Journal of Clinical Neuroscience xxx (2015) xxx–xxx

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Journal of Clinical Neuroscience

journal homepage: www.elsevier.com/locate/jocn

Clinical Study

Botulinum toxin injections for the treatment of hemifacial spasm over

16 years
Mine Hayriye Sorgun a,⇑, Rezzak Yilmaz b, Yusuf Alper Akin a, Fatma Nazli Mercan a,
Muhittin Cenk Akbostanci a
a _
Department of Neurology, Ankara University School of Medicine, Ibni Sina Hospital, Samanpazarı, Ankara, Turkey
b
Deptartment of Neurodegeneration, Centre for Neurology and Hertie Institute for Clinical Brain Research, Tübingen University School of Medicine, Tübingen, Germany

a r t i c l e i n f o a b s t r a c t

Article history: The aim of this study was to investigate the efficacy and side effects of botulinum toxin (BTX) in the treat-
Received 24 January 2015 ment of hemifacial spasm (HFS). We also focused on the divergence between different injection tech-
Accepted 14 February 2015 niques and commercial forms. We retrospectively evaluated 470 sessions of BTX injections
Available online xxxx
administered to 68 patients with HFS. The initial time of improvement, duration and degree of improve-
ment, and frequency and duration of adverse effects were analysed. Pretarsal and preseptal injections and
Keywords: Botox (Allergan, Irvine, CA, USA) and Dysport (Ipsen Biopharmaceuticals, Paris, France) brands were com-
Botox
pared in terms of efficacy and side effects, accompanied by a review of papers which reported BTX treat-
Botulinum toxin
Dysport
ment of HFS. An average of 34.5 units was used per patient. The first improvement was felt after 8 days
Hemifacial spasm and lasted for 14.8 weeks. Patients experienced a 73.7% improvement. In 79.7% of injections, no adverse
effect was reported, in 4.9% erythema, ecchymosis, and swelling in the injection area, in 3.6% facial asym-
metry, in 3.4% ptosis, in 3.2% diplopia, and in 2.3% difficulty of eye closure was detected. Patients reported
75% improvement on average after 314 sessions of pretarsal injections and 72.7% improvement after 156
sessions of preseptal injections (p = 0.001). The efficacy and side effects of Botox and Dysport were sim-
ilar. BTX is an effective and safe treatment option for HFS. No difference was determined between Botox
and Dysport, and pretarsal injection is better than preseptal injection regarding the reported degree of
improvement.
Ó 2015 Elsevier Ltd. All rights reserved.

1. Introduction gabapentin have been shown to be effective in the symptomatic

Hemifacial spasm (HFS) is characterised by involuntary parox-
ysmal clonic or tonic contractions of muscles innervated by the
facial nerve on one side of the face [1]. Generally, it is caused by
axonal–axonal ephaptic transmission and ectopic excitation due
to vascular cross-compression at the root exit zone of the facial
nerve [2]. HFS seems more common in females than males with
a prevalence of 14.5/100,000 and 7.4/100,000, respectively [3].
Regarding causality of HFS, hypertension is related to vascular
tortuosity in the cerebellopontine angle [4].
A combination of mild facial palsy and mild narrowed palpebral
fissure are characteristic of HFS. Differential diagnoses of HFS
include facial myokymia, facial tics, blephoraspasm, synkinesis
and aberrant regeneration after Bells’ palsy and psychogenic facial
movements [5]. Anticonvulsants such as carbamazepine or
⇑ Corresponding author. Tel.: +90 5438900934.
E-mail address: drmsorgun79@yahoo.com.tr (M.H. Sorgun).
treatment of HFS [6,7] and selected patients are treated by
microvascular decompression [8]. For the symptomatic treatment
of HFS, injections of botulinum toxin (BTX) have been proven effec-
tive and are increasingly used worldwide. Here, we report our own
experience in addition with a review of the literature for the past
30 years.
2. Patients and methods
Between July 1996 and July 2012, 113 patients (68 women, 45
men) with HFS were retrospectively analysed. The mean age of
patients was 63.1 years. Forty-five patients had only one injection
per session in a total number of 514 sessions. Data for the 68
patients who had at least two injections per session were further
analysed. The latency, duration and degree of improvement
(assessed by the visual analogue scale [VAS]: subjective evaluation
of degree of amelioration of spasms from 0 to 100% by the patient
with 0% being no effect and 100% being asymptomatic), and

http://dx.doi.org/10.1016/j.jocn.2015.02.032
0967-5868/Ó 2015 Elsevier Ltd. All rights reserved.

Please cite this article in press as: Sorgun MH et al. Botulinum toxin injections for the treatment of hemifacial spasm over 16 years. J Clin Neurosci (2015),
http://dx.doi.org/10.1016/j.jocn.2015.02.032
2 M.H. Sorgun et al. / Journal of Clinical Neuroscience xxx (2015) xxx–xxx

were never injected in the first session and were only injected
afterwards if the patient still complained of perioral spasms.

3. Results

In our cohort, 470 sessions of BTX injections were applied to 68

patients with a mean of 6.9 sessions per patient (range: 2–27). An
average value of 34.5 units (range: 19.5–85; Botox equivalent
dose) were used. On average, patients felt the first improvement
after 8 days (range: 1–40) and they returned to their
pre-injection condition after 14.8 weeks (range: 1–22). Patients
expressed a 73.7% (range: 0–100) improvement on average in the
VAS. No adverse effects were observed in 79.7% of injections.
Detected side effects were 4.9% erythema, ecchymosis, and swel-
ling in the injection area, 3.6% facial asymmetry, 3.4% ptosis, 3.2%
diplopia, and 2.3% difficulty of eye closure. Ocular pain, blurred
vision, nasal bleeding, temporary increase in spasms, conjunctival
hyperaemia on the injection side, conjunctival hyperaemia on the
non-injected eye, and dry eyes were reported in less than 1% of
the sessions (Table 1).
With regard to the injection site, our patients reported 75%
improvement on average after 314 sessions of pretarsal injections
and 72.7% improvement after 156 sessions of preseptal injections
(Student’s t-test p = 0.001). Adverse effects were seen in 19.7% of
pretarsal injections and 16.7% of preseptal injections (chi-squared
test p = 0.42; Table 2).
When comparing commercial brands, the average improvement
was 74.3% with Botox in 460 sessions and 76.3% with Dysport in 10

Table 1
Adverse effects of botulinum toxin in hemifacial spasm patients
Fig. 1. Schematic representations of (A) preseptal and (B) pretarsal injection
techniques. The black oval dots indicate the injection points. Adverse effect Frequency, %
None 79.7
frequency and duration of the side effects were analysed. Pretarsal Erythema, ecchymosis, and swelling in the injection area 4.9
Facial asymmetry 3.6
and preseptal injections and the commercial brands Botox
Ptosis 3.4
(Allergan, Irvine, CA, USA) and Dysport (Ipsen Biopharmaceuticals, Diplopia 3.2
Paris, France) were compared in terms of the parameters men- Difficulty of eye closure 2.3
tioned above (Fig. 1). The dose equivalence of Botox and Dysport Other effects
was calculated as 1/5. We did not use a strength conversion ratio Ocular pain 0.3
between Botox and Dysport in accordance with the results of Blurring in vision 0.3
previous reports [9]. Prickling in forehead 0.3
Nasal bleeding 0.3
For the first session, all patients were injected with 5 units of
Temporary increase in spasms 0.3
Botox or 15 units of Dysport per site as shown in Figure 1. Doses Conjunctival hyperaemia on the injection side 0.8
were adjusted in upcoming sessions in accordance with the effec- Conjunctival hyperaemia on the non-injected eye 0.3
tiveness and side effects of the previous session. Perioral muscles Dry eyes 0.3

Table 2
Efficacy and adverse effects of pretarsal versus preseptal botulinum toxin injection applications and Botox versus Dysport brand

Patients with HFS, n = 68

Total sessions, n = 470
Botoxa Dysportb p value Pretarsal Preseptal p value
Age, year, mean ± SD 63 ± 14.4 64 ± 7.2 0.13 64 ± 14.3 62 ± 14.1 0.92
Sex, n (%) 0.45 0.84
Female 36 (55.4) 1(33.3) 17 (53.1) 20 (55.6)
Male 29 (44.6) 2 (66.7) 15 (46.9) 16 (44.4)
Total sessions, n (%) 460 (97.9) 10 (2.1) NC 314 (66.8) 156 (33.2) NC
Doses as units, mean ± SD 33.8 ± 13.5 49.7 ± 21.9 0.19 39.1 ± 18.3 30.4 ± 6.9 <0.0001
First improvement (days), mean ± SD 8.1 ± 7.0 1.0 ± 0.0 NC 8.6 ± 8.8 7.5 ± 4.9 0.21
Improvement on VAS, % 74.3 76.3 0.86 75 72.7 0.001
Adverse effects, % 18.7 20 0.92 19.7 16.7 0.42
a
Allergan, Irvine, CA, USA.
b
Ipsen Biopharmaceuticals, Paris, France.
HFS = hemifacial spasm, NC = not calculated, SD = standard deviation, VAS = visual analog scale.

Please cite this article in press as: Sorgun MH et al. Botulinum toxin injections for the treatment of hemifacial spasm over 16 years. J Clin Neurosci (2015),
http://dx.doi.org/10.1016/j.jocn.2015.02.032
 M.H. Sorgun et al. / Journal of Clinical Neuroscience xxx (2015) xxx–xxx 3

sessions (Mann–Whitney u-test p = 0.86). The frequency of the side
effects was 18.7% with Botox and 20% with Dysport (Fisher’s exact
test p = 0. 92; Table 2).
4. Discussion
Since the first introduction of BTX for the treatment of HFS by
Mauriello and Elston [10,11], voluminous studies have confirmed
the efficacy and safety of this application. We systematically reviewed
and documented the results of the reported series and compared these
with the results from our own patient cohort (Table 3).
4.1. Search strategy
The search we conducted was within the PubMed electronic
database for articles published between January 1985 and
November 2014. The terms ‘‘hemifacial spasm’’, ‘‘facial hemis-
pasm’’ and ‘‘craniocervical dystonia’’ were sought in the title of
the studies. Reports in languages other than English, case reports
and reviews were excluded as well as studies which did not focus
on BTX treatment and those that reported results of etiology, qual-
ity of life or surgical treatment of HFS. Details of search strategy
and exclusion criteria are depicted in Figure 2. A total of 64 studies
with full texts and 32 studies with abstracts were systematically
reviewed.

Table 3
Selected studies of botulinum toxin treatment in hemifacial spasm patients

Study (first author, Patients Follow-up Age Latency of Duration of Degree of Most Frequency of
year) (n) (mean) (mean improvement improvement improvement frequent side side effect, %
years) (mean days) (mean and rating scale used effect (variable)
weeks)
Berardelli 1993 [25] 83 NR 57.4 4.8 10 62% benefit in Marsden and Mild ptosis 22.8 (patient)
Schachter score
Park 1993 [27] 101 7– 53.3 4 16.5 98.4% of patients with excellent Dry eye 19.8 (patient)
20 months result in subjective grading scale
Laskawi 1994 [60] 29 22.5 weeks 59.5 4.7 18.2 94.7% of patients improved (SE) Incomplete lid 20 (injection)
closure
Van den Bergh 1995 [22] 40 22 months 55 7 17.1 On the 13 point composite scale, Ptosis, facial 22 (injection)
score dropped to 1.4 from 12 weakness
Poungvarin 1995 [26] 42 2–3 years 51.9 NR 8–16 80.9% of patients had excellent Facial 7.14 (patient)
improvement (SE) weakness
Lorentz 1995 [52] 66 14 months 57 NR 18 89.2% of patients rated good to Dry eye, lower 19.6 (patient)
excellent facial
weakness
Mauriello 1996 [5] 119 30 months 65 NR 16–18 80% improvement in spasms in all NR NR
patients (SE)
Kwan 1998 [31] 130 NR 50–60 7–14 12 81.7% of patients showed good Ptosis 9.2 (patient)
responses
Wang 1998 [1] 158 17.7 months 59.95 5.4 18.4 Marked to moderate improvement Facial 15.8 (patient)
in 95% of patients on subjective weakness
scale
Jitpimolmard 1998 [21] 175 2.4 years 49.10 NR 13.6 97% improvement in all treatments Ptosis 22.10 (treatment)
(VAS)
Thussu 1999 [33] 27 NR 47.7 3.07 17.8 3.78 point improvement in Ptosis 4.39 (injection)
Jankovic disability rating scale
Rollnik 2000 [46] 21 2 years 59.0 6.6 13.1 3.0 points improvement rated by Ptosis 9.5 (patient)
patient (GCI)
Defazio 2002 [42] 65 10 years 61.0 NR 12.6–13.5 96% improvement in all patients Upper lid 8–23 (patient)
(SE) ptosis
Gupta 2003 [34] 62 3.7 years 46.5 4.1 24.3 96.7% of patients improved on Pain 4.8 (patient)
functional status scale
Poonyathalang 2005 [20] 26 13.6 months 56.7 2 16.3 All patients showed more than 70% Mild ptosis 3.8 (patient)
improvement (SE)
Cannon 2010 [5] 34 7.5 years 60.8 NR 21 90% of patients were satisfied Ptosis n = 2 patients
Quagliato 2010 [24] 36 16 weeks 59.3 NR 12.9 94.6% of patients had good to Facial 70–73.5 (patient)
excellent improvement weakness
Barbosa 2010 [43] 54 5.9 years 48.3 NR 13.2 78.6–83.18% improvement in Orbicularis 38.8 (patient)
patients oris paralysis
Rudzinska 2010 [18] 56 12 weeks 60 7 NR 80.3% of the patients had a marked Facial 9 (patient)
moderate effect weakness
Cillino 2010 [35] 58 10 years 71.7 2.7 20.6 All patients improved 98% (SE) Upper lid 17.2 (patient)
ptosis
Kollewe 2010 [14] 97 6 years 37–93 7.2 12.2 92% of patients were stable in GCI Ptosis 2.3–2.8 (injection)
Setthawatcharawanich 53 2.9 years 55 NR NR 83.3% improvement in all patients Tearing, ptosis 9.7 (patient)
2011 [57] (VAS)
Bentivoglio 2012 [37] 108 NR 51.6 4 17.1 4.4 point improvement in global NR NR
rating scale for all patients
Wu 2011 [19] 273 5 years 45.5 4.4–4.1 16.2–16.5 84–94% of patients had complete or Tightness in 15.9–21.1
obvious remission in Cohen’s scale face (patient)
Wang 2014 [68] 1003 5 months 46.6 5 19.5 95.8% of patients improved 3–4 Droopy mouth 22.0 (patient)
points on the Jankovic scale
Our study 2014 68 2.1 years 63.1 8 14.8 73.7% improvement in all Ptosis 3.4 (patient)
patients (VAS)

GCI = global clinical improvement, NR = not reported, SE = subjective evaluation, VAS = visual analog scale.

Please cite this article in press as: Sorgun MH et al. Botulinum toxin injections for the treatment of hemifacial spasm over 16 years. J Clin Neurosci (2015),
http://dx.doi.org/10.1016/j.jocn.2015.02.032
4 M.H. Sorgun et al. / Journal of Clinical Neuroscience xxx (2015) xxx–xxx
Fig. 2. Flow chart of the database search strategy for this study.
4.2. Overview
Most of the studies that we reviewed reported similar results
with high efficacy and temporary adverse effect profiles.
However, there were differences in study designs in terms of injec-
tion site or BTX dosage, follow-up period and especially in the eval-
uation of the improvement. In the literature, the degree of
improvement has been reported in several ways including the per-
centage of patients that improved or percentage of injections that
showed improvement. Moreover, the percentage or the degree of
improvement of spasms on a given scale varies profoundly. The
reviewed studies used the following measures: modified Jankovic
rating scale [12] (score 0–4 from no sign to severe spasms), subjec-
tive improvement scale (score 0–3 from no improvement to max-
imal improvement) [13], global clinical improvement scale (score
0–3 from no improvement to marked improvement) [14], Fahr–
Marsden scale (score 0–4 from no dystonia to dystonia at rest)
[15], global rating scale (score 0–6 from no effect to complete res-
olution) [16], hemifacial spasm rating scale (score 0–4 from no
spasm to marked spasm or eye closure) [17], clinical global
impression-severity scale [18] (score 0–7 from normal to extre-
mely ill), Cohen’s scale (score 0–4 from no spasm to severe spasm)
[19], or in most of the reviewed studies, the VAS [20,21].
Additionally, some used a composite scale including several rating
scales and video images and the mean value of the scale results
[22]. Moreover, some studies used an arbitrary scale of satisfaction
[23] or a qualitative evaluation such as good or excellent improve-
ment [24]. Although most are quite similar, the variety of scales
and evaluation methods complicates the assessment of the degree
of improvement for reviews.
Of the reviewed studies, some reported two or more results
with regard to the degree of improvement, duration of improve-
ment or side effects within their follow-up periods. Furthermore,
some multicenter studies reported differences in the outcomes of
the centers involved [25]. In those studies, arithmetical means of
the results were calculated and taken out as a single value.
Please cite this article in press as: Sorgun MH et al. Botulinum toxin injections for the treatment of hemifacial spasm over 16 years. J Clin Neurosci (2015),
http://dx.doi.org/10.1016/j.jocn.2015.02.032
According to our review of the literature for the last 30 years,
three to 1003 patients with ages ranging 48–73 years were fol-
lowed from 1 month to 16.8 years. There were also three placebo
controlled double-blind studies on the efficacy of BTX in HFS
[26–28].
4.3. Latency and duration of improvement
The latency of improvement was between 2 and 14 days in the
literature [14,18,20,25,27,29–37] and 8 days in our patient cohort.
The mean duration of improvement calculated from the literature
review was 15.7 weeks (range: 6.5–24.3) [14,20,21,25–51], similar
to our result which was 14.8 weeks.
4.4. Degree of improvement
According to the literature, 94.3% of the patients (range: 84–
100) reported an 86.7% improvement (range: 73–96.9) in their
spasms (measured by VAS) [18,20,21,25–31,35,36,38–40,42,43,
52–60]. The degree of improvement in our patients was 73.7%. As
mentioned above, studies that used other scales for the evaluation
of the degree of improvement could not be added to the data-pool
for analyses. However, those studies reported similar values such
as a value of 4.4 on the global rating scale indicating an improve-
ment of approximately 70% [16], or dropping of the composite
score from 12 to 1.4 indicating a marked improvement [22], or a
score of 2.6 on the global clinical improvement scale in 92% of
patients which means more than moderate improvement in the
spasm severity and function [14]. The literature review of the effi-
cacy of BTX treatment revealed satisfactory results; we have found
no study that reported failure in the majority of patients. However,
not all of the patients benefitted from the injections. The etiology
of HFS may be the reason behind the ineffectiveness in some indi-
viduals or the variability of good responses. For example, it has
been reported that in contrast to anterior inferior cerebellar artery
compression, patients with vertebral artery compression are
 M.H. Sorgun et al. / Journal of Clinical Neuroscience xxx (2015) xxx–xxx 5

Table 4
Studies comparing efficacy of botulinum toxin brands Botoxa and Dysportb for treatment of hemifacial spasm

Study (first author, year) Conversion Brand n Duration of Degree of improvement Side effect frequency Conclusion
ratio B:D improvement and scale used
Sampaio 1997 [30] 4:1 Botox 22 patients 13.9 weeks NR 47% of patients No difference
Dysport 27 patients 13.4 weeks 50% of patients
c
Bihari 2005 [56] 5:1 Botox 9 patients 65.1 days* 77% VAS 0 Botox
Dysport 41.8 days 60% VAS 5 patients
Bentivoglio 2009 [36] 4:1 Botox 492 sessions 85.4 days NR 16.7% of patients No difference
Dysport 173 sessions 105.9 days* 19.7% of patients
Kollewe 2010 [14] 2.56:1 Botox 53 patients 12.1 weeks 2.6 GCI 5.2% of patients No difference
Dysport 44 patients 12.2 weeks 2.6 GCI 5.8% of patients
Our study 2014 5:1 Botox 460 sessions NR 75% VAS 18.7% of sessions No difference
Dysport 10 sessions 73% VAS 20% of sessions
*
p < 0.05.
a
Allergan, Irvine, CA, USA.
b
Ipsen Biopharmaceuticals, Paris, France.
c
Crossover design.
B = botox, D = Dysport, GCI = global clinical improvement, NR = not reported, VAS = visual analog scale.

refractory to BTX treatment [61]. The etiology of the spasms should
be taken into account for evaluating the degree of improvement
and in patients with poor responses.
4.5. Side effects
In HFS, side effects of BTX were usually mild and transient and
improved within at most a month. Reported side effects were pto-
sis, facial weakness, diplopia, dry eyes, periorbital edema, epi-
phora, bruising and local hematoma [25,30–33,35,38,
41,52,55,62–68]. Facial weakness was reported as facial asymme-
try or mouth droop in different studies [27,31,69]. Unexpected side
effects such as keratitis [38] or nausea [69] were rare.
The frequency of side effect varied widely in percentage. The
most frequently reported side effect was ptosis with a mean value
of 23.7% of injections (range: 2.5–72.2), followed by a mean value
of 26.8% for facial weakness (range: 4.5–76.9).
The degree or duration of the side effects may be related to sev-
eral factors. In elderly patients, the toxin may expand to a larger
area with the help of loose connective tissue [27], therefore, age
may be a factor. The injection site has also been shown to be asso-
ciated with side effects; inner orbital injections were related to a
higher incidence of ptosis [21,70]. Finally, side effects have been
shown to be related to dosage and in studies with longer
follow-up periods decreases in the frequency of side effects were
reported as the dosage of injections decreased [23,42].
4.6. Botox versus Dysport
Several brands of BTX are now available in the worldwide mar-
ket and studies comparing brands with Botox or Dysport have
recently been published [19,24,58]. However, the most widely
used commercial products are still Botox and Dysport. These two
brands were compared in five Class IV studies with a total of 371
patients with HFS. One retrospective study found longer improve-
ment with Dysport [35], another non-randomised cross-over study
reported the opposite and concluded the superiority of Botox [56].
No difference in efficacy was found in another two
non-randomised studies [14,16]. For the comparison of these two
brands in HFS, there is only one randomised prospective study
which found no significant differences [30]. Our experience is in
accordance with this result, the average degrees of improvement
and side effect rates were similar. In light of this literature review,
current evidence argues against a difference in the two commercial
labels, Botox and Dysport, for the treatment of HFS (Table 4).
4.7. Pretarsal versus preseptal injections
From the introduction of BTX treatment for HFS, several differ-
ent injection locations were tested in order to gain more efficacy
and to minimalise side effects [21,70]. Regarding injections of the
eyelid, our own experience shows that pretarsal injections yield
better improvement and fewer side effects than preseptal ones.
Our result was also previously confirmed with a prospective study
in patients with blepharospasm and HFS [71]. Cakmur et al.
reported higher response rates with longer durations of improve-
ment and fewer side effects with pretarsal injections. The pretarsal
area of the orbicularis oculi muscle is responsible for reflex and
spontaneous blinking and it has been suggested that with presep-
tal injections the diffusion of BTX to the tarsal area may be inade-
quate compared to direct pretarsal injections. Additionally, the
distance between the injection site and the neuromuscular junc-
tions of the levator palpebrae muscle is greater in pretarsal injec-
tions, which may explain less ptosis side effects [71].
In the present study, we retrospectively evaluated 470 sessions
of BTX injections with Botox and Dysport in a series of 68 HFS
patients during a period of 16 years. Our results were in accor-
dance with our review of the data from the past 30 years of
literature.
5. Conclusion
In summary, for the symptomatic treatment of HFS, BTX is the
first choice treatment with a latency of improvement of 2–14 days,
duration of improvement of 15–16 weeks, 85% degree of improve-
ment in VAS, transient and mild ptosis and facial weakness as the
most common side effects, no difference between the leading
brands Botox and Dysport and better results with pretarsal, rather
than preseptal, injections.
Conflicts of Interest/Disclosures
The authors declare that they have no financial or other con-
flicts of interest in relation to this research and its publication.
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http://dx.doi.org/10.1016/j.jocn.2015.02.032
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Please cite this article in press as: Sorgun MH et al. Botulinum toxin injections for the treatment of hemifacial spasm over 16 years. J Clin Neurosci (2015),
http://dx.doi.org/10.1016/j.jocn.2015.02.032