RESEARCH HIGHLIGHTS Nature Reviews Neurology 10, 363 (2014); published online 17 June 2014; doi:10.1038/nrneurol.2014.106
EPILEPSY
Electrophysiology elucidates epileptiform activity
S
uccessfully treating patients with recurring seizures requires a clear understanding of the underlying disorder. Two recently published studies have demonstrated how electromyography (EMG) and stereo-EEG can facilitate the diagnosis and localization of epileptic seizures. Sándor Beniczky and colleagues were motivated by the challenge of differentially diagnosing seizure disorders. “Patients with psychogenic nonepileptic convulsive seizures are often unnecessarily treated with high dose of antiepileptic drugs in emergency departments,” explains Beniczky. “Differentiation from epileptic convulsive seizures requires special expertise and long-term video– EEG monitoring, which is extremely resource-demanding.” Previous work has suggested that during generalized tonic–clonic seizures, which are unique to epilepsy, both the amplitude and frequency components of surface EMG recordings have a distinct pattern. To assess whether muscle activation could differentiate seizure aetiologies, Beniczky et al. analysed recordings from 25 patients consecutively admitted to an epilepsy clinic, and compared the diagnostic sensitivity of shoulder EMG recordings and video–EEG monitoring—the current gold-standard. No single EMG measure was able to reliably distinguish individual seizures, but combined analysis of amplitudes, the ratio of high-frequency versus lowfrequency wavelets, and the presence of ‘silent’ periods without EMG activity identified generalized tonic–clonic seizures with 100% concordance to video–EEG monitoring. Additionally, by examining EMG data from healthy controls attempting to imitate tonic–clonic seizures, the authors discovered that psychogenic nonepileptic seizures are not simply mimed convulsions, but rather are associated with their own distinct pattern of muscle activation. These data suggest that it is possible to accurately diagnose epileptic seizures with
Electromyographic data from a generalized tonic–clonic seizure (top) and a psychogenic non-epileptic seizure (bottom). Image courtesy of Sándor Beniczky.
less-intensive monitoring than the current best practice; however, follow-up testing will be necessary to address whether EMG-based diagnoses are feasible in routine clinical assessment. “We have developed a portable device that analyses surface EMG signals in realtime to distinguish between generalised tonic–clonic seizures and psychogenic nonepileptic convulsive seizures,” says Beniczky. “At present, we are conducting a multicentre, prospective, blinded validation study of this device.” The standard care for patients with epilepsy is treatment with antiepileptic medications, but some patients do not respond to these drugs. One treatment option for these refractory patients is resective surgery, where the epileptic focus is lesioned in the hopes of eliminating or attenuating future seizures. The success of this technique is predicated on accurate localization of the focus, usually based on recordings from grid or strip electrodes implanted below the dura mater. “Despite the high spatial resolution provided by subdural electrodes, relatively deep epileptic foci cannot be localized with adequate spatial and temporal resolution,” says the lead investigator Jorge Gonzalez-Martinez. “In addition, subdural grids require large craniotomies and are generally limited to the exploration of one hemisphere,” which limits the use of these electrodes in some paediatric patients. Gonzalez-Martinez and colleagues implanted stereo-EEG electrodes in the skulls of 30 paediatric patients whose
NATURE REVIEWS | NEUROLOGY
epileptic foci had proven difficult to localize by other means. Stereo-EEG monitoring revealed the epileptic foci in all but four patients, and the complication rate in the 30 days after implantation was only 3%. Resective surgery was performed in 18 of these patients: at the end of the follow-up (12–47 months), 10 patients were seizure-free and five had markedly reduced seizure severity. “The stereo-EEG methodology is safe, and should be considered in children and adolescents with difficult to localize epilepsy,” concludes Gonzalez-Martinez. The authors are currently planning a clinical trial that directly compares presurgical monitoring via stereo-EEG or subdural electrodes with noninvasive focus-localization, for example by single-photon emission CT or PET brain imaging. The authors hope that these data will bring us closer to finding an effective and minimally invasive technique for recording and localizing epileptiform brain activity. Such a technique has the potential not only to improve outcomes for resective surgery, but also to reveal new targets for deep brain stimulation in refractory focal epilepsy. Alex Chase Original articles Beniczky, S. et al. Quantitative analysis of surface electromyography during epileptic and nonepileptic convulsive seizures. Epilepsia doi:10.1111/ epi.12669 | Gonzalez-Martinez, J. et al. SEEG in children and adolescents with “difficult to localize” refractory focal epilepsy. Neurosurgery doi:10.1227/ NEU.0000000000000453
VOLUME 10 | JULY 2014 © 2014 Macmillan Publishers Limited. All rights reserved
EPILEPSY
Electrophysiology elucidates epileptiform activity
S
uccessfully treating patients with recurring seizures requires a clear understanding of the underlying disorder. Two recently published studies have demonstrated how electromyography (EMG) and stereo-EEG can facilitate the diagnosis and localization of epileptic seizures. Sándor Beniczky and colleagues were motivated by the challenge of differentially diagnosing seizure disorders. “Patients with psychogenic nonepileptic convulsive seizures are often unnecessarily treated with high dose of antiepileptic drugs in emergency departments,” explains Beniczky. “Differentiation from epileptic convulsive seizures requires special expertise and long-term video– EEG monitoring, which is extremely resource-demanding.” Previous work has suggested that during generalized tonic–clonic seizures, which are unique to epilepsy, both the amplitude and frequency components of surface EMG recordings have a distinct pattern. To assess whether muscle activation could differentiate seizure aetiologies, Beniczky et al. analysed recordings from 25 patients consecutively admitted to an epilepsy clinic, and compared the diagnostic sensitivity of shoulder EMG recordings and video–EEG monitoring—the current gold-standard. No single EMG measure was able to reliably distinguish individual seizures, but combined analysis of amplitudes, the ratio of high-frequency versus lowfrequency wavelets, and the presence of ‘silent’ periods without EMG activity identified generalized tonic–clonic seizures with 100% concordance to video–EEG monitoring. Additionally, by examining EMG data from healthy controls attempting to imitate tonic–clonic seizures, the authors discovered that psychogenic nonepileptic seizures are not simply mimed convulsions, but rather are associated with their own distinct pattern of muscle activation. These data suggest that it is possible to accurately diagnose epileptic seizures with
Electromyographic data from a generalized tonic–clonic seizure (top) and a psychogenic non-epileptic seizure (bottom). Image courtesy of Sándor Beniczky.
less-intensive monitoring than the current best practice; however, follow-up testing will be necessary to address whether EMG-based diagnoses are feasible in routine clinical assessment. “We have developed a portable device that analyses surface EMG signals in realtime to distinguish between generalised tonic–clonic seizures and psychogenic nonepileptic convulsive seizures,” says Beniczky. “At present, we are conducting a multicentre, prospective, blinded validation study of this device.” The standard care for patients with epilepsy is treatment with antiepileptic medications, but some patients do not respond to these drugs. One treatment option for these refractory patients is resective surgery, where the epileptic focus is lesioned in the hopes of eliminating or attenuating future seizures. The success of this technique is predicated on accurate localization of the focus, usually based on recordings from grid or strip electrodes implanted below the dura mater. “Despite the high spatial resolution provided by subdural electrodes, relatively deep epileptic foci cannot be localized with adequate spatial and temporal resolution,” says the lead investigator Jorge Gonzalez-Martinez. “In addition, subdural grids require large craniotomies and are generally limited to the exploration of one hemisphere,” which limits the use of these electrodes in some paediatric patients. Gonzalez-Martinez and colleagues implanted stereo-EEG electrodes in the skulls of 30 paediatric patients whose
NATURE REVIEWS | NEUROLOGY
epileptic foci had proven difficult to localize by other means. Stereo-EEG monitoring revealed the epileptic foci in all but four patients, and the complication rate in the 30 days after implantation was only 3%. Resective surgery was performed in 18 of these patients: at the end of the follow-up (12–47 months), 10 patients were seizure-free and five had markedly reduced seizure severity. “The stereo-EEG methodology is safe, and should be considered in children and adolescents with difficult to localize epilepsy,” concludes Gonzalez-Martinez. The authors are currently planning a clinical trial that directly compares presurgical monitoring via stereo-EEG or subdural electrodes with noninvasive focus-localization, for example by single-photon emission CT or PET brain imaging. The authors hope that these data will bring us closer to finding an effective and minimally invasive technique for recording and localizing epileptiform brain activity. Such a technique has the potential not only to improve outcomes for resective surgery, but also to reveal new targets for deep brain stimulation in refractory focal epilepsy. Alex Chase Original articles Beniczky, S. et al. Quantitative analysis of surface electromyography during epileptic and nonepileptic convulsive seizures. Epilepsia doi:10.1111/ epi.12669 | Gonzalez-Martinez, J. et al. SEEG in children and adolescents with “difficult to localize” refractory focal epilepsy. Neurosurgery doi:10.1227/ NEU.0000000000000453
VOLUME 10 | JULY 2014 © 2014 Macmillan Publishers Limited. All rights reserved
