Bayesian EEG source localization using a structured sparsity prior.

This paper deals with EEG source localization. The aim is to perform spatially coherent focal localization and recover temporal EEG waveforms, which can be useful in certain clinical applications. A new hierarchical Bayesian model is proposed with a multivariate Bernoulli Laplacian structured sparsity prior for brain activity. This distribution approximates a mixed ℓ20 pseudo norm regularization in a Bayesian framework. A partially collapsed Gibbs sampler is proposed to draw samples asymptotically distributed according to the posterior of the proposed Bayesian model. The generated samples are used to estimate the brain activity and the model hyperparameters jointly in an unsupervised framework. Two different kinds of Metropolis-Hastings moves are introduced to accelerate the convergence of the Gibbs sampler. The first move is based on multiple dipole shifts within each MCMC chain, whereas the second exploits proposals associated with different MCMC chains. Experiments with focal synthetic data shows that the proposed algorithm is more robust and has a higher recovery rate than the weighted ℓ21 mixed norm regularization. Using real data, the proposed algorithm finds sources that are spatially coherent with state of the art methods, namely a multiple sparse prior approach and the Champagne algorithm. In addition, the method estimates waveforms showing peaks at meaningful timestamps. This information can be valuable for activity spread characterization.

[Faciobrachial dystonic seizures. Semiologic diagnosis in limbic encephalitis]. / Crisis distónicas faciobraquiales. Diagnóstico semiológico en la encefalitis límbica.

Limbic encephalitis (LE) associated with positive potassium channel complex antibodies often manifests with faciobrachial dystonic seizures (FBDS). We retrospectively analyze two cases, admitted to our video-EEG unit between 2006 and 2014. Both patients were males, aged 66 and 76 years respectively, presenting with brief, but very frequent uni/bilateral dystonic brachial movements, hand posturing and ipsilateral facial grimacing. Severe hyponatremia was found in both patients who went on to develop cognitive impairment. Immunosuppressive therapy improved both seizures and cognitive dysfunction. Serology testing confirmed anti VGKC antibody presence. FBDS are often the first manifestation of LE associated to positive anti VGKC antibodies, and are refractory to treatment with antiepileptic drugs. Early diagnosis and treatment of FBDS with immunosuppressive therapy is important, not only because of seizure suppression, but also because it may help limit the extent of the cognitive damage.

Intracranial video-EEG and surgery for focal atonic seizures.

Atonic seizures are epileptic attacks characterised by a sudden loss or diminution of muscle tone. Structures corresponding to inhibitory cortical areas, such as the primary negative motor area or the supplementary negative motor area, could be responsible. We present findings observed in a patient with atonic seizures due to focal epilepsy, who underwent intracranial video-EEG monitoring and epilepsy surgery, and discuss possible underlying mechanisms. [Published with video sequences].

Creutzfeldt-Jakob disease surveillance in Argentina, 1997-2008.

BACKGROUND: Epidemiological data on Creutzfeldt-Jakob disease (CJD) from Latin America are limited. We present a comprehensive epidemiological survey on CJD patients in Argentina based on systematic surveillance between 1997 and 2008. METHODS: A CJD Surveillance Referral Center (SRC) was established in Argentina in 1997; previously a Neuropathology Referral Center was used from 1983 to 1996. All suspected cases referred to the SRC were classified using established criteria on the basis of information derived from the following: clinical data form, EEG, MRI (both for central review), cerebrospinal fluid (CSF) for protein 14-3-3 Western blot (WB), autopsy or biopsy material for neuropathology, prion protein (PrP) immunohistochemistry and PrP WB, as well as blood for DNA studies (when brain tissue was not available). RESULTS: Of the 517 patients referred to the SRC between 1997 and 2008, 211 (40.8%) had CJD or other transmissible spongiform encephalopathies (TSEs) (definite or probable). Possible cases totaled 14.5%, while cases with no WHO criteria accounted for 16.4%. Non-CJD cases excluded by biopsy/autopsy or during follow-up corresponded to 28.2% of the 517 referrals. Main differential diagnoses included neurodegenerative diseases such as Alzheimer's disease, frontotemporal dementia, vascular, metabolic or viral encephalopathy, and Hashimoto's disease. Five percent of referred patients ultimately recovered. Eighty-three percent of TSE cases were sporadic CJD; 17% were genetic, mainly E200K (15.6%); the remaining 1.4% included an octarepeat insertion and two Gerstmann-Sträussler-Scheinker cases (P102L). Seventy-four of 100 definite cases had frozen tissue available for molecular subtyping (PrP(Sc)/codon 129). CSF protein 14-3-3 WB sensitivity was 72.3% and specificity was 92.1%. Clinical diagnostic criteria for probable CJD when compared to definite diagnosis by neuropathology showed 71.3% sensitivity, 86.2% specificity, 94.4% positive predictive value and 48% negative predictive value. Country incidence increased over time and reached 0.85 cases per million in 2008, with the highest rate detected in the city of Buenos Aires (1.8). Districts with 6% of the total population have never reported suspected cases. CONCLUSION: In spite of an increase in incidence observed over time, the difference between Buenos Aires city, where the incidence is comparable to that of smaller European countries with higher population density, and the incidence observed in the rest of the country suggests underreporting in nonmetropolitan areas, probably due to a lack of access to specialized medical facilities. CSF WB sensitivity results for protein 14-3-3 were probably linked to the fact that testing was not routinely repeated during the course of the disease, when earlier test results had been negative. The spectrum of molecular CJD subtypes observed did not differ from other countries in Europe. No iatrogenic or variant CJD cases were identified. The sensitivity and negative predictive value of clinical diagnostic criteria for probable CJD (which includes EEG and/or CSF protein 14-3-3 levels) may have been resulted from confirmed cases not meeting probable criteria before autopsy, due to a lack of ancillary tests such as EEG and/or CSF 14-3-3 WB, or because negative tests were not repeated during follow-up.

A quadratic linear-parabolic model-based EEG classification to detect epileptic seizures.

The two-point central difference is a common algorithm in biological signal processing and is particularly useful in analyzing physiological signals. In this paper, we develop a model-based classification method to detect epileptic seizures that relies on this algorithm to filter electroencephalogram (EEG) signals. The underlying idea was to design an EEG filter that enhances the waveform of epileptic signals. The filtered signal was fitted to a quadratic linear-parabolic model using the curve fitting technique. The model fitting was assessed using four statistical parameters, which were used as classification features with a random forest algorithm to discriminate seizure and non-seizure events. The proposed method was applied to 66 epochs from the Children Hospital Boston database. Results showed that the method achieved fast and accurate detection of epileptic seizures, with a 92% sensitivity, 96% specificity, and 94.1% accuracy.

[Mycoplasma pneumoniae meningoencephalitis in a young adult]. / Meningoencefalitis por Mycoplasma pneumoniae en un adulto joven.

Mycoplasma pneumoniae infections have extrapulmonary complications that involve the nervous system. The neurologic manifestations are diverse. Although the prognosis is usually favorable, the patients can undergo severe permanent sequelae. We present a young female adult with acute meningoencephalitis as a complication of a lower respiratory infection, which followed a benign course without neurologic sequelae.

Single-dose oral lacosamide in refractory simple partial status epilepticus: case report and review.

OBJECTIVES: This study aimed to present 2 patients with simple partial refractory status epilepticus (RSE) treated with a single oral lacosamide (LCM) dose and to review the literature on this topic. METHOD: A retrospective description of 2 patients with simple partial RSE treated with 300 mg of LCM per os (p.o.) and a literature review were done. RESULTS: Both patients responded to single-dose oral LCM treatment with seizure cessation after 30 minutes. CONCLUSIONS: This is the first report on successful treatment of simple partial RSE with a single-dose of LCM p.o.. Oral LCM might represent an option for treatment of patients presenting with simple partial RSE.

Epilepsy surgery in Argentina: long-term results in a comprehensive epilepsy centre.

RATIONALE: Epilepsy surgery procedures started in Argentina more than 50 years ago. This is the first comprehensive and systematic survey of epilepsy surgery long-term outcome from our country. METHODS: A descriptive cohort study was conducted between 1998 and 2008 for drug-resistant epilepsy surgery with a minimum of 12 months follow-up (n=110). In 84 cases (76.36%) resective surgery was performed, and outcome periodically assessed using the Engel score. Patients were stratified into groups: 12, 13-36, 37-60 and over than 60 months of follow-up. Video-EEG with and without intracranial electrode implants, intraoperative electrocorticograms, Wada tests, pathology reports, use of antiepileptic drugs (AEDs), and surgical complication rates were evaluated. RESULTS: Surgical techniques included: 69 lobectomies (62.7%), 15 lesionectomies (13.6%), 6 callosotomies (5.4%), 6 multiple subpial transection (5.4%), 11 vagus nerve stimulations (10%), 3 hemispherectomies (2.7%). Male: female ratio: 1/1.44. Mean age at time of surgery: 26.2 years. Mean duration of epilepsy: 14 years. Age at seizure onset: 11.5 years. Mean follow-up: 46 months. Pathology findings: mesial temporal sclerosis 32 (35.1%); dual pathology 17 (18.7%); cortical dysplasia 15 (16.4%); non-specific inflammatory changes 11 (12.1%); tumors 7 (7.7%); other 6 (6.8%). Engel scores at 12 months follow-up: 72.6% (61) class I, 16.6% (14) class II and 15.5% (13) class III-IV; 13-36 months after surgery: 68.1% of cases were class I, 15.9% class II and 15.5% class III-IV. After 37-60 months, 74% class I, 14% class II, 14% class III-IV. Over 60 months (n=45) 78% class I, 13.5% class II and 8.1% class III-IV. CONCLUSION: Conducting a successful epilepsy surgery program in a developing country is challenging. These results should encourage specialists in these countries. Long-term outcome results comparable to centres in developed countries can be achieved.

ABC transporters during epilepsy and mechanisms underlying multidrug resistance in refractory epilepsy.

It is estimated 20-25% of the epileptic patients fails to achieve good control with the different antiepileptic drugs (AEDs) treatments, developing refractory epilepsy (RE). Discovered first in cancer, the activity of P-glycoprotein (P-gp) and others ABC transporters as multidrug-resistance-associated proteins (MRPs) and breast cancer resistant protein (BCRP) are directly related with the refractoriness. We have observed the overexpression of these all transporters in the brain of patients with RE, and according with other authors, all these data suggests an active drug efflux from brain. Both constitutive and seizure induced brain P-gp overexpression was also suggested. As confirmation of these clinical evidences, different models of experimental epilepsy have demonstrated P-gp overexpression on blood brain barrier (BBB) and brain parenchyma cells, as astrocytes and neurons. In our model, early P-pg detection in vessel-related cells and later additional P-gp detection in neurons, correlated with the gradual loss of protective effect of phenytoin. The progressive neuronal P-gp expression, depending on intensity and time-constancy of seizure-injury, was in agreement with the development of "P-gp-positive seizure-axis" proposed by Kwan & Brodie, who also showed that the development of RE directly correlated with the number and frequency of seizures before initiation of drug therapy. P-gp expression in excretory organs suggests that P-gp have a central role in drug elimination. Persistent low levels of AEDs in plasma and P-gp brain overexpression in several RE pediatric patients were reported. We also observed in adult RE patients, an increased liver clearance of 99mTc-hexakis-2-methoxyisobutylisonitrile (99mTc-MIBI) (a P-gp substrate), and the surgically treated cases showed P-gp brain overexpression. These results suggest the systemic hyperactivity of P-gp in RE patients, including brain P-gp over-expression should be suspected when persistent subtherapeutic levels of AEDs in plasma are detected. P-gp neuronal expression described in both clinical and experimental reports indicates that additional mechanisms could be operative from seizure-affected P-gp-positive neurons, due to AEDs targets are expressed at membrane level. An alternative mechanism was demonstrated in P-gp-expressed cells that exhibit lower membrane potential (Deltapsi(0)=-10 to -20) compared to normal physiological Deltapsi(0) of -60 mV. Under this situation and irrespective to the P-gp pharmacoresistant property or type of drug treatment selected, P-gp-expressed neurons could increase their sensitivity to new seizures perhaps as an epileptogenic mechanism. The understanding of properties of these ABC transporters can offer new tools for better selection of more effective preventive or therapeutic strategies and avoid the invasive surgical treatments for RE.

Malformación del desarrollo cortical: nuestra experiencia acerca de 150 casos / Cortical development malformations (CDM): our experience on 150 cases

Objetivo Realizar una evaluación retrospectiva de 150 pacientes de una serie de 570 (26.3%), operados por epilepsia refractaria con diagnóstico de algún tipo de malformación del desarrollo cortical (MDC), desde 1988 a noviembre de 2009. Material y método. 118 niños y 32 adultos; 69 localización temporal (42 niños, 27 adultos) y 81 extratemporal (76 niños y 5 adultos). La evaluación prequirúrgica incluye: características clínico-semiológicas de las crisis epilépticas, EEG de superficie, video EEG, TC y/o RM y evaluación neuropsicológica. Población: varones: 86; mujeres 64; edad, media de 6.7 años (rango: 6 m – 18.9 a) en los niños y media de 31.3 años (rango: 19-59 a) en los adultos. Evolución de epilepsia: media de 4.9 años para los niños (rango: 1 mes a 17 años) y media de 13.8 (rango: 2 meses a 50 años). Aspectos clínicos: tipos de crisis: pudiendo un mismo paciente presentar más de una de ellas, vinculadas a la localización, CPS, ausencias, crisis tónicas, automatismos, crisis versivas, CPC, anopsia transitoria, “drop attacks”, “Startle epilepsia”, escotoma, automatismos masticatorios, crisis clónicas, fotopsia, desviación ocular, “head attacks”. Imágenes: la TC fue normal en 5, y se realizó IRM en todos a partir de 1996

Objective: To evaluate the surgical results in a group of patients with epilepsy associated with cortical development malformations (CDM). Method: A retrospective study in 150 patients of a series of 570 patients (26.3%) who have undergone surgery for intractable epilepsy with a diagnosis of CDM, since 1988. Clinical features,scalp EEG, video EEG, CT scan, MRI and neuropsychological evaluation were assessed. Population: males: 86 patients, females: 64; mean age, children: 6.7 years (range: 0,5-18.9) and adults: 31.3 years (range: 19-59); mean evolution of epilepsy, children: 4.9 years (range: 1mo-17 yr.), adults: 13.8 years (range: 2mo-50 yr.). Clinical manifestations: CPS, absences,tonic crises, automatisms and versive crises, CPS, transitory anopsia, drop attacks and Startle epilepsy, scotoma, masticatory automatisms, clonic crises, photopsia, eye deviation and head attacks. Imaging: CT scan was normal in 5, and MRI was performed since 1996. Twenty of 150 (13.3%) required chronic intracranial electrodes implantation. Surgical procedures: resectives: lesionectomies 63 (wide lesionectomy, 17 and + MST, 5), standard anterior temporal lobectomies (SATL) 37, anteromesial resections (Spencer) 9, corticectomies 11(+MST, 1),amigdalo- hippocampectomies 3, anatomic hemispherectomy 1, lobectomy1 and polectomies 4; disconnecting procedures: functional hemispherectomies (FH) 10, hemispherotomy 4, hemi-hemispherectomy 1, multiple subpial transection (MST) 1 and 2 callosotomies...

Oxcarbazepine in pregnancy: clinical experience in Argentina.

The potential teratogenicity of antiepileptic drugs (AEDs) is a major concern for women with epilepsy who are considering pregnancy. Traditional AEDs are associated with an at least twofold risk of fetal malformations compared with the general population. The risk of malformations with newer AEDs is unclear. This article reports the multicenter clinical experience in Argentina of pregnant women with epilepsy receiving AEDs. Of 114 pregnancies monitored, 16 newborns had anomalies: 3 cardiac, 3 skull, and 2 gastrointestinal malformations, and 8 facial dysmorphies. Most fetal anomalies were observed following exposure to phenobarbital, valproate, and carbamazepine. Of 55 babies exposed to the new-generation AED oxcarbazepine (20 as combination therapy and 35 as monotherapy), one malformation (cardiac) was reported (in a patient receiving oxcarbazepine and phenobarbital). Thus, newer AEDs may have a lower teratogenic risk than traditional AEDs. These data add to the growing experience with AED therapy in pregnant women with epilepsy.