botox boca y cuello

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New Indications for Botulinum Toxin Type Ain Cosmetics: Mouth and NeckM. Matilde M. Spsito, M.D., Ph.D.

So Paulo, Brazil

Botulinum toxin type A is frequently used to smoothhyperkinetic lines in the periocular and forehead areas ofthe upper face, but it has been used less frequently forindications in the lower face and neck. This study was

designed to determine whether botulinum toxin treat-ment of themouth and neck areas is as clinicallysuccessfulas thetreatment of theupper face. This was a retrospectivestudy of patients who were treated with botulinum toxintype A (Botox) to soften hyperkinetic facial wrinkles. Of100 patients randomly selected from a single clinical prac-tice, 91 met the inclusion criteria and were divided intotwo groups for analysis. The 56 patients in group 1 did notreceive treatment in the mouth and neck areas, whereasthe 35 patients in group 2 were treated at least once in themouth and neck areas. Patients were surveyed for periodsranging from 7 to 49 months. Most patients in each grouphad a single botulinum procedure during this period.Both groups of patients had comparable improvement of

wrinkles both at the evaluation immediately after the neu-

romuscular blockade and during follow-up. In compari-son with patients whose treatment was confined to theupper face, patients who received global treatment withbotulinum toxin type A, including injections in themouthand neck areas, were injected in more sites per procedureand had more procedures in combination with other ther-apies. Patient satisfaction with botulinum toxin treatmentand outcomes was high in both groups. Botulinum toxintype A is an important tool within the therapeutic spec-trum for the treatment of hyperkinetic facial wrinkles,including those in the areas of the mouth andneck. (Plast. Reconstr. Surg. 112 (Suppl.): 75S, 2003.)

Hyperkinetic wrinkles result from recurringcontraction of the muscles of expression in theface and neck. They represent a prevalent clin-ical scenario, and patients often look to aes-thetic medicine for resolution. Botulinumtoxin type A has been used in cases of hyperki-netic wrinkles since 1987, when Carruthers andCarruthers1 and Markey2 noted the smoothingeffect of botulinum toxin type A on facial lines

and wrinkles. At first, only the upper third ofthe face was treated; however, with clinical ex-perience, the benefits of treating the mid and

lower thirds of the face were also noted.There are eight different serotypes of botu-linum toxin; type A is the most potent and themost commonly used clinically.3 6 Botox (Aller-gan, Inc., Irvine, Calif.) is a purified botulinumtoxin type A isolated from the controlled fer-mentation of Clostridium botulinum, an anaero-bic bacterium.3 It is a stable, sterile, vacuum-dried powder to be used after dilution withsaline solution without preservatives.7 A differ-ent preparation of botulinum toxin type A(Dysport) is also available but has been usedless often than Botox in aesthetic medicine. Abotulinum toxin type B has recently been ap-proved for the treatment of cervical dystonia insome countries, but there are no publishedreports of the use of this product for faciallines.

Botulinum toxin type A weakens skeletalmuscles by cleaving the synaptosome-associ-ated protein SNAP-25. This blocks the releaseof acetylcholine from the motoneuron and en-ables the repolarization of the postsynaptic ter-minal; as a result, the muscular contraction isblocked.3,4 The blockade of neuromuscular

transmission does not interfere with acetylcho-line production, and the effect is reversible

within months.8

The toxin molecule has a mass of approx-imately 150,000 Da.7 The molecule has twochains. The heavy chain promotes the inter-nalization and activation of the light chain, azinc-dependent metalloprotease that specifi-

From the Department of Medicine, Escola Paulista de Medicina, Universidade Federal de So Paulo. Received for publication November 11,2001.

Originally published in Plastic and Reconstructive Surgery in August, 2002 (Plast. Reconstr. Surg. 110: 601, 2002).

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cally cleaves SNAP-25.3 The toxin molecule isunable to cross the blood-brain barrier;therefore, it has no effect on the centralnervous system.9

Botulinum is not usually measured in nano-grams but in biological units (U), defined by

the median lethal dose in mice. That is, 1 U isthe dose that kills 50 percent of female Swiss-Webster mice weighing 18 to 20 g when in-jected intraperitonially.3 Units are not equiva-lent for the two formulations of botulinumtoxin type A that are commercially available:1 U of Botox is clinically equivalent to 3 to 5U of Dysport. For this reason, it is importantto cite the formulation of botulinum toxintype A used when giving dosages for proce-dures. The Botox formulation of botulinumtoxin type A was used for all procedures de-

scribed in this article.Vacuum-sealed vials containing the neuro-toxin should be kept in a freezer at5C. Theshelf life of Botox described on the label is 2years, but botulinum toxin type A may con-tinue to be stable for up to 4 years when ap-propriately stored.10 Botulinum toxin type A isthermolabile and is also inactivated by pH al-teration.9 After dilution with saline solutionwithout preservatives, the toxin should be usedas soon as possible, but it may be kept in arefrigerator at 2 to 8C for up to 4 hours.3

Refreezing the diluted product results in a de-crease in potency; one study demonstrated thatrefreezing the solution for 2 weeks resulted ina 70 percent loss of potency.3 However, otherstudies have shown that the diluted toxin canbe stored refrigerated for a week or longer withno loss of potency.11,12

The response to botulinum toxin type A isinfluenced by the dosage (dose-dependent ef-fects),3,13 the injection technique, and the size(mass) of the injected muscle. Botulinumshould be used to target specific muscles toproduce sustained yet reversible muscle weak-ening. The effects are typically evident within 3to 10 days after the injection, and they gener-ally last 3 to 6 months.4,14 In open-air applica-tion during blepharoplasty, the effects werenoticed within 24 hours and lasted for 9 to 10months.10 Patients using botulinum repeat-edly over a prolonged period often experi-ence a longer duration of effects of laterprocedures and an increased interval be-tween procedures.1517

Some authors have suggested that a progres-sive improvement of wrinkles may be attrib-

uted to muscular atrophy rather than to pro-longed botulinum toxin type A effects.18 Thesesame authors report clinical resistance to theproduct, with the need for increasing doses toreach the same results,18 but this is not typicallyfound when botulinum toxin type A is used for

cosmetic indications.The occurrence of muscular atrophy with

botulinum toxin type A application is contro-versial. The American Academy of Neurologystherapeutic and technology committee reportrefers to the emergence of fibrosis and atrophyof the orbicularis oculi after botulinum treat-ment in blepharospasm cases.19 Some authorsreport histologic changes for as long as 3 yearsin treated muscles.20 Other authors have sug-gested that there are no significant histologicchanges with long-term use of botulinum.16,2123

Use of botulinum toxin type A is absolutelycontraindicated24 in cases of allergy to the drugor its components, infection at the site of in-jection, pregnancy or breast feeding (categoryC), and in patients with unrealistic expecta-tions or emotional distress.25 It is relatively con-traindicated when associated with neuromus-cular disease or coagulopathy, when thepatient needs his or her total facial expression,when there is no compliance of the patientwith the global proceeding, or when the pa-tient is using drugs such as aminoglycosides

(potentiators for botulinum toxin type A), as-pirin, or nonsteroidal anti-inflammatory drugs(increase the risk of bleeding) within 4 weeksof the procedure.

Potential complications of botulinum toxintype A therapy can be characterized as relative,described, and rare. Relative complications(pain, bruising, sensation of loss of strength,discrete edema, local edema, and infection)are avoidable or easily resolved. Describedcomplications (eyelid ptosis,17,18 eyebrow pto-sis,18 fixed facial expression-mask, asymmetry,18

and functional alteration18) commonly occurbut are generally not problematic for the pa-tient or clinician. These complications canarise from errors in technique, patient selec-tion, dilution, and dosing. They can result ineyelid or eyebrow ptosis, incompetent mouth,or facial asymmetry. On the other hand, pa-tients with facial asymmetry caused by otherdisorders, such as facial nerve trauma and fa-cial paralysis, can be treated with botulinumtoxin type A to restore facial symmetry. Insome of these cases, there is improvement of

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functional activity of the affected area after theprocedure.26

Of the rare complications (allergy, focal at-rophy, altered sweating, antibody formation,27

and diplopia17), antibody formation is particu-larly undesirable because the development of

neutralizing antibodies may lead to loss of theeffect of therapy. Antibody formation occursmore often with botulinum toxin type A injec-tions of doses higher than 200 U, intervalsbetween procedures of 1 month or less, andaccidental intravenous injections.9 Thus, anti-body formation is dose dependent and fre-quency dependent,3 and for this reason, theuse of the lowest dose with proven efficacy isrecommended, with a minimum of 3 monthsbetween procedures.16 Because the doses ofbotulinum toxin type A used for cosmetic in-

dications are small, the risk of antibody pro-duction seems to be minimal. It is important touse saline solution without preservatives to di-lute the toxin.12 The use of distilled water re-sults in painful injections, and the use of solu-tions with preservatives might alter botulinumpotency by altering the pH of the solution. It isalso advisable to avoid bubbling or shaking thevial contents during dilution and recovery ofthe drug to the injection syringe becauserough handling of botulinum could cause itsdenaturation and inactivation. Finally, the con-

tents of the vials should not be used if the vialshave lost their vacuum because toxin stored inthis manner may lose activity.3

Drug dilution should be done in a way thatallows effective control of the administereddose. A large volume favors drug dispersionand should be avoided when targeting smallmuscles.3,28 It is generally recommended to di-lute the vial in 1 to 2.5 ml.3,28The dispersionarea is usually 1 to 1.5 cm, so this is the recom-mended spacing between injections.3 An injec-tion of 10 U of Botox in the frontalis may resultin relaxation 3 cm from the injection site.20

Saturation of an area with the toxin producesthe clinical results.19,29

Hyperkinetic facial expression lines aremore easily perceived in the upper third of theface, whereas surgical treatments are invasive30

and give inconsistent results.10,19,26 For this rea-son, the upper third of the face has often beenthe target of treatment with botulinum toxintype A. A number of scientific works have re-ported that botulinum treatment is greatly suc-cessful in smoothing hyperkinetic facial linesin the upper face.11,22,24 Recommended doses at

this level vary from 2.5 to 9 U for each muscle.31

Although the dose may need to be individual-ized, a typical dose for the glabella region is 20U, with 8 U at each corrugator muscle and 4 Uin the procerus.13,24

The major muscles involved in hyperkinetic

wrinkles of the neck and the mid and lowerthirds of the face have very specific functions,sometimes working as agonists, sometimes asantagonists, and almost always as fixatives andsynergists in a complex manner, which directlyinfluences the functioning of this facial area.21

Furthermore, the superficial facial muscles in-terdigitate with the superficial portion of themusculoaponeurotic system.21,27,32 Thus, thisregion is complex and requires a rigorous eval-uation to be performed by the physician, with aprecise diagnosis and technique of botulinum

application.Procedures for the lower third of the face

generally involve the muscles surrounding themouth. These muscles function in mastication,deglutition, and articulation of sounds. Theyalso function in facial expressions, includingthe smile, the beak, and the frown. It is im-portant to note that the set of muscles respon-sible for elevating the upper lip and for smilingare also responsible for movements that favorthe formation of nasogenial furrows in the ini-tial phase, before there is skin ptosis or a sig-

nificant increase in malar fat.In addition to closing the mouth, the orbic-

ularis oris is responsible for sunbeam-likewrinkles around the lips. The depressor angulioris pulls the angle of the mouth down and, inconjunction with the depressor labii inferioris,is responsible for the formation of Chinesemoustache or puppet strings in the initialphase before the ptosis of associated skin. Thementalis muscle may account for the half-moonshaped transverse line on the chin.

The platysma muscle contributes to senes-

cent changes in the neck. This muscle origi-nates from the superficial fascia of the upperchest and continues superolaterally to join thesuperficial musculoaponeurotic system. Theposterior fibers of the platysma interdigitatewith the inferior muscles of facial expression,including the depressor anguli oris, mentalis,risorius, and orbicularis oris. During aging, cer-vical skin loses its elasticity, submental fat accu-mulates, and the anterior portion of theplatysma muscle separates to become two di-verging vertical bands. These platysma bands

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often tighten and become more visible whenthe neck is animated.

The objectives of this study were to evaluatethe aesthetic treatment of the face with botuli-num toxin type A in patients without lower faceand neck involvement, to compare the proce-

dures and results in these groups of patients,and to evaluate patients satisfaction with bot-ulinum toxin type A treatment in each of thetreated areas.

METHODS

Design

This was a cohort historical study (individu-al/observational/longitudinal and retrospec-tive study). A total of 100 patients were chosenamong those treated with botulinum toxin type

A, Botox, between July 1996 and July 2000.Patients selected for the study were required tobe more than 20 years old, with treatable wrin-kles and expression lines, and no importantflaccidity or photoaging. The patients hadsought treatment for their hyperkinetic facialwrinkles and did not have any contraindicationto botulinum treatment. To be included in theanalysis, patients were required to have theirfirst follow-up visit at least 10 days and at most15 days after the procedure. Patients were re-quired to have a minimal follow-up time of 6months after the last procedure. Of the 100cases, nine did not meet the requirement thatthe first follow-up visit be between 10 to 15 daysafter the botulinum toxin type A treatment.Thus, there were 91 patients in the sample.

Investigational Protocol

The function of facial and neck muscles as-sociated with hyperkinetic wrinkles was evalu-ated in patient examinations, resulting in theclinical diagnosis and consequent indicationfor treatment. Dynamic films were made thatrecorded the regions to be treated at rest andin motion.13

The procedure was performed by using Bo-tox diluted with 2 ml of saline solution withoutpreservatives for each 100 U of the active prod-uct. Botulinum toxin type A was injected intra-muscularly by using 30 G 12 needles 13 3 mmin the face and 30 G 14 needles 0.3 6 mm inthe neck.31,33,34 The procedures were per-formed with patients sitting,9 without use oftopical anesthetics,26 and after alcohol asepsis9

of the areas to be treated.The median total toxin dose used per pro-

cedure was 100 U. At the level of the mouthand neck, we applied at least 8 U dispersedamong four sites in the orbicularis oris, 4 U atone site in each risorius muscle, and 20 Udivided among 10 sites in the platysma muscle(for the treatment of horizontal neck lines

only).16,35At least 10 and less than 15 days afterthe procedure, patients were reevaluated forimmediate results,14,27 and new films weremade. On this occasion, the investigator veri-fied the treatment results.

Patient satisfaction level36with the treatmentwas evaluated by using a questionnaire (Fig. 1)given in January or February of 2001. A secondinvestigator, who had not performed the pro-cedures, administered the questionnaire. Theobjective of the questions was to get each pa-tients opinion about the results of the treat-

ment during its effective period.

Analysis

For data analysis, patients were subdividedinto two groups on the basis of whether theyhad been treated in the lower face or neck.Group 1 consisted of 56 patients who weretreated only in the upper face and did notreceive treatment in the mouth and neck areas,and group 2 consisted of 35 patients who weretreated in the mouth or neck areas at leastonce during the period of follow-up.

Dichotomous variables were analyzed by us-ing Pearsons chi-square test or Fishers exacttest as appropriate. Continuous variables weresummarized by using means, standard devia-tions, and medians. Medians are presentedwhen the results did not seem to have a sym-metric distribution.37 Differences betweengroups based on ranked scores were analyzedwith Kruskal-Wallis tests or by Mann-Whitney Utests.38 The interaction between variables wasanalyzed using Spearmans correlation coeffi-cient.38 The correlation was considered satisfac-

tory when rho 0.40, and good when rho 0.70.

RESULTS

Patients

The 91 patients in the study ranged in agefrom 20 to 74 years. There were 56 patients ingroup 1, who were treated only in the upperface. These patients had a mean age of 46years. In group 2, 35 patients were treated withbotulinum toxin type A at least once in the



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areas of the mouth and neck. These patientsalso had a mean age of 46 years.

Treatment

Most patients in each of the groups [46 of 56(82.1 percent) in group 1 and 27 of 35 (77.1

percent) in group 2] had just one botulinumadministration during the period of study;there were no differences between groups inthe number of procedures per patient (TableI). The number of procedures per patientranged from one to eight in group 1 and fromone to 11 in group 2. For patients who hadmore than one procedure, the elapsed timebetween procedures ranged from 0.9 to 18months (median, 6.5 months) in group 1 andfrom 2 to 15 months (median, 5.2 months) ingroup 2 (p 0.664). The distribution of the

patients in the two groups had, as a criterion,the treated areas, not the time of the treat-ment, so in both groups, there are patientstreated at the beginning and the end of thestudy distributed symmetrically. Although themedian total dose of botulinum toxin type Aused per procedure was 100 U in both group 1and group 2, the total dose used per procedurewas significantly higher in patients whose treat-ment included the mouth and neck areas (p0.007, Mann-Whitney U test) (Table I).

The injection sites included the mouth (or-

bicularis oris muscle), neck (platysma muscle),forehead (frontal muscle), glabella (procerusand corrugator muscles), eyes (orbicularis oc-uli muscle), nose (nasal portion of the upperlip elevator and nasalis), and nasogenial furrow(risorius or zygomaticus major). The numberof sites injected per procedure was significantlyhigher in patients in group 2 than in group 1(p 0.001, Mann-Whitney U test) (Table I).Follow-ups with periodic reevaluations contin-ued for most patients in each group for at leasta year after the last procedure (Table I). Onaverage, 2.1 sites were injected per procedurein group 1 compared with 5.7 sites injected perprocedure in group 2 (Table II).

Of the 35 patients in group 2 who had pro-cedures at the mouth or neck, 29 (82.9 per-cent) underwent a single procedure that in-cluded the mouth and neck areas. Of the 60procedures performed on patients in group 2,46 included the mouth and neck region (TableII).

Of the 80 procedures performed on patientsin group 1, the majority (78 of 80, 97.5 per-cent) included application of botulinum toxin

FIG. 1. Questionnaire.



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type A for horizontal forehead lines. Othersites frequently targeted were the eyes (in 75 of

80 procedures, 93.8 percent) and the glabella(in 55 of 80 procedures, 68.8 percent). Thenose was targeted in 31 of 80 procedures (38.8percent), and the nasogenial furrow was tar-geted in four of 80 procedures (5.0 percent).

Procedures on patients in group 2 almostinvariably included injections for cosmetic en-hancement of the upper face. Horizontal fore-head lines were treated in 59 of the 60 proce-dures performed on these patients (98.3percent). The eyes and glabella were targeted

in 58 of the 60 procedures (96.7 percent). Thenose was targeted in 37 of 60 procedures (61.7

percent), and the nasogenial furrow was tar-geted in 14 of 60 procedures (23.3 percent).Patients in group 2 were significantly morelikely than patients in group 1 to be treated atthe nose and nasogenial furrow (p 0.007,chi-square tests). Combination therapy (biostimulation by intradermotherapy-meso-therapy or fillers used along with botulinumtoxin type A) was more common in patientswith treatment sites at the mouth and neckthan in patients with treatment confined to the

TABLE IIFrequency Distribution of the Total Number of

Procedures and the Number of Procedures Performed at

the Mouth and Neck Areas in Patients in Group 2

Total No. ofProcedures No. of Patients

No. ofProcedures at theMouth and Neck No. of Patients

1 27 (77.1%) 1 29 (82.9%)2 2 (5.7%) 2 3 (8.6%)3 3 (8.6%) 3 2 (5.7%)4 1 (2.9%) 4 0 (0%)5 1 (2.9%) 5 1 (2.9%)

11 1 (2.9%)

TABLE III

Number of Patients with Procedures Performed in

Combination with Botulinum Toxin A Treatment*

ProcedureGroup 1,(n 56)

Group 2,(n 35)

Biostimulation by intradermotherapy 1 (1.8%) 8 (22.9%)Fillers 3 (5.4%) 6 (17.1%)Biostimulation by intradermotherapy fillers 1 (1.8%) 7 (20.0%)

None 51 (91.1%) 14 (40.0%)

* Patients in group 2 were significantly more likely than those in group 1to have combination therapy (p 0.001).

TABLE I

Distribution of the Patients by Age, Sex, Number of Procedures, Total Doses per Procedure, Number of Sites Injected per

Procedure, Follow-Up Period after the last Procedure, and Diagnosis

Group 1 Group 2 p Value

Age

Mean SD 46 10.2 47 9.8Range 2074 2565

Sex, n (%)Male 6 (11) 2 (6)Female 50 (89) 33 (94)

Number of procedures 0.515Mean SD 1.4 1.2 1.7 1.9Median 1 1Range 18 111

Total dose per procedure (U) 0.007Mean SD 85 21 95 14Median 100 100Range 20100 50100

Number of sites injected per procedure 0.001Mean SD 3.1 0.87 5.7 1.0Median 3 6

Range 15 37Follow-up period after the last procedure (mo) 0.337Mean 25 21Median 17.5 13Range 1249 749

Diagnosis, n (%) 0.001Expression lines only 56 (100%) 16 (45.7%)Expression lines and furrows 0 14 (40.0%)Expression lines and flaccidity 0 2 (5.7%)Expression lines and acne scarring 0 1 (2.9%)Expression lines, flaccidity, and localized fat 0 1 (2.9%)Expression lines and melanosis 0 1 (2.9%)



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mid and upper face (p 0.001, chi-square test)(Table III).

Success Rate

At the first reevaluation of patients after bot-ulinum toxin type A application, unsatisfactory

results were noted in only two of 35 patients(5.8 percent) of group 2. One patient had adiscrete eyebrow asymmetry, noted by the in-vestigator but not by the patient, which waslikely caused by inappropriate targeting of thebotulinum. A second patient had insufficientsmoothing of the expression lines consideredby the investigator to be have resulted from aninsufficient dose of botulinum, although 100 Uhad been given to this patient. Results from theother 33 patients in group 2 and all 56 patientsin group 1 met the investigators expectations

and were considered satisfactory. Others com-plications such as sensation of loss of strengthand local infection did not occur in eithergroup.

Patient Satisfaction and Impressions

A total of 20 of the 56 patients (35.7 percent)in group 1 and 20 of the 35 patients (57 per-cent) in group 2 answered the questionnaire.These will be called group 1 responders andgroup 2 responders. Both of the patients withunsatisfactory results at the first follow-up visit

were group 2 responders. All of the patientswho responded to the questionnaire werewomen, and the mean age was 46.7 years forgroup 1 responders and 46.0 years for group 2responders. The treatment characteristics ofthe subsets of patients who responded to thequestionnaire seemed to reflect those of theentire study population. The mean total doseof botulinum toxin type A administered perprocedure was slightly higher in group 2 re-sponders (95 U) than in group 1 responders(85 U), and the dose was divided among sig-nificantly more sites (average of 3.1 sites ingroup 1 responders and 5.9 sites in group 2responders, p 0.001, Mann-Whitney U test).

Among the patients who responded to thequestionnaire, 18 of 20 group 1 responders (90percent) and 16 of 20 group 2 responders (80percent) had a single procedure during thestudy. The average number of procedures per-formed on patients (1.2 for group 1 respond-ers and 1.8 for group 2 responders) was similarbetween groups (p 0.338, Mann-Whitney Utest). The patients who responded to the ques-tionnaire showed a distribution of treatment

sites similar to those in the entire study popu-lation. As for the entire study population,group 2 responders were significantly morelikely than group 1 responders to have combi-nation therapy using botulinum (p 0.012,chi-square test).

In response to the 12 questions posed in thequestionnaire, group 1 responders and group2 responders generally gave similar answers.Almost all patients [18 of 20 group 1 respond-ers (90 percent) and 20 of 20 group 2 respond-ers (100 percent)] were satisfied or very satis-fied with their Botox cosmetic treatment. Thecost-effectiveness of the treatment was rated asgood or very good by 16 of 20 group 1 respond-ers (80 percent) and 17 of 20 group 2 respond-ers (85 percent). Many patients in each groupfailed to accurately list the sites that had been

treated, even though they had received an ex-planation about the technical terms in thequestionnaire. However, in both groups, theforehead was singled out most frequently asthe site in which the results were more exuber-ant. The results were most pronounced at theforehead or forehead and eyes for 70 percentof group 1 responders and 60 percent of group2 responders. Interestingly, 75 percent of thegroup 2 responders did not mention themouth or neck as a site with more exuberantresults. However, most of the group 2 respond-

ers did notice results in these areas. Amonggroup 2 responders, 50 percent reported thatresults were noticed in all treated sites; onlytwo patients (10 percent) reported not notic-ing results at the neck, whereas three patients(15 percent) reported not noticing results atthe mouth.

Most patients (100 percent of group 1 re-sponders and 85 percent of group 2 respond-ers) began to see results within 10 days of theprocedure. Three group 2 responders (15 per-cent) responded that the results were first evi-dent after 10 days. Notably, 75 percent ofgroup 1 responders and 80 percent of group 2responders reported the consolidation of re-sults within 15 days of the procedure. Although20 percent of group 1 responders reportedthat the results were maintained for less than 3months, the results were maintained for 3 to 4months in 45 percent of group 1 respondersand for 6 months or more in 35 percent ofgroup 1 responders. By comparison, amonggroup 2 responders, the results were main-tained for less than 3 months in 5 percent ofpatients, for 3 to 4 months in 60 percent of



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patients, for 5 months in 20 percent of pa-tients, and for 6 months or more in 15 percentof patients.

With respect to their skin, 45 percent ofgroup 1 responders believed that it improvedafter the treatment, 50 percent reported no

change, and 5 percent believed that it wors-ened. Improvement in the skin was much moreprevalent in group 2 responders; 85 percent ofgroup 2 responders reported that the skin im-proved after botulinum treatment, whereas theremaining 15 percent of patients reported nochange (p 0.059 between groups). Improve-ment in the skin was characterized by morebrightness and lushness.

In response to the question asking whetherother people had noticed a difference in themafter the treatment, 75 percent of group 1

responders and 95 percent of group 2 respond-ers reported that others had noted an improve-ment. Many of the compliments received per-tained to the natural appearance of rejuvenationprovided by the treatment.

The questionnaire was given at least 6months after the last procedure. Most of thepatients in each group (70 percent of group 1responders and 90 percent of group 2 respond-ers) reported that they would be willing toundergo another botulinum procedure; 40percent of group 1 responders and 30 percent

of group 2 responders had already repeatedthe second procedure.No significant correlations were found be-

tween the dose and the time of onset or theduration of the results in either group, becausealmost all of the patients received high dosesaround 100 U. Likewise, the satisfaction levelof patients was not significantly correlated withthe time of onset or the duration of results, theapplication site, the number of sites injected,or the number of procedures, although an ap-parent tendency was noted in group 2.

DISCUSSION

This was a retrospective study evaluatingevents that occurred before the survey. Patientswere treated with the objective of meeting alltheir needs concerning dynamic facial wrin-kles, not only those at the mouth and necklevel, although our main goal was the analysisof results in these two specific areas. The re-sults showed that botulinum toxin type A treat-ment for patients who had procedures at themouth and neck level was at least as successful

as that for patients who had procedures for theupper face only.

We chose to survey charts from 100 patientsbecause we believed that this sample size couldbe large enough to provide adequate power forstatistical analyses. Because this was a retrospec-

tive study, the inclusion and exclusion criteriafor treatment reflected the indications for bot-ulinum toxin type A cosmetic procedures. Theonly additional inclusion criteria for analysiswere related to the follow-up of patients be-cause we were interested in evaluating the re-sults over time.

Our injection procedure was standardizedand consistent with reported procedures. Wechose to dilute each 100-U Botox vial with 2 mlof saline solution without preservatives. We be-lieve that this is the ideal dilution for cosmetic

procedures because the volume is largeenough to allow rigid control of the dose (1U/0.02 ml) and small enough to avoid unde-sired diffusion of botulinum toxin type A tomuscles other than those targeted fortreatment.

The doses used in the mouth and neck re-gions were compatible with those recom-mended in the literature. However, the aver-age total dose per procedure for patients ineach group was higher than the typical totaldose described in the literature. Because of our

backgrounds and experience, we know muscleswell and worked for many years with neuro-logic patients for whom botulinum toxin typeA doses are often higher than those initiallyrecommended in cosmetics. Therefore, usingrelatively high doses did not trouble us. Ourprevious education and experience gave usconfidence to use these doses, but we werecareful to maintain a minimum time intervalbetween procedures of at least 3 months tominimize the risk of antibody formation.

We must emphasize that the doses referred toin this article pertain only to procedures per-formed with Botox. We are aware that otherpreparations of botulinum toxin type A andother serotypes have different potencies, andtherefore, doses cannot be extrapolated betweendifferent botulinum toxin products.7,39

The clinical diagnosis is extremely importantin obtaining satisfactory results with botulinumtoxin type A treatment. Wrinkles have severalcauses, including gravity, loss of elasticity dur-ing aging, crushing of the skin by the pillowduring sleep, and muscle hyperactivity. Onlyhyperkinetic lines resulting from muscle activ-



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ity are amenable to botulinum toxin type Atreatment; botulinum therapy produces excel-lent results in smoothing these lines.4,4042

Most of the patients in the sample werewomen. This may be because women are gen-erally more concerned about aesthetics than

men. Nonetheless, we have observed a substan-tial increase in the demand for this kind oftreatment by men. The ages of patients in thesample varied widely, from 20 to 74 years. Thisshows that a concern about appearance is notrelated to the fact of being young or old, but itmay be influenced by cultural attitudes. In theliterature, the most exuberant results havebeen reported in people in their 30s to 50s,40

particularly in women.13 As our specific inten-tion was to evaluate the results of treatment ofthe mouth and neck areas, we divided the sam-

ple into two groups: those receiving at least onetreatment in these areas and those who werenever treated at the mouth and neck level. Thegroups were homogeneous with respect to ageand sex.

From the beginning of our work in the aes-thetics area, patient evaluations before the pro-cedures were standardized. Hyperkinetic ex-pression wrinkles are caused by movement,and we treat them by relaxing the muscles thatare involved; therefore, static records do notseem appropriate, and we believe that filming

is the ideal manner to record images. In thecourse of our practice, routine procedures forfunctional evaluation of muscles and for film-ing patients had already been established, andthese procedures were used for our aestheticspatients.

The first evaluation after the procedure was10 to 15 days later. This seems to be an idealtime for follow-up evaluation because the re-sults were usually consolidated within 15 days.Patients total follow-up time was quite long,approximately 2 years on average. This timewas sufficient for us to evaluate possible long-term complications and for both patients andphysicians to settle their initial impressionsabout the results.

In the analysis of the results, patients weredivided into two groups on the basis of whethertheir botulinum toxin type A procedure tar-geted the mouth and neck areas. Patients inthe two groups were similar with respect to ageand sex. However, patients who were treated inthe areas of the mouth and neck (group 2)were also treated, when necessary, in otherfacial areas to reach results compatible with

their expectations. The forehead and eyes werefrequently targeted in these patients, and thenasogenial furrow and nose were significantlymore likely to be targeted in these patientsthan in patients whose procedures did not in-clude the mouth or neck (group 1). Thus, in

group 2, the number of sites injected in asingle procedure was significantly greater thanin group 1, and the average total toxin dosewas also higher than in group 1. The totalfollow-up time of patients, the number of pro-cedures performed per patient within the totalfollow-up time, the number of repetitions of aprocedure in the same patient within the totalfollow-up time, and the time interval betweenprocedures in individual patients did not differbetween the groups.

It is notable that 10 patients (18 percent) in

group 1 and 8 in group 2 (23 percent) spon-taneously repeated the procedure within theperiod surveyed, with a median interval be-tween procedures of 6.5 months for patients ingroup 1 and 5.2 months for patients in group2. We should emphasize here that the patientswere all from high social classes, and we believethat they would not delay in repeating theprocedure for monetary reasons. In addition,these patients were adamant in their desire foran enhanced cosmetic appearance, suggestingto us that this time interval corresponds, in

fact, to the interval for maintenance of results.This duration of results is longer than the du-ration of results that has typically been de-scribed in the literature (3 to 4 months).43

The results of 140 procedures performed in91 patients were analyzed in this study. Ofthese procedures, 46 included the regions ofthe mouth and neck in 35 patients. Many of theprocedures were combined with mesotherapyor soft-tissue augmentation, as has been de-scribed in the literature.13,26,40,44 Botulinumtoxin type A treatment was significantly morelikely to be used adjunctively with other ther-apy in patients in group 2. This may have oc-curred because some patients in this group haddiagnoses that were more complicated thanexpression lines and because furrows and pro-cedures in the area of the mouth may espe-cially benefit from combination therapy.

Despite the great number of procedures per-formed and assessed, we noted only two pa-tients (1.4 percent) with unsatisfactory results,including an adverse event (brow asymmetry)that was not serious and a lack of adequateeffect. Most studies have reported a higher



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incidence of complications.22,23,45,46 Asymme-tries and ptosis are the most frequent compli-cations46; however, some authors do not con-sider slight asymmetries as complications orfailures in the results.47

A total of 20 patients in each group re-

sponded to the questionnaire that was admin-istered. The groups of patients who respondedto the survey were also similar with respect toage and sex. Patients in both groups reported ahigh level of satisfaction with the procedure.The forehead region was mentioned by 90 per-cent of patients in both groups as the regionwith the most exuberant results.

The literature suggests that results may bebetter sustained after repeated injections ofbotulinum toxin type A15; however, we couldnot establish this correlation in our study be-

cause most patients had a single procedureduring the period under study. Nonetheless,most patients responded that the duration ofeffect was at least 3 months, and the durationof effect was 6 months or more in 25 percent ofthe patients who responded to the question-naire. This duration of effect compares favor-ably with that reported in the literature.

In general comments, some patients com-plained that the duration of the results was tooshort. This complaint is also referred to in theliterature.4 Several patients also reported dis-

satisfaction with cost-effectiveness, althoughmost of them would repeat the procedure.One of the patients commented on the powerof the toxin to prevent the emergence of newwrinkles. This is also referred to in the litera-ture as one of the advantages of botulinumtoxin type A treatment.40 Some patients statedthat they were especially pleased with the re-sults when they considered their ages. Skinchanges that occur during aging include a lossof elasticity and consequent flaccidity. Becausebotulinum promotes a chemical lifting28,40 ofsome regions treated, it promotes a youngerappearance beyond its effect in clearing wrin-kles. An example of this is the arching of eye-brows possible with botulinum, which pro-motes a younger appearance.28,30,48 On theother hand, under the same conditions of skinflaccidity, inappropriate injections of botuli-num can result in complications such as ptosisthat mimic the appearance of aging.22

It was not possible to establish a correlationbetween the dose given and the time of onsetor the duration of the results, probably becausethe doses given were consistently high. Also,

because almost all patients were satisfied withthe procedure, it was not possible to establish astatistical relationship between the satisfactionlevel of patients and other parameters such asthe sites of application, the number of applica-tions, or even the duration of the results.

CONCLUSIONS

Excellent results were obtained for patientstreated with botulinum toxin type A for cos-metic purposes. In using botulinum for aes-thetic indications in the face, functional evalu-ation of the facial muscles is essential for anappropriate diagnosis, and knowledge of thetopographic and functional anatomy is essen-tial to avoid the most frequent complications ofthe procedures. Our retrospective analysisdemonstrated that when we treat the face as a

whole, including the mouth and neck, thedoses used in the procedure tend to be higher,and the number of injected sites tends to begreater.

The satisfaction level of patients treated withbotulinum was high, for both patients withtreatment of only the upper face and patientswith treatment of the mouth and neck areas.Improvement of skin vitality was reported moreoften by patients who received extensive treat-ment with botulinum toxin type A, includingtreatment of the mouth and neck areas. Patient

complaints about the procedures were limitedto the cost of the procedures and the durationof the effects, which typically diminishedwithin 6 months.

M. Matilde de M. Spsito, M.D., Ph.D.R. Deputado Larcio Corte, 1200 apt. 81APanambyMorumbiSo Paulo, SP Brazil [email protected]

REFERENCES

1. Carruthers, A., and Carruthers, J. History of the cos-metic use of botulinum A exotoxin. Dermatol. Surg. 24:

1168, 1998.2. Markey, A. C. Botulinum A exotoxin in cosmetic der-

matology. Clin. Exp. Dermatol. 25: 173, 2000.3. Benedetto, A. V. The cosmetic uses of botulinum toxin

type A. Int. J. Dermatol. 38: 641, 1999.4. Binder, W. J., Blitzer, A., and Brin, M. F. Treatment of

hyperfunctional lines of the face with botulinum toxinA. Dermatol. Surg. 24: 1198, 1998.

5. Carruthers, A., Lowe, N. J., and Menter, M. A. A multi-center, double-blind, randomized, placebo-controlled,parallel study of the safety and efficacy of botulinumtoxin type A (Botox) in subjects with glabellar lines. InProceedings of the AAD, San Francisco, 2000.

6. Woodruff, B. A., Griffin, P. M., McCroskey, L. M., et al.Clinical and laboratory comparison of botulism from



11/11

toxin type A, B, andE in theUnited States, 19751988.J. Infect. Dis. 166: 1281, 1992.

7. Lowe, N. J. Botulinum toxin type A for facial rejuvena-tion: United States and United Kingdom perspectives.

Dermatol. Surg. 24: 1216, 1998.8. Blitzer, A., Brin, M. F., Keen, M. S., and Aviv, J. E. Bot-

ulinum toxin for the treatment of hyperfunctional

lines of the face. Arch. Otolaryngol. Head Neck Surg. 119:1018, 1993.9. Carruthers, A., Kiene, K., and Carruthers, J. Botulinum

A exotoxin use in clinical dermatology. J. Am. Acad.Dermatol. 34: 788, 1996.

10. Guerrissi, J. O. Intraoperative injection of botulinumtoxin A into orbicularis oculi muscle for the treatmentof crows feet. Plast. Reconstr. Surg. 105: 2219, 2000.

11. Garcia, A.,and Fulton, J. E., Jr. Cosmetic denervation ofthe muscles of facial expression with botulinum toxin:A dose response study. Dermatol. Surg. 22: 39, 1996.

12. Klein, A. W. Dilution and storage of botulinum toxin.Dermatol. Surg. 24: 1179, 1998.

13. Pribitkin, E. A., Greco, T. M., Goode, R. L., and Keane,W. M. Patient selection in the treatment of glabellar

wrinkles with botulinum toxin type A injection. Arch.Otolaryngol. Head Neck Surg. 123: 321, 1997.

14. Fulton, J. E. Botulinum toxin: The Newport Beach ex-perience. Dermatol. Surg. 24: 1219, 1998.

15. Ahn, M. S., Catten, M., and Maas, C. S. Temporal browlift using botulinum toxin A. Plast. Reconstr. Surg. 105:1129, 2000.

16. Matarasso, A., Matarasso, S. L., Brandt, F. S., and Bell-man, B. Botulinum A exotoxin for the managementof platysma bands. Plast. Reconstr. Surg. 103: 645, 1999.

17. Stratigos, A. J., Arndt, K. A., and Dover, J. S. Advancesin cutaneous aesthetic surgery. J.A.M.A. 280: 1397,1998.

18. Oliveira, M. V., and Oliveira, A. P. Toxina botulnica notratamento de rugas faciais. Available at: http://ww-w.cosmedical.com.br/botox.htm. Accessed April,2000.

19. Carruthers, J. D., and Carruthers, J. A. Treatment ofglabellar frown lines with C. botulinumA exotoxin.

J. Dermatol. Surg. Oncol. 18: 17, 1992.20. Klein, A. W., Wexler, P., Carruthers, A., and Carruthers,

J. Treatment of facial furrows and rhytides. Dermatol.Clin. 15: 595, 1997.

21. Borodic, G. E. Botulinum A toxin for (expressionistic)ptosis overcorrection after frontalis sling. Ophthalmol.Plast. Reconstr. Surg. 8: 137, 1992.

22. Keen, M., Blitzer, A., Aviv, J., et al. Botulinum toxin Afor hyperkinetic facial lines: Results of double-blind,placebo controlled study. Plast. Reconstr. Surg. 94: 94,

1994.23. Song, K. H. Botulinum toxin type A injections for thetreatment of frown lines. Ann. Pharmacother. 32: 1365,1998.

24. Hankins, C. L., Strimling, R., and Rogers, G. S. Botu-linum toxin for glabellar wrinkles: Dose and response.

Dermatol. Surg. 24: 1181, 1998.25. Brenner, R., Madhusoodanan, S., Korn, Z., and Spitzer,

M. Acute anxiety and depression induced by loss ofsensation and muscle control after botulinum toxin Ainjection (Letter). South. Med. J. 92: 738, 1999.

26. Fagien, S. Botox for the treatment of dynamic and hy-perkinetic facial lines and furrows: Adjunctive use infacial aesthetic surgery. Plast. Reconstr. Surg. 103: 701,1999.

27. Brandt, F. S., and Bellman, B. Cosmetic use of botuli-num A exotoxin for the aging neck. Dermatol. Surg. 24:1232, 1998.

28. Huang, W., Rogachefsky, A. S., and Foster, J. A. Browliftwith botulinum toxin. Dermatol. Surg. 26: 55, 2000.

29. Borodic, G. E.,Pearce, L. B., Smith, K. L., Phelan, M.,andFerrante, R. Botulinum B toxin as an alternative to

botulinum A toxin: A histologic study. Ophthalmol.Plast. Reconstr. Surg. 9: 182, 1993.

30. Castaares, S. Forehead wrinkles, glabellar frown andptosis of the eyebrows. Plast. Reconstr. Surg. 34: 406,1964.

31. Edelstein, C., Shorr, N., Jacobs, J., Balch, K., and Gold-berg, R. Oculoplastic experience with the cosmeticuse of botulinum A exotoxin. Dermatol. Surg. 24: 1208,1998.

32. Wieder, J. N., andMoy, R. L. Understanding botulinumtoxin: Surgical anatomy of the frown, forehead, andperiocular region. Dermatol. Surg. 24: 1172, 1998.

33. Fields, K. A. Skin breakthroughs in the year 2000. Int.J. Fertil. Womens Med. 45: 175, 2000.

34. West, T. B., and Alster, T. S. Effect of botulinum toxintype A on movement-associated rhytides followingCO2 laser resurfacing. Dermatol. Surg. 25: 259, 1999.

35. Carruthers, A., and Carruthers, J. Clinical indicationsand injections technique for the cosmetic use of bot-ulinum A exotoxin. Dermatol. Surg. 24: 1189, 1998.

36. Olver, J. M. Botulinum toxin A treatment of overactivecorrugator supercilii in thyroid eye disease. Br. J. Oph-thalmol. 82: 528, 1998.

37. Levin, J. Estatstica aplicada a cincias humanas, 2nd Ed.So Paulo: Editora Harbra, 1987.

38. Siegael, J. Estatstica no-paramtrica, 1st Ed: So Paulo:Editora McGraw Hill do Brasil, 1981.

39. Goodman, G. Botulinum toxin for the correction ofhyperkinetic facial lines. Australas. J. Dermatol. 39: 158,1998.

40. Foster, J. A., Wulc, A. E., and Holck, D. E. Cosmeticindications for botulinum A toxin. Semin. Ophthalmol.13: 142, 1998.

41. Lowe, N. J., and Wirder, J. M. Botulinum toxin for hy-perkinetic facial lines: A placebo controlled study.Cosm. Dermatol. 8: 16, 1998.

42. Niamtu, J., III. Aesthetic uses of botulinum toxin A.J. Oral Maxillofac. Surg. 57: 1228, 1999.

43. Ahn, H. Y., Park, M. Y., Park, D. H., and Han, G. G.Botulinum toxin A for the treatment of facial hyperki-netic wrinkle lines in Koreans. Plast. Reconstr. Surg.105: 778, 2000.

44. Carruthers, J., and Carruthers, A. The adjunctive usageof botulinum toxin. Dermatol. Surg. 24: 1244, 1998.

45. Lowe, N. J., Maxwell, A., and Harper, H. Botulinum Aexotoxin for glabellar folds: A double-blind, placebo-controlled, study with an electromyographic injectiontechnique. J. Am. Acad. Dermatol. 35: 569, 1996.

46. Matarasso, S. L. Complications of botulinum A exo-toxin for hyperfunctional lines. Dermatol. Surg. 24:1249, 1998.

47. Matsudo, P. K. R. Botulinum toxin for correction offronto-glabella wrinkles: Preliminary evaluation. Aes-thetic Plast. Surg. 20: 439, 1996.

48. Huilgol, S. C., Carruthers, A.,and Carruthers, J. D. Rais-ing eyebrows with botulinum toxin. Dermatol. Surg. 25:373, 1999.


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