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Background and purpose: According to the latest European guidelines, discontinuation of monoclonal antibodies against calcitonin gene‐related peptide (anti‐CGRP MAb) may be considered after 12–18 months of treatment. However, some patients may worsen after discontinuation. In this study, we assessed the response following treatment resumption. Methods: This was a prospective study conducted in 14 Headache Units in Spain. We included patients with response to anti‐CGRP MAb with clinical worsening after withdrawal and resumption of treatment. Numbers of monthly migraine days (MMD) and monthly headache days (MHD) were obtained at four time points: before starting anti‐CGRP MAb (T‐baseline); last month of first treatment period (T‐suspension); month of restart due to worsening (T‐worsening); and 3 months after resumption (T‐reintroduction). The response rate to resumption was calculated. Possible differences among periods were analysed according to MMD and MHD. Results: A total of 360 patients, 82% women, with a median (interquartile range [IQR]) age at migraine onset of 18 (12) years. The median (IQR) MHD at T‐baseline was 20 (13) and MMD was 5 (6); at T‐suspension, the median (IQR) MHD was 5 (6) and MMD was 4 (5); at T‐worsening, the median (IQR) MHD was 16 (13) and MMD was 12 (6); and at T‐reintroduction, the median (IQR) MHD was 8 (8) and MHD was 5 (5). In the second period of treatment, a 50% response rate was achieved by 57.4% of patients in MHD and 65.8% in MMD. Multivariate models showed significant differences in MHD between the third month after reintroduction and last month before suspension of first treatment period (p < 0.001). Conclusion: The results suggest that anti‐CGRP MAb therapy is effective after reintroduction. However, 3 months after resumption, one third of the sample reached the same improvement as after the first treatment period. [ABSTRACT FROM AUTHOR]

Objective To evaluate clinical characteristics, effectiveness, and tolerability of preventive anti- calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) in the elderly. Anti-CGRP mAbs have demonstrated efficacy and safety in patients with migraine although there is limited information regarding the elderly. Design We performed a multicenter case-control study of cases (patients over 65 years old) and controls (sex-matched patients under 55 years old) with migraine receiving anti-CGRP mAbs. Methods We included the demographic characteristics, effectiveness—reduction in the number of monthly headache days (MHD) and monthly migraine days (MMD), 30%, 50%, and 75% responder rates—and treatment emergent adverse events (TEAEs). The primary endpoint was the 50% response rate regarding MHD at weeks 20–24; exploratory 50% response predictors in the elderly were evaluated. Results In total, 228 patients were included: 114 cases , 114 controls-. Among cases 84.2% (96/114) were women, 79.8% (91/114) CM; mean age of cases 70.1 years old (range: 66–86); mean age of controls was 42.9 years old(range: 38–49). Cases had a higher percentage of vascular risk factors (P  < .05),older age of onset (P  < .001) and more reported prior preventive treatments (P  < .001). Regarding effectiveness in cases, 50% response rate was achieved by 57.5% (42/73) at 20–24 weeks, with lower reduction in the MHD at 8–12 weeks (5 [7.2], 8 [9.1]; P  = .001) and a higher reduction in MMD at 20–24 weeks (10.7 [9.1], 9.2 [7.7]; P  = .04) compared to the control group. The percentage of TEAEs was similar in the 2 groups. Diagnosis of episodic migraine (EM) (P  = .03) and lower number of MHD at baseline (P  =.001) were associated with a 50% response in the elderly in univariate analysis. Conclusions Our study provides real world evidence of effectiveness and safety of anti-CGRP mAbs for migraine in patients without upper age-limit and possible predictors of anti-CGRP response in the elderly. [ABSTRACT FROM AUTHOR]

Syphilis, caused by infection with the bacterium Treponema pallidum, is a sexually transmitted infection for which incidence has been increasing since 2002, especially among adult men >55 years of age [...]

Background: Multiple sclerosis (MS) is a chronic demyelinating autoimmune disorder which may cause long-term disability. MicroRNA (miRNA) are stable, non-coding molecules that have been identified in our Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women's Hospital (CLIMB)-cohort, as well as other international cohorts, as potential disease biomarkers in MS. However, few studies have evaluated the association of miRNA expression early in the MS disease course with long-term outcomes. Therefore, we aimed to evaluate the potential role of three candidate serum miRNAs previously correlated with MS disability in patients with MS, miR-320b, miR-25-3p and miRNA 486-5p, as early biomarkers of MS disability at 10-year follow-up. Main body: We included 144 patients with serum obtained within three years of MS onset. miRNA expression was measured by RNA extraction followed by RT-PCR. Demographic, clinical, brain MRI and other biomarkers were collected. The primary outcome was the association between early miRNA expression and retaining benign MS, defined as EDSS ≤ 2 at 10-year follow-up. Among the 144 patients, 104 were benign and 40 were not benign at 10-year follow-up. 89 (62%) were women, with mean age at onset 37.7 (SD: 9.6) years. Patients who retained benign MS had lower values of miR-25-3p (p = 0.047) and higher miR-320b (p = 0.025) values. Development of SPMS was associated with higher miR-320b (p = 0.002) levels. Brain parenchymal fraction at year 10 was negatively correlated with miR-25-3p (p = 0.0004) and positively correlated with miR-320b (p = 0.006). No association was found between miR-486-5p and any outcome, and 10-year T2-lesion volume was not associated with any miRNA. Conclusions: Our results show that miR-320b and miR-25-3p expression are early biomarkers associated with MS severity and brain atrophy. This study provides class III evidence of that miR-320b and miR-25-3p are associated with long-term MS disability which may be a potential tool to risk-stratify patients with MS for early treatment decisions. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) is a disabling autoimmune demyelinating disorder affecting young people and causing significant disability. In the last decade, different microRNA (miRNA) expression patterns have been associated to several treatment response therapies such as interferon and glatiramer acetate. Nowadays, there is increasing interest in the potential role of miRNA as treatment response biomarkers to the most recent oral and intravenous treatments. In this study, we aimed to evaluate serum miRNAs as biomarkers of No Evidence of Disease Activity (NEDA-3) at 2 years in patients with relapsing remitting MS (RRMS) treated with fingolimod. Main body: A Discovery cohort of 31 RRMS patients treated with fingolimod were identified from the CLIMB study and classified as No Evidence of Disease Activity (NEDA-3) or Evidence of Disease Activity (EDA-3) after 2 years on treatment. Levels of miRNA expression were measured at 6 months using human serum miRNA panels and compared in EDA-3 and NEDA-3 groups using the Wilcoxon rank sum test. A set of differentially expressed miRNA was further validated in an independent cohort of 22 fingolimod-treated patients. We found that 548a-3p serum levels were higher levels in fingolimod-treated patients classified as NEDA-3, compared to the EDA-3 group in both the Discovery (n = 31; p = 0.04) and Validation (n = 22; p = 0.03) cohorts 6 months after treatment initiation; miR-548a-3p provided an AUC of 0.882 discriminating patients with NEDA-3 at 2 years in the Validation cohort. Conclusion: Our results show differences in miR-548a-3p expression at 6 months after fingolimod start in patients with MS with NEDA-3 at 2 years. These results provide class III evidence of the use of miR-548a-3p as biomarker of NEDA-3 in patients with fingolimod. [ABSTRACT FROM AUTHOR]

Background and purpose: The aim of our study is to review the relationship between NCSE and sCJD. Creutzfeldt–Jakob disease (CJD) is the most common form of human prion disease. Electroencephalography (EEG)‐detected changes such as periodic sharp wave complexes, superimposable to those seen in non‐convulsive epileptic status (NCSE), have only rarely been described at CJD onset, especially in sporadic CJD (sCJD) cases. Methods: We describe clinical, EEG, cerebrospinal fluid (CSF) and neuroimaging findings of a confirmed case of sCJD with tau pathology, initially diagnosed as NCSE. We performed a literature review in PubMed of previous publications on both sCJD and NCSE. Results: An 82‐year‐old woman with no medical history presented with a 2‐week rapidly progressive neurological disorder, with motor aphasia, myoclonus, pyramidalism, and left posterior alien hand. EEG showed periodic sharp waves on right frontal regions, so anti‐epileptic treatment was started. CSF results were normal. Brain magnetic resonance imaging demonstrated hyperintensity of the right cerebral cortex in diffusion sequences. Due to suspected new‐onset refractory status epilepticus (NORSE), corticosteroid treatment was started, without clinical improvement. Necropsy results confirmed sCJD with tau pathology. The literature review identified 14 references including a total of 18 cases with NCSE as the presenting symptom of sCJD; the clinical and results in complementary tests were compiled into a table. Conclusions: Sporadic CJD should be considered in the differential diagnosis of patients with rapid cognitive decline and EEG changes consistent with NCSE. The wide heterogeneity in the etiology of NCSE, including autoimmune disorders, especially NORSE, suggests immunotherapy should be initiated based on a good risk–benefit balance. Some cases of sCJD, such as the present case with tau pathology, may mimic this clinico‐electrical course. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to analyze the potential association between personality traits and onabotulinumtoxin A (onabotA) response in patients with chronic migraine (CM). Background: Previous studies from a categorial perspective show that patients with CM have anxious or obsessive personality according to the Salamanca screening test. However, the influence of personality traits in onabotA response in patients with CM has not yet been studied. We hypothesize that cluster C personality traits may be associated with non‐response to onabotA. Methods: This case‐control observational study includes patients with CM who received at least 2 treatment cycles of onabotA in 2 headache units between January and May 2018. onabotA response was defined as a reduction of at least 50% in the number of monthly migraine days. Personality traits were evaluated using the Salamanca questionnaire, a validated categorial inventory assessing 11 personality traits. Results: One hundred and twelve patients, 100/112 (89.6%) females, mean age (standard deviation): 43 (11) years, were recruited. 96/112 (85.7%) achieved response to onabotA. Dependent trait was significantly associated with non‐response to onabotA (P =.008; OR: 0.223 [95%CI: 0.074 to 0.675]). Significant association with other personality traits or confounders was not found. Conclusions: To the best of our knowledge, this is the first study showing personality traits may predict onabotA response in patients with CM. The presence of dependent personality trait in patients with CM is associated with non‐response to onabotA. [ABSTRACT FROM AUTHOR]

Background: Occipital nerve stimulation (ONS) is a treatment with evidence in refractory chronic cluster headache (CCH). However, the variable response rate and cost make it necessary to investigate predictors of response. Methods: This is a cross-sectional study conducted through the review of medical records of CCH patients from six hospitals in Madrid. Epidemiological and clinical variables were compared between patients with ONS failure and the rest. ONS failure was defined as the need for device withdrawal or switch off because of lack of response or adverse events. Results: From a series of 88 CCH, 26 (29.6%) underwent ONS surgery, of whom 13/26 (50.0%) failed because lack of response. ONS failure group had an earlier headache onset (mean ± SD) of 27.7 ± 6.9 vs. 36.7 ± 11.8 years, p = 0.026) and a higher smoking rate (100% vs. 42.9%, p = 0.006). Stational fluctuations (58.3% vs. 7.7%, p = 0.007) and nocturnal exacerbations (91.7% vs. 53.9%, p = 0.035) were more frequent in the ONS failure group as well. There was no difference between groups in diagnostic delay, years of evolution prior to surgery, mental illness, comorbidity with other headache disorders or chronic pain conditions or prior response to occipital nerves anesthetic blocks. Conclusions: Some clinical features such as an early debut, smoking and seasonal or circadian fluctuations could be related to failure of ONS in refractory CCH. [ABSTRACT FROM AUTHOR]