Botulinum toxin type A in treating early-stage patients with small-angle acute acquired comitant esotropia

AIM:To investigate botulinum toxin A(BTXA)efficacy on small-angle(≤25Δ)acute acquired concomitant esotropia(AACE)in early-stage patients.METHODS:The electronic medical record data of AACE patients during March 2019 and June 2023 were collected in this retrospective and hospital-based cohort study.A total of 72 small-angle AACE patients received BTXA extraocular muscle injection.Patients were grouped by onset-to-treatment time(Group A:≤6mo,Group B:>6mo).Deviation of esotropia,eye alignment and stereopsis were analyzed at the period of pre/post-injection(1wk,1,3,and 6mo).Orthophoria rate at 6mo(horizontal deviation<10Δand binocular single vision)were considered as outcome index.RESULTS:There were no significant baseline differences(P>0.05)between two groups except onset-to-treatment time(2mo vs 11mo,P<0.001).Higher orthophoria rates were in Group A at last follow-up(94.74%vs 73.53%,P=0.013).Post-BTXA deviations of two groups at 1mo showed no difference(P>0.05);while in 3 and 6mo Group A was significantly smaller than group B(all P<0.001).No statistically significant differences were observed among all post-BTXA deviations of near and distance in Group A.In Group B,deviation at 3mo(near:2Δvs 0,P<0.001;distance:4Δvs 0,P<0.001)and 6mo(near:6Δvs 0,P<0.001;distance:6Δvs 0,P<0.001)was significant increased compared to deviation at 1wk after treatment.Group A showed better stereopsis recovery in last follow-up compared to Group B(80″vs 200″,P=0.002).Both groups obtained improved stereopsis after treatment(Group A:80″vs 300″,P<0.001;Group B:200″vs 300″,P=0.037).CONCLUSION:BTXA is effective for AACE with small deviation(≤25Δ)in early stage.Delayed treatment(>6mo)may reduce BTXA efficacy.Early BTXA intervention benefits long-term eye alignment and stereopsis recovery.

Botulinum toxin type A-targeted SPP1 contributes to neuropathic pain by the activation of microglia pyroptosis

BACKGROUND Neuropathic pain(NP)is the primary symptom of various neurological condi-tions.Patients with NP often experience mood disorders,particularly depression and anxiety,that can severely affect their normal lives.Microglial cells are as-sociated with NP.Excessive inflammatory responses,especially the secretion of large amounts of pro-inflammatory cytokines,ultimately lead to neuroinflam-mation.Microglial pyroptosis is a newly discovered form of inflammatory cell death associated with immune responses and inflammation-related diseases of the central nervous system.METHODS Two models,an in vitro lipopolysaccharide(LPS)-stimulated microglial cell model and a selective nerve injury model using BTX-A and SPP1 knockdown treatments,were used.Key proteins in the pyroptosis signaling pathway,NLRP3-GSDMD,were assessed using western blotting,real-time quantitative polymerase chain reaction,and immunofluorescence.Inflammatory factors[interleukin(IL)-6,IL-1β,and tumor necrosis factor(TNF)-α]were assessed using enzyme-linked immuno-sorbent assay.We also evaluated microglial cell proliferation and apoptosis.Furthermore,we measured pain sensation by assessing the delayed hind paw withdrawal latency using thermal stimulation.RESULTS The expression levels of ACS and GSDMD-N and the mRNA expression of TNF-α,IL-6,and IL-1βwere enhanced in LPS-treated microglia.Furthermore,SPP1 expression was also induced in LPS-treated microglia.Notably,BTX-A inhibited SPP1 mRNA and protein expression in the LPS-treated microglia.Additionally,depletion of SPP1 or BTX-A inhibited cell viability and induced apoptosis in LPS-treated microglia,whereas co-treatment with BTX-A enhanced the effect of SPP1 short hairpin(sh)RNA in LPS-treated microglia.Finally,SPP1 depletion or BTX-A treatment reduced the levels of GSDMD-N,NLPRP3,and ASC and suppressed the production of inflammatory factors.CONCLUSION Notably,BTX-A therapy and SPP1 shRNA enhance microglial proliferation and apoptosis and inhibit microglial death.It improves pain perception and inhibits microglial activation in rats with selective nerve pain.

Prospective observational study to assess the validity of the functional disability score in patients with blepharospasm,hemifacial spasm and synkinesis treated with botulinum toxin injection

Background:Benign essential blepharospasm(BEB),aberrant facial nerve degeneration and hemifacial spasm(HFS)are all examples dystonia which,though not life-threatening,can have a significant impact on patient quality of life.The need for reliable self-rating surveys to monitor functional disability is fundamental.The Blepharospasm Disability Index(BSDI)is already a widely utilised and validated selfrating score for blepharospasm whilst the functional disability score(FDS)requires further validation.The principle aim of this study is to repeat validation of the FDS against the BSDI,which has been validated by several groups since its original description but only in patients with BEB.Methods:A randomised blinded prospective cohort study was conducted at a single unit on 38 patients with BEB,aberrant facial nerve degeneration and HFS.Patients were blinded to complete the FDS followed by the BSDI or the BSDI followed by the FDS with a 30-minute interval.Results:Both the FDS and BSDI were found to be reliable with high internal consistency and test-retest reliability.Both scales were also found to be moderately correlated with the Jankovic disease severity score.Conclusions:This study is the first to use the FDS as a rating scale in patients with HFS and aberrant facial nerve degeneration.It is also the first study to formally validate the FDS as an acceptable rating scale for patients with dystonia and in particular it provides validation for its use in patients with HFS and aberrant facial nerve degeneration.

Systematic evaluation of the efficacy and safety of botulinum toxin type A in the treatment of spastic cerebral palsy

Background:Botulinum toxin type A(BTX-A)is a neuromuscular blocking agent.BTX-A inhibits acetylcholine release,causes neuromuscular transmission impairment,and decreases muscle spasms.Objective:To explore the efficacy and safety of BTX-A injection in the treatment of spastic cerebral palsy through systematic evaluation and to provide a reference for the clinical use of BTX-A.Methods:We used“Cerebral palsy”and“BTX-A”as the subject terms and used a combination of subject terms and free words for the search.We searched 7 databases,including CNKI,Wanfang,VIP,Sinomed,PubMed,Embase,and Web of science.Based on the inclusion and exclusion criteria,we screened the articles by reading their titles,abstracts,and full texts and finally included relevant literature for systematic evaluation.Result:A total of 93 papers were systematically evaluated,revealing that BTX-A injection treatment can effectively reduce muscle tone,increase joint mobility,improve gait and motor posture,and enhance gross motor movements in patients with spastic cerebral palsy.The benefits of BTX-A treatment can be sustained for 3–6 months,with motor ability improvement lasting up to 1 year.Combining BTX-A treatment with rehabilitation or external fixation therapy can enhance its efficacy.However,the effectiveness of BTX-A treatment is influenced by several factors,such as the dosage,number of injections,and patient age.Adverse reactions to BTX-A treatment are typically mild and can be relieved within 1–2 weeks.Conclusion:BTX-A injection is relatively safe but reversible.

Botulinum toxin injection improved voluntary motor control in selected patients with post-stroke spasticity

The effect of botulinum toxin type A injection on voluntary grip control was examined in a 53-year-old female, who sustained a hemorrhagic right middle cerebral artery stroke 3 years previously, which resulted in finger flexor spasticity and residual weak finger/wrist extension. The patient received 50 units of botulinum toxin type A injection each to the motor points （2 sites/muscle） of the left flexor digitorum superficialis and flexor digitorum profundus, respectively. Botulinum toxin injection led to weakness and tone reduction in the spastic finger flexors, but improved grip release time in grip initiation/release reaction time tasks. Improved release time was accompanied by shortened extensor electromyography activity, and improved release time likely correlated with blocked co-contraction of finger flexors during voluntary finger extension. This case report demonstrated that botulinum toxin injection improved voluntary motor control of the hand in a chronic stroke patient with residual finger extension.

Therapeutic efficacy and safety of various botulinum toxin A doses and concentrations in spastic foot after stroke: a randomized controlled trial

No recommended guidelines currently exist for the therapeutic concentration or dose of botulinum toxin type A （BTXA） injected into the muscle to treat limb spasticity. Therefore, in this randomized controlled trial, we explored the safety and efficacy of two concentrations and two doses of BTXA in the treatment of spastic toot after stroke to optimize this treatment in these patients. Eligible patients （n = 104） were randomized into four groups. The triceps surae and tibialis posterior on the affected side were injected with BTXA at one of two doses （200 U or 400 U） and two concentrations （50 U/mL or 100 U/mL）. 2he following assessments were conducted before as well as 4 days and 1, 2, 4, and 12 weeks after treatment： spasticity, assessed using the modified Ashworth scale; basic functional mobility, assessed using a timed up and go test; pace, assessed using a 10-meter timed walking test; and the ability to walk, assessed using Holden＇s graded scale and a visual analog scale. The reported results are based on the 89 patients that completed the study. We found significant differences for the two doses and concentrations of BTXA to improve the ability of patients to walk independently, with the high-dose/low-concentration combination providing the best effect. Onset and duration of the ameliorating effects of BTXA were 4-7 days and 12 weeks, respectively. Thus, BTXA effectively treated foot spasms after stroke at an optimal dose of 400 U and concentration of 50 U/mL.

Botulinum toxin A inhibits salivary secretion of rabbit submandibular gland

Botulinum toxin A （BTXA） has been used in several clinical trials to treat excessive glandular secretion; however, the precise mechanism of its action on the secretory function of salivary gland has not been fully elucidated. In this study, we aimed to investigate the effect of BTXA on secretion of submandibular gland in rabbits and to identify its mechanism of action on the secretory function of salivary gland. At 12 weeks after injection with 5 units of BTXA, we found a significant decrease in the saliva flow from submandibular glands, while the salivary amylase concentration increased. Morphological analysis revealed reduction in the size of acinar cells with intracellular accumulation of secretory granules that coalesced to form a large ovoid structure. Expression of M3-muscarinic acetylcholine receptor （M3 receptor） and aquaporin-5 （AQP5） mRNA decreased after BTXA treatment, and distribution of AQP5 in the apical membrane was reduced at 1, 2 and 4 weeks after BTXA injection. Furthermore, BTXA injection was found to induce apoptosis of acini. These results indicate that BTXA decreases the fluid secretion of submandibular glands and increases the concentration of amylase in saliva. Decreased expression of M3 receptor and AQP5, inhibition of AQP5 translocation, and cell apoptosis might involve in BTXA-reduced fluid secretion of submandibular lands.

Botulinum toxin injections after surgery for Hirschsprung disease:Systematic review and meta-analysis

BACKGROUND A large proportion of patients with Hirschsprung disease experience persistent obstructive symptoms after corrective surgery.Persistent obstructive symptoms may result in faecal stasis that can develop into Hirschsprung-associated enterocolitis,a potential life-threatening condition.Important treatment to improve faecal passage is internal anal sphincter relaxation using botulinum toxin injections.AIM To give an overview of all empirical evidence on the effectiveness of botulinum toxin injections in patients with Hirschsprung disease.METHODS A systematic review and meta-analysis was done by searching PubMed,EMBASE and the Cochrane Library,using entry terms related to:(1)Hirschsprung disease;and(2)Botulinum toxin injections.14 studies representing 278 patients met eligibility criteria.Data that were extracted were proportion of patients with improvement of obstructive symptoms or less enterocolitis after injection,proportion of patients with adverse effects and data on type botulinum toxin,mean dose,average age at first injection and patients with associated syndromes.Random-effects meta-analysis was used to aggregate effects and random-effects meta-regression was used to test for possible confounding factors.RESULTS Botulinum toxin injections are effective in treating obstructive symptoms in on average 66%of patients[event rate(ER)=0.66,P=0.004,I2=49.5,n=278 patients].Type of botulinum toxin,average dose,average age at first injections and proportion of patients with associated syndromes were not predictive for this effect.Mean 7 duration of improvement after one botulinum toxin injections was 6.4 mo and patients needed on average 2.6 procedures.There was a significant higher response rate within one month after botulinum toxin injections compared to more than one month after Botulinum toxin injections(ER=0.79,vs ER=0.46,Q=19.37,P<0.001).Botulinum toxin injections were not effective in treating enterocolitis(ER 0.58,P=0.65,I2=71.0,n=52 patients).There were adverse effects in on average 17%of patients(ER=0.17,P<0.001,I2=52.1,n=187 patients),varying from temporary incontinence to mild anal pain.CONCLUSION Findings from this systematic review and meta-analysis indicate that botulinum toxin injections are effective in treating obstructive symptoms and that adverse effects were present,but mild and temporary.

Efficacy and safety of botulinum toxin in treatment of anismus: A systematic review

AIM: To evaluate the efficacy and safety of botulinum toxin type A(BTX-A) in the management of patients with anismus. METHODS: An organized search of published literature was conducted using electronic databases including: Pub Med/MEDLINE, and Cochrane Central Register of Control ed Trials, also an internet-based search using "Google Scholar" service was conducted. Both comparative and observational studies were included. We excluded irrelevant articles, editorials, case reports, reviews, and meta-analyses. The studies that followed the patients less than 6 mo were excluded. Variables collected were demographic data of the patients, technique of BTX-A injection and number of sessions, short-term and longterm clinical improvement, post-injection changes in electromyography(EMG), defecography, manometry, and balloon expulsion test, and complications recorded after BTX-A injection.RESULTS: Seven studies comprising 189 patients were included in the review. The median age of the patients was 41.2 years and female-to-male ratio was 1.3:1. The median dose of BTX-A injected per procedure was 100 IU(range, 20-100 IU). Lateral injection was done in five trails and combined lateral and posterior injections in two trials. Three studies used endorectal ultrasonographyguided technique, one study used EMG-guided technique,whereas the remaining three studies used manual palpation with the index finger. The median percentage of patients who reported initial improvement of symptoms was 77.4%(range 37.5%-86.7%), this percentage declined to a median of 46%(range 25%-100%) at 4 mo after injection of BTX-A. Rates of improvement evaluated by balloon expulsion test, EMG, and defecography ranged between(37.5%-80%),(54%-86.7%), and(25%-86.6%), respectively. Fourteen(7.4%) patients developed complications after injection of BTX-A. Complication rates across the studies ranged from 0% to 22.6%. CONCLUSION: Initial satisfactory improvement of symptoms after BTX-A injection remarkably deteriorated after 3 mo of the procedure. However, repeated injection may provide better sustained results with no additional morbidities. Further analysis of more patients is necessary to conclude the safety of BTX-A for the treatment of anismus.

Clinical efflcacy of botulinum toxin type A on acute acquired comitant esotropia

AIM: To investigate the effects of micro-injection of botulinum toxin A(BTXA) on acute acquired comitant esotropia(AACE). METHODS: A total of 33 AACE patients who underwent BTXA micro-injection at Renmin Hospital of Wuhan University from September 1^(st), 2019 to July 1^(st), 2021 were retrospective analyzed. Esotropia, eye alignment, stereopsis, and complications were examined at baseline(except complications), 1wk, 1, 3, and 6mo after injection. RESULTS: The average angle of deviation before injection was(+20.24±6.80)^(Δ) at near and(+24.76±6.43)^(Δ) at distance, while(+5.15±5.85)^(Δ) at near and(+7.30±6.17)^(Δ) at distance 6mo after treatment(P<0.05). Six months after injection, the stereopsis of patients had improved. The number of patients having no stereopsis(>800 seconds of arc) decreased from 11 to 3. The number of patients having peripheral stereopsis(300-800 seconds of arc), macular stereopsis(70-200 seconds of arc) and central concave stereopsis(≤60 seconds of arc) increased from 10 to 11, 10 to 12, and 2 to 7, respectively. At the follow-ups at 1wk, 1, 3, and 6mo after injection, success rates were 96.97%, 96.97%, 93.94% and 87.88%, respectively. One week after injection, two patients(6.07%) showed subconjunctival hemorrhage;three patients(9.09%) showed limited eye movement and one patient(3.03%) showed mild vertical strabismus. All the symptoms disappeared by the final follow-up.CONCLUSION: Micro-injection of BTXA can reduce diplopia and improve binocular vision function of AACE patients. Furthermore, the operation is relatively safe with few complications, making it an ideal treatment modality for AACE.

CLINICAL APPLICATION OF BOTULINUM TOXIN TYPE B IN MOVEMENT DISORDERS AND AUTONOMIC SYMPTOMS

Objective To evaluate efficacy and safety of botulinum toxin type B (BTX-B) in treatment of movement disorders including blepharospasm, oromandibular dystonia, hemifacial spasm, tremor, tics, and hypersecretory disorders such as sia-lorrhea and hyperhidrosis. Methods A retrospective study of BTX-B injections in treatment of 58 patients with various neurological disorders was performed. The mean follow-up time was 0.9 ± 0.8 years. Results of the first and last treatment of patients with at least 3 injection sessions were compared. Results The response of 58 patients to a total of 157 BTX-B treatment sessions was analyzed. Of the 157 treatment sessions, 120 sessions (76.4%) resulted in moderate or marked improvement while 17 sessions (10.8%) had no response. The clinical benefits after BTX-B treatment lasted an average of 14 weeks. Of the 41 patients with at least 3 injection ses-sions (mean 10 ± 8.6), most patients needed increased dosage upon the last session compared to the first session. Nineteen patients (32.8%) with 27 sessions (17.2%) reported adverse effects with BTX-B treatment. Conclusions Though most patients require increased dosage to maintain effective response after repeated injections, BTX-B is an effective and safe treatment drug for a variety of movement disorders, as well as drooling and hyperhidrosis.

Botulinum toxin associated with fissurectomy and anoplasty for hypertonic chronic anal fissure: A case-control study

BACKGROUND Lateral internal sphincterotomy is still the approach of choice for the treatment of chronic anal fissure(CAF)with internal anal sphincter(IAS)hypertonia,but it is burdened by high-risk postoperative faecal incontinence(FI).Sphincter saving procedures have recently been reconsidered as treatments to overcome this risk.The most employed procedure is fissurectomy with anoplasty,eventually associated with pharmacological sphincterotomy.AIM To evaluate whether fissurectomy and anoplasty with botulinum toxin injection improves the results of fissurectomy and anoplasty alone.METHODS We conducted a case-control study involving 30 male patients affected by CAF with hypertonic IAS who underwent fissurectomy and anoplasty with V-Y cutaneous flap advancement.The patients were divided into two groups:Those in group I underwent surgery alone,and those in group II underwent surgery and a botulinum toxin injection directly into the IAS.They were followed up for at least 2 years.The goals were to achieve complete healing of the patient and to assess the FI and recurrence rate along with manometry parameters.RESULTS The intensity and duration of post-defecatory pain decreased significantly in both groups of patients starting with the first defecation,and this reduction was higher in group II.Forty days after surgery,we achieved complete wound healing in all the patients in group II but only in 80%of the patients in group I(P<0.032).We recorded 2 cases of recurrence,one in each group,and both healed with conservative therapy.We recorded one temporary and low-grade postoperative case of“de novo”FI.Manometry parameters reverted to the normal range earlier for group II patients.CONCLUSION The injection of botulinum toxin A in association with fissurectomy and anoplasty with a V-Y advancement flap improves the results of surgery alone in patients affected by CAF with IAS hypertonia.

Use of Clostridium botulinum toxin in gastrointestinal motility disorders in children

More than a century has elapsed since the identification of Clostridia neurotoxins as the cause of paralytic diseases. Clostridium botulinum is a heterogeneous group of Gram-positive, rod-shaped, spore-forming, obligate anaerobic bacteria that produce a potent neurotoxin. Eight different Clostridium botulinum neurotoxins have been described(A-H) and 5 of those cause disease in humans. These toxins cause paralysis by blocking the presynaptic release of acetylcholine at the neuromuscular junction. Advantage can be taken of this blockade to alleviate muscle spams due to excessive neural activity of central origin or to weaken a muscle for treatment purposes. In therapeutic applications, minute quantities of botulinum neurotoxin type A are injected directly into selected muscles. The Food and Drug Administration first approved botulinum toxin(BT) type A in 1989 for the treatment of strabismus and blepharospasm associated with dystonia in patients 12 years of age or older. Ever since, therapeutic applications of BT have expanded to other systems, including the gastrointestinal tract. Although only a single fatality has been reported to our knowledge with use of BT for gastroenterological conditions, there are significant complications ranging from minor pain, rash and allergic reactions to pneumothorax, bowel perforation and significant paralysis of tissues surrounding the injection(including vocal cord paralysis and dysphagia). This editorial describes the clinical experience and evidence for the use BT in gastrointestinal motility disorders in children.

THE PROPERTIES AND LONGITUDINAL EXPERIENCE OF CHINESE TYPE A BOTULINUM TOXIN FOR THE TREATMENT OF FOCAL DYSTONIA AND HEMIFACIAL SPASM

Objective.To introduce the properties of Chinese type A botulinum toxin(CBTXA,made by Lanzhou Institute of Biological Products),and its long?term effect for focal dystonia and hemifacial spasm.Method.The purity and recovery of crude and crystalline toxin were tested.Long?term data from305patients with hemifacial spasm(HFS),blepharospasm(BS)and cervical dystonia(CD)were evalu-ated and subgroups of patients received CBTXA injections between1994and2000in at least six sepa-rate treatment sessions,with follow up for2～8years.The therapeutic results of the last session CBTXA injections were analyzed in comparison with the first session.Result.CBTXA purity was high[(2.55～2.60)×10 7 LD50/mgPr ,A260/A280≤0.55,high molecular substance accounted for99.2%of total proteins].Long term treatment with CBTXA in patients with focal dystonia and HFS was not associated with any decline in benefit,and efficacy may improve slightly with repeat treatments.CBTXA is an excellent long-term treatment of HFS,BS and CD.Conclusion.We conclude that Chinese type A botulinum toxin is of botulinum toxin therapy quality standard according to results obtained from the basic study and long?term clinical applications.The re?injection of CBTXA significantly improves the quality of life of most patients and is a safe,effective and comparatively economical treatment for patients with focal dystonia and HFS.

Therapeutic Outcome of Botulinum Toxin Type A for Patients with Low Bladder Compliance Secondary to Spinal Cord Injury

Objective: To evaluate the efficacy and safety of botulinum toxin type A (BTX-A) in treating patients with low bladder compliance (BC) secondary to spinal cord injury (SCI). Methods: From 2011 to 2016, we retrospected patients who received BTX-A injections for LBC secondary to SCI. The primary outcomes were urodynamic parameters including maximum detrusor pressure (Pdetmax), bladder compliance (BC). Related adverse events were recorded. Results: 72 SCI patients were selected (62 males, 10 females, age range 18 - 52 years;mean age 28.5 years). 12 weeks after BTX-A injection, Pdetmax decreased from 51.02 cmH2O to 28.31 cmH2O. BC increased from 3.64 ml/cmH2O to 10.08 ml/cmH2O. 12 patients had mild transient haematuria for 1 - 2 days. Conclusion: Intradetrusor BTX-A injection was effective and safe for patients with low BC secondary to SCI.

Botulinum toxin for chronic anal fissure after biliopancreatic diversion for morbid obesity

AIM: To study the effect of botulinum toxin in patients with chronic anal fissure after biliopancreatic diversion (BPD) for severe obesity. METHODS: Fifty-nine symptomatic adults with chronic anal fissure developed after BPD were enrolled in an open label study. The outcome was evaluated clinically and by comparing the pressure of the anal sphincters before and after treatment. All data were analyzed in univariate and multivariate analysis. RESULTS: Two months after treatment, 65.4% of the patients had a healing scar. Only one patient had mild incontinence to flatus that lasted 3 wk after treatment, but this disappeared spontaneously. In the multivariate analysis of the data, two registered months after the treatment, sex (P = 0.01), baseline resting anal pressure (P = 0.02) and resting anal pressure 2 mo after treatment (P < 0.0001) were significantly related to healing rate.CONCLUSION: Botulinum toxin, despite worse results than in non-obese individuals, appears the best alternative to surgery for this group of patients with a high risk of incontinence.

Treatment with botulinum toxin: An update

Botulinum neurotoxin(Bo NT) is a potent toxin produced by the anaerobic bacterium clostridium botulinum. It causes flaccid, long-lasting, local and reversible paralysis. In addition, Bo NT inhibits the secretion of the exocrine glands and could have properties in the control of pain. Thus, Bo NT is useful in the treatment of many neuromuscular conditions where an increase of muscle tone is associated with the pathogenic mechanism. Furthermore, Bo NT is recommended in the treatment of some hypersecretion disorders of the exocrine gland and could play a role in the treatment of migraine and other chronic pain conditions. In the Bo NT therapy adverse effects are usually mild and reversible. However, repeated injections of Bo NT can lead to the development of neutralizing antibodies that can subsequently inhibit the biological activity of the toxin. In this sense, many factors can influence the immunogenicity of the Bo NT, such as product-related factors, the dose of Bo NT used, the frequency of injection and the previous exposure to the toxin. In this review, we are going to discuss the current clinical applications of Bo NT with a special focus on evidence, doses, injection technique and adverse effects for those applications more frequently used in neurology, namely spasticity, blepharospasm, hemifacial spasm, cervical dystonia and other focal dystonias, as well as chronic migraine, tremor, sialorrhea, facial palsy, neurogenic bladder and many other neurological condition.

Botulinum toxin and benign prostatic hyperplasia

Benign prostatic hyperplasia(BPH)is a clinical condition where lower urinary tract symptoms are caused by both a physically obstructing prostate as well as tight smooth muscles around the bladder outlet.Treatment of this condition with botulinum toxin has been used since 2003,but this interest has somewhat died down after two large randomized controlled trials(RCTs)showing equivalence of results between their treatment and placebo arms.However,with review of animal studies and unexplained exaggerated effect of the placebo arms of the two RCTs,together with recent data of sustained benefits after 18 months of treatment,the place of botulinum toxin in the BPH field is probably still present.

Efficacy of Carbamazepine Combined with Botulinum Toxin A in the Treatment of Blepharospasm and Hemifacial Spasm

Purpose:To observe the efficacy of the combined treatment of carbamazepine and botulinum toxin A for blepharospasm and hemifacial spasm. Methods:Fifty-eight patients with either blepharospasm or hemifacial spasm were randomly divided into treatment and control groups. In the treatment group, 30 patients were administered with local intramuscular injections of botulinum toxin A and oral carbamazepine 100 mg/time,3 times/day for 60 days. Twenty-eight subjects in the control group under-went local intramuscular injections of botulinum toxin A only. Results:After combined treatment, the complete remission rate was 90%, which was significantly higher than that of the of the control group (67.9% , P<0.05,χ2 =4.733). However, no statistical significance was noted regarding the duration of therapeutic effects between the treatment group (range 14～40 weeks; 19.2 weeks on average) and control group (range 12～36 weeks; 18 weeks on average). Conclusion:The combined therapy of carbamazepine and topical injections of botulinum toxin A had increased efficacy in the treatment of blepharospasm or hemifacial spasm, but had no significant effect in terms of the duration of the therapeutic effect.

Distribution of the Toxin following Medial Rectus Muscular Injection of Botulinum Toxin Gel in Rabbits

Purpose: To determine the distribution of the toxin among individual muscles after intramuscular injection of botulinum toxin gel.Methods: One eye of 7 New Zealand white rabbits was randomized into group A, and the contralateral eye was into group B. Eyes in group A received medial rectus intramuscular injection of 2.5 IU of 125I-BTX-A gel in 0.1 ml, and those in group B received equivalent amount of 125I-BTX-A solution by medial rectus intramuscular injection. Four rectus muscles and the levator palpebrae superioris were harvested and the radioactivity of muscles was measured 16 hours after the injection.Results: In group A, the radioactivity of per gram medial rectus was significantly higher than that of other muscles (P ＜ 0.01), and there was no statistically significant difference in the radioactivity of per gram muscles among other muscles (P ＞ 0.05). In group B, the radioactivity of per gram medial rectus and levator palpebrae superioris was significantly higher than that of other muscles respectively(P ＜ 0.05), and the difference in the radioactivity of per gram muscles between medial rectus and levator palpebrae superioris was not statistically significant (P ＞ 0.05). The radioactivity of per gram medial rectus in group A was higher than that in group B (t=3.731 ,P=0.01), and there was no significant difference in the radioactivity of per gram muscles among other homonymous muscles (P ＞ 0.05).Conclusion: The toxin dispersed principally in the injected muscle and the local concentration of the toxin was much high following intramuscular injection of botulinum toxin gel.