Perioperative insomnia trajectories and functional outcomes after total knee arthroplasty.

ABSTRACT: Longitudinal total knee arthroplasty (TKA) studies indicate that a substantial percentage of patients continue to experience clinically significant pain and functional impairment after surgery. Insomnia has been associated with poorer surgical outcomes; however, previous work has largely focused on long-term postsurgical insomnia. This study builds on previous work by examining sleep and pain outcomes about perioperative insomnia trajectories. Insomnia symptoms (using the Insomnia Severity Index) during the acute perioperative period (2 weeks pre-TKA to 6 weeks post-TKA) were used to classify participants into perioperative insomnia trajectories: (1) No Insomnia (ISI < 8), (2) New Insomnia (baseline < 8; postoperative ≥ 8 or ≥6-point increase), (3) Improved Insomnia (baseline ≥ 8, postoperative < 8 or ≥6-point decrease), and (4) Persistent Insomnia (ISI ≥ 8). Insomnia, pain, and physical functioning were assessed in participants with knee osteoarthritis (n = 173; M age = 65 ± 8.3, 57.8% female) at 5 time points: 2 weeks pre-TKA, post-TKA: 6 weeks, 3 months, 6 months, and 12 months. Significant main effects were seen for insomnia trajectory and time, and trajectory-by-time interactions for postoperative insomnia, pain severity, and physical functioning ( P' s < 0.05). The Persistent Insomnia trajectory had the worst postoperative pain at all follow-ups and marked insomnia and physical functioning impairment post-TKA ( P' s < 0.05). The New Insomnia trajectory had notable long-term insomnia (6 weeks to 6 months) and acute (6 weeks) postoperative pain and physical functioning ( P' s < 0.05). Findings indicated a significant relationship between perioperative insomnia trajectory and postoperative outcomes. Results of this study suggest that targeting presurgical insomnia and preventing the development of acute postoperative insomnia may improve long-term postoperative outcomes, with an emphasis on persistent perioperative insomnia due to poorer associated outcomes.

Dialectical behavior therapy skills training for individuals with multiple sclerosis and their support partners: A pilot randomized controlled trial.

BACKGROUND: Symptoms of anxiety, depression, and emotion dysregulation are common among individuals with MS and their support partners. Dialectical behavior therapy (DBT) - a type of cognitive behavioral intervention - may be a promising treatment for individuals affected by MS. This pilot randomized controlled trial (RCT) assessed the effects and feasibility of remotely delivered DBT skills on anxiety and depression symptoms and emotion dysregulation in individuals with MS and their support partners. METHODS: This study featured a single-masked, two-arm, parallel group design. Twenty pairs of individuals with MS and their support partners (n = 40) were randomized to 12 weeks of DBT or facilitated peer support (FPS). Masked assessments were completed at weeks 0 (baseline), 13 (post-intervention), and 26 (follow-up). RESULTS: At post-intervention (primary endpoint), participants randomized to DBT exhibited significantly greater reductions in anxiety and depression symptoms compared to FPS (B = 4.45, p = .04, Cohen's d = 0.57). Secondary outcomes of emotion dysregulation and well-being favored the DBT group but did not reach statistical significance (ds = 0.51, ps = 0.07). Effects were not maintained at follow-up. Most (86%) individuals screened were eligible for the trial, and retention (70%) did not differ between study arms. CONCLUSIONS: This pilot RCT provides encouraging evidence that DBT skills is feasible and may improve depression, anxiety, and emotion dysregulation for individuals with MS and their support partners. Future research is needed to optimize maintenance of DBT skills, investigate mechanisms for these improvements, and replicate these promising effects in a fully powered trial.

Depressive symptoms and fatigue as predictors of objective-subjective discrepancies in cognitive function in multiple sclerosis.

OBJECTIVE: To examine the degree to which depressive symptoms and fatigue in individuals with multiple sclerosis (MS) are associated with discrepancies between subjective and objective cognitive impairment. METHODS: Ninety-nine adults with MS who were receiving care in a university-affiliated MS center completed the Patient Health Questionnaire-8 (PHQ-8), Fatigue Severity Scale (FSS), MS Neuropsychological Screening Questionnaire (MSNQ), and Brief International Cognitive Assessment for MS (BICAMS). Participants were classified as "Accurates," "Underestimators," or "Overestimators" based on discrepancies between their MSNQ (subjective) and BICAMS (objective) scores. Underestimators were individuals whose subjective scores were significantly worse than their objective scores. Overestimators exhibited the opposite profile. RESULTS: The PHQ-8 (r = 0.58) and FSS (r = 0.48) significantly correlated with the MSNQ, but not with the BICAMS (rs < 0.07). Underestimators (i.e., participants who underestimated their objective cognitive functioning) exhibited higher PHQ-8 and FSS scores compared to Accurates (ps < 0.01) and Overestimators (ps < 0.01). Optimal cut-scores of ≥6 on the PHQ-8 and ≥36 on the FSS provided fair accuracy (78% and 74%) for identifying Underestimators. Identification of Underestimators based on PHQ-8 and FSS scores was not moderated by any demographic or MS clinical variables. CONCLUSIONS: In the presence of mild levels of depression or significant fatigue, subjective cognitive measures are unlikely to provide accurate estimates of objective cognitive functioning. Objective cognitive measures are required for accurate identification of cognitive impairment.

Diagnostic and Clinical Utility of the GAD-2 for Screening Anxiety Symptoms in Individuals With Multiple Sclerosis.

OBJECTIVE: To assess the diagnostic and clinical utility of the 2-item Generalized Anxiety Disorder Scale (GAD-2) for screening anxiety symptoms in individuals with multiple sclerosis (MS). DESIGN: Cross-sectional. SETTING: University-affiliated MS neurology and rehabilitation center. PARTICIPANTS: The sample comprised adults (N=99) (ages 19-72; mean ± SD=46.2±13.0; 75% women) with a physician-confirmed MS diagnosis who were receiving care in a university-affiliated MS center. Disease durations ranged from 1 to 37 years (mean ± SD=10.7±8.4). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Participants completed the 7-item Generalized Anxiety Disorder Scale (GAD-7) and GAD-2. Internal consistency was calculated for both measures. Area under the receiver operating characteristics curve (AUC), the 95% confidence interval for the AUC, and Youden's J were calculated to determine the optimal GAD-2 cutoff score for identifying clinically significant anxiety symptoms, as defined by the previously validated GAD-7 cutoff score of ≥8. RESULTS: Internal consistency was excellent for the GAD-7 (Cronbach α=.91) and acceptable for the GAD-2 (α=.77), and the measures were highly correlated (r=.94). The GAD-2 had excellent overall accuracy for identifying clinically significant anxiety symptoms (AUC=0.97; 95% confidence interval, 0.94-1.00). A GAD-2 cutoff score of ≥3 provided an optimal balance of good sensitivity (0.87) and excellent specificity (0.92) for detecting clinically significant anxiety symptoms. Alternatively, a cutoff score of ≥2 provided excellent sensitivity (1.00) and fair specificity (0.76). CONCLUSIONS: The GAD-2 is a clinically useful and psychometrically valid tool for screening anxiety symptoms in MS rehabilitation and neurology care settings. Importantly, this tool has the potential to identify individuals with MS who are at risk for anxiety disorders and who may benefit from rehabilitation psychology interventions to ultimately improve functioning and quality of life.

In vivo evidence of oxidative stress in brains of patients with progressive multiple sclerosis.

BACKGROUND: The oxidative stress hypothesis links neurodegeneration in the later, progressive stages of multiple sclerosis (MS) to the loss of a major brain antioxidant, glutathione (GSH). OBJECTIVE: We measured GSH concentrations among major MS subtypes and examined the relationships with other indices of disease status including physical disability and magnetic resonance imaging (MRI) measures. METHODS: GSH mapping was performed on the fronto-parietal region of patients with relapsing-remitting multiple sclerosis (RRMS, n = 21), primary progressive multiple sclerosis (PPMS, n = 20), secondary progressive multiple sclerosis (SPMS, n = 20), and controls ( n = 28) using GSH chemical shift imaging. Between-group comparisons were performed on all variables (GSH, T2-lesion, atrophy, Expanded Disability Status Scale (EDSS)). RESULTS: Patients with MS had substantially lower GSH concentrations than controls, and GSH was lower in progressive MS (PPMS and SPMS) compared with RRMS. GSH concentrations were not significantly different between PPMS and SPMS, or between RRMS and controls. Brain atrophy was significant in both RRMS and progressive MS compared with controls. CONCLUSION: Markedly lower GSH in progressive MS than RRMS indicates more prominent involvement of oxidative stress in the progressive stage of MS than the inflammatory stage. The association between GSH and brain atrophy suggests the important role of oxidative stress contributing to neurodegeneration in progressive MS, as suggested in other neurodegenerative diseases.

Longitudinal changes of cerebral glutathione (GSH) levels associated with the clinical course of disease progression in patients with secondary progressive multiple sclerosis.

BACKGROUND: Increased oxidative stress leads to loss of glutathione (GSH). We have reported lower cerebral GSH in patients with secondary progressive multiple sclerosis (SPMS), indicating the involvement of oxidative stress in multiple sclerosis (MS) pathophysiology. OBJECTIVE: This study expanded upon our earlier work by examining longitudinal changes in cerebral GSH in patients with SPMS in relation to their clinical status. METHODS: A total of 13 patients with SPMS (Expanded Disability Status Scale (EDSS) = 4.0-6.5; MS duration = 21.2 ± 8.7 years) and 12 controls were studied over 3-5 years. GSH mapping was acquired from frontal and parietal regions using a multiple quantum chemical shift imaging technique at 3 T. Clinical assessments of the patient's disability included EDSS, gait, motor strength, ataxia, tremor, brainstem function and vision changes. RESULTS: Brain GSH concentrations in patients were lower than those in controls for both baseline and 3- to 5-year follow-ups. Longitudinal GSH changes of patients were associated with their neurologist's blinded appraisal of their clinical progression. Patients judged to have worsening clinical status had significantly greater declines in frontal GSH concentrations than those with stable clinical status. CONCLUSION: GSH provides a distinct measure associated with the disease progression in SPMS, possibly due to its dynamic alignment with pathogenic processes of MS related to oxidative stress.