Religious Coping, Resilience, and Military Spouse Mental Health.

INTRODUCTION: Military spouses play a key role in the military family and contribute to military readiness. Despite their influence, they are an understudied population. Previous research has identified military spouses as a vulnerable group considering their unique life stressors and high mental distress; thus, it is critical to identify potential protective factors for military spouses. However, there is a lack of research exploring the role of religious coping and resilience in mental health outcomes of military spouses. The purpose of this study was to evaluate the effect of religious coping on depression, anxiety, and stress, and the extent to which the effect is mediated by resilience. MATERIALS AND METHODS: A total of 1,079 military spouses completed self-administered surveys online. The questionnaires assessed demographic factors, depression, anxiety, stress, religious coping, and resilience. Zero-order correlations and descriptive statistics were analyzed. Additionally, multiple linear regression was utilized to investigate the extent to which resilience mediated the relationship between religious coping and mental health outcomes. RESULTS: The results indicate high levels of depression, anxiety, and stress among military spouses. Religious coping had significant effects on mental distress, such that increases in religious coping corresponded to decreases in depression (ß = -3.30), anxiety (ß = -1.89) and stress (ß = -1.58). Mediation analyses indicated resilience significantly mediated the relationship between religious coping and depression (95% CI [-1.38, -.431]), anxiety (95% CI [-1.23, -.376]), and stress (95% CI [-1.328, -0.420]). For military spouses, religious coping was associated with increased resilience, which was subsequently associated with reduced mental distress. CONCLUSIONS: This study draws attention to the role of religious coping and resilience in mental health outcomes for military spouses. Considering the role of military spouses in supporting service members, future research should explore how to strengthen military spouses' religious coping and resilience to mitigate mental distress, thereby facilitating service member success and military readiness.

Do psychotropic drugs cause seizures?

Patients with epilepsy often present with concurrent psychiatric disorders, posing unique challenges for healthcare providers. This review explores the intricate relationship between psychiatric comorbidities, epilepsy, and psychotropic medications to inform clinical decision-making. The bidirectional association between epilepsy and psychiatric conditions complicates treatment, with psychiatric symptoms preceding or following seizure onset. The review discusses the seizure risks associated with antidepressants, CNS stimulants, and antipsychotics, shedding light on both historical perspectives and recent empirical evidence. Antidepressants, particularly tricyclic antidepressants (TCAs), are known to pose seizure risks, while newer agents like selective serotonin reuptake inhibitors (SSRIs) exhibit lower incidences and even potential anticonvulsant effects. Contrary to common beliefs, CNS stimulants used in attention-deficit/hyperactivity disorder (ADHD) treatment show efficacy without significantly increasing seizure risk. However, the association between ADHD and seizures warrants careful consideration. Among antipsychotics, clozapine stands out for its heightened seizure risks, especially during titration and at high doses, necessitating close monitoring and individualized approaches. Understanding the nuanced seizure risks associated with different psychotropic medications is crucial for optimizing patient care and minimizing iatrogenic seizures in this vulnerable population. By recognizing the complexities of psychiatric comorbidities in epilepsy and considering the unique challenges they pose, healthcare providers can make informed decisions to enhance patient safety and treatment outcomes. This review offers practical insights to guide clinicians in navigating the intricate landscape of managing psychiatric comorbidities in patients with epilepsy.

Trends in management of patients with new-onset refractory status epilepticus (NORSE) from 2016 to 2023: An interim analysis.

In response to the evolving treatment landscape for new-onset refractory status epilepticus (NORSE) and the publication of consensus recommendations in 2022, we conducted a comparative analysis of NORSE management over time. Seventy-seven patients were enrolled by 32 centers, from July 2016 to August 2023, in the NORSE/FIRES biorepository at Yale. Immunotherapy was administered to 88% of patients after a median of 3 days, with 52% receiving second-line immunotherapy after a median of 12 days (anakinra 29%, rituximab 25%, and tocilizumab 19%). There was an increase in the use of second-line immunotherapies (odds ratio [OR] = 1.4, 95% CI = 1.1-1.8) and ketogenic diet (OR = 1.8, 95% CI = 1.3-2.6) over time. Specifically, patients from 2022 to 2023 more frequently received second-line immunotherapy (69% vs 40%; OR = 3.3; 95% CI = 1.3-8.9)-particularly anakinra (50% vs 13%; OR = 6.5; 95% CI = 2.3-21.0), and the ketogenic diet (OR = 6.8; 95% CI = 2.5-20.1)-than those before 2022. Among the 27 patients who received anakinra and/or tocilizumab, earlier administration after status epilepticus onset correlated with a shorter duration of status epilepticus (ρ = .519, p = .005). Our findings indicate an evolution in NORSE management, emphasizing the increasing use of second-line immunotherapies and the ketogenic diet. Future research will clarify the impact of these treatments and their timing on patient outcomes.

Comparative analysis of patients with new onset refractory status epilepticus preceded by fever (febrile infection-related epilepsy syndrome) versus without prior fever: An interim analysis.

Febrile infection-related epilepsy syndrome (FIRES) is a subset of new onset refractory status epilepticus (NORSE) that involves a febrile infection prior to the onset of the refractory status epilepticus. It is unclear whether FIRES and non-FIRES NORSE are distinct conditions. Here, we compare 34 patients with FIRES to 30 patients with non-FIRES NORSE for demographics, clinical features, neuroimaging, and outcomes. Because patients with FIRES were younger than patients with non-FIRES NORSE (median = 28 vs. 48 years old, p = .048) and more likely cryptogenic (odds ratio = 6.89), we next ran a regression analysis using age or etiology as a covariate. Respiratory and gastrointestinal prodromes occurred more frequently in FIRES patients, but no difference was found for non-infection-related prodromes. Status epilepticus subtype, cerebrospinal fluid (CSF) and magnetic resonance imaging findings, and outcomes were similar. However, FIRES cases were more frequently cryptogenic; had higher CSF interleukin 6, CSF macrophage inflammatory protein-1 alpha (MIP-1a), and serum chemokine ligand 2 (CCL2) levels; and received more antiseizure medications and immunotherapy. After controlling for age or etiology, no differences were observed in presenting symptoms and signs or inflammatory biomarkers, suggesting that FIRES and non-FIRES NORSE are very similar conditions.

Implementer report: ICD-10 code F44.5 review for functional seizure disorder.

OBJECTIVE: The study aimed to measure the validity of International Classification of Diseases, 10th Edition (ICD-10) code F44.5 for functional seizure disorder (FSD) in the Veterans Affairs Connecticut Healthcare System electronic health record (VA EHR). METHODS: The study used an informatics search tool, a natural language processing algorithm and a chart review to validate FSD coding. RESULTS: The positive predictive value (PPV) for code F44.5 was calculated to be 44%. DISCUSSION: ICD-10 introduced a specific code for FSD to improve coding validity. However, results revealed a meager (44%) PPV for code F44.5. Evaluation of the low diagnostic precision of FSD identified inconsistencies in the ICD-10 and VA EHR systems. CONCLUSION: Information system improvements may increase the precision of diagnostic coding by clinicians. Specifically, the EHR problem list should include commonly used diagnostic codes and an appropriately curated ICD-10 term list for 'seizure disorder,' and a single ICD code for FSD should be classified under neurology and psychiatry.

Neuropathology of New-Onset Refractory Status Epilepticus (NORSE).

New-Onset Refractory Status Epilepticus (NORSE), including its subtype with a preceding febrile illness known as FIRES (Febrile Infection-Related Epilepsy Syndrome), is one of the most severe forms of status epilepticus. Despite an extensive workup (clinical evaluation, EEG, imaging, biological tests), the majority of NORSE cases remain unexplained (i.e., "cryptogenic NORSE"). Understanding the pathophysiological mechanisms underlying cryptogenic NORSE and the related long-term consequences is crucial to improve patient management and preventing secondary neuronal injury and drug-resistant post-NORSE epilepsy. Previously, neuropathological evaluations conducted on biopsies or autopsies have been found helpful for identifying the etiologies of some cases that were previously of unknown cause. Here, we summarize the findings of studies reporting neuropathology findings in patients with NORSE, including FIRES. We identified 64 cryptogenic cases and 66 neuropathology tissue samples, including 37 biopsies, 18 autopsies, and seven epilepsy surgeries (the type of tissue sample was not detailed for 4 cases). We describe the main neuropathology findings and place a particular emphasis on cases for which neuropathology findings helped establish a diagnosis or elucidate the pathophysiology of cryptogenic NORSE, or on described cases in which neuropathology findings supported the selection of specific treatments for patients with NORSE.

Review and standard operating procedures for collection of biospecimens and analysis of biomarkers in new onset refractory status epilepticus.

New onset refractory status epilepticus (NORSE), including its subtype with a preceding febrile illness known as febrile infection-related epilepsy syndrome (FIRES), is one of the most severe forms of status epilepticus. The exact causes of NORSE are currently unknown, and there is so far no disease-specific therapy. Identifying the underlying pathophysiology and discovering specific biomarkers, whether immunologic, infectious, genetic, or other, may help physicians in the management of patients with NORSE. A broad spectrum of biomarkers has been proposed for status epilepticus patients, some of which were evaluated for patients with NORSE. Nonetheless, none has been validated, due to significant variabilities in study cohorts, collected biospecimens, applied analytical methods, and defined outcome endpoints, and to small sample sizes. The NORSE Institute established an open NORSE/FIRES biorepository for health-related data and biological samples allowing the collection of biospecimens worldwide, promoting multicenter research and sharing of data and specimens. Here, we suggest standard operating procedures for biospecimen collection and biobanking in this rare condition. We also propose criteria for the appropriate use of previously collected biospecimens. We predict that the widespread use of standardized procedures will reduce heterogeneity, facilitate the future identification of validated biomarkers for NORSE, and provide a better understanding of the pathophysiology and best clinical management for these patients.

The seasonality of new-onset refractory status epilepticus (NORSE).

The etiology of new-onset refractory status epilepticus (NORSE), including its subtype with prior fever known as FIRES (febrile infection-related epilepsy syndrome), remains uncertain. Several arguments suggest that NORSE is a disorder of immunity, likely post-infectious. Consequently, seasonal occurrence might be anticipated. Herein we investigated if seasonality is a notable factor regarding NORSE presentation. We combined four different data sets with a total of 342 cases, all from the northern hemisphere, and 62% adults. The incidence of NORSE cases differed between seasons (p = .0068) and was highest in the summer (32.2%) (p = .0022) and lowest in the spring (19.0%, p = .010). Although both FIRES and non-FIRES cases occurred most commonly during the summer, there was a trend toward FIRES cases being more likely to occur in the winter than non-FIRES cases (OR 1.62, p = .071). The seasonality of NORSE cases differed according to the etiology (p = .024). NORSE cases eventually associated with autoimmune/paraneoplastic encephalitis occurred most frequently in the summer (p = .032) and least frequently in the winter (p = .047), whereas there was no seasonality for cryptogenic cases. This study suggests that NORSE overall and NORSE related to autoimmune/paraneoplastic encephalitis are more common in the summer, but that there is no definite seasonality in cryptogenic cases.

Cytokines in New-Onset Refractory Status Epilepticus Predict Outcomes.

OBJECTIVE: The objective of this study was to investigate inflammation using cerebrospinal fluid (CSF) and serum cytokines/chemokines in patients with new-onset refractory status epilepticus (NORSE) to better understand the pathophysiology of NORSE and its consequences. METHODS: Patients with NORSE (n = 61, including n = 51 cryptogenic), including its subtype with prior fever known as febrile infection-related epilepsy syndrome (FIRES), were compared with patients with other refractory status epilepticus (RSE; n = 37), and control patients without SE (n = 52). We measured 12 cytokines/chemokines in serum or CSF samples using multiplexed fluorescent bead-based immunoassay detection. Cytokine levels were compared between patients with and without SE, and between the 51 patients with cryptogenic NORSE (cNORSE) and the 47 patients with a known-etiology RSE (NORSE n = 10, other RSE n = 37), and correlated with outcomes. RESULTS: A significant increase of IL-6, TNF-α, CXCL8/IL-8, CCL2, MIP-1α, and IL-12p70 pro-inflammatory cytokines/chemokines was observed in patients with SE compared with patients without SE, in serum and CSF. Serum innate immunity pro-inflammatory cytokines/chemokines (CXCL8, CCL2, and MIP-1α) were significantly higher in patients with cNORSE compared to non-cryptogenic RSE. Patients with NORSE with elevated innate immunity serum and CSF cytokine/chemokine levels had worse outcomes at discharge and at several months after the SE ended. INTERPRETATION: We identified significant differences in innate immunity serum and CSF cytokine/chemokine profiles between patients with cNORSE and non-cryptogenic RSE. The elevation of innate immunity pro-inflammatory cytokines in patients with NORSE correlated with worse short- and long-term outcomes. These findings highlight the involvement of innate immunity-related inflammation, including peripherally, and possibly of neutrophil-related immunity in cNORSE pathogenesis and suggest the importance of utilizing specific anti-inflammatory interventions. ANN NEUROL 2023;94:75-90.