Postictal serotonin levels are associated with peri-ictal apnea

Abstract

Objective: To determine the relationship between serum serotonin (5-HT) levels, ictal central apnea (ICA), and postconvulsive central apnea (PCCA) in epileptic seizures.

Methods: We prospectively evaluated video EEG, plethysmography, capillary oxygen saturation (SpO₂), and ECG for 49 patients (49 seizures) enrolled in a multicenter study of sudden unexpected death in epilepsy (SUDEP). Postictal and interictal venous blood samples were collected after a clinical seizure for measurement of serum 5-HT levels. Seizures were classified according to the International League Against Epilepsy 2017 seizure classification. We analyzed seizures with and without ICA (n = 49) and generalized convulsive seizures (GCS) with and without PCCA (n = 27).

Results: Postictal serum 5-HT levels were increased over interictal levels for seizures without ICA (p = 0.01), compared to seizures with ICA (p = 0.21). In patients with GCS without PCCA, serum 5-HT levels were increased postictally compared to interictal levels (p < 0.001), but not in patients with seizures with PCCA (p = 0.22). Postictal minus interictal 5-HT levels also differed between the 2 groups with and without PCCA (p = 0.03). Increased heart rate was accompanied by increased serum 5-HT levels (postictal minus interictal) after seizures without PCCA (p = 0.03) compared to those with PCCA (p = 0.42).

Conclusions: The data suggest that significant seizure-related increases in serum 5-HT levels are associated with a lower incidence of seizure-related breathing dysfunction, and may reflect physiologic changes that confer a protective effect against deleterious phenomena leading to SUDEP. These results need to be confirmed with a larger sample size study.

Figure 1. Serum 5-HT levels and ictal central apnea (ICA) after generalized convulsive and focal seizures

The mean serum interictal 5-HT levels are shown in light green bars and postictal 5-HT levels (ng/mL) are shown in dark green bars for the 2 groups; the left 2 columns without ICA (n = 32) and the right 2 columns with ICA (n = 17). The levels of postictal serum 5-HT in the absence of ICA was higher when compared to interictal levels (p = 0.01). However, in the presence of ICA, no significance was observed (p = 0.21).

Figure 2. Serum 5-HT levels and postconvulsive central apnea (PCCA) after generalized convulsive seizures

(A) Elevated levels of postictal 5-HT in generalized convulsive seizures (GCS). The mean serum interictal 5-HT levels are shown in light green bars and postictal 5-HT levels (ng/mL) are shown in dark green bars for the 2 seizure groups: PCCA (n = 8) and non-PCCA (n = 19). The levels of postictal serum 5-HT in the absence of PCCA were higher when compared to interictal levels (p < 0.001), but not when PCCA occurred (p = 0.22). (B) Elevated serum 5-HT levels in the absence of PCCA. The change in 5-HT (postictal minus interictal) was plotted for seizures without PCCA (in gray) and with PCCA (in red). The change in serum 5-HT (postictal minus interictal levels) was moderate when the 2 groups were compared (p = 0.03).

Figure 3. Association of heart rate (HR) with serum 5-HT

(A) The differences in serum 5-HT levels (postictal minus interictal) were plotted against the change in HR (difference in HR at clinical onset of seizure minus baseline) for seizures without postconvulsive central apnea (PCCA) (n = 19) shown as blue dots. Increased change in serum 5-HT was associated with an increase in heart rate (p = 0.03). (B) Similar analysis revealed no association between serum 5-HT levels and heart rate for patients with PCCA (n = 8) and shown as red dots (p = 0.42).