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1.
Epilepsy Behav ; 127: 108510, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34991054

ABSTRACT

During the COVID-19 pandemic, restrictions on reimbursement for telehealth visits were lifted and this visit type was suddenly available to patients around the United States of America. Telehealth visits offer potential cost savings for patients and families, which may vary by region of the world studied. Also, aggressiveness of the care patients receive may differ, and patients or families may be more likely to choose one visit type over another based on seizure control. This is a prospective face-to-face clinic versus telehealth clinic visit comparison study involving patients with seizures, their legal guardians, and caretakers who attend clinic. We compared travel distance, work-related factors, childcare, satisfaction of care, changes in seizure medication or diagnostics tests ordered, and willingness to cancel appointments to better understand the behavioral patterns of patients, caretakers, and providers. Our results indicate that many patients and families still prefer in-person interactions with their medical providers. Patient and family satisfaction levels were equal with both visit types. No significant difference was seen in medical management between face-to-face and telehealth visits. Also, prior seizure control did not dictate the type of visit chosen. Telehealth participants were significantly more willing to cancel appointments if asked to switch to face-to-face then face-to-face participants asked to complete telehealth visits. Surprisingly, we found that patients and families choosing telehealth were not statistically more likely to be employed or take less time off work. Also, distance from home to office was not significantly shorter for participants choosing face-to-face visits. Offering a combination of telehealth and face-to-face visits appears to be the optimal strategy in caring for patients with controlled and uncontrolled seizure disorders to ensure adherence with clinic visits and satisfaction with care. Our study suggests that providers are equally willing to adjust medications or order additional diagnostic testing regardless of visit type. Patients and families may be less likely to cancel telehealth visits than face-to-face visits; this finding may translate to improved seizure control and long-term decreased cost of care.


Subject(s)
COVID-19 , Epilepsy , Telemedicine , Ambulatory Care , Epilepsy/epidemiology , Epilepsy/therapy , Humans , Pandemics , Prospective Studies , SARS-CoV-2 , United States
2.
N Engl J Med ; 379(24): 2342-2350, 2018 12 13.
Article in English | MEDLINE | ID: mdl-30280658

ABSTRACT

BACKGROUND: An earlier analysis in this phase 3 trial showed that durvalumab significantly prolonged progression-free survival, as compared with placebo, among patients with stage III, unresectable non-small-cell lung cancer (NSCLC) who did not have disease progression after concurrent chemoradiotherapy. Here we report the results for the second primary end point of overall survival. METHODS: We randomly assigned patients, in a 2:1 ratio, to receive durvalumab intravenously, at a dose of 10 mg per kilogram of body weight, or matching placebo every 2 weeks for up to 12 months. Randomization occurred 1 to 42 days after the patients had received chemoradiotherapy and was stratified according to age, sex, and smoking history. The primary end points were progression-free survival (as assessed by blinded independent central review) and overall survival. Secondary end points included the time to death or distant metastasis, the time to second progression, and safety. RESULTS: Of the 713 patients who underwent randomization, 709 received the assigned intervention (473 patients received durvalumab and 236 received placebo). As of March 22, 2018, the median follow-up was 25.2 months. The 24-month overall survival rate was 66.3% (95% confidence interval [CI], 61.7 to 70.4) in the durvalumab group, as compared with 55.6% (95% CI, 48.9 to 61.8) in the placebo group (two-sided P=0.005). Durvalumab significantly prolonged overall survival, as compared with placebo (stratified hazard ratio for death, 0.68; 99.73% CI, 0.47 to 0.997; P=0.0025). Updated analyses regarding progression-free survival were similar to those previously reported, with a median duration of 17.2 months in the durvalumab group and 5.6 months in the placebo group (stratified hazard ratio for disease progression or death, 0.51; 95% CI, 0.41 to 0.63). The median time to death or distant metastasis was 28.3 months in the durvalumab group and 16.2 months in the placebo group (stratified hazard ratio, 0.53; 95% CI, 0.41 to 0.68). A total of 30.5% of the patients in the durvalumab group and 26.1% of those in the placebo group had grade 3 or 4 adverse events of any cause; 15.4% and 9.8% of the patients, respectively, discontinued the trial regimen because of adverse events. CONCLUSIONS: Durvalumab therapy resulted in significantly longer overall survival than placebo. No new safety signals were identified. (Funded by AstraZeneca; PACIFIC ClinicalTrials.gov number, NCT02125461 .).


Subject(s)
Antibodies, Monoclonal/administration & dosage , Antineoplastic Agents, Immunological/administration & dosage , Carcinoma, Non-Small-Cell Lung/drug therapy , Chemoradiotherapy , Lung Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal/adverse effects , Antineoplastic Agents, Immunological/adverse effects , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/radiotherapy , Female , Humans , Infusions, Intravenous , Intention to Treat Analysis , Kaplan-Meier Estimate , Lung Neoplasms/mortality , Lung Neoplasms/radiotherapy , Male , Middle Aged , Survival Rate
3.
N Engl J Med ; 377(20): 1919-1929, 2017 11 16.
Article in English | MEDLINE | ID: mdl-28885881

ABSTRACT

BACKGROUND: Most patients with locally advanced, unresectable, non-small-cell lung cancer (NSCLC) have disease progression despite definitive chemoradiotherapy (chemotherapy plus concurrent radiation therapy). This phase 3 study compared the anti-programmed death ligand 1 antibody durvalumab as consolidation therapy with placebo in patients with stage III NSCLC who did not have disease progression after two or more cycles of platinum-based chemoradiotherapy. METHODS: We randomly assigned patients, in a 2:1 ratio, to receive durvalumab (at a dose of 10 mg per kilogram of body weight intravenously) or placebo every 2 weeks for up to 12 months. The study drug was administered 1 to 42 days after the patients had received chemoradiotherapy. The coprimary end points were progression-free survival (as assessed by means of blinded independent central review) and overall survival (unplanned for the interim analysis). Secondary end points included 12-month and 18-month progression-free survival rates, the objective response rate, the duration of response, the time to death or distant metastasis, and safety. RESULTS: Of 713 patients who underwent randomization, 709 received consolidation therapy (473 received durvalumab and 236 received placebo). The median progression-free survival from randomization was 16.8 months (95% confidence interval [CI], 13.0 to 18.1) with durvalumab versus 5.6 months (95% CI, 4.6 to 7.8) with placebo (stratified hazard ratio for disease progression or death, 0.52; 95% CI, 0.42 to 0.65; P<0.001); the 12-month progression-free survival rate was 55.9% versus 35.3%, and the 18-month progression-free survival rate was 44.2% versus 27.0%. The response rate was higher with durvalumab than with placebo (28.4% vs. 16.0%; P<0.001), and the median duration of response was longer (72.8% vs. 46.8% of the patients had an ongoing response at 18 months). The median time to death or distant metastasis was longer with durvalumab than with placebo (23.2 months vs. 14.6 months; P<0.001). Grade 3 or 4 adverse events occurred in 29.9% of the patients who received durvalumab and 26.1% of those who received placebo; the most common adverse event of grade 3 or 4 was pneumonia (4.4% and 3.8%, respectively). A total of 15.4% of patients in the durvalumab group and 9.8% of those in the placebo group discontinued the study drug because of adverse events. CONCLUSIONS: Progression-free survival was significantly longer with durvalumab than with placebo. The secondary end points also favored durvalumab, and safety was similar between the groups. (Funded by AstraZeneca; PACIFIC ClinicalTrials.gov number, NCT02125461 .).


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents/therapeutic use , B7-H1 Antigen/antagonists & inhibitors , Carcinoma, Non-Small-Cell Lung/therapy , Lung Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal/adverse effects , Antineoplastic Agents/adverse effects , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/secondary , Chemoradiotherapy , Disease-Free Survival , Female , Humans , Intention to Treat Analysis , Kaplan-Meier Estimate , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging
4.
J Obstet Gynaecol Res ; 44(9): 1779-1786, 2018 Sep.
Article in English | MEDLINE | ID: mdl-29974633

ABSTRACT

AIM: To compare the efficacy between dienogest and levonorgestrel-releasing intrauterine system (LNG-IUS) after laparoscopic surgery for endometriosis. METHODS: A total of 285 women were diagnosed as endometriosis by laparoscopy between 2011 and 2015. Patients were grouped into no treatment (n = 83), treatment with dienogest (n =130) and treatment with LNG-IUS (n =72) after laparoscopic surgery. The changes of the pain scores were checked at 6, 12 and 24 months after the surgery, and the rates of disease recurrence and treatment discontinuation rate were determined. RESULTS: The participants' mean age was 38.9 years (range 21-54 years). The mean age of LNG-IUS group (43.7 years) was significantly higher than the no treatment and dienogest groups (39.3 vs 33.9 years, respectively). At 6 and 12 months, the median pain scores in treatment (dienogest and LNG-IUS) groups were significantly lower than control group. Both treatment groups had significantly lower recurrence rate than control group (3.8% and 9.7%, respectively, vs 32.5%, P =0.001). No significant difference was found in the recurrence rate between the two treatment groups (P =0.461). Patients in the LNG-IUS group showed lower rate of discontinuation due to complication (27.8%) than those in dienogest group (35.6%, P =0.010). CONCLUSION: LNG-IUS treatment in the patients with endometriosis is effective for postoperative pain control and preventing recurrence, however, the LNG-IUS group is older, it is difficult to compare the efficacy between dienogest and LNG-IUS in present study.


Subject(s)
Contraceptive Agents, Female/pharmacology , Endometriosis/therapy , Intrauterine Devices, Medicated , Levonorgestrel/pharmacology , Nandrolone/analogs & derivatives , Outcome Assessment, Health Care , Pain, Postoperative/drug therapy , Pelvic Pain/therapy , Adult , Contraceptive Agents, Female/administration & dosage , Endometriosis/drug therapy , Endometriosis/surgery , Female , Humans , Laparoscopy , Levonorgestrel/administration & dosage , Middle Aged , Nandrolone/administration & dosage , Nandrolone/pharmacology , Pelvic Pain/drug therapy , Pelvic Pain/surgery , Young Adult
5.
J Clin Oncol ; 40(12): 1301-1311, 2022 04 20.
Article in English | MEDLINE | ID: mdl-35108059

ABSTRACT

PURPOSE: The phase III PACIFIC trial compared durvalumab with placebo in patients with unresectable, stage III non-small-cell lung cancer and no disease progression after concurrent chemoradiotherapy. Consolidation durvalumab was associated with significant improvements in the primary end points of overall survival (OS; stratified hazard ratio [HR], 0.68; 95% CI, 0.53 to 0.87; P = .00251) and progression-free survival (PFS [blinded independent central review; RECIST v1.1]; stratified HR, 0.52; 95% CI, 0.42 to 0.65; P < .0001), with manageable safety. We report updated, exploratory analyses of survival, approximately 5 years after the last patient was randomly assigned. METHODS: Patients with WHO performance status 0 or 1 (any tumor programmed cell death-ligand 1 status) were randomly assigned (2:1) to durvalumab (10 mg/kg intravenously; administered once every 2 weeks for 12 months) or placebo, stratified by age, sex, and smoking history. Time-to-event end point analyses were performed using stratified log-rank tests. Medians and landmark survival rates were estimated using the Kaplan-Meier method. RESULTS: Seven hundred and nine of 713 randomly assigned patients received durvalumab (473 of 476) or placebo (236 of 237). As of January 11, 2021 (median follow-up, 34.2 months [all patients]; 61.6 months [censored patients]), updated OS (stratified HR, 0.72; 95% CI, 0.59 to 0.89; median, 47.5 v 29.1 months) and PFS (stratified HR, 0.55; 95% CI, 0.45 to 0.68; median, 16.9 v 5.6 months) remained consistent with the primary analyses. Estimated 5-year rates (95% CI) for durvalumab and placebo were 42.9% (38.2 to 47.4) versus 33.4% (27.3 to 39.6) for OS and 33.1% (28.0 to 38.2) versus 19.0% (13.6 to 25.2) for PFS. CONCLUSION: These updated analyses demonstrate robust and sustained OS and durable PFS benefit with durvalumab after chemoradiotherapy. An estimated 42.9% of patients randomly assigned to durvalumab remain alive at 5 years and 33.1% of patients randomly assigned to durvalumab remain alive and free of disease progression, establishing a new benchmark for standard of care in this setting.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Antibodies, Monoclonal/adverse effects , Carcinoma, Non-Small-Cell Lung/drug therapy , Chemoradiotherapy , Disease Progression , Humans , Lung Neoplasms/drug therapy
6.
Clin Lung Cancer ; 23(8): 720-730, 2022 12.
Article in English | MEDLINE | ID: mdl-36038416

ABSTRACT

BACKGROUND: Brigatinib is a next-generation anaplastic lymphoma kinase (ALK) inhibitor with demonstrated efficacy in locally advanced and metastatic non-small cell lung cancer (NSCLC) in crizotinib-refractory and ALK inhibitor-naive settings. This analysis assessed brigatinib in Asian vs. non-Asian patients from the first-line ALTA-1L trial. PATIENTS AND METHODS: This was a subgroup analysis from the phase III ALTA-1L trial of brigatinib vs. crizotinib in ALK inhibitor-naive ALK+ NSCLC. The primary endpoint was progression-free survival (PFS) as assessed by blinded independent review committee (BIRC). Secondary endpoints included confirmed objective response rate (ORR) and overall survival (OS) in the overall population and BIRC-assessed intracranial ORR and PFS in patients with brain metastases. RESULTS: Of the 275 randomized patients, 108 were Asian. Brigatinib showed consistent superiority in BIRC-assessed PFS vs. crizotinib in Asian (hazard ratio [HR]: 0.35 [95% CI: 0.20-0.59]; log-rank P = .0001; median 24.0 vs. 11.1 months) and non-Asian (HR: 0.56 [95% CI: 0.38-0.84]; log-rank P = .0041; median 24.7 vs. 9.4 months) patients. Results were consistent with investigator-assessed PFS and BIRC-assessed intracranial PFS. Brigatinib was well tolerated. Toxicity profiles and dose modification rates were similar between Asian and non-Asian patients. CONCLUSION: Efficacy with brigatinib was consistently better than with crizotinib in Asian and non-Asian patients with locally advanced or metastatic ALK inhibitor-naive ALK-+ NSCLC. There were no clinically notable differences in overall safety in Asian vs. non-Asian patients.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/ethnology , Crizotinib/adverse effects , Lung Neoplasms/drug therapy , Lung Neoplasms/ethnology , Lung Neoplasms/pathology , Protein Kinase Inhibitors/therapeutic use , Asian People
7.
J Thorac Oncol ; 16(5): 860-867, 2021 05.
Article in English | MEDLINE | ID: mdl-33476803

ABSTRACT

INTRODUCTION: In the Phase 3, placebo-controlled PACIFIC trial of patients with unresectable, stage III NSCLC without disease progression after concurrent chemoradiotherapy, consolidative durvalumab was associated with significant improvements in the primary end points of overall survival (OS) (hazard ratio [HR] = 0.68; 95% confidence interval [CI]: 0.53-0.87; p = 0.00251; data cutoff, March 22, 2018) and progression-free survival (PFS) (blinded independent central review; Response Evaluation Criteria in Solid Tumors version 1.1) (HR = 0.52; 95% CI: 0.42-65; p < 0.0001; February 13, 2017) with manageable safety. Here, we report updated analyses of OS and PFS, approximately 4 years after the last patient was randomized. METHODS: Patients with WHO performance status of 0 or 1 (and any tumor programmed death-ligand 1 status) were randomized (2:1) to intravenous durvalumab (10 mg/kg) or placebo, administered every 2 weeks (≤12 months), stratified by age, sex, and smoking history. OS and PFS were analyzed using a stratified log-rank test in the intent-to-treat population. Medians and 4-year OS and PFS rates were estimated by the Kaplan-Meier method. RESULTS: Overall, 709 of 713 randomized patients received durvalumab (n/N=473/476) or placebo (n/N=236/237). As of March 20, 2020 (median follow-up = 34.2 months; range: 0.2-64.9), updated OS (HR = 0.71; 95% CI: 0.57-0.88) and PFS (HR = 0.55; 95% CI: 0.44-0.67) remained consistent with the primary analyses. The median OS for durvalumab was reached (47.5 mo; placebo, 29.1 months). Estimated 4-year OS rates were 49.6% versus 36.3% for durvalumab versus placebo, and 4-year PFS rates were 35.3% versus 19.5% respectively. CONCLUSION: These updated exploratory analyses demonstrate durable PFS and sustained OS benefit with durvalumab after chemoradiotherapy. An estimated 49.6% of patients randomized to durvalumab remain alive at 4 years (placebo, 36.3%), and 35.3% remain alive and progression-free (placebo, 19.5%).


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Antibodies, Monoclonal/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Chemoradiotherapy , Humans , Lung Neoplasms/drug therapy
8.
Front Neurosci ; 14: 409, 2020.
Article in English | MEDLINE | ID: mdl-32435182

ABSTRACT

The success of surgical resection in epilepsy patients depends on preserving functionally critical brain regions, while removing pathological tissues. Being the gold standard, electro-cortical stimulation mapping (ESM) helps surgeons in localizing the function of eloquent cortex through electrical stimulation of electrodes placed directly on the cortical brain surface. Due to the potential hazards of ESM, including increased risk of provoked seizures, electrocorticography based functional mapping (ECoG-FM) was introduced as a safer alternative approach. However, ECoG-FM has a low success rate when compared to the ESM. In this study, we address this critical limitation by developing a new algorithm based on deep learning for ECoG-FM and thereby we achieve an accuracy comparable to ESM in identifying eloquent language cortex. In our experiments, with 11 epilepsy patients who underwent presurgical evaluation (through deep learning-based signal analysis on 637 electrodes), our proposed algorithm obtained an accuracy of 83.05% in identifying language regions, an exceptional 23% improvement with respect to the conventional ECoG-FM analysis (∼60%). Our findings have demonstrated, for the first time, that deep learning powered ECoG-FM can serve as a stand-alone modality and avoid likely hazards of the ESM in epilepsy surgery. Hence, reducing the potential for developing post-surgical morbidity in the language function.

9.
Paediatr Anaesth ; 19(5): 507-12, 2009 May.
Article in English | MEDLINE | ID: mdl-19453583

ABSTRACT

BACKGROUND: Magnetoencephalography (MEG) is increasingly used in the presurgical evaluation of pediatric seizure patients. Many pediatric patients require sedation or anesthesia to tolerate these exams. However, the available literature on anesthetic management in this population is very limited. METHODS: We retrospectively reviewed the records of all patients who underwent MEG scanning at our institution with regard to the interaction of anesthetic management and quality of scan data. RESULTS: High-dose propofol infusions (> or =200 microg.kg(-1).min(-1)) were associated with high frequency artifacts that interfered with the identification of epileptiform discharges. Lower-dose propofol infusions (< or =100 microg.kg(-1).min(-1)) did not produce artifacts but required co-administration of fentanyl to prevent patient motion. Dexmedetomidine infusions were not associated with signal artifacts and prevented patient motion very well in our initial patients and became our standard technique. CONCLUSION: In our experience, dexmedetomidine infusions are preferable to propofol-based techniques for pediatric MEG scans due to the absence of adverse effect on interictal activity.


Subject(s)
Anesthesia/methods , Dexmedetomidine/pharmacology , Magnetoencephalography/drug effects , Preoperative Care/methods , Propofol/pharmacology , Adolescent , Analgesics, Non-Narcotic/pharmacology , Anesthetics, Intravenous/pharmacology , Artifacts , Child , Child, Preschool , Dose-Response Relationship, Drug , Epilepsy/diagnosis , Epilepsy/surgery , Female , Fentanyl/administration & dosage , Humans , Magnetoencephalography/methods , Male , Retrospective Studies
10.
Behav Neurol ; 2015: 237436, 2015.
Article in English | MEDLINE | ID: mdl-26146459

ABSTRACT

Objective evaluation of language function is critical for children with intractable epilepsy under consideration for epilepsy surgery. The purpose of this preliminary study was to evaluate word recognition in children with intractable epilepsy by using magnetoencephalography (MEG). Ten children with intractable epilepsy (M/F 6/4, mean ± SD 13.4 ± 2.2 years) were matched on age and sex to healthy controls. Common nouns were presented simultaneously from visual and auditory sensory inputs in "match" and "mismatch" conditions. Neuromagnetic responses M1, M2, M3, M4, and M5 with latencies of ~100 ms, ~150 ms, ~250 ms, ~350 ms, and ~450 ms, respectively, elicited during the "match" condition were identified. Compared to healthy children, epilepsy patients had both significantly delayed latency of the M1 and reduced amplitudes of M3 and M5 responses. These results provide neurophysiologic evidence of altered word recognition in children with intractable epilepsy.


Subject(s)
Cerebral Cortex/pathology , Epilepsy/pathology , Language , Memory/physiology , Adolescent , Brain Mapping , Cerebral Cortex/physiopathology , Child , Epilepsy/physiopathology , Epilepsy/therapy , Female , Humans , Magnetoencephalography/methods , Male , Treatment Outcome
11.
Arch Pharm Res ; 26(4): 312-6, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12735690

ABSTRACT

The oriental herbal combination allergina has been shown to inhibit allergic inflammation. In the present study, we demonstrate that the oral administration of allergina markedly inhibits the progression of inflammatory diseases, such as graft-versus-host diseases (in the allogeneic bone marrow transplantation and the parent-into-F1 transplantation models), collagen-induced arthritis and sheep red blood cell-induced delayed type hypersensitivity. The immunosuppressive activity of allergina in vivo appears to be associated, at least in part, with the inhibition of tumor necrosis factor-alpha production. In conclusion, our results suggest that allergina could be useful as a immunosuppressive agent for the treatment of macrophage-related inflammatory disease.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Collagen Type II/administration & dosage , Inflammation/drug therapy , Inflammation/pathology , Lipopolysaccharides/adverse effects , Macrophages/pathology , Phytotherapy , Plant Extracts/therapeutic use , Tumor Necrosis Factor-alpha/biosynthesis , Tumor Necrosis Factor-alpha/drug effects , Animals , Arthritis, Experimental/drug therapy , Arthritis, Experimental/prevention & control , Graft vs Host Disease/drug therapy , Graft vs Host Disease/prevention & control , Inflammation/prevention & control , Male , Medicine, East Asian Traditional , Mice , Mice, Inbred DBA
12.
J Neurosurg Pediatr ; 14(3): 287-95, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24995815

ABSTRACT

Accurate language localization expands surgical treatment options for epilepsy patients and reduces the risk of postsurgery language deficits. Electrical cortical stimulation mapping (ESM) is considered to be the clinical gold standard for language localization. While ESM affords clinically valuable results, it can be poorly tolerated by children, requires active participation and compliance, carries a risk of inducing seizures, is highly time consuming, and is labor intensive. Given these limitations, alternative and/or complementary functional localization methods such as analysis of electrocorticographic (ECoG) activity in high gamma frequency band in real time are needed to precisely identify eloquent cortex in children. In this case report, the authors examined 1) the use of real-time functional mapping (RTFM) for language localization in a high gamma frequency band derived from ECoG to guide surgery in an epileptic pediatric patient and 2) the relationship of RTFM mapping results to postsurgical language outcomes. The authors found that RTFM demonstrated relatively high sensitivity (75%) and high specificity (90%) when compared with ESM in a "next-neighbor" analysis. While overlapping with ESM in the superior temporal region, RTFM showed a few other areas of activation related to expressive language function, areas that were eventually resected during the surgery. The authors speculate that this resection may be associated with observed postsurgical expressive language deficits. With additional validation in more subjects, this finding would suggest that surgical planning and associated assessment of the risk/benefit ratio would benefit from information provided by RTFM mapping.


Subject(s)
Brain Mapping/methods , Cerebral Cortex/physiopathology , Electric Stimulation , Electroencephalography , Epilepsies, Partial/surgery , Language , Speech , Adolescent , Anticonvulsants/therapeutic use , Epilepsies, Partial/drug therapy , Epilepsies, Partial/physiopathology , Female , Humans , Neuropsychological Tests , Sensitivity and Specificity
13.
Clin EEG Neurosci ; 45(3): 205-11, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24293161

ABSTRACT

SIGFRIED (SIGnal modeling For Real-time Identification and Event Detection) software provides real-time functional mapping (RTFM) of eloquent cortex for epilepsy patients preparing to undergo resective surgery. This study presents the first application of paradigms used in functional magnetic resonance (fMRI) and electrical cortical stimulation mapping (ESM) studies for shared functional cortical mapping in the context of RTFM. Results from the 3 modalities are compared. A left-handed 13-year-old male with intractable epilepsy participated in functional mapping for localization of eloquent language cortex with fMRI, ESM, and RTFM. For RTFM, data were acquired over the frontal and temporal cortex. Several paradigms were sequentially presented: passive (listening to stories) and active (picture naming and verb generation). For verb generation and story processing, fMRI showed atypical right lateralizing language activation within temporal lobe regions of interest and bilateral frontal activation with slight right lateralization. Left hemisphere ESM demonstrated no eloquent language areas. RTFM procedures using story processing and picture naming elicited activity in the right lateral and basal temporal regions. Verb generation elicited strong right lateral temporal lobe activation, as well as left frontal lobe activation. RTFM results confirmed atypical language lateralization evident from fMRI and ESM. We demonstrated the feasibility and usefulness of a new RTFM stimulation paradigm during presurgical evaluation. Block design paradigms used in fMRI may be optimal for this purpose. Further development is needed to create age-appropriate RTFM test batteries.


Subject(s)
Brain Mapping/methods , Brain-Computer Interfaces , Cerebral Cortex/physiopathology , Computer Simulation , Diagnosis, Computer-Assisted/methods , Electroencephalography/methods , Epilepsy/diagnosis , Epilepsy/physiopathology , Image Interpretation, Computer-Assisted/methods , Imaging, Three-Dimensional/methods , Magnetic Resonance Imaging/methods , Signal Processing, Computer-Assisted , Software , Adolescent , Cerebral Cortex/surgery , Dominance, Cerebral/physiology , Electric Stimulation/methods , Epilepsy/surgery , Feasibility Studies , Frontal Lobe/physiopathology , Humans , Male , Multimodal Imaging/methods , Speech Perception/physiology , Temporal Lobe/physiopathology , Verbal Behavior/physiology , Vocabulary
14.
Article in English | MEDLINE | ID: mdl-24111197

ABSTRACT

Planning for epilepsy surgery depends substantially on the localization of brain cortical areas responsible for sensory, motor, or cognitive functions, clinically also known as eloquent cortex. In this paper, we present the novel software package 'cortiQ' that allows clinicians to localize eloquent cortex, thus providing a safe margin for surgical resection with a low incidence of neurological deficits. This software can be easily used in addition to traditional mapping procedures such as the electrical cortical stimulation (ECS) mapping. The software analyses task-related changes in gamma activity recorded from implanted subdural electrocorticography electrodes using extensions to previously published methods. In this manuscript, we describe the system's architecture and workflow required to obtain a map of the eloquent cortex. We validate the system by comparing our mapping results with those acquired using ECS mapping in two subjects. Our results indicate that cortiQ reliably identifies eloquent cortex much faster (several minutes compared to an hour or more) than ECS mapping. Next-neighbour analyses show that there are no false positives and an average of 1.24% false negatives.


Subject(s)
Brain Mapping/methods , Electroencephalography , Software , Brain Mapping/instrumentation , Electric Stimulation , Electrodes, Implanted , Epilepsy/physiopathology , Humans
15.
J Neuropathol Exp Neurol ; 72(9): 884-91, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23965747

ABSTRACT

To identify pathologic characteristics that are associated with outcome, we performed a retrospective analysis of the clinical, radiologic, and pathologic features of 44 children with isolated focal cortical dysplasia (FCD) after epilepsy surgery. Based on the International League Against Epilepsy Classification, 16 patients had FCD Type I and 28 subjects had FCD Type II. A significantly higher percentage of subjects with FCD Type IIb versus Types I and IIa were seizure-free after surgery. Akt (also known as protein kinase B) is the main downstream target of phosphatidylinositol 3'-kinase and has been implicated in epilepsy pathogenesis. Semiquantitative analysis of cortical gliosis and quantitation of Akt1-immunoreactive neurons indicated that individuals with FCD Type II were more likely to have diffuse astrogliosis and higher counts of Akt1-positive neurons versus those with FCD Type I. A logistic regression model, including Akt1-positive neurons, age at surgery, and the interaction of these factors, was significantly associated with seizure-free outcome. This study provides evidence that astrogliosis and overexpression of neuronal Akt1 protein may be important factors in the pathogenesis of FCD and suggests that the pathogenesis of FCD Type I may differ from that of FCD Type II in children.


Subject(s)
Aging , Brain Diseases/pathology , Cerebral Cortex/pathology , Malformations of Cortical Development/pathology , Neurons/metabolism , Postoperative Complications/pathology , Proto-Oncogene Proteins c-akt/metabolism , Adolescent , Brain Diseases/classification , Brain Diseases/diagnostic imaging , Brain Diseases/etiology , Cell Count , Cerebral Cortex/diagnostic imaging , Child , Child, Preschool , Epilepsy/surgery , Female , Fluorodeoxyglucose F18 , Follow-Up Studies , Glial Fibrillary Acidic Protein , Humans , Infant , Magnetic Resonance Imaging , Male , Malformations of Cortical Development/classification , Malformations of Cortical Development/diagnostic imaging , Malformations of Cortical Development/etiology , Malformations of Cortical Development, Group I , Positron-Emission Tomography , Postoperative Complications/etiology , Retrospective Studies , Statistics, Nonparametric
16.
Epilepsy Res ; 92(1): 63-73, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20863661

ABSTRACT

PURPOSE: We aimed to determine the changes in neural correlates of auditory information processing such as auditory detection, encoding, and sensory discrimination in pediatric patients with intractable epilepsy. METHODS: In this magnetoencephalography (MEG) study, 10 patients and 10 age- and gender-matched healthy controls were investigated with the multi-feature mismatch negativity (MMN) paradigm. Latencies and amplitudes of M100, M150, M200, and MMN event-related fields were evaluated. RESULTS: All event-related fields in response to standard stimuli (M100, M150 and M200) and responses to occasional five deviant sounds, deviating from the standard stimuli either in duration, frequency, intensity, location, or by including a silent gap were reduced in amplitude in epilepsy patients compared with healthy controls. CONCLUSIONS: Our study suggests that auditory information processing is impaired in patients with drug-resistant epilepsy, being evident both in stimulus feature encoding (as reflected by changes of early event-related components, e.g., M100) and in cortical sound discrimination (as reflected by MMNm). The neural changes involving diminished M100 as well as MMNms for all five deviant sound types suggest wide-spread auditory information processing impairments in these patients.


Subject(s)
Auditory Cortex/physiopathology , Brain Mapping , Cognition Disorders/etiology , Epilepsy/complications , Epilepsy/pathology , Evoked Potentials, Auditory/physiology , Acoustic Stimulation/methods , Adolescent , Case-Control Studies , Child , Contingent Negative Variation/physiology , Disease Progression , Female , Functional Laterality , Humans , Intelligence/physiology , Magnetoencephalography/methods , Male , Neuropsychological Tests , Pediatrics , Statistics as Topic
18.
Pediatr Neurosurg ; 43(3): 202-8, 2007.
Article in English | MEDLINE | ID: mdl-17409789

ABSTRACT

OBJECTIVE: The purpose of this study was to evaluate seizure outcome in children with intractable secondary generalized epilepsy without a resectable focus who underwent complete corpus callosotomy and compare these results to those of anterior two-third callosotomy. METHOD: Data were obtained for all patients who underwent a corpus callosotomy from 2000 to 2005. The study involved 37 patients. Eleven patients had anterior two-third corpus callosotomy compared with 28 patients who underwent complete corpus callosotomy. Two of these patients had completion of their callosotomy following initial partial callosotomy. Seizure type, seizure frequency, and family satisfaction were evaluated for all patients pre- and postoperatively. RESULTS: A reduction of >or=75% in seizures occurred in 75% of the total-callosotomy patients compared to 55% of the partial-callosotomy patients. Family satisfaction for complete and partial callosotomy was 89 and 73%, respectively. No prolonged neurologic deficits were observed in either group. CONCLUSION: Complete corpus callosotomy is the most effective treatment for secondary generalized intractable seizures not amenable to focal resection in children.


Subject(s)
Corpus Callosum/surgery , Epilepsy, Generalized/surgery , Epilepsy, Tonic-Clonic/surgery , Child , Child, Preschool , Craniotomy , Epilepsies, Myoclonic/diagnosis , Epilepsies, Myoclonic/surgery , Epilepsy, Absence/diagnosis , Epilepsy, Absence/surgery , Epilepsy, Complex Partial/diagnosis , Epilepsy, Complex Partial/surgery , Epilepsy, Generalized/diagnosis , Epilepsy, Tonic-Clonic/diagnosis , Female , Follow-Up Studies , Humans , Infant , Male , Postoperative Complications/etiology , Surgical Instruments
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