Changes in skeletal muscle function during chemotherapy and related factors in patients with acute leukemia.

INTRODUCTION: Skeletal muscle function is an important prognostically relevant indicator in patients with acute leukemia (AL), but skeletal dysfunction during chemotherapy is not well understood. This study aimed to investigate the factors that influence changes in skeletal muscle function from before the start of chemotherapy to before allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: This was a retrospective cohort study that included 90 patients with AL who underwent chemotherapy before transplantation to perform allo-HSCT (men, 67.3%; median age, 53 years). The outcome measure was defined as changes in skeletal muscle function from before chemotherapy to before allo-HSCT, and was assessed by measuring the psoas muscle index (PMI) as skeletal muscle quantity and computed tomography values (CTV) as skeletal muscle quality using a computed tomography scanner. We examined the differences in PMI and CTV before chemotherapy and allo-HSCT, and the factors associated with changes in PMI. RESULT: The mean PMI for before chemotherapy and allo-HSCT were 4.6 ± 1.4 cm2/m2 and 4.0 ± 1.3 cm2/m2 and significant differences were observed (p < 0.001). However, the mean CTV before chemotherapy and allo-HSCT were 47.3 ± 4.5 HU and 47.4 ± 5.0 HU, respectively, and no significant differences were found (p = 0.798). In stepwise multiple regression analysis, age and sex were identified as factors related to changes in PMI (age, p = 0.019; sex, p = 0.001). CONCLUSION: We found that skeletal muscle quantity decreased during chemotherapy in patients with AL and was influenced by male sex and older age. TRIAL REGISTRATION NUMBER:   TRIAL REGISTRATION NUMBER: 34-096(11,243). Date of registration: September 11, 2023.

Recovery of Patients With Upper Limb Paralysis Due to Stroke Who Underwent Intervention Using Low-Frequency Repetitive Transcranial Magnetic Stimulation Combined With Occupational Therapy: A Retrospective Cohort Study.

OBJECTIVES: The combination of repetitive transcranial magnetic stimulation (rTMS) and motor practice is based on the theory of neuromodulation and use-dependent plasticity. Predictive planning of occupational therapy (OT) is important for patients with rTMS conditioning. Recovery characteristics based on the severity of pretreatment upper extremity paralysis can guide the patient's practice plan for using the paretic hand. Therefore, we evaluated the recovery of patients with upper limb paralysis due to stroke who underwent a novel intervention of rTMS combined with OT (NEURO) according to the severity of upper limb paralysis based on the scores of the Fugl-Meyer assessment for upper extremity (FMA-UE) with recovery in proximal upper extremity, wrist, hand, and coordination. MATERIALS AND METHODS: In this multicenter retrospective cohort study, the recovery of 1397 patients with upper limb paralysis was analyzed by severity at six hospitals that were accredited by the Japanese Stimulation Therapy Society for treatment. The delta values of the FMA-UE scores before and after NEURO were compared among the groups with severe, moderate, and mild paralysis using the generalized linear model. RESULTS: NEURO significantly improved the FMA-UE total score according to the severity of paralysis (severe = 5.3, moderate = 6.0, and mild = 2.9). However, when the FMA-UE subscores were analyzed separately, the results indicated specific improvements in shoulder/elbow, wrist, fingers, and coordination movements, depending on the severity. CONCLUSIONS: This study had enough patients who were divided according to severity and stratified by lesion location and handedness parameters. Our results suggest that independently of these factors, the extent of recovery of upper limb motor parts after NEURO varies according to the severity of paralysis.

Magnetic Control of Cells by Chemical Fabrication of Melanin.

Melanin is an organic material biosynthesized from tyrosine in pigment-producing cells. The present study reports a simple method to generate tailored functional materials in mammalian cells by chemically fabricating intracellular melanin. Our approach exploits synthetic tyrosine derivatives to hijack the melanin biosynthesis pathway in pigment-producing cells. Its application was exemplified by synthesizing and using a paramagnetic tyrosine derivative, m-YR, which endowed melanoma cells with responsiveness to external magnetic fields. The mechanical force generated by the magnet-responsive melanin forced the cells to elongate and align parallel to the magnetic power lines. Critically, even non-pigment cells were similarly remote-controlled by external magnetic fields once engineered to express tyrosinase and treated with m-YR, suggesting the versatility of the approach. The present methodology may potentially provide a new avenue for mechanobiology and magnetogenetic studies and a framework for magnetic control of specific cells.

Chemoproteomic Identification of Blue-Light-Damaged Proteins.

Visible light, particularly in the blue region of the spectrum, can cause cell dysfunction through the generation of singlet oxygen, contributing to cellular aging and age-related pathologies. Although photooxidation of nucleic acids, lipids, and amino acids has been extensively studied, the magnitude and span of blue-light-induced protein damages within proteome remain largely unknown. Herein we present a chemoproteomic approach to mapping blue-light-damaged proteins in live mammalian cells by exploiting a nucleophilic alkyne chemical probe. A gene ontology enrichment analysis revealed that cell surface proteins are more readily oxidized than other susceptible sets of proteins, including mitochondrial proteins. In particular, the integrin family of cell surface receptors (ITGs) was highly ranked in the mammalian cells tested, including human corneal endothelial cells. The blue-light-oxidized ITGB1 protein was functionally inactive in promoting cell adhesion and proliferation, suggesting that the photodamage of integrins contributes to the blue-light-induced cell dysfunction. Further application of our method to various cells and tissues should lead to a comprehensive analysis of light-sensitive proteins.

Claw Toe: Anatomic Guide for Injection of Botulinum Toxin into Foot Muscles.

BACKGROUND: Poor response to injection of botulinum toxin (BoNT) into the flexor digitorum longus (FDL) muscle has been reported especially in patients with claw foot deformity. We previously advocated BoNT injection into the flexor hallucis longus (FHL) muscle in such patients. Here, we determined the functional and anatomical relationships between FHL and FDL. METHODS: Toe flexion pattern was observed during electrical stimulation of FHL and FDL muscles in 31 post-stroke patients with claw-foot deformity treated with BoNT. The FHL and FDL tendon arrangement was also studied in five limbs of three cadavers. RESULTS: Electrical stimulation of the FHL muscle elicited big toe flexion in all 28 cases examined and second toe in 25, but the response was limited to the big toe in 3. FDL muscle stimulation in 29 patients elicited weak big toe flexion in 1 and flexion of four toes (2nd to 5th) in 16 patients. Cadaver studies showed division of the FHL tendon with branches fusing with the FDL tendon in all five limbs examined; none of the tendons was inserted only in the first toe. No branches of the FDL tendon merged with the FHL tendon. CONCLUSION: Our results showed coupling of FHL and FDL tendons in most subjects. Movements of the second and third toes are controlled by both the FDL and FHL muscles. The findings highlight the need for BoNT injection in both the FDL and FHL muscles for the treatment of claw-toe deformity.

Changes in brain morphometry after motor rehabilitation in chronic stroke.

PURPOSE: Recent studies have revealed structural changes after motor rehabilitation, but its morphological changes related to upper limb motor behaviours have not been studied exhaustively. Therefore, we aimed to map the grey matter (GM) changes associated with motor rehabilitation after stroke using voxel-based morphometry (VBM), deformation-based morphometry (DBM), and surface-based morphometry (SBM). METHODS: Forty-one patients with chronic stroke received twelve sessions of low-frequency repetitive transcranial magnetic stimulation plus intensive occupational therapy. MRI data were obtained before and after the intervention. Fugl-Meyer Assessment and Wolf Motor Function Test-Functional Ability Scale were assessed at the two-time points. We performed VBM, DBM, and SBM analyses using T1-weighted images. A correlation analysis was performed between cortical thickness in motor areas and clinical outcomes. RESULTS: Clinical outcomes significantly improved after the intervention. VBM showed significant GM volume changes in ipsilesional and contralesional primary motor regions. DBM results demonstrated GM changes contralesionally and ipsilesionally after the intervention. SBM results showed significant cortical thickness changes in posterior visuomotor coordination, precentral, postcentral gyri of the ipsilesional hemisphere and contralesional visuomotor area after the intervention. A combination of threshold p < .05, False Discovery Rate and p < .001 (uncorrected) were considered significant. In addition, cortical thickness changes of the ipsilesional motor areas were significantly correlated with the clinical outcome changes. CONCLUSIONS: We found GM structural changes in areas involved in motor, visuomotor and somatosensory functions after the intervention. Furthermore, our findings suggest that structural plasticity changes in chronic stroke could occur in the ipsilesional and contralesional hemispheres after motor rehabilitation.

Botulinum toxin treatment for difficult-to-treat finger pressure ulcers caused by severe hand flexion: case report.

We report the successful treatment of two cases of difficult-to-treat pressure ulcers with botulinum toxin type A (BoNT-A). A 71-year-old male patient with Parkinson's disease presented with severe hand grip deformities of the fingers and a pressure ulcer (PU) on the right hand. He received 240U of BoNT-A into the upper limb muscles, which improved finger mobility during passive extension and resulted in resolution of the palm PU. No recurrence was noted. A 69-year-old female patient with Lewy body dementia presented with a PU on the palm side of the middle finger apex of the right hand, with exposure of the phalanx bone and dark red oedematous granulation of the tip of the finger. Severe muscle tone was noted. She received 240U of BoNT-A injected into the muscles of the upper extremities. This resulted in the disappearance of the contracture between the middle finger cusp and palm, and prompt healing of the PU. A protective finger orthosis was also used to improve hand finger grip and prevent further PUs. Although BoNT-A injection resulted in only slight improvement in the range of motion, it produced relief of pressure with consequent healing of the PU. Injection of BoNT-A into the affected muscles of the patients in this case report was effective in reducing flexor muscle tone, relief of pressure on the palm skin and healing of hand PUs.

Chemical Genetics Reveals a Role of Squalene Synthase in TGFß Signaling and Cardiomyogenesis.

KY02111 is a widely used small molecule that boosts cardiomyogenesis of the mesoderm cells derived from pluripotent stem cells, yet its molecular mechanism of action remains elusive. The present study resolves the initially perplexing effects of KY02111 on Wnt signaling and subsequently identifies squalene synthase (SQS) as a molecular target of KY02111 and its optimized version, KY-I. By disrupting the interaction of SQS with cardiac ER-membrane protein TMEM43, KY02111 impairs TGFß signaling, but not Wnt signaling, and thereby recapitulates the clinical mutation of TMEM43 that causes arrhythmogenic right ventricular cardiomyopathy (ARVC), an inherited heart disease that involves a substitution of myocardium with fatty tissue. These findings reveal a heretofore undescribed role of SQS in TGFß signaling and cardiomyogenesis. KY02111 may find its use in ARVC modeling as well as serve as a chemical tool for studying TGFß/SMAD signaling.

Preoperative rehabilitation for patients undergoing colorectal cancer surgery: a retrospective cohort study.

PURPOSE: We investigated the impact of preoperative short-term rehabilitation on activities of daily living among patients with colorectal cancer. METHODS: This retrospective cohort study utilized a hospital-based database containing Diagnosis Procedure Combination survey data from over 100 participating acute-care hospitals. We extracted data on consecutive inpatients hospitalized with stage 1 and 2 colorectal cancer. We compared characteristics and outcomes between patients who underwent short-term rehabilitation before surgery and those who did not. Primary outcomes measured were Barthel Index decline and number of complications during hospitalization. RESULTS: Among of included inpatients (male, 57%; older individuals aged over 65 years, 79%; mean Barthel Index, 93.4), the number of patients who underwent preoperative rehabilitation was 760 (39.3%). Patients in the preoperative rehabilitation group were less likely to have a decline in the Barthel Index compared with the control group (5.9% vs 10.1%, P < 0.001) and after propensity score adjustment using inverse probability weighting (6.3% vs 9.8%, P = 0.024). The preoperative rehabilitation group had fewer complications during hospitalization compared with the control group (P < 0.001) and after inverse probability weighting (P = 0.001). CONCLUSION: Our study showed that preoperative short-term rehabilitation was associated with maintenance and improvement of activities of daily living and fewer complications among patients with stage 1 and 2 colorectal cancer.

MRI evaluation of motor function recovery by rTMS and intensive occupational therapy and changes in the activity of motor cortex.

Purpose/aim: An intervention that combines low-frequency repetitive transcranial magnetic stimulation and intensive occupational therapy can improve brain function in post-stroke patients with motor paralysis. The purpose of the present study is examined motor function recovery by repetitive transcranial magnetic stimulation and intensive occupational therapy and changes in the activity of motor cortex based on magnetic resonance imaging data.Materials and methods: In total, we assessed 30 patients with post-stroke upper extremity paralysis who were hospitalized for 12 sessions of low-frequency repetitive transcranial magnetic stimulation over the lesion-free hemisphere plus daily occupational therapy for 15 days. Imaging analysis was performed using 3-dimensional T1-weighted image and functional magnetic resonance imaging. Hemispheric dominance was assessed by functional magnetic resonance imaging using the laterality index. In addition, Seed-based functional connectivity analysis was used to evaluate functional connectivity between the precentral gyrus of the affected side and other areas.Results: A positive correlation was found between laterality index before intervention and the Brunnstrom recovery stage for hand/fingers (p < 0.05). The intervention resulted in significantly higher functional connectivity between the precentral gyrus of the affected side and that of the healthy side (false discovery rate corrected p < 0.05).Conclusions: We clarified that the recovery of motor function by intervention with low-frequency repetitive transcranial magnetic stimulation and occupational therapy and the increase of functional connectivity between the precentral gyrus on the affected side and the healthy side are related. These results facilitate prognostic predictions and evidence-based medical care.

The 2-Minute Spontaneous Swallowing Screening Predicts Independence on Enteral Feeding in Patients with Acute Stroke.

BACKGROUND: It is recommended that enteral feeding should be offered to patients with dysphagia estimated to be unable to take adequate diet orally within 7 days of admission after acute stroke, but there is no clear criterion for initiation of enteral feeding. Recent studies have reported that the frequency of spontaneous swallowing is useful in screening for dysphagia in acute stroke. The present study was aimed to investigate whether measurement of frequency of spontaneous swallowing for 2 minutes could predict independence on enteral feeding 1 week after admission in patients with acute stroke. METHODS: Patients with acute stroke were subjected. Within 72 hours of stroke onset, the number of swallows for 2 minutes was measured by auscultation. Subsequently, 1-hour frequency of spontaneous swallowing was measured using a laryngeal microphone. Functional Oral Intake Scale (FOIS) was evaluated 1 week after admission. RESULTS: Twenty-six out of 40 patients were independent on enteral feeding 1 week after admission based on FOIS. The presence of spontaneous swallowing for 2 minutes had .89 sensitivity, .54 specificity to predict independence on enteral feeding 1 week after admission, whereas the 1-hour frequency of spontaneous swallowing had 1.00 sensitivity, .46 specificity. Logistic regression analysis demonstrated that the presence of spontaneous swallowing for 2 minutes was independent predictor for independence on enteral feeding 1 week after admission, independently of age, sex, and NIHSS. CONCLUSIONS: The 2-minute spontaneous swallowing screening predicts independence on enteral feeding 1 week after admission in patients with acute stroke.

Role of D-serine in the beneficial effects of repetitive transcranial magnetic stimulation in post-stroke patients.

OBJECTIVE: Abnormalities in neurotransmission via N-methyl-D-aspartic acid receptor (NMDAR) play a role in the pathophysiology of neuropsychiatric disorders. The impact of repetitive transcranial magnetic stimulation (rTMS) on NMDAR-related amino acids remains unknown. We aim to investigate the effects of rTMS on NMDAR-related amino acids in serum of post-stroke patients. METHODS: Ninety-five consecutive post-stroke patients with upper limb hemiparesis were recruited. In 27 patients, the Beck Depression Inventory (BDI) score was 10 or higher. Twelve depressed patients underwent rehabilitation in combination with rTMS and 15 non-depressed patients underwent rehabilitation only without rTMS for 14 days. 1 Hz rTMS was applied to the primary motor area in the non-lesional hemisphere. BDI was conducted before and after treatment. Serum glutamine, glutamate, glycine, L-serine, and D-serine levels were measured before and after treatment. RESULTS: There were no differences between depressed patients and non-depressed patients in clinical characteristics, levels of the five amino acids in serum, and the ratio of amino acids. However, in 27 depressed patients there was a significant correlation between levels of glutamate in serum and BDI (ρ=0.428、p=0.026). BDI decreased significantly in depressed patients after treatment with or without rTMS. D-serine decreased in the rehabilitation with rTMS group, but increased in the rehabilitation without rTMS group. L-serine increased in the rehabilitation with rTMS group, but decreased in the rehabilitation without rTMS group. CONCLUSIONS: The results suggest that rTMS can modulate NMDAR-related amino acids in blood, producing beneficial effects.

Comparative assessment of sarcopenia using the JSH, AWGS, and EWGSOP2 criteria and the relationship between sarcopenia, osteoporosis, and osteosarcopenia in patients with liver cirrhosis.

BACKGROUND: Sarcopenia and osteoporosis reduce life quality and worsen prognosis in patients with liver cirrhosis (LC). When these two complications coexist, a diagnosis of osteosarcopenia is made. We aimed to investigate the actual situations of sarcopenia, osteoporosis, osteosarcopenia, and vertebral fracture, and to clarify the relationship among these events in patients with LC. METHODS: We describe a cross-sectional study of 142 patients with LC. Sarcopenia was defined according to the Japan Society of Hepatology (JSH) criteria, Asian Working Group for Sarcopenia (AWGS) criteria, and European Working Group on Sarcopenia in Older People (EWGSOP2) criteria. The skeletal muscle mass index (SMI) and handgrip strength were assessed using bioelectrical impedance analysis and a digital grip strength dynamometer, respectively. Bone mineral density (BMD) was measured using dual energy X-ray absorptiometry, and vertebral fracture was evaluated using spinal lateral X-rays. The severity of LC was assessed using the Child-Pugh classification. RESULTS: Among the 142 patients, the prevalence of sarcopenia was 33.8% (48/142) according to the JSH and AWGS criteria and 28.2% (40/142) according to the EWGSOP2 criteria. The number of patients with osteoporosis, osteosarcopenia, and vertebral fracture was 49 (34.5%), 31 (21.8%), and 41 (28.9%), respectively. Multivariate analysis revealed a close association between sarcopenia and osteoporosis. Osteoporosis was independently associated with sarcopenia [odds ratio (OR) = 3.923, P = 0.010]. Conversely, sarcopenia was independently associated with osteoporosis (OR = 5.722, P < 0.001). Vertebral fracture occurred most frequently in patients with osteosarcopenia (19/31; 61.3%) and least frequently in those without both sarcopenia and osteoporosis (12/76; 15.8%). The SMI and handgrip strength values were significantly correlated with the BMD of the lumbar spine (r = 0.55 and 0.51, respectively; P < 0.001 for both), femoral neck, (r = 0.67 and 0.62, respectively; P < 0.001 for both), and total hip (r = 0.67 and 0.61, respectively; P < 0.001 for both). CONCLUSIONS: Sarcopenia, osteoporosis, osteosarcopenia, and vertebral fracture were highly prevalent and closely associated with one another in patients with LC. Specifically, patients with osteosarcopenia had the highest risk of vertebral fractures. Early diagnosis of these complications is essential for treatment intervention.

Effect of baseline brain activity on response to low-frequency rTMS/intensive occupational therapy in poststroke patients with upper limb hemiparesis: a near-infrared spectroscopy study.

BACKGROUND: The beneficial effects of the combination therapy of low-frequency repetitive transcranial magnetic stimulation of nonlesional hemisphere and intensive occupational therapy (LF-rTMS/OT) on upper limb hemiparesis have been well established in poststroke patients. However, there is no information on the effect of brain activity on LF-rTMS/OT treatment outcome. METHOD: A total of 59 poststroke patients with upper limb hemiparesis received 15-day LF-rTMS/OT. Motor function of the affected upper limb was evaluated before and after the treatment. We also conducted functional near-infrared spectroscopy (fNIRS) before the treatment and calculated the laterality index (LI) based on the change in oxy-hemoglobin in the primary sensorimotor cortex and supplementary motor cortex. The correlation between LI before LF-rTMS/OT and observed improvement in upper limb motor function was analyzed. RESULTS: Motor recovery was significantly more pronounced in patients with unaffected hemisphere dominance in both hemispheres (LI of -1 to 0) than in those with affected hemisphere dominance in the lesional hemisphere (LI of 0 to 1). There was a significant negative correlation between LI and improvement in upper limb motor function. DISCUSSION: The results demonstrated that patients with a shift in brain activity to the noninjured cerebral cortex exhibited better motor recovery following LF-rTMS/OT. The findings suggest that evaluation of brain asymmetry before LF-rTMS/OT with fNIRS can help predict the response to LF-rTMS/OT.

Isotopically-Labeled Iodoacetamide-Alkyne Probes for Quantitative Cysteine-Reactivity Profiling.

Cysteine residues on proteins serve a variety of catalytic and regulatory functions due to the high nucleophilicity and redox activity of the thiol group. Quantitative proteomic platforms for profiling cysteine reactivity can provide valuable information related to the post-translational modification state and inhibitor occupancy of functional cysteine residues within a complex proteome. Cysteine-reactivity profiling typically monitors changes in the extent of cysteine labeling by cysteine-reactive chemical probes, such as iodoacetamide (IA)-alkyne. To enable accurate measurements of cysteine reactivity changes, isotopic labels are introduced into the two proteomes of interest using either isotopically tagged proteomes (SILAC) or cleavable linkers (isoTOP-ABPP) that are installed using copper-catalyzed azide-alkyne cycloaddition (CuAAC). Here we provide an alternative strategy for isotopic tagging of two proteomes for cysteine-reactivity profiling by developing IA-light and IA-heavy, a pair of isotopically labeled iodoacetamide-alkyne probes. These probes can be utilized for proteome samples that are not amenable to SILAC labeling and are facile to synthesize, especially when compared to the isotopically tagged cleavable linkers. We confirm the quantitative accuracy of IA-light and IA-heavy by assessing cysteine reactivity in a purified thioredoxin protein, as well as globally within a complex proteome where IA-light treatment generates mass-spectrometry identification of 992 cysteine residues. Importantly, these isotopically tagged probes can also be utilized for quantifying the percentage of cysteine modification within a single sample. Preliminary data supports the use of these tags to quantify the stoichiometry of TCEP-susceptible cysteine oxidation events in cell lysates.

Beneficial Effect of Intradialytic Electrical Muscle Stimulation in Hemodialysis Patients: A Randomized Controlled Trial.

Many hemodialysis (HD) patients cannot perform self-administered exercise training for their muscle wasting, weakness, and sarcopenia. Electrical muscle stimulation (EMS) has the advantages of easy application, and minimal risks for these patients. This study aimed to evaluate the effects of intradialytic EMS. This was a prospective, open-label, randomized controlled trial. Twenty-nine HD patients were randomly assigned to either the EMS group or the control (no training) group, and 13 patients in each group were eventually analyzed. The EMS group received intradialytic EMS over an 8-week period. Measurement of isometric knee extensor strength using a handheld dynamometer, evaluation of the quadriceps cross-sectional area (CSA) using magnetic resonance imaging (MRI), the Timed Up & Go Test (TUG) for physical function assessment, the Japanese version of the Short Form-8 Health Survey (SF-8), and blood tests were performed before and after the intervention period. The primary and secondary outcomes were improvement of quadriceps muscle strength and size, respectively. The EMS group demonstrated significant improvement compared with the control group in terms of knee extensor strength (right: 22.3 ± 12.8 vs. -10.8 ± 22.3 N, P < 0.001; left: 26.1 ± 29.7 vs. -8.3 ± 18.7 N, P < 0.001), quadriceps CSA at three positions, 25, 50, and 75% of the segment length from the greater trochanter to the inferior border of the lateral epicondyle of the femur (25% right: EMS group 1.7 ± 2.0 vs. Control group -0.4 ± 1.8cm2 , P = 0.05; 25% left: EMS group 1.3 ± 1.1 vs. Control group -0.6 ± 1.8cm2 , P = 0.01; 50% right: EMS group 2.0 ± 2.2 vs. Control group -0.7 ± 1.9cm2 , P = 0.004; 50% left: EMS group 2.7 ± 2.1 vs. Control group -0.7 ± 1.6cm2 , P = 0.001; 75% right: EMS group 1.8 ± 2.2 vs. Control group -0.7 ± 1.5cm2 , P = 0.003; 75% left: EMS group 2.1 ± 1.9 vs. Control group -0.4 ± 1.5cm2 , P = 0.003); and TUG time (-0.8 ± 0.6 vs. 0.2 ± 0.5s, P < 0.001). The EMS group showed improvement after intervention in all components of SF-8, but these were not statistically significant. EMS could be an effective exercise training tool for HD patients with either muscle wasting, weakness, or sarcopenia.

Impact of orthotic therapy for improving activities of daily living in individuals with spinal cord injury: a retrospective cohort study.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To determine the impact of leg orthotic therapy for improving activities of daily living after spinal cord injury. SETTING: Participating acute care and rehabilitation hospitals across Japan. METHODS: We retrospectively identified individuals with spinal cord injury admitted to eight participating hospitals in 2015-2016 from the Japan Rehabilitation Database. Data for 293 individuals were analyzed. Propensity score analysis by inverse probability weighting (IPW) was applied to adjust for potential bias and create two comparable groups. Outcomes were compared between the leg orthotic group and the non-leg orthotic group, using IPW. The primary outcome was motor Functional Independence Measure® (FIM) effectiveness score and the secondary outcome was motor FIM score at discharge. FIM was measured on hospital admission and discharge. RESULTS: Leg orthoses were prescribed for 26% of the 293 individuals. Those prescribed leg orthoses had significantly higher motor FIM effectiveness scores than those who were not, before and after IPW (motor FIM effectiveness: 0.54 vs. 0.35, p < 0.01 and 0.45 vs. 0.36, p = 0.02). Discharge motor FIM was significantly higher in individuals who were prescribed leg orthoses than in those who were not, before and after IPW (discharge motor FIM: 64.5 vs. 52.2, p < 0.01 and 58.9 vs. 53.5, p = 0.02). CONCLUSIONS: Leg orthoses may improve activities of daily living in individuals with spinal cord injury after the acute phase.

Diffusion Tensor Imaging Evaluation of Neural Network Development in Patients Undergoing Therapeutic Repetitive Transcranial Magnetic Stimulation following Stroke.

We aimed to investigate plastic changes in cerebral white matter structures using diffusion tensor imaging following a 15-day stroke rehabilitation program. We compared the detection of cerebral plasticity between generalized fractional anisotropy (GFA), a novel tool for investigating white matter structures, and fractional anisotropy (FA). Low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) of 2400 pulses applied to the nonlesional hemisphere and 240 min intensive occupation therapy (OT) daily over 15 days. Motor function was evaluated using the Fugl-Meyer assessment (FMA) and Wolf Motor Function Test (WMFT). Patients underwent diffusion tensor magnetic resonance imaging (MRI) on admission and discharge, from which bilateral FA and GFA values in Brodmann area (BA) 4 and BA6 were calculated. Motor function improved following treatment (p < 0.001). Treatment increased GFA values for both the lesioned and nonlesioned BA4 (p < 0.05, p < 0.001, resp.). Changes in GFA value for BA4 of the lesioned hemisphere were significantly inversely correlated with changes in WMFT scores (R2 = 0.363, p < 0.05). Our findings indicate that the GFA may have a potentially more useful ability than FA to detect changes in white matter structures in areas of fiber intersection for any such future investigations.

Relationship Between Frequency of Spontaneous Swallowing and Salivary Substance P Level in Patients with Acute Stroke.

The frequency of spontaneous swallowing is useful for screening of dysphagia in acute stroke. Low levels of substance P (SP) in saliva attenuate the swallowing reflex. The aim of this study was to determine the relationship between the frequency of spontaneous swallowing and salivary SP levels. In 40 subjects, saliva was collected within 72 h after stroke onset and salivary SP levels were measured using ELISA kit at a later date. The frequency of spontaneous swallowing was measured over 1 h using a microphone placed on the neck. Pneumonia was diagnosed by the presence of pyrexia and at least two respiratory problems of four categories (sputum, cough or breathing pattern, breath sound, and gas change). The presence of detectable levels of SP in the saliva was confirmed in 17 patients (high SP group), whereas the level was below the detection limit of the ELISA kit in 23 patients (low SP group). The frequency of spontaneous swallowing was significantly lower in low SP group (16.1 ± 11.6 per hour) than in the high SP group (30.4 ± 20.4, p = 0.016). As the result of multiple regression analysis, salivary SP levels were correlated with frequency of spontaneous swallowing independently of age, NIHSS, and GCS. The incidence of pneumonia was significantly higher in the low than high SP group (p < 0.001). In conclusion, the frequency of spontaneous swallowing was decreased in acute stroke patients with low salivary SP levels. Salivary SP levels can be potentially a useful biomarker of risk of stroke-associated pneumonia in the acute stage.

Effects of botulinum toxin A therapy and multidisciplinary rehabilitation on lower limb spasticity classified by spastic muscle echo intensity in post-stroke patients.

OBJECTIVES: The purpose of the present study was to investigate retrospectively the relationship between botulinum toxin type A plus multidisciplinary rehabilitation and muscle echo intensity in post-stroke patients with spasticity. The primary aim was to investigate whether the effects of the intervention on the improvement of spasticity depend on muscle echo intensity, and the secondary aim was to investigate whether the motor function of the lower limbs depends on muscle echo intensity. METHODS: A 12-day inpatient protocol was designed for 102 post-stroke patients with spasticity due to lower limb paralysis. Muscle echo intensity of the triceps surae muscle was measured by ultrasonography, and the patients were categorized into four groups based on Heckmatt scale grades (Grades I-IV). RESULTS: All four groups classified by the Heckmatt scale showed significant pre-to-post-intervention differences in the knee and ankle modified Ashworth scale scores (p < 0.05). Grades I-III patient groups showed a significant improvement in lower limb motor function following intervention. Grade IV patients did not show a significant improvement in lower limb motor function. CONCLUSIONS: We observed significant improvements in the modified Ashworth scale scores after botulinum toxin type A and multidisciplinary rehabilitation therapy on post-stroke patients with spasticity. Although patients with lower muscle echo intensity demonstrated improvements in motor function, the improvement was poor in those with higher muscle echo intensity.