2007 추계 간질학회 보수교육 강의 EEG in Encephalopathy and Coma including Brain Death 이 향운 이화여자대학교 의학전문대학원 신경과 EEG Patterns in Encephalopathy and Coma Diffuse slowing Intermittent delta rhythms EEG patterns usually seen during sleep Alternating pattern Prolonged bursts of delta waves & EEG reactivity Epileptiform activity Triphasic waves Suppression-burst activity Periodic spiking Monorhythmic activity Low-voltage waves Focal abnormalities in coma EEG Changes & Severity of Encephalopathy In mild encephalopathy Slowing of posterior alpha rhythm in mild clouding of consciousness and confusion; alpha to theta range In severe encephalopathy First, high-amplitude irregular delta Lower amplitude below 20 μV, invariant delta activity Suppression-burst pattern Electrocerebral inactivity (ECI) Prognosis from EEG patterns Grave prognosis if invariant low-amplitude delta, suppression-burst, ECI, in the absence of drug intoxication If due to drug intoxication, severely abnormal patterns are quite reversible with high potential for full recovery Diffuse Slowing & Intermittent Delta Diffuse slowing In early phase of coma, gradual dissolution of alpha rhythm interspersed theta frequency, mimicking normal drowsiness Diffuse continuous slowing, theta or delta range Intermittent delta rhythms In initial phase of coma, intermittent rhythmic bilaterally synchronous delta with subcortical, deep frontal, other supratentorial lesions, or metabolic and hypoxic encephalopathy Frontal maximum in adult (FIRDA), or occipital dominance in children (OIRDA) However, TIRDA (temporal) is epileptogenic pattern Frontal Intermittent Rhythmic Delta Activity (FIRDA) Sleep-like EEGs & Alternating Pattern EEG patterns usually seen during sleep Similar to sleep EEG in some types of coma (e.g. sleep spindles or K complexes) with cyclic appearance, influencing sleep-inducing systems Gradual abolition of sleep structures with deepening coma, due to increasing cortical dysfunction or direct brainstem involvement Alternating pattern Cyclic alteration of low-voltage irregular & high-voltage slow waves in coma with Cheyne-Stokes respiration Induce high-voltage slowing with stimulus during lowvoltage period, more aroused during slow-wave period May be due to pacemaker function of arousal system, temporarily released by cortical inhibition, or blood gas changes from respiratory center itself Prolonged Bursts of Delta Waves and EEG Reactivity Prolonged bursts of bilateral high-voltage delta for several seconds or minutes, in various intracranial conditions, mainly with head injuries Delta bursts either spontaneous or secondary to exogenous stimuli, considered as exaggerated K complex, associated with greater muscle activity, restlessness, and attempts to communicate Reactions to stimuli is essential Alerting type (paradoxical activation); increased slow-wave response Blocking type; voltage reduction, or filtering remnants of basic rhythm No response even to repetitive stimulation in deep coma, voltage flattening with or without blocking slow waves, delta wave filtering with nonrhythmical alpha and theta activity, mulscle artifacts without EEG changes Prolonged Delta Bursts by painful stimulation Epileptiform Activity and Periodic Lateralized Epileptiform Discharges (PLEDs) Predominant spikes and/or sharp waves, frequently and not invariably with seizures Generalized paroxysmal activities with myoclonic status epilepticus, or no visible motor phenomena Unilateral continuous spiking can be associated with aphasia or inability to react adequately rather than true unconsciousness Periodic lateralized epileptiform discharges (PLEDs); With coma or without alterations in vigilance (50%) Acute convulsions in vascular structural lesions, or a wide variety of conditions Sometimes with nonconvulsive status epilepticus without effects of IV antiepileptic drugs Periodic Lateralized Epileptiform Discharges (PLEDs) - 1 Periodic Lateralized Epileptiform Discharges (PLEDs) - 2 Suppression-Burst Activity and Periodic Spiking Suppression-burst activity High-voltage bursts of slow waves with intermingled sharp transients or spikes against depressed background or complete flatness Quasi periodically repeated and frequently with diffuse myoclonic jerks Remnants between bursts frequently consist of nonreactive rhythmic activity in alpha and theta ranges Periodic spiking Single or multiple spikes on a flat background activity, closely related to suppression-burst activity, but with higher repetition rate and less prominent or lacking slow waves Periodic spikes accompanied by myoclonic jerks, but no definite one-to-one relation to spikes Burst-Suppression Pattern Suppression-Burst Pattern Monorhythmic Activity Monorhythmic activity in coma patients Normal-looking rhythmical activities in alpha range in deep coma Encountered in unresponsive conditions after brainstem lesions and in severe anoxic encephalopathy Differentiation from normal alpha rhythm Steadily throughout the whole record and diffusely spread or accentuated over anterior regions No reaction to any stimulus “Alpha coma” with unfavorable prognosis In a traditional narrow definition, transient epileptic antemortem stage following burst-suppression pattern Should be differentiated from spindle-like activities, from 10 to 18 cycles/sec rhythms due to intoxication, or normal alpha rhythm in locked-in syndrome Alpha Coma in Anoxic Encephalopathy Alpha Coma in Phenobarbital Intoxication Low-Voltage EEG or Focal Abnormality Low-voltage output EEG Remnants of cerebral activity less than 20 µV, a precursor of electrocerebral silence (ECS) Should not be confused with low-voltage records of conscious subjects Focal abnormalities in coma Associated with focal EEG signs, but blurred or abolished lateralizing signs with deepening coma Localized or unilateral slowing, asymmetrical depression of slow or fast activities, especially of sleep spindles, asymmetric response to exogenous stimuli Depressed prolonged delta bursts over the more affected hemisphere For correct lateralization, differentiation between consistent unilateral accentuated slowing and asymmetrical alerting response is crucial However, localized EEG abnormalities area not uncommon with diffuse encephalopathy, especially nonketotic diabetic coma, apt to produce focal neurological deficits, partial seizures and corresponding EEG signs Anoxic Encephalopathy EEG in anoxic encephalopathy EEG should be obtained at least 5 or 6 hours after cardiopulmonary resuscitation after stabilization To assess the severity of cerebral insult and for prognosis Normal or almost normal EEG after a short episode of cerebral anoxia Unique EEG patterns in anoxic encephalopathy with fatal prognosis Periodic discharges Suppression-burst pattern Alpha coma pattern Electrocerebral inactivity Periodic Discharges and Myoclonic Status Epilepticus in Anoxic Encephalopathy EEG in Metabolic Encephalopathy (I) Hypoglycemia Varying degree of EEG change Profound coma and/or major convulsions with massive spikes Epileptogenic lesions are more likely hypo- than hyperglycemia Even complex partial seizures in insulinoma Hyperglycemia EEG with mixed slow and fast frequency In advanced diabetic coma, pronounced slowing, indistinguishable from hypoglycemic state Focal epileptic seizures are more common in non-ketotic hyperglycemia, but possible in ketotic hyperglycemia EEG in Metabolic Encephalopathy (II) Hepatic encephalopathy Degree of slowing often parallel to ammonia level Posterior alpha rhythm may be preserved during early stage of enhanced slowing, sudden shift and slow substitutes, then massive EEG slowing with or without triphasic waves Triphasic waves are highly indicative of hepatic coma (about 25%), although not specific Replaced by delta slowing and general flattening in profound coma in impending death, often slow delta activity mixed with trains of 14 and 6 Hz positive spikes Renal encephalopathy or Uremia In acute uremia, irregular low-voltage activity with posterior background slowing (theta), and prolonged bursts of bilateral synchronous mixed slow and sharp or spikes with or without widespread myoclonic jerks, grand mals, exceptionally focal seizures; epileptic seizures in 1/3 patients usually due to water-electrolyte imbalance In chronic uremia, usually stable EEG and mental function due to prolonged dialysis, occasional deterioration with seizures and diffuse delta and theta activity, correlated best with BUN fluctuations; generalized spike-wave bursts in 8-9% of uremia, with heightened sensitivity to photic stimulation In children with renal failure, commonly diffuse slowing and generalized bursts of spikes or spike-wave-like activity Triphasic Waves Typical triphasic waves; Medium- to high-voltage triphasic waves in rhythmical trains at 1.5 to 2.5 cycles/sec with sharp transients, bilaterally synchronous and symmetrical over both hemispheres Anterior-posterior time delay as an important criterion but observed with referential or transverse montages Fairly characteristic of hepatic coma, but not specific Continuous triphasic waves considered a type of nonconvulsive status epilepticus in hepatic coma Also in hypoxic states, intoxication, other metabolic or sepsis-associated encephalopathy, subdural hematoma/brainstem infarction, cerebral carcinomatosis, preserved consciousness in Alzheimer’s disease, prion disease, unspecified demented states Confused with sharp and slow waves with absence status of Lennox-Gastaut syndrome Triphasic Waves Lennox-Gastaut Syndrome EEG and Other Etiologies of Coma (I) EEG in supratentorial lesions Always markedly abnormal Focal slowing in lesion site, whereas diffuse slowing parallel to degree of herniation Detailed electroclinical correlation in acute secondary midbrain syndromes EEG in infratentorial lesions Disproportional to neurological signs and EEG abnormalities (e.g. normal looking EEG in apparent comatose behavior) In brainstem infarction with predominant alpha frequency, locked-in syndrome should be differentiated; the only clue is reactive alpha rhythm EEG and Other Etiologies of Coma (II) Infectious diseases Exceptionally prominent diffuse slowing, often rhythmic or quasiperiodic, superimposed theta or alpha area scarce Characteristic EEG patterns Generalized periodic pattern; highly suggestive for SSPE, CJD, or diffuse encephalitis Lateralized periodic complexes; diagnostic importance in herpes simplex encephalitis Epileptic conditions Prolonged coma in convulsive status epilepticus, in postictal states with lingering subclinical paroxysmal activity, in typical and atypical absence status, other types of nonconvulsive status epilepticus Prominent seizure activity, but EEG without spikes does not exclude epileptic nature and complicated by interspersed epileptic seizures in many coma patients Periodic Epileptiform Discharges in Right Temporal Area in Herpes Simplex Encephalitis Subacute Sclerosing Panencephalitis Creutzfeldt-Jakob Disease EEG in Relation to the Depth of Coma Degree and generalization of slowing Related to the level of unresponsiveness Exceptionally prolonged bursts of delta waves secondary to exogenous stimuli In children, degree of slowing is frequently disproportionate to the clinical state Effect of stimulation Good information about coma depth Blocking type of response is replaced by alerting type, and finally unreactive EEG even to repeated stimulation Potentials seen during sleep Progressively scarcer finally disappear with deepening coma Patterns highly suggestive of late midbrain or initial bulbar brain syndrome Progressive voltage depression Extreme slowing with extinction of superimposed fast activities Intermittent isoelectric periods Periodic spiking or burst-suppression activity Monorhythmic unreactive alpha and theta frequency Brain Death (I) Definition and terms for the same clinical entity Aperceptive, areactive, apathic, atonic syndrome Brain death Stage IV coma Coma dépassé Irreversible coma Cerebral death syndrome Irreversible breakdown of cerebral functions For organ transplantation, donorship expanded to anencephalic infants and to non-heart-beating patients Pathophysiology Crucial mechanism is elevation of intracranial pressure, common final pathway, whatever the cause of coma Intensity of pathological changes depends on development of intracranial circulatory arrest Brain Death (II) Neurological signs Absent cortical functions and brainstem activity Fixed pupils with strong light stimulus with exclusion of peripheral third nerve injury Muscle artifacts in EEG have been considered evidence of brainstem functions, but due to hyperexcitability of the nerve membrane caused by artificial hyperventilation Absent spontaneous respiration, no respiration movements after removal from the respirator Apnea testing is necessary to confirm Absent spinal reflexes by Harvard criteria, but simple or complex spinal reflexes after initial phase of spinal shock due to total brain infarction down to C1 level Obscured EEG by very-low-amplitude fast activity due to sustained contraction of scalp muscles should be ruled out by giving a short-acting neuromuscular blocking agent (succinylcholine 20-40 mg IV) EEG in Brain Death (III) Electrocerebral silence (ECS) In adult, single EEG and 6-to 12-hour clinical observation after acute cerebral insult are minimum requirements for brain death Isoelectric EEG to confirm cerebral death Sign of brain death only if neurological signs of cortical and brainstem functions are lacking, intoxication and marked hypothermia should be excluded However, ECS can be found with complete apallic syndrome, with intoxication and full recovery, with hypothermia, with transient decorticate states followed by varying degrees of recovery Brain Death (IV) Technical standards for EEG recording in brain death Minimum of 8 scalp electrodes and reference electrodes to cover major brain areas Interelectrode impedances under 10,000 ohms but over 100 ohms Testing the integrity of the entire recording system Interelectrode distances of at least 10 cm to enlarge the amplitudes and to pick up electrical fields originating in deep structures Sensitivity increase up to 2 µV/mm during most of the recording to distinguish ECS from low-voltage output EEG Use of time constants of 0.3 to 0.4 second Use of monitoring techniques, with simultaneous ECG recording to be mandatory Testing EEG reactivity to exogenous stimuli Recording time of at least 30 minutes Recording to be made only by a qualified technologist Brain Death (V) Recommended guideline by a special task force for confirming brain death in young children Brain death should not be determined until at least 7 days of age Seven days to 2 months: two examinations and two EEGs separated by at least 48 hours Two months to one year: two examinations and two EEGs separated by at least 24 hours Older than one year: similar criteria as an adult, one EEG and at least 12 hours of clinical observation Electrocerebral Silence (ECS) & Double-Distance Montage FP1-T3 F7-T5 T3-O1 FP2-T4 F8-T6 T4-O2 Fz-Pz Cz-Oz Thank you for your attention!