Understanding the diagnoses and medical care experience of patients with new daily persistent headache: a qualitative study in Spain.

OBJECTIVE: To explore the experiences of patients suffering from new daily persistent headache (NDPH) regarding the diagnostic process, treatment and medical care. DESIGN: A qualitative phenomenological study was conducted. SETTING: A specialised headache unit at two university hospitals in Spain between February 2017 and December 2018. PARTICIPANTS: Patients diagnosed with NDPH according to the International Classification of Headache disorders (third beta edition). METHODS: Purposeful sampling was performed. Data were collected using unstructured and semistructured interviews, researchers' field notes and patients' drawings. An inductive thematic analysis was used to identify significant emerging themes from interviews, field notes and descriptions of patients' drawings. Also, Guillemin's proposal was used to analyse the contents of drawings. RESULTS: Nineteen patients with a mean age of 45.3 were recruited. Four main themes emerged: (1) Seeking a diagnosis, patients visit many doctors without receiving a clear answer and their diagnosis is delayed; (2) Self-medication-minimising pill intake, medication is ineffective, and therefore, some patients discontinue treatment, or are flexible with how they take medication; (3) Trying other non-pharmacological options, many patients turn to other therapies and complementary and/or alternative therapies as a second option, however these are ineffective and (4) Medical care, with two subthemes, referrals and lacking continuity of care, and building the doctor-patient relationship. Patients describe how the referral breaks the continuity of care, and how they identify the traits of a doctor who is approachable and which behaviours the doctor should avoid when caring for patients. CONCLUSIONS: An in-depth knowledge of the beliefs and expectations of patients with NDPH will allow the professional to establish a relationship of trust, which will improve the patients' knowledge of which therapies are the most appropriate, and to establish expectations based on the relationship with the doctor, and not only on patients' beliefs.

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.

Ubiquinol Effects on Antiphospholipid Syndrome Prothrombotic Profile: A Randomized, Placebo-Controlled Trial.

OBJECTIVE: Antiphospholipid syndrome (APS) leukocytes exhibit an oxidative perturbation, directly linked to alterations in mitochondrial dynamics and metabolism. This disturbance is related to the patients' prothrombotic status and can be prevented by in vitro treatment with coenzyme Q10. Our aim was to investigate short-term effects of in vivo ubiquinol (reduced coenzyme Q10 [Qred]) supplementation on markers related to inflammation and thrombosis in APS through a prospective, randomized, crossover, placebo-controlled trial. APPROACH AND RESULTS: Thirty-six patients with APS were randomized to receive Qred (200 mg/d) or placebo for 1 month. Thirty-three patients with APS completed the intervention, which increased plasma coenzyme Q10. Qred improved endothelial function and decreased monocyte expression of prothrombotic and proinflammatory mediators, inhibited phosphorylation of thrombosis-related protein kinases, and decreased peroxides and percentage of monocytes with depolarized mitochondria; mitochondrial size was increased, and mitochondrial biogenesis-related genes were upregulated. Qred ameliorated extruded neutrophil extracellular traps in neutrophils and downregulated peroxides, intracellular elastase, and myeloperoxidase. Nanostring microRNA profiling revealed 20 microRNAs reduced in APS monocytes, and 16 of them, with a preponderance of cardiovascular disease-related target mRNAs, were upregulated. Monocytes gene profiling showed differential expression of 29 atherosclerosis-related genes, 23 of them changed by Qred. Interaction networks of genes and microRNAs were identified. Correlation studies demonstrated co-ordinated effects of Qred on thrombosis and endothelial function-associated molecules. CONCLUSIONS: Our results highlight the potential of Qred to modulate the overexpression of inflammatory and thrombotic risk markers in APS. Because of the absence of clinically significant side effects and its potential therapeutic benefits, Qred might act as safe adjunct to standard therapies in APS. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02218476.

Physical therapy for headaches.

Background Headache is the medical problem most commonly observed by neurologists. Non-pharmacological treatments are commonly demanded by individuals with headaches, but their evidence of effectiveness is conflicting. Aim The current review provides an updated discussion on what is supported by current scientific evidence about physical therapies for tension-type headache (TTH), migraine, and cervicogenic headache (CeH), and which gaps there still may be in our understanding of the interventions. Methods PubMed, MEDLINE, EMBASE, AMED, CINAHL, EBSCO, Cochrane Database of Systematic Reviews, Cochrane Collaboration Trials Register, PEDro, and SCOPUS were searched from their inception through March 2015. Results/Discussion Several physical therapies including spinal joint manipulation/mobilization, soft tissue interventions, therapeutic exercises and needling therapies are proposed to be effective for the management of headaches. Current evidence has shown that the effectiveness of these interventions will depend on proper clinical reasoning since not all interventions are equally effective for all headache pain conditions. For instance, evidence of physical therapy in migraine is more controversial than in TTH, since migraine pathogenesis involves activation of sub-cortical structures and the trigemino-vascular system, whereas pathogenesis of TTH is more associated with musculoskeletal disorders, e.g. muscle pain. It seems that multimodal approaches including different interventions are more effective for patients with TTH, migraine and CeH.

Upcoming biological therapies in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune condition with unpredictable course, intermingled with flares and periods of remission. Although the prognosis of the disease has improved in the past decades, current therapies are still associated with treatment-related complications. Recently, there has been major progress in the understanding of the pathogenesis of SLE, paving the way for the development of new biological agents, potentially revolutionizing the treatment of SLE. This review summarizes available data on novel biological therapies for SLE, focusing on recent results from clinical trials. As a result of treatment strategies based upon an individualized therapeutic approach, it is hoped that the clinical view of SLE will change from a severe autoimmune disease to a condition in which significant damage, mortality and treatment related complications can be prevented in the majority of SLE patients.

SER consensus statement on the use of biologic therapy for systemic lupus erythematosus.

OBJECTIVE: To provide a reference to rheumatologists and other physicians involved in the treatment of systemic lupus erythematosus (SLE) who are using, or about to use biologic therapies. METHODS: Recommendations were developed following a nominal group methodology and based on systematic reviews. The level of evidence and degree of recommendation were classified according to a model proposed by the Center for Evidence Based Medicine at Oxford. The level of agreement was established through a Delphi technique. RESULTS: We have produced recommendations on the use of belimumab, the only biological agent with approved indications for SLE, and other biological agents without an indication for SLE. The objective of treatment is to achieve a complete clinical response, taken as the absence of perceived or evident disease activity. Nuances regarding the use of biologic therapies in SLE were reviewed as well, such as the evaluation that should be performed prior to administration and the follow up of patients undergoing these therapies. CONCLUSIONS: We present the SER recommendations for the use of biological therapies in patients with SLE.

Increase in body temperature during migraine attacks.

INTRODUCTION: Intermittent fever has been occasionally related to migraine, either as a migraine equivalent or as a migraine accompaniment. We present a case of recurrent increase in body temperature consistently associated with migraine headaches. METHODS: A 15-year-old girl reported a 3-year lasting history of migraine without aura, with a feeling of warmth occurring in each episode. Ancillary tests did not show any evidence of secondary headaches or any systemic disease. A 2-month headache diary was obtained, with daily records of headache intensity (0, no headache; 1, mild pain; 2, moderate pain; 3, severe pain) and simultaneous measurements of axillary temperature. Both parameters were registered in the evening, at 6:00 pm every day. The distribution of headache intensity and body temperature as well as the relationship between both variables over time were analyzed with nonparametric tests. RESULTS: The number of days without pain was 28 (45.2%); a mild headache was present on 13 days (21%), a moderate headache on 15 days (24.2%), and a severe headache on 6 days (9.7%). Headache days were associated with higher body temperature than headache-free days (median values: 37.3°C vs 36.6°C; Mann-Whitney U-test, P < 0.001). Moreover, a positive correlation was found between headache intensity and body temperature (Spearman's rho coefficient: 0.83, P < 0.001). CONCLUSIONS: Recurrent increase in body temperature may be another manifestation of the complex clinical spectrum of migraine. This symptom is probably related to hypothalamic involvement.

Mitochondrial dysfunction in antiphospholipid syndrome: implications in the pathogenesis of the disease and effects of coenzyme Q(10) treatment.

The exact mechanisms underlying the role of oxidative stress in the pathogenesis and the prothrombotic or proinflammatory status of antiphospholipid syndrome (APS) remain unknown. Here, we investigate the role of oxidative stress and mitochondrial dysfunction in the proatherothrombotic status of APS patients induced by IgG-antiphospholipid antibodies and the beneficial effects of supplementing cells with coenzyme Q(10) (CoQ(10)). A significant increase in relevant prothrombotic and inflammatory parameters in 43 APS patients was found compared with 38 healthy donors. Increased peroxide production, nuclear abundance of Nrf2, antioxidant enzymatic activity, decreased intracellular glutathione, and altered mitochondrial membrane potential were found in monocytes and neutrophils from APS patients. Accelerated atherosclerosis in APS patients was found associated with their inflammatory or oxidative status. CoQ(10) preincubation of healthy monocytes before IgG-antiphospholipid antibody treatment decreased oxidative stress, the percentage of cells with altered mitochondrial membrane potential, and the induced expression of tissue factor, VEGF, and Flt1. In addition, CoQ(10) significantly improved the ultrastructural preservation of mitochondria and prevented IgG-APS-induced fission mediated by Drp-1 and Fis-1 proteins. In conclusion, the oxidative perturbation in APS patient leukocytes, which is directly related to an inflammatory and pro-atherothrombotic status, relies on alterations in mitochondrial dynamics and metabolism that may be prevented, reverted, or both by treatment with CoQ(10).

Un caso de demencia frontotemporal en su variante lingüística fluente / A case of frontotemporal dementia in fluent linguistic variant

La dificultad para encontrar las palabras en una conversación y expresar lo que se piensa, así como la pérdida del conocimiento en la escritura de las palabras y su significado en presencia de un habla fluida; se evidencia en este estudio de caso; en una mujer de 62 años, con estudios en comercio y secretariado bilingüe, quien previamente a sus dificultades, se desempeñó como secretaria de alta gerencia con sobresalientes habilidades lingüísticas y en su escritura tipo palmer. Ha presentado una progresión gradual de sus déficits, evolucionando hacia un perfil de deterioro global cognoscitivo, específicamente de sus habilidades del lenguaje, déficit de memoria explicita verbal y semántica, alteración en el cálculo, disortografía, agrafia y disfunción ejecutiva, con parcial limitación para desempeñarse funcionalmente en las actividades de la vida diaria. Con la presentación de este caso, se encuentra un cuadro clínico inicial de afectación del sistema semántico y de la representación mental de las palabras, siendo congruente con una demencia semántica. Se presenta el papel fundamental de la evaluación neuropsicológica y la elaboración de la historia clínica, para efectuar un diagnóstico clínico diferencial entre las demencias degenerativas primarias como la enfermedad de Alzheimer y las variantes de las demencias frontotemporales.

The difficulty of finding words in a conversation and express what we think, and unconsciousness in the writing of words and their meaning in the presence of fluent speech, is evident in this study case, a woman of 62 years, with studies in business and bilingual secretary, who prior to his difficulties, she served as secretary of senior management with outstanding language skills and writing Palm OS. He has presented a gradual progression of their deficits, evolving towards a profile of global cognitive impairment, specifically their language skills, verbal explicit memory deficit and semantic change in the calculation, dysorthography, agraphia and executive dysfunction, with partial limitation to perform functionally in activities of daily living. By presenting this case, is a clinical initial involvement of the semantic system and the mental representation of words, being consistent with a semantic dementia. We report the role of neuropsychological assessment and the development of clinical history, to conduct a clinical differential diagnosis between primary degenerative dementia's such as Alzheimer's disease and variants of frontotemporal dementia.

Three new alkaloids from Galanthus nivalis and Galanthus elwesii.

Phytochemical studies on Galanthus species resulted in the isolation of three new compounds: 3,3'-O-(3',3''-dihydroxybutanoyl)hamayne and 11,3'-O-(3',3''-dihydroxybutanoyl)hamayne from G. nivalis and 2-O-(3'-hydroxybutanoyl)lycorine from G. elwesii. Additionally, 3,11-O-(3',3''-dihydroxybutanoyl)hamayne, 3,11,3'-O-(3',3'',3'''-trihydroxybutanoyl)hamayne, 8-O-demethylvasconine, tazettine, epimacronine, and ismine from G. nivalis; 2-O-(3'-acetoxybutanoyl)lycorine and incartine from G. elwesii; and hamayne, 11-O-(3'-hydroxybutanoyl)hamayne and lycorine from both species were isolated. Their structures were determined by EI-MS, HR-MS, CD, and 1D and 2D NMR (COSY, NOESY, HMQC, and HMBC) experiments.

Are manual therapies effective in reducing pain from tension-type headache?: a systematic review.

OBJECTIVES: A systematic review was performed to establish whether manual therapies have specific efficacy in reducing pain from tension-type headache (TTH). METHODS: Computerized literature searches were performed in MEDLINE, EMBASE, AMED, MANTIS, CINAHL, PEDro, and Cochrane databases. Papers were included if they described clinical (open noncontrolled studies) or randomized controlled trials in which any form of manual therapy was used for TTH, and if they were published after 1994 in the English language. The methodologic quality of the trials was assessed using the PEDro scale. Levels of scientific evidence, based on the quality and the outcomes of the studies, were established for each manual therapy: strong, moderate, limited, and inconclusive evidence. RESULTS: Only six studies met the inclusion criteria. These trials evaluated different manual therapy modalities: spinal manipulation (three trials), classic massage (one trial), connective tissue manipulation (two trials), soft tissue massage (one trial), Dr. Cyriax's vertebral mobilization (one trial), manual traction (one trial), and CV-4 craniosacral technique (one trial). Methodologic PEDro quality scores ranged from 2 to 8 points out of a theoretical maximum of 10 points (mean=5.8+/-2.1). Analysis of the quality and the outcomes of all trials did not provide rigorous evidence that manual therapies have a positive effect in reducing pain from TTH: spinal manipulative therapy showed inconclusive evidence of effectiveness (level 4), whereas soft tissue techniques showed limited evidence (level 3). CONCLUSIONS: The authors found no rigorous evidence that manual therapies have a positive effect in the evolution of TTH. The most urgent need for further research is to establish the efficacy beyond placebo of the different manual therapies currently applied in patients with TTH.

Spinal manipulative therapy in the management of cervicogenic headache.

Patients suffering from cervicogenic headache (CeH) are commonly treated with spinal manipulative therapy. We have analyzed the quality and the outcomes of published, randomized, controlled trials assessing the effectiveness of spinal manipulation in CeH. Among 121 relevant articles, only two met all the inclusion criteria. Methodological quality scores were 8/10 and 7/10 points. Only one of the trials made use of a headache diary. Both the trials reported positive (+) results on headache intensity, headache duration, and medication intake, so that spinal manipulative therapy obtained strong evidence of effectiveness (level 1) with regard to these outcomes. Conversely, spinal manipulation obtained no more than limited evidence (level 3) in reducing headache frequency, as it was analyzed only in one study with positive (+) results. A greater number of well-designed, randomized, controlled trials are required to confirm or refute the effectiveness of spinal manipulation in the management of CeH.

Mycophenolate mofetil in systemic lupus erythematosus: efficacy and tolerability in 86 patients.

OBJECTIVE: To assess the indications, efficacy, and tolerability of mycophenolate mofetil (MMF) in patients with systemic lupus erythematosus (SLE) resistant to other immunosuppressive therapy. METHODS: Records of 93 patients with SLE were retrospectively reviewed. Seven patients were excluded. The remaining 86 patients received other immunosuppressive drugs before MMF. Efficacy was measured by changes in daily oral prednisolone dose, European Consensus Lupus Activity Measurement Index (ECLAM), erythrocyte sedimentation rate (ESR), C-reactive protein, and dsDNA antibody titer. In renal patients, changes in serum creatinine, creatinine clearance, chromium-51 EDTA glomerular filtration rate (EDTA-GFR), and 24 hour urine protein excretion were also evaluated. RESULTS: Indications for MMF were mainly renal involvement (59% of patients), uncontrolled disease activity (14%), and other SLE related manifestations (13%). Overall, we found a significant reduction in the steroid dosage, ECLAM, ESR, and anti-dsDNA antibody titer. Renal patients (n = 35) showed a significant reduction in urinary 24 hour protein excretion. Levels of serum creatinine, creatinine clearance, and EDTA-GFR showed no significant change during treatment. Thirty-seven patients (42.8%) developed adverse events. Gastrointestinal intolerance in 25 (29%) and infections in 20 (23.2%) were the most frequent. The drug was discontinued in 14 (16.3%) patients due to side effects and 6 patients discontinued MMF because they achieved disease remission and were trying to conceive. MMF was stopped due to lack of efficacy in 12 patients. CONCLUSION: Our data suggest that MMF is a good therapeutic alternative for patients with SLE and renal involvement or refractory disease activity.

Manual therapies in the management of tension-type headache.

We describe a patient with successive attacks (40 to 90 minutes) of cluster-like headache associated with aphasia, and contralateral hemihypesthesia and hemiplegia. The condition can best be described as cluster-like headache aura status.