Neuroinflammation as a pathophysiological factor in the development and maintenance of functional seizures: A hypothesis

Sharma, Ayushe A.; Szaflarski, Jerzy P.

doi:10.1016/j.ebr.2021.100496

Cited by 15 publications

(18 citation statements)

References 88 publications

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“…Accordingly, novel comparisons between the diffusion tractography metrics and the mental health assessments in the current study suggest that the lower health of the left UF in FS does not appear attributable to psychopathology. This finding raises the possibility that the differences may be related to the FNSD/CD, having controlled for TBI, or that they may be a preexisting factor that predisposes patients to the development of FS 43 …”

Section: Discussionmentioning

confidence: 99%

Decreased uncinate fasciculus integrity in functional seizures following traumatic brain injury

Byington,

Goodman,

Allendorfer

et al. 2024

Epilepsia

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ObjectiveThe uncinate fasciculus (UF) has been implicated previously in contributing to the pathophysiology of functional (nonepileptic) seizures (FS). FS are frequently preceded by adverse life events (ALEs) and present with comorbid psychiatric symptoms, yet neurobiological correlates of these factors remain unclear. To address this gap, using advanced diffusion magnetic resonance imaging (dMRI), UF tracts in a large cohort of patients with FS and pre‐existing traumatic brain injury (TBI + FS) were compared to those in patients with TBI without FS (TBI‐only). We hypothesized that dMRI measures in UF structural connectivity would reveal UF differences when controlling for TBI status. Partial correlation tests assessed the potential relationships with psychiatric symptom severity measures.MethodsParticipants with TBI‐only (N = 46) and TBI + FS (N = 55) completed a series of symptom questionnaires and MRI scanning. Deterministic tractography via diffusion spectrum imaging (DSI) was implemented in DSI studio (https://dsi‐studio.labsolver.org) with q‐space diffeomorphic reconstruction (QSDR), streamline production, and manual segmentation to assess bilateral UF integrity. Fractional anisotropy (FA), radial diffusivity (RD), streamline counts, and their respective asymmetry indices (AIs) served as estimates of white matter integrity.ResultsCompared to TBI‐only, TBI + FS participants demonstrated decreased left hemisphere FA and RD asymmetry index (AI) for UF tracts (both p < .05, false discovery rate [FDR] corrected). Additionally, TBI + FS reported higher symptom severity in depression, anxiety, and PTSD measures (all p < .01). Correlation tests comparing UF white matter integrity differences to psychiatric symptom severity failed to reach criteria for significance (all p > .05, FDR corrected).SignificanceIn a large, well‐characterized sample, participants with FS had decreased white matter health after controlling for the history of TBI. Planned follow‐up analysis found no evidence to suggest that UF connectivity measures are a feature of group differences in mood or anxiety comorbidities for FS. These findings suggest that frontolimbic structural connectivity may play a role in FS symptomology, after accounting for prior ALEs and comorbid psychopathology severity.

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Section: Discussionmentioning

confidence: 99%

Decreased uncinate fasciculus integrity in functional seizures following traumatic brain injury

Byington,

Goodman,

Allendorfer

et al. 2024

Epilepsia

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“…Of particular interest with regard to aberrant neural network function is the growing understanding that ACEs interact with inflammation -the immune-inflammatory component of the stress system -to alter brain maturation and to increase vulnerability for a broad range of symptoms and psychiatric disorders (Andersen, 2022). In the field of FND, ACE-related neuroinflammatory changes are hypothesised to contribute to neural network dysregulation (Radmanesh et al, 2020;Sharma and Szaflarski, 2021). It Australian & New Zealand Journal of Psychiatry, 57( 1) is likely that the role of neuroinflammation in FND will be an important topic of research in the decades to come.…”

Section: Discussionmentioning

confidence: 99%

“…Comorbid pain and non-specific functional symptoms – fatigue, dizziness, nausea, disrupted sleep – are common (Ani et al, 2013), as are anxiety or depression, which are present in 22–80% of cases (Vassilopoulos et al, 2022). Within paediatrics, the current understanding of FND is that stress system activation and dysregulation play a central role in generating these symptoms (Apazoglou et al, 2017; Kozlowska, 2017; Kozlowska et al, 2020; Sharma and Szaflarski, 2021). Of particular relevance in this context are the stress system components that are embedded within the brain and that modulate neural network function (Agorastos et al, 2019; Andersen, 2022; Apazoglou et al, 2017; Frank et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Cortisol and α-amylase awakening response in children and adolescents with functional neurological (conversion) disorder

Chung

Mukerji

Kozlowska

2022

Aust N Z J Psychiatry

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Objective: Stress system dysregulation is considered to have an important role in the aetiology of paediatric functional neurological (conversion) disorder. This study examined salivary cortisol and α-amylase awakening responses in children with functional neurological disorder to determine activation patterns of the hypothalamic–pituitary–adrenal axis and sympathetic system. A healthy cortisol awakening response involves a robust increase in cortisol within 30 minutes of awakening. Alpha-amylase awakening response is variable in children. Methods: Cortisol and α-amylase were measured in saliva from 32 patients with functional neurological disorder (26 girls and 6 boys, aged 11.3−16.1 years) and 31 healthy controls (23 girls and 8 boys, aged 8.6–17.7 years). Saliva samples were collected using a Salivette sampling device at two time points – upon awakening and 30 minutes after awakening. Results: Patients with functional neurological disorder showed a decrease in cortisol awakening response (–4 nmol.min/L) and controls showed an increase (107 nmol.min/L), t(55) = –.4.6, p < 0.001. Within the functional neurological disorder group, 57% showed an attenuated cortisol awakening response and 43% showed an obliterated/reversed cortisol awakening response: Cortisol awakening response was negatively correlated with adverse childhood experiences, r(58) = –0.6, p = 0.002, and subjective distress (total Depression Anxiety and Stress Scales score), r(58) = –0.4, p = 0.050. In controls, cortisol awakening response showed no correlation with adverse childhood experiences and a positive correlation with subjective distress, r(56) = 0.4, p = 0.023. Total cortisol remained similar between the functional neurological disorder and control group. No significant differences were observed between the functional neurological disorder and control group in any of the α-amylase analyses. Discussion: The results suggest dysregulation of the hypothalamic–pituitary–adrenal axis in children with functional neurological disorder. Hypothalamic–pituitary–adrenal dysregulation in children with functional neurological disorder may contribute to comorbid symptoms of fatigue, sleep disturbance and subjective loss of well-being because circadian rhythms and energy metabolism are disrupted. Hypothalamic–pituitary–adrenal dysregulation – and changes in glucocorticoid (cortisol) signalling at the molecular level – may also contribute to increased vulnerability for functional neurological disorder symptoms because of epigenetically mediated changes to neural networks implicated in functional neurological disorder.

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“…Medical studies hold that fear processing causes neuroinflammatory changes that lead to secondary trauma development (Sharma and Szaflarski, 2021 ). Fear of COVID-19 further results in multiple complications, including emotional arousal (Islam et al, 2021 ), fear of spreading the virus to other people (Vagni et al, 2020 ), psychological reactance (Akhtar et al, 2020 ), xenophobia (Mamun and Griffiths, 2020 ; Ahuja et al, 2021 ), intolerance and uncertainty (Satici et al, 2020b ), depression, anxiety and stress (Bakioglu et al, 2021 ; Pan et al, 2021 ), and secondary trauma (Khattak et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Fear of COVID-19 and secondary trauma: Moderating role of self-efficacy

Abbas

Manthar

et al. 2022

Front. Psychol.

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COVID-19 has affected millions of people around the globe. People's mental health, especially those of nurses, has been primarily affected by the fear of this virus. More focus has been paid to vaccination and treatment of the virus, but less attestation has been given to addressing the mental health of people affected by the virus. Empirical studies show that different external factors are not easily manageable and controllable by the individual. This study preliminarily explores the connection between fear of COVID-19 and secondary traumatic stress in nurses. Further, it examines the moderating effects of occupational self-efficacy on the relationship between fear of COVID-19 and secondary traumatic stress. Data for the study was collected from the nurses of six large hospitals in Karachi, Pakistan. The final analysis was performed on 243 samples. Studies on COVID-19 suggest that increased occupational self-efficacy decreases fear and its impact. This study offers insights for managers to develop stress management programs and provide proper training and counseling sessions to the nurses to motivate them emotionally. Theoretically, this study broadens the understanding of the theory of emotions by using the pandemic as a stressor. Future studies may explore different roles of occupational self-efficacy and study its influential role in managing different kinds of emotions explained by the theory of emotions. Managers at the workplace could design different self-efficacy training for nurses to increase their self-motivation to fight different types of stress they face at the workplace.

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Neuroinflammation as a pathophysiological factor in the development and maintenance of functional seizures: A hypothesis

Cited by 15 publications

References 88 publications

Decreased uncinate fasciculus integrity in functional seizures following traumatic brain injury

Decreased uncinate fasciculus integrity in functional seizures following traumatic brain injury

Cortisol and α-amylase awakening response in children and adolescents with functional neurological (conversion) disorder

Fear of COVID-19 and secondary trauma: Moderating role of self-efficacy

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