INTRODUCTION/AIMS:Quantitative analysis should be useful to all electrodiagnostic medical consultants (EMC). We tested a beta version of the audio-visual electromyography (AVEMG) method that quantifies the audio and visual characteristics of the interference pattern (IP) signal assessed by the EMC. METHODS:IP was recorded from multiple sites in 10 commonly tested upper and lower limb muscles. For each 200 ms epoch, AVEMG measured its Amplitude, Fullness and Pitch. Pitch reflects the sound characteristics, e.g., dull, sharp. The firing rate of motor units and discreteness of the pattern was also assessed. Reference (RVs) values were defined for Amplitude and Pitch based on Fullness of the pattern using recordings from 10 to 14 normal subjects. Normal and abnormal muscles were tested in 36 patients referred to the laboratory (139 muscles). The concordance between subjective assessment and AVEMG was assessed by a χ 2 test. RESULTS:AVEMG successfully rejected most epochs with noise, interference, spontaneous activity, insertional activity and needle artifacts. RVs differed among muscles. As example, the first dorsal interosseous and triceps had the highest Amplitude in upper limb muscles. AVEMG was abnormal in 80% of studies considered abnormal by subjective assessment. The association between subjective assessment and AVEMG was statistically significant (χ 2 (1, N = 139) = 59, p < 0.0001). DISCUSSION:AVEMG provides real time quantitation in the background and does not interfere with workflow or add examination time or complexity to the routine needle EMG examination. It will be of interest to further assess its value by refining RVs and performing multicenter studies with operators having different skill levels.

INTRODUCTION/AIMS:Extrapolated reference values (E-Ref) is a method to extract reference values (RVs) from a mixed data set (i.e., a data set containing normal and abnormal findings). This is an attractive way for any laboratory to develop their own RVs. Since its original description, we have made enhancements to the E-Ref method. Due to growing interest in this methodology, we describe our current version of the algorithm and interpretation of its results. METHODS:The cumulative distribution function (CDF) is the foundation of E-Ref methodology. Computer simulations were used to generate "normal" and mixed data sets of conduction velocity. The E-Ref algorithm was revised based on the analysis of CDF in the simulation studies. Bootstrap analysis was performed to assess the variability of estimates and finalize the RV. Median motor nerve conduction parameters from patient studies were analyzed. RESULTS:The CDF shows a "plateau" that contains the majority of the normal data even in a mixed data set. The mean of data in the plateau approximated the mean of "normal" measurements. The difference between the maximum and minimum in the plateau was close to two standard deviations (SDs). DISCUSSION:The new algorithm establishes three ranges to define findings: definitely normal, definitely abnormal, and borderline. This is consistent with the customary clinical thought process where abnormalities are not "black and white." Bootstrap analysis must be performed for reliable estimates. This may be useful to assess the adequacy of the sample size.

Objectives The purpose of this study is to introduce a new analytical technique on repeater F waves (RFws) using compound muscle action potential (CMAP) scan and new features to differentiate the nerves innervating hand muscles. Methods Twenty-four healthy subjects participated in the CMAP scan study. Tests were performed on the abductor pollicis brevis (APB) and abductor digit minimi (ADM) muscles. RFws were extracted using unsupervised machine learning and analyzed through conventional characteristics such as amplitude, latency, indices of F repeaters and total F repeaters, as well by new variables, including relative stimulus intensity (ReSI), relative F/M ratio (RF/MR), and range of stimulation intensity (RaSI). Results Significantly higher indices of F repeaters (APB: 18.42±4.92 %, ADM: 13.58±4.68 %, p < 0.005) and total F repeaters (APB: 34.75±7.8 %, ADM: 26.67±8.56 %, p < 0.005) were observed in the APB compared with the ADM muscles. The ReSI (Z = 13.81, p < 0.001) and RaSI (Z=-2.46, p < 0.05) showed significant differences between the two muscles. Discussion and Conclusion This study provides normative data for RFws based on the CMAP scan recording and identifies different characteristics of repeaters between APB and ADM muscles. Findings of the study improve understanding of motoneuron physiological properties in hand muscles. The CMAP scan-based F wave analysis can be combined with motor unit number estimation technique to provide insights into surviving motoneuron function in neurological disorders.

INTRODUCTION/AIMS:To add objectivity to the routine needle electromyography examination, we describe an "Augmented Intelligence" based interference pattern (IP) analysis method that mimics the subjective assessment by quantifying IP fullness, discreteness, amplitude, pitch, and motor unit firing rate (FR). METHODS:IP recordings from 20 control subjects and other patients with neuropathy and myopathy were analyzed. The IP was divided into three groups: low, intermediate, and full to mimic visual appearance. Reference values (RVs) were defined for each group. "Fence" pattern was defined based on the discreteness and amplitude. Upper limit of FR was defined. Various technical artifacts were detected and excluded from analysis. RESULTS:In control subjects, a total of 2435 recordings from 119 commonly tested muscles were analyzed. The single set of RVs was satisfactory across the tested muscles. Amplitude increased when the pattern changed from low to full. Pitch did not correlate with fullness and its RVs were same for all groups. In patients with neuropathy, an intermediate or low pattern, high amplitude, fence pattern, low pitch, and high FR were demonstrated. In patients with myopathy, a full pattern with low amplitude and high pitch was demonstrated. DISCUSSION:The algorithm makes simple measurements that are readily interpreted by the electromyographer. In this respect, it augments analysis by providing quantitative data. If implemented in an "on-line" manner, it can provide guidance to the operator without adding to the procedure time or changing the recording technique. The measurements can also be included in the report to support the study's findings.

Abnormal spontaneous single muscle fiber generators (ASMFGs) in skeletal muscle are characterized in electrodiagnostic medicine (EDM) as: increased insertional activity (IncrIA), fibrillation potentials (FPs: triphasic and biphasic spike forms and the positive sharp wave [PSW] configuration), complex repetitive discharges (CRDs), and myotonic discharges (MyoDs). To date, there has not been a comprehensive, correlative categorization with respect to the fundamental anatomic/electrophysiologic origin and specific discharge characteristics for the above-noted waveforms. The underlying proposed basis for all ASMFGs is effectively an unstable resting membrane potential (RMP). This is predicated on specific combinations of ion channel dysfunctions that in turn generate unique stereotypical discharge patterns. The latter is consequent to ion channel disequilibrium, with each pathologic entity's waveform having specific types of ion channel gain- (GoF) or loss-of-function (LoF) characteristics. ASMFG producing FPs (IncrIA/CRDs as a subset of FP/PSWs) have both GoF skeletal muscle voltage-gated sodium (Na+)/potassium (K+) channels and LoF chloride (Cl-) channels. Conversely, myotonic ASMFGs may have LoF Cl-, or GoF Na+ voltage-gated channels, but normal functioning voltage-gated K+ channels. Such unique combinations of ion channel dysfunction directly result in the stereotypical discharge characteristics associated with each particular waveform: FPs and their derivatives being relatively slow and regular, while MyoDs are comparatively more rapid and variable in frequency. Therefore, all of the above-noted ASMFG are in effect channelopathies.

ALSUntangled reviews alternative and off-label treatments for people living with amyotrophic lateral sclerosis (PALS). In this review, we assess the utilization of dietary zinc supplements for modulating ALS pathology and progression. Studies in mouse models of ALS have demonstrated that high-dose zinc supplementation may be harmful, but moderate doses could potentially be beneficial. Clinical data is limited, and only one trial has explored zinc supplementation within PALS. This study reported potential benefits in slowing ALS progression but lacked statistical analyses and failed to report quantitative evidence. Numerous case reports from individual patients at varying doses have demonstrated no benefit. Zinc supplements at moderate doses are generally low cost and not associated with severe complications, but further research is required to determine the safety and efficacy of zinc supplementation within PALS. Therefore, we cannot at this time, endorse zinc supplementation to slow ALS progression.

The electrodiagnostic instrument is foundational to the acquisition of electrophysiologic data and its subsequent interpretation and diagnostic implications. The initiation of data acquisition occurs at the three recording electrodes which consist of: E-1 (the noninverting amplifier port), E-2 (the inverting amplifier port), and E-0 (the so-called ground electrode). All three electrodes are essential in forming the recording montage. They must have similar, high-quality impedance and be properly connected to the amplifier. Their recording surfaces and the tissues from which they record must have low impedance and be properly prepared and applied at the recording site to ensure an accurate representation of the electrophysiologic signal. Both surface and needle electrodes can be used, contingent on the technique and data required (i.e., nerve conduction studies or needle electromyography, respectively). These biologic signals are small, ranging from millivolts to microvolts, depending on the generator source (e.g., muscle and nerve). Therefore, they must be amplified and subsequently filtered. Artifacts, distorted signal amplification, or inappropriate filtration will result in waveform distortion leading to erroneous interpretation (i.e., false positives or negatives). The electrodiagnostic medicine consultant (EMC) has other tools to deal with this, such as averaging. The signal is then digitized and displayed visually and acoustically through an analog-to-digital converter/loudspeaker requiring appropriate amplification and time scale to avoid any signal distortion. The EMC can then visually as well as auditorily analyze the signal of interest and store or print out the data for further interpretation. Current technology in instrumentation permits greater precision and accuracy in data analysis. Failure at any one of the above sequential processing steps can lead to data misinterpretation. It is incumbent upon the EMC to be thoroughly familiar with all of the steps in this process, including potential shortcomings.

Walter Eichler (1904-1942) performed the first in situ nerve conduction studies in humans. Eichler's work has been largely overlooked and there have been no biographical accounts written of him. His 1937 paper, uber die Ableitung der Aktionspotentiale vom menschlichen Nerven in situ (On the recording of the action potentials from human nerves in situ) was translated and reviewed. Archival material was obtained on his career that was housed predominantly at the University of Freiburg im Breisgau. He had memberships in Nazi organizations but did not appear to be politically active. During his brief career, he constructed novel equipment and established seminal principles for performing nerve conductions on humans. The authors repeated his experiment in the ulnar nerve, which duplicated Eichler's findings. His recordings were quite remarkable given advances in technology. In summary, the Eichler paper is the first study in the development of in situ clinical electroneurography in humans. Many of his procedural observations are still fundamental in the current practice of electroneurography. As best can be determined, his study in humans did not appear ethically compromised. Although Eichler's personal background remains open to question, his paper is a seminal study in the history and development of clinical electroneurography.Abbreviations: AP: Action potential; C: Capacitor; CNP: Compound nerve potential; DC: Direct current; E1: Preferred term for active electrode; E2: Preferred term for reference electrode; NSDaB: Nationalsozialistische Deutsche NSD-artzebund (National Socialist German Doctors' League; NSDAP: Nationalsozialistische Deutsche Arbeiterpartei (National Socialist German Workers' Party/ Nazi Party); SS: Schutzstaffel (Protective Echelon or Squad of the Nazi party)

INTRODUCTION/AIMS:In healthy subjects, we observed high amplitude motor unit potential (MUP) waveforms that resembled the cannula potential (CP) with a positive sharp wave (PSW)-like waveform. We analyzed the source of this signal, its prevalence, and its effects on the analysis of electromyographic waveforms. METHODS:Three channel recordings were performed to explore the contribution of the needle core and cannula to the MUP. In 7 control subjects with no neuromuscular disease, the EMG interference pattern was quantified for the amplitude asymmetry (AASM) of its positive and negative going peaks. RESULTS:The large amplitude MUP resembling a CP with a PSW-type waveform is recorded by the needle core, not the cannula. With a slight change in needle position, its amplitude decreased and the waveform had a normal appearance. Thus, it is an artifact. Such potentials (AASM > 150%) are commonly encountered (frequency 7%) and occur in all muscles and subjects in this study. DISCUSSION:The artifact is an enigma and appears related to the interaction between the needle and muscle fiber(s) similar to that in PSW signals. Failure to recognize these waveforms may result in a false impression of abnormality. AASM calculations can help confirm this artifact in automated analysis algorithms to preclude false positive neurogenic patterns.

The compound muscle action potential (CMAP) is among the first recorded waveforms in clinical neurography and one of the most common in clinical use. It is derived from the summated muscle fiber action potentials recorded from a surface electrode overlying the studied muscle following stimulation of the relevant motor nerve fibres innervating the muscle. Surface recorded motor unit potentials (SMUPs) are the fundamental units comprising the CMAP. Because it is considered a basic, if not banal signal, what it represents is often underappreciated. In this review we discuss current concepts in the anatomy and physiology of the CMAP. These have evolved with advances in instrumentation and digitization of signals, affecting its quantitation and measurement.It is important to understand the basic technical and biological factors influencing the CMAP. If these influences are not recognized, then a suboptimal recording may result. The object is to obtain a high quality CMAP recording that is reproducible, whether the study is done for clinical or research purposes.The initial sections cover the relevant CMAP anatomy and physiology, followed by how these principles are applied to CMAP changes in neuromuscular disorders. The concluding section is a brief overview of CMAP research where advances in recording systems and computer-based analysis programs have opened new research applications. One such example is motor unit number estimation (MUNE) that is now being used as a surrogate marker in monitoring chronic neurogenic processes such as motor neuron diseases.

ALSUntangled reviews alternative and off-label treatments on behalf of people with ALS (PALS) who ask about them. Here, we review withania somnifera (WS) commonly known as ashwagandha or winter cherry. WS has plausible mechanisms for slowing ALS progression because of its effects on inflammation, oxidative stress, autophagy, mitochondrial function, and apoptosis. Preclinical trials demonstrate that WS slows disease progression in multiple different animal models of ALS. Of the five individuals we found who described using WS for their ALS, two individuals reported moderate benefit while none reported experiencing any significant side effects. There is currently one clinical trial using WS to treat PALS; the results are not yet published. There are no serious side effects associated with WS and the associated cost of this treatment is low. Based on the above information, WS appears to us to be a good candidate for future ALS trials.

Electrical Interference (EI: radiated electromagnetic and/or power line interference) is a common problem in clinical neurophysiology with many causes and thus various conceivable solutions. Although newer digitized electrodiagnostic (EDX) systems have markedly reduced EI issues, it remains a possible impediment in achieving high quality studies. So that the electrodiagnostic medicine consultant (EMC) can problem solve EI, this monograph details the fundamental functional concepts and terminology of electronic amplification and recording electrodes from a practical perspective. This information is then utilized in a proposed standard operating protocol (SOP) to help the EMC address a wide variety of EI sources. Three major EI sources are considered: the EDX system/operator error, the environment, and the patient. The first is a thorough assessment of the recording electrodes from the perspective of clean electrodes, security of attachment, appropriate gel application, proper lead connections to both the patient and instrument, and similarity of electrode composition. Second is how adverse environmental conditions are mitigated through isolating the EDX instrument from nearby large generator sources, unplugging unnecessary equipment, keeping the amplifier close to the patient along with short and braided electrode leads, and utilize filtering (both 60 Hz and total bandwidth) with appropriate caution to avoid unwanted signal distortion. Third, the patient and EMC interaction must be considered. Specifically, all electronic devices that can be removed should be powered down and relocated as far as feasible from the EDX system, including digital watches, cell phones, TENS units, and other such devices. A systematic application of the above proposed protocol should solve the majority of EI issues.

ALSUntangled reviews alternate and off-label treatments prompted by patient interest. Here, we review psilocybin, a chemical derived from mushrooms and belonging in the category of drugs known as psychedelics. Psilocybin has plausible mechanisms for slowing ALS progression because of its ability to cross the blood brain barrier and effect neurogenesis and inflammation. Currently, there are no pre-clinical ALS models, case reports, or trials for psilocybin and ALS in the context of disease modifying therapy. Depending on dosing, there can be a high risk of psychological side effects including hallucinations and physical harm. Based on the above information, we do not currently support the use of psilocybin as a means to slow ALS progression.

Spurred by patient interest, ALSUntangled herein examines the potential of the Portable Neuromodulation Stimulator (PoNS™) in treating amyotrophic lateral sclerosis (ALS). The PoNS™ device, FDA-approved for the treatment of gait deficits in adult patients with multiple sclerosis, utilizes translingual neurostimulation to stimulate trigeminal and facial nerves via the tongue, aiming to induce neuroplastic changes. While there are early, promising data for PoNS treatment to improve gait and balance in multiple sclerosis, stroke, and traumatic brain injury, no pre-clinical or clinical studies have been performed in ALS. Although reasonably safe, high costs and prescription requirements will limit PoNS accessibility. At this time, due to the lack of ALS-relevant data, we cannot endorse the use of PoNS as an ALS treatment.

BACKGROUND:In motor nerve conduction studies (MNCS), proximal stimulation should give a longer duration and lower amplitude compound muscle action potential (CMAP) due to higher temporal dispersion. Yet the CMAP waveforms at the distal and proximal stimulation sites appear remarkably similar. The objective of this study was to confirm this anomaly and investigate its possible cause by studying the median and ulnar nerves. METHODS:Recordings from 50 subjects with normal electrodiagnostic studies were reviewed. The conduction velocity (CV) was measured using different points on the negative phase of the CMAP including its peak and baseline crossing. Collision studies were performed in three healthy subjects to measure the dispersion when nerve action potentials (APs) propagated from elbow to wrist. RESULTS:CV was relatively unaffected by the measurement point on the CMAP. The CMAP duration with elbow stimulation increased minimally compared to wrist stimulation. This was inconsistent with the dispersion of the AP from wrist to elbow measured in collision studies. DISCUSSION:The insignificant change in the CMAP in spite of axon AP dispersion is an enigma. We hypothesize that the terminal conduction time (TCT) (i.e., conduction in terminal axon branches, neuromuscular transmission, etc.) is independent of axon CV, represents a significant portion of the latency, masks AP dispersion, and reduces CMAP dispersion. This yields similar CMAPs with distal and proximal stimulation. The onset latency at the distal stimulation site does not depend on CV. Thus, onset latency and CV may not reflect the conduction properties of the fastest conducting axons.

INTRODUCTION/AIMS:Conventional F wave analysis involves a relatively uniform physiological environment induced by supramaximal stimulations. The F wave characteristics in a dynamic physiological condition, however, are rarely investigated. This study aimed to improve understanding of F wave properties in the more dynamic process by introducing a novel method to analyze F waves based on the compound muscle action potential (CMAP) scan technique. METHODS:Twenty four healthy subjects participated in the study. The CMAP scan was applied to record muscle responses in the abductor pollicis brevis (APB) and abductor digiti minimi (ADM) muscles, respectively. F wave characteristics including mean F wave amplitude and latency (F-M latency), persistence and activating threshold were quantified. RESULTS:An average of 200 F waves per muscle were obtained from the CMAP scan recording. Weak to moderate correlations between F wave amplitude and stimulating intensity were observed in most of the APB (19 muscles; r = 0.33 ± 0.14, all p < .05) and ADM (23 muscles, r = 0.46 ± 0.16, all p < .05) muscles. Significantly longer mean F latency and lower activating F-threshold were found in the ADM muscles (F-M latency: APB: 25.43 ± 2.39 ms, ADM: 26.15 ± 2.32 ms, p < .05; F-threshold: APB: 7.68 ± 8.96% CMAP, ADM: 2.35 ± 2.42% CMAP, p < .05). DISCUSSION:This study introduces new features of F waves using the CMAP scan technique and identifies differences of F wave characteristics between the hand muscles. The CMAP scan based F waves analysis can be combined with the motor unit number estimation to assess functional alterations in motor neurons in neurological disorders.

The extracellular waveform manifestations of the intracellular action potential are the quintessential diagnostic foundation of electrodiagnostic medicine, and clinical neurophysiology in general. Volume conduction is the extracellular current flow and associated voltage distributions in an ionic conducting media, such as occurs in the human body. Both surface and intramuscular electrodes, in association with contemporary digital electromyographic systems, permit very sensitive detection and visualization of this extracellular spontaneous, voluntary, and evoked nerve/muscle electrical activity. Waveform configuration, with its associated discharge rate/rhythm, permits the identification of normal and abnormal waveforms, thereby assisting in the diagnosis of nerve and muscle pathology. This monograph utilizes a simple model to explain the various waveforms that may be encountered. There are a limited number of waveforms capable of being generated in excitable tissues which conform to well‐known volume conductor concepts. Using these principles, such waveforms can be quickly identified in real time during clinical studies.

ALSUntangled reviews alternative and off-label treatments for people with amyotrophic lateral sclerosis (PALS). Here we review glucocorticoids. Neuroinflammation plays a prominent role in amyotrophic lateral sclerosis (ALS) pathogenesis, so some hypothesize that glucocorticoids might be an effective ALS therapy through their immunosuppressive effects. In this paper, we review the available evidence for glucocorticoids in ALS, including one pre-clinical study with a genetic mouse model of ALS, nine case reports (ranging from 1 to 26 patients each), and four clinical trials. We also review the possible side effects (including steroid myopathy) and the costs of therapy. We graded the level of evidence as follows: Mechanism, D; Pre-Clinical, F; Cases, B; Trials, F; Risks, C. Our review of the current evidence concludes that glucocorticoids do not offer clinical benefit in ALS and confer serious risks. Thus, ALSUntangled does not recommend glucocorticoids as a treatment for ALS.

ALSUntangled reviews alternative and off-label treatments for people living with amyotrophic lateral sclerosis (PALS). Here we review insulin, which has at least one plausible mechanism for slowing ALS progression. However, pre-clinical studies are limited and there have been no trials in PALS yet. Insulin use in patients without a metabolic need may cause very serious and potentially lethal side effects. While further studies to evaluate potential benefits may be warranted, at this time we cannot endorse insulin treatment to slow ALS progression.