We read with interest the article by Hocker et al. (2012) reporting on the spectrum of cardiac injury in refractory status epilepticus. According to the data published, markers of cardiac injury seem to be common in patients with refractory status epilepticus (SE), definitely require specific treatment, and (we do hope so) are in a large part reversible. The authors draw the attention to a very important topic in clinical and experimental epileptology. In view of a multimodal treatment schedule in patients with (refractory) seizures, cardiac manifestations pre- and postseizure are considered to be usually benign. To us and as stated by Hocker et al., however, particularly tonic–clonic seizures and SE might lead to overflowing sympathetic activation potentially resulting in myocyte damage and consecutive cardiac contractile dysfunction or susceptibility to arrhythmias (Zijlmans et al., 2002; Schneider et al., 2010; Eskandarian et al., 2011; Stollberger et al., 2011). Furthermore, the neuro-cardio-endocrine axis has attracted attention, since acute neurologic insults (including seizures) have been reported to be associated with the so-called takotsubo cardiomyopathy (TC) several years ago (Schneider et al., 2010; Stollberger et al., 2011). TC is clinically characterized by chest pain and dyspnea paralleled by elevation of cardiac enzyme levels and transient wall-motion abnormality. Because TC has been reported after isolated convulsive seizures, partial nonconvulsive, as well as generalized convulsive SE and is potentially linked to sudden unexpected death in epilepsy (SUDEP) (Stollberger et al., 2011), this highlights exceeding catecholamine release as an important aspect of epilepsy. As a consequence we want to point to the new and important standard of cardiac evaluation to differentiate between cardiac or noncardiac events in the emergency room as well as to determine the extent of dysfunction (usually ventricular) in a contemporary manner: the measurement of the n-terminal pro-brain natriuretic peptide (NT-proBNP) or brain-type natriuretic peptide (BNP). Especially after acute myocardial infarction, the determination of BNP or NT-proBNP is generally considered to be useful in detecting left-ventricular dysfunction (McMurray et al., 1998) and has been shown to be related to poor outcome (Wang et al., 2004). High NT-proBNP concentrations are associated with cardiovascular events (myocardial infarction, coronary heart disease, unstable angina, heart failure, congenital heart defects, stroke, and transient ischemic attack) in adults and children and provide prognostic information on mortality (Kistorp et al., 2005). Systemically, BNP supports the reduction of blood pressure, peripheral vascular resistance, and sympathetic tone by dumping baroreceptors, diminishing catecholamine release, and suppressing sympathetic outflow from the central nervous system (Yang et al., 1992). In addition, natriuretic peptides seem to be associated with the intensity of brain tissue ischemia, reflecting increased biosynthesis and secretion especially from the hypothalamus (Franzoni et al., 1992; Sviri et al., 2003). In a study of our workgroup, we observed increased postictal NT-proBNP levels in children with tonic–clonic seizures and febrile convulsions compared to children with partial motor seizures, syncope, or controls (Rauchenzauner et al., 2007). Furthermore, plasma concentrations of NT-proBNP were significantly higher 4 h compared to 24–48 h postictal. This clearly points to an increase in stress and noradrenaline release during epileptic seizures, backed up by increasing blood pressure and heart rate and/or electrocardiography changes around the time or even before onset. Finally, data concerning heart damaging by recurrent seizures as well as the association of cardiac ischemia during seizures and SUDEP risk is far from conclusive to date (Tigaran et al., 2003; P-Codrea Tigaran et al., 2005). To us, there is an urgent need for comprehensive studies focusing on cardiac function and homeostasis/integrity to acquire robust data in order to prevent cardiac damage and SUDEP in adults and children with epilepsy.
To the Editors:
The authors declare no conflicts of interest. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.