Clinical applicability of automated tractography for stroke rehabilitation: Z-score conversion of fractional anisotropy.

[Purpose] To expand the applicability of diffusion-tensor tractography fractional anisotropy for stroke rehabilitation, this study aimed to provide references for representative neural tracts from non-lesioned hemispheres. Therefore, we applied the assessment of neural integrity to representative stroke patients using Z-score conversion. [Participants and Methods] Fractional anisotropy values were assessed in neural tracts, including the corticospinal tract, inferior fronto-occipital fasciculus, uncinate fasciculus, and anterior thalamic radiation, of stroke patients receiving acute care. [Results] Data were collected from 60 patients for the non-lesioned right hemisphere and 68 patients for the non-lesioned left hemisphere. Mean fractional anisotropy values in the corticospinal tract and inferior fronto-occipital fasciculus were notably elevated, reaching approximately 0.6 and 0.5, respectively. The mean fractional anisotropy values for other neural tracts were approximately 0.4, and, the overall standard deviations were approximately 0.04. In two typical stroke patients assessed using Z-scores, the scores in the corticospinal tract corresponded to the severity of the hemiparesis. The scores in the anterior thalamic radiation and inferior fronto-occipital fasciculus were associated with more significant brain dysfunction, including inattention and aphasia. [Conclusion] In this study, the Z-score findings related to stroke symptoms align with those reported in the literature, indicating the appropriateness of the methodology used and its potential in future applications.

Evidence and Recommendations for Acute Stroke Rehabilitation from the Japan Stroke Society: Abridged Secondary Publication of the Japanese-language Version.

Objectives: In Japan, acute stroke rehabilitation has been expanding more steadily than previously with the nationwide establishment of primary stroke centers. However, Japan previously had no established guidelines for the rehabilitation. Consequently, rehabilitation programs and the provision systems for acute stroke varied among the facilities. To equalize and standardize acute stroke rehabilitation in Japan, it is necessary to develop clinical recommendations for rehabilitation. Therefore, the rehabilitation project team of the Japan Stroke Society aimed to develop the first recommendations for acute stroke rehabilitation in Japan. Methods: The recommendations are based on the results of a survey on the current status of acute stroke rehabilitation at primary stroke centers in Japan, which was completed in 2022, and on a literature review conducted by the rehabilitation project team. Results: The recommendations consist of 19 clinical questions regarding the following topics of acute stroke rehabilitation: (1) head elevation and mobilization training, (2) acute complications, (3) training time and frequency for acute stroke rehabilitation, (4) dysphagia in the acute phase, and (5) acute rehabilitation during pandemics of novel and re-emerging infections, particularly novel coronavirus disease 2019 (COVID-19). The team members agreed on all answers for these 19 clinical questions. Conclusions: These recommendations suggest broad principles of rehabilitative intervention in the acute phase of stroke. In the near future, it is expected that the dissemination of these recommendations will result in an increase in the quality of acute stroke rehabilitation in Japan.

Synthetic assembly of α-O-linked-type GlcNAc using polymer chemistry affords sugar clusters, which effectively bind to lectins.

Fischer's glycoside synthesis was applied to linker precursor alcohols of two different lengths having appropriate alkane chains to obtain the corresponding α-glycoside and it was found to be applicable with moderate yields. Water-soluble glycomonomers were systematically prepared from N-acetyl-d-glucosamine (GlcNAc) by introducing two kinds of alcohols having different methylene lengths. Typical radical polymerizations of the glycomonomers with acrylamide as a modulator for control of the distance between carbohydrate residues in water in the presence of ammonium persulfate (APS)-N,N,N',N'-tetramethylethylenediamine (TEMED) gave a series of glycopolymers with various α-glycoside-type GlcNAc residue densities. Fluorometric analysis of the interaction of wheat germ agglutinin (WGA) with the glycopolymers was performed and the results showed unique binding specificities based on structural differences.

Outcome Prediction by Combining Corticospinal Tract Lesion Load with Diffusion-tensor Fractional Anisotropy in Patients after Hemorrhagic Stroke.

Objectives: The objective of this study was to evaluate the predictive precision of combining the corticospinal tract lesion load (CST-LL) with the diffusion-tensor fractional anisotropy of the corticospinal tract (CST-FA) in the lesioned hemispheres regarding motor outcomes. Methods: Patients with putaminal and/or thalamic hemorrhage who had undergone computed tomography (CT) soon after onset in our hospital were retrospectively enrolled. The CST-LL was calculated after registration of the CT images to a standard brain. Diffusion-tensor imaging was performed during the second week after onset. Standardized automated tractography was employed to calculate the CST-FA. Outcomes were assessed at discharge from our affiliated rehabilitation facility using total scores of the motor component of the Stroke Impairment Assessment Set (SIAS-motor total; null to full, 0 to 25). Multivariate regression analysis was performed with CST-LL and CST-FA as explanatory variables and SIAS-motor total as a target value. Results: Twenty-five patients participated in this study. SIAS-motor total ranged from 0 to 25 (median, 17). CST-LL ranged from 0.298 to 7.595 (median, 2.522) mL, and the lesion-side CST-FA ranged from 0.211 to 0.530 (median, 0.409). Analysis revealed that both explanatory variables were detected as statistically significant contributory factors. The estimated t values indicated that the contributions of these two variables were almost equal. The obtained regression model accounted for 63.9% of the variability of the target value. Conclusions: Incorporation of the CST-LL with the lesion-side CST-FA enhances the precision of the stroke outcome prediction model.

Impact of functional independence and sociodemographic factors on post-stroke discharge destination in a super-aged rural community in Japan.

Objective: This study aimed to clarify the factors influencing the discharge destination of stroke patients in a super-aged rural community in Japan, focusing on functional independence and sociodemographic factors. Patients and Methods: We enrolled patients recovering from stroke with supratentorial lesions who were admitted to our convalescent rehabilitation hospital. The motor components of the Functional Independence Measure (FIM-motor) were assessed for each patient at admission and discharge as explanatory variables. An increase in the FIM-motor scores during hospitalization was also recorded. Additionally, sociodemographic data such as sex, age, and clinical characteristics, such as type of stroke, history of stroke, days from stroke onset to transfer to our convalescent rehabilitation hospital, total duration of hospital stay including acute care, number of co-resident household members, living with a spouse, and number of children were collected. As target values, discharge outcomes were categorized into two groups: returning home and going to a nursing home. Logistic regression analysis was performed. Results: The study sample comprised 160 patients (mean age ± standard deviation, 74.80 ± 12.19 years). Of these, 114 were discharged to their homes, and 46 were transferred to nursing homes. The results of multivariate logistic regression analysis indicated that higher FIM-motor scores at discharge, greater number of co-resident household members, and living with one's spouse were the most powerful predictors of a higher probability of returning home. Conclusion: This study demonstrated that functional independence levels and the number of co-resident household members were crucial factors in predicting the discharge destination of patients after stroke in a super-aged rural community in Japan. These findings imply that for older patients with lower functional independence, supportive social networks are essential for home discharge, offering clues for providing long-term healthcare in super-aged rural communities worldwide.

Timing of Initiation of Acute Stroke Rehabilitation and Management Corresponding to Complications at Primary Stroke Centers in Japan: A Nationwide Cross-Sectional Web-Based Questionnaire Survey.

INTRODUCTION: Many guidelines now recommend early rehabilitation for acute stroke patients. However, evidence remains lacking regarding the specific timings for initiation of various rehabilitation steps and management when complications are encountered in acute stroke rehabilitation. This survey aimed to investigate actual clinical situations in acute stroke rehabilitation in Japan and to improve the medical systems for rehabilitation and plan further studies. METHODS: This nationwide, cross-sectional, web-based questionnaire survey was administered between February 7, 2022, and April 21, 2022, targeting all primary stroke centers (PSCs) in Japan. Among several components of the survey, this paper focused on the timing of the initiation of three rehabilitation steps (passive bed exercise; head elevation; and out-of-bed mobilization), along with the management of rehabilitation (continued or suspended) in the event of complications during acute stroke rehabilitation. We also investigated the influence of facility features on these contents. RESULTS: Responses were obtained from 639 of the 959 PSCs surveyed (response rate: 66.6%). In cases of ischemic stroke and intracerebral hemorrhage, most PSCs initiated passive bed exercise on day 1, head elevation on day 1, and out-of-bed mobilization on day 2 (with day of admission defined as day 1). In cases with subarachnoid hemorrhage, rehabilitation steps were delayed compared to other stroke subtypes or showed wide variation depending on the facility. Passive bed exercise was accelerated by the presence of protocols for rehabilitation and weekend rehabilitation. Out-of-bed mobilization was accelerated by the presence of a stroke care unit. Facilities with board-certified rehabilitation doctors were cautious regarding the initiation of head elevation. Most PSCs suspended rehabilitation training in the event of symptomatic systemic/neurological complications. CONCLUSION: Our survey revealed the actual situation of acute stroke rehabilitation in Japan and indicated that some facility features appear to influence early increases in physical activity levels and early mobilization. Our survey provides fundamental data to improve the medical systems for acute stroke rehabilitation in the future.

A nationwide survey for the provision of acute stroke rehabilitation in Japan: initial dose and weekend/holiday rehabilitation.

OBJECTIVES: The early initiation of acute stroke rehabilitation with a sufficient dose, including at weekends/holidays, is important to improve functional outcome. We investigated the status of acute stroke rehabilitation in Japan by using a nationwide survey. MATERIALS AND METHODS: Facility features, rehabilitation dose provided in the first week in each stroke subtype, and weekend/holiday rehabilitation were investigated by using the results of a web-based survey among primary stroke centers. The relationships between facility features and weekend/holiday rehabilitation were also analyzed. RESULTS: A total of 639 stroke centers (66.6%) completed the questionnaire. The overall median dose was 2.0 (interquartile range, 1.7-3.0) U/day (1U = 20 min). After 7 days, the overall median dose increased to 4.0 (2.0-5.4) U/day. Almost 50% of facilities replied that they could not provide a sufficient dose of rehabilitation; the main reason was a lack of therapists (31%). For rehabilitation on long weekends, no rehabilitation was provided on 3-day weekends in 19% of facilities, and in 5% of facilities on ≥4-day weekends. The mean number of therapists was almost 50% less in the facilities that provided no rehabilitation on 3-day weekends compared to those that provided daily rehabilitation (19.4 vs. 36.2 therapists, respectively, p < 0.001). CONCLUSIONS: In this survey, the provision of acute stroke rehabilitation, including non-working days, was clarified. According to the results, prospective interventional or observational studies are needed to design more effective rehabilitation programs to improve outcome. In particular, it is important to determine the optimal dose and intensity of acute stroke rehabilitation.

Applicability of fractional anisotropy from standardized automated tractography for outcome prediction of patients after stroke.

[Purpose] Diffusion-tensor fractional anisotropy has been used for outcome prediction in stroke patients. We assessed the clinical applicability of the two major fractional anisotropy methodologies-fractional anisotropy derived from segmentation maps in the standard brain (region of interest) and fractional anisotropy derived from standardized automated tractography-in relation to outcomes. [Participants and Methods] The study design was a retrospective survey of medical records collected from October 2021 to September 2022. Diffusion-tensor imaging was conducted in the second week after stroke onset. Outcomes were assessed using the total score of the motor component of the Stroke Impairment Assessment Set (null to full, 0 to 25). Correlations between fractional anisotropy and the outcomes were then assessed. [Results] Fourteen patients with hemorrhagic stroke were sampled. The fractional anisotropy from standardized automated tractography of the corticospinal tract on the lesion side (mean ± standard deviation, 0.403 ± 0.070) was significantly and tightly correlated (r=0.813) with the outcomes (13.4 ± 9.2), whereas the fractional anisotropy from a region of interest set in the cerebral peduncle on the lesion side (0.548 ± 0.064) was not significantly correlated with the outcomes (r=0.507). [Conclusion] The findings suggest that fractional anisotropy derived from standardized automated tractography can be more applicable to outcome prediction than that derived from a region of interest defined in the standard brain.

Automated Tractography for the Assessment of Aphasia in Acute Care Stroke Rehabilitation: A Case Series.

Background: Aphasia is a common disorder among stroke patients. Assessment of aphasia is essential for scheduling appropriate rehabilitative treatment. Although this is conventionally accomplished using neuropsychological test batteries, these tests are not always accessible because of attention and/or consciousness disturbances during acute care. To overcome this issue, we have introduced a newly developed automated tractography known as XTRACT. Cases: Diffusion-tensor images were acquired from three patients on days 10-14. Brain images were processed by XTRACT, which automatically extracts neural tracts using standardized protocols. Fractional anisotropy (FA) values were then bilaterally evaluated in the following neural tracts associated with aphasia: arcuate fasciculus, inferior fronto-occipital fasciculus, middle longitudinal fasciculus, inferior longitudinal fasciculus, and uncinate fasciculus. Case 1 had word-finding difficulty on admission. FA values in the lesioned left hemisphere were not decreased in all tracts and this patient fully recovered during acute care. Case 2 had reduced spontaneous speech and a low FA value in the left arcuate fasciculus. Rehabilitative treatment was scheduled to improve the verbal output of sentences and word recall. Case 3 could not complete the conventional aphasia test battery because of attention disturbance. He had low FA values in all tracts in the left hemisphere. Rehabilitative treatment was designed to focus on both speaking and auditory comprehension. Discussion: Automated tractography enables quantitative assessment of the neural damage associated with aphasia, even in patients with attention and/or consciousness disturbances. This modality can aid in the assessment of aphasia and allows the planning of appropriate rehabilitative treatment.

Preparation of N-Linked-Type GlcNAc Monomers for Glycopolymers and Binding Specificity for Lectin.

Glycomonomers having N-glycosidic linkages were prepared from a known glycosyl amine, N-acetyl-d-glucosamine (GlcNAc). Radical polymerization of the glycomonomers gave a series of glycopolymers displaying various sugar densities, which were models of the core structure of Asn-linked-type glycoproteins. In addition, fluorometric analyses of wheat germ agglutinin (WGA) against the glycopolymers were carried out, and the results showed unique binding specificities on the basis of flexibility of sugar moieties.

Preparation of a Water-Soluble Glycopolymer Bearing Porphyrin Skeletons and Its Biological Properties.

A known tetraphenyl porphyrin (TPP) having an amino functional group [5-(4-aminophenyl)-10,15,20-(triphenyl)porphyrin] was converted into the corresponding monomer by means of condensation with acryloyl chloride. Simple radical polymerization of the porphyrin monomer and a glycosyl monomer in the presence of acrylamide as a regulator monomer in order to avoid steric interference gave a water-soluble glycopolymer bearing porphyrin moieties. Spectroscopic analyses suggested incorporation of porphyrin moieties in the glycopolymer. The physical properties of the water-soluble glycopolymer bearing porphyrin moieties were examined in aqueous media, and the results also indicated the incorporation of TPP moieties in the polymer. Uptake of the polymer into HeLa cells was observed, and the cytotoxicity of the polymer was confirmed by microscopic analyses. The glycopolymer bearing porphyrin moieties is promising not only for photodynamic therapy but also as an anti-cancer reagent.

Proteolytic polymer: polyacrylamides functionalized with amino acids cleave bovine and human serum albumins.

Polyacrylamides with various compositions of serine, aspartic acid, and histidine, which are the amino acids involved in the catalytic triad of natural serine protease chymotrypsin, were synthesized and their protein cleavage activity was investigated. SDS-PAGE analysis showed that some of the synthesized ternary copolymers showed cleavage activity against bovine and human serum albumins. Polyacrylamides incorporating a single type of amino acid were also able to cleave the protein substrates. These homopolymers exhibited unique cleavage profiles and pH and temperature sensitivities that differed from those of α-chymotrypsin. The results indicate the potential of polymers functionalized with amino acids as proteolytic artificial enzymes.

ICU-Acquired Weakness Complicated With Bilateral Foot Drop After Severe COVID-19: Successful Rehabilitation Approach and Long-Term Follow-Up.

Coronavirus disease 2019 (COVID-19) is associated with muscle and nerve injuries as a consequence of prolonged critical illness. We report here a case of intensive care unit-acquired weakness (ICU-AW) with bilateral peroneal nerve palsy after COVID-19. A 54-year-old male with COVID-19 was transferred to our hospital. He was treated by mechanical ventilation and veno-venous extracorporeal membrane oxygenation (VV-ECMO), from which he was successfully weaned. However, by day 32 of ICU admission, he had developed generalized muscle weakness with bilateral foot drop and was diagnosed with intensive care unit-acquired weakness complicated with bilateral peroneal nerve palsy. Electrophysiological examination showed a denervation pattern in the tibialis anterior muscles, indicating that the foot drop was unlikely to recover immediately. Gait training with customized ankle-foot orthoses (AFO) and muscle-strengthening exercises were started as part of a regimen that included a stay in a convalescent rehabilitation facility and outpatient rehabilitation. Seven months after onset, he returned to work, and 18 months after onset, he had improved to the same level of activities of daily living (ADLs) as before onset. Outcome prediction by electrophysiological examination, appropriate prescription of orthoses, and continuous rehabilitative treatment that focused on locomotion contributed to the successful outcome in this case.

Brain regions associated with Brunnstrom and functional independence measure scores in patients after a stroke: a tract-based spatial statistics study.

[Purpose] We aimed to assess diffusion tensor fractional anisotropy to outline the brain regions associated with the long-term motor and cognitive functional outcomes of patients with stroke. [Participants and Methods] Eighty patients from our previous study were enrolled. Fractional anisotropy maps were acquired on days 14-21 after stroke onset, and tract-based spatial statistics were applied. Outcomes were scored using the Brunnstrom recovery stage and Functional Independence Measure motor and cognition components. Fractional anisotropy images were assessed in relation to outcome scores using the general linear model. [Results] For both the right (n=37) and left (n=43) hemisphere lesion groups, the corticospinal tract and the anterior thalamic radiation were most strongly associated with the Brunnstrom recovery stage. In contrast, the cognition component involved large regions encompassing the anterior thalamic radiation, superior longitudinal fasciculus, inferior longitudinal fasciculus, uncinate fasciculus, cingulum bundle, forceps major, and forceps minor. The results for the motor component were intermediate between those for the Brunnstrom recovery stage and those for the cognition component. [Conclusion] Motor-related outcomes were associated with fractional anisotropy decreases in the corticospinal tract, whereas cognitive outcomes were related to broad regions of association and commissural fibers. This knowledge will help scheduling appropriate rehabilitative treatments.

Use of a Longer Aglycon Moiety Bearing Sialyl α(2→3) Lactoside on the Glycopolymer for Lectin Evaluation.

A polymerizable alcohol having 9 PEG repeats was prepared in order to mimic an oligosaccharide moiety. Sialyl α(2→3) lactose, which is known as a sugar moiety of GM3 ganglioside, was also prepared, and the polymerizable alcohol was condensed with the sialyl α(2→3) lactose derivative to afford the desired glycomonomer, which was further polymerized with or without acrylamide to give water-soluble glycopolymers. The glycopolymers had higher affinities than those of glycopolymers having sialyl lactose moieties with shorter aglycon moieties.

Applicability of automated tractography during acute care stroke rehabilitation.

[Purpose] To assess the clinical applicability of a novel automated tractography tool named XTRACT during acute stroke rehabilitation. [Participants and Methods] Three patients with left hemisphere stroke were sampled. Diffusion tensor images were acquired on the second week, and automated tractography was then applied. Tractography images and fractional anisotropy (FA) values in the corticospinal tract (CST) and arcuate fasciculus (AF) were assessed in relation to hemiparesis and aphasia. [Results] Patient 1 was nearly asymptomatic; FA in the left CST was 0.610 and that in the AF was 0.509. Patient 2 had severe hemiparesis and mild motor aphasia. Tractography images of the CST and AF were blurred; FA in the left CST was 0.295 and that in the AF was 0.304. Patient 3 showed no hemiparesis or aphasia at initial assessment. Tractography image of the CST was intact but that of the AF was less clear; FA in the left CST was 0.586 and that in the AF was 0.338. Considering the less clear images of the AF and lower FA value in Patients 2 and 3, further examinations for aphasia were performed, which revealed agraphia. [Conclusion] Visualization and quantification of neural fibers using automated tractography promoted planning acute care rehabilitative treatment in patients with stroke.

Synthetic assembly of a series of glycopolymers having sialyl α2-3 lactose moieties connected with longer spacer arms.

Glycopolymers having sialyl α2-3 lactose moieties via longer spacer arms were systematically prepared from the corresponding glycomonomers. Radical polymerization of glycomonomers gave a series of glycopolymers displaying various sugar densities. Fluorometric analyses of wheat germ agglutinin (WGA) against the glycopolymers were conducted and the results showed unique binding specificities on the basis of sugar densities.

Modification of Fab Fragments by Dibromopyridazinediones Carrying Mono- and Double-Biotin Functionalities.

To verify the potencies of dibromopyridazinediones with mono- and double-biotin groups, the functions as cysteine-selective biotinylation reagents were evaluated through conjugation with a goat anti-mouse IgG Fab fragment as a functional protein model. The starting Fab was reduced with tris(2-carboxyethyl)phosphine to cleave the disulfide bond and then treated with the reagents. These reagents simultaneously introduced biotin groups into the reduced Fab and re-bridged the disulfide moiety. Furthermore, we demonstrated that the biotin-labeled Fabs were reactive to an antigen and streptavidin.

Dendritic maleimide-thiol adducts carrying pendant glycosides as high-affinity ligands.

We synthesized N-acetylglucosamine-terminated hexavalent carbosilane dendrimers and investigated their binding to wheat germ agglutinin (WGA). The glycodendrimers were prepared by the conjugation of 3-mercaptopropyl, 4-mercaptobutyl, or 5­mercaptopentyl glycosides to maleimide-terminated hexavalent carbosilane dendrimers. Titration of WGA with the glycodendrimers yielded quenching of tryptophan fluorescence. All of the glycodendrimers exhibited high affinity with nanomolar dissociation constants (KD values). The best dendrimers were 1a and 1b with KD values of 6.5 ± 1.7 and 5.3 ± 1.7 nM, respectively. The magnitude of fluorescence quenching increased with decrease in the length of the thioalkyl spacer. Maleimide-pendant carbosilane dendrimers provide ready access to multivalent ligands with high-affinity potential.

Relationship between the independence level of individual motor-related functional independence measure items and its total score in patients after hip fracture: an ordinal logistic modelling study.

[Purpose] The independence level of activities of daily living during the recovery period should be predicted to plan a rehabilitation program. This study aimed to assess the relationship between the independence levels of individual motor-related Functional Independence Measure (FIM-motor) items and total FIM-motor score in patients after hip fracture. [Participants and Methods] This study retrospectively analyzed 40 patients who had stayed in a convalescent rehabilitation hospital after hip fracture. The FIM-motor score was assessed for each patient on admission, after 2 and 4 weeks of hospitalization, and at discharge. [Results] The median FIM-motor scores were 52.5 on admission and 83.0 at discharge. The results of ordinal logistic modeling were statistically significant for all 13 FIM-motor items. The independence levels for transfer to toilet and bed/chair/wheelchair were proportionally distributed across the entire range of total FIM-motor scores. However, a weak relationship was observed between the scores for bladder and bowel management and total FIM-motor scores. Although eating and grooming were relatively easy items, stair-climbing and locomotion were difficult. [Conclusion] The relationship between the independence level of individual FIM-motor items and the total FIM-motor score varied widely. This knowledge might be useful while scheduling rehabilitative treatments for patients after hip fracture.