Pathophysiology Of Headache Research Articles

The relation of cluster headache to alexithymia, depression, and anxiety.

The pathophysiology of cluster headaches (CHs) involves the trigeminovascular system, the parasympathetic nervous system, and the hypothalamus. Because of the affected hypothalamus, there may be limbic system involvement in CH. To investigate the relationship between depression, anxiety, and alexithymia in CH, to demonstrate that the limbic system is affected. A total of 18 patients with CHs who were outside of cluster period and 18 healthy controls were included. Participants were administered the Beck depression inventory (BDI), Beck anxiety inventory (BAI), and Toronto alexithymia scale-20 (TAS-20). Patients with CHs had significantly higher rates of alexithymia (p = 0.003) and depression (p = 0.014) than controls. There was no significant difference in anxiety levels (p = 0.297) between groups. It was shown that, in addition to previously identified psychiatric disorders, alexithymia can accompany CHs in patients.

Dairy and Headaches: What is the Connection?

Headaches represent a prevalent and burdensome health condition, affecting individuals of all ages worldwide. While dietary factors have been implicated in headache pathophysiology, the association between dairy consumption and headaches remains controversial and inadequately understood. This comprehensive review systematically examines the existing literature to elucidate the relationship between dairy intake and headaches, addressing methodological challenges, potential biases, and gaps in the current knowledge. A thorough search of electronic databases identified relevant observational studies, clinical trials, and mechanistic investigations exploring the impact of dairy consumption on headache incidence, frequency, severity, and duration. Methodological considerations, including study design, measurement of exposure and outcome variables, confounding factors, and sources of bias, were critically evaluated to assess the strength of evidence and validity of findings. Despite heterogeneity across studies, emerging evidence suggests a complex and multifaceted relationship between dairy intake and headaches, influenced by individual characteristics, dietary patterns, headache subtype, and study context. While some studies report a positive association between dairy consumption and headaches, others indicate no significant effect or potential therapeutic benefits of dairy restriction. Mechanistic insights suggest plausible biological mechanisms, including neuroinflammatory pathways, neurotransmitter modulation, vascular effects, and gut-brain interactions, which may mediate the observed associations. Future research directions encompass longitudinal studies, mechanistic investigations, stratified analyses, randomized controlled trials, and exploration of the gut microbiota to further elucidate the underlying mechanisms and inform evidence-based dietary recommendations for headache management. This integrative review underscores the importance of interdisciplinary collaboration and personalized approaches to address the complex interplay between diet, headaches, and overall health.

Harlequin syndrome in a patient with probable hemicrania continua and exertional headache – is there a link? a case report

BackgroundThe harlequin syndrome is a rare disorder of the autonomic nervous system characterized by unilateral diminished flushing and sweating of the face following exposure to heat or physical activity. It results from sympathetic dysfunction and most commonly occurs idiopathically. A secondary development due to an underlying pathology (e.g., carotid artery dissection, tumors) must be excluded at first appearance. There is evidence that the cranial autonomic system is involved in the pathophysiology of trigeminal autonomic headaches like hemicrania continua. Therefore, an overlap in the pathophysiology of harlequin syndrome and trigeminal autonomic headache disorders seems plausible. However, the association of a harlequin syndrome with hemicrania continua was never reported.Case presentationThis work describes the case of a 42‐year‐old female patient presenting to our headache unit. The patient reported persisting unilateral headache of the right side of dragging or squeezing character accompanied by trigeminal autonomic symptoms, including lacrimation, nasal congestion, conjunctival injection and Horner’s syndrome, and was responsive to treatment with 75mg/d indomethacin. Five months after the initial consultation, the patient noted that the upper right quadrant of her face was pale after jogging. A harlequin syndrome was diagnosed. Further, she developed a short-lasting, bilateral headache of pulsatile character during strenuous exercise consistent with exertional headache. Comprehensive diagnostic evaluations, encompassing cranial and cervical MRI scans, laboratory tests, and biopsies, culminated in the diagnosis of Sjögren’s syndrome. This finding suggests that the trigemino-autonomic dysfunction may either be idiopathic or a direct manifestation of Sjögren’s syndrome.ConclusionsThis report documents the case of a rare combination of a headache resembling probable hemicrania continua and the harlequin syndrome (and even exertional headache). It illustrates the underlying anatomy of the autonomic nervous system in a clinical context and emphasizes the hypothesis of a pathophysiological link between abnormal sympathetic activity and trigeminal autonomic headaches.

Monoclonal antibody therapy for refractory chronic migraine-like headache related Lyme disease: a case report

IntroductionLyme disease, caused by Borrelia burgdorferi, can lead to diverse neurological manifestations, including headache. While most Lyme-associated headaches resolve with antibiotics, some may evolve into a refractory chronic migraine-like syndrome. We present a case of post-Lyme chronic migraine-like headache responsive to galcanezumab, a calcitonin gene-related peptide (CGRP) monoclonal antibody.Case ReportA 42-year-old woman developed chronic migraine-like headaches following treatment for Lyme neuroborreliosis. The headaches were refractory to standard preventive therapies and only partially responsive to onabotulinumtoxinA. Administration of galcanezumab resulted in significant reduction of headache frequency, intensity, and impact on daily activities.CommentThis case highlights the potential of CGRP-targeted therapies for persistent migraine-like headaches following Lyme neuroborreliosis. The favorable response to galcanezumab suggests a role for CGRP in the pathophysiology of post-Lyme headache. While further research is needed to establish efficacy and safety, clinicians should consider CGRP monoclonal antibodies for chronic migraine-like headaches refractory to standard treatments in the post-infectious phase of Lyme disease. The emergence of chronic migraine-like headaches following Lyme neuroborreliosis and the response to a CGRP monoclonal antibody in this case underscore the importance of considering targeted migraine therapies in the management of persistent headaches after antibiotic treatment. This report contributes to the understanding of Lyme disease sequelae and potential treatment options, warranting further investigation into the utility of CGRP-targeted therapies in this context.

Circadian functional changes of pain-processing brainstem nuclei and implications for cluster headache: A 7 Tesla imaging study.

Pain thresholds and primary headaches, including cluster headache attacks, have circadian rhythmicity. Thus, they might share a common neuronal mechanism. This study aimed to elucidate how the modulation of nociceptive input in the brainstem changes from noon to midnight. Insights into the mechanism of these fluctuations could allow for new hypotheses about the pathophysiology of cluster headache. This repeated measure observational study was conducted at the University Hospital Zurich from December 2019 to November 2022. Healthy adults between 18 and 85 years of age were eligible. All participants were examined at noon and midnight. We tested the pain threshold on both sides of the foreheads with quantitative sensory testing, assessed tiredness levels, and obtained high-field (7 Tesla) and high-resolution functional magnetic resonance imaging (MRI) at each visit. Functional connectivity was assessed at the two visits by performing a region-of-interest analysis. We defined nuclei in the brainstem implicated in processing nociceptive input as well as the thalamus and suprachiasmatic nucleus as the region-of-interest. Ten people were enrolled, and seven participants were included. First, we did not find statistically significant differences between noon and midnight of A-delta-mediated pain thresholds (median mechanical pain threshold at noon: left 9.2, right 9.2; at night: left 6.5, right 6.1). Second, after correction for a false discovery rate, we found changes in the mechanical pain sensitivity to have a statistically significant effect on changes in the functional connectivity between the left parabrachial nucleus and the suprachiasmatic nucleus (T = -40.79). The MRI data analysis suggested that brain stem nuclei and the hypothalamus modulate A-delta-mediated pain perception; however, these changes in pain perception did not lead to statistically significantly differing pain thresholds between noon and midnight. Hence, our findings shed doubt on our hypothesis that the physiologic circadian rhythmicity of pain thresholds could drive the circadian rhythmicity of cluster headache attacks.

Plasma calcitonin gene-related peptide levels in idiopathic intracranial hypertension: an exploratory study

BackgroundIdiopathic intracranial hypertension (IIH) is a debilitating condition characterized by increased intracranial pressure often presenting with chronic migraine-like headache. Calcitonin gene-related peptide (CGRP) plays an important pathophysiological role in primary headaches such as migraine, whilst its role in IIH has not yet been established.MethodsThis longitudinal exploratory study included patients with IIH, episodic migraine (EM) in a headache-free interval and healthy controls (HC). Blood samples were collected from a cubital vein and plasma CGRP (pCGRP) levels were measured by standardized ELISA.ResultsA total of 26 patients with IIH (mean age 33.2 years [SD 9.2], 88.5% female, median BMI 34.8 kg/m2 [IQR 30.0–41.4]), 30 patients with EM (mean age 27.6 years [7.5], 66.7% female) and 57 HC (mean age 25.3 years [5.2], 56.1% female) were included. pCGRP levels displayed a wide variation in IIH as well as in EM and HC on a group-level. Within IIH, those with migraine-like headache had significantly higher pCGRP levels than those with non-migraine-like headache (F(2,524) = 84.79; p < 0.001) and headache absence (F(2,524) = 84.79; p < 0.001) throughout the observation period, explaining 14.7% of the variance in pCGRP levels. CGRP measurements showed strong intraindividual agreement in IIH (ICC 0.993, 95% CI 0.987–0.996, p < 0.001). No association was found between pCGRP levels and ophthalmological parameters.ConclusionsAlthough interindividual heterogeneity of pCGRP levels is generally high, migraine-like headache seems to be associated with higher pCGRP levels. CGRP may play a role in the headache pathophysiology at least in a subgroup of IIH.

MERTK in the rat trigeminal system: a potential novel target for cluster headache?

The trigeminal system is key to the pathophysiology of migraine and cluster headache, two primary headache disorders that share many features. Recently, MER proto-oncogene tyrosine kinase (MERTK), a cell surface receptor, was strongly associated with cluster headache through genetic studies. Further, the MERTK ligand galectin-3 has been found to be elevated in serum of migraine patients. In this study, MERTK and MERTK ligands were investigated in key tissue to better understand their potential implication in the pathophysiology of primary headache disorders. Immunohistochemistry was used to map MERTK and galectin-3 expression in rat trigeminal ganglia. RT-qPCR was used to assess MERTK gene expression in blood, and ELISA immunoassays were used for MERTK ligand quantification in serum from study participants with and without cluster headache. MERTK gene expression was elevated in blood samples from study participants with cluster headache compared to controls. In addition, MERTK ligand galectin-3 was found at increased concentration in the serum of study participants with cluster headache, whereas the levels of MERTK ligands growth arrest specific 6 and protein S unaffected. MERTK and galectin-3 were both expressed in rat trigeminal ganglia. Galectin-3 was primarily localized in smaller neurons and to a lesser extent in C-fibres, while MERTK was found in satellite glia cells and in the outer membrane of Schwann cells. Interestingly, a strong MERTK signal was found specifically in the region proximal to the nodes of Ranvier. The overexpression of MERTK and galectin-3 in tissue from study participants with cluster headache, as well as the presence of MERTK in rat peripheral satellite glia cells and Schwann cells in the trigeminal ganglia, further highlights MERTK signalling as an interesting potential future therapeutic target in primary headache.Graphical

Influence of Human Leukocyte Antigen in Susceptibility to Migraine in Patients

Migraine affects more than one billion individuals each year across the world, and is one of the most common neurologic disorders, with a high prevalence and morbidity, especially among young adults and females. Migraine is associated with a wide range of comorbidities, which range from stress and sleep disturbances to suicide. The complex and largely unclear mechanisms of migraine development have resulted in the proposal of various social and biological risk factors, such as hormonal imbalances, genetic and epigenetic influences, as well as cardiovascular, neurological, and autoimmune diseases. 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 (CH) 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.

Can Long-Term Outcomes of Posttraumatic Headache be Predicted?

Headache is one of the most common symptoms of traumatic brain injury, and it is more common in patients with mild, rather than moderate or severe, traumatic brain injury. Posttraumatic headache can be the most persistent symptom of traumatic brain injury. In this article, we review the current understanding of posttraumatic headache, summarize the current knowledge of its pathophysiology and treatment, and review the research regarding predictors of long-term outcomes. To date, posttraumatic headache has been treated based on the semiology of the primary headache disorder that it most resembles, but the pathophysiology is likely to be different, and the long-term prognosis differs as well. No models exist to predict long-term outcomes, and few studies have highlighted risk factors for the development of acute and persistent posttraumatic headaches. Further research is needed to elucidate the pathophysiology and identify specific treatments for posttraumatic headache to be able to predict long-term outcomes. In addition, the effect of managing comorbid traumatic brain injury symptoms on posttraumatic headache management should be further studied. Posttraumatic headache can be a persistent symptom of traumatic brain injury, especially mild traumatic brain injury. It has traditionally been treated based on the semiology of the primary headache disorder it most closely resembles, but further research is needed to elucidate the pathophysiology of posttraumatic headache and determine risk factors to better predict long-term outcomes.

Update on Cluster Headaches: From Genetic to Novel Therapeutic Approaches

Cluster headaches affect 0.1% of the population and are four times more common in males than in females. Patients with this condition present with severe unilateral head pain localized in the frontotemporal lobe, accompanied by ipsilateral lacrimation, conjunctival injection, nasal congestion, diaphoresis, miosis, and eyelid edema. Recently, the first genome-wide association study of cluster headaches was conducted with the goal of aggregating data for meta-analyses, identifying genetic risk variants, and gaining biological insights. Although little is known about the pathophysiology of cluster headaches, the trigeminovascular and trigeminal autonomic reflexes and hypothalamic pathways are involved. Among anti-calcitonin gene-related peptide monoclonal antibodies, galcanezumab has been reported to be effective in preventing episodic cluster headaches.

Compensated Hypogonadism Identified in Males with Cluster Headache: A Prospective Case-Controlled Study.

Androgens have been hypothesized to be involved in the pathophysiology of cluster headache due to the male predominance, but whether androgens are altered in patients with cluster headache remains unclear. We performed a prospective, case-controlled study in adult males with cluster headache. Sera were measured for hormones including testosterone, luteinizing hormone (LH), and sex hormone-binding globulin in 60 participants with episodic cluster headache (during a bout and in remission), 60 participants with chronic cluster headache, and 60 age- and sex-matched healthy controls. Free testosterone (fT) was calculated according to the Vermeulen equation. Shared genetic risk variants were assessed between cluster headache and testosterone concentrations. The mean fT/LH ratio was reduced by 35% (95% confidence interval [CI]: 21%-47%, p < 0.0001) in patients with chronic cluster headache and by 24% (95% CI: 9%-37%, p = 0.004) in patients with episodic cluster headache compared to controls after adjusting for age, sleep duration, and use of acute medication. Androgen concentrations did not differ between bouts and remissions. Furthermore, a shared genetic risk allele, rs112572874 (located in the intron of the microtubule associated protein tau (MAPT) gene on chromosome 17), between fT and cluster headache was identified. Our results demonstrate that the male endocrine system is altered in patients with cluster headache to a state of compensated hypogonadism, and this is not an epiphenomenon associated with sleep or the use of acute medication. Together with the identified shared genetic risk allele, this may suggest a pathophysiological link between cluster headache and fT. ANN NEUROL 2024;95:1149-1161.

Is painful temporomandibular disorder a real headache for many patients?

Temporomandibular disorders (TMDs) and primary headaches are common pain conditions and often co-exist. TMD classification includes the term ‘headache secondary to TMD' but this term does not acknowledge the likelihood that primary headache pathophysiology underpins headache causing painful TMD signs and symptoms in many patients. The two disorders have a complex link and we do not fully understand their interrelationship. However, growing evidence shows a significant association between the two disorders. This article reviews the possible connection between temporomandibular disorders and primary headaches, specifically migraine, both anatomically and pathogenetically.

Guidelines of the International Headache Society for controlled trials of pharmacological preventive treatment for persistent post-traumatic headache attributed to mild traumatic brain injury.

Persistent headache attributed to traumatic injury to the head is divided into two subtypes, one attributed to moderate or severe traumatic injury and another attributed to mild traumatic injury (i.e., concussion). The latter is much more prevalent, in part because more than 90% of cases with traumatic brain injury are classified as mild. The pathophysiology of persistent post-traumatic headache is poorly understood and the underlying mechanisms are likely multifactorial. There is currently no approved treatment specifically for persistent post-traumatic headache, and management strategies rely on medications used for migraine or tension-type headache. Therefore, high-quality trials are urgently needed to support clinical decision-making and optimize management strategies. International guidelines can facilitate appropriate trial design and ensure the acquisition of high-quality data evaluating the efficacy, tolerability, and safety of available and novel pharmacological therapies for the preventive treatment of persistent post-traumatic headache. The development of this guideline was based on a literature review of available studies in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials, along with a review of previously published guidelines for controlled trials of preventive treatment for episodic and chronic migraine. The identified literature was critically appraised, and due to the scarcity of scientific evidence, recommendations were primarily based on the consensus of experts in the field. To provide guidelines for designing state-of-the-art controlled clinical trials aimed at evaluating the effectiveness of preventive treatments for persistent post-traumatic headache attributed to mild traumatic brain injury.

Factors associated to the presence of headache in patients with influenza infection and its consequences: a 2010–2020 surveillance-based study

Headache is a common symptom of influenza infection; however, its causes and consequences remain uncertain. In this manuscript, we analyzed which demographic and clinical factors were associated with the presence of headache during the course of influenza infection and whether patients with headache had a different prognosis, evaluated by need of hospitalization, sick leave or school absenteeism. The influence study (NCT05704335) was an observational study that analyzed data routinely collected from the Health Sentinel Network between 2010 and 2020. During the study period, 7832 cases were considered, among which, 5275 (67.4%) reported headache. The presence of headache was independently associated with myalgia (2.753; 95%CI: 2.456–3.087, P < 0.001), asthenia (OR: 1.958; 95%CI: 1.732–2.214, P < 0.001), shivering (OR: 1.925; 95%CI: 1.718–2.156, P < 0.001), nasopharyngeal erythema (OR: 1.505; 95%CI: 1.293–1.753, P < 0.001), fever (OR: 1.469; 95%CI: 1.159–1.861; P = 0.001), sudden onset of symptoms (OR: 1.380; 95%CI: 1.120–1.702, p = 0.004), female sex (OR: 1.134; 95%CI: 1.023–1.257, P = 0.018), and gastrointestinal symptoms (OR: 1.169; 95%CI: 1.039–1.315; P = 0.01). Patients with headache had a sex and age adjusted lower odds of being referred to the hospital (OR: 0.463; 95%CI: 0.264–0.812, P = 0.007) and a higher odd of having a sick leave and/or school absenteeism (absenteeism (OR: 1.342; 95%CI: 1.190–1.514, P < 0.001). In conclusion, the presence of headache seems associated with symptoms caused by the innate immune response. These findings support a headache pathophysiology linked with the innate immune response. Due to the potential negative consequences and its treatable nature, clinicians should systematically evaluate it and, whenever necessary, treat it too.

Pathophysiology of cluster headache: From the trigeminovascular system to the cerebral networks.

Despite advances in neuroimaging and electrophysiology, cluster headache's pathogenesis remains unclear. This review will examine clinical neurophysiology studies, including electrophysiological and functional neuroimaging, to determine if they might help us construct a neurophysiological model of cluster headache. Clinical, biochemical, and electrophysiological research have implicated the trigeminal-parasympathetic system in cluster headache pain generation, although the order in which these two systems are activated, which may be somewhat independent, is unknown. Electrophysiology and neuroimaging have found one or more central factors that may cause seasonal and circadian attacks. The well-known posterior hypothalamus, with its primary circadian pacemaker suprachiasmatic nucleus, the brainstem monoaminergic systems, the midbrain, with an emphasis on the dopaminergic system, especially when cluster headache is chronic, and the descending pain control systems appear to be involved. Functional connection investigations have verified electrophysiological evidence of functional changes in distant brain regions connecting to wide cerebral networks other than pain. We propose that under the impact of external time, an inherited misalignment between the primary circadian pacemaker suprachiasmatic nucleus and other secondary extra- suprachiasmatic nucleus clocks may promote disturbance of the body's internal physiological clock, lowering the threshold for bout recurrence.

Involvement of the ipsilateral-to-the-pain anterior–superior hypothalamic subunit in chronic cluster headache

BackgroundDespite hypothalamus has long being considered to be involved in the pathophysiology of cluster headache, the inconsistencies of previous neuroimaging studies and a limited understanding of the hypothalamic areas involved, impede a comprehensive interpretation of its involvement in this condition.MethodsWe used an automated algorithm to extract hypothalamic subunit volumes from 105 cluster headache patients (57 chronic and 48 episodic) and 59 healthy individuals; after correcting the measures for the respective intracranial volumes, we performed the relevant comparisons employing logist regression models.Only for subunits that emerged as abnormal, we calculated their correlation with the years of illness and the number of headache attacks per day, and the effects of lithium treatment. As a post-hoc approach, using the 7 T resting-state fMRI dataset from the Human Connectome Project, we investigated whether the observed abnormal subunit, comprising the paraventricular nucleus and preoptic area, shows robust functional connectivity with the mesocorticolimbic system, which is known to be modulated by oxytocin neurons in the paraventricular nucleus and that is is abnormal in chronic cluster headache patients.ResultsPatients with chronic (but not episodic) cluster headache, compared to control participants, present an increased volume of the anterior–superior hypothalamic subunit ipsilateral to the pain, which, remarkably, also correlates significantly with the number of daily attacks. The post-hoc approach showed that this hypothalamic area presents robust functional connectivity with the mesocorticolimbic system under physiological conditions. No evidence of the effects of lithium treatment on this abnormal subunit was found.ConclusionsWe identified the ipsilateral-to-the-pain antero-superior subunit, where the paraventricular nucleus and preoptic area are located, as the key hypothalamic region of the pathophysiology of chronic cluster headache. The significant correlation between the volume of this area and the number of daily attacks crucially reinforces this interpretation. The well-known roles of the paraventricular nucleus in coordinating autonomic and neuroendocrine flow in stress adaptation and modulation of trigeminovascular mechanisms offer important insights into the understanding of the pathophysiology of cluster headache.

Altered metabolites in the periaqueductal gray of COVID-19 patients experiencing headaches: a longitudinal MRS study.

Headache is one of the most common symptoms of acute COVID-19 infection. However, its mechanisms remain poorly understood, and there is a lack of studies investigating changes in the periaqueductal gray (PAG) in COVID-19 patients exhibiting headaches. The study aimed to explore the alterations in metabolites of the PAG pre- and post-COVID-19 infection in individuals who suffered from headaches during the acute phase of the disease using proton magnetic resonance spectroscopy (1H-MRS). Fifteen participants who experienced headaches during the acute phase of COVID-19 were recruited. All subjects underwent two proton magnetic resonance spectroscopy (1H-MRS) examinations focusing on the PAG before and after they were infected. Metabolite changes were assessed between the pre- and post-infection groups. The combined glutamine and glutamate/total creatine ratio (Glx/tCr) was increased in the PAG following COVID-19 infection. The total choline/total creatine ratio (tCho/tCr) in the pre-infection group was negatively correlated with the duration of headache during the COVID-19 acute phase. The present study indicates that PAG plays a pivotal role in COVID-19 headaches, thereby supporting the involvement of trigeminovascular system activation in the pathophysiology of COVID-19 headaches.

The genetics and chronobiology of cluster headache.

Cluster headache displays uniquely rhythmic patterns in its attack manifestation. This strong chronobiological influence suggests that part of the pathophysiology of cluster headache is distinctly different from migraine and has prompted genetic investigations probing these systems. This is a narrative overview of the cluster headache chronobiological phenotype from the point of view of genetics covering existing knowledge, highlighting the specific challenges in cluster headache and suggesting novel research approaches to overcome these. The chronobiological features of cluster headache are a hallmark of the disorder and while discrepancies between study results do exist, the main findings are highly reproducible across populations and time. Particular findings in subgroups indicate that the heritability of the disorder is linked to chronobiological systems. Meanwhile, genetic markers of circadian rhythm genes have been implicated in cluster headache, but with conflicting results. However, in two recently published genome wide association studies two of the identified four loci include genes with an involvement in circadian rhythm, MER proto-oncogene, tyrosine kinase and four and a half LIM domains 5. These findings strengthen the involvement of circadian rhythm in cluster headache pathophysiology. Studying chronobiology and genetics in cluster headache presents challenges unique to the disorder. Researchers are overcoming these challenges by pooling various data from different cohorts and performing meta-analyses providing novel insights into a classically enigmatic disorder. Further progress can likely be made by combining deep pheno- and genotyping.

Post spinal puncture headache: diagnosis, risk factors and treatment

Spinal anesthesia is one of the most used anesthetic techniques, having been in existence for over 100 years, and over time it has been improved by the development of a new needle design, gauge, tip shapes, as well as more precise indications and contraindications. However, even so, there are still possible complications due to this procedure, especially headache after puncture of the dura mater, and, because of that, this procedure carries with it a great increase of taboos and prejudices. Although it is clear that reducing the size of the dural perforation reduces CSF loss, thus making the incidence of headache less likely, there are many other issues to be clarified regarding the pathophysiology, treatment and prevention of post-dural puncture headache. How does needle design, size, and orientation influence CSF leakage through dural perforation? Can pharmacological methods reduce symptoms of post-dural puncture headache? Can epidural blood patch help in the treatment of post-spinal anesthesia headache? Can epidural blood patch act prophylactically? Does epidural saline solution reduce the rate of CSF loss? Thus, this article aims to answer these questions according to the most recent studies and make an objective review of post spinal anesthesia headache with an approach to pathophysiology, diagnosis, clinical scenario, risk factors, prevention and therapeutic options.

Optic nerve sheath diameter measurement for prediction of postdural puncture headache.

Intracranial hypotension due to cerebrospinal fluid leak is mainly the causal factor for the pathophysiology of postdural puncture headache (PDPH). In this study, we aimed to evaluate the effectiveness of optic nerve sheath diameter (ONSD) measurement in predicting the development of PDPH in patients undergoing spinal anesthesia. According to the American Society of Anesthesiology (ASA) physical classification I-III, 83 patients aged 18-65 years scheduled for spinal anesthesia for elective surgery were included in the study. Demographic data (age, ASA, sex, smoking, migraine, and PDPH history) and operative data were recorded. Preoperative ONSD measurements were taken in the right and left eye, axial, and sagittal planes. The mean of four measurements was recorded before and 24h after the spinal anesthesia. A total of 83 patients (59 males and 24 females) were included in the study. In our study, the rate of PDPH development was determined as 22.9% (n = 19). There was a statistically significant difference in the preoperative and postoperative ONSD values between patients with and without PDPH development (p = 0.046). In the receiver operating characteristic analysis, the area under the curve was 0.843, and the cutoff value was 0.4. The difference between the ONSD values measured before and after spinal anesthesia may be an important parameter for predicting the risk of PDPH development.