Pilot Study Links Possible Lab Markers With Risk of Myasthenic Crisis

A proof-of-concept study in patients with myasthenia gravis (MG) has found that several laboratory markers may signal a higher risk of developing myasthenic crisis (MC).

MC, which commonly occurs within the first few years of MG and in 15% to 20% of patients with the chronic autoimmune disorder, is a result of worsening disease symptoms. Although predicting MG exacerbation and MC through laboratory measures is not currently possible, previous research has shown that factors like certain drugs, inadequate treatment, and sepsis are associated with MC.

Basophils, neutrophils, leukocytes, and platelets are potentially associated with risk of myasthenic crisis | Image Credit: Dee-Sign - stock.adobe.com

Now, findings from the new retrospective pilot study published in Frontiers in Neurology show that levels of basophils, neutrophils, leukocytes, and platelets could be associated with MC risk. These findings, together with real-world data, say the researchers, could help inform risk classification of MC beyond the known risk factors listed above.

“Our study provides initial indications that routine laboratory parameters assessed before the onset of MC could be used as risk predictors for MC occurrence and facilitate early interventions (eg, treatment with immunoglobulins or plasma exchange), possibly preventing MC and mitigating the associated morbidity and mortality,” explained the researchers. “To this end, some studies have investigated the prediction of in-hospital mortality in MC based on selected laboratory parameters. A recent study derived a predictive score for in-hospital mortality of MC using the Myasthenia Gravis Foundation of America (MGFA) score at the onset of the MC, septic shock, and cardiac arrest.”

In their study, the researchers assessed data from 58 patients with MG from a center in Berlin, 15 of whom experienced at least 1 MC. There were 11 patients who experienced 1 MC, 2 patients who experienced 2 MCs, and 2 patients who experienced 3 MCs.

Two regression models—univariable Anderson–Gill and generalized estimating equations (GEE) logistic regression models—deployed by the researchers showed that increased basophil (per 0.01-unit increase: HR, 1.32; 95% C,: 1.02-1.70) and neutrophil (per 1-unit increase: HR, 1.40; 95% CI, 1.14-1.72) counts increased the risk of MC. The models also showed that increases in leukocytes (per 1-unit increase: HR, 1.15; 95% CI, 0.99-1.34) and platelets (per 100-unit increase: HR, 1.54; 95% CI, 0.99-2.38) potentially increased the risk.

MC occurrence did not differ significantly based on antibody status or gender. Elevated C-reactive protein was not associated with risk of MC in either model, although the researchers noted this could be due to the small population included in their study.

“It is interesting that, among others, we identified basophilia as a potential indicator for risk of MC. Classically, basophilia is seen in hypersensitivity reactions of the immediate type (type 1). Basophils are thought to play a role in host defense against parasites. Consequently, associations of basophilia with chronic inflammation and autoimmunity have been described. As such, our data might open novel opportunities to study biomarkers of disease activity in MG.”

The researchers noted that each model accounted for time differently, although both only consider data from before MC occurrence. While the Anderson–Gill model is time dependent and assessed the association between time to MC and the explanatory variables, the GEE logistic model assessed the odds of MC based on the explanatory variables.

Reference

Mehnert A, Bershan S, Kollmus-Heege J, et al. Identifying patients at risk for myasthenic crisis with hemogram and inflammation-related laboratory parameters – a pilot study. Front Neurol. Published online February 25, 2024. doi: 10.3389/fneur.2024.1297997