Evaluation of Nerve Ultrasound in Detecting Clinical and Subclinical Peripheral Neuropathy in Children and Adolescents With Type 1 Diabetes Mellitus

Aim of study:

To evaluate accuracy of nerve ultrasound in detecting clinical and subclinical peripheral neuropathy in children and adolescents diagnosed with type 1 diabetes melitus .

Introduction Type 1 diabetes (T1D) is a chronic disease with long-term vascular complications which include nephropathy, retinopathy, neuropathy, and macrovascular disease . In childhood and adolescence, early functional and structural vascular related abnormalities may be present a few years after the onset of the disease, so In this period intensive education and treatment may prevent or delay the onset and progression of complications.

Diabetic neuropathy (DN) is an important complication in patients with diabetes since it is related to mortality, morbidity, and a decrease in the quality of life ,as it is associated with neuropathic pain, foot ulceration, and subsequently gangrene and amputation.

Typical DPN is a chronic, nerve-length-dependent, distal symmetrical sensorimotor polyneuropathy (DSPN) and is considered as the most common form among diabetic neuropathies .

DPN can be classified into subclinical and clinical stages; based on history with sensory disturbances (possible); symptoms and/or signs of nerve dysfunction (probable); symptoms and/or signs plus abnormal gold standard test (confirmed); abnormal gold standard test (subclinical).

Subclinical neuropathy is defined as asymptomatic peripheral neuropathy, which is one of the common complications of patients with diabetes mellitus (DM). There is considerable uncertainty about the prevalence of diabetic peripheral neuropathy (DPN) in pediatric populations, which is probably due to the lack of large epidemiological studies performed on pediatric patients with DM, who often show few symptoms of neurological involvement.

Evidence from western studies have suggested that a quarter of children and adolescents with type 1 diabetes have clinical or subclinical evidence of nerve injury at diagnosis , The prevalence of peripheral neuropathy in known children with T1DM is reported to be as high as 50% .

Many risk factors have been suggested for peripheral neuropathy, such as the duration of diabetes, age at onset, height, puberty, positive family history, and diabetic complications of puberty .

The effect of chronic hyperglycemia is mediated by the increase of the intracellular level of glucose and sorbitol, which eventually leads to oxidative stress and the generation of free radicals, which damage intracellular macromolecules. In addition, chronic hyperglycemia induces the formation of advanced glycation end products (AGEs), which modify the structure of myelin, leading to axonal degeneration.

Currently, the diagnosis of DPN is mainly based on characteristic symptoms and signs. Nerve conduction studies (NCS) is one of the gold standard techniques for diagnosing DPN . It evaluates the occurrence and development of DPN by detecting the ability of peripheral nerve to transmit electrical signals in patients with DN. NCS has the characteristics of being quantifiable, objective, and sensitive, but it has the following disadvantages: time-consuming, high cost, poor experience, and the need for professional doctors to operate.

Although there are no guidelines on screening subclinical diabetic neuropathy, nerve conduction study (NCS) is the most common tool used for diagnosing it.

The pattern of nerve dysfunction has varied in neurophysiological studies on pediatric populations .Some studies found that subclinical sensory affection is prevalent. And others found that subclinical motor affection more common.

High-resolution ultrasound is of growing importance as a painless method complementary to nerve conduction studies in the workup of disorders of the peripheral nervous system, especially in children and adolescents .Cross-sectional area, echogenicity, morphology of the individual nerve fascicles, thickness of the epineurium, vascularization and mobility of the nerve are the main parameters evaluated with nerve ultrasound in polyneuropathies.

High-frequency ultrasound was first used in the clinical diagnosis of DPN as a supplement to NCS. It measures the size, blood vessels, echo, and mobility of the diseased nerve to show the damage of the nerve tissue, which can effectively improve the diagnostic efficiency of DPN and reduce the missed diagnosis rate and the misdiagnosis rate . In patients with DPN, the cross sectional area (CSA) and longitudinal section of the nerve are increased, and the echogenicity of the nerve, the boundary ambiguity, and the blood flow in the nerve are also significantly increased. The mean CSA in the examined nerves was higher in moderate to severe DPN than the mild DPN .

High resolution ultrasound has unique diagnostic advantages for early or subclinical neuropathy. High-frequency ultrasound can detect subclinical involvement of peripheral nerves and abnormalities in patients with normal electrical diagnosis .

Eligibility Criteria:
Inclusion Criteria:

- 1.Children and adolescents aged 8-17 y diagnosed as type 1 DM according to American diabetes association ( ADA) (17) .

2.On multiple injection or insulin pump for at least 5 years or more. 3.Patients are free from acute complication like diabetes ketoacidosis (DKA), symptomatic hypoglycemia, or infection for at least one month before enrollment in the study.

Exclusion Criteria:

* 1.Age less than 8 years or more than 17 years. 2.Diabetes other than T1DM . 3.Patients with known neuropathy of any other cause rather than diabetes. 4.Diabetic children with thyroid dysfunction ,coelic disease or anemia.