Non-traumatic Brain Injury Research Articles

Retrospective case-control study to compare exoskeleton-assisted walking with standard care in subacute non-traumatic brain injury patients.

Advanced technologies are increasingly used to address impaired mobility after neurological insults, with growing evidence of their benefits for various populations. However, certain robotic devices have not been extensively investigated in specific conditions, limiting knowledge about optimal application for healthcare. To compare effectiveness of conventional gait training with exoskeleton-assisted walking for non-traumatic brain injury during early stage rehabilitation. Clinical evaluation data at admission and discharge were obtained in a retrospective case-control design. Patients received standard of care physical therapy either using Ekso GT or not. Within- or between-group statistical tests were performed to determine change over time and interventional differences. This study analyzed forty-nine individuals (33% female), 20 controls and 29 Ekso participants who were equivalent at baseline. Both groups improved in Functional Independence Measure scores and ambulation ability (p < .00001 and p < .001, respectively). Control subjects demonstrated significantly different distance walked and assistance level values at discharge from those who were treated with the exoskeleton (p < .01). Robotic locomotion is non-inferior for subacute functional recovery after non-traumatic brain injury. Conventional therapy produced larger gait performance gains during hospitalization. Further research is needed to understand specific factors influencing efficacy and the long-term implications after rehabilitation.

Protective and therapeutic effects of okra seed in acute nontraumatic brain injury

Aim The purpose of this study was to examine the protective and therapeutic effects of okra (Abelmoschus esculentus [AE]) seed extract, with its known antioxidant, immunomodulatory, and anti-inflammatory properties, in an acetaminophen (paracetamol, N-acetyl- para-aminophenol)-induced model of hepatotoxicity and subsequent acute non-traumatic brain damage. Material and Method Forty male Wistar rats were randomly divided into five equal groups, control, paracetamol (P), okra seed extract (AE), okra seed extract + paracetamol (P + AE), and okra seed extract + paracetamol + N-acetyl cysteine (NAC) (P + AE + N). AE was administered by oral gavage through a gastric tube at 600 mg/kg/day for seven days. On the eighth day of the procedure, a single 1 g/kg dose of paracetamol and 300 mg/kg NAC were injected via the intraperitoneal route 1.5 h after AE administration. Rat tissue specimens were subsequently subjected to biochemical and histopathological analyses. Levels of markers such as S100 calcium-binding protein B (S100B), neuron-specific enolase (NSE), and matrix membrane metalloproteinase-9 (MMP-9) were investigated from rat serum specimens. Malondialdehyde (MDA) and superoxide dismutase (SOD) were also measured to determine oxidant-antioxidant status. Results S100B, NSE, MMP-9, MDA levels, and SOD enzyme activities were examined using biochemical methods. MDA levels were significantly lower in the P + AE group and MMP-9 levels in the AE, P + AE, and P + AE + N groups compared to the P group. Histopathological examination results supported the biochemical findings Conclusion Okra seed extract exhibits a protective and therapeutic effect against non-traumatic brain damage resulting from acute paracetamol intoxication. We think that this benefit of AE derives from its antioxidant property.

Multimodal Prediction of 3- and 12-Month Outcomes in ICU Patients with Acute Disorders of Consciousness

BackgroundIn intensive care unit (ICU) patients with coma and other disorders of consciousness (DoC), outcome prediction is key to decision-making regarding prognostication, neurorehabilitation, and management of family expectations. Current prediction algorithms are largely based on chronic DoC, whereas multimodal data from acute DoC are scarce. Therefore, the Consciousness in Neurocritical Care Cohort Study Using Electroencephalography and Functional Magnetic Resonance Imaging (i.e. CONNECT-ME; ClinicalTrials.gov identifier: NCT02644265) investigates ICU patients with acute DoC due to traumatic and nontraumatic brain injuries, using electroencephalography (EEG) (resting-state and passive paradigms), functional magnetic resonance imaging (fMRI) (resting-state) and systematic clinical examinations.MethodsWe previously presented results for a subset of patients (n = 87) concerning prediction of consciousness levels in the ICU. Now we report 3- and 12-month outcomes in an extended cohort (n = 123). Favorable outcome was defined as a modified Rankin Scale score ≤ 3, a cerebral performance category score ≤ 2, and a Glasgow Outcome Scale Extended score ≥ 4. EEG features included visual grading, automated spectral categorization, and support vector machine consciousness classifier. fMRI features included functional connectivity measures from six resting-state networks. Random forest and support vector machine were applied to EEG and fMRI features to predict outcomes. Here, random forest results are presented as areas under the curve (AUC) of receiver operating characteristic curves or accuracy. Cox proportional regression with in-hospital death as a competing risk was used to assess independent clinical predictors of time to favorable outcome.ResultsBetween April 2016 and July 2021, we enrolled 123 patients (mean age 51 years, 42% women). Of 82 (66%) ICU survivors, 3- and 12-month outcomes were available for 79 (96%) and 77 (94%), respectively. EEG features predicted both 3-month (AUC 0.79 [95% confidence interval (CI) 0.77–0.82]) and 12-month (AUC 0.74 [95% CI 0.71–0.77]) outcomes. fMRI features appeared to predict 3-month outcome (accuracy 0.69–0.78) both alone and when combined with some EEG features (accuracies 0.73–0.84) but not 12-month outcome (larger sample sizes needed). Independent clinical predictors of time to favorable outcome were younger age (hazard ratio [HR] 1.04 [95% CI 1.02–1.06]), traumatic brain injury (HR 1.94 [95% CI 1.04–3.61]), command-following abilities at admission (HR 2.70 [95% CI 1.40–5.23]), initial brain imaging without severe pathological findings (HR 2.42 [95% CI 1.12–5.22]), improving consciousness in the ICU (HR 5.76 [95% CI 2.41–15.51]), and favorable visual-graded EEG (HR 2.47 [95% CI 1.46–4.19]).ConclusionsOur results indicate that EEG and fMRI features and readily available clinical data predict short-term outcome of patients with acute DoC and that EEG also predicts 12-month outcome after ICU discharge.

Amantadine for NeuroenhaNcement in acutE patients Study - a protocol for a prospective pilot proof of concept phase IIb study in intensive and intermediate care unit patients (ANNES)

BackgroundPersisting coma is a common complication in (neuro)intensive care in neurological disease such as acute ischemic stroke, intracerebral hemorrhage or subarachnoid hemorrhage. Amantadine acts as a nicotinic receptor antagonist, dopamine receptor agonist and non-competitive N-Methyl-D-aspartate receptor antagonist. Amantadine is a long-known drug, originally approved for treatment of influenza A and Parkinson`s Disease. It has been proven effective in improving vigilance after traumatic brain injury. The underlying mechanisms remain largely unknown, albeit anti-glutamatergic and dopaminergic effects might be most relevant. With limited evidence of amantadine efficacy in non-traumatic pathologies, the aim of our study is to assess the effects of amantadine for neuroenhancement in non-traumatic neurointensive patients with persisting coma.MethodsAn investigator-initiated, monocenter, phase IIb proof of concept open-label pilot study will be carried out. Based on the Simon design, 43 adult (neuro)intensive care patients who meet the clinical criteria of persisting coma not otherwise explained and < 8 points on the Glasgow Coma Scale (GCS) will be recruited. Amantadine will be administered intravenously for five days at a dosage of 100 mg bid. The primary endpoint is an improvement of at least 3 points on the GCS. If participants present as non-responders (increase < 3 points or decrease on the GCS) within the first 48 h, the dosage will be doubled from day three to five. Secondary objectives aim to demonstrate that amantadine improves vigilance via alternative scales. Furthermore, the incidence of adverse events will be investigated and electroencephalography (EEG) will be recorded at baseline and end of treatment.DiscussionThe results of our study will help to systematically assess the clinical utility of amantadine for treatment of persisting coma in non-traumatic brain injury. We expect that, in the face of only moderate treatment risk, a relevant number of patients will benefit from amantadine medication by improved vigilance (GCS increase of at least 3 points) finally leading to a better rehabilitation potential and improved functional neurological outcome. Further, the EEG data will allow evaluation of brain network states in relation to vigilance and potentially outcome prediction in this study cohort.Trial RegistrationNCT05479032.

Ferroptosis and mitochondrial dysfunction in acute central nervous system injury.

Acute central nervous system injuries (ACNSI), encompassing traumatic brain injury (TBI), non-traumatic brain injury like stroke and encephalomeningitis, as well as spinal cord injuries, are linked to significant rates of disability and mortality globally. Nevertheless, effective and feasible treatment plans are still to be formulated. There are primary and secondary injuries occurred after ACNSI. Most ACNSIs exhibit comparable secondary injuries, which offer numerous potential therapeutic targets for enhancing clinical outcomes. Ferroptosis, a newly discovered form of cell death, is characterized as a lipid peroxidation process that is dependent on iron and oxidative conditions, which is also indispensable to mitochondria. Ferroptosis play a vital role in many neuropathological pathways, and ACNSIs may induce mitochondrial dysfunction, thereby indicating the essentiality of the mitochondrial connection to ferroptosis in ACNSIs. Nevertheless, there remains a lack of clarity regarding the involvement of mitochondria in the occurrence of ferroptosis as a secondary injuries of ACNSIs. In recent studies, anti-ferroptosis agents such as the ferroptosis inhibitor Ferrostain-1 and iron chelation therapy have shown potential in ameliorating the deleterious effects of ferroptosis in cases of traumatic ACNSI. The importance of this evidence is extremely significant in relation to the research and control of ACNSIs. Therefore, our review aims to provide researchers focusing on enhancing the therapeutic outcomes of ACNSIs with valuable insights by summarizing the physiopathological mechanisms of ACNSIs and exploring the correlation between ferroptosis, mitochondrial dysfunction, and ACNSIs.

Plasma ubiquitin C-terminal hydrolase-L1 (UCH-L1) level as a blood biomarker of neurological damage after allogeneic hematopoietic cell transplantation.

Several biofluid-based biomarkers for traumatic brain injury show promise for use in diagnosis and outcome prediction. In contrast, few studies have investigated biomarkers for non-traumatic brain injury. We focused on ubiquitin C-terminal hydrolase-L1 (UCH-L1), which has been proposed as a screening tool for traumatic brain injury, and investigated whether the plasma UCH-L1 level could also be a useful biomarker in patients with non-traumatic brain injury. We measured UCH-L1 in 25 patients who had experienced neurological complications after allogeneic hematopoietic cell transplantation (HCT) and 22 control patients without any complications or graft-versus-host disease. Although UCH-L1 levels before HCT did not differ significantly (P = 0.053), levels after HCT were higher in patients with neurological complications compared with the control group (P < 0.001). At a UCH-L1 cutoff value of 0.072ng/ml, sensitivity was 68.0% and specificity was 100%. The statistical power of UCH-L1 for neurological complications seemed to be higher than that of CT and comparable to that of MRI. Thus, increased levels of UCH-L1 might reflect the presence of neurological damage even in patients with non-traumatic brain injury. Further large cohort investigations are warranted.

Long-Term Vocational Outcome at 15 Years from Severe Traumatic and Non-Traumatic Brain Injury in Pediatric Age.

Recent studies suggest that acquired brain injury with impaired consciousness in infancy is related to more severe and persistent effects and may have a cumulative effect on ongoing development. In this work, we aim to describe vocational outcome in a group of patients at 15 years from a severe brain lesion they suffered in developmental age. This study included a total of 147 patients aged 1.5 to 14 years with acquired brain lesion. Clinical and functional details ("Glasgow Outcome Scale", "Functional Independent Measure" and Intelligence Quotient) were collected at the time of their first hospitalization and vocational outcome was determined after 15 years. 94 patients (63.9%) presented with traumatic brain injury, while 53 patients (36.1%) presented with a brain lesion of other origin. Traumatic patients had a higher probability of being partly or fully productive than non-traumatic ones: 75.5% of traumatic subjects were working-taking into account limitations due to the traumatic event-versus 62.3% of non-traumatic ones. A relationship between some clinical variables and the vocational outcome was found. Rehabilitation should adequately emphasize "vocational rehabilitation" because a significant proportion of people experiencing a disorder of consciousness in childhood may show good social integration in adult age.

Accuracy of bedside sonographic measurement of optic nerve sheath diameter for intracranial hypertension diagnosis in the emergency department

Ultrasound measurement of the optic nerve sheath diameter (US ONSD) has been proposed as a method to diagnose elevated intracranial pressure (EICP), but the optimal threshold is unclear. The aim of this study was to assess the accuracy of US ONSD, as compared to head computed tomography (CT), in detecting EICP of both traumatic and non-traumatic origin. We conducted a prospective, cross-sectional, multicenter study. Patients presenting to the emergency department with a suspect of traumatic or non-traumatic brain injury, referred for an urgent head CT, underwent US ONSD measurement. A US ONSD ≥5.5 mm was considered positive. Sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios were calculated for three ONSD cut-offs: 5.5 (primary outcome), 5.0, and 6.0 mm. A receiver operating characteristic (ROC) curve was also generated and the area under the ROC curve calculated. Ninetynine patients were enrolled. The CT was positive in 15% of cases and the US ONSD was positive in all of these, achieving a sensitivity of 100% [95% confidence interval (CI) 78; 100] and a negative predictive value of 100% (95% CI 79; 100). The CT was negative in 85% of cases, while the US ONSD was positive in 69% of these, achieving a specificity of 19% (95% CI 11; 29) and a positive predictive value of 18% (95% CI 11; 28). The US ONSD, with a 5.5 mm cut-off, might safely be used to rule out EICP in patients with traumatic and non-traumatic brain injury in the ED. In limited-resources contexts, a negative US ONSD could allow emergency physicians to rule out EICP in low-risk patients, deferring the head CT.

A longitudinal follow-up study of parent-reported family impact and quality of life in young patients with traumatic and non-traumatic brain injury

Purpose Brain injuries (traumatic-/nontraumatic, TBI/nTBI) in young patients may lead to problems e.g., decreased health-related quality of life (HRQoL), and causes family impact. Knowledge regarding the family impact and the relationship with patients’ HRQoL over time is scarce. This follow-up study describes family impact/HRQoL and their mutual relationship in young patients (5–24 years) after TBI/nTBI. Materials and methods Parents of patients that were referred to outpatient rehabilitation completed the PedsQL™Family-Impact-Module questionnaire to assess the family impact and the parent-reported PedsQL™Generic-core-set-4.0 to assess patients’ HRQoL (lower scores: more family impact/worse HRQoL). Questionnaires were completed at the time of referral to rehabilitation (baseline) and one/two years later (T1/T2). Linear-mixed models were used to examine family impact/HRQoL change scores, and repeated-measure correlations (r) to determine longitudinal relationships. Results Two-hundred-forty-six parents participated at baseline, 72 (at T2), median patient’s age at baseline was 14 years (IQR:11–16), and 181 (74%) had TBI. Mean (SD) PedsQL™Family-Impact-Module score at baseline was 71.7 (SD:16.4) and PedsQL™Generic-core-set-4.0: 61.4 (SD:17.0). Over time, PedsQL™Family-Impact-Module scores remained stable, while PedsQL™Generic-core-set-4.0 scores improved significantly(p < 0.05). A moderately strong longitudinal correlation was found between family impact&HRQoL (r = 0.51). Conclusions Family impact does not tend to decrease over time but remained a considerable problem, although patients’ HRQoL improved. Next to focusing on patients’ HRQoL, it remains important to consider family impact and offer family support throughout rehabilitation. IMPLICATIONS FOR REHABILITATION This longitudinal study found that in young patients with traumatic brain injury (TBI) or non-traumatic brain injury (nTBI) referred for rehabilitation there is a considerable impact on the family until two years after referral, whereas the patients’ health-related quality of life (HRQoL) improved significantly. Improvements in patients’ quality of life status may not automatically lead to a decrease of family impact. Rehabilitation clinicians should monitor the impact on the family over time and provide long-term family support with special attention to parental worrying when needed. Clinicians should be aware that, despite significant differences between the clinical characteristics of patients with TBI and nTBI, the courses of family impact are very similar.

Therapeutic review: The role of tranexamic acid in management of traumatic brain injury, nontraumatic intracranial hemorrhage, and aneurysmal subarachnoid hemorrhage.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. To summarize current literature evaluating tranexamic acid in the management of intracranial bleeding associated with traumatic and nontraumatic brain injuries and implications for clinical practice. Intracranial hemorrhage, regardless of etiology, is associated with high morbidity and mortality. Tranexamic acid is an antifibrinolytic with anti-inflammatory properties shown to reduce mortality in trauma patients with extracranial injuries. In traumatic brain injury, a large randomized trial found no difference in outcomes when tranexamic acid was compared to placebo; however, subgroup analyses suggested that it may reduce head injury-related mortality in the context of mild-to-moderate injury if treatment occurs within 1 hour of symptom onset. More recent out-of-hospital data have disputed these findings and even suggested harm in severely injured patients. In spontaneous, nontraumatic intracranial hemorrhage, treatment with tranexamic acid did not result in a difference in functional status; however, rates of hematoma expansion, even though modest, were significantly reduced. In aneurysmal subarachnoid hemorrhage, tranexamic acid may prevent rebleeding, but has not led to improved outcomes or reduced mortality, and there is concern for increased incidence of delayed cerebral ischemia. Overall, tranexamic acid has not been shown to result in increased risk of thromboembolic complications across these classes of brain injury. Despite its favorable safety profile overall, tranexamic acid does not seem to improve functional outcomes and cannot be routinely recommended. More data are needed to determine which head injury subpopulations are most likely to benefit from tranexamic acid and which patients are at increased risk for harm.

VCSF Danger-associated Molecular Patterns After Traumatic and Nontraumatic Acute Brain Injury: A Prospective Study.

Danger-associated molecular patterns (DAMPs) may be implicated in the pathophysiological pathways associated with an unfavorable outcome after acute brain injury (ABI). We collected samples of ventricular cerebrospinal fluid (vCSF) for 5 days in 50 consecutive patients at risk of intracranial hypertension after traumatic and nontraumatic ABI. Differences in vCSF protein expression over time were evaluated using linear models and selected for functional network analysis using the PANTHER and STRING databases. The primary exposure of interest was the type of brain injury (traumatic vs. nontraumatic), and the primary outcome was the vCSF expression of DAMPs. Secondary exposures of interest included the occurrence of intracranial pressure ≥20 or ≥ 30mmHg during the 5 days post-ABI, intensive care unit (ICU) mortality, and neurological outcome (assessed using the Glasgow Outcome Score) at 3 months post-ICU discharge. Secondary outcomes included associations of these exposures with the vCSF expression of DAMPs. A network of 6 DAMPs (DAMP_trauma; protein-protein interaction [PPI] P=0.04) was differentially expressed in patients with ABI of traumatic origin compared with those with nontraumatic ABI. ABI patients with intracranial pressure ≥30mmHg differentially expressed a set of 38 DAMPS (DAMP_ICP30; PPI P< 0.001). Proteins in DAMP_ICP30 are involved in cellular proteolysis, complement pathway activation, and post-translational modifications. There were no relationships between DAMP expression and ICU mortality or unfavorable versus favorable outcomes. Specific patterns of vCSF DAMP expression differentiated between traumatic and nontraumatic types of ABI and were associated with increased episodes of severe intracranial hypertension.

Effect of single and combined median nerve stimulation and repetitive transcranial magnetic stimulation in patients with prolonged disorders of consciousness: a prospective, randomized, single-blinded, controlled trial.

To investigate the efficacy of median nerve stimulation (MNS) combined with repetitive transcranial magnetic stimulation (rTMS), MNS alone, and rTMS alone in elevating the level of consciousness in patients with prolonged disorders of consciousness (pDOC). We enrolled 75 eligible inpatients suffering from pDOC as a result of traumatic or non-traumatic brain injury. Participants were randomly assigned to one of the following three treatment groups: (1) rTMS+sham-MNS; (2) MNS + sham-rTMS; or (3) MNS + rTMS. The rTMS protocol involved stimulation above the left dorsolateral prefrontal cortex at a 10 Hz frequency and 90% resting motor threshold. The MNS protocol involved the delivery of a 15-20 mA current at the median nerve point 2 cm from the wrist crease of the right distal forearm. The primary outcome was the change from baseline of the Coma Recovery Scale-Revised (CRS-R) score after treatment. Secondary outcomes included post-treatment changes from baseline of the Glasgow Coma Scale (GCS) score, awaken ratio, electroencephalography (EEG) scores, and the latency and amplitude of N20 on somatosensory evoked potentials. Before the intervention, there were no significant differences between groups in the CRS-R, GCS scores, age, duration of pDOC, clinical diagnosis, EEG scores, latency and amplitude of N20, sex, job, marital status, education level, or disease etiology. Within the three groups, the total CRS-R, GCS scores and amplitude of N20 on both side significantly increased and latency of N20 on poor side significantly decreased post-intervention. Significantly greater improvement in CRS-R, GCS total scores, amplitude of N20 on both side and latency of N20 on the poor side were observed in the MNS + TMS group compared to those of the groups receiving rTMS alone or MNS alone. The patients receiving TMS and MNS intervention showed a greater EEG activity improvement, and the EEG activity improved ratio significantly differ between groups, while there were no significant differences in the awakening ratios between the three groups. The combination of MNS + rTMS was more efficacious in improving the level of consciousness than MNS alone or rTMS alone in patients with pDOC.

Non-coding RNAs and Exosomal Non-coding RNAs in Traumatic Brain Injury: the Small Player with Big Actions.

Nowadays, there is an increasing concern regarding traumatic brain injury (TBI) worldwide since substantial morbidity is observed after it, and the long-term consequences that are not yet fully recognized. A number of cellular pathways related to the secondary injury in brain have been identified, including free radical production (owing to mitochondrial dysfunction), excitotoxicity (regulated by excitatory neurotransmitters), apoptosis, and neuroinflammatory responses (as a result of activation of the immune system and central nervous system). In this context, non-coding RNAs (ncRNAs) maintain a fundamental contribution to post-transcriptional regulation. It has been shown that mammalian brains express high levels of ncRNAs that are involved in several brain physiological processes. Furthermore, altered levels of ncRNA expression have been found in those with traumatic as well non-traumatic brain injuries. The current review highlights the primary molecular mechanisms participated in TBI that describes the latest and novel results about changes and role of ncRNAs in TBI in both clinical and experimental research.

Characteristics and Outcomes of Medicare Patients Treated in Inpatient Rehabilitation Facilities: 2013-2018.

The aim of this study was to describe the characteristics and outcomes of Medicare patients treated in inpatient rehabilitation facilities (IRFs) in 2013 through 2018. A descriptive study was conducted. A total of 2,907,046 IRF Medicare fee-for-service and Medicare Advantage patient stays that ended in 2013 through 2018 were analyzed. The number of Medicare patients treated in IRFs increased by about 9%, from 466,092 in 2013 to 509,475 in 2018. Although IRF patients' age and racial/ethnic composition remained similar across the years, there was a shift in patients' primary rehabilitation diagnosis, with more patients with stroke, neurological conditions, traumatic and nontraumatic brain injury, fewer patients with orthopedic conditions, and fewer coded as having medically complex conditions. Across the years, the percentage of patients discharged to the community was between 73.0% and 74.4%. Rehabilitation nurses should have training and expertise in the management of patients with stroke and neurological conditions to provide high-quality IRF care. Between 2013 and 2018, the number of Medicare patients treated in IRFs increased overall. There were more patients with stroke and neurological conditions and fewer patients with orthopedic conditions. Changes to IRF and other post-acute care policies, Medicaid expansion, and alternative payment programs may partially be driving these changes.

Effects of comorbidity on post-acute outcomes in acquired brain injury: ABI-RESTaRT 1991-2020.

Current understanding of comorbidities associated with acquired brain injury (ABI) and the effects on post-acute ABI outcomes is poor. To describe the prevalence, severity and patterns of comorbidity for the pre-injury, acute and post-acute phases, and to examine the effects of post-acute comorbidities on functional independence and length of stay (LOS) at discharge from post-acute care. Retrospective whole-population cohort study of n=1,011 individuals with traumatic (TBI) or non-traumatic brain injury (NTBI), or eligible neurologic conditions admitted to a post-acute neurorehabilitation and disability support service in Western Australia (WA) between 1991 and 2020. Comorbidities were ascertained from internal electronic medical records and linked hospital and emergency department data from the WA Data Linkage System. We measured comorbidities across 14 body systems using the Cumulative Illness Rating Scale (CIRS) and Elixhauser Comorbidity Index (ECI), and functional independence with the UK Functional Independence Measure and Functional Assessment Measure (UK FIM+FAM). We used multilevel mixed-effect regression models to determine the effects of comorbidity on post-acute outcomes. NTBI was the most common diagnosis (54%), followed by TBI (34%) and neurologic conditions (10%). Pre-injury comorbidities were present in over half the cohort. Comorbidity prevalence increased significantly from 57% to 84% (∆+27%) and severity (mean ECI score) increased significantly from 2.1 to 13.8 (∆+11.7) between pre-injury and the acute phase and remained elevated at admission to post-acute services (82%, mean ECI score 7.3). Psychiatric comorbidity was the most prevalent (56%) and was associated with significantly poorer functional outcomes at discharge and an increase in LOS of 6.5 months. Genitourinary, musculoskeletal, eye, ear nose and throat, and renal comorbidities also had significant effects on post-acute outcomes. ABI has a long-term impact on multiple body systems. Identification and management of comorbidities is critical to maximize functional outcomes and reduce the cost of post-acute care.

Correlation between Glasgow Coma Scale with central venous pressure and near-infrared spectroscopy in patients with acquired brain injury in the intensive care unit of Adam Malik Hospital Medan

Abstract Background Acquired brain injury (ABI) is caused by trauma or nontrauma to the brain after birth. Increased intracranial pressure in patients with traumatic or nontraumatic brain injury affects the cerebral perfusion pressure. After traumatic brain injury, there is an increase in air content in the brain and an increase in volume of blood flow to the brain, which can cause increased intracranial pressure, herniation of brain tissue, impaired cerebral perfusion, and brain damage. Most patients with traumatic brain injury die from uncontrolled increases in intracranial pressure. Near-infrared spectroscopy (NIRS) and central venous pressure (CVP) monitoring are also associated with cerebral perfusion. This study aimed to determine the relationship between the Glasgow Coma Scale (GCS) scores and CVP and NIRS values in patients with ABI. Methods This prospective analytical study used a cross-sectional design to compare GCS scores with CVP and NIRS values in patients with traumatic and nontraumatic brain injury in the intensive care unit (ICU) of Haji Adam Malik Hospital Medan. GCS, CVP, and NIRS descriptive data in patients with brain injury were presented in terms of mean and standard deviation if the data were normally distributed, or median (interquartile range) values if the data were not normally distributed. The relationship between GCS scores and CVP and NIRS values was assessed using the Pearson correlation test if the data were normally distributed, or the Spearman test if the data were not normally distributed. Results In this study, the mean GCS score and CVP values were 7.04 ± 2.69 and 5.63 ± 25.82 mmHg, respectively. The right tissue oxygen saturation (StO2) was 55.61% ± 18.72%, and the left StO2 was 57.57% ± 17.48% with normally distributed data. There was no correlation between GCS scores and CVP values (P = 0.829), and no correlation between moderate GCS scores and right and left StO2 (P = 0.343; P = 0.121); however, there was a significantly strong positive correlation between severe GCS scores and right and left StO2 (P = 0.028, r = 0.656; P = 0.005, r = 0.777). Conclusion There was no significant correlation between GCS scores and CVP values, and no correlation between moderate GCS scores and NIRS values; however, there was a significantly strong positive correlation between severe GCS scores and NIRS values in patients with ABI at the ICU of Haji Adam Malik Hospital Medan.

Clinical characteristics and prognosis of paroxysmal sympathetic hyperactivity in patients with severe nontraumatic brain injury

ABSTRACT Objective This prospective study investigated and analyzed the clinical characteristics and prognosis of paroxysmal sympathetic hyperactivity (PSH) in patients with severe nontraumatic brain injury. Methods Patients presenting with severe nontraumatic brain injury with PSH from July 2018 to June 2019 were enrolled. A PSH assessment measure ≥ 8 points was used as the criterion for PSH. Clinical data, indicators related to PSH, treatment effects and the prognosis were prospectively collected and analyzed. Results A total of 220 patients with severe nontraumatic brain injury were analyzed, and PSH occurred in 8 patients (3.6%). The primary neurological diseases included acute cerebral infarction, anti-N-methyl-D-aspartate receptor encephalitis, hypoxic encephalopathy and acute disseminated encephalitis. The Glasgow Coma Scale score was lower than 8 in the 8 patients with PSH. Seven of these eight patients had a Glasgow outcome scale (GOS) score of 3 or less than 3, and one patient had a GOS of 5 after 6 months. The medicines that effectively controlled PSH included dexmedetomidine, clonazepam, midazolam and diazepam. Conclusions Although the incidence was lower for nontraumatic brain injury complicated with PSH than for traumatic brain injury, patients with PSH had a more severe disease state and poorer prognoses. Dexmedetomidine might effectively control PSH.

High-fat diet feeding triggers a regenerative response in the adult zebrafish brain.

Non-alcoholic fatty liver disease (NAFLD) includes a range of liver conditions ranging from excess fat accumulation to liver failure. NAFLD is strongly associated with high-fat diet (HFD) consumption that constitutes a metabolic risk factor. While HFD has been elucidated concerning its several systemic effects, there is little information about its influence on the brain at the molecular level. Here, by using a high-fat diet (HFD)-feeding of adult zebrafish, we first reveal that excess fat uptake results in weight gain and fatty liver. Prolonged exposure to HFD induces a significant increase in the expression of pro-inflammation, apoptosis, and proliferation markers in the liver and brain tissues. Immunofluorescence analyses of the brain tissues disclose stimulation of apoptosis and widespread activation of glial cell response. Moreover, glial activation is accompanied by an initial decrease in the number of neurons and their subsequent replacement in the olfactory bulb and the telencephalon. Long-term consumption of HFD causes activation of Wnt/β-catenin signaling in the brain tissues. Finally, fish fed an HFD induces anxiety, and aggressiveness and increases locomotor activity. Thus, HFD feeding leads to a non-traumatic brain injury and stimulates a regenerative response. The activation mechanisms of a regeneration response in the brain can be exploited to fight obesity and recover from non-traumatic injuries.

Predictors of caregiver burden in caregivers of individuals with traumatic or non-traumatic brain injury: A scoping review.

Caregivers of individuals with traumatic (TBI) or non-traumatic (nTBI) brain injuries are at risk of significant caregiver burden. Consequently, it is crucial to examine predictors of caregiver burden to enable early identification and intervention. To examine predictors of caregiver burden in caregivers of individuals with TBI/nTBI. A scoping review was conducted in the bibliographic databases PubMed, EMBASE (Ovid) and APA PsycInfo (EBSCO). Search terms included: 'acquired brain injur*', 'traumatic brain injur*', 'brain injur*', 'non-traumatic brain injur*', or 'stroke*' combined with 'burden', 'caregiver burden', 'perceived burden', or 'caregiver strain'. The search was limited to articles written in English and published in academic journals between 2000 and March 2022. EndNote was used to manage the references and identify duplicates. Twenty-four studies were included. Care recipient-related predictors of caregiver burden included more severe injuries, functional disabilities (including decreased physical and neuropsychological functioning), and worse mental health. Caregiver-related predictors included more time spent caregiving, worse mental health, and unmet needs. For several predictor variables, evidence was mixed or vague. The results highlight which caregivers are at risk of caregiver burden and point to several areas of potential intervention to prevent caregiver burden. Future research should explore the relationship between characteristics of the caregiver and caregiver burden, including coping style, problem-solving techniques, and personality, as these have been sparsely investigated and are potentially modifiable through intervention. Further research is needed to elucidate if burden can be prevented by interventions targeting caregivers at risk. Addressing these gaps may clarify the link between caregiver burden and predictor variables and assist in development of interventions that may prevent burden.

Neuro-Optometric Treatment of Wall-eyed Bilateral Internuclear Ophthalmoplegia (WEBINO)

Background Wall-eyed Bilateral Internuclear Ophthalmoplegia (WEBINO) is an ocular motility disorder characterized by bilateral exotropia in primary gaze, bilateral internuclear ophthalmoplegia with defective adduction of both eyes and nystagmus of the contralateral eye on abduction. Convergence is impaired because the lesion is in the midbrain. The etiology of WEBINO includes demyelination, stroke, and tumors, but midbrain infarction is the most common.1 Although extraocular muscle surgery and botulinum toxin injections are typically used for management2 of WEBINO, neuro-optometric rehabilitation can be utilized as an effective option to improve vision. Case Report A 39-year-old Caucasian male with non-traumatic brain injury due to left intraparenchymal hemorrhage from stroke, presented with WEBINO and multiple vision signs and symptoms, including blurred vision, alternating exotropia, diplopia, and strabismus. During the previous 8 months, he participated in physical therapy, occupational therapy, and speech therapy. He had difficulty participating in his therapies due to his vision issues. Single vision distance lenses were prescribed to improve vision clarity and 6 in-office neuro-optometric rehabilitation sessions were administered to improve range of motion of eye movements and to improve vision. Conclusions Neuro-optometric rehabilitation utilizes a systematic approach to treating patients with binocular vision dysfunction, while integrating cognitive, motor, and sensory skills. Prognosis is optimized with an individualized approach. Top-down processing stimulates the brain in a more direct way to elicit plasticity-mediated motor relearning.3 In this case, extraocular muscle surgery and botulinum toxin injections were not optimal choices and neuro- optometric rehabilitation was utilized to manage WEBINO and improve quality of life.