GABAergic Neuron Deficit As An Idiopathic Generalized Epilepsy Mechanism: The Role Of BRD2 Haploinsufficiency In Juvenile Myoclonic Epilepsy

Idiopathic generalized epilepsy (IGE) syndromes represent about 30% of all epilepsies. They have strong, but elusive, genetic components and sex-specific seizure expression. Multiple linkage and population association studies have connected the bromodomain-containing gene BRD2 to forms of IGE. In mice, a null mutation at the homologous Brd2 locus results in embryonic lethality while heterozygous Brd2+/− mice are viable and overtly normal. However, using the flurothyl model, we now show, that compared to the Brd2+/+ littermates, Brd2+/− males have a decreased clonic, and females a decreased tonic-clonic, seizure threshold. Additionally, long-term EEG/video recordings captured spontaneous seizures in three out of five recorded Brd2+/− female mice. Anatomical analysis of specific regions of the brain further revealed significant differences in Brd2+/− vs +/+ mice. Specifically, there were decreases in the numbers of GABAergic (parvalbumin- or GAD67-immunopositive) neurons along the basal ganglia pathway, i.e., in the neocortex and striatum of Brd2+/− mice, compared to Brd2+/+ mice. There were also fewer GABAergic neurons in the substantia nigra reticulata (SNR), yet there was a minor, possibly compensatory increase in the GABA producing enzyme GAD67 in these SNR cells. Further, GAD67 expression in the superior colliculus and ventral medial thalamic nucleus, the main SNR outputs, was significantly decreased in Brd2+/− mice, further supporting GABA downregulation. Our data show that the non-channel-encoding, developmentally critical Brd2 gene is associated with i) sex-specific increases in seizure susceptibility, ii) the development of spontaneous seizures, and iii) seizure-related anatomical changes in the GABA system, supporting BRD2's involvement in human IGE

Perception and Attitude towards Stroke by Professionals of Emergency Medical Service in an Urban City in Southeastern Brazil

Introduction: Stroke awareness by lay people in general is poor. It has been estimated that only as much as one third of patients with acute stroke reach emergency medical services within two hours of onset of their symptoms. We aimed to assess perception of and attitude towards a person with an acute stroke by professionals working in mobile unit of emergency medical service in the city of Campinas, Brazil. Material and Methods: The study was conducted during VII Stroke Workshop of Campinas in November 2007. We used an anonymous self-report questionnaire with a clinical case of an acute stroke with duration of 50 minutes. We asked two open-ended questions to gauge perception and attitude. Results: One-hundred forty-nine of 205 (73%) participants answered the questionnaire; 49% were women, average age of 37 years (range 21-59). Ninety (60%) were professionals allied to medicine (nurses, health auxiliary, dentists), six (4%) were physicians, and 53 (36%) were other professionals (secretary, driver). In regard to perception, 142 of 149 (95%) had a correct perception of stroke. In regard to attitude, in general, the basic support measures have been pointed out, but only one (0.5%) mentioned an issue of time less than 3 hours for thrombolysis, four (2%) mentioned the possibility of thrombolysis, and 12 (8%) requested computed tomographic examination. Discussion: It appears that professionals allied to medicine can diagnosis stroke of anterior circulation; however, they do not have thrombolytic therapy in mind, and this should be considered the default treatment for all patients with stroke within the "therapeutic window."18319519

Texture analysis of magnetic resonance images of patients with juvenile myoclonic epilepsy

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Background/purpose: Juvenile myoclonic epilepsy (JME) is the most frequent subsyndrome of the idiopathic generalized epilepsies, and experimental investigations support that the thalamus is a key structure in the mechanisms of JME. Texture analysis (TA) is an image processing technique which can be used to characterize images such as MRI. Objective: The goal of this work was to investigate the thalamus of patients with JME using TA, a quantitative neuroimaging technique. Methods: Patients and controls were submitted to MRI investigation. Images were acquired in a 2-Tesla scanner. The T1 volumetric sequence was used for thalamic segmentation and extraction of texture parameters. Twenty-four patients with a diagnosis of JME and 20 healthy volunteers were investigated. Results: Texture analysis revealed differences between the right thalamus of patients and controls. Conclusions: The present investigation supports the participation of the thalamus in the disease mechanisms of JME. Texture analysis may be a useful tool in the quantitative neuroimaging investigation of the epilepsies and can be important to understand JME. (C) 2012 Elsevier Inc. All rights reserved.2712228Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

VI. Indtægt og Alder

Purpose: Clobazam (CLB) has an important antiepileptic effect and is less expensive than the new antiepileptic drugs (AEDs), but still has not been considered as first-line drug in the treatment of epilepsy. We evaluated the efficacy of CLB as add-on therapy in patients with refractory partial epilepsy. Methods: This was an open, retrospective study, conducted at the epilepsy clinic of our university hospital. All patients had chronic epilepsy and were being evaluated for epilepsy surgery. CLB was introduced as add-on therapy (starting with 10 mg/ day) in patients with previous failure of at least two AEDs. Information was obtained from clinical notes and follow-up visits. Results: We evaluated 97 patients, 37 men and 60 women. Ages ranged from 15 to 70 years (mean, 35.8 years). Etiology of epilepsy was hippocampal atrophy in 67 (69%), cortical dysgenesis in nine (9.3%), and other etiologies in nine (9.3%). In 12 (12.3%) patients, the etiology of epilepsy was not identified despite clinical and neurologic investigation. Patients used CLB for a period ranging from 1 month to 7 years and 9 months (mean, 16.7 months) with doses ranging from 10 to 60 mg/day (mean, 29.7 mg/day). Seven (7.2%) patients were seizure free, 48 (49.4%) had greater than or equal to 50% of improvement in seizure control, 39 (40.2%) had <50% of improvement in seizure control, and in three (3.1%), no data were available. Conclusions: We conclude that CLB may have efficacy equivalent to that of the new AEDs when used as add-on therapy in patients with refractory epilepsy. CLB should be considered an economic alternative in the treatment of patients with refractory epilepsy.42453954

MRI reveals structural abnormalities in patients with idiopathic generalized epilepsy

Objective: To evaluate MRI findings in a large group of patients with idiopathic generalized epilepsies. Methods: Idiopathic generalized epilepsies were diagnosed according to clinical and EEG criteria following International League Against Epilepsy recommendations. MRI was performed in a 2.0 T scanner using a previously established epilepsy protocol. Images were reviewed, and any abnormality was reported. Patients were divided in those with and without MRI abnormalities. Comparisons were made between these groups concerning age, age at seizure onset, subsyndrome, EEG findings, and seizure control. Results: Of the 134 MRIs evaluated, 33 (24%) showed abnormalities, most of which (88%) were nonspecific. There were eight main abnormalities: arachnoid cyst, diffuse cortical atrophy, basal ganglia abnormalities (signal alterations and prominent perivascular spaces), ventricular abnormalities (uni- or bilateral increased volume of the lateral ventricles), white matter abnormalities (increased T2 signal in the frontal lobes), reduced hippocampal volume, focal gyral abnormality, and area of gliosis in the frontal lobe. Comparisons between the groups showed a higher proportion of EEG focalities in patients with abnormal MRI, which were in most part concordant with the location of the MRI abnormalities. Conclusions: Twenty-four percent of patients with idiopathic generalized epilepsies had MRI abnormalities. However, the majority of these abnormalities were nonspecific.o TEXTO COMPLETO DESTE ARTIGO, ESTARÁ DISPONÍVEL À PARTIR DE AGOSTO DE 2015.67584885

EEG features in idiopathic generalized epilepsy: Clues to diagnosis

Purpose: To investigate the EEG profile and its contribution for diagnosis and management in a group of patients with a clinical diagnosis of idiopathic generalized epilepsy (IGE) who were referred to a tertiary hospital. Methods: We retrospectively studied clinical and EEG features of 180 consecutive patients with IGE. Eighty patients were diagnosed with juvenile myoclonic epilepsy (JME), 35 had absence epilepsy (AE), 13 had generalized tonic-clonic seizures on awakening (GTCS-A), 28 had generalized tonic-clonic seizures only (TCS), and 24 had adult-onset idiopathic generalized epilepsy (AIGE). The EEGs were classified in typical (synchronous generalized spike or polyspikes-and-wave discharges with normal background), atypical (with clear focalities or asymmetries), and normal. Results: The 493 EEG exams were analyzed. The first EEG was normal in 45% of the 180 patients, and only 33% had typical abnormalities. AE had a higher proportion of typical examinations and needed fewer sequential examinations to register a typical abnormality compared with the other groups. By contrast, the serial EEG profile of TCS and AIGE showed a higher proportion of normal and atypical EEG findings. Conclusions: These findings support previous recommendations that IGE patients should be treated with appropriate therapy based on clinical history. Waiting for a typical abnormal EEG pattern can generate an unacceptable delay in the correct diagnosis and treatment of these patients. In patients with long-term epilepsy, the diagnosis may be difficult. Furthermore, serial EEGs can help to elucidate the syndromic diagnosis, especially in patients with TCS and AIGE.47352352

MRI volumetry shows increased anterior thalamic volumes in patients with absence seizures

The interaction between thalamus and cortex appears to be critical to the pathophysiology of idiopathic generalized epilepsies (IGEs). The objective of this study was to investigate thalamic volumes of a group of patients with IGEs using high-resolution MRI. Thalamic segmentation was performed by the same rater, who was unaware of the diagnosis. Thalamic volumes were divided into anterior half and posterior half. One hundred forty-seven patients were scanned (71 with juvenile myoclonic epilepsy, 49 with generalized tonic-clonic seizures only, and 27 with absence epilepsy). Subgroup analyses with corrections for multiple comparisons showed that, when compared with those of controls, anterior thalamic volumes were increased in patients with absence epilepsy and juvenile myoclonic epilepsy with absence seizures, but not in patients with generalized tonic-clonic seizures only and juvenile myoclonic epilepsy without absence seizures. Our results demonstrated that the anterior thalamus is structurally different in patients with IGEs and absence seizures as compared with patients with IGEs without absence seizures. (c) 2006 Elsevier Inc. All rights reserved.8357558