[Thrombosis with Thrombocytopenia Syndrome following adenovirus vector-based vaccines to prevent COVID-19: epidemiology and clinical presentation in Spain]. / Síndrome de Trombosis con Trombocitopenia asociado a vacunas de adenovirus frente a la COVID-19: epidemiología y presentación clínica de la serie española.

BACKGROUND: We describe the epidemiological and clinical characteristics of thrombosis with thrombocytopenia syndrome (TTS) cases reported in Spain. METHODS: We included all venous or arterial thrombosis with thrombocytopenia following adenovirus vector-based vaccines (AstraZeneca or Janssen) to prevent COVID-19 disease between February 1st and September 26th, 2021. We describe the crude rate and the standardized morbidity ratio. We assessed the predictors of mortality. RESULTS: Sixty-one cases were reported and 45 fulfilled eligibility criteria, 82% women. The crude TTS rate was 4/1,000,000 doses and 14-15/1,000,000 doses between 30-49 years. The number of observed cases of cerebral venous thrombosis was 6-18 higher than the expected in patients younger than 49 years. Symptoms started 10 (interquartile range (IQR): 7-14) days after vaccination. Eighty percent (95% confidence interval (CI): 65-90%) had thrombocytopenia at the time of the emergency department visit, and 65% (95% CI: 49-78%) had D-dimer >2000 ng/mL. Patients had multiple location thrombosis in 36% and fatal outcome in 24% cases. A platelet nadir <50,000 /µL (odds ratio (OR): 7.4; CI 95%: 1.2-47.5) and intracranial hemorrhage (OR: 7.9; IC95%: 1.3-47.0) were associated with fatal outcome. CONCLUSION: TTS must be suspected in patients with symptoms 10 days after vaccination and thrombocytopenia and/or D-dimer increase.

MAB-MIG: registry of the spanish neurological society of erenumab for migraine prevention.

BACKGROUND: Erenumab was approved in Europe for migraine prevention in patients with ≥ 4 monthly migraine days (MMDs). In Spain, Novartis started a personalized managed access program, which allowed free access to erenumab before official reimbursement. The Spanish Neurological Society started a prospective registry to evaluate real-world effectiveness and tolerability, and all Spanish headache experts were invited to participate. We present their first results. METHODS: Patients fulfilled the ICHD-3 criteria for migraine and had ≥ 4 MMDs. Sociodemographic and clinical data were registered as well as MMDs, monthly headache days, MHDs, prior and concomitant preventive treatment, medication overuse headache (MOH), migraine evolution, adverse events, and patient-reported outcomes (PROs): headache impact test (HIT-6), migraine disability assessment questionnaire (MIDAS), and patient global improvement change (PGIC). A > 50% reduction of MMDs after 12 weeks was considered as a response. RESULTS: We included 210 patients (female 86.7%, mean age 46.4 years old) from 22 Spanish hospitals from February 2019 to June 2020. Most patients (89.5%) suffered from chronic migraine with a mean evolution of 8.6 years. MOH was present in 70% of patients, and 17.1% had migraine with aura. Patients had failed a mean of 7.8 preventive treatments at baseline (botulinum toxin type A-BoNT/A-had been used by 95.2% of patients). Most patients (67.6%) started with erenumab 70 mg. Sixty-one percent of patients were also simultaneously taking oral preventive drugs and 27.6% were getting simultaneous BoNT/A. Responder rate was 37.1% and the mean reduction of MMDs and MHDs was -6.28 and -8.6, respectively. Changes in PROs were: MIDAS: -35 points, HIT-6: -11.6 points, PIGC: 4.7 points. Predictors of good response were prior HIT-6 score < 80 points (p = 0.01), ≤ 5 prior preventive treatment failures (p = 0.026), absence of MOH (p = 0.039), and simultaneous BoNT/A treatment (p < 0.001). Twenty percent of patients had an adverse event, but only two of them were severe (0.9%), which led to treatment discontinuation. Mild constipation was the most frequent adverse event (8.1%). CONCLUSIONS: In real-life, in a personalized managed access program, erenumab shows a good effectiveness profile and an excellent tolerability in migraine prevention in our cohort of refractory patients.

Seizures and COVID-19: Results from the Spanish Society of Neurology's COVID-19 registry.

We describea series of patients with COVID-19 who presented with seizures, reported in the Spanish Society of Neurology's COVID-19 Registry. This observational, descriptive,multicentre, registry-based study includes patients with confirmed COVID-19 who experienced seizures during active infection.Wedescribe theclinicalpresentation of COVID-19,seizures,and resultsof complementary tests.Wealsodescribe the suspectedaetiologyof the seizures. Of 232 reported cases, 26 (11.2%) presented with seizures;7 of these patients (26.9%) had prior history of epilepsy, whereas the remaining 19 (73.1%) had no history of seizures.In most cases, seizures presented on days 0 and 7 after onset of COVID-19. By seizure type, 8 patients (30.7%) presentedgeneralised tonic-clonic seizures, 7 (26.9%) status epilepticus, 8 (30.7%) focal impaired-awareness seizures, and 4 (11.7%) secondary generalised seizures.Six patients (23.1%) also presented other neurological symptoms, includingaltered mental status and decreased level of consciousness. Predisposing factors for seizures (eg, dementia, tumour, cerebrovascular disease) were observed in 10 of the 19 patients with no prior history of epilepsy (52.6%). Patients with COVID-19 may present with seizures over the course of the disease,either alone or in the context of encephalopathy.Seizures may present in patients with no prior history of epilepsy; however, most of these patients present predisposing factors.

Neurological presentations of COVID-19: Findings from the Spanish Society of Neurology neuroCOVID-19 registry.

OBJECTIVE: We report the findings from the Spanish Society of Neurology's NeuroCOVID-19 Registry. METHODS: We performed a multicentre study of patients with neurological manifestations of COVID-19. Participating physicians reported demographic, clinical, and paraclinical data and judged the involvement of COVID-19 in causing neurological symptoms. RESULTS: A total of 233 cases were submitted, including 74 different combinations of manifestations. The most frequently reported were stroke (27%), neuromuscular symptoms (23.6%), altered mental status (23.6%), anosmia (17.6%), headache (12.9%), and seizures (11.6%). The mean age of patients was 61.1 years, with 42.1% being women; a higher proportion of women was recorded among patients with altered mental status, anosmia, and headache. The onset of symptoms differed within categories. Onset of anosmia occurred a mean (standard deviation) of 2.9 (2.5) days after the first general symptom, whereas neuromuscular symptoms appeared after 13.9 (10.1) days. Neurological symptoms were persistent in 33% of patients. General symptoms were present in 97.7% of patients, and results from general laboratory studies were abnormal in 99.4% of patients. Cerebrospinal fluid analysis findings were abnormal in 62.7% of the cases in which this test was performed (n = 51), but positive results for SARS-CoV-2 were only found in one case. CONCLUSIONS: The neurological manifestations of COVID-19 are diverse. Anosmia, myalgia, and headache occur earlier in the course of the disease. Altered mental status, neuromuscular symptoms, and stroke are associated with greater severity. COVID-19 must be incorporated into most clinical and radiological differential diagnoses. COVID-19 may cause persistent and disabling neurological symptoms.

[Catastrophic headache]. / Cefaleas catastróficas.

Headache is like a poker player that often hides an ace up its sleeve. Sometimes because of the cruelty of the cause, other times because of misfortune and still others because of clinician error or the various steps involved in accessing healthcare, there are processes that manifest as isolated events or mainly as headache and whose consequences may be catastrophic. This article provides a brief but committed analysis of some of the main causes of catastrophic headache and aims to increase awareness of the importance of headache as a reason for consultation and of the thin line between innocuous and serious processes, between protocol and art, and between knowing too little and knowing too much.

An Online Observational Study of Patients With Olfactory and Gustory Alterations Secondary to SARS-CoV-2 Infection.

Introduction: Since the beginning of the Covid-19 epidemic produced by SARS2-Cov virus, olfactory alterations have been observed at a greater frequency than in other coronavirus epidemics. While olfactory alterations may be observed in patients with rhinovirus, influenza virus, or parainfluenza virus infection, they are typically explained by nasal obstruction with mucus or direct epithelial damage; in the case of SARS-CoV-2, olfactory alterations may present without nasal congestion with mucus. We performed a study of patients presenting olfactory/gustatory alterations in the context of SARS-CoV-2 infection in order to contribute to the understanding of this phenomenon. Material and Methods: We performed a descriptive, cross-sectional, observational study of the clinical characteristics of olfactory/gustatory alterations using a self-administered, anonymous online questionnaire. Results: A total of 909 patients with SARS-CoV-2 infection and olfactory/gustatory alterations responded to the questionnaire in the 4-day data collection period; 824 cases (90.65%) reported simultaneous olfactory and gustatory involvement. Patients' responses to the questionnaire revealed ageusia (581, 64.1% of respondents), hypogeusia (256, 28.2%), dysgeusia (22, 2.4%), anosmia (752 82.8%), hyposmia (142, 15.6%), and dysosmia (8, 0.9%). Fifty-four percent (489) did not report concomitant nasal congestion or mucus. Conclusion: Olfactory alterations are frequent in patients with SARS-CoV-2 infection and is only associated with nasal congestion in half of the cases.

Neurological Comorbidity Is a Predictor of Death in Covid-19 Disease: A Cohort Study on 576 Patients.

Introduction: Prognosis of Coronavirus disease 2019 (Covid-19) patients with vascular risk factors, and certain comorbidities is worse. The impact of chronic neurological disorders (CND) on prognosis is unclear. We evaluated if the presence of CND in Covid-19 patients is a predictor of a higher in-hospital mortality. As secondary endpoints, we analyzed the association between CND, Covid-19 severity, and laboratory abnormalities during admission. Methods: Retrospective cohort study that included all the consecutive hospitalized patients with confirmed Covid-19 disease from March 8th to April 11th, 2020. The study setting was Hospital Clínico, tertiary academic hospital from Valladolid. CND was defined as those neurological conditions causing permanent disability. We assessed demography, clinical variables, Covid-19 severity, laboratory parameters and outcome. The primary endpoint was in-hospital all-cause mortality, evaluated by multivariate cox-regression log rank test. We analyzed the association between CND, covid-19 severity and laboratory abnormalities. Results: We included 576 patients, 43.3% female, aged 67.2 years in mean. CND were present in 105 (18.3%) patients. Patients with CND were older, more disabled, had more vascular risk factors and comorbidities and fewer clinical symptoms of Covid-19. They presented 1.43 days earlier to the emergency department. Need of ventilation support was similar. Presence of CND was an independent predictor of death (HR 2.129, 95% CI: 1.382-3.280) but not a severer Covid-19 disease (OR: 1.75, 95% CI: 0.970-3.158). Frequency of laboratory abnormalities was similar, except for procalcitonin and INR. Conclusions: The presence of CND is an independent predictor of mortality in hospitalized Covid-19 patients. That was not explained neither by a worse immune response to Covid-19 nor by differences in the level of care received by patients with CND.

[Antidepressant drugs in the treatment of tension-type headache]. / Fármacos antidepresivos en el tratamiento de la cefalea tensional.

Tension-type headache is the most common form of headache. Eighty percent of cases occur before 40 years of age. A wide variety of antidepressants have been used to treat it. Tricyclics are the only antidepressants that have demonstrated their effectiveness in treating chronic tension-type headache, amitriptyline being the drug of choice. Selective serotonin reuptake inhibitors and other families of antidepressants have not shown conclusive results yet. The present study is a review of the scientific evidence available on antidepressants for treatment of this kind of headache.

Hospital Admissions in People With Alzheimer's Disease or Senile Dementia According to Type 2 Diabetes Status: An Observational 10-Year Study.

We aimed to describe admission rates and outcomes of hospitalized people with Alzheimer's disease (AD) or senile dementia stratified by type 2 diabetes (T2D) in Spain, 2004 to 2013 (N = 541 858, 143 501 [26.5%] of whom had T2D). We excluded alternative causes of dementia. Hospitalization rates were higher in people with T2D (130.5 vs 91.5 cases/105 people). People older than 84 years and comorbidity increased over time. Crude inhospital mortality (IHM) decreased over time both in people with and without T2D (all P values <.001). Time trend analyses, 2004 to 2013, showed an overall adjusted incidence rate ratio (95% confidence interval [95% CI]) of hospitalization of 1.41 (1.40-1.42) for T2D (men, 1.32 [1.30-1.33]; women, 1.46 [1.45-1.48]). In logistic regression analyses, IHM decreased over time (odds ratio, OR [95% CI] = 0.97 [0.96-0.98]) and T2D was not associated with a higher IHM (OR [95% CI] = 0.99 [0.98-1.01]). In conclusion, admission rates were higher in patients with T2D. Inhospital mortality decreased over time. Diabetes did not predict IHM in patients with AD or senile dementia.

[Chronic migraine: definition, epidemiology, risk factors and treatment]. / Migraña crónica: definición, epidemiología, factores de riesgo y tratamiento.

INTRODUCTION: Chronic migraine is the most frequent complication of migraine. It is defined by the presence of headache on 15 or more days a month, of which at least eight must meet the criteria of migraine without aura for a minimum of three months. In addition they must not be due to medication abuse or attributable to any other cause. DEVELOPMENT: The prevalence of chronic migraine ranges between 1-3% of the population and its incidence has been estimated to be 2.5% per year. It produces from four to six times more disability, decreased productivity and disruption of quality of life than episodic migraine. The development of chronic migraine has been associated with both non-modifiable risk factors (being female, low socio-economic status and level of schooling) and modifiable risk factors (anxiety, depression, sleep apnoea/snoring, obesity, consumption of painkillers and caffeine). Patients with chronic migraine suffer from chronic pain, anxiety or depression two to three times more often than those with episodic migraine. Management requires identification and control of the risk factors that predispose patients to develop the condition, detoxification therapy in the event of abuse of analgesics, specific treatment for migraine attacks and preventive treatment. The effectiveness of the preventive drugs topiramate and Onabotulinumtoxin A in this complication of migraine has been proved in large-scale placebo-controlled clinical trials. CONCLUSIONS: Chronic migraine is a common condition that requires global management aimed at reducing the frequency of the attacks, lowering the associated disability and improving the patients' quality of life.

Triggers, symptoms, and treatment in two populations of migraneurs in Brazil and Spain. A cross-cultural study.

BACKGROUND AND AIM: Cultural variation in pain and headache presentation may exist. The objective of this study was to assess cross-cultural differences in the use of drugs commonly managed to treat and prevent migraine, and to analyze the awareness about symptoms and triggers between two populations of migraneurs in Brazil and Spain. METHODS: International cross-cultural study. Patients answered a socio-demographic questionnaire that included questions about trigger factors, and use of drugs to treat and prevent migraine attacks. RESULTS: 292 patients (mean age 34.6 years; 80% females) were included in the study. Most common identified triggers in Brazilian and Spanish patients were: food (30.5% vs 12.6%), sleep (56.7% vs 28.5%), odors (52.5% vs 9.3%), stress (73.1% vs 46.4%), and menstrual period (55.6% vs 38.1%), all p<0.01. Analgesics and anti-inflammatory drugs were the most commonly used drugs to treat migraine attacks. Brazilian migraneurs used less commonly triptans (16.3% vs 47%; p<0.0001). Prophylactic drugs were used less frequently in Brazil than in Spain (21.9% vs 52.9%; p<0.0001). Calcium-antagonists, tricyclic anti-depressives, beta-blockers, and anti-epileptic drugs were significantly more used in Spanish migraineurs (p<0.01). CONCLUSIONS: Brazilians migraneurs are more often undertreated for migraine, and underutilization of triptans and preventatives was observed.

Medicina de precisión: precisamente ahora / Precision Medicine: precisely now

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Crisis miasténica y síndrome de takotsubo: una relación no casual / Myasthenic crisis and Takotsubo syndrome: a non-chance relationship

Introducción. El síndrome de takotsubo (STT) es una rara entidad que simula un infarto agudo de miocardio. Asocia dolor precordial, elevación del segmento ST, ausencia de oclusión coronaria y deformación reversible ventricular izquierda por discinesia anteroapical que recuerda a un arte japonés de pescar pulpos (tako-tsubo). Se relaciona con estrés emocional y físico, y se piensa que está mediado por una liberación catecolaminérgica aguda. Caso clínico. Mujer de 83 años, hipertensa. Ingresó en la unidad coronaria con sospecha de síndrome coronario agudo e insuficiencia respiratoria, por lo que requirió ventilación mecánica. El ecocardiograma mostró disfunción ventricular grave con discinesia apical. El cateterismo cardíaco descartó enfermedad coronaria. La ventriculografía reveló una deformación ampulosa sistólica de los segmentos anterior y apical (STT). Se intentó retirar la ventilación sin éxito y se consultó con neurología. La anamnesis dirigida reveló un cuadro de meses de evolución de debilidad generalizada, disfagia y disnea progresivas. Un test de edrofonio fue positivo. El electromiograma de fibra aislada mostró jitter patológico. Los anticuerpos antirreceptor de acetilcolina fueron positivos. La paciente fue tratada con inmunoglobulinas, corticoides y piridostigmina. El ecocardiograma de control objetivó resolución del STT. Conclusiones. El STT debe contemplarse dentro de las complicaciones extraneurológicas de la crisis miasténica. El neurólogo debe tenerlo presente ante cualquier síntoma o signo de potencial origen cardíaco en la crisis miasténica y otros padecimientos neurocríticos (AU)

Introduction. Takotsubo syndrome (TTS) is a rare condition that mimics an acute myocardial infarction. It is associated with precordial pain, ST segment elevation, absence of coronary occlusion and reversible deformation of the left ventricle due to anteroapical dyskinesia that is reminiscent of a Japanese art of fishing octopuses (tako-tsubo). It is related with emotional and physical stress, and is thought to be mediated by an acute release of catecholamines. Case report. An 83-year-old woman with hypertension. She was admitted to the heart unit with a suspected acute coronary syndrome and respiratory failure, and thus required mechanical ventilation. An echocardiography scan showed severe ventricular dysfunction with apical dyskinesia. Cardiac catheterisation ruled out heart disease and a ventriculography scan revealed a bloated systolic deformation of the anterior and apical segments (TTS). Attempts to withdraw ventilation were unsuccessful and the neurology department was consulted. A directed medical history revealed that the patient had been suffering from generalised weakness, and progressive dysphagia and dyspnoea for several months. Results of an edrophonium test were positive. Single-fibre electromyography showed a pathological jitter and acetylcholine antireceptor antibodies were positive. The patient was treated with immunoglobulins, corticoids and pyridostigmine. A control echocardiogram showed resolution of the TTS. Conclusions. TTS must be considered within the extra-neurological complications arising from myasthenic crisis. The neurologist must take this into account when faced with any symptom or sign of a potentially cardiac origin in myasthenic crisis and other neurocritical conditions (AU)

Migraña crónica: definición, epidemiología, factores de riesgo y tratamiento / Chronic migraine: definition, epidemiology, risk factors and treatment

Introducción. La migraña crónica es la complicación más frecuente de la migraña. Se define por la presencia de cefalea 15 o más días al mes, de los que al menos ocho deben cumplir criterios de migraña sin aura durante al menos tres meses, en ausencia de abuso de medicación y no atribuibles a otra causa. Desarrollo. Su prevalencia oscila entre el 1-3% de la población, y su incidencia se ha estimado en un 2,5% anual. Producede cuatro a seis veces más discapacidad, disminución de la productividad y alteración de la calidad de vida que la migrañaepisódica. El desarrollo de migraña crónica se ha asociado con varios factores de riesgo no modificables (sexo femenino, estatus socioeconómico y nivel educativo bajos) y modificables (ansiedad, depresión, apnea del sueño/ronquido, obesidad,consumo de analgésicos y cafeína). Los pacientes con migraña crónica sufren dolor crónico, ansiedad o depresión con una frecuencia 2-3 veces superior a la migraña episódica. Su abordaje requiere la identificación y el manejo de los factores de riesgo que predisponen a su desarrollo, deshabituación de analgésicos cuando hay abuso, tratamiento específico de lascrisis de migraña y tratamiento preventivo. Entre los fármacos preventivos, el topiramato y la Onabotulinumtoxin A handemostrado, en grandes ensayos clínicos controlados frente a placebo, su eficacia en esta complicación de la migraña. Conclusiones. La migraña crónica es una entidad frecuente que requiere un manejo global cuyos objetivos son reducir la frecuencia de las crisis, la discapacidad asociada y mejorar la calidad de vida de los pacientes (AU)

Introduction. Chronic migraine is the most frequent complication of migraine. It is defined by the presence of headache on 15 or more days a month, of which at least eight must meet the criteria of migraine without aura for a minimum ofthree months. In addition they must not be due to medication abuse or attributable to any other cause.Development. The prevalence of chronic migraine ranges between 1-3% of the population and its incidence has been estimated to be 2.5% per year. It produces from four to six times more disability, decreased productivity and disruption of quality of life than episodic migraine. The development of chronic migraine has been associated with both non-modifiablerisk factors (being female, low socio-economic status and level of schooling) and modifiable risk factors (anxiety, depression, sleep apnoea/snoring, obesity, consumption of painkillers and caffeine). Patients with chronic migraine suffer from chronicpain, anxiety or depression two to three times more often than those with episodic migraine. Management requires identification and control of the risk factors that predispose patients to develop the condition, detoxification therapy in the event of abuse of analgesics, specific treatment for migraine attacks and preventive treatment. The effectiveness of the preventive drugs topiramate and Onabotulinumtoxin A in this complication of migraine has been proved in large-scaleplacebo-controlled clinical trials.Conclusions. Chronic migraine is a common condition that requires global management aimed at reducing the frequencyof the attacks, lowering the associated disability and improving the patients’ quality of life (AU)

Síndrome de hipotensión intracraneal espontánea: utilidad de los signos directos e indirectos de fuga del líquido cefalorraquídeo en la cisternografía isotópica / Spontaneous intracranial hypotension syndrome: usefulness of direct and indirect findings of cerebrospinal fluid leakage in isotope cisternography

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Cefaleas catastróficas / Catastrophic headache

El dolor de cabeza es un jugador de póquer que con frecuencia esconde un as bajo la manga. Unas veces por la crueldad de la causa, otras por el infortunio y otras tantas por la impericia del clínico o lo sinuoso del camino asistencial, hay procesos que se manifiestan de forma aislada o predominante por un dolor de cabeza cuyas consecuencias pueden ser catastróficas. Este trabajo presenta un somero pero comprometido análisis de algunos de los principales motivos de cefalea catastrófica y pretende sensibilizar al lector sobre la importancia del dolor de cabeza como motivo de consulta y la delgada línea que puede separar lo banal de lo grave, el protocolo del arte y saber poco de saber demasiado (AU)

Headache is like a poker player that often hides an ace up its sleeve. Sometimes because of the cruelty of the cause, other times because of misfortune and still others because of clinician error or the various steps involved in accessing healthcare, there are processes that manifest as isolated events or mainly as headache and whose consequences may be catastrophic. This article provides a brief but committed analysis of some of the main causes of catastrophic headache and aims to increase awareness of the importance of headache as a reason for consultation and of the thin line between innocuous and serious processes, between protocol and art, and between knowing too little and knowing too much (AU)