Emotion processing and metacognition in patients with dissociative seizures

Dissoziative Anfälle sind kurze Episoden psychologischen Ursprungs, die Veränderungen des Bewusstseins und der Verhaltenskontrolle beinhalten. In dieser Dissertation werden Emotionsverarbeitung und metakognitive Funktionen bei Patienten mit dissoziativen Anfällen mit Hilfe eines experimentell-behavioralen Ansatzes, Selbstberichtsfragebögen und hochqualitativer Diffusionstensor-Bildgebung untersucht. Wir konnten Beeinträchtigungen der Emotionsverarbeitung bei Patienten mit dissoziativen Anfällen nachweisen, die mit der mikrostrukturellen Integrität distinkter Hirnnetzwerke korreliert waren. Die mikrostrukturelle Integrität dieser Netzwerke war zudem sowohl mit traumatischen Erfahrungen als auch mit der klinischen Manifestation der Störung korreliert. Diese Befunde ermöglichen ein detaillierteres Wissen über wichtige pathomechanische Faktoren und könnten Wissenschaftlern, Klinikern und betroffenen Patienten ein tieferes Verständnis dieser beeinträchtigenden Erkrankung ermöglichen.Dissociative seizures are brief episodes of altered awareness and behavioural control which are assumed to be of psychological origin. In this dissertation, emotion processing and metacognitive functions in patients with dissociative seizures are investigated using an experimental-behavioural approach, self-report questionnaires, and high-quality diffusion tensor imaging. We found impairments in emotion processing in patients with dissociative seizures, which were correlated with the microstructural integrity of distinctive brain networks. The microstructural integrity of these networks was furthermore related both to traumatic experiences and to the clinical manifestation of the disorder. These findings and their comprehensive integration across multiple levels provide a more detailed knowledge on key pathomechanistic factors and might enable scientists, clinicians, and affected patients to gain a deeper understanding of this debilitating illness

Locus coeruleus co-activation patterns at rest show higher state persistence in patients with dissociative seizures: A pilot study

Objective. Dissociative seizures are paroxysmal disruptions of awareness and behavioural control in the context of affective arousal. Alterations in stress-related endocrine function have been demonstrated, but the timescale of dissociation suggests that the central locus coeruleus (LC) noradrenergic system is likely pivotal. Here, we investigate whether LC activation at rest is associated with altered brain network dynamics. Methods. A preliminary co-activation pattern (CAP) analysis of resting-state functional magnetic resonance imaging (fMRI) in 14 patients with dissociative seizures and 14 healthy controls was performed by using the LC as a seeding region. The red nucleus served as a control condition. Entry rates, durations as well as state transition probabilities of identified CAPs were calculated. Analyses were corrected for demographic, technical, and clinical confounders including depression and anxiety. Results. Three LC-related CAPs were identified, with the dominant two showing inverse activations and deactivations of the default mode network and the attention networks, respectively. Analysis of transition probabilities between and within the three CAPs revealed higher state persistence in patients compared to healthy controls for both CAP2LC (Cohen’s d=-0.55; p=0.01) and CAP3LC (Cohen’s d=-0.57; p=0.01). The control analysis using the red nucleus as a seed yielded similar CAPs, but no significant between-group differences in transition probabilities. Significance. Higher state persistence of LC-CAPs in patients with dissociative seizures generates the novel hypothesis that arousal-related impairments of network switching might be a candidate neural mechanism of dissociation

Cognitive performance in functional neurological disorder: A systematic review and meta-analysis

Background: Cognitive complaints are common in functional neurological disorder (FND), but it is unclear whether objective neurocognitive deficits are present. This systematic review summarised validated/standardised cognitive test performance in FND samples across cognitive domains. Methods: Embase, PsycInfo and MEDLINE were searched from inception to 15th May 2023, combining terms for FND and cognitive domains (e.g., attention, memory, executive functioning). Studies included a range of FND phenotypes (seizures, motor, cognitive disorder, mixed), compared to healthy or clinical controls. Risk of bias was assessed with the modified Newcastle-Ottawa Scale and a qualitative synthesis/narrative review of cognitive performance in FND was conducted. Test performance scores were extracted, and random-effects meta-analyses were run where appropriate. This review was registered on PROSPERO, CRD42023423139. Results: Fifty-six studies including2260 individuals with FND were eligible. Although evidence for some impairments emerged across domains of executive functioning, attention, memory, and psychomotor/processing speed, this was inconsistent across studies and FND phenotypes. Common confounds included group differences in demographics, medication, and intellectual functioning. Only 24% of studies objectively assessed performance validity. Meta-analyses revealed higher scores on tests of naming (g=.67, 95%CI [.50, .84]) and long-term memory (g=.43, 95%CI [.13, .74]) in functional seizures versus epilepsy, but no significant differences in working (g=-.08, 95%CI [-.44, .29]) or immediate (g=.25, 95%CI [-.02, .53]) memory and cognitive flexibility (g=-.01, 95%CI [-.29, .28]). Conclusions: There is mixed evidence for objective cognitive deficits in FND. Future research should control for confounds, include tests of performance validity, and assess relationships between objective and subjective neurocognitive functioning

Cortical thickness in default mode network hubs correlates with clinical features of dissociative seizures

BACKGROUND: Dissociative seizures (DS) are a common subtype of functional neurological disorder (FND) with an incompletely understood pathophysiology. Here, gray matter variations and their relationship to clinical features were investigated. METHODS: Forty-eight patients with DS without neurological comorbidities and 43 matched clinical control patients with syncope with structural brain MRIs were identified retrospectively. FreeSurfer-based cortical thickness and FSL FIRST-based subcortical volumes were used for quantitative analyses, and all findings were age and sex adjusted, and corrected for multiple comparisons. RESULTS: Groups were not statistically different in cortical thickness or subcortical volumes. For patients with DS, illness duration was inversely correlated with cortical thickness of left-sided anterior and posterior cortical midline structures (perigenual/dorsal anterior cingulate cortex, superior parietal cortex, precuneus), and clusters at the left temporoparietal junction (supramarginal gyrus, postcentral gyrus, superior temporal gyrus), left postcentral gyrus, and right pericalcarine cortex. Dissociative seizure duration was inversely correlated with cortical thickness in the left perigenual anterior cingulate cortex, superior/middle frontal gyri, precentral gyrus and lateral occipital cortex, along with the right isthmus-cingulate and posterior-cingulate, middle temporal gyrus, and precuneus. Seizure frequency did not show any significant correlations. CONCLUSIONS: In patients with DS, illness duration inversely correlated with cortical thickness of left-sided default mode network cortical hubs, while seizure duration correlated with left frontopolar and right posteromedial areas, among others. Etiological factors contributing to neuroanatomical variations in areas related to self-referential processing in patients with DS require more research inquiry

Cortical thickness in default mode network hubs correlates with clinical features of dissociative seizures

BACKGROUND: Dissociative seizures (DS) are a common subtype of functional neurological disorder (FND) with an incompletely understood pathophysiology. Here, gray matter variations and their relationship to clinical features were investigated. METHODS: Forty-eight patients with DS without neurological comorbidities and 43 matched clinical control patients with syncope with structural brain MRIs were identified retrospectively. FreeSurfer-based cortical thickness and FSL FIRST-based subcortical volumes were used for quantitative analyses, and all findings were age and sex adjusted, and corrected for multiple comparisons. RESULTS: Groups were not statistically different in cortical thickness or subcortical volumes. For patients with DS, illness duration was inversely correlated with cortical thickness of left-sided anterior and posterior cortical midline structures (perigenual/dorsal anterior cingulate cortex, superior parietal cortex, precuneus), and clusters at the left temporoparietal junction (supramarginal gyrus, postcentral gyrus, superior temporal gyrus), left postcentral gyrus, and right pericalcarine cortex. Dissociative seizure duration was inversely correlated with cortical thickness in the left perigenual anterior cingulate cortex, superior/middle frontal gyri, precentral gyrus and lateral occipital cortex, along with the right isthmus-cingulate and posterior-cingulate, middle temporal gyrus, and precuneus. Seizure frequency did not show any significant correlations. CONCLUSIONS: In patients with DS, illness duration inversely correlated with cortical thickness of left-sided default mode network cortical hubs, while seizure duration correlated with left frontopolar and right posteromedial areas, among others. Etiological factors contributing to neuroanatomical variations in areas related to self-referential processing in patients with DS require more research inquiry

Diagnostic challenges in patients with temporal lobe seizures and features of autoimmune limbic encephalitis

Ismail FS, Spatola M, Wörmann FG, et al. Diagnostic challenges in patients with temporal lobe seizures and features of autoimmune limbic encephalitis. European journal of neurology. Accepted.BACKGROUND: Consensus criteria for autoimmune limbic encephalitis (ALE) allow for a diagnosis even without neural antibodies (Abs), but it remains unclear which clinical features should prompt neural Ab screening in temporal lobe epilepsy patients.; METHODS: We identified 47 patients from a tertiary epilepsy center with mediotemporal lobe seizures and additional features suggestive of limbic involvement, including either memory deficits, psychiatric symptoms, mediotemporal MRI hyperintensities or inflammatory CSF. Neuronal Ab testing was carried out at two independent reference laboratories (Bielefeld-Bethel, Germany, and Barcelona, Spain). All brain MRIs were assessed by two reviewers independently.; RESULTS: Temporal lobe seizures were accompanied by memory deficits in 35/46 (76%), by psychiatric symptoms in 27/42 (64%), and by both in 19/42 (45%). Limbic T2/FLAIR signal hyperintensities were found in 26/46 (57%) patients (unilateral n = 22, bilateral n = 4). Standard CSF studies were abnormal in 2/37 (5%). Neuronal Abs were confirmed in serum and/or CSF in 8/47 (17%) cases and were directed against neuronal cell-surface targets (LGI1 n = 1, CASPR2 n = 1, undetermined target n = 3) or GAD65 (n = 3, all with high titers). Compared to Ab-negative patients, those who harbored neuronal Abs were more likely to have uni- or bilateral mediotemporal MRI changes (8/8, 100% versus 18/38, 47%, p=0.01, Fisher exact test).; CONCLUSIONS: In patients with temporal lobe seizures and additional limbic signs, 17% had neuronal Abs affirming ALE diagnosis. Mediotemporal MRI changes were found in all Ab-positive cases and had a positive likelihood ratio of 2.11 (95% CI 1.51 - 2.95). This article is protected by copyright. All rights reserved

Suggestive seizure induction for inpatients with suspected psychogenic nonepileptic seizures

$\bf Objective$ To determine the utility of suggestive seizure induction for inpatient work-up of suspected psychogenic nonepileptic seizures (PNES). $\bf Methods$ Prospective study of epilepsy center inpatient admissions with suspected PNES. Patients were randomized to undergo suggestive induction first (group A) and then, if necessary, long-term video-electroencephalography (EEG) monitoring, or vice versa (group B). Diagnostic pathways were compared. Potential clinical predictors for diagnostic success were evaluated. $\bf Results$ Length of in-hospital stay did not significantly differ between groups. Suspicion of PNES was confirmed in 43 of 77 (56%) patients, evenly distributed between group A (22 of 39) and group B (21 of 38). In nine patients, recorded habitual seizures were epileptic and in 25 cases, no diagnostic event could be recorded. Diagnosis of PNES was ascertained primarily by recording a typical seizure through suggestive induction in 24 patients and through long-term monitoring in 19 patients. In group A (induction first), monitoring was not deemed necessary in 21% of cases. In group B (monitoring first), 13% would have remained inconclusive without suggestive induction. Patients who reported triggers to their habitual seizures were not more likely to have spontaneous or provoked PNES during monitoring or suggestive inducion, respectively. Patients with subjective seizure prodromes (auras) were significantly more likely to have a PNES during suggestive induction than those without (odds ratio [OR] 3.4, 95% confidence interval [CI] 1.1-10.4). There was no significant difference in seizure frequency between patients with spontaneous PNES during long-term monitoring and those with nondiagnostic monitoring sessions. $\bf Significance$ Our results support the notion that suggestive seizure induction can reduce the number of inconclusive inpatient workups, and can obviate resource-intensive long-term monitoring in one fifth of cases. Patients who are aware of prodromes might have a higher chance of having seizures induced through suggestion

Point-of-care testing using a neuropsychology pocketcard set

Neurocognitive screening instruments usually require printed sheets and additional accessories, and can be unsuitable for low-threshold use during ward rounds or emergency workup, especially in patients with motor impairments. Here, we test the utility of a newly developed neuropsychology pocketcard set for point-of-care testing. For aphasia and neglect assessment, modified versions of the Language Screening Test and the Bells Test were validated on 63 and 60 acute stroke unit patients, respectively, against expert clinical evaluation and the original pen-and-paper Bells Test. The pocketcard aphasia test achieved an excellent area under the curve (AUC) of 0.94 (95% CI: 0.88–1, $\it p$ < 0.001). Using an optimal cut-off of $\geq$2 mistakes, sensitivity was 91% and specificity was 81%. The pocketcard Bells Task, measured against the clinical neglect diagnosis, achieved higher sensitivity (89%) and specificity (88%) than the original paper-based instrument (78% and 75%, respectively). Separately, executive function tests (modified versions of the Trail Making Test [TMT] A and B, custom Stroop color naming task, vigilance 'A' Montreal Cognitive Assessment item) were validated on 44 inpatients with epilepsy against the EpiTrack® test battery. Pocketcard TMT performance was significantly correlated with the original EpiTrack® versions (A: $\it r$ = 0.64, $\it p$ < 0.001; B: $\it r$ = 0.75, $\it p$ < 0.001). AUCs for the custom Stroop task, TMT A and TMT B for discriminating between normal and pathological EpiTrack® scores were acceptable, excellent and outstanding, respectively. Quick point-of-care testing using a pocketcard set is feasible and yields diagnostically valid information