Circadian Features of Cluster Headache and Migraine: A Systematic Review, Meta-analysis, and Genetic Analysis.

BACKGROUND AND OBJECTIVES: Cluster headache and migraine have circadian features at multiple levels (cellular, systems, and behavioral). A thorough understanding of their circadian features informs their pathophysiologies. METHODS: A librarian created search criteria in MEDLINE Ovid, Embase, PsycINFO, Web of Science, and Cochrane Library. Two physicians independently performed the remainder of the systematic review/meta-analysis using Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. Separate from the systematic review/meta-analysis, we performed a genetic analysis for genes with a circadian pattern of expression (clock-controlled genes or CCGs) by cross-referencing genome-wide association studies (GWASs) of headache, a nonhuman primate study of CCGs in a variety of tissues, and recent reviews of brain areas relevant in headache disorders. Altogether, this allowed us to catalog circadian features at the behavioral level (circadian timing, time of day, time of year, and chronotype), systems level (relevant brain areas where CCGs are active, melatonin and corticosteroid levels), and cellular level (core circadian genes and CCGs). RESULTS: For the systematic review and meta-analysis, 1,513 studies were found, and 72 met the inclusion criteria; for the genetic analysis, we found 16 GWASs, 1 nonhuman primate study, and 16 imaging reviews. For cluster headache behavior, meta-analyses showed a circadian pattern of attacks in 70.5% (3,490/4,953) of participants across 16 studies, with a clear circadian peak between 21:00 and 03:00 and circannual peaks in spring and autumn. Chronotype was highly variable across studies. At the systems level, lower melatonin and higher cortisol levels were reported in cluster headache participants. At the cellular level, cluster headache was associated with core circadian genes CLOCK and REV-ERBα, and 5 of the 9 cluster headache susceptibility genes were CCGs. For migraine behavior, meta-analyses showed a circadian pattern of attacks in 50.1% (2,698/5,385) of participants across 8 studies, with a clear circadian trough between 23:00 and 07:00 and a broad circannual peak between April and October. Chronotype was highly variable across studies. At the systems level, urinary melatonin levels were lower in participants with migraine and even lower during an attack. At the cellular level, migraine was associated with core circadian genes CK1δ and RORα, and 110 of the 168 migraine susceptibility genes were CCGs. DISCUSSION: Cluster headache and migraine are highly circadian at multiple levels, reinforcing the importance of the hypothalamus. This review provides a pathophysiologic foundation for circadian-targeted research into these disorders. TRIAL REGISTRATION INFORMATION: The study was registered with PROSPERO (registration number CRD42021234238).

Pediatric-onset trigeminal autonomic cephalalgias: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: There are five headache disorders composing the trigeminal autonomic cephalalgias (cluster headache, paroxysmal hemicrania, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT), short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA), and hemicrania continua). Little is known about these disorders in the pediatric population. The objectives of this study are to report the full age ranges of pediatric trigeminal autonomic cephalalgias and to determine if pediatric-onset trigeminal autonomic cephalalgias display similar signs and symptoms as adult onset. METHODS: Search criteria in Medline Ovid, Embase, PsycINFO, and Cochrane Library were created by a librarian. The remainder of the steps were independently performed by two neurologists using PRISMA guidelines. Inclusion criteria for titles and abstracts were articles discussing cases of trigeminal autonomic cephalalgias with age of onset 18 or younger, as well as any epidemiological report on trigeminal autonomic cephalalgias (as age of onset data was often found in the results section but not in the title or abstract). Data extracted included age of onset, sex, and International Classification of Headache Disorders criteria for trigeminal autonomic cephalalgias (including pain location, duration, frequency, autonomic features, restlessness) and some migraine criteria (photophobia, phonophobia, and nausea). Studies that did not meet full criteria for trigeminal autonomic cephalalgias were examined separately as "atypical trigeminal autonomic cephalalgias"; secondary headaches were excluded from this category. RESULTS: In all, 1788 studies were searched, 86 met inclusion criteria, and most (56) examined cluster headache. In cluster headache, onset occurred at every pediatric age (range 1-18 years) with a full range of associated features. Autonomic and restlessness features were less common in pediatric patients, while migrainous features (nausea, photophobia, and phonophobia) were found at similar rates. The sex ratio of pediatric-onset cluster headache (1.8, 79 male and 43 female) may be lower than that of adult-onset cluster headache. Data for other trigeminal autonomic cephalalgias, while more limited, displayed most of the full range of official criteria. The data for atypical trigeminal autonomic cephalalgias were also limited, but the most common deviations from the official criteria were abnormal frequencies and locations of attacks. CONCLUSIONS: Trigeminal autonomic cephalalgias can start early in life and have similar features to adult-onset trigeminal autonomic cephalalgias. Specifically, pediatric-onset cluster headache patients display the full range of each criterion for cluster headache (except maximum frequency of six instead of eight attacks per day). However, cranial autonomic features and restlessness occur at a lower rate in pediatrics. Additional information is needed for the other trigeminal autonomic cephalalgias. As for expanding the ICHD-3 criteria for pediatric-onset trigeminal autonomic cephalalgias, we have only preliminary data from atypical cases, which suggests that the frequency and location of attacks sometimes extend beyond the official criteria.Trial Registration: This study was registered as a systematic review in PROSPERO (registration number CRD42020165256).

Leiomiosarcoma de colon / Colonic leiomyosarcoma

Se presenta una observación de leiomiosarcoma de colon izquierdo, posiblemente la primera de este tipo en la literatura nacional. Se hacen consideraciones sobre los diferentes problemas diagnósticos y terapéuticos en base a una extensa revisión bibliográfica