Neural Interface-Based Motor Neuroprosthesis in Poststroke Upper Limb Neurorehabilitation: An Individual Patient Data Meta-analysis.

OBJECTIVE: To determine the efficacy of neural interface-based neurorehabilitation, including brain-computer interface, through conventional and individual patient data (IPD) meta-analysis and to assess clinical parameters associated with positive response to neural interface-based neurorehabilitation. DATA SOURCES: PubMed, EMBASE, and Cochrane Library databases up to February 2022 were reviewed. STUDY SELECTION: Studies using neural interface-controlled physical effectors (functional electrical stimulation and/or powered exoskeletons) and reported Fugl-Meyer Assessment-upper-extremity (FMA-UE) scores were identified. This meta-analysis was prospectively registered on PROSPERO (#CRD42022312428). PRISMA guidelines were followed. DATA EXTRACTION: Changes in FMA-UE scores were pooled to estimate the mean effect size. Subgroup analyses were performed on clinical parameters and neural interface parameters with both study-level variables and IPD. DATA SYNTHESIS: Forty-six studies containing 617 patients were included. Twenty-nine studies involving 214 patients reported IPD. FMA-UE scores increased by a mean of 5.23 (95% confidence interval [CI]: 3.85-6.61). Systems that used motor attempt resulted in greater FMA-UE gain than motor imagery, as did training lasting >4 vs ≤4 weeks. On IPD analysis, the mean time-to-improvement above minimal clinically important difference (MCID) was 12 weeks (95% CI: 7 to not reached). At 6 months, 58% improved above MCID (95% CI: 41%-70%). Patients with severe impairment (P=.042) and age >50 years (P=.0022) correlated with the failure to improve above the MCID on univariate log-rank tests. However, these factors were only borderline significant on multivariate Cox analysis (hazard ratio [HR] 0.15, P=.08 and HR 0.47, P=.06, respectively). CONCLUSION: Neural interface-based motor rehabilitation resulted in significant, although modest, reductions in poststroke impairment and should be considered for wider applications in stroke neurorehabilitation.

Modeling the Properties of White Matter Tracts Using Diffusion Tensor Imaging to Characterize Patterns of Injury in Aging and Neurodegenerative Disease.

Diffusion tensor imaging (DTI) is a relatively novel magnetic resonance-based imaging methodology that can provide valuable insight into the microstructure of white matter tracts of the brain. In this paper, we evaluated the reliability and reproducibility of deriving a semi-automated pseudo-atlas DTI tractography method vs. standard atlas-based analysis alternatives, for use in clinical cohorts with neurodegeneration and ventriculomegaly. We showed that the semi-automated pseudo-atlas DTI tractography method was reliable and reproducible across different cohorts, generating 97.7% of all tracts. However, DTI metrics obtained from both methods were significantly different across the majority of cohorts and white matter tracts (p < 0.001). Despite this, we showed that both methods produced patterns of white matter injury that are consistent with findings reported in the literature and with DTI profiles generated from these methodologies. Scatter plots comparing DTI metrics obtained from each methodology showed that the pseudo-atlas method produced metrics that implied a more preserved neural structure compared to its counterpart. When comparing DTI metrics against a measure of ventriculomegaly (i.e., Evans' Index), we showed that the standard atlas-based method was able to detect decreasing white matter integrity with increasing ventriculomegaly, while in contrast, metrics obtained using the pseudo-atlas method were sensitive for stretch or compression in the posterior limb of the internal capsule. Additionally, both methods were able to show an increase in white matter disruption with increasing ventriculomegaly, with the pseudo-atlas method showing less variability and more specificity to changes in white matter tracts near to the ventricles. In this study, we found that there was no true gold-standard for DTI methodologies or atlases. Whilst there was no congruence between absolute values from DTI metrics, differing DTI methodologies were still valid but must be appreciated to be variably sensitive to different changes within white matter injury occurring concurrently. By combining both atlas and pseudo-atlas based methodologies with DTI profiles, it was possible to navigate past such challenges to describe white matter injury changes in the context of confounders, such as neurodegenerative disease and ventricular enlargement, with transparency and consistency.

Incidence of biomarkers in high-grade gliomas and their impact on survival in a diverse SouthEast Asian cohort - a population-based study.

BACKGROUND: Gliomas consist of a heterogeneous group of tumors. This study aimed to report the incidences of O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation, 1p19q co-deletion, isocitrate dehydrogenase (IDH) gene mutations, and inactivating mutations of alpha-thalassemia/mental retardation syndrome X-linked (ATRX) in high-grade gliomas in an ethnically diverse population. METHODS: Records of patients who underwent surgery for high-grade gliomas from January 2013 to March 2017 at our institution were obtained. The patients' age, gender, ethnicity, Karnofsky Performance Scale (KPS) score, ability to perform activities of daily living (ADLs), tumor location and biomarkers status were recorded. Data were analyzed using chi-square and Mann-Whitney U tests, Kaplan-Meier estimates and log-rank test. RESULTS: 181 patients were selected (56 with grade III gliomas, 125 with grade IV gliomas). In the grade III group, 55% had MGMT promoter methylation, 41% had 1p19q co-deletion, 35% had IDH1 mutation and none had ATRX loss. In the grade IV group, 30% had MGMT promoter methylation, 2% had 1p19q co-deletion, 15% had IDH1 mutation and 8% had ATRX loss. After adjusting for effects of age, surgery and pre-operative ADL statuses, only MGMT promoter methylation was found to be significantly associated with longer overall survival time in grade III (p = 0.024) and IV patients (p = 0.006). CONCLUSIONS: The incidences of MGMT promoter methylation and IDH1 mutation were found to be comparable to globally reported rates, but those of 1p19q co-deletion and ATRX loss seemed to be lower in our cohort. MGMT promoter methylation was associated with increased overall survival in our cohort and might serve as favorable prognostic factor.

Effects of surgery on neurocognitive function in patients with glioma: a meta-analysis of immediate post-operative and long-term follow-up neurocognitive outcomes.

PURPOSE: This study aims to identify the neuropsychological tests commonly used for assessment in each neurocognitive domain, and quantify the post-operative changes in neurocognitive function in the immediate post-operation and follow-up. METHODS: With the use of the PubMed, a comprehensive search of the English literature was performed following PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. There were 1021 publications identified for screening. Standardized mean differences (SMD) in neuropsychological task performance were calculated both for immediate post-operation (up to 1 week) and follow-up (up to 6 months). RESULTS: Out of 12 studies which met the inclusion criteria, 11 studies were analyzed in this meta-analysis, with a total of 313 patients (age range 18-82, 50% males) with intracranial gliomas (45% high-grade, 55% low-grade). Complex attention, language and executive function were the most frequently tested neurocognitive domains. Surgery had a positive impact in the domains of complex attention, language, learning and memory tasks in the immediate post-operative period and sustained improvement at follow-up. In contrast, surgery was found to negatively impact performance for executive function in the immediate post-operative period with sustained decline in performance in the long term. CONCLUSIONS: This meta-analysis suggests that surgery for glioma confers a benefit for the domains of complex attention, language, learning and memory, while negatively affecting executive function, in the periods immediately after surgery and at 6 months follow-up. In addition, awake surgery seemed to confer a beneficial effect on neurocognitive functions. Future research should attempt to standardize a battery of neuropsychological tests for patients undergoing surgical resection for glioma, perhaps with a particular focus on executive function.