Surgical and conservative methods for restoring impaired motor function - facial nerve, spinal accessory nerve, hypoglossal nerve (not including vagal nerve or swallowing).

The present review gives a survey of rehabilitative measures for disorders of the motor function of the mimetic muscles (facial nerve), and muscles innervated by the spinal accessory and hypoglossal nerves. The dysfunction can present either as paralysis or hyperkinesis (hyperkinesia). Conservative and surgical treatment options aimed at restoring normal motor function and correcting the movement disorders are described. Static reanimation techniques are not dealt with. The final section describes the use of botulinum toxin in the therapy of dysphagia.

1. Introduction

An intact function of the cranial nerves is the prerequisite for the undisturbed coordination of a large number of functions in the head and neck region. There is no question that a detailed diagnostic work-up, tailored to the individual patient, is essential prior to initiating any therapeutic measures. It is not possible to describe the individual diagnostic procedures in depth in this review. The focus will be on therapy, particularly on therapeutic modalities and procedures with only secondary emphasis on the individual disorders. We will describe how motor function can be normalized or at least improved by various conservative or surgical measures. This might entail augmenting a paucity of motor activity and movement in the case of paralysis, or reducing motor activity and movement, as e.g. in synkinesis following facial nerve trauma with aberrant regeneration. It must be mentioned that only those methods are described that restore or reduce muscle activity. Methods such as suspension techniques that are designed to improve the static function of paretic muscles are not dealt with, and the reader is referred to the appropriate literature for an in-depth description [1]. Since the subject matter as a whole is very complex, the reader is also referred to more detailed publications whenever necessary.

2. Facial nerve

2.1 General remarks

There are a wide variety of pathological conditions associated with movement disorders of the mimetic muscles. Among these are peripheral palsies of the seventh cranial nerve, such as idiopathic facial palsy, palsy in the course of varicella-zoster infection, post-traumatic palsy (extra- or intratemporal), palsy following surgery of acoustic neurinomas or malignant tumors of the parotid gland, or facial hyperkinesis, such as synkinesis due to aberrant regeneration after neural damage, facial spasm or blepharospasm [2]. The plethora of different pathologies confers a special role on the otorhinolaryngologist with the challenge of restoring mimetic muscle function to the point that emotions can be expressed in as normal a fashion as possible.

2.2 Conservative methods

2.2.1 Methods of functional rehabilitation of paralyzed mimetic facial muscles

2.2.1.1 Medical therapy

Most of the conservative treatment methods aimed at restoring mimetic function consist primarily in drug therapy. Several different therapeutic modalities have been proposed in the international literature for the treatment of idiopathic facial palsy. These range from therapeutic abstinence to invasive surgical methods [3]. The conservative approach employs a variety of medications, which are administered either singly or in combination, depending on the preference of the physician. Among these are

1. corticosteroids,

2. pentoxifylline,

3. rheologically active substances, such as dextrane or 6% hydroethyl starch (HAES), and

4. aciclovir.

Stennert recommends a 10-day regimen of Dextran 40® infusions, pentoxifylline and steroids [4] in the therapy of Bell's palsy. He reports a very high cure rate without mimetic muscle dysfunction or synkinesis in over 90% of his patients. His recommendation includes treatment of patients with facial nerve palsy due to varicella-zoster virus. A comprehensive review of this complex field would surpass the scope of this paper, since the views published in the literature on the treatment of Bell's palsy differ so widely.

A recently proposed hypothesis suggesting that reactivation of a herpes infection could be the cause of idiopathic facial palsy deserves particular attention [5], [6], [7], [8], [9], [10], since it adds weight to the recommendation that the administration of an antiviral agent should be obligatory. In our institution, we use a modified Stennert regimen with 6% HAES [11] instead of Dextran 40® for the treatment of idiopathic facial paresis, adding aciclovir as the antiviral component. Aciclovir is an established standard in the treatment of paresis caused by varicella-zoster virus. Treatment should be initiated as early as possible. The literature describes a higher incidence of aberrant regeneration with synkinesis after viral-induced than after idiopathic paresis [12].

2.2.1.2 Physiotherapy, exercise training

Physical therapeutic measures are gaining in importance in the treatment of dysfunctional mimetic facial muscles [13], [14], [15], [16], [17], [18], [19], [20], [21], [22]. Various training methods can have a beneficial influence on the functional outcome when implemented in manifest paralysis (e.g. in idiopathic palsy) or after completion of the regeneration phase (e.g. following a reconstructive procedure on the peripheral nerve).

Shimono et al. [14] demonstrated that synkinesis of the orbicularis oculi muscle was alleviated in some of their patients by biofeedback training using electromyography of the mimetic facial muscles as the controlled variable. Other authors were able to show that patients using electromyographic feedback training in the early postoperative period following hypoglossal-facial anastomosis (which always leads to aberrant regeneration) had a better rehabilitation of the mimetic facial muscles than those in a control group with no training [15], [16].

Devriese et al. [18] as well as Beurskens et al. [19] reported the improvement of synkinesis with the use of a special physiotherapeutic training program using reafferent control (mime therapy) that does not require specialized equipment. On questioning, the majority of patients with hypoglossal-facial nerve anastomosis reported that an intended (imagined) movement of the tongue was sufficient to produce various regionally specific movements of the mimetic facial muscles [20]. It thus appears that the original cortical initiation of lingual movements can be used for the new peripheral innervation of the mimetic facial muscles. It is not clear to what extent cortical connections between facial and hypoglossal nervous representation might be of relevance.

Cohen et al. [21] using transcranial magnetic stimulation found that the muscle representation areas were altered in the motor cortex of arm-amputated patients. Rödel et al. [22] have since used magnetic stimulation to confirm this finding for the facial nerve. The common characteristic of the training methods mentioned above is that the central nervous system receives "information" on the status of the mimetic muscles through e.g. electromyography or tactile stimuli.

2.2.2 Methods of functional rehabilitation of hyperkinetic mimetic facial muscles.

2.2.2.1 Botulinum toxin

Botulinum toxin has been established in the treatment of facial hyperkinesis for quite a while [for reviews see [23], [24], [25], [26], [27]]. The substance blocks the release of acetylcholine in the neuromuscular junction thus inducing a "deliberate paralysis". After being successfully employed in the treatment of patients with blepharospasm [28], [29] it has also proved very effective in the therapy of patients with facial spasms [30], [31]. Our research group was the first to use botulinum toxin in the treatment of synkinesis [32], [33]. Figure 1 (Fig. 1) shows patients with symptoms of this disorder. One can also inject a small dose of botulinum toxin (e.g. 2.5 to 2.7 units Botox®) into the levator palpebrae muscle to induce a deliberate lid ptosis to protect the cornea in patients with facial nerve palsy. One can achieve an aesthetic correction of paralysis of the marginal mandibular branch of the facial nerve [34] by the injection of botulinum toxin into the contralateral inferior depressor labii muscle (e.g. 2.5 to 5 units Botox®).

Figure 1

Patients with facial dyskinesis. Facial spasm (left), blepharospasm (center) and synkinesis following aberrant facial nerve regeneration (right).

The patient interview is of foremost importance, as it serves to establish the diagnosis and also to inform the patient of the intended treatment. At this time, the type and degree of dysfunction of the mimetic muscles is determined by questioning the patient as well as by functional testing. In our experience, patients are capable of recognizing dysfunctional regions in their face and have a strong desire that these be corrected. Tests of muscle function are very important for synkinesis [35], since attempted movements in one part of the face can initiate movement of other facial areas. These effects are objective and reproducible, and can be documented in a medical information system [36]. Palpebral fissure asymmetry measured e.g. with calipers is an example of a variable that can be used for a "before-after" comparison to assess the success of therapy. The attempted movement with the worst effect on the eye - the worst case being complete lid closure (see figure 1 for examples) - would be used in this case [32].

In addition to the points mentioned above, other phenomena can occur in definitive aberrant regeneration of the facial nerve following surgery (e.g. facial nerve reconstruction after fracture of the temporal bone or parotidectomy) that can be treated with injections of botulinum toxin. Among these are post-parotidectomy gustatory perspiration or gustatory hyperlacrimation ("crocodile tears") triggered by suitable gustatory stimuli [37], [38].

A number of injection sites have proved effective in the treatment of facial muscle dyskinesis with botulinum toxin [23], [24], [25], [26], [27] (see Figure 2 (Fig. 2)). These are determined by precise analysis of the affected muscles. The pattern of injection sites varies considerably depending on the degree and extent of the dyskinesis. The botulinum toxin (Botox® 1.25 - 2.5 units per sites) is injected subcutaneously. A number of factors must be taken into consideration when performing the injections. For example, when treating the superior portion of the orbicularis oculi muscle the injection site should not be located too far in the middle of the upper lid in order not to affect the levator palpebrae muscle. This might otherwise result in a ptosis of the affected lid. When injecting into the medial lower lid one must take care not to place the injection too far medially, since this might paralyze the muscles responsible for the active transport of tears causing lacrimation as an undesired side-effect.

Figure 2

Typical injection sites for the treatment of facial dyskinesis. The sites are determined on an individual basis, depending on the pathological movement pattern. The dose injected into each site is 1.25 and 5 units of Botox®. Caution must be exercised when injecting into the upper perioral region.

Botulinum toxin has been shown to greatly improve the patient's condition when used in the treatment of the disorders described above. This can be seen, for example, in the "calming" of the mimetic muscles (see Figure 3 (Fig. 3) for illustrations).

Figure 3

Example of botulinum toxin treatment in a patient with essential blepharospasm. The typical spasm of the orbicularis oculi muscle with recurrent attacks of complete lid closure can be seen on the left. The picture on the right emphasizes the condition after therapy with successful "opening" of the eyes.

The improvement occurs in the areas in which the substance is applied. An important aspect in the treatment of synkinesis following aberrant regeneration of the facial nerve is to adapt the palpebral fissure on the affected side to that on the healthy side during all movements of other muscles. The effect of the substance sets in about two to five days after the injection and lasts for three to four months. Subsequent injections are then required to maintain the effect.

Only few patients with "blepharospasm" do not respond to botulinum toxin injections. These could be patients with a "levator inhibitory" type, for whom frontalis suspension might be indicated. They would then be able to raise the lid by activating the frontalis muscle.

One must always keep in mind that lower doses of botulinum toxin are required in the treatment of synkinesis following aberrant regeneration of the facial nerve than for other facial indications. A further observation is that following onset an optimal effect plateau is reached which lasts for a certain time. After this period of optimal effect, the action wears off and the dysfunction will reappear in its full magnitude if the injections are not repeated. Many patients return for their follow-up injections while there is still a residual effect and the symptoms have not yet become fully manifest. This has proved to be of great benefit for the new injections.

Careful observation of the precautions described above will help minimize undesired side-effects. It is important to realize that all side-effects are only temporary and usually last for a distinctly shorter time than the desired effect of the substance. Table 1 (Tab. 1) summarizes the most important side-effects of botulinum toxin injections in the treatment of mimetic facial muscles using blepharospasm as an exemplary case.

Table 1

Side-effects in 7,692 injection series for blepharospasm (from [29])

2.3 Surgical procedures

The choice of surgical methods for reconstructing the facial nerve depends of course on the nature of the presenting lesion. The general goal is to restore the continuity of the nerve in order to provide the regenerating fibers with an effective guide. One can expect reinnervation to begin within three to four months and usually to be complete after six months.

2.3.1 Methods of functional rehabilitation of paralyzed mimetic facial muscles

2.3.1.1 Direct anastomosis of the nerves

Direct anastomosis of the central and peripheral ends of the nerve is the best surgical option when striving for effective reinnervation [39], [40], [41], [42], [43], however this is not always feasible. A clean disruption of nerve continuity e.g. after trauma or in the rare case of the nerve being severed during parotid surgery is the best precondition for an anastomosis. Epineural sutures have proved effective; perineural sutures and fibrin glue are not thought to offer any advantages [43]. Treatment should begin within one month after the lesion. Reinnervation is normally complete after six months. Synkinesis always occurs, since the axons inevitably regenerate aberrantly.

2.3.1.2 Interposition grafting

Neural interposition grafts can be used to bridge gaps in the peripheral nerve [39], [40], [41], [42], [43]. The suralis nerve is a good choice for bridging long defects. For the reconstruction of shorter defects we have seen good results using the greater auricular nerve. If the defect is due to a malignant parotid tumor we harvest the contralateral greater auricular nerve. Other nerves such as the supraclavicular, saphenus or medial nerves are only seldom used.

2.3.1.3 Hypoglossal-facial nerve graft

The hypoglossal-facial nerve graft has established itself over the years in an ever-increasing degree as an important method for restoring the function of the mimetic facial muscles [44], [45], [46], [47], [48], [49], [50], [51], [52], [53], [54], [55], [56], [57], [58], [59], [60], [61], [62]. The relevance of other methods such as the accessory-facial nerve graft has declined.

In his original publication, Körte reports on one patient with an inflammatory complication [57]. It is interesting to note that he did not perform an end-to-end anastomosis but anastomosed the hypoglossal and facial nerves side-to-end. Most authors, however, understand this method to be an end-to-end anastomosis between the distal stump of the hypoglossal nerve and the peripheral portion of the facial nerve. This method has become indispensable, but problems due to the unilateral innervation deficit of the tongue and the inevitable occurrence of synkinesis have led to modifications of the technique.

Recent publications described the excellent advantages of such modifications of the classic technique. May et al. [58] and other authors [59] have demonstrated sufficient reinnervation of the mimetic muscles and adequate movement of the tongue on the side of the "donor nerve" if only a portion of the hypoglossal axons is used in a jump graft for facial reanimation (example see Figure 4 (Fig. 4), Figure 5 (Fig. 5), Figure 6 (Fig. 6)). One can use the greater auricular nerve for this, connecting the interposition graft with an end-to-end anastomosis to the peripheral facial nerve and with an end-to-side anastomosis to the distal hypoglossal stump. In our patients we resected the cervical branch of the facial nerve during the anastomosis operation to prevent the occurrence of platysma synkinesis [60], [61]. Platysmal synkinesis is effectively prevented by this measure, since there is only little polyneural innervation of the platysma compared to the rest of the mimetic muscles, and only few sprouting axons are able to reach it during reinnervation. Recent publications are of interest in this context, which report good reinnervation of the mimetic facial muscles following anastomosis of the peripheral facial nerve stump only with the ansa hypoglossi [62]. The advantage of this method is that lingual innervation is completely retained. Further studies will show if the axons in the ansa hypoglossi are sufficient to provide satisfactory reinnervation. One problem might be that facial expression is not restored as it is with the other techniques.

Figure 4

Patient with complete facial paralysis of his left side following the removal of an acusticus neurinoma (pre-operative CAT scan in left of illustration). One can detect the total paralysis of all branches of the nerve.

Figure 5

Surgical site during a hypoglossal-facial jump graft operation. The inset in the lower right shows the great auricular interposition graft that was used. At the same time, the ramus colli of the facial nerve is severed and partially resected to prevent platysma synkinesis. One can discern the hypoglossal nerve, the facial nerve and the interposition graft (arrows).

Figure 6

Status after hypoglossal-facial jump graft operation with resection of the ramus colli of the facial nerve. One can see the good reinnervation at rest. The tongue moves normally. An interesting feature is the synkinetic eye closure when the tongue is moved, to the right as well as to the left, despite the differing innervation direction of the tongue. Synkinesis also occurs despite reduced innervation on the side of the graft (movement of the tongue to the contralateral side).

2.3.1.4 Facial nerve decompression

There is controversy over the indication for decompression of the facial nerve depending on the underlying pathology. The rationale for decompressing the nerve in its bony canal is to give the inflamed nerve room to expand, hereby interrupting the vicious circle of pressure and progressive neuronal degeneration.

Some authors decompress the nerve in patients with idiopathic facial palsy [3]. In view of the experience of Stennert [4] and of our own good results [11] we always prefer a conservative procedure for this indication.

In the case of traumatic nerve lesions, the exact indication is still in the discussion stage. In our therapeutic concept we always choose a conservative procedure if the paralysis is incomplete. Surgical decompression of the nerve should be performed if paralysis is complete and electrophysiological methods show severe axonal degeneration shortly after the injury.

We refer the reader to the detailed review of the problems by Thumfart and Stennert [63], in which the indications for surgical decompression of the nerve and method of surgical access are described for various situations.

2.3.1.5 Diversification methods

The necessity for extratemporal facial nerve reconstruction is a special situation. The standard situation is a nerve reconstruction required following its resection during curative surgery of a malignant parotid tumor. A technique known as the "diversification technique", in which mimetic function and muscle innervation is ensured from several "sources", is of interest in these cases. The goal of this diversification is the separation of the cranial from the caudal portions of the mimetic musculature in order to avoid disfiguring mass movements occurring with spontaneous emotive reactions.

Different types are defined [1], in which, for example, the upper portion of the nerve is treated with a free nerve graft (e.g. using the great auricular nerve), while the caudal portion of the mimetic musculature is reinnervated using a hypoglossofacial anastomosis. Several combinations for the extratemporal reconstruction of the facial nerve have been described [40], which usually allow the procedure to be adapted to the patient's condition. In our experience, the importance of the combination of a cross-face graft with other measures has waned. It is usually possible to obtain acceptable results using direct anastomosis or interposition grafts either alone or in combination with a hypoglossofacial anastomosis (diversification). This corresponds with the experience of other authors [64].

2.3.1.6 Cross-face graft

In this technique, axons of the ninvolved side opposite the lesion are connected to the dysfunctional side with an interposition graft, using e.g. the suralis nerve as donor nerve. Up to 50% of the fascicles of the healthy side can be incorporated. The procedure is conducted in two steps. In the first, the graft is anastomosed to the contralateral nerve and after four to six months (after the axons have sprouted) the graft is then anastomosed to the nerve of the paralyzed side. The use of the cross-face technique as the sole reanimation procedure is controversial. It is primarily viewed as a supplement to the innervation of free muscle transplants [39], [40].

2.3.1.7 Neuromuscular transposition methods

Muscle transposition refers to the insertion of an innervated ectopic muscle into the paralyzed mimetic muscles [65], [66], [67], [68], [69], [70], [71], [72]. Techniques of this type were already described in the early 20th century, and were later taken up and refined by Baker and Conley [67] and Rubin [66]. This method should be employed when a "neural" method cannot provide better results, such as in long-standing, complete paralysis. The temporal or masseter muscles are suited for use in the treatment of facial muscles (Figure 7 (Fig. 7)). The rationale behind this approach is to transpose innervated muscle portions into the region of the paralyzed muscles in order to enable movements. Depending on the individual situation and the aesthetic picture these muscle transposition procedures can be performed individually or in combination (i.e. masseter and temporalis translocation) [39], [40].

Figure 7

Principles of masseter and temporalis suspension (from [40]): The upper area (periorbital muscles) is attached to the temporalis muscle, the lower area (perioral muscles) to the masseter muscle.

A number of technical modifications have been described. In the temporalis muscle transfer, cranial muscle masses are transposed and attached in the periorbital or perioral region. Reanimation of the periorbital and perioral muscles is achieved by transposing either the temporal or masseter muscle alone, or both together, depending on the preference of the surgeon. Masseter muscle transfer can be performed via an intraoral approach to the muscle [68].

Nerve-muscle pedicle implants into the paralyzed mimetic muscles can be used to provide adequate tone to the otherwise aesthetically unsatisfactory perioral region [69], [70], [71]. Branches of the ansa cervicalis with muscle pedicles from the omohyoid, sternothyreoid and sternohydoid muscles are implanted into the paralyzed muscles. This procedure is claimed to give good results with a certain range of voluntary movements.

Free neurovascular muscle transplants have also been recommended [39], [40], [41], [42], [43]. In this procedure a muscle-nerve-vessel transplant is harvested from the gracilis muscle and inserted into the lateral perioral muscles. Perfusion and innervation of the muscle are restored by anastomosis to nearby vessels and using a cross-face transplant. Various donor muscles have been proposed, such as the gracilis, the extensor digitorum brevis, latissimus dorsi, pectoralis minor, rectus abdominis or the serratus anterior.

Favorable results in isolated paresis of the marginal branch of the mandible can be achieved by transposing the anterior belly of the digastric muscle [71]. Terzis and collaborators have studied this topic [72] and a variety of procedures for restoring dynamic muscle mechanism to the depressor labii muscle have been proposed. Among these are the transfer of the anterior digastric belly or the platysma.

2.3.2 Methods for functional rehabilitation of hyperkinetic mimetic facial muscles.

2.3.2.1 Neurectomy

Facial spasm is a typical, classical indication for the use of neurectomy. Various central and peripheral approaches are described in the literature [73], [74], [75], [76], [77], [78], [79], [80], [81], [82], [83], [84], [85], [86], [87], [88], [89], [90], [91], [92], [93], [94], [95], [96], [97], [98], [99], [100], [101], [102], [103], [104], [105], [106], [107]. Selective neurectomy is performed on individual branches of the facial nerve with the aim of permanently reducing the innervation of selected sections of the mimetic muscles. The procedure is not technically demanding and yield good results, at least temporarily [73], [74], [75], [76], [77], [78], [79], [80], [81], [82], [83], [84], [85], [86], [87], [[88], [89], [90], [91], [92], [93], [94], [95], [96], [97], [98], [99], [100], [101], [102], [103], [104], [105], [106], [107]. The main problem is that the more cranial segments of the mimetic muscles are extensively innervated and that axonal sprouts can reach the denervated muscles by various detours causing a recurrence of the pathological activity. This is due to the plethora of branches of the peripheral rami in this section of the mimetic muscles. It must be stressed that this does not hold true for the platysma [60], [61]. Since the platysma is almost exclusively innervated by the ramus colli of the facial nerve, neurectomy can give long-lasting reduction of innervation. However, depending on the pattern of innervation, segments of the platysma can be innervated by branches of the ramus marginalis manibulae of the facial nerve. Residual innervation of the cranial platysma can persist and reinnervation of this region can occur after neurectomy.

2.3.2.2 Reduction of muscle mass (myectomy)

In selected cases, dyskinetic muscles can be resected if conservative measures fail, however, this should be a measure of last resort and only rarely used. We have seen positive results in the few instances in which we resected platysma [61]. Jones et al. [101] have reported this option previously.

2.3.2.3 Decompression operation of Janetta

This operation is usually performed in patients with facial spasm. Gardner and Sava [80] found a vascular compression of the facial nerve in the root exit zone, a poorly myelinated area where the nerve leaves the brain, in 13 of 19 patients with this disorder. These results were confirmed by Jannetta and co-workers [102], [103], [104], [105], [106], [107], who found that the nerve was compressed by an artery in 90% of the patients with facial spasm. The most commonly involved vessel is the anterior inferior cerebral artery (AICA).

The principle of the operation is to decompress the nerve in its poorly myelinated section. The artery impinging on the nerve is lifted from the nerve and kept from further contact by inserting some sort of pad (see Figure 8 (Fig. 8) for an example). It is important that patients with facial spasm always be informed of the "causal" option. With the conservative botulinum therapy one has the choice between two effective treatment methods.

Figure 8

Intraoperative operation site during a decompression operation (Janetta) in a patient with facial spasm. On the left, the contact between the vessel and the nerve is easily visible. The right illustration shows the interposed material separating the vessel from the nerve.

(Photographs reproduced with the kind permission of Professor Markakis, former chairman of the department of neurosurgery, University of Göttingen)

2.3.2.4 Concluding remarks on the state of the art, perspectives and future prospects

The conclusion of this chapter focuses on several important and interesting aspects that are observed in the clinical occupation with the problems associated with facial nerve reconstruction.

- In the authors' opinion, a combination of several methods proved most beneficial for the patient in optimizing mimetic rehabilitation. The Göttingen regimen for rehabilitation of mimetic function following resection of acoustic neurinoma can serve as an example. If possible, a jump-anastomosis should be used for anastomosing the hypoglossal and facial nerves in order to reduce lingual movement disorders, and the ramus colli of the facial nerve should be resected to minimize platysma synkinesis. Training including reafferent control (trigeminal nerve, mime therapy, biofeedback methods) should commence in the immediate postoperative period. Treatment with botulinum toxin to reduce existing synkinesis can be employed for the final corrections after reinnervation is completed. This entire program takes eight to 12 months.

- The hypoglossal-facial anastomosis with its various modifications (see above) has proved to be an important and effective measure as well as a very interesting neurobiological model. The regeneration potential of the hypoglossal nerve is undisputed, but many of the events that take place in the central nervous system after such an operation are still unknown, although numerous study groups are researching the topic (for a review see [108]). There is still potential for further improvement.

- A crucial point that requires further work is the synkinesis resulting from aberrant regeneration or following nerve reconstruction. This mimetic stigma is a considerable problem for the patient, and can lead to psychosocial disturbances [109]. One promising perspective is that a rationally founded concept incorporating special exercise therapy and training methods can be developed. In the authors' opinion, the key to understanding the development, manifestation and successful therapy of synkinesis is not to concentrate solely on the aberrant peripheral axonal sprouting. Recent studies have shown that supranuclear (cortical) regenerative mechanisms are involved following peripheral facial nerve damage (for an introduction see [110], [111]). This opens an immense theoretical field for therapeutic innovation, which includes both preventive measures (during reinnervation) as well as the treatment of manifest pathological states (manifest aberrant facial nerve regeneration). A fascinating idea in this context is the possibility of directed axonal sprouting during regeneration, perhaps guided or enhanced by growth factors, or the possibility of controlling the number of motor end-plates developing during regeneration [112], [113], [114].

3. Spinal accessory nerve

3.1 General remarks

Paralysis is the most common motor dysfunction of the spinal accessory nerve, as a consequence e.g. of neck dissection [115]. The clinical symptoms result from the disrupted innervation of the neck and shoulder muscles. It is important to note the loss of sternocleidomastoid function. This presents as a loss of muscle contour, which is particularly visible when the head is turned to the opposite side. Loss of trapezius muscle function causes the shoulder to sag and shift laterally on the affected side. The scapula drops in a caudal-lateral direction and the medial margin stands out ("winging", see Figure 9 (Fig. 9)). Supination, abduction and elevation of the arm are impaired, but sensory function is normal. Most patients complain of shoulder pain.

Figure 9

Patient with transient postoperative paralysis of the spinal accessory nerve. The illustrations on the left show the preoperative status with adequate and symmetrical innervation of the trapezius muscle during various movements of the arm and shoulder. In the illustrations on the right taken postoperatively one can easily discern the loss of muscle contour during the same movements. The inferior portion of the trapezius muscle is particularly affected, since the upper segments of the muscle is not solely innervated by the spinal accessory nerve.

Paralysis of the spinal accessory nerve can be due to a variety of causes [116]. In addition to iatrogenic damage (e.g. neck surgery, radiation therapy or false position) it can be caused by gunshot wounds, diseases of the cervical spine or occurs as idiopathic palsy. Pathological conditions of the base of the skull such as fractures or tumors encroaching on the jugular foramen can cause symptoms of peripheral accessory nerve paralysis.

One must also mention centrally mediated movement disorders of the muscles innervated by the spinal accessory nerve, for which cervical dystonia is a typical example. Cervical dystonia is the most common form of idiopathic dystonia (Figure 10 (Fig. 10)). The mean age at first manifestation is about 40 years, and women are affected slightly more frequently than men (1.2 : 1.0). Most patients report a gradual onset and increase of the symptoms. The patients suffer from involuntary tonic, tremorous or phasic muscle activity usually involving the sternocleidomastoid, splenius capitis and trapezius muscles but also the scalenus group and the levator scapulae muscle. Impaired function (motion), pain and social stigmatization are the foremost complaints, while secondary damage to the cervical spine can appear over time.

Figure 10

Example of a patient with the typical picture of mild cervical dystonia (see upper part of illustration). The patients often interrupt the symptoms by performing specific antagonistic movements (geste antagonistique, see upper right). A marked improvement is seen after the injection of 40 units of Botox® into the right sternocleidomastoid muscle. The patient can now move her head in all directions.

The classification in anterocollis, retrocollis and laterocollis is based on the pattern and direction of motion. A typical phenomenon is that the patients can suppress the dystonic movement by tactile stimulation of the chin, the occiput or the vertex. This is known as the sensory trick or "geste antagonistique".

3.2 Conservative methods

3.2.1 Methods for functional rehabilitation of paralyzed muscles

3.2.1.1 Physiotherapy

Specific concepts of exercise therapy are employed when the musculature is paretic. Physiotherapy is one suitable measure in the treatment of paralysed musculature innervated by the spinal accessory nerve, but there is altogether only sparse mention of this complex in the literature. In a recent study, McNeely et al. [117] demonstrated the advantages of a special method (progressive resistance exercise training, PRET), but pointed out that randomized studies of this complex are completely lacking. PRET is a detailed training program containing various elements to strengthen the shoulder muscles.

A special concept was developed in our clinic [118] aimed at enabling pain-free use of the arms, restoring or improving the range of arm movements, and improving muscular function and mobility of the cervical spine that was limited by muscle guarding (Figure 11 (Fig. 11)).

Figure 11

Physiotherapy in a patient with accessory nerve paralysis

Left: Part of sequence designed to retension the muscle surrounding the scapula (important when pain is present)

Right: Stabilization of the auxiliary muscles during innervation of the weakened trapezius muscle (equipment: stave)

These goals are attained by measures such as:

- Retensioning by methods designed to regulate muscle tone, e.g. passive and active movement of the scapula

- Kneippism therapy (including ice)

- Coordination training of the muscles surrounding the scapula, particularly the rhomboid muscles, the serratus anterior and the levator scapulae muscles (auxiliary muscles)

- Preservation of the mobility of the shoulder joint and instruction of the patient on how to stretch and activate the auxillary muscles on their own

- Promote the innervation of the trapezius and sternocleidomastoid muscles

- Facilitation of physiological movements of the cervical spine and perception of the spatial orientation of the head

- Providing appropriate aids (e.g. clavicle bandage)

When these measures are implemented the prognosis of paralysis following functional neck dissection without loss of nerve continuity is favorable.

3.2.2 Methods for functional rehabilitation of hyperkinetic muscles

3.2.2.1 Botulinum toxin

Since the late 1980s, botulinum toxin has been the treatment of choice for cervical dystonia (Figure 10 (Fig. 10)) [119], [120], [121]. The direct application into the affected muscles has no systemic side-effects, contrary to those frequently seen with many of the previously used centrally acting drugs, and allows a symptom-oriented, effective therapy.

Injecting the botulinum toxin into the hyperkinetic muscles with a cannula that permits the simultaneous registration of EMG activity has become standard, since this ensures optimal placement in the targeted muscles. The amounts of substance used for this indication are markedly larger than those used for facial injections, which explains why the induction of antibody production can be observed more frequently. We often inject a total of 40 to 120 or more units of Botox®. Temporary side-effects of this treatment are dry mouth (up to 21.9%), dysphagia (up to 21.9%), local pain (up to 14%), drowsiness (to 18.4%), slurred speech (4.3%) and nausea (1.3%).

3.2.2.2 Physiotherapy, exercise training

The few available recent reports in the literature [122] describe EMG feedback methods and physiotherapy programs with passive stretching of the musculature as equivalent in their effectiveness. It should be pointed out in this context that physiotherapy is always of value as a supportive therapeutic measure.

3.3 Surgical procedures

The use of reconstructive surgery depends of course on the presenting pathology. The aim of all surgical interventions is to restore neural continuity without inducing surrounding scar tissue formation.

3.3.1 Surgical procedures for restoring the function of paralyzed muscles

Surgical intervention to restore the function of the spinal accessory nerve can be beneficial in specific conditions (for the respective indications see [123]). Among these one can list the end-to-end anastomosis when the situation allows a tension-free coaption, such as following iatrogenic transection. If this is not feasible an autologous nerve transplant or interposition graft (e.g. greater auricular or suralis nerve) can be used. If the continuity of the nerve is assumed to be preserved and only scar tissue is present one would recommend neurolysis.

3.3.2 Surgical procedures for restoring the function of hyperkinetic muscles

Various surgical methods have been described for reducing bouts of dystonic movements. Interventions for cervical dystonia are available if botulinum toxin therapy or other options are not successful. There are various approaches [124], [125], [126], [127], [128], [129]. Some of these are performed as a selective peripheral denervation, i.e. the nerves innervating the dystonic muscles are transected. This can be performed as an intradural ventral rhizotomy or as an extradural peripheral neurotomy (Bertrand's procedure). Recent literature reports satisfactory results [124], [125], [126], [127], [128]. Functional stereotactic procedures are available as an alternative. The principle lies in the elimination of "motor centers" in the central nervous system at various levels. Multiple target structures of these stereotactic methods are known [129].

4. Hypoglossal nerve

4.1 General remarks

Paralysis of the hypoglossal nerve can be due to a variety of causes. One differentiates clinically central, nuclear and peripheral forms. A unilateral paralysis of the peripheral nerves results in lingual dysglossia. The patients complain of an impairment of the apical sounds [130]. With peripheral paralysis one finds an emphasis of the non-involved side of the tongue at rest, frequently with a sulcus formation (Figure 12 (Fig. 12)). The tongue deviates to the affected side on protrusion due to the greater force acting on the healthy side. Bilateral paralysis severely interferes with articulation. Paralysis is seen associated with tumors of the central nervous system, clivus chordomas, hypoglossal neurinomas, osteolytic metastases of the skull base, malignant glossal tumors as well as with tumors of the cervical spine. Inflammatory causes are also known, such as basal meningitis or mononucleosis. Vascular malformations in the brain stem or variants of the course of the internal carotid artery ("kinking") can cause hypoglossal paralysis. Trauma such as gunshot wounds, blunt injury or iatrogenic damage (neck dissection, carotid artery surgery, for review see [116]) also plays an important role.

Figure 12

Typical picture of a unilateral hypoglossal paralysis. The deviation of the protruded tongue to the affected side is visible. This is caused by the greater innervation of the uninvolved side. A "classic" hypoglossal-facial anastomosis was performed in this patient. For a comparison with a jump graft see Figures 4 to 6

Hyperkinesis of the lingual musculature can occur in the course of oromandibular dystonia causing protrusion of the tongue. Certain drugs can interfere with lingual mobility.

4.2 Conservative therapy

4.2.1 Treatment methods for paralyzed lingual musculature

4.2.1.1 Speech therapy, exercise training

Therapy options are described for the treatment of symptomatic unilateral and bilateral peripheral hypoglossal paralysis [130], [131], [132], [133], [134]. Tongue movements are trained by voicing consonants and vowels. Visual feedback is important since there is only little kinesthetic perception with which to control the tongue. Electrical stimulation is considered suitable for peripheral paralysis [130]. These therapy options should be conducted and supervised by experienced speech therapists.

4.2.2 Treatment methods for hyperkinetic lingual musculature

4.2.2.1 Botulinum toxin

The clinical presentation of oromandibular dystonia (example see Figure 13 (Fig. 13)) is very variable. Involuntary movements of the tongue can occur as well as jaw opening, lateral deviation or jaw clenching. Oromandibular dystonia in combination with blepharospasm is known as Meige syndrome. The movement disorders in oromandibular dystonia are often very complex. Treatment with botulinum toxin is difficult, since involvement of the tongue, which causes the greatest suffering in the affected patients, is frequent, yet the injection of botulinum toxin directly into the intrinsic lingual musculature is contraindicated due to the associated symptoms of dysarthria and dysphagia. Frequently, only palliation of the symptoms is possible [133]. It is important to identify the dystonic muscles during the diagnostic work-up by inspection, palpation and, if necessary, by electromyography, and then to inject them selectively. It is always possible to inject directly into the temporalis, masseter, medial and lateral pterygoid, anterior digastric, genioglossus and hypoglossus muscles. Compared with all other indications, side-effects are relatively common during the treatment of oromandibular dystonia (5 - 7%). Dysphagia can be caused by injecting into the "wrong" muscles, relative overdose or by unanticipated diffusion of the toxin.

Figure 13

Patient with oromandibular dystonia and typical protrusion of the tongue. These patients can also have dysarthria and/or dysphagia in addition to the aesthetic aberration. Secondary changes such as temporomandibular joint arthrosis can occur in long-standing disease.

An interesting effect is a remote effect on muscles that were neither treated nor are adjacent to treated muscles. Injections given exclusively periorbitally for the treatment of patients with Meige syndrome can effect a temporary reduction in the pathological movements of oromandibular dystonia. The reason for this remote effect is unclear. A feedback mechanism mediated through trigeminal neurons has been proposed by which information on the altered state of the treated muscles can influence the central nervous system. Doses of 30 to 120 units of Botox® are used.

4.3 Surgical procedures

The use of surgical procedures for the treatment of lingual paralysis is hardly mentioned in the literature. The main difficulty is that differentiated control over tongue movements cannot be attained by anastomosis of the nerve after disruption of its continuity due to uncontrolled reinnervation. Since functional deficits are limited even in the case of permanent paralysis the expected results would not warrant the surgical efforts. If the etiology of the paralysis is obvious, as e.g. in the case of an acute iatrogenic transection of the nerve, the authors hold that it should be anastomosed in the course of tending to the wound. The aim is to maintain the muscle tone of the tongue, since at that point it is not possible to predict the extent of paralysis. An important aid in the decision on surgical intervention in cases of long-standing paralysis should be the answer to the question of just how relevant the paralysis is to the affected patient and what one could hope to achieve with an operation. It is important to mention the problems associated with using the XIIth cranial nerve for facial nerve repair (hypoglossal-facial graft). The most current technique aims at preserving as many hypoglossal axons as possible during the procedure. This is assured using the jump graft described by May et al. [58] in which an end-to-side anastomosis is performed (see above and also [59]). This also preserves the exact topographical representation of the functioning axons in the cortex. Other authors use the ansa nervi hypoglossi to innervate the tongue in patients with a hypoglossal-facial graft [62]. In the authors' opinion one should attempt to reinnervate the tongue (ansa cervicalis) or to preserve innervation as far as possible during hypoglossal-facial graft surgery, since the patients can experience problems with facial function [134]. Simple improvement of muscle tone alone can decrease the problems. In a follow-up study of patients with a "classic" hypoglossal-facial graft in our institution 26% of the patients complained of dysphagia, 19% had impaired oral continence, 11% had dysarthria and 7% had problems with lingual motility.

The approach described by Rubin et al. [135], [136] should be mentioned in this context. They propose the use of a Z-plasty in patients with unilateral peripheral lingual paralysis. In this procedure, normally innervated lingual muscles are transposed into the paralyzed musculature and are thought to improve muscle tone.

5. Botulinum toxin in the therapy of dysphagia

Botulinum toxin is effective in ameliorating the pharyngeal and esophageal muscle dysfunction in selected types of dysphagia [137], [138], [139], [140]. The cricopharyngeal muscle acts as a superior esophagus sphincter and impaired relaxation of this muscle during the swallowing act can cause dysphagia. This spasm is a common symptom of numerous neurological diseases, e.g. following stroke (example see Figure 14 (Fig. 14)), in post-polio syndrome or amyotrophic lateral sclerosis. Idiopathic occurrence is also described.

Figure 14

Case study of a patient who suffered ischemia of the dorso-lateral medulla oblongata. He suffered from severe dysphagia with recurrent aspiration, and a tracheotomy was necessary. The esophageal introitus was completely closed by the musculature. This can be seen on the left - a pool of contrast medium spills into the larynx and trachea down to the inflated cuff of the cannula. No appreciable improvement was seen after treatment with baclofen (centrally acting muscle relaxant). This was supplemented by the circular injection of 75 units of Botox® in the muscles of the esophageal introitus. In addition, a total dose of 70 units of Botox® was injected bilaterally into the submandibular and parotid glands (22.5 units into each parotid, 12.5 into each submandibular gland). The control examination three weeks after the injections revealed a completely unimpaired passage of the contrast medium (right side of illustration). The PEG tube was removed, and the patient was discharged to a rehabilitation facility without dysphagia or aspiration.

Botulinum toxin injections can obviate the need for surgery (e.g. dilation, plexus neurectomy, cricopharyngeal myotomy) in many patients, many of whom are elderly and have significant co-morbidity.

Botulinum toxin injections can also be used in the treatment of dysphagia due to scarring with absent or diminished relaxation of the esophageal introitus following tumor surgery. Following laryngectomy with cictricial stricture or spasm of the esophageal-pharyngeal junction, botulinum toxin can not only improve swallowing but also the tracheo-esophageal voice. An interdisciplinary evaluation of the dysphagia and an exact functional diagnostic work-up (e.g. with video fluoroscopy or esophagus manometry) is required before beginning treatment.

Botulinum toxin is usually injected transorally under a short general anesthetic, e.g. a total dose of 30 to 60 units of Botox®, spread over three sites in the dorsal pharynx (right and left lateral, medial dorsal, see Figure 15 (Fig. 15)). Used as a transoral supplemental treatment following laser cricopharyngeal myotomy, botulinum toxin provides better long-term results, since less scar tissue strictures with stenosis occurs during healing because the fibers in the relaxed muscles are farther apart [140].

Figure 15

Microlaryngoscopic picture of the esophageal introitus prior to botulinum toxin injection. A total dose of 75 units of Botox® was injected. The dots illustrate the injection sites.

Acknowledgement

We want to thank B. Fechner for his help (see Figure 11 (Fig. 11)). The described treatment option has been developed by him and is in clinical use since 1987.