Bio

Clinical Focus


  • Neurology

Academic Appointments


Professional Education


  • Board Certification: United Council for Neurologic Subspecialties, Headache Medicine (2014)
  • Fellowship: Stanford School of Medicine (2014) CA United States of America
  • Residency: University of California at Irvine (2013) CA
  • Internship: University of California at Irvine (2010) CA
  • Medical Education: University of Toledo College of Medicine (2009) OH
  • Board Certification: American Board of Psychiatry and Neurology, Neurology (2013)

Research & Scholarship

Clinical Trials


  • A Study of Galcanezumab in Participants With Chronic Cluster Headache Recruiting

    The main purpose of this study is to evaluate the efficacy of the study drug known as galcanezumab in participants with chronic cluster headache.

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  • A Study Of Galcanezumab In Participants With Episodic Cluster Headache Recruiting

    The main purpose of this study is to evaluate the efficacy and safety of the study drug known as Galcanezumab in participants with episodic cluster headaches.

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  • Non-invasive Vagus Nerve Stimulation for the Prevention of Migraines Recruiting

    The purpose of the study is to investigate if the use of gammaCore Sapphire™ device reduces the number of migraines preventatively.

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  • eNeura SpringTMS Post-Market Observational US Study of Migraine Not Recruiting

    A multi-center, prospective, non-randomized, single arm, open label, post-market, observational study to evaluate the use of the eneura, springtms system in reduction of migraine headache symptoms.

    Stanford is currently not accepting patients for this trial. For more information, please contact Evalina Salas, 650-723-6469.

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  • Study of Sustained Benefit of Erenumab in Adult Episodic Migraine Patients Not Recruiting

    The primary objective is to demonstrate the superiority of subcutaneous erenumab compared to oral prophylactic(s) on sustained benefit defined as % subjects completing one-year on the randomized treatment and achieving at least a 50% reduction from baseline in monthly migraine days at month 12.

    Stanford is currently not accepting patients for this trial.

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Publications

All Publications


  • Eptinezumab for the prevention of chronic migraine: efficacy and safety through 24weeks of treatment in the phase 3 PROMISE-2 (Prevention of migraine via intravenous ALD403 safety and efficacy-2) study. The journal of headache and pain Silberstein, S., Diamond, M., Hindiyeh, N. A., Biondi, D. M., Cady, R., Hirman, J., Allan, B., Pederson, S., Schaeffler, B., Smith, J. 2020; 21 (1): 120

    Abstract

    BACKGROUND: PROMISE-2 was a phase 3, randomized, double-blind, placebo-controlled study that evaluated the efficacy and safety of repeat intravenous (IV) doses of the calcitonin gene-related peptide-targeted monoclonal antibody eptinezumab (ALD403) for migraine prevention in adults with chronic migraine. This report describes the results of PROMISE-2 through 24weeks of treatment.METHODS: Patients received up to two 30-min IV administrations of eptinezumab 100mg, 300mg, or placebo separated by 12weeks. Patients recorded migraine and headache endpoints in a daily eDiary. Additional assessments, including patient-reported outcomes, were performed at regularly scheduled clinic visits throughout the 32-week study period (screening, day 0, and weeks 2, 4, 8, 12, 16, 20, 24, and 32).RESULTS: A total of 1072 adults received treatment: eptinezumab 100mg, n=356; eptinezumab 300mg, n=350; placebo, n=366. The reduction in mean monthly migraine days observed during the first dosing interval (100mg, -7.7days; 300mg, -8.2days; placebo, -5.6days) was further decreased after an additional dose (100mg, -8.2days; 300mg, -8.8days; placebo, -6.2days), with both doses of eptinezumab demonstrating consistently greater reductions from baseline compared to placebo. The ≥50% and≥75% migraine responder rates (MRRs) increased after a second dose, with more eptinezumab-treated patients experiencing migraine response than placebo patients (≥50% MRRs weeks 13-24: 100mg, 61.0%; 300mg, 64.0%; placebo, 44.0%; and≥75% MRRs weeks 13-24: 100mg, 39.3%; 300mg, 43.1%; placebo, 23.8%). The percentages of patients who improved on patient-reported outcomes, including the Headache Impact Test and Patient Global Impression of Change, increased following the second dose administration at week 12, and were greater with eptinezumab than with placebo at all time points. No new safety concerns were identified with the second dose regarding the incidence, nature, and severity of treatment-emergent adverse events.CONCLUSION: Eptinezumab 100mg or 300mg administered IV at day 0 and repeated at week 12 provided sustained migraine preventive benefit over a full 24weeks and demonstrated an acceptable safety profile in patients with chronic migraine.TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT02974153 ). Registered November 23, 2016.

    View details for DOI 10.1186/s10194-020-01186-3

    View details for PubMedID 33023473

  • The Role of Diet and Nutrition in Migraine Triggers and Treatment: A Systematic Literature Review. Headache Hindiyeh, N. A., Zhang, N., Farrar, M., Banerjee, P., Lombard, L., Aurora, S. K. 2020

    Abstract

    BACKGROUND: Migraine is a disabling primary headache disorder often associated with triggers. Diet-related triggers are a common cause of migraine and certain diets have been reported to decrease the frequency of migraine attacks if dietary triggers or patterns are adjusted.OBJECTIVE: The systematic literature review was conducted to qualitatively summarize evidence from the published literature regarding the role of diet patterns, diet-related triggers, and diet interventions in people with migraine.METHODS: A literature search was carried out on diet patterns, diet-related triggers, and diet interventions used to treat and/or prevent migraine attacks, using an a priori protocol. MEDLINE and EMBASE databases were searched to identify studies assessing the effect of diet, food, and nutrition in people with migraine aged ≥18years. Only primary literature sources (randomized controlled trials or observational studies) were included and searches were conducted from January 2000 to March 2019. The NICE checklist was used to assess the quality of the included studies of randomized controlled trials and the Downs and Black checklist was used for the assessment of observational studies.RESULTS: A total of 43 studies were included in this review, of which 11 assessed diet patterns, 12 assessed diet interventions, and 20 assessed diet-related triggers. The overall quality of evidence was low, as most of the (68%) studies assessing diet patterns and diet-related triggers were cross-sectional studies or patient surveys. The studies regarding diet interventions assessed a variety of diets, such as ketogenic diet, elimination diets, and low-fat diets. Alcohol and caffeine uses were the most common diet patterns and diet-related triggers associated with increased frequency of migraine attacks. Most of the diet interventions, such as low-fat and elimination diets, were related to a decrease in the frequency of migraine attacks.CONCLUSIONS: There is limited high-quality randomized controlled trial data on diet patterns or diet-related triggers. A few small randomized controlled trials have assessed diet interventions in preventing migraine attacks without strong results. Although many patients already reported avoiding personal diet-related triggers in their migraine management, high-quality research is needed to confirm the effect of diet in people with migraine.

    View details for DOI 10.1111/head.13836

    View details for PubMedID 32449944

  • Cerebrospinal Fluid Leak in the context of Pars Interarticularis Fracture: A Case Series Chan, L., Cowan, R., Hindiyeh, N., Hashmi, S., Lanzman, B., Carroll, I. LIPPINCOTT WILLIAMS & WILKINS. 2020
  • Patient-Identified Most Bothersome Symptom in Patients with Chronic Migraine: An Analysis of PROMISE-2 Lipton, R. B., Dodick, D. W., Ailani, J., Winner, P., Hindiyeh, N. A., Hirman, J., Snapinn, S., Mehta, L., Cady, R. LIPPINCOTT WILLIAMS & WILKINS. 2020
  • Assessment of immunogenicity from galcanezumab phase 3 trials in patients with episodic or chronic migraine. Cephalalgia : an international journal of headache Martinez, J. M., Hindiyeh, N., Anglin, G., Kalidas, K., Hodsdon, M. E., Kielbasa, W., Moser, B. A., Pearlman, E. M., Garces, S. 2020: 333102420920642

    View details for DOI 10.1177/0333102420920642

    View details for PubMedID 32340471

  • Spinal cerebrospinal fluid leak in the context of pars interarticularis fracture. BMC neurology Chan, T. L., Cowan, R., Hindiyeh, N., Hashmi, S., Lanzman, B., Carroll, I. 2020; 20 (1): 162

    Abstract

    Spinal cerebrospinal fluid (CSF) leak can lead to intracranial hypotension and is an important differential diagnosis to consider in patients with sudden-onset chronic daily headaches. Pars interarticularis (PI) fracture is a potential rare cause of suspected spinal CSF leak.This is a retrospective case series of 6 patients with suspected spinal CSF leak evaluated between January 2016 and September 2019. All patients received a magnetic resonance imaging (MRI) of the brain with and without gadolinium, MRI whole spine and full spine computed tomography (CT) myelogram. Targeted epidural patches with fibrin sealant were performed. Treatment response at return visit (3 months post-patch) was documented.Six patients (4 females, 2 males) were diagnosed with a suspected spinal CSF leak and PI fracture. Mean age at the time of headache onset was 39 years old, and a range from 32 to 50 years old. Mean time to targeted epidural patches with fibrin sealant was 4.5 years. All 6 patients had PI fractures identified on CT myelogram and received targeted epidural patches with fibrin sealant at the site of the PI fracture. All patients had significant improvement in their headache intensity.Our study highlights: 1) the importance of PI fracture as a possible culprit of suspected spinal CSF leak in patients with intracranial hypotension; 2) the added benefit of CT imaging for detecting bony abnormalities such as fractures in patients with intracranial hypotension; and 3) the successful treatment of suspected spinal CSF leak when targeting the fracture site.

    View details for DOI 10.1186/s12883-020-01740-1

    View details for PubMedID 32349710

  • Shift from Chronic to Episodic Migraine Status in a Long-Term Phase 3 Study of Galcanezumab Detke, H. C., Day, K. A., Lipsius, S., Aurora, S. K., Hindiyeh, N. A., Diener, H., Nicholson, R. WILEY. 2019: S245
  • Combined hormonal contraception and migraine: are we being too strict? Current opinion in obstetrics & gynecology Voedisch, A. J., Hindiyeh, N. 2019

    Abstract

    PURPOSE OF REVIEW: Combined hormonal contraception has been contraindicated in migraines, especially in migraines with aura, because of ischemic stroke risk. Newer formulations are now available and physicians may unnecessarily be limiting access to contraceptive and medical therapeutic options for patients with migraines. This review summarizes the available data regarding ischemic stroke risk of modern combined hormonal contraception in the setting of migraines.RECENT FINDINGS: Limited data exists on current formulations of combined hormonal contraception and outcomes in migraine patients. Studies indicate ischemic stroke risk may be estrogen dose related with high dose formulations having the highest risk. Absolute risk of ischemic stroke with combined hormonal contraception and migraines is low.SUMMARY: Ischemic stroke risk in combined hormonal contraception users in the setting of migraines is low and an individual approach may be more appropriate than current guidelines.

    View details for DOI 10.1097/GCO.0000000000000586

    View details for PubMedID 31573998

  • Online Migraine Education and Support for Patients: Perspectives from the American Headache Society Emerging Leaders Program. Headache VanderPluym, J. H., Hamilton, K., Hindiyeh, N. A., Robbins, M. S., Starling, A. J., Vargas, B. B., Gibbons, S. K., Vgontzas, A. 2019

    View details for DOI 10.1111/head.13649

    View details for PubMedID 31508808

  • Efficacy of Qtrypta (zolmitriptan intracutaneous system) Before and After the Initiation of CGRP Antibody Therapy in Subjects with Migraine - a Preliminary Assessment Hindiyeh, N., Schmidt, P., Engels, J., Halladay, W., Kellerman, D. SAGE PUBLICATIONS LTD. 2019: 394
  • Review of Acute Treatment of Migraine Trial Results With the New FDA Endpoints: Design Implications for Future Trials HEADACHE Hindiyeh, N. A., Kellerman, D. J., Schmidt, P. C. 2019; 59 (5): 819–24

    View details for DOI 10.1111/head.13511

    View details for Web of Science ID 000472202500012

  • Review of Acute Treatment of Migraine Trial Results With the New FDA Endpoints: Design Implications for Future Trials. Headache Hindiyeh, N. A., Kellerman, D. J., Schmidt, P. C. 2019

    Abstract

    BACKGROUND: In October 2014, the US Food and Drug Administration released a draft guidance for the development of drugs for the acute treatment of migraine. This guidance offered the option of replacing the previously required 4 co-primary endpoints: pain freedom, freedom from nausea, freedom from photophobia, and freedom from phonophobia, all at 2 hours posttreatment, with 2 co-primary endpoints: pain freedom and freedom from most bothersome symptom (MBS) other than pain, both at 2 hours posttreatment. At the time the new draft guidance was released, no large clinical trials had been undertaken with these 2 co-primary endpoints, posing a challenge in determining the sample size that might be required to achieve statistical significance. As a number of trials have now been completed, we conducted a review of the observed placebo responses, drug effect sizes, and sample sizes to better inform the design of future trials.METHODS: We searched PubMed, Embase, Web of Science, and the Cochrane library for primary publications of phase 3 randomized, placebo-controlled, double-blind acute migraine treatment trials that used pain freedom and MBS freedom as primary or planned secondary endpoints. For each endpoint, placebo response rates were determined and used to generate estimates of sample size, assuming differences between placebo and active treatment groups of 10%, 15%, and 20%. Sample size calculations were based on 80% power using a 2-group continuity corrected chi-square test with a 5% 2-sided significance level.RESULTS: We identified abstracts or full-length papers describing results of 8 clinical trials employing the new co-primary endpoints. The mean placebo response rate for 2-hour pain freedom was 16.75% (range 11.8-21.3%) and treatment effect (difference in response rates between active and placebo groups) ranged from 5.0% to 27.2%. For 2-hour MBS freedom, the mean placebo response rate was 32.8% (range 25.2-48.1%), and the range of treatment effect was 8.9% to 25.4%. Based on a placebo response rate of 17% for pain freedom, the sample sizes that would have been required to achieve statistical significance were n=269, n=128, and n=77, for treatment effect sizes of 10%, 15%, and 20%, respectively. For MBS, assuming a placebo response rate of 33%, the corresponding required sample sizes would have been n=389, n=181, and n=105.CONCLUSIONS: The observed range of placebo response and treatment effect sizes suggests that use of the newly recommended 2 co-primary endpoints could reduce the sample sizes required to achieve significance compared with past trials using 4 primary endpoints (in which mean and median group sizes for recent trials were 375 and 362, respectively). However, the initial trials using the newly recommended co-primary endpoints tended to treat more participants than would have been minimally required. We anticipate that with the growing body of information regarding the use of these new endpoints, samples sizes may be more aligned with treatment efficacy, enabling faster and more cost-effective trials for acute migraine treatment.

    View details for PubMedID 30953576

  • Systematic Review: Acupuncture vs Standard Pharmacological Therapy for Migraine Prevention. Headache Zhang, N., Houle, T., Hindiyeh, N., Aurora, S. K. 2019

    Abstract

    Standard pharmacological treatment of migraine has many shortcomings. Acupuncture is becoming a more widely used therapy for the prevention and treatment of migraine, but its effectiveness is still in question when compared to the pharmacological treatments even though very few of these have Class A and B evidence for migraine prevention. This is a systematic review of data from existing randomized trials that compare the effectiveness of acupuncture treatment with conventional migraine preventative medications.Custom-designed strategy was used for searching Pubmed (includes MEDLINE), Scopus (includes EMBASE). The inclusion criteria were English language and randomized trials. No date restriction was utilized. We included randomized trials and randomized controlled trials in adult patients that compared the clinical effects of acupuncture with a standard migraine preventive medication in patients with a diagnosis of chronic or episodic migraine with or without aura. We excluded letters and studies on acupuncture for headaches other than migraine. Two reviewers checked eligibility; extracted information on patients, interventions, methods, and results; and assessed the quality of the acupuncture intervention based on the American Academy of Neurology Classification of evidence matrix for therapeutic trials. The present review was not registered.Out of the 706 search results, 7 clinical trials, with a total of 1430 participants, met inclusion criteria for trials comparing the effectiveness of acupuncture to standard pharmacologic treatment. Several of the studies showed acupuncture to be more effective than standard pharmacological treatments for migraine prevention; however, methodological heterogeneity precluded aggregation of these data.There is growing evidence that acupuncture is just as effective and has fewer side effects than many of the standard pharmaceutical agents that are currently used. However, the heterogeneity of the existing studies limits the effective comparison and analysis.

    View details for DOI 10.1111/head.13723

    View details for PubMedID 31872864

  • A multicenter, prospective, single arm, open label, observational study of sTMS for migraine prevention (ESPOUSE Study) CEPHALALGIA Starling, A. J., Tepper, S. J., Marmura, M. J., Shamim, E. A., Robbins, M. S., Hindiyeh, N., Charles, A. C., Goadsby, P. J., Lipton, R. B., Silberstein, S. D., Gelfand, A. A., Chiacchierini, R. P., Dodick, D. W. 2018; 38 (6): 1038–48

    Abstract

    Objective To evaluate the efficacy and tolerability of single pulse transcranial magnetic stimulation (sTMS) for the preventive treatment of migraine. Background sTMS was originally developed for the acute treatment of migraine with aura. Open label experience has suggested a preventive benefit. The objective of this trial was to evaluate the efficacy and tolerability of sTMS for migraine prevention. Methods The eNeura SpringTMS Post-Market Observational U.S. Study of Migraine (ESPOUSE) Study was a multicenter, prospective, open label, observational study. From December 2014 to March 2016, patients with migraine (n = 263) were consented to complete a 1-month baseline headache diary followed by 3 months of treatment. The treatment protocol consisted of preventive (four pulses twice daily) and acute (three pulses repeated up to three times for each attack) treatment. Patients reported daily headache status, medication use, and device use with a monthly headache diary. The primary endpoint, mean reduction of headache days compared to baseline, was measured over the 28-day period during weeks 9 to 12. The primary endpoint was compared to a statistically-derived placebo estimate (performance goal). Secondary endpoints included: 50% responder rate, acute headache medication consumption, HIT-6, and mean reduction in total headache days from baseline of any intensity. Results Of a total of 263 consented subjects, 229 completed a baseline diary, and 220 were found to be eligible based on the number of headache days. The device was assigned to 217 subjects (Safety Data Set) and 132 were included in the intention to treat Full Analysis Set. For the primary endpoint, there was a -2.75 ± 0.40 mean reduction of headache days from baseline (9.06 days) compared to the performance goal (-0.63 days) ( p < 0.0001). The 50% responder rate of 46% (95% CI 37%, 56%) was also significantly higher ( p < 0.0001) than the performance goal (20%). There was a reduction of -2.93 (5.24) days of acute medication use, headache impact measured by HIT-6, -3.1 (6.4) ( p < 0.0001), and total headache days of any intensity -3.16 days (5.21) compared to the performance goal (-0.63 days) ( p < 0.0001). The most common adverse events were lightheadedness (3.7%), tingling (3.2%), and tinnitus (3.2%). There were no serious adverse events. Conclusions This open label study suggests that sTMS may be an effective, well-tolerated treatment option for migraine prevention. Trial registration number NCT02357381.

    View details for DOI 10.1177/0333102418762525

    View details for Web of Science ID 000432049800003

    View details for PubMedID 29504483

    View details for PubMedCentralID PMC5944078

  • A Multicenter, Prospective, Single Arm, Open Label, Post-Market, Observational Study to evaluate the use of sTMS in reduction of Migraine Headache (ESPOUSE Study) Starling, A. J., Tepper, S. J., Marmura, M. J., Shamim, E. A., Robbins, M. S., Hindiyeh, N. A., Charles, A. C., Goadsby, P. J., Lipton, R. B., Silberstein, S. D., Dodick, D. W. SAGE PUBLICATIONS LTD. 2017: 115–16
  • Improving the detection of chronic migraine: Development and validation of Identify Chronic Migraine (ID-CM) CEPHALALGIA Lipton, R. B., Serrano, D., Buse, D. C., Pavlovic, J. M., Blumenfeld, A. M., Dodick, D. W., Aurora, S. K., Becker, W. J., Diener, H., Wang, S., Vincent, M. B., Hindiyeh, N. A., Starling, A. J., Gillard, P. J., Varon, S. F., Reed, M. L. 2016; 36 (3): 203-215

    Abstract

    Migraine, particularly chronic migraine (CM), is underdiagnosed and undertreated worldwide. Our objective was to develop and validate a self-administered tool (ID-CM) to identify migraine and CM.ID-CM was developed in four stages. (1) Expert clinicians suggested candidate items from existing instruments and experience (Delphi Panel method). (2) Candidate items were reviewed by people with CM during cognitive debriefing interviews. (3) Items were administered to a Web panel of people with severe headache to assess psychometric properties and refine ID-CM. (4) Classification accuracy was assessed using an ICHD-3β gold-standard clinician diagnosis.Stages 1 and 2 identified 20 items selected for psychometric validation in stage 3 (n = 1562). The 12 psychometrically robust items from stage 3 underwent validity testing in stage 4. A scoring algorithm applied to four symptom items (moderate/severe pain intensity, photophobia, phonophobia, nausea) accurately classified most migraine cases among 111 people (sensitivity = 83.5%, specificity = 88.5%). Augmenting this algorithm with eight items assessing headache frequency, disability, medication use, and planning disruption correctly classified most CM cases (sensitivity = 80.6%, specificity = 88.6%).ID-CM is a simple yet accurate tool that correctly classifies most individuals with migraine and CM. Further testing in other settings will also be valuable.

    View details for DOI 10.1177/0333102415583982

    View details for Web of Science ID 000371311100001

    View details for PubMedID 26002700

    View details for PubMedCentralID PMC4766965

  • What the Gut Can Teach Us About Migraine CURRENT PAIN AND HEADACHE REPORTS Hindiyeh, N., Aurora, S. K. 2015; 19 (7)

    Abstract

    During gestation, cells of the brain and gut develop almost simultaneously into the central nervous system (CNS) and enteric nervous system (ENS), respectively. They remain connected via the vagal nerve lifelong. While it is well known that the brain sends signal to the gut, communication is in fact bidirectional. Just as the brain can modulate gut functioning, the gut, and likely what we ingest, can in fact influence our brain functioning. We will first review both gastrointestinal (GI) function and migraine pathophysiology and then discuss evidence linking the migraine brain to various GI disorders. Lastly, we discuss the effects of gut microbiota on brain functioning and speculate how the gut and particularly diet may affect migraine.

    View details for DOI 10.1007/s11916-015-0501-4

    View details for Web of Science ID 000356254100004

    View details for PubMedID 26049770

  • Does exercise make migraines worse and tension type headaches better? Current pain and headache reports Hindiyeh, N. A., Krusz, J. C., Cowan, R. P. 2013; 17 (12): 380-?

    Abstract

    Many non-pharmacological treatments have been implicated in the treatment of primary headache, with exercise being a common recommendation. In this review we first provide an overview of the relationship between exercise and primary headaches. We then review the physiology of pain modulation, with focus on the endogenous opioids, endocannabinoids, and neuropeptides calcitonin gene-related peptide (CGRP) and brain-derived neurotrophic factor (BDNF), and their associations with primary headache and exercise. Finally, we summarize current literature evaluating effects of exercise on primary headache in an effort to understand the benefits and disadvantages of exercise in primary headaches.

    View details for DOI 10.1007/s11916-013-0380-5

    View details for PubMedID 24234818

  • Does exercise make migraines worse and tension type headaches better? Current pain and headache reports Hindiyeh, N. A., Krusz, J. C., Cowan, R. P. 2013; 17 (12): 380-?

    Abstract

    Many non-pharmacological treatments have been implicated in the treatment of primary headache, with exercise being a common recommendation. In this review we first provide an overview of the relationship between exercise and primary headaches. We then review the physiology of pain modulation, with focus on the endogenous opioids, endocannabinoids, and neuropeptides calcitonin gene-related peptide (CGRP) and brain-derived neurotrophic factor (BDNF), and their associations with primary headache and exercise. Finally, we summarize current literature evaluating effects of exercise on primary headache in an effort to understand the benefits and disadvantages of exercise in primary headaches.

    View details for DOI 10.1007/s11916-013-0380-5

    View details for PubMedID 24234818

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