The effect of post-stroke hyperglycaemia on the levels of brain damage and repair-related circulating biomarkers: the Glycaemia in Acute Stroke Study II.

BACKGROUND AND PURPOSE: The aim was to identify whether post-stroke hyperglycaemia (PSH) influences the levels of circulating biomarkers of brain damage and repair, and to explore whether these biomarkers mediate the effect of PSH on the ischaemic stroke (IS) outcome. METHODS: This was a secondary analysis of the Glycaemia in Acute Stroke II study. Biomarkers of inflammation, prothrombotic activity, endothelial dysfunction, blood-brain barrier rupture, cell death and brain repair processes were analysed at 24-48 h (baseline) and 72-96 h (follow-up) after IS. The associations of the biomarkers and stroke outcome (modified Rankin Scale score at 3 months) based on the presence of PSH were compared. RESULTS: A total of 174 patients participated in this sub-study. Brain-derived neurotrophic factor (BDNF) at admission was negatively correlated with glucose levels. PSH was associated with a trend toward higher levels of endothelial progenitor cells (EPCs) at baseline. The EPCs in the PSH group then decreased in the follow-up samples (-8.5 ± 10.3) compared with the non-PSH group (4.7 ± 7.33; P = 0.024). However, neither BDNF nor EPC values had correlation with the 3-month outcome. Higher interleukin-6 at follow-up was associated with poor outcomes (modified Rankin Scale > 2) independently of PSH. CONCLUSION: Post-stroke hyperglycaemia appears to be associated with a negative regulation of BDNF and a different reaction in EPC levels. However, neither BDNF nor EPCs showed significant mediation of the PSH association with IS outcome, and only higher interleukin-6 in the follow-up samples (72-96 h) was related to poor outcomes, independently of PSH status. Further studies are needed to achieve definite conclusions.

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.

[Endovascular treatment in acute ischaemic stroke. A stroke care plan for the region of Madrid]. / Tratamiento endovascular en el ictus isquémico agudo. Plan de Atención al Ictus en la Comunidad de Madrid.

INTRODUCTION: Endovascular therapies (intra-arterial thrombolysis and mechanical thrombectomy) after acute ischaemic stroke are being implemented in the clinical setting even as they are still being researched. Since we lack sufficient data to establish accurate evidence-based recommendations for use of these treatments, we must develop clinical protocols based on current knowledge and carefully monitor all procedures. DEVELOPMENT: After review of the literature and holding work sessions to reach a consensus among experts, we developed a clinical protocol including indications and contraindications for endovascular therapies use in acute ischaemic stroke. The protocol includes methodology recommendations for diagnosing and selecting patients, performing revascularisation procedures, and for subsequent patient management. Its objective is to increase the likelihood of efficacy and treatment benefit and minimise risk of complications and ineffective recanalisation. Based on an analysis of healthcare needs and available resources, a cooperative inter-hospital care system has been developed. This helps to ensure availability of endovascular therapies to all patients, a fast response time, and a good cost-to-efficacy ratio. It includes also a prospective register which serves to monitor procedures in order to identify any opportunities for improvement. CONCLUSIONS: Implementation of endovascular techniques for treating acute ischaemic stroke requires the elaboration of evidence-based clinical protocols and the establishment of appropriate cooperative healthcare networks guaranteeing both the availability and the quality of these actions. Such procedures must be monitored in order to improve methodology.

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.

Utility of the assessment of echogenicity in the identification of symptomatic carotid artery atheroma plaques in ischemic stroke patients.

BACKGROUND AND PURPOSE: Echogenicity of atheroma carotid plaques is related to a higher risk of stroke. Clinical and subjective ultrasound criteria are used to identify symptomatic plaques, but the standardized grayscale median (GSM) value may be an objective tool for this diagnosis. Our aim was to analyze the utility of assessing the echogenicity of atheroma carotid plaques in the identification of symptomatic plaques. METHODS: Observational prospective study with inclusion of acute noncardioembolic anterior cerebral circulation ischemic stroke patients. Only patients with bilateral atheroma plaques were included. Echogenicity of plaques was measured by a digital and standardized grayscale system in carotid ultrasound B-mode (longitudinal projection) conducted within the first week after admission. RESULTS: Sixty-six patients were included and 132 plaques were examined. Symptomatic atheroma plaques were less echogenic than asymptomatic ones (GSM 20.0 vs. 29.0; p = 0.002). A ROC curve analysis showed the predictive value of GSM with an AUC of 0.707 (95% CI 0.592-0.823; p = 0.002) and pointed to a value of 24.4 as the optimal cut-off level to identify a plaque as symptomatic (74% sensitivity; 67% specificity). This GSM cut-off point remained significantly associated with a high probability of symptomatic plaque even after the inclusion of the degree of carotid stenosis (either >70% or >50%) in the multivariate logistic regression models. CONCLUSIONS: The assessment of echogenicity of atheroma carotid plaques by the GSM value combined with clinical characteristics and stenosis degree may be useful in the identification of symptomatic plaques.

Functional recovery after hematic administration of allogenic mesenchymal stem cells in acute ischemic stroke in rats.

Hematic administration of bone marrow-derived mesenchymal stem cells (MSCs) in acute ischemic stroke may not only be an effective reparative treatment but also a brain protective therapy that improves neurological recovery. Our purpose was to study whether either i.v. or intracarotid (i.c.) administration of allogenic MSCs during the acute phase were effective in improving neurological recovery and decreasing brain damage in an experimental rat model. In a model of permanent middle cerebral artery occlusion (pMCAO), we analyzed: neurological evaluation; MSCs migration and implantation; interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels; lesion volume; cell death; cellular proliferation; vascular endothelial growth factor (VEGF) expression and blood vessel number. Regardless of the administration route, treated groups showed better neurological recovery, without significant differences between the two groups. Migration and implantation of MSCs in the lesion area was observed in animals receiving i.c. but not i.v. treatment. The highest cytokine values were observed in the i.v. MSCs and i.c. control groups, and these levels were significantly different from the corresponding i.v. control and i.c. MSCs groups, respectively. In addition, there were significant differences between the i.v. MSCs and i.c. MSCs groups in IL-6 levels. Neither treatment reduced infarction volume. However, cell death, measured as TUNEL+ cells was decreased with significant differences between control groups. BrdU+ cells were also significantly increased in the peri-infarct zone at 14 days. VEGF expression was significantly higher in the i.c. MSCs group than in the i.c. control group and blood vessel number was significantly higher in treated groups than control groups with significant differences in the peri-infarct zone at 14 days. We conclude that allogenic MSCs administration shows therapeutic efficacy in our acute ischemic stroke model. Both routes demonstrably improved neurological recovery and provided brain protection.

[Glatiramer acetate in interferon beta non respondent relapsing-remitting multiple sclerosis]. / Acetato de glatiramero en pacientes con esclerosis múltiple remitente-recurrente no respondedores al interferón beta.

INTRODUCTION AND OBJECTIVE: There are 4 immunomodulator treatments approved as first line therapy for patients with re-lapsing-remitting multiple sclerosis (RRMS). The objective of this study is to assess if glatiramer acetate (GA) is useful or not in patients who have discontinued interferon beta due to a suboptimal response or adverse events. METHODS: This is an observational and retrospective study in RRMS patients who discontinued IFN-beta therapy (2.9+/-2.4 years of treatment) and switched to GA (1.9+/-1.4 years). They were classified in 2 groups depending on the reason for discontinuation: suboptimal response or side effects. In both treatments we analysed number of relapses, treatment duration and causes of discontinuation. RESULTS: We included 58 patients of which 20 discontinued IFN-beta for lack of effectiveness whereas 38 were due to adverse events. Patients who discontinued for suboptimal response changed from 1.38 +/- 0.95 relapses per year with IFN-beta to 0.52+/-0.86 with GA. Patients who discontinued for adverse events changed from 0.33 +/- 0.64 relapses per year with IFN-beta to 0.37+/-0.79 with GA. CONCLUSIONS: GA can be considered a good alternative treatment for MS patients with a suboptimal response or adverse events with IFN-beta which confirms the existence of different mechanisms of action in both drugs.

Stroke due to septic embolism resulting from Aspergillus aortitis in an immunocompetent patient.

INTRODUCTION: Cerebral infarction secondary to Aspergillus arteritis or septic embolism is an exceptional finding. We present a case of multiple systemic embolism and cerebral infarction resulting from Aspergillus aortitis in an immunocompetent patient. PATIENT: A 65-year-old male with hypertension, hyperglycaemia and myocardial infarction with aorto-coronary by-pass surgery three years before admission, that suffered cerebral infarction in middle right cerebral artery territory and right cubital artery embolism. One month later he presented abrupt increase of his left hemiparesia and left central facial palsy associated with fever of unknown origin. Laboratory test, cranial CT and echocardiogram were performed. He died ten days later. RESULTS: Hemogram: leucocytes 34.700/microL (85% N, 4.8%L). Cranial CT: cerebral infarction in middle right cerebral artery territory. Transthoracic and transesophageal echocardiogram: moderate left ventricular hypertrophy and slight inferior hypokinesis. Arteriography: complete thrombosis of the left internal carotid. Necropsy: parietal aortic aspergillosis with generalized septic embolisms (brain, kidney, liver, fingers), cerebral infarction in middle right cerebral artery territory and thrombosis of the left carotid siphon with Aspergillus arteritis. CONCLUSIONS: Aspergillosis is an exceptional cause of cerebral infarction, especially in immunocompetent patients, and their diagnosis is complicated, being usually found at necropsy.

[Unilateral papillitis as the presenting symptom of neurosarcoidosis]. / Papilitis unilateral como presentación de neurosarcoidosis.

INTRODUCTION: Sarcoidosis is a granulomatous, multisystemic disease, of unknown etiology. Its prevalence is low, 40 cases by 100,000 inhabitants in Northern European countries. Respiratory symptoms are the most common, however this disease can affect other vital systems. Neurooftalmological manifestations have been reported one out of five cases, such as uveitis, cranial nerves palsy, and choroiditis; papillitis is seldom described. When initial symptoms of sarcoidosis are neurological features (less than 5%), diagnosis is challenging. CASE REPORTS: We present two cases of neurosarcoidosis in our hospital, during the last two years, in patients without previous diagnosis, which came for loss of visual acuity. The diagnostic was achieved by magnetic resonanace white matter lesions hyperintenses in T2, computed tomography thoracic mediastinic adenopathy and elevated determinations of angiotensin-converting enzyme, according to diagnostic criteria of neurosarcoidosis published in 2004. CONCLUSIONS: We propose to include neurosarcoidosis among known etiologies of unilateral papilitis. Since that, determination of angiotensin-converting enzyme should be performed in those cases.

Clasificación de las enfermedades cerebrovasculares / Classification of cerebrovascular diseases

El concepto de enfermedad vascular cerebral se refiere a todo trastorno en el cual un área del encéfalo se afecta de forma transitoria o permanente por una isquemia o hemorragia, como consecuencia de un proceso patológico en uno o más vasos sanguíneos cerebrales. El término Ictus representa de forma genérica un grupo de trastornos que incluyen el infarto cerebral, la hemorragia cerebral y la hemorragia subaracnoidea. "Ictus", es un término latino que al igual que su correspondiente anglosajon "stroke", significa "golpe" y describen perfectamente el carácter brusco y súbito del proceso. Son sinónimos las denominaciones de accidente cerebrovascular, ataque cerebrovascular y apoplejia

[Prognostic factors and outcome of thymectomy in 80 cases of myasthenia gravis]. / Análisis de factores pronósticos y resultados de la timectomía en 80 casos de miastenia gravis.

OBJECTIVES: To analyze the results of thymectomy in our series of patients with myasthenia gravis (MG) and to study the influence of the most common prognostic factors. MATERIAL AND METHODS: Eighty MG patients over a period of 23 years underwent thymectomy consecutively in our hospital. Preoperative assessment included clinical evaluation of muscle weakness, edrophonium testing, electromyography, lung function testing, chest X-rays and CAT scans. Symptoms were assessed by the Osserman scale. The surgical approach was amplified transsternal thymectomy. The prognostic factors studied were sex, age, clinical stage, duration of disease before surgery and histology of the thymus. Clinical outcome was assessed using Millichap and Dodge's criteria. Follow-up was by the chest surgery and neurology departments. RESULTS: Complete remission was observed in 29 cases (36.2%) and significant improvement in 42 (52.5%). Complications developed in 9 patients (11.2%). Most patients were women (53/27) and outcomes for men and women were not statistically different. Mean age was 36 years (range 11-79), with no significant difference in outcome for patients who were older or younger than 60 years of age. Nor were differences evident related to presurgical clinical stage or levels of severity (I + IIa/IIb + III). Differences in outcome were highly significantly related to duration of disease (< 24 / > 24 months) (p = 0.0022), such that outcome was more satisfactory when the pre-surgical course of disease was shorter, provided that no thymoma was present. CONCLUSIONS: Amplified transsternal thymectomy was safe and effective for those patients with MG. When disease had been present for less than two years, the prognosis was better.

[Cerebral arteriopathy with subcortical infarctions and leukoencephalopathy with dominant autosomal inheritance (CADASIL). Clinical and morphological study]. / Arteriopatía cerebral con infartos subcorticales y leucoencefalopatía con herencia autosómica dominante (CADASIL). Estudio clínico y morfológico.

OBJECTIVE: The cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by the recurrence of subcortical infarcts leading to dementia. It is known the genetic and neuroimaging findings, but there are few studies about its histopathology. Our objective had been to study the pathological findings in this arteriopathy. SUBJECTS AND METHODS: We studied two families spreading over four generations. We performed a detailed clinical history, laboratory investigations, neuroimaging study and genetic analysis. Two brain biopsies and one autopsy were done in patients from the two families. RESULTS: Eight affected members, with autosomal dominant inheritance. Age at onset was between 40 and 50 years. This was characterized clinically by recurrent ischemic attacks, headache and subcortical dementia without vascular risk factors. Histopathological findings showed an arteriopathy characterized by a slightly basophilic small arterial granular degeneration of the medial sheath associated with the presence of ballooned smooth muscle cells with clear cytoplasm. CONCLUSION: The histopathological findings of CADASIL show a characteristic arteriopathy that allow a better understanding of its pathogenesis and could contribute for its diagnosis.

Encephalopathy and biopsy-proven cerebrovascular inflammatory changes in a cocaine abuser.

Cocaine abuse is a well known cause of cerebrovascular complications. An inflammatory vasculopathy hypothesis has been proposed, but the medical literature has only reported a few pathological confirmations. We report a case with a biopsy demonstrating cerebral inflammatory vascular changes that are associated with cocaine abuse. A 21-year-old male, a twice weekly cocaine abuser, developed encephalopathy, apraxia and left hemiparesis with hemisensory loss during the first week after his last cocaine intake; postural tremor and dystonia appeared later. Laboratory data were unrevealing. Cerebral angiography showed a lack of vascularization in the left precentral and central arterial groups. A corticomeningeal cerebral biopsy demonstrated perivascular cell collection and transmural lymphomonocytic infiltration of the small cortical vessels. All symptoms improved with corticosteroid treatment, but 4 years later, the patient returned with a worsening of his encephalopathy and a severe memory impairment, emotional lability and apraxia. A cerebral magnetic resonance image (MRI) showed subcortical and periventricular lesions suggesting ischemic damage in small-size vessel areas as well as cortical atrophy. This new case supports the existence of an encephalopathy associated with vascular inflammatory changes in a cocaine abuser, although more clinical and experimental data are necessary to define its physiopathology.

[Association of plasmapheresis and high doses of intravenous immunoglobulins in the treatment of myasthenia gravis]. / Asociación de plasmaféresis y dosis altas de inmunoglobulina intravenosa en el tratamiento de la miastenia gravis.

INTRODUCTION: In the past decade good therapeutic results have been reported with high dosage of intravenous immunoglobulins (Ig i.v.) in various autoimmune disorders, including myasthenia gravis (MG). Plasmapheresis has been used successfully in this disorder on indications similar to those described for the use of Ig i.v.. We have used sequential treatment of plasmapheresis followed by high doses of intravenous gammaglobulin in MG, seeking complementary benefits from the two kinds of treatment. MATERIAL AND METHODS: The sample included 10 patients with MG (7 of Osserman's grade II-B, 1 of II-A and 2 of III). We began treatment with plasmapheresis, and then continued with an i.v. infusion of Ig at a dose of 400 mg/Kg/day for 5 days. To evaluate the response to treatment, we used the classification system for muscle weakness based on the Virginia University modification of Osserman's grades, on the clinical involvement grade scales and on functional activity. RESULTS: All patients showed statistically significant improvement of the parameters studied. Improvement started between the first and sixth day, following administration of Ig i.v. and persisted for the following 16 weeks. CONCLUSIONS: We consider that combined treatment with plasmapheresis and Ig i.v. may synergically potentiate the immunological effects since they have different mechanisms of action. The indication for this is limited to serious clinical conditions resistant to other treatment, to speed recovery.