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The Strength of the Corticospinal Tract Not the Reticulospinal Tract Determines Upper-Limb Impairment Level and Capacity for Skill-Acquisition in the Sub-Acute Post-Stroke Period.

ABSTRACT: Background. Upper-limb impairment in patients with chronic stroke appears to be partly attributable to an upregulated reticulospinal tract (RST). Here, we assessed whether the impact of corticospinal (CST) and RST connectivity on motor impairment and skill-acquisition differs in sub-acute stroke, using transcranial magnetic stimulation (TMS)-based proxy measures. Methods. Thirty-eight stroke survivors were randomized to either reach training 3-6 weeks post-stroke (plus usual care) or usual care only. At 3, 6 and 12 weeks post-stroke, we measured ipsilesional and contralesional cortical connectivity (surrogates for CST and RST connectivity, respectively) to weak pre-activated triceps and deltoid muscles with single pulse TMS, accuracy of planar reaching movements, muscle strength (Motricity Index) and synergies (Fugl-Meyer upper-limb score). Results. Strength and presence of synergies were associated with ipsilesional (CST) connectivity to the paretic upper-limb at 3 and 12 weeks. Training led to planar reaching skill beyond that expected from spontaneous recovery and occurred for both weak and strong ipsilesional tract integrity. Reaching ability, presence of synergies, skill-acquisition and strength were not affected by either the presence or absence of contralesional (RST) connectivity. Conclusion. The degree of ipsilesional CST connectivity is the main determinant of proximal dexterity, upper-limb strength and synergy expression in sub-acute stroke. In contrast, there is no evidence for enhanced contralesional RST connectivity contributing to any of these components of impairment. In the sub-acute post-stroke period, the balance of activity between CST and RST may matter more for the paretic phenotype than RST upregulation per se.

SUBMITTER: Hammerbeck U

PROVIDER: S-EPMC8414832 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Brain lesion characteristics (timing, location, and extent) and the type of corticospinal tract (CST) wiring have been proposed as determinants of upper limb (UL) motor function in unilateral cerebral palsy (uCP), yet an investigation of the relative combined impact of these factors on both motor and sensory functions is still lacking. Here, we first investigated whether structural brain lesion characteristics could predict the underlying CST wiring and we explored the role of CST wiring and brain lesion characteristics to predict UL motor and sensory functions in uCP. Fifty-two participants with uCP (mean age (SD): 11 y and 3 m (3 y and 10 m)) underwent a single-pulse Transcranial Magnetic Stimulation session to determine CST wiring between the motor cortex and the more affected hand (n = 17 contralateral, n = 19 ipsilateral, and n = 16 bilateral) and an MRI to determine lesion timing (n = 34 periventricular (PV) lesion, n = 18 corticosubcortical (CSC) lesion), location, and extent. Lesion location and extent were evaluated with a semiquantitative scale. A standardized protocol included UL motor (grip strength, unimanual capacity, and bimanual performance) and sensory measures. A combination of lesion locations (damage to the PLIC and frontal lobe) significantly contributed to differentiate between the CST wiring groups, reclassifying the participants in their original group with 57% of accuracy. Motor and sensory functions were influenced by each of the investigated neurological factors. However, multiple regression analyses showed that motor function was predicted by the CST wiring (more preserved in individuals with contralateral CST (p < 0.01)), lesion extent, and damage to the basal ganglia and thalamus. Sensory function was predicted by the combination of a large and later lesion and an ipsilateral or bilateral CST wiring, which led to increased sensory deficits (p < 0.05). These novel insights contribute to a better understanding of the underlying pathophysiology of UL function and may be useful to delineate individualized treatment strategies.

Project description:Transcranial magnetic stimulation (TMS) induced motor evoked potentials (MEPs) are an established proxy of corticospinal excitability. As a binary measure, the presence (MEP+) or absence (MEP-) of ipsilesional hemisphere MEPs early following stroke is a robust indicator of long-term recovery, however this measure does not provide information about spatial cortical reorganization. MEPs have been systematically acquired over the sensorimotor cortex to "map" motor topography. In this investigation we compared the degree to which functional improvements resulting from early (<3 months post-stroke) intensive hand focused upper limb rehabilitation correlate with changes in motor topography between MEP+ and MEP- individuals. Following informed consent, 17 individuals (4 Female, 60.3 ± 9.4 years, 24.6 ± 24.01 days post first time stroke) received 8 one hour-sessions of training with virtual reality (VR)/Robotic simulations. Clinical tests [Box and Blocks Test (BBT), Wolf Motor Function Test (WMFT), Upper Extremity Fugl-Meyer (UEFMA)], kinematic and kinetic assessments [finger Active Range of Motion (finger AROM), Maximum Pinch Force (MPF)], and bilateral TMS mapping of 5 hand muscles were performed prior to (PRE), directly following (POST), and 1 month following (1M) training. Participants were divided into two groups (MEP+, MEP-) based on whether an MEP was present in the affected first dorsal interosseous (FDI) at any time point. MEP+ individuals improved significantly more than MEP- individuals from PRE to 1M on the WMFT, BBT, and finger AROM scores. Ipsilesional hemisphere FDI area increased significantly with time in the MEP+ group. FDI area of the contralesional hemisphere was not significantly different across time points or groups. In the MEP+ group, significant correlations were observed between PRE-1M changes in ipsilesional FDI area and WMFT, BBT, and finger AROM, and contralesional FDI area and UEFMA and MPF. In the MEP- group, no significant correlations were found between changes in contralesional FDI area and functional outcomes. We report preliminary evidence in a small sample that patterns of recovery and the association of recovery to bilateral changes in motor topography may depend on integrity of the ipsilesional cortical spinal tract as assessed by the presence of TMS evoked MEPs.

Project description:BackgroundStroke patients are often affected by arm paresis, have functional impairments and receive help from professional or informal caregivers. Progressive resistance training is a common intervention for functional impairments after paresis. Randomised controlled trials (RCT) showed benefits for functional recovery after resistance training. However, there is a lack of evidence for strength training in subacute stroke patients. The aim of this study is to investigate safety and effectiveness of arm strength training in subacute stroke patients.MethodsWe will conduct a prospective, assessor-blinded RCT of people with subacute stroke. We will randomly assign patients to one of two parallel groups in a 1:1 ratio and will use concealed allocation. The intervention group will receive, in addition to standard treatment, high-intensity arm training (three times per week, over three weeks; 60 min each session; with a total of nine additional sessions). The control group will receive, in addition to standard treatment, low-intensity arm training (same quantity, frequency and treatment time as the intervention group). Standard treatment for the affected arm includes mobilisation, stretching, therapeutic positioning, arm and hand motor training, strengthening exercises, mechanical assisted training, functional training and task-oriented training. The primary efficacy endpoint will be grip strength. Secondary outcome measures will be Modified Ashworth Scale, Motricity Index, Fugl-Meyer Assessment for the upper limb, Box and Block Test and Goal Attainment Scale for individual participatory goals. We will measure primary and secondary outcomes with blinded assessors at baseline and immediately after three weeks of additional therapy. Based on our sample size calculation, 78 patients will be recruited from our rehabilitation hospital in two and a half years. Drop-out rates and adverse events will be systematically recorded.DiscussionThis study attempts to close the evidence gap for effects of arm strength training in subacute stroke patients. The results of this trial will provide robust evidence for effects and safety of high-intensity arm training for people with stroke.Trial registrationGerman Clinical Trials Register, DRKS00012484 . Registered on 26 May 2017.

Project description:BackgroundAs many as 80% of stroke survivors experience upper limb (UL) disability. The strong relationships between disability, lost productivity, and ongoing health care costs mean reducing disability after stroke is critical at both individual and society levels. Unfortunately, the amount of UL-focused rehabilitation received by people with stroke is extremely low. Activity monitoring and promotion using wearable devices offer a potential technology-based solution to address this gap. Commonly, wearable devices are used to deliver a haptic nudge to the wearer with the aim of promoting a particular behavior. However, little is known about the effectiveness of haptic nudging in promoting behaviors in patient populations.ObjectiveThis study aimed to estimate the effect of haptic nudging delivered via a wrist-worn wearable device on UL movement in people with UL disability following stroke undertaking inpatient rehabilitation.MethodsA multiple-period randomized crossover design was used to measure the association of UL movement with the occurrence of haptic nudge reminders to move the affected UL in 20 people with stroke undertaking inpatient rehabilitation. UL movement was observed and classified using movement taxonomy across 72 one-minute observation periods from 7:00 AM to 7:00 PM on a single weekday. On 36 occasions, a haptic nudge to move the affected UL was provided just before the observation period. On the other 36 occasions, no haptic nudge was given. The timing of the haptic nudge was randomized across the observation period for each participant. Statistical analysis was performed using mixed logistic regression. The effect of a haptic nudge was evaluated from the intention-to-treat dataset as the ratio of the odds of affected UL movement during the observation period following a "Planned Nudge" to the odds of affected limb movement during the observation period following "No Nudge."ResultsThe primary intention-to-treat analysis showed the odds ratio (OR) of affected UL movement following a haptic nudge was 1.44 (95% CI 1.28-1.63, P<.001). The secondary analysis revealed an increased odds of affected UL movement following a Planned Nudge was predominantly due to increased odds of spontaneous affected UL movement (OR 2.03, 95% CI 1.65-2.51, P<.001) rather than affected UL movement in conjunction with unaffected UL movement (OR 1.13, 95% CI 0.99-1.29, P=.07).ConclusionsHaptic nudging delivered via a wrist-worn wearable device increases affected UL movement in people with UL disability following stroke undertaking inpatient rehabilitation. The promoted movement appears to be specific to the instructions given.Trial registrationAustralia New Zealand Clinical Trials Registry 12616000654459; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370687&isReview=true.

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The Strength of the Corticospinal Tract Not the Reticulospinal Tract Determines Upper-Limb Impairment Level and Capacity for Skill-Acquisition in the Sub-Acute Post-Stroke Period.

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