Effectiveness and safety of anti-CGRP monoclonal antibodies in patients over 65 years: a real-life multicentre analysis of 162 patients.

BACKGROUND: Anti-CGRP monoclonal antibodies have shown notable effectiveness and tolerability in migraine patients; however, data on their use in elderly patients is still lacking, as clinical trials have implicit age restrictions and real-world evidence is scarce. In this study, we aimed to describe the safety and effectiveness of erenumab, galcanezumab and fremanezumab in migraine patients over 65 years old in real-life. METHODS: In this observational real-life study, a retrospective analysis of prospectively collected data from 18 different headache units in Spain was performed. Migraine patients who started treatment with any anti-CGRP monoclonal antibody after the age of 65 years were included. Primary endpoints were reduction in monthly migraine days after 6 months of treatment and the presence of adverse effects. Secondary endpoints were reductions in headache and medication intake frequencies by months 3 and 6, response rates, changes in patient-reported outcomes and reasons for discontinuation. As a subanalysis, reduction in monthly migraine days and proportion of adverse effects were also compared among the three monoclonal antibodies. RESULTS: A total of 162 patients were included, median age 68 years (range 65-87), 74.1% women. 42% had dyslipidaemia, 40.3% hypertension, 8% diabetes, and 6.2% previous cardiovascular ischaemic disease. The reduction in monthly migraine days at month 6 was 10.1 ± 7.3 days. A total of 25.3% of patients presented adverse effects, all of them mild, with only two cases of blood pressure increase. Headache and medication intake frequencies were significantly reduced, and patient-reported outcomes were improved. The proportions of responders were 68%, 57%, 33% and 9% for reductions in monthly migraine days ≥ 30%, ≥ 50%, ≥ 75% and 100%, respectively. A total of 72.8% of patients continued with the treatment after 6 months. The reduction in migraine days was similar for the different anti-CGRP treatments, but fewer adverse effects were detected with fremanezumab (7.7%). CONCLUSIONS: Anti-CGRP mAbs are safe and effective treatments in migraine patients over 65 years old in real-life clinical practice.

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.

Histology of a cerebral hemorrhage: AVM as a seat of a metastatic choriocarcinoma.

INTRODUCTION: There are published cases of cerebral hemorrhage secondary to vascular alterations caused by choriocarcinoma metastases. However, it is extremely rare to find this type of bleeding secondary to an association of such a metastasis with a brain arteriovenous malformation (AVM). CLINICAL CASE: We present the case of a 19-year-old male who came to the Emergency Department complaining of intense headache of abrupt onset. His physical examination revealed a striking increase in size of the right testicle of tumoral origin. Chest X-ray evidenced metastasis to the lungs and a brain CT showed a frontal hemorrhage of probably metastatic origin. The latter eventually progressed to cause the death of the patient. Pathology of the brain hematoma disclosed a choriocarcinoma within the brain AVM nidus. CONCLUSIONS: The case presented is an extremely rare confluence of choriocarcinoma brain metastasis within an AVM. The hemorrhagic onset could have been secondary to bleeding from either of the two histological components of the subjacent mixed pathological lesion.

Migraine treatment consensus document of the Spanish Society of Neurology (SEN), Spanish Society of Family and Community Medicine (SEMFYC), Society of Primary Care Medicine (SEMERGEN) and Spanish Association of Migraine and Headache (AEMICE) on migraine treatment. / Documento de consenso de la Sociedad Española de Neurología (SEN), Sociedad Española de Medicina de Familia y Comunitaria (SEMFYC), Sociedad de Medicina de Atención Primaria (SEMERGEN) y Asociación Española de Migraña y Cefalea (AEMICE) sobre el tratamiento de la migraña.

Migraine is a disease with a high prevalence and incidence, in addition to being highly disabling, causing a great impact on the patient's quality of life at a personal, family and work level, but also social, given its high expense due to its direct (care) and indirect (presenteeism and work absenteeism) costs. The multiple and recent developments in its pathophysiological knowledge and in its therapy require updating and, therefore, in this article the Spanish scientific societies most involved in its study and treatment (SEN, SEMFYC and SEMERGEN), together with the Association Spanish Association for Patients with Migraine and other Headaches (AEMICE), we have developed these updated care recommendations. We reviewed the treatment of migraine attacks, which consisted mainly of the use of NSAIDs and triptans, to which ditans and gepants have been added. We also discuss preventive treatment consisting of oral preventive drugs, botulinum toxin, and treatments that block the action of calcitonin-related peptide (CGRP). Finally, we emphasize that pharmacological treatments must be complementary to carrying out general measures consisting of identifying and managing/deletion the precipitating factors of the attacks and the chronicizing factors, controlling the comorbidities of migraine and eliminating analgesic overuse.

Long-term safety of OnabotulinumtoxinA treatment in chronic migraine patients: a five-year retrospective study.

Background: Real-world studies have shown the sustained therapeutic effect and favourable safety profile of OnabotulinumtoxinA (BoNTA) in the long term and up to 4 years of treatment in chronic migraine (CM). This study aims to assess the safety profile and efficacy of BoNTA in CM after 5 years of treatment in a real-life setting. Methods: We performed a retrospective chart review of patients with CM in relation to BoNTA treatment for more than 5 years in 19 Spanish headache clinics. We excluded patients who discontinued treatment due to lack of efficacy or poor tolerability. Results: 489 patients were included [mean age 49, 82.8% women]. The mean age of onset of migraine was 21.8 years; patients had CM with a mean of 6.4 years (20.8% fulfilled the aura criteria). At baseline, patients reported a mean of 24.7 monthly headache days (MHDs) and 15.7 monthly migraine days (MMDs). In relation to effectiveness, the responder rate was 59.1% and the mean reduction in MMDs was 9.4 days (15.7 to 6.3 days; p < 0.001). The MHDs were also reduced by 14.9 days (24.7 to 9.8 days; p < 0.001). Regarding the side effects, 17.5% experienced neck pain, 17.3% headache, 8.5% eyelid ptosis, 7.5% temporal muscle atrophy and 3.2% trapezius muscle atrophy. Furthermore, after longer-term exposure exceeding 5 years, there were no serious adverse events (AE) or treatment discontinuation because of safety or tolerability issues. Conclusion: Treatment with BoNTA led to sustained reductions in migraine frequency, even after long-term exposure exceeding 5 years, with no evidence of new safety concerns.

Post-COVID-19 fatigue: the contribution of cognitive and neuropsychiatric symptoms.

Fatigue in its many forms of physical, mental, and psychosocial exhaustion is a common symptom of post-COVID-19 condition, also known as "Long COVID." Persistent fatigue in COVID-19 patients is frequently accompanied by cognitive dysfunction and neuropsychiatric symptoms; however, less is known about the relationships between these components of post-COVID-19 condition and fatigue itself. Consequently, the present study sought to (1) distinguish the types of fatigue experienced by participants, and (2) investigate whether cognitive deficits across various domains and neuropsychiatric conditions predicted these different types of fatigue. The study included 136 COVID-19 patients referred for neuropsychological evaluation due to cognitive complaints 8 months on average after SARS-CoV-2 infection. Measures included self-reported fatigue (physical, cognitive, and psychosocial), neuropsychiatric questionnaires (assessing symptoms of depression, anxiety, apathy, and executive functioning), a comprehensive neuropsychological assessment, and self-reported quality of life and everyday functioning. Results showed that reports of clinical significant fatigue were pervasive in our sample (82.3% of participants), with physical fatigue rated highest on average relative to the subscale maximum. Elevated levels of apathy, anxiety, and executive dysfunction in neuropsychiatric measures along with executive and attentional difficulties on cognitive tests were found to be consistently important predictors among different types of fatigue. This implicates both cognitive and neuropsychiatric symptoms as predictors of fatigue in post-COVID-19 condition, and stresses the importance of a holistic approach in assessing and considering potential treatment for COVID-19 patients experiencing fatigue.

Neuropsychological deficits in patients with cognitive complaints after COVID-19.

BACKGROUND: While much of the scientific focus thus far has been on cognitive sequelae in patients with severe COVID-19, subjective cognitive complaints are being reported across the spectrum of disease severity, with recent studies beginning to corroborate patients' perceived deficits. In response to this, the aims of this study were to (1) explore the frequency of impaired performance across cognitive domains in post-COVID patients with subjective complaints and (2) uncover whether impairment existed within a single domain or across multiple. METHODS: Sixty-three patients with subjective cognitive complaints post-COVID were assessed with a comprehensive protocol consisting of various neuropsychological tests and mood measures. Cognitive test performance was transformed into T scores and classified based on recommended guidelines. After performing a principal component analysis to define cognitive domain factors, distributions of test scores within and across domains were analyzed. RESULTS: Results revealed pervasive impact on attention abilities, both as the singularly affected domain (19% of single-domain impairment) as well as coupled with decreased performance in executive functions, learning, and long-term memory. These salient attentional and associated executive deficits were largely unrelated to clinical factors such as hospitalization, disease duration, biomarkers, or affective measures. DISCUSSION: These findings stress the importance of comprehensive evaluation and intervention to address cognitive sequelae in post-COVID patients of varying disease courses, not just those who were hospitalized or experienced severe symptoms. Future studies should investigate to what extent these cognitive abilities are recuperated over time as well as employ neuroimaging techniques to uncover underlying mechanisms of neural damage.

Postdural puncture headache: impact of needle type, a randomized trial.

BACKGROUND CONTEXT: The most common adverse event after a lumbar puncture (LP) is a headache: In anaesthesiology, well studied is the protective effect of atraumatic spinal needles, and they are routinely used. However, this is less well known in diagnostic LP, and neurologists use atraumatic needles in less than 2% of times. PURPOSE: The purpose of this study was to define the impact of needle type, atraumatic (Sprotte [S]) versus traumatic (Quincke [Q]) on postdural puncture headache (PDPH) incidence. STUDY DESIGN: The study is based on a prospective, randomized, and simple-blinded clinical trial. PATIENT SAMPLE: Patients older than 14 years were scheduled for a diagnostic or therapeutic LP. OUTCOME MEASURES: The outcome measure included the development of PDPH according to the International Headache Association criteria. METHODS: Patients fulfilling eligibility criteria were randomly allocated to one of two kinds of spinal needle: atraumatic or S-type or traumatic or Q-type. They were interviewed on days 2 and 7 about the development of PDPH. RESULTS: The incidence of PDPH was 22.43% with Q-type needle and 8.51% with S-type needle, p=.04. The duration of PDPH in patients in the S-type was 1 day or less, compared with a median of 4.14 days in the Q-type (p=.00). In the logistic regression model, the S-type needle together with the age of the patient were the only two statistically significant factors in the development of postlumbar puncture headache (PLPH), both of them being protective. CONCLUSIONS: We found a lower incidence of PDPH with atraumatic needles, and it was statistically significant compared with the traumatic needles. Our study confirms the effectiveness of the atraumatic needles to prevent PDPH.

[Posterior reversible encephalopathy in a case of late-onset eclampsia]. / Encefalopatia posterior reversible en un caso de eclampsia tardia.

INTRODUCTION: Posterior reversible encephalopathy syndrome (PRES) is a clinical-radiological syndrome with acute or sub-acute presenting symptoms characterised by the presence of headache, vomiting, epileptic seizures, visual disorders and altered level of consciousness associated to lesions mainly located in the white matter of the posterior regions of the brain. CASE REPORT: A 32-year-old female who developed PRES in the postpartum period secondary to late-onset eclampsia. Ten days after giving birth, the patient presented a clinical picture consisting in headache, epileptic seizures, blindness and deterioration of the level of consciousness. The magnetic resonance imaging scan confirmed the predominant involvement of posterior white matter. CONCLUSIONS: Although eclampsia is a typical condition in pregnancy and the immediate postpartum period, it must be remembered that there is also a late-onset form that may occur after the birth and might be the cause of other syndromes such as PRES. Although the prognosis in these cases is usually favourable, treatment must be established as early as possible, with rapid control of the blood pressure and seizures in order to avoid permanent brain damage. This syndrome must always be taken into account in women with epileptic seizures or other neurological symptoms during the postpartum period.

TITLE: Encefalopatia posterior reversible en un caso de eclampsia tardia.Introduccion. El sindrome de encefalopatia posterior reversible (SEPR) es un sindrome clinico-radiologico de presentacion aguda o subaguda que se caracteriza por la presencia de cefalea, vomitos, crisis epilepticas, trastornos visuales y alteracion del nivel de conciencia asociado a lesiones localizadas fundamentalmente en la sustancia blanca de regiones posteriores cerebrales. Caso clinico. Mujer de 32 años que desarrollo un SEPR en el periodo posparto secundario a eclampsia tardia. La paciente presento 10 dias despues del parto un cuadro clinico consistente en cefalea, crisis epilepticas, ceguera y deterioro del nivel de conciencia. El estudio de imagen con resonancia magnetica confirmo la afectacion de la sustancia blanca de predominio posterior. Conclusiones. Aunque la eclampsia es una entidad tipica del embarazo y puerperio inmediato, es necesario recordar que tambien puede producirse de forma tardia tras el parto y que puede ser la causa de otros sindromes, como el SEPR. Aunque en estos casos el pronostico suele ser favorable, el tratamiento debe ser precoz, efectuando un rapido control de la tension arterial y las convulsiones con el fin de evitar un daño cerebral permanente. Es necesario considerar siempre este sindrome en mujeres con crisis epilepticas u otros sintomas neurologicos durante el posparto.

Histology of a cerebral hemorrhage: AVM as a seat of a metastatic choriocarcinoma / Histología de un hematoma cerebral: MAV como asiento de una metástasis de coriocarcinoma

Introduction: There are published cases of cerebral haemorrhage secondary to vascular alterations caused by choriocarcinoma metastases. However, it is extremely rare to find this type of bleeding secondary to an association of such a metastasis with a brain arteriovenous malformation (AVM). Clinical case: We present the case of a 19-year-old male who came to the Emergency Department complaining of intense headache of abrupt onset. His physical examination revealed a striking increase in size of the right testicle of tumoral origin. Chest X-ray evidenced metastasis to the lungs and a brain CT showed a frontal haemorrhage of probably metastatic origin. The latter eventually progressed to cause the death of the patient. Pathology of the brain hematoma disclosed a choriocarcinoma within the brain AVM nidus. Conclusions: The case presented is an extremely rare confluence of choriocarcinoma brain metastasis within an AVM. The haemorrhagic onset could have been secondary to bleeding from either of the two histological components of the subjacent mixed pathological lesion

Introducción: Aunque se han descrito casos de hemorragia cerebral secundaria a anomalías vasculares inducidas por metástasis de coriocarcinomas, es excepcional el que una hemorragia cerebral se deba a una asociación de malformación arteriovenosa con metástasis de coriocarcinoma. Caso clínico: Presentamos el casos de un paciente varón de 19 años que acudió a urgencias por cefalea brusca, intensa. Su exploración física demostró un tumor testicular de gran tamaño. El estudio radiológico mostró metástasis pulmonares, y la TC cerebral evidenció un hematoma frontal sospechoso de tener origen metastásico. La evolución de este hematoma fue eventualmente la causa de la muerte del paciente. La anatomía patológica del hematoma demostró una metástasis de coriocarcinoma en el seno del nidus de una MAV. Conclusiones: Se trata de un caso extremadamente infrecuente de colisión de una metástasis de coriocaricnoma en el seno de una MAV cerebral. El debut hemorrágico pudo deberse a sangrado de cualquiera de los dos componentes patológicos de esta lesión mixta

Encefalopatía posterior reversible en un caso de eclampsia tardía / Posterior reversible encephalopathy in a case of late-onset eclampsia

Introducción. El síndrome de encefalopatía posterior reversible (SEPR) es un síndrome clínico-radiológico de presentación aguda o subaguda que se caracteriza por la presencia de cefalea, vómitos, crisis epilépticas, trastornos visuales y alteración del nivel de conciencia asociado a lesiones localizadas fundamentalmente en la sustancia blanca de regiones posteriores cerebrales. Caso clínico. Mujer de 32 años que desarrolló un SEPR en el período posparto secundario a eclampsia tardía. La paciente presentó 10 días después del parto un cuadro clínico consistente en cefalea, crisis epilépticas, ceguera y deterioro del nivel de conciencia. El estudio de imagen con resonancia magnética confirmó la afectación de la sustancia blanca de predominio posterior. Conclusiones. Aunque la eclampsia es una entidad típica del embarazo y puerperio inmediato, es necesario recordar que también puede producirse de forma tardía tras el parto y que puede ser la causa de otros síndromes, como el SEPR. Aunque en estos casos el pronóstico suele ser favorable, el tratamiento debe ser precoz, efectuando un rápido control de la tensión arterial y las convulsiones con el fin de evitar un daño cerebral permanente. Es necesario considerar siempre este síndrome en mujeres con crisis epilépticas u otros síntomas neurológicos durante el posparto (AU)

Introduction. Posterior reversible encephalopathy syndrome (PRES) is a clinical-radiological syndrome with acute or subacute presenting symptoms characterised by the presence of headache, vomiting, epileptic seizures, visual disorders and altered level of consciousness associated to lesions mainly located in the white matter of the posterior regions of the brain. Case report. A 32-year-old female who developed PRES in the postpartum period secondary to late-onset eclampsia. Ten days after giving birth, the patient presented a clinical picture consisting in headache, epileptic seizures, blindness and deterioration of the level of consciousness. The magnetic resonance imaging scan confirmed the predominant involvement of posterior white matter. Conclusions. Although eclampsia is a typical condition in pregnancy and the immediate postpartum period, it must be remembered that there is also a late-onset form that may occur after the birth and might be the cause of other syndromes such as PRES. Although the prognosis in these cases is usually favourable, treatment must be established as early as possible, with rapid control of the blood pressure and seizures in order to avoid permanent brain damage. This syndrome must always be taken into account in women with epileptic seizures or other neurological symptoms during the postpartum period (AU)