Pulse-burst spontaneous Raman thermometry of unsteady wave phenomena in a shock tube.

A high-speed temperature diagnostic based on spontaneous Raman scattering (SRS) was demonstrated using a pulse-burst laser. The technique was first benchmarked in near-adiabatic ${{\rm H}_2} \text{-} {\rm air}$ flames at a data-acquisition rate of 5 kHz using an integrated pulse energy of 1.0 J per realization. Both the measurement precision and accuracy in the flame were within 3% of adiabatic predictions. This technique was then evaluated in a challenging free-piston shock tube environment operated at a shock Mach number of 3.5. SRS thermometry resolved the temperature in post-incident and post-reflected shock flows at a repetition rate of 3 kHz and clearly showed cooling associated with driver expansion waves. Collectively, this Letter represents a major advancement for SRS in impulsive facilities, which had previously been limited to steady state regions or single-shot acquisition.

Impact of clinical severity of stroke on the severity and recovery of visuospatial neglect.

BACKGROUND AND PURPOSE: There is growing evidence that visuospatial neglect (VSN) is associated with lower functional performance in other modalities and is not restricted to the lesioned hemisphere alone, and may also affect the non-lesioned hemisphere in severe first-ever strokes. We aimed to investigate the longitudinal association between the severity of VSN, as reflected by the extent of ipsilesional and contralesional spatial attention deficit, and clinical severity of stroke. METHODS: This is a secondary data analysis with merged data from two prospective cohort studies. Resulting in 90 patients and 8 longitudinal measurements at 1, 2, 3, 4, 5, 8, 12, and 26 weeks post-stroke onset. A letter cancellation test (LCT) was used as the primary outcome measure to demonstrate presence and severity of VSN. The clinical severity of stroke was classified using the Bamford Classification. RESULTS: No significant association between clinical severity and the number of ipsilesional, as well as contralesional, omissions on the LCT was observed. Recovery of VSN at the contralesional hemiplegic, as well as ipsilesional non-hemiplegic side, was only dependent on 'time' as a reflection of spontaneous neurobiological recovery post-stroke. The recovery of the ipsilesional extension of VSN was significantly slower for the total anterior circulation infarct (TACI) group compared to the non-TACI group. CONCLUSIONS: Larger strokes have a significant negative impact on recovery of visual attention at the non-hemiplegic side. No clinical determinants that regulate spontaneous time-dependent recovery of VSN were found. While early 'stroke severity' has been regarded as a strong predictor of functional outcome at a group level, other prognostic factors (demographic, stroke related) need to be determined. CLINICAL TRIAL REGISTRATION: EXPLICIT-stroke Trial: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1424 Stroke Intensity Trial: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1665.

Moving stroke rehabilitation forward: The need to change research.

BACKGROUND: Stroke rehabilitation aims to reduce impairments and promote activity and participation among patients. A major challenge for stroke rehabilitation research is to develop interventions that can reduce patients' neurological impairments. Until now, there has been no breakthrough in this research field. To move stroke rehabilitation forward, we need more knowledge about underlying mechanisms that drive spontaneous (i.e., reactive) neurobiological recovery after stroke and factors that can be used to optimize its prediction early after stroke onset. OBJECTIVE: The aim of the present invited review was therefore to elaborate on the time window of reactive neurobiological recovery, the proportional recovery rule and its generalizability to other neurological impairments, as well as to discuss the consequences for designing stroke recovery and rehabilitation trials. METHODS: In this narrative review, we offer suggestions to optimize the research designs of future stroke rehabilitation and recovery trials post stroke, in order to overcome the current prognostic heterogeneity introduced by variations in the potential for reactive neurobiological recovery. FINDINGS AND CONCLUSIONS: There is an urgent need for high-quality, explanatory trials in the first three months post stroke. These trials should preferably stratify patients based on their initial potential for reactive neurobiological recovery, measure recovery repeatedly at fixed times post stroke, and differentiate in their outcomes between behavioural restitution and compensation of functions.

Is the proportional recovery rule applicable to the lower limb after a first-ever ischemic stroke?

OBJECTIVE: To investigate (a) the applicability of the proportional recovery rule of spontaneous neurobiological recovery to motor function of the paretic lower extremity (LE); and (b) the presence of fitters and non-fitters of this prognostic rule poststroke. When present, the clinical threshold for fitting nor non-fitting would be determined, as well as within-subject generalizability to the paretic upper extremity (UE). METHODS: Prospective cohort study in which the Fugl-Meyer Assessment (FMA)-LE and FMA-UE were measured <72 hours and 6 months poststroke. Predicted maximum potential recovery was defined as [FMA-LEmax-FMA-LEinitial = 34 -FMA-LEinitial]. Hierarchical clustering in 202 first-ever ischemic stroke patients distinguished between fitting and not fitting the rule. Descriptive statistics determined whether fitters and non-fitters for LE were the same persons as for UE. RESULTS: 175 (87%) patients fitted the FMA-LE recovery rule. The observed average improvement of the fitters was ~64% of the predicted maximum potential recovery. In the non-fitter group, the maximum initial FMA-LE score was 13 points. Fifty-one out of 78 patients (~65%) who scored below the identified 14-point threshold at baseline fitted the FMA-LE rule. Non-fitters were more severely affected than fitters. All non-fitters of the FMA-LE rule did also not fit the proportional recovery rule for FMA-UE. CONCLUSIONS: Proportional recovery seems to be consistent within subjects across LE and UE motor impairment at the hemiplegic side in first-ever ischemic hemispheric stroke subjects. Future studies should investigate prospectively distinguishing between fitters and not-fitters within the subgroup of patients who have initial low FMA-LE scores. Subsequently, patients could be stratified based on fitting or not fitting the recovery rule as this would impact rehabilitation management and trial design.

No changes in functional connectivity during motor recovery beyond 5 weeks after stroke; A longitudinal resting-state fMRI study.

Spontaneous motor recovery after stroke appears to be associated with structural and functional changes in the motor network. The aim of the current study was to explore time-dependent changes in resting-state (rs) functional connectivity in motor-impaired stroke patients, using rs-functional MRI at 5 weeks and 26 weeks post-stroke onset. For this aim, 13 stroke patients from the EXPLICIT-stroke Trial and age and gender-matched healthy control subjects were included. Patients' synergistic motor control of the paretic upper-limb was assessed with the upper extremity section of the Fugl-Meyer Assessment (FMA-UE) within 2 weeks, and at 5 and 26 weeks post-stroke onset. Results showed that the ipsilesional rs-functional connectivity between motor areas was lower compared to the contralesional rs-functional connectivity, but this difference did not change significantly over time. No relations were observed between changes in rs-functional connectivity and upper-limb motor recovery, despite changes in upper-limb function as measured with the FMA-UE. Last, overall rs-functional connectivity was comparable for patients and healthy control subjects. To conclude, the current findings did not provide evidence that in moderately impaired stroke patients the lower rs-functional connectivity of the ipsilesional hemisphere changed over time.

Generalizability of the Maximum Proportional Recovery Rule to Visuospatial Neglect Early Poststroke.

BACKGROUND AND OBJECTIVE: Proportional recovery of upper-extremity motor function and aphasia after stroke may suggest common mechanisms for spontaneous neurobiological recovery. This study aimed to investigate if the proportional recovery rule also applies to visuospatial neglect (VSN) in right-hemispheric first-ever ischemic stroke patients and explored the possible common underlying mechanisms. METHODS: Patients with upper-limb paresis and VSN were included. Recovery defined as the change in Letter Cancellation Test (LCT) score at ~8 days and 6 months poststroke. Potential recovery defined as LCTmax-LCTinitial = 20 - LCTinitial. Hierarchical clustering separated fitters and nonfitters of the prediction rule. A cutoff value on LCTmax-LCTinitial was determined. The change in LCT and Fugl-Meyer Assessment Upper Extremity was expressed as a percentage of the total possible score to investigate the communality of proportional recovery. RESULTS: Out of 90 patients, 80 displayed proportional recovery of VSN (ie, "fitters," 0.97; 95% CI = 0.82-1.12). All patients who did not follow the prediction rule for VSN (ie, "nonfitters") had ≥15 missing O's at baseline and failed to show proportional recovery of the upper limb. CONCLUSIONS: This study shows that the proportional recovery rule also applies to patients with VSN poststroke. Patients who fail to show proportional recovery of VSN are the same patients who fail to show proportional recovery of the upper limb. These findings support the idea of common intrahemispheric mechanisms underlying spontaneous neurobiological recovery in the first months poststroke. Future studies should investigate the prognostic clinical and neurobiological markers of these subgroups.

How to design clinical rehabilitation trials for the upper paretic limb early post stroke?

BACKGROUND: The impact of spontaneous neurobiological recovery is still neglected in designing rehabilitation trials early post stroke. We aimed to investigate the impact of the timing of randomization and prognostic stratification on the required sample sizes that are needed to reveal significant intervention effects on upper limb function at 26 weeks after first-ever ischemic stroke. METHOD: Sample size calculations were based on a cohort study of 159 patients, using the Fugl-Meyer Assessment Upper Extremity and Action Research Arm Test as outcome measures (power = 80 %; two-tailed alpha = 0.05). We investigated different scenarios: random sampling of patients within five time intervals (stroke onset to 1, 3, 5, 8 and 12 weeks post stroke), and within stratified groups according to the presence or absence of voluntary extension of the thumb and/or two or more fingers at intake. RESULTS: The heterogeneity between outcome scores of patients, and subsequently the required sample sizes, increased from the first to the fifth time interval. Compared to the whole group, the sample sizes for both stratified groups (i.e., patients with and without Voluntary Finger Extension (VFE)) were lower. The required sample sizes for the patient group without VFE markedly increased when the time interval was broadened from 1 to 12 weeks post stroke, as opposed to the decrease seen for the group of patients with VFE. CONCLUSION: These results are fundamental for designing upper limb trials early post stroke. To prevent type II error, future upper limb trials should randomize patients at a fixed moment early post stroke and stratify patients according to their potential neurobiological recovery. TRIAL REGISTRATION: Netherlands Trial Registry, www.trialregister.nl , NTR1424 , registered on 27 August 2008.

When Does Return of Voluntary Finger Extension Occur Post-Stroke? A Prospective Cohort Study.

OBJECTIVES: Patients without voluntary finger extension early post-stroke are suggested to have a poor prognosis for regaining upper limb capacity at 6 months. Despite this poor prognosis, a number of patients do regain upper limb capacity. We aimed to determine the time window for return of voluntary finger extension during motor recovery and identify clinical characteristics of patients who, despite an initially poor prognosis, show upper limb capacity at 6 months post-stroke. METHODS: Survival analysis was used to assess the time window for return of voluntary finger extension (Fugl-Meyer Assessment hand sub item finger extension≥1). A cut-off of ≥10 points on the Action Research Arm Test was used to define return of some upper limb capacity (i.e. ability to pick up a small object). Probabilities for regaining upper limb capacity at 6 months post-stroke were determined with multivariable logistic regression analysis using patient characteristics. RESULTS: 45 of the 100 patients without voluntary finger extension at 8 ± 4 days post-stroke achieved an Action Research Arm Test score of ≥10 points at 6 months. The median time for regaining voluntary finger extension for these recoverers was 4 weeks (lower and upper percentile respectively 2 and 8 weeks). The median time to return of VFE was not reached for the whole group (N = 100). Patients who had moderate to good lower limb function (Motricity Index leg≥35 points), no visuospatial neglect (single-letter cancellation test asymmetry between the contralesional and ipsilesional sides of <2 omissions) and sufficient somatosensory function (Erasmus MC modified Nottingham Sensory Assessment≥33 points) had a 0.94 probability of regaining upper limb capacity at 6 months post-stroke. CONCLUSIONS: We recommend weekly monitoring of voluntary finger extension within the first 4 weeks post-stroke and preferably up to 8 weeks. Patients with paresis mainly restricted to the upper limb, no visuospatial neglect and sufficient somatosensory function are likely to show at least some return of upper limb capacity at 6 months post-stroke.

Effects of Unilateral Upper Limb Training in Two Distinct Prognostic Groups Early After Stroke: The EXPLICIT-Stroke Randomized Clinical Trial.

Background and Objective Favorable prognosis of the upper limb depends on preservation or return of voluntary finger extension (FE) early after stroke. The present study aimed to determine the effects of modified constraint-induced movement therapy (mCIMT) and electromyography-triggered neuromuscular stimulation (EMG-NMS) on upper limb capacity early poststroke. Methods A total of 159 ischemic stroke patients were included: 58 patients with a favorable prognosis (>10° of FE) were randomly allocated to 3 weeks of mCIMT or usual care only; 101 patients with an unfavorable prognosis were allocated to 3-week EMG-NMS or usual care only. Both interventions started within 14 days poststroke, lasted up until 5 weeks, focused at preservation or return of FE. Results Upper limb capacity was measured with the Action Research Arm Test (ARAT), assessed weekly within the first 5 weeks poststroke and at postassessments at 8, 12, and 26 weeks. Clinically relevant differences in ARAT in favor of mCIMT were found after 5, 8, and 12 weeks poststroke (respectively, 6, 7, and 7 points; P < .05), but not after 26 weeks. We did not find statistically significant differences between mCIMT and usual care on impairment measures, such as the Fugl-Meyer assessment of the arm (FMA-UE). EMG-NMS did not result in significant differences. Conclusions Three weeks of early mCIMT is superior to usual care in terms of regaining upper limb capacity in patients with a favorable prognosis; 3 weeks of EMG-NMS in patients with an unfavorable prognosis is not beneficial. Despite meaningful improvements in upper limb capacity, no evidence was found that the time-dependent neurological improvements early poststroke are significantly influenced by either mCIMT or EMG-NMS.

Generalizability of the Proportional Recovery Model for the Upper Extremity After an Ischemic Stroke.

BACKGROUND AND OBJECTIVE: Spontaneous neurological recovery after stroke is a poorly understood process. The aim of the present article was to test the proportional recovery model for the upper extremity poststroke and to identify clinical characteristics of patients who do not fit this model. METHODS: A change in the Fugl-Meyer Assessment Upper Extremity score (FMA-UE) measured within 72 hours and at 6 months poststroke served to define motor recovery. Recovery on FMA-UE was predicted using the proportional recovery model: ΔFMA-UEpredicted = 0.7·(66 - FMA-UEinitial) + 0.4. Hierarchical cluster analysis on 211 patients was used to separate nonfitters (outliers) from fitters, and differences between these groups were studied using clinical determinants measured within 72 hours poststroke. Subsequent logistic regression analysis served to predict patients who may not fit the model. RESULTS: The majority of patients (~70%; n = 146) showed a fixed proportional upper extremity motor recovery of about 78%; 65 patients had substantially less improvement than predicted. These nonfitters had more severe neurological impairments within 72 hours poststroke (P values <.01). Logistic regression analysis revealed that absence of finger extension, presence of facial palsy, more severe lower extremity paresis, and more severe type of stroke as defined by the Bamford classification were significant predictors of not fitting the proportional recovery model. CONCLUSIONS: These results confirm in an independent sample that stroke patients with mild to moderate initial impairments show an almost fixed proportional upper extremity motor recovery. Patients who will most likely not achieve the predicted amount of recovery were identified using clinical determinants measured within 72 hours poststroke.

Respiratory muscle power and the slow component of O2 uptake.

PURPOSE: The slow component of O2 uptake (V˙O2sc) represents a progressive decline in work efficiency during strenuous, constant work rate cycling. Although most of this "excess" O2 uptake can be explained by factors intrinsic to the exercising muscles, it has been proposed that respiratory muscle work rate may also contribute to the V˙O2sc response. To date, however, no study has provided a comprehensive analysis of the mechanical power of breathing (Pb) in relation to the V˙O2sc while performing strenuous exercise. METHODS: The mechanical Pb was measured in 12 recreational cyclists (24 ± 1 yr, 70.9 ± 3.9 kg) during heavy- and severe-intensity cycling. The resistive and elastic components of Pb were quantified using the modified Campbell diagram. RESULTS: Total Pb significantly increased (P < 0.05) over the V˙O2sc phase during both heavy (Δ13 ± 2 J·min) and severe work rate transitions (Δ219 ± 56 J·min). The magnitude of this increase was relatively greater during severe cycling trials (P < 0.05). The greater "slow component" rise in total Pb during severe work rate transitions was consequent to relatively larger increases in the inspiratory and expiratory resistive Pb and inspiratory elastic Pb (P < 0.05). CONCLUSIONS: The findings of this investigation support the thesis that the energetic contribution from respiratory muscles to the V˙O2sc amplitude is disproportionately higher during severe- compared with that during heavy-intensity exercise.