Antonio Donaire

Cognitive disorders associated with epilepsy: diagnosis and treatment.

Introduction:Cognitive disorders are common in patients with epilepsy. Their aetiology is multifactorial, being affected by the type and location of the epileptogenic lesion, epileptic syndrome, type of seizures, age of onset, frequency and severity. Timely diagnosis and treatment can help to reduce their impact on the patients quality of life. Results:The most significant cognitive deficits are associated with focal epilepsy, although some, usually mild, neuropsychological disorders can be found in idiopathic generalized epilepsy. The use of antiepileptic drugs (AEDs) can cause additional neuropsychological disorders that are of particular concern in learning-age children and elderly patients with cognitive disorders before the start of treatment. Recent studies have raised the concern that the use of some AEDs during pregnancy may cause cognitive disorders in the child exposed to them in utero. Cognitive disorders can also present as a complication of surgery for refractory epilepsy. Some risk factors for significant memory loss after surgery for temporal lobe epilepsy have been described. They include intervention in the dominant hemisphere, good preoperative function and poor functional reserve in the contralateral hippocampus. Conclusions:The heterogeneity of different types of epilepsy makes case–control studies difficult; however, thanks to the growing interest in the neuropsychological deficits associated with epilepsy, we now know some factors that could lead to the appearance of these disorders and their prognosis. Special care must be taken to detect cognitive side effects associated with AEDs, which seem to be more common with classic than with new AEDs, and in those patients receiving polytherapy. Neuropsychological assessment should be routinely performed before epilepsy surgery to predict possible postsurgical cognitive deficits.

Cortical laminar necrosis related to prolonged focal status epilepticus

Cortical laminar necrosis (CLN) is radiologically defined as high intensity cortical lesions on T1 weighted MRI images following a gyral distribution. Histopathologically, CLN is characterised by pannecrosis of the cortex involving neurones, glial cells, and blood vessels. It has been reported to be associated with hypoxia, metabolic disturbances, drugs, and infections. We present two patients who developed CLN and permanent neurological deficits after prolonged and repeated focal status epilepticus. The possible mechanisms leading to CLN in these patients are discussed, together with the implications of prompt and aggressive treatment in similar cases.

Differential vulnerability of gray matter and white matter to intrauterine growth restriction in preterm infants at 12 months corrected age.

Intrauterine growth restriction (IUGR) is associated with a high risk of abnormal neurodevelopment. Underlying neuroanatomical substrates are partially documented. We hypothesized that at 12 months preterm infants would evidence specific white-matter microstructure alterations and gray-matter differences induced by severe IUGR. Twenty preterm infants with IUGR (26-34 weeks of gestation) were compared with 20 term-born infants and 20 appropriate for gestational age preterm infants of similar gestational age. Preterm groups showed no evidence of brain abnormalities. At 12 months, infants were scanned sleeping naturally. Gray-matter volumes were studied with voxel-based morphometry. White-matter microstructure was examined using tract-based spatial statistics. The relationship between diffusivity indices in white matter, gray matter volumes, and perinatal data was also investigated. Gray-matter decrements attributable to IUGR comprised amygdala, basal ganglia, thalamus and insula bilaterally, left occipital and parietal lobes, and right perirolandic area. Gray-matter volumes positively correlated with birth weight exclusively. Preterm infants had reduced FA in the corpus callosum, and increased FA in the anterior corona radiata. Additionally, IUGR infants had increased FA in the forceps minor, internal and external capsules, uncinate and fronto-occipital white matter tracts. Increased axial diffusivity was observed in several white matter tracts. Fractional anisotropy positively correlated with birth weight and gestational age at birth. These data suggest that IUGR differentially affects gray and white matter development preferentially affecting gray matter. At 12 months IUGR is associated with a specific set of structural gray-matter decrements. White matter follows an unusual developmental pattern, and is apparently affected by IUGR and prematurity combined.

Validation of FDG‐PET/MRI coregistration in nonlesional refractory childhood epilepsy

Purpose:  To validate the use of 18F‐fluorodeoxyglucose–positron emission tomography/magnetic resonance imaging (FDG‐PET/MRI) coregistration for epileptogenic zone detection in children with MRI nonlesional refractory epilepsy and to assess its ability to guide a second interpretation of the MRI studies.

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

PURPOSE To assess the ability of neuropsychological tests to determine the side of seizure onset for preoperative assessment in patients with drug-resistant temporal lobe epilepsy. METHODS Twenty-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). RESULTS Memory 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. CONCLUSIONS Language 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.

Identifying the structures involved in seizure generation using sequential analysis of ictal-fMRI data.

UNLABELLED The aim of this study was to investigate if sequential analysis of BOLD signal changes induced by seizures is useful for preoperative identification of the site of seizure onset in patients with pharmaco-resistant focal epilepsy. METHOD We analyzed BOLD raw data from 5 patients with focal medically refractory epilepsy who experienced partial seizures during fMRI as part of a preoperative evaluation. To sequence the changes in BOLD signal seizure-induced, each seizure epoch was divided into groups of five consecutive images (ten-second blocks). t-maps were calculated continuously from 120 s before the onset of clinical/EEG seizure onwards by comparing two consecutive groups of five images. Time lag between each comparison was 2 s. Relative changes in BOLD signal between two consecutive groups of five images along the seizure epoch were determined. Results were compared with those of subtraction ictal SPECT coregistered with MRI (SISCOM) and intracranial EEG (2 patients). RESULTS A typical seizure was registered in each patient. After sequential analysis, a well-localized and statistically significant (t: 7-14) area of signal increase was consistently found at seizure initiation in each patient. This area invariably preceded the onset of clinical/electrical seizure by several seconds (6-52 s); was concordant with SISCOM results in all but one patient; and overlapped with the ictal onset zone determined by intracranial EEG in those 2 patients who underwent invasive-EEG recordings. Complete resection of this initial area of signal increase resulted in seizure remission. Three out of four patients who underwent epilepsy surgery remained seizure-free. CONCLUSION Sequential analysis of ictal-fMRI data may be useful to precisely and non-invasively delineate the ictal onset zone within the brain; and provide insights into the cerebral substrates involved in the generation and propagation of seizures.

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.

Prevalence of interictal psychiatric disorders in patients with refractory temporal and extratemporal lobe epilepsy in Spain. A comparative study.

We aim to investigate whether temporal origin of epilepsy increases the risk of developing a psychiatric disorder and more specifically a major depressive disorder. The lack of standardized diagnostic instruments and the methodologic differences between studies highlight the fact that this issue warrants further, systematic, study. Three‐hundred eight patients with complex partial seizures were classified according to temporal or extratemporal origin, following the Commission on Classification and Terminology of the International League Against Epilepsy (ILAE), 1989 localization‐related concept. All patients were assessed using the Structured Interview for DSM‐IV axis I psychiatric disorders (SCID‐I). Lifetime and previous‐year prevalence of psychiatric disorders were compared in temporal and extratemporal subgroups, using multivariate analysis. Previous‐year major depression was significantly associated with temporal lobe origin. Our results do not support the hypothesis that patients with temporal lobe epilepsy (TLE) have more psychiatric illness in general, although they do suggest a specific connection between TLE and major depression.

Validation of the Spanish version of the Liverpool Adverse Events Profile in patients with epilepsy

The objective of the study was to validate the Spanish version of the Liverpool Adverse Events Profile (LAEP). An observational, cross-sectional, multicenter study was carried out on patients with epilepsy treated with a stable dose of antiepileptic drugs. Patients completed the LAEP, Quality of Life in Epilepsy Inventory-31 (QOLIE-31), and Hospital Anxiety and Depression Scale (HADS). Two hundred sixty-six patients were recruited. The LAEP was completed in a short time, perceived as easy to complete, and there was no relevant information missing. Ceiling/floor effects were negligible. Internal consistency (Cronbachs alpha=0.84) and test-retest reliability (ICC=0.81) were satisfactory. LAEP scores consistently correlated with QOLIE-31 (r=0.71) and HADS (r=0.52-0.63) scores. When the LAEP was used to discriminate between patients with and without adverse events, the scores on the QOLIE and HADS corresponded. The Spanish version of the LAEP scale exhibits adequate psychometric properties, suggesting that it is an appropriate instrument to measure adverse events among Spanish-speaking patients with epilepsy.

Postictal psychosis: A retrospective study in patients with refractory temporal lobe epilepsy

UNLABELLED Postictal psychosis (PIP) represents 25% of the psychoses seen in epileptic patients. A high frequency of bilateral independent epileptiform activity has been observed in patients with PIP. The objective of this study was to determine the frequency of PIP in patients with temporal lobe epilepsy (TLE) who underwent video-EEG monitoring and to investigate possible differences between PIP and control patients. METHODS Clinical, electroencephalographic and neuroimaging data of 5 PIP patients with TLE were compared with data of 50 patients with TLE without psychotic antecedents. Patients with a past history of interictal psychosis were excluded. RESULTS From 55 patients, 5 were patients with PIP and 50 controls. 31 (62%) were men, 9 (16.4%) had a previous history of encephalitis and 6 (10.9%) of status epilepticus. The mean age was 42.2 years (S.D. 12.93). Mean age at epilepsy onset was 16.95 years (S.D. 12.93) and mean seizure frequency 5seizures/month (S.D. 1.87). The frequency of PIP was 5/55 (9.1%). Previous history of status epilepticus was more frequent in PIP patients than in controls (p: 0.019). PIP patients more frequently had a non-lateralizing ictal EEG than controls (p: 0.001). Bitemporal lobe dysfunction revealed by neuropsychological studies was greater than expected by the observed lesion on MRI studies in patients with PIP. Moreover, the presurgical study was less conclusive in PIP than in control patients (p: 0.049). CONCLUSIONS PIP is observed in up to 9% of patients with TLE undergoing video-EEG monitoring and most often develops in patients with bitemporal lobe dysfunction.