scholarly journals Biomarker-based patient selection improves stroke rehabilitation trial efficiency

2018 ◽  
Author(s):  
Cathy M. Stinear ◽  
Winston D. Byblow ◽  
P. Alan Barber ◽  
Suzanne J. Ackerley ◽  
Marie-Claire Smith ◽  
...  

AbstractBackground and PurposeInter-subject variability complicates trials of novel stroke rehabilitation therapies, particularly in the sub-acute phase after stroke. We tested whether selecting patients using motor evoked potential (MEP) status, a physiological biomarker of motor system function, could improve trial efficiency.MethodsA retrospective analysis of data from 207 patients (103 women, mean (SD) 70.6 (15.1) years) was used to estimate sample sizes and recruitment rates required to detect a 7-point difference between hypothetical control and treatment groups in upper-limb Fugl-Meyer and Action Research Arm Test scores at 90 days post-stroke. Analyses were carried out for the full sample and for subsets defined by motor evoked potential (MEP) status.ResultsSelecting patients according to MEP status reduced the required sample size by 75% compared to an unselected sample. The estimated time needed to recruit the required sample was also reduced by 72% for patients with MEPs, and was increased by 2-3-fold for patients without MEPs.ConclusionsUsing biomarkers to select patients can improve stroke rehabilitation trial efficiency by reducing the sample size and recruitment time needed to detect a clinically meaningful effect of the tested intervention.

Author(s):  
Leatha A Clark ◽  
Todd M Manini ◽  
Nathan P Wages ◽  
Janet E Simon ◽  
David W Russ ◽  
...  

Abstract Background Weakness is a risk factor for physical limitations and death in older adults (OAs). We sought to determine whether OAs with clinically meaningful leg extensor weakness exhibit differences in voluntary inactivation (VIA) and measures of corticospinal excitability when compared to young adults (YAs) and OAs without clinically meaningful weakness. We also sought to estimate the relative contribution of indices of neural excitability and thigh lean mass in explaining the between-subject variability in OAs leg extensor strength. Methods In 66 OAs (75.1 ± 7.0 years) and 20 YAs (22.0 ± 1.9 years), we quantified leg extensor strength, thigh lean mass, VIA, and motor evoked potential (MEP) amplitude and silent period (SP) duration. OAs were classified into weakness groups based on previously established strength/body weight (BW) cut points (Weak, Modestly Weak, or Not Weak). Results The OAs had 63% less strength/BW when compared to YAs. Weak OAs exhibited higher levels of leg extensor VIA than Not Weak OAs (14.2 ± 7.5% vs 6.1 ± 7.5%). Weak OAs exhibited 24% longer SPs compared to Not Weak OAs, although this difference was insignificant (p = .06). The Weak OAs MEPs were half the amplitude of the Not Weak OAs. Regression analysis indicated that MEP amplitude, SP duration, and thigh lean mass explained ~62% of the variance in strength, with the neural excitability variables explaining ~33% of the variance and thigh lean mass explaining ~29%. Conclusion These findings suggest that neurotherapeutic interventions targeting excitability could be a viable approach to increase muscle strength in order to reduce the risk of physical impairments in late life.


2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Davide Giampiccolo ◽  
Cristiano Parisi ◽  
Pietro Meneghelli ◽  
Vincenzo Tramontano ◽  
Federica Basaldella ◽  
...  

Abstract Muscle motor-evoked potentials are commonly monitored during brain tumour surgery in motor areas, as these are assumed to reflect the integrity of descending motor pathways, including the corticospinal tract. However, while the loss of muscle motor-evoked potentials at the end of surgery is associated with long-term motor deficits (muscle motor-evoked potential-related deficits), there is increasing evidence that motor deficit can occur despite no change in muscle motor-evoked potentials (muscle motor-evoked potential-unrelated deficits), particularly after surgery of non-primary regions involved in motor control. In this study, we aimed to investigate the incidence of muscle motor-evoked potential-unrelated deficits and to identify the associated brain regions. We retrospectively reviewed 125 consecutive patients who underwent surgery for peri-Rolandic lesions using intra-operative neurophysiological monitoring. Intraoperative changes in muscle motor-evoked potentials were correlated with motor outcome, assessed by the Medical Research Council scale. We performed voxel–lesion–symptom mapping to identify which resected regions were associated with short- and long-term muscle motor-evoked potential-associated motor deficits. Muscle motor-evoked potentials reductions significantly predicted long-term motor deficits. However, in more than half of the patients who experienced long-term deficits (12/22 patients), no muscle motor-evoked potential reduction was reported during surgery. Lesion analysis showed that muscle motor-evoked potential-related long-term motor deficits were associated with direct or ischaemic damage to the corticospinal tract, whereas muscle motor-evoked potential-unrelated deficits occurred when supplementary motor areas were resected in conjunction with dorsal premotor regions and the anterior cingulate. Our results indicate that long-term motor deficits unrelated to the corticospinal tract can occur more often than currently reported. As these deficits cannot be predicted by muscle motor-evoked potentials, a combination of awake and/or novel asleep techniques other than muscle motor-evoked potentials monitoring should be implemented.


2021 ◽  
pp. 1-8
Author(s):  
Hao You ◽  
Xing Fan ◽  
Jiajia Liu ◽  
Dongze Guo ◽  
Zhibao Li ◽  
...  

OBJECTIVE The current study investigated the correlation between intraoperative motor evoked potential (MEP) and somatosensory evoked potential (SSEP) monitoring and both short-term and long-term motor outcomes in aneurysm patients treated with surgical clipping. Moreover, the authors provide a relatively optimal neurophysiological predictor of postoperative motor deficits (PMDs) in patients with ruptured and unruptured aneurysms. METHODS A total of 1017 patients (216 with ruptured aneurysms and 801 with unruptured aneurysms) were included. Patient demographic characteristics, clinical features, intraoperative monitoring data, and follow-up data were retrospectively reviewed. The efficacy of using changes in MEP/SSEP to predict PMDs was assessed using binary logistic regression analysis. Subsequently, receiver operating characteristic curve analysis was performed to determine the optimal critical value for duration of MEP/SSEP deterioration. RESULTS Both intraoperative MEP and SSEP monitoring were significantly effective for predicting short-term (p < 0.001 for both) and long-term (p < 0.001 for both) PMDs in aneurysm patients. The critical values for predicting short-term PMDs were amplitude decrease rates of 57.30% for MEP (p < 0.001 and area under the curve [AUC] 0.732) and 64.10% for SSEP (p < 0.001 and AUC 0.653). In patients with an unruptured aneurysm, the optimal critical values for predicting short-term PMDs were durations of deterioration of 17 minutes for MEP (p < 0.001 and AUC 0.768) and 21 minutes for SSEP (p < 0.001 and AUC 0.843). In patients with a ruptured aneurysm, the optimal critical values for predicting short-term PMDs were durations of deterioration of 12.5 minutes for MEP (p = 0.028 and AUC 0.706) and 11 minutes for SSEP (p = 0.043 and AUC 0.813). CONCLUSIONS The authors found that both intraoperative MEP and SSEP monitoring are useful for predicting short-term and long-term PMDs in patients with unruptured and ruptured aneurysms. The optimal intraoperative neuromonitoring method for predicting PMDs varies depending on whether the aneurysm has ruptured or not.


2018 ◽  
Vol 128 (1) ◽  
pp. 56-61 ◽  
Author(s):  
Kareem O. Tawfik ◽  
Zoe A. Walters ◽  
Gavriel D. Kohlberg ◽  
Noga Lipschitz ◽  
Joseph T. Breen ◽  
...  

Objectives: Assess the utility of intraoperative transcranial facial motor-evoked potential (FMEP) monitoring in predicting and improving facial function after vestibular schwannoma (VS) resection. Study Design: Retrospective chart review. Methods: Data were obtained from 82 consecutive VS resections meeting inclusion criteria. Sixty-two cases were performed without FMEP and 20 with FMEP. Degradation of FMEP response was defined as a final-to-baseline amplitude ratio of 0.5 or less. House-Brackmann (HB) grade was assessed preoperatively, postoperatively, at follow-up assessments, and it was compared between pre- and post-FMEP cohorts. Positive predictive value (PPV) and negative predictive value (NPV), sensitivity, and specificity of FMEP degradation in predicting facial weakness were calculated. Results: In the pre-FMEP group, at length of follow-up (LOF) ⩾9 months, 83.9% (52/62) of patients exhibited HB 1-2 outcome. In the post-FMEP cohort, 75.0% (15/20) exhibited HB 1-2 function at LOF ⩾9 months. There was no difference in rates of HB 1-2 outcomes between groups in the immediate postoperative period ( P = .35) or at long-term follow-up ( P = 1.0). With respect to predicting immediate postoperative facial function, FMEP demonstrated high specificity (88.9%) and moderate sensitivity (54.5%). The PPV and NPV for immediate postoperative facial function were 85.7% and 61.5%, respectively. With respect to long-term (⩾9 months LOF) facial function, intraoperative FMEP was moderately sensitive (71.4%) and highly specific (84.6%); PPV was moderate (71.4%), and NPV was high (84.6%). Conclusions: Intraoperative FMEP is highly specific and moderately sensitive in predicting postoperative facial function for patients undergoing VS resection, but its use may not be associated with improved facial nerve outcomes. Level of Evidence: 4


2018 ◽  
Vol 57 ◽  
pp. 105-110
Author(s):  
Takeru Umemura ◽  
Shigeru Nishizawa ◽  
Yoshiteru Nakano ◽  
Takeshi Saito ◽  
Takehiro Kitagawa ◽  
...  

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