Christopher J. Knox

The effect of electrical and mechanical stimulation on the regenerating rodent facial nerve

Investigators have long sought realistic methods to accelerate regeneration following nerve injury. Herein, we investigated the degree to which manual target muscle manipulation and brief electrical stimulation of the facial nerve, alone or in combination, affects recovery following rat facial nerve injury.

Good correlation between original and modified House Brackmann facial grading systems.

Subjective scales of facial function were plagued with reporting variations until the House‐Brackmann scale was described in 1985. Despite its utility, weaknesses were identified, including noninclusion of synkinesis phenomena and insensitivity to segmental weakness. Therefore, the scale was recently revised to address these weaknesses. The objective of this investigation was to determine agreement between the original and the updated House‐Brackmann scales.

Facial nerve repair: fibrin adhesive coaptation versus epineurial suture repair in a rodent model

Repair of the transected facial nerve has traditionally been accomplished with microsurgical neurorrhaphy; however, fibrin adhesive coaptation (FAC) of peripheral nerves has become increasingly popular over the past decade. We compared functional recovery following suture neurorrhaphy to FAC in a rodent facial nerve model.

The convergence of facial nerve branches providing whisker pad motor supply in rats: Implications for facial reanimation study

Rodent whisking behavior is supported by the buccal and mandibular branches of the facial nerve, but a description of how these branches converge and contribute to whisker movement is lacking.

Functional recovery after facial nerve cable grafting in a rodent model.

IMPORTANCE Cable grafting is widely considered to be the preferred alternative to primary repair of the injured facial nerve; however, quantitative comparison of the 2 techniques has not been previously undertaken in a rodent model. OBJECTIVE To establish functional recovery parameters after interposition autografting in a rodent facial nerve model. DESIGN, SETTING, AND PARTICIPANTS Prospective randomized animal study at a tertiary care facial nerve center using 16 female Wistar Hannover rats. INTERVENTION The experimental group received reversed autograft reconstruction of a 20-mm neural gap, and the control group received facial nerve transection and primary repair. MAIN OUTCOME AND MEASURE Whisker excursion was measured weekly for 70 postoperative days using laser micrometers. RESULTS The control group exhibited the most rapid recovery, with substantial return of whisker movement occurring during the third postoperative week. The experimental group demonstrated return of function beginning in the fourth postoperative week, eventually achieving a degree of function comparable to that of the control group by the sixth postoperative week (P = .68). CONCLUSIONS AND RELEVANCE Recovery of facial function after cable grafting seems to be slower than, but eventually similar to, recovery after primary neurorrhaphy in a rodent model. In the present study we have established a benchmark for recovery of whisker movement across a 20-mm rodent facial nerve gap, which will be used for comparison of different facial nerve gap bridging materials in future studies. LEVEL OF EVIDENCE NA.

Bilateral Facial Paralysis: A 13-Year Experience.

Background: Bilateral facial palsy is a rare clinical entity caused by myriad disparate conditions requiring different treatment paradigms. Lyme disease, Guillain-Barré syndrome, and leukemia are several examples. In this article, the authors describe the cause, the initial diagnostic approach, and the management of long-term sequelae of bilateral paralysis that has evolved in the authors’ center over the past 13 years. Methods: A chart review was performed to identify all patients diagnosed with bilateral paralysis at the authors’ center between January of 2002 and January of 2015. Demographics, signs and symptoms, diagnosis, initial medical treatment, interventions for facial reanimation, and outcomes were reviewed. Results: Of the 2471 patients seen at the authors’ center, 68 patients (3 percent) with bilateral facial paralysis were identified. Ten patients (15 percent) presented with bilateral facial paralysis caused by Lyme disease, nine (13 percent) with Möbius syndrome, nine (13 percent) with neurofibromatosis type 2, five (7 percent) with bilateral facial palsy caused by brain tumor, four (6 percent) with Melkersson-Rosenthal syndrome, three (4 percent) with bilateral temporal bone fractures, two (3 percent) with Guillain-Barré syndrome, one (2 percent) with central nervous system lymphoma, one (2 percent) with human immunodeficiency virus infection, and 24 (35 percent) with presumed Bell palsy. Treatment included pharmacologic therapy, physical therapy, chemodenervation, and surgical interventions. Conclusions: Bilateral facial palsy is a rare medical condition, and treatment often requires a multidisciplinary approach. The authors outline diagnostic and therapeutic algorithms of a tertiary care center to provide clinicians with a systematic approach to managing these complicated patients.

The Effects of Potential Neuroprotective Agents on Rat Facial Function Recovery Following Facial Nerve Injury

Objective. To evaluate whether a series of pharmacologic agents with potential neuroprotective effects accelerate and/or improve facial function recovery after facial nerve crush injury. Study Design. Randomized animal study. Setting. Tertiary care facility. Methods. Eighty female Wistar-Hannover rats underwent head restraint implantation and daily conditioning. Animals then underwent unilateral crush injury to the main trunk of the facial nerve and were randomized to receive treatment with atorvastatin (n = 10), sildenafil (n = 10), darbepoetin (n = 20), or a corresponding control agent (n = 40). The return of whisking function was tracked throughout the recovery period. Results. All rats initiated the return of whisking function from nerve crush by day 12. Darbepoetin-treated rats (n = 20) showed significantly improved whisking amplitude and velocity across the recovery period, with several days of significant pairwise differences vs comparable control rats (n = 16) across the first 2 weeks of whisking function return. In contrast, rats treated with sildenafil (n = 10) and atorvastatin (n = 10) did not show significant improvement in whisking function recovery after facial nerve crush compared to controls. By week 8, all darbepoetin-treated animals and comparable nerve crush control animals fully recovered whisking function and were statistically indistinguishable. Conclusion. Among the 3 potentially neuroprotective agents evaluated, only darbepoetin administration resulted in accelerated recovery of whisking parameters after facial nerve crush injury. Further efforts to define the mechanism of action and translate these findings to the use of darbepoetin in the care of patients with traumatic facial paralysis are needed.

Rat whisker movement after facial nerve lesion: evidence for autonomic contraction of skeletal muscle.

Vibrissal whisking is often employed to track facial nerve regeneration in rats; however, we have observed similar degrees of whisking recovery after facial nerve transection with or without repair. We hypothesized that the source of non-facial nerve-mediated whisker movement after chronic denervation was from autonomic, cholinergic axons traveling within the infraorbital branch of the trigeminal nerve (ION). Rats underwent unilateral facial nerve transection with repair (N=7) or resection without repair (N=11). Post-operative whisking amplitude was measured weekly across 10weeks, and during intraoperative stimulation of the ION and facial nerves at ⩾18weeks. Whisking was also measured after subsequent ION transection (N=6) or pharmacologic blocking of the autonomic ganglia using hexamethonium (N=3), and after snout cooling intended to elicit a vasodilation reflex (N=3). Whisking recovered more quickly and with greater amplitude in rats that underwent facial nerve repair compared to resection (P<0.05), but individual rats overlapped in whisking amplitude across both groups. In the resected rats, non-facial-nerve-mediated whisking was elicited by electrical stimulation of the ION, temporarily diminished following hexamethonium injection, abolished by transection of the ION, and rapidly and significantly (P<0.05) increased by snout cooling. Moreover, fibrillation-related whisker movements decreased in all rats during the initial recovery period (indicative of reinnervation), but re-appeared in the resected rats after undergoing ION transection (indicative of motor denervation). Cholinergic, parasympathetic axons traveling within the ION innervate whisker pad vasculature, and immunohistochemistry for vasoactive intestinal peptide revealed these axons branching extensively over whisker pad muscles and contacting neuromuscular junctions after facial nerve resection. This study provides the first behavioral and anatomical evidence of spontaneous autonomic innervation of skeletal muscle after motor nerve lesion, which not only has implications for interpreting facial nerve reinnervation results, but also calls into question whether autonomic-mediated innervation of striated muscle occurs naturally in other forms of neuropathy.

Long-Term Functional Recovery after Facial Nerve Transection and Repair in the Rat

BACKGROUND The rodent model is commonly used to study facial nerve injury. Because of the exceptional regenerative capacity of the rodent facial nerve, it is essential to consider the timing when studying facial nerve regeneration and functional recovery. Short-term functional recovery data following transection and repair of the facial nerve has been documented by our laboratory. However, because of the limitations of the head fixation device, there is a lack of long-term data following facial nerve injury. The objective of this study was to elucidate the long-term time course and functional deficit following facial nerve transection and repair in a rodent model. METHODS Adult rats were divided into group 1 (controls) and group 2 (experimental). Group 1 animals underwent head fixation, followed by a facial nerve injury, and functional testing was performed from day 7 to day 70. Group 2 animals underwent facial nerve injury, followed by delayed head fixation, and then underwent functional testing from months 6 to 8. RESULTS There was no statistical difference between the average whisking amplitudes in group 1 and group 2 animals. CONCLUSION Functional whisking recovery 6 months after facial nerve injury is comparable to recovery within 1 to 4 months of transection and repair, thus the ideal window for evaluating facial nerve recovery falls within the 4 months after injury.

Quantitative Analysis of Muscle Histologic Method in Rodent Facial Nerve Injury

OBJECTIVE To describe denervation features of facial musculature following facial nerve injury in a rodent model. METHODS Six Wistar-Hannover rats underwent unilateral transection and immediate repair of the facial nerve. After 8 weeks, muscular bundles consisting of dilator naris and levator labii superioris from both sides were analyzed for mean muscle cell diameter and the percentage of muscle cell cross-sectional area using image processing software. The atrophic features of facial muscles were quantified and compared with the contralateral, healthy side of the face. RESULTS Weekly postoperative whisking assessment demonstrated the anticipated course of recovery. We observed significant differences between the normal side and the manipulated side, respectively, in the percentage of muscle specimen cross-sectional area attributable to muscle cell profiles (57% vs 29%; P = .006) and total fiber counts (1346 vs 794; P = .02). The mean cross-sectional area of individual muscle fibers was higher on the normal side (1129 vs 928 μm2; P = .39); however, this difference was statistically nonsignificant. CONCLUSION The objective, quantitative measures of muscle microstructure used in this report provide a valuable point of comparison for whisking function and electrophysiologic measures and can be used in future studies to assess muscle atrophic features associated with facial nerve injury and repair techniques.