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Background: It is unknown whether new daily persistent headache (NDPH) is a single disorder or heterogenous group of disorders, and whether it is a unique disorder from chronic migraine and chronic tension-type headache. We describe a large group of patients with primary NDPH, compare its phenotype to transformed chronic daily headache (T-CDH), and use cluster analysis to reveal potential sub-phenotypes in the NDPH group., Methods: We performed a case-control study using prospectively collected clinical data in patients with primary NDPH and T-CDH (encompassing chronic migraine and chronic tension-type headache). We used logistic regression with propensity score matching to compare demographics, phenotype, comorbidities, and treatment responses between NDPH and T-CDH. We used K-means cluster analysis with Gower distance to identify sub-clusters in the NDPH group based on a combination of demographics, phenotype, and comorbidities., Results: We identified 366 patients with NDPH and 696 with T-CDH who met inclusion criteria. Patients with NDPH were less likely to be female (62.6% vs. 73.3%, p < 0.001). Nausea, vomiting, photophobia, phonophobia, motion sensitivity, vertigo, and cranial autonomic symptoms were all significantly less frequent in NDPH than T-CDH (p value for all < 0.001). Acute treatments appeared less effective in NDPH than T-CDH, and medication overuse was less common (16% vs. 42%, p < 0.001). Response to most classes of oral preventive treatments was poor in both groups. The most effective treatment in NDPH was doselupin in 45.7% patients (95% CI 34.8-56.5%). Cluster analysis identified three subgroups of NDPH. Cluster 1 was older, had a high proportion of male patients, and less severe headaches. Cluster 2 was predominantly female, had severe headaches, and few associated symptoms. Cluster 3 was predominantly female with a high prevalence of migrainous symptoms and headache triggers., Conclusions: Whilst there is overlap in the phenotype of NDPH and T-CDH, the differences in migrainous, cranial autonomic symptoms, and vulnerability to medication overuse suggest that they are not the same disorder. NDPH may be fractionated into three sub-phenotypes, which require further investigation., (© 2023. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Objective: To perform a systematic review and meta-analysis of the epidemiology, precipitants, phenotype, comorbidities, pathophysiology, treatment, and prognosis of primary new daily persistent headache., Methods: We searched PubMed/Medline, EMBASE, Cochrane, and clinicaltrials.gov until 31 December 2022. We included original research studies with any design with at least five participants with new daily persistent headache. We assessed risk of bias using National Institutes of Health Quality Assessment Tools. We used random-effects meta-analysis where suitable to calculate pooled estimates of proportions. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis compliant study is registered with PROSPERO (registration number CRD42022383561)., Results: Forty-six studies met inclusion criteria, predominantly case series, including 2155 patients. In 67% (95% CI 57-77) of cases new daily persistent headache has a chronic migraine phenotype, however new daily persistent headache has been found to be less likely than chronic migraine to be associated with a family history of headache, have fewer associated migrainous symptoms, be less vulnerable to medication overuse, and respond less well to injectable and neuromodulatory treatments., Conclusions: New daily persistent headache is a well described, recognisable disorder, which requires further research into its pathophysiology and treatment. There is a lack of high-quality evidence and, until this exists, we recommend continuing to consider new daily persistent headache a distinct disorder.

Background: The role of inflammation and cytokines in the pathophysiology of primary headache disorders is uncertain. We performed a systematic review and meta-analysis to synthesise the results of studies comparing peripheral blood cytokine levels between patients with migraine, tension-type headache, cluster headache, or new daily persistent headache (NDPH), and healthy controls; and in migraine between the ictal and interictal stages., Methods: We searched PubMed/Medline and Embase from inception until July 2022. We included original research studies which measured unstimulated levels of any cytokines in peripheral blood using enzyme-linked immunosorbent assay or similar assay. We assessed risk of bias using the Newcastle-Ottawa Quality Assessment Scale. We used random effects meta-analysis with inverse variance weighted average to calculate standardised mean difference (SMD), 95% confidence intervals, and heterogeneity for each comparison. This study is registered with PROSPERO (registration number CRD42023393363). No funding was received for this study., Results: Thirty-eight studies, including 1335 patients with migraine (32 studies), 302 with tension-type headache (nine studies), 42 with cluster headache (two studies), and 1225 healthy controls met inclusion criteria. Meta-analysis showed significantly higher interleukin (IL)-6 (SMD 1.07, 95% CI 0.40-1.73, p = 0.002), tumour necrosis factor (TNF)-α (SMD 0.61, 95% CI 0.14-1.09, p = 0.01), and IL-8 (SMD 1.56, 95% CI 0.03-3.09, p = 0.04), in patients with migraine compared to healthy controls, and significantly higher interleukin-1β (IL-1β) (SMD 0.34, 95% CI 0.06-0.62, p = 0.02) during the ictal phase of migraine compared to the interictal phase. Transforming growth factor (TGF)-β (SMD 0.52, 95% CI 0.18-0.86, p = 0.003) and TNF-α (SMD 0.64, 95% CI 0.33-0.96, p = 0.0001) were both higher in patients with tension-type headache than controls., Conclusions: The higher levels of the proinflammatory cytokines IL-6, IL-8 and TNF-α in migraine compared to controls, and IL-1β during the ictal stage, suggest a role for inflammation in the pathophysiology of migraine, however prospective studies are required to confirm causality and investigate the mechanisms for the increase in cytokine levels identified. Cytokines may also have a role in tension-type headache. Due a lack of data, no conclusions can be made regarding cluster headache or NDPH., (© 2023. The Author(s).)

Migraine affects over a billion people worldwide and brings with it a huge burden of disability. It is a disease which disproportionally affects the working age population which heightens its economic impact, both at the individual family level and the societal level. Women are significantly more affected by migraine at every age and in all social and geographical groups. At the most severe end of the spectrum, chronic migraine is associated with poorer overall physical and mental health as well as increased risk of unemployment and lower household income. Estimates of the incidence and prevalence of migraine vary with sex, race, ethnicity, geography, socioeconomic, and educational status, suggesting there are many factors at play. In many cases, it is not clear whether these factors are causative of migraine, the effects of migraine, or (as is most likely) a combination of both. Future studies should aim to clarify these links, so that modifiable factors can be addressed where possible and those at risk of developing chronic migraine might receive targeted treatment at an early stage., (Copyright © 2023 Elsevier B.V. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Abdominal migraine and cyclical vomiting syndrome (CVS) are characteristic syndromes which have overlapping characteristics with migraine but lack the cardinal symptom of headache. Both abdominal migraine and CVS are characterized by recurrent attacks of nausea, vomiting, and/or abdominal pain lasting hours to a few days, with symptom freedom between attacks. Both abdominal migraine and CVS typically occur in children and adolescents, who often go on to develop more typical migraine headaches when older, but may also present for the first time in adults. Due to their shared characteristics and association with migraine headaches, abdominal migraine and CVS are sometimes called "migraine equivalents," and their pathophysiology is assumed to overlap with migraine headache. This chapter describes what is known about the clinical characteristics, epidemiology, pathophysiology, and prognosis of abdominal migraine and CVS, and explores their relationship to migraine. We also review the existing evidence for the nonpharmacological management, acute treatment of attacks, and preventive treatments for both abdominal migraine and CVS., (Copyright © 2023 Elsevier B.V. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Headache is a common presentation of postural tachycardia syndrome, yet robust prevalence data is lacking., Objectives: To undertake a systematic review and meta-analysis to estimate the prevalence of headache disorders in postural tachycardia syndrome, and to explore the potential shared pathophysiological mechanisms that underpin these conditions as well as treatment options., Methods: Three databases were searched for publications evaluating prevalence of migraine (primary outcome) and general and orthostatic headache (secondary outcomes) in patients with postural tachycardia syndrome. Two independent reviewers selected studies and extracted data. A random-effects meta-analysis calculated the pooled prevalence of migraine in postural tachycardia syndrome. A narrative literature review explored the pathophysiology and treatment options for concurrent headache disorders and postural tachycardia syndrome., Results: Twenty-three articles met inclusion criteria. Estimated pooled prevalence of migraine in postural tachycardia syndrome was 36.8% (95% CI 2.9-70.7%). Various shared pathophysiological pathways for these conditions, as well as proposed treatment strategies, were identified. Limitations : Heterogeneity of study design, populations, and methodology for identifying headache disorders and postural tachycardia syndrome limited the generalisability of results., Conclusions: Migraine is a commonly reported comorbidity in POTS, however the true prevalence cannot be determined from the current literature. Further studies are required to assess this comorbidity and investigate the underlying mechanisms, as well as identify effective treatment strategies.

Objectives: New daily persistent headache (NDPH) is a subset of chronic headache where the pain is continuous from onset. Phenotypically it has chronic migraine or chronic tension type features. NDPH is considered to be highly refractory. Occipital nerve stimulation (ONS) has been used for treatment of refractory chronic migraine but there are no specific reports of its use for NDPH with migrainous features., Materials and Methods: Nine patients with NDPH with migrainous features were identified as having had ONS implants between 2007 and 2014 in a specialist unit with experience of using ONS in chronic migraine. Moderate to severe headache days were compared at baseline and follow-up. A positive response was defined as at least 30% reduction in monthly moderate to severe headache days., Results: Patients had suffered NDPH for a median of 8 years (range 3-16 years) and had failed a median of 11 previous treatments (range 8-15). After a median follow-up of 53 months (range 27-108 months), only a single patient showed a positive response to ONS. At no point did the cohort as a whole show any change in monthly moderate to severe headache days or disability scores., Conclusion: Our experience suggests that ONS is not effective in the treatment of NDPH with migrainous features even in centers with experience in treating chronic migraine with ONS. The difference in response rates of chronic migraine and NDPH with migrainous features supports the concept of a different pathophysiology to the two conditions., (© 2020 The Authors. Neuromodulation: Technology at the Neural Interface published by Wiley Periodicals LLC on behalf of International Neuromodulation Society.)