Functional bladder disorders encompass a range of distinct conditions characterized by overlapping symptoms of frequency and urgency, which present significant diagnostic challenges. This study aimed to evaluate autonomic function across various functional bladder disorders—specifically detrusor overactivity (DO), hypersensitive bladder (HSB), and interstitial cystitis/bladder pain syndrome (IC/BPS)—utilizing our novel non-invasive neuECG method [1, 2]. We sought to determine whether autonomic parameters could effectively differentiate these disorders.

In this prospective study, we enrolled 107 female participants presenting with symptoms of frequency and urgency, excluding those diagnosed with urinary tract infections. Autonomic function was assessed prior to diagnosis and treatment initiation using neuECG, a technique that simultaneously analyzes skin sympathetic nerve activity (SKNA) and heart rate variability (HRV). Diagnoses of DO and HSB were confirmed through urodynamic studies, while IC was diagnosed based on findings from cystoscopic hydrodistension.

The cohort comprised 32 participants with DO, 23 with HSB, and 52 with IC/BPS. Results indicated that DO exhibited significantly higher SKNA values (1.28 ± 0.38) during the stress phase compared to IC/BPS (1.10 ± 0.29) (p=0.048). Additionally, HSB displayed a significantly higher stress-to-baseline phase ratio of SKNA (1.31 ± 0.34) and a significantly elevated baseline LF/HF ratio (1.23 ± 1.04) in comparison to IC/BPS (0.98 ± 0.38; baseline LF/HF: 0.78 ± 0.53) (p=0.002 and 0.016, respectively). Notably, the stress-to-baseline phase ratio of SKNA demonstrated a superior area under the receiver operating characteristic curve (AUROC) for distinguishing between HSB and IC (AUROC = 0.755) as well as between DO and HSB (AUROC = 0.711), surpassing traditional HRV metrics (see Figure 1).

The significant differences in SKNA values and the stress-to-baseline phase ratio suggest that autonomic parameters derived from the neuECG are effective in differentiating between DO, HSB, and IC/BPS. The findings highlight the potential for the stress-to-baseline phase ratio of SKNA to serve as a reliable non-invasive marker for identifying and distinguishing these bladder disorders.

The results of this study indicate that the stress-to-baseline phase ratio of SKNA is a promising non-invasive autonomic parameter for differentiating HSB from IC, as well as distinguishing DO from HSB. This advancement could significantly enhance diagnostic accuracy for women experiencing frequency and urgency syndromes and offers valuable insights into the underlying mechanisms of these disorders.

Chen YC, Chen HW, Huang TC, Chu TY, Juan YS, Long CY, Lee HY, Huang SP, Liu YP, Chen CJ, Wu MN, Chueh KS, Li CC, Lee CH, Tsai WC, Wu WJ. Skin sympathetic nerve activity as a potential biomarker for overactive bladder. World J Urol. 2023 May;41(5):1373-1379.
Chen YC, Chen HW, Huang TC, Lee CH, Chu TY, Juan YS, Liu YP, Tsai WC, Wu WJ. Higher skin sympathetic nerve activity as a potential predictor of overactive bladder in females refractory to oral monotherapy. Kaohsiung J Med Sci. 2024 Nov;40(11):1020-1028.