Chronic Ischemic Stroke Patients Research Articles

The Psychophysiological Responses of the Chronic Ischemic Stroke Patients to the Acute Stress were Changed

Abstract: Mood disorder is one of the complications of stroke. The inability to cope with stress is also a prognosis of depression and anxiety. The aim of this study is to assess the response of stress system in the post stroke patients. Twelve healthy controls (HC) and twelve post-stroke patients after filling in the State-Trait Anxiety Inventory completed the Trier Social Stress Test (TSST) which induces acute stress. Salivary samples were collected to determine salivary cortisol levels and ECG record were taken in four times (before, right after stress, after two recoveries: 20 and 40 minutes after stress). ECG was also recorded during TSST and then the linear and non-linear features of Heart Rate Variability (HRV) were analyzed. The results showed that trait anxiety score and baseline salivary cortisol level were higher in post stroke than HC group (P-value <0.05). The increase of cortisol level after stress was only observed in HC that returned to baseline after the second recovery time. The stress increased the relative low frequency of HRV in both groups, however it was significantly lower in the stroke than HC group (P-value < 0.005). There was also a significant difference between alpha 1 DFA measures in stroke group and HC group (P-value <0.05). It is concluded that the impairment of the hormonal axis of stress system in the post-stroke patients that until now was not reported.

Anodal transcranial direct current stimulation enhances positive changes in movement functions, visual attention and depression of patients with chronic ischemic stroke: A clinical trial

Introduction: Stroke is one of the most serious and debilitating diseases in our society. Stroke survivors can suffer several neurological impairments. They typically show pathological changes in neural functions of brain areas. Transcranial direct current stimulation (tDCS) can be applied to modify cerebral excitability and has been recently applied in the treatment of neuropsychological and neurological disorders. The aim of the study herein was to evaluate changes in movement and cognitive functions of chronic ischemic stroke patients using anodic and cathodic tDCS.&#x0D; Method: In this clinical trial, 100 patients with chronic ischemic stroke were divided in 4 groups (control, sham, anodic tDCS, and cathodic tDCS; n=25 per group). The patients underwent routine treatment and received the same tDCS protocol (3 times per week of 30-min sessions during one month). Movement and cognitive functions were evaluated using the NIHSS Scale &amp; Trail Making Test and the Beck Test, before and after 1 and 3 months of tDCS sessions. All data were analyzed by 2-way repeated measures ANOVA using SPSS program (version 18).&#x0D; Results: The results showed that there were significant increases (P&lt;0.001) in NIHSS score and Barthel index between anodic group versus control, sham, or cathodic group, at various timepoints (before vs. 1 month after tDCS, 1 month vs. 3 months after tDCS, and before vs. 3 months after tDCS). Furthermore, there were significant decreases (P&lt;0.001) between anodic group versus control, sham, or cathodic group, at the various timepoints (before vs. 1 month after tDCS, 1 month vs. 3 months after tDCS, and before vs. 3 months after tDCS).&#x0D; Conclusion: Anodic tDCS has advantageous effects on movement and cognitive rehabilitation in stroke patients, but future studies are needed to further discern the differences and develop precise treatment protocols.&#x0D;

Two-year safety and clinical outcomes in chronic ischemic stroke patients after implantation of modified bone marrow-derived mesenchymal stem cells (SB623): a phase 1/2a study.

The aim of this study was to evaluate the safety and clinical outcomes associated with stereotactic surgical implantation of modified bone marrow-derived mesenchymal stem cells (SB623) in patients with stable chronic ischemic stroke. This was a 2-year, open-label, single-arm, phase 1/2a study; the selected patients had chronic motor deficits between 6 and 60 months after nonhemorrhagic stroke. SB623 cells were administered to the target sites surrounding the subcortical stroke region using MRI stereotactic image guidance. A total of 18 patients were treated with SB623 cells. All experienced at least 1 treatment-emergent adverse event (TEAE). No patients withdrew due to adverse events, and there were no dose-limiting toxicities or deaths. The most frequent TEAE was headache related to the surgical procedure (88.9%). Seven patients experienced 9 serious adverse events, which resolved without sequelae. In 16 patients who completed 24 months of treatment, statistically significant improvements from baseline (mean) at 24 months were reported for the European Stroke Scale (ESS) score, 5.7 (95% CI 1.4-10.1, p < 0.05); National Institutes of Health Stroke Scale (NIHSS) score, -2.1 (95% CI -3.3 to -1.0, p < 0.01), Fugl-Meyer (F-M) total score, 19.4 (95% CI 9.9-29.0, p < 0.01); and F-M motor scale score, 10.4 (95% CI 4.0-16.7, p < 0.01). Measures of efficacy reached plateau by 12 months with no decline thereafter. There were no statistically significant changes in the modified Rankin Scale score. The size of transient lesions detected by T2-weighted FLAIR imaging in the ipsilateral cortex at weeks 1-2 postimplantation significantly correlated with improvement in ESS (0.619, p < 0.05) and NIHSS (-0.735, p < 0.01) scores at 24 months. In this completed 2-year phase 1/2a study, implantation of SB623 cells in patients with stable chronic stroke was safe and was accompanied by improvements in clinical outcomes.Clinical trial registration no.: NCT01287936 (clinicaltrials.gov).

Current status of development for regenerative cell therapy, SB623

SanBio Co., Ltd. is developing regenerative medicine, SB623. SB623 secretes neurotrophic and growth factors, and can possibly show benefit in repair of the damaged brain after stroke. An open-label, single-arm phase I/IIa clinical study was conducted with 18 chronic ischemic stroke patients in the United States to evaluate the safety and clinical outcomes of surgical transplantation of SB623. Clinical evaluation for a one year follow-up period showed significant improvements with all mean scores on the European Stroke Scale, the National Institute of Health Stroke Scale, and on the basis of fugl-Meyer Assessment. All patients experienced neither side effects nor serious treatment-emergent adverse events related to cell treatments. These results suggest that SB623 cell transplantation is safe and effective for treating chronic ischemic stroke. Currently we are conducting clinical studies in Japan and the US, and are accelerating clinical development to provide our cells to patients under new regulation of regenerative medical product in Japan.

Abstract TP440: Elevated Plasma Level of Soluble Form of RAGE in Ischemic Stroke Patients With Vascular Cognitive Impairment

Background / Purpose: Little is known about the role of receptor for advanced glycation end products (RAGE) -mediated signaling in the development of vascular cognitive impairment (VCI). The study aimed to investigate the associations of various RAGE signaling related plasma biomarkers and the development of VCI in chronic ischemic stroke (IS) patients. Methods: This cross-sectional study recruited patients with IS at an university medical center stroke clinic. VCI was defined as the scale of Clinical Dementia Ranking (CDR) ≥1. Standard enzyme-linked immunosorbent assay was used to measure the plasma concentration of soluble form of RAGE (sRAGE), endogenous soluble form of RAGE (esRAGE), high mobility group box 1 (HMGB1) and matrix metallopeptidase 9 (MMP9) in IS patients with and without VCI. Results: Between November 2014 to October 2015, a total of 172 IS patients (mean age 72.1±7.5 years, 64.5% male) were recruited, including 73 with CDR=0, 63 with CDR=0.5 and 36 with CDR ≥1. In univariate analysis, IS patients with VCI were older, and had more diabetes mellitus, fewer atrial fibrillation, and higher post-stroke modified Rankin Scales than those without. Plasma levels of sRAGE and esRAGE, but not HMGB1 or MMP9 were significantly higher in IS patients with VCI than those without (1.44±1.29 versus 1.03±0.48 and 0.39±0.40 versus 0.24±0.13 ng/ml, both p&lt;0.01). Importantly, both parameters remained independent after adjustment for clinical variables (OR 2.683, p=0.013 and OR 39.192, p=0.006, respectively). Conclusion: Among IS patients, plasma levels of both sRAGE and esRAGE were elevated in those with VCI.

Abstract TP138: Repeated Bilateral Multifocal Cortical Magnetic Stimulation with a New Wearable Transcranial Stimulator in Chronic Ischemic Stroke

Introduction: Repetitive transcranial magnetic stimulation (rTMS) treatment of ipsilesional (IL) or contralesional (CL) cortex combined with occupational/physical therapy (OT/PT) shows significant promise in chronic ischemic stroke (CIS). Here we describe a multifocal cortical magnetic stimulation protocol with a new wearable device called transcranial rotating permanent magnet stimulator (TRPMS) for a pilot clinical trial in CIS, and present preliminary results in one patient. Hypothesis: Simultaneous repeated excitatory and inhibitory stimulations of IL and CL cortical sites, respectively cause perilesional functional cortical reorganization with recovery of motor function in CIS. Methods: After informed consent, we treated a 58-year old male patient with a right middle cerebral artery thromboembolic infarct causing left sided hemiparesis. At the start of TRPMS treatment 19 months after the stroke he had a stable baseline on motor function tests. The treatment consisted of 4 two-week sessions (with intervening one-week rest periods) of daily (on week days) 40 min TRPMS stimulation (5 Hz, 25 ms pulse duration at 4 perilesional cortical sites, and 0.2 Hz, 100 ms pulse duration at 2 CL primary motor cortical sites) accompanied by OT/PT. Pretreatment, posttreatment and follow-up assessments were functional magnetic resonance imaging (fMRI) during attempted gripping movements, and grip strength, gait speed and Fugl-Meyer (FM) scale testing. Results: After the 2 nd treatment session movement-related fMRI showed increasing levels of neural activation of the stimulated intact cortex surrounding the lesion. Grip strength of the affected hand increased ~2.5 fold. Gait speed increased by ~15%. Left lower extremity motor function and sensation measures on the FM scale showed sustained increase by ~17% and ~30%, respectively. These changes persisted above the pretreatment levels at the 3-month follow-up. There were no adverse effects. Conclusions: These findings suggest that the new TRPMS protocol might bring about some degree of functional cortical reorganization and motor recovery in CIS. We have therefore launched a randomized double-blind sham treatment-controlled clinical trial involving a four-week TRPMS treatment in 30 CIS patients.

No Change in Brain-Derived Neurotrophic Factor Levels Following a Single Session of Light to-Moderate Intensity Walk in Chronic Stroke Patients

Background: Many studies show the beneficial effects of overground gait training in stroke patients. However, it is not know whether it is able to induce changes in brain-derived neurotrophic factor (BDNF) levels, which could positively influence neurophysiological mechanisms. Objective: To evaluate the effect of a single session of light-to-moderate intensity walk on BDNF serum levels and its precursors (proBDNF) in chronic ischemic stroke patients. Methods: Patients were asked to walk for 30 minutes in the target heart rate training zone (30-60% of maximal heart rate). Blood samples were collected immediately before and after a single session. Results: Fifteen individuals with 60.8 (7.7) years old participated of this study. There was no significant difference in proBDNF (p=0.573) and BDNF (p=0.563) serum levels between pre- and post-session. Conclusion: This study used light-to-moderate intensity because the goal is to approach the gait training in clinical setting. The lack of increase in BDNF levels can be explained by two reasons: the intensity zone of the heart rate selected during the session and not having a gradual increase in this intensity.

Paracrine Mechanisms of Intravenous Bone Marrow-Derived Mononuclear Stem Cells in Chronic Ischemic Stroke

Background: The emerging role of stem cell technology and transplantation has helped scientists to study their potential role in neural repair and regeneration. The fate of stem cells is determined by their niche, consisting of surrounding cells and the secreted trophic growth factors. This interim report evaluates the safety, feasibility and efficacy (if any) of bone marrow-derived mononuclear stem cells (BM-MNC) in chronic ischemic stroke by studying the release of serum vascular endothelial growth factor (VEGF) and brain-derived neurotrophic growth factor (BDNF). Methods: Twenty stroke patients and 20 age-matched healthy controls were recruited with the following inclusion criteria: 3 months to 1.5 years from the index event, Medical Research Council (MRC) grade of hand muscles of at least 2, Brunnstrom stage 2-5, conscious, and comprehendible. They were randomized to one group receiving autologous BM-MNC (mean 60-70 million) and to another group receiving saline infusion (placebo). All patients were administered a neuromotor rehabilitation regime for 8 weeks. Clinical assessments [Fugl Meyer scale (FM), modified Barthel index (mBI), MRC grade, Ashworth tone scale] were carried out and serum VEGF and BDNF levels were assessed at baseline and at 8 weeks. Results: No serious adverse events were observed during the study. There was no statistically significant clinical improvement between the groups (FM: 95% CI 15.2-5.35, p = 0.25; mBI: 95% CI 14.3-4.5, p = 0.31). VEGF and BDNF expression was found to be greater in group 1 compared to group 2 (VEGF: 442.1 vs. 400.3 pg/ml, p = 0.67; BDNF: 21.3 vs. 19.5 ng/ml) without any statistically significant difference. Conclusion: Autologous mononuclear stem cell infusion is safe and tolerable by chronic ischemic stroke patients. The released growth factors (VEGF and BDNF) in the microenvironment could be due to the paracrine hypothesis of stem cell niche and neurorehabilitation regime.

ID 29 – Focal lesion on the hand knob re-localizes motor function laterally compared to the unaffected hemisphere

Objective To evaluate the differences in cortical muscle representations between affected and unaffected hemispheres in stroke patients using navigated transcranial magnetic stimulation (nTMS). Methods Eight right-handed chronic ischemic stroke patients (2 females, age range: 48–68 years) who had an M1 hand knob localized lesion (2 left hemisphere, 6 right hemisphere, at least 2 years from stroke) were studied. Single-pulse nTMS was applied with a stimulation intensity of 110% of the resting motor threshold to map the functional cortical representation of APB muscle of affected and unaffected hemisphere. Differences in center of gravities (CoGs) obtained in cortical areas producing responses exceeding 50 μ V in amplitude were assessed using paired t-test. Results CoGs on the affected hemisphere were more lateral compared to the unaffected hemisphere (mean difference 0.9 cm, p = 0.030), no differences were observed in anterior-posterior direction ( p = 0.190). The representation areas between affected and unaffected hemisphere were not different form each other ( p = 0.577). Conclusions The cortical muscle representation of the affected hemisphere had changed, which can be seen as more laterally localized CoG compared to the unaffected hemisphere. Key message Focal lesion on the motor functional hand area causes re-localization of the representation, while the representation size is unaffected.

ID 30 – Influence of M1 hand knob ischemic stroke on motor activation: An fMRI study in chronic stage

Objective To evaluate whether stroke lesion focused on the primary motor cortex hand knob re-localizes the hand motor area in the affected hemisphere. Methods The study included 8 right-handed chronic ischemic stroke patients (2 females, age range: 48–68 years) with hand knob localized lesion (2 left hemisphere, 6 right hemisphere, at least 2 years from stroke). Block-design fMRI was performed using a 3T MR scanner during finger tapping task to both hemispheres. For the analysis, images with left hemisphere lesions were flipped. Differences between affected and unaffected hemispheres were tested with a paired t-test using a threshold of p T = 4.79), uncorrected for multiple comparisons. Results Significantly reduced motor activation in the affected hemisphere versus unaffected hemisphere was observed in the posterior part of precentral gyrus (hand-knob), pars opercularis and pars triangularis of the inferior frontal gyrus, inferior parietal cortex, intraparietal sulcus and lobule VI in cerebellum. Conclusions Reduction in the hand motor activation was observed in M1 in the affected hemisphere. Key message fMRI is capable to detect abnormal motor activation after focal stroke on hand knob area.

Cerebral localization of impaired phonological retrieval during rhyme judgment.

Computation of a prearticulatory phonological representation (phonological access, or phonological retrieval) is an essential process in speech production whose neural localization is not clear. This study combined a specific behavioral measure of phonological access and multivariate voxel-based lesion-symptom mapping (VLSM) in a series of left hemisphere stroke patients to identify brain regions critical for this process. Phonological access was assessed in 40 chronic ischemic stroke patients using a silent rhyming task to avoid confounds with motor planning and articulation deficits. Additional covariates were incorporated in the VLSM analysis to control for orthographic and working memory demands of the rhyming task, and for age, education, and total lesion volume. The resulting t statistic maps were thresholded at voxelwise p < 0.001 and cluster-corrected at a familywise error of p < 0.05. Phonological access impairment was correlated with damage to a focal region of cortex and white matter caudal to the posterior sylvian fissure, which included the posterior supramarginal gyrus and adjacent anterior angular gyrus, planum temporale, and posterior superior temporal gyrus. No correlation was observed with Broca's area, insula, or sensorimotor cortex. An additional VLSM showed no correlation between damage in this posterior perisylvian region and spoken word comprehension. This is the first demonstration of a specific lesion correlate for phonological access impairment. Although this posterior perisylvian region overlaps with some versions of the classical Wernicke area, the present results demonstrate its involvement in prearticulatory phonological production rather than speech perception or lexical-semantic processes.

Abstract TP401: Inflated Expectations about Stem Cell Therapy in Patients With Chronic Stroke

Introduction: Stem cell therapy (SCT) has been proposed for the treatment of neurological disorders. Although there isinsufficient clinical evidence to support its efficacy, unproven SCTs are being performed worldwide. Hypothesis: In this study, we investigated the perspectives and expectations of chronic ischemic stroke patients and physicians about SCTs. Methods: A total of 250 chronic ischemic stroke patients were interviewed at 4 hospitals. Structured open and closed questions about SCT for chronic stroke were asked by trained interviewers using the conventional in-person method. In addition, 250 stroke-related physicians were randomly interviewed via an e-mail questionnaire. Results: Of the 250 patients (mean 63 years, 70% male), 121 (46%) responded that they wanted to receive SCT in spite of its unknown side effects. Around 60% of the patients anticipated physical, emotional, and psychological improvement after SCT, and 158 (63%) believed that SCT might prevent strokes. However, physicians had much lower expectations about the effectiveness of SCTs, which was not in line with patient expectations. Multivariate analysis revealed that male gender (OR: 2.00, 95% CI: 1.10-3.64), longer disease duration (OR: 1.01, 95% CI:1.00-1.02), higher modified Rankin Scale score (OR: 1.30, 95% CI 1.06-1.60), and familiarity with stem cells (OR: 1.86, 95% CI: 1.10-3.15) were independently associated with wanting SCT. The major source of information about SCT was television (68%), and the most reliable source was physicians (49%). Conclusion: Patients have unfounded expectations that SCT will improve their functioning. Considering our finding that the major source of information on stem cells is media channels but not the physician, to decrease patients’ inappropriate exposure, doctors should make more effort to educate patients using mass media with accurate information.

A Novel Useful Tool of Computerized Touch Panel–Type Screening Test for Evaluating Cognitive Function of Chronic Ischemic Stroke Patients

Cognitive and affective impairments are important non-motor features of ischemic stroke (IS) related to white-matter hyperintensity, including periventricular hyperintensity (PVH). To confirm the usefulness of a novel computerized touch panel-type screening test, we investigated cognitive and affective functioning among 142 IS patients and 105 age-and gender-matched normal control subjects. Assessment using the mini-mental state examination, Hasegawa Dementia Scale-Revised, and frontal assessment battery revealed reduced cognitive function in IS patients, with the most severe reduction exhibited by cardiogenic embolism patients, followed by lacunar infarction patients, and atherothrombotic infarction patients. Our novel touch panel screening test revealed a similar pattern of results. In addition, PVH grading, classified using Fazekas' magnetic resonance imaging method, was also correlated with cognitive decline and touch panel screening test performance. In contrast, affective function, assessed with the 15-item Geriatric Depression Scale, vitality index, and apathy scale, was not significantly decreased in IS, and did not correlate with touch panel screening test results or PVH, although the number of microbleeds was correlated with apathy scale results. The present findings revealed that IS and PVH grading were significantly correlated with decline in general cognitive status (mini-mental state examination and Hasegawa Dementia Scale-Revised) and frontal lobe function (frontal assessment battery). Performance on all touch panel screening tests was correlated with IS and PVH grading, but was largely independent of depression or apathy. Touch panel screening tests were easily understood and performed by almost all patients with mild cognitive and motor dysfunction, due to visually clear images andsimple methods not involving detailed manual-handling tasks such as writing. Touch panel screening tests may provide a useful tool for the early screening of cognitive function.

Autologous Intravenous Mononuclear Stem Cell Therapy in Chronic Ischemic Stroke

The regenerative potential of brain has led to emerging therapies that can cure clinico-motor deficits after neurological diseases. Bone marrow mononuclear cell therapy is a great hope to mankind as these cells are feasible, multipotent and aid in neurofunctional gains in Stroke patients. This study evaluates safety, feasibility and efficacy of autologous mononuclear (MNC) stem cell transplantation in patients with chronic ischemic stroke (CIS) using clinical scores and functional imaging (fMRI and DTI). Non randomised controlled observational study Study: Twenty four (n=24) CIS patients were recruited with the inclusion criteria as: 3 months-2years of stroke onset, hand muscle power (MRC grade) at least 2; Brunnstrom stage of recovery: II-IV; NIHSS of 4-15, comprehendible. Fugl Meyer, modified Barthel Index (mBI) and functional imaging parameters were used for assessment at baseline, 8 weeks and at 24 weeks. Twelve patients were administered with mean 54.6 million cells intravenously followed by 8 weeks of physiotherapy. Twelve patients served as controls. All patients were followed up at 24 weeks. The laboratory and radiological outcome measures were within normal limits in MNC group. Only mBI showed statistically significant improvement at 24 weeks (p<0.05) whereas the mean FM, MRC, Ashworth tone scores in the MNC group were high as compared to control group. There was an increased number of cluster activation of Brodmann areas BA 4, BA 6 post stem cell infusion compared to controls indicating neural plasticity. Cell therapy is safe and feasible which may facilitate restoration of function in CIS.

Poster 79 Robot-Assisted Hand Training Compared With Conventional Hand Therapy in Chronic Ischemic Stroke Patients: A Pilot Study

The purpose of this study was to examine functional outcomes of participants after completing a treatment program either with conventional therapy or a robotic hand device. CorrectionArchives of Physical Medicine and RehabilitationVol. 94Issue 1PreviewPoster 79 in the 2012 ACRM–ASNR Joint Educational Conference abstracts published in October contained an incomplete list of authors. (To view the full issue, please visit the Archives journal website at http://www.archives-pmr.org/issues .) The poster title and corrected author list appear below. We apologize for the errors. Full-Text PDF

Fantasies About Stem Cell Therapy in Chronic Ischemic Stroke Patients

Stem cell therapy (SCT) has been proposed for the treatment of neurological disorders. Although there is insufficient clinical evidence to support its efficacy, unproven SCTs are being performed worldwide. In this study, we investigated the perspectives and expectations of chronic ischemic stroke patients and physicians about SCTs. A total of 250 chronic ischemic stroke patients were interviewed at 4 hospitals. Structured open and closed questions about SCT for chronic stroke were asked by trained interviewers using the conventional in-person method. In addition, 250 stroke-related physicians were randomly interviewed via an e-mail questionnaire. Of the 250 patients (mean 63 years, 70% male), 121 (46%) responded that they wanted to receive SCT in spite of its unknown side effects. Around 60% of the patients anticipated physical, emotional, and psychological improvement after SCT, and 158 (63%) believed that SCT might prevent strokes. However, physicians had much lower expectations about the effectiveness of SCTs, which was not in line with patient expectations. Multivariate analysis revealed that the male gender [odds ratio (OR): 2.00, 95% confidence interval (CI): 1.10-3.64], longer disease duration (OR: 1.01, 95% CI: 1.00-1.02), higher modified Rankin Scale score (OR: 1.30, 95% CI: 1.06-1.60), and familiarity with stem cells (OR: 1.86, 95% CI: 1.10-3.15) were independently associated with wanting SCT. The major source of information about SCT was television (68%), and the most reliable source was physicians (49%). Patients have unfounded expectations that SCT will improve their functioning. Considering our finding that the major source of information on stem cells is media channels, but not the physician, to decrease patients' inappropriate exposure, doctors should make more effort to educate patients using mass media with accurate information.

70th Birthday symposium of Prof. Dr. Riederer: autologous adult stem cells in ischemic and traumatic CNS disorders

Ischemic and traumatic insults of the central nervous system both result in definite chronic disability, only to some extent responsive to rehabilitation. Recently, the application of autologous stem cells (fresh bone marrow-derived mononuclear cells including mesenchymal and hematopoietic stem cells) was suggested to provide a strategy to further improve neurological recovery in these disorders. During the acute phase, stem cells act mainly by neuroprotection with prevention of apoptosis, whereas during the chronic situation they provide neurorestoration by transdifferentiation and/or the secretion of neurotrophic factors. To reach these goals, in the acute phase, stem cells (10 million mononuclear cells per kg body weight) might be best applied intravenously, as during the first 7 days after the lesion, the blood-brain barrier permits passage of cells from the blood into the brain or the spinal cord. In the more chronic situation, though, those cells might be applied best intrathecally by lumbar puncture. Based on the reported results so far, it seems justified to develop well-designed clinical double-blind trials in chronic spinal cord injury and ischemic stroke patients, as efficacy and safety concerns might not be answered by preclinical studies.

Prevalence and Risk Factors of Peripheral Artery Disease in Elderly Chronic Ischemic Stroke Patients: A Study of a Single Geriatric Hospital

Results: Of the 96 patients, 55 (57.3%) had PAD (ABI<0.9) of which 6 patients (6.3%) had severe PAD (ABI<0.5) and 22 patients (22.9%) had bilateral PAD. PAD was more frequently observed in patients with diabetes (65% vs. 15%, p=0.001), hypercholesterolemia (65% vs. 15%, p<0.001), previous history of coronary artery disease (CAD) (25% vs. 5%, p=0.01) and recurrent ischemic stroke (36% vs. 12%, p=0.01). The means of the total cholesterol and blood urea nitrogen were higher in patients with PAD. From the results of the binary logistic regression analysis, presence of diabetes (odds ratio [OR], 4.740; p=0.026), hypercholesterolemia (OR, 18.991; p<0.001), previous history of CAD (OR, 7.579; p=0.038) and lower Korean version of Modified Barthel Index (OR, 0.971; p=0.009) were independent risk factors for PAD. Conclusion: PAD is frequently observed in elderly patients with chronic ischemic stroke. Measuring ABI to diagnose PAD and controlling risk factors may be beneficial in these patients seen at geriatric hospitals and centers.

Short- and long-term effect of rTMS on motor function recovery after ischemic stroke

This review discusses the clinical results that were obtained by applying rTMS in acute and chronic ischemic stroke patients. These studies included only the recovery of motor disability and dysphagia. In summary, two approaches have been used when employing rTMS as a potential therapy for the treatment of stroke. The most direct approach involves applying rTMS directly over the affected hemisphere in an attempt to increase excitability and plasticity of damaged circuits to improve motor function. The second approach has taken advantage of the concept of interhemispheric balance in which damage to the stroke hemisphere is exacerbated by increased inhibition from the intact non-stroke hemisphere. In this case, inhibitory rTMS is applied to the non-stroke hemisphere with the intention of reducing interhemispheric inhibition and restoring the balance of excitation between the motor cortices.The overall procedure remains to be optimized, in particular regarding the number of rTMS sessions, frequency and intensity of stimulation and the exact timing of rTMS application after stroke. Cortical stimulation is an effective method for improving functional recovery of acute and chronic stroke.

Platelet Aggregation and Recruitment with Aspirin-Clopidogrel Therapy

Background: Aspirin-clopidogrel combination therapy inhibits platelet aggregation. The effect on platelet recruitment is unknown. Methods: Thirty chronic ischemic stroke patients taking aspirin alone followed by aspirin-clopidogrel combined therapy had platelet reactivity tests performed over 3 months: ex vivo platelet aggregation, platelet recruitment and urinary 11-dehydro-thromboxane B₂ (11-dhTxB₂)excretion. Statistical analysis of variance compared platelet aggregation and recruitment between aspirin alone and aspirin-clopidogrel, and longitudinal regression analysis estimated platelet recruitment over time. Nonlinear mapping defined variable connections in each patient. Results: Statistically significant differences were found between aspirin alone and aspirin-clopidogrel for (1) adenosine-diphosphate- and collagen-induced platelet aggregation and maximum inhibition of platelet recruitment and (2) increasing inhibition of platelet recruitment over time. Urinary 11-dhTxB₂ excretion did not predict platelet aggregation response. Nonlinear mapping showed patient-unique variable interconnections. Conclusions: Platelet inhibition with aspirin-clopidogrel may increase over time, and future studies should focus on this finding in the context of vascular complications.