A set of related medical disorders that lack a proper classification system and diagnostic criteria is like a society without laws. The result is incoherence at best, chaos at worst. For this reason, the International Classification of Headache Disorders (ICHD) is arguably the single most important breakthrough in headache medicine over the last 50 years. The ICHD identifies and categorizes more than a hundred different kinds of headache in a logical, hierarchal system. Even more important, it has provided explicit diagnostic criteria for all of the headache disorders listed. The ICHD quickly became universally accepted, and criticism of the classification has been minor relative to that directed at other disease classification systems. Over the 20 years following publication of the first edition of the ICHD, headache research has rapidly accelerated despite sparse allocation of resources to that effort. In summary, the ICHD has attained widespread acceptance at the international level and has substantially facilitated both clinical research and clinical care in the field of headache medicine.

International Classification of Headache Disorders

To review the pathophysiologic, epidemiologic, and clinical evidence for similarities and differences between migraine with and without aura. The ICHD-3 has recently refined the diagnostic criteria for aura to include positive symptomatology, which better differentiates aura from TIA. Although substantial evidence supports cortical spreading depression as the cause of visual aura, the role (if any) of CSD in headache pain is not well understood. Recent imaging evidence suggests a possible hypothalamic origin for a headache attack, but further research is needed. Migraine with aura is associated with a modest increase in the risk of ischemic stroke. The etiology for this association remains unclear. There is a paucity of evidence regarding treatments specifically aimed at the migraine with aura subtype, or whether migraine with vs without aura responds to treatment differently. Migraine with typical aura is therefore often treated similarly to migraine without aura. Lamotrigine, daily aspirin, and flunarizine have evidence for efficacy in prevention of migraine with aura, and magnesium, ketamine, furosemide, and single-pulse transcranial magnetic stimulation have evidence for use as acute treatments. Although triptans have traditionally been contraindicated in hemiplegic migraine and migraine with brainstem aura, this prohibition is being reconsidered in the face of evidence suggesting that use may be safe. The debate as to whether migraine with and without aura are different entities is ongoing. In an era of sophisticated imaging, genetic advancement, and ongoing clinical trials, efforts to answer this question are likely to yield important and clinically meaningful results.

Episodic Migraine With and Without Aura: Key Differences and Implications for Pathophysiology, Management, and Assessing Risks.

Atrial fibrillation (AF) is a highly prevalent arrhythmia that causes high morbidity and mortality. However, the underlying mechanism of AF has not been fully elucidated. Recent research has suggested that, during AF, the immune system changes considerably and interacts with the environment and cells involved in the initiation and maintenance of AF. This may provide a new direction for research and therapeutic strategies for AF. In this review, we elaborate the concept of immune remodeling based on available data in AF. Then, we highlight the complex relationships between immune remodeling and atrial electrical, structural and neural remodeling while also pointing out some research gaps in these field. Finally, we discuss several potential immunomodulatory treatments for AF. Although the heterogeneity of existing evidence makes it ambiguous to extrapolate immunomodulatory treatments for AF into the clinical practice, immune remodeling is still an evolving concept in AF pathophysiology and further studies within this field are likely to provide effective therapies for AF. 

/pdf/immune-remodeling-and-atrial-fibrillation-2qjwv7am.pdf

Immune remodeling and atrial fibrillation

Atrial fibrillation (AF) is an increasingly prevalent arrhythmia with significant health and socioeconomic impact. The underlying mechanism of AF is still not well understood. In this study, we sought to identify hub genes involved in AF, and explored their functions and underlying mechanisms based on bioinformatics analysis. Five microarray datasets in GEO were used to identify the differentially expressed genes (DEGs) by Robust Rank Aggregation (RRA), and hub genes were screened out using protein–protein interaction (PPI) network. AF model was established using a mixture of acetylcholine and calcium chloride (Ach-CaCl2) by tail vein injection. We totally got 35 robust DEGs that mainly involve in extracellular matrix formation, leukocyte transendothelial migration, and chemokine signaling pathway. Among these DEGs, we identified three hub genes involved in AF, of which CXCL12/CXCR4 axis significantly upregulated in AF patients stands out as one of the most potent targets for AF prevention, and its effect on AF pathogenesis and underlying mechanisms were investigated in vivo subsequently with the specific CXCR4 antagonist AMD3100 (6 mg/kg). Our results demonstrated an elevated transcription and translation of CXCL12/CXCR4 axis in AF patients and mice, accompanied with the anabatic atrial inflammation and fibrosis, thereby providing the substrate for AF maintenance. Blocking its signaling via AMD3100 administration in AF model mice reduced AF inducibility and duration, partly ascribed to decreased atrial inflammation and structural remodeling. Mechanistically, these effects were achieved by reducing the recruitment of CD3+ T lymphocytes and F4/80+ macrophages, and suppressing the hyperactivation of ERK1/2 and AKT/mTOR signaling in atria of AF model mice. In conclusion, this study provides new evidence that antagonizing CXCR4 prevents the development of AF, and suggests that CXCL12/CXCR4 axis may be a potential therapeutic target for AF.

/pdf/cxcl12-cxcr4-axis-as-a-key-mediator-in-atrial-fibrillation-1biyej6seq.pdf

CXCL12/CXCR4 axis as a key mediator in atrial fibrillation via bioinformatics analysis and functional identification.

The purpose of this study was to test the feasibility and usefulness of the International Classification of Headache Disorders, third edition, beta version (ICHD-3β), and compare the differences with the International Classification of Headache Disorders, second edition (ICHD-2). Consecutive first-visit patients were recruited from 11 headache clinics in Korea. Headache classification was performed in accordance with ICHD-3β. The characteristics of headaches were analyzed and the feasibility and usefulness of this version was assessed by the proportion of unclassified headache disorders compared with ICHD-2. A total of 1,627 patients were enrolled (mean age, 47.4±14.7 yr; 62.8% female). Classification by ICHD-3β was achieved in 97.8% of headache patients, whereas 90.0% could be classified by ICHD-2. Primary headaches (n=1,429, 87.8%) were classified as follows: 697 migraines, 445 tension-type headaches, 22 cluster headaches, and 265 other primary headache disorders. Secondary headache or painful cranial neuropathies/other facial pains were diagnosed in 163 patients (10.0%). Only 2.2% were not classified by ICHD-3β. The main reasons for missing classifications were insufficient information (1.6%) or absence of suitable classification (0.6%). The diagnoses differed from those using ICHD-2 in 243 patients (14.9%). Among them, 165 patients were newly classified from unclassified with ICHD-2 because of the relaxation of the previous strict criteria or the introduction of a new diagnostic category. ICHD-3β would yield a higher classification rate than its previous version, ICHD-2. ICHD-3β is applicable in clinical practice for first-visit headache patients of a referral hospital.

/pdf/comprehensive-application-of-the-international-2u11tk9gam.pdf

Comprehensive Application of the International Classification of Headache Disorders Third Edition, Beta Version

Objectives: Stromal cell-derived factor 1a (SDF-1α), is a chemokine and is able to home hematopoietic progenitor cells to injured areas of heart tissue for structural repair. Previous studies have found increased levels of SDF-1α in several cardiac diseases, but only few studies have investigated SDF-1α in patients with atrial fibrillation (AF). We aimed to test SDF-1α in a large cohort of patients with AF and its role as a prognostic marker. Design: Between January 1st 2008 to December 1st 2012, 290 patients with ECG documented AF were enrolled from the in- and outpatient clinics at the Department of Cardiology, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark. Plasma levels of SDF-1α were measured using ELISA technique. Clinical data were registered and patient follow-up was conducted. Results: Patients with permanent AF had significantly higher SDF-1α levels (2199.5 pg/ml) than the patients with paroxysmal AF (1982.0 pg/ml) and persistent AF (1906.0 pg/ml), p < 0.0005. Higher SDF-...

Stromal cell-derived factor 1α (SDF-1α): A marker of disease burden in patients with atrial fibrillation.

The Forgotten Joint Score (FJS) is a novel measurement for patients’ awareness of their knee in daily life. By identifying factors that could explain pre-operative FJS levels, the clinician could better prioritize and single out patients who would benefit most from TKA. The aim of this study was to identify possible factors that may explain the variance of pre-operative FJS levels and evaluate the relationship between pre-operative FJS and pre-operative Oxford Knee Score (OKS). Four-hundred and six individual knees undergoing primary TKA between 2014 and 2016 were included in the study. Age, gender, body mass index (BMI), pre-operative FJS and pre-operative OKS were obtained maximum 2 weeks prior to surgery. Kellgren–Lawrence (K–L) grade, alignment and joint space width (JSW) were evaluated on pre-operative radiographs. Mean FJS was 21.1 ± 15.6. Females, younger patients and patients with high BMI had significantly the worst pre-operative FJS (p < 0.005). Females scored 6.5 FJS points lower than males. A 0.2-point increase in FJS for every added year indicated improvement in knee awareness with age. A 0.4-point decrease in FJS points for every added BMI point indicated worse knee awareness with higher BMI. There was a strong positive correlation between pre-operative FJS and pre-operative OKS according to the Spearman’s rank order test (p < 0.005). Females, younger patients and patients with high BMI had significantly the worst pre-operative joint awareness. FJS had a strong positive correlation to OKS in pre-operative patients for primary TKA. This information can be used for improved patient selection; clinically continuous low FJS despite weight loss and/or the passing of time may be indication for TKA. Prospective cohort study, Level II.

Females, younger patients and patients with high BMI have the highest pre-operative knee awareness measured using the Forgotten Joint Score.

IntroductionIn 2013 the International Headache Society published the third International Classification of Headache Disorders beta-version, ICHD-3 beta. Its structure is identical to that of the pr...

Field-testing of the ICHD-3 beta/proposed ICD-11 diagnostic criteria for migraine with aura.

Background 
In patients with paroxysmal atrial fibrillation (PAF) or persistent atrial fibrillation (PeAF) symptom burden and fear of hospital readmission are major causes of reduced quality of life. We attempted to develop a prediction model for future atrial fibrillation hospitalization (AFH) risk in PAF and PeAF patients including all previously experienced AFHs in the analysis, as opposed to time to first event.


Methods 
Recurrent event survival analysis was used to model the impact of past AFHs on the risk of future AFHs. A recurrent event was defined as a hospitalization due to a new episode of AF. Death or progression to permanent AF were included as competing risks.


Results 
We enrolled 174 patients with PAF or PeAF, mean follow up duration was 1279 days, and 325 AFHs were observed. Median patient age was 63.0 (IQR 52.2–68.0), 29% had PAF, and 71% were male. Highly significant predictors of future AFH risk were PeAF (HR 3.20, CI 2.01–5.11) and number of past AFHs observed (HR for 1 event: 2.97, CI 2.04–4.32, HR for ≥2 events: 7.54, CI 5.47–10.40).


Conclusion 
In PAF and PeAF patients, AF type and observed AFH frequency are highly significant predictors of future AFH risk. The developed model enables risk prediction in individual patients based on AFH history and baseline characteristics, utilizing all events experienced by the patient. This is the first time recurrent event survival analysis has been used in AF patients.

/pdf/recurrent-event-survival-analysis-predicts-future-risk-of-1j23dbvb71.pdf

Recurrent event survival analysis predicts future risk of hospitalization in patients with paroxysmal and persistent atrial fibrillation

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Stromal cell-derived factor 1α (SDF-1α): A marker of disease burden in patients with atrial fibrillation.

Females, younger patients and patients with high BMI have the highest pre-operative knee awareness measured using the Forgotten Joint Score.

Field-testing of the ICHD-3 beta/proposed ICD-11 diagnostic criteria for migraine with aura.

Recurrent event survival analysis predicts future risk of hospitalization in patients with paroxysmal and persistent atrial fibrillation