Changes in motor nerve excitability in acute phase Guillain-Barré syndrome.

BACKGROUND: The most common subtypes of Guillain-Barré syndrome (GBS) are acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). In the first days after the onset of weakness, standard nerve conduction studies (NCS) may not distinguish GBS subtypes. Reduced nerve excitability may be an early symptom of nerve dysfunction, which can be determined with the compound muscle action potential (CMAP) scan. The aim of this study was to explore whether early changes in motor nerve excitability in GBS patients are related to various subtypes. METHODS: Prospective case-control study in 19 GBS patients from The Netherlands and 22 from Bangladesh. CMAP scans were performed within 2 days of hospital admission and NCS 7-14 days after onset of weakness. CMAP scans were also performed in age- and country-matched controls. RESULTS: CMAP scan patterns of patients who were classified as AMAN were distinctly different compared to the CMAP scan patterns of the patients who were classified as AIDP. The most pronounced differences were found in the stimulus intensity parameters. CONCLUSIONS: CMAP scans made at hospital admission demonstrate several characteristics that can be used as an early indicator of GBS subtype.

Motor nerve excitability after childhood Guillain-Barré syndrome.

Residual motor nerve dysfunction after pediatric Guillain-Barré syndrome (GBS) was determined in an observational cross-sectional cohort study in patients who previously developed GBS during childhood (<18 years). Ulnar motor nerve dysfunction was defined by compound motor action potential (CMAP) scan in patients after a follow up of at least 1 year compared with age-matched healthy controls, in relation to clinical course and outcome. A total of 37 persons previously diagnosed with GBS in childhood were included with a mean age at current examination of 20.6 years (4-39 years). The median time between diagnosis and follow-up was 11 years (range: 1-22 years). CMAP scanning indicated ulnar motor nerve dysfunction in 25 (68%) participants. The most frequent abnormality was a reduction in nerve excitability observed both in those with residual limb weakness and in the majority of those with complete recovery. CMAP scan characteristics were not related to prognostic factors or outcome. In conclusion, GBS in childhood results in residual motor nerve excitability disturbances, even in those completely recovered, probably reflecting altered physiology of regenerated peripheral nerves.

Identifying fasciculation potentials in motor neuron disease: A matter of probability.

INTRODUCTION: Fasciculations, the spontaneous activity of single motor units (MUs) are characteristic, but nonspecific for motor neuron disease (MND). We aimed to identify MU discharge properties to optimally differentiate MND patients from healthy controls. METHODS: High-density surface electromyography recordings were performed in the thenar muscles during 10 min of rest. MU discharges were classified as "isolated" when the interspike intervals (ISIs) before and after were > 250 ms, "continual" when both ISIs were ≤ 250 ms, or as "other". RESULTS: In patients (n = 30) compared with controls (n = 14), more MUs were active (9 vs. 3, P < 0.001) and generated relatively more isolated discharges (35% vs. 10%, P = 0.01). Two or more MUs with isolated discharges occurred more frequently in patients compared with controls (24% vs. <1% of 10-s windows, P < 0.001). CONCLUSIONS: More frequent occurrence of multiple MUs showing isolated discharges may improve identification of patients with MND.

Electrically evoked multiplet discharges are associated with more marked clinical deterioration in motor neuron disease.

INTRODUCTION: The aim of this study was to determine whether electrically evoked multiplet discharges (MDs) are related to severity of clinical deterioration in motor neuron disease (MND). METHODS: Stimulated high-density surface electromyographic (HDsEMG) recordings were performed in thenar muscles. Data were collected from 31 MND patients. MDs from the HDsEMG recordings were determined at baseline. ALSFRS-R scores were obtained at baseline and at a maximum of 16 weeks follow-up. RESULTS: The presence of MDs was associated with progressive deterioration of ALSFRS-R score (P = 0.02) and fine motor function (FMF) (P < 0.001). Patients who had a higher number of motor units that generated MDs (r = 0.61, P < 0.001) and patients who had a higher number of MDs (as percentage of applied stimuli) (r = 0.59, P = 0.001) had a more severe decline in FMF. CONCLUSIONS: Electrically evoked MDs are associated with more marked clinical deterioration in patients with MND.

Increased supernormality in patients with multiplet discharges: Evidence for a common pathophysiological mechanism behind multiplets and fasciculations.

OBJECTIVE: To determine whether there is a relation between electrically evoked multiplet discharges (MDs) and motor axonal excitability properties. We hypothesized that electrically evoked MDs share their underlying pathophysiological mechanism with fasciculations. METHODS: High-density surface EMG and motor nerve excitability recordings of the thenar muscles were performed in 22 patients with motor neuron disease (MND) in their differential diagnosis and who were referred for EMG examination. RESULTS: Supernormality (hyperexcitable phase following the refractory period) was significantly increased in patients with MDs (n=10) compared to patients without MDs (n=12) (25.5% vs 17.0%; p=0.02). Depolarizing threshold electrotonus differed significantly between both groups as well (TEdpeak, 76.6% vs 66.6%, p<0.01; TEd90-100ms, 51.7% vs 44.3%, p<0.01) CONCLUSIONS: Our findings imply that the same pathophysiological excitability changes are involved in generating MDs and fasciculations. Yet, MDs may be quantified more easily, and may be more specific for abnormal distal excitability than fasciculations, because fasciculations may originate along the motor axon as well as in the neuron cell body. SIGNIFICANCE: MDs are potentially useful as objective measure of increased distal axonal excitability at individual motor unit level and might complement clinical studies in MND.

Diagnostic accuracy of electrically elicited multiplet discharges in patients with motor neuron disease.

OBJECTIVE: To determine and compare the diagnostic accuracy of electrically elicited multiplet discharges (MDs) and fasciculation potentials (FPs) in motor neuron disease (MND). METHODS: Patients were eligible when they had MND in their differential diagnosis and were referred for electromyogram (EMG). Stimulated high-density surface EMG of the thenar muscles was performed on the same day as standard EMG examination. High-density recordings were analysed for presence of MDs and needle EMG of any muscle investigated in the cervical region for presence of FPs. RESULTS: Of the 61 patients enrolled in this diagnostic study, 24 patients were clinically diagnosed with amyotrophic lateral sclerosis (ALS) and 11 patients with progressive muscular atrophy (PMA). Another diagnosis was made in 26 patients. Sixteen patients in whom MDs were detected were diagnosed with either ALS (n = 11) or PMA (n = 5; sensitivity = 47.1%, PPV = 94.1%). MDs were detected in only one patient initially diagnosed with PMA, but in whom later on, multifocal motor neuropathy could not be excluded (specificity = 96.2%). Electrically elicited MDs had a higher specificity than FPs (96.2% vs 53.9%, p < 0.001, n = 26) and lower sensitivity (47.1% vs 85.3%, p = 0.002, n = 34). When considering presence of MDs in MND as neurogenic EMG abnormality, lower motor neuron involvement of ≥ 1 EMG region increased from 50% to 73.5% (p = 0.008, n = 34). CONCLUSIONS: Electrically evoked MDs are highly specific for ALS and PMA and are an early sign of lower motor neuron dysfunction.

Safety status system for operating room devices.

BACKGROUND: Since the increase of the number of technological aids in the operating room (OR), equipment-related incidents have come to be a common kind of adverse events. This underlines the importance of adequate equipment management to improve the safety in the OR. OBJECTIVE: A system was developed to monitor the safety status (periodic maintenance and registered malfunctions) of OR devices and to facilitate the notification of malfunctions. The objective was to assess whether the system is suitable for use in an busy OR setting and to analyse its effect on the notification of malfunctions. METHODS: The system checks automatically the safety status of OR devices through constant communication with the technical facility management system, informs the OR staff real-time and facilitates notification of malfunctions. The system was tested for a pilot period of six months in four ORs of a Dutch teaching hospital and 17 users were interviewed on the usability of the system. RESULTS: The users provided positive feedback on the usability. For 86.6% of total time, the localisation of OR devices was accurate. 62 malfunctions of OR devices were reported, an increase of 12 notifications compared to the previous year. CONCLUSIONS: The safety status system was suitable for an OR complex, both from a usability and technical point of view, and an increase of reported malfunctions was observed. The system eases monitoring the safety status of equipment and is a promising tool to improve the safety related to OR devices.

Residual fatigue in Guillain-Barre 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.

Assessment of transverse ultrasonographic parameters to optimize carpal tunnel syndrome diagnosis in a case-control study.

INTRODUCTION: Transverse ultrasound measurements of the median nerve (MN) for diagnosis of carpal tunnel syndrome (CTS) suffer from inconsistent findings within and between patients and healthy subjects. The objective of this study was to improve ultrasound assessment of CTS. METHODS: In a case-control study (51 patients, 25 controls) we evaluated the performance gained by: (1) correcting for ultrasound probe angulation; (2) including active parameters such as forceful gripping of the hand; and (3) including hand flexor tendon parameters. RESULTS: Correcting ultrasound probe angulation increased the correct classification rate by 4.5%; including forceful gripping resulted in increasing it by 2.8%; and including the hand flexor tendon resulted in an increase of 1.3%. CONCLUSIONS: The best predictive model combines correcting probe angulation with forceful gripping parameters and hand flexor tendon parameters. However, the clinically most practical model might use only probe angulation correction.

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.

A new and fast approach towards sEMG decomposition.

The decomposition of high-density surface EMG (HD-sEMG) interference patterns into the contribution of motor units is still a challenging task. We introduce a new, fast solution to this problem. The method uses a data-driven approach for selecting a set of electrodes to enable discrimination of present motor unit action potentials (MUAPs). Then, using shapes detected on these channels, the hierarchical clustering algorithm as reported by Quian Quiroga et al. (Neural Comput 16:1661-1687, 2004) is extended for multichannel data in order to obtain the motor unit action potential (MUAP) signatures. After this first step, more motor unit firings are obtained using the extracted signatures by a novel demixing technique. In this demixing stage, we propose a time-efficient solution for the general convolutive system that models the motor unit firings on the HD-sEMG grid. We constrain this system by using the extracted signatures as prior knowledge and reconstruct the firing patterns in a computationally efficient way. The algorithm performance is successfully verified on simulated data containing up to 20 different MUAP signatures. Moreover, we tested the method on real low contraction recordings from the lateral vastus leg muscle by comparing the algorithm's output to the results obtained by manual analysis of the data from two independent trained operators. The proposed method showed to perform about equally successful as the operators.

Natural conduits for bridging a 15-mm nerve defect: comparison of the vein supported by muscle and bone marrow stromal cells with a nerve autograft.

OBJECT: The gold standard for reconstructing large nerve defects, the nerve autograft, results in donor-site morbidity. This detrimental consequence drives the search for alternatives. We used a vein filled with a small piece of fresh muscle to prevent the vein from collapsing and with bone marrow stromal cells (BMSCs) to enhance regeneration. METHODS: In 60 rats, a 15-mm sciatic nerve defect was bridged with a nerve autograft, a vein filled with muscle or a vein filled with muscle and BMSCs. Toe spread and pinprick were used to evaluate motor and sensory function. Compound muscle action potentials (CMAPs) and the gastrocnemius muscle index (GMI) were recorded to assess conduction properties and denervation atrophy. Extensive histology was performed to confirm presence of BMSCs and to evaluate regeneration by staining neural tissue for Schwann cells and neural growth factor. RESULTS: After 12 weeks, all animals responded with toe spread and pinprick reaction; significant differences were found between groups. Six weeks post grafting no difference was found comparing the GMI between the groups. Group I had a significant increase in GMI at 12 weeks compared to group II and group III. The CMAP measurements showed comparable results at 6 weeks post grafting. Twelve weeks after reconstruction, group I had significantly better results compared to group II and group III. Group III showed a tendency to outperform group II at 12 weeks postoperatively. Immunofluorescence analysis showed an increased number of Schwann cells in group III compared to group II. The BMSCs were visible 6 and 12 weeks postoperatively. CONCLUSIONS: This study is a step forward in the search for an alternative to the nerve autograft because it demonstrates the beneficial effect of BMSCs to a conduit. However, our data do not demonstrate sufficient benefit to warrant clinical implementation at this stage.

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

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.

Multiplet discharges after electrical stimulation: new evidence for distal excitability changes in motor neuron disease.

We hypothesized that action potentials evoked by distal stimulation might trigger ectopic activity (multiplet discharges, MDs). By studying MDs, we investigated the involvement of the axonal part of the peripheral motor neuron in amyotrophic lateral sclerosis (ALS) and progressive muscular atrophy (PMA). We performed stimulated high-density surface EMG recordings of the thenar muscles in 10 ALS/PMA patients, five recordings per patient over a three-month period. Furthermore, motor unit number estimates (MUNE) and ALSFRS-R scores were obtained in sessions 1 and 5. MDs were found in all patients, in 21% of the sampled motor units, and in response to 2.4% of the stimulations. The interspike interval range of the MD components was 2.9-6.5 ms, which is compatible only with a distal MD origin. The number of MDs, as percentage of the number of applied stimuli, was correlated with a decline in ALSFRS-R (r =0.80, p =0.006) and MUNE (r =0.72, p =0.02). In conclusion, MDs can be elicited with electrical stimulation in ALS and PMA patients. Analysis of MD characteristics provides further indications for pathophysiological excitability changes in the most distal part of the motor neuron. MDs are associated with clinical deterioration.

Ultrasonographic assessment of longitudinal median nerve and hand flexor tendon dynamics in carpal tunnel syndrome.

INTRODUCTION: Changes in subsynovial connective tissue (SSCT) in carpal tunnel syndrome (CTS) patients may result in altered dynamics; consequently, quantification of these dynamics might support objective diagnosis of CTS. METHODS: We measured and compared longitudinal excursion of the flexor digitorum superficialis and profundus tendons, the median nerve, and the SSCT between the most and least affected hands of 51 CTS patients during extension-to-fist motion. RESULTS: Median nerve and flexor digitorum superficialis tendon excursions in the most affected hands were smaller than in the least affected hands of the same patients, whereas the excursions of the flexor digitorum profundus were larger. Based on these excursions, logistic regression models classified between 67% and 86% of the hands correctly as having CTS. CONCLUSIONS: The altered hand dynamics in CTS patients may have implications for the pathophysiology and clinical evaluation of CTS, and ultrasound-based classification models may further support the diagnosis of CTS.

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.

Reproducibility of the CMAP scan.

INTRODUCTION: The 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. METHODS: Two 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. RESULTS: All 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. CONCLUSION: CMAP 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.