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Screening for PTSD and TBI in Veterans using Routine Clinical Laboratory Blood Tests

Xu, Mu; Lin, Ziqiang; Siegel, Carole E; Laska, Eugene M; Abu-Amara, Duna; Genfi, Afia; Newman, Jennifer; Jeffers, Michelle K; Blessing, Esther M; Flanagan, Steven R; Fossati, Silvia; Etkin, Amit; Marmar, Charles R
Post-traumatic stress disorder (PTSD) is a mental disorder diagnosed by clinical interviews, self-report measures and neuropsychological testing. Traumatic brain injury (TBI) can have neuropsychiatric symptoms similar to PTSD. Diagnosing PTSD and TBI is challenging and more so for providers lacking specialized training facing time pressures in primary care and other general medical settings. Diagnosis relies heavily on patient self-report and patients frequently under-report or over-report their symptoms due to stigma or seeking compensation. We aimed to create objective diagnostic screening tests utilizing Clinical Laboratory Improvement Amendments (CLIA) blood tests available in most clinical settings. CLIA blood test results were ascertained in 475 male veterans with and without PTSD and TBI following warzone exposure in Iraq or Afghanistan. Using random forest (RF) methods, four classification models were derived to predict PTSD and TBI status. CLIA features were selected utilizing a stepwise forward variable selection RF procedure. The AUC, accuracy, sensitivity, and specificity were 0.730, 0.706, 0.659, and 0.715, respectively for differentiating PTSD and healthy controls (HC), 0.704, 0.677, 0.671, and 0.681 for TBI vs. HC, 0.739, 0.742, 0.635, and 0.766 for PTSD comorbid with TBI vs HC, and 0.726, 0.723, 0.636, and 0.747 for PTSD vs. TBI. Comorbid alcohol abuse, major depressive disorder, and BMI are not confounders in these RF models. Markers of glucose metabolism and inflammation are among the most significant CLIA features in our models. Routine CLIA blood tests have the potential for discriminating PTSD and TBI cases from healthy controls and from each other. These findings hold promise for the development of accessible and low-cost biomarker tests as screening measures for PTSD and TBI in primary care and specialty settings.
PMCID:9944218
PMID: 36810280
ISSN: 2158-3188
CID: 5448152

PM&R BOLD: The American Academy of Physical Medicine and Rehabilitation's strategic initiative to envision - and effectuate - The future of care across the rehabilitation care continuum

Moon, Cindy H; Groman, Rachel; Jasak, Robert S; Burnetta, Edward C; Gonzalez-Fernandez, Marlis; Annaswamy, Thiru; Jayabalan, Prakash; Venesy, Deborah A; Sereiko, Tracy J; Flanagan, Steven R
PMID: 36349903
ISSN: 1934-1563
CID: 5357312

Early Neurorehabilitation and Recovery from Disorders of Consciousness After Severe COVID-19

Gurin, Lindsey; Evangelist, Megan; Laverty, Patricia; Hanley, Kaitlin; Corcoran, John; Herbsman, Jodi; Im, Brian; Frontera, Jennifer; Flanagan, Steven; Galetta, Steven; Lewis, Ariane
BACKGROUND:Early neurorehabilitation improves outcomes in patients with disorders of consciousness (DoC) after brain injury, but its applicability in COVID-19 is unknown. We describe our experience implementing an early neurorehabilitation protocol for patients with COVID-19-associated DoC in the intensive care unit (ICU) and evaluate factors associated with recovery. METHODS:During the initial COVID-19 surge in New York City between March 10 and May 20, 2020, faced with a disproportionately high number of ICU patients with prolonged unresponsiveness, we developed and implemented an early neurorehabilitation protocol, applying standard practices from brain injury rehabilitation care to the ICU setting. Twenty-one patients with delayed recovery of consciousness after severe COVID-19 participated in a pilot early neurorehabilitation program that included serial Coma Recovery Scale-Revised (CRS-R) assessments, multimodal treatment, and access to clinicians specializing in brain injury medicine. We retrospectively compared clinical features of patients who did and did not recover to the minimally conscious state (MCS) or better, defined as a CRS-R total score (TS) ≥ 8, before discharge. We additionally examined factors associated with best CRS-R TS, last CRS-R TS, hospital length of stay, and time on mechanical ventilation. RESULTS:Patients underwent CRS-R assessments a median of six (interquartile range [IQR] 3-10) times before discharge, beginning a median of 48 days (IQR 40-55) from admission. Twelve (57%) patients recovered to MCS after a median of 8 days (IQR 2-14) off continuous sedation; they had lower body mass index (p = 0.009), lower peak serum C-reactive protein levels (p = 0.023), higher minimum arterial partial pressure of oxygen (p = 0.028), and earlier fentanyl discontinuation (p = 0.018). CRS-R scores fluctuated over time, and the best CRS-R TS was significantly higher than the last CRS-R TS (median 8 [IQR 5-23] vs. 5 [IQR 3-18], p = 0.002). Earlier fentanyl (p = 0.001) and neuromuscular blockade (p = 0.015) discontinuation correlated with a higher last CRS-R TS. CONCLUSIONS:More than half of our cohort of patients with prolonged unresponsiveness following severe COVID-19 recovered to MCS or better before hospital discharge, achieving a clinical benchmark known to have relatively favorable long-term prognostic implications in DoC of other etiologies. Hypoxia, systemic inflammation, sedation, and neuromuscular blockade may impact diagnostic assessment and prognosis, and fluctuations in level of consciousness make serial assessments essential. Early neurorehabilitation of these patients in the ICU can be accomplished but is associated with unique challenges. Further research should evaluate factors associated with longer-term neurologic recovery and benefits of early rehabilitation in patients with severe COVID-19.
PMCID:8491764
PMID: 34611810
ISSN: 1556-0961
CID: 5067712

The effects of plasticity-based cognitive rehabilitation on resting-state functional connectivity in chronic traumatic brain injury: A pilot study

Lindsey, Hannah M; Lazar, Mariana; Mercuri, Giulia; Rath, Joseph F; Bushnik, Tamara; Flanagan, Steven; Voelbel, Gerald T
BACKGROUND:Traumatic brain injury (TBI) often results in chronic impairments to cognitive function, and these may be related to disrupted functional connectivity (FC) of the brain at rest. OBJECTIVE:To investigate changes in default mode network (DMN) FC in adults with chronic TBI following 40 hours of auditory processing speed training. METHODS:Eleven adults with chronic TBI underwent 40-hours of auditory processing speed training over 13-weeks and seven adults with chronic TBI were assigned to a non-intervention control group. For all participants, resting-state FC and cognitive and self-reported function were measured at baseline and at a follow-up visit 13-weeks later. RESULTS:No significant group differences in cognitive function or resting-state FC were observed at baseline. Following training, the intervention group demonstrated objective and subjective improvements on cognitive measures with moderate-to-large effect sizes. Repeated measures ANCOVAs revealed significant (p <  0.001) group×time interactions, suggesting training-related changes in DMN FC, and semipartial correlations demonstrated that these were associated with changes in cognitive functioning. CONCLUSIONS:Changes in the FC between the DMN and other resting-state networks involved in the maintenance and manipulation of internal information, attention, and sensorimotor functioning may be facilitated through consistent participation in plasticity-based auditory processing speed training in adults with chronic TBI.
PMID: 35404295
ISSN: 1878-6448
CID: 5205092

Early Neurorehabilitation and Recovery from Disorders of Consciousness after Severe COVID-19: Findings from a Pilot Feasibility Study [Meeting Abstract]

Gurin, Lindsey; Evangelist, Megan; Laverty, Patricia; Hanley, Kaitlin; Corcoran, John; Herbsman, Jodi; Im, Brian; Frontera, Jennifer; Flanagan, Steven; Galetta, Steven; Lewis, Ariane
ISI:000761085700202
ISSN: 0269-9052
CID: 5243022

Management of Concussion and Persistent Post-Concussive Symptoms for Neurologists

Leddy, John J; Haider, Mohammad Nadir; Noble, James M; Rieger, Brian; Flanagan, Steven; McPherson, Jacob I; Shubin-Stein, Kenneth; Saleem, Ghazala T; Corsaro, Louis; Willer, Barry
PURPOSE OF REVIEW/OBJECTIVE:Concussion is a complex injury that may present as a variety of clinical profiles, which can overlap and reinforce one another. This review summarizes the medical management of patients with concussion and persistent post-concussive symptoms (PPCS). RECENT FINDINGS/RESULTS:Management of concussion and PPCS relies on identifying underlying symptom generators. Treatment options include sub-symptom threshold aerobic exercise, cervical physical therapy, vestibular therapy, vision therapy, cognitive rehabilitation, cognitive behavioral therapy, pharmacological management, or a combination of treatments. Evidence-based treatments have emerged to treat post-concussion symptom generators for sport-related concussion and for patients with PPCS.
PMID: 34817719
ISSN: 1534-6293
CID: 5063672

Clinical Assessment of Concussion and Persistent Post-Concussive Symptoms for Neurologists

Leddy, John J; Haider, Mohammad Nadir; Noble, James M; Rieger, Brian; Flanagan, Steven; McPherson, Jacob I; Shubin-Stein, Kenneth; Saleem, Ghazala T; Corsaro, Louis; Willer, Barry
PURPOSE OF REVIEW/OBJECTIVE:Concussion produces a variety of signs and symptoms. Most patients recover within 2-4 weeks, but a significant minority experiences persistent post-concussive symptoms (PPCS), some of which may be from associated cervical or persistent neurologic sub-system (e.g., vestibular) dysfunction. This review provides evidence-based information for a pertinent history and physical examination of patients with concussion. RECENT FINDINGS/RESULTS:The differential diagnosis of PPCS is based on the mechanism of injury, a thorough medical history and concussion-pertinent neurological and cervical physical examinations. The concussion physical examination focuses on elements of autonomic function, oculomotor and vestibular function, and the cervical spine. Abnormalities identified on physical examination can inform specific forms of rehabilitation to help speed recovery. Emerging data show that there are specific symptom generators after concussion that can be identified by a thorough history, a pertinent physical examination, and adjunct tests when indicated.
PMID: 34817724
ISSN: 1534-6293
CID: 5063692

COVID-19 and Visual Disability: Can't Look and Now Don't Touch

Rizzo, John-Ross; Beheshti, Mahya; Fang, Yi; Flanagan, Steven; Giudice, Nicholas A
PMID: 33354903
ISSN: 1934-1563
CID: 4747472

Traumatic brain injury in older adults

Chapter by: Levine, Jaime; Flanagan, Steven R.; Dams-O"™Connor, Kristen
in: Brain Injury Medicine, Third Edition: Principles and Practice by
[S.l.] : Springer Publishing Company, 2021
pp. 400-413
ISBN: 9780826143051
CID: 5369052

Emotional and autonomic processing of olfactory stimuli is compromised in patients with a history of mild traumatic brain injury

Hilz, Max J; Wang, Ruihao; Liu, Mao; Muresanu, Dafin; Flanagan, Steven; Winder, Klemens; Hösl, Katharina M; Hummel, Thomas
Patients with a history of mild traumatic brain injury (post-mTBI-patients) may have enduring cardiovascular-autonomic dysregulation and emotional problems. Olfactory stimulation (OS) triggers emotional and cardiovascular-autonomic responses which might be compromised in post-mTBI-patients. We therefore evaluated these responses to OS in post-mTBI-patients. In 17 post-mTBI-patients (interval since mTBI 32.4±6.8 months) and 17 age- and sex-matched controls, we recorded respiration, electrocardiographic RR-intervals, systolic, diastolic blood pressures (BPsys, BPdia) before and during pleasant vanilla-stimulation and unpleasant hydrogen-sulphide-(H2S)-stimulation. Participants rated OS related pleasantness, arousal, intensity, and familiarity on 9-point Likert-scales. ANOVAs with post-hoc analyses compared parameters within each group before and during OS. To assess associations between pleasantness, arousal, intensity, and familiarity, we correlated OS-scores within groups (significance: p<0.05). Baseline parameters were similar between groups. Only in controls, vanilla-stimulation significantly lowered BPsys and BPdia, while H2S-stimulation lowered RR-intervals. Vanilla related pleasantness-scores were lower, intensity-scores were higher in patients than controls. During vanilla-stimulation, pleasantness-scores correlated negatively with arousal-scores in controls, while familiarity-scores correlated positively with intensity-scores in patients. During H2S-stimulation, familiarity-scores correlated negatively with pleasantness-scores in controls, while pleasantness-scores correlated negatively with arousal-scores in mTBI patients. Post-mTBI-patients could not change blood pressure or RR-intervals during OS but perceived vanilla stimuli as less pleasant and more intense than did controls. Associations between pleasantness, arousal, intensity, and familiarity differed between groups suggesting different activation of the olfactory network and the central autonomic network upon OS. Subtle lesions within these networks might cause persistent changes in emotional and cognitive odor perception and cardiovascular responses.
PMID: 31298614
ISSN: 1557-9042
CID: 3976882