Compound Muscle Action Potential Responses Research Articles

Temporary and highly variable recovery of neuromuscular dysfunction by electrical stimulation in the follow-up of acute critical illness neuromyopathy: a pilot study

BackgroundIn sepsis-associated critical illness neuromyopathy (CIPNM) serial electrical stimulation of motor nerves induces a short-lived temporary recovery of compound muscle action potentials (CMAPs) termed facilitation phenomenon (FP). This technique is different from other stimulation techniques published. The identification of FP suggests a major functional component in acute CIPNM.MethodsFrom our previous study cohort of 18 intensive care unit patients with sepsis associated CIPNM showing profound muscle weakness and low or missing CMAPs on nerve conduction studies, six patients with different severity could be followed. In a pilot sub-study we analyzed the variability of FP during follow up. Over up to 6 weeks we performed 2–6 nerve conduction studies with our novel stimulation paradigm. Motor nerves were stimulated at 0.2–0.5 Hz with 60–100 mA at 0.2–0.5 ms duration, and CMAP responses were recorded. Standard motor nerve conduction velocities (NCV) could be done when utilizing facilitated CMAPs. Needle electromyography was checked once for spontaneous activity to discover potential denervation and muscle fiber degeneration. Serum electrolytes were checked before any examination and corrected if abnormal.ResultsIn all six patients a striking variability in the magnitude and pattern of FP could be observed at each examination in the same and in different motor nerves over time. With the first stimulus most CMAPs were below 0.1 mV or absent. With slow serial pulses CMAPs could gradually recover with normal shape and near normal amplitudes. With facilitated CMAPs NCV measurements revealed low normal values. With improvement of muscle weakness subsequent tests revealed larger first CMAP amplitudes and smaller magnitudes of FP. Needle EMG showed occasional spontaneous activity in the tibialis anterior muscle.ConclusionIn this pilot study striking variability and magnitude of FP during follow-up was a reproducible feature indicating major fluctuations of neuromuscular excitability that may improve during follow-up. FP can be assessed by generally available electrophysiological techniques, even before patients could be tested for muscle strength. Large scale prospective studies of the facilitation phenomenon in CIPNM with or without sepsis are needed to define diagnostic specificity and to better understand the still enigmatic pathophysiology.Trial registration: This trial was registered at the Leipzig University Medical Center in 2021 after approval by the Ethics Committee.

Electromyographic predictors of abducens nerve palsy after endoscopic skull base surgery.

Recovery of abducens nerve palsy (ANP) after endoscopic endonasal skull base surgery (ESBS) has been shown to be potentially predicted by postoperative ophthalmological examination. Triggered electromyography (t-EMG) and free-run electromyography (f-EMG) activity provide an intraoperative assessment of abducens nerve function, but associations with long-term ANP outcomes have not been explored. The objective of this study was to describe intraoperative abducens EMG characteristics and determine whether these electrophysiological profiles are associated with immediately postoperative and long-term ANP outcomes after ESBS. The authors conducted a 5-year (2011-2016) retrospective case-control study of patients who underwent ESBS in whom the abducens nerve was stimulated (t-EMG). Electrophysiological metrics were compared between patients with a new postoperative ANP (cases) and those without ANP (controls). Pathologies included chordoma, pituitary adenoma, meningioma, cholesterol granuloma, and chondrosarcoma. Electrophysiological data included the presence of abnormal f-EMG activity, t-EMG stimulation voltage, stimulation threshold, evoked compound muscle action potential (CMAP) amplitude, onset latency, peak latency, and CMAP duration at various stages of the dissection. Controls were selected such that pathologies were similarly distributed between cases and controls. Fifty-six patients were included, 26 with new postoperative ANP and 30 controls without ANP. Abnormal f-EMG activity (28.0% vs 3.3%, p = 0.02) and lack of response to stimulation (27% vs 0%, p = 0.006) were more frequent in patients with immediately postoperative ANP than in controls. Patients with immediately postoperative ANP also had a lower median CMAP amplitude (35.0 vs 71.2 μV, p = 0.02) and longer onset latency (5.2 vs 2.8 msec, p = 0.04). Comparing patients with transient versus persistent ANP on follow-up, those with persistent ANP tended to have a lower CMAP amplitude (12.8 vs 57 μV, p = 0.07) and higher likelihood of not responding to stimulation at the end of the case (45.5% vs 7.1%, p = 0.06). Abnormal f-EMG was not associated with long-term ANP outcomes. The presence of f-EMG activity, lack of CMAP response to stimulation, decreased CMAP amplitude, and increased CMAP onset latency were associated with immediately postoperative ANP. Long-term ANP outcomes may be associated with t-EMG parameters, including whether the nerve is able to be stimulated once identified and CMAP amplitude. Future prospective studies may be designed to standardize abducens nerve electrophysiological monitoring protocols to further refine operative and prognostic utility.

Minimally invasive extraocular cranial nerve electromyography.

A reluctance to monitor extraocular cranial nerve (EOCN) function has restricted skull base surgery worldwide. Spontaneous and triggered electromyography (EMG) monitoring can be recorded intraoperatively to identify and assess potential cranial nerve injury. Determining the conductive function of EOCNs requires the collection of clear, reliable, and repeatable compound muscle action potentials (CMAPs) secondary to stimulation. EOCN EMG needle electrodes can, although infrequently, cause ocular morbidity including hematoma, edema, and scleral laceration. The aim of this study was to ascertain if minimally invasive 7-mm superficial needle electrodes would record CMAPs as well as standard 13-mm intraorbital electrodes. Conventionally, the authors have monitored EOCN function with intraorbital placement of paired 13-mm needle electrodes into three extraocular muscles: medial rectus, superior oblique, and lateral rectus. A prospective case-control study was performed using shorter (7-mm) needle electrodes. A single minimally invasive electrode was placed superficially near each extraocular muscle and coupled with a common reference. CMAPs were recorded from the minimally invasive electrodes and compared with CMAPs recorded from the paired intraorbital electrodes. The presence or absence of CMAPs was analyzed and compared among EMG recording techniques. A total of 429 CMAPs were analyzed from 71 EOCNs in 25 patients. The experimental setup yielded 167 true-positive (39%), 106 false-positive (25%), 17 false-negative (4%), and 139 true-negative (32%) responses. These values were used to calculate the sensitivity (91%), specificity (57%), positive predictive value (61%), and negative predictive value (89%). EOCN electrodes were placed in 82 total eyes in 58 patients (CMAPs were obtained in 25 patients). Twenty-six eyes showed some degree of edema, bruising, or bleeding, which was transient and self-resolving. Three eyes in different patients had complications from needle placement or extraction including conjunctival hemorrhage, periorbital ecchymosis, and corneal abrasion, ptosis, and upper eyelid edema. Because of artifact contamination, 106 false-positive responses (25%), and 17 false-negative responses (4%), the minimally invasive EMG technique cannot reliably record CMAP responses intraoperatively as well as the intraorbital technique. Less-invasive techniques can lead to an inaccurate EOCN assessment and potential postoperative morbidity. EOCN palsies can be debilitating and lifelong; therefore, the benefits of preserving EOCN function outweigh the potential risks of morbidity from electrode placement. EMG monitoring with intraorbital electrodes remains the most reliable method of intraoperative EOCN assessment.

Prospective Assessment of Risk Factors Influencing Facial Nerve Paresis in Patients after Surgery for Parotid Gland Tumors.

Background and objectives: Facial weakness is the most important complication of parotid gland tumor surgery. The aims of this study are as follows: (1) assessment of the prevalence of postparotidectomy facial nerve dysfunction; (2) clinical and electrophysiological assessment of the facial nerve function before parotidectomy and at 1 and 6 months postoperatively; (3) assessment of the association of postoperative facial palsy with selected risk factors; and (4) assessment of the correlation between the results of clinical and neurophysiological assessments of facial nerve function. Materials and Methods: This study comprised 50 patients (aged 24-75 years) who underwent parotidectomy at the Department of Otolaryngology and Laryngological Oncology in Zabrze, Poland between 2015 and 2017. The evaluation included neurological, clinical and electrophysiological assessments of the facial nerve prior to surgery and at 1 and 6 months postoperatively. Results: No facial palsy was found preoperatively or 6 months postoperatively. Facial nerve dysfunction was found in 74% of patients 1 month postoperatively. In most cases (54%), paresis was mild or moderate (House-Brackmann grades II and III). The results of electrophysiological tests before parotidectomy were either normal or showed some mild abnormalities. We found a statistically significant correlation between the clinical assessment of the facial nerve function (based on the House-Brackmann scale) one month postoperatively and the latency of the CMAP response from the orbicularis oculi and orbicularis oris muscles. In all three studies, a statistically significant correlation was found between the amplitude of the compound muscle action potential (CMAP) of the orbicularis oris muscle and the degree of facial nerve weakness. Conclusions: The factors that may influence the risk of postoperative facial nerve paralysis (prolonged surgical time and the size and location of the tumor other than in the superficial lobe only) may indirectly suggest that surgery-related difficulties and/or surgeon experience could be crucial to surgery safety.

Intramuscular Pressure of Human Tibialis Anterior Muscle Reflects in vivo Muscular Activity.

Intramuscular pressure (IMP) is the fluid hydrostatic pressure generated within a muscle and reflects the mechanical forces produced by a muscle. By providing accurate quantification of interstitial fluid pressure, the measurement of IMP may be useful to detect changes in skeletal muscle function not identified with established techniques. However, the relationship between IMP and muscle activity has never been studied in vivo in healthy human muscles. To determine if IMP is able to evaluate electromechanical performance of muscles in vivo, we tested the following hypotheses on the human tibialis anterior (TA) muscle: (i) IMP increases in proportion to muscle activity as measured by electrical [Compound Muscle Action Potential (CMAP)] and mechanical (ankle torque) responses to activation by nerve stimulation and (ii) the onset delay of IMP (IMPD) is shorter than the ankle torque electromechanical delay (EMD). Twelve healthy adults [six females; mean (SD) = 28.1 (5.0) years old] were recruited. Ankle torque, TA IMP, and CMAP responses were collected during maximal stimulation of the fibular nerve at different intensity levels of electrical stimulation, and at different frequencies of supramaximal stimulation, i.e., at 2, 5, 10, and 20 Hz. The IMP response at different stimulation intensities was correlated with the CMAP amplitude (r2 = 0.94). The area of the IMP response at different stimulation intensities was also significantly correlated with the area of the CMAP (r2 = 0.93). Increasing stimulation intensity resulted in an increase of the IMP response (P < 0.001). Increasing stimulation frequency caused torque (P < 0.001) as well as the IMP (P < 0.001) to increase. The ankle torque EMD [median (interquartile range) = 41.8 (14.4) ms] was later than the IMPD [33.0 (23.6) ms]. These findings support the hypotheses and suggest that IMP captures active mechanical properties of muscle in vivo and can be used to detect muscular changes due to drugs, diseases, or aging.

Friday, September 28, 2018 1:00 PM–2:30 PM abstracts: a new look at imaging: 211. The feasibility of transcutaneous transabdominal stimulation of the lumbosacral nerve roots in lumbar spine surgery

BACKGROUND CONTEXT Intraoperative neuromonitoring during lumbar spine surgery has primarily relied on triggered and/or free-run electromyography (EMG) in mapping neural structures in the surgical field. Transcranial motor evoked potentials (MEPs) provide monitoring of the spinal cord, with nonspecific myotome activation following. Their application in lumbar procedures is increasingly being considered and utilized for cauda equina and nerve root monitoring. MEPs are more sensitive to detect a variety of spinal cord injury mechanisms, including ischemia, and, as such, have a higher sensitivity and specificity than stimulated electromyography (sEMG) with a higher postoperative predictive value for spinal cord deficits. The drawbacks of MEPs include the requirement for total intravenous anesthesia (TIVA), difficulty in achieving complete and reproducible baseline stimulation responses in relevant myotomes, lack of agreement on alarm criteria, and the potential for MEP-related injuries like tongue lacerations. Most importantly, MEPs are not validated in isolated lumbar applications, where the cauda equina and nerve roots, rather than the spinal cord, are at risk. There have, however, been several studies that have evaluated the utility of MEPs in XLIF. PURPOSE The purpose of this study was to assess the feasibility of using transabdominal muscle action potential (TMAPTM, NuVasive, Inc. San Diego, CA, USA) generation in lumbar fusions as an alternative to transcranial MEPs. This first analysis focuses on the feasibility and reproducibility of using this monitoring modality to activate individual lower-extremity myotomes. STUDY DESIGN/SETTING A prospective, multicenter, observational evaluation of the feasibility and utility of lower extremity nerve root compound muscle action potential monitoring in response to transabdominal stimulation was undertaken. Enrollment was completed at 15 US sites. Primary inclusion criteria included patients being at least 18 years of age who were undergoing extreme lateral interbody fusion (XLIF, NuVasive, Inc., San Diego, CA, USA) between L2-3 and L4-5, inclusive of L4-5. PATIENT SAMPLE A total of 335 patients were enrolled. Mean age of the patients was 64 years, 60% of patients were female, and patients had an average BMI of 30.6. A total of 524 levels of XLIF were treated in the 335 patients (mean, 1.6 per patient). The most common indication for surgery was spondylolisthesis (79%). OUTCOME MEASURES TMAP stimulation thresholds (mA) and myotome measurements (using a 30mV CMAP amplitude threshold) were taken prior to the initial incision at baseline, throughout the procedure at five minute intervals, and then again after closure. METHODS The technique for TMAP generation included the application of standard EMG bipolar pair recording electrodes on five myotomes per leg, one pair each on adductor magnus, vastus lateralis, vastus medialis, tibialis anterior, and biceps femoris. Stimulation was delivered transabdominally at approximately the superior end of the cauda equina. This stimulation pathway was selected to enable direct depolarization of the entire lumbosacral motor pathway as superior as possible to the surgical corridor, while remaining inferior to the spinal cord. The stimulation cathode was placed on the patient's posterior midline near the L1-2 disc space. The stimulation anode was placed on the patient's anterior midline superior to the umbilicus. For each TMAP stimulation, a series of pulses was applied with increasing stimulation intensity to identify the minimum stimulation intensity (threshold) required to elicit a compound muscle action potential (CMAP) for each individual myotome. RESULTS At baseline, all patients were stimulated transabdominally and a discrete CMAP response from at least one lower extremity myotome recorded. Out of a total of 3,350 myotomes (five bilateral myotomes per patient, per stimulation time point) stimulated at baseline, 3,255 (97.2%) yielded a CMAP in response to TMAP stimulation. At surgical closure, all patients had at least one myotome that was able to be activated with TMAP, with 94.6% of myotomes (3,169 myotomes) yielding a CMAP. Mean baseline stimulation threshold was 570mA (standard deviation (stdev), 192mA) with mean stimulation at closure of 599mA (stdev, 202mA), p CONCLUSIONS These data suggest that lower extremity nerve root monitoring can be accomplished reproducibly with TMAPs without the associated challenges or risk of traditional transcranial MEPs. While the TMAP technique using a novel stimulation application can supplement neural mapping via evoked EMG during XLIF, it also has potential utility in all lumbar surgical procedures where nerve roots are at risk. Subsequent analyses from this project will include injury detection and avoidance automation assessments.

Electrical stimulation-based nerve location prediction for cranial nerve VII localization in acoustic neuroma surgery.

IntroductionCranial nerve (CN) VII localization is a critical step during acoustic neuroma surgery because the nerve is generally hidden due to the tumor mass. The patient can suffer from Bell's palsy if the nerve is accidentally damaged during tumor removal. Surgeons localize CN VII by exploring the target area with a stimulus probe. Compound muscle action potentials (CMAPs) are elicited when the probe locates the nerve. However, false positives and false negatives are possible due to unpredictable tissue impedance in the operative area. Moreover, a single CMAP amplitude is not correlated with probe‐to‐nerve distance.ObjectivesThis paper presents a new modality for nerve localization. The probe‐to‐nerve distance is predicted by the proposed nerve location prediction model.MethodsInput features are extracted from CMAP responses, tissue impedance, and stimulus current. The tissue impedance is calculated from the estimated resistance and capacitance of the tissue equivalent circuit. In this study, experiments were conducted in animals. A frog's sciatic nerve and gastrocnemius were used to represent CN VII and facial muscle in humans, respectively. Gelatin (2.8%) was used as a mock material to mimic an acoustic neuroma. The %NaCl applied to the mock material was used to emulate uncontrollable impedance of tissue in the operative area.ResultsThe 10‐fold cross‐validation results revealed an average prediction accuracy of 86.71% and an average predicted error of 0.76 mm compared with the measurement data.ConclusionThe proposed nerve location prediction model could predict the probe‐to‐nerve distance across various impedances of the mock material.

Too Weak to Breathe: An Odd Case of Lambert Eaton Myasthenic Syndrome

SESSION TITLE: Critical Care 3 SESSION TYPE: Affiliate Case Report Poster PRESENTED ON: Tuesday, October 31, 2017 at 01:30 PM - 02:30 PM INTRODUCTION: Lambert Eaton Myasthenic Syndrome (LEMS) is a rare autoimmune disorder of the neuromuscular junction characterized by the presence of antibodies against voltage gated calcium channels (VGCC) often associated with an underlying neoplasm. CASE PRESENTATION: 52 year old Caucasian female was admitted to an outside hospital with lethargy, shortness of breath and was intubated for acute hypercapnic respiratory failure which ultimately resolved and she was extubated. Her discharge diagnosis was presumed obstructive sleep apnea. Three weeks later she presented to our hospital with the same symptoms. Physical exam was significant for diminished breath sounds bilaterally and musculoskeletal exam was normal on presentation. Arterial blood gas was 7.26/79/118/35 after 30 minutes on non-invasive positive pressure ventilation, prompting intubation. On the ventilator she was awake and alert without sedation, but failed repeated breathing trials due to apnea, low tidal volumes and a negative inspiratory force of -10 cmH2O. Her persistant, profound and unexplained respiratory muscle weakness, raised concerns for a neuromuscular disorder and neurology was consulted. Electromyogram and nerve conduction studies revealed a post exercise increase in compound muscle action potential response > 200%, her VGCC antibodies were positive and acetylcholine receptor antibodies were negative. Computerized Tomography of the chest demonstrated a right suprahilar mass with a paratracheal lymph node which was hypermetabolic on Positron Emission Tomography. Endobronchial Ultrasound with biopsy of the lymph node confirmed small cell lung carcinoma. She was treated with pyridostigmine and plasma exchange with excellent response and was extubated several days later. She received three cycles of etoposide, cisplatin, chest radiation and is currently on mestinon and 3,4 diaminopyridine for her LEMS. DISCUSSION: LEMS classically presents as proximal muscle weakness, autonomic dysfunction and areflexia. Respiratory failure is a common primary manifestation of Myasthenia Gravis, however the literature rarely documents LEMS as presenting this way. This case highlights the importance of considering occult neuromuscular diseases in cases of unexplained respiratory failure even if other classical symptoms such as muscle weakness are absent. Our patient had repeated episodes of respiratory failure requiring intubation that was initially misdiagnosed, leading to missed treatment opportunities, a poor quality of life and an unchecked pulmonary malignancy. CONCLUSIONS: LEMS often presents early in the neoplastic course, thus diagnosis has important implications. Treatment of LEMS can be effective in relieving the neuromuscular symptoms and early detection of the underlying malignancy can be lifesaving. Reference #1: Fatima. U., Shah. T., Dedhia.P., Devine. S., Lambert Eaton Syndrome: Unique Presentation of the Disease with Isolated Respiratory Muscle Weakness. CHEST. Abstract 326A. October 2013. DISCLOSURE: The following authors have nothing to disclose: Caryn Brehm, Christopher Barrios, James Caress, Daniel Files, Daniel LoVerde No Product/Research Disclosure Information

Altered activation of the diaphragm in late-onset Pompe disease

Pompe disease is an inherited neuromuscular disorder that affects respiratory function and leads to dependence on external ventilatory support. We studied the activation of the diaphragm using bilateral phrenic magnetic stimulation and hypothesized that diaphragm compound muscle action potential (CMAP) amplitude and evoked transdiaphragmatic pressure (Twitch PDI) would correlate to disease severity. Eight patients with late onset Pompe disease (LOPD, aged 14–48 years) and four healthy control subjects completed the tests. Maximal Twitch PDI responses were progressively reduced in patients with LOPD compared to control subjects (1.4–17.1cm H2O, p<0.001) and correlated to voluntary functional tests (p<0.05). Additionally, CMAP amplitude (mA) was lower in the patients who used nighttime or fulltime ventilatory support, when compared to controls and patients who used no ventilatory support (p<0.005). However, the normalized (%peak) Twitch PDI and CMAP responses were similar between patients and controls. This suggests a loss of functional phrenic motor units in patients, with normal recruitment of remaining motor units.

Electrophysiological Motor Unit Number Estimation (MUNE) Measuring Compound Muscle Action Potential (CMAP) in Mouse Hindlimb Muscles

Compound muscle action potential (CMAP) and motor unit number estimation (MUNE) are electrophysiological techniques that can be used to monitor the functional status of a motor unit pool in vivo. These measures can provide insight into the normal development and degeneration of the neuromuscular system. These measures have clear translational potential because they are routinely applied in diagnostic and clinical human studies. We present electrophysiological techniques similar to those employed in humans to allow recordings of mouse sciatic nerve function. The CMAP response represents the electrophysiological output from a muscle or group of muscles following supramaximal stimulation of a peripheral nerve. MUNE is an electrophysiological technique that is based on modifications of the CMAP response. MUNE is a calculated value that represents the estimated number of motor neurons or axons (motor control input) supplying the muscle or group of muscles being tested. We present methods for recording CMAP responses from the proximal leg muscles using surface recording electrodes following the stimulation of the sciatic nerve in mice. An incremental MUNE technique is described using submaximal stimuli to determine the average single motor unit potential (SMUP) size. MUNE is calculated by dividing the CMAP amplitude (peak-to-peak) by the SMUP amplitude (peak-to-peak). These electrophysiological techniques allow repeated measures in both neonatal and adult mice in such a manner that facilitates rapid analysis and data collection while reducing the number of animals required for experimental testing. Furthermore, these measures are similar to those recorded in human studies allowing more direct comparisons.

Electrophysiological Motor Unit Number Estimation (MUNE) Measuring Compound Muscle Action Potential (CMAP) in Mouse Hindlimb Muscles.

Compound muscle action potential (CMAP) and motor unit number estimation (MUNE) are electrophysiological techniques that can be used to monitor the functional status of a motor unit pool in vivo. These measures can provide insight into the normal development and degeneration of the neuromuscular system. These measures have clear translational potential because they are routinely applied in diagnostic and clinical human studies. We present electrophysiological techniques similar to those employed in humans to allow recordings of mouse sciatic nerve function. The CMAP response represents the electrophysiological output from a muscle or group of muscles following supramaximal stimulation of a peripheral nerve. MUNE is an electrophysiological technique that is based on modifications of the CMAP response. MUNE is a calculated value that represents the estimated number of motor neurons or axons (motor control input) supplying the muscle or group of muscles being tested. We present methods for recording CMAP responses from the proximal leg muscles using surface recording electrodes following the stimulation of the sciatic nerve in mice. An incremental MUNE technique is described using submaximal stimuli to determine the average single motor unit potential (SMUP) size. MUNE is calculated by dividing the CMAP amplitude (peak-to-peak) by the SMUP amplitude (peak-to-peak). These electrophysiological techniques allow repeated measures in both neonatal and adult mice in such a manner that facilitates rapid analysis and data collection while reducing the number of animals required for experimental testing. Furthermore, these measures are similar to those recorded in human studies allowing more direct comparisons.

Electrophysiological biomarkers in spinal muscular atrophy: proof of concept

ObjectivePreclinical therapies that restore survival motor neuron (SMN) protein levels can dramatically extend survival in spinal muscular atrophy (SMA) mouse models. Biomarkers are needed to effectively translate these promising therapies to clinical trials. Our objective was to investigate electrophysiological biomarkers of compound muscle action potential (CMAP), motor unit number estimation (MUNE) and electromyography (EMG) using an SMA mouse model.MethodsSciatic CMAP, MUNE, and EMG were obtained in SMNΔ7 mice at ages 3–13 days and at 21 days in mice with SMN selectively reduced in motor neurons (ChATCre). To investigate these measures as biomarkers of treatment response, measurements were obtained in SMNΔ7 mice treated with antisense oligonucleotide (ASO) or gene therapy.ResultsCMAP was significantly reduced in SMNΔ7 mice at days 6–13 (P < 0.01), and MUNE was reduced at days 7–13 (P < 0.01). Fibrillations were present on EMG in SMNΔ7 mice but not controls (P = 0.02). Similar findings were seen at 21 days in ChATCre mice. MUNE in ASO-treated SMNΔ7 mice were similar to controls at day 12 and 30. CMAP reduction persisted in ASO-treated SMNΔ7 mice at day 12 but was corrected at day 30. Similarly, CMAP and MUNE responses were corrected with gene therapy to restore SMN.InterpretationThese studies confirm features of preserved neuromuscular function in the early postnatal period and subsequent motor unit loss in SMNΔ7 mice. SMN restoring therapies result in preserved MUNE and gradual repair of CMAP responses. This provides preclinical evidence for the utilization of CMAP and MUNE as biomarkers in future SMA clinical trials.

Riluzole exerts central and peripheral modulating effects in amyotrophic lateral sclerosis

Riluzole, a benzothiazole derivative, has been shown to be effective in prolonging survival in amyotrophic lateral sclerosis. The mechanisms by which riluzole exerts neuroprotective effects in amyotrophic lateral sclerosis remains to be fully elucidated, although inhibition of glutamatergic transmission and modulation of Na+ channel function have been proposed. In an attempt to determine the mechanisms by which riluzole exerts neuroprotective effects, in particular to dissect the relative contributions of inhibition of glutamatergic transmission and Na+ channel modulation, the present study utilized a combination of cortical and peripheral axonal excitability approaches to monitor changes in excitability and function in patients with amyotrophic lateral sclerosis. Cortical assessment was undertaken by utilising the threshold tracking transcranial magnetic stimulation (TMS) technique and combined with peripheral axonal excitability studies in 25 patients with amyotrophic lateral sclerosis. Studies were performed at baseline and repeated when patients were receiving riluzole 100 mg/day. At the time of second testing all patients were tolerating the medication well. Motor evoked potential and compound muscle action potential responses were recorded over the abductor pollicis brevis muscle. At baseline, features of cortical hyperexcitability were evident in patients with amyotrophic lateral sclerosis, indicated by marked reduction in short interval intracortical inhibition (P < 0.001) and cortical silent period duration (P < 0.001), as well as an increase in the motor evoked potential amplitude (P < 0.01). Riluzole therapy partially normalized cortical excitability by significantly increasing short interval intracortical inhibition (short interval intracortical inhibitionbaseline 0.5 ± 1.8%; short interval intracortical inhibitionON riluzole 7.9 ± 1.7%, P < 0.01). In contrast, riluzole did not exert any modulating effect on cortical silent period duration (P = 0.45) or motor evoked potential amplitude (P = 0.31). In terms of peripheral nerve function, axonal excitability studies established that, relative to control subjects, patients with amyotrophic lateral sclerosis had significant increases in depolarizing threshold electrotonus [amyotrophic lateral sclerosisbaseline TEd (90-100 ms) 49.1 ± 1.8%; controlsTEd (90-100 ms) 45.2 ± 0.6%, P < 0.01] and superexcitability (amyotrophic lateral sclerosisbaseline 30.1 ± 2.3%; control subjects 23.4 ± 1.0%, P < 0.01) at baseline. Following institution of riluzole therapy there was a significant reduction in superexcitability (amyotrophic lateral sclerosisbaseline 30.1 ± 2.3%; amyotrophic lateral sclerosisON riluzole 27.3 ± 2.3%, P < 0.05) and refractoriness at 2 ms (amyotrophic lateral sclerosisbaseline 98.7 ± 10.7%; amyotrophic lateral sclerosisON riluzole 67.8 ± 9.3%, P < 0.001). In conclusion, the present study has established that riluzole exerts effects on both central and peripheral nerve function, interpreted as partial normalization of cortical hyperexcitability and reduction of transient Na+ conductances. Taken together, these findings suggest that the neuroprotective effects of riluzole in amyotrophic lateral sclerosis are complex, with evidence of independent effects across both compartments of the nervous system.

Dose and timing effect of etomidate on motor evoked potentials elicited by transcranial electric or magnetic stimulation in the monkey and baboon

Etomidate has been shown to both enhance and depress the cortical amplitude of somatosensory evoked potentials (SSEP) depending on the dose used. Similar amplitude increases with etomidate and motor evoked potentials resulting from cortical magnetic (tcMMEP) and electric (tcEMEP) stimulation have not been consistent. We used a primate model to elucidate the time and dose characteristics of the effect. tcMMEP and tcEMEP were characterized during bolus injections of 0.1-1.8 mg/kg etomidate in 10 adult cynomologous monkeys during a baseline anesthesia with a continuous ketamine infusion. Responses were assessed by measuring the amplitude and onset latency of the hypothenar compound action potential response. In a second experiment the epidural and hypothenar response to tcEMEP was recorded under 0.3% isoflurane anesthesia and following intravenous injection of 0.05-0.35 mg/kg etomidate. Cortical stimulation was accomplished using a Cadwell MES-10 (tcMMEP) and Digitimer D180 (tcEMEP). The amplitude of the hypothenar muscle response was increased for tcEMEP and tcMMEP at 20 min following 0.1 mg/kg etomidate in the monkey. The amplification of the tcMMEP response was significantly greater than the tcEMEP response (1.95 + 0.62 SD vs. 1.43 + 0.68 SD, P = 0.023). Responses at higher doses were all below baseline. The tcMMEP response was significantly smaller than the tcEMEP at doses above 0.9 mg/kg (all P<0.001). The onset latency values were not significantly increased at any dose or time. The epidural recording demonstrated a large increase in the number of I waves compared to the isoflurane baseline. This study demonstrates that a low dose (0.1 mg/kg) of etomidate increases the com- pound muscle action potential (CMAP) amplitude for tcEMEP and tcMMEP in the monkey whereas higher doses decrease the amplitude. Epidural recordings demonstrate a marked increase in the number of I waves consistent with a cortical effect similar to the postulated effect that results in amplification of the cortical SSEP. This suggests the amplitude loss in the hypothenar muscles may be due to depression of the spinal cord by etomidate. The CMAP response amplification at low doses was greater in tcMMEP than tcEMEP and the depression at higher doses was more with the tcMMEP technique consistent with the greater dependence of the tcMMEP technique on synaptic activation.

Predicting Recovery After Fibular Nerve Injury

Although it is important to have strong predictors of outcome in peripheral mononeuropathies so that appropriate management can be instituted early, little is known about the prognostic value of electrodiagnostic results for these lesions. Our objective in this study was to evaluate the prognostic value of electrodiagnostic studies in fibular neuropathy. In this retrospective study, 39 of 138 subjects with fibular neuropathy met the inclusion criteria. Electrodiagnostic results at the time of testing were evaluated for their value in predicting outcome. Good outcome was defined as grade 4 or higher strength on the Medical Research Council Scale in ankle dorsiflexion. Compound muscle action potential responses from extensor digitorum brevis and tibialis anterior predicted prognosis: 81% of subjects with any tibialis anterior response and 94% with any extensor digitorum brevis response had a good outcome vs. those with absent responses (46% and 52%, respectively). Importantly, there was still a high likelihood of good outcome with absent compound muscle action potential responses. Tibialis anterior compound muscle action potential gave additional prognostic information when extensor digitorum brevis response was absent. Recruitment in tibialis anterior was predictive in traumatic cases. All patients with nontraumatic compression had a good outcome. We conclude that electrodiagnostic studies produce useful prognostic information in fibular neuropathy, particularly in traumatic cases.

Optimal Placement of Recording Electrodes for Quantifying Facial Nerve Compound Muscle Action Potential

To analyze optimal placement of recording-needle electrodes surrounding the eye and lip for facial nerve monitoring by identifying the maximum compound muscle action potential (CMAP) recorded by electrode pairs of different spatial configurations. Prospective clinical trial. Ambulatory surgery at a tertiary care center. Thirty adults undergoing chronic ear surgery such as tympanoplasty, mastoidectomy, ossicular chain reconstruction, stapedectomy, and cochlear implantation. Facial nerve monitoring. Suprathreshold (threshold + 0.2 V) CMAP responses are recorded from referential paired needle electrodes placed into orbicularis oculi (1.5-cm spacing; n = 15) and orbicularis oris (1.0-cm spacing; n = 15) muscles. Optimal recording electrode placement is inferred by identifying the maximum evoked CMAP amplitude. For the eye, placement of electrodes by the orbital rim and into the upper eyelid is significantly better (Friedman test; p < 0.01) than the other 2 configurations. For the lip, placement of electrodes into the oral commissure and either the upper or lower lip is satisfactory because there is no statistically significant difference among the configurations (Friedman test; p > 0.2). Recording electrode placement configurations that capture the largest CMAP responses are recommended as standard operating procedure for intraoperative facial nerve monitoring.

Anterior interosseous nerve conduction study: Normative data

Neurophysiological techniques assessing anterior interosseous nerve (AIN) function and employing surface electrode recordings from the flexor pollicis longus (FPL), have been limited by technical difficulties. The aim of this study was to describe a surface electrode recording technique of investigating the AIN by recording compound muscle action potentials (CMAPs) from FPL. CMAP responses exhibited a negative onset, suggesting that they originated from FPL, and this was confirmed by needle recording. Normative data has been established that may prove useful in future studies assessing pathological involvement of the anterior interosseous nerve.

The stimulus–response curve and motor unit variability in normal subjects and subjects with amyotrophic lateral sclerosis

The behavior and stability of motor units (MUs) in response to electrical stimulation of different intensities can be assessed with the stimulus-response curve, which is a graphical representation of the size of the compound muscle action potential (CMAP) in relation to stimulus intensity. To examine MU characteristics across the whole stimulus range, the variability of CMAP responses to electrical stimulation, and the differences that occur between normal and disease states, the curve was studied in 11 normal subjects and 16 subjects with amyotrophic lateral sclerosis (ALS). In normal subjects, the curve showed a gradual increase in CMAP size with increasing stimulus intensity, although one or two discrete steps were sometimes observed in the upper half of the curve, indicating the activation of large MUs at higher intensities. In ALS subjects, large discrete steps, due to loss of MUs and collateral sprouting, were frequently present. Variability of the CMAP responses was greater than baseline variability, indicating variability of MU responses, and at certain levels this variability was up to 100 microVms. The stimulus-response curve shows differences between normal and ALS subjects and provides information on MU activation and variability throughout the curve.

Congenital Myasthenic Syndrome: Presentation, Electrodiagnosis, and Muscle Biopsy

We report 10 children with congenital myasthenic syndromes diagnosed by clinical features, electrodiagnostic studies, and response to acetylcholinesterase inhibitors. Age at diagnosis (mean = 4.4 years; range 0.2-10 years) correlated with age fatigue was recognized. Symptoms at presentation included mild gross motor development delay (7/10), speech articulation difficulty (5/10), and respiratory and feeding difficulties resulting in poor growth in 7 of 10 children. None of the five children with possible presynaptic abnormalities had decremental compound muscle action potential responses to 2 Hz repetitive nerve stimulation. Instead, electrodiagnostic studies showed a more than 100% increment of compound muscle action potential amplitude during 50 Hz repetitive nerve stimulation in two children and sustained compound muscle action potential decrement to 2 Hz repetitive nerve stimulation after depletion (10 Hz stimulation for 10 min) in four children. Muscle biopsies (n = 7) showed mild to severe variation in fiber size. Our experience suggests that many children with congenital myasthenic syndromes might be undiagnosed because of atypical presentation and because additional electrophysiologic studies are required.

Congenital Myasthenic Syndrome: Presentation, Electrodiagnosis, and Muscle Biopsy

We report 10 children with congenital myasthenic syndromes diagnosed by clinical features, electrodiagnostic studies, and response to acetylcholinesterase inhibitors. Age at diagnosis (mean = 4.4 years; range 0.2–10 years) correlated with age fatigue was recognized. Symptoms at presentation included mild gross motor development delay (7/10), speech articulation difficulty (5/10), and respiratory and feeding difficulties resulting in poor growth in 7 of 10 children. None of the five children with possible presynaptic abnormalities had decremental compound muscle action potential responses to 2 Hz repetitive nerve stimulation. Instead, electrodiagnostic studies showed a more than 100% increment of compound muscle action potential amplitude during 50 Hz repetitive nerve stimulation in two children and sustained compound muscle action potential decrement to 2 Hz repetitive nerve stimulation after depletion (10 Hz stimulation for 10 min) in four children. Muscle biopsies ( n = 7) showed mild to severe variation in fiber size. Our experience suggests that many children with congenital myasthenic syndromes might be undiagnosed because of atypical presentation and because additional electrophysiologic studies are required.