[Show abstract][Hide abstract] ABSTRACT: We clarified the safety, feasibility, and efficacy of atomoxetine administration combined with intensive speech therapy (ST) for patients with post-stroke aphasia. In addition, we investigated the effect of atomoxetine treatment on neural activity of surrounding lesioned brain areas.
Four adult patients with motor-dominant aphasia and a history of left hemispheric stroke were studied. We have registered on the clinical trials database (ID: JMA-IIA00215). Daily atomoxetine administration of 40 mg was initiated 2 weeks before admission and raised to 80 mg 1 week before admission. During the subsequent 13-day hospitalization, administration of atomoxetine was raised to 120 mg and daily intensive ST (120 min/day, one-on-one training) was provided. Language function was assessed using the Japanese version of The Western Aphasia Battery (WAB) and the Token test 2 weeks prior to admission, on the day of admission, and at discharge. At 2 weeks prior to admission and at discharge, each patient's cortical blood flow was measured using (123)I-IMP-single photon emission computed tomography (SPECT).
This protocol was successfully completed by all patients without any adverse effects. Four patients showed improved language function with the median of the Token Test increasing from 141 to 149, and the repetition score of WAB increasing from 88 to 99. In addition, cortical blood flow surrounding lesioned brain areas was found to increase following intervention in all patients.
Atomoxetine administration and intensive ST was safe and feasible for post-stroke aphasia, suggesting its potential usefulness in the treatment of this patient population.
The International journal of neuroscience 08/2015; DOI:10.3109/00207454.2015.1074226 · 1.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We provided an intervention to chronic post-stroke aphasic patients using low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) guided by a functional magnetic resonance imaging (fMRI) evaluation of language laterality, combined with intensive speech therapy (ST). We performed a single photon emission-computed tomography (SPECT) scan pre- and post-intervention and investigated the relationship between cerebral blood flow (CBF) and language function. Fifty right-handed chronic post-stroke aphasic patients were enrolled in the study. During their 11-day hospital admission, the patients received a 40-min session of 1-Hz LF-rTMS on the left or right hemisphere, according to language localization identified by the fMRI evaluation, and intensive ST daily for 10 days, except for Sunday. A SPECT scan and language evaluation by the Standard Language Test of Aphasia (SLTA) were performed at the time of admission and at 3 months following discharge. We calculated laterality indices (LIs) of regional CBF (rCBF) in 13 language-related Brodmann area (BA) regions of interest. In patients who received LF-rTMS to the intact right hemisphere (RH-LF-rTMS), the improvement in the total SLTA score was significantly correlated with the pre- and post-intervention change of LI (ΔLI) in BA44. In patients who received LF-rTMS to the lesional left hemisphere (LH-LF-rTMS), this association was not observed. Analyses of the SLTA subscales and rCBF ΔLI demonstrated that in the RH-LF-rTMS group, the SLTA Speaking subscale scores were significantly correlated with ΔLIs in BA11, 20, and 21, and the SLTA Writing subscale scores were significantly correlated with ΔLIs in BA6 and 39. Conversely, in the LH-LF-rTMS group, the SLTA Speaking subscale scores were correlated with ΔLI in BA10, and the SLTA Reading subscale scores were significantly correlated with ΔLIs in BA13, 20, 22, and 44. Our results suggest the possibility that fMRI-guided LF-rTMS combined with intensive ST may affect CBF and contribute to the improvement of language function of post-stroke aphasic patients. LF-rTMS to the non-lesional and lesional hemispheres showed a difference in the associations between language performance and CBF. The results indicate that more effective rTMS intervention needs to be explored for patients who show right hemisphere language activation in an fMRI language evaluation.
Translational Stroke Research 08/2015; 6(5). DOI:10.1007/s12975-015-0417-7 · 2.44 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Atomoxetine, a selective noradrenaline reuptake inhibitor, has been reported to enhance brain plasticity, but has not yet been used in stroke patients. We reported the feasibility and clinical benefits on motor functional recovery of the combination of repetitive transcranial magnetic stimulation (rTMS) and intensive occupational therapy (OT) in stroke patients. This pilot study was designed to evaluate the additive effects of oral atomoxetine to rTMS/OT in post-stroke hemiparetic patients. The study included three post-stroke patients with upper limb hemiparesis. Treatment with 40 mg/day atomoxetine commenced 2 weeks before admission. After confirming tolerance, the dose was increased to 120 mg/day. Low-frequency rTMS/OT was provided daily for 15 days during continued atomoxetine therapy. Motor function of the affected upper limb was evaluated with the Fugl-Meyer Assessment and Wolf Motor Function test. All patients completed the protocol and showed motor improvement up to 4 weeks after the treatment. No atomoxetine-related side effects were noted. Our protocol of triple therapy of atomoxetine, low-frequency rTMS, and OT is safe and feasible intervention for upper limb hemiparesis after stroke.
[Show abstract][Hide abstract] ABSTRACT: Objectives:
The purpose of the present study was to investigate potential effects of ankle-foot orthoses (AFOs) on the functional recovery of post-acute stroke patients following rehabilitation.
Subjects and methods:
This study is a retrospective cohort study. Participants were in-hospital stroke patients registered in the Japan Rehabilitation Database between 2005 and 2012. A total of 1862 patients were eligible after applying exclusion criteria. Propensity score analysis was applied to adjust for potential bias and to create two comparable groups. An additional subset analysis focused on Functional Independence Measure (FIM) scores on admission.
In this sample, 30.7% of 1863 eligible patients were prescribed AFOs. Propensity score matched analysis showed that patients with AFOs had significantly higher scores than those without them for discharge FIM (mean: 91.3 vs 85.8; p=0.02), FIM gain (mean: 28.9 vs 23.5; p<0.001), and FIM efficiency (mean: 0.27 vs 0.22; p<0.001). Inverse probability weighting analysis showed similar results. In the subset analysis, patients with AFOs had significantly higher discharge FIM compared with those without them in the low admission FIM subgroup only. In addition, patients with AFOs performed independent exercise more than those without them (p<0.001).
These data suggest that stroke survivors may have better functional recovery if they are prescribed an AFO than if they are not prescribed an AFO. The use of AFOs is considered to be a feasible option to improve functional recovery of stroke rehabilitation patients.
PLoS ONE 04/2015; 10(4):e0122688. DOI:10.1371/journal.pone.0122688 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
The purpose of this study was to determine whether local injection of botulinum toxin type A (BoNT-A) into the spastic muscles has any added benefits to repetitive transcranial magnetic stimulation (RTMS)/occupational therapy (OT) in patients with spastic upper limb hemiparesis.
The study subjects of 80 post-stroke patients with spastic upper limb hemiparesis (age: 60.2 ± 13.0 years, time after stroke: 55.3 ± 43.0 months), were divided into the BoNT-A plus RTMS/OT group and RTMS/OT group. BoNT-A was injected into the spastic muscles (total dose: 240 units) before RTMS/OT. The latter included 12 sessions of 40 min RTMS over the non-lesional hemisphere and 240-min intensive OT daily over 15 days. Spasticity was evaluated by the modified Ashworth scale (MAS) and the motor function of the affected upper limb was evaluated serially with Fugl-Meyer Assessment and Wolf Motor Function Tests.
Both groups showed significant improvements in spasticity and motor function. The addition of BoNT-A resulted in better improvement in FMA score and MAS of finger flexor muscles (p < 0.05).
The triple-element protocol of local injection of BoNT-A into spastic finger muscles, RTMS and intensive OT, is a promising therapeutic program for post-stroke spastic upper limb hemiparesis, although its significance should be confirmed in randomized, placebo-controlled trials.
European Neurology 10/2014; 72(5-6):290-298. DOI:10.1159/000365005 · 1.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The effects of testosterone on functional recovery in stroke patients have not previously been studied. The purpose of the study was to determine the effects of pre-rehabilitation serum testosterone levels on functional recovery in male stroke patients. In total, 111 male stroke patients admitted to our department were enrolled in the study (age: 74 ± 10 years, days from stroke onset: 36 ± 14 days). Serum concentration of free testosterone (Free-T) was measured upon admission. Patients were also evaluated using the Functional Independence Measure (FIM) at admission and discharge. The main outcome variable was FIM at discharge. Correlations between Free-T and FIM were evaluated using Spearman's rank-order correlation coefficients. We performed multivariate linear regression analysis to assess the effects of testosterone on functional outcome with adjustment for patient background variables. In addition, we added a subgroup analysis based on age. The average Free-T serum concentration was 4.7 ± 1.7 pg/ml. There was a significant positive correlation between Free-T and discharge FIM. The multivariate linear regression model showed that Free-T concentration was significantly associated with FIM at discharge (β = 0.09; P = 0.01). In the subgroup analysis, Free-T had significant association with discharge FIM only in patients under 76 years old (β = 0.24; P < 0.001). Our data suggest that serum Free-T levels have a positive effect for discharge FIM in male stroke patients.
[Show abstract][Hide abstract] ABSTRACT: Background:
High- and low-frequency repetitive transcranial magnetic stimulation (HF-rTMS and LF-rTMS) has been shown to be beneficial for upper limb hemiparesis in patients with acute stroke. However, no study has examined the usefulness of bilateral application of HF- and LF-rTMS (BL-rTMS).
Fifty-eight hemiparetic patients with acute stroke were randomly assigned into two groups: HF-rTMS group and BL-rTMS group. All patients were scheduled to receive five sessions of either HF-rTMS over the lesional hemisphere or BL-rTMS over both hemispheres for 5 days. Motor function of the affected upper limb was evaluated using the Brunnstrom Recovery Stage (BRS) for upper-limb and hand-fingers, grip strength and tapping frequency, before the first session and after the last session of rTMS.
Improvement of BRS for the upper limb and hand/finger was significantly greater in the BL-rTMS group than the HF-rTMS group (p < 0.01). Improvement in grip strength and tapping frequency was also greater in the BL-rTMS group, although the differences were not statistically significant.
The proposed BL-rTMS is safe and feasible and showed a greater improvement of BRS of the affected upper limb compared to HF-rTMS. This novel rTMS approach may be a useful intervention for hemiparetic patients with acute stroke.
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to assess the safety, feasibility and efficacy of continuous theta-burst stimulation (cTBS) combined with intensive occupational therapy (OT) for upper limb hemiparesis after stroke. Ten patients with history of stroke and upper limb hemiparesis (age 62.0 ± 11.1 years, time since stroke 95.7 ± 70.2 months, mean ± SD) were studied. Each patient received 13 sessions, each comprising 160 s of cTBS applied to the skull on the area of the non-lesional hemisphere (using a 70-mm figure-8 coil, three pulse bursts at 50 Hz, repeated every 200 ms, i.e., 5 Hz, with total stimulation of 2,400 pulses), followed by intensive OT (comprising 120-min one-to-one training and 120-min self-training) during 15-day hospitalization. The motor function of the affected upper limb was evaluated by Fugl-Meyer Assessment (FMA) and Wolf Motor Function Test (WMFT) on the days of admission and discharge. All patients completed the 15-day protocol without any adverse effects. Treatment significantly increased the FMA score (from 46.6 ± 8.7 to 51.6 ± 8.2 points, p < 0.01) and shortened the log performance time of WMFT (from 2.5 ± 1.1 to 2.2 ± 1.2 s, p < 0.01). The 15-day protocol of cTBS combined with intensive OT is a safe and potentially useful therapeutic modality for upper limb hemiparesis after stroke.
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to clarify the safety and feasibility of a 6-day protocol of bilateral repetitive transcranial magnetic stimulation (rTMS) combined with intensive swallowing rehabilitation for chronic poststroke dysphagia. In-hospital treatment was provided to 4 poststroke patients (age at treatment: 56-80 years; interval between onset of stroke and treatment: 24-37 months) with dysphagia. Over 6 consecutive days, each patient received 10 sessions of rTMS at 3 Hz applied to the pharyngeal motor cortex bilaterally, followed by 20 min of intensive swallowing rehabilitation exercise. The swallowing function was evaluated by the Penetration Aspiration Scale (PAS), Modified Mann Assessment of Swallowing Ability (MMASA), Functional Oral Intake Scale (FOIS), laryngeal elevation delay time (LEDT) and Repetitive Saliva-Swallowing Test (RSST) on admission and at discharge. All patients completed the 6-day treatment protocol and none showed any adverse reactions throughout the treatment. The combination treatment improved laryngeal elevation delay time in all patients. Our proposed protocol of rTMS plus swallowing rehabilitation exercise seems to be safe and feasible for chronic stroke dysphagia, although its efficacy needs to be confirmed in a large number of patients.
Case Reports in Neurology 03/2014; 6(1):60-7. DOI:10.1159/000360936
[Show abstract][Hide abstract] ABSTRACT: Background:
The combination protocol of repetitive transcranial magnetic stimulation (RTMS) and intensive occupational therapy (OT) improves motor function of the paretic upper limb in poststroke patients. However, the effect of RTMS/OT on motor neuron excitability remains to be investigated. The purpose of this study was to determine the effect of 15-day application of RTMS/OT on motor neuron excitability in such patients using neurophysiological studies including F-wave parameter measurements.
Subjects and methods:
Ten poststroke patients with spastic upper limb hemiparesis were studied (mean age: 57.4 ± 8.1 years, ± SD). Patients were hospitalized for 15 days to receive RTMS/OT. One session of 40-min low-frequency RTMS and two sessions of 120-min intensive OT were provided daily. Neurophysiological studies including F-wave parameters measurements were performed on the days of admission/discharge. Motor function and spasticity of the affected upper limb were evaluated on the same time points.
RTMS/OT significantly improved motor function of the affected upper limb. RTMS/OT decreased the modified Ashworth scale (MAS) in the affected upper limb (p < 0.05), but did not change F-wave frequency in either upper limb. However, both F-mean/M ratio and F-max/M ratio significantly decreased in the affected upper limb (all p < 0.05).
The 15-day protocol of LF-RTMS/OT produced significant reduction of motor neuron excitability. RTMS/OT can potentially produce significant reduction in upper limb spasticity in the affected upper limb, although this finding should be confirmed in a larger number of patients.
The International journal of neuroscience 02/2014; 125(1). DOI:10.3109/00207454.2014.897706 · 1.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recently, the usefulness of neuromuscular electrical stimulation and repetitive transcranial magnetic stimulation for poststroke dysphagia has been reported. However, there is no report that describes the effectiveness of functional magnetic stimulation (FMS) for dysphagia. The purpose of this study is to clarify the effectiveness of FMS for poststroke dysphagia.
Twenty poststroke dysphagic patients (age at treatment: 51-80 years; interval between onset of stroke and treatment: 6 to 36 months) were randomly assigned to a real group or a sham group. In the real group, FMS of 30 Hz was applied for suprahyoid muscles in a 20-sec train using a parabolic coil for 10 min (total 1200 pulses). In the sham group, sham stimulation was applied for 10 min at the same site. Swallowing function was evaluated by the timed water swallow test, interswallow interval (ISI), swallowing volume velocity (speed), and volume per swallow (capacity) were measured before and after stimulation.
All patients completed the stimulation and none showed any adverse reactions throughout the stimulation. The improvement of speed and capacity of swallowing after stimulation was significantly larger in the real group compared with the sham group (all p < 0.05). However, no significant difference in the ISI was found between the groups.
FMS using a parabolic coil can potentially improve swallowing function in poststroke dysphagic patients.