PERIPHERAL NEUROPATHY IN DIABETIC CHILDREN AND ADOLESCENTS

ABSTRACT. In order to establish the general prevalence of peripheral neuropathy in diabetic children and adolescents, median motor and sensory conduction velocities and the peroneal motor conduction velocity were registered in 161 unselected diabetic children and adolescents and 55 healthy controls. The influence of the duration and the balance of diabetes on the results was analysed in the diabetic group. In the controls the age correlated positively with the median motor and sensory conduction velocity, but not with peroneal motor conduction velocity. In diabetic children, the greatest impairment was found in the peroneal motor conduction velocity, 49 patients (30 %) had a value lower than -2SD below the mean normal value. There was a correlation between the balance of diabetes based on HbA₁ and glucosuria, and median and peroneal motor conduction velocities. The median motor conduction velocity was independent of the duration of diabetes, but a correlation was found between the duration of diabetes and peroneal motor conduction velocity impairment. Motor conduction velocity determination of the peroneal nerve can be used both in revealing and following the abnormality in peripheral nervous function in diabetic children. Regular follow-up of nervous function test results may help in assessing the importance of good metabolic control in preventing diabetic complications.     

A 5‐yr follow‐up nerve conduction study for the detection of subclinical diabetic neuropathy in children with newly diagnosed insulin‐dependent diabetes mellitus

Lee S‐S, Han H‐H, Kim H. A 5‐yr follow‐up nerve conduction study for the detection of subclinical diabetic neuropathy in children with newly diagnosed insulin‐dependent diabetes mellitus. Pediatric Diabetes 20XX: 00: 000–000 Objective: To investigate the changes of peripheral nerve conduction in children with insulin‐dependent diabetes mellitus (IDDM) prospectively from diagnosis and to know how those results were related to clinical risk factors. Methods: A total of 37 patients (14 males and 23 females) aged 3–19 yr (mean 12.0 ± 3.7) with newly diagnosed IDDM underwent bilateral nerve conduction studies (NCS) of median, ulnar, posterior tibial, peroneal, and sural nerves annually for 5 yr. Results: In all, 12 patients (32.4%) showed electrophysiological evidence of polyneuropathy in at least two different nerves including the sural nerve at the diagnosis of IDDM; 20 patients (54%) had multiple (≥2) abnormalities in parameters of NCS. The most common abnormal parameters at the diagnosis were conduction velocities of peroneal motor and sural nerves. In sequential NCS over 5 yr, the percentage of abnormal nerve conduction velocities rose except within the sural nerve. Poor metabolic control, height, duration of diabetes, and older age of onset were related to the changes of parameters of NCS over 5 yr. Among those risk factors, the duration of diabetes and sustained hyperglycemia affected the parameters of NCS more frequently than others. Conclusions: Children with IDDM frequently have nerve conduction abnormalities without clinical neuropathy at initial diagnosis. The frequency of abnormalities of any attribute of nerve conduction increased over the 5 yr follow‐up. The duration of diabetes and poor glycemic control proved to be more important risk factors over 5 yr as related to the development of subclinical neuropathy.     

Evaluation of sensorimotor polyneuropathy in children and adolescents with type I diabetes: associations with microalbuminuria and retinopathy

Abstract: To investigate diabetic polyneuropathy, we measured peroneal motor conduction velocity, sural sensory nerve conduction velocity and vibratory sense threshold (biothesiometry) in 28 children and adolescents with insulin-dependent diabetes (type 1), and in 28 age- and sex-matched, normal controls. Age varied from 8 to 19 yr (mean ± SD = 13.04 ± 2.61); age at the onset of diabetes from 9 months to 12 yr (4.53 ± 2.42 yr); and the duration of diabetes from 5 to 16 yr (8.48 ± 2.98). Eight patients (28%) fulfilled the minimal criteria for the diagnosis of polyneuropathy. Four of these patients showed symptoms while three had clinical signs of neuropathy. Eight patients had abnormal, sural sensory nerve conduction velocities. The presence of polyneuropathy did not correlate with the duration of diabetes or degree of metabolic control of diabetes. The prevalence of microvascular complications (microalbuminuria and retinopathy) was 32%. The presence of microvascular complications did not correlate with metabolic control but did with the duration of diabetes. The relationship between polyneuropathy and microvascular complications was 34%.     

Peroneal motor nerve conduction velocity in diabetic children and adolescents

To investigate incipient diabetic neuropathy, peroneal motor nerve conduction velocity (PMNCV) was measured in 61 diabetic children and adolescents whose type 1 diabetes became clinically apparent before the age of 14 years. PMNCV in diabetic patients (48.3±5.6m/s) was significantly lower than in controls (56.5±5.5 m/s), 23 diabetics (36%) having a value more than 2 SD below the mean for normals. There was a highly significant negative correlation between PMNCV and HbA₁ levels concomitant with PMNCV measurement or mean annual HbA₁ concentrations preceding PMNCV. The relationship between PMNCV and the clinical score of diabetic control since the onset of the disease was also significant. Age, duration of diabetes and HLR-DR antigens were unrelated to PMNCV. EEG abnormalities and retinopathy, whose pathogenesis is different, were not necessarily associated with subclinical neuropathy. Being easy and sensitive, PMNCV determination provides the paediatric diabetologist and the patient himself with an important motivation to improve diabetic control.Abbreviations PMNCV peroneal motor nerve conduction velocity Partly presented at the 6th International Beilinson Symposium on Future Trends in Juvenile Diabetes, held in Israel, October 1984     

Nerve conduction in children suffering Insulin Dependent Diabetes Mellitus

Objective: To determine the incidence of peripheral neuropathy in children suffering Insulin Dependent Diabetes Mellitus (IDDM) as well as to determine the relationship between other criteria of the disease and neuropathy.Methods : 40 children (17 males, mean age 11.9 years) suffering IDDM and receiving insulin therapy involving two injections a day and 30 healthy children (17 males, mean age 11.7 years) were included in the study. They were inquired about their demographical characteristics as well as the presence of neurological symptoms. Their detailed neurological examinations were conducted. Their glycemic control values (Hb A¹C) were recorded, and their nerve conduction studies were performed from right upper and lower extremities.Results : All nerve conduction values of children with IDDM were found to be significantly lower (p <0.0001) as compared to the control group. 60% of diabetic children (n=24) were found to suffer peripheral neuropathy. Statistically significant relationships were found between the glycemic control values and the peroneal, sural, tibial, ulnar and median nerve conduction velocities, and also between the duration of disease and the peroneal, sural, tibial and median nerve conduction velocities.Conclusion : The peripheral neuropathy is rather a frequently observed complication in diabetic children. The duration of disease and impaired glycemic control play an important role in the development of neuropathy. The introduction of new methods designed to ensure better glycemic control will reduce the incidence of the complication.     

Early diabetic complications in a population of young patients with type 1 diabetes mellitus despite intensive treatment

AIM: To describe the prevalence of early complications in an unselected population of patients with type 1 diabetes mellitus (DM1) diagnosed in childhood with intensive insulin treatment from diagnosis. METHODS: Eighty children and adolescents with DM1, age 7-22 years and DM1 duration >3 years, were studied. Neuropathy was defined as abnormal nerve conduction finding in > or = 2 of 4 nerves (sural and peroneal nerves), nephropathy as albumin excretion rate > or = 20 microg/min and retinopathy as all grades of retinal changes in fundus photographs. RESULTS: The prevalence of neuropathy was 59%, of retinopathy 27% and of nephropathy 5% after 13 years DM1 duration. Mean (SD) long-term HbA1c was 8.4 (0.9)% (DCCT-corrected value). CONCLUSION: Even in a population with intensive insulin treatment from the beginning and fairly good metabolic control, the prevalence of subclinical neuropathy was high, while other diabetic complications were lower than usually reported.     

小儿运动神经传导正常值及发育规律

研究目的探讨小儿运动神经传导正常值及发育规律。研究方法１４９名０－１４岁儿童按年龄分为７组，成人组共１９人，年龄（２０－３５）岁。用神经诱发电位仪测量各受试者正中神经，尺神经，胫神经和腓神经的运动传导功能。结果６岁前神经动作电痊潜伏期随年龄增大而缩短，６岁后又渐延长，新生儿尺神经传导速度最快，其次为腓神经和正中神经，最慢为胫神经。出生后３个月，正中神经发育首先加快，３岁接近尺神经。胫神经于３个月－     

Nerve conduction and autonomic nerve function in diabetic children. A 10-year follow-up study

In order to study the long-term development of diabetic neuropathy in children with newly diagnosed diabetes mellitus, 144 children were entered in a prospective study of nerve conduction and autonomic nervous function. Neurophysiological recordings of nerve conduction and parasympathetic function (R-R variations) were made at onset of diabetes and after 2, 5 and 10 years. Low sensory nerve conduction and autonomic dysfunction were found in approximately 25% of the children at onset of diabetes when the patients were not yet in complete remission. During years 0–2, an initial improvement of sensory conduction velocities was found. After 2 years, deteriorations in sensory and motor nerve conduction and autonomic nerve function were common and further deterioration was seen over time. A correlation was found between nerve conduction and glycaemic control.     

SENSORY NERVE CONDUCTION VELOCITY AND VIBRATORY SENSIBILITY IN JUVENILE DIABETICS

ABSTRACT. Ludvigsson, J., Johannesson, G., Heding, L., Häger, A. and Larsson, Y. (Departments of Paediatrics and Neurophysiology, University Hospital Linköping, Sweden and Novo Research Institute, Bagsvaerd, Denmark). Sensory nerve conduction velocity and vibratory sensibility in juvenile diabetics. Relationship to endogenous insulin. Acta Paediatr Scand, 68: 739, 1979.—Sensory nerve conduction velocity (NCV) and the vibratory sense (biothesiometry) were determined in 67 children and adolescents with insulin dependent diabetes. Age at onset of diabetes varied between 1–14 years (mean ±S.D. 6.5±3.6) and the duration of diabetes between 4–17 years (7.7±3.4). Within ±3 months of the nerve function tests blood was drawn for determination of C-peptide and insulin antibodies (IgG and IRI). A low NCV (<50 m/s) in the sural nerve and/or an abnormal vibratory sense (≥1.0 microns) were found in 34 patients (50.7%). Measurable fasting serum C-peptide 0.04–0.60 pmol/ml (0.17±0.15) was found in 16 patients (23.9%). All but one patients had insulin antibodies with IgG 0.130–11.029 mU/ml (2.957±2.509) and total IRI 10–9120 μU/ml (1204±1723). In multiple regression analysis we did not find any correlation between nerve function and sex, age, or age at onset of diabetes, and there was only a weak relationship between NCV and duration. However, there was a positive correlation between NCV and C-peptide (p<0.001). Vibration sense was also better among patients with C-peptide (p<0.05). The results support the view that insulin deficiency contributes to peripheral diabetic neuropathy.     

Sensory nerve conduction velocity and vibratory sensibility in juvenile diabetics. Relationship to endogenous insulin

Sensory nerve conduction velocity (NCV) and the vibratory sense (biothesiometry) were determined in 67 children and adolescents with insulin dependent diabetes. Age at onset of diabetes varied between 1-14 years (mean +/- S.D. 6.5 +/- 3.6) and the duration of diabetes between 4-17 years (7.7 +/- 3.4). Within +/- 3 months of the nerve function tests blood was drawn for determination of C-peptide and insulin antibodies (IgG and IRI). A low NCV (less than 50 m/s) in the sural nerve and/or an abnormal vibratory sense (greater than or equal to 1.0 microns) were found in 34 patients (50.7%). Measurable fasting serum C-peptide 0.04-0.60 pmol/ml (0.17 +/- 0.15) was found in 16 patients (23.9%). All but one patients had insulin antibodies with IgG 0.130-11.029 mU/ml (2.957 +/- 2.509) and total IRI 10-9120 muU/ml (1204 +/- 1723). In multiple regression analysis we did not find any correlation between nerve function and sex, age, or age at onset of diabetes, and there was only a weak relationship between NCV and duration. However, there was a positive correlation between NCV and C-peptide (p less than 0.001). Vibration sense was also better among patients with C-peptide (p less than 0.05). The results support the view that insulin deficiency contributes to peripheral diabetic neuropathy.     

Screening for subclinical complications in young type 1 diabetic patients: experience acquired in Brussels

Clinical studies conducted since the 1970s by the pediatric diabetology group of the Free University of Brussels have demonstrated that screening for subclinical retinopathy, neuropathy and nephropathy should be started at puberty and at least 3 years after the diabetes diagnosis. The goal is to detect early abnormalities responsible for subclinical disorders that can be reversed by improved metabolic control, thus preventing the occurrence of irreversible potentially incapacitating lesions. A 1974 retinal fluorescein angiography study showed that the development of microaneurysms, which are irreversible lesions, could be preceded by fluorescein leakage due to disruption of the blood-retinal barrier. Risk factors for early retinopathy include: duration of diabetes, age at diagnosis (with younger children having longer times to retinopathy), puberty and sex (with onset one year earlier in girls than in boys), long-term bad metabolic control over several years, high cholesterol levels and excessive body mass index (BMI). On the other hand, rapid improvement of diabetic control may worsen diabetic retinopathy (1985). Minimal EEG abnormalities were found in relationship to frequent and severe hypoglycemic comas and/or convulsions and retinopathy (1979). Desynchronization of action potentials in distal nerve fibers preceded conduction velocity slowing (1981). A single high glycated hemoglobin value was associated with peroneal motor nerve conduction slowing (1985), which was not observed in the femoral nerve (1987). Sympathetic skin response (1996) and statistical analysis of heart rate variability (2001) could have some interest for the diagnosis of early diabetic autonomic neuropathy. Early microproteinuria is of mixed origin, being both glomerular (microalbumin) and tubular (Beta2-microglobulin). Exercise testing to exhaustion did not provide additional information than the basal excretion (1976). Microtransferrinuria (1984) and urinary acid glycosaminoglycans output (2001) could also be predictive markers of glomerular dysfunction. Physical training reduced exercise-related proteinuria by half (1988). High levels of serum lipoprotein (a) were not associated with the presence of subclinical complications (1996). On the other hand, ultra sensitive C-reactive protein could be an interesting indicator for the risk of developing early complications (2002). Poor metabolic control was associated with higher levels of triglycerides, total cholesterol, LDL cholesterol and apolipoprotein B (1990). Decreased gluthatione peroxidase, gluthatione reductase and of vitamin C levels, denoting moderate oxidative stress, were found (1996), although there was no evidence of increased LDL cholesterol peroxidation (1998). Erythrocytes exhibited increased glycolytic activity and neutrophils decreased migration in relationship with metabolic control (1992). The degree of metabolic control influenced serum triiodothyronine levels (1985), magnesium concentrations (1999) and infection by Helicobacter Pylori (1997). Insulin therapy could activate the complement pathway if intermediate and long-acting insulin preparations without protamine sulphate are used (1992) and provoke higher BMI in adolescents on 4 insulin injections (1988). Well-being was inversely related to glycated hemoglobin levels (1997).     

Real-time sonography for screening of gallbladder dysfunction in children with type 1 diabetes mellitus

The aim of this study was to evaluate the occurrence of gallbladder dysfunction in children with type 1 diabetes mellitus using real-time ultrasonography. The study population consisted of 20 diabetic children (11 male, 9 female; age 11.7+/-2.8 years; diabetes duration 0.5-7 years) with clinically negative neuropathy findings and 15 healthy controls (11 male, 4 female; age 10.5+/-3.7 years). Three-dimensional measurements of the gallbladder were made before and 15, 30, 45, 60 min after intake of diet chocolate. Gallbladder volumes were calculated by the ellipsoid formula. Fasting gallbladder volume of diabetic children (16.9+/-9.5 ml) was significantly greater than that of the controls (10.6+/-5.3 ml; p=0.017). Ejection fraction and maximal contraction showed no significant difference between the two groups. Diabetic patients with multiple microvascular complications had diminished gallbladder motility. There was a negative correlation between BMI and maximal contraction (p<0.05). Nerve conduction velocity was diminished in 45% of the diabetic patients. In conclusion, gallbladder function is preserved in pediatric type 1 diabetic patients with a disease duration less then 10 years, but dilated gallbladder at rest may be an early sign of gastrointestinal autonomic neuropathy and a risk factor for gallstone formation.     

MOTOR CONDUCTION VELOCITIES IN NEWBORN INFANTS OF VARIOUS GESTATIONAL AGES

The motor conduction velocities, in the ulnar and peroneal nerves of newborn infants, of various postmenstrual ages were studied. It was found that: 1. The conduction velocities, in children of a short gestational age is significantly lower than those of fullterm infants. 2. The conduction velocities, of the peroneal nerve, is slightly but significantly lower than those of the ulnar nerve, in both groups of children. It is also concluded that the determination of motor conduction velocities seems to be an additional method, of value, in assessing the degree of maturity at birth, and in determining the gestational age.     

Peripheral nerve conduction abnormalities in children exposed to alcohol in utero

OBJECTIVE: We performed a longitudinal study of nerve conduction velocity to determine the effect of prenatal alcohol exposure on the peripheral nervous system.Study design We studied 17 children exposed to >2 oz of absolute alcohol/day prenatally and 13 unexposed children, identified prospectively from a cohort of pregnant women screened during prenatal care. Nerve conduction assessment was done on the median, ulnar, peroneal and tibial nerves during the newborn period and between 12 and 14 months of age. RESULTS: At both assessments the alcohol-exposed subjects had significantly slower ulnar motor nerve velocity (P=.007), smaller proximal (P=.018) and distal amplitude (P=.051). They also showed reduced tibial nerve velocity (P=.06) and a decrease in distal amplitude. CONCLUSIONS: This study demonstrates that prenatal alcohol exposure is associated with abnormalities in nerve electrical properties, and that the pattern is different from that seen in adults. Electrophysiologic abnormalities in peripheral nerves should be added to the problems found in children of alcohol abusing mothers.     

Pupil size in diabetes.

Sympathetic function was studied in 101 diabetic children and 102 age and sex matched control children, as part of a longitudinal study of the evolution of microvascular disease in the population of diabetic children and adolescents in Avon County. The median (range) age of the diabetic population was 13.5 (6.0-17.2) years, the duration of diabetes was 4.0 (0.4-13.9) years, and glycated haemoglobin (HbA1) was 10.9 (7.0-18.1)%. Pupillary adaptation in darkness, as an index of sympathetic neuropathy, was measured using a Polaroid portable pupillometer. Diabetic children had a significantly smaller median pupillary diameter, measured as the pupil/iris ratio and expressed as a percentage, than control children (median (range) 62.9 (50.3-72.1) v 65.9 (52.2-73.8)). Pupillary diameter was significantly related to diabetes duration (r = -0.22), HbA1 (r = -0.34), systolic blood pressure (r = -0.25), diastolic blood pressure (r = -0.49), and mean albumin/creatinine ratio on random urine samples (r = -0.26). Pupillary diameter was not related to age (r = -0.1). Eight (7.9%) diabetic and four (3.9%) control children were identified as having abnormal pupillary dilation in darkness. In comparison with the rest of the diabetic population, these diabetic children had longer diabetes duration and poorer glycaemic control. Polaroid pupillometry has demonstrated subclinical autonomic neuropathy in a population of diabetic children and adolescents. These abnormalities were related to poor metabolic control, long diabetes duration, and also to other indices of microvascular disease.     

Adolescence peroneal neuropathy associated with rapid marked weight reduction: case report and literature review.

PURPOSE: We report herein an uncommon presentation of peroneal nerve palsy and possible myelopathy in an adolescent associated with marked uncontrolled weight loss during a relatively short period. CASE PRESENTATION: He presented with left drop foot accompanied with sensory impairment at the foot dorsum. Neurophysiologic studies revealed a severe neuropathy of the left peroneal nerve with evidence of a conduction block at the left fibular head suggestive of entrapment neuropathy. ETIOLOGY: As for the underlying etiology of acute peroneal neuropathy (PN) and possible myelopathy associated with marked weight loss, it has been suggested that rapid loss of the subcutaneous tissue may lead to entrapment of the peroneal nerve at the fibular head leading to foot drop. Body fat percentage was found remarkably low for age at 10% (normal value for age for males: 22.3%) indicative of massive rapid weight reduction markedly depleting fat stores. CONCLUSION: When an adolescent presents with acute foot drop, PN associated with rapid uncontrolled weight reduction should be taken into account. Prompt resumption of a balanced diet including vital nutritional ingredients may avoid permanent neurological damage and probably assist in recovery from severe flaccid weakness of the lower extremity.     

Microangiopathy in Singapore diabetic children

Nineteen children with insulin-dependent diabetes mellitus were assessed for microangiopathic complications in the University Department of Paediatrics, Singapore. Of 17 who underwent nerve conduction studies, all showed impaired nerve conduction velocities, with more sensory than motor nerve involvement. The extent of neuropathy was significantly correlated with the duration of disease. Of five children who showed significant proteinuria, two had impaired creatinine clearance, two had cataract formation, and two retinopathy, in one background and in one proliferative. Our study showed a high prevalence of microangiopathic complications in these diabetic children and it is hoped that improved blood glucose control, with the aid of home blood glucose monitoring, may minimize or arrest the microangiopathic complications.     

Reversal of iron deficiency anemia-induced peripheral neuropathy by iron treatment in children with iron deficiency anemia

The effects of iron deficiency anemia (IDA) on nerve conduction and efficiency of iron therapy were investigated by peripheral nerve-electrophysiological measurements. Eighteen children (10 boys, eight girls; mean age 31 +/- 1.3 months) with IDA and 12 healthy children (six boys, six girls; mean age 29 +/- 1.3 months) were enrolled into the study. Nerve conduction velocity was measured in the median and posterior tibial nerve. After nerve conduction values were determined in the patients and controls, 6 mg/kg/24 h ferrous sulphate was given orally to the patients for 3 months and nerve conduction velocity tests were performed again. Median/motor and sensory nerve conduction velocity and tibial/motor nerve distal-amplitute values of children with IDA were lower than for the control group (p < 0.05, p < 0.01 and p < 0.001 respectively). With iron supplementation these values increased to the normal levels and even higher than control levels for some parameters. In correlation studies between whole blood parameters and nerve conduction velocity results, there was a correlation between median/sensory nerve conduction velocity values and serum iron levels. Additionally there was a correlation between some nerve conduction velocity values and age. In conclusion, the evidence from this preliminary study suggests that peripheral neuropathy may develop in children with IDA. Peripheral neuropathy symptoms in these patients may be improved by iron therapy.     

Slow Nerve Conduction Velocity in Cretins

The ulnar and posterior tibial conduction velocities were measured in 6 untreated and 3 treated cretins. In 4 of the untreated patients, the conduction velocity of both nerves was slower than normal; in 1 patient the ulnar and in the other the posterior tibial nerve conduction velocity was slower than normal. There was a close agreement between bone age and the age corresponding to the slow conduction velocities. The 3 treated cretins all had normal posterior tibial conduction velocities, while the ulnar conduction velocity was normal in one, slower in another, and faster than normal in the third.The slow nerve conduction velocity in cretins probably reflects a delay in maturation of the peripheral nerves. Nerve conduction velocity measurement may be a useful screening test in suspected congenital hypothyroidism, and may also prove of value in assessing response to therapy.     

Early Diagnosis of So-Called Late Complications in Type 1 Diabetic Children

Prevention of late complications is the main problem in type 1 diabetes of childhood. Longitudinal studies of subjects diagnosed before puberty demonstrated significant prevalence of retinopathy, nephropathy and neuropathy after 10- 15 years, correlated with the duration of diabetes. Proliferative retinopathy is rarely observed in children with diabetes of less than 5 years duration but vitreous fluorophotometry has shown abnormalities of retinal vessels in asymptomatic patients. In early diabetes glomerular permeability can be tested by radioimmunoassay of microalbuminuria; values above 30 mcg/min are a good predictor of later clinical proteinuria. The development of overt neuropathy is extremely variable and it may not be present even after many years of poorly controlled diabetes. Vitreous fluorophotometric abnormalities, basal and post-exercise microalbuminuria and reduction of nerve conduction velocity have been proven to be reversible with intensive therapy. When secalled “late” complications are diagnosed early, careful and intensive therapy to maintain metabolic equilibrium near normal is called for.