J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.47.2.184 on 1 February 1984. Downloaded from Journal of Neurology, Neurosurgery, and Psychiatry 1984;47:184-189

Strength-duration curve: a measure for assessing sensory deficit in

WG FRIEDLI, M MEYER From the Department ofNeurology, University Hospital, Zurich, Switzerland

SUMMARY By using an isolated constant current stimulator producing true square-wave pulses, sensory strength-duration curves were obtained at various sites by percutaneous electrical stimu- lation. Strength-duration curves derived from normal groups were compared to those of patients with peripheral neuropathy. strength at sensory threshold was shown to be a reproduc- ible measure of sensory deficit, increasing parallel to the degree of axonal failure found by conventional methods. This may be useful as a complementary method in assessing peripheral neuropathy. The fact that both muscle and peripheral curve offers, to a certain extent, a useful method for assessing peripheral neuropathies. characteristically respond to electrical stimulation guest. Protected by copyright. allows a number of electrodiagnostic procedures. The relationship between the strength of a stimulus Methods and its duration for producing minimal excitation is Silver surface electrodes of 8 mm diameter filled with elec- expressed by the strenth-duration (S-D) curve.' The trode cream were taped about 2-5 cm apart over the skin standard type of S-D curve utilising visible muscle areas of interest. Skin preparation consisted of shaving the contraction has been applied to traumatic peripheral skin if necessary and cleaning it with ether and alcohol. nerve injuries and lower lesions.2-6 The distal electrode was connected to the cathode of an While electromyography provides extensive infor- isolated stimulation system consisting of an impulse mation as to the state of innervation of skeletal mus- generator (W-P Instruments Inc.) and a constant current cles, sensory conduction velocity often does not mir- stimulator (DISA 15 E 07). The latter was modified for ror the clinical state of the patient. For several external pulse width control and for extended pulse width reasons the quantitative examination of cutaneous of 50 ms (with approximately 10% pulse drop for 50 ms pulse duration). The amount of current in milliamperes sensation encounters serious problems.' Both affer- required to produce a minimally perceptible sensation was ent and efferent fibres have been studied by various determined for various durations of square-wave pulses electrodiagnostic techniques: nerve excitability has ranging from 0*05 to 50 ms (0-05, 006, 0-08, 0-10, 0-20, been determined by the strength of the true 0*50, 1-0, 2-0, 5-0, 10-0, 20*0, 50 0 ms). For each of the 12 square-wave stimuli required to elicit a barely vis- pulse durations detection thresholds were obtained by a ible nerve at a recording site proxi- method of descending limits, continuously decreasing from mal to the stimulus.8- " Stimulus strength at sensory a level at which the subject had a minimal sensation. Elec- threshold has been shown to be more reproducible trical stimuli were given at a rate of 0-5/s and were dis- http://jnnp.bmj.com/ than the one just evoking a sensory action poten- played on an oscilloscope screen in front of the subject. tial.'2 Sensory S-D curves obtained with behavioural Usually three independent measurements were performed on each subject for each pulse duration tested, the series psychophysical techniques have matched those starting with 50 ms stimuli. S-D curves were obtained by obtained by electrophysiologic procedures.'3 How- plotting current intensities producing a just perceptible ever, few clinicians have used cutaneous electrical sensation against stimulus duration. stimulation for assessing peripheral nerve function'4 For each stimulation site studies were performed on a and clinical feasibility has not been apparent in the control group and a patient group. Each control group past. According to our findings the sensory S-D consisted of 10 to 12 healthy subjects without history or on September 27, 2021 by clinical evidence of neuromuscular disease. To ascertain the reproducibility of normal curves the same subject was Address for reprint requests: Walter G Friedli, Neurologische tested in 10 independent series of measurements on suc- Universitatsklinik Kantonsspital, CH-4031 Basel, Switzerland. cessive days. During the measurements skin temperature was controlled by means of a digital thermometer and kept Received 23 June 1983. Accepted 2 August 1983 constant by an infrared lamp within the range of 1°C. 184 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.47.2.184 on 1 February 1984. Downloaded from

Strength-duration curve: a measure for assessing sensory deficit in peripheral neuropathy 185 Results lation site is shown in fig 1B for the same subject. While being in the same range, the threshold values S-D curves were surprisingly reproducible in healthy showed smaller standard deviations when compared subjects on successive trials. The task was more with the whole group, even if independent meas- difficult for some of the patients depending on the urements were performed on different days. A simi- degree of sensory impairment, especially if paraes- lar degree of reproducibility was observed in indi- thesiae were present. The subjects compared the vidual subjects for the cutaneous field of the median sensation produced by electrical stimuli to the sensa- or ulnar nerve. tion of being tapped, that is, a stimulus tactile in Temporal summation properties are represented quality. by the product of current strength and duration at In a first series of experiments normal S-D curves threshold levels (stimulus energy in microcoulombs) were obtained at various stimulation sites. In one as a function of stimulus duration (fig 1B). Accord- group of 12 healthy subjects sensory thresholds ing to the Bunsen-Roscoe law or Bloch's law were measured bilaterally in the cutaneous field of stimulus energy at threshold levels remains constant the superficial peroneal nerve. The electrodes were for stimulus durations less than the "critical dura- placed on the proximal dorsum of the foot following tion" specific for a sensory modality. For vision, the tendon of extensor hallucis longus. Average reciprocity between luminance and time at threshold thresholds across trials and different subjects are has been found to be limited to durations of about presented separately for the two sides of the body in 10 ms in the paramacular region'5 while the critical fig 1A. A rapid decrease of the threshold current duration was found to be considerably longer for with increasing stimulus duration up to 0-5 to 1-0 ms other sensory modalities. In agreement with Roll- was observed while there was little change of man's findings our data suggest a very small critical

threshold current with longer stimuli. The minimal duration of less than 0-10 ms for cutaneous electri- guest. Protected by copyright. current required to produce cutaneous sensation cal stimulation. The absence of a total temporal also with very long current (rheobase) was achieved summation in our graphs was probably due to the by pulse durations of approximately 10 ms. Sensory fact that minimum pulse duration was limited to thresholds were found to be lower for the left com- 0-05 ms. Different degrees of partial temporal pared to the right side of right-handed people in summation were found for successive periods, the both upper and lower extremities. Although the dif- first extending to about 0.10 ms, and a second to ference in absolute values may be disregarded, this about 1-0 ms. There was no temporal summation for asymmetry was a consistent finding in our normal pulse durations beyond 10 ms and the function had subjects. a slope of 1-0. Reproducibility of S-D curves for the same stimu- To allow comparison between different stimula- 0 0) - o E 7-

a, 6- 3 V - cn -+-!5- 11 X E 3

c 4- http://jnnp.bmj.com/ (I) J 3 - Ei 2- 1- ICI I,,,C ,,, 005 020050 20 50 10 20 50 (005 020050 20 5010 20 50 c Stimulus-duration (ms) on September 27, 2021 by Fig 1 Strength-duration curve for rectangular current pulses on the dorsum ofthe right (-) and left (0) foot, ie in the cutaneous field ofthe superficial peroneal nerve. Rheobase (R) and chronaxy (C). (A) Average of12 healthy subjects ranging in age from 25 to 41 years. (B) Reproducibility ofS-D curve for 1 subject of27 years, same stimulation site. Average of IO series ofindependent measurements performed on successive days. Energy necessary for minimal sensation as a function ofpulse duration (O in B), showing temporal summation properties. J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.47.2.184 on 1 February 1984. Downloaded from

186 Friedli, Meyer

14 - 13-

0, -D 12 - o 11- aE E ~,15- a, 10 - 3 cn E _ 'a g- x RA 2 8- 0) 10- n

5- guest. Protected by copyright.

R N -- 0- 005 010 020 050 10 20 50 10 20 50 Stimulus- duration (ms) Fig 2 S-D curves (superficial peroneal nerve) in neuropathic disease compard to normals offig I (hatched 005 010 0.50 10 20 50 10 20 50 area: mean + I standard deviation). Individual curves from Stimulus- duration (ims) patients with angiopathic neuropathy (A), alcoholic (B), uraemic (C) and diabetic (D) (details in Fig 3 S-D curves for the median nerve (stimulating table). Compare marked differences ofrheobases and the cathode on the index finger). Average of8 healthy subjects similar chronaxy values for the different conditions. from 26 to 41 years (-) for both hands (n = 16). Note the Upper graph: threshold energy as a function ofpulse difference ofabsolute threshold values between median and duration for patient B and healthy group showing superficial peroneal nerve (fig 1). Mean and standard differences in temporal integration properties between the deviations of6 patients (0) with severe carpal tunnel syndrome (sensory action potentials ofsmall amplitude two. markedly delayed, ifrecordable at all). Comparison ofthe two threshold energy functions reveals differences in absolute values and temporal integration properties. http://jnnp.bmj.com/ tion sites on the same subject, threshold measure- Sensory S-D curves were obtained from 25 ments were performed by stimulating in the cutane- patients with various kinds of peripheral ous fields of the sural, superficial peroneal as well as neuropathy. Some examples are given for stimula- lateral femoral cutaneous nerve. Compared with the tion in the cutaneous field of the superficial peroneal area of the superficial peroneal nerve lower nerve in fig 2 (see table for case descriptions). S-D thresholds were found on the external border of the curves of the pathological subject groups are com- foot and even lower values were found on the lateral with the of normal subjects in fig 1. The pared group on September 27, 2021 by aspect of the thigh in this group of healthy subjects. rate of climb in the pathological curves was larger For all subjects there was a consistent rank of abso- from right to left compared to that of the normal lute thresholds according to the stimulation site; the curves. However, even if present, this variation of values of the whole group were not significantly dif- slope was too small to be of any practical relevance. ferent (p < 0O5 to p < 005 for short stimuli up to In general, the sensitivity threshold in terms of 0 10 ims). stimulus current was raised over the whole range of J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.47.2.184 on 1 February 1984. Downloaded from

Strength-duration curve: a measure for assessing sensory deficit in peripheral neuropathy 187 Table Case descriptions (patients offigure 2). Rating ofpathological conditions: 0 normal, I mild, 2 moderate, 3 severe

Z1 ti "I 4 1:: t BS 9 t E t s

A 55 M 3 2 3 2 3 painful 1 1 2 2 2 2 dysaesthesia Wegener's on both granulomatosis feet B 33 F 3 3 3 1 2 bilateral 1 1 2 2 3 3 foot drop, Alcoholic unable to walk C 35 M 2 1 1 1 2 3 2 2 1 0 1 Uraemic (chronic renal failure) D 66 M 2 1 0 2 2 bilateral 2 2 1 1 0 1 entrapment Diabetic neuropathies of ulnar and median nerve guest. Protected by copyright.

0

ma

5- http://jnnp.bmj.com/

100 ms ms ms Fig 4 (A) 41-year-old male. Traumatic partial lesion ofthe right median nerve in the distal forearm 4 months before examination. Severe sensory impairment to all modalities in the index (-), markedly less in the middle finger

(0). No sensory action potentials from digit to wrist. Note the difference between S-D curves on the two fingers which on September 27, 2021 by is in accordance with the clinical findings. (B) 24-year-old female, suffering from symptoms ofa moderate carpal tunnel syndrome (sensory conduction of39 mis, small sensory action potential of4 ,uV). S-D curve on the right index finger before (0) and after (-) paraneural infitration with an anaesthetic into the carpal tunnel (when no action potential could be recorded any more). (C) S-D curves (index finger) ofa 60-year-old malepatient with severe carpal tunnel syndrome before (0) and 3 months after (-) surgical decompression ofthe right median nerve. Note the difference ofrheobase before (no sensory action potential, distal motor latency of6.3 ms) and after surgery (markedly delayed action potential of2 5 ,uV, motor latency of5 1 ms). J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.47.2.184 on 1 February 1984. Downloaded from

188 Friedli, Meyer pulse duration as is shown by the curve shifting with subnormal to normal nerve conduction and the upward and to the right. This shift was also found for electromyographic equivalents of a severe axonal stimulus energy at threshold levels (fig 2, upper lesion. On the other hand, the findings in patients C graph): the patient curve shows an overall rise of and D are characterised by motor and sensory con- threshold energy. A comparison of the slopes of the duction defects with little evidence of denervation. two energy functions revealed changes in temporal This is in agreement with the fact that S-D curves summation properties. In contrast to healthy sub- are hardly impaired in chronic entrapment jects, a reciprocity between stimulus strength and neuropathies (for example, the median nerve in time at threshold levels was found for pulse dura- fig 4B) but affected in proportion to the incidence of tions up to 0*10 ms in subjects with severe axonal lesion (for example, patients of fig 3). neuropathy. Hence, not only partial temporal sum- Discontinuities in the classical S-D curve result mation was extended to longer pulse durations but from the difference in excitability threshold between also the critical duration was prolonged in the muscle and nerve tissue. Therefore, sensory S-D pathological case. curves representing properties of afferent nerve S-D curves for the median and ulnar nerve were fibres are expected to be smooth also in case of par- obtained by stimulating the distal phalanges of the tial denervation. Pathological conditions are charac- index and middle finger or of the little finger respec- terised by an over-all increase in threshold excitabil- tively. Normal curves were compared with those ity providing both a shift of the curve and changes in found with various nerve lesions. Even if there was temporal integration properties. There are various clear clinical and electroneurographic evidence of possible explanations for this behaviour; it may be entrapment neuropathy, sensitivity thresholds often due to a threshold increase of the A fibres, or did not reflect the pathological condition. However, stronger stimuli may be required to recruit an S-D curves were significantly altered with a severe increasing number of A fibres for minimal sensation. guest. Protected by copyright. carpal tunnel syndrome, characterised by marked Another possibility is that stronger pulses may pro- conduction deficits, electromyographic abnor- vide excitation of other types of afferent fibres in malities in the thenar muscles or loss of the sensory addition to A fibres. This is suggested by the changes action potential (fig 3). In these cases, serial S-D in temporal summation properties. However, our curves after surgical decompression of the median results cannot give additional information about the nerve displayed a functional improvement (fig 4C). elements of sensory S-D curves. There was also a clear relationship between sensory Assessment of sensory impairment is part of the deficits due to traumatic nerve lesions and the clinical evaluation of peripheral neuropathies. For behaviour of sensitivity thresholds as a function of several reasons quantification of cutaneous sensa- stimulus duration (fig 4A). tion by clinical examination is inaccurate and calls for methods of measurement using "adequate" Discussion stimuli.7 24-26 Both sensory S-D curves and quantita- tive sensory tests are complementary to the clinical Together with the clinical and electrodiagnostic evaluation of peripheral nerve disorders. The fact evaluation of a peripheral neuropathy, the systema- that the sensory threshold is mostly affected with tic examination of sensory strength-duration curves axonal lesions suggests a valuable complement to provides useful help in diagnosis. conventional electrodiagnostic techniques. The characteristics of psychometric functions for The simplicity of the method (no complex record- electrocutaneous stimuli have suggested that cur- ing and averaging equipment) represents a further http://jnnp.bmj.com/ rent pulses bypass the receptors and directly excite advantage in comparison with electroneurographic sensory fibres"6 17 as supported by other results.'8-20 procedures. However, the isolated constant-current Moreover, temporal integration properties of stimulator has to be capable of producing true psychophysical S-D curves were consistent with square-wave stimuli over a wide range of pulse dura- stimulation of large A-fibres by electrocutaneous tions. Moreover, the subject tested must be attentive pulses.'6 According to previous findings fibres with and cooperative during the behavioural assessment large diameter have faster velocities and lower of peripheral nerve function. The examination can thresholds than fibres with small diameter.2123 be reduced to a few representative pulse-durations. on September 27, 2021 by The correlation of the S-D curve with pathologi- The amount of current of infinite duration required cal clinical and electrodiagnostic findings in the same to produce minimal sensation (rheobase) represents patient provides further information as to the a valuable measure and approximates stimulus dura- anatomical substrate tested by the psychophysical tions of 10 to 50 ms. The chronaxy, that is the dura- technique. Both patients A and B of fig 2 had a tion of a threshold stimulus of twice the rheobase, symmetrical motor and sensory polyneuropathy proved to be less informative, expecially because it J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.47.2.184 on 1 February 1984. Downloaded from

Strength-duration curve: a measure for assessing sensory deficit in peripheral neuropathy 189 is based on calculation. Temporal integration prop- nerve in patients with normal motor nerve conduction erties and critical duration are useful parameters but velocities. Neurology (Minneap) 1973;23:78-83. 12 Buchthal F, Rosenfalck A. Evoked action potentials and measurements in the low range of require several conduction velocity in human sensory . Brain stimulus duration. For each laboratory S-D curves Res 1966;3:1-122. must be based on normal values (specific for age and 13 Roilman GB. Behavioral assessment of peripheral nerve stimulation site). However, bilateral comparison function. Neurology (Minneap) 1975;25:339-42. within the same subject might be indicative of 14 Bourguignon G. La chez l'Homme. Etude de mononeuropathy. Physiologie Generale (normale et pathologique) des Systemes Neuro-musculaires et Sensitifs. Paris: Mas- The authors thank Dr Dorothea Weniger for her son, 1923. help in preparing this manuscript and Mr Joseph 15 Battersby WS, Schuckman H. The time course of tem- Muller for photographic work. poral summation. Vision Res 1970;10:263-72. 16 Roilman GB. Electrocutaneous stimulation: Psycho- metric functions and temporal integration. Percept References Psychophys 1969;5:289-93. 7 Roilman GB. Detection models: Experimental tests with Wynn Parry CB. Strength-duration curves. In: Licht S, electrocutaneous stimuli. Percept Psychophys 1969; ed. Electrodiagnosis and Electromyography. 3rd ed. 5:377-80. New Haven: Elizabeth Licht, 1971:241-71. 18 Gildemeister M. Untersuchungen uber die Wirkung der 2 Adrian ED. The electrical reactions of muscles before Mittelfrequenzstrome auf den Menschen. Pfugers and after . Brain 1916;39:1-33. Arch Ges Physiol 1944;247:366-404. 3Pollock LJ, Golseth JG, Arieff AJ. Strength-frequency 19 Higgins JD, Tursky B, Schwartz GE. Shock-elicited pain curves in electrodiagnosis of experimentally produced and its reduction by concurrent tactile stimulation.

peripheral nerve lesions. Surg Gynecol Obst Science 1971 ;172:866-7. guest. Protected by copyright. 1945;80:235-42. 20Hawkes GR. Cutaneous discrimination of electrical 4 Newman HW, Livingstone WK. Electrical aids in prog- intensity. Am J Psychol 1961;74:45-53. nosis of nerve injuries. J Neurol Neurosurg Psychiatry 21 Blair EA, Erlanger J. A comparison of the characteris- 1947;10:1 18-21. tics of through their individual electrical 5 MacKenzie IG. Electrical reactions of muscle in responses. Am J Physiol 1933;106:524-64. poliomyelitis. Proc R Soc Med 1949;42:488-90. 22 Gasser HS, Grundfest H. diameters in relation to 6 Wynn Parry CB. Electrical methods in diagnosis and the spike dimensions and the conduction velocity in prognosis of peripheral nerve injuries and mammalian A fibres. Am J Physiol 1939;127:393- poliomyelitis. Brain 1953;76:229-65. 414. Dyck PJ. Quantitation of cutaneous sensation in man 23 Wiederholt WC. Stimulus intensity and site of excitation (chap 22). In: Dyck PJ, Thomas PK, Lambert EH, in human median nerve sensory fibres. J Neurol eds. Peripheral Neuropathy Vol. 1. Philadelphia: Neurosurg Psychiatry 1970;33:438-41. Saunders, 1975:465-79. 24 Dyck PJ, Schultz PW, O'Brien PC. Quantitation of Heckmann JR. Excitability curve: a new technique for touch-pressure sensation. Arch Neurol 1972;26: assessing human peripheral nerve excitability in vivo. 465-73. Neurology (Minneap) 1972;22:224-30. 25 Fruhstorfer H, Lindblom U, Schmidt WG. Method for Powers RE, Swick HM, McQuillen MP. Human nerve quantitative estimation of thermal thresholds in excitability. J Neurol Neurosurg Psychiatry 1978; patients. J Neurol Neurosurg Psychiatry 1976;39: 41:642-8. 1071-5. Veale JL, Mark RF, Rees S. Differential sensitivity of 26 Lindblom U. Quantitative testing of sensibility including motor and sensory fibres in human ulnar nerve. J pain (chap 8). In: Stalberg E, Young RR, eds. Neurol Neurosurg Psychiatry 1973;36:75-86. Neurology, vol 1: Clinical neurophysiology. London: http://jnnp.bmj.com/ Wright EA, McQuillen MP. Hypoexcitability of ulnar Butterworth, 1981:167-90. on September 27, 2021 by