The Vagus Nerve Somatosensory-evoked Potential in Neural Disorders: Systematic Review and Illustrative Vignettes.

Objective. To review the scientific publications reporting vagal nerve somatosensory-evoked potential (VSEP) findings from individuals with brain disorders, and present novel physiological explanations on the VSEP origin. Methods. We did a systematic review on the papers reporting VSEP findings from individuals with brain disorders and their controls. We evaluated papers published from 2003 to date indexed in PubMed, Web of Science, and Scielo databases. We extracted the following information: number of patients and controls, type of neural disorder, age, gender, stimulating/recording and grounding electrodes as well as stimulus side, intensity, duration, frequency, and polarity. Information about physiological parameters, neurobiological variables, and correlation studies was also reviewed. Representative vignettes were included to add support to our conclusions. Results. The VSEP was studied in 297 patients with neural disorders such as Parkinson's disease (PD), Alzheimer's disease, vascular dementia, mild cognitive impairment, subjective memory impairment, major depression, and multiple sclerosis. Scalp responses marked as the VSEP showed high variability, low validity, and poor reproducibility. VSEP latencies and amplitudes did not correlate with disease duration, unified PD rating scale score, or heart function in PD patients nor with cerebrospinal fluid ß amyloid, phosphor-τ, and cognitive tests from patients with mental disorders. Vignettes demonstrated that the VSEP was volume conduction propagating from muscles surrounding the scalp recording electrodes. Conclusion. The VSEP is not a brain-evoked potential of neural origin but muscle activity induced by electrical stimulation of the tragus region of the ear. This review and illustrative vignettes argue against assessing the parasympathetic system using the so-called VSEP.

Combined Presigmoid-Subtemporal Approach in a Semi-Sitting Position for Petroclival Meningiomas: A Technical Report.

The removal of petroclival meningiomas (PMs) is considered a neurosurgical challenge due to the critical mobilization of key neurovascular structures. Limited knowledge about the benefits of operating on patients with PMs using the combined presigmoid-subtemporal approach (CPSA) in a semi-sitting position has precluded its generalizability. We report on ten patients with PMs operated in a semi-sitting position using CPSA. We remark that before the surgical approach was accomplished in our group of patients, the CPSA via semi-sitting position was conducted and standardized in six adult cadaveric heads. The neuroanatomic dissections made in cadavers allowed us to confidently use CPSA in our set of patients. There were no comorbidities, perioperative complications, or deaths associated with the surgical procedure. CPSA via a semi-sitting position can be considered a safe approach to remove PMs.

The vagus nerve somatosensory evoked potential in the intact brain: state-of-evidence and some representative vignettes.

OBJECTIVE: Scalp-recorded evoked potentials elicited by applying afferent electrical stimulation at the tragus region of the human external ear have shown inconsistent results. We aim to disentangle discrepant findings and interpretations, and put forward novel physiological explanations on the origin of the vagus nerve somatosensory evoked potentials (VSEP). METHODS: We systematically search and critically appraise in PubMed, Web of Science, and Scielo databases the scientific reports publishing VSEP findings elicited by afferent electrical stimulation at the tragus region from individuals without brain disorders. Eligible studies published from January 2000 to April 2020 were extracted. The following information was identified from each article: number of participants; age; gender; stimulating/recording and grounding electrodes as well as stimulus side, intensity, duration, frequency, and polarity. Information about physiological parameters and neurobiological variables was also extracted. Representative vignettes with novel scalp responses induced by stimulating the tragus were also included to add support to our conclusions. RESULTS: 140 healthy participants were identified from six selected reports. Mean age ranged from 24.3 to 61.5 years. Stimulating and recording aspects were miscellaneous among studies. Scalp responses marked as the VSEP were recorded in 76% of participants, and showed high variability, low validity and poor reproducibility. Age correlated with response latencies. There were not gender differences in scalp response parameters. Cardiovascular function was unaltered by tragus stimulation. Vignettes showed that the VSEP was scalp muscle responses. CONCLUSION: VSEP did not fulfil evoked potential guidelines. VSEP corresponded to volume conduction propagating from muscles surrounding scalp recording sites.

Territorial and Extraterritorial Trigeminocardiac Reflex: A Review for the Neurosurgeon and a Type IV Reflex Vignette.

The trigeminocardiac reflex (TCR) is a complex and, sometimes, fatal event triggered by overstimulation of the trigeminal nerve (TN) and its territorial and spinal cord branches. We reviewed and compiled for the neurosurgeon key aspects of the TCR that include a novel and straightforward classification, as well as morphophysiology, pathophysiology, neuromonitoring and neuromodulation features. Further, we present intraoperative data from a patient who developed extraterritorial, or type IV, TCR while undergoing a cervical surgery. TCR complexity, severity and unwanted outcomes indicate that this event should not be underestimated or overlooked in the surgical room. Timely TCR recognition in surgical settings is valuable for applying effective intraoperative management to prevent catastrophic outcomes.

Cranial nerve 13.

Contrary to popular belief, there are 13 cranial nerves. The thirteenth cranial nerve, commonly referred to as the nervus terminalis or terminal nerve, is a highly conserved multifaceted nerve found just above the olfactory bulbs in humans and most vertebrate species. In most forms its fibers course from the rostral portion of the brain to the olfactory and nasal epithelia. Although there are differing perspectives as to what constitutes this nerve, in most species GnRH-immunoreactive neurons appear to be its defining feature. The involvement of this trophic peptide, as well as the nerve's association with the development of the hypothalamic-pituitary-gonadal axis, suggest a primary role in reproductive development and, in humans, disorders such as Kallmann syndrome. In some species, this enigmatic nerve appears to influence sensory processing, sexual behavior, autonomic and vasomotor control, and pathogenic defense (via secretion of nitric oxide). In this review, we provide a general overview of what is known about this neglected cranial nerve, with the goal of informing neurologists and neuroscientists of its presence and the need for its further study.

Neurophysics Assessment of the Muscle Bioenergy Generated by Transcranial Magnetic Stimulation.

The content of the rectified motor evoked potential (MEP) induced by transcranial magnetic stimulation (TMS) has ambiguously been assessed without the precision that energy calculation deserves. This fact has misled data interpretation and misguided biomedical interventions. To definitively fill the gap that exits in the neurophysics processing of these signals, we computed, in Walls ( W ^ ), the bioenergy within the rectified MEP recorded from the human first digitorum index (FDI) muscle at rest and under isometric contraction. We also gauged the biowork exerted by this muscle. Here we show that bioenergy and biowork can accurately and successfully be assessed, validated, and determined in W ^ from MEP signals induced by TMS, regardless of knowing the mathematical expression of the function of the signal. Our novel neurophysics approach represents a dramatic paradigm shift in analysis and interpretation of the content of the MEP and will give a true meaning to the content of rectified signals. Importantly, this innovative approach allowed unveiling that women exerted more bioenergy than men at the magnetic stimulations used in this study. Revisitation of conclusions drawn from studies published elsewhere assessing rectified EMG signals that have used ambiguous units is strongly recommended.

Prognostic factors for overall survival in patients with chronic myeloid leukemia treated with imatinib at the National Cancer Institute - Mexico, from 2000 to 2016.

To determine potential predictors of long-term survival in a large set of Hispanic (Mexican) patients with chronic myeloid leukemia (CML) treated with imatinib. We conducted an analysis with data from 411 patients with CML treated at the National Cancer Institute - Mexico, between January 2000 and December 2016. We found a median age at diagnosis of 40 years (range: 18-84 years). The survival rate at 150 months was 82.02%, and we found that phase at diagnosis (ß: 0.447, 95% Confidence Interval [95% CI]: 0.088, 0.806; P = 0.015), prognostic scales (Sokal [P = 0.021] and Hasford [ß: 0.369, 95% CI: 0.049, 0.688; P = 0.024]) and hematological response at 3 months (ß: 0.717, 95% CI: 0.443, 0.991; P < 0.001), but not molecular response (P = 0.834 for 6 months, P = 0.927 for 12 months, P = 0.250 for 18 months), were independently associated with overall survival. Survival analysis in subsets, according to the initial phase (chronic, accelerated and blastic phase) did not show any effect according to prognostic scales (P > 0.05). Mexican patients with CML have repeatedly been diagnosed at earlier ages. Prognostic factors in CML may differ according to the ethnic or geographical context. We found that phase at diagnosis, prognostic scale and hematological response at 3 months were independent predictors of survival.

Smell status in functional movement disorders: New clues for diagnosis and underlying mechanisms.

OBJECTIVE: Functional movement disorders (FMDs) mimic a range of movements, neuropsychiatric and neurodegenerative disorders known to have smell dysfunction, which has been neglected in terms of its application to FMD. We aim to determine the smell status in FMD patients tested by a non-invasive, reliable and validated olfactory test. PATIENTS AND METHODS: We quantitatively assessed in thirty-five FMD patients their smell status and compared it to that of healthy age- and sex-matched controls, and of patients with Parkinson's disease (PD). All participants were administered the Brief Smell Identification Test (B-SIT), a standardized short version of the University of Pennsylvania Smell Identification Test (UPSIT). The Picture Identification Test (PIT), a visual test analogous in content and form to the UPSIT designed to control for non-olfactory cognitive confounds, was also administered. RESULTS: The B-SIT scores of the FMD patients were higher than those from PD patients [respective means (standard deviations: SDs) = FMD, 9.54 (1.57); PD, 4.64 (1.05), p < 0.01)] but similar to the smell scores from healthy controls [9.97 (1.77), p = 0.35]. Gender, age, time of disease onset, smoking status, and phenotypic expression did not influence the test scores. Fourteen FMD patients who mentioned having olfactory dysfunction before smell testing have their test results within normal range. PIT scores from patients and healthy controls were within normal range. CONCLUSIONS: These findings indicate that FMD patients have normal olfactory function. Olfactory testing may be helpful in identifying and differentiating FMD from other movement, neurodegenerative and neuropsychiatric diseases for which smell function is altered.

The Three Nociceptive Responses of the Orbicularis Oculi Reflex in Alzheimer's Disease: State of the Evidence and Meta-analysis.

There is an emerging belief that electrically elicited blink reflexes (BR) may distinguish Alzheimer's disease (AD) from other disorders characterized by memory dysfunction. To qualitatively and quantitatively distinguish the effects that electrical stimulation has over the blink reflex (eBR) recorded from patients with AD and healthy controls (HCs), we did a systematic review of the literature, and conducted a meta-analysis. Following our selected criteria, 94 AD patients and 97 HCs were identified from articles published in English between 1950 and 2017. Although the 3 responses (R1, R2 and R3) of the eBR were studied in a number of patients, only the R2 response was quantified in all studies. Thresholds and stimulation intensities parameters were found to be used in a miscellaneous form, and the majority of times, such parameters deviated from validated guidelines. The stimulation frequencies used to elicit the BR responses ranged between 0.14 and 0.2 Hz. These frequencies favored HCs compared with AD patients (odds ratio = 1.08; 95% CI = 0.30-1.85), I2 = 0% [P = .99]; Q = 271.89 [df = 7, P < .000]). Egger's regression test suggested publication bias (intercept = 32.38; 95% CI = -8.98 to -3.2; P = .001). Our results unveiled key shortcomings in the data reported; such shortcomings need to be corrected in future AD research looking for obtaining more reliable and reproducible eBR studies; otherwise, interventions may be misleading.

Evidences in Neurological Surgery and a Cutting Edge Classification of the Trigeminocardiac Reflex: A Systematic Review.

BACKGROUND: The trigeminocardiac reflex (TCR) is characterized by bradycardia, decrease of mean arterial blood pressure, and sometimes, asystole during surgery. We critically reviewed TCR studies and devised a novel classification scheme for assessing the reflex. METHODS: A comprehensive systematic literature review was performed using PubMed, MEDLINE, Web of Science, EMBASE, and Scielo databases. Eligible studies were extracted based on stringent inclusion and exclusion criteria. Statistical analyses were used to assess cardiovascular variables. TCR was classified according to morphophysiologic aspects involved with reflex elicitation. RESULTS: A total of 575 patients were included in this study. TCR was found in 8.9% of patients. The reflex was more often triggered by interventions made within the anterior cranial fossa. The maxillary branch (type II in the new classification) was the most prevalent nerve branch found to trigger the TCR. Heart rate and mean arterial blood pressure were similarly altered (P = 0.06; F = 0.3912809), covaried with age (P = 0.012; F = 9.302), and inversely correlated to each other (r = -0.27). CONCLUSIONS: TCR is a critical cardiovascular phenomenon that must be quickly identified and efficiently classified and should trigger vigilance. Prompt therapeutic measures during neurosurgical procedures should be carefully addressed to avoid unwanted complications. Accurate categorization using the new classification scheme will help to improve understanding and guide the management of TCR in the perioperative period.

Modulation of the ultradian human nasal cycle by sleep stage and body position.

OBJECTIVE:: The nasal cycle, which is present in a significant number of people, is an ultradian side-to-side rhythm of nasal engorgement associated with cyclic autonomic activity. We studied the nasal cycle during REM/non-REM sleep stages and examined the potentially confounding influence of body position on lateralized nasal airflow. METHODS:: Left- and right-side nasal airflow was measured in six subjects during an eight-hour sleep period using nasal thermistors. Polysomnography was performed. Simultaneously, body positions were monitored using a video camera in conjunction with infrared lighting. RESULTS:: Significantly greater airflow occurred through the right nasal chamber (relative to the left) during periods of REM sleep than during periods of non-REM sleep (p<0.001). Both body position (p < 0.001) and sleep stage (p < 0.001) influenced nasal airflow lateralization. CONCLUSIONS:: This study demonstrates that the lateralization of nasal airflow and sleep stage are related. Some types of asymmetrical somatosensory stimulation can alter this relationship.

Modulation of the ultradian human nasal cycle by sleep stage and body position / Modulação do ciclo nasal humano ultradiano pelo estágio do sono e a posição corporal

ABSTRACT Objective: The nasal cycle, which is present in a significant number of people, is an ultradian side-to-side rhythm of nasal engorgement associated with cyclic autonomic activity. We studied the nasal cycle during REM/non-REM sleep stages and examined the potentially confounding influence of body position on lateralized nasal airflow. Methods: Left- and right-side nasal airflow was measured in six subjects during an eight-hour sleep period using nasal thermistors. Polysomnography was performed. Simultaneously, body positions were monitored using a video camera in conjunction with infrared lighting. Results: Significantly greater airflow occurred through the right nasal chamber (relative to the left) during periods of REM sleep than during periods of non-REM sleep (p<0.001). Both body position (p < 0.001) and sleep stage (p < 0.001) influenced nasal airflow lateralization. Conclusions: This study demonstrates that the lateralization of nasal airflow and sleep stage are related. Some types of asymmetrical somatosensory stimulation can alter this relationship.

RESUMO Objetivo: O ciclo nasal é um ritmo ultradiano de lado a lado de ingurgitamento associado com o ciclo da atividade autônoma. O objetivo deste estudo foi abordar a questão assim como a relação presente entre o ciclo nasal e os estágios de sono REM/não-REM. Também analisamos a confusão potencial da influência da posição corporal no fluxo de ar nasal. Métodos: Mensuramos o ciclo nasal em seis sujeitos durante um sono de oito horas usando um termistor nasal. Foi realizada uma polissonografia. Simultaneamente, nós monitoramos a posição corporal usando uma câmera de vídeo juntamente com luzes infravermelhas. Resultados: Um fluxo de ar maior ocorreu através da cavidade nasal direita durante as fases de sono REM do que nos períodos de sono não-REM (p < 0,001). Assim como a posição corporal [F(2.2340) = 86,99, p < 0,001] e o estágio de sono [F(1.2340) = 234.82, p < 0,001] influenciaram a lateralização do fluxo de ar nasal. Conclusões: Este estudo evidencia que a lateralização do fluxo de ar nasal e o estágio do sono estão relacionados. Alguns tipos de estimulação somatosensitiva assimétrica podem alterar esta relação.

Sensory aspects in myasthenia gravis: A translational approach.

Myasthenia gravis is a paradigmatic muscle disorder characterized by abnormal fatigue and muscle weakness that worsens with activities and improves with rest. Clinical and research studies done on nicotinic acetylcholine receptors have advanced our knowledge of the muscle involvement in myasthenia. Current views still state that sensory deficits are not "features of myasthenia gravis". This article discusses the gap that exists on sensory neural transmission in myasthenia that has remained after >300years of research in this neurological disorder. We outline the neurobiological characteristics of sensory and motor synapses, reinterpret the nanocholinergic commonalities that exist in both sensory and motor pathways, discuss the clinical findings on altered sensory pathways in myasthenia, and propose a novel way to score anomalies resulting from multineuronal inability associated sensory troubles due to eugenic nanocholinergic instability and autoimmunity. This medicine-based evidence could serve as a template to further identify novel targets for studying new medications that may offer a better therapeutic benefit in both sensory and motor dysfunction for patients. Importantly, this review may help to re-orient current practices in myasthenia.

Taste dysfunction in multiple sclerosis.

Empirical studies of taste function in multiple sclerosis (MS) are rare. Moreover, a detailed assessment of whether quantitative measures of taste function correlate with the punctate and patchy myelin-related lesions found throughout the CNS of MS patients has not been made. We administered a 96-trial test of sweet (sucrose), sour (citric acid), bitter (caffeine) and salty (NaCl) taste perception to the left and right anterior (CN VII) and posterior (CN IX) tongue regions of 73 MS patients and 73 matched controls. The number and volume of lesions were assessed using quantitative MRI in 52 brain regions of 63 of the MS patients. Taste identification scores were significantly lower in the MS patients for sucrose (p = 0.0002), citric acid (p = 0.0001), caffeine (p = 0.0372) and NaCl (p = 0.0004) and were present in both anterior and posterior tongue regions. The percent of MS patients with identification scores falling below the 5th percentile of controls was 15.07 % for caffeine, 21.9 % for citric acid, 24.66 % for sucrose, and 31.50 % for NaCl. Such scores were inversely correlated with lesion volumes in the temporal, medial frontal, and superior frontal lobes, and with the number of lesions in the left and right superior frontal lobes, right anterior cingulate gyrus, and left parietal operculum. Regardless of the subject group, women outperformed men on the taste measures. These findings indicate that a sizable number of MS patients exhibit taste deficits that are associated with MS-related lesions throughout the brain.

"Unclassical" Combination of Smell Dysfunction, Altered Abdominal Nociception and Human Hypertension Associated "Classical" Adrenal-Augmentation.

We report a 33-year-old female patient, who arrived to the emergency ward with an abdominal pain that suddenly started 10 days before admission. Simultaneously, the patient developed sudden arterial hypertension and smell disturbances. Conventional medical treatment for pain and arterial hypertension was effortless. Laboratory tests ruled out pancreatitis. Metanephrines in her urine were also normal. A dual-phase intravenous contrast computed tomography of the abdomen showed a large mass within left adrenal gland. Adrenocortical adenoma was diagnosed. The mass was not hypervascularized but positive for synaptophysin and chromogranin A. Importantly, these proteins are heavily involved with acetylcholine metabolism. The triad of olfactory disorders, pain and arterial hypertension normalized after surgically extracting the adrenal mass. To our knowledge, this medical case is the first reported patient exhibiting immediate recovery of such unclassical triad of local and remote findings. The function and dysfunction of key nanocholinergic pathways involved with smell, blood pressure and nociception would explain the pathophysiology of this unique medical case.

Auditory and Lower Limb Tactile Prepulse Inhibition in Primary Restless Legs Syndrome: Clues to Its Pathophysiology.

The resting sensory discomfort transiently relieved upon movement of the affected area in restless legs syndrome suggests that sensorimotor integration mechanisms, specifically gating, may be altered in the disease. The authors sought to determine the effects of prepulse auditory and tactile stimulation applied to lower limbs on the blink reflex of patients with restless legs syndrome and healthy subjects. Seventeen patients with restless legs syndrome and 17 age- and sex-matched healthy controls were investigated. Auditory stimuli and tactile lower limb stimulation were applied as prepulses. The R2 response of the blink reflex induced by electrical stimulation applied to the right supraorbital nerve was selected as the test stimulus. Time intervals between prepulses and response-eliciting stimuli were 40, 70, 90, 110, and 200 milliseconds. There were no differences in either the auditory or tactile prepulse conditions between patients and controls and no differences between these measures within subject groups. We concluded that the tactile lower limb and the auditory prepulse effects on the brainstem interneurons mediating the blink reflex share common neural pathways. Because forebrain interneurons mediate these prepulse effects, they are likely not involved in the disordered sensorimotor interaction of restless legs syndrome.

A new neurometric dissection of the area-under-curve-associated jiggle of the motor evoked potential induced by transcranial magnetic stimulation.

OBJECTIVE: The jiggle of the motor evoked potential (MEP) induced by transcranial magnetic stimulation (TMS) depends on a number of factors including the assessment of this stochastic signal by the method known as area under curve (AUC). We aim to ascertain the MEP findings assessed by the AUC method obtained from individuals affected by lesions at different levels of the neuroaxis. METHODS: We systematically search and critically appraise the scientific reports publishing on the MEP obtained from individuals with hypo- or hyperkinetic disorders of the neural system, and dissect the neurophysical assessment of the obtained data. To accomplish this, we used the instruments named to as U-Pen Instrument for Neurometric Evaluation Uncommonly and Rarely Obtained from NeuroSignals 1.0 (UPINEURON 1.0), and the Quality of Assessment Statistics Index (QuASI). RESULTS: The MEP differences found by the classical peak-to-peak method decreased or disappeared when the AUC was used. The opposite was also true (Kappa=<0.00). The internal consistency of the UPINEURON was 0.88. The mean of the UPINEURON 1.0 indicator was 34.8 (range=16-50), and the mean of the QuASI scores was 56.5 (range 30-80). Spearman correlation between UPINEURON 1.0 and QuASI was 0.513. CONCLUSIONS: The MEP jiggle found in individuals with disordered neural function is not a "minor" factor; it is beyond the underlying neural condition, sample size, type of coils, and number of trials, among other variables. The use of the novel indicators introduced in this investigation will help to improve the analysis of the AUC of neural signals. They may also lead to the reconsideration of current practices.