Aesth. Plast. Surg. 25:73–84, 2001 DOI: 10.1007/s002660010100

© 2001 Springer-Verlag New York Inc.

Botulinum Toxin A and Facial Lines: The Variable Concentration

Claude Le Louarn 59 rue Spontini, 75116 Paris, France

Abstract. Our improved understanding of the functional Migration Factors anatomy of the face and of the action of the botulinum toxin A leads us to determine a new injection procedure which conse- The main concern with the use of toxin A lies in the risk quently decreases the risk of and ptosis, and of migration. Three injection sites are specifically asso- increases the toxin injection’s possibilities and efficiencies. ciated with the risk [6]. Variable toxin injection concentrations adapted to each injected An injection above the eyebrow into the corrugator area are used. Thanks to the new procedure in the upper face, muscle can cause eyelid ptosis. The migration distance toxin A action is quite close to an endoscopic surgical action. between the injection site and the levator palpebrae In addition, interesting results are achievable on the nose, upper muscle is 2 cm. part of the nasolabial fold, jawline and neck regions. Lastly, a An injection in the lateral part of the orbicularis oculi smoothing effect on the skin is obtained by the anticholinergic muscle, just below the eyebrow, can allow the toxin to action of the toxin A on the dermal receptors. migrate into the levator palpebrae muscle or into the . Migration distance is 2 cm. Key words: Botulinum toxin A—Variable concentration— Injection in the upper part of the can Injection technique migrate into the lower part of the frontalis muscle. As described in Fig. 5, lower frontalis muscle paralysis in- duces eyebrow ptosis. Migration distance is 2 cm. Two types of botulinum toxin A are used in this study, The migration is specially due to injection volume, the DYSPORT toxin distributed by BEAUFOUR-IPSEN injection orientation, and injection bleeding. laboratory (Each vial contains 500 Speywood units of toxin A), and the BOTOX toxin distributed by ALLER- Injection Volume GAN laboratory (Each vial contains 100 Allergan units of toxin A). When following the instructions of the Dysport package The toxin equivalence seems to be 3 to 4 Speywood insert, 500 units of Dysport are mixed with 2.5 ml of Allergan unit (Botox) [7]. A Dys- non-preserved saline: 20 units equals a volume of 0.1 ml 1 ס (units (Dysport port vial contains 25% to 40% more usable product than which is frequently larger than the volume of muscle to one Allergan vial. be injected. Obviously, the risk of side effects is high. To correct dystonia and spasm, injections must be re- In order to obtain a more precise effect, the contents of peated at a constant frequency to maintain the desired a vial are diluted in 0.7 ml of saline (nearly a quarter of effect [10]. This seems to be related to the high intensity the recommended quantity) thus the volume to inject will and frequency of stimulation in such disorders. be smaller than the volume of the muscle injected (Fig. In the cosmetic field (facial lines) injection frequency 1). The risk of migration in the periorbital region is thus can be progressively decreased because of 2 factors: a drastically diminished. mild long-term muscle atrophy, and a change in facial For Botox toxin, 100 Allergan units are usually mixed animation patterns with a lower intensity and in the fre- with 4 ml of saline [4]. The proposed dilution is 100 quency muscle nervous stimulation [1,2]. Allergan units mixed with 1 ml of non-preserved saline. The following study describes the new possibilities of It is better to use a 0.5 ml diabetic syringe to inject the botulinum toxin A when using new injection tech- a high concentration solution of toxin A rather than a niques which limit its migration. 1 ml syringe. The 0.5 ml diabetic syringe is twice as 74 Varying Botulinum Toxin A Concentrations

Fig. 1. Volume of 15 units of Dysport in case of dilution of the Fig. 2. The 0.5 ml insulin syringe with 50 units. vial with 2.5 ml, 1.25 ml, 0.62 ml of saline. use of the tip of the thumb and not of its base; lastly, the precise as the 1 ml, but also the 0.07 ml loss of solution unit number in each vial of Dysport or of Botox is subject per use between the syringe and the needle doesn’t exist to a variation of 20%. This unavoidable variation results with the smaller syringe. Indeed, the 0.5 ml diabetic sy- from the toxin manufacturing processes. A good injec- ringe has a 29 gauge needle directly inserted in the cavity tion technique limits problems 1 and 2. with no empty space. The performing syringe we found Variable Toxin Concentration for this use is the BD 4-100 Insulin microfine 8 mm 0.5 ml with 50 units (Fig. 2). The concentration of a motor end-plate near the injection point depends on each type of muscle. A flat and thin Injection Orientation muscle like the platysma muscle has a medium motor end-plate concentration, and, on the contrary, a short and Not only is the bevelled angle of the needle directed to thick corrugator muscle has a high concentration of mo- the desired target exactly like in Collagen injection tech- tor end-plates near the injection point. On this basis, we niques, but also any dangerous adjacent muscle direction describe 3 different toxin concentrations, high, medium of the injection is to be avoided. and low depending upon the action we look for. In case of corrugator muscle injection, the bevelled angle of the needle is directed opposite to the levator The high toxin concentration. 0.7 ml of saline are used palpebrae muscle. to dilute 500 units of Dysport or 1 ml of saline for 100 units of Botox. The action is strong and precise, on thick Bleeding Induced with Injection muscles of the peri orbital area: the corrugator muscle, the pars orbitalis, the depressor A needle injection creates a micro-tissue trauma, micro- supercilii muscle and the lower part of the frontalis bleeding, sometimes an ecchymosis. This ecchymosis muscle. This high concentration diminishes the volume downward migration due to gravity, carries along the of injection and prevents migration. botulinum toxin. This risk is minimized with the help of the following procedure: Any injection on a vascular axis Medium concentration toxin. To obtain a medium con- such as the supraorbital bundle, should be avoided [3]; an centration toxin, two volumes of saline including adrena- appropriate digital pressure is realized when the needle is line is added to the volume of high concentrated toxin removed from the injection site. This action is mainly which is already in the syringe (Fig. 3). important in case of corrugator muscle injection, as well The action is clear and spread over a larger surface as in the case of frontal and orbicularis oculi muscles with the same number of units of toxin. The muscles such as previously described, and in any case of ecchy- concerned are the frontalis, the orbicularis oculi temporal mosis; adrenaline is added to the non-preserved saline and malar pars, the platysma and the muscles. with a dilution of 50 ␮ gr/per ml (like xylocaïne 1% The low concentration toxin. 3 volumes of saline includ- adrenaline). ing adrenaline are added to the volume of toxin already in the syringe. The action of the injection is partial and Injection Technique localised. It is useful for injecting spots in the vermillon border of the or in the orbicularis oculi pars orbitalis There are three causes of the injection imprecision that in the lower eyelid area. The variable concentration can can explain different results with the same patient and be adapted to each physician’s experience and to each the same technique at different injection sessions: a par- patient’s reaction. A patient with a long duration effect allax error vision due to an axis of vision which is not on the periorbital area and too short an effect on the perpendicular to the axis of the syringe; imprecision in frontal area, will benefit from a higher concentration of the digit pressure on the piston of the syringe due to the toxin injection in the frontal area at a further session. C. Le Louarn 75

Seven to 14 units of Dysport or 3 to 5 units of Botox are injected. The tip of the needle is on the arcus super- ciliaris bone, the bevelled opening oriented to the gla- bella area and not to the levator palpebrae muscle. The bony insertion of the muscle is injected, not its skin insertion. The injection of the medial part of the corru- gator muscle decreases the vertical glabella lines. Injection of the lateral part of the corrugator muscle. This injection is realized in case of non-sufficient action of the injection of the medial part of the corrugator muscle to decrease the glabella frown lines, or too low a location of the middle third of the eyebrow. This injec- tion produces the elevation of the middle third of the Fig. 3. The sterile cap of the syringe is filled with the same and eyebrow. The product is injected deeply, near the bone at volume solution of saline, plus adrenaline, used to dilute the the lateral extremity of the corrugator muscle, which toxin. The syringe is filled with the necessary amount and means at the lateral extremity of the bony arcus super- volume of toxin to weaken the target muscles. Two volumes of ciliaris. That is also the lateral extremity of the corruga- the saline are added to the syringe to obtain medium- tor dimple. Only 3 units of Dysport or 1 unit of Botox are concentration toxin, and 3 volumes of saline are added to the used. This very small quantity of toxin will not concern syringe to obtain a low-concentration toxin. In special cases the overlying frontalis muscle. The injection is far from (alcoholism or diabetes, for instance) dilution can be more the and its vacular bundle, a source of important—five times the volume already in the syringe may possible hematoma and migration. be needed.

Injection sites Depressor supercilii muscle The depressor supercilii muscle originates from the nasal The injection sites we are going to study are periorbital process of the nasal portion of the , 1 cm and peribuccal (Fig. 4). above the medial canthal ligament. The belly is oriented transversally and located behind the orbicularis oculi Periorbital Sites muscle. The depressor supercilii muscle penetrates the skin of the top of the eyebrow. Its contraction depresses Periorbital sites include the following muscles: corruga- the head of the eyebrow. Consequently, its injection tor, depressor supercilii, procerus, frontalis, and orbicu- slightly elevates the head of the eyebrow. The tip of the laris oculi. needle penetrates 2 mm behind the orbicularis oculi muscle plane. Three units of Dysport or 1 unit of Botox Corrugator muscle. The corrugator muscle originates are used. from the bone of the lower part of the arcus superciliaris. The volume of the arcus superciliaris depends on the strength of the contraction of the underlying corrugator muscle. A strong contraction creates a progressively The procerus muscle originates from the of more important volume of the arcus superciliaris. The the transverse nasalis, from the periosteum of the nasal palpation of the arcus superciliaris gives information on bones and the perichondrium of the upper lateral carti- the location and strength of the corrugator muscle. The lages. The muscle inserts in the skin over the lower re- muscle belly is oriented transversally and inserted in the gion of the between the . The procerus skin above the eyebrow, creating the characteristic “cor- muscle contraction is responsible for the transverse radix rugator dimple” on a forceful contraction, at the junction lines. The injection is placed in the vertical fibers of the middle third, lateral third of the eyebrow [9]. The middle belly of the muscle. The tip of the needle penetrates 2 third of the eyebrow is then strongly depressed. mm at the root of the nose. Seven units of Dysport or 2 units of Botox are used. Injection of the medial part of the corrugator muscle. From an aesthetic point of view, the induction of medial Frontalis muscle brow ptosis from vertical glabella frown lines treatment should be avoided. This side effect results from the cor- The frontalis muscle originates from a split in the galea rugator muscle injection through the frontalis muscle. In under the anterior hairline and inserts into the forehead this usual technique the frontalis muscle receives com- skin just above the eyebrow. At this level, corrugator, pulsorily some of the injected product and thus is weak- orbicularis oculi, procerus and depressor supercilii ened. In order to avoid this common problem, injection muscles are mixed with the frontalis muscle. Physiologi- into the deep corrugator muscle is realized while the cal studies have determined three vertical, functional, surgeon’s digit raises the medial part of the eyebrow, independent units on each frontalis muscle (right and through the orbicularis oculi muscle. left): medial, medium, and lateral [5]. 76 Varying Botulinum Toxin A Concentrations

Fig. 4. Approximate areas of injection of Botulinum Toxin: h (orange dots) are areas of high toxin concentration, m (blue dots) areas of medium toxin concentration, l (yellow dots) areas of low toxin concentration. The location of each injection point depends on static and dynamic study of the patient. Each injection point is useful for various problems. (Note: not all of these injections can be performed on one patient.)

As demonstrated in Fig. 5, the contraction of the upper tion in the frontalis muscle above this area would in- part of the frontalis muscle moves forward the anterior crease this local concavity. Association of the medial hair line and the contraction of the lower part elevates the eyebrow depression with important elevation of the me- eyebrow. dium third of the eyebrow creates the Mephisto look. In Toxin injection of the frontalis muscle in its lower part order to avoid the Mephisto look when injecting the eye- favors brow ptosis. Toxin injection in its upperpart fa- brow depressor muscles the lateral frontalis muscle must vors fading of the upper frontal rythids without inducing also be injected to minimize the eyebrow medium third brow ptosis. Fading of the rythids of the lower part of the elevation, and no frontalis muscle injection should be frontal area can be decided during a further injection done above the supra-orbital nerve bundle (to avoid eye- session, when elevation of the eyebrow is sufficient and brow head depression). authorizes injection of the lower part of the frontalis Injections of the medial part of the frontalis muscle, muscle. associated with procerus muscle injection, fades medial In most cases, the eyebrow line presents a mild degree frontal lines. These medial injections are safe, without of concavity at the supra orbital notch level. Any injec- any side effects. One unit of Botox or 3.5 units of Dys- C. Le Louarn 77

Fig. 5. Patient with a post-traumatic frontal paralysis of his right side. The lift frontalis muscle contraction creates the elevation of the eyebrow in its lower part and the descent of the hairline in its upper part. Fig. 6. (A) A 43 year-old woman, pre-injection, at rest. (B) Aspect 2 months post-injection with elevation of the eyebrows, fading of the frontal rythids, and disappearance of the excess of skin. Fig. 7. (A) A 40 year-old woman’s pre-injection aspect with this permanent frontal contraction. (B) 2 months post-injection with the frontal rythids fading, and a good design in the eyebrow arch. Fig. 8. (A) A 68 year-old woman, pre-injection, at rest with frontal rythids, eyebrows located low on her face, and crows feet. (B) 2 months post-injection with elevation of the whole eyebrow. Frontal and temporal area are cleaned. 78 Varying Botulinum Toxin A Concentrations

Fig. 9. (A) A 55 year-old woman, pre-injection. She had a face lift 8 years ago and asked for a new face lift. (B) 2 months post-injection, without any additional surgery. The entire face is improved, and the eyebrows are well located with elevation of their inner part.

Fig. 10. (A) A 45 year-old woman with this permanent facial months post-injection with correction of each abnormal eye- mimic: elevation of the right eyebrow, lowering of the inner brow position. The harmony of the face is improved. part of the left one, and frontal, and crows feet rythids. (B) 2

port are used in each injection site. Vertical veins have to be checked before injection so as not to create a hema- toma.

Orbicularis oculi muscle

The orbicularis oculi muscle is divided in three parts, the orbital portion, the preseptal portion, and the pretarsal portion. The orbital portion extends superiorly from above the eyebrow, 3.4 cm lateral to the lateral canthus, and inferiorly far down onto the cheek. The orbital por- tion is the sphincter of the eye. The preseptal and the pretarsal portions have finer muscular fibers involved in the blink reflex. Injection of the pars orbitalis in its lateral portion 1 mm deep fades the crowfeet rythids, and, in its cheek Fig. 11. Dissection of the levator cutaneous malaris muscle. portion, diminishes low located crowfeet rythids. C. Le Louarn 79

Fig. 12. (A) A 49 year-old woman with a plunging tip, a nasolabial fold, and a short upper lip. (B) Aspect 2 months post-injection: the paralysis of the levator labii oris alaquae nasi induces the tip elevation, and improves the nasolabial fold, and the upper lip.

Injection of the orbicularis oculi muscle in its lateral associated with the contraction of the levator labii supe- part can be done just beneath the eyebrow tail to induce rioris muscle (Fig. 11). its moderate elevation. To avoid medial migration to the levator palpebrae muscle, the injection point has to be as lateral as possible under the eyebrow tail. One unit of Peribuccal Sites Botox or 3.5 units of Dysport are used. Two to eight injection points of toxin are realized in each crowfoot area in one or two parallels rows, depend- Peribuccal sites include the following muscles: levator ing on the number and length of wrinkles. The medial labii oris alaquae nasi, dilatator naris, constrictor naris, injection row is at least 1 cm from the lateral orbital rim. depressor anguli oris, orbicularis oris, depressor labii in- Deep injection in the cheek area at the bony insertion ferioris, , and platysma. of the zygomaticus muscle, decreases its contraction. It can be useful in reducing the effects of broad smiles on Levator labii oris alaquae nasi. This muscle originates the recruitment of the lower eyelid and cheek rythids. from the frontal process of the bone and inserts Injection intradermally made in the preseptal portion into the skin of the posterior part of the nostril. The of the lower eyelid reduces those specific fine wrinkles. muscle is the medial part of the To avoid creating on ectropion, the high concentration measure. injection is here changed for a low concentration injec- Its contraction elevates the nostril vertically, deepens tion. Seven units of Dysport or 2 units or Botox are used the upper part of the nasolabial fold, and makes the tip of for each lower eyelid area. the nose plunge. When the contraction of this muscle is Indications in lower eyelid wrinkles with no real ex- associated with the transverse contraction, cess of skin or of fat are: either wrinkles are appearing oblique wrinkles of the nasal bones are obtained. and surgery is no longer necessary, eyelid surgery has The injection is made 1 cm under its bony insertion. already been done and there is no more excess of skin One unit of Botox or 3.5 units of Dysport are used. The and fat but, loss of skin elasticity creates fine wrinkles, or effect on the shape of the nose is obvious in Fig. 12, a furrow between the orbicularis oculi muscle septal part without any other treatment. An injection test before and the inferior orbital rim induced by lower eyelid sur- nose surgery is done to be sure the levator labii oris gery, including fat removal. Toxin injection fades the alaquae nasi muscle section has to be realized. orbital contour and improves the aesthetic result. For examples, see Figs. 6–10. To decrease the depth of the tear-trough, 3 units of Dilatator naris muscle Dysport or 1 unit of Botox are injected in its lower relief. The lower relief of the tear-trough is due to the volume of the muscle. This muscle originates from the frontal The dilatator naris muscle originates from the nasolabial process of maxilla bone, crosses over the medial canthal fold and inserts at the inferior border of the nostril. Its ligament, and inserts into the skin of the lateral and in- contraction increases the frontal diameter of the nostril. ferior quarter of the malar area. The contraction of this The injection is realized in the medial part of the nostril. individualized part of the orbicularis oculi muscle is ef- One unit of Botox or 3.5 units of Dysport are used. The fective on forcefull elevation of the malar area (Clint frontal diameter of the nostril is decreased and the usual Eastwood mimic) and creates the submalar dimple. The surgical incision at the nostril base can be avoided (Fig. contraction of this levator cutaneous malaris muscle is 13). 80 Varying Botulinum Toxin A Concentrations

Fig. 13. (A) This is a patient seeking . (B) Post tion of the depressor anguli oris muscle, associated with the operative result. (C) The patient was happy with her result, but contraction of the mentalis muscle. This combined contraction she desired to diminish her alar base. The usual alar base re- creates the typically sulky look. (B) Injection of the upper part section was not possible because of the patient’s tendency to- of the mentalis muscle, and the main part of the depressor ward hypertrophic scars. (D) Injection of the dilatation naris anguli oris muscle, advances the chin and elevates the corner of muscle shortened her alar base. the mouth. Underlying wrinkles have disappeared. The vermil- Fig. 14. (A) A 55 year-old woman with a permanent contrac- lon border, injected, is also improved.

Constrictor naris muscle projecting the upper lip. One unit of Botox or 3.5 units of Dysport are used. The constrictor naris muscle originates from the bony process of the dentis canini and inserts into the posterior Depressor anguli oris muscle border of the nostril. Its contraction lowers the nostril and decreases its sagittal diameter. Consequently, the The depressor anguli oris muscle originates from the upper lip anterior projection is increased. Its injection is middle part of the linea obliquae mandibula and runs into useful to elevate the nostril insertion and to diminish a the skin in the corner of the mouth. The anterior skin permanent contraction of the constructor naris muscle insertion of its belly fibers creates the bitterness furrow. C. Le Louarn 81

Fig. 15. (A) A 52 year-old woman, pre-injection. (B) The injection of the vermillon border decreases the importance of the peribuccal wrinkles.

An injection is made in the body of the muscle, lateral lower lip and the whole chin skin. If a patient has a flat to the bitterness furrow and at mid-height, between the chin due to a constant mentalis muscle contraction, su- mandibular border and the corner of the mouth. A second perficial medial injections in the upper part of the muscle injection can be done near its bony insertion on the linea maintains the lower part contraction and creates a chin obliquae mandibula. This toxin injection lightly lifts the advancement with softening of the skin of the upper part corner of the mouth and decreases the sad appearance of of the mentalis area. the bitterness furrow. One unit of Botox or 3.5 units of A common type of chin mimic is the mentalis muscle Dysport are used on each injection site (Fig. 14). An contraction and contraction of the two depressor angu- injection that is too high near the corner of the mouth can loris muscles. When these three muscles are injected induce an paralysis causing feed- (Fig. 13) the sulky look disappears. ing difficulties. Too medial an injection could induce a depressor labii Platysma muscle inferioris muscle paralysis causing speaking difficulties. The platysma muscle originates from the superficial fas- Orbicularis oris muscle cia of the upper chest, clavicle, and acromial regions. The posterior fibers of the muscle are forward and blend To minimize functional problems and to improve the with the depressor anguli oris, the , and the lateral aesthetic result, a toxin injection is made in the vermillon part of the orbicularis oris muscles to terminate in the border exactly like a collagen injection. The low concen- skin of the oral commissure. The anterior medial fibers tration solution is used and three to four injection points insert into the periosteum of the medial part of the body are used in each lip. of the . It is these anterior fibers that cause One unit of Dysport or 0.3 units of Botox are used on medial bands when platysma muscle contracts. Three to each injection point. Those injection points are made at five injections are spaced vertically at 1.5 cm intervals least 1.5 cm from the corner of the mouth to eliminate from the jawline to the lower neck, in each band. feeding problems (Fig. 15). Injections can be made in a necklace pattern across the platysma. Currently, the two large platysma bands pre- Depressor labii inferioris muscle sent in most patients are injected with up to 60 units of Dysport or 20 units of Botox each (Fig. 17). Only a few The depressor labii inferioris muscle originates from the number of units can be injected above the chin/cervical medial part of each linea obliquae mandibula and inserts angle to prevent migration to the deglutition muscles. in the whole chin skin. Its contraction depresses the me- As stated by Matarasso et al., conditions such as dial part of the lower lip, lowers and spreads laterally the lipodystrophy, cutaneous laxity, and extremely flaccid whole chin skin. If a patient has a permanent and strong muscle cords are not appropriate for consideration [8]. concentration of the depressor labii inferioris muscle, a Those authors report an elevation of the lower face after witch chin appears. To cure this spasm, injections of platysma cords injection. However, patients in this series Botulinum Toxin A are located in the cutaneous chin had multiple sites on the face injected with the maximum insertions of the muscle, specifically laterally (Fig. 16). total dose of 400 units of Botox (near 1200 units of Dysport). Mentalis muscle Skin Softening The mentalis muscle originates from the bony process of the dentis incicivi and caninini and inserts into the whole The botulinum toxin injection improves the aspect of the chin skin. Its contraction elevates the medial part of the skin. The toxin blocks eccrine sweat glands which are 82 Varying Botulinum Toxin A Concentrations

Fig. 16. (A) A 52 year-old woman with a permanent contraction of the depressor labii inferioris muscle which creates a witch chin. The patient underwent many operations to try to solve this problem. (B) 2 months post-injection. Toxin (20 units of Dysport or 6 units of Botox, medium concentration) injections advance and relax the chin, and hyaluronic acid (Perlane, Q-Med Laboratory) injections fill the residual posterior depression.

Fig. 17. (A) A 49 year-old woman before injection in her platysma bands. (B) The platysma result post-injection. innervated by cholinergic sympathetic nerve fibers. This year. Three quarters of the patients received injections of effect is used to treat focal hyperhydrosis. Apocrine Dysport for 4 years. Eighty-nine percent of the patients sweat glands, supplied by adrenergic sympathetic nerve are women, and eleven percent are men. The mean age fibers remain unaffected by botulinum toxin. This anti- treated was 45 for woman, and 40 for men. Neither topi- cholinergic dermal effect of the botulinum toxin, associ- cal anesthesia or oral anxiolytics were used. Clinical ex- ated with an action on the skin trophicity, explains the amination of the patient is done at rest and during the smooth skin aspect obtained after injection. A mild and mimic. Pictures are taken at each session. diffuse effect can be obtained on the skin of the jaw without paralysing the sublying muscles with a very low Injection frequency concentration of the toxin. Injections are usually made every 3–5 months. Result Patients and methods stability can be obtained after 5–10 sessions. A stable result is defined as the disappearance of the injected This study includes 613 patients. One quarter of the pa- area’s wrinkles for a long period of time. Result stability tients were treated with toxin injection of Botox for one depends on each patient and also on each muscular area. C. Le Louarn 83

Fig. 18. (A) A 55 year-old woman before a lower face lift surgery and an upper face toxin injection. (B) Frontal wrinkles have disappeared and the whole face is harmoniously younger.

In our experience, factors that have influenced the result ful to complete an endoscopic surgery. Harmonization of stability are: sex of patient (better stability for women), the whole face after a cervical and jugal lift can be ob- skin thickness (better with thin skin), facial expression tained when injecting the frontal area with toxin. Abra- pattern (better with moderate facial expression patterns) sion or chemabrasion, more devoted to treat actinic and patient activity (better with non-athletic patient). wrinkles, can be used along with toxin injection to treat Sex and skin thickness are generally related. Patients dynamic wrinkles and to obtain a more complete result. with extreme facial expressions or who are very active Fat grafting in mobile areas, like the vermillon border is are trained to control the muscles. A fifth factor that helped by pre-treatment with toxin. increases the result stability is the peripheric neuropathy induced by even a moderate alcoholism. Regarding muscular areas, the interbrow muscular Complications area can be stabilized in one patient at the fourth injec- tion session although in the same patient the orbicularis oculi muscle can still noticeably contract two months Immunization. As stated by Matarasso [8], to avoid the after the last injection. Doses in this area have to be potential complication of immunization it is important to increased for a larger period to obtain the desired effi- use the smallest possible effective dose, extend the in- ciency. After each session, patients are asked to move the terval between treatments (at least 3 months), and avoid injected muscles vigorously in the following days in or- booster injections. One case was reported in the glabella der to favor toxin fixation on those motor end plates. area after frequent booster injections. Neutralizing anti- Contraindication for use of botulinum toxin include: bodies last for at least ten years. pregnancy or attempts at pregnancy, quinine, calcium channel blockers, penicillamine, aminoglycosid antibiot- Migration. This is a temporary complication that can ics (they can potentiate the effects of botulinum toxin), cause browptosis, blepharoptosis, lagopthtalmia, and ec- preexisting neuromuscular conditions like Myasthenia tropion. Blepharoptosis can be partially cured with eye- Gravis or Eaton Lambert syndrome, and peripheric neu- drops containing an adrenergic agent like neosynephrin. ropathy, such as diabetes, or alcoholism (neuropathies A temporary contraction of Muller’s muscle elevates the only need one third of the typical quantity). upper eyelid margin. A specific ocular complication us- Botulinum toxin has to be an adjunctive treatment in ing an adrenergic agent includes glaucoma. A consulta- facial aesthetic surgery and medicine. Stabilization in tion with an ophthalmologist is mandatory before using good position of the frontal endoscopic lift is favored by neosynephrin. a presurgical treatment with toxin injection of depressor muscles and of the upper part of the frontalis muscle. The only risk is that the patient may be pleased by the results Dysphagia. There have been 718 cases of adverse reac- of this treatment, and may therefore cancel the surgical tions to the generally approved use of Botox made to the appointment. Of course, toxin injection can also be use- FDA between 1989 and 1997. Of these cases 142 were 84 Varying Botulinum Toxin A Concentrations qualified as serious. They are mainly dysphagia. The References potential gravity of the dysphagia suggests it is wise to decrease the doses injected to treat platysma bands, al- 1. Carruthers JDA, Carruthers JA: Treatment of glabellar though Matarasso et al. [8] describe no migration of the frown lines with clostridium botulinum A-exotoxin. J Der- matol Surg Oncol 18:17, 1992 50 to 100 units of Botox injected in the neck to the 2. Duchen LW: An electron microscope study of the changes deglutition muscles. induced by botulinum toxin in the motor end plates of slow and fast fibers of the mouse. J Neurol Sci 14:47, 1971 Poisoning. Not a single case of poisoning by intravas- 3. Fagien S: Botox for the treatment of dynamic and hyper- cular injection with the doses used for facial rejuvenation kinetic facial lines and furrows: adjonctive use in facial has been reported. The median lethal dose is estimated to aesthetic surgery. Plast Reconstr Surg 103:701, 1999 be one hundred times larger than the maximum total 4. Klein AW: Dilution and storage of botulinum toxin. Der- recommended dose for one session. matol Surg 24:1179, 1998 5. Le Louarn C: Chirurgie esthe´tique faciale par la voie d’abord palpe´brale supe´rieure. Journ Franc ORL 45:297, Dry eye syndrome. Worsening of a dry eye syndrome is 1996 encouraged by the anticholinergic effect of the toxin on 6. Le Louarn C: Toxine botulique et rides faciales: une nou- the lacrymal gland. velle proce´dure d’injection. Ann Chir Plast Esthe´tique 43(5):526, 1998 7. Marion MH, Sheely M, Sangla S, Soulayrol S: Dose stan- Conclusion dardization of botulinum toxin. J Neurol Neurosurg Psy- chiatry 59:1, 1995 Thanks to an improved understanding of the functional 8. Matarasso A et al.: Botulinum A-exotoxin for the manage- anatomy, a performing syringe, the addition of adrena- ment of platysma bands. Plast Reconstr Surg 103:645, 1999 line to the saline solution making the use of digital pres- 9. Rollin KD, Landon B: Endoscopic forehead lift: anatomic sure more precise, and the variable concentration provid- basis. Aesthetic Surg Journ 17:97, 1997 ing the ability to adapt the number of toxin units to the 10. Scott AB: Botulinum toxin injection in the extraocular type of muscle and to the desired effect, we have a better muscles as an alternative to strabismus surgery. Ophthal- and more reliable result. mology 87:1044, 1980