Epilepsy affects all age groups and is one of the most common and most disabling neurological disorders. The accurate diagnosis of seizures is essential as some patients will be misdiagnosed with epilepsy, whereas others will receive an incorrect diagnosis. Indeed, errors in diagnosis are common, and many patients fail to receive the correct treatment, which often has severe consequences. Although many patients have seizure control using a single medication, others require multiple medications, resective surgery, neuromodulation devices or dietary therapies. In addition, one-third of patients will continue to have uncontrolled seizures. Epilepsy can substantially impair quality of life owing to seizures, comorbid mood and psychiatric disorders, cognitive deficits and adverse effects of medications. In addition, seizures can be fatal owing to direct effects on autonomic and arousal functions or owing to indirect effects such as drowning and other accidents. Deciphering the pathophysiology of epilepsy has advanced the understanding of the cellular and molecular events initiated by pathogenetic insults that transform normal circuits into epileptic circuits (epileptogenesis) and the mechanisms that generate seizures (ictogenesis). The discovery of >500 genes associated with epilepsy has led to new animal models, more precise diagnoses and, in some cases, targeted therapies.

Because seizures originate from different pathological substrates, the question arises of whether distinct or similar mechanisms underlie seizure generation across different pathologies. Better defining intracranial electroencephalographic morphological patterns at seizure-onset could improve the understanding of such mechanisms. To this end, we investigated intracranial electroencephalographic seizure-onset patterns associated with different epileptogenic lesions, and defined high-frequency oscillation correlates of each pattern. We analysed representative seizure types from 33 consecutive patients with drug-resistant focal epilepsy and a structural magnetic resonance imaging lesion (11 mesial temporal sclerosis, nine focal cortical dysplasia, six cortical atrophy, three periventricular nodular heterotopia, three polymicrogyria, and one tuberous sclerosis complex) who underwent depth-electrode electroencephalographic recordings (500 Hz filter, 2000 Hz sampling rate). Patients were included only if seizures arose from contacts located in lesional/peri-lesional tissue, and if clinical manifestations followed the electrographic onset. Seizure-onset patterns were defined independently by two reviewers blinded to clinical information, and consensus was reached after discussion. For each seizure, pre-ictal and ictal sections were selected for high-frequency oscillation analysis. Seven seizure-onset patterns were identified across the 53 seizures sampled: low-voltage fast activity (43%); low-frequency high-amplitude periodic spikes (21%); sharp activity at ≤13 Hz (15%); spike-and-wave activity (9%); burst of high-amplitude polyspikes (6%); burst suppression (4%); and delta brush (4%). Each pattern occurred across several pathologies, except for periodic spikes, only observed with mesial temporal sclerosis, and delta brush, exclusive to focal cortical dysplasia. However, mesial temporal sclerosis was not always associated with periodic spikes nor focal cortical dysplasia with delta brush. Compared to other patterns, low-voltage fast activity was associated with a larger seizure-onset zone (P = 0.04). Four patterns, sharp activity at ≤13 Hz, low-voltage fast activity, spike-and-wave activity and periodic spikes, were also found in regions of seizure spread, with periodic spikes only emerging from mesial temporal sclerosis. Each of the seven patterns was accompanied by a significant increase in high-frequency oscillations upon seizure-onset. Overall, our data indicate that: (i) biologically-distinct epileptogenic lesions share intracranial electroencephalographic seizure-onset patterns, suggesting that different pathological substrates can affect similarly networks or mechanisms underlying seizure generation; (ii) certain pathologies are associated with intracranial electroencephalographic signatures at seizure-onset, e.g. periodic spikes which may reflect mechanisms specific to mesial temporal sclerosis; (iii) some seizure-onset patterns, including periodic spikes, can also be found in regions of spread, which cautions a...

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High-fidelity intracranial electrode arrays for recording and stimulating brain activity have facilitated major advances in the treatment of neurological conditions over the past decade. Traditional arrays require direct implantation into the brain via open craniotomy, which can lead to inflammatory tissue responses, necessitating development of minimally invasive approaches that avoid brain trauma. Here we demonstrate the feasibility of chronically recording brain activity from within a vein using a passive stent-electrode recording array (stentrode). We achieved implantation into a superficial cortical vein overlying the motor cortex via catheter angiography and demonstrate neural recordings in freely moving sheep for up to 190 d. Spectral content and bandwidth of vascular electrocorticography were comparable to those of recordings from epidural surface arrays. Venous internal lumen patency was maintained for the duration of implantation. Stentrodes may have wide ranging applications as a neural interface for treatment of a range of neurological conditions.

SUMMARYPurpose: Removal of areas generating high-frequency oscillations (HFOs) recorded from the intracerebral electroencephalography (iEEG) of patients with medically intractable epilepsy has been found to be correlated with improved surgical outcome. However, whether differences exist according to the type of epilepsy is largely unknown. We performed a comparative assessment of the impact of removing HFO-generating tissue on surgical outcome between temporal lobe epilepsy (TLE) and extratemporal lobe epilepsy (ETLE). We also assessed the relationship between the extent of surgical resection and surgical outcome. Methods: We studied 30 patients with drug-resistant focal epilepsy, 21 with TLE and 9 with ETLE. Two thirds of the patients were included in a previous report and for these, clinical and imaging data were updated and followup was extended. All patients underwent iEEG investigations (500 Hz high-pass filter and 2,000 Hz sampling rate), surgical resection, and postoperative magnetic resonance imaging (MRI). HFOs (ripples, 80-250 Hz; fast ripples, >250 Hz) were identified visually on a 5-10 min interictal iEEG sample. HFO rates inside versus outside the seizure-onset zone (SOZ), in resected versus nonresected tissue, and their association with surgical outcome (ILAE classification) were assessed in the entire cohort, and in the TLE and ETLE subgroups. We also tested the correlation of resected brain hippocampal and amygdala volumes (as measured on postoperative MRIs) with surgical outcome. Key Findings: HFO rates were significantly higher inside the SOZ than outside in the entire cohort and TLE subgroup, but not in the ETLE subgroup. In all groups, HFO rates did not differ significantly between resected and nonresected tissue. Surgical outcome was better when higher HFO rates were included in the surgical resection in the entire cohort and TLE subgroup, but not in the ETLE subgroup. Resected brain hippocampal and amygdala volumes were not correlated with surgical outcome. Significance: In TLE, removal of HFO-generating areas may lead to improved surgical outcome. Less consistent findings emerge from ETLE, but these may be related to sample size limitations of this study. Size of resection, a factor that was ignored and that could have affected results of earlier studies did not influence results.

SUMMARYPurpose: Despite the widespread use of antiepileptic drugs (AEDs) across different neurologic and psychiatric disorders, no study has systematically reviewed all available randomized controlled trials (RCTs) of a given AED to fully uncover its tolerability profile. We aimed at identifying treatment emergent adverse events (AEs) associated with pregabalin through a systematic review and meta-analysis of all available RCTs. We also assessed the association between serious AEs and pregabalin, and investigated whether pregabalin AEs display a dose-response relationship. Methods: We searched MEDLINE, EMBASE, and Cochrane CENTRAL to February 2010 for RCTs. Additional studies were identified from reference lists of retrieved papers and from online clinical databases. We selected placebocontrolled, double-blind RCTs investigating the therapeutic effects of pregabalin in adults with any condition. Studies had to include at least 20 subjects per arm and have a duration of at least 4 weeks. AEs were assessed for their association with pregabalin after identification/ exclusion of synonyms, rare AEs, and nonassessable AEs due to methodologic limitations. We used relative risks (RRs) to assess the association of any [99% confidence intervals (CIs)] or serious AEs (95% CIs) with pregabalin, and risk differences (RDs, 95% CIs) to investigate doseresponse relationships of pregabalin AEs. Key findings: Thirty-eight RCTs were included in our study. Of 39 AEs, 20 (51%) were significantly associated with pregabalin (dizziness, vertigo, incoordination, balance disorder, ataxia, diplopia, blurred vision, amblyopia, tremor, somnolence, confusional state, disturbance in attention, thinking abnormal, euphoria, asthenia, fatigue, edema, peripheral edema, dry mouth, constipation). The highest RRs were found for cognition/coordination AEs. There was no significant association between serious AEs and pregabalin. There was a selective dose-response pattern in the onset of pregabalin AEs, with certain AEs appearing at lower doses than others. Significance: Individuals starting treatment with pregabalin are at increased risk for several AEs, particularly those affecting cognition/coordination. Pregabalin AEs appear according to a selective dose-response pattern, possibly reflecting the severity of dysfunction of distinct anatomic structures. These findings may aid clinicians in providing better patient management, and support the value of including in meta-analyses of AED tolerability profiles RCTs performed in different conditions.

Background: Adverse effects (AEs) of antiepileptic drugs (AEDs) are a major impediment to opti-

On an individual patient level, a prediction of outcome was not possible in all patients. This may be due to the analysis techniques used. Alternatively, HFOs may be less specific for epileptic tissue than earlier studies have indicated.