Faculty Bibliography

Substance P (SP) is known to be a peptide that facilitates epileptic activity of principal cells in the hippocampus. Paradoxically, in other models, it was found to be protective against seizures by activating substance P receptor (SPR)-expressing interneurons. Thus, these cells appear to play an important role in the generation and regulation of epileptic seizures. The number, distribution, morphological features and input characteristics of SPR-immunoreactive cells were analyzed in surgically removed hippocampi of 28 temporal lobe epileptic patients and eight control hippocampi in order to examine their changes in epileptic tissues. SPR is expressed in a subset of inhibitory cells in the control human hippocampus, they are multipolar interneurons with smooth dendrites, present in all hippocampal subfields. This cell population is considerably different from SPR-positive cells of the rat hippocampus. The CA1 (cornu Ammonis subfield 1) region was chosen for the detailed morphological analysis of the SPR-immunoreactive cells because of its extreme vulnerability in epilepsy. The presence of various neurochemical markers identifies functionally distinct interneuron types, such as those responsible for perisomatic, dendritic or interneuron-selective inhibition. We found considerable colocalization of SPR with calbindin but not with parvalbumin, calretinin, cholecystokinin and somatostatin, therefore we suppose that SPR-positive cells participate mainly in dendritic inhibition. In the non-sclerotic CA1 region they are mainly preserved, whereas their number is decreased in the sclerotic cases. In the epileptic samples their morphology is considerably altered, they possessed more dendritic branches, which often became beaded. Analyses of synaptic coverage revealed that the ratio of symmetric synaptic input of SPR-immunoreactive cells has increased in epileptic samples. Our results suggest that SPR-positive cells are preserved while principal cells are present in the CA1 region, but show reactive changes in epilepsy including intense branching and growth of their dendritic arborization

PURPOSE: To determine whether epidural pentobarbital (PB) delivery can prevent and/or terminate neocortical seizures induced by locally administered acetylcholine (Ach) in freely moving rats. METHODS: Rats were implanted permanently with an epidural cup placed over the right parietal cortex with intact dura mater. Epidural screw-electrodes, secured to the cup, recorded local neocortical EEG activity. In the seizure-termination study, Ach was delivered into the epidural cup, and after the development of electrographic and behavioral seizures, the Ach solution was replaced with either PB or artificial cerebrospinal fluid (aCSF; control solution). In the seizure-prevention study, the epidural Ach delivery was preceded by a 10-min exposure of the delivery site to PB or aCSF. Raw EEG recordings, EEG power spectra, and behavioral events were analyzed. RESULTS: Ach-induced EEG seizures associated with convulsions, which were unaffected by epidural aCSF applications, were terminated by epidurally delivered PB within 2-2.5 min. Epidural deliveries of PB before Ach applications completely prevented the development of electrographic and behavioral seizures, whereas similar deliveries of aCSF exerted no influence on the seizure-generating potential of Ach. CONCLUSIONS: This study showed for the first time that epidural AED delivery can prevent, as well as terminate, locally induced neocortical seizures. The findings support the viability of transmeningeal pharmacotherapy for the treatment of intractable neocortical epilepsy

BACKGROUND: Several risk factors have been attributed to seizure recurrence after surgery. It is unknown whether race/ethnicity plays a role in outcome. OBJECTIVE: To evaluate whether race/ethnicity plays a role in seizure recurrence after surgery. DESIGN: Cohort study. SETTING: We evaluated data obtained from the epilepsy centers at the University of Alabama at Birmingham and New York University, New York, NY. PATIENTS: All patients included had a diagnosis of mesial temporal sclerosis and underwent temporal lobectomy. MAIN OUTCOME MEASURES: Occurrence of seizure after surgery was registered 1 year after surgery. We used multiple logistic regression analysis to model the presence of seizure recurrence after surgery and generated odds ratios (ORs) for seizure recurrence after surgery for African American and Hispanic patients relative to white patients. An unadjusted model incorporated only race/ethnicity as the independent variable, and an adjusted model included socioeconomic status, age, duration of epilepsy, education, history of febrile seizures, sex, handedness, lateralization of epileptogenic focus, and number of antiepileptics as the independent variables. RESULTS: Two hundred fifty-two patients underwent surgical treatment with pathological confirmation of mesial temporal sclerosis. No differences were found between racial/ethnic groups in terms of seizure recurrence in any models. For African American patients, the ORs were 0.9 (95% confidence interval [CI], 0.4-2.1) for the unadjusted model and 0.8 (95% CI, 0.3-2.0) for the adjusted model; for Hispanic patients, the ORs were 1.6 (95% CI, 0.8-3.2) for the unadjusted model and 1.1 (95% CI, 0.5-2.6) for the adjusted model, relative to white patients. CONCLUSION: Our data suggest that although sex appears to play a role in the outcomes of surgery for temporal lobe epilepsy, race and socioeconomic status do not

OBJECTIVE: To report the technique of subpectoral (SP) implantation of the vagus nerve stimulator (VNS) generator. METHODS: We retrospectively reviewed and compared demographics and complications from patients receiving either subcutaneous (SQ; n = 107) or SP (n = 138) VNS implants, performed by one surgeon (WKD) between 1999 and 2003. Selection of implant location was made during the preoperative surgeon-patient consultation on the basis of surgeon recommendation and patient preference. RESULTS: The standard VNS generator implantation is performed within a SQ pocket in the left infraclavicular region of the chest. We have modified this technique by placing the generator into a deeper pocket SP, beneath the pectoralis major muscle, while tunneling the electrodes SQ in the usual fashion. The SP group was substantially younger (median age 19 yr) compared with the SQ group (median age 29 yr). At an average follow-up of 52 months for SQ implants and 28.4 months for SP implants, there were 2.9% infections per patient in the SQ group and 2.5% infections per patient in the SP group. There were three cases of excessive generator mobility in the SQ group; no cases occurred in the SP group. CONCLUSION: The SP implantation technique provides an attractive alternative to SQ VNS implantation. With increased soft tissue coverage, we provide improved cosmesis, increased wound durability to tampering and trauma, and a comparable infection rate with the SQ group