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Introduction: Diffusion Tensor Imaging (DTI) has revealed measurable changes in the brains of patients with persistent post-concussive syndrome (PCS). Because of inconsistent results in univariate DTI metrics among patients with mild traumatic brain injury (mTBI), there is currently no single objective and reliable MRI index for clinical decision-making in patients with PCS. Purpose: This study aimed to evaluate the performance of a newly developed PCS Index (PCSI) derived from machine learning of multiparametric magnetic resonance imaging (MRI) data to classify and differentiate subjects with mTBI and PCS history from those without a history of mTBI. Materials and methods: Data were retrospectively extracted from 139 patients aged between 18 and 60 years with PCS who underwent MRI examinations at 2 weeks to 1-year post-mTBI, as well as from 336 subjects without a history of head trauma. The performance of the PCS Index was assessed by comparing 69 patients with a clinical diagnosis of PCS with 264 control subjects. The PCSI values for patients with PCS were compared based on the mechanism of injury, time interval from injury to MRI examination, sex, history of prior concussion, loss of consciousness, and reported symptoms. Results: Injured patients had a mean PCSI value of 0.57, compared to the control group, which had a mean PCSI value of 0.12 (p = 8.42e-23) with accuracy of 88%, sensitivity of 64%, and specificity of 95%, respectively. No statistically significant differences were found in the PCSI values when comparing the mechanism of injury, sex, or loss of consciousness. Conclusion: The PCSI for individuals aged between 18 and 60 years was able to accurately identify patients with post-concussive injuries from 2 weeks to 1-year post-mTBI and differentiate them from the controls. The results of this study suggest that multiparametric MRI-based PCSI has great potential as an objective clinical tool to support the diagnosis, treatment, and follow-up care of patients with post-concussive syndrome. Further research is required to investigate the replicability of this method using other types of clinical MRI scanners.

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OBJECTIVE: Acetylcholinesterase inhibitors (AChEIs) are used off-label, in both adult and pediatric patients, to help further neuro-recovery after traumatic brain injury (TBI). Evidence is limited and piecemeal. This review describes how TBI affects the cholinergic system and consolidates evidence supporting or refuting the use of AChEIs following TBI. METHODS: NCBI MEDLINE search included all articles published through March 2021 on AChEI use in acute and post-acute adult TBI rehabilitation (treatment began <90 days or ≥90 days since injury, respectively), and in pediatric TBI rehabilitation. Further, we checked ClinicalTrials.gov for ongoing trials using AChEIs for TBI rehabilitation in the United States. RESULTS: 27 original articles from NCBI Medline, published through March 2021, were included. The use of AChEIs following TBI in acute and post-acute rehabilitation settings, in both adult and pediatric patients, along with medication side effects, is discussed. CONCLUSIONS: Most studies showed benefits with only moderate effect sizes because of small sample sizes. Reported side effects are minimal and stop soon after AChEIs is discontinued. Conclusions are limited by paucity of research; but fortunately, a large randomized controlled trial is ongoing, and more are needed to truly determine the efficacy of AChEIs in helping with recovery from TBI.

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Aims: To investigate wait time (WT) for chemoradiation and survival in post-op high-grade glioma (HGG) patients admitted to inpatient rehabilitation compared with those discharged home. Materials & methods: A total of 291 HGG patients (14.4% grade III and 84.9% grade IV) were included in this retrospective cohort study. Patients were grouped by disposition following surgery. Results: Median length of stay was longer in acute inpatient rehabilitation facility (AIRF) patients (10d) compared with patients discharged home (3d). AIRF admission was associated with higher odds of excessive treatment delay. Median survival for AIRF patients less than for patients discharged home (42.9 vs 72.71 weeks). WT was not associated with survival even after adjusting for prognostic factors. Conclusion: HGG patients discharged to rehabilitation facilities have longer length of stay, longer WT and shorter survival compared with patients discharged home.

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This comprehensive review discusses clinical studies of patients following brain injuries (traumatic, acquired, or stroke), who have been treated with amantadine or memantine. Both amantadine and memantine are commonly used in the acute rehabilitation setting following brain injuries, despite their lack of FDA-approval for neuro-recovery. Given the broad utilization of such agents, there is a need to review the evidence supporting this common off-label prescribing. The purpose of this review is to describe the mechanisms of action for memantine and amantadine, as well as to complete a comprehensive review of the clinical uses of these agents. We included 119 original, clinical research articles from NCBI Medline, published before 2019. We focused on the domains of neuroplasticity, functional recovery, motor recovery, arousal, fatigue, insomnia, behavior, agitation, and cognition. Most of the existing research supporting the use of amantadine and memantine in recovery from brain injuries was done in very small populations, limiting the significance of conclusions. While most studies are positive; small effect sizes are usually reported, or populations are subject to bias. Furthermore, evidence is so limited that this review includes research regarding both acute and chronic acquired brain injury populations. Fortunately, reported short-term side effects generally are modest, and stop soon after amantadine/memantine is discontinued. However, responses are inconsistent, and the phenotype of responders remains elusive.

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