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Biomedical subjects

J Engel

Publications and source records attributed to J Engel.

At least 181 records · Page 10Linked to original sources

Olfactory bedside test. A simple approach to identify temporo-orbitofrontal dysfunction.

BACKGROUND: Olfactory memory and discrimination are processed by the anteromesial temporal cortex and the orbitofrontal cortex. Both functions may therefore be impaired in limbic epilepsy. METHODS: Twenty-seven patients with mesial temporal lobe seizures (MTLS), 10 patients with neocortical seizures (NS), and 10 matched healthy control subjects underwent evaluation for olfactory quality discrimination (OD) and delayed recognition memory (OM). All patients were referred for presurgical evaluation. The olfactory tests were performed in a same-different paradigm with 10 seconds (OD) and 60 minutes (OM) between presentations of the odors, using the standardized University of Pennsylvania Smell Identification Test. The presentations were monorhinal in the OD and birhinal in the OM tests. The results were related to regional glucose metabolism measured with fludeoxyglucose F 18 positron emission tomography. RESULTS: Patients with MTLS had an impaired OD ipsilateral to the epileptogenic region (P < .001) and a higher total number of errors (including both tests) (P = .002). They also had lower OM scores, but not significantly lower than those of patients with NS (P = .05). The combined OM and OD tests correctly identified patients with MTLS with a sensitivity of 85% and a specificity of 90%, offering a correct lateralization in 74% of patients. Patients with MTLS whose OD was more impaired than OM differed from those with more impaired OM by having a significant hypometabolism not only over the neocortex of the epileptogenic temporal lobe (P = .02) but also in the ipsilateral anterior (P = .008) and orbitofrontal cortex (P = .007) (2-way analysis of variance). CONCLUSIONS: Tests of olfactory function are useful in distinguishing between NS and MTLS. The impairments of OM and OD can be dissociated in pathological states and therefore mediated by different structures.

Adult↗

Local resection and brachytherapy confined to the lumpectomy site for early breast cancer: a pilot study.

BACKGROUND AND OBJECTIVES: The commonest site of local breast recurrence after breast conservation surgery is the primary tumor bed. We have tested the feasibility of outpatient high dose rate brachytherapy to the primary tumor bed as the only radiation. Our technique relies on the placement of surgical clips to mark the tumor bed. METHODS: Between March 1992 and January 1996, 39 patients with clinical T1 T2 breast cancer were enrolled in this pilot study. The first 13 patients had intraoperative implantation of the breast. The remaining 26 patients had outpatient postoperative implantation under general anesthesia (2 patients) or local anaesthesia (24 patients). High dose rate brachytherapy was given twice daily at least 6 hours apart for a total dose of 37.2 Gy in 10 fractions over 5-7 days. RESULTS: Three patients had mild clinical cellulitis responding to oral antibiotics. One patient had a small sinus in the lumpectomy scar requiring local excision to heal. Four patients developed fat necrosis at the lumpectomy site at 4 (1 patient), 13 (1 patient), and 18 months (2 patients) post radiotherapy. Patient rated satisfaction with treatment was high. At a median followup of 20 months, one infield local recurrence has been salvaged by wider resection and postoperative conventional external beam radiation. CONCLUSIONS: Except for fat necrosis, which may be associated with this technique, complications have been minimal. Outpatient implantation under local anesthesia is feasible. Longer followup is required to establish the local control rates.

Adult↗

Heteronuclear NMR assignments and secondary structure of the coiled coil trimerization domain from cartilage matrix protein in oxidized and reduced forms.

The C-terminal oligomerization domain of chicken cartilage matrix protein is a trimeric coiled coil comprised of three identical 43-residue chains. NMR spectra of the protein show equivalent magnetic environments for each monomer, indicating a parallel coiled coil structure with complete threefold symmetry. Sequence-specific assignments for 1H-, 15N-, and 13C-NMR resonances have been obtained from 2D 1H NOESY and TOCSY spectra, and from 3D HNCA, 15N NOESY-HSQC, and HCCH-TOCSY spectra. A stretch of alpha-helix encompassing five heptad repeats (35 residues) has been identified from intra-chain HN-HN and HN-H alpha NOE connectivities. 3JHNH alpha coupling constants, and chemical shift indices. The alpha-helix begins immediately downstream of inter-chain disulfide bonds between residues Cys 5 and Cys 7, and extends to near the C-terminus of the molecule. The threefold symmetry of the molecule is maintained when the inter-chain disulfide bonds that flank the N-terminus of the coiled coil are reduced. Residues Ile 21 through Glu 36 show conserved chemical shifts and NOE connectivities, as well as strong protection from solvent exchange in the oxidized and reduced forms of the protein. By contrast, residues Ile 10 through Val 17 show pronounced chemical shift differences between the oxidized and reduced protein. Strong chemical exchange NOEs between HN resonances and water indicate solvent exchange on time scales faster than 10 s, and suggests a dynamic fraying of the N-terminus of the coiled coil upon reduction of the disulfide bonds. Possible roles for the disulfide crosslinks of the oligomerization domain in the function of cartilage matrix protein are proposed.

Amino Acid Sequence↗

The development of alkylphosphocholines as signal transduction inhibitors: experimental and clinical challenges.

Alkylphosphocholines are a new class of anticancer agents. Their mode of action is considered to be related to the inhibition of phospholipase C and protein kinase C. These enzymes play a major role in intracellular signalling pathways. Their inhibition by alkylphosphocholines leads in the dimethylbenzanthracene-induced mammary carcinoma of the rat to a response pattern similar to that of the antiestrogen zindoxifene. This suggests that the inhibition of transcription factor formation might be the common pathway for alkylphosphocholines and antihormones. Based on the experimental dose-response pattern, new clinical strategies for dose finding and response evaluation will have to be developed for inhibitors of signal transduction, such as alkylphosphocholines.

Animals↗

[The effect of needle type and immobilization on postspinal headache].

UNLABELLED: Post-dural puncture headache (PDPH) is a significant complication of spinal anaesthesia. Diameter and tip of the needle as well as the patient's age have been proven to be important determinants. The question of whether post-operative recumbency can reduce the risk of PDPH has not been answered uniformly. And besides, some studies referring to this subject reveal methodical failures, for example, as to clear definition and exact documentation of post-operative immobilization. Furthermore, fine-gauge needles (26G or more) have not been investigated yet. The first aim of our study was therefore to examine the role of recumbency in the prevention of PDPH under controlled conditions using thin needles. Secondly, we wanted to confirm the reported prophylactic effect of needles with a modified, atraumatic tip (Whitacre and Atraucan) by comparing them to Quincke needles of identical diameter. Most of the former investigators compared Quincke with atraumatic needles of different size regardless of the known influence of the diameter on PDPH. PATIENTS AND METHODS: In a prospective study we included 481 consecutive patients undergoing a total of 500 orthopaedic operations under spinal anaesthesia. The latter was performed in a standardized manner (patient sitting, midline approach, needle with parallel bevel direction), using four different needles allocated randomly (26-gauge and 27-gauge needles with Quincke tip, 26-gauge Atraucan and 27-gauge Whitacre cannula). Half of the patients were instructed to stay in bed for 24 h (horizontal position without raising head), the others to get up as early as possible. An anaesthesiologist visited the patients on the fourth postoperative day or later and questioned them about headache and duration of recumbency. Additionally, the patients had to fill out a questionnaire 1 week after surgery. Any postural headache was considered as PDPH. RESULTS: The four groups of different needles had homogeneous demographic characteristics (see Table 1). A total of 47 patients (9.4%) developed PDPH. The incidence was highest after puncture with a 26-gauge Quincke cannula (17.6%) with a significant difference compared to the other needles (see Table 2). PDPH incidence correlated well with increasing age and number of dural punctures, but showed no relation to sex, patient's history of headache or experience of the anaesthesiologist. Only about half of the patients (60.5%) followed the instructions regarding mobilization or recumbency. The duration of strict bed rest did not influence the development of PDPH: The overall incidence was 9.4% in the recumbency group and 8.8% in the group of early ambulation. In all, 45 patients suffered from ordinary not posture-related headache. CONCLUSIONS: The significantly higher incidence of PDPH after spinal anaesthesia with 26-gauge Quincke needles compared to the 27-gauge Quincke and the 26-gauge Atraucan group confirmed the importance of both needle diameter and design of its tip. The Atraucan cannula has not been examined in a controlled study (in comparison with Quincke needle of the same diameter) before. In accordance with other investigators we found patient's age and number of puncture attempts as additional predictors of PDPH. Consequent bed rest, however, was not able to reduce its incidence. Our studies reveal the poor compliance of patients with regard to mobilization/immobilization, a problem which possibly has not been considered enough in former studies examining the influence of bed rest on PDPH. Based on the literature and the present findings, we recommend using thin needles with atraumatic tips for spinal anaesthesia if possible. Recumbency presents an avoidable stress for patients as well as medical staff and should no longer be ordered.

Adolescent↗

AWD 140-190: a new anticonvulsant with a very good margin of safety.

The anticonvulsant activity of the novel drug AWD 140-190 (4-(p-bromophenyl)-3-morpholino-1H-pyrrole-2-carboxylic acid methyl ester) was evaluated in animal models of epileptic seizures. AWD 140-190 was active at nontoxic doses after oral and intraperitoneal administration in rats and mice in a range of anticonvulsant tests. The compound was active against electrically-induced seizures (MES, ED50 rat p.o. = 2.47 mg/kg), in a genetic animal model the DBA/2 mouse, and in corneally kindled rats. It was not active against seizures induced chemically by pentylenetetrazole, bicuculline and strychnine. Effective doses in mice following both oral and intraperitoneal administration are similar indicating good oral absorption. During 14 days chronic oral treatment of mice with 10 mg/kg, no development of tolerance was observed. The protective indices (TD50/MES ED50) in rats and mice following oral administration are favorable when compared to phenytoin, carbamazepine and valproate. No motor impairment, evaluated with the rotarod test and by observation in the open field test, was observable following oral administration of doses up to 500 mg/kg. There was no influence on spontaneous motility and learning performance in rats and no interaction with ethanol in mice after administration of doses which are above anticonvulsant effective doses indicating the absence of central side effects. AWD 140-190 thus presents an orally active and safe anticonvulsant agent, which is structurally unrelated to anticonvulsants currently used.

Animals↗

D-21266, a new heterocyclic alkylphospholipid with antitumour activity.

The aim of this study was to determine the antitumour effects of D-21266 in a rodent tumour model. Hexadecylphosphocholine (INN: Miltefosine) represents the first anticancer agent which was specifically formulated for topical use in cancer patients. The development as an oral drug was hampered by the gastrointestinal toxicity. Hexadecylphosphocholine derivatives were sought with a better therapeutic index. Octadecyl-(1,1-dimethyl-4-piperidylio) phosphate (D-21266) was identified as a suitable candidate. This compound is highly active in vitro inhibiting the growth of a number of human cancer cell lines. Mammary carcinomas were induced in Sprague-Dawley rats using DMBA, and oral doses of D-21266, in various schedules, were given to the animals. A high antineoplastic potency was observed without inducing loss of body weight at highly effective doses. The antitumour effect could be enhanced by introducing a dose schedule consisting of a high loading dose followed by a low maintenance dose, both of which are only marginally active when given alone. Therefore, D-21266 with its favourable pharmacological and toxicological profile, warrants evaluation in the clinic. However, the concept of clinical trials requires new approaches to dose finding and response evaluation, because the dose-response relationship of this compound is distinctly different from that of classical cytostatic agents.

9,10-Dimethyl-1,2-benzanthracene↗

Treatment of uterine leiomyomas with luteinizing hormone-releasing hormone antagonist Cetrorelix.

The efficacy of the luteinizing hormone-releasing hormone antagonist Cetrorelix (SB-75) in the medical management of uterine leiomyomas (fibromas) was evaluated. Cetrorelix was administered to 18 pre-menopausal women with myomas with a mean age of 33.3 years, who had been candidates for hysterectomy. The initial dose of Cetrorelix was 5 mg twice daily s.c. for the first 2 days and thereafter 0.8 mg was given twice daily s.c. for at least 3 months. The mean duration of the treatment was 4.4 months. Before the therapy with Cetrorelix, the mean uterine volume, measured by ultrasonography, was 395.4 +/- 69.2 ml (range 89-1166). Sixteen patients showed a progressive reduction in uterine volume from 410.4 +/- 77.1 to a mean of 230.8 +/- 52.6 ml at 3 months. All patients became amenorrhoeic and had hot flushes. After treatment with Cetrorelix, a surgical myomectomy was performed in 12 women. One of the patients subjected to myomectomy after therapy with Cetrorelix became pregnant. These patients have been followed for up to 25 months and only in one case has the uterine volume increased after therapy. Three patients had good responses to therapy with Cetrorelix and it was decided to follow them only by observation. One patient became pregnant 2 months later. In the other patient, the uterine volume remained unchanged for the duration of the follow-up of 2 years and the third patient showed an increase after 21 months. In three patients, it was necessary to perform total hysterectomy. In 14 patients, serum concentrations of luteinizing hormone, follicle stimulating hormone and oestradiol decreased after the administration of the first dose of Cetrorelix and continued at subnormal values throughout therapy. In 15 patients who were not subjected to total hysterectomy, menstrual function returned at 1 month after cessation of treatment. Overall results support the use of Cetrorelix for the management of uterine leiomyomas.

Adult↗

Characterization of the Chlamydia trachomatis vacuole and its interaction with the host endocytic pathway in HeLa cells.

Chlamydia trachomatis, an obligate intracellular parasite and a major human pathogen, invades eukaryotic host cells and replicates within a membrane-bound compartment (termed the vacuole or inclusion) in the cytoplasm of the host cell. In this report, we describe in detail the characteristics of the vacuole throughout the chlamydial life cycle in terms of the endocytic pathway, as determined by epifluorescent and confocal immunofluorescence microscopy. By indirect immunofluorescence, the transferrin receptor (TfR), a component of early endosomes, and the cation-independent mannose-6-phosphate receptor (CI-M6PR), a component of late endosomes, were found in close association with the chlamydial vacuole as early as 4 h postinfection (hpi) and as late as 20 hpi. Fluorescein isothiocyanate (FITC)-labeled Tf was also found to colocalize with the vacuole at 4, 12, and 20 hpi, indicating that exogenously added ligands can be transported to the region of the vacuole. Antibodies to several different lysosomal proteins failed to label the chlamydial vacuole at any time point during the life cycle. Indirect immunofluorescence of cells infected with chlamydiae stained with an antibody to the trans-Golgi network (TGN) protein TGN38 demonstrated that in infected cells, the integrity and structure of the TGN was altered. The rates of Tf recycling in infected and uninfected cells were compared by fluorescence microscopy and quantitated with 125I-Tf. While the rate of FITC-Tf recycling from endocytic compartments in chlamydia-infected cells did not appear different from that of uninfected cells, a small pool of FITC-Tf that had accumulated adjacent to the chlamydial vacuole recycled at a slower rate. Quantitation of Tf recycling with 125I-Tf showed that Tf was recycled more slowly in infected cells than in uninfected cells. The altered distribution of several endocytic pathway markers and the slowed Tf recycling are consistent with the hypothesis that the chlamydial vacuole interacts with the endocytic pathway of the host. These results furthermore suggest that the chlamydial vacuole does not correspond to a canonical endocytic compartment but that it is a unique and dynamic organelle that shares several characteristics with recycling endosomes of the host cell. Interactions with the early and/or late endosomal compartments, in addition to the Golgi apparatus, may provide a source of membrane or nutrients for the replicating organisms.

Biomarkers↗

Glutamate currents in morphologically identified human dentate granule cells in temporal lobe epilepsy.

Glutamate-receptor-mediated synaptic transmission was studied in morphologically identified hippocampal dentate granule cells (DGCs; n = 31) with the use of whole cell patch-clamp recording and intracellular injection of biocytin or Lucifer yellow in slices prepared from surgically removed medial temporal lobe specimens of epileptic patients (14 specimens from 14 patients). In the current-clamp recording, low-frequency stimulation of the perforant path generated depolarizing postsynaptic potentials that consisted of excitatory postsynaptic potentials and phase-inverted inhibitory postsynaptic potentials mediated by the gamma-aminobutyric acid-A (GABA(A)) receptor at a resting membrane potential of -62.7 +/- 2.0 (SE) mV. In the voltage-clamp recording, two glutamate conductances, a fast alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-receptor-mediated excitatory postsynaptic current (EPSC; AMPA EPSC) and a slowly developing N-methyl-D-aspartate (NMDA)-receptor-mediated EPSC (NMDA EPSC), were isolated in the presence of a GABA(A) receptor antagonist. NMDA EPSCs showed a voltage-dependent increase in conductance with depolarization by exhibiting an N-shaped current-voltage relationship. The slope conductance of the NMDA EPSC ranged from 1.1 to 9.4 nS in 31 DGCs, reaching up to twice the size of the AMPA conductance. This widely varying size of the NMDA conductance resulted in the generation of double-peaked EPSCs and a nonlinear increase of the slope conductance of up to 37.5 nS with positive membrane potentials, which resembled "paroxysmal currents," in a subpopulation of the neurons. In contrast, AMPA EPSCs, which were isolated in the presence of an NMDA receptor antagonist (2-amino-5-phosphonovaleric acid), showed voltage-independent linear changes in the current-voltage relationship and were blocked by 6-cyano-7-nitroquinoxaline-2,3-dione. The AMPA conductance showed little variance, regardless of the size of the NMDA conductance of a given neuron. The average AMPA slope conductance was 5.28 +/- 0.65 (SE) nS in 31 human DGCs. This value was similar to AMPA EPSC conductances in normal rat DGCs (5.35 +/- 0.52 nS, mean +/- SE; n = 55). Dendritic morphology and spine density were quantified in the individual DGCs to assess epileptic pathology. Dendritic spine density showed an inverse correlation (r2 = 0.705) with a slower rise time and a longer half-width of the excitatory postsynaptic potentials mediated by the NMDA receptor. It is concluded that both AMPA and NMDA EPSCs contribute to human DGC synaptic transmission in epileptic hippocampus. However, a wide range of changes in the slope conductance of the NMDA EPSCs suggests that the NMDA-receptor-mediated conductance could be altered in human epileptic DGCs. These changes may influence the generation of chronic subthreshold epileptogenic synaptic activity and give rise to pathological excitation leading to epileptic seizures and dendritic pathology.

Animals↗

Long-term follow-up after temporal lobe resection for lesions associated with chronic seizures.

A follow-up study was conducted on 60 patients who had standard en bloc anterior temporal lobe resection, including mesio-temporal structures, as treatment for temporal lobe lesions associated with chronic, medically intractable seizures. Lesions were identified as glial tumors, hamartomas, or vascular malformations. Long-term outcome was assessed in terms of seizure frequency and certain psychosocial sequelae. Seizure onset occurred at an average age of 15 years (median = 13.5 years), and patients experienced seizures for an average of 13 years prior to surgery. The mean time of follow-up was 8.4 years post-surgery (median = 6 years). The Kaplan-Meier curve at median follow-up showed a seizure-free rate of 80%. Late seizure recurrence was documented for three patients; two had been seizure free for 10 years and one for 15 years after surgery before re-onset of seizures in the absence of tumor recurrence. A prolonged history of seizures prior to surgery was associated with a poorer seizure outcome (p = 0.06), suggesting that secondary epileptogenesis at sites distant to the lesion may develop with years of uncontrolled seizures. There was a low tumor recurrence rate of 3.3% (two cases). The psychosocial outcome was generally good, with 67% working or engaged in educational studies, and improvement noted in 59% of cases for one or more of the psychosocial factors investigated. This study confirms that anterior temporal lobe resection for temporal lesions associated with chronic seizures is a successful treatment with a high seizure-free rate following surgery and good psychosocial outcome.

Adaptation, Psychological↗

Long-term follow-up after temporal lobe resection for lesions associated with chronic seizures.

A follow-up study was conducted on 60 patients who had standard en bloc anterior temporal lobe resection, including mesiotemporal structures, as treatment for temporal lobe lesions associated with chronic, medically intractable seizures. Lesions were identified as glial tumors, hamartomas, or vascular malformations. Long-term outcome was assessed in terms of seizure frequency and certain psychosocial sequelae. Seizure onset occurred at an average age of 15 years (median = 13.5 years), and patients experienced seizures for an average of 13 years prior to surgery. The mean time of follow-up was 8.4 years postsurgery (median = 6 years). The Kaplan-Meier curve at median follow-up showed a seizure-free rate of 80%. Late seizure recurrence was documented for three patients; two had been seizure-free for 10 years and one for 15 years after surgery, before re-onset of seizures in the absence of tumor recurrence. A prolonged history of seizures prior to surgery was associated with a poorer seizure outcome (p = 0.06), suggesting that secondary epileptogenesis at sites distant to the lesion may develop with years of uncontrolled seizures. There was a low tumor recurrence rate of 3.3% (two cases). The psychosocial outcome was generally good, with 67% working or engaged in educational studies, and improvement noted in 59% of cases for one or more of the psychosocial factors investigated. This study confirms that anterior temporal lobe resection for temporal lesions associated with chronic seizures is a successful treatment with a high seizure-free rate following surgery and good psychosocial outcome.

Adaptation, Psychological↗

The crystal structure of a five-stranded coiled coil in COMP: a prototype ion channel?

Oligomerization by the formation of alpha-helical bundles is common in many proteins. The crystal structure of a parallel pentameric coiled coil, constituting the oligomerization domain in the cartilage oligomeric matrix protein (COMP), was determined at 2.05 angstroms resolution. The same structure probably occurs in two other extracellular matrix proteins, thrombospondins 3 and 4. Complementary hydrophobic interactions and conserved disulfide bridges between the alpha helices result in a thermostable structure with unusual properties. The long hydrophobic axial pore is filled with water molecules but can also accommodate small apolar groups. An "ion trap" is formed inside the pore by a ring of conserved glutamines, which binds chloride and probably other monatomic anions. The oligomerization domain of COMP has marked similarities with proposed models of the pentameric transmembrane ion channels in phospholamban and the acetylcholine receptor.

Amino Acid Sequence↗

Homophilic adhesion of E-cadherin occurs by a co-operative two-step interaction of N-terminal domains.

Cluster formation of E-cadherin on the cell surface is believed to be of major importance for cell-cell adhesion. To mimic this process the extracellular part of mouse E-cadherin (ECAD) was recombinantly fused to the assembly domain of rat cartilage oligomeric matrix protein (COMP), resulting in the chimeric protein ECAD-COMP. The COMP domain formed a five-stranded alpha-helical coiled-coil. This enabled the formation of a pentameric ECAD with bundled C-termini and free N-termini. The pentameric protein construct ECAD-COMP and the monomeric ECAD were expressed in human embryonal kidney 293 cells. Electron microscopy, analytical ultracentrifugation, solid phase binding and cell attachment assays revealed that pentamers showed strong self-association and cell attachment, whereas monomers exhibited no activity. At the high internal concentration in the pentamer the N-terminal EC1 domains of two E-cadherin arms interact to form a ring-like structure. Then the paired domains interact with a corresponding pair from another pentamer. None of the four other extracellular domains of E-cadherin is involved in this interaction. Based on these results, an in vivo mechanism is proposed whereby two N-terminal domains of neighbouring E-cadherins at the cell surface first form a pair, which binds with high affinity to a similar complex on another cell. The strong dependence of homophilic interactions on C-terminal clustering points towards a regulation of E-cadherin mediated cell-cell adhesion via lateral association.

Amino Acid Sequence↗

Interspike intervals during interictal periods in human temporal lobe epilepsy.

We recorded 259 single neurons from mesial temporal lobe structures of 21 patients with complex partial seizures. Interspike intervals within clusters of action potentials (clustered interspike intervals) recorded from cells in mesial temporal structures ipsilateral to seizure initiation were compared to clustered interspike intervals in the contralateral temporal lobe. 'Clusters' were defined as any group of three or more spikes separated by intervals of less than a defined maximum, or two spikes separated by less than half that maximum. The maximum interspike interval which defined a cluster was varied from 5 to 40 ms in 5-ms steps. Significantly smaller proportions of clustered spikes were discharged by neurons in the amygdala, hippocampus and entorhinal cortex from the temporal lobe commonly initiating seizures, compared to neurons in contralateral homotopic regions. When data from the same three structures were combined, significantly fewer cluster interspike intervals between 10 and 25 ms were recorded from cells on the side of seizure onset. Because clustered action potential discharge is a normal pattern of firing for cells that discharge endogenous bursts, the relative decrease in proportions of 10-25 ms clustered interspike intervals occurring in the temporal lobe initiating seizures might reflect a reduction in endogenous burst discharges from that side. Reduced endogenous bursting could be due to the loss of burst discharging neurons as a product of seizure-related excitotoxicity. The identification of decreased interictal single neuronal burst discharge in epileptogenic structures stresses the difference between the interictal and ictal states in patients with complex partial seizures, and the importance of the transition between those states.

Action Potentials↗