Background The presence of headache during the acute phase of COVID-19 could be associated with the innate response and the cytokine release. We aim to compare the cytokine and interleukin profile in hospitalized COVID-19 patients at the moment of admission with and without headache during the course of the disease. Methods An observational analytic study with a case control design was performed. Hospitalized patients from a tertiary hospital with confirmed COVID-19 disease were included. Patients were classified into the headache or the control group depending on whether they presented headache not better accounted for by another headache disorder other than acute headache attributed to systemic viral infection. Several demographic and clinical variables were studies in both groups. We determined the plasmatic levels of 45 different cytokines and interleukins from the first hospitalization plasma extraction in both groups. Results One hundred and four patients were included in the study, aged 67.4 (12.8), 43.3% female. Among them, 29 (27.9%) had headache. Patients with headache were younger (61.8 vs. 69.5 years, p = 0.005) and had higher frequency of fever (96.6 vs. 78.7%, p = 0.036) and anosmia (48.3% vs. 22.7%, p = 0.016). In the comparison of the crude median values of cytokines, many cytokines were different between both groups. In the comparison of the central and dispersion parameters between the two groups, GROa, IL-10, IL1RA, IL-21, IL-22 remained statistically significant. After adjusting the values for age, sex, baseline situation and COVID-19 severity, IL-10 remained statistically significant (3.3 vs. 2.2 ng/dL, p = 0.042), with a trend towards significance in IL-23 (11.9 vs. 8.6 ng/dL, p = 0.082) and PIGF1 (1621.8 vs. 110.6 ng/dL, p = 0.071). Conclusions The higher levels of IL-10 -an anti-inflammatory cytokine- found in our sample in patients with headache may be explained as a counteract of cytokine release, reflecting a more intense immune response in these patients.

Nummular headache (NH) is a primary headache characterized by superficial coin-shaped pain. NUMITOR (NCT 05475769) is an observational study evaluating the responder rate of preventive drugs in NH patients. The treatment response was assessed between weeks 8 and 12 compared with the baseline. Patients were included between February 2002 and October 2022. Demographic and clinical variables were assessed; treatment response was estimated by 50%, 30%, and 75% responder rates and treatment discontinuation due to inadequate tolerability. A total of 183 out of 282 patients fulfilled eligibility criteria and completed the study. Patients were aged 49.5 (standard deviation (SD): 16.8) years, and 60.7% were female. NH phenotype was a parietal circular pain of four centimeters’ diameter, moderate intensity, and oppressive quality. At baseline, patients had 25 (interquartile range) pain days per month. Preventive treatment was used by 114 (62.3%) patients. The highest 50% and 75% responder rates corresponded to onabotulinumtoxinA (62.5%, 47.5%), followed by gabapentin (43.7%, 35.2%). Oral preventive drugs were not tolerated by 12.9–25%. The present study provides class IV evidence of the effectiveness of oral preventive drugs and onabotulinumtoxinA in the treatment of primary NH. OnabotulinumtoxinA was the most effective and best-tolerated drug, positioning it as first-line treatment of NH.

BackgroundHeadache is a common manifestation of post-coronavirus disease (COVID) condition. We aimed to describe the need and effectiveness of acute and preventive medications in a series of 100 consecutive patients evaluated in a headache unit. MethodsObservational descriptive study with a series of cases design. Patients with confirmed COVID diagnosis that were referred due to headache following COVID were included. Patients were evaluated and treated by headache experts. The study included patients infected between March 1, 2020, and January 31, 2022. Demographic variables and clinical information at the moment of the treatment use were gathered. Response to treatment was evaluated according to pain freedom response two hours after the use of the acute medication, and in the case of the preventive medication, the 50%, 30% and 75% responder rates were calculated. ResultsPatients were aged 48.0 (standard deviation (SD): 12.4), were female (84%) and had prior history of headache (56%), anxiety (42%), sleep disorders (37%), and depression (26%). The mean time between the infection and the evaluation was 7.2 (SD: 4.0) months. The most common headache phenotype was holocranial (63%), frontal (48%), pressing (75%), of moderate intensity (7 out of 10), and accompanied by photophobia (58%). Acute medication was required by 93%, being paracetamol (46%) the most frequently used drug, followed by ibuprofen (44%). The drugs with the higher proportion of 2-hour pain-freedom response were dexketoprofen (58.8%), triptans (57.7%), ibuprofen (54.3%) and paracetamol (43.1%).Preventive treatment was required by 75% of patients. The most frequently used drugs were amitriptyline (66%), anesthetic blockades (18%) and onabotulinumtoxinA (11%). The drugs with the higher 50% responder rate were amitriptyline (45.5%), mirtazapine (50%) and anesthetic blockades (38.9%). The higher 75% responder rate was experienced following onabotulinutoxinA (18.2%) and the higher 30% responder rate was obtained following amitriptyline and onabotulinumtoxinA (72.7%). ConclusionsThe majority of patients required acute medication, with triptans and non-steroidal anti-inflammatory drugs being the therapies with the best results. Three quarters of patients required preventive medication. The most frequently used drug was amitriptyline, which obtained the best results. In some treatment-resistant patients, anesthetic blockades and onabotulinumtoxinA were also beneficial.

Introduction: The presence of headache during the acute phase of COVID-19 could be associated with the innate response and the cytokine release. We aim to compare the cytokine and interleukin profile by the time they were hospitalized in COVID-19 patients with and without headache during the course of the disease.Methods: An observational analytic study with a case control design was performed. Hospitalized patients from a tertiary hospital with confirmed COVID-19 disease were included. Patients were classified into the headache or the control group depending on whether they presented headache not better accounted for by another headache disorder other than acute headache attributed to systemic viral infection. Several demographic and clinical variables were studies in both groups. We determined the plasmatic levels of 45 different cytokines and interleukins from the first hospitalization plasma extraction in both groups. Results: One hundred and four patients were included in the study, aged 67.4 (12.8), 43.3% female. Among them, 29 (27.9%) had headache. Patients with headache were younger (61.8 vs. 69.5 years, p=0.005) and had higher frequency of fever (96.6 vs. 78.7%, p=0.036) and anosmia (48.3% vs. 22.7%, p=0.016). In the comparison of the crude median values of cytokines, many cytokines were different between both groups. In the comparison of the central and dispersion parameters between the two groups, GROa, IL-10, IL1RA, IL-21, IL-22 remained statistically significant. After adjusting the values for age, sex, baseline situation and COVID-19 severity, IL-10 remained statistically significant (3.3 vs. 2.2 ng/dL, p=0.042), with a trend towards signification in IL-23 (11.9 vs. 8.6 ng/dL, p=0.082) and PIGF1 (1621.8 vs. 110.6 ng/dL, p=0.071). Conclusion: The higher levels of IL-10-an anti-inflammatory cytokines- found in our sample in patients with headache may be explained as a counteract of cytokine release, reflecting a more efficient immune response in these patients