Secondary nonresponsiveness to botulinum toxin A in cervical dystonia: the role of electromyogram-guided injections, botulinum toxin A antibody assay, and the extensor digitorum brevis test.
ABSTRACT We studied 20 patients with cervical dystonia who had started to respond poorly to botulinum toxin A (BTXA) injections after an initial good response. All patients had extensor digitorum brevis (EDB) tests performed in addition to BTXA immunoprecipition assay (IPA) and mouse bioassay (MBA) antibody testing. The patients were reexamined and then treated with carefully placed electromyogram (EMG)-guided BTXA. Nine patients had a good clinical response to EMG-guided injections and all of these patients showed an obvious decrement on the EDB test. All were BTXA blocking antibodies (Abs)-negative via IPA and MBA (apart from one patient who had low BTXA antibodies titers using IPA but no antibodies by MBA). In the other 11 patients, there was a poor clinical response to EMG-guided BTXA injections. Seven of these 11 had small EDB decrement and BTXA antibodies using IPA, suggesting resistance to BTXA. Of the remaining four patients, two had obvious EDB decrement and low antibody titers via IPA (one of them had no antibodies via MBA), while the other two patients showed obvious decrement on the EDB test and no antibodies via IPA. This study shows that the EDB test correlates better with the clinical response than the antibody assays and that EDB decrement does not always correlate quantitatively with the BTXA antibody titers. In patients with secondary nonresponsiveness, it is recommended that an EDB test is the initial investigation of choice. In those patients where the EDB test does not demonstrate resistance to BTXA, a reexamination of the patients and carefully placed injections under EMG guidance may improve results.
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ABSTRACT: The aim of this systematic review was to determine whether botulinum neurotoxin (BoNT) reduce spasticity or improve function in adult patients after stroke. Eleven double-blind randomized placebo-controlled trials met inclusion criteria. They encompassed 782 patients, 767 (98%) of whom received BoNT/A, and 15 (2%) BoNT/B. Most studies used the Ashworth scale as primary outcome measure. Differences between treated and control groups were assessed as categorical or continuous comparisons. The overall effect on upper limb spasticity was in favor of BoNT/A. A significantly higher number of patients had a reduction of upper limb spasticity at 4-week and 8-week evaluations in the treatment group compared with placebo. Mean changes in joint spasticity revealed improvement 3 to 6 weeks and 9 to 12 weeks after treatment. There were insufficient data to establish BoNT/A efficacy on lower limb spasticity or the effect of BoNT/B on the upper and lower limbs. Because of inconsistency and heterogeneity of the available data, it was not possible to perform a meta-analysis on disability and patients' reported outcomes. There was an overlapping safety profile between the treatment and the placebo groups. BoNT/A reduces upper limb spasticity in patients post-stroke, but the improvement in functional ability remains to be established. This gap needs to be filled by new studies to assess the effect of BoNT in the context of multidisciplinary patient management.Movement Disorders 03/2009; 24(6):801-12. · 4.51 Impact Factor
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ABSTRACT: OBJECTIVES: to provide a revised version of earlier guidelines published in 2006. BACKGROUND: primary dystonias are chronic and often disabling conditions with a widespread spectrum mainly in young people. DIAGNOSIS: primary dystonias are classified as pure dystonia, dystonia plus or paroxysmal dystonia syndromes. Assessment should be performed using a validated rating scale for dystonia. Genetic testing may be performed after establishing the clinical diagnosis. DYT1 testing is recommended for patients with primary dystonia with limb onset before age 30, and in those with an affected relative with early-onset dystonia. DYT6 testing is recommended in early-onset or familial cases with cranio-cervical dystonia or after exclusion of DYT1. Individuals with early-onset myoclonus should be tested for mutations in the DYT11 gene. If direct sequencing of the DYT11 gene is negative, additional gene dosage is required to improve the proportion of mutations detected. A levodopa trial is warranted in every patient with early-onset primary dystonia without an alternative diagnosis. In patients with idiopathic dystonia, neurophysiological tests can help with describing the pathophysiological mechanisms underlying the disorder. TREATMENT: botulinum toxin (BoNT) type A is the first-line treatment for primary cranial (excluding oromandibular) or cervical dystonia; it is also effective on writing dystonia. BoNT/B is not inferior to BoNT/A in cervical dystonia. Pallidal deep brain stimulation (DBS) is considered a good option, particularly for primary generalized or cervical dystonia, after medication or BoNT have failed. DBS is less effective in secondary dystonia. This treatment requires a specialized expertise and a multidisciplinary team.European Journal of Neurology 01/2011; 18(1):5-18. · 3.69 Impact Factor
Article: Evolution of dose and response to botulinum toxin A in cervical dystonia: a multicenter study.[show abstract] [hide abstract]
ABSTRACT: Botulinum neurotoxin (BoNT) is an effective treatment for cervical dystonia (CD). Long-term changes of several variables, including the dose of BoNT, in these patients is largely unknown. We reviewed the clinical charts of 275 patients with CD treated with BoNT type A (BoNT-A) for at least 5 years since 1989 at ten tertiary centers. The mean dose of BoNT-A per session during the first 5 years of treatment was calculated and the appearance of resistance was noted. The dose of BoNT-A for the whole group showed a significant trend to increase over time (year 1: 180 ± 65 U; year 5: 203 ± 63 U; ANOVA: p < 0.0001). However, when we studied the evolution of the dose of BoNT-A for those patients (n = 49) first injected after 2000 (introduction of current BOTOX preparation in our country), there was no significant increase in dose (year 1: 181.8 ± 75 U; year 5: 181.7 ± 75 U; ANOVA p: ns). A total of 19 patients became secondary nonresponders; all but one of these patients began BoNT-A treatment before 2000. In summary, there is a statistically significant increase of mean dose of BoNT-A per session over time, and this could be explained by the appearance of secondary nonresponders. On the other hand, those patients initially treated after 2000 did not show any statistically significant increase in dose for 5 years. This could be explained by better experience and techniques, fewer immunogenic problems with the current BoNT-A, and also less variability of the dose per vial.Journal of Neurology 01/2011; 258(6):1055-7. · 3.47 Impact Factor