Synkinesis

Synkinesis is the result from miswiring of nerves after trauma. This result is manifested through involuntary muscular movements accompanying voluntary movements. For example, voluntary smiling will induce an involuntary contraction of the eye muscles causing the eye to squint while you smile.

Causes

Almost all cases of synkinesis develop as a sequel to nerve trauma (the exception is when it is congenitally acquired as in Duane-Retraction Syndrome and Marcus Gunn phenomenon). Trauma to the nerve can be induced in cases such as surgical procedures, nerve inflammation, neuroma [cite journal |author= Rubin DI, Matsumoto JY, Suarez GA, Auger RG.|title=Facial trigeminal synkinesis associated with a trigeminal schwannoma. |journal=Neurology |volume=53 |issue=3 |pages=635–7 |year=1999 |pmid=10449135] , and physical injurycite journal |author=Buckley EG, Ellis FD, Postel E, Saunders T |title=Postraumatic Abducens to Oculomotor Nerve Misdirection |journal=Journal of AAPOS |volume=9 |issue=1 |pages=12–16 |year=2005 |pmid=15729274] .

Variations

Since synkinesis is ultimately an interaction of nerves with muscles(although glands can also be involved), almost all studied cases are relevant to the cranial nerves where they interact with many small cranial muscles, most of which are responsible for separate and unique functions. This is in contrast to areas of our body where miswiring of the larger muscles is less common due the size of the muscles. The two cases of synkinesis most commonly studied involve the facial muscles and the extraocular muscles.

Facial Synkinesis

Facial Synkinesis is a common sequelae to Idiopathic Facial Nerve Paralysis, also called Bell’s Palsy or Facial Palsy [cite journal |author=Beurskens CH, Heymans PG. |title=Mime therapy improves facial symmetry in people with long-term facial nerve paresis: a randomised controlled trial. |journal=Aust J Physiother. |volume=52 |issue=3 |pages=177–83 |year=2006 |pmid=16942452] . Bell’s Palsy, which occurs due to the compression of the seventh cranial nerve, results in a hemifacial paralysis due to non-functionality of the nerve. As the nerve attempts to recover, nerve miswiring results (see Mechanism of Action below). In patients with severe facial nerve paralysis, facial synkinesis will inevitably developcite journal |author=Nakamura K, Toda N, Sakamaki K, Kashima K, Takeda N. |title=Biofeedback rehabilitation for prevention of synkinesis after facial palsy. |journal=Otolaryngol Head Neck Surg. |volume=128 |issue=4 |pages=539–43 |year=2003 |pmid=12707658 |doi=10.1016/S0194-5998(02)23254-4] . Additionally, a common treatment option for facial palsy is to use electrical stimulation. Unfortunately, this has been shown to be disruptive to normal re-innervation and can promote the development of synkinesis [cite journal |author=Manikandan N. |title=Effect of facial neuromuscular re-education on facial symmetry in patients with Bell's palsy: a randomized controlled trial. |journal=Clin Rehabil.. |volume=21 |issue=4 |pages=338–43 |year=2007 |pmid=17613574 |doi=10.1177/0269215507070790] . The most common symptoms of facial synkinesis include [cite journal |author=Mehta RP, WernickRobinson M, Hadlock TA. |title=Validation of the Synkinesis Assessment Questionnaire. |journal=Laryngoscope. |volume=117 |issue=5 |pages=923–6 |year=2007 |pmid=17473697 |doi=10.1097/MLG.0b013e3180412460] :
*Eye closure with volitional contraction of mouth muscles
*Midfacial movements with volitional eye closure
*Neck tightness (Platysmal contraction) with volitional smiling
*Hyperlacrimation(also called Crocodile Tears)
**A case where eating provokes excessive lacrimation. This has been attributed to neural interaction between the salivary glands and the lacrimal glands cite journal |author= Montoya FJ, Riddell CE, Caesar R, Hague S. |title= Treatment of gustatory hyperlacrimation (crocodile tears) with injection of botulinum toxin into the lacrimal gland. |journal=Eye. |volume=16 |issue=6 |pages=705–09 |year=2002 |pmid= 12439663 |doi= 10.1038/sj.eye.6700230 ] .

Extra-Ocular Muscle Synkinesis

The six muscles around the eye (extraocular muscles) are innervated by three different cranial nerves: Abducens (6th nerve), Trochlear (4th nerve), and Oculomotor (3rd nerve). After nerve trauma around the eye, a combination of any two of these three cranial nerves have been shown to be involved with extra-ocular synkinesis. More over, while the abducens and the trochlear nerve each innervate one specific muscle, the oculomotor nerve has many functions including eye-lid retraction and pupil constriction. Thus, during synkinesis, a variable of these functions are involved. Examples include:
* On attempted abduction of an affected eye, the eye adducts and the eye-lid retracts.
**This is an interaction between the abducens nerve and a branch of the oculomotor nerve. Voluntary activation of the abducens nerve (eye abduction) causes involuntary activation of the oculomotor nerve (eye adduction and eye-lid elevation).
* On attempted abduction, the eye’s unreactive pupil constricts
**Another interaction, yet different, between the abducens nerve (eye abduction) and the oculomotor nerve (pupil constriction) [cite journal |author=Pfeiffer N, Simonsz HJ, Kommerell G. |title=Misdirected regeneration of abducens nerve neurons into the parasympathetic pupillary pathway. |journal=Graefes Arch Clin Exp Ophthalmol. |volume=230 |issue=2 |pages=150–3 |year=1992 |pmid=1577295 |doi=10.1007/BF00164653] .
* On attempted adduction with eye depression, the eye-lid retracts.
**This is a case reported in which voluntary activation of the trochlear nerve (eye depression + eye abduction) is involuntarily activating a branch of the oculomotor nerve responsible for eye-lid retraction [cite journal |author=Kothari M, Hussain A, Kar D, Toshniwal S. |title=Primary superior oblique muscle-levator muscle synkinesis. |journal=J AAPOS |volume=11 |issue=2 |pages=204–5 |year=2007 |pmid=17416331] .

Other less common variations of synkinesis involving the cranial nerves include:

*Trigeminal-Abducens Synkinesis
**After physical trauma to the skull, the muscle involved in eye abduction can become reinnervated by the branch of the trigeminal nerve involved in innervating the muscles of mastication(chewing muscles). Thus, involuntary abduction of an involved eye will occur upon eating or chewing [cite journal |author=McGovern ST, Crompton JL, Ingham PN. |title=Trigemino-abducens synkinesis: an unusual case of aberrant regeneration. |journal=Aust N Z J Ophthalmol. |volume=14 |issue=3 |pages=275–9 |year=1986 |pmid=3768184 |doi=10.1111/j.1442-9071.1986.tb00049.x] .
*Trigeminal-Facial Synkinesis
**After surgical trauma, the muscles of mastication can become reinnervated by the facial nerve as opposed to the trigeminal nerve. This causes weakness in voluntary chewing; also, facial movements such as blinking cause the muscles to contract [cite journal |author= Rubin DI, Matsumoto JY, Suarez GA, Auger RG.|title=Facial trigeminal synkinesis associated with a trigeminal schwannoma. |journal=Neurology |volume=53 |issue=3 |pages=635–7 |year=1999 |pmid=10449135] .

Mechanism of Action

There are three proposed mechanisms for synkinesis: aberrant nerve regeneration, interneuronal ephaptic transmission, and nuclear hyperexcitability.

Aberrant Nerve Regeneration

The aberrant nerve regeneration hypothesis is the most widely accepted mechanism for synkinesiscite journal |author= Moran CJ, Neely JG. |title=Patterns of facial nerve synkinesis. |journal=Laryngoscope |volume=106 |issue=12 |pages=1491–6 |year=1996 |pmid=8948609 |doi=10.1097/00005537-199612000-00009] . The hypothesis states that, after trauma, axons project from the facial nucleus to incorrect peripheral muscle groups. These aberrant branches can simultaneously innervate different subdivisions of the facial nerve . For example: compression to the facial nerve causes a lesion and the set of axons that innervates your orbicularis oris (mouth muscle) degenerate. Once the compression has relieved, regeneration of axons from the lesion site begins. This time though, only 50% of the set of axons that innervate your orbicularis oris successfully reinnervate the original site. The other half aberrantly branched off and innervated the orbicularis oculi(eye muscle). Thus, when you voluntarily want to purse your lips or smile, the ipsilateral eye will squint.

The hypothesis assumes that disorganized regeneration occurs at the site of the lesion. On the contrary, recent research by Choi and Raisman [cite journal |author=Choi D, Raisman G. |title=After facial nerve damage, regenerating axons become aberrant throughout the length of the nerve and not only at the site of the lesion: an experimental study. |journal=Br J Neurosurg. |volume=18 |issue=1 |pages=45–8 |year=2004 |pmid=15040714 |doi=10.1080/02688690410001660454] has provided a more thorough understanding of synkinesis through aberrant axonal regeneration. Their study has shown that regenerating axons become disorganized throughout the length of the nerve and not only at the site of the lesion. Previously, many developed treatment strategies (that inevitably failed) were invented based on the original hypothesis by only focusing on the lesion site for improving the organization of regeneration. The new modification to the hypothesis could allow for better success in developing treatments.

Ephaptic Transmission

Ephaptic transmission is when two nerves communicate with each other via an artificial synapse between nerves. Healthy peripheral nerves are insulated with a myelin sheath that helps to both enhance electric transmission and to prevent cross-talk between parallel nerves. After a lesion, it has been observed that regenerating nerves might not be myelinated effectively. Consequently, the two nerve fibers can come into contact and provide a means for an impulse to be directly conducted through the nerve membrane. An example to clarify this is having two uninsulated electrical wires placed adjacent to each other. Thus, the two nerves are able to “cross-talk” and send action potentials in both directions [cite journal |author=Sadjadpour K. |title=After Postfacial palsy phenomena: faulty nerve regeneration or ephaptic transmission? |journal=Brain Res. |volume=95 |issue=2-3 |pages=403–6 |year=1975 |pmid=168941 |doi=10.1016/0006-8993(75)90117-1] .

Nuclear Hyperexcitability

The basis of this hypothesis is as follows: after a lesion, axonal degeneration (via Wallerian degeneration) occurs. The post-synaptic cell consequently becomes deprived of input and becomes more sensitive to neurotransmitters (e.g. creating additional receptors). Subsequently, residual undamaged axons in the same premise of the lesion can provide a source of neurotransmitter to the deprived post-synaptic cell. Since the post-synaptic cell is hypersensitive, the neurotransmitters that reach it from an axon of another nerve will successfully provide stimulation. This consequently creates undesired peripheral movement (i.e. synkinesis) [cite journal |author=Sibony PA, Lessell S, Gittinger JW Jr. |title=Acquired oculomotor synkinesis. |journal=Surv Ophthalmol. |volume=28 |issue=5 |pages=382–90 |year=1984 |pmid=6372143 |doi=10.1016/0039-6257(84)90243-1] .
*Since synkinesis has been reported in patients within 1-2 months, the nuclear hyper-excitability hypothesis is being supported by more researchers . Furthermore, axonal regeneration is a slow process (~1 mm/day growth) and regeneration at this rate of the facial nerve would roughly take 4-8 months. Since synkinesis is observed much earlier, aberrant regeneration and ephaptic communication fail to explain for this observation thus providing evidence that nuclear hyper-excitability is an important factor in the mechanism of synkinesis development. [cite book |title= The Facial Nerve|last= May |first= Mark |authorlink= |coauthors= Barry M. Schaitkin |year=1999|publisher= Thieme |isbn= 0865778213|pages=49] .

Although these three mechanisms have been argued for and against in various ways, it has become more accepted that synkinesis develops through a combination of these mechanisms.

Measuring Synkinesis

Until May 2007, there was no clinical scale to measure synkinesis. A study led by Mehta et al. [cite journal |author=Mehta RP, WernickRobinson M, Hadlock TA. |title=Validation of the Synkinesis Assessment Questionnaire. |journal=Laryngoscope. |volume=117 |issue=5 |pages=923–6 |year=2007 |pmid=17473697 |doi=10.1097/MLG.0b013e3180412460] has validated the use of a newly designed instrument to evaluate facial synkinesis called the Synkinesis Assessment Questionnaire (SAQ). The instrument, consisting of nine questions, was found to be both reliable and valid. In addition, it is simple, easy to administer, and inexpensive. Its analyses can allow for treatment options to be evaluated.

Treatment

Experimental research for treatment has been mostly focused on facial synkinesis due to its abundant prevalence compared to extra-ocular synkinesis. Additionally, since the extra-ocular muscles are hidden within the orbits, there is a limit on the type of practical treatments that can be established (e.g. massage). Established treatments for synkinesis in general include surgery; furthermore, facial synkinesis has the benefit of less invasive treatments such as facial retraining, biofeedback, mime therapy, and Botox.

urgery

Practical surgical procedures used for treating synkinesis are neurolysis and selective myectomy. Neurolysis has been shown to be effective in relieving synkinesis but only temporarily and unfortunately symptoms return much worse than originally [cite book |title= The Facial Nerve|last= May |first= Mark |authorlink= |coauthors= Barry M. Schaitkin |year=1999|publisher= Thieme |isbn= 0865778213|pages=467] . Selective myectomy, in which a synkinetic muscle is selectively resected, is a much more effective technique that can provide permanent relief and results in a low recurrence rate; unfortunately, it also has many post-operative complications that can accompany including edema, hematoma, and ecchymosis . Therefore, surgical procedures are very minimally used by doctors and are stored as last-resort options for patients that do not respond well to non-invasive treatments.

Facial Retraining

Facial retraining therapy builds upon the idea that neurons are constantly in a dynamic state. In other words, there is constant growth and regression of neuronal projections dependent on the stimuli produced. To reduce synkinesis, facial retraining teaches the patient techniques for increasing wanted movements while focusing on restricting unwanted movement. If, for example, the mouth moves whenever the eyes blink voluntarily, facial retraining techniques will teach the patient to slowly close the eyes while actively focusing on keeping the mouth muscles still. Facial retraining has shown to be very successful with almost a 60-70% average decrease in synkinesis reported after 7 monthscite journal |author=Brach JS, VanSwearingen JM, Lenert J, Johnson PC. |title=Facial neuromuscular retraining for oral synkinesis. |journal=Plast Reconstr Surg. |volume=99 |issue=7 |pages=1922–31 |year=1997 |pmid=9180715 |doi=10.1097/00006534-199706000-00017] .

Biofeedback

Biofeedback therapy for facial synkinesis aims to increase the patient’s awareness of the facial muscle posture and movement. Facial muscles contain few to none intrinsic muscle sensory receptors (used for proprioceptive feedback) and additionally they do not span movable joints and so lack joint receptors (another source for proprioceptive feedback) . Thus, biofeedback allows the patient to actively sense the motion of their muscles. The two common forms of biofeedback used are electromyographic feedback and mirror feedback. Electromyographic feedback includes visual EMG signals (coming from facial muscle sites displayed to the patient from a computer in the form of waveform traces) or auditory signals that indicate strength of muscle contraction [cite journal |author= Brudny J, Hammerschlag PE, Cohen NL, Ransohoff J. |title= Electromyographic rehabilitation of facial function and introduction of a facial paralysis grading scale for hypoglossal-facial nerve anastomosis. |journal=Laryngoscope. |volume=98 |issue=4 |pages=405–10 |year=1988 |pmid= 3352440 |doi= 10.1288/00005537-198804000-00010] . The subsequent role of the patient is to control the movement of undesired muscle during volitional movement by incorporating the information perceived through the EMG. While mirror feedback is a much more basic way of providing the patient feedback on muscle movement, studies have shown that both are very effective options for synkinesis/paresis reduction [cite journal |author=Ross B, Nedzelski JM, McLean JA. |title=Efficacy of feedback training in long-standing facial nerve paresis. |journal=Laryngoscope. |volume=101 |issue=7 |pages=744–50 |year=1991 |pmid=2062155 |doi=10.1288/00005537-199107000-00009] . Biofeedback is commonly coupled to facial retraining techniques to achieve maximal effectiveness.
A study by Nakamura et. al has shown that biofeedback works better for prevention of synkinesis as opposed to treatment of synkinesis. Due to the extreme efforts needed to achieve improvements during synkinesis, Nakamura et al. observed that patients will often fail to reach their desired goal because of the difficulty of maintaining motivation during training. The desired course of action is to catch the patient shortly after facial nerve trauma and teach the patient biofeedback techniques. This course of action has been experimentally proven to significantly reduce the development of synkinesis.

Mime Therapy

Mime therapy was introduced in the Netherlands in 1980 [cite journal |author=Beurskens CH, Heymans PG. |title=Positive effects of mime therapy on sequelae of facial paralysis: stiffness, lip mobility, and social and physical aspects of facial disability. |journal=Otol Neurotol. |volume=24 |issue=4 |pages=677–81 |year=2003 |pmid=12851564 |doi=10.1097/00129492-200307000-00024 ] . It was initially designed to treat facial palsy by improving symmetry of the face both at rest and during movement. It was then later observed that people who had post-facial palsy synkinesis also benefited from this therapy. It wasn’t until 2003 that Beurskens and Heymans were able to experimentally conclude that mime therapy was indeed a good treatment choice for synkinesis. Furthermore, later studies by Beurskens et al. have shown that benefits obtained from mime therapy are stable 1 year after therapy [cite journal |author=Beurskens CH, Heymans PG, Oostendorp RA. |title=Stability of benefits of mime therapy in sequelae of facial nerve paresis during a 1-year period. |journal=Otol Neurotol. |volume=27 |issue=7 |pages=1037–42 |year=2006 |pmid=17006356 |doi=10.1097/01.mao.0000217350.09796.07] . Current mime therapy consists of a combination of procedures designed to promote symmetry of the face at rest and during movement and control synkinesis. The components include: massage, stretching exercises, exercises to coordinate both halves of the face, etc [cite journal |author=Beurskens CH, Heymans PG. |title=Mime therapy improves facial symmetry in people with long-term facial nerve paresis: a randomised controlled trial. |journal=Aust J Physiother. |volume=52 |issue=3 |pages=177–83 |year=2006 |pmid=16942452] . The overall aim of mime therapy is to develop a conscious connection between the use of facial muscles and emotional expression.So while facial retraining therapy is much more focused on treating slight synkinetic movements, mime therapy aims to increase the overall vigor of the muscles through active exercises, while in the process of doing so, teaching the face to decrease unwanted synkinetic movements.

Botox

Botox is a new and versatile tool for the treatment for synkinesis. Initially used for reducing hyperkinesis after facial palsy [cite journal |author=de Maio M, Bento RF. |title=Botulinum toxin in facial palsy: an effective treatment for contralateral hyperkinesis. |journal=Plast Reconstr Surg. |volume=120 |issue=4 |pages=917–27 |year=2007 |pmid=17805119 |doi=10.1097/01.prs.0000244311.72941.9a] , botox was later attempted on patients with post-facial palsy synkinesis to reduce unwanted movements. The effects of botox have shown to be remarkable with synkinetic symptoms disappearing within 2 or 3 days. Due to the short span of botox effects though, patients must come back to the doctor for re-injection approximately every 3 months. More notable though is that in a majority of patients, various synkinetic movements completely disappeared after 2-3 sessions of botox injections (each session administered after ~3 months) cite journal |author=Ito H, Ito H, Nakano S, Kusaka H. |title=Low-dose subcutaneous injection of botulinum toxin type A for facial synkinesis and hyperlacrimation. |journal=Acta Neurol Scand. |volume=115 |issue=4 |pages=271–4 |year=2007 |pmid=17376126 |doi=10.1111/j.1600-0404.2006.00746.x] . A more specific synkinesis, crocodile tears syndrome (hyperlacrimation upon eating), has been shown to respond exceedingly well to botox injection. Botox is injected directly into the lacrimal gland and has shown to reduce hyperlacrimation within 24-48 hours. The procedure was shown to be simple and safe with very little chance of side-effects (although rarely ptosis can occur due to botulinum toxin diffusion) . Furthermore, reduction in hyper-lacrimation was shown to last longer than the expected 3 months (about 12 months) . Since botox can mimic facial paralysis, an optimized amount of botox has been determined that reduces involuntary synkinesis of the muscle while not affecting muscle tone.

References

ee also

*Facial Palsy
*Paresis
*Paralysis