Ictal video-EEG Research Articles

Temporal lobe epilepsy and emotion recognition without amygdala: a case study of Urbach‐Wiethe disease and review of the literature

We describe the epilepsy features and emotion recognition abilities (recognition of basic facial emotions and recognition of emotional prosody) in a patient with Urbach-Wiethe disease with bilateral amygdala calcifications. Our data, supported by ictal video-EEG recording, indicated that our patient suffered from mesial temporal lobe epilepsy. Emotion recognition abilities were compared to those of healthy controls and those of patients with bilateral mesial temporal lobe epilepsy. Our patient showed a selective impairment of the recognition of facial expression of fear, whereas recognition of emotional prosody was preserved, in contrast to bilateral mesial temporal lobe epilepsy patients that presented with deficits in both domains. We also reviewed the literature on epilepsy in Urbach-Wiethe disease (41 patients). Our findings suggest that in Urbach-Wiethe disease, the circumscribed damage of both amygdalae results in a selective dysfunction of fearful face processing, in contrast to bilateral mesial temporal lobe epilepsy patients who present with a widespread and multimodal impairment in the judgement of emotional stimuli.

Ictal injury in psychogenic non-epileptic seizures

PurposeWhilst ictal injuries in psychogenic non-epileptic seizures (PNES) have been reported previously, very few studies have described the spectrum of ictal injuries in these patients. In the current study, we tried to determine the spectrum of reported ictal injuries associated with PNES and to investigate the possible associated risk factors. MethodsAll patients with PNES were recruited prospectively in the outpatient epilepsy clinic at Shiraz University of Medical Sciences, between 2008 and 2013. The diagnosis was made by clinical assessment and ictal video-EEG recordings. We asked all patients and their caregivers about history of any minor (e.g., tongue biting, bruises, and lacerations) or major (e.g., burns and fractures) physical injuries associated with their seizures, since their disease started. Clinical variables, factors potentially predisposing to PNES and video-EEG recordings of all patients were analyzed. ResultsTwo hundred and eleven patients were studied. Sixty-five patients (30.8%) reported injuries with one or more of their attacks. The most common type of reported injury was tongue biting. Lacerations, bruises, limb fractures, dental injury, and burn were also reported. ConclusionPNES commonly produce physical injuries. Despite the shibboleth that injuries rarely occur during PNES, mild injuries commonly happen and even severe injuries such as fractures and burns are not uncommonly reported in these patients. Patients with more dramatic seizure manifestations (e.g., urinary incontinence) were more likely to report ictal injuries.

Ictal kissing behavior: Neurological and psychodynamic overview

This study is based on the psychodynamic and neurological analysis of three Turkish patients who displayed ictal kissing automatism during their seizures. To unveil the probable underlying causes of their kissing behaviors, all patients underwent psychiatric interviews after being evaluated by ictal video-EEG recordings. The group consisted of two females (ages 35 and 29) and one male (age 26). In addition to prominent oral automatisms, each patient also displayed behaviors of kissing or blowing kisses to individuals at close proximity. Seizures were related to the right temporal lobe in two patients and the left temporal lobe in one patient. Magnetic resonance imaging showed mesial temporal sclerosis in two of the patients (one left, one right) and was normal in one. According to the DSM-IV-TR criteria, each of the three patients also suffered from major depression, while the psychodynamic interviews revealed traumatic childhood histories and intense unfulfilled affective needs.

α-[ 11 C]-Methyl- l -tryptophan–PET in 191 patients with tuberous sclerosis complex

This was an observational study done on a large cohort of patients with tuberous sclerosis complex (TSC) to determine whether i) the presence of α-[(11)C]-methyl-l-tryptophan (AMT) hotspots is related to the duration of seizure intractability, ii) the presence of AMT hotspots is related to specific TSC gene mutations, and iii) there is concordance between areas with an AMT hotspot and seizure lateralization/localization on scalp EEG. One hundred ninety-one patients (mean age: 6.7 years; median: 5 years; range: 3 months to 37 years) with TSC and intractable epilepsy were included. All patients underwent AMT-PET scan. AMT uptake in each tuber and normal-appearing cortex was measured and correlated with clinical, scalp EEG, and, if available, electrocorticographic data. The longer the duration of seizure intractability, the greater the number of AMT hotspots (r = 0.2; p = 0.03). AMT hotspots were seen in both TSC1 and TSC2. There was excellent agreement in seizure focus lateralization between ictal scalp EEG and AMT-PET (Cohen κ 0.94) in 68 of 95 patients in whom both ictal video-EEG and AMT-PET showed lateralizing findings; in 28 of 68 patients (41%), AMT was more localizing. Furthermore, AMT-PET was localizing in 10 of 17 patients (58%) with nonlateralized ictal EEG. AMT-PET, when used together with video-EEG, provides additional lateralization/localization data, regardless of TSC mutation. The duration of seizure intractability may predict the multiplicity of areas with AMT hotspots.

Dravet syndrome: New potential genetic modifiers, imaging abnormalities, and ictal findings

Dravet syndrome is an autosomal dominant epileptic encephalopathy of childhood, which is caused mainly by SCN1A and PCHD19 mutations. Although Dravet syndrome is well recognized, the causes of acute encephalopathy are still elusive, and reported data on ictal electroencephalography (EEG) and structural brain abnormalities are scarce. We studied 30 children who fulfilled the clinical criteria for Dravet syndrome. All patients were screened for SCN1A mutations and 25 for POLG mutations with bidirectional sequencing. Clinical data, including etiologic studies done as part of the clinical workup, were collected from hospital charts. Ictal video-EEG recordings and magnetic resonance (MR) images were reanalyzed by the authors. SCN1A mutations were found in 25 patients (83%). Two SCN1A mutation-negative patients had chromosomal translocations involving chromosomes 9 and X, and one had a mutation in PCDH19. Prolonged seizures were associated with acute encephalopathy in three SCN1A mutation-positive patients. One showed evidence of a significant hypoxic-ischemic event during status epilepticus. The other two demonstrated new persistent neurologic deficits postictally; they both carried heterozygous POLG variants (p.Trp748Ser or p.Gly517Val). Hippocampal sclerosis or loss of gray-white matter definition in the temporal lobe was observed in 7 of 18 patients who had MRI after age 3 years (39%). Motor seizures were recorded on video-EEG for 15 patients, of whom 12 were younger than 6 years at recording; 11 patients (73%) showed posterior onsets. Our data imply that a heterozygous X;9 translocation and rare POLG variants may modify the clinical features of Dravet syndrome. The latter may increase susceptibility for acute encephalopathy. Temporal lobe abnormalities are common in patients imaged after 3 years of age. Focal seizures seem to localize predominantly in the posterior regions in young children with Dravet syndrome.

Quantifying the contribution of video in combined video-magnetoencephalographic ictal recordings of epilepsy patients

Magnetoencephalography (MEG) measures magnetic fields generated by neuronal currents. MEG is complementary to EEG. Considerable body of evidence indicates that ictal MEG recordings can provide useful information for pre-surgical evaluation of epilepsy patients alongside the more established long-term ictal video-EEG. Ictal MEG is recorded in some epilepsy surgery centers. However, a wider adoption of ictal MEG is hampered by lack of tools for synchronized video-MEG recording similar to those of video-EEG. We have augmented MEG with a synchronized behavioral video-recording system. To estimate its additional value in ictal recordings, we retrospectively analyzed recordings of 10 epilepsy patients with and without the video. In six patients out of ten, adding the video substantially changed the resulting interpretations. In all six cases the effect was considerable: the number of detected seizures changed by more than 50%. Synchronized video and audio recording capabilities are important for effective ictal MEG recordings of epilepsy patients.

Long-term outcome after callosotomy or vagus nerve stimulation in consecutive prospective cohorts of children with Lennox–Gastaut or Lennox-like syndrome and non-specific MRI findings

PurposeThere is currently no resective (potentially curative) surgical option that is useful in patients with Lennox–Gastaut syndrome. Palliative procedures such as callosotomy (Cx), vagus nerve stimulation (VNS) or deep brain stimulation have been offered. We compared the outcomes after Cx or VNS in two consecutive prospective cohorts of patients with generalised epilepsy. MethodsTwenty-four patients underwent callosotomy from 2006 to 2007 (Group 1); 20 additional patients were submitted to VNS from 2008 to 2009 (Group 2). They had generalised epilepsy of the Lennox–Gastaut or Lennox-like type. They were submitted to a neurological interview and examination, interictal and ictal video-EEG, high resolution 1.5T MRI, and cognitive and quality of life evaluations. The two-year post-operative follow-up results were evaluated for each patient. ResultsThe final mean stimuli intensity was 3.0mA in the Group 2 patients. Seizure-free patients accounted for 10% in Group 1 and none in Group 2. Ten and sixteen percent of the Group 1 and 2 patients, respectively, were non-responders. Improvements in attention and quality of life were noted in 85% of both Group 1 and 2 patients. Rupture of the secondary bilateral synchrony was noted in 85% of Group 1 patients; there was no EEG modification after VNS in Group 2. Both procedures were effective regarding the control of atypical absences and generalised tonic–clonic seizures. Both procedures were not effective in controlling tonic seizures. Callosotomy was very effective in reducing the frequency of atonic seizures, but VNS was ineffective. In contrast, callosotomy was not effective in reducing myoclonic seizures, whereas VNS was. DiscussionCallosotomy might be preferred as the primary treatment in children with Lennox–Gastaut syndrome, and no specific findings on MRI if atonic seizures prevail in the patient's clinical picture; when myoclonic seizures prevail, the same might hold true in favour of VNS. When atypical absence or generalised tonic–clonic seizures are the main concern, although both procedures carry similar effectiveness, VNS might be considered a good option as an initial approach, taking into account the adverse event profile. Patients should be advised that both procedures are not very effective in the treatment of tonic seizures.

Focal seizures with affective symptoms are a major feature of PCDH19 gene–related epilepsy

Mutations of the protocadherin19 gene (PCDH19) cause a female-related epilepsy of variable severity, with or without mental retardation and autistic features. Despite the increasing number of patients and mutations reported, the epilepsy phenotype associated with PCDH19 mutations is still unclear. We analyzed seizure semiology through ictal video-electroencephalography (EEG) recordings in a large series of patients. We studied 35 patients with PCDH19 gene-related epilepsy and analyzed clinical history and ictal video-EEG recordings obtained in 34 of them. Clusters of focal febrile and afebrile seizures had occurred in 34 patients, at a mean age of 10 months. The predominant and more consistent ictal sign was fearful screaming, occurring in 24 patients (70.5%); it was present since epilepsy onset in 12 and appeared later on, during the course in the remaining 12 patients. In infancy, fearful screaming mainly appeared within the context of seizures with prominent hypomotor semiology, whereas during follow-up it was associated with prominent early motor manifestations. In 16 patients, seizures were video-EEG recorded both at onset and during follow-up: in five patients (31%) seizure semiology remained identical, in 7 (44%) semiology varied and in four patients it was unclear whether ictal semiology changed with age. Three patients (9%) had both focal and generalized seizures, the latter consisting of absences and myoclonus. Ictal EEG during focal seizures showed a prominent involvement of the frontotemporal regions (22 patients). About 45% of patients had an alternating EEG pattern, with the ictal discharge migrating from one hemisphere to the contralateral during the same ictal event. Status epilepticus occurred in 30% of patients. Cognitive impairment occurred in 70%, ranging from mild (42%) to moderate (54%) and severe (4%); autistic features occurred in 28.5%. Direct sequencing detected 33 different heterozygous candidate mutations, 8 of which were novel. Mutations were missense substitutions (48.5%), premature termination (10 frameshift, 4 nonsense, and 2 splice-site mutations; 48.5%), and one in-frame deletion. Thirty candidate mutations (91%) were de novo. No specific genotype-phenotype correlation could be established, as missense and truncating mutations were associated with phenotypes of comparable severity. Most patients with PCDH19 mutations exhibit a distinctive electroclinical pattern of focal seizures with affective symptoms, suggesting an epileptogenic dysfunction involving the frontotemporal limbic system. Awareness of this distinctive phenotype will likely enhance recognition of this disorder.

Late‐onset epileptic spasms may be cured by focal cortical resective surgery

We report the case of a child with isolated late-onset epileptic spasms who significantly improved after focal frontal cortectomy. Clusters of axial and limb tonic contractions with head nodding began at 2 years of age. They occurred only during sleep, lasting 15 to 20 minutes and were pharmacoresistant. The child suffered slight mental delay. Interictal EEG showed left frontal spikes in slow sleep. Ictal video-EEG showed patterns of asymmetric spasms. MRI revealed a distinct white matter abnormality in the left frontal superior gyrus, corresponding clearly to localised cortical hypometabolism on FDG-PET and PET-MRI co-recording. SEEG investigation showed that the first spasm of the clusters corresponded to a localised discharge of rapid rhythms from the electrodes placed within the area identified as a lesion by MRI. Discharges then became more diffuse across the left frontal and temporal electrodes throughout the duration of the cluster. A tailored focal frontal resection was performed at 16 years of age. Spasms were very rare during the following three years (Engel class II). This observation illustrates the fact that isolated epileptic spasms can be cured by focal cortical resection despite a lack of clearly localised EEG surface anomalies.

FocusDET, A New Toolbox for SISCOM Analysis. Evaluation of the Registration Accuracy Using Monte Carlo Simulation

Subtraction of Ictal SPECT Co-registered to MRI (SISCOM) is an imaging technique used to localize the epileptogenic focus in patients with intractable partial epilepsy. The aim of this study was to determine the accuracy of registration algorithms involved in SISCOM analysis using FocusDET, a new user-friendly application. To this end, Monte Carlo simulation was employed to generate realistic SPECT studies. Simulated sinograms were reconstructed by using the Filtered BackProjection (FBP) algorithm and an Ordered Subsets Expectation Maximization (OSEM) reconstruction method that included compensation for all degradations. Registration errors in SPECT-SPECT and SPECT-MRI registration were evaluated by comparing the theoretical and actual transforms. Patient studies with well-localized epilepsy were also included in the registration assessment. Global registration errors including SPECT-SPECT and SPECT-MRI registration errors were less than 1.2 mm on average, exceeding the voxel size (3.32 mm) of SPECT studies in no case. Although images reconstructed using OSEM led to lower registration errors than images reconstructed with FBP, differences after using OSEM or FBP in reconstruction were less than 0.2 mm on average. This indicates that correction for degradations does not play a major role in the SISCOM process, thereby facilitating the application of the methodology in centers where OSEM is not implemented with correction of all degradations. These findings together with those obtained by clinicians from patients via MRI, interictal and ictal SPECT and video-EEG, show that FocusDET is a robust application for performing SISCOM analysis in clinical practice.

Localization Value of Magnetoencephalography Interictal Spikes in Adult Nonlesional Neocortical Epilepsy

Few studies have included magnetoencephalography (MEG) when assessing the diagnostic value of presurgical modalities in a nonlesional epilepsy population. Here, we compare single photon emission computed tomography (SPECT), positron emission tomography (PET), video-EEG (VEEG), and MEG, with intracranial EEG (iEEG) to determine the value of individual modalities to surgical decisions. We analyzed 23 adult epilepsy patients with no abnormal MRI findings who had undergone surgical resection. Localization of individual presurgical tests was determined for hemispheric and lobar locations based on visual analysis. Each localization result was compared with the ictal onset zone (IOZ) defined by using iEEG. The highest to the lowest hemispheric concordance rates were MEG (83%) > ictal VEEG (78%) > PET (70%) > ictal SPECT (57%). The highest to lowest lobar concordance rates were ictal VEEG = MEG (65%) > PET (57%) > ictal SPECT (52%). Statistical analysis showed MEG to have a higher hemispheric concordance than that of ictal SPECT (P = 0.031). We analyzed the effects of MEG clustered-area resection on surgical outcome. Patients who had resection of MEG clusters showed a better surgical outcome than those without such resection (P = 0.038). It is suggested that MEG-based localization had the highest concordance with the iEEG-defined IOZ. Furthermore, MEG cluster resection has prognostic significance in predicting surgical outcome.

Bilaterally independent epileptic spasms in a case of Aicardi syndrome

A girl with Aicardi syndrome was observed to have two distinct types of asymmetric epileptic spasms, as detected by ictal video-EEG recording at three months of age. When the two types of spasm concurred, they showed no mutual interactions based on either clinical or EEG aspects. This observation does not support the hypothesis that the brainstem always plays an initiating role in generating spasms. [Published with video sequences].

A case imitating Panayiotopoulos syndrome

Panayiotopoulos syndrome is one of the most common childhood-specific epileptic disorders. It is characterized by autonomic symptoms; the most common being emesis. However, the presence of emetic symptoms may cause misdiagnosis, for example with some organic disorders which have similar autonomic features. On the other hand, since this syndrome has been recently well documented, the tendency for early recognition may lead to overdiagnosis. Here, we present a case which could be mistaken for Panayiotopoulos syndrome based on anamnesis, however, with the aid of ictal video-EEG monitoring, the patient was shown to present with a non-epileptic psychogenic seizure. This report is an example of careful evaluation in order to avoid over- or underdiagnosis of this benign disorder. [Published with video sequences].

Benign myoclonic epilepsy in infancy followed by childhood absence epilepsy

Benign myoclonic epilepsy in infancy (BMEI) is a rare syndrome included among idiopathic generalized epilepsies (IGE) and syndromes with age-related onset. Recently, it has been shown that a few patients with BMEI later had other epilepsy types mainly IGE but never childhood absence epilepsy (CAE). We report a patient who at 11 months of age showed isolated myoclonic jerks occurring several times a day. The ictal video-EEG and polygraphic recording revealed generalized discharge of spike-wave (SW) lasting 1–2 s associated with isolated bilateral synchronous jerk involving mainly the upper limbs controlled by valproic acid (VPA). At 6 years and 8 months the child developed a new electroclinical feature recognized as CAE. The ictal EEG disclosed a burst of rhythmic 3 Hz generalized SW. Our case is the first patient with BMEI reported in the literature who later developed a CAE. This finding suggests a common neurobiological and genetic link between different age-related epileptic phenotypes.

Bilateral akinetic seizures: A clinical and electroencephalographic description

The main feature of akinetic seizures is the inhibition of voluntary movements without impairment of awareness. Most clinical information about akinetic seizures has been obtained from cortical electrical stimulation studies, whereas clinical and video-electroen-cephalography (EEG) features have not been described thoroughly. We aimed to analyze clinical and EEG characteristics of bilateral akinetic seizures (BAS). Patients with BAS were retrospectively identified from 1,858 consecutive video-EEG studies. All patients had ictal video-EEG, comprehensive clinical evaluation, neuropsychological testing, and brain magnetic resonance imaging (MRI). Ten patients (nine men) were identified; mean age was 22.5 years (range 0.3-71 years) at the time of epilepsy onset and 34.9 years (range 5-73 years) at the time of evaluation. BAS was the only seizure type in four patients. BAS consisted of sudden speech and motor arrest in eight patients, whereas in two patients seizures were characterized by abrupt freezing precipitated by gait initiation. Startle precipitated BAS in four patients. Magnetic resonance imaging (MRI) showed mesial frontal lobe lesions in six patients. Epileptiform activity was restricted to the frontal midline electrodes in all patients, with variable extension to frontal regions. In five patients, BAS were initially misdiagnosed as generalized seizures or nonepileptic events. BAS should be considered in the differential diagnosis of patients reporting paroxysmal inability to move with preservation of awareness, bearing in mind that these seizures can occur spontaneously or be precipitated by startle. The diagnosis can be achieved with video-EEG monitoring, showing stereotyped semiology and distinctive EEG abnormalities, and is often supported by the presence of lesions involving the frontal lobes.

Paroxysmal Nonkinesigenic Dyskinesia With Depression Treated by Bilateral Electroconvulsive Therapy

ranged from 10 to 20 times a day, including brief movements of the right shoulder. We diagnosed his right shoulder and upper limb movement as dyskinesia by ictal video EEG recordings. His consciousness during the seizure was maintained, and there was no postictal confusion. The precipitating factor seemed to be tense situations. Ictal EEG showed no epileptic discharge or electrodecremental pattern in all leads during the seizure. Before, during, and after the ictal period, a 9 –10 Hz background rhythm in the occipital area continued, and movement artifacts were seen. Interictal, ictal, and postictal EEG showed no other abnormality (e.g., theta or delta waves). An MRI showed no abnormality, and interictal SPECT (ECD) showed slightly lowered perfusion in the bilateral parietal area. We found no blood electrolyte imbalances or biochemical abnormalities. We tried phenytoin, clonazepam, zoni

130. Nonconvulsive status epilepticus of 17-years old girl: Case report

Objective: This case report describes a girl with epilepsy since 12 years of age, whose condition became complicated by convulsive status epilepticus at the age of 17 years. Partial complex seizures persisted even after termination of thiopental coma. The patient was treated with intravenous phenytoin. The seizures mentioned above have subsided but expressive psychic symptoms remained (visual hallucinations, déjà vu, anomic aphasia and disorientation). On the basis of ictal videoEEG with epileptiform abnormality in the left parietal localization this condition was diagnosed as a suspect NCSE of partial seizures with psychic symptomatology.

Reading epilepsy from the dominant temporo-occipital region

BackgroundReading epilepsy is a rare form of epilepsy, classified among idiopathic, age- and localisation-related (partial) epilepsies as a reflex epilepsy syndrome. Seizures usually consist of myoclonic jerks restricted to the...

SPECT periictal en la epilepsia del lóbulo temporal: valoración tras cirugía

IntroductionOur aim was to evaluate the usefulness of peri-ictal SPECT in localising the epileptogenic region (ER) in candidates for temporal lobectomy to treat medically refractory complex partial seizures (CPS). Interictal and ictal SPECT, MRI and video-EEG results were compared and the positive predictive value (PPV) was calculated in those patients with good surgical outcome. Materials and methods37 patients who had a minimum of 3 years follow-up after surgery were studied retrospectively. Pre-surgical evaluation had included video-EEG monitoring, MRI and interictal and ictal SPECT. These results were compared to the surgically treated ER and successful outcome confirmed by post-surgical clinical follow-up. 29/37 patients remained seizure-free in the post-surgical follow-up. Interictal and peri-ictal SPECT were performed using 740 MBq of 99mTc-HMPAO. Peri-ictal SPECT was ictal in 25 patients and postictal in 12. ResultsER concordance with video-EEG and peri-ictal SPECT was 86% (32/37 patients). It was 84% (31/37) for MRI and 54% (20/37 patients) for interictal SPECT. Peri-ictal SPECT localised the ER in 8/11 patients with discordant MRI and video-EEG results. Ictal SPECT localised the ER in the correct temporal lobe in 23/25 patients (92% concordance). In the 29 patients with a good surgical outcome, the PPV of video-EEG was 95% (27/29) and it was 90% (26/29) for both MRI and peri-ictal SPECT. ConclusionsPeri-ictal brain SPECT is well able to localize ER in patients with temporal lobe epilepsy. Peri-ictal SPECT concordance with ER was as good as video-EEG and MRI and its PPV was as good as that of MRI. We strongly recommend its use in the pre-surgical evaluation of temporal lobe epilepsy, especially when MRI and EEG are discordant.

Peri-ictal SPECT in temporal lobe epilepsy: post-surgical evaluation

Introduction our aim was to evaluate the usefulness of peri-ictal SPECT in localising the epileptogenic region (ER) in candidates for temporal lobectomy to treat medically refractory complex partial seizures (CPS). Interictal and ictal SPECT, MRI and video-EEG results were compared and the positive predictive value (PPV) was calculated in those patients with good surgical outcome. Materials and methods 37 patients who had a minimum of 3 years follow-up after surgery were studied retrospectively. Pre-surgical evaluation had included video-EEG monitoring, MRI and interictal and ictal SPECT. These results were compared to the surgically treated ER and successful outcome confirmed by post-surgical clinical follow-up. 29/37 patients remained seizure-free in the post-surgical follow-up. Interictal and peri-ictal SPECT were performed using 740 MBq of 99mTc-HMPAO. Peri-ictal SPECT was ictal in 25 patients and postictal in 12. Results ER concordance with video-EEG and peri-ictal SPECT was 86% (32/37 patients). It was 84% (31/37) for MRI and 54% (20/37 patients) for interictal SPECT. Peri-ictal SPECT localised the ER in 8/11 patients with discordant MRI and video-EEG results. Ictal SPECT localised the ER in the correct temporal lobe in 23/25 patients (92% concordance). In the 29 patients with a good surgical outcome, the PPV of video-EEG was 95% (27/29) and it was 90% (26/29) for both MRI and peri-ictal SPECT. Conclusions peri-ictal brain SPECT is well able to localize ER in patients with temporal lobe epilepsy. Peri-ictal SPECT concordance with ER was as good as video-EEG and MRI and its PPV was as good as that of MRI. We strongly recommend its use in the pre-surgical evaluation of temporal lobe epilepsy, especially when MRI and EEG are discordant.