scholarly journals Prognostic Factors and Pattern of Long-Term Recovery with MLC601 (NeuroAiD™) in the Chinese Medicine NeuroAiD Efficacy on Stroke Recovery - Extension Study

2016 ◽  
Vol 43 (1-2) ◽  
pp. 36-42 ◽  
Author(s):  
Narayanaswamy Venketasubramanian ◽  
Chun Fan Lee ◽  
Sherry H. Young ◽  
San San Tay ◽  
Thirugnanam Umapathi ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Chinese Medicine ◽  
Treatment Effect ◽  
Treatment Time ◽  
Functional Independence ◽  
Stroke Recovery ◽  
Long Term Outcome ◽  
Nihss Score

Background: The Chinese Medicine NeuroAiD Efficacy on Stroke recovery - Extension (CHIMES-E) study is among the few acute stroke trials with long-term outcome data. We aimed to evaluate the recovery pattern and the influence of prognostic factors on treatment effect of MLC601 over 2 years. Methods: The CHIMES-E study evaluated the 2 years outcome of subjects aged ≥18 years with acute ischemic stroke, National Institutes of Health Stroke Scale (NIHSS) score 6-14, pre-stroke modified Rankin Scale (mRS) score ≤1 included in a multicenter, randomized, double-blind, placebo-controlled trial of MLC601 for 3 months. Standard stroke care and rehabilitation were allowed during follow-up with mRS score being assessed in-person at month (M) 3 and by telephone at M1, M6, M12, M18 and M24. Results: Data from 880 subjects were analyzed. There was no difference in baseline characteristics between treatment groups. The proportion of subjects with mRS score 0-1 increased over time in favor of MLC601 most notably from M3 to M6, thereafter remaining stable up to M24, while the proportion deteriorating to mRS score ≥2 remained low at all time points. Older age (p < 0.01), female sex (p = 0.06), higher baseline NIHSS score (p < 0.01) and longer onset to treatment time (OTT; p < 0.01) were found to be predictors of poorer outcome at M3. Greater treatment effect, with more subjects improving on MLC601 than placebo, was seen among subjects with 2 or more prognostic factors (OR 1.65 at M3, 1.78 at M6, 1.90 at M12, 1.65 at M18, 1.39 at M24), especially in subjects with more severe stroke or longer OTT. Conclusions: The sustained benefits of MLC601 over 2 years were due to more subjects improving to functional independence at M6 and beyond compared to placebo. Selection of subjects with poorer prognosis, particularly those with more severe NIHSS score and longer OTT delay, as well as a long follow-up period, may improve the power of future trials investigating the treatment effect of neuroprotective or neurorestorative therapies.

scholarly journals CHInese Medicine NeuroAiD Efficacy on Stroke Recovery - Extension Study (CHIMES-E): A Multicenter Study of Long-Term Efficacy

2015 ◽  
Vol 39 (5-6) ◽  
pp. 309-318 ◽  
Author(s):  
Narayanaswamy Venketasubramanian ◽  
Sherry H. Young ◽  
San San Tay ◽  
Thirugnanam Umapathi ◽  
Annabelle Y. Lao ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Controlled Trial ◽  
Statistical Significance ◽  
Functional Independence ◽  
Stroke Recovery ◽  
Double Blind ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Time Points

Background: The CHInese Medicine NeuroAiD Efficacy on Stroke recovery (CHIMES) study was an international randomized double-blind placebo-controlled trial of MLC601 (NeuroAiD) in subjects with cerebral infarction of intermediate severity within 72 h. CHIMES-E (Extension) aimed at evaluating the effects of the initial 3-month treatment with MLC601 on long-term outcome for up to 2 years. Methods: All subjects randomized in CHIMES were eligible for CHIMES-E. Inclusion criteria for CHIMES were age ≥18, baseline National Institute of Health Stroke Scale of 6-14, and pre-stroke modified Rankin Scale (mRS) ≤1. Initial CHIMES treatment allocation blinding was maintained, although no further study treatment was provided in CHIMES-E. Subjects received standard care and rehabilitation as prescribed by the treating physician. mRS, Barthel Index (BI), and occurrence of medical events were ascertained at months 6, 12, 18, and 24. The primary outcome was mRS at 24 months. Secondary outcomes were mRS and BI at other time points. Results: CHIMES-E included 880 subjects (mean age 61.8 ± 11.3; 36% women). Adjusted OR for mRS ordinal analysis was 1.08 (95% CI 0.85-1.37, p = 0.543) and mRS dichotomy ≤1 was 1.29 (95% CI 0.96-1.74, p = 0.093) at 24 months. However, the treatment effect was significantly in favor of MLC601 for mRS dichotomy ≤1 at 6 months (OR 1.49, 95% CI 1.11-2.01, p = 0.008), 12 months (OR 1.41, 95% CI 1.05-1.90, p = 0.023), and 18 months (OR 1.36, 95% CI 1.01-1.83, p = 0.045), and for BI dichotomy ≥95 at 6 months (OR 1.55, 95% CI 1.14-2.10, p = 0.005) but not at other time points. Subgroup analyses showed no treatment heterogeneity. Rates of death and occurrence of vascular and other medical events were similar between groups. Conclusions: While the benefits of a 3-month treatment with MLC601 did not reach statistical significance for the primary endpoint at 2 years, the odds of functional independence defined as mRS ≤1 was significantly increased at 6 months and persisted up to 18 months after a stroke.

Optimal thresholds to predict long-term outcome after complete endovascular recanalization in acute anterior ischemic stroke

2021 ◽  
pp. neurintsurg-2020-016997
Author(s):  
Ulf Neuberger ◽  
Philipp Vollmuth ◽  
Simon Nagel ◽  
Silvia Schönenberger ◽  
Charlotte Sabine Weyland ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Predictive Performance ◽  
Functional Independence ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Nihss Score ◽  
Endovascular Recanalization ◽  
Optimal Thresholds

BackgroundDespite complete endovascular recanalization, a significant percentage of patients with acute anterior stroke do not achieve a good clinical outcome. We analyzed optimal thresholds of relevant parameters to discern functional independence after successful endovascular recanalization and test their predictive performance.MethodsPatients with acute anterior ischemic stroke undergoing endovascular treatment between April 2015 and November 2019 were retrospectively analyzed. Only patients with premorbid modified Rankin Scale (mRS) score <3 and complete recanalization (modified Thrombolysis In Cerebral Infarction 2c/3) were included. Optimal thresholds of the most important variables predicting functional independence (mRS 0–2 after 90 days) were calculated using receiver operating characteristic curves and their predictive performance was tested in an independent dataset using machine learning algorithms.ResultsOverall, 371 patients met the inclusion criteria. Optimal thresholds for the overall most important variables to predict functional independence were (1) National Institutes of Health Stroke Scale (NIHSS) score ≤5 after 24 hours (area under the curve (AUC) 0.88 (95% CI 0.84 to 0.92)); (2) Alberta Stroke Program Early CT Score (ASPECTS) ≥7 on follow-up CT (AUC 0.72 (95% CI 0.68 to 0.77)); and (3) change in NIHSS score ≥8 after 24 hours (AUC 0.70 (95% CI 0.65 to 0.74)). The performance of these thresholds to predict a good outcome using machine learning in the independent dataset was evaluated for (1) NIHSS score ≤5 after 24 hours (AUC 0.76 (95% CI 0.71 to 0.81)); (2) follow-up ASPECTS ≥7 (AUC 0.64 (95% CI 0.58 to 0.70)); (3) change in NIHSS score ≥8 after 24 hours (AUC 0.61 (95% CI 0.55 to 0.67)); and (4) the combination of all three parameters (AUC 0.84 (95% CI 0.80 to 0.88)).ConclusionsAfter complete recanalization in acute anterior circulation ischemic stroke, a good long-term outcome could be accurately predicted reaching NIHSS score ≤5 after 24 hours.

Prognostic Factors and Long-Term Outcome with ANCA-Associated Kidney Vasculitis in Childhood

2021 ◽  
pp. CJN.19181220
Author(s):  
Marta Calatroni ◽  
Filippo Consonni ◽  
Marco Allinovi ◽  
Alessandra Bettiol ◽  
Natasha Jawa ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Kidney Failure ◽  
Prognostic Significance ◽  
Remission Induction ◽  
Long Term Outcome ◽  
Anca Associated Vasculitis ◽  
Kidney Involvement ◽  
Ckd Stage

Background and objectives. Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is extremely rare in children. We report the clinico-pathological features, long-term outcomes, and prognostic factors of a large paediatric cohort of patients with ANCA-associated kidney vasculitis. Design, setting, participants, and measurements. This retrospective study included 85 consecutive patients with kidney biopsy-proven ANCA-associated vasculitis followed at tertiary referral centres in Italy and Canada. Kidney biopsies were categorised as focal, crescentic, sclerotic or mixed following Berden's classification. The prognostic significance of baseline clinical, laboratory and histological findings was analysed with respect to kidney failure or chronic kidney disease (CKD) 3-5/kidney failure. Results. Fifty-three patients had microscopic polyangiitis (62%) and 32 granulomatosis with polyangiitis (38%). Rapidly progressive glomerulonephritis was the most frequent presentation (39%); one third of the patients also had nephrotic-range proteinuria. Kidney biopsies were classified as focal in 21% of the patients, crescentic in 51%, sclerotic in 15% and mixed in 13%. Remission-induction therapies included cyclophosphamide in 78% of cases. Twenty-five patients (29%) reached kidney failure. The median time to kidney failure or last follow-up was 35 months (6-89) in the whole cohort, and 73 months (24-109) among the patients who did not reach this outcome. Cases with sclerotic histology showed significantly shorter kidney survival [HR 11.80 (95% CI 2.49-55.99)] and CKD 3-5-free survival [HR 8.88 (95% CI 2.43-32.48)] as compared with focal/mixed ones. Baseline eGFR, low serum albumin, hypertension, central nervous system complications and sclerotic histology, which reflected severe kidney involvement, were associated with both kidney failure or CKD stage 3-5/kidney failure at unadjusted analysis; no independent prognostic factors emerged at multivariate analysis. Conclusions. Children with ANCA-associated kidney vasculitis often have aggressive presentation; one-third of them progress to kidney failure and usually do so early during the follow-up. A severe renal presentation is associated with the development of CKD or kidney failure.

Long-Term Outcome after Immunosuppressive Therapy with Rabbit ΑΤG for Pediatric Aplastic Anemia: A Single-Center Retrospective Study in China

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2678-2678
Author(s):  
Jingliao Zhang ◽  
Lixian Chang ◽  
Ye Guo ◽  
Yingchi Zhang ◽  
Tianfeng Liu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Response Rate ◽  
First Line ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Free Survival ◽  
Time Points

Abstract Background: Antithymocyte globulin (ATG)-based immunosuppressive therapy (IST) has been successfully used as the first-line treatment for severe / very severe aplastic anemia (SAA/VSAA) patients if no HLA-matched sibling donor was eligible for HSCT as a first choice. It was reported rabbit ATG (rATG) produced more profound immunosuppressive activity compared to horse ATG (hATG). However, recent clinical studies indicated that the stronger lympholytic activity did not mean that rATG was more effective. Most experiences from adult SAA/VSAA implied the efficacy of rATG was worse than hATG. However, susceptibility of children to intensive IST might not be exactly the same as adult patients, long-term efficacy of rATG in historic studies for children with SAA/VSAA was still elusive. Purpose: This study includes the largest cohort of pediatric AA patients treated with first-line rATG+CSA regimen published to date after a median follow-up of 69 months, aiming to assess the long-term outcome of rATG for children, and to identify the significant prior factors in clinical decision making. Methods: We reviewed 231 SAA/VSAA patients under 18 years old assigned to rATG+CSA from February 2000 to May 2014 in Department of Pediatrics, the Blood Diseases Hospital & Institute of Hematology, CAMS & PUMC. Response was evaluated 3, 6, 9, 12 24, 36 and 60 months after IST. We separately defined SAA-II as a specific type of gradually progressed SAA from a NSAA status within a longer period for at least 6 months. Multivariate logistic regression models were used to evaluate the effects of variables on the responses at different time points. Multivariate Cox model analysis of overall survival (OS) and failure-free survival (FFS) was calculated for variables with a log rank P value less than 0.1 in Kaplan-Meier analysis. Results: Of the overall patients, the total responded patients were 79(34.3%), 110(51.6%), and 129 (60.6%) at 6, 9, 12 months following IST, respectively. Intriguingly, 22 patients achieved delayed response between 12 months and 24months after IST, which increased the overall response rate by 10.2%, afterwards the rate reached a plateau by 3 years with the best response rate of 74.6% (Figure 1). Differences in baseline clinical parameters pre-IST were associated with response to IST. Absolute neutrophil count (ANC) less than 0.1*109/L was associated with an unfavorable early response rate at 6 months (P=0.009); absolute lymphocyte count (ALC) less than 1.6*109/L was a significant predictor for better response by 6 months and 12 months in multivariate analysis [6 months, P=0.033 vs. 12 months, P=0.021]. Lower absolute reticulocyte count (ARC no more than 18.5*109/L) predicted worse late IST response by 2 years and 3 years. In our large series of cohort, 5-year OS and FFS were 82.7% and 61.9%. Patients with VSAA as a significantly unfavorable prognostic factor had a much lower probability of 5-year survival when compared to patients diagnosed with SAA (76.4% vs. 87.2%, P<0.001, Figure2A). In multivariate analysis, SAA-II (P=0.021, Figure2B), and a pretreatment lower ARC (P=0.020, Figure2C) were independent unfavorable prognostic factors for FFS, but moderate PNH clone size (more than 5%) was verified as a good predictor for FFS (P=0.006, Figure 2D). At the last follow-up, twelve of the 135 responders relapsed after IST, meanwhile eight patients in responders and seven patients in non-responders experienced clonal evolution after IST, corresponding to cumulative incidences at 5.2% of relapse and 6.5% of evolution, which were obviously lower than previous reports. Conclusions: The combination of rATG and CSA was confirmed as an effective first-line therapy for children with SAA/VSAA in our cohort. We discerned a protracted recovery but an ultimately comparable long-term outcome of rATG. Baseline blood parameters (ANC, ALC, ARC) were predictive factors of response rate. Intensive supportive care may be necessarily pivotal to survival in cases of VSAA. Importantly, moderate PNH clone might be beneficial to FFS. Besides, for those who experienced gradually progressed disease course, early HSCT might be a more preferable option than receiving IST although further validation remains to be done. Figure 1 Overall efficacy at different time points following IST initiation Figure 1. Overall efficacy at different time points following IST initiation Figure 2 Prognostic factors for overall survival (OS) and failure-free survival (FFS) Figure 2. Prognostic factors for overall survival (OS) and failure-free survival (FFS) Disclosures No relevant conflicts of interest to declare.

scholarly journals Long-term outcome of endovascular therapy for acute basilar artery occlusion

2020 ◽  
pp. 0271678X2095858
Author(s):  
Longfei Wu ◽  
Da Zhang ◽  
Jian Chen ◽  
Chenghe Sun ◽  
Kangxiang Ji ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Artery Occlusion ◽  
Favorable Outcome ◽  
Basilar Artery Occlusion ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Factors Associated ◽  
Long Term Follow Up

The long-term functional outcome of acute basilar artery occlusion (BAO) patients who received modern endovascular therapy (EVT) is unclear. We sought to assess the long-term functional outcome of BAO patients treated with EVT and determine the prognostic factors associated with favorable outcome. We enrolled consecutive BAO patients who received EVT between December 2012 and December 2018 in this observational study. Baseline characteristics and outcomes were presented. Multivariable logistic regression analysis was performed to identify the prognostic factors associated with long-term outcome. Among the 177 BAO patients included in this study, 80 patients (45.2%) obtained favorable outcome and 97 patients (54.8%) had unfavorable outcome at long-term follow-up with a median observation time of 12 months (interquartile range, 3–19). A total of 67 patients (37.9%) died. National Institutes of Health Stroke Scale (NIHSS), posterior circulation Alberta Stroke Program Early Computed Tomography Score (pc-ASPECTS), time from stroke onset to recanalization, and recanalization condition were identified as independent predictors for long-term outcome. Over 40% of BAO patients who were treated with modern EVT achieved favorable outcome at long-term follow-up. NIHSS, pc-ASPECTS, time from stroke onset to recanalization, and recanalization condition were identified as independent prognostic factors of long-term outcome.

Long-term results of salvage endoscopic treatment for patients with local failure after chemoradiotherapy for esophageal squamous cell carcinoma.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 207-207
Author(s):  
Ken Hatogai ◽  
Tomonori Yano ◽  
Takashi Kojima ◽  
Masakatsu Onozawa ◽  
Toshihiko Doi ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Prognostic Factors ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Local Failure ◽  
Long Term Results ◽  
Long Term Outcome

207 Background: Local failure is a major problem after chemoradiotherapy (CRT) in patients with esophageal squamous cell carcinoma (ESCC), and salvage surgery presents high morbidity and mortality rates. We have introduced photodynamic therapy (PDT) and endoscopic resection (ER) for local failures to develop a less invasive salvage treatment.The aim of this retrospective study was to clarify the long-term outcome of salvage endoscopic treatments (SET). Methods: Between 1998 and 2008, 716 patients with ESCC were treated with definitive CRT in our institution. There were 314 patients with incomplete response and 103 with local recurrence after achieving complete response (CR) once. The indication criteria of SET were as follows: 1) absence of lymph node and distant metastasis and 2) local failures limited within T2. ER was performed for local failures limited to T1b (SM1), and PDT was performed for lesions invading T1b (SM2) or T2, in patients who could not tolerate or who refused surgery. We assessed overall survival (OS), relapse-free survival (RFS), and also prognostic factors. This study was approved by an institutional review board. Results: A total of 164 patients with local failure underwent SET (ER: 58, PDT: 106). The characteristics before CRT were as follows: T1/2/3/4, 44/25/75/20; N0/1, 85/79; stage I/II/III/IV, 35/59/57/13; and those of before SET were as follows: T1/2, 126/38; residue/recurrence, 76/88. ER achieved curative resection in 51 (87.9%), and PDT achieved CR in 61 (57.5%) patients. With a median follow up period of 73 months, the OS and RFS rates at 5 years from SET were 38.6% (95% CI 31.0–46.2) and 28.1% (95% CI 21.0–35.2). Multivariate analysis revealed 2 preferable prognostic factors in common for OS and RFS, N0 before CRT (OS HR: 0.47 [95% CI 0.32–0.69], RFS HR: 0.61 [95%CI 0.43–0.87]) and a period from initiation of CRT to SET longer than 6 months (OS HR: 0.57 [95%CI 0.39–0.84], RFS HR: 0.67 [0.47–0.95]). After 5 years of follow up, 58 patients (35.4%) were alive without any metastasis under esophagus preservation. Conclusions: SET demonstrated a favorable outcome in an analysis of a large number of patients with local failure after definitive CRT for ESCC.

Surgery for intramedullary spinal cord ependymomas in the neuromonitoring era: results from a consecutive series of 100 patients

2021 ◽  
pp. 1-11
Author(s):  
Benjamin Skrap ◽  
Vincenzo Tramontano ◽  
Franco Faccioli ◽  
Mario Meglio ◽  
Giampietro Pinna ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Evoked Potentials ◽  
Functional Independence ◽  
Learning Curves ◽  
Consecutive Series ◽  
Intramedullary Spinal Cord ◽  
Long Term Outcome ◽  
D Wave

OBJECTIVE The established treatment of intramedullary spinal cord ependymomas (ISCEs) is resection. Surgical series reporting treatment results often lack homogeneity, as these are collected over long time spans and their analysis is plagued by surgical learning curves and inconsistent use of intraoperative neurophysiological monitoring (IONM). The authors report the oncological and functional long-term outcomes in a modern series of 100 consecutive ISCEs that were resected between 2000 and 2015 by a surgically experienced team that consistently utilized IONM. METHODS In this retrospective study, the authors tailored surgical strategy and multimodal IONM, including somatosensory evoked potentials, muscle motor evoked potentials (mMEPs), and D-waves, with the aim of gross-total resection (GTR). Preservation of the D-wave was the primary objective, and preservation of mMEPs was the second functional objective. Functional status was evaluated using the modified McCormick Scale (MMS) preoperatively, postoperatively, and at follow-up. RESULTS Preoperatively, 89 patients were functionally independent (MMS grade I or II). A GTR was achieved in 89 patients, 10 patients had a stable residual, and 1 patient underwent reoperation for tumor progression. At a mean follow-up of 65.4 months, 82 patients were functionally independent, and 11 lost their functional independence after surgery (MMS grades III–V). Muscle MEP loss predicted short-term postoperative worsening (p < 0.0001) only, while the strongest predictors of a good functional long-term outcome were lower preoperative MMS grades (p < 0.0001) and D-wave preservation. D-wave monitorability was 67%; it was higher with lower preoperative MMS grades and predicted a better recovery (p = 0.01). CONCLUSIONS In this large series of ISCEs, a high rate of GTR and long-term favorable functional outcome were achieved. Short- and long-term functional outcomes were best reflected by mMEPs and D-wave monitoring, respectively.

scholarly journals Effect of Combined Treatment with MLC601 (NeuroAiDTM) and Rehabilitation on Post-Stroke Recovery: The CHIMES and CHIMES-E Studies

2018 ◽  
Vol 46 (1-2) ◽  
pp. 82-88 ◽  
Author(s):  
Nijasri C. Suwanwela ◽  
Christopher L.H. Chen ◽  
Chun Fan Lee ◽  
Sherry H. Young ◽  
San San Tay ◽  
...  
Keyword(s):  
Treatment Effect ◽  
Treatment Time ◽  
Controlled Trial ◽  
Combined Treatment ◽  
Functional Independence ◽  
Stroke Recovery ◽  
Double Blind ◽  
Stroke Treatment ◽  
Rehabilitation Programs ◽  
Sustained Effects

Background and Purpose: MLC601 has been shown in preclinical studies to enhance neurorestorative mechanisms after stroke. The aim of this post hoc analysis was to assess whether combining MLC601 and rehabilitation has an effect on improving functional outcomes after stroke. Methods: Data from the CHInese Medicine NeuroAiD Efficacy on Stroke (CHIMES) and CHIMES-Extension (CHIMES-E) studies were analyzed. CHIMES-E was a 24-month follow-up study of subjects included in CHIMES, a multi-centre, double-blind placebo-controlled trial which randomized subjects with acute ischemic stroke, to either MLC601 or placebo for 3 months in addition to standard stroke treatment and rehabilitation. Subjects were stratified according to whether they received or did not receive persistent rehabilitation up to month (M)3 (non- randomized allocation) and by treatment group. The modified Rankin Scale (mRS) and Barthel Index were assessed at month (M) 3, M6, M12, M18, and M24. Results: Of 880 subjects in CHIMES-E, data on rehabilitation at M3 were available in 807 (91.7%, mean age 61.8 ± 11.3 years, 36% female). After adjusting for prognostic factors of poor outcome (age, sex, pre-stroke mRS, baseline National Institute of Health Stroke Scale, and stroke onset-to-study-treatment time), subjects who received persistent rehabilitation showed consistently higher treatment effect in favor of MLC601 for all time points on mRS 0–1 dichotomy analysis (ORs 1.85 at M3, 2.18 at M6, 2.42 at M12, 1.94 at M18, 1.87 at M24), mRS ordinal analysis (ORs 1.37 at M3, 1.40 at M6, 1.53 at M12, 1.50 at M18, 1.38 at M24), and BI ≥95 dichotomy analysis (ORs 1.39 at M3, 1.95 at M6, 1.56 at M12, 1.56 at M18, 1.46 at M24) compared to those who did not receive persistent rehabilitation. Conclusions: More subjects on MLC601 improved to functional independence compared to placebo among subjects receiving persistent rehabilitation up to M3. The larger treatment effect of MLC601 was sustained over 2 years which supports the hypothesis that MLC601 combined with rehabilitation might have beneficial and sustained effects on neuro-repair processes after stroke. There is a need for more data on the effect of combining rehabilitation programs with stroke recovery treatments.

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