**1. Introduction**

The spinal cord can be affected by various disorders, which may be classified into traumatic or non-traumatic. Traumatic injuries are often marked by distinct events, whereas non-traumatic injuries are caused by medical conditions, including degenerative, autoimmune, vascular, infectious, or neoplastic diseases. The leading etiology for non-traumatic disease is cervical spondylosis, followed by multiple sclerosis and tumors [1]. The most common causes of traumatic injuries are vehicular accidents and falls. According to the National Spinal Cord Injury Statistical Center (Birmingham, AL, USA), the annual incidence of traumatic spinal cord injury (SCI) is approximately 54 cases per one million people in the United States [2]. The average age is 43, and 78% of the affected patients are male. The cervical spine is the most common site of injury, comprising more than 50% of the cases [3].

The high prevalence of C-spine SCI results in multi-organ dysfunction. Cardiac risks are elevated due to a more prevalent adverse lipid profile, insulin resistance, and abnormal glucose metabolism in SCI patients. Pneumonia is frequent due to an impairment of the respiratory muscles and poor clearance of lung secretions. Constipation is common in

**Citation:** Chow, P.-M.; Kuo, H.-C. Botulinum Toxin A Injection for Autonomic Dysreflexia—Detrusor Injection or Urethral Sphincter Injection? *Toxins* **2023**, *15*, 108. https://doi.org/10.3390/ toxins15020108

Received: 14 December 2022 Revised: 19 January 2023 Accepted: 24 January 2023 Published: 26 January 2023

**Copyright:** © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

patients who have injuries above the conus medullaris, resulting in hypertonic pelvic muscles. Pressure ulcers are directly related to immobility, and are difficult to manage in SCI patients [4]. The immobility resulting from either tetraplegia or paraplegia further aggravates cardiac, respiratory, metabolic, wound, and urinary complications through deprivation of exercises, muscle power reduction, sensation impairment, and fluid and nutritional imbalance. Higher mortality from the above conditions is observed in these patients due to their atypical presentations and delayed diagnosis. Multi-organ dysfunction also shortens the life expectancy of SCI patients to approximately 90 percent that of the normal population [5].

Bladder function is altered in SCI patients regardless of the level of the lesion [6]. In higher-level injuries, uninhibited contraction of the detrusor muscle results in detrusor hyperreflexia, with or without bladder sensation, leading to urinary incontinence, poor bladder compliance, and vesicoureteral reflux. These disorders can be worsened by the un-relaxation or dyssynergic contraction of the external sphincter during the voiding phase, which further increases intravesical pressure. In lower-level injuries, acontractile detrusors result in urinary retention, and insufficient sphincters result in urinary incontinence [7]. Both storage and voiding function require assistance to maintain a low-pressure, compliant, contractile bladder, as well as a continent sphincter. The wellness of the bladder directly reflects the quality of life in terms of the reduction in infection, stone formation, ureteral reflux, and renal function impairment [8].

Autonomic dysreflexia (AD) is a distinct cardiovascular complication commonly seen in SCI above T6. The injury separates the sympathetic neurons from the supraspinal regulation, resulting in a decentralized cord. An episode of AD presents with hypertension and concomitant baroreflex-mediated bradycardia, initiated by unmodulated sympathetic reflexes [9]. The reflex is often triggered by a stimulation below the injury level, such as constipation, bladder distention, pressure sores, or even tight clothing in SCI patients. During an episode of AD, the systolic pressure can reach as high as 325 mmHg [10]. Hypertensive crisis can result in cardiac arrest, seizure, stroke, or sudden death. In patients with SCI and neurogenic bladder, episodes of AD can be discerned by their symptoms, including headache, sweating, and flushing above the injured level.

Intravesical injection of botulinum toxin A (Botox) is a standard therapy for neurogenic detrusor overactivity (NDO). The toxin works on the neuro-muscular junction and relaxes the detrusor muscle, thus improving bladder compliance and reducing urinary incontinence [11]. Another application of Botox is urethral sphincter injection for the purpose of lowering bladder outlet resistance [12]. Both detrusor and urethral sphincter injections of Botox can theoretically improve AD by reducing intravesical pressure during storage and reducing bladder outlet resistance during voiding. However, few studies have investigated the clinical effect of Botox on AD. Schurch et al. first reported the disappearance of AD in 3 of 31 SCI patients who received botulinum-A toxin injections [13]. Fougere et al. found that AD was reduced and blood pressure was stabilized after botulinum-A toxin injections in 17 patients [14]. Herein, we report our experience with Botox injection in either the detrusor or the urethral sphincter, and its effect on AD in patients with SCI.
