Changes in pelvic floor electrical activity and vulvar pain after botulinum toxin treatment of vestibulodynia: are clinical and electrophysiological outcomes related?

Vestibulodynia is a gynecological condition with different treatment options available, including botulinum neurotoxin type A (BoNT/A) injections into the vulvar vestibule. Unlike other treatments, no studies have assessed changes in the myoelectrical activity of the pelvic floor muscles (PFM) after BoNT/A treatment. The aim of this study was thus to evaluate these changes and to correlate them with changes in vulvar pain sensitivity. To do this, 35 patients with vestibulodynia were recruited, the myoelectrical activity of their left and right PFM was recorded with surface electromyography (sEMG), and their vulvar pain sensitivity was monitored according to Visual Analogue Scale (VAS) and an algometer, both before and after BoNT/A treatment. According to our results, patients' signals during PFM relaxation showed a significantly higher power than those of healthy women at baseline, as shown by their root mean square values (RMS), but became similar at follow-up. Patients' mean vulvar pain VAS scores significantly decreased after treatment. Furthermore, baseline-to-follow-up differences of RMS at PFM rest vs. mean VAS were significantly correlated (CC=0.48, p<0.01) so that higher reductions in the PFM activity power were associated with higher decreases in vulvar pain.Clinical Relevance- Altered PFM electrophysiological condition of patients with vestibulodynia becomes similar to healthy women's after BoNT/A treatment. This study also points to a relationship between the evolution of clinical and PFM electrophysiological conditions.

Treatment of Vestibulodynia with Submucosal Injections of IncobotulinumtoxinA into Targeted Painful Points: An Open-Label Exploratory Study.

The studies carried out to date on vulvodynia treatment with botulinum neurotoxin type A (BoNT/A) have followed generic injection protocols and reported contradictory outcomes on its effects. The aim of the present study was thus to propose a protocol for injecting BoNT/A into targeted painful points, to comprehensively assess the clinical effect of BoNT/A treatment and identify the risk/protective factors for successful treatment. Thirty-five vestibulodynia patients were treated with submucosal injections of incobotulinumtoxinA and assessed 8, 12 and 24 weeks after their treatment. Their clinical and pelvic statuses were assessed from self-reported questionnaires (Visual Analogue Scale (VAS), Female Sexual Function Index (FSFI), Marinoff's Dyspareunia Scale (MDS), Hospital Anxiety and Depression Scale (HADS), Catastrophizing Scale (CS)), physical examinations and surface electromyography (sEMG). The patients reported a reduction in provoked vestibulodynia (FSFI, p < 0.01;

Outperformance of interleukin-6 over placental alpha microglobulin-1 in predicting preterm delivery in symptomatic women.

BACKGROUND: Threatened preterm labor is the major cause of hospital admission during the second half of pregnancy. An early diagnosis is crucial for adopting pharmacologic measures to reduce perinatal mortality and morbidity. Current diagnostic criteria are based on symptoms and short cervical length. However, there is a high false-positive rate when using these criteria, which implies overtreatment, causing unnecessary side effects and an avoidable economic burden. OBJECTIVE: This study aimed to compare the use of placental alpha microglobulin-1 and interleukin-6 as vaginal biomarkers combined with cervical length and other maternal characteristics to improve the prediction of preterm delivery in symptomatic women. STUDY DESIGN: A prospective observational study was conducted in women with singleton pregnancies complicated by threatened preterm labor with intact membranes at 24+0 to 34+6 weeks of gestation. A total of 136 women were included in this study. Vaginal fluid was collected with a swab for placental alpha microglobulin-1 determination using the PartoSure test, interleukin-6 was assessed by electrochemiluminescence immunoassay, cervical length was measured by transvaginal ultrasound, and obstetrical variables and newborn details were retrieved from clinical records. These characteristics were used to fit univariate binary logistic regression models to predict time to delivery <7 days, time to delivery <14 days, gestational age at delivery ≤34 weeks, and gestational age at delivery ≤37 weeks, and multivariate binary logistic regression models were fitted with imbalanced and balanced data. Performance of models was assessed by their F2-scores and other metrics, and the association of their variables with a risk or a protective factor was studied. RESULTS: A total of 136 women were recruited, of whom 8 were lost to follow-up and 7 were excluded. Of the remaining 121 patients, 22 had a time to delivery <7 days and 31 had a time to delivery <14 days, and 30 deliveries occurred with a gestational age at delivery ≤34 weeks and 55 with a gestational age at delivery ≤37 weeks. Univariate binary logistic regression models fitted with the log transformation of interleukin-6 showed the greatest F2-scores in most studies, which outperformed those of models fitted with placental alpha microglobulin-1 (log[interleukin-6] vs placental alpha microglobulin-1 in time to delivery <7 days: 0.38 vs 0.30; time to delivery <14 days: 0.58 vs 0.29; gestational age at delivery ≤34 weeks: 0.56 vs 0.29; gestational age at delivery ≤37 weeks: 0.61 vs 0.16). Multivariate logistic regression models fitted with imbalanced data sets outperformed most univariate models (F2-score in time to delivery <7 days: 0.63; time to delivery <14 days: 0.54; gestational age at delivery ≤34 weeks: 0.62; gestational age at delivery ≤37 weeks: 0.73). The performance of prediction of multivariate models was drastically improved when data sets were balanced, and was maximum for time to delivery <7 days (F2-score: 0.88±0.2; positive predictive value: 0.86±0.02; negative predictive value: 0.89±0.03). CONCLUSION: A multivariate assessment including interleukin-6 may lead to more targeted treatment, thus reducing unnecessary hospitalization and avoiding unnecessary maternal-fetal treatment.

Uterine slow wave: directionality and changes with imminent delivery.

Objective.The slow wave (SW) of the electrohysterogram (EHG) may contain relevant information on the electrophysiological condition of the uterus throughout pregnancy and labor. Our aim was to assess differences in the SW as regards the imminence of labor and the directionality of uterine myoelectrical activity.Approach. The SW of the EHG was extracted from the signals of the Icelandic 16-electrode EHG database in the bandwidth [5, 30] mHz and its power, spectral content, complexity and synchronization between the horizontal (X) and vertical (Y) directions were characterized by the root mean square (RMS), dominant frequency (domF), sample entropy (SampEn) and maximum cross-correlation (CCmax) of the signals, respectively. Significant differences between parameters at time-to-delivery (TTD) ≤7 versus >7 days and between the horizontal versus vertical directions were assessed.Main results.The SW power significantly increased in both directions as labor approached (TTD ≤ 7d versus >7d (mean±SD):RMSx = 0.12 ± 0.10 versus 0.08 ± 0.06 mV;RMSy = 0.12 ± 0.09 versus 0.08 ± 0.05 mV), as well as the dominant frequency in the horizontal direction (domFx= 9.1 ± 1.3 versus 8.5 ± 1.2mHz) and the synchronization between both directions (CCmax= 0.44 ± 0.16 versus 0.36 ± 0.14). Furthermore, its complexity decreased in the vertical direction (SampEny= 6.13·10-2 ± 8.7·10-3versus 6.50·10-2 ± 8.3·10-3), suggesting a higher cell-to-cell electrical coupling. Whereas there were no differences between the SW features in both directions in the general population, statistically significant differences were obtained between them in individuals in many cases.Significance.Our results suggest that the SW of the EHG is related to bioelectrical events in the uterus and could provide objective information to clinicians in challenging obstetric scenarios.

Treatment of Dyspareunia with Botulinum Neurotoxin Type A: Clinical Improvement and Influence of Patients' Characteristics.

The treatment of chronic pelvic pain (CPP) with botulinum neurotoxin type A (BoNT/A) has increased lately, but more studies assessing its effect are needed. This study aimed to evaluate the evolution of patients after BoNT/A infiltration and identify potential responders to treatment. Twenty-four women with CPP associated with dyspareunia were treated with 90 units of BoNT/A injected into their pelvic floor muscle (PFM). Clinical status and PFM activity were monitored in a previous visit (PV) and 12 and 24 weeks after the infiltration (W12, W24) by validated clinical questionnaires and surface electromyography (sEMG). The influence of patients' characteristics on the reduction in pain at W12 and W24 was also assessed. After treatment, pain scores and the impact of symptoms on quality of life dropped significantly, sexual function improved and sEMG signal amplitude decreased on both sides of the PFM with no adverse events. Headaches and bilateral pelvic pain were risk factors for a smaller pain improvement at W24, while lower back pain was a protective factor. Apart from reporting a significant clinical improvement of patients with CPP associated with dyspareunia after BoNT/A infiltration, this study shows that clinical characteristics should be analyzed in detail to identify potential responders to treatment.

Effect of BoNT/A in the Surface Electromyographic Characteristics of the Pelvic Floor Muscles for the Treatment of Chronic Pelvic Pain.

Chronic pelvic pain (CPP) is a complex condition with a high economic and social burden. Although it is usually treated with botulinum neurotoxin type A (BoNT/A) injected into the pelvic floor muscles (PFM), its effect on their electrophysiological condition is unknown. In this study, 24 CPP patients were treated with BoNT/A. Surface electromyographic signals (sEMG) were recorded at Weeks 0 (infiltration), 8, 12 and 24 from the infiltrated, non-infiltrated, upper and lower PFM. The sEMG of 24 healthy women was also recorded for comparison. Four parameters were computed: root mean square (RMS), median frequency (MDF), Dimitrov's index (DI) and sample entropy (SampEn). An index of pelvic electrophysiological impairment (IPEI) was also defined with respect to the healthy condition. Before treatment, the CPP and healthy parameters of almost all PFM sides were significantly different. Post-treatment, there was a significant reduction in power (MDF), lower fatigue index (SampEn) in all sites in patients, mainly during PFM contractions, which brought their electrophysiological condition closer to that of healthy women (

Characterization of Pelvic Floor Activity in Healthy Subjects and with Chronic Pelvic Pain: Diagnostic Potential of Surface Electromyography.

Chronic pelvic pain (CPP) is a highly disabling disorder in women usually associated with hypertonic dysfunction of the pelvic floor musculature (PFM). The literature on the subject is not conclusive about the diagnostic potential of surface electromyography (sEMG), which could be due to poor signal characterization. In this study, we characterized the PFM activity of three groups of 24 subjects each: CPP patients with deep dyspareunia associated with a myofascial syndrome (CPP group), healthy women over 35 and/or parous (>35/P group, i.e., CPP counterparts) and under 35 and nulliparous (<35&NP). sEMG signals of the right and left PFM were recorded during contractions and relaxations. The signals were characterized by their root mean square (RMS), median frequency (MDF), Dimitrov index (DI), sample entropy (SampEn), and cross-correlation (CC). The PFM activity showed a higher power (>RMS), a predominance of low-frequency components (DI), greater complexity (>SampEn) and lower synchronization on the same side (35/P group. The same trend in differences was found between healthy women (<35&NP vs. >35/P) associated with aging and parity. These results show that sEMG can reveal alterations in PFM electrophysiology and provide clinicians with objective information for CPP diagnosis.