Clinical electromyographic studies of diseases of the motor unit

Electroencephalography and Clini~_alNeurophys.iolo~'. 1974. 36: 395-401 ~" Elsevier Scientific Publishing Company. Amsterdam - Printed in The Netherlands

CLINICAL

ELECTROMYOGRAPHIC

OF THE MOTOR

STUDIES

395

OF DISEASES

UNIT

J. H. PHAJAN Departmen! of Neurology. IJnh'ersit.r rJl-Utah Colh.qe of Medicim.. Sub Lake City. Utah 84112 t L'r.S.A. ) (Accepted tier publication: October 22. 1973}

The electromyographer examines single motor unit action potentials firing at minimal and moderate effort, The frequency, amplitude, duration and shape of these potentials provide valuable information with respect to pathological alterations of the motor unit. it has been pointed out that motor unit action potential duration varies from one muscle to another (Buchthal et aL 1957), Frequency at onset of firing also varies from one muscle to another: frequency at recruitment of a second unit is less variable lPetajan and Philip 1969). it has been shown that within a given muscle the motor units can be classified into tonic and phasic types depending upon the variance of firing rate as a function of frequency (Tokizane and Shimazu 1964). Histochemically most muscles in man have been shown to consist of at least two types of motor units, likely corresponding to the older slow and fast or red and white classifications (Romanul 1964). When contraction is initiated and effort is gradually increased, small tonic motor units are the first to become activated (Grimby and Hannerz 1968). Different motor units may be activated depending upon whether or not the contraction approaches isotonic or isometric conditions and depending upon the rate ofcontraction as well (Grimby and Hannerz 1968). The above facts lead to several considerations in relation to clinical electromyography (EMG) and the investigation of motor control. Examinations of single motor units by means of standard EMG procedures evaluate a particular population of motor units; in general, the small, low threshold, relatively tonic, motor units. However, the degree of variability in firing rate as a function

of frequency differs appreciably from one muscle to another, Even the region within a muscle from which a recording is made is important. A disease process may be selective in its involvement of a particular type of motor unit. It is assumed that, within a particular muscle, tonic motor units are more likely to be type I and phasic units type 11. Absolute confirmation of this difference is not available for man. In certain muscle diseases the hope of the histochemist to find selective involvement of certain fiber types has been realized. Engel (1970) uses this fact as a basis for classification of muscle disease into type specific and non-type specific disorders. As yet there is no corresponding EMG classification. As denervation or muscle fiber necrosis results in a loss of motor units, at least two phenomena can be expected to occur. First, the disease process may select a specific motor unit type. If the small motor units that initiate contraction are affected, then the tendency will be for other types of motor units to fulfil this fu,ction. Second, as the number of motor units decreases for whatever reason, it will be possible to discriminate single units participating in contraction at relatively higher levels of effort. In both circumstances the frequency of firing at onset and at recruitment of other units and the variance of interspike interval at any mean interspike interval can be expected to change. Techniques are now available to discriminate single units on the basis of amplitude and shape characteristics. In this study an analysis of motor unit frequency characteristics at onset and recruitment in patients with myopathy, neuropathy and amyotrophic late:ai sclerosis has been undertaken. Comparison with onset and recruitment values from normal subjects has been made.

396

J.H. PETAJAN

METHODS

Single motor unit action potentials initiating muscle contraction were recorded on magnetic tape with audio-visual feedback to establish control. The firing rate at onset and recruitment of a second motor unit was determined. Recorded data were then played back and measured by display on a Tektronix 564 storage oscilloscope. Approximately 10-20 interspike intervals were measured for each unit at onset and recruitment. Means and standard deviations were calculated for units of a given muscle and pathological condition. The diseases represented in each diagnostic category are given in Table I. The diagnosis in each instance was determined by means of EMG, determination of peripheral motor nerve conduction velocity, as well as muscle biopsy. A myopathy was defined as a condition in which histological evidence for loss of muscle fibers by necrosis or hypotrophy was accompanied by a significant decrease in mean total duration and amplitude of motor unit action potentials. Neurogenic atrophy was defined as a condition in which histological and histochemical evidence for single fiber atrophy. fiber type grouping or grouped atrophy was accompanied by a significant increase in mean total duration and amplitude of motor unit action potentials. Determination of the specific type of neurogenic atrophy was by evaluation of TABLE I Diagnostic category

Neuropathy Peroneal neuropathy {compression or trauma at head of fibula) Ulnar neuropathy (compression at elbow) Circumflex nerve compression Brachial plexopathy Lumbo-sacral radiculopathy Amyotrophic Lateral Sclerosis Myopathy Inflammatorymyopathy ....acute or subacute Limb-girdle dystrophy Type I1 hypotrophy Progressive muscular dystrophy (Duchenne) Steroid myopathy

No. of patients

6 4 i 2 3 8 4 3 I ! !

peripheral motor nerve conduction velocity, the distribution of involved muscles, and other clinical findings. Muscles at intermediate stages of involvement were selected for study. Comparison was then made with data from corresponding muscles of normal subjects. However, pooled data from the patient population compared with the pooled normal data will be described here, because they disclose what significant differences there are among the various categories. RESULTS

Some comment on EMG technique is in order. It is accepted that involvement of skeletal muscle by any disease whatever is not uniform. The degree of involvement varies depending upon proximal-distal location and may vary considerably within the muscle itself. It is likely that the electromyographer with his needle electrode may encounter numerous areas in which motor unit action potentials are normal in amplitude, duration, shape and frequency. If such is the case, then he must examine many areas and assess the number of abnormal potentials found in relation to the total examined. Thus, in this study some patients with neuromuscular disease often had action potentials with normal frequency and other characteristics. As a consequence pooled data can only indicate the direction of change. However, criteria for normal firing rate can be applied in the diagnosis of neuromuscular disease, if one determines the relative number of potentials which fall outside the normal range for any characteristic.

Neuropathy Sixteen adult patients with neuropathy were studied. As was the case in all disease categories, the data obtainable from each patient were variable. The data presented are representative of the pathological findings. While single units with normal firing rates at onset and recruitment of a second unit were found (see Fig. I for normal values), a common finding was increased firing rates at onset and recruitment (Table Ill. The distribution of onset and recruitment intervals was skewed toward higher firing rates (Fig. 2). Finding single motor units firing at rates significantly above normal without recruitment was

CLINICAL

EMG

397

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characteristic ofa neuropathic process (P < 0.001 for onset and recruitment means compared with normal values).

Myopathy Eight adults and two adolescents in this cate-

gory were examined. Firing rate at onset and recruitment was incre~tsed {Table I1). However. the distribution of onset and recruitment intervals is now skewed toward lower firing rates with some intervals falling into the norm~,l range {Fig. 3). Since the degree of recruitment in pro-

J.H. PETAJAN

398 TABLE II

ONSET

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Mean interspike interval values and standard deviations in milliseconds are shown for the three conditions studied as well as for normal subjects. NEUROPATHY

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portion to effort was much increased, it was essential to examine firing rate at very minimal effort. In patients with a severe degree of involvement, regions were found in which recruitment did n o t occur. Thus, even in myopathy recruitment can be incomplete when motor units are lost through muscle fiber necrosis, causing firing rate to increase at onset and recruitment. When involvement was mild to moderate, firing rates tended toward normal. It can be noted in Table I I that both acquired and inherited myopathies are considered as one group. Taking the variance of the data from individual cases into consideration

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CLINICAL

399

STUDIES

EMG

it did not seem reasonable to separate the myopathies into two categories. Further, the reduction in total duration and amplitude of single motor unit action potentials in such conditions as steriod myopathy or type I hypotrophy was greater than that seen in patients with inflammatory mjopathy. This was the case despite the fact that the proportion of fibers undergoing necrosis wasfar greater in the latter condition. Thus, the characteristics whica are attributed to myopatl':ic change were l~resent in sufficient degree in each condition to warrent their collection in one group. A question remaining unanswered is the poor correlation between histological evidence for fiber loss as in type I hypotrophy and the marked reduction in duration and amplitude of motor unit action potentials.

Ann'otrophic lateral sch,rosis Eight patients with amyotrophic lateral sclerosi: 'ALS) were studied. Extreme variability of onset firing rate was found, about equal numbers ofuNts firing at very high and low rates were presere Recruitment firing rate and variability v,ere also increased. As the number of motor units ~

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declined, single units firing at very high rates became more prevalent (Table II and Fig. 4).

Variation of firing rate Variance was normal in neuropathy and myopathy but markedly increased in ALS. The standard deviation of the interspike interv,:i of single units was also increased two to three fold in comparison with either normal, neuropathic or myopathic states. DISCUSSION

An attempt has been made to define criteria for abnormal firing rates in neuropathy, myopathy, and ALS which might be of use to the electrornyographer. In practical terms it is not difficult to assess frequency modes at onset and at recruitment. With a little cooperation from the patient it is not difficult to isolate single motor unit action potentials for evaluation of frequency and other characteristics. However, practical EMG without the use of a special purpose computer cannot go much beyond this point. Frequency analysis and muir•electrode techniques have been developed to increase the ability of the electromyographer to detect abnormality. Tokizane and Shimazu t1%4} have been able to class•t), motor units into tonic and kinetic types on the basis of variance of firing rate in relation to firing. Such techniques have not as yet been applied to the routine evaluation of neuromuscular disease. Despite the limitations of the method applied and the small population examined, certain differences between the disease states have been described. In neuropathy the electromyographer is more likely to encounter motor units firing at high rates at onset and recruitment. The existence of regions within the muscle in which this finding is present indicates abnormality. The finding most likely results from the location of the recording tip of the electrode in tile territory of "'type grouping". Firing characteristics of motor units have been related to muscle fiber type in pafientswith neuromuscular disease by recording from the site biopsied (Warmolts and Engel 1972). The presence of type grouping facilitates analysis and has supported the concept that type I motor units are tonic and type I1 units phasic in

400

firing characteristics. As a consequence of reinnervation, a region of muscle fibers innerv,~'~d by a single motoneuron exists which prevents recording of more distant recruited motor units. High onset firing rates can be explained on the basis of facilitation of surviving motoneurons occurring as the ratio of motoneurons to functioning muscle fibers decreases. Firing rate may also increase because surviving motoneurons have higher intrinsic rates or undergo adaptation to the denervation process. Motor unit firing rate may be normal in patients with myopathy. In other words, findings of decreased motor unit action potential duration and amplitude are more likely to precede changes in firing rate. Increased recruitment may also occur prior to evident change in firing rate. This accounts for the skewing toward lower firing rates at onset and recruitment. Not until a reduction in the number of motor units occurs would one expect to find an alteration in firing rate. The extreme variability of firing rate in ALS may result from altered motor unit control secondary to pyramidal tract involvement or from selective involvement of small tonic motoneurons wich normally initiate muscle contraction. The latter observation is compatible with the finding of Miglietta (1968) that a predominance of fast conducting large a::ons remains in patients with severe ALS. From the viewpoint of diagnosis, fi: ding motor units that vary greatly in firing rate at onset and recruitment would support the diagnosis of ALS. The finding of some motor units with low recruitment firing rates suggests an alteration in motor unit control perhaps at the spinal cord level. CONCLUSION

In patients with neuropathy and myopathy firing rate at onset and recruitment may be found to be significantly increased. However, firing rate tends to be higher in neuropathy than in myopathy. Firing rate may also be normal. Variance of firing rate is also normal. In ALS the prominent feature is an increase in the variance of mean firing rate at onset and recruitment. The findings described apply to patients with mild to moderate degrees of involvement.

J . H . PETAJAN SUMMARY

The rate at which motor units initiate firing and recruit additional units was determined in muscles at intermediate stages of involvement in 16 patients with neuropathy, 10 patients ,,ith myopathy and 8 patients with amyotrophic lateral sclerosis (ALS). Mean interspike intervals for onset and recruitment for the three pathological states were as follows: Neuropathy onset (0)=48 msec+ 17 (n=251); rec~itment (R)= 36 msec+ 12 (n= 144); myopathy (0)=65 msec +11 (n=131); (R)=45 msec+8 (n=73); ALS (0)=64 msec+_ 30 (n= 120); (R)=42 msec+22 (n=85): normal (O)= 132 msec+32 (n=693); (R)=90 msec+ 19 (n=693). Variance was normal for both neuropathy and myopathy. Units with quite high firing rates and with moderately high firing rates were more likely to be encoun' ~red in patients with neuropathy and myopathy respectively. In patients with ALS firing rates were more likely to be increased but variance was significantly increased both for mean firing rates and firing rates of single units. RESUME ETUDES ELECTROMYOGRAPHIQUES CLINIQUES DES MALADIES DE L'U NITE MOTRICE

La vitesse ~ iaquelle s'effectue l'initiation des d~charges des unit~s motrices et le recrutement d'unit~s additionnelles est d~termin~e dans le muscle ~ des stades interm6diaires d'6volution chez 16 malades atteints de neuropathie, 10 malades atteints de myopathie et 8 malades atteints de scl~rose lat&ale amyotrophique (ALS). Les intervalles moyens interpointes au stade initial et au stade de recrutement sont les suivants pour ces 3 6tats pathologiques" neuropathie, d6but (O)=48 msec+ 17 (n=251)" recrutement (R)=36 reset+ 12 (n=i44): myopathie [0)=65 msec+l! (n=131}" (R)=45 msec+ 8 (n= 73)" ALS (0)=64 msec+ 30 {n= 120), {R)=42 msec+22 (n=85)" normal (O)= 132 msec+32 (n=693): (R)=90 msec_+19 (n=693). La variance est normale aussi bran pour la neuropathie que la myopathie. Les unit6s qui pr6sentent des vitesses de d6charges tr6s 61ev6es et celles qui pr6sentent des vitesses de

CLINICAL EMG STUDIES

d~harge moyennement 61ev~es ont plus de probabilit~s d'apparition chez les malades atteints de neuropathie et de myopathie respectivement. Chez les malades atteints de ALS les vites~s de d&:harges ont plus de chances d'etre accrues mais la variance est significativement augment& h la fois pour les vitesses moyennes de d~harges et pour les vitesses de d&harges des unites isol~s. REFERENCES BUCHTHAL. F.. GULt~. C. and ROSE,XFALC~.P. Volume conduction of the spike of the motor unit potential investigated with a new type of multi-electrode. Acta physiol. scand., 195"7,3,~: 331-354. E.~GLV-. W. K. Selecti,,'¢ and nonselective susceptibility of

401 muscle fiber types. Arch. Neurol. f Chic.j. 1970, 22" 97-117. GRtMBV, L. and HAN~ERZ, J. Recruitment order of motor units on voluntary, contraction: changes induced by proprioceptivc afferent activity. J. Neurol. Neurosur.q. Psychiat.. 1~8., 31: 565-573. MIGLtE'rTA, O. Motor nerve fibers in amyotrophic lateral sclerosis. Amer. J. phys. Med.. 1968. 47: ! 18,rr124. P~.~o~,~. J. H. and PmLtp, B. A. Frequency control of motor unit action potentials. Eh'ctroencei,h. olin. Neurophysiol.. 1%9, 27: 66-72. ROMA~t'L. F. C. A. Enzymes in muscle. I. Histochemical studies of enzymes in individual muscle fibers. Arch. Neural. f C/t/b'. 2.1964,1 ! : 355- 368. TogtzA~t=. T. and Sru.~lazu. H. Fum'tional dit'/erentiati,ts . / human skeletal muscle. University of Tokyo Press. Tokyo. 1964. WARMOL~. J, R. and E~c~t-L. W. K. Open biops.~r electrom,,,ography. Arch. ,Veur,!. rChic./. 1972. 27:512 517,