Ictal EEG-fMRI in localization of epileptogenic area in patients with refractory neocortical focal epilepsy.

PURPOSE: To evaluate the usefulness of ictal electroencephalography (EEG)-combined functional magnetic resonance imaging ( MRI) (EEG-fMRI) in localizing epileptogenic zone in refractory neocortical focal epilepsy. METHODS: From the EEG-fMRI database of our institution including 62 adult patients, 14 (age 18-46 years) experienced some ictal event during the test. Data were segmented into 10-s blocks, and the results were analyzed by contrasting each block to the contiguous 10-s block from the onset of seizure onward, in all cases. In seizures lasting >10 s (five cases), a supplementary analysis was performed, contrasting each block to a baseline condition, in the framework of the general linear model (GLM) of analysis. Regions of activations were compared to results from the different techniques performed during presurgical evaluation, such as SISCOM, positron emission tomography (PET), and invasive subdural EEG monitoring. KEY FINDINGS: Regarding the structural MRI findings, nine cases presented some lesion, with blood oxygen level- dependent (BOLD) signal activation placed in the same location in eight of them (89%). SISCOM studies were performed in 11 patients; 5 were concordant with the increase in BOLD signal in a sublobar level, whereas in 3 cases the concordance was in a lobar level. Eleven patients underwent PET studies, being also concordant in a sublobar level in four of them and in a lobar level in four additional cases. Finally, invasive EEG evaluation was performed in three patients and all of them had the seizure-onset zone in the initial area of BOLD activation. SIGNIFICANCE: This study adds relevant information to support the integration of EEG-fMRI in the multidisciplinary presurgical workup in patients with refractory epilepsy.

Functional neuroimaging in startle epilepsy: involvement of a mesial frontoparietal network.

PURPOSE: Startle epilepsy is a rare form of epilepsy with seizures triggered by unexpected stimuli. Previous studies have suggested the participation of several brain regions, such as the supplementary motor area (SMA) or the mesial aspect of the frontal and parietal lobes in the generation of startle epilepsy. However, how these brain regions interact with each other during seizures remains largely unknown. The aim of this study was to get insight into brain structures involved in startle-induced seizures using an approach with functional neuroimaging. METHODS: Four patients with startle epilepsy secondary to unexpected sounds were studied. All of them underwent a presurgical evaluation including ictal-single-emission computed tomography/subtraction ictal SPECT coregistered to MRI (magnetic resonance imaging) (SPECT/SISCOM). We searched for areas with ictal changes of perfusion higher than two standard deviations (2 SD) above the reference. In one patient, a fluorodeoxyglucose-positron emission tomography (FDG-PET) and an ictal electroencephalography-functional MRI (EEG-fMRI) were also performed. In this patient, the results of FDG-PET and sequential analysis of EEG-fMRI were compared to SISCOM. KEY FINDINGS: All the patients had their typical startle-induced seizures, consistent with bilateral asymmetric tonic seizures. Ictal-EEG pattern was located over the mesial centroparietal region in all of them. In three of four patients, a significant hyperperfusion over the mesial frontocentral region was seen, involving the SMA, the perirolandic region, and the precuneus. In one patient, who had a congenital bilateral perisylvian polymicrogyria, it was located over the lateral perirolandic region. 18F-FDG-PET results in the patient in whom it was done, were concordant with SISCOM findings. Ictal EEG-fMRI showed an initial activation located over the precuneus, SMA, cingulate gyrus, and the precentral/perirolandic area. SIGNIFICANCE: By using a functional neuroimaging approach we have found that startle-induced seizures could be generated by the interaction of a frontoparietal network located over the mesial surface of the brain.

Malignant autosomal dominant frontal lobe epilepsy with repeated episodes of status epilepticus: successful treatment with vagal nerve stimulation.

Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is a familial partial epilepsy syndrome characterized by seizures suggesting a frontal lobe origin occurring predominantly during sleep. Up to a third of patients may have refractory seizures, with repeated episodes of status epilepticus, intellectual disability of variable degree and psychiatric disturbances. We report a patient with ADNFLE, refractory seizures and repeated episodes of life-threatening convulsive status epilepticus who underwent prolonged video-EEG monitoring and was implanted with a vagal nerve stimulator. At 3.5 years of follow-up, a decrease of more than 80% in seizure frequency was achieved, episodes of status were completely controlled and he displayed improved mood and alertness. Vagal nerve stimulation may be considered as therapy for patients with refractory epilepsies of genetic cause, as well as repeated status epilepticus.

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

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

Sequential analysis of fMRI images: A new approach to study human epileptic networks.

PURPOSE: The aim of this study was to introduce a new approach for analysis of functional magnetic resonance imaging (fMRI) data in order to illustrate the temporal development of the blood oxygenation level-dependent (BOLD) signal changes induced by epileptic seizures. METHOD: In order to sequentially analyze the fMRI images acquired during epileptic seizures, a continuous series of echo planar imaging (EPI) scans covering the complete period of a seizure was acquired. Data were segmented into 10-s blocks. Each block, representing a unique experimental condition, was contrasted with a neutral (no seizure) baseline condition. Visual comparison of the activations from one block to the next highlighted the course of activations and deactivations during the seizure event. This analysis was applied to three independent seizures of one patient with peri-rolandic epilepsy secondary to chronic encephalitis: one seizure before epilepsy surgery and two after unsuccessful tailored resection. Observations were compared to results from invasive subdural electroencephalography (EEG) monitoring, single-photon emission computed tomography (SPECT) coregistered to MRI (SISCOM), and independent component analysis (ICA), a model-free method of BOLD-signal analysis. RESULTS: The initial increase in BOLD signal occurred 10-40 s before clinical onset in the same location compared to the seizure-onset zone determined by invasive subdural evaluation and SISCOM. Sequential involvement of cortical and subcortical structures was in agreement with SISCOM, intracranial EEG recordings, and ICA results. DISCUSSION: In selected patients, sequential analysis of changes in BOLD signal induced by epileptic seizures might represent a useful approach for investigating the temporal development of brain activity during epileptic seizures, thereby allowing imaging of those cerebral structures involved in seizure generation and propagation.

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

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

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

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

Oroalimentary automatisms induced by electrical stimulation of the fronto-opercular cortex in a patient without automotor seizures.

Despite being a common sign in focal epilepsies, the exact symptomatogenic zone for oroalimentary automatisms remains largely unknown. We describe a patient with refractory complex partial seizures secondary to a right temporoparietal malformation of cortical development who underwent prolonged video/EEG monitoring with subdural electrodes. During his typical seizures, the patient manifested decreased awareness but never automatisms. However, during electrical cortical stimulation of two electrodes located over the right inferior frontal gyrus, oroalimentary automatisms with preserved consciousness were elicited, with no afterdischarges detected in the adjacent electrodes. These two electrodes were distant from the seizure onset zone and were not involved in seizure propagation. This case provides evidence that fronto-opercular cortex may be involved in the generation of oroalimentary automatisms.

Pregabalin as add-on therapy for refractory partial seizures in every day clinical practice.

We retrospectively reviewed our clinical experience with PGB when used as add-on therapy in 101 patients (56 women and 45 men) with refractory partial epilepsy, who have been followed up for at least 1 year. Mean age was 40 years (16-64); mean number of concomitant AEDs was 2.8. Most patients (43) had temporal lobe epilepsy. Median number of seizures per month was 16 (3-240). Mean PGB dose used was 412.5 mg. Responder rate (percentage of patients with >or=50% seizure reduction) at 6 and 12 months was 52% and 39.6%, respectively. Seizure freedom for at least 6 and 12 months has been achieved by 12 patients (11.8%) and 6 patients (5.9%) respectively. At 1 year, 61 patients (60.4%) are still taking PGB. Forty patients have discontinued PGB, because of inefficacy (16 patients, 15.8%), adverse effects (15 patients, 14.8%) or both (9 patients, 8.9%). Sixty per cent of patients reported adverse events, being weight gain (>10% body weight) the most frequent, seen in 26 patients (25.7%). Dizziness/ataxia was seen in 20 (19.8%). Adverse effects were generally mild to moderate.

Presurgical evaluation in refractory epilepsy secondary to meningitis or encephalitis: bilateral memory deficits often preclude surgery.

We investigated the clinical features and surgical outcome of 17 patients with refractory epilepsy secondary to CNS infection who were referred to a tertiary center for presurgical evaluation. Six patients had a history of meningitis and 11 patients had a history of encephalitis. Median age at infection was three years (40 days-40 years). Time to seizure onset was shorter in the encephalitis group (median of 0.9 years versus 5.9 years in the meningitis group). MRI showed unilateral mesial temporal sclerosis (MTS) in all but one patient with meningitis (5/6). MRI in the encephalitis group showed unilateral MTS (four patients), bilateral MTS (three), porencephalic cysts (one) or no significant findings (three). Seizure semiology, following analysis of 127 seizures, included automotor seizures, complex motor/hypermotor seizures, dialeptic seizures and bilateral asymmetric tonic seizures. Neuropsychological assessment in patients with MTS frequently showed bilateral memory impairment (7 out of 12 MTS-patients), even in 4 patients with unilateral MTS, precluding epilepsy surgery. Six patients (two meningitis and four encephalitis patients) underwent a temporal lobe resection. All patients are either seizure-free (Class 1a) or are having only auras after surgery. One patient from the meningitis group underwent functional hemispherectomy and he is also seizure-free. In our series, MTS was the most common finding in refractory epilepsy after CNS infections. Bilateral memory deficits were often encountered in patients with MTS, even when unilateral, these deficits being a limiting factor for surgery. Good surgical outcome can be expected in selected patients with unilateral MTS and congruent memory deficits.

Early-onset absence epilepsy: clinical and electroencephalographic features in three children.

To describe the clinical and electroencephalographic features of three infants diagnosed as having early-onset absence seizures. Two males and one female, aged 21-29 months were seen in our neuropaediatric outpatient clinic because of daily episodes of motor arrest and loss of contact. Neurological examination and mental development was considered normal in all of them. Two out three had first-degree relatives with seizures with onset in the childhood and favourable evolution in the adulthood. A video-electroencephalogram was requested. Ictal EEG revealed a normal background and generalised spike-and-wave complexes at 3-3.5 Hz accompanied by disruption of ongoing activity in keeping with absence seizures. The duration of seizures ranged from 2 to 10s. One child (patient 2) experienced rhythmic myoclonic jerks in upper limbs and head as those described in myoclonic absences. Clinical and electroencephalographic follow-up ranged from 8 months to 4 years. Two children were on treatment with valproate and in the case of the patient 3, the combination of valproate and ethosuximide was necessary. Control of absence seizures was achieved in all our cases. Absence seizures should be considered as a possible cause of transient impairment of consciousness even among infants minor than 3 years of age. A video-electroencephalogram is the method of choice in the diagnostic evaluation and syndromic classification of these paroxysmal events.

Reversible motor and sensory peripheral neuropathy in a patient following acute carbon monoxide intoxication.

Central nervous system complications following carbon monoxide (CO) poisoning are well reported in the literature but peripheral neuropathy is under-recognized. We report the clinical and electrophysiological studies of the transient peripheral neuropathy developed in a patient following acute CO intoxication. A 27-year-old woman was found unconscious with severe hypoxia and 34.5% serum level of carboxyhemoglobin. She progressed favourably after hyperbaric oxygen therapy. Neurological examination revealed bilateral pyramidal signs. The patient referred weakness and sensory abnormalities in her right foot. An electroencephalogram did not show focal abnormalities and brain magnetic resonance was normal. Needle electromyography of weak right tibialis anterior muscle showed a reduced recruitment pattern but no spontaneous activity. Electroneurographic evaluation revealed findings compatible with a motor and sensory peripheral neuropathy in nerves of both lower limbs. In few months complete clinical recovery was reached, and the electroneurography showed normality a year later Reversible peripheral neuropathy should be considered as a possible neurological complication following acute CO poisoning. The electrophysiological studies were essential for its diagnosis and follow up.

Sporadic hyperekplexia presenting with an ataxic gait.

We describe a 62-year-old man with a sporadic form of hyperekplexia who presented with an unsteady gait, present since the age of 47. His clinical examination revealed an insecure broad-based gait and difficulty with tandem walking but no other abnormalities. For nearly a decade the patient was misdiagnosed with an idiopathic ataxia. A video electroencephalogram combined with an electromyogram during sudden auditory stimulus demonstrated an excessive startle response. An extensive work-up ruled out all the known causes of symptomatic hyperekplexia including anti-glycine receptor antibodies. Treatment with clonazepam markedly reduced the threshold and intensity of the startle response, enabling him to recover independence. Hyperekplexia is frequently associated with an awkward and hesitating gait, but these gait abnormalities might be confused with other causes of gait disorders if one is not aware of this disease. We report this patient to highlight that a correct diagnosis of hyperekplexia is crucial, because its treatment may change quality of life.

Seizure frequency and social outcome in drug resistant epilepsy patients who do not undergo epilepsy surgery.

Little is known about the long term prognosis of refractory epilepsy patients who do not undergo epilepsy surgery. We performed a telephone survey and chart review of patients who underwent presurgical evaluation in our Unit but did not have surgery, from 1998 until 2004. We contacted 84 patients; mean follow-up was 6.7 years. Four patients (4.7%) had died, presumably of SUDEP. Ten patients (13.1%) were seizure free. In most patients with seizures, frequency remained stable (24/80, 30%) or had decreased by ≥50% (26 patients, 30.9%). Most patients (69, 86.2%) believed their health was similar or better respect to the moment they underwent presurgical evaluation. Employment situation was stable in 64/80 patients (80%), but 11 had received new disability wages. Family situation was also generally unchanged (69/80 patients, 86.2%). Most patients were not taking antidepressants. Seizure free patients scored higher in satisfaction with life. This information can be used to counsel refractory patients.

Use of levetiracetam in hospitalized patients.

PURPOSE: The objective of the study was to analyze the short-term efficacy and safety of levetiracetam (LEV) to treat repetitive seizures in hospitalized patients. METHODS: During admission to a tertiary hospital, we retrospectively identified patients with repetitive seizures who were treated for the first time with LEV during a hospital stay. LEV was considered effective if seizure cessation or >75% seizure reduction occurred in the 24 h after starting LEV (compared with the previous 48 h), requiring no further antiepileptic drug (AED) treatment. RESULTS: Thirty patients (12 men, 18 women) were included. Mean age was 59.7 years. Most frequent seizure type was focal motor in 12 (40%) of 30 patients. Most frequent etiology was stroke: nine (30%) of 30 patients. Relevant medical conditions included atrial fibrillation (three) and hepatic disease (three). Concomitant medications included oral anticoagulants (seven), corticosteroids (two), and chemotherapy (two). Four patients received LEV as the only AED. Six patients with focal SE and 20 (66.6%) patients with clusters of seizures but not in SE received LEV as add-on treatment after lack of response to first-line AEDs. Mean LEV dose during first day was 1,119 mg. Mean daily maintenance dose was 1,724 mg. LEV was effective in 24 (80%) patients, all four patients who received it as the only AED, four of six patients with focal SE, and 16 of 20 patients with clusters of seizures. Three (10%) elderly patients with seizures secondary to stroke and chronic obstructive pulmonary disease (COPD) reported moderate/severe somnolence and dizziness, leading to treatment discontinuation in one. On discharge, 20 (66.7%) patients continued on LEV, nine (30%) as the only AED. CONCLUSIONS: LEV is effective and safe to treat repetitive seizures in hospitalized patients, including patients in focal SE.