Migraine-specific quality of life questionnaire and relapse on medication overuse headache

Background: The management of Medication overuse headache (MOH) represents a difficult challenge for clinicians and headache experts, particularly for the responder rate after a successful withdrawal treatment. The purpose of this study was to investigate the role of demographic and clinical characteristics as well as the score of Migraine-Specific Quality of Life Questionnaire (MSQ), Migraine Disability Questionnaire and Leeds Dependence Questionnaire in predicting a response after a successful withdrawal treatment in patients with MOH. Methods: This ancillary study is part of a randomized trial that demonstrated the safety and the efficacy of a 3-month treatment with sodium valproate (VPA) (800 mg/day vs placebo) in MOH. Demographic and clinical characteristics and questionnaire results were obtained from the entire sample. Results: A significant correlation was found only between MOH relapse and the total MSQ score, the Role Preventive sub-scale and the Emotional Function sub-scale, suggesting a poorer quality of life in non responders. Conclusion: A high MSQ score could be associated with a poor short-term outcome in MOH patients after a successful treatment with detoxification followed by a new treatment

Visual stimulation and frequency of focal neurological symptoms engage distinctive neurocognitive resources in migraine with aura patients. A study of resting-state functional networks

Introduction: Several functional neuroimaging studies on healthy controls and patients with migraine with aura have shown that the activation of functional networks during visual stimulation is not restricted to the striate system, but also includes several extrastriate networks. Methods: Before and after 4 min of visual stimulation with a checkerboard pattern, we collected functional MRI in 21 migraine with aura (MwA) patients and 18 healthy subjects (HS). For each recording session, we identified independent resting-state networks in each group and correlated network connection strength changes with clinical disease features. Results: Before visual stimulation, we found reduced connectivity between the default mode network and the left dorsal attention system (DAS) in MwA patients compared to HS. In HS, visual stimulation increases functional connectivity between the independent components of the bilateral DAS and the executive control network (ECN). In MwA, visual stimulation significantly improved functional connectivity between the independent component pairs salience network and DAS, and between DAS and ECN. The ECN Z-scores after visual stimulation were negatively related to the monthly frequency of aura. Conclusions: In individuals with MwA, 4 min of visual stimulation had stronger cognitive impact than in healthy people. A higher frequency of aura may lead to a diminished ability to obtain cognitive resources to cope with transitory but important events like aura-related focal neurological symptoms

Migraine with aura in the locker room: three case reports

It is well known that physical activity can aggravate the intensity of the headache, but the pathophysiological relationship between exertion and aura is still unknown. Anecdotal reports describe episodes of migraine preceded by head trauma and visual symptoms, migraine prodrome symptoms after unusually strenuous running with no subsequent head pain or recurrent attacks of hemiplegic migraine induced only by exertion. We describe the cases of three young men with recurrent episodes of migraine with aura occurring in the locker room shortly after a football match. Since the symptoms could mimic important pathologies in approximately 10% of these of headaches, it was mandatory to exclude a secondary form of headache in these patients. Several theories exist regarding the cause of primary exertional headache, but the pathogenesis of migraine triggered by physical activity has still not been identified. The present International Classification of Headache Disorders does not mention sport/exercise-induced migraine with aura episodes as primary headache. Since there are many cases described in the literature of migraine with aura triggered only by exercise, it may be helpful to specify, in the typical aura with migraine headache comments, that in some cases it can be exclusively triggered by sport/exercise

A transgenic mouse model for uromodulin-associated kidney diseases shows specific tubulo-interstitial damage, urinary concentrating defect and renal failure

Uromodulin-associated kidney diseases (UAKD) are autosomal-dominant disorders characterized by alteration of urinary concentrating ability, tubulo-interstitial fibrosis, hyperuricaemia and renal cysts at the cortico-medullary junction. UAKD are caused by mutations in UMOD, the gene encoding uromodulin. Although uromodulin is the most abundant protein secreted in urine, its physiological role remains elusive. Several in vitro studies demonstrated that mutations in uromodulin lead to endoplasmic reticulum (ER) retention of mutant protein, but their relevance in vivo has not been studied. We here report on the generation and characterization of the first transgenic mouse model for UAKD. Transgenic mice that express the C147W mutant uromodulin (Tg(UmodC147W)), corresponding to the well-established patient mutation C148W, were compared with expression-matched transgenic mice expressing the wild-type protein (Tg(Umodwt)). Tg(UmodC147W) mice recapitulate most of the UAKD features, with urinary concentrating defect of renal origin and progressive renal injury, i.e. tubulo-interstitial fibrosis with inflammatory cell infiltration, tubule dilation and specific damage of the thick ascending limb of Henle's loop, leading to mild renal failure. As observed in patients, Tg(UmodC147W) mice show a marked reduction of urinary uromodulin excretion. Mutant uromodulin trafficking to the plasma membrane is indeed impaired as it is retained in the ER of expressing cells leading to ER hyperplasia. The Tg(UmodC147W) mice represent a unique model that recapitulates most of the features associated with UAKD. Our data clearly demonstrate a gain-of-toxic function of uromodulin mutations providing insights into the pathogenetic mechanism of the disease. These findings may also be relevant for other tubulo-interstitial or ER-storage disorders

P066. Migraine with aura in the locker room: 4 case reports

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Stopping Onabotulinum Treatment after the First Two Cycles Might Not Be Justified: Results of a Real-life Monocentric Prospective Study in Chronic Migraine

IntroductionOnabotulinum toxin A (OnabotA) cyclic treatment is approved for the prophylactic treatment of chronic migraine (CM), a highly disabling disorder. Although treatment response varies among patients, current guidelines suggest to stop treatment after cycle 2 if no response is achieved. This prospective study aimed to define, in real-life setting, the evolution of the response to OnabotA over five cycles of treatment among patients non-responding to cycle 1. The results of this study might help in decision-making, in particular whether prosecuting OnabotA further or not, when facing a patient not responding to cycle 1.MethodsPatients failing to respond at cycle 1 were recruited to complete five cycles. Key outcomes were: (i) a ≥50% reduction in headache days, (ii) a ≥50% reduction in total cumulative hours of headache on headache days and (iii) a ≥5-point improvement in Headache Impact Test-6 (HIT-6) scores.ResultsOverall, 56 patients were included. Mean age was 45.7 years (female 83.9%). Severe (≥60) HIT-6 score was reported at baseline by 95.8% of patients. Responders (headache days reduction of more than 50%) progressively increased cycle after cycle, doubling from cycle 2 to cycle 5 (from 27 to 48%). In addition, patients regressed from CM to episodic migraine moving on with each cycle, with 78% of them reaching less than nine migraine days/month after cycle 5. The headache days per month decreased significantly from cycle 1 to cycle 5 (overall from 23.3 ± 5.7 to 9.2 ± 3.6; p < 0.001). During 12 months (5 cycles), migraine days per month progressively abated (from 18.5 to 8.7; p < 0.001), days with symptomatic medications intake/month consistently decreased (from 17.4 to 8.1; p < 0.001), and mean HIT-6 score lowered (from 72.4 ± 5.7 to 50.2 ± 4.3; p < 0.001).ConclusionThe positive effect of OnabotA treatment spreads over the course of the treatment and might also manifest late in treatment course among patients with no benefit after the first two cycles. Thus, the results of this real-life study suggest to extend OnabotA treatment further, beyond cycle 2, to avoid premature withdrawal in patients who would have become responders at cycle 3, 4, or 5

Immunological findings in patients with migraine and other primary headaches: a narrative review

Experimental findings suggest an involvement of neuroinflammatory mechanisms in the pathophysiology of migraine. Specifically, preclinical models of migraine have emphasized the role of neuroinflammation following the activation of the trigeminal pathway at several peripheral and central sites including dural vessels, the trigeminal ganglion, and the trigeminal nucleus caudalis. The evidence of an induction of inflammatory events in migraine pathophysiological mechanisms has prompted researchers to investigate the human leukocyte antigen (HLA) phenotypes as well as cytokine genetic polymorphisms in order to verify their potential relationship with migraine risk and severity. Furthermore, the role of neuroinflammation in migraine seems to be supported by evidence of an increase in pro-inflammatory cytokines, both ictally and interictally, together with the prevalence of Th1 lymphocytes and a reduction in regulatory lymphocyte subsets in peripheral blood of migraineurs. Cytokine profiles of cluster headache (CH) patients and those of tension-type headache patients further suggest an immunological dysregulation in the pathophysiology of these primary headaches, although evidence is weaker than for migraine. The present review summarizes available findings to date from genetic and biomarker studies that have explored the role of inflammation in primary headaches.Experimental evidence from animal models of trigemino-vascular activation suggests a pivotal role for neurogenic inflammation in migraine. The prevalent involvement of pro-inflammatory mediators and specifically cytokines in migraine is strongly supported by data on peripheral blood levels from migraine patients assessed both ictally and interictally. A role of neuroinflammation seems to be plausible also for the pathogenesis of cluster headache, and a lesser extent, of tension-type headache, but, in order to definitely clarify this issue, further studies should be performed in the next years

iIteratrial shunting through an asymptomatic patent foramen ovale in thoracic surgery

Background: Patent foramen ovale (PFO) is present in as many as 25% of the general population and is considered an irrelevant condition in healthy subjects. Here, we sought to determine an association between an asymptomatic PFO at baseline and postoperative short-term adverse events in patients undergoing major pulmonary resection for lung cancer. In addition, we evaluated for the rate of PFO after pulmonary resections. Methods: This prospective, observational study assessed patients by transcranial Doppler with contrast at baseline and discharge. To confirm interatrial shunting, patients with positive transcranial Doppler at baseline also underwent contrast transthoracic echocardiography. Multivariate logistic regression models were adopted to investigate for independent factors that could have been associated with complications. Backward stepwise procedure was used for model selection. Results: Median age was 67.7 ± 9.2 years (range, 36 to 86), and 67% were men. Overall, 18 patients underwent pneumonectomy, 11 bilobectomy, and 118 lobectomy; 54% underwent right-sided procedure and 46%, left-sided. One perioperative death was recorded, and 34 patients had one or more cardiopulmonary complications. At baseline, PFO was positive in 25% (37 of 147) and negative in 75% (110 of 147); of the latter, 11% were positive at discharge. Detection of PFO at baseline, on multivariate analysis, was significantly associated with a risk of postoperative complications (odds ratio 2.5; 95% confidence interval: 1.1 to 5.8). Specifically, we observed a significant association between atrial fibrillation and positive PFO at baseline (odds ratio 3.5; 95% confidence interval: 1.4 to 9.0). Conclusions: Preoperative asymptomatic PFO was independently associated with postoperative adverse events. Moreover, 11% of patients who had negative transcranial Doppler studies at baseline had asymptomatic PFOs at discharge. Larger prospective studies are needed to further investigate for a prognostic impact of PFO in thoracic surgery