Clin. Otolaryngol. 1992, 17, 223-224
Management of facial synkinesis with Clostridium botulinum toxin injection R.E.MOUNTAIN, J . A . M . M U R R A Y & A.QUABA* Otolaryngology Unit, The Royal Injirmary, Edinburgh and *Department of Plastic Surgery, Royal Hospital for Sick Children, Edinburgh, UK Accepted for publication 5 September 1991 M O U N T A I N R . E . , M U R R A Y J.A.M. & Q U A B A A .
(1 992) Clin. Otolaryngol. 17, 223-224
Management of facial synkinesis with Clostridium botulinum toxin injection Associated movements after facial paralysis (synkinesis), due to unphysiological co-innervation of the facial muscles, often complicates the rehabilitation of patients following facial palsy. Clostridium botulinum toxin is a neurotoxin that interferes with the release of acetylcholine from motor nerve end plates, causing skeletal muscular paralysis. This paper concentrates on its clinical use in treating synkinesis affecting orbicularis oculi function and documents the results of treatment in 4 patients. Control of synkinesis, achieved in all 4 patients, was effective within a few days and lasted for 4-6 months. 2 patients developed transient diplopia and ptosis shortly after injection. However, no lasting complications or systemic side-effects were noted. All patients reported a significant improvement in their symptoms and reinjection at 7 months was carried out successfully. Keywords
synkinesis
facial palsy
botulinum toxin
It is generally accepted that facial synkinesis following facial paralysis is due to unphysiological co-innervation of facial muscles resulting from misdirected axonal sprouting. Synkinetic movement, such as narrowing of the palpebral fissure when moving the lips, smiling or chewing, is often observed 12-18 months after the onset of paralysis and usually occurs when more than 95% of nerve fibres have degenerated.' Electromyography (EMG) reveals that motor units discharge in perfect synchrony and provides electrophysiological proof that the sprouts of a single regenerating axon can innervate different groups of facial muscles. Previously, the only way to treat periorbital synkinesis was to surgically denervate all fibres supplying the orbicularis oculi muscle. Following the pioneering work of Scott et aL2 who first instituted the clinical use of Clostridium botulinum A to cause selective denervation of skeletal muscle, it has been used successfully in the treatment of strabismus, blepharospasm, hemifacial spasm, torticollis, spastic entropion, spastic dysphonia and post-facial palsy synkinesis. Clostridium botulinum toxin is a powerful neuroparalytic toxin which is strongly hydrophobic and, when injected Correspondence: Dr R.E.Mountain, Otolaryngology Unit, Lauriston Building, The Royal Infirmary, Edinburgh EH3 9EN, UK.
locally into skeletal muscle, binds strongly to motor nerve end plates, is internalized, and disrupts Ca2+ mediated release of acetylcholine, thereby causing a temporary paralysis of the affected m ~ s c l e . ~ Two other mechanisms of action have been proposed, though not scientifically proven. The toxin may affect intrafusal muscle fibres in the proprioceptive spindles, modifying spindle efferent discharges, thereby reducing muscle tone. The other mechanism may involve retrograde intra-axonal flow to the motor cell body, directly affecting nuclear f~nction.~ Six different toxins have been serologically isolated (A-F) but only type A has been used clinically.
Patients, materials and methods Four patients with significant post-facial palsy synkinesis were treated with local periorbital injection of botulinum toxin. They were reviewed at 1 week, 1 month and 4 months and all had repeat injections performed at 7 months. Botulinum toxin prepared by the vaccine research and production laboratories, Porton Down, Salisbury was used and diluted with normal saline to give a concentration of 5 ng/ml (toxin-haemagglutinin complex) equivalent to 200 mouse units (LD,, of botulinum type A toxin).
223
224 R.E.Mountuin et al.
0
4
0.1 ml
Figure 1 . Sites of injcctlon of botulinum toxin (left eye). The periorbital skin was cleaned with alcohol and 3 injections of toxin were given subcutaneously and intramuscularly on the ipsilateral side, using a tuberculin syringe and 30 g needle (Figure I). All 4 patients reported a subjective improvement in their symptoms, the mean interval between injection and relief of spasm being about 3 days. Pre and post-injection photographs were taken to give an objective evaluation of treatment. In all cases, a gradual reduction in effect was noted over an 18 week period, and all patients had reinjection performed at 7 months. Half the dose of toxin was used for the repeat injection and 3 of the patients reported a good result following repeat treatment, with one patient reporting no significant improvement following the second injection. Side-effects reported included ptosis (2), diplopia (2), epiphora (1) and headache (I). All reported side-effects lasted for only I 2 months and no systemic side-effects were reported (dysphagia, respiratory symptoms, paralysis).
Discussion The use of botulinum toxin A in the treatment of hemifacial spasm,’ blepharospasm6 and a wide variety of involuntary facial movement disorders?’ is well documented as being a safe, effective means of controlling involuntary facial movement. Enthusiastic reports of its use in the treatment of postfacial palsy synkinesis have been documented by Biglan and May’ (20 cases) and by Elson ( 5 cases).‘ N o systemic side-effects have been reported, yet a high percentage of patients have experienced transitory ptosis, diplopia and excessive tearing. Ptosis is caused by spread of
the toxin to the levator palpebrae superioris, which appears to be particularly sensitive to the toxin. The inferior oblique muscle is also susceptible to spread of toxin, producing vertical strabismus. Epiphora is thought to be due to increased lower lid laxity.6 Botulinum toxin can be accurately measured and small doses injected locally into muscle causing a local flaccid paralysis, without systemic toxicity. Muscle function usually returns slowly over a few months as new end plates are formed by sprouting axons, and usually muscular function returns at about 4-6 months. Repeat injections of toxin are possible usually using a reduced dose and previous studies have shown no systemic antibody response to repeat inje~tion.~ The dose of botulinum toxin A can be expressed in mouse LD, units, ng of toxin-haemagglutinin complex, or ng of neurotoxin. 1 ng of UK toxin-haemagglutinin complex contains 40 mouse units. However, 1 ng of American toxin -haemagglutinin complex is stated to contain 2.5 mouse units.8 This very significant difference in toxicity has been observed clinically and, therefore, great care must be taken in correctly preparing dosages for clinical use.
References 1 MAYM. (1986) In The Facial Nerve, pp. 510-511. Thienie Inc, New York 2 SCOTT A.B., ROSENBAUMA. & COLLINSC.C. (1973)
Pharmacological weakening of extra-ocular muscles.
Invrst.
Opthabnnl. Vis. Sri. 12, 924-927 3 MELLINC J., HAMBLETON P. & Skt0h.E C.C. (1988) Clostridium botulinum toxins: Nature and preparation for clinical use. Eye 2,
16-23 ELSTOHJ.S. (1988) Botulinum toxin therapy for involuntary facial movement. Eye 2, 12-15 5 Dt;. VHIESEP.P. (1988) Treatment of hemifacial spasm with botulinum A toxin. Proceeclinxs oJ the Sixth International Symposium on the Facial Nerve, p. 85. Kugler & Ghedini. Rio de Janeiro, Brazil with botulinum toxin on neurogenic blepharospasm. Er. Med. J .
4
290, 185771859 7 BIGLANA.W., MAY M. & Bow~asR.A. (1988) Management of facial spasm with Clostridium botulinum toxin, Type A (oculinium).Arch. Otolarvngol. Head Neck Surg. 114, 1407-1412 8 Q U I N N N. & HALLETT M. (1989) Dose standardisation of botulinum toxin. Lancet 29, 964
Management of facial synkinesis with Clostridium botulinum toxin injection R.E.MOUNTAIN, J . A . M . M U R R A Y & A.QUABA* Otolaryngology Unit, The Royal Injirmary, Edinburgh and *Department of Plastic Surgery, Royal Hospital for Sick Children, Edinburgh, UK Accepted for publication 5 September 1991 M O U N T A I N R . E . , M U R R A Y J.A.M. & Q U A B A A .
(1 992) Clin. Otolaryngol. 17, 223-224
Management of facial synkinesis with Clostridium botulinum toxin injection Associated movements after facial paralysis (synkinesis), due to unphysiological co-innervation of the facial muscles, often complicates the rehabilitation of patients following facial palsy. Clostridium botulinum toxin is a neurotoxin that interferes with the release of acetylcholine from motor nerve end plates, causing skeletal muscular paralysis. This paper concentrates on its clinical use in treating synkinesis affecting orbicularis oculi function and documents the results of treatment in 4 patients. Control of synkinesis, achieved in all 4 patients, was effective within a few days and lasted for 4-6 months. 2 patients developed transient diplopia and ptosis shortly after injection. However, no lasting complications or systemic side-effects were noted. All patients reported a significant improvement in their symptoms and reinjection at 7 months was carried out successfully. Keywords
synkinesis
facial palsy
botulinum toxin
It is generally accepted that facial synkinesis following facial paralysis is due to unphysiological co-innervation of facial muscles resulting from misdirected axonal sprouting. Synkinetic movement, such as narrowing of the palpebral fissure when moving the lips, smiling or chewing, is often observed 12-18 months after the onset of paralysis and usually occurs when more than 95% of nerve fibres have degenerated.' Electromyography (EMG) reveals that motor units discharge in perfect synchrony and provides electrophysiological proof that the sprouts of a single regenerating axon can innervate different groups of facial muscles. Previously, the only way to treat periorbital synkinesis was to surgically denervate all fibres supplying the orbicularis oculi muscle. Following the pioneering work of Scott et aL2 who first instituted the clinical use of Clostridium botulinum A to cause selective denervation of skeletal muscle, it has been used successfully in the treatment of strabismus, blepharospasm, hemifacial spasm, torticollis, spastic entropion, spastic dysphonia and post-facial palsy synkinesis. Clostridium botulinum toxin is a powerful neuroparalytic toxin which is strongly hydrophobic and, when injected Correspondence: Dr R.E.Mountain, Otolaryngology Unit, Lauriston Building, The Royal Infirmary, Edinburgh EH3 9EN, UK.
locally into skeletal muscle, binds strongly to motor nerve end plates, is internalized, and disrupts Ca2+ mediated release of acetylcholine, thereby causing a temporary paralysis of the affected m ~ s c l e . ~ Two other mechanisms of action have been proposed, though not scientifically proven. The toxin may affect intrafusal muscle fibres in the proprioceptive spindles, modifying spindle efferent discharges, thereby reducing muscle tone. The other mechanism may involve retrograde intra-axonal flow to the motor cell body, directly affecting nuclear f~nction.~ Six different toxins have been serologically isolated (A-F) but only type A has been used clinically.
Patients, materials and methods Four patients with significant post-facial palsy synkinesis were treated with local periorbital injection of botulinum toxin. They were reviewed at 1 week, 1 month and 4 months and all had repeat injections performed at 7 months. Botulinum toxin prepared by the vaccine research and production laboratories, Porton Down, Salisbury was used and diluted with normal saline to give a concentration of 5 ng/ml (toxin-haemagglutinin complex) equivalent to 200 mouse units (LD,, of botulinum type A toxin).
223
224 R.E.Mountuin et al.
0
4
0.1 ml
Figure 1 . Sites of injcctlon of botulinum toxin (left eye). The periorbital skin was cleaned with alcohol and 3 injections of toxin were given subcutaneously and intramuscularly on the ipsilateral side, using a tuberculin syringe and 30 g needle (Figure I). All 4 patients reported a subjective improvement in their symptoms, the mean interval between injection and relief of spasm being about 3 days. Pre and post-injection photographs were taken to give an objective evaluation of treatment. In all cases, a gradual reduction in effect was noted over an 18 week period, and all patients had reinjection performed at 7 months. Half the dose of toxin was used for the repeat injection and 3 of the patients reported a good result following repeat treatment, with one patient reporting no significant improvement following the second injection. Side-effects reported included ptosis (2), diplopia (2), epiphora (1) and headache (I). All reported side-effects lasted for only I 2 months and no systemic side-effects were reported (dysphagia, respiratory symptoms, paralysis).
Discussion The use of botulinum toxin A in the treatment of hemifacial spasm,’ blepharospasm6 and a wide variety of involuntary facial movement disorders?’ is well documented as being a safe, effective means of controlling involuntary facial movement. Enthusiastic reports of its use in the treatment of postfacial palsy synkinesis have been documented by Biglan and May’ (20 cases) and by Elson ( 5 cases).‘ N o systemic side-effects have been reported, yet a high percentage of patients have experienced transitory ptosis, diplopia and excessive tearing. Ptosis is caused by spread of
the toxin to the levator palpebrae superioris, which appears to be particularly sensitive to the toxin. The inferior oblique muscle is also susceptible to spread of toxin, producing vertical strabismus. Epiphora is thought to be due to increased lower lid laxity.6 Botulinum toxin can be accurately measured and small doses injected locally into muscle causing a local flaccid paralysis, without systemic toxicity. Muscle function usually returns slowly over a few months as new end plates are formed by sprouting axons, and usually muscular function returns at about 4-6 months. Repeat injections of toxin are possible usually using a reduced dose and previous studies have shown no systemic antibody response to repeat inje~tion.~ The dose of botulinum toxin A can be expressed in mouse LD, units, ng of toxin-haemagglutinin complex, or ng of neurotoxin. 1 ng of UK toxin-haemagglutinin complex contains 40 mouse units. However, 1 ng of American toxin -haemagglutinin complex is stated to contain 2.5 mouse units.8 This very significant difference in toxicity has been observed clinically and, therefore, great care must be taken in correctly preparing dosages for clinical use.
References 1 MAYM. (1986) In The Facial Nerve, pp. 510-511. Thienie Inc, New York 2 SCOTT A.B., ROSENBAUMA. & COLLINSC.C. (1973)
Pharmacological weakening of extra-ocular muscles.
Invrst.
Opthabnnl. Vis. Sri. 12, 924-927 3 MELLINC J., HAMBLETON P. & Skt0h.E C.C. (1988) Clostridium botulinum toxins: Nature and preparation for clinical use. Eye 2,
16-23 ELSTOHJ.S. (1988) Botulinum toxin therapy for involuntary facial movement. Eye 2, 12-15 5 Dt;. VHIESEP.P. (1988) Treatment of hemifacial spasm with botulinum A toxin. Proceeclinxs oJ the Sixth International Symposium on the Facial Nerve, p. 85. Kugler & Ghedini. Rio de Janeiro, Brazil with botulinum toxin on neurogenic blepharospasm. Er. Med. J .
4
290, 185771859 7 BIGLANA.W., MAY M. & Bow~asR.A. (1988) Management of facial spasm with Clostridium botulinum toxin, Type A (oculinium).Arch. Otolarvngol. Head Neck Surg. 114, 1407-1412 8 Q U I N N N. & HALLETT M. (1989) Dose standardisation of botulinum toxin. Lancet 29, 964
