Long-term safety of OnabotulinumtoxinA treatment in chronic migraine patients: a five-year retrospective study.

Background: Real-world studies have shown the sustained therapeutic effect and favourable safety profile of OnabotulinumtoxinA (BoNTA) in the long term and up to 4 years of treatment in chronic migraine (CM). This study aims to assess the safety profile and efficacy of BoNTA in CM after 5 years of treatment in a real-life setting. Methods: We performed a retrospective chart review of patients with CM in relation to BoNTA treatment for more than 5 years in 19 Spanish headache clinics. We excluded patients who discontinued treatment due to lack of efficacy or poor tolerability. Results: 489 patients were included [mean age 49, 82.8% women]. The mean age of onset of migraine was 21.8 years; patients had CM with a mean of 6.4 years (20.8% fulfilled the aura criteria). At baseline, patients reported a mean of 24.7 monthly headache days (MHDs) and 15.7 monthly migraine days (MMDs). In relation to effectiveness, the responder rate was 59.1% and the mean reduction in MMDs was 9.4 days (15.7 to 6.3 days; p < 0.001). The MHDs were also reduced by 14.9 days (24.7 to 9.8 days; p < 0.001). Regarding the side effects, 17.5% experienced neck pain, 17.3% headache, 8.5% eyelid ptosis, 7.5% temporal muscle atrophy and 3.2% trapezius muscle atrophy. Furthermore, after longer-term exposure exceeding 5 years, there were no serious adverse events (AE) or treatment discontinuation because of safety or tolerability issues. Conclusion: Treatment with BoNTA led to sustained reductions in migraine frequency, even after long-term exposure exceeding 5 years, with no evidence of new safety concerns.

Migraine treatment consensus document of the Spanish Society of Neurology (SEN), Spanish Society of Family and Community Medicine (SEMFYC), Society of Primary Care Medicine (SEMERGEN) and Spanish Association of Migraine and Headache (AEMICE) on migraine treatment. / Documento de consenso de la Sociedad Española de Neurología (SEN), Sociedad Española de Medicina de Familia y Comunitaria (SEMFYC), Sociedad de Medicina de Atención Primaria (SEMERGEN) y Asociación Española de Migraña y Cefalea (AEMICE) sobre el tratamiento de la migraña.

Migraine is a disease with a high prevalence and incidence, in addition to being highly disabling, causing a great impact on the patient's quality of life at a personal, family and work level, but also social, given its high expense due to its direct (care) and indirect (presenteeism and work absenteeism) costs. The multiple and recent developments in its pathophysiological knowledge and in its therapy require updating and, therefore, in this article the Spanish scientific societies most involved in its study and treatment (SEN, SEMFYC and SEMERGEN), together with the Association Spanish Association for Patients with Migraine and other Headaches (AEMICE), we have developed these updated care recommendations. We reviewed the treatment of migraine attacks, which consisted mainly of the use of NSAIDs and triptans, to which ditans and gepants have been added. We also discuss preventive treatment consisting of oral preventive drugs, botulinum toxin, and treatments that block the action of calcitonin-related peptide (CGRP). Finally, we emphasize that pharmacological treatments must be complementary to carrying out general measures consisting of identifying and managing/deletion the precipitating factors of the attacks and the chronicizing factors, controlling the comorbidities of migraine and eliminating analgesic overuse.

RE-START: Exploring the effectiveness of anti-calcitonin gene-related peptide resumption after discontinuation in migraine.

BACKGROUND AND PURPOSE: According to the latest European guidelines, discontinuation of monoclonal antibodies against calcitonin gene-related peptide (anti-CGRP MAb) may be considered after 12-18 months of treatment. However, some patients may worsen after discontinuation. In this study, we assessed the response following treatment resumption. METHODS: This was a prospective study conducted in 14 Headache Units in Spain. We included patients with response to anti-CGRP MAb with clinical worsening after withdrawal and resumption of treatment. Numbers of monthly migraine days (MMD) and monthly headache days (MHD) were obtained at four time points: before starting anti-CGRP MAb (T-baseline); last month of first treatment period (T-suspension); month of restart due to worsening (T-worsening); and 3 months after resumption (T-reintroduction). The response rate to resumption was calculated. Possible differences among periods were analysed according to MMD and MHD. RESULTS: A total of 360 patients, 82% women, with a median (interquartile range [IQR]) age at migraine onset of 18 (12) years. The median (IQR) MHD at T-baseline was 20 (13) and MMD was 5 (6); at T-suspension, the median (IQR) MHD was 5 (6) and MMD was 4 (5); at T-worsening, the median (IQR) MHD was 16 (13) and MMD was 12 (6); and at T-reintroduction, the median (IQR) MHD was 8 (8) and MHD was 5 (5). In the second period of treatment, a 50% response rate was achieved by 57.4% of patients in MHD and 65.8% in MMD. Multivariate models showed significant differences in MHD between the third month after reintroduction and last month before suspension of first treatment period (p < 0.001). CONCLUSION: The results suggest that anti-CGRP MAb therapy is effective after reintroduction. However, 3 months after resumption, one third of the sample reached the same improvement as after the first treatment period.

Effectiveness and safety of anti-CGRP monoclonal antibodies in patients over 65 years: a real-life multicentre analysis of 162 patients.

BACKGROUND: Anti-CGRP monoclonal antibodies have shown notable effectiveness and tolerability in migraine patients; however, data on their use in elderly patients is still lacking, as clinical trials have implicit age restrictions and real-world evidence is scarce. In this study, we aimed to describe the safety and effectiveness of erenumab, galcanezumab and fremanezumab in migraine patients over 65 years old in real-life. METHODS: In this observational real-life study, a retrospective analysis of prospectively collected data from 18 different headache units in Spain was performed. Migraine patients who started treatment with any anti-CGRP monoclonal antibody after the age of 65 years were included. Primary endpoints were reduction in monthly migraine days after 6 months of treatment and the presence of adverse effects. Secondary endpoints were reductions in headache and medication intake frequencies by months 3 and 6, response rates, changes in patient-reported outcomes and reasons for discontinuation. As a subanalysis, reduction in monthly migraine days and proportion of adverse effects were also compared among the three monoclonal antibodies. RESULTS: A total of 162 patients were included, median age 68 years (range 65-87), 74.1% women. 42% had dyslipidaemia, 40.3% hypertension, 8% diabetes, and 6.2% previous cardiovascular ischaemic disease. The reduction in monthly migraine days at month 6 was 10.1 ± 7.3 days. A total of 25.3% of patients presented adverse effects, all of them mild, with only two cases of blood pressure increase. Headache and medication intake frequencies were significantly reduced, and patient-reported outcomes were improved. The proportions of responders were 68%, 57%, 33% and 9% for reductions in monthly migraine days ≥ 30%, ≥ 50%, ≥ 75% and 100%, respectively. A total of 72.8% of patients continued with the treatment after 6 months. The reduction in migraine days was similar for the different anti-CGRP treatments, but fewer adverse effects were detected with fremanezumab (7.7%). CONCLUSIONS: Anti-CGRP mAbs are safe and effective treatments in migraine patients over 65 years old in real-life clinical practice.

MAB-MIG: registry of the spanish neurological society of erenumab for migraine prevention.

BACKGROUND: Erenumab was approved in Europe for migraine prevention in patients with ≥ 4 monthly migraine days (MMDs). In Spain, Novartis started a personalized managed access program, which allowed free access to erenumab before official reimbursement. The Spanish Neurological Society started a prospective registry to evaluate real-world effectiveness and tolerability, and all Spanish headache experts were invited to participate. We present their first results. METHODS: Patients fulfilled the ICHD-3 criteria for migraine and had ≥ 4 MMDs. Sociodemographic and clinical data were registered as well as MMDs, monthly headache days, MHDs, prior and concomitant preventive treatment, medication overuse headache (MOH), migraine evolution, adverse events, and patient-reported outcomes (PROs): headache impact test (HIT-6), migraine disability assessment questionnaire (MIDAS), and patient global improvement change (PGIC). A > 50% reduction of MMDs after 12 weeks was considered as a response. RESULTS: We included 210 patients (female 86.7%, mean age 46.4 years old) from 22 Spanish hospitals from February 2019 to June 2020. Most patients (89.5%) suffered from chronic migraine with a mean evolution of 8.6 years. MOH was present in 70% of patients, and 17.1% had migraine with aura. Patients had failed a mean of 7.8 preventive treatments at baseline (botulinum toxin type A-BoNT/A-had been used by 95.2% of patients). Most patients (67.6%) started with erenumab 70 mg. Sixty-one percent of patients were also simultaneously taking oral preventive drugs and 27.6% were getting simultaneous BoNT/A. Responder rate was 37.1% and the mean reduction of MMDs and MHDs was -6.28 and -8.6, respectively. Changes in PROs were: MIDAS: -35 points, HIT-6: -11.6 points, PIGC: 4.7 points. Predictors of good response were prior HIT-6 score < 80 points (p = 0.01), ≤ 5 prior preventive treatment failures (p = 0.026), absence of MOH (p = 0.039), and simultaneous BoNT/A treatment (p < 0.001). Twenty percent of patients had an adverse event, but only two of them were severe (0.9%), which led to treatment discontinuation. Mild constipation was the most frequent adverse event (8.1%). CONCLUSIONS: In real-life, in a personalized managed access program, erenumab shows a good effectiveness profile and an excellent tolerability in migraine prevention in our cohort of refractory patients.

Cutaneous Allodynia in Migraine: A Narrative Review.

OBJECTIVE: In the present work, we conduct a narrative review of the most relevant literature on cutaneous allodynia (CA) in migraine. BACKGROUND: CA is regarded as the perception of pain in response to non-noxious skin stimulation. The number of research studies relating to CA and migraine has increased strikingly over the last few decades. Therefore, the clinician treating migraine patients must recognize this common symptom and have up-to-date knowledge of its importance from the pathophysiological, diagnostic, prognostic and therapeutic point of view. METHODS: We performed a comprehensive narrative review to analyze existing literature regarding CA in migraine, with a special focus on epidemiology, pathophysiology, assessment methods, risk for chronification, diagnosis and management. PubMed and the Cochrane databases were used for the literature search. RESULTS: The prevalence of CA in patients with migraine is approximately 60%. The mechanisms underlying CA in migraine are not completely clarified but include a sensitization phenomenon at different levels of the trigemino-talamo-cortical nociceptive pathway and dysfunction of brainstem and cortical areas that modulate thalamocortical inputs. The gold standard for the assessment of CA is quantitative sensory testing (QST), but the validated Allodynia 12-item questionnaire is preferred in clinical setting. The presence of CA is associated with an increased risk of migraine chronification and has therapeutic implications. CONCLUSIONS: CA is a marker of central sensitization in patients with migraine that has been associated with an increased risk of chronification and may influence therapeutic decisions.

Headaches During COVID-19: My Clinical Case and Review of the Literature.

OBJECTIVE: To analyze headaches related to COVID-19 based on personal case experience. BACKGROUND: COVID-19 is an infection caused by the new coronavirus SARS-CoV-2. The first reported case happened in Wuhan on December 1, 2019. At present, at least 1.8 million people are infected around the world and almost 110,000 people have died. Many studies have analyzed the clinical picture of COVID-19, but they are focused on respiratory symptoms and headache is generically treated. METHODS: I describe and discuss my headaches during my COVID-19 and I review the MEDLINE literature about headaches and COVID-19. RESULTS: More than 41,000 COVID-19 patients have been included in clinical studies and headache was present in 8%-12% of them. However, no headache characterization was made in these studies. As a headache expert and based on my own personal clinical case, headaches related to COVID-19 can be classified in the 2 phases of the disease. Acute headache attributed to systemic viral infection, primary cough headache, tension-type headache and headache attributed to heterophoria can appear in the first phase (the influenza-like phase); and headache attributed to hypoxia and a new headache, difficult to fit into the ICHD3, can appear if the second phase (the cytokine storm phase) occurs. CONCLUSIONS: Several headaches can appear during COVID-19 infection. All of them are headaches specified in the ICHD3, except 1 that occurs from the 7th day after the clinical onset. This headache is probably related to the cytokine storm that some patients suffer and it could be framed under the ICHD3 headache of Headache attributed to other non-infectious inflammatory intracranial disease. Although the reported prevalence of headaches as a symptom of COVID-19 infection is low, this experience shows that, very probably, it is underestimated.

Efficacy and safety of surgical treatment of cluster headache. / Eficacia y seguridad del tratamiento quirúrgico en la cefalea en racimos.

BACKGROUND AND OBJECTIVES: Cluster headache (CR) is the most severe human headache and is chronic in 10%-20% of patients, and 10% can become refractory to all effective drugs. In this scenario, surgical procedures are indicated: radiofrequencies of the sphenopalatine ganglion ipsilateral to pain (RF-SPG), bilateral stimulation of the occipital nerves (NOM-S) and deep brain stimulation (DBS) of the ipsilateral posterior hypothalamus. The efficacy and safety of each of these procedures has been specifically analyzed, but the progress of a series of patients following this surgical route in order of aggressiveness has not been described. PATIENTS: Patients with chronic and refractory CR according to the criteria of the European Headache Federation. The patients underwent RF-SPG, NOM-S sequentially if the previous procedure had been ineffective, and DBS if the previous procedure had been ineffective. RESULTS: We prospectively included 44 patients between November 2003 and June 2018 with an average age of 38.3 years; 70% were men. The mean follow-up was 87.4 months. Nineteen patients responded to 74 procedures of RF-SPG (33.3%). Of the remaining 25 patients, a NOM-S device was implanted in 22, showing an efficacy of 50%. Finally, 9 patients underwent ECP of the ipsilateral lower-posterior hypothalamus with an efficacy of 88.8%. No serious complications were found following any of these 3 procedures. CONCLUSIONS: The sequential application of these three surgical procedures succeeded in reversing the serious situation of chronic CR refractory to an episodic CR in 93% of patients with acceptable surgical morbidity.

Benito's neuralgia: the first description of the occipital neuralgia was made for Spanish doctors at the beginning of the nineteenth century.

BACKGROUND: The occipital neuralgia affects 3 out of every 100,000 people and includes the neuralgia of the greater occipital nerve (GON) and the neuralgia of the minor and third occipital nerves. These nerves emerge from the posterior branches of the first cervical roots, innervate the muscles of the nape, and provide the sensitivity of the scalp. The most frequent issue is not to find causes that justify neuralgia for what is usually idiopathic. The nerve that most often causes neuralgia is the GON that is usually wrongly called Arnold's nerve, so neuralgia is also called Arnold's neuralgia. METHODS: We have reviewed the first description of occipital neuralgia. RESULTS: Two Spanish doctors, José Benito Lentijo and Mateo Martínez Ramos, had already described in detail the neuralgia of the GON before Arnold was born. The first clinical case of occipital neuralgia due to GON involvement was published by them in a Spanish medical journal in 1821, and they called it cervico-suboccipital neuralgia. CONCLUSION: We claim in this article the role of these two Spanish doctors in the history of Neurology.

[Changes introduced into the recent International Classification of Headache Disorders: ICHD-III beta classification]. / Novedades en la reciente Clasificacion Internacional de las Cefaleas: clasificacion ICHD-III beta.

INTRODUCTION: The International Headache Society (IHS) has published the third edition of the International Classification of Headache Disorders (ICHD-III beta), the most commonly used guide to diagnosing headaches in the world. AIMS: To review the recent additions to the guide, to explain the new entities that appear in it and to compare the conditions that have had their criteria further clarified against the criteria in the previous edition. DEVELOPMENT: We have recorded a large number of clarifications in the criteria in practically all the headaches and neuralgias in the classification, but the conditions that have undergone the most significant clarifications are chronic migraine, primary headache associated with sexual activity, short-lasting unilateral neuralgiform headache attacks, new daily persistent headache, medication-overuse headache, syndrome of transient headache and neurological deficits with cerebrospinal fluid lymphocytosis. The most notable new entities that have been incorporated are external-compression headache, cold-stimulus headache, nummular headache, headache attributed to aeroplane travel and headache attributed to autonomic dysreflexia. Another point to be highlighted is the case of the new headaches (still not considered entities in their own right) included in the appendix, some of the most noteworthy being epicrania fugax, vestibular migraine and infantile colic. CONCLUSIONS: The IHS recommends no longer using the previous classification and changing over to the new classification (ICHD-III beta) in healthcare, teaching and research, in addition to making this new guide as widely known as possible.

TITLE: Novedades en la reciente Clasificacion Internacional de las Cefaleas: clasificacion ICHD-III beta.Introduccion. La Sociedad Internacional de Cefaleas (IHS) ha publicado la tercera edicion de la Clasificacion Internacional de las Cefaleas (ICHD-III beta), la guia diagnostica de las cefaleas mas utilizada en el mundo. Objetivo. Revisar las recientes aportaciones de la guia, explicando las nuevas entidades que en ella aparecen y comparando las entidades que han matizado sus criterios con sus criterios de la edicion precedente. Desarrollo. Hemos registrado multitud de matices en los criterios de practicamente todas las cefaleas y neuralgias de la clasificacion, pero las entidades que han experimentado mas matizaciones trascendentales son la migraña cronica, la cefalea asociada exclusivamente a la actividad sexual, las cefaleas neuralgiformes unilaterales de breve duracion, la cefalea diaria persistente de novo, la cefalea por abuso de medicacion sintomatica, el sindrome de cefalea y deficits neurologicos transitorios con pleocitosis linfocitaria. Las entidades nuevas mas destacables que se han incorporado son las cefaleas por presion externa, las cefaleas por crioestimulo, la cefalea numular, la cefalea atribuida a vuelos de avion y la cefalea atribuida a disreflexia autonomica. Tambien cabe destacar las nuevas cefaleas, aun no consideradas como entidades, que se incorporan al apendice, entre las que destacan la epicranea fugax, la migraña vestibular y los colicos infantiles. Conclusiones. La IHS recomienda utilizar ya la nueva clasificacion (ICHD-III beta), prescindiendo de la anterior clasificacion, en la asistencia, la docencia y la investigacion, asi como hacer la maxima difusion de esta nueva guia.

Migraine attack treatment : a tailor-made suit, not one size fits all.

About 15% of people in the world suffer migraine attacks. Migraine can induce a great impact in the quality of life, and the costs of medical care and loss of productivity can be also high. Non-steroidal anti-inflammatory drugs (NSAIDs) are the best treatment in mild-to-moderate migraine attacks and triptans are the first line option in the acute treatment of moderate-to-severe migraine attacks. At present, there are seven marketed triptans: sumatriptan, rizatriptan, zolmitriptan, eletriptan, naratriptan, almotriptan and frovatriptan. Obviously, every drug presents different pharmacokinetic and pharmacodynamics properties and, moreover, some triptans have several formulations. The prescription of one of these seven triptans for a specified patient is based in the drug profile: efficacy, safety, pharmacokinetics and pharmacodynamics. Other data to take account in the final prescription are clinical characteristics of the migraine attack (speed of onset, intensity of pain, lasting of the attack) and patient characteristics as working habits, life style or medical history. It is therefore mandatory to perform an individualization of the treatment of migraine attack. In recent years, several new patents of drugs have been registered in the treatment of migraine attack, although most of these are already known drugs that only provide new routes of administration. We present an update on the treatment of the migraine attack.

Treatment of chronic migraine with intramuscular pericranial injections of onabotulinumtoxin a.

Chronic migraine is the most frequent and disabling complication of migraine. To date, only two drugs have been specifically analysed for the treatment of chronic migraine, topiramate and onabotulinumtoxin A, and in the evidence-based medicine categories, they have achieved level of evidence I and as such, a grade of recommendation A according to current guidelines. Following the PREEMPT paradigm, pericranial intramuscular onabotulinumtoxin A injections show a good efficacy and safety in chronic migraine patients, both in phase III randomized clinical trials and in a pooled data analyses. Onabotulinumtoxin A injections reduce the number of days of headache and migraine, they reduce the consumption of triptans and disability, and improve the quality of life of migraine patients. For these reasons, onabotulinumtoxin type A is an option as valid as topiramate for the treatment of chronic migraine.

Brain apparent water diffusion coefficient magnetic resonance image during a prolonged visual aura.

BACKGROUND: Reversible changes in brain magnetic resonance imaging (MRI) weighted in diffusion-weighted images (DWI) and apparent water diffusion coefficient (ADC) maps have been reported in acute stroke, epilepsy, eclampsia, and hypoglycemia, but they are contradictory regarding to migraine aura. OBJECTIVE: A 41-year-old woman with known basilar migraine for 5 years consulted about a persistent visual aura (visual snow phenomenon) plus bilateral paresthesias in the extremities for 4 days. The headache was treated with success with 10 mg of wafer rizatriptan and 600 mg of ibuprophen. METHODS: The neurologic and ophthalmologic examination were normal. An urgent brain MRI detected no lesions in T1, T2, fluid-attenuated inversion recovery, and DWI, but an abnormal signal appeared in the left occipital lobe in ADC and (r)ADC maps. The brain MRI angiography, carotid ultrasound study, transesophageal echocardiography, 24-hour cardiac Holter monitoring, and thrombophilia study were normal. RESULTS: A new brain MRI 8 days after did not show any previous lesion in the same sequences. CONCLUSIONS: We present a patient with migraine and transitory abnormal signals in the ADC map of an occipital region during persistent visual aura. The clinical-radiological relationship is congruent. Some similar cases have showed these MRI signals during the aura, suggesting cytotoxic edema, without ischemic lesions in the MRI controls. Theses ADC images probably appear in complex auras.

Mutations in the NKX2-5 gene in patients with stroke and patent foramen ovale.

OBJECTIVE: Patent foramen ovale (PFO) has been related to stroke but its existence has not been explained to date. NKX2-5 is the most implicated gene in fetal atrial septation. We studied NKX2-5 with respect to the presence or absence of PFO in stroke patients. METHODS: A prospective analysis of NKX2-5 regarding age, gender, PFO, right-to-left shunt (RLS) size and atrial septal aneurysm (ASA) was performed in consecutive stroke patients and in 50 controls. The entire coding region and intron-exon boundaries of NKX2-5 gene were analyzed by PCR and sequencing of DNA from peripheral lymphocytes. RESULTS: One hundred patients participated in the study (mean age 56.5+/-12.4 years, 58% males) and PFO was diagnosed in 34% of them by transesophageal echocardiography. RLS was small (12%), moderate (2%) and large (20%). ASA was present in four patients. DNA revealed a novel c.2357G>A change in one PFO patient with cryptogenic stroke. Furthermore, c.182C>T, a mutation previously described in patients with cardiac defects, was detected in two non-PFO women with cryptogenic stroke. None of these changes were detected in our controls. The c.172A>G polymorphism was found in 21% of controls. It appeared more frequently in ASA patients (p=0.084), in cryptogenic PFO stroke patients (p=0.097) and in patients with known causes of stroke (p=0.037). The c.2850C>A polymorphism was also detected in our series with no differences in PFO, RLS size or ASA. CONCLUSION: Despite the fact that the NKX2-5 could account for the persistence of PFO, mutations of this gene in peripheral blood DNA were barely detected in our study.

Individual triptan selection in migraine attack therapy.

About 6% of men and 18% of women suffer migraine attacks. Migraine can induce a great impact in the quality of life of the patient and the costs of medical care and lost productivity can be also high. There are two therapeutic approaches in the treatment of migraine: preventive therapy and acute treatment of migraine attack. Immediate treatment with selective serotonin [5-HT1B/1T] receptor agonists (so-called triptans) is the first-line option in the acute treatment of moderate-severe migraine attacks. The introduction in early nineties of triptans was a revolution in migraine therapy and evidences about their efficacy are at present irrefutable. At the moment, there are seven marketed molecules: sumatriptan, rizatriptan, zolmitriptan, eletriptan, naratriptan, almotriptan and frovatriptan. Obviously, every molecule has different pharmacokinetic and pharmacodinamic properties and, moreover, some triptans have several formulations: tablets, dissolvable tablets, nasal and injections. The prescription of one of these seven triptans for a specified patient is based in the drug profile: efficacy, safety, pharmacokinetics and pharmacodynamics. Despite there are a lot of published studies using triptans, no clinical trial has analyzed all the molecules at the same time. Other data to take account in the final prescription are clinical characteristics of the migraine attack and patient characteristics: labour aspects, style of life and the patient medical history. We present a state-of-the-art of the triptan selection in treatment of moderate-severe migraine attacks.

Clopidogrel in secondary ischemic stroke prevention.

The results obtained in the CAPRIE study in 1996 led to the introduction of the clopidogrel as a new antiplatelet drug in the secondary prevention of acute myocardial infarct (AMI), ischemic stroke (IS) and symptomatic peripheral artery disease (PAD). Clopidogrel showed a similar efficacy and safety than acetylsalicylic acid (ASA). More recently, the combined use of clopidogrel with ASA has evidenced a better protection than ASA alone in some patients: patients with past history of AMI, angina pectoris, intermittent claudication or PAD, IS or TIA, coronary bypass, and diabetes mellitus, patients on treatment with statins, and patients with symptomatic carotid stenosis >/=50%. We review the reported evidence on the efficacy of clopidogrel in the secondary prevention of ischemic stroke.

Patent foramen ovale and prothrombotic markers in young stroke patients.

Patent foramen ovale (PFO) is more frequent in cryptogenic stroke patients than in the general population. The aim of this study was to determine prothrombotic markers regarding PFO in young cryptogenic stroke patients. We prospectively included consecutive cryptogenic stroke patients younger than 55 years. PFO was diagnosed with simultaneous transcranial Doppler and transesophageal echocardiography. We analyzed the following prothrombotic markers: antiphospholipid antibodies (APS), protein C and protein S deficiencies, factor V Leiden FVG1691A, prothrombin gene mutation PTG20210A and coagulation factor XII mutation FXIIC46T. From June 2005 to July 2006 we studied 39 patients, mean age 44.7 +/- 8.6 years, 48.7% men. PFO was detected in 17 patients (43.6%). We found no differences between PFO and non-PFO patients regarding prothrombotic markers: APS (P = 0.851), protein S deficiency (P = 0.851), protein C deficiency (P = 0.249), FVG1691A (P = 0.202), PTG20210A (P = 0.401) or FXIIC46T (P = 0.966). Female gender was the only variable related to prothrombotic markers, independent of PFO (P = 0.001). The only prothrombotic marker related to PFO size (large PFO) was APS (P = 0.043). Large PFO were also related to deep venous thrombosis (P = 0.040) and atrial septal aneurysm (P = 0.010). PFO patients do not present more prothrombotic markers than non-PFO patients, but APS are more frequent in large PFO.

Electrocardiographic findings in patients with cryptogenic ischemic stroke and patent foramen ovale.

BACKGROUND: A characteristic electrocardiogram (ECG) pattern called crochetage has been described in patients with atrial septal defects. Nevertheless, there are discrepancies regarding its frequency in patients with patent foramen ovale (PFO). OBJECTIVE: We analyzed the ECGs of patients who had cryptogenic stroke to study crochetage and other possible patterns in relation to PFO. METHODS: We prospectively included consecutive patients who have had a cryptogenic stroke and are undergoing a right-to-left shunt (RLS) study with transesophageal echocardiography and simultaneous transcranial Doppler. Two blinded and independent cardiologists analyzed the ECGs for crochetage, defined as a notch near the apex of the R wave in inferior limb leads, P wave abnormalities, and right bundle branch block (RBBB). RESULTS: We studied 104 patients whose mean age was 55.1 +/- 12.7 years; 60.6% were men. PFO was detected in 40.4% of patients. Cardiologists recorded crochetage in 26.2% of patients with PFO and 14.5% of patients without PFO (P = .204) and RBBB in 19% and 8% of patients, respectively (P = .132). P wave abnormalities were also detected in 54.8% of patients with PFO and 35.5% of patients without PFO (P = .070). In patients with PFO, biphasic P waves were more frequent in small RLS (P = .006). Although higher frequencies of crochetage in small RLS and RBBB in moderate RLS were detected, these differences did not reach statistical significance (P = .067 and P = .05, respectively). CONCLUSION: There is no characteristic ECG pattern to identify the patients with cryptogenic stroke.