Dying Before the System Caught Up: A Case of Neurofibromatosis Type 1 in a Geriatric Patient with Pain and Polypharmacy

Dying Before the System Caught Up: A Case of Neurofibromatosis Type 1 in a Geriatric Patient with Pain and Polypharmacy | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Dying Before the System Caught Up: A Case of Neurofibromatosis Type 1 in a Geriatric Patient with Pain and Polypharmacy Irshad Syed, Nitin Thyagaraja, Said Choukri Bendiha, Abdur Rahman Arif, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7490411/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract We present the case of a 72-year-old man with a history of neurofibromatosis type 1 (NF1) who experienced chronic pain, hypotension, and progressive functional decline. His complex medication regimen posed daily management challenges and may have contributed to fluctuations in blood pressure and impaired mobility, which may have impacted his overall clinical stability. This case provides a rare opportunity to examine NF1 in the context of advanced age, a perspective not often explored in case literature as the disease is typically diagnosed and studied in pediatric populations. It illustrates how common geriatric challenges such as polypharmacy, loss of independence, caregiver reliance, and refractory pain can be further complicated by the lifelong burden of a rare genetic condition. Additionally, this case highlights the lack of specific guidelines addressing pain secondary to NF1, and explores the various types of pain associated with the condition. Neurofibromatosis type 1 geriatrics polypharmacy chronic pain DNR end of-life care primary care transitions deprescribing caregiver education medication reconciliation Introduction NF1 affects approximately 1 in 3,000 individuals and is typically diagnosed in childhood.¹ While classical manifestations include cutaneous neurofibromas and neurologic tumors, its impact on aging, chronic pain, and functional capacity in older adults remains sparsely documented. As NF1 patients live longer, geriatricians and primary care providers increasingly encounter the challenges associated with managing late-life complications. This case explores NF1 manifestation in advanced age, addressing the pain associated with the condition and highlighting the need for greater awareness and research to guide optimal care in older adults. Case Presentation Patient: A 72-year-old male with a history of NF1, hypertension, hyperlipidemia, chronic pain syndrome, and past alcohol abuse. He was recently discharged from a skilled nursing facility following a fall and back injury. Social Context: Married, with his spouse serving as the primary caregiver and healthcare surrogate. DNR status was documented. Cognitively intact, yet functionally dependent and wheelchair bound. The patient’s wife managed medication administration but reported confusion regarding the purpose of several medications. Cymbalta (Duloxetine), prescribed for neuropathic pain, had not been administered, and clonidine was understood to be a sleep aid, resulting in it being given more often than prescribed. These factors may have contributed to hypotension and imbalance, increasing the risk of falls. The medication-related issues appear to reflect gaps in discharge counselling and communication from the skilled nursing facility, particularly regarding medication indications and administration guidance given to the family. Clinical Features: ∙ Multiple extensive cutaneous neurofibromas across the body (documented with representative photos) ∙ Kyphosis ∙ PHQ-9 score of 0 ∙ Persistent opioid-refractory pain ∙ Orthostatic hypotension Medications: ∙ Pain: Fentanyl patch, oxycodone PRN, Robaxin ∙Psychotropic: Duloxetine (Cymbalta), Zofran (later discontinued), Clonidine (discontinued due to hypotension) ∙ Chronic conditions: Lisinopril, Lipitor Vital Signs: ∙ Temp: 96.6°F | HR: 68 bpm | BP: 83/56 mmHg | BMI: 25.9 Planned Interventions: ∙ Deprescribing initiated (clonidine and Zofran) ∙ Up-titration of duloxetine for neuropathic pain ∙ Referrals to a pain specialist and for laboratory workup ∙ Continued use of lipid and blood pressure medications pending reassessment Outcome: The patient passed away shortly after re-establishing primary care, before scheduled follow-ups and evaluations could be completed. Discussion This case presents a unique perspective on neurofibromatosis type 1 (NF1) by focusing on an elderly patient, in contrast to the majority of case reports that predominantly describe younger populations. This discussion highlights the typical challenges faced by geriatric patients such as polypharmacy, loss of independent functioning, the need for caregiver support, multidisciplinary care requirements, and debilitation due to refractory pain. These problems are further complicated by the presence of NF1. The central issue specific to NF1 in this patient was refractory pain despite the use of opioid medications. Notably, there are currently no established pain management guidelines specific to geriatric patients with NF1, underscoring a significant gap in the literature and clinical practice. Neuropathic pain is recognized as the most common pain type experienced by patients with NF1. It is often described as burning, shooting, or tingling, resulting from nerve compression and inflammation caused by neurofibromas. Pharmacologic options for neuropathic pain include duloxetine (a serotonin-norepinephrine reuptake inhibitor), pregabalin and gabapentin (anticonvulsants), and tricyclic antidepressants such as amitriptyline. Patients with NF1 may also experience somatic pain, typically due to skeletal deformities such as kyphosis, scoliosis, or pseudoarthrosis. This pain is generally aching, throbbing, and well localized. Management options include acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, naproxen, or meloxicam, and oral opioids (e.g., tramadol, oxycodone, hydrocodone), which provide relief for severe pain but are not recommended for long-term use. Additionally, topical opioids such as fentanyl or buprenorphine patches may be considered. Visceral pain may arise due to large neurofibromas exerting pressure on internal organs. This pain is often described as deep, pressure-like, cramping, and is poorly localized. Treatment options include antispasmodics like hyoscyamine and dicyclomine, anticholinergic agents such as atropine and glycopyrrolate to relax smooth muscles, and calcium channel blockers like nifedipine, which can alleviate pain related to esophageal spasms. Chronic postoperative pain is also a significant concern in NF1 patients following neurofibroma excision. Regional anaesthesia can be employed to manage immediate postoperative pain, while early mobilization and physical therapy may prevent deconditioning. Cognitive behavioural therapy and pain-focused psychotherapy have roles in preventing pain chronification. Overall, NF1 lacks standardized, evidence-based pain management protocols. Consequently, clinicians often rely on general pain guidelines that may inadequately address the unique neurogenic, disfiguring, and psychologically burdensome aspects of NF1-related pain. The limitations of general pain management frameworks in addressing NF1-related pain are summarized in the table below, which compares standard pain management guidelines with the specific challenges encountered in NF1. General Pain Guidelines NF1-Related Pain Challenges Standard opioid escalation models NF1-related pain is often neuropathic or mixed, hence opioids are less effective Dichotomy of acute vs. chronic pain NF1-related pain may be chronic and flaring (e.g., with tumor growth) Focus on degenerative or nociceptive causes NF1 involves nerve tumors, plexiform involvement, and bone deformity Neuropathic pain addressed mostly in the context of diabetes and multiple sclerosis NF1-related neuropathic pain is under-recognized and under-addressed This case also serves as a reminder that NF1 is not exclusively a pediatric disorder. With improvements in quality of care and increasing longevity, older adults with NF1 present new clinical challenges, including managing complex, lifelong disease manifestations in the context of aging. NF1 is an autosomal dominant neurocutaneous disorder characterized by variable expressivity and complete penetrance, resulting in heterogeneous disease severity. In this patient, cutaneous neurofibromas caused severe radiating pain throughout the body. Caregiver availability and training emerged as critical factors in managing the patient’s complex needs, especially given the opioid-refractory nature of NF1-related pain and the necessity for optimized use of neuropathic pain medications. Effective coordination among multidisciplinary teams, including primary care, pain medicine, and palliative care, is essential to facilitate smooth care transitions, minimize referral delays, and implement deprescribing strategies where appropriate. Medication management in this patient was complicated by the need to maintain consistency across care settings and by overlapping chronic medical conditions common in older adults. Miscommunication regarding the medication regimen during skilled nursing facility discharge likely contributed to the overuse of clonidine, resulting in hypotension and increased fall risk. This highlights the ongoing importance of regular medication reconciliation, clear communication, and education for both patients and caregivers to ensure safe and effective care. Literature Comparison: Previous literature on NF1 has predominantly focused on manifestations in childhood and early adulthood, particularly in relation to tumor development and genetic counseling 1 , 2 , 3 and genetic complexities 4 . However, data on NF1 in older adults remain limited. Case studies in geriatric NF1 populations tend to focus on malignancy surveillance or vestibular complications rather than polypharmacy, chronic pain, caregiver challenges, or care transitions 5 . Clinical Takeaways: Older adults with NF1 require proactive integration into primary and geriatric care systems. ∙ Cutaneous neurofibromas, though non-malignant, can result in significant functional impairment and chronic pain. ∙ Aggressive attention to polypharmacy and caregiver education is crucial, especially during care transitions. ∙ Tools like the PHQ-9 may underestimate suffering in patients where physical pain is predominant. ∙ Advance care planning and palliative discussions should be initiated early in complex, chronic syndromic diseases. ∙ Medication reconciliation and caregiver support play vital roles in preventing iatrogenic harm and improving patient outcomes. Clear instructions and education for caregivers on medication administration are essential to ensure proper adherence and avoid complications. Declarations Competing interests: The authors declare no conflicts of interest. Ethics approval of the Institutional IRB: This case report was conducted in accordance with institutional guidelines. Per our institution’s policy, case reports involving a single patient are exempt from formal IRB review. Consent to participate: Written informed consent to participate in this case report was obtained from the patient’s wife. Consent for publication: Written informed consent for publication of the case details and accompanying images was obtained from the patient’s next of kin. Funding: This research received no external funding. Availability of data and materials: Data sharing is not applicable to this article as no datasets were generated or analyzed. Authors contributions: I.S.: Primary care family medicine doctor who supervised the patient’s care, provided overall clinical guidance, and critically reviewed the manuscript. N.T.: Observer at the clinic, contributed to clinical data collection, case analysis, manuscript drafting, and served as corresponding author. C.S.B.: Observer at the clinic, assisted with patient history review, literature search, and manuscript drafting. A.R.A.: Physician assistant who participated in patient management, contributed clinical insights, and reviewed the manuscript for accuracy. S.A.: Physician assistant who assisted in patient care, coordinated follow-up details, and contributed to manuscript editing and final review. All authors read and approved of the final manuscript. Acknowledgements: We thank the patient and his family for their cooperation and consent, and the healthcare staff involved in the patient’s care for their support. References Ferner RE, Huson SM, Thomas N, et al. Guidelines for the diagnosis and management of individuals with neurofibromatosis 1. J Med Genet. 2007;44(2):81–88. Duong TA, Sbidian E, Valeyrie-Allanore L, et al. Mortality associated with neurofibromatosis 1: a cohort study of 1895 patients in 1980–2006 in France. Orphanet J Rare Dis. 2011; 6:18. Hirbe AC, Gutmann DH. Neurofibromatosis type 1: a multidisciplinary approach to care. Lancet Neurol. 2014;13(8):834–843. Upadhyaya M, Spurlock G, Thomas L, et al. Microarray-based copy number analysis of neurofibromatosis type-1 (NF1)-associated malignant peripheral nerve sheath tumors reveals novel genes and genomic imbalances. Hum Genomics. 2012; 6:23. Salazar R, Mendez L, Acosta M. Geriatric considerations in rare hereditary disorders: transitioning care in older adults with neurofibromatosis type 1. Clin Geriatr Med. 2020;36(2):331–342. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7490411","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":510418998,"identity":"fa7624e9-3480-45a3-8174-9a69ec72b416","order_by":0,"name":"Irshad Syed","email":"","orcid":"","institution":"Marietta Family Medicine","correspondingAuthor":false,"prefix":"","firstName":"Irshad","middleName":"","lastName":"Syed","suffix":""},{"id":510419001,"identity":"8d2f8334-32f0-42af-8a3f-509c9e7491cb","order_by":1,"name":"Nitin Thyagaraja","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8klEQVRIie3PsUoDMRzH8V/4w/8c0rrq0r5CRFAPFJ+lFDpV6Bt4cHAuUdc6+QwuN18IuPoAWQp9gSsuRyloelK3XjMK5juEP+H/IQSIxf5iBFRoeOBHUdX+5OQgIVRC98/BgJlvCYU8Ax6MMk+s3F10dZkcGzuTFyIbamWv1+WwTxD1arqfpDnBzq8mBJbK3j25s4JApy/lfqKsJ1K+8w/RTnjC1DtI+Eu2JNXuNpTwSUvQuFEIUbanWTFPZuYxc+OCRN79lw+z/JQN3z+TfVs0G3fz+pCbetVBfmMcKYhiO4osYL8tWQCb0OVYLBb7T30DpyBJ6bI+rIYAAAAASUVORK5CYII=","orcid":"","institution":"Marietta Family Medicine","correspondingAuthor":true,"prefix":"","firstName":"Nitin","middleName":"","lastName":"Thyagaraja","suffix":""},{"id":510419002,"identity":"560fb92e-d200-4266-bcf2-0452a73e0206","order_by":2,"name":"Said Choukri Bendiha","email":"","orcid":"","institution":"Marietta Family Medicine","correspondingAuthor":false,"prefix":"","firstName":"Said","middleName":"Choukri","lastName":"Bendiha","suffix":""},{"id":510419004,"identity":"72d602a4-104d-49a9-812c-4c0272a80818","order_by":3,"name":"Abdur Rahman Arif","email":"","orcid":"","institution":"Marietta Family Medicine","correspondingAuthor":false,"prefix":"","firstName":"Abdur","middleName":"Rahman","lastName":"Arif","suffix":""},{"id":510419006,"identity":"7d5537b4-b8ff-4688-9721-73bac5588a17","order_by":4,"name":"Shopno Ahmed","email":"","orcid":"","institution":"Marietta Family Medicine","correspondingAuthor":false,"prefix":"","firstName":"Shopno","middleName":"","lastName":"Ahmed","suffix":""}],"badges":[],"createdAt":"2025-08-29 16:38:30","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7490411/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7490411/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":90853966,"identity":"93f49106-ef17-4ee3-84c1-f05f63e67096","added_by":"auto","created_at":"2025-09-09 04:03:22","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":431748,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7490411/v1/d4cc2a6b-6acc-49a4-8a0a-c8d323b6e942.pdf"},{"id":90853767,"identity":"6c1d2178-5761-4203-af70-73260bb9a005","added_by":"auto","created_at":"2025-09-09 03:55:18","extension":"jpg","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":166707,"visible":true,"origin":"","legend":"","description":"","filename":"IMG20250319WA00071.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7490411/v1/7dbee9875ac021f61abe62a8.jpg"},{"id":90853760,"identity":"b72c2dd3-de90-42e7-b761-4e22af259a81","added_by":"auto","created_at":"2025-09-09 03:55:18","extension":"jpg","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":154091,"visible":true,"origin":"","legend":"","description":"","filename":"IMG20250319WA00081.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7490411/v1/8aee556b61e2e3af92623fa0.jpg"}],"financialInterests":"No competing interests reported.","formattedTitle":"Dying Before the System Caught Up: A Case of Neurofibromatosis Type 1 in a Geriatric Patient with Pain and Polypharmacy","fulltext":[{"header":"Introduction","content":"\u003cp\u003eNF1 affects approximately 1 in 3,000 individuals and is typically diagnosed in childhood.\u0026sup1; While classical manifestations include cutaneous neurofibromas and neurologic tumors, its impact on aging, chronic pain, and functional capacity in older adults remains sparsely documented. As NF1 patients live longer, geriatricians and primary care providers increasingly encounter the challenges associated with managing late-life complications. This case explores NF1 manifestation in advanced age, addressing the pain associated with the condition and highlighting the need for greater awareness and research to guide optimal care in older adults.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003e\u003cstrong\u003ePatient: \u0026nbsp;\u003c/strong\u003eA 72-year-old male with a history of NF1, hypertension, hyperlipidemia, chronic pain syndrome, and past alcohol abuse. He was recently discharged from a skilled nursing facility following a fall and back injury.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSocial Context:\u003c/strong\u003e Married, with his spouse serving as the primary caregiver and healthcare surrogate. DNR status was documented. Cognitively intact, yet functionally dependent and wheelchair bound. The patient\u0026rsquo;s wife managed medication administration but reported confusion regarding the purpose of several medications. Cymbalta (Duloxetine), prescribed for neuropathic pain, had not been administered, and clonidine was understood to be a sleep aid, resulting in it being given more often than prescribed. These factors may have contributed to hypotension and imbalance, increasing the risk of falls. The medication-related issues appear to reflect gaps in discharge counselling and communication from the skilled nursing facility, particularly regarding medication indications and administration guidance given to the family.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Features:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e∙ Multiple extensive cutaneous neurofibromas across the body (documented with \u0026nbsp;representative photos)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e∙ Kyphosis\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e∙ PHQ-9 score of 0\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e∙ Persistent opioid-refractory pain\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e∙ Orthostatic hypotension\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMedications:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e∙ Pain: Fentanyl patch, oxycodone PRN, Robaxin\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e∙Psychotropic: Duloxetine (Cymbalta), Zofran (later discontinued), Clonidine \u0026nbsp;(discontinued due to hypotension)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e∙ Chronic conditions: Lisinopril, Lipitor\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eVital Signs:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e∙ Temp: 96.6\u0026deg;F | HR: 68 bpm | BP: 83/56 mmHg | BMI: 25.9\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePlanned Interventions:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e∙ Deprescribing initiated (clonidine and Zofran)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e∙ Up-titration of duloxetine for neuropathic pain\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e∙ Referrals to a pain specialist and for laboratory workup\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e∙ Continued use of lipid and blood pressure medications pending reassessment\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOutcome:\u003c/strong\u003e The patient passed away shortly after re-establishing primary care, before \u0026nbsp;scheduled follow-ups and evaluations could be completed.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis case presents a unique perspective on neurofibromatosis type 1 (NF1) by focusing on an elderly patient, in contrast to the majority of case reports that predominantly describe younger populations. This discussion highlights the typical challenges faced by geriatric patients such as polypharmacy, loss of independent functioning, the need for caregiver support, multidisciplinary care requirements, and debilitation due to refractory pain. These problems are further complicated by the presence of NF1.\u003c/p\u003e\u003cp\u003eThe central issue specific to NF1 in this patient was refractory pain despite the use of opioid medications. Notably, there are currently no established pain management guidelines specific to geriatric patients with NF1, underscoring a significant gap in the literature and clinical practice.\u003c/p\u003e\u003cp\u003eNeuropathic pain is recognized as the most common pain type experienced by patients with NF1. It is often described as burning, shooting, or tingling, resulting from nerve compression and inflammation caused by neurofibromas. Pharmacologic options for neuropathic pain include duloxetine (a serotonin-norepinephrine reuptake inhibitor), pregabalin and gabapentin (anticonvulsants), and tricyclic antidepressants such as amitriptyline.\u003c/p\u003e\u003cp\u003ePatients with NF1 may also experience somatic pain, typically due to skeletal deformities such as kyphosis, scoliosis, or pseudoarthrosis. This pain is generally aching, throbbing, and well localized. Management options include acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, naproxen, or meloxicam, and oral opioids (e.g., tramadol, oxycodone, hydrocodone), which provide relief for severe pain but are not recommended for long-term use. Additionally, topical opioids such as fentanyl or buprenorphine patches may be considered.\u003c/p\u003e\u003cp\u003eVisceral pain may arise due to large neurofibromas exerting pressure on internal organs. This pain is often described as deep, pressure-like, cramping, and is poorly localized. Treatment options include antispasmodics like hyoscyamine and dicyclomine, anticholinergic agents such as atropine and glycopyrrolate to relax smooth muscles, and calcium channel blockers like nifedipine, which can alleviate pain related to esophageal spasms.\u003c/p\u003e\u003cp\u003eChronic postoperative pain is also a significant concern in NF1 patients following neurofibroma excision. Regional anaesthesia can be employed to manage immediate postoperative pain, while early mobilization and physical therapy may prevent deconditioning. Cognitive behavioural therapy and pain-focused psychotherapy have roles in preventing pain chronification.\u003c/p\u003e\u003cp\u003eOverall, NF1 lacks standardized, evidence-based pain management protocols. Consequently, clinicians often rely on general pain guidelines that may inadequately address the unique neurogenic, disfiguring, and psychologically burdensome aspects of NF1-related pain. The limitations of general pain management frameworks in addressing NF1-related pain are summarized in the table below, which compares standard pain management guidelines with the specific challenges encountered in NF1.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGeneral Pain Guidelines\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNF1-Related Pain Challenges\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStandard opioid escalation models\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNF1-related pain is often neuropathic or mixed, hence opioids are less effective\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDichotomy of acute vs.\u0026nbsp;chronic pain\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNF1-related pain may be chronic and flaring (e.g., with tumor growth)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFocus on degenerative or nociceptive causes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNF1 involves nerve tumors, plexiform involvement, and bone deformity\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeuropathic pain addressed mostly in the context of diabetes and multiple sclerosis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNF1-related neuropathic pain is under-recognized and under-addressed\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThis case also serves as a reminder that NF1 is not exclusively a pediatric disorder. With improvements in quality of care and increasing longevity, older adults with NF1 present new clinical challenges, including managing complex, lifelong disease manifestations in the context of aging. NF1 is an autosomal dominant neurocutaneous disorder characterized by variable expressivity and complete penetrance, resulting in heterogeneous disease severity. In this patient, cutaneous neurofibromas caused severe radiating pain throughout the body.\u003c/p\u003e\u003cp\u003eCaregiver availability and training emerged as critical factors in managing the patient\u0026rsquo;s complex needs, especially given the opioid-refractory nature of NF1-related pain and the necessity for optimized use of neuropathic pain medications. Effective coordination among multidisciplinary teams, including primary care, pain medicine, and palliative care, is essential to facilitate smooth care transitions, minimize referral delays, and implement deprescribing strategies where appropriate.\u003c/p\u003e\u003cp\u003eMedication management in this patient was complicated by the need to maintain consistency across care settings and by overlapping chronic medical conditions common in older adults. Miscommunication regarding the medication regimen during skilled nursing facility discharge likely contributed to the overuse of clonidine, resulting in hypotension and increased fall risk. This highlights the ongoing importance of regular medication reconciliation, clear communication, and education for both patients and caregivers to ensure safe and effective care.\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eLiterature Comparison:\u003c/h2\u003e\u003cp\u003ePrevious literature on NF1 has predominantly focused on manifestations in childhood and early adulthood, particularly in relation to tumor development and genetic counseling \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e and genetic complexities \u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. However, data on NF1 in older adults remain limited. Case studies in geriatric NF1 populations tend to focus on malignancy surveillance or vestibular complications rather than polypharmacy, chronic pain, caregiver challenges, or care transitions\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eClinical Takeaways:\u003c/h3\u003e\n\u003cp\u003eOlder adults with NF1 require proactive integration into primary and geriatric care systems.\u003c/p\u003e\u003cp\u003e∙ Cutaneous neurofibromas, though non-malignant, can result in significant functional impairment and chronic pain.\u003c/p\u003e\u003cp\u003e∙ Aggressive attention to polypharmacy and caregiver education is crucial, especially during care transitions.\u003c/p\u003e\u003cp\u003e∙ Tools like the PHQ-9 may underestimate suffering in patients where physical pain is predominant.\u003c/p\u003e\u003cp\u003e∙ Advance care planning and palliative discussions should be initiated early in complex, chronic syndromic diseases.\u003c/p\u003e\u003cp\u003e∙ Medication reconciliation and caregiver support play vital roles in preventing iatrogenic harm and improving patient outcomes. Clear instructions and education for caregivers on medication administration are essential to ensure proper adherence and avoid complications.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e The authors declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval of the Institutional IRB:\u003c/strong\u003e This case report was conducted in accordance with institutional guidelines. Per our institution\u0026rsquo;s policy, case reports involving a single patient are exempt from formal IRB review.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate:\u003c/strong\u003e Written informed consent to participate in this case report was obtained from the patient\u0026rsquo;s wife.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u003c/strong\u003e Written informed consent for publication of the case details and accompanying images was obtained from the patient\u0026rsquo;s next of kin.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e This research received no external funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u003c/strong\u003e Data sharing is not applicable to this article as no datasets were generated or analyzed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors contributions:\u003c/strong\u003e I.S.: Primary care family medicine doctor who supervised the patient\u0026rsquo;s care, provided overall clinical guidance, and critically reviewed the manuscript.\u003c/p\u003e\n\u003cp\u003eN.T.: Observer at the clinic, contributed to clinical data collection, case analysis, manuscript drafting, and served as corresponding author.\u003c/p\u003e\n\u003cp\u003eC.S.B.: Observer at the clinic, assisted with patient history review, literature search, and manuscript drafting.\u003c/p\u003e\n\u003cp\u003eA.R.A.: Physician assistant who participated in patient management, contributed clinical insights, and reviewed the manuscript for accuracy.\u003c/p\u003e\n\u003cp\u003eS.A.: Physician assistant who assisted in patient care, coordinated follow-up details, and contributed to manuscript editing and final review.\u003c/p\u003e\n\u003cp\u003eAll authors read and approved of the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u003c/strong\u003e We thank the patient and his family for their cooperation and consent, and the healthcare staff involved in the patient\u0026rsquo;s care for their support.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eFerner RE, Huson SM, Thomas N, et al. Guidelines for the diagnosis and management of individuals with neurofibromatosis 1. J Med Genet. 2007;44(2):81\u0026ndash;88.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDuong TA, Sbidian E, Valeyrie-Allanore L, et al. Mortality associated with neurofibromatosis 1: a cohort study of 1895 patients in 1980\u0026ndash;2006 in France. Orphanet J Rare Dis. 2011; 6:18.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHirbe AC, Gutmann DH. Neurofibromatosis type 1: a multidisciplinary approach to care. Lancet Neurol. 2014;13(8):834\u0026ndash;843.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eUpadhyaya M, Spurlock G, Thomas L, et al. Microarray-based copy number analysis of neurofibromatosis type-1 (NF1)-associated malignant peripheral nerve sheath tumors reveals novel genes and genomic imbalances. Hum Genomics. 2012; 6:23.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSalazar R, Mendez L, Acosta M. Geriatric considerations in rare hereditary disorders: transitioning care in older adults with neurofibromatosis type 1. Clin Geriatr Med. 2020;36(2):331\u0026ndash;342.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-rare-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Journal of Rare Diseases](https://link.springer.com/journal/44162)","snPcode":"44162","submissionUrl":"https://submission.nature.com/new-submission/44162/3","title":"Journal of Rare Diseases","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Open","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Neurofibromatosis type 1, geriatrics, polypharmacy, chronic pain, DNR, end of-life care, primary care transitions, deprescribing, caregiver education, medication reconciliation","lastPublishedDoi":"10.21203/rs.3.rs-7490411/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7490411/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eWe present the case of a 72-year-old man with a history of neurofibromatosis type 1 (NF1) who experienced chronic pain, hypotension, and progressive functional decline. His complex medication regimen posed daily management challenges and may have contributed to fluctuations in blood pressure and impaired mobility, which may have impacted his overall clinical stability.\u003c/p\u003e\u003cp\u003eThis case provides a rare opportunity to examine NF1 in the context of advanced age, a perspective not often explored in case literature as the disease is typically diagnosed and studied in pediatric populations. It illustrates how common geriatric challenges such as polypharmacy, loss of independence, caregiver reliance, and refractory pain can be further complicated by the lifelong burden of a rare genetic condition. Additionally, this case highlights the lack of specific guidelines addressing pain secondary to NF1, and explores the various types of pain associated with the condition.\u003c/p\u003e","manuscriptTitle":"Dying Before the System Caught Up: A Case of Neurofibromatosis Type 1 in a Geriatric Patient with Pain and Polypharmacy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-09 03:55:13","doi":"10.21203/rs.3.rs-7490411/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2025-11-05T15:54:20+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-23T00:43:22+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"250785642659166046968800522029987417511","date":"2025-10-14T01:25:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"192765320220050625265655028734463127382","date":"2025-10-08T03:45:13+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-09T11:33:04+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-09-09T06:39:49+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Rare Diseases","date":"2025-09-04T19:09:33+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-rare-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Journal of Rare Diseases](https://link.springer.com/journal/44162)","snPcode":"44162","submissionUrl":"https://submission.nature.com/new-submission/44162/3","title":"Journal of Rare Diseases","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Open","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d1c774d5-e546-42fa-8a06-942194329db2","owner":[],"postedDate":"September 9th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-11-05T19:38:17+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-09 03:55:13","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7490411","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7490411","identity":"rs-7490411","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}