Expression of stromal‐cell‐derived factor‐1 (SDF‐1): a predictor of ischaemic stroke?

Background and purpose: Platelet stromal‐cell‐derived factor‐1 (SDF‐1) plays a pivotal role in angiogenesis and the regeneration of ischaemic tissue through the regulation of haematopoietic progenitor cells and is upregulated at the sites of vascular injury and platelet activation. Thus, SDF‐1 has recently been discussed as a predictor in ischaemic diseases such as acute myocardial infarction. However, no clinical data pertinent to the investigation of the platelet SDF‐1 expression in patients with stroke are available. Methods: We consecutively evaluated 196 patients who were admitted to the stroke unit with symptoms suspected for stroke. Surface expression of the platelet activation markers (P‐selectin and GPIb) and the expression of platelet‐bound SDF‐1 were determined by two‐colour whole blood flow cytometry. Results: Patients with transient ischaemic attack (TIA) as well as with ischaemic stroke showed similar levels of SDF‐1 expression on hospital admission compared with patients with non‐ischaemic (NI) events and with 30 healthy controls (TIA (mean fluorescence intensity ± SD): 31.5 ± 18.2 vs. NI: 26.4 ± 15.7; P = 0.361; stroke: 28.7 ± 19.8 vs. NI; P = 0.943; control: 26.1 ± 11.3; P > 0.05 compared with all). Platelet SDF‐1 expression showed a trend with the severity of stroke according to National Institute of Health Stroke Scale score (r = 0.125; P = 0.085), but significantly correlated with the peak levels of C‐reactive protein (r = 0.218; P = 0.002) and with the levels of platelet activation (P‐selectin: r = 0.389; P = 0.001). Multifactorial analysis of covariance revealed a significant influence on platelet SDF‐1 expression by smoking (P = 0.019). Conclusions: Platelet SDF‐1 surface expression did not show any significant difference in patients with TIA and ischaemic stroke compared with patients with NI events. Thus, single biomarker evaluation of platelet SDF‐1 surface expression is not helpful to predict ischaemic stroke.     

Can ACTH therapy improve the long‐term outcome of drug‐resistant frontal lobe epilepsy?

Frontal lobe epilepsy is a common focal epilepsy in children and is often difficult to treat. Adrenocorticotropic hormone (ACTH) or steroids have been used for patients with several forms of medically intractable epilepsy. We evaluated the short, medium, and long‐term evolution of patients with frontal lobe epilepsy and secondary bilateral synchrony on the EEG, who received ACTH treatment. Patients were recruited for an add‐on trial during clinical practice, and data was retrospectively analysed. The study group comprised 6 patients treated with ACTH. The effects of ACTH were assessed in the short term (at the end of a 6‐week period of ACTH treatment), medium term (at 6 months after the end of treatment), and long term (at 12 months after the end of treatment). At short‐term follow‐up, ACTH treatment was effective for all types of seizures in 5 of 6 patients and ineffective in 1 patient. All patients who were seizure‐free at the end of ACTH treatment maintained an excellent outcome, remaining seizure‐free at the end of follow‐up. Our study demonstrates that ACTH may represent an effective treatment for frontal lobe epilepsy with secondary bilateral synchrony. Further double‐blind prospective studies are required to confirm our initial findings.     

Is the presence of urinary indolyl‐3‐acryloylglycine associated with autism spectrum disorder?

To test whether the presence of indolyl-3-acryloylglycine (IAG) is associated with autism, we analyzed urine from population-based, blinded cohorts. All children in York, UK with autism spectrum disorders (ASDs), diagnosed using ICD-10 research diagnostic criteria, were invited to participate. Fifty-six children on the autism spectrum (mean age 9y 8mo, SD 3y 8mo; 79% male) agreed to participate, as did 155 children without ASDs (mean age 10y, SD 3y 2mo; 54% male) in mainstream and special schools (56 of whom were age-, sex-, and school-matched to children with ASDs). IAG was found at similar levels in the urine of all children, whether IAG concentrations or IAG:creatinine ratios were compared. There was no significant difference between the ASD and the comparison group, and no difference between children at mainstream schools and those at special schools. There is no association between presence of IAG in urine and autism; therefore, it is unlikely to be of help either diagnostically or as a basis for recommending therapeutic intervention with dietary manipulation. The significance of the presence of IAG in urine has yet to be determined.     

Does the Cause of Localisation‐Related Epilepsy Influence the Response to Antiepileptic Drug Treatment?

PURPOSE: We investigated the response to antiepileptic drug (AED) therapy in patients with localisation-related epilepsy associated with different underlying causes. METHODS: Five hundred and fifty adolescent and adult patients who had partial epilepsy treated with AEDs and who had undergone magnetic resonance imaging of brain were followed up prospectively from 1984 at a single centre. More than 70% were newly diagnosed. None had had epilepsy surgery. RESULTS: Three hundred and twelve (57%) patients had been seizure free at their last clinic visit for at least a year. Patients with mesial temporal sclerosis (MTS; n = 73, 42% seizure free) were less likely to be controlled (p < 0.01) than were those with arteriovenous malformation (AVM; n = 14, 78%), cerebral infarction (n = 46, 67%), primary tumour (n = 35, 63%), cortical gliosis (n = 81, 57%), cerebral atrophy (n = 49, 55%), and cortical dysplasia (CD; n = 63, 54%). Among the seizure-free patients, those with MTS were more likely to require more than one AED compared with those with other aetiologies (48 vs. 35%; p < 0.05). There was no difference in outcome between patients with symptomatic and cryptogenic epilepsy (n = 361, 58% vs. n = 189, 56% seizure free, respectively). Patients with MTS, CD, and cryptogenic epilepsy were more likely (p = 0.02) to have a family history of epilepsy than were the other groups. MTS patients also had a higher incidence of febrile convulsions (p < 0.001). CONCLUSIONS: The majority of patients with focal-onset epilepsy became seizure free on AED treatment. MTS-related seizures had the worst prognosis. Although many patients with this pathology may benefit from epilepsy surgery, a considerable number will be controlled with AED therapy.     

Abstinence from cocaine‐self‐administration activates the nELAV/GAP ‐43 pathway in the hippocampus: A stress‐related effect?

We previously demonstrated that nELAV/GAP‐43 pathway is pivotal for learning and its hippocampal expression is up‐regulated by acute stress following repeated cocaine administration. We therefore hypothesized that abstinence‐induced stress may sustain nELAV/GAP‐43 pathway during early abstinence following 2 weeks of cocaine self‐administration. We found that contingent, but not non‐contingent, cocaine exposure selectively increases hippocampal nELAV, but not GAP‐43, expression immediately after the last self‐administration session, an effect that wanes after 24 h and that comes back 7 days later when nELAV activation becomes associated with increased expression of GAP‐43, an effect again observed only in animals self‐administering the psychostimulant. Such effect is specific for nELAV since the ubiquitous ELAV/HuR is unchanged. This nELAV profile suggests that its initial transient alteration is perhaps related to the daily administration of cocaine, while the increase in the nELAV/GAP‐43 pathway following a week of abstinence may reflect the activation of this cascade as a target of stressful conditions associated with drug‐related memories. © 2016 Wiley Periodicals, Inc.     

The response scale for the intellectual disability module of the WHOQOL: 5‐point or 3‐point?

Objective To deal with the question of whether a 5‐point response Likert scale should be changed to a 3‐point scale when used in the field testing of people with intellectual disabilities (IDs), which was raised after the pilot study of World Health Organization Quality of Life (WHOQOL)‐DIS, a module being developed with the World Health Organization measure of quality of life for disabilities. Methods Three possible ways were used to generate hypothetical data by merging a 5‐point scale into a 3‐point scale. The analyses were based on both item response theory and classical measurement theory. The partial credit model for polytomous response was performed for item evaluation; the confirmatory factor analysis was used to check construct validity, the Cronbach's alpha for domain reliability, and correlation analyses for the relationship between the 5‐point scale and the generated 3‐point scale. Results Most items with a 5‐point response scale had disordered response options and/or unequal‐length intervals between successive response options; these deficiencies were removed or improved without decline of validity and reliability in the hypothetical data of 3‐point scales. Conclusion Instead of the 5‐point scale, a 3‐point scale could be used for IDs in the field test of developing the module WHOQOL‐DIS.     

Self‐reported utilization of mental health services in the adult German population – evidence for unmet needs? Results of the DEGS1‐Mental Health Module (DEGS1‐MH)

This paper provides up‐to‐date data on service use for mental health problems and disorders among adults aged 18‐79 years in Germany derived from the Mental Health Module of the German Health Interview and Examination Survey for Adults (DEGS1‐MH; N=4483). Data are based exclusively on self‐report. Respondents were examined by clinically trained interviewers with a modified version of the Composite International Diagnostic Interview DIA‐X/M‐CIDI to assess diagnoses according to the criteria of DSM‐IV‐TR. Service use, i.e. contact to mental health care services, due to mental health problems was assessed for the past 12 months and lifetime, by type of sector and type of institution. Among respondents with a 12‐month diagnosis of a mental disorder, 23.5% of the women and 11.6% of the men reported any service use in the past 12 months. Service use depends on type of diagnosis, comorbidity and socio‐demographic characteristics. Lowest 12‐month utilization rates were found for substance use disorders (15.6%; lifetime use 37.3%), highest for psychotic disorders (40.5%; lifetime 72.1%). Further, a considerable time lap was found between disorder onset and subsequent service use among the majority of cases with anxiety and mood disorders. This paper provides self‐reported epidemiological data on mental health service use in Germany, complementing administrative statistics and the predecessor mental health module of the German Health Interview and Examination Survey (GHS‐MHS) from 1998. Despite considerable changes in the mental health field in Germany and the existence of a comprehensive mental health care system without major financial barriers, we find no indications of substantially higher utilization rates for mental disorders as compared to other comparable European countries. Further, no indications of major overall changes in utilization rates are apparent. To pinpoint areas with unmet needs, more detailed analyses of the data are needed taking into account type, frequency, and adequacy of service use and treatment of mental disorders. Appropriately matched comparisons with the GHS‐MHS are needed to identify changes in patterns of utilization and interventions by type of disorder. Copyright © 2014 John Wiley & Sons, Ltd.     

Is the Val66Met polymorphism of the brain‐derived neurotrophic factor gene associated with panic disorder? A meta‐analysis

Although emerging evidence has suggested an association between the Val66Met (rs6265) polymorphisms in brain‐derived neurotrophic factor (BDNF) gene and the panic disorder, the conclusion is inclusive given the mixed results. This meta‐analysis reviewed and analyzed the recent studies addressing the potential association between the Val66Met polymorphisms and panic disorder susceptibility. Related case–control studies were retrieved by database searching and selected according to established inclusion criteria. Six articles were identified, which explored the association between the BDNF Val66Met polymorphism and panic disorder. Statistical analyses revealed no association for the allele contrast and the dominant model. However, the recessive model showed a significant association between the BDNF Val66Met polymorphism and panic disorder (odds ratio = 1.26, 95% confidence interval = 1.04–1.52, z = 2.39, P = 0.02). Despite of some limitations, this meta‐analysis suggests that the Val66Met polymorphism of BDNF gene is a susceptibility factor for panic disorder.     

Nav1.4 slow‐inactivation: Is it a player in the warm‐up phenomenon of myotonic disorders?

Myotonia is a heritable disorder in which patients are unable to willfully relax their muscles. The physiological basis for myotonia lies in well‐established deficiencies of skeletal muscle chloride and sodium conductances. What is unclear is how normal muscle function can temporarily return with repeated movement, the so‐called “warm‐up” phenomenon. Electrophysiological analyses of the skeletal muscle voltage‐gated sodium channel Na_v1.4 (gene name SCN4A), a key player in myotonia, have revealed several parallels between the Na_v1.4 biophysical signature, specifically slow‐inactivation, and myotonic warm‐up, which suggest that Na_v1.4 is critical not only in producing the myotonic reaction, but also in mediating the warm‐up. Muscle Nerve, 2013