Effects of Electrical Stimulation on Facial Paralysis Recovery after Facial Nerve Injury: A Review on Preclinical and Clinical Studies
Abstract
:1. Introduction
2. Methods
3. Results
3.1. Animal Studies of Electrical Stimulation (Table 1)
3.1.1. Animal Studies Reporting Effective Electrical Stimulation Results
3.1.2. Animal Studies Reporting Ineffective Results of Electrical Stimulation
3.2. Human Studies of Electrical Stimulation (Table 2)
3.2.1. Human Studies Showing Effective Electrical Stimulation Results
3.2.2. Human Studies Showing Ineffective Electrical Stimulation Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Author | Species and/or Sample | Injury Type | Stimulation Methods : Type/Duration/Location | Experimental Design | Results/Conclusion/Suggestions |
---|---|---|---|---|---|
Effective results by electrical stimulation (ES) | |||||
Cho et al., 2022 [24] | Sprague-Dawley rats, male | Transection: main trunk of the left facial nerve was cut 10 mm and the nerve was immediately repaired | Type: charge-balanced transcutaneous electrical nerve stimulation (Cb-TENS) with a biphasic electric pulse, Duration: daily for seven days and then twice a week for 3 weeks (total 4 weeks) Location: skin patch electrode of the preauricular area | - Group 1: The control group with no TENS (n = 22). - Group 2: Injury with Cb-TENS at 20 Hz (n = 22). - Group 3: Injury with Cb-TENS at 40 Hz (n = 22). Parameters: Whisker movement Histopathological evaluation with Transmission electron microscopy (TEM) Post-injury duration: 28 days | Rats in the Cb-TENS groups showed faster and better recovery of whisker movement than those in the control group. The 40 Hz group showed significantly better movement at the first week after injury. Regeneration of the myelin sheath was remarkably rapid and thicker in the 20 Hz and 40 Hz groups than in the control group. Cb-TENS promoted and accelerated facial nerve recovery, as it significantly reduced the recovery time for whisker movement. |
Brown MS et al., 2020 [25] | Wistar rats | Transection and neurorrhaphy at main trunk of the right facial nerve | Type: fine wire electrodes Duration: 100 μs charge-balanced square waves; peak-to-peak amplitude 3 V. 20 Hz train for 30 min Location: hooked around the nerve 2 mm proximal to the intended axotomy site | - Group 1: control (n = 3). - Group 2: neurorrhaphy only (n = 4). - Group 3: neurorrhaphy + ES (n = 8). - Group 4: neurorrhaphy + ES + polyethylene glycol (PEG) (n = 8). Parameters: Eye blink reflex Whisking movement Tissue analysis Retrograde tracing | Incorporating short-duration intraoperative electrical stimulation into neurorrhaphy in this animal model demonstrates potential positive neurological effects in the surgical treatment of facial nerve injury. |
Deng et al., 2018 [26] | Sprague-Dawley rats, male | Transection: 1-cm defect surgically introduced on the right facial nerve. | Type: transcutaneous electrodes Duration: an electrical pulse of 3 V, 20 Hz and 0.3 mA for 1 h each day (total 28 days) Location: the orbicularis oris muscle of the right paralyzed face | - Group 1: main trunk of the right facial nerve transection only (n = 20) - Group 2: surgery + ES group (n = 20). - Group 3: normal control group (n = 20). Parameters: Facial muscle movement, compound muscle action potentials (CMAPs), Histological structure The expression levels of S100B and NF200. Post-injury duration: 28 days | The ES group showed a higher amplitude and shorter latency of compound muscle action potential from day 14 to 28 after surgery, as well as increased number of axons and expression of S100B and NF200 proteins. ES promotes outgrowth and myelination of axons and a partial functional recovery of facial muscles in rats with injured facial nerves. |
Mendez et al., 2018 [27] | Wistar rats | Crush and transection After transection injury, the cut nerve ends were immediately repaired by direct end-to-end anastomosis. | Type: implantable stimulation device (two silver Teflon coated wires for BES) Duration: a 1.5 mA current in pulses of 100 microseconds in a continuous 20 Hz train for a period of 1 h only. Location: first wire was looped around the proximal stump of the facial nerve. The second wire was imbedded into muscle tissue adjacent to the facial nerve. | - Group 1 (n = 6): crush injury at the main trunk of the nerve - Group 2 (n = 6): crush injury at the main trunk of the nerve + BES (1 h) - Group 3 (n = 6): transection injury at the main trunk of the nerve - Group 4 (n = 6): transection injury at the main trunk of the nerve + BES (1 h) Parameters: Facial nerve functional outcome (2, 4, and 6 weeks): whisking movement Buccal and marginal mandibular branches of the facial nerve were each injected with different neurotracers at 3 months post-injury. Post-injury duration: 6 weeks | BES (brief electrical stimulation) demonstrated improved whisking movement and pathway-specific regeneration with BES following facial nerve injury. Performing BES after facial nerve injury is associated with accelerated facial nerve function and improved facial nerve specific pathway regeneration in a rat model. |
Mendez et al., 2016 [28] | Wistar rats | Transection: right facial nerve transection and repair at the main trunk of the nerve. | Type: implantable stimulation device (two silver Teflon coated wires for BES) Duration: a 1.5 mA current in pulses of 100 microseconds in a continuous 20 Hz train for a period of 1 h only. Location: first wire was looped around the proximal stump of the facial nerve. The second wire was imbedded into muscle tissue adjacent to the facial nerve. | - Group 1 (n = 9): transection injury - Group 2 (n = 9): transection injury + BES Parameters: Facial nerve functional outcome (2, 4, and 6 weeks): whisking movement Post-injury duration: 6 weeks | In rats subjected to facial nerve transection and neurorrhaphy at the main trunk of the facial nerve, those that received BES after transection showed significantly accelerated whisker movement compared with those that did not. |
Foecking et al., 2012 [29] | Sprague -Dawley rats, male | Crush | Type: implantable stimulation device Duration: 1 ms-wide square wave direct current stimulus pulses at 20 Hz (1.5 mA, 1 s), followed by a 1s rest period. Daily 30 min sessions of ES for 1, 2, 4, or 7 d. Location: negative electrode terminal was then sutured approximately 2 mm proximal to the crush injury site and the positive electrode terminal to connective tissue about 3 to 5 mm away from the negative terminal on the opposite side of the nerve | The animals were divided into six groups (n = 6 in each group) - Group 1: no ES - Group 2: one 30 min session of ES immediately following the injury (1 session); - Group 3: Group 2 + 1 d later (total 2 sessions) - Group 4: Group 2 + 1 d to 3 d later (total 4 sessions) - Group 5: Group 2 + 1 d to 6 d later (total 7 sessions) - Group 6: stimulated daily until complete recovery. Parameters: The eye blink reflex Vibrissae movement Post-injury duration: measured until complete recovery. | One session of ES was as effective as daily stimulation at enhancing the recovery of most functional parameters. |
Kim et al., 2011 [30] | New Zealand white rabbits, male | Crush | Type: implantable stimulation device (two Teflon coated wires) Duration: Subthreshold continuous direct current ES with 20-Hz square-wave pulses for 4 weeks. Location: the proximal stump on the facial nerve | - Group 1: Crush injury + no ES - Group 2: Crush injury + 30 min session of ES (1 session only) Parameters: Electrophysiological test Histological study Functional recovery of vibrissae movement Post-injury duration: 30 days | Vibrissae movement returned significantly earlier on the ES side. Electrophysiologically, the stimulated side had a significantly shorter latency, longer duration, and faster conduction velocity. Light and transmission electron microscopy revealed that the electrical stimulation also markedly decreased Wallerian degeneration. Subthreshold, continuous, low-frequency ES immediately after a crush injury of the facial nerve results in earlier recovery of facial function and shorter overall recovery time. |
Hadlock et al., 2010 [18] | Wistar rats | Transection: immediate microsurgical repair. | Type: a hooked pair of platinum stimulating electrodes Duration: suprathreshold stimulation of the facial nerve was delivered for 60 min using a 3-V, 20-Hz square-wave Location: main trunk of the facial nerve In the MEC and BES+MEC groups, animals received 5 min of daily massage to the left whisker pad | Sixty rats were randomized to three groups (n = 20 in each group): - Group 1: BES - Group 2: mechanical stimulation of the whisker pad (MEC) - Group 3: both in combination (BES+MEC) Parameters: Whisking behavior Post-injury duration: 13 weeks | Rats that received either BES or MEC of the whisker pad showed accelerated recovery of whisking behavior. A combination of both interventions did not show accelerated recovery. |
Sharma et al., 2010 [31] | Sprague -Dawley rats, male | Crush | Type: implantable stimulation device (two Teflon coated wires) Duration: crush injury site at a frequency of 20 Hz for 30 min. Location: proximal to the crush injury | The rats were randomized to eight groups (n = 4–8 in each group): - Group 1: control - Group 2: prednisone (P) only - Group 3: ES only - Group 4: ES + P - Group 5: systemic testosterone propionate (TP) only - Group 6: TP + P - Group 7: ES + TP - Group 8: ES + TP + P Parameters: The eye blink reflex Vibrissae orientation and movement Post-injury duration: 13 weeks | ES of the proximal nerve stump most effectively accelerated the initiation of functional recovery. ES or TP treatments enhanced recovery of some functional parameters more than P treatment. A combinatorial treatment strategy of using ES and TP together promises to be an effective therapeutic intervention for promoting regeneration following facial nerve injury. |
Hetzler et al., 2008 [32] | Sprague -Dawley rats, male | Crush | Type: implantable stimulation device (two Teflon coated wires) Duration: post–crush injury day 1 and daily for 30 min until complete recovery Set to generate pulses every 2 msec for 5-msec duration Location: The right facial nerve, proximal to the crush injury | Rats were randomly assigned to four groups: - Group 1: control (n = 9) - Group 2: crush injury + ES (n = 8) - Group 3: crush injury + TP (n = 8) - Group 4: crush injury + ES + TP (n = 6) Parameters: Vibrissae orientation/movement Semi eye blink, and full eye blink. Post-injury duration: measured until complete recovery. | Complete recovery time was significantly reduced with concurrent ES and TP administration. The concurrent use of two existing treatment methods, electrical stimulation and gonadal steroid treatment, may potentially enhance nerve regeneration and expedite the time required for full functional recovery. |
Lal et al., 2008 [33] | Sprague -Dawley rats, male | Crush | Type: implantable stimulation device (two Teflon coated wires) Duration: post–crush injury day 1 and daily for 30 min until complete recovery. Set to generate pulses every 2 msec for 5-msec duration Location: The right facial nerve, proximal to the crush injury | Rats were randomly assigned to two groups: - Group 1: crush injury + sham stimulation (n = 9) - Group 2: crush injury + ES (n = 8) Parameters: Eye blink reflex Vibrissae orientation Vibrissae movement. Post-injury duration: measured until complete recovery. | ES initiated and accelerated facial nerve recovery in the rat model. |
Non-effective results by ES | |||||
Raslan et al., 2019 [34] | Wistar Unilever rats, female | Transection of femoral and facial nerve The nerves were repaired by end-to-end suturing. | Type: implantable stimulation device (two Teflon coated wires) Duration: BES (1 h, 20 Hz) of the proximal nerve stump Location: - A stainless steel wire (50 μm thick) - both proximal femoral and facial nerve stump were electrically stimulated for 1 h (0.1 ms width, 20 Hz). | The animals were divided into four groups: - Group 1: sham-stimulated (SS) with femoral transection (n = 8) - Group 2: ES group with femoral nerve transection (n = 10) - Group 3: SS with facial nerve transection (n = 9) - Group 4: ES group with facial nerve transection (n = 10) Parameters: Video recordings were performed for gait analysis Whisker motion analysis Post-injury duration: 20 weeks | BES enhances sensory neuron reinnervation after femoral nerve injury, which may in turn, and in addition to direct effects on motor axon regeneration, promote restoration of motor function. However, BES did not improve the functional outcome of facial nerve injury as estimated by vibrissal motion analysis at 8 weeks after injury. |
Sinis et al., 2009 [35] | Wistar rats | Transection | Type: acupuncture needle electrodes. Duration: The muscles were stimulated for 5 min by applying square 0.1 ms pulses at suprathreshold amplitudes (typically 3.0–5.0 V) ES of the vibrissal muscles 3 times a week over 2 months. Location: two acupuncture needle electrodes were inserted towards the levator labii superioris | The animals were divided into six groups (n = 16 in each group): - Group 1: control - Group 2: FFA only - Group 3: Resection - Group 4: FFA + SS - Group 5: FFA + ES - Group 6: FFA + mechanical stimulation Parameters: Video recordings were performed for vibrissal motor performance Degree of collateral axonal branching The number of motor endplates The quality of the reinnervation Post-injury duration: 2 months | ES did not improve functional outcome, but rather reduced the number of innervated motor endplates to approximately one-fifth of normal values and failed to reduce the proportion of poly-innervated motor endplates. ES is not beneficial for recovery of whisker function after facial nerve repair in rats. |
Author | Diseases/Etiology | Design | Stimulation Methods | Experimental Design | Results/Conclusion/Suggestions |
---|---|---|---|---|---|
Effective results by electrical stimulation (ES) | |||||
Mäkelä et al., 2021 [36] | Bell’s palsy, Ramsay Hunt sndrome, and sequelae of temporomandibular joint replacement | 15 patients with acute facial nerve palsy palsy. | Type: transcutaneous electrodes Duration: a biphasic square wave with symmetric positive and negative phases of equal width using phase duration of 0.4 ms and 250 Hz pulse Location: the zygomatic branch of the facial nerve. One electrode was attached just lateral to the orbital rim and the other at approximately 0.5 cm distance laterally. | Day 1: a two-hour TV watching session in which an electrically induced blink was delivered every 5 s. Day 2: TV watching session without electrically induced blinking. The two conditions were counterbalanced. Parameters: Subjective ocular symptoms (Dry Eye Questionnaire ) Visual acuity (Logarithm of the Minimum Angle of Resolution) | Adverse event: not specified The stimulation produced a blink in 8 participants (53%). Electrically elicited blink is a promising method for reducing the eye symptoms in individuals with acute facial nerve palsy |
Kim et al., 2016 [17] | Bell’s palsy (mild-to-moderate grade) | Prospective randomized study | Type: transcutaneous electrodes Duration: Sub-threshold, continuous, low-frequency-impulse electrical stimulation (SCLES) at 20 Hz keep contining ES after 2 months from onset of facial palsy Location: The surface electrode was placed on the main branch of the facial nerve at the tragal pointer as a cathode, and on the intra-temporal area around the stylomastoid foramen as an anode | - Group 1: medical treatment only (n = 30) - Group 2: medical treatment + SCLES (n = 30) Parameters: Change of facial function (House-Brackmann and Sunnybrook scales) | Adverse event: Contact dermatitis (13.3%; 4/30) oral-ocular synkinesis (3.3%; 1/30) Facial function of Group 2 was regained completely within 10.73 ± 5.7 weeks after the onset of facial palsy, and the Group 1 recovered within 13.4 ± 6.0 weeks. The overall rate of patient recovery among those in Group 2 (96%) was significantly higher than the rate among those in Group 1 (p < 0.05). The drug regimen plus SCLES was more effective in treating Bell’s palsy than the conventional drug treatment alone. |
Frigerio et al., 2015 [37] | Bell’s palsy, Lyme disease, Ramsay Hunt syndrome, temporal bone fracture, autoimmune disease Acute unilateral facial paralysis, House-Brackmann grades 4-6. | Prospective, double-blinded, randomized, placebo-controlled study. | Type: transcutaneous electrodes Duration: 0.4- to 1-ms pulse width, 100 to 150 Hz, and 1 to 15 mA. Bipolar, charge-alanced pulse Location: The cathode was positioned 1 cm lateral to the orbital rim. The anode was moved in an arc around the cathode, spanning 90 degrees (30 degrees above to 60 degrees below the cathode) in 10-degree increment | - Group 1: eye blink group (n = 16) by initial ES - Group 2: incomplete eye blink group (n = 12) by initial ES - Group 3: no motor response group (n = 4) by initial ES Parameters: Complete eye closure (Full blink) Synkinesis cutaneous sensation (Wong-Baker Faces Pain Rating Scale) Average current of initial eye twitch, complete closure | Adverse event: Synkinesis (34.3%; 11/32) Complete eye closure was achieved in 12 weeks later (n = 32) - Group 1: 75% (12/16) - Group 2: 25% (3/12) - Group 3: 50% (2/4) Complete eye closure was achieved in 12 months later (n = 20) - Group 1: 83% (5/6) - Group 2: 50% (5/10) - Group 3: 50% (2/4) Transcutaneous facial nerve stimulation may artificially elicit eye blink in a majority of patients with acute facial paralysis. |
Tuncay et al., 2015 [16] | Bell’s palsy. | Prospective randomized study | Type: transcutaneous electrodes Duration: monophasic waveform 100 ms of pulse duration, 300 ms of interpulse interval, and a pulse rate of 2.5 Hz ES was performed 5 days per week for 3 weeks. Location: 11 facial muscles (frontalis, corrugator supercilii, palpebral part of orbicularis oculi, levator labii superioris alaeque nasi, levator labii superioris, levator anguli oris, risorius, orbicularis oris, depressor anguli oris, depressor labii inferioris, and levator menti) | - Group 1: control group, oral steroids + conventional therapy only (n = 28) - Group 2: oral steroids + conventional therapy + ES (n = 32) Conventional therapy: hot pack, facial expression exercises, and massage Parameters: House-Brackmann scale Facial disability index latency and amplitude of CMAPs | Adverse event: not specified The addition of 3 weeks of daily ES after facial palsy onset (4 weeks) improved functional facial movements and electrophysiologic outcome measures at 3-month follow-up in patients with Bell’s palsy. |
Targan et al., 2000 [38] | Chronic facial nerve injury caused by Bell’s palsy, acoustic neuroma excision. | Case control study | Type: transcutaneous electrodes Duration: a monophasic current waveform, pulse duration of 86 μs, and delivered 1 pulse every 700 ms. Location: orbicularis oculi, frontalis, zygomatic, and nasalis were stimulated with submotor level intensity For 30 min daily during the first month, 1 h daily during the second month, and 2 h daily during the third month. for 6 h while sleeping at night during the fourth month. buccinator, mentalis, orbicularis oris, and mandibularis were stimulated for 30 min (fifth month) and 60 min (sixth month) daily. | - Group 1: Bell’s palsy (n = 12) - Group 2: acoustic neuroma excision (n = 5) Parameters: House-Brackmann score Motor nerve conduction latency Clinical residuals score | A 6-month program of electrical stimulation partially reverses chronic deficiencies in motor conduction latencies and clinical residuals and may prove beneficial to patients with chronic facial nerve paresis. |
Gittins et al., 1999 [39] | Chronic, moderate to severe facial nerve palsy with acoustic neuroma resection, Ramsay Hunt syndrome. | Case control study | Type: transcutaneous electrodes Duration: a monophasic current waveform, pulse frequency and width were set to 10 Hz and 200 microsec Location: medial and lateral canthi | - Group 1: normal control (n = 30) - Group 2: chronic, moderate to severe facial nerve palsy (n = 10) Parameters: Voluntary and spontaneous eyelid movement and lid velocity | The use of transcutaneous electrical nerve stimulators over a period of three months results in a significant improvement in voluntary eyelid movements by reducing the stiffness of the eyelid mechanics. |
Non-effective results by ES | |||||
Shoman et al., 2022 [40] | Bell’s palsy | Prospective, randomized, single-blind, controlled study | Type: transcutaneous electrodes Duration: -LLLT: A total of 12 LLLT sessions (twice per week over six weeks). Each session lasted 8 min (1min/point) for 8 points. -ES: 0.1 ms to 1 ms and a frequency of 50 Hz. A total of 12 ES sessions (twice per week over six weeks). Location: - LLLT: upper branch, middle, lower branch, nerve trunk of facial nerve, orbicularis oris muscle, muscles of the nose, levators of the upper lip, and depressors of the lower lip. -ES: one electrode on the nerve trunk in front of the ear, while the other electrode was placed on the stimulated muscle (the frontalis and nasalis muscles) | - Group 1 (n = 15): low-level laser therapy (LLLT) - Group 2 (n = 15): ES - Group 3 (n = 15): control Parameters: Compound muscle action potentials (CMAPs) Latency of nerve action potential Sunnybrook facial grading system | Adverse event: not specified Short-term investigation revealed that LLLT was more efficient than ES in facial nerve regeneration for patients with Bell’s palsy. There was no statistically significant difference between Group 2 and 3. |
Puls et al., 2020 [41] | Facial paralysis caused by surgical removal of benign or malignant tumor. Hypoglossal-facial-jump anastomosis (HFJA) in the last 12 years were selected | Retrospective study. | Type: transcutaneous electrodes Duration: biphasic triangular, 110 ms of pulse duration (twice per day for 10 min, 5 days per week) Location: zygomaticus muscle, depressor anguli oris muscle, and depressor labii muscle. | Experiment 1 (HFJA) - Group 1: only surgery (n = 33) - Group 2: surgery + ES (n = 6) Parameters: rate of reinnervation by needle eletromyography Experiment 2 (no HFJA) - Group 1: control (n = 7) - Group 2: ES (n = 6) Parameters: Sunnybrook score eFACE score | Adverse event: no No difference in time of reinnervation after facial nerve reconstruction surgery was observed between patients who did and did not receive ES. After spontaneous reinnervation, less synkinesis was noted. There was no evidence that ES prevents or delays reinnervation or increases synkinesis in facial paralysis. |
Alakram et al., 2010 [15] | Bell’s palsy (less than 30 days post onset) | Prospective randomized study. | Type: transcutaneous electrodes Duration: a pulsed setting and frequency of 10 Hz, a pulse width/duration of 10 ms Location: frontalis or obicularis oculi, zygomaticus major (motor point 10 min, total 30 min) | - Group 1: control group, conventional therapy (n = 8) - Group 2: conventional therapy + transcutaneous electrical stimulation (TENS, n = 8) Parameters: Facial Disability Index | During the acute phase of Bell’s palsy, the clinical effects of electrical stimulation were noticeable but did not reach statistical significance. |
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Yoo, M.C.; Kim, J.H.; Kim, Y.J.; Jung, J.; Kim, S.S.; Kim, S.H.; Yeo, S.G. Effects of Electrical Stimulation on Facial Paralysis Recovery after Facial Nerve Injury: A Review on Preclinical and Clinical Studies. J. Clin. Med. 2023, 12, 4133. https://doi.org/10.3390/jcm12124133
Yoo MC, Kim JH, Kim YJ, Jung J, Kim SS, Kim SH, Yeo SG. Effects of Electrical Stimulation on Facial Paralysis Recovery after Facial Nerve Injury: A Review on Preclinical and Clinical Studies. Journal of Clinical Medicine. 2023; 12(12):4133. https://doi.org/10.3390/jcm12124133
Chicago/Turabian StyleYoo, Myung Chul, Jeong Hee Kim, Yong Jun Kim, Junyang Jung, Sung Soo Kim, Sang Hoon Kim, and Seung Geun Yeo. 2023. "Effects of Electrical Stimulation on Facial Paralysis Recovery after Facial Nerve Injury: A Review on Preclinical and Clinical Studies" Journal of Clinical Medicine 12, no. 12: 4133. https://doi.org/10.3390/jcm12124133
APA StyleYoo, M. C., Kim, J. H., Kim, Y. J., Jung, J., Kim, S. S., Kim, S. H., & Yeo, S. G. (2023). Effects of Electrical Stimulation on Facial Paralysis Recovery after Facial Nerve Injury: A Review on Preclinical and Clinical Studies. Journal of Clinical Medicine, 12(12), 4133. https://doi.org/10.3390/jcm12124133