Chiang, Chia-Chun

Background Headache in patients with moyamoya disease is an under-addressed topic in the medical literature. Delay in the diagnosis of moyamoya disease or inappropriate treatment of headache could lead to devastating cerebrovascular outcome. With the evolving understanding of moyamoya disease, migraine pathophysiology, and various migraine-specific medications that have become available, it is crucial to provide an updated overview on this topic. Methods We searched PubMed for keywords including moyamoya disease, moyamoya syndrome, headache in moyamoya, surgical revascularization, surgical bypass, migraine and moyamoya, and calcitonin gene-related peptide (CGRP). We summarized the literature and provide a comprehensive review of the headache presentation, possible mechanisms, the impact of various surgical revascularizations on headache in patients with moyamoya disease, and the medical management of headache incorporating novel migraine-specific treatments. Results and conclusion: The most common headache phenotype is migraine; tension-type headache, hemiplegic migraine, and cluster headache have also been reported. Most patients experience improvement of headache after surgical revascularization, though some patients report worsening, or new-onset headache after surgery. Given the complexity of moyamoya disease, careful consideration of different types of medical therapy for headache is necessary to improve the quality of life while not increasing the risk of adverse cerebrovascular events. More prospective studies are warranted to better understand and manage headache in patients with moyamoya disease.

Background Retinal migraine is defined by fully reversible monocular visual phenomena. We present two cases that were complicated by permanent monocular vision deficits. Cases A 57-year-old man with history of retinal migraine experienced persistent monocular vision loss after one stereotypical retinal migraine, progressing to finger-count vision over 4 days. He developed paracentral acute middle maculopathy that progressed to central retinal artery occlusion. A 27-year-old man with history of retinal migraine presented with persistent right eye superotemporal scotoma after a retinal migraine. Relative afferent pupillary defect and superotemporal visual field defect were noted, consistent with ischemic optic neuropathy. Conclusion Retinal migraine can complicate with permanent monocular visual loss, suggesting potential migrainous infarction of the retina or optic nerve. A thorough cerebrovascular evaluation must be completed, which was unrevealing in our cases. Acute and preventive migraine therapy may be considered in retinal migraine patients, to mitigate rare but potentially permanent visual loss.

Abstract Objective We sought to investigate the patient experience of telemedicine for headache care during the coronavirus disease 2019 (COVID‐19) pandemic. Background The use of telemedicine has rapidly expanded and evolved since the beginning of the COVID‐19 pandemic. Telemedicine eliminates the physical and geographic barriers to health care, preserves personal protective equipment, and prevents the spread of COVID‐19 by allowing encounters to happen in a socially distanced way. However, few studies have assessed the patient perspective of telemedicine for headache care. Methods The American Migraine Foundation (AMF) designed a standardized electronic questionnaire to assess the patient experience of telemedicine for headache care between March and September 2020 to help inform future quality improvement as part of its patient advocacy initiative. The date parameters were identified as the emergence of severe acute respiratory syndrome coronavirus 2 disease and the declaration of a national emergency in the United States. The questionnaire was distributed electronically to more than 100,000 members of the AMF community through social media platforms and the AMF email database. Results A total of 1172 patients responded to our electronic questionnaire, with 1098 complete responses. The majority, 1081/1153 (93.8%) patients, had a previous headache diagnosis prior to the telemedicine encounter. A total of 648/1127 (57.5%) patients reported that they had used telemedicine for headache care during the study period. Among those who participated in telehealth visits, 553/647 (85.5%) patients used it for follow‐up visits; 94/647 (14.5%) patients used it for new patient visits. During the telemedicine encounters, 282/645 (43.7%) patients were evaluated by headache specialists, 222/645 (34.4%) patients by general neurologists, 198/645 (30.7%) patients by primary care providers, 73/645 (11.3%) patients by headache nurse practitioners, and 21/645 (3.2%) patients by headache nurses. Only 47/633 (7.4%) patients received a new headache diagnosis from telemedicine evaluation, whereas the other 586/633 (92.6%) patients did not have a change in their diagnoses. During these visits, a new treatment was prescribed for 358/636 (52.3%) patients, whereas 278/636 (43.7%) patients did not have changes made to their treatment plan. The number (%) of patients who rated the telemedicine headache care experience as “very good,” “good,” “fair,” “poor,” and “other” were 396/638 (62.1%), 132/638 (20.7%), 67/638 (10.5%), 23/638 (3.6%), and 20/638 (3.1%), respectively. Detailed reasons for “other” are listed in the manuscript. Most patients, 573/638 (89.8%), indicated that they would prefer to continue to use telemedicine for their headache care, 45/638 (7.1%) patients would not, and 20/638 (3.1%) patients were unsure. Conclusions Our study evaluating the patient perspective demonstrated that telemedicine facilitated headache care for many patients during the COVID‐19 pandemic, resulting in high patient satisfaction rates, and a desire to continue to use telemedicine for future headache care among those who completed the online survey.

Abstract Objective To assess the real‐world efficacy, tolerability, and safety of ubrogepant in a tertiary headache center. Background The efficacy and safety of ubrogepant for the acute treatment of migraine were established in phase 3 randomized controlled trials. However, there is no real‐world data of patient experience with ubrogepant in a population in which the majority of patients have chronic migraine, multiple prior unsuccessful treatments, complex medical comorbidities, and concurrent use of other migraine‐specific medications. Method This was a post‐market cohort study conducted at Mayo Clinic Arizona. All patients prescribed ubrogepant were tracked and contacted 1–3 months after the prescription to answer a list of standardized questions. Demographic information and additional headache history were obtained from chart review. Results We obtained eligible questionnaire responses from 106 patients. Chronic migraine accounted for 92/106 (86.8%) of the population. Complete headache freedom (from mild/moderate/severe to no pain) and headache relief (from moderate/severe to mild/no pain or mild to no pain) for ≥75% of all treated attacks at 2 hours after taking ubrogepant were achieved in 20/105 (19.0%) and 50/105 (47.6%) patients, respectively. A total of 33/106 (31.1%) patients reported being “very satisfied” with ubrogepant. Adverse events were reported in 42/106 (39.6%) patients, including fatigue in 29/106 (27.4%), dry mouth in 8/106 (7.5%), nausea/vomiting in 7/106 (6.6%), constipation in 5/106 (4.7%), dizziness in 3/106 (2.8%), and other adverse events in 7/106 (6.6%). Predictive factors for being a “good responder” to ubrogepant, defined as headache relief for ≥75% of all treated attacks at 2 hours after taking ubrogepant, included migraine with aura, episodic migraine, <5 prior unsuccessful preventive or acute treatment trials. Additionally, prior treatment responses to a CGRP monoclonal antibody and onabotulinumtoxinA injections are predictive of treatment responses and patient satisfaction to ubrogepant. For the 62/106 (58.5%) patients concurrently using a CGRP monoclonal antibody, there was no difference in the “good responder” rate or adverse event rate compared to those who were not on a CGRP monoclonal antibody, though the rate of moderate, as opposed to mild adverse events was higher, 11/62 (47.8%) versus 3/44 (17.6%), p = 0.048. Additionally, 16 patients had a history of significant cardiovascular or cerebrovascular diseases. No severe adverse events were reported in any patient. Conclusion Our study confirms and extends the efficacy profile and tolerability of ubrogepant in a real‐world tertiary headache clinic and identifies factors that may predict efficacy. Adverse event rates were higher than reported in clinical trials. Further studies are needed to confirm these findings and to evaluate the long‐term efficacy and safety of ubrogepant.

Objective To summarize the current literature on non‐steroidal anti‐inflammatory drug and corticosteroid use during the coronavirus disease 2019 (COVID‐19) pandemic, recognizing that these are commonly used treatments in the field of headache medicine. Background The use of non‐steroidal anti‐inflammatory drugs and corticosteroids in patients during the COVID‐19 pandemic has been a controversial topic within the medical community and international and national health organizations. Lay press and social media outlets have circulated opinions on this topic despite the fact that the evidence for or against the use of these medications is sparse. In the field of headache medicine, these medications are used commonly and both patients and clinicians may have questions or hesitations pertaining to their use during the COVID‐19 pandemic. Methods A detailed search of the scientific and popular literature was performed. Results There is limited literature pertaining to the safety of non‐steroidal anti‐inflammatory drugs and corticosteroids during the COVID‐19 pandemic. To date, there are no clear scientific data that preclude the use of non‐steroidal anti‐inflammatory drugs in the general population who may acquire COVID‐19 or in those acutely infected with the virus. Several health organizations have concluded that treatment with corticosteroids during active infection should be avoided due to concerns of prolonged viral shedding in the respiratory tract and the lack of survival benefit based on the data from past coronaviruses and influenza virus; specific exceptions exist including treatment for underlying asthma or chronic obstructive pulmonary disease, septic shock, and acute respiratory distress syndrome. Conclusion Scientific information regarding the COVID‐19 pandemic is constantly evolving, and limited or contradictory information can lead to confusion for both patients and clinicians. It is recommended that prior to prescribing non‐steroidal anti‐inflammatory drugs and steroids for the treatment of headache, clinicians have open discussions with their patients about the potential risks and benefits of using these medications during the COVID‐19 pandemic. This manuscript summarizes the currently available evidence and understanding about these risks and benefits to help clinicians navigate such discussions.

Background The King-Devick test is a timed rapid number naming task that involves complex cerebral functions. The objective of this pilot exploratory study is to determine whether there is a difference in the King-Devick test during a migraine attack compared to the interictal phase. Methods We evaluated 29 adult subjects with migraine with aura or migraine without aura. For each participant, we performed King-Devick tests during migraine attacks and interictal phases. Subjects served as their own controls. Results The King-Devick test was slower during the migraine attack compared to the interictal baseline (median 4.6 sec slower, p < 0.001). The slowing of the King-Devick test during migraine attack was more prominent in those with migraine with aura compared to subjects with migraine without aura (median 7.5 vs. 2.8 sec, p = 0.028). Conclusions This exploratory, observational study shows changes in the King-Devick test during migraine compared to the interictal phase. Future studies are required to determine if the King-Devick test may be used as a rapid and simple tool to objectively characterize migraine-associated disability.

Objective To investigate differences in cortical thickness in patients with persistent post‐traumatic headache (PPTH) relative to healthy controls and to interrogate whether cortical morphology relates to headache burden (headache frequency, years with post‐traumatic headache, PTH) in patients with PPTH. Background PTHs are one of the most common symptoms following concussion. In some patients, PTHs continue for longer than three months and are classified as PPTH. This study has two main goals: (1) To delineate the neuropathology of PPTH, by interrogating differences in cortical thickness in patients with PPTH relative to healthy controls. (2) To interrogate potential associations between brain morphology and headache burden in patients with PPTH by examining whether cortical thickness relates to frequency of headaches or years lived with PTH. Methods Adults with PPTH diagnosed according to ICHD 3 beta diagnostic criteria and healthy controls underwent brain MRI on a 3 Tesla scanner. Vertex‐by‐vertex whole brain estimates of cortical thickness were automatically calculated using FreeSurfer v5.3. Differences in cortical thickness in patients with PPTH relative to healthy controls were determined using a general linear model design. Associations were explored between regional clusters where patients with PPTH showed cortical thickness differences compared with healthy controls with headache frequency and years lived with PPTH. Results This study included 33 patients with PPTH and 33 healthy control subjects (healthy controls: median age = 33.0, IQR = 15.5; patients with PPTH: median age = 36.0, IQR = 20.5; P = .56). Patients with PPTH had less cortical thickness relative to healthy controls in the left and right superior frontal, caudal middle frontal, and precentral cortex as well as less cortical thickness in the right supramarginal, right superior and inferior parietal, and right precuneus region ( P < .05, Monte Carlo corrected for multiple comparisons). There were no regions where patients with PPTH had more cortical thickness relative to healthy controls. A correlation analysis of regions that showed less cortical thickness in patients with PPTH demonstrated a negative correlation between left and right superior frontal thickness with headache frequency ( P < .05). There was no association between regional cortical thickness and years lived with PPTH. Conclusion Compared with healthy controls, patients with PPTH had less cortical thickness in bilateral frontal regions and right hemisphere parietal regions. For patients with PPTH, more frequent headaches were related to less thickness in the left and right superior frontal regions, potentially indicating that brain morphology changes in the superior frontal regions in patients with PPTH are modified by headache frequency.

Chronic migraine is a debilitating neurobiological disorder that affects approximately 1.4–2.2% of the population worldwide. Patients with chronic migraine have 15 or more headache days per month, with at least 8 days per month that meet the criteria for migraine. Injection of onabotulinumtoxinA, using a standardized injection protocol, was approved by the US Food and Drug Administration in 2010 for the treatment of chronic migraine. The approval was made based on results from two large, randomized, double-blind placebo-controlled trials: the Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) trials. Since then, numerous studies have been performed investigating the short-term and long-term benefits, risks and complications of the use of onabotulinumtoxinA injections for the treatment of chronic migraine. The purpose of this narrative review is to describe the currently available clinical evidence for the use of onabotulinumtoxinA injections for treating patients with chronic migraine.

ABSTRACTIntroduction: We describe an unusual case of pleural drop metastases 21 years after complete resection of an encapsulated thymoma in a Southeast Asian patient with myasthenia gravis (MG). Methods: This investigation includes a case report and brief review of the literature. Results: The patient presented in 2015 with generalized weakness, fatigue, and shortness of breath, but no diplopia, ptosis, dysphagia, or dysarthria. Because these symptoms were atypical for an MG exacerbation, a de‐novo work‐up was performed. Chest computed tomography (CT) showed numerous pleural nodules (“drop metastases”), and CT‐guided biopsy revealed metastatic thymoma. Conclusions: The average disease‐free interval for thymoma ranges from 68 to 86 months. Pleural and mediastinal recurrence are more common than distant hematogenous recurrence. Adverse prognostic factors include an initial higher Masaoka stage, incomplete resection, older age, and pleural or pericardial involvement. Despite apparent complete resection of thymoma, clinicians should remain vigilant for recurrence for as long as 20 years after initial management. Long‐term follow‐up with radiologic surveillance is recommended. Muscle Nerve 56: 171–175, 2017