Presynaptic antiseizure medications - basic mechanisms and clues for their rational combinations.

Among clinically highly efficient antiseizure medications (ASMs) there are modifiers of the presynaptic release machinery. Of them, levetiracetam and brivaracetam show a high affinity to the synaptic vesicle protein type 2 A (SV2A), whereas pregabalin and gabapentin are selective ligands for the α2δ1 subunits of the voltage-gated calcium channels. In this paper, we present recent progress in understanding the significance of presynaptic release machinery in the neurochemical mechanisms of epilepsy and ASMs. Furthermore, we discuss whether the knowledge of the basic mechanisms of the presynaptically acting ASMs might help establish a rational polytherapy for drug-resistant epilepsy.

Sinonasal symptoms in migraine without aura: results from the cross-sectional 'Migraine in Poland' study.

Background: Migraine without aura (MwoA) is often mistaken for rhinosinusitis. The purpose of this study was to assess the prevalence of sinonasal symptoms, sinusitis-targeting medication use and burden of migraine in a large group of people with MwoA attacks accompanied by rhinologic symptoms. Methods: Data was collected in a cross-sectional online survey based on an adapted population-based study questionnaire. The analysis included the prevalence of rhinorrhea, mucopurulent nasal discharge, nasal congestion, facial pressure and tenderness to palpation, hyposmia/anosmia and osmophobia. Results: 1,679 (52.73%) MwoA people were identified among 3,225 respondents (women n = 2,809, 87.10%) aged 13-80 years (median age 39; standard deviation 10.4). 1004/1679 (59.8%) migraine patients reported one or more rhinologic symptoms and 341/1679 (20.3%) MwoA respondents had symptoms that met rhinosinusitis clinical diagnostic criteria during their headache attacks. In migraine patients, osmophobia was associated with hyposmia [n = 141 (12.7%) vs. n = 41 (7.2%); p = 0.001] and a sensation of unpleasant smells [n = 216 (19.4%) vs. n = 45 (8.5%); p = 0.001], while facial tenderness to palpation was associated with facial allodynia [n = 532 (50.4%) vs. n = 211 (33.9%); p < 0.001]. People with migraine accompanied by rhinosinusitis-like symptoms experienced more disease burden and used 'sinus medications' more often. Conclusion: MwoA patients with rhinosinusitis-like symptoms during migraine attacks require cautious assessment, especially that some symptoms seem to have little value in distinguishing between these disorders (i.e., facial tenderness, hyposmia), while many of these patients have a greater disease burden and therefore often choose medications targeting rhinologic instead of neurologic mechanisms.

Migraine symptoms, healthcare resources utilization and disease burden in a large Polish migraine cohort : Results from 'Migraine in Poland'-a nationwide cross-sectional survey.

BACKGROUND: The Migraine in Poland study is the first large scale nationwide cross-sectional online survey of symptoms, approaches to management, treatment patterns, quality of life, and sociodemographic characteristics of the Polish migraine patients' cohort, conducted from August 2021 to June 2022. METHODS: A cross-sectional online survey was designed based on the American Migraine Prevalence and Prevention (AMPP) Study. Participants were recruited through broad advertisement through various channels. The survey included questions allowing for the diagnosis of migraine without aura (MwoA) based on the third edition of the International Classification of Headache Disorders (ICHD-3). Moreover, the questionnaire assessed sociodemographic and headache features, comorbidities, consultation rates with medical professionals, as well as the use of abortive or preventive treatment, including non-pharmacological methods, psychological symptoms and the burden of migraine. RESULTS: A structured online questionnaire was submitted by 3225 respondents aged 13 to 80 (mean age 38.9, 87.1% women). In this group 1679 (52.7%) of participants fulfilled ICHD-3 diagnostic criteria for MwoA, which was in most cases (88.3%) confirmed by a medical professional in the past. In this group the average number of monthly headache days was 4.7, while 47.8% of participants had at least 4 migraine days per month. Mean Migraine Disability Assessment score was 42.65 (median 32). Among MwoA respondents, 1571 (93.6%) had consulted their headache with a medical professional in the past - mostly neurologists (n = 1450 (83.4%) and primary care physicians (n = 1393 (82.9%). In the MwoA cohort, 1553 (92.5%) of participants declared the current use of some form of treatment, although only 193 (11.5%) respondents were currently on preventive medications. The most prevalent comorbidities included: chronic rhinitis (37.1%), allergies (35.9%) and low blood pressure (26.9%). Anxiety (20.4%) and depression (21.3%) were highly prevalent among participants. CONCLUSIONS: People with migraine in Poland face similar difficulties as their peers in other countries. Despite relatively high access to neurologist consultations and good diagnosis accuracy, migraine still poses diagnostic and therapeutic difficulties. In this context, migraine undertreatment in Polish population must be underlined, especially in context of high disease burden.

The association between migraine and physical exercise.

BACKGROUND: There is an unmet need of pharmacological and non-pharmacological treatment options for migraine patients. Exercise can be used in the treatment of several pain conditions, including. However, what exact role exercise plays in migraine prevention is unclear. Here, we review the associations between physical exercise and migraine from an epidemiological, therapeutical and pathophysiological perspective. METHODS: The review was based on a primary literature search on the PubMed using the search terms "migraine and exercise". RESULTS: Low levels of physical exercise and high frequency of migraine has been reported in several large population-based studies. In experimental studies exercise has been reported as a trigger factor for migraine as well as migraine prophylaxis. Possible mechanisms for how exercise may trigger migraine attacks, include acute release of neuropeptides such as calcitonin gene-related peptide or alternation of hypocretin or lactate metabolism. Mechanisms for migraine prevention by exercise may include increased beta-endorphin, endocannabinoid and brain-derived neurotrophic factor levers in plasma after exercise. CONCLUSION: In conclusion, it seems that although exercise can trigger migraine attacks, regular exercise may have prophylactic effect on migraine frequency. This is most likely due to an altered migraine triggering threshold in persons who exercise regularly. However, the frequency and intensity of exercise that is required is still an open question, which should be addressed in future studies to delineate an evidence-based exercise program to prevent migraine in sufferers.