Clinical predictors of therapeutic failure of occipital nerve stimulation in refractory chronic cluster headache.

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.

The profile of refractory chronic cluster headache.

INTRODUCTION: Chronic cluster headache (CCH) is a relatively rare primary headache disorder whose management is often challenging. The prevalence of refractory CCH (rCCH) is unknown. Our aim is to describe the frequency of rCCH within a population of CCH, define the clinical profile of the refractory patients and the treatments they underwent. METHODS: We conducted a cross-sectional study through a review of the medical records of CCH patients in six hospitals in Madrid, Spain. Data on epidemiological, clinical presentation, treatment and disease activity at the moment were collected. The European Headache Federation diagnostic criteria were used for rCCH definition. High disease activity was defined as having at least 3 severe attacks per week that impact quality of life despite treatment. Non-rCCH and rCCH groups were compared. RESULTS: 88 CCH patients were analyzed, 68.2% (60/88) met rCCH criteria at some point in their evolution. A longer diagnostic delay (4.6 ± 7.1 vs. 3.2 ± 3.7 years, p = 0.017) was observed in rCCH. All rCCH patients tried therapies without established evidence from randomized clinical trials. OnabotulinumtoxinA and galcanezumab were initiated in 77.3% (68/88) and 5.7% (5/88), but discontinued in 52.9% (36/68) and 60.0% (3/5), respectively. Occipital nerve stimulation (ONS) was implanted in 29.6% (26/88), with 50.0% (13/26) still active. Other treatment options are described and discussed. Despite treatment, 60.2% (53/88) still have high disease activity. CONCLUSION: CCH is a disorder with poor prognosis, meeting refractoriness criteria in more than half. OnabotulinumtoxinA and ONS could be the effective in refractory patients.

Epicranial headaches part 2: Nummular headache and epicrania fugax.

BACKGROUND: Nummular headache and epicrania fugax are two primary headaches that fall under the heading of epicranial headaches. METHODS: This article reviews the epidemiological and clinical features of nummular headache and epicrania fugax, proposed pathogenic mechanisms and state-of-the-art management, according to the literature. RESULTS AND CONCLUSIONS: Nummular headache and epicrania fugax are generally viewed as rare headache disorders, but no population-based epidemiological data are available. Nummular headache is characterized by continuous or intermittent head pain, which remains circumscribed in a round or oval area of the scalp, typically one to six centimeters in diameter. Epicrania fugax manifests with brief paroxysms of pain that move along the surface of the head, following a linear or zigzag trajectory through different nerve territories. Nummular headache and epicrania fugax are mostly primary headaches, but some secondary cases have been reported. The pathogenesis of these headaches is not fully understood. Nummular headache could probably originate in epicranial tissues or adjacent intracranial structures, while the origin of epicrania fugax could be extracranial or intracranial. Diagnostic assessment requires careful examination of the symptomatic areas. Underlying disorders should be excluded by additional investigations, including neuroimaging and appropriate blood tests. No controlled clinical trials have been conducted in nummular headache or epicrania fugax. Analgesics and anti-inflammatory drugs, botulinum toxin and gabapentin are currently the most recommended treatment options for nummular headache. In epicrania fugax, the most used treatments are gabapentin, lamotrigine, and other antiseizure medications.

Nummular headache responsive to anti-calcitonin gene-related peptide monoclonal antibodies in a patient with migraine.

BACKGROUND: Nummular headache (NH) is defined by the presence of localized pain circumscribed to a round or elliptical area of the scalp, with a well-defined contour and a diameter of 1-6 cm. Although some evidence supports a peripheral mechanism, its etiopathogenesis remains unclear. CASE: We report the case of a 64-year-old man with high-frequency episodic migraine who has used topiramate, beta-blockers, flunarizine, and amitriptyline without effect. In the last 8 years he also had continuous pain in an oval area of the scalp, consistent with NH. Triptans were ineffective for this new pain, and preventive therapy with gabapentin and onabotulinumtoxinA in the painful area had no effect. NH remitted when the patient received monthly treatment with subcutaneous galcanezumab for his migraine. CONCLUSIONS: Monoclonal antibodies against calcitonin gene-related peptide (CGRP), in particular galcanezumab, might be an effective therapy in some patients with NH. CGRP may have a role in the etiopathogenesis of this headache, which warrants further investigation.

Headache as a COVID-19 onset symptom and post-COVID-19 symptom in hospitalized COVID-19 survivors infected with the Wuhan, Alpha, or Delta SARS-CoV-2 variants.

OBJECTIVE: This study looked at differences in the presence of headache as an onset symptom of coronavirus disease 2019 (COVID-19) and as a post-COVID-19 symptom in individuals previously hospitalized owing to infection with the Wuhan, Alpha, or Delta variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). BACKGROUND: Headache can be present in up to 50% of individuals during the acute phase of SARS-CoV-2 infection and in 10% of subjects during the post-COVID-19 phase. There are no data on differences in the occurrence of headache in the acute- and post-COVID-19 phase according to the SARS-CoV-2 variants. METHODS: A cross-sectional cohort study was conducted. Unvaccinated subjects previously hospitalized for COVID-19 caused by the Wuhan (n = 201), Alpha (n = 211), or Delta (n = 202) SARS-CoV-2 variants were scheduled for a telephone interview 6 months after hospital discharge. Hospitalization data were collected from hospital medical records. RESULTS: The presence of headache as a COVID-19 onset symptom at hospitalization was higher in subjects with the Delta variant (66/202, 32.7%) than in those infected with the Wuhan (42/201, 20.9%; odds ratio [OR] 1.83, 95% confidence interval [CI] 1.17-2.88) or Alpha (25/211, 11.8%; OR 3.61, 95% CI, 2.16-6.01) variants. The prevalence of post-COVID-19 headache 6 months after hospital discharge was higher in individuals infected with the Delta variant (26/202, 12.9%) than in those infected with the Wuhan (11/201, 5.5%; OR 2.52, 95% CI 1.22-5.31) or Alpha (eight of 211, 3.8%; OR 3.74, 95% CI 1.65-8.49) variants. The presence of headache as a COVID-19 onset symptom was associated with post-COVID-19 headache in subjects infected with the Wuhan (OR 7.75, 95% CI 2.15-27.93) and Delta variants (OR 2.78, 95% CI 1.20-6.42) but not with the Alpha variant (OR 2.60, 95% CI 0.49-13.69). CONCLUSION: Headache was a common symptom in both the acute- and post-COVID-19 phase in subjects infected with the Wuhan, Alpha, and Delta variants but mostly in those infected with the Delta variant.

Sensory processing and adaptive behavior in Phelan-McDermid syndrome: a cross-sectional study.

Phelan-McDermid syndrome (PMS) is a genetic disorder caused by a mutation or deletion of the SHANK3 gene (chromosome 22q13.3), characterized by different sensory processing anomalies. The objective of this study is to expand and provide a detailed definition of the sensory profile of patients with PMS. The secondary objective was to examine the relationship between sensory patterns and adaptive behavior. A cross-sectional study was carried out among 51 Spanish patients with a confirmed genetic diagnosis of PMS. All the participants' parents completed the Short Sensory Profile-Spanish (SSP-S) and the Adaptive Behavior Assessment System II (ABAS-II). Correlational, multiple regression and hierarchical cluster analyses were performed. An atypical sensory profile was identified in almost 75% of PMS patients. Definite differences were found among scores; nonetheless, sub-threshold values were observed in tactile sensitivity, underresponsive/seeks sensation, auditory filtering, and low energy/weak sensory categories. Conceptual, social, and practical domains, as well as the General Adaptive Composite (GAC) of the ABAS-II showed extremely low scores (i.e., <70). Significant correlations were found (p<0.005) between SSP-S scores and the conceptual, social, practical, and GAC index of the ABAS-II, whereby higher SSP-S scores were associated with better skills and higher adaptive performance. The cluster analysis indicated that the group with the largest mutation size (7.23 Mb) showed the greatest sensory processing difficulties and very low adaptive skills. CONCLUSIONS: Patients with PMS show an atypical sensory profile, which correlates with limitations in general adaptive behaviors. WHAT IS KNOWN: • PMS sensory processing difficulties were associated with a pattern of underresponsive/seeks sensation, low energy/weak, and tactile hyporeactivity. • Sensory processing difficulties have been associated with limitations in the development of appropriate adaptive communication and interaction behaviors. WHAT IS NEW: • Sensory definite differences associated with tactile hyperreactivity, as well as significant effects of underresponsiveness/seeks sensation and auditory filtering categories on the adaptive abilities were found in SHANK3deletion patients. • Cluster analysis suggests that smaller mutation sizes were related to better sensory processing and higher adaptive skills, while patients with larger deletion sizes have greater adaptive difficulties and worse sensory processing skills.

Fatigue and Dyspnoea as Main Persistent Post-COVID-19 Symptoms in Previously Hospitalized Patients: Related Functional Limitations and Disability.

BACKGROUND: Multicentre studies focussing on specific long-term post-COVID-19 symptoms are scarce. OBJECTIVE: The aim of this study was to determine the levels of fatigue and dyspnoea, repercussions on daily life activities, and risk factors associated with fatigue or dyspnoea in COVID-19 survivors at long term after hospital discharge. METHODS: Age, gender, height, weight, symptoms at hospitalization, pre-existing medical comorbidity, intensive care unit admission, and the presence of cardio-respiratory symptoms developed after severe acute respiratory syndrome coronavirus 2 infection were collected from patients who recovered from COVID-19 at 4 hospitals in Madrid (Spain) from March 1 to May 31, 2020 (first COVID-19 wave). The Functional Impairment Checklist was used for evaluating fatigue/dyspnoea levels and functional limitations. RESULTS: A total of 1,142 patients (48% women, age: 61, standard deviation [SD]: 17 years) were assessed 7.0 months (SD 0.6) after hospitalization. Fatigue was present in 61% patients, dyspnoea with activity in 55%, and dyspnoea at rest in 23.5%. Only 355 (31.1%) patients did not exhibit fatigue and/or dyspnoea 7 months after hospitalization. Forty-five per cent reported functional limitations with daily living activities. Risk factors associated with fatigue and dyspnoea included female gender, number of pre-existing comorbidities, and number of symptoms at hospitalization. The number of days at hospital was a risk factor just for dyspnoea. CONCLUSIONS: Fatigue and/or dyspnoea were present in 70% of hospitalized COVID-19 survivors 7 months after discharge. In addition, 45% patients exhibited limitations on daily living activities. Being female, higher number of pre-existing medical comorbidities and number of symptoms at hospitalization were risk factors associated to fatigue/dyspnoea in COVID-19 survivors 7 months after hospitalization.

Thrombotic microangiopathy in untreated myeloma patients receiving carfilzomib, cyclophosphamide and dexamethasone on the CARDAMON study.

Proteasome inhibitors have been associated with thrombotic microangiopathy (TMA) - a group of disorders characterised by occlusive microvascular thrombosis causing microangiopathic haemolytic anaemia, thrombocytopenia and end-organ damage. To date, carfilzomib-associated TMA has predominantly been described in relapsed/refractory myeloma patients. We report eight patients with newly diagnosed myeloma who experienced TMA events while receiving carfilzomib on the phase II CARDAMON trial. The first three occurred during maintenance single-agent carfilzomib, two occurred at induction with carfilzomib given with cyclophosphamide and dexamethasone (KCd) and three occurred during KCd consolidation. At TMA presentation 6/8 were hypertensive; 7/8 had acute kidney injury and in three, renal impairment persisted after resolution of TMA in other respects. The mechanism of carfilzomib-associated TMA remains unclear, though patients with known hypertension seem particularly susceptible. Given the first three cases occurred during maintenance after a longer than five-week treatment break, a protocol amendment was instituted with: aggressive hypertension management, carfilzomib step-up dosing (20 mg/m2 on day 1) at start of maintenance before dose escalation to 56 mg/m2 maximum, and adding 10 mg dexamethasone as premedication to maintenance carfilzomib infusions. No further TMA events occurred during maintenance following this amendment and the TMA incidence reduced from 4·2 to 1·6 per 1 000 patient cycles.

The presence of headache at onset in SARS-CoV-2 infection is associated with long-term post-COVID headache and fatigue: A case-control study.

OBJECTIVE: To investigate the association of headache during the acute phase of SARS-CoV-2 infection with long-term post-COVID headache and other post-COVID symptoms in hospitalised survivors. METHODS: A case-control study including patients hospitalised during the first wave of the pandemic in Spain was conducted. Patients reporting headache as a symptom during the acute phase and age- and sex-matched patients without headache during the acute phase participated. Hospitalisation and clinical data were collected from medical records. Patients were scheduled for a telephone interview 7 months after hospital discharge. Participants were asked about a list of post-COVID symptoms and were also invited to report any additional symptom they might have. Anxiety/depressive symptoms and sleep quality were assessed with the Hospital Anxiety and Depression Scale and the Pittsburgh Sleep Quality Index. RESULTS: Overall, 205 patients reporting headache and 410 patients without headache at hospitalisation were assessed 7.3 months (Standard Deviation 0.6) after hospital discharge. Patients with headache at onset presented a higher number of post-COVID symptoms (Incident Rate Ratio: 1.16, 95% CI: 1.03-1.30). Headache at onset was associated with a previous history of migraine (Odd Ratio: 2.90, 95% Confidence Interval: 1.41-5.98) and with the development of persistent tension-type like headache as a new post-COVID symptom (Odd Ratio: 2.65, 95% CI: 1.66-4.24). Fatigue as a long-term symptom was also more prevalent in patients with headache at onset (Odd Ratio: 1.55, 95% CI: 1.07-2.24). No between-group differences in the prevalence of anxiety/depressive symptoms or sleep quality were seen. CONCLUSION: Headache in the acute phase of SARS-CoV-2 infection was associated with higher prevalence of headache and fatigue as long-term post-COVID symptoms. Monitoring headache during the acute phase could help to identify patients at risk of developing long-term post-COVID symptoms, including post-COVID headache.

Headache as an acute and post-COVID-19 symptom in COVID-19 survivors: A meta-analysis of the current literature.

BACKGROUND: Headache is identified as a common post-COVID sequela experienced by COVID-19 survivors. The aim of this pooled analysis was to synthesize the prevalence of post-COVID headache in hospitalized and non-hospitalized patients recovering from SARS-CoV-2 infection. METHODS: MEDLINE, CINAHL, PubMed, EMBASE, and Web of Science databases, as well as medRxiv and bioRxiv preprint servers, were searched up to 31 May 2021. Studies or preprints providing data on post-COVID headache were included. The methodological quality of the studies was assessed using the Newcastle-Ottawa Scale. Random effects models were used for meta-analytical pooled prevalence of post-COVID headache. Data synthesis was categorized at hospital admission/symptoms' onset, and at 30, 60, 90, and ≥180 days afterwards. RESULTS: From 9573 studies identified, 28 peer-reviewed studies and 7 preprints were included. The sample was 28,438 COVID-19 survivors (12,307 females; mean age: 46.6, SD: 17.45 years). The methodological quality was high in 45% of the studies. The overall prevalence of post-COVID headache was 47.1% (95% CI 35.8-58.6) at onset or hospital admission, 10.2% (95% CI 5.4-18.5) at 30 days, 16.5% (95% CI 5.6-39.7) at 60 days, 10.6% (95% CI 4.7-22.3) at 90 days, and 8.4% (95% CI 4.6-14.8) at ≥180 days after onset/hospital discharge. Headache as a symptom at the acute phase was more prevalent in non-hospitalized (57.97%) than in hospitalized (31.11%) patients. Time trend analysis showed a decreased prevalence from the acute symptoms' onset to all post-COVID follow-up periods which was maintained afterwards. CONCLUSION: This meta-analysis found that the prevalence of post-COVID headache ranged from 8% to 15% during the first 6 months after SARS-CoV-2 infection.

The global antiphospholipid syndrome score in women with systemic lupus erythematosus and adverse pregnancy outcomes.

OBJECTIVES: To validate the global antiphospholipid syndrome score (GAPSS) in a cohort of women with systemic lupus erythematosus (SLE) and antiphospholipid antibodies (aPL). METHODS: This retrospective study included 143 women ever pregnant with SLE who presented in our outpatient clinic were included. Data on cardiovascular risk factors and aPL status were retrospectively collected and their individual GAPSS score was calculated. RESULTS: Significantly higher GAPSS values were found in women with any placental medicated complication (such as foetal death, placental abruption, prematurity, pre-eclampsia or intrauterine growth restriction (IUGR)) (GAPSS 8.2±3.0 vs. 3.5±3.0, p<0.001). Significantly higher GAPSS values were also found in those with recurrent miscarriages (RM) <10 weeks, foetal death, placental abruption, prematurity, pre-eclampsia or IUGR) (GAPSS 8.3±4.5 vs. 3.2±2.6, p<0.001). Patients with 3 or more consecutive early miscarriages (<10 weeks), foetal death, miscarriage <10 weeks' gestation, premature birth (<34 weeks), pre-eclampsia (<34 weeks), stillbirth, and placental infarction had significantly higher GAPSS values compared to those without previous pregnancy complications. The odds ratio of having any pregnancy morbidity when having a GAPSS value ≥8 was 20 compared to those with a GAPSS of ≤1 (p<0.001). CONCLUSIONS: Women with a history of aPL-related pregnancy complications had higher GAPSS values in this retrospective cohort compared to women without pregnancy complications. This study is the first step to assess the clinical utility of the GAPSS score in pregnancy. A prospective validation is needed.

Therapy delay in status epilepticus extends its duration and worsens its prognosis.

BACKGROUND: Timing in status epilepticus (SE) attention is probably the most relevant modifiable prognostic factor and may influence SE duration and prognosis. We aimed to describe the precise relationship between management timing, duration, and prognosis of SE. METHODS: Observational longitudinal prospective study on a cohort of all patients diagnosed with SE admitted to our tertiary hospital from September 2017 to August 2019, with a 3-month follow-up. Univariate and multivariable analyses were performed to identify clinical and timing variables associated with SE duration and prognosis. RESULTS: Eighty-three SE affecting 76 patients were included. Median age was 73 years, 61.4% were women, median baseline modified Rankin Scale (mRS) was 2, and 55.4% had prior epilepsy. In the out-of-hospital group (n = 50), median time to emergencies was 1.3 h and to hospital admission 2.8 h. In the global series, median time to neurologist was 4.3 h, and median time to therapy initiation was 4.5 h. These four times positively correlated with SE duration (all Spearman's rho coefficient >0.5, all p < .001). SE median duration was 24 h and was extended 1.2 h for each hour of treatment delay. A longer SE duration was associated with increased mortality and morbidity, both at hospital discharge and at 3-month follow-up (both p < .05). After 3 months, mortality was 30.1%, while recovery to baseline mRS occurred in 39.5%, with an overall median mRS of 4. CONCLUSIONS: There were pervasive delays in all phases of SE attention, which conditioned a longer SE duration, and this led to increased long-term morbimortality.

Epidaily, a scale for comprehensive functional assessment of patients with epilepsy.

OBJECTIVE: To develop and validate an epilepsy-specific scale for comprehensive functional assessment of patients with epilepsy, named Epidaily. METHODS: The multidisciplinary research group created through brainstorming a list of 47 items to explore the cognitive, social, basic and instrumental functionality of the patient. A group of epilepsy experts independent of the research group evaluated the suitability of all the items, which then were selected and reviewed by the research group to conform the Epidaily scale. On a sample of 102 patients, a reliability analysis was performed, as well as a validation one using as reference scale the score on the Activities of Daily Living Questionnaire (ADLQ), which evaluates basic and instrumental functionality. RESULTS: Epidaily consisted of 10 items distributed in four dimensions, with a possible score from 0 to 100 (perfect functionality). Inter-observer reliability was excellent, with an intraclass correlation coefficient of 0.98 (95% confidence interval 0.97-0.99). Criterion validity was demonstrated by the high positive correlation of the Epidaily score with the ADLQ score (Spearman's rho coefficient 0.85, p < 0.001). Significant relation was found between ADLQ and Epidaily in the linear regression analysis (p < 001), which reported that Epidaily explains 85.5% of the variability of ADLQ (R-squared 0.85). Discriminant validity was also proved, as Epidaily allowed to classify epilepsy severity based on Cramer et al epilepsy severity classification. The median time to obtain the Epidaily score was 5 min (interquartile range 4-6). SIGNIFICANCE: Epidaily is a brief and versatile scale, with excellent inter-observer reliability, which has been validated for comprehensive functional assessment of patients with epilepsy.

Predictors of recovery following allogeneic CD34+-selected cell infusion without conditioning to correct poor graft function.

Poor graft function is a serious complication following allogeneic hematopoietic stem cell transplantation. Infusion of CD34+-selected stem cells without pre-conditioning has been used to correct poor graft function, but predictors of recovery are unclear. We report the outcome of 62 consecutive patients who had primary or secondary poor graft function who underwent a CD34+-selected stem cell infusion from the same donor without further conditioning. Forty-seven of 62 patients showed hematological improvement and became permanently transfusion and growth factor-independent. In multivariate analysis, parameters significantly associated with recovery were shared CMV seronegative status for recipient/donor, the absence of active infection and matched recipient/donor sex. Recovery was similar in patients with mixed and full donor chimerism. Five -year overall survival was 74.4% (95% CI 59-89) in patients demonstrating complete recovery, 16.7% (95% CI 3-46) in patients with partial recovery and 22.2% (CI 95% 5-47) in patients with no response. In patients with count recovery, those with poor graft function in 1-2 lineages had superior 5-year overall survival (93.8%, 95% CI 82-99) than those with tri-lineage failure (53%, 95% CI 34-88). New strategies including cytokine or agonist support, or second transplant need to be investigated in patients who do not recover.

Paroxysmal headache with extracephalic irradiation: Proposal for a new variant of epicrania fugax in a series of five patients.

BACKGROUND: Epicrania fugax consists of brief paroxysms of pain, which radiate in a line or in zigzag trajectory across the surface of the scalp or the face. METHODS: A prospective, descriptive study was performed in five patients presenting with an epicrania fugax-type pain with extracephalic irradiation. RESULTS: All patients were women, and the mean age at onset was 59.8 (standard deviation, 10.9). They had unilateral paroxysms of electrical pain starting at a particular point in the head (parietal, n = 3; vertex, n = 1; frontal, n = 1) and rapidly radiating downwards in a lineal trajectory to reach extracephalic regions (ipsilateral limbs, n = 2; shoulder, n = 2; low neck, n = 1) in 1-3 seconds. Pain intensity was moderate or severe. Three patients had nummular headache at the point where the paroxysms originated. One patient had spontaneous remission, and four patients achieved complete or almost complete response with therapy (onabotulinumtoxinA, n = 2; indomethacin, n = 1; amitriptyline, n = 1; lamotrigine, n = 1). CONCLUSION: The spectrum of epicrania fugax may include paroxysms with extracephalic irradiation. The propagation of pain beyond the head and the face supports the involvement of central mechanisms in the pathophysiology of this entity.

16th International Congress on Antiphospholipid Antibodies Task Force Report on Antiphospholipid Syndrome Treatment Trends.

Antiphospholipid syndrome (APS), an acquired autoimmune thrombophilia, is characterised by thrombosis and/or pregnancy morbidity in association with persistent antiphospholipid antibodies. The 16th International Congress on Antiphospholipid Antibodies Task Force on APS Treatment Trends reviewed the current status with regard to existing and novel treatment trends for APS, which is the focus of this Task Force report. The report addresses current treatments and developments since the last report, on the use of direct oral anticoagulants in patients with APS, antiplatelet agents, adjunctive therapies (hydroxychloroquine, statins and vitamin D), targeted treatment including rituximab, belimumab, and anti-TNF agents, complement inhibition and drugs based on peptides of beta-2-glycoprotein I. In addition, the report summarises potential new players, including coenzyme Q10, adenosine receptor agonists and adenosine potentiation. In each case, the report provides recommendations for clinicians, based on the current state of the art, and suggests a clinical research agenda. The initiation and development of appropriate clinical studies requires a focus on devising suitable outcome measures, including a disease activity index, an optimal damage index, and a specific quality of life index.

The Day My Life Changed: A Qualitative Study of the Experiences of Patients With New Daily Persistent Headache.

OBJECTIVES: This study aimed to explore the views and experiences of a group of Spanish patients suffering from new daily persistent headache (NDPH). METHODS: A qualitative descriptive study was conducted with patients diagnosed with NDPH. Purposeful sampling was performed among patients attending a specialized Headache Unit at 2 university hospitals between February 2017 and December 2018. In total, 18 patients (11 women, 7 men; mean age 45.3, standard deviation 10.6) with a median duration of illness of 70 months (interquartile range, 24-219) were recruited to this study. Data were collected through in-depth interviews, researchers' field notes and patients' drawings. Thematic analysis was used to identify emerging themes. RESULTS: Three main themes were identified: (1) the origin of the illness and seeking answers; (2) characteristics of the pain; and (3) the impact of pain on patients' lives. The patients precisely recalled the time of onset and the trigger of the pain. Pain was constantly present, although it varied in form. At the onset, pain was perceived as a sign of alarm while, over time, it became an invisible illness. The headache commonly had a major impact on everyday life and could cause lifestyle changes. In addition, pain could be emotionally disruptive and could also lead to family estrangement and a search for solitude. CONCLUSIONS: Our results provide insight into how NDPH is experienced, which may be helpful in managing NDPH patients. In our cohort, patients identified precipitating events but sought answers regarding the origin of their illness and their pain. Pain was a continuous sensation that had a major impact on patients' daily lives and emotions.

Transcutaneous Supraorbital Stimulation as a Preventive Treatment for Chronic Migraine: A Prospective, Open-Label Study.

BACKGROUND AND OBJECTIVE: Successful preventive treatment in chronic migraine (CM) remains an unmet need in some cases, and new therapeutic strategies are emerging. We aimed to test the effect of noninvasive, transcutaneous supraorbital nerve stimulation (tSNS) in a group of patients with CM. PATIENTS AND METHODS: This was an open label, quasi-experimental design. Twenty-five CM patients were recruited from two hospital headache clinics. After a one-month baseline period, monthly visits were scheduled during three months. Headache occurrence, its intensity, and symptomatic medication intake were recorded through a diary kept by each patient. Both a per-protocol analysis and an intention-to-treat analysis were performed for the main outcome measures. RESULTS: Twenty-one and 24 patients were included in the per-protocol and the intention-to-treat analyses, respectively. In the per-protocol analysis, a significant four-day decrease in the mean monthly days with moderate or severe headache was observed from baseline to the end of the study (t test, P = 0.0163), and there was a nonsignificant reduction of 2.95 in the mean monthly total headache days. In the intention-to-treat analysis, a nonsignificant 3.37 reduction in the mean monthly days with moderate or severe headache was observed for the same period, and there was a significant 2.75 reduction in the mean monthly days with any headache (t test, P = 0.016). CONCLUSIONS: tSNS could hold preventive properties in the treatment of CM, but the effect may be either mild or controversial. Double blind, sham-controlled studies are essential to confirm these findings and to outline their clinical relevance in the CM therapeutic scenario.

Widespread Hypersensitivity to Pressure Pain in Men With Cluster Headache During Prolonged Remission Is Not Related to the Levels of Depression and Anxiety.

BACKGROUND: Diminished pressure pain thresholds (PPTs) have been found in patients with cluster headache (CH), suggesting the presence of central sensitization. However, it is not known whether sensitization persists over time during the asymptomatic periods. OBJECTIVE: To investigate if men with episodic CH in a long-lasting remission phase exhibit widespread pressure pain hypersensitivity. METHODS: Forty men with episodic CH and 40 matched controls were enrolled. PPTs were assessed bilaterally over 1 trigeminal (temporalis muscle) and 3 extra-trigeminal points (C5/C6 zygapophyseal joint, second metacarpal, tibialis anterior muscle) by a blinded assessor. Patients were assessed in a prolonged remission phase, at least 6 months after their last CH attack and without taking any medication. Depression and anxiety levels were assessed with the Hospital Anxiety and Depression Scale (HADS). For each point, differences in PPTs were evaluated with a multivariate mixed-model analysis of covariance test, with side and group as main factors and depression and anxiety levels as covariates. RESULTS: PPTs were significantly decreased bilaterally over the temporalis muscle (mean difference: 85 to 100 kPa), C5/C6 zygapophyseal joint (mean difference: 65 to 80 kPa), second metacarpal (mean difference: 65 to 90 kPa), and tibialis anterior muscle (mean difference: 135 to 155 kPa) in patients with CH when compared to headache-free subjects (all, P < 0.001). No effect of anxiety or depression levels was found. CONCLUSIONS: Patients with CH exhibited bilateral widespread hypersensitivity to pressure pain during long-lasting remission periods, which was not associated with depression or anxiety. These results support the persistence of central sensitization in episodic CH, even in remote asymptomatic phases.

EULAR recommendations for the management of antiphospholipid syndrome in adults.

The objective was to develop evidence-based recommendations for the management of antiphospholipid syndrome (APS) in adults. Based on evidence from a systematic literature review and expert opinion, overarching principles and recommendations were formulated and voted. High-risk antiphospholipid antibody (aPL) profile is associated with greater risk for thrombotic and obstetric APS. Risk modification includes screening for and management of cardiovascular and venous thrombosis risk factors, patient education about treatment adherence, and lifestyle counselling. Low-dose aspirin (LDA) is recommended for asymptomatic aPL carriers, patients with systemic lupus erythematosus without prior thrombotic or obstetric APS, and non-pregnant women with a history of obstetric APS only, all with high-risk aPL profiles. Patients with APS and first unprovoked venous thrombosis should receive long-term treatment with vitamin K antagonists (VKA) with a target international normalised ratio (INR) of 2-3. In patients with APS with first arterial thrombosis, treatment with VKA with INR 2-3 or INR 3-4 is recommended, considering the individual's bleeding/thrombosis risk. Rivaroxaban should not be used in patients with APS with triple aPL positivity. For patients with recurrent arterial or venous thrombosis despite adequate treatment, addition of LDA, increase of INR target to 3-4 or switch to low molecular weight heparin may be considered. In women with prior obstetric APS, combination treatment with LDA and prophylactic dosage heparin during pregnancy is recommended. In patients with recurrent pregnancy complications, increase of heparin to therapeutic dose, addition of hydroxychloroquine or addition of low-dose prednisolone in the first trimester may be considered. These recommendations aim to guide treatment in adults with APS. High-quality evidence is limited, indicating a need for more research.