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.

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.

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.

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.

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.

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.

Histological validation of ultrasound-guided neurography in early nerve regeneration.

Ultrasound-guided near-nerve neurography is a new tool that can be used to assess nerve regeneration before reinnervation occurs. In this study, ultrasound-guided near-nerve measurements were validated against axon diameter counts in rabbits during a 15-week regeneration period after a crush lesion of their peroneal nerve. The course of the nerve was determined ultrasonically, and the active near-nerve needle electrode was maneuvered just next to the nerve under ultrasound guidance. Measured action potentials were compared with axon diameter counts from histological sections of these same nerves. A moderate to good positive correlation was found, which reached a maximum of 0.7 at a cut-off of 3 microm, corresponding to the minimal size of the myelinated axons. Our results suggest that, following a similar validation study in humans, ultrasound-guided near-nerve neurography may be clinically useful when early evaluation of nerve activity is needed.

Ultrasound-guided near-nerve neurography for early evaluation of nerve regeneration.

For early assessment of axonal outgrowth after trauma, the nerve is surgically exposed to enable compound nerve action potential (CNAP) recordings across the lesion site. Near-nerve neurography, with needle electrodes placed transcutaneously near the nerve, could be a minimally invasive alternative if the needle placement procedure and low reproducibility are improved. We developed ultrasound-guided near-nerve neurography, which facilitates needle placement, and assessed its potential for evaluating nerve regeneration. Measurements were performed at varying times after crush lesion of the peroneal nerve of 25 rabbits. To test if ultrasound-guided near-nerve signals could be measured prior to muscle reinnervation, they were compared with recordings of compound muscle action potentials. A comparison with conventional intra-operative CNAP recordings was made by measuring nerve signal amplitude with both techniques and by assessing reproducibility. In all cases where intra-operative signals could be measured, near-nerve signals were also detected. Compound nerve activity could be recorded after 5 weeks, whereas compound muscle activity appeared after approximately 8 weeks. Reproducibility was slightly better for near-nerve than for intra-operative recordings. We conclude that ultrasound-guided near-nerve neurography is able to assess nerve regeneration well before compound muscle activity can be detected. Its accuracy and reproducibility are similar to those of conventional intra-operative recordings.

Motor unit number estimation using high-density surface electromyography.

OBJECTIVE: To present a motor unit number estimation (MUNE) technique that resolves alternation by means of high-density surface EMG. METHODS: High-density surface EMG, using 120 EMG channels simultaneously, is combined with elements of the increment counting technique (ICT) and the multiple-point stimulation technique. Alternation is a major drawback in the ICT. The spatial and temporal information provided by high-density surface EMG support identification and elimination of the effects of alternation. We determined the MUNE and its reproducibility in 14 healthy subjects, using a grid of 8 x 15 small electrodes on the thenar muscles. RESULTS: Mean MUNE was 271+/-103 (retest: 290+/-109), with a coefficient of variation of 22% and an intra-class correlation of 0.88. On average, 22 motor unit potentials (MUPs) were collected per subject. The representativity of this MUP sample was quantitatively assessed using the spatiotemporal information provided by high-density recordings. CONCLUSIONS: MUNE values are relatively high, because we were able to detect many small MUPs. Reproducibility was similar to that of other MUNE techniques. SIGNIFICANCE: Our technique allows collection of a large MUP sample non-invasively by resolving alternation to a large extent and provides insight into the representativity of this sample. The large sample size is expected to increase MUNE accuracy.

Limb temperature and nerve conduction velocity during warming with hot water blankets.

Electrodiagnostic assessments of the peripheral nervous system often require limb warming. The traditional warming method, the hot water bath, has several disadvantages. We present an alternative: hot water blankets containing circulating water of a constant temperature. In addition to having practical advantages, these blankets allow for accurate and continuous monitoring of limb temperature and nerve conduction velocity (NCV) during warming. We therefore aimed to determine (1) the temperature dependence of the NCV of the median motor and sensory nerve, deep peroneal nerve, and sural nerve during warming with blankets, and (2) the optimal warming strategy for clinical purposes. We warmed the limbs of 10 subjects for 90 minutes with blankets set at a temperature of 41 degrees C. During warming, the NCV of the three nerves and distal motor latency of the two motor nerves were measured every 2(1/2) minutes. After 25 minutes of warming from an initial temperature of 28 degrees C, the NCV and distal motor latency of all nerves were within the normal range. However, after median nerve warming until a predefined temperature of 34 degrees C (i.e., for 17 minutes on average), two of nine subjects showed abnormal NCVs. We therefore conclude that for limb warming with hot water blankets, a fixed 25-minute warming period is optimal.

Significant reduction in neural adhesions after administration of the regenerating agent OTR4120, a synthetic glycosaminoglycan mimetic, after peripheral nerve injury in rats.

OBJECT: Extradural and intraneural scar formation after peripheral nerve injury frequently causes tethering and compression of the nerve as well as inhibition of axonal regeneration. Regenerating agents (RGTAs) mimic stabilizing and protective properties of sulphated glycosaminoglycan toward heparin-binding growth factors. The aim of this study was to assess the effect of an RGTA known as OTR4120 on extraneural fibrosis and axonal regeneration after crush injury in a rat sciatic nerve model. METHODS: Thirty-two female Wistar rats underwent a standardized crush injury of the sciatic nerve. The animals were randomly allocated to RGTA treatment or sham treatment in a blinded design. To score neural adhesions, the force required to break the adhesions between the nerve and its surrounding tissue was measured 6 weeks after nerve crush injury. To assess axonal regeneration, magnetoneurographic measurements were performed after 5 weeks. Static footprint analysis was performed preoperatively and at Days 1, 7, 14, 17, 21, 24, 28, 35, and 42 postoperatively. RESULTS: The magnetoneurographic data show no significant difference in conduction capacity between the RGTA and the control group. In addition, results of the static footprint analysis demonstrate no improved or accelerated recovery pattern. However, the mean pullout force of the RGTA group (67 +/- 9 g [mean +/- standard error of the mean]) was significantly (p < 0.001) lower than that of the control group (207 +/- 14 g [mean +/- standard error of the mean]). CONCLUSIONS: The RGTAs strongly reduce nerve adherence to surrounding tissue after nerve crush injury.

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 muscle's 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.

Continuous noninvasive monitoring of barbiturate coma in critically ill children using the Bispectral index monitor.

INTRODUCTION: Traumatic brain injury and generalized convulsive status epilepticus (GCSE) are conditions that require aggressive management. Barbiturates are used to lower intracranial pressure or to stop epileptiform activity, with the aim being to improve neurological outcome. Dosing of barbiturates is usually guided by the extent of induced burst-suppression pattern on the electroencephalogram (EEG). Dosing beyond the point of burst suppression may increase the risk for complications without offering further therapeutic benefit. For this reason, careful monitoring of EEG parameters is mandatory. A prospective study was conducted to evaluate the usefulness of the bispectral index suppression ratio for monitoring barbiturate coma. METHODS: A prospective observational pilot study was performed at a paediatric (surgical) intensive care unit, including all children with barbiturate-induced coma after traumatic brain injury or GCSE. The BIS (Bispectral index) monitor expresses a suppression ratio, which represents the percentage of epochs per minute in which the EEG was suppressed. Suppression ratios from the BIS monitor were compared with suppression ratios of full-channel EEG as assessed by quantitative visual analysis. RESULTS: Five patients with GCSE and three patients after traumatic brain injury (median age 11.6 years, range 4 months to 15 years) were included. In four patients the correlation between the suppression ratios of the BIS and EEG could be determined; the average correlation was 0.68. In two patients, suppression ratios were either high or low, with no intermediate values. This precluded determination of correlation values, as did the isoelectric EEG in a further two patients. In the latter patients, the mean +/- standard error BIS suppression ratio was 95 +/- 1.6. CONCLUSION: Correlations between suppression ratios of the BIS and EEG were found to be only moderate. In particular, asymmetrical EEGs and EEGs with short bursts (less than 1 second) may result in aberrant BIS suppression ratios. The BIS monitor potentially aids monitoring of barbiturate-induced coma because it provides continuous data on EEG suppression between full EEG registrations, but it should be used with caution.

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.

Quantitative EEG monitoring during cerebral air embolism and hyperbaric oxygen treatment in a pig model.

The purpose of this study was to evaluate the contribution of quantitative EEG (qEEG) to an animal model of cerebral air embolism (CAE). In 12 anesthetized pigs, air was injected into the internal carotid artery, and hyperbaric oxygen (HBO) treatment was started either after 3 minutes or after 60 minutes (United States Navy Treatment Table 6). Off-line spectral analysis was used to determine the frequency content of the EEG signal, and factor analysis was performed to determine the frequency ranges that optimally showed the changes in the power spectrum. Factor analysis revealed two factors that represented different and independent spectral changes during embolization: 0.5 to 7.3 Hz (band 1) and 26.4 to 30.3 Hz (band 2). Shortly after embolization, the power in both bands decreased to a minimum, representing an isoelectric EEG in 11 out of the 12 animals. EEG differences between animals were considerable, despite standardized doses of injected air, and qEEG can objectively assess and quantify these differences in immediate impact of air embolism on brain function. Also, qEEG enabled monitoring of the recovery from the initial embolic event and of the response on treatment. The initial recovery was much more protracted in band 2 than in band 1, but even after completing HBO treatment, qEEG values did not return to baseline values in all animals. In addition, two animals did not survive until the end of the HBO treatment, and qEEG proved to be superior to the other measured hemodynamic variables to detect and ensure a deterioration of brain function. This study showed that qEEG monitoring has significant additional value to monitoring HBO treatment.