Search Results (247)

Traumatic brain injury (TBI) is one of the leading causes of acquired epilepsy, with a significant proportion of patients developing post-traumatic epilepsy (PTE) even months or years after the initial injury. The identification of reliable imaging biomarkers able to predict epileptogenesis remains a major clinical challenge. In recent years, diffusion-weighted imaging (DWI) and structural connectome analysis have emerged as promising tools to investigate brain network alterations associated with late seizure development. Machine learning approaches may further support the detection of predictive patterns in complex neuroimaging data. The goal of this study is to perform a binary classification between seizure-free and late seizure-affected patients following TBI, with a specific focus on the identification of the anatomical regions potentially connected with late seizure development. A dataset of 59 diffusion weighted images (DWI) scans from the EpiBioS4Rx project, including 42 seizure-free and 17 late seizure-affected TBI patients, was analyzed. A Random Forest classification algorithm was applied, incorporating network feature importance based on the Gini index to investigate model’s decisions and allow a clinical interpretation. The model reported a 69% ± 0.03 accuracy for discrimination and a 73% AUC ± 0.05. Despite the limited and imbalanced nature of the dataset, and the fact that the performance does not significantly exceed chance once all data-dependent steps are taken into account, our approach allows us to achieve accurate classification results compared to the literature and to identify brain regions potentially associated with epileptogenesis. Full article

Modern societies are becoming increasingly dependent on electronics, leading to an increase in visual symptoms. Vergence endurance, the ability to sustain performance, may serve as a quantitative metric to complement symptom surveys to assess vergence performance during near visual tasks. To quantify vergence endurance, 48 participants, aged 15 to 23 years with normal binocular vision, completed a 15 min symmetrical disparity vergence step task to assess potential changes in peak vergence speed over the course of the experiment. Peak velocity, final amplitude, and the slope of the linear regression fit of the peak velocity as a function of stimulus recording were quantified for convergence and divergence responses using an eye tracker integrated in a virtual reality headset. Peak velocity was sustained by 63% and 69% of participants for convergence and divergence eye movements, respectively. Convergence and divergence responses were significantly different for peak velocity (p < 0.001) and vergence endurance (p < 0.03). The endurance metric tool has potential that may help shape future clinical applications for those with acquired brain injuries, including concussions or neurodegenerative diseases such as multiple sclerosis or Parkinson’s disease. Full article

Background/Objectives: The emergence of SARS-CoV-2 variants and breakthrough infections underscores the need for next-generation vaccines capable of protecting from natural infection and/or preventing virus transmission. Intranasal vaccination offers a promising approach by eliciting local immune responses in the nasal mucosa, the primary site of infection and reservoir for transmissible virus. We evaluated two live-attenuated, respiratory syncytial virus-vectored vaccines in which the RSV F and G surface glycoproteins were replaced with a chimeric SARS-CoV-2 Spike protein from the ancestral USA/WA-1/2020 strain (MV-014-212) or the Delta variant (MV-014-212-delta). Methods: K18-hACE2 mice and LVG Syrian hamsters were vaccinated with a single intranasal dose of MV-014-212 or MV-014-212-delta. Systemic and mucosal immunity were assessed following vaccination, and protection was evaluated following Delta SARS-CoV-2 challenge. In vaccinated hamsters, morbidity, viral shedding, and lung inflammation and injury were also assessed following natural exposure to infected cagemates. Results: A single intranasal dose of either vaccine elicited systemic and mucosal immunity in K18-hACE2 mice, including serum neutralizing antibodies, Spike-specific memory B cells and plasmablasts, and Spike-specific CD8⁺ lung-resident memory T cells. Although MV-014-212-delta vaccination provided the best protection against the Delta variant virus challenge, both vaccines decreased viral loads in nasal discharge, lung, and brain, and reduced weight loss and mortality. In naturally acquired infection studies, vaccinated hamsters exposed to infected cagemates exhibited minimal weight loss, limited viral replication within the nasal mucosa, and attenuated lung pathology. Conclusions: Intranasal RSV-vectored vaccines can elicit broad protective respiratory immunity, suggesting that this platform could be leveraged for other respiratory pathogens. Full article

Background: Spasticity significantly impairs functional recovery after severe acquired brain injury. Current management methods predominantly rely on pharmacological interventions, which can cause substantial side effects or require invasive medical procedures in refractory cases. Focal muscle vibration, a noninvasive technique that applies mechanical vibrations to muscle–tendon units and alters spinal and cortical excitability via proprioceptive pathways, has been effective in reducing spasticity in subjects with stroke. However, there is limited data to support focal muscle vibration as a viable option for improving functional recovery in patients with severe acquired brain injury. Objectives: To evaluate the clinical effects of adding focal muscle vibration to standard physiotherapy compared with standard physiotherapy alone in patients with severe acquired brain injury and spastic hypertonia. Methods: Twenty-four patients were randomly assigned to receive focal muscle vibration in addition to standard care (n = 12) or standard care alone (n = 12) for 3 weeks. Assessments were conducted at baseline, immediately after physiotherapy, and 3 weeks after physiotherapy. The outcomes assessed included the Modified Ashworth Scale, Disability Rating Scale, Modified Barthel Index, and three pain measures. Results: A significant reduction in spasticity was observed in the focal muscle vibration group, as indicated by the Modified Ashworth Scale scores (p = 0.014). Disability Rating Scale scores demonstrated a statistically significant decrease in disability ratings at the end of treatment (p = 0.002) and during the follow-up phase (p = 0.002). Between-group comparisons of change scores revealed a statistically significant improvement in disability ratings in the focal muscle vibration group during the treatment phase (p = 0.011). Significant functional gains were noted on the Disability Rating Scale, which persisted at the follow-up evaluation. Conclusions: Focal muscle vibration reduces muscle spasticity and improves functional status in patients with severe acquired brain injury during inpatient rehabilitation. Future studies with larger sample sizes, blinded assessments, and stratified randomization are needed to verify these findings and develop standardized treatment protocols for this underserved population. Full article

Patients following brain tumour resection experience significant disability, yet rehabilitation is not typically delivered prior to adjuvant treatment such as radiation or chemotherapy. This study aims to characterize the medical and functional profiles, and function outcomes of patients with brain tumour admitted over the past four years to a pilot inpatient prehabilitation programme following brain tumour resection but prior to adjuvant therapy, and to compare these findings with those of patients in a standard acquired brain injury rehabilitation programme. We retrospectively reviewed the charts from a randomly selected sample of 58 prehabilitation inpatients and 112 patients with acquired brain injuries at Toronto Rehabilitation Institute between March 2020 and December 2024. Data abstracted included demographics, medical and functional profiles, Functional Independence Measure (FIM) scores, and discharge parameters. Compared with acquired brain injury subjects, prehabilitation subjects had significantly less physical (47% vs. 86%, p < 0.0001) but more communication (46% vs. 20%, p = 0.0005) impairments, though with similar mean FIM change (22.5 vs. 26.0, p = 0.082) and FIM efficiency (1.1 vs. 1.0, p = 0.78). While not reaching significance, they also experienced more mood issues during rehabilitation (30% vs. 18%, p = 0.075). These findings support that prehabilitation after brain tumour surgery but before adjuvant therapy is clinically effective within existing ABI rehabilitation programmes. However, prehabilitation programmes may benefit from staffing models that emphasize communication supports and mental health expertise. Full article

Background: Traumatic brain injury (TBI) and hypoxic-ischemic encephalopathy (HIE) cause significant pediatric morbidity through primary insults and secondary cascades like excitotoxicity, neuroinflammation, and impaired plasticity. Nerve growth factor (NGF) promotes neuroprotection, anti-inflammation, and repair, but delivery challenges persist. This review evaluates preclinical and clinical evidence on intranasal human recombinant NGF (hr-NGF) to enhance neurorepair in pediatric TBI and HIE patients. It aims to clarify the potential of intranasal hr-NGF as part of future multimodal approaches to enhance brain repair and improve functional recovery across the lifespan. Methods: A PRISMA-guided literature search (2000–2025) was conducted across Scopus, PubMed, and Cochrane CENTRAL using terms like “intranasal NGF”, “TBI”, “HIE”, and “pediatric”. Eligible studies involved pediatric brain injury patients receiving NGF, with outcomes via clinical scales, imaging, or EEG. Results: Preclinical models showed that intranasal NGF reduces lesion volume, inflammation, and deficits while boosting angiogenesis and cholinergic function. Clinically, one child with meningitis and five TBI cases exhibited improved consciousness, spasticity, motor scores, cognition, and brain imaging. Three HIE cases gained voluntary movements, expressivity, and perfusion. No adverse events occurred related to hr-NGF administration. Conclusions: Intranasal hr-NGF safely reactivates plasticity in pediatric brain injury, yielding motor, cognitive, and neurophysiological gains. Preliminary data support multimodal use, but randomized trials are needed to optimize protocols and confirm efficacy. Full article

Background/Objectives: After an acquired brain injury (ABI), caregiver burden in family members is a clinical concern. Prior research has demonstrated that improved self-awareness in survivors of an ABI reduces caregiver burden. We examined the relationship between caregiver burden and ABI survivors’ levels of self-awareness across a span of injury chronicity following discharge from outpatient holistic milieu neurorehabilitation. Method: This retrospective observational study analyzed data on 59 individuals with heterogeneous ABIs who participated in an outpatient holistic milieu neurorehabilitation program from 2021 to 2025. This study utilized the discrepancy model of the Mayo-Portland Adaptability Inventory-4 (MPAI-4) to measure self-awareness in survivors of an ABI by calculating a discrepancy score from the self- and caregiver-rated MPAI-4 total score. Demographic information (age, education, race/ethnicity), injury history (injury type, age at injury, chronicity), program variables (length of program participation), functionality (MPAI-4), and caregiver burden (Zarit Burden Interview) at discharge were collected. Results: In order to predict caregiver burden based on self-awareness of an ABI survivor and time since injury, a multiple linear regression analysis was used. Although the multiple regression model significantly predicted caregiver burden, only self-awareness added significantly to the prediction and accounted for a modest proportion of the variance in caregiver burden. Conclusions: Self-awareness, as measured by utilizing the MPAI-4 discrepancy model, explained a modest proportion of the variance in caregiver burden regardless of time since injury. Among family members of survivors of an ABI, self-awareness of the survivor is a predictor of burden experienced by the family and would be beneficial to address as part of neurorehabilitation. Full article

Background/Objectives: Severe acquired brain injury (sABI) disrupts early rehabilitation because arousal fluctuates, trunk control is fragile, and agitation limits therapy tolerance; land-based practice is frequently constrained by fall risk and staffing. We aim to reframe aquatic therapy as a programmable multisensory environment to stabilize arousal and support axial alignment before conventional impairment targets are feasible. Here, programmable denotes the deliberate titration and reporting of water depth, turbulence or perturbation, temperature, body orientation, and flotation and manual support as intervention inputs. Methods: This perspective integrates principles from neurobehavioral assessment, motor control, and immersion physiology to propose the Arousal–Alignment–Action loop as a falsifiable model and to define manipulable aquatic inputs (water depth, turbulence or perturbation, temperature, body orientation, and flotation and manual support) as dosing parameters. We outline a pragmatic testing ladder (within-session micro-experiments, feasibility studies, and embedded evaluations) and a minimal outcomes and confounder set to support cumulative evidence. Results: The framework links state regulation to alignment and goal-directed behavior, specifies predictions that can fail, and highlights boundary conditions (sedation, autonomic instability, pain, recent surgery or wounds, and cervical or cardiopulmonary constraints). A minimal outcome package spanning arousal/responsiveness, trunk control, behavioral dysregulation, participation/tolerance, and basic physiology is proposed, with optional objective adjuncts for mechanism-oriented studies. Conclusions: Treating water as a measurable and titratable medium, rather than a generic modality, may reduce early intensity bottlenecks and improve implementability and comparability of aquatic neurorehabilitation research in medically stable sABI; however, the model is intended as hypothesis-generating until supported by stronger direct clinical evidence. Full article

Background/Objectives: Traumatic brain injury (TBI) affects more than 50 million people annually worldwide. Challenges in managing moderate-to-severe TBI include high rates of hospital-acquired infections and substantial variability in discharge disposition, and these combined challenges contribute significantly to the cost and trajectory of health recovery. Although current strategies such as antibiotic-impregnated external ventricular drains (EVDs) offer some benefit in controlling infections, they remain limited by high cost and inconsistent implementation. A clearer understanding of clinical and demographic factors associated with infection risk and discharge disposition are essential for improving care pathways. This study aims to identify and quantify key determinants of infection and discharge outcomes in patients with TBI. Methods: The National Trauma Database (NTDB) was queried using structured query language (SQL) based on predefined inclusion criteria (adult patients with ICD-coded TBI), input variables (basic demographics, injury location and severity, and vital signs), and specified outcome variables (emergency department discharge disposition, infection, and sepsis) to identify and filter the eligible patient cohort. A set of machine learning models were trained for each outcome (e.g., Emergency Department (ED) discharge, types of infections, and sepsis). Results: Data from 310,494 patients were extracted. The prediction model we developed, the Predictive TBI-Disposition Model (PTDM), was able to predict the outcome of a patient’s discharge with 96% accuracy. The accuracy of the models for infection and sepsis was 93% and 94%, respectively. Conclusions: Demographic and clinical factors significantly influence the discharge disposition and infection risk among TBI patients. Machine learning models demonstrated strong predictive performance, suggesting their utility in early risk stratification and targeted clinical decision-making. Full article

Shoulder spasticity is a common consequence of upper motor neuron lesions and may be associated with soft tissue contractures, limiting functional recovery. While both cryoneurolysis and tendon lengthening procedures are used individually in refractory cases, their combined effect has not been clearly established. It is consequently necessary to assess the efficacy of combining cryoneurolysis and percutaneous pectoral tenotomy in reducing shoulder spasticity and improving passive range of motion in patients with refractory shoulder spasticity and contracture. This retrospective, single-centre cohort study included 15 adults (≥19 years) with chronic shoulder spasticity and clinically confirmed musculotendinous contracture, previously treated with botulinum toxin injections without sufficient functional response, and free of pharmacological effects (last injection >4 months prior). All patients underwent cryoneurolysis targeting motor branches to the pectoral muscles. Outcomes included Modified Ashworth Scale (MAS) and shoulder Passive Range Of Motion (PROM). The combined approach provided significant improvements in spasticity severity for shoulder flexion (p < 0.01) and abduction (p < 0.01), and significant improvements in maximum PROM for shoulder flexion (p < 0.0001) and abduction (p < 0.0001). Combining cryoneurolysis and pectoral tenotomy appears feasible, safe, and clinically beneficial in selected patients with both spasticity and tendon contracture. Cryoneurolysis addresses the neural component, while tenotomy may restore mechanical excursion. This sequential diagnostic and therapeutic approach may enhance personalized management of mixed spastic–contracture shoulder limitations and could be applicable to other joints. Full article

Monitoring intracranial pressure (ICP) dynamics is critical for the management of traumatic brain injury, stroke, other neurosurgical conditions, and cerebral blood flow autoregulation; however, invasive ICP monitoring carries risks such as infection, hemorrhage, and sensor zero drift. Increasing evidence suggests that ICP waveform morphology provides clinically relevant information beyond mean ICP value alone. In this first-in-human prospective comparative clinical study, we evaluated the feasibility and accuracy of a novel, fully passive, non-invasive ICP pulse waveform monitoring system (Archimedes 02) based on the detection of eyeball mechanical movement. Fifteen intensive care unit patients (6 males, 9 females; mean age 57.1 ± 18.8 years) with clinically indicated invasive ICP monitoring or external ventricular drainage were enrolled. Three-minute monitoring sessions were performed to simultaneously acquire non-invasive ICP pulse waveforms, invasive ICP waveforms, and invasive radial artery blood pressure (ABP) waveforms. Averaged waveforms were derived for each patient and compared graphically and using correlation analysis. Non-invasive ICP pulse waves recorded with Archimedes 02 showed a strong correlation with invasive ICP waveforms ($\overline{\mathrm{R}}$ = 0.965). In contrast, correlations between non-invasive ICP and ABP waveforms ($\overline{\mathrm{R}}$ = 0.699), as well as between invasive ICP and ABP waveforms ($\overline{\mathrm{R}}$ = 0.749), were lower. These findings indicate that the non-invasive signal primarily reflects ICP dynamics rather than arterial blood pressure. This novel non-invasive ICP monitoring approach has the potential to enhance neurocritical care, particularly in settings where invasive monitoring is impractical or unavailable. Further validation in larger and more diverse patient populations is warranted. Full article

Objectives: Dysphagia is a major complication of acquired brain injury (ABI) in children; however, its trajectory and prognostic indicators remain insufficiently characterized. This study aimed to identify predictors of dysphagia and its recovery following pediatric ABI. Methods: This retrospective study included all children admitted with ABI to tertiary pediatric rehabilitation center between 2014 and 2017. Data were collected from electronic medical records. Results: One hundred children aged 2:00–17:11 years were included; 61% had dysphagia at admission. Participants with dysphagia received speech–language pathology (SLP) treatment, with a recovery rate of 78.68%. Treatment duration was significantly shorter among children who recovered (36 days) compared with those who did not (136 days; p < 0.001). Dysphagia at admission was associated with mechanical ventilation, duration of unconsciousness, duration of acute hospitalization, CNS tumor etiology, cranial nerve impairment (V, IX, X, XII), voice and speech impairments, and cognitive and behavioral impairments. Logistic regression showed that reduced consciousness, cranial nerve impairment, voice disorders, and CNS tumors explained 70.6% of dysphagia likelihood. Non-recovery was associated with unconsciousness, enteral feeding, hypoglossal injury, and dysphagia severity at admission. Level of consciousness at admission explained 33.7% of recovery likelihood. Conclusions: Dysphagia was highly prevalent among children with ABI. Recovery rates following SLP treatment were high and were associated with level of consciousness at admission to rehabilitation. Full article

Background: Acquired brain injury (ABI) often disrupts binocular vision, causing deviations on the cover test and reduced stereopsis that impair functional visual performance. This study investigated the effects of a dichoptic vision therapy protocol—based on an immersive virtual reality (VR) system—on visual field parameters, oculomotor reaction times, and self-reported visual symptoms in adults with ABI. Methods: In a controlled parallel-group design, adult ABI patients (median age 51 years) were assigned to an experimental group (dichoptic VR therapy) or a control group. Six sessions of visual therapy were performed. Primary outcomes included perimetric visual field indices and oculomotor reaction times; the secondary outcome was the Brain Injury Vision Symptom Survey (BIVSS) score. Etiology (stroke vs. traumatic brain injury) was recorded. Results: No statistically significant improvements were found in perimetric visual field indices (p > 0.05), except for a slight gain in the top-right quadrant in the experimental group. Reaction times did not differ significantly between groups. However, the experimental group reported a greater reduction in visual symptoms as measured by the BIVSS. Patients with traumatic brain injury exhibited better functional improvement, particularly in the top-left quadrant (p = 0.04). Conclusions: Dichoptic VR-based therapy did not restore perimetric field losses in ABI patients but reduced visual symptoms and may enhance functional adaptation of residual vision rather than structural recovery. The therapeutic response varied by etiology, favoring traumatic brain injury. Larger, longer trials integrating objective and subjective measures, including neuroimaging, are warranted. Full article

Background: Acquired brain injury (ABI) affects manual dexterity (MD) and cognitive functions, limiting daily activity performance. Occupational therapy aims to improve functionality and quality of life. Objective: To examine and describe the available evidence on the impact of MD training on cognitive processes and functional performance in adults with stroke, as well as to identify the most commonly used assessment tools and intervention techniques. Methods: Scoping review. A systematic literature search was conducted in PubMed and Scopus to identify experimental studies from the last 10 years involving adults with ABI who participated in interventions targeting upper-limb, MD, and cognitive function. A three-phase screening was carried out by two authors with duplicates removed using Zotero version 7.0. Results: Ten articles published between 2016 and 2023 were included. The most frequent interventions involved robotics and virtual reality. Eight studies were conducted by occupational therapists or included occupational therapy involvement, while two were conducted by physiotherapists. Training MD and upper-limb motor skills led to improvements in attention, memory, and executive functions. Conclusions: Findings support combined motor–cognitive interventions carried out by occupational therapists or physiotherapists to optimize rehabilitation outcomes, although further research is needed to strengthen the evidence. Full article

Background/Objectives: Mitochondrial dysfunction is a major cause of brain injury in patients with primary mitochondrial disease. New mitochondrial therapeutics and non-invasive tools for efficacy monitoring are urgently needed. To these ends, succinate prodrug NV354 (methyl 3-[(2-acetylaminoethylthio)carbonyl]propionate) and diffuse optical techniques are promising. In this proof-of-concept study, we characterize NV354’s effects on microdialysis metrics of cerebral metabolism in a swine model of mitochondrial dysfunction and assess the associations of diffuse optical metrics with mitochondrial dysfunction and metabolic improvement. Methods: One-month-old swine received a four-hour co-infusion of rotenone with either the succinate prodrug NV354 (n = 5) or placebo (n = 5). Rotenone is a mitochondrial complex I inhibitor. Before and during co-infusion, cerebral metabolism was probed with microdialysis and diffuse optics. Microdialysis acquired interstitial lactate and pyruvate levels invasively, while diffuse optics measured changes in oxygen extraction fraction (OEF) and oxidized cytochrome-c-oxidase concentration (oxCCO). Results: Interstitial lactate continually increased in the placebo group (p < 0.01), but lactate levels plateaued in the NV354 group (p = 0.90). oxCCO also increased in the placebo group (p = 0.05), but OEF remained constant (p = 0.80). In the NV354 group, oxCCO increased (p < 0.01) while OEF decreased (p < 0.01). Conclusions: Microdialysis results suggest that NV354 treatment can increase oxygen metabolism in large animals with mitochondrial dysfunction. The optical oxCCO metric was also sensitive to metabolic changes induced by rotenone and NV354 administration. Full article