Holmbergmerrill8183
Autoimmune encephalitis (AE) refers to immune-mediated neurological syndromes often characterised by the detection of pathogenic autoantibodies in serum and/or cerebrospinal fluid which target extracellular epitopes of neuroglial antigens. There is increasing evidence these autoantibodies directly modulate function of their antigens in vivo. Early treatment with immunotherapy improves outcomes. Yet, these patients commonly exhibit chronic disability. Importantly, optimal therapeutic strategies at onset and during escalation remain poorly understood. In this review of a rapidly emerging field, we evaluate recent studies on larger cohorts, registries, and meta-analyses to highlight existing evidence for contemporary therapeutic approaches in AE.
We highlight acute and long-term treatments used in specific AE syndromes, exemplify how understanding disease pathogenesis can inform precision therapy and outline challenges of defining disability outcomes in AE.
Early first-line immunotherapies, including cortions between international multicentre cohorts, and enable future meta-analyses with the aim of developing evidence-based therapeutic guidelines.
The coronavirus disease 2019 (COVID) pandemic has resulted in significant mortality and morbidity globally. SR18662 research buy Patients who survive infection may develop continuing disease collectively known as the postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC), which includes neurologic symptoms especially fatigue and cognitive impairment. The pathogenic mechanisms driving PASC are unknown although a postinfectious process, persistent infection, or lasting pathophysiological changes that occur during acute infection are all suspected to contribute.
Here we review the current evidence underlying potential pathogenic mechanisms of the neurological complications of PASC with particular emphasis on the evidence for postinfectious immune processes and viral persistence.
Immune dysregulation favoring persistent inflammation, including neuroinflammation and enhanced autoimmunity, are present in patients with COVID and likely contribute to the development of PASC. Limited evidence of viralns occur with greater frequency in patients with COVID and may contribute to the development of PASC. Future research is needed to fully understand the pathophysiological mechanisms driving PASC.
Research on migraine usually focuses on the headache; however, accumulating evidence suggests that migraine not only changes the somatosensory system for nociception (pain), but also the other modalities of perception, such as visual, auditory or tactile sense. More importantly, the multisensory changes exist beyond the headache (ictal) phase of migraine and show cyclic changes, suggesting a central generator driving the multiple sensory changes across different migraine phases. This review summarizes the latest studies that explored the cyclic sensory changes of migraine.
Considerable evidence from recent neurophysiological and functional imaging studies suggests that alterations in brain activation start at least 48 h before the migraine headache and outlast the pain itself for 24 h. Several sensory modalities are involved with cyclic changes in sensitivity that peak during the ictal phase.
In many ways, migraine represents more than just vascular-mediated headaches. Migraine alters the propagation of sensory information long before the headache attack starts.
In many ways, migraine represents more than just vascular-mediated headaches. Migraine alters the propagation of sensory information long before the headache attack starts.
In this review, we illustrate and discuss the recent findings regarding the epidemiology and pathophysiology of migraine triggers and their implications in clinical practice.
Data from the literature suggest that individual triggers fail to provoke migraine attack in experimental settings. It is therefore possible that more triggers acting in combination are needed to induce an attack by promoting some degree of brain dysfunction and thus increasing the vulnerability to migraine. Caution is however needed, because some of the factors rated as triggers by the patients may actually be a component of the clinical picture of migraine attacks.
Trigger factors of migraine are endogenous or exogenous elements associated with an increased likelihood of an attack in a short period of time and are reported by up to 75.9% of patients. Triggers must be differentiated from premonitory symptoms that precede the headache phase but do not have a causative role in attack provocation, being rather the very first manifestations of the attack. Identification of real triggers is an important step in the management of migraine. Vice versa, promoting an active avoiding behaviour toward factors whose role as triggers is not certain would be ineffective and even frustrating for patients.
Trigger factors of migraine are endogenous or exogenous elements associated with an increased likelihood of an attack in a short period of time and are reported by up to 75.9% of patients. Triggers must be differentiated from premonitory symptoms that precede the headache phase but do not have a causative role in attack provocation, being rather the very first manifestations of the attack. Identification of real triggers is an important step in the management of migraine. Vice versa, promoting an active avoiding behaviour toward factors whose role as triggers is not certain would be ineffective and even frustrating for patients.
Medication overuse headache (MOH) affects more than 60 million individuals worldwide causing enormous personal and social burden. Only repurposed drugs are available for MOH that share limited evidence for efficacy. The preclinical data suggesting that activation of the calcitonin gene-related peptide (CGRP) pathway is involved in headache chronification along with clinical evidence that monoclonal antibodies targeting CGRP (anti-CGRP mAbs) have good efficacy in preventing chronic migraine, triggered this review that aims to summarize the current data on the effectiveness and safety of mAbs against CGRP in MOH.
Post hoc analyses of phase-3 trials of erenumab, fremanezumab, galcanezumab, and eptinezumab for the prevention of chronic migraine revealed that patients with MOH benefit from the treatment over placebo. Several real-world studies confirm the efficacy of erenumab and galcanezumab in patients with MO. However, all published trials evaluated treatments in patients with chronic migraine with MO collectively, not in patients with MOH exclusively.
The available data indicate that anti-CGRP mAbs represent a good mechanism-based and disease-specific therapeutical option with for MOH as long as detoxification and additional nonpharmaceutical interventions are operated. Future research should focus on long-term-controlled trials in MOH populations exclusively.
The available data indicate that anti-CGRP mAbs represent a good mechanism-based and disease-specific therapeutical option with for MOH as long as detoxification and additional nonpharmaceutical interventions are operated. Future research should focus on long-term-controlled trials in MOH populations exclusively.
The aim of this study was to provide an overview of clinical studies on calcitonin gene-related peptide (CGRP) measurements in body fluids of migraine patients and to discuss the validity of CGRP measurement as a clinical biomarker of migraine.
Several studies have reported increased CGRP levels in venous blood, saliva and tear fluid of migraine patients compared with healthy controls and in migraine patients during attacks compared with the interictal state, suggesting that CGRP may be a feasible biomarker of migraine. However, the findings of studies investigating CGRP levels in migraine patients are generally conflicting and measurements of CGRP levels are challenged by several methodological issues. Reported differences in CGRP levels between patients with chronic migraine relative to episodic migraine have also been inconsistent. There is also a well documented involvement of CGRP in several nonmigraine pain disorders, including cluster headache and common pain conditions such as osteoarthritis.
Current evidence does not justify the usage of CGRP levels as a biomarker for diagnosing migraine or for determining the severity of the disease in individual patients. However, CGRP measurements could prove useful in the future as clinically relevant biomarkers for predicting the response to therapy, including anti-CGRP migraine drugs.
Current evidence does not justify the usage of CGRP levels as a biomarker for diagnosing migraine or for determining the severity of the disease in individual patients. However, CGRP measurements could prove useful in the future as clinically relevant biomarkers for predicting the response to therapy, including anti-CGRP migraine drugs.
The pathophysiological understanding of cluster headache has evolved significantly over the past years. Although it is now well known that the trigeminovascular system, the parasympathetic system and the hypothalamus play important roles in its pathomechanism, we increasingly understand the functional role several neurotransmitters and hormones play in the communication between these structures.
This work will give an overview of the current understanding of the role of calcitonin gene-related peptide, vasoactive intestinal peptide, pituitary adenylate cyclase-activating peptide, melatonin and orexins in cluster headache. On the basis of recent evidence, this study will also review the relevance of the monoclonal calcitonin gene-related peptide antibody galcanezumab as well as the sleep-regulating hormone melatonin in the treatment of cluster headache.
Herein, we aim to review the basic mechanisms implicated in the pathophysiology of cluster headache and how the increased mechanistic understanding may lead to the discovery of novel therapeutic targets.
Herein, we aim to review the basic mechanisms implicated in the pathophysiology of cluster headache and how the increased mechanistic understanding may lead to the discovery of novel therapeutic targets.
The underlying mechanisms of migraine are complex and heterogenous. Advances in neuroimaging techniques during the past few decades have contributed to our understanding of migraine pathophysiology. Brain function in migraine patients has been widely explored using functional MRI (fMRI). This review will highlight the major fMRI findings that characterize the different phases of migraine.
The migraine attack starts with hypothalamic hyperexcitability and early reorganization of the common ascending pain and central trigeminovascular pathways. Moreover, the visual cortex becomes hyperexcitable during the aura phase. During the headache phase, further disruptions of the pontine, thalamic, sensorimotor and visual networks occur, although the hypothalamic activity and connectivity normalizes. The visual cortex remains hyperexcitable during the postdromal phase. Asymptomatic migraine patients can also experience functional alternations of pain and visual processing brain areas. At present, the heterogeneity of the asymptomatic phase and fMRI findings make it difficult to find common denominator.
