Advancing Intraoperative Neurophysiological Monitoring With Human Reflexes.

Human reflexes are simple motor responses that are automatically elicited by various sensory inputs. These reflexes can provide valuable insights into the functioning of the nervous system, particularly the brainstem and spinal cord. Reflexes involving the brainstem, such as the blink reflex, laryngeal adductor reflex, trigeminal hypoglossal reflex, and masseter H reflex, offer immediate information about the cranial-nerve functionality and the overall state of the brainstem. Similarly, spinal reflexes such as the H reflex of the soleus muscle, posterior root muscle reflexes, and sacral reflexes provide crucial information about the functionality of the spinal cord and peripheral nerves. One of the critical benefits of reflex monitoring is that it can provide continuous feedback without disrupting the surgical process due to no movement being induced in the surgical field. These reflexes can be monitored in real time during surgical procedures to assess the integrity of the nervous system and detect potential neurological damage. It is particularly noteworthy that the reflexes provide motor and sensory information on the functional integrity of nerve fibers and nuclei. This article describes the current techniques used for monitoring various human reflexes and their clinical significance in surgery. We also address important methodological considerations and their impact on surgical safety and patient outcomes. Utilizing these methodologies has the potential to advance or even revolutionize the field of intraoperative continuous monitoring, ultimately leading to improved surgical outcomes and enhanced patient care.

The blink reflex and its modulation - Part 1: Physiological mechanisms.

The blink reflex (BR) is a protective eye-closure reflex mediated by brainstem circuits. The BR is usually evoked by electrical supraorbital nerve stimulation but can be elicited by a variety of sensory modalities. It has a long history in clinical neurophysiology practice. Less is known, however, about the many ways to modulate the BR. Various neurophysiological techniques can be applied to examine different aspects of afferent and efferent BR modulation. In this line, classical conditioning, prepulse and paired-pulse stimulation, and BR elicitation by self-stimulation may serve to investigate various aspects of brainstem connectivity. The BR may be used as a tool to quantify top-down modulation based on implicit assessment of the value of blinking in a given situation, e.g., depending on changes in stimulus location and probability of occurrence. Understanding the role of non-nociceptive and nociceptive fibers in eliciting a BR is important to get insight into the underlying neural circuitry. Finally, the use of BRs and other brainstem reflexes under general anesthesia may help to advance our knowledge of the brainstem in areas not amenable in awake intact humans. This review summarizes talks held by the Brainstem Special Interest Group of the International Federation of Clinical Neurophysiology at the International Congress of Clinical Neurophysiology 2022 in Geneva, Switzerland, and provides a state-of-the-art overview of the physiology of BR modulation. Understanding the principles of BR modulation is fundamental for a valid and thoughtful clinical application (reviewed in part 2) (Gunduz et al., submitted).

Unexpected median SEPs fluctuations during brain cavernous malformation resection with no post-operative deficit.

Median nerve somatosensory evoked potentials (SEPs) may present changes during cavernous malformation (CM) resection unrelated to new post-operative sensory deficits. We performed intraoperative neurophysiological monitoring of median SEPs (m-SEPs) in three patients who underwent CM resection (surgery) near the sensory-motor cortex. The only preoperative clinical manifestations in all patients were seizures. All patients presented m-SEPs alterations on the side of the lesion during the procedure. Two patients presented permanent changes in the cortical potentials. In the third patient, the cortical and subcortical components suffered temporal fluctuations to return to baselines at the end of the surgery. None of these patients developed new post-operative clinical deficits. During brain cavernous malformation resection, significant fluctuations in the amplitude of different components of m-SEPs may occur. These changes may be due to excitability variations on m-SEP generators and do not translate into new post-operative neurological deficits.

Median nerve somatosensory evoked potential alarm related to head and neck positioning for carotid surgery.

Head positioning in carotid surgery represents an often overlooked but sensitive period in the surgical plan. A 53-year-old male presented a significant decrement in median nerve somatosensory evoked potential (mSEP) following head and neck positioning for carotid pseudoaneurysm repair before skin incision.Neurophysiological monitoring was performed with mSEP and electroencephalography early during the patient's preparation and surgery. Within five minutes after rotation and extension of the head to properly expose the surgical field, the contralateral m-SEP significantly decreased in both cortical (N20/P25) and subcortical (P14/N18) components. Partial neck correction led to m-SEP improvement, allowing to proceed with the carotid repair. We discuss possible underlying pathophysiological mechanisms responsible for these changes and highlight the relevance of an early start on monitoring to avoid neurological deficits.

Continuous intraoperative neuromonitoring of the recurrent laryngeal nerve by eliciting the laryngeal adductor reflex (LAR-CIONM).

The laryngeal adductor reflex (LAR) is a life-sustaining airway protective mechanism that serves to shield the lower airways from inhaled foreign bodies. Over the past half century, the LAR has been extensively investigated and its dysfunction has been linked to far-ranging pathologies, from dysphagia to sudden infant death syndrome. Over the past 6 years, specific electromyographic waves in the LAR response have been used to devise a methodology for monitoring the vagus and recurrently laryngeal nerves during surgical procedures. This methodology involves continuous intraoperative neuromonitoring of the laryngeal adductor reflex and isthus termed 'LAR-CIONM'. In this review paper, the physiology of the LAR will be summarized as it relates to LAR-CIONM and the technique of LAR-CIONM will be described. Applications of this technique and published outcomes of LAR-CIONM will be highlighted.

No evidence of brown adipose tissue activation after 24 weeks of supervised exercise training in young sedentary adults in the ACTIBATE randomized controlled trial.

Exercise modulates both brown adipose tissue (BAT) metabolism and white adipose tissue (WAT) browning in murine models. Whether this is true in humans, however, has remained unknown. An unblinded randomized controlled trial (ClinicalTrials.gov ID: NCT02365129) was therefore conducted to study the effects of a 24-week supervised exercise intervention, combining endurance and resistance training, on BAT volume and activity (primary outcome). The study was carried out in the Sport and Health University Research Institute and the Virgen de las Nieves University Hospital of the University of Granada (Spain). One hundred and forty-five young sedentary adults were assigned to either (i) a control group (no exercise, n = 54), (ii) a moderate intensity exercise group (MOD-EX, n = 48), or (iii) a vigorous intensity exercise group (VIG-EX n = 43) by unrestricted randomization. No relevant adverse events were recorded. 97 participants (34 men, 63 women) were included in the final analysis (Control; n = 35, MOD-EX; n = 31, and VIG-EX; n = 31). We observed no changes in BAT volume (Δ Control: -22.2 ± 52.6 ml; Δ MOD-EX: -15.5 ± 62.1 ml, Δ VIG-EX: -6.8 ± 66.4 ml; P = 0.771) or 18F-fluorodeoxyglucose uptake (SUVpeak Δ Control: -2.6 ± 3.1 ml; Δ MOD-EX: -1.2 ± 4.8, Δ VIG-EX: -2.2 ± 5.1; p = 0.476) in either the control or the exercise groups. Thus, we did not find any evidence of an exercise-induced change on BAT volume or activity in young sedentary adults.

Methodology for eliciting the brainstem trigeminal-hypoglossal reflex in humans under general anesthesia.

OBJECTIVE: Brainstem trigeminal-hypoglossal reflexes (THRs), also known as the jaw-tongue reflexes, coordinate the position of the tongue in the mouth in relation to the jaw movement during oromotor behaviors such as mastication, swallowing, vocalization, and breathing. Their use in brainstem surgery however, has never been assessed in spite of its potential benefit possibly due to the lack of a methodology to elicit these reflexes under general anesthesia. METHODS: We proposed a technique to elicit the THRs during total intravenous anesthesia (TIVA) consisting on a V3 infrazygomatic train stimulation paradigm and recording from the Styloglossus (31 patients) and the Genioglossus (21 patients) muscles to elicit long latency responses. RESULTS: The THR was successfully recorded using the V3 stimulation point in 82.1% of patients, of which 96.9% presented a response on the Styloglossus muscle (Jaw-opening reflex) while 0.06% presented a response on the Genioglossus muscle instead (Jaw-closing reflex). CONCLUSIONS: The THRs can be successfully recorded in surgery under general anaesthesia with the predominant reflex seen being the jaw-opening reflex. SIGNIFICANCE: We provide a novel method to elicit the THRs during general anesthesia, which could be of aid in brainstem surgery.

Epidemiological trends of HIV/HCV coinfection in Spain, 2015-2019.

OBJECTIVES: We assessed the prevalence of anti-hepatitis C virus (HCV) antibodies and active HCV infection (HCV-RNA-positive) in people living with HIV (PLWH) in Spain in 2019 and compared the results with those of four similar studies performed during 2015-2018. METHODS: The study was performed in 41 centres. Sample size was estimated for an accuracy of 1%. Patients were selected by random sampling with proportional allocation. RESULTS: The reference population comprised 41 973 PLWH, and the sample size was 1325. HCV serostatus was known in 1316 PLWH (99.3%), of whom 376 (28.6%) were HCV antibody (Ab)-positive (78.7% were prior injection drug users); 29 were HCV-RNA-positive (2.2%). Of the 29 HCV-RNA-positive PLWH, infection was chronic in 24, it was acute/recent in one, and it was of unknown duration in four. Cirrhosis was present in 71 (5.4%) PLWH overall, three (10.3%) HCV-RNA-positive patients and 68 (23.4%) of those who cleared HCV after anti-HCV therapy (p = 0.04). The prevalence of anti-HCV antibodies decreased steadily from 37.7% in 2015 to 28.6% in 2019 (p < 0.001); the prevalence of active HCV infection decreased from 22.1% in 2015 to 2.2% in 2019 (p < 0.001). Uptake of anti-HCV treatment increased from 53.9% in 2015 to 95.0% in 2019 (p < 0.001). CONCLUSIONS: In Spain, the prevalence of active HCV infection among PLWH at the end of 2019 was 2.2%, i.e. 90.0% lower than in 2015. Increased exposure to DAAs was probably the main reason for this sharp reduction. Despite the high coverage of treatment with direct-acting antiviral agents, HCV-related cirrhosis remains significant in this population.

Clarifying optimal outcome measures in intermittent and continuous laryngeal neuromonitoring.

BACKGROUND: Intraoperative neuromonitoring (IONM) techniques have evolved over the past decade into intermittent IONM (I-IONM) and continuous IONM (C-IONM) modes of application. Despite many prior publications on both types of IONM, there remains uncertainty about what outcomes should be measured for each form of IONM. The primary objective of this paper is to define categories of benefit for I-IONM/C-IONM and to clarify and standardize their reporting outcomes. METHODS: Expert review consensus statement utilizing modified Delphi methodology. RESULTS: I-IONM provides diagnosis, classification, and prevention of nerve injury through accurate and early nerve identification. C-IONM provides real-time information on nerve functional integrity and thus may prevent some types of nerve injury but cannot assist in nerve localization. Sudden mechanisms of nerve injury cannot be predicted or prevented by either technique. CONCLUSIONS: I-IONM and C-IONM are complementary techniques. Future studies evaluating the utility of IONM should focus on outcomes that are appropriate to the type of IONM being utilized.

Optimizing the methodology for saphenous nerve somatosensory evoked potentials for monitoring upper lumbar roots and femoral nerve during lumbar spine surgery: technical note.

The demand for intraoperative monitoring (IOM) of lumbar spine surgeries has escalated to accommodate more challenging surgical approaches to prevent perioperative neurologic deficits. Identifying impending injury of individual lumbar roots can be done by assessing free-running EMG and by monitoring the integrity of sensory and motor fibers within the roots by eliciting somatosensory (SEP), and motor evoked potentials. However, the common nerves for eliciting lower limb SEP do not monitor the entire lumbar plexus, excluding fibers from L1 to L4 roots. We aimed to technically optimize the methodology for saphenous nerve SEP (Sap-SEP) proposed for monitoring upper lumbar roots in the operating room. In the first group, the saphenous nerve was consecutively stimulated in two different locations: proximal in the thigh and distal close to the tibia. In the second group, three different recording derivations (10-20 International system) to distal saphenous stimulation were tested. Distal stimulation yielded a higher Sap-SEP amplitude (mean ± SD) than proximal: 1.36 ± 0.9 µV versus 0.62 ± 0.6 µV, (p < 0.0001). Distal stimulation evoked either higher (73%) or similar (12%) Sap-SEP amplitude compared to proximal in most of the nerves. The recording derivation CPz-cCP showed the highest amplitude in 65% of the nerves, followed by CPz-Fz (24%). Distal stimulation for Sap-SEP has advantages over proximal stimulation, including simplicity, lack of movement and higher amplitude responses. The use of two derivations (CPz-cCP, CPz-Fz) optimizes Sap-SEP recording.

The short-latency R1 response of the electrical laryngeal adductor reflex contributes to airway protection by initiating glottic closure.

OBJECTIVE: The fundamental role of the short-latency (R1) laryngeal adductor reflex (LAR) response remains unclear with conflicting reports in the literature. This study's primary aim was to objectively determine whether the bilateral R1 response, which was elicited by electrical stimulation of the supraglottic mucosa, triggered bilateral glottis closure. METHODS: Video recording of the LAR in a prospective case series of patients undergoing trans-oral rigid laryngoscopy. The LAR was elicited by electrical stimulation of supraglottic mucosa. The LAR R1 and long-latency (R2) responses in laryngeal adductor musculature were correlated with mechanical vocal fold (VF) adduction in a time-locked manner. A high-speed camera recording 1057 frames per second was used to determine where in the LAR contractile closure the electrical R1 component occurred. RESULTS: Five patients were prospectively enrolled. The R1 response was present in all trials for all patients. The R2 response was recorded in four patients (80%). As assessed by the latency of the R1 response, electrical activation of the adductor muscles always preceded the mechanical onset of VF movement. VF adduction began near the middle of the R1 response in all trials for all patients. The R2 response of the LAR began after visible VF adduction for all patients. CONCLUSIONS: This study provides the first objective evidence that the bilateral R1 response of the electrically elicited LAR is the electrical event that initiates reflex airway closure. SIGNIFICANCE: These results suggest that under total intravenous anesthesia, the larynx preserves its capacity to elicit a LAR, thereby maintaining some protective functions that can prevent airway penetration.

Quadriplegia, an Unusual Outcome After Anterior Cervical Discectomy and Fusion: A Case Report.

CASE: A 68-year-old woman who underwent a C5 to C6 anterior cervical discectomy and fusion (ACDF) surgery presented with new-onset postoperative quadriplegia. During discectomy, intraoperative neurophysiological monitoring alerted of a spinal cord (SC) dysfunction. The surgery was halted, and measures to ensure adequate SC perfusion were initiated. In the next 2-week follow-up, patient's motor deficit progressively improved. CONCLUSIONS: We report an unusual and devastating outcome of new-onset quadriplegia after an elective ACDF and highlight the relevance of intraoperative monitoring during cervical spine surgery to early recognize and treat SC impending injury.

Relationship between dietary factors and S-Klotho plasma levels in young sedentary healthy adults.

OBJECTIVE: To study the associations of dietary factors with S-Klotho plasma levels in young adults. We also aimed to study whether body composition and cardiometabolic risk factors affected the association between dietary factors and S-Klotho plasma levels. METHODS: A total of 139 young adults took part in this study. Dietary factors were measured using a food frequency questionnaire and three non-consecutive 24 h recalls. S-Klotho plasma levels were measured by immunosorbent assay. Body composition was measured by DXA. RESULTS: We observed a direct association of ethanol intake and S-Klotho plasma levels in women. An inverse association was also observed between the dietary inflammatory index (DII) with S-Klotho plasma levels in all sample. No mediation effects of body composition or cardiometabolic risk factors were observed in the relationship between alcohol and S-Klotho plasma levels. Lean mass index (LMI) and uric acid levels mediated the relationship between DII and S-Klotho plasma levels. CONCLUSION: A pro-inflammatory dietary pattern was inversely associated with S-Klotho plasma levels in young adults, which was partially mediated by LMI and uric acid levels.

Continuous neuromonitoring during radiofrequency ablation of benign thyroid nodules provides objective evidence of laryngeal nerve safety.

INTRODUCTION: The recurrent laryngeal nerves(RLN) run immediately posterior to the thyroid capsule and could be injured during thyroid radiofrequency ablation(RFA). This study assesses whether RLN functional integrity is altered during RFA using continuous intraoperative neuromonitoring(CIONM). METHODS: Prospective case series of twenty nodules treated with RFA under general anesthesia utilizing the laryngeal adductor reflex(LAR) for CIONM. RESULTS: Thirteen nodules abutted the posterior thyroid capsule and 'danger triangle' for RLN injury. The ablative field did not breach the posterior capsule; 40 W was the maximal power used adjacent to the capsule. No patient experienced significant LAR amplitude alterations. Pre and postoperative laryngoscopy and voice assessments were comparable. At 12 months' median follow-up, no patient displayed posterior nodule regrowth. CONCLUSIONS: This prospective case series supports the premise that benign nodule RFA is safe with regards to RLN functional integrity provided the posterior capsule is not breached by the ablation zone and posterior power is ≤ 40 W.

Mortality risk assessment in Spain and Italy, insights of the HOPE COVID-19 registry.

Recently the coronavirus disease (COVID-19) outbreak has been declared a pandemic. Despite its aggressive extension and significant morbidity and mortality, risk factors are poorly characterized outside China. We designed a registry, HOPE COVID-19 (NCT04334291), assessing data of 1021 patients discharged (dead or alive) after COVID-19, from 23 hospitals in 4 countries, between 8 February and 1 April. The primary end-point was all-cause mortality aiming to produce a mortality risk score calculator. The median age was 68 years (IQR 52-79), and 59.5% were male. Most frequent comorbidities were hypertension (46.8%) and dyslipidemia (35.8%). A relevant heart or lung disease were depicted in 20%. And renal, neurological, or oncological disease, respectively, were detected in nearly 10%. Most common symptoms were fever, cough, and dyspnea at admission. 311 patients died and 710 were discharged alive. In the death-multivariate analysis, raised as most relevant: age, hypertension, obesity, renal insufficiency, any immunosuppressive disease, 02 saturation < 92% and an elevated C reactive protein (AUC = 0.87; Hosmer-Lemeshow test, p > 0.999; bootstrap-optimist: 0.0018). We provide a simple clinical score to estimate probability of death, dividing patients in four grades (I-IV) of increasing probability. Hydroxychloroquine (79.2%) and antivirals (67.6%) were the specific drugs most commonly used. After a propensity score adjustment, the results suggested a slight improvement in mortality rates (adjusted-ORhydroxychloroquine 0.88; 95% CI 0.81-0.91, p = 0.005; adjusted-ORantiviral 0.94; 95% CI 0.87-1.01; p = 0.115). COVID-19 produces important mortality, mostly in patients with comorbidities with respiratory symptoms. Hydroxychloroquine could be associated with survival benefit, but this data need to be confirmed with further trials. Trial Registration: NCT04334291/EUPAS34399.

Intraoperative Neurophysiologic Monitoring Correlates with Neurologic Outcome After Endovascular and Surgical Treatment of a Cervical Arteriovenous Malformation.

BACKGROUND: The treatment of spinal intramedullary arteriovenous malformations (AVMs) presents the risk of spinal cord ischemia because of the vascular nidus and their feeding arteries involving and supplying the spinal cord parenchyma. The multimodal approach includes endovascular embolization and microsurgical excision, both benefiting from intraoperative neurophysiologic monitoring. We present a case study of a patient who underwent several staged embolizations and open surgery for microsurgical excision. PATIENT: A 32-year-old man who presented with a recurrent glomus-type intramedullary AVM in the cervical spinal cord, located at the C5-C6 segment, with progressive neurologic deterioration. METHODS: Somatosensory evoked potentials (SEPs) and transcranial motor evoked potentials (MEPs) were performed during three embolizations, a provocative test, and surgery, in addition to D-wave during microsurgical excision. RESULTS: Abolished hand MEP and drop in SEP during a provocative test guided the surgeon to embolize from a safer vessel with no acute neurologic deficit after three embolizations. Before surgery, an angiography showed the left posterior spinal artery supplying the AVM. After resecting the vascular nidus from the spinal parenchyma, left-hand MEP decreased in amplitude and later abolished, and SEP decreased. Interestingly, no D-wave or distal MEPs were affected. Weakness in the left hand immediately and 2 weeks postoperatively advocates for metameric spinal cord ischemia with preservation of long spinal cord pathways. CONCLUSIONS: Intraoperative neurophysiologic monitoring correlates with neurologic outcome after endovascular and surgical treatment of a cervical AVM. Intraoperative monitoring provides continuous functional information of long and metameric spinal cord pathways, which is critical when deciding on the vessel to be embolized and during microsurgical excision where the surgeon is in less control of the AVM hemodynamic flow.