Masachika Niimi

Role of Brain-Derived Neurotrophic Factor in Beneficial Effects of Repetitive Transcranial Magnetic Stimulation for Upper Limb Hemiparesis after Stroke.

Background Repetitive transcranial magnetic stimulation (rTMS) can improve upper limb hemiparesis after stroke but the mechanism underlying its efficacy remains elusive. rTMS seems to alter brain-derived neurotrophic factor (BDNF) and such effect is influenced by BDNF gene polymorphism. Objectives To investigate the molecular effects of rTMS on serum levels of BDNF, its precursor proBDNF and matrix metalloproteinase-9 (MMP-9) in poststroke patients with upper limb hemiparesis. Methods Poststroke patients with upper limb hemiparesis were studied. Sixty-two patients underwent rehabilitation plus rTMS combination therapy and 33 patients underwent rehabilitation monotherapy without rTMS for 14 days at our hospital. One Hz rTMS was applied over the motor representation of the first dorsal interosseous muscle on the non-lesional hemisphere. Fugl-Meyer Assessment and Wolf Motor Function (WMFT) were used to evaluate motor function on the affected upper limb before and after intervention. Blood samples were collected for analysis of BDNF polymorphism and measurement of BDNF, proBDNF and MMP-9 levels. Results Two-week combination therapy increased BDNF and MMP-9 serum levels, but not serum proBDNF. Serum BDNF and MMP-9 levels did not correlate with motor function improvement, though baseline serum proBDNF levels correlated negatively and significantly with improvement in WMFT (ρ = -0.422, p = 0.002). The outcome of rTMS therapy was not altered by BDNF gene polymorphism. Conclusions The combination therapy of rehabilitation plus low-frequency rTMS seems to improve motor function in the affected limb, by activating BDNF processing. BDNF and its precursor proBDNF could be potentially suitable biomarkers for poststroke motor recovery.

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.

The Efficacy of High-Frequency Repetitive Transcranial Magnetic Stimulation for Improving Apathy in Chronic Stroke Patients

Although repetitive transcranial magnetic stimulation (rTMS) for hemiparesis is beneficial, so far no study has examined the usefulness of rTMS for apathy. Thirteen patients with chronic stroke were assigned randomly to 2 groups: rTMS group (n = 7) and sham stimulation group (n = 6). The patients received 5 sessions of either high-frequency rTMS over the region spanning from the dorsal anterior cingulate cortex (dACC) to medial prefrontal cortex (mPFC) or sham stimulation for 5 days. The severity of apathy was evaluated using the Apathy Scale (AS) and the severity of depression was evaluated using the Quick Inventory of Depressive Symptomatology (QIDS) serially before and after the 5-day protocol. The AS and QIDS scores were significantly improved in the rTMS group, although they were not changed in the sham stimulation group. The degree of change in the AS score was significantly greater in the rTMS group than that in the sham stimulation group. The degree of change in the QIDS score was greater in the rTMS group than that in the sham stimulation group, although the difference was not statistically significant. The application of high frequency rTMS over the dACC and mPFC may be a useful intervention for apathy due to stroke.

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

ABSTRACT 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.

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.

Improvement of higher brain dysfunction after brain injury by repetitive transcranial magnetic stimulation and intensive rehabilitation therapy: case report

Repetitive transcranial magnetic stimulation (rTMS) and intensive cognitive rehabilitation (CR) were administered to two patients with cognitive dysfunction following brain injury. The first case was a 67-year-old man who presented with memory dysfunction, attention dysfunction, and decreased insight following diffuse axonal injury. High-frequency rTMS (10 Hz, 2400 pulses/day) targeting the anterior cingulate using a navigation system and CR were administered for 12 days at 1 year from the onset of injury. The patient showed improved neuropsychological performance and activities of daily living. In addition, single photon emission computer tomography with 99mTc-ECD showed improved perfusion in the anterior cingulate gyrus. The second case was a 68-year-old man who presented with dysfunction of memory, attention, and executive function following a cerebral infarction in the middle cerebral artery region within the right hemisphere. This patient received 12 days (except for Sundays) of low-frequency rTMS (1 Hz, 1200 pulses/day) targeting the left dorsolateral prefrontal cortex and the left posterior parietal cortex and CR. Following this intervention, the patient’s neuropsychological performance and activities of daily living improved. Furthermore, single photon emission computer tomography showed changes in perfusion in the rTMS target sites and areas surrounding the targets. We have shown the safety and efficacy of rTMS therapy using a navigation system combined with intensive CR on two patients with cognitive dysfunction following brain injury. In addition, we observed changes in the areas around the rTMS target sites in brain imaging data.

Comparison of Functional Outcome between Lacunar Infarction and Branch Atheromatous Disease in Lenticulostriate Artery Territory.

BACKGROUND Branch atheromatous disease (BAD) is differentiated from lacunar infarction (LI). BAD is often associated with neurological deterioration in the acute stage, but outcome of BAD patients in the chronic stage is unclear. We aimed to explore the outcome of BAD in the lenticulostriate artery (LSA) territory in comparison with those of LI from the viewpoint of activities of daily living (ADLs). METHODS We retrospectively investigated patients who were admitted within 3 days after stroke onset. The patients underwent daily rehabilitation during hospitalization. BAD in LSA territory was defined by the presence of lesion representing 3 or more consecutive horizontal slices in magnetic resonance imaging. Patients having atrial fibrillation or more than 50% stenosis of the large artery in magnetic resonance angiography were excluded. We retrieved data on clinical characteristics and evaluation from medical records. RESULTS Subjects were 41 BAD and 35 LI patients. There was little difference in baseline characteristics. The National Institutes of Health Stroke Scale score was significantly higher in BAD patients (P < .05). The Barthel Index (BI) score and the Brunnstrom recovery stage were lower in BAD patients at admission (P < .05 and P < .05). Hospital stay was longer in BAD patients (P < .01), but the BI score at discharge was not different. To ambulate, 8 BAD and 1 LI patients depended on orthoses (P < .05), and 21 BAD and 7 LI patients used canes (P < .01). Multivariable analysis demonstrated that BAD lesion was correlated with AFO use independent of age and sex. CONCLUSIONS BAD patients can obtain ADLs similar to LI patients. However, many BAD patients require canes and/or orthoses.