Factors associated with headache in intravenous immunoglobulin treatment for neurological diseases.

Authors:  Jonas Graf MD, Jens Ingwersen MD, Klaudia Lepka PhD, Philipp Albrecht MD, Hans-Peter Hartung MD PhD FRCP, Marius Ringelstein MD, Orhan Aktas MD

Published: Orcid ID : 0000-0002-4249-4665

Abstract: Objectives: To identify possible risk factors influencing the incidence of intravenous immunoglobulin (IVIg) treatment-related cephalalgia in neurological diseases.

Materials & Methods: Retrospective chart review of neurological patients receiving IVIg treatment between July 13th and August 14th 2017. MS patients receiving natalizumab in the same setting were observed as a reference group.

Results: Patients with headache after IVIg infusion (n=22 infusions) showed a reduced heart rate (by 6.0±8.5 beats per minute (bpm)), but no significant difference in blood pressure. Patients without headache after IVIg infusion (n=69 infusions) showed a higher systolic blood pressure increase and a stronger reduction of the heart rate (by 5.7±8.6 bpm), compared to patients with headache after IVIg infusion. The infusion rate was significantly slower and age significantly lower in patients developing headache after IVIg infusion. Body temperature was unchanged in both groups. Binary logistic regression analysis revealed that blood pressure at baseline and age significantly influence the occurrence of cephalalgia. In reference patients receiving natalizumab (i.e. shorter infusions/smaller infusion volume), systolic blood pressure and heart rate decreased, while body temperature increased. Here, one patient developed headache.

Conclusions: IVIg-associated headache is not associated with an increased blood pressure after infusion, but with a reduced heart rate, a slower infusion rate, female sex and seems to be influenced by baseline systolic blood pressure and age. A reaction to immunoglobulin aggregates, stabilizers or vasoactive mediators are possible explanations. The absence of an association with body temperature does not suggest a systemic immune response as a cause for headache.