Neuromodulación sacral como alternativa terapéutica en la disinergia vesico esfinteriana.

Presentamos una experiencia y comentarios sobre neuromodulación y vejiga neurogénica. Evaluamos 32 pacientes con estimulación percutánea previa (PNE), positiva en 20 casos y negativa en 12. Los diagnósticos en las PNE negativas fueron: 7 vejigas hiperrrefléxicas, 3 vejigas neurógenas atónicas no obstructivas, 1 síndrome cortical con vejiga neurógena no inhibida y un síndrome doloroso vesical. Los mejores resultados son en vejigas hiperrrefléxicas con mejoría del 60-70%, con un seguimiento de hasta 4 años.

Esclerosis múltiple. : nuestra experiencia

Objetivos: analizar la experiencia obtenida y evaluar los resultados urodinámicos del estudio de 18 pacientes con esclerosis múltiple. Material y Métodos: se estudiaron 18 casos, valorándose la historia clínica, ecografía vesical y renal, analizándolos urodinámicamente con uroflujometría, residuo post miccional (RPM), cistotonometría y electromiografía esfinteriana. Urocultivo y antibiograma de orina. Resultados: del análisis de todas las variables se desprende que la vejiga hiperactiva se presentó en 10 casos con un predominio del síndrome frecuencia-urgencia, vejiga hipotónica-hiporrefléxica en 5 pacientes, disinergia detrusor-esfínter en 4 casos y 9 pacientes con infección urinaria que desencadenaban crisis de espasticidad. Todos fueron tratados con anticolinérgicos de acción vesical inmuno-modulación (brotes-recaídas) e inmuno-supresión en la enfermedad progresiva, de rehabilitación y terapia de apoyo psicológico. Conclusión: la vejiga hiperactiva es el tipo de consecuencia urinaria de la esclerosis en placa con los síntomas de frecuencia-urgencia y que, con tratamiento multimodal mejoran en un alto porcentaje.

Bexiga hiperactiva e utilização de toxina botulínica na hiperactividade do detrusor : resultados obtidos pelo Serviço de Urologia do HSM-CHLN

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Quantitative Analysis of Kilohertz-Frequency Neurostimulation

Mainstream electrical stimulation therapies, e.g., spinal cord stimulation (SCS) and deep brain stimulation, use pulse trains that are delivered at rates no higher than 200 Hz. In recent years, stimulation of nerve fibers using kilohertz-frequency (KHF) signals has received increased attention due to the potential to penetrate deeper in the tissue and to the ability to block conduction of action potentials. As well, there are a growing number of clinical applications that use KHF waveforms, including transcutaneous electrical stimulation (TES) for overactive bladder and SCS for chronic pain. However, there is a lack of fundamental understanding of the mechanisms of action of KHF stimulation. The goal of this research was to analyze quantitatively KHF neurostimulation.

We implemented a multilayer volume conductor model of TES including dispersion and capacitive effects, and we validated the model with in vitro measurements in a phantom constructed from dispersive materials. We quantified the effects of frequency on the distribution of potentials and fiber excitation. We also quantified the effects of a novel transdermal amplitude modulated signal (TAMS) consisting of a non-zero offset sinusoidal carrier modulated by a square-pulse train. The model revealed that high-frequency signals generated larger potentials at depth than did low frequencies, but this did not translate into lower stimulation thresholds. Both TAMS and conventional rectangular pulses activated more superficial fibers in addition to the deeper, target fibers, and at no frequency did we observe an inversion of the strength-distance relationship. In addition, we performed in vivo experiments and applied direct stimulation to the sciatic nerve of cats and rats. We measured electromyogram and compound action potential activity evoked by pulses, TAMS and modified versions of TAMS in which we varied the amplitude of the carrier. Nerve fiber activation using TAMS showed no difference with respect to activation with conventional pulse for carrier frequencies of 20 kHz and higher, regardless the size of the carrier. Therefore, TAMS with carrier frequencies >20 kHz does not offer any advantage over conventional pulses, even with larger amplitudes of the carrier, and this has implications for design of waveforms for efficient and effective TES.

We developed a double cable model of a dorsal column (DC) fiber to quantify the responses of DC fibers to a novel KHF-SCS signal. We validated the model using in vivo recordings of the strength-duration relationship and the recovery cycle of single DC fibers. We coupled the fiber model to a model of SCS in human and applied the KHF-SCS signal to quantify thresholds for activation and conduction block for different fiber diameters at different locations in the DCs. Activation and block thresholds increased sharply as the fibers were placed deeper in the DCs, and decreased for larger diameter fibers. Activation thresholds were > 5 mA in all cases and up to five times higher than for conventional (~ 50 Hz) SCS. For fibers exhibiting persistent activation, the degree of synchronization of the firing activity to the KHF-SCS signal, as quantified using the vector strength, was low for a broad amplitude range, and the dissimilarity between the activities in pairs of fibers, as quantified using the spike time distance, was high and decreased for more closely positioned fibers. Conduction block thresholds were higher than 30 mA for all fiber diameters at any depth and well above the amplitudes used clinically (0.5 – 5 mA). KHF-SCS appears to activate few, large, superficial fibers, and the activated fibers fire asynchronously to the stimulation signal and to other activated fibers.

The outcomes of this work contribute to the understanding of KHF neurostimulation by establishing the importance of the tissue filtering properties on the distribution of potentials, assessing quantitatively the impact of KHF stimulation on nerve fiber excitation, and developing and validating a detailed model of a DC fiber to characterize the effects of KHF stimulation on DC axons. The results have implications for design of waveforms for efficient and effective nerve fiber stimulation in the peripheral and central nervous system.

Bladder interstitial cells:an updated review of current knowledge

The field of bladder research has been energized by the study of novel interstitial cells (IC) over the last decade. Several subgroups of IC are located within the bladder wall and make structural interactions with nerves and smooth muscle, indicating integration with intercellular communication and key physiological functions. Significant progress has been made in the study of bladder ICs' cellular markers, ion channels and receptor expression, electrical and calcium signalling, yet their specific functions in normal bladder filling and emptying remain elusive. There is increasing evidence that the distribution of IC is altered in bladder pathophysiologies suggesting that changes in IC may be linked with the development of bladder dysfunction. This article summarizes the current state of the art of our knowledge of IC in normal bladder and reviews the literature on IC in dysfunctional bladder.

Is the ultrasound-estimated bladder weight a reliable method for evaluating bladder outlet obstruction?

OBJECTIVETo evaluate the correlation between ultrasound-estimated bladder weight (UEBW) in patients with different degrees of bladder outlet obstruction (BOO).METHODSWe evaluated 50 consecutive non-neurogenic male patients with lower urinary tract symptoms (LUTS) referred to urodynamic study (UDS). All patients self-answered the International Prostate Score Symptoms (IPSS) questionnaire. After the UDS, the bladder was filled with 150 mL to determine UEBW.Patients with a bladder capacity under 150 mL, a previous history of prostate surgery or pelvic irradiation, an IPSS score <8, a bladder stone or urinary tract infection were excluded.After a pressure-flow study, the Schafer linear passive urethral resistance relation nomogram was plotted to determine the grade of obstruction: Grades I-II/VI were defined as mild obstruction, Grades III-IV/VI as moderate obstruction, and Grades V-VI/VI as severe obstruction.RESULTSThe UEBW was 51.7 +/- 26.9, 54.1 +/- 30.0 and 54.8 +/- 28.2 in patients with mild, moderate and severe BOO, respectively (P = 0.130). The UEBW allowed us to define four groups: (i) UEBW < 35 g; (ii) 35 g <= UEBW < 50 g; (iii) 50 g <= UEBW < 70 g; and (4) UEBW >= 70 g.We did not find any differences in age, prostate weight, IPSS, PVR, cystometric bladder capacity, presence of detrusor overactive and degree of obstruction in the aforementioned groups.CONCLUSIONDespite the fact that some studies have emphasized the value of UEBW as an efficient non-invasive method for evaluating lower urinary tract obstruction, our study suggests that UEBW does not present any individual correlation with LUTS or objective measurements of BOO.

A pilot study of Connexin 43 (Cx43) in human bladder tissue in patients with idiopathic detrusor overactivity

OBJECTIVE: Aim of the study was to compare Connexin 43 (Cx43) in human bladder tissue of urodynamically proven idiopathic detrusor overactivity to those of urodynamically stable bladders. STUDY DESIGN: We compared bladder biopsies of patients with detrusor overactivity and those with stable bladder analysing Cx43 message by RNA extraction and PCR amplification. All patients had multichannel urodynamics prior to the biopsies. RESULTS: We investigated the bladder biopsies of 15 female patients with and 15 patients without detrusor overactivity. Cx43 could be detected in nine patients of the detrusor overactivity group and in eight patients of the control group which was not statistically significant. 42 cycles of PCR were necessary to demonstrate Cx43 presence in the positive specimen. The presence of Cx43 was not consistent in the samples from the bladder dome and the side walls meaning there were Cx43 positive results in the dome and negative ones in the side walls of the same patient and vice versa. CONCLUSION: In conclusion, Cx43 is present in human bladder tissue both of overactive bladders and those of controls. However, it is expressed in very small amounts and is not always detectable. The role of Cx43 for the origin of detrusor overactivity remains unclear.

Reduced Thrombospondin-1 at presentation predicts disease progression in superficial bladder cancer

Objectives: Superficial bladder cancer (SBC) presents a difficult clinical dilemma at diagnosis as only a small subgroup of patients will subsequently develop invasive disease. Study of cancer biology has found that angiogenesis is central to growth and spread. This study examines the relationship between the angiogenic inhibitory factor Thrombospondin-1 (TSP-1) at initial presentation and subsequent progression of SBC. Methods: Using immunohistochemistry, 220 cases of SBC were examined for pattern and extent of expression of TSP-1 at initial presentation. Results: TSP-1 was detected in perivascular tissue, at the epithelial-stromal junction, in the stroma and in tumour cells and reduced perivascular TSP-1 staining at presentation was an independent predictive factor for the subsequent development of muscle invasive or metastatic disease. Conclusion: This adds further weight to the theory that TSP-1 plays a major part in the biology of bladder cancer possibly through the control of angiogenesis. © 2002 Elsevier Science B.V. All rights reserved.

Carbonic anhydrase IX expression and outcome after radiotherapy for muscle-invasive bladder cancer

Aims: Carbonic anhydrase IX (CA IX) expression has been described as an endogenous marker of hypoxia in solid neoplasms. Furthermore, CA IX expression has been associated with an aggressive phenotype and resistance to radiotherapy. We assessed the prognostic significance of CA IX expression in patients with muscle-invasive bladder cancer treated with radiotherapy. Materials and methods: A standard immunohistochemistry technique was used to show CA IX expression in 110 muscle-invasive bladder tumours treated with radiotherapy. Clinicopathological data were obtained from medical case notes. Results: CA IX immunostaining was detected in 89 (∼81%) patients. Staining was predominantly membranous, with areas of concurrent cytoplasmic and nuclear staining and was abundant in luminal and perinecrotic areas. No significant correlation was shown between the overall CA IX status and the initial response to radiotherapy, 5-year bladder cancer-specific survival or the time to local recurrence. Conclusions: The distribution of CA IX expression in paraffin-embedded tissue sections seen in this series is consistent with previous studies in bladder cancer, but does not provide significant prognostic information with respect to the response to radiotherapy at 3 months and disease-specific survival after radical radiotherapy. © 2007 The Royal College of Radiologists.