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Botulinum Toxin A Treatment for Primary Hemifacial Spasm
A 10-Year Multicenter Study
Giovanni Defazio, MD;
Giovanni Abbruzzese, MD;
Paolo Girlanda, MD;
Laura Vacca, MD;
Antonio Currà, MD;
Roberto De Salvia, MD;
Roberta Marchese, MD;
Roberto Raineri, MD;
Francesco Roselli, MD;
Paolo Livrea, MD;
Alfredo Berardelli, MD
Arch Neurol. 2002;59:418-420.
ABSTRACT
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Background Botulinum toxin A (BTX) is the currently preferred symptomatic treatment
for primary hemifacial spasm (HFS), but its long-term efficacy and safety
are not known.
Objective To assess the long-term effectiveness and safety of BTX in the treatment
of primary HFS.
Design Retrospective review of medical records of the 1st and 10th years of
treatment.
Setting Outpatient clinics of 4 Italian university centers in the Italian Movement
Disorders Study Group.
Participants A series of 65 patients with primary HFS who had received BTX injections
regularly for at least 10 years.
Main Outcome Measures Mean duration of improvement and quality of the effect induced by the
preceding treatment (measured using a patient self-evaluation scale) and occurrence
and duration of adverse effects in the 1st and 10th years of treatment.
Results Using a mean BTX dose per treatment session similar to that used by
others, we obtained a 95% response rate and an overall mean duration of improvement
of 12.6 weeks during year 1. The effectiveness of BTX in relieving the symptoms
of primary HFS, as measured by the response rate and average duration of improvement,
remained unchanged in the 1st and 10th years. Patients needed statistically
similar BTX doses in the 1st and 10th years. The rate of local adverse effects
(including upper lid ptosis, facial weakness, and diplopia) diminished significantly
in the 10th year of treatment.
Conclusion Treatment with BTX effectively induces sustained relief from symptoms
of HFS in the long term, with only minimal and transient adverse reactions.
INTRODUCTION
BOTULINUM TOXIN A (BTX) is the currently preferred symptomatic treatment
for primary hemifacial spasm (HFS).1-6
Because HFS rarely remits spontaneously,7 most
patients need to continue treatment for many years, if not throughout life.
The long-term efficacy and safety of BTX is therefore an increasingly important
question. Few of the numerous published studies2, 5-9
assessing BTX treatment of HFS included patients with serial treatments covering
several years, and none had follow-up of more than 5 years. In this multicenter
study, we reviewed the long-term effectiveness and safety of BTX treatment
in a series of 65 patients with primary HFS who had received BTX injections
regularly for at least 10 years.
PATIENTS AND METHODS
Patients with primary HFS attending the outpatient clinics at 4 Italian
university centers ("La Sapienza" Rome, Bari, Genova, and Messina) belonging
to the Italian Movement Disorders Study Group were enrolled in this retrospective
study. All centers used standard methods for recording information, injecting
BTX, and assessing treatment effectivness.10
A total of 86 patients (28 men and 58 women) received a diagnosis of primary
HFS according to published criteria11 and began
treatment with BTX between January 1, 1987, and January 1, 1990. Their mean
± SD age at first symptoms was 51.0 ± 11.4 years, and mean age
at first treatment was 58.0 ± 12.0 years. The intensity and frequency
of spasms differed in patients, but all reported marked interference with
activities of daily living (reading, eating, talking, watching television,
and mental concentration), social tasks, or both. Of the total cohort of 86
patients initially available for study, 21 did not attend follow-up visits
for 12 months or more and were thus considered "dropouts." Of the 21 dropouts,
5 had not discontinued BTX therapy but had switched to other treatment centers
closer to their homes. The corrected dropout rate was therefore 19% (16/86).
Reasons for treatment discontinuation included death from other causes (5
patients), unsatisfactory results (6 patients, 2 of whom underwent surgery),
and complete and long-lasting symptom relief (2 patients). Three patients
dropped out for unknown reasons. All patients who dropped out discontinued
treatment during the second or third year.
The remaining 65 patients (19 men and 46 women) completed at least 10
years of BTX treatment with the same commercial product (Botox; Allergan,
Irvine, Calif). Their mean ± SD age at onset of symptoms of HFS was
50.0 ± 11.3 years, and mean age at first treatment was 56.0 ±
11.0 years. During the initial months of treatment, patients were continuously
monitored and treated when spasms reappeared. Thereafter, they returned only
when they needed another injection because symptoms had recurred. Before each
injection session, patients were questioned about the results of the previous
session. To assess the long-term effectiveness and safety of BTX, we reviewed
patients' medical records for the 1st and 10th years of treatment and collected
the following information: date of injections, total dose, number and location
of injection sites, duration of improvement (defined as the interval between
treatment and the recurrence of symptoms severe enough to prompt patients
to receive another injection) and quality of the effect induced by the preceding
treatment, and occurrence and duration of adverse effects. Because of the
lack of reliable clinical methods to assess the severity of HFS, the quality
of the BTX effect was measured using a patient self-evaluation scale. At each
injection visit, changes in the patient's status were scored as no change
(muscle spasms that interfered with activities of daily living or social tasks
in such a way that patients continued to be socially embarrassed), moderate
improvement (reduction in the frequency and duration of spasms so that they
interfered slightly with activities of daily living or social tasks), or marked
improvement (spasms in the injected muscle had ceased altogether so that they
no longer interfered with activities of daily living or social tasks). Patients
who reported no improvement or a short-lasting benefit had their BTX dose
increased according to their individual needs. At each session, BTX (10 U
per 0.1 mL of isotonic sodium chloride solution final concentration) was injected
into 3 or 4 sites in the orbicularis oculi only. We treated HFS by injecting
the orbicularis oculi muscle alone rather than both the orbicularis oculi
and oris muscles because BTX injection into the latter muscle often causes
weakness of the lower facial muscles.4, 6-10
Data were analyzed for statistical significance using the paired t test and the  2 test.
RESULTS
The 65 patients who completed the 10-year course of continuous BTX treatment
received a total of 239 treatments during the first year. On average, each
patient received a cumulative yearly dose of 70 U subdivided in 3 to 4 treatment
sessions. The mean dose of BTX per treatment session was 17.5 U (range, 7.5-45.0
U). According to patients' subjective impressions, nearly all treatments improved
HFS: the response rate was 96%. Although lower face muscles were not directly
injected, most patients reported marked benefit in the orbicularis oris. Treatment
failures mostly concerned the first injection. In later sessions, when the
dose was increased, the symptoms diminished. The mean ± SD duration
of effect was 12.6 ± 5.7 weeks. No significant difference was found
between treatment variables investigated in the 1st and 10th years of treatment,
including number of treatments per patient, number of BTX units per treatment
session, cumulative yearly dose per patient, response rate, and duration of
effect (Table 1).
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Table 1. Comparison of Findings at the Beginning and End of 10 Years
of Botulinum Toxin A Treatment in 65 Patients With Primary Hemifacial Spasm
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Adverse reactions were observed in 24 of 65 patients during the first
year of treatment and in 8 of 65 patients during the 10th year (P = .02). Likewise, the number of treatment sessions associated with
BTX-induced adverse reactions dropped significantly from the 1st to the 10th
year (34 of 239 vs 8 of 232 treatment sessions; P<.001).
The most frequently reported adverse reaction was upper lid ptosis, followed
by weakness of lower facial muscles on the side of injection and diplopia
(Table 2). The reduction from
the 1st to the 10th years was significant for upper lid ptosis but not for
lower facial weakness on the side of injection and diplopia, probably because
of lack of statistical power. Local adverse effects were severe and interfered
with daily activities and social tasks in approximately 30% of cases. The
mean dose of BTX was slightly but not significantly higher for injection sessions
that induced adverse reactions than for sessions that did not (16.4 ±
6.9 U vs 14.2 ± 5.8 U; P = .23).
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Table 2. Comparison of Adverse Events at the Beginning of 10 Years
of Botulinum Toxin A Treatment in 65 Patients With Primary Hemifacial Spasm
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COMMENT
Our multicenter review provided a larger sample of patients with primary
HFS receiving BTX treatment than would be possible with one center alone.
It also had the advantage of 10-year follow-up. Our study provides evidence
of the long-term effectiveness and safety of using BTX to relieve the symptoms
of primary HFS.
Although BTX treatment for HFS began in the early 1980s, most available
studies5-9
describe relatively short treatment courses and follow-up. In these investigations,
although maximum follow-up ranged from 4 to 8 years, few patients received
continuous treatment throughout the study. Elston5
reported the results of a 7-year study without detailing the results of long-term
treatment. In 1995, Van den Bergh et al8 reported
BTX treatment outcome in 40 patients, but they did not provide long-term clinical
effects. Mauriello et al7 reported 47 patients
who had been treated for a median of 4.9 years. Jitpimolmard et al9 conducted a detailed clinical analysis of the effects
produced by BTX use, but mean follow-up was 2.4 years, and only 21 patients
completed approximately 3 years of treatment.
Until the present study of 65 patients treated for 10 years, data were
lacking on longer-term outcome and, most important, on response rate, duration
of improvement, and long-term adverse reactions.5-9
Using a mean BTX dose per treatment session similar to that used by
other researchers,1-4,6-7
we obtained a 95% response rate and an overall mean duration of improvement
of 12.6 weeks during the first year of treatment. This outcome compares well
with shorter-term results.1-4
The effectiveness of BTX treatment in relieving the symptoms of primary HFS,
as measured by the response rate and average duration of improvement, remained
unchanged in the 1st and 10th years. Hence, BTX use seems to induce substantial,
sustained relief over time. Further support for its prolonged efficacy comes
from the statistically similar doses our patients needed in the 1st and 10th
years. Although other researchers reported variable dose reduction during
follow-up, despite an unchanged duration of benefit,5, 8-9
they used a higher initial dose than we did.
Consistent with previous studies,1-9
our patients' most frequent adverse reaction was upper lid ptosis, followed
by weakness of lower facial muscles on the side of injection, probably due
to spread of the toxin from the lower eyelid. The overall rate of BTX-induced
adverse reactions diminished significantly in the 10th year of treatment.
Because the mean number of BTX units per treatment session remained practically
unchanged throughout the study, we attribute the reduction to optimization
of the injection technique.
A potential limitation of our study may be that to rate the quality
of the effect of BTX treatment on HFS we used a patient self-evaluation scale
rather than an observer-based rating. Valid and reliable clinical methods
of assessing the severity of HFS are lacking, however. In addition, no direct
relationship may exist between the intensity and frequency of facial spasms
and interference with activities of daily living or other social tasks. Thus,
a patient self-evaluation scale may express the impact of treatment on HFS
in the long term better than 4- or 5-point severity scales based on an observer's
subjective assessment of eyelid spasms.12
This study provides valuable information regarding the long-term effectiveness
and safety of using BTX to relieve the symptoms of primary HFS. Injection
of BTX into the orbicularis oculi muscle is a safe and effective treatment
for the symptoms of HFS and effectively induces sustained relief from symptoms
in the long term (10 years in this study), with only minimal and transient
adverse reactions.
AUTHOR INFORMATION
Accepted for publication September 24, 2001.
Author contributions: Study
concept and design (Drs Defazio, Abbruzzese, Girlanda, and Berardelli); acquisition of data (Drs De Salvia, Vacca, Marchese, Currà,
Raineri, and Roselli); analysis and interpretation of data (Drs Defazio, Abbruzzese, Girlanda, and Berardelli); drafting of the manuscript (Drs Defazio, Abbruzzese, Girlanda, Vacca,
Marchese, Currà, Raineri, Roselli, and Berardelli); critical revision of the manuscript for important intellectual content
(Drs Defazio, Abbruzzese, Girlanda, Berardelli, Vacca, and Marchese); statistical expertise (Drs Defazio and De Salvia); administrative, technical, and material support (Drs Defazio
and De Salvia); study supervision (Drs Defazio and
Berardelli).
Corresponding author and reprints: Giovanni Defazio, MD, Department
of Neurological and Psychiatric Sciences, University of Bari, Piazza Giulio
Cesare 11, I-70124 Bari, Italy (e-mail: gdefazio{at}neurol.uniba.it).
From the Department of Neurological and Psychiatric Sciences, University
of Bari, Bari (Drs Defazio, De Salvia, Roselli, and Livrea); the Department
of Neurological Sciences and Vision, University of Genova, Genova (Drs Abbruzzese
and Marchese); the Department of Neurosciences, Psychiatric and Anaesthesiological
Sciences, University of Messina, Messina (Drs Girlanda and Raineri); and the
Department of Neurological Sciences (Roma) and the Institute NEUROMED (Pozzilli
IS), University of Rome "La Sapienza," Rome (Drs Vacca, Currà, and
Berardelli), Italy.
REFERENCES
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1. Berardelli A, Mercuri B, Priori A. Botulinum toxin for facial-oral-mandibular spasm and bruxism. In: Jankovic J, Hallet M, eds. Therapy With Botulinum
Toxin. New York, NY: Marcel-Dekker; 1994:361-367.
2. Wang A, Jankovic J. Hemifacial spasm: clinical findings and treatment. Muscle Nerve. 1998;21:1740-1747.
FULL TEXT
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ISI
| PUBMED
3. Yoshimura DM, Aminoff MJ, Tami TA, Scott AB. Treatment of hemifacial spasm with botulinum toxin. Muscle Nerve. 1992;15:1045-1049.
PUBMED
4. Geller BD, Hallet M, Ravits J. Botulinum toxin therapy in hemifacial spasm: clinical and electrophysiologic
studies. Muscle Nerve. 1989;12:716-722.
FULL TEXT
| PUBMED
5. Elston JS. The management of blepharospasm and hemifacial spasm. J Neurol. 1992;239:5-8.
PUBMED
6. Flanders M, Chin D, Boghen D. Botulinum toxin: preferred treatment for hemifacial spasm. Eur Neurol. 1993;33:316-319.
ISI
| PUBMED
7. Mauriello JA, Leone T, Dhillon S, et al. Treatment choices of 119 patients with hemifacial spasm over 11 years. Clin Neurol Neurosurg. 1996;98:213-216.
PUBMED
8. Van den Bergh P, Francart J, Mourin S, et al. Five-year experience in the treatment of focal movement disorders with
low dose Dysport botulinum toxin. Muscle Nerve. 1995;18:720-729.
PUBMED
9. Jitpimolmard S, Tiamkao S, Laopaiboon M. Long term results of botulinum toxin type A in the treatment of hemifacial
spasm: a report of 175 cases. J Neurol Neurosurg Psychiatry. 1998;64:751-757.
FREE FULL TEXT
10. Berardelli A, Abbruzzese G, Bertolasi L, et al. Guidelines for the use of botulinum toxin in movement disorders. Ital J Neurol Sci. 1997;18:261-269.
PUBMED
11. Digre K, Corbett JJ. Hemifacial spasm: differential diagnosis, mechanism and treatment. In: Jankovic J, Tolosa E, eds. Advances in Neurology. Vol 49. New York, NY: Raven Press; 1988:151-176.
12. Defazio G, Lepore V, Abbruzzese G, et al. Reliability among neurologists in the severity assessment of blepharospasm
and oromandibular dystonia: a multicenter study. Mov Disord. 1994;9:616-621.
PUBMED
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