scholarly journals Specific imbalance of excitatory/inhibitory signaling establishes seizure onset pattern in temporal lobe epilepsy

2016 ◽  
Vol 115 (6) ◽  
pp. 3229-3237 ◽  
Author(s):  
Massimo Avoli ◽  
Marco de Curtis ◽  
Vadym Gnatkovsky ◽  
Jean Gotman ◽  
Rüdiger Köhling ◽  
...  

Low-voltage fast (LVF) and hypersynchronous (HYP) patterns are the seizure-onset patterns most frequently observed in intracranial EEG recordings from mesial temporal lobe epilepsy (MTLE) patients. Both patterns also occur in models of MTLE in vivo and in vitro, and these studies have highlighted the predominant involvement of distinct neuronal network/neurotransmitter receptor signaling in each of them. First, LVF-onset seizures in epileptic rodents can originate from several limbic structures, frequently spread, and are associated with high-frequency oscillations in the ripple band (80–200 Hz), whereas HYP onset seizures initiate in the hippocampus and tend to remain focal with predominant fast ripples (250–500 Hz). Second, in vitro intracellular recordings from principal cells in limbic areas indicate that pharmacologically induced seizure-like discharges with LVF onset are initiated by a synchronous inhibitory event or by a hyperpolarizing inhibitory postsynaptic potential barrage; in contrast, HYP onset is associated with a progressive impairment of inhibition and concomitant unrestrained enhancement of excitation. Finally, in vitro optogenetic experiments show that, under comparable experimental conditions (i.e., 4-aminopyridine application), the initiation of LVF- or HYP-onset seizures depends on the preponderant involvement of interneuronal or principal cell networks, respectively. Overall, these data may provide insight to delineate better therapeutic targets in the treatment of patients presenting with MTLE and, perhaps, with other epileptic disorders as well.

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Haiyu Liu ◽  
Uilki Tufa ◽  
Anya Zahra ◽  
Jonathan Chow ◽  
Nila Sivanenthiran ◽  
...  

Abstract Epilepsy is a chronic neurological disorder characterized by spontaneous recurrent seizures (SRS) and comorbidities. Kindling through repetitive brief stimulation of a limbic structure is a commonly used model of temporal lobe epilepsy. Particularly, extended kindling over a period up to a few months can induce SRS, which may simulate slowly evolving epileptogenesis of temporal lobe epilepsy. Currently, electroencephalographic (EEG) features of SRS in rodent models of extended kindling remain to be detailed. We explored this using a mouse model of extended hippocampal kindling. Intracranial EEG recordings were made from the kindled hippocampus and unstimulated hippocampal, neocortical, piriform, entorhinal, or thalamic area in individual mice. Spontaneous EEG discharges with concurrent low-voltage fast onsets were observed from the two corresponding areas in nearly all SRS detected, irrespective of associated motor seizures. Examined in brain slices, epileptiform discharges were induced by alkaline artificial cerebrospinal fluid in the hippocampal CA3, piriform and entorhinal cortical areas of extended kindled mice but not control mice. Together, these in vivo and in vitro observations suggest that the epileptic activity involving a macroscopic network may generate concurrent discharges in forebrain areas and initiate SRS in hippocampally kindled mice.


Author(s):  
Mohammed M. Jan ◽  
Mark Sadler ◽  
Susan R. Rahey

Electroencephalography (EEG) is an important tool for diagnosing, lateralizing and localizing temporal lobe seizures. In this paper, we review the EEG characteristics of temporal lobe epilepsy (TLE). Several “non-standard” electrodes may be needed to further evaluate the EEG localization, Ictal EEG recording is a major component of preoperative protocols for surgical consideration. Various ictal rhythms have been described including background attenuation, start-stop-start phenomenon, irregular 2-5 Hz lateralized activity, and 5-10 Hz sinusoidal waves or repetitive epileptiform discharges. The postictal EEG can also provide valuable lateralizing information. Postictal delta can be lateralized in 60% of patients with TLE and is concordant with the side of seizure onset in most patients. When patients are being considered for resective surgery, invasive EEG recordings may be needed. Accurate localization of the seizure onset in these patients is required for successful surgical management.


2006 ◽  
Vol 105 (1) ◽  
pp. 77-87 ◽  
Author(s):  
Frederic Collignon ◽  
Nicholas M. Wetjen ◽  
Aaron A. Cohen-Gadol ◽  
Gregory D. Cascino ◽  
Joseph Parisi ◽  
...  

Object The causes of epileptic events remain unclear. Much in vitro and in vivo experimental evidence suggests that gap junctions formed by connexins (Cxs) between neurons and/or astrocytes contribute to the generation and maintenance of seizures; however, few experiments have been conducted in humans, and those completed have shown controversial data. The authors designed a study to compare the level of expression of Cxs in hippocampi from epileptic and nonepileptic patients to assess whether an alteration of gap junction expression in epileptic tissue plays a role in seizure origin and propagation. Methods The expression of Cxs32, -36, and -43 was studied in 47 consecutive samples of hippocampi obtained from epileptic patients who had undergone an amygdalohippocampectomy for the treatment of intractable seizure. These expression levels were compared with those in hippocampi obtained in nonepileptic patients during postmortem dissection. Immunostaining was performed to create one slide for each of the three Cxs. Each slide demonstrated multiple cells from each of six regions (CA1, CA2, CA3, CA4, dentate gyrus, and subiculum). Two independent reviewers rated each Cx–region combination according to an immunoreactive score. Across all three measures—that is, staining intensity, percentage of positively stained cells, and immunoreactive score—Cx32 appeared to be expressed at a significantly lower level in the epileptic patients compared with controls (p < 0.001 for each measure), whereas Cx43 appeared to be expressed more among the epileptic patients (p < 0.001 for each measure). There was no evidence of any differential expression of Cx36. There was, however, regional variation within each Cx subtype. For Cx36, the staining intensity was higher in the CA2 region in the epilepsy group. Conclusions The increase in Cx43, decrease in Cx32, and preservation of Cx36 expression in hippocampi from epileptic persons could play a role in the development of seizures in patients with temporal sclerosis. Additional studies must be completed to understand this mechanism better.


Epilepsia ◽  
2000 ◽  
Vol 41 (11) ◽  
pp. 1411-1419 ◽  
Author(s):  
Takeharu Kunieda ◽  
Akio Ikeda ◽  
Nobuhiro Mikuni ◽  
Shinji Ohara ◽  
Akiyo Sadato ◽  
...  

2002 ◽  
Vol 87 (1) ◽  
pp. 634-639 ◽  
Author(s):  
Margherita D'Antuono ◽  
Ruba Benini ◽  
Giuseppe Biagini ◽  
Giovanna D'Arcangelo ◽  
Michaela Barbarosie ◽  
...  

In mouse brain slices that contain reciprocally connected hippocampus and entorhinal cortex (EC) networks, CA3 outputs control the EC propensity to generate experimentally induced ictal-like discharges resembling electrographic seizures. Neuronal damage in limbic areas, such as CA3 and dentate hilus, occurs in patients with temporal lobe epilepsy and in animal models (e.g., pilocarpine- or kainate-treated rodents) mimicking this epileptic disorder. Hence, hippocampal damage in epileptic mice may lead to decreased CA3 output function that in turn would allow EC networks to generate ictal-like events. Here we tested this hypothesis and found that CA3-driven interictal discharges induced by 4-aminopyridine (4AP, 50 μM) in hippocampus-EC slices from mice injected with pilocarpine 13–22 days earlier have a lower frequency than in age-matched control slices. Moreover, EC-driven ictal-like discharges in pilocarpine-treated slices occur throughout the experiment (≤6 h) and spread to the CA1/subicular area via the temporoammonic path; in contrast, they disappear in control slices within 2 h of 4AP application and propagate via the trisynaptic hippocampal circuit. Thus, different network interactions within the hippocampus-EC loop characterize control and pilocarpine-treated slices maintained in vitro. We propose that these functional changes, which are presumably caused by seizure-induced cell damage, lead to seizures in vivo. This process is facilitated by a decreased control of EC excitability by hippocampal outputs and possibly sustained by the reverberant activity between EC and CA1/subiculum networks that are excited via the temporoammonic path.


Neurology ◽  
2001 ◽  
Vol 57 (7) ◽  
pp. 1184-1190 ◽  
Author(s):  
R. C. Knowlton ◽  
K. D. Laxer ◽  
G. Klein ◽  
S. Sawrie ◽  
G. Ende ◽  
...  

Epilepsia ◽  
2006 ◽  
Vol 47 (8) ◽  
pp. 1300-1307 ◽  
Author(s):  
Tonicarlo R. Velasco ◽  
Americo C. Sakamoto ◽  
Veriano Alexandre ◽  
Roger Walz ◽  
Charles L. Dalmagro ◽  
...  

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