SE is divided into 4 phases (Table 8.5). Prodromal phase may include confusion, myoclonus, and increasing seizure frequency without intervening loss of consciousness. Stage 1 is divided into incipient (continued seizure of >5 min duration) and early (5–30 min duration).

EEG staging includes (i) discrete seizures with interictal slowing; (ii) waxing/waning of ictal discharges; (iii) continuous ictal discharge evolving into continuous ictal discharges interspersed by flat EEG; and (iv) Post-ictal: PLEDs/PEDs with flat background [5].

SE evolves from an isolated seizure when there is a failure of seizure containment leading to the transformation of isolated seizure(s) to SE. Initially (ms/s), there is increased glutamate release and ion channel activation receptor phosphorylation and desensitization. After approximately 30–45 min, there is receptor trafficking with GABA_A-R (β2-3, ɤ subunits) internalized from synapse to cytosol where they are endocytosed and destroyed, leading to reduced number of GABA_A receptors at the synaptic membrane, with simultaneous recruitment from cytosol to the membrane of glutamatergic AMPA/NMDA receptors (NR1 subunits). As a result of this trafficking, the number of functional NMDA receptors per synapse increases while the number of functional GABAA receptors decreases [6]. This contributes to the resistance of prolonged SE to GABAergic medication such as benzodiazepines.

Pathophysiology of epilepsia partialis continua is poorly understood. It may involve cortical reflex myoclonus which originates from hypersynchronous discharges of neuronal aggregates in the cortex and may involve long-loop reflexes via the ventrolateral posterior nucleus of the thalamus to generate cortical myoclonus [7].

During the initial acute stage of SE, there is an increase in blood pressure, increase in cerebral blood flow and oxygen utilization, increased serum lactate, and, initially, increased glucose levels. There may be associated respiratory and metabolic acidosis. Subsequently, blood pressure normalizes and may fall, respiration becomes depressed, with falling oxygen and rising CO₂ levels, decrease in cerebral blood flow and brain oxygenation, and decrease in glucose level. There may be hyperthermia. These factors result in energy mismatch, with higher brain energy utilization than supply and exacerbation of neuronal injury. During later stages of both convulsive SE and in NCSE, there is an increase in serum levels of neuron-specific enolase, a marker of brain injury. Neuronal injury may occur even in the absence of metabolic derangement, and without hypoxemia, hypotension, hypoglycemia, and hyperthermia.