The prevalence and clinical relevance of 2R/2R TYMS genotype in patients with gastrointestinal malignancies treated with fluoropyrimidine-based chemotherapy regimens.

INTRODUCTION: The prevalence of 2R/2R TYMS genotype is variable but estimated to be around 20-30% in Caucasians. The clinical relevance of TYMS 2R/2R genotype in predicting severe fluoropyrimidine-related adverse events (FrAE) is controversial. Here, we explored the prevalence and clinical relevance of 2R/2R TYMS genotype. METHODS: Between 2011 and 2018, 126 patients were genotyped for TYMS. FrAEs were graded according to CTCAE version 5.0. Fisher's exact test was used for statistical analysis. RESULTS: The prevalence of TYMS 2R/2R genotype was 24.6%. Among patients with TYMS genotypes (N = 71) that predict decreased TS expression, 2R/2R TYMS genotype was the most common TYMS genotype seen in female (57%) and African American (60%) patients. Among patients with genotypes that predict increased TS expression (N = 55), 12 patients had grade 3-4 FrAEs (22%), while among patients with genotypes that predict decreased TS expression (N = 71), 30 patients had grade 3-4 FrAEs (42%) (p = 0.0219). Compared to patients with genotypes predicting increased TS expression, 17 out of 31 patients (55%) with TYMS 2R/2R genotype had grade 3-4 FrAEs (p = 0.0039) and 15 out 40 patients (38%) with TYMS 2R/3RC and TYMS 3RC/3RC genotype had grade 3-4 FrAEs (p = 0.1108). CONCLUSION: The prevalence of TYMS 2R/2R genotype was 24.6%, and it had a unique sex and ethnic distribution. Polymorphism in the promoter region of TYMS gene that predicts decreased TS expression due to 2R/2R variant was associated with grade 3-4 FrAEs. These data suggest that genotyping patients who are not DPD deficient for TYMS might identify patients at risk of severe FrAEs.

Spectral and spatial shifts of post-ictal slow waves in temporal lobe seizures.

Temporal lobe seizures have a significant chance to induce impairment of normal brain functions. Even after the termination of ictal discharges, during the post-ictal period, loss of consciousness, decreased responsiveness or other cognitive dysfunctions can persist. Previous studies have found various anatomical and functional abnormalities accompanying temporal lobe seizures, including an abnormal elevation of cortical slow waves. Intracranial electroencephalography studies have shown a prominent increase of lower frequency components during and following seizures that impair (complex partial seizures) but not those that preserve (simple partial seizures) normal consciousness and responsiveness. However, due to the limited spatial coverage of intracranial electroencephalography, the investigation of cortical slow waves cannot be easily extended to the whole brain. In this study, we used scalp electroencephalography to study the spectral features and spatial distribution of post-ictal slow waves with comprehensive spatial coverage. We studied simple partial, complex partial and secondarily generalized seizures in 28 patients with temporal lobe seizures. We used dense-array electroencephalography and source imaging to reconstruct the post-ictal slow-wave distribution. In the studied cohort, we found that a 'global' spectral power shift to lower frequencies accompanied the increased severity of seizures. The delta spectral power relative to higher frequency bands was highest for secondarily generalized seizures, followed by complex partial seizures and lastly simple partial seizures. In addition to this 'global' spectral shift, we found a 'regional' spatial shift in slow-wave activity. Secondarily generalized seizures and complex partial seizures exhibited increased slow waves distributed to frontal areas with spread to contralateral temporal and parietal regions than in simple partial seizures. These results revealed that a widespread cortical network including temporal and fronto-parietal cortex is involved in abnormal slow-wave activity following temporal lobe seizures. The differential spectral and spatial shifts of post-ictal electroencephalography activity in simple partial, complex partial and secondarily generalized seizures suggest a possible connection between cortical slow waves and behavioural and cognitive changes in a human epilepsy model.

The adherence to the American Association for the Study of Liver Diseases 2018 guidelines in the management of hepatocellular carcinoma and its impact on survival.

Introduction: In two Korean and Italian studies, the adherence rate (AR) to ASSLD 2005 guidelines in the management of hepatocellular carcinoma (HCC) was 60%. In a US study, the AR to American Association for the Study of Liver Disease (AASLD) 2005 guidelines was 73.3%, 26.8%, 25.3%, and 58.8% for patients with Barcelona Clinic Liver Cancer (BCLC) Stage A, B, C, and D, respectively, and nonadherence to guidelines was associated with longer overall survival (OS) in patients with BCLC Stage D. Here, we explored the AR to AASLD 2018 guidelines and its impact on OS. Methods: Between 2017 and 2019, 148 unique treatment-naïve patients with HCC were identified. Patients were staged according to the BCLC staging system and their AR to AASLD 2018 guidelines was noted. OS was estimated using Kaplan-Meier method. Survivals among patients from different groups was compared using Log-rank test. Results: The overall AR to AASLD 2018 guidelines was 83%. The AR for BCLC Stages 0, A, B, C, and D were 100%, 97%, 77%, 77%, and 38%, respectively. In patients with BCLC Stage D, the OS of patients treated with modalities adherent versus nonadherent to AASLD 2018 guidelines was 0.03 vs. 5.2 months (P = 0.0005). Otherwise, adherence versus nonadherence to AASLD 2018 guidelines showed no statistically significant differences in OS for patients with BCLC Stages 0, A, B, and C. Conclusion: The overall AR to AASLD 2018 guidelines was 83%. Nonadherence to AASLD 2018 guidelines in patients with BCLC Stage D translated into better OS.

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 (rSO(2)) sensors. Minimum rSO(2) 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 rSO(2) 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) %rSO(2) values than the minimum preictal value. Patients with at least one seizure with a %rSO(2) 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.

An evaluation of teaching physical examination to pharmacists.

BACKGROUND: Evolving scope of practice has led pharmacists to develop new skills traditionally performed by other members of the health care team, including physical examination (PE). A session to teach PE skills to pharmacists was created as part of a professional development program. The purpose of this study was to evaluate participants' perception of, barriers to and confidence in performing PE before and after the session. METHODS: A 2-hour session introduced participants to PE as part of a primary care professional development program. Surveys were administered before and after the session, and then 4 weeks later. Participants' confidence in performing PE was assessed using a 4-point unipolar scale questionnaire, and mean weighted responses were compared between the pre- and post-session surveys. RESULTS: Thirty-four pharmacists participated in the study. At baseline, 82.4% had never received formal PE education, but 38.2% performed PE in practice, including blood pressure measurement. Eighty-two percent of participants identified barriers to performing PE, the most common being lack of formal training. Participants' confidence with PE significantly increased between the pre- and post-session surveys, except for comfort with making drug therapy interventions based on PE findings. Forty-three percent of participants completed the 4-week follow-up survey, which demonstrated that the use of PE in practice remained unchanged. CONCLUSION: Prior to the session, most participants did not use PE in their practice, primarily due to a lack of formal training. The session significantly improved participants' confidence in PE, but this did not translate into short-term practice change.

Contribution of Ictal Source Imaging for Localizing Seizure Onset Zone in Patients With Focal Epilepsy.

OBJECTIVE: To determine whether seizure onset zone (SOZ) can be localized accurately prior to surgical planning in patients with focal epilepsy, we performed noninvasive EEG recordings and source localization analyses on 39 patients. METHODS: In 39 patients with focal epilepsy, we recorded and extracted 138 seizures and 1,325 interictal epileptic discharges using high-density EEG. We investigated a novel approach for directly imaging sources of seizures and interictal spikes from high-density EEG recordings, and rigorously validated it for noninvasive localization of SOZ determined from intracranial EEG findings and surgical resection volume. Conventional source imaging analyses were also performed for comparison. RESULTS: Ictal source imaging showed a concordance rate of 95% when compared to intracranial EEG or resection results. The average distance from estimation to seizure onset (intracranial) electrodes is 1.35 cm in patients with concordant results, and 0.74 cm to surgical resection boundary in patients with successful surgery. About 41% of the patients were found to have multiple types of interictal activities; coincidentally, a lower concordance rate and a significantly worse performance in localizing SOZ were observed in these patients. CONCLUSION: Noninvasive ictal source imaging with high-density EEG recording can provide highly concordant results with clinical decisions obtained by invasive monitoring or confirmed by resective surgery. By means of direct seizure imaging using high-density scalp EEG recordings, the added value of ictal source imaging is particularly high in patients with complex interictal activity patterns, who may represent the most challenging cases with poor prognosis.

A randomized controlled trial of online acceptance and commitment therapy to improve diet and physical activity among adults who are overweight/obese.

Acceptance and commitment therapy (ACT) has shown benefit for improving diet, physical activity, and weight among adults who are overweight and obese. However, research to-date in this area has primarily evaluated ACT delivered through in-person interventions, which has more limited access relative to online formats. The present study evaluated an online guided self-help program that integrated ACT with nutrition education to improve healthy eating and physical activity. A sample of 79 adults who were overweight/obese was randomized to receive the 8-week ACT on Health program plus weekly phone coaching or to a waitlist. Participants completed 5.5 ACT sessions on average (out of 8) and reported moderately high program satisfaction. Participants in the ACT condition improved significantly more than the waitlist at posttreatment on the primary outcome of healthy eating index (HEI; based on 24-hr recall assessments) and almost all secondary outcomes assessing self-reported eating behaviors, weight, mental health, weight self-stigma, and psychological inflexibility. However, no intervention effects were found for self-reported physical activity. At 8-week follow-up, improvements were maintained for most outcomes in the ACT condition, but not for the HEI. Improvements in psychological inflexibility mediated treatment effects on some outcomes, but not HEI or weight. Overall, delivering ACT through online guided self-help combined with nutrition education appears promising for improving healthy eating, weight, and self-stigma, but results for physical activity and long-term behavior change are unclear, possibly due to limitations in the ACT on Health program.

Pickleball for Inactive Mid-Life and Older Adults in Rural Utah: A Feasibility Study.

Many diseases, disabilities, and mental health conditions associated with aging can be delayed or prevented through regular exercise. Several barriers to exercise, many of which are exacerbated in rural communities, prevent mid-life and older adults from accessing its benefits. However, recently, a racquet sport named pickleball has become popular among older adults, and it appears to overcome some of these barriers. We conducted a feasibility study to evaluate the impact of a six-week pickleball intervention on measures of muscle function, cognitive function, perceived pain, and cardio-metabolic risk, as well as several psychosocial factors contributing to adherence in sedentary rural participants. Participants improved their vertical jump, cognitive performance, and reported a decrease in self-reported pain, suggesting improved physical and cognitive health across the sample. Participants also reported high levels of satisfaction and demonstrated good adherence over the duration of the study. Perhaps of greatest value was the overwhelmingly positive response from participants to the intervention and follow-up interviews reporting a desire to continue pickleball play beyond the study period. Overall, pickleball appears to be a promising intervention to, (1) elicit functional- and cognitive-related improvements, and (2) motivate mid-life and older adults to adhere to exercise sufficiently long to benefit their health.

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.

Initial refugee health assessments. New recommendations for Minnesota.

Historically, the purpose of medical screening of new refugees has been to identify acute conditions such as infections that can be effectively addressed with short-term therapy. More recently, screening of refugees who are new to Minnesota has included identifying conditions that require ongoing care. But regular screening for chronic conditions only makes sense when follow-up care can be provided. To address this issue, the Minnesota Department of Health's Refugee Health Program, in conjunction with outside experts, reviewed its guidelines for medical screening of new refugees and revised its recommendations. In addition to recommending screening for infections and other acute conditions, the new guidelines call for screening for chronic conditions and repeat testing for diseases or conditions of long latency. The guidelines take into account the ability of the screening clinic to provide ongoing care or assure the patient's transition to primary care.

Epidermal growth factor receptor-activating mutation(E746_T751>VP) in pancreatic ductal adenocarcinoma responds to erlotinib, followed by epidermal growth factor receptor resistance-mediating mutation (A647T): A case report and literature review.

Despite recent advances in treatment with multidrug chemotherapy regimens, outcomes of patients with advanced pancreatic ductal adenocarcinoma (PDAC) remain very poor. Treatment with targeted therapies has shown marginal benefits due to intrinsic or acquired resistance. Actionable mutations, while detected infrequently in patients with PDAC, are becoming increasingly used in personalized medicine. Here, we describe an epidermal growth factor receptor (EGFR)-activating mutation (E746_T751>VP) to erlotinib, a first-generation tyrosine kinase inhibitor (TKI), in a patient with metastatic PDAC. After an initial partial response to erlotinib for 12 months, the patient's disease progressed with emergence of the EGFR A647T mutation. Certainly, the patient also progressed after switching therapy to a third-generation EGFR TKI (osimertinib). This case illustrates the posttreatment evolution of EGFR A647T-mediated resistance to the first- and third-generation TKIs. To our knowledge, this is the first case to report the aforementioned activating and resistance-mediated mutations. In summary, genomic analysis performed in this patient with PDAC on the tumor biopsy and peripheral blood provided tools to understand mechanisms of response and resistance to targeted therapy with EFGR TKIs.

The Prevalence of DPYD*9A(c.85T>C) Genotype and the Genotype-Phenotype Correlation in Patients with Gastrointestinal Malignancies Treated With Fluoropyrimidines: Updated Analysis.

INTRODUCTION: The dihydropyrimidine dehydrogenase gene (DPYD)*9A (c.85T>C) genotype is relatively common. The correlation between DPYD*9A genotype and dihydropyrimidine dehydrogenase (DPD) deficiency phenotype is controversial. In a cohort of 28 patients, DPYD*9A was the most commonly diagnosed variant (13 patients [46%]) and there was a noticeable genotype-phenotype correlation. In this study we genotyped a larger cohort of a mixed racial background to explore the prevalence of DPYD*9A variant and to confirm the genotype-phenotype correlation. PATIENTS AND METHODS: Between 2011 and 2018, in addition to genotyping for high-risk DPYD variants (DPYD*2A, DPYD*13 and DPYD*9B), genotyping for DPYD*9A variant was performed on 113 patients with gastrointestinal malignancies treated with fluoropyrimidines. Fluoropyrimidines-associated toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0). Fisher exact test was used for statistical analysis. RESULTS: Heterozygous and homozygous DPYD*9A genotypes were identified in 46 (41%) and 11 (10%) patients, respectively. Among patients with DPYD*9A genotypes (n = 57), men and women represented 30 (53%) and 27 (47%) patients, respectively. Caucasian, African American, and other ethnicities represented 29 (50.9%), 26 (45.6%), and 2 (3.5%) patients, respectively. Grade 3/4 toxicities were experienced in 26 patients with DPYD*9A genotype (3 patients had homozygous status) and in 20 patients with wild type DPYD*9A (P = .4405). In patients who received full-dose fluoropyrimidines (n = 85), Grade 3/4 toxicities were experienced in 22 patients with DPYD*9A genotype (2 patients had homozygous status), and in 17 patients with wild type DPYD (P = .8275). CONCLUSION: In our updated analysis, the prevalence of heterozygous and homozygous DPYD*9A genotypes were 41% and 10%, respectively. The correlation between DPYD*9A genotype and DPD clinical phenotype was not reproduced. The noticeable correlation that we previously reported is likely because of small sample size and selection bias.

Exosomal markers (CD63 and CD9) expression and their prognostic significance using immunohistochemistry in patients with pancreatic ductal adenocarcinoma.

BACKGROUND: Exosomes are important mediators of intercellular communications and play pivotal roles in cancer progression, metastasis and chemoresistance. CD63 and CD9 are widely accepted exosomal markers. In patients with pancreatic ductal adenocarcinoma (PDAC), positive correlation between CD9 expression and overall survival (OS) was reported. CD63 expression was conserved in all patients with no reported prognostic significance. This study explored the prognostic significance of CD63 and CD9 expression using immunohistochemistry (IHC) in patients with PDAC of mixed racial background. METHODS: Between 2012 and 2016, 49 patients with PDAC had available tissues for CD63 and CD9 staining using IHC. Two pathologists independently scored the CD63 and CD9 expression. Staining intensity was graded from 1-3 and staining percentage was estimated in 10% increments. Mean Quick-score (Q-score) (Intensity X Percentage of staining) was calculated. RESULTS: The mean Q-score for CD63 and CD9 are higher in primary tumor from the pancreas compared to pancreatic tumor from metastatic sites (185 vs. 102, P=0.0002) and (48 vs. 20, P=0.0418) respectively. We fitted Cox proportion hazard regression models to investigate the impact of the covariates CD63 and CD9 on progression free survival (PFS) and OS. CD63 has significant impact on PFS (P=0.0135) and OS (P=0.003). The higher the CD63 Q-score, the longer the PFS and OS. CD9 doesn't have significant impact on PFS (P=0.5734) or OS (P=0.2682). The mean CD63 and CD9 Q-scores are slightly higher in African American (AA) compared to Caucasians (157 vs. 149, P=0.76) and (45 vs. 29, P=0.43) respectively. CONCLUSIONS: CD63 and CD9 expression is higher in primary tumor from the pancreas compared to pancreatic tumor from metastatic sites. There is correlation between CD63 expression (but not CD9 in this cohort) and PFS and OS. To our knowledge, this is the first study to show prognostic significance of CD63 expression in patients with PDAC using IHC. A trend of higher expression of CD63 and CD9 among AA compared to Caucasians was also noticed.

Germline pharmacogenomics of DPYD*9A (c.85T>C) variant in patients with gastrointestinal malignancies treated with fluoropyrimidines.

BACKGROUND: The correlation between DPYD*9A (c.85T>C) genotype and dihydropyrimidine dehydrogenase (DPD) deficiency clinical phenotype is controversial. Reference laboratories either did not perform DPYD*9A genotyping or have stopped DPYD*9A genotyping and limited genotyping to high-risk variants (DPYD*2A, DPYD*13 and DPYD*9B) only. This study explored DPYD*9A genotype and clinical phenotype correlation in patients with gastrointestinal (GI) malignancies treated with fluoropyrimidines. METHODS: Between 2011 and 2017, 67 patients with GI malignancies were genotyped for DPYD variants. Fluoropyrimidines-associated toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 3.0). Fisher's exact test was used for statistical analysis. RESULTS: DPYD variants were identified in 17 out of 67 (25%) patients. One patient was homozygous for DPYD*9A variant and one patient was double heterozygous for DPYD*9A and DPYD*9B variants. In patients with identified DPYD variants, 13/17 (76%) patients had DPYD*9A variant, 3/17 (18%) patients had DPYD*2A variant and 2/17 (12%) patient had DPYD*9B variant. Only patients genotyped prior to 2015 were genotyped for DPYD*9A variant (N=28). Of those, 13/28 patients (46%) had DPYD*9A variant. Grade 3-4 diarrhea was associated with DPYD*9A variant in patients treated with full dose fluoropyrimidines (P=0.0055). CONCLUSIONS: In our cohort, DPYD*9A variant was the most common diagnosed variant. The correlation between DPYD*9A genotype and DPD deficiency in clinical phenotype was noticeable in patients who received full dose fluoropyrimidines as they all experienced grade 3-4 toxicities (diarrhea).

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.

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.

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.

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.

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.