TIME, to move forward? Comment on “a universal outcome measure for headache treatments, care-delivery systems and economic analysis”

The paper from Steiner et al. suggests that an outcome measure expressed in time units may be an adequate method to assess the impact of headache disorders, regardless of diagnosis or health care setting, proving useful for cost-benefit analysis and health policy definition. Using time lost to each attack – weighted by disability – may prove to be a reliable measure to establish the effectiveness of acute treatment, but if considering also the attack frequency it could evaluate the effects of preventive strategies. A measure such as the Headache Gauge, which translates the proportion of time lost to headache -related disability, has proven to be applicable also in routine clinical practice as well, and can be tested in clinical trials and populational analysis. There are practical limitations, such as disability assessment and the need for prospective data collection to avoid recall bias but it seems consensual that impairment related to primary headache disorders is primarily driven by the TIME stolen from the perfect health status.info:eu-repo/semantics/publishedVersio

Cognitive functions during migraine attacks

Tese de doutoramento, Medicina (Neurologia), Universidade de Lisboa, Faculdade de Medicina, 2015Background: Attack-related cognitive symptoms in migraine are frequent yet scarcely characterized and undervalued as contributors of disability. Conflicting evidence arose about an increased risk of cognitive decline in older migraine patients. Objectives: (1) to study the occurrence of cognitive symptoms in migraine attacks; (2) to evaluate objective evidence of cognitive dysfunction in migraine attacks and its neuronal correlates and (3) to study the effect of persisting migraine in cognitive function or cognitive decline in older adults. Methods: Occurrence of attack-related cognitive symptoms was detailed by systematic literature review and a cross-sectional clinical-based systematic survey; their relevance to disability was studied prospectively using headache diaries. An instrument (Mig-SCog) was developed, validated and tested to identify and quantify attack-related subjective cognitive symptoms. Cognitive function during attacks was evaluated by a systematic literature review and a clinical-based prospective two-period randomized cross-over study using an extensive neuropsychological battery. A briefer battery was tested in repeated applications in interictal patients and controls. Brain perfusion during attacks was studied with arterial spin labeling magnetic resonance imaging (ASL-MRI) and cortical response to a working memory task with blood-oxygen level dependent functional magnetic resonance imaging (BOLD-fMRI). A prospective controlled cross-sectional population-based study of neuropsychological performance of older adults with persisting migraine and non-migraine headache was followed by a 5 years re-evaluation of the same sample, to screen for cognitive decline. Results: Cognitive symptoms were the most frequent non-migraine defining symptoms reported in the prodromic(37%) and headache(38%) phases of migraine attacks in a systematic review of 28 series, with a total sample of 8392 patients. Cognitive symptoms are also present in the postdromic or resolution phase, although fatigue (71%) is reported more often. Of 165 patients prospectively surveyed, 87% reported an average of 2.5 attack-related symptoms, over two-thirds executive (attention, processing efficiency and speed). Cognitive symptoms were ranked prospectively by 34 migraine patients recording 229 attacks, being second only to pain in terms of intensity and attack-related disability. An instrument to quantify migraine attack-related symptoms was constructed from a set of 43 candidate items, using factor analysis. The reduced 9 item Mig-SCog is fast to apply covering executive functions and language, having good internal consistency (Cronbachs’ alpha 0.82) and reliability (Cohen’s kappa 0.55) and high correlation with external validity measures such as the 43-candidate item list (rho=0.69) and the Cognitive Failures Questionnaires(rho=0.61). The Mig-SCog presents negligible recall bias (no difference in scores obtained during an attack or while headache free) and Migraine patients score it higher for migraine higher for migraine (7.9±4.6) than for non-headache pain (2.3±2.9, p<0.0006) or pain free (1.6±2.4, p<0.0006). Comparing Mig-SCog scores in migraine and tension-type headache patients, those were higher for migraine in all scale items (p<0.0001) except those related to naming (8 and 9). The AUC of Mig-SCog score for the diagnosis of Migraine was 0.835 (95% CI of 0.763-0.906, p< 0.0001) reinforcing specificity for migraine. Ten studies of neuropsychological evaluation during migraine attacks are available in the literature, only half had data allowing comparison of cognitive performance within and outside attacks (encompassing 163 migraine patients). All these were able to demonstrate some type of impairment (most often executive) although some bias could not be excluded from their study design. In our sample of 24 patients which completed an extensive neuropsychological evaluation in these two conditions (attack and headache-free) controlling for the majority of relevant bias (in particular the practice effect), performance was worse during the attack in the majority of cognitive tests, in particular in word reading speed (p=0.013), verbal learning (p=0.01), short term verbal recall with (p=0.01) and without (p=0.013) semantic cueing and delayed recall with (p=0.003) and without (p=0.05) semantic cues. Another sample of 24 interictal migraine patients and 24 matched controls performed equally in a shorter battery focused on executive functions that was applied twice with a short interval (average 45 days) to test the practice effect of repeated evaluations that was demonstrated in all tests, being significant in Stroop Interference test (p=0.002, multiplicity corrected); a meaningful score change was determined for each raw test scores. We were unable to find any relevant brain perfusion nor brain activation differences evoked by a working memory task during a spontaneous migraine without aura attack of an average intensity of 6.8 on a 0-10 VAS scale and an average duration of 16 hours in a sample of 13 women, compared to being headache-free. Persistent migraine or headache after the age of 50 related to worse performance in some neuropsychological tests (attention and processing speed in migraine patients, n=61; sematic memory and memory retrieval in non-migraine headache, n=50) in a population sample of 478 individuals tested extensively. After 5 years, 275 (57.5%) of the same sample were screened for cognitive decline, that occurred in 14.9% of the sample. Neither migraine nor non-migraine headache influenced the odds of decline. Discussion: Attack-related cognitive symptoms are very frequent, mostly executive and contribute to disability, supporting that they should be addressed as endpoint in clinical trials of acute migraine treatments and included in disability assessments. An efficient way to assess attack-related subjective cognitive symptoms in clinical practice or research is now available – the Mig-SCog. Although migraine-related reversible cognitive dysfunction was demonstrated during attacks, no advances on potential brain mechanisms underlying these findings were made. Interest is focused to obtain more functional data, with studies of evoked activation paradigms, functional connectivity and combined imaging and neurophysiological studies. Although persisting headache in older adults seems to influence executive performance, these changes are most likely adaptive and do not seem to influence the process of brain degeneration and associated cognitive decline

Cranial autonomic symptoms and neck pain in differential diagnosis of migraine

Cranial autonomic symptoms and neck pain have been reported to be highly prevalent in migraine, although they are rarely considered in clinical evaluation. The aim of this review is to focus on the prevalence, pathophysiology, and clinical characteristics of these two symptoms, and their importance in the differential diagnosis between migraines and other headaches. The most common cranial autonomic symptoms are aural fullness, lacrimation, facial/forehead sweating, and conjunctival injection. Migraineurs experiencing cranial autonomic symptoms are more likely to have more severe, frequent, and longer attacks, as well as higher rates of photophobia, phonophobia, osmophobia, and allodynia. Cranial autonomic symptoms occur due to the activation of the trigeminal autonomic reflex, and the differential diagnosis with cluster headaches can be challenging. Neck pain can be part of the migraine prodromal symptoms or act as a trigger for a migraine attack. The prevalence of neck pain correlates with headache frequency and is associated with treatment resistance and greater disability. The convergence between upper cervical and trigeminal nociception via the trigeminal nucleus caudalis is the likely mechanism for neck pain in migraine. The recognition of cranial autonomic symptoms and neck pain as potential migraine features is important because they often contribute to the misdiagnosis of cervicogenic problems, tension-type headache, cluster headache, and rhinosinusitis in migraine patients, delaying appropriate attack and disease management.info:eu-repo/semantics/publishedVersio

Cefaleia em salvas: Fisiopatogenia, clínica e tratamento

A Cefaleia em Salvas é, dentro das cefaleias primárias, a que apresenta a constelação clínica mais característica, tornando o diagnóstico bastante acessível. No entanto, dada a sua raridade, esta entidade é frequentemente ignorada pelos clínicos no diagnóstico diferencial das cefaleias. A importância do diagnóstico correcto é fundamental, pois esta violenta cefaleia tem uma abordagem terapêutica particular e, geralmente, bastante eficaz. Nesta breve revisão pretende-se fazer um enquadramento etiológico e fisiopatogénico desta patologia, descrever as suas características clínicas, com base nos critérios de diagnóstico existentes e relacionando-os com a realidade das séries descritas, abordar alguns aspectos relevantes do diagnóstico diferencial e propor os princípios de abordagem terapêutica mais consensuais e eficazes

Headache Health Services in Portugal – 2022: a survey by the Portuguese Headache Society

Introdução: Com o objectivo de otimizar os cuidados médicos prestados aos doentes com cefaleias em Portugal, a Sociedade Portuguesa de Cefaleias (SPC) transpôs para a realidade portuguesa as recomendações europeias para organização dos serviços de saúde neste contexto. Nesse documento são calculadas as necessidades de recursos, em termos de serviços de saúde, para garantir um apoio efetivo e de qualidade a estes doentes quer a nível de cuidados de saúde primários, quer de cuidados diferenciados, estes atribuídos à especialidade de neurologia. Neste sentido, considerou-se necessário efetuar um levantamento relativo à oferta de serviços de saúde diferenciados em cefaleias existente em Portugal e à sua perspetiva de evolução, nos próximos anos, de forma a perceber se corresponde às necessidades estimadas. Métodos: Foi disponibilizado um inquérito online aos sócios da SPC e da Sociedade Portuguesa de Neurologia que caracteriza a oferta de serviços de saúde diferenciados em cefaleias. Resultados: Foram obtidas respostas de 52 médicos, pertencentes a 40 instituições, 24(59%) do sistema nacional de saúde, cobrindo adequadamente o território nacional exceto nas regiões do Alentejo e Algarve. A maioria dos centros tem consulta de cefaleias, 88% com médicos dedicados e 91% dispondo de técnicas avançadas de tratamento (bloqueios, toxina e anticorpos monoclonais). Na maioria destes centros há 1 ou 2 médicos atribuídos a esta função, oferecendo em média 169 consultas por dia útil – cada instituição oferece, em média, 20 consultas por semana. O tempo de espera para a consulta é superior a 3 meses em 65% dos centros do SNS, mas as consultas e tratamentos tem a duração e dispõem de recursos técnicos adequados. A maioria dos centros tem expectativa de aumentar a oferta nos próximos 2 anos. Conclusão: Muito embora com limitações condicionadas pelo método, podemos afirmar que existem um número de centros adequado para apoio diferenciado aos doentes com cefaleias em Portugal, no entanto com uma oferta inferior à necessária (cerca de 13%), condicionada sobretudo por escassez de tempo médico atribuído a esta função.Introduction: Aiming to improve the medical care provided to patients with headaches in Portugal, the Portuguese Headache Society (SPC) transposed the Eu-ropean recommendations for the organization of health services for headache to the Portuguese context. This document calculates the need for resources, in terms of health services, to ensure effective and quality support for headache patients, both in terms of primary and specialized care, the latter being attributed to neurology. In this sense, it was considered necessary to survey he offer of differentiated health services for headaches in Portugal and its’ perspective of evolution, in the coming years, in order to understand if it corresponds to the estimated needs. Methods: An online survey was made available to members of the SPC and the Portuguese Society of Neurology, which characterizes the provision of differentiated health services in headache. Results: Responses were obtained from 52 doctors, of 40 health care facilities, 24 (59%) belonging to the national health system. The national territory was covered adequately, except in the regions of Alentejo and Algarve. Most centers have headache clinics, 88% with dedicated doctors and 91% with advanced treatment tech-niques (nerve blocks, botulinum toxin and monoclonal antibodies). Most of these centers have only 1 or 2 physicians assigned to this function, providing an average of 169 consultations per working day – each institution offers an average of 20 consultations per week. The waiting time for the consultation is over 3 months in 65% of the centers of the SNS, but the consultations and treatments allocated time is adequate and most have adequate technical resources. Most centers expect to in-crease their offer in the next 2 years. Conclusion: Although with limitations conditioned by the method, we can state that there are an adequate number of centers for differentiated support of headaches patients in Portugal, although the services offer in lower than necessary (about 13%), conditioned mainly by scarcity of medical time assigned to this role.info:eu-repo/semantics/publishedVersio

Vaccination Controversies: An Adult Case of Post-Vaccinal Acute Disseminated Encephalomyelitis

Acute disseminated encephalomyelitis is a rare inflammatory demyelinating multifocal disease of the central nervous system that typically occurs in children following vaccination or exanthematous viral infections and conveys an elevated risk of neurological sequelae unless promptly recognized and treated. We describe an adult case of acute disseminated encephalomyelitis following vaccination against Mumps, Measles and Rubella, presenting with fever and progressive neurological deficits which improved under systemic corticosteroid therapy. Considering the ongoing public debate regarding universal vaccination and the surge of previously controlled infectious diseases, we aim not only to underline the need for a rigorous assessment of vaccination safety on adult patients in order to prevent misguidance of public opinion, but also to alert clinicians for an early diagnosis of acute disseminated encephalomyelitis in these patients, the incidence of which we speculate may be rising

Relevant factors for neurologists to define effectiveness of migraine preventive drugs and take decisions on treatment: my-LIFE European Delphi survey

Mètode Delphi; Eficàcia dels fàrmacs preventius de la migranyaDelphi survey; Effectiveness of migraine preventive drugsMétodo Delfos; Eficacia de los medicamentos preventivos contra la migrañaBackground Clinical guidelines agree that preventive treatment should be considered in patients with uncontrolled migraine despite acute medications or patients with ≥4 migraine days per month. However, the criteria to define the effectiveness of treatment and the factors that inform the decision to (dis)continue it are not clearly defined in clinical practice. Methods Overall, 148 healthcare practitioners from five European countries completed a two-wave questionnaire. The Steering Committee defined a simulated set of 108 migraine patient profiles based on the combination of five factors (frequency of the attacks, intensity of the attacks, use of acute migraine medications, patient perception and presence/absence of tolerable side effects). These profiles were used in a Delphi survey among European neurologists to identify the criteria that should be used to decide treatment response and continuation using a conjoint analysis approach. Results Consensus was reached for 82/108 (76%) of profiles regarding treatment response, and for 86/108 (80%) regarding treatment continuation. Multivariable logistic regression analysis showed that a ≥50% reduction in the use of acute migraine medications and positive patient's perception of treatment were the most important factors that lead to the decision of continuing (combined factors, OR = 18.3, 95% CI 13.4–25.05). Conclusions This survey identifies two relevant outcome measures: one objective (use of acute migraine treatment medications) and one subjective (positive patient perception) that guide the clinician decision to continue preventive treatment in migraine patients. Significance In clinical practice, criteria to define the effectiveness of migraine preventive treatment and factors that guide treatment stop or continuation are not clearly defined. In this simulated clinical setting study, a reduction in the use of acute migraine medications was the factor associated with preventive treatment effectiveness definition. This study also revealed that factors strongly associated with the decision of treatment continuation in real life are the acute migraine medications use and a positive patient's perception of treatment effectiveness.Novartis Pharma AG financially supported the development of this project, the medical writing assistance and the page processing charges for this article. The authors have received no payment to write this article

Working memory during spontaneous migraine attacks: an fMRI study

Objective: To investigate the neural correlates of working memory during a spontaneous migraine attack compared to the interictal phase, using functional magnetic resonance imaging (fMRI). Background: Cognitive disturbances are commonly observed during migraine attacks, particularly in the headache phase. However, the neural basis of these changes remains unknown. Methods: In a fMRI within-subject test-retest design study, eleven women (32 years of age, average) with episodic migraine were evaluated twice, first during a spontaneous migraine attack, and again in a pain-free period. Each session consisted in a cognitive assessment and fMRI while performing a working memory task (N-back). Results: Cognitive test scores were lower during the ictal session than in the pain-free session. Regions typically associated with working memory were activated during the N-back task in both sessions. A voxel wise between session comparison showed significantly greater activation in the left frontal pole and orbitofrontal cortex during the attack relative to the interictal phase. Conclusion: Migraine patients exhibited greater activation of the left frontal pole and orbitofrontal cortex while executing a verbal working memory task during a spontaneous migraine attack when compared to the interictal state. Given the association of these regions with pain processing and inhibitory control, these findings suggest that patients recruit inhibitory areas to accomplish the cognitive task during migraine attacks, a neural signature of their cognitive difficulties.info:eu-repo/semantics/publishedVersio

Cognitive performance along the migraine cycle: a negative exploratory study

Migraine patients frequently report cognitive difficulties in the proximity and during migraine attacks. We performed an exploratory comparison of executive functioning across the four stages of the migraine cycle. Consecutive patients with episodic migraine undertook cognitive tests for attention, processing speed, set-shifting, and inhibitory control. Performance was compared between patients in different migraine stages, controlling for attack frequency and prophylactic medication. One hundred forty-three patients (142 women, average age 36.2 ± 9.9 years) were included, 28 preictal (≤48 h before the attack), 21 ictal (during the attack), 18 postictal (≤24 h after attack), and 76 interictal. Test performance (age and literacy adjusted z-scores) was not significantly different across migraine phases, despite a tendency for a decline before the attack. This negative study shows that cognitive performance fluctuates as patients approach the attack. To control for individual variability, this comparison needs to be better characterized longitudinally with a within-patient design.info:eu-repo/semantics/publishedVersio

Cognitive aging in migraine sufferers is associated with more subjective complaints but similar age-related decline: a 5-year longitudinal study

Objectives and background: The effect of headache on cognitive performance is controversial, due to conflicting results obtained from studies in clinical or population settings. We aimed to understand if migraine and other headaches modify the rates of decline on different cognitive measures, during a 5-year interval. Design and method: A cohort of community dwelling adults (> 50 years) with migraine (MH), non-migraine headaches (NMH) and controls without headache (WoH), was assessed by a comprehensive neuropsychological battery with tests of memory, language and executive functions, repeated 5 years apart. Change in performance between baseline and reevaluation was compared between groups, and controlled for age, gender, literacy and depressive symptoms. Results: A total of 275 participants (78.5% WoH, 12.7% MH, 8.7% NMH) were reevaluated (average age 70.40 + 8.34 years, 64% females). Cognitive decline or dementia occurred in 11.4%, with a similar proportion among the three groups. Although MH participants had significantly more subjective cognitive complaints (p = 0.030, 95%CI:]-3.929,-0.014[), both MH and NMH subjects showed an age-associated decline identical to controls. Furthermore, migraine features (disease and attack duration, frequency and aura) were unrelated with cognitive performance. Conclusion: Migraine and non-migraine headache are not associated with increasing risk of dementia or cognitive decline at an older age although subjects with migraine have more cognitive complaints. Longer longitudinal studies are necessary to understand if this pattern persists for more than 5 years.info:eu-repo/semantics/publishedVersio