Galcanezumab add-on in refractory cluster headache. A case series.

Cluster headache (CH), a highly disabling condition, lacks disease-specific, mechanism-based prophylactic treatment. Galganezumab, a monoclonal antibody targeting the calcitonin gene-related peptide, reduced the weekly attacks of CH in one randomized, placebo-controlled trial for the prevention of episodic CH (eCH), but this effect was not detected in people with chronic CH (cCH). In this case series, we systematically monitored the efficacy and safety outcomes of adjunctive therapy in 11 people with refractory CH (failure of ≥ 3 prophylactic treatments; eCH  = 5, cCH,  = 6) who received galcanezumab (120-360 mg monthly) for 3 consecutive months.

Comparative effects of drug interventions for the acute management of migraine episodes in adults: systematic review and network meta-analysis.

Objective: To compare all licensed drug interventions as oral monotherapy for the acute treatment of migraine episodes in adults.

Design: Systematic review and network meta-analysis.

Data Sources: Cochrane Central Register of Controlled Trials, Medline, Embase, ClinicalTrials.

Onabotulinumtoxina in the Prevention of Migraine in Pediatric Population: A Systematic Review.

Migraine is a leading cause of disability worldwide, yet it remains underrecognized and undertreated, especially in the pediatric and adolescent population. Chronic migraine occurs approximately in 1% of children and adolescents requiring preventive treatment. Topiramate is the only FDA-approved preventative treatment for children older than 12 years of age, but there is conflicting evidence regarding its efficacy.

European Headache Federation (EHF) critical re-appraisal and meta-analysis of oral drugs in migraine prevention - part 4: propranolol.

Objective: The aim of this paper is to critically re-appraise the published trials assessing propranolol for migraine prophylaxis.

Methods: We report methods and results following the Preferred Reporting Items for Systematic Reviews (PRISMA), by searching MEDLINE, EMBASE, Cochrane CENTRAL, and ClinicalTrials.gov for randomized trials of pharmacologic treatments for migraine prophylaxis.

Depression and Anxiety Symptoms in Headache Disorders: An Observational, Cross-Sectional Study.

Background: Headache disorders have been associated with anxiety and depressive disorders. The aim of this study was to assess symptoms of anxiety and depression in a large sample of individuals with different headache disorders (HDs) in order to determine whether their frequency differs by headache type.

Methods: Consecutive individuals with headache attending a headache outpatient clinic were interviewed with the HAM-D and HAM-A, along with age, sex, and education matched non-headache individuals.

Headaches and facial pain attributed to SARS-CoV-2 infection and vaccination: a systematic review.

Background And Purpose: The aim was to provide insights to the characteristics of headache in the context of COVID-19 on behalf of the Headache Scientific Panel and the Neuro-COVID-19 Task Force of the European Academy of Neurology (EAN) and the European Headache Federation (EHF).

Methods: Following the Delphi method the Task Force identified six relevant questions and then conducted a systematic literature review to provide evidence-based answers and suggest specific diagnostic criteria.

Results: No data for facial pain were identified in the literature search.

European Headache Federation (EHF) critical reappraisal and meta-analysis of oral drugs in migraine prevention - part 3: topiramate.

Objective: Topiramate is a repurposed first-line treatment for migraine prophylaxis. The aim of this systematic review and meta-analysis is to critically re-appraise the existing evidence supporting the efficacy and tolerability of topiramate.

Methods: A systematic search in MEDLINE, EMBASE, Cochrane CENTRAL, and ClinicalTrials.

European Headache Federation (EHF) critical re-appraisal and meta-analysis of oral drugs in migraine prevention-part 2: flunarizine.

Objective: Novel disease-specific and mechanism-based treatments sharing good evidence of efficacy for migraine have been recently marketed. However, reimbursement by insurers depends on treatment failure with classic anti-migraine drugs. In this systematic review and meta-analysis, we aimed to identify and rate the evidence for efficacy of flunarizine, a repurposed, first- or second-line treatment for migraine prophylaxis.

Second messenger signalling bypasses CGRP receptor blockade to provoke migraine attacks in humans.

There are several endogenous molecules that can trigger migraine attacks when administered to humans. Notably, calcitonin gene-related peptide (CGRP) has been identified as a key player in a signalling cascade involved in migraine attacks, acting through the second messenger cyclic adenosine monophosphate (cAMP) in various cells, including intracranial vascular smooth muscle cells. However, it remains unclear whether intracellular cAMP signalling requires CGRP receptor activation during a migraine attack in humans.

The effect of Lu AG09222 on PACAP38- and VIP-induced vasodilation, heart rate increase, and headache in healthy subjects: an interventional, randomized, double-blind, parallel-group, placebo-controlled study.

Background: Pituitary adenylate cyclase-activating polypeptide (PACAP), structurally related to vasoactive intestinal peptide (VIP), is one of the important mediators in the pathogenesis of migraine and is known to dilate cranial arteries and induce headache and migraine. Our objective was to determine whether Lu AG09222-an investigational humanized monoclonal antibody directed against PACAP ligand-would inhibit the PACAP-signaling cascade by abolishing its vasodilatory and headache-inducing abilities.

Methods: In a randomized, double-blind, parallel-group, single-dose, placebo-controlled study of Lu AG09222, healthy volunteers aged 18-45 years without history of headache disorders were randomly allocated to three treatment sequences (1:2:2) on two experimental infusion visits with 9 ± 3 days' interval: placebo + saline + saline (n = 5), placebo + PACAP38 + VIP (n = 10), and Lu AG09222 + PACAP38 + VIP (n = 10).

The comparative effectiveness of migraine preventive drugs: a systematic review and network meta-analysis.

Objective: While there are several trials that support the efficacy of various drugs for migraine prophylaxis against placebo, there is limited evidence addressing the comparative safety and efficacy of these drugs. We conducted a systematic review and network meta-analysis to facilitate comparison between drugs for migraine prophylaxis.

Methods: We searched MEDLINE, EMBASE, CENTRAL, and clinicaltrials.

Plasma levels of VIP are not elevated during PACAP- and VIP-induced cluster headache attacks: an exploratory study.

Background: Pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP) provoked cluster headache attacks in individuals with episodic cluster headache during their active phase and individuals with chronic cluster headache. In this study, we investigated whether infusions of PACAP and VIP caused alterations in plasma levels of VIP and their potential contribution to induced cluster headache attacks.

Methods: Participants received either PACAP or VIP infusion for 20 min on 2 separate days with an interval of at least 7 days in between.

European Headache Federation (EHF) critical re-appraisal and meta-analysis of oral drugs in migraine prevention-part 1: amitriptyline.

Objective: The aim of this paper is to critically re-appraise the published trials assessing amitriptyline for migraine prophylaxis.

Methods: We report our methods and results following the Preferred Reporting Items for Systematic Reviews (PRISMA), by searching MEDLINE, EMBASE, Cochrane CENTRAL, and ClinicalTrials.gov for randomized trials of pharmacologic treatments for migraine prophylaxis.

European Headache Federation (EHF) consensus on the definition of effective treatment of a migraine attack and of triptan failure.

Background: Triptans are migraine-specific acute treatments. A well-accepted definition of triptan failure is needed in clinical practice and for research. The primary aim of the present Consensus was to provide a definition of triptan failure.

Visual snow: A systematic review and a case series.

Background: Visual Snow Syndrome is a recently recognized neurological condition presenting, continuous, tiny dots across the entire visual field, accompanied by nyctalopia, photophobia and palinopsia that persist for months. It may be part of migraine aura spectrum, yet its definition is still questionable. Diagnostic criteria for Visual Snow Syndrome are included in the supplemental material of ICHD-3.

European Headache Federation guideline on the use of monoclonal antibodies targeting the calcitonin gene related peptide pathway for migraine prevention - 2022 update.

Background: A previous European Headache Federation (EHF) guideline addressed the use of monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway to prevent migraine. Since then, randomized controlled trials (RCTs) and real-world evidence have expanded the evidence and knowledge for those treatments. Therefore, the EHF panel decided to provide an updated guideline on the use of those treatments.

Nocebo-Prone Behavior Associated with SARS-CoV-2 Vaccine Hesitancy in Healthcare Workers.

Among healthcare workers (HCWs), SARS-CoV-2 vaccine hesitancy may be linked to a higher susceptibility to nocebo effects, i.e., adverse events (AEs) experienced after medical treatments due to negative expectations.

Monoclonal Antibodies Targeting CGRP: From Clinical Studies to Real-World Evidence-What Do We Know So Far?

Now more than ever is the time of monoclonal antibody use in neurology. In headaches, disease-specific and mechanism-based treatments existed only for symptomatic management of migraines (i.e.

Safety and tolerability evaluation of erenumab for the preventive treatment of migraine.

: Erenumab, a monoclonal antibody targeting the receptor of calcitonin gene related peptide (CGRP), is the first disease-specific and mechanism-based treatment approved for the prevention of migraine. Although the safety and tolerability data from randomized trials are clear, the physiological effects of CGRP rise reasonable concerns. We aimed to evaluate the current evidence for safety and tolerability related to erenumab use in migraine.

Current advances in the management of cluster headaches.

: Cluster headache (CH) is probably the most severe idiopathic pain condition, yet its current medical management remains poor.: Only repurpose medicines are currently in use for the prevention of CH, partially because the pathophysiology of the condition is still elusive. In this article we performed a systematic review to evaluate the evidence for efficacy of the currently available or emerging treatments for CH.