Abstract
OBJECTIVE—To compare a recently developed immunoprecipitation assay (IPA) to the mouse protection bioassay (MPB), currently considered the "gold standard", for detecting antibodies against botulinum toxin A (BTX-A) and to correlate these assay results with clinical responses to BTX-A injections. METHODS—MPB and IPA assays were performed on serum samples from 83 patients (38 non-responders, 45 responders) who received BTX-A injections. Six non-responders had serum tested on two separate occasions. Some patients also received a "test" injection into either the right eyebrow (n=29) or right frontalis (n=19). RESULTS—All patients antibody positive (Ab+) by MPB were also Ab+ by IPA, whereas an additional 19 patients (17 with reduced or no clinical response) who were MPB Ab− were Ab+, with low titres, by IPA. Two of these 19 patients (non-responders) were initially MPB Ab− but later became MPB Ab+. Similar to previous studies, the sensitivity for the MPB was low; 50% for clinical, 38% for eyebrow, and 30% for frontalis responses whereas the IPA sensitivity was much higher at 84% for clinical (p<0.001), 77% for eyebrow (p=0.111, NS) and 90% for frontalis responses (p<0.02). The IPA specificity was 89% for clinical, 81% for eyebrow, and 89% for frontalis responses, whereas the MPB specificity was 100% for all three response types, which were all non-significant differences. CONCLUSIONS—Both assays had high specificity although the sensitivity of the IPA was higher than the MPB. In addition, the IPA seems to display positivity earlier than the MPB, and as such, it may prognosticate future non-responsiveness. Eyebrow and frontalis "test" injections correlated well with clinical and immunological results and are useful in the assessment of BTX non-responders.
Full Text
The Full Text of this article is available as a PDF (122.9 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Berardelli A., Formica A., Mercuri B., Abbruzzese G., Agnoli A., Agostino R., Caraceni T., Carella F., De Fazio G., De Grandis D. Botulinum toxin treatment in patients with focal dystonia and hemifacial spasm. A multicenter study of the Italian Movement Disorder Group. Ital J Neurol Sci. 1993 Jun;14(5):361–367. doi: 10.1007/BF02340723. [DOI] [PubMed] [Google Scholar]
- Clarke C. E. Therapeutic potential of botulinum toxin in neurological disorders. Q J Med. 1992 Mar;82(299):197–205. [PubMed] [Google Scholar]
- Davidson B. J., Ludlow C. L. Long-term effects of botulinum toxin injections in spasmodic dysphonia. Ann Otol Rhinol Laryngol. 1996 Jan;105(1):33–42. doi: 10.1177/000348949610500106. [DOI] [PubMed] [Google Scholar]
- Eleopra R., Tugnoli V., Rossetto O., Montecucco C., De Grandis D. Botulinum neurotoxin serotype C: a novel effective botulinum toxin therapy in human. Neurosci Lett. 1997 Mar 14;224(2):91–94. doi: 10.1016/s0304-3940(97)13448-6. [DOI] [PubMed] [Google Scholar]
- Geller B. D., Hallett M., Ravits J. Botulinum toxin therapy in hemifacial spasm: clinical and electrophysiologic studies. Muscle Nerve. 1989 Sep;12(9):716–722. doi: 10.1002/mus.880120904. [DOI] [PubMed] [Google Scholar]
- Hanna P. A., Jankovic J. Mouse bioassay versus Western blot assay for botulinum toxin antibodies: correlation with clinical response. Neurology. 1998 Jun;50(6):1624–1629. doi: 10.1212/wnl.50.6.1624. [DOI] [PubMed] [Google Scholar]
- Houser M. K., Sheean G. L., Lees A. J. Further studies using higher doses of botulinum toxin type F for torticollis resistant to botulinum toxin type A. J Neurol Neurosurg Psychiatry. 1998 May;64(5):577–580. doi: 10.1136/jnnp.64.5.577. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jankovic J., Brin M. F. Therapeutic uses of botulinum toxin. N Engl J Med. 1991 Apr 25;324(17):1186–1194. doi: 10.1056/NEJM199104253241707. [DOI] [PubMed] [Google Scholar]
- Jankovic J., Schwartz K., Donovan D. T. Botulinum toxin treatment of cranial-cervical dystonia, spasmodic dysphonia, other focal dystonias and hemifacial spasm. J Neurol Neurosurg Psychiatry. 1990 Aug;53(8):633–639. doi: 10.1136/jnnp.53.8.633. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jankovic J., Schwartz K. Response and immunoresistance to botulinum toxin injections. Neurology. 1995 Sep;45(9):1743–1746. doi: 10.1212/wnl.45.9.1743. [DOI] [PubMed] [Google Scholar]
- Lew M. F., Adornato B. T., Duane D. D., Dykstra D. D., Factor S. A., Massey J. M., Brin M. F., Jankovic J., Rodnitzky R. L., Singer C. Botulinum toxin type B: a double-blind, placebo-controlled, safety and efficacy study in cervical dystonia. Neurology. 1997 Sep;49(3):701–707. doi: 10.1212/wnl.49.3.701. [DOI] [PubMed] [Google Scholar]
- Notermans S., Dufrenne J., Schothorst M. Enzyme-linked immunosorbent assay for detection of Clostridium botulinum toxin type A. Jpn J Med Sci Biol. 1978 Feb;31(1):81–85. doi: 10.7883/yoken1952.31.81. [DOI] [PubMed] [Google Scholar]
- Palace J., Nairne A., Hyman N., Doherty T. V., Vincent A. A radioimmuno-precipitation assay for antibodies to botulinum A. Neurology. 1998 May;50(5):1463–1466. doi: 10.1212/wnl.50.5.1463. [DOI] [PubMed] [Google Scholar]
- Shone C., Wilton-Smith P., Appleton N., Hambleton P., Modi N., Gatley S., Melling J. Monoclonal antibody-based immunoassay for type A Clostridium botulinum toxin is comparable to the mouse bioassay. Appl Environ Microbiol. 1985 Jul;50(1):63–67. doi: 10.1128/aem.50.1.63-67.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Siatkowski R. M., Tyutyunikov A., Biglan A. W., Scalise D., Genovese C., Raikow R. B., Kennerdell J. S., Feuer W. J. Serum antibody production to botulinum A toxin. Ophthalmology. 1993 Dec;100(12):1861–1866. doi: 10.1016/s0161-6420(93)31384-9. [DOI] [PubMed] [Google Scholar]
- Zuber M., Sebald M., Bathien N., de Recondo J., Rondot P. Botulinum antibodies in dystonic patients treated with type A botulinum toxin: frequency and significance. Neurology. 1993 Sep;43(9):1715–1718. doi: 10.1212/wnl.43.9.1715. [DOI] [PubMed] [Google Scholar]