incidence of adverse events was 10.32% [95% CI (5.83%, 14.82%), I2 = 98.1%, p <.01]. Conclusions: Chloral hydrate has a high rate of sedation failure, adverse events, and potential carcinogenicity. Therefore, replacing its use in ABR tests with safer and more effective sedatives is warranted. [ABSTRACT FROM AUTHOR]

Epileptic seizures are seen as a result of changing excitability balance depending on the deterioration in synaptic plasticity in the brain. Neuroplastin, and its related molecules which are known to play a role in synaptic plasticity, neurotransmitter activities that provide balance of excitability and, different neurological diseases, have not been studied before in epilepsy. In this study, a total of 34 Sprague–Dawley male and female rats, 2 months old, weighing 250–300 g were used. The epilepsy model in rats was made via pentylenetetrazole (PTZ). After the completion of the experimental procedure, the brain tissue of the rats were taken and the histopathological changes in the hippocampus and cortex parts and the brain stem were investigated, as well as the immunoreactivity of the proteins related to the immunohistochemical methods. As a result of the histopathological evaluation, it was determined that neuron degeneration and the number of dilated blood vessels in the hippocampus, frontal cortex, and brain stem were higher in the PTZ status epilepticus (SE) groups than in the control groups. It was observed that neuroplastin and related proteins TNF receptor‐associated factor 6 (TRAF6), Gamma amino butyric acid type A receptors [(GABA(A)], and plasma membrane Ca2+ ATPase (PMCA) protein immunoreactivity levels increased especially in the male hippocampus, and only AMPA receptor subunit type 1 (GluA1) immunoreactivity decreased, unlike other proteins. We believe this may be caused by a problem in the mechanisms regulating the interaction of neuroplastin and GluA1 and may cause problems in synaptic plasticity in the experimental epilepsy model. It may be useful to elucidate this mechanism and target GluA1 when determining treatment strategies. [ABSTRACT FROM AUTHOR]

Objectives: The new daily persistent headache (NDPH) is a rare primary headache disorder. However, the underlying mechanisms of NDPH remain incompletely understood. This study aims to apply seed‐based analysis to explore the functional connectivity (FC) of brainstem nuclei in patients with NDPH using resting‐state functional magnetic resonance imaging (MRI). Methods: The FC analysis from the region of interest (ROI) to whole brain voxels was used to investigate 29 patients with NDPH and 37 well‐matched healthy controls (HCs) with 3.0 Tesla MRI. The 76 nuclei in the brainstem atlas were defined as ROIs. Furthermore, we explored the correlations between FC and patients' clinical characteristics and neuropsychological evaluations. Results: Patients with NDPH exhibited reduced FC in multiple brainstem nuclei compared to HCs (including right inferior medullary reticular formation, right mesencephalic reticular formation, bilateral locus coeruleus, bilateral laterodorsal tegmental nucleus‐central gray of the rhombencephalon, median raphe, left medial parabrachial nucleus, periaqueductal gray, and bilateral ventral tegmental area‐parabrachial pigmented nucleus complex) and increased FC in periaqueductal gray. No significant correlations were found between the FC of these brain regions and clinical characteristics or neuropsychological evaluations after Bonferroni correction (p > 0.00016). Conclusions: Our results demonstrated that patients with NDPH have abnormal FC of brainstem nuclei involved in the perception and regulation of pain and emotions. [ABSTRACT FROM AUTHOR]

Introduction: Cerebral malaria (CM) is a lethal neuroinflammatory disease caused by Plasmodium infection. Immune cells and brain parenchyma cells contribute to the pathogenesis of CM. However, a systematic examination of the changes that occur in the brain parenchyma region during CM at the single‐cell resolution is still poorly studied. Aims: To explore cell composition and CD8+ T cell infiltration, single‐cell RNA sequencing (scRNA‐seq) was performed on the brainstems of healthy and experimental cerebral malaria (ECM) mice. Then CD8+ T cell infiltration was confirmed by flow cytometry and immunofluorescence assays. Subsequently, the characteristics of the brain‐infiltrated CD8+ T cells were analyzed. Finally, the interactions between parenchyma cells and brain‐infiltrated CD8+ T cells were studied with an astrocytes‐CD8+ T cell cocultured model. Results: The brainstem is the most severely damaged site during ECM. ScRNA‐seq revealed a large number of CD8+ T cells infiltrating into the brainstem in ECM mice. Brain‐infiltrated CD8+ T cells were highly activated according to scRNA‐seq, immunofluorescence, and flow cytometry assays. Further analysis found a subset of ki‐67+ CD8+ T cells that have a higher transcriptional level of genes related to T cell function, activation, and proliferation, suggesting that they were exposed to specific antigens presented by brain parenchyma cells. Brain‐infiltrated CD8+ T cells were the only prominent source of IFN‐γ in this single‐cell analysis. Astrocytes, which have a high interferon response, act as cross‐presenting cells to recruit and re‐activate brain‐infiltrated CD8+ T cells. We also found that brain‐infiltrated CD8+ T cells were highly expressed immune checkpoint molecule PD‐1, while parenchyma cells showed up‐regulation of PD‐L1 after infection. Conclusions: These findings reveal a novel interaction between brain‐infiltrated CD8+ T cells and parenchyma cells in the ECM brainstem, suggesting that the PD‐1/PD‐L1 signal pathway is a promising adjunctive therapeutic strategy for ECM targeting over‐activated CD8+ T cells. [ABSTRACT FROM AUTHOR]

Purpose: Although the co‐occurrence of interstitial cystitis (IC) and endometriosis (ENDO) is remarkably high, the exact pathophysiology for this co‐occurrence is unknown. The convergence of the inputs from the involved structures to the same neuronal centers may suggest neuronal hyperexcitability as a mechanism for this co‐occurrence. Methods: The present study aimed to investigate the association between IC and ENDO, by studying the changes in brainstem responses to cystometry in a rat model of ENDO and cyclophosphamide (CYP)‐induced IC using c‐fos immunohistochemistry. Results: Following cystometry the brainstem areas that had significant increase in c‐fos expression in ENDO alone included: periaqueductal gray (PAG) nuclei, dorsal raphe nucleus, raphe obscurus nucleus, kolliker‐ Fuse areas, and area postrema. However, the brainstem areas that had increased significantly in the c‐fos expression in the ENDO and CYP treated animals included: gigantocellular nucleus, lateral paragigantocellular nucleus, caudoventrolateral nucleus, rostroventrolateral/caudoventrolateral nucleus, lateral reticular nucleus, locus coeruleus, lateral PAG, raphe pallidus nucleus, raphe magnus nucleus, rostroventrolateral nucleus, dorsal motor nucleus of vagus, and solitary tract nucleus. Whereas only lateral parabrachial nucleus showed significant increase in c‐fos expression in CYP treated animals alone. Conclusions: The results of the present study demonstrate the overlap of brainstem nuclei that are excited by urinary bladder under ENDO and IC conditions. The pattern of hyperexcitability of the brainstem nuclei may help in understating the pathophysiology of IC and ENDO conditions. [ABSTRACT FROM AUTHOR]

Although multiple theories have speculated about the brainstem reticular formation's involvement in autistic behaviors, the in vivo imaging of brainstem nuclei needed to test these theories has proven technologically challenging. Using methods to improve brainstem imaging in children, this study set out to elucidate the role of the autonomic, nociceptive, and limbic brainstem nuclei in the autism features of 145 children (74 autistic children, 6.0–10.9 years). Participants completed an assessment of core autism features and diffusion‐ and T1‐weighted imaging optimized to improve brainstem images. After data reduction via principal component analysis, correlational analyses examined associations among autism features and the microstructural properties of brainstem clusters. Independent replication was performed in 43 adolescents (24 autistic, 13.0–17.9 years). We found specific nuclei, most robustly the parvicellular reticular formation‐alpha (PCRtA) and to a lesser degree the lateral parabrachial nucleus (LPB) and ventral tegmental parabrachial pigmented complex (VTA‐PBP), to be associated with autism features. The PCRtA and some of the LPB associations were independently found in the replication sample, but the VTA‐PBP associations were not. Consistent with theoretical perspectives, the findings suggest that individual differences in pontine reticular formation nuclei contribute to the prominence of autistic features. Specifically, the PCRtA, a nucleus involved in mastication, digestion, and cardio‐respiration in animal models, was associated with social communication in children, while the LPB, a pain‐network nucleus, was associated with repetitive behaviors. These findings highlight the contributions of key autonomic brainstem nuclei to the expression of core autism features. Lay Summary: Looking at brain scans of 145 autistic and non‐autistic children and testing our results again in 45 autistic and non‐autistic adolescents, we found that a particular part of the brainstem thought to be involved in chewing, digesting food, heart rate, and breathing was related to social communication. Another part of the brainstem thought to be involved in processing painful sensations was associated with preferring things not to change and preferring to stick with certain routines. This information further supports the involvement of the brainstem in the expression of autism features. [ABSTRACT FROM AUTHOR]

11‐beta‐hydroxysteroid dehydrogenases (11β‐HSDs) catalyse the conversion of active 11‐hydroxy glucocorticoids (cortisol, corticosterone) and their inert 11‐keto forms (cortisone, 11‐dehydrocorticosterone). They were first reported in the body and brain 70 years ago, but only recently have they become of interest. 11β‐HSD2 is a dehydrogenase, potently inactivating glucocorticoids. In the kidney, 11β‐HSD2 generates the aldosterone‐specificity of intrinsically non‐selective mineralocorticoid receptors. 11β‐HSD2 also protects the developing foetal brain and body from premature glucocorticoid exposure, which otherwise engenders the programming of neuropsychiatric and cardio‐metabolic disease risks. In the adult CNS, 11β‐HSD2 is confined to a part of the brain stem where it generates aldosterone‐specific central control of salt appetite and perhaps blood pressure. 11β‐HSD1 is a reductase, amplifying active glucocorticoid levels within brain cells, notably in the cortex, hippocampus and amygdala, paralleling its metabolic functions in peripheral tissues. 11β‐HSD1 is elevated in the ageing rodent and, less certainly, human forebrain. Transgenic models show this rise contributes to age‐related cognitive decline, at least in mice. 11β‐HSD1 inhibition robustly improves memory in healthy and pathological ageing rodent models and is showing initial promising results in phase II studies of healthy elderly people. Larger trials are needed to confirm and clarify the magnitude of effect and define target populations. The next decade will be crucial in determining how this tale ends – in new treatments or disappointment. [ABSTRACT FROM AUTHOR]

Studies on brain anatomy can clarify specific evolutionary and behavioural aspects of wild animals. The rich diversity in a broad range of habitats makes carnivorans especially eligible for studying the relations between the brain form and behaviour, cognitive, sensorial and motor traits. This study compared the brain's contour and total and segmented brain volumetry in three species of neotropical carnivorans. CT images of 17 skulls of three species were acquired: Conepatus chinga (n = 6), Galictis cuja (n = 6) and Lontra longicaudis (n = 5). Three‐dimensional endocasts allowed for estimating the brain's total and segmented volumes (olfactory bulb, rostral cerebrum, caudal cerebrum and cerebellum/brain stem). The average volume percentage of the segments was compared interspecifically and intraspecifically between the sexes. The otter has a notably more complex gyrification, typical for semiaquatic carnivorans. Proportionally, the olfactory bulb was significantly larger in hog‐nosed skunks, possibly due to a better sense of smell for capturing insects. The proportional volumes of the rostral cerebrum, caudal cerebrum and cerebellum/brain stem segments did not differ between these species. Social behaviour traits and tactile, motor and balance skills were probably not sufficiently distinct to reflect differences in the brain segments analysed in these three species. [ABSTRACT FROM AUTHOR]

Purpose: Functional understanding of the periaqueductal gray (PAG), a clinically relevant brainstem region, can be advanced using 1H‐MRS. However, the PAG's small size and high levels of physiological noise are methodologically challenging. This study aimed to (1) improve 1H‐MRS quality in the PAG using spectral registration for frequency and phase error correction; (2) investigate whether spectral registration is particularly useful in cases of greater head motion; and (3) examine metabolite quantification using literature‐based or individual‐based water relaxation times. Methods: Spectra were acquired in 33 healthy volunteers (50.1 years, SD = 17.19, 18 females) on a 3 T Philipps MR system using a point‐resolved spectroscopy (PRESS) sequence optimized with very selective saturation pulses (OVERPRESS) and voxel‐based flip angle calibration (effective volume of interest size: 8.8 × 10.2 × 12.2 mm3). Spectra were fitted using LCModel and SNR, NAA peak linewidths and Cramér‐Rao lower bounds (CRLBs) were measured after spectral registration and after minimal frequency alignment. Results: Spectral registration improved SNR by 5% (p = 0.026, median value post‐correction: 18.0) and spectral linewidth by 23% (p < 0.001, 4.3 Hz), and reduced the metabolites' CRLBs by 1% to 15% (p < 0.026). Correlational analyses revealed smaller SNR improvements with greater head motion (p = 0.010) recorded using a markerless motion tracking system. Higher metabolite concentrations were detected using individual‐based compared to literature‐based water relaxation times (p < 0.001). Conclusion: This study demonstrates high‐quality 1H‐MRS acquisition in the PAG using spectral registration. This shows promise for future 1H‐MRS studies in the PAG and possibly other clinically relevant brain regions with similar methodological challenges. [ABSTRACT FROM AUTHOR]

Purpose: Obvious inconsistencies in auto‐segmentations exist among various AI software. In this study, we have developed a novel convolutional neural network (CNN) fine‐tuning workflow to achieve precise and robust localized segmentation. Methods: The datasets include Hubei Cancer Hospital dataset, Cetuximab Head and Neck Public Dataset, and Québec Public Dataset. Seven organs‐at‐risks (OARs), including brain stem, left parotid gland, esophagus, left optic nerve, optic chiasm, mandible, and pharyngeal constrictor, were selected. The auto‐segmentation results from four commercial AI software were first compared with the manual delineations. Then a new multi‐scale lightweight residual CNN model with an attention module (named as HN‐Net) was trained and tested on 40 samples and 10 samples from Hubei Cancer Hospital, respectively. To enhance the network's accuracy and generalization ability, the fine‐tuning workflow utilized an uncertainty estimation method for automatic selection of candidate samples of worthiness from Cetuximab Head and Neck Public Dataset for further training. The segmentation performances were evaluated on the Hubei Cancer Hospital dataset and/or the entire Québec Public Dataset. Results: A maximum difference of 0.13 and 0.7 mm in average Dice value and Hausdorff distance value for the seven OARs were observed by four AI software. The proposed HN‐Net achieved an average Dice value of 0.14 higher than that of the AI software, and it also outperformed other popular CNN models (HN‐Net: 0.79, U‐Net: 0.78, U‐Net++: 0.78, U‐Net‐Multi‐scale: 0.77, AI software: 0.65). Additionally, the HN‐Net fine‐tuning workflow by using the local datasets and external public datasets further improved the automatic segmentation with the average Dice value by 0.02. Conclusion: The delineations of commercial AI software need to be carefully reviewed, and localized further training is necessary for clinical practice. The proposed fine‐tuning workflow could be feasibly adopted to implement an accurate and robust auto‐segmentation model by using local datasets and external public datasets. [ABSTRACT FROM AUTHOR]

A 61-year-old man with stroke risk factors presented with symptoms that initially suggested a brainstem stroke. However, his condition rapidly worsened, and he developed symptoms consistent with Miller Fisher syndrome. Further investigation revealed that he had consumed contaminated almond milk, leading to a diagnosis of botulism. The patient was treated with antitoxin and eventually recovered after months of hospitalization. This case highlights the challenges in diagnosing botulism and emphasizes the importance of timely administration of antitoxin. [Extracted from the article]

Background: To explore the altered functional connectivity (FC) of the nucleus tractus solitarii (NTS) in patients with chronic cough after lung surgery using resting‐state functional magnetic resonance imaging (rs‐fMRI), and the association between abnormal FC and clinical scale scores. Methods: A total of 22 patients with chronic cough after lung surgery and 22 healthy controls were included. Visual analog scale (VAS), Mandarin Chinese version of the Leicester Cough Questionnaire (LCQ‐MC), and Hamilton anxiety rating scale (HAMA) scores were assessed, and rs‐fMRI data were collected. The FC analysis was performed using the NTS as the seed point, and FC values with all voxels in the whole brain were calculated. A two‐sample t‐test was used to compare FC differences between the two groups. The FC values of brain regions with differences were extracted and correlated with clinical scale scores. Results: In comparison to healthy controls, FC values in the NTS and anterior cingulate cortex(ACC) were reduced in patients with chronic cough after lung surgery (GRF correction, p‐voxel < 0.005, p‐cluster < 0.05) which were positively correlated with LCQ‐MC scores (r = 0.534, p = 0.011), but with VAS (r = −0.500, p = 0.018), HAMA (r = −0.713, p < 0.001) scores were negatively correlated. Conclusions: Reduced FC of the NTS with ACC may be associated with cough hypersensitivity and may contribute to anxiety in patients with chronic cough after lung surgery. [ABSTRACT FROM AUTHOR]

Background: Inaccurate manual organ delineation is one of the high‐risk failure modes in radiation treatment. Numerous automated contour quality assurance (QA) systems have been developed to assess contour acceptability; however, manual inspection of flagged cases is a time‐consuming and challenging process, and can lead to users overlooking the exact error location. Purpose: Our aim is to develop and validate a contour QA system that can effectively detect and visualize subregional contour errors, both qualitatively and quantitatively. Methods/Materials: A novel contour subregion error detection (CSED) system was developed using subregional surface distance discrepancies between manual and deep learning auto‐segmentation (DLAS) contours. A validation study was conducted using a head and neck public dataset containing 339 cases and evaluated according to knowledge‐based pass criteria derived from a clinical training dataset of 60 cases. A blind qualitative evaluation was conducted, comparing the results from the CSED system with manual labels. Subsequently, the CSED‐flagged cases were re‐examined by a radiation oncologist. Results: The CSED system could visualize the diverse types of subregional contour errors qualitatively and quantitatively. In the validation dataset, the CSED system resulted in true positive rates (TPR) of 0.814, 0.800, and 0.771; false positive rates (FPR) of 0.310, 0.267, and 0.298; and accuracies of 0.735, 0.759, and 0.730, for brainstem and left and right parotid contours, respectively. The CSED‐assisted manual review caught 13 brainstem, 19 left parotid, and 21 right parotid contour errors missed by conventional human review. The TPR/FPR/accuracy of the CSED‐assisted manual review improved to 0.836/0.253/0.784, 0.831/0.171/0.830, and 0.808/0.193/0.807 for each structure, respectively. Further, the time savings achieved through CSED‐assisted review improved by 75%, with the time for review taking 24.81 ± 12.84, 26.75 ± 10.41, and 28.71 ± 13.72 s for each structure, respectively. Conclusions: The CSED system enables qualitative and quantitative detection, localization, and visualization of manual segmentation subregional errors utilizing DLAS contours as references. The use of this system has been shown to help reduce the risk of high‐risk failure modes resulting from inaccurate organ segmentation. [ABSTRACT FROM AUTHOR]

A monosynaptic pathway connects the substantia nigra pars compacta (SNpc) to neurons of the dorsal motor nucleus of the vagus (DMV). This monosynaptic pathway modulates the vagal control of gastric motility. It is not known, however, whether this nigro‐vagal pathway also modulates the tone and motility of the proximal colon. In rats, microinjection of retrograde tracers in the proximal colon and of anterograde tracers in SNpc showed that bilaterally labelled colonic‐projecting neurons in the DMV received inputs from SNpc neurons. Microinjections of the ionotropic glutamate receptor agonist, NMDA, in the SNpc increased proximal colonic motility and tone, as measured via a strain gauge aligned with the colonic circular smooth muscle; the motility increase was inhibited by acute subdiaphragmatic vagotomy. Upon transfection of SNpc with pAAV‐hSyn‐hM3D(Gq)‐mCherry, chemogenetic activation of nigro‐vagal nerve terminals by brainstem application of clozapine‐N‐oxide increased the firing rate of DMV neurons and proximal colon motility; both responses were abolished by brainstem pretreatment with the dopaminergic D1‐like antagonist SCH23390. Chemogenetic inhibition of nigro‐vagal nerve terminals following SNpc transfection with pAAV‐hSyn‐hM4D(Gi)‐mCherry decreased the firing rate of DMV neurons and inhibited proximal colon motility. These data suggest that a nigro‐vagal pathway modulates activity of the proximal colon motility tonically via a discrete dopaminergic synapse in a manner dependent on vagal efferent nerve activity. Impairment of this nigro‐vagal pathway may contribute to the severely reduced colonic transit and prominent constipation observed in both patients and animal models of parkinsonism. Key points: Substantia nigra pars compacta (SNpc) neurons are connected to the dorsal motor nucleus of the vagus (DMV) neurons via a presumed direct pathway.Brainstem neurons in the lateral DMV innervate the proximal colon. Colonic‐projecting DMV neurons receive inputs from neurons of the SNpc.The nigro‐vagal pathway modulates tone and motility of the proximal colon via D1‐like receptors in the DMV.The present study provides the mechanistic basis for explaining how SNpc alterations may lead to a high rate of constipation in patients with Parkinson's Disease. [ABSTRACT FROM AUTHOR]

Bi‐allelic variants in peroxiredoxin 3 (PRDX3) have only recently been associated with autosomal recessive spinocerebellar ataxia characterized by early onset slowly progressive cerebellar ataxia, variably associated with hyperkinetic and hypokinetic features, accompanied by cerebellar atrophy and occasional olivary and brainstem involvement. Herein, we describe a further simplex case carrying a reported PRDX3 variant as well as two additional cases with novel variants. We report the first Brazilian patient with SCAR32, replicating the pathogenic status of a known variant. All presented cases from the Brazilian and Indian populations expand the phenotypic spectrum of the disease by displaying prominent neuroradiological findings. SCAR32, although rare, should be included in the differential diagnosis of sporadic or recessive childhood and adolescent‐onset pure and complex cerebellar ataxia. [ABSTRACT FROM AUTHOR]

The fourth ventricle is a small, fluid‐filled cavity located within the brain that plays a vital role in the body's physiological functions. Therefore, the anatomical elements forming it bear significant clinical relevance. However, the exact relations between the elements that form its roof are still debated in the neuroanatomical literature; the inferior medullary velum, and the ventricle's median aperture in particular. In some atlases, the inferior medullary velum is placed in the midline, while in others, it is placed in the transverse plane. The median aperture is also displayed in different ways in midsagittal drawings: as a round perforation of a midline velum, as a foramen in an uncharacterized part of the ventricle, and as a gap between the nodule and the brainstem. This work aims to provide a comprehensive review of the different descriptions of the fourth ventricle, in order to gain a clearer understanding of the ventricular system's structure. [ABSTRACT FROM AUTHOR]

A commentary published in the Journal of Diabetes Investigation discusses the role of GIPR neurons in the hypothalamus and brainstem in regulating feeding and weight. The study found that activating these neurons resulted in different feeding and behavior responses. The study suggests that these pathways work together to reduce feeding and bodyweight. The article also explores the effects of GLP-1RA and GIPRA on bodyweight and food intake in mice, and suggests that GIPRA may have a role in controlling feeding and bodyweight. However, more research is needed to understand the safety and potential side effects of GIPR/GLP-1R coagonism. [Extracted from the article]

Background: Pre‐clinical ultra‐high dose rate (UHDR) electron irradiations on time scales of 100 ms have demonstrated a remarkable sparing of brain and lung tissues while retaining tumor efficacy when compared to conventional dose rate irradiations. While clinically‐used gantries and intensity modulation techniques are too slow to match such time scales, novel very‐high energy electron (VHEE, 50–250 MeV) radiotherapy (RT) devices using 3D‐conformed broad VHEE beams are designed to deliver UHDR treatments that fulfill these timing requirements. Purpose: To assess the dosimetric plan quality obtained using VHEE‐based 3D‐conformal RT (3D‐CRT) for treatments of glioblastoma and lung cancer patients and compare the resulting treatment plans to those delivered by standard‐of‐care intensity modulated photon RT (IMRT) techniques. Methods: Seven glioblastoma patients and seven lung cancer patients were planned with VHEE‐based 3D‐CRT using 3 to 16 coplanar beams with equidistant angular spacing and energies of 100 and 200 MeV using a forward planning approach. Dose distributions, dose‐volume histograms, coverage (V95%) and homogeneity (HI98%) for the planning target volume (PTV), as well as near‐maximum doses (D2%) and mean doses (Dmean) for organs‐at‐risk (OAR) were evaluated and compared to clinical IMRT plans. Results: Mean differences of V95% and HI98% of all VHEE plans were within 2% or better of the IMRT reference plans. Glioblastoma plan dose metrics obtained with VHEE configurations of 200 MeV and 3–16 beams were either not significantly different or were significantly improved compared to the clinical IMRT reference plans. All OAR plan dose metrics evaluated for VHEE plans created using 5 beams of 100 MeV were either not significantly different or within 3% on average, except for Dmean for the body, Dmean for the brain, D2% for the brain stem, and D2% for the chiasm, which were significantly increased by 1, 2, 6, and 8 Gy, respectively (however below clinical constraints). Similarly, the dose metrics for lung cancer patients were also either not significantly different or were significantly improved compared to the reference plans for VHEE configurations with 200 MeV and 5 to 16 beams with the exception of D2% and Dmean to the spinal canal (however below clinical constraints). For the lung cancer cases, the VHEE configurations using 100 MeV or only 3 beams resulted in significantly worse dose metrics for some OAR. Differences in dose metrics were, however, strongly patient‐specific and similar for some patient cases. Conclusions: VHEE‐based 3D‐CRT may deliver conformal treatments to simple, mostly convex target shapes in the brain and the thorax with a limited number of critical adjacent OAR using a limited number of beams (as low as 3 to 7). Using such treatment techniques, a dosimetric plan quality comparable to that of standard‐of‐care IMRT can be achieved. Hence, from a treatment planning perspective, 3D‐conformal UHDR VHEE treatments delivered on time scales of 100 ms represent a promising candidate technique for the clinical transfer of the FLASH effect. [ABSTRACT FROM AUTHOR]

This case series compared clinical variables and various combinations of immunotherapy received with outcomes of patients with severe acute necrotizing encephalopathy (ANE). We performed a retrospective review of clinical variables, immunotherapy received, and outcomes (based on the modified Rankin Scale) in Malaysia between February 2019 and January 2020. Twenty‐seven children (12 male), aged 7 months to 14 years (mean 4 years) at diagnosis were included. Of these, 23 had an ANE severity score of 5 to 9 out of 9 (high risk). Eleven patients received tocilizumab (four in combination with methylprednisolone [MTP], seven with MTP + intravenous immunoglobulin [IVIG]) and 16 did not (two received MTP alone, 14 received MTP + IVIG). Nine died. Among the survivors, six had good outcomes (modified Rankin Score 0–2) at 6 months follow‐up. All patients who received tocilizumab in combination with MTP + IVIG survived. Twenty children received first immunotherapy within 48 hours of admission. No significant association was found between the timing of first immunotherapy with outcomes. Those with brainstem dysfunction (p = 0.016) were observed to have poorer outcomes. This study showed a trend towards better survival when those with severe ANE were treated with tocilizumab in combination with MTP + IVIG. However, larger studies will be needed to determine the effect of this regime on the long‐term outcomes. [ABSTRACT FROM AUTHOR]

Background: The trigeminal vascular system is an important part of the anatomical and physiological basis of migraine. The effective connectivity (EC) among the regions of interest (ROIs) in the trigeminal vascular system involved in migraine without aura (MWoA) remains unclear. Methods: In this cross‐sectional study, 48 patients (mean [SD] age 38.06 [10.35] years; male, 14/48 [29%]) with MWoA during the interictal phase and 48 healthy controls of similar age and sex (mean [SD] age 38.96 [10.96] years; male, 14/48 [29%]) underwent resting‐state functional magnetic resonance imaging (fMRI). Dynamic causal modeling analysis was conducted to investigate directional EC among ROIs in the trigeminal vascular system including the bilateral brainstem, the primary somatosensory cortex (S1), the thalamus, and the insula. Results: Compared with the healthy control group, MWoA represented significantly reduced EC from the left brainstem (Brainstem.L) to the left insula (MWoA: mean [SD] −0.16 [0.36]; healthy controls: mean [SD] 0.11 [0.41]; Pcorrected = 0.021), reduced EC from the Brainstem.L to the right insula (MWoA: mean [SD] −0.15 [0.39]; healthy controls: mean [SD] 0.03 [0.35]; Pcorrected = 0.021), and decreased EC from the left thalamus (Thalamus.L) to the Brainstem.L (MWoA: mean [SD] −0.13 [0.56]; healthy controls: mean [SD] 0.10 [0.45]; Pcorrected = 0.021). Altered EC parameters were not significantly correlated with MWoA clinical data. Conclusion: These results further provide increasing evidence that disturbed homeostasis of the trigeminovascular nociceptive pathway is involved in the pathophysiological mechanisms of migraine. Patients with MWoA exhibited a regional interaction distinct from healthy controls in the neural pathway of the Bilateral Insula–Brainstem.L–Thalamus.L, which may shed light on the future understanding of brain mechanisms for MWoA. Future brain‐based interventions are suggested to consider the dysregulation in the Bilateral Insula–Brainstem.L–Thalamus.L circuits. [ABSTRACT FROM AUTHOR]

(B) mRNA expression of select immunoglobulin chain genes (detected at highest abundance in LC-MS/MS data) in a cohort of 153 pediatric CNS lesions. (A) Most abundant proteins detected by LC-MS/MS analysis of the LHCDD - number of proteins compared with the total spectrum count. Our patient sample is highlighted in red. (C) Ingenuity pathway analysis pathway analysis showed elevated immune pathways with a positive Z score, confirming the findings from LC-MS/MS. Keywords: aggregoma; genomic profiling; immunoglobulin kappa-chains; light and heavy chain deposition disease; mass spectrometry EN aggregoma genomic profiling immunoglobulin kappa-chains light and heavy chain deposition disease mass spectrometry 1 5 5 09/01/23 20230901 NES 230901 Monoclonal immunoglobulin (Ig) deposition diseases are classified as heavy chain deposition disease (HCDD); light chain deposition diseases (LCDD); and light and heavy chain deposition disease (LHCDD) - deposits of both light [kappa ( ) and lambda ( )], and heavy [alpha ( ), delta ( ), epsilon ( ), gamma ( ), and mu ( )] Ig chains. [Extracted from the article]

Brain health is the humans' primary goal in achieving health and longevity. Brainstem glioma (BSG) has a high disability and mortality rate, posing a serious threat to children's brain health. Delivery of drugs to the brainstem is limited by poor tumor targeting and low blood‐brain barrier (BBB) permeability. Thus, it is a great challenge to construct intracranial drug delivery systems with strong biocompatibility, low immunogenicity, and high BBB permeability for the delivery of drugs targeting BSG. Exosomes, as the next generation of novel delivery systems, have been widely used to across the BBB due to their advantages of good biocompatibility, stability, and permeability of the BBB and have made corresponding breakthroughs in targeted drug delivery for CNS diseases. This review summarizes natural, polypeptide functionalized, and physical methods‐assisted brain‐targeted exosomes‐based drug delivery systems, the drug treatment bottleneck of BSG, and highlights the potential of using a brain‐targeted exosomes‐based drug delivery system to overcome the drug treatment bottleneck of BSG. It provides new insights into using exosomes‐based drug delivery for BSG treatment. [ABSTRACT FROM AUTHOR]

Background: Stereotactic radiosurgery (SRS) relies on small fields to ablate lesions. Currently, linac based treatment is delivered via circular cones using a 6 MV beam. There is interest in both lower energy photon beams, which can offer steeper dose fall off as well as higher energy photon beams, which have higher dose rates, thus reducing radiation delivery times. Of interest in this study is the 2.5 MV beam developed for imaging applications and both the 6 and 10 MV flattening‐filter‐free (FFF) beams, which can achieve dose rates up to 2400 cGy/min. Purpose: This study aims to assess the benefit and feasibility among different energy beams ranging from 2.5 to 10 MV beams by evaluating the dosimetric effects of each beam and comparing the dose to organs‐at‐risk (OARs) for two separate patient plans. One based on a typical real patient tremor utilizing a 4 mm cone and the other a typical brain metastasis delivered with a 10 mm cone. Methods: The Monte Carlo codes BEAMnrc/DOSXYZnrc were used to generate beams of 2.5 MV, 6 MV‐FFF, 6 MV‐SRS, 6 MV, 10 MV‐FFF, and 10 MV from a Varian TrueBeam except 6 MV‐SRS, which is taken from a Varian TX model linear accelerator. Each beam's energy spectrum, mean energy, %dd curve, and dose profile were obtained by analyzing the simulated beams. Calculated patient dose distributions were compared among six different energy beam configurations based on a realistic treatment plan for thalamotomy and a conventional brain metastasis plan. Dose to OARs were evaluated using dose–volume histograms for the same target dose coverage. Results: The mean energies of photons within the primary beam projected area were insensitive to cone sizes and the values of percentage depth–dose curves (%dd) at d = 5 cm and SSD = 95 cm for a 4 mm (10 mm) cone ranges from 62.6 (64.4) to 82.2 (85.7) for beam energy ranging from 2.5 to 10 MV beams, respectively. Doses to OARs were evaluated among these beams based on real treatment plans delivering 15 000 and 2200 cGy to the target with a 4 and 10 mm cone, respectively. The maximum doses to the brainstem, which is 10 mm away from the isocenter, was found to be 434 (300), 632 (352), 691 (362), 733 (375), 822 (403), and 975 (441) cGy for 2.5 MV, 6 MV‐FFF, 6 MV‐SRS, 6 MV, 10 MV‐FFF, and 10 MV beams delivering 15 000 (2200) cGy target dose, respectively. Conclusion: Using the 6 MV‐SRS as reference, changes of the maximum dose (691 cGy) to the brain stem are −37%, −9%, +6%, +19%, and 41% for 2.5 MV, 6 MV‐FFF, 6 MV, 10 MV‐FFF, and 10 MV beams, respectively, based on the thalamotomy plan, where the "‐" or "+" signs indicate the percentage decrease or increase. Changes of the maximum dose (362 cGy) to brain stem, based on the brain metastasis plan are much less for respective beam energies. The sum of 21 arcs beam‐on time was 39 min on our 6 MV‐SRS beam with 1000 cGy/min for thalamotomy. The beam‐on time can be reduced to 16 min with 10 MV‐FFF. [ABSTRACT FROM AUTHOR]

Outer radial glial cells (oRGs) give rise to neurons and glial cells and contribute to cell migration and expansion in developing neocortex. HOPX has been described as a marker of oRGs and possible actor in glioblastomas. Recent years' evidence points to spatiotemporal differences in brain development which may have implications for the classification of cell types in the central nervous system and understanding of a range of neurological diseases. Using the Human Embryonic/Fetal Biobank, Institute of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark, HOPX and BLBP immunoexpression was investigated in developing frontal, parietal, temporal and occipital human neocortex, other cortical areas and brain stem regions to interrogate oRG and HOPX regional heterogeneity. Furthermore, usage of high‐plex spatial profiling (Nanostring GeoMx® DSP) was tested on the same material. HOPX marked oRGs in several human developing brain regions as well as cells in known gliogenic areas but did not completely overlap with BLBP or GFAP. Interestingly, limbic structures (e.g. olfactory bulb, indusium griseum, entorhinal cortex, fimbria) showed more intense HOPX immunoreactivity than adjacent neocortex and in cerebellum and brain stem, HOPX and BLBP seemed to stain different cell populations in cerebellar cortex and corpus pontobulbare. DSP screening of corresponding regions indicated differences in cell type composition, vessel density and presence of apolipoproteins within and across regions and thereby confirming the importance of acknowledging time and place in developmental neuroscience. [ABSTRACT FROM AUTHOR]

A study published in the Journal of Magnetic Resonance Imaging explores the potential of using multi-shell diffusion MRI metrics to predict H3K27M mutations in brainstem gliomas. These mutations are important to understand in neuro-oncology, but large-scale radiogenomics studies on histone-altered gliomas are limited due to their rarity. The study found significant differences in diffusion metrics between H3K27M-altered and wild-type brainstem gliomas, suggesting increased tumor malignancy in the altered group. The study also suggests that age and intracellular volume fraction could predict the mutation status, with higher accuracy in the pediatric group. However, further validation and studies are needed before these findings can be applied clinically. [Extracted from the article]

This article discusses a case study of a 54-year-old female patient with a history of hypertension who presented with left-sided weakness and slurred speech. The patient was diagnosed with an acute ischemic stroke and received antiplatelet therapy. Further investigations revealed a subclavian artery web, a rare condition that can lead to thrombosis and embolic stroke. The case highlights the importance of multiplanar reconstructions in accurately diagnosing arterial webs. The patient remained stroke-free during a 1.5-year follow-up period. [Extracted from the article]