J Neurol (1992) 239 : 5-8
Journal of
Neurology © Springer-Verlag1992
The management of blepharospasm and hemifacial spasm John S. Elston* National Hospital for Neurology and Neurosurgery, Queen Square, London WCIN 3BG, UK Received November 5, 1990 / Received in revised form March 28, 1991 / Accepted April 22, 1991
Summary. The aetiology of blepharospasm and hemifacial spasm is different, but both produce involuntary eye closure and facial movements which do not respond to systemic drug treatment. The introduction of therapeutic focal muscle weakening with botulinum toxin injections in the early 1980s appeared to offer great promise in the management of these conditions. In this paper the results of botulinum toxin treatment of 234 patients with blepharospasm and 73 patients with hemifacial spasm over a 7-year period have been analysed. Most patients receive sustained benefit from repeated injections whilst side-effects become less frequent. A clinically recognisable subgroup of patients with blepharospasm respond poorly and may be better treated surgically. Key words: Idiopathic blepharospasm - Hemifacial spasm - Botulinum toxin
Introduction Idiopathic blepharospasm - forceful involuntary contraction of the periocular facial muscles - is a chronic disease, primarily affecting patients in the 5th and 6th decades and severely impairing vision in the majority of cases. Driving, reading and even unaccompanied walking are compromised, making work difficult or impossible; recreational activities requiring vision, such as watching television or gardening, are curtailed. Disfiguring periocular spasms often extend into the face, jaw or neck, and restrict social activities [10]. In its early stages the condition is often misdiagnosed and the symptoms excessive blinking and discomfort or grittiness of the eyes - are ascribed to ocular surface disorders, such as eyelid infections or dry eyes. There is evidence that blepharospasm may co-exist with such disorders and possibly be precipitated by them [7]. Alternatively the condition may be ascribed to stress or hysteria. The early symptoms and signs evolve into spasms of eye closure, * Present address and address for offprbzt requests: The Eye Hospital, Radcliffe Infirmary, Woodstock Road, Oxford OX2 6HE, UK
but even in established cases, because of unpredictable variations in severity, and the absence of a demonstrable cause some doctors still regard the condition as primarily psychiatric or hysterical [1]. There is, however, considerable evidence for an organic aetiology. For example, the clinical spectrum of the disorder may range from isolated periocular spasms to include associated oromandibular or neck spasms (including spasmodic torticollis) or a generalized movement disorder, such as torsion dystonia. Typical blepharospasm has also been described as part of neuroradiologically proven secondary dystonia [11]. However, systemic drug treatment to correct a presumed central neurochemical imbalance is largely unsuccessful. Surgical treatment, either facial nerve avulsion or orbicularis oculi excision may be successful but at a considerable cosmetic and functional cost to the patient. The first reports of a simple safe and effective local treatment for blepharospasm - focal orbicularis oculi denervation with botulinum toxin injections - were therefore of considerable importance, principally because of the relief afforded to patients [6]. Also, the reports have widely publicised the condition and led to increased awareness, more accurate diagnosis and more sympathetic management and appropriate referral amongst the medical profession. At specialist centres the opportunity to study large numbers of patients has provided further clinical and electrophysiological evidence for an organic aetiology for blepharospasm [3]. Hemifacial spasm consists of intermittent synchronous contraction of ipsilateral seventh cranial nerve innervated muscles. Typically the spasms begin in the orbicularis oculi in patients aged in their 40s and 50s and spread to the brow, mid and lower face and neck (platysma) over several years. Spasms are often worse when the patient is anxious, but unless vision is poor in the contralateral eye they do not interfere with work or other activities [8]. However, hemifacial spasm is intractable and a considerable social embarrassment. There is some evidence that microvascular compression of the seventh nerve in its root exit zone in the posterior fossa may be responsible and surgical decompression may be curative [2]. Systemic drug treatment is
largely ineffective, but botulinum toxin injections have p r o v e d to b e h e l p f u l a n d well t o l e r a t e d . This p a p e r d r a w s o n e x p e r i e n c e o f b o t u l i n u m t o x i n treatment of idiopathic blepharospasm and hemifacial s p a s m f r o m 1983 to 1990 a n d a t t e m p t s to d e f i n e its r o l e in t h e l o n g - t e r m m a n a g e m e n t o f t h e s e p a t i e n t s a n d to e x a m i n e w h e t h e r t h e e a r l y p r o m i s e has b e e n fulfilled.
Patients, materials and methods A total of 307 patients have been treated, 234 with blepharospasm and 73 with hemifacial spasm. Of the 234 patients with blepharospasm, 194 (group I) were treated at one centre and have been previously reported [5]. Fourteen of these patients, and 40 new cases (group II) have been treated at another centre. The longest followup period is 7 years (40 sets of injections), the shortest 6 months (2 sets of injections). The patients were classified as having blepharospasm alone or in association with spasms in the mid and lower face, jaw (ormandibular dystonia), neck or elsewhere (blepharospasm plus). Eighteen patients in group I and 3 in group II had a generalized movement disorder. The patients' practical visual function was assessed by the examiner using clinical observation and the results of a standard questionnaire and then graded from 1 to 6 (see Table 2). Category 1 indicates that the patients' eyes are shut all the time; in category 2, the eyes cannot be opened out of doors, but open intermittently indoors. Category 3 patients can open their eyes for periods that enable them to be independent of other people out of doors, and in category 4 this independence extends to being able to continue work but not drive a car or use the eyes recreationally (e.g. reading, watching television). These
activities would be possible, but not for long periods or comfortably in category 5, whilst category 6 is normal. The categorization was agreed with the patient before treatment and at every clinic afterwards, taking the average functional result over the intervening period. The effect of the treatment on the spasm distant from the site of injection in blepharospasm plus was evaluated. In group II patients were designated before treatment as having typical or atypical blepharospasm. Typical was defined as forceful bilateral spasms of eye closure, the muscles involved including the orbital orbicularis oculi with lowering of the brows during spasms. In atypical cases, the eyes were shut but clinically obvious forceful contraction was absent, except when the observer tried to open the eyes. Orbital orbicularis spasm was absent, and the brows were often elevated with the patients complaining of difficulty initiating opening of the eyes (8 cases). The results of treatment of 42 out of the 73 patients with hemifacial spasm (group I) have been published [5]. Three of these patients, and 31 new cases have been assessed and treated (see Table 3). The percentage reduction in abnormal movements and duration of response was measured as before. Patients in group I (both blepharospasm and hemifacial spasm) were treated as previously described [5]. In group II, the number of injections was reduced from 4 to 3, omitting the medial lower lid injection, and the treatment was given further from the lid margin into the orbital orbicularis oculi. However, a l n g dose in 0.2 ml sterile saline was given at each injection site, and the total dosage was therefore the same. (Botulinum toxin courtesy of Dr. Peter Hambleton, Centre for Applied Microbiological Research, Public Health Laboratory Service, Porton Down, UK). For second and subsequent treatments, 0.5ng in 0.1 ml saline was injected as required.
Results Table 1. Blepharospasm No.
Group I Group II
Male
Female
Onset age (average)
Blepharospasm Alone Plus
194
70
124
60.6
38
156
40 + 14
10
30
55.5
19
21
Table 2. Blepharospasm: grading of functional status Category
Visual function
1 2 3 4 5 6
Blind Dependent outside home Independent: poor function Independent: moderate function Inconvenienced Normal
Blepharospasm T h e visual d i s a b i l i t y score b e f o r e t r e a t m e n t a n d o n average after t r e a t m e n t a r e r e c o r d e d in T a b l e 4. T h e figures in b r a c k e t s in g r o u p I I s h o w cases of a t y p i c a l b l e p h a r o spasm. O f 156 p a t i e n t s in g r o u p I with b l e p h a r o s p a s m plus, a n d a g o o d r e s p o n s e to t r e a t m e n t ( i m p r o v e m e n t to categ o r y 5 o r 6), 61 e x p e r i e n c e d a r e d u c t i o n in s p a s m in muscles in t h e face o r j a w ( n o t t h e n e c k ) . This effect was also s e e n in 8 o f 21 p a t i e n t s in g r o u p II. T h i r t y - t w o o f t h e 234 p a t i e n t s r e c e i v e d m o r e t h a n 10 sets of injections. T h e a v e r a g e effect of the first two t r e a t m e n t s has b e e n c o m p a r e d with t h a t o f t h e 11th a n d 12th t r e a t m e n t s in T a b l e 5.
Table 4. Blepharospasm: visual disability before and after treatment. Figures in brackets in group II show cases with atypical blepharospasm Category
Table 3. Hemifacial spasm No. Group I Group II
Male
Female
Right
Left
42
20
22
17
25
31 +3
11
20
12
19
1 2 3 4 5 6
Group I
Group II
Pre
Post
Pre
Post
36 96 52 8 2 0
3 7 11 24 85 64
18 (4) 23 (4) 13 0 0 0
7 4 3 5 22 13
(3) (1) (1) (1) (2)
Table 5. Patients receiving more than 10 sets of injections: n = 34
Visual disabil- Pre-treatment ity category
Average after 1st and 2nd
11th and 12th
1
8
1
1
2 3 4 5 6
15 10 1 0 0
2 3 5 14 9
2 3 10 16 2
Table 6. Side-effects
Immediate Pain, bruising Delayed Minor
Lid oedema, lid malposition (upper lid : 1-2 mm ptosis) (lower lid : retraction, entropion) Mid-facial muscle stiffness, lip droop or biting of gums
Major
Ptosis covering pupil, double vision
Minor side-effects of the injections were common: these were either immediate (pain, bruising at the injection site) or delayed. Delayed minor side-effects could be the result of therapeutic muscle weakening (lid oedema due to the lack of the normal muscle pump) or excessive local paralysis. This can cause lid malposition and spread to the mid-face and upper lip. Visually significant (major) side-effects are due to spread of paralysis to the levator palpebrae superioris or extraocular muscles (particularly the superior rectus) causing ptosis or double vision (see Table 6). Both minor and major side-effects began in the first 7-10 days after treatment, and resolved at a speed inversely proportional to the severity over the ensuing 2 - 6 weeks. None were permanent. The incidence was higher in group I patients, in whom major side-effects occurred in 10%, minor in 60% over the period of treatment, whereas in group II, total side-effects were 11% (all minor).
Hemifacial spasm In group I there was a 75% reduction in abnormal movements lasting for an average of 15 weeks. Of these patients 33% had minor (visually non-significant) side-effects. The same percentage reduction was achieved in group II for an average of 12 weeks with 19% having minor side-effects.
Discussion
These results confirm that botulinum toxin treatment of blepharospasm is highly effective and show that the efficacy is maintained for up to 40 sets of injections. In group I
77% of the patients improved after treatment to minimal or no visual disability (categories 5 or 6) with only 5% remaining in categories 1 and 2, whereas 65% of group II improved to categories 5 and 6 but 20% remained in categories 1 and 2. The 20%, however, included 5 patients from group I who had been transferred to group II for further study of a poor or reduced response to treatment. Group II also contained 8 patients with atypical blepharospasm, 4 of whom did not benefit from the treatment. Such patients are sometimes described as having "levator inhibition" or apraxia of eye opening, but pre-tarsal blepharospasm is a better term, as these patients show the same electrophysiological characteristics as typical cases (J. Blackie and J. S. Etston, unpublished observations). The poor response in pre-tarsal blepharospasm may in part be due to the difficulty of adequately paralysing the orbicularis oculi close to the lid margin, without causing spread to the extraocular muscles and levator, producing visually significant side-effects. However, it is possible that the atypical features reflect a more serious disorder of brain-stem control of blinking, since even with a profound weakness of orbicularis oculi, these patients have difficulty opening the eyes (persistent levator inhibition) and often, spasmodic upward deviation of the eyes when the lids are open (persistent Bell's phenomenom). Some of these patients, however, benefit from facial nerve avulsion [4]. Successful treatment of blepharospasm reduces the associated facial spasms and oromandibular dystonia in nearly 40% of cases. This was not due to spread of muscle paresis in these patients, and the explanation is unclear. In some cases, facial and jaw movements are used purposively (as are, for example, talking, whistling and singing) to facilitate eye opening, and successful treatment reduced the need for such movements. However, photophobia (another common symptom before treatment) is often also lessened, and it is possible that reduced sensory input from the periocular region when blepharospasm is abolished may help to moderate abnormal central movement control mechanisms. It has been claimed that the beneficial effects of botulinum toxin treatment of blepharospasm are not sustained [9]. Although in the 34 patients treated with more than 10 sets of injections a minor fall-off of benefit is evident (68% of cases in categories 5 and 6 after initial treatment, compared with 53% in the long term), these figures are difficult to interpret. After the first treatment, patients will no longer have a dramatic change in visual function with repeated treatments but be maintained at best in status quo, making subjective evaluation more difficult. Moreover, the underlying dystonia remains untreated and may worsen in some cases, thereby reducing the beneficial effects of the treatment. There was no evidence of a fall-off in the production of weakness of the orbicularis oculi, and the practical visual functional benefit was in general maintained. Side-effects were substantially reduced in group II compared with group I: this was due to several factors. The total number of injections used was reduced, and the site of the injections in the orbital orbicularis made spread to the extraocular muscles and levator less likely.
There was no evidence that the revised regime was less effective, but the onset of relief of spasm may be delayed. The results indicate that botulinum toxin injections are the best treatment for idiopathic blepharospasm and do not support the view that the benefit reduces significantly with repeated treatments. They also indicate the heterogeneous nature of the condition. For example, a subgroup with atypical blepharospasm (pre-tarsal blepharospasm) which may be better treated surgically can be identified.
Hemifacial spasm A female preponderance is shown in this series (male: female 1,3:1) and the left side was involved (44) more than the right (29). The condition responds well to treatment and the modification of the regimen in group II reduced the side-effects by nearly half but appeared to shorten the period of relief of symptoms. Botulinum toxin remains the simplest and safest treatment of hemifacial spasm.
Acknowledgement. I thank Mrs. Kay Mills for her hard work in the preparation of this paper.
References 1. Assael M (1967) Hysterical blepharospasm. Dis Nerv Syst 28 : 256-258
2. Auger RG, Pipgras PG, Laws ER, Miller RH (1987) Microvascular decompression of the facial nerve for hemifacial spasm: clinical and electrophysiological observations. Neurology 31: 346-350 3. Berardelli A, Rothwell J, Day BL, Marsden CD (1985) Pathophysiology of blepharospasm and oromandibular dystonia. Brain 108 : 593-608 4. Bird AC, McDonald WI (1975) Essential blepharospasm. Trans Ophthalmol Soc UK 95 : 250-253 5. Elston JS (1988) Botulinum toxin therapy for involuntary facial movement. Eye 2:12-15 6. Elston JS, Russell RWR (1985) Effect of treatment with botulinum toxin on neurogenic blepharospasm. BMJ 290:18571859 7. Elston JS, Marsden CD, Grandas F, Quinn NP (1988) The significance of ophthalmological symptoms in idiopathic blepharospasm. Eye 2 : 435-439 8. Esteban A, Molina-Negro P (1986) Primary hemifacial spasm; a neurophysiological study. J Neurol Neurosurg Psychiatry 49 : 58-63 9. Garland PE, Patrinely JR, Anderson RL (1987) Hemifacial spasm: results of unilateral myectomy. Ophthalmology 94: 288-294 10. Grandas F, Elston JS, Quinn NP, Marsden CD (1988) Blepharospasm: a review of 264 patients. J Neurol Neurosurg Psychiatry 51 : 767-772 11. Leenders KL, Frackowiack RSJ, Quinn NP, Brooks D, Sumner D, Marsden CD (1988) Ipsilateral blepharospasm and contralateral hemidystonia and parkinsonism in a patients with a unilateral rostral brain stem; thalamic lesion. Structural and functional abnormalities studied with CT, M.R.I. and P.E.T. scanning. Mov Disord 1 : 51-58
Journal of
Neurology © Springer-Verlag1992
The management of blepharospasm and hemifacial spasm John S. Elston* National Hospital for Neurology and Neurosurgery, Queen Square, London WCIN 3BG, UK Received November 5, 1990 / Received in revised form March 28, 1991 / Accepted April 22, 1991
Summary. The aetiology of blepharospasm and hemifacial spasm is different, but both produce involuntary eye closure and facial movements which do not respond to systemic drug treatment. The introduction of therapeutic focal muscle weakening with botulinum toxin injections in the early 1980s appeared to offer great promise in the management of these conditions. In this paper the results of botulinum toxin treatment of 234 patients with blepharospasm and 73 patients with hemifacial spasm over a 7-year period have been analysed. Most patients receive sustained benefit from repeated injections whilst side-effects become less frequent. A clinically recognisable subgroup of patients with blepharospasm respond poorly and may be better treated surgically. Key words: Idiopathic blepharospasm - Hemifacial spasm - Botulinum toxin
Introduction Idiopathic blepharospasm - forceful involuntary contraction of the periocular facial muscles - is a chronic disease, primarily affecting patients in the 5th and 6th decades and severely impairing vision in the majority of cases. Driving, reading and even unaccompanied walking are compromised, making work difficult or impossible; recreational activities requiring vision, such as watching television or gardening, are curtailed. Disfiguring periocular spasms often extend into the face, jaw or neck, and restrict social activities [10]. In its early stages the condition is often misdiagnosed and the symptoms excessive blinking and discomfort or grittiness of the eyes - are ascribed to ocular surface disorders, such as eyelid infections or dry eyes. There is evidence that blepharospasm may co-exist with such disorders and possibly be precipitated by them [7]. Alternatively the condition may be ascribed to stress or hysteria. The early symptoms and signs evolve into spasms of eye closure, * Present address and address for offprbzt requests: The Eye Hospital, Radcliffe Infirmary, Woodstock Road, Oxford OX2 6HE, UK
but even in established cases, because of unpredictable variations in severity, and the absence of a demonstrable cause some doctors still regard the condition as primarily psychiatric or hysterical [1]. There is, however, considerable evidence for an organic aetiology. For example, the clinical spectrum of the disorder may range from isolated periocular spasms to include associated oromandibular or neck spasms (including spasmodic torticollis) or a generalized movement disorder, such as torsion dystonia. Typical blepharospasm has also been described as part of neuroradiologically proven secondary dystonia [11]. However, systemic drug treatment to correct a presumed central neurochemical imbalance is largely unsuccessful. Surgical treatment, either facial nerve avulsion or orbicularis oculi excision may be successful but at a considerable cosmetic and functional cost to the patient. The first reports of a simple safe and effective local treatment for blepharospasm - focal orbicularis oculi denervation with botulinum toxin injections - were therefore of considerable importance, principally because of the relief afforded to patients [6]. Also, the reports have widely publicised the condition and led to increased awareness, more accurate diagnosis and more sympathetic management and appropriate referral amongst the medical profession. At specialist centres the opportunity to study large numbers of patients has provided further clinical and electrophysiological evidence for an organic aetiology for blepharospasm [3]. Hemifacial spasm consists of intermittent synchronous contraction of ipsilateral seventh cranial nerve innervated muscles. Typically the spasms begin in the orbicularis oculi in patients aged in their 40s and 50s and spread to the brow, mid and lower face and neck (platysma) over several years. Spasms are often worse when the patient is anxious, but unless vision is poor in the contralateral eye they do not interfere with work or other activities [8]. However, hemifacial spasm is intractable and a considerable social embarrassment. There is some evidence that microvascular compression of the seventh nerve in its root exit zone in the posterior fossa may be responsible and surgical decompression may be curative [2]. Systemic drug treatment is
largely ineffective, but botulinum toxin injections have p r o v e d to b e h e l p f u l a n d well t o l e r a t e d . This p a p e r d r a w s o n e x p e r i e n c e o f b o t u l i n u m t o x i n treatment of idiopathic blepharospasm and hemifacial s p a s m f r o m 1983 to 1990 a n d a t t e m p t s to d e f i n e its r o l e in t h e l o n g - t e r m m a n a g e m e n t o f t h e s e p a t i e n t s a n d to e x a m i n e w h e t h e r t h e e a r l y p r o m i s e has b e e n fulfilled.
Patients, materials and methods A total of 307 patients have been treated, 234 with blepharospasm and 73 with hemifacial spasm. Of the 234 patients with blepharospasm, 194 (group I) were treated at one centre and have been previously reported [5]. Fourteen of these patients, and 40 new cases (group II) have been treated at another centre. The longest followup period is 7 years (40 sets of injections), the shortest 6 months (2 sets of injections). The patients were classified as having blepharospasm alone or in association with spasms in the mid and lower face, jaw (ormandibular dystonia), neck or elsewhere (blepharospasm plus). Eighteen patients in group I and 3 in group II had a generalized movement disorder. The patients' practical visual function was assessed by the examiner using clinical observation and the results of a standard questionnaire and then graded from 1 to 6 (see Table 2). Category 1 indicates that the patients' eyes are shut all the time; in category 2, the eyes cannot be opened out of doors, but open intermittently indoors. Category 3 patients can open their eyes for periods that enable them to be independent of other people out of doors, and in category 4 this independence extends to being able to continue work but not drive a car or use the eyes recreationally (e.g. reading, watching television). These
activities would be possible, but not for long periods or comfortably in category 5, whilst category 6 is normal. The categorization was agreed with the patient before treatment and at every clinic afterwards, taking the average functional result over the intervening period. The effect of the treatment on the spasm distant from the site of injection in blepharospasm plus was evaluated. In group II patients were designated before treatment as having typical or atypical blepharospasm. Typical was defined as forceful bilateral spasms of eye closure, the muscles involved including the orbital orbicularis oculi with lowering of the brows during spasms. In atypical cases, the eyes were shut but clinically obvious forceful contraction was absent, except when the observer tried to open the eyes. Orbital orbicularis spasm was absent, and the brows were often elevated with the patients complaining of difficulty initiating opening of the eyes (8 cases). The results of treatment of 42 out of the 73 patients with hemifacial spasm (group I) have been published [5]. Three of these patients, and 31 new cases have been assessed and treated (see Table 3). The percentage reduction in abnormal movements and duration of response was measured as before. Patients in group I (both blepharospasm and hemifacial spasm) were treated as previously described [5]. In group II, the number of injections was reduced from 4 to 3, omitting the medial lower lid injection, and the treatment was given further from the lid margin into the orbital orbicularis oculi. However, a l n g dose in 0.2 ml sterile saline was given at each injection site, and the total dosage was therefore the same. (Botulinum toxin courtesy of Dr. Peter Hambleton, Centre for Applied Microbiological Research, Public Health Laboratory Service, Porton Down, UK). For second and subsequent treatments, 0.5ng in 0.1 ml saline was injected as required.
Results Table 1. Blepharospasm No.
Group I Group II
Male
Female
Onset age (average)
Blepharospasm Alone Plus
194
70
124
60.6
38
156
40 + 14
10
30
55.5
19
21
Table 2. Blepharospasm: grading of functional status Category
Visual function
1 2 3 4 5 6
Blind Dependent outside home Independent: poor function Independent: moderate function Inconvenienced Normal
Blepharospasm T h e visual d i s a b i l i t y score b e f o r e t r e a t m e n t a n d o n average after t r e a t m e n t a r e r e c o r d e d in T a b l e 4. T h e figures in b r a c k e t s in g r o u p I I s h o w cases of a t y p i c a l b l e p h a r o spasm. O f 156 p a t i e n t s in g r o u p I with b l e p h a r o s p a s m plus, a n d a g o o d r e s p o n s e to t r e a t m e n t ( i m p r o v e m e n t to categ o r y 5 o r 6), 61 e x p e r i e n c e d a r e d u c t i o n in s p a s m in muscles in t h e face o r j a w ( n o t t h e n e c k ) . This effect was also s e e n in 8 o f 21 p a t i e n t s in g r o u p II. T h i r t y - t w o o f t h e 234 p a t i e n t s r e c e i v e d m o r e t h a n 10 sets of injections. T h e a v e r a g e effect of the first two t r e a t m e n t s has b e e n c o m p a r e d with t h a t o f t h e 11th a n d 12th t r e a t m e n t s in T a b l e 5.
Table 4. Blepharospasm: visual disability before and after treatment. Figures in brackets in group II show cases with atypical blepharospasm Category
Table 3. Hemifacial spasm No. Group I Group II
Male
Female
Right
Left
42
20
22
17
25
31 +3
11
20
12
19
1 2 3 4 5 6
Group I
Group II
Pre
Post
Pre
Post
36 96 52 8 2 0
3 7 11 24 85 64
18 (4) 23 (4) 13 0 0 0
7 4 3 5 22 13
(3) (1) (1) (1) (2)
Table 5. Patients receiving more than 10 sets of injections: n = 34
Visual disabil- Pre-treatment ity category
Average after 1st and 2nd
11th and 12th
1
8
1
1
2 3 4 5 6
15 10 1 0 0
2 3 5 14 9
2 3 10 16 2
Table 6. Side-effects
Immediate Pain, bruising Delayed Minor
Lid oedema, lid malposition (upper lid : 1-2 mm ptosis) (lower lid : retraction, entropion) Mid-facial muscle stiffness, lip droop or biting of gums
Major
Ptosis covering pupil, double vision
Minor side-effects of the injections were common: these were either immediate (pain, bruising at the injection site) or delayed. Delayed minor side-effects could be the result of therapeutic muscle weakening (lid oedema due to the lack of the normal muscle pump) or excessive local paralysis. This can cause lid malposition and spread to the mid-face and upper lip. Visually significant (major) side-effects are due to spread of paralysis to the levator palpebrae superioris or extraocular muscles (particularly the superior rectus) causing ptosis or double vision (see Table 6). Both minor and major side-effects began in the first 7-10 days after treatment, and resolved at a speed inversely proportional to the severity over the ensuing 2 - 6 weeks. None were permanent. The incidence was higher in group I patients, in whom major side-effects occurred in 10%, minor in 60% over the period of treatment, whereas in group II, total side-effects were 11% (all minor).
Hemifacial spasm In group I there was a 75% reduction in abnormal movements lasting for an average of 15 weeks. Of these patients 33% had minor (visually non-significant) side-effects. The same percentage reduction was achieved in group II for an average of 12 weeks with 19% having minor side-effects.
Discussion
These results confirm that botulinum toxin treatment of blepharospasm is highly effective and show that the efficacy is maintained for up to 40 sets of injections. In group I
77% of the patients improved after treatment to minimal or no visual disability (categories 5 or 6) with only 5% remaining in categories 1 and 2, whereas 65% of group II improved to categories 5 and 6 but 20% remained in categories 1 and 2. The 20%, however, included 5 patients from group I who had been transferred to group II for further study of a poor or reduced response to treatment. Group II also contained 8 patients with atypical blepharospasm, 4 of whom did not benefit from the treatment. Such patients are sometimes described as having "levator inhibition" or apraxia of eye opening, but pre-tarsal blepharospasm is a better term, as these patients show the same electrophysiological characteristics as typical cases (J. Blackie and J. S. Etston, unpublished observations). The poor response in pre-tarsal blepharospasm may in part be due to the difficulty of adequately paralysing the orbicularis oculi close to the lid margin, without causing spread to the extraocular muscles and levator, producing visually significant side-effects. However, it is possible that the atypical features reflect a more serious disorder of brain-stem control of blinking, since even with a profound weakness of orbicularis oculi, these patients have difficulty opening the eyes (persistent levator inhibition) and often, spasmodic upward deviation of the eyes when the lids are open (persistent Bell's phenomenom). Some of these patients, however, benefit from facial nerve avulsion [4]. Successful treatment of blepharospasm reduces the associated facial spasms and oromandibular dystonia in nearly 40% of cases. This was not due to spread of muscle paresis in these patients, and the explanation is unclear. In some cases, facial and jaw movements are used purposively (as are, for example, talking, whistling and singing) to facilitate eye opening, and successful treatment reduced the need for such movements. However, photophobia (another common symptom before treatment) is often also lessened, and it is possible that reduced sensory input from the periocular region when blepharospasm is abolished may help to moderate abnormal central movement control mechanisms. It has been claimed that the beneficial effects of botulinum toxin treatment of blepharospasm are not sustained [9]. Although in the 34 patients treated with more than 10 sets of injections a minor fall-off of benefit is evident (68% of cases in categories 5 and 6 after initial treatment, compared with 53% in the long term), these figures are difficult to interpret. After the first treatment, patients will no longer have a dramatic change in visual function with repeated treatments but be maintained at best in status quo, making subjective evaluation more difficult. Moreover, the underlying dystonia remains untreated and may worsen in some cases, thereby reducing the beneficial effects of the treatment. There was no evidence of a fall-off in the production of weakness of the orbicularis oculi, and the practical visual functional benefit was in general maintained. Side-effects were substantially reduced in group II compared with group I: this was due to several factors. The total number of injections used was reduced, and the site of the injections in the orbital orbicularis made spread to the extraocular muscles and levator less likely.
There was no evidence that the revised regime was less effective, but the onset of relief of spasm may be delayed. The results indicate that botulinum toxin injections are the best treatment for idiopathic blepharospasm and do not support the view that the benefit reduces significantly with repeated treatments. They also indicate the heterogeneous nature of the condition. For example, a subgroup with atypical blepharospasm (pre-tarsal blepharospasm) which may be better treated surgically can be identified.
Hemifacial spasm A female preponderance is shown in this series (male: female 1,3:1) and the left side was involved (44) more than the right (29). The condition responds well to treatment and the modification of the regimen in group II reduced the side-effects by nearly half but appeared to shorten the period of relief of symptoms. Botulinum toxin remains the simplest and safest treatment of hemifacial spasm.
Acknowledgement. I thank Mrs. Kay Mills for her hard work in the preparation of this paper.
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