Table 3.

Summary of commonalities in epileptogenic processes from different acquired acute brain insults.

	Commonalities resulting from acquired acute brain insults	Comments
Partial epilepsies resulting from acquired acute brain insults in adults	Either temporal lobe or neocortical epilepsy Intracranial blood Early post-injury seizures Severity of injury Blood-brain barrier disruption
Partial epilepsies resulting from acquired acute brain insults in children	Early post-injury seizures Intracranial blood Severity of injury Trauma, stroke, autoimmune, neoplastic etiologies	Febrile status and MTS relationship
Post-insult acute EEG alterations (clinical)	Nonconvulsive seizures Periodic discharges Spreading depolarizations	Invasive EEG findings in critically ill patients show that an even higher percentage of patients have nonconvulsive seizures and periodic discharges than can be seen on scalp EEG (regardless of the specific type of acute brain injury).
Genetic aspects (clinical)	Preliminary studies in humans, combined with what has been shown in animal models, implicate genes involved in the inflammatory response and neuronal plasticity.	There have essentially been no comparative studies to date.
Pathologies (clinical)	Common histopathology patterns besides a main structural lesion in epileptic brain tissue encounter astrogliosis and heterotopic neurons in white matter	Difference to non-epileptic lesions with gliosis uncertain; No appropriate animal models for heterotopic neurons
Routes of seizure propagation	Early seizures at site of injury Secondary epileptogenesis engages temporal lobe and thalamocortical networks	Frequency of TLE-like or absence-like phenotypes differ across models; Little network mapping has been performed after TBI, stroke or viral encephalitis
Circuit reorganization	Shift of inhibition from phasic towards tonic. Depolarizing action of GABAergic inhibition, especially during excessive activity Increased glutamatergic drive Increased intrinsic neuronal excitability Canonical rules for seizure generation, independent of species or insult	Differences in specifics, e.g., shifts in GABAA receptor subunit expression differ between etiologies. Many changes are compensatory – trying to stabilize the network. The lack of adequate control tissue from humans makes it difficult to know what electrophysiological signatures are pathological in human tissue
Role of hippocampus and parahippocampal circuits and structural lesions	Variable extent but similar pattern of hippocampal formation pathology (neuron loss in entorhinal cortex Layer III, hippocampus, and dentate gyrus), synaptic reorganization, reactive gliosis
Dysfunctional astrocytes and microglia	Microglial and astroglial activation Dysfunctional K+-buffering Adenosine deficiency	Downregulation of Kir4.1 conductance and block of Cx43- mediated gap junction coupling compromise K+ homeostasis
Inflammatory processes	Generation of an innate immune/inflammatory response Rapid activation of microglia Release of an array of frontline inflammatory molecules from brain resident cells BBB dysfunction associated with inflammatory changes	Type of acute injury determines cellular sources of inflammatory mediators and pathophysiological role of immune mediators; Scarse information on: role in post-stroke, post-TBI or post-encephalitis epileptogenesis acute and subacute neuroinflammatory changes in postmortem human brain potential commonalities across brain injuries
Signaling pathways	Pathway activation after multiple forms of acute brain injury (TBI, SE, stroke) Severity of injury correlates with degree of activation Pathway inhibition modifies outcomes related to spontaneous seizures and learning/memory	Pathway inhibition is antiepileptic in some models and antiepileptogenic in others
Biomarkers	HFOs localize and may be prognostic
Treatment response in patients	Preliminary observations support the hypothesis that drug response is surprisingly similar for different types of acquired epilepsy seen in stroke sequelae, vascular malformation, and tumors diffuse brain damage is more likely to result in pharmacoresistance than other substrates for focal epilepsy	Limitations of the current evidence on drug response in the early days of acquired epilepsy are manifold.
Animal models of acquired epilepsy	Hippocampal pathology
Pharmacology of animal models of acquired epilepsy	Similar pharmacology of evoked kindled seizures and spontaneous recurrent seizures in post-SE models of TLE Occurrence of drug resistant animals in both kindling and post-SE models of TLE	Only few data on the pharmacology of models of TBI, stroke, or viral encephalitis (see text).