Extraocular muscle electromyographic recordings for intraoperative monitoring of cranial nerves III, IV, and VI: a single-center experience with intraorbital electrodes.

OBJECTIVE: The objective of this study was to describe the quantitative features of intraoperative electromyographic recordings obtained from cranial nerve III, IV, and VI neuromonitoring using 25-mm intraorbital electrodes, in the larger context of demonstrating the practicality of this technique during neurosurgical cases. METHODS: A 25-mm-long shaft-insulated intraorbital needle electrode is routinely used at the authors' institution for extraocular muscle (EOM) electromyographic monitoring of the inferior rectus, superior oblique, and/or lateral rectus muscles when their function is at risk. Cases monitored between January 1, 2021, and December 31, 2022, were reviewed for patient demographics, tumor location and pathology, EOMs monitored, pre- and postoperative examination, and complications from electrode placement. Compound muscle action potentials on triggered electromyography, as well as neurotonic discharges on free-run electromyography, were described quantitatively. RESULTS: There were 141 cases in 139 patients reviewed during the 24-month time span, with 278 EOMs monitored (inferior rectus/superior oblique/lateral rectus muscles 68/68/142). Triggered electromyography yielded biphasic or triphasic compound muscle action potentials from EOMs with a mean onset latency of 1.51 msec (range 0.94-3.22 msec), mean maximal peak-to-trough amplitude of 1073.93 µV (range 76.75-7796.29 µV), and high specificity for the channel in nearly all cases. Neurotonic discharges were recorded in 30 of the 278 EOMs (with all 3 muscles represented) and associated with a greater incidence of new or worsened ophthalmoparesis (OR 4.62, 95% CI 1.3-16.4). There were 2 cases of small periorbital ecchymosis attributed to needle placement; additionally, 1 case of needle-related intraorbital hematoma occurred after the review period. CONCLUSIONS: The 25-mm shaft-insulated intraorbital electrode facilitates robust and consistent electromyographic recordings of EOMs that are advantageous over existing techniques. Combined with the relative ease of needle placement and low rate of complications, the technique is practical for neuromonitoring during craniotomies.

Two Cases of Periodic Paralysis Associated With MCM3AP Variants.

OBJECTIVES: Periodic paralysis is a rare genetic condition characterized by episodes of neuromuscular weakness, often provoked by electrolyte abnormalities, physiologic stress, physical exertion, and diet. In addition to mutations in genes coding for skeletal muscle ion channels, in 2019, Gustavasson et al discovered that the MCM3AP gene could be responsible for periodic paralysis. In this study, we present 2 individuals with clinical episodes of periodic paralysis who have variants in the MCM3AP gene. METHODS: Two unrelated probands were independently evaluated with clinical, genetic, and electrodiagnostic testing. RESULTS: Proband 1 is a 46-year-old man who presented with decades of ongoing episodic weakness and fatigue, clinically diagnosed with periodic paralysis and supported by electrodiagnostic studies. Proband 2 is a 34-year-old woman with a history of episodic paralysis since childhood. Genetic testing in both individuals revealed potentially pathogenic variants in the MCM3AP gene. CONCLUSIONS: Periodic paralysis is a condition that significantly affects the lives of those diagnosed. The results illustrate that MCM3AP gene variants can been associated with a clinical and electrodiagnostic presentation of periodic paralysis. Additional future research should focus on clarifying any relationship between these genetic variants and the disease, as well as other possible genetic causes.

Clinical, Neurophysiologic, and Pathologic Features in Patients With Early-Onset Postradiation Neuropathy.

OBJECTIVES: The objective of this study was to study early-onset radiation-induced neuropathy reviewing neurologic course, steroid response, and available nerve biopsies. METHODS: Patients coded with radiation-induced neuropathy within 6 months of radiation were reviewed from January 1,1999, to August 31, 2022. Patients had to have electrodiagnostically confirmed neuropathy localized within or distal to radiation fields. Neurologic course and nerve biopsies were reviewed. RESULTS: Twenty-eight patients (16 male and 12 female patients, mean age 63.8 years) were identified. The average radiation dose was 4,659 cGy (range 1,000-7,208). Tumor infiltration was not observed on MRI and PET. Postradiation onsets averaged 2 months (range 0-5). Localizations included brachial (n = 4) plexopathies, lumbosacral (n = 12) plexopathies, radiculopathies (n = 10), and mononeuropathies (n = 2). Neuropathic pain (n = 25) and weakness (n = 25) were typical. The clinical courses were subacute monophasic (n = 14), chronic progressive (n = 8), or static (n = 1), and 5 were without follow-up. Nerve biopsies (n = 8) showed an inflammatory ischemic process with perivascular inflammatory infiltrates (n = 7) or microvasculitis (n = 2). Nine patients, 7 with monophasic courses, received steroid burst therapy with symptom improvement in 8. No patients recovered entirely back to baseline. DISCUSSION: In contrast to chronic radiation-induced neuropathy, early-onset patients most commonly have painful monophasic courses with residual deficits, possibly steroid responsive. An ischemic inflammatory pathogenesis is suggested.

Intraoperative Biceps/Brachialis Stimulation for Snapping Triceps With Ulnar Neuritis.

BACKGROUND AND IMPORTANCE: Snapping of the triceps muscle occurs when a portion of the medial head dislocates over the medial epicondyle with elbow flexion. Resection or redirection of a portion of the triceps muscle is the main surgical treatment. The extent of triceps resection/redirection is difficult to evaluate. A novel intraoperative technique, stimulating the musculocutaneous nerve, to simulate active elbow flexion is proposed to help ensure that the snapping triceps has been adequately treated. CLINICAL PRESENTATION: A patient presented with a several year history of bilateral elbow pain, snapping, and ulnar nerve (UN) paresthesias. Previous staged bilateral subcutaneous UN transpositions were performed at another institution for documented UN dislocation and neuritis. Postoperatively symptoms of painful snapping persisted. Bilateral snapping triceps was diagnosed. The left elbow was reoperated. Intraoperative electrical stimulation of the musculocutaneous nerve was performed to reproduce the snapping triceps. Activation of the biceps/brachialis muscles produced powerful elbow flexion, allowed direct visualization of the forceful snapping triceps, and helped assess the adequacy of muscle resection/redirection. CONCLUSION: Intraoperative biceps/brachialis stimulation can potentially help determine how much triceps muscle should be resected/redirected to treat patients with snapping triceps.

Indications and Technique for the Use of Intraoperative Neuromonitoring in Brachial Plexus Surgery.

Confirming the presence or absence of a functioning nerve root in traumatic brachial plexus injuries is vital in the surgical decision-making process. Intraoperative neuromonitoring can confirm intact rootlets with the use of motor evoked potentials and somatosensory evoked potentials. The purpose of this article is to describe the rationale and details of intraoperative neuromonitoring to provide a basic understanding of its role in decision-making in patients with brachial plexus injuries.

Intraoperative Neuromonitoring for Peripheral Nerve Surgery.

Intraoperative neuromonitoring is a valuable surgical resource that can assist in decision-making during peripheral nerve surgery using real-time electrophysiologic data. By stimulating a nerve and recording action potentials from a point on the nerve ("nerve action potential") or from a muscle ("triggered electromyography"), nerve lesions can be localized and the extent of nerve damage evaluated. The purpose of this article is to provide an overview of the role, indications, and techniques of intraoperative neuromonitoring of peripheral nerve injuries.

Short-Acting Neuromuscular Blockade Improves Inter-rater Reliability of Median Somatosensory Evoked Potentials in Post-cardiac arrest Prognostication.

BACKGROUND: Although median nerve somatosensory evoked potentials are routinely used for prognostication in comatose cardiac arrest survivors, myogenic artifact can reduce inter-rater reliability, leading to unreliable or inaccurate results. To minimize this risk, we determined the benefit of neuromuscular blockade agents in improving the inter-rater reliability and signal-to-noise ratio of SSEPs in the context of prognostication. METHODS: Thirty comatose survivors of cardiac arrest were enrolled in the study, following the request from an intensivist to complete an SSEP for prognostication. Right and left median nerve SSEPs were obtained from each patient, before and after administration of an NMB agent. Clinical histories and outcomes were retrospectively reviewed. The SSEP recordings before and after NMB were randomized and reviewed by five blinded raters, who assessed the latency and amplitude of cortical and noncortical potentials (vs. absence of response) as well as the diagnostic quality of cortical recordings. The inter-rater reliability of SSEP interpretation before and after NMB was compared via Fleiss' κ score. RESULTS: Following NMB administration, Fleiss' κ score for cortical SSEP interpretation significantly improved from 0.37 to 0.60, corresponding to greater agreement among raters. The raters were also less likely to report the cortical recordings as nondiagnostic following NMB (40.7% nondiagnostic SSEPs pre-NMB; 17% post-NMB). The SNR significantly improved following NMB, especially when the pre-NMB SNR was low (< 10 dB). Across the raters, there were three patients whose SSEP interpretation changed from bilaterally absent to bilaterally present after NMB was administered (potential false positives without NMB). CONCLUSIONS: NMB significantly improves the inter-rater reliability and SNR of median SSEPs for prognostication among comatose cardiac arrest survivors. To ensure the most reliable prognostic information in comatose post-cardiac arrest survivors, pharmacologic paralysis should be consistently used before recording SSEPs.

Estimating Intraoperative Neurophysiological Monitoring Rates for Anterior Cervical Discectomy and Fusion: Are Diagnostic or Procedural Codes Accurate?

BACKGROUND: The utility of intraoperative neurophysiological monitoring (IONM) is well established for some spine surgeries (eg, intramedullary tumor resection, scoliosis deformity correction), but its benefit for most degenerative spine surgery, including anterior cervical discectomy and fusion (ACDF), remains debated. National datasets provide "big data" approaches to study the impact of IONM on spine surgery outcomes; however, if administrative coding in these datasets misrepresents actual IONM usage, conclusions will be unreliable. The objective of this study was to compare estimated rates (administrative coding) to actual rates (chart review) of IONM for ACDF at our institution and extrapolate findings to estimated rates from 2 national datasets. METHODS: Patients were included from 3 administrative coding databases: the authors' single institution database, the Nationwide Inpatient Sample (NIS), and the National Surgical Quality Improvement Program (NSQIP). Estimated and actual institutional rates of IONM during ACDF were determined by administrative codes (International Classification of Diseases [ICD] or Current Procedural Terminology [CPT]) and chart review, respectively. National rates of IONM during ACDF were estimated using the NIS and NSQIP datasets. RESULTS: Estimated institutional rates of IONM for ACDF were much higher with CPT than ICD coding (73.2% vs 16.5% in 2019). CPT coding for IONM better approximated actual IONM usage at our institution (74.6% in 2019). Estimated IONM utilization rates for ACDF in national datasets varied widely: 0.76% in CPT-based NSQIP and 18.4% in ICD-based NIS. CONCLUSIONS: ICD coding underestimated IONM usage during ACDF at our institution, whereas CPT coding was more accurate. Unfortunately, the CPT-based NSQIP is nearly devoid of IONM codes, as it has not been a collection focus of that surgical registry. ICD-based datasets, such as the NIS, likely fail to accurately capture IONM usage. Multicenter and/or national datasets with accurate IONM utilization data are needed to inform surgeons, insurers, and guideline authors on whether IONM has benefit for various spine surgery types. CLINICAL RELEVANCE: Currently available national databases based on administrative codes do not accurately reflect IONM usage.

Intraoperative lateral rectus electromyographic recordings optimized by deep intraorbital needle electrodes.

OBJECTIVE: We demonstrate the advantages and safety of long, intraorbitally-placed needle electrodes, compared to standard-length subdermal electrodes, when recording lateral rectus electromyography (EMG) during intracranial surgeries. METHODS: Insulated 25 mm and uninsulated 13 mm needle electrodes, aimed at the lateral rectus muscle, were placed in parallel during 10 intracranial surgeries, examining spontaneous and stimulation-induced EMG activities. Postoperative complications in these patients were reviewed, alongside additional patients who underwent long electrode placement in the lateral rectus. RESULTS: In 40 stimulation-induced recordings from 10 patients, the 25 mm electrodes recorded 6- to 26-fold greater amplitude EMG waveforms than the 13 mm electrodes. The 13 mm electrodes detected greater unwanted volume conduction upon facial nerve stimulation, typically exceeding the amplitude of abducens nerve stimulation. Except for one case with lateral canthus ecchymosis, no clinical or radiographic complications occurred in 36 patients (41 lateral rectus muscles) following needle placement. CONCLUSIONS: Intramuscular recordings from long electrode in the lateral rectus offers more reliable EMG monitoring than 13 mm needles, with excellent discrimination between abducens and facial nerve stimulations, and without significant complications from needle placement. SIGNIFICANCE: Long intramuscular electrode within the orbit for lateral rectus EMG recording is practical and reliable for abducens nerve monitoring.

Quantitative analysis of myokymic discharges in radiation versus nonradiation cases.

INTRODUCTION: Myokymic discharges are classically associated with nerve injury from prior radiation but may occur in other neuromuscular disorders. Using quantitative analysis we aimed to identify the spectrum of conditions in which myokymic discharges are present and determine if there are electrophysiological features that distinguish postradiation from nonradiation causes of myokymia. METHODS: We reviewed the clinical history of all patients examined in our electromyography labs with myokymic discharges recorded from June 2017 to February 2020. Quantitative analysis of each myokymic discharge was performed using a custom MATLAB script, assessing features such as burst frequency, spikes per burst, and burst regularity. RESULTS: Eighty-eight distinct myokymic discharges (70 patients) were analyzed: 51 postradiation recordings from 35 patients and 37 recordings from 35 nonradiation patients. The diagnostic spectrum of nonradiation cases was diverse, with common causes being median neuropathy (n = 8), cervical (n = 7), and lumbar (n = 5) radiculopathy, and motor neuron disease (n = 5). On quantitative analysis, postradiation myokymia had an increased burst-to-silence ratio (median, 0.29; nonradiation, 0.08) and greater peak number (median, 15; nonradiation, 7). Except for one patient with hereditary peripheral nerve hyperexcitability, all patients who had two or more muscles demonstrating myokymic discharges belonged to postradiation group. CONCLUSIONS: Myokymic discharges can be seen in diverse neuromuscular conditions; most common in our cohort was chronic median neuropathy. Postradiation myokymia appears to have distinguishing morphological features when quantitatively analyzed compared with nonradiation cases.

Expanded neuromuscular morbidity in Hodgkin lymphoma after radiotherapy.

Our study aims to quantitate neuromuscular morbidity from radiotherapy in Hodgkin lymphoma including: (i) frequency and (ii) time of onsets for neurological localizations; (iii) degree of disabilities and (iv) number of clinical visits compared to cardiopulmonary Hodgkin lymphoma-radiation complications. Medical records from Mayo Health systems were retrieved; identifying neuromuscular radiation treated Hodgkin lymphoma-complications from 1 January 1994 to 31 December 2016. Of an estimated 4100 post-radiotherapy Hodgkin lymphoma patients, 4.6% (189) were identified with complications. Mean latency to physician visit for symptoms was 23.7 years (range: 1-50). Most commonly identified complications included: head drop 10% (19) with or without myopathy, myopathy 39% (73), plexopathy 29% (54), myelopathy 27% (51) and polyradiculopathy 13% (24). Other findings included benign and malignant nerve sheath tumours 5% (9), phrenic and long thoracic mononeuropathies 7% (14) and compressive spinal meningioma 2% (4). Patients frequently had multiple coexisting complications (single = 76% [144], double = 17% [33], triple = 4% [8], quadruple = 2% [4]). Cardiac 28% (53) and pulmonary 15% (29) complications were also seen in these patients. History of Hodgkin lymphoma was initially overlooked by neurologists (14.3%, 48/336 clinical notes). Hospital and outpatient visits for complications were frequent: neuromuscular 19% (77/411) versus cardiopulmonary 30% (125/411). Testing was largely exclusionary, except when imaging identified secondary malignancy. Modified Rankin score at diagnosis varied: 0-1 (55.8%), 2-3 (5.8%) and 4-5 (38.3%). Neuromuscular complications among post-radiation Hodgkin lymphoma are diverse, occurring in ∼1 of 20 having markedly delayed onsets often eluding diagnosis. Frequent care visits and major morbidity are common. Survivorship recommendations should recognize the diverse neurological complications.

Loss of Mob1a/b in mice results in chondrodysplasia due to YAP1/TAZ-TEAD-dependent repression of SOX9.

Hippo signaling is modulated in response to cell density, external mechanical forces, and rigidity of the extracellular matrix (ECM). The Mps one binder kinase activator (MOB) adaptor proteins are core components of Hippo signaling and influence Yes-associated protein 1 (YAP1) and transcriptional co-activator with PDZ-binding motif (TAZ), which are potent transcriptional regulators. YAP1/TAZ are key contributors to cartilage and bone development but the molecular mechanisms by which the Hippo pathway controls chondrogenesis are largely unknown. Cartilage is rich in ECM and also subject to strong external forces - two upstream factors regulating Hippo signaling. Chondrogenesis and endochondral ossification are tightly controlled by growth factors, morphogens, hormones, and transcriptional factors that engage in crosstalk with Hippo-YAP1/TAZ signaling. Here, we generated tamoxifen-inducible, chondrocyte-specific Mob1a/b-deficient mice and show that hyperactivation of endogenous YAP1/TAZ impairs chondrocyte proliferation and differentiation/maturation, leading to chondrodysplasia. These defects were linked to suppression of SOX9, a master regulator of chondrogenesis, the expression of which is mediated by TEAD transcription factors. Our data indicate that a MOB1-dependent YAP1/TAZ-TEAD complex functions as a transcriptional repressor of SOX9 and thereby negatively regulates chondrogenesis.

Creating three dimensional models of Alzheimer's disease.

BACKGROUND: Alzheimer's disease prevalence will reach epidemic proportions in coming decades. There is a need for impactful educational materials to help patients, families, medical practitioners, and policy makers understand the nature and impact of the disease. Defining an effective workflow to create such models from existing segmentation tools will be a valuable contribution in creating these patient-specific models. RESULTS: A step-by-step workflow was developed and used to take patients' Digital Imaging and Computing in Medicine magnetic resonance brain images through a process resulting in illustrative 3D-printed brain and hippocampus models that clearly demonstrate the progressive degenerative changes caused by Alzheimer's disease. We outline the specific technical steps of auto-segmentation, manual smoothing, Standard Triangle Language file customization, and 3D printing used to create these models. CONCLUSIONS: Our explicated workflow can create effective models of Alzheimer's brains that can be used in patient education, medical education, and policy forums.

Timing-dependent priming effects of tDCS on ankle motor skill learning.

Transcranial direct current stimulation (tDCS) has gained increasing interest in neurorehabilitation with its ability to modulate cortical excitability, and thereby influence neural plasticity and functional recovery. While the beneficial effects of tDCS on motor learning and function have been recognized, there is no clear consensus regarding the timing of the tDCS priming protocol in relation to the intervention especially with respect to lower limb motor learning. Depending on the time of priming in relation to the training task, the neural mechanisms of priming (gating vs. homeostatic plasticity) are different and thereby subsequently affect motor learning. Hence, the aim of this study was to examine the interaction of tDCS with subsequent vs. concurrent motor learning using an ankle visuomotor skill learning paradigm. Twelve healthy participants were tested under three stimulation conditions: (1) anodal tDCS prior to the motor task (tDCS-before), (2) anodal tDCS during the motor task (tDCS-during) and (3) sham tDCS during the motor task (tDCS-sham). Results revealed that tDCS application during practice of a skilled motor task increased motor performance compared to tDCS applied prior to motor practice. Both tDCS groups demonstrated enhanced motor learning when tested 24 hours after practice. We conclude that the priming effects of tDCS are timing dependent, and maybe a critical regulatory feature in determining outcomes of priming with tDCS.