Intra- and inter-rater reliability of motor unit number estimation and quantitative motor unit analysis in the upper trapezius

Objective

To collect normative data and assess the intra- and inter-rater reliability of decomposition-enhanced spike-triggered averaging (DE-STA) motor unit number estimation (MUNE) and quantitative MU analysis obtained using decomposition-based quantitative electromyography (DQEMG) in the upper trapezius (UT).

Methods

In 10 control subjects, the experimental protocol was performed twice by the same examiner, and once by a second examiner.

Results

Mean MUNE values were 339 ± 121 (rater 1a), 320 ± 131 (rater 1b), and 262 ± 115 (rater 2) MUs. Intra- and inter-rater reliability was good for maximum CMAP (ICC = 0.77 and 0.79, respectively) and moderate for MUNE (ICC = 0.69 and 0.73, respectively), with poor inter-rater reliability for mean S-MUP (ICC = 0.42). Significant differences between rater 1a and 2 were found for mean S-MUP (p = 0.014) and MUNE (p = 0.002), and moderate to good levels of reliability found for quantitative needle-detected MUP parameters.

Conclusions

Various components of the protocol may have contributed to mean S-MUP variability, and may require particular attention in a large, proximal muscle like the UT.

Significance

This study has established preliminary data using DQEMG in a novel muscle which may be relevant to study in patients with ALS.     

CMAP scan discontinuities: Automated detection and relation to motor unit loss

ObjectiveTo evaluate an automated method that extracts motor unit (MU) information from the CMAP scan, a high-detail stimulus–response curve recorded with surface EMG. Discontinuities in the CMAP scan are hypothesized to result from MU loss and reinnervation.MethodsWe introduce the parameter D50 to quantify CMAP scan discontinuities. D50 was compared with a previously developed manual score in 253 CMAP scans and with a simultaneously obtained motor unit number estimate (MUNE) in 173 CMAP scans. The effect of MU loss on D50 was determined with a simulation model.ResultsWe found a high agreement (sensitivity = 86.8%, specificity = 96.6%) between D50 and the manual score. D50 and MUNE were significantly correlated below 80 MUs (r = 0.65, n = 68, p < 0.001), but not when MUNE was larger than 120 MUs (r = 0.23, n = 59, p = 0.08).ConclusionsDiscontinuities in the CMAP scan as expressed by a decreased D50 are related to significant MU loss. The determination of D50 is objective, quantitative, and less time-consuming than both manual scoring and many existing MUNE methods.SignificanceD50 is potentially useful to monitor neurogenic disorders and moderate to severe MU loss.     

Reproducibility,and sensitivity to motor unit loss in amyotrophic lateral sclerosis,of a novel MUNE method: MScanFit MUNE

ObjectiveTo examine inter- and intra-rater reproducibility and sensitivity to motor unit loss of a novel motor unit number estimation (MUNE) method, MScanFit MUNE (MScan), compared to two traditional MUNE methods; Multiple point stimulation MUNE (MPS) and Motor Unit Number Index (MUNIX).MethodsTwenty-two ALS patients and 20 sex- and age-matched healthy controls were included. MPS, MUNIX, and MScan were performed twice each by two blinded physicians. Reproducibility of MUNE values was assessed by coefficient of variation (CV) and intra class correlation coefficient (ICC). Ability to detect motor unit loss was assessed by ROC curves and area under the curve (AUC). The times taken for each of the methods were recorded.ResultsMScan was more reproducible than MPS and MUNIX both between and within operators. The mean CV for MScan (12.3%) was significantly lower than for MPS (24.7%) or MUNIX (21.5%). All methods had ICC > 0.94. MScan and Munix were significantly quicker to perform than MPS (6.3 m vs. 13.2 m). MScan (AUC = 0.930) and MPS (AUC = 0.899) were significantly better at discriminating between patients and healthy controls than MUNIX (AUC = 0.831).ConclusionsMScan was more consistent than MPS or MUNIX and better at distinguishing ALS patients from healthy subjects.SignificanceMScan may improve detection and assessment of motor unit loss.     

Motor unit number index (MUNIX) versus motor unit number estimation (MUNE): a direct comparison in a longitudinal study of ALS patients

ObjectiveTo evaluate how the motor unit number index (MUNIX) is related to high-density motor unit number estimation (HD-MUNE) in healthy controls and patients with amyotrophic lateral sclerosis (ALS).MethodsBoth MUNIX and HD-MUNE were performed on the thenar muscles in 18 ALS patients and 24 healthy controls. Patients were measured at baseline, within 2 weeks, and after 4 and 8 months. Clinical evaluation included Medical Research Council (MRC) scale and the ALS functional rating scale (ALSFRS).ResultsThere was a significant positive correlation between MUNE and MUNIX values in ALS patients (r = 0.49 at baseline; r = 0.56 at 4 months; r = 0.56 at 8 months, all p < 0.05), but not in healthy controls. After 8 months, both MUNE and MUNIX values of the ALS patients decreased significantly more compared to MRC scale, ALS functional rating scale (ALSFRS) and compound muscle action potential (CMAP) (p < 0.05). There was no significant difference in relative decline of MUNIX and HD-MUNE values.ConclusionsIn ALS patients, MUNIX and HD-MUNE are significantly correlated. MUNIX has an almost equivalent potential in detecting motor neuron loss compared to HD-MUNE.SignificanceMUNIX could serve as a reliable and sensitive marker for monitoring disease progression in ALS.     

MUNIX and incremental stimulation MUNE in ALS patients and control subjects

ObjectiveThis study compares the new Motor Unit Number Estimation (MUNE) technique, MUNIX, with the more common incremental stimulation MUNE (IS-MUNE) with respect to reproducibility in healthy subjects and as potential biomarker of disease progression in patients with ALS.MethodsThirteen ALS patients and 48 control subjects were prospectively investigated – both groups were studied with MUNIX and IS-MUNE applied on the abductor digiti minimi (ADM) muscle. Additional retest was performed on 14 control subjects. Follow-up tests were carried out on 6 patients. The analysis included measures of reproducibility (Intraclass Correlation Coefficient (ICC)) and diagnostic performance (Receiver Operating Characteristic (ROC) analysis).ResultsTest–retest reproducibility was low to moderate for MUNIX and IS-MUNE (ICC = 0.38 and 0.56, respectively). Repeated MUNIX and IS-MUNE measurements on the same subject had a mean percentage difference (MPD) of 20% and 46%, respectively (p = 0.039). In the control group, the coefficient of variation was markedly lower for MUNIX than for IS-MUNE (26% and 44%, respectively, p < 0.0005). In ALS patients MUNIX had a notably better responsiveness in follow-up than IS-MUNE (percent change per month, 9.4 versus 5.6, p = 0.046). ROC analysis suggested similar diagnostic accuracy of both tests.ConclusionsMUNIX is a useful MUNE indicator when assessing progression of lower motor neuron affection in ALS. Furthermore, MUNIX displayed lower intrasubject variability, but no evident better diagnostic yield compared with IS-MUNE.SignificanceThis study has established comparative assessment of MUNIX and IS-MUNE performance in test–retest setting and as diagnostic tests on a distal muscle in ALS patients.     

Inter-rater reliability of motor unit number estimates and quantitative motor unit analysis in the tibialis anterior muscle

ObjectiveTo establish the inter-rater reliability of decomposition-based quantitative electromyography (DQEMG) derived motor unit number estimates (MUNEs) and quantitative motor unit (MU) analysis.MethodsUsing DQEMG, two examiners independently obtained a sample of needle and surface-detected motor unit potentials (MUPs) from the tibialis anterior muscle from 10 subjects. Coupled with a maximal M wave, surface-detected MUPs were used to derive a MUNE for each subject and each examiner. Additionally, size-related parameters of the individual MUs were obtained following quantitative MUP analysis.ResultsTest–retest MUNE values were similar with high reliability observed between examiners (ICC = 0.87). Additionally, MUNE variability from test–retest as quantified by a 95% confidence interval was relatively low ($\pm 28$ MUs). Lastly, quantitative data pertaining to MU size, complexity and firing rate were similar between examiners.ConclusionMUNEs and quantitative MU data can be obtained with high reliability by two independent examiners using DQEMG.SignificanceEstablishing the inter-rater reliability of MUNEs and quantitative MU analysis using DQEMG is central to the clinical applicability of the technique. In addition to assessing response to treatments over time, multiple clinicians may be involved in the longitudinal assessment of the MU pool of individuals with disorders of the central or peripheral nervous system.     

Assessment of motor unit loss in patients with spinal muscular atrophy

ObjectiveTo assess motor unit (MU) changes in patients with spinal muscular atrophy (SMA) using compound muscle action potential (CMAP) scans.MethodsWe performed CMAP scan recordings in median nerves of 24 treatment-naïve patients (median age 39; range 12–75 years) with SMA types 2–4. From each scan, we determined maximum CMAP amplitude (CMAP_max), a motor unit number estimate (MUNE), and D50 which quantifies the largest discontinuities within CMAP scans.ResultsMedian CMAP_max was 8.1 mV (range 0.9–14.6 mV), MUNE was 29 (range 6–131), and D50 was 25 (range 2–57). We found a reduced D50 (<25) in patients with normal CMAP_max (n = 12), indicating MU loss and enlarged MUs due to reinnervation. Lower D50 values were associated with decreased MUNE (P < 0.001, r = 0.68, n = 43). CMAP_max, MUNE and D50 values differed between SMA types (P < 0.001). Lower motor function scores were related to patients with lower CMAP_max, MUNE and D50 values (P < 0.001).ConclusionsThe CMAP scan is an easily applicable technique that is superior to routine assessment of CMAP_max in SMA.SignificanceThe detection of pathological MU changes across the spectrum of SMA may provide important biomarkers for evaluating disease course and monitoring treatment efficacy.     

Estimating motor unit discharge patterns from high-density surface electromyogram

ObjectiveWe systematically tested the capability of the Convolution Kernel Compensation (CKC) method to identify motor unit (MU) discharge patterns from the simulated and experimental surface electromyogram (sEMG) during low-force contractions.MethodssEMG was detected with a grid of 13 × 5 electrodes. In simulated signals with 20 dB signal-to-noise ratio, 11 ± 3 out of 63 concurrently active MUs were identified with sensitivity >95% in the estimation of their discharge times. In experimental signals recorded at 0–10% of the maximal force, the discharge patterns of (range) 11–19 MUs (abductor pollicis; n = 8 subjects), 9–17 MUs (biceps brachii; n = 2), 7–11 MUs (upper trapezius; n = 2), and 6–10 MUs (vastus lateralis; n = 2) were identified. In the abductor digiti minimi muscle of one subject, the decomposition results from concurrently recorded sEMG and intramuscular EMG (iEMG) were compared; the two approaches agreed on 98 ± 1% of MU discharges.ConclusionIt is possible to identify the discharge patterns of several MUs during low-force contractions from high-density sEMG.SignificancesEMG can be used for the analysis of individual MUs when the application of needles is not desirable or in combination with iEMG to increase the number of sampled MUs.     

Assessment of swallowing in motor neuron disease and Asidan/SCA36 patients with new methods

BackgroundWe report on a unique complication of cerebellar ataxia and motor neuron disease named Asidan/SCA36 with a high frequency of tongue atrophy. We aimed to elucidate dysphagia in amyotrophic lateral sclerosis (ALS) and spinal, bulbar muscular atrophy (SBMA), and Asidan/SCA36 patients with new methods.MethodsPatients diagnosed with ALS (n = 20), SBMA (n = 6), and Asidan (n = 12) were included. A videofluoroscopic swallow study (VFS), an assessment of maximal tongue pressure (MTP), and impedance pharyngography (IPG) were applied.ResultsThe frequencies of VFS abnormalities were 70%, 50%, and 33% in ALS, SBMA, and Asidan/SCA36, respectively. Compared with control subjects (31.6 ± 6.3 kPa, mean ± SD), MTP was significantly decreased in ALS patients and SBMA patients, but was relatively preserved in Asidan patients. ALS patients performed more swallowing actions (Ns) detected by IPG than did control subjects, but SBMA and Asidan/SCA36 patients performed similar Ns to control subjects.ConclusionsVFS showed a higher frequency of swallowing abnormalities in ALS patients. MTP and IPG measurements showed the most severe involvement in ALS patients and a relatively preserved swallowing function in SBMA and Asidan/SCA36 patients.     

Motor unit number estimation in the quantitative assessment of severity and progression of motor unit loss in Hirayama disease

Objective

To investigate motor unit number estimation (MUNE) as a method to quantitatively evaluate severity and progression of motor unit loss in Hirayama disease (HD).

Split-hand index for the diagnosis of amyotrophic lateral sclerosis

ObjectivePreferential wasting of the thenar group of muscles, the split hand sign, appears to be a specific feature of ALS. The present study developed a novel split-hand index (SI) and assessed its diagnostic utility in ALS.MethodsOne hundred and seventy consecutive patients with neuromuscular symptoms (44 ALS, 126 patients with other neuromuscular disorders) were prospectively recruited according to standards for reporting of diagnostic accuracy (STARD) criteria. The SI was derived by dividing the product of the compound muscle action potential (CMAP) amplitude recorded over the first dorsal interosseous and abductor pollicis brevis by the CMAP amplitude recorded over the abductor digiti minimi.ResultsThe SI was significantly reduced in ALS patients (ALS 3.5 ± 0.6; patients with other neuromuscular disorders 9.1 ± 0.3, P < 0.0001), particularly in limb-onset ALS (2.3 ± 0.5, P < 0.0001). Receiver operating characteristic curve analysis indicated that SI reliably differentiated ALS from patients with other neuromuscular disorders (area under curve ALS 0.83, P < 0.0001) with an optimal SI cut-off value of 5.2 exhibiting a sensitivity of 74% and specificity 80%.ConclusionsThe split-hand index robustly differentiates ALS from mimic disorders.SignificanceThe split-hand index is a simple measure that could be utilized in a standard neurophysiology setting. A reduction in SI distinguishes ALS from mimic disorders, potentially facilitating an earlier diagnosis of ALS.     

Comparison between the degree of motor unit short-term synchronization and recurrence quantification analysis of the surface EMG in two human muscles

ObjectiveTo verify if non-linear recurrence analysis of the surface EMG is a suitable tool for assessing motor unit short-term synchronization.MethodsSurface and intramuscular EMG signals were recorded from the abductor digiti minimi and vastus medialis muscles of 12 and 10 healthy men, respectively, during isometric contractions. In the abductor digiti minimi, EMG signals were additionally recorded after a contraction sustained for 1 min at 50% of the maximal force. In both muscles, percent of determinism (%DET) was estimated from the surface EMG and common input strength (CIS) index was computed from motor unit recordings.ResultsFor both muscles, CIS did not correlate with %DET (abductor digiti minimi: R² = 0.11, P = 0.12; vastus medialis: R² = 0.04, P = 0.56). Although the values of CIS for the vastus medialis were lower than those of the abductor digiti minimi (P < 0.001), the %DET values did not differ between the two muscles (71.6 ± 5.5% vs 66.9 ± 8.7%; P = 0.12).ConclusionThe variable %DET extracted from the surface EMG is a poor indicator of the degree of motor unit short-term synchronization.SignificanceThe study provides a systematic evaluation of a technique previously proposed for the estimation of a clinically relevant characteristic of motor unit behavior.     

Implicit and explicit motor learning: Application to children with Autism Spectrum Disorder (ASD)

Aims and objectivesThis study aims to determine whether children with Autism Spectrum Disorder (ASD) are capable of learning a motor skill both implicitly and explicitly.MethodsIn the present study, 30 boys with ASD, aged 7–11 with IQ average of 81.2, were compared with 32 typical IQ- and age-matched boys on their performance on a serial reaction time task (SRTT). Children were grouped by ASD and typical children and by implicit and explicit learning groups for the SRTT.ResultsImplicit motor learning occurred in both children with ASD (p = .02) and typical children (p = .01). There were no significant differences between groups (p = .39). However, explicit motor learning was only observed in typical children (p = .01) not children with ASD (p = .40). There was a significant difference between groups for explicit learning (p = .01).DiscussionThe results of our study showed that implicit motor learning is not affected in children with ASD. Implications for implicit and explicit learning are applied to the CO-OP approach of motor learning with children with ASD.     

Differentiation between uniform and non-uniform motor nerve conduction slowing

ObjectiveDemyelination may cause a uniform reduction of the conduction velocity of all fibres of a peripheral nerve segment, or may affect only certain nerve fibres in a non-uniform way while sparing others. This study was done to improve the detection of non-uniform conduction slowing by using the high-frequency attenuation (HFA) method.MethodsNerve conduction data from patients with early inflammatory demyelinating neuropathy (non-uniform demyelination, n = 20), hereditary neuropathy (uniform demyelination, n = 9), motor neuron disease (axon loss, n = 20), and from healthy control subjects (n = 20) were analysed.ResultsHFA, compound muscle action potential (CMAP) amplitude decay, and F-wave chronodispersion correlated significantly. Among these variables both HFA and amplitude decay most sensitively identified non-uniform demyelination (35%). In the patients with uniform demyelination, the most frequent finding was a reduced nerve conduction velocity (NCV) (100%). The most specific marker of non-uniform demyelination was HFA. For uniform demyelination it was NCV.ConclusionsThe pattern of correlations between the variables studied confirms that NCV and F-min are indicators of uniform conduction slowing. HFA, amplitude decay, and F-wave chronodispersion indicate non-uniform conduction slowing, for which HFA is both sensitive and specific.SignificanceThe HFA method improves both the diagnostic sensitivity and specificity of nerve conduction studies in patients with non-uniform demyelination.     

Changes of the phrenic nerve motor response in amyotrophic lateral sclerosis: Longitudinal study

ObjectivePhrenic nerve motor amplitude (Diaphr Ampl) is predictive of hypoventilation in amyotrophic lateral sclerosis (ALS). We aimed to evaluate its change over disease course and to correlate it to other measurements.MethodsForty-nine unselected patients (35 men, 13 bulbar-onset, 56.5 ± 8.9 years) with definitive or probable ALS were included. They were evaluated at entry (time 0) and 4–6 months (5.2 ± 1.0) later (time 1) with: functional ALS rating scale (ALS-FRS) and respiratory subscore (ALS-FRSr); forced vital capacity (FVC); maximal inspiratory pressure (MIP); mean O₂ saturation overnight (SpO₂mean); sniff maximal inspiratory pressure (SNIP); Diaphr Ampl and mean amplitude of the ulnar nerve response (ADM Ampl).ResultsALS-FRS, ALS-FRSr, Diaphr Ampl, FVC, SNIP, ADM Ampl (p < 0.01) and SpO₂mean (p < 0.05) declined significantly. MIP did not change significantly (p = 0.203). Coefficient of variation was similar for FVC, Diaphr Ampl, ADM Ampl and ALS-FRS but higher for SNIP. The percentage of change for Diaphr Ampl was significantly correlated to FVC and SNIP, but not to ADM Ampl or ALS-FRS.ConclusionsDiaphr Ampl decreased significantly in a short period of time and its change is correlated to other respiratory tests. This test can be useful in patients with marked facial weakness or uncooperative.SignificanceDiaphr Ampl is useful to monitor respiratory function in ALS patients and can be applied in clinical trials.     

Early motor development of children with a congenital cytomegalovirus infection

BackgroundCongenital cytomegalovirus (cCMV) infection is the most important etiology of non-hereditary childhood hearing loss and an important cause of neurodevelopmental delay. The current study aimed to investigate the early motor development of symptomatic and asymptomatic cCMV infected children with and without sensorineural hearing loss (SNHL).MethodsSixty-four children with a cCMV infection, without cerebral palsy, were compared to a control group of 107 normal hearing children. They were assessed around the ages of 6, 12, and 24 months with the Peabody Developmental Motor Scales-2 (PDMS-2), Alberta Infant Motor Scales (AIMS), and Ghent Developmental Balance Test (GDBT). The cCMV infected children were subdivided into a symptomatic (n = 26) and asymptomatic cCMV group (n = 38) but also into a cCMV group with SNHL (n = 19) and without SNHL (n = 45).ResultsSymptomatic cCMV infected children and cCMV infected children with SNHL performed significantly weaker for all gross motor outcome measures.ConclusionA congenital CMV infection is a risk factor for a delay in the early motor development. Follow-up will be necessary to gain insight into the exact cause of this motor delay and to define the predictive value of early motor assessment of cCMV infected children.     

Modulation of interhemispheric activation balance in motor-related areas of stroke patients with motor recovery: Systematic review and meta-analysis of fMRI studies

BackgroundFunctional magnetic resonance imaging (fMRI) studies suggest that stroke-induced motor deficits are associated with an interhemispheric imbalance of motor activation. This meta-analysis aims to determine the changes of interhemispheric activation balance (IHAB) in motor-related cortices along with post-stroke motor recovery.MethodsWe searched PubMed for fMRI studies that investigated IHAB in stroke patients with motor recovery. Laterality indexes (LIs, (ipsilesional activation − contralesional activation)/(ipsilesional activation + contralesional activation)) before and after motor improvement were extracted as the outcome measures of IHAB. Data were synthesized by calculating standardized mean difference (SMD, Hedges’ adjusted g) with 95% confidence intervals (CI).ResultsAfter the rejection of 459 studies, 22 trials fulfilled the inclusion criteria and were included in the systematic review and meta-analysis. The LIs of sensorimotor cortex (SMC, 22 trials, 195 subjects), premotor cortex (PMC, 12 trials, 93 subjects), supplementary motor area (SMA, 12 trials, 92 subjects), and cerebellum (CB, 4 trials, 31 subjects) were assessed. Studies sampling from stroke patients with motor improvement showed positive changes of LI in SMC (SMD, 0.71; 95% CI, 0.41–1.01; P < 0.00001) and PMC (SMD, 0.68; 95% CI, 0.36–1.00; P < 0.0001), but not in SMA (SMD, 0.07; 95% CI, −0.62 to 0.75; P = 0.85) and CB (SMD, −0.17; 95% CI, −1.52 to 1.19, P = 0.81). Studies involving stroke patients with poor motor recovery showed non-significant changes in all of the four motor-related cortices (P > 0.05).ConclusionsThis meta-analysis suggests that along with good motor recovery of stroke patients, the IHAB is up-regulated in SMC and PMC, but not significantly changed in SMA and CB. Because of the limited data, further studies are needed to verify the findings.     

Predictors and patterns of insomnia symptoms in OSA before and after PAP therapy

ObjectiveIdentify factors that predict improvement versus persistence of insomnia symptoms following treatment of obstructive sleep apnea (OSA) with positive airway pressure (PAP) therapy.MethodsArchival data from 68 PAP-treated sleep apnea patients aged 25–83 were analyzed using nonparametric tests and stepwise regression to assess the relationships between insomnia symptoms, multiple OSA variables, and PAP use over time.ResultsPretreatment insomnia symptom severity (ISS; b = −0.72, p < 0.001), PAP average use (b = −0.01, p = 0.01) and respiratory disturbance index (RDI; b = −0.02, p = 0.03) predict change in insomnia following PAP therapy. Forty-five percent (24/53) of the subjects with moderate to severe insomnia at pretreatment reported no/mild symptoms after PAP therapy and were considered improved. Improved subjects had lower pretreatment ISS (p < 0.001), higher RDI (p = 0.01), and higher average PAP use (p < 0.035) than subjects with persistent insomnia. Number of medications and comorbidities were similar between improved and persistent groups. New onset of insomnia symptoms occurred in 13% (2/15) of the patients with no/mild pretreatment insomnia.ConclusionsAlthough ISS declines following PAP treatment, 55% of OSA patients have persistent moderate to severe symptoms despite treatment. More severe OSA is linked to higher likelihood of insomnia improvement and the effect of PAP therapy on insomnia may be mediated by OSA severity. Persistent insomnia is unrelated to medication use or comorbidities and may represent an independent, self-sustaining disorder requiring targeted intervention.     

Incremento de las citoquinas proteína quimiotáctica de monocitos-1 (MCP-1) y proteína inflamatoria macrofágica-1β (MIP-1β) en líquido cefalorraquídeo de pacientes con esclerosis lateral amiotrófica

IntroductionNeuroinflammation has recently been described in amyotrophic lateral sclerosis (ALS). However, the precise role of such proinflammatory cytokines as monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1β (MIP-1β) in ALS has not yet been determined. In this study, we determined cerebrospinal fluid (CSF) MCP-1 and MIP-1β levels and assessed their association with the duration and severity of ALS.MethodsConcentrations of MCP-1 and MIP-1β were determined in the CSF of 77 patients diagnosed with ALS and 13 controls. Cytokine levels were analysed in relation to ALS duration (< 12 months vs. > 12 months) and severity (< 30 points vs. > 30 points on the ALS Functional Rating Scale administered at hospital admission).ResultsHigher CSF MIP-1β (10.68 pg/mL vs. 4.69 pg/mL, P < .0001) and MCP-1 (234.89 pg/mL vs. 160.95 pg/mL, P = .011) levels were found in the 77 patients with ALS compared to controls. There were no differences in levels of either cytokine in relation to disease duration or severity. However, we did observe a significant positive correlation between MIP-1β and MCP-1 in patients with ALS.ConclusionsThe increase in MIP-1β and MCP-1 levels suggests that these cytokines may have a synergistic effect on ALS pathogenesis. However, in our cohort, no association was found with either the duration or the clinical severity of the disease.     

Advancing disease monitoring of amyotrophic lateral sclerosis with the compound muscle action potential scan

ObjectiveTo determine which compound muscle action potential (CMAP) scan-derived electrophysiological markers are most sensitive for monitoring disease progression in amyotrophic lateral sclerosis (ALS), and whether they hold value for clinical trials.MethodsWe used four independent patient cohorts to assess longitudinal patterns of a comprehensive set of electrophysiological markers including their association with the ALS functional rating scale (ALSFRS-R). Results were translated to trial sample size requirements.ResultsIn 65 patients, 225 thenar CMAP scan recordings were obtained. Electrophysiological markers showed extensive variation in their longitudinal trajectories. Expressed as standard deviations per month, motor unit number estimation (MUNE) values declined by 0.09 (CI 0.07–0.12), D50, a measure that quantifies CMAP scan discontinuities, declined by 0.09 (CI 0.06–0.13) and maximum CMAP by 0.05 (CI 0.03–0.08). ALSFRS-R declined fastest (0.12, CI 0.08 – 0.15), however the between-patient variability was larger compared to electrophysiological markers, resulting in larger sample sizes. MUNE reduced the sample size by 19.1% (n = 388 vs n = 314) for a 6-month study compared to the ALSFRS-R.ConclusionsCMAP scan-derived markers show promise in monitoring disease progression in ALS patients, where MUNE may be its most suitable derivate.SignificanceMUNE may increase clinical trial efficiency compared to clinical endpoints.