Screening for lung cancer: 2023 guideline update from the American Cancer Society.

Lung cancer is the leading cause of mortality and person-years of life lost from cancer among US men and women. Early detection has been shown to be associated with reduced lung cancer mortality. Our objective was to update the American Cancer Society (ACS) 2013 lung cancer screening (LCS) guideline for adults at high risk for lung cancer. The guideline is intended to provide guidance for screening to health care providers and their patients who are at high risk for lung cancer due to a history of smoking. The ACS Guideline Development Group (GDG) utilized a systematic review of the LCS literature commissioned for the US Preventive Services Task Force 2021 LCS recommendation update; a second systematic review of lung cancer risk associated with years since quitting smoking (YSQ); literature published since 2021; two Cancer Intervention and Surveillance Modeling Network-validated lung cancer models to assess the benefits and harms of screening; an epidemiologic and modeling analysis examining the effect of YSQ and aging on lung cancer risk; and an updated analysis of benefit-to-radiation-risk ratios from LCS and follow-up examinations. The GDG also examined disease burden data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program. Formulation of recommendations was based on the quality of the evidence and judgment (incorporating values and preferences) about the balance of benefits and harms. The GDG judged that the overall evidence was moderate and sufficient to support a strong recommendation for screening individuals who meet the eligibility criteria. LCS in men and women aged 50-80 years is associated with a reduction in lung cancer deaths across a range of study designs, and inferential evidence supports LCS for men and women older than 80 years who are in good health. The ACS recommends annual LCS with low-dose computed tomography for asymptomatic individuals aged 50-80 years who currently smoke or formerly smoked and have a ≥20 pack-year smoking history (strong recommendation, moderate quality of evidence). Before the decision is made to initiate LCS, individuals should engage in a shared decision-making discussion with a qualified health professional. For individuals who formerly smoked, the number of YSQ is not an eligibility criterion to begin or to stop screening. Individuals who currently smoke should receive counseling to quit and be connected to cessation resources. Individuals with comorbid conditions that substantially limit life expectancy should not be screened. These recommendations should be considered by health care providers and adults at high risk for lung cancer in discussions about LCS. If fully implemented, these recommendations have a high likelihood of significantly reducing death and suffering from lung cancer in the United States.

Epilepsy surgery as a treatment option for select patients with PCDH19-related epilepsy.

PCDH19 is a common epilepsy gene causing medication resistant epilepsy with fever-related seizures. Traditionally, patients with PCDH19-related epilepsy have not been considered surgical candidates. This retrospective review evaluated three patients with pathogenic variants in PCDH19 who presented with seizures in childhood, had one seizure semiology, became medication resistant, and had concordant imaging, seizure semiology and electrographic findings. All three patients ultimately underwent temporal lobectomy, resulting in seizure freedom. These findings suggest epilepsy surgery can be an effective treatment option for select patients with PCDH19-related epilepsy and a single seizure semiology.

Intact speech perception after resection of dominant hemisphere primary auditory cortex for the treatment of medically refractory epilepsy: illustrative case.

BACKGROUND: In classic speech network models, the primary auditory cortex is the source of auditory input to Wernicke's area in the posterior superior temporal gyrus (pSTG). Because resection of the primary auditory cortex in the dominant hemisphere removes inputs to the pSTG, there is a risk of speech impairment. However, recent research has shown the existence of other, nonprimary auditory cortex inputs to the pSTG, potentially reducing the risk of primary auditory cortex resection in the dominant hemisphere. OBSERVATIONS: Here, the authors present a clinical case of a woman with severe medically refractory epilepsy with a lesional epileptic focus in the left (dominant) Heschl's gyrus. Analysis of neural responses to speech stimuli was consistent with primary auditory cortex localization to Heschl's gyrus. Although the primary auditory cortex was within the proposed resection margins, she underwent lesionectomy with total resection of Heschl's gyrus. Postoperatively, she had no speech deficits and her seizures were fully controlled. LESSONS: While resection of the dominant hemisphere Heschl's gyrus/primary auditory cortex warrants caution, this case illustrates the ability to resect the primary auditory cortex without speech impairment and supports recent models of multiple parallel inputs to the pSTG.

Association of Body Mass Index in Midlife With Morbidity Burden in Older Adulthood and Longevity.

Importance: Abundant evidence links obesity with adverse health consequences. However, controversies persist regarding whether overweight status compared with normal body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) is associated with longer survival and whether this occurs at the expense of greater long-term morbidity and health care expenditures. Objective: To examine the association of BMI in midlife with morbidity burden, longevity, and health care expenditures in adults 65 years and older. Design, Setting, and Participants: Prospective cohort study at the Chicago Heart Association Detection Project in Industry, with baseline in-person examination between November 1967 and January 1973 linked with Medicare follow-up between January 1985 and December 2015. Participants included 29 621 adults who were at least age 65 years in follow-up and enrolled in Medicare. Data were analyzed from January 2020 to December 2021. Exposures: Standard BMI categories. Main Outcomes and Measures: (1) Morbidity burden at 65 years and older assessed with the Gagne combined comorbidity score (ranging from -2 to 26, with higher score associated with higher mortality), which is a well-validated index based on International Classification of Diseases, Ninth Revision codes for use in administrative data sets; (2) longevity (age at death); and (3) health care costs based on Medicare linkage in older adulthood (aged ≥65 years). Results: Among 29 621 participants, mean (SD) age was 40 (12) years, 57.1% were men, and 9.1% were Black; 46.0% had normal BMI, 39.6% were overweight, and 11.9% had classes I and II obesity at baseline. Higher cumulative morbidity burden in older adulthood was observed among those who were overweight (7.22 morbidity-years) and those with classes I and II obesity (9.80) compared with those with a normal BMI (6.10) in midlife (P < .001). Mean age at death was similar between those who were overweight (82.1 years [95% CI, 81.9-82.2 years]) and those who had normal BMI (82.3 years [95% CI, 82.1-82.5 years]) but shorter in those who with classes I and II obesity (80.8 years [95% CI, 80.5-81.1 years]). The proportion (SE) of life-years lived in older adulthood with Gagne score of at least 1 was 0.38% (0.00%) in those with a normal BMI, 0.41% (0.00%) in those with overweight, and 0.43% (0.01%) in those with classes I and II obesity. Cumulative median per-person health care costs in older adulthood were significantly higher among overweight participants ($12 390 [95% CI, $10 427 to $14 354]) and those with classes I and II obesity ($23 396 [95% CI, $18 474 to $28 319]) participants compared with those with a normal BMI (P < .001). Conclusions and Relevance: In this cohort study, overweight in midlife, compared with normal BMI, was associated with higher cumulative burden of morbidity and greater proportion of life lived with morbidity in the context of similar longevity. These findings translated to higher total health care expenditures in older adulthood for those who were overweight in midlife.

A research protocol for a pilot, randomized controlled trial designed to examine the feasibility of a dyadic versus individual yoga program for family caregivers of glioma patients undergoing radiotherapy.

BACKGROUND: Although the diagnosis and treatment of a primary brain tumor present unique challenges to patients and their family caregivers, evidence-based supportive care interventions are generally lacking. The primary aim of this research protocol is to determine the feasibility of implementing a dyadic yoga (DY) versus a caregiver yoga (CY) intervention or a wait-list control (WLC) group using a randomized controlled trial design. METHODS: Seventy-five glioma patients undergoing radiotherapy and their family caregivers are randomized to the DY, CY, or a WLC group. Patient-caregiver dyads in the DY group and caregivers in the CY group receive 15 sessions (45 min each) over the course of patients' standard radiotherapy (6 weeks). Patients and caregivers in all groups complete baseline assessments of symptoms, quality of life (QOL), and health utilization outcomes prior to randomization. Follow-up assessments are performed 6 weeks and then again 3 months later. The primary outcome is feasibility (i.e., ≥ 50% of eligible dyads consent, ≥ 70% of enrolled dyads complete all assessments, and ≥ 50% of all practice sessions are attended). We will also perform primarily descriptive analyses of the self-reported outcomes (e.g., fatigue, overall QOL) and explore potential intervention moderators (e.g., performance status) to inform a larger future trial. CONCLUSION: This trial will provide important information regarding the feasibility of a dyadic versus a caregiver yoga intervention regarding symptom, QOL, and health utilization outcomes in glioma patients and their caregivers. TRIAL REGISTRATION: ClinicalTrials.gov NCT02481349.

Cancer-Related Risk Perceptions and Beliefs in Texas: Findings from a 2018 Population-Level Survey.

BACKGROUND: Cancer beliefs and perceptions of cancer risk affect the cancer continuum. Identifying underlying factors associated with these beliefs and perceptions in Texas can help inform and target prevention efforts. METHODS: We developed a cancer-focused questionnaire and administered it online to a nonprobability sample of the Texas population. Weighted multivariable logistic regression analysis identified key factors associated with perceptions and beliefs about cancer. RESULTS: The study population comprised 2,034 respondents (median age, 44.4 years) of diverse ethnicity: 45.5% were non-Hispanic white, 10.6% non-Hispanic black, and 35.7% Hispanic. Self-reported depression was significantly associated with cancer risk perceptions and cancer beliefs. Those indicating frequent and infrequent depression versus no depression were more likely to believe that: (i) compared to other people their age, they were more likely to get cancer in their lifetime [OR, 2.92; 95% confidence interval (CI), 1.95-4.39 and OR, 1.79; 95% CI, 1.17-2.74, respectively]; and (ii) when they think about cancer, they automatically think about death (OR, 2.05; 95% CI, 1.56-2.69 and OR, 1.46; 95% CI, 1.11-1.92, respectively). Frequent depression versus no depression was also associated with agreement that (i) it seems like everything causes cancer (OR, 1.67; 95% CI, 1.26-2.22) and (ii) there is not much one can do to lower one's chance of getting cancer (OR, 1.44; 95% CI, 1.09-1.89). Other predictors for perceived cancer risk and/or cancer beliefs were sex, age, ethnicity/race, being born in the United States, marital status, income, body mass index, and smoking. CONCLUSIONS: Depression and other predictors are associated with cancer risk perceptions and beliefs in Texas. IMPACT: Increased attention to reducing depression may improve cancer risk perceptions and beliefs.

Epigenetic targeting DNMT1 of pancreatic ductal adenocarcinoma using interstitial control release biodegrading polymer reduced tumor growth through hedgehog pathway inhibition.

Annually, 48,000 people die from pancreatic ductal adenocarcinoma (PDAC), ranking it the fourth among cancer-related deaths in the United States. Currently, anti-cancer drugs are not effective against PDAC, and only extends survival by 3 months. Aberrant DNA methylation has been shown to play an important role during carcinogenesis in PDAC, with approximately 80% of tumor overexpressing the DNA methyltransferase 1 (DNMT1) protein. In the present study, we used DNMTs as a screening platform to find a new DNMT inhibitor, n-butylidenephthalide (n-BP), which is identified from a Chinese herbal drug. n-BP could inhibit DNMT1 expression in both dose-dependent and time-dependent manner. It also displays an effect in suppressing growth of PDAC cells and inducing cell cycle arrest at G0/G1 phase leading apoptosis. Growth suppression can be restored by the overexpression of DNMT1 in PDAC cells. Furthermore, we found n-BP-mediated DNMT1 suppression influenced the protein stability rather than changing the RNA expression. Through microarray studies, we found that the patched domain contained 4 (PTCHD4) is the potential downstream gene of DNMT1. Following silencing of PTCHD4 expression by siRNA, n-BP decreased tumor growth inhibition. Finally, in vivo, two animal models were used to evaluate the efficacy and survival after n-BP treatment by interstitial control release polymer delivery. The results show that n-BP could effectively inhibit PDAC tumor volume growth and extend animal survival. In summary, n-BP may inhibit the growth of human PDAC cells though reducing DNMT1 and increasing the expression of PTCHD4 both in vitro and in vivo.

Mesenchymal Stem Cell Therapy of Pulmonary Fibrosis: Improvement with Target Combination.

Although the clinical application of new drugs has been shown to be effective in slowing disease progression and improving the quality of life in patients with pulmonary fibrosis, the damaged lung tissue does not recover with these drugs. Thus, there is an urgent need to establish regenerative therapy, such as stem cell therapy or tissue engineering. Moreover, the clinical application of mesenchymal stem cell (MSC) therapy has been shown to be safe in humans with idiopathic pulmonary fibrosis (IPF). It seems that a combination of MSC transplantation and pharmaceutical therapy might have additional benefits; however, the experimental design for its efficacy is still lacking. In this review, we provide an overview of the mechanisms that were identified when IPF was treated with MSC transplantation or new drugs. To maximize the therapeutic effect, we suggest that MSC transplantation is combined with drug application for synergistic effects. This review provides clinicians and scientists with the most efficient medical options, in the hope that this will spur on future research and lead to an eventual cure for this disease.

Trends in the Incidence, Prevalence, and Survival Outcomes in Patients With Neuroendocrine Tumors in the United States.

IMPORTANCE: The incidence and prevalence of neuroendocrine tumors (NETs) are thought to be rising, but updated epidemiologic data are lacking. OBJECTIVE: To explore the evolving epidemiology and investigate the effect of therapeutic advances on survival of patients with NETs. DESIGN, SETTING, AND PARTICIPANTS: A retrospective, population-based study using nationally representative data from the Surveillance, Epidemiology, and End Results (SEER) program was conducted to evaluate 64 971 patients with NETs from 1973 to 2012. Associated population data were used to determine annual age-adjusted incidence, limited-duration prevalence, and 5-year overall survival (OS) rates. Trends in survival from 2000 to 2012 were evaluated for the entire cohort as well as specific subgroups, including distant-stage gastrointestinal NETs and pancreatic NETs. Analyses were conducted between December 2015, and February 2017. MAIN OUTCOMES AND MEASURES: Neuroendocrine tumor incidence, prevalence, and OS rates. RESULTS: Of the 64 971 cases of NETs, 34 233 (52.7%) were women. The age-adjusted incidence rate increased 6.4-fold from 1973 (1.09 per 100 000) to 2012 (6.98 per 100 000). This increase occurred across all sites, stages, and grades. In the SEER 18 registry grouping (2000-2012), the highest incidence rates were 1.49 per 100 000 in the lung, 3.56 per 100 000 in gastroenteropancreatic sites, and 0.84 per 100 000 in NETs with an unknown primary site. The estimated 20-year limited-duration prevalence of NETs in the United States on January 1, 2014, was 171 321. On multivariable analyses, the median 5-year OS rate varied significantly by stage, grade, age at diagnosis, primary site, and time period of diagnosis. The OS rate for all NETs improved from the 2000-2004 period to the 2009-2012 period (hazard ratio [HR], 0.79; 95% CI, 0.73-0.85). Even larger increases in OS between these periods were noted in distant-stage gastrointestinal NETs (HR, 0.71; 95% CI, 0.62-0.81) and distant-stage pancreatic NETs (HR, 0.56; 95% CI, 0.44-0.70). CONCLUSIONS AND RELEVANCE: The incidence and prevalence of NETs are steadily rising, possibly owing to detection of early-stage disease and stage migration. Survival for all NETs has improved over time, especially for distant-stage gastrointestinal NETs and pancreatic NETs in particular, reflecting improvement in therapies. These data will help to prioritize future research directions.

Influence of Surveillance PET/CT on Detection of Early Recurrence After Definitive Radiation in Stage III Non-small-cell Lung Cancer.

BACKGROUND: There are few data to support the use of varying imaging modalities in evaluating recurrence in non-small-cell lung cancer (NSCLC). We compared the efficacy of surveillance positron emission tomography (PET)/computed tomography (CT) versus CT scans of the chest in detecting recurrences after definitive radiation for NSCLC. MATERIALS AND METHODS: We retrospectively analyzed 200 patients treated between 2000 and 2011 who met the inclusion criteria of stage III NSCLC, completion of definitive radiation treatment, and absence of recurrence within the initial 6 months. These patients were then grouped on the basis of the use of PET/CT imaging during postradiation surveillance. Patients who received ≥ 1 PET/CT scans within 6 months of the end of radiation treatment were placed in the PET group whereas all others were placed in the CT group. We compared survival times from the end of treatment to the date of death or last follow-up using log rank tests. Multivariate analysis was conducted to identify factors associated with decreased survival. RESULTS: In the entire cohort, median event-free survival (EFS) was 26.7 months, and median overall survival (OS) was 41.2 months. The CT group had a median EFS of 21.4 months versus 29.4 months for the PET group (P = .59). There was no difference in OS between the CT and PET groups (median OS of 41.2 and 41.3 months, respectively; P = .59). There was also no difference in local recurrence-free survival or distant metastases-free survival between the CT-only and PET/CT groups (P = .92 and P = .30, respectively). Similarly, in multivariate analysis, stratification into the PET group was not associated with improved EFS (hazard ratio [HR], 0.90; 95% confidence interval [CI], 0.61-1.34; P = .60) or OS (HR, 1.2; 95% CI, 0.83-1.7; P = .34). CONCLUSIONS: In stage III NSCLC patients treated with definitive radiation and without early recurrence, PET/CT scan surveillance did not result in decreased time to detection of locoregional or distant recurrence or improved survival.

Design architectures for optically multiplexed imaging.

Optically multiplexed imaging is the process by which multiple images are overlaid on a single image surface. Uniquely encoding the discrete images allows scene reconstruction from multiplexed images via post processing. We describe a class of optical systems that can achieve high density image multiplexing through a novel division of aperture technique. Fundamental design considerations and performance attributes for this sensor architecture are discussed. A number of spatial and temporal encoding methods are presented including point spread function engineering, amplitude modulation, and image shifting. Results from a prototype five-channel sensor are presented using three different encoding methods in sparse-scene star tracking demonstration. A six-channel optically multiplexed prototype sensor is used to reconstruct imagery from information rich dense scenes through dynamic image shifting.

Transient aphasias after left hemisphere resective surgery.

OBJECT: Transient aphasias are often observed in the first few days after a patient has undergone resection in the language-dominant hemisphere. The aims of this prospective study were to characterize the incidence and nature of these aphasias and to determine whether there are relationships between location of the surgical site and deficits in specific language domains. METHODS: One hundred ten patients undergoing resection to the language-dominant hemisphere participated in the study. Language was evaluated prior to surgery and 2-3 days and 1 month postsurgery using the Western Aphasia Battery and the Boston Naming Test. Voxel-based lesion-symptom mapping was used to identify relationships between the surgical site location assessed on MRI and deficits in fluency, information content, comprehension, repetition, and naming. RESULTS: Seventy-one percent of patients were classified as aphasic based on the Western Aphasia Battery 2-3 days postsurgery, with deficits observed in each of the language domains examined. Fluency deficits were associated with resection of the precentral gyrus and adjacent inferior frontal cortex. Reduced information content of spoken output was associated with resection of the ventral precentral gyrus and posterior inferior frontal gyrus (pars opercularis). Repetition deficits were associated with resection of the posterior superior temporal gyrus. Naming deficits were associated with resection of the ventral temporal cortex, with midtemporal and posterior temporal damage more predictive of naming deficits than anterior temporal damage. By 1 month postsurgery, nearly all language deficits were resolved, and no language measure except for naming differed significantly from its presurgical level. CONCLUSIONS: These findings show that transient aphasias are very common after left hemisphere resective surgery and that the precise nature of the aphasia depends on the specific location of the surgical site. The patient cohort in this study provides a unique window into the neural basis of language because resections are discrete, their locations are not limited by vascular distribution or patterns of neurodegeneration, and language can be studied prior to substantial reorganization.

Enzyme-inducing anticonvulsants increase plasma clearance of dexmedetomidine: a pharmacokinetic and pharmacodynamic study.

BACKGROUND: Dexmedetomidine is useful during mapping of epileptic foci as it facilitates electrocorticography unlike most other anesthetic agents. Patients with seizure disorders taking enzyme-inducing anticonvulsants appear to be resistant to its sedative effects. The objective of the study was to compare the pharmacokinetic and pharmacodynamic profile of dexmedetomidine in healthy volunteers with volunteers with seizure disorders receiving enzyme-inducing anticonvulsant medications. METHODS: Dexmedetomidine was administered using a step-wise, computer-controlled infusion to healthy volunteers (n = 8) and volunteers with seizure disorders (n = 8) taking phenytoin or carbamazapine. Sedation and dexmedetomidine plasma levels were assessed at baseline, during the infusion steps, and after discontinuation of the infusion. Sedation was assessed by using the Observer's Assessment of Alertness/Sedation Scale, Ramsay Sedation Scale, and Visual Analog Scale and processed electroencephalography (entropy) monitoring. Pharmacokinetic analysis was performed on both groups, and differences between groups were determined using the standard two-stage approach. RESULTS: A two-compartment model was fit to dexmedetomidine concentration-time data. Dexmedetomidine plasma clearance was 43% higher in the seizure group compared with the control group (42.7 vs. 29.9 l/h; P = 0.007). In contrast, distributional clearance and the volume of distribution of the central and peripheral compartments were similar between the groups. No difference in sedation was detected between the two groups during a controlled range of target plasma concentrations. CONCLUSION: This study demonstrates that subjects with seizure disorders taking enzyme-inducing anticonvulsant medications have an increased plasma clearance of dexmedetomidine as compared with healthy control subjects.

Seizures and epileptiform activity in the early stages of Alzheimer disease.

IMPORTANCE: Epileptic activity associated with Alzheimer disease (AD) deserves increased attention because it has a harmful impact on these patients, can easily go unrecognized and untreated, and may reflect pathogenic processes that also contribute to other aspects of the illness. We report key features of AD-related seizures and epileptiform activity that are instructive for clinical practice and highlight similarities between AD and transgenic animal models of the disease. OBJECTIVE: To describe common clinical characteristics and treatment outcomes of patients with amnestic mild cognitive impairment (aMCI) or early AD who also have epilepsy or subclinical epileptiform activity. DESIGN: Retrospective observational study from 2007 to 2012. SETTING Memory and Aging Center, University of California, San Francisco. PATIENTS: We studied 54 patients with a diagnosis of aMCI plus epilepsy (n = 12), AD plus epilepsy (n = 35), and AD plus subclinical epileptiform activity (n = 7). MAIN OUTCOMES AND MEASURES: Clinical and demographic data, electroencephalogram (EEG) readings, and treatment responses to antiepileptic medications. RESULTS: Patients with aMCI who had epilepsy presented with symptoms of cognitive decline 6.8 years earlier than patients with aMCI who did not have epilepsy (64.3 vs 71.1 years; P = .02). Patients with AD who had epilepsy presented with cognitive decline 5.5 years earlier than patients with AD who did not have epilepsy (64.8 vs 70.3 years; P = .001). Patients with AD who had subclinical epileptiform activity also had an early onset of cognitive decline (58.9 years). The timing of seizure onset in patients with aMCI and AD was nonuniform (P < .001), clustering near the onset of cognitive decline. Epilepsies were most often complex partial seizures (47%) and more than half were nonconvulsive (55%). Serial or extended EEG monitoring appeared to be more effective than routine EEG at detecting interictal and subclinical epileptiform activity. Epileptic foci were predominantly unilateral and temporal. Of the most commonly prescribed antiepileptics, treatment outcomes appeared to be better for lamotrigine and levetiracetam than for phenytoin. CONCLUSIONS AND RELEVANCE: Common clinical features of patients with aMCI- or AD-associated epilepsy at our center included early age at onset of cognitive decline, early incidence of seizures in the disease course, unilateral temporal epileptic foci detected by serial/extended EEG, transient cognitive dysfunction, and good seizure control and tolerability with lamotrigine and levetiracetam. Careful identification and treatment of epilepsy in such patients may improve their clinical course.

Comparison of seizure control outcomes and the safety of vagus nerve, thalamic deep brain, and responsive neurostimulation: evidence from randomized controlled trials.

Epilepsy is a devastating disease, often refractory to medication and not amenable to resective surgery. For patients whose seizures continue despite the best medical and surgical therapy, 3 stimulation-based therapies have demonstrated positive results in prospective randomized trials: vagus nerve stimulation, deep brain stimulation of the thalamic anterior nucleus, and responsive neurostimulation. All 3 neuromodulatory therapies offer significant reductions in seizure frequency for patients with partial epilepsy. A direct comparison of trial results, however, reveals important differences among outcomes and surgical risk between devices. The authors review published results from these pivotal trials and highlight important differences between the trials and devices and their application in clinical use.

Rates and predictors of long-term seizure freedom after frontal lobe epilepsy surgery: a systematic review and meta-analysis.

OBJECT: Frontal lobe epilepsy (FLE) is the second-most common focal epilepsy syndrome, and seizures are medically refractory in many patients. Although various studies have examined rates and predictors of seizure freedom after resection for FLE, there is significant variability in their results due to patient diversity, and inadequate follow-up may lead to an overestimation of long-term seizure freedom. METHODS: In this paper the authors report a systematic review and meta-analysis of long-term seizure outcomes and predictors of response after resection for intractable FLE. Only studies of at least 10 patients examining seizure freedom after FLE surgery with postoperative follow-up duration of at least 48 months were included. RESULTS: Across 1199 patients in 21 studies, the overall rate of postoperative seizure freedom (Engel Class I outcome) was 45.1%. No trend in seizure outcomes across all studies was observed over time. Significant predictors of long-term seizure freedom included lesional epilepsy origin (relative risk [RR] 1.67, 95% CI 1.36-28.6), abnormal preoperative MRI (RR 1.64, 95% CI 1.32-2.08), and localized frontal resection versus more extensive lobectomy with or without an extrafrontal component (RR 1.71, 95% CI 1.26-2.43). Within lesional FLE cases, gross-total resection led to significantly improved outcome versus subtotal lesionectomy (RR 1.99, 95% CI 1.47-2.84). CONCLUSIONS: These findings suggest that FLE patients with a focal and identifiable lesion are more likely to achieve seizure freedom than those with a more poorly defined epileptic focus. While seizure freedom can be achieved in the surgical treatment of medically refractory FLE, these findings illustrate the compelling need for improved noninvasive and invasive localization techniques in FLE.

Associates of stigma in an incident epilepsy population from northern Manhattan, New York City.

OBJECTIVE: Stigma is associated with prevalent epilepsy, but its association with incident epilepsy is unknown. METHODS: We identified 209 children and adults with incident seizures from the diverse impoverished community of northern Manhattan. We interviewed 94 participants, aged 16 and older, about lifetime history of depression, health status, medical history, and stigma. RESULTS: At baseline, 18 (22.5%) participants reported experiencing stigma. Stigma was reported by 9 (50.0%) with depression and 9 (14.5%) without depression (P=0.002). At 1 year, 7 (8.1%) participants reported experiencing stigma. Stigma was reported by 5 (31.3%) with depression versus 1 (1.6%) without depression (P<0.0001). At both time points, odds of stigma increased when lifetime history of depression and fair/poor health was present. CONCLUSIONS: Previous work revealed negative effects of prevalent epilepsy on stigma. In the low-income, predominantly Hispanic community of northern Manhattan, we found incident epilepsy was associated with stigma when lifetime history of depression or fair/poor health was present.

Evaluation of the patient with spells.

PURPOSE OF REVIEW: : The neurologic consultant is frequently called to evaluate the patient with transient neurologic deficits, or spells. Spells can present with a broad array of clinical features, making a systematic evaluation challenging. Familiarity with a variety of key features for different spell types will help the consultant create an appropriate differential diagnosis to guide the diagnostic evaluation. RECENT FINDINGS: : Recent practice parameters outline the appropriate evaluation for patients presenting with first unprovoked seizure, and an update in the International League Against Epilepsy classification scheme for seizures has shifted the terminology used to describe these spells. When a spell cannot be unambiguously identified as a seizure, recent studies propose features to help distinguish syncope, sleep disorders, and psychogenic nonepileptic seizures. For patients who are critically ill, extended EEG monitoring is increasingly available, and there is a growing appreciation for the high burden of seizures and status epilepticus in the intensive care unit population. SUMMARY: : This article reviews the most common paroxysmal spell types encountered on the acute care ward and in the intensive care unit, discusses clinical features that help distinguish various spell types, and proposes a systematic evaluation for use by the neurologic consultant.

Underlying cause of death in incident unprovoked seizures in the urban community of Northern Manhattan, New York City.

We determined underlying cause-specific mortality for incident unprovoked seizures from Northern Manhattan, New York City. We calculated the case fatality, proportionate mortality, and the underlying cause-specific standardized mortality ratios (SMRs), with U.S. death rates as the standard. Thirty-two deaths were observed between 2003 and 2007 among 209 participants. Case fatality was significantly lower for idiopathic/cryptogenic seizures versus symptomatic seizures. About 31.3% of the deaths were attributed to malignant neoplasms, 25.0% to diseases of the heart, 15.6% to influenza and pneumonia, 3.1% to cerebrovascular diseases, and 25.0% to other causes. Significant SMRs were observed for all causes (SMR = 1.6), influenza and pneumonia (SMR = 7.1), and malignant neoplasms (SMR = 2.9). Younger cases (<65 years) had increased SMRs for all causes, malignant neoplasms, and other causes. Older cases (> or =65 years) had increased SMRs for influenza and pneumonia. Underlying cause of death paralleled the underlying cause of seizure in patients with symptomatic etiologies.