Medication Overuse Headache: an Updated Review and Clinical Recommendations on Management.

OVERVIEW: Medication overuse headache (MOH) is highly prevalent among individuals with primary headache disorders. PURPOSE OF REVIEW: (1) Provide an update on epidemiology, risk factors, and treatment strategies of MOH and (2) provide recommendations on the management of MOH. RECENT FINDINGS: The prevalence of MOH ranges from 0.5 to 7.2%. Risk factors for MOH include female sex, lower socioeconomic status, some psychiatric conditions, and substance use disorders, among others. Recent large clinical trials support preventative therapy as an integral component of MOH management. Emerging clinical trial evidence supports anti-CGRP mAbs as effective preventative treatments among individuals with migraine and MOH. Among the large clinical trials, candesartan, topiramate, amitriptyline, and onabotulinumtoxinA were the most used preventative therapies, providing further support for these agents. MOH management requires a multifaceted and patient-centered approach that involves patient education, behavioral interventions, withdrawal of the overused medication, and initiation of preventative medication.

Secondary Headache Disorders: Approach, Workup, and Special Considerations for Select Populations.

Headache is one of the most common diagnoses in neurology. A thorough understanding of the clinical presentation of secondary headache, which can be life-threatening, is critical. This review provides an overview of the diagnostic approach to a patient with headache, including discussion of "red," "orange," and "green" flags. We emphasize particular scenarios to help tailor the clinical workup to individual circumstances such as in pregnant women, when particular attention must be paid to the effects of blood pressure and hypercoagulability, as well as in older adults, where there is a need for higher suspicion for an intracranial mass lesion or giant cell arteritis. Patients with risk factors for headache secondary to alterations in intracranial pressure, whether elevated (e.g., idiopathic intracranial hypertension) or decreased (e.g., cerebrospinal fluid leak), may require more specific diagnostic testing and treatment. Finally, headache in patients with COVID-19 or long COVID-19 is increasingly recognized and may have multiple etiologies.

Single-Pulse Transcranial Magnetic Stimulation for the preventive treatment of difficult-to-treat migraine: a 12-month prospective analysis.

BACKGROUND: Initial evidence have shown the short-term efficacy of sTMS in the acute and preventive treatment of migraine. It is unknown whether this treatment approach in the long-term is effective and well tolerated in difficult-to-treat migraine. METHODS: This is a prospective, single centre, open-label, real-world analysis conducted in difficult-to-treat patients with high-frequency episodic migraine (HFEM) and chronic migraine (CM) with and without medication overuse headache (MOH), who were exposed to sTMS therapy. Patients responding to a three-month sTMS treatment, continued the treatment and were assessed again at month 12. The cut-off outcome for treatment continuation was reduction in the monthly moderate to severe headache days (MHD) of at least 30% (headache frequency responders) and/or a ≥ 4-point reduction in headache disability using the Headache Impact test-6 (HIT-6) (headache disability responders). RESULTS: One hundred fifty-three patients were included in the analysis (F:M = 126:27, median age 43, IQR 32.3-56.8). At month 3, 93 out of 153 patients (60%) were responders to treatment. Compared to baseline, the median reduction in monthly headache days (MHD) for all patients at month 3 was 5.0 days, from 18.0 (IQR: 12.0-26.0) to 13.0 days (IQR: 5.75-24.0) (P = 0.002, r = - 0.29) and the median reduction in monthly migraine days (MMD) was 4.0 days, from 13.0 (IQR: 8.75-22.0) to 9.0 (IQR: 4.0-15.25) (P = 0.002, r = - 0.29). Sixty-nine out of 153 patients (45%) reported a sustained response to sTMS treatment at month 12. The percentage of patients with MOH was reduced from 52% (N = 79/153) at baseline to 19% (N = 29/153) at month 3, to 8% (N = 7/87) at month 12. There was an overall median 4-point reduction in HIT-6 score, from 66 (IQR: 64-69) at baseline to 62 at month 3 (IQR: 56-65) (P < 0.001, r = - 0.51). A total of 35 mild/moderate adverse events were reported by 23 patients (15%). One patient stopped sTMS treatment due to scalp sensitivity. CONCLUSIONS: This open label analysis suggests that sTMS may be an effective, well-tolerated treatment option for the long-term prevention of difficult-to-treat CM and HFEM.

Spontaneous intracranial hypotension: the role of radiology in diagnosis and management.

Spontaneous intracranial hypotension (SIH) is a condition that results from leakage of cerebrospinal fluid (CSF) from the spine, and which typically presents with debilitating orthostatic headache, but can be associated with a wide range of other symptoms. The causes of spontaneous CSF leaks that lead to SIH include dural tears, leaking meningeal diverticula, and CSF-venous fistulas. Imaging plays a central role in the initial diagnosis of SIH and in its subsequent investigation and management. This article reviews the typical neuroimaging manifestations of SIH and discusses the utility of different myelographic techniques for localising spinal CSF leaks as well as the role of image-guided treatment.

Medication overuse headache in patients with chronic migraine using cannabis: A case-referent study.

OBJECTIVE: To examine whether cannabis use predicts medication overuse headache (MOH) in patients with chronic migraine (CM). METHODS: Electronic chart review was conducted by combining the terms "CM," "medication overuse," "cannabis," "cannabidiol," and "tetrahydrocannabinol" for patients seen at our headache clinics from 2015 to 2019. Of 729 charts consecutively screened, 368 met our inclusion criteria, that is, adult patients with CM with ≥1-year CM duration. The following variables were extracted from the included patient charts: MOH diagnosis, age, sex, migraine frequency, current CM duration, current cannabis use duration, overused acute migraine medications, current MOH duration, and types of cannabis products used. Logistic regression was used to identify variables predicting MOH while controlling for remaining predictors. Agglomerative hierarchical clustering (AHC) was conducted to explore natural clusters using all predictor variables. RESULTS: There were 212 patients with CM and MOH (cases; median age 43 years, interquartile range [IQR] 33-54; 177 [83%] females) and 156 patients with CM without MOH (referents; median age 40 years, IQR 31-49; 130 [83%] females). MOH was present in 81% (122/150) of current cannabis users compared with 41% (90/218) in those without cannabis use-adjusted odds ratio 6.3 (95% CI: 3.56 to 11.1, p < 0.0001). Current cannabis use was significantly associated with opioid use (Spearman's rho 0.26, p < 0.0001). Both current cannabis use (rho 0.40, p < 0.0001) and opioid use (rho 0.36, p < 0.0001) were significantly associated with MOH. Similarly, AHC revealed two major natural clusters. Cluster I patients featured 9.3 times higher current cannabis use, 9.2 times higher current opioid use, and 1.8 times higher MOH burden than those in Cluster II (p < 0.0001). CONCLUSION: Cannabis use was significantly associated with increased prevalence of MOH in CM. Bidirectional cannabis-opioid association was observed-use of one was associated with use of the other. Advising patients with CM and MOH to reduce cannabis use may help treat MOH effectively.

Headache in transgender and gender-diverse patients: A narrative review.

OBJECTIVE: To summarize the unique aspects of managing headache in gender minorities and current research in this area including the potential relationship between gender-affirming hormone therapy (GAHT) and headache. BACKGROUND: The study of headache in gender minorities is intrinsically important. Gender minorities are medically underserved, and their medical care to date has been limited by socioeconomic disadvantages including stigma and an unsupportive clinical environment. Despite the rising population of transgender and gender-diverse adults and youth, headache research has also been limited. Knowledge of hormonal effects on headache in cisgender patients raises the question of possible effects of GAHT on transgender patients. METHODS/RESULTS: The manuscript is a narrative review of current best practices in treating transgender patients, including the use of appropriate terminology and ways to create a supportive environment. It also contains current guidelines on GAHT and reviews drug-drug interactions and secondary headache related to hormone therapy. We also review transgender headache research and related research on hormonal effects on headache in cisgender individuals. CONCLUSION: Creating a supportive environment for transgender and gender-diverse patients and being knowledgeable about GAHT are key to providing quality headache care. This review identifies further research needs for this population including the epidemiology of headache disorders in sexual minorities and the potential effects of GAHT on headache disorders in transgender patients.

Post-traumatic headache attributed to traumatic brain injury: classification, clinical characteristics, and treatment.

Post-traumatic headache is a common sequela of traumatic brain injury and is classified as a secondary headache disorder. In the past 10 years, considerable progress has been made to better understand the clinical features of this disorder, generating momentum to identify effective therapies. Post-traumatic headache is increasingly being recognised as a heterogeneous headache disorder, with patients often classified into subphenotypes that might be more responsive to specific therapies. Such considerations are not accounted for in three iterations of diagnostic criteria published by the International Headache Society. The scarcity of evidence-based approaches has left clinicians to choose therapies on the basis of the primary headache phenotype (eg, migraine and tension-type headache) and that are most compatible with the clinical picture. A concerted effort is needed to address these shortcomings and should include large prospective cohort studies as well as randomised controlled trials. This approach, in turn, will result in better disease characterisation and availability of evidence-based treatment options.

Breaking the cycle of medication overuse headache.

Care of this disorder can be complex-from ruling out another secondary cause of headache to supervising detox from abortives, providing preventives, and educating often-fearful patients.

Secondary stabbing headache associated with intracranial tumors, aneurysms, and arteriovenous malformation: An alarming warning sign.

BACKGROUND: Stabbing headache (SH) is considered as a pure primary headache, but according to a few clinical observations it could also be secondary. Over the past decades, we have been observing the complaint of SH in patients with intracranial vascular and neoplastic lesions. OBJECTIVE: To describe a series of patients with intracranial lesions who experienced SH. METHODS: This is a cross-sectional, retrospective study of 34 patients with intracranial lesions associated with SH, admitted at Hospital das Clínicas, Federal University of Pernambuco, Brazil. RESULTS: In this series of 34 patients [29 women, 44 ± 12 years (mean ± SD)] with secondary SH, the causes were intracranial neoplasms (n = 31), cerebral aneurysms (n = 2), or arteriovenous malformation (n = 1). Pituitary tumor (n = 18), meningioma (n = 6), and vestibular schwannomas (n = 4) were the most prevalent types of intracranial neoplasms. All these lesions had intimate contact with the dura mater, including an oligodendroglioma, the only intra-axial tumor in the series. A characteristic in the secondary SH is the crescendo pattern (12/34, 35%), progressing from infrequent attacks to recurrent crises occurring several times a day. The SH lasted from 5 days to 60 months (15 ± 18 months, mean ± SD) until the correct diagnosis [16/34 (47%) of the patients ≤6 months]. The SH was triggered by the movement of the head (5/34, 15%) or Valsalva maneuver (1/34). After surgery, suppression of the SH was observed. In a few of the patients to whom dexamethasone was prescribed, the SH subsided within a few days. CONCLUSION: This study was able to identify clinical red flags associated with intracranial lesions and secondary SH, for example, recent onset of SH, exclusively unilateral (ipsilateral) at the same location, crescendo pattern, triggered by head movements, or Valsalva maneuver.

Secondary headache attributed to exposure to or overuse of a substance.

BACKGROUND: Secondary headaches attributed to exposure to or the overuse of a substance are classified under chapter eight in the International Classification of Headache Disorders 3rd edition. Three distinct sub-chapters consider: 1. Headache attributed to exposure to a substance, 2. Medication overuse headache, and 3. Headache attributed to substance withdrawal. Headache attributed to exposure to a substance refers to a headache with onset immediately or within hours after the exposure, while medication overuse headache is a headache occurring on 15 or more days per month that has developed as a consequence of regular usage of acute headache medication(s) for more than three consecutive months in a patient with a pre-existing primary headache disorder. The withdrawal of caffeine, oestrogen, and opioids is most often associated with the development of headache. DISCUSSION: Despite the current headache classification, there is no certainty of a causal relationship between the use of any substance and the development of headache. Some substances are likely to provoke headache in patients that suffer from a primary headache disorder like migraine, tension-type headache or cluster headache, while others were described to cause headache even in people that generally do not get headaches. Toxic agents, such as carbon monoxide (CO) are difficult to investigate systematically, while other substances such as nitric oxide (NO) were specifically used to induce headache experimentally. If a patient with an underlying primary headache disorder develops a headache, in temporal relation to exposure to a substance, which is significantly worse than the usual headache it is considered secondary. This is even more the case if the headache phenotype is different from the usually experienced headache characteristics. Medication overuse headache is a well-described, distinct disease entity with only marginally understood pathophysiology and associated psychological factors. Managing medication overuse headache patients includes education, detoxification, prophylactic treatments and treating comorbidities, which is reflected in available guidelines. Viewing medication overuse headache as a separate entity helps clinicians and researchers better recognise, treat and study the disorder. CONCLUSION: Identification of substances that may cause or trigger secondary headache is important in order to educate patients and health care professionals about potential effects of these substances and prevent unnecessary suffering, as well as deterioration in quality of life. Treatment in case of medication overuse and other chronic headache should be decisive and effective.

Erenumab for headaches in idiopathic intracranial hypertension: A prospective open-label evaluation.

OBJECTIVE: To determine the effectiveness of erenumab in treating headaches in idiopathic intracranial hypertension (IIH) in whom papilledema had resolved. BACKGROUND: Disability in IIH is predominantly driven by debilitating headaches with no evidence for the use of preventative therapies. Headache therapy in IIH is an urgent unmet need. METHODS: A prospective, open-label study in the United Kingdom was conducted. Adult females with confirmed diagnosis of IIH now in ocular remission (papilledema resolved) with chronic headaches (≥15 days a month) and failure of ≥3 preventative medications received erenumab 4-weekly (assessments were 3-monthly). The primary end point was change in monthly moderate/severe headache days (MmsHD) from baseline (30-day pretreatment period) compared to 12 months. RESULTS: Fifty-five patients, mean (SD) age 35.3 (9) years and mean duration of headaches 10.4 (8.4) years with 3.7 (0.9) preventative treatment failures, were enrolled. Mean baseline MmsHD was 16.1 (4.7) and total monthly headache days (MHD) was (29) 2.3. MmsHD reduced substantially at 12 months by mean (SD) [95% CI] 10.8 (4.0) [9.5, 11.9], p < 0.001 and MHD reduced by 13.0 (9.5) [10.2, 15.7], p < 0.001. Crystal clear days (days without any head pain) increased by 13.1 (9.5) [9.6, 15.3], p < 0.001, headache severity (scale 0-10) fell by 1.3 (1.7) [0.9, 1.9], p < 0.001, and monthly analgesic days reduced by 4.3 (9.2) [1.6, 6.9], p = 0.002. All these measures had improved significantly by 3 months, with a consistent significant response to 12 months. Headache impact test-6 score and quality of life Short Form-36 Health Survey significantly improved at 12 months. Sensitivity analysis revealed similar results for patients with and without a prior migraine diagnosis (28/55 (52%) patients) or those with or without medication overuse (27/55 (48%) patients). CONCLUSIONS: This study provides evidence for the effectiveness of erenumab to treat headaches in IIH patients with resolution of papilledema. It provides mechanistic insights suggesting that calcitonin gene-related peptide is likely a modulator driving headache and a useful therapeutic target.

Secondary Headache: Current Update.

PURPOSE: The purpose of this paper is to review some of the causes of secondary headache particularly focusing on the subcategories of secondary headache in the International Classification of Headache Disorders, 3rd edition, the clinical features of these headaches, and their associated features and management. OVERVIEW: Headache attributed to trauma or injury to the head and/or neck, headache attributed to cranial or cervical vascular disorder, headache attributed to non-vascular intracranial disorder, headache attributed to a substance or its withdrawal, headache attributed to infection, headache attributed to disorder of homeostasis, and headache or facial pain attributed to disorder of the cranium, neck, eye, ears, nose, sinuses, teeth, mouth, or other facial or cervical structure are discussed in this paper. DISCUSSION: Headache is a common symptom of multiple medical conditions. Although a minority of headache patients have a secondary basis for their headaches, it is important to identify clinical features of secondary headache disorders including both the headache and non-headache features of the condition, diagnose the secondary etiology correctly, and treat them appropriately.

Frequency and Type of Red Flags in Patients With Covid-19 and Headache: A Series of 104 Hospitalized Patients.

OBJECTIVE: In this study, we aimed to evaluate the frequency of the main red flags in patients with headache who do have Covid-19. BACKGROUND: Headache is one of the most frequent neurologic symptoms of Coronavirus disease 2019 (Covid-19). Diagnosis of secondary headache disorders is still based on the presence of red flags. DESIGN AND METHODS: Cross-sectional study of hospitalized patients with confirmed Covid-19 disease. We interrogated every patient about the presence of headache and if so, a headache expert conducted a structured interview assessing the presence and type of the main red flags. We evaluated the presence of laboratory abnormalities on admission. RESULTS: We screened 576 consecutive patients, 130/576 (22.6%) described headache, and 104 were included in the study. Mean age of patients was 56.7 (standard deviation: 11.2) and 66/104 (63.4%) were female. Red flags concerning prior medical history were present in 79/104 (76.0%) cases, and those related to the headache itself were observed in 99/104 (95.2%) patients. All patients 104/104 (100%) described systemic symptoms and 86/104 (82.7%) some neurologic symptoms. Laboratory results were abnormal in 98/104 (94.2%) cases. The most frequent red flags were fever, in 93/104 (89.4%) patients, cough, in 89/104 (85.6% cases), and increased C-reactive protein in 84/100 (84.0%) cases. CONCLUSION: In patients with Covid-19 that described the headache red flags were present in most cases. There was not any universal red flag, being necessary the comprehensive evaluation of all of them.

Case Series of Headache Characteristics in COVID-19: Headache Can Be an Isolated Symptom.

Headache was reported in up to one-third of the hospitalized patients; yet, the clinical characteristics of headache associated with coronavirus disease 2019 (COVID-19) have not been defined. This observational case study included patients who were consulted to headache unit due to headache and had COVID-19 illness. Headache features in 13 PCR-confirmed COVID-19 patients with mild symptoms were reported. Headache was the isolated symptom of the COVID-19 in 3 patients and emerged as an early symptom during the disease course in all patients. Patients specified severe, rapid onset, unrelenting headache with migraine-like features, as well as unusual sensory symptoms such as anosmia, and gastrointestinal symptoms such as diarrhea and loss of appetite and weight. Headache lasted up to 3 days in 70% of the patients and resolved in all patients within 2 weeks. Despite the fact that most of the patients were female and headache characteristics were suggestive of migraine, majority of patients were not suffering from primary headaches. It was concluded that headache could be an isolated symptom of COVID-19, which might possibly be ignored in asymptomatic patients. Headaches associated with COVID-19 included features resembling migraine and/or atypical symptoms including anosmia and diarrhea.