Cindy Nelson

Dynamic imaging of seizure activity in pediatric epilepsy patients

OBJECTIVE To investigate the feasibility of using noninvasive EEG source imaging approach to image continuous seizure activity in pediatric epilepsy patients. METHODS Nine pediatric patients with medically intractable epilepsy were included in this study. Eight of the patients had extratemporal lobe epilepsy and one had temporal lobe epilepsy. All of the patients underwent resective surgery and seven of them underwent intracranial EEG (iEEG) monitoring. The ictal EEG was analyzed using a noninvasive dynamic seizure imaging (DSI) approach. The DSI approach separates scalp EEGs into independent components and extracts the spatio-temporal ictal features to achieve dynamic imaging of seizure sources. Surgical resection and intracranial recordings were used to validate the noninvasive imaging results. RESULTS The DSI determined seizure onset zones (SOZs) in these patients were localized within or in close vicinity to the surgically resected region. In the seven patients with intracranial monitoring, the estimated seizure onset sources were concordant with the seizure onset zones of iEEG. The DSI also localized the multiple foci involved in the later seizure propagation, which were confirmed by the iEEG recordings. CONCLUSIONS Dynamic seizure imaging can noninvasively image the seizure activations in pediatric patients with both temporal and extratemporal lobe epilepsy. SIGNIFICANCE EEG seizure imaging can potentially be used to noninvasively image the SOZs and aid the pre-surgical planning in pediatric epilepsy patients.

Characteristics of postictal generalized EEG suppression in children

Although the pathophysiologic mechanism of sudden unexpected death in epilepsy (SUDEP) is unknown, autonomic dysfunction is thought to be the most likely. It has been hypothesized that respiratory depression resulting in SUDEP may be secondary to postictal generalized electroencephalography suppression (PGES). We sought to determine the characteristics of PGES in children. This included whether PGES was associated with ictally mediated autonomic changes and potential increased risk of SUDEP. Children admitted to our Pediatric Epilepsy Monitoring Unit between 3/2009 and 10/2011 were prospectively recruited. Clinical and electrophysiological data from children with PGES were compared to those without PGES. Data included the occurrence of peri-ictal tachycardia, bradycardia, and hypoxemia. Potential SUDEP risk was assessed using SUDEP-7 Inventory scores. Thirty seven children with 168 seizures were analyzed. PGES was observed following 27/168 (16.1%) seizures in 12/37 (32.4%) children. Only primary and secondarily generalized tonic clonic seizures were marked by PGES. PGES was significantly associated with peri-ictal tachycardia (p=0.019) and hypoxemia (p=0.005). Children with PGES had significantly higher SUDEP-7 Inventory scores than those without PGES (4.2 ± 1.3 versus 2.8 ± 1.4, p=0.007). SUDEP-7 scores were not significantly different between children with and without peri-ictal tachycardia (3.4 ± 1.3 versus 2.5±1.6, p=0.12), bradycardia (4 ± 2 versus 2.9 ± 1.4, p=0.45), or hypoxemia (3.4 ± 1.5 versus 2.4 ± 1.3, p=0.051). Based on our data, PGES is not rare in children. Children with PGES may be at greater risk for SUDEP as measured by the SUDEP-7 Inventory.

Noninvasive Imaging of the High Frequency Brain Activity in Focal Epilepsy Patients

High-frequency (HF) activity represents a potential biomarker of the epileptogenic zone in epilepsy patients, the removal of which is considered to be crucial for seizure-free surgical outcome. We proposed a high frequency source imaging (HFSI) approach to noninvasively image the brain sources of the scalp-recorded HF EEG activity. Both computer simulation and clinical patient data analysis were performed to investigate the feasibility of using the HFSI approach to image the sources of HF activity from noninvasive scalp EEG recordings. The HF activity was identified from high-density scalp recordings after high-pass filtering the EEG data and the EEG segments with HF activity were concatenated together to form repetitive HF activity. Independent component analysis was utilized to extract the components corresponding to the HF activity. Noninvasive EEG source imaging using realistic geometric boundary element head modeling was then applied to image the sources of the pathological HF brain activity. Five medically intractable focal epilepsy patients were studied and the estimated sources were found to be concordant with the surgical resection or intracranial recordings of the patients. The present study demonstrates, for the first time, that source imaging from the scalp HF activity could help to localize the seizure onset zone and provide a novel noninvasive way of studying the epileptic brain in humans. This study also indicates the potential application of studying HF activity in the presurgical planning of medically intractable epilepsy patients.

Periictal cerebral tissue hypoxemia: A potential marker of SUDEP risk

Cerebral oximetry has not been explored in patients experiencing seizures in the epilepsy monitoring unit (EMU). The purpose of our study was to evaluate the feasibility of periictal measurement of cerebral oxygenation using noninvasive cerebral tissue oximetry and to determine whether there was evidence of cerebral hypoxemia during generalized seizures. Cerebral oxygen saturation findings were subsequently correlated with sudden unexpected death in epilepsy (SUDEP) risk factors. We prospectively evaluated six patients admitted to our EMU with histories of generalized tonic–clonic seizures (GTCS) with prolonged scalp electroencephalography (EEG) and two regional cerebral oxygen saturation (rSO2) sensors. Minimum rSO2 values were recorded in the 5 min preceding seizure onset, during the seizure, and in the 5 min following seizure offset. SUDEP risk was assessed using the SUDEP‐7 Inventory. Cerebral oximetry was well tolerated, with a mean duration of rSO2 monitoring of 81.1 h. Cerebral oxygen saturation data were available from at least one sensor in 9 (90%) of 10 seizures; only 6 (60%) of 10 seizures had useable periictal digital pulse oximetry data. GTCS were associated with significantly lower minimum ictal (p = 0.003) and postictal (p = 0.004) %rSO2 values than the minimum preictal value. Patients with at least one seizure with a %rSO2 decrease of ≥20% tended to have higher SUDEP‐7 Inventory scores (mean SUDEP‐7 Inventory score 7 ± 2.8) versus patients without recorded desaturations (4.3 ± 0.5, p = 0.08). Larger studies are needed to determine the value of cerebral oximetry in the identification of patients at risk of SUDEP.

Questioning the role of abuse in behavioral spells and epilepsy

Past sexual trauma is frequently linked to the development of behavioral spells, present among 30% of patients admitted for video/EEG monitoring. Current attempts to verify and explore mechanisms in this reported association revealed that patients with epilepsy (n=58) and those with behavioral spells (n=38) did not differ in their self-report of past sexual trauma (among approximately 38% in each group). Ninety percent (90%) of men with behavioral spells endorsed past physical abuse, however, compared with 45% of men with epilepsy, and 40% of men with spells likely met current criteria for posttraumatic stress disorder. Among all patients, the presence of past physical, but not sexual, abuse positively predicted the diagnosis of spells rather than epilepsy. Current findings do not support a preponderance of sexual trauma in behavioral spells, yet within the subset of men with spells, greater exposure to physical abuse and current symptoms of posttraumatic stress disorder may be important etiological and sustaining factors.

High density scalp EEG in frontal lobe epilepsy

PURPOSE Localization of seizures in frontal lobe epilepsy using the 10-20 system scalp EEG is often challenging because neocortical seizure can spread rapidly, significant muscle artifact, and the suboptimal spatial resolution for seizure generators involving mesial frontal lobe cortex. Our aim in this study was to determine the value of visual interpretation of 76 channel high density EEG (hdEEG) monitoring (10-10 system) in patients with suspected frontal lobe epilepsy, and to evaluate concordance with MRI, subtraction ictal SPECT co-registered to MRI (SISCOM), conventional EEG, and intracranial EEG (iEEG). METHODS We performed a retrospective cohort study of 14 consecutive patients who underwent hdEEG monitoring for suspected frontal lobe seizures. The gold standard for localization was considered to be iEEG. Concordance of hdEEG findings with MRI, subtraction ictal SPECT co-registered to MRI (SISCOM), conventional 10-20 EEG, and iEEG as well as correlation of hdEEG localization with surgical outcome were examined. RESULTS hdEEG localization was concordant with iEEG in 12/14 and was superior to conventional EEG 3/14 (p<0.01) and SISCOM 3/12 (p<0.01). hdEEG correctly lateralized seizure onset in 14/14 cases, compared to 9/14 (p=0.04) cases with conventional EEG. Seven patients underwent surgical resection, of whom five were seizure free. CONCLUSIONS hdEEG monitoring should be considered in patients with suspected frontal epilepsy requiring localization of epileptogenic brain. hdEEG may assist in developing a hypothesis for iEEG monitoring and could potentially augment EEG source localization.

Dynamic seizure imaging in patients with extratemporal lobe epilepsy

Epilepsy is a common neurological disease that affects about 50 million people worldwide. Extratemporal lobe epilepsy, which represents an important type of epilepsy, may involve seizure activity in various lobes and the surgical treatment in these patients tends to have less favorable surgical outcome. Noninvasive seizure imaging in drug-resistant patients is of vital importance to image the seizure onset zones (SOZs) and understand the mechanisms for an improved treatment plan. In this study, we directly imaged the seizure sources in 8 extratemporal lobe partial epilepsy patients from noninvasive EEG. The surgically resected regions and SOZs identified from intracranial EEG (iEEG) recordings were used to evaluate the source imaging results. All of the eight patients underwent resective surgery and the estimated seizure sources were co-located with the resection zone. Seven of the patients had iEEG recordings available and the source imaging results were concordant with the SOZs marked on the intracranial recording grid. The present results suggest that dynamic seizure imaging could be potentially useful to image the SOZs of extratemporal lobe seizures and help the pre-surgical planning of epilepsy patients.

Erratum: Noninvasive imaging of the high frequency brain activity in focal epilepsy patients (IEEE Transactions on Biomedical Engineering (2014) 61:6(1660-1667))

Physical units in Figs 3-5 in the above-named work [ibid., vol. 61, no. 6, pp. 1660–1667, Jun. 2014] were found mistyped. The corrected figures are provided here.