R Sutter PW Kaplan European Journal of Neurology 2014 Uncovering clinical and radiological associations of triphasic waves in acute encephalopathy: a case-control study R Sutter PW Kaplan European Journal of Neurology 2014

Distinct, repetitive elements 3 phases http://eegatlas-online.com/index.php/en/alphabetical-index/triphasics-guest TRIPHASIC WAVES Distinct, repetitive elements 3 phases Negative wave Surface positive high amplitude sharp transient >70 µV Decrease on stimulation Central > frontal localization ? Lack of unilaterality More V shaped (gentler rate of decline on the second phase) More background activity No response to benzodiazepines

Background 8-20% rate of non convulsive status epilepticus in critically ill encephalopathic patients Many reported EEG patterns of unclear significance in critically ill encephalopathic patients Triphasic waves have been reported in case reports and series in patients with hepatic encephalopathy and other toxic/metabolic encephalopathies Reader variance in classifying triphasics Debate on their etiology, epileptic classification and prognostic significance Reported 30-100% mortality in patients with triphasic waves This paper published in 2014 “with an aim to confirm and quantify assumed clinical and neuroradiological associations with triphasic waves and to elucidate whether poor outcome is independently related to triphasic waves” Generalized spike waves are more acute, narrowed angled, briefer frontopolar empahasis Triphasics are longer duration, frontocentral, stimulus altered, blunter

Data collected over 8 years (2004-2012) Setting: ICU patients METHODS: Data collected over 8 years (2004-2012) Setting: ICU patients Diagnosis: Encephalopathy Definition: altered consciousness with change in cognition or with an acute perceptual disturbance that was not better accounted for by pre-existing dementia Cases: with Triphasic waves (TWs) Controls: without TWs Chart review EEGs: at least 2 separate EEG with at least 20minutes of data EEG readers: blinded to clinical diagnosis CT or MRI: read by 2 neuroradiologist, 1 neurologist blinded to clinical diagnosis Outcomes: Primary: death Encephalopathy: developed hours to days Seizures: convulsions <5minutes, convulsive SE >5minutes, or repetitive convulsions without return to baseline Non-consulsive seizures and status EEG readers: if divergent – consensus reached after joint review Imaging: WMC (mild, mod, severe), atrophy (cortical, subcortical) , infarction, ICH, brain tumros

Mortality: Cases 19% Controls 11% OR 2 CI 0.85-4.67% Older p 0.06 Inter-rater agreement: Kappa: measures inter-rater agreement for qualitative categorical items, (mutually exclusive categories) between TWO raters Takes into account the possibility of agreement occurring by chance Complete agreement k = 1 , no agreement other than that expected by change k ~ 0 EEG k = 0.81 Neuro imaging k = 0.76

ALL significant an ODDs ratio that those disease were RF to be associated with TWs The conditions that had significant ODDS ratios where further evaluated with MV regression, in which they still showed significant ODDs ratio PREDICTOR Multi variable evaluated if other predictors are effecting the univariable odds ratio (verse indirect effect from another predictor) Conditional univariable logistic regression – used to calculate ODDs ratio IF significant in univariable logistic regression – included in conditional multivariable regression Stepwise logistic regression using step forward and step backward selection And Akaike information To assess collinerarity multiple linear regression Mean variable inflation factor was 1.11 – ruling out high collinearity of the included variables MEANS -----

Cumulative Effect of Independent Predictors 1 independent predictor – OR TW 2.4 2 or mote OR 9.2

Strengths Provided more data to support an association between toxic metabolic encephalopathies (infection, liver disease) and presence of triphasic waves on EEG Accounted for cofounding factors of background EEG activity and GCS

Limitations No causation with case control study Not all patients had continuous cEEG Non differential mis classification: under estimate hypothesized relationship Differential mis classification over estimate

https://www.ncbi.nlm.nih.gov/pubmed/23684126 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5340556/ O'Rourke D, Chen PM, Gaspard N, Foreman B, McClain L, Karakis I, Mahulikar A, Westover MB . Response Rates to Anticonvulsant Trials in Patients with Triphasic-Wave EEG Patterns of Uncertain Significance. Neurocrit Care 2016;24:233–239. Bermeo-Ovalle A .Triphasic Waves: Swinging the Pendulum Back in this Diagnostic Dilemma Epilepsy Curr. 2017 Jan-Feb;17(1):40-42. doi: 10.5698/1535-7511-17.1.40. Kaplan PW, Sutter R. Affair With Triphasic Waves-Their Striking Presence, Mysterious Significance, and Cryptic Origins: What are They?. J Clin Neurophysiol. 2015 Oct