Diabetic Peripheral Neuropathy Diagnosis Using Nerve Ultrasonography
The conventional diagnostic modality for diabetic peripheral neuropathy is via the use of nerve conduction studies (NCS), however, this investigation does not evaluate or demonstrate the structure of the nerve. This research was aimed at investigating the use of peripheral nerve ultrasonography as a means to note the presence of peripheral neuropathy and its severity in type 2 diabetics.
This study enrolled a total of 156 patients who underwent peripheral nerve ultrasonography on the distal median nerves and the distal tibial nerves. The Total Neuropathy Score and the Modified Toronto Clinical Neuropathy Scale was used to grade the severity of neuropathy. A single ultrasonographer conducted the ultrasonographic techniques and was not made aware of the nerve conduction studies results to avoid bias.
With increasing total neuropathy scores and each Modified Toronto Clinical Neuropathy Scale quartile, a stepwise rise was observed in the tibial nerve cross-sectional area. An association was noted between the tibial nerve cross-sectional area and the severity of neuropathy in a regression analysis. The tibial nerve elicited an 85.7% specificity and a 70.5% sensitivity in the diagnosis of peripheral neuropathy on a receiver operator curve analysis. Tibial nerve cross-sectional area on a binary logistic regression analysis was shown to be a predictor of abnormal neuropathy score and abnormal action potential amplitude of the sural nerve. The tibial nerve ultrasonography investigational modality was observed to have good specificity and sensitivity in the diagnosis of peripheral neuropathy associated with type 2 diabetics. The tibial nerve cross-sectional area was demonstrated in this study to be associated with the severity of neuropathy. Serial investigational studies in the future which involve the use of nerve conduction studies and nerve ultrasound may be beneficial in determining if variations seen on nerve ultrasound occur before the development of neuropathic symptoms or abnormalities in nerve conduction.
A minimum of 50% of patients with type 2 diabetes suffer from diabetic peripheral neuropathy. Type 2 diabetic patients who suffer from diabetic neuropathy have a common presentation of generalized distal symmetric polyneuropathy, which usually occurs with neuropathy of the feet.
The risk of symptomatic neuropathy is raised by clinical conditions like obesity, hypercholesterolemia, hypertriglyceridemia, increased waist circumference and hypertension
The conventional diagnostic modality for peripheral neuropathy is the nerve conduction study which is not sensitive to early alterations to nerve function and structure.
The role of peripheral nerve ultrasonography is enhanced in the assessment of peripheral nerve disorders in mononeuropathies and polyneuropathies. Ultrasound abnormalities were demonstrated among type 2 diabetics compared to healthy controls in previous studies. This study, however, was carried out to note if the evaluation of nerve structure using nerve ultrasound carried out once at the point of care could accurately diagnose the presence of peripheral neuropathy and its severity in type 2 diabetics. An additional aim of this study was to evaluate the ability of nerve ultrasonography to detect morphological nerve changes in type 2 diabetic patients who are asymptomatic or do not show abnormalities on nerve conduction studies.
The diagnostic accuracy of the diagnosis of tibial nerve peripheral neuropathy was evaluated using the Standards for Reporting of Diagnostic Accuracy Initiative (STARD) criteria. 156 patients with established type 2 diabetes mellitus were enrolled into this study from the Prince of Wales Hospital Diabetes Center in Sydney from August 2020 to June 2021. The Committee of Human Research Ethics in the University of New South Wales gave approval for this study. All investigational procedures and assessments were carried out at the point of care after obtaining informed consent. All included patients were clinically evaluated for peripheral neuropathy with the addition of nerve ultrasonography and nerve conduction studies of tibial and median nerves. The ultrasonographer was not made aware of the patient’s previous nerve conduction studies results to prevent bias. The ultrasonographer, however, was made aware of the patient’s neuropathic signs and symptoms. The Modified Toronto clinical neuropathy scale and total neuropathy score was used to assess peripheral neuropathy.
The total neuropathy score has 8 parts which include vibration sense using a 128-Hz tuning fork, motor and sensory symptoms, pinprick sensation, deep tendon reflexes, motor amplitude of the tibial nerve on nerve conduction studies, the amplitude of the sural sensory nerve on nerve conduction studies and strength examination. Each part of the total neuropathy score gives a maximum point of 4 with a maximum total neuropathy score of 32. A higher total neuropathy score translated to increased severity of peripheral neuropathy. The total neuropathy score can be categorized into 4 grades namely: Grade 0 = TNS score of 0-1, Grade 1 = TNS score of 2-8, Grade 2 = TNS score of 9-16, Grade 3 = TNS score of 17-24 and Grade 4 = TNS score of 25-32.
The Modified Toronto Clinical Neuropathy Scale consists of 6 symptom sections and 5 sensory examination sections. Each section has a score ranging from 0 to 3 with a maximum score of 33. Higher Modified Toronto clinical neuropathy scale scores translated to increased severity of peripheral neuropathy. The symptoms section include numbness, foot pain, weakness, tingling, upper limb symptoms and ataxia. The sensory examination section includes temperature, vibrations, pinprick, light touch and position sense. A single ultrasonographer carried out a standardized nerve ultrasound of the tibial and median nerves. A 10-18 MHz linear array transducer was used to perform imaging. All ultrasound settings were constantly maintained during patient evaluations.
Three hyperechoic rim inner margin’s free hand traces were used to measure peripheral nerve cross sectional area. The cross sectional areas of the tibial nerve was evaluated 5 cm above the medial malleolus, well away from possible sites of entrapment. The nerve was traced alongside tibial vessels above the medial malleolus. The cross sectional area of the median nerve was evaluated above the wrist, one third of the forearm length.
Initially the median nerve was spotted at the inlet of the carpal tunnel, and then traced between the flexor digitorum profundus and flexor digitorum superficialis muscles.
Patients who were less than 18 years of age were excluded from the study. Additionally, patients who were not able to give informed consent, patients who have had a lower limb amputation procedure and patients with peripheral neuropathy caused by other conditions such as alcohol, neurotoxic drugs and vitamin B12 deficiency were excluded from the study.
SPSS Statistics was used to analyze data for variables. A coded system was used to identify patients and analyze important variables. Shapiro-Wilk test was used to determine the normality of the study data. Independent t-tests were used to evaluate normally distributed data. Spearman coefficient (rho) was used in ultrasound and clinical values for correlation studies.
156 type 2 diabetics were enrolled for the study and evaluated. A diagnosis of type 2 diabetes was established in all participants with a mean diabetes duration of 177 months. According to the total neuropathy score and Modified Toronto Clinical Neuropathy Scale, the majority of the patients were seen to have a mild to moderate peripheral neuropathy severity. 19.9% (31 out of 156 patients) of the participants had a total neuropathy score grade 0, 50% (78 out of 156 patients) of participants had a total neuropathy score grade 1, 23.1% (36 out of 156 patients) of participants had a total neuropathy score grade 2, 7.1% (11 out of 156 patients) of participants had a total neuropathy score grade 3. Patient’s age and disease duration were seen in previous studies to be associated with higher severity of peripheral neuropathy, while waist circumference and body mass index were seen to be the same, and not associated with increasing severity of peripheral neuropathy.
All investigational modalities were timed, and nerve ultrasonography of the median and tibial nerves was carried out at a mean time duration of 4.7 minutes. This time duration includes positioning of the patient, tracing of the nerve, capture of image and nerve size calculation.
The mean cross sectional area of the tibia was noted to be raised among a cohort of people with diabetes, with a mean cross sectional area of 14.88 mm2 (normal reference range is 12.4 mm2).
In this study, 65.4% of participants had a tibial nerve cross sectional area of >12.4 mm2. The link between the tibial cross sectional area and rising severity of peripheral neuropathy was investigated by carrying out a subanalysis.
40.4% (63 out of 156 patients) of participants who had deranged nerve conduction studies results were seen to have a mean tibial nerve cross sectional area of 17.91 mm2. 59.6% (93 out of 156) of patients who had normal nerve conduction studies results were seen to have a lower mean tibial nerve cross sectional area compared with those who have abnormal nerve conduction studies report. 48 (51.6%) out of the 93 patients with normal nerve conduction had abnormal tibial nerve cross sectional area, of which, 44.9% showed symptoms of peripheral neuropathy in spite of a normal nerve conduction report.
A higher cross sectional area of the tibial nerve was seen to be linked to higher Modified Toronto Clinical Neuropathy Scale score, which translates to more severe peripheral neuropathy. This correlation was irrespective of age, body mass index, waist circumference, glycated hemoglobin levels and disease duration.
This study was aimed at demonstrating the efficacy of peripheral nerve ultrasound carried out once in the diagnosis of type 2 diabetic peripheral neuropathy. Peripheral nerve ultrasound may be a very beneficial tool in the early diagnosis of peripheral neuropathy and severity assessment prior to the onset of symptoms and alterations in nerve conduction studies.
Owing to its non-invasive technique and efficiency in diagnosis of peripheral neuropathy, nerve ultrasound may have a role in the clinical assessment of diabetic patients in community-based peripheral neuropathy studies and recruitment for clinical trials.
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