Remyelination Improves Voiding Dysfunction in a Mouse Model of Multiple Sclerosis

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Of note, over 80% of MS patients have urinary symptoms as one of their earliest symptoms. Since MS patients often live into older age, urinary incontinence and retention are significant problems affecting their quality of life. Although several studies show that inflammatory-demyelinating animal models of MS develop bladder dysfunction, the confounding influence of systemic inflammation in these models limits potential interpretation on the contribution of CNS-myelination to bladder dysfunction. We sought to address this knowledge gap using the cuprizone model of demyelination and remyelination. C57Bl/6 mice were treated with dietary cuprizone (0.2%w/w) for four weeks to induce demyelination. One group was allowed four additional weeks for recovery and remyelination. We performed voiding spot assay (VSA), urethane-anesthetized cystometry, and CNS-histology to assess demyelination-induced differences in urinary performance. We observed that cortical demyelination causes significant aberrance in voiding behavior (conscious cortical control) characterized by increased micturition frequency and reduced volume per micturition. Interestingly, remyelination restored healthy bladder function. However, there were no significant changes in the cystometric parameters (brainstem reflex) between the treatment groups. While MS is not classically considered a disease of aging, extending the longevity of these patients has not been reciprocated with improved treatments for their most-bothersome conditions, notably urinary symptoms that persist throughout life. Our data represent a novel compelling connection and strong correlation between CNS-myelination and cortical control of bladder function, which has potential implications in MS, aging, and aging-associated neurological disorders.

Penanganan Trigeminocardiac Reflex (TCR) selama Anestesi untuk Bedah Saraf

Trigeminocardiac reflex (TCR) is a unique brain stem reflex that manifests as negative cardio-respiratory perturbations. The trigeminocardiac reflex (TCR) is defined as the sudden onset of parasympathetic dysrhythmia, sympathetic hypotension, apnea, or gastric hypermotility during stimulation of any of the sensory branches of the trigeminal nerve. Clinically, the TCR has been reported in all the surgical procedures in which a structure innervated by the trigeminal nerve is involved. This reflex is largely reported in skull base surgeries/interventions; however, in recent times, it has been also linked with many neurosurgical, neurointerventional procedures, non-neurosurgical and non-surgical conditions. This reflex presents with many cardiovascular changes that can create catastrophic complications, worse outcome as well as diagnostic dilemmas. Although, there is an abundant literature with reports of incidences and risk factors of the TCR; the physiological significance and function of this brainstem reflex has not yet been fully elucidated. In addition, there are complexities within the TCR that requires examination and clarification. If a CTR occurs, it can risk factor identification and modification, depth of anesthesia assessment, prophylactic treatment with either vagolytic agents or peripheral nerve block in case of peripheral manipulations of the nerve, careful cardiovascular monitoring during anesthesia, especially in those with a risk factor for TCR, treatment of the condition when it occurs: cessation of the manipulation, and administration of vagolytic agents and adrenaline. Therefore, this narrative review intends to elaborate on its mechanisms, definition, pathophysiology, manifestations, diagnosis and management.

Efficacy of transcutaneous cardiac pacing for transient asystole caused by trigeminocardiac reflex: illustrative case

BACKGROUND Trigeminocardiac reflex (TCR) is a brainstem reflex caused by stimulation of the trigeminal nerve, which results in bradycardia, hypotension, and asystole. TCR can occur during any neurosurgical procedure. Initially, it is managed via the immediate removal of the stimulus from the trigeminal nerve. If asystole persists after intravenous atropine or glycopyrrolate, chest compression or transcutaneous cardiac pacing may be considered. The authors present the first case of TCR that was successfully managed with transcutaneous cardiac pacing. OBSERVATIONS A 51-year-old man presented with aneurysmal subarachnoid hemorrhage. Although he had no history of cardiac disease and there were no abnormal findings on electrocardiography, transient asystole due to TCR occurred during craniotomy. The patient’s heart rate spontaneously recovered after the immediate discontinuation of the procedure. The authors completed aneurysm clipping with transcutaneous cardiac pacing because intravenous atropine was not effective in preventing TCR. There were no complications associated with intraoperative asystole or transcutaneous cardiac pacing, and the patient was discharged without neurological deficits. LESSONS TCR can be appropriately managed with the immediate discontinuation of intraoperative procedures. Furthermore, transcutaneous cardiac pacing may be considered for persistent TCR with poor response to intravenous atropine or glycopyrrolate.

A potential new brainstem reflex: The oculoglossal phenomenon

Background: A synchronized involuntary movement of the tongue to the same side as voluntary movements of the eyes, termed the oculoglossal phenomenon, has been observed. A description of the hypothesized pathway of this phenomenon could guide the development of a rapid clinical evaluation of the long segment of the brainstem and help facilitate further studies to establish a new reflex, if possible. The aim of this study is to describe and propose the simple concept of this pathway/phenomenon, the oculoglossal phenomenon. Methods: This is an observational study. Of a newly observe brainstem phenomenon evaluated on a subject at the National Neuroscience Institute in king Fahad Medical City (KFMC), Riyadh, Saudi Arabia. After being observed incidentally in a single patient, 60 participants were tested between January and March 2020 to confirm the presence of the phenomenon. Each subject was instructed to protrude the tongue and then move their eyes horizontally to the side. If the tongue simultaneously and involuntarily moved to the same side as the eyes, the test was deemed confirmatory. A literature review was performed, and possible anatomical pathway was proposed. Results: The oculoglossal reflex was present in most (50/60, 83.3%) of the subjects. Our proposed pathway begins at the frontal cortex, followed by a projection to the paramedian pontine reticular formation, then to the contralateral medial longitudinal fasciculus and bilaterally to the hypoglossal nuclei. Conclusion: An accurate description of this phenomenon could lead to additional studies and possibly establishing it as a legitimate reflex, thus conceivably adding a new tool in the neurological examination to evaluate the brainstem’s integrity.

Brainstem neuropathology in two cases of COVID-19: SARS-CoV-2 trafficking between brain and lung

Introduction SARS-CoV-2 might spread through the nervous system, reaching respiratory centers in the brainstem. Because we recently reported neurophysiological brainstem reflex abnormalities in COVID-19 patients, we here neuropathologically assessed structural brainstem damage in two COVID-19 patients. Materials and methods We assessed neuropathological features in two patients who died of COVID-19 and in two COVID-19 negative patients as controls. Neuronal damage and corpora amylacea (CA) numbers /mm2 were histopathologically assessed. Other features studied were the immunohistochemical expression of the SARS-CoV-2 nucleoprotein (NP) and the Iba-1 antigen for glial activation. Results Autopsies showed normal gross brainstem anatomy. Histopathological examination demonstrated increased neuronal and CA damage in Covid-19 patients’ medulla oblongata. Immunohistochemistry disclosed SARS-CoV-2 NP in brainstem neurons and glial cells, and in cranial nerves. Glial elements also exhibited a widespread increase in Iba-1 expression. Sars-Co-V2 was immunohistochemically detected in the vagus nerve fibers. Discussion Neuropathologic evidence showing SARS-CoV-2 in the brainstem and medullary damage in the area of respiratory centers strongly suggests that the pathophysiology of COVID-19-related respiratory failure includes a neurogenic component. Sars-Co-V2 detection in the vagus nerve, argues for viral trafficking between brainstem and lung.

Effect of Aging, Gender and Sensory Stimulation of TRPV1 Receptors with Capsaicin on Spontaneous Swallowing Frequency in Patients with Oropharyngeal Dysphagia: A Proof-of-Concept Study

Spontaneous swallowing contributes to airway protection and depends on the activation of brainstem reflex circuits in the central pattern generator (CPG). We studied the effect of age and gender on spontaneous swallowing frequency (SSF) in healthy volunteers and assessed basal SSF and TRPV1 stimulation effect on SSF in patients with post-stroke oropharyngeal dysphagia (OD). The effect of age and gender on SSF was examined on 141 healthy adult volunteers (HV) divided into three groups: GI—18–39 yr, GII—40–59 yr, and GIII—>60 yr. OD was assessed by the Volume–Viscosity Swallowing Test (VVST). The effect of sensory stimulation with capsaicin 10−5 M (TRPV1 agonist) was evaluated in 17 patients with post-stroke OD, using the SSF. SSF was recorded in all participants during 10 min using surface electromyography (sEMG) of the suprahyoid muscles and an omnidirectional accelerometer placed over the cricothyroid cartilage. SSF was significantly reduced in GII (0.73 ± 0.50 swallows/min; p = 0.0385) and GIII (0.50 ± 0.31 swallows/min; p < 0.0001) compared to GI (1.03 ± 0.62 swallows/min), and there was a moderate significant correlation between age and SFF (r = −0.3810; p < 0.0001). No effect of gender on SSF was observed. Capsaicin caused a strong and significant increase in SSF after the TRPV1 stimulation when comparing to basal condition (pre-capsaicin: 0.41 ± 0.32 swallows/min vs post-capsaicin: 0.81 ± 0.51 swallow/min; p = 0.0003). OD in patients with post-stroke OD and acute stimulation with TRPV1 agonists caused a significant increase in SSF, further suggesting the potential role of pharmacological stimulation of sensory pathways as a therapeutic strategy for CPG activation in patients with OD.

Trigeminocardiac Reflex Induced by Maxillary Nerve Stimulation during Sphenopalatine Ganglion Implantation: A Case Series

Background: The trigeminocardiac reflex (TCR) is a brainstem reflex following stimulation of the trigeminal nerve, resulting in bradycardia, asystole and hypotension. It has been described in maxillofacial and craniofacial surgeries. This case series highlights TCR events occurring during sphenopalatine ganglion (SPJ) neurostimulator implantation as part of the Pathway CH-2 clinical trial “Sphenopalatine ganglion Stimulation for Treatment of Chronic Cluster Headache”. Methods: This is a case series discussing sphenopalatine ganglion neurostimulator implantation in the pterygopalatine fossa as treatment for intractable cluster headaches. Eight cases are discussed with three demonstrating TCR events. All cases received remifentanil and desflurane for anesthetic maintenance. Results: Each patient with a TCR event experienced severe bradycardia. In two cases, TCR resolved with removal of the introducer, while the third case’s TCR event resolved with both anticholinergic treatment and surgical stimulation cessation. Conclusion: Each TCR event occurred before stimulation of the fixed introducer device, suggesting the cause for the TCR events was mechanical in origin. Due to heightened concern for further TCR events, all subsequent cases had pre-anesthesia external pacing pads placed. Resolution can occur with cessation of surgical manipulation and/or anticholinergic treatment. Management of TCR events requires communication between surgical teams and anesthesia providers, especially during sphenopalatine ganglion implantation when maxillary nerve stimulation is possible.

Perceptual gating of a brainstem reflex facilitates speech understanding in humans

Navigating “cocktail party” situations by enhancing foreground sounds over irrelevant background information is typically considered from a cortico-centric perspective. However, subcortical circuits, such as the medial olivocochlear reflex (MOCR) that modulates inner ear activity itself, have ample opportunity to extract salient features from the auditory scene prior to any cortical processing. To understand the contribution of auditory subcortical nuclei and the cochleae, physiological recordings were made along the auditory pathway while listeners differentiated non(sense)-words and words. Both naturally-spoken and intrinsically-noisy, vocoded speech — filtering that mimics processing by a cochlear implant—significantly activated the MOCR, whereas listening to speechin-background noise revealed instead engagement of midbrain and cortical resources. An auditory periphery model reproduced these speech degradation-specific effects, providing a rationale for goal-directed MOCR gating to enhance representation of speech features in the auditory nerve. These results highlight two strategies co-existing in the auditory system to accommodate categorically different speech degradations.

Sudden arrhythmia followed by bradycardia during sagittal split ramus osteotomy: trigeminocardiac reflex

Trigeminocardiac reflex (TCR) is a brainstem reflex triggered by the stimulation of any branch of the fifth cranial nerve along its course, presenting as a reduction in heart rate and blood pressure. Oculocardiac reflex is a well-known subtype of TCR. In the case reported here, remarkable arrhythmia followed by bradycardia occurred suddenly in a healthy patient undergoing orthognathic surgery. The heart rhythm recovered when the surgical manipulation ceased, but bradycardia was reproduced when the surgery resumed. This case of TCR is unique in that remarkable arrhythmia first appeared and led to bradycardia; accordingly, intravenous lidocaine and an anticholinergic agent were administered simultaneously instead of anticholinergic agents alone, and were protective. Although TCR rarely occurs during orthognathic surgery, clinicians should be aware of its possibility and able to judge and manage it promptly.