Complementary and Integrative Medicine for the Treatment of Trigeminal Neuralgia and Trigeminal Autonomic Cephalalgia.

PURPOSE OF REVIEW: Trigeminal neuralgia (TN) and trigeminal autonomic cephalalgias (TACs) are both painful diseases which directly impact the branches of the trigeminal nerve, which supply the face. Patients who have experienced adverse effects, have not responded to mainstream treatments, or have a personal preference for nonmedication options, often turn to complementary and integrative medicine (CIM). The aim of this review is to discuss the efficacy and safety of CIM therapies available for the treatment of TN and TACs. RECENT FINDINGS: Not only are there limited therapeutic options for TN and TAC patients, but also is there a proportion of patients who are intolerant to standard medical treatments. Recent findings have illustrated that 86% of patients with headache disorders utilize CIM modalities in combination with mainstream medical therapy. CIM modalities can be helpful for these diseases and have primarily been studied in combination with standard medical therapy. There is limited evidence for CIM and behavioral therapies in managing these conditions, and more research is needed to confirm which therapies are safe and effective.

Multimodal Migraine Management and the Pursuit of Migraine Freedom: A Narrative Review.

Migraine is a neurologic disease with a complex pathophysiology that can be controlled with current treatment options but not cured. Therefore, treatment expectations are highly variable. The concept of migraine freedom was recently introduced and can mean different things, with some, for example, expecting complete freedom from headache and associated symptoms and others accepting the occasional migraine attack if it does not impact functioning. Therefore, migraine management should be optimized so that patients can have the best opportunity to achieve their optimal treatment goals. With migraine freedom as a goal and, given the complex pathophysiology of migraine and the high incidence of comorbidities among individuals with migraine, treatment with a single modality may be insufficient, as it may not achieve migraine freedom in those with more frequent or disabling attacks. In this clinical perspective article, we have identified four key, partially overlapping principles of multimodal migraine treatment: (1) manage common comorbidities; (2) control modifiable risk factors for progression by addressing medication and caffeine overuse; (3) diagnose and treat secondary causes of headache, if present; and (4) individualize acute and preventive treatments to minimize pain, functional disability, and allodynia. There are many barriers to pursuing migraine freedom, and strategies to overcome them should be optimized. Migraine freedom should be an aspirational goal both at the individual attack level and for the disease overall. We believe that a comprehensive and multimodal approach that addresses all barriers people with migraine face could move patients closer to migraine freedom.

Migraine treatment with external concurrent occipital and trigeminal neurostimulation-A randomized controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of concurrent non-invasive stimulation of occipital and trigeminal nerves in acute treatment of migraine with or without aura. BACKGROUND: Non-invasive neuromodulation devices stimulating a single peripheral nerve or anatomic distribution are routinely used by patients with migraine refractory to the first-line drugs or those who opt out of pharmaceutical treatment. Concurrent occipital and trigeminal stimulation was described in an invasive setting, and its safety cost outweighed its efficacy gain. This study evaluated the efficacy and safety of an external concurrent occipital and trigeminal device in acute treatment of migraine. DESIGN AND METHODS: This was a randomized, sham-controlled, double-blind, multi-center trial. Patients 18 years of age or older who met the International Classification of Headache Disorders (2018) diagnostic criteria for migraine with or without aura, reported 1-6 migraine attacks per month, and other headaches no more than 6 days per month were enrolled. Of 131 intention-to-treat participants (67 and 64 in the active and sham groups, respectively), 109 (50 and 59 in the active and sham groups, respectively) treated at least one migraine episode. Reduction of migraine headache (pain relief) 2 h after treatment initiation was the primary efficacy endpoint. Pain relief at 1 h, and pain freedom and relief in most bothersome symptom at 2 h after treatment initiation were the secondary endpoints. Freedom from most bothersome symptom at 2 h and sustained pain freedom 24 h after treatment initiation were among the exploratory endpoints. RESULTS: Sixty percent of participants (30/50) in the active arm reported pain relief at 2 h after initiation of the first eligible treatment (primary outcome) compared to 37% (22/59) in the control arm (difference, 23%; 95% confidence interval [CI], 2%-41%; p = 0.018). Pain freedom at 2 h without rescue medication was reported by 46% (23/50) of participants in the active arm and by 12% (7/59) of participants in the sham arm (p < 0.001). Pain freedom 2 h after the treatment and, subsequently, at 24 h, was reported by 4.25 times more participants in the active arm (36%; 18/50) than in the sham arm (8%; 5/59). The 28% difference was statistically significant (95% CI, 1%-43%; p < 0.001). A 4.25-fold difference was also observed comparing the proportion of participants free from pain and most bothersome symptom 2 h after the stimulation (47% [17/36] and 11% [5/45] in the active and sham arms, respectively; 95% CI, 14%-54%; p < 0.001). Adverse events were not serious or severe. All study-related events resolved without treatment. CONCLUSION: External concurrent occipital and trigeminal neurostimulation is a well-tolerated, safe, and effective migraine treatment that provided a fast and durable relief and freedom from migraine pain and associated symptoms in a randomized setting. The observed safety and performance suggest external concurrent occipital and trigeminal neurostimulation is a viable alternative to the currently available acute migraine treatments. TRIAL REGISTRATION: clinicaltrials.gov identifier NCT03631550.

Integrative, Interventional, and Non-invasive Approaches for the Treatment for Migraine During Pregnancy.

PURPOSE OF REVIEW: While most women with migraine improve during pregnancy, a subset may remain unchanged or even become more severe. Given the limited evidence for the use of prescription medications during pregnancy, many look to other treatment modalities. We seek to review complementary and integrative medicine, procedural interventions, and neurostimulation to empower women with safe and effective treatment options during pregnancy. RECENT FINDINGS: Migraine treatment during pregnancy remains controversial. While evidence is limited, prospective and retrospective reviews, as well as clinical experience support the use of nutraceuticals, procedural interventions, and neurostimulation during pregnancy when the appropriate risks and benefits are weighed. Empowering patients with information on complementary and integrative medicine, as well as non-systemic and interventional treatments, may help to reduce anxiety and headache burden during pregnancy. Various nutraceuticals have shown promise for the preventive management of migraine. Non-systemic interventions such as trigger point injections and peripheral and sphenopalatine nerve blocks offer effective treatment options with minimal side-effects. Options for neurostimulation have expanded in recent years and may offer safe and effective non-pharmacologic options for the management of migraine. It is imperative that providers do not minimize migraine during pregnancy and become aware of the treatment modalities available to help guide women through this experience.

Phase 3 randomized, double-blind, sham-controlled Trial of e-TNS for the Acute treatment of Migraine (TEAM).

Migraine is one of the most common and debilitating neurological disorders worldwide. External Trigeminal Nerve Stimulation (e-TNS) is a non-pharmacological, non-invasive therapeutic alternative for patients with migraine. The TEAM study was a prospective, multicenter, randomized, double-blind, sham-controlled, Phase 3 trial for 2-h, continuous, e-TNS treatment of a single moderate or severe migraine attack at home. A total of 538 adults meeting the International Classification of Headache Disorders 3rd edition criteria for 2-8 migraine headache days per month were recruited and randomized in a 1:1 ratio to 2-h active or sham stimulation. Migraine pain levels and most bothersome migraine-associated symptoms (MBS) were recorded at baseline, 2 h, and 24 h using a paper diary. The primary endpoints for the study were pain freedom at 2 h and freedom from the MBS at 2 h. The secondary endpoints were pain relief at 2 h, absence of most bothersome migraine-associated symptoms (MBSs) at 2 h, acute medication use within 24 h after treatment, sustained pain freedom at 24 h, and sustained pain relief at 24 h. Adverse event data was also collected and compared between groups. Five hundred thirty-eight patients were randomized to either the verum (n = 259) or sham (n = 279) group and were included in an intention-to-treat analysis. The percentage of patients with pain freedom at 2 h was 7.2% higher in verum (25.5%) compared to sham (18.3%; p = 0.043). Resolution of most bothersome migraine-associated symptom was 14.1% higher in verum (56.4%) compared to sham (42.3%; p = 0.001). With regards to secondary outcomes, pain relief at 2 h was 14.3% higher in verum (69.5%) than sham (55.2%; p = 0.001), absence of all migraine-associated symptoms at 2 h was 8.4% higher in verum (42.5%) than sham (34.1%; p = 0.044), sustained pain freedom and pain relief at 24 h was 7.0% and 11.5% higher in verum (22.8 and 45.9%) than sham (15.8 and 34.4%; p = 0.039 and .006, respectively). No serious adverse events were reported. Treatment with 2-h e-TNS is a safe and effective, non-invasive, and non-pharmacological alternative for the acute treatment of migraine attacks in an at-home setting.Trial registration Clinicaltrials.gov Identifier: NCT03465904. Registered 14/03/2018. https://www.clinicaltrials.gov/ct2/show/record/NCT03465904 .

Essential components of care in a multidisciplinary headache center: Perspectives from headache neurology specialists.

BACKGROUND AND OBJECTIVE: Comprehensive headache care involves numerous specialties and components that have not been well documented or standardized. This study aimed to elicit best practices and characterize important elements of care to be provided in multidisciplinary headache centers. METHODS: Qualitative, semi-structured telephone interviews with a purposive sample of headache neurology specialists from across the US, using open-ended questions. Interviews were recorded, transcribed, and coded. Coded data were further analyzed using immersion/crystallization techniques for final interpretation. RESULTS: Mean years providing headache care was 17.7 (SD = 10.6). Twelve of the 13 participants held United Council for Neurologic Subspecialties headache certification. Six described their practice site as providing multidisciplinary headache care. Participants explained most of their patients had seen multiple doctors over many years, and had tried numerous unsuccessful treatments. They noted patients with chronic headache frequently present with comorbidities and become stigmatized. All participants asserted successful care depends on taking time to talk with and listen to patients, gain understanding, and earn trust. All participants believed multidisciplinary care is essential within a comprehensive headache center, along with staffing enough headache specialists, implementing detailed headache intake and follow-up protocols, and providing the newest medications, neuromodulation devices, botulinum toxin injections, monoclonal antibodies, nerve blocks and infusions, and treatment from a health psychologist. Other essential services for a headache center are other behavioral health practitioners providing cognitive behavioral therapy, mindfulness, biofeedback and pain management; and autonomic neurology, neuropsychology, vestibular audiology, sleep medicine, physical therapy, occupational therapy, exercise physiology, speech therapy, nutrition, complementary integrative health modalities, and highly trained support staff. CONCLUSION: While headache neurology specialists form the backbone of headache care, experts interviewed for this study maintained their specialty is just one of many types of care needed to adequately treat patients with chronic headache, and this is best provided in a comprehensive, multidisciplinary center.

Preventing the Progression of Episodic Migraine to Chronic Migraine with Acute Treatment Optimization.

PURPOSE OF REVIEW: To evaluate the evidence regarding acute migraine treatment optimization to prevent the progression of episodic migraine to chronic migraine. This review also provides a summary of evidence-based acute migraine treatments and how to tailor a regimen based on an individual patient's needs. RECENT FINDINGS: Several acute migraine treatments have been food and drug administration (FDA)-approved since 2020. This review summarizes pain freedom data at 2 h for these medications and devices and examines the classic acute migraine treatments. This review presents the existing data about acute treatment optimization and its preventive role in the progression of episodic migraine to chronic migraine. We present updated clinical trial efficacy endpoints from the American Headache Society (AHS) and the FDA and review the evidence for acute migraine treatments currently available in clinical practice.

Complementary and integrative medicine perspectives among veteran patients and VHA healthcare providers for the treatment of headache disorders: a qualitative study.

OBJECTIVE: To evaluate veteran patient and provider perceptions and preferences on complementary and integrative medicine (CIM) for headache management. BACKGROUND: The Veterans Health Administration (VHA) has spearheaded a Whole Health system of care focusing on CIM-based care for veteran patients. Less is known about patients' and providers' CIM perceptions and preferences for chronic headache management. METHODS: We conducted semi-structured interviews with 20 veteran patients diagnosed with headache and 43 clinical providers, across 12 VHA Headache Centers of Excellence (HCoE), from January 2019 to March 2020. We conducted thematic and case comparative analyses. RESULTS: Veteran patients and VHA clinical providers viewed CIM favorably for the treatment of chronic headache. Specific barriers to CIM approaches included: (1) A lack of personnel specialized in specific CIM approaches for timely access, and (2) variation in patient perceptions and responses to CIM treatment efficacy for headache management. CONCLUSION: Veteran patients and VHA clinical providers in this study viewed CIM favorably as a safe addition to mainstream headache treatments. Advantages to CIM include favorable adverse effect profiles and patient autonomy over the treatment. By adding more CIM providers and resources throughout the VHA, CIM modalities may be recommended more routinely in the management of veterans with headache.

A patient perspective of complementary and integrative medicine (CIM) for migraine treatment: a social media survey.

To survey persons with migraine who use social media about Complementary and Integrative Medicine (CIM) for the treatment of migraine. BACKGROUND: CIM encompasses medical treatments that are not part of but are used in concert with mainstream medicine. Between 28 and 82% of people with migraine use non-drug approaches, and approximately 50% of people with migraine do not discuss non-drug treatments with their healthcare providers (HCPs). It is important for providers to be conversant with CIM treatments and the available evidence-based data. To further this effort, people with migraine were surveyed directly through social media to identify CIM practices in which they engage. METHODS: In collaboration with the American Migraine foundation (AMF) and Yakkety Yak, a digital marketing agency, we conducted a cross-sectional survey study. Participants were recruited from the Move Against Migraine (MAM) Facebook group which has 20,000+ members. The goals of the survey were to assess the attitudes toward CIM among this group, to identify which CIM modalities are being used and to determine what patients considered to be the most effective CIM modalities. While Yakkety Yak posted the survey link on the group page, the survey itself was hosted on Qualtrics, a confidential survey service. RESULTS: 372 MAM members (approximately 2%) responded to the questionnaire, of which 335 reported using CIM; between 114 and 139 (34-42%) found CIM modalities to be at least mildly effective. Of note, 164 (49%) reported using cannabis derivatives or cannabinoids, specifically with, 64/164 (39%) reporting that cannabis was not effective for them. CONCLUSIONS: This study provides an initial investigation into the demographic and practice patterns of migraine patients who use CIM. While this sampling may not reflect CIM use across all individuals with migraine, it does strongly suggest the need for better education on the role of, and evidence for, CIM among headache care providers, and the need to ask patients specifically about their use of and interest in CIM.

Headache in Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Narrative Review.

OBJECTIVE: To summarize available literature regarding headache as a manifestation of coronaviruses and to describe potential underlying mechanisms. REVIEW METHODS: References for this review were identified by searches within PubMed without any date restrictions. The search terms used were coronavirus disease 2019 (COVID-19) clinical manifestation, COVID-19 epidemiology, neurologic findings in COVID-19, headache in COVID-19, neurologic manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and headache in SARS-CoV-2. RESULTS: Headache is one of the most common neurologic complaints in patients with SARS-CoV-2. While the pathophysiological connection between headache and SARS-CoV-2 is unclear, inflammatory mechanisms may play a key role. One of the mechanisms cited in the literature of migraine and other headache disorders is the activation of nociceptive sensory neurons by cytokines and chemokines. A similar mechanism has been reported in SARS-CoV-2 with the release of cytokines and chemokines by macrophages throughout the course of infection. Other mechanisms for headache in SARS-CoV-2 include (1) viral neuroinvasion as seen with viral encephalitis; (2) hypoxemia due to the well-described pulmonary manifestations of the disease; and (3) thrombosis secondary to COVID-19 induced hypercoagulable states. CONCLUSION: According to the Centers for Disease Control, common symptoms of human coronavirus include fever, cough, runny nose, sore throat, and headache. In the case of SARS-CoV-2, there are limited reports about headaches, one of the most common clinical manifestations. There are currently no studies that focus specifically on headache among patients with SARS-CoV-2 infection.

Headache in Ruptured Intracranial Dermoid Cysts.

PURPOSE OF REVIEW: Intracranial dermoid cysts are benign, rare mass-occupying lesions of the central nervous system arising from the neuroectodermal cell lines. While rupture of intracranial dermoid cysts is rare, it can present with a variety of clinical manifestations. To explore the headache manifestations among patients with ruptured intracranial dermoid cysts. To our knowledge, limited studies focusing on headache due to the intracranial dermoid cysts rupture have been published to date. A literature review was done through PubMed/Medline. Articles within the past 10 years were reviewed. Articles in languages other than English were excluded. RECENT FINDINGS: Rupture of intracranial dermoid cysts could have various manifestations including headache, seizure, and meningitis. Depending on the location of the cyst, headache secondary to the rupture of the intracranial dermoid cysts could present in different ways. A detailed systematic literature review of headache presentations due to intracranial dermoid cysts rupture is provided.

Neuropathogenesis and Neurologic Manifestations of the Coronaviruses in the Age of Coronavirus Disease 2019: A Review.

Importance: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019, causing human coronavirus disease 2019 (COVID-19), which has now spread into a worldwide pandemic. The pulmonary manifestations of COVID-19 have been well described in the literature. Two similar human coronaviruses that cause Middle East respiratory syndrome (MERS-CoV) and severe acute respiratory syndrome (SARS-CoV-1) are known to cause disease in the central and peripheral nervous systems. Emerging evidence suggests COVID-19 has neurologic consequences as well. Observations: This review serves to summarize available information regarding coronaviruses in the nervous system, identify the potential tissue targets and routes of entry of SARS-CoV-2 into the central nervous system, and describe the range of clinical neurological complications that have been reported thus far in COVID-19 and their potential pathogenesis. Viral neuroinvasion may be achieved by several routes, including transsynaptic transfer across infected neurons, entry via the olfactory nerve, infection of vascular endothelium, or leukocyte migration across the blood-brain barrier. The most common neurologic complaints in COVID-19 are anosmia, ageusia, and headache, but other diseases, such as stroke, impairment of consciousness, seizure, and encephalopathy, have also been reported. Conclusions and Relevance: Recognition and understanding of the range of neurological disorders associated with COVID-19 may lead to improved clinical outcomes and better treatment algorithms. Further neuropathological studies will be crucial to understanding the pathogenesis of the disease in the central nervous system, and longitudinal neurologic and cognitive assessment of individuals after recovery from COVID-19 will be crucial to understand the natural history of COVID-19 in the central nervous system and monitor for any long-term neurologic sequelae.

Hemicrania Continua: a Clinical Perspective on Diagnosis and Management.

PURPOSE OF REVIEW: Hemicrania Continua (HC) is a daily and persistent form of headache that is characterized by side-locked pain which is continuous, varies in severity and can be associated with conjunctival injection, lacrimation, nasal congestion, rhinorrhea, eyelid edema, forehead or facial sweating and miosis and/or ptosis. RECENT FINDINGS: Functional imaging studies have shown activation of subcortical structures such as the posterior hypothalamus and dorsal rostral pons, which are known to disinhibit the trigeminal autonomic reflex, a reflex responsible for autonomic outflow through trigeminal efferents. A similar pathway activation is seen in other Trigeminal autonomic cephalalgias (TAC) which solidifies HC as a TAC. While we also discuss promising treatments in our review, more evidence is needed before making them a standard of therapy for HC. This article aims to review the recent research on the diagnosis and clinical management of this potentially underdiagnosed primary headache disorder.

Appropriate use of neuroimaging in headache.

Headache may be caused by primary disorders, such as migraines, or secondary disorders, such as intracranial neoplasm or hemorrhage. Imaging plays an important role in differentiating between primary and secondary headache disorders. This article reviews the effectiveness of computed tomography (CT) and magnetic resonance imaging (MRI) in the evaluation of a patient with a headache. It also discusses the utility and cost-effectiveness of performing imaging studies in patients with a headache and a normal neurological exam. Emerging imaging techniques such as functional MRI, positron emission tomography (PET) scans, and voxel-based morphometry (VBM) are also discussed.