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.

Cortico-cortical evoked potentials of language tracts in minimally invasive glioma surgery guided by Penfield stimulation.

OBJECTIVE: We investigated the feasibility of recording cortico-cortical evoked potentials (CCEPs) in patients with low- and high-grade glioma. We compared CCEPs during awake and asleep surgery, as well as those stimulated from the functional Broca area and recorded from the functional Wernicke area (BtW), and vice versa (WtB). We also analyzed CCEP properties according to tumor location, histopathology, and aphasia. METHODS: We included 20 patients who underwent minimally invasive surgery in an asleep-awake-asleep setting. Strip electrode placement was guided by classical Penfield stimulation of positive language sites and fiber tracking of the arcuate fascicle. CCEPs were elicited with alternating monophasic single pulses of 1.1 Hz frequency and recorded as averaged signals. Intraoperatively, there was no post-processing of the signal. RESULTS: Ninety-seven CCEPs from 19 patients were analyzed. There was no significant difference in CCEP properties when comparing awake versus asleep, nor BtW versus WtB. CCEP amplitude and latency were affected by tumor location and histopathology. CCEP features after tumor resection correlated with short- and long-term postoperative aphasia. CONCLUSION: CCEP recordings are feasible during minimally invasive surgery. CCEPs might be surrogate markers for altered connectivity of the language tracts. SIGNIFICANCE: This study may guide the incorporation of CCEPs into intraoperative neurophysiological monitoring.

Intraoperative Neurophysiologic Monitoring and Mapping in Children Undergoing Brainstem Surgery.

SUMMARY: Intraoperative neurophysiologic monitoring during surgery for brainstem lesions is a challenge for intraoperative neurophysiologists and surgeons. The brainstem is a small structure packed with vital neuroanatomic networks of long and short pathways passing through the brainstem or originating from it. Many central pattern generators exist within the brainstem for breathing, swallowing, chewing, cardiovascular regulation, and eye movement. During surgery around the brainstem, these generators need to be preserved to maintain their function postoperatively. This short review presents neurophysiologic and neurosurgical experiences of brainstem surgery in children.

Intraoperative Neurophysiologic Monitoring and Mapping During Surgery on Intramedullary Spinal Cord Tumors in Children and Adolescents.

SUMMARY: Surgical resection of intramedullary spinal cord tumors carries significant risks of neurologic deficits, especially in cases of infiltrative tumors. In pediatric patients, this type of surgery may be associated with a high risk of poor neurologic outcome. Intraoperative neurophysiologic monitoring has been adopted as part of the clinical routine by many centers as a useful adjunct for intraoperative assessment of neurologic integrity. To what extent intraoperative neurophysiologic mapping strategies may further support intraoperative decision-making is still a matter of debate. Here, we report on a small cohort of five pediatric patients in whom mapping with the double-train paradigm was used to identify the dorsal column and corticospinal tract and to guide the surgical resection. We also discuss the possible benefits and challenges regarding the available literature.

Deep brain stimulation in disorders of consciousness: 10 years of a single center experience.

Disorders of consciousness (DoC), namely unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS), represent severe conditions with significant consequences for patients and their families. Several studies have reported the regaining of consciousness in such patients using deep brain stimulation (DBS) of subcortical structures or brainstem nuclei. Our study aims to present the 10 years' experience of a single center using DBS as a therapy on a cohort of patients with DoC. Eighty Three consecutive patients were evaluated between 2011 and 2022; entry criteria consisted of neurophysiological and neurological evaluations and neuroimaging examinations. Out of 83, 36 patients were considered candidates for DBS implantation, and 32 patients were implanted: 27 patients had UWS, and five had MCS. The stimulation target was the centromedian-parafascicular complex in the left hemisphere in hypoxic brain lesion or the one better preserved in patients with traumatic brain injury. The level of consciousness was improved in seven patients. Three out of five MCS patients emerged to full awareness, with the ability to interact and communicate. Two of them can live largely independently. Four out of 27 UWS patients showed consciousness improvement with two patients emerging to full awareness, and the other two reaching MCS. In patients with DoC lasting longer than 12 months following traumatic brain injury or 6 months following anoxic-ischemic brain lesion, spontaneous recovery is rare. Thus, DBS of certain thalamic nuclei could be recommended as a treatment option for patients who meet neurological, neurophysiological and neuroimaging criteria, especially in earlier phases, before occurrence of irreversible musculoskeletal changes. Furthermore, we emphasize the importance of cooperation between centers worldwide in studies on the potentials of DBS in treating patients with DoC.

Brainstem Surgery: Functional Surgical Anatomy with the Use of an Advanced Modern Intraoperative Neurophysiological Procedure.

Intraoperative neurophysiology (ION) in brainstem surgery evolved as brainstem surgery advanced.The original idea of brainstem mapping (BSM) is a neurophysiological procedure to locate cranial nerve motor nuclei (CNMN) on the floor of the fourth ventricle. With the introduction of various skull base approaches to the brainstem, BSM is carried out on any surface of the brainstem to expose the safe entry zone to the intrinsic brainstem lesion. It is the modern concept of BSM, a broader definition of BSM. BSM enables to avoid direct damage to the CNMN when approaching the brainstem through the negative mapping region.The corticobulbar tract (CBT) motor evoked potential (MEP) is another ION procedure in brainstem surgery. It enables monitoring of the functional integrity of the whole cranial motor pathway without interrupting surgical procedures. Combined application of both BSM and CBT-MEP monitoring is indispensable for the functional preservation of the CNMN and their supranuclear innervation during the brainstem surgery.In this paper, the neurophysiological aspect of BSM and the CBT-MEP was fully described. Normal anatomical background of the floor of the fourth ventricle and the detail of the CBT anatomy were demonstrated to better understand their clinical usefulness, limitations, and surgical implications derived from ION procedures. Finally, a future perspective in the role of ION procedures in brainstem surgery was presented. The latest magnetic resonance imaging (MRI) technology can allow surgeons to find an "on the image" safe entry zone to the brainstem. However, the role of BSM and the CBT-MEP monitoring in terms of safe brainstem surgery stays unshakable. Special attention was paid for the recent trend of management in diffuse intrinsic pontine gliomas. A new role of BSM during a stereotactic biopsy was discussed.It is the authors' expectation that the paper enhances the clinical application of a contemporary standard of the ION in brainstem surgery and supports safer brainstem surgery more than ever and in the future.

Dysfunctional connectivity as a neurophysiologic mechanism of disorders of consciousness: a systematic review.

Introduction: Disorders of consciousness (DOC) has been an object of numbers of research regarding the diagnosis, treatment and prognosis in last few decades. We believe that the DOC could be considered as a disconnection syndrome, although the exact mechanisms are not entirely understood. Moreover, different conceptual frameworks highly influence results interpretation. The aim of this systematic review is to assess the current knowledge regarding neurophysiological mechanisms of DOC and to establish possible influence on future clinical implications and usage. Methods: We have conducted a systematic review according to PRISMA guidelines through PubMed and Cochrane databases, with studies being selected for inclusion via a set inclusion and exclusion criteria. Results: Eighty-nine studies were included in this systematic review according to the selected criteria. This includes case studies, randomized controlled trials, controlled clinical trials, and observational studies with no control arms. The total number of DOC patients encompassed in the studies cited in this review is 1,533. Conclusion: Connectomics and network neuroscience offer quantitative frameworks for analysing dynamic brain connectivity. Functional MRI studies show evidence of abnormal connectivity patterns and whole-brain topological reorganization, primarily affecting sensory-related resting state networks (RSNs), confirmed by EEG studies. As previously described, DOC patients are identified by diminished global information processing, i.e., network integration and increased local information processing, i.e., network segregation. Further studies using effective connectivity measurement tools instead of functional connectivity as well as the standardization of the study process are needed.

Effects of 10-kHz Subthreshold Stimulation on Human Peripheral Nerve Activation.

OBJECTIVE: The mechanisms of action of high-frequency stimulation (HFS) are unknown. We investigated the possible mechanism of subthreshold superexcitability of HFS on the excitability of the peripheral nerve. MATERIALS AND METHODS: The ulnar nerve was stimulated at the wrist in six healthy participants with a single (control) stimulus, and the responses were compared with the responses to a continuous train of 5 seconds at frequencies of 500 Hz, 2.5 kHz, 5 kHz, and 10 kHz. Threshold intensity for compound muscle action potential (CMAP) was defined as intensity producing a 100-µV amplitude in ten sequential trials and "subthreshold" as 10% below the CMAP threshold. HFS threshold was defined as stimulation intensity eliciting visible tetanic contraction. RESULTS: Comparing the threshold of single pulse stimulation for eliciting CMAP vs threshold for HFS response and pooling data at different frequencies (500 Hz-10 kHz) revealed a significant difference (p = 0.00015). This difference was most obvious at 10 kHz, with a mean value for threshold reduction of 42.2%. CONCLUSIONS: HFS with a stimulation intensity below the threshold for a single pulse induces axonal superexcitability if applied in a train. It can activate the peripheral nerve and produce a tetanic muscle response. Subthreshold superexcitability may allow new insights into the mechanism of HFS.

Intraoperative bulbocavernosus reflex monitoring in posterior lumbar fusion surgery.

OBJECTIVE: To assess the utility of intraoperative bulbocavernosus reflex (BCR) monitoring in posterior lumbar fusion surgery. METHODS: We retrospectively evaluated 153 patients undergoing posterior lumbar fusion with intraoperative BCR monitoring. Voiding function was assessed at discharge and two follow-ups. RESULTS: BCR was preserved in 151 patients and completely disappeared in two patients at the end of surgery. For patients in whom BCR was preserved, voiding difficulties at discharge and 1-month and 6-month follow-ups were noted in 16 (10.6%), 9 (6.0%), and 0 (0.0%) patients, respectively. However, patients with BCR loss experienced voiding difficulties at all three time-points. Statistical analysis showed a significant difference in voiding between those with preserved and disappeared BCRs at 6 months postoperatively. BCR disappeared during surgery but recovered before the end of surgery in six patients. Among these patients, one experienced transient voiding difficulties postoperatively but with good recovery. However, the other five patients did not experience postoperative voiding difficulties. CONCLUSIONS: BCR had low sensitivity for voiding dysfunction at discharge, but had high accuracy at 6-month follow-up examinations. BCR loss was associated with new voiding dysfunction. SIGNIFICANCE: Intraoperative BCR monitoring is a potentially useful tool for enhancing safety during posterior lumbar fusion by predicting postoperative voiding dysfunction.

Intraoperative monitoring of facial corticobulbar motor evoked potentials: Methodological improvement and analysis of 100 patients.

OBJECTIVE: A) To describe an improved methodology for continuously monitoring the functional integrity of facial nerve by eliciting facial corticobulbar motor-evoked potentials (FCoMEP) and B) To establish the prognosis of facial nerve function based on changes in FCoMEP during skull base surgery. METHODS: Intraoperative monitoring of FCoMEP performed in 100 patients. Previously published methodology has been improved upon by a) doing preoperative mapping of the facial nerve, b) facilitating the corticobulbar tract (CBT) by continuous transcranial electrical stimulation (TES) at 2 Hz repetition rate, c) recording from multiple facial nerve innervated muscles, and d) eliciting blink reflex (BR). We analyzed changes in FCoMEP, comparing them with the clinical facial nerve outcome scored with the House-Brackman (HB) scale. RESULTS: The monitorability rate was 100%. Out of 100 patients, nine presented a new facial deficit after surgery. Eight of these showed significant changes in FCoMEP. In four patients FCoMEPs were lost; they presented a complete facial paralysis from which they did not recover. To discriminate the prognosis of patients, ROC analysis identified a cut-off at 65% for FCoMEPs amplitude decrease with a sensitivity of 89% and specificity of 99%. In four patients FCoMEP showed a decrease in amplitude greater than 65%, and they presented mild/moderate facial paresis that was transient. One patient did not present changes in FCoMEP but had a mild facial paresis from which the patient recovered. CONCLUSIONS: The improved methodology allows the maximum rate of monitorability and minimizes false positive and false negative results. This study shows that prognosis of facial nerve may be reliably established based on FCoMEP parameters. SIGNIFICANCE: We improved the previously described methodology for continuously monitoring the functional integrity of the facial nerve by increasing the monitorability rate, and we describe the impact of FCoMEP intraoperative management of facial nerve. This method may permit establishing the short-term and long-term prognosis of facial nerve function in skull base surgery.

Advances in Intraoperative Neurophysiology During Microvascular Decompression Surgery for Hemifacial Spasm.

Microvascular decompression (MVD) is a widely used surgical intervention to relieve the abnormal compression of a facial nerve caused by an artery or vein that results in hemifacial spasm (HFS). Various intraoperative neurophysiologic monitoring (ION) and mapping methodologies have been used since the 1980s, including brainstem auditory evoked potentials, lateral-spread responses, Z-L responses, facial corticobulbar motor evoked potentials, and blink reflexes. These methods have been applied to detect neuronal damage, to optimize the successful decompression of a facial nerve, to predict clinical outcomes, and to identify changes in the excitability of a facial nerve and its nucleus during MVD. This has resulted in multiple studies continuously investigating the clinical application of ION during MVD in patients with HFS. In this study we aimed to review the specific advances in methodologies and clinical research related to ION techniques used in MVD surgery for HFS over the last decade. These advances have enabled clinicians to improve the efficacy and surgical outcomes of MVD, and they provide deeper insight into the pathophysiology of the disease.

Mapping and monitoring of brainstem surgery.

The surgical morbidity of brainstem lesions is higher than in other areas of the central nervous system because the compact brainstem is highly concentrated with neural structures that are often distorted or even unrecognizable under microscopic view. Intraoperative neurophysiologic mapping helps identify critical neural structures to avoid damaging them. With the trans-fourth ventricular floor approach, identifying the facial colliculi and vagal and hypoglossal triangles enables incising and approaching the brainstem through the safe entry zones, the suprafacial or infrafacial triangle, with minimal injury. Corticospinal tract mapping is adopted in the case of brainstem surgery adjacent to the corticospinal tract. Intraoperative neurophysiologic monitoring techniques include motor evoked potentials (MEPs), corticobulbar MEPs, brainstem auditory evoked potentials, and somatosensory evoked potentials. These provide real-time feedback about the functional integrity of neural pathways, and the surgical team can reconsider and correct the surgical strategy accordingly. With multimodal mapping and monitoring, the brainstem is no longer "no man's land," and brainstem lesions can be treated surgically without formidable morbidity and mortality.

Monitoring cerebellopontine angle and skull base surgeries.

Cerebellopontine angle (CPA) surgery represents a challenge for neurosurgeons due to the high risk of iatrogenic injury of vital neurological structures. Therefore, important efforts in improving the surgical techniques and intraoperative neurophysiology have been made in the last decades. We present a description and review of the available methodologies for intraoperative neuromonitoring and mapping during CPA surgeries. There are three main groups of techniques to assess the functional integrity of the nervous structures in danger during these surgical procedures: (1) Electrical identification or mapping of motor cranial nerves (CNs), which is essential in order to locate the nerve in their different parts during the tumor resection; (2) Monitoring, which provides real-time information about functional integrity of the nervous tissue; and (3) Brainstem reflexes including blink reflex, masseteric reflex, and laryngeal adductor reflex. All these methods facilitate the removal of lesions and contribute to notable improvement in functional outcome and permit on the investigation of their physiopathology in certain neurosurgically treated diseases. Such is the case of hemifacial spasm (HFS). We describe the methodology to evaluate the efficacy of microvascular decompression for HFS treatment at the end of this chapter.

Intraoperative neurophysiology in intramedullary spinal cord tumor surgery.

Intramedullary spinal cord tumor (ISCT) surgery is challenged by a significant risk of neurological injury. Indeed, while most ISCT patients arrive to surgery in good neurological condition due to early diagnosis, many experience some degree of postoperative sensorimotor deficit. Thus, intraoperative neuromonitoring (IONM) is invaluable for providing functional information that helps neurosurgeons tailor the surgical strategy to maximize resection while minimizing morbidity. Somatosensory evoked potential (SEP), muscle motor evoked potential (mMEP), and D-wave monitoring are routinely used to continuously assess the functional integrity of the long pathways within the spinal cord. More recently, mapping techniques have been introduced to identify the dorsal columns and the corticospinal tracts. Intraoperative SEP decline is not a sufficient reason to abandon surgery, since SEPs are very sensitive to anesthesia and surgical maneuvers. Yet, a severe proprioceptive deficit may adversely impact daily life, and the value of SEPs should be reconsidered. While mMEPs are good predictors of short-term motor outcome, the D-wave is the strongest predictor of long-term motor outcome, and its preservation during surgery is essential. Mapping techniques are promising but still need validation in large cohorts of patients to determine their impact on clinical outcome. The therapeutic rather than merely diagnostic value of IONM in spine surgery is still debated, but there is emerging evidence that IONM provides an essential adjunct in ISCT surgery.

Structural changes in brains of patients with disorders of consciousness treated with deep brain stimulation.

Disorders of consciousness (DOC) are one of the major consequences after anoxic or traumatic brain injury. So far, several studies have described the regaining of consciousness in DOC patients using deep brain stimulation (DBS). However, these studies often lack detailed data on the structural and functional cerebral changes after such treatment. The aim of this study was to conduct a volumetric analysis of specific cortical and subcortical structures to determine the impact of DBS after functional recovery of DOC patients. Five DOC patients underwent unilateral DBS electrode implantation into the centromedian parafascicular complex of the thalamic intralaminar nuclei. Consciousness recovery was confirmed using the Rappaport Disability Rating and the Coma/Near Coma scale. Brain MRI volumetric measurements were done prior to the procedure, then approximately a year after, and finally 7 years after the implementation of the electrode. The volumetric analysis included changes in regional cortical volumes and thickness, as well as in subcortical structures. Limbic cortices (parahippocampal and cingulate gyrus) and paralimbic cortices (insula) regions showed a significant volume increase and presented a trend of regional cortical thickness increase 1 and 7 years after DBS. The volumes of related subcortical structures, namely the caudate, the hippocampus as well as the amygdala, were significantly increased 1 and 7 years after DBS, while the putamen and nucleus accumbens presented with volume increase. Volume increase after DBS could be a result of direct DBS effects, or a result of functional recovery. Our findings are in accordance with the results of very few human studies connecting DBS and brain volume increase. Which mechanisms are behind the observed brain changes and whether structural changes are caused by consciousness recovery or DBS in patients with DOC is still a matter of debate.

A New Methodology for Intraoperative Monitoring of the Functional Integrity of the Phrenic Nerve During Cardiothoracic Surgery.

INTRODUCTION: The phrenic nerve could be easily injured during cardiothoracic surgeries because of its anatomical relationships. The aim of this study is to describe a new, feasible, and reproducible methodology to achieve a continuous intraoperative neuromonitoring of the phrenic nerve. METHODS: Consecutive patients who underwent open-chest surgery were included. The recording active electrode was placed 5 cm superior to the tip of the xiphoid process, and a hook wire inserted at the motor point of the ipsilateral hemidiaphragm was used as the reference electrode. RESULTS: We studied 45 patients (92% men, mean age 67 years). Mean height and weight were 167 ± 6.9 cm and 75.6 ± 12.3 kg, respectively. A reproducible compound motor action potential was recorded in 38 (85%) subjects. The mean latency and amplitude values were 9.68 ± 2.40 ms and 1.36 ± 3.83 mV, respectively. No intraoperative events were recorded. CONCLUSIONS: We reported a new methodology which allows the assessment of phrenic nerve functional integrity during surgical procedures.

Neurophysiological monitoring of the laryngeal adductor reflex during cerebellar-pontine angle and brainstem surgery.

OBJECTIVE: To correlate intraoperative changes of the laryngeal adductor reflex (LAR), alone or in combination with corticobulbar motor evoked potential of vocal muscles (vocal-CoMEPs), with postoperative laryngeal function after posterior fossa and brainstem surgery. METHODS: We monitored 53 patients during cerebellar-pontine angle and brainstem surgeries. Vocal-CoMEPs and LAR were recorded from an endotracheal tube with imbedded electrodes or hook-wires electrodes. A LAR significant change (LAR-SC) defined as ≥ 50% amplitude decrement or loss, was classified as either transient or permanent injury to the vagus or medullary pathways by the end of the surgery. RESULTS: All patients with permanent LAR loss (n = 5) or LAR-SC (n = 3), developed postoperative laryngeal dysfunction such as aspiration/pneumonia and permanent swallowing deficits (5.6%). Vocal-CoMEP findings refined postoperative vocal motor dysfunction. All seven patients with transient LAR-SC or loss, reverted by changing the surgical approach, did not present permanent deficits. CONCLUSIONS: Permanent LAR-SCs or loss correlated with postoperative laryngeal dysfunction and predicted motor and sensory dysfunction of the vagus nerve and reflexive medullary pathways. In contrast, a LAR-SC or loss, averted by a timely surgical adjustment, prevented irreversible damage. SIGNIFICANCE: Monitoring of the LAR, with vocal-CoMEPs, may enhance safety to resect complex posterior fossa and brainstem lesions.

Selective dorsal rhizotomy: functional anatomy of the conus-cauda and essentials of intraoperative neurophysiology.

INTRODUCTION: Spasticity is the result of an exaggeration of the monosynaptic muscle stretch reflex due to lesions affecting the central nervous system, in particular an upper motor neuron lesion. Selective dorsal rhizotomy (SDR) is a surgical technique developed to treat spastic diplegia, one of the common forms of cerebral palsy, resulting from the lack of supraspinal inhibitory controls. The aim of SDR is to identify and cut a critical amount of the sensory rootlets, in particular those contributing the most to spasticity, in order to relieve the patient from lower limb spasticity while preserving motor strength and sphincter control. Various surgical techniques to perform SDR have been proposed over time. Similarly, intraoperative neurophysiology (ION)-first introduced by Fasano and colleagues in 1976-is a safe and effective tool to guide the surgeon in the procedure of SDR, but different ION strategies are used by different authors, and the value of ION itself has been questioned. METHODS: The purpose of this paper is to review the anatomo-physiological background of SDR, the historical development of the surgical technique, and the essential principles of ION. RESULTS: While some surgeons privilege a single-level approach and others a multi-level approach, nowadays, there are still neither agreement nor guidelines on the percentage of roots to be cut. Rather, a tailored approach based on both the preoperative functional status as well as intraoperative ION findings seems reasonable. ION is considered not essential to decide the percentage of roots to cut, but it assists to distinguish between ventral and dorsal roots, and to preserve sphincterial function, whenever S2 rootlets are included in SDR. CONCLUSIONS: To optimize the balance between reduction of spasticity and preservation of motor strength while minimizing the neurological damage remains the main goal of SDR.