Hiding in plain sight? A review of post-convulsive leukocyte elevations

Abstract

During physiological stress responses such as vigorous exercise, emotional states of fear and rage, and asphyxia, the nervous system induces a massive release of systemic catecholamines that prepares the body for survival by increasing cardiac output and redirecting blood flow from non-essential organs into the cardiopulmonary circulation. A curious byproduct of this vital response is a sudden, transient, and redistributive leukocytosis provoked mostly by the resultant shear forces exerted by rapid blood flow on marginated leukocytes. Generalized convulsive seizures, too, result in catecholamine surges accompanied by similar leukocytoses, the magnitude of which appears to be rooted in semiological factors such as convulsive duration and intensity. This manuscript reviews the history, kinetics, physiology, and clinical significance of post-convulsive leukocyte elevations and discusses their clinical utility, including a proposed role in the scientific investigation of sudden unexpected death in epilepsy (SUDEP).

Keywords: SUDEP; catecholamine; leukocyte demargination; leukocyte margination; leukocytosis; neurogenic pulmonary edema; oxygen conserving reflex; seizure.

Figure 1

Schematic hypothetical representation of pulmonary demargination during two different seizures. The circular red and blue structures shown represent the collective of all pulmonary alveolar capillaries. The blue and red halves represent the arterial and venous sides, respectively, while the white center represents alveoli. (A) Normal, non-seizure state characterized by an equilibrium between margination and demargination and by a normal marginated leukocyte pool. (B) During GTCSs exhibiting mostly preserved ventilation only minor increases in blood flow through pulmonary alveolar capillaries occur, resulting in minimal leukocyte demargination and minor increases in the peripheral leucocyte count. (C) By contrast, GTCSs exhibiting severe respiratory compromise or apnea drive major increases in blood flow through the pulmonary capillaries, causing major leukocyte demargination and major increases in the peripheral leukocyte count. The arrows above each figure represent the direction of pulmonary blood flow, from arterial to venous. The larger size of the arrows in (B,C) represents increased blood flow through the alveolar capillaries during a seizure. GTCS, generalized tonic clonic seizure.