Salazar Betsy H, Hoffman Kristopher A, Lincoln John A, Karmonik Christof, Rajab Hamida, Helekar Santosh A, Khavari Rose
Department of Urology, Houston Methodist Hospital, 6560 Fannin St. Suite 2100, Houston, TX, 77030, USA.
Translational Imaging Center, Houston Methodist Research Institute, Houston, TX, USA.
BMC Urol. 2024 Jan 25;24(1):20. doi: 10.1186/s12894-023-01358-8.
Multiple Sclerosis (MS) is an often debilitating disease affecting the myelin sheath that encompasses neurons. It can be accompanied by a myriad of pathologies and adverse effects such as neurogenic lower urinary tract dysfunction (NLUTD). Current treatment modalities for resolving NLUTD focus mainly on alleviating symptoms while the source of the discomfort emanates from a disruption in brain to bladder neural circuitry. Here, we leverage functional magnetic resonance imaging (fMRI), repetitive transcranial magnetic stimulation (rTMS) protocols and the brains innate neural plasticity to aid in resolving overactive bladder (OAB) symptoms associated with NLUTD.
By employing an advanced neuro-navigation technique along with processed fMRI and diffusion tensor imaging data to help locate specific targets in each participant brain, we are able to deliver tailored neuromodulation protocols and affect either an excitatory (20 min @ 10 Hz, applied to the lateral and medial pre-frontal cortex) or inhibitory (20 min @ 1 Hz, applied to the pelvic supplemental motor area) signal on neural circuitry fundamental to the micturition cycle in humans to restore or reroute autonomic and sensorimotor activity between the brain and bladder. Through a regimen of questionnaires, bladder diaries, stimulation sessions and analysis, we aim to gauge rTMS effectiveness in women with clinically stable MS.
Some limitations do exist with this study. In targeting the MS population, the stochastic nature of MS in general highlights difficulties in recruiting enough participants with similar symptomology to make meaningful comparisons. As well, for this neuromodulatory approach to achieve some rate of success, there must be enough intact white matter in specific brain regions to receive effective stimulation. While we understand that our results will represent only a subset of the MS community, we are confident that we will accomplish our goal of increasing the quality of life for those burdened with MS and NLUTD.
This trial is registered at ClinicalTrials.gov (NCT06072703), posted on Oct 10, 2023.
多发性硬化症（MS）是一种常使人衰弱的疾病，会影响包裹神经元的髓鞘。它可能伴有多种病理状况和不良反应，如神经源性下尿路功能障碍（NLUTD）。目前解决NLUTD的治疗方式主要集中在缓解症状，而不适的根源是大脑与膀胱神经回路的中断。在此，我们利用功能磁共振成像（fMRI）、重复经颅磁刺激（rTMS）方案以及大脑固有的神经可塑性，来帮助解决与NLUTD相关的膀胱过度活动症（OAB）症状。
通过采用先进的神经导航技术以及处理后的fMRI和弥散张量成像数据，以帮助在每个参与者的大脑中定位特定靶点，我们能够提供量身定制的神经调节方案，并对人类排尿周期的基本神经回路上施加兴奋性（10赫兹，20分钟，施加于外侧和内侧前额叶皮层）或抑制性（1赫兹，20分钟，施加于骨盆辅助运动区）信号，以恢复或重新引导大脑与膀胱之间的自主神经和感觉运动活动。通过一系列问卷调查、膀胱日记、刺激疗程和分析，我们旨在评估rTMS对临床病情稳定的MS女性患者的有效性。
本研究确实存在一些局限性。针对MS人群，MS的随机性总体上凸显了招募足够多具有相似症状的参与者以进行有意义比较的困难。此外，对于这种神经调节方法要取得一定的成功率，特定脑区必须有足够完整的白质来接受有效刺激。虽然我们明白我们的结果仅代表MS群体的一个子集，但我们相信我们将实现提高那些患有MS和NLUTD患者生活质量的目标。
本试验已在ClinicalTrials.gov（NCT06072703）注册，于2023年10月10日发布。
