Immune response in blood before and after epileptic and psychogenic non-epileptic seizures.
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ABSTRACT:
SUBMITTER: Ahl M
PROVIDER: S-EPMC9988551 | biostudies-literature | 2023 Mar
REPOSITORIES: biostudies-literature
Publications
Immune response in blood before and after epileptic and psychogenic non-epileptic seizures.
Ahl Matilda M Taylor Marie K MK Avdic Una U Lundin Anna A Andersson My M Amandusson Åsa Å Kumlien Eva E Compagno Strandberg Maria M Ekdahl Christine T CT
Heliyon 20230221 3
<b>Inflammatory processes</b> may provoke epileptic seizures and seizures may promote an immune reaction. Hence, the systemic immune reaction is a tempting diagnostic and prognostic marker in epilepsy. We explored the immune response before and after epileptic and psychogenic non-epileptic seizures (PNES). Serum samples collected from patients with videoEEG-verified temporal or frontal lobe epilepsy (TLE or FLE) or TLE + PNES showed increased interleukin-6 (IL-6) levels in between seizures (inte ...[more]
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Project description:ObjectiveOur aim was to conduct a pilot randomized controlled trial of a novel cognitive behaviorally based intervention for pediatric PNES called Retraining and Control Therapy (ReACT).MethodsParticipants were randomized to receive either eight sessions of ReACT or supportive therapy, and participants completed follow-up visits at 7- and 60-days posttreatment. The primary outcome measure was PNES frequency at 7-days posttreatment. Eligibility criteria included children with video-EEG confirmed PNES and participant/parent or guardian willingness to participate in treatment. Exclusion criteria included substance use, psychosis, and severe intellectual disability. Forty-two patients were assessed for eligibility and 32 were randomized. ReACT aimed to retrain classically conditioned, involuntary PNES by targeting catastrophic symptom expectations and a low sense of control over symptoms using principles of habit reversal. Supportive therapy was based on the assumption that relief from stress or problems can be achieved by discussion with a therapist.ResultsTwenty-nine participants (Mage = 15.1 years, SDage = 2.5; 72.2% female; 57.1% Caucasian, 28.6% African American) completed 7-days postprocedures. For PNES frequency, the Wilcoxon Rank Sum test statistic was 273.5 yielding a normal approximation of Z = 4.725 (P < 0.0001), indicating a significant improvement in PNES frequency for ReACT at 7-days posttreatment compared to supportive therapy. Participants with PNES in the 7-days posttreatment were removed from the study for additional treatment, resulting in no 60-day follow-up data for supportive therapy.InterpretationReACT resulted in significantly greater PNES reduction than supportive therapy, with 100% of patients experiencing no PNES in 7 days after ReACT. Additionally, 82% remained PNES-free for 60 days after ReACT.
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Project description:Psychogenic non-epileptic seizures (PNES) may resemble epileptic seizures but are not caused by epileptic activity. However, the analysis of electroencephalogram (EEG) signals with entropy algorithms could help identify patterns that differentiate PNES and epilepsy. Furthermore, the use of machine learning could reduce the current diagnosis costs by automating classification. The current study extracted the approximate sample, spectral, singular value decomposition, and Renyi entropies from interictal EEGs and electrocardiograms (ECG)s of 48 PNES and 29 epilepsy subjects in the broad, delta, theta, alpha, beta, and gamma frequency bands. Each feature-band pair was classified by a support vector machine (SVM), k-nearest neighbour (kNN), random forest (RF), and gradient boosting machine (GBM). In most cases, the broad band returned higher accuracy, gamma returned the lowest, and combining the six bands together improved classifier performance. The Renyi entropy was the best feature and returned high accuracy in every band. The highest balanced accuracy, 95.03%, was obtained by the kNN with Renyi entropy and combining all bands except broad. This analysis showed that entropy measures can differentiate between interictal PNES and epilepsy with high accuracy, and improved performances indicate that combining bands is an effective improvement for diagnosing PNES from EEGs and ECGs.
| S-EPMC9601450 | biostudies-literature
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Project description:Non-convulsive status epilepticus (NCSE) is a prolonged epileptic seizure with subtle symptoms that may delay clinical diagnosis. Emerging experimental evidence shows brain pathology and epilepsy development following NCSE. New diagnostic/prognostic tools are therefore needed for earlier and better stratification of treatment. Here we examined whether NCSE initiates a peripheral immune response in blood serum from rats that experienced electrically-induced NCSE. ELISA analysis showed an acute transient increase in serum protein levels including interleukin-6 6 h post-NCSE, similar to the immune reaction in the brain. At 4 weeks post-NCSE, when 75% of rats subjected to NCSE had also developed spontaneous seizures, several immune proteins were altered. In particular, markers associated with microglia, macrophages and antigen presenting cells, such as CD68, MHCII, and galectin-3, were increased and the T-cell marker CD4 was decreased in serum compared to both non-stimulated controls and NCSE rats without spontaneous seizures, without correlation to interictal epileptiform activity. Analyses of serum following intracerebral injection of lipopolysaccharide (LPS) showed an acute increase in interleukin-6, but at 4 weeks unaltered levels of MHCII and galectin-3, an increase in CD8 and CD11b and a decrease in CD68. None of the increased serum protein levels after NCSE or LPS could be confirmed in spleen tissue. Our data identifies the possibility to detect peripheral changes in serum protein levels following NCSE, which may be related to the development of subsequent spontaneous seizures.
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Project description:ObjectiveTo study the outcome of patients with psychogenic non-epileptic seizures (PNES) after their diagnosis in the epilepsy monitoring unit (EMU).MethodsPatients diagnosed in our EMU with definite PNES between January 2009 and May 2023 were contacted by phone, and those who agreed to participate were asked a set of predetermined questions. Comparative analyses were carried out on several variables before and after diagnosis: number of participants with daily PNES, number of visits to the emergency department, number of participants who consulted their general practitioner or a neurologist outside of a scheduled follow-up, number of participants who took antiseizure medications (ASMs) or psychotropic drugs, and employment status.ResultsOut of the 103 patients with a definite diagnosis of PNES, 61 patients (79% female) accepted to participate in our study. The median age at PNES onset was 35 years, and the median delay to diagnosis was 3 years. Almost two-thirds (62%) were receiving ASMs and 40% psychotropic drugs. The mean stay at the EMU was 5 days. PNES diagnosis was explained to almost all patients (97%) by the end of their EMU stay and was well-accepted by most (89%). When contacted, 46% of participants no longer had PNES; 32% mentioned that their PNES had ceased immediately upon communication of the diagnosis. The median follow-up duration was 51 months. Fewer patients had daily seizures after the diagnosis (18 vs. 38%; p < 0.0455). Similarly, the median number of emergency department visits was significantly lower (0 vs. 2; p < 0.001). Only 17 patients consulted their general practitioner (vs. 40, p < 0.001) and 20 a neurologist (vs. 55, p < 0.001) after a PNES attack outside of a scheduled follow-up. The use of ASMs was also significantly reduced from 70 to 33% (p < 0.01), with only one still taking an ASM for its antiseizure properties. Significantly more participants were working at last follow-up than at PNES diagnosis (49 vs. 25%; p < 0.001).ConclusionOur study revealed a relatively favorable long-term outcome of definite PNES diagnosed in the EMU that translated in significant reductions in PNES frequency, health care utilization and ASM use, as well as a significant increase in employment rate.
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Project description:BackgroundNeuroinflammation may contribute to the pathophysiology of psychogenic non-epileptic seizures (PNES). However, it is unclear whether and to what degree comorbid psychiatric symptoms explain this association. In this study, we investigated the neuroinflammatory signature of PNES and how it compares to that of people with psychiatric conditions (PwPCs).MethodsWe prospectively assessed differences in neurite density (NDI), orientation dispersion (ODI), and isotropic diffusion (F-ISO) in 23 participants with PNES and 27 PwPCs, and their relationships to serum levels of tumor necrosis factor (TNF)-α, TNF receptor 1 (TNF-R1), TNF-related apoptosis-inducing ligand (TRAIL), interleukin (IL)-6, intercellular adhesion molecule (ICAM)-1, and monocyte chemoattractant protein (MCP)-1 using voxelwise multiple linear regressions. Pearson correlations between serum biomarkers and clinical symptoms were also obtained.ResultsThere were no white matter (WM) microstructural differences between groups. In PNES, TNF-R1 was negatively associated with NDI in the right uncinate fasciculus (UF) and positively associated with F-ISO in the left UF. IL-6 was positively associated with NDI and negatively with F-ISO in the left UF. ICAM-1 was positively associated with ODI in the left UF. TNF-α was negatively associated with ODI in the left cingulum bundle. The opposite relationships were observed in PwPCs. Higher TNF-R1 was associated with higher depression, anxiety, lower emotional quality of life, and higher levels of disability in PNES.ConclusionsFor the first time, we report relationships between peripheral inflammatory biomarkers and WM integrity in PNES, including abnormalities in the UF and cingulum bundle. Our results suggest that serum biomarkers of inflammation may, with additional studies, become a useful aid to PNES diagnosis, especially in settings where video-EEG is not available. The lack of group differences in WM microstructure suggests that previously identified WM abnormalities in PNES versus healthy controls may be related to psychological comorbidities of PNES.
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Project description:Although various imaging studies have focused on detecting the cerebral function underlying psychogenic non-epileptic seizures (PNES), the nature of PNES remains poorly understood. In this study, we combined the resting state fMRI with fractional amplitude of low-frequency fluctuations (fALFF) and functional connectivity based on the seed voxel linear correlation approach to examine the alterations of regional and inter-regional network cerebral functions in PNES. A total of 20 healthy controls and 18 patients were enrolled. The PNES patients showed significantly increased fALFF mainly in the dorsolateral prefrontal cortex (DLPFC), parietal cortices, and motor areas, as well as decreased fALFF in the triangular inferior frontal gyrus. Thus, our results add to literature suggesting abnormalities of neural synchrony in PNES. Moreover, PNES exhibited widespread inter-regional neural network deficits, including increased (DLPFC, sensorimotor, and limbic system) and decreased (ventrolateral prefrontal cortex) connectivity, indicating that changes in the regional cerebral function are related to remote inter-regional network deficits. Correlation analysis results revealed that the connectivity between supplementary motor area and anterior cingulate cortex correlated with the PNES frequency, further suggesting the skewed integration of synchronous activity could predispose to the occurrence of PNES. Our findings provided novel evidence to investigate the pathophysiological mechanisms of PNES.
| S-EPMC4480007 | biostudies-literature
Project description:Psychogenic Non-epileptic Seizures (PNES) are 'medically unexplained' seizure-like episodes which superficially resemble epileptic seizures but which are not caused by epileptiform discharges in the brain. While many experts see PNES disorder as a multifactorial biopsychosocial condition, little is known about the neurobiological processes which may predispose, precipitate and/or perpetuate PNES symptomology. This systematic meta-review advances our knowledge and understanding of the neurobiological correlates of PNES by providing an up-to-date assessment of neuroimaging studies performed on individuals with PNES. Although the results presented appear inconclusive, they are consistent with an association between structural and functional brain abnormalities and PNES. These findings have implications for the way in which we think about this "medically unexplained" disorder and how we communicate the diagnosis to patients. However, it is also evident that neuroimaging studies in this area suffer from a number of significant limitations and future larger studies will need to better address these if we are to improve our understanding of the neurobiological correlates of predisposition to and/or manifestation of PNES.
| S-EPMC5544493 | biostudies-other
Project description:ObjectiveTo determine the epidemiology of prolonged psychogenic non-epileptic seizures (pPNES) misdiagnosed as status epilepticus, as well as the risks associated with non-indicated treatment.MethodsWe performed an individual patient data analysis from the Rapid Anticonvulsant Medication Prior to Arrival Trial (RAMPART) and the Established Status Epilepticus Treatment Trial (ESETT) to assess incidence, patient characteristics and clinical course of misdiagnosed pPNES.ResultsAmong 980 patients aged 8 years or older diagnosed and treated for status epilepticus in RAMPART and ESETT, 79 (8.1%) were discharged with a final diagnosis of pPNES. The relative incidence was highest in adolescents and young adults (20.1%). The typical female preponderance seen in that age bracket was not evident in children and older adults. Adverse effects, including respiratory depression and intubation, were documented in 26% of patients with pPNES receiving benzodiazepines in RAMPART and 33% of patients receiving additional second-line medication in ESETT. In ESETT, patients who were treated with benzodiazepines before hospital admission had higher rates of unresponsiveness and severe adverse effects than those treated after admission, suggesting cumulative effects of accelerated treatment momentum. Across trials, one in five patients with pPNES were admitted to an intensive care unit.ConclusionsMisdiagnosis and treatment of pPNES as status epilepticus are a common and widespread problem with deleterious consequences. Mitigating it will require training of emergency staff in semiological diagnosis. Status epilepticus response protocols should incorporate appropriate diagnostic re-evaluations at each step of treatment escalation, especially in clinical trials.
| S-EPMC8606439 | biostudies-literature