False Laterahation by Surface EEG of Seizure Onset in Patients with Temporal Lobe Epilepsy and Gross Focal Cerebral Lesions Michele Sammaritano, MD, FRCP(C), Alain de Lotbinisre, MD, Frederick Andermann, MD, FRCP(C), Andre Olivier, MD, PhD, FRCS(C), Pierre Gloor, MD, PhD, and Luis F. Quesney, MD, PhD Medically intractable temporal lobe seizures developed in 3 patients with radiological and clinical evidence of a gross focal cerebral lesion acquired early in life. All had bilateral independent epileptogenic discharges from the lateral and inferomesial regions of both hemispheres. Scalp and sphenoidal electroencephalographic (EEG) recordings suggested that the seizures originated from the side contralateral to the known cerebral lesion. Because the lateralizing evidence presented by the ictal EEG conflicted with the clinical data, depth electrodes were implanted stereotaxically to determine the side of onset of the seizures. These studies showed that the seizures originated from the limbic structures of the damaged hemisphere in all 3 patients. At operation the mesial temporal lobe structures showed gliotic changes in all. The patients have remained seizure-free for 3 to 13 years postoperatively. These findings suggest that depth electrode recordings may be required to clarify the lateralization of seizure onset in such cases. Extracranial EEG findings must be interpreted with caution in epileptic patients who have gross focal lesions. Sammaritano M, de Lotbinibre A, Andermann F, Olivier A, Gloor P, Quesney L F False lateralization by surface EEG of seizure onset in patients with temporal lobe epilepsy and gross focal cerebral lesions. Ann Neurol 21:361-367, 1787 We studied 3 patients with complex partial seizures of suspected temporal lobe onset and with clinical and radiological evidence of a gross lateralized focal cerebral lesion. All had medically intractable epilepsy, and previous investigations had failed to adequately localize the onset of the clinical seizure discharge. Scalp and sphenoidal electroencephalographic (EEG) recordings showed a bitemporal, interictal, independent epileptic discharge, predominating on the side of the lesion in 2 patients and contralaterally in 1. In all 3, the ictal discharge recorded during spontaneous clinical seizures appeared to originate from the more normal side, i.e., contralateral to the cerebral lesion. In recordings from stereotaxically implanted depth electrodes, however, the EEG onset of spontaneous clinical seizures was clearly localized to the limbic structures of the damaged hemisphere. Case Reports Patient 1 A 25-year-old left-handed woman had had a normal birth and normal developmental milestones. At age 7 months, she had suffered a febrile illness that was accompanied by con- vulsions, described as meningoencephalitis after inoculation with diphtheria-pertussis-tetanus vaccine, which left her with a tight hemiparesis. At age 11 years, she started to have two types of complex partial seizures. In the first type, she had an aura described as a scary feeling, as if someone were going to grab het from behind, and she would remain motionless. She then stared and appeared frightened, her face would become flushed, she would groan, become unresponsive, and then show automatic behavior. At times she would turn her head to the left or have chewing movements. In the second type, following her aura of fear, she would flex both legs at the knee, turn her head and body to the left, and make pedalling movements with her legs. Neurological examination showed a mild right facial weakness and a mild right infantile hemiparesis with hemiatrophy and athetotic posturing of the right hand. Her full-scale I Q was 71; verbal IQ, 70; and performance IQ, 70. Skull roentgenograms showed thickening of the left cranial vault and the computed tomographic (CT) scan showed an enlarged left lateral ventricle, suggestive of a primary atrophic process in the left hemisphere (Fig 1A). Bilateral sodium amytal testing via the internal carotid arteries showed that most of her speech function was represented in the right cerebral hemisphere. In this patient, a right craniotomy had been performed elsewhere 8 months previously on the side of maximal epileptic discharge, oppo- From the Department of Neurology and Neurosurgery, McGill University, Montreal Neurological Institute, 3801 University St, Montreal, Qdbec, H3A, 2B4, Canada. Received Mar 12, 1986, and in revised form Aug 4. Accepted for publication Aug 4, 1986. Address correspondence to Dr Andermann. 36 1 B A C 362 Annals of Neurology Vol 2 1 No 4 April 1987 - Fig 1. (A) Computed tomographic (CT)scan of Patient 1, showing an enkzrged ldt lateral ventricle. (B) Pneumoencephalogram of Patient 2, showing atrophy in ldt hemisphere. (C) C T scan of Patient 3, showing an enlarged lt$ lateral ventricle with three small areas of hypodensity in the le$t posterior limb of the internalcapsule. (L = left; R = right.) site the atrophic side. No cortical excision was carried out on the basis of the electrocorticogram, which showed maximal epileptic discharge located posteriorly in her dominant right temporal lobe. Scalp and sphenoidal EEG recordings were performed after the anticonvulsant medication was reduced. Figure 2 shows interictal epileptiform activity that involved both inferomesial temporal regions, with left-sided predominance. Phase reversals were recorded primarily at the left sphenoidal electrode (SPl), and less frequently at the right (SP;!) and in the right midtemporal region (T4). Figure 3 shows an extracranial EEG record of one of this patient’s typical complex partial seizures. Three of these were recorded, and in all, the ictal EEG discharge first began to appear in the right temporal region. At its onset it involved both the inferomesial and midlateral aspect of the right temporal lobe in the form of rhythmic sharp-wave activity (see a m in Figure 3). Two seconds later, it spread to the contralateral hemisphere, but the amplitude predominance was right-sided, particularly in the right temporal lobe region, with phase reversals at SP2 and T4. During one EEG recording, the patient experienced the clinical onset of a complex partial seizure at least 10 seconds before a definite electrographic discharge was seen in the E B G however, some flattening of the EEG was seen at the beginning of the clinical symptoms. Although this could not be clearly lateralized, it suggested that there was ictal activity in an area incapable of producing C.M. 83-2785 Fig 3 . Prstierat I . Extracrunial electroenqbbabgraphic recording taken with scalp and spbenoidzl electrodes, showing a typicul c o m p h partial seizure. See text for descrigzon. (Symbolsfor electmrode positions us in Figure 2.) Sammaritano et aI: False Laceralization by Surface FEG 363 Seizure Onset LA 1-4- Fig 4. Patient 1 . Depth electrode electroencephalographicrecording of a complex partial seizure, obtained Sy telemetry. See text far description. The depth electrodes were inserted horizontally and contacts of each strand labeled as follows: LA and RA = kfi and right anterior temporal strands, with deepest contacts aimed at the amygdala; LB and RB = lt$t and right intermediate temporal strands with akepest contacts aimd at the anterior hippocampus; LFC and RFC = I& and right anterior frontal strands with the deepest contacts aimed at the anterior cingukzle gyrus; and LFS and RFS = Itfit and right superior frontalstrands with the deepest contacts aimed at the mesial aspect of the supplementary motor region. The deepest contdcts in each strand are numbered 1, with each higher number placed more laterally and superficially. The distance between neighboring contacts equals 5 mm. The most superficial contacts are recordedfmm the lateral suvface convexity. a signal that could be identified as a seizure discharge in the surface EEG. Because of the apparent discrepancy between the clinical and radiological evidence for a left-sided lesion and the rightsided onset of the EEG seizure discharge, depth electrodes were inserted stereotaxically into both temporal and frontal lobes, according to a technique previously described E3, 77. Figure 4 shows a typical complex partial seizure recorded with depth electrodes. The seizure onset (see awow in Figure 4) started in the left temporal lobe as an attenuation of background activity recorded from the amygdaloid (LA 1-4) and hippocampal (LB 1-4) regions, with subsequent rhythmic 364 Annals of Neurology C M 83-3397 t m . Vol 21 No 4 April 1987 sharp and slow wave activity and desynchronization in these areas. This electrographic onset corresponded to the patient's typical warning of fear, and during this warning, the seizure discharge remained confined to the left amygdala and left hippocampus. Thirty-six seconds after seizure onset, the ictal discharge spread to the right temporal lobe. Initially it involved maximally the amygdaloid region and anterior temporal neocortex, with attenuation of background activity at RA 1-4 and RA 4-7, followed by high-frequency rhythmic activity. It then spread to the right hippocampal region and both frontal lobes. The high-amplitude, rhythmic polyspike activity in the temporal structures, particularly in the neocortex, was of higher voltage on the right than on the left. All nine clinical complex pmial seizures recorded with depth electrodes had onset in the left temporal lobe. Using both extracranial and intracranial electrodes, a bitemporal background disturbance was recorded, with a left-sided, or damaged hemisphere, predominance. Electrical stimulation through the depth electrodes showed that the left amygdala exhibited the lowest threshold (1.5 mA) for induction of the patient's typical warning associated with an afterdischarge. A left anterior temporal lobectomy, including the amygdala and anterior hippocampus, was carried out. Marked atrophy of the left temporal lobe was found, with pronounced induration along the first temporal gyms, temporal pole, and amygdaloid region. The preexcision electrocorticogram showed numerous interictal spike and sharp wave discharges from the left temporal cortex, which were of low amplitude, however. Background activity Fig 5 . Patient 2. Extracranial electroencephalographicrecording of a complex partial seizure obtained with scalp and sphenoidzl electrodes. See text far description. (Fpl = ldt fmntopolar; Fp2 = right frontopolar; 01 = lejit occipital; 0 2 = right occipital; other abbreviations as in Figure 2.) over the left temporal lobe was markedly depressed. Following excision of the anterior temporal cortex and amygdala, residual epileptiform activity was recorded from the insular and parahippocampal gyri. Histological examination showed diffuse gliosis and focal neuronal loss of the cortex and white matter. The patient has remained seizure-free for 4 years following her operation. Patient 2 A 2 1-year-old left-handed man suffered perinatal cerebral anoxia secondary to a traumatic forceps delivery which left him with a right hemiparesis. Generalized seizures developed in infancy. At age 10, complex partial seizures developed. H e denied any warning of his attacks. Only later, when seizures were recorded with depth electrodes, did he report experiencing an epigastric sensation at the beginning of his attacks. He was observed to have swallowing movements, lip smacking, unresponsiveness, and automatisms. Neurological examination revealed right facial weakness, moderate right hemiparesis, and hemiatrophy with flexion deformity of the right hand. Full-scale I Q was 84; verbal IQ, 82; and performance IQ, 88. Skull roentgenograms showed a small left middle fossa with shift of the pineal to the left. A pneumoencephalogram showed evidence of an asymmetry of the cranial vault and typical bony changes associated with atrophy of the left hemisphere (see Fig 1B). Interictal scalp and sphenoidal EEG recordings showed bilateral temporal, independent sharp waves with left-sided predominance. Figure 5 shows the EEG recording of a complex partial seizure taken with scalp and sphenoidal elec- trodes. In two complex partial seizures recorded, the EEG seizure discharge seemed to arise from the right frontotemporal regions as rhythmic, slow 5-Hz activity, with definite predominance over the right temporal region and with phase reversals recorded primarily at T4. Ten to 12 seconds after seizure onset, the ictal discharge spread to the contralateral hemisphere. Because of the discrepancy between the clinical and radiological evidence of a left-sided cerebral lesion and the apparent right-sided seizure onset in the EEG, depth electrodes were stereotaxically implanted in both temporal lobes. Figure 6 illustrates the EEG tracing of a complex partial seizure recorded from depth electrodes. Five complex partial seizures were obtained with depth electrodes, and all showed onset of the ictal discharge in the left temporal lobe. A warning in the form of an epigastric sensation was followed 4 seconds later by a high-voltage rhythmic seizure discharge involving the left anterior and posterior hippocampal structures (LB 1-4 and LC 1-4); there was a simultaneous lowervoltage ictal discharge in the left amygdala. Seconds later, attenuation of background activity was recorded from the left anterior temporal neocortex (second, third, and fourth channels). Approximately 6 seconds after seizure onset, the discharge spread to the contralateral temporal lobe. In superficial temporal neocortical contacts, the seizure discharge was of higher amplitude on the right. In addition, with both extracranial and intracranial recordings, an asymmetrical disturbance of background activity was seen, with predominance over the damaged hemisphere. Stimulation studies using depth electrodes showed that the lowest threshold for evoking the patient's initial signs with associated afterdischarge was located in the left anterior hippocampus (1.5 mA). The lowest threshold for a seizure associated with loss of responsiveness was obtained with stimulation of the right amygdala at 2.5 mA. However, the more socially disabling seizures with automatisms and loss of con- Sammaritano et al: False Lateralitation by Surface EEG 365 Fig 6. Patient 2. Depth electrode electroencephalographicrecording of a complex partial seizure, obtained by telemetry. See text for description. (LC and RC = ldt and right posterior temporal lobe depth electrode strands, with deepest contacts in the parahip pocampal gyri; other abbreviations as in Figure 4.) sciousness required either bilateral temporal or right temporal lobe involvement. An anterior left temporal lobectomy, including the m y g dala and the anterior hippocampus, was carried out. At operation, the size of the sulci was increased, particularly the posterior superior extent of the sylvian fissure, and the hippocampus appeared indurated. Only a short recording from depth electrodes could be obtained with electrocorticography since the patient started vomiting. The only abnormality found before excision was an abnormal background activity over the left temporal region. Histological examination of the specimen showed subpial gliosis extending to the second cortical layer, with focal cortical necrosis in the cortex and white matter. After a 6-month postoperative period when he may have had either partial seizures or pseudoseizures, the patient has remained seizure-free for 13 years. Patient 3 A 30-year-old left-handed man suffered a head injury at age 6 months, lost consciousness, and developed a right hemiparesis. At age 14 years, he started having complex partial seizures. H e had an aura of fear and was observed to hum, moan, stare, and cough, and to exhibit occasional swallowing and lip-smacking movements, followed by unresponsiveness and automatisms. Neurological examination showed a mild right infantile hemiplegia with athetotic posturing of the right hand. Full-scale I Q was 100; verbal IQ, 96; and performance IQ, 103. Skull roentgenograms showed a small left middle fossa. A CT scan showed an enlarged left lateral ventricle and three small hypodensities in the posterior limb of the internal capsule on the left, suggestive of focal encephalomalacia and cerebral atrophy on that side (see Fig 1C). Scalp and sphenoidal EEG recordings showed bitemporal, 366 Annals of Neurology Vol 21 N o 4 April 1987 independent, interictal sharp waves with right-sided predominance. Figure 7 shows the EEG record of a typical complex partial seizure obtained with scalp and sphenoidal electrodes. All three complex partial seizures showed apparent seizure onset in the right temporal lobe. At seizure onset there was much chewing artifact, but generalized rhythmic discharge could be discerned. Definite predominance of epileptic discharge was recorded over the right inferomesial temporal region with phase reversals at SP2. Because of the discrepancy between the clinical and radiological evidence for a left-sided cerebral lesion, and the apparent right temporal lobe onset of the seizure discharge in the extracranial EEG, this patient was investigated with stereotaxically implanted depth electrode recordings obtained from both temporal and frontal lobes. A depth EEG recording of a complex partial seizure is shown in Figure 8. The seizure discharge started in the left temporal lobe (see a m in Figure 8), with attenuation of background activity recorded in the left amygdala (LA 1-3) and the left temporal neocortex (LA 3-5, LA 5-7, LB 3-5, LB 5-7) associated with rhythmic fast activity in the left hippocampus (LB 1-3). Two to 3 seconds after seizure onset, the ictal discharge spread to the right temporal lobe where high-voltage, fast rhythmic activity was recorded from the right amygdala (RA 1-3) and right hippocampus (RB 1-3), with a lower-voltage seizure discharge involving the right temporal neocortex (RA 3-5, RA 5-7, RB 3-5, RB 5-7). The seizure discharge also spread to both frontal regions. The epileptic abnormality recorded from the right hemisphere was of higher amplitude. Seizure onset was recorded from the left temporal lobe in all five complex partial seizures recorded with depth electrodes. In this patient, a bilateral background disturbance was seen with scalp and sphenoidal electrodes, and a left hemisphere predominance of this disturbance was seen with depth recordings. A left anterior temporal lobectomy was performed. Marked atrophy of the superior temporal gyms and hippocampus was found at operation. Preexcision electrocorticography showed moderately active spiking from the first Chewina S.C. 03-3934 Fig 7. Patient 3 . Extracranial EEG recording of a complex partial seizure, obtained with scalp and sphenoidal electrodes. See text for description. (Symbols for electrode positions as in Figures 2 and 5.) Seizure Onset S.C 84-0294 L ' ~~ Fig 8. Patient 3. Depth electrode recording o f a complex partial seizure, obtained telemetry. See text for description. (Abbreviations as in Figure 4.) Sammaritano et al: False Lateralization by Surface EEG 367 Summary of Scab and Sphenoidal and Depth Electrode Recordings for All 3 Patients ~~~ ~ Scalp EEGs Cerebral Lesion Patient 1, L vascular occlusion Patient 2, L vascular occlusion Patient 3, L head iniurv No. Interictal 9 Bitemporal, L>R 6 Bitemporal, L>R (416) (4/5) 6 Bitemporal, R>L (4/5) Depth EEGs Ictal Onset Background Disturbance No. InterictaI Right temporal (3 CPS) Right temporal (2 CPS) Right temporal (3 CPS) L>R 22 Bitemporal, L>R L>R 28 ... 25 Bitemporal, L=R (23) Bitemporal, (21) L>R (251 Ictal Onset Background Disturbance Left temporal (9 CPS) Left temporal (5 CPS) Left temporal ( 5 CPS) Bitemporal, L >R Bitemporal, L >R Bitemporal, L >R EEG = electroencephalogram; L = left; R = right; CPS = complex partial seizures. and second temporal Uri. Histological examination showed subpial gliosis of the cortex and white matter. During the 3 years following his operation, the patient has remained seizure-free. Discussion A summary of the EEG recordings for all patients with both extracranial scalp and sphenoidal electrodes and with depth electrodes is illustrated in the Table. In addition to the data showing left temporal lobe onset of complex partial seizures, left temporal lobe onset of ictal discharges associated only with multiple auras or with electrographic seizures without any clinical accompaniment was also recorded. The amplitude of ictal discharge was of higher amplitude over the right or more normal hemisphere in all patients. This may explain why, in scalp and sphenoidal EEG recordings, the onset of the ictal event appeared to arise from that side, thus yielding false lateralizing evidence of seizure onset. The difference in amplitude of the ictal discharge is most likely due to cerebral damage, which reduced the voltage of the ictal discharge on the side of the lesion. Evidence of increased cerebral destruction on that side, judging from background disturbance, was also noted during depth electrode recording, confirming the clinical and radiological evidence for such damage. In Patient 1, the higher amplitude of the discharges may have been partially due to a skull defect from the previous rightsided craniotomy. In patients with hemiparesis and seizures who are candidates for hemispherectomy, higher voltage and predominance of epileptic interictal discharge may also be recorded from the more normal hemisphere El}. It is of some interest that, in 2 of the 3 patients whose extracranially recorded ictal EEG discharge led to false lateralization, extracranially recorded interictal discharges predominated on the side of the onset of seizure discharge, as recorded with depth electrodes. The numbers are obviously too small to justify the 368 Annals of Neurology Vol 21 No 4 April 1987 conclusion that, in extracranial EEG recordings, interictal lateralizing evidence may be more reliable than ictal discharge, although a trend in this direction was discernible in an earlier study by Gloor and associates [37. These 3 cases emphasize the need for depth electrode exploration prior to surgery in patients whose lateralizing evidence derived from extracranial interictal EEG data conflicts with that obtained by extracranial ictal EEG recordings. In addition, evaluation with depth electrode recordings may be necessary when major conflicting evidence concerning lateralization and localization exists between extracranial EEG data and clinical or radiological evidence of a significant destructive brain lesion {G, 71. False lateralizing evidence of seizure onset can also at times be obtained during depth electrode recordings. Engel and Crandall121 and Spencer and colleagues 187 suggest that this may occur during anticonvulsant drug withdrawal, which may precipitate atypical seizures originating from areas distant from the primary epileptic focus. According to Marciani and associates 147, such cases are exceptional, and the occasional occurrence of such seizures from an area other than the habitual focus does not make such a patient unsuitable for surgical therapy. Engel and Crandall [ 2 ) concur with this view and state that such seizures with atypical onset recorded during drug withdrawal may not necessarily recur at other times. Why gross unilateral pathological changes may cause the appearance of bitemporal, independent, interictal epileptic discharges remains unclear. It may signify additional less severe contralateral brain damage or may represent an instance of secondary epileptogenesis, the so-called “mirror focus” phenomenon { 53. We suggest that, when seizures arise from an area of cortex that has sustained severe structural damage, the voltage of an ictal discharge may be reduced and difficult to detect at its onset in extracranial EEG recordings. When such a seizure discharge spreads from the damaged area to contralateral homologous regions that are more intact, this secondary contralateral discharge may be much higher in amplitude, as it arises from relatively healthy tissue. It may overshadow the seizure discharge arising from the area of actual seizure onset by so much that a false latetalizing diagnosis may be made from the extracranial EEG. *hen a gross structural lesion is known to exist, it should always be suspected that the patient's seizures arise from that side, even when some extracranial EEG evidence points to the contrary. In the presence of a gross focal cerebral lesion, recordings with scalp and sphenoidal electrodes may thus lead to false lateralization of tempotal epileptic discharges, if the recordings are not interpreted critically. Presented in part at the meeting of the American Epilepsy Society, San Francisco, CA, November 1984. References 1. Andermann F, Villemure JG, Tinuper P, Rasmussen T: Func- tional hemispherectomy. Neurology 36(suppl 1):327, 1986 2. Engel J Jr, Crandall PI-f: Falsely lotalizing ictal onset with depth EEG telemetry during anticonvulsant withdrawal. Epilepsia 24~344-355, 1983 3. Gloor P, Olivier A, Quesney LF, et ak The role of the limbic system in experiential phenomena of temporal lobe epilepsy. Ann Neurol 12:129-144, 1982 4. Marciani MG, Gotman J, Andermann F, Olivier A: Patterns of seizure activation after withdrawal of antiepileptic medication. Neurology 35:1437-1543, 1985 5. Morrell F Secondary epileptogenic lesions. Epilepsia 1:538-560, 1959160 6. Olivier A, Gloor P, Ives J: Investigation et traitement chirurgical de I'Cpilepsie bitemporale. L'Union MCdicale 109:1-4, 1980 7. Olivier A, Gloor P, Quesney LF, Andermann F The indications for and the role of depth electrode recordings in epilepsy. Appl Neurophysiol46:33-36, 1983 8. Spencer SS, Spencer DD, Williamson PD, Mattson RH: Ictal effects of anticonvulsant medication withdrawal in epileptic patients. Epilepsia 22:297-307, 1981 Sammaritano et al: False Lateralization by Surface EEG 369