Search

Cardiomyopathy, as well as hereditary muscular dystrophy, may be related to a deficiency of the glycoprotein called adhalin, which is part of the structure that links muscle cells together. Cardiomyopathy is disease of the heart muscle and adhalin is associated with the protein dystrophin, some forms of which are deficient in muscular dystrophy. A 13-year-old boy with muscular dystrophy had muscle weakness, an enlarged heart, arrythmia, and congestive heart failure received a heart transplant. Biopsies of his thigh and heart muscles showed that the muscle cell membranes were broken down. The levels of adhalin and a related structural glycoprotein were extremely low in the thigh muscle and undetectable in the heart muscle. Various causes, including mutation of the adhalin gene, may cause adhalin deficiency.

Abstract Background The amyloid β-peptide is a ubiquitous peptide, which is prone to aggregate forming soluble toxic oligomers and insoluble less-toxic aggregates. The intrinsic and external/environmental factors that determine Aβ aggregation in vivo are poorly understood, as well as the cellular meaning of this process itself. Genetic data as well as cell biological and biochemical evidence strongly support the hypothesis that Aβ is a major player in the onset and development of Alzheimer's disease. In addition, it is also known that Aβ is involved in Inclusion Body Myositis, a common myopathy of the elderly in which the peptide accumulates intracellularly. Results In the present work, we found that intracellular Aβ aggregation in muscle cells of Caenorhabditis elegans overexpressing Aβ peptide is affected by two single amino acid substitutions, E22G (Arctic) and V18A (NIC). Both variations show decrease intracellular amyloidogenesis compared to wild type Aβ. We show that intracellular amyloid aggregation of wild type Aβ is accelerated by Cu2+ and diminished by copper chelators. Moreover, we demonstrate through toxicity and behavioral assays that Aβ-transgenic worms display a higher tolerance to Cu2+ toxic effects and that this resistance may be linked to the formation of amyloid aggregates. Conclusion Our data show that intracellular Aβ amyloid aggregates may trap excess of free Cu2+ buffering its cytotoxic effects and that accelerated intracellular Aβ aggregation may be part of a cell protective mechanism.

Background: The International Classification of Headache Disorders lists different subtypes of medication overuse headache (MOH), according to the medication overused. The aim of this study is to evaluate whether the different subtypes correspond to clinically distinguishable phenotypes in a large population. Method: This descriptive cross‐sectional observational study included 660 patients with MOH referred to headache centers in Europe and Latin America as a part of the COMOESTAS project. Information about clinical features was collected with structured patient interviews and with self‐administered questionnaires for measuring disability, anxiety, and depression. Results: Female/male ratio, body mass index, marital status, and level of education were similar among in subjects enrolled in the 5 centers. The mean age was higher among subjects overusing triptans (T‐MOH) with respect to subjects overusing simple analgesic (A‐MOH). Duration of headache before chronification was longer in T‐MOH (19.2 ± 11.9 years) and in subjects overusing ergotamines (E‐MOH, 17.8 ± 11.7 years) with respect to the A‐MOH group (13.1 ± 10.9; P < .001 and P = .017, respectively) and in T‐MOH with respect multiple drug classes (M‐MOH, 14.9 ± 11.7; P = .030). Migraine Disability Assessment (MIDAS) score was significantly lower in E‐MOH group (33.6 ± 41.6), while T‐MOH group (56.8 ± 40.6) had a significant lower MIDAS score with respect to M‐MOH (67.2 ± 62.5; P = .016 and P = .037, respectively). Prevalence of depression and anxiety was lower in patients overusing T with respect to other groups of patients (χ2  = 10.953, P = .027 and χ2 = 25.725, P < .001, respectively). Conclusion: In this study on a large and very well characterized population of MOH, we describe the distinctive clinical characteristics of MOH subtypes. These findings contribute to more clearly define the clinical picture of a poorly delineated headache disorder. They also provide some insights in the possible trajectories leading to this highly disabling chronic headache, that is classified as a secondary form, but whose occurrence is entirely dependent on an underlying primary headache. [ABSTRACT FROM AUTHOR]

Background: Medication-overuse headache is a costly disease for individuals and society.Objective: To estimate the impact of medication-overuse headache treatment on direct and indirect headache-related health care costs.Methods: This prospective longitudinal study was part of the COMOESTAS project (COntinuous MOnitoring of Medication Overuse Headache in Europe and Latin America: development and STAndardization of an Alert and decision support System). Patients with medication-overuse headache were included from four European and two Latin American headache centers. Costs of acute medication, costs of health care services, and measurements of productivity were calculated at baseline and at 6-month follow-up Treatment consisted of overused drug withdrawal with optional preventive medication.Results: A total of 475 patients (71%) completed treatment and were followed up for 6 months. Direct health care costs were on average reduced significantly by 52% ( p < 0.001) for the total study population. Significant reductions were seen in both number of consumed tablets (-71%, p < 0.001) and number of visits to physicians (-43%, p < 0.001). Fifty percent of patients reduced their number of consumed tablets ≥ 80%. Headache-related productivity loss, calculated either as absence from work or ≥ 50% reduction of productivity during the workday, were reduced by 21% and 34%, respectively ( p < 0.001).Conclusion: Standardized treatment of medication-overuse headache in six countries significantly reduced direct health care costs and increased productivity. This emphasizes the importance of increasing awareness of the value of treating medication-overuse headache.Trial Registration: The trial was registered at ClinicalTrials.gov (no. NCT02435056). [ABSTRACT FROM AUTHOR]

Aim: To identify factors that may be predictors of the outcome of a detoxification treatment in medication-overuse headache.Methods: Consecutive patients entering a detoxification program in six centres in Europe and Latin America were evaluated and followed up for 6 months. We evaluated anxious and depressive symptomatology (though patients with severe psychiatric comorbidity were excluded), quality of life, headache-related disability, headache characteristics, and prophylaxis upon discharge.Results: Of the 492 patients who completed the six-month follow up, 407 ceased overuse following the detoxification (non overusers), another 23 ceased overuse following detoxification but relapsed during the follow-up. In the 407 non-overusers, headache acquired an episodic pattern in 287 subjects (responders). At the multivariate analyses, lower depression scores (odds ratio = 0.891; p = 0.001) predicted ceasing overuse. The primary headache diagnosis - migraine with respect to tension-type headache (odds ratio = 0.224; p = 0.001) or migraine plus tension-type headache (odds ratio = 0.467; p = 0.002) - and the preventive treatment with flunarizine (compared to no such treatment) (odds ratio = 0.891; p = 0.001) predicted being a responder. A longer duration of chronic headache (odds ratio = 1.053; p = 0.032) predicted relapse into overuse. Quality of life and disability were not associated with any of the outcomes.Conclusions: Though exploratory in nature, these findings point to specific factors that are associated with a positive outcome of medication-overuse headache management, while identifying others that may be associated with a negative outcome. Evaluation of the presence/absence of these factors may help to optimize the management of this challenging groups of chronic headache sufferers. [ABSTRACT FROM AUTHOR]

Aims To evaluate the impact of treatment success on depression and anxiety symptoms in medication-overuse headache (MOH) and whether depression and anxiety can be predictors of treatment outcome. Methods All consecutive patients entering the detoxification program were analysed in a prospective, non-randomised fashion over a six-month period. Depression and anxiety were assessed using the Hospital Anxiety and Depression Scale. Results A total of 663 MOH patients were evaluated, and 492 completed the entire protocol. Of these, 287 ceased overuse and reverted to an episodic pattern (responders) and 23 relapsed into overuse. At the final evaluation, the number of patients with depressive symptoms was reduced by 63.2% among responders ( p < 0.001) and did not change in relapsers ( p = 0.13). Anxious symptomatology was reduced by 43.1% in responders ( ps < 0.001) and did not change in relapsers ( p = 0.69). At the multivariate analysis, intake of a prophylactic drug and absence of symptoms of depression at six months emerged as prognostic factors for being a responder (OR 2.406; p = 0.002 and OR 1.989; p = 0.019 respectively), while lack of antidepressant drugs and presence of symptoms of depression at six months were prognostic factors for relapse into overuse (OR 3.745; p = 0.004 and OR 3.439; p = 0.031 respectively). Conclusions Symptomatology referred to affective state and anxiety can be significantly reduced by the treatment of MOH. Baseline levels of depression and anxiety do not generally predict the outcome at six months. Their persistence may represent a trait of patients with a negative outcome, rather than the consequence of a treatment failure. [ABSTRACT FROM AUTHOR]

Background Medication-overuse headache (MOH) is a chronic disabling condition associated with a high rate of relapse. Methods We evaluated whether the adoption of electronic-assisted monitoring, advice and communication would improve the outcome over a follow-up of 6 months in a controlled, multicentre, multinational study conducted in six headache centres located in Europe and Latin America. A total of 663 MOH subjects were enrolled and divided into two groups: the Comoestas group was monitored with an electronic diary associated with an alert system and a facilitated communication option, and the Classic group with a paper headache diary. Results We observed a significantly higher percentage of overuse-free subjects in the Comoestas group compared with the Classic group: 73.1 vs 64.1% (odds ratio 1.45, 95% confidence interval 1.07-2.09, p = 0.046). The Comoestas group performed better also regarding the number of days/month with intake of acute drugs and the level of disability [Migraine Disability Assessment Score: Comoestas group - 42.5 ± 53.6 (35.5-49.3) and Classic group - 27.5 ± 56.1 (20.6-34.3) ( p < 0.003)]. Conclusion The adoption of the electronic tool improved the outcome of patients suffering from MOH after withdrawal from overused drugs. Information and communication technology represents a valid aid for optimizing the management of chronic conditions at risk of worsening or of relapsing. Trial registration The trial was registered at ClinicalTrials.gov (no. NCT02435056). [ABSTRACT FROM AUTHOR]

Background: Medication overuse headache (MOH) is a very disabling and costly disorder due to indirect costs, medication and healthcare utilization. The aim of the study was to describe general demographic and clinical characteristics of MOH, along with the national referral pathways and national painkillers distribution in several European and Latin American (LA) Countries., Methods: This descriptive cross-sectional observational study included 669 patients with MOH referred to headache-centers in Europe and LA as a part of the COMOESTAS project. Information about acute medication and healthcare utilization were collected by extensive questionnaires, supplemented with structured patient interviews., Results: Triptans were overused by 31 % European patients and by 6 % in LA (p < 0.001), whereas ergotamines were overused by 4 % in Europe and 72 % in LA (p < 0.001). Simple analgesics were overused by 54 % in Europe and by 33 % in LA (p < 0.001), while combination-analgesics were more equally overused (24 % in Europe and 29 % in LA). More European patients (57 %) compared with LA patients (27 %) visited general practitioners (p < 0.001), and 83 % of European patients compared to 38 % in LA consulted headache specialists (p < 0.001). A total of 20 % in Europe and 30 % in LA visited emergency rooms (p = 0.007)., Conclusion: There are marked variations between LA and Europe in healthcare pathways and in acute medication overuse regarding patients with MOH. This should be considered when planning prevention campaigns against MOH.