Nerve injection injury with botulinum toxin

The therapeutic use of botulinum toxin (Botox) is increasing in popularity. Previous studies have shown that various drugs, especially when injected intrafascicularly, can cause major nerve damage. This study evaluates the potential for neurotoxicity of botulinum toxin in a rat sciatic nerve model. Lewis rats were randomly assigned to one of six groups (n = 10/group). Group 1, 2, and 3 rats received, respectively, an intrafascicular, extrafascicular, and extraneural injection of 50 microl of botulinum toxin (50 UI/ml). Group 4, 5, and 6 rats received 50 microl of 10% phenol as a positive control. Five animals received saline as a negative control. Animals were sacrificed at 2 and 7 weeks. Nerves were harvested and processed for histology and morphometry. Nerves in all botulinum toxin groups retained a normal architecture without cellular infiltration or demyelination. The number and diameter of fibers, the thickness of myelin, and the percentage of neural tissue were comparable with normal controls. Nerves injected intraneurally with phenol presented with severe damage, demyelination, and inflammation at 2 weeks and showed signs of early regeneration at 7 weeks. This study demonstrates that in a rat model, even direct intraneural injection of botulinum toxin caused no damage. This information should encourage the reconstructive surgeon to consider broader applications of this drug.     

Intrasphincteric injection of botulinum toxin is effective in long-term treatment of esophageal achalasia

We investigated the long-term efficacy and safety of intrasphincteric injections of botulinum toxin (100 U) in 57 patients with esophageal achalasia. One month after treatment, 50 patients had improved (88%); both symptom score and LES pressure were significantly reduced (P < 0.001). After a mean follow-up of 24+/-15 months (range 6-48), 43 patients (75%) are still in remission, although repeat injections of toxin were needed to achieve a stable effect on symptoms.     

Treatment of Frey's syndrome with botulinum A toxin

A 74-year-old woman suffered from severe gustatory sweating and flushing of the preauricular skin following parotidectomy (Frey's syndrome). She was treated with intracutaneous botulinum A toxin injections in the affected skin area. Minor's test was used to determine the extent of the affected area. Within one week, the symptoms disappeared. After three weeks, Minor's test was repeated and showed minimal residual hyperhidrosis. These small areas were treated again. No side effects were noted. At follow-up one year later, the patient was free of symptoms.     

Extensor truncal dystonia: successful treatment with botulinum toxin injections

An alternative method of determining the integrated input function, necessary in the quantitative [18F]fluorodeoxyglucose (FDG) autoradiographic model, has been developed. Using erythrocytes as reference tissue, researchers require only one blood sample after injection of FDG to obtain the integrated input function. METHODS: The amount of FDG-6-PO4 in the erythrocytes is proportional to their exposure to FDG, that is, the integrated input function. Free FDG is removed by washing the erythrocytes twice. Inter- and intraindividual differences of the metabolic rate of erythrocytes are corrected for by an in vitro incubation with a known amount of FDG. RESULTS: Validation of the proposed method was done by correlating the integrated input function, based on the glucose metabolism of the erythrocytes, to the integrated input function obtained by multiple venous blood samples. The new method provides the integrated input function with an accuracy better than +/-8%. CONCLUSION: By using erythrocytes as a reference tissue, researchers can determine the integrated input function in the quantitative FDG autoradiographic model with an accuracy sufficient for clinical PET studies. The simplicity of the method also makes it suitable for FDG studies on small children. With two samples, the method can also be used for a simplified graphical Patlak analysis.     

Interventional neuropediatrics: treatment of dystonic and spastic muscular hyperactivity with botulinum toxin A

Therapeutic effect of botulinum toxin A was studied in a group of pediatric patients (n = 28) aged between 6 months and 18 years. The patients were diagnosed with cervical dystonia (n = 6), adductor spasm of the hip (n = 8), spastic drop foot (n = 7) and various other focal motor problems associated with spastic muscular hyperactivity (n = 7). The mean dose of botulinum toxin A (Dysport) used to inject into the affected muscle was 22 U/kg body weight. Reduced muscular hyperactivity with a significant increase in joint mobility was achieved for dystonic (p < 0.0001) as well as for spastic conditions in patients with adductor spasm (p < 0.0002). For these patients the improved joint mobility represented a significant benefit for both daily activities and nursing care. Local paresis and local hematoma were observed in 1/28 and 1/28 patients, respectively; 1/28 patients developed a secondary non-response. However, apart from these side effects, no other adverse reactions to botulinum toxin A treatment were recorded during the treatment and observation period (12-64 months). Our results suggest that botulinum toxin A represents an effective and safe therapeutic substance for the treatment of pediatric patients suffering of focal motor problems due to dystonic or spastic muscular hyperactivity.     

Endoscopic injection of botulinum toxin for biliary sphincter of Oddi dysfunction

A 66-year old man was admitted to our hospital because of vomiting, diarrhea and progressive dyspnea. Acute respiratory distress syndrome (ARDS) due to bilateral pneumonia was diagnosed and he was also in septic shock. The patient had a history of partial hepatectomy for hepatoma, and suffered from liver cirrhosis. Emergency bronchoalveolar lavage (BAL) revealed abundant gram-positive cocci and polymorphonuclear leukocytes in the collected sample. Blood culture revealed corynebacterium. Treatment consisted of mechanical ventilation and administration of fluids, effective antibiotics, and high-dose methylprednisolone (MPS). MPS was administered from the onset of ARDS with a starting dose of 1,000 mg, which was gradually reduced to 60 mg over 8 days. Pulmonary infiltrates shown on the chest X-ray film were alleviated, and arterial blood gas data rapidly improved. The patient was successfully extubated on the 10th hospital day, and discharged on the 30th hospital day. Serial BAL and plasma levels of inflammatory cytokines decreased rapidly in parallel with the improvement of the patient's clinical condition. This is a case report of severe bacterial pneumonia that was successfully treated with effective antibiotics and high-dose MPS for several days from the onset of ARDS.     

Comparison of two injection techniques using botulinum toxin in spastic hemiplegia

This study sought to test the hypothesis that injections of botulinum toxin type A (BTX-A) at the mid belly of the gastrocnemius muscle in spastic hemiplegic adults produce superior clinical results to proximal injections directed toward the muscular origin. We designed a randomized, double-blind, placebo-controlled intervention study at a university tertiary care setting. Seventeen subjects with chronic spastic hemiplegic gait were enrolled from a volunteer community sample; time range from acute neurologic insult was 0.75 to 31 yr; age range was 19 to 71 yr; gender consisted of 11 men and 4 women; diagnoses were 12 patients with stroke, 2 with traumatic brain injuries, and 1 with a brain tumor. Two subjects were withdrawn from the study because of (1) acute vascular occlusion before intervention and (2) noncompliance with follow-up visits. After baseline measurements, subjects were injected with 50 units of BTX-A (volume, 0.5 cc) into the medial or lateral gastrocnemius: (1) proximally at one site near the muscular origin; (2) distally at three sites along the mid belly. We measured outcome using the Fugl-Meyer score, Ashworth scale, ankle range of motion, and a timed 50-ft fastest walk. No outcome measures showed a significant effect attributable to site of injections. Confounding variables included physical therapy and varying duration of illness in the study cohort. We conclude that the results failed to support the hypothesis that BTX-A injections at the mid belly of the gastrocnemius produced superior functional improvements to injections located near the muscular origin using localization techniques described. Additional research comparing more precise localization methods for BTX-A injections might further establish the importance of electromyographic guidance using BTX-A in management of spasticity.     

Treatment of spasticity with botulinum toxin

Spasticity is a velocity-dependent pathologic increase in muscle resistance to stretch, and occurs in a variety of neurologic disorders. We report our controlled open study using botulinum toxin A for treatment of adductor spasticity in five patients with advanced multiple sclerosis. Clinical evaluation of spasticity and stiffness of joints is based on the Ashworth Scale and grade of passive abduction. Three patients showed no response; the two others experienced an excellent and longlasting effect. We also describe briefly the different spastic conditions where this treatment has been used successfully.     

Use of botulinum toxin type F injections to treat torticollis in patients with immunity to botulinum toxin type A

Fifteen patients with torticollis who had been treated with repeated injections of botulinum toxin type A (botox A) developed antibodies to the toxin. This resulted in loss of benefit in the 13 patients who had improved with botox A injections and failure to develop muscle atrophy after injection in all 15 patients. Patients were then injected with botulinum toxin type F (botox F) in the same muscles that had been injected with botox A. Ten of the 15 improved after botox F injections, including 9 of the 12 patients who had improved with type A toxin. Six of 9 patients with pain had improvement in pain after botox F injections. Patients reported similar improvement with type F and type A toxins, but duration of benefit was approximately 3 months with type A and approximately 1 month with type F. Botox F is an effective treatment for torticollis in patients who are immune to botox A. The usefulness of type F toxin, however, is limited by short duration of benefit.     

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.     

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.     

Treatment of ventricular dysphonia with botulinum toxin

Ventricular dysphonia, traditionally known as dysphonia plica ventricularis, is a voicing disorder in which the false vocal folds are used as a vibratory source in addition to or instead of the true vocal folds. Traditional treatment of ventricular dysphonia has been voice therapy, which may be slow to produce results if the false fold activity masks an underlying problem of the true folds, is long standing, or has produced hypertrophy of the supraglottic structures. We present seven cases of ventricular dysphonia treated with botulinum toxin injection into the false vocal folds followed by speech therapy. The addition of botulinum toxin to the treatment regimen speeds recovery of normal voicing and allows immediate evaluation of dynamic true vocal fold function by the treating professional.     

Treatment of hemifacial spasm with botulinum toxin

We injected botulinum toxin to treat hemifacial spasm, and investigated the effects and the patient's impression of this treatment. Average duration of improvement lasted about 3.5 months in both the initial treatment group and the recurrent group. However the patients in the recurrent group received fewer units of botulinum toxin than those in the initial treatment group. Except for local paralysis that disappeared within a month, there were very few complications. Most patient were satisfied with this treatment. We conclude that the treatment of hemifacial spasm with botulinum toxin is both simple and useful.     

Therapeutic use of botulinum A toxin in neurology

The highly potent neurotoxins produced by Clostridium botulinum lead to botulism when ingested in appreciable amounts. However, botulinum toxin injections delivered intramuscularly in very small quantities can produce a therapeutically intended focal paresis while producing only negligible local or systemic side effects. Over the past several years, various neurological disorders, especially those involving increased muscle tone and/or abnormal movements, have been successfully treated with local botulinum A toxin injections. The success of this method has led to a general change in the management of blepharospasm, torticollis spasmodicus, hemifacial spasm, and other disorders. Treatment is usually effective for 4 to 12 weeks; if symptoms recur, the injections can be repeated over a period of several years, usually with the same success. Side effects depend on the site of the injections, and are rare at the optimal dosage and always reversible. For optimum therapeutic results, this treatment must be restricted to specialized centers.