The Egyptian Journal of Radiology and Nuclear Medicine (2013) 44, 563–572

Egyptian Society of Radiology and Nuclear Medicine

The Egyptian Journal of Radiology andNuclearMedicine

www.elsevier.com/locate/ejrnmwww.sciencedirect.com

ORIGINAL ARTICLE

Evaluation of median nerve in children with type1

diabetes using ultrasonographic imaging and

electrophysiology

Rania Refaata,*, Abeer Maghawry Abdelhameed

a, Nancy Samir Elbarbary

b,

Rana Ahmed El-Hilaly c

a Department of Radiodiagnosis, Ain Shams University, Cairo, Egyptb Department of Pediatrics, Pediatric Endocrinology and Diabetes Unit, Ain Shams University, Cairo, Egyptc Department of Physical Medicine, Rheumatology and Rehabilitation, Ain Shams University, Cairo, Egypt

Received 12 November 2012; accepted 4 June 2013Available online 3 July 2013

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KEYWORDS

Ultrasonography (US);

Nerve conduction study

(NCS);

Children type1 diabetes

(T1DM);

Cross-sectional area (CSA)

of median nerve

Corresponding author. Tel.:mail address: raniarefaat_19

er review under responsibility

uclear Medicine.

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Abstract Background: Diabetic peripheral neuropathy (DPN) is a worldwide costly complication

of diabetes.

Objective: To evaluate the relationship between the sonographically measured cross-sectional area

(CSA) of the median nerve and nerve conduction study (NCS) in children with type1 diabetes

(T1DM) complaining of DPN.

Material and methods: Forty childrenwithT1DMand20age-matchedhealthy subjectswere enrolled

in this study.Thediabetic childrenweredivided into2groups (without andwithDPN).All participants

underwent NCS and sonographic measurement of CSA for the median nerve in the carpal tunnel.

Results: TheCSA of themedian nerve in children withDPNwas higher than that in the control subjects

yetwithnosignificantdifferencewiththatofchildrenwithoutDPN.TheincreasedmediannerveCSAinthe

carpal tunnel was considerably correlated with the median nerve motor latency and duration of diabetes,

nevertheless, with no correlation with median nerve motor conduction velocity (MNCV).

Conclusion: Sonographic measurement of CSA of the median nerve in the carpal tunnel serves as a good

discriminator for diabetic children from healthy individuals. Moreover, it has significant positive correla-

tion with duration of disease and the nerve motor latency.� 2013 Production and hosting by Elsevier B.V. on behalf of Egyptian Society of Radiology and Nuclear

Medicine.

5285089.ail.com (R. Refaat).

tian Society of Radiology and

g by Elsevier

ing by Elsevier B.V. on behalf of Egyptian Society of Radiology and Nuclear Medicine.

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564 R. Refaat et al.

1. Introduction

The World Health Organization estimates that more than 220million people worldwide have diabetes mellitus (DM) (1).

Furthermore, International Diabetes Federation states 78,000children develop T1DM every year (2).

Diabetic neuropathy is recognized as the most common

clinical picture of nervous system disorders caused by DM(3) and is considered the most common type of neuropathies.It affects patients with both type1 and type2 diabetes, but itprogresses more rapidly and its manifestations are more severe

in T1DM (4). Earlier observations and population-based co-hort studies have shown that 66% of patients who haveT1DM develop some form of neuropathy (5).

For the evaluation of peripheral neuropathy (PN), physi-cians traditionally relied primarily on information gained froman accurate clinical history, a thorough physical examination

and electrodiagnostic testing with NCS (6,7). However, suchdiagnostic tests and studies do not provide spatial informationregarding the nerve and the surrounding structures (8). Ultra-

sonography (US) provides a rapid, cheap and non invasivemethod for the examination of the soft tissue structures ofthe wrist as it easily detects the median nerve which is locateddeep to the retinaculum (9).

A sophisticated search revealed a limited knowledge of dia-betic peripheral neuropathy (DPN) in children and a largelyvariable reported prevalence of PN in different studies of pedi-

atric patients with T1DM. Moreover, these children are moreprone to complications because of the early onset of diabetesand accordingly, to assure them of a better life style through

early detection and proper management of the complicationsof the PN.

Thus, our hypothesis is to demonstrate the relationship be-

tween the sonographically measured CSA of the median nervein children with T1DM complaining of DPN and the results ofNCS.

2. Materials and methods

We conducted the study on 40 eligible consecutive patientswith type1 diabetes [10 males, 30 females (mean age

15.2 ± 2.9 years; range: 7–18 years)] recruited from the regularattendants of the Pediatric Diabetes Clinic, Children’s Hospi-tal between June 2011 and January 2012. These patients were

included in the order that they showed up in the diabetes clinic.To be eligible for the study patients had to satisfy the fol-

lowing criteria: (1) children with T1DM, who are able to per-

form all neurological examinations and tests and (2) havingdiabetes for more than five years. We divided the diabetic chil-dren into 2 groups; children with and without diabetic periph-eral neuropathy (DPN). DPN was diagnosed on the basis of

sensory symptoms in the form of bilateral tingling and numb-ness which started a few months ago. Complete history takingwas performed including age, diabetes duration, complications

and insulin regimen for the 40 diabetic patients.Full clinical neurological examination was done to confirm

peripheral neuropathy if present. We adopted the simple rapid

bedside neuropathy disability score (NDS) as a screening toolfor DPN (10). The NDS was derived from the examination ofvibration perception (by means of a 128-Hz tuning fork), pin-

prick and temperature perceptions in the great toe and the

presence or absence of ankle reflexes. The sensory modalitieswere scored as either present (0) or reduced or absent (1) foreach leg. This means that ‘‘reduced’’ was scored as (1) indicat-

ing involvement of the nerve. Ankle reflexes were scored asnormal (0), present with reinforcement (1) or absent (2) foreach leg. The total maximal abnormal score was 10. A score

above 2 was defined as clinical DPN (11).Exclusion of neuropathies other than DPN was considered.

This includes the following: patients with other significant

chronic diseases (renal, liver and thyroid diseases) and othersystemic diseases that affect the central nervous system. Inaddition, history of familial neuropathy, other neurologicaldiseases, alcohol consumption, medications and exposure to

toxins (known to cause neuropathy), patients with mentalretardation or psychiatric diseases were excluded. Anthropo-metric measures; weight in kg, height in cm and body mass in-

dex (BMI); were calculated as weight in kilograms divided bysquare of height in meters, which were measured and recorded.

Other microvascular complications were screened including

diabetic retinopathy (DR) that was diagnosed by doing com-plete ocular examination and indirect ophthalmoscopy. Fur-ther urinary albumin excretion was measured by the

immuno-turbidimetric method for the detection of diabeticnephropathy. The kit used was from SERA-PAK (Bayer Cor-poration, Bendict Ave., Tarrytown, NY, USA). The result wasexpressed as albumin to creatinine ratio (ACR) in urine to

avoid diurnal variation in albumin excretion. Urinary creati-nine was estimated on Synchron C·7 (Beckman InstrumentsInc., Brea., CA, USA). Venous blood samples were obtained

in the morning from all patients after an overnight fast. A2 ml blood sample was drawn from peripheral veins undercomplete aseptic conditions. The tube was placed on EDTA

for the direct assay of HbA1c. The average of HbA1c measure-ments was determined and calculated for each patient (fourdeterminations per year) with an average length of three

months between each HbA1c measurement.For comparison, we enrolled 20 age-matched healthy sub-

jects (12 males and 8 females) with no obvious medical disor-der and not receiving any medication who served as a control

group. This group included children recruited from the sameregion as the case subjects; most were classmates or acquain-tances of the case subjects. They were age–BMI – matched

healthy individuals with a mean age of 13.9 ± 3.3 years; range:7–17 years. We studied a total of 120 upper limbs in all 60 sub-jects who underwent median NCS and sonographic measure-

ment of the median nerve CSA about 5 cm proximal to thewrist (in the carpal tunnel). These investigations were doneconcurrently in the same day.

The study protocol was approved by the Committee of Eth-

ics and the parents of all study participants; the patients andthe control subjects gave their written informed consent.

2.1. Sonographic measurement of the median nerve cross-sectional area (CSA)

Sonographic examination was performed unbiased to patient’s

history and NCS results using a Philips HD11 Revision 1.0.9imaging system with an L12-3 linear array probe and a B modereal time apparatus. The examiners had a board-certified

license and more than 10 years of experience. Patients wereseated in a chair with arms extended, hands resting in a

Fig. 1b Normal sonographic appearance of transverse scan of

the median nerve (MN) in the wrist of a child of the control group;

showing multiple hypoechoic bands corresponding to neuronal

fascicles which are separated by hyperechoic lines that correspond

to the epineurium.

Fig. 1c Normal transverse scan of the median nerve (MN) in the

wrist of a child of the control group; showing its normal elliptic

outline.

Evaluation of median nerve in children with type1 diabetes using ultrasonographic imaging and electrophysiology 565

horizontal supine position on the examination couch andfingers semiextended (12). We performed longitudinal(Fig. 1a) and transverse scans of the median nerve about

5 cm proximal to the wrist (in the carpal tunnel).We traced the median nerve through its course as follows. It

crosses superficially to the brachial artery at the mid-humerus

to lie on its medial side. The nerve enters the forearm betweenthe heads of pronator teres, the deeper of which separates itfrom the ulnar artery, while, at the wrist, the median nerve be-

comes superficial on the ulnar side of flexor carpi radialis, ex-actly in the midline (13). Accordingly, advanced sonographictechniques such as color Doppler and power Doppler imagingwere used in this study in order to identify the median nerve in

children with poor sonographic images.The normal appearance of the peripheral nerve should be

readily recognized as it consists of multiple hypoechoic bands

corresponding to neuronal fascicles, which are separated byhyperechoic lines that correspond to the epineurium(Fig. 1b) (14). The median nerve lies within the carpal tunnel

just to the radial side of the superficial row of flexor digitorumtendons. On transverse sonograms, the nerve appears elliptic inoutline (Fig. 1c) (9).

We measured median nerve CSA at the inner border of thethin hyperechoic rim of the nerve (perineurium) using the man-ual tracing technique (Fig. 1d) as according to Hammer et al.(15), this method of measurement of median nerve CSA yields

the most correct CSA. The weight of the probe was also ap-plied without additional pressure.

Fig. 1d Measurement of the median nerve (MN) CSA in the

wrist at the inner border of the thin hyperechoic rim of the nerve

(perineurium) using the manual tracing technique in a child of the

control group being 0.039 cm2.

2.2. Nerve conduction study

The nerve conduction study was performed with conventionalprocedure using the Schwarzer Topaz machine, Germany.

NCS was done on both median nerves measuring the motornerve conduction velocity (MNCV) and the motor latencyfrom the elbow to the wrist joint in a room with ambient tem-

perature of 25 �C and skin surface temperature between 31 �Cand 33 �C. The pick up (active) electrode was placed on theprominence of abductor pollicis brevis muscle. The referencewas placed on the distal phalanx of the thumb. The ground

electrode was placed between the active and the stimulator.The distal stimulation was applied 8 cm proximal to the activeelectrode and is placed between the flexor carpi radialis and

palmaris longus tendons. The proximal stimulation was ap-plied in the medial aspect of the antecubital fossa just lateralto the brachial artery.

Fig. 1a Normal sonographic appearance of longitudinal scan of

the median nerve (MN) in the wrist of a child of the control group.

2.3. Statistical analysis

SPSS statistics (V. 19.0, IBM Corp., USA, 2010) was used fordata analysis. Data were expressed as Mean ± SD for quanti-tative parametric measures and both number and percentagefor categorized data. For comparison between two indepen-

dent mean groups for parametric data, Student’s t test wasused, while, Wilcoxon Rank Sum test was used for comparisonbetween two independent groups for non-parametric data.

Additionally, Ranked Spearman’s correlation test was appliedto study the possible association between each of the two vari-ables among each group for non-parametric data. Chi-square

test was applied, as well, to study the association between eachof the two variables or comparison between two independentgroups as regards the categorized data.

The probability of error (p value) at 0.05 was consideredsignificant, while, at 0.01 and 0.001 was considered highlysignificant. To obtain the most sensitive and specific cut-offvalue for the sonographically measured CSA of the median

566 R. Refaat et al.

nerve, Diagnostic Validity Test was used and ROC wasconstructed. AUC was calculated to evaluate the most discrim-inating markers between the compared groups.

3. Results

Demographic data for the diabetic children and the control

individuals were recorded as shown in Table 1. There wereno significant differences in age, height, weight and BMI be-tween the diabetic children and the healthy subjects.

Patients with type1 diabetes were 10 males and 30 females.It is not surprising that in this series, there is a predominanceof females (75%) in T1DM cohort. It was previously reported

that unlike many other autoimmune diseases, where femalesare more at risk of disease, T1DM subgroups have a similargender distribution when diagnosed under age 15 with

T1DM. However, a minor male excess in incidence has beenreported in Europe and in populations of European originand as light female excess in populations of African or Asianorigin (16).

The included patients used human insulin in a dose rangingfrom 0.5 to 2.5 IU/kg/day with a mean of 1.8 ± 0.38 IU/kg/day; all of them were on intensive insulin therapy. 28 patients

were on preprandial injections of short-acting insulin andintermediate acting insulin (isophane NPH insulin) and 12 pa-tients were on long acting insulin analog (insulin glargine –

Aventis Pharma) at bedtime and preprandial short acting insu-lin analog. Of the 40 patients who were enrolled in the study,13 patients (32.5%) exhibited diabetic nephropathy in the formof microalbuminuria with a mean range of 90 ± 57.4 (mg/l)

and none had macroalbuminuria. 4 patients had bothnephropathy and peripheral neuropathy (10%). None of theenrolled patients had diabetic retinopathy.

By using Pearson Chi-Square test, there was a significantdifference (p = 0.024) between ratio of females to males inchildren without and with diabetic peripheral neuropathy

(DPN). Children without DPN group comprised of 14 females(70%) and 6 males (30%) and children with DPN group com-prised of 16 females (80%) and 4 males (20%), while, control

individuals comprised of 8 females (40%) and 12 males (60%).The sonographically measured CSA and the NCS results

for the diabetic children and the healthy subjects are shownin Table 2.

Comparison between control individuals versus childrenwithout DPN, control individuals versus children with DPNand children without DPN versus children with DPN concern-

ing the mean value of median nerve CSA, the mean value ofmedian nerve motor latency and the mean value of median

Table 1 Detailed demographic data of the study subjects.

Variable Control individuals

n 20

Sex, male/female 12/8

Age, y ± SD 13.9 ± 3.3

Height, cm ± SD 158 ± 6.5

Weight, kg ± SD 55.2 ± 11.2

Body mass index ± SD 20.1 ± 2.7

Duration of diabetes, y ± SD NA

NA, not applicable; SD, standard deviation.

nerve motor nerve conduction velocity (MNCV) were done.The results are summarized in Table 3 according to the valueof the probability of error (p value) to express the significance

of the difference between the compared groups.The mean median nerve CSA in the control individuals

showed statistically highly significant difference (p = 0) com-

pared to that of children without (Fig. 2) and with DPN(Fig. 3) as it was 0.043 versus 0.072 cm2 and 0.073 cm2 respec-tively. There was no statistical significance (p= 0.828) be-

tween mean median nerve CSA of children without DPNand that of children with DPN being 0.072 cm2 versus0.073 cm2.

The mean value of median nerve motor latency in the con-

trol individuals showed statistically highly significant differ-ence compared to that of children without (p= 0.001) andwith DPN (p= 0.005) as it was 2.96 ms versus 3.4 ms and

3.5 ms respectively. There was no statistical significance(p = 0.747) between the mean value of median nerve motor la-tency of children without DPN and that of children with DPN

being 3.4 ms versus 3.5 ms.The mean value of median nerve MNCV in the control

individuals showed statistically no significant difference

(p = 0.085) compared to that of children without DPN andstatistically significant difference (p = 0.016) compared to thatof children with DPN as it was 54.6 m/s versus 52.9 m/s and54.6 m/s versus 51.5 m/s respectively. There was no statistical

significance (p = 0.312) between the mean value of mediannerve MNCV of children without DPN and that of childrenwith DPN being 52.9 m/s versus 51.5 m/s.

There was a non significant difference between childrenwithout DPN (p = 0.14) and those with DPN (p= 0.549)regarding the mean value of HbA1c and duration of diabetes,

yet the values of HbA1c were higher in children with DPN.In the group of children without DPN, the mean median

nerve motor latency for both wrists had no correlation with

duration of diabetes (r= 0.327; p = 0.159) and HbA1c(r = 0.148; p = 0.534). The mean median nerve MNCV forboth wrists had no correlation with duration of diabetes(r = �0.375; p= 0.103) and a highly significant negative cor-

relation with HbA1c (r= �0.626; p = 0.003). The mean med-ian nerve CSA for both wrists had no correlation withduration of diabetes (r = �0.111; p = 0.642) and no correla-

tion with HbA1c (r= 0.399; p = 0.082).In the group of children with DPN, the mean median nerve

motor latency for both wrists had no correlation with the dura-

tion of diabetes (r= 0.163; p = 0.494) and HbA1c (r= 0;p= 1). The mean median nerve MNCV for both wrists hada highly significant negative correlation with duration of dia-

Children without DPN Children with DPN

20 20

6/14 4/16

15.9 ± 2.7 14.6 ± 3.5

162 ± 4.5 151.5 ± 8.8

63.2 ± 9.2 50.4 ± 18.8

24 ± 3.2 21.7 ± 7.2

8.6 ± 3.8 8.5 ± 3.7

Table 2 Sonographically measured CSA and NCS results in the study subjects.

Parameter Control individuals Children without DPN Children with DPN

Mean sonographically measured CSA, cm2 ± SD 0.043 ± 0.016 0.072 ± 0.021 0.073 ± 0.0175

Electrophysiologic measurement of mean motor latency, ms ± SD 2.96 ± 0.45 3.4 ± 0.50 3.5 ± 0.47

Electrophysiologic measurement of mean MNCV, m/s ± SD 54.6 ± 1.8 52.9 ± 3.8 51.5 ± 5.06

Table 3 Comparison between control individuals, children without DPN and children with DPN concerning the mean value of

median nerve CSA, the mean value of median nerve motor latency and the mean value of median nerve MNCV.

Parameter The mean value of

median nerve CSA

The mean value of median

nerve motor latency

The mean value of

median nerve MNCV

Control individuals versus

children without DPN

HS (p= 0) HS (p = 0.001) NS (p= 0.085)

Control individuals versus

children with DPN

HS (p= 0) HS (p = 0.005) S (p= 0.016)

Children without DPN versus

children with DPN

NS (p= 0.828) NS (p = 0.747) NS (p= 0.312)

HS, highly significant; S, significant; NS, non significant.

Evaluation of median nerve in children with type1 diabetes using ultrasonographic imaging and electrophysiology 567

betes (r= �0.566; p= 0.009) and HbA1c (r= �0.733;p = 0). The mean median nerve CSA for both wrists had no

correlation with HbA1c (r= � 0.438; p= 0.054) and a signif-icant positive correlation with the duration of diabetes(r= 0.46; p = 0.041).

In the group of the control individuals, the mean mediannerve CSA for both wrists had no correlation with mean med-ian nerve MNCV for both wrists (r= �0.176; p = 0.457) and

a highly significant positive correlation with mean mediannerve motor latency for both wrists (r= 0.778; p= 0).

In the group of children without DPN, the mean mediannerve CSA for both wrists had no correlation with mean med-

ian nerve motor latency for both wrists (r= 0.17; p = 0.473)and with mean median MNCV for both wrists (r = �0.358;p = 0.122).

In the group of children with DPN, the mean median nerveCSA for both wrists had a highly significant positive correla-tion with median nerve motor latency for both wrists

(r= 0.735; p = 0) (Fig. 4) and no correlation with mean med-ian MNCV for both wrists (r= �0.079; p= 0.741).

We found that the best cut-off value of the sonographicallymeasured median nerve CSA between control individuals and

children without DPN is 0.0435 (0.044) (Fig. 5) (i.e. >(0.044)identify children without DPN & <(0.044) identify controlindividuals with sensitivity = 100%, specificity = 70%, posi-

tive predictive value = 76.9%, negative predictive va-lue = 100% and efficacy or diagnostic accuracy = 85%.

We found that the best cut-off value of the sonographically

measuredmedian nerveCSA for discrimination between controlindividuals and children with DPN is 0.0455 (0.046) (Fig. 6) (i.e.>(0.046) identify children with DPN and <(0.046) identify

control individuals with sensitivity = 100%, specific-ity = 80%, positive predictive value = 83.3%, negative predic-tive value = 100% and efficacy or diagnostic accuracy = 90%.

Additionally, we found that the best cut-off value of the

mean median nerve motor latency of both wrists between con-trol individuals and diabetic children whether without or with

DPN is 3 (i.e. >3) identify diabetic children (without DPN orwith DPN) and <(3) identify control individuals with sensitiv-

ity = 80%, specificity = 70%, positive predictive va-lue = 72.7%, negative predictive value = 77.8% and efficacyor diagnostic accuracy = 75%.

In our study, no cut-off value was found regarding themean median nerve CSA of both wrists and the mean mediannerve motor latency of both wrists for discrimination between

diabetic children without and with DPN. Moreover, we didnot find any cut-off value regarding the mean median nerveMNCV of both wrists for discrimination between controlindividuals and diabetic children whether without or with

DPN nor between diabetic children without and with DPN.These are because no statistically significant difference wasfound between the compared groups regarding the previously

mentioned parameters.

4. Discussion

Between 2010 and 2030, there will be a 69% increase in thenumber of adults (aged 20–79 years) with diabetes in develop-ing countries and a 20% increase in developed countries. These

predictions indicate a growing burden of diabetes, particularlyin developing countries. Also, the prevalence of diabetes ad-justed to national population in Egypt in 2010 is 10.4% and

expected to be 12.8% in 2030. Additionally, estimated diabetesnumbers among adults aged 20–79 years will be changed from4.787 million in 2010 to 8.615 million in 2030 with a mean an-nual increment of 191 (17).

Diabetic peripheral neuropathy (DPN) is a common, dis-abling and costly complication of diabetes mellitus (18). Theprevalence of diabetic neuropathy also increases with time

and poor glycemic control (19–21) and severe diabetic poly-neuropathy can develop in young adults within a few monthsafter the onset of T1DM if the diabetes is poorly controlled

(22).

Fig. 2 The median nerve (MN) CSA in a child without DPN: (A) Transverse scan of the median nerve in the wrist showing the neuronal

fascicles and the epineurium. (B) The sonographically measured CSA at the inner border of the perineurium using the manual tracing

technique was 0.071 cm2.

568 R. Refaat et al.

More than 80% of patients with clinical diabetic neuropa-thy have a distal symmetrical form of the disorder (23,24). Inthis neuropathic pattern, signs and symptoms start and remain

more pronounced in the feet and go on to affect more proximalparts of the lower limbs and eventually the distal parts of theupper limbs (25).

The diagnosis of diabetic neuropathy is based on its charac-teristic symptoms and can be confirmed with NCS (5,26–28).Although, NCS is generally considered to be the most sensitivefor detecting and monitoring DPN, its utilization in patients

with diabetes is low (18). This is presumably because theNCS is time-consuming, slightly invasive and generally notwell tolerated for repeated evaluations (29).

Sonographic examinations can be performed to assessperipheral nerves and have already been used for the evalua-tion of disorders of the peripheral nervous system (30–36). Ad-

vances in ultrasound technology have made it possible toachieve a good spatial resolution for clear evaluation of theperipheral nerves. Wide availability, low cost, non invasive-

ness, being painless and short examination time are the advan-tages of sonography (37). Though, US is operator dependent,it shows high reproducibility after adequate training of theoperators (38).

As sonography is a non invasive method, it can be usedfor the measurement of the nerve CSA providing importantadditional information in patients with suspected neuropa-

thy. Sonographic measurements of the nerve CSA include

two methods: the indirect method (ellipsoid formula) (CSA(mm2) = major axis · minor axis · p · l/4) and the directmethod (tracing) (36). Recently, Aleman et al. (39) reported

that sonography for median nerve CSA measurements werereproducible either by tracing or by indirect method when astandardized sonographic examination protocol was used.

We used the direct method (tracing) for the examinationand measured it about 5 cm from the wrist (in the carpaltunnel).

The mechanism of diabetic neuropathy involves the patho-

genesis of damage to the pain mechanism, which is multifacto-rial and includes metabolic disturbances such ashyperglycemia, even impaired glucose tolerance, dyslipidemia,

oxidative and nitrosative stress, growth factor deficiencies,microvascular insufficiency and autoimmune damage to nervefibers (40).

It has been also reported that abnormalities in diabetic neu-ropathy include axonal degeneration in nerve fibers and pri-mary demyelination resulting from Schwann cell dysfunction

(41). Suzuki et al. (42) reported that sorbitol itself and second-ary sodium accumulation caused by an increase in sorbitolmay have been major contributors to the increase in intracellu-lar hydration in a hydrogen 1 nuclear magnetic resonance

study. It has further been hypothesized that in individuals withdiabetes mellitus, the peripheral nerve is swollen because of in-creased water content related to increased aldose reductase

conversion of glucose to sorbitol (43).

Fig. 3 The median nerve (MN) CSA in a child with DPN: (A) Transverse scan of the median nerve in the wrist showing the neuronal

fascicles and the epineurium. (B) The sonographically measured CSA at the inner border of the perineurium using the manual tracing

technique was 0.103 cm2.

Fig. 4 Linear Regression analysis showing a highly significant

positive correlation between the mean CSA of the median nerve

and the mean median nerve motor latency among children with

DPN(r = 0.735; p= 0).

Fig. 5 ROC curve analysis showing the diagnostic performance

of the mean CSA for discriminating patients without DPN from

control individuals, AUC = 0.814.

Evaluation of median nerve in children with type1 diabetes using ultrasonographic imaging and electrophysiology 569

Although, the symptoms of DPN appear bilaterally from

the soles or feet and the wide use of NCS in the diagnosis ofDPN making NCS in the lower limbs to appear more appro-priate for assessing DPN, we performed NCS in the upper

limbs. This is because NCS in the lower limbs is lengthy andaction potentials in the lower limbs sometimes cannot beevoked in patients with advanced DPN. Moreover, Sasaki

et al. (44) and Kohara et al. (45) reported that motor nerveconduction velocity (MNCV) slowing in the upper limbs wassimilar to that in the lower limbs of diabetic patients. Also,

the skin temperature and humidity easily affect the sensorynerve conduction velocity at the time of measurement, so itis often impossible to measure (36).

Mizumoto et al. (46) chose to look at the distal motor la-tency and MNCV because the sensory nerve conduction veloc-ity was not measurable in many hands and therefore appeared

to be an unsuitable parameter. Thus, we carried out motornerve conduction studies only in the upper limbs. This is alsosustained as small myelinated and unmyelinated nerve fibers,

Fig. 6 ROC curve analysis showing the diagnostic performance

of the mean CSA for discriminating patients with DPN from

control individuals, AUC = 0.844.

570 R. Refaat et al.

which are affected early in the disease course of diabetic neu-ropathy; do not contribute to the sensory action potential de-

tected by routine NCS. The sensory action potential is alteredonly after involvement of larger myelinated fibers, which is of-ten a late event in patients with diabetes (41).

The mean median nerve CSA in our study was significantlylarger in diabetic children without and with DPN comparedwith that of control individuals, but there was no significantdifference between diabetic children without and with DPN.

Alternatively, Watanabe et al. (36) established in their studythat the CSA was significantly larger in patients with DPNthan in the control individuals and patients without DPN.

Our results showed that the increase in the sonographicallymeasured cross-sectional area of the median nerve was accom-panied with diminished MNCV and delayed motor latency.

This finding goes in agreement with the results of the studydone by Watanabe et al. (36). We also coincide with Watanabeet al. (36) who did not only hypothesize that an enlarged med-ian nerve in diabetic patients may occur because of increased

water content but also suggested that the nerve swelling dueto increased water content may partly contribute to slowingof the nerve conduction. Additionally, it was found that there

is slowing of nerve conduction velocity in symptomatic dia-betic neuropathy owing to demyelination and loss of largemyelinated fibers and a decrease in nerve action potentials ow-

ing to loss of axons (47–49).We also found in the group of children without DPN that

the mean median nerve CSA for both wrists had no correlation

with mean median nerve motor latency for both wrists and asignificant negative correlation with mean median nerveMNCV. While, in the group of children with DPN, the meanmedian nerve CSA for both wrists had a highly significant po-

sitive correlation with mean median nerve motor latency forboth wrists and no correlation with mean median MNCV. In-stead of that, Watanabe et al. (36) ascertained through their

study that the CSA had a significant positive correlation withthe motor latency as well as a significant negative correlationwith the MNCV.

In this study, there was significant difference regarding themean median nerve MNCV between control individuals versus

children with DPN, This concurs with Riihimaa et al. (50) whostated that deterioration in nerve segmental myelination andaxonal structure, reflected in decreased nerve conduction

velocity, has been implicated as contributing to the peripheralnerve problems seen in patients with type1 diabetes. Moreover,Dyck (51) declared that accumulation of sorbitol and fructose

generated from glucose shunted into the polyol pathway by al-dose reductase and sorbitol dehydrogenase together with defi-ciencies of myoinositol and diacylglycerol may all combine as

potent metabolic factors for slowed conduction velocity.Even though, we found that there was a non significant dif-

ference between children without DPN and those with DPNregarding the mean value of HbA1c and the duration of diabe-

tes with the values of HbA1c being higher in children withDPN. Conversely, Cenesiz et al. (52) concluded that the dura-tion of disease and impaired glycemic control play an impor-

tant role in the development of neuropathy. This wasaccomplished through the statistically significant relationshipswhich were found between the glycemic control values and the

duration of disease with the median nerve conduction velocity.Also, Lee et al. (53) recognized that the duration of diabetesand poor glycemic control proved to be more important risk

factors over 5 years as related to the development of subclini-cal neuropathy. Moreover, Oguejiofor et al. (54) accomplishedthat diabetic subjects with a long duration of diabetes(>10 years) almost always have associated peripheral neurop-

athy. In view of that, Said (41) stated there is currently noeffective treatment for diabetic neuropathy and good glycemiccontrol is the only way to minimize the risk of occurrence of

neuropathy in patients with diabetes.Finally, we recommend further studies regarding this age

group with a much larger number of diabetic children to con-

firm our findings. Consequently, this will lead to early manage-ment of complications of PN and hence a better way of life.

5. Conclusion

The sonographically measured CSA of the median nerve in thecarpal tunnel of children with DPN is greater than that of

healthy individuals correlating considerably with the mediannerve motor latency and in addition, it has significant positivecorrelation with the duration of diabetes.

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