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JNNP Online First, published on September 16, 2014 as 10.1136/jnnp-2014-308465 Neurosurgery
RESEARCH PAPER
Hypoglossal–facial nerve ‘side’-to-side neurorrhaphy using a predegenerated nerve autograft for facial palsy after removal of acoustic tumours at the cerebellopontine angle Liwei Zhang,1 Dezhi Li,1 Hong Wan,2 Shuyu Hao,1 Shiwei Wang,2 Zhen Wu,1 Junting Zhang,1 Hui Qiao,2 Ping Li,2 Mingran Wang,2 Diya Su,2 Michael Schumacher,3 Song Liu1,2,3 ▸ Additional material is published online only. To view please visit the journal online (http://dx.doi.org/10.1136/ jnnp-2014-308465). 1
Department of Neurosurgery and China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China 2 Beijing Neurosurgical Institute and Beijing Key Laboratory of Central Nervous System Injury, Capital Medical University, Beijing, China 3 UMR 788, INSERM and Université Paris-Sud, Le Kremlin-Bicêtre, France Correspondence to Dr Song Liu, UMR 788, INSERM et Université ParisSud, 80 rue du Général Leclerc, Le Kremlin-Bicêtre Cedex 94276, France; [email protected] LZ, DL and HW contributed equally to this study. Received 7 May 2014 Revised 7 August 2014 Accepted 28 August 2014
ABSTRACT Trial design Hypoglossal–facial nerve (HN–FN) neurorrhaphy is a method commonly used to treat facial palsy when the proximal stump of the injured FN is unavailable. Since the classic HN–FN neurorrhaphy method that needs to section the injured FN is not suitable for incomplete facial palsy, we investigated a modified method that consists of HN–FN ‘side’-to-side neurorrhaphy, retaining the remaining or spontaneously regenerated FN axons while preserving hemihypoglossal function. Methods To improve axonal regeneration, we used for the first time a predegenerated sural autograft for performing HN–FN ‘side’-to-side neurorrhaphy followed by postoperative facial exercise. We treated 12 patients who had experienced FN injury for 1–18 months as a result of acoustic tumour removal. All patients experienced facial grade V–VI paralysis according to the House-Brackmann scale, but their FN was anatomically preserved. No spontaneous facial reinnervation was detected before repair. Results Although we did not perform fresh nerve grafts and HN–FN ‘side’-to-end neurorrhaphy as controls for ethical reasons, the reparative outcomes after nerve reconstruction were remarkable: functional improvements were detected as soon as 3 months after repair, HouseBrackmann grade II or III FN functions were achieved in five and four patients, respectively, and there were no apparent signs of synkinesis. The three patients who experienced less satisfactory outcomes had exhibited facial palsy for more than 1 year accompanied by muscle atrophy, consistent with a need for rapid surgical intervention. Conclusions Based on fundamental concepts and our experimental results, this new surgical method represents a major advance in the rehabilitation of FN injury. Trial registration number JS2013-001-02.
INTRODUCTION To cite: Zhang L, Li D, Wan H, et al. J Neurol Neurosurg Psychiatry Published Online First: [please include Day Month Year] doi:10.1136/jnnp2014-308465
Facial palsy due to facial nerve (FN) injury results in facial disfigurement and the inability to express emotions with severe psychological impact for patients.1 FN injury is commonplace in accidents or cerebellopontine angle (CPA) surgery.2 In addition, FN dysfunction can result from diseases, and
approximately 20% of Bell’s palsy patients experience permanent damage.3 Surgical transposition of the hypoglossal nerve (HN) is the most commonly used procedure for innervating the FN distal stump.2 Since classic HN–FN end-to-end neurorrhaphy causes serious neurological deficits resulting from the sacrifice of the HN, surgical interventions have been improved by transferring half of the HN to the injured FN, either directly or via a nerve graft.4 However, clinical outcomes remain unsatisfactory and the postoperative recovery period is very long, sometimes beyond 2 years. Thus, regenerative therapies represent an important challenge. Two major obstacles most likely contribute to the poor reparative outcomes: a long waiting period before repair surgery, resulting in unfavourable changes in the injured FN and atrophy of its target muscles,5 and a cellular environment poorly supportive of nerve regeneration.2 6 7 Waiting for spontaneous recovery before repair surgery is indeed associated with a reduced benefit of treatment outcome. On the other hand, as the conventional HN–FN neurorrhaphy methods require sectioning of the injured FN, performing early surgery prevents spontaneous reinnervation of the spared FN axons, which is not particularly suitable for the case whose injured FN is anatomically preserved undergoing persistent incomplete facial paralysis or potential spontaneous reinnervation. In a rat model of persistent incomplete facial paralysis, we have recently demonstrated that rapid reinnervation of the whisker pad can be achieved by the HN–FN ‘side’-to-side neurorrhaphy using an interpositional nerve autograft with preservation of the injured FN.8 Thus, this method may be rapidly performed on patients without compromising the spontaneous reinnervation by the remaining FN axons. Most importantly, we used predegenerated nerve grafts (PNG) in our experiments to provide a supportive environment for axonal regeneration. The nerve graft was prepared by sectioning the peroneal nerve and using its distal segment 1 week later.8 9 This procedure is based on the concept that Schwann cells transdifferentiate into repair cells distal to the nerve injury site, thus providing a permissive environment for axon
L, etemployer) al. J Neurol Neurosurg 2014;0:1–8. doi:10.1136/jnnp-2014-308465 Copyright Article author (orZhang their 2014.Psychiatry Produced by BMJ Publishing Group Ltd under licence.
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Neurosurgery regrowth.10–12 However, the use of in vivo PNG has so far been considered as unfeasible in clinical practice.13 We report 12 patients with FN injury treated with the HN– FN ‘side’-to-side neurorrhaphy using a PNG. Six other patients who did not receive the neurorrhaphy served as controls. Their FNs were injured during the CPA surgery for removing acoustic tumours, but were anatomically preserved. All the patients experienced grade V–VI facial paralysis on the House-Brackmann (H-B) scale without any clinically apparent spontaneous reinnervation for a period of 1–18 months postinjury.14
SUBJECTS AND METHODS Between December 2010 and May 2012 in our neurosurgical centre at Beijing Tiantan Hospital, 12 patients (8 men, 4 women) who experienced unilateral facial paralysis due to acoustic tumour resection in the CPA underwent the HN–FN ‘side’-to-side neurorrhaphy using a PNG followed by a postoperative facial exercise. Six other patients (1 man, 5 women) did not receive the repair surgery but facial exercise at home, serving as controls. The age of the patients ranged from 22 to 65 years (mean 39 years). The time from the onset of paralysis to repair treatment ranged from 1 to 24 months (mean 7.3 months). All patients exhibited H-B grade V–VI facial paralysis without any clinical evidence of functional improvement before the repair treatment. Table 1 shows the H-B scale,14 and table 2 presents the general clinical data of the 18 patients. For the repair treatment with the HN–FN ‘side’-to-side neurorrhaphy and/or facial exercise, patients were informed about various aspects of their treatment, including its advantages and trade-offs.
Predegeneration of the sural nerve Predegeneration was performed by injuring the sural nerve 1 week prior to the repair surgery. Briefly, an incision of 3 cm length was performed in patients on the ipsilateral lower leg of the paralysed face side at approximately 10 cm above the midpoint of the lateral malleolus and the Achilles tendon under local anaesthesia using 2% lidocaine. After being exposed, the whole sural nerve was seriously and completely compressed one time by a pair of haemostat pliers to section the axons contained in the sural nerve, but to preserve the nerve in continuity by its epineurium, commensurate with an approximate Sunderland grade III
Table 1 House-Brackmann facial nerve grading system (House and Brackmann, 1985)
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Grade
Description
Characteristics
I II
Normal Mild dysfunction
III
Moderate dysfunction
IV
Moderately severe dysfunction
V
Severe dysfunction
VI
Total paralysis
Normal facial function Gross: slight weakness on close inspection; may have very slight synkinesis. At rest: normal symmetry and tone Gross: obvious but not disfiguring difference between the two sides; noticeable but not severe synkinesis, contracture and/or hemifacial spasm. At rest: normal symmetry and tone Gross: obvious weakness and/or disfiguring asymmetry. At rest: normal symmetry and tone Gross: only barely perceptible motion. At rest: asymmetry No movement
injury. The damage result was verified under a surgical microscope during the surgical operation, confirming that the contained tissues were approximately sectioned with a distance of the tweezers’ tip except its epineurium. The main objective of this procedure was to create axonal degeneration in the distal segment of the sural nerve, thus stimulating the proliferation of the contained Schwann cells. In order to identify the injury site and limit axon spontaneous regeneration into the distal segment, the sural nerve was also ligated using a 6-0 nylon suture at the lesion site. The incision was then closed in layers using 4-0 nylon sutures. The patients were discharged immediately for a 1-week period. The day of repair surgery, the distal segment of the injured sural nerve was removed approximately 8 cm in length as the PNG.
Repair surgery The HN–FN ‘side’-to-side neurorrhaphy was performed identically on patients under general anaesthesia in a supine position with the head rotated towards the unaffected side. For the use of the term HN–FN ‘side’-to-side neurorrhaphy, the ‘side’ placed between quotation marks indicates that half of the HN was sectioned at the PNG bridging site and the side without quotation marks refers to laterally suturing the PNG to the injured FN without sectioning its main trunk, being different from a true end-to-side or side-to-side neurorrhaphy, because the injured hypoglossal axons can still regenerate down the original hypoglossal nerve pathway and axonal regrowth probably also occurs across a supercharged side-to-side nerve neurorrhaphy. A lazy S-shaped skin incision approximately 8 cm in length was performed from the anterior edge of the earlobe extending down the upper neck along the anterior edge of the sternocleidomastoid muscle to the level of the hyoid bone. The external jugular vein and the great auricular nerve were preserved. Figure 1 illustrates the HN–FN ‘side’-to-side neurorrhaphy procedure. Under an operating microscope, the FN was carefully exposed and dissected to free its distal portion at the two main branches in the parotid gland. The HN was exposed after posteriorly retracting the posterior belly of the digastric muscle and confirmed using a nerve stimulator. Intraoperative electrophysiological tests to record compound muscle action potentials (CMAPs) with direct nerve electrostimulation were performed for detecting the injured FN function and identifying the HN. One half of the HN was then cross-sectioned at a site closely distal to the descendens hypoglossi in order to avoid compromising sufficient glottis innervation. The proximal extremity of the PNG was surgically bridged end-to-‘side’ to the HN at the partial cross-section site via 6–8 stitches using 10-0 nylon sutures (figure 1A). An epineural window was created by using microsurgical scissors on the exposed FN at each of the two main branches. The two distal extremities of the PNG were created and then bridged to the two main FN branches end-to-side at each of the epineural windows via 3–4 stitches using 10-0 nylon sutures(figure 1B). The surgical wound was then sutured in two layers over a suction tube that was removed after 48 h. The patients were discharged 3 days after the repair surgery.
Facial exercise programme A daily facial exercise programme was initiated in the 12 surgical treatment patients 1 week after the repair surgery and in the six control patients immediately after the first consultation. The facial exercise programme included facial passive motion and massage with the aim of moving the paralysed facial muscles, such as passive eye closing, cheek drumming, brow lifting, etc, Zhang L, et al. J Neurol Neurosurg Psychiatry 2014;0:1–8. doi:10.1136/jnnp-2014-308465
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Neurosurgery Table 2 Clinical data and treatment outcome
Patient
H-B grade initial
Duration of facial paralysis (months)
Treatment
Follow-up period (months)
Case 1 Case 2 Case 3 Case 4 Case 5 Case 6 Case 7 Case 8 Case 9 Case 10 Case 11 Case 12 Contro 1 Contro 2 Contro 3 Contro 4 Contro 5 Contro 6
VI VI V VI VI VI V VI V V VI VI V VI VI V VI V
18 19 6 4 13 1 6 5 6 6 3 4 3 6 4 2 2 24
Surgery+exercise Surgery+exercise Surgery+exercise Surgery+exercise Surgery+exercise Surgery+exercise Surgery+exercise Surgery+exercise Surgery+exercise Surgery+exercise Surgery+exercise Surgery+exercise Exercise Exercise Exercise Exercise Exercise Exercise
43 39 38 35 35 35 35 32 32 30 27 25 22 20 19 20 19 16
and sometimes with the help of the patient’s fingers. We advised patients to perform the facial exercise in front of a mirror more than three times daily for at least 30 min each time. For the 12 surgical treatment patients, appropriate tongue exercise was recommended when the first signal of hypoglossal innervation in the paralysed face was detected.
Evaluation of facial reanimation and tongue movement FN function was assessed regularly using the H-B grading scale before and at 3, 6 and 9 months and beyond after the repair treatment. Each patient was also photographed and videotaped to record any changes in facial symmetry and motion. Tongue atrophy and deviation were examined according to a scale proposed by Martins et al.15
Electrophysiological examination Electromyography was performed to evaluate the electrical activity produced by the facial muscles before and after repair treatment.16 Intact muscle tissue at rest is electrically inactive, but denervated muscle produces spontaneous electrical activity that is referred to as fibrillation. In contrast, a disorderly group of action potentials with varying rates and amplitudes should appear when an innervated muscle is voluntarily contracted. Therefore, we measured the spontaneous activity of the paralysed facial muscles at rest and recorded muscle action potentials during muscle movement. Potential recordings were performed on the orbicularis oculi, orbicularis oris and tongue muscle. CMAPs were recorded in the orbicularis oculi and orbicularis oris while transcutaneously electrostimulating the FN in the mastoid area or the mandibular angle. Simultaneously, the F wave was also recorded. This is one of the late responses produced by the antidromic activation of motoneurons via supramaximal stimulation of the nerve trunk, indicating nerve conduction from the motoneuron cell body to the motor end plate.17 F wave persistence is typically 80–100% (or at least above 50%) in intact muscle.
First sign of innervation after treatment (months)
Facial function evaluation (HB grade) after treatment
3 months
6 months
9 months
Last evaluation
6 6 3 3 6 3 3 3 3 3 3 3 6 6 6 6 6 –
VI VI V V VI V V V V V V V V VI VI V VI V
V V IV IV V IV IV V V IV IV IV IV V V IV V V
V V IV III V III III IV IV IV III III III V V IV V V
V V III II IV II II III III III II II III V V IV IV V
RESULTS All patients were followed up for a mean of 29 months (ranging from 16 to 43 months) after repair treatment. For the 12 surgical treatment patients, postoperative complications were not found during the follow-up period in any of them. The initial anaesthesia of the lateral malleolus region due to ablation and predegeneration of the sural nerve appeared to be insignificant to all the patients. Tongue mobility was not impaired and neither tongue atrophy nor deviation was detected. None of the patients reported difficulty with phonation or swallowing after the neurorrhaphy surgery.
Improvement in FN function Table 2 presents the overall results of FN function for the 18 patients before and after repair treatment. For the 12 surgical treatment patients, eight and four patients, respectively, experienced H-B grade VI and V unilateral facial paralysis before repair surgery. Immediately after the HN–FN ‘side’-to-side neurorrhaphy, no further deficit in FN function was detected in any of the four patients who displayed paralysis of H-B grade V. Slight improvement in FN function was first detected in four of the eight patients who exhibited H-B grade VI facial palsy, such as barely perceptible motion of the paralysed facial muscles, as early as 3 months after repair surgery. At this time point, these four patients improved their FN function from H to B grade VI–V. Six months after the surgery, improvement of the FN function with perceptible facial motion was detected in all the 12 patients. The recovered facial muscle contraction was induced when facial voluntary motion and tongue strong contraction such as lifting the tongue against the palate. They were either slight or strong, indicating varying extents of spontaneous reinnervation by FN axons or innervation by hypoglossal motoneurons. Moreover, five cases recovered facial symmetry and tone at rest. Importantly, synkinesis was not found in the patients during eating, drinking or speaking. At the end of the follow-up period, the extent of FN functional recovery reached
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Neurosurgery of the paralysed facial muscles either during voluntary face contraction or while strongly lifting the tongue against the palate, indicating that the effective innervation of the paralysed facial muscles was established by both facial and hypoglossal motoneurons (see online supplementary video 2). We found that the patient’s recovered facial motion was much stronger when she lifted her tongue against the palate. Her FN function improved to H-B grade IV at 2 years after neurorrhaphy (figure 3). For the six control patients, slight facial voluntary contraction was found after 6 months of facial exercise. No facial contraction was detected during the follow-up period when they strongly lifted their tongue against the palate. Functional improvement of the FN was not evident with time, except for control 1 whose extent of the FN function reached H-B grade III at the end of the follow-up period. Controls 4 and 5 recovered their FN function on H-B grade IV with a return of facial symmetry and tone at rest. Facial asymmetry persisted in the remaining three patients and their FN function remained limited to H-B grade V until the end of the follow-up period (table 2).
Electrophysiological examinations
Figure 1 Schematic drawings showing surgical procedures of the hypoglossal–facial nerve (HN–FN) ‘side’-to-side neurorrhaphy. After exposing the FN and HN, the HN–FN ‘side’-to-side neurorrhaphy was performed through a predegenerated nerve graft (PNG). One end of the PNG was bridged end-to-‘side’ to the HN at the site where approximately 50% of axons were cross-sectioned (A). The other end of the PNG was bridged end-to-side to the distal FN through a window where only the epineurium was removed (B).
H-B grade II in five patients (cases 4, 6, 7, 11, 12; figure 2), grade III in four patients (cases 3, 8, 9, 10), grade IV in one patient (case 5) and grade V in two patients (Cases 1, 2; table 2). In contrast to patients with facial paralysis for less than 6 months, Cases 1, 2 and 5 with facial paralysis for more than 1 year had evident signs of muscle atrophy before repair surgery. For them, beneficial effects of repair surgery were only observed after 6 months. Case 1 did not perform intense facial exercise after the repair surgery, and his facial asymmetry persisted with FN function of H-B grade V until the end of the follow-up period. Case 2 performed intense daily facial exercise and exhibited very prominent motion of the paralysed facial muscles when he strongly lifted his tongue against the palate 1 year after the repair surgery (see online supplementary video 1). In this case, however, only slight motion of the facial muscles was detected during voluntary face contractions, suggesting that the innervation was primarily established by hypoglossal motoneurons. Since the apparent atrophy of his facial muscles did not recover, the disfigurement persisted, and his FN function was limited as H-B grade V despite the return of notable facial motion. Case 5 also performed intense facial exercise during the follow-up period, but exhibited much weaker motion of the paralysed facial muscles 6 months after the neurorrhaphy. One year after the repair surgery, however, the patient recovered detectable motion 4
Before the repair treatment, no CMAPs were detected in all 18 patients when electrostimulating the injured FN trunk at the mastoid area and the mandibular angle. Neither the F wave nor any muscle action potential was recorded at that time. We detected frequent spontaneous electrical activity (fibrillation) in the facial muscles at rest, confirming their denervation. For the 12 surgical treatment patients, CMAPs were detected in all of them when electrostimulating the FN at the mandibular angle but not at the mastoid area 3 months after the HN–FN ‘side’-to-side neurorrhaphy. Simultaneously, the F wave was also recorded, which displayed delayed latency and lower amplitude (figure 4). Muscle action potentials were detected in seven patients (cases 4, 5, 6, 8, 9, 11 and 12) in the orbicularis oris and in five patients (cases 4, 5, 6, 11 and 12) in the orbicularis oculi when they voluntarily contracted their facial muscles, indicating spontaneous reinnervation. Six months after the repair surgery, the muscle action potentials were detected in all patients except case 1, for whom muscle action potentials were detected in the orbicularis oris only after 9 months and in the orbicularis oculi after 12 months. At these time points, we also detected muscle action potentials in the orbicularis oculi and orbicularis oris muscles of the patients when they strongly lifted their tongue against the palate, confirming the innervation of the facial muscles by hypoglossal motoneurons (figure 5). The amplitude of the CMAPs, the F wave and the muscle contraction potentials increased over time in these patients, indicating progressive improvement in FN function. At the end of the follow-up period, only minor fibrillation was detected in the target muscles at rest. The blink reflex did not recover in the patients, except for case 4, for whom it was detected after 9 months postoperatively. For the six control patients, no evident CMAPs and F waves were recorded at any time of the follow-up period when electrostimulating the FN at the mandibular angle and the mastoid area, except for controls 1 and 4 when electrostimulating the FN at the mastoid area after 6 months postfacial exercise. Slight muscle action potentials were detected in the orbicularis oris and/or the orbicularis oculi of these patients when they voluntarily contracted their facial muscles, but none was recorded when their tongue was strongly lifted against the palate at the end of the follow-up period, consistent with the clinical observation.
Zhang L, et al. J Neurol Neurosurg Psychiatry 2014;0:1–8. doi:10.1136/jnnp-2014-308465
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Neurosurgery Figure 2 These pictures were taken from case 4 before repair surgery (left) and 1 year after (right) repair surgery. The left pictures show that the patient had complete paralysis at his right face. The right pictures show that his facial nerve (FN) function improved to H-B grade II 1 year after the hypoglossal–FN ‘side’-to-side neurorrhaphy.
DISCUSSION In the present study, we used predegenerated autologous sural nerve grafts to perform the HN–FN ‘side’-to-side neurorrhaphy followed by postoperative facial exercise in 12 patients who experienced FN injury resulting from CPA surgery for acoustic tumour removal. Six other patients did not receive repair surgery and only performed facial exercise. Using a PNG is based on the finding that Schwann cells undergo proliferation and transdifferentiate into repair cells distal to the site of nerve injury following injury, thereby providing an environment supportive of axonal regeneration.10 Indeed, animal studies in the 1990s demonstrated that the use of a predegenerated graft to bridge a nerve gap improves both the rate and the quality of axonal regeneration compared to the use of a fresh graft.11 12 We did not use fresh sural nerve grafts and end-to-side neurorrhaphy as controls for clear ethical reasons, which is the main limitation of this study, because some studies showed no difference between fresh or PNG18 and others showed an evidently increased regeneration at early time points but without difference at longer survival times.19 However, the reparative outcomes after our new facial nerve repair method were remarkable: functional improvements were detected as soon as 3 months after the repair, H-B grade II and III for FN function
were achieved in five and four patients, respectively, and there were no signs of synkinesis, a major complication associated with current methods of FN repair. The three patients who experienced less satisfactory outcomes had suffered from facial palsy for more than 1 year, consistent with a need for rapid surgical intervention. For the current methods of facial reanimation using the HN–FN end-to-end or ‘side’-to-end neurorrhaphy with or without a fresh nerve graft, the best possible outcome in a small proportion of patients is H-B grade III, and improvements are detected only after 6–12 months.4 20–24 Thus, our new surgical method, based on fundamental concepts and our own recent experimental results, represents a major advance in the rehabilitation of FN injury. After the HN–FN ‘side’-to-side neurorrhaphy in the 12 operated patients followed by facial exercise, their FN function progressively improved with the recovery of facial muscle motion involving either spontaneous reinnervation or hypoglossal innervation. On the basis of the results obtained, we found that hypoglossal motoneurons effectively regenerated towards the paralysed facial muscles via ‘side’-to-side neurorrhaphy, whether repair surgery was performed less than 6 months or more than 1 year after the onset of facial palsy, which is also consistent with the study that side-to-side nerve grafts sustain chronically
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Neurosurgery Figure 3 Facial symmetry was assessed by clinical observation of the patients. These pictures were taken from case 5 before (left) and 2 years after (right) repair surgery. The left pictures show that the patient had complete paralysis at her right face. The right pictures show that her facial nerve (FN) function improved to H-B grade IV 2 years after the hypoglossal– FN ‘side’-to-side neurorrhaphy.
Figure 4 The F wave was recorded in case 5 when electrostimulating her facial nerve at the mandibular angle. Compared with the normal F wave recorded from her intact orbicularis oris at the left side, none was recorded in the right paralysed orbicularis oris before repair surgery. Slight signals were recorded in the right orbicularis oris 3 months after repair surgery and they then improved with time. The recorded F wave still displayed delayed latency and lower amplitude 2 years after repair surgery. 6
Zhang L, et al. J Neurol Neurosurg Psychiatry 2014;0:1–8. doi:10.1136/jnnp-2014-308465
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Neurosurgery Figure 5 Muscle action potentials were detected in the orbicularis oris and orbicularis oculi when the patients voluntarily contracted their facial muscles or strongly contracted their tongue muscles to lift their tongue against their palate. This picture shows the muscle action potentials recorded in the orbicularis oculi (A) and orbicularis oris (B) of case 5 before repair surgery and 1 year after repair surgery.
denervated peripheral nerve pathways and improve functional reinnervation.25 However, for the three patients experiencing facial palsy for more than 1 year, the major challenge was irreversible atrophy of the paralysed facial muscles, causing facial disfigurement and restricted functional recovery. For the six control patients, the extent of FN recovery reached H-B grade III in one patient, grade IV in one patient and grade V in four patients at the end of the follow-up period, indicating that spontaneous reinnervation is in fact very limited, and that surgical intervention is necessary for FN recovery. For patients whose FN is anatomically preserved during CPA surgery, the remaining facial axons may spontaneously regenerate regardless of the extent of facial palsy immediately after surgery. Clearly, the classical method of HN–FN neurorrhaphy, which sacrifices the spared FN axons, is not suitable for these patients. We show here that the HN–FN ‘side’-to-side neurorrhaphy can effectively preserve FN fibres. Moreover, this ‘side’-to-side neurorrhaphy promoted double innervation of the paralysed facial muscles by hypoglossal and facial motoneurons. This is consistent with a previous study reporting that reliable restoration of resting facial symmetry and tone, powerful movements due to the innervation of hypoglossal motoneurons and a more closely physiological recovery by FN reinnervation are possible in patients with this double innervation of the paralysed facial muscles.26 In addition, the incidence of synkinesis can be reduced after facial rehabilitation surgery if the facial muscles are innervated not only by the transposed hypoglossal axons, but also by the remnant FN axons, because the shared
innervation of the facial and hypoglossal nuclei within the brainstem may prevent synkinesis of the doubly innervated facial muscles.20 27–29 On the other hand, innervation by hypoglossal motoneurons is ectopic to the facial muscles. The intense facial exercise is likely to promote central plasticity, facilitating the development of new functions for these hypoglossal motoneurons and therefore further improving functional outcomes. It is also important to preserve any remaining potential of the compromised facial mimetic muscles for recovering symmetric function in facially paralysed patients. Owing to the challenge muscle atrophy presents for functional recovery, we stress that early FN repair is necessary. In this study, we reveal that the best results were attained in those patients who had experienced facial paralysis for less than 6 months without any apparent facial muscle atrophy. To avoid muscle atrophy, some helpful facial exercise is feasible after the onset of facial paralysis, such as muscle massage and passive motion. We confirm that intense facial exercise not only delays muscle atrophy, but also improves reinnervation of the paralysed muscles.30–32 Reestablishment of functional connections between motor and sensory nervous systems is also crucial for functional recovery after nerve repair. In this study, the blink reflex did not recover, except for case 4, for whom it was recorded after 9 months. However, it is worth mentioning that the blink reflex may return after facial exercise that may facilitate the establishment of neuronal connections with the sensory afferents originating from the trigeminal nerve.33–35
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Neurosurgery In conclusion, this study demonstrates that the HN–FN ‘side’-to-side neurorrhaphy using a PNG can treat facial palsy if the injured FN is anatomically preserved. Double innervation of the paralysed facial muscles can lead to rapid functional benefits without compromising the remaining FN axons. Since ‘side’-to-side neurorrhaphy does not interrupt the main structure of the FN, it can be performed early after the onset of facial palsy when target muscles are preserved and may also be useful for the treatment of other FN injuries in which the nerve trunk is anatomically preserved, such as Bell’s palsy, after necessary conservation treatment. Contributors Conception and design: SL; Acquisition of data: LZ, DL, HW, SH, SW, DS, PL, MW, SL; Analysis and interpretation of data: LZ, DL, HW, ZW, JZ, HQ, MS, SL; Drafting the article: SL; critically revising the article: MS, SL; Reviewed submitted version of manuscript: all authors; approved the final version of the manuscript on behalf of all authors: MS, SL; Administrative/technical/material support: LZ, DL, HW, SH, SW, DS, ZW, JZ, HQ, PL, MW, MS, SL; Study supervision: LZ, HW, SL. Funding This work was supported by grants from Beijing Tiantan Hospital and Beijing Neurosurgical Institute (Beijing, China), and the Institut pour la Recherche sur la Moelle épinière et l’Encéphale (IRME, Paris, France).
12
13 14 15
16 17
18 19
20
21
Competing interests None. Patient consent Obtained.
22
Ethics approval This study was approved by the local Ethics Committee at Beijing Tiantan Hospital, Capital Medical University, China ( JS2013-001-02).
23
Provenance and peer review Not commissioned; externally peer reviewed.
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Walker DT, Hallam MJ, Ni Mhurchadha S, et al. The psychosocial impact of facial palsy: our experience in one hundred and twenty six patients. Clin Otolaryngol 2012;37:474–7. Ozsoy U, Hizay A, Demirel BM, et al. The hypoglossal-facial nerve repair as a method to improve recovery of motor function after facial nerve injury. Ann Anat 2011;193:304–13. Finsterer J. Management of peripheral facial nerve palsy. Eur Arch Otorhinolaryngol 2008;265:743–52. Wang Z, Zhang Z, Huang Q, et al. Long-term facial nerve function following facial reanimation after translabyrinthine vestibular schwannoma surgery: a comparison between sural grafting and VII-XII anastomosis. Exp Ther Med 2013;6:101–4. Matsunaga T, Kanzaki J, O-Uchi T, et al. Functional and histological evaluation of the facial nerve in patients who have undergone hypoglossal-facial nerve anastomosis after removal of cerebellopontine angle tumors. ORL J Otorhinolaryngol Relat Spec 1995;57:153–60. Fu SY, Gordon T. Contributing factors to poor functional recovery after delayed nerve repair: prolonged denervation. J Neurosci 1995;15:3886–95. Khuong HT, Midha R. Advances in nerve repair. Curr Neurol Neurosci Rep 2013;13:322. Wan H, Zhang LW, Li DZ, et al. Hypoglossal-facial nerve “side”-to-side neurorrhaphy for persistent incomplete facial palsy. J Neurosurg 2014; 120:263–72. Wan H, Zhang LW, Blanchard S, et al. Combination of hypoglossal-facial surgical reconstruction and neurotrophin 3 gene therapy for facial palsy. J Neurosurg 2013;119:739–50. Arthur-Farraj PJ, Latouche M, Wilton DK, et al. c-Jun reprograms Schwann cells of injured nerves to generate a repair cell essential for regeneration. Neuron 2012;75:633–47. Danielsen N, Kerns JM, Holmquist B, et al. Pre-degenerated nerve grafts enhance regeneration by shortening the initial delay period. Brain Res 1994;666:250–4.
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Kerns JM, Danielsen N, Holmquist B, et al. The influence of predegeneration on regeneration through peripheral nerve grafts in the rat. Exp Neurol 1993;122:28–36. Muir D. The potentiation of peripheral nerve sheaths in regeneration and repair. Exp Neurol 2010;223:102–11. House JW, Brackmann DE. Facial nerve grading system. Otolaryngol Head Neck Surg 1985;93:146–7. Martins RS, Socolovsky M, Siqueira MG, et al. Hemihypoglossal-facial neurorrhaphy after mastoid dissection of the facial nerve: results in 24 patients and comparison with the classic technique. Neurosurgery 2008;63:310–16. Kamen G. Reliability of motor-evoked potentials during resting and active contraction conditions. Med Sci Sports Exerc 2004;36:1574–9. Wedekind C, Klug N. Facial F wave recording: a novel and effective technique for extra- and intraoperative diagnosis of facial nerve function in acoustic tumor disease. Otolaryngol Head Neck Surg 2003;129:114–20. Ellis JC, McCaffrey TV. Nerve grafting. Functional results after primary vs delayed repair. Arch Otolaryngol 1985;111:781–5. Lewin-Kowalik J, Sieron AL, Krause M, et al. Predegenerated peripheral nerve grafts facilitate neurite outgrowth from the hippocampus. Brain Res Bull 1990;25:669–73. Darrouzet V, Guerin J, Bébéar JP. New technique of side-to-end hypoglossal-facial nerve attachment with translocation of the infratemporal facial nerve. J Neurosurg 1999;90:27–34. Malik TH, Kelly G, Ahmed A, et al. A comparison of surgical techniques used in dynamic reanimation of the paralyzed face. Otol Neurotol 2005;26:284–91. Flores LP. Surgical results of the hypoglossal-facial nerve jump graft technique. Acta Neurochir (Wien) 2007;149:1205–10. Mehta RP. Surgical treatment of facial paralysis. Clin Exp Otorhinolaryngol 2009;2:1–5. Rabie AN, Ibrahim AM, Kim PS, et al. Dynamic rehabilitation of facial nerve injury: a review of the literature. J Reconstr Microsurg 2013;29:283–96. Ladak A, Schembri P, Olson J, et al. Side-to-side nerve grafts sustain chronically denervated peripheral nerve pathways during axon regeneration and result in improved functional reinnervation. Neurosurgery 2011;68:1654–65. Yamamoto Y, Sekido M, Furukawa H, et al. Surgical rehabilitation of reversible facial palsy: facial-hypoglossal network system based on neural signal augmentation/neural supercharge concept. J Plast Reconstr Aesthet Surg 2007;60:223–31. Furukawa H, Saito A, Mol W, et al. Double innervation occurs in the facial mimetic muscles after facial-hypoglossal end-to-side neural repair: rat model for neural supercharge concept. J Plast Reconstr Aesthet Surg 2008; 61:257–64. Asaoka K, Sawamura Y, Nagashima M, et al. Surgical anatomy for direct hypoglossal-facial nerve side-to-end “anastomosis’. J Neurosurg 1999;91:268–75. Asaoka K, Sawamura Y. Hypoglossal-facial nerve side-to-end anastomosis. J Neurosurg 1999;91:163–4. Lindsay RW, Robinson M, Hadlock TA. Comprehensive facial rehabilitation improves function in people with facial paralysis: a 5-year experience at the Massachusetts Eye and Ear Infirmary. Phys Ther 2010;90:391–7. Wilson CM, Ronan SL. Rehabilitation postfacial reanimation surgery after removal of acoustic neuroma: a case study. J Neurol Phys Ther 2010;34:41–9. Barbara M, Monini S, Buffoni A, et al. Early rehabilitation of facial nerve deficit after acoustic neuroma surgery. Acta Otolaryngol 2003;123:932–5. Hammerschlag PE. Facial reanimation with jump interpositional graft hypoglossal facial anastomosis and hypoglossal facial anastomosis: evolution in management of facial paralysis. Laryngoscope 1999;109(2 Pt 2 Suppl 90):1–23. Bernat I, Vitte E, Lamas G, et al. Related timing for peripheral and central plasticity in hypoglossal-facial nerve anastomosis. Muscle Nerve 2006;33:334–41. Tankéré F, Maisonobe T, Naccache L, et al. Further evidence for a central reorganisation of synaptic connectivity in patients with hypoglossal-facial anastomosis in man. Brain Res 2000;864:87–94.
Zhang L, et al. J Neurol Neurosurg Psychiatry 2014;0:1–8. doi:10.1136/jnnp-2014-308465
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Hypoglossal−facial nerve 'side'-to-side neurorrhaphy using a predegenerated nerve autograft for facial palsy after removal of acoustic tumours at the cerebellopontine angle Liwei Zhang, Dezhi Li, Hong Wan, Shuyu Hao, Shiwei Wang, Zhen Wu, Junting Zhang, Hui Qiao, Ping Li, Mingran Wang, Diya Su, Michael Schumacher and Song Liu J Neurol Neurosurg Psychiatry published online September 16, 2014
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JNNP Online First, published on September 16, 2014 as 10.1136/jnnp-2014-308465 Neurosurgery
RESEARCH PAPER
Hypoglossal–facial nerve ‘side’-to-side neurorrhaphy using a predegenerated nerve autograft for facial palsy after removal of acoustic tumours at the cerebellopontine angle Liwei Zhang,1 Dezhi Li,1 Hong Wan,2 Shuyu Hao,1 Shiwei Wang,2 Zhen Wu,1 Junting Zhang,1 Hui Qiao,2 Ping Li,2 Mingran Wang,2 Diya Su,2 Michael Schumacher,3 Song Liu1,2,3 ▸ Additional material is published online only. To view please visit the journal online (http://dx.doi.org/10.1136/ jnnp-2014-308465). 1
Department of Neurosurgery and China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China 2 Beijing Neurosurgical Institute and Beijing Key Laboratory of Central Nervous System Injury, Capital Medical University, Beijing, China 3 UMR 788, INSERM and Université Paris-Sud, Le Kremlin-Bicêtre, France Correspondence to Dr Song Liu, UMR 788, INSERM et Université ParisSud, 80 rue du Général Leclerc, Le Kremlin-Bicêtre Cedex 94276, France; [email protected] LZ, DL and HW contributed equally to this study. Received 7 May 2014 Revised 7 August 2014 Accepted 28 August 2014
ABSTRACT Trial design Hypoglossal–facial nerve (HN–FN) neurorrhaphy is a method commonly used to treat facial palsy when the proximal stump of the injured FN is unavailable. Since the classic HN–FN neurorrhaphy method that needs to section the injured FN is not suitable for incomplete facial palsy, we investigated a modified method that consists of HN–FN ‘side’-to-side neurorrhaphy, retaining the remaining or spontaneously regenerated FN axons while preserving hemihypoglossal function. Methods To improve axonal regeneration, we used for the first time a predegenerated sural autograft for performing HN–FN ‘side’-to-side neurorrhaphy followed by postoperative facial exercise. We treated 12 patients who had experienced FN injury for 1–18 months as a result of acoustic tumour removal. All patients experienced facial grade V–VI paralysis according to the House-Brackmann scale, but their FN was anatomically preserved. No spontaneous facial reinnervation was detected before repair. Results Although we did not perform fresh nerve grafts and HN–FN ‘side’-to-end neurorrhaphy as controls for ethical reasons, the reparative outcomes after nerve reconstruction were remarkable: functional improvements were detected as soon as 3 months after repair, HouseBrackmann grade II or III FN functions were achieved in five and four patients, respectively, and there were no apparent signs of synkinesis. The three patients who experienced less satisfactory outcomes had exhibited facial palsy for more than 1 year accompanied by muscle atrophy, consistent with a need for rapid surgical intervention. Conclusions Based on fundamental concepts and our experimental results, this new surgical method represents a major advance in the rehabilitation of FN injury. Trial registration number JS2013-001-02.
INTRODUCTION To cite: Zhang L, Li D, Wan H, et al. J Neurol Neurosurg Psychiatry Published Online First: [please include Day Month Year] doi:10.1136/jnnp2014-308465
Facial palsy due to facial nerve (FN) injury results in facial disfigurement and the inability to express emotions with severe psychological impact for patients.1 FN injury is commonplace in accidents or cerebellopontine angle (CPA) surgery.2 In addition, FN dysfunction can result from diseases, and
approximately 20% of Bell’s palsy patients experience permanent damage.3 Surgical transposition of the hypoglossal nerve (HN) is the most commonly used procedure for innervating the FN distal stump.2 Since classic HN–FN end-to-end neurorrhaphy causes serious neurological deficits resulting from the sacrifice of the HN, surgical interventions have been improved by transferring half of the HN to the injured FN, either directly or via a nerve graft.4 However, clinical outcomes remain unsatisfactory and the postoperative recovery period is very long, sometimes beyond 2 years. Thus, regenerative therapies represent an important challenge. Two major obstacles most likely contribute to the poor reparative outcomes: a long waiting period before repair surgery, resulting in unfavourable changes in the injured FN and atrophy of its target muscles,5 and a cellular environment poorly supportive of nerve regeneration.2 6 7 Waiting for spontaneous recovery before repair surgery is indeed associated with a reduced benefit of treatment outcome. On the other hand, as the conventional HN–FN neurorrhaphy methods require sectioning of the injured FN, performing early surgery prevents spontaneous reinnervation of the spared FN axons, which is not particularly suitable for the case whose injured FN is anatomically preserved undergoing persistent incomplete facial paralysis or potential spontaneous reinnervation. In a rat model of persistent incomplete facial paralysis, we have recently demonstrated that rapid reinnervation of the whisker pad can be achieved by the HN–FN ‘side’-to-side neurorrhaphy using an interpositional nerve autograft with preservation of the injured FN.8 Thus, this method may be rapidly performed on patients without compromising the spontaneous reinnervation by the remaining FN axons. Most importantly, we used predegenerated nerve grafts (PNG) in our experiments to provide a supportive environment for axonal regeneration. The nerve graft was prepared by sectioning the peroneal nerve and using its distal segment 1 week later.8 9 This procedure is based on the concept that Schwann cells transdifferentiate into repair cells distal to the nerve injury site, thus providing a permissive environment for axon
L, etemployer) al. J Neurol Neurosurg 2014;0:1–8. doi:10.1136/jnnp-2014-308465 Copyright Article author (orZhang their 2014.Psychiatry Produced by BMJ Publishing Group Ltd under licence.
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Neurosurgery regrowth.10–12 However, the use of in vivo PNG has so far been considered as unfeasible in clinical practice.13 We report 12 patients with FN injury treated with the HN– FN ‘side’-to-side neurorrhaphy using a PNG. Six other patients who did not receive the neurorrhaphy served as controls. Their FNs were injured during the CPA surgery for removing acoustic tumours, but were anatomically preserved. All the patients experienced grade V–VI facial paralysis on the House-Brackmann (H-B) scale without any clinically apparent spontaneous reinnervation for a period of 1–18 months postinjury.14
SUBJECTS AND METHODS Between December 2010 and May 2012 in our neurosurgical centre at Beijing Tiantan Hospital, 12 patients (8 men, 4 women) who experienced unilateral facial paralysis due to acoustic tumour resection in the CPA underwent the HN–FN ‘side’-to-side neurorrhaphy using a PNG followed by a postoperative facial exercise. Six other patients (1 man, 5 women) did not receive the repair surgery but facial exercise at home, serving as controls. The age of the patients ranged from 22 to 65 years (mean 39 years). The time from the onset of paralysis to repair treatment ranged from 1 to 24 months (mean 7.3 months). All patients exhibited H-B grade V–VI facial paralysis without any clinical evidence of functional improvement before the repair treatment. Table 1 shows the H-B scale,14 and table 2 presents the general clinical data of the 18 patients. For the repair treatment with the HN–FN ‘side’-to-side neurorrhaphy and/or facial exercise, patients were informed about various aspects of their treatment, including its advantages and trade-offs.
Predegeneration of the sural nerve Predegeneration was performed by injuring the sural nerve 1 week prior to the repair surgery. Briefly, an incision of 3 cm length was performed in patients on the ipsilateral lower leg of the paralysed face side at approximately 10 cm above the midpoint of the lateral malleolus and the Achilles tendon under local anaesthesia using 2% lidocaine. After being exposed, the whole sural nerve was seriously and completely compressed one time by a pair of haemostat pliers to section the axons contained in the sural nerve, but to preserve the nerve in continuity by its epineurium, commensurate with an approximate Sunderland grade III
Table 1 House-Brackmann facial nerve grading system (House and Brackmann, 1985)
2
Grade
Description
Characteristics
I II
Normal Mild dysfunction
III
Moderate dysfunction
IV
Moderately severe dysfunction
V
Severe dysfunction
VI
Total paralysis
Normal facial function Gross: slight weakness on close inspection; may have very slight synkinesis. At rest: normal symmetry and tone Gross: obvious but not disfiguring difference between the two sides; noticeable but not severe synkinesis, contracture and/or hemifacial spasm. At rest: normal symmetry and tone Gross: obvious weakness and/or disfiguring asymmetry. At rest: normal symmetry and tone Gross: only barely perceptible motion. At rest: asymmetry No movement
injury. The damage result was verified under a surgical microscope during the surgical operation, confirming that the contained tissues were approximately sectioned with a distance of the tweezers’ tip except its epineurium. The main objective of this procedure was to create axonal degeneration in the distal segment of the sural nerve, thus stimulating the proliferation of the contained Schwann cells. In order to identify the injury site and limit axon spontaneous regeneration into the distal segment, the sural nerve was also ligated using a 6-0 nylon suture at the lesion site. The incision was then closed in layers using 4-0 nylon sutures. The patients were discharged immediately for a 1-week period. The day of repair surgery, the distal segment of the injured sural nerve was removed approximately 8 cm in length as the PNG.
Repair surgery The HN–FN ‘side’-to-side neurorrhaphy was performed identically on patients under general anaesthesia in a supine position with the head rotated towards the unaffected side. For the use of the term HN–FN ‘side’-to-side neurorrhaphy, the ‘side’ placed between quotation marks indicates that half of the HN was sectioned at the PNG bridging site and the side without quotation marks refers to laterally suturing the PNG to the injured FN without sectioning its main trunk, being different from a true end-to-side or side-to-side neurorrhaphy, because the injured hypoglossal axons can still regenerate down the original hypoglossal nerve pathway and axonal regrowth probably also occurs across a supercharged side-to-side nerve neurorrhaphy. A lazy S-shaped skin incision approximately 8 cm in length was performed from the anterior edge of the earlobe extending down the upper neck along the anterior edge of the sternocleidomastoid muscle to the level of the hyoid bone. The external jugular vein and the great auricular nerve were preserved. Figure 1 illustrates the HN–FN ‘side’-to-side neurorrhaphy procedure. Under an operating microscope, the FN was carefully exposed and dissected to free its distal portion at the two main branches in the parotid gland. The HN was exposed after posteriorly retracting the posterior belly of the digastric muscle and confirmed using a nerve stimulator. Intraoperative electrophysiological tests to record compound muscle action potentials (CMAPs) with direct nerve electrostimulation were performed for detecting the injured FN function and identifying the HN. One half of the HN was then cross-sectioned at a site closely distal to the descendens hypoglossi in order to avoid compromising sufficient glottis innervation. The proximal extremity of the PNG was surgically bridged end-to-‘side’ to the HN at the partial cross-section site via 6–8 stitches using 10-0 nylon sutures (figure 1A). An epineural window was created by using microsurgical scissors on the exposed FN at each of the two main branches. The two distal extremities of the PNG were created and then bridged to the two main FN branches end-to-side at each of the epineural windows via 3–4 stitches using 10-0 nylon sutures(figure 1B). The surgical wound was then sutured in two layers over a suction tube that was removed after 48 h. The patients were discharged 3 days after the repair surgery.
Facial exercise programme A daily facial exercise programme was initiated in the 12 surgical treatment patients 1 week after the repair surgery and in the six control patients immediately after the first consultation. The facial exercise programme included facial passive motion and massage with the aim of moving the paralysed facial muscles, such as passive eye closing, cheek drumming, brow lifting, etc, Zhang L, et al. J Neurol Neurosurg Psychiatry 2014;0:1–8. doi:10.1136/jnnp-2014-308465
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Neurosurgery Table 2 Clinical data and treatment outcome
Patient
H-B grade initial
Duration of facial paralysis (months)
Treatment
Follow-up period (months)
Case 1 Case 2 Case 3 Case 4 Case 5 Case 6 Case 7 Case 8 Case 9 Case 10 Case 11 Case 12 Contro 1 Contro 2 Contro 3 Contro 4 Contro 5 Contro 6
VI VI V VI VI VI V VI V V VI VI V VI VI V VI V
18 19 6 4 13 1 6 5 6 6 3 4 3 6 4 2 2 24
Surgery+exercise Surgery+exercise Surgery+exercise Surgery+exercise Surgery+exercise Surgery+exercise Surgery+exercise Surgery+exercise Surgery+exercise Surgery+exercise Surgery+exercise Surgery+exercise Exercise Exercise Exercise Exercise Exercise Exercise
43 39 38 35 35 35 35 32 32 30 27 25 22 20 19 20 19 16
and sometimes with the help of the patient’s fingers. We advised patients to perform the facial exercise in front of a mirror more than three times daily for at least 30 min each time. For the 12 surgical treatment patients, appropriate tongue exercise was recommended when the first signal of hypoglossal innervation in the paralysed face was detected.
Evaluation of facial reanimation and tongue movement FN function was assessed regularly using the H-B grading scale before and at 3, 6 and 9 months and beyond after the repair treatment. Each patient was also photographed and videotaped to record any changes in facial symmetry and motion. Tongue atrophy and deviation were examined according to a scale proposed by Martins et al.15
Electrophysiological examination Electromyography was performed to evaluate the electrical activity produced by the facial muscles before and after repair treatment.16 Intact muscle tissue at rest is electrically inactive, but denervated muscle produces spontaneous electrical activity that is referred to as fibrillation. In contrast, a disorderly group of action potentials with varying rates and amplitudes should appear when an innervated muscle is voluntarily contracted. Therefore, we measured the spontaneous activity of the paralysed facial muscles at rest and recorded muscle action potentials during muscle movement. Potential recordings were performed on the orbicularis oculi, orbicularis oris and tongue muscle. CMAPs were recorded in the orbicularis oculi and orbicularis oris while transcutaneously electrostimulating the FN in the mastoid area or the mandibular angle. Simultaneously, the F wave was also recorded. This is one of the late responses produced by the antidromic activation of motoneurons via supramaximal stimulation of the nerve trunk, indicating nerve conduction from the motoneuron cell body to the motor end plate.17 F wave persistence is typically 80–100% (or at least above 50%) in intact muscle.
First sign of innervation after treatment (months)
Facial function evaluation (HB grade) after treatment
3 months
6 months
9 months
Last evaluation
6 6 3 3 6 3 3 3 3 3 3 3 6 6 6 6 6 –
VI VI V V VI V V V V V V V V VI VI V VI V
V V IV IV V IV IV V V IV IV IV IV V V IV V V
V V IV III V III III IV IV IV III III III V V IV V V
V V III II IV II II III III III II II III V V IV IV V
RESULTS All patients were followed up for a mean of 29 months (ranging from 16 to 43 months) after repair treatment. For the 12 surgical treatment patients, postoperative complications were not found during the follow-up period in any of them. The initial anaesthesia of the lateral malleolus region due to ablation and predegeneration of the sural nerve appeared to be insignificant to all the patients. Tongue mobility was not impaired and neither tongue atrophy nor deviation was detected. None of the patients reported difficulty with phonation or swallowing after the neurorrhaphy surgery.
Improvement in FN function Table 2 presents the overall results of FN function for the 18 patients before and after repair treatment. For the 12 surgical treatment patients, eight and four patients, respectively, experienced H-B grade VI and V unilateral facial paralysis before repair surgery. Immediately after the HN–FN ‘side’-to-side neurorrhaphy, no further deficit in FN function was detected in any of the four patients who displayed paralysis of H-B grade V. Slight improvement in FN function was first detected in four of the eight patients who exhibited H-B grade VI facial palsy, such as barely perceptible motion of the paralysed facial muscles, as early as 3 months after repair surgery. At this time point, these four patients improved their FN function from H to B grade VI–V. Six months after the surgery, improvement of the FN function with perceptible facial motion was detected in all the 12 patients. The recovered facial muscle contraction was induced when facial voluntary motion and tongue strong contraction such as lifting the tongue against the palate. They were either slight or strong, indicating varying extents of spontaneous reinnervation by FN axons or innervation by hypoglossal motoneurons. Moreover, five cases recovered facial symmetry and tone at rest. Importantly, synkinesis was not found in the patients during eating, drinking or speaking. At the end of the follow-up period, the extent of FN functional recovery reached
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Neurosurgery of the paralysed facial muscles either during voluntary face contraction or while strongly lifting the tongue against the palate, indicating that the effective innervation of the paralysed facial muscles was established by both facial and hypoglossal motoneurons (see online supplementary video 2). We found that the patient’s recovered facial motion was much stronger when she lifted her tongue against the palate. Her FN function improved to H-B grade IV at 2 years after neurorrhaphy (figure 3). For the six control patients, slight facial voluntary contraction was found after 6 months of facial exercise. No facial contraction was detected during the follow-up period when they strongly lifted their tongue against the palate. Functional improvement of the FN was not evident with time, except for control 1 whose extent of the FN function reached H-B grade III at the end of the follow-up period. Controls 4 and 5 recovered their FN function on H-B grade IV with a return of facial symmetry and tone at rest. Facial asymmetry persisted in the remaining three patients and their FN function remained limited to H-B grade V until the end of the follow-up period (table 2).
Electrophysiological examinations
Figure 1 Schematic drawings showing surgical procedures of the hypoglossal–facial nerve (HN–FN) ‘side’-to-side neurorrhaphy. After exposing the FN and HN, the HN–FN ‘side’-to-side neurorrhaphy was performed through a predegenerated nerve graft (PNG). One end of the PNG was bridged end-to-‘side’ to the HN at the site where approximately 50% of axons were cross-sectioned (A). The other end of the PNG was bridged end-to-side to the distal FN through a window where only the epineurium was removed (B).
H-B grade II in five patients (cases 4, 6, 7, 11, 12; figure 2), grade III in four patients (cases 3, 8, 9, 10), grade IV in one patient (case 5) and grade V in two patients (Cases 1, 2; table 2). In contrast to patients with facial paralysis for less than 6 months, Cases 1, 2 and 5 with facial paralysis for more than 1 year had evident signs of muscle atrophy before repair surgery. For them, beneficial effects of repair surgery were only observed after 6 months. Case 1 did not perform intense facial exercise after the repair surgery, and his facial asymmetry persisted with FN function of H-B grade V until the end of the follow-up period. Case 2 performed intense daily facial exercise and exhibited very prominent motion of the paralysed facial muscles when he strongly lifted his tongue against the palate 1 year after the repair surgery (see online supplementary video 1). In this case, however, only slight motion of the facial muscles was detected during voluntary face contractions, suggesting that the innervation was primarily established by hypoglossal motoneurons. Since the apparent atrophy of his facial muscles did not recover, the disfigurement persisted, and his FN function was limited as H-B grade V despite the return of notable facial motion. Case 5 also performed intense facial exercise during the follow-up period, but exhibited much weaker motion of the paralysed facial muscles 6 months after the neurorrhaphy. One year after the repair surgery, however, the patient recovered detectable motion 4
Before the repair treatment, no CMAPs were detected in all 18 patients when electrostimulating the injured FN trunk at the mastoid area and the mandibular angle. Neither the F wave nor any muscle action potential was recorded at that time. We detected frequent spontaneous electrical activity (fibrillation) in the facial muscles at rest, confirming their denervation. For the 12 surgical treatment patients, CMAPs were detected in all of them when electrostimulating the FN at the mandibular angle but not at the mastoid area 3 months after the HN–FN ‘side’-to-side neurorrhaphy. Simultaneously, the F wave was also recorded, which displayed delayed latency and lower amplitude (figure 4). Muscle action potentials were detected in seven patients (cases 4, 5, 6, 8, 9, 11 and 12) in the orbicularis oris and in five patients (cases 4, 5, 6, 11 and 12) in the orbicularis oculi when they voluntarily contracted their facial muscles, indicating spontaneous reinnervation. Six months after the repair surgery, the muscle action potentials were detected in all patients except case 1, for whom muscle action potentials were detected in the orbicularis oris only after 9 months and in the orbicularis oculi after 12 months. At these time points, we also detected muscle action potentials in the orbicularis oculi and orbicularis oris muscles of the patients when they strongly lifted their tongue against the palate, confirming the innervation of the facial muscles by hypoglossal motoneurons (figure 5). The amplitude of the CMAPs, the F wave and the muscle contraction potentials increased over time in these patients, indicating progressive improvement in FN function. At the end of the follow-up period, only minor fibrillation was detected in the target muscles at rest. The blink reflex did not recover in the patients, except for case 4, for whom it was detected after 9 months postoperatively. For the six control patients, no evident CMAPs and F waves were recorded at any time of the follow-up period when electrostimulating the FN at the mandibular angle and the mastoid area, except for controls 1 and 4 when electrostimulating the FN at the mastoid area after 6 months postfacial exercise. Slight muscle action potentials were detected in the orbicularis oris and/or the orbicularis oculi of these patients when they voluntarily contracted their facial muscles, but none was recorded when their tongue was strongly lifted against the palate at the end of the follow-up period, consistent with the clinical observation.
Zhang L, et al. J Neurol Neurosurg Psychiatry 2014;0:1–8. doi:10.1136/jnnp-2014-308465
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Neurosurgery Figure 2 These pictures were taken from case 4 before repair surgery (left) and 1 year after (right) repair surgery. The left pictures show that the patient had complete paralysis at his right face. The right pictures show that his facial nerve (FN) function improved to H-B grade II 1 year after the hypoglossal–FN ‘side’-to-side neurorrhaphy.
DISCUSSION In the present study, we used predegenerated autologous sural nerve grafts to perform the HN–FN ‘side’-to-side neurorrhaphy followed by postoperative facial exercise in 12 patients who experienced FN injury resulting from CPA surgery for acoustic tumour removal. Six other patients did not receive repair surgery and only performed facial exercise. Using a PNG is based on the finding that Schwann cells undergo proliferation and transdifferentiate into repair cells distal to the site of nerve injury following injury, thereby providing an environment supportive of axonal regeneration.10 Indeed, animal studies in the 1990s demonstrated that the use of a predegenerated graft to bridge a nerve gap improves both the rate and the quality of axonal regeneration compared to the use of a fresh graft.11 12 We did not use fresh sural nerve grafts and end-to-side neurorrhaphy as controls for clear ethical reasons, which is the main limitation of this study, because some studies showed no difference between fresh or PNG18 and others showed an evidently increased regeneration at early time points but without difference at longer survival times.19 However, the reparative outcomes after our new facial nerve repair method were remarkable: functional improvements were detected as soon as 3 months after the repair, H-B grade II and III for FN function
were achieved in five and four patients, respectively, and there were no signs of synkinesis, a major complication associated with current methods of FN repair. The three patients who experienced less satisfactory outcomes had suffered from facial palsy for more than 1 year, consistent with a need for rapid surgical intervention. For the current methods of facial reanimation using the HN–FN end-to-end or ‘side’-to-end neurorrhaphy with or without a fresh nerve graft, the best possible outcome in a small proportion of patients is H-B grade III, and improvements are detected only after 6–12 months.4 20–24 Thus, our new surgical method, based on fundamental concepts and our own recent experimental results, represents a major advance in the rehabilitation of FN injury. After the HN–FN ‘side’-to-side neurorrhaphy in the 12 operated patients followed by facial exercise, their FN function progressively improved with the recovery of facial muscle motion involving either spontaneous reinnervation or hypoglossal innervation. On the basis of the results obtained, we found that hypoglossal motoneurons effectively regenerated towards the paralysed facial muscles via ‘side’-to-side neurorrhaphy, whether repair surgery was performed less than 6 months or more than 1 year after the onset of facial palsy, which is also consistent with the study that side-to-side nerve grafts sustain chronically
Zhang L, et al. J Neurol Neurosurg Psychiatry 2014;0:1–8. doi:10.1136/jnnp-2014-308465
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Neurosurgery Figure 3 Facial symmetry was assessed by clinical observation of the patients. These pictures were taken from case 5 before (left) and 2 years after (right) repair surgery. The left pictures show that the patient had complete paralysis at her right face. The right pictures show that her facial nerve (FN) function improved to H-B grade IV 2 years after the hypoglossal– FN ‘side’-to-side neurorrhaphy.
Figure 4 The F wave was recorded in case 5 when electrostimulating her facial nerve at the mandibular angle. Compared with the normal F wave recorded from her intact orbicularis oris at the left side, none was recorded in the right paralysed orbicularis oris before repair surgery. Slight signals were recorded in the right orbicularis oris 3 months after repair surgery and they then improved with time. The recorded F wave still displayed delayed latency and lower amplitude 2 years after repair surgery. 6
Zhang L, et al. J Neurol Neurosurg Psychiatry 2014;0:1–8. doi:10.1136/jnnp-2014-308465
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Neurosurgery Figure 5 Muscle action potentials were detected in the orbicularis oris and orbicularis oculi when the patients voluntarily contracted their facial muscles or strongly contracted their tongue muscles to lift their tongue against their palate. This picture shows the muscle action potentials recorded in the orbicularis oculi (A) and orbicularis oris (B) of case 5 before repair surgery and 1 year after repair surgery.
denervated peripheral nerve pathways and improve functional reinnervation.25 However, for the three patients experiencing facial palsy for more than 1 year, the major challenge was irreversible atrophy of the paralysed facial muscles, causing facial disfigurement and restricted functional recovery. For the six control patients, the extent of FN recovery reached H-B grade III in one patient, grade IV in one patient and grade V in four patients at the end of the follow-up period, indicating that spontaneous reinnervation is in fact very limited, and that surgical intervention is necessary for FN recovery. For patients whose FN is anatomically preserved during CPA surgery, the remaining facial axons may spontaneously regenerate regardless of the extent of facial palsy immediately after surgery. Clearly, the classical method of HN–FN neurorrhaphy, which sacrifices the spared FN axons, is not suitable for these patients. We show here that the HN–FN ‘side’-to-side neurorrhaphy can effectively preserve FN fibres. Moreover, this ‘side’-to-side neurorrhaphy promoted double innervation of the paralysed facial muscles by hypoglossal and facial motoneurons. This is consistent with a previous study reporting that reliable restoration of resting facial symmetry and tone, powerful movements due to the innervation of hypoglossal motoneurons and a more closely physiological recovery by FN reinnervation are possible in patients with this double innervation of the paralysed facial muscles.26 In addition, the incidence of synkinesis can be reduced after facial rehabilitation surgery if the facial muscles are innervated not only by the transposed hypoglossal axons, but also by the remnant FN axons, because the shared
innervation of the facial and hypoglossal nuclei within the brainstem may prevent synkinesis of the doubly innervated facial muscles.20 27–29 On the other hand, innervation by hypoglossal motoneurons is ectopic to the facial muscles. The intense facial exercise is likely to promote central plasticity, facilitating the development of new functions for these hypoglossal motoneurons and therefore further improving functional outcomes. It is also important to preserve any remaining potential of the compromised facial mimetic muscles for recovering symmetric function in facially paralysed patients. Owing to the challenge muscle atrophy presents for functional recovery, we stress that early FN repair is necessary. In this study, we reveal that the best results were attained in those patients who had experienced facial paralysis for less than 6 months without any apparent facial muscle atrophy. To avoid muscle atrophy, some helpful facial exercise is feasible after the onset of facial paralysis, such as muscle massage and passive motion. We confirm that intense facial exercise not only delays muscle atrophy, but also improves reinnervation of the paralysed muscles.30–32 Reestablishment of functional connections between motor and sensory nervous systems is also crucial for functional recovery after nerve repair. In this study, the blink reflex did not recover, except for case 4, for whom it was recorded after 9 months. However, it is worth mentioning that the blink reflex may return after facial exercise that may facilitate the establishment of neuronal connections with the sensory afferents originating from the trigeminal nerve.33–35
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Neurosurgery In conclusion, this study demonstrates that the HN–FN ‘side’-to-side neurorrhaphy using a PNG can treat facial palsy if the injured FN is anatomically preserved. Double innervation of the paralysed facial muscles can lead to rapid functional benefits without compromising the remaining FN axons. Since ‘side’-to-side neurorrhaphy does not interrupt the main structure of the FN, it can be performed early after the onset of facial palsy when target muscles are preserved and may also be useful for the treatment of other FN injuries in which the nerve trunk is anatomically preserved, such as Bell’s palsy, after necessary conservation treatment. Contributors Conception and design: SL; Acquisition of data: LZ, DL, HW, SH, SW, DS, PL, MW, SL; Analysis and interpretation of data: LZ, DL, HW, ZW, JZ, HQ, MS, SL; Drafting the article: SL; critically revising the article: MS, SL; Reviewed submitted version of manuscript: all authors; approved the final version of the manuscript on behalf of all authors: MS, SL; Administrative/technical/material support: LZ, DL, HW, SH, SW, DS, ZW, JZ, HQ, PL, MW, MS, SL; Study supervision: LZ, HW, SL. Funding This work was supported by grants from Beijing Tiantan Hospital and Beijing Neurosurgical Institute (Beijing, China), and the Institut pour la Recherche sur la Moelle épinière et l’Encéphale (IRME, Paris, France).
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21
Competing interests None. Patient consent Obtained.
22
Ethics approval This study was approved by the local Ethics Committee at Beijing Tiantan Hospital, Capital Medical University, China ( JS2013-001-02).
23
Provenance and peer review Not commissioned; externally peer reviewed.
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Zhang L, et al. J Neurol Neurosurg Psychiatry 2014;0:1–8. doi:10.1136/jnnp-2014-308465
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Hypoglossal−facial nerve 'side'-to-side neurorrhaphy using a predegenerated nerve autograft for facial palsy after removal of acoustic tumours at the cerebellopontine angle Liwei Zhang, Dezhi Li, Hong Wan, Shuyu Hao, Shiwei Wang, Zhen Wu, Junting Zhang, Hui Qiao, Ping Li, Mingran Wang, Diya Su, Michael Schumacher and Song Liu J Neurol Neurosurg Psychiatry published online September 16, 2014
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