Management of Status Epilepticus in Adults

Risk factors that have been identified for RSE are encephalitis as a cause, severe consciousness impairment, de novo episodes of SE, delay in initiation of treatment, NCSE, and focal motor seizures at onset [30,32,34,35]. In a more recent study from ICU patients in Switzerland and the US, acute SE etiology (traumatic brain injuries, cerebrovascular accidents, meningoencephalitis, brain tumors, surgical brain lesions, exposure to, or withdrawal from, recreational drugs, prescription drugs, alcohol, metabolic disturbances and fever), coma/stupor, and serum albumin < 35 g/L at SE onset were independent predictors for RSE [36].

Etiology of SE

The 3 most common etiologies for SE are low levels of antiepileptic drugs (AEDs) in 34% of the cases (usually due to noncompliance), remote symptomatic etiologies (history of neurological insults remote to the first unprovoked SE episode, 24%), and cerebrovascular accidents (ischemic and hemorrhagic strokes, 22%). These are followed by hypoxia (13%) and metabolic disturbances (15%). Because 82% of patients in the remote group have a history of cerebrovascular disease, almost 50% have either acute or remote cerebrovascular disease as etiology of SE [19].

In general ICUs, metabolic abnormalities can account for 33% of seizures, drug withdrawal for 33%, drug toxicity for 14.5%, and stroke for 9% to 39% [37,38]. In ICUs, sepsis remains a common etiology of electrographic seizures or periodic epileptiform discharges [39,40], and legal or illegal drugs, such as ciprofloxacin, levofloxacin, piperacillin/tazobactam, cefepime and carbapenems [41–43], lithium or theophylline intoxication, vigabatrin, tiagabine or crack/cocaine, are another [18] (especially when their metabolism is altered due to interactions with other drugs or when their excretion is impaired due to hepatic or renal failure).

Beyond these common causes of SE, a workup for rare etiologies should be entertained. In a systematic review of 513 papers on SE, 181 uncommon causes of SE were identified and subdivided into immunologically mediated disorders, mitochondrial diseases, rare infectious disorders, genetic disorders, and drugs or toxins [18,44].

The most recent knowledge in this category is the contribution of paraneoplastic or autoimmune conditions to a large percentage of previously cryptogenic pharmaco-resistant seizures or super-refractory SE, most in the context of limbic encephalitis. Many of these patients have never experienced seizures or SE before and a new acronym has been devised for them: new-onset refractory status epilepticus (NORSE), ie, a state of persistent seizures with no identifiable etiology in patients without preexisting epilepsy that lasts longer than 24 hour despite optimal therapy [45]. A growing array of autoantibodies against intracellular and surface or synaptic neuronal targets has been described in addition to the previous literature of Rassmussen’s encephalitis and Hashimoto’s encephalopathy [46]. The most common autoantibodies associated with seizures and SE include anti-Hu, anti-Ma2, anti-CV2/CRMP5, anti-Ri, ANNA3, anti-amphiphysin, anti-NMDA receptor, anti-LGI1 and CASPR2, anti-GABA-beta, anti-GluR3, anti-mGluR5 and alpha 3 ganglionic acetylcholine receptor [47,48]. The diagnosis frequently remains elusive due to lack of knowledge or absence of widespread availability of serologic testing (with sometimes weeks-long delay for the results to be available), but the response to treatment with removal of tumor, plasmapheresis, or immunomodulation and immunosuppression is often dramatic.