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.

White matter degeneration in diffuse axonal injury and mild traumatic brain injury observed with automatic tractography.

A better understanding of white matter tract damage in patients with diffuse axonal injury (DAI) and mild traumatic brain injury (MTBI) is important to obtain an objective basis for sequelae. The purpose of this study was to clarify the characteristics of white matter tract degeneration in DAI and MTBI using automated tractography. T1-weighted and diffusion tensor imaging (DTI) was performed on seven DAI and seven MTBI patients as well as on nine healthy subjects. Automated probabilistic tractography analysis was performed using FreeSurfer and TRACULA (tracts constrained by underlying anatomy) for the reconstruction of major nerve fibers. We investigated the difference between DTI quantitative values in each white matter nerve fiber between groups and attempted to evaluate the classification accuracy of DAI and MTBI using receiver operator curve analysis. Both DAI and MTBI appeared to exhibit axonal degeneration along the nerve fiber tract in a scattered manner. The mean diffusivity of the ampulla of the corpus callosum was significantly higher in DAI than that in MTBI patients, suggesting axonal degeneration of the corpus callosum in DAI patients. Using mean diffusivity of the right cingulum-angular bundle, DAI and MTBI could be discriminated with an area under the curve of 94%. Both DAI and MTBI exhibited scattered axonal degeneration; however, DAI appeared to exhibit more pronounced axonal degeneration in the ampulla of the corpus callosum than MTBI. Our results suggest that DAI and MTBI can be accurately distinguished using DTI.

Efficacy and Safety of OnabotulinumtoxinA 400 Units in Patients with Post-Stroke Upper Limb Spasticity: Final Report of a Randomized, Double-Blind, Placebo-Controlled Trial with an Open-Label Extension Phase.

In many countries, 400 units (U) is the maximum dose of onabotulinumtoxinA available to treat upper limb spasticity, but few studies have demonstrated the optimal use of this dose. In the double-blind phase of this randomized, controlled trial, we compared the efficacy and safety of 400 vs. 240 U onabotulinumtoxinA in patients with post-stroke upper limb spasticity. Both groups received 240 U onabotulinumtoxinA injected in the forearm. An additional 160 U onabotulinumtoxinA (400 U group) or placebo (240 U group) was injected in the elbow flexors. Both groups showed similar muscle tone reduction in the wrist, fingers, and thumb; muscle tone reduction in the elbow flexors was greater in the group treated with onabotulinumtoxinA (400 U group) compared to placebo (240 U group). Functional disabilities improved in both groups. No substantial difference was found in safety profiles. In the subsequent open-label phase, all participants received repeat injections of 400 U onabotulinumtoxinA (target muscles and doses per muscle determined by the physician). Similar efficacy and safety outcomes, as with the 400 U group in the double-blind phase, were confirmed. This final report demonstrates that injection of onabotulinumtoxinA 400 U relieves muscle tone in a wide range of areas and improves functional disabilities; generally, it was well-tolerated, and no new safety concerns were identified. The dosing data in the open-label phase will inform optimal use of onabotulinumtoxinA in clinical practice (ClinicalTrials.gov: NCT03261167).

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.

[Memory Rehabilitation for Amnesic with Acquired Brain Injury].

Two theoretical frameworks based on cognitive rehabilitation principles are recommended for the rehabilitation of memory impaired individuals. The first is improving memory function by the remediation of brain plasticity, known as remediation-oriented rehabilitation, and second is the compensation of memory function through the use of external memory aids, environmental modifications, and intact cognitive functions to overcome limitations in daily life. In rehabilitation of episodic memory impaired individuals, it has been recognized that the effortful active retrieval technique is more effective than the memorization technique. In contrast, the errorless learning technique with high-effort conditions and the active participation of patients has been recognized to be particularly effective in directly improving impaired episodic memory systems. More recently, another mnemonic strategy called the spaced retrieval technique has gained support. The theoretical components of spaced retrieval consist of classical conditioning, priming, the spacing effect, and errorless learning by taking advantage of the implicit memory system, which is preserved in many people with memory loss.

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.

A new type of gene-disruption cassette with a rescue gene for Pichia pastoris.

Pichia pastoris has been used for the production of many recombinant proteins, and many useful mutant strains have been created. However, the efficiency of mutant isolation by gene-targeting is usually low and the procedure is difficult for those inexperienced in yeast genetics. In order to overcome these issues, we developed a new gene-disruption system with a rescue gene using an inducible Cre/mutant-loxP system. With only short homology regions, the gene-disruption cassette of the system replaces its target-gene locus containing a mutation with a compensatory rescue gene. As the cassette contains the AOX1 promoter-driven Cre gene, when targeted strains are grown on media containing methanol, the DNA fragment, i.e., the marker, rescue and Cre genes, between the mutant-loxP sequences in the cassette is excised, leaving only the remaining mutant-loxP sequence in the genome, and consequently a target gene-disrupted mutant can be isolated. The system was initially validated on ADE2 gene disruption, where the disruption can easily be detected by color-change of the colonies. Then, the system was applied for knocking-out URA3 and OCH1 genes, reported to be difficult to accomplish by conventional gene-targeting methods. All three gene-disruption cassettes with their rescue genes replaced their target genes, and the Cre/mutant-loxP system worked well to successfully isolate their knock-out mutants. This study identified a new gene-disruption system that could be used to effectively and strategically knock out genes of interest, especially whose deletion is detrimental to growth, without using special strains, e.g., deficient in nonhomologous end-joining, in P. pastoris. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1201-1208, 2017.

Effects of botulinum toxin A therapy and multidisciplinary rehabilitation on upper and lower limb spasticity in post-stroke patients.

OBJECTIVES: The purpose of this study was to examine the effects of combined botulinum toxin type A (BoNT-A) and inpatient multidisciplinary (MD) rehabilitation therapy on the improvement of upper and lower limb function in post-stroke patients. METHODS: In this retrospective study, a 12-day inpatient treatment protocol was implemented on 51 post-stroke patients with spasticity. Assessments were performed on the day of admission, at discharge, and at 3 months following discharge. RESULTS: At the time of discharge, all of the evaluated items showed a statistically significant improvement. Only the Functional Reach Test (FRT) showed a statistically significant improvement at 3 months. In subgroup analyses, the slowest walking speed group showed a significantly greater change ratio of the 10 Meter Walk Test relative to the other groups, from the time of admission to discharge. This group showed a greater FRT change ratio than the other groups from the time of admission to the 3-month follow-up. CONCLUSION: Inpatient combined therapy of simultaneous injections of BoNT-A to the upper and lower limbs and MD may improve motor function.

Does sensory transcutaneous electrical stimulation prevent pneumonia in the acute stage of stroke? A preliminary study.

Acute stroke patients with dysphagia are at risk of developing pulmonary infection, which increases the risk of death. Therefore, optimal management of dysphagia is essential; however, available evidence supporting the effectiveness of dysphagia treatments is limited. Surface electrical stimulation (e-stim) has been developed as a new treatment modality for dysphagia. In this study, we investigated the efficacy of surface sensory e-stim therapy in preventing pulmonary infection in 53 acute stroke patients with dysphagia. The risk of pulmonary infection was significantly decreased in the general dysphagia/surface e-stim combination therapy group. We considered that surface e-stim therapy can impact dysphagia treatment in acute stroke patients, particularly in preventing pulmonary infection. Future large and randomized studies are needed to evaluate the effects of surface sensory e-stim therapy on acute stroke patients.

Combination Protocol of Low-Frequency rTMS and Intensive Occupational Therapy for Post-stroke Upper Limb Hemiparesis: a 6-year Experience of More Than 1700 Japanese Patients.

Several years ago, we proposed a combination protocol of repetitive transcranial magnetic stimulation (rTMS) and intensive occupational therapy (OT) for upper limb hemiparesis after stroke. Subsequently, the number of patients treated with the protocol has increased in Japan. We aimed to present the latest data on our proposed combination protocol for post-stroke upper limb hemiparesis as a result of a multi-institutional study. After confirming that a patient met the inclusion criteria for the protocol, they were scheduled to receive the 15-day inpatient protocol. In the protocol, two sessions of 20-min rTMS and 120-min occupational therapy were provided daily, except for Sundays and the days of admission/discharge. Motor function of the affected upper limb was evaluated by the Fugl-Meyer assessment (FMA) and Wolf motor function test (WMFT) at admission/discharge and at 4 weeks after discharge if possible. A total of 1725 post-stroke patients were studied (mean age at admission 61.4 ± 13.0 years). The scheduled 15-day protocol was completed by all patients. At discharge, the increase in FMA score, shortening in performance time of WMFT, and increase in functional ability scale (FAS) score of WMFT were significant (FMA score 46.8 ± 12.2 to 50.9 ± 11.4 points, p < 0.001; performance time of WMFT 2.57 ± 1.32 to 2.21 ± 1.33, p < 0.001; FAS score of WMFT 47.4 ± 14. to 51.4 ± 14.3 points, p < 0.001). Our proposed combination protocol can be a potentially safe and useful therapeutic intervention for upper limb hemiparesis after stroke, although its efficacy should be confirmed in a randomized controlled study.

[Fundamental theory and practice in stroke rehabilitation from acute stage to chronic stage].

One of the most important objects of stroke rehabilitation is motor recovery from acute stage to chronic stage. Reorganization theory of motor circuits in the cerebral cortex contributing to recovery following stroke is proposed. In acute stage motor recovery depends on residual corticospinal tract excitability from onset to 3 months (1(st) stage recovery) . In next stage alternative output system is used according to intracortical excitability depending on intracortical disinhibition at the peak of 3 months (2(nd) stage recovery) . At 6 months and beyond training-induced synaptic strengthening becomes better established, and new networks are better reorganized (3(rd)stage recovery) . Stroke rehabilitation programs from acute stage are required depending on this stage theory. With each stage to select and perform the most effective rehabilitation programs are necessary. Two obstruction factors of motor recovery are indicated. One of them is Wallerian degeneration of corticospinal tract. Early Wallerian degeneration of the corticospinal tract that is seen on diffusion weighted MRI was reported. The appearance of Wallerian degeneration at acute stage should be directed to more attention as motor recovery inhibition. Next obstruction factor is development of spasticity from acute stage. Spastic paresis is subjected over time to immobilization of the paretic body part and chronic disuse of the paretic body part, which are avoidable through early rehabilitation intervention. Recently various interventions were proposed for motor recovery. The combination of repetitive transcranial magnetic stimulation and intensive occupational therapy by Abo (2010) are recommended to recovery hand function at chronic stage as 3(rd) stage recovery.

Effect of nisin (Nisaplin) on the growth of Listeria monocytogenes in Karashi-mentaiko (Red-pepper Seasoned Cod Roe).

The influence of Nisaplin, which contains 2.5% nisin, on the growth of Listeria monocytogenes in Karashi-mentaiko (red-pepper seasoned cod roe) was investigated. The MICs of Nisaplin for L. monocytogenes (10(8) CFU/mL) were measured; seven isolates showed a value of 1,600 microg/mL and one isolate showed a value of 800 microg/mL. All L. monocytogenes isolates had a MIC of 800 microg/mL at 10(6) CFU/mL. The number of L. monocytogenes in Karashi-mentaiko stored at 4 degrees C was decreased by Nisaplin added at 60 and 600 microg/g. These results indicated that Nisaplin effectively inhibits the growth of L. monocytogenes in Karashi-mentaiko.