Clinical and neuroimaging characteristics of 14 patients with prionopathy: a descriptive study.

INTRODUCTION: Prionopathy is the cause of 62% of the rapidly progressive dementias (RPD) in which a definitive diagnosis is reached. The variability of symptoms and signs exhibited by the patients, as well as its different presentation, sometimes makes an early diagnosis difficult. METHODS: Patients withdiagnosis of definite or probable prionopathy during the period 1999-2012 at our hospital were retrospectively reviewed.The clinical features and the results of the complementary tests (14-3-3 protein, EEG, MRI, FDG-PET, and genetic analysis) were evaluated in order to identify some factors that may enable an earlier diagnosis to be made. RESULTS: A total of 14 patients are described: 6 with definite sporadic Creutzfeldt-Jakob (sCJD) disease, 3 with probable sCJD, 4 with fatal familial insomnia, and 1 with the new variant. The median age at diagnosis was 54 years old. The mean survival was 9.5 months. Mood disorder was the most common feature, followed by instability and cognitive impairment. 14-3-3 protein content in the cerebrospinal fluid was positive in 7 of 11 patients, and the EEG showed typical signs in 2 of 12 patients. Neuroimaging (FDG-PET, MRI) studies suggested the diagnosis in 13 of the 14 patients included. CONCLUSIONS: Most patients presenting with RPD suffer from a prion disease. In our series the most useful complementary tests were MRI and FDG-PET, being positive in 13 of the 14 patients studied.

Guidelines for the preventive treatment of ischaemic stroke and TIA (II). Recommendations according to aetiological sub-type.

BACKGROUND AND 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 the available evidence on ischaemic stroke and TIA prevention according to aetiological subtype. Levels of evidence and recommendation levels are based on the classification of the Centre for Evidence-Based Medicine. RESULTS: In atherothrombotic IS, antiplatelet therapy and revascularization procedures in selected cases of ipsilateral carotid stenosis (70%-90%) reduce the risk of recurrences. In cardioembolic IS (atrial fibrillation, valvular diseases, prosthetic valves and myocardial infarction with mural thrombus) prevention is based on the use of oral anticoagulants. Preventive therapies for uncommon causes of IS will depend on the aetiology. In the case of cerebral venous thrombosis oral anticoagulation is effective. CONCLUSIONS: We conclude with recommendations for clinical practice in prevention of IS according to the aetiological subtype presented by the patient.

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.

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.

What happens to medical articles submitted in Spanish that are not accepted for publication?

INTRODUCTION: The fate of manuscripts submitted and subsequently rejected by Spanish-language journals is unknown. The present study was designed to determine whether or not articles submitted to Neurología are published following rejection, and if so, where. METHODS: We searched Medline in late April 2012 and also analysed all manuscripts rejected by Neurología between October 2004 and April 2012 according to that journal's two databases. In that period, 1277 articles were submitted to the journal. RESULTS: Of the 271 manuscripts rejected by Neurología, 54 articles (19.9%) were published in other journals. Neurology journals published 31 of the manuscripts (57.4%); 43 manuscripts (79.6%) appeared in Spanish-language journals. Of the rejected manuscripts, 24.1% of the originals, 8.3% of the letters to the editor, 28.9% of the case reports, 22.6% of the reviews and 6.3% of the images were published. Authors with three previously published articles on the same topic managed to publish their manuscripts in 34% of the cases, compared to only 11.8% of authors with fewer published articles (P < .0001). Of the total manuscripts rejected between 2004 and 2010, 24.8% were eventually published. The median time lapse between article submission and publication was 13 months (range, 2-59 months). CONCLUSION: Manuscripts rejected by Neurología are often published in other journals, but this scenario is not as common as in English-language journals. In the case of Neurología, the editor's decision to reject an article is more significant than it would be in an English-language journal because the author will have fewer additional possibilities of having the manuscript published.

Clinical practice guidelines in intracerebral haemorrhage.

Intracerebral haemorrhage accounts for 10%-15% of all strokes; however it has a poor prognosis with higher rates of morbidity and mortality. Neurological deterioration is often observed during the first hours after onset and determines poor prognosis. Intracerebral haemorrhage, therefore, is a neurological emergency which must be diagnosed and treated properly as soon as possible. In this guide we review the diagnostic procedures and factors that influence the prognosis of patients with intracerebral haemorrhage and we establish recommendations for the therapeutic strategy, systematic diagnosis, acute treatment and secondary prevention for this condition.

Central sleep apnea is associated with increased risk of ischemic stroke in the elderly.

OBJECTIVES: Sleep apnea/hypopnea syndrome is a well-recognized independent risk factor for stroke in middle-aged population, but controversy remains in older subjects. We examined the possible association between different respiratory parameters and risk of stroke in a prospective population-based cohort of 394 stroke-free elderly subjects. MATERIAL AND METHODS: Fully overnight polysomnography was performed at baseline. Over the 6 year follow-up period, 20 ischemic strokes occurred. Differences in stroke-free survival between subjects according to central apnea index (CAI) were assessed. RESULTS: We just observed association with incident ischemic stroke on central sleep apnea (CSA) episodes. Obstructive sleep apnea, time passed under 90% oxygen saturation, or arousal index were not associated. The event-free survival was lowest in the highest CAI group. This association was independent of any other vascular risk factors. CONCLUSIONS: CSA is the specific respiratory event associated with stroke in the elderly. Additionally, CSA could be a marker of silent brain ischemia, as a sign of disturbed regulation of central respiratory mechanisms, tentatively of ischemic origin.

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.

Neurophysiology training in the Neurology Specialist Education Program in Spain.

INTRODUCTION: The training period in neurophysiology is a substantial part of the Neurology Specialist Program in Spain. The National Neurology Committee (La Comisión Nacional de Neurología (CNN), which is the body reporting to the Ministries of Health and Education, must ensure compliance to the Program. MATERIAL AND METHODS: During the first trimester of 2008, the CNN sent a questionnaire, in which there was a question asking about this training period, to each of the managers of the 69 teaching units accredited for neurology training in Spain, for them to answer. RESULTS: Of the 69 questionnaires issued, 49 were received completed, which was a response rate of 71%. The neurophysiology training period of the neurology specialist program in Spain was carried out in the same hospital in 44 teaching unit (90%): the remaining 5 sent their neurology trainees to 4 different hospitals. The Unit that carried out the neurophysiology training period was incorporated into the Neurology Department in 27 (55%) cases, and the formula was mixed in 3 (6%). A total of 69% of tutors were satisfied with the training, but was 90% in the hospitals where the unit was integrated into Neurology, and was 65% where this relationship did not exist. The neurologists in training were informed about EEG in 49% of education units, performed EMG/ENG 57%, and informed about evoked potentials in 35% after their training period. CONCLUSIONS: Although the level of satisfaction is high, the level of responsibility assumed by the neurologists in training during their rotation into neurophysiology does not appear to comply to the demands laid out in the training program, particularly in these units not integrated into Neurology Departments.

Activation of the brainstem but not of the hypothalamus in hemicrania continua without autonomic symptoms.

A 64-year-old woman presented with a 6-month history of right-sided continuous headache, without autonomic symptoms and complete response to indomethacin. Clinical examination and structural brain imaging were normal. A diagnosis of hemicrania continua (HC) was made. We sought to determine the brain structures active during the pain in a patient who met all of the diagnostic criteria for HC with the exception of autonomic symptoms. A brain positron emission tomography study was performed during pain, and completely pain-free after indomethacin administration. Comparing the pain with pain-free states, the region of the dorsal pons was significantly activated. There was no activation in the hypothalamus, as previously reported in HC with autonomic symptoms. Although definitive conclusions can not be drawn from a single observation, the lack of autonomic symptoms along with the absence of hypothalamic activation suggests that the clinical presentation may predict the pattern of brain activation in primary headache syndromes.

[The problem of neurological emergencies and the need for specific neurology shifts]. / Urgencias neurológicas y guardias de Neurología.

In recent years different studies have highlighted a progressive increase in the demand for neurological care in emergency departments. To analyze the convenience of specific neurology shifts or the role that the neurologist should play in the emergency department, it is necessary to answer questions such as: What is the demand for emergency neurological care? What are the most frequent neurological emergencies? Who should attend to neurological emergencies and why? Are specific neurology shifts necessary? Neurological emergencies account for between 2.6% and 14% of medical emergencies. Stroke represents a third of all neurological emergencies, while the diagnoses of acute cerebrovascular disease, epilepsy and cephalea constitute 50% of all neurological care in the emergency department. On the basis of quality of care criteria and professional competence, the best care for patients with a neurological emergency is provided by a specialist in neurology. The implementation of specific neurology shifts, with a 24 hour physical presence, is associated with greater quality of care, better diagnostic and therapeutic orientation from the moment the patient arrives in emergency department, reduces unnecessary admissions, reduces costs and strengthens the neurology service.

[Stroke in the XXI century. Emergency care]. / El ictus en el siglo XXI. Tratamiento de urgencia.

Cerebrovascular diseases have reached epidemic proportions worldwide. They are the major cause of mortality in developed countries, accounting for over one-quarter of worldwide documented deaths, and the leading cause of severe disability in adults. Given that Spain will become one of the countries most affected by population ageing, an increase in the incidence of these diseases is expected in coming years. Several studies have reported that public levels of awareness of stroke warning signs, symptoms and risk factors are relatively low. Information campaigns aimed at increasing these levels of awareness and considering stroke as a neurological emergency are needed. The stroke code is a system which allows rapid identification, notification, and transfer of stroke patients to the emergency units. Technological advances in stroke diagnosis, and the development of effective therapeutic measures, such as thrombolytics, require a coordinated multidisciplinary approach. Treating patients in Stroke Units is the most effective and efficient approach in acute ischemic or hemorrhagic stroke management. In coming years research advances will provide new and better strategies in acute stroke treatment.

[Headache in the emergency department]. / Cefalea en urgencias.

Headache is among the most frequent neurological symptoms in the Emergency department. Although most of the patients suffer from primary headaches (migraine), an acute headache might be the only symptom of a serious disease, such as subarachnoid haemorrhage. The physician's task is to make the diagnosis, carry out an appropriate selection of the patients who require further diagnostic evaluation and relieve the pain. An accurate history will identify most of the patients with secondary headaches. Clinicians should suspect secondary causes in sudden onset headache, headache in patients aged over 50 years, and also in those patients with abnormalities on neurological examination.

[Study of vascular risk in Navarre: objectives and design. Prevalence of metabolic syndrome and of vascular risk factors]. / Estudio de riesgo vascular en Navarra: objetivos y diseño. Prevalencia del síndrome metabólico y de los factores mayores de riesgo vascular.

BACKGROUND: To determine in a representative sample of the population the prevalence of risk factors and metabolic syndrome; their association with sub-clinical atherosclerotic lesions and their impact on cardiocerebrovascular disease 10 years after. MATERIAL AND METHODS: (Phase 1) Cross sectional survey of a random sample stratified by age and sex of the population of Navarre aged between 35 and 84. Antecedents, risk factors, physical and analytical exploration. (Phase II) Ten year follow-up cohort study, in 500 exposed to MS and 500 not exposed persons, aged between 45 and 74 years; with an 82.25% power to detect a risk ratio of 2; with analytical and image markers of sub-clinical atherosclerosis. (Phase III) Follow up of vascular events at ten years. RESULTS: The subjects recruited were 6,553; excluded or not found 871; the final sample was 5,682 (2,644 men and 3,038 women); 4,168 (73,4%) took part in the study. The prevalence of MS was 22.1% (95%CI 20.5 - 23.7) for men and 17,2% (95%CI 15.8 - 18.5) for women. The main cardiovascular RF were high compared to other geographical areas except for HDL cholesterol. The rate was 8.5% (95%CI 7.4 - 9.6) for men and 1.7% (95%CI 1.3 - 2.2) CONCLUSIONS: There are important differences in risk between sex, being worst for men. The high figures for HDL cholesterol and the low prevalence of MS might mean a lower risk of vascular events in Navarra.

EFNS guideline on neuroimaging in acute stroke. Report of an EFNS task force.

Neuroimaging techniques are necessary for the evaluation of stroke, one of the leading causes of death and neurological impairment in developed countries. The multiplicity of techniques available has increased the complexity of decision making for physicians. We performed a comprehensive review of the literature in English for the period 1965-2005 and critically assessed the relevant publications. The members of the panel reviewed and corrected an initial draft, until a consensus was reached on recommendations stratified according to the European Federation of Neurological Societies (EFNS) criteria. Non-contrast computed tomography (CT) scan is the established imaging procedure for the initial evaluation of stroke patients. However, magnetic resonance imaging (MRI) has a higher sensitivity than CT for the demonstration of infarcted or ischemic areas and depicts well acute and chronic intracerebral hemorrhage. Perfusion and diffusion MRI together with MR angiography (MRA) are very helpful for the acute evaluation of patients with ischemic stroke. MRI and MRA are the recommended techniques for screening cerebral aneurysms and for the diagnosis of cerebral venous thrombosis and arterial dissection. For the non-invasive study of extracranial vessels, MRA is less portable and more expensive than ultrasonography but it has higher sensitivity and specificity for carotid stenosis. Transcranial Doppler is very useful for monitoring arterial reperfusion after thrombolysis, for the diagnosis of intracranial stenosis and of right-to-left shunts, and for monitoring vasospasm after subarachnoid hemorrhage. Currently, single photon emission computed tomography and positron emission tomography have a more limited role in the evaluation of the acute stroke patient.

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.

Functional interaction between dopamine D1 and D2 receptors in 'MPTP' monkeys.

We have studied the motor response induced by independent administration of 4 different doses of a dopamine D2 [(+)-PHNO] and a dopamine D1 (CY 208-243) receptor agonist in 5 MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) monkeys. Both drugs had similar antiparkinsonian effects and both elicited choreic dyskinesias. Simultaneous administration of (+)-PHNO [(+)-4-propyl-9-hydroxynaphthoxazine] and CY 208-243 [(-)4,6,6a,7,8,12b-hexahydro-7-methylindolo[4,3a-b]phenan thyxidine] did not result in modification of the dose-response curve induced by each dopamine receptor agonist given alone. Pretreatment with the dopamine D1 receptor antagonist SCH 23390 (0.8 mg/kg) and the dopamine D2 receptor antagonist sulpiride (60 mg/kg) reduced the magnitude and the duration of the motor response induced by (+)-PHNO and CY 208-243, respectively, but did not modify the intensity and characteristics of choreic dyskinesias. These results demonstrate that the motor effects and the dyskinesias cannot be dissociated by selective dopamine D1 and D2 receptor stimulation. It appears that stimulation of dopamine D1 and D2 receptors by endogenous dopamine is required to obtain the full motor response induced by selective dopamine receptor agonists as demonstrated by the reduction of the motor improvement found after pretreatment with SCH 23390 and sulpiride.