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Objective To investigate the optimal sonographic method for diagnosing carpal tunnel syndrome (CTS) in patients with diabetic sensorimotor polyneuropathy (DSP). Methods A total of 190 participants were divided into four groups based on DSP history and electrodiagnostic results of CTS. The absolute parameters were measured at baseline and the relative values were calculated: maximal cross-sectional area (CSA) of the median nerve throughout the carpal tunnel (Mmax), median nerve CSA at the forearm level (Mf), ulnar nerve CSA at the pisiform level (Upi), difference between Mmax and Mf (DMM), and difference between Mmax and Upi (DMU). Then, the optimal ultrasonographic parameters for diagnosing CTS, according to the presence of DSP, using absolute and relative cutoff values were analyzed. Results Median and ulnar nerve CSAs were significantly larger in the DSP group than in the control group. In the DSP participants, the mean Mmax, DMM, and DMU values were significantly larger in patients with both DSP and CTS than in patients with DSP only. The Mmax thresholds of 9.5 mm2 in the control group and 11.5 mm2 in the DSP group showed the greatest sensitivity and specificity for diagnosing CTS. The DMM thresholds of 2.5 mm2 and DMU thresholds of 4.5 mm2 had the greatest sensitivity and specificity in both the DSP and control groups. Conclusion Measurement of Mmax, DMM and DMU is an optimal ultrasonographic evaluation method for diagnosing CTS in patients with DSP.

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