Current approaches to the use of generic antiepileptic drugs

Generic substitution is encouraged as a cost containment strategy for the management of health care resources. However, in epilepsy, the consequences of loss of symptom control are important, and antiepileptic drugs have narrow therapeutic indices. For this reason, generic substitution may be problematic, and certain health authorities have excluded antiepileptic drugs from overall policy recommendations on generic prescribing. The absence of bioequivalence data among generic forms and the relatively broad criteria for bioequivalence with the branded drug allow differences in drug exposure to arise that may be clinically relevant and necessitate monitoring of plasma levels when switching formulations to avoid loss of seizure control or emergence of side effects. Management of these issues carries a significant cost, which should be weighed carefully against the cost savings acquired when purchasing the drug. Both physicians and patients have a right to be informed and approve before pharmacists make a generic substitution or switch between generics.     

On the best strategies on the best results for surgery of frontal epilepsy

Frontal lobe epilepsy surgery is the second most common surgery performed for drug-resistant partial epilepsy. We investigated the longitudinal outcome in a cohort of patients investigated since 1990 with SEEG and modern diagnostic techniques. We reviewed 105 patients who underwent surgery between 1990 and 2005 (mean follow-up, six years; range: one to17 years) and analyzed the year-per-year follow-up according to Engel's classification. Favorable outcome (Class I) was observed for 70% and this result was stable at least five years after surgery. More than 90% of patients with lesion-related epilepsies (focal cortical dysplasia and dysembryoplastic neuroepithelial tumors) became seizure-free. Less than 50% of patients classified as having cryptogenic epilepsy (defined as normal imaging and neuropathology on surgical specimen) had a favorable outcome.Permanent neurological sequelae were subtle and rare, especially after surgery for dysplasia in eloquent cortex (primary motor cortex).Our data indicate that frontal surgery is a successful treatment in patients when electrophysiological and morphological investigations demonstrate a well-defined epileptogenic zone or lesion to be surgically resected. Progress in electrophysiological and brain-imaging techniques will further improve the selection of frontal lobe epilepsy surgery candidates.     

Occupational blood and body fluids exposures in health care workers: four-year surveillance from the Northern France network

The risk of accidental blood and body fluid (BBF) exposure is a daily concern for health care workers throughout the world, and various strategies have been introduced during the past decade to help reduce that risk. To assess the impact of multifocal reduction strategies introduced in hospitals affiliated with the Northern France network, we recently examined data from 4 years of BBF-exposure reports filed by network employees. A total of 7,649 BBF exposures were reported by health care workers to occupational medicine departments in 61 hospitals. Nurses and nursing students accounted for 4,587 (60%) of exposures, followed by nurses' aides and clinicians. Most (77.6%) of the reports were related to needlestick injury (NSI). In addition, we examined BBF exposure trends over time by analyzing data from 18 hospitals (29.5%) with data available for the time period of 1995 to 1998. These were assessed in nurses, who have the highest and most consistent reporting rate. We noted that the BBF-exposure incidence rate for all BBF exposures in nurses decreased from 10.8 to 7.7 per 100 nurses per year between 1995 and 1998 (P <.001), whereas the NSI rate decreased 8.9 per 100 nurses per year in 1995 to 6.3 in 1998 (P <.001). The percentage of NSIs that resulted from noncompliance with universal precautions also decreased significantly (P =.04). Widespread improvements in procedures and engineering controls were implemented in the Northern France network before and during the study period. Significant reductions were observed in reports of BBF exposures and NSIs, particularly in nurses. These findings are similar to those in other countries and reflect the overall improvement in the management of occupational risk of BBF in health care workers.     

From anatomic standardization analysis of perfusion SPECT data to perfusion pattern modeling: evidence of functional networks in healthy subjects and temporal lobe epilepsy patients

RATIONALE AND OBJECTIVES: In the general context of perfusion pattern modeling from single-photon emission computed tomographic (SPECT) data, the purpose of this study is to characterize interindividual functional variability and functional connectivity between anatomic structures in a set of SPECT data acquired from a homogeneous population of subjects. MATERIALS AND METHODS: From volume of interest (VOI)-perfusion measurements performed on anatomically standardized SPECT data, we proposed to use correspondence analysis (CA) and hierarchical clustering (HC) to explore the structure of statistical dependencies among these measurements. The method was applied to study the perfusion pattern in two populations of subjects; namely, SPECT data from 27 healthy subjects and ictal SPECT data from 10 patients with mesio-temporal lobe epilepsy (MTLE). RESULTS: For healthy subjects, anatomic structures showing statistically dependent perfusion patterns were classified into four groups; namely, temporomesial structures, internal structures, posterior structures, and remaining cortex. For patients with MTLE, they were classified as temporomesial structures, surrounding temporal structures, internal structures, and remaining cortex. Anatomic structures of each group showed similar perfusion behavior so that they may be functionally connected and may belong to the same network. Our main result is that the temporal pole and lenticular nucleus seemed to be highly relevant to characterize ictal perfusion in patients with MTLE. This exploratory analysis suggests that a network involving temporal structures, lenticular nucleus, brainstem, and cerebellum seems to be involved during MTLE seizures. CONCLUSION: CA followed by HC is a promising approach to explore brain perfusion patterns from SPECT VOI measurements.     

Involvement of the basal ganglia in refractory epilepsy: an 18F-fluoro-L-DOPA PET study using 2 methods of analysis.

Studies in animal models and epileptic patients have led to the suggestion that the basal ganglia (BG) are involved in seizures. PET with 6-18F-L-3,4-fluorodihydroxyphenylalanine (18F-fluoro-L-DOPA) has recently demonstrated a reduction of striatal dopamine uptake in drug-resistant epileptic patients with ring chromosome 20 (r20) using a multiple-time graphical analysis. The aim of the present study was to evaluate the involvement of dopamine in other epileptic syndromes using a multiple-time graphical analysis and the all-brain statistical parametric mapping (SPM) analysis. METHODS: Patients with drug-resistant epilepsy were divided into 3 groups: group 1, with r20 epilepsy (n = 16; mean age +/- SD, 21.5 +/- 5.4 y); group 2, with resistant generalized "absence-like" epilepsy (n = 10; mean age, 32.3 +/- 11.4 y); and group 3, with drug-resistant temporal lobe epilepsy with hippocampal sclerosis (n = 9; mean age, 35.2 +/- 10.3 y). We compared 2 strategies of analysis of the 18F-fluoro-L-DOPA uptake constant (K(i), min(-1)) in BG using a multiple-time graphical analysis using regions of interest (the gold-standard method) and an SPM analysis using a voxel-by-voxel statistical t test to avoid a priori hypotheses in the analysis. Each epileptic group was compared with a group of healthy volunteers (n = 10; mean age, 45.1 +/- 16.5 y). RESULTS: A decrease of the mean K(i) value was observed in the striatum in all groups of patients with both types of analysis. With multiple-time graphical analysis, the reduction was evident using the averaged K(i) values over both hemispheres in each BG. Unilateral decreases in each BG were detected in SPM analysis. A ratio of decrease of 18F-fluoro-L-DOPA uptake was observed in the 3 groups of patients. Only the SPM analysis showed a decrease of 18F-fluoro-L-DOPA uptake ipsilateral to the seizure side in patients with temporal lobe epilepsy. Moreover, the all-brain SPM analysis showed a decrease of 18F-fluoro-L-DOPA uptake in the substantia nigra bilaterally (P < 0.001). CONCLUSION: This result confirms the involvement of dopamine neurotransmission in seizure control related to the type of epileptic syndrome. The difference in epileptic types may depend in part on the seizure frequency.