Cluster Headache and the Comprehension Paradox

Patients with primary headache disorders such as cluster headache cycle between being entirely healthy and almost completely incapacitated. Sick leave or reduced performance due to headache attacks demands flexibility by their social counterparts. The objective of this study is to test the hypothesis that headache patients cause frustration that grows with the times colleagues have to take over their work. In this study, we analysed cluster headache patients’ answers to an online questionnaire. Participants self-reported their number of sick days, the number of days on which leisure activities were missed and whether they felt understood by colleagues and family. We then investigated the correlation between the number of sick days and the proportion of patients feeling understood by colleagues and friends. We found that feeling understood by colleagues and friends decreases with a growing number of sick days. However, when sick days accrue further, this proportion increases again. The number of sick days correlates similarly with both colleagues’ and friends’ understanding. The number of cluster headache patients feeling understood by others decreases with an increasing number of sick days. Their social circles’ frustration with the patients’ failure to meet obligations and expectations are a likely reason. With a growing number of sick days, however, the portion of patients feeling understood rises again despite patients meeting others’ expectations even less. This ‘comprehension paradox’ implies the influence of other factors. We suspect that growing numbers of sick days foster understanding as the disability of the disease becomes increasingly apparent.

Headache Worsening after COVID-19 Vaccination: An Online Questionnaire-Based Study on 841 Patients with Migraine

Vaccines have represented the breakthrough in the fight against COVID-19. Based on reported headache attacks after vaccination in randomized controlled trials, we focused on the effects of COVID-19 vaccine administration on the migraine population, using an online questionnaire published on Italian Facebook groups oriented to headache patients. We collected data about the demographics and clinical parameters of migraine severity, COVID-19 infection, vaccination, and characteristics of headaches following vaccination. Out of 841 migraine patients filling in the questionnaire, 66.47% and 60.15% patients experienced a headache attack (from 1 hour to 7 days) after the first and the second vaccine dose, respectively. The main finding concerns headaches perceived by 57.60% of patients: attacks following vaccination were referred to as more severe (50.62% of patients), long-lasting (52.80% of patients) and hardwearing (49.69% of patients) compared to the usually experienced migraine attacks. This could be related to the production of inflammatory mediators such as type Iβ interferon. Considering the high prevalence of migraine in the general population, awareness of the possibility of headaches worsening following COVID-19 vaccination in these patients may allow both patients and clinicians to face this clinical entity with conscious serenity, and to reduce the waste of resources towards inappropriate health-care.

One-Year Remission Rate of Chronic Headache Comparing Video and Face-to-Face Consultations by Neurologist: Randomized Controlled Trial

Background Chronic headache causing severe headache-related disability for those affected by the disease is under- or misdiagnosed in many cases and therefore requires easy access to a specialist for optimal health care management. Objective The goal of the research is to determine whether video consultations are noninferior to face-to-face consultations in treating chronic headache patients referred to a specialist in Northern Norway. Methods Patients included in the study were recruited from general practice referrals to a specialist at a neurological department in Northern Norway (Tromsø) and diagnosed according to the International Headache Society classification system. In a randomized controlled design, the 1-year remission rate of chronic headache (change from ≥15 to <15 headache days per month during the last 3 months), patient satisfaction with a specialist consultation, and need for follow-up consultations by general practitioners were compared between groups consulted by video and face-to-face in a post hoc analysis. Data were collected by interview (baseline) and questionnaire (follow-up). Results From a baseline cohort of 402 headache patients consecutively referred from general practice to a specialist over 2.5 years, 58.0% (233/402) were classified as chronic headache and included in this study. Response rates were 71.7% (86/120) in the video group and 67.3% (76/113) in the face-to-face group. One-year remission from chronic headache was achieved in 43.0% (37/86) in the video group and 39.5% (30/76) in the face-to-face group (P=.38). Patient satisfaction with consultations were 86.5% (32/37; video) and 93.3% (28/30; face-to-face; P=.25). A total of 30% (11/37) in the video group and 53% (16/30) in the face-to-face group consulted general practitioners during the follow-up period (P=.03), and median number of consultations was 1 (IQR 0-13) and 1.5 (IQR 0-15), respectively (P=.19). Conclusions One-year remission rate from chronic headache was about 40% regardless of consultation form. Likewise, patient satisfaction with consultation and need for follow-up visits in general practice post consultation was similar. Treating chronic headache patients by using video consultations is not inferior to face-to-face consultations and may be used in clinical neurological practice. Trial Registration ClinicalTrials.gov NCT02270177; https://clinicaltrials.gov/ct2/show/NCT02270177

Chronic cluster headache: A study of the telencephalic and cerebellar cortical thickness

Purpose Previous studies on brain morphological alterations in chronic cluster headache revealed inconsistent findings. Method The present cross-sectional explorative study determined telencephalic and cerebellar cortex thickness alterations in a relatively wide sample of chronic cluster headache patients (n = 28) comparing them to matched healthy individuals. Results The combination of two highly robust state-of-the-art approaches for thickness estimation (Freesurfer, CERES), strengthened by functional characterization of the identified abnormal regions, revealed four main results: chronic cluster headache patients show 1) cortical thinning in the right middle cingulate cortex, left posterior insula, and anterior cerebellar lobe, regions involved in nociception's sensory and sensory-motor aspects and possibly in autonomic functions; 2) cortical thinning in the left anterior superior temporal sulcus and the left collateral/lingual sulcus, suggesting neuroplastic maladaptation in areas possibly involved in social cognition, which may promote psychiatric comorbidity; 3) abnormal functional connectivity among some of these identified telencephalic areas; 4) the identified telencephalic areas of cortical thinning present robust interaction, as indicated by the functional connectivity results, with the left posterior insula possibly playing a pivotal role. Conclusion The reported results constitute a coherent and robust picture of the chronic cluster headache brain. Our study paves the way for hypothesis-driven studies that might impact our understanding of the pathophysiology of this condition.

Immunological findings in patients with migraine and other primary headaches: a narrative review

Experimental findings suggest an involvement of neuroinflammatory mechanisms in the pathophysiology of migraine. Specifically, preclinical models of migraine have emphasized the role of neuroinflammation following the activation of the trigeminal pathway at several peripheral and central sites including dural vessels, the trigeminal ganglion and the trigeminal nucleus caudalis. The evidence of an induction of inflammatory events in migraine pathophysiological mechanisms has prompted researchers to investigate the Human leukocyte antigen (HLA) phenotypes as well as cytokine genetic polymorphisms in order to verify their potential relationship with migraine risk and severity. Furthermore, the role of neuroinflammation in migraine seems to be supported by evidence of an increase in pro-inflammatory cytokines, both ictally and interictally, together with the prevalence of Th1 lymphocytes and a reduction in regulatory lymphocyte subsets in peripheral blood of migraineurs. Cytokine profiles of cluster headache patients and those of tension-type headache patients further suggest an immunological dysregulation in the pathophysiology of these primary headaches, although evidence is weaker than for migraine. The present review summarizes available findings to date from genetic and biomarker studies that have explored the role of inflammation in primary headaches.

Great occipital nerve long-acting steroid injections in cluster headache therapy: an observational prospective study

Background Injections targeting the occipital nerve are used to reduce headache attacks and abort cluster bouts in cluster headache patients. There is no widely accepted agreement over the optimal technique of injection, type and doses of steroids and/or anesthetics to use, as well as injection regimens. The aim of this study was to verify the effectiveness and safety of greater occipital nerve long-acting steroid injections in the management of episodic and chronic cluster headache. Methods We conducted a prospective observational cohort study on episodic (ECH) and chronic cluster headache patients (CCH). ECH were included in the study at the beginning of a cluster period. Three injections with 60 mg methylprednisolone were performed on alternate days. We registered the frequency and intensity of attacks three days before and 3, 7 and 30 days after the treatment, the latency of cluster relapse, adverse events, scores evaluating anxiety (Zung scale), depression (Beck’s Depression Scale) and quality of life (Disability Assessment Schedule II, 12-Item Self-Administered Version). Primary outcome was the interruption of the cluster after the three injections. Responders conducted a follow-up period of 12 months. Results We enrolled 60 patients, 47 with ECH and 13 with CCH. We observed a complete response in 47.8% (22/46) of episodic and 33.3% (4/12) of chronic patients. Moreover, a partial response (reduction of at least 50% of attacks) was obtained in further 10.8% (5/46) of episodic and in 33.3% (4/12) of chronic patients at 1 month. Median pain-free period was of 3 months for CCH responders. Only mild adverse events were reported in 38.3% (23/58) cases. Conclusions We suggest three greater occipital nerve injections of 60 mg methylprednisolone on alternate days as useful therapy in episodic and chronic cluster headache. This leads to a long pain-free period in chronic forms. Adverse effects are mild and support its use as first choice. Trial registration The study was inserted in AIFA observational studies register.

PACAP38- and VIP-induced cluster headache attacks are not associated with changes of plasma CGRP or markers of mast cell activation

Background Pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) and vasoactive intestinal polypeptide can provoke cluster headache attacks in up to half of cluster headache patients in their active phase. At present, it is unknown whether provoked attacks are mediated via calcitonin gene-related peptide or mast cell activation. Methods All enrolled patients with cluster headache were randomly allocated to receive a continuous infusion of either PACAP38 (10 pmol/kg/min) or vasoactive intestinal polypeptide (8 pmol/kg/min) over 20 min. We collected clinical data and measured plasma levels of calcitonin gene-related peptide and markers of mast cell activation (tryptase and histamine) at fixed time points: at baseline (T0), at the end of the infusion (T20), 10 min after the infusion (T30), and 70 min after the infusion (T90). Results Blood was collected from episodic cluster headache patients in active phase (n = 14), episodic cluster headache patients in remission (n = 15), and chronic cluster headache patients (n = 15). At baseline, plasma levels of calcitonin gene-related peptide, tryptase, and histamine were not different among the three study groups. Plasma levels of calcitonin gene-related peptide ( p = 0.7074), tryptase ( p = 0.6673), or histamine ( p = 0.4792) remained unchanged during provoked attacks compared to attack-free patients. Conclusion Cluster headache attacks provoked by either PACAP38 or vasoactive intestinal polypeptide were not accompanied by alterations of plasma calcitonin gene-related peptide, tryptase or histamine. The provoked attacks may not be mediated by calcitonin gene-related peptide or mast cell activation. Trial Registration: The study is registered at ClinicalTrials.gov (NCT03814226).

The management and clinical knowledge of headache disorders among general practitioners in Norway: a questionnaire survey

Background General practitioners (GPs) diagnose and manage a majority of headache patients seeking health care. With the aim to understand the potential for clinical improvement and educational needs, we performed a study to investigate Norwegian GPs knowledge about headache and its clinical management. Methods We invited GPs from a random sample of 130 Norwegian continuous medical education (CME) groups to respond to an anonymous questionnaire survey. Results 367 GPs responded to the survey (73% of invited CME groups, 7.6% of all GPs in Norway). Mean age was 46 (SD 11) years, with an average of 18 (SD 10) years of clinical experience. In general the national treatment recommendations were followed, while the International Classification of Headache Disorders and other international guidelines were rarely used. Overall, 80% (n = 292) of the GPs suggested adequate prophylactic medication for frequent episodic migraine, while 28% (n = 101) suggested adequate prophylactic medication for chronic tension-type headache (CTTH). Half (52%, n = 191)) of the respondents were aware that different types of acute headache medication can lead to medication-overuse headache (MOH), and 59% (n = 217) knew that prophylactic headache medication does not lead to MOH. GPs often used MRI in the diagnostic work-up. GPs reported that lack of good treatment options was a main barrier to more optimized treatment of headache patients. Conclusion The knowledge of management of CTTH and MOH was moderate compared to migraine among Norwegian GPs.