OBJECTIVE: Apathy and depression are both common after moderate to severe traumatic brain injury (TBI) and may be especially important to distinguish in older adults with TBI. The authors examined apathy and depression i...OBJECTIVE: Apathy and depression are both common after moderate to severe traumatic brain injury (TBI) and may be especially important to distinguish in older adults with TBI. The authors examined apathy and depression in relation to cognitive performance domains and their potentially unique contribution to psychosocial functioning in this patient population. METHODS: A total of 106 participants (mean±SD age=64±8 years) with chronic moderate to severe TBI (≥1 year) completed questionnaires assessing severity of apathy (Frontal Systems Behavior Scale-apathy subscale) and depression (Geriatric Depression Scale-15) symptoms, health-related quality of life (HRQoL), and societal participation. Participants also completed neuropsychological tests of episodic memory, processing speed, and executive functioning. RESULTS: Apathy symptom severity was significantly associated with all cognitive performances in correlations adjusted for the familywise error rate; a relationship with executive functioning remained after controlling for demographic and injury variables. Depression symptom severity was not significantly associated with cognition after statistical correction. Both symptomatologies uniquely contributed to HRQoL. Only depression symptoms contributed to societal participation. On the basis of clinical cutoffs, half the sample had neither depression nor apathy, approximately 25% met criteria for only apathy, and 25% had both apathy and depression. The combined presence of clinical depression and apathy was associated with worse HRQoL and societal participation. CONCLUSIONS: This is the first study to examine apathy and depression in relation to cognition and psychosocial functioning in an older sample with a history of TBI. Findings suggest that the two syndromes can be dissociated in clinically meaningful ways, which may help to refine psychiatric and behavioral interventions in this vulnerable population.
Luccarelli J, Smith JR, Fricchione G
… +1 more, Westover MB
J Neuropsychiatry Clin Neurosci
· 2024 · PMID 38720623
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OBJECTIVE: Generalized periodic discharges are a repeated and generalized electroencephalography (EEG) pattern that can be seen in the context of altered mental status. This article describes a series of five individuals...OBJECTIVE: Generalized periodic discharges are a repeated and generalized electroencephalography (EEG) pattern that can be seen in the context of altered mental status. This article describes a series of five individuals with generalized periodic discharges who demonstrated signs and symptoms of catatonia, a treatable neuropsychiatric condition. METHODS: Inpatients with a clinical diagnosis of catatonia, determined with the Bush-Francis Catatonia Rating Scale (BFCRS), and EEG recordings with generalized periodic discharges were analyzed in a retrospective case series. RESULTS: Five patients with catatonia and generalized periodic discharges on EEG were evaluated from among 106 patients with catatonia and contemporaneous EEG measurements. Four of these patients showed an improvement in catatonia severity when treated with benzodiazepines, with an average reduction of 6.75 points on the BFCRS. CONCLUSIONS: Among patients with generalized periodic discharges, catatonia should be considered, in the appropriate clinical context. Patients with generalized periodic discharges and catatonia may benefit from treatment with empiric trials of benzodiazepines.
OBJECTIVE: Although a majority of individuals recover from a concussion within weeks of the index injury, a substantial minority of patients report persistent postconcussion symptoms. Some of these symptoms may reflect a...OBJECTIVE: Although a majority of individuals recover from a concussion within weeks of the index injury, a substantial minority of patients report persistent postconcussion symptoms. Some of these symptoms may reflect a diagnosis of functional neurological disorder (FND). The authors evaluated the relationship between persistent postconcussion symptoms and FND symptoms. METHODS: In this retrospective chart review, the authors characterized demographic and clinical information from 50 patients with a confirmed diagnosis of FND whose functional neurological symptoms started after a concussion. RESULTS: Patients who developed FND after a concussion had high rates of baseline risk factors for both persistent postconcussion symptoms and FND. After the concussive event, functional neurological symptoms presented abruptly or developed insidiously over time. Functional neurological symptoms ranged widely and included gait symptoms, seizures, speech and language symptoms, weakness, sensory symptoms, tremors, and vision and oculomotor symptoms. CONCLUSIONS: Functional neurological symptoms can arise after a concussion. FND should be considered in the differential diagnosis of individuals presenting with neurological symptoms beginning after a concussion. By failing to recognize functional symptoms, clinicians may inadvertently reinforce negative health-related beliefs regarding a patient's injured brain.
Jones MB, Tea J, Meyers M
… +4 more, Li R, Villalon A, Agrawal R, Jorge RE
J Neuropsychiatry Clin Neurosci
· 2024 · PMID 38650465
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OBJECTIVE: Posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI), which are prevalent conditions among post-9/11 veterans, increase risks of rapid eye movement (REM) sleep behavior disorder (RBD) and dege...OBJECTIVE: Posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI), which are prevalent conditions among post-9/11 veterans, increase risks of rapid eye movement (REM) sleep behavior disorder (RBD) and degenerative synucleinopathy. Rates and predictors of RBD symptoms were investigated by screening post-9/11 veterans for RBD with a validated questionnaire. METHODS: In this cross-sectional analysis, consecutive patients in the Houston Translational Research Center for TBI and Stress Disorders (TRACTS) were screened with the English translation of the RBD Questionnaire-Hong Kong (RBDQ-HK). In addition to data from the standard TRACTS battery, systematic chart review was used to identify known sleep disorders mimicking or manifesting RBD. RESULTS: Of the 119 patients with available RBDQ-HK scores, 71 (60%) and 65 (55%) screened positive for RBD, when a total score ≥21 and a factor 2 score ≥8 were used as cutoff scores, respectively. Univariable analyses with both cutoffs showed consistent associations between a positive RBDQ-HK screen and global sleep quality, number of TBI exposures, and PTSD severity. Multivariable logistic regression with total score ≥21 as a cutoff indicated that PTSD severity (odds ratio=1.06, 95% CI=1.02-1.10) and number of TBIs (odds ratio=1.63, 95% CI=1.16-2.41) were independent predictors of a positive screen, whereas global sleep quality was no longer significant. Multivariable logistic regression with factor 2 score ≥8 as a cutoff showed similar results. CONCLUSIONS: Interdisciplinary parasomnia assessment, further validation of RBD screens, and standardized reporting of REM sleep without atonia could provide necessary information on the pathophysiological relationships linking PTSD, TBI, RBD symptoms, and ultimately synucleinopathy risk among post-9/11 veterans.
OBJECTIVE: Emotional and behavioral dyscontrol (EBD), a neuropsychiatric complication of stroke, leads to patient and caregiver distress and challenges to rehabilitation. Studies of neuropsychiatric sequelae in stroke ar...OBJECTIVE: Emotional and behavioral dyscontrol (EBD), a neuropsychiatric complication of stroke, leads to patient and caregiver distress and challenges to rehabilitation. Studies of neuropsychiatric sequelae in stroke are heavily weighted toward ischemic stroke. This study was designed to compare risk of EBD following intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) and to identify risk factors for EBD following hemorrhagic stroke. METHODS: The authors conducted a prospective cohort study of patients hospitalized for nontraumatic hemorrhagic stroke between 2015 and 2021. Patients or legally authorized representatives completed the Quality of Life in Neurological Disorders (Neuro-QOL) EBD short-form inventory 3 months after hospitalization. Univariable and multivariable analyses identified risk factors for EBD after hemorrhagic stroke. RESULTS: The incidence of EBD was 21% (N=15 of 72 patients) at 3 months after hemorrhagic stroke. Patients with ICH were more likely to develop EBD; 93% of patients with EBD (N=14 of 15) had ICH compared with 56% of patients without EBD (N=32 of 57). The median Glasgow Coma Scale (GCS) score at hospital admission was lower among patients who developed EBD (13 vs. 15 among those without EBD). Similarly, admission scores on the National Institutes of Health Stroke Scale (NIHSS) and the Acute Physiology and Chronic Health Evaluation II (APACHE II) were higher among patients with EBD (median NIHSS score: 7 vs. 2; median APACHE II score: 17 vs. 11). Multivariable analyses identified hemorrhage type (ICH) and poor admission GCS score as predictors of EBD 3 months after hemorrhagic stroke. CONCLUSIONS: Patients with ICH and a low GCS score at admission are at increased risk of developing EBD 3 months after hemorrhagic stroke and may benefit from early intervention.
Depression is a common psychiatric disorder among individuals with Huntington's disease (HD). Depression in HD and major depressive disorder appear to have different pathophysiological mechanisms. Despite the unique path...Depression is a common psychiatric disorder among individuals with Huntington's disease (HD). Depression in HD and major depressive disorder appear to have different pathophysiological mechanisms. Despite the unique pathophysiology, the treatment of depression in HD is based on data from the treatment of major depressive disorder in the general population. The objective of this systematic review was to conduct a comprehensive evaluation of the available evidence. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Studies on the treatment of depression in HD were identified by searching MEDLINE, Embase, and PsycInfo. The initial search yielded 2,771 records, 41 of which were ultimately included. There were 19 case reports, seven case series, three cross-sectional studies, one qualitative study, nine nonrandomized studies, and two randomized trials among the included studies. The most common assessment tools were the Hospital Anxiety and Depression Scale (N=8), the Beck Depression Inventory (N=6), and the Hamilton Depression Rating Scale (N=6). Only 59% of the included studies assessed depressive symptoms with a scoring system. The pharmacological options for the treatment of depression included antidepressants and antipsychotics. Nonpharmacological approaches were multidisciplinary rehabilitation, psychotherapy, and neurostimulation. Limited evidence on the treatment of depression in HD was available, and this literature consisted mainly of case reports and case series. This systematic review highlights the knowledge gap and the pressing need for HD-specific research to determine the efficacy of treatment approaches for depression in HD.
OBJECTIVE: A considerable number of people experience persisting symptoms and functional limitations after mild traumatic brain injury (mTBI). It is unclear whether subtle white matter changes contribute to this phenomen...OBJECTIVE: A considerable number of people experience persisting symptoms and functional limitations after mild traumatic brain injury (mTBI). It is unclear whether subtle white matter changes contribute to this phenomenon. In this systematic review, the authors evaluated whether microstructural white matter indices on advanced MRI are related to clinical dysfunction among patients without abnormalities on standard brain computed tomography (CT) or MRI (uncomplicated mTBI). METHODS: A search of multiple databases was performed. Studies with individuals who experienced blast-related, sports-related, or multiple mTBIs were excluded. Diffusion tensor imaging (DTI) and susceptibility-weighted imaging (SWI) metrics and cognitive, neuropsychiatric, or functional outcome measures were extracted from each study. RESULTS: Thirteen studies were selected (participants with mTBI, N=553; healthy control group, N=438). Seven DTI studies evaluated cognitive function, with five reporting significant correlations between reduced white matter integrity and deficits in attention, processing speed, and executive function at 6-12 months after injury (three studies included only individuals with uncomplicated mTBI). Four studies found significant correlations between DTI metrics and persistent postconcussive symptoms after 3-12 months (one study included only individuals with uncomplicated mTBI). Two SWI studies reported conflicting findings regarding the relationship between the presence of microbleeds and postconcussive symptoms. CONCLUSIONS: The results revealed that indices of microstructural white matter integrity may relate to clinical presentation 3-12 months after injury in uncomplicated mTBI. However, analysis methods and brain regions studied varied across studies. Further research is needed to identify relationships between white matter indices in specific brain regions and symptom persistence beyond 12 months.
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 auth...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 (β=-0.97) and obsessive-compulsive symptoms (β=-1.01) were associated with subjective cognitive concerns at baseline. The TBI+FS group had fewer subjective cognitive concerns after treatment (η=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.
Millman LSM, Short E, Ward E
… +12 more, Stanton B, Bradley-Westguard A, Goldstein LH, Winston JS, Mehta MA, Nicholson TR, Reinders AATS, David AS, Edwards MJ, Chalder T, Hotopf M, Pick S
OBJECTIVE: This study examined etiological factors and symptom triggers of functional motor symptoms (FMS) or functional seizures (FS) and assessed potential relationships with relevant clinical features (i.e., functiona...OBJECTIVE: This study examined etiological factors and symptom triggers of functional motor symptoms (FMS) or functional seizures (FS) and assessed potential relationships with relevant clinical features (i.e., functional symptoms, quality of life, and general functioning). METHODS: Seventeen participants with FMS or FS and 17 healthy control participants underwent an in-depth clinical interview and completed questionnaires assessing adverse life events, psychological and physical symptoms, alexithymia, autistic traits, illness perceptions, health-related quality of life (HRQoL), and work and social functioning. RESULTS: Participants with FMS or FS perceived various causes of the disorder, including physical symptoms (65%), emotional problems (53%), adverse life events (47%), and work-related factors (29%). Triggers of FMS and FS included physical activity or exertion (59%), stress and emotions (59%), sensory experiences (47%), and fatigue (41%). Compared with healthy control participants, participants with FMS or FS reported more adverse events during adolescence and higher levels of alexithymia, somatoform dissociation, psychological dissociation (disengagement, depersonalization, and derealization), anxiety, depression, and physical symptoms. Participants with FMS or FS had worse HRQoL than healthy control participants and impaired work and social functioning. There were inverse associations between HRQoL scores and somatoform dissociation, anxiety, and adverse life events. CONCLUSIONS: Participants with FMS or FS reported diverse biopsychosocial etiological factors and symptom triggers. Ongoing psychological symptoms and lifetime adverse experiences were associated with worse HRQoL. Future studies will examine these factors in larger samples of individuals with FMS or FS to better understand their shared and distinct etiological underpinnings.
OBJECTIVE: Limited research has directly investigated whether and how placebo effects can be harnessed for the treatment of functional neurological disorder (FND), despite a long-standing and controversial history of int...OBJECTIVE: Limited research has directly investigated whether and how placebo effects can be harnessed for the treatment of functional neurological disorder (FND), despite a long-standing and controversial history of interest in this area. METHODS: A small exploratory study was conducted with adults with a cognitive subtype of FND recruited from a single cognitive neurology center in the United States. Participants were given the expectation of receiving cranial stimulation that could benefit their memory symptoms; however, the intervention was sham transcranial magnetic stimulation (placebo). Outcomes included measures of short-term memory testing, subjective memory rating, and state anxiety before and after stimulation. After the study, the true objective and rationale for investigating placebo effects were explained in a scripted debriefing session. Acceptability of the study design and qualitative feedback were collected. Institutional ethics approval and signed consent were obtained. RESULTS: Three patients (female, N=2; male, N=1; average age=57 years) were recruited. Outcome data were analyzed descriptively at the patient level. Trends of improvement in subjective memory rating, but not objective cognitive test scores, and decreases in state anxiety were observed. After the debriefing session, all patients found the study design to be acceptable (ratings of 70%, 90%, and 100%), and two of the three patients believed that withholding mechanistic information about the intervention was needed to leverage placebo effects as treatment. CONCLUSIONS: In the first study to prospectively investigate the feasibility of harnessing placebo effects for the treatment of FND, promising preliminary findings were obtained, and methods and resources for use in larger future studies are offered.
OBJECTIVE: Neuroimaging studies have identified alterations in both brain structure and functional connectivity in patients with functional neurological disorder (FND). For many patients, FND emerges from physical precip...OBJECTIVE: Neuroimaging studies have identified alterations in both brain structure and functional connectivity in patients with functional neurological disorder (FND). For many patients, FND emerges from physical precipitating events. Nevertheless, there are a limited number of case series in the literature that describe the clinical presentation and neuroimaging correlates of FND following cerebrovascular disease. METHODS: The authors collected data from two clinics in the United Kingdom on 14 cases of acute, improving, or delayed functional neurological symptoms following cerebrovascular events. RESULTS: Most patients had functional neurological symptoms that were localized to cerebrovascular lesions, and the lesions mapped onto regions known to be part of functional networks disrupted in FND, including the thalamus, anterior cingulate gyrus, insula, and temporoparietal junction. CONCLUSIONS: The findings demonstrate that structural lesions can lead to FND symptoms, possibly explained through changes in relevant mechanistic functional networks.
OBJECTIVE: The authors sought to explore the role of iron supplementation in the management of neurodevelopmental disorders among children and youths. METHODS: A systematic review in accordance with Preferred Reporting I...OBJECTIVE: The authors sought to explore the role of iron supplementation in the management of neurodevelopmental disorders among children and youths. METHODS: A systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was undertaken. A subset of results was suitable for meta-analysis. The quality of the evidence and strength of the clinical recommendations were assessed by using the Grading of Recommendations, Assessment, Development, and Evaluation method, and critical appraisal was conducted with the Joanna Briggs Institute critical appraisal tools. RESULTS: Nine articles met inclusion criteria. These articles included studies of attention-deficit hyperactivity disorder (ADHD) (N=7), autism spectrum disorder (N=1), and Tourette's syndrome (N=1). Three randomized controlled trials evaluating iron supplementation for ADHD hyperactivity symptom severity (124 participants: placebo, N=56; supplement, N=68) met inclusion criteria for a meta-analysis. Effect sizes for the placebo and supplement groups were moderate (Cohen's d=0.76) and large (Cohen's d=1.70), respectively, although these differences were not significant. The impact of iron supplementation on inattentive ADHD symptom severity was examined in two trials (75 participants: placebo, N=31; supplement, N=44). Large, nonsignificant effect sizes were demonstrated for the placebo (Cohen's d=1.66) and supplementation (Cohen's d=3.19) groups. The quality of the evidence and strength of the clinical recommendations were considered very low. CONCLUSIONS: Further research is needed to examine the role of iron supplementation in the management of ADHD and neurodevelopmental disorders more generally. Additionally, iron supplementation comes with risks, including death in the case of overdose.
Neuroscience-based patient education has become an evidence-based strategy for enhancing chronic pain treatment. Advances in understanding the neuroscience of functional neurological disorder (FND) may allow similar appr...Neuroscience-based patient education has become an evidence-based strategy for enhancing chronic pain treatment. Advances in understanding the neuroscience of functional neurological disorder (FND) may allow similar approaches to be developed and disseminated to clinicians, given the public health need for greater provider awareness and expertise around the condition. Accordingly, the authors developed an online video module for clinicians that delivers neuroscience-based psychoeducation for FND and assessed whether the intervention would be associated with changes in clinicians' perception of FND patients and knowledge about the condition. The online intervention consisted of a 20-minute video module, including an 8-minute scripted role-play that modeled neuroscience-informed diagnosis delivery. Pre- and postintervention questionnaires were embedded into the online module and included a self-assessment of FND-related perceptions and knowledge and a multiple-choice assessment of retention of the neuroscience-based content. Wilcoxon signed-rank tests and McNemar's tests were used for statistical analyses. Of the 103 individuals who submitted surveys, 40 participants provided a complete data set from before and after the intervention. Following the intervention, self-assessment items showed respondents had significantly greater comfort with diagnosis delivery and treatment options and decreased negative perception of FND patients. The percentage of correct responses on a multiple-choice assessment regarding the functional neuroanatomy of FND was significantly increased. In summary, the online neuroscience-based educational intervention was effective for increasing clinician knowledge about FND and comfort with diagnosis delivery and treatment options. Implementing web-based formats may be a viable and cost-effective approach to disseminating knowledge and basic clinical skills in the care of patients with FND.