Antibody titers of individuals vaccinated for COVID-19: A systematic review.

An important preventive measure to mitigate the COVID-19 pandemic is vaccine implementation. In creating vaccines, evoking neutralizing antibody (NAb) production is the main objective. This review determines and compares the NAb titers produced by COVID-19 vaccine recipients based on the vaccine type and the manner of administration. This review includes published articles on studies with healthy participants with a minimum age of 18 years, without previous infections, and those who were given Emergency Use License (EUL) vaccines from WHO. Bias assessment was performed using the Cochrane Risk of Bias and the Newcastle- Ottawa Scale. In all the studies, 40.82% of the primary doses were viral vector platforms. For booster doses, 50% were mRNA platforms. Messenger RNA (mRNA) vaccines have higher titers as homologous than as heterologous vaccines. However, inactivated vaccines and viral vector vaccines have lower titers as homologous than as heterologous vaccines. Meanwhile, subunit vaccines lack data for their titers. Based on the antibody titers, homologous mRNA vaccines are more viral-protective than their heterologous counterparts. Heterologous inactivated and viral vector vaccines are more protective than homologous combinations, mainly when mRNA is the other type in those heterologous combinations. This is because mRNA vaccines elicit higher immunogenicity compared to other types.

Calcitonin gene-related peptide in migraine: from pathophysiology to treatment.

INTRODUCTION: It has been observed in recent years that levels of such molecules as calcitonin gene-related peptide (CGRP) and, to a lesser extent, the pituitary adenylate cyclase-activating peptide are elevated during migraine attacks and in chronic migraine, both in the cerebrospinal fluid and in the serum. Pharmacological reduction of these proteins is clinically significant, with an improvement in patients' migraines. It therefore seems logical that one of the main lines of migraine research should be based on the role of CGRP in the pathophysiology of this entity. DEVELOPMENT: The Spanish Society of Neurology's Headache Study Group decided to draft this document in order to address the evidence on such important issues as the role of CGRP in the pathophysiology of migraine and the mechanism of action of monoclonal antibodies and gepants; and to critically analyse the results of different studies and the profile of patients eligible for treatment with monoclonal antibodies, and the impact in terms of pharmacoeconomics. CONCLUSIONS: The clinical development of gepants, which are CGRP antagonists, for the acute treatment of migraine attacks, and CGRP ligand and receptor monoclonal antibodies offer promising results for these patients.

1st Post-European Headache Federation Meeting: a review of the latest developments presented at the 2020 European Headache Federation Congress. / I Reunión Post-European Headache Federation: revisión de las novedades presentadas en el Congreso de la European Headache Federation de 2020.

INTRODUCTION: After the European Headache Federation (EHF) Congress, renowned Spanish neurologists specialised in migraine presented the most significant latest developments in research in this field at the Post-EHF Meeting. DEVELOPMENT: The main data presented concerning the treatment of chronic and episodic migraine were addressed, with attention paid more specifically to those related to preventive treatments and real-life experience in the management of the disease. An important review was carried out of the new therapeutic targets and the possibilities they offer in terms of understanding the pathophysiology of migraine and its treatment. An update was also presented of the latest developments in the treatment of migraine with fremanezumab, a monoclonal antibody recently authorised by the European Medicines Agency. Participants were also given an update on the latest developments in basic research on the pathology, as well as an overview of the symptoms of migraine and COVID-19. Finally, the repercussions of migraine in terms of its burden on the care and economic resources of the health system were addressed, along with its impact on society. CONCLUSIONS: The meeting summarised the content presented at the 14th EHF Congress, which took place in late June/early July 2020.

TITLE: I Reunión Post-European Headache Federation: revisión de las novedades presentadas en el Congreso de la European Headache Federation de 2020.Introducción. Tras la celebración del congreso de la European Headache Federation (EHF), reconocidos neurólogos españoles expertos en el tratamiento de la migraña expusieron en la Reunión Post-EHF las principales novedades presentadas en el congreso y relacionadas con ese ámbito. Desarrollo. Se abordan los principales datos presentados relacionados con el tratamiento de la migraña crónica y episódica; concretamente, los relacionados con los tratamientos preventivos y la experiencia en vida real en el manejo de la enfermedad. Se hizo una importante revisión de las nuevas dianas terapéuticas y las posibilidades que ofrecen en cuanto al conocimiento de la fisiopatología de la migraña y su tratamiento. Asimismo, se hizo una actualización de las novedades presentadas en el tratamiento de la migraña con fremanezumab, anticuerpo monoclonal recientemente autorizado por la Agencia Europea de Medicamentos. Se hizo una actualización de las novedades en investigación básica en la patología, así como una relación de los síntomas de migraña y COVID-19. Finalmente, se abordaron las implicaciones de la migraña en la carga sanitaria asistencial y económica, y su impacto en la sociedad. Conclusiones. En la reunión se hizo un resumen del contenido presentado en el 14 Congreso de la EHF, que tuvo lugar a finales de junio y principios de julio de 2020.

Document of revision and updating of medication overuse headache (MOH). / Documento de revisión y actualización de la cefalea por uso excesivo de medicación (CUEM).

INTRODUCTION: Medication overuse headache is a secondary headache in which the regular or frequent use of analgesics can increase the frequency of the episodes, causing the transition from episodic to chronic headache. The prevalence of medication overuse headache is approximately 1-2%, with higher rates among women aged 30-50 years and with comorbid psychiatric disorders such as depression or anxiety, or other chronic pain disorders. It is important to be familiar with the management of this disease. To this end, the Spanish Society of Neurology's Headache Study Group has prepared a consensus document addressing this disorder. DEVELOPMENT: These guidelines were prepared by a group of neurologists specialising in headache after a systematic literature review and provides consensus recommendations on the proper management and treatment of medication overuse headache. The treatment of medication overuse headache is often complex, and is based on 4 fundamental pillars: education and information about the condition, preventive treatment, discontinuation of the drug being overused, and treatment for withdrawal symptoms. Follow-up of patients at risk of recurrence is important. CONCLUSIONS: We hope that this document will be useful in daily clinical practice and that it will update and improve understanding of medication overuse headache management.

Evidence of and experience with the use of onabotulinumtoxinA in trigeminal neuralgia and primary headaches other than chronic migraine. / Evidencia y experiencia del uso de onabotulinumtoxinA en neuralgia del trigémino y cefaleas primarias distintas de la migraña crónica.

INTRODUCTION: In the field of headaches, onabotulinumtoxinA (onabotA) is well established as a treatment for chronic migraine (CM). In recent years, it has been used increasingly to treat other primary headaches (high-frequency episodic migraine, trigeminal-autonomic cephalalgias, nummular headache) and trigeminal neuralgia. As this treatment will progressively be incorporated in the management of these patients, we consider it necessary to reflect, with a fundamentally practical approach, on the possible indications of onabotA, beyond CM, as well as its administration protocol, which will differ according to the type of headache and/or neuralgia. DEVELOPMENT: This consensus document was drafted based on a thorough review and analysis of the existing literature and our own clinical experience. The aim of the document is to serve as guidelines for professionals administering onabotA treatment. The first part will address onabotA's mechanism of action, and reasons for its use in other types of headache, from a physiopathological and clinical perspective. In the second part, we will review the available evidence and studies published in recent years. We will add an "expert recommendation" based on our own clinical experience, showing the best patient profile for this treatment and the most adequate dose and administration protocol. CONCLUSION: Treatment with onabotA should always be individualised and considered in selected patients who have not responded to conventional therapy.

Calcitonin gene-related peptide in migraine: from pathophysiology to treatment. / CGRP en migraña: de la fisiopatología a la terapéutica.

INTRODUCTION: It has been observed in recent years that levels of such molecules as calcitonin gene-related peptide (CGRP) and, to a lesser extent, the pituitary adenylate cyclase-activating peptide are elevated during migraine attacks and in chronic migraine, both in the cerebrospinal fluid and in the serum. Pharmacological reduction of these proteins is clinically significant, with an improvement in patients' migraines. It therefore seems logical that one of the main lines of migraine research should be based on the role of CGRP in the pathophysiology of this entity. DEVELOPMENT: The Spanish Society of Neurology's Headache Study Group decided to draft this document in order to address the evidence on such important issues as the role of CGRP in the pathophysiology of migraine and the mechanism of action of monoclonal antibodies and gepants; and to critically analyse the results of different studies and the profile of patients eligible for treatment with monoclonal antibodies, and the impact in terms of pharmacoeconomics. CONCLUSIONS: The clinical development of gepants, which are CGRP antagonists, for the acute treatment of migraine attacks, and CGRP ligand and receptor monoclonal antibodies offer promising results for these patients.

Evidence and experience with onabotulinumtoxinA in chronic migraine: Recommendations for daily clinical practice. / Evidencia y experiencia de bótox en migraña crónica: Recomendaciones para la práctica clínica diaria.

OnabotulinumtoxinA has been demonstrated to be effective as a preventive treatment in patients with chronic migraine (CM). Five years after the approval of onabotulinumtoxinA in Spain, the Headache Study Group of the Spanish Society of Neurology considered it worthwhile to gather a group of experts in treating patients with CM in order to draw up, based on current evidence and our own experience, a series of guidelines aimed at facilitating the use of the drug in daily clinical practice. For this purpose, we posed 12 questions that we ask ourselves as doctors, and which we are also asked by our patients. Each author responded to one question, and the document was then reviewed by everyone. We hope that this review will constitute a practical tool to help neurologists treating patients with CM.

OnabotulinumtoxinA in chronic migraine: predictors of response. A prospective multicentre descriptive study.

BACKGROUND AND PURPOSE: OnabotulinumtoxinA is a treatment specifically approved for the prophylaxis of chronic migraine in adults. The aim of this study was to assess the effectiveness of OnabotulinumtoxinA in chronic migraine after 1 year of treatment in a real-life setting and to identify clinical predictors of outcome. METHODS: We designed a prospective multicentre study performed in 13 hospitals in Spain. Patients underwent a complete medical history and examination. They were treated with OnabotulinumtoxinA every 12 weeks for 1 year. Data about outcome, adverse events, abortive medication use, emergency room use and disability were collected at 3 and 12 months. RESULTS: A total of 725 subjects completed the study. At 12 months, 79.3% showed >50% reduction in number of headaches per month and 94.9% reported no adverse events. Unilaterality of pain, fewer days of disability per month and milder headache at baseline were correlated with good outcome. Duration of disease <12 months increased the chances of response to treatment with OnabotulinumtoxinA (odds ratio, 1.470; 95% confidence interval, 1.123-2.174; P = 0.045). CONCLUSIONS: This study confirmed the effectiveness of treatment with OnabotulinumtoxinA after 1 year of treatment. The chances of a good outcome may be increased by starting treatment in the first 12 months after chronic migraine diagnosis.

Chronic periodontitis is associated with lacunar infarct: a case-control study.

BACKGROUND AND PURPOSE: Chronic periodontitis (ChP) and lacunar infarct (LI) are two common diseases amongst the elderly. Although several studies have shown an association between ischaemic stroke and ChP, little is known about the relationship between ChP and LI. The study aims to investigate whether ChP is associated with the presence of lacunar stroke. METHODS: An age- and gender-matched case-control study of 62 cases (subjects diagnosed with LI) and 60 controls is reported. Clinical periodontal measures (probing pocket depth, recession, clinical attachment level, full mouth plaque score and full mouth gingival bleeding on probing score) were assessed, and associated risk factors for periodontitis and lacunar stroke were ascertained by means of a structured questionnaire. RESULTS: Chronic periodontitis showed a strong association with LI after adjusting for common vascular risk factors (odds ratio 4.20; 95% confidence interval 1.81-10.20; P = 0.001). Likewise, severe ChP and LI also tended to be significantly associated, independent of other vascular covariates (odds ratio 3.53; 95% confidence interval 1.07-12.77; P = 0.04). CONCLUSIONS: Chronic periodontitis was independently associated with the presence of LI after adjusting for well-known vascular risk factors for lacunar stroke. Further observational studies are necessary to investigate the pathophysiological mechanisms that can explain this relationship.

[Creation and enhancement of headache units: the view of neurologists and heads of neurology departments]. / Creacion y potenciacion de las unidades de cefalea: vision de los neurologos y jefes de servicio de neurologia.

Headache is the most common reason for visiting in neurology. Almost a third of all patients surveyed in this specialty visit for this reason. The gradual increase in the complexity of the care afforded to patients with headaches requires neurologists to become more specialised and leads to the creation of specialised units where this more complex care can be implemented. The heads of the neurology department are responsible for structuring and coordinating the different care units. This article shows the findings of a survey carried out on a group of heads of neurology departments in order to determine the current state of headache units, that is, their opinion regarding the creation, functioning and development of headache units in Spanish hospitals, and the parameters of their efficacy and effectiveness.

TITLE: Creacion y potenciacion de las unidades de cefalea: vision de los neurologos y jefes de servicio de neurologia.La cefalea constituye el motivo de consulta mas frecuente en neurologia. Casi la tercera parte de pacientes consultados en esta especialidad lo hace por este motivo. El gradual incremento en la complejidad de asistencia a pacientes con cefalea hace necesaria una mayor especializacion por parte de los neurologos y propicia la creacion de unidades especializadas donde desarrollar esta actividad asistencial mas compleja. La estructuracion y coordinacion de las distintas unidades asistenciales corresponde a los jefes de servicio de neurologia. En este articulo se recogen los resultados de una encuesta realizado a un grupo de jefes de servicio de neurologia para conocer el estado actual de las unidades de cefalea: su opinion sobre la creacion, funcion y desarrollo de unidades de cefalea en los hospitales españoles, y los parametros de eficacia y eficiencia de estas.

[Triptans in clinical practice: effectiveness, tolerance and patient's satisfaction with medication (TRIPRACLI study)]. / Los triptanes en la practica clinica: eficacia, tolerancia y satisfaccion del paciente con los farmacos (estudio TRIPRACLI).

INTRODUCTION AND AIMS: This study was aimed determining the effectiveness, tolerance and satisfaction of patients with migraine as regards different triptans, according to the characteristics of their attacks. At the same time it sought to establish a predictive model that can be used to recommend one or another, depending on those characteristics. PATIENTS AND METHODS: Retrospective observation-based study conducted in headache units in a number of different centres. Patients included in the study were those with migraine who used the same triptan to treat their attacks. Data concerning preference, effectiveness, speed and tolerance were analysed. RESULTS: The analysis included 160 patients (88 females), with a mean age of 42.92 years. The most commonly used triptans were eletriptan, almotriptan and rizatriptan. Both patients and doctors reported a high degree of satisfaction (88% and 65%) with the triptan that was used. In the surveys on preference, patients preferred their current triptan to the previous one (83%) or to non-specific drugs. The overall score on a visual analogue scale was above 7 for all the triptans, without any differences from one to another. On analysing the use of a particular triptan depending on the characteristics of the attacks, no statistically significant differences were found. CONCLUSIONS: In this selected group of patients, triptans are a treatment that patients claim to be very satisfied with. Although there are no overall differences in the scores among different triptans, the fact that certain triptans are used more by patients after previous experiences with others suggests that they are more effective. We did not find any parameter that predicts the use of a particular triptan.

Association of growth factors with arterial recanalization and clinical outcome in patients with ischemic stroke treated with tPA.

SUMMARY BACKGROUND: Growth factors (GF) such as vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1) and granulocyte-colony stimulating factor (G-CSF) have been associated with greater efficacy of tissue plasminogen activator (tPA) in experimental studies. OBJECTIVES: To study the association of these GF with arterial recanalization and clinical outcome in patients with acute ischemic stroke treated with tPA. METHODS: We prospectively studied 79 patients with ischemic stroke attributable to MCA occlusion treated with i.v. tPA within the first 3 h from onset of symptoms. Continuous transcranial color-coded sonography (TCCS) was performed during the first 2 h after tPA bolus to assess early MCA recanalization. Hemorrhagic transformation (HT) was classified according to ECASS II definitions. Good functional outcome was defined as a Rankin scale score of 0-2 at 90 days. GF levels were determined by ELISA. RESULTS: Mean serum levels of VEGF, G-CSF and Ang-1 at baseline were significantly higher in patients with early MCA recanalization (n = 30) (all P < 0.0001). In the multivariate analysis, serum levels of VEGF (OR, 1.03), G-CSF (OR, 1.02) and Ang-1 (OR, 1.07) were independently associated with early MCA recanalization (all P < 0.0001). On the other hand, patients with parenchymal hematoma (PH) (n = 20) showed higher levels of Ang-1 (P < 0.0001). Ang-1 (OR, 1.12; P < 0.0001) was independently associated with PH, whereas patients with good outcome (n = 38) had higher levels of G-CSF (P < 0.0001). G-CSF was independently associated with good outcome (OR, 1.12; P = 0.036). CONCLUSIONS: These findings suggest that GF may enhance arterial recanalization in patients with ischemic stroke treated with t-PA, although they might increase the HT.

Association study of the serotoninergic system in migraine in the Spanish population.

In order to evaluate the contribution of 19 serotonin-related genes to the susceptibility to migraine in a Spanish population we performed a case-control association study of 122 single nucleotide polymorphisms (SNPs), selected according to genetic coverage parameters, in 528 migraine patients -308 with migraine without aura (MO) and 220 with migraine with aura (MA)- and 528 sex-matched migraine-free controls. The single-marker analysis identified nominal associations with the migraine phenotype or with the MO or MA subtypes. The multiple-marker analysis revealed risk haplotypes in three genes that remained significantly associated with migraine after correction by permutations. Two-marker risk haplotypes were identified in the HTR2B (rs16827801T-rs10194776G) and MAOA (rs3027400G-rs2072743C) genes conferring susceptibility to MO, and a four-marker haplotype in DDC was specific of MA (rs2329340A-rs11974297C-rs2044859T-rs11761683G). The present study supports the involvement of HTR2B and MAOA genes in the genetic predisposition to MO, while DDC might confer susceptibility to MA. These results suggest a differential involvement of serotonin-related genes in the genetic background of MO and MA.

High serum levels of leptin are associated with post-stroke depression.

BACKGROUND: Depression is a frequent mood disorder that affects around 33% of stroke patients and has been associated with both poorer outcome and increased mortality. Our aim was to test the possible association between inflammatory and neurotrophic molecular markers and the development of post-stroke depression. METHOD: We studied 134 patients with a first episode of ischemic stroke without previous history of depression or speech disorders. We screened for the existence of major depression symptoms in accordance with DSM-IV criteria and a Yesavage Geriatric Depression Scale (GDS) score >11 at discharge and 1 month after stroke. At these times, serum levels of molecular markers of inflammation [interleukin (IL)-1beta, IL-6, intracellular adhesion molecule 1 (ICAM-1), tumor necrosis factor (TNF)-alpha, leptin and high-sensitivity C-reactive protein (hs-CRP)] and neurotrophic factors [brain-derived neurotrophic factor (BDNF)] were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Twenty-five patients (18.7%) were diagnosed as having major depression at discharge. Out of 104 patients who completed the follow-up period, 23 were depressed at 1 month (22.1%). Patients with major depression showed higher serum leptin levels at discharge [43.4 (23.4-60.2) v. 6.4 (3.7-16.8) ng/ml, p<0.001] and at 1 month after stroke [46.2 (34.0-117.7) v. 6.4 (3.4-12.2) ng/ml, p<0.001). Serum levels of leptin >20.7 ng/ml were independently associated with post-stroke depression [odds ratio (OR) 16.4, 95% confidence interval (CI) 5.2-51.5, p<0.0001]. Leptin levels were even higher in the eight patients who developed depression after discharge [114.6 (87.6-120.2) v. 7.2 (3.6-13.6) ng/ml, p<0.0001]. CONCLUSIONS: Serum leptin levels at discharge are found to be associated with post-stroke depression and may predict its development during the next month.

Brachial arterial flow mediated dilation in acute ischemic stroke.

BACKGROUND AND PURPOSE: Brachial arterial flow-mediated dilation (FMD) reflects endothelium-dependent vasodilation function. FMD is diminished in patients with endothelial dysfunction (ED). Our aim was to investigate the relationship between FMD and outcome for patients with acute ischemic stroke. METHODS: We measured FMD in 120 consecutive patients (58.3% male, median age 73 years) with acute ischemic stroke within the first 48 h of onset of the stroke, using high-resolution ultrasonography. FMD was calculated as the relationship between basal diameter of the brachial artery before (d(1)) and after (d(2)) transient vascular occlusion (300 mmHg for 4 min) was measured using a sphygmomanometer (FMD = d(2) - d(1)/d(1) x 100). Poor outcome was defined as modified Rankin Scale at 3 months >2. FMD was categorized according to ROC analysis and we defined ED as FMD < or = 4.5%. RESULTS: Thirty-three patients (27.5%) had ED. Median % FMD was 9.12 (7.48). FMD negatively correlated to stroke severity (P = 0.045). Median FMD was significantly lower [4.5 (2.3, 10.3) vs. 9.4 (5.6, 15.1), P = 0.003] for patients with poor outcome (n = 38). The adjusted odds ratio of poor outcome for FMD < or = 4.5% was 3.03 (95% CI, 1.09-27.3). CONCLUSIONS: Impaired FMD in patients with acute ischemic stroke is associated with poor outcome.

[Preventive treatment of chronic migraine with zonisamide: a study in patients who are refractory or intolerant to topiramate]. / Tratamiento preventivo de la migraña crónica con zonisamida: un estudio en pacientes refractarios o intolerantes a topiramato.

INTRODUCTION: About half of the patients with chronic migraine do not respond or do not tolerate the different migraine preventatives. AIM: To analyse the efficacy and tolerability of zonisamide in the treatment of migraine in patients who had not responded or tolerated topiramate, the current drug of choice for the treatment of this condition. PATIENTS AND METHODS: Those patients with no response or intolerance to topiramate received zonisamide. This drug was increased 25 mg per week up to a maximum of 200 mg/day. The efficacy of this drug was evaluated in terms of 'response' (reduction in attack frequency below 50%) at the third month of treatment. RESULTS: Our series comprises a total of 34 patients, most of them middle-aged women. All met chronic migraine criteria. Zonisamide showed efficacy (response) in 19 patients (56%), response being excellent in 6 (18%). Nine patients (26%) did not show response, whereas 6 (18%) did not tolerate the drug. CONCLUSIONS: The results, obtained in patients refractory to other preventatives and particularly to topiramate, suggest that zonisamide can be useful in the prevention of chronic migraine. Of course, controlled clinical trials are necessary to confirm these preliminary results.

[Cognitive impairment associated to leukoaraiosis: its pathophysiology, clinical manifestations and treatment]. / Deterioro cognitivo asociado a la leucoaraiosis: fisiopatología, manifestaciones clínicas y tratamiento.

INTRODUCTION AND DEVELOPMENT: Leukoaraiosis is a radiological term which refers to white matter disturbances observed as a hypodensity in computed tomography and hyperintensity in T2-weighted magnetic resonance image. The most accepted theory to explain the mechanism of production of leukoaraiosis is chronic ischemia, due to a damage in penetrating arteries. It is an entity with increasing interest, since it is associated with the presence of cognitive impairment. Clinical manifestations in relation with cognitive functions range from mild affectation to dementia, affecting the processing speed and executive functions. CONCLUSIONS: It seems that the control of vascular risk factors slow the progression of leukoaraiosis and cognitive impairment, and although there are no really effective treatment, it seems that some drugs, such as acetylcholinesterase inhibitors or NMDA-receptor antagonists, exert a beneficial effect, although slight, in cognitive functions.

[Molecular markers are associated with early computed tomography ischemic changes]. / Marcadores moleculares asociados a signos precoces de isquemia en tomografía computarizada cerebral.

INTRODUCTION: During brain ischemia, neurotoxicity, neuroinflammation and blood-brain barrier (BBB) disruption mechanisms are involved, leading to necrosis, edema and hemorrhagic transformation. Cranial computed tomography (CT) is the most widely used method in the diagnosis of acute stroke, and its early performance may help in the selection of patients for certain treatments. Our objective is to identify molecular markers of neuroexcitotoxicity, neuroinflammation and BBB disruption in the acute phase of stroke that might be associated with early ischemic CT signs. METHODS: 311 patients with ischemic stroke within the first 24 h from symptoms onset were prospectively included. We established tres groups based on the time between symptom onset and hospital arrival: < or = 6 h, between 6 and 12 h and >12 h. Cranial CT was performed at admission to evaluate early ischemic signs according to the Alberta Stroke Program Early CT Score (ASPECTS). Blood samples were taken at admission for the determination of molecular markers of neuroexcitotoxicity (glutamate), neuroinflammation (interleukin [IL]-6) and BBB disruption (metalloproteinase [MMP]-9). RESULTS: Patients with ASPECTS score < or =7 showed a worse early and late prognosis. Glutamate >134.4 microM (OR: 9.7; CI 95%: 4.2-22.5; p<0.001), IL-6>15.5 pg/mL (OR: 4.4; CI 95%: 2.1-9.4; p<0.001) and MMP-9 > 87.2 ng/mL (OR: 18.4; CI 95%: 7.2-47.1; p<0.001) were associated with ASPECTS score < or =7. In the logistic regression model, only glutamate >134.4 microM/l in the first 6 h (OR: 13.2; CI95%: 5.4-31.3; p<0.001), IL-6>15.5 pg/mL from 6 to 12 h (OR: 10.5; CI 95 %: 4.1-26.7; p<0.001) and MMP-9 >87.2 ng/ml after 12 h (OR: 24.2; CI 95%: 4.8- 50.2; p < 0.001) were independently associated with ASPECTS score < or = 7. CONCLUSIONS: The ASPECTS score may be considered as a surrogate marker of early neurological deterioration and final infarct volume, and associated with molecular markers of neuroexcitotoxicity, neuroinflammation and BBB disruption.

Statin treatment withdrawal in ischemic stroke: a controlled randomized study.

BACKGROUND: Pretreatment with statins has been shown to reduce brain injury in cerebral ischemia. In this controlled randomized study, we investigated the influence of statin pretreatment and its withdrawal on the outcome of acute ischemic stroke patients. METHODS: From 215 patients admitted within 24 hours of a hemispheric ischemic stroke, 89 patients on chronic statin treatment were randomly assigned either to statin withdrawal for the first 3 days after admission (n = 46) or to immediately receive atorvastatin 20 mg/day (n = 43). The primary outcome event was death or dependency (modified Rankin Scale [mRS] score > 2) at 3 months. Early neurologic deterioration (END) and infarct volume at days 4 to 7 were secondary outcome variables. In a secondary analysis, outcome variables were compared with the nonrandomized patients without previous statin therapy (n = 126). RESULTS: Patients with statin withdrawal showed a higher frequency of mRS score > 2 at the end of follow-up (60.0% vs 39.0%; p = 0.043), END (65.2% vs 20.9%; p < 0.0001), and greater infarct volume (74 [45, 126] vs 26 [12, 70] mL; p = 0.002) compared with the non-statin-withdrawal group. Statin withdrawal was associated with a 4.66 (1.46 to 14.91)-fold increase in the risk of death or dependency, a 8.67 (3.05 to 24.63)-fold increase in the risk of END, and an increase in mean infarct volume of 37.63 mL (SE 10.01; p < 0.001) after adjusting for age and baseline stroke severity. Compared with patients without previous treatment with statins, statin withdrawal was associated with a 19.01 (1.96 to 184.09)-fold increase in the risk of END and an increase in mean infarct volume of 43.51 mL (SE 21.91; p = 0.048). CONCLUSION: Statin withdrawal is associated with increased risk of death or dependency at 90 days. Hence, this treatment should be continued in the acute phase of ischemic stroke.