We read with interest the review article by Garg and Sharma [1] on sudden unexplained death in epilepsy (SUDEP) in the pediatric population. We have the following comments.

A pathophysiological mechanism of SUDEP not considered by the authors is Takotsubo syndrome, also known as stunned myocardium or broken heart syndrome. Takotusbo syndrome is an acute onset, usually reversible cardiomyopathy, mainly of the left ventricle, morphologically and functionally characterized by focal or global dyskinesia, hypokinesia, or akinesia of the left ventricular myocardium, resulting in low output failure [2]. Though the outcome is usually fair, it can be fatal in isolated cases, particularly in those with the global type. The syndrome is triggered by physical or emotional stress, associated with a massive dumping of catecholamines (catecholamine storm). It is considered that the sudden overstimulation of adrenergic receptors on the surface of cardiomyocytes results in contractile dysfunction and thus acute heart failure [2]. Epilepsy is the most frequent central nervous system trigger of Takotsubo syndrome [2]. Since it can be complicated by ventricular arrhythmias [2], patients experiencing Takotsubo syndrome may not only die suddenly from acute heart failure but also from asystole or ventricular fibrillation [2].

A second pathophysiological mechanism not considered is neurogenic pulmonary edema (NPE) [3]. NPE is characterized by acutely developing pulmonary edema within minutes or hours following an acute lesion of the central nervous system [3], which usually resolves spontaneously within 24-48 hours after onset [4]. Central nervous system triggers of NPE so far reported include enterovirus 71-associated brainstem encephalitis, subarachnoid bleeding, intracerebral bleeding, traumatic brain injury, stroke, hypoxia, hydrocephalus, or epilepsy, usually with generalized tonic-clonic seizures [3]. NPE may occur after a single seizure or multiple seizures. In a retrospective study of 47 patients, NPE was found on computed tomography scans of the lungs in 19% of the patients experiencing a generalized tonic clonic seizure [5].

Overall, patients with epilepsy, particularly those with poor seizure control, polytherapy with anti-seizure drugs, poor compliance, and multiple comorbidities, should be pros-pectively screened for cardiac and pulmonary disease by electrocardiographic monitoring, echocardiography, stress tests, and pulmonary function tests. Epilepsy patients at risk of cardiac or pulmonary disease should receive primary prophylactic treatment to lower the risk of SUDEP.

1. Garg D, Sharma S. Sudden unexpected death in epilepsy (SUDEP) – What pediatricians need to know. Indian Pediatr. 2020;S097475591600192 [published online ahead of print, 2020 Jun 12].

2. Finsterer J, Wahbi K. CNS disease triggering Takotsubo stress cardiomyopathy. Int J Cardiol. 2014;177:322-29.

3. Finsterer J. Neurological perspectives of neurogenic pulmonary edema. Eur Neurol. 2019;81:94-102.

4. Takagi Y, Imamura T, Endo S, 　Hayashi K, Akiyama S, Ikuta Y. et al. Neurogenic pulmonary edema following febrile status epilepticus in a 22-month-old infant with multiple respiratory virus co-detection: A case report. BMC Infect Dis. 2020;20:388.

5. Mahdavi Y, Surges R, Nikoubashman O, Dague KO, Brokmann JC, Willmes K, et al. Neurogenic pulmonary edema following seizures: A retrospective computed