Jason W. Krellman

Incidence and risk factors of posttraumatic seizures following traumatic brain injury: A Traumatic Brain Injury Model Systems Study

Determine incidence of posttraumatic seizure (PTS) following traumatic brain injury (TBI) among individuals with moderate‐to‐severe TBI requiring rehabilitation and surviving at least 5 years.

The relationship between self-reported sleep disturbance and polysomnography in individuals with traumatic brain injury

Abstract Primary objective: To characterize sleep architecture and self-reported sleep quality, fatigue and daytime sleepiness in individuals with TBI. Possible relationships between sleep architecture and self-reported sleep quality, fatigue and daytime sleepiness were examined. Methods: Forty-four community-dwelling adults with TBI completed the Pittsburgh Sleep Quality Index (PSQI), Multidimensional Assessment of Fatigue (MAF) and Epworth Sleepiness Scale (ESS). They underwent two nights of in-laboratory nocturnal polysomnography (NPSG). Pearson product-moment correlation coefficients and hierarchical linear regression was used to analyse the data. Results: Based on the PSQI cut-off score of ≥ 10, 22 participants were characterized as poor sleepers. Twenty-seven participants met criteria for clinically significant fatigue as measured by the GFI of the MAF. Fourteen participants met criteria for excessive daytime sleepiness as measured by the ESS. Poor sleep quality was associated with poor sleep efficiency, short duration of stage 2 sleep and long duration of rapid eye movement sleep. There was little-to-no association between high levels of fatigue or daytime sleepiness with NPSG sleep parameters. Conclusions: A high proportion of the sample endorsed poor sleep quality, fatigue and daytime sleepiness. Those who reported poorer sleep quality evidenced a shorter proportion of time spent in stage 2 sleep. These findings suggest that disruptions in stage 2 sleep might underlie the symptoms of sleep disturbance experienced following TBI.

Predictors of Follow-Up Completeness in Longitudinal Research on Traumatic Brain Injury: Findings From the National Institute on Disability and Rehabilitation Research Traumatic Brain Injury Model Systems Program

OBJECTIVE To identify baseline participant variables in the domains of demographics, medical/psychosocial history, injury characteristics, and postinjury functional status associated with longitudinal follow-up completeness in persons with traumatic brain injury (TBI) using the TBI Model Systems (TBIMS) National Database (NDB). DESIGN Exhaustive chi-square automatic interaction detection was used to identify factors that classified participants according to level of follow-up completeness. SETTING Retrospective analysis of a multi-center longitudinal database. PARTICIPANTS Individuals (N=8249) enrolled in the TBIMS NDB between 1989 and 2009 who were eligible for at least the first (year 1) follow-up up to the fifth (year 15) follow-up. INTERVENTIONS None. MAIN OUTCOME MEASURES Follow-up completeness as defined by 6 different longitudinal response patterns (LRPs): completing all follow-ups, wave nonresponse, dropping out, completing no follow-ups without formally withdrawing, formally withdrawing before completing any follow-ups, and formally withdrawing after completing some follow-ups. RESULTS Completing all follow-ups was associated with higher levels of education, living with parents or others, and having acute care payer data entered in the NDB. Subgroups more vulnerable to loss to follow-up (LTFU) included those with less education, racial/ethnic minority backgrounds, those with better motor functioning on rehabilitation discharge, and those for whom baseline data on education, employment, and acute care payer were not collected. No subgroups were found to be more likely to have the LRPs of dropping out or formal withdrawal. CONCLUSIONS These data identify subgroups in which retention strategies beyond those most commonly used might reduce LTFU in longitudinal studies of persons with TBI, such as the TBIMS, and suggest future investigations into factors associated with missing baseline data.

Prognostic models for predicting posttraumatic seizures during acute hospitalization, and at 1 and 2 years following traumatic brain injury.

Posttraumatic seizures (PTS) are well‐recognized acute and chronic complications of traumatic brain injury (TBI). Risk factors have been identified, but considerable variability in who develops PTS remains. Existing PTS prognostic models are not widely adopted for clinical use and do not reflect current trends in injury, diagnosis, or care. We aimed to develop and internally validate preliminary prognostic regression models to predict PTS during acute care hospitalization, and at year 1 and year 2 postinjury.

Can Cognitive Behavioral Therapy for Insomnia also treat fatigue, pain, and mood symptoms in individuals with traumatic brain injury? – A multiple case report

BACKGROUND Individuals with traumatic brain injury (TBI) often develop sleep disorders post-injury. The most common one is insomnia, which can exacerbate other post-injury symptoms, including fatigue, impaired cognition, depression, anxiety, and pain. Cognitive Behavioral Therapy for Insomnia (CBT-I) is a manualized treatment that effectively treats insomnia with secondary effects on cognition, mood, and pain in various populations. OBJECTIVE This paper reviews the use of CBT-I for three participants with TBI of different severities. METHODS Pre- and post-treatment assessments of insomnia, fatigue, depression, anxiety, and pain were conducted. Mood was further assessed at follow-up. Minimal clinically important difference (MCID) scores derived from the research literature were used to establish clinically meaningful symptom improvement on self-report questionnaires. RESULTS The reduction in insomnia severity scores for all three participants were not large enough to be considered a clinically significant improvement following CBT-I, although trends toward improvement were observed. However, all participants showed clinically significant reductions in anxiety at post-treatment; the effects persisted for 2 participants at follow-up. Reductions in depression symptoms were observed for 2 participants at post-treatment, and treatment effects persisted for 1 participant at follow-up. One participant endorsed clinically significant improvements in fatigue and pain severity. CONCLUSIONS We conclude that CBT-I may provide secondary benefits for symptoms commonly experienced by individuals with TBI, especially mood disturbances.

Prevalence, Risk Factors, and Correlates of Anxiety at 1 Year After Moderate to Severe Traumatic Brain Injury

OBJECTIVE To determine at 1 year after moderate to severe traumatic brain injury the (1) rate of clinically significant anxiety; (2) rates of specific symptoms of anxiety; (3) risk factors for anxiety; and (4) associations of anxiety with other 1-year outcomes, including participation and quality of life. DESIGN Prospective longitudinal observational study. SETTING Inpatient rehabilitation centers, with data capture at injury and 1-year follow-up. PARTICIPANTS Persons with moderate to severe traumatic brain injury who were enrolled in the Traumatic Brain Injury Model Systems database (N=1838). INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES The 7-item Generalized Anxiety Disorder Scale, Patient Health Questionnaire (9-item screen for depression), FIM, Participation Assessment with Recombined Tools-Objective, and Satisfaction with Life Scale. RESULTS Clinically significant anxiety was reported by 21% of the participants. Of these, >80% reported interference with daily activities, with the most common symptoms being excessive worry and irritability. A common pattern was comorbid anxiety and depression, with smaller proportions reporting either disorder alone. Anxiety had large effect sizes with respect to life satisfaction and cognitive disability and medium to small effect sizes relative to societal participation and self-care. Middle age, black race, lower socioeconomic status, preinjury mental health treatment, and at least 1 traumatic brain injury prior to the index injury were all risk factors for later anxiety. CONCLUSIONS Anxiety should be screened, fully evaluated, and treated after moderate to severe traumatic brain injury. Worry and irritability might be treated with pharmacologic agents or relatively simple behavioral interventions, which should be further researched in this population.

Acute Trauma Factor Associations With Suicidality Across the First 5 Years After Traumatic Brain Injury

OBJECTIVE To determine whether severity of head and extracranial injuries (ECI) is associated with suicidal ideation (SI) or suicide attempt (SA) after traumatic brain injury (TBI). DESIGN Factors associated with SI and SA were assessed in this inception cohort study using data collected 1, 2, and 5 years post-TBI from the National Trauma Data Bank and Traumatic Brain Injury Model Systems (TBIMS) databases. SETTING Level I trauma centers, inpatient rehabilitation centers, and the community. PARTICIPANTS Participants with TBI from 15 TBIMS Centers with linked National Trauma Data Bank trauma data (N=3575). INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES SI was measured via the Patient Health Questionnaire 9 (question 9). SA in the last year was assessed via interview. ECI was measured by the Injury Severity Scale (nonhead) and categorized as none, mild, moderate, or severe. RESULTS There were 293 (8.2%) participants who had SI without SA and 109 (3.0%) who had SA at least once in the first 5 years postinjury. Random effects logit modeling showed a higher likelihood of SI when ECI was severe (odds ratio=2.73; 95% confidence interval, 1.55-4.82; P=.001). Drug use at time of injury was also associated with SI (odds ratio=1.69; 95% confidence interval, 1.11-2.86; P=.015). Severity of ECI was not associated with SA. CONCLUSIONS Severe ECI carried a nearly 3-fold increase in the odds of SI after TBI, but it was not related to SA. Head injury severity and less severe ECI were not associated with SI or SA. These findings warrant additional work to identify factors associated with severe ECI that make individuals more susceptible to SI after TBI.

Post-traumatic epilepsy associations with mental health outcomes in the first two years after moderate to severe TBI: A TBI Model Systems analysis

PURPOSE Research suggests that there are reciprocal relationships between mental health (MH) disorders and epilepsy risk. However, MH relationships to post-traumatic epilepsy (PTE) have not been explored. Thus, the objective of this study was to assess associations between PTE and frequency of depression and/or anxiety in a cohort of individuals with moderate-to-severe TBI who received acute inpatient rehabilitation. METHODS Multivariate regression models were developed using a recent (2010-2012) cohort (n=867 unique participants) from the TBI Model Systems (TBIMS) National Database, a time frame during which self-reported seizures, depression [Patient Health Questionnaire (PHQ)-9], and anxiety [Generalized Anxiety Disorder (GAD-7)] follow-up measures were concurrently collected at year-1 and year-2 after injury. RESULTS PTE did not significantly contribute to depression status in either the year-1 or year-2 cohort, nor did it contribute significantly to anxiety status in the year-1 cohort, after controlling for other known depression and anxiety predictors. However, those with PTE in year-2 had 3.34 times the odds (p=.002) of having clinically significant anxiety, even after accounting for other relevant predictors. In this model, participants who self-identified as Black were also more likely to report clinical symptoms of anxiety than those who identified as White. PTE was the only significant predictor of comorbid depression and anxiety at year-2 (Odds Ratio 2.71; p=0.049). CONCLUSIONS Our data suggest that PTE is associated with MH outcomes 2years after TBI, findings whose significance may reflect reciprocal, biological, psychological, and/or experiential factors contributing to and resulting from both PTE and MH status post-TBI. Future work should consider temporal and reciprocal relationships between PTE and MH as well as if/how treatment of each condition influences biosusceptibility to the other condition.

The Relationship between Sleep Architecture and Symptoms of Sleep Disturbance in Individuals with Traumatic Brain Injury

Objective: To measure sleep architecture in individuals with TBI and determine its relationship with self-reported sleep quality, fatigue, and daytime sleepiness. Design: Participants: completed self-report measures and underwent two nights of in-laboratory nocturnal polysomnography. Setting: General community. Participants: 46 individuals with mild to severe TBI. Inclusion criteria included age between 18 years to 65 years and a documented TBI as a result of a blow to the head with a loss of consciousness or period of being dazed and confused (e.g., EMS report, hospital record, physician record, or a positive screen on the Brain Injury Screening Questionnaire). Participants: were required to be at least one year post injury (SD Z 13.33 years, range 1.17 years e 56.33 years), English-speaking, and have at least a sixth-grade reading level. No use of Modafinil, amphetamines or soporific medications (e.g., zolpidem, zolpidem MR, eszopiclone, zaleplon, sedating antidepressants, melatonin, valerian root, Benedryl, Ramelteon or chloral hydrate) was allowed 72 hours prior to polysomnography. Use of medications known to cause hypersomnolence (e.g. barbiturates, benzodiazepines, opiates) was not allowed for seven days prior to study. Exclusion criteria included active hepatic or renal failure (which may lead to hypersomnia), active substance abuse disorder, prior or current psychotic disorder, pre-existing neurological disorder or a brain injury with an etiology other than trauma, untreated hypothyroidism and any medical condition or reason that, in the investigator’s opinion, might make the participant unsuitable to participate. All participants were recruited through flyer postings in the Mount Sinai Medical Center and through healthcare provider referrals. The study was approved by the institutional review board of Icahn School of Medicine at Mount Sinai. Informed consent was obtained prior to screening to determine whether or not they met inclusion/exclusion criteria. Interventions: Not applicable. Main Outcome Measure(s): The measures included self-report measures of sleep quality (Pittsburgh Sleep Quality Index; PSQI), fatigue (Multidimensional Assessment of Fatigue; MAF), daytime sleepiness (Epworth Sleepiness Scale; ESS), and nocturnal polysomnography (NPSG) from which sleep efficiency, sleep onset latency, REM latency, wake time after sleep onset, and percentage of stage 1, 2, 3, and REM 4 sleep were extracted. Results: Pearson product-moment correlation coefficients were used to analyze the association between responses on self-report questionnaires. Hierarchical linear regression was used to analyze the association between NPSG sleep parameters and self-report questionnaires, adjusting for age, sex, body mass index, sleep apnea, and TBI severity. Poor sleep quality as measured by the PSQI was associated with fatigue as measured by the MAF. Poor sleep quality was associated with poor sleep efficiency, short duration of stage 2 sleep, and long duration of rapid eye movement sleep. There was a weak association between high levels of fatigue and poor sleep efficiency. Daytime sleepiness as assessed was not associated with any NPSG sleep parameters. Conclusions: In this sample of TBI survivors, those who reported poor sleep quality evidenced shorter time spent in stage 2 sleep compared to those who reported better sleep quality. These findings suggest that disruptions in stage 2 sleep might underlie the symptoms of sleep disturbance experienced following TBI.