One-year follow-up of neurobehavioral therapy in functional seizures or epilepsy with traumatic brain injury: A nonrandomized controlled trial.

OBJECTIVE: Patients with traumatic brain injury (TBI) often present with seizures (functional and/or epileptic), but treatments for patients with TBI and seizures are limited. We examined treatment phase and 1-year post-enrollment outcomes following neurobehavioral therapy (NBT) for patients with TBI + functional seizures (FS) and TBI + epilepsy. METHODS: In this multicenter, prospective, three-group, nonrandomized, controlled trial, with 1-year post-enrollment follow-up, three cohorts of adults were recruited: TBI + video-electroencephalography (EEG)-confirmed FS (n = 89), TBI + EEG-confirmed epilepsy (n = 29), and chart/history-confirmed TBI without seizures (n = 75). Exclusion criteria were recent psychotic or self-injurious behavior, current suicidal ideation, pending litigation or long-term disability, active substance use disorder, and inability to participate in study procedures. TBI + FS and TBI + epilepsy groups completed NBT for seizures, an evidence-based, 12-session, multimodal psychotherapy, whereas TBI without seizures participants received standard medical care. The primary outcome was change in seizure frequency; secondary outcomes were changes in mental health, TBI-related symptoms, disability, and quality of life. RESULTS: Reductions in average monthly seizures occurred during treatment in TBI + FS participants (p = .002) and were significant from baseline (mean = 16.75; 95% confidence interval [CI] = 11.44-24.53) to 12 months post-enrollment (mean = 7.28, 95% CI = 4.37-12.13, p = .002, d = .38). Monthly seizures decreased during treatment in TBI + epilepsy participants (p = .002); reductions were not statistically significant from baseline (mean = 2.38, 95% CI = 1.12-5.04) to 12-month postenrollment (mean = .98, 95% CI = .40-2.42, p = .07, d = .22). Regarding treatment-phase changes in secondary outcome measures, TBI + FS participants improved significantly on 10 of 19 variables (52.6%), TBI + epilepsy participants improved on five of 19 (26.3%), and TBI-only comparisons improved on only one of 19 (5.3%). SIGNIFICANCE: NBT benefited patients with TBI + FS and TBI + epilepsy. Improvements were demonstrated at 1 year post-enrollment in those with TBI + FS. NBT may be a clinically useful treatment for patients with seizures.

Reduced Subjective Cognitive Concerns With Neurobehavioral Therapy in Functional Seizures and Traumatic Brain Injury.

OBJECTIVE: Functional seizures are common among people with traumatic brain injury (TBI). Subjective cognitive concerns refer to a person's own perception of problems with cognitive functioning in everyday life. The authors investigated the presence and correlates of subjective cognitive concerns and the response to neurobehavioral therapy among adults with TBI and functional seizures (TBI+FS group). METHODS: In this observational study, participants in the TBI+FS group (N=47) completed a 12-session neurobehavioral therapy protocol for seizures, while participants in the comparison group (TBI without seizures) (N=50) received usual treatment. Subjective cognitive concerns, objective cognition, mental health, and quality of life were assessed before and after treatment. Data collection occurred from 2018 to 2022. RESULTS: Baseline subjective cognitive concerns were reported for 37 (79%) participants in the TBI+FS group and 20 (40%) participants in the comparison group. In a multivariable regression model in the TBI+FS group, baseline global mental health (ß=-0.97) and obsessive-compulsive symptoms (ß=-1.01) were associated with subjective cognitive concerns at baseline. The TBI+FS group had fewer subjective cognitive concerns after treatment (η2=0.09), whereas the TBI comparison group showed a nonsignificant increase in subjective cognitive concerns. CONCLUSIONS: Subjective cognitive concerns are common among people with TBI and functional seizures and may be related to general mental health and obsessive-compulsive symptoms. Evidence-based neurobehavioral therapy for functional seizures is a reasonable treatment option to address such concerns in this population, although additional studies in culturally diverse samples are needed. In addition, people with functional seizures would likely benefit from rehabilitation specifically targeted toward cognitive functioning.

Relationship between neural responses to stress and mental health symptoms in psychogenic nonepileptic seizures after traumatic brain injury.

OBJECTIVE: To utilize traumatic brain injury (TBI) as a model for investigating functioning during acute stress experiences in psychogenic nonepileptic seizures (PNES) and to identify neural mechanisms underlying the link between changes in processing of stressful experiences and mental health symptoms in PNES. METHODS: We recruited 94 participants: 50 with TBI only (TBI-only) and 44 with TBI and PNES (TBI + PNES). Participants completed mood (Beck Depression Inventory-II), anxiety (Beck Anxiety Inventory), and posttraumatic stress disorder (PTSD) symptom (PTSD Checklist-Specific Event) assessments before undergoing functional magnetic resonance imaging during an acute psychosocial stress task. Linear mixed-effects analyses identified clusters of significant interactions between group and neural responses to stressful math performance and stressful auditory feedback conditions within limbic brain regions (volume-corrected α = .05). Spearman rank correlation tests compared mean cluster signals to symptom assessments (false discovery rate-corrected α = .05). RESULTS: Demographic and TBI-related measures were similar between groups; TBI + PNES demonstrated worse clinical symptom severity compared to TBI-only. Stressful math performance induced relatively greater reactivity within dorsomedial prefrontal cortex (PFC) and right hippocampal regions and relatively reduced reactivity within left hippocampal and dorsolateral PFC regions for TBI + PNES compared to TBI-only. Stressful auditory feedback induced relatively reduced reactivity within ventral PFC, cingulate, hippocampal, and amygdala regions for TBI + PNES compared to TBI-only. Changes in responses to stressful math within hippocampal and dorsal PFC regions were correlated with increased mood, anxiety, and PTSD symptom severity. SIGNIFICANCE: Corticolimbic functions underlying processing of stressful experiences differ between patients with TBI + PNES and those with TBI-only. Relationships between these neural responses and symptom assessments suggest potential pathophysiologic mechanisms in PNES.

A pilot study of stellate ganglion block paired with exposure therapy: Feasibility and acceptability in combat veterans with posttraumatic stress disorder.

BACKGROUND: There is growing evidence that stellate ganglion block (SGB) combined with trauma-focused therapy may help veterans with posttraumatic stress disorder (PTSD) whose symptoms have not responded to traditional treatments. By combining SGB with in vivo exposure, veterans may be more able to fully engage in treatment and see improvement in their overall functioning. OBJECTIVE: The primary aim of this project was to conduct a nonrandomized pilot trial on the feasibility and acceptability of delivering SGB paired with individual psychotherapy to veterans with combat-related PTSD. METHOD: Eligible veterans (N = 14) constructed a hierarchy of in vivo exposure exercises, received the SGB procedure, and attended four additional weekly psychotherapy sessions with a focus on exposure exercises. Participants completed measures at baseline, weekly during treatment, and follow-up assessments immediately posttreatment and 1-month later. RESULTS: The recruitment target was easily met, session attendance was strong, and dropout was relatively low (21.4%). SGB was well tolerated with only mild, transient side effects. Participants reported satisfaction with the treatment they received as measured by the Client Satisfaction Questionnaire (M = 28.8). Paired t test analyses revealed a significant decrease in PTSD symptoms as measured by the PTSD Checklist for DSM-5. We also observed a significant reduction in PTSD symptoms as measured by the Clinician-Administered PTSD Scale for DSM-5 in mixed models, F(2, 13) = 8.68, p = .004. There were no significant improvements in psychosocial functioning or quality of life. CONCLUSION: SGB paired with psychotherapy is feasible and acceptable to veterans and holds promise for symptom reduction among veterans with combat-related PTSD. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Clinician-rated outcomes of patients with functional neurological disorders treated in an outpatient clinic.

BACKGROUND: Patients with functional neurological (conversion) disorder (FND) have historically been difficult to treat. Outcomes have been studied in research trials, documenting improvements; however, limited information is available from a community-treated FND cohort. OBJECTIVES: We aimed to examine clinical outcomes in outpatients with FND treated with the Neuro-Behavioral Therapy (NBT) approach. These uncontrolled setting treatment data could complement more structured clinical studies results. METHODS: We conducted a retrospective chart review of consecutive patients diagnosed with FND, ages 17 to 75, who were treated with the NBT workbook at the Rhode Island Hospital Behavioral Health clinic between 2014 and 2022. NBT consisted of 45-minute, individual, outpatient sessions, in clinic or via telehealth with one clinician. Global Assessment of Functioning (GAF), and Clinical Global Impression (CGI) -Severity, and -Improvement were scored for every appointment. RESULTS: Baseline characteristics are available for 107 patients. Mean age at FND symptom onset was 37 years. Patients had a mix of FND semiologies, which included Psychogenic Nonepileptic Seizures (71%), Functional Movement Disorder (24.3%), Functional Sensory Disorder (14%), Functional Weakness (6.5%), and Functional Speech Disorder (5.6%). Clinical evaluation scores revealed improvements over time. CONCLUSIONS: We describe a well-characterized sample of patients with various and mixed FND semiologies, who received manualized therapy, NBT, in an outpatient clinic. Patients had similar psychosocial profiles to those in clinical studies and displayed improvement in clinical measures. These results demonstrate the practicability of NBT for motor FND semiologies and for PNES, in a "real-world" outpatient practice, extending care beyond structured clinical trials.

Improvements in Montreal Cognitive Assessment scores after neurobehavioral therapy in adults with functional (nonepileptic) seizures and traumatic brain injury.

Cognitive functioning impacts clinical symptoms, treatment response, and quality of life in adults with functional/nonepileptic seizures (FS/NES), but no study to date examines effects of behavioral FS/NES treatment on cognition in these patients. We hypothesized that there would be a reduction in cognitive symptoms in participants with FS/NES and traumatic brain injury (TBI) following neurobehavioral therapy (NBT). We also hypothesized that select seizure-related, medication, subjective cognitive, and mental health symptoms would be negatively correlated with improvements in cognitive performance after NBT. Participants were 37 adults with TBI + FS/NES and 35 adults with TBI only, recruited from medical centers in the northeastern or southeastern U.S. TBI + FS/NES participants completed a 12 session NBT intervention, and TBI without seizures participants were not treated. All participants completed pre-post assessments of cognition (Montreal Cognitive Assessment [MoCA]) and baseline sociodemographic factors and mental health symptoms. Pre-post MoCA scores increased significantly in TBI + FS/NES participants (28/37 [75.7%] improved) but not in TBI comparisons (10/35 [28.6%] improved). Language, memory, and visuospatial/executive functions, but not attention, improved over time in the TBI + FS/NES group. Gains in cognition were concentrated in those TBI + FS/NES participants with likely baseline cognitive impairments (MoCA total score <26), and 9/17 of these participants moved from the "impaired" range at baseline (<26) to the "intact" range at endpoint (≥26). Lastly, participants taking fewer medications and reporting lower subjective cognitive difficulties at baseline showed larger pre-post MoCA total score improvements. Overall, results from this study suggest the potential for positive change in cognition in FS/NES and co-occurring TBI using evidence-based psychotherapy.

White matter and neurite morphology differ in psychogenic nonepileptic seizures.

OBJECTIVE: To further evaluate the relationship between the clinical profiles and limbic and motor brain regions and their connecting pathways in psychogenic nonepileptic seizures (PNES). Neurite Orientation Dispersion and Density Indices (NODDI) multicompartment modeling was used to test the relationships between tissue alterations in patients with traumatic brain injury (TBI) and multiple psychiatric symptoms. METHODS: The sample included participants with prior TBI (TBI; N = 37) but no PNES, and with TBI and PNES (TBI + PNES; N = 34). Participants completed 3T Siemens Prisma MRI high angular resolution imaging diffusion protocol. Statistical maps, including fractional anisotropy (FA), mean diffusivity (MD), neurite dispersion [orientation dispersion index (ODI)] and density [intracellular volume fraction (ICVF), and free water (i.e., isotropic) volume fraction (V-ISO)] signal intensity, were generated for each participant. Linear mixed-effects models identified clusters of between-group differences in indices of white matter changes. Pearson's r correlation tests assessed any relationship between signal intensity and psychiatric symptoms. RESULTS: Compared to TBI, TBI + PNES revealed decreases in FA, ICVF, and V-ISO and increases in MD for clusters within cingulum bundle, uncinate fasciculus, fornix/stria terminalis, and corticospinal tract pathways (cluster threshold α = 0.05). Indices of white matter changes for these clusters correlated with depressive, anxiety, PTSD, psychoticism, and somatization symptom severity (FDR threshold α = 0.05). A follow-up within-group analysis revealed that these correlations failed to reach the criteria for significance in the TBI + PNES group alone. INTERPRETATION: The results expand support for the hypothesis that alterations in pathways comprising the specific PNES network correspond to patient profiles. These findings implicate myelin-specific changes as possible contributors to PNES, thus introducing novel potential treatment targets.