SPECT activation patterns in psychogenic non-epileptic seizures in temporal lobe epilepsy patients.

INTRODUCTION: The diagnosis of psychogenic non-epileptic seizures (PNES) can often be challenging. When video-electroencephalography (EEG) is not conclusive, single-photon emission computed tomography (SPECT) can be useful by quantifying changes in regional cerebral blood flow (rCBF). METHODS: We conducted a retrospective case-control study in adult patients with pharmacoresistant temporal lobe epilepsy (TLE). Those patients with an ictal SPECT obtained during an event finally diagnosed as PNES were included as cases (PNES+). The control group consisted of patients with TLE without PNES (PNES-). Clinical episodes were analysed and classified according to PNES subtypes. Subtraction ictal SPECT coregistered to MRI (SISCOM) analysis was performed for the detection of areas with significant changes in perfusion compared to individual interictal studies. Group comparisons in SPM12 included paired t-tests of ictal vs. interictal studies in each group of temporal lobe seizures and PNES events. RESULTS: Ten patients with TLE and PNES were included. We found no patterns of regional hyperperfusion typical of TLE seizures during the PNES events. In two of these cases, an ictal SPECT during a confirmed epileptic seizure was also obtained, showing antero-mesial temporal lobe hyperperfusion. Group comparisons between ictal and interictal SPECTs showed increased rCBF in the temporal lobe with reduced perfusion in the default mode network areas and cerebellum during temporal lobe seizures in PNES- patients and decreased perfusion restricted to the posterior parietal cortex without significant rCBF increases in PNES events. CONCLUSIONS: Ictal SPECT can be a helpful tool to characterize rCBF changes in PNES and for differential diagnosis with seizures in TLE patients.

Applicability and contribution of the new ILAE 2017 classification of epileptic seizures and epilepsies.

The aim of the study was to evaluate the clinical applicability of the 2017 ILAE classification of seizures and epilepsies through the analysis of a sample of 100 outpatients with a diagnosis of epilepsy. All clinical charts were reviewed applying both the 1981/1989 and 2017 classifications of seizures and epilepsies, respectively. For most focal seizures, descriptors were required to include all the relevant clinical information. The reclassification of complex partial seizures into focal seizures with impaired awareness with a motor / non-motor onset allowed the inclusion of features of topographic value, although the chronological sequence of awareness impairment was lacking. The use of the term "focal to bilateral tonic-clonic" reduced the number of seizures classified as generalized tonic-clonic seizures (GTCS) by 19%. A subset of GTCS (35%) and absence seizures (12.5%) were reclassified as seizures of unknown onset. Most focal symptomatic epilepsies (92%) were reclassified as focal structural epilepsies, while 27% of idiopathic generalized and 7% of focal cryptogenic epilepsies merged into the category of "epilepsies of unknown type". Major strengths of the new classification are simplicity and the role of the category "unknown onset" to avoid forced categorization. A section assigned to uncertainty reinforces the need for further ancillary studies and periodic diagnostic re-evaluation.

Influence of efflux transporters on drug metabolism: theoretical approach for bioavailability and clearance prediction.

Cytochrome P450 enzymes and efflux transporters, expressed in the intestine and/or in the liver, play important roles in drug clearance and oral bioavailability. The relative contribution of transporters and enzymes in drug metabolism is still controversial. Some antiepileptic drugs, such as carbamazepine, phenytoin and phenobarbital (phenobarbitone), show time-dependent and dose-dependent pharmacokinetics due to their inductive effect on both efflux transporters and enzymes. However, steady-state plasma drug concentrations for each antiepileptic drug do not relate to oral daily dose in the same way, with decreased or increased apparent clearance according to the drug. A multicompartment pharmacokinetic model was developed in order to explain these different behaviours using a single mechanism of inductive action. The key for solving these apparent dissimilarities was to consider in the model the unique physiological connection that intestine, liver and bloodstream have. Efflux transporters not only enhance enzymatic competition in relation to first-order processes, but also change the predominance of some elimination routes. For instance, the carbamazepine-10,11-epoxide formation increases at the expense of other carbamazepine metabolites, enhancing both the systemic and presystemic elimination of parent drug. Conversely, the major hepatic metabolism of phenytoin diminishes in favour of its minor intestinal elimination, decreasing the total drug clearance.

Prodromal symptoms in epileptic patients: clinical characterization of the pre-ictal phase.

Although recent advances in seizure anticipation have been achieved with the development of several biomathematical electroencephalographic (EEG) methods, pre-ictal clinical phenomena have not been extensively investigated. The aim of the study was to thoroughly analyze premonitory or prodromal symptoms (PS) in a randomly selected sample of 100 adult epileptic patients. A semi-structured protocol was used for in-person interviews to both patients and observers. PS were found in 39% of patients, the most frequent ones being behavioral, cognitive and mood changes. Both patients with focal and generalized epilepsies reported prodromes, although they were more frequently found in the former group. PS were mostly perceived preceding complex partial and generalized tonic-clonic seizures. Prodromal symptoms were reported to have an insidious onset and their duration ranged from 30min to several hours. The potential value of prodromes in seizure anticipation would allow the use of preventive and therapeutic measures, including drugs, neurostimulation procedures and behavioral intervention.