Validity of the Functional Classification of the Upper Extremities for Duchenne Muscular Dystrophy.

Objectives: Some upper-limb function assessments can evaluate treatments in the non-ambulatory stage of Duchenne muscular dystrophy (DMD). The Functional Classification of the Upper Extremities (FCUE) was developed for DMD in Japan. The FCUE is easier to use than the Performance of Upper Limb (PUL) and is more detailed than the Brooke Upper Extremity Scale. This study aimed to determine the concurrent validity of FCUE with other methods of assessment for DMD. Methods: This retrospective study reviewed the medical records of 39 boys with DMD from the National Center of Neurology and Psychiatry to evaluate the concurrent validity of the FCUE and PUL using non-parametric Spearman rank correlation (ρ). We also determined the concurrent validity of the Brooke Upper Extremity Scale and PUL for comparison. Results: The ρ value between the FCUE and PUL was -0.914 (P<0.001). The FCUE showed robust concurrent validity with the PUL. That correlation between the FCUE and Brooke Upper Extremity Scale gave a ρ value of -0.854 (P<0.001). Conclusions: The FCUE had a higher concurrent validity with the PUL than with the Brooke Upper Extremity Scale. The FCUE is considered a valid assessment tool of upper-limb function in boys with DMD. Selecting the best assessment method depends on the severity of the patient's condition and a balance between assessment accuracy and evaluation time.

Structural Validity of the Mini-Balance Evaluation Systems Test in Individuals With Spinocerebellar Ataxia: A Rasch Analysis Study.

OBJECTIVE: To examine the structural validity of the Mini-Balance Evaluation Systems Test (Mini-BESTest) in individuals with spinocerebellar ataxia (SCA). DESIGN: Methodological research on data gathered in a cross-sectional study. A Rasch analysis was conducted (partial credit model). SETTING: Inpatients in a hospital rehabilitation setting. PARTICIPANTS: A pooled sample of patients with SCA (N=65 [total 110 data]; 23 women, 42 men; mean±SD age 63.1±9.9y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: We evaluated the Mini-BESTest's category structure, unidimensionality, and measurement accuracy (0: unable to perform or requiring help to 2: normal performance). RESULTS: The Mini-BESTest rating scale fulfilled the category functioning criteria. The analysis of the standardized Rasch residuals showed the scale's unidimensionality, but there were 7 item pairs indicating local dependence. All of the items fit the underlying scale construct (dynamic balance), with the exception of item #1, "Sit to stand," which was an underfit. The Mini-BESTest demonstrated adequate reliability (person separation reliability=.87) and separated the patients into 5 strata. The item-difficulty measures ranged from -4.49 to 2.02 logits, and the person ability-item difficulty matching was very good (the mean of person ability=-.07 logits and the mean of item difficulty=.00). No floor or ceiling effects were detected. The keyform identified items with small (#11, "Walk with head turns, horizontal") and large (#3, "Stand on 1 leg") item thresholds. CONCLUSIONS: The Mini-BESTest has a unidimensional balance assessment scale with good category structure and reliability even for individuals with SCA. However, it also has some inherent shortcomings such as fit statistics, local item dependencies, and item thresholds. The results obtained when the Mini-BESTest is administered to patients with cerebellar ataxia should, thus, be interpreted cautiously.

Repetitive transcranial magnetic stimulation for apathy in patients with neurodegenerative conditions, cognitive impairment, stroke, and traumatic brain injury: a systematic review.

Background: We aimed to determine the effects and tolerability of repetitive transcranial magnetic stimulation (rTMS) on apathy in patients with neurodegenerative conditions, mild cognitive impairment (MCI), stroke, and traumatic brain injury (TBI) via systematic review. Methods: We conducted a systematic search in major electronic health databases, including PubMed, Scopus, and PsycINFO, covering the period from inception to June 2023. Comparative clinical trials and cohort studies, and studies with before-after designs were considered for inclusion. We used the Cochrane Risk of Bias and the National Institutes of Health (NIH) tools to assess methodological quality. Results: Out of 258 records identified, 14 studies met our eligibility criteria (11 randomized controlled trials (RCT) and 3 studies utilized before-and-after designs) with a total of 418 patients (overall female-to-male ratio 1:1.17) included in the review. The overall methodological quality of the included studies was assessed to be fair to good. The stimulation parameters used varied considerably across the studies. The summary findings of our review indicate the following observations on the effects of rTMS on apathy: (1) the results of all included studies in Alzheimer's disease investigating the effects of rTMS on apathy have consistently shown a positive impact on apathy; (2) the majority of studies conducted in Parkinson's disease have not found statistically significant results; (3) a single study (RCT) on patients with primary progressive aphasia demonstrated significant beneficial effects of rTMS on apathy; (4) the trials conducted on individuals with MCI yielded varying conclusions; (5) one study (RCT) in chronic stroke suggested that rTMS might have the potential to improve apathy; (6) one study conducted on individuals with mild TBI did not find a significant favorable association on apathy; and (7) the use of different rTMS protocols on the populations described is generally safe. Conclusion: The feasibility of utilizing rTMS as a treatment for apathy has been suggested in this review. Overall, limited evidence suggests that rTMS intervention may have the potential to modify apathy among patients with AD, PPA, MCI and chronic stroke, but less so in PD and mild TBI. These findings require confirmation by larger, well-designed clinical trials.

Treatment outcome of local injection of botulinum toxin for claw toe: Differences between cerebral hemorrhage and infarction.

BACKGROUND: Some patients with post-stroke claw toe respond well to botulinum toxin (BoNT) treatment while others do not. This study was designed to assess the impact of stroke type (cerebral hemorrhage and cerebral infarction) on the outcome of BoNT treatment for claw toe. METHODS: We retrospectively examined the medical records of patients who received local BoNT (onabotulinumtoxin A) injections into the flexor hallucis longus (FHL) and flexor digitorum longus (FDL) muscles. All patients suffered stroke-related leg paralysis and spasticity. RESULTS: The study participants were 58 patients (mean age, 61.4 ± 10.3 years, ± SD) with time since stroke of 6.7 ± 4.4 years. The stroke type was cerebral hemorrhage (n = 38) and cerebral infarction (n = 20). After a total of 124 BoNT administrations with medical records entries on the subjective symptoms, the odds for symptomatic improvement was approximately 5.8 times higher in patients of the infarction group compared with the hemorrhage group (OR = 5.787, 95% CI = 2.369-14.134, p = 0. 000). Fifty-one patients (32 with cerebral hemorrhage, 19 with cerebral infarction) received the first local BoNT injection and had available medical records, analysis of which showed a significantly higher rate of symptomatic improvement in patients of the infarction group than those of the hemorrhage group (p = 0.006). After adjustment by factors known to influence treatment outcome (degree of spasticity and paralysis, BoNT dosage, and extent of FDL muscle control of toe movements), the treatment effect was predominantly higher in patients with cerebral infarction. CONCLUSION: The BoNT treatment response was better for claw toes in cerebral infarction patients than in hemorrhage patients, possibly suggesting that claw toe is associated with more severe spasticity in this group of patients.

Effects of Flexor Digitorum Longus Muscle Anatomical Structure on the Response to Botulinum Toxin Treatment in Patients with Post-Stroke Claw Foot Deformity.

(1) Background: The purpose of this retrospective case-control study was to determine the relationship between the control of toe movements by flexor hallucis longus (FHL) and flexor digitorum longus (FDL) muscles and the response to treatment with botulinum toxin (BoNT) in post-stroke patients with claw toe. (2) Methods: Subjects with stroke-related leg paralysis/spasticity and claw toes received multiple injections of BoNT (onabotulinumtoxin A) into the FHL or FDL muscles. We investigated the relationship between the mode of transmission of FHL and FDL muscle tension to each toe (MCT) and treatment outcome using the data of 53 patients who received 124 injections with clinically recorded treatment outcome. We also dissected the potential variables that could determine the treatment outcome. (3) Results: The effectiveness of BoNT treatment was significantly altered by FDL-MCT (OR = 0.400, 95% CI = 0.162-0.987, p = 0.047). Analysis of the response to the first BoNT injection showed an odds ratio of FDL-MCT of approximately 6.0 times (OR = 0.168, 95% CI = 0.033-0.857, p = 0.032). The more tibial the influence of the FDL muscle on each toe, the better the treatment outcome on the claw toe. (4) Conclusions: The anatomic relation between FDL muscle and each toe seems to affect the response to treatment with BoNT in post-stroke patients with claw toes.

Comparison of the effect and treatment sequence between a 2-week parallel repetitive transcranial magnetic stimulation and rehabilitation and a 2-week rehabilitation-only intervention during a 4-week hospitalization for upper limb paralysis after stroke: An open-label, crossover observational study.

BACKGROUND: NEURO® is a 2-week program that combines low-frequency repetitive transcranial magnetic stimulation (rTMS) and intensive occupational therapy (OT) to treat patients with chronic hemiparesis following stroke. The degree to which each element contributes to the improvement of upper limb function remains unclear. It has been suggested that low-frequency rTMS applied to a healthy cerebrum activates neural activity in the contralateral hemispheric area surrounding the lesion. Intensive OT performed in parallel to rTMS promotes the functional remodeling of the cerebrum to help with rehabilitation. OBJECTIVES: However, this has not been demonstrated using NEURO®. Therefore, we aimed to compare the effects of the NEURO® and OT-only protocols in patients with hemiparesis following stroke. METHODS: Thirty-seven patients with upper limb paralysis following stroke were recruited and hospitalized for treatments and randomly divided into two groups. Group A consisted of 16 patients who underwent NEURO® for the first 2 weeks, and Group B consisted of 21 patients who underwent OT-only for the first 2 weeks. After 2 weeks of hospitalization, the treatments of Groups A and B were reversed for the subsequent 2 weeks of treatment. Improvement in upper limb motor function in Groups A and B at 2 and 4 weeks after the start of treatment was evaluated using the Fugl-Meyer Motor Assessment (FMA) and the Wolf Motor Function Test (WMFT). RESULTS: Group A, who underwent NEURO® first during their initial 2-week hospitalization, showed significantly greater improvement than that in Group B, who underwent OT-only first (P = .041 for FMA and P < .01 for WMFT). At 4 weeks following the reversal of treatments, Group A who underwent NEURO® and then OT-only showed significantly greater improvement than that in Group B, who underwent OT-only followed by NEURO® (P = .011 for FMA and P = .001 for WMFT). CONCLUSION: Our findings indicate that rTMS facilitates neuromodulation when combined with OT, which leads to more effective rehabilitation than with OT alone (Trial registration: JMACCT (http://www.jmacct.med.or.jp/); trial ID JMA-IIA00215).

Prognosis prediction of the effect of botulinum toxin therapy and intensive rehabilitation on the upper arm function in post-stroke patients using hierarchical cluster analysis.

PURPOSE: We analysed the effect of botulinum neurotoxin A therapy (BoNT-A) with intensive rehabilitation on the upper limb (UL) spasticity in post-stroke patients by classifying function by UL movement and examining differences in functional improvement. MATERIALS AND METHODS: In this non-randomized, controlled study. The patient function was classified into groups from the score of the sub-categories of the Fugl-Meyer Assessment (FMA-UE) before treatment in the Intervention group by hierarchical cluster analysis. RESULTS: A total of 139 patients in the Intervention group were classified into six groups. All groups showed a significant improvement in FMA-UE after the intervention. In the group scoring 19-31 points on the FMA-UE and with the voluntary movement of shoulder, elbow, forearm, and finger, a significant improvement was observed compared to the Control group. Further, in the group scoring 26-47 points on the FMA-UE and with the voluntary movement of shoulder, elbow, forearm, wrist, and finger, a significant improvement was observed compared to the Control group. CONCLUSIONS: In this study, BoNT-A and intensive rehabilitation showed improvement in spasticity and UL function. A high therapeutic effect is expected in patients with moderate impairment levels who have voluntary movement in whole UL or in UL except for the wrist.IMPLICATIONS FOR REHABILITATIONHierarchical cluster analysis focusing on the Fugl-Meyer Assessment of the Upper Extremity sub-categories may be useful for studies aimed to improve the upper arm function.Botulinum Neurotoxin A therapy (BoNT-A) and intensive rehabilitation in post-stroke patients showed improvement in spasticity and upper arm function.The degree of the upper arm function before the intervention may affect the improvement effect of BoNT-A and intensive rehabilitation.In the motor function, the post-stroke patients with a moderate impairment level who have voluntary movement of the whole upper limb or upper limb except for the wrist are most likely to receive these therapeutic effects.

Shear Wave Velocity to Evaluate the Effect of Botulinum Toxin on Post-Stroke Spasticity of the Lower Limb.

(1) Background: The evaluation of muscles with spasticity using ultrasound elastography has attracted attention recently, and the shear wave velocity (SWV) technique can measure the mechanical properties of tissues objectively and quantitatively. The purpose of this study was to evaluate the effect of using SWV to assess the effect of Botulinum toxin type A (BoNT-A) treatment in adult patients with post-stroke lower limb spasticity. (2) Methods: We assessed the modified Ashworth Scale, the modified Tardieu Scale, and SWV at rest and after stretching before and at 1 month after BoNT-A treatment in 10 adult participants with post-stroke lower limb spasticity. (3) Results: Significant changes in SWV of the ankle joint in maximum dorsiflexion to the extent possible (SWV stretched) were observed after BoNT-A treatment. SWV stretched was positively correlated with joint range of motion. Participants whose joint range of motion did not improve (i.e., gastrocnemius medialis muscle (GCM) extension distance did not change) had significantly more reductions in SWV stretched after BoNT-A treatment. (4) Conclusions: Our results suggest that the SWV measurements may serve as a quantitative assessment to determine the effect of the BoNT-A treatment in adult stroke patients. SWV measurements to assess GCM spasticity should consider the effects of tension, material properties and activation level of muscles. The challenge is to measure SWV with matching limb positions in patients without contractures.

New Treatment Strategy Using Repetitive Transcranial Magnetic Stimulation for Post-Stroke Aphasia.

Repetitive transcranial magnetic stimulation (rTMS) for post-stroke aphasia (PSA) has been suggested to promote improvement of language function when used in combination with rehabilitation. However, many challenges remain. In some reports examined by category of language function, only naming has good evidence of improvement, and the improvement effect on other language modalities is low. Therefore, it is necessary to establish methods that contribute to the improvement of language functions other than naming. Therapeutic methods for PSA based on the mechanism of rTMS are mainly inhibitory stimulation methods for language homologous areas. However, the mechanisms of these methods are controversial when inferred from the process of recovery of language function. Low-frequency rTMS applied to the right hemisphere has been shown to be effective in the chronic phase of PSA, but recent studies of the recovery process of language function indicate that this method is unclear. Therefore, it has been suggested that evaluating brain activity using neuroimaging contributes to confirming the effect of rTMS on PSA and the elucidation of the mechanism of functional improvement. In addition, neuroimaging-based stimulation methods (imaging-based rTMS) may lead to further improvements in language function. Few studies have examined neuroimaging and imaging-based rTMS in PSA, and further research is required. In addition, the stimulation site and stimulation parameters of rTMS are likely to depend on the time from onset to intervention. However, there are no reports of studies in patients between 90 and 180 days after onset. Therefore, research during this period is required. New stimulation methods, such as multiple target methods and the latest neuroimaging methods, may contribute to the establishment of new knowledge and new treatment methods in this field.

The Effect of Non-Invasive Brain Stimulation (NIBS) on Executive Functioning, Attention and Memory in Rehabilitation Patients with Traumatic Brain Injury: A Systematic Review.

In recent years, the potential of non-invasive brain stimulation (NIBS) for therapeutic effects on cognitive functions has been explored for populations with traumatic brain injury (TBI). However, there is no systematic NIBS review of TBI cognitive impairment with a focus on stimulation sites and stimulation parameters. The purpose of this study was to conduct a systematic review examining the effectiveness and safety of NIBS for cognitive impairment after a TBI. This study was prospectively registered with the PROSPERO database of systematic reviews (CRD42020183298). All English articles from the following databases were searched from inception up to 31 December 2020: Pubmed/MEDLINE, Scopus, CINAHL, Embase, PsycINFO and CENTRAL. Randomized and prospective controlled trials, including cross-over studies, were included for analysis. Studies with at least five individuals with TBI, whereby at least five sessions of NIBS were provided and used standardized neuropsychological measurement of cognition, were included. A total of five studies met eligibility criteria. Two studies used repetitive transcranial magnetic stimulation (rTMS) and three studies used transcranial direct current stimulation (tDCS). The pooled sample size was 44 individuals for rTMS and 91 for tDCS. Three of five studies combined cognitive training or additional therapy (computer assisted) with NIBS. Regarding rTMS, target symptoms included attention (n = 2), memory (n = 1), and executive function (n = 2); only one study showing significant improvement compared than control group with respect to attention. In tDCS studies, target symptoms included cognition (n = 2), attention (n = 3), memory (n = 3), working memory (WM) (n = 3), and executive function (n = 1); two of three studies showed significant improvement compared to the control group with respect to attention and memory. The evidence for NIBS effectiveness in rehabilitation of cognitive function in TBI is still in its infancy, more studies are needed. In all studies, dorsolateral prefrontal cortex (DLPFC) was selected as the stimulation site, along with the stimulation pattern promoting the activation of the left DLPFC. In some studies, there was a significant improvement compared to the control group, but neither rTMS nor tDCS had sufficient evidence of effectiveness. To the establishment of evidence we need the evaluation of brain activity at the stimulation site and related areas using neuroimaging on how NIBS acts on the neural network.

The Effect of Non-Invasive Brain Stimulation (NIBS) on Attention and Memory Function in Stroke Rehabilitation Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: In recent years, the potential of non-invasive brain stimulation (NIBS) for therapeutic effects on cognitive functions has been explored for populations with stroke. There are various NIBS methods depending on the stimulation site and stimulation parameters. However, there is no systematic NIBS review of post-stroke cognitive impairment with a focus on stimulation sites and stimulation parameters. The purpose of this study is to conduct a systematic review and meta-analysis on effectiveness and safety of NIBS for cognitive impairment after a stroke to obtain new insights. This study was prospectively registered with the PROSPERO database of systematic reviews (CRD42020183298). METHODS: All English articles from MEDLINE, Scopus, CINAHL, Embase, PsycINFO, and CENTRAL were searched from inception up to 31 December 2020. Randomized and prospective controlled trials were included for the analysis. Studies with at least five individuals post-stroke, whereby at least five sessions of NIBS were provided and using standardized neuropsychological measurement of cognition, were included. We assessed the methodological quality of selected studies as described in the Physiotherapy Evidence Database (PEDro) scoring system. RESULTS: A total of 10 studies met eligibility criteria. Six studies used repetitive transcranial magnetic stimulation (rTMS) and four studies used transcranial direct current stimulation (tDCS). The pooled sample size was 221 and 196 individuals who received rTMS and tDCS respectively. Eight studies combined general rehabilitation, cognitive training, or additional therapy with NIBS. In rTMS studies, target symptoms included global cognition (n = 4), attention (n = 3), memory (n = 4), working memory (WM) (n = 3), and executive function (n = 2). Five studies selected the left dorsolateral prefrontal cortex (DPLFC) as the stimulation target. One rTMS study selected the right DLPFC as the inhibitory stimulation target. Four of six studies showed significant improvement. In tDCS studies, target symptoms included global cognition (n = 2), attention (n = 4), memory (n = 2) and WM (n = 2). Three studies selected the frontal area as the stimulation target. All studies showed significant improvement. In the meta-analysis, rTMS showed a significant effect on attention, memory, WM and global cognition classified by neuropsychological tests. On the other hand, tDCS had no significant effect. CONCLUSIONS: In post-stroke patients with deficits in cognitive function, including attention, memory, and WM, NIBS shows promising positive effects. However, this effect is limited, suggesting that further studies are needed with more precision in stimulation sites and stimulation parameters. Future studies using advanced neurophysiological and neuroimaging tools to allow for a network-based approach to treat cognitive symptoms post-stroke with NIBS are warranted.

Effect of repetitive transcranial magnetic stimulation on the kynurenine pathway in stroke patients.

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) improves depressive symptoms and motor function in stroke patients. While metabolic derangement of the kynurenine pathway has been reported in stroke patients, the effect of rTMS on this pathway remains unknown. This study was performed to investigate the effect of rTMS on serum levels of kynurenine and tryptophan in stroke patients. METHODS: Sixty-two stroke patients received rTMS in addition to intensive rehabilitation and 33 stroke patients received intensive rehabilitation alone for 14 days. The rTMS involved low-frequency stimulation (at 1 Hz) of the primary motor cortex on the unaffected side of the cerebrum. The depressive state of the patients was evaluated with the Beck Depression Inventory (BDI) before and after treatment. Motor function of the patients was evaluated with Fugl-Meyer Assessment (FMA). Serum levels of kynurenine and tryptophan levels were also measured before and after treatment. RESULTS: The serum tryptophan level decreased in the group receiving rTMS to the right brain and increased in the group receiving rTMS to the left brain. The serum kynurenine/tryptophan ratio was elevated in the group receiving rTMS to the right brain. The BDI indicated improvement of depressive symptoms in the rehabilitation alone group and the group receiving rTMS to the right brain plus rehabilitation. The FMA improved in all groups. CONCLUSIONS: The effect of low-frequency rTMS on the kynurenine pathway may differ depending on whether it is applied to the right or left cerebral hemisphere.

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.

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.

Botulinum Toxin Therapy Combined with Rehabilitation for Stroke: A Systematic Review of Effect on Motor Function.

AIM: The purpose of this study was to examine the effectiveness of botulinum toxin A (BoNT-A) therapy combined with rehabilitation on motor function in post-stroke patients. METHODS: The following sources up to December 31, 2018, were searched from inception for articles in English: Pubmed, Scopus, CINAHL, Embase, PsycINFO, and CENTRAL. Trials using injections of BoNT-A for upper and lower limb rehabilitation were examined. We excluded studies that were not performed for rehabilitation or were not evaluated for motor function. RESULTS: Twenty-six studies were included. In addition to rehabilitation, nine studies used adjuvant treatment to improve spasticity or improve motor function. In the upper limbs, two of 14 articles indicated that significant improvement in upper limb motor function was observed compared to the control group. In the lower limbs, seven of 14 articles indicated that significant improvement in lower limb motor function was observed compared to the control group. CONCLUSIONS: The effect of combined with rehabilitation is limited after stroke, and there is not sufficient evidence, but results suggest that BoNT-A may help to improve motor function. In future studies, the establishment of optimal rehabilitation and evaluation times of BoNT-A treatment will be necessary for improving motor function and spasticity.

The Effect of Repeated Botulinum Toxin A Therapy Combined with Intensive Rehabilitation on Lower Limb Spasticity in Post-Stroke Patients.

OBJECTIVES: This study is a retrospective investigation of the effects of repetitive botulinum toxin A therapy (BoNT-A) and intensive rehabilitation (IR) on lower limb spasticity in post-stroke patients. METHODS: Thirty-five post-stroke patients was included in this study and received BoNT-A for the first time. A 12-day inpatient protocol was with 4 cycles of the treatment protocol. The severity of spasticity, motor function and brace status were evaluated. RESULTS: The modified Ashworth Scale (MAS) score of ankle dorsiflexors, range of motion, walking speed and balancing ability were significantly improved after cycle 1. The improvement of spasticity and motor function was persistent through cycles 2⁻4. One-third of brace users were able to discontinue the use of a brace. All of these brace users showed a forward gait pattern prior to therapy. CONCLUSIONS: Repeated BoNT-A combined with IR improved lower limb spasticity in post-stroke patients. Our results suggest that patients who show the forward gait pattern prior to therapy may be able to discontinue the use of their brace after therapy.

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.

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.

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.