Botulinum toxin therapy of hemifacial spasm: comparing different therapeutic preparations

Hemifacial spasm (HFS) is characterized by involuntary irregular clonic or tonic movements of the muscles innervated by cranial nerve VII on one side of the face, and is most often a result of vascular compression of the facial nerve at the root exit zone (Muscle and Nerve 1998; 21 :1740). Disability associated with this disorder ranges from social embarrassment to interference with vision resulting from involuntary eye closure. Treatment of HFS most often involves botulinum toxin injections, but may also include medications and surgery. We describe treatment with the three types of botulinum toxin currently commercially available – Botox®, Dysport® and Myobloc®/NeuroBloc®.     

Hemifacial spasm: clinical characteristics of 321 Indian patients

Hemifacial spasm (HFS) is a common neurological disorder characterized by involuntary tonic and clonic contractions of the muscles innervated by the facial nerve. We aimed to describe clinical features, common antecedents, triggers and relieving factors in patients with hemifacial spasm to study the correlation of hypertension and HFS, and to compare clinical features of primary and secondary cases of HFS. The data for the study were collected prospectively on a predesigned and pre-tested format at the first attendance in all consecutive HFS patients attending the movement disorders clinic of a tertiary teaching hospital in India. The demographic profile, HFS symptoms, antecedent illnesses and neurological examination were recorded and analyzed. Muscle power in individual muscles innervated by the facial nerve was tested carefully before botulinum toxin injection. Hemifacial spasm occurred in 7.14% (n = 582) of 8,151 cases registered at the movement disorders clinic from 1993 to 2010. Data of 321 patients were complete and were included in the study. Females constituted 49.22% (n = 158). The mean age the patients was 46.02 ± 11.82 years; ipsilateral ear clicking was observed in 22.74% cases. The most common aggravating factor was stress (44.86%), while the most common relieving factor was sleep (44.24%). Two hundred fifty-two patients (78.5%) had primary HFS. The severity of spasm correlated significantly with disease duration (p < 0.001) and weakness of facial muscles (p < 0.001). We did not observe any correlation between HFS on the left side and hypertension, as has been reported earlier. This is one of the largest studies of HFS patients and the only one that prospectively assesses patients with HFS clinically on their first visit. Interesting observations of this study are lack of female preponderance, presence of clicking in the ipsilateral ear and facial weakness even prior to botulinum toxin injection.     

Treatment outcome correlates with knowledge of disease in hemifacial spasm

OBJECTIVES: Hemifacial spasm (HFS), a potentially disabling facial condition affects quality of life (QOL) and botulinum toxin is an effective treatment. No studies have examined whether a better level of knowledge of the disease would lead to an improved quality of life and treatment response in HFS. We examined the relationship between knowledge of disease with improvement in QOL following botulinum toxin treatment in HFS patients. PATIENTS AND METHODS: A total of 106 HFS patients (mean age of 56.8+/-9.9 years) were prospectively included. A baseline knowledge questionnaire and a validated disease-specific quality of life scale (HFS-7) were administered before and after botulinum toxin treatment. RESULTS: A better educational level was an independent predictor of high knowledge of HFS (p=0.02). Multivariate analysis using improvement in HFS-7 (total and subscore) as outcomes, and adjusting for age, gender, education, severity and duration of HFS, showed that high knowledge was predictive of a bigger improvement in HFS-7 total (p=0.03) and HFS-7 subscore (p=0.03). CONCLUSIONS: HFS patients with high knowledge of disease reported better improvement in QOL following botulinum toxin treatment. Better educational efforts will augment current medical and surgical treatments in improving QOL in HFS. Our findings could potentially be extended to many other medical conditions.     

Intravenous levetiracetam as treatment for status epilepticus

There are established drugs for the treatment of status epilepticus (SE) but their potentially hazardous side-effects are well known. Levetiracetam (LEV) is a novel anticonvulsant available for intravenous (i.v.) application. It could be an alternative when standard drugs fail or should be avoided. We retrospectively identified patients from two German teaching hospitals who were treated with LEV i.v. for SE. Their charts were reviewed regarding sociodemographic data, type, etiology, onset and duration of SE, dose of LEV, concurrent antiepileptic drugs (AED) treatment, tolerability, and outcome. Thirty-two patients (15 female) were found who were treated with i.v. LEV for SE (median age 71 years). Two patients were exclusively treated with LEV. Eight received a low and further 20 patients a high dose of benzodiazepines before LEV. Two patients were treated with LEV to enable discontinuation of narcosis. SE was generalized convulsive in five, nonconvulsive in 20, and simple focal in seven patients. Etiology was acute 13 times and remote symptomatic 16 times; three SE were of unknown etiology. Therapy was initiated within a median time of 3 h and LEV i.v. was applied within a median time of 6 h. Median LEV bolus was 2,000 mg; median total dose on day 1 was 3,500 mg. Benzodiazepines plus i.v. LEV terminated SE in 23 patients without application of additional anticonvulsants, 10 within 30 min. LEV could not terminate SE in seven patients. We documented nausea and emesis in one and elevation of liver enzymes in another patient that were likely to be attributed to LEV. LEV i.v. seems to be safe with relevant efficiency for the treatment of SE in elderly and multimorbid patients when comorbidity and respiratory insufficiency precludes high doses of benzodiazepines or phenytoin.     

Functional end-plate recovery in long-term botulinum toxin therapy of hemifacial spasm: a nerve conduction study

Botulinum toxin type-A is currently thought to be effective and safe for hemifacial spasm (HFS). The pre-synaptic block of acetylcholine release at the neuromuscular junction induces depression of orbicularis oculi muscle compound motor action potential (CMAP). The aim of our study was to evaluate at what extent end-plate functional recovery is possible even in botulinum toxin treatments lasting up to 15 years. We examined 81 outpatients with primary HFS (mean treatment duration = 7.2 ± 4.2 years) who underwent neurophysiologic study, once clinical effect of the previous treatment had vanished. The mean CMAP amplitude, mean rectified amplitude of response 1 (R1) of the blink reflex and area of response 2 (R2) of treated orbicularis oculi muscle were measured in comparison to the controlateral side. Mean amplitude of the above mentioned parameters was slightly lower (about 20%; p < 0.001) in the treated side at the end of the follow-up period (4.7 ± 1.7 months). The CMAP amplitude reduction weakly correlated with the interval from last treatment, while other neurophysiologic parameters did not change due to treatment duration or total toxin amount. Our study demonstrates that botulinum toxin affects compound motor action potential and blink-reflex responses for at least 4–5 months in HFS patients. The residual block is slight and does not increase with repeated injections after several years of treatment. Our study, beside confirming the long-term efficacy of botulinum toxin treatment for HFS, provides neurophysiologic evidence that therapeutic effect may be obtained without hindering the regenerative potential of the nerve-muscle complex.     

Combination of blepharospasm and apraxia of eyelid opening: a condition resistant to treatment

Blepharospasm is seen in many cases of Parkinsonism including progressive supranuclear palsy. These patients usually respond well to botulinum toxin, however some patients subsequently fail to respond to even higher doses of botulinum toxin after an initial good response. They should not be considered failure of treatment with botulinum toxin, as a significant number of these patients have underlying apraxia of eyelid opening in addition to blepharospasm, which may be the cause of failure to respond to botulinum toxin. Combination of eyelid crutches or myomectomy with botulinum toxin is more effective in these patients as compared to an individual treatment modality. In this report, we present two patients with progressive supranuclear palsy who failed to respond to botulinum toxin because they had underlying apraxia of lid opening. Partial myomectomy in one patient and eyelid crutches in the other in combination with botulinum toxin lead to a much better response to botulinum toxin.     

Treatment of hemifacial spasm with botulinum toxin.

The effectiveness of botulinum toxin injections in 11 patients with hemifacial spasm was investigated in a prospective placebo-controlled blinded study. The patients were treated with four sets of injections to various facial muscles, selected by clinical evaluation. Three injections were with graded doses of toxin and one was with placebo. The order of injections was random and unknown to the patients. Results were scored both subjectively by patient assessment of symptoms and objectively by blinded review of videotapes made one month after each injection. Subjective improvement occurred after 79% of injections with botulinum toxin, regardless of dose of toxin. Only 1 patient improved after placebo. Objective improvement was seen after 84% of injections with botulinum toxin. No patient showed objective improvement after placebo injection. The most frequent side effect was facial weakness, seen after 97% of injections of botulinum toxin. Facial bruising (20%), diplopia (13%), ptosis (7%), and various other mild side effects were seen less frequently. Botulinum toxin appears to be an effective and safe method of therapy for hemifacial spasm.     

Gabapentin as treatment for hemifacial spasm.

Hemifacial spasm, a life-long condition characterized by involuntary unilateral contractions of the facial muscles, is a disabling disorder often resulting in patient irritation and social embarassment. Its probable etiology is neurovascular compression of the facial nerve at its root exit zone. The current medical treatment consists of either baclofen or anticonvulsant drugs, with limitation due to side effects or low efficacy. In recent years botulinum toxin injection and microvascular decompression of the facial nerve have been shown to be highly successful. However, both procedures share some complications and require special techniques. We present 5 patients affected by hemifacial spasm who responded well to the novel anticonvulsant drug gabapentin. Gabapentin was administered at a dose ranging from 900 to 1,600 mg daily, with rapid and clear improvement of spasms and absence of any remarkable adverse effects. Our findings suggest that gabapentin may be an effective treatment for patients with hemifacial spasm with a very good ratio of therapeutic effects to side effects when compared with other drugs currently used.     

Hemifacial spasm: Clinical findings and treatment

Hemifacial spasm (HFS) is a peripherally induced movement disorder characterized by involuntary, unilateral, intermittent, irregular, tonic or clonic contractions of muscles innervated by the ipsilateral facial nerve. We reviewed the clinical features and response to different treatments in 158 patients (61% women) with HFS evaluated at our Movement Disorders Clinic. The mean age at onset was 48.5 ± 14.1 years (range: 15–87) and the mean duration of symptoms was 11.4 ± 8.5 (range: 0.5–53) years. The left side was affected in 56% instances; 5 patients had bilateral HFS. The lower lid was the most common site of the initial involvement followed by cheek and perioral region. Involuntary eye closure which interfered with vision and social embarrassment were the most common complaints. HFS was associated with trigeminal neuralgia in 5.1% of the cases and 5.7% had prior history of Bell's palsy. Although vascular abnormalities, facial nerve injury, and intracranial tumor were responsible for symptoms in some patients, most patients had no apparent etiology. Botulinum toxin type A(BTX-A)injections, used in 110 patients, provided marked to moderate improvement in 95% of patients. Seven of the 25 (28%) patients who had microvascular decompression reported permanent complications and the HFS recurred in 5 (20%). Although occasionally troublesome, HFS is generally a benign disorder that can be treated effectively with either BTX-A or microvascular decompression. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21: 1740–1747, 1998     

A型肉毒毒素治疗面肌痉挛、眼睑痉挛疗效观察

目的观察A型肉毒毒素治疗面肌、眼睑痉挛的疗效。方法采用A型肉毒毒素局部注射治疗偏侧面肌痉挛51例、眼睑痉挛8例,并使用Cohen和Albert量表对疗效进行评估。结果31例(52.5%)症状完全缓解,22例(37.2%)明显改善,6例(10.1%)部分改善,疗效平均持续约9～33周,复发者重复注射仍有效。不良反应可出现眼睑闭合不全、面肌无力、眼睑下垂等共18例,均在4周内恢复。结论局部注射A型肉毒毒素确为一种安全有效的治疗面肌、眼睑痉挛的方法。     

No clinical or neurophysiological evidence of botulinum toxin diffusion to non-injected muscles in patients with hemifacial spasm

Botulinum toxin injected into a muscle may diffuse to nearby muscles thus producing unwanted effects. In patients with hemifacial spasm, we evaluated clinically and neurophysiologically, whether botulinum toxin type A (BoNT-A) diffuses from the injection site (orbicularis oculi) to untreated muscles (orbicularis oris from the affected side and orbicularis oculi and oris from the unaffected side). We studied 38 patients with idiopathic hemifacial spasm. Botulinum toxin was injected into the affected orbicularis oculi muscle alone (at 3 standardized sites) at a clinically effective dose. Patients were studied before (T0) and 3-4 weeks after treatment (T1). We evaluated the clinical effects of botulinum toxin and muscle strength in the affected and unaffected muscles. We also assessed the peak-to-peak amplitude compound muscle action potential (CMAP) recorded from the orbicularis oculi and orbicularis oris muscles on both sides after supramaximal electrical stimulation of the facial nerve at the stylomastoid foramen. In all patients, botulinum toxin treatment reduced muscle spasms in the injected orbicularis oculi muscle and induced no muscle weakness in the other facial muscles. The CMAP amplitude significantly decreased in the injected orbicularis oculi muscle, but remained unchanged in the other facial muscles (orbicularis oris muscle on the affected side and contra-lateral unaffected muscles). In conclusion, in patients with hemifacial spasm, botulinum toxin, at a clinically effective dose, induces no clinical signs of diffusion and does not reduce the CMAP size in the nearby untreated orbicularis oris or contralateral facial muscles.     

Use of botulinum toxin to treat blepharospasm in a 16-year-old with a dystonic syndrome

A 16-year-old boy with generalized dystonia had continuous, severe blepharospasm and facial grimacing. Local intradermal injections of botulinum A toxin greatly reduced the spasms and improved function. No side effects were observed. Local botulinum A toxin injections may be useful in the treatment of eyelid and facial spasms in patients with generalized dystonias.     

Levetiracetam-induced thrombocytopenia among inpatients: a retrospective study

Lately, few case reports have brought forth limited cases of levetiracetam (LEV)-induced thrombocytopenia. To estimate the burden of LEV-induced thrombocytopenia, we reviewed medical records of 758 patients aged 18 years or older who received LEV during their stay at the University Hospital from June 2005 to December 2008. In patients identified with thrombocytopenia, records were reviewed to establish a cause of thrombocytopenia and possible causal role of LEV. Of 758 patients, 29 patients were identified with thrombocytopenia while on LEV therapy. For 23 patients, an alternative cause for thrombocytopenia was established; 4 patients had preexisting thrombocytopenia without any appreciable change in platelet count after addition of LEV. One patient had limited data for identifying the cause of thrombocytopenia. A single patient had clear temporal co-relation and association of thrombocytopenia with LEV therapy. LEV-induced thrombocytopenia is a rare but reversible complication of LEV therapy. The mechanism remains unknown.     

Botulinum toxin treatment of hemifacial spasm and blepharospasm: objective response evaluation.

Twenty seven patients with hemifacial spasm (HFS) and sixteen patients with blepharospasm (BS) having mean Jankovic disability rating scale score of 2.56+0.58 SD and 2.81+0.54 SD, respectively, were treated with botulinum toxin A (BTX-A) injections. The total number of injection sessions were ninety one with relief response in 98.91%. The mean improvement in function scale score was 3.78+0.64 SD and 3.29+1.07 SD respectively, in HFS and BS groups. The clinical benefit induced by botulinum toxin lasted for a mean of 4.46+3.11 SD (range 2 to 13) months in HFS group and 2.66+1.37 SD (range 1 to 6) months, in BS groups. Transient ptosis was seen in 4.39% of total ninety one injection sessions. These findings show that local botulinum toxin treatment provides effective, safe and long lasting relief of spasms.     

Levetiracetam monotherapy for late poststroke seizures in the elderly

Stroke is the most common cause of seizures in the elderly. Antiepileptic drugs are used to treat most patients with late poststroke seizures. The aim of this study was to evaluate the efficacy and tolerability of levetiracetam (LEV) in patients aged 60 or older with late-onset poststroke seizures. This prospective study evaluated patients 60 years of age or older, who had at least two late-onset poststroke seizures and were given LEV monotherapy. Demographic data and seizure and stroke characteristics were recorded. Outpatient visits were made after 2, 4, 6, 9, and 12 months and every 3 months thereafter, and the effectiveness and tolerability of LEV were investigated. Thirty-four patients with a mean age of 69.76+/-6.41 were included in this study. Average seizure frequency before treatment was 3.61+/-3.02/month. Mean follow-up time was 17.68+/-3.24 months. At daily doses of 1000-2000 mg, 82.4% of the patients were seizure free, and 7 patients (20.6%) had side effects. LEV was discontinued in one patient because of severe somnolence. Two patients were switched to another antiepileptic drug because of uncontrolled seizures despite an increase in dose up to 3000 mg/day. LEV monotherapy can be effective and well tolerated in elderly patients with late-onset poststroke seizures.     

Hemifacial spasm non-motor and motor-related symptoms and their response to botulinum toxin therapy

Hemifacial spasm (HFS) is a chronic movement disorder which presents as clonic and/or tonic facial muscle contractions frequently accompanied by many other sensory (visual or auditory disturbances, pain), motor (facial weakness, trismus, bruxism, dysarthria) and/or autonomic (lacrimation, salivation) symptoms. The aim of the study was to assess the occurrence of HFS non-motor and motor-related symptoms and their responsiveness to botulinum toxin type A (BTX-A) therapy. 56 HFS patients were included in the open-label design study. Patients were examined three times: before BTX-A injection, and 2 and 12 weeks later. The occurrence of non-motor and motor-related symptoms was assessed by a special questionnaire, and the severity of HFS was rated by the Clinical Global Impression-Severity scale (CGI-S) and depression symptoms by the Beck Depression Inventory (BDI). Over 81% of the patients before BTX-A therapy reported HFS non-motor and motor-related symptoms. Almost 50% of the patients reported more than three symptoms. The most frequent symptoms were: tearing (44.5%), eye irritation (39.3%), facial paraesthesia (26.8%) and hearing of a “clicking” sound (25.0%). 2 weeks after BTX-A injection 75% of the patients did not report any symptoms and 20% reported only one or two. 3 months later the number of symptoms had increased again, with 57% of patients reporting at least one. The number of HFS non-motor and other symptoms did not correlate with the patients’ age, disease duration and the presence of neuro-vascular conflict, but were positively correlated with the CGI-S and BDI scores. This study showed that muscle contractions in HFS patients are commonly accompanied by non-motor and other motor-related symptoms and most of them are reduced following BTX-A treatment.     

Blefarospasmo y espasmo hemifacial: tratamiento a largo plazo con toxina botulínica

Introduction

Our purpose is to describe the demographic, clinical and therapeutic characteristics of patients with blepharospasm (BS) and hemifacial spasm (HFS) in treatment with botulinum toxin type A (BtA).

Patients and methods

Retrospective analysis of patients diagnosed with BS or HFS and treated with BtA in the Neurology Department at Complejo Asistencial de Segovia between March 1991 and December 2009.

Results

Different variables were collected from 34 patients with BS and 55 with HFS, of whom 44.1% and 32.7% respectively had been undergoing treatment with BtA for more than 10 years. Elapsed time from symptom onset to the first visit was 24 months in the BS group and 59.7 months in the HFS group. Diagnosis was given on the first visit for 76.5% of the BS patients and 90.7% of the HFS patients. Patients were referred by their primary care centres in 34.6% of the cases with BS and in 77.6% of the cases with HFS. The most commonly used BtA preparation was BOTOX^® in both groups, and there were no cases of primary or secondary resistance. The median dose of BtA was raised gradually in both groups, and the increase was statistically significant during the early years of treatment. The most common side effect was ptosis (47.1% in BS, 32.5% in HFS).

Conclusions

BS and HFS are the most common facial movement disorders. The demographic and clinical characteristics and therapeutic findings from this study show that treatment with BtA is both effective and safe over the long term.     

The use of botulinum toxin type-B in the treatment of patients who have become unresponsive to botulinum toxin type-A -- initial experiences.

The increasing use of botulinum toxin type-A, especially for focal dystonia and spasticity has highlighted the issue of secondary non-responsiveness. Within the last few years botulinum toxin type-B (Myobloc/Neurobloc) has become commercially available as an alternative to type-A. This paper discusses our initial experience of botulinum toxin type-B in a total of 63 individuals who attended our botulinum clinic. Thirty-six patients had cervical dystonia and a secondary non-response to type-A toxin. Thirteen of these patients (36%) had a reasonable clinical response to Neurobloc and continue to have injections. The other 23 patients either had no response, or a poor response, or had unacceptable side effects and ceased treatment. A small number of people with blepharospasm, hemifacial spasm and foot dystonia also had a disappointing response to injection. Twenty patients with spasticity were also type-A resistant. Seven of these show some continuing response to type-B, without unacceptable side effects. These findings demonstrate that botulinum toxin type-B has a place in the management of patients who have become non-responsive to type-A, but overall the responses to type-B toxin were disappointing.     

Young onset hemifacial spasm

INTRODUCTION: Hemifacial spasm (HFS) frequently affects middle aged individuals and the clinical features and etiology have been well reported. However, there is limited data on the exact pathogenesis in young-onset HFS. If age is a major determinant of the etiology or influences the presentation of HFS, there may be clinical differences between the young and elderly HFS patients. OBJECTIVES: We determined the prevalence, clinical and imaging features of young-onset HFS (age of onsetor=65 years) HFS patients. METHODS: We examined consecutive patients clinically diagnosed with HFS in a tertiary referral center. The clinical (demographics, clinical presentation, severity of HFS, associated medical conditions and other variables) and imaging findings of young onset patients and old onset patients were tabulated and compared. RESULTS: Amongst 230 consecutive HFS patients, 15 (6.5%) were young-onset HFS and 50 (21.7%) were old-onset HFS. In the young-onset HFS, the mean age of onset of symptoms was 26.5+/-6.5 (6-30) years, with 80% women and 75.0% of young onset HFS having neurovascular compression (NVC) of the root exit zone (REZ) of the facial nerve on the ipsilateral side; 86.7% had initial onset of twitching in the upper eyelids that later progressed to the lower facial muscles. While the prevalence of hypertension, diabetes mellitus and other associated vascular disorders in late onset HFS was higher than in young onset groups, the clinical features and frequency of NVC of the facial REZ between the two groups were similar. CONCLUSIONS: We demonstrated a 6.5% frequency of young-onset HFS in our cohort of HFS and their clinical presentation was similar to the old onset patients. Genetic, anatomic or other unidentified factors may contribute to NVC in young-onset HFS.     

Treatment with botulinum toxin improves the hyperexcitability of the facial motoneuron in patients with hemifacial spasm

Abstract

Botulinum toxin type A (BTX) injection into the orbicularis oculi muscle is an effective treatment for patients with hemifacial spasm (HFS). The objectives of this study were to investigate the effect of this treatment on HFS, in particular the associated hyperexcitability of the facial motor nucleus, and to discuss the potential mechanism of HFS. F waves in the mentalis muscle were examined before, 2 and 6 weeks after the BTX treatment of only the orbicularis oculi muscle in ten patients with HFS. F/M ratio, duration of F waves and frequency of F waves decreased significantly after the BTX treatment compared with those before the BTX treatment. These findings demonstrate that the excitability of the facial motonucleus decreases after BTX treatment of the orbicularis oculi muscle. From these results, we hypothesize that the trigeminal afferent input and the cortical control contribute to the hyperexcitability of the facial motor nucleus in patients with HFS. This warrants further investigation into the pathophysiology of HFS.