Revision Of Diagnostic Criteria Research Articles

Impact of the 2022 ESC/ERS revised hemodynamic definition on the diagnosis of pulmonary hypertension

Objectives: In the 2022 European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines, the hemodynamic definition of pulmonary hypertension (PH) was revised to mean pulmonary arterial pressure (mPAP)>20 mmHg (1 mmHg=0.133 kPa) at rest. This study aimed to evaluate the impact of the revised hemodynamic definition on the diagnosis of PH. Methods: Patients with dyspnea or highly suspected PH who underwent right heart catheterization (RHC) in Beijing Anzhen hospital affiliated to Capital Medical University from September 2021 to October 2022 were enrolled retrospectively. According to resting hemodynamics, the patients were divided into 3 groups: no-PH (mPAP≤20 mmHg) group, low-pressure PH (20 mmHg<mPAP<25 mmHg) group and high-pressure PH (mPAP≥25 mmHg) group. The diagnosis and classification of PH and the hemodynamic parameters in different groups were compared before and after the revision of diagnostic criteria. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of maximum of mPAP (mPAPmax) and mPAP/cardiac output (CO) slope of multi-point in PH. Results: A total of 117 patients were included for analysis, the age was (53.7±17.5) years, 37 (31.6%) patients were male. According to the 2022 ESC/ERS definition, 99 patients were diagnosed as PH, including 8 patients (6.8%) in the low-pressure PH group and 91 patients (77.8%) in the high-pressure PH group. There were 18 patients (15.4%) in the non-PH group. Comparing to the 2015 ESC/ERS definition, 8 patients were newly diagnosed as PH. Echocardiography indexes pulmonary systolic pressure (sPAP) [(57.6±7.3) vs (38.5±13.6) mmHg], max tricuspid regurgitation velocity (TRVmax) [(360.4±28.9) vs (271.4±52.2) cm/s] and RHC index mPAP [(22.2±1.3) vs (16.1±2.6) mmHg] in low-pressure PH group were higher than those in no-PH group (all P<0.05). However, further analysis of hemodynamics during exercise showed mPAPmax [(42.1±5.6) vs (35.6±4.7) mmHg, P=0.006] and mPAP/CO slope of multi-point [(4.9±1.3) vs (3.6±1.1) mmHg·L-1·min-1,P=0.024] in low-pressure PH group were higher than those in no-PH group. The ROC curve cut-off value of mPAPmax for the diagnosis of PH was 39 mmHg, with a sensitivity of 75.0%, a specificity of 76.5%, and the area under the curve (AUC) and 95%CI is 0.816 (0.638-0.994). The ROC curve cut-off value of mPAP/CO slope of multi-point for the diagnosis of PH was 4.44 mmHg·L-1·min-1,with a sensitivity of 75.0%, a specificity of 76.5%, and an AUC (95%CI) of 0.794 (0.606-0.983). Conclusion: After the revision of the hemodynamic definition of PH in the 2022 ESC/ERS guidelines, more PH patients with pulmonary vascular disease are detected, thereby facilitating early diagnosis and treatment.

Unveiling the Structure in Mental Disorder Presentations

DSM criteria are polythetic, allowing for heterogeneity of symptoms among individuals with the same disorder. In empirical research, most combinations were not found or only rarely found, prompting criticism of this heterogeneity. To elaborate how symptom-based definitions and assessments contribute to a distinct probability pattern for the occurrence of symptom combinations. This cross-sectional study involved a theoretical argument, simulation, and secondary data analysis of 4 preexisting datasets, each consisting of symptoms from 1 of the following syndromes: posttraumatic stress disorder, depression, schizophrenia, and anxiety. Data were obtained from various sources, including the National Institute of Mental Health Data Archive and Department of Veteran Affairs. A total of 155 474 participants were included (individual studies were 3930 to 63 742 individuals in size). Data were analyzed between July 2021 and January 2024. For each participant, the presence or absence of each assessed symptom and their combination was determined. The number of all combinations and their individual frequencies were assessed. Probability or frequency of unique symptom combinations and their distribution. Among the 155 474 participants, the mean (SD) age was 47.5 (14.8) years; 33 933 (21.8%) self-identified as female and 121 541 (78.2%) as male. Because of the interrelation between symptoms, some symptom combinations were significantly more likely than others. The distribution of the combinations' probability was heavily skewed with most combinations having a very low probability. Across all 4 empirical samples, the 1% most common combinations were prevalent in a total of 33.1% to 78.6% of the corresponding sample. At the same time, many combinations (ranging from 41.7% to 99.8%) were reported by less than 1% of the sample. This study found that within-disorder symptom heterogeneity followed a specific pattern consisting of few prevalent, prototypical combinations and numerous combinations with a very low probability of occurrence. Future discussions about the revision of diagnostic criteria should take this specific pattern into account by focusing not only on the absolute number of symptom combinations but also on their individual and cumulative probabilities. Findings from clinical populations using common diagnostic criteria may have limited generalizability to the large group of individuals with a low-probability symptom combination.

What is new in the 5th edition of the World Health Organization classification of mature B and T/NK cell tumors and stromal neoplasms?

The classification of tumors is essential in the diagnosis and clinical management of patients with malignant neoplasms. The World Health Organization (WHO) provides a globally applicable classification scheme of neoplasms and it was updated several times. In this review, we briefly outline the cornerstones of the upcoming 5th edition of the World Health Organization Classification of Haematolymphoid Tumours on lymphoid neoplasms. As is adopted throughout the 5th edition of the WHO classification of tumors of all organ systems, entities are listed by a hierarchical system. For the first time, tumor-like lesions have been included in the classification, and modifications of nomenclature for some entities, revisions of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities are presented along with mesenchymal lesions specific to the stroma of lymph nodes and the spleen. In addition to specific outlines on constitutional and somatic genetic changes associated with given entities, a separate chapter on germline predisposition syndromes related to hematologic neoplasms has been added.

Approaches in Managing Resistant Hypertension: A Review.

In India, around 234 million adults (one in three) suffer from hypertension (HTN). An average of 10% of these cases are likely to be resistant hypertension (RH). This load of 23 million patients is expected to expand further with revisions in diagnostic criteria. The treatment and control rates of hypertension in India average around 30% and 15%, respectively. Pharmacological management involves a stepwise approach starting with optimizing the A-C-D (angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs), and thiazide-like diuretics) triple-drug combination, followed by substitution with a thiazide-like diuretic and use of spironolactone as a next step (fourthdrug). The subsequent steps are suggestions based on expert input and must be individualized. These include using a β-blocker as the fifth drug and an α1-blocker or a peripheral vasodilator as a final option when target blood pressure (BP) values are not achieved. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are likely to be helpful in managing RH due to their renal and cardiovascular protection as well as mortality benefits. SGLT2i lowers BP independent of the dosage and concomitant anti-hypertensive medications. Patient education and tools to monitor BP and treatment compliance will improve outcomes with these medications. In addition to therapeutic intervention, a preventive approach for RH mandates a need to identify patients at risk and use appropriate preventive and optimal therapy to prevent uncontrolled hypertension in patients with cardiovascular disorders.

ICD-11 Primary Psychotic Disorders: What is New and May be Relevant for Treatment Selection and Outcome?

ICD-11 was released by WHO in 2018 and approved by the World Health Assembly (WHA) in 2019. The revision for all chapters was guided by the principles of global applicability, scientific validity and clinical utility. The new chapter for mental health is termed 06 Mental, Behavioural or Neurodevelopmental Disorders (MBND). The ICD-11 with its chapter on Mental, Behavioural or Neurodevelopmental Disorders, its Mortality and Morbidity Statistics (MMS), Coding Tool and Reference Guide, Clinical Descriptions and Diagnostic Guidelines (CDDG), and other tools for translation and implementation offers an innovative approach for individualised diagnosis, treatment and care of people with mental disorders. For supporting the international process of implementation, WHO has installed an International Advisory Group for Training and Implementation of ICD-11 MBND. Development, Concept and Structure of ICD-11 will be presented. Selected changes from ICD-10 to ICD-11 like new diagnostic categories, revision of diagnostic criteria, introduction of dimensional symptom qualifiers or course descriptors, and options for complex coding with regard to their innovative strength, controversial potential and impact on diagnostics, treatment and care will be briefly discussed. National challenges for implementation - partly informed by international field trials, administrative, organisational, educational and training requirements - will be outlined. The new ICD-11 chapter on Schizophrenia or other primary psychotic disorders will serve as an example to discuss potential impact on treatment selection and outcome.DisclosureNo significant relationships.

Diabetes and Pregnancy: A Questionnaire Study on Clinical Management of Gestational Diabetes Mellitus and Pregnant Women with Diabetes Before and After the Revision of Diagnostic Criteria at Saiseikai Hospitals

Diabetes and Pregnancy: A Questionnaire Study on Clinical Management of Gestational Diabetes Mellitus and Pregnant Women with Diabetes Before and After the Revision of Diagnostic Criteria at Saiseikai Hospitals

Wilson disease: revision of diagnostic criteria in a clinical series with great genetic homogeneity.

Wilson disease is an autosomal recessive disorder of copper metabolism caused by mutations in the ATP7B gene. An early diagnosis is crucial to prevent evolution of the disease, as implantation of early therapeutic measures fully prevents its symptoms. As population genetics data predict a higher than initially expected prevalence, it was important to define the basic diagnostic tools to approach population screening. A highly genetically homogeneous cohort of 70 patients, belonging to 50 unrelated families, has been selected as a framework to analyze all their clinical, biochemical and genetic characteristics, to define the disease in our population, with an estimated prevalence of 1 in 12,369, and determine the most useful features that reach diagnostic value. Serum ceruloplasmin below 11.5mg/dL and cupremia below 60μg/mL, were the best analytical predictors of the disease in asymptomatic individuals, while cupruria or hepatic copper determination were less powerful. Genetic analysis reached a conclusive diagnosis in all 65 patients available for complete testing. Of them, 48 were carriers of at least one p.Leu708Pro mutant allele, with 24 homozygotes. Nine patients carried a promoter deletion mutation, revealing that extended sequencing beyond the ATP7B gene-coding region is essential. All mutations caused hepatic damage since early ages, increasing its severity as diagnosis was delayed, and neurological symptoms appear. Serum ceruloplasmin determination followed by genetic screening would reduce costs and favor the prioritization of non-invasive procedures to reach a definitive diagnosis, even for asymptomatic cases.

The effect of concomitant fibromyalgia in HIV infected patients receiving antiretroviral therapy: a prospective cross-sectional study

BackgroundHIV infected patients receiving antiretroviral therapy (ART) have extensive musculoskeletal system involvement. Arthralgia and myalgia are the most common forms. Fibromyalgia Syndrome (FMS) is a chronic pain syndrome of the musculoskeletal system characterized by diffuse pain including arthralgia and myalgia. These overlapping symptoms are suggested the relationship between HIV and FMS. The primary purpose of this study was to determine the prevalence of FMS in HIV/AIDS patients. The secondary objective was to investigate the effects of FMS on functional status, depression, fatigue, sleep pattern and quality of life.MethodsA total of 225 HIV infected patients who were receiving ART were included in this cross-sectional prospective study. The demographic data of the participants, CD4 T-lymphocyte count (cells/mm3), viral load (> 40 copy/ml), and ART regimens were recorded. FMS diagnosis was based on 2016 revision of diagnostic criteria. All patients completed the following questionnaires: Fibromyalgia Impact Questionnaire (FIQ), Beck Depression Inventory (BDI), Pittsburgh Sleep Quality Index (PSQI), Fatigue Severity Scale (FSS), and SF-36 scale.ResultsFMS was found in 20% of the HIV infected patients (n = 45). The mean duration of disease was 4.74 ± 4.42 years; it was significantly longer in patients with FMS (p = 0.007). The median CD4 T-lymphocyte count was found to be 616.00 ± 303.91 cells/mm3, and it was significantly higher in patients without FMS (p = 0.06). No statistically significant difference was found between the two groups according to the drug regimens used. A statistically significant difference was found in FIQ, BDI, PSQI, FSS and all subgroups of the SF-36 scale between the patients with and without FMS (p = 0.001).ConclusionsA slightly higher frequency of FMS was determined in HIV infected patients receiving ART compared to previous studies. It was shown that presence of FMS negatively affected the function, depression, fatigue, sleep, and quality of life. Detection of FMS may decrease depression, fatigue, and sleep disorders and increase the quality of life in HIV infected patients. FMS should be distinguished correctly for an accurate treatment management of HIV and for increasing ART compliance.

Update of the Diagnostic Criteria of J-Wave Syndrome: New Concepts and Their Relevance to Cardiology Practice (According to Materials of J-Wave Syndromes Expert Consensus Conference Report: Emerging Concepts and Gaps in Knowledge (2016)

This review includes main positions of the revision of diagnostic criteria of “J-wave syndromes in the J-Wave Syndromes Expert Consensus Conference Report: Emerging Concepts and Gaps in Knowledge” (2016). The article, systematized according to the sections of the above-mentioned document, outlines the questions of terminology, new criteria for diagnosis of the Brugada syndrome (BrS) and early repolarization syndrome (ERS). The section devoted to ERS on the issues of new terminology and standardization of measurements, is supplemented with material from the Consensus Paper - The Early Repolarization Pattern (2015). The article also presents the issues of differential diagnosis in BrS, presents modulating factors, defines acquired Brugada-pattern and Brugada phenocopies. The similarities and differences between BrS and ERS are presented in a comparative aspect.

The assessment and management of defecatory dysfunction: a critical appraisal.

To summarize the advances in diagnostic modalities and management options for defecatory dysfunction and highlight the areas in need of further research. The diagnostic utility of high-resolution anorectal manometry (ARM), which has emerged as a promising tool for the diagnosis of defecatory dysfunction, appears to be questionable in differentiating disease from normal physiology. There also seems to be discrepancy between results of various tests of anorectal function in the diagnosis of defecatory dysfunction. New revisions in diagnostic criteria for defecatory dysfunction by Rome IV consortium, may enhance its diagnostic yield. Biofeedback remains to be the most effective evidence-based treatment option for patients with defecatory dysfunction. Anorectal pressure profile cannot predict or mediate the success of biofeedback. Biofeedback may improve the symptoms through central effects. Despite the advances in the ARM and defecography techniques, no one test has been able to be considered as the 'gold standard' for diagnosis of defecatory dysfunction. The mechanism of action of biofeedback in defecatory dysfunction remains poorly understood.

The Role of Minimal Residual Disease Testing in Myeloma Treatment Selection and Drug Development: Current Value and Future Applications.

Treatment of myeloma has benefited from the introduction of more effective and better tolerated agents, improvements in supportive care, better understanding of disease biology, revision of diagnostic criteria, and new sensitive and specific tools for disease prognostication and management. Assessment of minimal residual disease (MRD) in response to therapy is one of these tools, as longer progression-free survival (PFS) is seen consistently among patients who have achieved MRD negativity. Current therapies lead to unprecedented frequency and depth of response, and next-generation flow and sequencing methods to measure MRD in bone marrow are in use and being developed with sensitivities in the range of 10-5 to 10-6 cells. These technologies may be combined with functional imaging to detect MRD outside of bone marrow. Moreover, immune profiling methods are being developed to better understand the immune environment in myeloma and response to immunomodulatory agents while methods for molecular profiling of myeloma cells and circulating DNA in blood are also emerging. With the continued development and standardization of these methodologies, MRD has high potential for use in gaining new drug approvals in myeloma. The FDA has outlined two pathways by which MRD could be qualified as a surrogate endpoint for clinical studies directed at obtaining accelerated approval for new myeloma drugs. Most importantly, better understanding of MRD should also contribute to better treatment monitoring. Potentially, MRD status could be used as a prognostic factor for making treatment decisions and for informing timing of therapeutic interventions. Clin Cancer Res; 23(15); 3980-93. ©2017 AACR.

Disease-modifying therapy for multiple sclerosis

ABSTRACT Remarkable expansion of new diagnostic criteria and disease-modifying treatments for multiple sclerosis has occurred in the last two decades. Revision of diagnostic criteria and characterization of disease course has allowed earlier diagnosis and better characterization of individual patients. With the current treatment armamentarium in the USA offering 11 agents, patients can now benefit from increasingly individualized therapy. The therapeutic decision-making process has become more complex, with the availability of multiple medications. Relative efficacy, potentially severe adverse events, tolerability issues and patient's preferences must now all be considered so that increasingly disease management more frequently involves physicians with multiple sclerosis subspecialty expertise. This article aims to provide a clinically oriented and concise review of currently available, as well as emerging, disease-modifying treatment therapies in multiple sclerosis.

What does it mean to be 'amyloid-positive'?

This scientific commentary refers to ‘Independent information from cerebrospinal fluid amyloid-β and florbetapir imaging in Alzheimer’s disease’ by Mattsson et al. (10.1093/brain/awu367). Studies of fluid and imaging biomarkers of Alzheimer’s disease have contributed greatly to our understanding of disease pathobiology, and in so doing have fuelled a paradigm shift in the conceptualization of Alzheimer’s disease as a chronic condition characterized by a long (∼10–20 year) preclinical phase during which hallmark pathologies develop, before the appearance of cognitive symptoms (dementia) clinically defined as Alzheimer’s disease. Revisions in diagnostic criteria to incorporate biomarker results have recently been proposed (Dubois et al. , 2010; Albert et al. , 2011; McKhann et al. , 2011; Sperling et al. , 2011) in order to increase confidence in identifying Alzheimer’s disease as the underlying aetiology of a clinical impairment and to permit a diagnosis across the disease continuum, eventually perhaps in the asymptomatic period. Biomarkers are currently being used in clinical trials for participant enrolment, evaluation of target engagement and as outcome measures (Hampel et al. , 2011). Thus, validation of Alzheimer’s disease biomarkers is of critical importance. In this issue of Brain , Mattsson and colleagues (2015) evaluate and compare two amyloid-related biomarkers—CSF levels of amyloid-β42 (the primary component of amyloid plaques) versus amyloid imaging via PET with florbetapir (AMYViD™), a radiolabelled tracer approved by the US Federal Drug Administration in 2012 for the detection of brain amyloid—in their ability to predict clinical diagnosis and other measures and features of Alzheimer’s disease (Mattsson et al. , 2015). Importantly, while the study confirms the previously reported diagnostic and prognostic utility of these two markers, the data expand upon previous results by exploring the discordance of these two measures in a large research cohort that spans the range of Alzheimer’s disease stages, …

Psychiatry's Integration with Medicine: The Role of DSM-5

Mental disorders represent a significant global burden whose effects are exacerbated by gaps in diagnosis and service provision. A substantial number of individuals seek services not through specialty psychiatric clinics but through primary care. Thus, the interface between psychiatry and the rest of medicine represents an appropriate area of focus in which to improve the detection and treatment of mental disorders. Development of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) can play a key role in this process. DSM-5 is expected to include specific revisions in diagnostic criteria, chapter organization, text structure, and classification approach that are designed to improve use of DSM by nonpsychiatrist physicians. Furthermore, revisions to DSM-5 will inform development of the primary care version of DSM-5. The goal is to publish a manual that enhances clinical utility in a manner that is concise and more amenable to use in primary care.

Personality Structures and Chronic Childhood Relational Trauma: Psychodynamic and Attachment based Perspectives that Challenge the Restricted Diagnosis of Personality Disorder

With the imminent publication of DSM V growing ever closer, the author suggests that headline diagnostic categories, such as narcissistic personality, histrionic personality or the ubiquitous borderline personality may actually be unhelpful to the clinician, who wishes to reach a deeper understanding of the factors shaping character pathology. The proposed revision of diagnostic criteria for personality disorder, in the forthcoming DSM V, to further emphasise traits within nosographical personality categories, appears to remain limited in conceptual scope. The psychoanalytic concept of personality structure is considered more malleable, from a conceptual perspective, in that it may enable the clinician to both describe and situate current psychological conflicts more appropriately, within a developmental context. It is suggested, in this paper, that such a conceptual progression is necessary in order to accommodate the rich seam of object relations, and attachment based approaches that have further shaped our understanding of personality development and personality difficulties, over the last two decades.

Atrichia with Papular Lesions: A Report of Three Novel Human Hairless Gene Mutations and a Revision of Diagnostic Criteria

Atrichia with papular lesions is a rare autosomal recessive condition characterized by complete irreversible hair loss during the first months of life and papules that appear during early childhood. Atrichia with papular lesions is frequently misdiagnosed as alopecia universalis, despite increasing reports of its prevalence and the presence of well-defined diagnostic criteria. Most cases of atrichia with papular lesions have been reported in consanguineous families residing in small geographical regions, but the increasing number of sporadic cases of unrelated individuals suggests that atrichia with papular lesions is more common than previously thought. Mutations in the human hairless gene on chromosome 8p12 have been implicated in this disease. Here, we report two novel heterozygous mutations in an Australian family and a novel homozygous mutation in 2 Arab siblings. We also revise the diagnostic criteria for atrichia with papular lesions in order to clarify its uniqueness and distinguishing features from alopecia universalis.

Prevalence of dissociative disorders among women in the general population

This study sought to determine the prevalence of dissociative disorders among women in the general population, as assessed in a representative sample of a city in central Turkey. The Dissociative Disorders Interview Schedule (DDIS), the Borderline Personality Disorder section of the Structured Clinical Interview for DSM-III-R Personality Disorders (SCID-II), and the PTSD-Module of the Structured Clinical Interview for DSM-III-R (SCID) were administered to 628 women in 500 homes. The mean age of participants was 34.8 (S.D. = 11.5, range: 18–65); 18.3% of participants ( n = 115) had a lifetime diagnosis of a dissociative disorder. Dissociative disorder not otherwise specified (DDNOS) was the most prevalent diagnosis (8.3%); 1.1% of the population was diagnosed as having dissociative identity disorder (DID). Participants with a dissociative disorder had borderline personality disorder, somatization disorder, major depression, PTSD, and history of suicide attempt more frequently than did participants without a dissociative disorder. Childhood sexual abuse, physical neglect, and emotional abuse were significant predictors of a dissociative disorder diagnosis. Only 28.7% of the dissociative participants had received psychiatric treatment previously. Because dissociative disorders are trauma-related, significant part of the adult clinical consequences of childhood trauma remains obscure in the minds of mental health professionals and of the overall community. Revisions in diagnostic criteria of dissociative disorders in the DSM-IV are recommended.

原発性胆汁性肝硬変診断基準の改訂について

原発性胆汁性肝硬変診断基準の改訂について

A critical review of caffeine withdrawal: empirical validation of symptoms and signs, incidence, severity, and associated features.

Although reports of caffeine withdrawal in the medical literature date back more than 170 years, the most rigorous experimental investigations of the phenomenon have been conducted only recently. The purpose of this paper is to provide a comprehensive review and analysis of the literature regarding human caffeine withdrawal to empirically validate specific symptoms and signs, and to appraise important features of the syndrome. A literature search identified 57 experimental and 9 survey studies on caffeine withdrawal that met inclusion criteria. The methodological features of each study were examined to assess the validity of the effects. Of 49 symptom categories identified, the following 10 fulfilled validity criteria: headache, fatigue, decreased energy/activeness, decreased alertness, drowsiness, decreased contentedness, depressed mood, difficulty concentrating, irritability, and foggy/not clearheaded. In addition, flu-like symptoms, nausea/vomiting, and muscle pain/stiffness were judged likely to represent valid symptom categories. In experimental studies, the incidence of headache was 50% and the incidence of clinically significant distress or functional impairment was 13%. Typically, onset of symptoms occurred 12-24 h after abstinence, with peak intensity at 20-51 h, and for a duration of 2-9 days. In general, the incidence or severity of symptoms increased with increases in daily dose; abstinence from doses as low as 100 mg/day produced symptoms. Research is reviewed indicating that expectancies are not a prime determinant of caffeine withdrawal and that avoidance of withdrawal symptoms plays a central role in habitual caffeine consumption. The caffeine-withdrawal syndrome has been well characterized and there is sufficient empirical evidence to warrant inclusion of caffeine withdrawal as a disorder in the DSM and revision of diagnostic criteria in the ICD.

The changing face of migraine.

Migraine is a major source of pain-related disability. Despite the personal and societal impact of this disorder, migraine continues to be misdiagnosed and undertreated even though well-established diagnostic criteria and safe and effective treatments are available. The recent revision of diagnostic criteria for headache diagnosis and consensus guidelines for migraine treatment hopefully will promote better medical care for headache sufferers. Advancements in understanding the neurobiology of migraine will guide the development of new treatments.