B(I)RD Watching: A Way to Stratify Seizure Risk?

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1 B(I)RD Watching: A Way to Stratify Seizure Risk? Current Literature In Clinical Science Brief Potentially Ictal Rhythmic Discharges in Critically Ill Adults. Yoo JY, Rampal N, Petroff OA, Hirsch LJ, Gaspard N. JAMA Neurol 2014;71: IMPORTANCE: Brief potentially ictal rhythmic discharges, termed B(I)RDs, have been described mainly in neonates, and their significance in adults remains unclear. OBJECTIVE: To describe the incidence of B(I)RDs in critically ill patients and investigate their association with seizures and outcome. DESIGN, SETTING, AND PARTICIPANTS: We reviewed the records of prospectively identified patients with B(I)RDs and patients serving as controls matched for age (±5 years) and primary diagnosis. MAIN OUTCOMES AND MEASURES: The prevalence of seizures during continuous electroencephalography and functional outcome, as measured by the Glasgow Outcome Scale, were determined. RESULTS: We identified B(I)RDs in 20 patients (2%). The pattern most often consisted of very brief (1 3 seconds) runs of sharply contoured theta activity without obvious evolution. All patients with B(I)RDs had cerebral injury, and in cases with a single focal lesion (11 [55%]), B(I)RDs were localized in the same region in all but 2 cases (18%). Patients with B(I)RDs were more likely to have seizures during continuous electroencephalography than were patients without B(I)RDs (15 of 20 [75%] vs 10 of 40 [25%]; P <.001), and 9 patients with B(I)RDs (60%) had only subclinical seizures. Brief potentially ictal rhythmic discharges were identified before seizures in all but 1 case (93%) and ceased in all 12 cases (80%) in which seizures were controlled. Patients with B(I)RDs tended to have a worse outcome than controls (16 [80%] vs 25 [63%]); however, this finding was not statistically significant. CONCLUSIONS AND RELEVANCE: Brief potentially ictal rhythmic discharges in critically ill patients are associated with a high prevalence (75%) of electrographic seizures and might serve as an early predictor of seizures during subsequent monitoring. A larger prospective study is needed to better understand their clinical and prognostic significance. Commentary Seizures are deceptively difficult to define. Clinical seizures with an EEG correlate are rarely problematic, but seizures can be purely clinical, with no scalp EEG correlate, or conversely, purely electrographic, with no apparent clinical correlate. The latter is a common occurrence in neurologically critical patients. There is recognition that seizure definitions set somewhat arbitrary cut points in a continuum that spans interictal and ictal findings. In reality, the determination of whether a given pattern is ictal is more a probabilistic one than a binary choice of ictal or interictal (1). Yet there are still sound reasons for establishing definitions of electrographic seizures. A common language is needed for clinical and research purposes. Definition of an EEG pattern as ictal often, but not always, signals changes in or intensification of treatment. Most attempts to define EEG criteria for seizures incorporate several features of the EEG (4). There is usually a requirement that the activity is rhythmic or periodic. Frequency is important, with frequencies of 3 4 Hz or greater usually representing ictal patterns, with the understanding that lower Epilepsy Currents, Vol. 14, No. 6 (November/December) 2014 pp American Epilepsy Society frequency discharges are also potentially ictal. Evolution, or change over time, is characteristic of most seizures, and evolution in frequency, spatial characteristics, or morphology is a part of most definitions. Duration of the EEG pattern is often included but admittedly an arbitrary criterion. While it may not make biological sense to set a lower bound for the length of a seizure, there are practical issues in distinguishing brief rhythmic runs from more fully elaborated seizures, and a lower limit of 10 seconds duration is often used. It is the sub-10-second realm that Yoo and coworkers explore in their article. In doing so, they coin a new term: B(I)RDs. The acronym stands for brief, potentially ictal rhythmic discharges, with the parenthetical (I) indicating that the discharges are potentially, but not definitely ictal. They defined B(I)RDs as very brief (<10 second) lateralized runs of rhythmic activity with a frequency greater than 4 Hz. For these brief discharges, features of evolution were not required. Similar patterns have been previously described in neonates. The authors set out with several goals: to report the prevalence, the significance, and the prognostic implications of these brief rhythmic discharges in adults. To do so, Yoo and colleagues queried a large database of continuous EEG recordings at a single institution. The median age of subjects was 65 (range 13-88). Of the 1,135 studies recorded over a span of 18 months, 19 were reported and confirmed to contain B(I)RDs. An additional 101 studies that 341

2 B(I)RD Watching were not reported to contain B(I)RDs were re-reviewed for the sole purpose of identifying any previously unidentified B(I)RDs. Only one additional example was found, resulting in a total of 20 studies containing B(I)RDs. The remaining 100 studies that did not contain B(I)RDs (60 random and 40 matched) served as controls. Descriptive features of the identified B(I)RDs included the frequency (theta discharges were most common seen in 70%), duration (typical was 1 3 seconds), and morphology (most were sharp, few were sinusoidal, and none showed clear evolution). Nearly all were unifocal (19/20), and they were not clearly state dependent. The B(I)RDs were very frequent in 30% (at least every minute), moderately frequent in 60% (at least every hour ), and more rare in 10% (less than 1/hour). Nearly all patients with B(I)RDs (19/20) had an acute or subacute brain injury, with strokes and high-grade or metastatic brain tumors most common, and all had abnormal imaging. When there was a single imaging focus, the B(I)RDs co-localized to that focus in the vast majority of cases (82%). Next, the researchers examined correlations with clinical features. In patients with B(I)RDs, there was a much stronger association with independent, unequivocal electrographic seizures (75%) than in controls (25%; p < 0.001). In addition to this statistical association, the EEG morphology and location of the B(I)RDs and seizures were usually similar, and in all of the 80% of patients who achieved seizure control with AED therapy, the B(I)RDs also ceased. In patients with B(I)RDs and seizures, the B(I)RDs preceded the appearance of the first unequivocal seizure in almost every instance. Periodic lateralized epileptiform discharges (PLEDs) were also observed in many of these patients, but they had a different relationship to the B(I)RDs. PLEDs were not statistically more frequent in patients with B(I)RDs than controls. In contrast to the behavior of B(I)RDs, most PLEDs persisted after achieving seizure control with AEDs. Both PLEDs and B(I)RDs were independently associated with an increased risk of seizures, but only PLEDs were statistically associated with worse outcome in this relatively small sample. It has been 10 years since the initial report of another previously underreported pattern in neurologically critically ill patients: stimulus-induced rhythmic, periodic, or ictal discharges, or SIRPIDs (2). These stimulus induced discharges are now very familiar to and encountered in the daily work of most EEG readers who interpret studies in the neurosciences ICU. Both the initial report of SIRPIDs and the present report of B(I)RDs examined the EEG finding of interest in a population of neurologically critically ill patients and compared them to a contemporary group without the finding. Like the patients with B(I)RDs, those with SIRPIDs had also frequently suffered an acute brain injury, and many also had unequivocal seizures. However, there are probably more differences than similarities. B(I)RDs do not appear to be state dependent, while SIRPIDs, by definition, are stimulus and arousal dependent. SIRPIDs may be an order of magnitude more common than B(I)RDs. The relationship between B(I)RDs and seizures with respect to morphology, location, and response to AED therapy appears much closer than that between SIRPIDs and seizures. The pathophysiology of SIRPIDs has been hypothesized to involve an abnormality in arousal mechanisms, akin to other abnormal and normal arousal related patterns. One study in which SPECT was performed in a patient with SIRPIDs also supported a non-ictal significance of this pattern (3). What conclusions can be drawn from this early report of B(I)RDs? First, if we look for them in a critically ill population, we will see them; however, they appear to be much less common than SIRPIDs. Given the close relationship with seizures, as well as the specific temporal relationship with seizures (B(I)RDs were almost always seen before unequivocal seizures), the identification of B(I)RDs should put the EEG reader on notice. At a minimum, strong consideration should be given to extending the EEG recording to monitor for seizures. Initiation of AED therapy based on B(I)RDs alone could be considered. Are B(I)RDs simply brief seizures? Should we rethink the 10-second minimum criterion for seizures? These questions need to be addressed with further work. In the meantime, EEG readers should be B(I)RDs watching. by David Spencer, MD References 1. Osorio I, Lyubushin A, Sornette D. Toward a probabilistic definition of seizures. Epilepsy Behav 2011;22(suppl 1):S Hirsch LJ, Claassen J, Mayer SA, Emerson RG. Stimulus-induced rhythmic, periodic, or ictal discharges (SIRPIDs): A common EEG phenomenon in the critically ill. Epilepsia 2004;45: Zeiler SR, Turtzo LC, Kaplan PW. SPECT-negative SIRPIDs argues against treatment as seizures. J Clin Neurophysiol 2011;28: 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 2013;30(1):

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4 American Epilepsy Society Epilepsy Currents Journal Disclosure of Potential Conflicts of Interest Section #1 Identifying Information 1. Today s Date: 01/02/13 2. First Name David Last Name Spencer Degree MD 3. Are you the Main Assigned Author? Yes No If no, enter your name as co-author: 4. Manuscript/Article Title: B(I)RD watching: a way to stratify seizure risk? 5. Journal Issue you are submitting for: 14-6 Section #2 The Work Under Consideration for Publication Did you or your institution at any time receive payment or services from a third party for any aspect of the submitted work (including but not limited to grants, data monitoring board, study design, manuscript preparation, statistical analysis, etc.)? Complete each row by checking No or providing the requested information. If you have more than one relationship just add rows to this table. Type No Money Paid to You Money to Your Institution* Name of Entity Comments** 1. Grant $ Consulting fee or honorarium 3. Support for travel to meetings for the study or other purposes 4. Fees for participating in review activities such as data monitoring boards, statistical analysis, end point committees, and the like 5. Payment for writing or reviewing the manuscript 6. Provision of writing assistance, medicines, equipment, or administrative support. 7. Other * This means money that your institution received for your efforts on this study. ** Use this section to provide any needed explanation. Page 2 11/26/2014

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