Ellen M. Maathuis

Guillain–Barré syndrome subtypes related to Campylobacter infection

Background In Guillain–Barré syndrome (GBS), the diversity in electrophysiological subtypes is unexplained but may be determined by geographical factors and preceding infections. Acute motor axonal neuropathy (AMAN) is a frequent GBS variant in Japan and one study proposed that in Japan, Campylobacter jejuni infections exclusively elicit AMAN. In The Netherlands C jejuni is the predominant type of preceding infection yet AMAN is rare. This may indicate that not all Dutch GBS patients with C jejuni infections have AMAN. Objective To determine if GBS patients with a preceding C jejuni infection in The Netherlands exclusively have AMAN. Methods Retrospective analysis of preceding infections in relation to serial electrophysiology and clinical data from 123 GBS patients. C jejuni related cases were defined as having preceding diarrhoea and positive C jejuni serology. Electrophysiological characteristics in C jejuni related cases were compared with those in viral related GBS patients. In addition, eight GBS patients from another cohort with positive stool cultures for C jejuni were analysed. Results 17 (14%) of 123 patients had C jejuni related GBS. C jejuni patients had lower motor and higher sensory action potentials compared with viral related cases. Nine (53%) C jejuni patients had either AMAN or inexcitable nerves. However, three (18%) patients fulfilled the criteria for acute inflammatory demyelinating polyneuropathy (AIDP). Also, two (25%) of eight additional patients with a C jejuni positive stool sample had AIDP. Conclusion In The Netherlands, C jejuni infections are strongly, but not exclusively, associated with axonal GBS. Some patients with these infections fulfil current criteria for demyelination.

The electrophysiological muscle scan.

This study aims to assess the potential of the electrophysiological muscle scan or stimulus–response curve as a diagnostic instrument. If stimulus intensity is gradually increased from subthreshold to supramaximal values, all motor units in a muscle are successively activated. Thus, by plotting response size versus stimulus intensity, an impression (scan) of the entire muscle can be obtained. We recorded 54 detailed scans from 34 patients and 11 healthy subjects, and analyzed them visually and quantitatively. The scan summarized much diagnostic information in a single picture. Specific patterns in or properties of the scan (steps, maximum, variability, decrements, stimulus intensities used) provide clinically relevant information regarding motor unit number, size, and stability, and neuromuscular transmission and axonal excitability. The scan can be recorded noninvasively in about 5 minutes and is fairly easy to interpret. Because it is built up from contributions of all functioning motor units, the scan shows if and how many large motor units are present. There is no sample bias. For these reasons, further exploration and exploitation of this tool in the clinical setting are warranted. Muscle Nerve, 2007

Motor unit tracking with high-density surface EMG

Following (tracking) individual motor units over time can provide important new insights, both into the relationships among various motor unit (MU) morphological and functional properties and into how these properties are influenced by neuromuscular disorders or interventions. The present study aimed to determine whether high-density surface EMG (HD-sEMG) recordings, which use an array of surface electrodes over a muscle, can increase the yield of MU tracking studies in terms of the number of MUs that can be tracked. For that purpose, four HD-sEMG recording sessions were performed on the thenar muscles of ten healthy subjects. Decomposition of the recorded composite responses yielded a study total of 2849 motor unit action potentials (MUAPs). MUAPs that were found in both of the first two sessions, performed on the same day, were defined as trackable MUAPs. Our results show that 22 (median value; range, 13-34) MUAPs per nerve were trackable, which represented approximately 5% of the total MU population. Of these trackable MUAPs, 16 (11-26) could also be found in one or both of the third and fourth sessions, which were performed between 1 and 13 weeks after the initial studies. Nine (4-18) MUAPs were found in all four sessions. Many of the characteristic MUAP shapes matched well between sessions, even when these sessions were several weeks apart. However, some MUAPs seem very sensitive to changes in arm position or in the muscles morphology (e.g., to changes in muscle fiber length due to variable degrees of thumb flexion or extension), particularly those from larger and/or superficial MUs. Standardization is, therefore, essential to detect even small MUAP changes, as may occur with pathology or interventions. If this is accomplished, MU tracking with HD-sEMG may prove to be a powerful tool for a promising type of neurophysiological investigation.

Residual fatigue in Guillain-Barré syndrome is related to axonal loss

Objective: To determine the occurrence of residual loss of peripheral nerve axons by motor unit number estimation (MUNE) and conventional nerve conduction studies (NCS) in patients with and without severe fatigue. Methods: Thirty-nine patients at a median of 8 years (range 1–23 years) after diagnosis of Guillain-Barré syndrome were neurologically examined and divided in 2 subgroups based on the presence of severe fatigue (defined as a fatigue severity score ≥5). All patients were investigated with standard NCS and MUNE. Normal values for MUNE were collected in 14 healthy controls. Results: MUNE of the thenar muscles was lower in the 15 patients with severe fatigue (median 125, interquartile range 65–141) compared with the 24 patients without severe fatigue (median 258, interquartile range 120–345) (p = 0.002). In the healthy controls, MUNE was 358 (245–416). Severe fatigue was also related to lower sensory nerve action potential amplitude of the median (p = 0.01) and ulnar nerve (p = 0.03). The 2 subgroups did not differ regarding neurologic deficits, disability, and the remaining conventional motor NCS. Conclusion: This study demonstrates that severe fatigue after Guillain-Barré syndrome is related to more pronounced axonal loss, represented by lower MUNEs and lower sensory nerve action potentials.

Reproducibility of the CMAP scan

INTRODUCTIONnThe CMAP scan is a surface EMG method based on the successive activation of motor units. It provides information about reinnervation processes, the number of functional motor units and nerve excitability. The CMAP scan has potential value as a follow-up tool in monitoring disease progression, recovery or aging of the peripheral nerves. In this study, we assessed its interobserver and different-day reproducibility.nnnMETHODSnTwo investigators recorded CMAP scans in ten healthy subjects, each on two different days. Intraclass correlation coefficients (ICCs) and coefficients of variation (CoVs) were calculated for the parameters extracted from the CMAP scan.nnnRESULTSnAll CMAP scan parameters had a good different day (ICCs >0.8 and CoVs <15%) and interobserver reproducibility (ICCs >0.7 and CoVs ≤ 15%). Different-day reproducibility was better than interobserver reproducibility.nnnCONCLUSIONnCMAP scan test-retest variability is small, suggesting that as a follow-up tool it may be sensitive to fairly small (patho)physiological changes in the studied variables.

The CMAP scan as a tool to monitor disease progression in ALS and PMA

Abstract Amyotrophic lateral sclerosis (ALS) and progressive muscular atrophy (PMA) are characterized by a loss of motor units (MUs), reinnervation and, eventually, muscle fibre loss. These three aspects are all reflected in the compound muscle action potential scan (CMAP scan, a high-detail stimulus response curve), which visualizes large MU potentials as ‘steps’. We explored changes in the CMAP scan over time, combined the information on steps and CMAP amplitude into a CMAP scan-based progression score (CSPS), and correlated this score with motor unit number estimates (MUNE). Ten patients (three PMA, seven ALS; age 37−77 years) were included. CMAP scan and MUNE measurements were performed five times during a three-month period. Nine patients had additional measurements. The follow-up period was 3−24 months. Results demonstrated that abnormalities in steps preceded a decline in maximum CMAP amplitude during follow-up. Usually, both steps and maximum CMAP amplitude changed between recordings. The correlation between the CSPS and MUNE was −0.80 (p < 0.01). In conclusion, the CMAP scan can be used to visualize and quantify disease progression in a muscle affected by MND. The CSPS is a measure of MU loss that is quick and easy to obtain and that, in contrast to MUNE, has no sample bias.

Optimal stimulation settings for CMAP scan registrations

Background The CMAP (Compound Muscle Action Potential) scan is a non-invasive electrodiagnostic tool, which provides a quick and visual assessment of motor unit potentials as electrophysiological components that together constitute the CMAP. The CMAP scan records the electrical activity of the muscle (CMAP) in response to transcutaneous stimulation of the motor nerve with gradual changes in stimulus intensity. Large MUs, including those that result from collateral reinnervation, appear in the CMAP scan as so-called steps, i.e., clearly visible jumps in CMAP amplitude. The CMAP scan also provides information on nerve excitability. This study aims to evaluate the influence of the stimulation protocol used on the CMAP scan and its quantification. Methods The stimulus frequency (1, 2 and 3 Hz), duration (0.05, 0.1 and 0.3 ms), or number (300, 500 and 1000 stimuli) in CMAP scans of 23 subjects was systematically varied while the other two parameters were kept constant. Pain was measured by means of a visual analogue scale (VAS). Non-parametric paired tests were used to assess significant differences in excitability and step variables and VAS scores between the different stimulus parameter settings. Results We found no effect of stimulus frequency on CMAP scan variables or VAS scores. Stimulus duration affected excitability variables significantly, with higher stimulus intensity values for shorter stimulus durations. Step variables showed a clear trend towards increasing values with decreasing stimulus number. Conclusions A protocol delivering 500 stimuli at a frequency of 2 Hz with a 0.1 ms pulse duration optimized CMAP scan quantification with a minimum of subject discomfort, artefact and duration of the recording. CMAP scan variables were influenced by stimulus duration and number; hence, these need to be standardized in future studies.

Size does matter: The influence of motor unit potential size on statistical motor unit number estimates in healthy subjects

OBJECTIVEnThe statistical method of motor unit number estimation (MUNE) assumes that all motor unit potentials (MUPs) have the same size. The present study aims to evaluate the consequences of this assumption as well as its implications for the validity of statistical MUNEs.nnnMETHODSnWe performed statistical and multiple point stimulation (MPS) MUNE with an array of 120 electrodes on the thenar muscles of 15 healthy subjects. These recordings allow isolation and quantification of the effect of non-uniform MUP size on MUNE, because the differences in submaximal CMAP size (and, hence, in MUNE) between electrodes are due almost entirely to differences in (summed) MUP size.nnnRESULTSnWe found no correlation between statistical and MPS MUNEs. Statistical MUNEs proved very sensitive to small variations in the bandwidth (variance) of the response series; MUNEs from electrodes only 8mm apart could deviate by as much as 60%. This variation in bandwidth resulted from spatial (and, hence, size) differences between the contributing MUPs.nnnCONCLUSIONSnStatistical MUNEs are very sensitive to violation of the uniform MUP-size assumption, to an extent that blurs any correlation with MPS MUNE in healthy subjects.nnnSIGNIFICANCEnStatistical MUNE cannot be used to detect mild to moderate motor unit losses.

CMAP scan discontinuities: automated detection and relation to motor unit loss.

UNLABELLEDnObjective To evaluate an automated method that extracts motor unit (MU) information from the CMAP scan, a high-detail stimulus-response curve recorded with surface EMG. Discontinuities in the CMAP scan are hypothesized to result from MU loss and reinnervation.nnnMETHODSnWe introduce the parameter D50 to quantify CMAP scan discontinuities. D50 was compared with a previously developed manual score in 253 CMAP scans and with a simultaneously obtained motor unit number estimate (MUNE) in 173 CMAP scans. The effect of MU loss on D50 was determined with a simulation model.nnnRESULTSnWe found a high agreement (sensitivity=86.8%, specificity=96.6%) between D50 and the manual score. D50 and MUNE were significantly correlated below 80 MUs (r=0.65, n=68, p<0.001), but not when MUNE was larger than 120 MUs (r=0.23, n=59, p=0.08).nnnCONCLUSIONSnDiscontinuities in the CMAP scan as expressed by a decreased D50 are related to significant MU loss. The determination of D50 is objective, quantitative, and less time-consuming than both manual scoring and many existing MUNE methods.nnnSIGNIFICANCEnD50 is potentially useful to monitor neurogenic disorders and moderate to severe MU loss.

Limb motor nerve dysfunction in Miller Fisher syndrome

Typical Miller Fisher syndrome (MFS) lacks limb muscle weakness, but some patients may unpredictably progress to severe Guillain‐Barré syndrome. The compound muscle action potential (CMAP) scan is a recently developed non‐invasive, painless, and reproducible method for detecting early changes in motor nerve excitability. This technique was used to monitor subclinical limb motor nerve dysfunction during disease course in typical MFS. Three Miller Fisher patients with preserved limb muscle strength and normal routine nerve conduction studies were included. Frequent serial CMAP scanning of the median nerve was performed during acute phase and follow‐up and was related to clinical course and outcome. All patients showed an abnormal increase in the range of stimulus intensities at the day of hospital admission, indicating reduced motor nerve excitability already at the earliest stage of disease. Median nerve dysfunction progressed in parallel or even before clinical deterioration, and improved with clinical recovery. Our study shows that typical MFS is a more general neuropathy, affecting peripheral motor nerves even in patients with preserved limb strength and conduction velocity. CMAP scanning is a sensitive technique for early detection of subclinical motor nerve dysfunction and for monitoring disease activity in immune‐mediated neuropathies.