Case Report: Effect of rTMS on urinary incontinence in major vascular neurocognitive disorder

Introduction

UI was one of the most troublesome difficults, especially in ageing and people with dementia. Not only did UI bring a lot of inconvenences to the symptom-bearing family, but also present great challenges to clinicians for its intractable nature.

To relieve symptoms of UI, many methods have emerged in past decades, such as physiotherapy, psychological care, manual assistance, behavior therapy, drug therapy, urethral catheterization, and surgical treatment.^1,2 Among those invasive methods, pelvic floor muscle training (PFM) was proven to be effective and recommended as the first option,^3–5 and series of novel PFM programs were launched.⁶

rTMS was also attempted to treat UI in recent years. rTMS was proved to be a safety therapeutic way which was widely used for many kinds of diseases. rTMS effect on disease was depended on the stimulus hotspot, intensity, frequency and pattem. Since rTMS was one of newly emerging therapeutics, more and more explorations about the relationship between rTMS and UI would be accumulated.

Here we reported a case of rTMS on UI in a patient suffering probable major vascular neurocognitive disorder for peer discussion.

Case report

A 67-year-old female Chinese Han farmer suffered from UI over two weeks. She had received intravenous levofloxacin (Levofloxacin Lactate and Sodium Chloride Injection, Zhejiang Medicine Co., Ltd., 0.4 g qd) and pelvic floor electrical stimulation for a week before her admission, but little therapeutic effect was produced. She was hospitalized in Huanggang Central Hospital of Yangtze University. She had no awareness of her urination. Her caregiver noticed her urination from her soaked clothes and sheets. She was not unconscious and had no paralysis, numbness or ataxia. She did not complain of headache, dizziness, diplopia, or tinnitus and had no difficulty swallowing. She was poor in spirit, appetite and sleep, and her bowel movements required medical assistance. She had no medical records of hypertension, diabetes, heart disease, cerebrovascular disease or head trauma and no substance abuse or mental stimulation. However, over the past several years, she had experienced insidious onset and gradual progression of impaired cognitive function, manifesting in language, memory and perceptual-motor domains.

At admission, she was aware but had little interaction with her surroundings. A significant decline in most cognitive domains was found. She had difficulty making out others’ words, and her sentences were hard to understand. Her recent memory was heavily impaired. She hardly made decisions or planned instrumental activities. She scored seven on the mini-mental state examination (MMSE) test with partially preserved language. Her clock drawing task scored therewith only irregularly rounded shape and several numbers out of circle. Her clinical dementia rating (CDR) test score was two.

The routine blood tests were normal. The urine routine test showed no inflammatory variation. Serum liver function, kidney function, electrolytes and homocysteine were normal. Serum triglycerides and total cholesterol were elevated to 4.83 mmol/L and 7.0 mmol/L, respectively. Fasting plasma glucose was normal, while serum glycosylated hemoglobin was increased up to 7.2%. Serum thyroid-stimulating hormone, free triiodothyronine and free tetraiodothyronine were normal. Serum vitamin B12 decreased to 129.0 pg/ml. The serum was negative for antibodies against hepatitis C, syphilis, and AIDS. Electrocardiography showed sinus rhythm with no abnormalities in QRS intervals or QT intervals or ST-T changes. Chest computed tomography examination manifested as chronic bronchitis. Color Doppler ultrasound examination of the heart, digestive system, urinary system, and carotid vertebral artery was normal. Magnetic resonance imaging (MRI) of the brain showed patchy lesions around the lateral ventricle and scattered point lesions in the basal ganglia, corona radiata and frontal and parietal subcortical white matter, with features of hypointensity on T1-weighted images and hyperintensity on T2-weighted images. Mild frontal and temporal atrophy were detected, while the midbrain, pons and medulla were retained. Magnetic resonance angiography (MRA) detected carotid and intracranial atherosclerosis with no significant local stenosis.

According to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), we diagnosed the case as probable major vascular neurocognitive disorder. The most pressing issue was urinal incontinence.

The patient received treatment with repetitive transcranial magnetic stimulation (rTMS). A B65-type figure-eight coil connected to a MagPro X100 stimulator (Magventure Inc.) was used. Resting motor threshold (RMT) was determined by standard methods and not repeated during the treatment course. Active treatment was delivered at 90% RMT intensity. Stimulation was administered at 20 Hz with 25 stimulation trains of 30 stimuli each with a 30-second intertrain interval. The hot spot of stimulation was located at the bilateral paracentral lobule. In addition, intramuscular injection of vitamin B12 and oral medications to control blood sugar and cholesterol were carried out during the rTMS intervention.

The symptom of UI was markedly improved since the third rTMS therapeutic day. After a five-day course of rTMS intervention, the patient reported full awareness of her urination. Another two five-day courses of rTMS were administrated, her UI did not relapse but her neurocognitive decline had not improved at all. The scores of MMSE and CDR were the same as before treatment.

Discussion

In this case, an elderly female patient suffering from UI had received intravenous antibiotics and pelvic floor electrical stimulation for a week before her admission, but little therapeutic effect was produced. After her admission, high-frequency rTMS on the bilateral paracentral lobule was conducted, and her urination function recovered in one week. During the two weeks of rTMS treatment, the symptom of UI disappeared without any fluctuation. Therefore, we speculated that rTMS in cortical urologic centers is useful for the remission of UI.

According to the definitions from International Continence Society Standardization of Terminology reports,⁷ the patient was classified into the type of continuous urinary incontinence from her storage symptoms. Multiple factors may contribute to the formation of this patient’s condition. In addition to the normal structure of the bladder and urethral canal, proper function of the detrusor muscle, internal and external urethral sphincters, and nervous system plays important roles during the whole urination process. The cerebral cortex and pontine nucleus coordinate the activities of sympathetic and parasympathetic networks with the somatic nervous system through spinal cord conduction tracts.⁸

To relieve symptoms of UI, many methods have emerged in past decades, such as physiotherapy, psychological care, manual assistance, behavior therapy, drug therapy, urethral catheterization, and surgical treatment.^1,2 Among those invasive methods, pelvic floor muscle training (PFM) was proven to be effective and recommended as the first option,^3–5 and a novel PFM program was launched.⁶ Based on a series of clinical trials on intravaginal electrical stimulation,⁹ transcutaneous electrical nerve stimulation,¹⁰ neuromuscular electrical stimulation¹¹ and transcutaneous tibial nerve stimulation,¹² Ali et al.,⁴ summarized that electrical stimulation was beneficial for improving the symptoms of urge urinary incontinence among people with multiple sclerosis and those with stroke. To cure voiding dysfunction due to spinal cord lesions, sacral neuromodulation (SNM) system implantation is considered to be a safe and effective method in clinical practice.^13–16 Averbeck et al., reviewed recent literature and regarded SNM as a promising therapy for neurogenic lower urinary tract dysfunction in carefully selected patients with incomplete lesions.¹⁷

rTMS was also attempted to treat UI. Yani et al., reported that high-frequency rTMS in the supplementary motor area (SMA) of the cortex decreased pelvic floor tone, while low-frequency rTMS in the SMA increased pelvic floor tone.¹⁸ A randomized controlled study was ongoing to explore the effect of posterior tibial nerve stimulation (PTNS) and rTMS on the neurogenic bladder with multiple sclerosis.¹⁹ According to a review by Pericolini et al., spinal cord stimulation (SCS) and TMS for treating lower tract symptoms in MS patients were effective despite a small number of studies.²⁰ El-Habashy et al., saw that cortical as well as sacral magnetic stimulation showed a significant effect on lower urinary tract dysfunction in MS patients with underactive bladder rather than overactive bladder.²¹ Vacher et al., collected data from the literature and found that TMS may have a role in the management of pelvic and perineal disorders.²²

Through administrating a series of impulses at specific intensity and frequency on selected brain cortex,²³ rTMS could generate post stimulation changes that affect the resting membrane potential and action potential of the selected area. Then, rTMS may induce morpho-functional modifications by increasing synaptic connectivity and modulating synaptic plasticity.^24–27 Cirillo et al.,²⁸ reported that brain rTMS was a valuable tool for cognitive rehabilitation of mild cognitive impairment through the long-term modulation of the metalloprotease- and metalloprotease-related tissue inhibitor 1 system. In this case of UI in a patient with major vascular neurocognitive disorder, we administered high-frequency rTMS to the bilateral paracentral lobule, and the symptom of UI disappeared quickly. We speculated that the therapeutic mechanism was in line with the effect of rTMS on morpho-functional modifications of neural cells and brain networks.

After all, there were several factors that could be attributed to the recovery of the patient’s UI. Firstly, that vitamin B12 supplementation and professional nursing care might help to improve the patient’s urinal symptom. Secondly, the clinical manifestation of vascular neurocognitive disorder tends to fluctuate, so, the urinal incontinence symptom may disappear along with the temporarily relief of vascular neurocognitive disorder. Thirdly, intravenous levofloxacin and pelvic floor electrical stimulation before admission might have an effect on the mitigation of urinal symptoms. Whatever, the patient’s UI began to recover and disappeared just after rTMS treatment was added. For rTMS we focused on the bilateral paracentral lobule, which is the cortical center of urination. So we regarded that rTMS being applied to the bilateral paracentral lobule could be used for treating UI in patients with major vascular neurocognitive disorder. More clinical case collections and controlled trials are needed to verify this result.

Informed consent

Written informed consent for publication of their clinical details was obtained from the daughter of the patient.