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Does Electroencephalography Provide a “Windowto the Brain” for the Neurologically Ill?

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D iagnosing seizures in acutely ill neu-rologically impaired patients admittedto the hospital is complex. Electro-

encephalography (EEG) is the best method foridentifying seizures and their surrogate bio-marker, ie, epileptiform discharges (EDs). Assuch, EEG serves as a complement to the neu-rologic examination, “a window to the brain” ifyou will.

In this issue of Mayo Clinic Proceedings,Betjemann et al1 report on a retrospective 5-yeartertiary care cohort study of the diagnostic yieldof continuous EEG (cEEG) in patients in a gen-eral hospital setting who were being evaluatedfor spells and altered mental status. For thepurpose of this investigation, cEEG designatesprolonged EEG monitoring in a single patientlasting 1 to 2 days, although in some patientsthe monitoring was terminated earlier when theEEG correlates of a clinical “spell” werecaptured.

Seizures, EDs, and nonepileptiform ab-normalities were the study end points in 1048nonetracheally intubated, spontaneously ven-tilating patients with a mean EEG observationperiod of 7.5 hours. Overall, 79% of the cEEGfindings were reported to be abnormal, withdiffuse slowing noted as the primary abnor-mality in 706 patients (67%). Focal slowingwas identified in another 358 patients (34%).EDs were recorded in 194 patients (18.5%)including periodic discharges in 41 (3.9%).Evidence of seizures on cEEG appeared in 78patients (7.4%), although more than 90% ofthese did not appear as discrete events. Of thosewho eventually had cEEG evidence of seizures,64.8% had the seizures identified within thefirst hour of cEEG, and 97% had the seizuresdiscovered within the first day.

In a separate subanalysis, patients with andwithout seizures were compared, and there wereno major differences distinguishing the groups.However, in the subset of patients with a knownbrain mass, multivariate logistic regressionanalysis determined that the presence of spellspredicted seizures on cEEG (P�.001), whereasalteration in mental status did not. Intracerebralhemorrhage, subarachnoid hemorrhage, and

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traumatic brain injury are reported in the liter-ature to be forms of acute brain injury that areassociated with an increased risk of seizures.2-4

Although the research by Betjemann et al didnot have sufficient numbers of patients tomeaningfully comment on these subgroups ofpatients, they did note that “stroke” tended to beassociated with the nonseizure group in themultivariate analysis (P¼.21).1

If seizures (for any reason) were recordedin the assessment of spells and altered mentalstatus in the research by Betjemann et al, therewas a lower likelihood of the patient beingdischarged from the hospital (odds ratio, 0.45;95% CI, 0.27-0.76). Furthermore, patientswho had seizures on the cEEG had a tendencyfor greater mortality (P¼.06).

Why Should We Worry About Seizuresin the Acutely Ill Patient?Nonconvulsive seizures (NCSs) and status epi-lepticus (SE), along with nonconvulsive SE(NCSE), are associated with acute structural andmetabolic brain insults in hospitalized patients,including patients admitted to the neurologicintensive care unit (ICU).2-4 These diagnosesalso correlate with mental status impairmentand the evaluation of that impairment.5 Delay inthe diagnosis of patients with SE correlates witha reduced response to treatment, and the pres-ence of NCSE increases the risk of permanentbrain damage and death.2 Recurrent clinicalseizures have waning motor features over time,and recognizing NCSs or NCSE is possible onlywith EEG, making its use critical for diagnosis.6

Discovering NCSs or NCSE is a prerequisite fortreatment, and more than half of the patientswith NCSE improve after they receive anti-epileptic drugs.2 Seizures and EDs are reportedto be prevalent in patients admitted to specialcare units of the hospital (eg, emergency de-partments, ICUs, and epilepsy monitoringunits).2-6 The report by Betjemann et al nowexpands the utility of cEEG to the general hos-pital population to detect NCSs and othernonepileptiform abnormalities.

Electroencephalographic monitoring isavailable in most hospital settings. The major

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EDITORIAL

cortical generators for EEG waveforms are thepyramidal cells in layers 3 and 5 of the neo-cortex. Although these cells are quite sensitiveto the cellular effects of hypoxia, ischemia, andchanges in the metabolic milieu, individualEEG recordings lack specificity in determiningthe exact nature of the underlying brain path-ogenesis. In the hospital, serial EEGs are capa-ble of providing dynamic information aboutcerebral function and trends over time. Themeans to acquire outpatient EEG monitoringmay be limited by resource availability andcost. Routine EEG represents a brief sample ofthe electrocerebral activity at a specific pointin time. Previous reports comparing routineEEG with cEEG have shown that routine EEGis not adequate for optimal seizure identifi-cation.3 As such, cEEG is often more infor-mative than a 20-minute recording if seizuresor spells are suspected. Consistent with mostcEEG studies,3,4 Betjemann et al1 found thatNCSs and NCSE, when present, were con-firmed in most patients within the first 24hours of recording.

Why Should We Pursue cEEG in theHospital?The findings of Betjemann et al demonstrate theutility of using cEEG to assess patients in thegeneral hospital setting (only 25% were ina neurologic ICU) who experiencemental statuschanges and spells. The observation of seizuresand EDs in this group of nonintubated hospitalpatients is unique. Although the study resultsreflect the “first-interpreter” assessment of theEEG reports, excellent interrater reliability(k¼0.88) has been shown by this group be-tween the actual EEG tracings and an assessmentof the EEG reports previously for seizures in theICU and currently for the general hospital set-ting (k>0.95).1

There are limitations of note in the study byBetjemann et al. The retrospective design restrictsfurther assessment of the electroclinical spectrumof EEG and clinical features. Selecting groups ofpatients at greater risk for seizures hampers anaccurate interpretation of prevalence. SeveralEEGs had EDs, including 13.4%with EDs on theEEGbut without recorded seizures during cEEG.The EDs have a high specificity for patients withseizures, yet they may also occur as an epi-phenomenon in acute brain dysfunction andinjury and, therefore, do not serve as an absolute

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marker for seizures but rather as a “potential”marker (as the authors correctly point out). Inaddition, even generalized period discharges onthe EEG may not imply a poor patient outcomecompared with patients who have EEG evidenceof NCSs or NCSE.6,7 Furthermore, EEG inter-pretation is a subjective and learned skill. Differ-ences in interpretation of periodic patterns andNCSE may exist even in experienced handsand between centers.8,9 Multicenter agreementregarding these waveforms relative to outcome isgreatly needed.

Of the primary outcome measures in thestudy by Betjemann et al, electrographic sei-zures were identified in 7.4% of patients.However, their use of cEEG recordings fromnonconsecutive patients introduces bias byvirtue of the greater clinical suspicion for patientswith spells (and for those with acute changes inmental status) in whome NCSs and NCSE arealways at the top of the differential diagnosis.Seizures and SE were lumped into broad groupsin the study, and, therefore, precise quantificationand characterization of this groupof patientswith“seizures” is limited in their cohort study. Incontrast to other studies,10 mental status alter-ations in the study by Betjemann et al were lessassociated with seizures compared with an EEGindication of spells. The results of this studycannot be directly compared with those of otherreports with a wide range of seizures noted inpatients with mental status changes (includingcoma).3-6 Nevertheless, the importance of thearticle by Betjemann et al lies in offering out-come measures using EEG in the general hos-pital setting. This type of information will affectcare from neurologists and neurohospitalists byhelping them design evidence-based monitor-ing and treatment protocols.

With increasing outcome benefit demon-strated for “sick” patients in the hospital, whywould clinicians not pursue cEEG? If EDs andseizures are absent within the first few hours ofrecording, the likelihood of capturing seizureswith additional recording becomes progres-sively less likely (as Betjemann et al suggest),and little benefit is shown beyond 1 day ofrecording. The precise value of cEEG-facilitateddiagnosis (eg, seizure detection coupled withtreatment), and the resulting improvements inpatient outcomes, indeed suggests that cEEGcan provide a valuable “window to the brain”for neurologically ill patients.11

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William O. Tatum, DODepartment of Neurology

Mayo ClinicJacksonville, FL

Joseph I. Sirven, MDDepartment of Neurology

Mayo ClinicScottsdale, AZ

Correspondence: Address toWilliamO.Tatum,DO,Depart-ment of Neurology, Mayo Clinic, Cannaday Bldg, 2E, 4500 SanPablo Rd, Jacksonville, FL 32224 (tatum.william@mayo.edu).

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Josephson SA.Diagnostic yield of electroencephalography in a gen-eral inpatient population. Mayo Clin Proc. 2013;88(4):326-331.

2. Jordan KG, Schneider AL. Emergency (“stat”) EEG in the era ofnonconvulsive status epilepticus. Am J ElectroneurodiagnosticTechnol. 2009;49(1):94-104.

3. Pandian JD, Cascino GD, So EL, Manno E, Fulgham JR. Digitalvideo-electroencephalographic monitoring in the neurological-

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neurosurgical intensive care unit: clinical features and outcome.Arch Neurol. 2004;61(7):1090-1094.

4. Claassen J, Mayer SA, Kowalski RG, Emerson RG, Hirsch LJ.Detection of electrographic seizures with continuous EEGmonitoring in critically ill patients. Neurology. 2004;62(10):1743-1748.

5. Privitera M, Hoffman M, Moore JL, Jester D. EEG detection ofnontonic-clonic status epilepticus in patients with altered con-sciousness. Epilepsy Res. 1994;18(2):155-166.

6. Husain AM, Horn GJ, Jacobson MP. Non-convulsive statusepilepticus: usefulness of clinical features in selecting patientsfor urgent EEG. J Neurol Neurosurg Psychiatry. 2003;74(2):189-191.

7. Jette N, Moseley BD. Generalized periodic discharges: morelight shed on the old “GPEDs.” Neurology. 2012;79(19):1940-1941.

8. Benbadis SR, Tatum WO. Prevalence of nonconvulsive statusepilepticus in the comatose patient. Neurology. 2000;55(9):1421-1423.

9. Tatum WO. How not to read an EEG: introductory state-ments. Neurology. 2013;80(1, suppl 1):S1-S3.

10. Towne AR, Waterhouse EJ, Boggs JG. Prevalence of noncon-vulsive status epilepticus in comatose patients. Neurology.2000;54(2):340-345.

11. Crepeau A, Rabinstein AA, Fugate JE, et al. Continuous EEG intherapeutic hypothermia after cardiac arrest: prognostic andclinical value. Neurology. 2013;80(4):339-344.

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