Subacute Phase Research Articles

Post-stroke treatment - use of virtual reality as aid in motor rehabilitation

This study describes the use of Virtual Reality (VR) therapy in the rehabilitation of patients after suffering from a cerebrovascular accident (CVA) who had motor sequelae. Several studies were presented showing that the use of VR as a rehabilitation tool can bring significant benefits in improving the motor function of patients. Introducing different elements into therapy, such as task-specific practice, explicit feedback, increasing difficulty, implicit feedback, variable practice, and mechanisms to promote use of the paretic limb, can enhance clinical benefits. Studies in patients in the subacute and chronic phases of stroke were presented, showing that VR therapy combined with other therapies can bring about significant improvements in motor function, manual skill and other measures related to the performance of upper limb activities.

A comprehensive characterization of cognitive performance, clinical symptoms, and cortical activity following mild traumatic brain injury (mTBI)

Objective The objective of this study was to investigate clinical symptoms, cognitive performance and cortical activity following mild traumatic brain injury (mTBI). Methods We recruited 30 individuals in the sub-acute phase post mTBI and 28 healthy controls with no history of head injury and compared these groups on clinical, cognitive and cortical activity measures. Measures of cortical activity included; resting state electroencephalography (EEG), task related EEG and combined transcranial magnetic stimulation with electroencephalography (TMS-EEG). Primary analyses investigated clinical, cognitive and cortical activity differences between groups. Exploratory analyses investigated the relationships between these measures. Results At 4 weeks’ post injury, mTBI participants exhibited significantly greater post concussive and clinical symptoms compared to controls; as well as reduced cognitive performance on verbal learning and working memory measures. mTBI participants demonstrated alterations in cortical activity while at rest and in response to stimulation with TMS. Conclusions The present study comprehensively characterized the multidimensional effect of mTBI in the sub-acute phase post injury, showing a broad range of differences compared to non-mTBI participants. Further research is needed to explore the relationship between these pathophysiologies and clinical/cognitive symptoms in mTBI.

Neurophysiological signatures of mild traumatic brain injury in the acute and subacute phase

BackgroundMild traumatic brain injury (mTBI) affects 48 million people annually, with up to 30% experiencing long-term complaints such as fatigue, blurred vision, and poor concentration. Assessing neurophysiological features related to visual attention and outcome measures aids in understanding clinical symptoms and prognostication.MethodsWe recorded EEG and eye movements in mTBI patients during a computerized task performed in the acute (< 24 h, TBI-A) and subacute phase (4–6 weeks thereafter). We estimated the posterior dominant rhythm, reaction times (RTs), fixation duration, and event-related potentials (ERPs). Clinical outcome measures were assessed using the Head Injury Symptom Checklist (HISC) and the Extended Glasgow Outcome Scale (GOSE) at 6 months post-injury. Similar analyses were performed in an age-matched control group (measured once). Linear mixed effect modeling was used to examine group differences and temporal changes within the mTBI group.ResultsTwenty-nine patients were included in the acute phase, 30 in the subacute phase, and 19 controls. RTs and fixation duration were longer in mTBI patients compared to controls (p < 0.05), but not between TBI-A and TBI-S (p < 0.05). The frequency of the posterior dominant rhythm was significantly slower in TBI-A (0.6 Hz, p < 0.05) than TBI-S. ERP mean amplitude was significantly lower in mTBI patients than in controls. Neurophysiological features did not significantly relate to clinical outcome measures.ConclusionmTBI patients demonstrate impaired processing speed and stimulus evaluation compared to controls, persisting up to 6 weeks after injury. Neurophysiological features in mTBI can assist in determining the extent and temporal progression of recovery.Graphical abstract

Propofol anesthesia improves stroke outcomes over isoflurane anesthesia-a longitudinal multiparametric MRI study in a rodent model of transient middle cerebral artery occlusion.

General anesthesia is routinely used in endovascular thrombectomy procedures, for which volatile gas and/or intravenous propofol are recommended. Emerging evidence suggests propofol may have superior effects on disability and/or mortality rates, but a mode-of-action underlying these class-specific effects remains unknown. Here, a moderate isoflurane or propofol dosage on experimental stroke outcomes was retrospectively compared using serial multiparametric MRI and behavioral testing. Adult male rats (N = 26) were subjected to 90-min filament-induced transient middle cerebral artery occlusion. Diffusion-, T2- and perfusion-weighted MRI was performed during occlusion, 0.5 h after recanalization, and four days into the subacute phase. Sequels of ischemic damage-blood-brain barrier integrity, cerebrovascular reactivity and sensorimotor functioning-were assessed after four days. While size and severity of ischemia was comparable between groups during occlusion, isoflurane anesthesia was associated with larger lesion sizes and worsened sensorimotor functioning at follow-up. MRI markers indicated that cytotoxic edema persisted locally in the isoflurane group early after recanalization, coinciding with burgeoning vasogenic edema. At follow-up, sequels of ischemia were further aggravated in the post-ischemic lesion, manifesting as increased blood-brain barrier leakage, cerebrovascular paralysis and cerebral hyperperfusion. These findings shed new light on how isoflurane, and possibly similar volatile agents, associate with persisting injurious processes after recanalization that contribute to suboptimal treatment outcome.

Integrated Machine Learning Approach for the Early Prediction of Pressure Ulcers in Spinal Cord Injury Patients.

(1) Background: Pressure ulcers (PUs) substantially impact the quality of life of spinal cord injury (SCI) patients and require prompt intervention. This study used machine learning (ML) techniques to develop advanced predictive models for the occurrence of PUs in patients with SCI. (2) Methods: By analyzing the medical records of 539 patients with SCI, we observed a 35% incidence of PUs during hospitalization. Our analysis included 139 variables, including baseline characteristics, neurological status (International Standards for Neurological Classification of Spinal Cord Injury [ISNCSCI]), functional ability (Korean version of the Modified Barthel Index [K-MBI] and Functional Independence Measure [FIM]), and laboratory data. We used a variety of ML methods-a graph neural network (GNN), a deep neural network (DNN), a linear support vector machine (SVM_linear), a support vector machine with radial basis function kernel (SVM_RBF), K-nearest neighbors (KNN), a random forest (RF), and logistic regression (LR)-focusing on an integrative analysis of laboratory, neurological, and functional data. (3) Results: The SVM_linear algorithm using these composite data showed superior predictive ability (area under the receiver operating characteristic curve (AUC) = 0.904, accuracy = 0.944), as demonstrated by a 5-fold cross-validation. The critical discriminators of PU development were identified based on limb functional status and laboratory markers of inflammation. External validation highlighted the challenges of model generalization and provided a direction for future research. (4) Conclusions: Our study highlights the importance of a comprehensive, multidimensional data approach for the effective prediction of PUs in patients with SCI, especially in the acute and subacute phases. The proposed ML models show potential for the early detection and prevention of PUs, thus contributing substantially to improving patient care in clinical settings.

Lack of gut microbiome recovery with spinal cord injury rehabilitation

ABSTRACT Spinal cord injury (SCI) is a devastating event that significantly changes daily function and quality of life and is linked to bowel and bladder dysfunction and frequent antibiotic treatment. We aimed to study the composition of the gut microbiome in individuals with SCI during the initial sub-acute rehabilitation process and during the chronic phase of the injury. This study included 100 fecal samples from 63 participants (Median age 40 years, 94% males): 13 cases with SCI in the sub-acute phase with 50 longitudinal samples, 18 cases with chronic SCI, and 32 age and gender-matched controls. We show, using complementary methods, that the time from the injury was a dominant factor linked with gut microbiome composition. Surprisingly, we demonstrated a lack of gut microbial recovery during rehabilitation during the sub-acute phase, with further deviation from the non-SCI control group in the chronic ambulatory SCI group. To generalize the results, we were able to show significant similarity of the signal when comparing to a previous cohort with SCI, to subjects from the American Gut Project who reported low physical activity, and to subjects from another population-based cohort who reported less normal stool consistency. Restoration of the microbiome composition may be another desirable measure for SCI recovery in the future, but further research is needed to test whether such restoration is associated with improved neurological outcomes and quality of life.

The presence of anhedonia in individuals with subacute and chronic stroke: an exploratory cohort study.

Anhedonia refers to the diminished capacity to experience pleasure. It has been described both as a symptom of depression and an enduring behavioral trait that contributes its development. Specifically, in stroke patients, anhedonia has been closely linked to depression, resulting in reduced sensitivity to everyday pleasures and intrinsic motivation to engage in rehabilitation programs and maintain a healthy active lifestyle. This condition may hinder patients' recovery, diminishing their autonomy, functioning, and quality of life. We aimed to explore the prevalence and level of anhedonia and those variables that might be associated in patients with both ischemic and hemorrhagic stroke at subacute and chronic phases of the disease. We conducted an exploratory cohort study with a sample of 125 patients with subacute and chronic stroke presenting upper-limb motor deficits. We measured participants' level of anhedonia with four items from the Beck Depression Inventory-II that describe the symptoms of this condition: loss of pleasure, loss of interest, loss of energy, and loss of interest in sex. We also collected demographic and clinical information and evaluated motor and cognitive functions as well as levels of depression, apathy, and various mood states. The results were compared to a sample of 71 healthy participants of similar age, sex, and level of education. Stroke patients demonstrated a significantly higher prevalence (18.5-19.7%) and level of anhedonia compared to the healthy controls (4.3%), regardless of stroke phase, level of motor impairment, and other clinical variables. Furthermore, post-stroke anhedonia was associated with lower levels of motivation and higher levels of negative mood states such as fatigue and anger in the long term. Importantly, anhedonia level was superior in stroke patients than in healthy controls while controlling for confounding effects of related emotional conditions. This study provides novel evidence on the prevalence, level and factors related to anhedonia post-stroke. We emphasize the importance of assessing and treating anhedonia in this population, as well as conducting large-scale cohort and longitudinal studies to test its influence on long-term functional and emotional recovery.

Abstract TP91: Baseline Comorbidities and Functional Status Are Associated With Subacute Post-Stroke Aphasia Severity

Speech or language changes are just one of the critical stroke warning signs. While symptoms may resolve with treatment, there are individuals for whom aphasia persists. The purpose of this study was to develop a better understanding of which factors are associated with aphasia status in the first six months after left hemisphere stroke to aid clinicians in discussing prognosis and preparing patients for what to expect in recovery. The sample consisted of a subset of individuals from a large, ongoing, federally funded, observational study of speech and language profiles, for whom an NIH Stroke Scale (NIHSS) total score was available (N=59, 35 female, mean age at stroke= 65 years, range = 38-92). We analyzed the complex interaction between the baseline medical (reperfusion/surgical intervention; comorbid hypertension, atrial fibrillation, high cholesterol, diabetes), functional (NIHSS total score), and demographic (age, sex, race) characteristics associated with the Quick Aphasia Battery (QAB) overall score, a measure of aphasia severity, using multiple linear regression. An additional one-way ANOVA was conducted to examine the relationship between baseline (NIHSS language subtest rating) and subacute aphasia status. The multiple linear model of the relationship between baseline factors and subacute aphasia severity was significant (F(114, 43)=1.956, p=0.047), though it accounted for less than 40% of the variance in aphasia severity scores. Of the factors included in the model, hypertension (F(1, 43)=4.513, p=0.039) and NIHSS total score (F(1, 43), p&lt;0.001) were significant. In our secondary analysis, the one-way ANOVA was significant (F(3, 50)=6.106, p=0.001) with individuals rated as normal having, on average, a 3 point difference (p=.001) in overall QAB score from those rated as mute at baseline. This study examined the association between baseline comorbidities and functional status in adults with subacute post-stroke aphasia. We noted that hypertension and baseline NIHSS total score are significantly related to aphasia severity as measured by the QAB overall score in the subacute phase. Although much variation exists, our results may indicate that those with unimpaired language at baseline tend to perform better later in recovery.

Abstract TP93: A Bayesian Hierarchical Time Series Model to Forecast Patient Recovery Outcomes After an Acute Stroke When Activity Monitor Data is Incomplete

Background: Activity monitor data is a useful tool in clinical trials to monitor patient recovery after stroke. These data offer important information on activity, sedentary and sleep behaviors throughout recovery. However, not all participants wear activity monitors, or their activity data may be incomplete. The purpose of this study was to develop a model-based approach to obtain individual patient-level longitudinal forecast estimates of activity and sleep behaviors for both those with and without complete activity data. Methods: Participants wore an ActivPal (steps/day) and Actigraph (total sleep/day) monitors for 3-7 days at 10-60-90 days post stroke. We developed a Bayesian hierarchical time series model to forecast daily steps and sleep time by participant. We included a logistic growth curve in which we use predictors comprising age, sex, race, marital status, smoking, BMI, cognition, gait speed, depression, self-reported sleep, and patients’ previous time trends to forecast patient specific future time trends during the first 90 days following stroke. Results: Data were collected on a total sample of 114 participants. Out of the 114 participants, 73 participants had recorded sleep data, and 76 participants had step data reported, which are not mutually exclusive groups. Out of 114 total participants, 41 participants did not have any sleep or step data recorded. We obtained patient-specific time trends for both patients with and without monitor data. To assess model predictive performance, we compared predicted estimates to observed data using a validation study and found that on average, there was a difference of 0.52 daily steps (counts). Additionally, on average, there was a difference of 0.46 between observed and estimated daily sleep count (minutes). Discussion: The contribution of our study is a model-based approach to accurately predict patient-specific longitudinal step and sleep behaviors based on predictor variables and previous time trends for patients in the subacute stroke recovery phase. Our approach may be extended to other applications using activity monitor data. A limitation of this study is the increased uncertainty surrounding forecast estimates for periods/days without data, which will be addressed in future work.

Movement disorders following mechanical thrombectomy resulting in ischemic lesions of the basal ganglia: An emerging clinical entity.

Post-stroke movement disorders (PMDs) following ischemic lesions of the basal ganglia (BG) are a known entity, but data regarding their incidence are lacking. Ischemic strokes secondary to proximal middle cerebral artery (MCA) occlusion treated with thrombectomy represent a model of selective damage to the BG. The aim of this study was to assess the prevalence and features of movement disorders after selective BG ischemia in patients with successfully reperfused acute ischemic stroke (AIS). We enrolled 64 consecutive subjects with AIS due to proximal MCA occlusion treated with thrombectomy. Patients were clinically evaluated by a movement disorders specialist for PMDs onset at baseline, and after 6 and 12 months. None of the patients showed an identifiable movement disorder in the subacute phase of the stroke. At 6 and 12 months, respectively, 7/25 (28%) and 7/13 (53.8%) evaluated patients developed PMDs. The clinical spectrum of PMDs encompassed parkinsonism, dystonia and chorea, either isolated or combined. In most patients, symptoms were contralateral to the lesion, although a subset of patients presented with bilateral involvement and prominent axial signs. Post-stroke movement disorders are not uncommon in long-term follow-up of successfully reperfused AIS. Follow-up conducted by a multidisciplinary team is strongly advisable in patients with selective lesions of the BG after AIS, even if asymptomatic at discharge.

Sleep and motor learning in stroke (SMiLES): a longitudinal study investigating sleep-dependent consolidation of motor sequence learning in the context of recovery after stroke

IntroductionThere is growing evidence that sleep is disrupted after stroke, with worse sleep relating to poorer motor outcomes. It is also widely acknowledged that consolidation of motor learning, a critical...

Alleviating sleep disturbances and modulating neuronal activity after ischemia: Evidence for the benefits of zolpidem in stroke recovery.

Sleep disorders are prevalent among stroke survivors and impede stroke recovery, yet they are still insufficiently considered in the management of stroke patients, and the mechanisms by which they occur remain unclear. There is evidence that boosting phasic GABA signaling with zolpidem during the repair phase improves stroke recovery by enhancing neural plasticity; however, as a non-benzodiazepine hypnotic, the effects of zolpidem on post-stroke sleep disorders remain unclear. Transient ischemic stroke in male rats was induced with a 30-minute middle cerebral artery occlusion. Zolpidem or vehicle was intraperitoneally delivered once daily from 2 to 7 days after the stroke, and the electroencephalogram and electromyogram were recorded simultaneously. At 24 h after ischemia, c-Fos immunostaining was used to assess the effect of transient ischemic stroke and acute zolpidem treatment on neuronal activity. In addition to the effects on reducing brain damage and mitigating behavioral deficits, repeated zolpidem treatment during the subacute phase of stroke quickly ameliorated circadian rhythm disruption, alleviated sleep fragmentation, and increased sleep depth in ischemic rats. Immunohistochemical staining showed that in contrast to robust activation in para-infarct and some remote areas by 24 h after the onset of focal ischemia, the activity of the ipsilateral suprachiasmatic nucleus, the biological rhythm center, was strongly suppressed. A single dose of zolpidem significantly upregulated c-Fos expression in the ipsilateral suprachiasmatic nucleus to levels comparable to the contralateral side. Stroke leads to suprachiasmatic nucleus dysfunction. Zolpidem restores suprachiasmatic nucleus activity and effectively alleviates post-stroke sleep disturbances, indicating its potential to promote stroke recovery.

Abstract WMP115: Rapid Vascular Complement Activation: A Key Driver of Blood-Brain Barrier Disruption in Ischemic Stroke With Acute Hyperglycemia

Background: Acute hyperglycemia, which occurs in over 40% of ischemic stroke patients irrespective of pre-existing diabetes, exacerbates stroke injury. Understanding its mechanisms is vital for innovative treatments. Here we investigate the role of complement in hyperglycemia-exacerbated damage after stroke. Method: Male C57/BL6 mice (10-11 weeks) underwent 30-min suture-induced middle cerebral artery occlusion followed by reperfusion, resembling clinical thrombectomy. Acute hyperglycemia was induced 10 min pre-stroke via glucose injection. Mice were sacrificed at 4.5h and 24h post-stroke to analyze brain swelling, blood-brain barrier (BBB) leakage and hemorrhagic transformation (HT). Mortality, neurological deficits, and motor-sensory functions were assessed at 14 days post-stroke. Complement activation was visualized via C3d immunostaining. Complement C3's role was examined using knock-out mice and the targeted complement inhibitor CR2-Crry fusion protein. Result: Hyperglycemia rapidly worsens BBB leakage (p&lt;0.0001), brain swelling (p&lt;0.05), and HT (p&lt;0.0001) at 4.5 hr after stroke. Hyperglycemic stroke mice exhibit higher mortality (100% vs 25%, p=0.0008), body weight loss, and behavior impairment at the sub-acute phase compared to normoglycemic mice. Notably, acute hyperglycemia rapidly increased plasma C3 levels at 1hr after stroke (p&lt;0.01), accompanied by rapid and time-dependent activation of C3 in ischemic brain vessels, as marked by increased vascular C3d; and this co-localized with autoantibody (IgM/IgG) vessel buildup and vessel leakage. Additionally, C3d levels positively correlated with brain swelling and HT (p&lt;0.01). Vascular C3d and leakage into parenchyma were markedly reduced in the absence of reperfusion. Blocking complement via C3 knock-out or post-reperfusion systemic injection of C3 inhibitor CR2-Crry mitigates hyperglycemia's detrimental effects, including BBB leakage. Conclusion: Rapid vascular activation of complement C3 is a significant driver of hyperglycemic-exacerbated pathology in experimental stroke. Inhibiting C3 activation could be a potential therapeutic approach to improve hyperglycemic stroke outcome.

Distinct patterns of cytokines, chemokines, and growth factors in synovial fluid after ACL injury in comparison to osteoarthritis.

This study analyzed knee synovial fluid after anterior cruciate ligament (ACL) tear and in osteoarthritis (OA) to test the hypotheses that concentrations of cytokines, chemokines, and growth factors differ (a) by diagnosis and (b) after ACL tear by time from injury and presence/absence of concomitant meniscus tear. Synovial fluid samples were collected from two groups, ACL tears (with or without meniscus tear) (N = 13) and Kellgren-Lawrence grade 3 and 4 OA (N = 16), undergoing clinically indicated aspiration of the knee joint. Multiple cytokines, chemokines, and growth factors were assessed using a multiplexed 45-protein panel. Comparisons were made for the concentrations of all molecules between ACL tear and OA patients, isolated versus combined ACL and meniscus tears, and categorized by time from injury: acute or early subacute (<15 days, N = 8) versus late subacute or chronic (>15 days and <3 months, N = 5). ACL tear patients have higher levels of six molecules (IL-4, IL-5, IL-13, PlGF-1, bNGF, TNF-α) in knee synovial fluid compared to OA patients. Isolated ACL tears express higher levels of IL-4, IL-13 and IFN-γ and lower levels of IL-7 than ACL tears with a concomitant meniscus tear. SDF-1α, PlGF-1, IL-1RA, HGF, bNGF, and BDNF levels are elevated immediately after injury and drop off significantly in the late subacute phase (after 15 days). Synovial fluid from knees with ACL tears have elevated metabolic activity compared to knees with OA. The cytokine profiles after ACL tears are influenced by the time from injury and the presence of meniscus tears. These findings offer valuable insights into the levels of cytokines, chemokines, and growth factors in the knee after ACL injury, information which may have important implications for the diagnosis, prognosis and treatment of this common pathology.

Long-term repetitive transcranial direct current stimulation in patients with disorders of consciousness: a preliminary study

ABSTRACT Objectives To investigate the effects of long-term repetitive transcranial direct current stimulation on patients with DOC in the subacute phase. Methods In a randomized, double-blind, controlled study, 33 patients were randomly assigned to the active or sham group, and 28 patients completed the study. Patients in the active group received anodal stimulation over the DLPFC, while patients in the sham group received placebo stimulation (20 min/day, 5 days/week, for 4 weeks). The level of consciousness among patients was assessed with the Coma Recovery Scale-Revised (CRS-R) at baseline and at the end of every week from the first to the fourth week. Results The CRS-R scores of both the active and sham groups showed a consistent increasing trend over time; however, the treatment effect of the active group was better than that of the sham group. In addition, there was a statistically significant difference in the total CRS-R score between the two groups at weeks 1, 2, 3 and 4. Moreover, 10 patients (71.4%) in the active group and 3 patients (21.4%) in the sham group were regarded as responders. Conclusion Long-term tDCS could improve the level of consciousness of patients with DOC in the subacute stage.

Does visuospatial neglect contribute to standing balance within the first 12 weeks post-stroke? A prospective longitudinal cohort study.

Visuospatial neglect (VSN) has been suggested to limit standing balance improvement post-stroke. However, studies investigating this association longitudinally by means of repeated within-subject measurements early post-stroke are lacking. This prospective longitudinal cohort study evaluates the longitudinal association of egocentric and allocentric VSN severity with 1) standing balance independence and 2) postural control and weight-bearing asymmetry (WBA) during quiet standing, in the first 12 weeks post-stroke. Thirty-six hemiplegic individuals after a first-ever unilateral stroke were evaluated at weeks 3, 5, 8 and 12 post-stroke. Egocentric and allocentric VSN severity were evaluated using the Broken Hearts Test. The standing unperturbed item of the Berg Balance Scale (BBS-s) was used to clinically evaluate standing independence. Posturographic measures included measures of postural control (mediolateral (ML)/anteroposterior (AP) net center-of-pressure velocities (COPvel)) and WBA during quiet standing. A linear mixed model was used to examine longitudinal associations between egocentric and allocentric VSN, and BBS-s, COPvel-ML, COPvel-AP and WBA within the first 12 weeks post-stroke. Egocentric (β = -0.08, 95%CI[-0.15;-0.01], P = .029) and allocentric VSN severity (β = -0.09, 95%CI[-0.15; -0.04], P = .002) were significant independent factors for BBS-s scores in the first 12 weeks post-stroke. Egocentric and allocentric VSN were no significant independent factors for COPvel-ML, COPvel-AP and WBA in the first 12 weeks post-stroke. Allocentric and egocentric VSN severity were significantly associated with decreased standing independence, but not impaired postural control or greater asymmetric weight-bearing, in the early subacute post-stroke phase. This may involve traditional VSN measures being not sensitive enough to detect fine-grained VSN deficits due to a ceiling effect between 5 and 8 weeks post-stroke, once the individual regains standing ability. Future studies may require more sensitive VSN measurements to detect such deficits. Trial registration Clinicaltrials.gov. unique identifier NCT05060458.

Serum GFAP, NfL, and tau concentrations are associated with worse neurobehavioral functioning following mild, moderate, and severe TBI: a cross-sectional multiple-cohort study.

The purpose of this study was to examine whether blood-based biomarkers associate with neurobehavioral functioning at three time points following traumatic brain injury (TBI). Participants were 328 United States service members and veterans (SMVs) prospectively enrolled in the Defense and Veterans Brain Injury Center-Traumatic Brain Injury Center of Excellence (DVBIC-TBICoE) 15-Year Longitudinal TBI Study, recruited into three groups: uncomplicated mild TBI (MTBI, n = 155); complicated mild, moderate, severe TBI combined (STBI, n = 97); non-injured controls (NIC, n = 76). Participants were further divided into three cohorts based on time since injury (≤12 months, 3-5 years, and 8-10 years). Participants completed the Minnesota Multiphasic Personality Inventory-2-Restructured Format (MMPI-2-RF) and underwent blood draw to measure serum concentrations of glial fibrillary acidic protein (GFAP), neurofilament light (NfL), and tau. A total of 11 MMPI-2-RF scales were examined (e.g., depression, anxiety, anger, somatic, cognitive symptoms). Stepwise hierarchical regression models were conducted within each group. Significant associations were found between biomarkers and MMPI-2-RF scales (all p < 0.05; R2Δ > 0.10). GFAP was inversely related to (a) neurological complaints in the MTBI group at ≤12 months, (b) demoralization, anger proneness in the STBI group at ≤12 months, and (c) head pain complaints in the STBI group at 8-10 years. NfL was (a) related to low positive emotions in the NIC group; and inversely related to (b) demoralization, somatic complaints, neurological complaints, cognitive complaints in the MTBI group at ≤12 months, (c) demoralization in the STBI group at ≤12 months, and (d) demoralization, head pain complaints, stress/worry in the STBI group at 3-5 years. In the STBI group, there were meaningful findings (R2Δ > 0.10) for tau, NFL, and GFAP that did not reach statistical significance. Results indicate worse scores on some MMPI-2-RF scales (e.g., depression, stress/worry, neurological and head pain complaints) were associated with lower concentrations of serum GFAP, NfL, and tau in the sub-acute and chronic phase of the recovery trajectory up to 5 years post-injury, with a reverse trend observed at 8-10 years. Longitudinal studies are needed to help elucidate any patterns of association between blood-based biomarkers and neurobehavioral outcome over the recovery trajectory following TBI.

ROCK2 regulates microglia proliferation and neuronal survival after traumatic brain injury

Traumatic brain injury (TBI) results in prolonged and non-resolving activation of microglia. Forced turnover of these cells during the acute phase of TBI aids recovery, but the cell-intrinsic pathways that underpin the pro-repair phenotype of these repopulating microglia remain unclear. Here, we show that selective targeting of ROCK2 with the small molecule inhibitor KD025 impairs the proliferative response of microglia after TBI as well as during genetically induced turnover of microglia. KD025 treatment abolished the substantial neuroprotective and cognitive benefits conferred by repopulating microglia, preventing these cells from replenishing the depleted niche during the early critical time window post-injury. Delaying KD025 treatment to the subacute phase of TBI allowed microglial repopulation to occur, but this did not enhance the benefits conferred by repopulating microglia. Taken together, our data indicate that ROCK2 mediates neuronal survival and microglial population dynamics after TBI, including the emergence of repopulating microglia with a pro-repair phenotype.

MoCA Domain-Specific Pattern of Cognitive Impairment in Stroke Patients Attending Intensive Inpatient Rehabilitation: A Prospective Study.

A domain-specific perspective to cognitive functioning in stroke patients may predict their cognitive recovery over time and target stroke rehabilitation intervention. However, data about domain-specific cognitive impairment after stroke are still scarce. This study prospectively investigated the domain-specific pattern of cognitive impairments, using the classification proposed by the Montreal Cognitive Assessment (MoCA), in a cohort of 49 stroke patients at admission (T0), discharge (T1), and six-month follow-up (T2) from subacute intensive rehabilitation. The predictive value of T0 cognitive domains cognitive impairment at T1 and T2 was also investigated. Patients' cognitive functioning at T0, T1, and T2 was assessed through the MoCA domains for executive functioning, attention, language, visuospatial, orientation, and memory. Different evolutionary trends of cognitive domain impairments emerged across time-points. Patients' impairments in all domains decreased from T0 to T1. Attention and executive impairments decreased from T0 to T2 (42.9% and 26.5% to 10.2% and 18.4%, respectively). Conversely, altered visuospatial, language, and orientation increased between T1 and T2 (16.3%, 36.7%, and 40.8%, respectively). Additionally, patients' global cognitive functioning at T1 was predicted by the language and executive domains in a subacute phase (p = 0.031 and p = 0.001, respectively), while in the long term, only attention (p = 0.043) and executive (p = 0.019) domains intervened. Overall, these results confirm the importance of a domain-specific approach to target cognitive recovery across time in stroke patients.

Effectiveness of dynamic neuromuscular stabilization, neurodevelopmental techniques and proprioceptive neuromuscular facilitation on trunk and gait parameters in patients with subacute stroke: A three-arm parallel randomised clinical trial

Background Today, stroke is the principal cause of demise in both developed and developing countries. There are different techniques used to treat patients with sub-acute stroke. Trunk muscles play a key role, i.e. in keeping the spine and trunk in place. This stabilization requires moving the head and extremities freely and selectively. The aim of this study is to compare the effectiveness of dynamic neuromuscular stabilization (DNS), neurodevelopmental techniques (NDT) and proprioceptive neuromuscular facilitation (PNF) on trunk and gait parameters in the subacute phase of stroke. This study is intended to ascertain the efficacy of all three approaches individually and to compare the effectiveness of DNS, NDT and PNF on trunk and gait parameters. Furthermore, the findings of this study could be used to assist post-stroke survivors in their early recovery and improve their level of independence. Methods In this interventional study, participants will be divided into three groups, and in each group, 20 patients will be assigned randomly to each group using the sequentially numbered opaque sealed envelope method. Group A patients will be given DNS, Group B will be given NDT, and Group C will be given PNF. The patients will be given treatment for five days for four consecutive weeks. Outcome measures that will be used are trunk impairment scale (TIS), dynamic gait index (DGI) and gait parameters. Data will be collected before and after the 4-week treatment period. Conclusions After the study, a conclusion will be drawn regarding which treatment technique is most suitable among all the three strategies for treating stroke patients if the hypothesis of the study is found valid. Clinical Trials Registry – India (CTRI) reference no. CTRI/2022/06/043037; date of registration 22/05/2022.