Abstract
Background
Generalized triphasic waves (TPWs) occur in both metabolic encephalopathies and non-convulsive status epilepticus (NCSE). Empiric trials of benzodiazepines (BZDs) or non-sedating AED (NSAEDs) are commonly used to differentiate the two, but the utility of such trials is debated. The goal of this study was to assess response rates of such trials and investigate whether metabolic profile differences affect the likelihood of a response.
Methods
Three institutions within the Critical Care EEG Monitoring Research Consortium retrospectively identified patients with unexplained encephalopathy and TPWs who had undergone a trial of BZD and/or NSAEDs to differentiate between ictal and non-ictal patterns. We assessed responder rates and compared metabolic profiles of responders and non-responders. Response was defined as resolution of the EEG pattern and either unequivocal improvement in encephalopathy or appearance of previously absent normal EEG patterns, and further categorized as immediate (within <2 h of trial initiation) or delayed (>2 h from trial initiation).
Results
We identified 64 patients with TPWs who had an empiric trial of BZD and/or NSAED. Most patients (71.9 %) were admitted with metabolic derangements and/or infection. Positive clinical responses occurred in 10/53 (18.9 %) treated with BZDs. Responses to NSAEDs occurred in 19/45 (42.2 %), being immediate in 6.7 %, delayed but definite in 20.0 %, and delayed but equivocal in 15.6 %. Overall, 22/64 (34.4 %) showed a definite response to either BZDs or NSAEDs, and 7/64 (10.9 %) showed a possible response. Metabolic differences of responders versus non-responders were statistically insignificant, except that the 48-h low value of albumin in the BZD responder group was lower than in the non-responder group.
Conclusions
Similar metabolic profiles in patients with encephalopathy and TPWs between responders and non-responders to anticonvulsants suggest that predicting responders a priori is difficult. The high responder rate suggests that empiric trials of anticonvulsants indeed provide useful clinical information. The more than twofold higher response rate to NSAEDs suggests that this strategy may be preferable to BZDs. Further prospective investigation is warranted.
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References
Bahamon-Dussan JE, Celesia GG, Grigg-Damberger MM. Prognostic significance of EEG triphasic waves in patients with altered state of consciousness. J Clin Neurophysiol Off Publ Am Electroencephalogr Soc. 1989;6:313–9.
Eidelman LA, Putterman D, Putterman C, Sprung CL. The spectrum of septic encephalopathy. Definitions, etiologies, and mortalities. JAMA. 1996;275:470–3.
Ely EW, Shintani A, Truman B, Speroff T, Gordon SM, Harrell FE, et al. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA. 2004;291:1753–62.
Bickford RG, Butt HR. Hepatic coma: the electroencephalographic pattern. J Clin Invest. 1955;34:790–9.
Ogunyemi A. Triphasic waves during post-ictal stupor. Can J Neurol Sci. 1996;23:208–12.
Primavera A, Traverso F. Triphasic waves in Alzheimer’s disease. Acta Neurol Belg. 1990;90:274–81.
Niimi Y, Hiratsuka H, Tomita H, Inaba Y, Moriiwa M, Kato M, et al. A case of metrizamide encephalopathy with triphasic waves on EEG. Nō Shinkei Brain Nerve. 1984;36:1167–72.
Martínez-Rodríguez JE, Barriga FJ, Santamaria J, Iranzo A, Pareja JA, Revilla M, et al. Nonconvulsive status epilepticus associated with cephalosporins in patients with renal failure. Am J Med. 2001;111:115–9.
Kaplan PW, Birbeck G. Lithium-induced confusional states: nonconvulsive status epilepticus or triphasic encephalopathy? Epilepsia. 2006;47:2071–4.
Hormes JT, Benarroch EE, Rodriguez M, Klass DW. Periodic sharp waves in baclofen-induced encephalopathy. Arch Neurol. 1988;45:814–5.
Wieser HG, Schindler K, Zumsteg D. EEG in Creutzfeldt–Jakob disease. Clin Neurophysiol Off J Int Fed Clin Neurophysiol. 2006;117:935–51.
Aguglia U, Gambardella A, Oliveri RL, Lavano A, Camerlingo R, Quattrone A. Triphasic waves and cerebral tumors. Eur Neurol. 1990;30:1–5.
Hirsch LJ, LaRoche SM, Gaspard N, Gerard E, Svoronos A, Herman ST, et al. American Clinical Neurophysiology Society’s Standardized Critical Care EEG Terminology: 2012 version. J Clin Neurophysiol Off Publ Am Electroencephalogr Soc. 2013;30:1–27.
Kaya D, Bingol CA. Significance of atypical triphasic waves for diagnosing nonconvulsive status epilepticus. Epilepsy Behav EB. 2007;11:567–77.
Boulanger J-M, Deacon C, Lécuyer D, Gosselin S, Reiher J. Triphasic waves versus nonconvulsive status epilepticus: EEG distinction. Can J Neurol Sci J Can Sci Neurol. 2006;33:175–80.
Fountain NB, Waldman WA. Effects of benzodiazepines on triphasic waves: implications for nonconvulsive status epilepticus. J Clin Neurophysiol Off Publ Am Electroencephalogr Soc. 2001;18:345–52.
Jirsch J, Hirsch LJ. Nonconvulsive seizures: developing a rational approach to the diagnosis and management in the critically ill population. Clin Neurophysiol Off J Int Fed Clin Neurophysiol. 2007;118:1660–70.
Chong DJ, Hirsch LJ. Which EEG patterns warrant treatment in the critically ill? Reviewing the evidence for treatment of periodic epileptiform discharges and related patterns. J. Clin Neurophysiol Off Publ Am Electroencephalogr Soc. 2005;22:79–91.
Sutter R, Kaplan PW. Electroencephalographic criteria for nonconvulsive status epilepticus: synopsis and comprehensive survey: EEG criteria for NCSE. Epilepsia. 2012;53:1–51.
Claassen J, How I. Treat patients with EEG patterns on the ictal-interictal continuum in the neuro ICU. Neurocrit Care. 2009;11:437–44.
Litt B, Wityk RJ, Hertz SH, Mullen PD, Weiss H, Ryan DD, et al. Nonconvulsive status epilepticus in the critically ill elderly. Epilepsia. 1998;39:1194–202.
Sutter R, Stevens RD, Kaplan PW. Significance of triphasic waves in patients with acute encephalopathy: a nine-year cohort study. Clin Neurophysiol Off J Int Fed Clin Neurophysiol. 2013;124(10):1952–8.
Holtkamp M, Meierkord H. Nonconvulsive status epilepticus: a diagnostic and therapeutic challenge in the intensive care setting. Ther Adv Neurol Disord. 2011;4:169–81.
Fagan KJ, Lee SI. Prolonged confusion following convulsions due to generalized nonconvulsive status epilepticus. Neurology. 1990;40:1689–94.
Kaplan PW. Nonconvulsive status epilepticus in the emergency room. Epilepsia. 1996;37:643–50.
Drislane FW. Presentation, evaluation, and treatment of nonconvulsive status epilepticus. Epilepsy Behav EB. 2000;1:301–14.
Disclosures
DOR, PMC, AM, LM, and BF report no relevant disclosures. NG received research support from the Belgian Fund for Scientific Research. MBW received research support from the National Institute of Health (NIH-NINDS, 1K23NS090900-01), the Phyllis & Jerome Lyle Rappaport Foundation, and the Andrew David Heitman Neuroendovascular Research Fund.
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Deirdre O’Rourke and Patrick M. Chen contributed equally to this study.
On behalf of the Critical Care EEG Monitoring Research Consortium (CCEMRC).
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O’Rourke, D., Chen, P.M., Gaspard, N. et al. Response Rates to Anticonvulsant Trials in Patients with Triphasic-Wave EEG Patterns of Uncertain Significance. Neurocrit Care 24, 233–239 (2016). https://doi.org/10.1007/s12028-015-0151-8
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DOI: https://doi.org/10.1007/s12028-015-0151-8