Generalized periodic discharges in the critically ill: a case-control study of 200 patients

Abstract

Objective: Generalized periodic discharges are increasingly recognized on continuous EEG monitoring, but their relationship to seizures and prognosis remains unclear.

Methods: All adults with generalized periodic discharges from 1996 to 2006 were matched 1:1 to controls by age, etiology, and level of consciousness. Overall, 200 patients with generalized periodic discharges were matched to 200 controls.

Results: Mean age was 66 years (range 18-96); 56% were comatose. Presenting illnesses included acute brain injury (44%), acute systemic illness (38%), cardiac arrest (15%), and epilepsy (3%). A total of 46% of patients with generalized periodic discharges had a seizure during their hospital stay (almost half were focal), vs 34% of controls (p = 0.014). Convulsive seizures were seen in a third of both groups. A total of 27% of patients with generalized periodic discharges had nonconvulsive seizures, vs 8% of controls (p < 0.001); 22% of patients with generalized periodic discharges had nonconvulsive status epilepticus, vs 7% of controls (p < 0.001). In both groups, approximately half died or were in a vegetative state, one-third had severe disability, and one-fifth had moderate to no disability. Excluding cardiac arrest patients, generalized periodic discharges were associated with increased mortality on univariate analysis (36.8% vs 26.9%; p = 0.049). Multivariate predictors of worse outcome were cardiac arrest, coma, nonconvulsive status epilepticus, and sepsis, but not generalized periodic discharges.

Conclusion: Generalized periodic discharges were strongly associated with nonconvulsive seizures and nonconvulsive status epilepticus. While nonconvulsive status epilepticus was independently associated with worse outcome, generalized periodic discharges were not after matching for age, etiology, and level of consciousness.

Figure 1. Generalized periodic discharges with a focal seizure

A woman in her 40s, 3 days after liver transplantation complicated by sepsis and renal failure. She was comatose. (A) Her initial continuous EEG monitoring demonstrated frequent generalized periodic discharges, occasionally with triphasic morphology. (B–D) Three consecutive pages of EEG about 2 hours later, when she developed focal status epilepticus with right hemisphere onset, maximal in the right frontal parasagittal region (box in B) that evolved before ending abruptly (halfway through panel D). There was no clinical correlate on video.

Figure 2. Generalized periodic discharges (GPDs) and seizures

(A) Comparison of seizure occurrence at any time in patients with GPDs vs controls (%). (B) Comparison of seizures during continuous EEG monitoring (cEEG) in patients with GPDs vs controls (%). (C) Timing of first recorded seizure in patients with GPDs vs controls (patients with first seizure/total patients consecutively monitored on cEEG). CSE = convulsive status epilepticus; CSz = convulsive seizure; NCSE = nonconvulsive status epilepticus; NCSz = nonconvulsive seizure; Sz = seizure.

Figure 3. Functional outcome at hospital discharge (%)

(A) All patients (n = 200 in each group). (B) Excluding cardiac arrest (n = 171 in each group). (C) Cardiac arrest only (n = 29 in each group). *p = 0.049. GPD = generalized periodic discharge; MCS = minimally conscious state; PVS = persistent vegetative state.