Temporal changes in mRNA expression of the brain nutrient transporters in the lithium-pilocarpine model of epilepsy in the immature and adult rat.

The lithium-pilocarpine model mimics most features of human temporal lobe epilepsy. Following our prior studies of cerebral metabolic changes, here we explored the expression of transporters for glucose (GLUT1 and GLUT3) and monocarboxylates (MCT1 and MCT2) during and after status epilepticus (SE) induced by lithium-pilocarpine in PN10, PN21, and adult rats. In situ hybridization was used to study the expression of transporter mRNAs during the acute phase (1, 4, 12 and 24h of SE), the latent phase, and the early and late chronic phases. During SE, GLUT1 expression was increased throughout the brain between 1 and 12h of SE, more strongly in adult rats; GLUT3 increased only transiently, at 1 and 4h of SE and mainly in PN10 rats; MCT1 was increased at all ages but 5-10-fold more in adult than in immature rats; MCT2 expression increased mainly in adult rats. At all ages, MCT1 and MCT2 up-regulation was limited to the circuit of seizures while GLUT1 and GLUT3 changes were more widespread. During the latent and chronic phases, the expression of nutrient transporters was normal in PN10 rats. In PN21 rats, GLUT1 was up-regulated in all brain regions. In contrast, in adult rats GLUT1 expression was down-regulated in the piriform cortex, hilus and CA1 as a result of extensive neuronal death. The changes in nutrient transporter expression reported here further support previous findings in other experimental models demonstrating rapid transcriptional responses to marked changes in cerebral energetic/glucose demand.

Glut-1 deficiency syndrome masquerading as idiopathic generalized epilepsy.

To report the case of a child with short absences and occasional myoclonias since infancy who was first diagnosed with an idiopathic generalized epilepsy, but was documented at follow-up to have a mild phenotype of glucose transporter type 1 deficiency syndrome. Unlike other reported cases of Glut-1 DS and epilepsy, this child had a normal development as well as a normal head growth and neurological examination. Early onset of seizures and later recognized episodes of mild confusion before meals together with persistent atypical EEG features and unexpected learning difficulties led to the diagnosis. Seizure control and neuropsychological improvements were obtained with a ketogenic diet.

Traitement des epilepsies réfractaires: rôle de la stimulation electrique [Treatment of pharmacoresistant epilepsy: stimulated refractoriness].

Antiepileptic drugs allow controlling seizures in 70% of patients. For the others, a presurgical work-up should be undertaken, especially if a focal seizure origin is suspected; however, only a fraction of pharmacoresistant patients will be offered resective (curative) surgery. In the last 15 years, several palliative therapies using extra- or intracranial electrical stimulations have been developed. This article presents the vagal nerve stimulation, the deep brain stimulation (targeting the mesiotemporal region or the thalamus), and the cortical stimulation "on demand". All show an overall long-term responder rate between 30-50%, but less than 5% of patients becoming seizure free. It is to hope that a better understanding of epileptogenic mechanisms and of the implicated neuronal networks will lead to an improvement of these proportions.

Autistic spectrum disorder: evaluating a possible contributing or causal role of epilepsy.

The onset of epilepsy in brain systems involved in social communication and/or recognition of emotions can occasionally be the cause of autistic symptoms or may aggravate preexisting autistic symptoms. Knowing that cognitive and/or behavioral abnormalities can be the presenting and sometimes the only symptom of an epileptic disorder or can even be caused by paroxysmal EEG abnormalities without recognized seizures, the possibility that this may apply to autism has given rise to much debate. Epilepsy and/or epileptic EEG abnormalities are frequently associated with autistic disorders in children but this does not necessarily imply that they are the cause; great caution needs to be exercised before drawing any such conclusions. So far, there is no evidence that typical autism can be attributed to an epileptic disorder, even in those children with a history of regression after normal early development. Nevertheless, there are several early epilepsies (late infantile spasms, partial complex epilepsies, epilepsies with CSWS, early forms of Landau-Kleffner syndrome) and with different etiologies (tuberous sclerosis is an important model of these situations) in which a direct relationship between epilepsy and some features of autism may be suspected. In young children who primarily have language regression (and who may have autistic features) without evident cause, and in whom paroxysmal focal EEG abnormalities are also found, the possible direct role of epilepsy can only be evaluated in longitudinal studies.

Fermat's treatise on quadrature: A new reading

The Treatise on Quadrature of Fermat (c. 1659), besides containing the first known proof of the computation of the area under a higher parabola, R x+m/n dx, or under a higher hyperbola, R x-m/n dx with the appropriate limits of integration in each case , has a second part which was not understood by Fermat s contemporaries. This second part of the Treatise is obscure and difficult to read and even the great Huygens described it as'published with many mistakes and it is so obscure (with proofs redolent of error) that I have been unable to make any sense of it'. Far from the confusion that Huygens attributes to it, in this paper we try to prove that Fermat, in writing the Treatise, had a very clear goal in mind and he managed to attain it by means of a simple and original method. Fermat reduced the quadrature of a great number of algebraic curves to the quadrature of known curves: the higher parabolas and hyperbolas of the first part of the paper. Others, he reduced to the quadrature of the circle. We shall see how the clever use of two procedures, quite novel at the time: the change of variables and a particular case of the formulaof integration by parts, provide Fermat with the necessary tools to square very easily curves as well-known as the folium of Descartes, the cissoid of Diocles or the witch of Agnesi.

Posterior quadrantic epilepsy surgery: technical variants, surgical anatomy, and case series.

OBJECTIVE: Patients with intractable epilepsy due to extensive lesions involving the posterior quadrant (temporal, parietal, and occipital lobes) form a small subset of epilepsy surgery. This study was done with a view to analyze our experience with this group of patients and to define the changes in the surgical technique over the last 15 years. We also describe the microsurgical technique of the different surgical variants used, along with their functional neuroanatomy. METHODS: In this series there were 13 patients with a median age of 17 years. All patients had extensive presurgical evaluation that provided concordant evidence localizing the lesion and seizure focus to the posterior quadrant. The objective of the surgery was to eliminate the effect of the epileptogenic tissue and preserve motor and sensory functions. RESULTS: During the course of this study period of 15 years, the surgical procedure performed evolved toward incorporating more techniques of disconnection and minimizing resection. Three technical variants were thus utilized in this series, namely, (i) anatomical posterior quadrantectomy (APQ), (ii) functional posterior quadrantectomy (FPQ), and (iii) periinsular posterior quadrantectomy (PIPQ). After a median follow-up period of 6 years, 12/13 patients had Engel's Class I seizure outcome. CONCLUSION: The results of surgery for posterior quadrantic epilepsy have yielded excellent seizure outcomes in 92% of the patients in the series with no mortality or major morbidity. The incorporation of disconnective techniques in multilobar surgery has maintained the excellent results obtained earlier with resective surgery.

Traitement médicamenteux actuel de l'épiepsie [Current drug treatment for epilepsy]

If one patient is diagnosed with epilepsy, the first treatment line is represented by medications, which allow a seizure control in at least 2/3 of patients. Following the steady development of new compounds, there are currently more than 20 antiepileptic agents on the market, and several more will appear in the near future. This review, focusing on the indications and pitfalls of the most used drugs, with a particular attention to the new ones, aims at improving the orientation among this multitude of options. Since there is almost no difference regarding the efficacy on seizures, it is rather the profile of comorbidities and possible (positive and negative) side effects that will allow to select the best antiepileptic drug for each specific clinical situation, permitting a patient-tailored approach.

Epilepsy meets cancer: when, why, and what to do about it?

The lifetime risk of having epileptic seizures is profoundly increased in patients with cancer: about 20% of all patients with systemic cancer may develop brain metastases. These patients and those with primary brain tumours have a lifetime risk of epilepsy of 20-80%. Moreover, exposure to chemotherapy or radiotherapy to the brain, cancer-related metabolic disturbances, stroke, and infection can provoke seizures. The management of epilepsy in patients with cancer includes diagnosis and treatment of the underlying cerebral pathological changes, secondary prophylaxis with antiepileptic drugs, and limiting of the effect of epilepsy and its treatment on the efficacy and tolerability of anticancer treatments, cognitive function, and quality of life. Because of the concern of drug-drug interactions, the pharmacological approach to epilepsy requires a multidisciplinary approach, specifically in a setting of rapidly increasing choices of agents both to treat cancer and cancer-associated epilepsy.

Variation in performance across Swiss mammography screening programmes: the influence of reading strategy and experience.

[Abstract] Reading volume and mammography screening performance appear positively correlated. Performance was compared across organised Swiss screening programmes, which target relatively small populations. Except for accreditation of 2nd readers radiologists (restrictive vs non-restrictive strategy), Swiss programmes have similar screening regimen/procedures and duration, which maximises comparability. Variation in performance was explored in order to improve mammography practice and optimise screening performance. Indicators of quality and effectiveness were evaluated for about 200,000 screens performed over 4 screening rounds in the 3 longest-standing Swiss cantonal programmes (of Vaud, Geneva and Valais). Interval cancers were identified by linkage with cancer registries records. Most European standards of performance were met with a favourable cancer stage shift. Several performance indicators showed substantial variation across programmes. In subsequent rounds, compared with programmes (Vaud and Geneva) which accredited few 2nd readers to increase their individual reading volume, proportions of in situ lesions and of small cancers (? 1cm) were one third lower and halved, respectively, and the proportion of advanced lesions (stage II+) nearly 50% higher in the programme without a restrictive selection strategy. Discrepancy in second-year proportional incidence of interval cancers appears to be multicausal. Differences in performance could partly be explained by a selective strategy for 2nd readers and a prior experience in service screening, but not by the levels of opportunistic screening and programme attendance. This study provides clues for enhancing mammography screening performance in low-volume Swiss programmes.

The yield of high-density electric source imaging in focal epilepsy

Background: EEG is the cornerstone of epilepsy diagnostics and mandatory to determine the underlying epilepsy syndrome (e.g. focal vs idiopathic generalized). However, its potential as imaging tool is still underrecognized. In the present study, we aim to determine the prerequisites of maximal benefit of electric source imaging (ESI) to localize the irritative zone in patients with focal epilepsy. Methods: 150 patients suffering from focal epilepsy and with minimum 1 year post-operative follow-up were studied prospectively by reviewers blinded to the underlying diagnosis and outcome. We evaluated the influence of two important factors on sensitivity and specificity of ESI: the number of electrodes (low resolution, LR-ESI: \30 vs. high resolution, HR-ESI: 128-256 electrodes), and the use of individual MRI (i-MRI) vs. template MRI (t-MRI) as head model.Results: ESI had a sensitivity of 85% and a specificity of 87% when HR-ESI with i-MRI was used. Using LR-ESI, sensitivity decreased to 68%, or even 57% when only t-MRI was available. The sensitivity of HR-ESI/i-MRI compared favorably with those of MRI (76%), PET (69%) and ictal/interictal SPECT (64%).Interpretation: This study on a large patient group shows excellent sensitivity and specificity of ESI if 128 EEG channels or more are used for ESI and if the results are co-registered to the patient's individual MRI. Localization precision is as high as or even higher than established brain imaging techniques, providing excellent costeffectiveness in epilepsy evaluation. HR-ESI appears to be a valuable additional imaging tool, given that larger electrode arrays are easily and rapidly applied with modern EEG equipment and that structural MRI is nearly always available for these patients.

Neuropsychological outcome after extra-temporal epilepsy surgery.

BACKGROUND: The neuropsychological results of temporal lobe epilepsy surgery are well reported in the literature. The aim of this study was to analyse the neuropsychological outcome in a consecutive series of patients with extra-temporal epilepsy. METHODS: We retrospectively analysed the data of patients operated between 1996 and 2008 for extra-temporal epilepsy. Standard neuropsychological tests were applied. We assessed the neuropsychological outcome after surgery and the correlation of the neuropsychological outcome with (1) side and localisation of surgery, (2) Engel scale for seizure outcome and (3) timing of surgery. FINDINGS: Patients had a better neuropsychological outcome when undergoing non-frontal resection [χ2 (2) =6.66, p = 0.036]. Subjects who had undergone left or right resection showed no difference in outcome [χ2 (2) =0.533, p = 0.766]. The correlation between the Engel scale for seizure re-occurence and the neuropsychological scores showed only a tendency for better outcome (Spearman ρ = -0.437; p = 0.069). The global measure of change did not correlate significantly with delay of surgery (Spearman ρ = -0.163; p = 0.518). CONCLUSIONS: Resective epilepsy surgery improves neuropsychological status outcome in patients with extra-temporal epilepsy even if the patient did not become seizure free. The outcome is better for non-frontal localisation.