[A case of anti-acetylcholine receptor antibody-positive ocular myasthenia gravis with anti-titin antibody and anti-Kv1.4 antibody positive inflammatory myopathy].

An 84-year-old man was diagnosed with anti-acetylcholine receptor (AChR) antibody-positive ocular myasthenia gravis (OMG) at the age of 77 and received treatment. The patient was referred to our department with swelling and pain in his right upper arm, which had spread to other limbs. His serum anti-AChR antibody and creatine kinase levels were elevated, and MRI of the limbs displayed signal changes suggesting inflammation in the several muscles. Despite showing no sign of thymoma, he was positive for serum anti-titin and anti-Kv1.4 antibodies. We performed a muscle biopsy, which led to a diagnosis of inflammatory myopathy (IM). IM associated with OMG is relatively mild. Age-related immune dysregulation may cause both OMG and IM. Evaluation of disease activity with serum anti-AChR antibody levels, and assessment of prognosis with examining anti-striational antibodies are necessary for appropriate management of IM associated with MG.

[A patient with anti-myelin oligodendrocyte glycoprotein antibody-associated combined central and peripheral demyelination with anti-galactocerebroside and anti-GM1 antibodies].

A 48-year-old male was admitted to our hospital because of chronic progressive demyelination of the peripheral nerves of the upper limbs, as well as acute myelitis presenting with sensory disturbance from the left chest to the left leg. We established a diagnosis of combined central and peripheral demyelination (CCPD). The patient was positive for serum anti-myelin oligodendrocyte glycoprotein (MOG), anti-galactocerebroside IgG, and anti-GM1 IgG antibodies. Intravenous methylprednisolone therapy and plasma exchange improved myelitis, and the subsequent administration of oral prednisolone yielded a gradual improvement of the peripheral nerve damage with a mostly negative result for the antibodies. However, the patient experienced a relapse of radiculitis eight months later. Relapses of anti-MOG antibody-associated disease can provoke new immune reactions, leading to CCPD.

Theoretical morphological analysis of differential morphospace occupation patterns for terrestrial and aquatic gastropods.

Despite the morphological diversity of organisms, they only occupy a fraction of the theoretically possible spectrum (i.e., morphospace) and have been studied on several taxa. Such morphospace occupation patterns are formed through evolutionary processes under multiple constraints. In this study, we discovered a differential morphospace occupation pattern between terrestrial and aquatic gastropods and subsequently attempted to quantitatively understand these differences through morphospace analysis. These differential occupation patterns between terrestrial and aquatic species were observed in the morphospace of spire height and aperture inclination, including a bimodal distribution of shell height in terrestrial species alongside the absence of high-spired shells with high aperture inclination. Although terrestrial species were distributed along optimal lines of shell instability and shell hindrance to locomotion, aquatic species were distributed not only along this line but also within a suboptimal region of the low spire with low inclination. Based on numerical simulation and biometric analysis, here we propose the hypothesis that this difference was caused by the aquatic species being able to adopt a posture with the growth direction perpendicular to the substrate due to reduced functional demands. Our results provided an ultimate explanation for the differential occupation patterns between habitats alongside an overview of the morphospace.

TDP-43 regulates early-phase insulin secretion via CaV1.2-mediated exocytosis in islets.

TAR DNA-binding protein 43 kDa (TDP-43), encoded by TARDBP, is an RNA-binding protein, the nuclear depletion of which is the histopathological hallmark of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder affecting both upper and lower motor neurons. Besides motor symptoms, patients with ALS often develop nonneuronal signs including glucose intolerance, but the underlying pathomechanism is still controversial, i.e., whether it is impaired insulin secretion and/or insulin resistance. Here, we showed that ALS subjects reduced early-phase insulin secretion and that the nuclear localization of TDP-43 was lost in the islets of autopsied ALS pancreas. Loss of TDP-43 inhibited exocytosis by downregulating CaV1.2 calcium channels, thereby reducing early-phase insulin secretion in a cultured ß cell line (MIN6) and ß cell-specific Tardbp knockout mice. Overexpression of CaV1.2 restored early-phase insulin secretion in Tardbp knocked-down MIN6 cells. Our findings suggest that TDP-43 regulates cellular exocytosis mediated by L-type voltage-dependent calcium channels and thus plays an important role in the early phase of insulin secretion by pancreatic islets. Thus, nuclear loss of TDP-43 is implicated in not only the selective loss of motor neurons but also in glucose intolerance due to impaired insulin secretion at an early stage of ALS.

Efficacy and safety of leuprorelin acetate for subjects with spinal and bulbar muscular atrophy: pooled analyses of two randomized-controlled trials.

BACKGROUND: Spinal and bulbar muscular atrophy (SBMA) is an adult-onset, hereditary neuromuscular disease characterized by muscle atrophy, weakness, contraction fasciculation, and bulbar involvement. Although the causative gene, androgen receptor, has been identified, the development of novel therapeutics for SBMA is incomplete. In this study, the efficacy and safety of leuprorelin acetate administration for patients with SBMA, using the pooled data of two randomized-controlled trials, was studied. METHODS: Two randomized double-blinded studies (JASMITT-06DB and JASMITT-11DB) were done as multicentric, investigator-initiated clinical trials in Japan. In both studies, eligible patients were randomly assigned 1:1 to receive leuprorelin acetate administration once per 12 weeks for 48 weeks. The primary endpoint was the longitudinal change of pharyngeal barium residues from the baseline data measured with videofluorographic swallowing analyses. The pooled analysis plan was decided upon after the 06B study was finished and before the 11DB study began. RESULTS: The primary endpoint difference between the leuprorelin group and the placebo group was pharyngeal barium residue after initial swallowing, - 4.12% (95% CI, - 8.40-0.15; p = 0.058). The primary endpoint of this study does not reach significant results, although inter-group differences of pharyngeal barium residues after the initial swallowing indicated that leuprorelin acetate may be effective at each assessment point in both study groups. CONCLUSIONS: The efficacy of leuprorelin acetate for patients with SBMA was statistically similar in two randomized-controlled trials, and suggested that leuprorelin acetate may be effective and safe. Further investigations are needed to clarify the promising efficacy of the drug.

Hereditary Angioedema Type 1 with Recurrent Dizziness.

A 41-year-old woman presented with recurrent dizziness. After an attack of dizziness, she felt edematous sensations in her hands. However, according to photographs taken during the attack, the edema on the back of the patient's hands and fingers appeared mild. Laboratory examinations revealed a low C4 and C1 inhibitor (INH) activity. A direct sequencing analysis of C1INH revealed a pathogenic gene mutation. Based on these results, she was diagnosed with hereditary angioedema (HAE) type 1. These findings indicate that HAE can cause recurrent dizziness, and it should therefore be included in the differential diagnosis in patients with recurrent neurologic symptoms, even in the absence of severe edema.

[Parkinson's disease associated with SAPHO syndrome: a case report].

A 77-year-old woman with Parkinson's disease presented with left chest pain. Physical examination revealed tenderness at her second left sternocostal joint. There was no skin rash. Chest CT revealed hyperostosis of the sternocostal joint, and cervical MRI showed vertebral osteosclerosis and osteolysis. 99mTc-MDP bone scintigraphy showed an increased activity in the sternocostal joint and vertebral column. The patient was diagnosed with SAHPO syndrome according to the diagnostic criteria. Her chest pain was relieved after oral administration of nonsteroidal anti-inflammatory drugs. Although pain is a common non-motor symptom of Parkinson's disease, chest pain is relatively rare, according to a previous reports. When patients with Parkinson's disease complain of chest pain, physicians should make an appropriate differential diagnosis after excluding emergent cardiovascular disease. To the best of our knowledge, this is the first report of Parkinson's disease associated with SAPHO syndrome. The relationship between the two diseases is unclear. However, peripheral inflammation is known to exacerbate ongoing neuronal damage in neurodegenerative diseases, such as Parkinson's disease. Therefore, systemic inflammation of SAPHO syndrome may affect the disease course of Parkinson's disease.

Treatment with Creatine Monohydrate in Spinal and Bulbar Muscular Atrophy: Protocol for a Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Although spinal and bulbar muscular atrophy (SBMA) has been classified as a motor neuron disease, several reports have indicated the primary involvement of skeletal muscle in the pathogenesis of this devastating disease. Recent studies reported decreased intramuscular creatine levels in skeletal muscles in both patients with SBMA and transgenic mouse models of SBMA, which appears to contribute to muscle weakness. OBJECTIVE: The present study aimed to examine the efficacy and safety of oral creatine supplementation to improve motor function in patients with SBMA. METHODS: A randomized, double-blind, placebo-controlled, three-armed clinical trial was conducted to assess the safety and efficacy of creatine therapy in patients with SBMA. Patients with SBMA eligible for this study were assigned randomly in a 1:1:1 ratio to each group of placebo, 10 g, or 15 g daily dose of creatine monohydrate in a double-blind fashion. Participants took creatine or placebo orally 3 times a day for 8 weeks. Outcome measurements were results of neurological assessments, examinations, and questionnaires collected at baseline and at weeks 4, 8, and 16 after a washout period. The primary endpoint was the change in handgrip strength values from baseline to week 8. The secondary endpoints included the following: results of maximum voluntary isometric contraction tests of extremities; tongue pressure; results of the 15-foot timed walk test and the rise from bed test; modified quantitative myasthenia gravis score; respiratory function test results; activities of daily living assessed with the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale and the Spinal and Bulbar Muscular Atrophy Functional Rating Scale; skeletal muscle mass measured with dual-energy X-ray absorptiometry; urinary 8-hydroxydeoxyguanosine levels; and questionnaires examining the quality of life, swallowing function, and fatigue. RESULTS: Participant enrollment in the trial started from June 2014 and follow-up was completed in July 2015. The study is currently being analyzed. CONCLUSIONS: This is the first clinical trial evaluating creatine therapy in SBMA. Given that creatine serves as an energy source in skeletal muscles, recovery of intramuscular creatine concentration is expected to improve muscle strength. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry UMIN000012503; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000014611 (Archived by WebCite at http://www.webcitation.org/6xOlbPkg3).

Effectiveness of levodopa treatment for diabetic chorea with reduced striatal accumulation in dopamine transporter SPECT: a case report.

We report the case of a 77-year-old woman with diabetic chorea, which presented as hemiballism of the right limbs. Initial blood examination revealed that sugar and hemoglobin A1c levels were 732 mg/dl and 12.2%, respectively. Thus, a diagnosis of hyperglycemic hyperosmolar syndrome was made at a previous hospital. Ballism of the right limbs developed after 10 days and progressively worsened. After a month, the patient was admitted to our hospital. Brain MRI (axial T1-weighted imaging) revealed a high-signal-intensity area in the left striatum. Dopamine transporter SPECT demonstrated reduced 123I-ioflupane binding in the bilateral striatum with left side predominance. Although haloperidol and risperidone were ineffective for her involuntary movement, chlorpromazine had a little effect. Levodopa and gabapentin combination treatments were effective in decreasing the symptoms. It was considered that dopamine antagonist was the medical treatment for diabetic chorea and that levodopa could worsen neurological symptoms such as chorea-ballism. However, in our case, levodopa treatment was effective.

Swallowing markers in spinal and bulbar muscular atrophy.

OBJECTIVE: We examined the characteristics of dysphagia in spinal and bulbar muscular atrophy, a hereditary neuromuscular disease causing weakness of limb, facial, and oropharyngeal muscles via a videofluoroscopic swallowing study, and investigated the plausibility of using these outcome measures for quantitative analysis. METHODS: A videofluoroscopic swallowing study was performed on 111 consecutive patients with genetically confirmed spinal and bulbar muscular atrophy and 53 age- and sex-matched healthy controls. Swallowing of 3-mL liquid barium was analyzed by the Logemann's Videofluorographic Examination of Swallowing worksheet. RESULTS: Of more than 40 radiographic findings, the most pertinent abnormal findings in patients with spinal and bulbar muscular atrophy, included vallecular residue after swallow (residue just behind the tongue base), nasal penetration, and insufficient tongue movement (P < 0.001 for each) compared with healthy controls. Quantitative analyses showed that pharyngeal residue after initial swallowing, oral residue after initial swallowing, multiple swallowing sessions, and the penetration-aspiration scale were significantly worse in these patients (P ≤ 0.005 for each) than in controls. In patients with spinal and bulbar muscular atrophy, laryngeal penetration was observed more frequently in those without subjective dysphagia. INTERPRETATION: Dysphagia of spinal and bulbar muscular atrophy was characterized by impaired tongue movement in the oral phase and nasal penetration followed by pharyngeal residues, which resulted in multiple swallowing sessions and laryngeal penetration. Although major limitations of reproducibility and radiation exposure still exist with videofluoroscopy, pharyngeal residue after initial swallowing and the penetration-aspiration scale might serve as potential outcome measures in clinical studies.

Correlation of insulin resistance and motor function in spinal and bulbar muscular atrophy.

This study aimed to evaluate various metabolic parameters in patients with spinal and bulbar muscular atrophy (SBMA), to investigate the association between those indices and disease severity, and to explore the underlying molecular pathogenesis. We compared the degree of obesity, metabolic parameters, and blood pressure in 55 genetically confirmed SBMA patients against those in 483 age- and sex-matched healthy control. In SBMA patients, we investigated the correlation between these factors and motor functional indices. SBMA patients had lower body mass index, blood glucose, and Hemoglobin A1c, but higher blood pressure, homeostasis model assessment of insulin resistance (HOMA-IR, a marker of insulin resistance), total cholesterol, and adiponectin levels than the control subjects. There were no differences in visceral fat areas, high-density lipoprotein-cholesterol (HDL-C), or triglyceride levels in two groups. Revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R) correlated positively with HDL-C, but negatively with HOMA-IR. Through stepwise multiple regression analysis, we identified HOMA-IR as a significant metabolic determinant of ALSFRS-R. In biochemical analysis, we found that decreased expressions of insulin receptors, insulin receptor substrate-1 and insulin receptor-ß, in autopsied muscles and fibroblasts of SBMA patients. This study demonstrates that SBMA patients have insulin resistance, which is associated with the disease severity. The expressions of insulin receptors are attenuated in the skeletal muscle of SBMA, providing a possible pathomechanism of metabolic alterations. These findings suggested that insulin resistance is a metabolic index reflecting disease severity and pathogenesis as well as a potential therapeutic target for SBMA.

Impaired muscle uptake of creatine in spinal and bulbar muscular atrophy.

OBJECTIVE: The aim of this study was to explore the pathomechanism underlying the reduction of serum creatinine (Cr) concentrations in spinal and bulbar muscular atrophy (SBMA). METHODS: We evaluated blood chemistries, motor function, and muscle mass measured by dual-energy X-ray absorptiometry in male subjects with SBMA (n = 65), amyotrophic lateral sclerosis (ALS; n = 27), and healthy controls (n = 25). We also examined the intramuscular concentrations of creatine, a precursor of Cr, as well as the protein and mRNA expression levels of the creatine transporter (SLC6A8) in autopsy specimens derived from subjects who had SBMA and ALS and disease controls. Furthermore, we measured the mRNA expression levels of SLC6A8 in cultured muscle cells (C2C12) transfected with the polyglutamine-expanded androgen receptor (AR-97Q). RESULTS: Serum Cr concentrations were significantly lower in subjects with SBMA than in those with ALS (P < 0.001), despite similar muscle mass values. Intramuscular creatine concentrations were also lower in with the autopsied specimen of SBMA subjects than in those with ALS subjects (P = 0.018). Moreover, the protein and mRNA expression levels of muscle SLC6A8 were suppressed in subjects with SBMA. The mRNA levels of SLC6A8 were also suppressed in C2C12 cells bearing AR-97Q. INTERPRETATION: These results suggest that low serum Cr concentration in subjects with SBMA is caused by impaired muscle uptake of creatine in addition to being caused by neurogenic atrophy. Given that creatine serves as an energy source in skeletal muscle, increasing muscle creatine uptake is a possible therapeutic approach for treating SBMA.

Head Lift Exercise Improves Swallowing Dysfunction in Spinal and Bulbar Muscular Atrophy.

BACKGROUND: Dysphagia due to bulbar involvement is a major symptom of patients with spinal and bulbar muscular atrophy (SBMA). The aim of this pilot study was to test the efficacy and safety of the head lift exercise for swallowing dysfunction in SBMA. METHODS: We enrolled 6 subjects with genetically confirmed SBMA and instructed them to perform the head lift exercise for 6 weeks. The efficacy outcome measures were the changes from baseline in tongue pressure, the scores of swallowing functional questionnaires, and the motor functional scales and parameters of videofluorography (VF). RESULTS: All subjects completed the study and no major adverse effects were recorded. Tongue pressure significantly increased by 19.2 ± 0.15% (p < 0.05) after the 6-week head lift exercise. The scores for oral dysphagia also improved, although there was no significant change in VF parameters or other variables examined pre- and post-exercise. CONCLUSION: Our findings suggested that the head lift exercise may improve swallowing dysfunction, particularly tongue pressure, in SBMA.

A functional scale for spinal and bulbar muscular atrophy: Cross-sectional and longitudinal study.

We aimed to develop, validate, and evaluate a disease-specific outcome measure for SBMA: the Spinal and Bulbar Muscular Atrophy Functional Rating Scale (SBMAFRS). We examined the Japanese version (SBMAFRS-J) in 80 Japanese SBMA subjects to evaluate its validity and reliability. We then assessed this scale longitudinally in 41 additional SBMA subjects. The English version (SBMAFRS-E) was also tested in 15 US subjects. The total score of the SBMAFRS-J was distributed normally without an extreme ceiling or floor effect. For SBMAFRS-J, the high intra- and inter-rater agreement was confirmed (intra-class correlation coefficients [ICCs] 0.910 and 0.797, respectively), and internal consistency was satisfactory (Cronbach's alpha 0.700-0.822). In addition, SBMAFRS-J demonstrated concurrent, convergent, and discriminant validity, except for the respiratory subscale. The inter-rater reliability and internal consistency of SBMAFRS-E were also satisfactory. Longitudinally, SBMAFRS-J showed a higher sensitivity to disease progression than the existing clinical measures. In conclusion, we developed and validated a disease-specific functional rating scale for SBMA in both Japanese and English versions, although it needs to be re-assessed in interventional studies with a larger sample size including English speaking subjects.

Brugada syndrome in spinal and bulbar muscular atrophy.

OBJECTIVE: The aim of this study was to clarify myocardial involvement and its clinical implications in subjects with spinal and bulbar muscular atrophy (SBMA), a neuromuscular disease affecting both neuronal and nonneuronal tissues. METHODS: Two independent cardiologists evaluated ECGs from a total of 144 consecutive subjects with SBMA. We performed immunohistochemical, immunoblot, and quantitative real-time PCR analyses of autopsied myocardium. RESULTS: Abnormal ECGs were detected in 70 (48.6%) of 144 subjects. The most frequent findings were ST-segment abnormalities in V1-3 (19.4%), followed by ST-segment abnormalities in V5-6 (18.1%). We detected Brugada-type ECGs in 17 of 28 subjects with ST-segment abnormalities in V1-3. Of those, one subject presented with syncope that required an implantable cardioverter defibrillator and led to eventual sudden death, and another subject also died suddenly. No subjects with Brugada-type ECGs had mutations in SCN5A, CACNA1C, or CACNB2 genes. In autopsied cases, we detected nuclear accumulation of the mutant androgen receptor protein and decreased expression levels of SCN5A in the myocardium. CONCLUSIONS: Subjects with SBMA often show Brugada-type ECG. The accumulation of the pathogenic androgen receptor may have a role in the myocardial involvement in SBMA.

Tongue pressure as a novel biomarker of spinal and bulbar muscular atrophy.

OBJECTIVE: This study aimed to explore the reliability and validity of tongue pressure measurement as a quantitative evaluation of swallowing function in patients with spinal and bulbar muscular atrophy (SBMA). METHODS: This study enrolled 47 genetically confirmed patients with SBMA and 38 age- and sex-matched healthy controls. In both groups we measured tongue pressure using an intraoral pressure probe and assessed questionnaires that evaluated swallowing functions. We then analyzed the relationship between tongue pressure, functional scales, and the muscle weakness of other regions. RESULTS: Levels of tongue pressure were decreased in patients with SBMA within 3 years from the onset of the disease compared to healthy controls (SBMA 15.3 ± 6.4 kPa; healthy controls 37.3 ± 9.6 kPa; p < 0.001). Test-retest analysis showed a high reliability in patients with SBMA (intraclass correlation coefficient = 0.986). Tongue pressure showed a strong correlation with bulbar-related functional scales. Decrease of tongue pressure was detected in patients who reported no subjective dysphagia, and repetition of swallowing compensated for tongue weakness in such subjects. In patients with SBMA, tongue pressure more strongly correlates with the strength of pharyngeal, neck, and upper limb musculatures than with that of the lower limbs. CONCLUSION: Tongue pressure measurement is reliable and reflects swallowing function in patients with SBMA. The muscle strength of the tongue appears to decrease in SBMA before the awareness of subjective dysphagia, suggesting that tongue pressure measurement is a novel biomarker of SBMA and is applicable to early-stage detection.

Distinct acoustic features in spinal and bulbar muscular atrophy patients with laryngospasm.

OBJECTIVE: Laryngospasm is a sudden onset of transient respiratory difficulty that is perceived as life-threatening by patients with spinal and bulbar muscular atrophy (SBMA). The purpose of the study was to analyze the voice characteristics of SBMA patients with laryngospasm using acoustic voice analysis. METHODS: Acoustic measurements were obtained from 39 consecutive Japanese patients with genetically confirmed SBMA. A comparison was made between the acoustic voice profiles of 16 patients with laryngospasm and 23 patients without laryngospasm within 6 months before the evaluation. Computerized acoustic analysis was performed for a prolonged vowel (/a:/) using the Multi-Dimensional Voice Program (MDVP). RESULTS: SBMA patients with laryngospasm had smaller fluctuations of vocal fold vibration and the turbulent noise component, indicating stronger vocal fold closure than in those without laryngospasm. Receiver operating characteristic curve analysis showed that the noise-to-harmonic ratio, which globally measures the noise components of voice, is the most useful acoustic parameter to distinguish laryngospasm (area under the curve = 0.767, p = 0.007). CONCLUSIONS: The smaller noise component in patients with laryngospasm suggests that the vocal folds of these patients are more adducted during phonation than those of the patients without laryngospasm, even in the absence of laryngospasm. Quantitative laryngeal analysis using the MDVP helps to detect laryngeal dysfunction and provides physiological insight into the pathophysiology of laryngospasm in SBMA.

Secondary prevention of new vascular events with lifestyle intervention in patients with noncardioembolic mild ischemic stroke: a single-center randomized controlled trial.

BACKGROUND: Lifestyle modification is associated with a substantially decreased risk of cardiovascular events. However, the role of lifestyle intervention for secondary prevention in patients with noncardioembolic ischemic stroke is inadequately defined. We assessed the hypothesis that lifestyle intervention can reduce the onset of new vascular events in patients with noncardioembolic mild ischemic stroke. METHODS: We conducted an observer-blind randomized controlled trial that enrolled 70 patients (48 men, mean age 63.5 years) with acute noncardioembolic mild ischemic stroke. The patients were allocated in equal numbers to a lifestyle intervention group or a control group. We performed lifestyle interventions, which comprised exercise training, salt restriction and nutrition advice for 24 weeks. Then all patients were prospectively followed up for occurrence of the primary endpoints, including hospitalization due to stroke recurrence and the onset of other vascular events. We also evaluated systolic blood pressure (SBP) at the clinic and at home, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), hemoglobin A1c (HbA1c) and high-sensitivity C-reactive protein (hs-CRP) to compare the efficacy of the lifestyle interventions. RESULTS: This trial was terminated earlier than expected because of the prespecified early stopping rule for efficacy. After the 24-week intervention period, the intervention group showed a significant increase in daily physical activity and a significant decrease in salt intake (physical activity, p = 0.012; salt intake, p < 0.001), with a significant difference between the randomized groups (physical activity, p < 0.001; salt intake, p = 0.018). Similarly, blood pressure was decreased and the HDL-C levels were increased in the intervention group (SBP, p < 0.001; HDL-C, p = 0.018), with significant differences between the randomized groups (SBP, p < 0.001; HDL-C, p = 0.022). In contrast, LDL-C, HbA1c and hs-CRP tended to decrease in the intervention group, but this decrease did not achieve significance. After a median follow-up period of 2.9 years, 12 patients allocated to the control group and 1 patient in the lifestyle intervention group experienced at least 1 vascular event. A sequential plans analysis indicated the superiority of the lifestyle intervention in interim analysis. Kaplan-Meier survival curves after the log-rank test showed a significant prognostic difference between the randomized groups (p = 0.005). CONCLUSIONS: Lifestyle intervention with appropriate medication is beneficial for reducing the incidence of new vascular events and improving vascular risk factors in patients with noncardioembolic mild ischemic stroke.

Recurrence risk after noncardioembolic mild ischemic stroke in a Japanese population.

BACKGROUND AND PURPOSE: This study aimed to identify the recurrence rate and risk factors or clinical variables predictive of vascular events after mild ischemic stroke (IS). METHODS: From December 2006 to September 2007, patients with acute IS with a modified Rankin Scale of 0∼1 were consecutively enrolled in this study. Variables including sex, family history of vascular disease, age, height, weight, stroke subtype, blood pressure, lipid profile, fasting glucose, HbA1c, smoking, alcohol consumption, exercise habits, waist circumference, ankle-brachial pressure index, salt intake and physical activity were assessed. The primary outcome was stroke recurrence or other vascular events such as myocardial infarction, angina pectoris, and peripheral artery disease. Survival curves were calculated by Kaplan-Meier survival analysis, and hazard ratios for recurrence were determined by univariate and multivariate Cox proportional hazards regression models. RESULTS: A total of 102 mild IS patients (78 men and 24 women, mean age 64 years) were successfully followed for 3 years. Of those 102 patients, 25 (24.5%) had stroke recurrence, and 4 (3.9%) had a coronary event. Among the variables studied, abnormal ankle-brachial pressure index, metabolic syndrome, stroke subtypes, salt intake and poor lifestyle management were significant independent predictors of stroke recurrence or cardiovascular events. CONCLUSIONS: In mild IS patients within 3 years after onset, not only pathophysiological factors but also lifestyle factors can aid in the identification of patients at high risk for recurrence.