Compound Motor Action Potential Amplitude Research Articles

Prevention of axonal loss after immediate dosage titration of immunoglobulin in multifocal motor neuropathy.

To evaluate whether ongoing axonal loss can be prevented in multifocal motor neuropathy (MMN) treated with immunoglobulin G (IgG), a group of patients with a median disease duration of 15.7 years (range: 8.3-37.8), treated with titrated dosages of immunoglobulins, was studied electrophysiologically at time of diagnosis and at follow-up. At follow-up, the Z-score of the compound motor action potential amplitude of the median, fibular, and tibial nerves and the neurological performances were determined. In seven patients with a treatment-free period of 0.3 years (0.2-0.4), there was no progression of axonal loss (p = 0.2), whereas a trend toward further axonal loss by 1.3 Z-scores (0.9-17.0, p = 0.06) was observed in five patients with a treatment-free period of 4.0 years (0.9-9.0). The axonal loss in the group with a short treatment delay was significantly smaller than in the group with a longer treatment delay (p = 0.02). Also, there was an association between treatment delay and ongoing axonal loss (p = 0.004). The electrophysiological findings at follow-up were associated with the isokinetic strength performance, the neurological impairment score, and the disability, supporting the clinical relevance of the electrophysiological estimate of axonal loss. Swift initiation of an immediately titrated IgG dosage can prevent further axonal loss and disability in continuously treated MMN patients.

Volume loss during muscle reinnervation surgery is correlated with reduced CMAP amplitude but not reduced force output in a rat hindlimb model.

Introduction: Muscle reinnervation (MR) surgery offers rehabilitative benefits to amputees by taking severely damaged nerves and providing them with new denervated muscle targets (DMTs). However, the influence of physical changes to muscle tissue during MR surgery on long-term functional outcomes remains understudied. Methods: Our rat hindlimb model of MR surgery utilizes vascularized, directly neurotized DMTs made from the lateral gastrocnemius (LG), which we employed to assess the impact of muscle tissue size on reinnervation outcomes, specifically pairing the DMT with the transected peroneal nerve. We conducted MR surgery with both DMTs at full volume and DMTs with partial volume loss of 500mg at the time of surgery (n = 6 per group) and measured functional outcomes after 100days of reinnervation. Compound motor action potentials (CMAPs) and isometric tetanic force production was recorded from reinnervated DMTs and compared to contralateral naïve LG muscles as positive controls. Results: Reinnervated DMTs consistently exhibited lower mass than positive controls, while DMTs with partial volume loss showed no significant mass reduction compared to full volume DMTs (p = 0.872). CMAP amplitudes were lower on average in reinnervated DMTs, but a broad linear correlation also exists between muscle mass and maximum CMAP amplitude irrespective of surgical group (R2 = 0.495). Surprisingly, neither MR group, with or without volume loss, demonstrated decreased force compared to positive controls. The average force output of reinnervated DMTs, as a fraction of the contralateral LG's force output, approached 100% for both MR groups, a notable deviation from the 9.6% (±6.3%) force output observed in our negative control group at 7days post-surgery. Tissue histology analysis revealed few significant differences except for a marked decrease in average muscle fiber area of reinnervated DMTs with volume loss compared to positive controls (p = 0.001). Discussion: The results from our rat model of MR suggests that tissue electrophysiology (CMAPs) and kinesiology (force production) may recover on different time scales, with volumetric muscle loss at the time of MR surgery not significantly reducing functional outcome measurements for the DMTs after 100days of reinnervation.

Nusinersen induces detectable changes in compound motor action potential response in spinal muscular atrophy type 1 patients with severe impairment of motor function

BackgroundMost long-term affected spinal muscular atrophy (SMA) type 1 patients have severe impairment of motor function and are dependent on mechanical ventilation with tracheostomy. The efficacy and safety of nusinersen in these patients have not been established. MethodsWe retrospectively evaluated the efficacy of intrathecal nusinersen treatment in patients with SMA type 1 who continued treatment for at least 12 months. There were three patients enrolled in our study (3, 4 and 16 years of age) who had severe impairment of gross motor function without head control or the ability to roll over. All three needed mechanical ventilation with tracheostomy and tube feeding. Motor function was assessed using the Children s Hospital of Philadelphia infant test of neuromuscular disorders (CHOP-INTEND) and the caregivers’ evaluations. Concurrently, we examined nerve conduction longitudinally and compared compound motor action potential (CMAP) amplitudes. ResultsAll patients continued nusinersen administration without significant adverse events for more than three years. While CHOP-INTEND scores did not remarkably increase, according to the caregivers, all three patients had improved finger or facial muscle movements that enabled them to make their intentions understood. Some CMAPs before treatment were not identified but became traces after nusinersen administration. ConclusionsThe improvement in motor function that leads to smoother communication could be a basis for continuing nusinersen treatment. Currently available motor function scorings are not efficient for assessing therapeutic interventions in SMA patients with medical care complexity. Longitudinal nerve conduction studies could be an objective indicator.

Novel automated “score mapping” of diaphragmatic compound motor action potential for the early detection of phrenic nerve injury during cryoablation

The proximity of phrenic nerve to right sided pulmonary veins (PV) make it susceptible to injury during cryoballoon ablation (CBA) for atrial fibrillation (AF). Monitoring of diaphragmatic compound motor action potentials (CMAP) obtained from lead aVF or modified surface ECG leads placed along the diaphragm have been used for early detection of phrenic nerve injury (PNI). 1 Schaerli N. Badertscher P. Spies F. et al. A Simplified Method to Detect Phrenic Nerve Injury During Cryoballoon Ablation of Atrial Fibrillation Using Lead aVF of the Surface ECG. Circ Arrhythm Electrophysiol. 2021 Aug; 14e009986https://doi.org/10.1161/CIRCEP.121.009986 Crossref Scopus (0) Google Scholar Thirty percent drop in CMAP amplitude has been shown in studies as the threshold for prevention of PNI. 2 Miyazaki S. Hachiya H. Taniguchi H. et al. Prospective Evaluation of Bilateral Diaphragmatic Electromyograms During Cryoballoon Ablation of Atrial Fibrillation. JCE. 2015; 26: 622-628 Google Scholar However, CMAP signals may be susceptible to respiratory variations, catheter movement, inadequate baseline amplitude making it difficult to monitor the change in CMAP. 3 Sharma P.S. Padala S.K. Thompson J.J. Gunda S. Koneru J.N. Ellenbogen K.A. Factors Influencing Diaphragmatic Compound Motor Action Potentials During Cryoballoon Ablation for Atrial Fibrillation. JCE. 2016; 7: 1384-1389 Google Scholar Score-map of the CMAP using template matching with 3D electroanatomic mapping system can be used to automate the monitoring of CMAP. The aims of this study were to assess the relationship of change in CMAP amplitude with change in score-map and then use the automated score-map prospectively for early detection of PNI during CBA.

When does phrenic nerve injury recover after cryoballoon ablation? Data from Japanese multicenter registry

Abstract Funding Acknowledgements Type of funding sources: None. Background Although phrenic nerve injury (PNI) is most frequently encountered complication in cryoballoon ablation, it recovered in most cases. However, the duration of persisting PNI has not been fully investigated yet. Purpose This study sought to confirm the clinical course of PNI after the procedure in cases in which reduction of diaphragmatic compound motor action potential (CMAP)was confirmed during cryoballoon ablation of right-sided pulmonary veins (PVs). Methods We retrospectively analyzed a total of 237 patients who experienced right PNI confirmed by the CMAP amplitude reduction during cryoballoon ablation in 4 Japanese centers. Cryoballooon ablation of right-sided PVs were performed under CMAP monitoring in all cases, and once CMAP amplitude reduction was observed, freezing was immediately interrupted with a double stop technique. The recovery of PNI was confirmed by chest X-ray, and transient PNI was defined as one recovering before the discharge. Results Among 237 patients, PNI occurred during cryoballoon ablation of right superior PV and right inferior PV in 166 and 71 patients, respectively. The mean freezing time to PNI was 126.9±45.6 seconds and the mean balloon temperature when PNI occurred was -50.2±7.5°C. After PNI was confirmed, additional cryoballoon ablation of the same PV or the other ipsilateral PV was performed under CMAP monitoring in 29 and 97 patients, respectively. Transient PNI accounted for 53.2% of patients with PNI (126 out of 237 patients). Among the remaining 111 patients, the PNI recovery was confirmed within 3 months, 6 months or 12 months after the procedure in 42(37.8%), 55 (49.5%), 74 (66.7%) patients, respectively. When we excluded 32 patients who did not undergo sufficient follow-up of chest X-ray, only 5 patients (2.4%) still suffered from PNI at 12 months after the ablation, and the PNI recovery was confirmed after more than 12 months in 3 out of them. When we compared patients who suffered from PNI at 6 months after the procedure with those who did not, there was no significant difference in nadir balloon temperature (-50.4±6.9°C; for PNI recovery [-] vs -50.0±7.8°C; for PNI recovery [+], p=0.75). When freezing time was less than 60 seconds, PNI recovered within 6 months after ablation in all cases, although 23.2% of the patients in whom freezing time was 60 seconds or more still suffered from PNI at 6 months after the procedure (p=0.045). Conclusion The right-sided PNI confirmed by the CMAP amplitude reduction during cryoballoon ablation recovers within a couple of days in half of cases, and it rarely persists more than 12 months after the procedure. When freezing was interrupted less than 60 seconds, it is highly expected that PNI recovers within 6 months.

Utilizing novel recurrent laryngeal motor nerve conduction studies to characterize the aging larynx: A pilot study.

Age-related changes to the larynx are associated with dysphonia and contribute to reduced quality of life. This study utilizes recurrent laryngeal motor nerve conduction studies (rlMNCS) to determine if neurophysiologic changes occur in the aging larynx using an aging rat model. Animal study. In vivo rlMNCS were performed in 10 young hemi-larynges (3-4 months) and 10 aged hemi-larynges (18-19 months) rats (Fischer 344 × Brown Norway F344BN). Recording electrodes were placed into the thyroarytenoid (TA) muscle through direct laryngoscopy. Recurrent laryngeal nerves (RLNs) were directly stimulated with bipolar electrodes. Compound motor action potentials (CMAPs) were obtained. RLN cross-sections were stained with toluidine blue. Axon count, myelination, and g-ratio were quantified utilizing AxonDeepSeg analysis software. rlMNCS were successfully obtained in all animals. Mean CMAP amplitude and negative durations in young rats were 3.58 ± 2.20 mV and 0.93 ± 0.14 mS (mean dif: 0.17; 95% CI: -2.21 to 2.54), respectively, and 3.74 ± 2.81 mV and 0.98 ± 0.11 mS (mean dif: 0.050; 95% CI: -0.07 to 0.17). No significant differences in onset latency or negative area were observed. Mean axon count in young rats (176 ± 35) was comparable to that in old rats (173 ± 31). Myelin thickness and g-ratio did not differ between groups. There were no statistically significant differences in RLN conduction or axon histology between young and aged rats in this pilot study. This work provides a basis for future, adequately powered studies, and may lead to a tractable animal model to study the aging larynx. 5.

Longitudinal Assessment of Timed Function Tests in Ambulatory Individuals with SMA Treated with Nusinersen.

Ambulatory individuals with spinal muscular atrophy experience weakness and impairments of speed and endurance. This leads to decreased motor skill performance required for daily living including transitioning from floor to stand, climbing stairs, and traversing short and community distances. Motor function improvements have been reported in individuals receiving nusinersen, but changes in timed functional tests (TFTs) which assess shorter distance walking and transitions have not been well documented. To evaluate changes in TFT performance over the course of nusinersen treatment in ambulatory individuals with SMA and identify potential factors [age, SMN2 copy number, BMI, Hammersmith Functional Motor Scale Expanded (HFMSE score), Peroneal Compound Motor Action Potential (CMAP) amplitude] associated with TFT performance. Nineteen ambulatory participants receiving nusinersen were followed from 2017 through 2019 (range: 0-900 days, mean 624.7 days, median 780 days); thirteen of 19 (mean age = 11.5 years) completed TFTs. The 10-meter walk/run test, time-to-rise from supine, time-to-rise from sitting, 4-stair climb, 6-minute walk test (6MWT), Hammersmith Expanded and peroneal CMAP were assessed at each visit. Linear mixed-effects models were used to evaluate unadjusted and adjusted changes in these outcomes over time. Apart from time to rise from sitting and from supine, all TFTs were found to improve over the course of treatment after adjusting for baseline age and BMI. Improvement in TFTs over time in patients with SMA treated with nusinersen suggests that shorter TFTs may have value to assess individuals with SMA who have or later gain ambulatory function during treatment.

AB-453068-1 NOVEL ‘SCORE-MAPPING’ OF DIAPHRAGMATIC COMPOUND MOTOR ACTION POTENTIAL FOR EARLY DETECTION OF PHRENIC NERVE INJURY DURING CRYOABLATION

The proximity of the phrenic nerve to right-sided pulmonary veins makes it susceptible to injury during cryoballoon ablation (CBA) for atrial fibrillation (AF). Although there are no specific preprocedural predictors for phrenic nerve injury (PNI), monitoring of diaphragmatic compound motor action potentials (CMAP) has been used for the early detection of PNI. A 30% drop in CMAP amplitude has been shown in animal and clinical studies as the threshold for the prevention of PNI The aims of this study were to assess the relationship of change in CMAP amplitude with change in score map and then use the automated score map prospectively for early detection of PNI during CBA In the first half of the study, we paced the phrenic nerve at 10,8,6,4,2 milliamperes or till loss of capture in 20 pts. The relationship between the change in amplitude of CMAP with a corresponding change in the score map was studied by linear regression. 30% drop in CMAP amplitude was associated with a score map of 89%(R2 0.77). In the second half of the study, we used a score map threshold of 90% and studied 84 pts. Ablation was stopped if the score map of CMAP dipped below 90% consistently for >4 beats to take respiratory variation into account A total of 174 cryo applications were done for the right-sided veins in 84 pts. A consistent score-map >98% was obtained in all pts before the beginning of the CBA. Ablation had to be stopped in 13 pts due to a drop in the score map or CMAP amplitude or decreased diaphragm contraction. 5 pts had transient PNI. Change in score map was noticeable before change in CMAP amplitude or decrease in diaphragm contraction. In 8 pts drop in the score map was attributed to catheter movement which was noted by the change in catheter position on the 3D mapping system. Score-map of CMAP returned to >98% with catheter adjustment or within 5 minutes of ablation termination along with improvement of CMAP amplitude in all cases. No pts were noted to have persistent PNI at the end of the procedure Beat-to-beat changes in CMAP amplitude can be noted with respiratory variation or catheter movement making it difficult to monitor the change in amplitude. By using an automated score rather than continuously measuring CMAP amplitude, score mapping can make monitoring changes in CMAP amplitude easier. This descriptive study demonstrates that a 90 % score-map threshold correlates with a 30% drop in CMAP amplitude and can be safely and reliably used for the early detection of PNI

Multisequence magnetic resonance neurography of brachial and lumbosacral plexus in chronic inflammatory demyelinating polyneuropathy: correlations with electrophysiological parameters and clinical features

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare and challenging demyelinating disorder. It is necessary to increase our understanding of potential connections between imaging, electromyography, and clinical characteristics. The aim of this study was to evaluate the relationships between multisequence magnetic resonance neurography (MRN) findings, electrophysiological parameters, and clinical characteristics in CIDP patients. A cross-sectional study. Overall, 51 CIDP patients underwent MRN of the brachial and lumbosacral plexus, and nerve conduction studies. The inflammatory Rasch-built overall disability scale (I-RODS) questionnaire, CIDP disease activity status (CADS) scale, and muscle strength scores were evaluated by two neurologists. Electrophysiological parameters, clinical information, and multiparameter-MRN were analyzed for correlations. Multiparameter-MRN includes diameter, nerve-to-muscle T2 signal intensity ratio (nT2), contrast-enhanced ratio (CR), fractional anisotropy (FA), and apparent diffusion coefficient (ADC) of bilateral plexus nerve roots. Electrophysiological parameters that were not elicited were significantly higher in the lower extremities than in the upper extremities, and those were higher in sensory nerve conduction than in motor. There were moderate correlations between motor nerve conduction velocity and distal motor latency in nerve diameter, nT2, FA, and ADC, respectively (|r|, 0.45-0.64, p < 0.05). The correlations between CR and sensory nerve conduction velocity and peak latency were moderate, and ADC had a positive correlation with compound motor action potential amplitude (|r|, 0.45-0.63). FA correlated negatively with the course (r = -0.62) and cerebrospinal fluid (CSF) protein (r = -0.41), whereas ADC had correlated positively with CSF protein (r = 0.34). Only CR had a moderately negative correlation with CADS (r's = -0.57). Muscle strength in all extremities was positively correlated with FA (r's range, 0.41-0.49). There was no significant correlation between I-RODS scores and multiparameter-MR. MRN-derived multiparameter [nerve size, nT2, and diffusion tensor imaging (DTI) parameters] could serve as quantitative biomarkers of myelin sheath integrity in CIDP. DTI parameters and CR correlated with clinical characteristics better than morphological parameters-MR for CIDP patients.

Analysis of Electrodiagnostic Recovery after Carpal Tunnel Release: A Retrospective Study

Objective: We investigated the factors affecting electrodiagnostic (EDX) parameters after carpal tunnel release (CTR).Methods: Thirty-nine cases with clinically diagnosed carpal tunnel syndrome who received CTR and EDX studies before and after CTR were enrolled in this study. We analyzed EDX parameters such as distal onset latency and the amplitude of median compound motor action potentials (CMAPs) and sensory nerve action potentials (SNAPs).Results: Among 39 cases, 24 (61.5%) showed improvement of at least 1 grade, based on Bland’s scale, after CTR. Follow-up EDX studies were performed 6 to 36 months after CTR. Improvement on Bland’s scale was shown in 50% of patients who received follow-up EDX studies at 6 and 12 months after CTR and in all patients who received follow-up at 24 and 36 months. The EDX parameters showed significant recovery. Younger patients showed greater recovery of SNAP amplitude (p = 0.021, r = -0.369) after CTR. The preoperative severe group showed greater recovery of CMAP (both amplitude and latency) than the non-severe group (p = 0.011 and p = 0.038, respectively).Conclusion: We confirmed the effectiveness of CTR through EDX studies. Age and preoperative EDX severity can affect the recovery of EDX parameters after CTR.

Assessing the therapeutic impact of resveratrol in ALS SOD1-G93A mice with electrical impedance myography.

To aid in the identification of new treatments for amyotrophic lateral sclerosis (ALS), convenient biomarkers are needed to effectively and uniformly measure drug efficacy. To this end, we assessed the effects of the nutraceutical resveratrol (RSV) on disease onset and overall survival in SOD1-G93A (ALS) mice and compared several standard biomarkers including body mass, motor score (MS), paw grip endurance (PGE), and compound motor action potential (CMAP) amplitude, with the technique of electrical impedance myography (EIM) to follow disease progression. Eighteen ALS mice (nine females, nine males) received RSV in the chow (dose: 120 mg/kg/day) starting at 8 weeks of age; 19 ALS mice (nine females, 10 males) received normal chow; 10 wild type (WT) littermates (five females, five males) fed standard chow served as controls. Biomarker assessments were performed weekly beginning at 8 weeks. No differences in either disease onset or overall survival were found between RSV-treated and untreated ALS mice of either sex; moreover, all biomarkers failed to identify any beneficial effect of RSV when administered at this dose. Therefore, for the comparative evaluation of the ability of the various biomarkers to detect the earliest symptoms of disease, data from all animals (i.e., RSV-treated and untreated ALS mice of both sexes) were combined. Of the biomarkers tested, EIM impedance values, i.e., surface EIM longitudinal phase at 50 kHz (LP 50 kHz), and CMAP amplitude showed the earliest significant changes from baseline. LP 50 kHz values showed a rate of decline equivalent to that of CMAP amplitude and correlated with both PGE and CMAP amplitude [Spearman rho = 0.806 (p = 0.004) and 0.627 (p = 0.044), respectively]. Consistent with previous work, these findings indicate that surface EIM can serve as an effective non-invasive biomarker for preclinical drug testing in rodent models of ALS.

A new mouse model of Charcot-Marie-Tooth 2J neuropathy replicates human axonopathy and suggest alteration in axo-glia communication.

Myelin is essential for rapid nerve impulse propagation and axon protection. Accordingly, defects in myelination or myelin maintenance lead to secondary axonal damage and subsequent degeneration. Studies utilizing genetic (CNPase-, MAG-, and PLP-null mice) and naturally occurring neuropathy models suggest that myelinating glia also support axons independently from myelin. Myelin protein zero (MPZ or P0), which is expressed only by Schwann cells, is critical for myelin formation and maintenance in the peripheral nervous system. Many mutations in MPZ are associated with demyelinating neuropathies (Charcot-Marie-Tooth disease type 1B [CMT1B]). Surprisingly, the substitution of threonine by methionine at position 124 of P0 (P0T124M) causes axonal neuropathy (CMT2J) with little to no myelin damage. This disease provides an excellent paradigm to understand how myelinating glia support axons independently from myelin. To study this, we generated targeted knock-in MpzT124M mutant mice, a genetically authentic model of T124M-CMT2J neuropathy. Similar to patients, these mice develop axonopathy between 2 and 12 months of age, characterized by impaired motor performance, normal nerve conduction velocities but reduced compound motor action potential amplitudes, and axonal damage with only minor compact myelin modifications. Mechanistically, we detected metabolic changes that could lead to axonal degeneration, and prominent alterations in non-compact myelin domains such as paranodes, Schmidt-Lanterman incisures, and gap junctions, implicated in Schwann cell-axon communication and axonal metabolic support. Finally, we document perturbed mitochondrial size and distribution along MpzT124M axons suggesting altered axonal transport. Our data suggest that Schwann cells in P0T124M mutant mice cannot provide axons with sufficient trophic support, leading to reduced ATP biosynthesis and axonopathy. In conclusion, the MpzT124M mouse model faithfully reproduces the human neuropathy and represents a unique tool for identifying the molecular basis for glial support of axons.

Neurophysiological Hallmarks of Axonal Degeneration in CIDP Patients: A Pilot Analysis.

In this work, we aim to identify sensitive neurophysiological biomarkers of axonal degeneration in CIDP patients. A total of 16 CIDP patients, fulfilling the clinical and neurophysiological criteria for typical CIDP, treated with subcutaneous immunoglobulin (ScIg) (0.4 g/kg/week) were evaluated at baseline (before ScIg treatment) and after long-term treatment with ScIg (24 months) by clinical assessment scales, nerve conduction studies (NCS) and electromyography (EMG). Conventional and non-conventional neurophysiological parameters: motor unit potential (MUP) analysis, MUP thickness and size index (SI)] and interference pattern (IP) features were evaluated after long-term treatment (24 months) and compared with a population of 16 healthy controls (HC). An increase of distal motor latency (DML) and reduced compound motor action potential (CMAP) amplitude and area in CIDP patients suggest axonal damage of motor fibers, together with a significant increase of MUP amplitude, duration and area. Analysis of non-conventional MUP parameters shows no difference for MUP thickness; however, in CIDP patients, SI is increased and IP area and amplitude values are lower than HC. Despite clinical and neurophysiological improvement after ScIg treatment, neurophysiological analysis revealed axonal degeneration of motor fibers and motor unit remodeling. Correlation analysis shows that the axonal degeneration process is related to the diagnostic and therapeutic delay. MUP area and SI parameters can detect early signs of axonal degeneration, and their introduction in clinical practice may help to identify patients with the worst outcome.

Value of short exercise and short exercise with cooling tests in diagnosis of recessive form of myotonia congenita (Becker disease) - are sex differences important?

In myotonia congenita (MC), activation with exercise or cooling can induce transient changes in compound motor action potential (CMAP) parameters, thus providing a guide to genetic analysis. We performed the short exercise test (SET) and the short exercise test with cooling (SETC) in 30 patients with genetically confirmed Becker disease (BMC) to estimate their utility in the diagnosis of BMC. Although we observed a significant decrease in CMAP amplitude immediately after maximal voluntary effort in both tests in the whole BMC group, in men this decline was significantly smaller than in women, especially in SET. Clinical implications/future directions: In men with a clinical suspicion of BMC, a small decrease in CMAP amplitude in SET together with a typical decline in SETC does not exclude the diagnosis of BMC. Our results show a sex-specific difference in chloride channel function in BMC, which needs further investigation.

Clinical and Electrophysiological Changes in Pediatric Spinal Muscular Atrophy after 2 Years of Nusinersen Treatment.

In the new therapeutic era, disease-modifying treatment (nusinersen) has changed the natural evolution of spinal muscular atrophy (SMA), creating new phenotypes. The main purpose of the retrospective observational study was to explore changes in clinical evolution and electrophysiological data after 2 years of nusinersen treatment. We assessed distal compound motor action potential (CMAP) on the ulnar nerve and motor abilities in 34 SMA patients, aged between 1 and 16 years old, under nusinersen treatment, using specific motor scales for types 1, 2 and 3. The evaluations were performed at treatment initiation and 26 months later. There were registered increased values for CMAP amplitudes after 2 years of nusinersen, significantly correlated with motor function evolution in SMA type 1 patients (p < 0.005, r = 0.667). In total, 45% of non-sitters became sitters and 25% of sitters became walkers. For SMA types 1 and 2, the age at the treatment initialization is highly significant (p < 0.0001) and correlated with treatment yield. A strong negative correlation (r = −0.633) was observed for SMA type 1 and a very strong negative correlation (r = −0.813) for SMA type 2. In treated SMA cases, the distal amplitude of the CMAP and motor functional scales are important prognostic factors, and early diagnosis and treatment are essential for a better outcome.

Temporary reversal of nerve and muscle dysfunction by serial electrical stimulation in critical illness neuromyopathy

ObjectiveCritical Illness Neuromyopathy (CIPNM) is a complication in sepsis patients with still enigmatic disease mechanisms. We investigated a novel electrical stimulation method to better define neuromuscular dysfunction in patients with CIPNM. MethodsWe studied 18 sepsis CIPNM patients on intensive care units, 13 at an early and 5 at a later disease stage, 7 sepsis control, and 8 neuropathy control patients. We applied slow conditioning electrical pulses at motor nerves and directly at the muscle to investigate a facilitation phenomenon (FP) of small or absent compound motor action potentials (CMAPs). ResultsSerial pulses induced a 2 to 490-fold increase in CMAP amplitudes in 17/18 Intensive Care Unit (ICU)-CIPNM patients (p < 0.001). These effects were short lived and reproducible. Direct muscle stimulation in the tibialis anterior muscle resulted in up to 130-fold FP in 7/9 patients tested (p < 0.01). In 4/5 post-ICU CIPNM patients FP was up to 10-fold. None of the 7 ICU sepsis control patients without CIPNM with similar disease severity and none of 8 neuropathy patients showed FP (p < 0.001). On needle EMG only 5/16 ICU patients tested revealed spontaneous activity. ConclusionsConditioning electrical stimulation detected a functional component of the disease process showing temporary improvement in sepsis-associated CIPNM. SignificanceNew test differentiates functional from degenerative pathology.

Clinical features of Guillain-Barré syndrome with anti-neurofascin 155 antibody.

Anti-neurofascin 155 (NF155) antibody has been discovered in chronic demyelinating conditions. However, the positive rate and clinical description were insufficient in acute demyelinating conditions, such as Guillain-Barré syndrome (GBS). This study aimed to explore the positive rate of anti-NF155 antibody in GBS patients and determine whether there were unique clinical characteristics in these patients. Serum anti-NF155 antibody was detected from 94 GBS patients and 50 sex- and age-matched healthy controls using cell-based assay and tissue-based assay with immunostaining of mouse teased sciatic nerve fibers. Clinical characteristics, laboratory data, and electrophysiology examinations were retrospectively collected. Seven of 94 (7.45%) GBS patients were positive for anti-NF155 antibody, and the main IgG subclass was IgG1. Compared with anti-NF155 antibody-negative GBS patients, anti-NF155 antibody-positive GBS patients had a higher GBS disability score at nadirs (p=.010), higher modified Erasmus GBS outcome score (p=.022), higher rate of abnormal compound motor action potential (CMAP) amplitude (p=.002), higher frequency of prolonged F-wave latency (p < .001), lower frequency of abnormal sensory conduction velocity (p < .001) and sensory nerve action potential amplitude (p < .001), more axonal type (p=.040), and poorer therapeutic effect (p=.017). Anti-NF155 antibody exists in a small portion of GBS patients. Anti-NF155 antibody-positive GBS patients possibly have a more severe clinical course, less sensory nerves involved, higher proportion of axonal type, poorer therapeutic effect, and worse prognosis, but the pathogenicity of the anti-NF155 antibody in GBS needs further study.

Different electrophysiology patterns in GNE myopathy

BackgroundGNE myopathy is a rare distal myopathy caused by mutations of the GNE gene. A few cases of GNE myopathy accompanied by neurogenic features of electrophysiology mimicking hereditary motor neuropathy were reported recently. We confirmed this feature and described the clinical phenotype and mutations of GNE myopathy in these rare cases.ResultsThe absence of lower limb tendon reflexes, decreased compound muscle action potentials in lower leg motor nerves, and neurogenic pattern of electromyography suggested neuropathy in four patients. However, muscle pathology revealed a predominantly myogenic pattern. The follow-up electroneurography results implied that the compound motor action potential amplitudes deteriorated over time. Next-generation sequencing identified three novel variants of the GNE gene, c.2054T > C (p.Val685Ala), c.424G > A (p.Gly142Arg) and c.944T > C (p.Phe315Ser), as well as two hotspot mutations, c.115C > T(p.Arg39*) and c.620A > T(p.Asp207Val), in these patients. These novel mutations cosegregated with disease in the family.ConclusionsThese rare cases supported the existence of neurogenic features of electrophysiology different from the typical myopathic pattern of GNE myopathy.

P 72 Antibody depletion in nodo-paranodopathy: Clinical and electrophysiological long-term follow-up

Nodo-paranodopathies are rare immune-mediated neuropathies with autoantibodies against proteins of the node of Ranvier. The antibodies cause conduction failure and a destruction of nodal architecture in vivo and in vitro. Affected patients show severe motor and sensory involvement and signs of demyelination in electroneurography, fulfilling EFNS/PNS criteria for CIDP. Response to standard treatment is poor, but good clinical response to rituximab has been reported. Little is known about long-term outcome after antibody depletion and electroneurographic follow-up. We conducted a cohort study of 7 patients with neuropathy with anti-paranodal antibodies treated at the University Hospital of Würzburg (n = 3 anti-contactin-1, n = 4 anti-Caspr-1) who showed an antibody decrease in the course of the disease either spontaneously (n = 2) or treatment-induced by B-cell depletion with Rituximab (n = 5). Antibody titers and Neurofilament Light-Chain (NfL) levels were assessed at first diagnosis/ recruitment and in follow-up serum samples by ELISA and Ella. Clinical data, scores and electrophysiological data were assessed retrospectively with a mean follow-up period of 48.6 (8-78) months and compared using paired t-test and Spearman correlation. At recruitment, mean disease duration was 43.6 (0.25-180) months. Patients showed sensorimotor tetraparesis with a mean Overall Disability Sum Score (ODSS) of 7.43 (5-10) and MRC sum score of 48.29 (40-57). The antibody titer ranged from 1:100 – 1:10,000 and did not correlate with inter-individual disease severity. Electroneurography revealed demyelinating features with highly elevated distal motor latency (dml), loss/ reduction of F-waves and reduced nerve conduction velocity, but also signs of severe, length-dependent compound motor action potential (CMAP) amplitude decrease and spontaneous activity in electromyography in 5/ 7 patients. After antibody depletion, we found a significant reduction in the Overall Disability Sum Score (ODSS, p < 0.007) and improvement in the MRC sum score. Electrophysiological demyelinating parameters improved significantly. The mean increase in tibial nerve dml correlated with the increase in MRC sum score (r = 0.922, p < 0.003). Median nerve CMAP amplitudes increased significantly (p < 0.009), with a significant negative correlation to ODSS (r = -0.7, p < 0.03). Tibial nerve CMAP on the other hand remained severely reduced. In patients with autoantibody-mediated nodo-paranodopathy, the depletion of antibodies leads to a clinical and electrophysiological improvement, even after a long disease duration. In our cohort, distal, length dependent axonal damages could not be fully reversed. Our data therefore suggest that early antibody depletion should be a main therapeutic goal in nodo-paranodopathy. Although the antibody titer cannot be used as an inter-individual indicator of disease severity, it may serve as a valuable intra-individual marker for treatment reevaluation and prognosis.

Compound Motor Action Potentials During a Modest Nerve Crush.

Nerve crush injury results in axonotmesis, characterized by disruption of axons and their myelin sheaths with relative sparing of the nerve’s connective tissue. Despite the widespread use of crush injury models, no standardized method for producing these lesions has been established. We characterize a crush model in which a narrow forceps is used to induce a modest and controlled compressive injury. The instantaneous compound motor action potential (CMAP) is monitored in situ and in real-time, allowing the characterization of neuromuscular response during and after injury. The tibial nerves of 11 anesthetized rats were surgically isolated. After the placement of electrodes, CMAPs were elicited and registered using a modular-data-acquisition system. Dumont-#5 micro-forceps were instrumented with a force transducer allowing force measurement via a digital sensor. Baseline CMAPs were recorded prior to crush and continued for the duration of the experiment. Nerve crushing commenced by gradually increasing the force applied to the forceps. At a target decrease in CMAP amplitude of 70%–90%, crushing was halted. CMAPs were continually recorded for 5–20 min after the termination of the crushing event. Nerves were then fixed for histological assessment. The following post-crush mean values from 19 trials were reported: peak CMAP amplitude decreased by 81.6% from baseline, duration of crush was 17 sec, rate of applied force was 0.03 N/sec, and maximal applied force was 0.5 N. A variety of agonal phenomena were evident post-lesion. Following the initial decrease in CMAP, 8 of 19 trials demonstrated a partial and transient recovery, followed by a further decline. Thirteen trials exhibited a CMAP amplitude near zero at the end of the recording. Twelve trials demonstrated a superimposed EMG background response during and after the crush event, with disappearance occurring within 4–8 min. Qualitative histology assessment at the lesion site demonstrated a correspondence between CMAP response and partial sparing of nerve fibers. By using a targeted decline in CMAP amplitude as the endpoint, researchers may be able to produce controlled, brief, and reproducible crush injuries. This model can also be used to test interventions aimed at enhancing subsequent regeneration and behavioral recovery.