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

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.

Management of Concussion and Persistent Post-Concussive Symptoms for Neurologists.

PURPOSE OF REVIEW: 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: 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.

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

PURPOSE OF REVIEW: 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: 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.

Valsalva maneuver unveils central baroreflex dysfunction with altered blood pressure control in persons with a history of mild traumatic brain injury.

BACKGROUND: Patients with a history of mild TBI (post-mTBI-patients) have an unexplained increase in long-term mortality which might be related to central autonomic dysregulation (CAD). We investigated whether standardized baroreflex-loading, induced by a Valsalva maneuver (VM), unveils CAD in otherwise healthy post-mTBI-patients. METHODS: In 29 healthy persons (31.3 ± 12.2 years; 9 women) and 25 post-mTBI-patients (35.0 ± 13.2 years, 7 women, 4-98 months post-injury), we monitored respiration (RESP), RR-intervals (RRI) and systolic blood pressure (BP) at rest and during three VMs. At rest, we calculated parameters of total autonomic modulation [RRI-coefficient-of-variation (CV), RRI-standard-deviation (RRI-SD), RRI-total-powers], of sympathetic [RRI-low-frequency-powers (LF), BP-LF-powers] and parasympathetic modulation [square-root-of-mean-squared-differences-of-successive-RRIs (RMSSD), RRI-high-frequency-powers (HF)], the index of sympatho-vagal balance (RRI LF/HF-ratios), and baroreflex sensitivity (BRS). We calculated Valsalva-ratios (VR) and times from lowest to highest RRIs after strain (VR-time) as indices of parasympathetic activation, intervals from highest systolic BP-values after strain-release to the time when systolic BP had fallen by 90 % of the differences between peak-phase-IV-BP and baseline-BP (90 %-BP-normalization-times), and velocities of BP-normalization (90 %-BP-normalization-velocities) as indices of sympathetic withdrawal. We compared patient- and control-parameters before and during VM (Mann-Whitney-U-tests or t-tests; significance: P < 0.05). RESULTS: At rest, RRI-CVs, RRI-SDs, RRI-total-powers, RRI-LF-powers, BP-LF-powers, RRI-RMSSDs, RRI-HF-powers, and BRS were lower in patients than controls. During VMs, 90 %-BP-normalization-times were longer, and 90 %-BP-normalization-velocities were lower in patients than controls (P < 0.05). CONCLUSIONS: Reduced autonomic modulation at rest and delayed BP-decrease after VM-induced baroreflex-loading indicate subtle CAD with altered baroreflex adjustment to challenge. More severe autonomic challenge might trigger more prominent cardiovascular dysregulation and thus contribute to increased mortality risk in post-mTBI-patients.

Invited Commentary on "Centers for Disease Control and Prevention Report to Congress: Traumatic Brain Injury in the United States: Epidemiology and Rehabilitation".

Traumatic brain injury (TBI) is a significant health problem, afflicting millions of people worldwide. Despite increasing awareness of its burden on patients, families, and society, much remains unknown regarding TBI incidence, how best to assess outcomes post-injury, and the most effective means of providing rehabilitation services. The Centers for Disease Control and Prevention recently published recommendations to Congress that address these critical knowledge gaps. The report is the end product of work completed by a notable panel of experts and stakeholders that makes overarching recommendations aimed at addressing knowledge gaps in TBI, with the ultimate goal of decreasing injury occurrence and improving outcomes. It is a succinct and powerful report that should serve as a call to action to fund innovative research and reverse a trend in health care that restricts access to rehabilitation services.

A Comprehensive and Broad Approach to Resting-State Functional Connectivity in Adult Patients with Mild Traumatic Brain Injury.

BACKGROUND AND PURPOSE: Several recent works using resting-state fMRI suggest possible alterations of resting-state functional connectivity after mild traumatic brain injury. However, the literature is plagued by various analysis approaches and small study cohorts, resulting in an inconsistent array of reported findings. In this study, we aimed to investigate differences in whole-brain resting-state functional connectivity between adult patients with mild traumatic brain injury within 1 month of injury and healthy control subjects using several comprehensive resting-state functional connectivity measurement methods and analyses. MATERIALS AND METHODS: A total of 123 subjects (72 patients with mild traumatic brain injury and 51 healthy controls) were included. A standard fMRI preprocessing pipeline was used. ROI/seed-based analyses were conducted using 4 standard brain parcellation methods, and the independent component analysis method was applied to measure resting-state functional connectivity. The fractional amplitude of low-frequency fluctuations was also measured. Group comparisons were performed on all measurements with appropriate whole-brain multilevel statistical analysis and correction. RESULTS: There were no significant differences in age, sex, education, and hand preference between groups as well as no significant correlation between all measurements and these potential confounders. We found that each resting-state functional connectivity measurement revealed various regions or connections that were different between groups. However, after we corrected for multiple comparisons, the results showed no statistically significant differences between groups in terms of resting-state functional connectivity across methods and analyses. CONCLUSIONS: Although previous studies point to multiple regions and networks as possible mild traumatic brain injury biomarkers, this study shows that the effect of mild injury on brain resting-state functional connectivity has not survived after rigorous statistical correction. A further study using subject-level connectivity analyses may be necessary due to both subtle and variable effects of mild traumatic brain injury on brain functional connectivity across individuals.

Callosal Interhemispheric Communication in Mild Traumatic Brain Injury: A Mediation Analysis on WM Microstructure Effects.

BACKGROUND AND PURPOSE: Because the corpus callosum connects the left and right hemispheres and a variety of WM bundles across the brain in complex ways, damage to the neighboring WM microstructure may specifically disrupt interhemispheric communication through the corpus callosum following mild traumatic brain injury. Here we use a mediation framework to investigate how callosal interhemispheric communication is affected by WM microstructure in mild traumatic brain injury. MATERIALS AND METHODS: Multishell diffusion MR imaging was performed on 23 patients with mild traumatic brain injury within 1 month of injury and 17 healthy controls, deriving 11 diffusion metrics, including DTI, diffusional kurtosis imaging, and compartment-specific standard model parameters. Interhemispheric processing speed was assessed using the interhemispheric speed of processing task (IHSPT) by measuring the latency between word presentation to the 2 hemivisual fields and oral word articulation. Mediation analysis was performed to assess the indirect effect of neighboring WM microstructures on the relationship between the corpus callosum and IHSPT performance. In addition, we conducted a univariate correlation analysis to investigate the direct association between callosal microstructures and IHSPT performance as well as a multivariate regression analysis to jointly evaluate both callosal and neighboring WM microstructures in association with IHSPT scores for each group. RESULTS: Several significant mediators in the relationships between callosal microstructure and IHSPT performance were found in healthy controls. However, patients with mild traumatic brain injury appeared to lose such normal associations when microstructural changes occurred compared with healthy controls. CONCLUSIONS: This study investigates the effects of neighboring WM microstructure on callosal interhemispheric communication in healthy controls and patients with mild traumatic brain injury, highlighting that neighboring noncallosal WM microstructures are involved in callosal interhemispheric communication and information transfer. Further longitudinal studies may provide insight into the temporal dynamics of interhemispheric recovery following mild traumatic brain injury.

TWIST1 associates with NF-κB subunit RELA via carboxyl-terminal WR domain to promote cell autonomous invasion through IL8 production.

BACKGROUND: Metastasis is the primary cause of death for cancer patients. TWIST1, an evolutionarily conserved basic helix-loop-helix (bHLH) transcription factor, is a strong promoter of metastatic spread and its expression is elevated in many advanced human carcinomas. However, the molecular events triggered by TWIST1 to motivate dissemination of cancer cells are largely unknown. RESULTS: Here we show that TWIST1 induces the production of interleukin 8 (IL8), which activates matrix metalloproteinases and promotes invasion of breast epithelial and cancer cells. In this novel mechanism, TWIST1-mediated IL8 transcription is induced through the TWIST1 carboxy-terminal WR (Trp-Arg) domain instead of the classic DNA binding bHLH domain. Co-immunoprecipitation analyses revealed that the WR domain mediates the formation of a protein complex comprised of TWIST1 and the nuclear factor-kappaB (NF-κB) subunit RELA (p65/NF-κB3), which synergistically activates the transcriptional activity of NF-κB. This activation leads to increased DNA binding affinity of RELA to the IL8 promoter and thus induces the expression of the cytokine. Blockage of IL8 signaling by IL8 neutralizing antibodies or receptor inhibition reduced the invasiveness of both breast epithelial and cancer cells, indicating that TWIST1 induces autonomous cell invasion by establishing an IL8 antocrine loop. CONCLUSIONS: Our data demonstrate that the TWIST1 WR domain plays a critical role in TWIST1-induced IL8 expression through interactions with and activation of NF-κB. The produced IL8 signals through an autocrine loop and promotes extracellular matrix degradation to enable cell invasion across the basement membrane.

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

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.

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

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.

Emotional and Autonomic Processing of Olfactory Stimuli Is Compromised in Patients with a History of Mild Traumatic Brain Injury.

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 that 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, and systolic and 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. Analyses of variance (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, whereas 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, whereas familiarity scores correlated positively with intensity scores in patients. During H2S stimulation, familiarity scores correlated negatively with pleasantness scores in controls, whereas pleasantness scores correlated negatively with arousal scores in mTBI patients. Post-mTBI patients could not change BP 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.

MTBI Identification From Diffusion MR Images Using Bag of Adversarial Visual Features.

In this paper, we propose bag of adversarial features (BAFs) for identifying mild traumatic brain injury (MTBI) patients from their diffusion magnetic resonance images (MRIs) (obtained within one month of injury) by incorporating unsupervised feature learning techniques. MTBI is a growing public health problem with an estimated incidence of over 1.7 million people annually in USA. Diagnosis is based on clinical history and symptoms, and accurate, concrete measures of injury are lacking. Unlike most of the previous works, which use hand-crafted features extracted from different parts of brain for MTBI classification, we employ feature learning algorithms to learn more discriminative representation for this task. A major challenge in this field thus far is the relatively small number of subjects available for training. This makes it difficult to use an end-to-end convolutional neural network to directly classify a subject from MRIs. To overcome this challenge, we first apply an adversarial auto-encoder (with convolutional structure) to learn patch-level features, from overlapping image patches extracted from different brain regions. We then aggregate these features through a bag-of-words approach. We perform an extensive experimental study on a dataset of 227 subjects (including 109 MTBI patients, and 118 age and sex-matched healthy controls) and compare the bag-of-deep-features with several previous approaches. Our experimental results show that the BAF significantly outperforms earlier works relying on the mean values of MR metrics in selected brain regions.

MRI findings in the painful poststroke shoulder.

BACKGROUND AND PURPOSE: We describe the structural abnormalities in the painful shoulder of stroke survivors and their relationships to clinical characteristics. Method- Eighty-nine chronic stroke survivors with poststroke shoulder pain underwent T1- and T2-weighted multiplanar, multisequence MRI of the painful paretic shoulder. All scans were reviewed by one radiologist for the following abnormalities: rotator cuff, biceps and deltoid tears, tendinopathies and atrophy, subacromial bursa fluid, labral ligamentous complex abnormalities, and acromioclavicular capsular hypertrophy. Clinical variables included subject demographics, stroke characteristics, and the Brief Pain Inventory Questions 12. The relationship between MRI findings and clinical characteristics was assessed through logistic regression. RESULTS: Thirty-five percent of subjects exhibited a tear of at least one rotator cuff, biceps or deltoid muscle. Fifty-three percent of subjects exhibited tendinopathy of at least one rotator cuff, bicep or deltoid muscle. The prevalence of rotator cuff tears increased with age. However, rotator cuff tears and rotator cuff and deltoid tendinopathies were not related to severity of poststroke shoulder pain. In approximately 20% of cases, rotator cuff and deltoid muscles exhibited evidence of atrophy. Atrophy was associated with reduced motor strength and reduced severity of shoulder pain. CONCLUSIONS: Rotator cuff tears and rotator cuff and deltoid tendinopathies are highly prevalent in poststroke shoulder pain. However, their relationship to shoulder pain is uncertain. Atrophy is less common but is associated with less severe shoulder pain.

Congenital and acquired brain injury. 3. Spectrum of the acquired brain injury population.

UNLABELLED: This self-directed learning module highlights the subpopulations of traumatic brain injury (TBI) that are treated by the rehabilitation practitioner. It is part of the chapter on TBI in the self-directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation. Specifically, this article focuses on the management of patients with mild TBI, children, and individuals with acquired brain injury from other etiologies, such as anoxic events or neoplastic lesions. The clinical spectrum of TBI, from the most severe presentation to the mildest, requires similar clinical skills to evaluate and manage. OVERALL ARTICLE OBJECTIVE: To describe the spectrum of brain injury populations based on age, severity, and etiology.

Congenital and acquired brain injury. 5. Emerging concepts in prognostication, evaluation, and treatment.

UNLABELLED: This self-directed learning module describes recent developments in the field of traumatic brain injury (TBI) rehabilitation. In particular, it focuses on the implications of recent technological advances for evaluation, prognostication, and treatment. It is part of the chapter on TBI medicine in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation. This article specifically focuses on neuroplasticity and its implications for rehabilitation interventions, the role of innovative neuroimaging modalities, improvements in our ability to prognosticate made possible by newer technologies, technologically based enhancement of motor rehabilitation, and the role of alternative and complementary medicine in TBI rehabilitation. OVERALL ARTICLE OBJECTIVE: To describe recent advances in our ability to evaluate, prognosticate, and treat traumatic brain injury.

Congenital and acquired brain injury. 4. Outpatient and community reintegration.

UNLABELLED: This self-directed learning module highlights the rehabilitation aspects of care for people with traumatic brain injury (TBI) after the acute phase. It focuses on issues important to community reentry, outpatient care, and return to work. It is part of the chapter on TBI medicine in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation. This article specifically focuses on the formulation of rehabilitation plans to address the issues of cognitive dysfunction, behavioral disturbances, and community reintegration. Topics covered include pharmacologic and nonpharmacologic approaches to cognitive and affective disorders, intimacy, social isolation, mobility, and return to work. Finally, the critical issues of legal competency and obtaining informed consent in the population with cognitive impairment are discussed. OVERALL ARTICLE OBJECTIVE: To summarize the issues that affect outpatient care, independence, and community reentry after traumatic brain injury.

Congenital and acquired brain injury. 1. Epidemiology, pathophysiology, prognostication, innovative treatments, and prevention.

UNLABELLED: This self-directed learning module reviews the current epidemiology of traumatic brain injury (TBI), its pathophysiology, prognostication after injury, currently available innovative early approaches to diagnosis and treatment, and effective methods of prevention. It is intended to provide the rehabilitation clinician with current knowledge to accurately inform patients, families, significant others, referring physicians, and payers and to aid in clinical decision making while caring for patients after TBI. OVERALL ARTICLE OBJECTIVE: To describe current knowledge in traumatic brain injury epidemiology, pathophysiology, prognostication, acute treatment, and prevention.

Congenital and acquired brain injury. 2. Medical rehabilitation in acute and subacute settings.

UNLABELLED: This self-directed learning module reviews common clinical problems and issues pertaining to early management of persons with traumatic brain injury (TBI). It is part of the study guide on brain injury medicine in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation. Acute TBI is frequently complicated by agitation, dystonia, and numerous orthopedic and neurologic comorbidities, often causing a decrement in function, which requires careful assessment and treatment. Individuals with acute brain injury typically receive rehabilitation in a setting determined by numerous factors, including medical stability and tolerance to rehabilitation interventions. OVERALL ARTICLE OBJECTIVES: To describe (a) common traumatic brain injury-related comorbidities and treatment strategies, (b) potential causes of declining patient performance, and (c) appropriate settings for rehabilitation interventions.

The Transformation of the Rehabilitation Paradigm Across the Continuum of Care.

As healthcare continues to evolve, there are changes in the delivery of care for patients with severe neurologic injuries. Although the acute hospital stay is shortening, physiatrists can play a key role in preparing patients for rehabilitation, minimizing longer-term complications and helping to determine the most appropriate paths for further treatment. Inpatient rehabilitation facilities (IRFs) continue to be an important part of the care continuum for patients with severe injuries, but the role of IRFs has also evolved as patients have been admitted with increasing medical and neurologic complexity and length of stay continues to be reduced. Skilled nursing facilities and subacute facilities continue to evolve, in part to fill the gaps that have developed for patients who are "not yet ready for rehabilitation" and for those whose recovery trajectory has been deemed too slow for IRF. Outpatient care is also changing, in part due to the availability of new rehabilitation interventions as highlighted in other sections of the supplement. Furthermore, telemedicine will provide additional options for expanding specialized care beyond prior geographical limitations. Physiatrists need to be aware of these ongoing changes and the roles that they can play outside of the traditional IRF model of care. This article will focus on the innovations in healthcare delivery and opportunities to maximize outcomes in the current and future models of care.