Number and relative size of thenar motor units estimated by an adapted multiple point stimulation method

An adapted multiple point stimulation (AMPS) method is described for estimating the number and relative size of thenar motor units. With this method, the median nerve was stimulated at various sites from the wrist to the elbow. To avoid alternation, only two or three clearly identifiable surface-recorded motor unit action potentials (S-MUAPs) were recruited at each point by incremental stimulation. A total of 10 S-MUAPs, eleicited from four to five distinct stimulatin points, was used to calculate the average S-MUAP size. By dividing the maximum M-potential size by that value, a motor unit number estimate (MUNE) was derived. In 59 healthy volunteers, from 19 to 87 years old, the mean average S-MUAP size was 87 ± 27.6 μV. ms and the mean MUNE was 278 ± 113 motor units. When performed repeatedly, the results were reproducible. The number of motor units declined exponenetially with age while average S-MUAP sized increased only moderately. To assess the validity of the AMPS method, its results were correlated with those obtained using the F-response technique. The correlation coefficient was 0.83 (P < 0.001). © 1995 John Wiley & Sons, Inc.     

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.     

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.     

The estimated numbers and relative sizes of thenar motor units as selected by multiple point stimulation in young and older adults

Multiple point stimulation (MPS) is described as a method of estimating the numbers of motor units in the median innervated thenar muscles of young and older control subjects. Stimulation at multiple sites along the course of the median nerve was employed to collect a sample of the lowest threshold, all-or-nothing surface-recorded motor unit action potentials (S-MUAPs). The average, negative peak area, and peak-to-peak amplitude of the sample of S-MUAPs was determined and divided into the corresponding value for the maximal compound muscle action potential to derive the motor unit estimate (MUE). In 37 trials from 17 younger subjects (20—40 years), the mean MUE was 288 ± 95 SD based on negative peak area and, in 33 trials from 20 older subjects, mean values were 139 ± 68. In 23 young and older subjects, MPS was performed on at least two occasions and the MUEs were found to be highly correlated (r = 0.88). © 1993 John Wiley & Sons, Inc.     

Functional properties of motor units in motor neuron diseases and neuropathies

The relationship between the size of single motor unit (MU) action potentials and their twitch properties was estimated in patients with spinal muscular atrophy (SMA, n=5) and amyotrophic lateral sclerosis (ALS, n=10), as well as in patients with peripheral nerve lesions (PNL, n=9). The data obtained from these groups were compared to normal controls (n=8). In controls, the single MU twitch force was highly correlated to the corresponding EMG potential size in terms of macro EMG area. An enlargement of MUs, due to collateral sprouting and reflected by increased potential size and twitch force, was found in regenerating PNL and in slowly progressing SMA. Both parameters were highly correlated which indicates a high functional quality of compensating mechanisms. However, in rapidly progressing forms of amyotrophic lateral sclerosis (ALS) this correlation is poor and reflects a disturbance of the contractile system. Contraction times and half relaxation times were not correlated in the different groups.     

Pattern of recruiting human motor units in neuropathies and motor neurone disease

The pattern of recruiting human motor units in the first dorsal interosseous muscle of the hand has been studied in 31 patients with ulnar neuropathies and motor neurone disease. Two years after surgical repair of an unilateral complete severance of the ulnar nerve, the twitch tensions increased to normal size. However, the normal orderly pattern of recruiting motor units of increasing size during increasing voluntary contractions was irretrievably lost. Among patients with pressure or entrapment neuropathies, the normal orderly pattern of recruiting motor units was always retained. Similarly, in patients with motor neurone disease (amyotrophic lateral sclerosis), the orderly pattern of recruitment was not disrupted.     

Assessment of central motor conduction to intrinsic hand muscles using the triple stimulation technique: normal values and repeatability.

OBJECTIVE: To establish the triple stimulation technique (TST) for recordings from the first dorsal interosseus (FDI) and the abductor pollicis brevis muscles (APB), and to analyse the test-retest repeatability of the TST measurements in APB. METHODS: The recently developed TST was slightly modified for recordings from small hand muscles to account for volume conducted activity from surrounding muscles. The TST combines transcranial magnetic stimulation (TMS) with a peripheral collision technique [Magistris et al. Brain 121 (1998) 437]. In contrast to conventional motor-evoked potentials (MEPs), it quantifies the number of conducting central motor neurons (expressed by the TST amplitude ratio, TST-AR). MEPs and TST were performed in 30 sides of 25 healthy subjects (target muscle FDI), and in 29 sides of 21 healthy subjects (target muscle APB). All APB recordings were repeated after 25+/-5.9 days. RESULTS: The TST-AR averaged 97.4+/-2.5% in FDI and 95.9+/-4.7% in APB. There was a mean difference of the TST-AR ratio of 2.9+/-3.1% between the repeated APB recordings (95% limits of agreement+/-6.3%). CONCLUSIONS: TMS allows activation of virtually all motor neurons supplying FDI and APB, when effects of volume conduction are eliminated. Its test-retest repeatability is excellent. SIGNIFICANCE: The TST is well suited for follow-up examinations of central motor conduction failures. The greater number of established target muscles widens its clinical applicability.     

Magnetic brain stimulation: central motor conduction studies in multiple sclerosis

Central motor conduction (CMC) was evaluated in 32 normal subjects and 83 patients with multiple sclerosis, and the findings were correlated with clinical signs and evoked potential data. CMC time was obtained from the latency difference in responses from the abductor muscle of the little finger to magnetic stimulation of the motor cortex and electrical stimulation at the C-7/T-1 interspace. Mean CMC time in normal subjects was 6.2 msec (SD 0.86 msec), and amplitudes of responses to cortical stimuli were at least 18% of those obtained with stimuli at the wrist. CMC was abnormal in 60 patients with multiple sclerosis (72%); this correlated well with brisk finger flexor jerks (p less than 0.005). CMC was abnormal in 79% of patients with weakness of the abductor muscle of the little finger and in 54% with a normal muscle. Neurological examination was normal in 7 arms with abnormal CMC. Visual evoked potentials were abnormal in 67%, somatosensory evoked potentials in 59%, and brainstem auditory evoked potentials in 39% of those tested. For each procedure more subjects had abnormal CMC and normal evoked potentials than the reverse. The technique is of value for demonstrating and documenting central motor pathway lesions in multiple sclerosis, especially when physical signs are equivocal.     

Contractile and electrical properties of human motor units in neuropathies and motor neurone disease

The contractile and electrical properties of motor units in the first dorsal interosseous muscle of the hand have been studied in 26 patients with ulnar neuropathies and motor neurone disease (amyotrophic lateral sclerosis). Among patients with unilateral pressure or entrapment ulnar neuropathies, there was a tendency for the twitch tensions for single motor units to be smaller, while the surface EMG amplitudes were generally larger in the affected hands. Very large EMG amplitudes but normal size twitch tensions were observed among the motor neurone disease patients, indicating that, in general, motor units enlarged by sprouting are less efficient contractile units than units of normal physiological size.     

The numbers and relative sizes of motor units estimated by computer.

A fully automated system is described for estimating the numbers and relative sizes of functioning motor units in proximal and distal muscles of the arm and leg. In this system, a computer controls the motor nerve stimulation, and analyzes the potentials evoked from the muscles; a subprogram searches for instances of "alternation." In 33 healthy volunteers, aged 21 to 56 years, the median-innervated thenar muscles of one hand were tested 2 to 3 times; the mean motor unit estimate was 228 +/- 93 SD. For similar numbers of biceps brachii, extensor digitorum brevis, and vastus medialis muscles, the respective mean values were 113 +/- 40, 131 +/- 45, and 229 +/- 108 units. The reproducibility of the method was such that the overall coefficient of variation, for the normalized results from the 121 muscles studied, was 22%. The reliability of the automated method was doubled if 3 estimates, rather than one, were performed on each muscle. Comparisons of the results obtained by automated and "manual" methods indicated that the computer-derived values tended to be lower by approximately 33%.     

Cervical nerve root stimulation. Part II: findings in primary demyelinating neuropathies and motor neuron disease.

OBJECTIVE: Cervical nerve root stimulation (CRS) allows the assessment of conduction in the proximal segments of motor fibers destined to the upper extremities, which are not evaluated by routine nerve conduction studies (NCS). Since many primary demyelinating polyneuropathies (PDP) are multifocal lesions may be confined to the proximal nerve segments. CRS may therefore increase the yield of neurophysiologic studies in diagnosing PDP. METHODS: We reviewed clinical and neurophysiologic data from 38 PDP patients and compared them to 35 patients with motor neuron disease (MND), and 21 healthy controls (HC). RESULTS: Mean onset-latency was significantly prolonged in PDP patients. The optimal onset-latency cutoff necessary to distinguish PDP from MND and controls was 17.5 ms for the abductor pollicis brevis (APB) and abductor digiti minimi (ADM), and 7 ms for Biceps and Triceps. Mean reduction in proximal to distal CMAP amplitude to APB and ADM was significantly greater in PDP patients, with an optimal cutoff in proximal to distal CMAP amplitude reduction necessary to distinguish PDP from MND and HC being 45%. CONCLUSIONS: CRS is effective in distinguishing PDP from MND and HC based on prolonged onset latency and conduction block criteria. SIGNIFICANCE: CRS may increase the diagnostic yield in cases where demyelinating lesions are confined to the proximal peripheral neuraxis.     

Axonal refractory period of single short toe extensor motor units in neuropathies and neuromuscular diseases.

Electromyographic recordings were carried out on 36 patients with neuropathies and neuromuscular disorders with a selectivity permitting identification of single motor unit potentials during maximal voluntary effort and after supramaximal nerve stimulation. The axonal conduction velocity and refractory period of 117 motor units were determined and the findings were compared to those in previously studied normal subjects. The axonal conduction velocity spectrum was 15-52 m/s. Fifteen per cent of all motor units had axonal conduction velocities below 30 m/s which is below the normal range. When test stimulus strength was 10% above the axonal threshold at rest the refractory period was 1.88 +/- 0.43 ms which is slightly longer than the corresponding value in healthy subjects (1.67 +/- 0.25 ms). The relationship between the axonal conduction velocity and refractory period observed in healthy subjects did not hold for these patients. Thirty-eight per cent of all motor motor units with axonal conduction velocities within the normal range had refractory periods longer than 2.0 ms which was only infrequently observed in healthy subjects. When test stimulus strength was 50% above the axonal threshold at rest the refractory period was 1.16 +/- 0.42 ms which was significantly longer (p less than 0.02) than in healthy subjects (0.64 +/- 0.21 ms). At this stimulus strength 40% of all motor units with axonal conduction velocities within the normal range had refractory periods above 1.0 ms which was never the case in healthy subjects. The significance of these findings with regard to the clinical application of the Hopf technique for determining the conduction velocity spectrum of peripheral motor nerves is discussed.     

Effect of neurophilin ligands on motor units in mice with SOD1 ALS mutations.

BACKGROUND: Mice with trangenes that express mutations in the gene for cytosolic copper/zinc superoxide dismutase (SOD1) develop motor neuron degeneration resembling human ALS. Neurophilin ligands are small molecules that promote neurite outgrowth. OBJECTIVE: To test the hypothesis that treatment with two neurophilin ligands increases survival in these ALS mice by slowing the loss of motor neurons and increasing the sizes of motor units. METHODS: Transgenic mice hemizygous for the G93A mutation were untreated or treated from 30 days of age with one of two doses of two neurophilin ligands (V-13,670; V-10,367, Vertex Pharmaceuticals, Boston, MA). Onset of behavioral abnormalities and survival were recorded. Motor unit number estimation (MUNE) was performed every 21 days starting at age 60 days. RESULTS: In control animals, disease onset occurred at 77.0 days of age and death occurred at 137 days of age. Neither neurophilin ligand affected the disease course. In control animals, MUNE declined with time beginning before behavioral abnormalities were noted, and motor unit size increased concomitantly. There was no effect of drug on motor unit loss as assessed by MUNE; however, motor unit size increased more rapidly and to a greater degree in animals treated with V-13,670. CONCLUSION: As in human ALS, the transgenic ALS mice show physiologic changes in the motor unit prior to the development of clinical signs: MUNE declines as motor unit size increases. Although neither neurophilin ligand significantly affected survival, one produced an increase in motor unit size. The fact that survival was not altered by the increase in motor unit size may reflect the rapid disease course in this animal model.     

Diaphragm motor responses to phrenic nerve stimulation in ALS: Surface and needle recordings

Objective

In studies of phrenic nerve (PN) conduction in amyotrophic lateral sclerosis (ALS) both motor response amplitude and latency have been reported as abnormal. However, correlation with diaphragm motor unit loss, and with diaphragmatic function has not been fully evaluated.

Study of central motor pathways using cortical magnetic stimulation and spinal electrical stimulation: results in 20 normal subjects

Evoked motor potentials can be elicited by magnetic cortical or electric spinal stimulations. The central conduction time (CCT) corresponds to the difference in latencies between the total conduction time (from cortex to muscle) and the peripheral conduction time (from spinal cord to muscle). CCT is the sum of the conduction time in the cortico-spinal fibers, of the spinal synaptic delay, and of the conduction time in the proximal part of the motor roots. CCT values (mean + standard deviation) were determined in 20 healthy subjects ranging from 21 to 56 years of age (mean 31.2). Results of magnetic cortical stimulation were compared to the results of electrical stimulation of the cortex. CCTs after magnetic cortical stimulation were longer than CCTs after electric cortical stimulation. This could be explained by the fact that electrical stimulation elicits a direct response in the cortico-spinal tract whereas magnetic cortical stimulation has indirect effects on the pyramidal cells of the motor cortex through excitatory interneurons. Compared with electrical stimulation, the magnetic stimulation has the great advantage of being painless and allows a safe evaluation of the central motor pathways in man.     

Extraocular motor units: type classification and motoneuron stimulation frequency-muscle unit force relationships.

Extracellular and intracellular techniques were used to study single motor units of the abducens nucleus and lateral rectus muscle in the cat. Using a combination of two motor unit properties, the fusion frequency and an index of fatigability, the population of twitch motor units could be separated into 4 subgroups: fast fatigable (FF), fast fatigue resistant (FR), slow fatigable (SF) and slow fatigue resistant (S). Nontwitch motor units, a fifth subgroup (NT), formed 10% of the total studied population. The twitch tension and the maximum tetanic tension of the FF motor unit type were significantly stronger than all other motor unit types. The use of frequency varying stimulation patterns did not further differentiate the motor unit types. The relation between a series of single motoneuron stimulation frequencies and the resultant single muscle unit forces generated a slope defined as a motor unit's kt value. Motor units with low kt values had higher twitch tensions, higher maximum tetanic tensions, higher fusion frequencies and lower fatigue indices than motor units with high kt values. Motoneuron recruitment was tested by electrical stimulation of the medial rectus subdivision of the contralateral oculomotor nucleus. No correlations were seen between recruitment order and the mechanical parameters of the single abducens motor units.     

Transdermal absorption of estradiol in normal subjects and in patients with peripheral neuropathies

Abstract. The relationship of disturbed autonomic skin innervation to altered transdermal absorption in polyneuropathy is not yet clear. In this study we measured serum estradiol in 29 normals and 10 polyneuropathy patients to assess potential differences of estradiol uptake from different skin sites.     

Sympathetic skin response--a method of assessing unmyelinated axon dysfunction in peripheral neuropathies.

The sympathetic skin response (SSR) was measured in 33 patients with peripheral neuropathies and in 30 normal control subjects. Abnormalities of the response were correlated with clinical, pathologic, and EMG observations. The response was usually absent in axonal neuropathies, but present in demyelinating disorders. Abnormalities of the sympathetic skin response did not correlate well with clinical evidence of dysautonomia, but were a reliable indicator of disorders affecting unmyelinated axons.