Botulinum toxin antibody titres: measurement, interpretation, and practical recommendations

J Neurol. 2023 Mar;270(3):1524-1530. doi: 10.1007/s00415-022-11424-0. Epub 2022 Nov 24.

Abstract

Botulinum toxin (BT) therapy may be blocked by antibodies (BT-AB) resulting in BT-AB induced therapy failure (ABF). BT-AB may be detected by the mouse lethality assay (MLA), the mouse diaphragm assay (MDA) and the sternocleidomastoid test (SCMT). For the first time, we wanted to compare all three BT-AB tests and correlate them to subjective complaint of complete or partial secondary therapy failure in 37 patients with cervical dystonia (25 females, 12 males, age 51.2 ± 11.4 years, disease duration 12.4 ± 6.3 years). Complaint of therapy failure was not correlated with any of the BT-AB tests. MDA and MLA are closely correlated, indicating that the MDA might replace the MLA as the current gold standard for BT-AB measurement. The SCMT is closely correlated with MDA and MLA confirming that BT-AB titres and BT's paretic effect are in a functional balance: low BT-AB titres are reducing BT's paretic effect only marginally, whereas high BT-AB titres may completely block it. When therapy failure is classified as secondary and permanent, BT-AB evaluation is recommended and any BT-AB test may be applied. For MDA > 10 mU/ml, MLA > 3 and SCMT < 25%, ABF is highly likely. MDA < 0.6 mU/ml are therapeutically irrelevant. They are neither correlated with pathologic MLA nor with pathologic SCMT. They should not be the basis for treatment decisions, such as switching dystonia therapy to deep brain stimulation. All other results are intermediate results. Their interactions with therapy efficacy is unpredictable. In these cases, BT-AB tests should be repeated or one or two additional test methods should be applied.

Keywords: Antibodies; Botulinum toxin; Mouse diaphragm assay; Mouse lethality assay; Sternocleidomastoid test; Therapy; Therapy failure; Titres.

MeSH terms

  • Animals
  • Antibodies
  • Botulinum Toxins, Type A*
  • Dystonic Disorders*
  • Female
  • Male
  • Mice
  • Torticollis* / drug therapy
  • Treatment Failure

Substances

  • Botulinum Toxins, Type A
  • Antibodies