Efficacy and Safety of Long-term Botulinum Toxin Treatment in Craniocervical Dystonia: A Systematic Review

Botulinum neurotoxins have been shown to be a safe and effective therapeutic option for most forms of focal dystonia, and are now considered to provide the best symptomatic treatment in these disorders. However, only a few papers addressed the long-term efficacy and safety of repeated treatments with this drug. This article reviews the data from clinical trials that have assessed the long-term results of botulinum neurotoxin type A (BoNT-A) and type B in the treatment of the different forms of focal craniocervical dystonia, cervical dystonia (CD), blepharospasm, oromandibular, and laryngeal dystonia. Studies on the long-term effects of BoNT-A therapy have demonstrated that the majority of patients comply with this repeated treatment because they experience a positive and stable effect over time. It is still unclear whether in patients with focal dystonia the mean dose of BoNT-A changes over time. In spite of the wide spectrum of side effects reported to be associated with BoNT-A treatment, there is no evidence of specific side effects due exclusively to the long-term use of such drugs. The only exception to these positive long-term findings is the occurrence of a subgroup of patients with CD who fail to maintain a sustained response after the first or second effective treatment, partly owing to the development of neutralizing antibodies against the toxin. Longitudinal studies aimed at defining the risk factors for this abnormal pattern of response to botulinum toxin treatment are currently being conducted.     

A comparative crossover study on the treatment of hemifacial spasm and blepharospasm: preseptal and pretarsal botulinum toxin injection techniques

Hemifacial spasm (HFS) and benign essential blepharospasm (BEB) are chronic and disabling abnormal craniofacial movements that produce involuntary eyelid twitching and closure. The efficacy and safety of botulinum toxin type A (BoNT-A) injections have been accepted and widely used for the treatment of HFS and BEB. However, different injection sites may influence the effectiveness, doses, and side effects. The aim of this study is to compare the efficacy, patient satisfaction, and complications of low-dose BoNT-A injections between injection at the preseptal (PS) and the pretarsal (PT) portion of the orbicularis oculi muscle. A total of 40 patients, 31 patients with HFS and 9 patients with BEB, participated in this study. Each patient received both PS and PT BoNT-A injections in a crossover design study. Latency to response, duration of improvement, the Jankovic Rating Scale (JRS), self-response scale, patient satisfaction scale, and complications were compared. Low-dose injections of BoNT-A at the PT portion produced a significantly higher response rate in terms of latency to response, duration of improvement, JRS, self-response scale, and patient satisfaction scale than the PS injections. Major side effects including ptosis and droopy eyelid were observed only after the PS injections. These findings confirmed that low-dose injections of BoNT-A at the PT portion provide more efficacy, patient satisfaction, and fewer complications than the PS injections for the treatment of involuntary eyelid twitching and closure in patients with HFS and BEB.     

Efficacy and safety of repeated doses of botulinum toxin type B in type A resistant and responsive cervical dystonia.

Efficacy of botulinum toxin type B (BoNT B) for the treatment of type A-resistant (AR) and non-A-resistant (NAR) cervical dystonia (CD) has been demonstrated in several single injection studies. There is little data available on long-term therapy with repeated injection sessions and it is unknown if AR and NAR patients respond in a similar manner over time. To evaluate the long-term efficacy and safety of BoNT B in AR and NAR CD patients, we carried out a prospective, open-label study examining 10 repeated dosing sessions of BoNT B in 34 patients with CD (15 AR and 19 NAR). Dosing was started at 10,000 units and could be increased to 25,000. Assessments included the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and a patient global assessment at each baseline (injection) and Week 4 (peak effect) visit. Change in TWSTRS total was the primary efficacy end point. Data was analyzed using repeated-measures analysis of variance. BoNT B therapy resulted in an overall significant improvement of CD (P<0.001) and improvement was seen in all 10 individual sessions (2.5 years). The magnitude of response decayed over time (P<0.001). There was no difference between AR and NAR patients with regard to dose, treatment effect, or decay in response. The AR group perceived (patient global) treatment as being less effective (P=0.047). Dry mouth frequency decreased with each session despite increasing doses whereas flu-like syndrome and weakness increased. BoNT B therapy provides long-term benefit for CD patients but the magnitude of response diminishes over time. The cause of this decay is probably multifactorial. AR and NAR CD patients respond in a similar fashion.     

Long-term effects of botulinum toxin A in children with cerebral palsy

The long-term effects of botulinum toxin A (BoNT-A) treatment in children with cerebral palsy (CP) are still elusive. We studied a prospective clinical cohort of 94 children with different subtypes (50% spastic diplegic CP, 22% hemiplegic CP, 25% tetraplegic CP, 3% dyskinetic CP), sex (55% male, 45% female), severity according to Gross Motor Function Classification System (29% Level I, 15% Level II, 16% Level III, 17% Level IV, 23% Level V), and age (median 5y 4mo, range 11mo–17y 8mo). The longest follow-up time was 3 years 7 months (median 1y 6mo) and included a maximum of eight injections per muscle (median two injections to a specific muscle). Outcome measurements were muscle tone (Modified Ashworth Scale) and joint range of motion (ROM). Assessments were made at a minimum before and 3 months after each injection. Ninety-five per cent confidence intervals for differences from baseline were used to identify significant changes. BoNT-A injections induced reduction of long-term spasticity in all muscle-groups examined: the gastrocnemius, hamstring, and adductor muscles. The reduction in tone was most distinct in the gastrocnemius muscle, and each repeated injection produced an immediate reduction in muscle tone. However, improvement in ROM was brief and measured only after the first injections, whereupon the ROM declined. Thus, the results suggest that BoNT-A can be effective in reducing muscle tone over a longer period, but not in preventing development of contractures in spastic muscles. The dissociation between the effects on muscle tone and ROM indicates that development of contractures is not coupled to increased muscle tone only, but might be caused by other mechanisms.     

Experience with long-term treatment with albumin-supplemented botulinum toxin type A

In earlier studies, we have demonstrated the efficacy of albumin-supplemented botulinum toxin type A (ASBTA) in principle. Here, we present long-term data from 106 patients who received ASTBA over 5–10 years for the treatment of cervical dystonia, blepharospasm and hemifacial spasm. Vials of Dysport^® were diluted in 0.1% albumin solution to a concentration of 25 units/ml. Overall patients and indications, the mean latency to response was 7.1 ± 2.2 days, the mean duration of response was 12.3 ± 3.1 weeks and the mean global clinical improvement (scale 0–3) was 2.6 ± 0.2. Only one patient had neutralizing antibodies against BoNT-A. Side effects were less frequent than known for conventional BoNT-A and generally mild. These findings were confirmed by analysis of data of 71 patients who have been reconverted from ASBTA to conventional dilutions of Dysport^® or Botox^®. We conclude that long-term treatment with ASBTA is effective, safe and help to reduce costs.     

Evidence based medicine in the use of botulinum toxin for back pain

Summary Two randomized, prospective studies, one double blind and one open label, longterm evaluated efficacy and safety of Botulinum toxin A (Allergan-Inc) in 31 and 75 patients with chronic low back pain. Both studies used a novel technique imploying 5 level (L1 to L5) injections (40–50 units/level) of BoNT-A into erector spinae muscles. Significant (p < 0.05) improvement of pain intensity, frequency and activities of daily living was noted in 60% and 53% of the patients, respectively. The second study also depicted safety with repeated injections over 14 months of follow up. Botulinum toxin-A should be considered for treatment of low back pain when other modes of treatment fail to improve pain. Correspondence: Bahman Jabbari, Department of Neurology, Yale University School of Medicine, LCI 708, 15 York Street, New Haven, CT 06520, USA     

Current status of antidepressants: clinical pharmacology and therapy

Effective antidepressants, including imipramine and monoamine oxidase (MAO) inhibitors, were discovered serendipitously in the 1950s. Many additional agents have been introduced since then, but most are chemically or pharmacologically similar to those known for nearly four decades. Some recently introduced antidepressants offer either lesser or dissimilar side effects, but none exceeds older treatments in efficacy. Selective serotoninpotentiating agents and short-acting MAO-A inhibitors promise efficacy with greater safety. Progress is made difficult because atypical or treatment-resistant patients are more often available for study than typical patients, and because most studies must rely heavily on potentially misleading "standard drug versus new drug" comparisons. Rational development of novel or better agents is slow, in part, due to limited understanding of the biological basis of major affective disorders and some circularity in relating actions of known drugs to pathophysiologic hypotheses. Action mechanisms of antidepressants are subtle and complex: adaptive changes occur in brain monoaminergic neurotransmission following repeated administration of agents of the tricyclic antidepressant (TCA) type that may lead to net facilitation of alpha 1-adrenergic transmission. Important advances have been made in using plasma TCA levels to guide individualization of dosing, in exploring higher doses of antidepressants when ordinary doses prove ineffective, and in recognizing a broadening spectrum of possible indications for antidepressants in adults and children. These indications include panic disorder, obsessive compulsive disorder, attention deficit disorder, and bulimia. Evidence for the prophylactic effects of antidepressants after the first months following recovery from an index episode of major depression is weak, and the treatment of common recurrent or chronic depression remains unsatisfactory. Gains have been made in increasing clinicians' and the general public's awareness of the common occurrence and appropriate treatment of major depression, even when the depression is associated with other medical or psychiatric disorders.     

Botulinum-Neurotoxin in der Behandlung der Spastizit?t im Erwachsenenalter

Spasticity is one of the major causes of functional impairment in adults with lesions of the central nervous system. For instance, approximately 30% of post-stroke patients suffer from different degrees of spasticity with possible consecutive impairments. Numerous studies or meta-analyses showed that local injections of botulinum toxin in spastic muscles lead to dose-dependent reduction in muscle tone and improvement of passive movements (e. g. facilitated care), especially following repeated injections.However, country-specific regulations and patient-remote administration in German health care often do not allow adequate provision of this therapy. Thus, the present consensus statement based on the EBM analyses of the published international literature tries to highlight recent advances and the standard in the field of local spasticity treatment, aiming to facilitate communication between the decision makers and German reimbursement institutions in health care. Prior to initiation of BoNT-A injections, patient-oriented goals should be identified in a multiprofessional context to assure realistic goals for this specific treatment and patient expectations. In Germany for the treatment of focal spasticity following stroke three products have been approved: Botox? (Pharm Allergan, Ettlingen), Dysport? (Ipsen Pharma, Ettlingen) and Xeomin? (Merz Pharma, Frankfurt/Main). For all preparations safety has been repeatedly shown. Functional improvements have also been illustrated for selected patients concerning hand/arm function and gait. The dose per muscle and the selection of muscles to be injected have to be individualized according to the patient's symptoms and should be accompanied by modern neurorehabilitative therapies such as redression or repetitive activation of the injected and antagonistic muscles.     

Treatment of spasmodic torticollis with local injections of botulinum toxin

Summary Thirty-seven patients with spasmodic torticollis (cervical dystonia) who received repeated local injections of botulinum toxin have been followed up for a mean period of 12.3 (10–29) months, during which time 138 treatment sessions were performed. Mean doses per muscle averaged 320 mouse units (mu; range 160–1000 mu botulinum toxin A prepared by CAMR, Porton Down, UK). Eighty-six per cent of patients experienced significant improvement of posture and 84% of those with pain had relief following the first injection. Muscular patterns of recurrent torticollis were relatively constant and in most patients efficacy was maintained with subsequent injections, while 15% of all follow-up sessions failed. Only 2 of 37 patients were consistent non-responders; 22% and 10% of all sessions were complicated by transient dysphagia and weakness of neck muscles, respectively. It is concluded that local botulinum toxin injections can be a safe and efficaceous long-term treatment of spasmodic torticollis and that optimal doses should be between 200 and 400 mu/muscle.     

Practical prescribing and long-term efficacy and safety of zonisamide

Long-term efficacy, tolerability and safety of antiepileptic drug (AED) therapy is essential given the chronic nature of epilepsy. Zonisamide (Zonegran), a novel AED with a broad range of mechanisms of action contributing to its antiseizure efficacy, has been evaluated extensively for the long-term management of epilepsy. Open-label extension studies in the United States and Europe suggest continued efficacy of zonisamide in long-term treatment without development of adverse events further to those seen in registration studies. Baseline seizure frequency is reduced by approximately 40-70% during long-term treatment for up to 2 years, and 30-50% of patients attain >or=50% reduction in seizure frequency across all categories of seizure and durations of treatment. Preliminary data indicate a progressive decline in seizure frequency with continued zonisamide treatment. Zonisamide is well tolerated in long-term use, with a trend towards decreasing incidence of generally mild adverse events over time and a low rate of withdrawal during chronic use. Nephrolithiasis and other serious adverse events are infrequent, and can be minimised by appropriate management and patient education. This profile of maintained efficacy, tolerability and safety during sustained administration in combination with other AEDs supports zonisamide as a valuable adjunctive agent in the long-term management of refractory partial epilepsy.     

Botulinum toxin type A treatment in neurogenetic syndromes

Purpose: To review the use of therapeutic botulinum toxin type A (BoNT-A) treatments in uncommon neurogenetic syndromes.

Method: A retrospective questionnaire and interview study of a selected case series to assess the efficacy and safety following initial BoNT-A treatment (50–400 units per subject) was conducted to determine the response of families to treatment. Twelve male and six female subjects with ages from 2–19 years were included. The reasons for treatments were based on both patient-related and caregiver-related objectives. Satisfaction with achievement of stated goals was assessed by follow-up interviews.

Results: Beneficial effects were reported in 56%, some effects in 22% and no to minimal effects in 22%. The duration of effect ranged from 10 days to 12 months with an average of 3.16 months. Ten families would repeat the injections as needed, four would not and four were not sure. Unanticipated effects of BoNT-A treatments were reported by some families. Adverse effects did not occur with the doses that were used.

Conclusions: The results suggest that obtaining family input may be useful when treating spasticity in unusual circumstances. The use of BTX-A in uncommon neurogenetic syndromes was supported by the majority of families interviewed.     

The broadening application of chemodenervation in X-linked dystonia-parkinsonism (Part II): an open-label experience with botulinum toxin-A (Dysport®) injections for oromandibular, lingual, and truncal-axial dystonias

While the majority of chemodenervation clinics worldwide typically use botulinum toxins for the treatment of common conditions such as blepharopsams, cervical dystonia, limb dystonia, and spasticity, the unusually high concentration of X-linked dystonia-parkinsonism (XDP) has allowed us to collect and describe our experience in the use of botulinum toxin type A (BoNT-A) on rarer dystonic patterns. BoNT-A (Dysport?) was injected in a total 109 dystonias of XDP. Our cohort included: 50 cases in the oromandibular area (jaw opening: 32 cases, jaw closing: 12 cases, and jaw deviation: 6 cases); 35 cases in the lingual area (tongue protrusion: 27 cases and tongue curling: 8 cases); and, 24 cases in the truncal-axial area (flexor: 12 cases, extensor: 7 cases, and lateral-extensor: 5 cases). Interestingly, pain, often a nonprominent symptom of dystonias, was frequently reported in 40/50 XDP cases with oromandibular dystonia and 18/24 XDP cases with truncal-axial dystonia. All BoNT-A procedures were performed under electromyography guidance. A "high potency, low dilution" BoNT-A protocol was applied for oromandibular, lingual, cranial, cervical, and distal limb dystonias; whereas for dystonias of the abdominal, paraspinal, and proximal limb muscles, a "low potency, high dilution" BoNT-A injection protocol was applied. Outcomes measures included: the global dystonia rating scale (DRS) and pain visual analog scale (VAS) reduction at week 4; duration of BoNT-A effects; and, side effect profile. The median DRS score after 4 weeks was 3 ("substantial improvement") for oromandibular and lingual dystonias and 2 ("moderate improvement") for truncal-axial dystonias. Pain reduction was significantly reduced (75%-80% in oromandibular; 30%-80% in truncal-axial dystonias). The median duration of BoNT-A effect was 16 weeks for oromandibular, 12 weeks for lingual, and 11 weeks for truncal-axial dystonias. Compared to a generally safe and well-tolerated BoNT-A injections for truncal-axial dystonias, the oromandibular-lingual dystonias had the following frequency of adverse events: oromandibular--19% in jaw opening and 17% in jaw closing dystonias; lingual--19% in tongue protrusion and 13% in tongue curling dystonias. The most frequent adverse events were mouth dryness and dysphagia. Thus, BoNT-A injection working protocols may be adopted in XDP dystonia that adheres to cost minimization (e.g., lower dose end per selected muscle), while achieving some benefit, and potentially reduce the adverse event profile.     

Neurophysiological effects of botulinum toxin type a

Botulinum toxin type A (BoNT-A) acts peripherally by inhibiting acetylcholine release from the presynaptic neuromuscular terminals, thus weakening muscle contraction, and its clinical benefit depends primarily on the toxin's peripheral action. In addition to acting directly at the neuromuscular junction, the toxin alters sensory inputs to the central nervous system, thus indirectly inducing secondary central changes. Some of the long-term clinical benefits of BoNT-A treatment may also reflect plastic changes in motor output after the reorganization of synaptic density.     

Botulinum toxin A: a new option for treatment of chronic migraine with medication overuse

The application of Botulinum toxin for several pathological conditions has been largely debated in the last decades and its use has been definitively consolidated for disorders related to increased muscle tone and hyperidrosis. Botulinum neurotoxin (BoNT-A) is a potent toxin produced by an anaerobic bacterium, Clostridium botulinum, which presents several pharmacological proprieties, but also different and serious contraindications. As chronic migraine (CM) is commonly reported as a serious and debilitating condition and a big challenge from the therapeutic point of view, in the last decades, after isolated observations, BoNT-A has been applied as preventive treatment for CM patients and, after randomized and rigorous studies, it has been accepted among the most effective pharmacological treatments for these problematic patients. In the present report, a group of patients suffering from CM with medication overuse was treated with BoNT-A to verify its efficacy for CM. The results confirmed the efficacy of BoNT-A when used at the dosage of 155 UI, according with the PREEMPT study protocol. Although these results are preliminary, in a limited group of patients, they led to intense efforts to enforce the use of BoNT-A for CM and to assess its clinical applicability.     

Botulinum toxin type-A treatment in spastic paraparesis: a neurophysiological study

OBJECTIVE: The aim of this study was to verify the action of Botulinum toxin type-A (BoNT-A) by means of neurophysiological techniques, in patients presenting lower limb spasticity and requiring BoNT-A injections in the calf muscles, due to the poor response to medical antispastic treatment. SUBJECTS AND METHOD: Patients presenting paraparesis were enrolled. They underwent clinical evaluation for spasticity according to the Ashworth scale and neurophysiological recordings including: motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) of the leg area; compound motor action potential (cMAP) to tibial nerve stimulation, F-wave, and H-reflex before the treatment and 24 h, 2 weeks and 1 month after the injection of BoNT-A. In all patients, gastrocnemius was treated and in some cases soleus or tibialis posterior muscles were also injected. RESULTS: In all patients, BoNT-A injections induced a clear clinical improvement as showed by the reduced spasticity values of the Ashworth scale. A significant increment of MEP latency and central conduction time (CCT) duration were observed 2 weeks after the treatment only in the injected muscles. CONCLUSIONS: Prolonged MEP latencies and CCT after BoNT-A injections is probably due to a central alteration in responsiveness of spinal motor neurons to descending impulses from the corticospinal tracts. Such changes represent objective parameters heralding clinical efficacy of treatment.     

Determinants of botulinum toxin discontinuation in multiple sclerosis: a retrospective study

The purpose of the present study was to investigate the long-term persistence to treatment with botulinum toxin type A (BoNT-A) for multiple sclerosis (MS)-related spasticity and the determinants of BoNT-A discontinuation in daily clinical setting. We retrospectively collected data of patients who started BoNT-A injections and underwent regular follow-up visits. Determinants of BoNT-A discontinuation were explored in a time-to-event Cox regression analysis which included as independent variables a large set of demographic and clinical characteristics. A total of 185 patients started BoNT-A injections from 2002 to 2014 and were followed up to September 2016. Of them, data on 121 were considered in our analysis. At follow-up, 53 (44%) patients were still on treatment and 68 (56%) patients discontinued BoNT-A after a median time of 1.2 years [interval 6 months to 7.4 years]. The reasons for discontinuation were loss of efficacy (n = 45), logistic problems or barriers to reach the structure (n = 16), and adverse events (n = 7). The absence of caregiver (hazard ratio = 1.69, p = 0.03) and lack of regular rehabilitation (hazard ratio = 1.78, p = 0.02) were two independent predictors for BoNT-A discontinuation. Our study confirms the beneficial effect of combining BoNT-A injections with rehabilitation and highlights the crucial role of caregivers for achieving better long-term outcomes in people with MS suffering from spasticity.     

Long-term efficacy and tolerability of 4-monthly versus yearly botulinum toxin type A treatment for lower-limb spasticity in children with cerebral palsy

In this study, we compared the long-term efficacy and tolerability of two dosage regimens of the potent botulinum toxin type A (BoNT-A; Dysport; Ipsen Ltd, Slough, UK) in children with cerebral palsy (CP) and lower-limb spasticity. Children aged 1 to 8 years with diplegic CP who were able to walk (aided or unaided) were randomized (1:1) to 30 LD₅₀ units/kg total body weight of BoNT-A (injected into gastrocnemius muscles) every 4 months or once yearly for 2 years in this multicentre, assessor-blinded, parallel-group study. In the 4-monthly group ( n =110, 39 males, 71 females), mean age was 3 years 8 months (SD 1y 6mo, range 1–8y). In the yearly group ( n =104, 47 males, 57 females), mean age was 4 years 4 months (SD 1y 6mo, range 2–8y). Both treatment groups had similar baseline Gross Motor Function Measure scores. At month 28 (primary endpoint; intention-to-treat group), median maximum passive ankle dorsiflexion was 12.00° in the 4-monthly and 11.00° in the yearly group. Between-group difference of 1.67° was not statistically significant ( p =0.055). Other efficacy endpoints showed no significant difference between the regimens. The results of the study do not allow a clear conclusion of the preferred injection regimen.     

Long-term incobotulinumtoxinA treatment for chronic sialorrhea: Efficacy and safety over 64 weeks

BackgroundBotulinum neurotoxin (BoNT) is an effective treatment for chronic sialorrhea; however, reliable and robust evidence supporting long-term efficacy and safety is lacking. This study investigated the efficacy and safety of repeated incobotulinumtoxinA injections for chronic sialorrhea over 64 weeks.MethodsAdults with sialorrhea were randomized (2:2:1) to incobotulinumtoxinA 75 U, incobotulinumtoxinA 100 U (n = 74 each), or placebo (n = 36) in the double-blind, placebo-controlled main period (NCT02091739). Eligible subjects entered the extension period and received dose-blinded incobotulinumtoxinA 75 or 100 U in three further 16±2-week injection cycles. Efficacy and safety assessments in subjects who received incobotulinumtoxinA throughout the study included unstimulated salivary flow rate (uSFR), subjects' Global Impression of Change Scale (GICS), Drooling Severity and Frequency Scale (DSFS), modified Radboud Oral Motor Inventory for Parkinson's Disease (mROMP) drooling, speech, and swallowing symptom scores, and incidence of adverse events (AEs).ResultsIn total, 173/184 subjects (94%) completed the main period and entered the extension period; 141 subjects received incobotulinumtoxinA 75 U (n = 69) or 100 U (n = 72) in both periods. Mean uSFR decreased consistently with repeated incobotulinumtoxinA 75 and 100 U treatment and by −0.16 and −0.17, respectively, at the end-of-study visit. Subjects’ GICS, DSFS, and mROMP drooling scores also improved at all assessments. mROMP speech and swallowing scores remained stable. The most common treatment-related AEs during the extension period were dry mouth (4.4% and 11.1%) and dysphagia (1.5% and 4.2%).ConclusionsData support long-term efficacy and safety of repeated incobotulinumtoxinA treatment for sialorrhea, with no additional safety concerns reported over 64 weeks.     

Facial asymmetry in patients with hemifacial spasm before and after botulinum toxin A treatment

Botulinum toxin A (BoNT-A) injection is one of the most widely used methods for hemifacial spasm (HFS) with high efficacy in controlling spasm. However, it is still unknown if esthetic symmetry could be desired as the spasm was controlled by BoNT-A therapy. The purpose of this study is to clarify the facial asymmetric characteristics of HFS patients and if the asymmetry could be amended by BoNT-A injection in the abnormal side. In this prospective analysis, HFS patients were enrolled, who received hemifacial BoNT-A injection and completed follow-up at weeks 2–4. Self-reported improvement and negative influence of facial asymmetry in social life were documented. Facial asymmetry was assessed by the Sunnybrook facial grading system (SFGS) and a new scale created by our clinic—the Symmetry Scale for Hemifacial Spasm (SSHS). Thirty-eight patients were eligible for analysis. Among them, 34 patients (89 %) had marked improvement in spasm after BoNT-A injection. After BoNT-A injection, SFGS showed an improvement of synkinesis (p = 0.01). And SSHS showed an amelioration of resting symmetry in lower face after treatment (p < 0.05). However, SFGS showed a deterioration of voluntary movement in lower face after treatment (p < 0.01). In addition, a deterioration of voluntary movement in upper face and lower face was found in SSHS after treatment (p < 0.01). SSHS composite score showed a deterioration after BoNT-A injection (p = 0.01). In conclusions, BoNT-A was effective in controlling spasm and synkinesis of HFS and improved resting symmetry in lower face, but facial symmetry of voluntary movement deteriorated after hemifacial BoNT-A injection.     

A randomized trial of upper limb botulimun toxin versus placebo injection,combined with physiotherapy,in children with hemiplegia

The main goal of this study was to investigate the efficacy of Botulinum Toxin A (BoNT-A), combined with an individualized intensive physiotherapy/orthoses treatment, in improving upper limb activity and competence in daily activity in children with hemiplegia, and to compare its effectiveness with that of non-pharmacological instruments. It was a Randomized Clinical Trial of 27 children with spastic hemiplegic cerebral palsy, outpatients of two high speciality Centres for child rehabilitation. Each child was assigned by simple randomization to experimental group (BoNT-A) or control group (placebo). Assisting Hand Assessment (AHA) was chosen as primary outcome measure; other measures were selected according to ICF dimensions. Participants were assessed at baseline (T0), at T1, T2, T3 (1–3–6 months after injection, respectively). Every patient was given a specific physiotherapeutic treatment, consisting of individualized goal directed exercises, task oriented activities, daily stretching manoeuvres, functional and/or static orthoses. BoNT-A group showed a significant increase of AHA raw scores at T2, compared to control group (T2–T0: p = .025) and functional goals achievement (GAS) was also slightly better in the same group (p = .033). Other measures indicated some improvement in both groups, without significant intergroup differences. Children with intermediate severity of hand function at House scale for upper limb impairment seem to have a better benefit from BoNT-A protocol. BoNT-A was effective in improving manipulation in the activity domain, in association with individualized goal-directed physiotherapy and orthoses; the combined treatment is recommended. The study brings more evidence for the efficacy of a combined treatment botulinum toxin injection-physiotherapy-orthoses, and it gives some suggestions for candidate selection and individualized treatment.