Framingham Risk Stratification of Middle-Aged Migraineurs.

Introduction. Migraine is a common primary headache disorder involving about 10-15% of the whole population. Several epidemiological and prospective studies showed a link between migraine (especially migraine with aura) and cardio- and cerebrovascular events. OBJECTIVES: We prospectively analyzed the data of vascular event-free middle-aged patients with migraine who were referred to our Headache Clinic between 01/2014 and 01/2018. Framingham 10-year risk were calculated; covariates included in the analysis were age, total cholesterol, HDL cholesterol, systolic blood pressure, antihypertensive medication use, current smoking, and diabetes status. RESULTS: Total of 1037 patients were screened and 221 were selected, 161 were women (mean age 55.5 ± 5.2 years) and 60 were men (mean age 56 ± 6 years). 25 patients (11.3%) were labelled as having low risk, 162 patients (73.3%) had moderate risk, and 34 patients (15.4%) had high or very high risk. Blood pressure and lipid targets were reached in 73% and in 49% in the moderate risk and in 53% and 12% in the high risk/very high risk groups, respectively. Migraine with aura (MA) was associated significantly higher cardiovascular risk profile compared with migraine without aura (MO). About one-third of our nondiabetic patients had fasting blood glucose above the normal levels. 24 patients (mean age 60 ± 4.9 years) were diabetic. Mean blood pressure was 149/85 Hgmm, mean choleterol was 5.11 mmol/l, and mean LDL was 2.93 mmol/l in this subgroup, respectively, which do not fall within the recommended targets. CONCLUSION: Our article draws attention to the higher cardiovascular risk profile of middle-aged migraineurs and highlights the deficiency of primary prevention. Pain physicians must be aware of the cardiovascular aspects of migraine and holistic approach is required instead of focusing only on pain and pain relief.

ICHD-3 is significantly more specific than ICHD-3 beta for diagnosis of migraine with aura and with typical aura.

BACKGROUND: In the emergency room, distinguishing between a migraine with aura and a transient ischemic attack (TIA) is often not straightforward and mistakes can be harmful to both the patient and to society. To account for this difficulty, the third edition of the International Classification of Headache disorders (ICHD-3) changed the diagnostic criteria of migraine with aura. METHODS: One hundred twenty-eight patients referred to the emergency room at the University Hospital of Lübeck, Germany with a suspected TIA were prospectively interviewed about their symptoms leading to admission shortly after initial presentation. The diagnosis that resulted from applying the ICHD-3 and ICHD-3 beta diagnostic criteria was compared to the diagnosis made independently by the treating physicians performing the usual diagnostic work-up. RESULTS: The new ICHD-3 diagnostic criteria for migraine with aura and migraine with typical aura display an excellent specificity (96 and 98% respectively), and are significantly more specific than the previous ICHD-3 beta classification system when it comes to diagnosing a first single attack (probable migraine with aura and probable migraine with typical aura). CONCLUSIONS: The ICHD-3 is a highly useful tool for the clinical neurologist in order to distinguish between a migraine with aura and a TIA, already at the first point of patient contact, such as in the emergency department or a TIA clinic.

What Are We Missing in the Diagnostic Criteria for Migraine?

PURPOSE OF REVIEW: This review is intended to examine how the diagnostic criteria for migraine have evolved over the past 45 years and to evaluate the strengths and weaknesses of the current diagnostic criteria promulgated by the International Classification of Headache Disorders (ICHD). RECENT FINDINGS: The ICHD is a comprehensive and systematic classification system for headache disorders. As the pathophysiology of migraine is more fully elucidated and more sophisticated diagnostic technologies are developed (e.g., the identification of biomarkers), the current diagnostic criteria for migraine will likely be further refined. The ICHD has allowed for more precise research study design in the field of headache medicine. The current diagnostic criteria for migraine outlined in the 3rd version of the ICHD are far more sensitive and specific than the clinical criteria proposed in 1962. In future iterations, dividing episodic and chronic migraine into subtypes based on frequency (i.e., low frequency vs high frequency; near-daily vs daily) potentially could assist in guiding clinical management. In addition, a better understanding of aura, vestibular migraine, migrainous infarction, and hemiplegic migraine likely will lead to more refined diagnostic criteria for those entities.

Explicit diagnostic criteria for transient ischemic attacks to differentiate it from migraine with aura.

Background The diagnosis of transient ischemic attacks is fraught with problems. The inter-observer agreement has repeatedly been shown to be low even in a neurological setting, and the specificity of the diagnosis is modest to low, reflected in a poor separation of transient ischemic attacks and mimics, particularly migraine with aura with its varied symptomatology. In other disease areas, explicit diagnostic criteria have improved sensitivity and specificity of diagnoses. We therefore present novel explicit diagnostic criteria for transient ischemic attacks tested for sensitivity and for specificity against migraine with aura. Methods The proposed criteria were developed using the format of the international headache classification. We drew upon the existing literature about clinical characteristics and diagnosis of migraine with aura and transient ischemic attacks. We tested the criteria for sensitivity in a prospectively-collected material of 120 patients with transient ischemic attacks diagnosed before we developed the criteria using extensive semi-structured interview forms in the acute phase after admission. Eligible patients had focal brain or retinal ischemia with resolution of symptoms within 24 hours without presence of new infarction on magnetic resonance imaging with diffusion weighted imaging (n = 112) or computed tomography (n = 8). These criteria were also tested for specificity against a Danish (n = 1390) and a Russian (n = 152) material of patients with migraine with aura diagnosed according to the International Classification of Headache Disorders edition 3 (beta). Results The sensitivity of the proposed criteria was 99% in patients with transient ischemic attacks. The specificity was 95% in the Danish material of patients with migraine with aura and 96% in the Russian material. Conclusions Proposed explicit diagnostic criteria for transient ischemic attacks showed both high specificity and sensitivity. They are likely to improve the emergency room diagnosis of transient ischemic attacks. Further testing in unselected materials referred to transient ischemic attacks clinics was beyond the scope of the present study but is recommended for future study.

Features of aura in paediatric migraine diagnosed using the ICHD 3 beta criteria.

Background In children and adolescents, the prevalence rate of migraine with aura is 1.6%. Few studies concerning migraine with aura features in paediatric population have been reported. Aim The aim of our study was to investigate clinical features of aura in a retrospective cohort of children with migraine with aura. Furthermore, we studied whether the International Classification of Headache Disorder (ICHD) 3 beta version criteria could efficiently detect migraine with aura in a paediatric population. Results We included 164 patients who experienced aura associated with headache (mean age 9.92 ± 2.64 years). When the ICHD-II criteria were used, a final diagnosis of migraine with typical aura was obtained in 15.3% of patients, probable migraine with typical aura in 13.4%, and typical aura with headache in 61.8%, while in in 9.5% of patients the diagnosis was undetermined. According to ICHD-3 beta, we diagnosed migraine with typical aura in 77.7% of patients, probable migraine with typical aura in 13.4%, and an undetermined diagnosis in 9.5% (less than two attacks). Conclusion Aura features did not depend on age and were similar to those of adults. However, the headache could be difficult to classify if headache duration was considered. In this view, the ICHD-3 beta offers the advantage of not considering headache features, including pain duration, for the diagnosis of migraine with typical aura, thus making this diagnosis easier in children and adolescents.

Migraine aura: new ideas about cause, classification, and clinical significance.

PURPOSE OF REVIEW: The migraine aura is a dramatic spontaneous change in brain activity resulting in a variety of transient neurological symptoms. The purpose of this review is to address recent advances in the understanding of aura and its role in migraine. RECENT FINDINGS: The formal classification of migraine aura is becoming both broader and more detailed. Traditionally viewed as a primary event that triggers a migraine attack, studies regarding the timing of aura relative to other symptoms of migraine indicate that it may not in fact play a primary role in initiating an attack. Careful recording and analysis of visual aura symptoms provides new insight into the initiation and propagation of the underlying brain phenomenon, and the different regions of visual cortex that produce different visual perceptions. Migraine with aura may have different responses to acute and preventive therapies. SUMMARY: There has been significant evolution of concepts regarding the causes of migraine aura, how it is best defined, and how it fits into the picture of the migraine disorder as a whole. Regardless of its exact role in the genesis of migraine, an increased understanding of aura has the potential to provide important new insight into not only migraine but also fundamental mechanisms of brain physiology.

Typical aura without headache: a case report and review of the literature.

INTRODUCTION: Typical aura without headache (TAWH), which has been rarely reported both at home and abroad, is a rare type of migraine with aura. CASE PRESENTATION: This is a report on a 64-year-old Chinese migraineur who has had recurrent typical visual aura without headache attacks for more than 30 years, and has been misdiagnosed as having had transient ischemic attacks (TIA) many times. He mainly experienced episodes of 'homonymous blurred vision' or photopsia, which presented as different shapes located at the side or above his visual field, for example, patchy, cord-like, zigzag, curtain-like or irregular shapes. The shape was inconsistent during each attack, however, the color was mainly gray or light blue. The visual symptoms gradually disappeared in about 30 minutes. Our patient has never suffered a headache attack during or after the visual aura. Normal results were observed in his neurological and eye examinations, complete blood test, electroencephalogram and neuroimaging examination. CONCLUSIONS: TAWH is an uncommon phenomenon of migraine. Migraine with visual aura mainly presents positive and dynamic symptoms. It has a benign course and can be diagnosed after exclusion of other organic diseases such as TIA and epilepsy.

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

INTRODUCTION: In 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 present proposed version of the International Classification of Diseases (ICD-11), although slightly abbreviated to fulfill the needs of ICD-11. In the following, only ICHD-3 beta is mentioned, but findings regarding the validity of ICHD-3 beta categories are equally relevant to the forthcoming ICD-11. Here we field-tested the criteria for 1.2 migraine with aura (MA), 1.2.1 migraine with typical aura (MTA), 1.2.3 hemiplegic migraine, 1.2.2 migraine with brainstem aura, and the alternative criteria A1.2 MA and A1.2.1 MTA. METHODS: Clinical characteristics were systematically and prospectively collected from patients with 1.2.1 MTA, 1.2.4 familial hemiplegic migraine (FHM), 1.2.5 sporadic hemiplegic migraine (SHM) and 1.2.6 basilar-type migraine according to ICHD-2 in a cross-sectional study design. A database of 2464 patients with 1.1 migraine without aura and 1.2 migraine with non-hemiplegic aura and a database of 252 hemiplegic migraine patients (1.2.4 FHM or 1.2.5 SHM) was collected. We used SPSS 20 for Windows 8.0 for the statistical analysis. RESULTS: All ICHD-2 patients fulfilled ICHD-3 beta criteria for 1.2 MA. The ICHD-3 beta criteria for 1.2.1 MTA were more sensitive than ICHD-2 and ICHD-3 beta alternative criteria; they resulted in fewer probable MA diagnoses. Too many patients fulfilled ICHD-2 and ICHD-3 beta criteria for 1.2.2 migraine with brainstem aura. ICHD-3 beta criteria for 1.2.4 FHM and 1.2.5 SHM both comply with ICHD-2. CONCLUSION: The new criteria in ICHD-3 beta/proposed ICD-11 for 1.2 MA, 1.2.1 MTA, 1.2.3.1 FHM and 1.2.3.2 SHM have more desirable properties than ICHD-2 and the ICHD-3 beta alternative criteria. The criteria for 1.2.2 migraine with brainstem aura should be more restrictive.

Aura status: a not so frequent aura.

BACKGROUND: Migraine aura status is a variety of migraine aura with unvalidated research criteria. AIM AND METHODS: We conducted a systematic review of published cases and a retrospective analysis of 500 cases of migraine with aura to evaluate the applicability and clinical features of ICHD-III beta criteria, compared to a more liberal definition for its diagnosis: ≥3 aura episodes for up to three consecutive days. RESULTS: Many publications under this title correspond to persistent or formerly designated prolonged auras. Nine cases fulfilled ICHD-III beta status criteria. In our series, either 1.7% or 4.2% cases fulfilled ICDH-III beta or our definition, respectively. Regardless of the criteria, aura status patients were older at onset of status than those with typical aura, had a predominance of visual symptoms, normal neuroimaging and no sequelae. Status recurred in a few. CONCLUSION: Both criteria identify a similar population in terms of age, gender, main symptoms, imaging and outcome. Since patients with closely recurring auras might raise the same approach independently of the criteria, the use of more liberal criteria will allow more cases for detailed diagnosis and therapeutic analysis, eventually leading to the identification of subtypes.

[Migraine: ignition of the brain]. / Migraña: la ignición del cerebro.

Although our knowledge of which systems are activated during migraine is reasonably complete, why the system is activated remains unknown. Incorporating the findings obtained in studies on pain in general has allowed a more integrated model to be generated. According to this new model, there is an anatomical substrate consisting in a complex framework of pain that is made up not only of the trigeminovascular system (end pathway) but of a number of networks that are in turn connected to one another, like the neurolimbic, the ascending and descending modulatory system. This complex network is responsible for modulating and conveying nociceptive signals. In patients with migraine, hyperexcitability of this framework is conditioned by genetic and epigenetic alterations. Epigenetic changes are chemical modifications affecting chromatin, which modulates the activity of genes without modifying the DNA sequence, and which are capable of modulating the expression of genes involved in a number of different aspects, such as plasticity, system excitability, memory of pain or moods. In turn, the presence of external factors (such as environmental changes or alcohol) and internal factors (such as hormones or sleep disorders) contribute to activate this loaded anatomical substrate, resulting in the attack of migraine.

TITLE: Migraña: la ignicion del cerebro.Aunque se sabe razonablemente bien que sistemas se activan durante la migraña, el porque se activa el sistema sigue siendo un gran desconocido. Gracias a la integracion de hallazgos obtenidos en estudios de dolor en general se genera un modelo mas integrador. Segun este nuevo modelo, existe un sustrato anatomico constituido por un complejo entramado de dolor que no solo esta formado por el sistema trigeminovascular (via final) sino por multiples redes que a su vez estan comunicadas entres si como es el sistema neurolimbico, sistema modulador ascendente y descendente. Esta compleja red es la encargada de modular y vehicular la señal nociceptiva. En pacientes con migraña, la hiperexcitabilidad de este entramado esta condicionada por alteraciones geneticas y epigeneticas. Los cambios epigeneticos son modificaciones quimicas de la cromatina que modula la actividad de los genes sin modificar la secuencia de ADN y que son capaces de modular la expresion de genes involucrados en multiples aspectos: plasticidad, excitabilidad del sistema, memoria del dolor o estados animicos. A su vez, la presencia de factores externos (como cambios ambientales o el alcohol) y factores internos (como hormonas o alteracion del sueño) contribuye a que este sustrato anatomico que esta cargado se active y desemboque en el ataque de migraña.

[Genetics of migraine]. / Génétique de la migraine.

The aim of genetic studies in migraine is to identify key proteins in order to better understand the molecular mechanisms of this frequent but still incompletely understood condition. This review describes the current knowledge in the field of migraine genetics. Migraine genes have been, and still are, difficult to identify. The more common varieties of migraine are characterized by a high prevalence in the general population, and a high phenotypic variability. In the absence of any objective diagnosis marker, the status for genetic studies is established only clinically. The first breakthrough was permitted by the study of familial hemiplegic migraine, a variety of migraine with motor aura. This rare condition has a monogenic, autosomal dominant mode of inheritance, thus enabling genetic studies. The three first genes, identified from 1996 to 2005, all encode ion-channel transporters: a neuronal calcium channel (CACNA1A, FHM1), a glial sodium/potassium pump (ATP1A2, FHM2) and a neuronal sodium channel (SCN1A, FHM3). Study of cellular and animal models have shown that mutations in CACNA1A and ATP1A2 facilitated the initiation of cortical spreading depression waves, the mechanism underlying the migraine aura, and most likely increased neuronal excitability with an excess of glutamatergic neurotransmission. In 2012, PRRT2 has been identified as the fourth FHM gene, and encodes an axonal protein associated to the exocytosis complex. In the 1990s, family and twin studies showed that the more common varieties of migraine (migraine without aura and migraine with typical aura) were polygenic, with an overall heritability nearing 50 %. These genetic factors interact with environmental factors. The initial attempts to identify migraine genes by candidate gene approaches or by linkage studies were deceiving. Since 2010, three large genome-wide association studies (GWAS) have identified six genetic variants associated with migraine. Each variant has only a modest contribution to the overall genetic risk of migraine, suggesting a marked genetic heterogeneity. Three of the migraine-associated variants affect genes involved in glutamate homeostasis. Another variant concerns a gene encoding a protein implicated in nociception. Three of the four polymorphisms are associated both with migraine without aura and migraine with aura, supporting the existence of molecular mechanisms shared by all varieties of migraine. The vast majority of the migraine genes are still to be identified. Future researches will rely on new GWAS on larger cohorts of patients and controls, with a better phenotypic assessment, and on extensive sequencing.

Treatment strategies for menstrually related migraine.

Approximately 50% of migrainous women suffer from menstrually related migraine (MRM), a type of migraine in which the attacks occur at the same time as or near the menstrual flow. Attacks of MRM tend to be longer, more intense and disabling and sometimes less responsive to treatment than non-menstrual migraines. Similar to the management of non-menstrual migraine, the use of triptans and NSAIDs is the gold standard for MRM treatment. In this paper, the most important studies in the literature that report the effectiveness of triptans, of certain associated drugs and other analgesic agents are summarized. Preventive strategies that can be used if a prophylactic treatment is needed is also analyzed, with particular attention paid to the use of perimenstrual prophylaxis with triptans and/or NSAIDs. Moreover, considering the peculiar interaction between menstrual migraine and female sex hormones, brief mention is made to possible hormonal manipulations.

ICHD-3: what changes do we need regarding migraine?

Based on publications on migraine in the medical literature after 2004, the third edition of the International Classification of Headache Disorders (ICHD-3), with publication date early in 2013, will provide a framework to systematize those migraine forms that the second edition (ICHD-2) included in its Appendix. The most needed changes concern so-called chronic migraine. The revised ICHD-2 (ICHD-2R) did introduce appreciable changes to the ICHD-2 diagnostic criteria for chronic migraine. To be more relevant to actual clinical practice, the classification should discriminate between forms of migraine without aura depending on low, medium, or high frequency of attacks. The classification should include transformed migraine, an appellation that seems preferable to chronic migraine, in the group of migraine complications using extended time parameters compared with those currently used in ICHD-2R for chronic migraine. Finally, it should assess the opportunity of a different classification for medication-overuse headache.

Migraine and sleep apnea in the general population.

Objective is to investigate the relationship between migraine and obstructive sleep apnea in the general population. A cross-sectional population-based study. A random age and gender stratified sample of 40,000 persons aged 20-80 years residing in Akershus, Hedmark or Oppland County, Norway, were drawn by the National Population Register. A postal questionnaire containing the Berlin Questionnaire was used to classify respondents to be of either high or low risk of obstructive sleep apnea. 376 persons with high risk and 157 persons with low risk of sleep apnea aged 30-65 years were included for further investigations. They underwent an extensive clinical interview, a physical and a neurological examination by physicians, and in-hospital polysomnography. Those with apnea hypopnoea index (AHI) ≥5 were classified with obstructive sleep apnea. Migraine without aura (MO) and migraine with aura (MA) was diagnosed according to the International Classification of Headache Disorders. MO and MA occurred in 12.5 and 6.8% of the participants with obstructive sleep apnea. The logistic regression analyses showed no relationship between the two types of migraine and obstructive sleep apnea, with adjusted odds ratios for MO 1.15 (0.65-2.06) and MA 1.15 (0.95-2.39). Further, estimates using cutoff of moderate (AHI ≥ 15) and severe (AHI ≥ 30) obstructive sleep apnea, did not reveal any significant relationship between migraine and the AHI. Migraine and obstructive sleep apnea are unrelated in the general population.

Familial hemiplegic migraine.

Familial hemiplegic migraine (FHM) is a rare, dominantly inherited subtype of migraine with aura, where hemiplegia occurs during the aura phase. Mutation screening of families with FHM has revealed a range of different mutations. The mutated FHM genes code for ion transport proteins. Animal and cellular studies have associated the mutated FHM genes with disturbed ion homeostasis, altered cellular excitability and altered neurotransmitter release. Abnormal cortical excitability due to dysfunctional ion-channels might facilitate cortical spreading depression (CSD) and thereby migraine aura and migraine headache. Genotyped FHM patients offer us the chance to study the interplay between genotype and phenotype and may be regarded as a genetic migraine model. FHM studies might open for a better understanding of the molecular migraine pathology, and potentially help to unravel the pathogenesis of the more common migraine forms. We have therefore studied genotyped FHM patients to understand the effect of genotype on the response to migraine provoking substances. We show here that two known migraine triggers failed to induce more migraine aura or migraine headache in FHM-patients than in healthy controls, thus indicating that the FHM genotype does not confer hypersensitivity to these migraine triggers. This has implications for our understanding of the headache mechanisms and raises the question whether FHM share neurobiological background with the common types of migraine. The aims of the present thesis were to test the hypothesis that FHM mutations might be associated with hypersensitivity to known migraine triggers and, thereby, share pathophysiological pathways with the common types of migraine, but our results disprove this hypothesis. Thus, FHM seems very different from MO and MA, both genetically and pathophysiologically. The fact that FHM genes regulate ion homeostasis cannot be extrapolated to the common types of migraine.