- Email: [email protected]
Deriving pediatric nerve conduction normal values in the very young (<3 years)
Clinical Neurophysiology 131 (2020) 177–182
Contents lists available at ScienceDirect
Clinical Neurophysiology journal homepage: www.elsevier.com/locate/clinph
Deriving pediatric nerve conduction normal values in the very young (<3 years) Joe F. Jabre a,⇑, Matthew C. Pitt b, Ralph Smith b a b
Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA Department of Clinical Neurophysiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom
a r t i c l e
i n f o
Article history: Accepted 10 November 2019 Available online 22 November 2019 Keywords: Pediatric normal values Sensory Motor Nerve conductions E-norms
h i g h l i g h t s Pediatric EMG is an essential part of the workup of children with neuromuscular disorders. The paucity of normal values in the <3 years old poses a limitation in the analysis of their tests. The e-norms method is a fast and efficient method to derive a lab’s own normal values.
a b s t r a c t Objective: This work describes our efforts to obtain nerve conduction studies normal values in a pediatric cohort between birth and 3 years of age using the extrapolated norms or e-norms method. Interpretation of these studies poses major challenges when no reliable normal values can be found in the literature. Methods: The e-norms method was used to derive a reference range of upper and lower extremity sensory and motor nerve conductions normal values from a pediatric cohort referred to an EMG Laboratory for nerve conduction studies. Results: E-norms were calculated for Median, Ulnar, Superficial Peroneal, Sural, and Medial Plantar sensory studies, and for Median, Ulnar, Peroneal, and Tibial motor studies. Conclusions: Pediatric electrodiagnostic testing is a very challenging undertaking. The ability to obtain and use normal values from the neurophysiologist’s own referral pool adds great value to their diagnostic work-up. Significance: EMG and nerve conduction studies can yield invaluable information in the diagnostic workup of young infants. Using the e-norms method improves on the analysis and interpretation of electrophysiological studies in this age group. Ó 2019 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.
1. Introduction The work-up of neuromuscular disorders in young children can be a daunting task. Sensory and motor nerve conductions can add valuable information to the diagnostic work-up of young children particularly in relationship to the investigation of peripheral neu-
Abbreviations: E-norms, Extrapolated norms; EMG, Electromyography; IRB, Institutional Review Board; S, Sensory; M, Motor; Lat, Latency; CV, Conduction Velocity; P-W, Palm-Wrist; Sup Per, Superficial Peroneal; Med Plant, Medial Plantar; APB, Abductor Pollicis Brevis; ADM, Abductor Digiti Minimi; EDB, Extensor Digitorum Brevis; AH, Abductor Hallucis. ⇑ Corresponding author at: 167 N Poinsettia Pl, Los Angeles, CA 90036, USA. E-mail address: [email protected] (J.F. Jabre).
ropathies and, if taken in conjunction with motor unit parameters and neuromuscular jitter measurements, in the whole range of neuromuscular diseases that occur in children. Even though some of these conditions are rare, most of these infants have symptoms from birth and an early diagnosis can add significant information to the choice of treatment given that some of these conditions can be associated with significant morbidity. Despite the progress in our ability to screen genetically for some disease entities, there is general agreement that electrodiagnostic studies still rank very high in their ability to provide the clinical neurophysiologist with a working diagnosis. A great limitation faced by these specialists is the paucity of normal values to be found in the literature for this very young age group. Many reasons account for that, and while some are similar for many age groups, they are particularly acute
https://doi.org/10.1016/j.clinph.2019.11.004 1388-2457/Ó 2019 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.
178
J.F. Jabre et al. / Clinical Neurophysiology 131 (2020) 177–182
in the pediatric subpopulations. These include the significant time investment necessary to collect normal values, the ability to define a ‘‘normal” population in this cohort whether by physical exam or a combination of physical and laboratory examination in healthy children, and last but not least, in the ability to obtain from a parent or guardian, institutional review board (IRB), and ethics committee approval to undertake such work. In this paper, we present the results of our work to derive normal values in the 3 years old for Median, Ulnar, Superficial Peroneal, Sural, and Medial Plantar sensory studies, and for Median, Ulnar, Peroneal, and Tibial motor studies., and for Median, Ulnar, Peroneal, and Tibial motor studies in this age group using the extrapolated norms, or e-norms method. The e-norms method (Jabre et al., 2015) has to date been validated by several workers in the field (Nandedkar et al., 2015, Pitt and Jabre, 2017, Jabre et al., 2016, Zaccarini et al., 2016, Jabre et al., 2016, Punga et al., 2019), and cited in the recently published ‘‘Standards for quantification of EMG and neurography” by Stålberg et al as one of the ‘‘Novel methods that do not require the tedious collection of reference values from healthy individuals..”(Stålberg et al., 2019). 2. Methods
Number of trials: Variable depending on the child and conditions investigated – sometimes single shocks were all that is possible, at other times averaging was possible. Usually we did not need more than 10. For motor studies, the amplitude (in mV) was measured from the pre-compound muscle action potential baseline at the takeoff latency to the first negative peak. The onset Latency (in ms) was measured from the onset of the stimulus artifact to the start of the first negative peak. Motor stimulation paradigms used were as follows:
Stimulus duration: 0.3 ms. Shape alternating polarity. Intensity: Usually under 15 mA – up to 50 mA rarely. Number of trials: Variable depending on the child and conditions investigated – always single shocks were given until we were certain that the stimulus was supramaximal.
Fixed distances between stimulation point and recording electrode placements were not used because of the variable size of the limbs in the age group of the children studied. Stimulation and recording landmarks and range of distances used were as follows:
2.1. Subjects All subjects were studied at the Great Ormond Street Hospital for Children NHS foundation trust, United Kingdom, between July 2007 and September 2013. Ages ranged from birth to 3 years of age. The great majority were examined by one of the authors (MCP) or under his close supervision. 2.2. Methods Analysis of the collected laboratory data for research purposes was obtained from the Joint Research and development office, Great Ormond Street Hospital for children. Upper and lower extremity sensory and motor nerve conduction studies were performed using a Dantec KeyPoint EMG machine (Alpine biomedical Aps, Tonsbakken 16–18, DK-2740, Skovlunde, Denmark). High and low band pass filter settings were 20 Hz and 5 kHz for sensory studies and 20 Hz and 10 kHz for motor studies. Handheld stimulators were used with disposable felt pads. According to the size of the limb there was a choice of the separation between active and reference electrode, which was either 10 or 25 mm. The recordings were made with disposable surface electrodes (Ambu blue sensor ref NF-10-SC/12 Ambu A/S, Baltorpbakken 13, DK-2750. Ballerup). The distances between G1 and G2 varied according to the age of the child. In the youngest children it was sometimes necessary to cut down the electrodes and the minimum distance was around 20 mm. The maximum distance used was 30 mm. For sensory studies, the amplitude (in mV) was measured between the negative peak to the midpoint of a line drawn between the lowest points of the positive waves one and two. The onset Latency (in ms) was measured from the onset of the stimulus artifact to the first positive peak and the conduction velocity was obtained by dividing the distance in mm, by the onset latency. Sensory stimulation paradigms used were as follows: Stimulus duration: 0.1 ms. Shape alternating polarity. Intensity: Usually under 15 mA – up to 50 mA rarely.
2.2.1. For the sensory studies Median palm to wrist study: Orthodromic stimulation was used stimulating the nerve in the palm between the flexor tendons to digits II and III and the response was recorded from the Median nerve with G1 placed on the most distal wrist crease at distances varying between 2.5 and 6 cm. Ulnar palm to wrist study: Orthodromic stimulation was used stimulating the nerve in the palm between the flexor tendons to digits IV and V with G1 placed on the medial aspect of most distal wrist crease with distances varying between 2.5 and 6 cm. Superficial Peroneal study: Antidromic stimulation was used stimulating the nerve on the lateral aspect of the lower leg recording and recording from the dorsum of the ankle joint midway between the two malleoli. Distances varied between 4 and 8 cm. Sural study: Antidromic stimulation was used stimulating the nerve on the Achilles tendon and recording from electrodes placed dorsal to the lateral malleolus with distances varying between 4 and 8 cm. Medial Plantar study: Orthodromic stimulation was used stimulating the nerve in the sole just lateral to the flexor tendon to the hallux and the response was recorded from the ankle with G1 placed posterior to the medial epicondyle with distances varying between 4 and 9 cm (Fig. 1). 2.2.2. For the motor studies During the distal stimulation for all of the motor nerves the distance between the stimulating electrode and the G1 electrode was not measured. The points of stimulation and the muscles used recording are given below for the nerves tested. Median study: The Median nerve was stimulated at the midpoint of the dorsal crease of the wrist and the response was recorded from the Abductor Pollicis Brevis (APB). Proximal stimulation was at the elbow crease medial to the brachial artery. Ulnar study: The Ulnar nerve was stimulated at the wrist lateral to the tendon of flexor carpi ulnaris and the response was recorded from the Abductor Digiti Minimi (ADM). At the elbow, stimulation was proximal to the olecranon just above the groove where the ulnar nerve passes. Peroneal study: The Peroneal nerve was stimulated at the dorsal aspect of the ankle midway between the malleoli and above the
J.F. Jabre et al. / Clinical Neurophysiology 131 (2020) 177–182
179
Fig. 1. Medial Plantar sensory recording in a five months old baby.
fibular head, and the response was recorded from the Extensor Digitorum Brevis (EDB) (Fig. 2). Tibial study: The Tibial nerve was stimulated at the ankle posterior to the medial malleolus and at the popliteal fossa and the response was recorded from the Abductor Hallucis (AH). 2.3. The e-norms method The e-norms method extracts a cohort’s normal values from data obtained in a laboratory population, which, for the purpose of this work, consisted of electrodiagnostic studies of sensory and motor nerve conductions in a pediatric cohort from birth to 3 years of age. The e-norms procedure can be performed using a simple Microsoft Excel spreadsheet uploaded anonymously and securely in under 20 minutes to an e-norms web application developed by one of the authors (JFJ) for this purpose (Jabre). To calculate a variable’s e-norms, the data is sorted in ascending order and plotted as a line graph. The plot reveals an inverted S curve with a steep lower
left, a middle ‘‘plateau,” and a steep upper right part. Data points that lie at the left and right extremes of the curve display higher consecutive or first order differences between them, while those that lie at the center plateau part display smaller consecutive or first order differences between them. The data that lie in the plateau part of the curve are considered to come from normal subjects within that cohort, and are extracted from the pool to calculate a variable’s normal values or e-norms (Fig. 3). 3. Results E-norms sensory and motor normal values were calculated in a cohort of pediatric patients seen between birth and 3 years of age, broken down as follows: 0–3 months, 3–6 months, 6–12 moths, 12–24 months; and 24–36 months. Tables 1 and 2 show the descriptive statistics of the nerve conduction e-norms obtained in this age group.
Fig. 2. Peroneal motor distal and proximal recordings (Extensor Digitorum Brevis) in a six months old baby.
180
J.F. Jabre et al. / Clinical Neurophysiology 131 (2020) 177–182
Fig. 3. Median Motor Amplitude e-norms. A user logs on to the web app and securely uploads an Excel spreadsheet containing the nerve conduction data variable to be analyzed. The app automatically plots the e-norms curve (left Y axis) and the first derivative of the consecutive data points (right Y axis). The X axis represents the variable’s rank. The user drags the mouse over the e-norms curve from the left to the right inflection points to delineate the plateau (which becomes highlighted by a rectangle). The app then automatically calculates the descriptive statistics of the data that lies within the plateau part of the curve (seen to the left of the plot).
Table 1 E-norms of sensory and motor upper extremity nerve conductions in 3 years old infants.
Median S (P-W) Onset Lat (ms) Median S (P-W) Amplitude (mV) 5th Percentile Amplitude (mV) Median S (P-W) CV (m/s)
0–3 months
3–6 months
6–12 months
12–24 months
24–36 months
0.9 ± 0.08 (74) 19.5 ± 6.5 (79) 12.6 44.9 ± 5.4 (24)
0.9 ± 0.09 (64) 23.5 ± 8.1 (72) 12.6 45 ± 5.3 (56)
0.9 ± 0.08 (89) 28.0 ± 7.8 (85) 14.3 48.6 ± 5.8 (101)
0.9 ± 0.08 (93) 28.0 ± 9.1 (90) 12.7 49.7 ± 6.4 (121)
0.9 ± 0.09 (106) 28.4 ± 10.0 (63) 15.1 50.8 ± 6.1 (98)
0–3 months
3–6 months
6–12 months
12–24 months
24–36 months
Ulnar S (P-W) Onset Lat (ms) Ulnar S (P-W) Amplitude (mV)
– –
0.8 ± 0.1 (8) 12.8 ± 3.6 (5)
0.8 ± 0.2 (5)
0.9 ± 0.1 (48) 14.2 ± 3.3 (26)
5th Percentile Amplitude (mV) Ulnar S (P-W) CV (m/s)
– –
9.0 49.1 ± 5.1 (9)
13.4+2.5 (4) 10.0 51.7 ± 9.7 (5)
0.8 ± 0.2 (19) 13.8 ± 4.1 (10) 8.5 56.7 ± 4.8 (20)
9.8 57.7 ± 8.0 (48)
0–3 months
3–6 months
6–12 months
12–24 months
24–36 months
2.1 ± 0.2 (29) 4.6 ± 1.7 (29)
2.1 ± 0.2 (21) 5.4 ± 1.7 (25)
2.1 ± 0.2 (27) 5.7 ± 1.7 (23)
2.1 ± 0.2 (39) 5.9 ± 1.8 (34)
2.1 ± 0.2 (54) 5.9 ± 1.9 (28)
0–3 months
3–6 months
6–12 months
12–24 months
24–36 months
1.9 ± 0.2 (29) 3.3 ± 0.9 (56)
1.9 ± 0.2 (17) 3.6 ± 1.1 (40)
1.9 ± 0.2 (25) 3.9 ± 1.2 (68)
1.9 ± 0.2 (56) 4.1 ± 1.1 (82)
1.9 ± 0.2 (46) 4.3 ± 1.1 (50)
Median M APB Onset Lat (ms) Median M APB Amplitude (mV)
Ulnar M ADM Onset Lat (ms) Ulnar M ADM Amplitude (mV)
Legend: E-norms are listed as mean ± standard deviation (number of studies), and sensory amplitudes 5th Percentile. S: Sensory. P-W: Palm-Wrist. Lat: Latency. CV: Conduction Velocity. M: Motor. APB: Abductor Pollicis Brevis. ADM: Abductor Digiti Minimi. Dash (–): Insufficient Data.
4. Discussion This study presents unique advantages for developing nerve conduction normal values in a very young age group between birth and 3 years. The values in this work were retrieved with the e-norms method, a novel previously unavailable technique to other authors, that allowed harnessing data from clinical neurophysiology studies of large cohorts of infants and children. All these studies were performed in a major pediatric hospital in the UK, the Great Ormond Street Hospital in London, by a single electromyographers (or under his direct supervision), using modern digital equipment, and single use stick-on surface electrodes as opposed to needle electrodes.
In the pediatric literature, numerous articles were published between the 1960s and 1990s in the English and French literatures on nerve conduction and EMG normal values in infants and children highlighting changes in these normative data with age due to peripheral nervous system maturation. Prominent among them were works by Gamstorp (1964), Gamstorp and Shelburne (1965), Gamstorp (1970), Dunn et al. (1964), Wagner and Buchthal (1972), Cruz Martinez et al. (1977), Martinez et al. (1978), Audry-Chaboud et al. (1984), Lang et al. (1985), Miller and Kuntz (1986), Parano et al. (1993). Little value can be added by comparing our results to theirs given their use of different, mostly analog devices in the early works, and different recording and analysis techniques ranging from a ‘‘polaroid camera” for action potential measurements, to
181
J.F. Jabre et al. / Clinical Neurophysiology 131 (2020) 177–182 Table 2 E-norms of sensory and motor lower extremity nerve conductions in 3 years old infants.
Sup Per S Onset Lat (ms) Sup Per S Amplitude (mV) 5th Percentile Amplitude (mV) Sup Per S CV (m/s)
Sural S Onset Lat (ms) Sural S Amplitude (mV) 5th Percentile Amplitude (mV) Sural S CV (m/s)
Med Plantar S Med Plantar S 5th Percentile Med Plantar S
Onset Lat (ms) Amplitude (mV) Amplitude (mV) CV (m/s)
Peroneal M EDB Onset Lat (ms) Peroneal M EDB Amplitude (mV)
Tibial M AH Onset Lat (ms) Tibial M AH Amplitude (mV)
0–3 months
3–6 months
6–12 months
12–24 months
24–36 months
– – – –
– 8.2 ± 3.8 (8) 3.0 42.8 ± 8.5 (7)
1.3 ± 0.5 (18) 13.8 ± 10.5 (18) 6.2 44.1 ± 7.2 (16)
1.3 ± 0.3 (80) 15.3 ± 12.4 (81) 6.0 49.0 ± 10.1 (78)
1.3 ± 0.3 (116) 17.8 ± 8.4 (115) 6.8 53.7 ± 9.7 (112)
0–3 months
3–6 months
6–12 months
12–24 months
24–36 months
– – – –
1.1 ± 0.2 (3) 8.4 ± 4.4 (3) 6.0 43.5 ± 4.1 (2)
1.2 ± 0.1 (17) 12.7 ± 6.4 (18) 6.0 44.4 ± 11.3 (17)
1.3 ± 0.8 (96) 15.5 ± 9.1 (97) 5.1 48.5 ± 8.7 (92)
1.3 ± 0.3 (63) 18.0 ± 8.4 (132) 6.2 50.2 ± 10.1 (130)
0–3 months
3–6 months
6–12 months
12–24 months
24–36 months
1.3 ± 0.3 (201) 8.4 ± 6.3 (213) 2.2 32.1 ± 8.9 (208)
1.3 ± 0.5 (145) 12.1 ± 11.2 (145) 3.5 40.7 ± 11.2 (143)
1.3 ± 0.2 (243) 13.3 ± 9.4 (244) 4.4 45.3 ± 9.3 (236)
1.3 ± 0.3 (373) 15.9 ± 10.0 (374) 5.8 50.8 ± 10.8 (369)
1.3 ± 0.3 (258) 16.0 ± 9.5 (258) 6.3 53.1 ± 12.6 (254)
0–3 months
3–6 months
6–12 months
12–24 months
24–36 months
2.0 ± 0.2 (9) 1.4 ± 0.4 (11)
2.0 ± 0.1 (11) 1.4 ± 0.5 (14)
2.0 ± 0.1 (29) 1.5 ± 0.5 (31)
2.0 ± 0.1 (55) 1.5 ± 0.4 (74)
2.0 ± 0.2 (40) 1.6 ± 0.5 (56)
0–3 months
3–6 months
6–12 months
12–24 months
24–36 months
2.4 ± 0.4 (133) 4.6 ± 1.7 (76)
2.5 ± 0.6 (85) 5.3 ± 1.7 (54)
2.5 ± 0.9 (100) 5.7 ± 1.7 (72)
2.6 ± 0.8 (128) 5.9 ± 1.8 (84)
2.7 ± 0.7 (73) 5.9 ± 1.9 (49)
Legend: E-norms are listed as mean ± standard deviation (number of studies), and sensory amplitudes 5th Percentile. Sup Per: Superficial Peroneal. S: Sensory. Lat: Latency. CV: Conduction Velocity. Med Plant: Medial Plantar. M: Motor. EDB: Extensor Digitorum Brevis. AH: Abductor Hallucis. Dash (–): Insufficient Data.
‘‘pipe-cleaners” and ‘‘copper-strips” for recording, and near nerve needle electrodes for both stimulation and/or recording. It is also worth noting that most of these studies showed differences in normal values among each other as well due to different cohorts, different equipment, and a variety of recording electrodes and analysis methods, not to mention differences in age group stratification used by various authors. While our results may not always be in agreement with these studies, they do show similar trends in the changes encountered with age, most commonly in motor and sensory conduction velocities. We do not see this as a downside however; the e-norms method’s main advantage is to make it easier for workers in the field to develop their own normal values, using their own equipment, stimulation and recording techniques and methods, and in their own patient population. More recently however, Ryan et al published a review of electronic medical records of nerve conduction studies of pediatric patients from birth to under 18 years of age whose EMG and nerve conduction studies were interpreted as normal between 1997 and 2017(Ryan et al., 2019). Of note is that they, like us, show low number of subjects (n) and large standard deviations in the younger age groups that invariably resulted in mean minus two standard deviations negative values in the Median and Peroneal motor amplitudes, and the Sural and Medial Plantar sensory amplitudes. They, like us, also indicated that ‘‘the sample sizes in these (early) normative studies were relatively small, especially when compared with the higher volumes seen in referral centers in recent years. Furthermore, many laboratories have reported their own pediatric reference values when discussing normal or abnormal electrodiagnostic results, without a clear explanation of the methodology used to obtain these values.” We feel these findings, in our study and theirs, are probably a reflection of the technical difficulties the EMGer encounters in this age group, due to movement, short limbs, poor tolerance of the study, and time limitations etc.. We postulate that the mean is probably a better measure of what one is to expect in this age group, since in studies that are technically difficult or clinically unreliable, the EMGer can easily determine the technical, as
opposed to the physiological nature of their findings, and disregard those findings accordingly. Finally, while this work describes the application of the e-norms method for sensory and motor nerve conduction normal values in a subgroup of pediatric patients 3 years of age, the e-norms method itself is ‘‘data neutral” and does not apply to Clinical Neurophysiology studies alone. It can also be used for other clinical and biomedical markers, its major advantage being that it can be performed quickly and easily on different types of numerical data. 5. Conclusions We used the e-norms method to derive sensory and motor nerve conduction studies reference values in the upper and lower extremity of a very young pediatric cohort 3 years of age referred to the Great Ormond Street Hospital for children NHS Foundation Trust, London, UK for diagnostic work-up. Performance of these studies in the very young can be a difficult undertaking and requires a great deal of patience and experience on the part of the clinical neurophysiologist. Declaration of Competing Interest None of the authors have any conflicts of interest to disclose. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. References Audry-Chaboud D, Soichot P, Giroud M, Nivelon JL. Interet de l’etude des vitesses de conduction nerveuse sensitive a l’aiguille chez l’enfant au-dessous de 3 ans. Rev Electroencephalogr Neurophysiol Clin 1984;13:336–9. Cruz Martinez A, Perez Conde MC, Ferrer MT. Motor conduction velocity and Hreflex in infancy and childhood: 1)–study in newborns, twins and small-fordates. Electromyogr Clin Neurophysiol 1977;17:493–505. Dunn HG, Buckler J, Morrison GC, Emery AW. Conduction velocity of motor nerves in infants and children. Pediatrics 1964;34:708–27. Gamstorp I. Conduction velocity of peripheral nerves in children. Trans Am Neurol Assoc 1964;89:198–9. Gamstorp I. Conduction velocity of peripheral nerves and electromyography in infants and children. Psychiatr Neurol Med Psychol Beih 1970;13–14:235– 244.
182
J.F. Jabre et al. / Clinical Neurophysiology 131 (2020) 177–182
Gamstorp I, Shelburne SA. Peripheral sensory conduction in ulnar and median nerves of normal infants, children, and adolescents. Acta Paediatr Scand 1965;54:309–13. Jabre J. Enorms [cited 2019 Aug 4]. Available from: https://enorms.com/. Jabre J, Kouyoumdjian J, Moreira Ferreira V. Carpal tunnel syndrome electrophysiological parameters acquired using the e-norms technique. Muscle Nerve 2016;54:546. Jabre JF, Pitt MC, Deeb J, Chui KKH. E-norms: a method to extrapolate reference values from a laboratory population. J Clin Neurophysiol 2015;32:265–70. Lang HA, Puusa A, Hynninen P, Kuusela V, Jäntti V, Sillanpää M. Evolution of nerve conduction velocity in later childhood and adolescence. Muscle Nerve 1985;8:38–43. Martinez AC, Perez Conde MC, del Campo F, Barrio M, Gutierrez AM, Lopez E. Sensory and mixed conduction velocity in infancy and childhood. I. Normal parameters in median, ulnar and sural nerves. Electromyogr Clin Neurophysiol 1978;18:487–504. Miller RG, Kuntz NL. Nerve conduction studies in infants and children. J Child Neurol 1986;1:19–26. Nandedkar SD, Sanders DB, koyoumdjian JA, Barkhaus PE, Stålberg EV. Confirming normal jitter limits using the extrapolated normal method. Muscle Nerve 2015;52:S30.
Parano E, Uncini A, De Vivo DC, Lovelace RE. Electrophysiologic correlates of peripheral nervous system maturation in infancy and childhood. J Child Neurol 1993;8:336–8. Pitt MC, Jabre JF. Determining jitter values in the very young by use of the e-norms methodology. Muscle Nerve 2017;55:51–4. Punga AR, Jabre JF, Amandusson Å. Facing the challenges of electrodiagnostic studies in the very elderly (>80 years) population. Clin Neurophysiol 2019;130:1091–7. Ryan CS, Conlee EM, Sharma R, Sorenson EJ, Boon AJ, Laughlin RS. Nerve conduction normal values for electrodiagnosis in pediatric patients. Muscle Nerve 2019;60:155–60. Stålberg E, van Dijk H, Falck B, Kimura J, Neuwirth C, Pitt M, et al. Standards for quantification of EMG and neurography. Clin Neurophysiol 2019;130:1688–729. Wagner AL, Buchthal F. Motor and sensory conduction in infancy and childhood: reappraisal. Dev Med Child Neurol 1972;14:189–216. Zaccarini C, Zheng C, Jabre J, Jiang J, Weber R, Zhu Y. Validation of the e-norms method to derive reference values of the Flexor Carpi Radialis H-Reflex latency. Muscle Nerve 2016;54:564.
Contents lists available at ScienceDirect
Clinical Neurophysiology journal homepage: www.elsevier.com/locate/clinph
Deriving pediatric nerve conduction normal values in the very young (<3 years) Joe F. Jabre a,⇑, Matthew C. Pitt b, Ralph Smith b a b
Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA Department of Clinical Neurophysiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom
a r t i c l e
i n f o
Article history: Accepted 10 November 2019 Available online 22 November 2019 Keywords: Pediatric normal values Sensory Motor Nerve conductions E-norms
h i g h l i g h t s Pediatric EMG is an essential part of the workup of children with neuromuscular disorders. The paucity of normal values in the <3 years old poses a limitation in the analysis of their tests. The e-norms method is a fast and efficient method to derive a lab’s own normal values.
a b s t r a c t Objective: This work describes our efforts to obtain nerve conduction studies normal values in a pediatric cohort between birth and 3 years of age using the extrapolated norms or e-norms method. Interpretation of these studies poses major challenges when no reliable normal values can be found in the literature. Methods: The e-norms method was used to derive a reference range of upper and lower extremity sensory and motor nerve conductions normal values from a pediatric cohort referred to an EMG Laboratory for nerve conduction studies. Results: E-norms were calculated for Median, Ulnar, Superficial Peroneal, Sural, and Medial Plantar sensory studies, and for Median, Ulnar, Peroneal, and Tibial motor studies. Conclusions: Pediatric electrodiagnostic testing is a very challenging undertaking. The ability to obtain and use normal values from the neurophysiologist’s own referral pool adds great value to their diagnostic work-up. Significance: EMG and nerve conduction studies can yield invaluable information in the diagnostic workup of young infants. Using the e-norms method improves on the analysis and interpretation of electrophysiological studies in this age group. Ó 2019 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.
1. Introduction The work-up of neuromuscular disorders in young children can be a daunting task. Sensory and motor nerve conductions can add valuable information to the diagnostic work-up of young children particularly in relationship to the investigation of peripheral neu-
Abbreviations: E-norms, Extrapolated norms; EMG, Electromyography; IRB, Institutional Review Board; S, Sensory; M, Motor; Lat, Latency; CV, Conduction Velocity; P-W, Palm-Wrist; Sup Per, Superficial Peroneal; Med Plant, Medial Plantar; APB, Abductor Pollicis Brevis; ADM, Abductor Digiti Minimi; EDB, Extensor Digitorum Brevis; AH, Abductor Hallucis. ⇑ Corresponding author at: 167 N Poinsettia Pl, Los Angeles, CA 90036, USA. E-mail address: [email protected] (J.F. Jabre).
ropathies and, if taken in conjunction with motor unit parameters and neuromuscular jitter measurements, in the whole range of neuromuscular diseases that occur in children. Even though some of these conditions are rare, most of these infants have symptoms from birth and an early diagnosis can add significant information to the choice of treatment given that some of these conditions can be associated with significant morbidity. Despite the progress in our ability to screen genetically for some disease entities, there is general agreement that electrodiagnostic studies still rank very high in their ability to provide the clinical neurophysiologist with a working diagnosis. A great limitation faced by these specialists is the paucity of normal values to be found in the literature for this very young age group. Many reasons account for that, and while some are similar for many age groups, they are particularly acute
https://doi.org/10.1016/j.clinph.2019.11.004 1388-2457/Ó 2019 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.
178
J.F. Jabre et al. / Clinical Neurophysiology 131 (2020) 177–182
in the pediatric subpopulations. These include the significant time investment necessary to collect normal values, the ability to define a ‘‘normal” population in this cohort whether by physical exam or a combination of physical and laboratory examination in healthy children, and last but not least, in the ability to obtain from a parent or guardian, institutional review board (IRB), and ethics committee approval to undertake such work. In this paper, we present the results of our work to derive normal values in the 3 years old for Median, Ulnar, Superficial Peroneal, Sural, and Medial Plantar sensory studies, and for Median, Ulnar, Peroneal, and Tibial motor studies., and for Median, Ulnar, Peroneal, and Tibial motor studies in this age group using the extrapolated norms, or e-norms method. The e-norms method (Jabre et al., 2015) has to date been validated by several workers in the field (Nandedkar et al., 2015, Pitt and Jabre, 2017, Jabre et al., 2016, Zaccarini et al., 2016, Jabre et al., 2016, Punga et al., 2019), and cited in the recently published ‘‘Standards for quantification of EMG and neurography” by Stålberg et al as one of the ‘‘Novel methods that do not require the tedious collection of reference values from healthy individuals..”(Stålberg et al., 2019). 2. Methods
Number of trials: Variable depending on the child and conditions investigated – sometimes single shocks were all that is possible, at other times averaging was possible. Usually we did not need more than 10. For motor studies, the amplitude (in mV) was measured from the pre-compound muscle action potential baseline at the takeoff latency to the first negative peak. The onset Latency (in ms) was measured from the onset of the stimulus artifact to the start of the first negative peak. Motor stimulation paradigms used were as follows:
Stimulus duration: 0.3 ms. Shape alternating polarity. Intensity: Usually under 15 mA – up to 50 mA rarely. Number of trials: Variable depending on the child and conditions investigated – always single shocks were given until we were certain that the stimulus was supramaximal.
Fixed distances between stimulation point and recording electrode placements were not used because of the variable size of the limbs in the age group of the children studied. Stimulation and recording landmarks and range of distances used were as follows:
2.1. Subjects All subjects were studied at the Great Ormond Street Hospital for Children NHS foundation trust, United Kingdom, between July 2007 and September 2013. Ages ranged from birth to 3 years of age. The great majority were examined by one of the authors (MCP) or under his close supervision. 2.2. Methods Analysis of the collected laboratory data for research purposes was obtained from the Joint Research and development office, Great Ormond Street Hospital for children. Upper and lower extremity sensory and motor nerve conduction studies were performed using a Dantec KeyPoint EMG machine (Alpine biomedical Aps, Tonsbakken 16–18, DK-2740, Skovlunde, Denmark). High and low band pass filter settings were 20 Hz and 5 kHz for sensory studies and 20 Hz and 10 kHz for motor studies. Handheld stimulators were used with disposable felt pads. According to the size of the limb there was a choice of the separation between active and reference electrode, which was either 10 or 25 mm. The recordings were made with disposable surface electrodes (Ambu blue sensor ref NF-10-SC/12 Ambu A/S, Baltorpbakken 13, DK-2750. Ballerup). The distances between G1 and G2 varied according to the age of the child. In the youngest children it was sometimes necessary to cut down the electrodes and the minimum distance was around 20 mm. The maximum distance used was 30 mm. For sensory studies, the amplitude (in mV) was measured between the negative peak to the midpoint of a line drawn between the lowest points of the positive waves one and two. The onset Latency (in ms) was measured from the onset of the stimulus artifact to the first positive peak and the conduction velocity was obtained by dividing the distance in mm, by the onset latency. Sensory stimulation paradigms used were as follows: Stimulus duration: 0.1 ms. Shape alternating polarity. Intensity: Usually under 15 mA – up to 50 mA rarely.
2.2.1. For the sensory studies Median palm to wrist study: Orthodromic stimulation was used stimulating the nerve in the palm between the flexor tendons to digits II and III and the response was recorded from the Median nerve with G1 placed on the most distal wrist crease at distances varying between 2.5 and 6 cm. Ulnar palm to wrist study: Orthodromic stimulation was used stimulating the nerve in the palm between the flexor tendons to digits IV and V with G1 placed on the medial aspect of most distal wrist crease with distances varying between 2.5 and 6 cm. Superficial Peroneal study: Antidromic stimulation was used stimulating the nerve on the lateral aspect of the lower leg recording and recording from the dorsum of the ankle joint midway between the two malleoli. Distances varied between 4 and 8 cm. Sural study: Antidromic stimulation was used stimulating the nerve on the Achilles tendon and recording from electrodes placed dorsal to the lateral malleolus with distances varying between 4 and 8 cm. Medial Plantar study: Orthodromic stimulation was used stimulating the nerve in the sole just lateral to the flexor tendon to the hallux and the response was recorded from the ankle with G1 placed posterior to the medial epicondyle with distances varying between 4 and 9 cm (Fig. 1). 2.2.2. For the motor studies During the distal stimulation for all of the motor nerves the distance between the stimulating electrode and the G1 electrode was not measured. The points of stimulation and the muscles used recording are given below for the nerves tested. Median study: The Median nerve was stimulated at the midpoint of the dorsal crease of the wrist and the response was recorded from the Abductor Pollicis Brevis (APB). Proximal stimulation was at the elbow crease medial to the brachial artery. Ulnar study: The Ulnar nerve was stimulated at the wrist lateral to the tendon of flexor carpi ulnaris and the response was recorded from the Abductor Digiti Minimi (ADM). At the elbow, stimulation was proximal to the olecranon just above the groove where the ulnar nerve passes. Peroneal study: The Peroneal nerve was stimulated at the dorsal aspect of the ankle midway between the malleoli and above the
J.F. Jabre et al. / Clinical Neurophysiology 131 (2020) 177–182
179
Fig. 1. Medial Plantar sensory recording in a five months old baby.
fibular head, and the response was recorded from the Extensor Digitorum Brevis (EDB) (Fig. 2). Tibial study: The Tibial nerve was stimulated at the ankle posterior to the medial malleolus and at the popliteal fossa and the response was recorded from the Abductor Hallucis (AH). 2.3. The e-norms method The e-norms method extracts a cohort’s normal values from data obtained in a laboratory population, which, for the purpose of this work, consisted of electrodiagnostic studies of sensory and motor nerve conductions in a pediatric cohort from birth to 3 years of age. The e-norms procedure can be performed using a simple Microsoft Excel spreadsheet uploaded anonymously and securely in under 20 minutes to an e-norms web application developed by one of the authors (JFJ) for this purpose (Jabre). To calculate a variable’s e-norms, the data is sorted in ascending order and plotted as a line graph. The plot reveals an inverted S curve with a steep lower
left, a middle ‘‘plateau,” and a steep upper right part. Data points that lie at the left and right extremes of the curve display higher consecutive or first order differences between them, while those that lie at the center plateau part display smaller consecutive or first order differences between them. The data that lie in the plateau part of the curve are considered to come from normal subjects within that cohort, and are extracted from the pool to calculate a variable’s normal values or e-norms (Fig. 3). 3. Results E-norms sensory and motor normal values were calculated in a cohort of pediatric patients seen between birth and 3 years of age, broken down as follows: 0–3 months, 3–6 months, 6–12 moths, 12–24 months; and 24–36 months. Tables 1 and 2 show the descriptive statistics of the nerve conduction e-norms obtained in this age group.
Fig. 2. Peroneal motor distal and proximal recordings (Extensor Digitorum Brevis) in a six months old baby.
180
J.F. Jabre et al. / Clinical Neurophysiology 131 (2020) 177–182
Fig. 3. Median Motor Amplitude e-norms. A user logs on to the web app and securely uploads an Excel spreadsheet containing the nerve conduction data variable to be analyzed. The app automatically plots the e-norms curve (left Y axis) and the first derivative of the consecutive data points (right Y axis). The X axis represents the variable’s rank. The user drags the mouse over the e-norms curve from the left to the right inflection points to delineate the plateau (which becomes highlighted by a rectangle). The app then automatically calculates the descriptive statistics of the data that lies within the plateau part of the curve (seen to the left of the plot).
Table 1 E-norms of sensory and motor upper extremity nerve conductions in 3 years old infants.
Median S (P-W) Onset Lat (ms) Median S (P-W) Amplitude (mV) 5th Percentile Amplitude (mV) Median S (P-W) CV (m/s)
0–3 months
3–6 months
6–12 months
12–24 months
24–36 months
0.9 ± 0.08 (74) 19.5 ± 6.5 (79) 12.6 44.9 ± 5.4 (24)
0.9 ± 0.09 (64) 23.5 ± 8.1 (72) 12.6 45 ± 5.3 (56)
0.9 ± 0.08 (89) 28.0 ± 7.8 (85) 14.3 48.6 ± 5.8 (101)
0.9 ± 0.08 (93) 28.0 ± 9.1 (90) 12.7 49.7 ± 6.4 (121)
0.9 ± 0.09 (106) 28.4 ± 10.0 (63) 15.1 50.8 ± 6.1 (98)
0–3 months
3–6 months
6–12 months
12–24 months
24–36 months
Ulnar S (P-W) Onset Lat (ms) Ulnar S (P-W) Amplitude (mV)
– –
0.8 ± 0.1 (8) 12.8 ± 3.6 (5)
0.8 ± 0.2 (5)
0.9 ± 0.1 (48) 14.2 ± 3.3 (26)
5th Percentile Amplitude (mV) Ulnar S (P-W) CV (m/s)
– –
9.0 49.1 ± 5.1 (9)
13.4+2.5 (4) 10.0 51.7 ± 9.7 (5)
0.8 ± 0.2 (19) 13.8 ± 4.1 (10) 8.5 56.7 ± 4.8 (20)
9.8 57.7 ± 8.0 (48)
0–3 months
3–6 months
6–12 months
12–24 months
24–36 months
2.1 ± 0.2 (29) 4.6 ± 1.7 (29)
2.1 ± 0.2 (21) 5.4 ± 1.7 (25)
2.1 ± 0.2 (27) 5.7 ± 1.7 (23)
2.1 ± 0.2 (39) 5.9 ± 1.8 (34)
2.1 ± 0.2 (54) 5.9 ± 1.9 (28)
0–3 months
3–6 months
6–12 months
12–24 months
24–36 months
1.9 ± 0.2 (29) 3.3 ± 0.9 (56)
1.9 ± 0.2 (17) 3.6 ± 1.1 (40)
1.9 ± 0.2 (25) 3.9 ± 1.2 (68)
1.9 ± 0.2 (56) 4.1 ± 1.1 (82)
1.9 ± 0.2 (46) 4.3 ± 1.1 (50)
Median M APB Onset Lat (ms) Median M APB Amplitude (mV)
Ulnar M ADM Onset Lat (ms) Ulnar M ADM Amplitude (mV)
Legend: E-norms are listed as mean ± standard deviation (number of studies), and sensory amplitudes 5th Percentile. S: Sensory. P-W: Palm-Wrist. Lat: Latency. CV: Conduction Velocity. M: Motor. APB: Abductor Pollicis Brevis. ADM: Abductor Digiti Minimi. Dash (–): Insufficient Data.
4. Discussion This study presents unique advantages for developing nerve conduction normal values in a very young age group between birth and 3 years. The values in this work were retrieved with the e-norms method, a novel previously unavailable technique to other authors, that allowed harnessing data from clinical neurophysiology studies of large cohorts of infants and children. All these studies were performed in a major pediatric hospital in the UK, the Great Ormond Street Hospital in London, by a single electromyographers (or under his direct supervision), using modern digital equipment, and single use stick-on surface electrodes as opposed to needle electrodes.
In the pediatric literature, numerous articles were published between the 1960s and 1990s in the English and French literatures on nerve conduction and EMG normal values in infants and children highlighting changes in these normative data with age due to peripheral nervous system maturation. Prominent among them were works by Gamstorp (1964), Gamstorp and Shelburne (1965), Gamstorp (1970), Dunn et al. (1964), Wagner and Buchthal (1972), Cruz Martinez et al. (1977), Martinez et al. (1978), Audry-Chaboud et al. (1984), Lang et al. (1985), Miller and Kuntz (1986), Parano et al. (1993). Little value can be added by comparing our results to theirs given their use of different, mostly analog devices in the early works, and different recording and analysis techniques ranging from a ‘‘polaroid camera” for action potential measurements, to
181
J.F. Jabre et al. / Clinical Neurophysiology 131 (2020) 177–182 Table 2 E-norms of sensory and motor lower extremity nerve conductions in 3 years old infants.
Sup Per S Onset Lat (ms) Sup Per S Amplitude (mV) 5th Percentile Amplitude (mV) Sup Per S CV (m/s)
Sural S Onset Lat (ms) Sural S Amplitude (mV) 5th Percentile Amplitude (mV) Sural S CV (m/s)
Med Plantar S Med Plantar S 5th Percentile Med Plantar S
Onset Lat (ms) Amplitude (mV) Amplitude (mV) CV (m/s)
Peroneal M EDB Onset Lat (ms) Peroneal M EDB Amplitude (mV)
Tibial M AH Onset Lat (ms) Tibial M AH Amplitude (mV)
0–3 months
3–6 months
6–12 months
12–24 months
24–36 months
– – – –
– 8.2 ± 3.8 (8) 3.0 42.8 ± 8.5 (7)
1.3 ± 0.5 (18) 13.8 ± 10.5 (18) 6.2 44.1 ± 7.2 (16)
1.3 ± 0.3 (80) 15.3 ± 12.4 (81) 6.0 49.0 ± 10.1 (78)
1.3 ± 0.3 (116) 17.8 ± 8.4 (115) 6.8 53.7 ± 9.7 (112)
0–3 months
3–6 months
6–12 months
12–24 months
24–36 months
– – – –
1.1 ± 0.2 (3) 8.4 ± 4.4 (3) 6.0 43.5 ± 4.1 (2)
1.2 ± 0.1 (17) 12.7 ± 6.4 (18) 6.0 44.4 ± 11.3 (17)
1.3 ± 0.8 (96) 15.5 ± 9.1 (97) 5.1 48.5 ± 8.7 (92)
1.3 ± 0.3 (63) 18.0 ± 8.4 (132) 6.2 50.2 ± 10.1 (130)
0–3 months
3–6 months
6–12 months
12–24 months
24–36 months
1.3 ± 0.3 (201) 8.4 ± 6.3 (213) 2.2 32.1 ± 8.9 (208)
1.3 ± 0.5 (145) 12.1 ± 11.2 (145) 3.5 40.7 ± 11.2 (143)
1.3 ± 0.2 (243) 13.3 ± 9.4 (244) 4.4 45.3 ± 9.3 (236)
1.3 ± 0.3 (373) 15.9 ± 10.0 (374) 5.8 50.8 ± 10.8 (369)
1.3 ± 0.3 (258) 16.0 ± 9.5 (258) 6.3 53.1 ± 12.6 (254)
0–3 months
3–6 months
6–12 months
12–24 months
24–36 months
2.0 ± 0.2 (9) 1.4 ± 0.4 (11)
2.0 ± 0.1 (11) 1.4 ± 0.5 (14)
2.0 ± 0.1 (29) 1.5 ± 0.5 (31)
2.0 ± 0.1 (55) 1.5 ± 0.4 (74)
2.0 ± 0.2 (40) 1.6 ± 0.5 (56)
0–3 months
3–6 months
6–12 months
12–24 months
24–36 months
2.4 ± 0.4 (133) 4.6 ± 1.7 (76)
2.5 ± 0.6 (85) 5.3 ± 1.7 (54)
2.5 ± 0.9 (100) 5.7 ± 1.7 (72)
2.6 ± 0.8 (128) 5.9 ± 1.8 (84)
2.7 ± 0.7 (73) 5.9 ± 1.9 (49)
Legend: E-norms are listed as mean ± standard deviation (number of studies), and sensory amplitudes 5th Percentile. Sup Per: Superficial Peroneal. S: Sensory. Lat: Latency. CV: Conduction Velocity. Med Plant: Medial Plantar. M: Motor. EDB: Extensor Digitorum Brevis. AH: Abductor Hallucis. Dash (–): Insufficient Data.
‘‘pipe-cleaners” and ‘‘copper-strips” for recording, and near nerve needle electrodes for both stimulation and/or recording. It is also worth noting that most of these studies showed differences in normal values among each other as well due to different cohorts, different equipment, and a variety of recording electrodes and analysis methods, not to mention differences in age group stratification used by various authors. While our results may not always be in agreement with these studies, they do show similar trends in the changes encountered with age, most commonly in motor and sensory conduction velocities. We do not see this as a downside however; the e-norms method’s main advantage is to make it easier for workers in the field to develop their own normal values, using their own equipment, stimulation and recording techniques and methods, and in their own patient population. More recently however, Ryan et al published a review of electronic medical records of nerve conduction studies of pediatric patients from birth to under 18 years of age whose EMG and nerve conduction studies were interpreted as normal between 1997 and 2017(Ryan et al., 2019). Of note is that they, like us, show low number of subjects (n) and large standard deviations in the younger age groups that invariably resulted in mean minus two standard deviations negative values in the Median and Peroneal motor amplitudes, and the Sural and Medial Plantar sensory amplitudes. They, like us, also indicated that ‘‘the sample sizes in these (early) normative studies were relatively small, especially when compared with the higher volumes seen in referral centers in recent years. Furthermore, many laboratories have reported their own pediatric reference values when discussing normal or abnormal electrodiagnostic results, without a clear explanation of the methodology used to obtain these values.” We feel these findings, in our study and theirs, are probably a reflection of the technical difficulties the EMGer encounters in this age group, due to movement, short limbs, poor tolerance of the study, and time limitations etc.. We postulate that the mean is probably a better measure of what one is to expect in this age group, since in studies that are technically difficult or clinically unreliable, the EMGer can easily determine the technical, as
opposed to the physiological nature of their findings, and disregard those findings accordingly. Finally, while this work describes the application of the e-norms method for sensory and motor nerve conduction normal values in a subgroup of pediatric patients 3 years of age, the e-norms method itself is ‘‘data neutral” and does not apply to Clinical Neurophysiology studies alone. It can also be used for other clinical and biomedical markers, its major advantage being that it can be performed quickly and easily on different types of numerical data. 5. Conclusions We used the e-norms method to derive sensory and motor nerve conduction studies reference values in the upper and lower extremity of a very young pediatric cohort 3 years of age referred to the Great Ormond Street Hospital for children NHS Foundation Trust, London, UK for diagnostic work-up. Performance of these studies in the very young can be a difficult undertaking and requires a great deal of patience and experience on the part of the clinical neurophysiologist. Declaration of Competing Interest None of the authors have any conflicts of interest to disclose. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. References Audry-Chaboud D, Soichot P, Giroud M, Nivelon JL. Interet de l’etude des vitesses de conduction nerveuse sensitive a l’aiguille chez l’enfant au-dessous de 3 ans. Rev Electroencephalogr Neurophysiol Clin 1984;13:336–9. Cruz Martinez A, Perez Conde MC, Ferrer MT. Motor conduction velocity and Hreflex in infancy and childhood: 1)–study in newborns, twins and small-fordates. Electromyogr Clin Neurophysiol 1977;17:493–505. Dunn HG, Buckler J, Morrison GC, Emery AW. Conduction velocity of motor nerves in infants and children. Pediatrics 1964;34:708–27. Gamstorp I. Conduction velocity of peripheral nerves in children. Trans Am Neurol Assoc 1964;89:198–9. Gamstorp I. Conduction velocity of peripheral nerves and electromyography in infants and children. Psychiatr Neurol Med Psychol Beih 1970;13–14:235– 244.
182
J.F. Jabre et al. / Clinical Neurophysiology 131 (2020) 177–182
Gamstorp I, Shelburne SA. Peripheral sensory conduction in ulnar and median nerves of normal infants, children, and adolescents. Acta Paediatr Scand 1965;54:309–13. Jabre J. Enorms [cited 2019 Aug 4]. Available from: https://enorms.com/. Jabre J, Kouyoumdjian J, Moreira Ferreira V. Carpal tunnel syndrome electrophysiological parameters acquired using the e-norms technique. Muscle Nerve 2016;54:546. Jabre JF, Pitt MC, Deeb J, Chui KKH. E-norms: a method to extrapolate reference values from a laboratory population. J Clin Neurophysiol 2015;32:265–70. Lang HA, Puusa A, Hynninen P, Kuusela V, Jäntti V, Sillanpää M. Evolution of nerve conduction velocity in later childhood and adolescence. Muscle Nerve 1985;8:38–43. Martinez AC, Perez Conde MC, del Campo F, Barrio M, Gutierrez AM, Lopez E. Sensory and mixed conduction velocity in infancy and childhood. I. Normal parameters in median, ulnar and sural nerves. Electromyogr Clin Neurophysiol 1978;18:487–504. Miller RG, Kuntz NL. Nerve conduction studies in infants and children. J Child Neurol 1986;1:19–26. Nandedkar SD, Sanders DB, koyoumdjian JA, Barkhaus PE, Stålberg EV. Confirming normal jitter limits using the extrapolated normal method. Muscle Nerve 2015;52:S30.
Parano E, Uncini A, De Vivo DC, Lovelace RE. Electrophysiologic correlates of peripheral nervous system maturation in infancy and childhood. J Child Neurol 1993;8:336–8. Pitt MC, Jabre JF. Determining jitter values in the very young by use of the e-norms methodology. Muscle Nerve 2017;55:51–4. Punga AR, Jabre JF, Amandusson Å. Facing the challenges of electrodiagnostic studies in the very elderly (>80 years) population. Clin Neurophysiol 2019;130:1091–7. Ryan CS, Conlee EM, Sharma R, Sorenson EJ, Boon AJ, Laughlin RS. Nerve conduction normal values for electrodiagnosis in pediatric patients. Muscle Nerve 2019;60:155–60. Stålberg E, van Dijk H, Falck B, Kimura J, Neuwirth C, Pitt M, et al. Standards for quantification of EMG and neurography. Clin Neurophysiol 2019;130:1688–729. Wagner AL, Buchthal F. Motor and sensory conduction in infancy and childhood: reappraisal. Dev Med Child Neurol 1972;14:189–216. Zaccarini C, Zheng C, Jabre J, Jiang J, Weber R, Zhu Y. Validation of the e-norms method to derive reference values of the Flexor Carpi Radialis H-Reflex latency. Muscle Nerve 2016;54:564.