Visual and quantitative ictal EEG predictors of outcome after temporal lobectomy

PURPOSE: We investigated whether visual and quantitative ictal EEG analysis could predict surgical outcome after anteromesial temporal lobectomy (AMTL) in which mesial structures, basal, and temporal tip cortex were resected. METHODS: We retrospectively reviewed 282 presurgical scalp-recorded ictal EEGs (21- to 27-channel) from 75 patients who underwent AMTL. We examined the pattern of seizure onset (frequency, distribution, and evolution) and estimated the principal underlying cerebral generators by using a multiple fixed dipole model that decomposes temporal lobe activity into four sublobar sources (Focus 1.1). We correlated findings with a 2-year postoperative outcome. RESULTS: Sixteen patients had seizures with a well-lateralized, regular 5 to 9-Hz rhythm at onset, that most often had a temporal or subtemporal distribution. All patients became seizure free after surgery. In 51 patients, seizure onset was remarkable for lateralized slow rhythms (<5 Hz), which sometimes appeared as periodic discharges, were often irregular and stable only for short periods (<5 s), and had a widespread lateral temporal distribution. Among these a favorable surgical outcome was encountered in patients with seizures having prominent anterior-tip sources ( 16 of 17 seizure free), whereas those with dominant lateral or oblique sources had a less favorable outcome (three of 14 and 13 of 18, respectively). Irregular, nonlateralized slowing characterized seizure onsets in eight patients. Three patients became seizure free after surgery. CONCLUSIONS: Both visual and quantitative sublobar source analysis of scalp ictal EEG can predict surgical outcome in most cases after AMTL and complement non-invasive presurgical evaluation.     

EEG findings in frontal lobe epilepsies

As a group, epilepsies of frontal lobe origin are thought to be poorly localized using surface EEG recordings. This finding may depend on the specific areas of frontal lobe from which the seizures originate or the pathologic substrate. We reviewed the presurgical surface EEGs of patients with frontal lobe epilepsy who underwent epilepsy surgery. The specific area of the frontal lobe where seizures originated was determined by 1) intracranial ictal EEG recordings, or 2) the presence of a structural lesion, identified by imaging studies in patients who achieved complete seizure control following surgery. We differentiated patients whose seizures began in the dorsolateral frontal convexity from those whose seizures began in the medial frontal region, and we correlated EEG findings in the interictal, postictal, and ictal states with seizure semiology, pathologic substrate, and surgical outcome. Four of nine patients had seizures originating in the dorsolateral frontal convexity and five had medial frontal onset seizures. Patients whose seizures originated from the dorsolateral convexity had focal interictal epileptiform abnormalities that localized to the region of seizure onset. Patients whose seizures began in the medial frontal region had either no interictal epileptiform abnormality or had multifocal epileptiform discharges. Patients whose seizures began in the dorsolateral convexity showed focal electrographic seizure activity that was localizing. This rhythmic fast activity did not appear to be substrate-specific. Patients whose seizure onset localized to the medial frontal region did not show focal electrographic seizure at clinical onset. We conclude that the scalp EEG recordings of frontal lobe epilepsies contain features that enable differentiation of seizures originating from two different regions of the frontal lobe.     

Ictal cerebral blood flow in seizures originating in the posterolateral cortex

In selecting patients for epilepsy surgery, it is important to distinguish mesial temporal seizures from seizures originating in the posterolateral cortex. We studied ictal cerebral perfusion in five patients with complex partial seizures with clear posterior EEG ictal onsets and clinical seizures semiology suggesting seizure origin in the posterolateral cortex. METHODS: Ictal SPECT was performed during video EEG monitoring using 99mTc-HMPAO as a cerebral perfusion tracer and a rotating gamma camera to acquire images. RESULTS: Three patterns of ictal hyperperfusion were seen: pattern A = temporoparieto-occipital junction extending into the lateral temporal cortex, involving the mesial temporal cortex and basal ganglia to a lesser degree and a small area of hyperperfusion in the contralateral parietal cortex (two patients); pattern B = pattern A but with no hyperperfusion of the mesial temporal cortex (one patient); and pattern C = localized hyperperfusion in the area of the temporoparieto-occipital junction (two patients). CONCLUSION: Our results suggest distinct patterns of ictal perfusion in seizures with posterolateral ictal EEG onsets. Ictal SPECT may be useful in distinguishing such seizures.     

Dipole source localization of ictal epileptiform activity

Dipole source localization of ictal epileptiform activity recorded by scalp EEG was performed in patients prior to surgical treatment. The dipole tracing method combined with the scalp-skull-brain head model was used to locate epileptogenic foci. A digital EEG system was used for data collection. The accuracy of dipole source localization was evaluated by comparing the focus location with that obtained by chronic subdural electrocorticography. In a case of frontal lobe epilepsy with epileptogenic focus in the frontoparietal convexity, the results of dipole source localization agreed well with those obtained with chronic subdural electrocorticography. In a case of lateral temporal lobe epilepsy, the results of dipole source localization were consistent with those obtained with chronic subdural electrocorticography, but a small localization error was observed. The clinical usefulness of and suggestions for improving this method are discussed.     

Clinical and electrographic manifestations of lesional neocortical temporal lobe epilepsy

To determine whether lesional neocortical temporal lobe epilepsy (NTLE) can be differentiated from mesial temporal lobe epilepsy (MTLE) during the noninvasive presurgical evaluation, we compared the historical features, seizure symptomatology, and surface EEG of 8 patients seizure free after neocortical temporal resection with preservation of mesial structures and 20 patients after anterior temporal lobectomy for MTLE. Seizure symptomatology of 107 seizures (28 NTLE, 79 MTLE) was analyzed. One hundred one ictal EEGs (19 NTLE, 82 MTLE) were reviewed for activity at seizure onset; presence, distribution, and frequency of lateralized rhythmic activity (LRA); and distribution of postictal slowing. Seizure symptomatology and EEG data were compared between groups, and sensitivity, specificity, and positive and negative predictive values were determined for variables that differed significantly. Multiple logistic regression was used to determine whether patients could be correctly classified as having MTLE or NTLE. MTLE patients were younger at onset of habitual seizures and more likely to have a prior history of febrile seizures, CNS infection, perinatal complications, or head injury. NTLE seizures lacked features commonly exhibited in MTLE, including automatisms, contralateral dystonia, searching head movements, body shifting, hyperventilation, and postictal cough or sigh. NTLE ictal EEG recordings demonstrated lower mean frequency of LRA that frequently had a hemispheric distribution, whereas LRA in MTLE seizures was maximal over the ipsilateral temporal region. We conclude that it may be possible to differentiate lesional NTLE from MTLE on the basis of historical features, seizure symptomatology, and ictal surface EEG recordings. This may assist in the identification of patients with medically refractory nonlesional NTLE who frequently require intracranial monitoring and more extensive or tailored resections.     

Repair of traumatic orbital wall defects with nasal septal cartilage: report of five cases

PURPOSE: Arachnoid cysts are sometimes encountered in MRIs performed for a variety of reasons. In patients with epilepsy, particularly those with refractory epilepsy, arachnoid cysts are often assumed to be related to their seizure focus. We conducted a study to investigate this putative relationship. METHODS: A retrospective study on the incidence of arachnoid cysts was performed in patients seen in our Epilepsy Clinic who had CT or MRI scans, interictal EEGs or ictal EEGS. Locations of seizure foci in these patients were defined from clinical and electrophysiologic data. RESULTS: Seventeen of 867 patients had arachnoid cysts. Twelve patients had temporal lobe cysts and only 3 of them had temporal lobe seizures. Four patients had frontal lobe cysts and only 1 had frontal lobe seizures ipsilateral to the cyst. One patient had a cerebello-pontine angle cyst and frontal lobe seizures. Thus, clinical manifestations of seizures and EEG findings (interictal and/or ictal) indicated that the seizure focus was adjacent to the cysts in only 4 patients (23.5%). CONCLUSIONS: Our findings suggest that arachnoid cysts are often an incidental finding in patients with epilepsy and do not necessarily reflect the location of the seizure focus.     

Ictal single photon emission computed tomography in occipital lobe seizures

PURPOSE: Ictal single photon emission computed tomography (SPECT) has been evaluated as an adjunctive localizing technique in temporal lobe epilepsies and, to a lesser degree, in some extratemporal epilepsies. The purpose of this study was to determine whether occipital lobe seizures are associated with distinctive ictal cerebral blood perfusion (rCP) patterns. METHODS: SPECT was used with the tracer 99mTc HMPAO to image ictal rCP in 6 patients in whom clinical, EEG, and imaging data indicated occipital lobe seizures. RESULTS: Two patterns of rCP were seen. Four patients had hyperperfusion that was restricted to the occipital lobe, and two patients had hyperperfusion of the occipital lobe and the ipsilateral mesial temporal lobe, with hypoperfusion of the lateral temporal lobe. The latter 2 patients had clinical and surface EEG evidence of temporal lobe involvement in the seizure discharge. CONCLUSIONS: Ictal rCP patterns in occipital lobe seizures are distinct from those in temporal lobe seizures and may vary according to whether or not ipsilateral temporal lobe structures are involved in the ictal discharge.     

In vivo cerebral metabolism and central benzodiazepine-receptor binding in temporal lobe epilepsy

Positron emission tomography measured interictal cerebral glucose metabolism with [18F]fluorodeoxyglucose and central benzodiazepine-receptor binding with [11C]flumazenil in 10 mesial temporal lobe epilepsy (TLE) patients and in normal subjects. Eight TLE patients had mesial temporal, lateral temporal, and thalamic hypometabolism ipsilateral to EEG ictal onsets, with additional extratemporal hypometabolism in four. One had unilateral anterior mesial temporal hypometabolism only, and one had normal metabolism. Each patient had decreased benzodiazepine-receptor binding in the ipsilateral anterior mesial temporal region, without neocortical changes. Thus, interictal metabolic dysfunction is variable and usually extensive in TLE, whereas decreased central benzodiazepine-receptor density is more restricted to mesial temporal areas. Metabolic patterns in TLE may reflect diaschisis, while benzodiazepine-receptor changes may reflect localized neuronal and synaptic loss that is specific to the epileptogenic zone. [11C]Flumazenil imaging may be useful in presurgical evaluation of refractory complex partial seizures.     

Association of combined MRI, interictal EEG, and ictal EEG results with outcome and pathology after temporal lobectomy

PURPOSE: Magnetic resonance imaging, interictal scalp EEG, and ictal scalp EEG each have been shown to localize the primary epileptic region in most patients with mesial-basal temporal lobe epilepsy (MBTLE), but the association of surgical outcome and pathology with each combination of these test results is not known. METHODS: We reviewed the MRI, interictal scalp EEG, and ictal scalp EEG results of 90 consecutive patients with MBTLE. Twelve patients were excluded from the analysis because inconclusive bitemporal intracranial EEG results precluded anterior temporal lobectomy (ATL); none had concordant MRI and interictal scalp EEG results. We compared all combinations of presurgical MRI, interictal EEG, and ictal EEG results to seizure outcome and tissue pathology in the 78 patients who underwent an ATL. RESULTS: Forty-eight (61%) patients had concordant lateralized MRI and interictal EEG temporal lobe abnormalities, with no discordant ictal EEG results; 77% of these patients were seizure-free after ATL. Concordance of MRI and interictal EEG abnormalities correlated with seizure cessation (p < 0.05), compared to all combinations with discordant or nonlateralizing MRI and interictal EEG results. Mesial temporal sclerosis (MTS) was confirmed pathologically in about 80% of both groups (p = 0.5). Outcome in patients with concordant MRI and ictal EEG with nonlateralizing interictal EEG was significantly worse than combinations with concordant MRI and interictal EEG (p < 0.02). CONCLUSIONS: Compared to other combinations of test results, concordance of MRI and interictal EEG is most closely associated with surgical outcome in MBTLE. However, most selected patients have pathologic confirmation of MTS regardless of test results or outcome. This information may be useful for planning the presurgical evaluation of patients with medically intractable MBTLE.     

Postictal nose wiping: a lateralizing sign in temporal lobe complex partial seizures

We report postictal nose wiping as a postictal symptom of localizing and lateralizing significance in focal epilepsy. We reviewed videotapes of 444 focal seizures in 101 patients who underwent prolonged video and EEG monitoring during presurgical epilepsy evaluation, and observed postictal nose wiping in 51.3% of 76 patients with temporal lobe epilepsy. The hand used to perform postictal nose wiping was ipsilateral to the side of seizure origin in 86.5% of all seizures and in 97.3% of all patients. We conclude that postictal nose wiping is a common, easily assessed symptom after focal seizures of temporal lobe origin that provides reliable lateralizing information on the side of seizure onset.     

Medial temporal lobe epilepsy: videotape analysis of objective clinical seizure characteristics

PURPOSE: The syndrome of temporal lobe epilepsy has been described in great detail. Here we focus specifically on the clinical manifestations of seizures originating in the hippocampus and surrounding mesial temporal structures. METHODS: Seizure origin was confirmed in 67 cases by depth EEG recording and surgical cure after mesial temporal resection. RESULTS: Among nonlateralized manifestations, we commonly found oral automatisms, pupillary dilatation, impaired consciousness, and generalized rigidity. Appendicular automatisms were often ipsilateral to the seizure focus, whereas dystonia and postictal hemiparesis were usually contralateral. Head deviation, when it occurred early in the seizure, was an ipsilateral finding, but was contralateral to the seizure focus when it occurred late. Clear ictal speech and quick recovery were found when seizures originated in the non-language-dominant hemisphere, but postictal aphasia and prolonged recovery time were characteristic of seizure origin in the language-dominant hemisphere. CONCLUSIONS: These signs help to define the mesial temporal lobe epilepsy (MTLE) syndrome and often provide information as to the side of seizure origin.     

Preictal SPECT in temporal lobe epilepsy: regional cerebral blood flow is increased prior to electroencephalography-seizure onset

Peri-ictal SPECT provides unique information on the dynamic changes in regional cerebral blood flow (rCBF) that occur during seizure evolution and, thus, could be useful in clarifying the poorly understood interplay of the interictal and ictal states in human focal epilepsy. The regional hyperperfusion observed on ictal SPECT is generally believed to be a consequence of electrical seizure activity. However, recent studies using invasive long-term cortical CBF monitoring have demonstrated that rCBF changes occur up to 20 min prior to ictal electroencephalography (EEG) onset. Because of apparent technical difficulties, no preictal SPECT studies have been reported so far. Therefore, we present our results on two patients with temporal lobe epilepsy in whom preictal SPECT scans were performed fortuitously under continuous video-EEG monitoring control. METHODS: Technetium-99m-hexamethyl propyleneamine oxime was injected 11 min (Patient 1) and 12 min (Patient 2) before clinical and EEG seizure onset, as documented from simultaneous video-EEG monitoring in two patients with temporal lobe epilepsy. We obtained accurate anatomical reference of CBF changes visible on SPECT by a special coregistration technique of MRI and SPECT. RESULTS: Whereas interictal SPECT showed a hypoperfusion of the temporal lobe ipsilateral to the seizure focus, on preictal SPECT, a significant increase in rCBF in the epileptic temporal lobe could be observed. These rCBF changes were not accompanied by any significant changes of the ongoing EEG. CONCLUSION: Our study provides evidence that rCBF is increased in the epileptic temporal lobe several minutes before EEG seizure onset. Thus, rCBF changes observed on peri-ictal SPECT scan cannot be considered a mere consequence of EEG seizure activity but may rather reflect a change in neuronal activity precipitating the transition from the interictal to the ictal state.     

A stereoelectroencephalographic (SEEG) study of light-induced mesiotemporal epileptic seizures

PURPOSE: This study explored the mechanism of light-induced complex partial seizures by using ictal intracerebral recordings in a patient with refractory epilepsy of the right temporal lobe. METHODS: Presurgical evaluation of this patient was realized by means of video-EEG recordings, WADA test, magnetic resonance imaging (MRI), F18-deoxyglucose and C11-flumazenil positron emission tomography (PET) interictal neuroimaging data, and stereoelectroencephalographic (SEEG) ictal recordings. RESULTS: SEEG investigations demonstrated the right mesiotemporal origin of all the patient's seizures. This result was confirmed by a successful right temporal lobectomy. Moreover, SEEG recordings revealed a frequent interictal spiking activity in the right occipital visual cortex that was undetectable on scalp recordings. However, the occipital cortex was not involved at the onset of mesiotemporal ictal discharges and was not hyperresponsive to focal electrical stimulation. CONCLUSIONS: This study shows that, in spite of interictal occipital spiking, the photosensitivity of mesiotemporal seizures can be observed in both the absence of occipital cortex involvement during ictal discharges and demonstrable hyperexcitability of the occipital cortex to light or direct electrical stimulation.     

Pedicled and microvascular reanastomosed transplants for reconstruction in the head-neck area

In seizures starting gradually, careful examination of the background is required to determine the time and region of onset. We propose a method for displaying EEG variables which characterize seizure onset: changes in amplitude and in average frequency compared to background. These variables are displayed topographically for each EEG channel so that 1 or 2 min of EEG may be viewed on a standard screen, thus representing pre-ictal and ictal periods. We evaluated the ability of this display to indicate seizure onset, by comparing the times and regions of seizure onset indicated by traditional EEG and by the display. The comparison was performed on 30 seizures from scalp recordings and 49 seizures from depth recordings. Seizures were selected for having a gradual onset with no or minimal artefact. Onset times from traditional EEG and the computer method, examined independently, coincided (within 3 sec) in 77% of scalp seizures and 63% of depth seizures. In 14% of seizures the computer display indicated an onset more than 3 sec earlier than visual examination; upon reexamination, however, this onset was thought to be possibly correct. This quantitative display, which in practice should be used with traditional EEG, may thus be useful for computer-assisted seizure interpretation and for a condensed representation of seizures.     

Direct isolation, phenotyping and cloning of low-frequency antigen-specific cytotoxic T lymphocytes from peripheral blood

A 21-year-old male presented with temporal lobe epilepsy associated with a venous angioma in the ipsilateral frontal lobe, presenting as intractable complex partial seizures. Neuroimaging showed a cerebral venous angioma in the right dorsolateral and opercular frontal lobe, and atrophy of the right hippocampus. As the ictal electroencephalogram (EEG) obtained with subdural electrodes indicated spike discharges initiating from the right mesial temporal lobe, temporal lobectomy was performed. The patient was seizure-free after the operation. Patients with epilepsy who have a cerebral venous angioma require precise analysis of the seizure pattern and an ictal EEG because of cerebral venous angioma may be associated with an another epileptogenic lesion which is surgically treatable.     

Malignant lesions presenting as symptoms of craniomandibular dysfunction

We compared the findings of scalp electroencephalogram with subdural electrode array (SEA) recordings in 19 patients with refractory frontal lobe epilepsy. Prolonged scalp interictal recordings localized the epileptogenic zone in 12 patients; seven had no interictal sharp waves. The SEAs showed multifocal interictal sharp waves in all patients. Seven patients with localized seizure onset on scalp recording showed extensive ictal onset on the SEA recording. Five patients with lateralized seizure onset to one hemisphere on scalp recording were found to have ictal onset on SEA restricted to a smaller area. Because of the large epileptogenic zone found on SEA recordings, a complete resection was possible in only five (33%) of the 15 patients who had resections. Eight (53%) of the 15 patients benefited from surgery (mean follow-up, 4.6 years). The SEAs also allowed functional localization in most patients. From these data, we suggest that a localizing scalp electroencephalogram in patients with frontal lobe epilepsy may be misleading because SEA recordings show larger epileptogenic zones than anticipated. Furthermore, we postulate that the larger extensive epileptogenic zone may account for the poorer surgical outcome in patients with frontal lobe epilepsy compared with patients with temporal lobe epilepsy.     

"Periodic" seizures

PURPOSE: To describe regularly recurring ictal phenomena as recorded in a single patient whose seizure disorder related to a left temporal cavernous angioma. METHODS: Seizures were recorded by left temporal subdural strip electrodes which were bilaterally placed because of ambiguous seizure origin and right temporal memory dysfunction at Wada testing. Seizure length, interseizure intervals, and interseizure onset intervals were visually assessed. The coefficient of variation was used as an estimate of variability in seizure periodicity. RESULTS: Mean seizure durations varied from 68 to 95 s; coefficients of variation varied from 0.08 to 0.18, values similar to other periodic biological phenomena. Mean daily seizure intervals varied from 96 to 152 s with coefficients of variation ranging from 0.12 to 0.35. Interseizure onset intervals had smaller coefficients of variation (0.03-0.20). Manifestations of these simple partial seizures included a rising epigastric sensation and nausea. CONCLUSIONS: Previously described periodic EEG phenomena are interictal events or appear with peripheral events of similar cadence. Therefore, we remain unaware of any documentation of periodic ictal electrographic events. The restricted propagation and duration of these recorded seizures may have simplified their pathophysiology allowing a stereotyped involvement of excitatory and inhibitory mechanisms producing the periodicity.     

Alumina gel injections into the temporal lobe of rhesus monkeys cause complex partial seizures and morphological changes found in human temporal lobe epilepsy

The goal of the present study was to determine whether alumina gel injections into temporal lobe structures cause complex partial seizures (CPS) and pathological changes observed in human temporal lobe epilepsy. Rhesus monkeys with alumina gel injections in the amygdala, perirhinal and entorhinal cortices, or Ammon's horn and dentate gyrus all initially displayed focal pathological electroencephalographic (EEG) slowing limited to the site of injection. After clinical seizures developed, they also displayed widespread pathological EEG slowing over both hemispheres, interictal and ictal epileptiform EEG abnormalities limited to the mesial-inferior temporal lobe on the side of injection, and different degrees of spread to other ipsilateral and contralateral structures. Noninjected control and nonepileptic monkeys with injections into the middle and inferior temporal gyri displayed no hippocampal neuronal loss or mossy fiber sprouting. When alumina gel was injected into the amygdala, CPS began within 3-6 weeks and degeneration of neurons and gliosis occurred in the perirhinal cortex or the hippocampus, with consequent sprouting of mossy fibers in the dentate gyrus. Dispersion of the granule cell layer was also observed. Other monkeys with alumina gel in the perirhinal and entorhinal cortices developed CPS within 2-3 weeks after the injections and displayed mossy fiber sprouting only after 4 weeks after the injections. Alumina gel in Ammon's horn and the dentate gyrus also induced CPS, but mossy fiber sprouting was limited to sites immediately adjacent to the injection, probably because none survived more than 4 weeks after the injections. This nonhuman primate model of CPS displayed similar anatomical, behavioral, and EEG features as observed in human temporal lobe epilepsy and provides opportunities to analyze the chronological sequence of epileptogenesis and to test potential therapies.     

Routine microbiological testing in sudden and unexpected infant death

We reviewed 187 depth recorded seizures in 33 patients with non-lesional temporal lobe complex partial seizures. All patients had a minimum of 1 year follow-up following temporal lobectomy. We classified seizure onset pattern as rhythmic activity, attenuation, or repetitive spikes or spike wave complexes. The most common pattern of seizure onset was rhythmic activity and the next most common pattern was repetitive spikes. Seventy-five seizures (49%) had only one seizure onset pattern, and 79 seizures (51%) had a combination of seizure onset patterns. The degree of hippocampal gliosis strongly predicted the type of seizure onset pattern (Chi square = 24.07, 2 d.f., P < 0.01). The rhythmic activity pattern was associated with mild gliosis, and the repetitive spike pattern was associated with severe gliosis. We classified seizure onset as focal or regional based on the number of electrode contacts that were involved by the ictal EEG. A focal seizure onset was associated with an excellent outcome following temporal lobectomy.     

Rhodamine 123 efflux modulation in the presence of low or high serum from CD56+ hematopoietic cells or CD34+ leukemic blasts by B9309-068, a newly designed pyridine derivative

BACKGROUND: Although magnetoencephalography (MEG) provides accurate information on the spatial distribution and temporal patterns of the "interictal" epileptic activities, it is interictal in nature and therefore also prone to all the problems associated with interictal data. METHODS: We investigated the subclinical "ictal" epileptic activity with a 37-channel, large-array biomagnetometer and mapped the data onto a three-dimensional image in a patient with intractable frontal lobe epilepsy. Dipole source localization was calculated based on magnetic fields for both the interictal and subclinical ictal activities. RESULTS: The current dipoles of the interictal MEG spikes (MEG irritative zone) were revealed to be scattered in the left anterior frontal lobe, whereas that of the subclinical ictal onset (MEG subclinical ictal onset zone) was surrounded by the interictal dipole cluster. The dipole source localization of the propagating activities was not calculated with a single dipole model. The MEG subclinical ictal onset zone correlated well with the ictal onset zone subsequently recorded by invasive subdural electrophysiological monitoring. After multiple subpial transection of the deduced epileptogenic area, a dramatic reduction of the seizures occurred. CONCLUSION: These results illustrate the potential of MEG for localizing the epileptogenic foci with high spatial and temporal resolution.