Early Subacute Stage Research Articles

High-intensity interval training is feasible, credible and clinically effective in the early subacute stroke stage in the low-income country of Benin

ABSTRACT High-intensity interval training (HIIT) has been shown to benefit stroke patients when implemented three months post-stroke. This study examined HIIT’s feasibility and clinical effectiveness in the early post-stroke stage in Benin. This was a prospective interventional study comprising an HIIT programme executed on a recumbent bike, three times/week, 20–30 min/session for 6 weeks, added to a conventional physiotherapy. The primary outcomes were feasibility, credibility and expectancy assessed with credibility and expectancy questionnaire. A maximal exercise test, 6-min walking test (6MWT), 10-m walking test (10mWT), Berg balance scale (BBS) and five repetitions sit-to-stand test (5 R-STS) were performed before and after the training programme. Ten outpatients, with a median age [P25-P75]: 63.5[56.7–71.2] years; time since stroke: 15.0[9.7–21.0] days, started and completed all training sessions without serious adverse events. High scores were observed on the Credibility subscale at admission (27.0[25.7–27.0]), which remained so after intervention (26.5[25.7–27.0]). Expectancy subscale scores were high at admission (25.5[24.0–27.0]) and post-training (25.5[24.5–27.0]). Peak workload (p < 0.001), BBS (p < 0.001), 6MWT (p < 0.001), 10mWT (p < 0.001) and 5 R-STS (p = 0.004) were all improved. HIIT is feasible and safe in the early subacute post-stroke stage and is perceived by patients as highly credible, meeting their expectations of recovery.

Smartphone-Based Speech Therapy for Poststroke Dysarthria: Pilot Randomized Controlled Trial Evaluating Efficacy and Feasibility.

Dysarthria is a common poststroke speech disorder affecting communication and psychological well-being. Traditional speech therapy is effective but often poses challenges in terms of accessibility and patient adherence. Emerging smartphone-based therapies may offer promising alternatives for the treatment of poststroke dysarthria. This study aimed to assess the efficacy and feasibility of smartphone-based speech therapy for improving speech intelligibility in patients with acute and early subacute poststroke dysarthria. This study also explored the impact of the intervention on psychological well-being, user experience, and overall feasibility in a clinical setting. Participants were divided into 2 groups for this randomized, evaluator-blinded trial. The intervention group used a smartphone-based speech therapy app for 1 hour per day, 5 days per week, for 4 weeks, with guideline-based standard stroke care. The control group received standard guideline-based stroke care and rehabilitation. Speech intelligibility, psychological well-being, quality of life, and user acceptance were assessed using repeated measures ANOVA. In this study, 40 patients with poststroke dysarthria were enrolled, 32 of whom completed the trial (16 in each group). The intervention group showed significant improvements in speech intelligibility compared with the control group. This was evidenced by improvements from baseline (F1,30=34.35; P<.001), between-group differences (F1,30=6.18; P=.02), and notable time-by-group interactions (F1,30=6.91; P=.01). Regarding secondary outcomes, the intervention led to improvements in the percentage of correct consonants over time (F1,30=5.57; P=.03). In addition, significant reductions were noted in the severity of dysarthria in the intervention group over time (F1,30=21.18; P<.001), with a pronounced group effect (F1,30=5.52; P=.03) and time-by-group interaction (F1,30=5.29; P=.03). Regarding quality of life, significant improvements were observed as measured by the EQ-5D-3L questionnaire (F1,30=13.25; P<.001) and EQ-VAS (F1,30=7.74; P=.009) over time. The adherence rate to the smartphone-based app was 64%, with over half of the participants completing all the sessions. The usability of the app was rated high (system usability score 80.78). In addition, the intervention group reported increased self-efficacy in using the app compared with the control group (F1,30=10.81; P=.003). The smartphone-based speech therapy app significantly improved speech intelligibility, articulation, and quality of life in patients with poststroke dysarthria. These findings indicate that smartphone-based speech therapy can be a useful assistant device in the management of poststroke dysarthria, particularly in the acute and early subacute stroke stages. ClinicalTrials.gov NCT05146765; https://clinicaltrials.gov/ct2/show/NCT05146765.

Stroke Recovery-Related Changes in Cortical Reactivity Based on Modulation of Intracortical Inhibition.

Cortical excitation/inhibition dynamics have been suggested as a key mechanism occurring after stroke. Their supportive or maladaptive role in the course of recovery is still not completely understood. Here, we used transcranial magnetic stimulation (TMS)-electroencephalography coupling to study cortical reactivity and intracortical GABAergic inhibition, as well as their relationship to residual motor function and recovery longitudinally in patients with stroke. Electroencephalography responses evoked by TMS applied to the ipsilesional motor cortex were acquired in patients with stroke with upper limb motor deficit in the acute (1 week), early (3 weeks), and late subacute (3 months) stages. Readouts of cortical reactivity, intracortical inhibition, and complexity of the evoked dynamics were drawn from TMS-evoked potentials induced by single-pulse and paired-pulse TMS (short-interval intracortical inhibition). Residual motor function was quantified through a detailed motor evaluation. From 76 patients enrolled, 66 were included (68.2±13.2 years old, 18 females), with a Fugl-Meyer score of the upper extremity of 46.8±19. The comparison with TMS-evoked potentials of healthy older revealed that most affected patients exhibited larger and simpler brain reactivity patterns (Pcluster<0.05). Bayesian ANCOVA statistical evidence for a link between abnormally high motor cortical excitability and impairment level. A decrease in excitability in the following months was significantly correlated with better motor recovery in the whole cohort and the subgroup of recovering patients. Investigation of the intracortical GABAergic inhibitory system revealed the presence of beneficial disinhibition in the acute stage, followed by a normalization of inhibitory activity. This was supported by significant correlations between motor scores and the contrast of local mean field power and readouts of signal dynamics. The present results revealed an abnormal motor cortical reactivity in patients with stroke, which was driven by perturbations and longitudinal changes within the intracortical inhibition system. They support the view that disinhibition in the ipsilesional motor cortex during the first-week poststroke is beneficial and promotes neuronal plasticity and recovery.

The volume and the distribution of premorbid white matter hyperintensities: Impact on post-stroke aphasia.

White matter hyperintensities (WMH) are a radiological manifestation of progressive white matter integrity loss. The total volume and distribution of WMH within the corpus callosum have been associated with pathological cognitive ageing processes but have not been considered in relation to post-stroke aphasia outcomes. We investigated the contribution of both the total volume of WMH, and the extent of WMH lesion load in the corpus callosum to the recovery of language after first-ever stroke. Behavioural and neuroimaging data from individuals (N = 37) with a left-hemisphere stroke were included at the early subacute stage of recovery. Spoken language comprehension and production abilities were assessed using word and sentence-level tasks. Neuroimaging data was used to derive stroke lesion variables (volume and lesion load to language critical regions) and WMH variables (WMH volume and lesion load to three callosal segments). WMH volume did not predict variance in language measures, when considered together with stroke lesion and demographic variables. However, WMH lesion load in the forceps minor segment of the corpus callosum explained variance in early subacute comprehension abilities (t = -2.59, p = .01) together with corrected stroke lesion volume and socio-demographic variables. Premorbid WMH lesions in the forceps minor were negatively associated with early subacute language comprehension after aphasic stroke. This negative impact of callosal WMH on language is consistent with converging evidence from pathological ageing suggesting that callosal WMH disrupt the neural networks supporting a range of cognitive functions.

Magnetic resonance imaging in assessing the staging of intracerebral hemorrhages in children

The purpose of the study was to evaluate the possibilities of MRI in determining the stage of hemorrhagic stroke (HS) depending on structural and perifocal changes in children.Materials and methods. The study included 46 patients (including 19 boys and 27 girls) aged from the 29th day of life to 18 years, with a clinical picture of cerebrovascular accident and the presence of HS in the brain substance (BS) during an MRI study. For statistical analysis, patients were divided into two groups: group 1 – patients examined in the first 48 hours from the onset of neurological symptoms (21 people), group 2 – after 48 hours (26 people). Comparison in two groups was carried out according to MR signs: the presence of perifocal cytotoxic edema, the presence of perifocal hemorrhagic impregnation, the presence of a cytoplasmic rim. Intergroup comparisons on a qualitative basis were carried out using Fisher's exact test.Results. As a result of the study, differential diagnostic criteria for the stages of HS in children were determined by analyzing the MRI semiotics of hematoma in combination with the symptom complex of perifocal changes (CPC) in the form of perifocal cytotoxic edema, perifocal hemorrhagic impregnation and cytoplasmic rim. Statistically significant differences in the frequency of occurrence of signs of perifocal cytotoxic edema and perifocal hemorrhagic impregnation in the groups were found. The presence of perifocal cytotoxic edema was statistically significant (p = 0.027) more common in group 1 (47% (n = 10), 95% CI 26–69) than in group 2 (16% (n = 4), 95% CI 5–36). The presence of perifocal hemorrhagic soaking was statistically significantly (p = 0.003) more common in group 1 (81% (n = 17), 95% CI 57–93) than in group 2 (36% (n = 9), 95% CI 18–57). In addition, a statistically significant (p = 0.005) difference was found in the incidence of CPC, which was observed in group 1 (28% (n = 6), CI 12–52) and was not observed in group 2 (0%, (n = 0), 95% CI 0–17).Conclusions. The use of T2, T1, FLAIR, SWI and DWI modes (b = 1000) in combination with ADC in the protocol of MRI examination of children is mandatory, and only a comparison of the characteristics of the MR signal from a hematoma in combination with an analysis of perifocal changes allows us to differentiate the stage of hemorrhage. HS in the acute and early subacute stages has a similar MRI semiotics, therefore, it is necessary to assess the complex of perifocal changes, which allows to differentiate these stages, as it is determined in patients examined in the first 48 hours (p &lt; 0.05) and is not observed after two days. SWI analysis makes it possible to differentiate the late subacute stage of hematoma from chronic due to different characteristics of the MR signal, and also allows you to establish the presence of perifocal hemorrhagic impregnation, which contributes to the differential diagnosis of hemorrhage in the early stages of the pathological process.

Identification of Differentially Expressed Proteins in Rats with Early Subacute Spinal Cord Injury using an iTRAQ-based Quantitative Analysis.

Injuries to the central nervous system (CNS), such as spinal cord injury (SCI), may devastate families and society. Subacute SCI may majorly impact secondary damage during the transitional period between the acute and subacute phases. A range of CNS illnesses has been linked to changes in the level of protein expression. However, the importance of proteins during the early subacute stage of SCI remains unknown. The role of proteins in the early subacute phase of SCI has not been established yet. SCI-induced damage in rats was studied using isobaric tagging for relative and absolute protein quantification (iTRAQ) to identify proteins that differed in expression 3 days after the injury, as well as proteins that did not alter in expression. Differentially expressed proteins (DEPs) were analyzed employing Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis to discover the biological processes, cell components, and molecular functions of the proteins. We also performed Gene Set Enrichment Analysis (GSEA) software BP pathway and KEGG analysis on all proteins to further identify their functions. In addition, the first 15 key nodes of a protein-protein interaction (PPI) system were found. During the early subacute stage of SCI, we identified 176 DEPs in total between the control and damage groups, with 114 (64.77%) being up-regulated and 62 (35.23%) being downregulated. As a result of this study, we discovered the most important cellular components and molecular activities, as well as biological processes and pathways, in the early subacute phase of SCI. The top 15 high-degree core nodes were Alb, Plg, F2, Serpina1, Fgg, Apoa1, Vim, Hpx, Apoe, Agt, Ambp, Pcna, Gc, F12, and Gfap. Our study could provide new views on regulating the pathogenesis of proteins in the early subacute phase after SCI, which provides a theoretical basis for exploring more effective therapeutic targets for SCI in the future.

Imaging findings of cerebral fat embolism

Cerebral fat embolism (CFE) is a rare complication of long bone or pelvic fractures. The diagnosis is difficult because of non-specific signs and symptoms occurring in conjunction with the features of traumatic injury, where imaging is often deferred in view of unstable vitals. We present two cases of CFE occurring post-internal fixation of femur fracture in young- and middle-aged adult males in early and late subacute stages, respectively; one patient had associated hypoxic-ischemic encephalopathy. It is important for radiologists to know the variable appearance on imaging to make a timely diagnosis.

Trunk Impairment Scale for Predicting Lumbar Spine Bone Mineral Density in Young Male Patients With Subacute Stroke

To investigate the relationship between Trunk Impairment Scale (TIS) and lumbar spine bone mineral density (BMD) in subacute stroke patients. Twenty-three subacute male stroke patients under the age of 65 were prospectively enrolled to exclude both postmenopausal and senile effects on BMD. The TIS, Berg Balance Scale, the Korean version of the Modified Barthel Index, and manual muscle test were measured at admission and 3 months after stroke onset. BMD of the bilateral lower extremities and lumbar vertebrae was measured by dual-energy X-ray absorptiometry 3 months after stroke onset. TIS at baseline (TIS_B) and TIS at 3 months after stroke (TIS_3m) showed significant correlations with lumbar BMD (TIS_B, r=0.522; TIS_3m, r=0.517). Through multiple regression analysis, the TIS_B was associated with lumbar BMD (adjusted R2=0.474). However, BMD of the bilateral lower extremities was not correlated with any clinical measurements except body mass index. We found a relationship between TIS_B and lumbar BMD in subacute young male stroke patients. Stroke patients with poor trunk control in the early subacute stage would have low BMD of vertebral bones at 3 months. The TIS can be useful for estimating bone fragility in the lumbar vertebrae of subacute stroke patients.

Early Subacute White Matter Hyperintensities and Recovery of Language After Stroke

Background White matter hyperintensities (WMH) are considered to contribute to diminished brain reserve, negatively impacting on stroke recovery. While WMH identified in the chronic phase after stroke have been associated with post-stroke aphasia, the contribution of premorbid WMH to the early recovery of language across production and comprehension has not been investigated. Objective To investigate the relationship between premorbid WMH severity and longitudinal comprehension and production outcomes in aphasia, after controlling for stroke lesion variables. Methods Longitudinal behavioral data from individuals with a left-hemisphere stroke were included at the early subacute (n = 37) and chronic (n = 28) stage. Spoken language comprehension and production abilities were assessed at both timepoints using word and sentence-level tasks. Magnetic resonance imaging (MRI) was performed at the early subacute stage to derive stroke lesion variables (volume and proportion damage to critical regions) and WMH severity rating. Results The presence of severe WMH explained an additional 18% and 25% variance in early subacute (t = −3.00, p = .004) and chronic (t = −3.60, P = .001) language comprehension abilities respectively, after controlling for stroke lesion variables. WMH did not predict additional variance of language production scores. Conclusions Subacute clinical MRI can be used to improve prognoses of recovery of aphasia after stroke. We demonstrate that severe early subacute WMH add to the prediction of impaired longitudinal language recovery in comprehension, but not production. This emphasizes the need to consider different domains of language when investigating novel neurobiological predictors of aphasia recovery.

Effective brain network analysis in unilateral and bilateral upper limb exercise training in subjects with stroke

Knowing the patterns of brain activation that occur and networks involved under different interventions is important for motor recovery in subjects with stroke. This study aimed to study the patterns of brain activation and networks in two interventions, affected upper limb side and bilateral exercise training, using concurrent functional near-infrared spectroscopy (fNIRS) imaging. Thirty-two patients in the early subacute stage were randomly divided into two groups: unilateral and bilateral groups. The patients in the unilateral group underwent isokinetic muscle strength training on the affected upper limb side and patients in the bilateral group underwent bilateral upper limb training. Oxyhemoglobin and deoxyhemoglobin concentration changes (ΔHbO2 and ΔHbR, respectively) were recorded in the ipsilateral and contralateral prefrontal cortex (IPFC and CPFC, respectively) and ipsilateral and contralateral motor cortex (IMC and CMC, respectively) by fNIRS equipment in the resting state and training conditions. The phase information of a 0.01-0.08Hz fNIRS signal was extracted by the wavelet transform method. Dynamic Bayesian inference was adopted to calculate the coupling strength and direction of effective connectivity. The network threshold was determined by surrogate signal method, the global (weighted clustering coefficient, global efficiency, and small-worldness) and local (degree, betweenness centrality, and local efficiency) network metrics were calculated. The degree of cerebral lateralization was also compared between the two groups. The results of covariance analysis showed that, compared with bilateral training, the coupling effect of CMC→IMC was significantly enhanced (p=0.03); also, the local efficiency of the IMC (p=0.01), IPFC (p<0.001), and CPFC (p=0.006) and the hemispheric autonomy index of IPFC (p=0.007) were significantly increased in unilateral training. In addition, there was a significant positive correlation between the coupling intensity of the inter-hemispheric motor area and the shifted local efficiency. The results indicated that unilateral upper limb training could more effectively promote the interaction and balance of bilateral motor hemispheres and help brain reorganization in the IMC and prefrontal cortex in stroke patients. The method provided in this study could be used to evaluate dynamic brain activation and network reorganization under different interventions, thus improving the strategy of rehabilitation intervention in a timely manner and resulting in better motor recovery.

Transcranial Direct Current Stimulation Enhances Neuroplasticity and Accelerates Motor Recovery in a Stroke Mouse Model.

More effective strategies are needed to promote poststroke functional recovery. Here, we evaluated the impact of bihemispheric transcranial direct current stimulation (tDCS) on forelimb motor function recovery and the underlying mechanisms in mice subjected to focal ischemia of the motor cortex. Photothrombotic stroke was induced in the forelimb brain motor area, and tDCS was applied once per day for 3 consecutive days, starting 72 hours after stroke. Grid-walking, single pellet reaching, and grip strength tests were conducted to assess motor function. Local field potentials were recorded to evaluate brain connectivity. Western immunoblotting, ELISA, quantitative real-time polymerase chain reaction, and Golgi-Cox staining were used to uncover tDCS-mediated stroke recovery mechanisms. Among our results, tDCS increased the rate of motor recovery, anticipating it at the early subacute stage. In this window, tDCS enhanced BDNF (brain-derived neurotrophic factor) expression and dendritic spine density in the peri-infarct motor cortex, along with increasing functional connectivity between motor and somatosensory cortices. Treatment with the BDNF TrkB (tropomyosin-related tyrosine kinase B) receptor inhibitor, ANA-12, prevented tDCS effects on motor recovery and connectivity as well as the increase of spine density, pERK (phosphorylated extracellular signal-regulated kinase), pCaMKII (phosphorylated calcium/calmodulin-dependent protein kinase II), pMEF (phosphorylated myocyte-enhancer factor), and PSD (postsynaptic density)-95. The tDCS-promoted rescue was paralleled by enhanced plasma BDNF level, suggesting its potential role as circulating prognostic biomarker. The rate of motor recovery is accelerated by tDCS applied in the subacute phase of stroke. Anticipation of motor recovery via vicariate pathways or neural reserve recruitment would potentially enhance the efficacy of standard treatments, such as physical therapy, which is often delayed to a later stage when plastic responses are progressively lower.

Longitudinal Study of Optic Disk Perfusion and Retinal Structure in Leber's Hereditary Optic Neuropathy.

PurposeThe purpose of this study was to evaluate optic disk perfusion and neural retinal structure in patients with subacute Leber's hereditary optic neuropathy (LHON) and LHON carriers, as compared with healthy controls.MethodsThis study included 8 patients with LHON in the subacute stage, 10 asymptomatic carriers of a LHON-associated mitochondrial DNA mutation, and 40 controls. All subjects underwent measurement of the retinal nerve fiber layer (RNFL) thickness, the ganglion cell-inner plexiform layer (GCIPL) thickness using optical coherence tomography and optic disk microvascular perfusion (Mean Tissue [MT]) using laser speckle flowgraphy (LSFG). Patients were re-examined after a median interval of 3 months from the baseline visit.ResultsLHON carriers had higher values of RNFL thickness, GCIPL thickness, and disk area than controls (P < 0.05), whereas MT was not different between the two groups (P = 0.936). Median MT and RNFL thickness were 32% and 15% higher in the early subacute stage of the disease than in controls (P < 0.001 and P = 0.001). MT declined below the values of controls during the late subacute stage (P = 0.024), whereas RNFL thickness declined later during the dynamic stage (P < 0.001). GCIPL thickness was lower in patients with LHON than in controls independently of the stage of the disease (P < 0.001).ConclusionsThe high blood flow at the optic disk during the early subacute stage may be the consequence of vasodilation due to nitric oxide release as compensation to mitochondrial impairment. Optic disk perfusion as measured by LSFG is a promising biomarker for LHON diagnosis and monitoring as well as an objective outcome measure for assessing response to therapies.

EEG Fractal Analysis Reflects Brain Impairment after Stroke.

Stroke is the commonest cause of disability. Novel treatments require an improved understanding of the underlying mechanisms of recovery. Fractal approaches have demonstrated that a single metric can describe the complexity of seemingly random fluctuations of physiological signals. We hypothesize that fractal algorithms applied to electroencephalographic (EEG) signals may track brain impairment after stroke. Sixteen stroke survivors were studied in the hyperacute (<48 h) and in the acute phase (∼1 week after stroke), and 35 stroke survivors during the early subacute phase (from 8 days to 32 days and after ∼2 months after stroke): We compared resting-state EEG fractal changes using fractal measures (i.e., Higuchi Index, Tortuosity) with 11 healthy controls. Both Higuchi index and Tortuosity values were significantly lower after a stroke throughout the acute and early subacute stage compared to healthy subjects, reflecting a brain activity which is significantly less complex. These indices may be promising metrics to track behavioral changes in the very early stage after stroke. Our findings might contribute to the neurorehabilitation quest in identifying reliable biomarkers for a better tailoring of rehabilitation pathways.

Translational Value of Skilled Reaching Assessment in Clinical and Preclinical Studies on Motor Recovery After Stroke

Background Assessment of skilled reaching enables extensive analysis of upper limb function in clinical and preclinical studies on poststroke outcome. However, translational research if often limited by lack of correspondence between tests of human and rodent motor function. Objectives To determine (1) the translational value of skilled reaching performance for preclinical research by comparing the behavioral recovery profiles of skilled reaching characteristics between humans and rats recovering from stroke and (2) the relationship between skilled reaching performance and commonly used clinical outcome measures after stroke. Methods Twelve patients with ischemic or hemorrhagic stroke and 17 rats with photothrombotic stroke underwent an equivalent skilled reaching test at different time points, representing early to late subacute stages poststroke. Success scores and a movement element rating scale were used to measure the skilled reaching performance. The Fugl-Meyer Upper Extremity (FM-UE) assessment and the Action Research Arm Test (ARAT) were used as clinical outcome measures. Results Both species had muscle flaccidity at the early subacute stage after stroke and showed motor recovery following a proximal-distal principle toward the early subacute stage, albeit for rats within a shorter time course. Human skilled reaching scores and FM-UE and ARAT scores in the first 3 months poststroke were significantly correlated (P < .05). Conclusions Our study demonstrates that poststroke changes in skilled reaching performance are highly similar between rats and humans and correspond with standard clinical outcome measures. Skilled reaching testing therefore offers an effective and highly translational means for assessment of motor recovery in experimental and clinical stroke settings.

Initial Experience of Challenge-Free MRI-Based Oxygen Extraction Fraction Mapping of Ischemic Stroke at Various Stages: Comparison With Perfusion and Diffusion Mapping.

MRI-based oxygen extraction fraction imaging has a great potential benefit in the selection of clinical strategies for ischemic stroke patients. This study aimed to evaluate the performance of a challenge-free oxygen extraction fraction (OEF) mapping in a cohort of acute and subacute ischemic stroke patients. Consecutive ischemic stroke patients (a total of 30 with 5 in the acute stage, 19 in the early subacute stage, and 6 in the late subacute stage) were recruited. All subjects underwent MRI including multi-echo gradient echo (mGRE), diffusion weighted imaging (DWI), and 3D-arterial spin labeling (ASL). OEF maps were generated from mGRE phase + magnitude data, which were processed using quantitative susceptibility mapping (QSM) + quantitative blood oxygen level-dependent (qBOLD) imaging with cluster analysis of time evolution. Cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) maps were reconstructed from 3D-ASL and DWI, respectively. Further, cerebral metabolic rate of oxygen (CMRO2) was calculated as the product of CBF and OEF. OEF, CMRO2, CBF, and ADC values in the ischemic cores (absolute values) and their contrasts to the contralateral regions (relative values) were evaluated. One-way analysis of variance (ANOVA) was used to compare OEF, CMRO2, CBF, and ADC values and their relative values among different stroke stages. The OEF value of infarct core showed a trend of decrease from acute, to early subacute, and to late subacute stages of ischemic stroke. Significant differences among the three stroke stages were only observed in the absolute OEF (F = 6.046, p = 0.005) and relative OEF (F = 5.699, p = 0.009) values of the ischemic core, but not in other measurements (absolute and relative CMRO2, CBF, ADC values, all values of p > 0.05). In conclusion, the challenge-free QSM + qBOLD-generated OEF mapping can be performed on stroke patients. It can provide more information on tissue viability that was not available with CBF and ADC and, thus, may help to better manage ischemic stroke patients.

Effect of Transcranial Low-Level Light Therapy vs Sham Therapy Among Patients With Moderate Traumatic Brain Injury

Preclinical studies have shown that transcranial near-infrared low-level light therapy (LLLT) administered after traumatic brain injury (TBI) confers a neuroprotective response. To assess the feasibility and safety of LLLT administered acutely after a moderate TBI and the neuroreactivity to LLLT through quantitative magnetic resonance imaging metrics and neurocognitive assessment. A randomized, single-center, prospective, double-blind, placebo-controlled parallel-group trial was conducted from November 27, 2015, through July 11, 2019. Participants included 68 men and women with acute, nonpenetrating, moderate TBI who were randomized to LLLT or sham treatment. Analysis of the response-evaluable population was conducted. Transcranial LLLT was administered using a custom-built helmet starting within 72 hours after the trauma. Magnetic resonance imaging was performed in the acute (within 72 hours), early subacute (2-3 weeks), and late subacute (approximately 3 months) stages of recovery. Clinical assessments were performed concomitantly and at 6 months via the Rivermead Post-Concussion Questionnaire (RPQ), a 16-item questionnaire with each item assessed on a 5-point scale ranging from 0 (no problem) to 4 (severe problem). The number of participants to successfully and safely complete LLLT without any adverse events within the first 7 days after the therapy was the primary outcome measure. Secondary outcomes were the differential effect of LLLT on MR brain diffusion parameters and RPQ scores compared with the sham group. Of the 68 patients who were randomized (33 to LLLT and 35 to sham therapy), 28 completed at least 1 LLLT session. No adverse events referable to LLLT were reported. Forty-three patients (22 men [51.2%]; mean [SD] age, 50.49 [17.44] years]) completed the study with at least 1 magnetic resonance imaging scan: 19 individuals in the LLLT group and 24 in the sham treatment group. Radial diffusivity (RD), mean diffusivity (MD), and fractional anisotropy (FA) showed significant time and treatment interaction at 3-month time point (RD: 0.013; 95% CI, 0.006 to 0.019; P < .001; MD: 0.008; 95% CI, 0.001 to 0.015; P = .03; FA: -0.018; 95% CI, -0.026 to -0.010; P < .001).The LLLT group had lower RPQ scores, but this effect did not reach statistical significance (time effect P = .39, treatment effect P = .61, and time × treatment effect P = .91). In this randomized clinical trial, LLLT was feasible in all patients and did not exhibit any adverse events. Light therapy altered multiple diffusion tensor parameters in a statistically significant manner in the late subacute stage. This study provides the first human evidence to date that light therapy engages neural substrates that play a role in the pathophysiologic factors of moderate TBI and also suggests diffusion imaging as the biomarker of therapeutic response. ClinicalTrials.gov Identifier: NCT02233413.

Clinical and neuroimaging factors associated with aphasia severity in stroke patients: diffusion tensor imaging study

This study investigated factors associated with aphasia severity at both 2 weeks and 3 months after stroke using demographic and clinical variables, brain diffusion tensor imaging (DTI) parameters, and lesion volume measurements. Patients with left hemisphere stroke were assessed at 2 weeks (n = 68) and at 3 months (n = 20) after stroke. Demographic, clinical, and neuroimaging data were collected; language functions were assessed using the Western Aphasia Battery. For neuroimaging, DTI parameters, including the laterality index (LI) of fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity, mean diffusivity and fibre density (FD) of the arcuate fasciculus (AF), and lesion volume, were measured. Lesion volume, cortical involvement, and the National Institutes of Health Stroke Scale score significantly predicted aphasia severity at 2 weeks after stroke, whereas the aphasia quotient and presence of depression during the early subacute stage were significant predictors at 3 months after stroke. According to Pearson correlation, LI-AD and LI-FD were significantly correlated with the aphasia quotient 2 weeks after ischaemic stroke, and the LI-FA was significantly correlated with the aphasia quotient 2 weeks after haemorrhagic stroke, suggesting that the extent and mechanism of AF injuries differ between ischaemic and haemorrhagic strokes. These differences may contribute to aphasia severity.

Importance of Chronological Changes on High-Resolution Vessel Wall Imaging for Diagnosis of Isolated Anterior Cerebral Artery Dissection

IntroductionThe accurate diagnosis of isolated anterior cerebral artery dissection (iACA-D) is made difficult by the spatial resolution on conventional magnetic resonance imaging (MRI) techniques including time-of-flight magnetic resonance angiography that is too limited to detect minute arterial wall abnormalities. Recent advances in high-resolution vessel wall imaging (HRVWI), which can detect intramural hematomas (IMH), have improved the noninvasive diagnostic accuracy of iACA-D. However, despite the risk of overlooking minute IMH and aneurysmal dilations especially at the early disease stage, the utility of T1-weighted and T2-weighted HRVWI at each disease stage (i.e., acute, early subacute, late subacute and chronic) has not been evaluated thoroughly enough. This prompted us to undertake the present study to determine the diagnostic value of chronological changes of IMHs on T1-weighted HRVWI and arterial dilations on T2-weighted HRVWI to achieve the earliest possible and most accurate diagnosis of iACA-D. MethodsIn addition to six patients with iACA-D, five previously reported iACA-D patients from three institutions for whom reliable information on HRVWI and its examination date was available were enrolled in this study. IMHs on T1-weighted HRVWI and aneurysmal dilations on T2-weighted HRVWI and their chronological changes were visually evaluated. ResultsEither or both of IMHs on T1-weighted HRVWI and aneurysmal dilations on T2-weighted HRVWI were detected in all our six patients and the five previously reported ones. The disease stage showed a notable influence on the degree of their visualization. In contrast to IMHs which are regarded as the gold standard for the diagnosis of intracranial dissections, aneurysmal dilations were identified in 80% of cases even at the acute stage, reaching 100% at the early subacute stage. Despite the excellent detection rate of IMHs at the late subacute stage (100%), their detectability is poor at the acute and early subacute stages (0 and 40%, respectively). ConclusionThe results of this study highlighted the importance of aneurysmal dilations on T2-weighted HRVWI as a diagnostic marker to raise suspicion of iACA-D at the acute and early subacute stages, and similarly IMHs on T1-weighted HRVWI to confirm the diagnosis of iACA-D at the late subacute stage. These stage-dependent detectability changes in IMHs and aneurysmal dilations make an understanding of the chronological changes of these abnormal imaging findings mandatory to achieve an early and accurate diagnosis of iACA-D.

Sixto Obrador SENEC prize 2019: Utility of diffusion tensor imaging as a prognostic tool in moderate to severe traumatic brain injury. Part I. Analysis of DTI metrics performed during the early subacute stage

Background and objectivesTraumatic axonal injury (TAI) contributes significantly to mortality and morbidity after traumatic brain injury (TBI). Its identification is still a diagnostic challenge because of the limitations of conventional imaging techniques to characterized it. Diffusion tensor imaging (DTI) can indirectly identify areas of damaged white matter (WM) integrity by detecting water molecule diffusion alterations. Our main objective is to characterize the TAI using DTI at the early subacute stage in our series of moderate to severe TBI patients and to evaluate if there is a relationship between the information provided by the DTI and patient’s outcome. Materials and methodsWe have obtained DTI data from 217 patients with moderate to severe TBI acquired at a median of 19 days after TBI, and patient DTI metrics were compared with data obtained from 58 age-matched healthy controls. Region of interest (ROI) method was applied to obtain mean fractional anisotropy (FA) value in 28 WM fiber bundles susceptible to TAI. ResultsOur main results were that when we compared patients with controls, patients, regardless of TBI severity, showed significantly reduced mean FA in almost all ROI measured. We found statistically significant correlation between FA metrics and some clinical characteristics. Additionally, the FA values of the three portions of Corpus callosum, Cingulum and cerebral peduncles measured at the early subacute stage were highly associated with outcome assessed at hospital discharge and at 6 and 12 months after TBI. ConclusionsWe conclude that DTI is a useful tool to characterize TAI and the detection of FA reduction in the subacute stage after TBI is associated with long-term unfavorable outcome.

Utility of T2-weighted high-resolution vessel wall imaging for the diagnosis of isolated posterior inferior cerebellar artery dissection at acute and early subacute stages

Recent advances in magnetic resonance high-resolution vessel wall imaging (HRVWI), which can detect intramural hematomas (IMH), improve the noninvasive diagnostic accuracy of isolated posterior inferior cerebellar artery dissection (iPICA-D). However, despite the risk of overlooking minute IMH, the utility of T2-weighted HRVWI has not been thoroughly evaluated. This study aimed to compare the utility of T2-weighted HRVWI with that of T1-weighted HRVWI, basiparallel anatomical scanning (BPAS), and magnetic resonance angiography (MRA) for the diagnosis of iPICA-D mainly in the acute and early subacute stages in 6 iPICA-D patients (three acute, two early subacute and one late subacute stages on initial examinations). Dissection-related abnormalities included IMH on T1-weighted HRVWI, aneurysmal dilations on T2-weighted HRVWI and discrepancy between BPAS and MRA. On initial examinations, T2-weighted HRVWI revealed iPICA-D-related abnormalities more conspicuously than did T1-weighted HRVWI and combination of BPAS and MRA. Except in a single case with a discrepancy between the outer contour on BPAS and inner contour on MRA, no specific abnormalities were detected besides T2-weighted HRVWI at acute or early subacute stages. In addition to T1-weighted HRVWI, BPAS and MRA, T2-weighted HRVWI should be performed to diagnose acute and early subacute iPICA-D.