First seizure in elderly patients: Need to treat? Evidence from a retrospective study.

BACKGROUND: The risk of seizure recurrence after a first unprovoked epileptic seizure is reported to be approximately 40%. Little is known about the recurrence risk after a first seizure in elderly patients, who may be at higher risk due to an increased rate of structural lesions, encephalopathy, subcortical arteriosclerotic encephalopathy or brain atrophy. METHODS: In a retrospective approach, the recurrence rate in 304 patients aged 60 years and above who presented with a first seizure between 2004 and 2017 was analyzed. Hierarchical Cox regression was used to investigate the impact of EEG and neuroimaging results, age or the prescription of anti-seizure medication (ASM) on seizure recurrence. RESULTS: Seizure recurrence rates were 24.5% and 34.4% after one and two years, respectively. Anti-seizure medication was started in 87.8% of patients, in 28.8% despite the absence of clear epileptogenic lesions on neuroimaging or epileptiform potentials in the EEG. Medical treatment significantly reduced the risk of recurrence (hazard ratio = 0.47). Epileptiform potentials in the EEG, epileptogenic lesions in neuroimaging and age had no significant effect on seizure recurrence. Age and the presence of neurodegenerative and psychiatric comorbidities showed a significant association with ASM prescription. CONCLUSIONS: The present data show a strong protective effect of ASM on seizure recurrence in patients above the age of 60, even in the absence of pathologic neuroimaging or EEG results needed for the diagnosis of epilepsy. Treatment with ASM therefore seems beneficial for reducing the recurrence risk in elderly patients. The lack of a significant association between seizure recurrence and epileptogenic lesions might be related to other confounding factors like encephalopathy, subcortical arteriosclerotic encephalopathy, neurodegenerative diseases or brain atrophy.

First epileptic seizure and quality of life - A prospective study.

OBJECTIVE: Impaired QoL and depression are common in patients with chronic epilepsies; however, data on the impact of a first seizure on QoL are sparse. According to the current ILAE-definition of epilepsy, patients may be diagnosed with epilepsy immediately after the first seizure, if EEG and/or imaging findings are abnormal. Patients with normal findings in imaging and EEG are not diagnosed as having epilepsy. We investigated QoL in patients after a first seizure with and without a consecutive diagnosis of epilepsy to detect differences between groups within the first year after seizure. METHODS: We examined patients (n = 152) after a first epileptic seizure and six and 12 months thereafter using demographic, clinical and QoL-related questionnaire data (Short Form-36 Health Survey (SF-36), Quality of Life in Epilepsy Inventory-31 (QOLIE-31), Beck's depression inventory II (BDI-II)). RESULTS: Patients diagnosed with epilepsy after the first seizure showed a tendency of reduced mental health-related QoL six (p =.098) and 12 months (p =.092) after the first seizure compared to patients who were not diagnosed with epilepsy, but were diagnosed as having had a single first seizure. There were no significant differences between the two groups in physical health-related QoL. Multiple regression analyses showed that especially depressive symptoms explained 22.0 - 48.7 % of the variance in mental health-related QoL six (p <.001) and 12 months (p <.001) after the first seizure. Physical health-related QoL was especially predicted by age (p <.001), group (p =.002) and recurrent seizures (p = < 0.001). In PWE, there was a statistical trend with improving QOLIE-31 overall scores from six to 12 months (p =.086). CONCLUSION: Our results suggest that QoL may be impaired in patients diagnosed with epilepsy early, immediately after the onset of disease. Early follow-up monitoring from the beginning of patient career is important for possible interventions and to improve patients' daily life in the long term.

Effect of transcutaneous vagus nerve stimulation on stress-reactive neuroendocrine measures in a sample of persons with temporal lobe epilepsy.

OBJECTIVE: Dysregulation of stress-reactive neuroendocrine measures, as well as subjective stress, have been found to worsen epilepsy. Transcutaneous vagus nerve stimulation (tVNS) is a relatively new treatment option for epilepsy. We were interested in its effect on the activity of the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS) as well as subjective stress and tiredness in patients with temporal lobe epilepsy (TLE). METHODS: Twenty patients (age 44 ± 11 years, 13 women) were enrolled in the study. They were free of seizures for more than 1 year. All took part in two sessions with 4 h of stimulation (tVNS vs. sham) in a randomized order. Saliva samples and subjective stress and tiredness levels were measured at five time points each session (before and after stimulation and three time points every hour in between). Data were analyzed using repeated measures analysis of variance as well as paired t-tests. RESULTS: There was a dampened salivary cortisol (sCort) decrease during tVNS (time × condition effect: F[2.38, 38.15] = 6.50, P = 0.002, partial η2 = 0.29). Furthermore, we detected a dampened increase in salivary flow rate during tVNS (time × condition effect: F[3.28, 55.67] = 2.82, P = 0.043, partial η2 = 0.14). There was neither a difference in overall sCort or salivary alpha-amylase (sAA) levels nor in subjective stress or tiredness levels between conditions. sAA levels at the last measurement point were slightly higher during tVNS (t(19) = 2.26, P = 0.035, d = 0.51), but this effect failed to reach significance when controlled for multiple comparisons. SIGNIFICANCE: Our results partially support that tVNS influences the regulation of stress-reactive neuroendocrine systems (namely the HPA axis and ANS) in epilepsy. More research with larger samples is needed on the difference between short-term and repeated long-term stimulation.

Effect of the revised definition of epilepsy on treatment decisions and seizure recurrence after a first epileptic seizure.

BACKGROUND: Studies on risk factors for epilepsy and seizure recurrence after a first seizure are usually based on the old definition of epilepsy with the need for two unprovoked seizures. The current definition of epilepsy allows diagnosis and treatment of epilepsy after a first seizure if the recurrence risk is >60%. We evaluate treatment decisions, seizure recurrence and risk factors for epilepsy related to the application of the new definition of epilepsy. METHODS: Data of 629 patients with a first seizure were analyzed to investigate changes of treatment decisions and seizure recurrence after the revised definition of epilepsy. We used binary logistic regression to investigate the impact of multiple factors influencing seizure recurrence like electroencephalogram (EEG) and magnetic resonance imaging (MRI) results and administration of antiseizure medication (ASM). RESULTS: The proportion of patients receiving ASM significantly increased from 70.4% to 80.5% (p = 0.015) following the new epilepsy definition, without any significant changes in the recurrence rate (40.8% vs. 45.5% after 2 years, p > 0.05). The presence of interictal epileptiform discharges (IED) in the EEG increased (OR = 1.98) and administration of ASM decreased (OR = 0.43) recurrence rates significantly. CONCLUSIONS: The new definition of epilepsy was associated with increased application of ASM, but not with reduced recurrence rates. The study confirms the presence of IED as a strong risk factor for seizure recurrence and the protective effect of ASM. The influence of imaging findings, which have a strong impact on the new definition of epilepsy, could not be confirmed.

Non-invasive vagus nerve stimulation in epilepsy patients enhances cooperative behavior in the prisoner's dilemma task.

The vagus nerve constitutes a key link between the autonomic and the central nervous system. Previous studies provide evidence for the impact of vagal activity on distinct cognitive processes including functions related to social cognition. Recent studies in animals and humans show that vagus nerve stimulation is associated with enhanced reward-seeking and dopamine-release in the brain. Social interaction recruits similar brain circuits to reward processing. We hypothesize that vagus nerve stimulation (VNS) boosts rewarding aspects of social behavior and compare the impact of transcutaneous VNS (tVNS) and sham stimulation on social interaction in 19 epilepsy patients in a double-blind pseudo-randomized study with cross-over design. Using a well-established paradigm, i.e., the prisoner's dilemma, we investigate effects of stimulation on cooperative behavior, as well as interactions of stimulation effects with patient characteristics. A repeated-measures ANOVA and a linear mixed-effects model provide converging evidence that tVNS boosts cooperation. Post-hoc correlations reveal that this effect varies as a function of neuroticism, a personality trait linked to the dopaminergic system. Behavioral modeling indicates that tVNS induces a behavioral starting bias towards cooperation, which is independent of the decision process. This study provides evidence for the causal influence of vagus nerve activity on social interaction.

Perception of memory performance after first seizure in patients with and without an epilepsy diagnosis.

OBJECTIVES: Memory complaints in patients with epilepsy have been well-studied. Although memory complaints are commonly reported by patients with chronic epilepsy, to date, few studies exist on memory complaints at the onset of epilepsy. The present study investigated the presence of memory complaints and their relation to mood and memory performance in patients after their first seizure. Thereby, we examined differences between individuals who received a diagnosis of epilepsy immediately with the occurrence of their first seizure and those who were diagnosed as having the first epileptic seizure, without fulfilling the ILAE criteria for the diagnosis of epilepsy. METHODS: Sixty-one patients participated in the study and completed, among others, a memory task and questionnaires on memory complaints and depression after their first epileptic seizure. We investigated the level of memory complaints and their correlation and accuracy in classification with a memory measure. We compared patients who received an epilepsy diagnosis after the first seizure with those who did not. RESULTS: Memory complaints did not correlate with objective memory performance. Classification into impaired/unimpaired showed low concordance between memory complaints and neuropsychological memory measures. After their first epileptic seizure, patients reported few memory complaints overall (10%), and there were no differences in memory complaints between patients with and without an epilepsy diagnosis. CONCLUSION: At epilepsy onset, in contrast to established epilepsies, memory complaints are rare. Although influences of anticonvulsant drugs and seizures are not present at the beginning of epilepsy, this substantial absence of memory complaints at epilepsy onset emphasizes the need for comprehensive neurological and psychological treatment early with the given diagnosis. Treatment should focus on anticonvulsant drug regimens, patients' concerns and convey realistic expectations.

Transcutaneous auricular vagus nerve stimulation influences gastric motility: A randomized, double-blind trial in healthy individuals.

BACKGROUND: Transcutaneous auricular vagus nerve stimulation (taVNS) has been investigated regarding its therapeutic properties in several several conditions such as epilepsy, migraine and major depressive disorder and was shown to access similar neural pathways as invasive vagus nerve stimulation. While the vagus nerve's role in gut motility is physiologically established, the effect of taVNS has scarcely been investigated in humans and yielded conflicting results. Real-time gastric magnetic resonance imaging (rtMRI) is an established reproducible method to investigate gastric motility non-invasively. OBJECTIVE: To investigate the influence of taVNS on gastric motility of healthy participants using rtMRI. METHODS: We conducted a randomized, double-blind study using high-frequency (HF) stimulation at 25Hz or low-frequency (LF) taVNS at 1Hz after ingestions of a standardized meal in 57 healthy participants. The gastric motility index (GMI) was determined by measuring the amplitude and velocity of the peristaltic waves using rtMRI. RESULTS: After HF taVNS, GMI was significantly higher than after LF stimulation (p = 0.005), which was mainly attributable to a higher amplitude of the peristaltic waves (p = 0.003). CONCLUSION: We provide evidence that 4-h of taVNS influences gastric motility in healthy human participants for the first time using rtMRI. HF stimulation is associated with higher amplitudes of peristaltic waves in the gastric antrum compared to LF stimulation. Further studies are needed to investigate the effect of different frequencies of taVNS and its therapeutic properties in conditions with impaired gastric motility.

Temporal encephaloceles in epilepsy patients and asymptomatic cases: Size may indicate epileptogenicity.

OBJECTIVE: This study was undertaken to identify temporal encephaloceles (TEs) and examine their characteristics in patients with temporal lobe epilepsy (TLE) and extratemporal lobe epilepsy (ETLE), as well as in asymptomatic cases. METHODS: Four hundred fifty-eight magnetic resonance imaging scans were examined retrospectively to identify TE in 157 patients with TLE, 150 patients with ETLE, and 151 healthy controls (HCs). RESULTS: At least one TE was identified in 9.6% of the TLE patients (n = 15, 95% confidence interval [CI] = 5.3%-15.3%), in 3.3% of patients with ETLE (n = 5, 95% CI = 1.1%-7.6%), and in 2.0% of the HCs (n = 3, 95% CI = .4%-5.7%), indicating a significantly higher frequency in patients with TLE compared to ETLE and HC subjects (p = .027, p = .005). Examining the characteristics of TEs in both asymptomatic and epilepsy patients, we found that TEs with a diameter of less than 6.25 mm were more likely to be asymptomatic, with a sensitivity of 91.7% and a specificity of 73.3% (area under the curve = .867, 95% CI = .723-1.00, p = .001). SIGNIFICANCE: Temporal encephaloceles may occur without presenting any clinical symptoms. Patients with TLE show a higher frequency of TEs compared to the ETLE and HC groups. According to our study, TE size could be used to suggest potential epileptogenicity.

Trust your gut: vagal nerve stimulation in humans improves reinforcement learning.

Whereas the effect of vagal nerve stimulation on emotional states is well established, its effect on cognitive functions is still unclear. Recent rodent studies show that vagal activation enhances reinforcement learning and neuronal dopamine release. The influence of vagal nerve stimulation on reinforcement learning in humans is still unknown. Here, we studied the effect of transcutaneous vagal nerve stimulation on reinforcement learning in eight long-standing seizure-free epilepsy patients, using a well-established forced-choice reward-based paradigm in a cross-sectional, within-subject study design. We investigated vagal nerve stimulation effects on overall accuracy using non-parametric cluster-based permutation tests. Furthermore, we modelled sub-components of the decision process using drift-diffusion modelling. We found higher accuracies in the vagal nerve stimulation condition compared to sham stimulation. Modelling suggests a stimulation-dependent increase in reward sensitivity and shift of accuracy-speed trade-offs towards maximizing rewards. Moreover, vagal nerve stimulation was associated with increased non-decision times suggesting enhanced sensory or attentional processes. No differences of starting bias were detected for both conditions. Accuracies in the extinction phase were higher in later trials of the vagal nerve stimulation condition, suggesting a perseverative effect compared to sham. Together, our results provide first evidence of causal vagal influence on human reinforcement learning and might have clinical implications for the usage of vagal stimulation in learning deficiency.

Hidradenitis Suppurativa is Associated with Symptoms of Keratoconjunctivitis Sicca.

AIM OF THE STUDY: Hidradenitis suppurativa (HS) and psoriasis vulgaris (PSO) are chronic inflammatory dermatoses in which proinflammatory cytokines, such as IL-17, play a central role. The prevalence of keratoconjunctivitis sicca (KCS) is commonly higher in PSO than in healthy individuals. This study was thus set up to investigate the prevalence of KCS among patients with HS. MATERIALS AND METHODS: In a cross-sectional study standardized tear film parameters and symptom-oriented questionnaires (OSDI, SPEED) were analyzed in a total of 71 subjects (HS n = 20, PSO n = 20, healthy controls n = 31). Additionally, IL-17 and MMP-9 in the tear film were analyzed. These parameters were correlated to the clinical severity of the skin disease. PSO patients served as inflammatory control group. RESULTS: There were statistically significant differences in OSDI (p = .003) and SPEED (p ≤ 0.001) between HS and the control group, but not between PSO and controls. For HS, there was a statistically significant correlation between symptoms (OSDI) and the severity of HS according to Hurley stage (p = .023). Tear film concentrations showed significantly increased levels of IL-17 (p = .018), but not MMP-9, in PSO alone compared to the control group. CONCLUSION: Data show that subjective complaints of KCS may be associated with HS and correlate with the severity of the respective Hurley stage, but do not involve alterations of tear film MMP-9 and IL-17. Clinicians should remain mindful that ocular complications in HS are often more vague than in psoriatic patients, but dry eye symptoms might be detrimental for the patients' quality of life.

[Drug interactions in dermatological systemic treatment]. / Wechselwirkungen in der dermatologischen Systemtherapie.

Severe pharmacological side effects have an occurrence of 5-7% and represent a frequent reason for hospital admission. The prevalence of undesired pharmacological side effects during hospitalization is even higher with approximately 11.5%. The causes are often interactions between drugs due to the polypharmacy of multimorbid older patients. On average, a 65-year-old male patient will simultaneously be taking 5 medications. Due to the increasing use of systemic drugs in dermatology and the simultaneously increasing polypharmacy, knowledge of interactions between medications is essential for dermatologists in order to avoid severe side effects of drugs. This article provides assistance in order to identify patients and medications with a high risk for severe interactions and, therefore, to avoid the occurrence of undesired effects or the reduction of the therapeutic effects of active substances. We would like to point out that this article deals with individual aspects and does not mean that the testing of individual drug interactions with interaction programs can be omitted. It should also not be neglected that in addition to prescription-only drugs, foodstuffs, dietary supplements and herbs can also lead to interactions with medications.

Examination of the Flynn effect in German patients with epilepsy assessed with the Wechsler Adult Intelligence Scale (WAIS) III and IV.

The Flynn effect describes an increase in intelligence quotient (IQ) in the general population of about 3 points per decade. While this effect is well established in healthy individuals, research exploring the link to brain pathologies is scarce. We investigated the Flynn effect in a German sample of 203 patients with epilepsy with left, right, and bilateral lesions. Intelligence quotient values were obtained using the Wechsler Adult Intelligence Scales (WAIS) III and IV. Our results showed a stable Flynn effect with nearly no difference in adjusted full scale IQ (FSIQ) scores (0.02 IQ points) between the WAIS-III and WAIS-IV samples. There were no significant interactions between the side of pathology and corrected IQ values. Our sample showed a tendency towards performing worse in the WAIS-IV in three out of four subscales independently of the Flynn effect, pointing out methodological differences between the newer Wechsler editions. However, although patients with bilateral lesions performed worst across all subscales, they exhibited a similar pattern as patients with lesions in the left or right hemisphere, indicating that also more severe forms of brain pathologies can profit from the mechanisms behind the Flynn effect.

Drug-Resistant Juvenile Myoclonic Epilepsy: Misdiagnosis of Progressive Myoclonus Epilepsy.

Juvenile myoclonic epilepsy (JME) is a common epilepsy syndrome characterized by bilateral myoclonic and tonic-clonic seizures typically starting in adolescence and responding well to medication. Misdiagnosis of a more severe progressive myoclonus epilepsy (PME) as JME has been suggested as a cause of drug-resistance. Medical records of the Epilepsy Center Hessen-Marburg between 2005 and 2014 were automatically selected using keywords and manually reviewed regarding the presence of a JME diagnosis at any timepoint. The identified patients were evaluated regarding seizure outcome and drug resistance according to ILAE criteria. 87/168 identified JME patients were seizure-free at last follow-up including 61 drug-responsive patients (group NDR). Seventy-eight patients were not seizure-free including 26 drug-resistant patients (group DR). Valproate was the most efficacious AED. The JME diagnosis was revised in 7 patients of group DR including 6 in whom the diagnosis had already been questioned or revised during clinical follow-up. One of these was finally diagnosed with PME (genetically confirmed Lafora disease) based on genetic testing. She was initially reviewed at age 29 yrs and considered to be inconsistent with PME. Intellectual disability (p = 0.025), cognitive impairment (p < 0.001), febrile seizures in first-degree relatives (p = 0.023) and prominent dialeptic seizures (p = 0.009) where significantly more frequent in group DR. Individuals with PME are rarely found among drug-resistant alleged JME patients in a tertiary epilepsy center. Even a very detailed review by experienced epileptologists may not identify the presence of PME before the typical features evolve underpinning the need for early genetic testing in drug-resistant JME patients.

Hemispheric language lateralization in presurgical patients with temporal lobe epilepsy: Improving the retest reliability of functional transcranial Doppler sonography.

Since its introduction, functional transcranial Doppler sonography (fTCD) has been extensively applied in research and clinical settings and has now become part of the routine presurgical work-up of patients with epilepsy. Because of its importance in planning neurosurgical interventions and predicting possible cognitive risks, the reproducibility of fTCD in determining hemispheric language lateralization (HLL) has to be ensured. In the present study, fTCD was performed twice in 33 initially lateralized patients with temporal lobe epilepsy (TLE) as part of their presurgical work-up, using a standard word generation paradigm. Initially, the standard analysis, including only the statistical examination of fTCD data, was applied, and a rather poor retest reliability of r = 0.41 was obtained (p = 0.017). Because of doubts concerning appropriate task performance in some patients, subsequently, a two-step data analysis was introduced, including an additional qualitative evaluation of fTCD data regarding (1) instruction-compliant task performance, (2) sufficient quality of the baseline phase, and (3) adequate increase in cerebral blood flow velocity (CBFV) during the activation phase. Attributable to a more valid interpretation of fTCD data after the application of the qualitative step, the reproducibility of HLL significantly improved (p = 0.007) to a high retest reliability of r = 0.84 (p < 0.000). In clinical settings, psychological and situational factors seem to strongly influence the reproducibility of fTCD determining HLL. Accordingly, we highly recommend the complementation of the standard statistical examination of fTCD data by an additional qualitative evaluation (two-step data analysis), as this extra security is particularly desirable because of its direct implications for the further evaluation of neurosurgical interventions. This article is part of the Special Issue "Individualized Epilepsy Management: Medicines, Surgery and Beyond".

Limitations of a Short Demographic Questionnaire for Bedside Estimation of Patients' Global Cognitive Functioning in Epilepsy Patients.

OBJECTIVES: The German socio-demographic estimation scale was developed by Jahn et al. (1) to quickly predict premorbid global cognitive functioning in patients. So far, it has been validated in healthy adults and has shown a good correlation with the full and verbal IQ of the Wechsler Adult Intelligence Scale (WAIS) in this group. However, there are no data regarding its use as a bedside test in epilepsy patients. METHODS: Forty native German speaking adult patients with refractory epilepsy were included. They completed a neuropsychological assessment, including a nine scale short form of the German version of the WAIS-III and the German socio-demographic estimation scale by Jahn et al. (1) during their presurgical diagnostic stay in our center. We calculated means, correlations, and the rate of concordance (range ±5 and ±7.5 IQ score points) between these two measures for the whole group, and a subsample of 19 patients with a global cognitive functioning level within 1 SD of the mean (IQ score range 85-115) and who had completed their formal education before epilepsy onset. RESULTS: The German demographic estimation scale by Jahn et al. (1) showed a significant mean overestimation of the global cognitive functioning level of eight points in the epilepsy patient sample compared with the short form WAIS-III score. The accuracy within a range of ±5 or ±7.5 IQ score points for each patient was similar to that of the healthy controls reported by Jahn et al. (1) in our subsample, but not in our whole sample. CONCLUSION: Our results show that the socio-demographic scale by Jahn et al. (1) is not sufficiently reliable as an estimation tool of global cognitive functioning in epilepsy patients. It can be used to estimate global cognitive functioning in a subset of patients with a normal global cognitive functioning level who have completed their formal education before epilepsy onset, but it does not reliably predict global cognitive functioning in epilepsy patients in general, who often do not fulfill these criteria. It is therefore not a useful tool to be applied in the general neuropsychological presurgical evaluation of epilepsy patients.

Brivaracetam in the Treatment of Patients with Epilepsy-First Clinical Experiences.

OBJECTIVES: To assess first clinical experiences with brivaracetam (BRV) in the treatment of epilepsies. METHODS: Data on patients treated with BRV from February to December 2016 and with at least one clinical follow-up were collected from electronic patient records. Data on safety and efficacy were evaluated retrospectively. RESULTS: In total, 93 patients were analyzed; 12 (12.9%) received BRV in monotherapy. The mean duration to follow-up was 4.85 months (MD = 4 months; SD = 3.63). Fifty-seven patients had more than one seizure per month at baseline and had a follow-up of more than 4 weeks; the rate of ≥50% responders was 35.1% (n = 20) in this group, of which five (8.8%) patients were newly seizure-free. In 50.5% (47/93), patients were switched from levetiracetam (LEV) to BRV, of which 43 (46.2%) were switched immediately. Adverse events (AE) occurred in 39.8%, with 22.6% experiencing behavioral and 25.8% experiencing non-behavioral AE. LEV-related AE (LEV-AE) were significantly reduced by switching to BRV. The discontinuation of BRV was reported in 26/93 patients (28%); 10 of those were switched back to LEV with an observed reduction of AE in 70%. For clinical reasons, 12 patients received BRV in monotherapy, 75% were seizure-free, and previous LEV-AE improved in 6/9 patients. BRV-related AE occurred in 5/12 cases, and five patients discontinued BRV. CONCLUSION: BRV seems to be a safe, easy, and effective option in the treatment of patients with epilepsy, especially in the treatment of patients who have psychiatric comorbidities and might not be good candidates for LEV treatment. BRV broadens the therapeutic spectrum and facilitates personalized treatment.

Quantification of mechanical dyssynchrony in growth restricted fetuses and normal controls using speckle tracking echocardiography (STE).

PURPOSE: To evaluate longitudinal mechanical dyssynchrony in normally grown fetuses by speckle tracking echocardiography (STE) and to compare longitudinal mechanical dyssynchrony in fetal growth restriction (FGR) with normal controls. MATERIALS AND METHODS: A prospective study was performed on 30 FGR and 62 normally grown fetuses, including 30 controls matched by gestational age, using STE and a transversal four-chamber view. Data analysis was carried out with a high frame rate of about 175 frames/s. Dyssynchrony was analyzed offline with QLab 9 (Philips Medical Systems, Andover, MA, USA) as time differences between peaks in strain of both ventricles and the septum. Inter- and intraventricular and intraseptal dyssynchrony were obtained and inter- and intraobserver reliability was analyzed. RESULTS: Longitudinal mechanical dyssynchrony was feasible in all cases, with high inter- and intraobserver reliability. Levels of inter- and intraventricular dyssynchrony were higher in the FGR than in the control group. CONCLUSION: Speckle tracking echocardiography (STE) is a reliable technique for cardiac function assessment in the fetal heart. Interventricular dyssynchrony could be a potential parameter for early detection of subclinical myocardial dysfunction before other parameters demand intervention. The future clinical role of longitudinal mechanical dyssynchrony needs to be verified in larger studies and with a technique customized for prenatal echocardiography.

Multivariate decoding of cerebral blood flow measures in a clinical model of on-going postsurgical pain.

Recent reports of multivariate machine learning (ML) techniques have highlighted their potential use to detect prognostic and diagnostic markers of pain. However, applications to date have focussed on acute experimental nociceptive stimuli rather than clinically relevant pain states. These reports have coincided with others describing the application of arterial spin labeling (ASL) to detect changes in regional cerebral blood flow (rCBF) in patients with on-going clinical pain. We combined these acquisition and analysis methodologies in a well-characterized postsurgical pain model. The principal aims were (1) to assess the classification accuracy of rCBF indices acquired prior to and following surgical intervention and (2) to optimise the amount of data required to maintain accurate classification. Twenty male volunteers, requiring bilateral, lower jaw third molar extraction (TME), underwent ASL examination prior to and following individual left and right TME, representing presurgical and postsurgical states, respectively. Six ASL time points were acquired at each exam. Each ASL image was preceded by visual analogue scale assessments of alertness and subjective pain experiences. Using all data from all sessions, an independent Gaussian Process binary classifier successfully discriminated postsurgical from presurgical states with 94.73% accuracy; over 80% accuracy could be achieved using half of the data (equivalent to 15 min scan time). This work demonstrates the concept and feasibility of time-efficient, probabilistic prediction of clinically relevant pain at the individual level. We discuss the potential of ML techniques to impact on the search for novel approaches to diagnosis, management, and treatment to complement conventional patient self-reporting.

Pharmacologic modulation of hand pain in osteoarthritis: a double-blind placebo-controlled functional magnetic resonance imaging study using naproxen.

OBJECTIVE: In an attempt to shed light on management of chronic pain conditions, there has long been a desire to complement behavioral measures of pain perception with measures of underlying brain mechanisms. Using functional magnetic resonance imaging (fMRI), we undertook this study to investigate changes in brain activity following the administration of naproxen or placebo in patients with pain related to osteoarthritis (OA) of the carpometacarpal (CMC) joint. METHODS: A placebo-controlled, double-blind, 2-period crossover study was performed in 19 individuals with painful OA of the CMC joint of the right hand. Following placebo or naproxen treatment periods, a functionally relevant task was performed, and behavioral measures of the pain experience were collected in identical fMRI examinations. Voxelwise and a priori region of interest analyses were performed to detect between-period differences in brain activity. RESULTS: Significant reductions in brain activity following treatment with naproxen, compared to placebo, were observed in brain regions commonly associated with pain perception, including the bilateral primary somatosensory cortex, thalamus, and amygdala. Significant relationships between changes in perceived pain intensity and changes in brain activity were also observed in brain regions previously associated with pain intensity. CONCLUSION: This study demonstrates the sensitivity of fMRI to detect the mechanisms underlying treatments of known efficacy. The data illustrate the enticing potential of fMRI as an adjunct to self-report for detecting early signals of efficacy of novel therapies, both pharmacologic and nonpharmacologic, in small numbers of individuals with persistent pain.

Emotional well-being and time pressure.

We propose a conceptual model of how time pressure affects emotional well-being associated with mundane routine activities. A selective review of research in several areas affirms the plausibility of the conceptual model, which posits negative effects on emotional well-being of insufficient time allocated to restorative and other activities instrumental for attaining desirable work, family life, and leisure goals. Previous research also affirms that practicing time management can have indirect positive effects by decreasing time pressure, whereas material wealth can have both negative indirect effects and positive indirect effects by increasing and decreasing time pressure, respectively. Several issues remain to be studied empirically. The conceptual model is a ground for additional, preferably cross-cultural, research.