We thank the reader for their interest in our article [1], and for addressing additional putative pathophysiological mechanisms that may contribute to Sudden unexpected death in epilepsy (SUDEP). The authors suggest a potential role of Takotsubo syndrome. Although it has been well recognised that seizures may trigger this syndrome in adults, the role of this entity in SUDEP in general continues to be debated and in pediatric SUDEP, is definitely uncertain. In a review including 74 patients who developed Takotsubo syndrome in association with a seizure, the age range was 18-82 years [2]. Of these, a fatal outcome occurred in only two (3%) patients. This is similar to mortality reported in the International Takotsubo registry [3]. Considering the rarity of fatality, in association with the aforementioned age range, Takotsubo syndrome seems an unlikely contributor to SUDEP pathogenesis in children. Autopsy studies in SUDEP patients indicate that cardiac pathology comprises interstitial fibrosis, myocyte hyper-trophy as well as vascular wall thickening [4]. However, whether these are the effects of multifactorial influences such as anti-seizure medications or even epilepsy itself, or the cause of SUDEP remains unclear. Moreover, none of these features are pathognomonic of "active catecholamine myocarditis" pathology observed in TTS [5].

The authors also suggest a role of neurogenic pulmonary edema (NPE) in the pathogenesis of SUDEP. NPE has been consistently noted in patients with epilepsy and serves almost as a pathological biomarker for SUDEP. However, the reported degree of pulmonary edema has only been to a mild extent, as observed on autopsies in the MORTEMUS study [6]. 　Additionally, NPE following a seizure tends to be short-lived. Hence, both ante-mortem and post-mortem evidence suggest that NPE following seizures is a common but mild finding, making the link between SUDEP and NPE as a causative factor tenuous.

We agree with the authors’ suggestion that underlying cardiac and pulmonary diseases in persons with epilepsy, particularly among those who are refractory to medical therapy, should be treated. However, whether this strategy generates a reduction in SUDEP occurrence necessitates more prospec-tively collected data, particularly among children and adolescents.

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

2. Finsterer J, Bersano A. Seizure-triggered Takotsubo syndrome rarely causes SUDEP. Seizure. 2015;31:84-7.

3. Templin C, Ghadri JR, Diekmann J, Napp LC, Bataiosu DR, Jaguszewski M, et al. Clinical features and outcomes of Takotsubo (Stress) cardiomyopathy. NEJM. 2015;373:929-38.

4. Nascimento FA, Tseng ZH, Palmiere C, Maleszewski JJ, Shiomi T, McCrillis A, et al. Pulmonary and cardiac pathology in sudden unexpected death in epilepsy (SUDEP). Epilepsy Behav. 2017;73:119-25.

5. Mitchell A, Marquis F. Can Takotsubo cardiomyopathy be diagnosed by autopsy? Report of a presumed case presenting as cardiac rupture. BMC Clin Pathol. 2017;17:4.

6. Ryvlin P, Nashef L, Lhatoo SD, Bateman LM, Bird J, Bleasel A, et al. Incidence and mechanisms of cardiorespiratory arrests in epilepsy monitoring units (MORTEMUS): A retrospective study. Lancet Neurol. 2013;12:966-77.