KAUNAS UNIVERSITY OF MEDICINE
JOVITA ŠVILPAUSKĖ
A study of peripheral nerve disorders using
the cutaneous silent period
Doctoral dissertation
Dissertation has been prepared at Kaunas University of Medicine during the period 2001 – 2005.
Scientific supervisor:
Assoc. prof. dr. Nerija Vaičienė (Kaunas University of Medicine, biomedical sciences, medicine – 07B)
Research advisor:
ACKNOWLEDGEMENTS
This work and my specialization as a neurophysiologist, have been possible thank to the collaboration agreement between Medical Faculty of Geneva University and Kaunas University of Medicine.
I express my sincere gratitude to Professor Michel R. Magistris from Geneva University for teaching me electroneuromyography from the very first steps to the advanced level, for the help in understanding secrets of electroneuromyography and for giving me the opportunity to work in one of the best electroneuromyography laboratories. He suggested the topic of this study to me, has guided my scientific work and publications. His skill and experience in electrophysiology and clinical research, encouragement,
enthusiasm, patience and working capacity have been the greatest school for both my scientific and practical work.
I am very grateful to Assoc. prof. dr. Nerija Vaicienė from Neurology
Department, Kaunas University of Medicine, for the possibility to study in doctorantura program and carry on studies in Geneva, for supervising my research, for her support in every matter and for her friendship.
I express my gratitude to Assoc. prof. dr. Valius Pauza who was the first to encourage me to study electroneuromyography.
I thank Dr. Andre Truffert, University Hospital of Geneva, for the examinations of patients with polyneuropathies and my many colleagues and friends of the Departments of Neurology in Kaunas and Geneva for their help in my endeavors to achieve experience in neurology, and for having played the role of healthy controls.
My cordial thanks are addressed to Assoc. prof. habil. dr. Daiva Rastenytė, for her invaluable advices, and to Egle Sepetauskiene for her expert help with statistics.
I am very grateful to my family for their support during all years of my studies and to my little daughter Indre who needed to be very patient during her first months of life.
CONTENT
ACKNOWLEDGEMENTS... 3
ABBREVIATIONS ... 6
1. INTRODUCTION ... 7
2. AIM AND OBJECTIVES OF THE STUDY ... 11
2.1. Aim of the study... 11
2.2. Objectives... 11
3. NOVELTY, SCIENTIFIC AND PRACTICAL SIGNIFICANCE OF THE STUDY .. 12
3.1. Novelty and scientific significance of the study ... 12
3.2. Practical significance of the study... 13
4. REVIEW OF THE LITERATURE ... 14
4.1. Mechanisms of the cutaneous silent period (CuSP)... 14
4.1.1. Afferent part of the CuSP... 14
4.1.2. Central processing of the CuSP... 15
4.2. Methodology ... 17
4.3. Results ... 20
4.4. CuSP clinical application ... 23
4.4.1. CuSP in disorders of the peripheral nervous system... 23
4.4.2. CuSP in disorders of the central nervous system ... 25
5. SUBJECTS AND METHODS OF THE STUDY ... 26
5.1. Subjects ... 26
5.2. Methods... 29
6. RESULTS OF THE STUDY ... 34
6.1. CuSP in normal controls ... 34
6.1.1. Effect of stimulus intensity on CuSP ... 34
6.1.2. CuSP in different muscles on hands and feet... 48
6.1.3. CuSP from same limb but different innervation ... 48
6.1.4. CuSP from contralateral limbs ... 50
6.2. CuSP in patients ... 52
6.2.1. CuSP in carpal tunnel syndrome patients... 52
6.2.2. CuSP in patients with polyneuropathies... 62
7. DISCUSSION ... 76 8. CONCLUSIONS... 86 9. PRACTICAL GUIDELINES... 87 10. REFERENCES ... 89 11. LIST OF PUBLICATIONS ... 100 12. ANNEX... 101
ABBREVIATIONS
ADM - abductor digiti minimi APB - abductor pollicis brevis
CMAP - compound muscle action potential CTS - carpal tunnel syndrome
CuSP - cutaneous silent period EMG - electromyography n.s. - not statistically significant PNP - polyneuropathy
RIII - nociceptive flexion reflex SD - standard deviation
1. INTRODUCTION
Nerve conduction studies performed routinely in electroneuromyography laboratories deal mainly with large myelinated fast conducting nerve fibers. A reliable method allowing the study of small peripheral nerve fibers (i.e. A delta and C) would be of interest. However, neurography of such fibers cannot be performed easily and requires indirect studies. Methods for assessing small nerve fiber function are few, and different tests are needed for the evaluation of both small myelinated and unmyelinated nerve fibers.
Sympathetic skin response studies the galvanic response involved in sweating to assess the
efferent sympathetic C fibers indirectly (Shahani et al. 1984, 1990; Schüller et al. 2000; Vetrugno et al. 2003). The test is simple and can be performed rapidly, but it is not sensitive and of doubtful clinical relevance (Lacomis 2002). Quantitative sensory testing assesses thermal sensations served by thinly myelinated A delta fibers and unmyelinated C fibers (Gruener and Dyck 1994; Yarnitsky 1997; Zaslansky and Yarnitsky 1998; Meier et al. 2001; Dyck and O’Brien 2002; Magda et al. 2002; Stewart and Freeman 2002; Chong and Cros 2004). The test, that requires dedicated equipment, depends on the participation of the subject tested (Shy et al. 2003). Quantitative sudo-motor axon reflex test assesses postganglionic sympathetic cholinergic sudo-motor function. It is sensitive to detect a small fiber neuropathy, but it also requires a special equipment that is not widely available
(Holland et al. 1998; Riedel et al. 1999; Shy et al. 2003). Skin biopsy is a new method for studying intraepidermal nerve fibers (McCarthy et al. 1995; Kennedy et al. 1996; McArthur et al. 1998; Kennedy and Wendelschafer-Crabb 1999; Griffin et al. 2001). Epidermal fibers relate entirely to the dorsal root ganglia, they are presumed to represent the terminals of C, and perhaps also of A delta nociceptors (Kennedy and Wendelschafer-Crabb 1993;
Hermann et al. 1999). Skin biopsy is a minimally invasive method. It is sensitive and can be performed from multiple sites, but for wider clinical use, it is hampered by complicated histological techniques and by the need for specific equipments and expertise (Shy et al. 2003). Small diameter nociceptive fibers of very slow conduction velocity may be studied electrophysiologically via the assessment of the nociceptive flexion reflex (the RIII
interest and the close relationship between the threshold to obtain the RIII response and that of the pain sensation experienced by the subject is extensively serving the purpose of pharmacological studies (Desmeules et al. 2000; Willer et al. 2000; Skljarevsli and Ramadan 2002). However, RIII is readily available only from a few limb muscles; it has mainly been studied from the biceps femoris muscle following sural nerve stimulation. The
cutaneous silent period (CuSP) is another test available for studying nociceptive fibers. It is
a simple noninvasive method that appeared, from the literature and from the pilot studies which we conducted, to be available from many muscles (if not from all) of both upper and lower extremities. It can be obtained using standard electromyography (EMG) equipment. The CuSP is one among several methods that use the principle of inhibiting an ongoing muscle contraction. The silent period consists in a transient arrest of the EMG voluntary activity that occurs in response to an electrical stimulus. It was described for the first time by Hoffmann in 1922 (cited by Angel et al. 1966; Higgins and Lieberman 1968; Laxer and Eisen 1975; Uncini et al. 1991). The silent period obtained in response to the stimulation of either a sensory nerve, yielding the CuSP (Fig. 1), or of a mixed (sensory and motor) nerve, yielding the “mixed nerve silent period” (Leis et al. 1991; Leis 1993; Ford et al. 1995; Shefner and Logigian 1998). Both require painful stimuli and subject cooperation for volitional contraction of the target muscle. The masseter inhibition reflex is a silent period obtained by stimulating a sensory nerve (mental nerve) during forceful contraction of masseter muscles (Godaux and Desmedt 1975; Ongerboer de Visser and Goor 1976; Valls-Sole et al. 1990; Cruccu et al. 1991, 1998; Floeter 2003). A “cortical silent period” is evoked by transcranial stimulation (Calancie et al. 1987; Inghilleri et al. 1993; Uncini et al. 1993a; Kofler et al. 1998, 2001; Daskalakis et al. 2003; Orth and Rothwell 2004; Kim et al. 2005). The usual abbreviation of the cortical silent period being “CSP” or “CoSP” in literature we decided to abbreviate the cutaneous silent period “CuSP”. The mixed nerve silent period, masseter inhibition reflex and cortical silent period differ in many respects from the CuSP. They will not be considered further in this study, which will deal only with the CuSP.
Although the silent period is known since 1922, its precise physiological mechanism remains uncertain, and data about CuSP in normal subjects and in patients with peripheral nerve injuries are still scare. An accumulation of evidence is in favor of the role
A.
CuSP latency CuSP duration
B.
CuSP latency CuSP duration
FIGURE 1. Normal cutaneous silent periods (CuSP) elicited from tibialis anterior muscle during maximal voluntary contraction and following sural nerve stimulation. A) four successive recordings; B) superimposition of the four recordings (calibration 200 µV/50 ms).
of small diameter afferents in producing the CuSP. In spite of this, to date, abnormalities of CuSP have not been demonstrated in patients with dysfunction of small diameter cutaneous afferents. Furthermore, it is not clear which parameter of the CuSP would be most sensitive to partial abnormalities, changes in latency, duration, or of the „quality“ of the silence. To assess the clinical utility of CuSP, and to better understand the role of small diameter afferents CuSP should be assessed in patients who have a neuropathy.
A number of groups have studied the CuSP. These groups have used different protocols and methods of both stimulating and recording, leading to results that are not always easy to compare and interpret.
2. AIM AND OBJECTIVES OF THE STUDY
2.1. Aim of the study
The aim of the study is to evaluate small diameter A delta nerve fibers
function using the CuSP in normals and in patients with both focal (carpal tunnel syndrome (CTS)) and generalised (polyneuropathies (PNP)) peripheral nerve disorders.
2.2. Objectives
1. To determine the CuSP normal values by age, gender, side, height and weight in healthy controls.
2. To study the topography and extension of the CuSP by changing recording and stimulating sites in healthy controls.
3. To evaluate the CuSP in patients with CTS of different severity and to compare these results with those of healthy controls.
4. To estimate the CuSP onset latency and duration in relation with median nerve evoked compound muscle action potential (CMAP) amplitude, distal latency and conduction velocity in patients with CTS.
5. To evaluate the CuSP in patients with PNP of different types and to compare these results with those of healthy controls.
6. To estimate the CuSP onset latency and duration in relation with median nerve evoked CMAP amplitude, distal latency and conduction velocity in patients with PNP.
3. NOVELTY, SCIENTIFIC AND PRACTICAL SIGNIFICANCE OF THE STUDY
3.1. Novelty and scientific significance of the study
The CuSP, which has not been studied in Lithuania previously, has several innovative aspects, it:
- offers a new approach to the study of small diameter A delta fibers;
- provides normal values of the CuSP for different stimulation and recording sites from the four limbs;
- provides new information concerning the physiology of the CuSP;
- complements findings of others concerning the pathophysiology of the CuSP in neuropathies.
For the first time CuSP was recorded from many muscles, from upper (7 muscles) and lower extremities (4 muscles), after painful distal cutaneous stimulation of the same, or of other limbs in 50 normal volunteers (97 sites).
For the first time CuSP was evaluated in many patients with CTS (80 patients; 160 sides) and PNP (140 patients; 140 sides), and findings were compared and related to data of conventional neurography.
This study helps to introduce the CuSP to evaluate small fibers in clinical testing.
3.2. Practical significance of the study
Conventional routine nerve conduction studies and needle EMG evaluate the function of large diameter, rapidly conducting motor and sensory myelinated nerve fibers, but fail to assess the function of small fibers. In patients with small fiber neuropathies the discrepancy of subjective sensory complaints to the absence of conventional objective signs may lead to erroneous diagnosis and treatments. Thus assessment of small fibers and
identification of syndromes involving small fibers may have important implications for our patients.
This study provides objective data about CuSP in normal subjects, and allows assessing small diameter A delta nerve fibers in patients with peripheral nerve disorders. As CuSP recording is a relatively simple electrodiagnostic procedure, it could be applied in daily practice in electroneuromyography laboratories.
4. REVIEW OF THE LITERATURE
4.1. Mechanisms of the CuSP
The physiological mechanisms generating the CuSP remain uncertain, but most investigators agree that it is a spinal inhibitory reflex (Caccia et al. 1973; Uncini et al. 1991; Leis et al. 1995; Inghilleri et al. 1997). The afferent pathway and spinal processing yielding the CuSP have been the matter of several studies and conflicting hypothesis.
4.1.1. Afferent part of the CuSP
The afferent impulses which generate the CuSP are carried primarily by small diameter slowly conducting A delta fibers (Kranz et al. 1973; Uncini et al. 1991; Leis et al. 1992; Shefner and Logigian 1993a; Inghilleri et al. 1997) as classified by Erlanger and Gasser (1937). A delta fibers correspond to group III afferents in Lloyd’s (1943) numeral classification (Table 1). The diameter of these thinly myelinated fibers ranges from 1 to 6 μm. Their excitation requires intense stimuli and they conduct nociceptive impulses at 13-20 m/s (Kranz and von der Heydt 1973; McLellan 1973; Uncini et al. 1991; Leis 1994). Some investigators proposed that other fibers also contribute to produce the CuSP. Caccia et al. (1973) suggested that the early part of the CuSP is mediated by group III fibers (A delta), and that the late part of the CuSP results from the activity of group II fibers (A beta) connected in particular to cutaneous mechanoreceptors of the finger tips. Others have proposed that large diameter fibers that do not convey painful impulses may also participate in producing the CuSP (Syed et al. 2000, Serrao et al. 2001, Kofler 2003).
Table 1. Classification of afferent nerve fibers
Afferent nerve fibers by Erlanger
and Gasser by Lloyd
Myelination Diameter µm Velocity m/s Function A alpha Ia Ib +++ +++ 10-20 10-20 50-120 50-120 muscle spindle Golgi-tendon organ, touch, pressure A beta II ++ 4-12 25-70 muscle spindle, touch,
pressure
A delta III + 1-6 13-20 pain, temperature
(cold sensation)
C IV - <1 <2 pain, temperature
(warm sensation), autonomic
4.1.2. Central processing of the CuSP
The central mechanism of the CuSP is not known. Theoretically, the CuSP may result from the: inhibition of the spinal motoneuron pool by Renshaw cells (Uncini et al. 1991); presynaptic inhibition of corticospinal fibers, or of spinal interneurons that relay the cortical command to the spinal motoneuron pool (Leis et al. 1995, 1996); postsynaptic inhibition of the spinal motoneuron pool (Inghilleri et al. 1997; Manconi et al. 1998; Logigian et al. 1999).
Inhibition of the motoneuron pool by Renshaw cells. As Renshaw cells are known to be activated after small fiber input to the spinal cord (Piercey and Goldfarb 1974), Uncini et al. (1991) proposed that Renshaw cells activated directly by high threshold nociceptive cutaneous afferents may mediate the motoneuron inhibition. These authors consider that
cutaneous afferent inputs are excitatory in their action, and that the inhibition they exert is mediated through inhibitory interneurons.
Presynaptic inhibition of corticospinal fibers or of spinal interneurons. Leis et al. (1995, 1996) assessed spinal motoneuron excitability during the CuSP using F and H responses. They observed that during isometric contraction F wave amplitude and persistence are unchanged during the CuSP interval, whereas H reflex is markedly suppressed. At rest, F wave amplitude and persistence are increased during the “virtual” CuSP interval, whereas H reflex is not elicitable. They concluded that the CuSP is not caused by the refractoriness of the spinal motoneurons, since they remain excitable to an antidromic volley during the CuSP interval. Eventually they proposed that the spinal mechanism responsible for the CuSP consists in a presynaptic inhibition of corticospinal fibers, or in an inhibition of spinal interneurons, or in a combination of both.
Postsynaptic inhibition of the motoneuron pool. Other investigators, who explored the physiological mechanisms of the CuSP using F and H waves, and motor evoked potentials, concluded differently. They showed that F responses are inhibited by cutaneous stimuli, most likely by postsynaptic inhibition of motoneurons (Logigian and Shahani 1986; Inghilleri et al. 1997). The time course of inhibition was examined by the changes in H reflex (Logigian and Shahani 1986; Manconi et al. 1998) and by applying motor evoked potentials during the CuSP (Manconi et al. 1998). Both H reflex and motor evoked potentials were inhibited during the CuSP suggesting that postsynaptic inhibition of the motoneurons plays a major role. Logigian et al. (1999) analyzed the CuSP in patients with complete spinal cord injuries by measuring the effect of high intensity cutaneous stimuli on spinal motoneuron excitability using routine H reflex methodology. They showed that the spinal cord below a complete spinal cord injury contains the reflex circuitry necessary to generate the CuSP. This suggests that the afferent volley subserving the CuSP at one spinal segment ascends and descends to numerous spinal (and brainstem) levels, resulting in supra- and infra-segmental inhibition of motoneurons. A descending supraspinal input from the sensorimotor cortex appears to have a net facilitory effect on an inhibitory spinal reflex that in turn mediates the CuSP at the segmental level. Interruption of this descending input results in a net reduction of the inhibitory effect of the cutaneous stimulation on the
abnormalities in patients presenting with various movement disorders. To summarize, the latter studies suggest that spinal motoneurons inhibition is postsynaptic and mediated by spinal inhibitory interneurons.
Leis (1998) proposed that the CuSP may result from a combination of the above discussed pre- and postsynaptic mechanisms.
4.2. Methodology
CuSPs studies are not standardized. Different laboratories used different stimuli, recording and measurement protocols. This probably explains the variability of the results.
For the CuSP study some groups investigated the subjects while seated (Pullman et al. 1996; Floeter et al. 1998; Manconi et al. 1998), with hands maintained in a semipronated position, and elbows fixed and flexed at 110 degrees, and shoulders abducted about 30 degrees (Pullman et al. 1996). Other volunteers hands were immobilized in Plasticine (Stephens and Usherwood 1976) or strapped into a Plexiglas frame (Manconi et al. 1998, Syed et al. 2000). Some controls laid supine (Logigian et al. 1999).
Recording. The CuSP can be recorded using any EMG apparatus, from muscles following a painful cutaneous stimulus. The EMG activity and CuSP are recorded with surface electrodes routinely used for nerve conduction studies and fixed in a belly-tendon position. The ground electrode is fixed between the stimulating and recording electrodes.
Filters. For the CuSP studies the investigators used different low and high filters settings: 2 Hz to 10 kHz (Caccia et al. 1973), 20 Hz to 10 kHz (Kofler et al. 2003a), 30 Hz to 3 kHz (Pullman et al. 1996; Rossi et al. 2000, 2003; Serrao et al. 2001), 20 Hz to 2 kHz (Manconi et al. 1998; Syed et al. 2000), 10 Hz to 3 kHz (Floeter et al. 1998), 20 Hz to 5 kHz
Stimulation. Ring electrodes are used to stimulate digital nerves, and surface electrodes to stimulate other sensory nerves. During maximal voluntary contraction, stimuli of
increasing intensities are delivered on sensory nerve fibers until a complete silent period of reproducible latency and duration is obtained. The stimulus intensity needs to be above pain threshold (Uncini et al. 1991; Shefner and Logigian 1993a). A stimulus duration of 0.2-0.5 ms is typically used in order to better activate sensory fibers (Kranz and von der Heydt 1973; Ongerboer and Goor 1976; Leis et al. 1991, 2000; Uncini et al. 1991; Pullman et al. 1996; Inghilleri et al. 1997; Manconi et al. 1998; Floeter et al. 1998; Syed et al. 2000; Stetkarova et al. 2001; Kofler et al. 2003a,b).
Different stimulus intensities were applied: 10x the stimulus threshold (ST) (Uncini et al.1991; Aurora et al. 1996, 1998; Leis et al. 2000), 10-20xST (Pullman et al. 1996), 10-13xST (Manconi et al. 1998; Rossi et al. 2000; Syed et al. 2000), 15xST
(Stetkarova et al. 2001). Other investigators used low and high stimulus intensities. Serrao et al. (2001) distinguished the pain stimuli into “mildly painful” ranging between 3-5xST, and “strongly painful” between 8-12xST. Rossi et al. (2003) evoked the CuSP both at low-intensities 2xST and high-low-intensities 8xST. When stimulating the digital nerves, for example Uncini et al. (1991) applied up to 32 mA, Inghilleri et al. (1997) 7-80 mA. Onset latency, duration and endpoint of the CuSP. The onset latency, duration and endpoint of the CuSP were identified in different ways. Some researchers measured latencies from the stimulus artefact (Pullman et al. 1996; Manconi et al. 1998). Some investigators identified the onset latency by visual inspection, as the clearly evident
beginning of an abrupt decrease of the mean rectified EMG activity, and the CuSP endpoint similarly, as a clearly evident abrupt resumption in EMG activity; the duration was
calculated from onset to endpoint (Rossi et al. 2000; Stetkarova et al. 2001; Kofler et al. 2003). For other investigators, the onset of the CuSP was defined as the time when EMG activity fell below 50% of the mean EMG activity amplitude, and the end as the time at which EMG activity returned to more than 50% of the mean EMG activity amplitude, and the duration as the interval between these measures (Pullman et al. 1996; Manconi et al. 1998; Syed et al. 2000; Serrao et al. 2001; Rossi et al. 2003). Others required 80% instead of 50% of the mean EMG activity amplitude (Inghilleri et al. 1997, 2002; Kofler 2003; Kofler et al. 2004).
Some investigators analyzed 250 ms before and after the stimulus for their CuSP studies (Pullman et al. 1996). Most investigators measured the CuSP from the averaged values of 10 trials (Inghilleri et al. 1997; Aurora et al. 1998; Syed et al. 2000, Serrao et al. 2001; Rossi et al. 2003).
Recording and stimulation sites. The CuSP was studied from different muscles, and in response to the stimulation of various sensory nerves.
Most recordings of the CuSP were performed from hands. Very often recording was from abductor pollicis brevis (APB) with digit II stimulation (Cacia et al. 1973; Shahani and Young 1973; Leis et al. 1992, 2000; Aurora et al. 1996, 1998; Floeter et al. 1998; Serrao et al. 2001; Stetkarova et al. 2001). The CuSP was also recorded from first dorsal interosseus, extensor digitorum indicis, and flexor digitorum profundus muscles after stimulating the fingers (Kranz and von der Heydt 1973). Stephens and Usherwood (1976) recorded the CuSP from first dorsal interosseus with stimulation of digits II and V. The CuSP was studied from opponens pollicis muscle with digit II stimulation (Pullman et al. 1996; Rossi et al. 2000), from APB muscle with digit V stimulation (Leiss et al. 1992, 1995; Manconi et al. 1998; Syed et al. 2000), from abductor digiti minimi (ADM) muscle with digit V stimulation (Kofler 2003). It was recorded from extensor carpi, flexor carpi, triceps brachii, biceps brachii, deltoid with digit II or V stimulation (Floeter et al. 1998; Leis et al. 2000; Serrao et al. 2001).
Some authors investigated the dermatomes (Inghilleri et al. 1997; Polidori et al. 1997; Kofler et al. 2003). For example Inghilleri et al. (1997) studied the CuSP by stimulating the C8 dermatome with digits IV-V, C7 dermatome with digits II-III, and C5 dermatome with surface electrodes placed on the lateral aspect of the arm, and recorded from ipsilateral first dorsal interosseus, ADM, extensor carpi et flexor carpi ulnaris, triceps brachii, biceps brachii.
In the legs the CuSP was recorded from tibialis anterior muscle with sural nerve stimulation (Shahani and Young 1973; Logigian and Shahani 1986; Uncini et al. 1991; Logigian et al. 1999; Rossi et al. 2000; Syed et al. 2000), and from soleus or gastrocnemius muscles with sural nerve stimulation (Shahani and Young 1973; Logigian and Shahani 1986; Uncini et al. 1991; Shefner and Logigian 1993).
4.3. Results
A set of normal values from larger populations is not available for the CuSP. The values available for the limbs are summarized in tables 2 and 3.
In all studies stimulus to obtain a CuSP required to be painful (Uncini et al. 1991; Shefner and Logigian 1993a).
With increasing stimulus intensity CuSP onset latency decreases and duration increases (Uncini et al. 1991; Shefner and Logigian 1993a; Leis et al. 2000); it then
plateaus and becomes reproducible (Caccia et al. 1973; Serrao et al. 2001), although with slight variations from trial to trial. Stimulation of fingers evokes a large CuSP with no conspicuous difference between stimuli applied to the C6 (digit II) to C8 (digit V) dermatomes, whereas proximal stimulation of the C5 dermatome induced no CuSP even with very strong and painful stimuli (Inghilleri et al. 1997).
The CuSP varies with the site of recording. Onset latency is substantially shorter in proximal muscles, consistent with a shorter reflex pathway (Uncini et al. 1991; Leis et al. 1992; Floeter et al. 1998; Stetkarova et al. 2001; Kofler 2003). The inhibitory response decreases from distal to proximal muscles, as shown by the decreased CuSP duration (Inghilleri et al. 1997; Polidori et al. 1997). The CuSP of the biceps and deltoid muscles is of very short duration or not obtainable (Inghilleri et al. 1997; Leis et al. 2000).
A CuSP was always recorded from the muscles of a limb when stimuli were applied on any distal sensory nerve of the same limb. However, with a degree of inhibition that varied. Kofler (2003) observed that CuSP was more pronounced in APB when
stimulating digit II than digit V.
CuSP latency recorded from small hand muscles is approximately 75 ms. Kofler and Poustka (2004) found that the latency of CuSP is similar on right and left limbs with no significant influence of handedness. Gender differences relate to the height of the subjects, with shorter CuSP onset latencies in women (Kofler and Poustka 2004). The latency of the CuSP varies from trace to trace (Uncini et al. 1991; Floeter et al. 1998).
Kofler and Poustka (2004) found, that the duration of CuSP does not differ on right and left limbs. CuSP duration decreases with increasing contraction strength (Uncini
Table 2. Cutaneous silent period in upper limb (results of other investigators) Mean Recording site Stimulation site Latency (SD) ms Duration (SD) ms Subjects N Authors APB digit II 71-92 74.7 (8.1) 80 70.5 (6.9) 72.3 (9.8) 74.8 (7.0) 43 (5) 31-66 44.9 (10.6) 30-50 55 (8.2) 58.1 (15.8) 33 (4.2) 87 (15) 5 15 6 5 9 12 20 Leis et al. 1992 Kaneko et al. 1997 Floeter al. 1998 Corsi et al. 2002 Stetkarova et al. 2001 Rossi et al. 2003 Kofler 2003
ADM digit II 57 (7) 56 (18) 20 Kofler 2003
APB digit V 72 (11) 58 (8) 59.4 (9.6) 69 (10) 12 20 Syed et al. 2000 Kofler 2003
ADM digit V 49 (2) 68 (14) 20 Kofler 2003
FDI digit II 46 (5) 81 (18) 20 Kofler 2003 FDI digit V 69.4 (4.34) 52 (3) 46.7 (6.79) 83 (14) 7 20 Inghilleri et al. 2002 Kofler 2003
OP digit II 69.8 (4.9) 37.3 (9.1) 8 Uncini et al. 1991 APB = abductor pollicis brevis; ADM = abductor digiti minimi; FDI = first dorsal interosseous; OP = opponens pollicis.
Table 3. Cutaneous silent period in lower limb (results of other investigators)
Mean
Recording Stimulation Subjects Authors
site site Latency (SD) Duration (SD) N
ms ms
Soleus suralis 90-100 40-50 2 Logigian et al.
1986
85-100 - 6 Shefner and
Logigian 1993
Gastrocnemius suralis 93.7 (10.8) 47 (11.4) 8 Uncini et al. 1991
TA suralis 97 (13) - 12 Syed et al. 2000
TA = tibialis anterior; - = not provided.
et al. 1991; Shefner and Logigian 1996; Serrao et al. 2001).
Uncini et al. (1991) found that a CuSP could always be obtained following contralateral limb stimulation, with an onset latency which was similar to the silent period onset from ipsilateral stimulation. Leis et al. (2000) could record a CuSP of short duration on thenar muscle following contralateral digit II stimulation in 1 of 5 subjects, whereas Kofler and Poustka (2005) recorded no CuSP in a similar experiment performed on 15 subjects.
4.4. CuSP clinical application
The CuSP has been studied in a number of pathological conditions in order to assess conduction of the peripheral and central pathways of this response in patients (Floeter 2003).
4.4.1 CuSP in disorders of the peripheral nervous system
CuSP was studied in patients with various sensory neuropathies. Uncini et al. (1991) studied 2 patients with Friedreich’s ataxia and a patient with chronic idiopathic ataxic neuropathy. All patients had absent deep tendon reflexes, loss of proprioceptive and vibration sense but preserved pain sensation. Although standard neurography of large sensory fibers disclosed no response, a CuSP was obtained in all patients. Later Serrao et al. (2001) studied the CuSP in 4 patients with Friedreich’s ataxia. They found that in these patients stronger stimuli were required to obtain a CuSP than in healthy subjects. Leis et al. (1992) studied a patient with a pure sensory neuropathy causing absent sensory nerve action potentials, and recorded a normal CuSP from APB with digit II and V stimulation. Later Leis (1994) reported a patient presenting with a similar situation in whom the CuSP (recorded in the same manner) had a markedly prolonged latency. He concluded that CuSP studies are able to identify conduction abnormalities not detected by routine studies. The CuSP was recorded in 3 patients with abetalipoproteinemia and a sensory neuropathy leading to areflexia and ataxia by Sandbrink et al. (1999). Sensory nerve action potentials were of low amplitude or absent, but CuSP was normal showing that patients with
abetalipoproteinemia have a severe large fiber sensory neuropathy but intact small fibers. The CuSP was investigated in 24 patients with Fabry′s disease by Syed et al. (2000). In this X-linked lysosomal storage disorder caused by a deficiency in alpha-galactosidase A, nerve biopsy shows loss of small myelinated fibers and autopsy loss of small diameter ganglion cells. As the disease progresses, patients develop abnormalities of large diameter fibers, thought to be secondary to dysfunction of other organs, such as the kidney. They found normal CuSP in the upper extremity, but CuSP of either reduced or increased duration in
the lower extremity. Patients with CuSP of reduced duration had a slightly elevated
vibration threshold and sensory potentials of reduced size. These authors concluded that the CuSP is relatively insensitive to measure small fiber dysfunction in case of mild and
moderate impairments. They further suggested that large diameter fibers may contribute to CuSP production. Corsi et al. (2002) studied 2 patients with hereditary sensory autonomic neuropathy, a rare disease with sensory and autonomic dysfunction caused by incomplete development of sensory and autonomic neurons. In these patients CuSP was absent when stimulation concerned one digit but a CuSP of reduced duration could be obtained when stimuli were applied to two digits. Osio et al. (2004) assessed the CuSP in 26 HIV-positive patients with polyneuropathy. They showed a significant increase of the latency of the CuSP in all patients.
CuSP was studied in entrapment neuropathies. CuSP studies have been performed in CTS by Aurora et al. (1998), by Kofler et al. (2003b) and by our group (Svilpauskaite et al. 2006a). Aurora et al. (1998) studied CuSP recorded from thenar muscles with digits II and V stimulation during maximal sustained thumb abduction in 19 patients with CTS. In the 17 patients with mild and moderate CTS the CuSP to digit II stimulation had a prolonged duration. In the 2 patients with severe CTS the CuSP was absent. This may have been caused by the atrophy of APB. Kofler et al. (2003b)
investigated 4 patients with severe entrapment neuropathies (2 CTS and 2 ulnar neuropathy at the elbow). In all, despite that sensory nerve action potentials were absent in the affected nerves a CuSP was always obtained. They concluded that A delta fibers were preserved across the lesion sites. The results obtained in CTS by our group will be given further on (cf. p. 52).
The CuSP was studied in 21 patients with meralgia paresthetica from the vastus medialis muscle following stimulation of the lateral femoral cutaneous nerve by Tataroglu et al. (2005). A CuSP of prolonged latency and reduced duration was observed in all patients along with conduction abnormalities of the lateral femoral cutaneous nerve.
4.4.2. CuSP in disorders of the central nervous system
The CuSP has been studied in a variety of disorders of the central nervous system. The CuSP was recorded in Parkinson’s disease and in dystonic patients
(Nakashima and Takahashi 1992; Pullman et al. 1996; Serrao et al. 2002). In 14 patients with Parkinson’s disease studied by Nakashima and Takahashi (1992) latency and duration of CuSP (thenar – digit II) were within normal limits. In contrast, Pullman et al. (1996) reported prolonged duration of the CuSP in hand muscles bilaterally in 7 patients with Parkinson’s disease, and in 11 patients with primary brachial dystonia. The latency of the CuSP was not different between patients and controls. They concluded that the abnormally prolonged durations may reflect dysfunctional basal ganglia timing influences over spinal circuitry. Serrao et al. (2002) also found a prolonged duration of the CuSP in 14 patients with idiopathic Parkinson’s disease and in 13 patients with other forms of Parkinsonism. They showed that the improvement of the rigidity and bradykinesia with L-Dopa resulted in a shortening of the CuSP duration in patients with idiopathic Parkinson’s disease.
The CuSP has been studied in 4 syringomyelia patients by Stetkarova et al. (2001). In syringomyelia, in which pain and thermal sensations are impaired. CuSP was absent or shortened on the affected side and normal on the unaffected side in all 4 patients. The authors concluded that CuSP, generated at the spinal level by the small myelinated A delta fibers, can be used to assess pain sensation in the early stage of syringomyelia, in which abnormality may relate to direct disruption of the posterior horn of the spinal cord. Kaneko et al. (1997) reported similar findings in 5 additional syringomyelia patients.
Kofler et al. (2003a) recorded the CuSP of 9 patients with intramedullary spinal cord lesions of different etiologies causing hypalgesia, hypothermesthesia, or pain in at least one upper extremity. They found that in all patients with cervical lesions CuSP was absent or of reduced duration, but that it was normal in a patient in whom the lesion
concerned the thoracic medulla. They concluded that upper extremity CuSP is sensitive for the assessment of cervical intramedullary lesion, and that abnormal CuSP is highly
5. SUBJECTS AND METHODS OF STUDY
5.1. Subjects
We studied healthy controls and patients with CTS and PNP. These controls and patients were examined in the electroneuromyography laboratories of the Neurology Departments of KMUK and Geneva University Hospital.
The control group (N=50) consisted in 36 women (72%) and 14 men (28%), with no neurological disorders and normal nerve conduction studies (Fig. 2). Their mean age was 43.2 years (standard deviation (SD) 12.8; range 18 to 66 years). Their mean height was 169.8 cm (SD 8.3 cm; range 150 to 192 cm); their mean weight was 73.2 kg (SD 14.3 kg; range 45 to 115 kg); their index of body mass was 25.4 kg/m2 (SD 4.4 kg/m2; range 18
to 38.1 kg/m2) (Fig. 3). These subjects were right-handed (N=42) and left-handed (N=8).
SUBJECTS SEX 36 68 59 14 12 81 0 20 40 60 80 100 controls CTS PNP No Female Male
FIGURE 2. Gender of the controls and of patients with carpal tunnel syndrome (CTS) and polyneuropathy (PNP).
Patients distribution by age controls CTS PNP N=50 N=80 N=140 10 20 30 40 50 60 70 80 90 age, y ear _________________n.s. n.s. ______________________________
Patients distribution by height
controls CTS PNP N=50 N=80 N=140 150 155 160 165 170 175 180 185 190 195 hei gh t, c m _______________________________ _______________n.s. n.s.
Patients distribution by w eight
controls CTS PNP N=50 N=80 N=140 40 50 60 70 80 90 100 110 w e ight , k g ___________________________________ ________________n.s. n.s.
Patients distribution by index of body m ass
controls CTS PNP N=50 N=80 N=140 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 B M I, k g /m 2 Mean ±SD ±1,96*SD ________________ __________________________________n.s. n.s.
FIGURE 3. Age, height, weight and body mass index (BMI) of healthy controls and of patients with carpal tunnel syndrome (CTS) and polyneuropathy (PNP).
The right side was investigated first. The subjects lied supine in a comfortable position throughout the study.
The CTS patients group (N=80) consisted in 68 women (85%) and 12 men (15%) (Fig. 2). Their mean age was 52.1 years (SD 11.7 years; range 23 to 76 years). Their mean height was 165.6 cm (SD 6.7 cm; range 150 to 182 cm); their mean weight was 75.8 kg (SD 12.3 kg; range 52 to 120 kg); their index of body mass was 27.7 kg/m2 (SD 4.3 kg/m2; range 18.8 to 38.5 kg/m2) (Fig. 3). CTS hands were divided into three groups based on conduction studies indicative of a myelinic dysfunction in “mild CTS”, of an additional moderate axonal lesion in “moderate CTS”, and of severe axonal lesion in “severe CTS”.
- Mild CTS: slowing of median nerve sensory conduction (on II or III digit) within the
carpal tunnel as compared to that of the ulnar nerve (on V digit) without conspicuous reduction of the size of the evoked potential, with either normal (< 3.6 ms) or prolonged median distal motor latency, up to 4.2 ms.
- Moderate CTS: reduced conduction velocity and size of median nerve sensory evoked
potential (on digit II or III) as compared to that of the ulnar nerve (on digit V), and prolonged motor distal latency more than 4.2 ms, reduced median CMAP amplitude (between 5.0 and 2.5 mV).
- Severe CTS: severe reduction in size or absent response of median sensory nerve, and
reduced CMAP amplitude (≤ 2.5 mV) or absent response.
No CTS patient had a complete loss of sensation within the territory of the median nerve on their CTS hand.
The PNP patients group (N=140) consisted in 59 women (42%) and 81 men (58%) (Fig. 2). Their mean age was 49 years (SD 18.1 years; ranged from 18 to 83 years). Their mean height was 172 cm (SD 8.7 cm; range 147 to 190 cm); their mean weight was 73.9 kg (SD 14.3 kg; range 43 to 115 kg); their index of body mass was 25 kg/m2 (SD 4.7 kg/m2; range 14.1 to 46.0 kg/m2) (Fig. 3). Patients with PNP were divided into three groups based on conduction studies indicative of a myelinic dysfunction in “myelinic PNP”, of an axonal lesion in “axonal PNP”, and of mixed lesion in “axono-myelinic PNP”.
The Kaunas Regional Committee of Biomedical Ethics approved the method of the study (Protocol N. BE-2-26). All subjects gave informed consent.
5.2. Methods
The subjects were laid supine in a comfortable position. Neurological examination, nerve conduction studies were performed on all controls and patients. The gender, age, height and weight were recorded. Skin temperature was measured on hand and ankle during nerve conduction studies.
Neurophysiological investigation was performed on standard electrodiagnostic equipments (Mystro MS 20, Medelec, Old Woking, Surrey, UK; Viking NT, Nicolet, Madison Wisconsin, USA).
Sensory nerve conduction studies were performed using ring electrodes to record antidromic sensory action potentials of median nerve on digit II, and of ulnar nerve on digit V (annexes 1, 2). Ring electrodes were placed around the proximal and middle phalanx. Stimuli were given at the wrist and palm levels. Surface electrodes were used to record antidromic sensory action potential of radial nerve with stimulation on the ridge of the radius 100 mm from the recording electrodes, of sural and superficial peroneal nerves with stimulation on the calf (annexes 3, 4, 5).
For motor nerve conduction studies, surface recording electrodes were used to perform standard muscle belly - tendon recordings. At the upper limbs, we studied the median and ulnar nerves. The median nerve was stimulated at the wrist using a normalized 55 mm distance from the cathode to the active recording electrode placed on APB and at the elbow (annex 6). The ulnar nerve was stimulated at the wrist and elbow with recordings from thenar muscles and ADM (annex 7). Stimuli to ADM also used a normalized distance of 55 mm to the active recording electrode. At the lower limbs, we studied the peroneal and tibial nerves. The peroneal nerve was stimulated on the anterior aspect of the ankle and over the nerve in front and behind the neck of the fibula with recording from extensor digitorum brevis and/or tibialis anterior muscles (annex 8). The tibial nerve was stimulated at the ankle, then at the knee with recording from abductor hallucis muscle (annex 9). F-wave studies were performed for all nerves.
For CuSP studies, the electrodes used for sensory recordings were used to stimulate digit II and digit V, the radial nerve on the radial aspect of the wrist, the sural
nerve behind the lateral malleolus and the superficial peroneal nerve medial to the lateral malleolus at the ankle. Ring electrodes were around the proximal and middle phalanx to stimulate digit II, and around the middle and distal phalanx to stimulate digit V. Recordings were performed using surface electrodes attached in a belly-tendon fashion (Fig. 4). At the upper limbs, we recorded from APB, ADM, flexor digitorum superficialis, flexor carpi ulnaris, extensor digitorum communis, biceps brachii and triceps brachii muscles. At the lower limbs, we recorded from extensor digitorum brevis, abductor hallucis, tibialis
anterior and soleus. Maximum voluntary contraction was assessed by audiovisual feedback. Amplifier filters were set between 2 Hz and 10 kHz. Oscilloscope sweep time was 20 ms/div for upper limbs and 50 ms/div for lower limbs. Sensitivity was 0.5 mV to 2 mV/div depending on the amplitude of voluntary activity.
During maximal voluntary contraction, single stimuli of increasing intensities and 0.3 ms duration (best duration for single pulse stimuli as determined during a pilot study done on 4 subjects) were delivered on digits II, V, on the radial, sural, and superficial peroneal nerves, until a complete silent period of reproducible latency and duration was obtained. When this could not be achieved, stimulus duration was increased in steps of 0.1 ms, up to 1.0 ms. CuSP was recorded on the upper limb from APB and ADM with both digit II and V stimulation; flexor digitorum superficialis and biceps brachii with digit II stimulation; extensor digitorum communis and triceps brachii with radial nerve stimulation; flexor carpi ulnaris with digit V stimulation. On the lower limb, CuSP was recorded from extensor digitorum brevis, tibialis anterior, abductor hallucis and soleus with sural and superficial peroneal nerves stimulation. Attempts were made to record: from one upper limb (APB and ADM) when stimuli were applied the contralateral upper limb (digit II and V); from one lower limb (tibialis anterior) when stimuli concerned the upper limb on the same side (digit II) and the contralateral lower limb (suralis). The onset and endpoint latencies of the CuSP were identified by visual inspection as the beginning of an abrupt decrease and recovery of the EMG activity (Fig. 1).
In the control group we performed sensory nerve conduction studies, and CuSPs at all levels. In the CTS patient groups we performed sensory (median, ulnar, radial) and motor (median, ulnar) nerves conduction studies, and CuSP was recorded from thenar (digit II stimulation), ADM (digit II and V stimulation), flexor digitorum superficialis (digit
FIGURE 4. For cutaneous silent period studies, ring electrodes (S) were used to stimulate digit II. Ring electrodes were around the proximal and middle phalanx. Recordings were performed using surface electrodes (R) attached in a belly-tendon fashion on abductor pollicis brevis muscle. The ground electrode (G) is on the dorsum part of the hand between stimulating and recording electrodes.
II stimulation), extensor digitorum communis (n. radialis superficialis stimulation) (Fig. 4; annexes 10-13). In the PNP patient groups we performed sensory and motor nerves
conduction studies on the upper and lower limbs, and CuSP was recorded from APB (digit II stimulation), ADM (digit V stimulation), tibialis anterior (superficial peroneal nerve stimulation) (Fig. 4; annexes 11, 14).
5.3. Statistical analysis
Statistical analysis was performed using the software SPSS (Statistical Package for Social Science) for Windows Version 12.0 (Apache Software Foundation, Chicago, Illinois, USA) and Statistica 7.0 (Stat Soft Inc, Tulsa, USA).
As CuSP latency and duration vary slightly from one recording to the other, CuSP latency and duration were established as the mean values obtained from 4 recordings. For each CuSP parameter, we calculated the mean, SD, minimal and maximal values.
Data were analyzed by descriptive statistics with frequency distribution and crosstabs calculation. Student’s t criterion was used for comparison of means. Using this criterion is possible when sample variables are distributed normally. Kolmagorov-Smirnov goodness-of-fit test was performed in order to assess the normality of distribution.
Correlation analysis was performed using Pearson coefficient (r) of rank correlation. Correlation coefficients lay within the range -1 to +1, with “zero” midpoint indicating no linear association between the two variables. When r is from -0.3 to 0 or from 0 to +0.3, the correlation between the two variables is very small. When r is from 0.3 to -0.5 or from +0.3 to +-0.5, the correlation is small; when r is from --0.5 to -0.7 or from +-0.5 to +0.7, the correlation is moderate; when r is from -0.7 to -0.9 or from +0.7 to +0.9, the correlation is strong; when r is from -0.9 to -1.0 or from +0.9 to +1.0, the correlation is very strong.
ANOVA (one way analysis of variance) was used to compare CuSP
parameters between patient groups and controls. Data were analyzed using a Bonferroni correction and LSD (least significant difference).
The hypotheses were considered statistically “significant” at the level of p<0.05, “very significant” at the level of p<0.01. The hypotheses were considered statistically “not significant” at the level of p>0.05.
RESULTS OF THE STUDY
6.1. CuSP in normal controls
CuSP results are provided in tables 2 to 15. Results obtained by other investigators are provided for comparison in tables 2 (upper limbs) and 3 (lower limbs), whereas our own results are given in table 4. Our results have been used in part in previous articles (Svilpauskaite et al. 2006a,b).
The study was performed on both sides in 47 subjects and on one side in 3 subjects. Hence, the results include 97 sides.
CuSP latency showed a tendency to increase with increasing height, age and weight (Tables 5, 6, 7). This relation was statistically significant between groups only for height when it was more than 180 cm (p<0.01). The tendency of the latency to increase with weight can be explained by the mean higher height and older age of heavier subjects (Table 8). CuSP latencies were similar on right and left limbs (not statistically different) (Tables 9, 10; Fig. 5). CuSP latencies were shorter in women than in men (Tables 11, 12; Fig. 5). However, this is explained by their smaller height.
CuSP duration did not differ significantly in relation with gender, side, height, age and weight (Tables 9-15; Fig. 5).
6.1.1. Effect of stimulus intensity on CuSP
In all subjects, electrical stimuli to sensory nerves had to be painful to yield a CuSP. The CuSP to biceps brachialis that required very intense stimuli was tested in 28 subjects only, hence on 56 sides. A CuSP of short duration began to be visible starting with stimulation intensities between 50-100 V at the upper limb; higher intensities, around
Table 4. Cutaneous silent period in limbs of healthy controls (N = 50 subjects, 97 sides; for recordings in biceps brachii muscle, N = 28 subjects, 56 sides)
Recording site Stimulation site Mean latency (SD) Mean duration (SD)
ms ms APB digit II 74.9 (5.8) 43.9 (7.8) digit V 76.0 (5.6) 38.4 (5.8) digit V 75.4 (5.6) 39.8 (7.5) ADM digit II 75.1 (7.7) 36.8 (7.2) radialis 67.4 (6.1) 38.3 (8.1) EDC radialis 66.1 (5.8) 36.3 (6.0) digit II 71.2 (6.6) 34.7 (6.1) FDS digit II 70.4 (6.3) 36.3 (6.0) FCU digit V 70.6 (6.0) 37.4 (5.2) Triceps radialis 63.6 (5.1) 33.4 (5.3) BB digit II 73.3 (4.6) 24.6 (7.3) suralis 101.6 (9.9) 52.1 (12.1) AH peroneus superficialis 101.0 (12.8) 54.7 (12.4) EDB peroneus superficialis 100.2 (10.4) 47.7 (10.1) suralis 100.0 (8.7) 45.8 (10.6) Soleus peroneus superficialis 99.9 (10.9) 45.2 (10.7) peroneus TA superficialis 98.9 (6.5) 42.1 (9.6) suralis 102.3 (8.8) 45.2 (8.5)
APB = abductor pollicis brevis; ADM = abductor digiti minimi; EDC = extensor digitorum communis; FDS = flexor digitorum superficialis; FCU = flexor carpi ulnaris; BB = biceps brachii; AH = abductor hallucis; EDB = extensor digitorum brevis; TA = tibialis anterior.
Table 5. Cutaneous silent period mean latency in limbs of healthy controls in relation to height (N = 50 subjects, 97 sides)
Height (cm)
Recording Stimulation ≤160 161-170 171-180 >180 site site (13 sides) (44 sides) (28 sides) (12 sides)
Mean latency (SD), ms APB digit II 73.2 (5.3) 73.7 (5.3) 75.6 (4.5) 80.1 (5.9) digit V 74.7 (4.5) 74.9 (5.0) 75.1 (4.8) 82.3 (7.0) ADM digit V 73.7 (3.9) 73.8 (3.6) 75.6 (5.7) 82.9 (7.3) digit II 73.9 (6.7) 72.6 (5.3) 75.6 (8.4) 83.9 (8.4) EDC radialis 65.7 (4.2) 64.5 (4.7) 65.8 (4.8) 72.7 (8.6) FDS digit II 68.7 (4.5) 68.9 (5.9) 71.4 (7.1) 74.9 (6.7) Triceps radialis 60.9 (4.7) 63.1 (3.5) 63.3 (5.6) 69.5 (6.7) suralis 98.6 (5.2) 100.1 (8.0) 101.9 (12.2) 109.7 (10.8) AH peroneus superficialis 92.6 (7.5) 100.9 (7.6) 101.4 (16.5) 109.4 (17.5) EDB superficialis peroneus 99.2 (4.3) 97.8 (9.6) 100.2 (7.1) 110.3 (17.8) suralis 96.5 (4.3) 97.6 (6.5) 100.3 (6.9) 111.9 (12.7) Soleus peroneus superficialis 92.3 (6.3) 98.2 (8.1) 101.0 (11.5) 111.7 (13.5) TA peroneus superficialis 93.1 (5.4) 100.2 (5.2) 98.0 (6.7) 101.5 (7.7) suralis 94.3 (4.7) 101.1 (6.7) 103.4 (8.8) 112.0 (10.5)
APB = abductor pollicis brevis; ADM = abductor digiti minimi; EDC = extensor digitorum communis; FDS = flexor digitorum superficialis; AH = abductor hallucis; EDB = extensor digitorum brevis; TA = tibialis anterior. CuSP latency was longer in subjects which height was more then 180 cm (p<0.01).
Table 6. Cutaneous silent period mean latency in limbs of healthy controls in relation to age (N = 50 subjects, 97 sides)
Age (years)
Recording Stimulation ≤30 31-40 41-50 51-60 >60 site site (18 sides) (22 sides) (26 sides) (19 sides) (12 sides)
Mean latency (SD), ms APB digit II 74.1 (5.5) 73.9 (5.3) 76.1 (6.1) 74.0 (6.5) 76.7 (4.7) digit V 73.2 (4.0) 74.5 (5.9) 78.2 (5.5) 75.5 (4.9) 78.5 (6.4) ADM digit V 74.8 (4.4) 75.5 (5.1) 76.2 (6.0) 72.4 (5.4) 79.2 (7.9) digit II 75.8 (7.9) 73.9 (6.0) 74.9 (8.2) 75.0 (7.4) 78.0 (7.5) EDC radialis 64.0 (4.6) 65.3 (5.4) 67.7 (7.4) 65.1 (6.8) 69.2 (5.2) Triceps radialis 61.5 (5.0) 62.7 (4.6) 63.6 (4.9) 64.3 (5.8) 67.6 (5.4) AH suralis 103.3 (12.3) 101.2 (9.4) 99.5 (9.8) 104.1 (9.4) 102.1 (6.7) peroneus superficialis 94.7 (7.2) 98.2 (15.7) 102.7 (12.9) 108.6 (13.8) 101.5 (8.2) EDB peroneus superficialis 94.9 (5.8) 101.5 (6.4) 98.7 (13.9) 106.4 (8.6) 100.2 (6.8) Soleus suralis 97.3 (8.0) 97.3 (7.4) 101.1 (10.7) 104.3 (8.4) 99.9 (8.1) TA suralis 97.6 (6.6) 98.9 (6.0) 105.5 (9.8) 106.1 (9.4) 102.4 (6.6) APB = abductor pollicis brevis; ADM = abductor digiti minimi; EDC = extensor digitorum communis; AH = abductor hallucis; EDB = extensor digitorum brevis; TA = tibialis
Table 7. Cutaneous silent period mean latency in limbs of healthy controls in relation to weight (N = 50 subjects, 97 sides)
Weight (kg)
Recording Stimulation ≤60 61-70 71-80 81-90 >90 site site (19 sides) (26 sides) (25 sides) (19 sides) (8 sides)
Mean latency (SD), ms APB digit II 71.0 (4.2) 74.2 (4.8) 76.3 (4.1) 77.1 (7.2) 77.0 (4.3) digit V 73.9 (4.9) 74.3 (5.4) 77.2 (6.3) 78.8 (5.4) 76.3 (3.3) ADM digit V 73.0 (5.5) 74.8 (4.9) 76.8 (5.8) 77.2 (6.6) 74.5 (6.6) digit II 73.2 (6.2) 73.6 (5.1) 76.1 (8.8) 79.1 (8.9) 73.7 (5.0) EDC radialis 64.6 (4.7) 64.1 (4.4) 67.2 (5.0) 68.3 (8.4) 67.2 (4.8) FDS digit II 68.0 (4.0) 67.7 (5.7) 70.4 (5.0) 75.3 (5.7) 72.7 (10.5) Triceps radialis 62.1 (5.2) 61.6 (4.9) 63.7 (4.9) 66.2 (4.9) 67.2 (7.7) AH suralis 101.6 (5.8) 101.0 (14.7) 101.6 (7.7) 100.3 (4.3) 106.3 (13.5) peroneus superficialis 97.8 (8.9) 97.4 (14.0) 99.5 (8.9) 108.9 (15.0) 103.7 (13.8) EDB peroneus superficialis 99.0 (6.8) 96.0 (11.0) 99.5 (12.0) 105.4 (12.0) 105.6 (11.2) Soleus suralis 96.8 (6.5) 97.6 (7.8) 99.2 (6.1) 104.2 (10.0) 105.0 (10.2) TA peroneus superficialis 96.4 (6.4) 98.8 (6.5) 98.1 (6.5) 100.7 (6.1) 102.2 (6.4) APB = abductor pollicis brevis; ADM = abductor digiti minimi; EDC = extensor digitorum communis; FDS = flexor digitorum superficialis; AH = abductor hallucis; EDB = extensor digitorum brevis; TA = tibialis anterior.
Table 8. Antropometric data of healthy subjects in relation with height, weight and age
Height
<160 161-170 171-180 >180
(13 sides) (44 sides) (28 sides) (12 sides)
mean height (SD), cm 157.1 (3.3) 166.4 (2.5) 173.9 (2.0) 185.3 (3.9) sides in women 13 42 15 sides in men 2 13 12 mean age (SD), years 43.9 (15.9) 46.4 (11.4) 38.1 (12.5) 43.8 (12.0) mean weight (SD), kg 60.2 (16.6) 71.7 (10.3) 75.8 (12.9) 88.8 (13) Weight <60 61-70 71-80 81-90 >90
(19 sides) (26 sides) (25 sides) (19 sides) (8 sides)
mean weight (SD), kg 54.5 (5.2) 67.2 (3.0) 75.0 (2.9) 85.5 (3.1) 104.0 (7.8) sides in women 19 20 18 9 4 sides in men 6 7 10 4 mean height (SD), kg 161.2 (5.6) 169.7 (4.4) 172.6 (7.7) 173.6 (9.2) 172.5 (9.5) mean age (SD), years 41.7 (13.1) 36.8 (11.7) 43.3 (11.1) 47.5 (12.7) 57.5 (5.0) Age <30 31-40 41-50 51-60 >60
(18 sides) (22 sides) (26 sides) (19 sides) (12 sides)
mean age (SD), years 26.0 (3.8) 35.2 (2.5) 44.3 (2.9) 55.6 (3.0) 63.7 91.6) sides in women 13 18 20 11 8 sides in men 5 4 6 8 4 mean height (SD), cm 170.1 (7.8) 169.8 (7.5) 170.1 (7.3) 168.5 (9.5) 170.5 (11.6) mean weight (SD), kg 65.4 (10.7) 66.4 (11.7) 75.8 (9.0) 81.7 (18.7) 81.3 (13.4)
Table 9. Cutaneous silent period in upper limb in relation to the side studied (N = 50 subjects, 97 sides; for recordings in biceps brachii muscle, N = 28 subjects, 56 sides)
Mean latency (SD) ms
Mean duration (SD) ms
Recording site Stimulation site
right side left side right side left side
APB digit II digit V 75.5 (6.0) 76.8 (5.7) 74.3 (5.5) 75.3 (5.6) 43.4 (8.1) 38.6 (5.4) 44.4 (7.6) 38.2 (6.2) ADM digit V digit II radialis 75.4 (5.5) 74.2 (7.7) 67.5 (6.1) 75.4 (5.7) 75.9 (7.6) 67.4 (6.3) 39.3 (7.9) 37.8 (7.1) 38.1 (6.9) 40.2 (7.2) 36.0 (7.3) 38.5 (9.3) EDC radialis digit II 65.7 (6.1) 71.4 (6.9) 66.4 (5.5) 71.0 (6.3) 36.7 (5.9) 34.4 (6.5) 35.9 (6.1) 35.1 (5.7) FDS digit II 70.4 (6.0) 70.3 (6.7) 35.4 (6.7) 35.2 (6.4) FCU digit V 70.4 (6.9) 70.9 (4.8) 36.5 (5.4) 38.4 (5.0) Triceps radialis 63.2 (4.5) 64.0 (5.7) 33.0 (5.0) 33.9 (5.5) BB digit II 73.7 (4.6) 72.8 (4.7) 24.3 (7.8) 24.9 (6.9) APB = abductor pollicis brevis; ADM = abductor digiti minimi; EDC = extensor digitorum communis; FDS = flexor digitorum superficialis; FCU = flexor carpi ulnaris; BB = biceps brachii. Cutaneous silent periods are not statistically different on right and left limbs (p>0.05).
Table 10. Cutaneous silent period in lower limb in relation to the side studied (N = 50 subjects; 97 sides) Mean latency (SD) ms Mean duration (SD) ms Recording site Stimulation site
right side left side right side left side AH suralis peroneus superficialis 100.9 (8.9) 100.6 (12.9) 102.3 (10.9) 101.3 (12.8) 52.8 (12.7) 54.5 (12.3) 51.4 (11.5) 54.9 (12.7) EDB peroneus superficialis 100.2 (10.7) 100.2 (10.3) 47.5 (9.4) 47.9 (10.8) Soleus suralis peroneus superficialis 99.1 (9.0) 99.6 (10.6) 100.8 (8.3) 100.2 (11.3) 45.2 (10.5) 46.6 (11.2) 46.3 (10.7) 44.0 (10.3) TA peroneus superficialis suralis 98.1 (7.1) 101.7 (9.3) 99.4 (5.9) 102.8 (8.4) 42.3 (9.5) 45.8 (9.2) 41.9 (9.7) 44.5 (7.8) AH = abductor hallucis; EDB = extensor digitorum brevis; TA = tibialis anterior. Cutaneous silent periods are not statistically different on right and left limbs (p>0.05).
A.
B.
Lat.R Lat.L Dur.R Dur.L 30 40 50 60 70 80 90 100 lat enc y , d ur at ion, m s n.s. n.s. __________________ _________________
Lat.F Lat.M Dur.F Dur.M 20 30 40 50 60 70 80 90 100 lat enc y , d ur at ion, m s Mean ±SD ±1,96*SD p<0.01 n.s. _____________________ ____________________ FIGURE 5. Cutaneous silent period latency and duration in 50 normal subjects: A. on right and left upper limbs; B. in women and men control subjects. Stimulation is on digit II. Recording is from abductor pollicis brevis (APB). Lat = latency; Dur = duration; R = right; L = left; M = man; F = women; n.s. = not statistically significant (p>0.05).
Table 11. Cutaneous silent period in upper limb of healthy controls in relation to sex (N = 50 subjects, 97 sides) Mean latency (SD) ms Mean duration (SD) ms Recording site Stimulation site Women (70 sides) Men (27 sides) Women (70 sides) Men (27 sides) APB digit II digit V 73.5 (5.3) 74.8 (4.9) 78.43 (5.4) 79.2 (6.6) 44.0 (7.9) 37.5 (6.1) 43.7 (7.7) 37.5 (5.6) ADM digit V digit II 73.7 (5.8) 72.3 (5.5) 79.9 (6.8) 82.2 (8.1) 40.2 (7.2) 36.8 (7.1) 38.6 (8.3) 37.0 (7.5) EDC radialis digit II 64.6 (4.1) 71.0 (6.3) 70.1 (7.6) 71.4 (6.9) 36.1 (5.5) 35.1 (5.7) 36.7 (7.2) 34.4 (6.5) FDS digit II 68.8 (5.4) 74.7 (6.7) 35.1 (6.3) 35.8 (6.9) Triceps radialis 61.8 (4.0) 68.6 (5.4) 34.5 (5.8) 34.0 (7.5) BB digit II 72.7 (4.4) 75.7 (5.3) 25.7 (6.2) 26.6 (10.6) APB = abductor pollicis brevis; ADM = abductor digiti minimi; EDC = extensor digitorum communis; FDS = flexor digitorum superficialis; BB = biceps brachii. Cutaneous silent period latency is shorter in women than in men (p>0.01); duration does not differ statistically in women and in men (p>0.05).
Table 12. Cutaneous silent period in lower limb of healthy controls in relation to gender (N = 50 subjects; 97 sides)
Mean latency (SD) ms Mean duration (SD) ms Recording site Stimulation site Women
(70 sides) (27 sides) Men (70 sides) Women (27 sides) Men
AH suralis peroneus superficialis 99.9 (8.5) 97.9 (9.0) 106.4 (11.8) 109.5 (17.2) 53.4 (11.1) 55.8 (12.4) 55.6 (11.5) 56.8 (11.3)
EDB superficialis peroneus 98.2 (8.2) 105.8 (13.6) 48.1 (9.6) 50.0 (10.4)
Soleus suralis peroneus superficialis 97.4 (6.5) 96.6 (8.1) 107.0 (9.9) 109.1 (12.4) 46.0 (11.4) 44.0 (10.3) 46.7 (7.7) 44.8 (11.1) TA peroneus superficialis suralis 101.0 (7.1) 99.5 (6.6) 98.0 (6.2) 109.9 (9.8) 43.3 (9.5) 45.2 (8.6) 44.1 (9.3) 45.0 (8.3) AH = abductor hallucis; EDB = extensor digitorum brevis; TA = tibialis anterior. Cutaneous silent period latency is shorter in women than in men (p>0.01); duration does not differ statistically in women and in men (p>0.05).
Table 13. Cutaneous silent period mean duration in limbs of healthy controls in relation to height (N = 50 subjects, 97 sides)
Height (cm)
Recording Stimulation ≤160 161-170 171-180 >180 site site (13 sides) (44 sides) (28 sides) (12 sides)
Mean duration (SD), ms APB digit II 44.2 (7.9) 44.5 (8.1) 43.4 (8.0) 42.3 (7.1) ADM digit V 41.3 (5.6) 40.5 (7.7) 38.6 (7.3) 38.0 (9.2) digit II 34.8 (5.8) 38.3 (7.7) 35.6 (6.7) 36.9 (7.8) EDC radialis 34.4 (5.6) 37.2 (5.8) 34.4 (6.7) 39.1 (5.2) FDS digit II 32.4 (5.1) 36.4 (6.5) 33.5 (6.2) 38.3 (6.9) Triceps radialis 30.7 (5.1) 33.5 (4.9) 34.4 (6.7) 33.8 (5.4) EDB superficialis peroneus 43.4 (5.6) 47.5 (10.8) 48.3 (11.5) 51.7 (10.4) Soleus suralis 39.7 (9.7) 47.8 (10.5) 44.9 (10.5) 46.5 (10.3) peroneus superficialis 40.6 (6.5) 46.5 (11.2) 46.5 (11.0) 43.3 (10.7) TA peroneus superficialis 38.7 (9.4) 40.8 (8.4) 44.8 (11.8) 44.6 (7.2) suralis 43.0 (5.4) 45.0 (8.0) 46.0 (10.8) 46.5 (7.1)
APB = abductor pollicis brevis; ADM = abductor digiti minimi; EDC = extensor digitorum communis; FDS = flexor digitorum superficialis; EDB = extensor digitorum brevis; TA = tibialis anterior.
Table 14. Cutaneous silent period mean duration in limbs of healthy controls in relation to age (N = 50 subjects, 97 sides)
Age (years)
Recording Stimulation ≤30 31-40 41-50 51-60 >60 site site (18 sides) (22 sides) (26 sides) (19 sides) (12 sides)
Mean duration (SD), ms APB digit II 42.7 (8.1) 42.6 (7.6) 43.8 (9.4) 45.3 (5.4) 47.6 (4.2) digit V 37.9 (5.8) 40.2 (7.8) 37.8 (5.0) 36.4 (3.3) 40.2 (5.5) ADM digit V 38.1 (6.5) 37.6 (7.2) 39.8 (8.1) 43.1 (7.4) 40.8 (6.1) digit II 34.7 (5.3) 36.0 (5.8) 37.5 (8.8) 38.8 (6.1) 35.4 (4.7) EDC radialis 36.6 (4.8) 34.7 (4.8) 36.8 (6.5) 36.1 (8.0) 37.9 (4.5) FDS digit II 33.8 (6.8) 33.3 (5.3) 37.2 (7.5) 36.8 (4.9) 34.4 (7.1) Triceps radialis 35.3 (6.9) 32.6 (4.2) 33.8 (5.6) 32.5 (4.0) 32.9 (5.2) AH suralis 53.7 (17.5) 46.8 (12.4) 54.0 (10.4) 53.7 (8.6) 52.3 (6.0) peroneus superficialis 59.1 (14.8) 47.8 (11.6) 58.2 (9.2) 55.7 (12.6) 49.9 (6.6) EDB superficialis peroneus 45.0 (14.0) 44.2 (8.7) 49.1 (9.7) 50.2 (6.2) 50.9 (5.9) Soleus suralis 43.9 (12.3) 44.1 (10.7) 50.1 (11.3) 44.1 (9.2) 44.7 (5.3) peroneus superficialis 47.3 (13.0) 45.7 (10.8) 45.8 (11.4) 43.7 (7.7) 43.1 (9.1) TA peroneus superficialis 44.1 (10.9) 40.2 (11.9) 41.5 (8.0) 40.6 (5.8) 46.2 (10.4) suralis 46.4 (8.5) 44.2 (9.2) 45.1 (8.1) 44.5 (8.8) 46.2 (8.8) APB = abductor pollicis brevis; ADM = abductor digiti minimi; EDC = extensor digitorum communis; FDS = flexor digitorum superficialis; AH = abductor hallucis; EDB = extensor digitorum brevis; TA = tibialis anterior.
Table 15. Cutaneous silent period mean duration in limbs of healthy controls in relation to weight (N = 50 subjects, 97 sides)
Weight (kg)
Recording Stimulation ≤60 61-70 71-80 81-90 >90 site site (19 sides) (26 sides) (25 sides) (19 sides) (8 sides)
Mean duration (SD), ms APB digit II 44.0 (6.8) 43.8 (9.6) 43.4 (6.9) 42.5 (8.0) 48.4 (5.7) digit V 41.2 (8.8) 42.7 (9.8) 38.2 (7.3) 37.8 (5.9) 38.3 (4.7) ADM digit V 41.7 (8.1) 40.0 (9.1) 39.1 (6.8) 38.6 (6.8) 42.1 (4.0) digit II 34.0 (5.8) 37.7 (9.1) 38.2 (6.6) 35.6 (5.3) 39.5 (8.0) EDC radialis 35.7 (5.9) 38.8 (7.5) 36.2 (5.1) 34.6 (7.9) 35.8 (5.7) FDS digit II 31.6 (5.3) 36.3 (7.3) 36.8 (5.8) 34.9 (7.2) 38.6 (4.3) Triceps radialis 32.6 (5.4) 34.7 (6.5) 33.8 (6.2) 33.6 (4.2) 31.3 (5.4) AH suralis 46.7 (11.1) 50.7 (15.2) 54.7 (11.0) 54.2 (9.3) 54.2 (8.3) peroneus superficialis 50.7 (12.3) 54.1 (15.9) 56.7 (12.8) 54.0 (10.7) 56.2 (7.1) EDB superficialis peroneus 45.7 (9.1) 44.7 (12.2) 50.8 (11.1) 48.4 (7.0) 51.5 (8.1) suralis 44.2 (10.4) 45.9 (15.4) 45.6 (8.4) 47.3 (7.6) 44.7 (11.0) Soleus peroneus superficialis 44.5 (11.2) 48.1 (12.8) 46.0 (10.7) 42.3 (9.7) 44.9 (8.2) TA peroneus superficialis 37.1 (8.2) 40.5 (11.2) 44.6 (10.1) 42.6 (9.4) 43.5 (8.3) suralis 44.8 (7.5) 44.5 (6.3) 46.0 (9.6) 44.0 (9.4) 46.0 (8.9) APB = abductor pollicis brevis; ADM = abductor digiti minimi; EDC = extensor digitorum communis; FDS = flexor digitorum superficialis; AH = abductor hallucis; EDB = extensor digitorum brevis; TA = tibialis anterior.
100-150 V were required at the lower limbs. Stimulation intensity required to obtain a CuSP varied also depending on whether distal or proximal muscles were recorded with higher, intensities required for proximal muscles. The CuSP latency and duration that varied slightly from one stimulus to the next became reproducible across individual traces when stimulus intensity reached 200-250 V (with 0.3 ms stimulus duration). When stimuli of lower intensity were used, CuSP latency was longer and more variable. With increasing intensity CuSP onset latency diminished, duration increased, and variability became less conspicuous. On distal muscles, the shortest latency and longest duration was usually reached with stimuli around 200-250 V. On proximal muscles higher voltages were required, up to 400 V. Considering this variability and the fact that high voltages stimuli are unpleasant, we did not attempt to characterize further the CuSP threshold values of our normal volunteers.
6.1.2. CuSP in different muscles on hands and feet
The CuSP parameters differed when recording from a distal or a proximal muscle (Table 4). CuSP latency and duration were longer in distal than in proximal muscles. In distal muscles, a CuSP of rather long duration was always readily obtained. In proximal muscles, a CuSP was difficult to record from the biceps brachii; it was of rather long latency and very short duration (as if the early part of the silent period was missing), or even not obtained on both sides of 7 normal subjects (Table 4). A CuSP was always easily obtained in all subjects on the triceps brachii; but its duration was short.
6.1.3. CuSP from same limb but different innervation
The CuSP latency was similar in APB and ADM with digits II and V stimulation (not statistically different; Table 4; Fig. 6). In the legs CuSP latency was similar on abductor hallucis, soleus and tibialis anterior after sural or superficial peroneal nerves stimulation.
