The effect of peritoneal air exposure on postoperative tumor growth

Botulinum toxin A has been used to treat wrist and finger spasticity mainly through injection of the forearm flexor muscles. This case study describes its first reported use in managing spastic lumbricals of the hand. A 19-year-old male had significant flexion deformity and hypertonicity of the left wrist and hand, particularly the second through fifth metacarpophalangeal joints, after traumatic brain injury. By using the 0-4 Ashworth scale, spasticity of the lumbricals across the second to fourth metacarpophalangeal joints was rated 2, with persistent clonus of the finger flexors as confirmed by electromyography to the middle and ring fingers, even after botulinum toxin A injection of the flexor digitorum sublimis and profundus muscles. By using the electromyography-guided technique, botulinum toxin A was injected into the first lumbrical of the index finger (12 units), second and third lumbricals of the middle and ring fingers, respectively (15 units each), and fourth lumbrical of the little finger (10 units). At follow-up, clinical and electromyographic examination revealed a significant reduction in tone and clonus of the injected lumbricals. Ashworth scores of the lumbricals from the index to little finger improved to 1. Botulinum toxin A injection of the lumbricals can be beneficial in managing spasticity of these muscles. It is well tolerated and effective at doses of 10 to 15 units. Lumbrical injection of botulinum toxin A is a useful adjunct in our percutaneous armamentarium for managing the spastic hand.     

Botulinum toxin restores presynaptic inhibition of group Ia afferents in patients with essential tremor

We studied the effect of botulinum toxin A injection on the abnormal presynaptic phase of reciprocal inhibition between forearm antagonist muscles in patients with essential tremor. Ten patients with essential tremor were investigated before and 1 month after botulinum injection. Reciprocal inhibition was studied by conditioning the H reflex in forearm flexors with a radial-nerve stimulus delivered at a range of time intervals. Botulinum toxin produced a significant functional improvement in tremor (about 20%). Before botulinum toxin injection, patients had a reduced presynaptic phase of reciprocal inhibition. After botulinum toxin this phase was significantly more pronounced. The normal early disynaptic phase of reciprocal inhibition was normal before and after botulinum treatment. Although botulinum treatment reduced the size of the H reflex and the M wave to a similar extent, it left the H/M ratio unchanged. These findings show that botulinum toxin treatment restores presynaptic inhibition between forearm antagonist muscles. The results are also consistent with botulinum toxin having a beneficial effect in patients with essential tremor. Both effects probably depend upon the toxin's concurrent action on the extrafusal and intrafusal motor end-plates, the latter resulting in decreased spindle afferent input to the spinal cord.     

Preliminary experience with intrasphincteric botulinum toxin for persistent constipation after pull-through for Hirschsprung's disease

Although most children who have Hirschsprung's disease have an excellent result after pull-through surgery, some experience persistent constipation caused by "internal sphincter achalasia." Anal myectomy has been advocated for this problem, but it results in permanent injury to the sphincter and is not universally effective. Botulinum toxin has been safely used to selectively and reversibly weaken a variety of voluntary muscles and sphincters in both adults and children. Injection of botulinum toxin into the internal anal sphincter (IAS) should theoretically produce the same functional result as anal myectomy without permanent sphincter injury. Four children aged 4 to 8 years presented with persistent constipation after a pull-through procedure for Hirschsprung's disease. Two had associated encopresis, both of whom had previous myectomies. The authors performed four-quadrant intrasphincteric botulinum toxin injection (total dose, 15 U). Resting IAS pressure decreased in all children 4 to 8 weeks after injection. Patients have been followed up for 7 to 9 months. One child (with Down's syndrome) remained symptomatically unchanged. The other three families reported significant improvement in bowel function in their children. In two of these, there was a return of symptoms 6 months after injection; one child underwent reinjection with good results. Postinjection incontinence occurred in three children, but resolved after several weeks in the one who did not have encopresis before botulinum toxin injection. These preliminary results suggest that botulinum toxin may represent a less invasive alternative to anal myectomy for children who have severe constipation after surgery for Hirschsprung's disease. If myectomy is contemplated, botulinum toxin may also be useful as a means of predicting which children may benefit.     

Repeatedly successful closure of the larynx for the treatment of chronic aspiration with the use of botulinum toxin A

Botulinum toxin A was used preoperatively to temporarily paralyze the intrinsic laryngeal muscles to hinder movements during the healing period after operation. In addition, toxin was injected into the cricopharyngeal muscle to allow a better passive drainage of the saliva into the esophagus. We treated six patients. Three suffered from chronic aspiration problems after multiple lower cranial nerve lesions, and three patients were apallic (after stroke and major brain injury). Two weeks before scheduled operation, we injected the toxin into the posterior cricoarytenoid muscles, the aryepiglottic muscles, and the vocalis muscle on both sides, as well as the cricopharyngeal muscle. The amount of injected toxin varied between 1.0 and 1.4 mL, equal to 200 to 280 units of botulinum toxin A (Dysport). After a complete palsy of these muscles (controlled by direct electromyography), a closure of the larynx was performed. After laminotomy and exposure of the intralaryngeal structures, the false vocal cords were mobilized and adapted with sutures. Because involuntary movements of the intralaryngeal musculature were absent, primary healing without complications occurred in all cases. Aspiration and related complications disappeared in all patients. In addition, the intensity of patient care could be considerably reduced. Preoperative use of botulinum toxin A allows sufficient laryngeal closure. This procedure is especially useful in the treatment of children and young adults, preserving the ability of later speech rehabilitation because of the return of voluntary movements of the intrinsic laryngeal muscles 6 months after the injection. Furthermore, this technique, as minimal surgical intervention, can be performed in high-risk patients.     

What''s new in colorectal cancer screening?

BACKGROUND/AIM: Patients with thyroid eye disease with upper eyelid retraction often develop overaction of the accessory muscles of eyelid closure, the glabellar muscles corrugator supercilii and procerus. The resultant glabellar furrowing (frown lines) contributes to the typical thyroid facies. The aim of this study was to evaluate the use of botulinum toxin A reversible chemodenervation of the glabellar muscles as adjunctive treatment in the rehabilitation of patients with thyroid eye disease. METHODS: 14 patients (13 females) ages 39-76 years (mean 52) with inactive thyroid eye disease and associated medial eyebrow ptosis and prominent glabellar frown lines were recruited. All patients had a history of upper eyelid retraction. Each patient was treated with a single botulinum toxin injection (Dysport 0.2 ml, 40 units) into each corrugator supercilii and sometimes procerus muscles as an outpatient procedure. The effectiveness and acceptability of the treatment was assessed clinically and from a patient questionnaire. RESULTS: The injections were tolerated by 13/14 (93%) patients. There was resultant flattening of the glabellar region and improvement of medial eyebrow contour in all patients, with onset of paralysis within 1 week. All patients reported a subjective improvement in appearance. Side effects included one patient (7%) with reversible partial ptosis. The beneficial effect lasted 4-6 months, with a gradual return of function. Repeat treatment was indicated where there was persistent upper eyelid retraction and protractor overaction. CONCLUSION: Botulinum toxin A chemodenervation of the glabellar muscles in these patients was effective and acceptable. Chemodenervation should be considered in the rehabilitation of patients with thyroid eye disease where there is upper eyelid retraction and overacting protractors resulting in a thyroid frown. Once the eyelid retraction has been successfully treated by surgery, the need for further glabella muscle chemodenervation is considerably reduced.     

Inflammatory pseudotumor of the abdomen: report of a case

BACKGROUND: Cosmetic denervation of hyperfunctional facial lines using botulinum toxin (Botox, Allergan, Inc., Irvine, CA) has gained growing popularity over recent years. Understanding the clinical use and effects of botulinum toxin requires a thorough understanding of the muscular anatomy of the treatment areas. OBJECTIVE: The purpose of this article is to review the anatomy of the frown, forehead, and periocular regions. Function of individual muscles is discussed to understand proper injection technique. CONCLUSIONS: The anatomy of the frown, forehead, and periocular regions is complex. Individual muscles are tightly intertwined and treatment of one anatomic region may affect many different muscles. A complete understanding of the anatomy of the upper face is essential to ensure proper injection technique, safe and predictable results as well as anticipating complications.     

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 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.     

Transoral electromyographic recordings in botulinum toxin-injected rat larynges

Objective assessment of muscle function following botulinum toxin injections in laryngeal muscles is difficult in human subjects. We developed a rat laryngeal model for the study of botulinum toxin injection. A new laryngoscopic technique has made it possible to observe the rat larynx endoscopically and to obtain electromyographic measurements during and after injection of toxin. The electromyographic interference pattern, fibrillation potentials, and vocal fold movement were used for analyzing dose and volume effects of injected toxin. We conclude that the lowest dosage able to produce the maximal duration of functional laryngeal impairment is 0.07 U in a volume of 0.4 microL. This model will enable us to obtain physiologic and histologic parameters that can be used to assess the selection of optimal treatment regimens with botulinum toxin for the treatment of patients with spasmodic dysphonia.     

Outcome of Perthes'' disease in unselected patients after femoral varus osteotomy and splintage

PURPOSE: To study the incidence, cause, recovery time, and prevention of diplopia following subcutaneous injection of botulinum A toxin for the treatment of facial spasms. METHODS: Patients who experienced diplopia after botulinum A toxin injections had their deviations examined in detail. When the muscle that caused diplopia was identifiable, the injection closest to that muscle was omitted in the next treatment in an attempt to prevent diplopia. RESULTS: Of 250 patients receiving about 1500 sets of injections, 25 (1.7%) incidents of diplopia occurred in 10 patients. Excluding two patients who declined further treatment after having diplopia on their first botulinum A toxin treatment, seven of the remaining eight patients had multiple incidents of diplopia. The most common pattern of diplopia was "uncertain diagnosis." The most common identifiable cause of diplopia was paresis of the inferior oblique muscle. Omission of the injection into the central portion of the lower eyelids in the next treatment prevented recurrence of diplopia in only one of the four patients. No significant correlation between botulinum A toxin doses injected and times to recovery was noted. CONCLUSIONS: Diplopia following botulinum A toxin treatment is uncommon. Seven patients (3% of patients studied) had 22 episodes of diplopia (88% of episodes). When diplopia occurs, it tends to recur on reinjection, sometimes with a prolonged recovery time. This response may not be dose dependent. The extraocular muscles of some patients may be more susceptible to chemodenervation than others, or botulinum A toxin may diffuse to extraocular muscles more easily in some patients than in others.     

Ethics in clinical research: searching for absolutes

Recently botulinum toxin has been used with increasing frequency as a safe and effective treatment for many previously refractory conditions associated with excessive muscle activity. The indications for use of botulinum toxin injection continue to expand. This report describes the case of an 83-year-old woman with a history of diabetes mellitus and lumbar spinal stenosis who developed a severe focal dystonia of the left great toe, such that the toe maintained the extended position. Functionally, the resultant deformity prevented the patient from wearing shoes. In addition, the patient had significant pain in the left great toe. Under needle electromyographic localization, 50 units of botulinum toxin were injected into the left extensor hallucis longus muscle. Two weeks after the injection the patient was symptom free and could place her left foot into a shoe. Seven months later, she remained symptom free. This case illustrates that localized injection of botulinum toxin to a specific lower limb muscle can effectively result in decreased muscle activity and functional improvement.     

Mechanism of action, clinical indication and results of treatment of botulinum toxin

Botulinum toxin, the most potent of the neurotoxins, produces paralysis by blocking presynaptic release of the neurotransmitter (acetylcholine) at the neuromuscular junction, with reversible chemical denervation of the muscle fibre, thereby inducing partial paralysis and atrophy. Because chemical denervation is reversible, botulinum toxin has temporary effects, the muscle being progressively reinnervated by nerve sproutings. Type A botulinum toxin (Bix-A) is available under two dosage forms: Botox and Dysport. Although the initial clinical indication was strabismus, subsequent studies have demonstrated the efficacy of Btx-A, mainly in dystonia, hemifacial spasm and spasticity. However, botulinum toxin has been successfully used in various other clinical indications. In regard to spasticity associated with cerebral palsy, Btx-A is a promising treatment requiring a multidisciplinary approach. Btx-A injections lead to effective reduction of muscle hyperactivity with minor side-effects. They are painless, even though electromyographic guidance may be required for the injection of deep muscles. However, the production of antibodies to Btx-A may compromise the effect of long-term treatment.     

Temporary luminal arteriotomy seal for bypass grafting

OBJECTIVE: To compare the effects of botulinum toxin on static and dynamic aspects of eye movements, and thereby elucidate the mechanisms of its action on eye muscles. BACKGROUND: Laboratory evidence indicates that static alignment and saccades are subserved by different extraocular muscle fiber types, and botulinum toxin may cause specific dysfunction of the fibers controlling static alignment. Diplopia is a well-known side effect of periorbital botulinum toxin injections in humans, and may be a clinical correlate of the laboratory findings. METHODS: Search coil recording of eye movements was performed in one patient with systemic botulism, and in three patients with diplopia following periorbital injection of botulinum toxin A. RESULTS: In the patient with acute botulism, eye movement alignment, range, and saccadic velocity profiles were abnormal. In three patients with iatrogenic diplopia, static alignment was abnormal but movement range and saccadic velocities were within normal limits. Edrophonium improved the range of movements and saccadic velocities in the patient with systemic botulism but was ineffective in reversing ocular misalignment in the one iatrogenic patient to whom it was administered. CONCLUSIONS: Precise alignment is subserved by orbital singly innervated muscle fibers, and the effects of botulinum toxin are greatest on these fibers. This predilection is apparent when the toxin dose is very small, as must have been the case in our patients with iatrogenic diplopia. The lack of a response to edrophonium probably reflects structural damage to muscle fibers. In contrast, larger doses of toxin produce an acute dysfunction of all extraocular muscle fiber types, which is responsive to edrophonium and consequently reflects partial blockade at the neuromuscular junction.     

Wound botulism in heroin addiction]

Botulism is a rare disease which usually is caused by preformed botulinum toxin in food. However, this article describes a case of wound botulism in a 29-year-old male heroin addict who developed progressive diplopia, dysphagia and proximal weakness of skeletal limb muscles. He needed mechanical ventilation for two weeks. The clinical diagnosis of botulism was supported by neurophysiological tests. Assays for detection of botulinum toxin and Clostridium botulinum were negative. The patient had not eaten any contaminated food the last two weeks before symptoms appeared, but he had multiple contaminated skin wounds. After treatment with botulinum antitoxins and antibiotics he gradually recovered, and six weeks later he was discharged from hospital in good condition. To the best of our knowledge this is the first case of wound botulism reported in Norway.     

Electromyographic guidance in injecting botulinum toxin

BACKGROUND: Many practitioners involved with the cosmetic applications of botulinum toxin believe that electromyography (EMG) is an invaluable tool in determining the precise locations to inject. Others feel that it is unnecessary and of no value whatsoever. OBJECTIVES: The objective of this paper is to (1) demonstrate the proper technique for usage of the EMG machine, and (2) determine if its use in connection with injection of facial muscles for cosmetic purposes is worthwhile. CONCLUSIONS: The anatomy of the muscles of the face is somewhat variable from person to person. Electromyography can be a valuable adjunct when injecting botulinum toxin for cosmetic purposes by ensuring that the injecting needle is precisely in the muscle, thereby ensuring that the botulinum toxin will have the greatest possible effect.     

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.     

Urinary tract infection: bacterial adhesin and biofilm formation]

Localized botulinum toxin injection disrupts cholinergic transmission and has potential to cause focal dysautonomia. Mucociliary transport and laryngeal secretions are thought to be mediated in part by autonomic, cholinergic transmission. We questioned whether patients who receive Botox injection for adductor spasmodic dysphonia (ADSD) report postinjection symptoms possibly related to altered mucociliary clearance or laryngeal secretions. Medical histories, audiotaped interviews, and symptom ratings were retrospectively examined for 29 patients with ADSD who were followed after one or more Botox injections. Patients had received bilateral, percutaneous Botox injections of 2.5 units using an EMG-guided approach. One or more weeks after injection, four patients reported either burning, tickling, or irritation of the larynx/throat, excessive thick secretions, or dryness. Symptoms recurred with subsequent injections in two patients and were not associated with swallowing difficulty. These symptoms are consistent with, but not diagnostic of, the known effects of botulinum toxin on cholinergic, autonomic transmission.     

Increased acute and chronic mitotic activity in rat laryngeal muscles after botulinum toxin injection

OBJECTIVES: To characterize the acute and chronic cellular effects of botulinum toxin (BT) injection into rat laryngeal muscles. A complete characterization of these effects is important because patients with focal dystonias of the head and neck are commonly treated with BT injection. Further, potential muscular changes in the larynx must be carefully delineated owing to the critical phonatory and airway protective functions of these muscles. STUDY DESIGN: The acute and chronic cellular effects of BT injection were studied using 5'-bromo 2'-deoxyuridine (BrdU) following single and repeated BT injection into rat laryngeal muscles. BrdU is incorporated into mitotically active nuclei such that changes in cell proliferative behavior following BT injection can be monitored. RESULTS: Increased mitotic activity was detected in the tissue samples studied following BT injection. Differences in the times of the peak distribution of BrdU-labeled cells in each laryngeal muscle were observed. This may be related to the diffusion effects of BT. Prolonged muscle fiber changes, including splitting, were also observed as the result of repeated BT injection. CONCLUSIONS: The results of this study suggest that BT may induce a proliferative response in muscle tissue.     

Muscle fiber atrophy in leg muscles after botulinum toxin type A treatment of cervical dystonia

Previous electrophysiologic studies on the effects of local injections of botulinum toxin type A (BTX-A) have indicated impaired neuromuscular transmission in distant muscles. To further study possible distant effects of repeated BTX-A injections, we obtained percutaneous muscle biopsies of the vastus lateralis muscle from 11 patients with cervical dystonia. We examined the biopsies with histopathology and morphometry, and compared them with age-matched healthy controls. There was an increased frequency of angular atrophic type IIB fibers in the patient group, and the mean size of IIB fibers was significantly smaller (p < 0.05). In addition, there was a negative correlation between accumulated dose of botulinum toxin and relative size of type IIA fibers (p < 0.05). We postulate that the observed atrophy is due to distant effects of botulinum toxin causing progressive denervation-like changes in non-treated muscle. This observation calls for further, prospective studies of the long-term effects of the treatment.     

Posttraumatic cervical dystonia

Posttraumatic cervical dystonia has been described as a distinct syndrome with some similarities to idiopathic nontraumatic cervical dystonia (torticollis). We describe five patients in whom cervical dystonia developed immediately after relatively mild trauma to the neck. Four of the five patients had persistent contractions of all cervical muscles including the trapezius muscles, which almost completely prevented motion of the neck and resulted in muscle hypertrophy. The condition persisted unabated in all patients for the entire period of follow-up (duration, 1 1/2 to 3 years). Pharmaceutical interventions, which had been used previously for idiopathic nontraumatic cervical dystonia, failed to benefit these patients. Two patients who received injections of botulinum toxin had no more than mild benefit. Selective denervation was inapplicable because of the widespread involvement of all cervical muscles in all but one patient. Physical therapy was essentially ineffective. Because of the unusual features and possible medicolegal setting, clinicians may tend to diagnose this condition as a psychogenic disorder or litigation-oriented behavior. The clinical picture, however, is consistent with an organic dystonia that may render the patient functionally and occupationally disabled.