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American Headache Society Annual Meeting

Access daily, concise peer-reviewed reports from the American Headache Society Annual Meeting selected by the Neurology Today editors.

Wednesday, June 9, 2021

Migraine patients taking atogepant, an oral calcitonin gene-related peptide (CGRP) receptor antagonist, reported improvements in their quality of life, according to 12-week, phase 3 data presented  at the virtual American Headache Society Annual Scientific Meeting.

The patients reported improvements early in the treatment period on measures assessing how much their social and work activities are limited by migraine, showing the real-world impact of the therapy, researchers said.

These quality-of-life measures are important because they are “designed to measure a patient's ability to function in everyday life," said Richard B. Lipton, MD, FAAN, director of the Montefiore Headache Center, who presented the findings.

“They are not as important as the primary endpoint in a regulatory sense, but they may be even more important in terms of measuring the most meaningful benefits of treatment.  The good news is that primary efficacy measures and the patient reported outcomes tell a consistent story about efficacy."

The findings come from an analysis of secondary and exploratory endpoints in the ADVANCE trial for prevention of migraine. Researchers looked at measures on the Migraine-Specific Quality of Life Questionnaire (MSQ v2.1), a 14-item questionnaire. In the trial, patients were randomized to receive each day a placebo or atogepant at 10 mg , 30 mg, or 60 mg.

On the MSQ -Role Function-Restrictive portion of the questionnaire—which measures the degree to which migraine limits patients' ability to do social and work activities—all of the atogepant groups had significant improvements in scores. By week 12, the treatment groups' scores had all improved by an average of about 30 points on the questionnaire, about 50 percent better than the placebo group (p<0.0001 for all). This level of difference was seen even at the earliest time point measured, at four weeks.

On the MSQ-Role Function-Preventive portion—which measures how much patient daily social and work activities were interrupted or even prevented due to migraine—the difference wasn't as great, but was still significant. At week 12, the atogepant group scores in this domain had improved by about 20 points, while the placebo group had improved by about 15, with some slight variation between the treatment groups: p=0.0037 for the 10 mg group; p=0.0004 for the 30 mg group; and p=0.0003 for the 60 mg group).

Researchers also looked at emotional function due to migraine, with improvements ranging from 25 to 30 points for the treatment groups, and just over 15 points for the placebo group (p=0.009 for the 10 mg group and p<0.0001 for the 30 mg and 60 mg groups).

Researchers noted that many patients in the placebo group were considered “responders" on the quality-of-life measures, scoring above a pre-determined threshold, but the responder rate for the treatment groups was still significantly better.

Melissa Rayhill, MD, clinical assistant professor of neurology at the University of Buffalo Jacobs School of Medicine and Biomedical Sciences, said the findings show that treatment can have a real-life effect on patients' lives.

“The findings generally showed improvement in patient-reported limitations on work and social life due to migraine at four weeks and was sustained through 12 weeks," she said. “These findings suggest a meaningful improvement in function for patients with migraine, which is an incredibly important outcome to measure. Typically, we counsel patients to expect a change in headache pattern after two to three months of preventive treatment. It would be nice if we can offer patients preventive therapies that may impact headache patterns more quickly, optimizing function without having to wait as long."

Disclosures

Dr. Rayhill did not report any disclosures. ​

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AHS Abstract P-51: Lipton RB, Pozo-Rosich P, Blumenfeld AM, et al. Atogepant improved patient-reported migraine-specific quality of life in a 12-week phase 3 (ADVANCE) trial for preventive treatment of migraine.

Wednesday, June 9, 2021

An artificial intelligence (AI) algorithm using unstructured data in a doctor's notes was more adept at identifying patients with migraine and headache than a traditional method analyzing standard electronic health record (EHR) data, according to findings of an observational pilot study presented here at the virtual American Headache Society Annual Scientific Meeting.

Researchers used traditional extraction techniques—culling information such as medication lists and ICD codes—to pull “structured" data from an EHR system. The AI “unstructured" method processes the natural language in the notes from physicians to retrieve data. The goal was to identify migraine and headache among the patient records assessed, as well as migraine-related symptoms and migraine medications.

 “Algorithms using artificial intelligence applied to EHR unstructured data in our study accurately identified patients with migraine, migraine-related symptoms and migraine medications," reported Daniel Riskin, MD, FACS, and colleagues of Verantos, Inc. “The AI algorithm had consistently higher accuracy than structured data in identifying migraine and migraine-related symptoms. We've recommended further study to develop high validity real-world evidence in migraine."

The structured method identified migraine and headache 30.2 percent of the time compared with 63.3 percent using the AI method. The structured approach also identified migraine-related symptoms in 71.5 percent of the cases, while the AI approach did so 88.8 percent of the time, the investigators reported.

The investigators also pointed out that the structured method had surprisingly low accuracy, particularly when it came to finding conditions of headache and migraine, which could hinder its use in research.

Researchers said the findings from the study suggest that AI could play a larger role in gathering important data in the future, enabling better decision-making. Real-world data collected in clinical care can deepen the understanding of interventions and outcomes than that based only on clinical trial data. And as regulators and payers look to use real-world data more often, they say, better ways of collecting these data are needed.

Stephen Kymes, PhD, MHA, a director with the pharmaceutical company Lundbeck, which helped perform the study, said the approach is worth pursuing further. The AI method provides a more reliable, more robust way to get data, if only the method can be honed and implemented, he said.

Frederick Freitag, DO, professor of neurology at the Medical College of Wisconsin, who was not involved with the study, said he would need more information, including a more detailed description of both techniques, to fully assess them.

Speaking generally, he said, "I have no doubt from other articles I have read and reviewed that there is much to be gained by use AI in patient care. Unfortunately, as a practical application in everyday practice, I can't see it."

Disclosure

Dr. Frietag disclosed receiving speakers honoraria from Lundbeck, AbbVie, and Eli Lilly. 

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AHS Abstract P-33: Riskin D, Cady R, Shroff A, et al. Identification of patients with migraine, migraine-related symptoms and migraine medication use within electronic medical records using artificial intelligence. 


Wednesday, June 9, 2021

Individuals who complain of both temporomandibular disorders and primary headaches are likely to fit the diagnostic criteria for headache attributable to temporomandibular disorder (HATMD), researchers reported at the virtual American Headache Society annual scientific meeting.

In a multivariate analysis, the researchers identified headache frequency, muscle pain, and the most important predictors of HATMD. Monthly headache frequency in the three months prior to enrollment in the study was associated with a 49 percent increased risk for HATMD. Masticatory facial pain nearly tripled the risk of being identified as having HATMD, the researchers reported.

“A better understanding of HATMD is necessary for developing targeted strategies for its therapy," said Inna Tchivileva, MD, assistant professor of medicine at the Adams School of Dentistry of University of North Carolina at Chapel Hill, in her poster presentation.

“I believe that all headache patients should be evaluated for temporomandibular disorders for the differential diagnosis," Dr. Tchivileva told Neurology Today At the Meetings.

Of 185 volunteers who agreed to participate in a cross-sectional study, 62 percent of the group fit the criteria for primary headache as well as HATMD, reported

Eighty percent of the study participants were women. Participants were in their mid-30s, on average, and had been affected by the HATMD for about 10 years.

Ninety-nine individuals also met the criteria for having tension type headache, 87  patients had migraine or possible migraine, and about 54 percent of them met the criteria for HATMD.

Of the 71 patients who had primary headache only, 45 had tension-type headaches and 26 had migraine. Among the patients who fit the diagnostic criteria for HATMD, 53 were also found to have tension-type headaches and 61 patients also had migraine headaches.

Katherine Hamilton, MD, assistant professor of clinical neurology at the University of Pennsylvania, told Neurology Today At the Meetings, “I find that patients I see for headache frequently have temporomandibular disorders, and I refer many of my patients to physical therapy for that condition."

“Sometimes temporomandibular disorder is the primary cause of headaches, especially when the headaches are more tension-type in nature," Dr. Hamilton, who was not involved with the study, said. “But I find that more commonly, temporomandibular disorders occur concurrently with migraine, which can make it more difficult to identify."

“This study shows that temporomandibular disorder is very common among people with primary headache, particularly those with migraine, and contributes to increased frequency and impact of headaches. An important conclusion to be drawn from this study is that failure to diagnose and properly address temporomandibular disorders in patients with primary headache may lead to refractory headaches and suboptimal care," she added.

Disclosures

Dr. Tchivileva disclosed no relationships with industry. Dr. Hamilton disclosed relationships with Guidepoint, Biohaven, and Impel.

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AHS P-23: Tchivileva IE, Ohrbach R, Fillingim RB, et al. Clinical, psychological, and sensory characteristics associated with headache attributable to te​mporomandibular disorder in participants with chronic myofascial temporomandibular disorder. 


Wednesday, June 9, 2021

A number of patients diagnosed with COVID-19 infection also had headaches caused by underlying cerebral venous thrombosis (CVT), researchers reported during the American Headache Society virtual annual scientific meeting. 

Four of the 20 cases identified by an international consortium died and one patient was transferred to a hospital for rehabilitation, said the lead researcher, Mohammed Wasay, MD, professor of neurology at Aga Khan University in Karachi, Pakistan.

However, Dr. Wasay said that the other patients recovered well, with an average discharge score of 1.3 on the modified Rankin Scale.

“COVID-19 increases the propensity for systemic hypercoagulability and thromboembolism," he said. “An association with cerebrovascular diseases, especially cerebral venous thrombosis, has been reported among these patients."

“Cerebral venous thrombosis should be suspected in COVID-19 patients presenting with headache or seizures," Dr. Wasay said. “Mortality is high, but the functional neurological outcome is good among survivors."

The patients in the study were identified from 10 centers in Pakistan, Egypt, Singapore, and the United Arab Emirates. Dr. Wasay said 14 of the patients were men, and the average age of the group as a whole was 42.4 years.

He and his colleagues attempted to determine if there were identifiable risk factors for patients who developed cerebral venous thrombosis in connection with exposure to COVID-19.

Eighty-five percent of the patients in the study reported a headache, and 65 percent had seizures upon presentation, with a mean admission Glasgow Coma Scale score of 13. CVT was the presenting feature in 13 cases, while seven patients developed cerebral venous thrombosis while being treated for COVID-19 infection.

Dr. Wasay said respiratory symptoms were absent in 45 percent of the patients. The most common imaging finding was infarction in 13 patients; hemorrhage occurred in four patients. The superior sagittal sinus was the most common site of thrombosis in 13 patients. Acute inflammatory markers were raised, including elevated serum D-dimer in 17 of the patients, erythrocyte sedimentation rate and C-reactive protein levels. Homocysteine was elevated in half of the tested cases.

He suggested that the mechanism of CVT is likely associated with the known ability of SARS-CoV-2 to bind to angiotensin-converting enzyme-2 receptors, which are variably present in the arterial and venous vascular endothelium.

“COVID-19 not only causes direct vascular damage but may also create an intense inflammatory reaction affecting hemostasis and the coagulation cascade," he said. “COVID-19-associated arterial stroke predominantly affects younger males with vascular risk factors and mostly presents as large vessel stroke. These findings may suggest a common pathway for both COVID-19-associated CVT and arterial stroke."

Dr. Wasay acknowledged that the study was limited by selection bias, the absence of a control sample and a prothrombotic workup, limited neurological examination, and the inability to examine the influence of confounding variables on outcomes.

“The current number of CVT cases is probably an underestimation," he suggested. “COVID-19 testing may be included as standard workup among all CVT patients, including those who have no throat or respiratory symptoms. All COVID-19-positive patients with headache and neurologic symptoms should be evaluated for cerebral venous thrombosis. Early diagnosis by MRI and anticoagulation for high-risk populations may lead to improved outcomes."

In commenting on the study, Noah Rosen, MD, director of Northwell Health's Headache Center in Great Neck, NY, said the findings—although from a small sample and preliminary— should alert clinicians to be aware of the connection between COVID-19 and headaches that may be caused by CVT in this younger age population.

Dr. Rosen noted that as a case series the study has limitations. “It doesn't really tell us the frequency of these cases and whether it is greater than in the general population," he told Neurology Today At the Meetings. “This is more a descriptor of what these researchers saw across all these cases."

He said that headache specialists often see CVT among patients who have hypercoagulative states. “It is relatively infrequent when compared with other headache conditions but it is well-described as a cause of headaches," Dr. Rosen said.

“This is not a definitive study, but it does raise the question of whether we should be looking for more of these cases in the year of COVID-19," he said.

Disclosures

Dr. Wasay disclosed no industry relationships. Dr. Rosen disclosed relationships with Alder, AbbVie, Amgen, Biohaven, Eli Lilly, Lundbeck, and Teva.

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AHS Abstract P-55: Shaikh S, Wasay M. Cerebral venous thrombosis (CVT) associated with COVID-19 infection: A multi-center study.


Tuesday, June 8, 2021

A slight majority of medical education professionals indicated that institutions adequately prepare students to handle the huge volume of patients with headache complaints, researchers reported at the virtual American Headache Society annual scientific meeting.

In a survey of 249 neurology clerkship directors, curriculum deans, or those who held similar positions at all US and Canadian medical schools, 55.1 percent of 78 respondents said that medical students were learning enough about headache medicine at their institution, reported Anna Pace, MD, assistant professor of neurology at the Icahn School of Medicine at Mount Sinai in New York City.

Dr. Pace said 84.6 percent of the responders reported that their institution offered at least one mandatory session on headache, and 65.4 percent felt the preclinical headache curriculum prepares their students for the clinical years.

Respondents suggested that common barriers to educating medical students about headache included insufficient time, lack of administrative support in curricula development, lack of available resources, and lack of student interest. They also suggested that case-based learning modules and online lectures were the most desired materials to improve headache education.

“While most medical schools have at least one lecture on headache medicine, what is taught is inconsistent," Dr. Pace said. “There is a disparity in the number of clinicians trained to treat patients with headache disorders," she said. “Early education and exposure to headache medicine is crucial to address this disparity."

“Migraine ranks as second in the most disabling medical conditions based on disability-adjusted life years," Dr. Pace told Neurology Today at the Meetings. “Despite its prevalence, migraine is often misdiagnosed and managed suboptimally."

One reason for this, she suggested, is that there “are only 707 board-certified headache medicine specialists in the US currently, so there is a significant gap between the number of providers specially trained to treat patients with migraine and other headache syndromes, and the number of people with these conditions."

“Early exposure in medical school and proper instruction of students early on can really help to recruit more providers to the field but also prepare those who pursue other specialties to be able to manage these headache syndromes," Dr. Pace said.

“Regardless of specialty, all physicians will see and interact with patients with headache, and improving headache medicine education at the medical school level will help to improve patient care," she said.

Commenting on the poster, Jessica Ailani, MD, director of the Medstar Georgetown Headache Center and professor of clinical neurology at Medstar Georgetown University Hospital, said the report was generalizable to most institutions.  

“I tell every medical student I train that regardless of what field you go into, a basic understanding of headache disorders is needed—even just the recognition of red flags and when to refer a patient to a specialist, as there is no field of medicine that does not see patients without headaches."

She noted that “the typical person with migraine will often see a primary care provider, an ophthalmologist or optometrist, an ear nose and throat specialist, and then a neurologist. Some women will even consult with their gynecologist before seeing a neurologist." 

“Currently, there is a shortage of neurologists, so training primary care providers to identify and treat headache disorders is critical," Dr. Ailani said.

Dr. Pace reported no relevant financial disclosures. Dr. Ailani has received  consulting fees from Amgen, Abbvie, Biohaven, Axsome, Aeon, Eli Lilly and Company, GlaxoSmithKline, Lundbeck, Teva, Impel, Satsuma, Theranica. She serves on the speakers' bureau for Allergan/Abbvie, Amgen, Biohaven, Eli Lilly and Company, Lundbeck, and Teva; she has received clinical trial grants (to her institution) from the American Migraine Foundation, Allergan/Abbvie, Biohaven, Eli Lilly and Company, Satsuma, and Zosano.

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AHS Abstract P-61: Pace A, Orr SL, Rosen NL, et al. The state of headache medicine education in North America: An observational survey-based study of neurology clerkship directors and curriculum deans.