Cerebral hemodynamic changes at basilar artery in patients with obstructive sleep apnea syndrome. A case-control study.

INTRODUCTION: Obstructive sleep apnea syndrome (OSAS) is characterized in polysomnography by recurrent airflow obstruction during sleep. The underlying pathogenic mechanisms of neuropsychological and cerebrovascular events in patients with OSAS have not been clarified unequivocally. MATERIAL AND METHODS: Case-control study to evaluate the cerebral vasomotor reactivity assessed by breath-holding maneuver at basilar artery in patients with OSAS compared to control subjects. RESULTS: The study included 76 patients with OSAS and 76 controls. Vascular risk factors (arterial hypertension, diabetes mellitus, hypercholesterolemia, smoking), age, gender, coronary, and peripheral arterial diseases were similar in both groups. Patients with OSAS had breath-holding test values (31.9 ± 13.35%) lower than controls (39.06 ± 13.16%), (P = 0.001). Patients with OSAS had higher systolic and diastolic blood pressure both basal and apnea and also a higher basal heart rate. CONCLUSIONS: Altered cerebral hemodynamics together with increased blood pressure values in patients with OSAS may play a role in the association between this disease and the development of cerebrovascular events. This implies that this disease should be identified through guide symptoms such as snoring, sleep apnea, and daytime sleepiness in all patients who consult for these symptoms to reduce the number of cerebrovascular events.

[Ultrasound measurement of carotid stenosis: recommendations from the Spanish Society of Neurosonology]. / Cuantificación ultrasonográfica de la estenosis carotídea: recomendaciones de la Sociedad Española de Neurosonología.

In Spain, approximately 28% of ischaemic strokes have an atherothrombotic cause, and most are due to carotid stenosis. Ultrasound is the most commonly used technique for diagnosing carotid stenosis. Changes in blood flow velocity at the point of maximum stenosis, together with haemodynamic changes in proximal regions (common carotid artery) and distal regions (poststenotic internal carotid, ophthalmic artery, and the circle of Willis), allow us to measure carotid stenosis precisely. This review explains the methodology to be followed when evaluating carotid stenosis ultrasonographically, according to the recommendations from the Spanish Society of Neurosonology (SONES). We review the findings that permit us to measure the degree of extracranial carotid stenosis using both carotid and transcranial ultrasound, with particular emphasis on the importance of assessing indirect signs.

Characteristics of stroke units and stroke teams in Spain in 2018. Pre2Ictus project.

INTRODUCTION: The aim of this work is to describe the characteristics of stroke units and stroke teams in Spain. METHODS: We performed a cross-sectional study based on an ad-hoc questionnaire designed by 5 experts and addressed to neurologists leading stroke units/teams that had been operational for ≥ 1 year. RESULTS: The survey was completed by 43 stroke units (61% of units in Spain) and 14 stroke teams. A mean (standard deviation) of 4 (3) neurologists were assigned to each stroke unit/team; 98% of stroke units (and 38% of stroke teams) have an on-call neurologist available 24 hours a day, 98% of units (79% of stroke teams) included specialised nurses, 86% of units (71% of stroke teams) included a social worker, and 81% of units (71% of stroke teams) included a rehabilitation physician. Most stroke units (80%) had 4--6 beds with continuous non-invasive monitoring. The mean number of unmonitored beds was 14 (8) for stroke units and 12 (7) for stroke teams. The mean duration of non-invasive monitoring was 3 (1) days. All stroke units and 86% of stroke teams had intravenous thrombolysis available, and 81% of stroke units and 21% of stroke teams were able to perform mechanical thrombectomy, whereas the remaining centres had referral pathways in place. Telestroke systems were in place at 44% of stroke units, providing support to a mean of 4 (3) centres. Activity is recorded in clinical registries by 77% of stroke units and 50% of stroke teams, but less than 75% of data is completed in 25% of cases. CONCLUSIONS: Most stroke units/teams comply with the current recommendations. The systematic use of clinical registries should be improved to further improve patient care.

Epidemiology of ataxia and hereditary spastic paraplegia in Spain: A cross-sectional study.

INTRODUCTION: Ataxia and hereditary spastic paraplegia are rare neurodegenerative syndromes. We aimed to determine the prevalence of these disorders in Spain in 2019. PATIENTS AND METHODS: We conducted a cross-sectional, multicentre, retrospective, descriptive study of patients with ataxia and hereditary spastic paraplegia in Spain between March 2018 and December 2019. RESULTS: We gathered data from a total of 1933 patients from 11 autonomous communities, provided by 47 neurologists or geneticists. Mean (SD) age in our sample was 53.64 (20.51) years; 938 patients were men (48.5%) and 995 were women (51.5%). The genetic defect was unidentified in 920 patients (47.6%). A total of 1371 patients (70.9%) had ataxia and 562 (29.1%) had hereditary spastic paraplegia. Prevalence rates for ataxia and hereditary spastic paraplegia were estimated at 5.48 and 2.24 cases per 100 000 population, respectively. The most frequent type of dominant ataxia in our sample was SCA3, and the most frequent recessive ataxia was Friedreich ataxia. The most frequent type of dominant hereditary spastic paraplegia in our sample was SPG4, and the most frequent recessive type was SPG7. CONCLUSIONS: In our sample, the estimated prevalence of ataxia and hereditary spastic paraplegia was 7.73 cases per 100 000 population. This rate is similar to those reported for other countries. Genetic diagnosis was not available in 47.6% of cases. Despite these limitations, our study provides useful data for estimating the necessary healthcare resources for these patients, raising awareness of these diseases, determining the most frequent causal mutations for local screening programmes, and promoting the development of clinical trials.

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.

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 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.

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).

Epidemiology of ataxia and hereditary spastic paraplegia in Spain: a cross-sectional study. / Mapa epidemiológico transversal de las ataxias y paraparesias espásticas hereditarias en España.

INTRODUCTION: Ataxia and hereditary spastic paraplegia are rare neurodegenerative syndromes. We aimed to determine the prevalence of these disorders in Spain in 2019. PATIENTS AND METHODS: We conducted a cross-sectional, multicentre, retrospective, descriptive study of patients with ataxia and hereditary spastic paraplegia in Spain between March 2018 and December 2019. RESULTS: We gathered data from a total of 1.809 patients from 11 autonomous communities, provided by 47 neurologists or geneticists. Mean (SD) age in our sample was 53.64 (20.51) years; 920 patients were men (50.8%) and 889 were women (49.2%). The genetic defect was unidentified in 920 patients (47.6%). A total of 1371 patients (70.9%) had ataxia and 562 (29.1%) had hereditary spastic paraplegia. Prevalence rates for ataxia and hereditary spastic paraplegia were estimated at 5.48 and 2.24 cases per 100 000 population, respectively. The most frequent type of dominant ataxia in our sample was SCA3, and the most frequent recessive ataxia was Friedreich ataxia. The most frequent type of dominant hereditary spastic paraplegia in our sample was SPG4, and the most frequent recessive type was SPG7. CONCLUSIONS: In our sample, the estimated prevalence of ataxia and hereditary spastic paraplegia was 7.73 cases per 100 000 population. This rate is similar to those reported for other countries. Genetic diagnosis was not available in 47.6% of cases. Despite these limitations, our study provides useful data for estimating the necessary healthcare resources for these patients, raising awareness of these diseases, determining the most frequent causal mutations for local screening programmes, and promoting the development of clinical trials.

Characteristics of stroke units and stroke teams in Spain in 2018. Pre2Ictus project. / Características de las unidades de ictus y equipos de ictus en España en el año 2018. Proyecto Pre2Ictus.

INTRODUCTION: The aim of this work is to describe the characteristics of stroke units and stroke teams in Spain. METHOD: We performed a cross-sectional study based on an ad hoc questionnaire designed by 5 experts and addressed to neurologists leading stroke units/teams that had been operational for ≥ 1 year. RESULTS: The survey was completed by 43 stroke units (61% of units in Spain) and 14 stroke teams. The mean (SD) number of neurologists assigned to each unit/team is 4±3. 98% of stroke units (and 38% of stroke teams) have a neurologist on-call available 24hours, 365 days. 98% of stroke units (79% of stroke teams) have specialised nurse, 95% of units (71% of stroke teams) auxiliary personnel, 86% of units (71% of stroke teams) social worker, 81% of stroke units (71% of stroke teams) have a rehabilitation physician and 81% of stroke units (86% of stroke teams) a physiotherapist. Most stroke units (80%) have 4-6 beds with continuous non-invasive monitoring. The mean number of unmonitored beds is 14 (8) for stroke units and 12 (7) for stroke teams. The mean duration of non-invasive monitoring is 3 (1) days. All stroke units and 86% of stroke teams have intravenous thrombolysis available, and 81% of stroke units and 21% of stroke teams are able to perform mechanical thrombectomy, whereas the remaining centres have referral pathways in place. Telestroke systems are available at 44% of stroke units, providing support to a mean of 4 (3) centres. Activity is recorded in clinical registries by 77% of stroke units and 50% of stroke teams, but less than 75% of data is completed in 25% of cases. CONCLUSIONS: Most stroke units/teams comply with the current recommendations. The systematic use of clinical registries should be improved to further improve patient care.

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.

[Paradoxical arterial gas embolism following a direct incisive injury to the skull]. / Embolismo arterial gaseoso paradojico tras una herida incisa craneal directa.

INTRODUCTION: An arterial gas embolism is defined as the presence of air in the arterial circulation. This is an extremely rare cause of stroke that has been described in a multitude of clinical scenarios, generally related to iatrogenic processes. A clinical case is reported in which the arterial gas embolism occurred after a traumatic brain injury, and the most relevant aspects of diagnosis and aetiopathogenesis are reviewed. CASE REPORT: We report the case of a 52-year-old woman with an open craniofacial wound resulting from an attack with an axe. The initial CT scan found fractures in the left zygomatic, sphenoidal and maxillary arches, as well as pneumocephalus in the cavernous sinuses and the right carotid canal. One hour later, the patient showed a neurological deficit in the right hemisphere, and so a new cranial computed tomography scan with multimodal vascular study was urgently requested, which revealed the mobilisation of the pneumocephalus and ruled out a large vessel arterial occlusion. A shunt study using transcranial Doppler and echocardiography showed the presence of a patent foramen ovale to be the cause of arteriovenous communication that justified an arterial gas embolism. The follow-up CT scan at 48 hours confirmed the appearance of a right parietal ischaemic lesion. CONCLUSION: This case reflects the simultaneous presence of air in the arterial and venous circulation of the brain, as well as the peripheral communication through a patent foramen ovale. This production mechanism is poorly documented in the literature.

TITLE: Embolismo arterial gaseoso paradojico tras una herida incisa craneal directa.Introduccion. El embolismo arterial gaseoso se define como la presencia de aire en la circulacion arterial. Se trata de una causa extremadamente rara de ictus que se ha descrito en multitud de escenarios clinicos, generalmente relacionados con procesos yatrogenos. Se aporta un caso clinico en el que el embolismo arterial gaseoso sucedio tras un traumatismo craneoencefalico, y se revisan los aspectos mas relevantes del diagnostico y la etiopatogenia. Caso clinico. Mujer de 52 años que presentaba herida incisa craneofacial tras una agresion con un hacha. La tomografia computarizada inicial objetivo fractura en los arcos cigomatico, esfenoidal y maxilar izquierdos, asi como neumoencefalo en los senos cavernosos y el canal carotideo derecho. Una hora mas tarde, la paciente mostro un deficit neurologico hemisferico derecho, por lo que se solicito de forma urgente una nueva tomografia computarizada craneal con estudio vascular multimodal, que objetivo la movilizacion del neumoencefalo y descarto una oclusion arterial de gran vaso. Un estudio de shunt mediante Doppler transcraneal y ecocardiografia comprobo la presencia de un foramen oval permeable como causa de comunicacion arteriovenosa que justificaba un embolismo arterial gaseoso. La tomografia computarizada de control a las 48 horas confirmo la aparicion de una lesion isquemica parietal derecha. Conclusion. En este caso queda reflejada la presencia simultanea de aire en la circulacion cerebral arterial y venosa y la comunicacion periferica a traves de un foramen oval permeable. Este mecanismo de produccion esta escasamente documentado en la bibliografia.

Cerebral hemodynamics is altered in patients with sleep apnea/hypopnea syndrome.

According to recent epidemiologic studies, patients with sleep apnea/hypopnea syndrome (SAHS) are at increased risk of cardiovascular diseases, including stroke. However, the mechanisms are not well defined. Nocturnal apneas can trigger acute cerebral ischemia in predisposed patients and impaired vasodilatation is present in SAHS, but few studies have explored vascular cerebral dysfunction and often gave inconclusive results. The aims of our study were to assess whether patients with SAHS have impairment of cerebral hemodynamics with respect to controls, and to investigate a possible relationship with clinical data. We studied two groups, one of 76 SAHS patients and another one of 76 non-SAHS subjects matched for age, sex and main cardiovascular risk factors. All participants underwent a daytime transcranial Doppler study of right middle cerebral artery to record cerebral blood flow velocity and cerebrovascular reactivity by means of breath-holding test (BHT). SAHS patients have a reduction in mean cerebral blood flow velocity (MFV) (52 ± 9 vs 60 ± 12 cms/s, p < 0.001) and BHT (31 ± 12 vs 36 ± 11 %, p = 0.005) when compared to non-SAHS controls. Moreover, MFV correlated negatively with the presence of coronary disease, and BHT with female sex and arterial pressure. On the other hand, in the SAHS group, MFV correlated negatively with oxygen desaturation severity. Patients with SAHS have impaired MFV and cerebrovascular reactivity when compared to controls. Interestingly, poorly controlled or unknown hypertension and severe nocturnal hypoxemia caused additional cerebral hemodynamic disturbances to these patients.

Has the aetiology of ischaemic stroke changed in the past decades? Analysis and comparison of data from current and historical stroke databases. / ¿Se ha producido un cambio en la etiología del ictus isquémico en las últimas décadas? Análisis y comparación de una base de datos de ictus actual frente a las históricas.

OBJECTIVES: We aimed to determine whether the aetiology of ischaemic stroke has changed in recent years and, if so, to ascertain the possible reasons for these changes. PATIENTS AND METHODS: We analysed the epidemiological history and vascular risk factors of all patients diagnosed with ischaemic stroke at Complejo Hospitalario Universitario de Albacete (CHUA) from 2009 to 2014. Ischaemic stroke subtypes were established using the TOAST criteria. Our results were compared to data from the classic Stroke Data Bank (SDB); in addition, both series were compared to those of other hospital databases covering the period between the two. RESULTS: We analysed 1664 patients (58% were men) with a mean age of 74 years. Stroke aetiology in both series (CHUA, SDB) was as follows: atherosclerosis (12%, 9%), small-vessel occlusion (13%, 25%), cardioembolism (32%, 19%), stroke of other determined aetiology (3%, 4%), and stroke of undetermined aetiology (40%, 44%). Sixty-three percent of the patients from the CHUA and 42% of the patients from the SDB were older than 70 years. Cardioembolic strokes were more prevalent in patients older than 70 years in both series. Untreated hypertension was more frequent in the SDB (SDB = 31% vs CHUA = 10%). The analysis of other databases shows that the prevalence of cardioembolic stroke is increasing worldwide. CONCLUSIONS: Our data show that the prevalence of lacunar strokes is decreasing worldwide whereas cardioembolic strokes are increasingly more frequent in both our hospital and other series compared to the SDB. These differences may be explained by population ageing and the improvements in management of hypertension and detection of cardioembolic arrhythmias in stroke units.

[Ultrasound study of the vagal nerve as a diagnostic tool in Guillain-Barre syndrome]. / Estudio ultrasonografico del nervio vago como herramienta diagnostica en el sindrome de Guillain-Barre.

TITLE: Estudio ultrasonografico del nervio vago como herramienta diagnostica en el sindrome de Guillain-Barre.

[Anterior circulation embolic stroke secondary to thrombotic occlusion of the brachiocephalic trunk: the usefulness of neurosonological studies]. / Ictus embolico de circulacion anterior secundario a una oclusion trombotica del tronco braquiocefalico: utilidad del estudio neurosonologico.

INTRODUCTION. Atherosclerotic occlusion of the brachiocephalic trunk (CBT) is a rare clinical entity and its presentation in the form of arterio-arterial embolism is uncommon. Early identification of patients with CBT occlusion may have important therapeutic implications. CASE REPORT. A man aged 49 presents with sudden onset symptoms involving the territory of the right middle cerebral artery. Emergent transcranial doppler evaluation showed a flow pattern of proximal right M1 occlusion. After intravenous recombinant tissue plasminogen activator administration, partial recanalization of the vessel was found and the patient improved clinically. Cervical and transcranial duplex sonography demonstrated an occlusion in CBT, which was later confirmed on CT angiography and digital angiography of supraaortic vessels. After aorto-innominate bypass, pathological analysis confirmed the atherosclerotic origin. CONCLUSIONS. The most common clinical presentation of CBT occlusion are transient ischemic symptoms related to steal phenomenon in the vertebro-basilar territory. Symptoms of carotid circulation stroke usually result from arterio-arterial embolic mechanism. Early recognition is important for its therapeutic implications, therefore thrombolytic therapy should be indicated. Neurosonologic study allows rapid and reliable examination on hemodynamic status and the presence of distal embolic phenomena.

[Intravenous thrombolytic treatment in acute ischemic stroke: initial results in the Complejo Hospitalario Universitario de Albacete]. / Administración de tratamiento trombolítico intravenosoen el ictus isquémico en fase aguda: resultados enel Complejo Hospitalario Universitario de Albacete.

AIM: To analyze the safety profile and clinical outcome of patients with acute cerebral ischemia who received open treatment with tissue plasminogen activator (rt-PA) in a hospital without previous experience. PATIENTS AND METHODS: This prospective and observational study were realized from January 2004 to January 2007. A total of 1,704 consecutive patients with ischemic stroke were attended. 72 of them (4.2%) were treated with rt-PA within 3 hours from the symptoms onset. We analyzed age, vascular risk factors, initial and 24 hours neurological state by the National Institute of Health Stroke Scale (NIHSS), incidence of intracerebral hemorrhage and mortality and independence at 90 days. Patients were treated by neurologist and stroke monitoring was performed in the emergency area. RESULTS: Baseline median NIHSS was 16. At 24 hours, 53% of patients had improved = or > 4 points in the NIHSS and 33% showed = or > 10 points improvement or total recovery. The median time from stroke onset to rt-PA treatment was 160 minutes. Symptomatic intracerebral hemorrhage occurred in two patients (2.7%). Overall mortality at 90 days was 9.7%, but was due to hemorrhagic brain complications only in one case. At three months, 51% of patients were independent according to the modified Rankin scale. CONCLUSIONS: Treatment of acute ischemic stroke within three hours with intravenous rt-PA is safe and is associated with favorable outcome when it is applied by neurologists following approved protocols even in hospitals without previous experience.

[Infection by Epstein-Barr virus and multiple sclerosis]. / Infección por virus de Epstein-Barr y esclerosis múltiple.

INTRODUCTION: Multiple sclerosis is the most important disabling neurological disease in young adulthood in our environment. However, its etiology remains unknown. It has been proposed that multiple sclerosis is caused by an interaction of genetic and environmental factors. In particular, Epstein-Barr virus infection could play a fundamental role in the pathophysiology of multiple sclerosis. METHODS: We have reviewed the most recent and important bibliography, both from epidemiologic and basic research studies, dealing with the possible association between Epstein-Barr virus infection and multiple sclerosis. RESULTS: Retrospective and prospective epidemiologic studies suggest a direct association between Epstein-Barr virus infection and the risk of multiple sclerosis. Several physiopathologic mechanisms, including molecular mimicry and bystander activation, could be responsible for this association. CONCLUSIONS: Based on the published evidence, Epstein-Barr virus infection can be considered to have a causal role in the etiology of multiple sclerosis. Further research should be conducted to elucidate the mechanisms underlying this association and to assess its potential for multiple sclerosis prevention and treatment.