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The prognostic significance of postcontrast enhancement of intracranial atheromatous plaque is uncertain. Prospective, long-term follow-up studies in Caucasians, using a multicenter design, are lacking. We aimed to evaluate whether this radiological sign predicts long-term new stroke in symptomatic and asymptomatic intracranial atherosclerotic disease (ICAD) patients.This was a prospective, observational, longitudinal, multicenter study. We included a symptomatic and an asymptomatic cohort of ICAD patients that underwent 3T MRI including high-resolution sequences focused on the atheromatous plaque. We evaluated grade of stenosis, plaque characteristics, and gadolinium enhancement ratio (postcontrast plaque signal/postcontrast corpus callosum signal). The occurrence of new events was evaluated at 3, 6, 9, and 12 months and annually thereafter. The association between plaque characteristics and new stroke was studied using Cox multiple regression survival analysis and Kaplan-Meier curves.Forty-eight symptomatic and 13 asymptomatic patients were included. During 56.3 ± 16.9 months, 11 patients (18%) suffered a new event (seven ischemic, two hemorrhagic, and two transient ischemic attacks). A receiver operating characteristic curve identified an enhancement ratio of1.77 to predict a new event. In a multivariable Cox regression, postcontrast enhancement ratio1.77 (hazard ratio [HR]= 3.632; 95% confidence interval [CI], 1.082-12.101) and cerebral microbleeds (HR = 5.244; 95% CI, 1.476-18.629) were independent predictors of future strokes. Patients with a plaque enhancement ratio1.77 had a lower survival free of events (p .05).High intracranial postcontrast enhancement is a long-term predictor of new stroke in ICAD patients. Further studies are needed to elucidate whether postcontrast enhancement reflects inflammatory activity of intracranial atheromatous plaque.

[Background] Anosmia is common in Coronavirus disease 2019, but its impact on prognosis is unknown. We analysed whether anosmia predicts in-hospital mortality; and if patients with anosmia have a different clinical presentation, inflammatory response, or disease severity., [Methods] Retrospective cohort study including all consecutive hospitalized patients with confirmed Covid-19 from March 8th to April 11th, 2020. We determined all-cause mortality and need of intensive care unit (ICU) admission. We registered the first and worst laboratory parameters. Statistical analysis was done by multivariate logistic and linear regression., [Results] We included 576 patients, 43.3% female, and aged 67.2 years in mean. Anosmia was present in 146 (25.3%) patients. Patients with anosmia were more frequently females, younger and less disabled and had less frequently hypertension, diabetes, smoking habit, cardiac and neurological comorbidities. Anosmia was independently associated with lower mortality (OR: 0.180, 95% CI: 0.069–0.472) and ICU admission (OR: 0.438, 95% CI: 0.229–0.838, p = 0.013). In the multivariate analysis, patients with anosmia had a higher frequency of cough (OR: 1.96, 95%CI: 1.18–3.28), headache (OR: 2.58, 95% CI: 1.66–4.03), and myalgia (OR: 1.74, 95% CI: 1.12–2.71). They had higher adjusted values of hemoglobin (+0.87, 95% CI: 0.40–1.34), lymphocytes (+849.24, 95% CI: 157.45–1541.04), glomerular filtration rate (+6.42, 95% CI: 2.14–10.71), and lower D-dimer (−4886.52, 95% CI: −8655.29-(−1117.75)), and C-reactive protein (−24.92, 95% CI: −47.35-(−2.48))., [Conclusions] Hospitalized Covid-19 patients with anosmia had a lower adjusted mortality rate and less severe course of the disease. This could be related to a distinct clinical presentation and a different inflammatory response.

Introduction: Headache is one of the most frequent neurologic manifestations in COVID-19. We aimed to analyze which symptoms and laboratory abnormalities were associated with the presence of headache and to evaluate if patients with headache had a higher adjusted in-hospital risk of mortality. Methods: Retrospective cohort study. We included all consecutive patients admitted to the Hospital with confirmed SARS-CoV-2 infection between March 8th and April 11th, 2020. We collected demographic data, clinical variables and laboratory abnormalities. We used multivariate regression analysis. Results: During the study period, 576 patients were included, aged 67.2 (SD: 14.7), and 250/576 (43.3%) being female. Presence of headache was described by 137 (23.7%) patients. The all-cause in-hospital mortality rate was 127/576 (20.0%). In the multivariate analysis, patients with headache had a lower risk of mortality (OR: 0.39, 95% CI: 0.17–0.88, p = 0.007). After adjusting for multiple comparisons in a multivariate analysis, variables that were independently associated with a higher odds of having headache in COVID-19 patients were anosmia, myalgia, female sex and fever; variables that were associated with a lower odds of having headache were younger age, lower score on modified Rankin scale, and, regarding laboratory variables on admission, increased C-reactive protein, abnormal platelet values, lymphopenia and increased D-dimer. Conclusion: Headache is a frequent symptom in COVID-19 patients and its presence is an independent predictor of lower risk of mortality in COVID-19 hospitalized patients.

Introduction: Coronavirus disease 2019 (Covid-19) might present neurologic symptoms. We aimed to evaluate the frequency and type of neurologic symptoms in patients with Covid-19 at the moment of emergency department (ED) visit, and their impact in the prognosis. Methods: Retrospective cohort study including all consecutive confirmed Covid-19 cases that were hospitalized between March 8th and April 11th, 2020. We compared, in patients with and without neurological symptoms on admission, demographic, clinical presentation, and frequency and type of abnormal laboratory values. We analyzed the variables that were associated with in-hospital all-cause mortality by Cox-regression log rank test. Results: We included 576 patients, 250 (43·3%) female, aged 67·2 years in mean. At the moment of ED visit, 320 (55·6%) patients described neurologic symptoms, including anosmia in 146 (25·3%), myalgia in 139 (24·1%), headache in 137 (23·8%) and altered mental status in 98 (17·0%). In those patients, neurologic symptoms started the first day of symptoms in 198 (54·2%) cases. Patients with neurologic symptoms presented later to the ED (7·9 vs. 6·6 days, p=0·019). In patients with neurologic symptoms, only four (0·6%) cases had not typical Covid-19 general symptoms and only six (1·9%) had a normal laboratory results at the moment of ED presentation, for a sensitivity of 98·7% (95% confidence interval (CI): 96·6-99·6%) and 98·1% (95% CI: 95·7-99·2%), respectively. In the multivariate Cox-regression analysis of mortality predictors, anosmia (HR: 0·358, 95%CI: 0·140-0·916) and altered mental status (HR: 1·867, 95%CI: 1·162-3·001) remained statistically significant. Conclusion: Neurologic symptoms were the most frequent extrapulmonary symptoms. They were present in half of the patients with Covid-19 at the time of the ED visit. In almost all of the cases, typical Covid-19 general symptoms and/or laboratory abnormalities were present. The presence of neurologic symptoms at the moment of ED presentation was an independent predictor of mortality. Funding Statement: The present study did not have any specific source of funding. Declaration of Interests: Authors declare not to have any conflict of interest. Ethics Approval Statement: The study was approved by the local ethics review board (PI-20-1751), which waived the need of written informed consent.

Partially presented as a Poster at the LXV Meeting of Spanish Neurology Society, Barcelona, November 2013.

Background: Identification of novel prognostic factors associated with the risk of stroke recurrence in patients with symptomatic intracranial atherosclerosis (ICAS) is needed. Intraplaque post-contrast enhancement (PCE) in high-resolution MRI (HRMRI) has been proposed as a potential marker of plaque activity. We aimed to study intraplaque PCE prevalence, temporal evolution and their associated factors, in patients with symptomatic ICAS. Methods: We studied 10 consecutive patients with symptomatic ICAS who underwent HRMRI within the first 15 days after stroke onset and a control HRMRI three months thereafter. At each timepoint, symptomatic plaque and wall area were measured in T2 sequences, whereas plaque and wall signal intensity were measured with and without gadolinium contrast in T1 sequence. All HRMRI data were post-processed by two independent readers using Osirix imaging software. Results: Baseline HRMRI showed PCE in 70% of patients. Among baseline variables, a significant correlation was found between T1 spontaneous intraplaque intensity and postcontrast intraplaque intensity. We could not observe a homogeneous temporal evolution of postcontrast intraplaque intensity during the first 3 months, with half of the patients showing a decrease and the remaining having stable or increased values. No significant associations with intraplaque intensity variation were found. Conclusion: Intraplaque PCE was found in the majority (70%) of symptomatic intracranial atherosclerotic plaques during the acute phase. Interestingly, spontaneous and postcontrast intraplaque T1 signal intensities were highly correlated. Intraplaque PCE declined during the first three months in half of the patients.

Background OnabotulinumtoxinA (OnabotA) is effective in Chronic Migraine (CM) during first year of treatment and longer. In real clinical setting, CM patients with acute Medication Overuse (MO) or concurrently receiving oral preventatives are treated with OnabotA. We aim to assess evolution of CM patients beyond first year on OnabotA. Methods Data were retrospectively collected in three headache units. We analyzed cases who had received at least five sessions of OnabotA according to PREEMPT protocol. We continued OnabotA therapy when a reduction of number of headache days of at least 30% was achieved. Results We included 115 patients (98 females, 17 males) who completed 7.6 ± 2.3 (5–13) OnabotA procedures. Previously they had not responded to topiramate and, at least, one other preventative. Age at inclusion was 45.3 ± 12 (14–74) years, and latency between CM onset and OnabotA therapy was 43.1 ± 38.2 (6–166) months. At first OnabotA session 92 patients (80%) fulfilled MO criteria and 107 (93%) received a concurrent oral preventative. In 42 cases (36.5%) OnabotA dose was increased over 155 units. After first year in 57 out of 92 patients (61.9%) MO was discontinued. Among those receiving preventatives, in 52 out of 107 they were retired (48.6%). In 22 cases (19.1%) OnabotA administration was delayed to the fourth or fifth month and in 12 (10.4%) it was temporally stopped. Finally, in 18 patients (15.7%) OnabotA was discontinued due to lack of efficacy beyond first year of treatment. Conclusion Our results suggest that discontinuation of acute medication overuse and oral preventive therapies are achievable objectives in long-term using of OnabotA in CM patients.

Es habitual que los ataques de dolor en la migrana se acompanen de sintomas vegetativos, pero tampoco es infrecuente que asocien sintomas autonomicos que nos obligaran a hacer un diagnostico diferencial con las cefaleas trigeminoautonomicas. Recientemente, un grupo espa­nol ha propuesto una escala para valorar y cuantificar los sintomas autonomicos que acompanan la migrana [1]. Mujer de 58 anos, con antecedentes personales de hipertension arterial e hiperlipidemia familiar, asi como antiguo tabaquismo. Presentaba desde su juventud episodios infrecuentes (entre dos y tres al mes), consistentes en una cefalea periocular, generalmente lateralizada hacia la izquierda, de caracter pulsatil, de moderada-gran intensidad, y acompanada de fotofobia y sonofobia. Como desencadenante destacaba el ejercicio fisico. La mayoria de los ataques, en especial los de mayor intensidad, se asociaban a edema palpebral y lagrimeo, en ambos casos bilaterales y, sobre todo, a una especialmente llamativa congestion nasal. Sin tratamiento, la duracion tanto de dolor como de los sintomas acompanantes podia ser hasta de 72 horas. La respuesta a analgesicos o antiinflamatorios era escasa y, en cambio, el uso de sumatriptan conseguia resolver el cuadro en unas dos horas en la mayoria de los ataques. La paciente, que desempena un trabajo cara al publico, se ausentaba de el en los ataques mas prolongados, sobre todo debido a la aparatosidad de la tumefaccion nasal. Meses antes de acudir a la consulta sufrio una cardiopatia isquemica con infarto inferior por oclusion trombotica de la arteria coronaria derecha revascularizada con stent convencional. Fue remitida a neurologia buscando una alternativa al tratamiento sintomatico con triptanes, contraindicados tras la cardiopatia isquemica. Al ser atendida por primera vez por nosotros, sufria unos dos ataques mensuales como los descritos, si bien prolongados e invalidantes por la escasa respuesta a antiinflamatorios. El uso de bisoprolol en el contexto de su tratamiento cardiologico no habia reducido esa frecuencia. Las exploraciones neurologica y otorrinolaringologica basales fueron rigurosamente normales. Un estudio de resonancia magnetica cerebral no mostro alteracion alguna. Propusimos como tratamiento preventivo la administracion de topiramato en dosis bajas (50 mg/dia en toma unica nocturna), lo que dio lugar a una importante disminucion del numero de ataques de migrana, incluyendo una menor intensidad en los que se producian. Los sintomas autonomicos craneales descritos en los criterios diagnosticos de la migrana son lagrimeo, inyeccion conjuntival, edema palpebral, pletora aural y congestion nasal [1]. La prevalencia de estos sintomas oscila entre el 27-37% en estudios de base poblacional y alcanza hasta un 50% en registros de consultas de neurologia [1-3]. En cuanto a sintomas autonomicos nasales, se describen en el 20% de pacientes con migrana cronica, principalmente rinorrea y congestion nasal con intensidad leve [1]. Los sintomas autonomicos asociados a la migrana tienen unas caracteristicas especiales. A diferencia de lo descrito en las cefaleas trigeminoautonomicas, aparecen generalmente de forma bilateral y son menos intensos. Finalmente, no se relacionan con la localizacion del dolor y su aparicion es menos constante [4]. En las series publicadas hasta el momento, se senala que los sintomas autonomicos se producen con mayor frecuencia en ataques de migrana de mayor intensidad [5,6] y duracion [3], asi como en las migranas de larga evolucion [3]. Nuestro caso presenta estas mismas caracteristicas. Analizamos brevemente, buscando la explicacion etiopatogena de la presencia de sintomas autonomicos en la migrana, la estructura del sistema nervioso autonomo en el craneo. El ganglio esfenopalatino es el ganglio parasimpatico extracraneal de mayor tamano, que recibe a su vez fibras sensitivas y simpaticas sin que estas realicen sinapsis en el. En cuanto a las fibras parasimpaticas, las que tienen su origen en el nucleo salivatorio superior de la protuberancia inervan las arterias extra/intracraneales, la glandula lagrimal, la mucosa nasal, la conjuntiva y el musculo de Muller, mientras que las originadas en el plexo carotideo inervan la glandula lagrimal y nasal, y la mucosa palatina. El reflejo trigeminoautonomico parasimpatico est­a constituido por conexiones en el tronco del encefalo entre las aferencias trigeminales y las eferencias parasimpaticas vehiculadas por el nervio facial que realizan sinapsis en el ganglio esfenopalatino [7]. Centrandonos en la aparicion de los sintomas autonomicos en un ataque de migrana, el primer paso seria la activacion del sistema trigemino vascular, tras un estimulo nociceptivo sobre las terminaciones nerviosas del nervio trigemino. Esta informacion nociceptiva viaja hasta el nucleo salivatorio superior, el que estimula la liberacion de neurotransmisores como el peptido relacionado con el gen de la calcitonina y el oxido nitrico. Por otra parte, la via eferente del reflejo produce la liberacion del peptido intestinal vasoactivo [5]. Todo ello produce una dilatacion de los vasos intracraneales, una extravasacion de las proteinas del plasma y una liberacion local de moleculas inflamatorias, que activan los nociceptores de las meninges [7]. El sistema parasimpatico contiene y libera un gran numero de transmisores y sustancias neuromoduladoras, como la acetilcolina, y varios peptidos, como la histidina-metionina, polipeptido activador de la adenilato ciclasa hipofisaria, peptidos intestinales vasoactivos que contribuyen a regular el tono del lecho cerebrovascular y la hemodinamica cerebral. Su activacion y, por tanto, la liberacion de los neurotransmisores y peptidos previamente mencionados favorecen la vasodilatacion y la inflamacion leptomeningea que, al menos en parte, son responsables de algunos sintomas, como el lagrimeo, el enrojecimiento conjuntival, la rinorrea y la congestion nasal [5]. Aunque la causa de la persistencia del dolor en la migrana es desconocida, se piensa que las vias del dolor se hipersensibilizan debido a los episodios repetidos de activacion de las dos vias, la sensorial y la parasimpatica, correspondientes al reflejo trigeminoautonomico [8]; ello explicaria la presencia de sintomas autonomicos, sobre todo en los ataques prolongados de migrana. Por otra parte, la sobreactivacion del reflejo trigeminal produce el reclutamiento de los receptores perifericos neurovasculares (5-HT1B/1D), diana en el tratamiento sintomatico de la migrana. Este hecho podria explicar la buena respuesta al tratamiento con triptanes de los ataques con sintomas autonomicos [9], como observamos en nuestra paciente. En nuestro caso, los sintomas autonomicos mas llamativos se producen en la nariz. Recientemente se han observado en pacientes migranosos hiperemia de la mucosa nasal, hipertrofia del cornete inferior y aumento de resistencia de la mucosa nasal [10]. Debemos, pues, tomar en consideracion la frecuencia de sintomas autonomicos acompanando a la migrana, en ocasiones de forma tan aparatosa e invalidante como ocurrio en esta descripcion clinica. Suele ser conveniente realizar el diagnostico diferencial con las cefaleas trigeminoautonomicas; las caracteristicas del dolor y la bilateralidad habitual de estos sintomas cuando acompanan a la migrana nos ayudan en esta tarea.

Cutaneous manifestations of migraine are infrequent and their spectrum is reduced to the red ear syndrome (RES) and eyelid disorders. We report a case of a 26-year-old woman with migraine accompanied by extensive erythema, which involved right ear and cheek and left hemithorax. She fulfilled proposed criteria of RES. We started preventive therapy with a significant response. This is the first description in the literature of an erythema accompanying migraine attacks broadly exceeding the ear.

Background and Objective: Acute ischemic stroke (AIS) associated with tandem extracranial internal carotid artery (EICA) - middle cerebral artery (MCA) occlusion is burdened with a poor clinical outcome. The recanalization rate of extracranial ICA occlusion after i.v. thrombolysis and its prognostic significance in this group of patients remain largely unknown. Methods: Retrospective analysis of a prospectively collected database including consecutive AIS patients treated with i.v. thrombolysis. All patients underwent urgent assessment of extracranial and intracranial large arteries with either computed tomography angiography (CTA) or echo-Doppler ultrasound to document an acute EICA-MCA tandem occlusion prior to thrombolysis. EICA was monitored by control carotid ultrasound and/or CTA in order to detect transition from occlusion to relevant stenosis. Outcome variables: carotid revascularization, in-hospital mortality, Rankin 0-2 at three months, and infarct volume. Results: From January 2008 to December 2013, 606 AIS patients received i.v. thrombolysis, of whom 53 (9%) had a documented EICA-MCA tandem occlusion. Four of them died within first 24 hours and EICA could not be monitored. Occluded EICA evolved towards a severe stenosis in 14/49 (29%) after thrombolysis. Angiographic confirmation was obtained in 11 of them, who underwent carotid endarterectomy. EICA recanalization was more frequent among active smokers and was associated with carotid revascularization (79% vs. 0%, p Conclusion: Around 30% of AIS patients with tandem EICA-MCA occlusion treated with i.v. thrombolysis experience transition from initially occluded to severely stenosed EICA that can be rescued for revascularization. This evolution is associated with a lower mortality and smaller infarct volume.