Correlates of Post-Stroke Brain Plasticity, Relationship to Pathophysiological Settings and Implications for Human Proof-of-Concept Studies

Stroke is the leading cause of adult disability in the USA and aphasia is a common consequence of dominant-hemispheric strokes. It is unclear why some recover with speech therapy, while others persist with debilitating deficits. One theory suggests that therapy-related brain plasticity provides the anatomical substrate for improvements in language. In this longitudinal study, we assessed the integrity of the ipsi- and contralateral inferior longitudinal fasciculus (ILF) using diffusional kurtosis MRI (DKI), and examined its relationship with aphasia-therapy related changes in semantic errors. 8 subjects (age = 52.0±7.2y; 62% male; MRI time post-stroke = 50.25±29.8m) with chronic post-stroke aphasia received Language Action Therapy for a period of 3 weeks. Structural images (T1 & T2) and DKI (30 directions, b= [1000, 2000 s/mm 2 ]) were acquired. We applied an innovative form of tractography using Diffusion Kurtosis Estimator and a WM mask as a seeding region. Lastly, we optimized the automated fiber quantification software to acquire along-tract diffusion measurements resulting in 100 nodal mean kurtosis (MK), mean diffusivity (MD) and fractional anisotropy (FA) measurements along major tracts. Compared to the contralateral side, the ipsilateral ILF shows diffusion characteristics often found in damaged neuronal tissue: high MD, low FA, and low MK (figure1). The variability is larger on the ipsilateral side, and lowest MK correlated significantly with an increase in semantic errors (r=-0.84, p<0.05). None of the associations with FA and MD reached significance. Additionally, a therapy related reduction in semantic errors was associated with a longitudinal increase in MK (r=-0.89, p<0.05). In conclusion, ILF integrity captured using MK relates to clinical performance with lower MK predicting worse semantic language production, whereas therapy related increases in microstructural complexity (higher MK) were associated with a decrease in semantic errors.

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Tele-rehabilitation of upper-extremity hemiparesis after stroke: Proof-of-concept randomized controlled trial of in-home constraint-induced movement therapy

Restorative Neurology and Neuroscience ◽

10.3233/rnn-201100 ◽

2021 ◽

pp. 1-16

Author(s):

Gitendra Uswatte ◽

Edward Taub ◽

Peter Lum ◽

David Brennan ◽

Joydip Barman ◽

...

Keyword(s):

Upper Extremity ◽

Controlled Trial ◽

Movement Therapy ◽

Proof Of Concept ◽

Upper Arm ◽

Long Term Outcome ◽

Post Stroke ◽

Constraint Induced Movement Therapy ◽

Health Group ◽

One Year

Background: Although Constraint-Induced Movement therapy (CIMT) has been deemed efficacious for adults with persistent, mild-to-moderate, post-stroke upper-extremity hemiparesis, CIMT is not available on a widespread clinical basis. Impediments include its cost and travel to multiple therapy appointments. To overcome these barriers, we developed an automated, tele-health form of CIMT. Objective: Determine whether in-home, tele-health CIMT has outcomes as good as in-clinic, face-to-face CIMT in adults ≥1-year post-stroke with mild-to-moderate upper-extremity hemiparesis. Methods: Twenty-four stroke patients with chronic upper-arm extremity hemiparesis were randomly assigned to tele-health CIMT (Tele-AutoCITE) or in-lab CIMT. All received 35 hours of treatment. In the tele-health group, an automated, upper-extremity workstation with built-in sensors and video cameras was set-up in participants’ homes. Internet-based audio-visual and data links permitted supervision of treatment by a trainer in the lab. Results: Ten patients in each group completed treatment. All twenty, on average, showed very large improvements immediately afterwards in everyday use of the more-affected arm (mean change on Motor Activity Log Arm Use scale = 2.5 points, p < 0.001, d’ = 3.1). After one-year, a large improvement from baseline was still present (mean change = 1.8, p < 0.001, d’ = 2). Post-treatment outcomes in the tele-health group were not inferior to those in the in-lab group. Neither were participants’ perceptions of satisfaction with and difficulty of the interventions. Although everyday arm use was similar in the two groups after one-year (mean difference = –0.1, 95%CI = –1.3–1.0), reductions in the precision of the estimates of this parameter due to drop-out over follow-up did not permit ruling out that the tele-health group had an inferior long-term outcome. Conclusions: This proof-of-concept study suggests that Tele-AutoCITE produces immediate benefits that are equivalent to those after in-lab CIMT in stroke survivors with chronic upper-arm extremity hemiparesis. Cost savings possible with this tele-health approach remain to be evaluated.

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Brain plasticity and recovery of auditory comprehension in chronic post-stroke aphasia

Journal of the Neurological Sciences ◽

10.1016/j.jns.2015.08.1259 ◽

2015 ◽

Vol 357 ◽

pp. e353

Author(s):

J. Hurtado ◽

L. Núñez

Keyword(s):

Brain Plasticity ◽

Auditory Comprehension ◽

Post Stroke

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Abstract T MP46: Stroke-Related Neuroplasticity During Steering of Human Gait

Stroke ◽

10.1161/str.45.suppl_1.tmp46 ◽

2014 ◽

Vol 45 (suppl_1) ◽

Author(s):

Caroline Paquette ◽

Jean-Paul Soucy

Keyword(s):

Brain Plasticity ◽

Brain Activity ◽

Brain Regions ◽

Whole Body ◽

Human Gait ◽

Stroke Survivors ◽

Post Stroke ◽

Positron Emission ◽

18F Fdg

Background: The risk of falling is higher in stroke survivors than among the general population. These falls are more frequent during walking and transfers or during turning. The neuronal substrates involved in steering of locomotion are poorly understood due to methodological limitations in quantifying brain activations during whole-body movements. Thus, no data is currently available to study the mechanisms of post-stroke brain plasticity for steering of gait. This study tested the hypothesis that stroke-induced neuroplastic changes for steering of gait can be quantified using 18F- fluorodesoxy-glucose (18F-FDG) Positron Emission Tomography (PET) in-vivo in humans Methods: PET imaging with 18F-FDG tracer was used to quantify cerebral glucose metabolism (CMRGlc) during two locomotor tasks (straight walking and turning) measured on separate days. Immediately prior to each walking task, a 5 mCi bolus of 18F-FDG was injected. Subjects walked for 40 minutes (duration of 18F-FDG uptake). Subjects were scanned on an ECAT HR+ scan (20min emission followed by 10min transmission) within 10 minutes of completing the walking task, well within reaching the 2h half-life of 18F. Images obtained during straight walking were subtracted from the ones acquired during steering Results: Subjects post-stroke showed an asymmetrical pattern of CMRGlc in sensorimotor areas and superior parietal lobule where the affected hemisphere shows no increase in CMRGlc. Differences between groups were also observed in the cerebellum where CMRGlc was increased in the vermis for controls, an area predominant for the control of trunk and gait. Stroke subjects, in contrast, showed increased CMRGlc in the hemishperes, associated with goal-directed leg movements. Conclusions: Neuroplasticity in complex locomotor tasks such as steering can be quantified using 18F-FDG PET in subjects post-stroke. This study showed that changes affect several brain regions remote to the infarct. Understanding stroke-related changes in brain activity during steering of locomotion is crucial for improving rehabilitative strategies to minimize falls and injuries in stroke survivors.

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Stochastic Resonance Stimulation in Brain Plasticity and Post Stroke Motor Recovery

Case Medical Research ◽

10.31525/ct1-nct03839810 ◽

2000 ◽

Author(s):

Keyword(s):

Stochastic Resonance ◽

Brain Plasticity ◽

Motor Recovery ◽

Post Stroke

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Intravenous lacosamide as treatment option in post-stroke non convulsive status epilepticus in the elderly: A proof-of-concept, observational study

Seizure ◽

10.1016/j.seizure.2013.07.011 ◽

2013 ◽

Vol 22 (10) ◽

pp. 905-907 ◽

Cited By ~ 25

Author(s):

Vincenzo Belcastro ◽

Simone Vidale ◽

Laura Pierguidi ◽

Luigi Sironi ◽

Lucia Tancredi ◽

...

Keyword(s):

Status Epilepticus ◽

Observational Study ◽

Treatment Option ◽

The Elderly ◽

Convulsive Status Epilepticus ◽

Proof Of Concept ◽

Post Stroke

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Augmented-reality guided treadmill training as a modality to improve functional mobility post-stroke: A proof-of-concept case series

Topics in Stroke Rehabilitation ◽

10.1080/10749357.2020.1864987 ◽

2020 ◽

pp. 1-7

Author(s):

Nabela Enam ◽

Akhila Veerubhotla ◽

Naphtaly Ehrenberg ◽

Steven Kirshblum ◽

Karen J. Nolan ◽

...

Keyword(s):

Augmented Reality ◽

Case Series ◽

Functional Mobility ◽

Treadmill Training ◽

Proof Of Concept ◽

Post Stroke

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New Insights Into the Roles of Microglial Regulation in Brain Plasticity-Dependent Stroke Recovery

Frontiers in Cellular Neuroscience ◽

10.3389/fncel.2021.727899 ◽

2021 ◽

Vol 15 ◽

Author(s):

Fang Yu ◽

Tingting Huang ◽

Yuanyuan Ran ◽

Da Li ◽

Lin Ye ◽

...

Keyword(s):

Microglial Activation ◽

Brain Injuries ◽

Inflammatory Responses ◽

Brain Plasticity ◽

Functional Restoration ◽

Stroke Recovery ◽

Special Focus ◽

Post Stroke ◽

Functional Connections

Stroke remains the leading cause of long-term disability worldwide with significant long-term sequelae. However, there is no highly effective treatment to enhance post-stroke recovery despite extensive efforts in exploring rehabilitative therapies. Neurorehabilitation is recognized as the cornerstone of functional restoration therapy in stroke, where treatments are focused on neuroplastic regulation to reverse neural structural disruption and improve neurofunctional networks. Post-stroke neuroplasticity changes begin within hours of symptom onset and reaches a plateau by 3 to 4 weeks within the global brain in animal studies. It plays a determining role in spontaneous stroke recovery. Microglia are immediately activated following cerebral ischemia, which has been found both proximal to the primary ischemic injury and at the remote brain regions which have functional connections to the primary injury area. Microglia exhibit different activation profiles based on the microenvironment and adaptively switch their phenotypes in a spatiotemporal manner in response to brain injuries. Microglial activation coincides with neuroplasticity after stroke, which provides the fundamental base for the microglia-mediated inflammatory responses involved in the entire neural network rewiring and brain repair. Microglial activation exerts important effects on spontaneous recovery after stroke, including structural and functional reestablishment of neurovascular networks, neurogenesis, axonal remodeling, and blood vessel regeneration. In this review, we focus on the crosstalk between microglial activation and endogenous neuroplasticity, with a special focus on the plastic alterations in the whole brain network and their implications for structural and functional restoration after stroke. We then summarize recent advances in the impacts of microglial phenotype polarization on brain plasticity, trying to discuss the potential efficacy of microglia-based extrinsic restorative interventions in promoting post-stroke recovery.

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Effect of Rehabilitation with Extremely Low Frequency Electromagnetic Field on Molecular Mechanism of Apoptosis in Post-Stroke Patients

Brain Sciences ◽

10.3390/brainsci10050266 ◽

2020 ◽

Vol 10 (5) ◽

pp. 266 ◽

Cited By ~ 2

Author(s):

Natalia Cichon ◽

Ewelina Synowiec ◽

Elzbieta Miller ◽

Tomasz Sliwinski ◽

Michal Ceremuga ◽

...

Keyword(s):

Electromagnetic Field ◽

Mrna Expression ◽

Molecular Mechanism ◽

Brain Plasticity ◽

Low Frequency ◽

Rehabilitation Program ◽

Stroke Severity ◽

Stroke Patients ◽

Extremely Low Frequency ◽

Post Stroke

Apoptosis in acute stroke is associated with a negative prognosis and is correlated with the severity of the neurological deficit. However, there is no evidence that indicates that, in the subacute phase of the stroke, the apoptosis process might activate neuroplasticity. Therefore, in this study, we investigated the effect of an extremely low frequency electromagnetic field (ELF-EMF) on the molecular mechanism of apoptosis, as used in the rehabilitation of post-stroke patients. Patients with moderate stroke severity (n = 48), 3–4 weeks after incident, were enrolled in the analysis and divided into ELF-EMF and non-ELF-EMF group. The rehabilitation program in both groups involves the following: kinesiotherapy—30 min; psychological therapy—15 min; and neurophysiological routines—60 min. Additionally, the ELF-EMF group was exposed to an ELF-EMF (40 Hz, 5 mT). In order to assess the apoptosis gene expression level, we measured the mRNA expression of BAX, BCL-2, CASP8, TNFα, and TP53. We found that ELF-EMF significantly increased the expression of BAX, CASP8, TNFα, and TP53, whereas the BCL-2 mRNA expression after ELF-EMF exposition remained at a comparable level in both groups. Thus, we suggest that increasing the expression of pro-apoptotic genes in post-stroke patients promotes the activation of signaling pathways involved in brain plasticity processes. However, further research is needed to clarify this process.

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