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Producción Científica, Background Headache is one of the most frequently reported symptoms in post-COVID patients. The clinical phenotype of COVID-19 headache combines phenotypic features of both tension-type headache (TTH) and migraine. We aimed to assess the efectiveness, side efects and predictors of amitriptyline (AMT) response in a real-world study setting. Methods We performed an observational multicentric study with a retrospective cohort. All consecutive patients with con frmed COVID-19 infection who received AMT for post-COVID headache from March 2020 to May 2021 were included. Response was evaluated by the reduction in the number of headache days per month (HDM) between weeks 8 and 12, compared with the baseline. We explored which variables were associated with a higher probability of response to AMT. Results Forty-eight patients were eligible for the study, 40/48 (83.3%) females, aged 46.85 (SD: 13.59) years. Patients had history of migraine 15/48 (31.3%) or TTH 5/48 (10.4%). The mean reduction of HDM was 9.6 (SD: 10.9; 95% CI 6.5, 12.7) days. Only 2/48 (5%) of patients discontinued AMT due to poor tolerability. History of TTH (10.9, 95% CI 1.3, 20.6) and nausea (−8.5, 95% CI −14.6, −2.5) were associated with AMT response. Conclusions This study provides real-world evidence of the potential beneft of AMT in patients with post-COVID-19 headache, especially in patients with history of TTH and without concomitant nausea., Ministerio de Economía y Competitividad (Instituto de Salud Carlos III) & Unión Europea (Fondo Social Europeo, FSE+) a través del Río Hortega Beca (CM21/00178), Publicación en abierto financiada por el Consorcio de Bibliotecas Universitarias de Castilla y León (BUCLE), con cargo al Programa Operativo 2014ES16RFOP009 FEDER 2014-2020 DE CASTILLA Y LEÓN, Actuación:20007-CL - Apoyo Consorcio BUCLE

In the few last years, a new family of drugs, anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs), has been developed for migraine therapy. Anti-CGRP mAbs are highly effective, but the current limited experience with their use and their high-cost warrant establishing certain rules of use.The present review provides an overview of the management of migraine patients, especially those who are undergoing treatment with anti-CGRP mAbs.Thanks to new research focused on the pathophysiology of migraine, and the discovery that CGRP plays a key role in its etiopathogenesis, new drugs targeting CGRP have been developed. These drugs have led to a paradigm shift, anticipating new and stimulating possibilities in migraine treatment. While physicians and patients are full of expectation about the advantages of this new family of drugs, there are still obstacles to overcome in order to make the best use of them. It is essential to form multidisciplinary teams that can identify patients who will benefit from these therapies, conducting cost-effective treatments. The follow-up of these therapies in the coming years is paramount due to the lack of experience in the management of these drugs and the peculiarity of disease evolution in migraine patients.

Background Headache is a frequent symptoms of coronavirus disease 2019 (COVID-19). Its long-term evolution remains unknown. We aim to evaluate the long-term duration of headache in patients that presented headache during the acute phase of COVID-19. Methods This is a post-hoc multicenter ambisective study including patients from six different third-level hospitals between 1 March and 27 April 2020. Patients completed 9 months of neurological follow-up. Results We included 905 patients. Their median age was 51 (IQR 45–65), 66.5% were female, and 52.7% had a prior history of primary headache. The median duration of headache was 14 (6–39) days; however, the headache persisted after 3 months in 19.0% (95% CI: 16.5–21.8%) and after 9 months in 16.0% (95% confidence interval: 13.7–18.7%). Headache intensity during the acute phase was associated with a more prolonged duration of headache (Hazard ratio 0.655; 95% confidence interval: 0.582–0.737). Conclusion The median duration of headache was 2 weeks, but in approximately a fifth of patients it became persistent and followed a chronic daily pattern.

Objective The objective is to summarize the knowledge on the epidemiology, pathophysiology and management of secondary headache attributed to SARS-CoV-2 infection and vaccination; as well as to delineate their impact on primary headache disorders. Methods This is a narrative review of the literature regarding primary and secondary headache disorders in the setting of COVID-19 pandemic. We conducted a literature search in 2022 on PubMed, with the keywords “COVID 19” or “vaccine” and “headache” to assess the appropriateness of all published articles for their inclusion in the review. Results Headache is a common and sometimes difficult-to-treat symptom of both the acute and post-acute phase of SARS-CoV-2 infection. Different pathophysiological mechanisms may be involved, with the trigeminovascular system as a plausible target. Specific evidence-based effective therapeutic options are lacking at present. Headache attributed to SARS-CoV-2 vaccinations is also common, its pathophysiology being unclear. People with primary headache disorders experience headache in the acute phase of COVID-19 and after vaccination more commonly than the general population. Pandemic measures, forcing lifestyle changes, seemed to have had a positive impact on migraine, and changes in headache care (telemedicine) have been effectively introduced. Conclusions The ongoing COVID-19 pandemic is a global challenge, having an impact on the development of secondary headaches, both in people with or without primary headaches. This has created opportunities to better understand and treat headache and to potentiate strategies to manage patients and ensure care.

This is a multicenter prospective observational study which included a large cohort (n = 397) of allogeneic (allo-HSCT) (n = 311) and autologous (ASCT) hematopoietic stem cell transplant (n = 86) recipients who were monitored for antibody detection within 3 to 6 weeks after complete SARS-CoV-2 vaccination from February 1st 2021 to July 20th 2021. Most patients (n = 387, 97.4%) received mRNA-based vaccines. Most of recipients (93%) were vaccinated more than 1 year after transplant. Detectable SARS-CoV-2-reactive antibodies were observed in 242 (78%) of allo-HSCT and in 73 (85%) of ASCT recipients. Multivariate analysis in allo-HSCT recipients identified lymphopenia

The long-term clinical efficacy of SARS-CoV-2 vaccines according to antibody response in immunosuppressed patients such as hematological patients has been little explored. A prospective multicenter registry-based cohort study conducted from December 2020 to July 2022 by the Spanish Transplant and Cell Therapy group, was used to analyze the relationship of antibody response over time after full vaccination (at 3-6 weeks, 3, 6 and 12 months) (2 doses) and of booster doses with breakthrough SARS-CoV-2 infection in 1551 patients with hematological disorders. At a median follow-up of 388 days after complete immunization, 266 out of 1551 (17%) developed breakthrough SARS-CoV-2 infection at median of 86 days (range 7-391) after full vaccination. The cumulative incidence was 18% [95% confidence interval (C.I.), 16-20%]. Multivariate analysis identified higher incidence in chronic lymphocytic leukemia patients (29%) and with the use of corticosteroids (24.5%), whereas female sex (15.5%) and more than 1 year after last therapy (14%) were associated with a lower incidence (p 0.05 for all comparisons). Median antibody titers at different time points were significantly lower in breakthrough cases than in non-cases. A serological titer cut-off of 250 BAU/mL was predictive of breakthrough infection and its severity. SARS-CoV-2 infection-related mortality was encouragingly low (1.9%) in our series. Our study describes the incidence of and risk factors for COVID-19 breakthrough infections during the initial vaccination and booster doses in the 2021 to mid-2022 period. The level of antibody titers at any time after 2-dose vaccination is strongly linked with protection against both breakthrough infection and severe disease, even with the Omicron SARS-CoV-2 variant.

Epigenetic changes such as DNA methylation were observed in drug-resistant temporal lobe epilepsy (DR-TLE), a disease that affects 25-30% of epilepsy patients. The main objective is to simultaneously describe DNA methylation patterns associated with DR-TLE in hippocampus, amygdala, surrounding cortex to the epileptogenic zone (SCEZ), and peripheral blood. An Illumina Infinium MethylationEPIC BeadChip array was performed in 19 DR-TLE patients and 10 postmortem non-epileptic controls. Overall, 32, 59, and 3210 differentially methylated probes (DMPs) were associated with DR-TLE in the hippocampus, amygdala, and SCEZ, respectively. These DMP-affected genes were involved in neurotrophic and calcium signaling in the hippocampus and voltage-gated channels in SCEZ, among others. One of the hippocampus DMPs (cg26834418 (CHORDC1)) showed a strong blood-brain correlation with BECon and IMAGE-CpG, suggesting that it could be a potential surrogate peripheral biomarker of DR-TLE. Moreover, in three of the top SCEZ's DMPs (SHANK3, SBF1, and MCF2L), methylation status was verified with methylation-specific qPCR. The differentially methylated CpGs were classified in DMRs: 2 in the hippocampus, 12 in the amygdala, and 531 in the SCEZ. We identified genes that had not been associated to DR-TLE so far such as TBX5, EXOC7, and WRHN. The area with more DMPs associated with DR-TLE was the SCEZ, some of them related to voltage-gated channels. The DMPs found in the amygdala were involved in inflammatory processes. We also found a potential surrogate peripheral biomarker of DR-TLE. Thus, these results provide new insights into epigenetic modifications involved in DR-TLE.

Several variables have been reported to be associated with anti-calcitonin gene-related peptide (CGRP) receptor or ligand antibody response, but with differing results. Our objective was to determine whether machine-learning (ML)-based models can predict 6-, 9- and 12-month responses to anti-CGRP receptor or ligand therapies among migraine patients.We performed a multicenter analysis of prospectively collected data from patients with migraine receiving anti-CGRP therapies. Demographic and clinical variables were collected. Response rates in the 30% to 50% range, or at least 30%, in the 50% to 75% range, or at least 50%, and response rate of at least 75% regarding the reduction in the number of headache days per month at 6, 9 and 12 months were calculated. A sequential forward feature selector was used for variable selection and ML-based predictive models for the response to anti-CGRP therapies at 6, 9 and 12 months, with model accuracy not less than 70%, were generated.A total of 712 patients were included, 93% were women, and the mean (SD) age was 48 (11.6) years. Eighty-four percent of patients had chronic migraine. ML-based models using headache days/month, migraine days/month and the Headache Impact Test (HIT-6) yielded predictions with an F1 score range of 0.70-0.97 and an area under the receiver-operating curve score range of 0.87-0.98. SHAP (SHapley Additive exPlanations) summary plots and dependence plots were generated to evaluate the relevance of the factors associated with the prediction of the above-mentioned response rates.Our results show that ML models can predict anti-CGRP response at 6, 9 and 12 months. This study provides a predictive tool that can be used in a real-world setting.

Epilepsy is a disabling neurological disease that affects 2% of the population. Drug-resistant epilepsy (DRE) affects 25-30% of epilepsy patients. Understanding its underlying mechanisms is key to adequately manage this condition. To analyze the main epigenetic marks of DRE an epigenome-wide association study was carried out including samples from different regions of DRE patients’ brain and peripheral blood. An Illumina Infinium MethylationEPIC BeadChip array including cortex, hippocampus, amygdala, and peripheral blood from DRE subjected to neurosurgical resection of the epileptogenic zone was used. Overall, 32, 59, 3210, and 6 differentially methylated probes (DMPs) associated with DRE were found in the hippocampus, amygdala, cortex, and peripheral blood, respectively. These DMPs harbored 19, 28, 1574, and 7 genes, respectively, which play different roles in processes such as neurotrophic or calcium signaling. Three of the top DMPs observed in cortex were validated with methylation specific qPCR. Moreover, 163 DMPs associated with neurosurgery response at 6 months were found in the hippocampus. Genes located on these DMPs were involved in diverse processes such as synaptic signaling and central nervous system development. Besides 3 DMPs in blood samples were associated with response to neurosurgery at 12 months. In conclusion, the present study reports genome-wide DNA methylation changes across different regions of the DRE brain. These changes could be useful for further studies to disentangle the bases of DRE to search for therapeutic alternatives for this disease. Furthermore, they could also help identify patients likely to respond to neurosurgery.

Cytomegalovirus (CMV) DNAemia and CMV disease have been reported as more frequent in patients undergoing haploidentical allogeneic hematopoietic stem cell transplantation (Haplo-HSCT) than in those receiving HLA-matched allografts. This could be due to impaired CMV-specific T-cell reconstitution. Here, we conducted a multicenter observational study to assess CMV pp65 and IE-1-specific T cells kinetics in patients undergoing unmanipulated Haplo-HSCT with posttransplant cyclophosphamide (PT/Cy-haplo) and compared it with patients allografted with HLA-matched donors. Plasma CMV DNA load was monitored by real-time PCR and enumeration of CMV-specific IFN-γ-producing CD8+ and CD4+ T cells was performed by flow cytometry for intracellular cytokine staining at days +30, +60, +90, and +180 after transplantation. CMV DNAemia developed in 62 patients, occurring with comparable frequency in PT/Cy-haplo and MRD/MUD recipients (P = 0.14). There were no significant differences across groups in the number of patients either displaying detectable CMV-specific CD8+ and CD4+ T-cell responses or acquiring CMV-specific T-cell levels conferring protection against subsequent infection. CMV-specific T-cell counts were comparable between groups at most time points examined, irrespective of whether CMV DNAemia occurred or not prior to monitoring. Collectively the data suggest that PT/Cy-haplo recipients may reconstitute CMV-specific T-cell immunity to the same extent as patients undergoing HLA-matched allo-HSCT.

The emergence of triptans represented a breakthrough in the treatment of migraine, but in clinical practice, patients describe symptoms that resemble those of a hangover after taking them. We propose the use of the Hangover Symptoms Scale (HSS) to evaluate this syndrome in patients that take triptans, which may help identify patients at higher risk of presenting these adverse effects that may interfere with therapeutic compliance.A cross-sectional observational pilot study with prospective data collection through a clinical-demographic questionnaire and the HSS was carried out on patients with migraine treated in headache units in 3 tertiary hospitals in Madrid.Sixty-six patients were included in the study. The median HSS was 4 and all symptoms were present in at least 15% of the patients, with difficulty to concentrate being the most frequent (57.6%). No significant differences were found between the presence of a higher HSS score and the sociodemographic characteristics of the patient or his migraine. The presence of aura was associated with a higher percentage of trembling (P = 0.029) and fatigue (nonvisual, polymodal auras; P = 0.017).According to our study, triptans are responsible for a set of symptoms overlapping with those that occur during a hangover. Therefore, we propose that the HSS could be a useful tool for the evaluation and quantification of these effects in patients receiving triptans. In addition, we found that clinical features could be more frequently associated with the appearance of these adverse effects that, however, are not related to any particular patient profile.

Precise identification of patients at highest risk for developing Cytomegalovirus (CMV) DNAemia may improve CMV infection management in the allogeneic hematopoietic stem cell transplantation (allo-HSCT) setting. Here, we studied the potential use of detecting free CMV micro(mi)RNAs circulating in plasma for predicting CMV DNAemia in this clinical scenario. A total of 62 adult allo-HSCT recipients were included in this prospective observational multicenter study. Plasma CMV DNA load was monitored using the CMV RealTime CMV PCR (Abbott Molecular, Des Plaines, IL, USA). Detection of mature CMV miRNAs in plasma drawn by days + 7, + 14 and + 30 after allo-HSCT was performed using the miScript PCR System (Qiagen, Hilden, Germany). Assays could be optimized for five out of the seven targeted CMV miRNAs: UL36-5p, US33-5p, UL148D, UL22A-5p and UL112-3p. Of the 62 patients included in the study, 42 developed a first episode of CMV DNAemia at a median of 35 days after allo-HSCT. All targeted CMV miRNA were detected early after transplantation, with CMV miRNA US33-5p and UL112-3p the most commonly found species at any time point; nevertheless, neither the detection rate of CMV miRNAs nor their abundance allowed discrimination between patients with subsequent CMV DNAemia and those with no CMV DNAemia. The data presented herein do not support any predictive utility of these CMV miRNAs for first episodes of CMV DNAemia in a cohort consisting primarily of allo-HSCT patients receiving haploidentical allografts.

Deciding on the continuous treatment of chronic diseases is vital in terms of economy, quality of life, and time. We present a holistic data mining approach that addresses the prediction of the therapeutic response in a panoramic and feedback way while unveiling relevant medical factors. Panoramic prediction makes it possible to decide whether the treatment will be beneficial without using previous knowledge and without involving unnecessary treatments. Feedback prediction can be more accurate prediction since it considers the results of previous stages of the treatment. A novel label encoding called simulated annealing and rounding (SAR) encoding is also proposed to help improve the accuracy of prediction in both approaches. To unveil the medical factors that make the treatment effective for patients, various techniques are applied to the prediction models found through the proposed approaches. Finally, this methodology is applied in the realistic scenario of analyzing electronic medical records of migraineurs under BoNT-A treatment. The results show a significant improvement in accuracy due to the use of SAR encoding, from close to 60% (baseline) to 75% with panoramic prediction, and up to around 90% when using feedback prediction. Furthermore, the following factors have been found to be relevant when predicting the migraine treatment responses: migraine time evolution, unilateral pain, analgesic abuse, headache days, and the retroocular component. According to doctors, these factors are also medically relevant and in alignment with the medical literature.

Cytomegalovirus (CMV) DNAemia and CMV disease have been reported as more frequent in patients undergoing haploidentical allogeneic hematopoietic stem cell transplantation (Haplo-HSCT) than in those receiving HLA-matched allografts. This could be due to impaired CMV-specific T-cell reconstitution. Here, we conducted a multicenter observational study to assess CMV pp65 and IE-1-specific T cells kinetics in patients undergoing unmanipulated Haplo-HSCT with posttransplant cyclophosphamide (PT/Cy-haplo) and compared it with patients allografted with HLA-matched donors. Plasma CMV DNA load was monitored by real-time PCR and enumeration of CMV-specific IFN-γ-producing CD8

Stigma manifests both in prejudices and rejection from society towards patients who suffer from a specific pathology, and by patient’s internalization of this discrimination, with the consequent repercussions on their state of mind and quality of life. The aim of the study was to quantify the stigma associated with migraine and analyze whether it is related to the clinical-demographic characteristics of the patients, as well as the possible impact on their daily lives. The stigma scale for chronic illness (SSCI) and other questionnaires were administered to 56 patients with episodic migraine (EM), 18 with chronic migraine (CM), and 21 with epilepsy, as a control group. The mean SSCI score was higher (51.6 ± 15.0) in the CM group than in the EM (45.0 ± 13.5) and epilepsy (47.6 ± 15.5) groups, without reaching statistical significance. In addition, the score was higher in patients who were unemployed, divorced, and in those who had migraine with aura. A statistically significant correlation was found between the SSCI score and the impact of migraine on daily life, the presence of stress, anxiety and depression, and low self-esteem. There is a stigma around migraine in our society, which seems to be more prevalent in patients with certain socio-demographic characteristics, and that is related to stress, mood alterations, and low self-esteem. Trying to reduce stigma could contribute to improve the control of migraine and reduce the impact of the disease at a socio-economic level.

BACKGROUND Sundown syndrome (SS) is the onset or worsening of behavioral symptoms in the evening in patients with dementia. OBJECTIVE To identify the differential clinical profile of patients with dementia who present SS. METHODS A cross-sectional, case-control observational study was conducted by retrospectively reviewing the medical records of patients with dementia in a specialized Memory Unit. We compared the characteristics of patients with and without SS, including sociodemographic variables, etiology, and severity of the dementia, behavioral symptoms, sleep disorders (considering insomnia and hypersomnia), other diseases and treatments employed. We identified the factors related to SS and conducted a logistic regression analysis to establish a predictive nomogram. RESULTS Of the 216 study patients with dementia, 41 (19%) had SS. There was a predominance of women (2.4:1), advanced age (p = 0.0001), dependence (p

Background. Donor specific antibodies (DSAs) are preformed IgG antibodies with specificity against HLA molecules not shared with the donor that can lead to graft failure (GF) in the setting of mismatched HSCT. The aim of this study is to report the experience of the Spanish Group of Hematopoietic Transplant (GETH-TC) in patients with DSAs undergoing haplo-HSCT. Methods. Patients undergoing haplo-HSCT in centers from the GETH-TC from 2013 to 2021 were included in the study. DSAs were analyzed with a solid-phase single-antigen immunoassay (Luminex®); monitoring was performed prior to desensitization, prior to infusion and after infusion. Desensitization strategies used depended on center experience, immunofluorescence intensity, complement fixation and type of antibodies. Results. 59 haplo-HSCT with DSAs were performed in 57 patients in 13 centers. Characteristics of the population are shown in Table 1. 53 (93%) patients were female (91% with prior pregnancies). All patients lacked a suitable alternative donor. 51 (89%) received peripheral blood as stem cell source. Conditioning was myeloablative in 58% and all patients received post-transplant cyclophosphamide based GVHD prophylaxis; 3 (5%) patients received also ATG. 28 (49%) patients presented anti-HLA class I DSAs 22 of them with >5000MFI), 14 (25%) presented anti-HLA class II (6 with >5000MFI) and 15 (26%) presented both anti-HLA class I and II DSAs (13 with >5000MFI). Five patients did not receive desensitization treatment, 4 of them with After a median follow-up of 24 months, 2-year OS and EFS were 52% and 42%, respectively. 2-year cumulative incidence of relapse at was 14% and NRM was 41%. Cumulative incidence of grade II-IV aGVHD at day 180 was 13% and chronic GVHD was 25%. Conclusions. The use of desensitization treatment guided by DSAs intensity kinetics constitute an effective approach with high rates of engraftment for patients with DSAs in need for an haplo-HSCT lacking an alternative suitable donor, including non-malignant disorders. Figure 1 Figure 1. Disclosures Bailen: Pfizer, Kite-Gilead, Gilead: Honoraria. Oarbeascoa: Gilead: Honoraria, Speakers Bureau. Kwon: Novartis, Celgene, Gilead, Pfizer: Consultancy, Honoraria.

Background: Dementia is a neurodegenerative disease whose prevalence is rising, and the need for assistance to patients becomes indispensable. The different types of dementia and their treatments have been widely studied; however, the health status of caregivers also requires our attention. Objective: The aim of our research was to evaluate whether caregivers of patients with dementia consume more medications than the general population, indicating underlying pathologies. Methods: A total of 91 caregivers of dementia patients were interviewed and their answers were compared with those from a control group of 48 people, taking into account demographic data, characteristics of patients and caregivers, pharmacological and nonpharmacological treatments and burden. Results: Caregivers showed a significantly higher consumption of anxiolytics, antidepressants and antiplatelets (22.3, 13.2 and 11%, respectively) than the control group (14.6, 0 and 0%, respectively). Moreover, 45.1% of the caregivers used nonpharmacological therapies compared with 6.2% of the control group. There was a tendency to take more medications in those caregivers suffering from burden and those who had to take care of patients with behavioral changes. Conclusion: Caregivers of dementia patients need more pharmacological and nonpharmacological therapies. They are a risk group that needs better care from the health system.