Combined effects of botulinum toxin type A and repetitive transcranial magnetic stimulation with intensive motor training immediately after injection in a patient with chronic stroke: A case report.

STUDY DESIGN: Single case report. INTRODUCTION: A previous study clarified that spasticity and motor function were improved by combined treatment with botulinum toxin type A (BTX) injection and 1-Hz repetitive transcranial magnetic stimulation (rTMS) with intensive motor training at 4 weeks after injection. However, it is not clear whether 1-Hz rTMS with intensive motor training immediately after BTX injection also improves spasticity and motor function in stroke patients. PURPOSE OF THE CASE REPORT: The purpose of this case report is to test the short- and long-term effects of BTX injection and rTMS with intensive motor training on the spasticity, motor function, and usefulness of the paretic hand in a stroke patient. METHODS: A 64-year-old male, who suffered from a right cerebral hemorrhage 53 months previously, participated in the present study. BTX was injected into the spastic muscles of the affected upper limb. He then received the new protocol for a total of 24 sessions. The Modified Ashworth Scale (MAS), Fugl-Meyer Assessment (FMA), and Motor Activity Log, consisting of the amount of use and quality of movement scales, were assessed before and immediately after BTX injection, at discharge, and monthly for up to 5 months after discharge. RESULTS: For the short-term effects of the therapy, the MAS scores of the elbow and wrist, FMA score, and quality of movement score improved. For the long-term effects of the therapy, the MAS score of the fingers, FMA score, and amount of use score improved for up to 5 months after discharge. CONCLUSIONS: The present case report showed the improvement of all assessments performed in the short and/or long term and suggest the possibility of shortening the intervention period of combined therapy of BTX and rTMS with intensive motor training.

Hindlimb-unloading suppresses B cell population in the bone marrow and peripheral circulation associated with OPN expression in circulating blood cells.

Rodent hindlimb unloading (HU) by tail-suspension is a model to investigate disuse-induced bone loss in vivo. Previously, we have shown that osteopontin (OPN, also known as Spp1) is required for unloading-induced bone loss. However, how unloading affects OPN expression in the body is not fully understood. Here, we examined OPN expression in peripheral blood of mice subjected to HU. Real-time RT-PCR analysis indicated that OPN expression is increased in circulating peripheral blood cells. This HU-induced increase in OPN mRNA expression was specific in circulating peripheral blood cells, as OPN was not increased in the blood cells in bone marrow. HU-induced enhancement in OPN expression in peripheral blood cells was associated with an increase in the fraction of monocyte/macrophage lineage cells in the peripheral blood. In contrast, HU decreased the fraction size of B-lymphocytes in the peripheral blood. We further examined if B-lymphogenesis is affected in the mice deficient for osteopontin subjected to HU. In bone marrow, HU decreased the population of the B-lymphocyte lineage cells significantly, whereas it did not alter the population of monocyte/macrophage lineage cells. HU also increased the cells in T-lymphocyte lineage in bone marrow. Interestingly, these changes were observed similarly both in OPN-deficient and wild-type mice. These results indicate for the first time that HU increases OPN expression in circulating cells and suppresses bone marrow B-lymphogenesis.

Effect of intensive motor training with repetitive transcranial magnetic stimulation on upper limb motor function in chronic post-stroke patients with severe upper limb motor impairment.

Background Intensive motor training with low-frequency repetitive transcranial magnetic stimulation (rTMS) has efficacy as a therapeutic method for motor dysfunction of the affected upper limb in patients with mild to moderate stroke. However, it is not clear whether this combination therapy has the same effect in chronic post-stroke patients with severe upper limb motor impairment. Objectives The aim of this study was to test the treatment effects of intensive motor training with low-frequency rTMS in chronic post-stroke patients with severe upper limb motor impairment. Methods A convenience sample of 26 chronic post-stroke patients with severe upper limb motor impairment participated in this study with the non-randomized, non-controlled clinical trial. All subjects were hospitalized to receive intensive motor training with low-frequency rTMS. During 2 weeks in which Sundays were excluded, a total of 24 sessions (2 sessions per day) of the intervention were conducted. The Fugl-Meyer Assessment (FMA) and Wolf Motor Function Test (WMFT) were used to assess motor impairment and function of the affected upper limb, respectively, before and after intervention. Paired t-test was used to analyze the effects of the intervention. Results The FMA total score and WMFT log performance time significantly improved from before to after intervention (FMA: 12.6-18.0; WMFT: 3.6-3.3, p < 0.001). Conclusions The present results suggest that intensive motor training with low-frequency rTMS could improve motor impairment in chronic post-stroke patients with severe upper limb motor impairment and contribute to the expansion of the application range of this combination therapy.

NMES with rTMS for moderate to severe dysfunction after stroke.

BACKGROUND: Motor dysfunction after stroke might be improved by neuromuscular electrical stimulation (NMES) combined with 1 Hz repetitive transcranial magnetic stimulation (rTMS) in patients with moderate and severe motor dysfunction. OBJECTIVE: This preliminary study tested the effect of this treatment combination. METHODS: Fifteen patients (60.5 ± 10.3 years old) participated in the study. All patients had been affected by cerebral artery infarction or hemorrhage and had moderate or severe motor dysfunction in their affected hand. The patients received NMES at paretic wrist extensor muscles combined with rTMS over the unaffected M1 hemisphere twice a day, six days/week over two weeks. All participants underwent the following battery of tests to evaluate the motor function of the affected hand: Upper limb Fugl-Meyer Assessment (UFMA), Wolf Motor Function Test (WMFT), and Box and Block Test (BBT). RESULTS: UFMA, WMFT, and BBT scores improved significantly after the study. CONCLUSIONS: These results suggest that NMES combined with rTMS could be useful for recovery of moderate and severe motor function after stroke.

The effects of high-frequency transcranial magnetic stimulation combined with transcutaneous electrical stimulation in a severe stroke patient.

The case report describes the effects of 5 Hz repetitive transcranial magnetic stimulation (rTMS) combined with transcutaneous electrical stimulation (TES) in a patient with severe stroke. The patient was a 69-year-old male who was affected by a left middle cerebral artery infarction. The patient had no movement in his right hand. To assess the effects, cerebral blood flow and motor function were measured before and after treatment. This treatment delivered rTMS over the affected M1 with TES at the paretic wrist extensor muscles for 10 days. The regional cerebral blood flow (rCBF) in the entire brain was measured by positronemission tomography. To evaluate the motor function, the Fugl-Meyer assessment (FMA) was used. After treatment, the rCBF was increased (except for the stimulated region), and the FMA score was slightly improved. These results suggest the potential therapeutic use of rTMS combined with TES for recovery in severe stroke.

Growth factors and proliferation of cultured rat gingival cells in response to cyclosporin A.

OBJECTIVE: The prominent side-effect of cyclosporin A, an immunosuppressive drug, in oral tissues is gingival outgrowth, although the exact mechanism underlying this side-effect is unclear. The main purposes of the present study were to determine whether cyclosporin A induced the gingival outgrowth by promoting proliferation of gingival cells and whether growth factors such as transforming growth factor-betas (TGF-betas), fibroblast growth factor-2 (FGF-2), platelet-derived growth factors (PDGFs), and insulin-like growth factors (IGFs) are involved in the possible changes in the proliferation of gingival cells induced by cyclosporin A. METHODS: Cells isolated from rat gingival tissues were cultured with cyclosporin A or IGF-I for 3 days. The effects of cyclosporin A or IGF-I on the proliferation of cultured rat gingival cells were analyzed with a CellTiter 96 proliferation assay kit. The mRNA expression levels for TGF-betas, FGF-2, PDGFs, IGFs, insulin-like growth factor receptors (IGFRs), and insulin-like growth factor binding proteins (IGFBPs) in the rat gingival cells treated with cyclosporin A were measured using competitive reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Cyclosporin A induced 23-25% (p < 0.001) increases in the proliferation of rat gingival cells and approximately 130% (p < 0.05) and 60% (p < 0.05) elevations in the mRNA expression levels for TGF-beta1 and FGF-2, respectively. On the other hand, exogenous IGF-I induced 8-11% (p < 0.05) increases in the proliferation, but cyclosporin A induced 30-80% (p < 0.05-0.01) reductions in the mRNA expression levels for endogenous IGF-I, IGFR1, IGFBP2, IGFBP3, IGFBP5, and IGFBP6. CONCLUSIONS: Cyclosporin A stimulates the proliferation of rat gingival cells. TGF-beta1 and FGF-2 could be involved, but IGFs, IGFRs and IGFBPs could not be directly involved in this cyclosporin A induced-stimulation of the gingival cell proliferation.

Exogenous hepatocyte growth factor inhibits myoblast differentiation by inducing myf5 expression and suppressing myoD expression in an organ culture system of embryonic mouse tongue.

We examined the effects of exogenous hepatocyte growth factor (HGF) on the differentiation and proliferation of tongue myoblasts by using an organ culture system of tongue obtained from mouse embryos at embryonic day (E) 13. Exogenous HGF induced reductions in the quantities of muscle creatine kinase and myogenin mRNAs and in the number of fast myosin heavy chain-positive myoblasts and myotubes, suggesting that HGF suppressed the differentiation of myoblasts in the cultured E13 tongues. Exogenous HGF induced no significant changes in the percentage of proliferating cell nuclear antigen (PCNA)-positive cell nuclei to total cell nuclei (labeling index) in the muscle portion of the cultured E13 tongue, suggesting that HGF did not affect the proliferation of myoblasts. Exogenous HGF induced the expression of myf5 mRNA but inhibited the expression of myoD mRNA. Since mouse tongue myoblasts are reported to complete proliferation by E13, it appears that exogenous HGF arrests myoblasts in the cell cycle and does not allow them to enter the differentiation process. This is achieved by controlling the expression of myf5 and myoD mRNAs, thus inhibiting the differentiation of tongue myoblasts.