The long-term replacement therapy with the dopamine (DA) precursor 3,4-dihydroxy-l-phenylalanine (L-DOPA) is a milestone in the treatment of Parkinson's disease (PD). Although this drug precursor can be metabolized into the active neurotransmitter DA throughout the brain, its therapeutic benefit is due to restoring extracellular DA levels within the dorsal striatum, which lacks endogenous DA as a consequence of the neurodegenerative process induced by the disease. In the early phases of PD, L-DOPA treatment is able to restore both long-term depression (LTD) and long-term potentiation (LTP), two major forms of corticostriatal synaptic plasticity that are altered by dopaminergic denervation. However, unlike physiological DA transmission, this therapeutic approach in the advanced phase of the disease leads to abnormal peaks of DA, non-synaptically released, which are supposed to trigger behavioural sensitization, namely L-DOPA-induced dyskinesia. This condition is characterized by a loss of synaptic depotentiation, an inability to reverse previously induced LTP. In the advanced stages of PD, L-DOPA can also induce non-motor fluctuations with cognitive dysfunction and neuropsychiatric symptoms such as compulsive behaviours and impulse control disorders. Although the mechanisms underlying the role of L-DOPA in both motor and behavioural symptoms are still incompletely understood, recent data from electrophysiological and imaging studies have increased our understanding of the function of the brain areas involved and of the mechanisms implicated in both therapeutic and adverse actions of L-DOPA in PD patients.

We here present evidence-based guidelines for the pharmacological treatment of migraine. These guidelines, created by the Italian Society for the Study of Headache and the International Headache Society, aim to offer clear, actionable recommendations to healthcare professionals. They incorporate evidence-based recommendations from randomized controlled trials and expert-based opinions. The guidelines follow the Grading of Recommendations, Assessment, Development and Evaluation approach for assessing the quality of evidence. The guideline development involved a systematic review of literature across multiple databases, adherence to Cochrane review methods, and a structured framework for data extraction and interpretation. Although the guidelines provide a robust foundation for migraine treatment, they also highlight gaps in current research, such as the paucity of head-to-head drug comparisons and the need for long-term outcome studies. These guidelines serve as a resource to standardize migraine treatment and promote high-quality care across different healthcare settings.

We here present evidence-based guidelines for the pharmacological treatment of migraine. These guidelines, created by the Italian Society for the Study of Headache and the International Headache Society, aim to offer clear, actionable recommendations to healthcare professionals. They incorporate evidence-based recommendations from randomized controlled trials and expert-based opinions. The guidelines follow the GRADE approach for assessing the quality of evidence. The guideline development involved a systematic review of literature across multiple databases, adherence to Cochrane review methods, and a structured framework for data extraction and interpretation. Although the guidelines provide a robust foundation for migraine treatment, they also highlight gaps in current research, such as the paucity of head-to-head drug comparisons and the need for long-term outcome studies. These guidelines serve as a resource to standardize migraine treatment and promote high-quality care across different healthcare settings.

Background: Migraine has been associated with an increased risk for ischemic stroke and other cardiovascular (CV) events, including angina, myocardial infarction, and CV death, but the mechanisms that link migraine to CV disease remain uncertain. We hypothesized that aortic pulse wave velocity (PWV), a direct measure of aortic stiffness and an independent predictor of stroke and CV disease, may be increased in young migraineurs with no overt CV disease or major CV risk factors. Methods: We studied 60 subjects with migraine (age 33 ± 8 years, 85% women, blood pressure 119/74 ± 11/9 mm Hg) and 60 age-, sex-, and blood pressure–matched healthy control subjects. In all participants, carotid–femoral PWV and aortic augmentation index were determined by applanation tonometry. Cases and controls were free from overt CV disease, diabetes, and major CV risk factors. Results: Subjects with migraine had a higher aortic PWV (7.6 ± 1.2 vs 6.4 ± 1.1 m×s⁻¹, p < 0.001) and aortic augmentation (heart rate–adjusted augmentation index, 0.17 ± 0.13 vs 0.08 ± 0.15, p < 0.001) than matched control subjects. Migraine patients with aura (n = 17) had higher aortic PWV than those without aura (n = 43; 8.2 ± 1.2 vs 7.4 ± 1.1 m×s⁻¹, p = 0.027). Age, mean arterial pressure as a measure of distending pressure, and migraine (all p < 0.05) independently predicted aortic PWV when a consistent number of CV risk factors was simultaneously controlled for. Conclusions: Migraine is independently associated with increased aortic stiffness and enhanced pressure wave reflection. This finding, obtained in young subjects without major CV risk factors, may represent one possible mechanism underlying the increased CV risk in migraine patients.