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Glossopharyngeal neuralgia due to vertebrobasilar dolichoectasia is a rare form of neuropathic pain, and presents diagnostic and therapeutic challenges. Clinical presentation: A 67-yearold man presented with severe burning pain in the left oral cavity, with no explanatory findings during dental and ear, nose, and throat evaluations. Temporomandibular joint examination revealed tenderness, and panoramic radiographs showed a noncontributory periapical radiolucency. Magnetic resonance imaging/magnetic resonance angiography revealed abnormally tortuous vertebral arteries compressing the glossopharyngeal nerves and the brainstem. Topical lidocaine reduced pain, confirming glossopharyngeal neuralgia. Carbamazepine was initially ineffective, but at 200 mg pain reduced from 90 to 20 on the visual analog scale. The patient requested and underwent microvascular decompression surgery, which eliminated his pain. Conclusion: When the vertebral artery compresses the glossopharyngeal nerve, the pain is more intense, attributed to its thicker vascular structure. Local anesthetic testing aids in identifying glossopharyngeal neuralgia. Dental practitioners must be skilled in diagnostics and possess anatomical knowledge for accurate evaluation and referral of throat and ear pain. [ABSTRACT FROM AUTHOR]

Inherited deficiency of the RNA lariat-debranching enzyme 1 (DBR1) is a rare etiology of brainstem viral encephalitis. The cellular basis of disease and the range of viral predisposition are unclear. We report inherited DBR1 deficiency in a 14-year-old boy who suffered from isolated SARS-CoV-2 brainstem encephalitis. The patient is homozygous for a previously reported hypomorphic and pathogenic DBR1 variant (I120T). Consistently, DBR1 I120T/I120T fibroblasts from affected individuals from this and another unrelated kindred have similarly low levels of DBR1 protein and high levels of RNA lariats. DBR1 I120T/I120T human pluripotent stem cell (hPSC)-derived hindbrain neurons are highly susceptible to SARS-CoV-2 infection. Exogenous WT DBR1 expression in DBR1 I120T/I120T fibroblasts and hindbrain neurons rescued the RNA lariat accumulation phenotype. Moreover, expression of exogenous RNA lariats, mimicking DBR1 deficiency, increased the susceptibility of WT hindbrain neurons to SARS-CoV-2 infection. Inborn errors of DBR1 impair hindbrain neuron-intrinsic antiviral immunity, predisposing to viral infections of the brainstem, including that by SARS-CoV-2.

Taurine is a conditionally essential micronutrient and one of the most abundant amino acids in humans1-3. In endogenous taurine metabolism, dedicated enzymes are involved in the biosynthesis of taurine from cysteine and in the downstream metabolism of secondary taurine metabolites4,5. One taurine metabolite is N-acetyltaurine6. Levels of N-acetyltaurine are dynamically regulated by stimuli that alter taurine or acetate flux, including endurance exercise7, dietary taurine supplementation8 and alcohol consumption6,9. So far, the identities of the enzymes involved in N-acetyltaurine metabolism, and the potential functions of N-acetyltaurine itself, have remained unknown. Here we show that the body mass index associated orphan enzyme phosphotriesterase-related (PTER)10 is a physiological N-acetyltaurine hydrolase. In vitro, PTER catalyses the hydrolysis of N-acetyltaurine to taurine and acetate. In mice, PTER is expressed in the kidney, liver and brainstem. Genetic ablation of Pter in mice results in complete loss of tissue N-acetyltaurine hydrolysis activity and a systemic increase in N-acetyltaurine levels. After stimuli that increase taurine levels, Pter knockout mice exhibit reduced food intake, resistance to diet-induced obesity and improved glucose homeostasis. Administration of N-acetyltaurine to obese wild-type mice also reduces food intake and body weight in a GFRAL-dependent manner. These data place PTER into a central enzymatic node of secondary taurine metabolism and uncover a role for PTER and N-acetyltaurine in body weight control and energy balance.

Exaggerated airway constriction triggered by repeated exposure to allergen, also called hyperreactivity, is a hallmark of asthma. Whereas vagal sensory neurons are known to function in allergen-induced hyperreactivity1-3, the identity of downstream nodes remains poorly understood. Here we mapped a full allergen circuit from the lung to the brainstem and back to the lung. Repeated exposure of mice to inhaled allergen activated the nuclei of solitary tract (nTS) neurons in a mast cell-, interleukin-4 (IL-4)- and vagal nerve-dependent manner. Single-nucleus RNA sequencing, followed by RNAscope assay at baseline and allergen challenges, showed that a Dbh+ nTS population is preferentially activated. Ablation or chemogenetic inactivation of Dbh+ nTS neurons blunted hyperreactivity whereas chemogenetic activation promoted it. Viral tracing indicated that Dbh+ nTS neurons project to the nucleus ambiguus (NA) and that NA neurons are necessary and sufficient to relay allergen signals to postganglionic neurons that directly drive airway constriction. Delivery of noradrenaline antagonists to the NA blunted hyperreactivity, suggesting noradrenaline as the transmitter between Dbh+ nTS and NA. Together, these findings provide molecular, anatomical and functional definitions of key nodes of a canonical allergen response circuit. This knowledge informs how neural modulation could be used to control allergen-induced airway hyperreactivity.

Chronic neuropathic pain can result from nervous system injury and can persist in the absence of external stimuli. Although ongoing pain characterizes the disorder, in many individuals, the intensity of this ongoing pain fluctuates dramatically. Previously, it was identified that functional magnetic resonance imaging signal covariations between the midbrain periaqueductal gray (PAG) matter, rostral ventromedial medulla (RVM), and spinal trigeminal nucleus are associated with moment-to-moment fluctuations in pain intensity in individuals with painful trigeminal neuropathy (PTN). Since this brainstem circuit is modulated by higher brain input, we sought to determine which cortical sites might be influencing this brainstem network during spontaneous fluctuations in pain intensity. Over 12 min, we recorded the ongoing pain intensity in 24 PTN participants and classified them as fluctuating (n = 13) or stable (n = 11). Using a PAG seed, we identified connections between the PAG and emotional-affective sites such as the hippocampal and posterior cingulate cortices, the sensory-discriminative posterior insula, and cognitive-affective sites such as the dorsolateral prefrontal (dlPFC) and subgenual anterior cingulate cortices that were altered dependent on spontaneous high and low pain intensity. Additionally, sliding-window functional connectivity analysis revealed that the dlPFC-PAG connection anticorrelated with perceived pain intensity over the entire 12 min period. These findings reveal cortical systems underlying moment-to-moment changes in perceived pain in PTN, which likely cause dysregulation in the brainstem circuits previously identified, and consequently alter the appraisal of pain across time.

Background and aimsThe precise roles of screen media activity (SMA) and sleep problems in relation to child/adolescent psychopathology remain ambiguous. We investigated temporal relationships among sleep problems, SMA, and psychopathology and potential involvement of thalamus-prefrontal-cortex (PFC)-brainstem structural covariation.MethodsThis study utilized data from the Adolescent Brain Cognitive Development study (n = 4,641 ages 9-12) at baseline, Year1, and Year2 follow-up. Cross-Lagged Panel Models (CLPMs) investigated reciprocal predictive relationships between sleep duration/problems, SMA, and psychopathology symptoms. A potential mediating role of baseline Thalamus-PFC-brainstem covariation on SMA-externalizing relationships was examined.ResultsParticipants were divided into discovery (n = 2,359, 1,054 girls) and replication (n = 2,282, 997 girls) sets. CLPMs showed 1) bidirectional associations between sleep duration and SMA in late childhood, with higher frequency SMA predicting shorter sleep duration (β = -0.10 [95%CI: -0.16, -0.03], p = 0.004) and vice versa (β = -0.11 [95%CI: -0.18, -0.05], p < 0.001); 2) externalizing symptoms at age 10-11 predicting sleep problems (β = 0.11 [95%CI: 0.04, 0.19], p = 0.002), SMA (β = 0.07 [95%CI: 0.01, 0.13], p = 0.014), and internalizing symptoms (β = 0.09 [95%CI: 0.05, 0.13], p < 0.001) at age 11-12; and 3) externalizing behavior at age 10-11 partially mediating the relationship between baseline thalamus-PFC-brainstem covariation and SMA at age 11-12 (indirect effect = 0.032 [95%CI: 0.003, 0.067], p-value = 0.030). Findings were replicable.ConclusionWe found bi-directional SMA-sleep-duration associations in late childhood. Externalizing symptoms preceded future SMA and sleep disturbances and partially mediated relationships between structural brain covariation and SMA. The findings emphasize the need for understanding individual differences and developing and implementing integrated strategies addressing both sleep concerns and screen time to mitigate potential impacts on psychopathology.

Somatic and sympathetic tones fluctuate together seamlessly across daily behaviors. In this issue of Cell, Zhang et al. describe populations of spinal projecting neurons in the rostral ventromedial medulla (rVMM) that harmonize somatic motor function and sympathetic activation. The coordinated regulation plays a vital role in supporting behaviors associated with various arousal states.

The relationship between heart failure and diabetes is intricate and bidirectional. Individuals with diabetes face an elevated risk of developing heart failure due to factors like insulin resistance, chronic inflammation, and metabolic irregularities. Elevated blood sugar levels can harm blood vessels and nerves, culminating in the buildup of fatty deposits in arteries, atherosclerosis, and hypertension, which significantly contribute to heart failure. Furthermore, diabetes can adversely impact the structure and function of the heart muscle, impairing its pumping capacity. Conversely, heart failure can also contribute to the onset of diabetes by disrupting the bodys metabolic processes and amplifying insulin resistance. The complex interaction between these conditions mandates a comprehensive approach to managing individuals with both diabetes and heart failure, underscoring the importance of addressing both aspects for enhanced patient outcomes. Although existing pharmacological treatments are limited and frequently associated with undesirable side effects, acupuncture has established itself as a traditional practice with a legacy. It remains a supplementary option for treating cardiovascular diseases. Heart failure and diabetes are both heavily associated with chronic upregulation of the sympathetic nervous system, which has been identified as a pivotal factor in the progression of disease. Mechanistic interplays such as the attenuation of central nitric oxide signaling may interfere with the production or availability of nitric oxide in key areas of the central nervous system, including the brainstem and hypothalamus. This review will delve into the current understanding of acupuncture on the autonomic nervous system and offer insights into its potential role in the future treatment landscape for diabetes and heart failure.

• MSG specifically activates neurons in the area postrema. • MSG induces neuronal necrosis and/or apoptosis and decreases neuronal density. • Microglial activation and phagocytosis occur after MSG treatment. • Neuronal density returns to normal with neurogenesis after MSG treatment. Neural stem cells and/or progenitor cells (NSCs/NPCs) in the subventricular and subgranular zones of the adult mammal forebrain generate new neurons and are involved in partial repair after injury. Recently, NSCs/NPCs were identified in the area postrema (AP) of the medulla oblongata of the hindbrain. In this study, we used the properties of fenestrate capillaries to observe specific neuronal elimination in the AP of adult mice and investigated subsequent neuronal regeneration by neurogenesis. Subcutaneous administration of monosodium glutamate (MSG) induced prominent Fos expression in HuC/D+ neurons in the AP 2 h after administration. MSG administration caused a marked decrease in HuC/D+ neuronal density by neuronal death 3 to 21 days after administration, which recovered to the control level 35 days later. After MSG administration, the density of TUNEL+ dying neurons and phagocytic microglia surrounding or engulfing neurons increased. Within 7 days of MSG administration, the number of BrdU+ Sox2+ and BrdU+ Math1+ cells increased markedly, and at least the BrdU+ Math1+ cells similarly increased for the next following 7 days. A remarkable number of HuC/D+ neurons with BrdU+ nuclei were observed 35 days after MSG administration. This study reveals that neurogenesis occurs in the AP of adult mice, recovering and maintaining normal neuronal density after neuronal death. [ABSTRACT FROM AUTHOR]

A general belief exists that tissue from anatomical donors, especially from the central nervous system (CNS), may not be suitable for histological investigation. This is based on the idea that fixation routinely used in embalming whilst optimal for enabling dissection, insufficiently preserves tissue architecture at the cellular level. However, anatomical donors represent a precious resource for microscopical investigation, provided that preservation is sufficient to enable recognition of structures at the histological level. This could considerably extend the biomedical knowledge currently gained from donations. In this study, we addressed this question and examined histologically, samples of medulla and spinal cord from donors from the Anatomical Gift Programme of RCSI in Dublin. Samples of medulla and spinal cord in the cervical, thoracic and lumbar regions were obtained with appropriate permissions from four different donors that had been previously embalmed for routine anatomical examination. The tissue obtained was processed for paraffin embedding and routine histology. Analysis revealed that several features were identifiable with good histological detail. A scoring system was applied to evaluate the level of histological preservation in the various samples by assessing the following parameters: tissue integrity, presence of leptomeninges along the entire section surface, distinction/adherence grey/white matter, identification of neurons, other cell nuclei, neuropil pattern, capillaries and other intraneural vessels. Lumbar spinal cord and to a lesser extent medulla and cervical spinal cord showed on average good quality of preservation. Conversely, thoracic spinal cord tended, in general, to be less well preserved. We can conclude that spinal cord and medulla samples from embalmed donors can be suitable for histological examination. These findings open new avenues of study of spinal cord and brain stem anatomy on cadaveric tissue from donors already existing in anatomy donation programmes. These results also pave the way for the potential development of new human models of study useful to spinal cord and brain stem researchers. Finally, this expands considerably the impact of the generosity of anatomical donors for the advancement of biomedical knowledge. [ABSTRACT FROM AUTHOR]

Purpose: This review article aimed to obtain an understanding of the positive outcomes and challenges associated with the use of simulation-based approaches for teaching communication and counseling skills in clinical education in audiology as described in the literature. Method: A scoping review was conducted during October 2023 to identify published journal articles that described how simulation-based approaches were used for teaching or assessing communication and/or counseling skills among audiology students. Database searches yielded 208 articles initially. Following abstract screening and full-text review, 17 articles were included for analysis. Results: Most studies focused on using simulation-based approaches for teaching, and there was a stronger focus on pediatric audiology. Most studies involved the use of standardized patients, with data collected via quantitative approaches using rating scales and surveys. Simulation-based approaches can offer positive learning experiences and practice opportunities for students acquiring communication and counseling skills. However, the benefits of simulation over traditional methods are unclear. Students may struggle to integrate technical and communication skills in simulated learning experiences. Conclusions: Engaging with simulation-based approaches may provide important practice opportunities, but these methods are not sufficient to ensure acquisition of communication and counseling skills. More qualitative studies are needed to understand the nuances of if and how students might acquire such skills via simulated learning experiences. We offer some suggestions for improvement of future studies on this topic. [ABSTRACT FROM AUTHOR]

Purpose: Forward masking (FM) is characterized by the perception of a signal being reduced or wholly masked due to a preceding sound (masker) of the same or different frequencies that offers a challenge for the auditory system to resolve. Considering that the off-frequency masker is expected to undergo linear processing compared to the on-frequency masker at the signal place, it reflects the peripheral auditory systems' compressive response. Thus, the present study focused on employing FM electrophysiological analogous such as auditory brainstem responses (ABR) to the behavioral masking experiments to objectively measure the frequency and level of processing in the auditory system, from the periphery to the brainstem level. Method: The study was an observational research on 21 female volunteers. ABR was obtained using a tone-on-tone FM paradigm for 1000- and 4000-Hz probe stimuli. An experiment used two forward maskers, on-frequency and off-frequency, with varying levels from 50 to 70 dB SPL. Results: A progressive shift for Vth peak latency and reduction in response amplitude was observed in proportion to the increase of masker level for both the probe stimuli and the masking experiments. However, ABR responses in neither masking condition were observed to differ between 60 and 70 dB SPL. Conclusion: FM ABR experiments are an assessment tool for estimating frequency and level processing in the auditory system, providing good efficiency, reliability, and less subject bias compared to behavioral measures. [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]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. The objectives of this study were to determine if weaning would induce behavioral and physiological indicators of a negative affective state, and if supplementation of inactivated Lactobacillus helveticus (ILH) to dairy calves would reduce those indicators of negative affect during weaning. Male Holstein calves (n = 23) were enrolled in the study on d 1 of life. The calves were housed in individual pens in 1 of 4 rooms for the 42-d study. Calves began a step-down weaning from 9 L/d of milk replacer (MR), at 150 g of MR powder/L, on d 35 and received 6 L/d on d 35 to 36, 3 L/d on d 37 to 38, and 0.4 L/d on d 39 to 42. The MR was divided between 3 meals/d until the last 0.4 L/d phase, which was divided between 2 meals/d. Calves had ad libitum water access throughout the study and calf starter from d 28 onward. Within room, calves were assigned to 1 of 2 treatments: (1) control (CON; n = 11) and (2) 5 g of ILH/d split over and mixed into the 0800 h and 2000 h milk feedings from d 3 to 42 (ILH; n = 12). Lying behavior was recorded using HOBO data loggers from d 21 to 41. On d 33, 37, and 41, infrared eye images were taken to determine maximum eye temperature (MET), saliva samples were collected to determine cortisol concentration, and play assessments were conducted to quantify play behavior. On d 34, 38, and 42, blood samples were collected to determine blood serotonin concentration, whereas on d 38 and 39, calves were tested with a cognitive task. A subset of calves (n = 5/treatment) were euthanized to collect gut and brain tissue samples for serotonin concentration on d 43. Weaning resulted in fewer (d 37–41; tendency: d 36), but longer (d 38–41; tendency: d 37), lying bouts and reduced play (d 41), although no changes in lying time, MET, saliva cortisol, nor blood serotonin were detected with initiation of weaning. Supplementation of ILH was associated with less lying time throughout the study, and reduced play duration and higher salivary cortisol during weaning. No differences in lying bouts, play count, blood and tissue (colon, ileum, prefrontal cortex and brain stem) serotonin concentration, and time to complete the cognitive task were detected between the treatments. Overall, weaning induced behavioral changes indicative of negative affective state, and some behavioral differences were observed with ILH supplementation both before and during weaning, with some physiological changes observed during weaning. [ABSTRACT FROM AUTHOR]

This article proposes a framework for understanding the macro-scale organization of anatomical pathways in the mammalian brain. The architecture supports flexible behavioral decisions across a spectrum of spatiotemporal scales. The proposal emphasizes the combinatorial, reciprocal, and reentrant connectivity—called CRR neuroarchitecture—between cortical, BG, thalamic, amygdala, hypothalamic, and brainstem circuits. Thalamic nuclei, especially midline/intralaminar nuclei, are proposed to act as hubs routing the flow of signals between noncortical areas and pFC. The hypothalamus also participates in multiregion circuits via its connections with cortex and thalamus. At slower timescales, long-range behaviors integrate signals across levels of the neuroaxis. At fast timescales, parallel engagement of pathways allows urgent behaviors while retaining flexibility. Overall, the proposed architecture enables context-dependent, adaptive behaviors spanning proximate to distant spatiotemporal scales. The framework promotes an integrative perspective and a distributed, heterarchical view of brain function. [ABSTRACT FROM AUTHOR]

Our body temperature is normally kept within a narrow range of 1°C. For example, if our body temperature rises, such as in a hot environment or due to strenuous exercise, our thermoregulatory system will trigger a powerful heat defense response with vasodilation, sweating, and lowered metabolism. During fever, which often involves body temperatures of up to 41°C, this heat defense mechanism is apparently inhibited; otherwise, the rising body temperature would be immediately combated, and fever would not be allowed to develop. New evidence suggests how and where this inhibition takes place. In two consecutive studies from Cheng et al. and Xu et al., it has been shown that prostaglandin E2, which generates fever by acting on thermosensory neurons in the preoptic hypothalamus, also acts on neurons in the brainstem parabrachial nucleus, which receive temperature information from temperature-activated spinal cord neurons and relay this information to the thermoregulatory center in the hypothalamus to either induce cold or heat defenses. By acting on the same type of prostaglandin E2 receptor that is critical for fever generation in the preoptic hypothalamus, the EP3 receptor, prostaglandin E2 inhibits the signaling of the heat-responsive parabrachial neurons, while stimulating the cold-responsive neurons. These novel findings thus show that prostaglandin E2, by binding to the same receptor subtype in the parabrachial nucleus as in the preoptic hypothalamus, adjusts the sensitivity of the thermosensory system in a coordinated manner to allow the development of febrile body temperatures. [ABSTRACT FROM AUTHOR]

Background: The perivascular spaces of the brain are also known as Virchow-Robin spaces (VRSs). Dilated Virchow-Robin spaces in the brainstem are rare and mainly cause symptoms due to obstructive hydrocephalus, less frequently because of their size, mass effect, and impact on eloquent structures. Case illustration: We present a patient with giant tumefactive VRS with hydrocephalus and neurological symptoms who was treated with endoscopic third ventriculostomy (ETV) followed by microscopic cyst fenestration. On the basis of this observation, we performed a thorough review of the literature to evaluate different treatment options. Results: An 11-year-old girl presented with a headache for 3 months. The patient had a giant tumefactive mesencephalothalamic VRS with triventricular hydrocephalus. She was initially treated with endoscopic third ventriculostomy and multiple cyst fenestration. Symptomatic cyst regrowth required multiple cyst fenestrations via transcallosal transchoroidal (N = 2) and subtemporal approaches (N = 1) at the 2- and 4-year follow-ups. A literature review of these conditions allowed the detection of 12 cases (including our index case), and only 25% (3/12) of the patients underwent cyst fenestration 16.7% (2/12) required endoscopic fenestration and 8.3% (1/12) required microscopic fenestration. Conclusion: Giant mesencephalothalamic dVRSs are rare in the pediatric population. These patients are usually symptomatic due to obstructive hydrocephalus. Surgical options are endoscopic third ventriculostomy, ventricular shunt procedures, or direct cyst fenestration (microscopic or endoscopic). Close follow-up is mandatory owing to the risk of progression of the disease. Cyst fenestration resolves symptoms immediately, as it addresses both hydrocephalus and mass effects due to the cystic lesion in the same setting. [ABSTRACT FROM AUTHOR]

Introduction: Since the initial identification of Miller Fisher syndrome (MFS) and Bickerstaff brainstem encephalitis (BBE),significant milestones have been achieved in understanding these diseases.Discoveries of common serum antibodies (IgG anti-GQ1b), antecedent infections, neurophysiological data, andneuroimaging suggested a shared autoimmune pathogenetic mechanism rather than distinct pathogenesis, leadingto the hypothesis that both diseases are part of a unified syndrome, termed "Fisher-Bickerstaff syndrome". The subsequent identification of atypical anti-GQ1b-positive forms expanded the classification to a broader condition known as "Anti-GQ1b-Antibody syndrome". Methods: An exhaustive literature review was conducted, analyzing a substantial body of research spanning from the initialdescriptions of the syndrome's components to recent developments in diagnostic classification and researchperspectives. Results: Anti-GQ1b syndrome encompasses a continuous spectrum of conditions defined by a common serological profilewith varying degrees of peripheral (PNS) and central nervous system (CNS) involvement. MFS and BBE represent theopposite ends of this spectrum, with MFS primarily affecting the PNS and BBE predominantly involving the CNS.Recently identified atypical forms, such as acute ophthalmoparesis, acute ataxic neuropathy withoutophthalmoparesis, Guillain-Barré syndrome (GBS) with ophthalmoparesis, MFS-GBS and BBE-GBS overlap syndromes,have broadened this spectrum. Conclusion: This work aims to provide an extensive, detailed, and updated overview of all aspects of the anti-GQ1b syndromewith the intention of serving as a stepping stone for further shaping thereof. Special attention was given to therecently identified atypical forms, underscoring their significance in redefining the boundaries of the syndrome. [ABSTRACT FROM AUTHOR]

The article discusses the use of the BRAF inhibitor dabrafenib for the treatment of pilocytic astrocytoma with the BRAF V599ins mutation in an 8-year-old boy. The case report details the patient's symptoms, diagnosis, treatment, and response to dabrafenib therapy, showing significant improvement in neurological deficits and tumor size reduction. The study highlights the effectiveness of molecular targeted therapy over conventional chemotherapy for tumors with rare mutations like BRAF V599ins, emphasizing the importance of thorough molecular testing for appropriate treatment decisions. [Extracted from the article]

This study aimed to investigate whether the RapidPlan (RP) model configured by volumetric modulated arc therapy (VMAT) plans of nasopharyngeal carcinoma (NPC) could be used to assist in the optimization of HT plans and improve their quality. An RP model was trained using 100 clinically accepted VMAT plans of NPC patients. The predicted dose constraints of the VMAT trained RP model were used to reoptimize 25 consecutive clinically accepted HT plans (HT_clinical) and perform new VMAT plans based on the same computed topography (CT). The dosimetric quality of the reoptimized HT plans (HT_reoptimized), HT_clinical, and VMAT group were compared. The minimum dose encompassing 2% target (D 2%), the minimum dose encompassing 98% target (D 98%), homogeneity index (HI) and conformity index (CI) were similar for most targets between the HT_clinical and HT_reoptimized plans, although certain targets in the HT_reoptimized plans had higher D 2% and HI and lower D 98%. The HT_reoptimized plans outperformed the HT_clinical plans in the Dmax and D1cc of the spinal cord, V 40Gy of the left temporal lobe, Dmean and V 30Gy of the oral cavity, Dmean of the larynx and thyroid, and the differences were statistically significant. HT plans had higher CI and HI than VMAT plans. HT plans outperformed VMAT plans in the Dmax of the spinal cord and lenses, V 30Gy of the oral cavity and parotids, and V 40Gy of the temporal lobes, but underperformed in the Dmax and D1cc of the brainstem, D1cc of the spinal cord and Dmean of the oral cavity. The VMAT-based RP model can be used to assist in the planning of HT plans and improve the dosimetry quality of HT plans. [ABSTRACT FROM AUTHOR]

Potassium nitrate (KNO 3) suppresses nociception induced by dental hypersensitivity (HYS). We aimed to examine the effects of KNO 3 on the neural activity of the trigeminal spinal subnucleus caudalis (Vc) in HYS model rats. KNO 3 or vehicle was applied to the exposed dentin of HYS rats for 3 days. c-Fos expression and neuronal activity in the Vc after acetone treatment for cold stimulation were examined to evaluate the effects of KNO 3 application on dentin. The number of c-Fos-immunoreactive cells in the Vc was lower in the group that received KNO 3 (KNO 3 group) than in the group that received vehicle (control group). Spike firing of Vc neurons in response to cold stimulation of the dentin was recorded before and after KNO 3 application to the cavity, and the increased neural activity was effectively suppressed by KNO 3 application. Scanning electron microscopy revealed that the dentin tubules were not occluded by deposits in any of the groups. KNO 3 -induced suppression of Vc neuronal activity does not involve physical occlusion of the dentin tubules but likely involves suppression of Aδ or C-fiber activities in the tooth pulp, resulting in the suppression of Vc neuronal activities. [ABSTRACT FROM AUTHOR]

Introduction: Intracranial schwannomas represent a rare group of intracranial tumors, with purely motor nerve schwannomas being the rarest of them. The anatomical proximity of these tumors to the brainstem may present a radiological challenge in differentiating them from intra–axial brainstem tumors, which can influence further decision–making and treatment options. Methods: We report on a 47–year–old male patient who was diagnosed with a large cystic intracranial tumor with radiological features suggestive of an intrinsic brainstem glioma. Results: After discussing treatment options and risks based on a presumed radiological diagnosis, microsurgical treatment via lateral–suboccipital craniotomy in semi–sitting position, under continuous intraoperative neuromonitoring was performed. Intraoperative findings proved that the tumor was an extra–axial schwannoma originating from the left trochlear nerve. Gross total removal of the lesion was achieved. Conclusion: Due to their rarity, non–specific symptoms and the possibility to mimicking intra–axial brainstem tumors on imaging, these tumors may present a diagnostic challenge and should be taken into account during treatment decision-making. [ABSTRACT FROM AUTHOR]

Background: Post-traumatic headache (PTH) is a common comorbid symptom affecting at least one-third of patients with mild traumatic brain injury (mTBI). While neuroinflammation is known to contribute to the development of PTH, the cellular mechanisms in the trigeminal system crucial for understanding the pathogenesis of PTH remain unclear. Methods: A non-invasive repetitive mTBI (4 times with a 24-h interval) was induced in male mice and effect of mTBI was tested on either bregma or pre-bregma position on the head. Periorbital allodynia and spontaneous pain behavior were assessed using von Frey test and grimace score, respectively. Quantitative PCR was used to assess extent of mTBI pathology. RNA sequencing was performed to obtain transcriptomic profile of the trigeminal ganglion (TG), trigeminal nucleus caudalis (Sp5C) and periaqueductal gray (PAG) at 7 days post-TBI. Subsequently, quantitative PCR, in situ hybridization and immunohistochemistry were used to examine mRNA and protein expression of glia specific markers and pain associated molecules. Results: The repetitive impacts at the bregma, but not pre-bregma site led to periorbital hypersensitivity, which was correlated with enhanced inflammatory gene expression in multiple brain regions. RNA sequencing revealed mTBI induced distinct transcriptomic profiles in the peripheral TG and central Sp5C and PAG. Using gene set enrichment analysis, positive enrichment of non-neuronal cells in the TG and neuroinflammation in the Sp5C were identified to be essential in the pathogenesis of PTH. In situ assays also revealed that gliosis of satellite glial cells in the TG and astrocytes in the Sp5C were prominent days after injury. Furthermore, immunohistochemical study revealed a close interaction between activated microglia and reactive astrocytes correlating with increased calretinin interneurons in the Sp5C. Conclusions: Transcriptomics analysis indicated that non-neuronal cells in peripheral TG and successive in situ assays revealed that glia in the central Sp5C are crucial in modulating headache-like symptoms. Thus, selective targeting of glia cells can be a therapeutic strategy for PTH attributed to repetitive mTBI. [ABSTRACT FROM AUTHOR]

Background: Headache is a pain disorder present in populations world-wide with a higher incidence in females. Specifically, the incidences of medication overuse headache (MOH) have increased worldwide. Comorbidities of MOH include photosensitivity, anxiety, "brain fog", and decreased physical activity. The FDA-approved long-lasting selective β2-adrenergic receptor agonist, formoterol, is currently approved for use in severe asthma and chronic obstructive pulmonary disease. Recently, interest in repurposing formoterol for use in other disorders including Alzheimer's disease, and neuropathic pain after spinal cord injury and traumatic brain injury has gained traction. Thus, revisiting known side-effects of formoterol, like headache and anxiety, could inform treatment paradigms. The endocannabinoid (eCB) system is implicated in the etiology of preclinical headache, with observed decreases in the circulating levels of endogenous cannabinoids, referred to as Clinical Endocannabinoid Deficiency. As cross-talk between the eCB system and adrenergic receptors has been reported, this study investigated the role of the eCB system and ability of formoterol to induce headache-like periorbital allodynic behavior. Methods: Female 8-week-old C57Bl/6J mice were treated daily with formoterol (0.3 mg/kg, i.p.) for up to 42-days, during which they were assessed for periorbital allodynia, open field/novel object recognition, and photosensitivity. At the end of the study, the periaqueductal grey (PAG), a brain region known to contribute to both headache induction and maintenance, was collected and subjected to LC-MS to quantify endocannabinoid levels. Results: Mice exhibited periorbital allodynia at nearly all time points tested and photosensitivity from 28-days onward. Levels of endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), along with cannabinoid receptor 1 (CB1R) expression were altered by both age and upon treatment with formoterol. Administration of FAAH/MAGL inhibitors, to target the eCB system, and a non-selective cannabinoid receptor agonist, WIN 55,212 reversed the formoterol-induced periorbital allodynia. Conclusions: These results suggest that formoterol is dysregulates eCB tone to drive headache-like periorbital allodynic behaviors. These results could help inform preventative treatment options for individuals receiving formoterol, as well as provide information on the interaction between the eCB and adrenergic system. [ABSTRACT FROM AUTHOR]

Background: Although most pilocytic astrocytomas grow slowly, their progression in critical sites such as the brainstem or hypothalamus may prove fatal much more rapidly. Cystic progression may be more problematic than solid tumor. Patients with progressive cystic PAs located in eloquent deep areas of the brain are the best candidates for stereotactic radiosurgery. Objective: This retrospective case series aims to present the effective outcomes obtained from GKRS, targeting the mural nodules of symptomatic eloquently deep-seated cystic PAs in 9 consecutive patients treated at the IMC Gamma Knife Centre in Cairo, Egypt, between 2003 and 2021. Patient and methods: The median follow-up period was 84 months (range 24–240 months). The median treated mural nodule volume was 1.25 cm3 (range 0.32–1.97 cm3), treated with a median peripheral prescription dose of 12 Gy and a median maximum dose of 24 Gy. The median cyst volume in treated patients was 7.64cm3(range 1.66–40.6cm3). Results: At the last follow-up, 7 out of 9 patients (78%) achieved tumor control (marked reduction > 50% of the entire tumor volume in 6 patients and moderate tumor reduction < 50% in one patient) in addition to clinical improvement. The median time of confirmed tumor reduction was 18 months (range 12–32 months). Two patients reported progression of the treated tumor. The overall tumor control rates at 2, 5, and 7 years of follow-up were 88.9%, 78%, and 78%, respectively. Conclusion: The encouraging results of this series indicate that limiting the GKRS to the mural nodule of eloquently deep-seated cystic PAs may be a practical and effective pattern in the salvage of its treatment. Our data do not support radiation for extensive, large symptomatic cysts in deep-seated cystic PA or patients where microsurgical removal is feasible. [ABSTRACT FROM AUTHOR]

Background: Cochlea implants (CIs) show great variability in their outcomes in term of speech perception. Auditory evoked potentials (AEPs) have emerged as valuable procedure in the evaluation of cochlear implants (CIs). AEPs provide an objective and non-invasive assessment of auditory function along the whole auditory pathway from the cochlea to the auditory cortex, enables insights into auditory processing capabilities and the transmission of auditory signals. This article provides a revision of different types of AEPs that can be used for evaluating CIs AEPs regarding their origin, procedure, and their clinical implications. It also explores their potentials role in the assessment and evaluating the efficacy of CIs, highlighting their advantages over traditional behavioral measures, disadvantages and limitations. Conclusion: Overall, AEPs play a critical role in evaluating CIs, offering objective assessment, individualized programming, early issue detection, and research possibilities, thereby enhancing the outcomes and advancements in cochlear implant technology. [ABSTRACT FROM AUTHOR]

Background: This study aims to evaluate the effectiveness of recording cochlear microphonics (CM) using auditory brainstem response (ABR) protocols by comparing them with those obtained using electrocochleography (ECochG) protocols. To achieve this objective, 30 healthy participants aged 15–25 years were recruited. CM recordings were recorded using both ABR and ECochG protocols, utilizing three different stimuli (500-Hz tone burst (10 ms & 18 ms) and a 0.1-ms click), each presented at 100-dB SPL through insert earphones. In the ABR protocol, the non-inverting electrode was placed on the mastoid of the test ear, while in the ECochG protocol, a TipTrode was inserted inside the ear canal. The inverting electrode was placed on the mastoid of the non-test ear, and the ground electrode was positioned on the upper forehead for both protocols. The amplitude and onset latency of the recorded CM were then analyzed. Results: The study found that CM was detectable in 100% of subjects in both ABR and ECochG protocols when 500-Hz tone bursts were utilized. However, CM was recorded in 86.7% of ears using click stimuli in the ECochG protocol and in 80% of ears using the ABR protocol. The CM amplitude recorded with the ECochG protocol was significantly higher than that recorded with the ABR protocol. Additionally, CM amplitude elicited by tone bursts was significantly higher than that evoked by click stimuli in both protocols. The onset latency of CM evoked by click stimuli showed no significant differences between both protocols. However, the onset latency of CM evoked by 500-Hz tone bursts recorded via the ECochG protocol was significantly earlier compared to that recorded via the ABR protocol. Conclusion: The findings of the study suggest that the CM could be recorded using the scalp electrode with ABR protocol also, and this could lead to a cost- and time-effective procedure where audiologists can simultaneously record both cochlear potentials and neural responses. Findings also demonstrate that these recordings could be optimized and more reliably detected across subjects using 500-Hz tone bursts. These insights can guide clinical and research applications in auditory diagnostics and assessments. [ABSTRACT FROM AUTHOR]

The arousal systems of the brainstem, specifically the locus coeruleus-noradrenaline system, respond "phasically" during decisions. These central arousal transients are accompanied by dilations of the pupil. Mechanistic attempts to understand the impact of phasic arousal on cognition would benefit from temporally precise experimental manipulations. Here, we evaluated a non-invasive candidate approach to manipulate arousal in humans: presenting task-irrelevant auditory stimuli at different latencies during the execution of a challenging task. Task-irrelevant auditory stimuli drive responses of brainstem nuclei involved in the control of pupil size, but it is unknown whether such sound-evoked responses mimic the central arousal transients evoked during cognitive computations. A large body of evidence has implicated central arousal transients in reducing bias during challenging perceptual decisions. We thus used challenging visual decisions as a testbed, combining them with task-irrelevant sounds of varying onset latency or duration. Across three experiments, the sounds consistently elicited well-controlled pupil responses that superimposed onto task-evoked responses. While we replicated a negative correlation between task-evoked pupil responses and bias, the task-irrelevant sounds had no behavioral effect. This dissociation suggests that cognitive task engagement and task-irrelevant sounds may recruit distinct neural systems contributing to the control of pupil size. [ABSTRACT FROM AUTHOR]

The sensation of gravity anchors our perception of the environment and is important for navigation. However, the neural circuits that transform gravity into commands for navigation are undefined. We first determined that larval zebrafish (Danio rerio) navigate vertically by maintaining a consistent heading across a series of upward climb or downward dive bouts. Gravity-blind mutant fish swim with more variable heading and excessive veering, leading to less effective vertical navigation. After targeted photoablation of ascending vestibular neurons and spinal projecting midbrain neurons, but not vestibulospinal neurons, vertical navigation was impaired. These data define a sensorimotor circuit that uses evolutionarily conserved brainstem architecture to transform gravitational signals into persistent heading for vertical navigation. The work lays a foundation to understand how vestibular inputs allow animals to move effectively through their environment. What are the neural circuits that transform gravity signals into neuronal signals for navigation? This study describes a sensorimotor circuit that transforms gravitational signals into persistent heading for vertical navigation, showing how vestibular inputs allow animals to move effectively through their environment. [ABSTRACT FROM AUTHOR]

Background: Cochlear synaptopathy is a disorder where auditory perceptual impairments, such as speech perception in noise and tinnitus, may not be accurately reflected by audiometric thresholds, even if the audiogram appears normal. It is proposed that the connections between hair cells and the auditory nerve are more susceptible to sound and aging damage than the cochlea's hair cells. Cochlear synaptopathy can be present in ears with normal audiograms and undamaged hair cells, leading to hidden hearing loss. This study aims to construct electrophysiological and behavioral auditory parameters associated with persons exposed to loudness and having normal audiograms and auditory complaints to identify hidden hearing loss. Results: A case–control study was done with forty participants with a documented history of exposure to loud sounds and various auditory complaints, compared to a control group of forty persons who had all been confirmed to have normal audiograms. The chosen behavioral core tests comprised the speech intelligibility in noise test (SPIN), gaps detection in noise (GIN test), and pitch pattern sequence test (PPS). The electrophysiological measures utilized in the study were the auditory brainstem response test (ABR) and electrocochleography (ECochG). The SPIN, PPS, and GIN test results demonstrated statistically significant disparities between the control and case groups. The amplitude ratio of wave I to wave V in ABR and the ratio of EcochG AP to SP demonstrated a statistically significant variance between the two groups. The SPIN test exhibited the highest AUC, signifying its superior diagnostic capability in identifying hidden hearing loss. Conclusion: The present study has shown that the SPIN, as a behavioral test, and the EcochG AP amplitude measure, as an electrophysiological test, provide the greatest auditory diagnostic capability for identifying cochlear synaptopathy. Wave I amplitude in the auditory brainstem response (ABR) and the SP/AP ratio in electrocochleography (EcochG) are promising non-behavioral measures of cochlear synaptopathy or hidden hearing loss. [ABSTRACT FROM AUTHOR]

Introduction: Speech sound disorder (SSD) is a speech and language disorder associated with difficulties in motor production, perception, and phonological representation of sounds and speech segments. Since auditory perception has a fundamental role in forming and organizing sound representation for its recognition, studies that evaluate the cortical processing of sounds are required. Thus, the present study aimed to verify the relation between SSD severity measured by the percentage of correct consonants (PCCs) with the cortical auditory evoked potentials (CAEPs) using speech stimulus. Methods: Twenty-nine children with normal hearing participated in this research and were grouped into three groups by SSD level measured by the PCC index. In addition, the groups were subdivided according to the children's age group: between 60–71 months, 72–83 months, and 83–94 months. The CAEP with speech stimulus was carried out in all children. Results: Older children had longer P1 and N1 latencies. In P2 latency, there was an interference of age only in the severe group. The N2 latency was affected by age, where older children had longer latency. Conclusion: The amplitude of CAEP has not suffered any interference with the age, or severity of SSD. For the latency, older children generally presented longer averages than younger ones. Plain Language Summary: Speech sound disorders (SSDs) are a language disorder prevalent in children and are featured by difficulties in the perception, production, and organization of speech sounds. This disorder can be associated with some deficits in the sound process. Thus, this study used a speech stimulus to measure the relationship between age and SSD severity, measured by the percentage of correct consonants, with cortical auditory evoked potentials (CAEPs). The latency of P1, N1, P2, N2, and P3 components and P1-N1, P2-N2, and P3 amplitudes were analyzed in both ears. No interference of severity, age, and ear was found in the latency of P1 and N1 components. The P2 latency was longer than the one proposed in the literature, and younger children with more severe SSD had lower mean latency values for this component. No interaction was found between the N2 latency and SSD severity. As for P3 latency, all children in this study had values within the normal limits for the age group. No SSD severity, age, and ear interference were observed in the P1-N1 amplitude. However, it was observed that the amplitude of this complex increases with age and decreases with SSD severity in the right ear. Finally, there was no SSD severity, age, and ear interference in P2-N2 and P3 amplitudes. CAEP analysis showed important aspects of the auditory path of children with SSD, suggesting difficulty in directing attention and discriminating the stimuli used, which can interfere with the phonological representation of speech sounds. [ABSTRACT FROM AUTHOR]

Background: The delivery of drugs into the inner ear is a challenging field of study due to the complex cochlear anatomy and physiology. The creation of an intracochlear device that allows for short- and long-term intracochlear delivery of the drugs with a minimal invasive technology is needed to prevent or treat conditions that can potentially prevent the development of permanent hearing loss. Aim: This study intends to test the efficacy of DXM-infused PLGA microneedles created in our laboratory in an in vivo animal model of acute ototoxic injury. Material and Methods: Twenty-four male Norway Brown rats were randomized into four groups, three of which groups received an intratympanic injection of ethacrynic acid and kanamycin. Two of these groups underwent the placement of an intracochlear microneedle blended or not with dexamethasone, and two groups underwent implantation of a plain microneedle, one of without prior exposure to the ototoxic agent to confirm in vivo biocompatibility. Animals were then followed with a weekly auditory brainstem response testing until day 28 after surgical intervention. Result and Conclusion: Our intracochlear device demonstrated biocompatibility and produced no hearing changes after its implantation in the control group. Inserted DXM-blended microneedles prevented hearing deterioration in those animals exposed to an ototoxic environment. [ABSTRACT FROM AUTHOR]

The physiological diversity of inhibitory neurons provides ample opportunity to influence a wide range of computational roles through their varied activity patterns, especially via feedback loops. In the avian auditory brain stem, inhibition originates primarily from the superior olivary nucleus (SON), and so it is critical to understand the intrinsic physiological properties and processing capabilities of these neurons. Neurons in the SON receive ascending input via the cochlear nuclei: directly from the intensity-coding cochlear nucleus angularis (NA) and indirectly via the interaural timing nucleus laminaris (NL), which itself receives input from cochlear nucleus magnocellularis (NM). Two distinct populations of SON neurons provide inhibitory feedback either to ipsilateral NA, NL, and the timing cochlear nucleus NM or to the contralateral SON. To determine whether these populations correspond to distinct response types, we investigated their electrophysiology in brain stem slices, using patch-clamp electrophysiology. We identified three phenotypes: single-spiking, chattering tonic, and regular tonic neurons. The two tonic phenotypes displayed distinct firing patterns and different membrane properties. Fluctuating "noisy" currents used to probe the capability of SON neurons to encode temporal features showed that each phenotype differed in sensitivity to temporally modulated input. By using cell fills and anatomical reconstructions, we could correlate the firing phenotypes with their axonal projection patterns. We found that SON axons exited via three fiber tracts, with each tract composed of specific phenotypes. These results provide a basis for understanding the role of specific inhibitory cell types in auditory function and elucidate the organization of the SON outputs. NEW & NOTEWORTHY: Inhibitory inputs for the avian brain stem originate primarily from the superior olivary nucleus (SON). We describe three intrinsic phenotypes of SON neurons and show how they differ in their temporal processing and projection patterns. We propose that the two types of tonic firing neurons (including one novel type) and the single-spiking neurons in SON comprise separate feedback circuits that may differentially influence the auditory information flowing via the cochlear nuclei and nucleus laminaris. [ABSTRACT FROM AUTHOR]

The rhomboid fossa (RF) is a crucial anatomical region in brainstem surgery as it contains essential structures such as the reticular formation and cranial nerve nuclei. This study aimed to provide a detailed understanding of the complex microsurgical anatomy of the RF, which is vital for the safe execution of neurosurgical procedures. Morphometric analysis was conducted on 45 adult human brainstems preserved in 10% formalin. Under 20× magnification, 13 linear measurements were performed using a millimeter graph to identify key anatomical landmarks. The RF measured 34.65 mm in length and 22.61 mm in width. The facial colliculus measured 4.26 mm in length on the left and 4.45 mm on the right, with corresponding widths of 3.77 mm and 3.50 mm. The distance between the sulcus limitans incisures was 9.52 mm, and the distance from the upper border of the medullary striae to obex was 11.53 mm. The proximity of the facial colliculus to the median sulcus was measured at 0.86 mm on the right and 0.96 mm on the left. Additionally, 2 safe entry zones—the suprafacial and infrafacial triangles—were identified, offering pathways to reach dorsal pons lesions through the RF. This comprehensive morphometric analysis of the RF enhances the understanding of its intricate anatomy. By describing safe entry zones, the suprafacial and infrafacial triangles, and providing precise measurements of key anatomical features, this study serves as a valuable resource for neurosurgeons in planning and executing brainstem surgeries. [ABSTRACT FROM AUTHOR]

Neuronal activity requires a large amount of ATP, leading to a rapid collapse of brain function when aerobic respiration fails. Here, we summarize how rhythmic motor circuits in the brain stem of adult frogs, which normally have high metabolic demands, transform to produce proper output during severe hypoxia associated with emergence from hibernation. We suggest that general principles underlying plasticity in brain bioenergetics may be uncovered by studying nonmammalian models that face extreme environments, yielding new insights to combat neurological disorders involving dysfunctional energy metabolism. [ABSTRACT FROM AUTHOR]

The clinical manifestation of Parkinson's disease exhibits significant heterogeneity in the prevalence of non-motor symptoms and the rate of progression of motor symptoms, suggesting that Parkinson's disease can be classified into distinct subtypes. In this study, we aimed to explore this heterogeneity by identifying a set of subtypes with distinct patterns of spatiotemporal trajectories of neurodegeneration. We applied Subtype and Stage Inference (SuStaIn), an unsupervised machine learning algorithm that combined disease progression modelling with clustering methods, to cortical and subcortical neurodegeneration visible on 3 T structural MRI of a large cross-sectional sample of 504 patients and 279 healthy controls. Serial longitudinal data were available for a subset of 178 patients at the 2-year follow-up and for 140 patients at the 4-year follow-up. In a subset of 210 patients, concomitant Alzheimer's disease pathology was assessed by evaluating amyloid-β concentrations in the CSF or via the amyloid-specific radiotracer 18F-flutemetamol with PET. The SuStaIn analysis revealed three distinct subtypes, each characterized by unique patterns of spatiotemporal evolution of brain atrophy: neocortical, limbic and brainstem. In the neocortical subtype, a reduction in brain volume occurred in the frontal and parietal cortices in the earliest disease stage and progressed across the entire neocortex during the early stage, although with relative sparing of the striatum, pallidum, accumbens area and brainstem. The limbic subtype represented comparative regional vulnerability, which was characterized by early volume loss in the amygdala, accumbens area, striatum and temporal cortex, subsequently spreading to the parietal and frontal cortices across disease stage. The brainstem subtype showed gradual rostral progression from the brainstem extending to the amygdala and hippocampus, followed by the temporal and other cortices. Longitudinal MRI data confirmed that 77.8% of participants at the 2-year follow-up and 84.0% at the 4-year follow-up were assigned to subtypes consistent with estimates from the cross-sectional data. This three-subtype model aligned with empirically proposed subtypes based on age at onset, because the neocortical subtype demonstrated characteristics similar to those found in the old-onset phenotype, including older onset and cognitive decline symptoms (P < 0.05). Moreover, the subtypes correspond to the three categories of the neuropathological consensus criteria for symptomatic patients with Lewy pathology, proposing neocortex-, limbic- and brainstem-predominant patterns as different subgroups of α-synuclein distributions. Among the subtypes, the prevalence of biomarker evidence of amyloid-β pathology was comparable. Upon validation, the subtype model might be applied to individual cases, potentially serving as a biomarker to track disease progression and predict temporal evolution. [ABSTRACT FROM AUTHOR]

Simple Summary: Proton beam radiation therapy is one of the major treatment modalities used for cancer treatment, including brain tumors. This treatment modality is distinct from other radiation options because of its ability to deliver radiation to tumor targets while sparing healthy tissue. Brainstem toxicity is a rare but important complication can arise due to exposure to radiation; hence, in this systematic review and meta-analysis, we aimed to explore the risk of brainstem toxicity in pediatric brain tumor patients undergoing proton beam radiation, focusing on quantifying its incidence and severity. Eleven articles were considered eligible in our study, and the results yielded an overall brainstem toxicity incidence of 1.8%, ranging in severity, with Grade 1 brainstem toxicity (asymptomatic) being the most common. This study revealed a low incidence of symptomatic brainstem toxicity and related mortality among pediatric brain tumor patients undergoing proton beam radiation, which could support the idea of it having a good toxicity profile and possibly re-enforces the need for more comprehensive primary studies regarding this radiation modality in brain tumor patients to uncover unknowns and help us understand the grey areas of this topic. Background: Proton beam radiation therapy (PBRT) is an advanced cancer treatment modality that utilizes the distinctive physical properties of protons to precisely deliver radiation to tumor targets while sparing healthy tissue. This cannot be obtained with photon radiation. In this systematic review and meta-analysis, we aimed to comprehensively assess the risk of brainstem toxicity in pediatric brain tumor patients undergoing PBRT. Methods: With adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a predetermined search strategy was used to identify eligible articles from PubMed, Web of Science, Scopus, and Cochrane Library through July 2024. Results: The current study included a total of 11 eligible articles. The pooled prevalence of patients who suffered from brainstem toxicity was 1.8% (95% CI: 1%, 2.6%). The pooled prevalences of patients with Grade 1 to Grade 5 brainstem toxicity were found to be 10.6% (95% CI: 8.8%, 30%), 1.5% (95% CI: 0.6%, 2.5%), 0.7% (95% CI: 0.3%, 1.1%), 0.4% (95% CI: 0.1%, 0.7%), and 0.4% (95% CI: 0.1%, 0.8%), respectively, with an overall pooled prevalence of 0.7% (95% CI: 0.4%, 1%). Conclusions: This study revealed a relatively low incidence of symptomatic brainstem toxicity and its related mortality in the pediatric population undergoing PBRT. However, further research is encouraged to study the broader effects of PBRT and to explore various factors that may influence the risk of brainstem toxicity in patients treated with PBRT. [ABSTRACT FROM AUTHOR]

The article describes the case of a 33-year-old obese female with intermediate-grade melanocytic neoplasma of the cerebellopontine angle (CPA) who underwent subtotal resection and adjuvant radiation therapy. The patient was diagnosed with intermediate-grade primary melanocytic neoplasm. A discussion on tumors of the CPA is offered.

Sub-Tenon's block has a superior safety profile and life-threatening complications such as cardiovascular collapse and brainstem anaesthesia are extremely rare. We report a case of cardiorespiratory collapse following bilateral sub-Tenon's blocks at the conclusion of a laser photocoagulation procedure under general anaesthesia. The cause was most likely brainstem anaesthesia. We explore and discuss the likely mechanisms and other potential differential diagnoses. It highlights the importance of maintaining vigilance following an eye block. Attention should not falter upon completing a block or at the conclusion of a case, regardless of its type or safety profile. This case also illustrates how the presence of general anaesthesia may obscure and delay the diagnosis of brainstem anaesthesia. [ABSTRACT FROM AUTHOR]

Background: Patients may undergo anatomical changes during radiotherapy, leading to an underdosing of the target or overdosing of the organs at risk (OARs). Purpose: 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. Methods: 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. Results: 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. Conclusion: 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]

Both the transfrontal and the suboccipital-transcerebellar approach are frequently used trajectories for frame-based stereotactic biopsies of brainstem lesions. Nevertheless, it remains unclear which approach is more favorable in terms of complications, diagnostic success and outcome, especially considering the location of the lesion within the brainstem. This study compared the safety and diagnostic yield of these two approaches. Furthermore, a brainstem zone model was created to answer the question, whether there is a favorable approach depending on the location of the lesion in the brainstem. A retrospective analysis of 84 consecutive cases of frame-based stereotactic biopsies for brainstem lesions via either transfrontal or suboccipital-transcerebellar approaches over a 16-year period was performed. Clinical and surgical data regarding trajectories, histopathology, complications and outcome was collected. The brainstem was divided in anatomical zones to compare the use of the two approaches depending on the location of the lesions. A total of n = 84 cases of stereotactic biopsies for brainstem lesions were performed. In 36 cases the suboccipital-transcerebellar approach was used, while in 48 cases surgery was performed via the transfrontal approach. The patient's demographic data were comparable between the two approaches. Overall diagnostic yield was 90.5% (93.8% transfrontal vs. 86.1% suboccipital, p = 0.21, Risk Difference (RD) 0.077, CI [-0.0550, 0.2090]). Complications occurred in 11 cases (total complication rate: 13.1%; 12.5% transfrontal vs. 13.9% suboccipital, p = 0.55, RD 0.014, CI [-0.1607, 0.1327]). The brainstem model showed a more frequent use of the suboccipital approach in lesions of the dorsal pons. The transfrontal approach was used more frequently in mesencephalic targets. No significant differences in terms of complications and diagnostic yield were observed, even though complications in medullary lesions appeared higher using the transfrontal approach. This study showed, that if the approaches are used for their intended target locations there are no significant differences between the transfrontal and the suboccipital-transcerebellar approach for frame-based stereotactic biopsies of brainstem lesions in terms of diagnostic yield and safety. Therefore, our data suggests that both approaches should be considered for stereotactic biopsy of brainstem lesions. [ABSTRACT FROM AUTHOR]

Objective: In the past, brain stem was treated with surgery or placement of shunt in Pakistan. Gamma Knife surgery is currently an alternative to surgery for deep brain lesions. In the current study, we show the clinical experience of our Centre treated with Gamma Knife surgery Methods: This is a descriptive study conducted between February 2016 and October 2021. We had total 47 patients presented with focal brainstem gliomas which were selected for Gamma knife radiosurgery at the Neurospinal and Cancer Care Institute Karachi. Results: Clinical Response was observed among them 20 (42.55%) patients improved, 22(46.80%) were stable, while 05 (10.63%) got worse The mean duration of symptoms was 31.9(SD10.5± 3months). Karnofsky Performance Status (KPS) scores during Gamma knife radiosurgery were 90 in 24 patients (51%), 80 in 21 patients (44.6%), and 70 in two patients (4.2%). Four patients (10.6%) had received conventional radiotherapy before Gamma knife radiosurgery. Conclusion: Among the diverse gliomas, their peril varies not just by type but also by their intricate location within the brain. The efficacy of gamma knife radiation is excellent particularly when tackling high-grade tumors, exhibiting its prowess in both adult and pediatric cases. [ABSTRACT FROM AUTHOR]

Introduction: HyperArc (HA) auto‐planning offers simplicity for the end user and consistently high‐quality SRS plans. The "Ask For It" (AFI) optimization strategy offers a manual planning technique that, when coupled with R50%Analytic, can be guided to deliver a plan with an intermediate dose spill "as low as reasonably achievable" and high target dose conformity. A direct comparison of SRS plan quality obtained using the manual planning AFI strategy and HA has been performed. Methods: Using a CT data set available from the Radiosurgery Society, 54 PTVs were created and used to generate 19 individual SRS/SRT cases. Case complexity ranged from single PTV plans to multiple PTV plans with a single isocenter. PTV locations ranged from relative isolation from critical structures to lesions within 1.5 mm of the optic apparatus and abutting the brainstem. All cases were planned using both the AFI and HA optimization strategies as implemented in the Varian Medical Systems Eclipse Treatment Planning System. A range of treatment plan quality metrics were obtained including Intermediate Dose Spill (R50%), Conformity Indices CIRTOG and CIPaddick, PTV Dose Coverage (Dn%), PTV Mean Dose, and Modulation Factor. The Wilcoxon Signed Rank Sum non‐parametric statistical method was utilized to compare the obtained plan quality metrics. Results: Statistically significant improvements were found for the AFI strategy for metrics R50%, CIRTOG, CIPaddick, and PTV Mean Dose (p < 0.001). HA achieved superior coverage for Dn% (p = 0.018), while the Modulation Factors were not significantly different for AFI compared to HA optimization (p = 0.13). Conclusion: This study provides evidence that the AFI manual planning strategy can produce high‐quality planning metrics similar to the HA auto‐planning method. [ABSTRACT FROM AUTHOR]

Deriving human neural responses to natural speech is now possible, but the responses to male- and female-uttered speech have been shown to differ. These talker differences may complicate interpretations or restrict experimental designs geared toward more realistic communication scenarios. This study found that when a male talker and a female talker had the same fundamental frequency, auditory brainstem responses (ABRs) were very similar. Those responses became smaller and later with increasing fundamental frequency, as did click ABRs with increasing stimulus rates. Modeled responses suggested that the speech and click ABR differences were reasonably predicted by peripheral and brainstem processing of stimulus acoustics. [ABSTRACT FROM AUTHOR]

Objective: To investigate changes of myeloid differentiation factor 2 (MD2) in inflammation-induced pain and acupuncture-mediated analgesia. Methods: Mice were randomly divided into three groups by a random number table method: saline group (n=16), complete Freund's adjuvant (CFA) group (n=24) and CFA+electroacupuncture (EA) group (n=26). Inflammation-induced pain was modelled by injecting CFA to the plantar surface of the hind paw of mice and EA was applied to bilateral Zusanli (ST 36) to alleviate pain. Only mice in the CFA+EA group received EA treatment (30 min/d for 2 weeks) 24 h after modelling. Mice in the saline and CFA groups received sham EA. von-Frey test and Hargreaves test were used to assess the pain threshold. Brain and spinal tissues were collected for immunofluorescence staining or Western blotting to quantify changes of MD2 expression. Results: CFA successfully induced plantar pain and EA significantly alleviated pain 3 days after modelling (P<0.01). Compared with the CFA group, the number of MD2+/c-fos+ neurons was significantly increased in the dorsal horn of the spinal cord 7 and 14 days after EA, especially in laminae I – IIo (P<0.01). The proportion of double positive cells to the number of c-fos positive cells and the mean fluorescence intensity of MD2 neurons were also significantly increased in laminae I – IIo (P<0.01). Western blotting showed that the level of MD2 was significantly decreased by EA only in the hippocampus on day 7 and 14 (both P<0.01) and no significant changes were observed in the cortex, thalamus, cerebellum, or the brainstem (P<0.05). Fluorescence staining showed significant decrease in the level of MD2 in periagueductal gray (PAG) and locus coeruleus (LC) after CFA injection on day 7 (P<0.01 for PAG, P<0.05 for LC) and EA significantly reversed this decrease (P<0.01 for PAG, P<0.05 for LC). Conclusion: The unique changes of MD2 suggest that EA may exert the analgesic effect through modulating neuronal activities of the superficial laminae of the spinal cord and certain regions of the brain. [ABSTRACT FROM AUTHOR]

Background: To gain a comprehensive understanding of the altered sensory processing in patients with migraine, in this study, we developed an electroencephalography (EEG) protocol for examining brainstem and cortical responses to sensory stimulation. Furthermore, machine learning techniques were employed to identify neural signatures from evoked brainstem–cortex activation and their interactions, facilitating the identification of the presence and subtype of migraine. Methods: This study analysed 1,000-epoch-averaged somatosensory evoked responses from 342 participants, comprising 113 healthy controls (HCs), 106 patients with chronic migraine (CM), and 123 patients with episodic migraine (EM). Activation amplitude and effective connectivity were obtained using weighted minimum norm estimates with spectral Granger causality analysis. This study used support vector machine algorithms to develop classification models; multimodal data (amplitude, connectivity, and scores of psychometric assessments) were applied to assess the reliability and generalisability of the identification results from the classification models. Results: The findings revealed that patients with migraine exhibited reduced amplitudes for responses in both the brainstem and cortical regions and increased effective connectivity between these regions in the gamma and high-gamma frequency bands. The classification model with characteristic features performed well in distinguishing patients with CM from HCs, achieving an accuracy of 81.8% and an area under the curve (AUC) of 0.86 during training and an accuracy of 76.2% and an AUC of 0.89 during independent testing. Similarly, the model effectively identified patients with EM, with an accuracy of 77.5% and an AUC of 0.84 during training and an accuracy of 87% and an AUC of 0.88 during independent testing. Additionally, the model successfully differentiated patients with CM from patients with EM, with an accuracy of 70.5% and an AUC of 0.73 during training and an accuracy of 72.7% and an AUC of 0.74 during independent testing. Conclusion: Altered brainstem-cortex activation and interaction are characteristic of the abnormal sensory processing in migraine. Combining evoked activity analysis with machine learning offers a reliable and generalisable tool for identifying patients with migraine and for assessing the severity of their condition. Thus, this approach is an effective and rapid diagnostic tool for clinicians. [ABSTRACT FROM AUTHOR]

It remains elusive whether lesions and inflammation in the sub/juxtacortical white matter reflect cortical and/or meningeal pathologies. Elucidating this could have implications for MRI monitoring as sub/juxtacortical lesions are detectable by routine MRI, while cortical lesions and meningeal inflammation are not. By large‐area microscopy, we quantified total and mixed active plaque loads along with densities and sizes of perivascular mononuclear infiltrates (infiltrates) in the sub/juxtacortical white matter ≤2 mm from the cortex, intra‐cortically and in the meninges. Data were related to ante‐mortem clinical parameters in a false discovery rate‐corrected analysis. We compared 12 patients with primary progressive multiple sclerosis (PPMS) and 15 with secondary progressive MS to 22 controls. Fifteen patients and 11 controls contributed with hemispheric sections. Sections were stained with haematoxylin–eosin, for myelin and for microglia/macrophages. B cells and T cells were confirmed in a subset. Immunoglobulin G depositions in selected cortical plaques resembled depositions described before in “slowly expanding” plaques in the white matter. We quantified plaque activity by measuring microglia‐dominated and macrophage‐dominated areas. Sub/juxtacortical plaques (load and activity) reflected plaque activity in the cerebral cortex. Plaque activity and infiltrates were more pronounced in the sub/juxtacortical white matter than in the cerebral cortex while conversely, the total plaque load was highest in the cortex. Infiltrates correlated trans‐cortically and sub/juxtacortical plaque activity reflected cortical and meningeal infiltrates. Sub/juxtacortical infiltrate sizes correlated with shorter survival after progression onset. Two patients with PPMS and putatively fatal brain stem lesions argue against incidental findings. Trans‐cortical inflammatory flares and plaque activity may be pathogenic in progressive MS. We suggest emphasis on sub/juxtacortical MRI lesions as plausible surrogates for cortical and meningeal pathologies and, when present, as indicators for cognitive testing. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by progressively worsening cognitive decline and memory loss. Excessive iron accumulation produces severe cognitive impairment. However, there are no uniform conclusions about changes in brain iron content in AD. This study aimed to investigate the iron content of the deep brain nuclei in AD, and its correlation with cognitive function. Methods: Thirty-one patients with mild to moderate AD, 17 patients with mild cognitive impairment (MCI), and 20 age-, sex-, and education-matched healthy controls (HC) were collected. The QSM was used to quantify the magnetic susceptibility values of the caudate nucleus, putamen, globus pallidus, substantia nigra, red nucleus, and dentate nucleus, and to analyze the differences that existed between the three groups. As well as the correlation between the magnetic susceptibility values and cognitive function was calculated. Results: The magnetic susceptibility values of bilateral globus pallidus, left putamen, and bilateral substantia nigra were significantly higher in AD patients than in HC, and the magnetic susceptibility values of the right globus pallidus were significantly higher in AD patients than in MCI (all p < 0.05). The magnetic susceptibility values of the left dentate nucleus in the AD group were negatively correlated with the writing function of the MMSE subitem (r = -0.42, p = 0.020), and the magnetic susceptibility values of the left caudate nucleus and right dentate nucleus were significantly and negatively correlated with the naming function and language function of the MoCA subitem, respectively (r = -0.43, p = 0.019; r = -0.36, p = 0.048). Conclusion: Magnetic susceptibility values based on QSM correlate with cognitive function are valuable in discriminating AD from MCI and AD from HC. [ABSTRACT FROM AUTHOR]

Anesthesia modifies sensory representations in the thalamo-cortical circuit but is considered to have a milder impact on peripheral sensory processing. Here, tracking the same neurons across wakefulness and isoflurane or ketamine medetomidine anesthesia, we show that the amplitude and sign of single neuron responses to sounds are massively modified by anesthesia in the cochlear nucleus of the brainstem, the first relay of the auditory system. The reorganization of activity is so profound that decoding of sound representation under anesthesia is not possible based on awake activity. However, population-level parameters, such as average tuning strength and population decoding accuracy, are weakly affected by anesthesia, explaining why its effect has previously gone unnoticed when comparing independently sampled neurons. Together, our results indicate that the functional organization of the auditory brainstem largely depends on the network state and is ill-defined under anesthesia. This demonstrates a remarkable sensitivity of an early sensory stage to anesthesia, which is bound to disrupt downstream processing. [ABSTRACT FROM AUTHOR]

Diffuse intrinsic pontine glioma (DIPG) is a highly lethal tumor that occurs in the brain stem. At present, there is no effective drug for DIPG. In this work, Na/K‐ATPase inhibitor‐ouabain (OB) is found to efficiently kill H3K27M‐mutated DIPG at low doses, inhibit tumor cell proliferation, reduce tumor stemness for the first time, demonstrating its potential as a chemotherapy drug for DIPG. In order to increase the blood–brain barrier (BBB) permeability and tumor accumulation of OB, acidic‐responsive engineered exosomes loaded with OB (OB@EXO‐LCCP) are constructed, which increase the accumulation of OB within the tumor microenvironment of DIPG and efficiently deliver OB to DIPG cells to achieve targeted killing effect. In in vitro experiments, OB@EXO‐LCCP is able to release OB in an acid‐responsive manner and effectively kill DIPG tumor cells. In in vivo experiments, OB@EXO‐LCCP significantly inhibits DIPG growth and prolongs the overall survival of DIPG‐bearing mice. Overall, OB@EXO‐LCCP can promote the BBB permeability and tumor‐targeting ability of OB, thereby enhancing its DIPG‐killing ability and reducing its toxicity. This study provides technical and theoretical information for the precision therapy of DIPG. [ABSTRACT FROM AUTHOR]