Lancet neurology
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After a stroke, most patients have dysphagia, which can lead to aspiration pneumonia, malnutrition, and adverse functional outcomes. Protective interventions aimed at reducing these complications remain the cornerstone of treatment. Dietary adjustments and oral hygiene help mitigate the risk of aspiration pneumonia, and nutritional supplementation, including tube feeding, might be needed to prevent malnutrition. ⋯ Investigations have explored the use of pharmaceutical agents such as capsaicin and other Transient-Receptor-Potential-Vanilloid-1 (TRPV-1) sensory receptor agonists, which alter sensory perception in the pharynx. Neurostimulation techniques, such as transcranial direct current stimulation, repetitive transcranial magnetic stimulation, and pharyngeal electrical stimulation, might promote neuroplasticity within the sensorimotor swallowing network. Further advancements in the understanding of central and peripheral sensorimotor mechanisms in patients with dysphagia after a stroke, and during their recovery, will contribute to optimising treatment protocols.
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Migraine is a common neurological disorder with large burden in terms of disability for individuals and costs for society. Accurate diagnosis and effective treatments remain priorities. Understanding the genetic factors that contribute to migraine risk and symptom manifestation could improve individual management. ⋯ Some distinct, rare, familial migraine subtypes are caused by pathogenic variants in genes involved in ion transport and neurotransmitter release, suggesting an underlying vulnerability of the excitatory-inhibitory balance in the brain, which might be exacerbated by disruption of homoeostasis and lead to migraine. For more prevalent migraine subtypes, genetic studies have identified many susceptibility loci, implicating genes involved in both neuronal and vascular pathways. Genetic factors can also reveal the nature of relationships between migraine and its associated biomarkers and comorbidities and could potentially be used to identify new therapeutic targets and predict treatment response.
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Despite the success of disease-modifying treatments in relapsing multiple sclerosis, for many individuals living with multiple sclerosis, progressive disability continues to accrue. How to interrupt the complex pathological processes underlying progression remains a daunting and ongoing challenge. Since 2014, several immunomodulatory approaches that have modest but clinically meaningful effects have been approved for the management of progressive multiple sclerosis, primarily for people who have active inflammatory disease. ⋯ New classes of drug, such as Bruton tyrosine-kinase inhibitors, are coming to the end of their trial stages, several candidate neuroprotective compounds have been successful in phase 2 trials, and innovative approaches to remyelination are now also being explored in clinical trials. Work continues to define intermediate outcomes that can provide results in phase 2 trials more quickly than disability measures, and more efficient trial designs, such as multi-arm multi-stage and futility approaches, are increasingly being used. Collaborations between patient organisations, pharmaceutical companies, and academic researchers will be crucial to ensure that future trials maintain this momentum and generate results that are relevant for people living with progressive multiple sclerosis.
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The recent commercialisation of the first disease-modifying drugs for Alzheimer's disease emphasises the need for consensus recommendations on the rational use of biomarkers to diagnose people with suspected neurocognitive disorders in memory clinics. Most available recommendations and guidelines are either disease-centred or biomarker-centred. ⋯ We recommend first-line and, if needed, second-line testing for biomarkers according to the patient's clinical profile and the results of previous biomarker findings. This diagnostic workflow will promote consistency in the diagnosis of neurocognitive disorders across European countries.
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Migraine is a leading cause of disability worldwide. Despite the recent approval of several calcitonin gene-related peptide-targeted therapies, many people with migraine do not achieve satisfactory headache improvement with currently available therapies and there continues to be an unmet need for effective and tolerable migraine-specific treatments. ⋯ Animal and human studies show that these targets are expressed in regions of the CNS and peripheral nervous system that are involved in pain processing, indicating that these targets might be regarded as promising for the discovery of new migraine therapies. Future studies will require assessment of whether targets are suitable for therapeutic modulation, including assessment of specificity, affinity, solubility, stability, efficacy, and safety.