Paroxysmal Hemicrania Research Articles

Indomethacin-responsive refractory headache: Two case reports in children after hemispherectomy for Rasmussen's encephalitis.

Indomethacin-responsive headaches occur in youth and include primary headache syndromes such as hemicrania continua and paroxysmal hemicrania. Both are trigeminal autonomic cephalalgias (TACs). In pediatrics TACs are rare. Moreover, they may differ in their phenotypes and response to indomethacin compared to adults. Secondary causes for side-locked headaches can have vascular, neoplastic, and inflammatory etiologies, emphasizing the importance of imaging in the evaluation of these headache types. Post-craniotomy indomethacin-responsive headaches have been described in adults, but not in children. Written consent was obtained from the patients' families and written assent from the two children for publication. We report the course of two children, both with a history of Rasmussen's encephalitis treated with functional hemispherectomies, who subsequently developed debilitating, side-locked, medically refractory headaches several months after surgery. Headaches were on the same side of their encephalitis and surgery. In both instances, the headaches were exquisitely and rapidly responsive to indomethacin. Headache freedom was maintained on low doses of indomethacin (0.14-0.5 mg/kg/day). In cases of refractory side-locked headaches following a craniotomy or neuroinflammatory condition in children, one may consider indomethacin as a treatment option after evaluation for other secondary etiologies.

How can you manage an indomethacin-responsive headache in someone who cannot take indomethacin?

Paroxysmal hemicrania and hemicrania continua are rare primary headache disorders which are distinguished by an absolute response to indomethacin. As a matter of importance, no guidelines have been proposed for alternative therapeutic options in case of indomethacin intolerance. The purpose of this review is to provide an update on the current findings, especially focusing on the past 18 months, in the treatment of both paroxysmal hemicrania and hemicrania continua and to provide proposed management recommendations based on summarized evidence. Apart from well recognized gastrolesive effects of indomethacin, a substantial number of patients may suffer from neuropsychiatric adverse reactions. Recent studies demonstrated that melatonin, which has been known for its effectiveness for hemicrania continua, is also useful for paroxysmal hemicrania. Promising nonpharmacological treatment option, which is noninvasive vagus nerve stimulation, has been shown to be beneficial for both indomethacin-responsive headache disorders allowing the reduction of indomethacin dosage. Although the data on substitutive medication choice for indomethacin are currently scarce, the most consistent results have been repeatedly achieved with acemethacin, selective COX-2 inhibitors, and anticonvulsants. However, considering the crucial role of pathophysiology, research investigating the efficacy of drugs targeting the trigemino-vascular system activation, as well as controlled trials assessing the efficacy involving the aforementioned therapeutic options are still vague. In spite of numerous reports suggesting reliable alternatives to indomethacin, the consensus on pharmacological therapy guidelines for indomethacin-responsive headache disorders has not yet been reached. Further research and agreement from the experts' standpoint are needed for an establishment of reliable treatment recommendations.

Diaphragmatic small bowel disease in a patient with resistant migraine and medication overuse treated with galcanezumab

Background: Monoclonal antibodies directed against Calcitonin Gene-Related Peptide (CGRP) or its receptor have greatly improved the quality of life of migraine patients. However, these treatments must be administered with caution in patients with constipation or inflammatory bowel disease, considering that non-steroidal anti-inflammatory drugs, widely used by patients with migraine to treat attacks, may have gastrointestinal side effects. Methods: After receiving informed consent, we obtained patient's information from her clinical documentation and archived medical records. Results: We report the case of a patient with a clinical history of migraine with and without aura, paroxysmal hemicrania, and overuse of indomethacin, who received a diagnosis of symptomatic small bowel diaphragmatic disease under prophylactic treatment with galcanezumab. Due to the intestinal implications of CGRP, we decided to discontinue this therapy and begin OnabotulinumtoxinA treatment. Conclusions: This case report recommends extreme caution when starting anti-CGRP mAbs treatment in patients with longstanding medication overuse with NSAIDs and abdominal symptoms.

Sex and gender differences in the epidemiology, clinical features, and pathophysiology of trigeminal autonomic cephalalgias

Emerging evidence suggests that primary headaches, classified as trigeminal autonomic cephalalgias (TACs), may exhibit sex and gender differences in clinical features, mechanisms, and treatment responses. While epidemiological and clinical gender-specific differences have been widely reported for cluster headache, limited evidence is available for other TACs. In this narrative review, we have analyzed the existing data on the influence of sex and gender on cluster headache, paroxysmal hemicrania, short-lasting unilateral neuralgiform headache attacks, and hemicrania continua. Given the role of calcitonin gene-related peptide (CGRP) in migraine and cluster headache, sex and gender differences in the levels and function of CGRP in preclinical models and patients are reported. Future studies are warranted to elucidate the role of sex and gender in the complex interplay of genetic and neurochemical factors in TACs.

Prophylactic Cyproheptadine to Control Paroxysmal Hemicrania Attacks: A Preliminary Investigation.

Paroxysmal hemicrania (PH) is a severe short-lasting headache usually localized around the eye. It might occur in conjunction with ipsilateral autonomic manifestations of trigeminal nerve stimulation. PH responds well to indomethacin treatment; however, considering the adverse effects of indomethacin, its long-term use is a matter of question and investigations about other prophylactic medications are going on, but they are inconclusive. The current study aims to investigate the efficacy of prophylactic use of cyproheptadine to control PH symptoms. The current clinical trial was conducted on 20 children diagnosed with PH undergoing prophylactic treatment with cyproheptadine syrup at a dosage of 0.2-0.4 mg/kg twice daily for a period of 3 months. The duration, frequency, and severity of headaches were assessed at baseline and then monthly for 3 months. Significantly shorter duration, less frequency, and less severity of headaches were observed in the postintervention assessments of the patients (P < 0.001). The effect size analysis showed that the greatest effect of the treatment was on the intensity of the headache (effect size: 0.866) and the least effect was on duration of the headache (effect size: 0.775). Drowsiness (5%) and increased appetite (30%) were the only adverse effects of treatment with cyproheptadine. Findings of this study showed that short-term prophylactic cyproheptadine in divided doses of 0.2-0.4 mg/kg could appropriately improve PH in terms of frequency, duration, and the intensity of the attacks. Nevertheless, further investigations are strongly recommended.

Efficacy and safety of greater occipital nerve block with a small volume of lidocaine and methylprednisolone in tertiary headache center

Background: The greater occipital nerve block (GON-B) is used in clinical practice for treating different forms of headache. There is no standardized procedure to perform GON-B. This study evaluates the efficacy and feasibility of a low-volume GON-B protocol utilizing a pre-mixed solution of lidocaine (10 mg) and methylprednisolone (40 mg) across various headache disorders. Methods: This observational case series included patients receiving their first GON-B from November 2019 to February 2021. Participants were diagnosed with migraine, cluster headache, cervicogenic headache, or paroxysmal hemicrania. The primary outcome was the degree of response to the GON-B. Results: Thirty-nine patients with migraine underwent a first GON-B. Regarding headache frequency, 26% achieved substantial response and 33% partial response. For headache intensity, 26% reported substantial and 49% partial improvement. Migraine patients experienced a significant reduction in median monthly headache days from 25 to 13 (p=0.001) and in headache intensity from a median of 8 to 6 on the Numerical Rating Scale (NRS) scale (p&lt;0.001). Of the 27 patients receiving a second GON-B, 33% had a substantial response, 48% a partial response, and 19% no response. Results from subsequent sessions were consistent with these findings. Ten patients with cluster headache underwent GON-B, showing a significant reduction in pain intensity from a median NRS score of 10 to 5 (p=0.008). Two patients with cervicogenic headache showed a partial response to GON-B, with pain intensity decreasing from 8 to 6 and 8 to 7 over 30 monthly episodes. A patient with paroxysmal hemicrania received seven GON-B injections, reducing daily attacks from 30 to 10 and pain intensity from 7 to 6 on the NRS scale. Conclusions: These outcomes affirm GON-B potential in interrupting pain pathways, even at a low dose, in a wide range of headache disorders.

Indomethacin-Responsive Headache Disorders.

This article describes the clinical features and treatment of the indomethacin-responsive headache disorders paroxysmal hemicrania and hemicrania continua. Both paroxysmal hemicrania and hemicrania continua are treated with indomethacin at the lowest clinically useful dose. It has recently become clear that some patients with either condition may respond to treatment with noninvasive vagus nerve stimulation, which can be both indomethacin sparing and, in some cases, headache controlling. Given the lifelong nature of both paroxysmal hemicrania and hemicrania continua, brain imaging with MRI is recommended when the conditions are identified, specifically including pituitary views. Paroxysmal hemicrania and hemicrania continua are indomethacin-responsive headache disorders that offer a rewarding and unique opportunity to provide marked clinical improvement when recognized and treated appropriately. These disorders share the final common pathway of the trigeminal-autonomic reflex, with head pain and cranial autonomic features, and are differentiated pathophysiologically by the pattern of brain involvement, which can be seen using functional imaging. They have distinct differential diagnoses to which the clinician needs to remain alert.

One-year prevalence of cluster headache, hemicrania continua, paroxysmal hemicrania and SUNCT in Norway: a population-based nationwide registry study

BackgroundThere is lack of population-based studies evaluating the prevalence of paroxysmal hemicrania, hemicrania continua and short-lasting unilateral neuralgiform headache attacks.ObjectivesThe aim of this study was to investigate the gender-specific 1-year prevalence of cluster headache, paroxysmal hemicrania, hemicrania continua, and short-lasting unilateral neuralgiform headache attacks.MethodsA nationwide study was conducted from January 1 2022 and December 31 2022 by linking diagnostic codes from Norwegian Patient Registry and prescription of relevant drugs from Norwegian Prescription Database on an individual basis. The 1-year prevalence with 95% confidence intervals (CI) of cluster headache, paroxysmal hemicrania, hemicrania continua and short-lasting unilateral neuralgiform headache attacks are estimated based on the combination of diagnostic codes, prescription of drugs and corresponding reimbursement codes.ResultsAmong 4,316,747 individuals aged ≥ 18 years, the 1-year prevalence per 100,000 was 14.6 (95% CI 13.5–15.8) for cluster headache, 2.2 (95% CI 1.8–2.7) for hemicrania continua, 1.4 (95% CI 1.0–1.8) for paroxysmal hemicrania, and 1.2 (95% CI 0.8–1.4) for short-lasting unilateral neuralgiform headache attacks. For all the trigeminal autonomic cephalalgies, cluster headache included, the prevalence was higher for women than men.ConclusionsIn this nationwide register-based study, we found a 1-year prevalence per 100,100 of 14.6 for cluster headache, 2.2 for hemicranias continua, 1.4 for paroxysmal hemicranias, and 1.2 for short-lasting unilateral neuralgiform headache attacks. This is the first study reporting higher prevalence of cluster headache for women than men.

Melatonin in hemicrania continua and paroxysmal hemicrania.

Hemicrania continua (HC) and paroxysmal hemicrania (PH) belong to a group of primary headache disorders called trigeminal autonomic cephalalgias. One of the diagnostic criteria for both HC and PH is the absolute response to the therapeutic dose of indomethacin. However, indomethacin is discontinued in many patients as a result of intolerance to its side effects. Melatonin, a pineal hormone, which shares similar chemical structure to indomethacin, has been reported to have some efficacy for HC in previous case reports and series. To our knowledge, there is no literature regarding the use of melatonin in PH. We aimed to describe the clinical use of melatonin in the preventive management of HC and PH. Patient level data were extracted as an audit from routinely collected clinical records in consecutive patients seen in outpatient neurology clinic at King's College Hospital, London, UK, from September 2014 to April 2023. Our cohort of patients were identified through a search using the keywords: hemicrania continua, paroxysmal hemicrania, melatonin and indomethacin. Descriptive statistics including absolute and relative frequencies, mean ± SD, median and interquartile range (IQR) were used. Fifty-six HC patients were included with a mean ± SD age of 52 ± 16 years; 43 of 56 (77%) patients were female. Melatonin was taken by 23 (41%) patients. Of these 23 patients, 19 (83%) stopped indomethacin because of different side effects. The doses of melatonin used ranged from 0.5 mg to 21 mg, with a median dose of 10 mg (IQR = 6-13 mg). Fourteen (61%) patients reported positive relief for headache, whereas the remaining nine (39%) patients reported no headache preventive effect. None of the patients reported that they were completely pain free. Two patients continued indomethacin and melatonin concurrently for better symptom relief. Eight patients continued melatonin as the single preventive treatment. Side effects from melatonin were rare. Twenty-two PH patients were included with mean ± SD age of 50 ± 17 years; 17 of 22 (77%) patients were female. Melatonin was given to six (27%) patients. The median dose of melatonin used was 8 mg (IQR = 6-10 mg). Three (50%) patients responded to melatonin treatment. One of them used melatonin as adjunctive treatment with indomethacin. Melatonin showed some efficacy in the treatment of HC and PH with a well-tolerated side effect profile. It does not have the same absolute responsiveness as indomethacin, at the doses used, although it does offer a well-tolerated option that can have significant ameliorating effects in a substantial cohort of patients.

SUNCT, SUNA and short-lasting unilateral neuralgiform headache attacks: Debates and an update.

Short-lasting unilateral neuralgiform headache attacks (SUNHA) have the features of both short-lasting unilateral neuralgiform pain, such as trigeminal neuralgia or stabbing headache, and associated trigeminal autonomic symptoms, such as paroxysmal hemicrania or cluster headache. Recognizing and adequately treating SUNHA is essential but current treatment methods are ineffective in treating SUNHA. We reviewed the changes in the concept of short-lasting unilateral neuralgiform headache attacks and provide a narrative review of the current medical and surgical treatment options, from the first choice of treatment for patients to treatments for selective intractable cases. Unlike the initial impression of an intractable primary headache disorder affecting older men, SUNHA affects both sexes throughout their lifespan. One striking feature of SUNHA is that the attacks are triggered by cutaneous or intraoral stimulation. The efficacy of conventional treatments is disappointing and challenging, and preventive therapy is the mainstay of treatment because of highly frequent attacks of a very brief duration. Amongst them, lamotrigine is effective in approximately two-third of the patients with SUNHA, and intravenous lidocaine is essential for the management of acute exacerbation of intractable pain. Topiramate, oxcarbazepine and gabapentin are considered good secondary options for SUNHA, and botulinum toxin can be used in selective cases. Neurovascular compression is commonly observed in SUNHA, and surgical approaches, such as neurovascular compression, have been reported to be effective for intractable cases. Recent advances in the understanding of SUNHA have improved the recognition and treatment approaches for this unique condition.

Hemicrania paroxística com representação na face e associação com disfunção temporomandibular: relato de caso

ABSTRACT Paroxysmal Hemicrania is a trigeminal autonomic cephalalgia described as a severe and strictly unilateral pain, which occurs in paroxysms at orbital, supraorbital and/ or temporal region. A 45-year-old woman presented to an orofacial pain specialist reporting severe, burning, throbbing, strictly right-sided headache associated to ipsilateral autonomic symptoms and orofacial pain. The pain was perceived on the maxillary region followed by pain spread to the head. Interdisciplinary evaluation, along with absolute responsiveness to indomethacin and normal Brain Magnetic Resonance imaging, led to the diagnosis of primary Episodic paroxysmal hemicrania with facial representation and myofascial pain of masticatory muscles. Dentists should be aware of paroxysmal hemicrania with facial representation and the possibility of temporomandibular disorder coexistence, in order to avoid misdiagnosis and inadequate management. Paroxysmal hemicrania may be first perceived on the face and may be associated with interparoxysmal pain. In these cases, efficient anamnesis and clinical evaluation followed by interdisciplinary approach is needed.

Epidemiology and clinical features of paroxysmal hemicrania: Asystematic review and meta-analysis.

To assess the prevalence or relative frequency of paroxysmal hemicrania and its clinical features in the adult general population and among adult patients evaluated for headache in tertiary care. Paroxysmal hemicrania is a rare trigeminal autonomic cephalalgia with characteristic attacks of headache, associated cranial autonomic symptoms and signs, and an absolute response to indomethacin. Its epidemiological burden remains unknown in both the adult general population and among adult patients evaluated for headache in a tertiary care setting. Moreover, the frequencies of the clinical features associated with paroxysmal hemicrania have not been well established. A literature search of PubMed and Embase was conducted from January 1, 1988, to January 20, 2023. Eligible for inclusion were observational studies reporting the point prevalence or relative frequency of paroxysmal hemicrania or its clinical features in the adult general population or among adult patients evaluated for headache in tertiary care. Two independent investigators (M.J.H. and J.G.L.) performed the title, abstract, and full-text article screening. Each included study's risk of bias was critically appraised using the Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data. Estimates of prevalence or relative frequency were calculated using a random-effects meta-analysis. The between-study heterogeneity was assessed using the I2 statistic and further explored with meta-regression. This study was pre-registered on PROSPERO (identifier: CRD42023391127). A total of 17 clinic-based studies and one population-based study met the eligibility criteria. Importantly, an overall high risk of bias was observed across the eligible studies. The relative frequency of paroxysmal hemicrania was estimated to be 0.3% (95% CI, 0.2%-0.5%) among adult patients evaluated for headache in tertiary care with considerable heterogeneity (I2 = 76.4%). No cases with paroxysmal hemicrania were identified among 1,838 participants in a population-based sample. Moreover, the most prevalent cranial autonomic symptoms were lacrimation (77.3% [95% Cl, 62.7%-87.3%]), conjunctival injection (75.0% [95% Cl, 60.3%-85.6%]), and nasal congestion (47.7% [95% Cl, 33.6%-62.3%]). Our findings suggest that paroxysmal hemicrania is a rare disorder among adults evaluated for headache in tertiary care, while its prevalence in the general population remains unknown. Further studies focusing on the clinical features of paroxysmal hemicrania are warranted.

Paranoid psychosis after a single parenteral dose of indomethacin administered for headache diagnosis: A case and review of the literature

Background: Indomethacin is a non-steroidal anti-inflammatory used to diagnose and treat hemicrania continua and paroxysmal hemicrania. Treatment can be complicated by gastrointestinal adverse effects; less commonly reported are idiosyncratic neuropsychiatric adverse effects with indomethacin. Methods: A 50-year-old male with lateralized brief attacks of headache associated with cranial autonomic symptoms was administered a single 200 mg dose of intramuscular indomethacin. Within an hour, he developed acute psychosis, with paranoid delusions and verbal and physical aggression lasting 5 h, followed by recovery to baseline. We used search terms “indomethacin psychosis,” “indomethacin psychiatric,” “indomethacin side effects,” “non-steroidal anti-inflammatory psychosis,” and “non-steroidal anti-inflammatory psychiatric” within PubMed to identify previous reports and literature in this area. Results: Neuropsychiatric adverse effects of indomethacin have been reported since 1965 in a dose-dependent manner, usually with oral courses. They may be more common in the elderly, postpartum women and postoperative patients. Conclusion: Neuropsychiatric adverse effects should be considered in headache medicine, particularly in at-risk groups when indomethacin is administered. Patients, particularly those at highest risk, should be counseled about the risk of neuropsychiatric side effects on indomethacin which may be dose-dependent and are generally reversible on stopping the drug.

Paroxysmal hemicrania and hemicrania continua: Review on pathophysiology, clinical features and treatment.

Paroxysmal hemicrania and hemicrania continua are indometacin-sensitive trigeminal autonomic cephalalgias, a terminology which reflects the predominant distribution of the pain, observable cranial autonomic features and shared pathophysiology. Understanding the latter is limited, both by low prevalence and the intricacies of studying brain function, requiring multimodal techniques to glean insights into such disorders. Similarly obscure is the curious response to indometacin. This review will address what is currently known about pathophysiology, the rationale for the current classification and, features which may confound the diagnosis, such as lack of cranial autonomic symptoms and those which are typically associated with migraine such as nausea, photophobia, phonophobia and aura. Despite these characteristics, a dramatic response to indometacin, which is not seen in migraine nor the other trigeminal autonomic cephalalgias , provides the hallmark of the diagnosis. The main clinical differential for paroxysmal hemicrania is based on temporal pattern and lies between cluster headache and short-lasting-neuralgiform headache attacks with tearing or additional cranial autonomic symptoms. For hemicrania continua it is more challenging as the main differential for which the disorder is often treated is migraine. A prior episodic pattern, often days at a time, and the tendency to exacerbation with analgesics will further deflect from the diagnosis. The relevance of this is that there is little overlap in therapeutics between paroxysmal hemicrania and hemicrania continua and other headache disorders and there are limited effective alternatives to indometacin. The most effective are other non-steroidal anti-inflammatory drugs including the newer COX-II inhibitors. Even though early reports suggest that a higher indometacin dose-requirement may herald a secondary precipitating pathology, this does not seem to be the case, with syndrome and response to treatment being similar with the primary disorder. In this context imaging of new onset paroxysmal hemicrania or hemicrania continua and implication of the results will be discussed as will alternative treatment options.

Cigarette smoking history (personal and secondary childhood exposure) in non-cluster headache trigeminal autonomic cephalalgias: A clinic based study.

To look at cigarette smoking history (personal and secondary exposure as a child) in non-cluster headache trigeminal autonomic cephalalgias seen at a headache clinic and to determine smoking exposure prevalence utilizing previously published data. Retrospective chart review and PubMed/Google Scholar search. Forty-eight clinic patients met ICHD-3 criteria for non-cluster headache trigeminal autonomic cephalalgias. Four had paroxysmal hemicrania, 75% were smokers and secondary exposure was noted in all. 16 patients had short lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) or short lasting unilateral neuralgiform headache attacks with autonomic symptoms (SUNA), 12.5% were smokers and secondary exposure was noted in 91%. Twenty-eight patients had hemicrania continua, 21% were smokers and secondary exposure was found in 62.5%.Since 1974 there have been 88 paroxysmal hemicrania, 50 SUNCT or SUNA and 89 hemicrania continua patients with a documented smoking exposure history. From current data and previous studies, a smoking history was noted in 60% paroxysmal hemicrania, 18% SUNCT and SUNA and 21% hemicrania continua patients. A cigarette smoking history appears to be connected to paroxysmal hemicrania (personal and secondary exposure) and possibly to SUNCT/SUNA (secondary) and hemicrania continua (secondary).

Trigeminal Autonomic Cephalalgias and Neuralgias in Children and Adolescents: a Narrative Review.

To summarize the available literature as well as the authors' experience on trigeminal autonomic cephalalgias (TACs) and cranial neuralgias in children and adolescents. While TACs and cranial neuralgias are rare in children, several recent case series have been published. TACs in children share most of the clinical features of TACs in adults. However, there are many reported cases with clinical features which overlap more than one diagnosis, suggesting that TACs may be less differentiated in youth. Indomethacin-responsive cases of cluster headache and SUNCT/SUNA have been reported in children, whereas in adults indomethacin is usually reserved for paroxysmal hemicrania and hemicrania continua. Neuralgias appear to be rare in children. Clinical features are often similar to adult cases, though clinicians should maintain a high index of suspicion for underlying causes.

Pathophysiology of Primary Headache Syndrome: A Narrative Literature Review

Primary headache syndrome is a chronic recurrent type not associated with structural abnormalities or systemic disease and includes migraine, cluster, paroxysmal hemicrania, and tension headaches. This literature review aimed to describe the types of primary headaches and their pathophysiology. Migraine is an episodic neurological disorder characterized by headaches that last 4 to 72 hours. This disorder is diagnosed when two of the following features occur: unilateral headache, throbbing pain, the pain worsening with activity, moderate or severe pain intensity, and at least one of the following: nausea and/or vomiting, or photophobia and phonophobia. Cluster headaches are one of a group of rare disorders known as trigeminal autonomic cephalgia. Tension-type headache (TTH) is the most common type of recurring headache. It's not a vascular headache or a migraine. The mean age of onset is during the second decade of life. Usually mild to moderate bilateral headaches with a feeling of tight bands or pressure around the head.

Long term outcomes of occipital nerve stimulation.

Occipital nerve stimulation (ONS) has been investigated as a potential treatment for disabling headaches and has shown promise for disorders such as chronic migraine and cluster headache. Long term outcomes stratified by headache subtype have had limited exploration, and literature on outcomes of this neuromodulatory intervention spanning 2 or more years is scarce. We performed a narrative review on long term outcomes with ONS for treatment of headache disorders. We surveyed the available literature for studies that have outcomes for 24 months or greater to see if there is a habituation in response over time. Review of the literature revealed evidence in treatment of occipital neuralgia, chronic migraine, cluster headache, cervicogenic headache, short lasting unilateral neuralgiform headache attacks (SUNHA) and paroxysmal hemicrania. While the term "response" varied per individual study, a total of 17 studies showed outcomes in ONS with long term sustained responses (as defined per this review) in the majority of patients with specific headache types 177/311 (56%). Only 7 studies in total (3 cluster, 1 occipital neuralgia, 1 cervicogenic headache, 1 SUNHA, 1 paroxysmal hemicrania) provided both short-term and long-term responses up to 24 months to ONS. In cluster headache, the majority of patients (64%) were long term responders (as defined per this review) and only a minority of patients 12/62 (19%) had loss of efficacy (e.g., habituation). There was a high number 313/439 (71%) of adverse events per total number of patients in the studies including lead migration, requirements of revision surgery, allergy to surgical materials, infection and intolerable paresthesias. With the evidence available, the response to ONS was sustained in the majority of patients with cluster headache with low rates of loss of efficacy in this patient population. There was a high percent of adverse events per number of patients in long term follow-up and likely related to the off-label use of leads typically used for spinal cord stimulation. Further longitudinal assessments of outcomes in occipital nerve stimulation with devices labelled for use in peripheral nerve stimulation are needed to evaluate the extent of habituation to treatment in headache.

Non-invasive neuromodulation of the cervical vagus nerve in rare primary headaches.

Primary headache disorders can be remarkably disabling and the therapeutic options available are usually limited to medication with a high rate of adverse events. Here, we discuss the mechanism of action of non-invasive vagal nerve stimulation, as well as the findings of the main studies involving patients with primary headaches other than migraine or cluster headache, such as hemicrania continua, paroxysmal hemicrania, cough headache, or short-lasting neuralgiform headache attacks (SUNCT/SUNA), in a narrative analysis. A bibliographical search of low-prevalence disorders such as rare primary headaches retrieves a moderate number of studies, usually underpowered. Headache intensity, severity, and duration showed a clinically significant reduction in the majority, especially those involving indomethacin-responsive headaches. The lack of response of some patients with a similar diagnosis could be due to a different stimulation pattern, technique, or total dose. The use of non-invasive vagal nerve stimulation for the treatment of primary headache disorders represents an excellent option for patients with these debilitating and otherwise refractory conditions, or that cannot tolerate several lines of preventive medication, and should always be considered before contemplating invasive, non-reversible stimulation techniques.

Gray Zones in the Trigeminal Autonomic Cephalalgias

Background: Limited data are available about the importance of migrainous features of the trigeminal autonomic cephalalgias (TACs). Methods: We enrolled 99 patients with TACs including 71 cluster headaches, 11 with short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing, 10 with paroxysmal hemicrania, and seven with hemicrania continua. The presence of diagnostic migraine criteria such as throbbing headache, nausea and/or vomiting, photophobia, phonophobia, and aggravation by physical activity was questioned in these patients as well as autonomic features. Furthermore, supportive features of migraine including motion sickness, atopy and allergy, exacerbation during menstrual periods, irregular sleep, dizziness, and family history of any primary headache were noted. Results: The most common cranial autonomic symptom was lacrimation (87.9%) and the most common migrainous features were throbbing headache (51.5%), phonophobia (41.4%), nausea (39.4%), and photophobia (34.3%). Family history of any primary headache (25.3%) and atopy and allergy (13.1%) was the most common supportive features. Conclusion: We found higher percentages of migrainous features in patients with TACs; phonophobia, throbbing headache, and nausea frequently accompanied TACs. Aggravation by physical activity, which is one of the diagnostic migraine criteria, and motion sickness, which is one of the supportive features of migraine, were much lower in patients with TAC compared with migraineurs.