RESUMEN
Idiopathic spinal cord herniation (ISCH) is a rare spinal disease, in which chronic cerebrospinal fluid pulsations push the arachnoid and adjacent thoracic spinal cord region through an antero-lateral dural defect of congenital, post-traumatic, or inflammatory/erosive origin. Symptomatic patients commonly present around the 5th decade of life with slowly progressive myelopathy. Diagnosis relies on high-resolution magnetic resonance imaging. Stable mild cases may be observed, whereas in progressive symptomatic situations, surgical spinal cord reposition and dural defect repair with a dural patch is the preferred treatment. We present a case of ISCH at T5/6 and a review the literature.
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Herniorrafia/métodos , Enfermedades de la Médula Espinal/cirugía , Médula Espinal/cirugía , Vértebras Torácicas/cirugía , Herniorrafia/efectos adversos , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Epilepsy comprises several syndromes, amongst the most common being mesial temporal lobe epilepsy with hippocampal sclerosis. Seizures in mesial temporal lobe epilepsy with hippocampal sclerosis are typically drug-resistant, and mesial temporal lobe epilepsy with hippocampal sclerosis is frequently associated with important co-morbidities, mandating the search for better understanding and treatment. The cause of mesial temporal lobe epilepsy with hippocampal sclerosis is unknown, but there is an association with childhood febrile seizures. Several rarer epilepsies featuring febrile seizures are caused by mutations in SCN1A, which encodes a brain-expressed sodium channel subunit targeted by many anti-epileptic drugs. We undertook a genome-wide association study in 1018 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 7552 control subjects, with validation in an independent sample set comprising 959 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 3591 control subjects. To dissect out variants related to a history of febrile seizures, we tested cases with mesial temporal lobe epilepsy with hippocampal sclerosis with (overall n = 757) and without (overall n = 803) a history of febrile seizures. Meta-analysis revealed a genome-wide significant association for mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures at the sodium channel gene cluster on chromosome 2q24.3 [rs7587026, within an intron of the SCN1A gene, P = 3.36 × 10(-9), odds ratio (A) = 1.42, 95% confidence interval: 1.26-1.59]. In a cohort of 172 individuals with febrile seizures, who did not develop epilepsy during prospective follow-up to age 13 years, and 6456 controls, no association was found for rs7587026 and febrile seizures. These findings suggest SCN1A involvement in a common epilepsy syndrome, give new direction to biological understanding of mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures, and open avenues for investigation of prognostic factors and possible prevention of epilepsy in some children with febrile seizures.
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Epilepsia del Lóbulo Temporal/genética , Mutación/genética , Canal de Sodio Activado por Voltaje NAV1.1/genética , Esclerosis/genética , Convulsiones Febriles/genética , Epilepsia del Lóbulo Temporal/etiología , Estudio de Asociación del Genoma Completo/métodos , Hipocampo/patología , Humanos , Estudios Prospectivos , Convulsiones Febriles/diagnóstico , Lóbulo Temporal/patologíaRESUMEN
Deletions at 16p13.11 are associated with schizophrenia, mental retardation, and most recently idiopathic generalized epilepsy. To evaluate the role of 16p13.11 deletions, as well as other structural variation, in epilepsy disorders, we used genome-wide screens to identify copy number variation in 3812 patients with a diverse spectrum of epilepsy syndromes and in 1299 neurologically-normal controls. Large deletions (> 100 kb) at 16p13.11 were observed in 23 patients, whereas no control had a deletion greater than 16 kb. Patients, even those with identically sized 16p13.11 deletions, presented with highly variable epilepsy phenotypes. For a subset of patients with a 16p13.11 deletion, we show a consistent reduction of expression for included genes, suggesting that haploinsufficiency might contribute to pathogenicity. We also investigated another possible mechanism of pathogenicity by using hybridization-based capture and next-generation sequencing of the homologous chromosome for ten 16p13.11-deletion patients to look for unmasked recessive mutations. Follow-up genotyping of suggestive polymorphisms failed to identify any convincing recessive-acting mutations in the homologous interval corresponding to the deletion. The observation that two of the 16p13.11 deletions were larger than 2 Mb in size led us to screen for other large deletions. We found 12 additional genomic regions harboring deletions > 2 Mb in epilepsy patients, and none in controls. Additional evaluation is needed to characterize the role of these exceedingly large, non-locus-specific deletions in epilepsy. Collectively, these data implicate 16p13.11 and possibly other large deletions as risk factors for a wide range of epilepsy disorders, and they appear to point toward haploinsufficiency as a contributor to the pathogenicity of deletions.
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Cromosomas Humanos Par 16 , Susceptibilidad a Enfermedades , Epilepsia/genética , Mutación , Eliminación de Secuencia , Humanos , Hibridación de Ácido Nucleico/genética , SíndromeRESUMEN
BACKGROUND: In recent years, an increasing number of auto-antibodies (AB) have been detected in the CSF and serum of patients with new onset epilepsy. Some of these patients develop convulsive or nonconvulsive status epilepticus (AB-SE), necessitating intensive medical care and administration of multiple antiepileptic and immunomodulatory treatments of uncertain effectiveness. OBJECTIVES: In this retrospective multicenter survey we aimed to determine the spectrum of gravity, the duration and the prognosis of the disorder. In addition, we sought to identify the antibodies associated with this condition, as well as determine whether there is a most effective treatment regime. METHODS: 12 European Neurology University Clinics, with extensive experience in the treatment of SE patients, were sent a detailed questionnaire regarding symptoms and treatment of AB-SE patients. Seven centers responded positively, providing a total of 13 patients above the age of 16. RESULTS: AB-SE affects mainly women (12/13, 92%) with a variable age at onset (17-69 years, median: 25 years). The duration of the disease is also variable (10 days to 12 years, median: 2 months). Only the 3 oldest patients died (55-69 years). Most patients were diagnosed with anti NMDAR encephalitis (8/13) and had oligoclonal bands in the CSF (9/13). No specific treatment regimen (antiepileptic, immunomodulatory) was found to be clearly superior. Most of the surviving 10 patients (77%) recovered completely or nearly so within 2 years of index poststatus. CONCLUSION: AB-SE is a severe but potentially reversible condition. Long duration does not seem to imply fatal outcome; however, age older than 50 years at time of onset appears to be a risk factor for death. There was no evidence for an optimal antiepileptic or immunomodulatory treatment. A prospective multicenter study is warranted in order to stratify the optimal treatment algorithm, determine clear risk factors of unfavorable outcome and long-term prognosis.
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Autoanticuerpos/inmunología , Convulsiones/inmunología , Estado Epiléptico/inmunología , Adolescente , Adulto , Anciano , Autoanticuerpos/sangre , Autoanticuerpos/líquido cefalorraquídeo , Electroencefalografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Convulsiones/complicaciones , Convulsiones/tratamiento farmacológico , Convulsiones/fisiopatología , Estado Epiléptico/diagnóstico , Estado Epiléptico/tratamiento farmacológico , Estado Epiléptico/fisiopatología , Encuestas y Cuestionarios , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: Alzheimer disease (AD) is characterized by functional impairment in the neural elements and circuits underlying cognitive and memory functions. We hypothesized that fornix/hypothalamus deep brain stimulation (DBS) could modulate neurophysiological activity in these pathological circuits and possibly produce clinical benefits. METHODS: We conducted a phase I trial in 6 patients with mild AD receiving ongoing medication treatment. Patients received continuous stimulation for 12 months. Three main lines of investigation were pursued including: (1) mapping the brain areas whose physiological function was modulated by stimulation using standardized low-resolution electromagnetic tomography, (2) assessing whether DBS could correct the regional alterations in cerebral glucose metabolism in AD using positron emission tomography (PET), and 3) measuring the effects of DBS on cognitive function over time using clinical scales and instruments. RESULTS: DBS drove neural activity in the memory circuit, including the entorhinal, and hippocampal areas and activated the brain's default mode network. PET scans showed an early and striking reversal of the impaired glucose utilization in the temporal and parietal lobes that was maintained after 12 months of continuous stimulation. Evaluation of the Alzheimer's Disease Assessment Scale cognitive subscale and the Mini Mental State Examination suggested possible improvements and/or slowing in the rate of cognitive decline at 6 and 12 months in some patients. There were no serious adverse events. INTERPRETATION: There is an urgent need for novel therapeutic approaches for AD. Modulating pathological brain activity in this illness with DBS merits further investigation.
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Enfermedad de Alzheimer/complicaciones , Encéfalo/fisiología , Estimulación Encefálica Profunda/métodos , Trastornos de la Memoria/etiología , Trastornos de la Memoria/terapia , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/patología , Encéfalo/patología , Mapeo Encefálico , Inhibidores de la Colinesterasa/uso terapéutico , Electroencefalografía/métodos , Femenino , Estudios de Seguimiento , Lóbulo Frontal/fisiología , Hipocampo/fisiología , Humanos , Hipotálamo/fisiología , Imagen por Resonancia Magnética , Masculino , Trastornos de la Memoria/diagnóstico por imagen , Trastornos de la Memoria/patología , Persona de Mediana Edad , Vías Nerviosas/fisiología , Pruebas Neuropsicológicas , Tomografía de Emisión de Positrones/métodos , Escalas de Valoración Psiquiátrica , Factores de TiempoRESUMEN
Partial epilepsies have a substantial heritability. However, the actual genetic causes are largely unknown. In contrast to many other common diseases for which genetic association-studies have successfully revealed common variants associated with disease risk, the role of common variation in partial epilepsies has not yet been explored in a well-powered study. We undertook a genome-wide association-study to identify common variants which influence risk for epilepsy shared amongst partial epilepsy syndromes, in 3445 patients and 6935 controls of European ancestry. We did not identify any genome-wide significant association. A few single nucleotide polymorphisms may warrant further investigation. We exclude common genetic variants with effect sizes above a modest 1.3 odds ratio for a single variant as contributors to genetic susceptibility shared across the partial epilepsies. We show that, at best, common genetic variation can only have a modest role in predisposition to the partial epilepsies when considered across syndromes in Europeans. The genetic architecture of the partial epilepsies is likely to be very complex, reflecting genotypic and phenotypic heterogeneity. Larger meta-analyses are required to identify variants of smaller effect sizes (odds ratio<1.3) or syndrome-specific variants. Further, our results suggest research efforts should also be directed towards identifying the multiple rare variants likely to account for at least part of the heritability of the partial epilepsies. Data emerging from genome-wide association-studies will be valuable during the next serious challenge of interpreting all the genetic variation emerging from whole-genome sequencing studies.
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Epilepsias Parciales/diagnóstico , Epilepsias Parciales/genética , Predisposición Genética a la Enfermedad/genética , Variación Genética/genética , Estudio de Asociación del Genoma Completo/métodos , Femenino , Humanos , Internacionalidad , Masculino , Polimorfismo de Nucleótido Simple/genética , SíndromeRESUMEN
OBJECTIVE: Benign epileptiform transients of sleep (BETS) have a unique voltage topography and a posteriorly propagating, inferiorly rotating diphasic EEG pattern. The source generators of BETS have not been definitively identified. We aimed to clarify the cerebral localization of BETS using MEG and electromagnetic source imaging (EMSI). METHODS: We analyzed BETS recorded with simultaneous MEG and EEG in four patients with epilepsy. Magnetic source imaging (MSI) and EMSI using equivalent current, single moving and rotating dipole inverse models was performed on averaged BETS potentials. MEG beamforming was performed in one case with abundant BETS. RESULTS: MSI and EMSI revealed hippocampal dipole source maxima in all cases, with current flow direction rotating from inferomedial to superomedial or superolateral between the first and second BETS peaks. Moving dipole analyses revealed spatiotemporal propagation along the anterior-posterior hippocampal axis and concomitant electromagnetic field rotation. Beamformer source reconstruction revealed an identical hippocampal localization. CONCLUSIONS: Converging evidence from different electromagnetic inverse modeling methods indicates that BETS are traveling, rotating hippocampal spikes, whose diphasic waveform is due to back and forth propagation along the anterior-posterior axis of the hippocampus. SIGNIFICANCE: The hippocampal localization and longitudinal, rotating propagation pattern of BETS raises the possibility of a sleep-related functional role for these hippocampal spikes.
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Potenciales de Acción/fisiología , Electroencefalografía/métodos , Epilepsia/fisiopatología , Hipocampo/fisiología , Magnetoencefalografía/métodos , Sueño/fisiología , Adulto , Epilepsia/diagnóstico por imagen , Femenino , Hipocampo/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana EdadRESUMEN
Bilateral hypothalamic deep brain stimulation was performed to treat a patient with morbid obesity. We observed, quite unexpectedly, that stimulation evoked detailed autobiographical memories. Associative memory tasks conducted in a double-blinded "on" versus "off" manner demonstrated that stimulation increased recollection but not familiarity-based recognition, indicating a functional engagement of the hippocampus. Electroencephalographic source localization showed that hypothalamic deep brain stimulation drove activity in mesial temporal lobe structures. This shows that hypothalamic stimulation in this patient modulates limbic activity and improves certain memory functions.
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Estimulación Encefálica Profunda/métodos , Fórnix/fisiología , Hipotálamo/fisiología , Trastornos de la Memoria/terapia , Memoria/fisiología , Obesidad Mórbida/terapia , Apetito/fisiología , Regulación del Apetito/fisiología , Desnervación/métodos , Fórnix/anatomía & histología , Hipocampo/anatomía & histología , Hipocampo/fisiología , Humanos , Hipotálamo/anatomía & histología , Masculino , Persona de Mediana Edad , Vías Nerviosas/anatomía & histología , Vías Nerviosas/fisiología , Giro Parahipocampal/anatomía & histología , Giro Parahipocampal/fisiología , Resultado del TratamientoRESUMEN
Described here is a case of a patient who made the sign of the cross during right mesial temporal seizures, documented by intracranial depth electrode and simultaneous scalp video-EEG. The patient was ultimately found to have predominantly left temporal lobe epilepsy, and she was rendered seizure free for many years following a left anterior temporal lobe resection. Most interestingly, however, was a suggestion that in her case, making the sign of the cross may have represented a learned ictal behavioral phenomenon: the patient had been forced, over a period of many years, to make this gesture as an atonement in the postictal period. The movement ultimately came to be performed unconsciously, during the ictus, associated with a lateralized seizure discharge in the right temporal lobe. In contrast to seizure-induced experiential phenomena and typical motor automatisms, where the behavioral manifestations have no recognized association with learning, we wondered whether the pathophysiological mechanisms of chronic focal epilepsy had subserved in this case a psychological learning process, whereby right temporal seizures were ultimately able to recruit and activate an adjacent neural memory circuit.
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Automatismo/etiología , Epilepsias Parciales/complicaciones , Electroencefalografía/métodos , Epilepsias Parciales/cirugía , Femenino , Humanos , Persona de Mediana Edad , Pruebas NeuropsicológicasRESUMEN
It has long been recognized that insults to the cerebral cortex, such as trauma, ischaemia or infections, may result in the development of epilepsy, one of the most common neurological disorders. Human and animal studies have suggested that perturbations in neurovascular integrity and breakdown of the blood-brain barrier (BBB) lead to neuronal hypersynchronization and epileptiform activity, but the mechanisms underlying these processes are not known. In this study, we reveal a novel mechanism for epileptogenesis in the injured brain. We used focal neocortical, long-lasting BBB disruption or direct exposure to serum albumin in rats (51 and 13 animals, respectively, and 26 controls) as well as albumin exposure in brain slices in vitro. Most treated slices (72%, n = 189) displayed hypersynchronous propagating epileptiform field potentials when examined 5-49 days after treatment, but only 14% (n = 71) of control slices showed similar responses. We demonstrate that direct brain exposure to serum albumin is associated with albumin uptake into astrocytes, which is mediated by transforming growth factor beta receptors (TGF-betaRs). This uptake is followed by down regulation of inward-rectifying potassium (Kir 4.1) channels in astrocytes, resulting in reduced buffering of extracellular potassium. This, in turn, leads to activity-dependent increased accumulation of extracellular potassium, resulting in facilitated N-methyl-d-aspartate-receptor-mediated neuronal hyperexcitability and eventually epileptiform activity. Blocking TGF-betaR in vivo reduces the likelihood of epileptogenesis in albumin-exposed brains to 29.3% (n = 41 slices, P < 0.05). We propose that the above-described cascade of events following common brain insults leads to brain dysfunction and eventually epilepsy and suggest TGF-betaRs as a possible therapeutic target.
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Astrocitos/metabolismo , Epilepsia/fisiopatología , Neocórtex/fisiopatología , Receptores de Factores de Crecimiento Transformadores beta/fisiología , Albúmina Sérica/farmacocinética , Animales , Barrera Hematoencefálica/fisiopatología , Modelos Animales de Enfermedad , Regulación hacia Abajo , Electroencefalografía , Epilepsia/inducido químicamente , Epilepsia/metabolismo , Imagen por Resonancia Magnética , Neocórtex/efectos de los fármacos , Neocórtex/metabolismo , Neuronas/fisiología , Potasio/metabolismo , Canales de Potasio de Rectificación Interna/metabolismo , Ratas , Ratas Wistar , Albúmina Sérica/toxicidad , Técnicas de Cultivo de TejidosRESUMEN
Organophosphate pesticides (OPs), known inhibitors of acetylcholinesterase (AChE), are used extensively throughout the world. Recent studies have focused on the ACHE/PON1 locus as a determinant of inherited susceptibility to environmental OP exposure. To explore the relationship of the corresponding gene-environment interactions with brain activity, we integrated neurophysiologic, neuropsychological, biochemical, and genetic methods. Importantly, we found that subthreshold OP exposure leads to discernible physiological consequences that are significantly influenced by inherited factors. Cortical EEG analyses by LORETA revealed significantly decreased theta activity in the hippocampus, parahippocampal regions, and the cingulate cortex, as well as increased beta activity in the prefrontal cortex of exposed individuals-areas known to play a role in cholinergic-associated cognitive functions. Through neuropsychological testing, we identified an appreciable deficit in the visual recall in exposed individuals. Other neuropsychological tests revealed no significant differences between exposed and non-exposed individuals, attesting to the specificity of our findings. Biochemical analyses of blood samples revealed increases in paraoxonase and arylesterase activities and reduced serum acetylcholinesterase activity in chronically exposed individuals. Notably, specific paraoxonase genotypes were found to be associated with these exposure-related changes in blood enzyme activities and abnormal EEG patterns. Thus, gene-environment interactions involving the ACHE/PON1 locus may be causally involved in determining the physiological response to OP exposure.
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Arildialquilfosfatasa/genética , Inhibidores de la Colinesterasa/efectos adversos , Exposición a Riesgos Ambientales/efectos adversos , Neuronas/efectos de los fármacos , Plaguicidas/efectos adversos , Polimorfismo Genético , Acetilcolinesterasa/sangre , Arildialquilfosfatasa/sangre , Encéfalo/patología , Encéfalo/fisiopatología , Química Encefálica , Hidrolasas de Éster Carboxílico/sangre , Trastornos del Conocimiento/inducido químicamente , Trastornos del Conocimiento/genética , Electroencefalografía , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Recuerdo Mental , Neuronas/fisiología , Organofosfatos/efectos adversosRESUMEN
OBJECTIVE: To investigate the neurophysiological characteristics and prognostic impact of EEG synchronization with low frequency thalamic stimulation in patients with intractable epilepsy. METHODS: Electrical stimuli were delivered through deep brain stimulating (DBS) electrodes at 2, 5 or 10Hz to the anterior nucleus (AN) and the dorsomedial nucleus (DM) of six patients using the implanted programmable stimulation device. EEGs were recorded from 27 scalp electrodes. "Modeled" responses for 5 and 10Hz stimulation were computed based on the cerebral responses (CRs) evoked by "single pulse" (2Hz) stimulation and compared with the recorded EEG results. RESULTS: Rhythmic cortical 5Hz EEG synchronization occurred in 4/6 patients, with stimulation at 6/11 AN and 5/11 DM sites. Three of four patients with synchronization, but neither of the two patients without, had a significant reduction in seizure frequency. The magnitude of 5 and 10Hz EEG synchronization was positively related to the amplitudes of "single pulse" CRs. Simple temporal superposition of "single pulse" CRs resulted in "modeled" responses with strikingly similar morphology and scalp voltage distribution. CONCLUSIONS: Rhythmic EEG synchronization with low frequency stimulation primarily reflects spatiotemporal summation (interference) of "single pulse" CRs. SIGNIFICANCE: Rhythmic EEG synchronization might not serve as a physiologic verification of optimal localization of DBS electrodes. Its usefulness for the prediction of clinical efficacy is questionable.
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Sincronización Cortical , Estimulación Encefálica Profunda , Epilepsia/fisiopatología , Tálamo/fisiología , Adulto , Electrodos Implantados , Electroencefalografía , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: We investigated the relation between anterior thalamic stimulation and the morphology of the evoked cerebral responses (CRs) using intracerebral depth electrodes in patients with intractable epilepsy undergoing deep brain stimulation (DBS) of the thalamus. METHODS: Monopolar cathodic and bipolar stimuli were delivered at a rate of 2 or 1 Hz to the anterior nucleus (AN) and the dorsomedian nucleus (DM) of two patients using the programmable stimulation device (Medtronic ITREL II) or a GRASS stimulation device (S12). CRs were recorded from depth or DBS electrodes, situated bilaterally in mesial temporal (hippocampus, both patients), lateral temporal (one patient), orbitofrontal (Brodmann area 11, one patient) and anterior thalamic sites (one patient). RESULTS: The distribution and morphology of the CRs depended primarily on the site of stimulation within the anterior thalamic region. Overall, monopolar cathodic and bipolar stimulation of the AN elicited CRs mainly in ipsilateral mesial temporal cortical areas, whereas stimulation of the DM evoked high-amplitude CRs predominantly in ipsilateral orbitofrontal areas. The amplitude of the CR was positively related to the strength of the stimulus and generally higher with monopolar than with bipolar stimulation. The differences between CRs elicited during wakefulness or slow wave sleep were minimal. CONCLUSIONS: The distribution of the CRs corresponded with the intracerebral pathways of the involved structures and the findings are in good accordance with those of our previous study investigating the sources of CRs using statistical non-parametric mapping of low resolution electromagnetic tomography (LORETA) values. SIGNIFICANCE: Our findings indicate a certain degree of point-to-point specificity within the thalamocortical circuitry, which may make optimal localization of DBS electrodes important in patients with epilepsy.
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Núcleos Talámicos Anteriores/efectos de la radiación , Corteza Cerebral/fisiopatología , Estimulación Encefálica Profunda/métodos , Epilepsia/terapia , Adulto , Núcleos Talámicos Anteriores/fisiopatología , Mapeo Encefálico , Electrodos , Electroencefalografía , Epilepsia/patología , Femenino , Lateralidad Funcional/efectos de la radiación , Humanos , Imagen por Resonancia Magnética/métodos , MasculinoRESUMEN
OBJECTIVE: We have investigated the cortical sources and electroencephalographic (EEG) characteristics of small sharp spikes (SSS) by using statistical non-parametric mapping (SNPM) of low resolution electromagnetic tomography (LORETA). METHODS: We analyzed 7 SSS patterns (501 individual SSS) in 6 patients who underwent sleep EEG studies with 29 or 23 scalp electrodes. The scalp signals were averaged time-locked to the SSS peak activity and subjected to SNPM of LORETA values. RESULTS: All 7 SSS patterns (mean 72 individual SSS, range 11-200) revealed a very similar and highly characteristic transhemispheric oblique scalp voltage distribution comprising a first negative field maximum over ipsilateral lateral temporal areas, followed by a second negative field maximum over the contralateral subtemporal region approximately 30 ms later. SNPM-LORETA consistently localized the first component into the ipsilateral posterior insular region, and the second component into ipsilateral posterior mesial temporo-occipital structures. CONCLUSIONS: SSS comprise an amalgam of two sequential, distinct cortical components, showing a very uniform and peculiar EEG pattern and cortical source solutions. As such, they must be clearly distinguished from interictal epileptiform discharges in patients with epilepsy. SIGNIFICANCE: The awareness of these peculiar EEG characteristics may increase our ability to differentiate SSS from interictal epileptiform activity. The finding of a posterior insular source might serve as an inspiration for new physiological considerations regarding these enigmatic waveforms.
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Mapeo Encefálico/métodos , Electroencefalografía/métodos , Epilepsia del Lóbulo Temporal/diagnóstico , Epilepsia del Lóbulo Temporal/fisiopatología , Lóbulo Temporal/fisiología , Adulto , Femenino , Lateralidad Funcional , Humanos , Masculino , Persona de Mediana Edad , Cuero Cabelludo , Sueño/fisiologíaRESUMEN
Electroecenphalography (EEG) is an integral part of the diagnostic process in patients with Creutzfeldt-Jakob disease (CJD). The EEG has therefore been included in the World Health Organisation diagnostic classification criteria of CJD. In sporadic CJD (sCJD), the EEG exhibits characteristic changes depending on the stage of the disease, ranging from nonspecific findings such as diffuse slowing and frontal rhythmic delta activity (FIRDA) in early stages to disease-typical periodic sharp wave complexes (PSWC) in middle and late stages to areactive coma traces or even alpha coma in preterminal EEG recordings. PSWC, either lateralized (in earlier stages) or generalized, occur in about two-thirds of patients with sCJD, with a positive predictive value of 95%. PSWC occur in patients with methionine homozygosity and methionine/valine heterozygosity but only rarely in patients with valine homozygosity at codon 129 of the prion protein gene. PSWC tend to disappear during sleep and may be attenuated by sedative medication and external stimulation. Seizures are an uncommon finding, occurring in less than 15% of patients with sCJD. In patients with iatrogenic CJD, PSWC usually present with more regional EEG findings corresponding to the site of inoculation of the transmissible agent. In genetic CJD, PSWC in its typical form are uncommon, occurring in about 10%. No PSWC occur in EEG recordings of patients with variant CJD.
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Síndrome de Creutzfeldt-Jakob/diagnóstico , Síndrome de Creutzfeldt-Jakob/fisiopatología , Ritmo Delta , Electroencefalografía/métodos , Animales , Mapeo Encefálico , Síndrome de Creutzfeldt-Jakob/genética , Humanos , Valor Predictivo de las PruebasRESUMEN
OBJECTIVE: We have investigated intracerebral propagation of interictal epileptiform discharges (IED) in patients with mesial temporal lobe epilepsy (MTLE) by using spatiotemporal source maps based on statistical nonparametric mapping (SNPM) of low resolution electromagnetic tomography (LORETA) values. METHODS: We analyzed 30 patterns of IED recorded simultaneously with scalp and intracranial foramen ovale (FO) electrodes in 15 consecutive patients with intractable MTLE. The scalp EEG signals were averaged time-locked to the peak activity in bilateral 10-contact FO electrode recordings. SNPM was applied to LORETA values and spatiotemporal source maps were created by allocating the t-values over time to their corresponding Brodmann areas. Propagation was defined as secondary statistically significant involvement of distinct cortical areas separated by >15 ms. The results were correlated with intracranial data obtained from FO electrode recordings and with scalp EEG recordings. All patients underwent subsequent amygdalo-hippocampectomy and outcome was assessed one year after surgery. RESULTS: We found mesial to lateral propagation in 6/30 IED patterns (20%, four patients), lateral to mesial propagation in 4/30 IED patterns (13.3%, four patients) and simultaneous (within 15 ms) activation of mesial and lateral temporal areas in 6/30 IED patterns (20%, five patients). Propagation generally occurred within 30 ms and was always limited to ipsilateral cortical regions. Nine/30 IED patterns (30%) showed restricted activation of mesial temporal structures and no significant solutions were found in 5/30 IED patterns (16.7%). There was no clear association between the number or characteristics of IED patterns and the postsurgical outcome. CONCLUSIONS: Spatiotemporal mapping of SNPM LORETA accurately describes mesial to lateral temporal propagation of IED, and vice versa, which commonly occur in patients with MTLE. SIGNIFICANCE: Intracerebral propagation must be considered when using non-invasive source algorithms in patients with MTLE. Spatiotemporal mapping might be useful for visualizing this propagation.
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Mapeo Encefálico , Electroencefalografía , Epilepsia del Lóbulo Temporal/patología , Epilepsia del Lóbulo Temporal/fisiopatología , Hueso Esfenoides , Adulto , Algoritmos , Electrodos , Femenino , Lateralidad Funcional/fisiología , Humanos , Masculino , Persona de Mediana Edad , Estadística como AsuntoRESUMEN
OBJECTIVE: Subclinical rhythmic electrographic discharges of adults (SREDA) is currently considered a benign EEG pattern of uncertain significance. The underlying cortical sources and generating mechanisms are unknown. We performed a source localization analysis of SREDA with the aim of better understanding this unusual EEG pattern. METHODS: Multiple spontaneous episodes of typical SREDA were recorded in a patient during continuous EEG monitoring. Additional SREDA episodes were induced by hyperventilation. Source localization was carried out using statistical non-parametric mapping (SNPM) of low resolution electromagnetic tomography (LORETA). RESULTS: SNPM of both time- and frequency-domain LORETA revealed a widespread biparietal cortical origin of SREDA, the anatomical distribution of which included the parietal operculum and the known vascular watershed areas between anterior, middle and posterior cerebral arteries. Vigorous deep hyperventilation induced SREDA on three of four attempts. Mean duration of the hyperventilation-induced SREDA was approximately three times longer than spontaneous events. CONCLUSIONS: Investigations in this patient with typical SREDA revealed hyperventilation sensitivity and a posterior hemispheric source localization maximal in the parietal cortex bilaterally, in large part overlying the anatomical distribution of the vascular watershed areas. SIGNIFICANCE: The source localization results and sensitivity to hyperventilation suggest some sort of association between cerebral vascular supply and SREDA, as originally proposed by Naquet et al. [Naquet R, Louard C, Rhodes J, Vigouroux M. A propos de certaines décharges paroxystiques du carrefour temporo-pariéto-occipital. Leur activation par l'hypoxie. Rev Neurol 1961;105:203-207.].
Asunto(s)
Encefalopatías/fisiopatología , Electroencefalografía , Hiperventilación/fisiopatología , Lóbulo Parietal/fisiología , Anciano , Anticonvulsivantes/uso terapéutico , Encefalopatías/tratamiento farmacológico , Humanos , Imagen por Resonancia Magnética , Masculino , Ácido Valproico/uso terapéuticoRESUMEN
OBJECTIVE: To investigate the localization accuracy of low-resolution electromagnetic tomography (LORETA) for mesial temporal interictal epileptiform discharges (IED) using a new relative averaging (RELAVG) technique for noise reduction. METHODS: We analyzed 19 patterns of mesial temporal IED recorded simultaneously with scalp and foramen ovale (FO) electrodes in 15 consecutive patients who underwent presurgical assessment for intractable temporal lobe epilepsy. The scalp signals were time-locked to the peak activity in the FO electrode recordings and source modeling was performed using the RELAVG technique. Random noise of various amounts was then applied. The results were compared to intracranial data obtained from the FO electrode recordings and to LORETA source solutions obtained using two other approaches to improve signal to noise ratio (SNR): statistical non-parametric mapping (SNPM) and the commonly applied averaging (AVG) technique. RESULTS: The RELAVG technique allowed for reasonable mesial temporal localization in 52.6% (10/19) of IED patterns, compared with 73.7% (14/19) using SNPM. The AVG technique provided no strictly mesial temporal solutions. Nine of the IED patterns revealed relative current density quotient changes >10; all of these were accurately localized by RELAVG into mesial temporal structures. Increasing amounts of white and physiological noise had no influence on the accuracy of RELAVG and SNPM solutions, whereas AVG source reconstructions became progressively spurious. CONCLUSION: The RELAVG technique and SNPM, but not the commonly used AVG technique, allow for reasonable source localization of mesial temporal IED. SNPM is the most accurate but also the most time-consuming noise reduction technique. SIGNIFICANCE: The RELAVG LORETA technique might provide a simple and fast semi-quantitative alternative for localizing IED with low single to noise ratio.
Asunto(s)
Mapeo Encefálico , Electroencefalografía/estadística & datos numéricos , Epilepsia/fisiopatología , Adulto , Diagnóstico por Computador/métodos , Electrodos , Electroencefalografía/métodos , Femenino , Humanos , MasculinoRESUMEN
OBJECTIVE: We studied the relation between thalamic stimulation parameters and the morphology, topographic distribution and cortical sources of the cerebral responses in patients with intractable epilepsy undergoing deep brain stimulation (DBS) of the thalamus. METHODS: Bipolar and monopolar stimuli were delivered at a rate of 2 Hz to the anterior (AN, four patients), the dorsomedian (DM, four patients), and the centromedian nucleus (CM, one patient) using the programmable stimulation device (Medtronic ITREL II). Source modeling was carried out by using statistical non-parametric mapping of low-resolution electromagnetic tomography (LORETA) values. RESULTS: All patients demonstrated reproducible time-locked cortical responses (CRs) consisting of a sequence of components with latencies between 20 and 320 ms. The morphology of these CRs, however, was very heterogeneous, depending primarily on the site of stimulation. Following AN stimulation, cortical activation was most prominent in ipsilateral cingulate gyrus, insular cortex and lateral neocortical temporal structures. Stimulation of the DM mainly showed activation of the ipsilateral orbitofrontal and mesial and lateral frontal areas, but also involvement of mesial temporal structures. Stimulation of the CM showed a rather diffuse (though still mainly ipsilateral) increase of cortical activity. The magnitude of cortical activation was positively related to the strength of the stimulus and inversely related to the impedance of the electrode. CONCLUSIONS: The pattern of cortical activation corresponded with the hodology of the involved structures and may underscore the importance of optimal localization of DBS electrodes in patients with epilepsy. SIGNIFICANCE: The method of analyzing sources of CRs could potentially be a useful tool for titration of DBS parameters in patients with electrode contacts in clinically silent areas. Furthermore, the inverse relation of the cortical activation and the impedance of the electrode contacts might suggest that these impedance measurements should be taken into consideration when adjusting DBS parameters in patients with epilepsy.
Asunto(s)
Corteza Cerebral/fisiopatología , Estimulación Encefálica Profunda/métodos , Epilepsia/terapia , Tálamo/efectos de la radiación , Adulto , Mapeo Encefálico , Corteza Cerebral/efectos de la radiación , Relación Dosis-Respuesta en la Radiación , Impedancia Eléctrica/uso terapéutico , Electrodos , Electroencefalografía/métodos , Epilepsia/patología , Femenino , Lateralidad Funcional , Humanos , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
OBJECTIVE: Middle-latency somatosensory evoked potentials (SEPs) following median nerve stimulation can provide a sensitive measure of cortical function. We sought to determine whether the mechanical forces of whiplash injury or concussion alter normal processing of middle-latency SEPs. METHODS: In a cross-sectional pilot study 20 subjects with whiplash were investigated (50% between 0.5-2 months and 50% between 6-41 months post injury) and compared to 83 healthy subjects using a standard middle-latency SEP procedure. In a subsequent prospective study subjects with either acute whiplash (n=13) or Grade 3 concussion (n=16) were investigated within 48 hours and again three months post injury. RESULTS: In the pilot study the middle-latency SEP component N60 was significantly increased in the ten subjects investigated within two months after whiplash. In contrast, the ten subjects examined more than six months after injury showed normal latencies. In the prospective study N60 latencies were increased after whiplash and concussion when tested within 48 hours of injury. At three months, latencies were improved though still significantly different from controls post whiplash and concussion. CONCLUSIONS: Both whiplash injury and concussion alter processing of the middle-latency SEP component N60 in the acute post traumatic period. The acute changes appear to normalize between three-six months post injury. The SEP similarities suggest that the overlapping clinical symptomatology post whiplash and concussion may reflect a similar underlying mechanism of rotational mild traumatic brain injury.