Prothrombotic abnormalities in childhood ischaemic stroke

Childhood ischaemic stroke, incorporating arterial ischaemic stroke and cerebral sinus venous thrombosis, is associated with significant morbidity and mortality in children. The majority of cases in children present with well-recognised risk factors.The appreciation of the role prothrombotic abnormalities have in disease states is developing rapidly. Prothrombotic abnormalities are abnormalities of the coagulation system, fibrinolytic system, endothelial cells or platelets that lead to a reduced threshold for pathological thrombus formation. Our understanding of the role of prothrombotic abnormalities in childhood ischaemic stroke is increasing and has a direct bearing on the development of effective management and prevention strategies.We provide a brief background of prothrombotic abnormalities and review the available literature on prothrombotic markers in childhood ischaemic stroke. Overall, prothrombotic abnormalities have been identified in 20-50% of children presenting with AIS and 33-99% of children with cerebral sinus venous thrombosis. There appear to be a number of associations emerging including an increased frequency of factor V Leiden mutation, elevated lipoprotein (a), protein C deficiency and antiphospholipid antibodies in children presenting with arterial ischaemic stroke. The pathogenic role of prothrombotic abnormalities as predisposing to initial and recurrent childhood ischaemic stroke is becoming increasingly evident. The impact on treatment, however, will only be clarified with carefully designed, multi-institutional prospective studies.     

Factor XIII A subunit Val34Leu polymorphism in patients suffering atherothrombotic ischemic stroke

Introduction

Factor XIII (FXIII) is a key regulator of fibrinolysis and clot firmness. Val34Leu polymorphism of its potentially active A subunit (FXIII-A) leads to faster activation of FXIII, influences clot structure and provides a moderate protection against coronary artery disease. The effect of FXIII A subunit (FXIII-A) Val34Leu polymorphism on the risk of ischemic stroke (IS) has been investigated in a few studies with contradictory results. In spite of their fundamental difference in pathogenesis and hemostatic pathomechanism, only four small studies investigated the effect of FXIII-A Val34Leu polymorphism on the risk of atherothrombotic IS (AIS) separately from cardioembolic IS. Gender specific effect of the polymorphism on the risk of AIS has not been explored. In the present study we investigated the effect of FXIII-A Val34Leu polymorphism on the risk of AIS on a large patient population.

Materials and methods

A population control group of 1,146 randomly selected individuals, 496 patients surviving AIS and their age and sex-matched controls selected from the population control group were included in the study. FXIII-A Val34Leu genotype was determined on DNA samples, obtained from peripheral blood leukocytes, by fluorescence resonance energy transfer detection using melting curve analysis.

Results

Neither sex nor age affected the distribution of FXIII-A Val34Leu genotypes in population control group. No association was revealed between the risk of AIS and FXIII-A Leu34 carriership and homozygous or heterozygous presentation of Leu34 allele in either gender.

Conclusion

FXIII-A Val34Leu polymorphism fails to influence the risk of AIS.     

Characteristics and clinical correlates of restless legs syndrome in schizophrenia

OBJECTIVE: The cause of restless legs syndrome (RLS) has not yet been ascertained, but one of the most promising theories involves dopaminergic deficiency. In accordance with this theory, we assumed that the prevalence of RLS would be higher among schizophrenics treated with antipsychotics than in the normal population. The purpose of this study was to establish the prevalence, characteristics, and clinical correlates of RLS in schizophrenic patients undergoing treatment with antipsychotics. METHODS: A total of 182 hospitalized schizophrenic patients and 108 age- and sex-matched normal controls were enrolled. The presence of RLS and its severity were assessed using the International Restless Legs Syndrome Study Group (IRLSSG) diagnostic criteria and the IRLSSG rating scale, respectively. The Athens Insomnia Scale (AIS), Brief Psychiatric Rating Scale (BPRS), and Barnes Akathisia Rating Scale (BARS) were used to evaluate insomnia, global psychiatric symptoms, and akathisia, respectively, in schizophrenic patients. RESULTS: Of the 182 schizophrenic patients, 39 (21.4%) were found to have RLS and 87 (47.8%) met at least one of the RLS diagnostic criteria. The prevalence of RLS was significantly higher in the schizophrenia group than in the control group (p=0.009), as were the RLS scores (p<0.001). The BPRS (p=0.001) and the AIS (p<0.001) scores were higher in the RLS group than in the group with no RLS symptoms. CONCLUSION: We conclude that it is important to consider the diagnosis of RLS when schizophrenic patients complain of insomnia, and that RLS symptoms could be associated with more severe psychiatric symptoms and insomnia.     

Leydig cell tumor in an elderly patient with complete androgen insensitivity syndrome

BACKGROUND: Androgen insensitivity syndrome (AIS) is usually diagnosed in phenotypically female patients at puberty with primary amenorrhea. Testicular tumors often develop in patients with AIS, Sertoli cell tumor and seminoma being the most common types. Leydig cell tumor in AIS is extremely rare. CASE: A large abdominal tumor developed in a 73-year-old female patient. Physical examination and cytogenetic analysis revealed that the patient was with complete AIS. The patient underwent the extirpation of bilateral gonads including the tumor, pelvic lymph nodes, omentum and appendix vermiformis. The pathological diagnosis was malignant Leydig cell tumor of the left testis. There was no invasion or dissemination grossly and histologically. There was no adjuvant radiation or chemotherapy performed. The post-operative course was uneventful. The patient showed no evidence of disease at the post-operative 1 month checkup. CONCLUSION: We reported an extremely rare case of malignant Leydig cell tumor developing in an elderly AIS patient.     

Genetic epidemiology and heritability of AIS: A study of 415 Chinese female patients

Recent familial segregation studies supported a multifactorial genetic model for the etiology of adolescent idiopathic scoliosis (AIS). However, the extent of quantitative genetic effects, such as heritability, have not been fully evaluated. This genetic epidemiology study examined the sibling recurrent risk and heritability of AIS in first‐degree relatives of 415 Chinese female patients, which is up to now the largest cohort. They were first diagnosed by community screening program and compared to 203 age‐matched normal controls. Out of the total 531 sibs of AIS cases, 94 sibs had scoliosis (sibling recurrence risk = 17.7%). The prevalence of AIS among male and female sibs of an index case were 11.5% (95% CI = 7.5–15.5) and 23.0% (95% CI = 18.1–27.9), respectively. Female sibs of an index case had an increased risk of 8.9‐fold (95% CI = 3.2–34.4) for developing AIS. These recurrent risks were significantly higher than the risk in the control group (p < 0.0001). Overall, heritability was estimated to be 87.5 ± 11.1%. The results confirmed the prevailing impression of strong genetic influence on the risk of AIS. Here we provided a large‐scale study for the genetic aggregation estimates in an Asian population for the first time. The finding also positioned AIS among other common disease or complex traits with a high heritability. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1464–1469, 2012     

Value of Barthel,PLAN and NIHSS scores for predicting the death of patients with acute ischemic stroke during their 5-year follow-up

ObjectiveThis study aimed to investigate the value of Barthel, PLAN, and NIHSS scores for predicting death in the 5-year follow-up after patients with AIS are discharged and find a simple and convenient predictive scale.MethodsData were prospectively collected from 678 patients with AIS. Patients’ death after 5 years of follow-up was considered the final event. The predictors of death were examined through single-factor and multivariate analysis. The receiver operating characteristic curve (ROC) of the patients’ Barthel, PLAN, and NIHSS scores was drawn, and the area under the curve (AUC) was calculated. Differences in the predictive power of the three scales were compared using MedCalc. The goodness of fit between predictive and actual models was evaluated with the Hosmer–Lemeshow method.ResultsMultivariate analysis suggested that the BI score was an independent predictor of death from AIS in the 5-year follow-up. The Barthel, PLAN, and NIHSS scale scores predicted the 5-year mortality AUC values of AIS were 0.687 [95% CI, (0.649–0.722)], 0.621 [95% CI, (0.583–0.659)], 0.637 [95% CI, (0.599–0.674)], the Hosmer–Lemeshow test revealed P > 0.05, indicating that the three models had a good fit. In pairwise comparison, the AUC value of the BI score was significantly greater than that of the NIHSS scores (Pc = 0.0189). BI and PLAN scores were very close to statistical significance (Pc = 0.0513). However, PLAN and NIHSS scores had no significant differences (Pc = 1.7493).ConclusionSimple BI scores had a high predictive value for the death of Chinese patients with AIS within 5 years.     

Activity-Based Therapy for Recovery of Walking in Chronic Spinal Cord Injury: Results From a Secondary Analysis to Determine Responsiveness to Therapy

ObjectiveTo gain insight into who is likely to benefit from activity-based therapy (ABT), as assessed by secondary analysis of data obtained from a clinical trial.DesignSecondary analysis of results from a randomized controlled trial with delayed treatment design.SettingOutpatient program in a private, nonprofit rehabilitation hospital.ParticipantsVolunteer sample of adults (N=38; 27 men; 11 women; age, 22–63y) with chronic (≥12mo postinjury), motor-incomplete (American Spinal Injury Association [ASIA] Impairment Scale [AIS] grade C or D) spinal cord injury (SCI).InterventionsA total of 9h/wk of ABT for 24 weeks including developmental sequencing; resistance training; repetitive, patterned motor activity; and task-specific locomotor training. Algorithms were used to guide group allocation, functional electrical stimulation utilization, and locomotor training progression.Main Outcome MeasuresWalking speed and endurance (10-meter walk test and 6-minute walk test) and functional ambulation (timed Up and Go test).ResultsThis secondary analysis identified likely responders to ABT on the basis of injury characteristics: AIS classification, time since injury, and initial walking ability. Training effects were the most clinically significant in AIS grade D participants with injuries <3 years in duration. This information, along with information about preliminary responsiveness to therapy (gains after 12wk), can help predict the degree of recovery likely from participation in an ABT program.ConclusionsABT has the potential to promote neurologic recovery and enhance walking ability in individuals with chronic, motor-incomplete SCI. However, not everyone with goals of walking recovery will benefit. Individuals with SCI should be advised of the time, effort, and resources required to undertake ABT. Practitioners are encouraged to use the findings from this trial to assist prospective participants in establishing realistic expectations for recovery.