The use of robotics in rehabilitation medicine has become more popular due to the advantages it offers to the patients and the providers. Wearable robotic exoskeletons (REs) are approved by the Federal Drug Administration (FDA) for rehabilitation following spinal cord injury, CVA (cerebrovascular accident or stroke), and most recently acquired brain injury, inclusive of Traumatic Brain Injury (TBI, Globe Newswire, 2020). In addition, the RE can assist in repetitive task completion in increased doses (e.g., more steps per training). However, patients must meet strict requirements for RE use to ensure their safety (Palermo et al., 2017). All available REs currently in the market have weight and height requirements. Similarly, bone mineral density is a metric for eligibility to reduce fracture risk while using the device (Asselin et al., 2016). Provider recommendations and patient preferences also affect the decision to incorporate a RE in a patient rehabilitation program. While some studies in patients with spinal cord injury and CVA demonstrate benefits from the use of REs, additional evidence for disorders that cause gait and mobility problems such as traumatic brain injury (TBI) are still necessary (Hesse and Werner, 2009; Dijkers et al., 2019). Hence small studies with limited power, as presented herein, are a step forward in evidence toward generating future hypotheses and advancing the field.

The beneficial use of RE following a CVA has been established in the field. The first studies that examined the acceptance of robotics in patients after CVA started in the nineties (Dijkers et al., 1991). Consensus suggests that robotic-assisted gait training in patients after suffering a CVA is more likely to recover independent walking than those who did not use the robotic devices (Mehrholz et al., 2017; Bruni et al., 2018; Nolan et al., 2020). Studies also suggest that the use of robotics in rehabilitation could result in motor skills improvement and transfer into other daily living domains that require similar activities (Fasoli and Adans-Dester, 2019), hence improving cognitive domains. The time from CVA occurrence to the initiation of rehabilitation is critical for determining the patient's functional recovery degree. Multiple studies suggest that early initiation of rehabilitation results in improved long-term outcomes since most of the patient's recovery after a CVA occurs during the initial first 6 months (Kwakkel et al., 2004; Langhorne et al., 2011). Of importance in our patient population is the over indexing in Type 2 diabetes. Prior studies have identified diabetes as a predictive factor for patients' functional progress after a CVA, independent from other comorbidities including cardiovascular disease (Tziomalos, 2014; Wang et al., 2014). Moreover, patients with type 2 diabetes have twice the risk of suffering from an ischemic CVA than non-diabetics (Sarwar N, 2010) rendering diabetes an important variable in CVA rehabilitation.

Motor and ambulation deficits, which may resemble those presented in CVA, are frequently observed in patients with severe to moderate TBI (Williams et al., 2015). According to the Centers for Disease Control, ~3.2–5.3 million people are living with a TBI-related disability in the United States (Centers for Disease Control Prevention, 2019), constituting one of the leading causes of disability across the nation. TBIs are most frequently observed after motor vehicle accidents and falls (Centers for Disease Control and Prevention, 2015; National Spinal Cord Injury Statistical Center, 2019). Mortality due to TBI has significantly decreased in the United States (from 2006 to 2014, Centers for Disease Control and Prevention, 2015) suggestive of the positive impact from rehabilitation services. Similar to CVA, early rehabilitation intervention following TBI has been shown to produce improvements in post-TBI symptomathology (Parrington et al., 2020). Unfortunately, the data on the use of RE on patients with TBI is limited due to its later approval by the FDA for this condition, as compared to CVA. A recent case report of a young adult who suffered TBI, which resulted in right-side hemiplegia, revealed that RE's use during a 4-week inpatient program significantly improved motor functional independence measure (FIM) score from admission to discharge (Nolan et al., 2018). Moreover, using the RE in a patient with TBI showed increased brain cortical activity at the prefrontal, premotor, and motor cortices at follow up compared to no-RE walking (Karunakaran et al., 2020), suggesting that robotic-assisted gait may produce different cortical brain mechanisms activation.

The United States' Rio Grande Valley, along the Texas-Mexico border, is comprised of ~90% Hispanic ethnicity and 90% Mexican descent. This region is characterized by socioeconomic factors that have been demonstrated to affect clinical outcomes. Such factors include non-insured and underinsured status, a tremendous shortage in primary care providers (medically underserved), and over 30% of the population living in poverty (UT Health–School of Public Health Brownsville, 2018). Thirty percent of the Rio Grande Valley residents have diabetes, compared to 12.3% nationwide (Millard et al., 2017), rendering this region a unique site to study the impact of this over prevalent disease on CVA and TBI rehabilitation outcomes.

Inspired by the unique characteristics of our patient population, this study's main goal was to determine which factors predict the improvement in functional independence measure (FIM) score after using RE rehabilitation in a population of patients with CVA or TBI, with the goal of producing preliminary data that could inform future implementation and design of larger clinical trials. Within the model, we included Type 2 diabetes as a variable and other previously reported predictive factors for functional improvement in rehabilitation after CVA (Wang et al., 2014). The model was based on the rationale that TBI and CVA are both acquired brain injuries that produce related neurofunctional impairments (Giles, 2010; Capizzi et al., 2020), both of which could benefit from RE rehabilitation training. The rationale for comparing TBI and CVA is based on a previous study showing very similar linear improvements in motor functioning during conventional rehabilitation (Bode and Heinemann, 2002). Therefore, determining if RE rehabilitation modifies the functional progression in TBI as compared to CVA has the potential of increasing its use for TBI and expand the research done in this area.

The matching algorithm yielded a final sample size of 36 patients. Demographic characteristics and clinical measures for the patients are summarized by injury type (TBI vs. CVA) in Table 1, and diabetic status in Table 2. The TBI and CVA patients showed no significant differences in demographic and clinical measures. Specifically the admission motor FIM scores and the change in motor FIM were similar for patients with a CVA and TBI (Figure 2A). The diabetic population was found to be significantly older than the non-diabetic population (65.06 vs. 49.17; p = 0.01). However, the admission and motor FIM scores were similar between diabetic and non-diabetic status (Figure 2B). The diabetic population took significantly fewer days from injury to the start of rehabilitation (15.06 vs. 36.5; p = 0.03). Significant zero-order Pearson correlations were identified for seven pairs of metrics: admission motor FIM score, motor FIM change, diabetic status, sex (male), patient age, days to start rehabilitation, type of injury (TBI), GCS and total number of steps taken (See Table 3).

The multivariate linear regression assessed predictors for discharge motor FIM and found admission motor FIM score and total robotic steps to be statistically significant predictors. For each point scored higher on the admission motor FIM, the discharge FIM was found to increase by 1.19 (p < 0.001; 95% CI 0.89–1.49). For every 1,000 steps taken in the RE, a three-point increase in discharge motor FIM was found (p < 0.04; 95% CI 0.18–6.6). Our regression modeled 65% of the variance (adj R² = 0.62) and was found to be statistically significant [F_(2,33) = 33.41; p < 0.001].

A second multivariate linear regression modeled predictors for admission motor FIM score. The days from injury to the start of rehabilitation, diabetic status, as well as the interaction term for these variables were found to be statistically significant [F_(3,32) = 4.17; p = 0.008]. After computing the partial derivatives and controlling for diabetic status, we found waiting an additional day to start rehabilitation within the diabetic cohort correlated with a −0.71 point drop in admission motor FIM score (p = 0.001; 95% CI −1.14–0.29). We found no significant correlation for diabetic status, nor days to start rehabilitation within the non-diabetic cohort. Our findings suggest that waiting 10 days to start rehabilitation as a diabetic patient, even when using a RE in the rehabilitation process, will correlate with a 7.1 point drop in admission FIM score.

We present a comparative analysis amongst patients with a history of CVA and TBI, showing similar post RE rehabilitation outcomes regardless of the injury type. Both CVA and TBI are non-progressive central nervous system condition that have very similar impairments (DiRocco, 1995). Because of the similarity in impairment between CVA and TBI, the use of RE for TBI patients was conceivable. While it is recognized that additional controlled clinical trials are needed for exoskeleton rehabilitation in TBI, this preliminary study illustrates similar, positive outcomes in functionality to those patients treated with the exoskeleton which had a CVA. To our knowledge, this is the first study reporting diabetic status, time to rehabilitation and steps taken in the exoskeleton as predictive factors of functional outcomes in a cohort of Hispanic patients. This study is one of the first showing that the type of acquired brain injury is not a determinant of motor functional outcome after RE use.

Patients within the TBI group were significantly younger than patients in the CVA group. There are several possible explanations for this observation. First, more than 80% of all CVA incidences across the nation occur in people 65 years and older (Blackwell and Villarroel, 2018), in comparison to TBI for which two of the high risk groups are young children (age 0 to 4) and older adolescents (age 15–19; Centers for Disease Control and Prevention, 2015). Second, the use of RE required specific physical (e.g., height and weight) characteristics as well as physiological (e.g., bone density) to prevent injuries. It is well-documented that older patients (>50 years of age) are at higher risk of osteoporosis (Lane, 2006), which is one of the main contraindications for the use of the exoskeleton, excluding them as potential users. Patient-preference is held at the highest priority when identifying eligible users. Anecdotal evidence from our hospital suggests that older patients are less likely to prefer RE rehabilitation, while younger patients are more eager to engage in the use of bionics and robotics, which could partially explain the age difference in our study cohort. Additional studies are needed to explore the generational gap in rehabilitation preferences, especially for the use of robotic devices.

Patients who suffer TBI, even when mild, could end up having impairments up to 1 year post injury (Nelson et al., 2019). Cognitive impairments after TBI could have even a longer sequelae, lasting up to 4 years, as previously reported (Theadom et al., 2019). The sequelae post-TBI that affects cognitive function is known as post-concussive syndrome (Permenter et al., 2020). To minimize its impact in patient's quality of life, rehabilitation approaches that promote neuroplastic changes in the brain, such as those produced by exoskeleton training, could result in an overall increase in functional domains for the patient after a TBI or CVA (Berger et al., 2019). While the overall improvement in cognitive FIM scores in the current cohort of patients was small, a 1 point increase in FIM scores corresponds to an increase of 1.08 more likely to be discharged to the home rather than to institutionalized care (Thorpe et al., 2018); hence decreasing healthcare cost on the long-term.

The use of robotic interventions in patients with TBI was approved by the FDA at a later time point than for CVA. This delay had in part contributed to a reduced number of studies using RE for TBI. A systematic review from 2011 reported 10 randomized controlled trials for the use of robotic devices in CVA rehabilitation, but none for TBI (Tomida et al., 2019). However, recent reports indicate increased use of robotic rehabilitation following TBI; for example, to quantify the degree of impairment (Logan et al., 2018), improve cognitive function (Maggio et al., 2020), to support treadmill training (Esquenazi et al., 2013), to measure brain activity while having robotic gait training (Lapitskaya et al., 2011), and to increase gait velocity (Esquenazi et al., 2017). While the outcomes of these studies are mixed due to the differences in patient population, training techniques used, and type of equipment, it is promising that the field is recognizing how robotics present with a novel opportunity to improve quality of life in patients with TBI.

A recent study exploring the longitudinal effects of TBI revealed that higher total health burden was associated with poorer functional motor and cognitive trajectories (Kumar et al., 2020). To decrease the negative impact that TBI might have, it is hypothesized the continuous use of RE as a rehabilitation device in our hospital will significantly continue to improve functional outcomes. Since the intervention with RE revealed similar outcomes to the CVA patient cohort, even with small sample size, it is foreseen that many more patients eligible to use exoskeleton rehabilitation devices will greatly benefit from this therapeutic modality.

Diabetes is a modifiable factor strongly associated with CVA of both the ischemic and hemorrhagic type (O'Donnell et al., 2010; Lee et al., 2012). Unfortunately, the risk for CVA in diabetic patients is higher in the younger population, specifically before the age of 55 years (Khoury et al., 2013). In addition, people with diabetes also tend to suffer from other comorbidities such as hypertension and high cholesterol. A previous review on the topic suggested that stroke outcomes in individuals with diabetes depend on a prompt and persistent implementation of therapies, for the successful recovery of the individual (Chen et al., 2017). When it comes to TBI, diabetes is a well-known complication of patients in the intensive care units, and is predictive of increased mortality and poorer outcomes (Gempeler et al., 2020). Additionally, detrimental effects of pre-existing diabetes have been reported in TBI using an animal model, showing increased brain contusion volume and higher inflammatory markers (Tatara et al., 2020). In light of these previous findings, we propose that including RE rehabilitation for patients who suffer either TBI or CVA in a prompt fashion, could provide increased benefits when done in parallel with strict glucose control measures.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving human participants were reviewed and approved by DHR Health Institute for Research and Development. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.

LT and MA conceptualized the original research idea and wrote the original research protocol. AM collected and verified all data used in the project. PR analyzed the data and prepared figures, methods, and results sections. AT-R supervised data analysis and wrote the first version of the manuscript with LT. All authors contributed to the final edits of the document and approved the current version.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.