Serial systemic immune inflammation indices: markers of acute migraine events or indicators of persistent inflammatory status?

Abstract

Background: Migraine is the most common complex neurological disorder, affecting over a billion people worldwide. Neurogenic inflammation has long been recognized as a key factor in the pathophysiology of migraine though little research has been directed to investigating whether inflammation is greatest in migraine with aura or without, and whether inflammation is a permanent state in migraine or whether is an event related transitory state. Thus, the primary aim of this single-centre, retrospective study was to explore the potential clinical utility of the Serial Systemic Immune-Inflammatory Indices (SSIIi) as a comparative measure of duration and severity of inflammation derived from routine blood cell counts in migraine patients with aura and no-aura both within an acute inpatient setting and as outpatients. Specifically, we assessed the role of two serial white blood cell counts to calculate the SSIIi using the formula: neutrophil count x platelet count/lymphocyte count) between aura and no-aura migraine patients at time of admission to a tertiary care centre in Melbourne, Australia, and following 24 h post admission versus comparable serial measures in 20 out patients with migraine and ongoing symptoms.

Main body: A retrospective analysis was conducted of medical records using baseline demographics and brain imaging findings from 186 migraine hospitalized in-patients who had at least two sets of white blood cell counts drawn within 24 h following their admission to the emergency department of Western Health a tertiary care center in Melbourne, Australia, over an 18-month period. Patients were categorized as having migraine with aura (MA) (N = 67) or without aura (MO) (N = 119) according to ICHD-3 criteria and compared to 2 serial measures in stable in-community acute migraineur controls (N = 20). A mixed-design ANOVA showed a significant main effect of SSIIi between patients with migraine with aura (MA) and migraine without aura (MO) during acute inpatient presentation, in comparison to a convenience sample of outpatients with migraine (MA and MO).

Conclusion: SSIIi levels were significantly lower in patients with migraine with aura (MA), compared to MO. MA showed a greater, though non-significant, decrease between the two measurements compared to those with migraine without aura (MO) and outpatient controls, whose SSIIi levels remained consistently higher. The control group displayed similar findings to MO inpatients, suggesting persistent systemic inflammation in a subset of migraine patients regardless of in patient or outpatient of presentation and highlighting the need for future studies to more rigorously evaluate the role of systemic inflammation in migraine pathophysiology, chronicity, and progression though the multiple phases of migraine including the interictal phase.

Keywords: Aura; Cortical spreading depression; Inflammation; Migraine; Serial systemic Immune-Inflammatory Indices (SSIIi).

Fig. 1

Mean (+/- Standard Error) Serial systemic immune-inflammatory indices (SSIIi) at Time 1 (baseline admission to hospital of in-patients. Refers to first blood test for control migraine outpatients) compared to Time 2 (after 12–24 h) for Migraine without aura (MO), Migraine with aura (MA) and community control migraine outpatients