Quantifying how location and dose of botulinum toxin injections affect muscle paralysis

Despite the widespread use of botulinum toxin to treat muscle dystonias, no method exists to quantify muscle paralysis in either human or nonhuman models. In this study we examined how the location, dose, and volume of botulinum injection affects paralysis in the rat tibialis anterior muscle. Paralysis was quantified by electrically stimulating the nerve to the tibialis anterior and then staining sections of the muscle for glycogen. The areas of glycogen-containing fibers represented regions of botulinum action. The results showed that the most important injection technique is to inject botulinum directly into the motor endplate region of a muscle. Injections only 0.5 cm from the motor endplate resulted in a 50% decrease in paralysis. Increases in dose increased paralysis, however, some of that increase was simply due to the increased volume of injection. Thus, delivering toxin in small volumes near the MEP band of a muscle should produce the most effectiveparalysis. © 1993 John Wiley & Sons, Inc.     

Clinical correlates of response to botulinum toxin injections.

We studied 242 patients with cervical dystonia who had adequate follow-up after botulinum toxin injections to determine which clinical variables had a predictive value in the treatment outcome. Twenty-one patients (16%) categorized as nonresponders were compared with 113 patients (47%) considered to be definite responders. On average, the nonresponders had symptoms for 14 years longer than responders. Seventy-eight of 100 patients with complications were female compared with 54% of 190 patients without complications. In addition, patients with complications weighed less than those without complications. Both findings suggest that the occurrence of complications is related to smaller mean neck muscle mass. Botulinum toxin antibodies were detected in 35.7% of the nonresponders tested and in none of the responders. This comprehensive analysis of outcome variables leads us to conclude that patients with a long duration of dystonia before their first botulinum toxin injection respond less well than those with a short duration of symptoms, that some patients lose their responsiveness because of the development of blocking antibodies, and that women are more likely to develop complications, such as dysphagia and neck weakness, than are men.     

Writer's cramp: treatment with botulinum toxin injections

Twelve patients with writer's cramp were treated with injections of botulinum toxin. The overactive muscles were identified by clinical observation of the subjects while they were writing. Repeated injections were given at 2-week intervals until the optimal response was obtained. Eleven patients reported some benefit, which was considered by seven to be significant. Eight of the 10 patients who had pain reported moderate to significant relief. Five patients had local complications, consisting of disabling weakness of target or neighbouring muscles. These preliminary results suggest that this treatment can be successfully applied to many patients with writer's cramp without performing complex electromyographic recordings while the patients are writing.     

Manual needle placement: Accuracy of botulinum toxin a injections

Introduction: Electrophysiological or ultrasound guidance can facilitate botulinum toxin A (BoNt‐A) injection accuracy, but clinical landmarks and palpation are often used for superficial muscles. We evaluated the accuracy of manual needle placement in the gastrocnemius muscles (GC) guided only by anatomical landmarks and palpation. Methods: Bilateral limbs from 30 cadavers were used to evaluate ink injection into the GC. One anatomist and one orthopedic surgeon verified the accuracy of manual needle placement postinjection by calf muscle dissection. Injection was considered a failure if the ink was not located in the head of the target GC. Results: One hundred twenty‐one practitioners were evaluated. Fifty‐two injections were successful (43%), and 69 failed (57%). This result was unrelated to injector experience (P = 0.097). Conclusions: Our findings show a poor success rate, regardless of injector experience. Therefore, muscle palpation and anatomical landmarks are insufficient to ensure the accuracy of BoNt‐A injections, even for large, superficial muscles. Muscle Nerve 46: 531–534, 2012     

Botulism after intragastric botulinum toxin injections for weight reduction

Although—considering the risk–benefit ratio—botulinum neurotoxin A (BoNT/A) is unequivocally recommended to treat severe neurological diseases such as dystonia, this has not yet been determined for its endoscopic intragastric injection aimed at weight reduction in obesity. However, severe adverse effects of intragastric BoNT/A had not yet been reported, prompting some European countries to endorse its (off-label) use and treat patients transnationally. We here present three cases of botulism after intragastric BoNT/A injections for obesity treatment in a Turkish hospital. Patients presented with cranial nerve affection, bulbar symptoms, and descending paresis, and benefited from treatment with BoNT antitoxin and pyridostigmine. We assume that iatrogenic botulism was induced by overdosing in combination with toxin spread via the highly vascularized gastric tissue. Of note, within a few weeks, more than 80 cases of iatrogenic botulism were reported across Europe after identical intragastric BoNT/A injections. These cases demonstrate the risks of BoNT/A injections if they are not applied within the limits of evidence-based medicine. There is a need for international guidelines to define the indication and a safe dosing scheme, especially in the context of medical tourism.     

Treatment of spasmodic torticollis by local injections of botulinum toxin

Injections of botulinum toxin into the main cervical muscles responsible for abnormal posture and movements in spasmodic torticollis reduced pain and attenuated dystonia for a period of 2 months on average. After several sessions 9 out of 36 patients (25 p. 100) felt they had improved by at least 50 percent, 16 (44 p.100) by 50 to 75 percent, and 6 (17 p. 100) by more than 75 percent. There were six failures.     

Treatment of spasmodic torticollis with local injections of botulinum toxin

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

Isolated high-frequency jaw tremor relieved by botulinum toxin injections.

Jaw tremor can be seen as a component of various neurological disorders such as essential tremor, Parkinson's disease, dystonia, branchial myoclonus, hereditary geniospasm, task-specific tremor, and Whipple's disease, as well as in normal situations such as shivering, and subclinical physiological jaw tremor. In most of these conditions, the jaw tremor is usually associated with tremor or other abnormal involuntary movements affecting additional body parts, and its frequency is lower than 12 Hz. Schrag and colleagues reported a patient with a high-frequency idiopathic jaw tremor, and they speculated it could be related to orthostatic tremor affecting the masseter muscles. We encountered a similar patient with intermittent rapid focal jaw tremor that was successfully treated with botulinum toxin injections to the masseters.     

A strategy for managing flu-like symptoms after botulinum toxin injections

Journal of Neurology -     

Flexor digitorum superficialis: Locations of individual muscle bellies for botulinum toxin injections

Twenty-two Flexor Digitorum Superficialis (FDS) muscles from 18 cadavers were dissected to find the “Optimal Injection Site” (OIS) for botulinum toxin injections to individual bellies of FDS. Coordinates are given as a percentage of the distance along a landmarking line from the medial epicondyle to the pisiform and in millimetres (mm) lateral to it. The OIS were: FDS2: 72%, 14 mm; FDS3: 54%, 17mm; FDS4: 49%, 7mm; FDS5: 76%, 6mm. OIS measurements guide the electromyographer to localize the targeted muscle belly. © 1997 John Wiley and Sons, Inc. Muscle Nerve 20: 1041–1043, 1997     

A case of painless arms/moving fingers responsive to botulinum toxin a injections

Painless arms/moving fingers is a rare variant of the painful limbs/moving extremities syndrome (PLME) characterized by slow involuntary movements of the toes or fingers. Its typical form is associated with limb pain. We report the first case of painless arms/moving fingers and describe its favorable response to botulinum toxin A injections. The presence of dystonic symptoms in our case argues in favor of a possible implication of a dystonic mechanism in at least some cases of PLME.     

Functional outcome of botulinum toxin A injections to the lower limbs in cerebral palsy

We evaluated gross motor function following botulinum toxin A (BTX-A) injections in the lower limbs of children with spastic cerebral palsy in a randomized clinical trial, using a cross-over design. Forty-nine children (24 males, 25 females, age range 22 to 80 months) were randomly allocated to two groups: group 1 received BTX-A and physiotherapy, and group 2 received physiotherapy alone for 6 months. At the end of this period, group 2 received BTX-A and physiotherapy and group 1 continued with physiotherapy alone. Assessment measures were the Gross Motor Function Measure (GMFM), the Vulpe Assessment Battery (VAB), joint range of movement, the Modified Ashworth Scale, and a parental questionnaire. Sustained gains in gross motor function were found in both groups of children but the only additional benefit found in group 1 was a significant increase in fine motor rating on the VAB. By contrast, parents rated the benefit of treatment highly. It is likely that assessment at 3 and 6 months post injection was too late to demonstrate peak gross motor function response and that changes in GMFM are not sustained over 6 months with a single dose. Further studies should investigate changes over shorter time periods and consider covariables such as BTX-A dosage, number of injection sites, and the role of repeated injections combined with other interventions such as casting.