Tendencies in cerebral aneurism treatment: Analysis of a hospital series. / Tendencias en el tratamiento de los aneurismas cerebrales: análisis de una serie hospitalaria.

INTRODUCTION AND OBJECTIVE: To discover if there have been changes in the treatment time for SAH in our hospital environment. MATERIAL AND METHODS: Comparative analysis of 571 patients treated at Hospital Universitari la Fe during 2 different time periods. The SAH-OLD group consisted of 462 patients attended consecutively between April 1997 and March 2005, while SAH-NEW comprised 109 patients attended consecutively between March 2007 and April 2010. We analysed demographic factors, risk factors, severity at time of admission, time to arteriography, diagnosis of aneurysm, use of surgical or endovascular treatment and time to treatment, frequency of neurological complications, in-hospital deaths, and modified Rankin Scale (mRS) at discharge. RESULTS: Mean time to arteriography was 2.18 ± 2.5 days for the SAH-OLD group and 2.37 ± 2.23 days, for the SAH-NEW group (P=.49). Mortality rates for SAH-OLD patients were calculated at 30%, compared to 18.3% in SAH-NEW patients (P=.01). Among patients surviving the hospital stay in the SAH-OLD group, 13.3% had an mRS > 3, compared to 21.3% of survivors in the SAH-NEW group (P=.06). Two hundred forty-five patients in the SAH-OLD group had cerebral aneurysms and 208 were treated (45% of the patient total). Sixty-five of the SAH-NEW patients received treatment (60% of the patient total, P=.007). In the SAH-OLD group, 62.9% of the patients underwent embolisation vs 74.6% in the SAH-NEW group (P=.08). Time to embolisation was 4.7 ± 8.2 days for SAH-OLD patients and 2.12 ± 2.2 days for SAH-NEW patients (P=.01). Twenty-two percent of SAH-OLD patients underwent surgery, compared to 25.4% in the SAH-NEW group (P=.62). CONCLUSIONS: Care for SAH patients has improved in this hospital: results include fewer mortalities, a higher number of treatments with a smaller proportion of endovascular treatments, and shorter times to treatment. Elapsed time to arteriography remains stable.

Reperfusion therapy in acute ischaemic stroke due to cervical and cerebral artery dissection: Results from a Spanish multicentre study.

INTRODUCTION: Ischaemic stroke (IS) due to cervical and cerebral artery dissection (CAD) is a rare entity, and few data are available on the use of such reperfusion therapies as intravenous fibrinolysis and mechanical thrombectomy in these patients. We analysed the use of these treatments in patients with IS due to CAD and compared them against patients receiving reperfusion treatment for IS of other aetiologies. METHODS: We conducted an observational, retrospective, multicentre study of patients with IS due to CAD recorded in the National Stroke Registry of the Spanish Society of Neurology during the period 2011-2019. Comparative analyses were performed between: a) patients with CAD treated and not treated with reperfusion therapies and b) patients treated with reperfusion for IS due to CAD and patients treated with reperfusion for IS due to other causes. Epidemiological data, stroke variables, and outcomes at discharge and at 3 months were included in the analysis. RESULTS: The study included 21,037 patients with IS: 223 (1%) had IS due to CAD, of whom 68 (30%) received reperfusion treatment. Reperfusion treatments were used less frequently in cases of vertebral artery dissection and more frequently in patients with carotid artery occlusion. Compared to patients with IS due to other causes, patients with CAD were younger, more frequently underwent mechanical thrombectomy, and less frequently received intravenous fibrinolysis. Rates of haemorrhagic complications, mortality, and independence at 3 months were similar in both groups. CONCLUSIONS: Reperfusion therapy is frequently used in patients with IS due to CAD. The outcomes of these patients demonstrate the efficacy and safety of reperfusion treatments, and are comparable to the outcomes of patients with IS due to other aetiologies.

Proprotein convertase subtilisin/kexin type 9 inhibitors in secondary prevention of vascular events in patients with stroke: Consensus document and practice guidance.

INTRODUCTION: Patients with history of stroke or transient ischaemic attack present considerable risk of future vascular events. Reducing levels of low-density lipoprotein (LDL) cholesterol decreases the incidence of new vascular events, although in a substantial number of patients, the currently available lipid-lowering therapies fail to achieve the therapeutic goals recommended in clinical guidelines. The aim of this consensus statement is to provide updated information on the role of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors alirocumab and evolocumab in the secondary prevention of vascular events in patients with history of ischaemic stroke. METHODS: A literature review was performed to identify the main evidence on the use of PCSK9 inhibitors in these patients and the recommended therapeutic targets of LDL cholesterol. The results were discussed in 2 consensus meetings that constituted the basis for the drafting of the document. CONCLUSIONS: PCSK9 inhibitors are effective in reducing vascular risk in secondary prevention; evolocumab specifically has achieved this reduction in patients with history of ischaemic stroke. Moreover, both alirocumab and evolocumab present good safety profiles, even in patients achieving LDL cholesterol levels < 20 mg/dL, and no signs of cognitive impairment have been observed in patients treated with evolocumab who achieved very low levels of LDL cholesterol. In the light of this evidence, we provide practical recommendations about the use of PCSK9 inhibitors in secondary prevention of vascular events in patients with history of ischaemic stroke and follow-up of these patients.

Angioplasty and stenting of symptomatic and asymptomatic vertebral artery stenosis: to treat or not to treat.

BACKGROUND AND PURPOSE: Comprehensive indications for treatment of symptomatic vertebral stenosis remain unavailable. Even less is known about endovascular treatment of asymptomatic cases. We treated symptomatic and asymptomatic vertebral ostium stenosis with angioplasty and stenting and investigated the long term outcome. METHODS: Consecutive patients with two different indications were included. Group 1 (G1) had symptomatic >50% stenosis. Group 2 (G2) had asymptomatic >50% stenosis and severe lesions of anterior circulation and were expected to benefit from additional cerebral blood supply. RESULTS: Twenty nine vertebral origin stenoses in 28 patients (75% men, mean age 64 +/- 9 years) were treated. There were 16 G1 and 13 G2 cases. Technical success rate was 100%. Immediate neurological complications rate was 3.4% (one G1 patient with vertebral TIA due to release of emboli). Two further strokes were seen during follow up (32 +/- 24 months): vertebrobasilar stroke in a G2 patient with permeable stent in V1 segment, new ipsilateral V3 occlusion and high-risk cardioembolic source, and carotid stroke in a G1 patient who had had ipsilateral carotid stenting. There were no deaths of any cause. Asymptomatic restenosis was observed in one out of 19 patients from both groups who underwent a follow up angiography. CONCLUSIONS: Angioplasty and stenting appears to be technically feasible and safe in asymptomatic and symptomatic vertebral stenosis. More studies are needed in order to clarify its role in primary and secondary prevention of vertebrobasilar stroke. High risk anterior circulation lesions should be taken into account as a possible indication in patients with asymptomatic vertebral stenosis.

Stroke and temporal arteritis: A study of 6 cases. / Arteritis temporal e ictus: análisis de 6 casos.

INTRODUCTION: Though uncommon, ischaemic stroke due to temporal arteritis carries serious difficulties for diagnosis and subsequent management and requires a high level of suspicion. METHODS: We analysed a series of 6 patients with biopsy-proven temporal arteritis presenting with ischaemic stroke. We discuss clinical characteristics, difficulties of assessment, short- and long-term progression, treatment, and the usefulness of new diagnostic techniques. RESULTS: Our sample of 6 patients had a mean age of 68.3 years; 50% were women. The majority of patients showed systemic symptoms. Anterior and posterior circulation were affected similarly. MRI angiography, Doppler sonography, and PET-CT proved to be very useful for diagnosis and treatment. Mean follow-up time was 26 months. Clinical outcomes were far from good: 33% scored≥3 on the modified Rankin scale, including one death. Two patients had recurrent stroke despite treatment with full doses of corticosteroids, and 2 underwent angioplasty. CONCLUSIONS: Stroke caused by giant cell arteritis is a serious and potentially severe condition which requires a high level of suspicion and early treatment with corticosteroids. New diagnostic techniques contribute to refining patient assessment and identifying the optimal treatment. Endovascular treatment may be a valid therapeutic option in selected patients.

Proprotein convertase subtilisin/kexin type 9 inhibitors in secondary prevention of vascular events in patients with stroke: Consensus document and practice guidance. / Inhibidores de la proproteína convertasa subtilisina/kexina tipo 9 (iPCSK9) en la prevención secundaria de episodios vasculares en pacientes con ictus isquémico: Documento de consenso y aplicaciones prácticas.

INTRODUCTION: Patients with history of stroke or transient ischaemic attack present considerable risk of future vascular events. Reducing levels of low-density lipoprotein (LDL) cholesterol decreases the incidence of new vascular events, although in a substantial number of patients, the currently available lipid-lowering therapies fail to achieve the therapeutic goals recommended in clinical guidelines. The aim of this consensus statement is to provide updated information on the role of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors alirocumab and evolocumab in the secondary prevention of vascular events in patients with history of ischaemic stroke. METHODS: A literature review was performed to identify the main evidence on the use of PCSK9 inhibitors in these patients and the recommended therapeutic targets of LDL cholesterol. The results were discussed in 2 consensus meetings that constituted the basis for the drafting of the document. CONCLUSIONS: PCSK9 inhibitors are effective in reducing vascular risk in secondary prevention; evolocumab specifically has achieved this reduction in patients with history of ischaemic stroke. Moreover, both alirocumab and evolocumab present good safety profiles, even in patients achieving LDL cholesterol levels <20 mg/dL, and no signs of cognitive impairment have been observed in patients treated with evolocumab who achieved very low levels of LDL cholesterol. In the light of this evidence, we provide practical recommendations about the use of PCSK9 inhibitors in secondary prevention of vascular events in patients with history of ischaemic stroke and follow-up of these patients.

Reperfusion treatment in acute ischaemic stroke due to cervical and cerebral artery dissection: results of a Spanish national multicentre study. / Tratamiento de reperfusión en el ictus isquémico agudo por disección arterial cervicocerebral: descripción de los resultados de un estudio nacional multicéntrico.

INTRODUCTION: Ischaemic stroke (IS) due to cervical and cerebral artery dissection (CAD) is a rare entity, and few data are available on the use of such reperfusion therapies as intravenous fibrinolysis and mechanical thrombectomy in these patients. We analysed the use of these treatments in patients with IS due to CAD and compared them against patients receiving reperfusion treatment for IS of other aetiologies. METHOD: We conducted an observational, retrospective, multicentre study of patients with IS due to CAD recorded in the National Stroke Registry of the Spanish Society of Neurology during the period 2011-2019. Comparative analyses were performed between: a) patients with CAD treated and not treated with reperfusion therapies and b) patients treated with reperfusion for IS due to CAD and patients treated with reperfusion for IS due to other causes. Epidemiological data, stroke variables, and outcomes at discharge and at 3 months were included in the analysis. RESULTS: The study included 21,037 patients with IS: 223 (1%) had IS due to CAD, of whom 68 (30%) received reperfusion treatment. Reperfusion treatments were used less frequently in cases of vertebral artery dissection and more frequently in patients with carotid artery occlusion. Compared to patients with IS due to other causes, patients with CAD were younger, more frequently underwent mechanical thrombectomy, and less frequently received intravenous fibrinolysis. Rates of haemorrhagic complications, mortality, and independence at 3 months were similar in both groups. CONCLUSIONS: Reperfusion therapy is frequently used in patients with IS due to CAD. The outcomes of these patients demonstrate the efficacy and safety of reperfusion treatments, and are comparable to the outcomes of patients with IS due to other aetiologies.

New insights into the pathophysiology of fasciculations in amyotrophic lateral sclerosis: An ultrasound study.

OBJECTIVE: To describe the fasciculation pattern in ALS and to analyse its clinical and pathophysiological significance. METHODS: Ultrasound of 19 muscles was performed in 44 patients with a recent diagnosis (<90 days) of ALS. The number of fasciculations was recorded in each muscle and the muscle thickness and strength were additionally measured in limb muscles. A subgroup of patients were electromyographically assessed. RESULTS: US was performed in 835 muscles and EMG was available in 263 muscles. US detected fasciculations more frequently than EMG. Fasciculations were widespread, especially in upper limbs onset patients and in the cervical region. Fasciculations' number inversely associated with ALSFR-R and body mass index (BMI) and directly with BMI loss and upper motor neuron (UMN) impairment. Our statistical model suggest that fasciculations increase with the initial lower motor neuron (LMN) degeneration, reach their peak when the muscle became mildly to moderately weak, decreasing afterwards with increasing muscle weakness and atrophy. CONCLUSIONS: Our study suggests that both UMN and LMN degeneration trigger fasciculations causing BMI loss. The degree of LMN impairment could account for differences in fasciculations' rates within and between muscles. SIGNIFICANCE: In ALS, fasciculations could explain the link between hyperexcitability and BMI loss.

Inhibidores de la proproteína convertasa subtilisina/kexina tipo 9 (iPCSK9) en la prevención secundaria de episodios vasculares en pacientes con ictus isquémico: Documento de consenso y aplicaciones prácticas / Proprotein convertase subtilisin/kexin type 9 inhibitors in secondary prevention of vascular events in patients with stroke: Consensus document and practice guidance

Introducción: Los pacientes, tras un ictus o un ataque isquémico transitorio, presentan un riesgo muy elevado de sufrir nuevos episodios vasculares. La reducción del nivel de colesterol unido a lipoproteínas de baja densidad (cLDL) reduce la incidencia de nuevos episodios, si bien una proporción importante de pacientes no alcanza los objetivos terapéuticos recomendados con los tratamientos hipolipemiantes actuales. El objetivo de este documento de consenso es actualizar el papel de los inhibidores de la proproteína convertasa subtilisina/kexina tipo 9 (iPCSK9; alirocumab y evolocumab) en la prevención secundaria de episodios vasculares en pacientes con ictus isquémico previo. Métodos: Se realizó una revisión bibliográfica para identificar las principales evidencias sobre el uso de iPCSK9 en estos pacientes y los objetivos terapéuticos recomendados de cLDL. Los resultados se discutieron en 2 reuniones de consenso, que constituyeron la base para la elaboración del documento. Conclusiones: Los iPSCSK9 son eficaces en la reducción del riesgo vascular en prevención secundaria y, específicamente, evolocumab ha demostrado esta reducción en pacientes con ictus isquémico previo. Ambos fármacos han demostrado un buen perfil de seguridad, incluso en pacientes que alcanzaron un nivel de cLDL < 20 mg/dL. En este sentido, en el subestudio de episodios neurocognitivos con evolocumab no se observó ninguna señal de empeoramiento de la función cognitiva en pacientes con nivel muy bajo de cLDL. Con base en estas evidencias, en el documento se presentan recomendaciones prácticas sobre el uso de iPCSK9 para la prevención secundaria y seguimiento de episodios vasculares en pacientes con ictus isquémico previo. (AU)

Introduction: Patients with history of stroke or transient ischaemic attack present considerable risk of future vascular events. Reducing levels of low-density lipoprotein (LDL) cholesterol decreases the incidence of new vascular events, although in a substantial number of patients, the currently available lipid-lowering therapies fail to achieve the therapeutic goals recommended in clinical guidelines. The aim of this consensus statement is to provide updated information on the role of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors alirocumab and evolocumab in the secondary prevention of vascular events in patients with history of ischaemic stroke. Methods: A literature review was performed to identify the main evidence on the use of PCSK9 inhibitors in these patients and the recommended therapeutic targets of LDL cholesterol. The results were discussed in 2 consensus meetings that constituted the basis for the drafting of the document. Conclusions: PCSK9 inhibitors are effective in reducing vascular risk in secondary prevention; evolocumab specifically has achieved this reduction in patients with history of ischaemic stroke. Moreover, both alirocumab and evolocumab present good safety profiles, even in patients achieving LDL cholesterol levels < 20 mg/dL, and no signs of cognitive impairment have been observed in patients treated with evolocumab who achieved very low levels of LDL cholesterol. In the light of this evidence, we provide practical recommendations about the use of PCSK9 inhibitors in secondary prevention of vascular events in patients with history of ischaemic stroke and follow-up of these patients. (AU)

Neurologic complications associated with hepatitis C virus infection.

A series of nine patients with neurologic complications of hepatitis C virus infection is reported. Seven patients presented a combination of chronic sensory polyneuropathy, multineuropathy, and encephalopathy related to cryoglobulinemia. The noncryoglobulinemic symptoms consisted of an anterior optic neuropathy and a restless legs syndrome with small-fiber neuropathy. Corticosteroids and cyclophosphamide were useful in controlling vasculitic episodes. Interferon-alpha caused remission in half of the treated patients.

[Primary intraventricular hemorrhage: an analysis of eight cases]. / Hemorragia intraventricular primaria: análisis de ocho casos.

OBJECTIVE: Primary intraventricular haemorrhage (HIVP) is a rare condition, of diverse aetiology and variable course. We present a series of eight cases of HIVP diagnosed by CT and analyze the different aetiologies. MATERIALS AND METHODS: A retrospective series of 8 cases diagnosed by CT, the risk factors, clinical behaviour, complications and prognosis are evaluated. Neuroimaging findings (CT, MR and/or DIVAS) are described. RESULTS: The most commonly associated factor is arterial hypertension (75%). Clinically, presentation was uniform as evidence of sudden intracranial hypertension with signs of meningeal irritation with little or no neurological focal signs. The commonest complication was hydrocephalus (25%) and the chances of survival in most cases were good. Three causes of bleeding were found: an arteriovenous malformation, an aneurysm and a blood coagulation disorder. Three hypertensive patients with no obvious cause of bleeding had periependimary laguna infarcts. CONCLUSIONS: HIVP is an unusual condition of diverse aetiology, uniform clinical presentation and has a good short term prognosis. We suggest that pathology of the small vessels, induced by hypertension, may play a part in the aetiology of a subgroup of patients with no obvious cause of bleeding.

[Delayed hospitalization of the patient with acute stroke]. / Retraso en la hospitalización del paciente con ictus agudo.

INTRODUCTION AND OBJECTIVE: We analyze the main factors influencing the time delay between onset and admission to the hospital in acute stroke. PATIENTS AND METHODS: Consecutive series of 1,344 patients with acute stroke or transient ischemic attack admitted at two reference hospitals of Valencia and included at the same stroke register. Factors assessed were age, sex, vascular risk factors, stroke onset and arrival at hospital, stroke severity and stroke subtype. RESULTS: In 30% of patients the stroke onset time was unknown. 70.7% of patients with acute stroke, and known onset, arrived to the hospital in the first six hours. The median time from onset to admission was: TIA, 2 hours; cerebral infarct, 3 hours (lacunar infarcts 5 hours, non-lacunar infarcts 2 hours) and intracerebral hemorrhage, 2 hours. Patients with severe stroke arrive earlier at the hospital (p < 0.001). Neither sex, age, nor vascular risk factors influence the delay time. CONCLUSIONS: The arrival time varies with stroke subtype: patients with intracerebral hemorrhage or TIA arrive earlier than those with cerebral infarct, and non-lacunar infarcts earlier than lacunar ones. Furthermore, patients with severe stroke are admitted sooner at the hospital.

[Transitory episode of laughter as the initial symptom of an ischemic stroke]. / Episodio transitorio de risa como síntoma inicial de ictus isquémico.

INTRODUCTION: Pathological laughter occurs in pseudobulbar paralysis, in psychiatric disorders and as a sign of convulsions (gelastic crisis). An extremely rare form is the "fou rire prodromique' a pathological episode of laughter preceding a stroke. The pathogenesis is unknown and classically differentiated from gelastic crises. "Fou rire prodromique' has been described in subcortical ischaemic or haemorrhagic strokes, not in cortical strokes. CLINICAL CASE: We describe a patient with an ischaemic cerebrovascular accident due to embolism of the left Sylvian artery. The clinical picture started with a short episode of pathological laughter which preceded sensitive aphasia and weakness of the right limbs. CONCLUSIONS: We suggest that in the case described it is impossible to differentiate between the "fou rire prodromique' and a gelastic crisis as a first sign of an embolic cerebrovascular accident.

[Lacunar infarct and deep cerebral hemorrhage: a comparison of the risk factors]. / Infarto lacunar y hemorragia cerebral profunda: comparación de factores de riesgo.

INTRODUCTION: Lacunar infarcts (LI) and deep cerebral hemorrhages (DCH) have the same localization and a vasculopathy which appears to be similar, at the level of the small perforating arteries, classically attributed to arterial hypertension (AHT). OBJECTIVES: To compare the vascular risk factors of patients with lacunar ictus (LIc) and those with DCH, to try to determine how these may affect the appearance of one type of stroke or another. PATIENTS AND METHODS: We analyzed a prospective consecutive series of patients with cerebral vascular accidents (CVA), selecting 1,540 patients in the first 1,155 with a first CVA. We recorded demographic data and the following risk factors: previous transient ischemic accident (TIA), AHT, diabetes mellitus (DM), hypercholesterolemia, ischemic cardiopathy, atrial fibrillation and the presence of silent infarcts on CT. RESULTS: Two hundred and four patients had LIc and 163 had DCH. There was a significant dissociation between LIc and a history of TIA, DM, hypercholesterolemia and the presence of silent lacunar-type infarcts on CT. However, after multivariant analysis, DM did not continue to be an independent variable. Arterial blood pressure was found to be greater in the DCH group. CONCLUSIONS: The presence of different risk factors for LIc and DCH may be the key to understanding the mechanism which leads to one type or other of CVA.

[Quality control of Doppler diagnoses in vascular neurology]. / Control de calidad del diagnóstico mediante Doppler en neurología vascular.

INTRODUCTION: The use of ultrasonography in the study of extracranial pathologies is becoming widespread among the different neurology services in our community. Its main limitation is that it is a technique that depends on the explorer. AIMS: The purpose of this study is to determine the reliability of our Neurosonology laboratory by validating its results. PATIENTS AND METHODS: We conducted a retrospective study by selecting the first 100 consecutive patients (with ischemic stroke) who had been examined in the year 2001 in the Neurosonology laboratory in our hospital. These subjects had to fulfil the requirement of having been submitted to both a Doppler study (carotid and transcranial) and a vascular neuroimaging study using magnetic resonance angiography (MRA) or panarteriography of the supra-aortic trunks (SAT) and of the brain by means of femoral puncture. RESULTS: In the study of the SAT the Doppler detected stenosis or occlusion with a sensitivity of 91.4% and a specificity of 92.3% and, therefore, a positive predictive value (PPV) of 86.4%. 75% of the occlusions were diagnosed with three false positives (which were in fact critical stenoses above 95% instead of occlusion). As regards the evaluation of the transcranial Doppler (TCD), the sensitivity of the Doppler scan to detect stenoses above 50% is situated at 79%, with a PPV of 93%. For diffuse atheromatosis, however, sensitivity is 92.8%, and specificity is 93%. DISCUSSION: Findings agree with those offered by other studies conducted in our area using this technique, and show the reliability of this technique carried out in our Neurosonology laboratory. We therefore believe that Doppler echography of the SAT and TCD can be used for achieve an initial evaluation of cerebrovascular pathologies.

[Carotid angioplasty in stenosis following radiotherapy: a review of 12 cases]. / Angioplastia carotidea en estenosis tras radioterapia: revision de 12 casos.

INTRODUCTION: Carotid stenosis is a complication of cervical radiotherapy. In these cases carotid angioplasty has been considered as the elective revascularisation treatment. Yet, the indication to treat is under discussion due to the high rate of restenosis and the scarcity of studies conducted on the long-term development. AIMS: To report on a series of patients with carotid stenosis following radiotherapy who were treated by means of angioplasty, the aim being to analyse their long- and short-term development. PATIENTS AND METHODS: Of a series of 426 patients with carotid stenosis treated by endovascular means, 12 of them (2.8%) had previously received radiotherapy in the neck. All of them were submitted to a clinical and imaging follow-up. Data were collected concerning the rate of complications during the first four weeks and in the long term, as well as the rate of restenosis in the follow-up. RESULTS: The mean interval between radiotherapy and the detection of stenosis was 14.7 years. Ten patients (83.3%) were symptomatic. No complications occurred during the first four weeks following the angioplasty. The mean follow-up time was 45.09 months: 16.7% of patients presented a stroke, 8.3% suffered acute myocardial infarction and 33.3% died (16.6% due to cancer). At least six patients (50%) were diagnosed with restenosis, all equal to or greater than 50% and none of them were symptomatic. CONCLUSIONS: Carotid angioplasty is a safe, effective technique in stenosis following radiotherapy, with few short-term complications. The rate of carotid restenosis is high. The main cause of death is cancer.

Hyperhomocysteinemia, obesity and cryptogenic stroke.

BACKGROUND: The pathogenic role of hyperhomocysteinemia in cryptogenic stroke is not well established. We aimed to determine homocysteine levels in patients with cryptogenic stroke considering the possible variables that may act as confounders and analyze the influence of obesity on this association. PATIENTS AND METHODS: We conducted a case-control study in 123 patients with cryptogenic stroke aged 42 ± 12 years and in 153 control subjects aged 42 ± 13 years. Serum homocysteine was determined by fluorescence polarization immunoassay. RESULTS: Patients showed statistically higher levels of homocysteine, creatinine and higher BMI than controls (p = 0.045, p = 0.014, p = 0.013), respectively. After multivariate adjustment the differences in homocysteine levels disappeared (p = 0.774). When subjects were classified according to the presence or absence of obesity, the differences in the prevalence of hyperhomocysteinemia (homocysteine >15 µM) were highly significant, being higher in patients than in controls (p = 0.009). Likewise, mean values of homocysteine in obese were higher in cases than in controls (16.9 ± 9.5 µM vs. 10.12 ± 2.5 µM; p = 0.020), remaining significant after adjusting for the above mentioned confounders. CONCLUSION: Although in general, hyperhomocysteinemia does not seem to constitute an independent risk factor for cryptogenic stroke, it significantly increases the risk in obese subjects; therefore it is convenient to decrease its levels in this sub-group to minimize the risk.

Residual platelet thromboxane A2 and prothrombotic effects of erythrocytes are important determinants of aspirin resistance in patients with vascular disease.

BACKGROUND: Permanent inactivation of cyclooxygenase-1 and inhibition of platelet thromboxane A(2) (TxA(2)) constitute the main mechanisms underlying the prevention of vascular disease by aspirin. METHODS AND RESULTS: We studied platelet TxA(2) synthesis and its impact on platelet reactivity and platelet-erythrocyte [platelet-rich plasma (PRP)-RBC] interactions in 533 aspirin-treated patients with vascular disease. Seventy aspirin-free and 16 aspirin-treated normal subjects were evaluated as controls. Collagen (1 mug mL(-1))-induced platelet activation ((14)C-5HT release) and recruitment (proaggregatory activity of cell-free releasates from activated platelets) were assessed in PRP, PRP + RBC, and whole blood (WB). TxA(2) was quantified in releasates from WB. Aspirin inhibited TxA(2) synthesis and platelet function in all patients, but to different degrees. Forty-two patients (8%) displayed partial (<95%) inhibition of TxA(2) relative to that of aspirin-free controls. They produced >3.5 ng mL(-1) TxA(2) and had higher platelet reactivity than 491 patients who had undetectable TxA(2) or produced residual TxA(2) (R-TxA(2);