Table 1.

Risk factors for epilepsy and TSC-related DEE

	Risk factor for epilepsy	Risk factor for co-occurring NDDs	References
TSC2 mutation	X	X	Farach et al.,15,19 Mongrain et al.,16 Ogorek et al.14
Structural abnormalities: tubers and microlesions	X	X	Curatolo et al.,24 Catlett et al.,63 Hulshof et al.,34,100 Pagani et al.101
Myelin pathology		X	Scholl et al.,102 Prohl et al.,103 Peters et al.,104 Sato et al.105
Neural circuit dysfunctions and altered neurotransmission: glutamatergic transmission	X	X	Wu et al.,48 Catlett et al.,63 Cepeda et al.,68 Talos et al.,72 Lozovaya et al.,74 Gataullina et al.,75 Catania et al.76
Neural circuit dysfunctions and altered neurotransmission: GABAergic deficit/imbalance	X	X	Eichmuller et al.,62 Ruffolo et al.,73 Katsarou et al.,78 Amegandjin et al.,106 van Andel et al.107
Non-neural mechanisms: astrocytes	X	X	Zou et al.,83 Sosunov et al.,84 Zimmer et al.27
Non-neural mechanisms: microglia	X	X	Zhang et al.,87,88 Koike-Kumagai et al.,108 Zimmer et al.27
Inflammation, oxidative stress and BBB dysfuntion	X	X	Eichmuller et al.,62 Boer et al.,85 Arena et al.,89 Zimmer et al.,90,95 Mills et al.,91 van Scheppingen et al.,93 Gorter et al.96
ECM remodelling	X	X	Mills et al.,91 Long et al.,97 Bongaarts et al.,98 Broekaart et al.,99 Lewis et al.109
Neurodegeneration progression: tauopathy	–	X	Iyer et al.,110 Kovacs et al.,111 Sarnat et al.,112 Hwang et al.,113 Liu et al.114,115

Most of the cellular, molecular and clinical events play a significant role in determining a high risk for both epilepsy and co-occurring NDDs.