Multipoint incremental motor unit number estimation versus amyotrophic lateral sclerosis functional rating scale and the medical research council sum score as an outcome measure in amyotrophic lateral sclerosis

Introduction:

Monitoring the disease progression in amyotrophic lateral sclerosis (ALS) is a challenge due to different rates of progression between patients. Besides clinical methods to monitor disease progression, such as the ALS functional rating scale (ALSFRS) and the medical research council (MRC) sum score, quantitative methods like motor unit number estimation (MUNE) are of interest.

Objective:

The objective of the present study is to evaluate the rate of progression in ALS using multipoint incremental MUNE and to compare MUNE, ALSFRS and MRC sum score at baseline and at 6 months for progression of the disease.

Materials and Methods:

Multipoint incremental MUNE using median nerve, ALS-FRS and MRC sum score was carried out in 29 ALS patients at baseline and then at 6 months.

Results:

Of the 29 ALS patients studied, the mean MUNE at baseline was 21.80 (standard deviation [SD]: 19.46, range 4-73), 15.9 in the spinal onset group (SD: 14.60) and 30.16 (SD: 22.89) in the bulbar onset group. Spinal onset patients had 74.02% of baseline MUNE value while bulbar onset patients had only 24.74% baseline value MUNE at 6 months follow-up (Unpaired t-test, P = 0.001). ALSFRS and MRC sum score showed statistically significant decline (P < 0.001) at 6 months follow-up. MUNE had the highest sensitivity for progression of the disease when compared to the ALS FRS and MRC sum score.

Conclusion:

Multipoint incremental MUNE is a valuable tool for outcome measure in ALS and other diseases characterized by motor unit loss. The rate of decline of multipoint incremental MUNE is more sensitive than that of MRC sum score and ALSFRS-R, when expressed as the percentage change from baseline.     

Sensitivity of electrophysiological tests for upper and lower motor neuron dysfunction in ALS: A six‐month longitudinal study

By following a group of amyotrophic lateral sclerosis (ALS) patients longitudinally using lower motor neuron (LMN) and upper motor neuron (UMN) markers of dysfunction it may be possible to better understand the functional relationships between these motor systems in this disease. We used neurophysiological techniques to follow UMN and LMN dysfunction in a group of 28 patients with ALS, in comparison with the ALS functional rating scale (ALS‐FRS) score and the forced vital capacity (FVC). We used motor unit number estimation (MUNE), compound muscle action potential (CMAP) amplitude, and the Neurophysiological Index (NI) to quantify the LMN disorder, and transcranial motor stimulation to study cortical motor threshold, motor‐evoked response amplitude, central motor conduction time, and cortical silent period (CSP). The patients were studied shortly after diagnosis and then 6 months later, using both abductor digiti minimi muscles (ADM); ADM strength was initially >MRC 3 (Medical Research Council, UK). The NI and MUNE changed more than any other variable. CSP increased by about 30%, a change more marked than the slight increase observed in the cortical motor threshold (9%). The normal increase of CSP after acute muscle fatigue was preserved during disease progression. The CSP increase correlated with the MUNE rate of decay but not to the NI reduction, perhaps because NI includes F‐wave frequency in itscalculation. There was no definite correlation between UMN and LMNdysfunction or progression, but there was a link between CSP and LMN changes in ALS. The CSP may be a useful variable in following UMN dysfunction in clinical practice and in clinical trials. Muscle Nerve, 2010     

Monitoring disease progression using high‐density motor unit number estimation in amyotrophic lateral sclerosis

In amyotrophic lateral sclerosis (ALS), progressive motor neuron loss causes severe weakness. Functional measurements tend to underestimate the underlying pathology because of collateral reinnervation. A more direct marker of lower motor neuron loss is of significant importance. We evaluated high‐density motor unit number estimation (MUNE), as compared with the ALS Functional Rating Scale (ALSFRS) and maximal compound muscle action potential (CMAP) amplitude, for monitoring and classifying disease progression. MUNE showed good reproducibility (intraclass correlation coefficient = 0.86). MUNE showed a significantly greater decrease than the ALSFRS, the Medical Research Council (MRC) scale, and CMAP amplitude. Patients could be stratified into groups with rapidly or slowly progressive disease based on a decrement in MUNE at 4 months from baseline; ALSFRS score at 8 months was significantly lower in the rapidly progressive group. MUNE was sensitive to motor neuron loss early in the disease course when compared to other clinical measures. Stratification of patients based on a decrease in MUNE seems feasible. Muscle Nerve, 2010     

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.     

Brain plasticity in the motor network is correlated with disease progression in amyotrophic lateral sclerosis

Objective: To test the influence of functional cerebral reorganization in amyotrophic lateral sclerosis (ALS) on disease progression. Methods: Nineteen predominantly right‐handed ALS patients and 21 controls underwent clinical evaluation, functional Magnetic Resonance Imaging (fMRI), and diffusion tensor imaging. Patients were clinically re‐evaluated 1 year later and followed until death. For fMRI, subjects executed and imagined a simple hand‐motor task. Between‐group comparisons were performed, and correlations were searched with motor deficit arm Medical Research Council (MRC) score, disease progression ALS Functional Rating Scale (ALSFRS), and survival time. Results: By the MRC score, the hand strength was lowered by 12% in the ALS group predominating on the right side in accordance with an abnormal fractional anisotropy (FA) limited to the left corticospinal tract (37.3% reduction vs. controls P < 0.01). Compared to controls, patients displayed overactivations in the controlateral parietal (P < 0.004) and somatosensory (P < 0.004) cortex and in the ipsilateral parietal (P < 0.01) and somatosensory (P < 0.01) cortex to right‐hand movement. Movement imagination gave similar results while no difference occurred with left‐hand tasks. Stepwise regression analysis corrected for multiple comparisons showed that controlateral parietal activity was inversely correlated with disease progression (R² = 0.43, P = 0.001) and ipsilateral somatosensory activations with the severity of the right‐arm deficit (R² = 0.48, P = 0.001). Conclusions: Cortical Blood Oxygen Level Dependent (BOLD) signal changes occur in the brain of ALS patients during a simple hand‐motor task when the motor deficit is still moderate. It is correlated with the rate of disease progression suggesting that brain functional rearrangement in ALS may have prognostic implications. Hum Brain Mapp 34:2391–2401, 2013. © 2012 Wiley Periodicals, Inc.     

The motor neuron response to SMN1 deficiency in spinal muscular atrophy

Introduction: The purpose of this study was to measure and analyze motor unit number estimation (MUNE) values longitudinally in spinal muscular atrophy (SMA). Methods: Sixty‐two children with SMA types 2 and 3 were observed prospectively for up to 42 months. Longitudinal electrophysiological data were collected, including compound motor action potential (CMAP), single motor unit action potential (SMUP), and MUNE. Results: Significant motor neuron loss and compensatory collateral reinnervation were noted at baseline. Over time, there was a significant mean increase in MUNE (4.92 units/year, P = 0.009), a mean decrease in SMUP amplitude (?6.32 μV/year, P = 0.10), and stable CMAP amplitude. Conclusions: The unexpected longitudinal results differ from findings in amyotrophic lateral sclerosis studies, perhaps indicating that compensatory processes in SMA involve new motor unit development. A better understanding of the mechanisms of motor unit decline and compensation in SMA is important for assessing novel therapeutic strategies and for providing key insights into disease pathophysiology. Muscle Nerve 49 : 636–644, 2014     

Intra-rater reliability of motor unit number estimation and quantitative motor unit analysis in subjects with amyotrophic lateral sclerosis

ObjectivesTo assess the intra-rater reliability of decomposition-enhanced spike-triggered averaging (DE-STA) motor unit number estimation (MUNE) and quantitative motor unit potential analysis in the upper trapezius (UT) and biceps brachii (BB) of subjects with amyotrophic lateral sclerosis (ALS) and to compare the results from the UT to control data.MethodsPatients diagnosed with clinically probable or definite ALS completed the experimental protocol twice with the same evaluator for the UT (n = 10) and BB (n = 9).ResultsIntra-rater reliability for the UT was good for the maximum compound muscle action potential (CMAP) (ICC = 0.88), mean surface-detected motor unit potential (S-MUP) (ICC = 0.87) and MUNE (ICC = 0.88), and for the BB was moderate for maximum CMAP (ICC = 0.61), and excellent for mean S-MUP (ICC = 0.94) and MUNE (ICC = 0.93). A significant difference between tests was found for UT MUNE. Comparing subjects with ALS to control subjects, UT maximum CMAP (p < 0.01) and MUNE (p < 0.001) values were significantly lower, and mean S-MUP values significantly greater (p < 0.05) in subjects with ALS.ConclusionsThis study has demonstrated the ability of the DE-STA MUNE technique to collect highly reliable data from two separate muscle groups and to detect the underlying pathophysiology of the disease.SignificanceThis was the first study to examine the reliability of this technique in subjects with ALS, and demonstrates its potential for future use as an outcome measure in ALS clinical trials and studies of ALS disease severity and natural history.     

Motor unit number index and compound muscle action potential amplitude

ObjectivesMUNIX (motor unit number index), derived from the compound muscle action potential (CMAP) and surface EMG interference pattern (SIP) has become popular as a substitute for motor unit number estimation (MUNE). This study was undertaken to determine why, in recent recordings from amyotrophic lateral sclerosis (ALS) patients and healthy controls, we found that MUNIX values resembled CMAP amplitudes more closely than MUNE values.MethodsThe relationship between MUNIX and CMAP and SIP amplitudes was investigated by a theoretical analysis and by reanalysing the data from the previous study.ResultsTheory indicates that when motor unit potentials overlap extensively, information about motor unit size and number is lost, and MUNIX depends only on CMAP area and power. Accordingly, MUNIX values were found to be sensitive to changes in CMAP amplitude but insensitive to changes in SIP amplitude. The reproducibility of MUNIX measurements in healthy controls was found to depend almost entirely on correlation with CMAP properties.ConclusionsMUNIX gives misleading information about motor unit numbers in healthy controls, and provides little information about loss of motor units in ALS patients beyond that given by simple CMAP amplitude measurements.SignificanceMUNIX should not be interpreted as a MUNE method.     

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.     

Pattern difference of dissociated hand muscle atrophy in amyotrophic lateral sclerosis and variants

Introduction: Split hand is considered to be a specific feature of amyotrophic lateral sclerosis (ALS). Methods: We evaluated the pattern difference of intrinsic hand muscles of upper limb‐onset ALS (UL‐ALS), upper limb‐onset progressive muscular atrophy (UL‐PMA), brachial amyotrophic diplegia (BAD), and Hirayama disease (HD) by measuring objective electrophysiological markers. Results: The abductor digiti minimi (ADM)/abductor pollicis brevis (APB) compound muscle action potential (CMAP) amplitude ratio was significantly higher in UL‐ALS than other variants, but a considerable proportion of UL‐ALS cases had an amplitude ratio in the range of other variants. Absent APB CMAP and abnormally high ADM/APB CMAP amplitude ratio (≥4) occurred only with UL‐ALS. Conversely, an absent ADM CMAP was identified only in UL‐PMA and BAD. Conclusions: The absolute ADM/APB CMAP amplitude ratio was not specific for ALS; however, several findings from simple electrophysiological measurements may help predict prognosis in patients with motor neuron diseases and may be early diagnostic markers for ALS. Muscle Nerve 51: 333–337, 2015     

MOTOR UNIT NUMBER ESTIMATION (MUNE) AS A QUANTITATIVE MEASURE OF DISEASE PROGRESSION AND MOTOR UNIT REORGANIZATION IN AMYOTROPHIC LATERAL SCLEROSIS

Motor Unit Number Estimation (MUNE), a technique allowing to estimate the number of functioning Motor Units (MU) in single muscles, was used to score the disease's severity and progression rate in a group of 58 patients with Amyotrophic Lateral Sclerosis (ALS). All patients underwent MUNE in the abductor digiti minimi (ADM) muscle during the diagnostic work-up (T0), after three (T1) and six (T2) months. A significant loss [p < .001] of MU and a decrease [p < .001] of the maximal M wave area at T0 was found, whereas mean step area was increased [p < .001]. During the follow-up (T1 and T2), MU loss continued, maximal M wave decreased, and mean step area increased significantly. The results confirm that MUNE is a suitable tool to quantify the pathological changes in MU in patients with ALS.     

Influence of needle electrode depth on DE‐STA motor unit number estimation

Introduction: To assess a potential source of technique‐associated error, we evaluated the influence of needle electrode depth on decomposition‐enhanced spike‐triggered averaging (DE‐STA) motor unit number estimation (MUNE) and quantitative motor unit analysis in the upper trapezius (UT). Methods: The DE‐STA MUNE protocol was performed at superficial, intermediate, and deep needle electrode depths in 18 control subjects. Results: Mean surface‐detected motor unit potential amplitudes were significantly smaller for intermediate versus superficial (P < 0.05), deep versus superficial (P < 0.001), and deep versus intermediate (P < 0.05). MUNE was significantly larger for deep versus superficial (P < 0.001), with statistical trends toward larger MUNE values at greater depths for the remaining comparisons. No significant differences were found among needle electrode depths for quantitative motor unit potential parameters. Conclusions: These results demonstrate the important influence of needle electrode depth on DE‐STA MUNE in the UT. Suggestions are made for improved standardization of the protocol. Muscle Nerve 50: 587–592, 2014     

Motor unit number estimation,isometric strength,and electromyographic measures in amyotrophic lateral sclerosis

Pathologic progression in amyotrophic lateral sclerosis (ALS) results from motor neuron death, while the clinical expression also reflects the compensatory effects of collateral reinnervation consequent to lower motor neuron loss. In a cross-sectional study of ALS subjects, we made comparisons between motor unit number estimation (MUNE) values and several measures reflecting collateral reinnervation, including isometric strength, compound muscle action potential (CMAP) amplitude, surface motor unit action potential (S-MUAP) amplitude, fiber density (FD), macro-EMG potential amplitude, turns-to-amplitude (T/A) ratio, and amplitude and recruitment pattern of low threshold voluntary motor units in elbow flexor muscles. Before comparisons were made, testretest reproducibility of these measures was assessed in ALS subjects, and is highest for isometric strength, and lower but similar for EMG measures. When the effects of multiple comparisons are considered, borderline significant correlations are found between MUNE values and isometric strength. Neither MUNE values nor isometric strength are significantly correlated with macro-EMG amplitude, FD, T/A ratio, or amplitude and recruitment rate of low threshold voluntary motor units. There are significant correlations of CMAP and S-MUAP with MUNE values, but these are statistical artifacts with no independent interpretation. We conclude that collateral reinnervation prevents isometric strength and EMG measures from accurately reflecting lower motor neuron death in ALS. MUNE measurements are better suited to provide insight into the true natural history of the disease process and may be clinically useful to follow progression and response in drug trials. © 1993 John Wiley & Sons, Inc.     

Cerebrospinal fluid and serum antibodies against neurofilaments in patients with amyotrophic lateral sclerosis

Background: The aim of the study was to assess autoimmune involvement in amyotrophic lateral sclerosis (ALS). Methods: We measured IgG antibodies against light (NFL) and medium (NFM) subunits of neurofilaments using ELISA in paired cerebrospinal fluid (CSF) and serum samples from 38 ALS patients and 20 controls. Results: Serum levels of anti‐NFL were higher in ALS patients than in controls (P < 0.005). Serum anti‐NFL antibodies and intrathecal anti‐NFM antibodies were related to patient disability (serum anti‐NFL: P < 0.05; intrathecal anti‐NFM: P < 0.05). Anti‐NFL levels were significantly correlated with anti‐NFM levels in ALS (P < 0.001) and the control group (P < 0.0001) in the CSF, but not in serum. Anti‐NFL and anti‐NFM antibodies significantly correlated between serum and CSF in the ALS group (anti‐NFL: P < 0.0001; anti‐NFM: P < 0.001) and in the control group (anti‐NFL: P < 0.05; anti‐NFM: P < 0.05). Conclusions: Autoimmune humoral response to neurocytoskeletal proteins is associated with ALS.     

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.     

Evaluation of spinal and bulbar muscular atrophy by the clustering index method

Introduction: A reliable electrophysiological marker for clinical trials is increasingly needed in spinal and bulbar muscular atrophy (SBMA). We previously developed a quantitative analysis method for surface electromyography (SEMG), the clustering index (CI) method. Our purpose was to test the utility of the CI method for evaluating lower motor neuron involvement in SBMA patients. Methods: Subjects included 29 SBMA patients and 27 healthy controls. The recording electrode was placed over the abductor digiti minimi (ADM) muscle with a proximal reference. The Z‐score, based on the CI method, was compared with compound muscle action potential (CMAP) amplitude and motor unit number estimation (MUNE), with regard to sensitivity. Results: The Z‐scores of the CI method, CMAP amplitude, and MUNE were abnormal in 100%, 72%, and 93% of the patients, respectively. Interrater reliability of the CI method was sufficiently high. Conclusion: The CI method is promising as a non‐invasive electrophysiological marker in SBMA. Muscle Nerve, 2011     

Estimating motor unit numbers from a CMAP scan

Introduction: Compound muscle action potential (CMAP) scans are detailed stimulus‐response curves which provide information about motor unit properties in neuromuscular disorders. This study assessed a method of automatic motor unit number estimation (MUNE) from 5‐min CMAP scans. Methods: A preliminary model, derived from the variance and slope of the scan, is refined to fit the CMAP scan more closely. The method was tested by application to 60 simulated scans, generated from between 5 and 160 motor unit potentials. Results: The fitting procedure took an average of 1.5 min on a standard personal computer. Small unit numbers (5–20) were on average correctly estimated, but large unit numbers (>40) were slightly underestimated. Overall, the absolute MUNE error averaged 6.9%. Conclusions: This new MUNE method takes all excitable motor units into account and provides realistic estimates of unit numbers over the range 5 to 160. Validation as a clinical tool awaits further study. Muscle Nerve 53 : 889–896, 2016     

The utility of motor unit number estimation methods versus quantitative motor unit potential analysis in diagnosis of ALS

Objective

To compare the diagnostic utility of motor unit number estimation (MUNE) methods to motor unit potential (MUP) analysis in amyotrophic lateral sclerosis (ALS).

Compound muscle action potential and motor function in children with spinal muscular atrophy

Reliable outcome measures that reflect the underlying disease process and correlate with motor function in children with SMA are needed for clinical trials. Maximum ulnar compound muscle action potential (CMAP) data were collected at two visits over a 4–6‐week period in children with SMA types II and III, 2–17 years of age, at four academic centers. Primary functional outcome measures included the Modified Hammersmith Functional Motor Scale (MHFMS) and MHFMS‐Extend. CMAP negative peak amplitude and area showed excellent discrimination between the ambulatory and non‐ambulatory SMA cohorts (ROC = 0.88). CMAP had excellent test–retest reliability (ICC = 0.96–0.97, n = 64) and moderate to strong correlation with the MHFMS and MHFMS‐Extend (r = 0.61–0.73, n = 68, P < 0.001). Maximum ulnar CMAP amplitude and area is a feasible, valid, and reliable outcome measure for use in pediatric multicenter clinical trials in SMA. CMAP correlates well with motor function and has potential value as a relevant surrogate for disease status. Muscle Nerve, 2010     

肌萎缩侧索硬化患者膈神经传导的电生理分析

目的 通过分析肌萎缩侧索硬化(Amyotrophic Lateral Sclerosis,ALS)患者膈神经传导检测,并结合其它神经电生理资料,为该病提供更深入的认识,进一步指导临床诊疗。方法 研究范围为武汉大学人民医院2014年1月-2021年12月就诊的ALS患者共88例,收集患者的一般资料、主要症状及体征、肌萎缩侧索硬化改良量表(ALSFRS-R)评分、运动神经传导检测中的复合肌肉动作电位(CMAP)波幅和远端运动潜伏期(DML)等指标。结果(1)运动神经传导检测中CMAP波幅降低192条(43.6%),膈神经波幅异常率为35.2%; 远端潜伏期延长116条(26.4%),膈神经DML异常率为77.3%;(2)膈神经DML在性别方面存在明显差异(P<0.01);(3)ALSFRS-R评分与膈神经、尺神经、正中神经、腓总神经、胫神经的CMAP波幅呈正相关(r=0.393,P<0.01; r=0.375,P<0.01; r=0.413,P<0.01; r=0.251,P<0.05; r=0.442,P<0.01);(4)膈神经DML及CMAP波幅在起病部位方面存在明显差异(P<0.05; P<0.05);(5)膈神经DML在判断病情中度和轻度之间的最佳界点为9.095 ms,敏感性为85.7%,特异性为80.2%。结论 ALS患者的运动神经传导可表现异常,CMAP波幅下降占比较大,但膈神经中潜伏期延长比CMAP波幅降低更多见。膈神经传导检测存在一定程度的性别差异。行运动神经传导检测时多条神经CMAP波幅变化可反映ALS患者病情严重程度。膈神经潜伏期变化可更敏感地反映ALS的病情严重程度,以期指导临床诊断与治疗。