Revolutionizing migraine management: advances and challenges in CGRP-targeted therapies and their clinical implications.

Migraine, a prevalent neurological disorder, affects approximately 14.1% of the global population and disproportionately impacts females. This debilitating condition significantly compromises quality of life, productivity, and incurs high healthcare costs, presenting a challenge not only to individuals but to societal structures as a whole. Despite advances in our understanding of migraine pathophysiology, treatment options remain limited, necessitating ongoing research into effective therapies. This review delves into the complexity of migraine management, examining the roles of genetic predisposition, environmental influences, personalized treatment approaches, comorbidities, efficacy and safety of existing acute and preventive treatments. It further explores the continuum between migraine and tension-type headaches and discusses the intricacies of treating various migraine subtypes, including those with and without aura. We emphasize the recent paradigm shift toward trigeminovascular activation and the release of vasoactive substances, such as calcitonin gene-related peptide (CGRP), which offer novel therapeutic targets. We assess groundbreaking clinical trials, pharmacokinetic and pharmacodynamic perspectives, safety, tolerability, and the real-world application of CGRP monoclonal antibodies and gepants. In the face of persisting treatment barriers such as misdiagnosis, medication overuse headaches, and limited access to specialist care, we discuss innovative CGRP-targeted strategies, the high cost and scarcity of long-term efficacy data, and suggest comprehensive solutions tailored to Turkiye and developing countries. The review offers strategic recommendations including the formulation of primary care guidelines, establishment of specialized outpatient clinics, updating physicians on novel treatments, enhancing global accessibility to advanced therapies, and fostering patient education. Emphasizing the importance of lifestyle modifications and holistic approaches, the review underscores the potential of mass media and patient groups in disseminating critical health information and shaping the future of migraine management.

Chiral electrocatalysts eclipse water splitting metrics through spin control.

Continual progress in technologies that rely on water splitting are often hampered by the slow kinetics associated with the oxygen evolution reaction (OER). Here, we show that the efficiency of top-performing catalysts can be improved, beyond typical thermodynamic considerations, through control over reaction intermediate spin alignment during electrolysis. Spin alignment is achieved using the chiral induced spin selectivity (CISS) effect and the improvement in OER manifests as an increase in Faradaic efficiency, decrease in reaction overpotential, and change in the rate determining step for chiral nanocatalysts over compositionally analogous achiral nanocatalysts. These studies illustrate that a defined spatial orientation of the nanocatalysts is not necessary to exhibit spin selectivity and therefore represent a viable platform for employing the transformative role of chirality in other reaction pathways and processes.

Effects of elevated temperature, reduced hydroperiod, and invasive bullfrog larvae on pacific chorus frog larvae.

Climate change and invasive species threaten many ecosystems, including surface freshwater systems. Increasing temperatures and reduced hydroperiod due to climate change may promote the persistence of invasive species and facilitate new invasions due to potentially higher tolerance to environmental stress in successful invaders. Amphibians demonstrate high levels of plasticity in life history characteristics, particularly those species which inhabit both ephemeral and permanent water bodies. We tested the influence of two projected effects of climate change (increased temperature and reduced hydroperiod) on Pacific chorus frog (Pseudacris regilla) tadpoles alone and in combination with the presence of tadpoles of a wide-spread invasive amphibian, the American bullfrog (Lithobates catesbeianus). Specifically, we explored the effects of projected climate change and invasion on survival, growth, mass at stage 42, and development rate of Pacific chorus frogs. Direct and indirect interactions between the invasive tadpole and the native tadpole were controlled via a cage treatment and were included to account for differences in presence of the bullfrog compared to competition for food resources and other direct effects. Overall, bullfrogs had larger negative effects on Pacific chorus frogs than climate conditions. Under future climate conditions, Pacific chorus frogs developed faster and emerged heavier. Pacific chorus frog tadpoles developing in the presence of American bullfrogs, regardless of cage treatment, emerged lighter. When future climate conditions and presence of invasive American bullfrog tadpoles were combined, tadpoles grew less. However, no interaction was detected between climate conditions and bullfrog presence for mass, suggesting that tadpoles allocated energy towards mass rather than length under the combined stress treatment. The maintenance of overall body condition (smaller but heavier metamorphs) when future climate conditions overlap with bullfrog presence suggests that Pacific chorus frogs may be partially compensating for the negative effects of bullfrogs via increased allocation of energy towards mass. Strong plasticity, as demonstrated by Pacific chorus frog larvae in our study, may allow species to match the demands of new environments, including under future climate change.

Aging and the perception of texture-defined form.

In this study 28 younger and older observers discriminated the global shapes of objects that were defined by differences in texture. The judged stimulus patterns were 3-point micropattern textures. On any given trial, a texture-defined shape (either a vertically- or horizontally-oriented rectangle) was presented; the observers' task was to discriminate between the two rectangles. The task difficulty was manipulated by varying the deviation from colinearity of each of the individual 3-point texture elements between figure and background (the larger the difference in deviation between figure and ground, the higher the discrimination performance). The results revealed a substantial effect of age. In order for the older observers to reliably discriminate the shape of the target rectangle (with a d' value of 1.5), they needed differences from colinearity that were 54.4 percent larger than those required for the younger observers. While older adults can utilize differences in texture to perceive global shape, their ability is nevertheless significantly impaired.

Temporal integration in the perception and discrimination of solid shape.

Two experiments evaluated the importance of temporal integration for the perception and discrimination of solid object shape. In Experiment 1, observers anorthoscopically viewed moving or stationary cast shadows of naturally shaped solid objects (bell peppers, Capsicum annuum) through narrow (4-mm wide) slits. At any given moment, observers could only see a very small portion of the overall object shape (generally less than 10%). The results showed that the observers' discrimination performance for the moving cast shadows was much higher than that obtained for the stationary shadows, demonstrating the ability to temporally integrate the piecemeal momentary information about shape that was available through the narrow apertures. In a second experiment, estimates of the strength of the observers' impressions of solid shapes rotating in depth were obtained as well as discrimination accuracies; perceptions of the original moving condition were compared with a new condition where the frames of the apparent motion sequences depicting solid objects in continuous motion (behind the slits) were randomly scrambled. The observers perceived the anorthoscopic displays as depicting solid objects rotating in depth, but only in the continuous motion condition. Interestingly, the discrimination performance in the scrambled condition remained relatively high-observers were still able to integrate information across the multiple scrambled frames in order to produce discrimination performance that was significantly higher than that obtained in the stationary shadow condition. This study was the first to thoroughly evaluate whether and to what extent human observers can effectively discriminate and perceive solid object shape anorthoscopically.

Identifying key features of effective active learning: the effects of writing and peer discussion.

We investigated some of the key features of effective active learning by comparing the outcomes of three different methods of implementing active-learning exercises in a majors introductory biology course. Students completed activities in one of three treatments: discussion, writing, and discussion + writing. Treatments were rotated weekly between three sections taught by three different instructors in a full factorial design. The data set was analyzed by generalized linear mixed-effect models with three independent variables: student aptitude, treatment, and instructor, and three dependent (assessment) variables: change in score on pre- and postactivity clicker questions, and coding scores on in-class writing and exam essays. All independent variables had significant effects on student performance for at least one of the dependent variables. Students with higher aptitude scored higher on all assessments. Student scores were higher on exam essay questions when the activity was implemented with a writing component compared with peer discussion only. There was a significant effect of instructor, with instructors showing different degrees of effectiveness with active-learning techniques. We suggest that individual writing should be implemented as part of active learning whenever possible and that instructors may need training and practice to become effective with active learning.

A comparative ID migraine screener study in ophthalmology, ENT and neurology out-patient clinics.

Migraine is more likely to be misdiagnosed in patients with comorbid diseases. Not only primary care physicians, but also specialists might misdiagnose it due to the lack of diagnostic criteria awareness. The ID migraine test is a reliable screening instrument that may facilitate and accelerate migraine recognition. This study aimed to compare the prevalence and characteristics of migraine in a large sample of patients admitted to clinics of ophthalmology (OC), ear, nose and throat diseases (ENTC) and neurology (NC), as well as to validate the use of the ID migraine test in OC and ENTC settings. This was a multicentre (11 cites) study of out-patients admitting either to NC, ENTC or OC of the study sites during five consecutive working days within 1 week. From each of the clinics, 100 patients were planned to be recruited. All recruited patients were interviewed and those having a headache complaint received an ID migraine test and were examined for headache diagnosis by a neurologist, blinded to the ID migraine test result. A total of 2625 subjects were recruited. Only 1.3% of OC patients and 5.4% of ENTC patients have been admitted with a primary complaint of headache, whereas the percentage of NC patients suffering from headache was 37.6%. Whereas 138 patients (19.3%) in OC, 154 (17.3%) in ENTC and 347 (34%) in NC were found to be ID migraine test positive, 149 patients (20.8%) in OC, 142 (16%) in ENTC and 338 (33.1%) in NC were diagnosed with migraine. The sensitivity, specificity, and positive and negative predictive ratios of the ID migraine test were found to be similar in all clinics. An important fraction of the patients admitted to NC, as well as to OC and ENTC, for headache and/or other complaints were found out to have migraine by means of a simple screening test. This study validated the ID migraine test as a sensitive and specific tool in OC and ENTC, encouraging its use as a screening instrument.

Can ID Migraine be used as a screening test for adolescent migraine?

Although the ID Migraine has been developed and used for adults, it can also be used in adolescents. We aimed to investigate the validity of the ID Migraine in the adolescent student population. The study was performed on 1064 adolescents aged 12-17 years. A face-to-face semistructured interview was conducted with students after they had answered a 17-item questionnaire on sociodemographics and headache. Students who had had two or more headache attacks during the last 3 months then answered the ID Migraine. The sensitivity and specificity of the ID Migraine were 62.1% and 71.1%, respectively. The sensitivity was higher for patients with migraine with aura (71.1%), for girls (71.3%) and for younger adolescents (69.1%). The specificity was higher for boys (77.9%) and for older adolescents (73.3%). The kappa value was 0.316 (P < 0.001). Although the kappa value of the ID Migraine is low, the test may be a useful tool in screening adolescent migraine after some changes are made.

Investigation of neuromuscular transmission in some rare types of migraine.

The aim of this study was to delineate any dysfunction of neuromuscular transmission (NMT) by single-fibre electromyography (SFEMG) in some rare types of migraine. Recent studies have shown subclinical dysfunction of NMT in migraine with aura and cluster headache by using SFEMG, whereas another recent study has shown NMT to be normal in familial hemiplegic migraine (FHM) with CACNA1A mutations. Thirty patients with rare primary headache syndromes [18 with sporadic hemiplegic migraine (SHM), six with FHM and six with basilar-type migraine (BM)] and 15 healthy control subjects without any headache complaints underwent nerve conduction studies, EMG and SFEMG during voluntary contraction of the extensor digitorum communis muscle. Ten to 20 different potential pairs were recorded and individual jitter values calculated. The results obtained from patient groups were compared with those from the normal subjects. Of 600 individual jitter values of the patients, 27 (4.5%) were abnormally high, whereas only 3/205 (1.5%) jitter values from normal subjects were abnormal. Abnormal NMT was found in 4/30 (13.3%) patients (three SHM and one BM), but in none of the control subjects. Only in SHM patients was the number of individual abnormal jitter values slightly but significantly different from normal controls. The present study demonstrates that subclinical NMT abnormality is slightly present in only SHM and BM patients, but not in FHM patients.

The impact of education on the diagnostic accuracy of tension-type headache and migraine: a prospective study.

General practitioners (GPs) diagnose and treat headache in primary care settings. The objective of this study was to investigate the effect of a 2-day headache education programme for GPs primarily on diagnostic accuracy. The education programme included theoretical lectures and face-to-face patient evaluation with headache specialists. Three GPs evaluated headache patients before and after the programme. Each GP was planned to interview a total of 60 patients (30 before, 30 after the programme). All patients were evaluated by headache specialists following evaluation by the GPs. A total of 189 patients were included in this study. Diagnostic accuracy increased from 56.3% to 81.0% after the headache education programme (P < 0.001), which also significantly improved the choice of proper treatment (P = 0.043). The headache education programme for GPs significantly improved diagnostic accuracy in patients with tension-type headache and the choice of proper treatment. Such education programmes can be standardized and given to GPs working in the primary care setting. These programmes can be arranged locally by the universities and might have a favourable impact on the diagnosis and treatment of headache.

Effects of oral isotretinoin therapy on peripheral nerve functions: a preliminary study.

Accumulating evidence over the past decade indicates that synthetic retinoids may be capable of affecting both growth and differentiation of nervous tissue. Our aim was to substantiate possible side-effects of oral isotretinoin therapy on peripheral nerve functions, both neurologically and neurophysiologically. We performed neurological examination and electroneuromyographic studies on 18 patients with various skin diseases before, at the third month, and at the end of isotretinoin treatment. Abnormal neurophysiological findings in this study point towards a typical distal, length-dependent and predominantly sensory polyneuropathy. Clinicians should be aware of possible neurological sensorial symptoms during isotretinoin therapy. In our opinion, electroneuromyographic investigation should be performed on all patients reporting symptoms (e.g. paresthesia, numbness, sensory loss) before and during oral isotretinoin treatment. The precise clinical significance of the isotretinoin-induced neurophysiological alterations reported here remains to be determined in further studies.

Comparison of pre-headache phases and trigger factors of migraine and episodic tension-type headache: do they share similar clinical pathophysiology?

Trigger factors, signs and symptoms of the preheadache phases of episodic tension-type headache (ETTH), typical aura with non-migraine headache (TANMH), migraine with (MA) and without aura (MwA) may show similar features. Our objective was to investigate the preheadache phases and trigger factors of these headache types. Questionnaires including trigger factors, signs and symptoms of preheadache phases were answered by all headache patients. A total of 96 patients, 31 ETTH, nine TANMH, 23 MA and 33 MwA patients were included in this study. Analysis of seven groups consisting of 18 individual trigger factors showed that only two groups and five individual trigger factors were significantly different between groups. Hunger and odour were significantly more common in MA, MwA and TANMH patients. Foods were a significant precipitant factor for headache in MA patients. Head and neck movements were important trigger factors in ETTH. In prodrome phase only one out of three groups differed significantly between headache types. Migraine and TANMH patients reported significantly more general signs and symptoms. Analysis of aura signs and symptoms showed that only two out of six groups were significantly more frequent in MA and TANMH patients. Visual aura symptoms were more frequent in MA and TANMH groups, where sensorial auras were reported to be the most frequent in the MA group. Our results showed that different type of headaches share common prodrome and aura signs and symptoms as well as the same trigger factors. We suggest that similar trigger factors may trigger similar mechanisms and may cause common preheadache signs and symptoms in all headache types.

Paraneoplastic neurological syndrome in systemic cancer.

Paraneoplastic syndrome refers to a group of disorders caused by or associated with cancers that are not direct effects of the primary tumor mass or a metastasis to the involved organs. Neurologically, the phrase describes a group of disorders that are diagnosed with increasing frequency in cancer patients. In this study, we investigated 36 patients with malignant diseases and various neurological paraneoplastic syndromes. Lung cancer is the most frequent malignancy associated with neurological paraneoplastic syndromes, and polyneuropathy is the most important manifestation among them.