Effect of changing data collection parameters on statistical motor unit number estimates

The effect of number of samples and selection of data for analysis on the calculation of surface motor unit potential (SMUP) size in the statistical method of motor unit number estimates (MUNE) was determined in 10 normal subjects and 10 with amyotrophic lateral sclerosis (ALS). We recorded 500 sequential compound muscle action potentials (CMAPs) at three different stable stimulus intensities (10-50% of maximal CMAP). Estimated mean SMUP sizes were calculated using Poisson statistical assumptions from the variance of 500 sequential CMAP obtained at each stimulus intensity. The results with the 500 data points were compared with smaller subsets from the same data set. The results using a range of 50-80% of the 500 data points were compared with the full 500. The effect of restricting analysis to data between 5-20% of the CMAP and to standard deviation limits was also assessed. No differences in mean SMUP size were found with stimulus intensity or use of different ranges of data. Consistency was improved with a greater sample number. Data within 5% of CMAP size gave both increased consistency and reduced mean SMUP size in many subjects, but excluded valid responses present at that stimulus intensity. These changes were more prominent in ALS patients in whom the presence of isolated SMUP responses was a striking difference from normal subjects. Noise, spurious data, and large SMUP limited the Poisson assumptions. When these factors are considered, consistent statistical MUNE can be calculated from a continuous sequence of data points. A 2 to 2.5 SD or 10% window are reasonable methods of limiting data for analysis.     

Comparison of multiple point and statistical motor unit number estimation

This study compares two common techniques for motor unit number estimation, multiple point stimulation and statistical method, to determine which is more reproducible. Surface recorded motor unit action potentials (SMUPs) of the left hypothenar muscle group were measured on 20 controls and 10 ALS patients. For multiple point, 10 different threshold SMUPs were recorded. For statistical method, mean SMUP amplitude was measured at several stimulus levels, typically spanning >40% of CMAP amplitude range. Both techniques were performed twice, results averaged, electrodes changed, and all recording repeated. For controls, mean of two motor unit number estimation (MUNE) (+/- standard deviation) was 60 (+/-5) for statistical method, and 108 (+/-38) for multiple point. For ALS patients, these values were 21 (+/-16) for statistical method and 55 (+/-39) for multiple point. Test-retest correlation coefficients and coefficients of variation for mean of two MUNE were 0.98 and 7% for statistical method, and 0.90 and 12% for multiple point, respectively. Statistical method was more reproducible and faster than multiple point, supporting its utility in monitoring rates of MUNE change.     

Effect of recording window and stimulation variables on the statistical technique of motor unit number estimation.

A variety of methods are used for the selection of recording window sizes and stimulation current levels for statistical motor unit number estimation (MUNE). This study compares different recording window sizes and stimulation current levels within those windows in the same subjects to determine the effect on MUNE value and reproducibility. Four recording windows of 10% size were compared with four of 5%, with the stimulation current set in the lower quarter, middle half, and upper quarter of the recording window. MUNE for stimulation current set in the lower quarter of the window was 81 (62-103) for 10% recording windows and 120 (108-135) for 5% recording windows, and 91 (61-123) and 133 (120-154) for stimulation current set in the middle half. Increasing the recording window size from 5 to 10% lowers the MUNE value in controls, but tends to improve reproducibility; and setting the stimulation current in the lower quarter of the window, changes the MUNE value minimally, while tending to improve further reproducibility. Excellent reproducibility of MUNE was obtained when applied to a pilot group of 10 amyotrophic lateral sclerosis patients. Based on this study, we conclude that the ideal method for statistical motor unit estimation involves using 10% recording windows and setting the stimulation current in the lower quarter of the recording window.     

Number and relative size of thenar motor units in ALS patients: application of the adapted multiple point stimulation method

In the present study, the adapted multiple point stimulation (AMPS) method was first applied to median innervated thenar muscles in 22 amyotrophic lateral sclerosis (ALS) patients who did not received any treatment. In all patients, a motor unit number estimate (MUNE) and an average surface-recorded motor unit action potential (S-MUAP) size have been derived even if the denervation was severe; and the results were reproducible. The thenar MUNE was less than the normal lower limit for age in 17 patients, and the mean MUNE (67.1 +/- 90.6) was significantly different from that estimated in control subjects (263.3 +/- 116.8). The mean S-MUAP size in the 22 ALS patients was 352.9 +/- 328.4 microV x ms versus 94.1 +/- 30.3 microV x ms in healthy volunteers. A control AMPS was achieved in 8 patients after 2 and 6 months of a glutamate-release antagonist (riluzole) treatment. The mean loss of motor units, based on control thenar MUNEs realized after 6 months of treatment, was 53%. In conclusion, we propose AMPS as a manageable, reproducible and non-invasive procedure which permits one to quantify peripheral denervation and to appreciate the effectiveness of collateral reinnervation in ALS patients.     

Statistical motor unit number estimation: reproducibility and sources of error in patients with amyotrophic lateral sclerosis

The reliability of motor unit number estimation (MUNE) for assessment of the long-term course of ALS is dependent on the reproducibility of the technique. We report our results with the statistical method of MUNE on the ulnar nerve/hypothenar muscle in 16 ALS patients who were studied on 52 occasions. On each occasion, MUNE was performed twice with one electrode placement and once with a different placement. For each MUNE, mean surface motor unit potential amplitude was determined within three different recording ranges or windows at different stimulus intensities. The MUNE results had excellent reproducibility with coefficients of variation of 19% and test-retest correlation coefficients from 0.75 to 0.86. With examination of sources for variability, the reproducibility of statistical MUNE is not affected by minor variation in stimulation and recording electrode placement but may be improved by modifying methods for recording window selection. The high reproducibility of statistical MUNE supports its reliability for estimating the rate of motor unit loss in ALS.     

Reproducibility of statistical motor unit number estimates in amyotrophic lateral sclerosis: comparisons between size- and number-weighted modifications

Motor unit number estimations (MUNEs) can directly assess motor unit populations in muscle and quantify the degree of physiological or pathological motor unit degeneration. A high degree of reproducibility and reliability is required of any effective quantitative tool. MUNE is being increasingly applied clinically, and statistical MUNE has several advantages over alternative techniques. Nevertheless, the optimal method of applying statistical MUNE with respect to its reproducibility has not been established. We performed statistical MUNE by selecting the most compensated compound muscle action potential (CMAP) area as a test area and modified the results obtained by using the weighted mean surface-recorded motor unit potential (SMUP). MUNE measurements made in patients with amyotrophic lateral sclerosis (ALS) showed better reproducibility after incorporating the size-weighted modification. Therefore, we suggest that the size-weighted MUNE in combination with the selection of testing "neurogenically compensated" CMAP areas is a more reliable method of statistical MUNE analysis in ALS patients.     

Proposed modification to data analysis for statistical motor unit number estimate

Motor unit number estimation (MUNE) is an important electrophysiological technique for quantitative measurement of motor neuron loss. Although commonly used, there is no consensus concerning the optimal procedure for statistical MUNE, particularly regarding several operator-dependent variables. To assess the variables, we analyzed 500 sequential, submaximal compound muscle action potential (CMAP) responses at three or four stimulus intensities in 10 controls and 10 patients with amyotrophic lateral sclerosis (ALS). In both controls and ALS patients, we found that posttest filtering data based on 20% or 25% windows or 2, 2.5, or 3 SD excludes <5% of data. Windows of 10% or 15% excluded <5% of data in controls but not in ALS patients. Excluding data based on +/-2 SD, the coefficient of variation for final MUNE was 12% in controls and 6% in ALS patients. Group sizes of 30 or 50 and sample sizes of 300 to 500 sequential CMAP responses per run yielded the lowest coefficient of variation. We propose that statistical MUNE data should be analyzed based on excluding data >2 SD from the mean, because this is operator independent, includes the majority of data, effectively excludes clearly outlying data, such as fasciculations or movement artifact, and has a reasonable coefficient of variation.     

Nerve conduction velocities of single thenar motor axons based on the automated analysis of F waves in amyotrophic lateral sclerosis

The motor unit number estimate (MUNE), motor unit size, and conduction velocity (CV) of thenar surface-recorded motor unit action potentials (S-MUAPs) as collected by the automated F-wave technique were analyzed in 13 patients with amyotrophic lateral sclerosis (ALS) (aged 29–78 years, mean: 61) and 10 age-matched normal subjects (aged 49–81 years, mean: 64). Totals of 96 and 100 thenar S-MUAPs were collected from ALS patients and normal subjects, respectively. There were significant differences (P < 0.001) in the mean estimated numbers and sizes of motor units between the ALS patients (MUNE: 41.9, S-MUAP size: 699.6 μV/ms) and normal subjects (MUNE: 151.2, S-MUAP size: 244.1 μV/ms). The mean S-MUAP CV was 46.3 m/s (range: 32–59) for ALS patients and 56.5 m/s (range: 43–69) for normal subjects (P < 0.001). Mean median motor nerve CVs, measured in the forearm segment, were not significantly different (P = 0.79) between ALS patients (53.4 m/s) and normal subjects (52.9 m/s), however. Thenar motor unit CVs are significantly reduced in ALS patients as compared to normal controls, and this may be due to proximal motor nerve slowing. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21:756–761, 1998.     

Thenar motor unit number estimates using the multiple point stimulation technique: Reproducibility studies in als patients and normal subjects

Thenar motor unit number estimate (MUNE) reproducibility was assessed in 20 patients with amyotrophic lateral sclerosis (ALS) and 16 normal subjects using the multiple point stimulation (MPS) technique. The MUNE was calculated by dividing the thenar compound muscle action potential negative-peak (n-p) area by the mean n-p area of 10 lowest threshold, all-or-nothing, surface-recorded motor unit action potentials. Two trials (test–retest) were performed by the same examiner either on separate days or on the same day with new electrode placements. The mean test MUNE was 43.4 (SD: 35.9, range: 6–145) for ALS patients and 219.4 (SD: 80.8, range: 122–368) for normal subjects. Test–retest MUNE differences were not significant for ALS patients or normal subjects. The test–retest correlation coefficient (r) was 0.99 for ALS patients and 0.85 for normal subjects. The mean difference between test–retest values was 10% for ALS patients and 17% for normal subjects. Test–retest reproducibility of the thenar MUNE using the MPS technique is high in both ALS patients and normal subjects. The reliability of the MPS technique in estimating motor unit numbers may make it a useful outcome measure in following the course of patients with progressive lower motor neuron disease, especially those enrolled in experimental drug trials.© 1995 John Wiley &Sons, Inc.     

Origin of surface motor unit potentials in hypothenar motor unit number estimation

Introduction: Far‐field potentials (FFPs) from muscles other than the abductor digiti minimi (ADM) may interfere with motor unit number estimation (MUNE) from that muscle. Methods: We identified the origin of each surface motor unit potential (SMUP) during hypothenar MUNE using the multiple point stimulation method in 20 control subjects by recording from individual ulnar‐innervated muscles with a common proximal reference (pref). Results: ADM SMUPs comprised 39.0% of the accepted SMUPs, followed by those from the fourth dorsal interosseous muscle (14.0%), the fourth lumbrical muscle (9.2%), and the second and third palmar interosseous muscles (8.8% each). The percentage of ADM SMUPs varied from 18% to 73% of accepted SMUPs among individual subjects. Accepted non‐ADM SMUPs were usually much smaller than ADM SMUPs, and many more non‐ADM SMUPs were excluded due to their small size. Conclusions: A large contribution from non‐ADM or non‐hypothenar SMUPs obscures the meaning of the MUNE value. Muscle Nerve, 48: 185–190, 2013     

Bayesian statistical MUNE method

We have developed a new method of motor unit number estimation (MUNE) for assessing diseases such as amyotrophic lateral sclerosis (ALS). We used data from the whole stimulus-response curve and then performed a Bayesian statistical analysis. The Bayesian method uses mathematical equations that express the basic elements of motor unit activation after electrical stimulation and allows for the sources of variability and uncertainty in this formulation. The Bayesian MUNE method was used to determine the most probable number of motor units in 8 normal subjects, 49 ALS subjects, and 3 subjects with progressive lower motor neuron (LMN) weakness. In normals the number of motor units was calculated to be 75-85 in hand and 40-58 in foot muscles. In ALS subjects the number of motor units per muscle was less than in normal subjects. In 17 ALS subjects and 3 subjects with LMN weakness the median, ulnar, or peroneal nerve was studied on repeated occasions over an average of 189 days (range 63-1,071) and the number of motor units progressively declined, with a half-life ranging from 62-834 days. The results of our MUNE technique were reproducible on replicate studies. A Bayesian statistical MUNE method is a new approach that can be used to study ALS patients serially for assessment and treatment trials.     

Proximal-distal motor unit number estimation-dynamic changes in patients with amyotrophic lateral sclerosis A one-year follow-up

BACKGROUND:Amyotrophic lateral sclerosis (ALS) is the most common of all the motor neuron diseases and the absence of a biologic marker has made both diagnosis and tracking evolution of the disease difficult, Electrodiagnostic tests play a fundamental role in quantifying pathological changes in the motor unit pool.OBJECTIVE:We assessed distal-proximal Motor Unit (MU) loss and changes using the method of motor unit number estimation (MUNE).DESIGN, TIME AND SETTING:A case-control study was performed at the Department of Neuroscience, Pisa University Medical School, Italy from December 1999 to November 2009. PARTICIPANTS:A total of 50 ALS patients were recruited, 30 males:mean age (59.6 ± 13.3) years; 20 females:mean age (63.9 ± 11.7) years; range (30-82) years; all patients had probable or definite ALS. Thirty healthy volunteers were recruited from department staffs, including 20 males and 10 females; mean age (57.7 ± 13.8) years served as controls.METHODS:MUNE was performed for both the biceps brachii and abductor digiti minimi muscles of the same side. The technique used relayed substantially on manual incremental stimulation of the motor nerve, known as the McComas technique (50 ms sweep duration, a gain of 2 mV/Div for M wave, 0.5 mV/Div for each step; filters 10-20 kHz).MAIN OUTCOME MEASURES:MUNE results were measured.RESULTS:Functioning MU numbers, measured by MUNE, decreased in the biceps brachii and abductor digiti minimi muscles over the entire one-year follow-up period (one assessment every three months) compared with baseline determination, the rate of MU decrease was similar in both muscles, but steeper distally.CONCLUSION:MUNE is a feasible method for ALS patients both proximally and distally to track changes over time in muscle MUs during the disease's evolution.     

Trans-synaptic degeneration of motoneurons distal to chronic cervical spinal cord compression in cervical spondylotic myelopathy

Objective: To assess the effect of chronic cervical spinal cord compression upon remote motor unit function in patients with cervical spondylotic myelopathy (CSM). Methods: Fifty-three CSM patients and 47 healthy subjects were included. Bilateral motor unit number estimations (MUNEs) were recorded from both abductor digiti minimi and abductor pollicis brevis, and bilateral flexor carpi radialis (FCR) H-reflexes were examined in all subjects along with the nine-hole peg test (NHPT). The main outcome measures included the number of motor units, the average single motor unit potential (SMUP) area, the FCR Hmax/Mmax ratios and the NHPT time. Results: Statistically significant results compared to healthy controls included increased average SMUP area, increased FCR Hmax/Mmax ratio and increased NHPT time (p < 0.05). Abnormal SMUP was observed in 10/53 (18.9%) CSM patients along with reduced motor units in 3 of these 10 patients, while the FCR Hmax/Mmax ratios in the CSM patients with abnormal MUNE were higher than those in others (p < 0.05). There was a positive correlation between the NHPT time and the average SMUP area, and a negative correlation was noted between the NHPT time and the number of motor units (p < 0.05). Conclusion: In CSM patients, the motor units below the level of compression may exhibit dysfunction, which is likely a result of trans-synaptic degeneration. Both cervical spinal cord compressive injury and this trans-synaptic degeneration contribute to the impairment of fine motor ability in CSM patients. Therefore, treatment and rehabilitation efforts should account for these two dysfunctions.     

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.     

Number of Edb motor units estimated using an adapted multiple point stimulation method: normal values and longitudinal studies in ALS and peripheral neuropathies.

OBJECTIVE: To validate the adapted multiple point stimulation (AMPS) method to estimate the number of motor units (MUNE) from the extensor digitorum brevis (Edb) muscle. METHODS: Twenty controls (10 young and 10 old) were examined on both sides and 10 patients with amyotrophic lateral sclerosis (ALS) and 5 with acute peripheral neuropathy (PN) were examined longitudinally on one side during a series of repeated electrophysiological sessions. RESULTS: In the controls, the median MUNE and size of the motor unit action potentials (S-MUAPs) were found to be age-related (411 and 70 microVms in the young group; 164 and 142 microVms in the old group; P < 0.01), with a coefficient of variation of MUNE values of 27% and 20%, respectively. In the ALS group, the median MUNE value at diagnosis was 31 (P < 0.05 vs. controls), and during a mean follow-up period of 11.5 months a continuous decrease in the MUNE value was seen, together with an initial increase, followed by a later decrease in 4 cases, in S-MUAP size. In the PN group, the MUNE value was initially similar to that in controls, but then decreased, accompanied by an increase in S-MUAP size, and then showed a progressive increase, together with a decrease in S-MUAP size. CONCLUSIONS: AMPS, a MUNE method developed in the upper extremity, also appears to be a useful procedure for quantifying changes in the MUNE value in the Edb muscle without specific software in order to study age-related changes or changes in patients with ALS or PN.     

Detection of preclinical motor neurone loss in SOD1 mutation carriers using motor unit number estimation

OBJECTIVE: To determine the pattern of motor neurone loss in amyotrophic lateral sclerosis (ALS). In particular, to determine whether there is a gradual life long presymptomatic motor neurone loss or, alternatively, a sudden catastrophic loss just before the onset of symptoms. METHOD: The statistical motor unit number estimation (MUNE) technique was used in a longitudinal study of 19 asymptomatic carriers of the Cu, Zn superoxide dismutase 1 (SOD1) gene. MUNE results were compared with those of 34 age and sex matched SOD1 negative family controls and 23 population controls. Motor neurone loss was also estimated in 12 patients with sporadic ALS. 84 subjects (43 male and 41 female patients) with an age range from 16-73 years were followed up over three years, both clinically and by MUNE, every six months. RESULTS: In 2 of the 19 mutation carriers, there was a sudden reduction in MUNE several months before the onset of weakness. The patients with symptomatic sporadic ALS also had a reduced MUNE, but there was no detectable loss of motor neurones in the remainder of the subjects. CONCLUSION: MUNE can be used to detect preclinical loss of motor units in familial ALS. Normal numbers of motor neurones were maintained in 17 SOD1 mutation carriers over the three year period. There was an abrupt loss of motor neurones just before the onset of symptomatic weakness in two SOD1 mutation carriers. These results suggest that some form of trigger may initiate rapid cell loss and death of motor neurones just before the onset of symptoms.     

Effect of small motor unit potentials on the motor unit number estimate

Small surface motor unit potentials (S-MUPs) may have a negative influence on the variability of the motor unit number estimate (MUNE). According to published consensus criteria S-MUPs with a negative peak amplitude smaller than 10 muV should be omitted. The effect of omitting small S-MUPs on the MUNE was evaluated using a simulation model. The model incorporated a healthy and amyotrophic lateral sclerosis (ALS) distribution formed with real S-MUPs. Using a random drawing process the MUNE was calculated with and without small S-MUPs. In the healthy population 27% of all S-MUPs were small. MUNE determined without these S-MUPs was marginally less variable. However, MUNE values dropped about 24% at a sample size of 20. In ALS, only 12% of the total population of 130 S-MUPs were small. MUNE dropped about 12% without the small S-MUPs. By omitting small S-MUPs the differences between the healthy and ALS distributions become smaller. Therefore, incorporating small S-MUPs in the estimate is suggested.     

A motor unit number estimate (MUNE)--a quantitative and pathophysiologic parameter for amyotrophic lateral sclerosis (ALS)]

We performed rate studies to develop a new method to obtain a MUNE reflecting the number of spinal alpha-motor neurons (MN). In the physiological part, six unitary muscle action potential (uMAPs) of the medial gastrocnemius muscle (MG) were averaged to obtain the mean uMAP, and a MUNE was calculated by dividing the area of its compound muscle action potential (CMAP) by the area of the mean uMAP. In the anatomical part, cholera toxin was injected into the MG muscle, and we counted the number of MG MNs identified by immunohistochemical staining of the toxin in their somata. We found that a MUNE of the MG muscle was consistent with the number of MG MNs. In the clinical application, we obtained MUNEs in 10 patients with ALS and 20 control subjects. In each patient we recorded 10 uMAPs and CMAP at each of the hypothenar and extensor digitorum brevis muscles using fine needle electrodes placed in these nerves. MUNEs for these muscles were calculated in the same way as described above. In the ALS patient group at one year post-onset of symptoms, the MUNEs for these two muscles were decreased to about 30% of the norm. We concluded that progression of ALS could be quantified by MUNEs.     

Motor unit number estimation predicts disease onset and survival in a transgenic mouse model of amyotrophic lateral sclerosis

Motor unit number estimation (MUNE) has proved useful in predicting rate of progression and survival in patients with amyotrophic lateral sclerosis (ALS). In animal models, it has demonstrated physiological effects of experimental medications that were not evident behaviorally. We sought to determine more specifically what aspects of function and survival that MUNE could predict in the G93A transgenic mouse model of ALS. Transgenic mice were examined in two distinct treatment studies, neither of which showed an effect of drug on survival, behavioral measures, or MUNE. MUNE was performed using a modification of the incremental stimulation method by stimulating the sciatic nerve at the sciatic notch, and recording with a circumferential surface electrode around the ipsilateral distal hindlimb. Both limbs were studied and the results averaged. MUNE was performed longitudinally on all animals from near onset to premorbid state. Each study was evaluated separately. For both studies, MUNE at initial study correlated significantly with behavioral determination of disease onset, and MUNE slope from initial to final study correlated significantly with disease duration, as measured from onset to time of death. However, the final MUNE value did not correlate with survival. Thus, in two studies involving animals with quite different disease courses, initial MUNE effectively predicted symptom onset and MUNE slope predicted survival. This suggests that MUNE has potential efficacy as a useful functional outcome measure in both animal and human studies of ALS.     

Use of Bayesian MUNE to show differing rate of loss of motor units in subgroups of ALS

Objectives

To evaluate differences among patients with different clinical features of ALS, we used our Bayesian method of motor unit number estimation (MUNE).

Methods

We performed serial MUNE studies on 42 subjects who fulfilled the diagnostic criteria for ALS during the course of their illness. Subjects were classified into three subgroups according to whether they had typical ALS (with upper and lower motor neurone signs) or had predominantly upper motor neurone weakness with only minor LMN signs, or predominantly lower motor neurone weakness with only minor UMN signs. In all subjects we calculated the half life of MUs, defined as the expected time for the number of MUs to halve, in one or more of the abductor digiti minimi (ADM), abductor pollicis brevis (APB) and extensor digitorum brevis (EDB) muscles.

Results

The mean half life of MUs was less in subjects who had typical ALS with both upper and lower motor neurone signs than in those with predominantly upper motor neurone weakness or predominantly lower motor neurone weakness. In 18 subjects we analysed the estimated size of the MUs and demonstrated the appearance of large MUs in subjects with upper or lower motor neurone predominant weakness. We found that the appearance of large MUs was correlated with the half life of MUs.

Conclusions

Patients with different clinical features of ALS have different rates of loss and different sizes of MUs.

Significance

These findings could indicate differences in disease pathogenesis.