Predictors for outcomes of noninvasive, individualized transcranial magnetic neuromodulation in multiple sclerosis women with neurogenic voiding dysfunction

Yongchang Jang, Khue Tran, Zhaoyue Shi, Karmonik Christof, Darshil Choksi, Betsy H Salazar, John A Lincoln, Rose Khavari, Yongchang Jang, Khue Tran, Zhaoyue Shi, Karmonik Christof, Darshil Choksi, Betsy H Salazar, John A Lincoln, Rose Khavari

Abstract

Purpose: Multiple sclerosis (MS) is a multifocal demyelinating disease that affects the central nervous system (CNS) and commonly leads to neurogenic lower urinary tract dysfunction (NLUTD). Proper storage and release of urine relies on synchronized activity of the LUT, which is meticulously regulated by supraspinal circuits, making it vulnerable to diseases such as MS. NLUTD, characterized by voiding dysfunction (VD), storage issues, or a combination of both is a common occurrence in MS. Unfortunately, there are limited treatment options for NLUTD, making the search for alternative treatments such as transcranial rotating permanent magnet stimulation (TRPMS) of utmost importance. To assess effectiveness of treatment we also need to understand underlying factors that may affect outcomes, which we addressed here.

Methods: Ten MS subjects with VD and median age of 54.5 years received daily TRPMS sessions for two weeks. Five pre-determined regions of interest (ROIs) known to be involved in the micturition cycle were modulated (stimulated or inhibited) using TRPMS. Clinical data (non-instrumented uroflow and urodynamics parameters, PVR, bladder symptom questionnaires) and neuro-imaging data were collected at baseline and following TRPMS via 7-Tesla Siemens MAGNETOM Terra magnetic resonance imaging (MRI) scanner. Each participant underwent functional MRI (fMRI) concurrently with a repeated urodynamic study (UDS). Baseline data of each arm was evaluated to determine any indicators of successful response to treatment.

Keywords: Magnetic resonance imaging; Multiple sclerosis; Neuromodulation; Voiding dysfunction.

Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1.
Fig. 1.
CONSORT flow diagram.
Fig. 2.
Fig. 2.
Results of statistical analysis between responders (R) and non-responders (NR) group. Responders showed significantly lower values in first sensation of filling (FSF), consequences domain in NBSS, and number of deliveries as compared to non-responders. Numerical values from the statistical analysis are listed in Table 4. UDS: urodynamic study, MCC: maximum cystometric capacity, PVR: post-void residual, AUASS: American Urological Association Symptom Score, NBSS: Neurogenic Bladder Symptom Score, EDSS: Expanded Disability Status Scale.
Fig. 3.
Fig. 3.
Blood-oxygen-level-dependent (BOLD) signal group analysis at baseline between the responder and non-responder group (Student’s t-test values listed on the right). Red indicates significantly higher cortical activation in the responder group at voiding initiation with a positive t-value; blue indicates significantly lower activation with a negative t-value. Some examples of cortical regions with significantly higher activation in the responder group are: (a) Left anterior cingulate cortex, (b) Right inferior frontal gyrus, (c) Right middle frontal gyrus.

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