Ventral Brainstem Research Articles

Revision Chiari surgery in adults: surgical evaluation algorithm and outcomes in a continuity-of-care practice.

Patients with a prior surgical history for Chiari malformation (CM) as a child or an adult who presents with a recurrence or persistence of symptoms pose a challenging clinical scenario. The authors analyzed preoperative presentations, surgical histories, and outcomes of adult CM revision cases to create an algorithm for the assessment of revision surgery in adult CM patients and contrast this with the care of pediatric CM patients within the context of an integrated continuity-of-care CM practice seeing pediatric and adult patients. The authors retrospectively reviewed the records of patients with CM0, -1, and -1.5 who were 21 years of age or older, had a prior history of CM surgery as either children or adults, and underwent revision surgery as adults at the authors' institution from December 2009 to February 2020. The cohort was divided into three groups depending on the type of revision surgery performed: posterior fossa decompression with or without duraplasty (PFD/D group), occipitocervical fusion without ventral decompression (OCF group), and ventral decompression in the form of endoscopic endonasal odontoidectomy (VD group). A total of 50 adult revision cases were divided into 30 PFD/D cases, 13 OCF cases, and 7 VD cases. Forty cases had previously undergone one CM surgery, and 10 had undergone two. Preoperatively, the PFD/D group had significantly fewer cases of diagnosed craniocervical instability (CCI), Ehlers-Danlos syndrome, and dysautonomia than the OCF and VD groups. A retroflexed odontoid was significantly more common in the VD group than in the PFD/D and OCF groups. Postoperatively, rates of improvement were 60.0% with PFD/D, 84.6% with OCF, and 85.7% with VD, but differences in these rates were not statistically significant. In this challenging group of CM patients, possible etiologies warranting additional surgery included residual dorsal compression, persistent syrinx, CCI, and ventral brainstem compression from a significant retroflexed odontoid. Outcomes after revision were often favorable, but careful evaluation, patient selection, and communication with patients are needed in deciding to reoperate. The suggested algorithm can aid decision-making.

Fast Inhibition Slows and Desynchronizes Mouse Auditory Efferent Neuron Activity.

The encoding of acoustic stimuli requires precise neuron timing. Auditory neurons in the cochlear nucleus (CN) and brainstem arewell suited for accurate analysis of fast acoustic signals, given their physiological specializations of fast membrane time constants, fast axonal conduction, and reliable synaptic transmission. The medial olivocochlear (MOC) neurons that provide efferent inhibition of the cochlea reside in the ventral brainstem and participate in these fast neural circuits. However, their modulation of cochlear function occurs over time scales of a slower nature. This suggests the presence of mechanisms that reduce MOC inhibition of cochlear function. To determine how monaural excitatory and inhibitory synaptic inputs integrate to affect the timing of MOC neuron activity, we developed a novel in vitro slice preparation ("wedge-slice"). The wedge-slice maintains the ascending auditory nerve root, the entire CN and projecting axons, while preserving the ability to perform visually guided patch-clamp electrophysiology recordings from genetically identified MOC neurons. The "in vivo-like" timing of the wedge-slice demonstrates that the inhibitory pathway accelerates relative to the excitatory pathway when the ascending circuit is intact, and the CN portion of the inhibitory circuit is precise enough to compensate for reduced precision in later synapses. When combined with machine learning PSC analysis and computational modeling, we demonstrate a larger suppression of MOC neuron activity when the inhibition occurs with in vivo-like timing. This delay of MOC activity may ensure that the MOC system is only engaged by sustained background sounds, preventing a maladaptive hypersuppression of cochlear activity.

Postinspiratory and preBötzinger complexes contribute to respiratory-sympathetic coupling in mice before and after chronic intermittent hypoxia.

The sympathetic nervous system modulates arterial blood pressure. Individuals with obstructive sleep apnea (OSA) experience numerous nightly hypoxic episodes and exhibit elevated sympathetic activity to the cardiovascular system leading to hypertension. This suggests that OSA disrupts normal respiratory-sympathetic coupling. This study investigates the role of the postinspiratory complex (PiCo) and preBötzinger complex (preBötC) in respiratory-sympathetic coupling under control conditions and following exposure to chronic intermittent hypoxia (CIH) for 21 days (5% O2-80 bouts/day). The surface of the ventral brainstem was exposed in urethane (1.5 g/kg) anesthetized, spontaneously breathing adult mice. Cholinergic (ChAT), glutamatergic (Vglut2), and neurons that co-express ChAT and Vglut2 at PiCo, as well as Dbx1 and Vglut2 neurons at preBötC, were optogenetically stimulated while recording activity from the diaphragm (DIA), vagus nerve (cVN), and cervical sympathetic nerve (cSN). Following CIH exposure, baseline cSN activity increased, breathing frequency increased, and expiratory time decreased. In control mice, stimulating PiCo specific cholinergic-glutamatergic neurons caused a sympathetic burst during all phases of the respiratory cycle, whereas optogenetic activation of cholinergic-glutamatergic PiCo neurons in CIH mice increased sympathetic activity only during postinspiration and late expiration. Stimulation of glutamatergic PiCo neurons increased cSN activity during the postinspiratory phase in control and CIH mice. Optogenetic stimulation of ChAT containing neurons in the PiCo area did not affect sympathetic activity under control or CIH conditions. Stimulating Dbx1 or Vglut2 neurons in preBötC evoked an inspiration and a concomitant cSN burst under control and CIH conditions. Taken together, these results suggest that PiCo and preBötC contribute to respiratory-sympathetic coupling, which is altered by CIH, and may contribute to the hypertension observed in patients with OSA.

The progestinic drug, etonogestrel, rescues breathing in a rodent model of central chemoreflex impairment

The central CO2-chemoreflex is crucial in regulating breathing, providing stimulation at rest and during challenges to homeostasis. The retrotrapezoid nucleus (RTN), located in the ventral brainstem, is essential to this process. Impaired RTN function is linked to hypoventilation syndromes, including congenital central hypoventilation syndrome (CCHS) characterized by apnea and blunted responsiveness to inhaled CO2. Intriguingly, progestins stimulate breathing and CO2-chemoreflexes, and the high-affnity ligand etonogestrel (ETO) has been proposed as a treatment option in CCHS. Our objectives were to address two important gaps-in-knowledge: 1) assess ETO’s ability to “rescue” breathing in a rat model of central CO2-chemoreflex impairment, and 2) determine ETO’s site of action. We generated a model of CO2-chemoreflex impairment in adult female Sprague-Dawley rats using targeted injections of substance-P conjugated saporin toxin. Resulting RTN lesions were classified by the number of surviving chemosensitive neurons vs. non-surgical controls. We first administered systemic ETO (acute/vehicle:1h; or chronic/sham: 28 days) and measured resting ventilation and chemoreflexes (hypercapnia, 7.2% CO2; hypoxia, 10% O2) using whole-body plethysmography. In separate ongoing experiments, ETO was infused directly into target brain regions expressing progesterone receptors. We observed a positive relationship between lesion size and CO2-chemoreflex impairment (hypoxic response was intact). Twenty-one days of systemic ETO reversed CO2-impairment selectively in rats with moderate RTN lesions; large-lesion rats were refractory to ETO’s effects. These data suggest that ETO may enhance the CO2-chemoreflex by inducing neuroplasticity in brain structures with connectivity to surviving RTN chemosensitive neurons. Experiments are ongoing to parse out the site of ETO’s restorative action in the brain. T.A.J.:Canadian Lung Association BaO Fellowship, Canadian Institutes of Health Research (CIHR) Postdoctoral Fellowships. S.C.: Canadian Lung Association BaO Fellowship. S.P.: Women and Children’s Health Research Institute Innovation Grant, CIHR Project scheme grant. Nexplanon was kindly donated by Merck through the Investigator-Initiated Study Program (IISP # 55869; SP). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Decreased inhibition of ventral brainstem liver-related neurons in high-fat diet fed mice

Pre-sympathetic liver-related neurons in the ventrolateral and ventromedial medulla (VLM/VMM) participate in the regulation of hepatic carbohydrate and lipid metabolism. Increased sympathetic activity observed in diet-induced obese mice likely contributes to excessive hepatic glucose production, and thus to the development, and/or progression of type 2 diabetes mellitus. At the cellular level, change in neuronal activity and/or synaptic balance is one of the underlying mechanisms that can lead to increased sympathetic outflow. In this study, we tested the hypothesis that high-fat diet (HFD) diminishes glycinergic inhibition of liver-related neurons in the VLM/VMM. We crossed heterozygous glycine transporter 2 Cre (GlyT2Cre) mice with floxed channelrhodopsin 2 (ChR2-EYFP) mice to generate GlyT2-ChR2 expressing mice (GlyT2ChR2/EYFP). Liver-related neurons were identified in the VLM/VMM with a retrograde viral tracer and patch-clamp recordings were conducted. Whole-cell recordings from pre-sympathetic, liver-related neurons revealed that spontaneous inhibitory postsynaptic currents (sIPSCs) are mediated by GABA and glycine. Our data showed that increasing the activity of inhibitory inputs leads to increased glycine release. Next, light stimulation was used to trigger glycine release in GlyT2ChR2/EYFP mice. Light stimulation of ChR2-expressing glycinergic fibers triggered evoked IPSCs (eIPSCs) generated by co-release of GABA and glycine with identical time courses for the two neurotransmitters. Intriguingly, in HFD-fed mice we found that the amplitude of light evoked IPSCs was significantly decreased. These data suggest that liver-related neurons in the VLM/VMM are co-inhibited by GABA and glycine and in HFD-fed mice inhibition of liver-related neurons is reduced. This reduced inhibition of ventral brainstem neurons may contribute to increased sympathetic activity in diet-induced obesity. Supported by: NIDDK122842 and Tulane Brain Institute Marko Spark Innovation Research Fund. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Safety and efficacy of the endoscopic transsphenoidal transclival approach performed using direct cortical stimulation for pontine cavernous malformations.

Surgical treatment of brainstem cavernous malformations (CMs) is challenging. Surgery using the endoscopic transsphenoidal transclival approach (eTSTCA) is reported as a useful alternative for ventral brainstem CMs. However, CMs located in the ventral midline of the brainstem are rare, and only a small number of case reports on these CMs treated with the eTSTCA exist. The efficacy and safety of the eTSTCA have not yet been fully examined. A retrospective analysis was performed for 5 consecutive patients who underwent surgery via the eTSTCA for treating ventral pontine CMs. The average maximum CM diameter was 26.0 mm (18-38 mm). All patients underwent MR-diffusion tensor imaging, which confirmed that the corticospinal tract (CST) deviated posteriorly or laterally to the CM. Direct brainstem cortical stimulation was performed to localize the CST before making the cortical incision. After the excision of the CM, the cavity was filled with artificial CSF to make an aqueous surgical field (wet-field technique) for observing the tumor cavity and confirming complete hemostasis and resection. Total removal was achieved in all patients. The preoperative modified Rankin Scale score was 3 in 3 patients and 4 in 2 patients, whereas it was 1 in 2 patients and 0 in 3 patients 3 months after surgery. Postoperative CSF leakage was observed in 1 patient, and transient abducens nerve palsy was observed in 1 patient. No other intra- or postoperative complications were observed. MR-diffusion tensor imaging and direct brainstem cortical stimulation were useful to ascertain the proximity of the CST to the CM. The endoscope provides a clear view even underwater, and it was safe and effective to observe the entire CM cavity and confirm complete hemostasis without additional retraction of the brainstem parenchyma, including the CST. The eTSTCA provides a direct access point to the lesion and may be a safer alternative treatment for patients whose CST deviates laterally or posteriorly to the CM.

The complete anterior petrosectomy: an expanded extended-middle fossa approach with removal of the infratrigeminal petrous apex and drilling of the lateral clivus.

Intradural exposure in the extended middle fossa anterior transpetrosal approach is traditionally limited to the inferior petrosal sinus inferomedially. Expanding bone removal of the petrous apex around the petrous internal carotid artery (ICA), underneath the trigeminal ganglion/mandibular nerve, and into the lateral component of the clivus can significantly expand the limits of this approach beyond the inferior petrosal sinus and allows for exposure of the midline structures, aspects of the contralateral inferior clival region, and, when high riding, the vertebrobasilar junction. To date, no descriptive techniques for drilling into the lateral clivus in this approach have been published. The authors provide a detailed stepwise description of their complete anterior petrosectomy, in use at their institution, that involves skeletonization of the posteromedial petrous ICA, gentle elevation of the trigeminal ganglion/mandibular nerve, removal of the infratrigeminal petrous apex, and two techniques for drilling into the lateral clivus along the petroclival fissure. These techniques provide a direct and unobstructed corridor to the midpetroclival region and ventral brainstem with greater maneuverability and enhanced control of the midline structures, which is especially useful for resection of petroclival meningiomas, chondrosarcomas, and giant vascular lesions of the mid- and upper basilar artery and its proximal branches.

Medial pontine area: Safe entry to the brainstem as a cut above the rest.

The safe entry zones for ventral brainstem (BS) should ideally be away from the cranial nerve fibers and their nuclei, contain the least amount of fibers, and should be apart from the functional descending and ascending tracts. Specifically, the management of intrinsic lesions located along the anterior surface of the pons has still been controversial, challenging, and worrisome. Our study aims to revisit the fiber-based anatomy of the medial pontine area (MPA), what is presumed to be one of the most commonly used BS safe entry zones in neurosurgery. The six brainstems were kept in 10% formalin solution for at least two months in accordance with the protocol proposed by Klingler J. and Ludwig E. After the arachnoid mater, pia mater, and vascular structures were removed, samples were frozen at -16°C for at least two weeks. White matter (WM) pathways of the BS were explored by gradually using fiber dissections under the surgical microscope. Safe entry zones of the BS were defined and explored with special emphasis on the ventral pontine region and pontomesancephalic junction. The MPA formed a safe surgical field due to the distinct nature of scarcity of fibers on the anterior surface of the pons. MPA's perfect location in between the descending corticospinal tracts and its secure depth back to the anterior limit of the medial lemniscus constructed a surgical asylum for BS safe entry zones. The pivotal position of the MPA has the potential to offer a combined surgical path with superiorly located BS entry zones, thus creating a wider surgical area. Entry to the BS through the MPA increases the surface area that can be accessed in the ventral pons and can be combined with the other described perioculomotor safe regions. Our study may prove helpful for endoscopic endonasal transclival interventions to intrinsic pontine lesions safer.

Endoscopic endonasal transclival clipping of a cerebellar arteriovenous malformation feeding vessel and associated aneurysm; a 2D operative video

Positioned along the ventral surface of the pons, proximal superior cerebellar artery (SCA) aneurysms account for only 1.7% of all intracranial aneurysms [1]. Unlike more commonly encountered basilar artery aneurysms, patients often experience good outcomes when treated via endovascular coiling or surgical clipping [1,2]. These lesions frequently have a lateral projection and paucity of perforator arteries [2]. With further development of endoscopic endonasal techniques, access to this region is possible via a direct frontal exposure to the ventral brainstem, basilar artery and branching vessels. To date, there are only a limited number of reports describing an endoscopic endonasal transclival (EETC) approach for surgical clipping [3–5]. In this operative video, we detail the surgical clipping of a cerebellar arteriovenous malformation feeding vessel and an associated aneurysm using the EETC approach in a 59-year-old woman who presented with sudden onset of a severe headache. The feeding vessel and aneurysm’s midline location, just below the take-off of the SCA made it a good candidate for this surgery. Major steps included in this video include 1) transsphenoidal exposure of and subsequent drilling of the clivus, 2) dural opening into the pre-pontine cistern and dissection of the aneurysm, 3) clipping of the aneurysm, and 4) multi-layered closure of the skull base defect. Overall, the patient tolerated the procedure well and was found to have no residual filling of the aneurysm or the AVM feeding vessel at 2-year follow-up. EETC is a viable surgical option for the treatment of aneurysm located along the midline of the pre-pontine cistern.

An assessment of the effects of neurokinin1 receptor antagonism against nausea and vomiting: Relative efficacy, sites of action and lessons for future drug development.

A broad-spectrum anti-vomiting effect of neurokinin1 receptor antagonists (NK1 RA), shown in pre-clinical animal studies, has been supported by a more limited range of clinical studies in different indications. However, this review suggests that compared with vomiting, the self-reported sensation of nausea is less affected or possibly unaffected (depending on the stimulus) by NK1 receptor antagonism, a common finding for anti-emetics. The stimulus-independent effects of NK1 RAs against vomiting are explicable by actions within the central pattern generator (ventral brainstem) and the nucleus tractus solitarius (NTS; dorsal brainstem), with additional effects on vagal afferent activity for certain stimuli (e.g., highly emetogenic chemotherapy). The central pattern generator and NTS neurones are multifunctional so the notable lack of obvious effects of NK1 RAs on other reflexes mediated by the same neurones suggests that their anti-vomiting action is dependent on the activation state of the pathway leading to vomiting. Nausea requires activation of cerebral pathways by projection of information from the NTS. Although NK1 receptors are present in cerebral nuclei implicated in nausea, and imaging studies show very high receptor occupancy at clinically used doses, the variable or limited ability of NK1 RAs to inhibit nausea emphasizes: (i) our inadequate understanding of the mechanisms of nausea; and (ii) that classification of a drug as an anti-emetic may give a false impression of efficacy against nausea vs. vomiting. We discuss the potential mechanisms for the differential efficacy of NK1 RA and the implications for future development of drugs that can effectively treat nausea, an area of unmet clinical need.

Stem cell-derived brainstem mouse astrocytes obtain a neurotoxic phenotype in vitro upon neuroinflammation

BackgroundAstrocytes respond to injury and disease through a process known as reactive astrogliosis, of which inflammatory signaling is one subset. This inflammatory response is heterogeneous with respect to the inductive stimuli and the afflicted central nervous system region. This is of plausible importance in e.g. traumatic axonal injury (TAI), where lesions in the brainstem carries a particularly poor prognosis. In fact, astrogliotic forebrain astrocytes were recently suggested to cause neuronal death following axotomy. We therefore sought to assess if ventral brainstem- or rostroventral spinal astrocytes exert similar effects on motor neurons in vitro.MethodsWe derived brainstem/rostroventral spinal astrocyte-like cells (ES-astrocytes) and motor neurons using directed differentiation of mouse embryonic stem cells (ES). We activated the ES-astrocytes using the neurotoxicity-eliciting cytokines interleukin- (IL-) 1α and tumor necrosis factor-(TNF-)α and clinically relevant inflammatory mediators. In co-cultures with reactive ES-astrocytes and motor neurons, we assessed neurotoxic ES-astrocyte activity, similarly to what has previously been shown for other central nervous system (CNS) regions.ResultsWe confirmed the brainstem/rostroventral ES-astrocyte identity using RNA-sequencing, immunocytochemistry, and by comparison with primary subventricular zone-astrocytes. Following cytokine stimulation, the c-Jun N-terminal kinase pathway down-stream product phosphorylated c-Jun was increased, thus demonstrating ES-astrocyte reactivity. These reactive ES-astrocytes conferred a contact-dependent neurotoxic effect upon co-culture with motor neurons. When exposed to IL-1β and IL-6, two neuroinflammatory cytokines found in the cerebrospinal fluid and serum proteome following human severe traumatic brain injury (TBI), ES-astrocytes exerted similar effects on motor neurons. Activation of ES-astrocytes by these cytokines was associated with pathways relating to endoplasmic reticulum stress and altered regulation of MYC.ConclusionsVentral brainstem and rostroventral spinal cord astrocytes differentiated from mouse ES can exert neurotoxic effects in vitro. This highlights how neuroinflammation following CNS lesions can exert region- and cell-specific effects. Our in vitro model system, which uniquely portrays astrocytes and neurons from one niche, allows for a detailed and translationally relevant model system for future studies on how to improve neuronal survival in particularly vulnerable CNS regions following e.g. TAI.

Comparison of the Retrosigmoid Suprameatal and Anterior Subtemporal Transpetrosal Approaches After Full Exposure of the Internal Acoustic Meatus.

Surgical approaches to the ventral brainstem and petroclival regions are complex, and standard retrosigmoid and subtemporal approaches are often inadequate. Retrosigmoid suprameatal tubercle (RSMTA) and anterior subtemporal transpetrosal (ASTA) approaches may provide extended surgical exposure with less brain retraction. The objective of this study was to evaluate advantages and disadvantages of RSMTA vs ASTA, and illustrate the surgical corridors and 3-dimensional microsurgical anatomy of the related structures. Four silicone-injected adult cadaver heads (8 sides) were dissected to evaluate the accessibility of lesions located at the petrous apex, ventral brainstem, and pontomedullary region using ASTA and RSTMA. Both ASTA and RSMTA provide access from the petrous apex to the ventral lower pons and pontomedullary junction. A greater extent of safely resected bone was found in ASTA vs RSMTA. ASTA provides a larger surgical view to the ventrolateral midpons, peritrigeminal region, superior neurovascular complex, pontomesencephalic junction, and posterior cavernous sinus. Meanwhile, through cranial nerve V mobilization, RSMTA provides a larger surgical view to the lower half part of the pons, ventrolateral part of the pontomedullary junction, and middle and lower neurovascular structures. The choice of surgical approach is determined by considering the area where the lesion originates, lesion size, the anatomic structures to which it extends, and evaluation of the area that can be surgically exposed. Our study highlights the differences between these approaches and important surgical anatomic considerations.

Bacterial Meningitis, Streptococcus Suis Isolate: A Case Series (P1-10.007)

<h3>Objective:</h3> NA <h3>Background:</h3> Streptococcus Suis is an avoidable infection in humans with exposure/contact of contaminated pigs/pig products causing meningitis and septicemia; loss of hearing is a more frequent complication (Gill, C.O. et al). We present here 2 cases of bacterial meningitis from streptococcus suis infection. A 57-year old male with fever, biparieto-occipital headache, non-rotatory dizziness, vomiting, left ear hearing loss, and decreasing sensorium. He recently ate at a local Samgyupsal place. He was febrile, drowsy, disoriented, had left ear sensorineural hearing loss, and signs of meningeal irritation. On brain MRI, splenium restricted diffusion with bilateral frontal flair hyperintensity without enhancement seen. Blood culture showed streptococcus suis. Cerebrospinal fluid (CSF) was turbid, leukocyte 60 cells/uL, elevated protein and glucose, other CSF studies were unremarkable. He was started on Penicilin G and steroid therapy. A 51-year old female with fever, bi-parietal headache, non-rotatory dizziness, vomiting, hearing loss, and signs of meningeal irritation. She recently ate at a local Samgyupsal place. She was febrile, awake, had right ear sensorineural hearing loss, and signs of meningeal irritation. On brain MRI, there was bilateral cerebral sulci and cerebellar interfoliar spaces diffuse flair hyperintensities with ventral brainstem and leptomeningeal enhancement. CSF was clear with leukocyte 16 cells/uL, elevated protein, and low glucose. Blood and CSF culture showed streptococcus suis; other CSF studies were unremarkable. The patient was started on Penicilin G and steroid therapy. <h3>Design/Methods:</h3> NA <h3>Results:</h3> NA <h3>Conclusions:</h3> Streptococcus suis in humans is acquired from occupational or household exposure to contaminated pigs/pig meat (Huang, Y.T. et al). It is recognized that suboptimal pork preparation/consumption may increase the risk of acquiring this disease, as our cases above. The treatment principles in bacterial meningitis are mostly the same regardless of the isolate. The treatment with steroids is still controversial however there are studies that show improvement in the patient’s hearing and dizziness. <b>Disclosure:</b> Ms. Abbot has nothing to disclose. Dr. Ng has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Unilab. Dr. Ng has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Menarini. Dr. Ng has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Torrent Pharma. Samantha Anne Gutierrez has nothing to disclose.

High-Fat Diet Modulates the Excitability of Neurons within the Brain-Liver Pathway.

Stimulation of hepatic sympathetic nerves increases glucose production and glycogenolysis. Activity of pre-sympathetic neurons in the paraventricular nucleus (PVN) of the hypothalamus and in the ventrolateral and ventromedial medulla (VLM/VMM) largely influence the sympathetic output. Increased activity of the sympathetic nervous system (SNS) plays a role in the development and progression of metabolic diseases; however, despite the importance of the central circuits, the excitability of pre-sympathetic liver-related neurons remains to be determined. Here, we tested the hypothesis that the activity of liver-related neurons in the PVN and VLM/VMM is altered in diet-induced obese mice, as well as their response to insulin. Patch-clamp recordings were conducted from liver-related PVN neurons, VLM-projecting PVN neurons, and pre-sympathetic liver-related neurons in the ventral brainstem. Our data demonstrate that the excitability of liver-related PVN neurons increased in high-fat diet (HFD)-fed mice compared to mice fed with control diet. Insulin receptor expression was detected in a population of liver-related neurons, and insulin suppressed the firing activity of liver-related PVN and pre-sympathetic VLM/VMM neurons in HFD mice; however, it did not affect VLM-projecting liver-related PVN neurons. These findings further suggest that HFD alters the excitability of pre-autonomic neurons as well as their response to insulin.

Endoscopic endonasal transclival approach for a ventral brainstem epidermoid cyst: illustrative case.

Intracranial epidermoid cysts are benign, slow-growing malformations that most commonly arise at the skull base. Maximizing resection of the cyst contents and the capsule reduces long-term recurrence but can be made difficult by cyst wall adherence to critical neurovascular structures. Expanded endonasal approaches (EEAs) offer an alternative to traditional open transcranial approaches for accessible epidermoid cysts. In this case report, the authors demonstrate a transclival EEA for a large, ventral brainstem epidermoid cyst. A 41-year-old woman who presented with progressive headaches, diplopia, malaise, and fatigue was found to have a 4.7-cm midline, ventral brainstem epidermoid cyst. She underwent an expanded endonasal transclival approach that exposed the brainstem from the level of the dorsum sella to the tip of the basion. A near-total resection was completed with removal of all cyst contents and most of the capsular wall. Reconstruction was completed with Duragen, an autologous fat graft, and a nasoseptal flap. Postoperatively, she had a partial left cranial nerve VI palsy that remained stable 8 weeks after surgery. The expanded endoscopic transclival approach can facilitate effective resection of midline, ventral epidermoid cysts.

A lower motor neuron disease in takahē (Porphyrio hochstetteri) is an endoplasmic reticulum storage disease

Aims: To investigate the pathogenesis of a disease in takahē with intracytoplasmic inclusion bodies in lower motor neurons. Methods: Four cases aged between 5 and 12 years, from three different wildlife sanctuaries in New Zealand were examined. Of these, only one had signs of spinal dysfunction in the form of paresis. Stained paraffin sections of tissues were examined by light microscopy and immunostained sections of the ventral horn of the spinal cord by confocal microscopy. Epoxy resin sections of the bird with spinal dysfunction were examined by electron microscopy. Results: Two types of inclusion bodies were noted, but only in motor neurons of the ventral spinal cord and brain stem. These were large globoid eosinophilic bodies up to 5 µm in diameter, and yellow/brown granular inclusions mostly at the pole of the cell. The globoid bodies stained with Luxol fast blue but not with periodic acid Schiff (PAS), or Sudan black. The granular inclusions stained with Luxol fast blue, PAS and Sudan black. Both bodies were slightly autofluorescent. On electron microscopy the globoid bodies had an even electron-dense texture and were bound by a membrane. Beneath the membrane were large numbers of small intraluminal vesicles. The smaller granular bodies were more heterogeneous, irregularly rounded and membrane-bound accumulations of granular electron-dense material, often with electron-lucent vacuoles. Others were more vesicular but contained varying amounts of electron-dense material. The large globoid bodies did not immunostain for lysosomal markers lysosomal associated protein 1 (LAMP1) or cathepsin D so they were not lysosomal. The small granular bodies stained for cathepsin D by a chromogenic method. A kindred matrix analysis showed two cases to be as closely related as first cousins, and another case was almost as closely related to one of them, but the fourth bird was unrelated to any other. Conclusions: It was concluded that this was an endoplasmic reticulum storage disease due to a specific protein misfolding within endoplasmic reticulum. It was rationalised that the two types of inclusions reflected the same aetiology, but that misfolded protein in the smaller granular bodies had entered the lysosomal system via endoplasmic reticulum autophagy. Although the cause was unclear, it most likely had a genetic aetiology or predisposition and, as such, has clinical relevance.

Real-time ultrasound guidance in the endoscopic endonasal resection of a retro-odontoid pannus: Technical note and case illustration.

Odontoidectomy is a surgical procedure indicated in the setting of various pathologies, with the main goal of decompressing the ventral brain stem and spinal cord as a result of irreducible compression at the craniovertebral junction. The endoscopic endonasal approach has been increasingly used as an alternative to the transoral approach as it provides a straightforward, panoramic, and direct approach to the odontoid process. In addition, intraoperative ultrasound (US) guidance is a technique that can optimize safety and surgical outcomes in this context. It is used as an adjunct to neuronavigation and provides intraoperative confirmation of decompression of craniovertebral junction structures in real time. The authors aim to present the use and safe application of real-time intraoperative US guidance during endonasal endoscopic resection of a retro-odontoid pannus. A retrospective chart review of a single case was performed and presented herein as a case report and narrated operative video. A minimally invasive US transducer was used intraoperatively to guide the resection of a retro-odontoid pannus and confirm spinal cord decompression in real time. Postoperative examination of the patient revealed immediate neurological improvement. Intraoperative ultrasonography is a well described and useful modality in neurosurgery. However, the use of intraoperative US guidance during endonasal endoscopic approaches to the craniovertebral junction has not been previously described. As demonstrated in this technical note, the authors show that this imaging modality can be added to the ever-evolving armamentarium of neurosurgeons to safely guide the decompression of neural structures within the craniocervical junction with good surgical outcomes.

Management of Ventral Brainstem Compression in Chiari Malformation Type I.

Craniovertebral junction (CVJ) abnormalities are associated with the Chiari malformation type I. These abnormalities may lead to ventral brainstem compression which can be reduced with traction and posterior reduction using instrumentation. In other cases, the irreducible CVJ pathology with persistent ventral brainstem compression requires ventral decompression. In all cases, a posterior extradural or extra-intradural decompression is required along with an occipitocervical fusion to maintain the reduced and realigned CVJ or stabilize the CVJ after a ventral decompression.

Transcervical, retropharyngeal odontoidectomy - Anatomical considerations.

Anterior craniocervical junction lesions have always been a challenge for neurosurgeons. Presenting with lower cranial nerve dysfunction and symptoms of brainstem compression, decompression is often required. While posterior approaches offer indirect ventral brainstem decompression, direct decompression via odontoidectomy is necessary when they fail. The transoral and endoscopic endonasal approaches have been explored but come with their own limitations and risks. A novel retropharyngeal approach to the cervical spine has shown promising results with reduced complications. This study aims to explore the feasibility and potential advantages of the anterior retropharyngeal approach for accessing the odontoid process. To investigate the anatomical aspects of the anterior retropharyngeal approach, a paramedian skin incision was performed below the submandibular gland on two cadaveric specimens. The subcutaneous tissue followed by the platysma is dissected, and the superficial fascial layer is opened. The plane between the vascular sheath laterally and the pharyngeal structures medially is entered below the branching point of the facial vein and internal jugular vein. After reaching the prevertebral plane, further dissection cranially is done in a blunt fashion below the superior pharyngeal nerve and artery. Various anatomical aspects were highlighted during this approach. The anterior, submandibular retropharyngeal approach to the cervical spine was performed successfully on two cadavers highlighting relevant anatomical structures, including the carotid artery and the glossopharyngeal, hypoglossal, and vagus nerves. This approach offered wide exposure, avoidance of oropharyngeal contamination, and potential benefit in repairing cerebrospinal fluid fistulas. For accessing the craniocervical junction, the anterior retropharyngeal approach is a viable technique that offers many advantages. However, when employing this approach, surgeons must have adequate anatomical knowledge and technical proficiency to ensure better outcomes. Further studies are needed to enhance our anatomical variations understanding and reduce intraoperative risks.

Use of multi-perturbation Shapley analysis in lesion studies of functional networks: The case of upper limb paresis.

Understanding the impact of variation in lesion topography on the expression of functional impairments following stroke is important, as it may pave the way to modeling structure-function relations in statistical terms while pointing to constraints for adaptive remapping and functional recovery. Multi-perturbation Shapley-value analysis (MSA) is a relatively novel game-theoretical approach for multivariate lesion-symptom mapping. In this methodological paper, we provide a comprehensive explanation of MSA. We use synthetic data to assess the method's accuracy and perform parameter optimization. We then demonstrate its application using a cohort of 107 first-event subacute stroke patients, assessed for upper limb (UL) motor impairment (Fugl-Meyer Assessment scale). Under the conditions tested, MSA could correctly detect simulated ground-truth lesion-symptom relationships with a sensitivity of 75% and specificity of ~90%. For real behavioral data, MSA disclosed a strong hemispheric effect in the relative contribution of specific regions-of-interest (ROIs): poststroke UL motor function was mostly contributed by damage to ROIs associated with movement planning (supplementary motor cortex and superior frontal gyrus) following left-hemispheric damage (LHD) and by ROIs associated with movement execution (primary motor and somatosensory cortices and the ventral brainstem) following right-hemispheric damage (RHD). Residual UL motor ability following LHD was found to depend on a wider array of brain structures compared to the residual motor ability of RHD patients. The results demonstrate that MSA can provide a unique insight into the relative importance of different hubs in neural networks, which is difficult to obtain using standard univariate methods.