Stimulant Treatment of Emergent ADHD Phenotype in Adolescent Batten Disease: A Case Report

Stimulant Treatment of Emergent ADHD Phenotype in Adolescent Batten Disease: A Case Report | 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 Stimulant Treatment of Emergent ADHD Phenotype in Adolescent Batten Disease: A Case Report Daniel You, Micah Boerma This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8643968/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 13 You are reading this latest preprint version Abstract Background: Neuronal ceroid lipofuscinosis type 3 (CLN3), also known as juvenile Batten disease, is a rare neurodegenerative disorder characterised by progressive visual loss, cognitive decline, and behavioural disturbance. Neuropsychiatric symptoms are common and are generally attributed to global neurodegeneration. Secondary attention-deficit/hyperactivity disorder (ADHD)—the emergence of ADHD symptoms following the onset of a neurological condition—has not previously been reported in CLN3. Nor has stimulant treatment of secondary ADHD in CLN3 been previously reported. Case presentation : We describe a 15-year-old boy with CLN3 who developed progressive inattention, impulsivity, emotional dysregulation, and behavioural aggression during early adolescence, in the absence of any childhood history consistent with primary ADHD. Neuropsychological assessment demonstrated evidence of reduced cognitive ability with disproportionate impairment in attention, working memory, and executive functioning. By age 13 his symptoms caused significant impairment across home and school settings. A diagnosis of secondary ADHD associated with CLN3 was made. Treatment with methylphenidate resulted in marked improvements in attention, aggression, school engagement, and had good tolerability. Conclusions: This case highlights a previously unreported presentation of secondary ADHD in CLN3 and demonstrates that stimulant treatment may be effective in selected adolescents with this condition. Clinicians should be alert to the possibility of treatable secondary ADHD in CLN3. Batten disease CLN3 secondary ADHD neurodegenerative disorders stimulant treatment adolescent psychiatry Background Neuronal ceroid lipofuscinosis type 3 (CLN3), also known as juvenile Batten disease, is a rare autosomal recessive neurodegenerative disorder due to a mutation in the CLN3 gene which encodes a ubiquitous protein involved in many cellular processes including membrane fusion, vesicular transport, autophagy, and apoptosis ( 1 ). It usually presents in primary school-aged children with progressive visual impairment, followed by behavioural disturbance and cognitive decline after several years. Sleep problems, motor symptoms and epilepsy also often occur at a later stage ( 2 ). The disease progresses to difficulty with chewing and swallowing, disabling involuntary movements, and cardiac involvement. Death most commonly occurs in the 20s ( 1 ). The neurodevelopmental profile prior to the onset of visual impairment in Batten disease is thought to be normal. Cognitive decline and behavioural difficulties are well recognised in CLN3 and usually occur several years after visual impairment. Cognitive domains initially affected include comprehension, short-term memory and attention ( 1 ). Emotional and behavioural difficulties reported include anxiety, depressed mood, aggression, and psychotic symptoms3). These tend to emerge early in the disease course, worsen during the years following diagnosis, and become less pronounced as general function declines ( 1 ). The behavioural disturbance represents a major challenge to quality of life for patients and families, particularly given the relatively slow disease progression ( 4 ). Although impairment with inattention, dysregulation, and aggression is frequently described in CLN3, the existing literature has not previously reported or conceptualised these as secondary attention-deficit/hyperactivity disorder (ADHD). Secondary ADHD is a clinical construct describing the emergence of ADHD symptoms following the onset of a medical or neurological condition (5; 6). It has primarily been described in association with acquired brain injury and epilepsy and some other neurological disorders (5; 7). Whilst there is growing evidence supporting the use of stimulants in secondary ADHD ( 7 ), particularly for attentional difficulties, there is none published regarding stimulant use in cognitive difficulties associated with CLN3. Here we report a case of CLN3 with prominent executive dysfunction, impulsivity, and dysregulation that was novelly conceptualised as ADHD secondary to the underlying neurodegenerative disorder. The patient showed a clinically meaningful response to stimulants, a treatment already successfully used for secondary ADHD associated with other pathologies. There was a clinically meaningful response to stimulant treatment that has been used successfully in secondary ADHD associated with other pathologies. Case Presentation Elmond is a 15-year-old boy with CLN3 who was referred to consultation-liaison psychiatry with a two-year history of worsening behavioural dysregulation, inattention, impulsivity, and aggression. Elmond is the third of four children, all of whom live at home with both parents. His eldest sister also has CLN3, while his other siblings are unaffected. He attends a mainstream secondary school with significant educational supports. He has a stable peer group, is actively involved in music and religious activities, and benefits from a trained therapy dog that assists with emotional regulation and sleep. Infancy, childhood history, and developmental milestones were unremarkable. There was no history of attentional difficulties, hyperactivity, impulsivity, or behavioural dysregulation in early or middle childhood, and no concerns suggestive of a primary neurodevelopmental disorder. Elmond was diagnosed with CLN3 at age 8 via genetic testing, following the diagnosis of the same neurodegenerative disorder as his sister after she developed symptoms. From 10 age 10, he developed progressive visual impairment affecting night vision, depth perception, and peripheral vision. By age 12, this limited participation in sports. He also developed learning difficulties, requiring classroom aide supports and visual assistance within a mainstream school setting, including the use of a computer for all reading. From late childhood, he experienced sleep onset difficulties that improved with melatonin, as well as intermittent behavioural outbursts characterised by irritability and emotional lability. Anxiety symptoms emerged around age 12 and were managed with community-based psychological therapy. From age 12, he developed intermittent involuntary movements including head shaking, shoulder shrugging, and complex motor behaviours. Video EEG recordings demonstrated no epileptiform activity, and these events were characterised as complex motor tics. Neuroimaging identified a mild Chiari I malformation, yet remained seizure-free. Between ages 13 and 15, there was a progressive deterioration in attention, working memory, dysregulation, and increasing fatigue. During this period, behavioural outbursts escalated in frequency and intensity, at times involving physical aggression toward family members, followed by remorse or denial. School participation became increasingly challenging with reported memory and attentional difficulties and difficulties retaining learned material. The symptoms worsened throughout the day due to progressive fatigue, typically peaking once the school day ended Neuropsychological assessment at age 13 demonstrated low-average intellectual functioning with academic skills below grade level. Repeat assessment at age 15 demonstrated a stable overall cognitive profile with impairment in working memory, attention, and executive functioning. Standardised questionnaires completed by parents and teachers indicated clinically significant symptoms of ADHD across home and school settings. At age 15, he was referred to consultation-liaison psychiatry. Psychiatric assessment identified symptoms of inattention, impulsivity, and emotional dysregulation across multiple settings. There was no evidence of childhood-onset ADHD or family history of the disorder. His presentation was conceptualised as ADHD secondary to the CLN3, with contributory factors including disease-associated fatigue and insomnia, emotional adjustment to chronic illness, and carer burden for 2 children with neurodegenerative disease. After limited effectiveness of psychological interventions for emotional dysregulation, a trial of methylphenidate was commenced at age 15 years and 6 months. Both Elmond and his parents reported marked improvements in attention, emotional and behavioural regulation, mood stability, family functioning, and school engagement. He reported improved concentration and reduced irritability. The medication was well tolerated, with manageable appetite suppression and no clinically significant worsening of sleep or involuntary movements. With improvement in mood and attention, Elmond and his family were able to engage meaningfully in concurrent psychological interventions. These sessions addressed family relationship and adjusting to his degenerative disease, emphasising a values-driven approach to living. Liaison with Elmond’s school led to specific educational adjustments to support the secondary ADHD diagnosis. Discussion and Conclusions This case report is the first to describe the conceptualisation and management of a specific cluster of behavioural difficulties in a patient with CLN3, as secondary ADHD. Behavioural and emotional disturbance is well documented in CLN3 and is recognised as a major contributor to reduced quality of life for patients and families ( 2 , 4 ). However, the literature typically describes these difficulties in non-specific terms such as irritability or behavioural problems. This case report highlights that such symptoms may cluster into a recognisable and clinically meaningful syndrome consistent with secondary ADHD. In this case, formal psychiatric assessment and neuropsychological testing demonstrated cross setting impairment, prominent executive dysfunction, and working memory limitations, supporting this formulation. Notably, the patient demonstrated a marked and sustained response to stimulant treatment with improvements in attention, behavioural regulation, emotional stability, school engagement, and family functioning. This raises the possibility that stimulant treatment may be effective in addressing similar behavioural phenotypes in CLN3, as has been shown in other neurological pathologies with secondary ADHD. This conceptual framework also supports the use of tailored non-pharmacological interventions which are commonly used to support children with ADHD, including school liaison, behavioural supports, and educational accommodations. The introduction of stimulant medication supported Elmond’s engagement in psychological therapy and his schooling. Beyond addressing frequent behavioural escalations, Elmond was able to engage meaningfully in dialogue about how he understands his CLN3 diagnosis, how it affects him, what he can control in his life and what he cannot, and how he can act in accordance with his values. This case highlights how recognising this phenotype may facilitate targeted pharmacological and non-pharmacological interventions, with the potential to significantly improve quality of life and outcomes for adolescents living with juvenile Batten disease. While the generalisability of a single case report is inherently constrained, this framework for CLN3 associated secondary ADHD, and the observed efficacy of stimulant therapy, provides impetus for further case series and research into the management of phenotypes in CLN3. Abbreviations ADHD Attention deficit hyperactivity disorder CLN3 Neuronal ceroid lipofuscinosis type 3 EEG Electroencephalogram Declarations Ethics Approval and Consent to Participate Ethics approval was obtained from the Sydney Children’s Hospital Network Human Research Ethics Committee. Written informed consent to participate was obtained from the patient’s parent. Consent for publication Written informed consent for publication, including of clinical details, was obtained from the patient’s parent. Competing interests No potential conflict of interest is known by the authors. Funding No specific funding was received for this work. Author Contribution DY and MB reviewed the patient data and notes, clinical progress and management. DY prepared the initial manuscript draft. DY and MB contributed significant editing and review of the manuscript. All authors read and approved the final manuscript. Data Availability Materials are available from the corresponding author on request. References Ostergaard JR. Juvenile neuronal ceroid lipofuscinosis (Batten disease): current insights. Degener Neurol Neuromuscul Dis. 2016;6:73–83. 10.2147/DNND.S111967 . Adams HR, Mink JW, University of Rochester Batten Center Study Group. Neurobehavioral features and natural history of juvenile neuronal ceroid lipofuscinosis (Batten disease). J Child Neurol. 2013;28(9):1128–36. 10.1177/0883073813494813 . Honingh AK, Kruithof YL, Kuper WF, van Hasselt PM, Sterkenburg PS. Towards understanding behaviour and emotions of children with CLN3 disease (Batten disease): patterns, problems and support for child and family. Int J Environ Res Public Health. 2022;19(10):5895. 10.3390/ijerph19105895 . Krantz M, Malm E, Darin N, Sofou K, Savvidou A, Reilly C, et al. Parental experiences of having a child with CLN3 disease (juvenile Batten disease) and how these experiences relate to family resilience. Child Care Health Dev. 2022;48(5):842–51. 10.1111/cch.12993 . Asarnow RF, Newman N, Weiss RE, Su E. Association of attention-deficit/hyperactivity disorder diagnoses with pediatric traumatic brain injury: a meta-analysis. JAMA Pediatr. 2021;175(10):1009–16. 10.1001/jamapediatrics.2021.2033 . Stojanovski S, Scratch SE, Dunkley BT, Schachar R, Wheeler AL. A systematic scoping review of new attention problems following traumatic brain injury in children. Front Neurol. 2021;12:751736. 10.3389/fneur.2021.751736 . Pitt-Francis A, Stevens AR, Ahmed Z, Di Pietro V. The use of methylphenidate to improve executive functioning in pediatric traumatic brain injury: a systematic review and meta-analysis. Trauma Care. 2024;5(1):1. 10.3390/traumacare5010001 . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 08 Mar, 2026 Reviews received at journal 06 Mar, 2026 Reviewers agreed at journal 26 Feb, 2026 Reviewers agreed at journal 26 Feb, 2026 Reviews received at journal 25 Feb, 2026 Reviews received at journal 17 Feb, 2026 Reviewers agreed at journal 17 Feb, 2026 Reviewers agreed at journal 17 Feb, 2026 Reviewers invited by journal 17 Feb, 2026 Editor assigned by journal 17 Feb, 2026 Editor invited by journal 27 Jan, 2026 Submission checks completed at journal 23 Jan, 2026 First submitted to journal 23 Jan, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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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-8643968","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":595169128,"identity":"ae535c6a-04e9-45ae-a348-62c561a649e8","order_by":0,"name":"Daniel You","email":"data:image/png;base64,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","orcid":"","institution":"The University of Sydney","correspondingAuthor":true,"prefix":"","firstName":"Daniel","middleName":"","lastName":"You","suffix":""},{"id":595169130,"identity":"0837adb7-3ae1-40d3-887e-949e3e8280a3","order_by":1,"name":"Micah Boerma","email":"","orcid":"","institution":"University of Southern Queensland","correspondingAuthor":false,"prefix":"","firstName":"Micah","middleName":"","lastName":"Boerma","suffix":""}],"badges":[],"createdAt":"2026-01-20 02:23:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8643968/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8643968/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":103213789,"identity":"fc8099fd-ba32-44b6-98b4-5336626dc53b","added_by":"auto","created_at":"2026-02-23 09:06:42","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":307121,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8643968/v1/81e2548d-8e8d-4058-a283-4272c9f8bbbd.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Stimulant Treatment of Emergent ADHD Phenotype in Adolescent Batten Disease: A Case Report","fulltext":[{"header":"Background","content":"\u003cp\u003eNeuronal ceroid lipofuscinosis type 3 (CLN3), also known as juvenile Batten disease, is a rare autosomal recessive neurodegenerative disorder due to a mutation in the \u003cem\u003eCLN3\u003c/em\u003e gene which encodes a ubiquitous protein involved in many cellular processes including membrane fusion, vesicular transport, autophagy, and apoptosis (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). It usually presents in primary school-aged children with progressive visual impairment, followed by behavioural disturbance and cognitive decline after several years. Sleep problems, motor symptoms and epilepsy also often occur at a later stage (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). The disease progresses to difficulty with chewing and swallowing, disabling involuntary movements, and cardiac involvement. Death most commonly occurs in the 20s (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). The neurodevelopmental profile prior to the onset of visual impairment in Batten disease is thought to be normal.\u003c/p\u003e \u003cp\u003eCognitive decline and behavioural difficulties are well recognised in CLN3 and usually occur several years after visual impairment. Cognitive domains initially affected include comprehension, short-term memory and attention (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Emotional and behavioural difficulties reported include anxiety, depressed mood, aggression, and psychotic symptoms3). These tend to emerge early in the disease course, worsen during the years following diagnosis, and become less pronounced as general function declines (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). The behavioural disturbance represents a major challenge to quality of life for patients and families, particularly given the relatively slow disease progression (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAlthough impairment with inattention, dysregulation, and aggression is frequently described in CLN3, the existing literature has not previously reported or conceptualised these as secondary attention-deficit/hyperactivity disorder (ADHD). Secondary ADHD is a clinical construct describing the emergence of ADHD symptoms following the onset of a medical or neurological condition (5; 6). It has primarily been described in association with acquired brain injury and epilepsy and some other neurological disorders (5; 7). Whilst there is growing evidence supporting the use of stimulants in secondary ADHD (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e), particularly for attentional difficulties, there is none published regarding stimulant use in cognitive difficulties associated with CLN3.\u003c/p\u003e \u003cp\u003eHere we report a case of CLN3 with prominent executive dysfunction, impulsivity, and dysregulation that was novelly conceptualised as ADHD secondary to the underlying neurodegenerative disorder. The patient showed a clinically meaningful response to stimulants, a treatment already successfully used for secondary ADHD associated with other pathologies. There was a clinically meaningful response to stimulant treatment that has been used successfully in secondary ADHD associated with other pathologies.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eElmond is a 15-year-old boy with CLN3 who was referred to consultation-liaison psychiatry with a two-year history of worsening behavioural dysregulation, inattention, impulsivity, and aggression. Elmond is the third of four children, all of whom live at home with both parents. His eldest sister also has CLN3, while his other siblings are unaffected. He attends a mainstream secondary school with significant educational supports. He has a stable peer group, is actively involved in music and religious activities, and benefits from a trained therapy dog that assists with emotional regulation and sleep.\u003c/p\u003e \u003cp\u003eInfancy, childhood history, and developmental milestones were unremarkable. There was no history of attentional difficulties, hyperactivity, impulsivity, or behavioural dysregulation in early or middle childhood, and no concerns suggestive of a primary neurodevelopmental disorder.\u003c/p\u003e \u003cp\u003eElmond was diagnosed with CLN3 at age 8 via genetic testing, following the diagnosis of the same neurodegenerative disorder as his sister after she developed symptoms. From 10 age 10, he developed progressive visual impairment affecting night vision, depth perception, and peripheral vision. By age 12, this limited participation in sports. He also developed learning difficulties, requiring classroom aide supports and visual assistance within a mainstream school setting, including the use of a computer for all reading.\u003c/p\u003e \u003cp\u003eFrom late childhood, he experienced sleep onset difficulties that improved with melatonin, as well as intermittent behavioural outbursts characterised by irritability and emotional lability. Anxiety symptoms emerged around age 12 and were managed with community-based psychological therapy.\u003c/p\u003e \u003cp\u003eFrom age 12, he developed intermittent involuntary movements including head shaking, shoulder shrugging, and complex motor behaviours. Video EEG recordings demonstrated no epileptiform activity, and these events were characterised as complex motor tics. Neuroimaging identified a mild Chiari I malformation, yet remained seizure-free.\u003c/p\u003e \u003cp\u003eBetween ages 13 and 15, there was a progressive deterioration in attention, working memory, dysregulation, and increasing fatigue. During this period, behavioural outbursts escalated in frequency and intensity, at times involving physical aggression toward family members, followed by remorse or denial. School participation became increasingly challenging with reported memory and attentional difficulties and difficulties retaining learned material. The symptoms worsened throughout the day due to progressive fatigue, typically peaking once the school day ended\u003c/p\u003e \u003cp\u003eNeuropsychological assessment at age 13 demonstrated low-average intellectual functioning with academic skills below grade level. Repeat assessment at age 15 demonstrated a stable overall cognitive profile with impairment in working memory, attention, and executive functioning. Standardised questionnaires completed by parents and teachers indicated clinically significant symptoms of ADHD across home and school settings.\u003c/p\u003e \u003cp\u003eAt age 15, he was referred to consultation-liaison psychiatry. Psychiatric assessment identified symptoms of inattention, impulsivity, and emotional dysregulation across multiple settings. There was no evidence of childhood-onset ADHD or family history of the disorder. His presentation was conceptualised as ADHD secondary to the CLN3, with contributory factors including disease-associated fatigue and insomnia, emotional adjustment to chronic illness, and carer burden for 2 children with neurodegenerative disease.\u003c/p\u003e \u003cp\u003eAfter limited effectiveness of psychological interventions for emotional dysregulation, a trial of methylphenidate was commenced at age 15 years and 6 months. Both Elmond and his parents reported marked improvements in attention, emotional and behavioural regulation, mood stability, family functioning, and school engagement. He reported improved concentration and reduced irritability. The medication was well tolerated, with manageable appetite suppression and no clinically significant worsening of sleep or involuntary movements. With improvement in mood and attention, Elmond and his family were able to engage meaningfully in concurrent psychological interventions. These sessions addressed family relationship and adjusting to his degenerative disease, emphasising a values-driven approach to living. Liaison with Elmond’s school led to specific educational adjustments to support the secondary ADHD diagnosis.\u003c/p\u003e "},{"header":"Discussion and Conclusions","content":"\u003cp\u003eThis case report is the first to describe the conceptualisation and management of a specific cluster of behavioural difficulties in a patient with CLN3, as secondary ADHD. Behavioural and emotional disturbance is well documented in CLN3 and is recognised as a major contributor to reduced quality of life for patients and families (\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e). However, the literature typically describes these difficulties in non-specific terms such as irritability or behavioural problems. This case report highlights that such symptoms may cluster into a recognisable and clinically meaningful syndrome consistent with secondary ADHD.\u003c/p\u003e\u003cp\u003eIn this case, formal psychiatric assessment and neuropsychological testing demonstrated cross setting impairment, prominent executive dysfunction, and working memory limitations, supporting this formulation. Notably, the patient demonstrated a marked and sustained response to stimulant treatment with improvements in attention, behavioural regulation, emotional stability, school engagement, and family functioning. This raises the possibility that stimulant treatment may be effective in addressing similar behavioural phenotypes in CLN3, as has been shown in other neurological pathologies with secondary ADHD.\u003c/p\u003e\u003cp\u003eThis conceptual framework also supports the use of tailored non-pharmacological interventions which are commonly used to support children with ADHD, including school liaison, behavioural supports, and educational accommodations. The introduction of stimulant medication supported Elmond’s engagement in psychological therapy and his schooling. Beyond addressing frequent behavioural escalations, Elmond was able to engage meaningfully in dialogue about how he understands his CLN3 diagnosis, how it affects him, what he can control in his life and what he cannot, and how he can act in accordance with his values.\u003c/p\u003e\u003cp\u003eThis case highlights how recognising this phenotype may facilitate targeted pharmacological and non-pharmacological interventions, with the potential to significantly improve quality of life and outcomes for adolescents living with juvenile Batten disease. While the generalisability of a single case report is inherently constrained, this framework for CLN3 associated secondary ADHD, and the observed efficacy of stimulant therapy, provides impetus for further case series and research into the management of phenotypes in CLN3.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eADHD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAttention deficit hyperactivity disorder\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCLN3\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNeuronal ceroid lipofuscinosis type 3\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEEG\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eElectroencephalogram\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eEthics Approval and Consent to Participate\u003c/h2\u003e \u003cp\u003eEthics approval was obtained from the Sydney Children\u0026rsquo;s Hospital Network Human Research Ethics Committee. Written informed consent to participate was obtained from the patient\u0026rsquo;s parent.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication\u003c/strong\u003e \u003cp\u003eWritten informed consent for publication, including of clinical details, was obtained from the patient\u0026rsquo;s parent.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eCompeting interests\u003c/h2\u003e \u003cp\u003eNo potential conflict of interest is known by the authors.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eNo specific funding was received for this work.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eDY and MB reviewed the patient data and notes, clinical progress and management. DY prepared the initial manuscript draft. DY and MB contributed significant editing and review of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eMaterials are available from the corresponding author on request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eOstergaard JR. Juvenile neuronal ceroid lipofuscinosis (Batten disease): current insights. Degener Neurol Neuromuscul Dis. 2016;6:73\u0026ndash;83. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.2147/DNND.S111967\u003c/span\u003e\u003cspan address=\"10.2147/DNND.S111967\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAdams HR, Mink JW, University of Rochester Batten Center Study Group. Neurobehavioral features and natural history of juvenile neuronal ceroid lipofuscinosis (Batten disease). J Child Neurol. 2013;28(9):1128\u0026ndash;36. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1177/0883073813494813\u003c/span\u003e\u003cspan address=\"10.1177/0883073813494813\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHoningh AK, Kruithof YL, Kuper WF, van Hasselt PM, Sterkenburg PS. Towards understanding behaviour and emotions of children with CLN3 disease (Batten disease): patterns, problems and support for child and family. Int J Environ Res Public Health. 2022;19(10):5895. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/ijerph19105895\u003c/span\u003e\u003cspan address=\"10.3390/ijerph19105895\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKrantz M, Malm E, Darin N, Sofou K, Savvidou A, Reilly C, et al. Parental experiences of having a child with CLN3 disease (juvenile Batten disease) and how these experiences relate to family resilience. Child Care Health Dev. 2022;48(5):842\u0026ndash;51. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/cch.12993\u003c/span\u003e\u003cspan address=\"10.1111/cch.12993\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAsarnow RF, Newman N, Weiss RE, Su E. Association of attention-deficit/hyperactivity disorder diagnoses with pediatric traumatic brain injury: a meta-analysis. JAMA Pediatr. 2021;175(10):1009\u0026ndash;16. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1001/jamapediatrics.2021.2033\u003c/span\u003e\u003cspan address=\"10.1001/jamapediatrics.2021.2033\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStojanovski S, Scratch SE, Dunkley BT, Schachar R, Wheeler AL. A systematic scoping review of new attention problems following traumatic brain injury in children. Front Neurol. 2021;12:751736. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fneur.2021.751736\u003c/span\u003e\u003cspan address=\"10.3389/fneur.2021.751736\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePitt-Francis A, Stevens AR, Ahmed Z, Di Pietro V. The use of methylphenidate to improve executive functioning in pediatric traumatic brain injury: a systematic review and meta-analysis. Trauma Care. 2024;5(1):1. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/traumacare5010001\u003c/span\u003e\u003cspan address=\"10.3390/traumacare5010001\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Batten disease, CLN3, secondary ADHD, neurodegenerative disorders, stimulant treatment, adolescent psychiatry","lastPublishedDoi":"10.21203/rs.3.rs-8643968/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8643968/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eNeuronal ceroid lipofuscinosis type 3 (CLN3), also known as juvenile Batten disease, is a rare neurodegenerative disorder characterised by progressive visual loss, cognitive decline, and behavioural disturbance. Neuropsychiatric symptoms are common and are generally attributed to global neurodegeneration. Secondary attention-deficit/hyperactivity disorder (ADHD)—the emergence of ADHD symptoms following the onset of a neurological condition—has not previously been reported in CLN3. Nor has stimulant treatment of secondary ADHD in CLN3 been previously reported.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation\u003c/strong\u003e: We describe a 15-year-old boy with CLN3 who developed progressive inattention, impulsivity, emotional dysregulation, and behavioural aggression during early adolescence, in the absence of any childhood history consistent with primary ADHD. Neuropsychological assessment demonstrated evidence of reduced cognitive ability with disproportionate impairment in attention, working memory, and executive functioning. By age 13 his symptoms caused significant impairment across home and school settings. A diagnosis of secondary ADHD associated with CLN3 was made. Treatment with methylphenidate resulted in marked improvements in attention, aggression, school engagement, and had good tolerability.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eThis case highlights a previously unreported presentation of secondary ADHD in CLN3 and demonstrates that stimulant treatment may be effective in selected adolescents with this condition. Clinicians should be alert to the possibility of treatable secondary ADHD in CLN3.\u003c/p\u003e","manuscriptTitle":"Stimulant Treatment of Emergent ADHD Phenotype in Adolescent Batten Disease: A Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-23 09:06:27","doi":"10.21203/rs.3.rs-8643968/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-03-08T17:31:37+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-06T19:23:04+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"300557279952375269889871471617397936819","date":"2026-02-26T20:09:50+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"132871644918650250564547776734708763631","date":"2026-02-26T13:58:11+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-26T00:48:30+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-18T00:02:59+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"211250788885439396651745878581574097684","date":"2026-02-17T14:39:40+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"119897354143892819153245951210781635280","date":"2026-02-17T13:21:05+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-17T12:37:31+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-17T09:26:15+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-01-27T09:43:44+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-23T23:29:02+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pediatrics","date":"2026-01-23T23:24:51+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5939e6c3-262c-4fa1-9528-a0ece3cd5b8a","owner":[],"postedDate":"February 23rd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-02-23T09:06:27+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-23 09:06:27","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8643968","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8643968","identity":"rs-8643968","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}