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OBJECTIVE: Epilepsy is a common neurological disorder affecting 1% of the global population. Loss of consciousness in focal impaired awareness seizures (FIASs) and focal-to-bilateral tonic-clonic seizures (FBTCSs) can be devastating, but the mechanisms are not well understood. Although ictal activity and interictal connectivity changes have been noted, the network states of focal aware seizures (FASs), FIASs, and FBTCSs have not been thoroughly evaluated with network measures ictally. METHODS: We obtained electrographic data from 74 patients with stereoelectroencephalography (SEEG). Sliding window band power, functional connectivity, and segregation were computed on preictal, ictal, and postictal data. Five-minute epochs of wake, rapid eye movement sleep, and deep sleep were also extracted. Connectivity of subcortical arousal structures was analyzed in a cohort of patients with both SEEG and functional magnetic resonance imaging (fMRI). Given that custom neuromodulation of seizures is predicated on detection of seizure type, a convolutional neural network was used to classify seizure types. RESULTS: We found that in the frontoparietal association cortex, an area associated with consciousness, both consciousness-impairing seizures (FIASs and FBTCSs) and deep sleep had increases in slow wave delta (1-4 Hz) band power. However, when network measures were employed, we found that only FIASs and deep sleep exhibited an increase in delta segregation and a decrease in gamma segregation. Furthermore, we found that only patients with FIASs had reduced subcortical-to-neocortical functional connectivity with fMRI versus controls. Finally, our deep learning network demonstrated an area under the curve of .75 for detecting consciousness-impairing seizures. SIGNIFICANCE: This study provides novel insights into ictal network measures in FASs, FIASs, and FBTCSs. Importantly, although both FIASs and FBTCSs result in loss of consciousness, our results suggest that ictal network changes in FIASs uniquely resemble those that occur during deep sleep. Our results may inform novel neuromodulation strategies for preservation of consciousness in epilepsy.
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OBJECTIVE: To review clinical and neuropsychological characteristics and natural history of a series of patients with temporal lobe epilepsy (TLE) and anterior temporal encephaloceles (ATE) and compare them to a similar series of TLE patients with mesial temporal sclerosis (MTS) to identify characteristics suggestive of ATE-related epilepsy. METHODS: Patients with epilepsy and ATE were identified via clinic encounters and consensus epilepsy surgery conference at a Level 4 epilepsy center. The drug-resistant subset of these patients who underwent epilepsy surgery (twenty-two of thirty-five) were compared to age- and laterality-matched patients with MTS. Clinical, neuropsychological, electrophysiologic, and surgical data were abstracted through chart review. RESULTS: In comparison with MTS, ATE patients were more often female, had significantly later onset of epilepsy, and did not have prior febrile seizures. In addition, ATE patients were more likely to have chronic headaches and other historical features consistent with idiopathic intracranial hypertension (IIH). Failure to identify ATE on initial imaging was common. Most patients had limited temporal cortical resections sparing mesial structures. Of the twenty ATE patients who had a long-term postsurgical follow-up, seventeen (85%) had International League Against Epilepsy (ILAE) Class 1 or 2 outcomes. SIGNIFICANCE: A shorter duration of epilepsy, female gender, and lack of history of febrile seizures may suggest ATE as an etiology of refractory TLE in adults. Targeted encephalocele resections can result in seizure freedom, underscoring the importance of encephalocele identification.
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Epilepsia do Lobo Temporal , Esclerose Hipocampal , Convulsões Febris , Adulto , Feminino , Humanos , Encefalocele/complicações , Encefalocele/diagnóstico por imagem , Epilepsia do Lobo Temporal/complicações , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/cirurgia , Imageamento por Ressonância Magnética , Estudos Retrospectivos , Esclerose/complicações , Convulsões Febris/complicações , Resultado do Tratamento , MasculinoRESUMO
PURPOSE: To characterize the relationship between functional seizures (FSe), cerebrovascular disease (CVD), and functional stroke. METHOD: A retrospective case-control study of 189 patients at a single large tertiary medical center. We performed a manual chart review of medical records of patients with FSe or epileptic seizures (ES), who also had ICD code evidence of CVD. The clinical characteristics of FSe, ES, CVD, and functional stroke were recorded. Logistic regression and Welch's t-tests were used to evaluate the differences between the FSe and ES groups. RESULTS: Cerebrovascular disease was confirmed in 58.7% and 87.6% of patients with FSe or ES through manual chart review. Stroke was significantly more common in patients with ES (76.29%) than FSe (43.48%) (pâ¯=â¯4.07â¯×â¯10-6). However, compared to nonepileptic controls FSe was associated with both CVD (pâ¯<â¯0.0019) and stroke (pâ¯<â¯6.62â¯×â¯10-10). Functional stroke was significantly more common in patients with FSe (39.13%) than patients with ES (4.12%) (pâ¯=â¯4.47â¯×â¯10-9). Compared to patients with ES, patients with FSe were younger (pâ¯=â¯0.00022), more likely to be female (pâ¯=â¯0.00040), and more likely to have comorbid mental health needs including anxiety (pâ¯=â¯1.06â¯×â¯10-6), PTSD or history of trauma (e.g., sexual abuse) (pâ¯=â¯1.06â¯×â¯10-13), and bipolar disorder (pâ¯=â¯0.0011). CONCLUSION: Our results confirm the initial observation of increased CVD in patients with FSe and further suggest that patients with FSe may be predisposed to developing another functional neurological disorder (FND) (i.e., functional stroke). We speculate that this may be due to shared risk factors and pathophysiological processes that are common to various manifestations of FND.
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Transtornos Cerebrovasculares , Acidente Vascular Cerebral , Estudos de Casos e Controles , Transtornos Cerebrovasculares/complicações , Transtornos Cerebrovasculares/epidemiologia , Eletroencefalografia/métodos , Feminino , Humanos , Masculino , Estudos Retrospectivos , Convulsões/complicações , Convulsões/epidemiologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/epidemiologiaRESUMO
PURPOSE: The percentage of a maternal cell-free DNA (cfDNA) sample that is fetal-derived (the fetal fraction; FF) is a key driver of the sensitivity and specificity of noninvasive prenatal screening (NIPS). On certain NIPS platforms, >20% of women with high body mass index (and >5% overall) receive a test failure due to low FF (<4%). METHODS: A scalable fetal fraction amplification (FFA) technology was analytically validated on 1264 samples undergoing whole-genome sequencing (WGS)-based NIPS. All samples were tested with and without FFA. RESULTS: Zero samples had FF < 4% when screened with FFA, whereas 1 in 25 of these same patients had FF < 4% without FFA. The average increase in FF was 3.9-fold for samples with low FF (2.3-fold overall) and 99.8% had higher FF with FFA. For all abnormalities screened on NIPS, z-scores increased 2.2-fold on average in positive samples and remained unchanged in negative samples, powering an increase in NIPS sensitivity and specificity. CONCLUSION: FFA transforms low-FF samples into high-FF samples. By combining FFA with WGS-based NIPS, a single round of NIPS can provide nearly all women with confident results about the broad range of potential fetal chromosomal abnormalities across the genome.
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Ácidos Nucleicos Livres , Teste Pré-Natal não Invasivo , Aneuploidia , Ácidos Nucleicos Livres/genética , Aberrações Cromossômicas , Feminino , Feto , Humanos , Gravidez , Cuidado Pré-Natal , Diagnóstico Pré-NatalRESUMO
OBJECTIVE: Depression and anxiety disorders are common among patients with epilepsy (PWE). These comorbidities have been shown to influence prognosis and may have a greater impact on quality of life than seizure control. Despite guideline recommendations and expert consensus to regularly screen for and treat both conditions, there is evidence that they are underdiagnosed and undertreated. Our goal was to test a novel screening method to determine if it would increase the rate of detecting and treating depression and anxiety disorders among PWE. METHOD: The Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) and the Brief Epilepsy Anxiety Survey Instrument (brEASI) were selected as validated screening instruments for depression and anxiety disorders, respectively. They were sent via an electronic medical record-linked patient portal to all patients of four epileptologists 48â¯h prior to their clinic appointment. We evaluated whether this increased the rate of detecting and treating depression and anxiety disorders relative to a historical control group. RESULTS: A total of 563 patients were included of whom 351 were sent the screening instruments. 62.7% of patients completed the screening instruments of whom 47.7% screened positive for either depression only (16.4%), anxiety disorders only (5.5%) or both (25.9%); a statistically significant increase relative to the control group. There was also a significantly increased proportion of patients for whom treatment was initiated for depression (pâ¯<â¯0.01), anxiety disorders (pâ¯<â¯0.01), or both (pâ¯<â¯0.01). CONCLUSIONS: We identified an easily applicable and efficient means of enhancing detection and treatment rates for depression and anxiety disorders among PWE in a busy clinic setting.
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Depressão , Epilepsia , Adulto , Ansiedade/diagnóstico , Ansiedade/epidemiologia , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/terapia , Depressão/diagnóstico , Depressão/epidemiologia , Registros Eletrônicos de Saúde , Epilepsia/complicações , Epilepsia/diagnóstico , Epilepsia/epidemiologia , Humanos , Escalas de Graduação Psiquiátrica , Qualidade de Vida , Reprodutibilidade dos TestesRESUMO
While temporal lobe epilepsy (TLE) is a focal epilepsy, previous work demonstrates that TLE causes widespread brain-network disruptions. Impaired visuospatial attention and learning in TLE may be related to thalamic arousal nuclei connectivity. Our prior preliminary work in a smaller patient cohort suggests that patients with TLE demonstrate abnormal functional connectivity between central lateral (CL) thalamic nucleus and medial occipital lobe. Others have shown pulvinar connectivity disturbances in TLE, but it is incompletely understood how TLE affects pulvinar subnuclei. Also, the effects of epilepsy surgery on thalamic functional connectivity remains poorly understood. In this study, we examine the effects of TLE on functional connectivity of two key thalamic arousal-nuclei: lateral pulvinar (PuL) and CL. We evaluate resting-state functional connectivity of the PuL and CL in 40 patients with TLE and 40 controls using fMRI. In 25 patients, postoperative images (>1 year) were also compared with preoperative images. Compared to controls, patients with TLE exhibit loss of normal positive connectivity between PuL and lateral occipital lobe (pâ¯<â¯0.05), and a loss of normal negative connectivity between CL and medial occipital lobe (pâ¯<â¯0.01, paired t-tests). FMRI amplitude of low-frequency fluctuation (ALFF) in TLE trended higher in ipsilateral PuL (pâ¯=â¯0.06), but was lower in the lateral occipital (pâ¯<â¯0.01) and medial occipital lobe in patients versus controls (pâ¯<â¯0.05, paired t-tests). More abnormal ALFF in the ipsilateral lateral occipital lobe is associated with worse preoperative performance on Rey Complex Figure Test Immediate (pâ¯<â¯0.05, râ¯=â¯0.381) and Delayed scores (pâ¯<â¯0.05, râ¯=â¯0.413, Pearson's Correlations). After surgery, connectivity between PuL and lateral occipital lobe remains abnormal in patients (pâ¯<â¯0.01), but connectivity between CL and medial occipital lobe improves and is no longer different from control values (pâ¯>â¯0.05, ANOVA, post hoc Fischer's LSD). In conclusion, thalamic arousal nuclei exhibit abnormal connectivity with occipital lobe in TLE, and some connections may improve after surgery. Studying thalamic arousal centers may help explain distal network disturbances in TLE.
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Epilepsia do Lobo Temporal , Nível de Alerta , Encéfalo , Epilepsia do Lobo Temporal/complicações , Epilepsia do Lobo Temporal/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Tálamo/diagnóstico por imagemRESUMO
OBJECTIVE: In patients with medically refractory focal epilepsy, stereotactic-electroencephalography (SEEG) can aid in localizing epileptogenic regions for surgical treatment. SEEG, however, requires long hospitalizations to record seizures, and ictal interpretation can be incomplete or inaccurate. Our recent work showed that non-directed resting-state analyses may identify brain regions as epileptogenic or uninvolved. Our present objective is to map epileptogenic networks in greater detail and more accurately identify seizure-onset regions using directed resting-state SEEG connectivity. METHODS: In 25 patients with focal epilepsy who underwent SEEG, 2 minutes of resting-state, artifact-free, SEEG data were selected and functional connectivity was estimated. Using standard clinical interpretation, brain regions were classified into four categories: ictogenic, early propagation, irritative, or uninvolved. Three non-directed connectivity measures (mutual information [MI] strength, and imaginary coherence between and within regions) and four directed measures (partial directed coherence [PDC] and directed transfer function [DTF], inward and outward strength) were calculated. Logistic regression was used to generate a predictive model of ictogenicity. RESULTS: Ictogenic regions had the highest and uninvolved regions had the lowest MI strength. Although both PDC and DTF inward strengths were highest in ictogenic regions, outward strengths did not differ among categories. A model incorporating directed and nondirected connectivity measures demonstrated an area under the receiver-operating characteristic (ROC) curve (AUC) of 0.88 in predicting ictogenicity of individual regions. The AUC of this model was 0.93 when restricted to patients with favorable postsurgical seizure outcomes. SIGNIFICANCE: Directed connectivity measures may help identify epileptogenic networks without requiring ictal recordings. Greater inward but not outward connectivity in ictogenic regions at rest may represent broad inhibitory input to prevent seizure generation.
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Encéfalo/fisiopatologia , Eletroencefalografia/métodos , Epilepsias Parciais/fisiopatologia , Rede Nervosa/fisiopatologia , Descanso , Técnicas Estereotáxicas , Adulto , Encéfalo/diagnóstico por imagem , Epilepsias Parciais/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Adulto JovemRESUMO
BACKGROUND: Automatisms are frequently encountered during video-monitoring of patients with focal epilepsy in the EMU and generally thought to have a low lateralizing value in isolation. Rhythmic ictal nonclonic hand (RINCH) motions have been described in small series as a potentially lateralizing semiologic sign. We aimed to expand on prior work and determine the prevalence, characteristics, and lateralizing value of RINCH motions in general epilepsy monitoring unit (EMU) population with focal epilepsy. METHODS: All patients with recorded seizures in the EMU were included in our database search. Search was performed to identify seizures with reported RINCH motions. Both electroencephalography (EEG) and video of identified seizures were reviewed. RESULTS: We identified RINCH motions in 131 seizures in 71 patients. Overall seizure localization was temporal in 57 patients, frontotemporal in 3 patients, and extratemporal in 7 patients. We estimated RINCH motions to occur in 8.5% of EMU patients with recorded seizures. The most common RINCH motions in descending order were as follows: hand opening and closing, finger rubbing, milking motions, finger flexion/extension, and pill rolling. The mean RINCH motion latency from seizure onset was 34.48â¯s in temporal lobe epilepsy and 10.31â¯s in frontal lobe epilepsy. The RINCH motions were contralateral to seizure onset in 61 of 65 (93.8%) with lateralized seizure onset. Dystonic posturing was present in 43% of seizures with RINCH motions. CONCLUSION: The RINCH motions are a common sign in focal seizures and should be distinguished from other types of manual automatism as they carry a strong lateralizing value.
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Automatismo/diagnóstico , Eletroencefalografia , Epilepsias Parciais/fisiopatologia , Lateralidade Funcional , Mãos/fisiopatologia , Convulsões/diagnóstico , Adulto , Automatismo/etiologia , Automatismo/fisiopatologia , Criança , Epilepsias Parciais/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , Convulsões/etiologia , Convulsões/fisiopatologia , Gravação em VídeoRESUMO
How to cite this article: Tiwari NR, Chaudhari KS, Sharma R, Haas KP, Sharma VR. Antiplatelet Agents in Sepsis-Putting it all together: A Call to Action. Indian J Crit Care Med 2020;24(6):483-484.
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BACKGROUND: By identifying pathogenic variants across hundreds of genes, expanded carrier screening (ECS) enables prospective parents to assess the risk of transmitting an autosomal recessive or X-linked condition. Detection of at-risk couples depends on the number of conditions tested, the prevalence of the respective diseases, and the screen's analytical sensitivity for identifying disease-causing variants. Disease-level analytical sensitivity is often <100% in ECS tests because copy number variants (CNVs) are typically not interrogated because of their technical complexity. METHODS: We present an analytical validation and preliminary clinical characterization of a 235-gene sequencing-based ECS with full coverage across coding regions, targeted assessment of pathogenic noncoding variants, panel-wide CNV calling, and specialized assays for technically challenging genes. Next-generation sequencing, customized bioinformatics, and expert manual call review were used to identify single-nucleotide variants, short insertions and deletions, and CNVs for all genes except FMR1 and those whose low disease incidence or high technical complexity precluded novel variant identification or interpretation. RESULTS: Screening of 36859 patients' blood or saliva samples revealed the substantial impact on fetal disease-risk detection attributable to novel CNVs (9.19% of risk) and technically challenging conditions (20.2% of risk), such as congenital adrenal hyperplasia. Of the 7498 couples screened, 335 were identified as at risk for an affected pregnancy, underscoring the clinical importance of the test. Validation of our ECS demonstrated >99% analytical sensitivity and >99% analytical specificity. CONCLUSIONS: Validated high-fidelity identification of different variant types-especially for diseases with complicated molecular genetics-maximizes at-risk couple detection.
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Variações do Número de Cópias de DNA , Éxons , Triagem de Portadores Genéticos , Estudos de Coortes , Humanos , Mutação INDEL , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Treatment for Angelman syndrome (AS) is currently limited to symptomatic interventions. A mouse model of AS has reduced calcium/calmodulin-dependent kinase II activity due to excessive phosphorylation of specific threonine residues, leading to diminished long-term potentiation. In a rat model of Parkinson disease, levodopa reduced phosphorylation of various proteins, including calcium/calmodulin-dependent kinase II. Further studies demonstrated that AS mice treated with levodopa performed better on rotarod testing than untreated AS mice. We conducted a multi-center double-blind randomized placebo-controlled 1-year trial of levodopa / carbidopa with either 10 or 15 mg/kg/day of levodopa in children with AS. The outcome of this intervention was assessed using either the Bayley Scales of Infant Development or the Mullen Scales of Early Learning, as well as the Vineland Adaptive Behavior Scales, and the Aberrant Behavior Checklist. Of the 78 participants enrolled, 67 participants received study medication (33 on levodopa, 34 on placebo), and 55 participants (29 on levodopa, 26 on placebo) completed the 1-year study. There were no clinically or statistically significant changes in any of the outcome measures over a 1-year period comparing the levodopa and placebo groups. The number of adverse events reported, including the more serious adverse events, was similar in both groups, but none were related to treatment with levodopa. Our data demonstrate that levodopa is well-tolerated by children with AS. However, in the doses used in this study, it failed to improve their neurodevelopment or behavioral outcome.
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Síndrome de Angelman/tratamento farmacológico , Levodopa/uso terapêutico , Síndrome de Angelman/diagnóstico , Síndrome de Angelman/fisiopatologia , Síndrome de Angelman/psicologia , Animais , Biomarcadores , Cálcio/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Modelos Animais de Doenças , Humanos , Levodopa/administração & dosagem , Potenciação de Longa Duração , Camundongos , Testes Neuropsicológicos , Resultado do TratamentoRESUMO
BACKGROUND: Lung cancer screening can reduce mortality but can be a complex, multi-step process. Poor health literacy is associated with unfavorable outcomes and decreased use of preventative services, so it is important to address barriers to care through efficient and practical education. The readability of lung cancer screening materials for patients is unknown and may not be at the recommended 6th grade reading level set by the American Medical Association. Our goals were to: (1) measure the health literacy of a lung cancer screening population from an urban academic medical center, and (2) examine the readability of online educational materials for lung cancer screening. METHODS: We performed a retrospective cross sectional study at a single urban academic center. Health literacy was assessed using three validated screening questions. To assess the readability of educational materials, we performed a Google search using the phrase, "What is lung cancer screening?" and the Flesch-Kincaid Grade Level (FKGL) formula was used to estimate the grade level required to understand the text. RESULTS: There were 404 patients who underwent lung cancer screening during the study period. The prevalence of inadequate/marginal health literacy was 26.7-38.0%. Fifty websites were reviewed and four were excluded from analysis because they were intended for medical providers. The mean FKGL for the 46 websites combined was 10.6 ± 2.2. CONCLUSIONS: Low health literacy was common and is likely a barrier to appropriate education for lung cancer screening. The current online educational materials regarding lung cancer screening are written above the recommended reading level set by the American Medical Association.
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Compreensão , Detecção Precoce de Câncer , Educação a Distância , Letramento em Saúde/estatística & dados numéricos , Neoplasias Pulmonares/diagnóstico , Educação de Pacientes como Assunto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estados UnidosRESUMO
PURPOSE OF REVIEW: Hepatic hydrothorax is a complication of end-stage liver disease that may have significant associated morbidity. Sodium restriction and diuretic therapy are the mainstays of treatment, though up to a quarter of patients will become refractory to this and will require a pleural drainage procedure. Thoracentesis, transjugular intrahepatic portosystemic shunt, and chemical pleurodesis all have variable success rates and associated complications in the management of hepatic hydrothorax. Indwelling tunneled pleural catheters (ITPC) have been successfully used to manage recurrent symptomatic malignant pleural effusions, and there is growing interest regarding their use in the management of hepatic hydrothorax. RECENT FINDINGS: Evidence regarding the use of ITPC for nonmalignant pleural effusions has been limited to retrospective studies and small feasibility trials. A recent meta-analysis regarding the use of IPTC for nonmalignant pleural effusions demonstrated a rate of spontaneous pleurodesis of 51%, whereas a small, prospective study demonstrated spontaneous pleurodesis rates of 33% and an infection rate of 16.7% in 24 patients with ITPC placed for hepatic hydrothorax in patients suitable for liver transplant evaluation. SUMMARY: ITPC may be an acceptable treatment option for the management of hepatic hydrothorax which are refractory to conventional medical management. Larger, randomized controlled trials are needed to further evaluate the safety and efficacy of these catheters for the management of nonmalignant pleural effusions.
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Hidrotórax , Falência Renal Crônica/complicações , Toracentese , Gerenciamento Clínico , Humanos , Hidrotórax/diagnóstico , Hidrotórax/etiologia , Hidrotórax/terapia , Toracentese/instrumentação , Toracentese/métodosRESUMO
RATIONALE: Epilepsy and psychogenic nonepileptic spells (PNES) can coexist, often posing diagnostic and therapeutic challenges. We sought to identify clinical and historical characteristics of two groups of patients, those with coexisting epilepsy and PNES and those with PNES alone, and determine the prevalence of coexisting epilepsy/PNES with strict diagnostic criteria in a large group of epilepsy monitoring unit (EMU) patients. METHODS: We reviewed the medical records of all consecutive patients admitted to the Vanderbilt University Medical Center Adult EMU between July 1, 2007 and June 30, 2012. We identified patients with recorded PNES and classified them as having coexisting epilepsy/PNES or PNES alone and then systematically compared the clinical characteristics of these two groups. RESULTS: A total of 1567 patient medical records were reviewed. The prevalence rate of coexisting epilepsy/PNES was 5.2% among all EMU admissions (12.3% of all patients with epilepsy and 14.8% of all patients with PNES). These rates were lower when patients with interictal epileptiform activity (IEA) alone and no recorded ictal discharges were not included in the group with epilepsy (2.6%, 6.2%, and 7.4%, respectively). The accuracy of pre-EMU clinical suspicion was significantly higher in the group with PNES-only. Patients with epilepsy/PNES were significantly more likely to require more than one EMU admission for definitive diagnosis. The first PNES event preceded an epileptic seizure (ES) in 94.4% of patients with epilepsy/PNES. The group with PNES-only had significantly higher suggestibility, and the group with epilepsy/PNES had a significantly higher presence of epilepsy risk factors. Abnormal neurological examination and abnormal brain MRI were also significantly more common in the group with epilepsy/PNES. CONCLUSIONS: Our study defined the prevalence of coexisting epilepsy/PNES in a large cohort with strict diagnostic criteria and outlined specific clinical and historical characteristics differentiating the two groups of patients with coexisting epilepsy/PNES and PNES-only. These findings should help guide clinicians to reach the correct diagnosis faster and provide appropriate treatment earlier.
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Encéfalo/fisiopatologia , Eletroencefalografia/métodos , Epilepsia/diagnóstico , Transtornos Psicofisiológicos/diagnóstico , Convulsões/diagnóstico , Adulto , Epilepsia/fisiopatologia , Epilepsia/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Psicofisiológicos/fisiopatologia , Transtornos Psicofisiológicos/psicologia , Convulsões/fisiopatologia , Convulsões/psicologiaRESUMO
In 2011, the American Academy of Neurology (AAN) established eight epilepsy quality measures (EQMs) for chronic epilepsy treatment to address deficits in quality of care. This study assesses the relationship between adherence to these EQMs and epilepsy-related adverse hospitalizations (ERAHs). A retrospective chart review of 475 new epilepsy clinic patients with an ICD-9 code 345.1-9 between 2010 and 2012 was conducted. Patient demographics, adherence to AAN guidelines, and annual number of ERAHs were assessed. Fisher's exact test was used to assess the relationship between adherence to guidelines (as well as socioeconomic variables) and the presence of one or more ERAH per year. Of the eight measures, only documentation of seizure frequency, but not seizure type, correlated with ERAH (relative risk [RR] 0.343, 95% confidence interval [CI] 0.176-0.673, p = 0.010). Among patients in the intellectually disabled population (n = 70), only review/request of neuroimaging correlated with ERAH (RR 0.128, 95% CI 0.016-1.009, p = 0.004). ERAHs were more likely in African American patients (RR 2.451, 95% CI 1.377-4.348, p = 0.008), Hispanic/Latino patients (RR 4.016, 95% CI 1.721-9.346, p = 0.016), Medicaid patients (RR 2.217, 95% CI 1.258-3.712, p = 0.009), and uninsured patients (RR 2.667, 95% CI 1.332-5.348, p = 0.013). In this retrospective series, adherence to the eight AAN quality measures did not strongly correlate with annual ERAH.
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Epilepsia/diagnóstico , Epilepsia/psicologia , Fidelidade a Diretrizes/normas , Hospitalização/estatística & dados numéricos , Neurologia/normas , Adulto , Epilepsia/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Non-convulsive seizures (NCS) or non-convulsive status epilepticus (NCSE) has been reported in 8-20 % of critically ill patient populations, and delayed diagnosis and treatment of NCSE may lead to increased mortality. This study seeks to better understand the risk factors, characteristics, and outcome of NCS/NCSE in the neurological ICU. METHODS: This is a prospective observational study, recruiting consecutive patients admitted to the adult neurological ICU with altered mental status. Patients with anoxic brain injury were excluded from the study. Data were collected and analyzed for prevalence of NCSE/NCS, EEG patterns, associated risk factors, treatment response, and final outcome. RESULTS: NCSE/NCS was detected in 21 % of 170 subjects. Clinical seizures preceded EEG diagnosis of NCSE/NCS in 25 % of cases. Significant risk factors for NCSE/NCS were a past medical history of intracranial tumor, epilepsy, or meningitis/encephalitis, or MRI evidence of encephalomalacia. Subtle clinical findings such as twitching of oral or ocular muscles and eye deviations were found on exam in 50 % of the NCSE/NCS group. Mortality was increased in NCSE cases as 31 % of NCSE/NCS patients died compared to 14 % in non-NCSE/NCS group. CONCLUSIONS: Specific clinical features along with history and imaging findings may be used to identify patients at high risk of NCSE/NCS in the neurological ICU.
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Unidades de Terapia Intensiva/estatística & dados numéricos , Convulsões/diagnóstico , Convulsões/epidemiologia , Estado Epiléptico/diagnóstico , Estado Epiléptico/epidemiologia , Adulto , Idoso , Eletroencefalografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
OBJECTIVE: To determine the feasibility of administering a diazepam nasal spray formulation (diazepam-NS) to adults with epilepsy during a generalized tonic-clonic seizure or in the postictal period following a tonic-clonic or other seizure type, to assess pharmacokinetics and to assess tolerability. METHODS: An open-label study was conducted in patients admitted to the epilepsy monitoring unit. Eligible patients received a single dose of diazepam-NS approximating 0.2 mg/kg. Plasma diazepam concentrations were measured serially up to 12 h postdose, and maximum observed plasma concentration (Cmax ); time to maximum concentration (Tmax ); and the area under the plasma concentration-time curve for time zero to last sampling time (AUC0-12 ) were estimated and dose-normalized. Pharmacodynamic assessments included Kaplan-Meier analysis to determine the time-to-next seizure. Safety and tolerability were assessed. RESULTS: Of the 78 patients who consented, 30 had treatment and pharmacokinetic data. Ten patients were treated during a convulsive tonic-clonic seizure, seven within 5 min following the last clonic jerk, and 13 in the postictal period ≥ 5 min after a tonic-clonic or following other seizure-types. Diazepam median Tmax was 45 min. Dose-normalized mean Cmax and AUC0-12 values of diazepam were comparable among patients regardless of the timing of diazepam-NS administration in relation to seizure. Of those treated, 65% were seizure-free during the 12-h observation period and 35% had post-dose seizures. Treatment was well tolerated, with no unexpected safety findings: 74% had mild and 25% had moderate adverse events. Nasopharyngeal signs were resolved by 12 h postdose. SIGNIFICANCE: Diazepam can be delivered in effective therapeutic concentrations by a nasal spray device during the convulsive phase of tonic-clonic seizures or in the postictal periods following tonic-clonic or other seizure types.
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Anticonvulsivantes/uso terapêutico , Diazepam/uso terapêutico , Epilepsia Tônico-Clônica/tratamento farmacológico , Administração Intranasal , Adolescente , Adulto , Idoso , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/sangue , Anticonvulsivantes/farmacocinética , Diazepam/administração & dosagem , Diazepam/efeitos adversos , Diazepam/sangue , Diazepam/farmacocinética , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
Background: Radial probe endobronchial ultrasound (R-EBUS) is often utilized in guided bronchoscopy for the diagnosis of peripheral pulmonary lesions. R-EBUS probe positioning has been shown to correlate with diagnostic yield, but overall diagnostic yield with this technology has been inconsistent across the published literature. Currently there is no standardization for R-EBUS image interpretation, which may result in variability in grading concentricity of lesions and subsequently procedure performance. This was a survey-based study evaluating variability among practicing pulmonologists in R-EBUS image interpretation. Methods: R-EBUS images from peripheral bronchoscopy cases were sent to 10 practicing Interventional Pulmonologists at two different time points (baseline and 3 months). Participants were asked to grade the images as concentric, eccentric, or no image. Cohen's Kappa-coefficient was calculated for inter- and intra-observer variability. Results: A total of 100 R-EBUS images were included in the survey. There was 100% participation with complete survey responses from all 10 participants. Overall kappa-statistic for inter-observer variability for Survey 1 and 2 was 0.496 and 0.477 respectively. Overall kappa-statistic for intra-observer variability between the two surveys was 0.803. Conclusions: There is significant variability between pulmonologists when characterizing R-EBUS images. However, there is strong intra-rater agreement from each participant between surveys. A standardized approach and grading system for radial EBUS patterns may improve inter-observer variability in order to optimize our clinical use and research efforts in the field.
RESUMO
BACKGROUND: Epilepsy is a common neurological disorder that affects approximately 50 million people worldwide. Both risk of epilepsy and response to treatment partly depend on genetic factors, and gene identification is a promising approach to target new prediction, treatment, and prevention strategies. However, despite significant progress in the identification of genes causing epilepsy in families with a Mendelian inheritance pattern, there is relatively little known about the genetic factors responsible for common forms of epilepsy and so-called epileptic encephalopathies. Study design The Epilepsy Phenome/Genome Project (EPGP) is a multi-institutional, retrospective phenotype-genotype study designed to gather and analyze detailed phenotypic information and DNA samples on 5250 participants, including probands with specific forms of epilepsy and, in a subset, parents of probands who do not have epilepsy. RESULTS: EPGP is being executed in four phases: study initiation, pilot, study expansion/establishment, and close-out. This article discusses a number of key challenges and solutions encountered during the first three phases of the project, including those related to (1) study initiation and management, (2) recruitment and phenotyping, and (3) data validation. The study has now enrolled 4223 participants. CONCLUSIONS: EPGP has demonstrated the value of organizing a large network into cores with specific roles, managed by a strong Administrative Core that utilizes frequent communication and a collaborative model with tools such as study timelines and performance-payment models. The study also highlights the critical importance of an effective informatics system, highly structured recruitment methods, and expert data review.
Assuntos
Epilepsia/genética , Genótipo , Fenótipo , Pesquisa em Genética , Humanos , Gestão da Informação , Análise de Sequência com Séries de Oligonucleotídeos , Projetos de Pesquisa , Estudos RetrospectivosRESUMO
The evaluation of the Fisher information matrix for the probability density of trajectories generated by the over-damped Langevin dynamics at equilibrium is presented. The framework we developed is general and applicable to any arbitrary potential of mean force where the parameter set is now the full space dependent function. Leveraging an innovative Hermitian form of the corresponding Fokker-Planck equation allows for an eigenbasis decomposition of the time propagation probability density. This formulation motivates the use of the square root of the equilibrium probability density as the basis for evaluating the Fisher information of trajectories with the essential advantage that the Fisher information matrix in the specified parameter space is constant. This outcome greatly eases the calculation of information content in the parameter space via a line integral. In the continuum limit, a simple analytical form can be derived to explicitly reveal the physical origin of the information content in equilibrium trajectories. This methodology also allows deduction of least informative dynamics models from known or available observables that are either dynamical or static in nature. The minimum information optimization of dynamics is performed for a set of different constraints to illustrate the generality of the proposed methodology.