Chiang, Chia‐Chun

Background: Patients with cerebral or spinal cavernous malformations (CM) and a primary headache disorder are often limited in medication options due to concern for bleeding risk. Methods: From a prospective cohort of CM patients (2015–2020), demographics, mode of clinical presentation, and radiographic data were collected. Follow up of patients was performed with electronic medical record review, in person visits and/or written surveys. Select medication use was ascertained from the time of the CM diagnosis to a censor date of first prospective symptomatic hemorrhage, complete surgical excision of sporadic form CM, or death. The influence of non-aspirin NSAID (NA-NSAID), triptan, or OnabotulinumtoxinA on prospective hemorrhage risk was assessed. Results: As of August 20, 2020, 329 patients with spinal or cerebral CM (58% female; 20.1% familial; 42.2% initial presentation due to hemorrhage; 27.4% brainstem) were included. During a follow-up of 1799.9 patient years, 92 prospective hemorrhages occurred. Use of NA-NSAIDs, triptans, and OnabotulinumtoxinA after the diagnosis of CM was unassociated with an increased risk of prospective hemorrhage. Conclusions: Use of triptans and NA-NSAIDs, does not precipitate CM hemorrhage. Similarly, we did not find that OnabotulinumtoxinA precipitated CM hemorrhage in a limited number of patients at doses <200 units per session.

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.

Introduction: Baseline thrombocytopenia (TP) is a common condition in patients with acute coronary syndrome (ACS) and acute ischemic stroke and has been shown to increase mortality. The effect of baseline TP on cerebrovascular events following initial ACS event is not well studied. Methods: We retrospectively reviewed all patients identified from the institutional NCDR Chest Pain registry database at Mayo Clinic Arizona from Oct 2015 to Sep 2018. Patients were classified into TP (platelet <150) and control (platelet > 150) groups for clinical outcome (stroke/TIA and bleeding events) analysis. P-value < 0.05 is considered significant. Results: Five hundred and thirty-six patients were included for final analysis. Patient demographics and clinical outcomes are shown in Table 1. The rates of dual antiplatelet therapy (DAPT) prescription at discharge (TP vs. control: 68.1% and 75.4%, P=0.197), stroke/TIA (1.3% vs. 2.4%, P=1.000) and recurrent myocardial infarction (11.1% vs. 11.2%, P=1.000) were similar between the two groups. The TP group has more bleeding events compared to control (Figure 1). Conclusions: In patients with ACS, baseline TP does not affect stroke/TIA events but is associated with higher bleeding rate. The results could not be explained by the DAPT or anticoagulation use alone. Further studies are needed to investigate the pathophysiologic correlation of thrombocytopenia, DAPT, and stroke in ACS patients.

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.

Background: Left atrial appendage occlusion (LAAO) devices have successfully provided an alternative therapeutic option in patients with atrial fibrillation and high bleeding risk. However, patients with thrombocytopenia (TP) were underrepresented in the milestone trials, and the optimal strategy of postprocedural antithrombotic therapy in this group of patients remains unclear. Methods: Patients were identified from the National Cardiac Database Registry - LAAO database at all three Mayo Clinic sites in the period from 1/2016-10/2019. Patients were further divided into TP (platelet &lt; 150 x 10^9/L) and control (platelet &gt; 150 x 10^9 /L) groups for clinical outcome analysis. Outcome endpoints include composite of bleeding (GI bleeding, hemorrhagic stroke, and other non-intracranial hemorrhage) and composite thrombotic events (device thrombus, ischemic stroke, TIA and undetermined stroke). Results: A total of 249 consecutive patients were included in the final analysis. The mean age was 76.7 ± 7.2 years, and 169 (67.9%) were male; 242 (97.2%) were white. The mean CHA2DS2-VASc score was 5.3 ±1.5, and the HAS-BLED score was 3.0 ± 1.1. TP at baseline was present in 74 (29.7%) patients. The median follow-up time was 6.8 months. The use of post-procedural antithrombotic regimens was similar between the two groups (Table 1). When comparing the TP group to control, there was no significant difference in composite bleeding events (10.8% vs. 8.0%, P = 0.069) and thrombotic events (2.7% vs. 2.3%, P= 0.170). Conclusions: The presence of baseline TP does not significantly increase post-procedural bleeding risk in atrial fibrillation/atrial flutter patients who underwent an LAAO occlusion procedure with the Watchman device (Boston Scientific). This group of patients can be treated with the same antithrombotic regimen as patients with normal platelet levels. Future studies are still warranted to determine the optimal antithrombotic regimen.

Introduction: Respect for patient autonomy is critical, and patients/surrogates may have various preferences about acute stroke treatment that are not fully appreciated during a stroke code. COAST (Coordinating Options for Acute Stroke Therapy) is a stroke advance directive formalizing advanced consent for thrombolysis (tPA) and endovascular therapy (EVT). We examine the distribution of patient preferences to improve understanding and respect for patient autonomy in acute stroke. Methods: In our IRB-approved study, we collected COAST forms at UC San Diego from 12/1/2014-2/29/2020. Patients chose one of five tPA preferences: not under any circumstance (tPA 1); up to 3 hours only, based on FDA approval (tPA 2); up to 4.5 hours only, based on current guidelines (tPA 3); anytime per provider discretion (tPA 4); or other answer (tPA treatment under specific conditions written by the patient/surrogate) (tPA 5). Patients also chose one of five EVT preferences: not under any circumstance (EVT 1); up to 6 hours only (EVT 2); up to 12 hours only (EVT 3); up to 24 hours only (this option replaced "up to 12 hours only" on 3/1/2018 when the 6-24 hour window became standard of care) (EVT 4); anytime at provider discretion (EVT 5); or other answer (EVT treatment under specific conditions written by the patient/surrogate) (EVT 6). Frequency of preferences was calculated for each option. Results: In total, 342 COASTs were completed. Frequency of tPA preferences were: 3.2% for tPA 1 (11/342), 1.5% for tPA 2 (5/342), 25.7% for tPA 3 (88/342), 55.6% for tPA 4 (190/342), 14.0% for tPA 5 (48/342). Frequency of EVT preferences were: 1.8% for EVT 1 (6/342), 9.6% for EVT 2 (33/342), 3.2% for EVT 3 (11/342), 10.8% for EVT 4 (37/342), 62.3% for EVT 5 (213/342), 12.3% for EVT 6 (42/342). When the 6-24 hour window became standard of care, 0% (0/342) chose EVT 2. Total 81.6% (n=279) of COASTs had the same tPA and EVT preferences, and 18.4% (n=63) had tPA preferences that were different from EVT preferences. Conclusion: Preferences vary regarding tPA and EVT treatment. Most patients defer to provider discretion, though some patients have preferences that are different from current provider expectations and/or stroke guidelines. COAST is pivotal to inform respect for patient autonomy for acute stroke codes.

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.