Factors Associated With Response to Pilot Home-Based Light Therapy for Fatigue Following Traumatic Brain Injury and Stroke

 Fatigue is a massive problem post stroke, so get this written up as a protocol and delivered to all 10 million yearly stroke survivors  now and into the future. You might have to create a great stroke association  to get that delivery done.

At least half of all stroke survivors experience fatigue 

Or is it 70%?

Or is it 40%?

Factors Associated With Response to Pilot Home-Based Light Therapy for Fatigue Following Traumatic Brain Injury and Stroke

Laura J. Connolly^1,2, Shantha M. W. Rajaratnam^2,3,4, Gershon Spitz^1,2, Steven W. Lockley^2,3,4 and Jennie L. Ponsford^1,2*

• ¹Monash Epworth Rehabilitation Research Centre, Epworth Healthcare, Melbourne, VIC, Australia
• ²School of Psychological Sciences, Turner Institute for Brain and Mental Health, Monash University, Melbourne, VIC, Australia
• ³Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, MA, United States
• ⁴Division of Sleep Medicine, Harvard Medical School, Boston, MA, United States

Background: Fatigue and sleep disturbance are common and debilitating problems after brain injury. Light therapy shows promise as a potential treatment. We conducted a trial of in-home light therapy to alleviate fatigue and sleep disturbance. The aim of the current study was to identify factors moderating treatment response.

Methods: Participants were 24 individuals with traumatic brain injury (TBI) (n = 19) or stroke (n = 5) reporting clinically significant fatigue. Outcomes included fatigue on Brief Fatigue Inventory (primary outcome), sleep disturbance on Pittsburgh Sleep Quality Index, reaction time (RT) on Psychomotor Vigilance Task and time spent in productive activity. Interactions of demographic and clinical variables with these outcomes were examined in linear mixed-model analyses.

Results: Whilst there were no variables found to be significantly associated with change in our primary outcome of fatigue, some variables revealed medium or large effect sizes, including chronotype, eye color, injury severity as measured by PTA, and baseline depressive symptoms. Chronotype significantly moderated sleep quality, with evening chronotype being associated with greater improvement during treatment. Injury type significantly predicted mean RT, with stroke participants exhibiting greater post-treatment reduction than TBI. Age significantly predicted productive activity during Treatment, with younger participants showing stronger Treatment effect.

Conclusion: Light therapy may have a greater impact on sleep in younger individuals and those with an evening chronotype. Older individuals may need higher treatment dose to achieve benefit.

Clinical Trial Registration: www.anzctr.org.au, identifier: ACTRN12617000866303.

Introduction

Fatigue and sleep disturbance are debilitating sequelae of traumatic brain injury (TBI) and stroke across the spectrum of severity. These symptoms are reported in 30–70% of cases and impact significantly on daily activities and quality of life (1–4). Frequent sleep disturbances include excessive daytime sleepiness, hypersomnia, insomnia, reduced sleep efficiency, changes to sleep timing and sleep apnea (5, 6). Causes are thought to be multi-factorial, including both injury-related factors and secondary factors such as depression and pain (7, 8).

Pharmacological interventions have not provided long-term solutions to these problems (9–11). Recent studies have, however, offered evidence that light therapy may be an effective avenue for treatment (12–16). In a recent pilot randomized controlled trial involving 24 individuals with TBI or stroke and significant fatigue, we showed that in-home light therapy, consisting of daytime blue-enriched white light (CCT >5,000 K) and blue-depleted light (≤ 3,000 K) 3 h prior to sleep, showed positive trends in impacting fatigue, significantly reduced sleep disturbance and insomnia symptoms, and improved psychomotor vigilance and productive daily activity, relative to a control lighting condition (17). Considerable inter-individual variability was observed in responses to the intervention. There is therefore a need to identify which factors moderated response to the intervention, so that treatment may be targeted toward individuals most likely to benefit.

Only a few studies have examined factors associated with response to light therapy, for the treatment of delayed sleep-wake phase disorder (DSWPD) (18) and seasonal affective disorder (SAD) (19–21). These studies found that mood and sleep-related factors predicted the efficacy of light therapy, with one study finding that clinical effectiveness of bright light treatment (2 h of 2,500–10,000 lux light daily for 7–14 days) (based on the Hamilton Depression Rating Scale) was associated with a greater relative dominance of atypical symptoms of depression prior to treatment, which included symptoms such as hypersomnia, afternoon or evening slump, worse mood in evenings, and carbohydrate craving (19). Age has also been identified as a predictor, with younger age associated with greater treatment response to morning bright light therapy (2,500 lux, 2 h in mornings for 2 weeks) for SAD (21). Conversely, diagnosis of a personality disorder (20) and moderate consumption of alcohol (22) render an individual with SAD less likely to respond positively. Sex differences in response to light therapy have also been observed, with men demonstrating a stronger response to blue-enriched white light (6,500 K, 40 lux, 2 h) in the late evening, indicated by superior sustained attention performance and increased frontal NREM sleep slow-wave activity (23). There has been limited examination of factors associated with light therapy efficacy after brain injury (13–16, 24). In a small pilot study, we previously showed that reductions in fatigue and daytime sleepiness due to morning blue lightbox therapy were not associated with demographic, injury or cognitive characteristics of participants with TBI (12). This present study sought to extend these previous findings by investigating factors that moderate response to in-home light therapy in a larger cohort of TBI and stroke patients.

A number of potential predictive factors were selected a priori on the basis of their known influence on fatigue, sleep and sensitivity to light. Firstly, injury-related factors, such as time post-injury, injury severity, and injury type may moderate treatment response. Recovery is typically greatest in early stages (25), and functional recovery greater in individuals with less severe injury (26), so it is plausible that those with less time post-injury and less severe injury (measured by shorter post-traumatic amnesia duration; PTA), may show greater response to light therapy. Although the causes of fatigue and sleep disturbance after both TBI and stroke are not well-established, and likely multi-factorial, it is conceivable that there may be differences in response to intervention according to injury cause. Biological factors may also be associated with treatment response, including eye color, use of antidepressant medication and chronotype. There is evidence that lighter iris color (27) and antidepressant medication increase the sensitivity of the circadian system to light (28). Greater evening chronotype individuals have also been found to be more responsive to light therapy in groups with depression and bipolar disorder (29, 30). Lastly, an individual's work status (unemployed, working part time or full-time) is likely to correlate to the amount of time spent in the home, and thus the magnitude of exposure to the light therapy, which may in turn moderate treatment response (31).

The aim of the current study was to investigate which factors moderated response to in-home light therapy for individuals with fatigue following TBI and stroke. Predictive factors included level of baseline fatigue, daytime sleepiness and depressive symptoms, age, sex, injury severity measured by post-traumatic amnesia (PTA), time post-injury, injury type (TBI vs. stroke), chronotype, eye color, work status (not working, part time or full time), and use of antidepressant medication. Outcomes included measures of fatigue, sleep disturbance, psychomotor vigilance and productive activity, which were the main outcomes measured in the intervention. A priori, it was hypothesized that younger age, male sex, shorter PTA, less time since injury, injury type (TBI vs. stroke), greater evening chronotype score, unemployed work status, and current use of antidepressant medication would be associated with greater treatment response.