BackgroundRepetitive 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.ObjectivesTo 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.MethodsPoststroke 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.ResultsTwo-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.ConclusionsThe 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.

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.

Although repetitive transcranial magnetic stimulation (rTMS) for upper limb motor area in stroke patients is beneficial, it has been poorly investigated in rTMS for leg motor area. Furthermore, no study has examined the usefulness of rTMS for leg motor area in patients in the early phase of stroke. Twenty-one patients with a hemispheric stroke lesion in the early phase were randomly assigned into two groups: the high-frequency (HF)-rTMS group [N = 11] and the sham stimulation group [N = 10]. Patients received rTMS for 5 consecutive days, beginning 10.9 ± 6.6 days on average after the onset. Brunnstrom Recovery Stages (BRS) for the lower limbs and the Ability for Basic Movement Scale Revised (ABMS II) were assessed before and after the intervention. The improvement in BRS for the lower limbs was significant after the intervention in the HF-rTMS group. Although both the HF-rTMS and sham stimulation groups had significant improvements in ABMS II scores, the extent of improvement in the AMBS II was significantly greater in the HF-rTMS group than in the sham stimulation group. Application of HF-rTMS over the bilateral leg motor areas has potential to be a new rehabilitation therapy for patients in the acute phase of stroke.

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.

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 Tc-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.