Guidelines for the treatment of acute ischaemic stroke.

INTRODUCTION: Update of Acute Ischaemic Stroke Treatment Guidelines of the Spanish Neurological Society based on a critical review of the literature. Recommendations are made based on levels of evidence from published data and studies. DEVELOPMENT: Organized systems of care should be implemented to ensure access to the optimal management of all acute stroke patients in stroke units. Standard of care should include treatment of blood pressure (should only be treated if values are over 185/105 mmHg), treatment of hyperglycaemia over 155 mg/dl, and treatment of body temperature with antipyretic drugs if it rises above 37.5 °C. Neurological and systemic complications must be prevented and promptly treated. Decompressive hemicraniectomy should be considered in cases of malignant cerebral oedema. Intravenous thrombolysis with rtPA should be administered within 4.5 hours from symptom onset, except when there are contraindications. Intra-arterial pharmacological thrombolysis can be considered within 6 hours, and mechanical thrombectomy within 8 hours from onset, for anterior circulation strokes, while a wider window of opportunity up to 12-24 hours is feasible for posterior strokes. There is not enough evidence to recommend routine use of the so called neuroprotective drugs. Anticoagulation should be administered to patients with cerebral vein thrombosis. Rehabilitation should be started as early as possible. CONCLUSION: Treatment of acute ischaemic stroke includes management of patients in stroke units. Systemic thrombolysis should be considered within 4.5 hours from symptom onset. Intra-arterial approaches with a wider window of opportunity can be an option in certain cases. Protective and restorative therapies are being investigated.

Clinical management guidelines for subarachnoid haemorrhage. Diagnosis and treatment.

OBJECTIVE: To update the Spanish Society of Neurology's guidelines for subarachnoid haemorrhage diagnosis and treatment. MATERIAL AND METHODS: A review and analysis of the existing literature. Recommendations are given based on the level of evidence for each study reviewed. RESULTS: The most common cause of spontaneous subarachnoid haemorrhage (SAH) is cerebral aneurysm rupture. Its estimated incidence in Spain is 9/100 000 inhabitants/year with a relative frequency of approximately 5% of all strokes. Hypertension and smoking are the main risk factors. Stroke patients require treatment in a specialised centre. Admission to a stroke unit should be considered for SAH patients whose initial clinical condition is good (Grades I or II on the Hunt and Hess scale). We recommend early exclusion of aneurysms from the circulation. The diagnostic study of choice for SAH is brain CT (computed tomography) without contrast. If the test is negative and SAH is still suspected, a lumbar puncture should then be performed. The diagnostic tests recommended in order to determine the source of the haemorrhage are MRI (magnetic resonance imaging) and angiography. Doppler ultrasonography studies are very useful for diagnosing and monitoring vasospasm. Nimodipine is recommended for preventing delayed cerebral ischaemia. Blood pressure treatment and neurovascular intervention may be considered in treating refractory vasospasm. CONCLUSIONS: SAH is a severe and complex disease which must be managed in specialised centres by professionals with ample experience in relevant diagnostic and therapeutic processes.

proMetalloproteinase-10 is associated with brain damage and clinical outcome in acute ischemic stroke.

BACKGROUND: Matrix metalloproteinases (MMPs) mediate tissue injury during stroke but also neurovascular remodeling and we have shown that MMP-10 is involved in atherothrombosis. OBJECTIVE: The purpose of this study was to examine the relationship between proMMP-10 and clinical outcome, assessing inflammatory and proteolytic markers, in patients with acute ischemic stroke. METHODS: We prospectively studied 76 patients with ischemic stroke treated with tPA within the first 3 h from symptom onset, compared with 202 non-tPA-treated ischemic stroke patients and 83 asymptomatic subjects. Stroke severity was assessed with the National Institutes of Health Stroke Scale (NIHSS). Hemorrhagic transformation (HT) and severe brain edema were diagnosed by cranial CT. Good functional outcome was defined as a modified Rankin scale score ≤ 2 at 90 days. Serum levels of MMP-9, proMMP-10, TIMP-1, tumor necrosis factor-α (TNFα), interleukin-6 and cellular fibronectin were measured at admission. The effect of TNFα on endothelial proMMP-10 was assessed in vitro. RESULTS: Serum proMMP-10 concentration in ischemic stroke patients, non-treated or treated with t-PA, which was higher than age-matched healthy subjects (P < 0.0001), was independently associated with higher infarct volume, severe brain edema, neurological deterioration and poor functional outcome at 3 months (all P < 0.05), but not with HT. proMMP-10 levels were also independently and positively associated with circulating levels of TNFα (P < 0.0001), which induced its endothelial expression in vitro, both mRNA and protein. MMP-9, however, was only associated with HT and severe edema (all P < 0.05). CONCLUSIONS: Increased serum proMMP-10 after acute ischemic stroke, associated with TNFα, is a new marker of brain damage and poor outcome.

Brown-sequard syndrome after endovascular embolization of vertebral hemangioma.

STUDY DESIGN: Several causes of Brown-Sequard syndrome have been described. Endovascular embolization can be used to treat symptomatic vertebral hemangiomas. We describe a previously undocumented case of Brown-Sequard syndrome followed by endovascular embolization with microcoils of a vertebral hemangioma. We also provide a clinical-radiological correlation of this finding and review the relevant literature. CASE REPORT: A 39-year-old male was referred to our hospital for endovascular treatment of a right T9 hemivertebral hemangioma with compromise of the spinal canal. Fifteen minutes after the procedure, the patient developed right lower limb weakness and numbness on the left leg. The emergency magnetic resonance imaging (MRI) of the spine showed no abnormalities. Five days later, a new spinal MRI revealed an infarction in the right half of the spinal cord at T6 and T7 level. This stroke was probably caused by a microcoil ended up in the right sulcocommisural artery. One week after surgery, the patient was able to raise the right leg against gravity, but sensory deficit showed no improvement. CONCLUSIONS: To the best of our knowledge this is the first case of a Brown-Sequard syndrome related to vertebral hemangioma embolization, a relatively safe technique with no important complications made known until this report. Clinicians should always weight the benefits with the potential devastating complications of this therapeutic option.

Guidelines for the preventive treatment of ischaemic stroke and TIA (I). Update on risk factors and life style.

OBJECTIVE: To update the ad hoc Committee of the Cerebrovascular Diseases Study Group of The Spanish Neurological Society guidelines on prevention of ischaemic stroke (IS) and transient ischaemic attack (TIA). METHODS: We reviewed available evidence on risk factors and means of modifying them to prevent ischaemic stroke and TIA. Levels of evidence and recommendation grades are based on the classification of the Centre for Evidence-Based Medicine. RESULTS: This first section summarises the recommendations for action on the following factors: blood pressure, diabetes, lipids, tobacco and alcohol consumption, diet and physical activity, cardio-embolic diseases, asymptomatic carotid stenosis, hormone replacement therapy and contraceptives, hyperhomocysteinemia, prothrombotic states and sleep apnea syndrome. CONCLUSIONS: Changes in lifestyle and pharmacological treatment for hypertension, diabetes mellitus and dyslipidemia, according to criteria of primary and secondary prevention, are recommended for preventing ischemic stroke.

[Neuro-rehabilitation after stroke]. / Neurorrehabilitación tras el ictus.

INTRODUCTION: the high incidence of stroke results in significant mortality and disability leading to immense health care costs. These costs lead to socioeconomic, budgetary, and staffing repercussions in developing countries. Improvements in stroke management focus mainly on acute neurological treatment, admission to stroke units, fibrinolytic treatment for ischaemic strokes and rehabilitation processes. Among these, rehabilitation has the longest therapeutic window, can be applied in both ischaemic and haemorrhagic strokes, and can improve functional outcomes months after stroke. DEVELOPMENT: Neurologists, because of their knowledge in neuroanatomy, physiopathology, neuro-pharmacology, and brain plasticity, are in an ideal position to actively participate in the neurorehabilitation process. Several processes have been shown to play a role in determining the efficacy of rehabilitation; time from stroke onset to rehabilitation admission and the duration and intensity of treatment. CONCLUSIONS: neurorehabilitation is a sub-speciality in which neurologists should be incorporated into multidisciplinary neurorehabilitation teams. Early time to rehabilitation admission and greater intensity and duration of treatment are associated with better functional outcomes, lower mortality/institutionalisation, and shorter length of stay. In order to be efficient, a concerted effort must be made to ensure patients receive neurorehabilitation treatment in a timely manner with appropriate intensity to maximize patient outcomes during both inpatient and outpatient rehabilitation.

Dietary fibre intake is inversely associated with carotid intima-media thickness: a cross-sectional assessment in the PREDIMED study.

OBJECTIVE: To assess the association between the intake of dietary fibre and carotid intima-media thickness (IMT) in a Mediterranean population at high cardiovascular risk. METHODS: Baseline cross-sectional assessment of 457 men and women (average age 67 years) from two different Spanish centres of the PREDIMED trial. A previously validated food frequency questionnaire (137 food items) was administered by trained dieticians in a face-to-face interview. Mean common carotid IMT was measured using B-mode ultrasound imaging of the right and left carotid arteries by four certified sonographers who used a common protocol. Anthropometric and blood pressure measurements were performed and samples of fasting blood were obtained. Participants were categorized into four groups (roughly quartiles: < or =21; >21 to < or =25; >25 to < or =31 and >31 g/day) of energy-adjusted intake of dietary fibre. Multiple linear regression models were used to adjust for age, sex, centre, smoking, body mass index, diabetes, blood pressure, lipid levels and statin use. RESULTS: In the crude analyses, energy-adjusted fibre intake showed a significant inverse correlation with IMT (r=-0.27, P<0.001). In multivariate analyses, a modest, though statistically significant (P=0.03) inverse association between energy-adjusted fibre intake and IMT was also found. The multivariate-adjusted difference in average IMT was -0.051 mm (95% confidence interval: -0.094 to-0.009, P=0.02) for participants whose intake was >35 g/day, (n=47) when compared with those whose intake was <25 g/day (n=224). CONCLUSIONS: Our results suggest that high fibre intake is inversely associated with carotid atherosclerosis.

Inflammation markers and prediction of post-stroke vascular disease recurrence: the MITICO study.

OBJECTIVE: Vascular disease recurrence following stroke is the main cause of morbidity and mortality. The MITICO study was designed to assess the prognostic value of markers of inflammation in relation to the risk of recurrence of vascular disease. PATIENTS AND METHODS: Multi-centered prospective observational study, in patients with ischemic stroke not receiving anti-coagulation therapy and who were recruited within 1-3 months from stroke onset. Blood samples were obtained at baseline and follow- up for the determination of high-sensitive C reactive protein (CRP), IL-6, IL-10, ICAM-1, VCAM- 1, MMP-9 and cellular fibronectin. Four follow-up visits within the first year were to rule out recurrence. RESULTS: Of 965 patients from 65 hospitals, 780 (aged 67.5+/-11.2 years, 33.6 % female) were valid for main analysis. One-hundred and three patients (13.2 %) had a new adverse vascular event and 116 patients (14.9 %) a vascular event or vascular death (66.4 % stroke, 21.5 % coronary and 12.1 % peripheral). Levels of IL-6 > 5 pg/mL and VCAM-1 > 1350 ng/mL (ROC curve analyses) were associated with vascular disease recurrence risk (OR: 28.7; 95 % CI: 14.2-58.0 vs. OR: 4.1; 95 % CI: 2.4-7.1, respectively) following adjustment for confounding variables. Risk of adverse vascular event or death from vascular disease were associated with IL-6 (OR: 21.2; 95 % CI: 11.6-38.7) and VCAM-1 (OR: 3.8; 95 % CI: 2.3-6.4). CONCLUSIONS: Baseline values of IL-6 > 5 pg/mL and VCAM-1 > 1350 ng/mL increase 21-fold and 4-fold, respectively, the risk of new vascular disease event or death from vascular disease in patients with ischemic stroke not receiving anti-coagulation treatment.

Risk of ischemic stroke and lifetime estrogen exposure.

BACKGROUND: Estrogen loss has been related to higher incidence of stroke in postmenopausal women, but randomized trials have demonstrated an increased risk of stroke in women receiving hormone replacement therapy (HRT). OBJECTIVE: To assess the relationship between exposure to endogenous ovarian hormones and the risk of noncardioembolic ischemic stroke. METHODS: We conducted a multicenter, age-matched, case-control study in postmenopausal women (case: nonembolic ischemic stroke; control: no stroke) comparing duration of ovarian activity or lifetime estrogen exposure, which was defined as age at menarche to age at menopause. Embolic cardiopathy and unreliable gynecologic data were exclusion criteria. Cardiovascular disease risk factors were recorded. The relationships of the principal variables to the risk of stroke were assessed using a conditional logistic regression analysis. RESULTS: There were 430 cases and 905 controls in the study. In the multivariate analysis, hypertension (odds ratio [OR]: 2.73; 95% CI: 2.09 to 3.58; p < 0.0001), diabetes (OR: 3.38; 95% CI: 2.53 to 4.52; p < 0.0001), hyperlipidemia (OR: 1.31; 95% CI: 1.01 to 1.7; p = 0.045), lifespan of ovarian activity <34 years (OR: 1.51; 95% CI: 1.13 to 2.03; p = 0.005), and menarche at <13 years of age (OR 1.49; 95% CI: 1.15 to 1.92; p = 0.002) were independently related to an increased risk of stroke. Obesity (OR: 0.73; 95% CI: 0.56 to 0.95; p = 0.021) was related to a lower risk of stroke. CONCLUSIONS: Longer lifetime exposure to ovarian estrogens may protect against noncardioembolic ischemic stroke. However, a very early age of exposure onset could be disadvantageous.

Prothrombin fragment 1+2 is associated with carotid intima-media thickness in subjects free of clinical cardiovascular disease.

BACKGROUND AND PURPOSE: Thrombin, a central enzyme in the clotting cascade, plays a role not only in thrombosis but also in the progression of atherosclerosis. We studied the relationship between prothrombin fragment 1+2 (F1+2), a specific marker of thrombin generation in vivo, and carotid intima-media thickness (IMT), an index of subclinical atherosclerosis. METHODS: We examined 181 asymptomatic middle-aged subjects (mean age 55.6 years, 76.7% men) free of overt clinical atherosclerotic disease. F1+2 was measured by enzyme-linked immunosorbent assay and IMT by duplex ultrasonography of carotid artery. Multiple linear regression analysis was used to assess the relationship between the 2 parameters. RESULTS: Compared with individuals in the lowest tertile of F1+2, those in the upper tertile (>0.55 nmol/L) showed significantly higher IMT (P<0.01). In correlation analysis, a positive relationship was found between plasma F1+2 and carotid IMT. F1+2 also correlated positively with cholesterol (P<0.008) and low-density lipoprotein cholesterol (P<0.005), but not with blood pressure or body mass index. In the multivariate analysis, the association of F1+2 with carotid IMT remained significant (P<0.001) after adjustment for age, sex, body mass index, systolic blood pressure, cholesterol, diabetes, and smoking. CONCLUSIONS: In a population sample of adults without clinically overt atherosclerotic disease, the plasma levels of F1+2 were significantly associated with carotid IMT, suggesting a relationship between thrombin generation and the development atherosclerosis.

[Systemic autoimmune diseases with neurocutaneous alterations]. / Enfermedades autoinmunes sistémicas con afectación cutaneoneural.

Autoimmune diseases depend on the pathologic activation of cellular clones, potentially harmful, against soft tissues. They can be classified into systemic and organ-specific diseases. In the systemic subtype, in which the abnormal hyperactivity is not as specific, the most remarkable component of the clinical syndrome is frequently the presence of neurological and/or cutaneous manifestations. This article reviews the major pathogenic mechanisms involved in the principal systemic autoimmune conditions including connective tissue diseases (rheumatoid arthritis, systemic lupus erythematosus, polimyositis, dermatomyositis, scleroderma, mixed connective tissue disease, Sjögren's syndrome, overlap syndromes) and vasculitic syndromes (nodous polyarteritis, giant cell arteritis. Wegener's granulomatosis. Behçet disease, microscopic polyarteritis, cryoglobulinemia) as well as their clinical manifestations, focused mainly on neurocutaneous characteristics.

Palatal myoclonus and opioid peptides.

We report a patient who presented palatal myoclonus (PM) after anoxic brain damage that was completely abolished by the administration of opioid agonists. This suggests the involvement of peptide systems in the development of PM.