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J Med Assoc Thai Vol. 87 No.10 2004 1205
Correspondence to : Suputtitada A, Department of Rehabili-
tation Medicine, Faculty of Medicine, Chulalongkorn Uni-
versity, Bangkok 10330, Thailand.
Hemifacial Spasm: Results of Treatment with Low Dose
Botulinum Toxin Injection
Areerat Suputtitada MD*, Kammant Phanthumchinda MD**,
Chaichon Locharernkul MD**, Nijasri C Suwanwela MD**
* Department of Rehabilitation Medicine, Faculty of Medicine, Chulalongkorn University
** Department of Medicine, Faculty of Medicine, Chulalongkorn University
Background : Hemifacial Sapsm (HFS) is a common movement disorder in Thailand. Botulinum toxin type A
(BTA) is an effective and safe treatment for this condition. The success of BTA treatment depends on the
experience of the clinician.
Objective : To study the demographic data, efficacy and safety of low dose BTA injection in HFS patients.
Setting : The Spastic and Dystonia Clinic, Department of Rehabilitation Medicine, King Chulalongkorn
Memorial Hospital.
Design : Open-label, prospective case-series study.
Patients : All patients with HFS referred for BTA injection from December 1
st
, 1995 to November 30
th
, 2003.
Method : Sex, age, side of spasm, onset of symptoms before BTA injection, underlying diseases, sites of BTA
injection, dose of each BTA treatment, duration of response, efficacy, and side-effects were analyzed. 3-5 units
of BOTOX were intramuscularly injected per site to all muscles that had spasm. After injection, a 20-minute
cold compression on the first day was followed by 20-minute warm compression with massage at each
injection site per day for 14 days.
Results : A total of 112 patients with HFS were treated with 874 BTA treatments. There were 71 females
(63.4%) and 41 males (36.6%). The mean age was 45 years. 75 patients (67%) were affected on the left side.
Mean duration of symptoms was 3.4 years. The sites of injection were orbicularis occuli and orbicularis oris
muscles in all 874 treatments (100%). The mean dose of all treatments was 25 units. The mean initial dose
was 30.5units.The mean dose for subsequent injection was 23 units. The mean duration between treatments
was 4.7 months. The mean initial duration was 3.5 months. The mean duration for subsequent injection was
4.8 months. The outcomes of treatment assessed at 4 weeks after injection classified as excellent (> 80%
improvement) were found in 845 treatments (96.7%). Most treatments had no complication (91.9%). Ptosis,
facial paresis and double vision were mild and transient, lasting 1-4 weeks. There were no long-term compli-
cations of BTA treatment in the present series.
Conclusion : Low dose BTA injection is an effective treatment for hemifacial spasm patients. There was a
longer duration of response in subsequent injections and a lower complication rate in the present study
when compared to others.
Keywords : Botulinum toxin, Hemifacial spasm
J Med Assoc Thai 2004; 87(10): 1205-11
e-Journal: http://www.medassocthai.org/journal
Hemifacial spasm (HFS) is clinically marked
by involuntary unilateral contraction of the muscular
system innervated by the facial nerve
(1)
. Its clinical
picture may vary substantially. Some patients may
merely present with contractions of the orbicularis
occuli muscle; in other patients, however, the entire
musculature innervated by the facial nerve including
platysma may be involved. Mild progression of the
symptom is seen in many cases
(1)
. HFS is often trig-
gered by fatigue, anxiety, stress, reading and driving;
it may persist during sleep
(2,3)
. Rarely, HFS can be
bilateral or familial
(2)
. HFS causes embarrassment and
an inferiority complex to the patient. In general, HFS
1206 J Med Assoc Thai Vol. 87 No.10 2004
is caused by mechanical compression by redundent
vessel and distortion of the root exit zone of the facial
nerve by an aneurysm which are regarded as idio-
pathic
(2,3)
. Lipoma, epidermoid tumor, arterio-venous
malformation have been found in less than 1% of the
cases
(2,3)
. Vessel-nerve contact results in mild facial
paralysis and may be demonstrated by MRI. Conven-
tional treatment with carbamazepine is only
occationally effective, and the side effect is unaccept-
able to many patients
(4)
. The surgical treatment is
vascular decompression of the facial nerve, which
usually gives excellent results (84%)
(5)
. However, com-
plications are serious, i.e. facial weakness (4.2%), tran-
sient facial weakness (3.2%), permanent hearing loss
(3.2%), brain stem infarct (0.3%), cerebellar hematoma
(0.5%), CSF leak (2.4%) and operative death (0.1%).
5
Since 1990, many studies have shown that
local injection of botulinum toxin is effective for HFS.
Different evaluation criteria had been employed in
these studies, making comparison difficult. In sum-
mary, good to excellent improvements were reported
in 76% to 100%
(6-8)
of these patients. The mean dura-
tion of action of each injection ranged between 2.6
and 4
(9,10)
months. The most common side effects were
dry eye 7% to 18.1%
(11,12)
ptosis 2.8% to 23.3%
(12,13)
facial weakness 17.6% to 97%
(13,14)
tearing 5.5%
(12)
and
diplopia less than 1% to 6%
(11,15)
. All of these undesired
effects were transitory, untoward systemic effects were
not quoted in any study. The conclusion is that botu-
linum toxin injections are safe and highly effective
treatment of HFS
(1)
.
The authors present here the long-term
results of efficacy and safety of low dose botulinum
toxin A (BTA) injection in HFS patients over an 8-year
period.
Objective
The objective was to study the demographic
data as well as efficacy and safety of low dose BTA
injection in HFS patients.
Study design
Open-label, prospective case-series study.
Patients and Method
All patients with HFS referred for BTA injec-
tion at the Spastic and Dystonia Clinic, Department of
Rehabilitation Medicine, King Chulalongkorn Memo-
rial Hospital, Bangkok, Thailand from December 1
st
1995
to November 30
th
, 2003 were analyzed. Demographic
data such as sex, age, side of hemifacial spasm, onset
of symptoms before BTA injection, underlying diseases
(hypertension, diabetes mellitus, heart disease,
stroke), history of Bell’s palsy, history of head trauma,
history of tinnitus, previous surgery (micro vascular
decompression of the facial nerve), sites of BTA in-
jection, dose of each BTA treatment, duration of re-
sponse, efficacy, immediate side-effects, long-term side
effects and spontaneous remission (no need for injec-
tion over two years) were reported. Data analysis were
presented as number (n) and percentage of patients,
mean + standard deviation (x + SD) and range.
Study drug
Botulinum toxin type A (BOTOX
®
, 100 unit
per vial, Allergan, INC) was reconstituted for injec-
tion to yeild 50 unit/ml by 0.9% sterile unpreserved
saline solution by the first author.
Injection technique and care after injection
With the patient in a lying position, the
injection sites (as shown in Fig. 1) were chosen by
clinical assessment of spasm. The injection sites were
cleaned with 70% alcohol and BOTOX was injected
intramuscularly 3-5 unit each site. A thirty gauge-needle
attached to a tuberculin syringe was used for injec-
tion. After injection, 20-minute cold compression on
the first day and then 20- minute warm compression
with massage at the injection sites for 14 days.
Assessment and follow-up
The outcomes of the treatment were assessed
by the investigators at 4 weeks after injection. They
were classified as excellent (> 80% improvement), good
(60-80% improvement), fair (20-60% improvement),
poor (1-20% improvement) and no improvement. In
X = 3-5 units per site
Injection sites:
1= Orbicularis occuli (upper medial
)
2= Orbicularis occuli (lower medial
)
3= Orbicularis occuli (lower lateral)
4= Orbicularis oris (upper)
5= Orbicularis oris (lower)
6= Zygomaticus
7= Nasalis
8= Mentalis
9= Platysma
10= Frontalis
11= Corrugator
Fig. 1 Demonstration of injection sites and botulinum toxin
usage
J Med Assoc Thai Vol. 87 No.10 2004 1207
addition, complications were assessed by the investi-
gators. Generally, appointment was made every three
months for each treatment, but the frequency of their
visits were adjusted to accommodate individual needs.
Results
A total of 112 patients with HFS were treated
with 874 BTA treatments during a period of 8 years.
The demographic data of all patients are shown in
Table 1.
There were 71 females (63.4%) and 41 males
(36.6%). The mean age of all patients was 45 + 11.1
years (range 24-67 years). Of the 112 HFS patients, 75
(67%) were affected on the left side. Their mean dura-
tion of symptoms before treatment was 3.4 + 3.1 years
(range 1-12 years). The mean follow-up period was 3.5
+ 2.5years (range 1-8 years). Several patients had
underlying diseases: hypertension in 12 patients
(10.71%), diabetes mellitus in 8 patients (7.1%), heart
disease in 8 patients (7.1%), and stroke in 2 patients
(1.8%). History of Bell’s palsy in 1 patient (0.9%),
tinnitus in 5 patients (4.5%), and history of microvas-
cular decompression of the facial nerve in 1 patient
(0.9%) were recorded.
The sites of injection were mostly orbicu-
laris occuli muscle in 874 treatments (100%), orbicu-
laris oris muscle in 874 treatments (100%), zygomati-
cus muscle in 468 treatments (53.5%), nasalis in 136
treatments (15.6%), mentalis in 168 treatments (19.2%),
platysma in 46 treatments (5.3%), frontalis in 42 treat-
ments (4.8%), and corrugator in 34 treatments (3.9%)
as shown in Table 2.
The mean dose of BOTOX
®
of all treatments
was 25 + 0.6 units (range 10-45 units) per injection.
There was decrement in the mean dose for each sub-
sequent injection. The mean initial dose was 30.5 + 0.4
units (range 20-45 units), the second 29.5 units, the
third 29 units, the fourth 28.5 units, the fifth 28 units,
the sixth 28 units, the seventh 28 units, the eight 27
units, the ninth 26 units, and the tenth 25 units. The
mean dose of subsequent injection was 27.5 + 0.5 units
(range 10-35 units) as shown in Table 3 and Fig. 2.
The mean duration of response of all treat-
ments was 4.1 + 0.4 months (range 3-6 months). The
durations also increased each subsequent injection.
The mean initial durations was 3.5 + 0.4 months (range
3-5 months), the second 3.8 months, the third 4.0
months, the fourth 4.1 months, the fifth 4.3 months,
the sixth 4.3 months, the seventh 4.4 months, the eight
4.5 months, the ninth 4.6 months, and the tenth 4.8
months. The mean duration of subsequent injection
was 4.8 + 0.4 months (ranged 3-6 months) as shown in
Table 3 and Fig. 3. There were 5 patients (8.9%) with
spontaneous remission (i.e. injection free interval
lasting more than two years).
Table 1. Demographic data of the all treatments
Sex: Male 41 patients 36.6%
Female 71 patients 63.4%
Age (yrs) 45 (SD 11.1)
range 24-72
Side of HFS Right 37 patients 33.0%
Left 75 patients 67.0%
Duration of symptoms 3.4 (SD 3.1)
before treatment (yrs) range 1-12
Follow up period (yrs) 3.45 (SD 2.45)
range 1-8
Associated conditions
History of Bell’s palsy 1 patient 0.9%
History of tinnitus 5 patients 4.5%
History of Microvascular 1 patient 0.9%
decompression
Underlying diseases
Hypertension 12 patients 10.7%
Diabetes mellitus 8 patients 7.1%
Heart disease 8 patients 7.1%
Stroke 2 patients 1.8%
Table 2. The sites of BOTOX
injection in 874 treatments
Muscles No. of Treatments
Orbicularis occuli 874 (100%)
Orbicularis oris 874 (100%)
Zygomaticus 468 (53.5%)
Nasalis 168 (19.2%)
Mentalis 136 (15.6%)
Platysma 46 (5.3%)
Frontalis 42 (4.8%)
Corrugator 34 (3.9%)
Table 3. Dose of BOTOX
and duration of response
n Mean range
Dose of BOTOX
of 874 25.0 (SD0.6) 10-45
all treatment (units)
Initial dose of BOTOX
112 30.5 (SD0.4) 20-45
(units)
Dose of subsequent 762 25.5 (SD0.5) 10-35
injection (units)
Duration of response of 874 4.7 (SD0.4) 3-6
all treatment (months)
Initial duration (months) 112 3.5 (SD0.4) 3-5
Duration of subsequent 762 4.8 (SD0.4) 3-6
injection (months)
1208 J Med Assoc Thai Vol. 87 No.10 2004
The outcomes of treatment assessed at 4
weeks after injection were classified as: excellent (>
80% improvement) in 845 treatments (96.7%), good
(60-80% improvement) in 25 treatments (2.9%), fair (20-
60% improvement) in 3 treatments (0.3%), poor (1-20%
improvement) in 1 treatment (0.1%) and no case with-
out improvement, as shown in Table 4.
There was no complication in most treatments
(91.9%). The immediate complications were ptosis
(2.9%), mild facial paresis (3%), double vision (1.7 %),
lacrimation (0.6%) and as shown in Table 5. These
complications were transient, lasting only 2-4 weeks.
There was no long-term complication of botulinum
toxin treatment in the present series.
Discussion
HFS usually appears between the fourth and
fifth decade of life
(16)
, as found in the present series
(i.e. mean age of the onset was 45 yrs). The spasm
most notably involves the orbicularis occuli, orbicu-
laris oris, zygomaticus, frontalis and mentalis muscles
on one side of the face
(16)
, as in the present series. As
the condition progresses, twitching becomes more
obvious on involuntary movement all ipsilateral facial
as well as the superficial muscles of the neck. Occa-
sionally, the involvement of the stapedius muscle of
the middle ear may cause the patients to have audi-
tory symptom characterized by a “thumping” or “click-
ing” noise associated with the spasm. Occasionally,
the patient may complain of tinnitus and hearing loss.
In our series, althrough injection at stapedius muscle
was not possible, the authors found that tinnitus and
clicking in the ear disappeared when injected BTA at
zygomaticus.
The response rate of the patients is compared
to other series in Table 6
(9,11,17-21)
. The presented data
showed 98% improvement that is also comparable to
the other series. The difference between the duration
of improvement and the dose are attributed to differ-
ent types of botulinum toxin (BOTOX vs Dysport),
differences in injection sites and techniques, differ-
ence in dose per injection site.
The mean dose of all treatments was 25 units,
similar to that of Poungvarin et al
(19)
but lower than
Table 4. Outcomes of treatments
Outcomes No of Treatments
Excellent (> 80%) 845 (96.7%)
Good (60-80%) 25 (2.9%)
Fair (20-60%) 3 (0.3%)
Poor (1-20%) 1 (0.1%)
No improvemt 0 (0%)
Table 5. Immediate side-effects of Botox injection
Side-effects No of Treatments
No complication 803(91.9%)
Mild ptosis 25(2.9%)
Mild facial paresis 26(3%)
Double vision 15(1.7%)
Excessive lacrimation 5(0.6%)
N1=112 patients; N2=105 patients; N3 = 102 patients; N4=99
patients; N5= 98 patients; N6= 95 patients; N7=86 patients;
N8= 75 patients; N9= 58 patients; N10= 44 patients
There was continuously decrement in mean dosage of
BOTOX
®
in subsequent injection
Fig. 2 Mean dosage of BOTOX
®
in each subsequent injection
0
5
10
15
20
25
30
35
Mean dosage of
BOTOXU
30.5 28.5 28 27.5 26 25.5 25 25 25 25
12345678910
N1=112 patients; N2=105 patients; N3 = 102 patients; N4=99
patients; N5= 98 patients; N6= 95 patients; N7=86 patients;
N8= 75 patients; N9= 58 patients; N10= 44 patients
There was increment in mean duration of response of
BOTOX
®
in subsequent injection
Fig. 3 Mean duration of BOTOX
®
in each subsequent
injection
0
2
4
6
Duration of
response
(Mo)
Times of subsequent injection
Mean duration of
response(Mo)
3.5 3.8 4 4.3 4.5 4.6 4.7 4.8 4.8 5.1
12345678910
J Med Assoc Thai Vol. 87 No.10 2004 1209
that of Flanders et al
(18)
. At the authors’ center, low-
dose regimen for every condition treated with BTA is
always used
(22-27)
. The possible explanations were: 1)
the smaller muscle mass of Thai patients; and 2) the
tropical climate in Thailand may facilitate extensibility
of the spastic muscle.
The mean dose in the initial treatment in the
present study (30.5 units) was higher than that of sub-
sequent treatments (25 units). The mean duration of
the initial treatment (3.5 months) was shorter than that
of subsequent treatments (4.8 months). These implied
that the severity of the symptoms seem to be lessened
with the subsequent treatments. Possible explanation
may be that: 1) there were adaptation of receptors of
the spastic muscles, 2) there was BTA accumulation
at the neuromuscular junction, and 3) there was no
clinical resistence over long-term subsequent injec-
tion. There was longer duration of response in the
present study when compared to others
(9,11,17-21)
.
Also, there was a lower complication rate in
the present study when compared to others
(9,11,17-21)
.
These may be due to: 1) lower dose of BTA used per
site, 2) different sites of injection were chosen, 3) the
cold and hot compression with massage which may
cause better diffusion of the toxin after injection.
Conclusion
Low dose BTA injection is an effective treat-
ment for hemifacial spasm. There was a longer dura-
tion of response in subsequent injections and a lower
complication rate in the present study when compared
to others.
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J Med Assoc Thai Vol. 87 No.10 2004 1211
ภาวะใบหน้ากระตุกครึ่งซีก: การรักษาด้วยการฉีดโบทูลินัมทอกซินขนาดน้อย
อารีรัตน์ สุพุทธิธาดา, กัมมันต์ พันธุมจินดา, ชัยชน โลว์เจริญกุล, นิจศรี ชาญณรงค์ สุวรรณเวลา
ปัญหา : ภาวะใบหน้ากระตุกครึ่งซีกเป็นภาวะการเคลื่อนไหวผิดปกติที่พบบ่อยในประเทศไทย การฉีดโบทูลนัมทอกซิน
มีประสิทธิภาพและปลอดภัยในการรักษาภาวะนี้ ผลสำเร็จของการฉีดโบทูลนัมทอกซินขึ้นกับประสบการณ์ของแพทย์
ผู้ทำการรักษา
วัตถุประสงค์: เพื่อศึกษาลักษณะทางคลินิกประสิทธิภาพและความปลอดภัยในการฉีดโบทูลนัมทอกซินขนาดน้อยใน
การรักษาภาวะใบหน้ากระตุกครึ่งซีก
สถานที่ที่ทำการศึกษา : คลินิกลดอาการเกร็งและบิดกระตุกของกล้ามเนื้อ ฝ่ายเวชศาสตร์ฟื้นฟู โรงพยาบาล
จุฬาลงกรณ์
รูปแบบการศึกษา : แบบไปข้างหน้า ติดตามผลการรักษาระยะยาว โดยไม่มีกลุ่มควบคุม
ผู้ป่วยที่ได้ทำการศึกษา : ผู้ป่วยใบหน้ากระตุกครึ่งซีกทุกรายที่ส่งมาเพื่อรับการฉีดโบทูลนัมทอกซิน ระหว่าง 1 ธันวาคม
2538 และ 3 พฤศจิกายน 2543
วิธีการศึกษา : เก็บข้อมูลผู้ป่วยด้าน อายุ เพศ ข้างที่มีใบหน้ากระตุก ระยะเวลานานของการมีอาการ โรคประจำตัว
ตำแหน่งฉีดยา ขนาดยา และระยะเวลาการออกฤทธิ์ของโบทูลนัมทอกซิน ประสิทธิภาพ และฤทธิ์ข้างเคียง ฉีดยา
BOTOX เข้าใต้ผิวหนัง 3-5 ยูนิต ต่อจุด ฉีดทุกจุดของกล้ามเนื้อที่กระตุก หลังฉีดประคบน้ำแข็ง 20 นาที ในวันแรก
และน้ำอุ่น 20 นาที ในวันต่อมา ทุกวันจนครบ 14 วัน พร้อมกับนวดคลึงตรงจุดที่ฉีดยาหลังประคบทุกวัน
ผลการศึกษา : ผู้ป่วยใบหน้ากระตุกครึ่งซีกทั้งหมด 112 ราย ได้รับการฉีดโบทูลนัมทอกซิน 874 ครั้ง เป็นหญิง 71
ราย (63.4%) ชาย 41 ราย (36.6%) อายุเฉลี่ย 45 ปี มีอาการกระตุกที่ใบหน้าซีกซ้าย 75 ราย (67%) ระยะเวลาเฉลี่ย
ตั้งแต่ เริ่มมีอาการ 3.4 ปี ตำแหน่งฉีดยาส่วนใหญ่ คือ กล้ามเนื้อ orbicularis occuli และ orbicularis oris ทั้งสองตำแหน่ง
ตำแหน่งละ 874 ครั้ง (100%) ขนาดยาเฉลี่ยของการรักษาทั้งหมด 25 ยูนิต ขนาดยาเฉลี่ยของการรักษาครั้งแรก 30.5
ยูนิต ครั้งต่อมา 23 ยูนิต ระยะเวลาเฉลี่ยของการตอบสนองของยาของการรักษาทั้งหมด คือ 4.7 เดือน ระยะเวลาเฉลี่ย
ของการรักษาครั้งแรก คือ 3.5 เดือน ครั้งต่อมา คือ 4.8 เดือน ผลการรักษาเมื่อประเมิน 4 สัปดาห์หลังฉีดยาพบว่า
ได้ผลดีมาก (ดีขึ้น >80%) ถึง 845 ครั้งของการรักษา (96.7%) การรักษาส่วนใหญ่ไม่พบฤทธิ์ข้างเคียงอันไม่พึงประสงค์
(91.9%) ได้แก่ อาการหนังตาตก ใบหน้าอ่อนแรง หรือเห็นภาพซ้อน ที่พบจะไม่รุนแรง และอยู่ชั่วคราวเพียง 1-4 สัปดาห์
ไม่พบฤทธิ์ข้างเคียงใด ๆ ระยะยาว
สรุป : การฉีดโบทูลนัมทอกซินขนาดน้อยเป็นการรักษาภาวะใบหน้ากระตุกครึ่งซีกที่มีประสิทธิภาพ และพบว่า
ระยะเวลานาน ในการออกฤทธิ์ของยาเมื่อฉีดครั้งต่อมาจะยาวนานกว่า และฤทธิ์ข้างเคียงอันไม่พึงประสงค์น้อยกว่า
เมื่อเทียบกับ การศึกษาอื่น
