Ultrasound reference values for peripheral nerve cross-sectional areas and indices in a sample of healthy individuals in Brazil

Voltan, Glauber; Bernardes-Filho, Fred; Lugão, Helena Barbosa; Nogueira-Barbosa, Marcello Henrique; Frade, Marco Andrey Cipriani

doi:10.1590/0100-3984.2022.0020

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Original Article • Radiol Bras 55 (6) • Nov-Dec 2022 • https://doi.org/10.1590/0100-3984.2022.0020 copy

Ultrasound reference values for peripheral nerve cross-sectional areas and indices in a sample of healthy individuals in Brazil

Valores de referência ultrassonográficos para áreas e índices de secção transversa de nervos periféricos em uma amostra de indivíduos brasileiros saudáveis

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Objective:

To establish peripheral nerve cross-sectional area (CSA) reference values (absolute values, measures of asymmetry, and measures of focality) for healthy individuals in Brazil.

Materials and Methods:

Sixty-six healthy volunteers underwent high-resolution ultrasound of the peripheral nerves. We obtained CSA measurements for three peripheral nerves, at specific locations: the median nerve, in the carpal tunnel (MT); the ulnar nerve, at the cubital tunnel site (UT) and at the pre-tunnel site (UPT); and the common fibular nerve, near the fibular head (FH). We calculated the CSA indices between the same sites on different sides (∆CSAs) and between the ulnar nerve tunnel and pre-tunnel sites on the same side (∆TPT).

Results:

A total of 132 neural sites were analyzed, and the following CSA values (mean ± SD, median) were obtained: MT (6.3 ± 1.9 mm², 6.0 mm²); UT (6.2 ± 1.6 mm², 6.1 mm²); UPT (5.6 ± 1.7 mm², 5.4 mm²); and FH (10.0 ± 3.7 mm², 9.9 mm²). The ∆CSA values

(mean ± SD, median) were as follows: MT (0.85 ± 0.7 mm², 0.95); UT (0.81 ± 0.62 mm², 0.95); UPT (0.61 ± 0.51 mm², 0.5); and FH (1.0 ± 0.77 mm², 1.0). The ∆TPT (mean ± SD, median) was (1.0 ± 0.8 mm², 1.0).

Conclusion:

Among individuals in Brazil, peripheral nerve CSA values tend to be higher among males and to increase with aging. However, the same does not appear to hold true for the ∆CSA or the ∆TPT, the exception being the difference between the right and left UT. Differences in CSA values greater than 2.5 mm² between sides or between sites along the same nerve can indicate asymmetry or focal thickening in neuropathy, respectively.

Keywords:
Peripheral nerves/diagnostic imaging; Ultrasonography/methods; Reference values.

Variable	Approach	Equation
Asymmetry	Ratio	= [maximum CSA (right/left)] - [minimum CSA (right/left)]
Asymmetry	Difference	∆MT = [maximum CSA MT (right/left)] - [minimum CSA MT (right/left)] ∆UT = [maximum CSA UT (right/left)] - [minimum CSA UT (right/left)] ∆UΡT = [maximum CSA UPT (right/left)] - [minimum CSA UPT (right/left)] ∆FH = [maximum CSA FH (right/left)] - [minimum CSA FH (right/left)]
Focality	Ratio	= [maximum CSA (UT/UPT)] - [minimum CSA (UT/UPT)]
Focality	Difference	∆TΡT = [maximum CSA (UT/UPT)] - [minimum CSA (UT/UPT)]

	Age range (years)					Upper limit (mean + 2 SD)
Variables	7-14	15-30	31-45	46-60	15-60	Upper limit (mean + 2 SD)
Sex
Male, n	6	12	4	6	22
Female, n	11	12	11	4	27
Total (R + L), n	34	48	30	20	98
Overall CSA, mean ± SD [median] CSA (mm²), mean ± SD [median]	11.7 ± 2.1 [12.0]	22.9 ± 4.6 [23.0]	37.0 ± 4.6 [36.0]	49.6 ± 2.5 [49.0]	27 ± 13 [25.0]
MT	5.5 ± 1.7 [5.0]	6.7 ± 2.0 [6.0]	6.8 ± 2.0 [6.2]	6.4 ± 1.2 [6.3]	6.6 ± 1.9 [6.0]	10.4
UT	5.2 ± 1.4 [6.0]	6.6 ± 1.7 [6.2]	6.6 ± 1.5 [6.7]	6.7 ± 1.0 [7.0]	6.7 ± 1.5 [6.1]	9.7
UPT	4.6 ± 1.2 [5.0]	6.3 ± 2.1 [5.8]	5.7±1.3 [5.6]	6.0±1.2 [6.3]	6.0 ± 1.7 [5.4]	9.4
FH	8.5 ± 3.0 [8.6]	10.7 ± 3.4 [11.0]	10.6 ± 4.8 [10.5]	10.9±2.9[10]	10.7 ± 3.8 [9.9]	18.3
∆CSA (mm²), mean ± SD [median]
MT	0.84 ± 0.6 [0.9]	0.6 ± 0.7 [0.4]	1.0 ± 0.7 [1.0]	0.9±0.8 [0.8]	0.8 ± 0.7 [0.9]	2.2
UT	0.6 ± 0.5 [1.0]	1.0 ± 0.7 [1.0]	0.8 ± 0.5 [0.9]	0.8±0.6 [0.7]	0.9 ± 0.6 [0.9]	3.1
UPT	0.6 ± 0.6 [0.3]	0.7 ± 0.4 [0.5]	0.6 ± 0.6 [0.4]	0.8±0.6 [0.5]	0.6 ± 0.4 [0.5]	1.4
FH	1.2 ± 0.9 [1.0]	0.9 ± 0.7 [0.75]	0.9 ± 0.6 [0.8]	1.1±0.8 [1.0]	0.9 ± 0.7 [1.0]	2.3
∆TPT (mm²), mean ± SD [median]	1.0 ±0.8 [1.0]	0.9 ± 0.8 [0.65]	1.2 ± 0.8 [1.1]	0.7±0.6 [0.6]	1.0 ± 0.8 [1.0]	2.6
CSA ratio, mean ± SD [median]
MT	1.2 ± 0.3 [1.2]	1.1 ± 0.1 [1.1]	1.2 ± 0.1 [1.1]	1.2±0.1 [1.1]	1.1 ± 0.14 [1.1]	1.38
UT	1.1 ± 0.1 [1.0]	1.2 ± 0.2 [1.2]	1.1 ± 0.1 [1.1]	1.1±0.1 [1.1]	1.1 ± 0.12 [1.1]	1.34
UPT	1.2 ± 0.2 [1.0]	1.1 ± 0.1 [1.1]	1.1 ± 0.1 [1.1]	1.0±0.0 [1.0]	1.13 ± 0.14 [1]	1.41
FH	1.2 ± 0.1 [1.1]	1.1 ± 0.1 [1.1]	1.1 ± 0.1 [1.1]	1.1±0.1 [1.0]	1.1 ± 0.10 [1.1]	1.3
TPT ratio, mean ± SD [median]	1.2 ± 0.2 [1.2]	1.2 ± 0.2 [1.1]	1.2 ± 0.2 [1.2]	1.1±0.2 [1.0]	1.2 ± 0.19 [1.2]	1.58

	Current study		Frade et al.(¹⁶16 Frade MAC, Nogueira-Barbosa MH, Lugão HB, et al. New sonographic measures of peripheral nerves: a tool for diagnosis of peripheric nerve involvment in leprosy. Mem Inst Oswaldo Cruz. 2013;108:257-62.)	Kerasnoudis et al.(¹³13 Kerasnoudis A, Pitarokoili K, Behrendt V, et al. Cross sectional area reference values for sonography of peripheral nerves and brachial plexus. Clin Neurophysiol. 2013;124:1881-8.)	Won et al.(¹⁸18 Won SJ, Kim BJ, Park KS, et al. Reference values for nerve ultrasonography in the upper extremity. Muscle Nerve. 2013;47:864-71.)	Qrimli et al.(²2 Qrimli M, Ebadi H, Breiner A, et al. Reference values for ultrasonography of peripheral nerves. Muscle Nerve. 2016;53:538-44.)
Parameter	Difference (∆)	Ratio	Difference (∆)	Ratio	Ratio	Difference, ∆
Equation	Maximum (R or L) - minimum (R or L)	Maximum (R or L) ∕ minimum (R or L)	Maximum (R or L) - minimum (R or L)	Side-to-side R/L	R - L ∕ (< R or L) × 100	Upper limit side-to-side
N	66	66	46 or 48^* * 46 for the UT and UPT; 48 for the MT and FH.	75	97	100
Age range (years)	15-60	15-60	≥ 18	≥ 18	20-69	≥ 18
CSA, mean ± SD
MT	0.85 ± 0.7	1.1 ± 0.14	1.0 ± 0.8	1.21 ± 0.04	-	3.3
UT	0.81 ± 0.62	1.1 ± 0.12	1.0 ± 0.7	1.2 ± 0.25	1.31 ± 0.25	2.5
UPT	0.61 ± 0.51	1.13 ± 0.14	0.9 ± 0.7	-	1.25 ± 0.2	2.5
FH	1.0 ± 0.77	1.1 ± 0.10	1.1 ± 1.1	1.19 ± 0.23	-	4.3
Ulnar TPT, mean ± SD	1.0 ± 0.81	1.2 ± 0.19	1.4 ± 1.1	1.5 ± 0.5	-	-

	Neural site
	MT				UT				UPT				FH
Reference	Nerves (n)	Mean	SD	P ^* * Results of the present study versus those of the studies included in the systematic review.	Nerves (n)	Mean	SD	P ^* * Results of the present study versus those of the studies included in the systematic review.	Nerves (n)	Mean	SD	P ^* * Results of the present study versus those of the studies included in the systematic review.	Nerves (n)	Mean	SD	P ^* * Results of the present study versus those of the studies included in the systematic review.
Lothet et al.(²⁹29 Lothet EH, Bishop TJ, Walker FO, et al. Ultrasound-derived nerve cross-sectional area in extremes of height and weight. J Neuroimaging. 2019;29:406-9.)	50	10	2.6	< 0.001	30	8.2	1.3	0.8	-	-	-	-	60	11.2	3.3	0.03
Bedewi et al.(²⁷27 Bedewi MA, Abodonya A, Kotb M, et al. Estimation of ultrasound reference values for the lower limb peripheral nerves in adults: a cross-sectional study. Medicine (Baltimore). 2018;97:e0179.)	138	9.8	2.8	< 0.001	138	7.5	2.3	< 0.001	138	7.6	2.6	< 0.001	138	8.9	3.2	0.006
Druzhinin et al.(²⁶26 Druzhinin D, Naumova E, Nikitin S. Nerve ultrasound normal values in children and young adults. Muscle Nerve. 2019;60:757-61.)	44^† † The authors considered only individuals ≥ 15 years of age (n = 22).	6.58	1.97	0.403	44^† † The authors considered only individuals ≥ 15 years of age (n = 22).	5.78	1.9	0.153	44^† † The authors considered only individuals ≥ 15 years of age (n = 22).	6.41	2.1	0.011	44^† † The authors considered only individuals ≥ 15 years of age (n = 22).	7.82	2.2	< 0.001
Kerasnoudis et al.(¹³13 Kerasnoudis A, Pitarokoili K, Behrendt V, et al. Cross sectional area reference values for sonography of peripheral nerves and brachial plexus. Clin Neurophysiol. 2013;124:1881-8.)	150	8	2	< 0.001	-	-	-	-	-	-	-	-	-	-	-	-
Cartwright et al.(²¹21 Cartwright MS, Shin HW, Passmore LV, et al. Ultrasonographic reference values for assessing the normal median nerve in adults. J Neuroimaging. 2009;19:47-51.)	100	9.8	2.4	< 0.001	-	-	-	-	-	-	-	-	-	-	-	-
Boehm et al.(¹⁰10 Boehm J, Scheidl E, Bereczki D, et al. High-resolution ultrasonography of peripheral nerves: measurements on 14 nerve segments in 56 healthy subjects and reliability assessments. Ultraschall Med. 2014; 35:459-67.)	56	8.5	1.8	< 0.001	56	7.6	2.1	< 0.001	56	6.3	1.6	0.009	56	8.9	2	0.037
Grimm et al.(²⁴24 Grimm A, Axer H, Heiling B, et al. Nerve ultrasound normal values - readjustment of the ultrasound pattern sum score UPSS. Clin Neurophysiol. 2018;129:1403-9.)	100^‡ ‡ The authors considered only the right side for neural site measurements; therefore, the number of individuals was equal to the number of nerves evaluated.	10.6	2.9	< 0.001	100^‡ ‡ The authors considered only the right side for neural site measurements; therefore, the number of individuals was equal to the number of nerves evaluated.	8.7	2.9	< 0.001	100^‡ ‡ The authors considered only the right side for neural site measurements; therefore, the number of individuals was equal to the number of nerves evaluated.	7	1.2	< 0.001	100^‡ ‡ The authors considered only the right side for neural site measurements; therefore, the number of individuals was equal to the number of nerves evaluated.	8.4	1.6	< 0.001
Frade et al.(¹⁶16 Frade MAC, Nogueira-Barbosa MH, Lugão HB, et al. New sonographic measures of peripheral nerves: a tool for diagnosis of peripheric nerve involvment in leprosy. Mem Inst Oswaldo Cruz. 2013;108:257-62.)	96	5.9	1.5	0.09	92	6.7	2.2	0.05	92	5.9	1.8	0.21	96	8.2	4.4	0.001
Qrimli et al.(²2 Qrimli M, Ebadi H, Breiner A, et al. Reference values for ultrasonography of peripheral nerves. Muscle Nerve. 2016;53:538-44.)	100^‡ ‡ The authors considered only the right side for neural site measurements; therefore, the number of individuals was equal to the number of nerves evaluated.	10.2	2.4	< 0.001	100^‡ ‡ The authors considered only the right side for neural site measurements; therefore, the number of individuals was equal to the number of nerves evaluated.	6.9	2.3	0.007	100^‡ ‡ The authors considered only the right side for neural site measurements; therefore, the number of individuals was equal to the number of nerves evaluated.	6.8	2.3	< 0.001	100^‡ ‡ The authors considered only the right side for neural site measurements; therefore, the number of individuals was equal to the number of nerves evaluated.	11.1	3.5	0.023
Won et al.(¹⁸18 Won SJ, Kim BJ, Park KS, et al. Reference values for nerve ultrasonography in the upper extremity. Muscle Nerve. 2013;47:864-71.)	194	8.3	1.5	< 0.001	-	-	-	-	194	5.8	1	0.18	-	-	-	-
Cartwright et al.(²⁰20 Cartwright MS, Passmore LV, Yoon JS, et al. Cross-sectional area reference values for nerve ultrasonography. Muscle Nerve. 2008;37: 566-71.)	-	--	-	-	-	-	-	-	-	-	-	-	120	11.2	3.3	0.007
Seok et al.(²³23 Seok HY, Jang JH, Won SJ, et al. Cross-sectional area reference values of nerves in the lower extremities using ultrasonography. Muscle Nerve. 2014;50:564-70.)	-	-	-	-	-	-	-	-	-	-	-	-	94^‡ ‡ The authors considered only the right side for neural site measurements; therefore, the number of individuals was equal to the number of nerves evaluated.	9.2	2.9	0.082
Tagliafico et al.(³²32 Tagliafico A, Cadoni A, Fisci E, et al. Reliability of side-to-side ultrasound cross-sectional area measurements of lower extremity nerves in healthy subjects. Muscle Nerve. 2012;46:717-22.)	80	8.2	2.3	< 0.001	80	5.9	3.0	0.344	-	-	-	-	120	11.4	8	0.072
Current study	132	6.3	1.9	-	132	6.2	1.6	-	132	5.6	1.7	-	132	10	3.7	-

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[1] Correspondence: Dr. Marco Andrey Cipriani Frade. Serviço de Dermatologia, Departamento de Clínica Médica - FMRP-USP. Avenida Bandeirantes, 3900, Monte Alegre. Ribeirão Preto, SP, Brazil, 14049-900. Email: mandrey@fmrp.usp.br.