The effects of focal epileptic activity on regional sensory-evoked neurovascular coupling and postictal modulation of bilateral sensory processing.

While it is known that cortical sensory dysfunction may occur in focal neocortical epilepsy, it is unknown whether sensory-evoked neurovascular coupling is also disrupted during epileptiform activity. Addressing this open question may help to elucidate both the effects of focal neocortical epilepsy on sensory responses and the neurovascular characteristics of epileptogenic regions in sensory cortex. We therefore examined bilateral sensory-evoked neurovascular responses before, during, and after 4-aminopyridine (4-AP, 15 mmol/L, 1 µL) induced focal neocortical seizures in right vibrissal cortex of the rat. Stimulation consisted of electrical pulse trains (16 seconds, 5 Hz, 1.2 mA) presented to the mystacial pad. Consequent current-source density neural responses and epileptic activity in both cortices and across laminae were recorded via two 16-channel microelectrodes bilaterally implanted in vibrissal cortices. Concurrent two-dimensional optical imaging spectroscopy was used to produce spatiotemporal maps of total, oxy-, and deoxy-hemoglobin concentration. Compared with control, sensory-evoked neurovascular coupling was altered during ictal activity, but conserved postictally in both ipsilateral and contralateral vibrissal cortices, despite neurovascular responses being significantly reduced in the former, and enhanced in the latter. Our results provide insights into sensory-evoked neurovascular dynamics and coupling in epilepsy, and may have implications for the localization of epileptogenic foci and neighboring eloquent cortex.

Comparison of heart rate variability parameters during complex partial seizures and psychogenic nonepileptic seizures.

PURPOSE: Psychogenic nonepileptic seizures (PNES) superficially resemble epileptic seizures. Little is known about ictal autonomic nervous system (ANS) activity changes in epilepsy and PNES. This study compares ictal heart rate variability (HRV) parameters as a reflection of ANS tone in epileptic seizures and PNES, and explores differences between interictal and ictal ANS tone in both patient groups. METHODS: Ictal HRV parameters were extracted from single-lead electrocardiography (ECG) data collected during video-electroencephalography (EEG) recordings of 26 patients with medically refractory temporal lobe epilepsy and 24 age- and sex-matched patients with PNES. One seizure per patient in a resting, wake, supine state was analyzed. Interictal ECG data were available for comparison from 14 patients in both groups. HRV parameters in time and frequency domains were analyzed (low frequency [LF], high frequency [HF], standard deviation of all consecutive normal R wave intervals [SDNN], square root of the mean of the sum of the squares of differences between adjacent normal R wave intervals [RMSSD]). CVI (cardiovagal index), CSI (cardiosympathetic index), and ApEn (approximate entropy) were calculated from Lorenz plots. KEY FINDINGS: There were significant differences between ictal HRV measures during epileptic and nonepileptic seizures in the time and frequency domains. CSI (p < 0.001) was higher in epileptic seizures. Time interval between two consecutive R waves in the ECG (RR interval) (p = 0.002), LF (p = 0.02), HF (p = 0.003), and RMSSD (p = 0.003) were significantly lower during epileptic seizures. Binary logistic regression yielded a significant model based on the differences in CSI classifying 88% of patients with epilepsy and 73% of patients with PNES correctly. The comparison between resting and ictal states in both seizure disorders revealed significant differences in RR interval (epilepsy p < 0.001, PNES p = 0.01), CSI (epilepsy p < 0.001, PNES p = 0.02), HF (epilepsy p = 0.002, PNES p = 0.03), and RMSSD (epilepsy p = 0.004, PNES p = 0.04). In patients with epilepsy there were also significant differences in ictal versus interictal mean values of ApEn (p = 0.03) and LF (p = 0.04). Although CSI was significantly higher, the other parameters were lower during the seizures. Stepwise binary regression in the 14 patients with epilepsy produced a significant model differentiating resting state from seizures in 100% of cases. The same statistical approach did not yield a significant model in the PNES group. SIGNIFICANCE: Our results show greater ANS activation in epileptic seizures than in PNES. The biggest ictal HRV changes associated with epileptic seizures (CSI, HF, and RMSSD) reflect high sympathetic system activation and reduced vagal tone. The reduced ApEn also reflects a high sympathetic tone. The observed ictal alterations of HRV patterns may be a more specific marker of epileptic seizures than heart rate changes alone. These altered HRV patterns could be used to detect seizures and also to differentiate epileptic seizures from PNES. Larger studies are justified with intergroup and intragroup comparisons between ictal and resting states.

Persistent ictal-like visual cortical excitability in chronic migraine.

Episodic migraine (EM) may evolve into the more disabling chronic migraine (CM, monthly migraine days ≥ 8 and headache days ≥ 15) with unknown mechanism. Aiming to elucidate the pathophysiology of CM and its relationship with EM, this study characterized the visual cortical responses in CM and EM. Neuromagnetic visual-evoked responses to left-hemifield checkerboard reversals were obtained in patients with EM (interictal or ictal states), CM (interictal) and age-matched controls. For each subject, the 1500 evoked responses were sequentially divided into 30 blocks and percentage changes of P100m amplitude in blocks 2, 9, 16, 23, and 30 compared to the first block were computed to assess habituation. At the end of visual stimulation (block 30), P100m amplitude was decreased (habituated) in the controls (n=32) (35.2±2.6nAm vs. 41.9±2.7, p=0.005) but increased (potentiated) in the interictal state of EM (n=29) (39.7±3.8 vs. 33.5±3.0, p=0.007). In CM (n=25), P100m was habituated (46.5±2.9 vs. 51.6±3.7, p=0.013) but higher at the initial block than in those of the interictal state of EM (p=0.001). These CM features also characterized the P100m in the ictal state of EM (n=9). There was no difference of P100m between CM and ictal state of EM. In conclusion, patients with CM demonstrate a persistent ictal-like excitability pattern of the visual cortex between migraine attacks which may implicate central inhibitory dysfunction.

Modelos experimentales en epilepsia / Experimental models in epilepsy

Introducción: La epilepsia es una de las enfermedades neurológicas más frecuentes, y además conlleva una tasa de consecuencias negativas muy importante, tanto para el paciente como para los familiares. Su manifestación clínica principal es la aparición de crisis epilépticas recurrentes, que en el 70-80% de los casos se controlan con la medicación. Sin embargo, a pesar de que van apareciendo nuevos fármacos para el control de las crisis, no disponemos todavía de fármacos que consigan evitar la epileptogénesis. Método: Revisamos las publicaciones más relevantes de modelos animales experimentales en epilepsia utilizando para ello la base de datos de PubMed. Resultados: Se han encontrado un amplio número de publicaciones sobre tipos de modelos experimentales tanto genéticos (transgénicos, genéticamente determinados) como lesionales (químicos o eléctricos), que intentan imitar los diferentes tipos de epilepsia en humanos. Conclusiones: A pesar de que en las últimas décadas se han hecho importantes avances en el campo de la epilepsia, aún quedan muchos aspectos por dilucidar. En este sentido, los modelos experimentales pueden suponer una herramienta muy útil para el avance en el conocimiento de los mecanismos fisiopatológicos y en la búsqueda de tratamientos eficaces (AU)

Introduction: Epilepsy is one of the neurological pathologies with the highest rate of incidence and with a significant number of negatives consequences. Current pharmacological treatments have an antiepileptic effect, allowing control over 70% of the patients, but they are not able to prevent the development of epileptogenesis from occurring. Method: Ee have reviewed the most relevant publications of experimental animal models with epilepsy by using the PubMed data base. Results: We found a large number of publications related to different kinds of experimental models, both genetic (transgenic, genetically determined) and lesional which appeared to resemble the different types of human epilepsy. Conclusions: Even though many important improvements have been accomplished in the area of epilepsy in the last decades, there are still many aspects to be clarified. In this regard, experimental models might become a very useful means for a better understanding of pathophysiological mechanisms and in the search for more efficient treatments (AU)

Disruption of LGI1-linked synaptic complex causes abnormal synaptic transmission and epilepsy.

Epilepsy is a devastating and poorly understood disease. Mutations in a secreted neuronal protein, leucine-rich glioma inactivated 1 (LGI1), were reported in patients with an inherited form of human epilepsy, autosomal dominant partial epilepsy with auditory features (ADPEAF). Here, we report an essential role of LGI1 as an antiepileptogenic ligand. We find that loss of LGI1 in mice (LGI1(-/-)) causes lethal epilepsy, which is specifically rescued by the neuronal expression of LGI1 transgene, but not LGI3. Moreover, heterozygous mice for the LGI1 mutation (LGI1(+/-)) show lowered seizure thresholds. Extracellularly secreted LGI1 links two epilepsy-related receptors, ADAM22 and ADAM23, in the brain and organizes a transsynaptic protein complex that includes presynaptic potassium channels and postsynaptic AMPA receptor scaffolds. A lack of LGI1 disrupts this synaptic protein connection and selectively reduces AMPA receptor-mediated synaptic transmission in the hippocampus. Thus, LGI1 may serve as a major determinant of brain excitation, and the LGI1 gene-targeted mouse provides a good model for human epilepsy.

Computational modeling of high-frequency oscillations at the onset of neocortical partial seizures: from 'altered structure' to 'dysfunction'.

In this paper, a neural mass model is proposed to analyze some mechanisms underlying the generation of fast oscillations (80 Hz and beyond) at the onset of seizures. This model includes one sub-population of pyramidal cells and one sub-population of interneurons targeting the perisomatic region of pyramidal cells where fast GABAergic currents are mediated. We identified some conditions for which the model can reproduce the features of high-frequency, chirp-like (from approximately 100 to approximately 70 Hz) signatures observed in real depth-EEG signals recorded in epileptic patients at seizure onset ("fast onset activity"). These conditions included appropriate alterations in (i) the strengths of GABAergic and glutamatergic connections, and (ii) the amplitude of average EPSPs/IPSPs. Results revealed that a subtle balance between excitatory and inhibitory feedbacks is required in the model for reproducing a 'realistic' fast activity, i.e., showing a reduction of frequency with a simultaneous increase in amplitude, as actually observed in epileptogenic cerebral cortex. Results also demonstrated that the number of scenarios (variation, in time, of model parameters) leading to chirp-like signatures was rather limited. First, to produce high-frequency output signals, the model should operate in a "resonance" region, at the frontier between a stable and an unstable region. Second both EPSP and IPSP amplitudes should decrease with time in order to obey the frequency/amplitude constraint. These scenarios obtained through a mathematical analysis of the model show how some alteration in the structure of neural networks can lead to dysfunction. They also provide insights into potentially important mechanisms for high-frequency epileptic activity generation.

Long-term outcome of lesional posterior cortical epilepsy surgery in adults.

OBJECTIVE: The aim of this study was to evaluate the short- and long-term seizure outcome and to find predictors of outcome after epilepsy surgery in lesional posterior cortical epilepsies (PCEs). METHODS: The operative outcome in 80 consecutive adult patients with lesional PCEs who underwent resective surgery for intractable partial epilepsy between 1991 and 2006 was retrospectively studied. RESULTS: The probability of remaining in Engel Class I was 66.3% (95% CI 60 to 72) at 6 months, 52.5% (95% CI 47 to 57) at 2 years, 52.9% (CI 45 to 59) at 5 years and 47.1% (CI 42 to 52) at 10 years. Factors predicting poor outcome were the presence of a somatosensory aura, extraregional spikes, incomplete resection, interictal epileptiform discharge (IED) in EEG 6 months and 2 years postsurgery, history of generalised tonic-clonic seizure (GT-CS) and the presence of focal cortical dysplasia in the resected specimen. Factors predicting good outcome were childhood onset of epilepsy, short epilepsy duration, ipsilateral spikes, visual aura, presence of well-circumscribed lesion in preoperative MRI and a pathologically defined tumour. In the multivariate analysis, predictors were different in the long and short term as follows: incomplete resection as proven by postoperative MRI (hazard ratio (HR) 2.059 (CI 1.19 to 3.67)) predicts seizure relapse in short-term follow-up. The presence of IED in the EEG performed 6 months after surgery (HR 2.3 (CI 1.128 to 4.734)) predicts seizure relapse in the long-term fellow-up. However, the absence of a history of GT-CS independently predicts seizure remission in short- and long-term follow-up. CONCLUSIONS: Surgery in PCEs proved to be effective in short- and long-term follow-up. Lesional posterior cortical epilepsy may be a progressive process in a substantial number of cases.

Diagnostic value and safety of long-term video-EEG monitoring.

This paper aimed to assess the usefulness and safety of video-EEG (video-electroencephalography) monitoring in patients with refractory epilepsy. We analysed the video-EEG recordings of consecutive patients over a 3-year period from 2002 to 2005. The pre-admission diagnosis, demographic information, number of ictal episodes, adverse events, and final diagnosis were recorded in all patients. The diagnostic labels before and after monitoring were compared in order to assess whether it had led to a change in diagnosis and management. Of the 100 patients who underwent video-EEG, 227 clinical events were recorded in 62 cases. The most common events were complex partial seizures followed by non-epileptic attacks. Video-EEG allowed a diagnosis to be made in 81 patients and the diagnosis at discharge was altered in 19 cases. Major injuries and status epilepticus did not occur during monitoring. In our experience video-EEG is safe and provides important clinical information in over 80% of patients.

Influence of levetiracetame on ictal and postictal EEG in patients with partial seizures.

To investigate the influence of levetiracetame (LEV) treatment on the interhemispheric seizure pattern propagation and postictal recovery of electroencephalography (EEG) background activity. Twenty-three adult patients (age > 16 years) with pharmacoresistant focal epilepsies presenting at the Epilepsy Center Erlangen for pre-surgical evaluation were enrolled in the study. Those eligible patients receiving only one antiepileptic drugs were recruited to the 48-h baseline phase and, after at least two seizures, were randomized to the 7-day treatment phase with either LEV (n = 11) or placebo (n = 12). All participants were submitted to continuous day-and-night video-EEG monitoring. The daily dose of LEV was 1000 mg (500 mg bid.) on the first treatment day and was increased to 2000 mg (1000 mg bid.) from the second day onward. The EEG changes relating to the time delay of the interhemispheric seizure pattern propagation and to the postictal recovery of the background activity were analysed by computerized video-EEG recording and compared using the non-parameter Mann-Whitney U-exact test (alpha = 0.05). A prolonged latency of the contralateral seizure pattern propagation was observed in the LEV group, whereas a more rapid propagation was observed in the placebo group (P = 0.009). Postictal generalized slowing of the background activity was recorded in 21 patients during the baseline phase. More rapid postictal recovery of the EEG background activity was observed in the LEV, but not in the placebo group (P = 0.03). This study demonstrated that LEV not only prevented the seizure pattern propagation but also helped the speedy recovery of the postictal background activity in the EEG.

[Reverse crossed cerebellar diaschisis]. / Diaschisis cerebelosa cruzada reversa.

Cerebral Magnetic Resonance imaging in acute postictal period is performed to exclude structural processes that can be responsible for the epileptic activity. Sometimes, the findings are the result of the epileptic activity, and not the cause reflecting the pathophysiologic changes during epileptic activity. In this paper we describe a patient with status epilepticus who has developed hemicerebellar involvement contralateral to a frontal epileptogenic focus. This phenomenon of Reverse Crossed Cerebellar Diaschisis is rare and has been describe only in Single Photon Emission Computed Tomography (SPECT).

[Supplementary sensory-motor seizures--symptomatology, etiology, and surgical management with illustrative case reports]. / A szupplementer szenzomotoros rohamok tünettana, kóreredete és mutéti kezelhetosége, illusztratív esetismertetésekkel.

In the past decade, owing to the advance of epilepsy surgery, growing knowledge has accumulated on the role of the supplementary motor area, described by Penfield and coworkers in the early fifties, in movement regulation and on the characteristics of seizures involving this area. In the Hungarian neurological literature this topic--despite its neurophysiological and practical clinical importance--has been hardly touched. The authors, based on their own experience obtained from surgeries performed within the framework of the "Co-operative Epilepsy Surgery Program", describe the electrophysiological features of this area, its role in movement regulation and the symptoms of epileptic seizures stemmed from or spread onto this area. Using cases as illustrations, they demonstrate the reasoning and various algorithms of the multidisciplinary examination necessary to explore the seizure onset zone and the pathways of seizure spread. Details of the surgical solution are also described.

Simple partial seizures with hemisensory phenomena and dysgeusia: an insular pattern.

Insular seizures are rarely described, in part owing to the complex anatomy of this brain region. We present a patient with simple partial seizures, recorded intracranially, originating in the right insula and characterized by dysgeusia and contralateral somatosensory phenomena. This rare clinical pattern seems to be characteristic of the insula and may be undetectable with surface EEG.

Symptoms in focal sensory seizures. Clinical and electroencephalographic features.

PURPOSE: Aura is a brief subjective symptom that may represent the initial manifestation of a partial epileptic seizure with objective signs or constitute the entire epileptic attack (focal sensory seizure (FSS)). We studied the electro-clinical features of FSSs recorded in 28 patients. METHODS: Using long-term surface video-EEG recordings, we examined 28 patients (from a consecutive series of 64) with stereotyped FSSs and complex partial seizures (CPS) preceded in at least one instance by identical subjective manifestations (overall 255 FSSs and 39 CPS were recorded). FSSs were subdivided according to the type of sensation into somatosensory, visual or oculosensory, viscerosensory, experiential, cephalic and diffuse warm sensations. The EEG discharges accompanying FSSs were examined by two of the authors either blinded as to the type and timing of the seizure, or unblinded, i.e. after receiving complete clinical information including timing of the patient's warning. RESULTS: The ictal pattern accompanying FSSs was identified blind in 13 patients and unblind in 8 patients. In seven patients, the ictal discharge remained undetected. In the cases with recognizable ictal abnormalities, two main patterns could be distinguished, static and dynamic. FSSs whose ictal discharge could be recognized by blind EEG examination more frequently consisted of somatosensory and visual or oculosensory manifestations, and the discharge generally involved the centro-parieto-occipital regions. The ictal discharge of viscerosensory and experiential FSSs more easily remained undetected; when identified, it generally involved the fronto-temporal regions. CONCLUSIONS: FSSs are often accompanied by ictal abnormalities recognizable on surface EEG. A thorough knowledge of their EEG accompaniments may be a useful diagnostic aid in patients with partial epilepsy.

LGI1 gene mutation screening in sporadic partial epilepsy with auditory features.

Partial epilepsy with auditory features occasionally segregates in families as an autosomal dominant trait. In some families mutations in the leucine-rich glioma inactivated (LGI1) gene have been identified. Sporadic cases might harbour either denovo or low-penetrant LGI1 mutations, which will substantially alter the family risk for epilepsy. We selected sixteen sporadic patients with cryptogenic temporal lobe epilepsy and partial seizures with auditory features. We compared clinical features of these patients with those of published autosomal dominant family cases. We screened these patients for LGI1 mutations. Comparing the sporadic patients with the published familial cases no difference in either the primary auditory features or in the other associated epileptic manifestations was identified. Sequence analysis of the whole LGI1 gene coding regions in sporadic patients did not reveal changes in the LGI1 gene. The genetic analysis demonstrates that LGI1 is not a major gene for sporadic cases of partial epilepsy with auditory features at least in the Italian population. Screening of sporadic patients for LGI1 mutations appears not useful in genetic counselling of these patients.

The predictive localizing value of tonic limb posturing in supplementary sensorimotor seizures.

OBJECTIVE: To determine whether early tonic limb posturing is reliable in lateralizing or localizing of the seizure generator in 14 patients with pharmacoresistent supplementary sensorimotor area (SSMA) seizures. METHODS: All patients underwent high-quality MRI scans and stereo-EEG recordings. RESULTS: The SSMA seizure semiology predicted focal or regional ictal onset in the SSMA in six (43%) patients: Three had a focal SSMA seizure onset, and three had a regional seizure onset with involvement of one SSMA plus adjacent neocortex. The eight remaining patients had diffuse uni- or bilateral seizure onset. Eight of 14 patients underwent a frontal or central cortical resection, but a good outcome was seen in only 3: 2 with no SSMA resection and 1 with an extensive central removal. CONCLUSIONS: SSMA semiology is suggestive of early involvement of this region but is by no means a reliable indicator that the primary SSMA contains the seizure focus.

The significance of ear plugging in localization-related epilepsy.

PURPOSE: The localizing value of ear plugging in the treatment of auditory onset partial seizures, to our knowledge, has not been previously described. We propose that ear plugging is a clinical response to a sensory seizure manifested as an auditory hallucination and a tool for identifying the seizure focus in the auditory cortex on the superior temporal gyrus. METHODS: We report on three children who had prior epilepsy surgery for recurrent symptomatic localization-related epilepsy and who, subsequent to their surgery, displayed stereotyped unilateral or bilateral ear plugging at the onset of partial seizures. We studied scalp video electroencephalography (VEEG), magnetoencephalography (MEG), and magnetic resonance imaging (MRI) in all three. Additionally, we used electrocorticography (ECoG) in two patients, intracranial VEEG monitoring in one patient, and functional MRI language mapping in two patients. RESULTS: All three patients plugged their ears with their hands during auditory auras that localized to the superior temporal gyrus and were followed by partial seizures that spread to a wider field, as shown on scalp and intracranial VEEG. All three patients had MEG interictal discharges in the superior temporal gyrus. One patient who was nonverbal and unable to describe an auditory phenomenon plugged the ear contralateral to where temporal lobe-onset seizures and MEG interictal discharges occurred. CONCLUSIONS; Ear-plugging seizures indicate an auditory aura and may also lateralize seizure onset to the contralateral temporal lobe auditory cortex. Stereotyped behaviors accompanied by epileptic seizures in children who have poor communication skills are important in the seizure semiology of localization-related epilepsy.

Epileptic kinetopsia: ictal illusory motion perception.

A 38-year-old woman with a right posterior temporo-occipital brain tumor developed partial seizures with illusory motion perception of environmental objects going from the center to the periphery within her left visual field. Subdural EEG recordings during visual seizures revealed onsets in the right temporo-parieto-occipital junction. Her ictal visual distortion was probably caused by activation of V5, an area involved in motion perception. Given that the tumor location corresponds with the ictal onset in the V5 area, and the semiology of her seizures, this case supports that epileptic dysfunction in V5 can cause illusions of visual motion.