Frequency and outcome of total anterior circulation strokes without intracranial large-vessel occlusion.

BACKGROUND AND PURPOSE: The percentage of patients with clinical total anterior circulation infarct (TACI) syndrome treated with reperfusion therapies in the absence of intracranial large-vessel occlusion (ILVO) was determined and their characteristics and outcome are described. METHODS: Data from a population-based, prospective, externally audited registry of all stroke patients treated with intravenous thrombolysis (IVT) and endovascular therapies in Catalonia from January 2011 to December 2013 were used. Patients with a baseline TACI and initial stroke severity measured by the National Institute of Health Stroke Scale (NIHSS) ≥ 8, evaluated less than 4.5 h post-onset, for whom a vascular study prior to treatment was available (n = 1070) were selected. Clinical characteristics, outcome and radiological data for patients treated with IVT alone (n = 605) were compared between those with detected ILVO (n = 474) and non-ILVO patients (n = 131). RESULTS: A total of 1070 patients met study criteria; non-ILVO was found in 131 (12.2%). Analysing the 605 patients treated only with IVT, no significant differences were found between non-ILVO and ILVO patients in age, sex, risk factors, time-to-treatment and type of radiological studies performed. Although non-ILVO patients had lower initial stroke severity (P < 0.001) and a better prognosis (P = 0.001), 51.3% had a poor outcome and 16% were deceased at 90 days. In 66.4% of patients without ILVO, a recent anterior territorial infarct was detected. CONCLUSIONS: Intracranial artery patency was observed in 12.2% of TACI patients evaluated within 4.5 h. Although absence of ILVO was associated with slightly better prognosis, more than half had a poor outcome at 3 months.

Applicability of the SPAN-100 index in a prospective and contemporary cohort of patients treated with intravenous rtPA in Catalonia. / Aplicabilidad del índice SPAN-100 en una cohorte prospectiva y contemporánea de pacientes tratados con rtPA por vía intravenosa en Cataluña.

BACKGROUND: Prognostic scales can be helpful for selecting patients for reperfusion treatment. This study aims to assess the prognostic ability of the recently published SPAN-100 index in a large cohort of stroke patients treated with intravenous thrombolysis (IV rtPA). METHODS: Using data from the prospective registery of all reperfusion treatments administered in Catalonia, we selected patients treated with IV rtPA alone between 2011 and 2012. The SPAN-100 index was calculated as the sum of age (years) and NIHSS score, and patients in the cohort were classified as SPAN-100 positive [≥ 100] or SPAN-100 negative [< 100]. We measured raw and adjusted rates of symptomatic intracerebral haemorrhage (SICH), mortality, and 3-month functional outcome (mRS 0-2) for each SPAN-100 category. Area under the ROC curve was calculated to predict the main outcome measures. RESULTS: We studied 1685 rtPA-treated patients, of whom 1405 (83%) were SPAN-100 negative. The SICH rates adjusted for sex, pre-stroke mRS, hypertension, diabetes, dyslipidaemia, ischaemic heart disease, heart failure, atrial fibrillation, prior TIA/stroke and time to thrombolysis did not differ between groups, but likelihood of functional independence (mRS 0-2) at 3 months was nearly 8 times higher in the SPAN-100 negative group than in the positive group. Furthermore, the 3-month mortality rate was 5 times higher in the SPAN-100 positive group. ROC curve analysis showed high specificities for predicting both functional independence and 3-month mortality for a cut-off point of 100. CONCLUSION: The SPAN-100 index is a simple and straightforward method that may be useful for selecting candidates for rtPA treatment in doubtful cases, and for informing patients and their relatives about likely outcomes.

Neuroimaging in small vessel disease.

The objective of this article is to review the literature on neuroimaging in small vessel disease. A review was carried out through the Pubmed search engine, without a filter of years, using terms such as: cerebral small vessel disease; white matter hyperintensity; brain microbleed; WBC. Small vessel disease is the most common vascular pathology. Its basis is in the affectation of the small cerebral vessels that eventually causes an alteration in the blood-brain barrier. Its clinical implication is highly relevant. Using magnetic resonance imaging, different expressions of the disease have been observed, such as white matter hyperintensities, microbleeds or lacunar infarcts. Other more recent techniques, such as brain blood flow measurements, are helping to increase understanding of the pathophysiology of this disease.

Dyslipidemias and stroke prevention: Recommendations of the Study Group of Cerebrovascular Diseases of the Spanish Society of Neurology.

OBJECTIVE: We present an update of the Spanish Society of Neurology's recommendations for prevention of both primary and secondary stroke in patients with dyslipidaemia. DEVELOPMENT: We performed a systematic review to evaluate the main aspects of the management of dyslipidaemias in primary and secondary stroke prevention and establish a series of recommendations. CONCLUSIONS: In primary prevention, the patient's vascular risk should be determined in order to define target values for low-density lipoprotein cholesterol. In secondary prevention after an atherothrombotic stroke, a target value <55 mg/dL is recommended; in non-atherothombotic ischaemic strokes, given the unclear relationship with dyslipidaemia, target value should be established according to the vascular risk group of each patient. In both primary and secondary prevention, statins are the drugs of first choice, and ezetimibe and/or PCSK9 inhibitors may be added in patients not achieving the target value.

Stroke prevention in patients with arterial hypertension: Recommendations of the Spanish Society of Neurology's Stroke Study Group.

OBJECTIVE: To update the recommendations of the Spanish Society of Neurology on primary and secondary stroke prevention in patients with arterial hypertension. DEVELOPMENT: We proposed several questions to identify practical issues for the management of blood pressure (BP) in stroke prevention, analysing the objectives of blood pressure control, which drugs are most appropriate in primary prevention, when antihypertensive treatment should be started after a stroke, what levels we should aim to achieve, and which drugs are most appropriate in secondary stroke prevention. We conducted a systematic review of the PubMed database and analysed the main clinical trials to address these questions and establish a series of recommendations. CONCLUSIONS: In primary stroke prevention, antihypertensive treatment should be started in patients with BP levels >  140/90 mmHg, with a target BP of < 130/80 mmHg. In secondary stroke prevention, we recommend starting antihypertensive treatment after the acute phase (first 24 hours), with a target BP of < 130/80 mmHg. The use of angiotensin-II receptor antagonists or diuretics alone or in combination with angiotensin-converting enzyme inhibitors is preferable.

Recommendations of the Spanish Society of Neurology for the prevention of stroke. Interventions on lifestyle and air pollution.

OBJECTIVE: To update the recommendations of the Spanish Society of Neurology regarding lifestyle interventions for stroke prevention. DEVELOPMENT: We reviewed the most recent studies related to lifestyle and stroke risk, including randomised clinical trials, population studies, and meta-analyses. The risk of stroke associated with such lifestyle habits as smoking, alcohol consumption, stress, diet, obesity, and sedentary lifestyles was analysed, and the potential benefits for stroke prevention of modifying these habits were reviewed. We also reviewed stroke risk associated with exposure to air pollution. Based on the results obtained, we drafted recommendations addressing each of the lifestyle habits analysed. CONCLUSIONS: Lifestyle modification constitutes a cornerstone in the primary and secondary prevention of stroke. Abstinence or cessation of smoking, cessation of excessive alcohol consumption, avoidance of exposure to chronic stress, avoidance of overweight or obesity, a Mediterranean diet supplemented with olive oil and nuts, and regular exercise are essential measures in reducing the risk of stroke. We also recommend implementing policies to reduce air pollution.

Stroke prevention in patients with type 2 diabetes or prediabetes. Recommendations from the Cerebrovascular Diseases Study Group, Spanish Society of Neurology. / Prevención de ictus en pacientes con diabetes mellitus tipo 2 o prediabetes. Recomendaciones del Grupo de Estudio de Enfermedades Cerebrovasculares de la Sociedad Española de Neurología.

OBJECTIVE: To update the Spanish Society of Neurology's guidelines for stroke prevention in patients with type 2 diabetes or prediabetes, analysing the available evidence on the effect of metabolic control and the potential benefit of antidiabetic drugs with known vascular benefits in addition to conventional antidiabetic treatments in stroke prevention. DEVELOPMENT: PICO-type questions (Patient, Intervention, Comparison, Outcome) were developed to identify practical issues in the management of stroke patients and to establish specific recommendations for each of them. Subsequently, we conducted systematic reviews of the PubMed database and selected those randomised clinical trials evaluating stroke as an independent variable (primary or secondary). Finally, for each of the PICO questions we developed a meta-analysis to support the final recommendations. CONCLUSIONS: While there is no evidence that metabolic control reduces the risk of stroke, some families of antidiabetic drugs with vascular benefits have been shown to reduce these effects when added to conventional treatments, both in the field of primary prevention in patients presenting type 2 diabetes and high vascular risk or established atherosclerosis (GLP-1 agonists) and in secondary stroke prevention in patients with type 2 diabetes or prediabetes (pioglitazone).

Dyslipidemias and stroke prevention: recommendations of the Study Group of Cerebrovascular Diseases of the Spanish Society of Neurology. / Dislipidemias y prevención del ictus: recomendaciones del Grupo de Estudio de Enfermedades Cerebrovasculares de la Sociedad Española de Neurología.

OBJECTIVE: We present an update of the Spanish Society of Neurology's recommendations for prevention of both primary and secondary stroke in patients with dyslipidaemia. DEVELOPMENT: We performed a systematic review to evaluate the main aspects of the management of dyslipidaemias in primary and secondary stroke prevention and establish a series of recommendations. CONCLUSIONS: In primary prevention, the patient's vascular risk should be determined in order to define target values for low-density lipoprotein cholesterol. In secondary prevention after an atherothrombotic stroke, a target value <55mg/dL is recommended; in non-atherothombotic ischaemic strokes, given the unclear relationship with dyslipidaemia, target value should be established according to the vascular risk group of each patient. In both primary and secondary prevention, statins are the drugs of first choice, and ezetimibe and/or PCSK9 inhibitors may be added in patients not achieving the target value.

The response to IV rt-PA in very old stroke patients.

The use of rtPA in stroke patients aged >80 years remains controversial and it is debated whether there are sex-based differences in the response to rtPA. We assessed the clinical value of thrombolytic therapy in patients aged >80 years (elderly group) in comparison with a non-elderly group, and evaluated the existence of sex differences in the response to rtPA. All consecutive patients (n = 157) treated with rtPA were prospectively assessed since July 2001, including 49 elderly patients who fulfilled the National Institute of Neurological Disorders and Stroke (NINDS) criteria. Changes of the National Institute of Health Stroke Scale (NIHSS) score at 1 h, 24 h, and 7 days after rtPA administration, favourable outcome at day 90 [(modified Rankin Scale) mRS 0-1, or 2 if mRS = 2 before the stroke], symptomatic bleedings, and death rates were compared between elderly and non-elderly patients. Using logistic regression, baseline NIHSS score [odds ratio (OR) 0.59, 95% confidence interval (CI) 0.41-0.84] was an independent predictor of favourable outcome, but not sex (OR 0.72, 95% CI 0.33-1.56), or age >80 years (OR 0.74, 95% CI 0.32-1.70). The rates of clinical improvement, mortality, or symptomatic CNS bleeding were also unrelated to age and sex. In conclusion, the response to IV rtPA is not impaired in elderly stroke patients and male and female are equally responsive.

No association of the Val66Met polymorphism of brain-derived neurotrophic factor (BDNF) to multiple sclerosis.

Brain-derived neurotrophic factor (BDNF), a neurotrophin produced by neurons and immune cells, promotes neuronal survival and repair during development and after CNS injury. The BDNF-Val66Met polymorphism is functional and induces abnormal intracellular trafficking and decreased BDNF release. Therefore, we investigated the impact of the BDNF-Val66Met polymorphism on the susceptibility and clinical course in a case-control study of 224 multiple sclerosis (MS) Spanish patients and 177 healthy controls. We found no evidence for association to susceptibility or severity of the disease in our population. Moreover, we did not observe, in a subgroup of 12 MS patients, that the methionine substitution at position 66 in the prodomain had negative impact in the capacity to produce BDNF by peripheral blood mononuclear cells (PBMC).

Effect of glatiramer acetate (Copaxone) on the immunophenotypic and cytokine profile and BDNF production in multiple sclerosis: a longitudinal study.

We assessed the effect of glatiramer acetate (GA) on the immunophenotypic and cytokine profile and the BDNF production by peripheral blood mononuclear cells, and their association with the clinical response in 19 naïve-treated MS patients prospectively followed-up after GA therapy. Two patients withdrew the therapy. After a median follow-up of 21 months, twelve were considered responders and five as non-responders. Non-responder patients had significant longer disease duration and a higher EDSS score at baseline. In the responder group, a significant decrease in the percentage of INF-gamma producing total lymphocytes, CD4+ and CD8+ T cells, and reduced percentage of IL-2 producing CD4+ and CD8+ T cells were observed at 12, 18 and 24 months. These changes were associated with a significant increase in the percentage of CD3+, CD4+ and CD4(+) CD45RA(+) T cells, and BDNF production from month 6 that remained significant throughout the study. We did not observe significant changes in the nonresponder group for any of the parameters studied. Our data suggest that GA treatment induces a downmodulation of proinflammatory cytokines associated with the regulation of the peripheral T cell compartment and with increased production of BDNF that might be related to the clinical response.

[Clinical outcome 6 years after autologous hematopoietic stem cell transplantation in multiple sclerosis]. / Resultado clínico a 6 años del trasplante autólogo de progenitores hematopoyéticos en la esclerosis múltiple.

INTRODUCTION: Autologous hematopoietic stem cell transplantation (AHSCT) remains as an experimental treatment for severe forms of multiple sclerosis (MS). We describe the clinical outcome of 14 patients included in a protocol of AHSCT after a median follow-up period of 6 years. METHODS: 14 patients (5 relapsing-remitting and 9 secondary progressive) with a median number of relapses in the year before of 3 (1-7), Expanded Disability Status Scale (EDSS) of 6 (4.5-6.5) and decile of the multiple Sclerosis Severity Store (MSSS) 9 (7-10) were included. The procedure included carmustine, cyclophosphamide, antithymocyte globulin and T-cell depletion by CD34+ selection. RESULTS: The 4.5-year progression-free survival was 71%. The 6 year actuarial probability of progression-free survival was 62.5% and the disease activity-free survival of 7.1%. The median EDSS was 6 (4-8.5) and the MSSS 8 (5-10). Only 2 patients presented enhanced T1 lesions. No long-term complications related to the procedure were observed. CONCLUSION: AHSCT cannot be deemed a curative treatment but may cause prolonged stabilisation or change the aggressive course of the disease.

Prevalence of restless legs syndrome and REM sleep behavior disorder in multiple sclerosis.

A total of 135 consecutive, unrelated, multiple sclerosis (MS) patients were interviewed for symptoms suggestive of restless legs syndrome (RLS) and REM sleep behavior disorder (RBD), using semi-structured questionnaires. Some 118 unrelated healthy controls of similar sex and age distribution were included for comparison. Patients and controls with equivocal symptoms were re-evaluated by a sleep disorders specialist and video-polisomnography in those who fulfilled the criteria for RBD. We did not find significant differences in frequency (13.3 versus 9.3%), proportion of females (66.7 versus 58.5%), and mean age (42.1+/-12.6 versus 43+/-7.8 years) among MS patients and controls with RLS. RBD was found in three patients (1.4%), one associated with antidepressant intake, but in none of the controls. Our study shows that RLS in MS is not more frequent than in the general population, and that RBD, although uncommon, may occur in the setting of this neurological disease.