Mar Carreño

Neuropsychological tests with lateralizing value in patients with temporal lobe epilepsy: Reconsidering material-specific theory

PURPOSEnTo assess the ability of neuropsychological tests to determine the side of seizure onset for preoperative assessment in patients with drug-resistant temporal lobe epilepsy.nnnMETHODSnTwenty-nine consecutive patients diagnosed with temporal lobe epilepsy (TLE), in whom the epileptogenic focus was clearly identified and localized to either the right or left hemisphere. Patients underwent a full neuropsychological assessment as part of their pre-surgical investigation, including the Boston Naming Test (BNT) and a variety of Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) and Wechsler Memory Scale-Third Edition (WMS-III) subtests. Two multivariate analyses of variance were carried out to assess differences on memory and language measures between groups according to side of epileptogenic focus. Binary logistic regression analysis was performed to find the sets of tests that best predicted the side of seizure onset (determined by EEG and MRI).nnnRESULTSnMemory multivariate analysis of variance failed to show significant differences between the right- and left-sided groups. Among language measures, only the BNT revealed significant differences between the groups. The neuropsychological measures that best predicted the side of seizure onset were the BNT and Visual Reproduction II.nnnCONCLUSIONSnLanguage measures predict the side of seizure focus better than memory measures. The results of this study in a sample of drug-resistant temporal lobe epilepsy patients challenge the memory material-specific theory for the side of seizure focus.

Parry Romberg syndrome and linear scleroderma in coup de sabre mimicking Rasmussen encephalitis.

We present one patient with Parry Romberg syndrome and another with linear scleroderma in coup de sabre, with focal neurologic deficits and intractable seizures arising from the hemisphere ipsilateral to the cutaneous lesion. Brain MRI showed progressive hemispheric atrophy. Pathology after functional hemispherectomy showed chronic inflammatory features suggestive of Rasmussen encephalitis.We present one patient with Parry Romberg syndrome and another with linear scleroderma in coup de sabre, with focal neurologic deficits and intractable seizures arising from the hemisphere ipsilateral to the cutaneous lesion. Brain MRI showed progressive hemispheric atrophy. Pathology after functional hemispherectomy showed chronic inflammatory features suggestive of Rasmussen encephalitis.

Hemispheric malformations of cortical development

The term hemispheric malformations of cortical development (MCDs) is used in this article to represent congenital malformations that predominantly or exclusively involve complete or substantial portion of one cerebral hemisphere. Hemispheric MCDs usually present during early childhood with intractable epilepsy, cognitive delay, and contralateral hemiparesis. Early identification and selection of children who may be candidates for epilepsy surgery are important during diagnostic evaluation of hemispheric MCD. Surgical intervention at an appropriate time, whenever possible, offers the best chance for seizure freedom and improved cognitive outcome. In addition, making an accurate genetic diagnosis is imperative to offer genetic testing and counseling to the family. In this article, the authors discuss the developmental and genetic mechanisms, pathologic features, diagnosis, and treatment of hemispheric MCD that are substrates of catastrophic childhood epilepsy amenable to surgical treatment.

PET/MRI and PET/MRI/SISCOM coregistration in the presurgical evaluation of refractory focal epilepsy

We aimed to investigate the usefulness of coregistration of positron emission tomography (PET) and magnetic resonance imaging (MRI) findings (PET/MRI) and of coregistration of PET/MRI with subtraction ictal single-photon emission computed tomography (SPECT) coregistered to MRI (SISCOM) (PET/MRI/SISCOM) in localizing the potential epileptogenic zone in patients with drug-resistant epilepsy. We prospectively included 35 consecutive patients with refractory focal epilepsy whose presurgical evaluation included a PET study. Separately acquired PET and structural MRI images were coregistered for each patient. When possible, ictal SPECT and SISCOM were obtained and coregistered with PET/MRI. The potential location of the epileptogenic zone determined by neuroimaging was compared with the seizure onset zone determined by long-term video-EEG monitoring and with invasive EEG studies in patients who were implanted. Structural MRI showed no lesions in 15 patients. In these patients, PET/MRI coregistration showed a hypometabolic area in 12 (80%) patients that was concordant with seizure onset zone on EEG in 9. In 7 patients without MRI lesions, PET/MRI detected a hypometabolism that was undetected on PET alone. SISCOM, obtained in 25 patients, showed an area of hyperperfusion concordant with the seizure onset zone on EEG in 7 (58%) of the 12 of these patients who had normal MRI findings. SISCOM hyperperfusion was less extensive than PET hypometabolism. A total of 19 patients underwent surgery; 11 of these underwent invasive-EEG monitoring and the seizure onset zone was concordant with PET/MRI in all cases. PET/MRI/SISCOM coregistration, performed in 4 of these patients, was concordant in 3 (75%). After epilepsy surgery, 13 (68%) patients are seizure-free after a mean follow-up of 4.5 years. PET/MRI and PET/MRI/SISCOM coregistration are useful for determining the potential epileptogenic zone and thus for planning invasive EEG studies and surgery more precisely, especially in patients without lesions on MRI.

Oxidative stress markers in the neocortex of drug-resistant epilepsy patients submitted to epilepsy surgery

PURPOSEnWhile there is solid experimental evidence of brain oxidative stress in animal models of epilepsy, it has not been thoroughly verified in epileptic human brain. Our purpose was to determine and to compare oxidative stress markers in the neocortex of epileptic and non-epileptic humans, with the final objective of confirming oxidative stress phenomena in human epileptic brain.nnnMETHODSnNeocortical samples from drug-resistant epilepsy patients submitted to epilepsy surgery (n=20) and from control, non-epileptic cortex samples (n=11) obtained from brain bank donors without neurological disease, were studied for oxidative stress markers: levels of reactive oxygen species (ROS), such as superoxide anion (O2(-)); activity of antioxidant enzymes: superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and glutathione reductase (GR); and markers of damage to biomolecules (lipid peroxidation and DNA oxidation).nnnRESULTSnCompared with non-epileptic controls, the neocortex of epileptic patients displayed increased levels of superoxide anion (P≤0.001), catalase (P≤0.01), and DNA oxidation (P≤0.001); a decrease in GPx (P≤0.05), and no differences in SOD, GR and lipid peroxidation.nnnCONCLUSIONSnOur findings in humans are in agreement with those found in animal models, supporting oxidative stress as a relevant mechanism also in human epilepsy. The concurrent increase in catalase and decrease in GPx, together with unchanged SOD levels, suggests catalase as the main antioxidant enzyme in human epileptic neocortex. The substantial increase in the levels of O2(-) and 8-oxo-dG in epileptic patients supports a connection between chronic seizures and ROS-mediated neural damage.

Cannabis use in Spanish patients with multiple sclerosis: Fulfilment of patients' expectations?

OBJECTIVEnMedicinal use of cannabis in chronic neurological diseases is a controversial topic of medical research and the subject of intense public debate. The aim of the study was to evaluate the prevalence of cannabis use, related factors, and degree of satisfaction in Spanish patients with multiple sclerosis (MS) prior to the establishment of medically supervised use.nnnMETHODSnCross-sectional, questionnaire-based survey provided during routine medical visits to consecutive patients in two university-based neurology clinics.nnnRESULTSnThe questionnaire was returned by 175 MS patients (94.1% response rate). The prevalence of ever-use and medicinal cannabis use were 43% and 17.1%, respectively. At the time of the survey, cannabis was being used by 12.5% (5/45) of recreational and 56.7% (17/30) of medical users (p<0.001). First cannabis consumption was after MS onset in 15 (50%) medicinal users. Clinical improvement was reported by 14 (46.7%) medicinal users. Smoking use, awareness of cannabis potential benefits, pain, higher disability, and lower age were independently associated with the medicinal use of cannabis. Most patients would support a future legalisation of cannabis for the control of their symptoms and were willing to receive cannabis under medical control once legalised (83.4% of never-users, 94.5% of ever-users, p<0.05).nnnCONCLUSIONnAlmost half of our MS patients had tried cannabis at some time. However, medicinal use was low and clinical improvement after cannabis use was only reported by a subset of patients. Overall, MS patients were highly motivated for a future medically controlled use.

Presurgical evaluation and cognitive functional reorganization in Fishman syndrome.

Fishman syndrome, also known as encephalocraniocutaneous lipomatosis (ECCL), is a rare, congenital neurocutaneous syndrome characterized by unilateral skin, eye, and brain abnormalities. Epileptic seizures and developmental delay are usually present. We report the clinical, radiological, and, for the first time, neurophysiological findings in a 24-year-old woman diagnosed with ECCL who was evaluated for epilepsy surgery. Functional magnetic resonance imaging revealed transfer of memory and language functions to the nonaffected hemisphere, providing evidence that functional reorganization and restoration of cognitive functions may occur in the context of extensive malformations, such as neurocutaneous syndromes.

Epilepsy surgery in drug resistant temporal lobe epilepsy associated with neuronal antibodies

We assessed the outcome of patients with drug resistant epilepsy and neuronal antibodies who underwent epilepsy surgery. Retrospective study, information collected with a questionnaire sent to epilepsy surgery centers. Thirteen patients identified, with antibodies to GAD (8), Ma2 (2), Hu (1), LGI1 (1) or CASPR2 (1). Mean age at seizure onset: 23 years. Five patients had an encephalitic phase. Three had testicular tumors and five had autoimmune diseases. All had drug resistant temporal lobe epilepsy (median: 20 seizures/month). MRI showed unilateral temporal lobe abnormalities (mainly hippocampal sclerosis) in 9 patients, bilateral abnormalities in 3, and was normal in 1. Surgical procedures included anteromesial temporal lobectomy (10 patients), selective amygdalohippocampectomy (1), temporal pole resection (1) and radiofrequency ablation of mesial structures (1). Perivascular lymphocytic infiltrates were seen in 7/12 patients. One year outcome available in all patients, at 3 years in 9. At last visit 5/13 patients (38.5%) (with Ma2, Hu, LGI1, and 2 GAD antibodies) were in Engels classes I or II. Epilepsy surgery may be an option for patients with drug resistant seizures associated with neuronal antibodies. Outcome seems to be worse than that expected in other etiologies, even in the presence of unilateral HS. Intracranial EEG may be required in some patients.

Identifying the cortical substrates of interictal epileptiform activity in patients with extratemporal epilepsy: An EEG‐fMRI sequential analysis and FDG‐PET study

The aim of this study was to apply sequential analysis of electroencephalography–functional magnetic resonance imaging (EEG‐fMRI) data to study the cortical substrates related to the generation of the interictal epileptiform activity (IEA) in patients with pharmacoresistant extratemporal epilepsy.

Eicosanoid levels in the neocortex of drug-resistant epileptic patients submitted to epilepsy surgery

There is an increasing body of evidence implicating eicosanoids (arachidonic acid metabolites) in the experimental generation of epileptic seizures and the development of epilepsy. Our purpose was to measure the synthesis of eicosanoids from the cyclooxygenase and lipoxygenase pathways in human brain neocortex tissue samples obtained from epileptic patients, and to compare them with non-epileptic control subjects. Epileptic neocortex specimens demonstrated a significant increase (P<0.001) in the levels of three eicosanoids derived from the cyclooxygenase pathway: Prostaglandin E(2) (PGE(2)), Thromboxane A(2) (TXA(2)), and Prostacyclin (PGI(2)), compared to controls. In the epileptic samples the level of TXA(2) was twice as much the levels of PGI(2), while in the control samples the levels of PGI(2) were slightly higher than TXA(2). Conversely, there were no detectable levels of eicosanoids derived from the lipoxygenase pathway: Leukotriene B(4) (LTB(4)) and Leukotriene C(4) (LTC(4)). The lack of leukotrienes synthesis illustrates that COX pathway is dominant in neocortex of epileptic patients. Our human data are consistent with the results obtained in experimental animal models of epilepsy. The important increase in PGE(2) and TXA(2) suggests that selective inhibition of prostanoid synthesis or blockage of prostanoid receptors might provide novel antiepileptic strategies in human epilepsy.