Headache onset after vaccination against SARS-CoV-2: a systematic literature review and meta-analysis.

BACKGROUND: Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are used to reduce the risk of developing Coronavirus Disease 2019 (COVID-19). Despite the significant benefits in terms of reduced risk of hospitalization and death, different adverse events may present after vaccination: among them, headache is one of the most common, but nowadays there is no summary presentation of its incidence and no description of its main features. METHODS: We searched PubMed and EMBASE covering the period between January 1st 2020 and August 6th, 2021, looking for record in English and with an abstract and using three main search terms (with specific variations): COVID-19/SARS-CoV-2; Vaccination; headache/adverse events. We selected manuscript including information on subjects developing headache after injection, and such information had to be derived from a structured form (i.e. no free reporting). Pooled estimates and 95% confidence intervals were calculated. Analyses were carried out by vaccine vs. placebo, by first vs. second dose, and by mRNA-based vs. "traditional" vaccines; finally, we addressed the impact of age and gender on post-vaccine headache onset. RESULTS: Out of 9338 records, 84 papers were included in the review, accounting for 1.57 million participants, 94% of whom received BNT162b2 or ChAdOx1. Headache was generally the third most common AE: it was detected in 22% (95% CI 18-27%) of subjects after the first dose of vaccine and in 29% (95% CI 23-35%) after the second, with an extreme heterogeneity. Those receiving placebo reported headache in 10-12% of cases. No differences were detected across different vaccines or by mRNA-based vs. "traditional" ones. None of the studies reported information on headache features. A lower prevalence of headache after the first injection of BNT162b2 among older participants was shown. CONCLUSIONS: Our results show that vaccines are associated to a two-fold risk of developing headache within 7 days from injection, and the lack of difference between vaccine types enable to hypothesize that headache is secondary to systemic immunological reaction than to a vaccine-type specific reaction. Some descriptions report onset within the first 24 h and that in around one-third of the cases, headache has migraine-like features with pulsating quality, phono and photophobia; in 40-60% of the cases aggravation with activity is observed. The majority of patients used some medication to treat headache, the one perceived as the most effective being acetylsalicylic acid.

Development and validation of the ID-EC - the ITALIAN version of the identify chronic migraine.

BACKGROUND: Case-finding tools, such as the Identify Chronic Migraine (ID-CM) questionnaire, can improve detection of CM and alleviate its significant societal burden. We aimed to develop and validate the Italian version of the ID-CM (ID-EC) in paper and as a smart app version in a headache clinic-based setting. METHODS: The study investigators translated and adapted to the Italian language the original ID-CM questionnaire (ID-EC) and further implemented it as a smart app. The ID-EC was tested in its paper and electronic version in consecutive patients referring to 9 Italian tertiary headache centers for their first in-person visit. The scoring algorithm of the ID-EC paper version was applied by the study investigators (case-finding) and by patients (self-diagnosis), while the smart app provided to patients automatically the diagnosis. Diagnostic accuracy of the ID-EC was assessed by matching the questionnaire results with the interview-based diagnoses performed by the headache specialists during the visit according to the criteria of International Classification of Headache Disorders, III edition, beta version. RESULTS: We enrolled 531 patients in the test of the paper version of ID-EC and 427 in the validation study of the smart app. According to the clinical diagnosis 209 patients had CM in the paper version study and 202 had CM in the smart app study. 79.5% of patients returned valid paper questionnaires, while 100% of patients returned valid and complete smart app questionnaires. The paper questionnaire had a 81.5% sensitivity and a 81.1% specificity for case-finding and a 30.7% sensitivity and 90.7% specificity for self-diagnosis, while the smart app had a 64.9% sensitivity and 90.2% specificity. CONCLUSIONS: Our data suggest that the ID-EC, developed and validated in tertiary headache centers, is a valid case-finding tool for CM, with sensitivity and specificity values above 80% in paper form, while the ID-EC smart app is more useful to exclude CM diagnosis in case of a negative result. Further studies are warranted to assess the diagnostic accuracy of the ID-EC in general practice and population-based settings.

Magnetic Resonance-guided Focused Ultrasound thalamotomy for refractory neuropathic pain: a systematic review and critical appraisal of current knowledge.

Background: Magnetic Resonance-guided Focused Ultrasound (MRgFUS) is an innovative therapeutical approach for medically refractory tremor. It is currently under investigation for other neurological diseases including refractory neuropathic pain (NP). Objective: The objective of this systematic review is to analyze available evidence about the effectiveness and safety profile of MRgFUS in the treatment of refractory NP. Methods: Eligible studies were identified by searching published studies in PubMed and Scopus databases from inception to December 2022 and by identifying ongoing studies registered on the clinicaltrials.gov website. The study was registered in PROSPERO (ID: CRD42021277154). Results: We found three published observational studies and nine ongoing studies. In published studies, the involved population ranged from 8 to 46 patients with overall 66 patients being included with NP or trigeminal neuralgia. The target lesion was in the posterior part of the central lateral nucleus of the thalamus, bilaterally. Outcomes were assessed at different times through the Visual Analog Scale, showing a variable degree of improvement. Adverse events were rare, mild, and transient (vertigo, paresthesias, and dysesthesias) with intracerebral bleeding being reported as major adverse event in one case only. Among ongoing studies, we found three prospective, randomized, sham-controlled, crossover trials (RCTs) and six observational studies. Inclusion criteria are previous failure of more than three pharmacological treatments and NP duration longer than 6 months. The thalamus is the main proposed target and measured outcomes are accuracy of the procedure and pain relief, with a follow-up period ranging from 1 week to 1 year. Conclusion: This systematic review suggests that, although high-quality studies are lacking, available evidence endorses the effectiveness and safety of MRgFUS in the management of NP. Ongoing RCTs will provide more robust data to understand benefits and risks of the procedure. Registration: PROSPERO (ID: CRD42021277154).

Retreating migraine patients in the second year with monoclonal antibodies anti-CGRP pathway: the multicenter prospective cohort RE-DO study.

BACKGROUND: The outcome of migraine patients retreated with monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (anti-CGRP) or its receptor (anti-CGRPr) is not completely known. METHODS: This multicentric prospective observational cohort study assessed monthly migraine days (MMDs), migraine acute medication intake (MAMI), and HIT-6 at baseline, after 90-112 days (Rev-1), after 84-90 days since Rev-1 (Rev-2) and 30 days after the last injection of anti-CGRP/CGRPr mAbs (Year-end), in the first and the second year after a discontinuation period. RESULTS: We enrolled 226 patients (79.6% with chronic migraine; 55.3% on erenumab and 44.7% on galcanezumab or fremanezumab). MMDs, MAMI, and HIT-6-did not differ at the respective first and second-year evaluations in the entire cohort, and comparing anti-CGRP with anti-CGRPr Abs. MMDs (18.1 ± 7.8 vs. 3.4 ± 7.8), MAMI (26.7 ± 28.3 vs.17.7 ± 17.2), and HIT-6 scores (63.1 ± 5.9 vs. 67.1 ± 10.3) were lower in the second year than in the pre-treatment baseline (consistently, p < 0.0001). Second-year baseline MMDs were lower in patients on anti-CGRP mAbs (p = 0.001) and with lower pre-treatment baseline MMDs (p ≤ 0.001). CONCLUSION: Anti-CGRP/CGRPr mAbs are effective in the second as in the first year. The use of anti-CGRP or CGRPr mAbs influenced the second-year baseline MMDs, but their effectiveness did not differ during the two treatment years.