F wave analysis based on the compound muscle action potential scan.

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.

Defective E2 electrode lead gives low-amplitude compound muscle action potential.

INTRODUCTION/AIMS: Low-amplitude compound muscle action potential (CMAP) suggests a neuromuscular pathology. Low amplitude will also result from a defective E1 electrode or its lead, that is, a technical artifact. The aim of this study was to investigate the effect of a defective E2 electrode lead on the CMAP. METHODS: The CMAP was recorded using standard nerve conduction methodology and all electrode leads connected properly. Signals were then recorded when either the E1 or the E2 electrode lead was disconnected from the amplifier. This simulated a defective electrode lead. Studies were performed in four nerves of a healthy subject. RESULTS: CMAP amplitude was reduced as expected when E1 was disconnected. Surprisingly, the amplitude fell by more than 65% when the E2 lead was disconnected, although E1 was properly connected. DISCUSSION: E1 and E2 electrodes contribute to the CMAP. A defective recording electrode lead to E1 or E2 results in a low-amplitude CMAP. The amplitude drop observed with a disconnected E2 lead was far greater than the signal recorded by the E2 electrode. This occurs due to the amplifier's inherent property to reduce the voltage difference between the E1 and E2 inputs. When E2 lead is defective, the CMAP will be an attenuated version of the signal recorded by the E1 electrode, and vice versa. When low-amplitude CMAP amplitude is observed in all conduction studies, technical artifact should be considered before exploring the pathological basis for the abnormal results.

Recording sensory nerve action potential using different electrode types.

INTRODUCTION/AIMS: Switching between different types of electrodes during motor and sensory nerve conduction studies adds time to a study. We investigated the use of disposable disc electrodes (DDE) used for motor nerve conduction studies to record the antidromic sensory nerve action potential (SNAP) in median, ulnar and radial sensory nerve conduction studies. METHODS: The SNAP was recorded using four different electrode types: reusable ring, reusable bar, disposable ring, and DDE in a random rotating order. Studies were performed in healthy subjects. Other than being an adult with no history of neuromuscular disease, there were no exclusion criteria. RESULTS: We studied 20 subjects (11 females, 9 males; age 41.1 ± 15.7 y). The SNAP waveforms recorded by all four electrode types were similar. There was no statistically significant difference in the onset latency, peak latency (PL), negative peak amplitude (NPA), peak to peak amplitude, or conduction velocity. In individual nerve recordings, the absolute PL difference between reusable ring electrodes (our current standard) and DDE was less than 0.2 ms in 58 of 60 (97%) nerves. The mean absolute NPA difference was 3.1 µV (standard deviation = 2.85 µV). Recordings with NPA difference >5 µV also had high NPA and/or had large artifacts. DISCUSSION: DDE may be used for performing motor and sensory nerve conduction studies. This can reduce the time required for electrodiagnostic testing.

Volume conduction: Extracellular waveform generation in theory and practice.

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.

Serial electrodiagnostic studies in acute partial conduction block from cyclist's palsy.

INTRODUCTION/AIMS: To date, there is minimal literature in following resolution of partial conduction block (PCB) in compression neuropathy. We investigated a case of cyclist's palsy with PCB from compression using serial nerve conduction studies to monitor recovery. METHODS: Clinical recovery was monitored concomitant with compound muscle action potential (CMAP) amplitudes that were recorded from 3 ulnar-innervated muscles (first dorsal interosseous [FDI] 6 days post-onset, palmar interosseus [PI] 16 days post-onset, and abductor digiti minimi [ADM]) in both limbs. Sensory nerve conduction studies and needle electromyography were also performed. RESULTS: PCB was demonstrated in the FDI and PI with recordings done proximal and distal to the site of injury. Recovery in the FDI and PI occurred between week 2 and 3 post-onset but continued to improve until about 14 wk post-onset when the CMAP values on the affected side approximated the contralateral side. Sensory conduction studies were normal and symmetric. Needle EMG at 21 days post-injury showed no active denervation and a reduced number of normal-appearing motor unit potentials firing >16 Hz that reverted to a normal pattern on final study at 99 days post-onset. DISCUSSION: This study shows how rapidly PCB may initially resolve although full recovery takes longer. Criteria for defining PCB may be misleading when doing nerve conductions and comparing only the evoked responses below and above the block. To fully characterize PCB, it is important to optimize the position of the active recording electrode (E1) as well as compare results with the unaffected side.

Motor unit recruitment and firing rate at low force of contraction.

INTRODUCTION/AIMS: A prevailing concept of motor unit (MU) recruitment used for calculating recruitment ratio (RR) suggests a progressive linear increase in firing rate (FR). The objective of this study is to assess its validity. METHODS: Concentric needle electromyography (EMG) recordings were made in normal muscle and abnormal muscle of patients with neurogenic findings. Signals recorded at low force were visually decomposed to study MU FR at onset, recruitment of a second MU, and recruitment of more MUs with further increases in force. RESULTS: We observed one to six MUs discharging at a rate < 15 Hz in normal muscles at low force. The MU FR was 5-8 Hz at onset. With increasing force, FR increased by 3-5 Hz and then idled at <15 Hz while other MUs were recruited. The recruitment frequency (RF) and RR had low sensitivity and were abnormal mainly in moderately to severely weak muscles. DISCUSSION: Our data are consistent with FR analysis results described by other investigators. It does not support a progressive linear increase in MU FR with recruitment. A revised model for MU recruitment at low effort during gradual increase in force is presented. On subjective assessment, the FR of the fastest firing MU can help detect MU loss in neurogenic processes.

Reinnervation as measured by the motor unit size index is associated with preservation of muscle strength in amyotrophic lateral sclerosis, but not all muscles reinnervate.

INTRODUCTION/AIMS: The motor unit size index (MUSIX) may provide insight into reinnervation patterns in diseases such as amyotrophic lateral sclerosis (ALS). However, it is not known whether MUSIX detects clinically relevant changes in reinnervation, or if all muscles manifest changes in MUSIX in response to reinnervation after motor unit loss. METHODS: Fifty-seven patients with ALS were assessed at 3-month intervals for 12 months in four centers. Muscles examined were abductor pollicis brevis, abductor digiti minimi, biceps brachii, and tibialis anterior. Results were split into two groups: muscles with increases in MUSIX and those without increases. Longitudinal changes in MUSIX, motor unit number index (MUNIX), compound muscle action potential amplitude, and Medical Research Council strength score were investigated. RESULTS: One hundred thirty-three muscles were examined. Fifty-nine percent of the muscles exhibited an increase in MUSIX during the study. Muscles with MUSIX increases lost more motor units (58% decline in MUNIX at 12 months, P < .001) than muscles that did not increase MUSIX (34.6% decline in MUNIX at 12 months, P < .001). However, longitudinal changes in muscle strength were similar. When motor unit loss was similar, the absence of a MUSIX increase was associated with a significantly greater loss of muscle strength (P = .002). DISCUSSION: MUSIX increases are associated with greater motor unit loss but relative preservation of muscle strength. Thus, MUSIX appears to be measuring a clinically relevant response that can provide a quantitative outcome measure of reinnervation in clinical trials. Furthermore, MUSIX suggests that reinnervation may play a major role in determining the progression of weakness.

Atypical fibrillation and fasciculation potentials: An exercise in waveform identification and analysis.

No consensus criteria exist for recording and analyzing waveforms in clinical electromyography (EMG). There have been significant technical improvements in recent decades that are under-used in both routine practice and research. In current practice, disciplined techniques in acquisition and analysis of signals are required to appropriately define them. As an example, we describe such an exercise in acquisition and analysis. During a routine study, atypical spontaneous activity was encountered. High-quality digital recordings were stored for off-line analysis. These revealed waveforms that could be isolated and quantitatively defined using basic instrumentation available on most modern EMG systems: "slow" firing fibrillation potentials and a repeating fasciculation potential. Subjective analysis alone could not have identified them. To improve accuracy in identification and understanding of these waveforms, we propose criteria for data collection and signal analysis. This is critical for quality in routine practice, education, and proper reporting of electrophysiological signals.

Experiment for teaching virtual cathode in nerve conduction studies.

INTRODUCTION/AIMS: The virtual cathode (VC) is a site near the anode where the nerve can be stimulated. Costimulation of neighboring nerves via the VC can affect recording and interpretation of responses. Hence, it is important to teach trainees the concept of the VC. The VC has been demonstrated previously with subtle changes in response latency, amplitude, and shape. Herein we describe an experiment that simply demonstrates a VC with its effects recognizable by gross changes in waveforms. METHODS: Compound muscle action potentials of the abductor pollicis brevis were recorded using various placements of the cathode and anode at different stimulus intensity levels. Studies were performed in nine healthy subjects. RESULTS: Three patterns were observed that demonstrated no stimulation, partial stimulation, and complete nerve stimulation by the VC. Partial stimulation yielded responses with long duration and low amplitude. Response patterns also depended on stimulus strength and proximity of the nerve from the skin surface. DISCUSSION: This experiment demonstrates that nerve stimulation can occur near the anode when high-intensity stimulus is used. It also illustrates collision of action potentials. This exercise can help trainees understand potential pitfalls in nerve conduction studies, especially at very proximal stimulation sites or when high stimulus intensity is used.

MeRef: Multivariable extrapolated reference values in motor nerve conduction studies.

INTRODUCTION: In this study we describe a method called "multivariable extrapolated reference values" (MeRef) that derives reference values (RVs) using patient data and includes the dependence of these variables on multiple patient demographic variables, such as age and height. METHODS: Computer simulations were used to generate "normal" and "patient" nerve conduction data. Median, ulnar, and tibial motor nerve conduction data from 500 patients studied were tabulated. Data were analyzed using the MeRef method. RESULTS: The simulations showed great similarity between RVs obtained from MeRef of "patient" data and traditional analysis of "normal" data. In the real patient data, MeRef gave RVs as regression equations based on patient age and/or height. DISCUSSION: MeRef can provide RVs by including patient demographic data and does not require subject grouping. It provides parameters of multivariable linear regression and standard deviation, and requires a few hundred patient studies to define reference values.

Form factor analysis of the surface electromyographic interference pattern.

INTRODUCTION: In contrast to needle electromyography (EMG), surface EMG recordings are painless. It is of interest to develop methods to analyze surface EMG for diagnostic purposes. METHODS: Surface EMG interference pattern (SIP) recordings from the abductor pollicis brevis muscle of healthy subjects and subjects with amyotrophic lateral sclerosis (ALS) were analyzed by measuring root-mean-square (RMS) voltage, mean rectified voltage, form factor (FF), and the clustering index (CI). The FF vs SIP area plot was used for analysis. RESULTS: The SIP FF was increased and abnormal in ALS subjects, especially when SIP area was less than 200 mVms. Power regression showed a faster FF decline with SIP area in ALS patients than in healthy subjects. The CI and FF showed a strong correlation. DISCUSSION: FF is easy to calculate and demonstrates abnormalities in ALS patients.

Motor unit number index: Guidelines for recording signals and their analysis.

INTRODUCTION: This study proposes guidelines for motor unit number index (MUNIX) recording and analysis. METHODS: MUNIX was measured in control participants and in patients with amyotrophic lateral sclerosis. Changes in MUNIX values due to E1 electrode position, number of surface electromyography interference pattern (SIP) epochs, SIP epoch duration, force of contraction, and outlier data points were investigated. RESULTS: MUNIX depends on optimized compound muscle action potential (CMAP) amplitude. Individual muscles showed variations when the number of epochs was low or when the SIP duration was short. Longer SIP duration allowed better recognition of artifacts. MUNIX results were affected by SIP values at all force levels but was more affected when SIP area was low. DISCUSSION: We recommend changing the E1 electrode position to maximize CMAP amplitude. Twenty or more SIP signals of 500-ms duration should be recorded by using force levels ranging from slight to maximum. Traces should be reviewed to identify and exclude signals with tremor or solitary spikes. Muscle Nerve 58: 374-380, 2018.

The extrapolated reference values procedure: Theory, algorithm, and results in patients and control subjects.

INTRODUCTION: Reference values (RVs) are required to separate normal from abnormal values obtained in electrodiagnostic (EDx) testing. However, it is frequently impractical to perform studies on control subjects to obtain RVs. The Extrapolated Reference Values (E-Ref) procedure extracts RVs from data obtained during clinically indicated EDx testing. We compared the E-Ref results with established RVs in several sets of EDx data. METHODS: The mathematical basis for E-Ref was explored to develop an algorithm for the E-Ref procedure. To test the validity of this algorithm, it was applied to simulated and real jitter measurements from control subjects and patients with myasthenia gravis, and to nerve conduction studies from patients with various conditions referred for EDx studies. RESULTS: There was good concordance between E-Ref and RVs for all evaluated data sets. DISCUSSION: E-Ref is a promising method to develop RVs. Muscle Nerve 57: 90-95, 2018.

Tracking motor neuron loss in a set of six muscles in amyotrophic lateral sclerosis using the Motor Unit Number Index (MUNIX): a 15-month longitudinal multicentre trial.

BACKGROUND: Motor Unit Number Index (MUNIX) is a novel neurophysiological measure that provides an index of the number of functional lower motor neurons in a given muscle. So far its performance across centres in patients with amyotrophic lateral sclerosis (ALS) has not been investigated. OBJECTIVE: To perform longitudinal MUNIX recordings in a set of muscles in a multicentre setting in order to evaluate its value as a marker of disease progression. METHODS: Three centres applied MUNIX in 51 ALS patients over 15 months. Six different muscles (abductor pollicis brevis, abductor digiti minimi, biceps brachii, tibialis anterior, extensor dig. brevis, abductor hallucis) were measured every 3 months on the less affected side. The decline between MUNIX and ALSFRS-R was compared. RESULTS: 31 participants reached month 12. For all participants, ALSFRS-R declined at a rate of 2.3%/month. Using the total score of all muscles, MUNIX declined significantly faster by 3.2%/month (p ≤ 0.02). MUNIX in individual muscles declined between 2.4% and 4.2%, which differed from ASLFRS-R decline starting from month 3 (p ≤ 0.05 to 0.002). Subgroups with bulbar, lower and upper limb onset showed different decline rates of ALSFRS-R between 1.9% and 2.8%/month, while MUNIX total scores showed similar decline rates over all subgroups. Mean intraclass correlation coefficient for MUNIX intra-rater reliability was 0.89 and for inter-rater reliability 0.80. CONCLUSION: MUNIX is a reliable electrophysiological biomarker to track lower motor neuron loss in ALS.

Tibial nerve F-wave recordings.

INTRODUCTION: Tibial F-wave recordings are remarkable for their complexity and persistence. We postulate that the signal recorded by the E2 (reference) electrode causes this pattern. METHODS: Tibial F-wave recordings were made from the abductor hallucis (AH) muscle using the standard montage in 10 subjects. Additional far-field simultaneous F-wave recordings were made from the AH, the base of the large toe, and the base of the small toe with the E2 placed on the contralateral foot. RESULTS: F-wave recordings made in the standard manner and from the base of the large or small toes showed complex waveforms and similar latencies. Recordings made from the AH-contralateral foot had simple waveforms in most subjects; in 2 subjects the latencies were longer, and 1 showed reduced persistence. CONCLUSIONS: The tibial F-waves are composed primarily of volume conducted recordings of the tibial-innervated foot muscles from the E2 electrode.

Walter Eichler and his role in the development of electroneurography.

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, Über 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; NSDÄB: Nationalsozialistische Deutsche NSD-Ärtzebund (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).

Revisiting the compound muscle action potential (CMAP).

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.

Deep brain stimulator artifact in needle electromyography: effects and distribution in paraspinal and upper limb muscle.

INTRODUCTION: Deep brain stimulators (DBS) have become a more widespread treatment option for individuals with centrally mediated movement disorders. Such devices are expected to create artifact in standard needle electromyographic (EMG) recordings. METHODS: Five subjects with DBS were studied with standard concentric needle electrode EMG in paraspinal and upper limb muscles. RESULTS: All subjects showed EMG artifact directly related to, and corresponding with, the DBS unit settings. The artifact was very prominent in all paraspinal muscles, although the amplitude was less in lumbar compared with cervical levels. With a large ground electrode next to the insertion site, the artifact was sufficiently small to allow standard EMG examination of upper limb muscles. CONCLUSIONS: The DBS artifact is so prominent in paraspinal muscles that it will not allow standard EMG examination for diagnostic purposes such as radiculopathy. The artifact itself can easily be distinguished from pathological insertional and spontaneous activity.

Changes in tongue pressure, pulmonary function, and salivary flow in patients with amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease involving nerve cells that control voluntary muscle movement (Rowland LP, Shneider NA, N Engl J Med 344(22):1688-1700, 2001). The aim of this study were to determine the pattern of neurodegenerative change in (1) isometric tongue strength (ITS) and spontaneous saliva swallow (SSS) pressure, (2) saliva weight, and (3) forced vital capacity (FVC) in patients with ALS who present with primary spinal versus primary bulbar symptoms. Twenty-three consecutive patients (age = 48-80 years, mean = 59.5 years) were enrolled. Data were collected over three visits (12-week interval) for each group: 9 patients with bulbar symptoms and 14 with spinal symptoms. A significant difference was noted in SSS and ITS in the group with bulbar symptoms from Trial 1 to II and from Trial II to III. SSS and ITS showed a significant difference when comparing Trial I to III but not when comparing Trial I to II for the spinal symptom group, indicating that this group experienced a slower decline in SSS. Saliva production did not show a significant change in the bulbar symptom group but did in the spinal group. FVC was significantly different when comparing Trial I to III and Trial II to III for both groups. FVC, SSS, and ITS may be complimentary measures used as a gauge of an ALS patient's ability to efficiently take oral nutrition and to support required alterations in diet consistency.