Botulinum toxin A for the treatment of achalasia

Pneumatic balloon dilatation of the esophagus is one of the current recommended treatment for achalasia. This procedure is associated with risks such as esophageal rupture. Surgery and percutaneous gastrostomy tube placement has been performed in severely affected individuals. The Botulinum Toxin A (BoTxA) is widely used to treat neuromuscular conditions in which spasticity is of concern. We present four cases in which BoTxA was used as an alternative of treatment and in which less invasive modalities were unsuccessful. The patients received a total of 80 units of BoTxA, applied to the submucosa in doses of 20 units in each predetermined quadrants to the lower esophageal sphincter. All patients demonstrated improvement of their symptoms without side effects in this study.     

Botulinum toxin A in the treatment of adherence syndrome

The effect of botulinum toxin A is investigated in the treatment of adherence syndrome related to strabismus surgery. An 18-year-old boy with decompensated right congenital fourth nerve palsy underwent ipsilateral superior rectus muscle recession and inferior oblique muscle disinsertion. During the early postoperative period, a right hypotropia with limitation of elevation developed and the result of the forced duction test was positive for passive elevation of the right eye. Botulinum toxin A was injected into the right inferior rectus muscle on the 15th postoperative day and orthophoria was achieved 1 week later. A repeat injection of botulinum toxin A was performed 6 months later. On follow-up 2 1/2 years later, his eyes remained orthophoric with limitation of elevation in the right eye and the patient was satisfied with the result. This case demonstrated that adherence syndrome can be treated successfully by botulinum toxin A injection if it is administered during the acute phase, before the development of fibrous scar tissue.     

Botulinum toxin type A purified neurotoxin complex for the treatment of blepharospasm: a dose-response study measuring eyelid force

The clinical efficacy of botulinum toxin type A was studied in patients with blepharospasm. Clinical symptoms were evaluated using the Jankovic rating scale. To measure dose response, we used a recently developed device to measure eyelid muscle force. The results showed significant improvement (P = 0.0000) in the Jankovic rating scale scores in all dose groups. The number of patients with marked improvement (6-point decrease or more in the total Jankovic rating scale score) increased with higher dose injections. After injections of 0.50, 1.25, or 2.50 U/site, 6 sites/eye, the eyelid muscle force decreased by 33.2 +/- 28.1%, 41.7 +/- 25.1%, or 69.6 +/- 5.0%, respectively. The decrease of eyelid muscle force showed a significant dose response (P = 0.0254). The mean duration of effect was 12.9 weeks in patients after dose injections of 1.25 U/site, which was significantly longer (P = 0.0205) than the 9.6 weeks in patients after dose injections of 0.50 U/site. No severe adverse effects were observed. We concluded that injections of botulinum toxin type A at an initial dose of 1.25 U/site are a safe and effective treatment for blepharospasm.     

Botulinum toxin injection effective for post-peripheral facial nerve palsy synkinesis]

Facial synkinesis is an involuntary activation of muscles innervated by the zygomatic or mandibular branch of the facial nerve in conjunction with voluntary activation of the other branch. It appears frequently after recovery from peripheral facial nerve paralysis. We report 10 patients with facial synkinesis following Bell's palsy with a mean duration of synkinesis of 7 +/- 4 years before treatment with periorbital injections of Botulinum toxin type A. 9 had marked subjective and objective improvement starting a few days after injection and lasting 4-9 months. The results suggest a useful treatment option for post-Bell's palsy facial synkinesis with Botulinum toxin type A.     

Botulinum toxin for the treatment of hyperfunctional lines of the face

OBJECTIVE: To determine the effectiveness of botulinum toxin injections for the management of hyperfunctional facial lines in patients with dystonia. DESIGN: Twenty-six patients were included in the study: 24 patients had dystonic movement of the face as either a primary or secondary component, and two patients were treated for purely hyperfunctional lines. Botulinum toxin type A was injected via a monopolar hollow-bore Teflon-coated electromyography needle into the facial muscles associated with the hyperfunctional lines. Doses were divided into 1.25- to 10-U aliquots. Qualitative assessments by the patient and physician were made before injection and 2 to 3 weeks after injection. PATIENTS: Twenty-six patients (two male and 24 female) with hyperfunctional lines were included. The ages were from 32 to 84 years with an average age of 59 years. Twenty had dystonia, four had hemifacial spasm, and two had pure hyperfunction without neuromuscular disease. RESULTS: All of the patients had an effect of toxin within the first 24 to 72 hours. All of the patients experienced benefit from the toxin injections with partial or total resolution of painful contractions or unsightly hyperfunctional lines and spasms. The effects of the injection lasted 3 to 6 months. No systemic side effects were noted. Adverse effects included mild, temporary eyelid or lip weakness. CONCLUSION: Based on this initial pilot study, botulinum toxin may be an important new option for the treatment of patients with hyperfunctional facial lines.     

Botulinum A toxin for glabellar wrinkles. Dose and response

BACKGROUND: Botulinum A exotoxin injection is a well-established method for treatment of glabellar frown lines, crow's feet, and horizontal furrows of the forehead. However, there is no consensus as to the optimal dosage per injection site or the concentration of injectate to be used. OBJECTIVE: The purpose of this study was to determine the minimal effective dose per injection site to be used as well as the effect of concentration in response to treatment. RESULTS: A total of 46 subjects were divided into ten groups and injected with escalating doses and concentrations of botulinum toxin. The response and longevity of treatment were then followed on a monthly basis. A dose between 2.5-4 U per injection site (12.5-20 U total) was determined to be an effective starting dose, with a duration of 2-5 months (median 14 weeks). CONCLUSIONS: There was no statistically significant difference in safety or efficacy for concentrations ranging from 50 to 200 U/ml of botulinum toxin.     

Botulinum toxin management of childhood intermittent exotropia

OBJECTIVE: Intermittent exotropia is a common form of childhood strabismus that has a late onset and presents a difficult and frustrating management dilemma. Surgical treatments have a high recurrence rate, and multiple surgeries often are required to achieve a desirable motor outcome. This study presents long-term observations on the use of botulinum toxin for the treatment of intermittent exotropia in children. DESIGN: This study is a nonrandomized, case-controlled study of consecutive pediatric patients who had intermittent exotropia. PARTICIPANTS: Thirty-two neurologically normal children ranging from 3 to 144 months in age were diagnosed with intermittent exotropia with a minimum distance deviation of 15 prism diopters (PD). INTERVENTION: Simultaneous bilateral injections of 2.5 units botulinum toxin type A were made into the lateral rectus muscles with the patient receiving nitrous oxide-ethrane inhalation anesthesia. Patients were observed for 12 to 44 months after the initial injection. MAIN OUTCOME MEASURES: A satisfactory outcome was considered to be stable binocular alignment of the eyes to an orthophoric range of +/-10 PD. RESULTS: Bilateral lateral rectus muscle injections of botulinum toxin were effective in reducing the mean preinjection deviation of -29 PD to an average exotropic angle of -6 PD. Stable orthophoria (+/-10 PD) was achieved in 22 patients (69%). Overall, male patients required significantly fewer injections than did female patients. All patients between 24 and 56 months of age, irrespective of gender, required only a single bilateral injection to achieve a favorable motor outcome. CONCLUSIONS: Botulinum toxin is at least as effective as surgical outcomes reported previously for the treatment of intermittent exotropia in children. This treatment method is particularly effective in children between 2 and 4.5 years of age irrespective of the initial strabismic angle and is not associated with any secondary abnormalities.     

Botulinum toxin as an adjunct for the treatment of acute anteromedial arytenoid dislocation

Serum creatinine, a surrogate for both renal function and homocysteine generation, is an important determinant of fasting plasma total homocysteine levels in stable renal transplant recipients. In this study, it is hypothesized that among stable renal transplant recipients with normal creatinine levels (i.e., < or = 1.5 mg/dl), serum cystatin C, a more sensitive indicator of GFR, would better predict fasting total homocysteine levels compared with serum creatinine. Fasting plasma total homocysteine, folate, vitamin B12, and pyridoxal 5'-phosphate levels, along with serum cystatin C, creatinine, and albumin levels, were determined in 28 consecutive renal transplant recipients (mean age 47 +/- 14 yr; 60.7% men) with stable allograft function, whose serum creatinine was < or = 1.5 mg/dl. General linear modeling with analysis of covariance revealed that serum cystatin C was independently predictive (partial R = 0.494; P = 0.023) of fasting total homocysteine levels after adjustment for age, gender, vitamin status, albumin, and creatinine levels. In contrast, creatinine levels were not predictive of fasting total homocysteine levels in this model (P = 0.110) or an identical model that excluded cystatin C (P = 0.131). Serum cystatin C levels may reflect subtle decreases in renal function that independently predict fasting total homocysteine levels among stable renal transplant recipients with a normal serum creatinine.     

The resection of gastrocnemius muscles in aesthetically disturbing calf hypertrophy

In some patients, oversized calves lead to mental distress and avoidance of certain social activities. They hide their legs in pants and seek medical advice. If the thickness of the subcutaneous fat is normal and cannot be diminished by liposuction, the oversized calves are caused by pure muscle hypertrophy. Using the gastrocnemius for muscle flaps in covering knee defects does not impair the function of the patient's leg; therefore, resection of the total gastrocnemius muscle for aesthetic calf reduction was performed in 15 consecutive patients without any lasting impairment with stability or sports activities. The patient was placed in a prone position, and the muscles were bluntly freed and pulled through two incisions of 5-cm length in the hollow of the knee and above the Achilles tendon. The resected muscles weighed between 410 and 810 g each. In two patients, the sural nerve was stretched or cut during the operation. The consequent numbness of the lateral ankle and sole persisted for 9 and 13 months, respectively. All 15 patients were satisfied with the results; none complained of lack of stability or insecurity in walking; and all became active in sports or changed their dress habits.     

Botulinum toxin in the therapy of gustatory sweating

A case of mucin-producing adenocarcinoma arising from a mature cystic teratoma of the right ovary is reported in a 67-year-old multiparous Japanese woman. The patient underwent total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and adjuvant chemotherapy containing cisplatin, Adriamycin, and cyclophosphamide with the diagnosis of ovarian cancer, probable stage Ic. Treatment was successful even though the tumor extended through the cyst wall.     

The treatment of hemifacial spasm using botulinum toxin]

Hemifacial spasm is a disagreeable disturbance with involuntary unilateral twitching of the facial muscles. Its most common form is supposedly due to an irritation of the facial nerve at its proximal intracranial segment by vascular structures. Various forms of treatment including surgical procedures are employed, very often without satisfactory results but frequently involving the risk for severe complications. For a few years a new method has been using injection of botulinum toxin into the affected muscles, which in the majority of patients relieves the abnormal movements for about half a year; therefore, this very effective and secure procedure is recommended as first-line treatment of hemifacial spasm.     

Botulinum toxin A, adjunctive therapy for refractory headaches associated with pericranial muscle tension

A set of neurofibromatosis type 1 (NF1) patients was screened for large NF1 gene deletions by comparing patient and parent genotypes at 10 intragenic polymorphic loci. Of 67 patient/parent sets (47 new mutation patients and 20 familial cases), five (7.5%) showed loss of heterozygosity (LOH), indicative of NF1 gene deletion. These five patients did not have severe NF1 manifestations, mental retardation, or dysmorphic features, in contrast to previous reports of large NF1 deletions. All five deletions were de novo and occurred on the maternal chromosome. However, two patients showed partial LOH, consistent with somatic mosaicism for the deletion, suggesting that mosaicism may be more frequent in NF1 than previously recognised (and may have bearing on clinical severity). We suggest that large NF1 deletions (1) are not always associated with unusual clinical features, (2) tend to occur more frequently on maternal alleles, and (3) are an important mechanism for constitutional and somatic mutations in NF1 patients.     

Comparison of treatment of tardive dystonia and idiopathic cervical dystonia with botulinum toxin type A

To compare clinical parameters of patients treated with botulinum toxin type A (BTX) for treatment of idiopathic cervical dystonia (ICD) and for tardive cervical dystonia (TCD), we studied 156 patients (149 with ICD and 7 with TCD) who were treated with serial injections of BTX over 5 years. We hypothesized that patients with TCD and ICD would demonstrate similar improvement in severity scores after treatment with BTX. The diagnosis, dates, dosages, and frequency of BTX injected and severity assessments were recorded into a computerized database. Nonparametric Wilcoxon rank sum and signed-rank tests were used to assess statistical significance. The change in severity scores between the first treatment and last treatment in both groups was not statistically significant (p = 0.4859), indicating similar improvement. The difference in BTX doses was significant (p = 0.0045). ICD patients (n = 149) received an average of 219.8 +/- 63.5 units and those with TCD (n = 7) were treated with an average dose of 287.4 +/- 60.3 units. The average number of days between treatments for individuals with ICD was 142.9 +/- 85.8, similar to that for persons with TCD (144.7 +/- 64.5) (p = 0.6075). Our analysis provides preliminary evidence that the improvement from the administration of BTX for patients with ICD and TCD is similar.     

Botulinum toxin A for hyperkinetic facial lines: results of a double-blind, placebo-controlled study

Although enterotoxins have been implicated in disease states such as food poisoning and toxic shock syndrome, their role in infectious arthritis is not known. To study the arthritogenic properties of toxic shock syndrome toxin 1 (TSST-1), two pairs of S. aureus strains isogenic for TSST-1 production were injected intravenously into healthy Swiss mice. Mice injected with TSST-1-secreting staphylococcal strains developed more frequent and more severe arthritis than did mice inoculated with the isogenic TSST-1-deficient counterparts. Immunohistochemical analysis of arthritic joints revealed an equal number of infiltrating phagocytes in both groups; however, mice inoculated with TSST-1-producing staphylococci had significantly more (P < .01) interleukin-2 receptor-expressing cells in the inflamed synovium than did mice that received the isogenic counterpart. Thus, TSST-1 is a virulence determinant in S. aureus arthritis in mice. The precise mechanism by which this toxin contributes to the development and progression of arthritis needs further investigation.