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Published in final edited form as: Neurology. 2026 Mar 12;106(7):e214760. doi: 10.1212/WNL.0000000000214760 Search in PMC Search in PubMed View in NLM Catalog Add to search International Consensus on the Evaluation and Management of Hypothalamic Hamartomas: Results from a Modified Delphi Survey Nathan T Cohen Nathan T Cohen 1. Center for Neuroscience Research, Children’s National Hospital, Washington, DC 2. Department of Neurology, George Washington University School of Medicine and Health Sciences Find articles by Nathan T Cohen 1, 2 , Xiaotong Li Xiaotong Li 1. Center for Neuroscience Research, Children’s National Hospital, Washington, DC Find articles by Xiaotong Li 1 , Madison M Berl Madison M Berl 3. Center for Neuroscience Research, Children’s National Hospital 4. Department of Psychiatry and Behavioral Sciences, The George Washington University School of Medicine and Health Sciences Find articles by Madison M Berl 3, 4 , Chima O Oluigbo Chima O Oluigbo 3. Center for Neuroscience Research, Children’s National Hospital 5. Department of Neurosurgery, George Washington University School of Medicine and Health Sciences Find articles by Chima O Oluigbo 3, 5 , Hiroshi Shirozu Hiroshi Shirozu 6. Functional Neurosurgery Center, Department of Neurosurgery, Fukuoka Sanno Hospital, Fukuoka, Japan Find articles by Hiroshi Shirozu 6 , Samuel F Berkovic Samuel F Berkovic 7. Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health,Melbourne, Victoria, Australia Find articles by Samuel F Berkovic 7 , Margaret Zacharin Margaret Zacharin 8. Department of Endocrinology and Diabetes, Murdoch Children’s Research Institute, Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia Find articles by Margaret Zacharin 8 , Wirginia Maixner Wirginia Maixner 9. Department of Neurosurgery, The Royal Children’s Hospital, Melbourne, Australia Find articles by Wirginia Maixner 9 , Andreas Schulze-Bonhage Andreas Schulze-Bonhage 10. Epilepsy Center, Medical Center, Member of the ERN EpiCARE, University of Freiburg, Freiburg,Germany Find articles by Andreas Schulze-Bonhage 10 , Kerstin Klotz Kerstin Klotz 11. Epilepsy Center, Medical Center, University of Freiburg, Freiburg, Germany Find articles by Kerstin Klotz 11 , Nicola Specchio Nicola Specchio 12. Clinical and Experimental Neurology, Epilepsy and Movement Disorders Unit, Bambino Gesù Children’s Hospital, Full Member of European Reference Network on Rare and Complex Epilepsies, EpiCARE, IRCCS, Rome, Italy Find articles by Nicola Specchio 12 , Sarah Ferrand-Sorbets Sarah Ferrand-Sorbets 13. Pediatric Neurosurgery Department, Rothschild Foundation Hospital, Member of the ERN EpiCARE Paris, France Find articles by Sarah Ferrand-Sorbets 13 , Christine Bulteau Christine Bulteau 13. Pediatric Neurosurgery Department, Rothschild Foundation Hospital, Member of the ERN EpiCARE Paris, France Find articles by Christine Bulteau 13 , Alexis A Arzimanoglou Alexis A Arzimanoglou 14. Department of Pediatric Clinical Epileptology, Sleep Disorders and Functional Neurology, Member of ERN-EpiCARE; HFME, Hospices Civils de Lyon, France; Epilepsy Unit; Barcelona’s Children Hospital San Juan de Dios, Coordinating Member of the ERN EpiCARE, Find articles by Alexis A Arzimanoglou 14 , Jean REGIS Jean REGIS 15. Institut de Neurosciences des Systèmes (INS), UMR1106, Aix-Marseille Université, Marseilles, France Find articles by Jean REGIS 15 , J Helen Cross J Helen Cross 16. UCL NIHR BRC Great Ormond Street Institute of Child Health, Supporting partner centre of ERN-EpiCARE, London; Great Ormond Street Hospital for Children, NHS Trust, London; Young Epilepsy, Lingfield, Surrey, UK Find articles by J Helen Cross 16 , Martin M Tisdall Martin M Tisdall 17. Department of Neurosurgery, Supporting partner centre of ERN-EpiCARE, Great Ormond Street Hospital, London, UK Find articles by Martin M Tisdall 17 , Hanna Richardson Hanna Richardson 18. Department of Paediatric Neurodisability, Great Ormond Street Hospital NHS Trust, London, UK Find articles by Hanna Richardson 18 , Arthur Cukiert Arthur Cukiert 19. São Paulo Epilepsy Clinic, São Paulo, Brazil Find articles by Arthur Cukiert 19 , Cristine Cukiert Cristine Cukiert 19. São Paulo Epilepsy Clinic, São Paulo, Brazil Find articles by Cristine Cukiert 19 , Julia Jacobs Julia Jacobs 20. Alberta Children’s Hospital, University of Calgary, Calgary, Alberta, Canada Find articles by Julia Jacobs 20 , Elizabeth J Donner Elizabeth J Donner 21. Division of Neurology, Department of Paediatrics, Hospital for Sick Children, University of Toronto,Toronto, Ontario, Canada Find articles by Elizabeth J Donner 21 , Phillip L Pearl Phillip L Pearl 22. Department of Neurology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA Find articles by Phillip L Pearl 22 , John F Kerrigan John F Kerrigan 23. Division of Pediatric Neurology, Barrow Neurological Institute at Phoenix Children’s Hospital,Phoenix, AZ, USA Find articles by John F Kerrigan 23 , Angus A Wilfong Angus A Wilfong 23. Division of Pediatric Neurology, Barrow Neurological Institute at Phoenix Children’s Hospital,Phoenix, AZ, USA Find articles by Angus A Wilfong 23 , Kevin CJ Yuen Kevin CJ Yuen 24. Barrow Neurological Institute, University of Arizona College of Medicine and Creighton University School of Medicine, Phoenix, AZ, USA Find articles by Kevin CJ Yuen 24 , Dennis J Dlugos Dennis J Dlugos 25. Departments of Neurology and Pediatrics, Children’s Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA Find articles by Dennis J Dlugos 25 , Daniel Curry Daniel Curry 26. Texas Children’s Hospital, Baylor College of Medicine, Houston, TX, USA Find articles by Daniel Curry 26 , Irfan Ali Irfan Ali 27. Section of Neurology and Developmental Neuroscience, Department of Pediatrics, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX, USA Find articles by Irfan Ali 27 , John Ragheb John Ragheb 28. Division of Neurological Surgery, Brain Institute Nicklaus Children’s Hospital, Miami, Florida, USA Find articles by John Ragheb 28 , Lisa Soeby Lisa Soeby 29. Hope for Hypothalamic Hamartomas, Eagle, ID, USA Find articles by Lisa Soeby 29 , Erica Webster Erica Webster 29. Hope for Hypothalamic Hamartomas, Eagle, ID, USA Find articles by Erica Webster 29 , William D Gaillard William D Gaillard 3. Center for Neuroscience Research, Children’s National Hospital 30. Department of Neurology, George Washington University School of Medicine and Health Sciences,Washington, DC Find articles by William D Gaillard 3, 30 Author information Article notes Copyright and License information 1. Center for Neuroscience Research, Children’s National Hospital, Washington, DC 2. Department of Neurology, George Washington University School of Medicine and Health Sciences 3. Center for Neuroscience Research, Children’s National Hospital 4. Department of Psychiatry and Behavioral Sciences, The George Washington University School of Medicine and Health Sciences 5. Department of Neurosurgery, George Washington University School of Medicine and Health Sciences 6. Functional Neurosurgery Center, Department of Neurosurgery, Fukuoka Sanno Hospital, Fukuoka, Japan 7. Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health,Melbourne, Victoria, Australia 8. Department of Endocrinology and Diabetes, Murdoch Children’s Research Institute, Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia 9. Department of Neurosurgery, The Royal Children’s Hospital, Melbourne, Australia 10. Epilepsy Center, Medical Center, Member of the ERN EpiCARE, University of Freiburg, Freiburg,Germany 11. Epilepsy Center, Medical Center, University of Freiburg, Freiburg, Germany 12. Clinical and Experimental Neurology, Epilepsy and Movement Disorders Unit, Bambino Gesù Children’s Hospital, Full Member of European Reference Network on Rare and Complex Epilepsies, EpiCARE, IRCCS, Rome, Italy 13. Pediatric Neurosurgery Department, Rothschild Foundation Hospital, Member of the ERN EpiCARE Paris, France 14. Department of Pediatric Clinical Epileptology, Sleep Disorders and Functional Neurology, Member of ERN-EpiCARE; HFME, Hospices Civils de Lyon, France; Epilepsy Unit; Barcelona’s Children Hospital San Juan de Dios, Coordinating Member of the ERN EpiCARE, 15. Institut de Neurosciences des Systèmes (INS), UMR1106, Aix-Marseille Université, Marseilles, France 16. UCL NIHR BRC Great Ormond Street Institute of Child Health, Supporting partner centre of ERN-EpiCARE, London; Great Ormond Street Hospital for Children, NHS Trust, London; Young Epilepsy, Lingfield, Surrey, UK 17. Department of Neurosurgery, Supporting partner centre of ERN-EpiCARE, Great Ormond Street Hospital, London, UK 18. Department of Paediatric Neurodisability, Great Ormond Street Hospital NHS Trust, London, UK 19. São Paulo Epilepsy Clinic, São Paulo, Brazil 20. Alberta Children’s Hospital, University of Calgary, Calgary, Alberta, Canada 21. Division of Neurology, Department of Paediatrics, Hospital for Sick Children, University of Toronto,Toronto, Ontario, Canada 22. Department of Neurology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA 23. Division of Pediatric Neurology, Barrow Neurological Institute at Phoenix Children’s Hospital,Phoenix, AZ, USA 24. Barrow Neurological Institute, University of Arizona College of Medicine and Creighton University School of Medicine, Phoenix, AZ, USA 25. Departments of Neurology and Pediatrics, Children’s Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA 26. Texas Children’s Hospital, Baylor College of Medicine, Houston, TX, USA 27. Section of Neurology and Developmental Neuroscience, Department of Pediatrics, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX, USA 28. Division of Neurological Surgery, Brain Institute Nicklaus Children’s Hospital, Miami, Florida, USA 29. Hope for Hypothalamic Hamartomas, Eagle, ID, USA 30. Department of Neurology, George Washington University School of Medicine and Health Sciences,Washington, DC Group Authorship: No. There is no study group involved in our research Contributions: Nathan Cohen: Drafting/revision of the manuscript for content, including medical writing for content; Major role in the acquisition of data; Study concept or design; Analysis or interpretation of data; Xiaotong Li: Major role in the acquisition of data; Analysis or interpretation of data; Madison Berl: Drafting/revision of the manuscript for content, including medical writing for content; Major role in the acquisition of data; Analysis or interpretation of data; Chima Oluigbo: Major role in the acquisition of data; Analysis or interpretation of data; Hiroshi Shirozu: Drafting/revision of the manuscript for content, including medical writing for content; Major role in the acquisition of data; Samuel Berkovic: Drafting/revision of the manuscript for content, including medical writing for content; Major role in the acquisition of data; Margaret Zacharin: Drafting/revision of the manuscript for content, including medical writing for content; Major role in the acquisition of data; Wirginia Maixner: Drafting/revision of the manuscript for content, including medical writing for content; Major role in the acquisition of data; Andreas Schulze-Bonhage: Drafting/revision of the manuscript for content, including medical writing for content; Major role in the acquisition of data; Kerstin Klotz: Drafting/revision of the manuscript for content, including medical writing for content; Major role in the acquisition of data; Nicola Specchio: Drafting/revision of the manuscript for content, including medical writing for content; Major role in the acquisition of data; Sarah Ferrand-Sorbets: Drafting/revision of the manuscript for content, including medical writing for content; Major role in the acquisition of data; Christine Bulteau: Drafting/revision of the manuscript for content, including medical writing for content; Major role in the acquisition of data; Alexis Arzimanoglou: Drafting/revision of the manuscript for content, including medical writing for content; Major role in the acquisition of data; Jean REGIS: Drafting/revision of the manuscript for content, including medical writing for content; Major role in the acquisition of data; J. Cross: Drafting/revision of the manuscript for content, including medical writing for content; Major role in the acquisition of data; Martin Tisdall: Drafting/revision of the manuscript for content, including medical writing for content; Major role in the acquisition of data; Hanna Richardson: Drafting/revision of the manuscript for content, including medical writing for content; Major role in the acquisition of data; Arthur Cukiert: Drafting/revision of the manuscript for content, including medical writing for content; Major role in the acquisition of data; Cristine Cukiert: Drafting/revision of the manuscript for content, including medical writing for content; Major role in the acquisition of data; Julia Jacobs: Drafting/revision of the manuscript for content, including medical writing for content; Major role in the acquisition of data; Elizabeth Donner: Drafting/revision of the manuscript for content, including medical writing for content; Major role in the acquisition of data; Phillip Pearl: Drafting/revision of the manuscript for content, including medical writing for content; Major role in the acquisition of data; John Kerrigan: Drafting/revision of the manuscript for content, including medical writing for content; Major role in the acquisition of data; Angus Wilfong: Drafting/revision of the manuscript for content, including medical writing for content; Major role in the acquisition of data; Kevin Yuen: Drafting/revision of the manuscript for content, including medical writing for content; Major role in the acquisition of data; Dennis Dlugos: Drafting/revision of the manuscript for content, including medical writing for content; Major role in the acquisition of data; Daniel Curry: Drafting/revision of the manuscript for content, including medical writing for content; Major role in the acquisition of data; Irfan Ali: Drafting/revision of the manuscript for content, including medical writing for content; Major role in the acquisition of data; John Ragheb: Drafting/revision of the manuscript for content, including medical writing for content; Major role in the acquisition of data; Lisa Soeby: Drafting/revision of the manuscript for content, including medical writing for content; Major role in the acquisition of data; Erica Webster: Drafting/revision of the manuscript for content, including medical writing for content; Major role in the acquisition of data; William D. Gaillard: Drafting/revision of the manuscript for content, including medical writing for content; Major role in the acquisition of data; Study concept or design; Analysis or interpretation of data; ✉ Corresponding Author: Nathan Cohen Issue date 2026 Apr 14. PMC Copyright notice PMCID: PMC13031823 NIHMSID: NIHMS2158984 PMID: 41818657 The publisher's version of this article is available at Neurology Abstract Background and Objectives: Hypothalamic hamartomas (HH) are rare brain lesions associated with epilepsy and numerous comorbidities. Worldwide treatment is varied. There is a paucity of high-quality evidence to guide treatment. This study aimed to establish expert consensus on the evaluation and management of HH. Methods: A modified Delphi survey was designed by the Medical Advisory Board of Hope for Hypothalamic Hamartomas and was conducted among 17 ILAE Level II epilepsy surgery centers. The survey included 257 questions in Round 1 and 81 refined questions in Round 2, covering domains of diagnosis, imaging, medical and surgical treatment, neuropsychological and psychiatric evaluation, and care. Consensus was defined as ≥75% agreement using a 9-point Likert scale. Results: Consensus was achieved on 82% of the questions. Key findings include: Diagnosis : Gelastic and dacrystic seizures are strongly associated with HH; 3T epilepsy protocol MRI is essential. Evaluation : Preoperative neuropsychological and endocrinological assessments are important. Evaluation with further imaging (PET, SPECT, MEG) and intracranial EEG is not useful. Treatment: No consensus was achieved on 1 st -, 2 nd - or 3 rd -line antiseizure medications (ASM). Surgical evaluation should begin at the start of the 1 st ASM, with surgery recommended after failure of two ASMs. LITT is preferred for Delalande II and III HH. Postoperative Care: MRI follow-up at 6–12 months recommended. Pre- and postoperative cognitive, behavioral, psychosocial, and endocrinological evaluations are emphasized. Domains: IQ, language, attention, executive function, academic achievement, adaptive function, and behavior (tantrums, rage, anxiety, depression) are important. Discussion: This Delphi process highlights an international consensus on aspects of HH management. Gelastic/dacrystic seizures are important at diagnosis. A 3T epilepsy protocol MRI is essential. Early epilepsy surgery evaluation is advised. Surgery should be pursued either by disconnective, ablative, or resective techniques. HH location, size, and surgical experience are essential for good outcomes. Postoperative MRI should be obtained 6–12 months and/or if ongoing seizures. Neuropsychological testing should be obtained at baseline, and 6–12 months postsurgically. Findings support a multidisciplinary, protocol-driven approach to optimize outcomes in patients with HH. Areas lacking consensus, such as specific endocrine testing and timing of certain interventions, warrant further research and standardization. Search Terms: drug-resistant epilepsy, epilepsy surgery, magnetic resonance imaging, malformation of cortical development, gelastic seizures, dacrystic seizures, comorbidity Introduction: Hypothalamic hamartomas (HH) are rare, congenital brain malformations that are usually associated with drug-resistant epilepsy (DRE) and a spectrum of neurodevelopmental, neuropsychological and endocrine comorbidities. 1 HH syndrome affects about 1 in 200,000 individuals 2 , but management practices vary widely 1 , 3 The characteristic gelastic seizure, or spells of mirthless laughter, often occur without surface EEG correlate which can complicate the work-up. These, and other typical dacrystic (or paroxysmal events of crying) seizures can be difficult for families or providers to recognize, adding to delayed care. The typical initial presentation involves a combination of DRE and/or endocrine dysfunction such as precocious puberty and obesity. 4 Despite HH being linked to precocious puberty in 1934, to seizures in 1958 5 , and the epilepsy syndrome being well-characterized in 1988 6 , there is still a paucity of high-quality data and no consensus guidelines many decades later to guide diagnosis and treatment. Given there is under-recognition of the disease, the deep location of the epileptogenic lesion in the hypothalamus, the complicated presentation and management of the HH syndrome, the broad and distinct comorbidities (some psychiatric, several endocrine) which are underappreciated or known, and the variety of surgical management strategies, broader guidance is needed beyond existing management strategies for typical cortical drug-resistant epilepsies. The purpose of this study was to establish consensus on evaluation and management strategies for HH using a modified Delphi process from experts across international epilepsy centers. Methods: Standard Protocol Approvals, Registrations, and Patient Consents This study was approved as exempt by the Institutional Review Board of Children’s National Hospital (CNH) in Washington, DC. Data Availability Survey data are available upon reasonable request from a qualified investigator. Survey Design and Representativeness A modified Delphi survey regarding the diagnosis and management of HH was designed to evaluate core areas as proposed at the 2019 International Symposium on Hypothalamic Hamartomas in Washington, DC. The first round of the survey was discussed at the 2022 International Symposium on HH in Calgary. The second round of the survey was sent after the Calgary meeting, with final results presented at the 2025 International Symposium on HH in Barcelona. These Symposia are run by Hope for Hypothalamic Hamartomas, the largest international patient- and family-driven non-profit organization dedicated to research and treatment for HH. The questions for the survey were designed by the Medical Advisory Board of Hope for HH which includes world experts in HH medical, surgical and comorbidity management comprised of pediatric epilepsy surgeons, pediatric epileptologists, neuropsychologists, endocrinologists, and researchers with extensive experience in basic, clinical and translational research on the disease. To ensure inclusiveness, survey question topics were generated by focus groups on core areas at the International Symposium which included clinicians, researchers, patients and caregivers from around the world. The limited existing evidence, where available, was reviewed or discussed by the session leaders. These core areas included Clinical, Surgical, Endocrine, Imaging, and Neuropsychology/Psychiatry. The initial phase included drafting and review of questions. Survey questions were written to address issues related to Primary Diagnosis, Treatment and Care Decisions (Diagnostic Testing and Medical Treatment), Surgical Treatments (Selection/choice of surgical approaches, and evaluation of complications), Neuroimaging (Pre-diagnosis, as related to the surgical evaluation, and postoperative imaging recommendations), and recommendations for evaluation and management of Neuropsychological and Psychiatric comorbidities. A modified Delphi survey was conducted among 24 invited International League Against Epilepsy (ILAE) Level II epilepsy centers based on participation in an ILAE Pediatric Epilepsy Surgery Task Force surveys that established technical aspects and worldwide criteria for pediatric epilepsy surgery centers. 7 , 8 These include ILAE Pediatric Epilepsy Surgery Task Force members and ILAE-certified centers from low-middle to high-income countries. Centers also had to be recognized by the Hope for HH Medical Advisory Board as having experience in treating HH. The survey was conducted in two rounds. The first round consisted of 257 questions taking about 1 hour to complete. Each center had a designated survey respondent. Domain-specific answers were provided by subspecialist experts at each center through the designee. For Round 1, a 9-point Likert scale was clustered for analysis as: 1–3 indicating “important/necessary,” 4–6 indicating “no strong view,” and 7–9 indicating “not important/unnecessary.” Answers achieving “important/necessary” or “not important/unnecessary” categories with ≥75% of responding centers achieved consensus. Questions with 55–74% agreement were revised and re-evaluated in Round 2. Here, questions were clarified or reworded if poorly phrased. Questions with near consensus (65–74% agreement from Round 1) were presented with the near-consensus result. Round 2 consisted of 81 questions. Questions in Round 2 were voted on using up or down scoring (e.g., agree or disagree with the majority). Comments were collected (if needed) for those in disagreement. Consensus was defined as ≥75% agreement of responding centers. Questions for Round 1 and Round 2 are listed in Supplemental Material . Results: Table 1 summarizes survey respondent and surgical center characteristics. Table 1: Center and Respondent Characteristics Specialist Type n (%) or mean (range) Neurologists 4 (12.5) Pediatric Neurologists 8 (25) Neurosurgeons 12 (37.5) Neuropsychologists 4 (12.5) Endocrinologist 1 (3.1) Neuroradiologists 3 (9.4) Other 1 (3.1) Average # Cases/year 10.5 (2–25) Average # Total Cases 67 (10–250) Centers NHO Nishiniigata Chuo Hospital, Niigata, Japan The Royal Children’s Hospital, Melbourne, Australia University Medical Center, Univ. of Freiburg, Germany Bambino Gesù Children’s Hospital, Rome, Italy Foundation Hospital, Paris, France Hospices Civils de Lyon, Lyon, France Aix Marseille University, Marseille, France Great Ormond Street Hospital, UK São Paulo Epilepsy Clinic, São Paulo, Brazil Alberta Children’s Hospital, Calgary, Canada Hospital for Sick Children Toronto, Canada Boston Children’s Hospital, MA, USA Phoenix Children’s Hospital, AZ, USA Children’s National Hospital, Washington, DC, USA Children’s Hospital of Philadelphia, PA, USA Texas Children’s Hospital, Houston, TX, USA Nicklaus Children’s Hospital, Miami, FL, USA Open in a new tab This table shows the expertise of survey respondents. Note: Other means the training section was left blank. The mean (and range) number of annual as well as all-time surgical hypothalamic hamartoma cases performed by centers. For Round 1, identified respondents included 32 specialists from 17 centers (70% of centers) in five continents: North America (n=8); Europe (n=6); Asia (n=1); Australia (n=1); South America (n=1). Of the 257 questions in Round 1, consensus could not be reached for 45 (18%) questions. For Round 2, of 81 questions administered, there were 3 clarifying questions proposed, and consensus could not be achieved in 2 (2%) questions. Responses to the survey were as follows (organized by core section, with clustered Likert scale responses for each answer provided). Primary Diagnosis The diagnosis of hypothalamic hamartoma should be considered when presenting seizures are gelastic (likely), dacrystic (likely), intractable (no consensus), focal (unlikely); when endocrine symptoms are present (likely). Treatment and Care: Evaluation Diagnostic Testing Table 2 summarizes the key recommendations regarding diagnostic testing for HH. The only unanimous response was that a 3T MRI brain with epilepsy protocol including high-resolution 3D T1-weighted sequence with ≤1 mm 3 voxels, 3D FLAIR, and T2 sequences in two planes is important (essential per ILAE guidelines). 9 , 10 Additional MRI sequences were not viewed as important. Table 2: Consensus Recommendations on Diagnostic Testing. EEG (electroencephalography); HARNESS (Harmonized Neuroimaging of Epilepsy Structural Sequences); FLAIR (Fluid Attenuated Inversion Recovery); FDG-PET (Fluorodeoxyglucose-Positron Emitted Tomography) Diagnostic Testing Caveat/Explanation Important (I) Video EEG Can be falsely assuring or localizing 3T Epilepsy Protocol Brain MRI * 1.5T MRI (I) but 3T is preferred Endocrine testing Both endocrine + neuropsychological Neuropsychological Testing testing (I) at diagnosis Near Consensus Cell phone video Near consensus, but 73% (I) Not Important (NI) Routine EEG 3D Source Localization Magnetoencephalography (MEG) Intracranial EEG Neuroimaging Important (I) 3T HARNESS protocol: high-res 3D T1-weighted (≤1 mm3 voxels) 3D FLAIR T2-weighted sequences in 2 planes No Consensus Diffusion weighted imaging Not Important (NI) Computed tomography (CT) Ultrasound Functional MRI (fMRI) FDG-PET MR-spectroscopy Ictal single photon emission computed tomography (SPECT) Open in a new tab This table summarizes the Delphi consensus results on diagnostic testing. The left column summarizes the panel vote. The middle column summarizes the tests. The right column describes caveat statements that achieved consensus from the panel or has explanatory information. Endocrine and neuropsychological testing were felt to be important at the diagnosis of HH, as well as part of the presurgical evaluation which for practical purposes might be initiated at diagnosis (see below). Gelastic Epilepsy When focusing on gelastic epilepsy, participants reached consensus that gelastic seizures are likely present longer than reported when the parent is questioned about their presence in history-taking. There was agreement as well that parents are often unaware of the presence of gelastic seizures, which can be diagnosed on video EEG. Gelastic seizures are not pathognomic of HH and may arise from temporal or frontal lobe generators which may sometimes be clarified by video EEG. Antiseizure medication choice should be based on the specific seizure type being treated. Respondents agreed that patients are diagnosed when they exhibit gelastic seizures. Most patients have a longer history of gelastic seizures prior to their diagnosis when questioned directly. MRIs should be re-reviewed, and new, repeat 3T epilepsy protocol brain MRI should be considered if not performed in patients with clear gelastic seizures and reportedly negative MRI. In some cases, parents and patients are not aware of gelastic seizures but that they can become evident from video EEG monitoring. As in Table 2 , respondents were also asked about the importance of cell phone video which did not achieve consensus. Treatment and Care; Medical Treatment and Beginning Surgical Evaluation There was no consensus about first-choice antiseizure medication but oxcarbazepine/carbamazepine and levetiracetam/brivaracetam were voted as top choices. There was no consensus on second-choice or third-choice antiseizure medications. Table 3 shows the results of recommendations for first, second and third-choice antiseizure medications in HH-related epilepsy. There was agreement that epilepsy surgery should be considered after the failure of the second appropriately-selected, adequately-dosed antiseizure medication. However, there was agreement that the presurgical evaluation should begin coinciding with the start of the first antiseizure medication. There was no consensus about surgical consideration after the failure of the first antiseizure medication. There was consensus not to offer surgery without trial of an antiseizure medication, and waiting beyond failure of three or more antiseizure medications is too late. Table 3: Voting for First, Second and Third-Choice Antiseizure Medications (ASM) ASM First Second Third Oxcarbazepine/Carbamazepine 7 4 Levetiracetam/ Brivaracetam 5 4 3 Valproic Acid 2 1 2 Phenytoin 1 1 1 Clobazam 1 2 1 Lamotrigine 4 3 Lacosamide 1 1 Topiramate 1 2 Vigabatrin 1 Zonisamide 4 Open in a new tab Surgical Treatment There was agreement that the surgical strategy should disconnect or completely remove the hypothalamic hamartoma, or to disconnect and partially remove the HH leaving some tissue behind. There was also no consensus about pursuit of repeat surgery to achieve seizure freedom. On clarification, there was agreement that for patients with seizures, an intervention with the goal to remove or disconnect the HH is most promising; and there was agreement that a disconnection may lead to seizure-free outcome even if the majority of the HH tissue remains untouched. Surgical Treatment Availability Eighty-eight percent (n=15/17) of centers offer endoscopic or transcallosal resection; 82% (14/17) offer skull base surgery. 71% of centers (12/17) offer laser interstitial thermal therapy (LITT), gamma knife surgery, or radiofrequency thermocoagulation. A minority of centers, 20% (3/15), offer high frequency focused ultrasound. Endoscopic, transcallosal, skull base surgeries and HiFUS do not require referrals, whereas LITT, gamma knife surgery and RFTC do. Surgical Treatment: Considerations There was consensus on the importance of surgical experience with the specific procedure being offered. The size and location of the lesion are important for selection of surgical strategy. The severity of the epilepsy was rated as important. The center should have expertise in management of HH (important). There was no consensus about the age at which surgery should be offered. There was consensus agreement that insurance status is not important when considering surgery for a patient with HH. Although there are several classifications of HH, the Delalande classification is most widely adopted. Briefly, the Delalande schema is as follows: Class 1 (horizontal insertion below floor of third ventricle); Class 2 (vertical insertion along wall of third ventricle); Class 3 (horizontal and vertical attachment above and below floor of third ventricle); and Class 4 (giant HH greater or equal to 8 cm 3 ). 11 Table 4 summarizes the survey results for minimum age and specific treatment recommendations by Delalande class. Table 4: Consensus on Age Consideration and Treatment Options by Delalande Class. LITT (Laser interstitial thermal therapy); GKS (Gamma knife surgery); RFTC (radio frequency thermocoagulation); Endo (endoscopic resection); Trans CC (transcallosal); NC (no consensus). LITT GKS RFTC Endo Trans CC Skull Base Med Rx /No Surg Minimum Age NC NC NC No limit* No limit* No limit* Delalande 1 NC NC NC NC NC NC Inappropriate Delalande 2 Appropriate NC NC NC NC Inappropriate Inappropriate Delalande 3 Appropriate NC NC NC NC NC Inappropriate Delalande 4 NC NC NC NC NC NC Inappropriate Open in a new tab After Diagnosis There was consensus agreement that there should be referral for endocrine evaluation for all HH patients. Ideally, the endocrine follow-up can be timed to coincide with neurology follow-up (care coordination). Respondents disagreed with the statement that follow-up is not needed. MRI MRI is essential pre-diagnosis (consensus). Once confirmed on high-resolution epilepsy protocol MRI, there was agreement that additional preoperative MRI sequences are unnecessary. 70% of respondents (12/17) obtained an intraoperative MRI (this question did not specify for which type of procedure). There was no consensus for obtaining a postoperative MRI on the same day, within 24 hours of surgery, or within 48 hours of surgery. MRI within 1–2 weeks postoperatively was rated as too late. There was consensus that a single postoperative MRI should be obtained within 6–12 months of surgery, but no consensus about the exact timing. Once obtained, further postoperative MRI is only recommended if there are ongoing seizures (consensus). Behavioral/Cognitive Focus Neuropsychological evaluation for cognition was rated important. Behavioral and psychosocial evaluations were also ranked important. Psychiatric evaluation was recommended for treatment need and medication prescription. There was no consensus on the need for occupational therapy or for physical therapy. Evaluation The behavioral/cognitive evaluation was ranked as important for the following reasons: 1) to establish baseline functioning; 2) to determine the presence of comorbidity such as intellectual and developmental disability, autism spectrum disorder, or attention deficit hyperactivity disorder; 3) to determine necessary interventions (behavioral, medication); 4) to determine necessity of support services for school; and 5) to determine necessity of support services for the family. Within the cognitive evaluation, respondents felt the following areas were important for testing: 1) attention/executive function; 2) memory; 3) language; 4) intelligence quotient; 5) academic achievement. There was no consensus on the importance of evaluation of visuospatial and motor skills. For the behavioral evaluation, respondents ranked the following areas as important for assessment: 1) anxiety; 2) mood/depression; 3) behavior; 4) rage/aggression. Respondents also rated assessment of social functioning as important in the following areas: 1) social skills/peer relationships; 2) family functioning/parental stress; 3) atypical behaviors (including mirthless laughter and atypical eating). There was no consensus if the presence or absence of seizures alters these recommendations. Preoperative Evaluation Respondents rated numerous domains of cognition and behavior as important for preoperative evaluation (which may be the same as initial evaluation). These included: 1) intelligence quotient; 2) language; 3) visuospatial skill; 4) attention; 5) executive function; 6) memory; 7) motor skills; 8) academic achievement; 9) adaptive function; 10) social cognition. Additionally, preoperative evaluation for anxiety, depression, behavioral tantrums, rage and aggression, as well as atypical behaviors were rated as important. Postoperative Evaluation The timing and necessity of postoperative neuropsychological and psychosocial evaluations were rated. Respondents felt these evaluations should occur at minimum once (important), and preferably with ongoing surveillance (multiple evaluations) (important). There was agreement that postoperative evaluation should occur between 6–12 months without consensus being achieved for 6 or 12 months; 73% of respondents (plurality) recommended 12 months postoperatively for evaluation. 1 month postoperatively was rated too early, and 18 months or longer was too long. There was no consensus about whether specific age considerations should alter these recommendations. Discussion Hypothalamic hamartomas are rare, developmental brain malformations that cause a syndrome of drug-resistant epileptic encephalopathy. There are numerous comorbidities associated with the disease and its treatment. Despite knowledge of the existence of HH and its association with precocious puberty (> 90 years), with seizures (>60 years), and with the epilepsy syndrome (> 35 years), there is still wide variability in the diagnosis and treatment of the disorder. This international, multidisciplinary, modified Delphi survey of practitioners from 17 ILAE level II epilepsy centers in eight countries across five continents establishes consensus recommendations for the diagnosis, management and treatment of the HH syndrome and its wide-ranging comorbidities. Overall, this international, modified Delphi survey achieved consensus on 82% of questions, helping to clarify areas of importance the diagnosis and medical/surgical management of the HH syndrome and its comorbidities. I. Diagnosis: a). Neuroimaging: There are no current guidelines for the diagnosis and treatment of hypothalamic hamartomas. MRI has been recommended as the gold standard for imaging (since the 1980s) due to its superior resolution and ability to clearly delineate anatomical associations. 1 , 3 , 6 The lesions are easily distinguished from normal hypothalamic grey matter, and best appreciated on T2-weighted sequences. 12 The 2019 ILAE Consensus on Structural Neuroimaging for Patients with Epilepsy recommends the Harmonized Neuroimaging of Epilepsy Structural Sequences high-resolution 3 Tesla (or 1.5 Tesla when 3T unavailable) MRI for all patients with new onset seizure. 9 The HARNESS protocol includes high-resolution 3D T1-weighted sequence, 3D FLAIR, and 2D coronal T2-weighted sequence acquired perpendicular to the long axis of the hippocampus. Pediatric imaging guidelines include T2 imaging in two directions. 10 Thus, T2 sequences should be obtained in any pediatric patient with suspicion for HH. High-resolution epilepsy protocol MRI will detect HH, but the neuroradiologist/epilepsy team need to be skilled and specifically looking for HH. New clinical data that raise concern for HH syndrome should prompt re-review of prior neuroimaging and neurophysiological work-up to try to identify a lesion. Consensus: Gelastic and dacrystic seizures (characterized as mimetic automatisms in the 2025 ILAE classification of seizures 13 ) are considered important when considering the primary diagnosis. High-resolution epilepsy protocol 3 Tesla MRI is essential to the initial evaluation. Head CT, ultrasound, functional MRI, FDG-PET, MR Spectroscopy, and ictal SPECT were rated as not important and are unnecessary. b). EEG: The role of EEG holds important limitations and requires skill in interpretation. Although gelastic seizures are common at onset (up to 77% of patients), 75% of gelastic seizures have no associated scalp EEG correlate; seizures with ictal EEG correlate have high rates of false localization suggesting scalp EEG may be of limited use in seizure localization. 14 , 15 EEG findings, in particular, should not influence the surgical decision given their unreliability. The video clinical characterization of events, however, may be diagnostic with the EEG best not being over-interpreted. The HH tissue is known to be the generator of gelastic seizures as confirmed by stereoEEG. 16 There is no role for stereoEEG in the diagnosis and management of HH syndrome. Consensus: Routine EEG was rated as not important. Video EEG was rated as important (with disclaimer of potential for false negativity, or false localization/lateralization). Intracranial EEG was rated as not useful in the initial diagnosis of HH. Additional neurophysiological studies such as 3D source localization and MEG were also ranked not important. c). Psychiatric/Behavioral/Cognitive: HH syndrome is associated with a wide array of neuropsychological, cognitive, behavioral and psychiatric comorbidities. Fifty-five percent of HH patients are affected by a psychiatric comorbidity. 17 There are high rates of oppositional defiant disorder, attention deficit hyperactivity disorder, conduct disorder, autism spectrum disorder, and other affective disorders. 18 – 21 These comorbidities have similar rates of presentation as seen in other focal lesional epilepsies. The exception is the rage attacks which are commonly seen in HH. Behavioral comorbidities may predate seizures. 1 Aggression is more likely with the following: male gender; younger age of seizure onset; presence of intellectual disability; or multiple seizure types. 22 Presurgical developmental delay or intellectual disability is reported in ~50% of patients with some centers now using these data to inform surgical timing. 17 , 23 HH patients often have visual and verbal memory deficits, executive dysfunction, and other wide-ranging cognitive dysfunction. 24 Deficits in long-term retrieval and processing speed are frequent. 25 Similar to epilepsy in general, worse cognitive functioning is associated with early age of seizure onset, more frequent seizures, larger lesion size, and taking more ASMs. 26 – 28 Studies from more recent surgical cohorts with minimally invasive techniques show cessation of cognitive declines and sometimes improvement postoperatively. 27 – 29 Consensus: There were consensus recommendations on preoperative evaluation. Neuropsychological evaluation was rated as important especially for assessing cognitive, behavioral, and social impacts on the patient. Behavioral and cognitive evaluations should be established at baseline including comorbidity assessments and should be re-checked 6 to 12 months postoperatively. The emphasis of these evaluations should include focusing on tantrums, rage, memory, intelligence quotient, language, attention, executive function, academic achievement, as well as adaptive skills. Given the high rate of psychiatric comorbidities experienced by patients with HH, it is recommended to obtain psychiatric evaluation at baseline to evaluate for medication management and therapeutic needs. d). Endocrine Evaluation: There are several endocrinological problems associated with HH syndrome. Between forty and sixty-seven percent of patients present with precocious puberty 30 , 31 , which may require ongoing treatment even after surgical treatment. Other endocrine disorders include advanced skeletal maturation (from the CPP) but with reduction in growth velocity; secondary (thyroid-stimulating hormone) or tertiary (thyrotropin-releasing hormone) hypothyroidism; and hypothalamic obesity syndrome. 4 Postoperatively, hypernatremia (from arginine vasopressin deficiency (diabetes insipidus)) can occur; growth hormone deficiency; adrenal insufficiency; hypogonadism; hypothyroidism; and weight gain are also reported. 32 Consensus: Endocrine referral should be pursued for all HH patients at diagnosis. There was no consensus on which endocrine tests to be performed at diagnosis, or across treatment. It was recommended to have multidisciplinary endocrine follow-up (especially post-operatively) to be timed with neurological follow-up when possible. II). Treatment a). Medical Management: Most patients with HH syndrome develop drug-resistant epilepsy that usually starts with gelastic seizures. 1 , 33 The purpose of antiseizure medication treatment is to try to control seizures and prevent progression of epilepsy, and especially to limit generalized tonic-clonic (convulsive) seizures due to their risk of morbidity and mortality. Treatment strategies should be individualized to the patient. 4 Consensus: There was no consensus achieved on optimal first-choice antiseizure medication. However, sodium channel drugs such as oxcarbazepine/carbamazepine, and SV2A-receptor modulators such as levetiracetam/brivaracetam received the most votes as first options. There are no data for superior efficacy of any of the antiseizure medications. Of note, all antiseizure medications are used with the goal of seizure control and all have different side effect profiles. These known risks must be weighed against efficacy when used. Consensus failed to be achieved for second or third-line antiseizure medications. b). Surgical Management There are numerous surgical strategies that can be used to treat HH syndrome. These include open versus minimally-invasive techniques, as well as various ablative procedures. High-level recommendations from Jacobs & Hildebrand were synthesized from recent meta-analyses of over 500 patients 34 – 36 : 1) minimally invasive procedures are more effective and less complicated than open (micro)surgical techniques; 2) radiosurgical techniques have lower complication rates but delays in seizure cessation; 3) overall seizure-free rates are higher than ongoing medical therapy, and early surgical intervention should be offered. 3 A systematic review/meta-analysis of 64 studies and 517 patients evaluated surgical outcomes and risks across all modern HH surgical options. 36 The major findings were that radiofrequency thermocoagulation and MRI-guided LITT achieved the highest rates of seizure-free outcome (78.5 and 74.5%). Surgical failure is more likely if there are multiple seizure types or if the patient had prior surgery. This meta-analysis also directly compared postoperative complications across different techniques at both study-level and individual patient data-level. From the study-level analysis, Stereotactic radiosurgery was the safest option with pooled major complication rate of 0.0% (95%CI: 0.0–1.4%). Open microsurgery had the largest rate of major complications with pooled proportion of 29.1% (9.5–54.2%). There were no differences in major complications between RFTC and MRgLITT. From the individual participant data meta-analysis, overall postsurgical complications were reported most in open microsurgery (54.6%) and least in SRS (1.8%). Major complications were also most common in open microsurgery (33%), and least in SRS (1.8%). Neurologic complications (motor/visual deficits) were reported in 2.8% overall most commonly in MRgLITT, 6.2% and open microsurgery, 5.2%; and 0.0% in endoscopic, SRS, or RFTC. Surgical complications (hemorrhage or infection) were reported in 0.3% overall, most frequently in open microsurgery, 1.0%; and 0.0% in endoscopic, SRS, MRgLITT or RFTC. Hypothalamic complications (hyperphagia, poikilothermia, polydipsia) were reported overall in 7.0% overall, most frequently in open microsurgery, 16.5% and endoscopic, 6.7%; SRS, 1.8%; and 0.0% in MRgLITT and RFTC. Endocrine complications (hormone deficiencies, diabetes insipidus) were reported in 4.9% overall, most commonly in open microsurgery 13.4%; RFTC, 3.2%; endoscopic, 2.2%; and 0.0% in SRS or MRgLITT. Behavioral complications (behavioral disturbances) were reported in 0.9% overall, most in open microsurgery, 2.1%; and 0.0% in endoscopic, SRS, MRgLITT or RFTC. Cognitive complications (any deficit in cognitive domain especially memory) were reported in 3.4% overall, most commonly in MRgLITT, 9.2%; open microsurgery 4.1%; endoscopic, 2.2%; and 0.0% in SRS or RFTC. Of note, complication rates (including many 0% rates) are as reported from this study design, which may not represent full real-world experience, and may suffer from underreporting. Future prospective and randomized controlled trial data would more clearly delineate complication rates. Consensus: The panel felt it was important to begin the consideration of epilepsy surgical evaluation at the time of diagnosis after starting the first antiseizure medication and certainly when the second antiseizure medication has failed the child. This is in line with ILAE Surgical Therapies Commission Recommendations meant to prevent surgical delays, especially in highly epileptogenic lesions in non-eloquent regions. 37 There were questions to operate at diagnosis or after the failure of one antiseizure medication; some respondents felt this was enough of a threshold to perform surgery however this did not achieve consensus. Emerging data from other highly epileptogenic lesions such as focal cortical dysplasia suggest consideration of surgery after the failure of just one antiseizure medication given the high rate of conversion to drug-resistant epilepsy and noted good surgical outcomes in this pathology. 38 Early epilepsy surgical evaluation (before failure of 2 ASMs) is associated with better surgical outcomes 39 and early epilepsy surgical intervention may lead to fewer comorbidities. 40 Surgery should be pursued with the goal of disconnection or removal of the epileptogenic HH tissue. Overall, epilepsy surgery for HH is safe with limited morbidity and no significant risk of mortality. After surgery, a repeat 3 Tesla epilepsy protocol MRI should be obtained between 6 and 12 months postoperatively, with further imaging as needed if ongoing seizures after this time. The recently reported data on surgical complications noted above replaces clinical views on surgical approach risks that were qualitative, and the term “common” was not defined. There are several potential limitations to this modified Delphi survey. There is potential selection bias due to the nature of the study design being based on prior participation in a pediatric neurosurgical survey among ILAE Level II epilepsy centers. The survey responses are skewed to North American and European centers and some treatment options available in certain regions may not be yet available broadly. There was limited representation of Asian and South American centers (although several invited to participate), and no African centers. For surgical recommendations, some centers may have been biased toward their center’s expertise in certain (few) techniques. These recommendations represent the best available (although potentially biased) expert opinions of ILAE Level 2 epilepsy surgical centers whose broad clinical exposure with HH management affords expertise in surgical recommendations, even for procedures not performed at those institutions. Future prospective trials could help to clarify surgical efficacy and risks more rigorously, but are difficult to implement given the rarity of the disorder. As much as possible, this survey was designed to provide optimal care through diagnostic and treatment recommendations that could be implemented in most care settings. Further, although this modified Delphi survey had broad participation with at least 32 multidisciplinary specialists from 17 international epilepsy centers, there is potential nonresponse bias. A limitation is that not all centers acknowledged subspecialist training backgrounds. Thus, these survey results likely represent a broader perspective than the 32 identified participants. Some consensus statements provide general recommendations without the clarity of specification such as which specific endocrinological testing should be obtained. Rage attacks remain commonly reported but poorly described; their characterization and ontogeny warrant further systematic study. Hypothalamic hamartoma syndrome is a rare disease that is often associated with intractable epileptic encephalopathy and numerous endocrine, cognitive, behavioral, neuropsychological, psychiatric, and psychosocial comorbidities. Given the rarity of the disorder, there has been variable treatment of HH patients across the world. Here, a multidisciplinary group of experts convened from 17 international ILAE level II epilepsy centers to create modified Delphi consensus recommendations on all aspects of the diagnosis and treatment of the HH syndrome: from initial identification of the lesion, medical and surgical recommendations, and the identification and treatment of numerous associated comorbidities. Early consideration of epilepsy surgery should be pursued. These suggestions aggregate broad, intercontinental experience with this rare disease and form the basis for standardizing and improving care for patients affected by HH worldwide. This consensus helps to identify gaps in current evidence. There are various presentations of the HH syndrome and its comorbidities and future multicenter and prospective controlled studies need to be designed to identify and fully address best practices in management, and in particular to identify the best surgical options for patients. Supplementary Material Supplementary Files Round 2 Questions NIHMS2158984-supplement-Supplementary_Files_Round_2_Questions.pdf (61.2KB, pdf) Supplementary Files Round 1 Questions NIHMS2158984-supplement-Supplementary_Files_Round_1_Questions.pdf (206.6KB, pdf) Funding: NTC is funded by NIH/NINDS K23NS131522 and the Hess Foundation. Research reported in this publication was supported by the National Institute Of Neurological Disorders And Stroke of the National Institutes of Health under Award Number K23NS131522. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Management of the European Reference Network for Rare and Complex Epilepsies, ERN EpiCARE is funded by the European Commission. Footnotes Disclosures: N.T. Cohen reports no disclosures. X. Li reports no disclosures. M.M. Berl reports no disclosures. C. Oluigbo reports no disclosures. H. Shirozu reports no disclosures. S.F. Berkovic reports no disclosures. M. Zacharin reports no disclosures. W. Maixner reports no disclosures. A. Schulze-Bonhage reports no disclosures. K. Klotz reports no disclosures. N. Specchio reports no disclosures. S. Ferrand-Sorbets reports no disclosures. C. Bulteau reports no disclosures. A. Arzimanoglou reports no disclosures. J. Regis reports no disclosures. J.H. Cross reports no disclosures. M. Tisdall reports no disclosures. H. Richardson reports no disclosures. A. Cukiert reports no disclosures. C.M. Cukiert reports no disclosures. J. Jacobs-LeVan reports no disclosures. E.J. Donner reports no disclosures. P.L. Pearl reports no disclosures. J.F. Kerrigan reports no disclosures. A. Wilfong reports no disclosures. K.C.J. Yuen reports no disclosures. D. Dlugos reports no disclosures. D.J. Curry reports no disclosures. I. Ali reports no disclosures. J. Ragheb reports no disclosures. L. Soeby reports no disclosures. E. Webster reports no disclosures. W.D. 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Supplementary Materials Supplementary Files Round 2 Questions NIHMS2158984-supplement-Supplementary_Files_Round_2_Questions.pdf (61.2KB, pdf) Supplementary Files Round 1 Questions NIHMS2158984-supplement-Supplementary_Files_Round_1_Questions.pdf (206.6KB, pdf) Data Availability Statement Survey data are available upon reasonable request from a qualified investigator. 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