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.

Olfactory dysfunction in Parkinson's disease: Positive effect of cigarette smoking.

BACKGROUND: There is compelling evidence from over 60 epidemiological studies that smoking significantly reduces the risk of Parkinson's disease (PD). In general, those who currently smoke cigarettes, as well as those with a past history of such smoking, have a reduced risk of PD compared to those who have never smoked. Recently it has been suggested that a cardinal nonmotor sensory symptom of PD, olfactory dysfunction, may be less severe in PD patients who smoke than in PD patients who do not, in contrast to the negative effect of smoking on olfaction described in the general population. METHODS: We evaluated University of Pennsylvania Smell Identification Test (UPSIT) scores from 323 PD patients and 323 controls closely matched individually on age, sex, and smoking history (never, past, or current). RESULTS: Patients exhibited much lower UPSIT scores than did the controls (P < 0.0001). The relative decline in dysfunction of the current PD smokers was less than that of the never- and past-PD smokers (respective Ps = 0.0005 and 0.0019). Female PD patients outperformed their male counterparts by a larger margin than did the female controls (3.66 vs. 1.07 UPSIT points; respective Ps < 0.0001 and 0.06). Age-related declines in UPSIT scores were generally present (P < 0.0001). No association between the olfactory measure and smoking dose, as indexed by pack-years, was evident. CONCLUSIONS: PD patients who currently smoke do not exhibit the smoking-related decline in olfaction observed in non-PD control subjects who currently smoke. The physiological basis of this phenomenon is yet to be defined.

Suprathreshold odor intensity perception in early-stage Parkinson's disease.

BACKGROUND: Whether Parkinson's disease (PD) influences suprathreshold changes in perceived odor intensity is unknown. In patients with Alzheimer's disease, patients with schizophrenia, and the elderly, such perception is reportedly normal. If generally true, this could reflect a core element of the olfactory system insulated to some degree from age- and disease-related pathological conditions. METHODS: Odor intensity ratings for pentyl acetate were obtained from 29 early-stage PD patients when on and off dopamine-related medications (DRMs) and from 29 matched controls. RESULTS: The ratings were significantly attenuated at the higher odorant concentrations, with the degree of attenuation associated with overall olfactory dysfunction. Ratings were higher on the right than on the left side of the nose of both patients and controls. No associations with DRMs, Unified Parkinson's Disease Rating Scale (UPDRS) scores, or striatal dopamine transporter imaging were found. CONCLUSIONS: Parkinson's disease (PD) influences suprathreshold estimates of perceived odor intensity, negating the notion that such perception might be spared in this disease. No association with dopaminergic processes was apparent.

Nature and nurture in stuttering: a systematic review on the case of Moses.

Stuttering is a disturbance of normal fluency of speech whose pathophysiology is still not well understood. We investigated one of the most ancient speech disorders in the biblical person Moses who lived in approximately 1300 BC. To get the most complete medical and non-medical information on Moses, we did systematic searches in the Holy Bible using the Bible-Discovery v2.3© software ( http://www.bible-discovery.com ) looking for verses containing the terms "Moses", "Stuttering" and "Stutter"; and in PubMed/Medline database for manuscripts having the terms "Moses", "Bible" and "Stuttering". From the Bible search, 742 verses were found, of which 23 were relevant; three additional verses were found by hand search. Six papers discussing Moses's pathology were found in the PubMed search. The analysis of ancient descriptions in the light of current research suggests that stuttering is the most likely pathology Moses had, with clear evidence for both genetic origin and environmental triggers. Further, it was found that Moses practiced some "sensory tricks" that could be used to relieve his speech disorder which are, to our knowledge, the first "tricks" that successfully modulated a movement disorder described in the medical literature.

Primary and Reversible Pisa Syndrome in Juvenile Normal Pressure Hydrocephalus.

OBJECTIVE: To report a case of Pisa syndrome in a patient with idiopathic normal pressure hydrocephalus, who had never been exposed to psychotropic medications. METHODS: A 26 years-old, Colombian, male patient, was referred because he had cognitive abnormalities, gait disturbances and urinary incontinence. This patient also displayed pleurothotonos. Neurofunctional evaluation of sensory and motor integration at peripheral and central nervous system levels were done. RESULTS: Pisa syndrome disappeared after spinal tap drainage with further gait, balance and behavioral improvement. A brainstem-thalamocortical deregulation of the central sensory and motor programming, due to the chaotic enlargement of brain ventricles was thought to be the pathophysiological mechanism underlying this case. CONCLUSION: NPH must not be longer considered as an exclusive geriatric disorder. Further, uncommon movement disorders may appear with this disorder, which should be carefully approached to avoid iatrogenic and deleterious pharmacological interventions.

[Present and future of the transcranial magnetic stimulation]. / Presente y futuro de la estimulación magnética transcraneal.

Magnetic stimulation has called the attention of neuroscientists and the public due to the possibility to stimulate and "control" the nervous system in a non-invasive way. It has helped to make more accurate diagnosis, and apply more effective treatments and rehabilitation protocols in several diseases that affect the nervous system. Likewise, this novel tool has increased our knowledge about complex neural behavior, its connections as well as its plastic modulation. Magnetic stimulation applied in simple or paired-pulse protocols is a useful alternative in the diagnosis of diseases such as multiple sclerosis, Parkinson disease, epilepsy, dystonia, amyotrophic lateral sclerosis, cerebrovascular disease, and sleep disorders. From the therapeutic perspective, magnetic stimulation applied repetitively has been found useful, with different degrees of efficacy, in treating resistant depression, tinnitus, psychogenic dysphonia, Alzheimer disease, autism, Parkinson disease, dystonia, stroke, epilepsy, generalized anxiety as well as post traumatic stress disorder, auditory hallucinations, chronic pain, aphasias, obsessive-compulsive disorders, L-dopa induced dyskynesia, mania and Rasmussen syndrome, among others. The potential of magnetic stimulation in neurorehabilitation is outstanding, with excellent range of safety and, in practical terms, without side effects.

[Neurorehabilitation: from a rigid past to a plastic future]. / Neurorrehabilitación: de un pasado rígido a un futuro plástico.

Since ancient times, several cultures including those from China, Egypt, India and Rome gave rigid solutions to improve physical problems of affected people by several neurological disorders. These measures were applied, at that time, by individuals prepared for doing such task. It evolved throughout the years supported by the discovery and comprehension of the so-called neural plasticity as well as the current evidences that the nervous system is able of remodelating itself even in adult times. It is known today that synaptic modulation is the base of neurorehabilitation improved by use and application of specific protocols to each neurological disorder. Among these, we have to consider not only all of the already known on rehabilitation measures but also on neurorobotic, neurorestauration, neuromodulation, neurostimulation as well as virtual reality, among others interventions. Neurorehabilitation has been able to put together modern science with ancient manual therapies helping to change, in a positive way, the attitude toward people with disabilities in the twenty one century; likewise, it offers new hopes for functional recovery where before was nothing. Further, it gives opportunities to get a better quality of life to affected people and its corresponding families. It is very interesting to know that the modern concepts of neurorehabilitation performed in a multidisciplinary approach are very useful for humans on the Earth and people interested in conquer Space.

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.

[Magnetoreception: the angular stone in aerospace orientation, human balance and locomotion]. / Magnetorrecepción: la piedra angular de la orientación aeroespacial, balance y locomoción humana.

Current research is in agreement with the presence of a magnetic compass in living beings including humans. The two most accepted explanations that demonstrate the existence of magnetoreceptors in living beings are, the radical pair and the biogenic magnetite, which are discussed here with its respective experimental evidence and support. It indicates the presence of magnetite crystals in otoliths, among different inferior species of animals. Moreover, the magnetite found in several organs of human body allows predicting the existence of such element, in otoliths of vestibular system as well; further, anticipates that human magnetoreception is an additional function of the vestibular system. These geomagnetic signals would modulate balance, movement and spatial positioning of man in concordance of gravity values. This new field of otomagnetism opens new research areas for understanding the mechanisms involved in balance, equilibrium, orientation, and space positioning in normal and disease populations. Likewise, this could be the starting point for application of new human neurorehabilitation procedures, in those magnetoreception-associated neurological disorders that happen in the earth, the sea or the air.

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.

Incomplete facial nerve palsy: new lessons from activated orbicularis oculi muscles.

Motor nerve conduction studies (MNCS) and blink reflexes (BR) were done on a 42-year-old female patient who presented with peripheral facial nerve palsy (PFNP); these investigations were done while she had her facial muscles relaxed ("A"), and contracted ("B"). While in the "A" state, MNCS of the facial nerves had prolonged latency and low amplitude and R3 of the blink reflex was absent in the affected side; an early contralateral R1 response was recorded on the unaffected side. In state "B," the third silent period was "prolonged" on the affected side and absent on the unaffected one. This is an illustrative case of a variant of facial nerve palsy in humans.

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.

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.

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.

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.

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.

Abnormal tactile discrimination and somatosensory plasticity in familial primary hyperhidrosis.

Abnormal sensory processing seems to be involved in hyperhidrosis. To test this hypothesis, we investigated tactile acuity and cortical plastic changes in patients with primary hyperhidrosis (PH) and their asymptomatic relatives. We studied thirteen subjects belonging to two families with PH and thirteen age-matched healthy controls using Johnson-Van Boven-Phillips domes before and after 45min of transient visual deafferentation. Spatial discrimination thresholds (SDTs) were lower in controls than in the familial group (1.08+/-0.25 vs 1.59+/-0.71; p=0.0032). After 45min of light deprivation and blindfolding, SDTs decreased significantly in controls (0.83+/-0.3; p=0.003), but not in patients (1.4+/-0.62; p=0.108). Interestingly, two subjects without clinical complaints of hyperhidrosis had abnormal SDTs behavior after short term visual deprivation. This study demonstrates that sensory processing is abnormal in PH, with a lack of plastic cortical somatosensory changes regardless of clinical condition. These modulatory abnormalities would affect gating processes in the somatosensory cortex which may play a role in maintaining hyperhidrosis.

[Functional neurology of blepharospasm]. / Neurología funcional del blefaroespasmo.

Benign essential blepharospasm is characterized by abnormal repetitive movements of lid closure and spasm of the orbiculari oculi muscles. Modern theories postulate that this movement disorder originates by abnormal processing of afferent information with further disintegration of the sensorimotor neural program at central levels of the nervous system all of which is seen as dystonic movements in genetically susceptible people. Different investigations including neuroimagin, genetic and neurophysiological studies have discovered new findings on what structures are involved and how this abnormal movement is generated. Among these research is noteworthy the study of electrically elicited blink reflex. It consists of three responses called non-nociceptive (R1), nociceptive (R2) and ultranociceptive (R3). Such blink reflexes, mostly the ultranociceptive response (R3), seem to be very useful to understand more deeply the pathophysiology of this focal dystonia, to perform the functional endophenotyping and to do a more appropriate follow-up of this complex neurological problem.

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.