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The pre-ictal state in focal epilepsy
Comment
The pre-ictal state in focal epilepsy
www.thelancet.com Vol 366 December 17/24/31, 2005
resulting in a decreased BOLD signal and suppressed preictal neuronal activity in the seizure onset zone. In the third patient, the pre-ictal BOLD signal increased in the left premotor/prefrontal area, and in the left caudate was co-localised with the sites of hyperperfusion seen on ictal single-photon emission CT. These changes, however, were contralateral to seizure focus localisation with clinical seizure semiology. Federico and colleagues speculated that this patient had seizures arising from the supplementary sensorimotor area, resulting in ipsilateral motor symptoms, and that the BOLD signal increases represented involvement of a complex cortical and subcortical network. Federico and colleagues’ paper provides important insight into the mechanisms underlying the transition from the interictal to the ictal state and further documents the existence of a pre-ictal state with circumscribed BOLD fMRI changes occurring several minutes before the actual seizure onset. These BOLD changes can be localised to the seizure-onset zone, but also to distant brain regions reflecting active inhibitory processes. The process of ictogenesis therefore probably takes place over minutes or hours before the actual seizure, and involves a spatially distributed neuronal network with a complex interplay of excitatory and inhibitory processes. The next logical step is to correlate these BOLD fMRI changes with the results of advanced EEG analysis.1,2 These techniques suggest a cascade of complex events taking place over hours and requiring coincident activation and deactivation of several brain regions—cortical, subcortical, or both—to generate
Rights were not granted to include this image in electronic media. Please refer to the printed journal Science Photo Library
The mechanisms underlying the transition from the interictal to the ictal state in human focal epilepsy are poorly understood. Various techniques, including nonlinear and linear electroencephalogram (EEG) analysis,1,2 single-photon emission CT,3 and invasive long-term monitoring of cortical cerebral blood flow,4 have identified a pre-ictal state several minutes to hours before a seizure. This pre-ictal state can be distinguished from the interictal and ictal states, and might be the key to a better understanding about the transition to seizures. Recently, Paolo Federico and colleagues5 reported their functional MRI (fMRI) analysis of the pre-ictal state in three patients with intractable focal epilepsy. With BOLD (blood-oxygen-level dependent) measurements, all patients showed large pre-ictal signal changes several minutes before the seizure. The first patient had a striking increase in pre-ictal BOLD signal in the region of the seizure focus, with no significant BOLD signal changes in other regions. This finding agrees with a previous study that used pre-ictal single-photon emission CT in two patients with temporal lobe epilepsy under continuous video-EEG monitoring. That study showed a significant increase in regional cerebral blood flow in the epileptic temporal lobe 11–12 min before the seizure.3 Several studies with long-term surface cortical-cerebral blood-flow monitoring with subdural thermal-diffusion flowmetry cerebral blood flow probes,4,6 and laser-doppler probes attached to custom-made subdural electrodes7,8 reported a significant increase in cerebral blood flow in the epileptic temporal lobe 10–20 min before the seizure, while cerebral blood flow in the contralateral temporal lobe either decreased or only slightly increased. Furthermore, two fMRI studies found a pre-ictal BOLD increase in the seizure-onset zone in a boy with Rasmussen’s encephalitis9 and a woman with a small right-central malignant glioma.10 The second patient showed pre-ictal BOLD signal decreases near the presumed seizure focus, and there was a widespread increase in pre-ictal BOLD signal over the contralateral hemisphere. Federico and colleagues suggested that the increase in contralateral BOLD signal represented an increase in overall synaptic activity at sites with inhibitory projections to the seizure focus, and therefore might reflect an active inhibitory process
EEG examination
2065
Comment
seizures.1 The most important question, however, will be how these pre-ictal BOLD changes translate into actual changes in neuronal activity or whether they reflect other processes such as glial, ionic, or neurovascular changes, which are responsible for, or at least facilitate the process of, the transition to seizures. However, BOLD signal changes and their relations to excitatory and inhibitory processes are complex.11 Eventually, a better understanding of the pre-ictal state may help development of closed-loop seizure warning and treatment devices, which could apply electrical stimulation or focal drug delivery on demand and therefore might be more effective, and associated with fewer side-effects, than present antiepileptic drugs. *Christoph Baumgartner, Susanne Aull-Watschinger Department of Clinical Neurology, Medical University of Vienna, A-1090 Vienna, Austria [email protected] We declare that we have no conflict of interest.
1
Litt B, Echauz J. Prediction of epileptic seizures. Lancet Neurol 2002; 1: 22–30. 2 Lehnertz K, Mormann F, Kreuz T, et al. Seizure prediction by nonlinear EEG analysis. IEEE Eng Med Biol Mag 2003; 22: 57–63. 3 Baumgartner C, Serles W, Leutmezer F, et al. Preictal SPECT in temporal lobe epilepsy: regional cerebral blood flow is increased prior to electroencephalography-seizure onset. J Nucl Med 1998; 39: 978–82. 4 Weinand ME, Carter LP, el-Saadany WF, Sioutos PJ, Labiner DM, Oommen KJ. Cerebral blood flow and temporal lobe epileptogenicity. J Neurosurg 1997; 86: 226–32. 5 Federico P, Abbott DF, Briellmann RS, Harvey AS, Jackson GD. Functional MRI of the pre-ictal state. Brain 2005; 128: 1811–17. 6 Weinand ME, Carter LP, Patton DD, Oommen KJ, Labiner DM, Talwar D. Long-term surface cortical cerebral blood flow monitoring in temporal lobe epilepsy. Neurosurgery 1994; 35: 657–64. 7 Gazelius B, Lind G, Meyerson BA, Linderoth B. Chronic multifocal recording of cortical microcirculation and subdural EEG during epileptic seizures in humans. Epilepsia 1995; 36 (suppl 3): S146–47. 8 Wallstedt L, Gazelius B, Hellstrand E, Linderoth B, Amark P. Cortical microcirculation during epileptic seizures: temporo-spatial relations to ictal onset and focus. Epilepsia 1996; 37 (suppl 4): 163. 9 Jackson GD, Connelly A, Cross JH, Gordon I, Gadian DG. Functional magnetic resonance imaging of focal seizures. Neurology 1994; 44: 850–56. 10 Krings T, Topper R, Reinges MH, et al. Hemodynamic changes in simple partial epilepsy: a functional MRI study. Neurology 2000; 54: 524–27. 11 Logothetis NK, Pauls J, Augath M, Trinath T, Oeltermann A. Neurophysiological investigation of the basis of the fMRI signal. Nature 2001; 412: 150–57.
Psychosocial aid to children after the Dec 26 tsunami The Dec 26, 2004, tsunami had profound effects on children, who have unique vulnerabilities, needs, and strengths. The tsunami ravaged children’s sense of safety and predictability, and increased their vulnerability. Many of the children involved feared for their lives or narrowly escaped death, and many suffered the loss of parents, siblings, friends, and neighbours. The tsunami destroyed children’s social supports by devastating homes, schools, and communities, and overwhelming the adults caring for them. Adding to children’s risks were ongoing threats to their protection, such as separation from parents, sexual exploitation, trafficking, recruitment into armed groups, and dangerous labour. Previous research and our observations indicate that most children experiencing disasters, conflict, and other traumatic events have mild to moderate levels of distress but remain functional.1,2 Typically, less than 15% of a disaster-affected population express mental disorders that require intensive mental-health care.3 What most children need is not therapy but communitybased activities that help to restore their sense of safety, connection to caring adults, and hope for the future.1,2 2066
To support children, Christian Children’s Fund, working with local partners, established 240 childcentred spaces in tsunami-affected areas of Sri Lanka, India, and Indonesia, involving more than 38 000 children from birth to 18 years of age. In open areas or in new or existing structures, these spaces provide rapid psychosocial support by engaging children in activities that aim to restore a sense of safety and predictability, enable emotional expression, address health risks, and foster social integration.4 The staff are local community volunteers, including teachers and youth workers, who are trained and supported by specialists in child protection. Previously, child-centred spaces have been started by the Christian Children’s Fund in conflict and postconflict situations in Afghanistan, Angola, Sierra Leone, Kosovo, and East Timor, where the scale and nature of the devastation have affected children.5 Activities in the children’s centres aim to help to restore young children’s sense of safety by providing a safe place where they can play surrounded by caring adults whom they trust. The centres try to restore children’s sense of normalcy and predictability through structured activities such as singing and dancing, www.thelancet.com Vol 366 December 17/24/31, 2005
The pre-ictal state in focal epilepsy
www.thelancet.com Vol 366 December 17/24/31, 2005
resulting in a decreased BOLD signal and suppressed preictal neuronal activity in the seizure onset zone. In the third patient, the pre-ictal BOLD signal increased in the left premotor/prefrontal area, and in the left caudate was co-localised with the sites of hyperperfusion seen on ictal single-photon emission CT. These changes, however, were contralateral to seizure focus localisation with clinical seizure semiology. Federico and colleagues speculated that this patient had seizures arising from the supplementary sensorimotor area, resulting in ipsilateral motor symptoms, and that the BOLD signal increases represented involvement of a complex cortical and subcortical network. Federico and colleagues’ paper provides important insight into the mechanisms underlying the transition from the interictal to the ictal state and further documents the existence of a pre-ictal state with circumscribed BOLD fMRI changes occurring several minutes before the actual seizure onset. These BOLD changes can be localised to the seizure-onset zone, but also to distant brain regions reflecting active inhibitory processes. The process of ictogenesis therefore probably takes place over minutes or hours before the actual seizure, and involves a spatially distributed neuronal network with a complex interplay of excitatory and inhibitory processes. The next logical step is to correlate these BOLD fMRI changes with the results of advanced EEG analysis.1,2 These techniques suggest a cascade of complex events taking place over hours and requiring coincident activation and deactivation of several brain regions—cortical, subcortical, or both—to generate
Rights were not granted to include this image in electronic media. Please refer to the printed journal Science Photo Library
The mechanisms underlying the transition from the interictal to the ictal state in human focal epilepsy are poorly understood. Various techniques, including nonlinear and linear electroencephalogram (EEG) analysis,1,2 single-photon emission CT,3 and invasive long-term monitoring of cortical cerebral blood flow,4 have identified a pre-ictal state several minutes to hours before a seizure. This pre-ictal state can be distinguished from the interictal and ictal states, and might be the key to a better understanding about the transition to seizures. Recently, Paolo Federico and colleagues5 reported their functional MRI (fMRI) analysis of the pre-ictal state in three patients with intractable focal epilepsy. With BOLD (blood-oxygen-level dependent) measurements, all patients showed large pre-ictal signal changes several minutes before the seizure. The first patient had a striking increase in pre-ictal BOLD signal in the region of the seizure focus, with no significant BOLD signal changes in other regions. This finding agrees with a previous study that used pre-ictal single-photon emission CT in two patients with temporal lobe epilepsy under continuous video-EEG monitoring. That study showed a significant increase in regional cerebral blood flow in the epileptic temporal lobe 11–12 min before the seizure.3 Several studies with long-term surface cortical-cerebral blood-flow monitoring with subdural thermal-diffusion flowmetry cerebral blood flow probes,4,6 and laser-doppler probes attached to custom-made subdural electrodes7,8 reported a significant increase in cerebral blood flow in the epileptic temporal lobe 10–20 min before the seizure, while cerebral blood flow in the contralateral temporal lobe either decreased or only slightly increased. Furthermore, two fMRI studies found a pre-ictal BOLD increase in the seizure-onset zone in a boy with Rasmussen’s encephalitis9 and a woman with a small right-central malignant glioma.10 The second patient showed pre-ictal BOLD signal decreases near the presumed seizure focus, and there was a widespread increase in pre-ictal BOLD signal over the contralateral hemisphere. Federico and colleagues suggested that the increase in contralateral BOLD signal represented an increase in overall synaptic activity at sites with inhibitory projections to the seizure focus, and therefore might reflect an active inhibitory process
EEG examination
2065
Comment
seizures.1 The most important question, however, will be how these pre-ictal BOLD changes translate into actual changes in neuronal activity or whether they reflect other processes such as glial, ionic, or neurovascular changes, which are responsible for, or at least facilitate the process of, the transition to seizures. However, BOLD signal changes and their relations to excitatory and inhibitory processes are complex.11 Eventually, a better understanding of the pre-ictal state may help development of closed-loop seizure warning and treatment devices, which could apply electrical stimulation or focal drug delivery on demand and therefore might be more effective, and associated with fewer side-effects, than present antiepileptic drugs. *Christoph Baumgartner, Susanne Aull-Watschinger Department of Clinical Neurology, Medical University of Vienna, A-1090 Vienna, Austria [email protected] We declare that we have no conflict of interest.
1
Litt B, Echauz J. Prediction of epileptic seizures. Lancet Neurol 2002; 1: 22–30. 2 Lehnertz K, Mormann F, Kreuz T, et al. Seizure prediction by nonlinear EEG analysis. IEEE Eng Med Biol Mag 2003; 22: 57–63. 3 Baumgartner C, Serles W, Leutmezer F, et al. Preictal SPECT in temporal lobe epilepsy: regional cerebral blood flow is increased prior to electroencephalography-seizure onset. J Nucl Med 1998; 39: 978–82. 4 Weinand ME, Carter LP, el-Saadany WF, Sioutos PJ, Labiner DM, Oommen KJ. Cerebral blood flow and temporal lobe epileptogenicity. J Neurosurg 1997; 86: 226–32. 5 Federico P, Abbott DF, Briellmann RS, Harvey AS, Jackson GD. Functional MRI of the pre-ictal state. Brain 2005; 128: 1811–17. 6 Weinand ME, Carter LP, Patton DD, Oommen KJ, Labiner DM, Talwar D. Long-term surface cortical cerebral blood flow monitoring in temporal lobe epilepsy. Neurosurgery 1994; 35: 657–64. 7 Gazelius B, Lind G, Meyerson BA, Linderoth B. Chronic multifocal recording of cortical microcirculation and subdural EEG during epileptic seizures in humans. Epilepsia 1995; 36 (suppl 3): S146–47. 8 Wallstedt L, Gazelius B, Hellstrand E, Linderoth B, Amark P. Cortical microcirculation during epileptic seizures: temporo-spatial relations to ictal onset and focus. Epilepsia 1996; 37 (suppl 4): 163. 9 Jackson GD, Connelly A, Cross JH, Gordon I, Gadian DG. Functional magnetic resonance imaging of focal seizures. Neurology 1994; 44: 850–56. 10 Krings T, Topper R, Reinges MH, et al. Hemodynamic changes in simple partial epilepsy: a functional MRI study. Neurology 2000; 54: 524–27. 11 Logothetis NK, Pauls J, Augath M, Trinath T, Oeltermann A. Neurophysiological investigation of the basis of the fMRI signal. Nature 2001; 412: 150–57.
Psychosocial aid to children after the Dec 26 tsunami The Dec 26, 2004, tsunami had profound effects on children, who have unique vulnerabilities, needs, and strengths. The tsunami ravaged children’s sense of safety and predictability, and increased their vulnerability. Many of the children involved feared for their lives or narrowly escaped death, and many suffered the loss of parents, siblings, friends, and neighbours. The tsunami destroyed children’s social supports by devastating homes, schools, and communities, and overwhelming the adults caring for them. Adding to children’s risks were ongoing threats to their protection, such as separation from parents, sexual exploitation, trafficking, recruitment into armed groups, and dangerous labour. Previous research and our observations indicate that most children experiencing disasters, conflict, and other traumatic events have mild to moderate levels of distress but remain functional.1,2 Typically, less than 15% of a disaster-affected population express mental disorders that require intensive mental-health care.3 What most children need is not therapy but communitybased activities that help to restore their sense of safety, connection to caring adults, and hope for the future.1,2 2066
To support children, Christian Children’s Fund, working with local partners, established 240 childcentred spaces in tsunami-affected areas of Sri Lanka, India, and Indonesia, involving more than 38 000 children from birth to 18 years of age. In open areas or in new or existing structures, these spaces provide rapid psychosocial support by engaging children in activities that aim to restore a sense of safety and predictability, enable emotional expression, address health risks, and foster social integration.4 The staff are local community volunteers, including teachers and youth workers, who are trained and supported by specialists in child protection. Previously, child-centred spaces have been started by the Christian Children’s Fund in conflict and postconflict situations in Afghanistan, Angola, Sierra Leone, Kosovo, and East Timor, where the scale and nature of the devastation have affected children.5 Activities in the children’s centres aim to help to restore young children’s sense of safety by providing a safe place where they can play surrounded by caring adults whom they trust. The centres try to restore children’s sense of normalcy and predictability through structured activities such as singing and dancing, www.thelancet.com Vol 366 December 17/24/31, 2005