Jose Ignacio Tembl

Migraine, patent foramen ovale and migraine triggers

Little information exists about a causal association between PFO and migraine. Some patients identify Valsalva-provoking activities (VPA) as migraine triggers. Therefore, we speculate about a pathogenic connection. The object of the study is to investigate the prevalence of right-to-left shunt (RLS) in a cohort of patients suffering migraine with aura (MA) and its possible association with migraine attacks triggered by VPA. We investigated the circumstances triggering the migraine attacks, in a consecutive series of 72 MA patients and in a series of migraine without aura age and gender-matched. The presence and extent of RLS was assessed by transcranial Doppler. Massive RLS appeared in 38.9% of MA and in 6.5% of migraine without aura (p<0.001). MA patients identified at least one VPA as headache trigger in 45.8%. A trend was found between these triggering activities and massive RLS, both in MAgroup OR 2.7 [1.02–7.17] and in all migraine patients OR 2.5 [1.01–6.11]. According to our results, patients with migraine who have larger RLS tend to recognize activities that increase the extent of the shunt as a trigger of their migraine attacks.

Postradiosurgery Hemorrhage Rates of Arteriovenous Malformations of the Brain Influencing Factors and Evolution With Time

Background and Purpose— The long-term benefit of radiosurgery of brain arteriovenous malformations (AVM), especially nonhemorrhagic cases, is controversial. We calculated hemorrhage rates pre- and posttreatment and analyzed the risk factors for bleeding based on cases followed at our site. Methods— One hundred eight patients, age 36±17 years, 56 men. The mean follow-up was 65±44 months (median, 54; interquartile range, 33–94). Most AVMs were small (74.1% <3 cm in diameter); 48.1% were located in an eloquent area, 27.8% had deep drainage, and 39.8% presented with hemorrhage. Results— The annual hemorrhage rate for any undiagnosed AVM was 1.2%, and 3.3% for AVMs with hemorrhagic presentation. Older patients, cortical or subcortical AVMs, and cases with multiple draining veins were less likely to present with bleeding. During the first 36 months postradiosurgery, hemorrhagic AVMs had a rebleeding rate of 2.1%, and a rate of 1.1% from 3 years onwards. Nonhemorrhagic AVMs had a hemorrhage rate of 1.4% during the first 3 years and 0.3% afterward. Arterial hypertension and nidus volume were independent predictors of bleeding after treatment. Mean nidus obliteration time was 37±18 months (median, 32; interquartile range, 25–40), with hemorrhage rate of 1.3% before and 0.6% after obliteration, and 1.9% for AVMs that were not closed at the end of follow-up. Conclusions— Both hemorrhagic and nonhemorrhagic AVMs benefit from radiosurgical therapy, with gradual decrease in their bleeding rates over the years. Albeit small, the risk of hemorrhage persists during the entirety of follow-up, being higher for cases with hemorrhagic presentation and nonobliterated AVM.

Circulating MicroRNAs as Novel Biomarkers of Stenosis Progression in Asymptomatic Carotid Stenosis

Background and Purpose— Progression of asymptomatic carotid artery stenosis (ACAS) in patients with >50% luminal narrowing is considered a potential risk factor for ischemic stroke; however, subclinical molecular biomarkers of ACAS progression are lacking. Recent studies suggest a regulatory function for several microRNAs (miRNAs) on the evolution of carotid plaque, but its role in ACAS progression is mostly unknown. The aim of our study was to investigate a wide miRNA panel in peripheral blood exosomes from patients with ACAS to associate circulating miRNA expression profiles with stenosis progression. Methods— The study included 60 patients with ACAS carrying >50% luminal narrowing. First, miRNA expression profiles of circulating exosomes were determined by Affymetrix microarrays from plasma samples of 16 patients from the cohort. Second, those miRNAs among the most differentially expressed in patients with ACAS progression were quantified by real-time polymerase chain reaction in a separate replication cohort of 39 subjects within the patient sample. Results— Our results showed that ACAS progression was associated with development of stroke. MiR-199b-3p, miR-27b-3p, miR-130a-3p, miR-221-3p, and miR-24-3p presented significant higher expression in those patients with ACAS progression. Conclusions— In conclusion, our study supports that specific circulating miRNA expression profiles could provide a new tool that complements the monitoring of ACAS progression, improving therapeutic approaches to prevent ischemic stroke.

Neutrophil extracellular traps are increased in patients with acute ischemic stroke: prognostic significance

Neutrophil extracellular traps (NETs) are networks of DNA, histones, and proteolytic enzymes produced by activated neutrophils through different mechanisms. NET formation is promoted by activated platelets and can in turn activate platelets, thus favoring thrombotic processes. NETs have been detected in venous and arterial thrombosis, but data in stroke are scarce. The aim of this study was to evaluate NETs in the plasma of patients with acute ischemic stroke and their potential association with baseline clinical characteristics, stroke severity, and one-year clinical outcomes. The study included 243 patients with acute ischemic stroke. Clinical and demographic data and scores of stroke severity (NIHSS and mRs) at onset and discharge were recorded. Markers of NETs (cell-free DNA, nucleosomes, and citrullinated histone 3 (citH3)), were determined in plasma. Patients were followed-up for 12 months after the ischemic event. NETs were significantly elevated in the plasma of patients with acute ischemic stroke when compared to healthy subjects. NETs were increased in patients who were over 65 years of age and in those with a history of atrial fibrillation (AF), cardioembolic stroke, high glucose levels, and severe stroke scores at admission and discharge. In multivariate analysis, elevated levels of citH3, the most specific marker of NETs, at onset were independently associated with AF and all-cause mortality at one-year follow-up. NETs play a role in the pathophysiology of stroke and are associated with severity and mortality. In conclusion, citH3 may constitute a useful prognostic marker and therapeutic target in patients with acute stroke.

Embolism and impaired washout: A possible explanation of border zone strokes in hypereosinophilic syndrome

We describe 4 patients with stroke caused by hypereosinophilic syndrome, all of whom presented with border zone infarcts, and discuss the possible underlying mechanism. Cardioembolism (endomiocardial fibrosis) would coexist with impaired washout (perfusion disturbance due to high eosinophil count and/or eosinophil-derived substances), explaining the watershed characteristics of the infarcts.

Influence of COX-inhibiting Analgesics on the Platelet Function of Patients with Subarachnoid Hemorrhage

BACKGROUND Platelet function of patients with subarachnoid hemorrhage (SAH) may play an important part in both rebleeding and delayed cerebral ischemia, but little is known about aggregation pathways during the acute phase of stroke. Analgesics are used regularly in the first days after bleeding, and some can potentially inhibit the cyclooxygenase (COX) enzyme. We examined the platelet function of patients with SAH in order to describe their basal situation and determine whether the administration of intravenous nonsteroidal antiinflammatory drugs (NSAIDs) affected platelet aggregation. METHODS Arachidonic acid (AA)-induced aggregation and the platelet function analyzer (PFA)-100 test with collagen/epinephrine cartridges were used to study a group of SAH patients that was treated with dexketoprofen and dipyrone and to compare them to patients that had received no analgesia. RESULTS Ninety-six consecutive SAH patients prospectively enrolled in platelet studies. Twenty-seven patients were taking NSAIDs (10 on dexketoprofen and 17 on dipyrone), and there were 15 cases in the control group. AA-induced aggregation was 10% ± 3.2% for NSAIDs (mean ± standard error), specifically 17.2% ± 7% for dexketoprofen and 5.7% ± 1% for dipyrone. Aggregation in the control group was 72.4% ± 6% (P = .001). Both analgesics slowed the platelet plug formation during the PFA-100 test, with closure times of 237.2 ± 25 seconds for dexketoprofen and 198.4 ± 22 seconds for dipyrone and 138.1 ± 21 seconds in controls (P = .02). CONCLUSIONS The administration of COX-inhibiting analgesics leads to an hypoaggregability state in the first days of SAH. Further insight into their impact on complications such as rebleeding and delayed cerebral ischemia is needed in order to optimize the headache treatment of SAH.

Adherence to Aspirin in Secondary Prevention of Ischemic Stroke

Objective: Compliance with antiplatelet therapy is essential for the efficiency of secondary prevention of ischemic stroke. The objective of this study was to evaluate adherence to aspirin treatment in patients with ischemic stroke. Patients and Methods: We studied outpatients of 5 neurological ambulatory centers in an urban city, Valencia, all with a history of ischemic stroke who had received aspirin for at least 6 months. A personal interview was carried out in all cases, during which the patients were questioned about adherence to treatment. Platelet thromboxane A2 synthesis was assessed in a single laboratory for the biochemical determination in all patients. Results: A total of 73 patients (mean age 67) were studied, with a mean duration of aspirin therapy of 25.4 months (range 6–144 months). Sixty-six patients (90.4%) were included in laboratory tests. All showed inhibition of thromboxane A2 synthesis, consistent with adherence to treatment. Conclusions: Aspirin compliance was found to be excellent. All the patients who presented themselves for laboratory tests were taking aspirin. Even if the patients who failed to show up for laboratory testing are regarded as noncompliants, at least 90% of all patients were compliants – in agreement with the findings of the recent literature. Personal interview plus biochemical determination of platelet thromboxane A2 synthesis seem adequate for assessing adherence to aspirin.

Mesencephalic area measured by transcranial sonography in the differential diagnosis of parkinsonism

BACKGROUND Transcranial B-mode sonography (TCS) has become an important tool in the differential diagnosis of parkinsonism given that current technology enables an adequate assessment of brain structures. In this study we aimed at evaluating the usefulness of midbrain area measured by TCS in the differential diagnosis between Parkinsons Disease (PD) and Progressive Supranuclear Palsy (PSP). METHODS Patients with a diagnosis of PD or PSP according to current clinical criteria were recruited. PSP patients were classified as Richardsons syndrome and PSP-parkinsonism. TCS was performed and the mesencephalic area and third ventricle width were measured offline by an examiner blinded to clinical diagnosis. RESULTS TCS was performed in 60 patients (75% PD, 25% PSP). Eight patients (13,3%) had inadequate acoustic window. Patients with PSP had a smaller mesencephalic area (3.58 cm(2) vs 5.28 cm(2), p < 0.001). A mesencephalic area ≥4.27 cm(2) discriminates PD from PSP with a positive predictive value 100%. Patients with PSP also had a higher third ventricle diameter (8.84 mm vs 5.11 mm, p < 0.001). Within the PSP group patients with Richardsons syndrome had a wider third ventricle than patients with PSP-Parkinsonism phenotype (9.57 mm vs 7 mm, p = 0.01), but no differences were found in the mesencephalic area between both phenotypes. CONCLUSIONS Measurement of the mesencephalic area and the third ventricle width by TCS is a non-invasive, easily accessible technique that is useful in the differential diagnosis between PD and PSP, at least in the late stages of the disease.

Characterisation of DWI-MRI confirmed cerebral infarcts in patients with subarachnoid haemorrhage and their association with MMP-9 levels

Abstract Objectives: It has been suggested that metalloproteinase-9 (MMP-9) could predict the onset of cerebral vasospasm after subarachnoidal haemorrhage (SAH). The aim of this study was to analyse, in patients with SAH, the difference between patients with MRI ischaemic infarcts and patients without, and to investigate the role of metalloproteases as a prognostic factor for ischaemic infarcts. Methods: Sixty eight consecutive patients with SAH and diffusion-weighted magnetic resonance imaging (DWI-MRI) done 3 weeks after SAH. We define two groups, with and without DWI-MRI infarcts. Blood samples were taken at entry, 3 days and 1 week MMP-9 was determined through ELISA method. Results: Forty per cent were male, with a mean age of 54 ± 14 years. Twenty five patients, 36.8%, had DWI-MRI infarcts; in patients with MRI infarcts, SAH was more severe (Fisher = 4 52 vs 25.6%, P = 0.037), with more morbi-mortality (Rankin>3 48 vs 18.6%, P = 0.014), and more symptomatic vasospasm (28 vs 7%, P = 0.031). Levels of MMP-9 were higher than controls, but there were no significant differences between patients with and without infarcts (first determination no infarcts 39.40 ng/ml ± 35.40 vs infarcts 49.75 ng/ml ± 34.54, P>0.005, 3 days no infarcts 72.10 ng/ml ± 70.95 vs infarcts 62.28 ± 33.84, P>0.005, 1 week no infarcts 148.48 ng/ml ± 142.73 vs infarcts 91.51 ng/ml ± 41.20, P>0.005). Conclusion: Thirty eight percent in a well-studied series of patients with SAH have DWI-MRI infarcts; the infarcts were associated to SAH severity, SAH outcome and symptomatic vasospasm. Metalloproteinase-9 was higher in SAH patients than in controls, but it could not discriminate the infarct patients.

TXA2 synthesis and COX1-independent platelet reactivity in aspirin-treated patients soon after acute cerebral stroke or transient ischaemic attack

INTRODUCTION The pharmacological target of aspirin is the inhibition of cyclooxygenase-1 (COX1) and thromboxane-A2 (TX) synthesis. Very few data are available on TX assessment in patients with stroke. We studied platelet TX synthesis, COX1-independent platelet reactivity, the influence of platelet-erythrocyte interactions and the potential association between platelet responses and the severity of stroke, evaluated with a clinical score (NIHSS). MATERIAL AND METHODS We examined 157 aspirin-treated patients with acute stroke or TIA, 128 aspirin-free and 15 aspirin-treated healthy subjects (HS). Collagen-induced TX, platelet recruitment in whole blood and platelets ± erythrocytes (haematocrit 40%) were assessed in patients on daily-aspirin within three days from onset. Arachidonic-acid-, ADP-, thrombin-receptor activating peptide TRAP-, and collagen-induced aggregation were also evaluated. RESULTS Partial TX inhibition (<95% inhibition vs aspirin-free controls) was observed in 13% of patients. This was associated with marked increases in COX1-dependent responses (arachidonic-acid- and collagen-induced aggregation and platelet recruitment; P<0.0001) but not with differences in ADP- or TRAP-induced aggregation. Partial TX inhibition was independently associated with severe stroke (NIHSS ≥ 12) at both admission (P<0.05) and discharge (P<0.05). Among patients with fully blocked TX, those with elevated COX1-independent platelet reactivity (mean+2SD of aspirin-treated HS) were most likely to suffer severe stroke (P<0.05). Platelet-erythrocyte interactions enhanced platelet reactivity in these patients by COX1-dependent and -independent mechanisms (P<0.0001). CONCLUSIONS TX inhibition by aspirin varied across patients. Partial TX inhibition and COX1-independent platelet hyperfunction were associated with more-severe stroke.