Multiple Beneficial Effects of High-dose BoNT-A Injection to Improve Wound Healing and Spasticity in a Patient With Hypoxic Encephalopathy Due to High-voltage Electrical Injury

Introduction. High-voltage electrical injuries remain a difficult challenge for physicians. The survivors often have complicated wounds over the trunk or extremities, and some of them may develop hypoxic encephalopathy. The emergence of spasticity following hypoxic encephalopathy may further interfere with the healing of wounds. Case Report. The authors report the case of a 17-year-old male with strong spasticity of finger flexors graded 4 by the Modified Ashworth Scale (0–5) after electric shock. He also had a nonhealing wound on the flexor side of the left index finger after 6 weeks of standard wound care. The wound measured 0.3 cm × 0.3 cm × 0.2 cm in size. The authors hypothesized that wound healing was negatively affected by spasticity and expected the wound might heal gradually after reducing the strong spasticity of the index finger. The authors employed electrical stimulator for guidance and injected high-dose (50 units/muscle) botulinum toxin type A into the flexor digitorum superficialis and the flexor digitorum profundus of his left index finger. At 7 days following administration, focal spasticity of these muscles in the left index finger decreased from 4 to 1 on the Modified Ashworth Scale. At 21 days post administration, the wound healed completely. Conclusions. For patients with hypoxic encephalopathy due to high-voltage electrical injury, botulinum toxin type A injection may be an option of therapeutic approach for both reduction of spasticity and facilitation of wound healing.

Electrical injuries are common in certain workplaces, with about one-third of all electrical trauma and most high-voltage injuries being job-related.¹ Clinical manifestations of electrical injuries depend on the degree of injury, ranging from transient unpleasant sensations to widespread tissue damage or even death. The incidence of brain injury after high-voltage electricity damage is high.² The injury in the brain may be related to the effects of electrical current on the brain tissue or hypoxia after cardiopulmonary arrest.³

Patients enduring from central nervous system (CNS) damage after high-voltage electrical injuries are likely to have a spastic pattern of finger flexion with wounds over the flexor crease of the fingers,^4,5 and they may encounter barriers that impede wound healing. First, excessive moisture and poor hygiene of flexed fingers may cause maceration and deterioration to wounds. Second, high tension from spasticity also has detrimental effects on wound recovery. It causes persistent muscle contraction and diminished blood flow, which may lead to chronic inflammation of wounds that affect the healing process.⁶

Several strategies, including drugs, stretches, and splints, have been proposed for the management of excessive muscle tone due to spasticity.⁷ Medications usually cause drowsiness and weakness for the patient. Effects of stretch exercise are short acting and unsatisfactory.⁸ Splinting is a common method to keep the spastic limb in some positions for spasticity reduction. However, spasticity is the involuntary activation of muscle tone and it is dynamic. Static splinting may not be suitable, especially in the case of strong spasticity.⁹

Botulinum toxin type A (BoNT-A) is one of the neurotoxins produced by Clostridium botulinum. Botulinum toxin inhibits the release of acetylcholine from nerve terminals, which subsequently results in dose-dependent paralysis of muscles. The effect of botulinum toxin lasts for 2 to 6 months, and it is reversible, which means spasticity may gradually recur without repeat injection.^10,11 Botulinum toxin type A has been shown to successfully reduce spasticity and promote passive movement of joints.^12-15 Onabotulinum toxin A (Botox; Allergan Inc) also has been approved by the United States Food and Drug Administration to decrease muscle tone of finger flexors in patients with brain injury. The fact that BoNT-A injection diminishes contraction of muscles near the wounds may be utilized to overcome the deleterious hurdles of wound healing.

This case report conforms to all CARE guidelines (2013 CARE Checklist) and reports the required information accordingly. The authors received permission from the family and treating hospital for the off-label use of a relatively high dose of onabotulinum toxin A in a patient. The family of this patient provided written informed consent for this report and the associated images.

The purpose of this case report is to share the authors’ experience and discuss the potential benefits of high-dose BoNT-A injection to improve wound healing and spasticity in a patient with hypoxic encephalopathy due to high-voltage electrical injury.

A 17-year-old male adolescent without remarkable disease presented to the hospital after a high-voltage electrical injury while working. The patient experienced cardiac arrest upon arrival and was revived after cardiopulmonary resuscitation. Strong spasticity (Grade 4, Modified Ashworth Scale [0–5]) appeared in the left hand (Figure 1), which responded poorly to oral antispasticity medications and rehabilitation. The wound (Figure 2) caused by direct contact with electricity on the flexor site of the left index finger, which measured 0.3 cm × 0.3 cm × 0.2 cm in size, failed to close after 6 weeks of standard wound care procedures of wet dressing with normal saline and gauze coverage, as suggested by the plastic surgeon.

In addition to standard wound care, the authors attempted chemical denervation process by injecting BoNT-A into the muscle belly of the flexor digitorum superficialis (FDS) and flexor digitorum profundus (FDP) in order to weaken the muscles with strong spasticity that may interfere with wound healing. 

The authors prepared 100 units (U) of BoNT-A diluted with 1 mL of normal saline for administration. The electrical stimulator was used as guidance for localization. Then, BoNT-A was injected through a concentric, injectable, Teflon-coated, 35-mm, 27-gauge electromyography needle (Oxford Instruments). The dose for the left index finger was 50 U for the FDS and 50 U for the FDP. No complication was noted following injection.

The authors applied wet gauze dressings with normal saline in daily wound care as per the recommendation of the plastic surgeon. No splint was used because the focal spasticity ameliorated profoundly after injection. On day 7 following BoNT-A injection, focal spasticity of the FDS and FDP in the left index finger decreased from 4 to 1 (Modified Ashworth Scale) (Figure 3). The wound healed completely at 21 days following injection (Figure 4). 

Spasticity is defined as a motor disorder characterized by velocity-dependent increase in muscle tone after an upper motor neuron lesion.¹⁶ It is a common complication after brain or spinal cord injuries related to electrical damage.^4,5 The “kissing burn” is a special type of wound in patients with electrical injury, and it usually occurs at the flexor creases.¹⁷

Wound repair time can be diverse as a result of the differences in depth, extension in the subcutaneous tissue, or other conditions. The wound healing process includes the inflammatory, proliferative, and remodeling phases.¹⁸ In general, the time course of healing usually varies from 5 to 30 days.¹⁹ A chronic wound is defined as the failure to progress through the normal stages of healing in an orderly and timely manner.²⁰ In this case, the patient had severe spasticity and a chronic wound. The improvement of the wound stalled at 6 weeks after injury, which indicated poor healing status. Therefore, the authors aimed to totally immobilize the spastic muscles underlying the wound in order to facilitate its closure. 

As for the evidence and possible mechanisms of BoNT-A for improving wound care, there are animal experiments^6,21 and human trials.^2-26 available. In a randomized study conducted by Lee at al,⁶ 10 U of BoNT-A was injected into the deep musculature surrounding the wounds over the dorsum of Wistar rats. The histological results showed less infiltration of inflammatory cells and less fibrosis when compared with the placebo group.⁶ They proposed the BoNT-A injection may decrease tension of the wound as well as lessen microtrauma around the wound, which in turn reduces the inflammation response in the early stages of wound healing.⁶ In another animal study, Kim et al²¹ created a flap measuring 3 cm x 10 cm at the dorsum of 10 Sprague Dawley rats. The rats were divided into 2 groups of either intradermal injection of 20 U of BoNT-A or normal saline. Injection with BoNT-A increased the survival rate of the dorsal skin flap.²¹ They presumed the BoNT-A improved perfusion by attenuation of the sympathetic vasoconstriction in skin flaps.²¹

To the authors' knowledge, only a few clinical trials exist for botulinum toxin in wound management. In a randomized, placebo-controlled trial, Gassner et al²² found BoNT-A for chemo-immobilization of wounds over the forehead was superior to normal saline with better wound healing and less noticeable scars. Another excellent example of BoNT-A for wound healing is its application in chronic anal fissures.^23,25,26 Anal fissures are not easy to treat due to the hypertonicity of the sphincter muscles in the anus. Pain and local muscle spasms decrease the blood flow supplied to the wound, and subsequent ischemia may cause further inflammation. Sustained inflammatory status of the wound not only hinders wound closure but also exacerbates local muscle spasms and pain.²⁴ A vicious cycle may form and turn the anal fissure into a chronic wound, which would make it very difficult to repair completely; BoNT-A could break this cycle and heal the wound successfully. ^23,25,26

Regarding the dose for FDS and FDP, Brin²⁷ suggested a total of 25 U to 75 U of BoNT-A for FDS and 25 U to 100 U for FDP divided into 4 fascicles to treat spasticity for adults with CNS lesions. A review article²⁸ reported the mean total dose of BoNT-A for all 4 fascicles of FDS and FDP for management of adult spasticity to be 50.3 U and 42.0 U, respectively. Recent practice guidelines also indicated that the most frequently recommended total dose of BoNT-A for all 4 fascicles of either FDS or FDP was 50 U in adults.²⁹ In this report, the authors administered 100 U of BoNT-A in total, with 50 U into FDS and 50 U into FDP of the left index finger in a patient with strong spasticity and a nonhealing wound resulting from hypoxic encephalopathy after electrical injury. The dose of 50 U of BoNT-A for individual fascicle of FDS and FDP of the index finger in this case is at least 2 times higher than the recommended mean dose for a single fascicle. The higher dosage was used because the authors intended to achieve temporary immobilization of muscles below the wound as much as possible to enhance wound healing, rather than the usual dose for only spasticity reduction.

Due to this report having a single-case study design, the conclusions that can be drawn are limited.

The authors used a high dose of BoNT-A for its potential actions to abate muscle tone, minimize the inflammatory response, decrease vasoconstriction to increase perfusion, and chemoimmobilize the wound.^{6,12-15,21-26} All of these effects may alleviate the factors that can limit wound closure. The patient had attenuated spasticity over the left index finger on day 7, and the wound fully healed at day 21 following BoNT-A injection. Adverse events with high-dose BoNT-A injection, such as ecchymosis, pain, unintended weakness, or distant spread of botulinum toxin beyond the site of injection, did not occur in this patient. However, the dose of 50 U of BoNT-A for each fascicle of FDS and FDP of the index finger was still not high enough to achieve complete paralysis of the index finger in the present case. From the authors’ experience with this case, it is suggested that if the wound is chronic and focal spasticity is severe, the dose of BoNT-A may be titrated even higher for earlier and faster wound healing. 

Authors: Yu-Ching Lin, MD, MSc¹; I-Ling Lin, MSc²;Te-Feng Arthur Chou, MD³; Lin-Chieh Hsu, MD¹; Po-Ying Chiang, MD¹; and Wei-Pin Lin, MD¹

Affiliations: ¹Department of Physical Medicine and Rehabilitation, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; ²Department of Medical Laboratory Sciences and Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan; and ³Department of Orthopedics and Traumatology, Taipei Veterans General Hospital, Taipei, Taiwan

Correspondence: Wei-Pin Lin, MD, Attending Physician, Department of Physical Medicine and Rehabilitation, National Cheng Kung University Hospital, No.138, Sheng-Li Road, Tainan, Taiwan 704; tobyvoids@hotmail.com 

Disclosure: The authors disclose no financial or other conflicts of interest.