Persistent Epileptiform Discharges Research Articles

Visual Diagnosis: Abnormal Behavior in a 2-month-old Boy.

Visual Diagnosis: Abnormal Behavior in a 2-month-old Boy.

Mild malformation of cortical development with oligodendroglial hyperplasia and epilepsy (MOGHE): a widespread disease with an apparently focal epilepsy.

Mild malformation of cortical development with oligodendroglial hyperplasia and epilepsy (MOGHE) is a recently recognized, highly epileptogenic, distinct histopathological entity in drug-resistant epilepsy that primarily involves the frontal lobes. Surgical outcomes in MOGHE are variable. Although the diagnosis is based on histopathology, high-resolution MRI helps to differentiate MOGHE preoperatively from other forms of cortical malformations (i.e., mMCD II and FCD IIa). We discuss the clinical, electrographic, radiological and histopathological characteristics of MOGHE in two patients who underwent evaluation for drug-resistant epilepsy followed by electrocorticography-based resection. Both patients presented with childhood-onset refractory frontal lobe epilepsy with a high seizure burden. Interictal epileptiform discharges were widespread. PET abnormalities were disproportionate to the MRI findings. Cognitive impairment, persistent epileptiform discharges on post-resection electrocorticography and sub-optimal surgical outcomes suggest that MOGHE is a widespread pathology in focal epilepsy.

Endogenous adenosine induces NMDA receptor-independent persistent epileptiform discharges in dorsal and ventral hippocampus via activation of A2 receptors

Although adenosine is widely assumed to be an endogenous anticonvulsant its role in epileptogenesis is still contradictory. Using slices from the dorsal (DH) and the vental (VH) rat hippocampus and extracellular recordings from the CA3 field we aimed to determine the effects of endogenous adenosine on the expression and long-term maintenance of epileptiform activity induced by blockade of adenosine receptors types A(1) (A(1)R) and A(2) (A(2)R) under conditions of low magnesium. We found that the A(1)Rs blockade induced persistent epileptiform discharges (PED) more frequently in VH (by 52%) than in DH (by 31%). The induction of PED upon an additional blockade of A(2)Rs increased in VH (by 48%) but decreased in DH (by 74%). Remarkably, the increment in VH was prevented by a blockade of NMDARs. A blockade of A(2)Rs increased the NMDAR-mediated component of evoked synaptic potential in both VH and DH (by ~100%) but suppressed the non-NMDAR-mediated component in DH but not VH. A blockade of A(1)Rs induced PED equally in DH (76%) and VH (80%) via a NMDAR-independent mechanism. A blockade of A(2)Rs under blockade of A(1)Rs and NMDARs reduced the PED to 17% in DH and to 38% in VH. These findings show that A(2)Rs play a different role in the long-term maintenance of epileptiform activity between DH and VH and suggest that endogenous activation of A(2)Rs facilitates NMDAR-independent induction of PED in both hippocampal poles, but suppresses NMDAR-dependent induction of PED in VH.

The Mozart Effect & Epilepsy

The Mozart Effect & Epilepsy

The long-term effect of listening to Mozart K.448 decreases epileptiform discharges in children with epilepsy

Mozart's Sonata for Two Pianos in D major, K.448 (Mozart K.448), has been shown to improve mental function, leading to what is known as the Mozart Effect. Our previous work revealed that epileptiform discharges in children with epilepsy decrease during and right after listening to Mozart K.448. However, the duration of the effect was not studied. In the study described here, we evaluated the long-term effect of Mozart K.448 on epileptiform discharges in children with epilepsy. Eighteen children with epilepsy whose seizures were clinically well controlled with antiepileptic drugs were included. For each child, EEGs had revealed persistent epileptiform discharges for at least 6months. These patients listened to Mozart K.448 for 8minutes once a day before bedtime for 6months. Epileptiform discharges were recorded and compared before and after 1, 2, and 6months of listening to Mozart K.448. All of the children remained on the same antiepileptic drug over the 6months. Relationships between number of epileptiform discharges and foci of discharges, intelligence, epilepsy etiology, age, and gender were analyzed. Epileptiform discharges significantly decreased by 53.2±47.4, 64.4±47.1, and 71.6±45.8%, respectively, after listening to Mozart K.448 for 1, 2, and 6 months. All patients except those with occipital discharges showed a significant decrease in epileptiform discharges. Patients with normal intelligence and idiopathic epilepsy had greater decreases than those with mental retardation and symptomatic epilepsy. Age and gender did not affect the results. We conclude that long-term listening to Mozart K.448 may be effective in decreasing epileptiform discharges in children with epilepsy in a chronologically progressive manner.

F-MRI in Epilepsy with Spike and Wave Activity Evoked by Eye Closure: Different Bold Activation in a Patient with Idiopathic Partial Epilepsy with Occipital Spikes and a Control Group

We performed functional magnetic resonance imaging (fMRI) in a 30-year-old man with idiopathic partial epilepsy with occipital spikes whose scalp EEG activity was characterized by persistent epileptiform discharges on eye closure, ceasing upon eye opening. We compared BOLD activation in the patient and in a control group of three normal volunteers. f-MRI showed that occipital cortex and frontal areas were activated in relation to eye movement in normal subjects during eye opening but not during eye closing. While persistent interictal spike and wave activity was present over the posterior and anterior scalp in the patient upon eye closing, f-MRI showed bilateral activation of the parietal and temporal regions. This fMRI study documents the activation of posterior and temporal areas related to continuous intercritical spikes evoked by eye closure, which are diffuse over the scalp. This activation was absent in the control group during eye closure.

Homeostatically regulated spontaneous neuronal discharges protect developing cerebral cortex networks from becoming hyperactive following prolonged blockade of excitatory synaptic receptors

In order to further examine the role of spontaneous action potential (SAP) discharges in neocortical development, amino-acid-mediated synaptic transmission was selectively blocked in an improved organotypic neocortex culture preparation. Contralateral occipital cortex slices from neonatal rats were co-cultured for several weeks in a ventricle-to-ventricle orientation known to greatly enhance cyto-morphological and electrophysiological maturation. Such preparations are highly resistant to attempts to suppress neuronal firing by blocking ionotropic glutamate receptors: not only can kainate receptors partly substitute for NMDA- and AMPA-mediated neurotransmission when these receptors are pharmacologically blocked, but (muscarinic) cholinergic receptors also begin to drive SAP activity when the kainate receptors, too, are chronically blocked. Only tetrodotoxin proved able to eliminate SAPs altogether in these co-cultures, while GABAergic receptor blockade (using bicucculine) led to persistent epileptiform discharges. Treatment effects were assayed upon transfer to control medium by means of a quantitative analysis of spontaneously occurring polyneuronal spike trains. Total suppression of action potentials for several weeks (by tetrodotoxin treatment) led, as in earlier experiments, to strongly intensified burst firing upon transfer to control medium. Chronic glutamate receptor blocked cultures, on the other hand, showed only minor deviations from control firing levels and patterns when assayed in normal medium. Protection against the development of hyperactivity despite partial blockade of synaptic transmission was roughly proportional to the degree to which spontaneous firing during the treatment period approximated normal SAP levels. This homeostatic response to chronically reduced excitatory drive thus differs from earlier results using isolated organotypic cortex cultures, in which the restoration of SAP activity failed to prevent the development of network hyperactivity. Chronic bicucculine treatment, in contrast, had little or no homeostatic effect on SAP firing patterns; on the contrary, opposite to earlier findings using isolated occipital cortex explants, paroxysmal discharges persisted even after transfer to control medium.

Greater contribution of N-methyl- d-aspartic acid receptors in ventral compared to dorsal hippocampal slices in the expression and long-term maintenance of epileptiform activity

Functional segregation along the dorso-ventral axis of the hippocampus is a developing concept. The higher susceptibility of the ventral hippocampus to epileptic activity compared with dorsal hippocampus is one of the main features, which still has obscure mechanisms. Using the model of magnesium-free medium and field recordings, single epileptiform discharges displayed higher incidence (77% vs 57%), rate (41.7±3.1 vs 13.5±0.7 events/min), duration (173.9±17.7 vs 116.8±13.6ms) and intensity (coastline, 25.4±2.5 vs 9.5±1.8) in ventral compared with dorsal rat hippocampal slices. In addition, the decay phase of the evoked synaptic potentials was 110% slower in ventral slices. The N-methyl- d-aspartate (NMDA) receptor antagonist d-(−)-2-amino-5-phosphonopentanoic acid (50–100μM) decreased the discharge rate and coastline similarly in ventral and dorsal slices, but it shortened the discharges in ventral slices (by 40%) only. The NMDA receptor antagonist 3-(( R)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (10μM) decreased the rate in both groups and additionally shortened discharges in both kinds of slices, an effect which was greater in ventral ones (31% vs 13%). Furthermore, both drugs shortened the evoked potentials more in ventral (77%) than in dorsal slices (52%). On the other hand, 1μM of 3-(( R)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid shortened the discharges and evoked synaptic potentials only in ventral slices, and slowed down the discharge rate only in dorsal slices. Addition of NMDA, in the magnesium-free medium, enhanced activity in both kinds of slices. At 5 and 10μM of NMDA 51% of the ventral but only 9% of the dorsal slices displayed persistent epileptiform discharges, which were recorded for at least one hour after reintroduction of magnesium in the medium. At 10–20μM the enhancement of activity was transient, followed by suppression of discharges in 40% and 76% of the ventral and dorsal slices, respectively. Most of the slices having experienced suppression did not develop persistent activity. We propose that the NMDA receptors contribute to the higher susceptibility of the ventral hippocampus to expression and long-term maintenance of epileptiform discharges. This diversification may be related to other aspects of hippocampal dorso-ventral functional segregation.

Acute desensitization of presynaptic GABAB-mediated inhibition and induction of epileptiform discharges in the neonatal rat hippocampus.

The consequences of sustained activation of GABA(B) receptors on GABA(B)-mediated inhibition and network activity were investigated in the neonatal rat hippocampus using whole-cell and extracellular field recordings. GABA(B)-mediated presynaptic control of gamma-aminobutyric acid (GABA) release progressively diminished with time in spite of the continued presence of the agonist (100 microM baclofen, 15 min), indicating acute desensitization of presynaptic GABA(B)-mediated inhibition on GABAergic terminals. By contrast, neither GABA(B)-mediated inhibition of glutamate release nor postsynaptic GABA(B)-mediated inhibition seemed to produce this desensitization. Efficacy of presynaptic GABA(B) receptors was still reduced by 49% 30 min after baclofen washout, suggesting a long timeframe for recovery from desensitization. The 15-min baclofen application was followed by a dramatic modification of the spontaneous network activity, with the occurrence of epileptiform events called ictal-like discharges (ILDs). Extracellular field recordings confirmed the epileptic nature of the discharges that could be recorded up to 4 h after baclofen washout. ILDs did not occur when the GABA(B) receptor antagonist CGP35348 was coapplied with baclofen. This indicates that ILD induction is a consequence of the sustained activation of GABA(B) receptors and the correlated changes in GABA(B)-mediated inhibition. Furthermore, ILDs were also induced when blocking with CGP35348 an amount of GABA(B) receptors that exactly mimicked the loss of inhibition obtained with desensitization. These results show that presynaptic GABA(B)-mediated inhibition of GABA release acutely and specifically desensitizes following a sustained application of the GABA(B) receptor agonist baclofen. Conditions that induce desensitization of the GABA(B)-mediated responses also trigger persistent epileptiform discharges in the neonatal rat hippocampus.

Prolonged epileptic blindness in an infant associated with cortical dysplasia

We report a female infant with status epilepticus amauroticus and intractable focal motor seizures associated with congenital cortical dysplasia. EEG demonstrated persistent epileptiform discharges over the right parieto‐temporal regions extending to occipital areas. She required cortical resection of the epileptic zone at age 8 months given failure of very high dose antiepileptic combinations. Histological analysis of a sample of cortex resected from the right central parieto‐temporal region, identified by electrocorticography as the focus of epileptic activity, showed cortical dysplasia. The seizures ceased and the infant gained full vision after 48 hours. During an 8‐year follow‐up period she has had a few short‐lived seizures, currently controlled with carbamazepine and vigabatrin. Her cognition and speech are intact. This case demonstrates that: (1) resection of a central temporo‐parietal focus, which may have spread to the occipital regions, may result in complete visual recovery and cessation of seizures; and (2) EEG should be considered in every infant with alleged delayed visual maturation, to rule out concealed epileptic activity.