A. Olivier

Epileptiform discharges in the human dysplastic neocortex: In vitro physiology and pharmacology

Field potential and intracellular recordings were made in slices of human neocortical tissue obtained during surgery for the treatment of seizures associated with focal cortical dysplasia. Ictal‐like epileptiform discharges, along with isolated field potentials, were induced by bath application of 4‐aminopyridine (50–100 μM). Some of the isolated field potentials were associated with fast transients representing population spikes. Field potential profile analysis indicated that both types of synchronous activity had maximal negative values at 1,400 to 1,600 μm from the pia. The intracellular counterpart of the ictal‐like discharge was a prolonged membrane depolarization capped by repetitive action potential burst firing. By contrast, the isolated field potentials were mirrored by long‐lasting depolarizations with minimal action potential firing; only when population spikes occurred, the isolated field potentials were associated with epileptiform action potential bursting. Ictal‐like discharges were abolished by either N‐methyl‐D‐aspartate or non–N‐methyl‐D‐aspartate receptor antagonists. In contrast, the isolated field potentials continued to occur synchronously during excitatory transmission blockade (although they lacked fast transients) but were abolished by the γ‐aminobutyric acidA receptor antagonist bicuculline methiodide (n = 2 slices). Our study demonstrates that focal cortical dysplasia tissue maintained in vitro has an intrinsic ability to generate ictal‐like epileptiform events when challenged with 4‐aminopyridine. These discharges depend on excitatory amino acid receptor–mediated mechanisms. Our results also show the presence in focal cortical dysplasia tissue of glutamatergic‐independent synchronous potentials that are mainly contributed by γ‐aminobutyric acidA receptor–mediated conductances.

Seizure-like discharges induced by lowering [Mg2+]0 in the human epileptogenic neocortex maintained in vitro

Seizure-like discharges were observed in slices of human epileptogenic neocortex maintained in vitro when [Mg2+]o was lowered near to zero. This type of epileptiform activity: (1) could occur spontaneously or following extracellular focal stimuli; (2) resembled the electrographic pattern associated with tonic-clonic seizures; (3) was accompanied by increases in [K+]o (maximally 6.2 mM from a baseline of 3.25 mM) and decreases in [Ca2+]o (maximally 0.23 mM from a baseline of 1.8 mM). Application of the selective antagonist of N-methyl-D-aspartate (NMDA) receptors, DL-2-amino-5-phosphonovalerate, suppressed in a reversible manner both spontaneous and stimulus-induced seizure-like discharges, suggesting that NMDA-activated conductances are important for the genesis of prolonged epileptiform discharges generated by human epileptogenic neocortical slices.

Occipitotemporal Epilepsies: Evaluation of Selected Patients Requiring Depth Electrodes Studies and Rationale for Surgical Approaches

Summary: In 8 patients in whom it was uncertain whether they had occipital or temporal lobe (TL) epilepsy, clinical, scalp EEG, and radiologic features were correlated with the sites of seizure onset as determined by depth EEG. The 8 patients were selected from >40 with occipital epilepsy because they had (a) an aura considered to be of occipital lobe (OL) origin, (b) an occipital interictal epileptic focus, (c) an OL lesion, or (d) a combination of all of these. Scalp EEG and clinical patterns suggested temporal involvement in all, however. Extracranial EEG recordings were often misleading, showing multilobar interictal epileptic abnormalities, and seizure onset was of poor localizing value and did not clarify the problem sufficiently. Intracranial EEG recordings showed that seizure onset could be ordered along an Occipitotemporal gradient. Consistent OL seizure onset was observed in patients who had only elementary visual auras. Those who had inconsistent aura or no aura, suggesting OL origin, had onset of most attacks in the TL. All patients had a seizure spread pattern suggesting early TL involvement. To prevent visual field defect, surgical approaches included temporal resection when temporal seizure origin or spread was demonstrated; although occasionally this produced excellent results, it was of limited benefit in most patients, even when some seizures were proven to originate in TL structures. In patients with malignant epilepsy and in those with an occipital lesion, occipital resection should be considered.

Acute Postictal Psychosis: A Stereo EEG Study

Summary An acute psychosis characterized by auditory hallucinations and paranoid delusions developed in a 19‐year‐old man with temporal lobe epilepsy after he had a cluster of seizures when antiepileptic drugs (AEDs) had been gradually discontinued. Continuous stereotactic depth and epidural EEG recordings confirmed that this was a postictal rather than an ictal event. Acute postictal psychosis is a self‐limited condition phenomenologically distinct from ictal or postictal confusion.

Electrocorticography and outcome in frontal lobe epilepsy

The prognostic significance of epileptiform activity (EA) recorded at electrocorticography (ECOG) was examined in a group of 60 consecutive non-tumoral patients with intractable frontal lobe epilepsy (FLE). Pre-excision EA was documented as absent, focal (one gyrus), regional (two gyri), lobar (3 gyri) or multilobar (frontal + temporal gyri). Post-excision EA was documented as absent, restricted to the resection border, or recorded distant to the resection border, and was quantitated by spike frequency. Pre-excision EA from < or = 2 gyri and absence of post-resection EA correlated with Class I or II (Engel classification) outcome while pre-excision EA from > or = 3 gyri and persistent post-resection EA, especially distant to the resection border, correlated with Class III or IV outcome (P < 0.001). A significant correlation between poorer outcomes and increased abundance of distant post-resection EA was observed (P < 0.001). EA restricted to the resection border was not significantly correlated with outcome. Presence of a circumscribed lesion correlated with Class I outcome (P < 0.01) and absence of pathological abnormality correlated with Class IV outcome (P < 0.05). Neither side nor extent of surgical excision correlated with outcome. EA recorded at ECOG is of prognostic significance in FLE. A lobar or multilobar distribution of pre-excision EA and persistent post-excision EA distant to the resection border, especially when abundant, are highly unfavorable prognostic indicators. In contrast, a restricted distribution of pre-excision EA and absence of post-resection EA both herald a favorable outcome.

Reevaluation of surgical failures and the role of reoperation in 39 patients with frontal lobe epilepsy.

Summary: Between 1929 and 1980, 284 patients with refractory nontumoral frontal lobe epilepsy (FLE) underwent operation at the Montreal Neurological Institute (MNI). We studied 39 patients (14%) who required reoperation. Mean age at the time of first operation was 18 years and at reoperation was 22 years. Clinical manifestations were similar to those of patients with “a pure culture of frontal lobe epilepsy” as reported by Rasmussen in 1983. At the time of first operation, large epileptogenic zones were noted in most patients. Resection was confined to the frontal lobe. Continuing seizure activity was due to residual areas of epileptogenesis, and reoperation with more extensive resection of cortex increased the number of seizure‐free patients. Twenty‐six patients underwent further frontal resection, and in 13 surgical removal was extended to the temporal lobe. Residual electrocorticographic (ECoG) spiking was documented in 15 of 23 (65%) of the reoperated patients. Thirty‐five patients were followed for periods ranging from 4 to 46 years. One fifth became seizure‐free, and 31% had significant seizure reduction. Thus, half of these patients had a good result. Patients with residual postexcision ECoG spiking had poor outcomes and evidence of large epileptogenic zones. None of the patients who underwent frontotemporal resections became seizure‐free. Reoperation should be considered if initial resection does not lead to a satisfactory result and may convert an initial failure into a good surgical result.

Increased neocortical spiking and surgical outcome after selective amygdalo-hippocampectomy

Abstract We studied the electrocorticogram (ECoG) before and immediately after transcortical selective amygdalo-hippocampectomy, prospectively in 13 consecutive patients and retrospectively in three others. ECoG was performed with surface and two depth electrodes inserted through T2 aimed at the amygdala and anterior hippocampus. Before resection the ECoG showed a variable amount of interictal spiking, recorded either independently from the depth and surface, or synchronously. A small cortical incision (2–3 cm) was made in T2. The hippocampus, amygdala and parahippocampal gyrus were removed subpially. After the resection, increased epileptiform abnormality was observed in all 16 patients and a different ECoG pattern emerged. It consisted of repetitive, high amplitude spikes and polyspikes, separated by attenuated background, recorded from the most anterior temporal area. Similar observations were reported by Niemeyer in 1958. The outcome was comparable to that of standard anterior temporal resection: 62.5% class I and 25% class II (Engels scale). ECoG is often used to tailor the amount of resection, and the persistence of epileptic abnormalities correlates with worse outcome. This is not the case in selective amygdalo-hippocampectomy, suggesting that a different underlying mechanism is responsible for the increased interictal spiking following this procedure.

Morbidity of chronic recording with intracranial depth electrodes in 170 patients.

A consecutive series of 170 patients who have been submitted to intracranial depth electrode recordings is reviewed to assess the overall morbidity of the technique. Most patients had bitemporal and frontal electrodes inserted and were monitored for an average period of 18 days. A surgically amenable focus was found in 85% of the cases. There were 4 cases of infection including 2 cerebral abscesses which required surgical evacuation. One patient with frontal lobe atrophy developed an acute subdural hematoma after electrode implantation. There was no death or neurological deficit in the entire series. Morbidity was encountered mainly in the neuropsychological sphere, several patients having developed transient postictal psychosis after repetitive seizures. Our recording technique has been associated with low surgical morbidity. Patients undergoing depth electrode recordings should be closely monitored to minimize the occurrence of psychotic episodes associated with drug withdrawal and increased seizure frequency.

Induction of burst-suppression and activation of epileptiform activity after methohexital and selective amygdalo-hippocampectomy

Electrocorticography (ECOG) compared the effects of methohexital (MTH) and selective amygdalo-hippocampectomy (selAH) upon lateral temporal neocortical epileptiform activity (EA) in 31 patients with mesial temporal epilepsy. Pre-excision ECOG showed independent neocortical EA before MTH in 12/31 and after MTH in 18/31. MTH (20-50 mg) activated neocortical EA in 12 cases and induced burst-suppression (BS) over temporal neocortex in 14/31. Post-excision ECOG showed neocortical EA in 21/31 and BS in 27/31: compared with pre-excision ECOG before MTH, selAH activated neocortical EA in 15 cases. Significant correlations were found between presence of pre-excisional neocortical EA and presence of post-excisional neocortical EA (P < 0.001) and between activation of pre-excisional neocortical EA by MTH and activation of (post-excisional) neocortical EA by selAH (P < 0.006). Presence or severity of BS in the post-excision ECOG was not correlated with presence, absence or activation of post-excisional EA. Presence of neocortical EA was significantly correlated with a higher pre-operative seizure frequency (P < 0.001) but not with duration of epilepsy nor surgical outcome. Both MTH and selAH can induce neocortical BS, likely through chemical and surgical disconnection of cortex, respectively. Unrelated to induction of BS, MTH and selAH appear to decrease threshold for expression of neocortical EA in a similar fashion.

Excitatory Amino Acids Modulate Phosphoinositide Signal Transduction in Human Epileptic Neocortex

Summary: Stimulation of phosphoinositide (PI) hydrolysis by norepinephrine (NE), carbachol (Carb), and excitatory amino acids (EAAs) was measured in slices prepared from neocortex excised during epilepsy surgery. NE and Carb markedly enhanced PI turnover (EC50: NE, 12 μM; Carb, 661 μM) as reflected by [3H]inositol monophosphate (IP1) accumulation in tissue slices prelabeled with [3H]myoinositol. These effects were dose‐dependent, saturable, and five to six times higher than basal IP1 accumulation. A weaker stimulation (twofold) was observed with quisqualate (QUIS; EC50, 1.1 μM) and glutamate (GLU; EC50, >1 mM), while minimal or no stimulation was seen with kainate (KA) and N‐methyl‐D‐aspartate (NMDA). Agonist‐stimulated PI turnover was significantly reduced in samples from actively spiking epileptic neocortex versus nonspiking areas as defined by electrocorticography (NE, ‐23%, p < 0.05; Carb, ‐44%, p < 0.01). Preincubation of slices with various EEAs inhibited Carb‐induced IP1 formation. The maximal extent of inhibition (1 mM) was both amino acid‐(NMDA > KA > QUIS > GLU) and concentration‐dependent (IC50: NMDA, 5 μM; KA, 3.3 μM; QUIS, 47 μM; GLU, > 1 mM). These data suggest that epileptic activity modulates PI metabolism and alters receptor‐effector coupling. As important mediators of epileptogenesis, EAAs may interfere with the efficiency of this second messenger system.