Sudomotor testing predicts the presence of neutralizing botulinum A toxin antibodies

Birklein, Frank; Walther, Dirk; Bigalke, Hans; Winterholler, Martin; Erbguth, Frank

doi:10.1002/ana.10243

Cited by 13 publications

(5 citation statements)

References 28 publications

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“…An alternative explanation for our results might be that BoNT/A interferes with active sudomotor-driven vasodilation in human hairy skin [23]. Sudomotor fibers can be blocked by BoNT/A [4]. Since electrical current used in our experiments also activates peripheral sudomotor fibers and thereby induces local acetylcholine release and axon reflex sweating [45], which is similar in size and spatial extent to the neurogenic flare [33], reduction of flare could readily be explained by blocking these "vasodilatory" sudomotor fibers.…”

Section: S Bont/a Reduces Neurogenic Flarementioning

confidence: 77%

Botulinum Toxin A reduces neurogenic flare but has almost no effect on pain and hyperalgesia in human skin

Krämer¹,

Angerer

Erbguth

et al. 2003

Journal of Neurology

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Botulinum toxin A (BoNT/A) has been used therapeutically to treat muscular hypercontractions and sudomotor hyperactivity. There is increasing evidence that BoNT/A might also have analgesic properties, in particular in headache. In the present investigation we tested the often cited hypothesis that BoNT/A-induced analgesia can be attributed to inhibition of neuropeptide release from nociceptive nerve fibers. In 15 healthy volunteers BoNT/A (5, 10, 20 mouse units BOTOX) or saline (contralateral side) was injected intracutaneously on the volar forearm. On day zero, the day of injection, no further tests were performed. We repeatedly elicited pain, mechanical hyperalgesia and neurogenic flare by transcutaneous electrical stimulation simultaneously on the BoNT/A and saline treated side on day 1, 2, 3, 7 and 14 after injection. Before each session, sweating and local anhidrosis was assessed by iodine starch staining.BoNT/A suppressed sweating as early as from the second day after injection (p < 0.001). The size of electrically induced flare was smaller on the BoNT/A treated arm (BoNT/A side: 21.46 cm(2) +/- 3.58, saline side 24.80 +/- 3.46, p < 0.005) and BoNT/A reduced electrically-induced pain by about 10 % (p < 0.001). However, hyperalgesia to pin-prick and allodynia after electrical stimulation were unchanged. In conclusion our results indicate that peripheral neuropeptide release is attenuated by BoNT/A. In contrast, the analgesic effect of BoNT/A was very limited. Therefore we assume that other than neuropeptide mechanisms must be important for BoNT/A induced pain relief in clinical pain syndromes.

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Section: S Bont/a Reduces Neurogenic Flarementioning

confidence: 77%

Botulinum Toxin A reduces neurogenic flare but has almost no effect on pain and hyperalgesia in human skin

Krämer¹,

Angerer

Erbguth

et al. 2003

Journal of Neurology

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“…QSART This was performed in all subjects in a session before BoNT/B injection to provide baseline values. As there is no di¡erence between right and left legs in healthy subjects (Braune et al, 2001;Birklein et al, 2002), we pooled measurements for both legs (AUC of 534 arbitrary units; range 379^744). After 3 wk, QSART was reduced to 18% of baseline (range 0^64) and even absent in 10 of 15 subjects with BoNT/B doses of 62.5 MU or more (Table I).…”

Section: Resultsmentioning

confidence: 99%

Botulinum Toxin Type B Blocks Sudomotor Function Effectively: A 6 Month Follow Up

Birklein

Eisenbarth

Erbguth

et al. 2003

Journal of Investigative Dermatology

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This study analyzes the suppression of sweat gland activity by botulinum toxin type B. We injected botulinum toxin type B (between 2 and 1000 mouse units subcutaneously) in the lateral side of both lower legs in 15 healthy volunteers. Sweat tests were carried out before botulinum toxin type B injections, and at 3 wk, 3 mo, and 6 mo. We studied focal anhidrosis by iodine-starch staining and by capacitance hygrometry after carbachol iontophoresis, according to the quantitative sudomotor axon reflex test (QSART). Iodine starch staining indicated that a threshold dose of 8 mouse units botulinum toxin type B leads to anhidrotic skin spots (>4 cm2) after 3 wk. Duration of anhidrosis was prolonged for 3 mo when 15 mouse units and for 6 mo when 125 mouse units botulinum toxin type B were injected. The size of the anhidrotic area decreased with time (p<0.001), indicating partial recovery at the edges. After 3 wk, the QSART score had significantly decreased to 18% of baseline and had decreased to zero in most subjects with doses of 62.5 mouse units or more. After 3 mo, the QSART had returned to 91% of baseline in all but one subject and, after 6 mo, recovery of sudomotor function was complete. Analysis by iodine-starch staining and QSART indicated that botulinum toxin type B suppresses sudomotor function effectively, in a concentration-dependent manner.

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“…17,18 In a more complex procedure, additional injections with carbachol (quantitative sudomotor axon reflex test ϭ QSART), sweat chambers, and the iodine-starch reaction as described by Minor were used. 19 The author suggested that the QSART might be powerful enough to estimate the height of BoNT/A-AB titers.…”

Section: Discussionmentioning

confidence: 99%

Ninhydrin sweat test: A simple method for detecting antibodies neutralizing botulinum toxin type A

et al. 2004

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Approximately 5% of patients with cervical dystonia receiving repeated botulinum neurotoxin A (BoNT/A) injections develop secondary loss of treatment benefit. Currently available tests to directly detect neutralizing BoNT/A antibodies (BoNT/A-AB) are either expensive or time consuming. To establish a simple, clinically useful test for antibody detection, we adapted the ninhydrin sweat test (NST). Eighteen dystonic patients with secondary nonresponse and clinically suspected BoNT/A-AB formation were tested for BoNT/A-AB in the mouse diaphragm test (MDT). In addition, the size of the anhidrotic area was determined by the NST 21 days after an intradermal dose of 10 U Dysport into the hypothenar region of the left palm. In nine patients, positive BoNT-AB titers were found in the MDT. There was a significant correlation between the BoNT/A-AB titers and the anhidrotic area (Spearman's rho = -0.9, P < 0.0001). Both tests provided comparably good results with respect to qualitative antibody detection. In the clinical situation of secondary nonresponse to BoNT/A therapy, the economical NST may be a helpful tool to detect neutralizing BoNT/A-AB.

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Sudomotor testing predicts the presence of neutralizing botulinum A toxin antibodies

Cited by 13 publications

References 28 publications

Botulinum Toxin A reduces neurogenic flare but has almost no effect on pain and hyperalgesia in human skin

Botulinum Toxin A reduces neurogenic flare but has almost no effect on pain and hyperalgesia in human skin

Botulinum Toxin Type B Blocks Sudomotor Function Effectively: A 6 Month Follow Up

Ninhydrin sweat test: A simple method for detecting antibodies neutralizing botulinum toxin type A

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