Concussions and Idiopathic Normal Pressure Hydrocephalus: Is there a correlation?

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Mack Hancock, Gianluca Sorrento, David Tang-Wai, Charles H Tator, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3952254/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background. Normal Pressure Hydrocephalus (NPH) is an adult-onset communicating hydrocephalus characterized by an abnormal accumulation of cerebrospinal fluid. Idiopathic NPH (iNPH) is often underdiagnosed, and clear causes are not identified. Few studies have explored the potential link between iNPH and concussions despite that these entities share many pathophysiological traits. Methods. 56 consecutive iNPH patients were assessed by means of the Ohio State University TBI-ID and Brain Injury Screening Questionnaire designed by the Icahn School of Medicine and were compared to 40 patients with Parkinson’s disease (PD) and 40 healthy controls (HC). Results. 76.8% of iNPH patients reported at least one minor head trauma throughout their lifetime when compared to 47.5% and 25.0% of patients diagnosed with PD and HC, respectively. Conclusions. Our findings indicate a possible association between TBI/concussion and iNPH, an association that warrants further investigation. Normal pressure hydrocephalus concussion traumatic brain injury mild traumatic brain injury neurodegenerative disease Parkinson’s disease Figures Figure 1 Introduction Hydrocephalus involves abnormal cerebrospinal fluid (CSF) accumulation and presents in either non-communicating or communicating forms [ 1 ]. Normal pressure hydrocephalus (NPH) is an adult-onset type and features compromised reabsorption without CSF obstruction (i.e. communicating) that causes “Hakim’s triad” of gait/balance impairment, urinary frequency, and cognitive impairment [ 2 ]. Idiopathic NPH (iNPH) is often underdiagnosed due to the absence of clear causes or biomarkers [ 1 ]. Our study aims to explore the potential link between iNPH and concussion (also described as mild traumatic brain injury, mTBI) building on the established association between trauma and the risk of acquired NPH [ 1 , 3 ]. TBI affects millions of people and results from external forces impacting the head or body that causes a disruption in brain function [ 4 , 5 ]. Concussion and mTBI are the most common cause of TBI [ 4 ]. These terms, although indicating slightly different entities, are often used interchangeably in the literature. Concussion/mTBI are prevalent in contact sports, military personnel, motor vehicle accidents, and falls in older individuals [ 4 , 6 ]. The consequences of concussions are broad, encompassing symptoms like memory loss, headache, and neuropsychiatric symptoms. There is evidence that repeated concussions may increase the risk of post-traumatic brain degeneration, predisposing patients to neurodegenerative diseases like chronic traumatic encephalopathy (CTE), Alzheimer’s disease (AD) and Parkinson’s disease (PD) [ 6 , 8 ] which has also been found in iNPH patients [ 1 ]. This relationship emphasizes the need to explore the connection between concussion and iNPH, as they share key pathophysiological traits, including BBB disruption, white matter abnormalities, and ventricular dilation. Athletes in contact sports often show significant BBB disruption, through both concussive and sub-concussive impacts [ 5 , 6 ]. BBB dysfunction has also been linked to impaired neurovascular functioning in iNPH patients, similar to concussion patients [ 9 ]. White matter structure abnormalities are observed in both iNPH and CTE, with studies demonstrating altered tissue diffusivities post-concussions [ 9 , 10 ]. Finally, ventricular dilation is common to both CTE and iNPH [ 6 , 10 ]. Limited research has explored the link between lifetime concussions and iNPH, despite indications of elevated neurodegenerative disease risk associated with concussions [ 6 – 8 ], shared pathophysiological findings (e.g., intracranial pressure outcomes) [ 9 ] and the association between TBI and acquired NPH [ 3 ]. Thus, our study sought to explore the history of concussion in patients with iNPH diagnosis. Methods This study took place at the Movement Disorders Centre of Toronto Western Hospital with prior approval from the University Health Network research ethics committee (REB # 15-8777). A standardized case report form was developed using REDcap to collect demographic, lifestyle factors and clinical data regarding lifetime head injury exposure and other medical history. The study aimed to contact all iNPH patients followed by the clinic and a cohort of age- and sex-matched PD patients (263 individuals in total) from our database. Exclusion criteria included individuals who were unreachable, uninterested, had language barriers or were too ill to participate. The final sample included 56 iNPH patients and 40 PD patients (16 and 14 females, respectively). An additional 40 age- and sex-matched healthy controls (HC) cohort was selected from patients’ family members (20 females, p = 0.06). Mean age ± SD was 76.4 ± 6.6, 74.6 ± 9.1, and 73.1 ± 7.3 for iNPH, PD and HC, respectively ( p = 3.4). Disease duration was 7.65 ± 4.3 8.9 ± 5.3 years for iNPH and PD, respectively ( p = 0.82). Diagnoses were based on the latest criteria [ 11 , 12 ], while HC subjects were recruited from the family members of patients, contingent upon the absence of any noteworthy medical conditions in their medical history and normal neurological examination. Patients were interviewed via phone or in person, and their history of concussion was assessed using a case report form derived from the Ohio State University TBI-ID (OSU TBI-ID) and the Brain Injury Screening Questionnaire (BISQ). The lifetime occurrence of a head injury was considered up to 5 years before disease onset to exclude the possibility that fall-related traumas were early signs of PD or iNPH. OSU TBI-ID, a well-established tool in TBI research, employs a three-part structured interview to evaluate lifetime exposure to head trauma, demonstrating high reliability and validity [ 13 ]. BISQ, another widely recognized tool, screens for TBI, emphasizing detection when symptoms are less apparent, and exploring specific criteria and life areas where head trauma may occur [ 14 ]. By utilizing both methods, we leverage the strengths of OSU TBI-ID for assessing loss of consciousness (LOC) and typical TBI effects, and BISQ for analyzing TBI causes and lifetime experiences. Statistical Analysis Categorical head injury data for iNPH, PD, and HC groups were analyzed with the Pearson Chi-square tests and pairwise comparisons for significant relationships. Continuous variables (age, disease duration, number of head injury events, age at head injury, LOC duration, and time lag from trauma to iNPH or PD diagnosis) were collected and data was analyzed using an independent sample t-test or a one-way ANOVA. Additional categorical variables (sex, the occurrence of LOC, concussion mechanisms – falls, vehicle accidents, sports, unknown – hospitalizations due to concussion) were also analyzed with the Pearson Chi-square test and subsequent Bonferroni correction and pairwise comparison for significant relationships. Results The NPH group showed a significantly greater proportion (n = 43, 76.8%) with a history of head injury, compared to the PD (n = 19, 47.5%) and HC (n = 10, 25.0%) groups ( X 2 = 23.66, df = 2 p = .00000726; Fig. 1). The HC group reported the highest proportion of LOC events (n = 5, 50.0%), the NPH group the second highest proportion (n = 12, 27.9%) and the PD group had the lowest proportion (n = 3, 15.8%) (Fig. 1). The HC group reported the highest proportion of hospitalizations due to head injury (n = 9, 90.0%) while the NPH (n = 22, 51.16%) and PD (n = 11, 57.9%) groups both showed a similar proportion (Fig. 1). Nevertheless, no significant statistical between-groups difference was detected ( X 2 = 3.4048, df = 2, p = .182248 and X 2 = 2.767, df = 2, p = .250696, respectively). Head injury mechanisms were examined for all patients, revealing variations among the iNPH, PD, and HC groups (Table 1 ). In the iNPH group, falling while walking constituted the predominant head injury mechanism (25.6%, not different from other groups), while the PD group showed higher proportions for falling while walking (26.3%, not different from other groups) and sports injuries (26.3%, significantly different than HC, p = .00096). In contrast, the HC group predominantly experienced head injuries from vehicle and bike accidents (30.0%, significantly higher than iNPH and PD). Statistically significant differences were observed across the three groups for vehicle accidents, bike accidents, sports injuries, falls from high places, head injury by an object, neck injury, physical abuse, and being hit by a car as a pedestrian (Table 1 ). Table 1 Mechanism of injury for subjects with head Injury. iNPH (n: 43) PD (n: 19) HC (n: 10) P-value iNPH vs PD iNPH vs HC PD vs HC Vehicle Accident 18.6% 15.8% 40% < 0.0001 0.0135 0.0018 0.5272 Bike Accident 11.60% 10.50% 30% < 0.0001 0.5253 < 0.001 < 0.001 Sports Injury 18.60% 26.30% 0 < 0.0001 0.0016 < 0.0001 < 0.001 Fall from high place 6.90% 5.30% 0 0.013 0.0212 0.8929 0.0172 Fall walking 25.60% 26.30% 20% 0.46 - - - Hit by object 11.60% 0 10% 0.0005 0.00214 0.6201 0.000723 Fall during fainting spell 11.60% 0 0 1.726 - - - Neck Injury 0 5.30% 0 0.002 0.005 - - Physical Abuse 0 5.30% 0 0.002 0.005 - - Hit by Car as Pedestrian 4.70% 5.30% 0 0.045 0.4425 0.0603 0.0172 Abbreviations: HC: Healthy Control subject; iNPH: idiopathic Normal Pressure Hydrocephalus subject; PD: Parkinson’s Disease subject. Discussion To our knowledge, this is the first study to examine the relationship between concussion and iNPH. Among the 56 iNPH patients, 40 PD controls, and 40 healthy controls sampled, we found evidence that prior head trauma is commonly reported in patients with an established diagnosis of iNPH. These findings are plausible given the shared aspects of iNPH and concussion pathogenesis outlined in the introduction. Key pathophysiological similarities include reduced cerebral blood flow in both NPH [14] and TBI [5] patients. Additionally, both conditions exhibit alterations in white matter structure. In NPH, gait abnormalities are linked to microstructural damage in motor and sensory pathways around the ventricles [10], while TBI is associated with abnormalities in white matter tracts as well as generalized cerebral atrophy [6, 15]. This study is not without limitations. Challenges include recall bias, evolving diagnoses, cognitive impairments, and timing of symptoms as several patients suffered from mild gait and imbalance changes that were not sufficient to seek medical attention. Limitations in diagnosing concussions as the mechanism of injury should be noted. Although patients with iNPH or PD reported concussions, no association with intracranial processes was observed in these groups. Additionally, determining the interval between concussion and the earliest gait complaint was challenging due to recall limitations and the lack of definitive diagnoses during those periods. The study prompts further investigation into imaging similarities for predictive concussion features aiding iNPH detection, with larger studies on genetic and environmental factors warranted. Acknowledging data collection challenges, especially recall bias, is crucial given the unique focus on the iNPH-concussion relationship. Selecting suitable healthy controls, mainly spouses of iNPH patients has limitations due to shared injury mechanisms. Some groups had a smaller number of cases, impacting statistical inferences. The lack of proven biomarkers for concussion diagnosis adds complexity, but to mitigate these shortcomings, we opted for two widely adopted and validated scales. In conclusion, our study suggests a potential association between iNPH and a history of concussion. Future research should expand the sample sizes and explore additional research protocols, e.g. studying national registries. Consideration should be given to the evolving landscape of concussion research, particularly as most reported concussions in our study occurred before recent advancements in this field. Declarations ACKNOWLEDGEMENT Study was partly funded by the University of Toronto and University Health Network Chair in Neuromodulation (AF). AUTHORS’ ROLES Research project: A. Conception, B. Organization, C. Execution. Statistical Analysis: A. Design, B. Execution, C. Review and Critique. Manuscript Preparation: A. Writing of the first draft, B. Review and Critique. MH: 1C, 2A, 2B, 3A GUS: 2B, 2C, 3B DTW: 2C, 3B CHT: 2C, 3B CT: 2C, 3B AF: 1A, 1B, 2C, 3B FUNDING SOURCES AND CONFLICT OF INTEREST AF received honoraria from Integra and Medtronic, manufacturers of ventricular-peritoneal shunts. FINANCIAL DISCLOSURES FOR THE PREVIOUS 12 MONTHS MH , GS, CHT and CT have no disclosures to report. DTW is on the medical advisory board for Hydrocephalus Canada – no financial compensation. AF is on the medical advisory board for Hydrocephalus Canada – no financial compensation; he has received grant support from Abbvie, Boston Scientific, Dystonia Medical Research Foundation, University of Toronto, Michael J Fox Foundation, Medtronic, MSA coalition; personal compensation as a consultant/scientific advisory board member for Abbvie, Abbott, Boston Scientific, Ceregate, Inbrain, Ipsen, Medtronic, Sunovion; publishing royalties from Springer; and honoraria from Abbvie, Abbott, American Academy of Neurology, Boston Scientific, Brainlab, Ipsen, Medtronic, Merz, Movement Disorders Society, Sunovion, Paladin Labs, UCB pharma. ETHICAL COMPLIANCE STATEMENT All study procedures were performed in accordance with the ethical standards of the 1964 Declaration of Helsinki and its later amendments. The authors confirm that they have read the Journal’s position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. DATA SHARING MH and AF had full access to all the data in the study and took responsibility for the integrity of the data, the accuracy of the data analysis, and the conduct of the research. They have the right to publish any and all data, separate and apart from the guidance of any sponsor. References Fasano A, Espay AJ, Tang-Wai DF, Wikkelsö C, et al. Gaps, Controversies, and Proposed Roadmap for Research in Normal Pressure Hydrocephalus. Mov Disord. 2020;35(11):1945–54. 10.1002/mds.28251 . Bluett B, Ash E, Farheen A, et al. Clinical Features of Idiopathic Normal Pressure Hydrocephalus: Critical Review of Objective Findings. Mov Disord Clin Pract. 2023;10(1):9–16. 10.1002/mdc3.13608 . Daou B, Klinge P, Tjoumakaris S, Rosenwasser RH, Jabbour P. Revisiting secondary normal pressure hydrocephalus: does it exist? A review. FOC. 2016;41(3):E6. 10.3171/2016.6.FOCUS16189 . Tator CH. Concussions and their consequences: current diagnosis, management and prevention. CMAJ. 2013;185(11):975–9. 10.1503/cmaj.120039 . Ng SY, Lee AYW. Traumatic Brain Injuries: Pathophysiology and Potential Therapeutic Targets. Front Cell Neurosci. 2019;13:528. 10.3389/fncel.2019.00528 . McKee AC, Cantu RC, Nowinski CJ, et al. Chronic Traumatic Encephalopathy in Athletes: Progressive Tauopathy After Repetitive Head Injury. J Neuropathol Exp Neurol. 2009;68(7):709–35. 10.1097/NEN.0b013e3181a9d503 . Gardner RC, Yaffe K. Epidemiology of mild traumatic brain injury and neurodegenerative disease. Mol Cell Neurosci. 2015;66:75–80. 10.1016/j.mcn.2015.03.001 . Fang F, Chen H, Feldman AL, et al. Head injury and Parkinson’s disease: A population-based study. Mov Disord. 2012;27(13):1632–5. 10.1002/mds.25143 . Eide PK, Hansson HA. Blood-brain barrier leakage of blood proteins in idiopathic normal pressure hydrocephalus. Brain Res. 2020;1727:146547. 10.1016/j.brainres.2019.146547 . Tang Ymin, Yao Y, Xu S, et al. White Matter Microstructural Damage Associated with Gait Abnormalities in Idiopathic Normal Pressure Hydrocephalus. Front Aging Neurosci. 2021;13. 10.3389/fnagi.2021.660621 . Nakajima M, Yamada S, Miyajima M, et al. Guidelines for Management of Idiopathic Normal Pressure Hydrocephalus (Third Edition): Endorsed by the Japanese Society of Normal Pressure Hydrocephalus. Neurol Med Chir(Tokyo). 2021;61(2):63–97. 10.2176/nmc.st.2020-0292 . Postuma RB, Berg D, Stern M, et al. MDS clinical diagnostic criteria for Parkinson’s disease: MDS-PD Clinical Diagnostic Criteria. Mov Disord. 2015;30(12):1591–601. 10.1002/mds.26424 . Corrigan JD, Bogner J. Initial Reliability and Validity of the Ohio State University TBI Identification Method. J Head Trauma Rehabil. 2007;22(6):318–29. doi: 0.1097/01.HTR.0000300227.67748.77. Das M, Biagioni J. Normal Pressure Hydrocephalus. StatPearls. Treasure Island (FL). PMID: StatPearls Publishing; 2023. p. 31194404. Misquitta K, Dadar M, Tarazi A, et al. The relationship between brain atrophy and cognitive-behavioural symptoms in retired Canadian football players with multiple concussions. Neuroimage Clin. 2018;19:551–8. 10.1016/j.nicl.2018.05.014 . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-3952254","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":272780200,"identity":"c80b53c9-6603-41f0-9092-f00ba3e0efe0","order_by":0,"name":"Mack Hancock","email":"","orcid":"","institution":"Dalhousie University","correspondingAuthor":false,"prefix":"","firstName":"Mack","middleName":"","lastName":"Hancock","suffix":""},{"id":272780201,"identity":"4c91cbad-831b-449b-9478-d3d6635528a6","order_by":1,"name":"Gianluca Sorrento","email":"","orcid":"","institution":"Toronto Western Hospital, UHN","correspondingAuthor":false,"prefix":"","firstName":"Gianluca","middleName":"","lastName":"Sorrento","suffix":""},{"id":272780202,"identity":"881593ae-84db-465c-bc9e-8612acf8a8d9","order_by":2,"name":"David Tang-Wai","email":"","orcid":"","institution":"University of Toronto","correspondingAuthor":false,"prefix":"","firstName":"David","middleName":"","lastName":"Tang-Wai","suffix":""},{"id":272780203,"identity":"920ad4b2-fd3c-4bc2-a22a-731adc6bad41","order_by":3,"name":"Charles H Tator","email":"","orcid":"","institution":"Krembil Brain Institute","correspondingAuthor":false,"prefix":"","firstName":"Charles","middleName":"H","lastName":"Tator","suffix":""},{"id":272780204,"identity":"9fbbae30-1db1-42c0-978f-616a0c5eae06","order_by":4,"name":"Carmela Tartaglia","email":"","orcid":"","institution":"University of Toronto","correspondingAuthor":false,"prefix":"","firstName":"Carmela","middleName":"","lastName":"Tartaglia","suffix":""},{"id":272780205,"identity":"e213aa03-a990-492d-b67c-3e5b84553f1e","order_by":5,"name":"Alfonso Fasano","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7ElEQVRIiWNgGAWjYDACdsYHELoBTNkwGBDUwswMUcNzAEylka7lMGEt/M3MjI8L/tgw8LAff/i5oOJ84nbpBsYPP/BokTjMzGw8sy2NgYcnx1h6xpnbiTvnHGCW7MFnzWH+Y9K8DYcZ7BlyGKR5224nbriRwMbAg0eH/GFmNmmeP4cZePifP/7N23YOrIXxDx4tBmAtbEAtEglmQFsOgLUw47PFEOQX3rY0Hh6JN2bWPGeSjTfcSGyWlsGjRe54M+Njnj82cjz86Y9v81TYyW64kXzw4xt83ocCZJcwNhChYRSMglEwCkYBPgAA63hFXCBrF3EAAAAASUVORK5CYII=","orcid":"","institution":"Toronto Western Hospital, UHN","correspondingAuthor":true,"prefix":"","firstName":"Alfonso","middleName":"","lastName":"Fasano","suffix":""}],"badges":[],"createdAt":"2024-02-13 00:19:48","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3952254/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3952254/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":51189924,"identity":"ef384178-a6ee-4599-8130-1d29acfe10e0","added_by":"auto","created_at":"2024-02-15 16:52:29","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":50298,"visible":true,"origin":"","legend":"\u003cp\u003eTotal cases reviewed and confirmed for concussions, loss of consciousness, and hospitalizations for all groups.\u003c/p\u003e\n\u003cp\u003eAbbreviations: HC: Healthy Control subject; iNPH: idiopathic Normal Pressure Hydrocephalus; PD: Parkinson’s Disease.\u003c/p\u003e","description":"","filename":"Picture1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3952254/v1/df0cb60869aeda60afdd327c.jpg"},{"id":53609998,"identity":"2a75a531-0b89-447c-9d75-ec634459b1c1","added_by":"auto","created_at":"2024-03-28 04:56:16","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":280800,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3952254/v1/bf7fc5a6-58a5-4a19-a4f9-b2890d03d3cb.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Concussions and Idiopathic Normal Pressure Hydrocephalus: Is there a correlation?","fulltext":[{"header":"Introduction","content":"\u003cp\u003eHydrocephalus involves abnormal cerebrospinal fluid (CSF) accumulation and presents in either non-communicating or communicating forms [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Normal pressure hydrocephalus (NPH) is an adult-onset type and features compromised reabsorption without CSF obstruction (i.e. communicating) that causes \u0026ldquo;Hakim\u0026rsquo;s triad\u0026rdquo; of gait/balance impairment, urinary frequency, and cognitive impairment [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Idiopathic NPH (iNPH) is often underdiagnosed due to the absence of clear causes or biomarkers [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Our study aims to explore the potential link between iNPH and concussion (also described as mild traumatic brain injury, mTBI) building on the established association between trauma and the risk of acquired NPH [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTBI affects millions of people and results from external forces impacting the head or body that causes a disruption in brain function [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Concussion and mTBI are the most common cause of TBI [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. These terms, although indicating slightly different entities, are often used interchangeably in the literature. Concussion/mTBI are prevalent in contact sports, military personnel, motor vehicle accidents, and falls in older individuals [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. The consequences of concussions are broad, encompassing symptoms like memory loss, headache, and neuropsychiatric symptoms. There is evidence that repeated concussions may increase the risk of post-traumatic brain degeneration, predisposing patients to neurodegenerative diseases like chronic traumatic encephalopathy (CTE), Alzheimer\u0026rsquo;s disease (AD) and Parkinson\u0026rsquo;s disease (PD) [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] which has also been found in iNPH patients [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. This relationship emphasizes the need to explore the connection between concussion and iNPH, as they share key pathophysiological traits, including BBB disruption, white matter abnormalities, and ventricular dilation. Athletes in contact sports often show significant BBB disruption, through both concussive and sub-concussive impacts [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. BBB dysfunction has also been linked to impaired neurovascular functioning in iNPH patients, similar to concussion patients [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. White matter structure abnormalities are observed in both iNPH and CTE, with studies demonstrating altered tissue diffusivities post-concussions [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Finally, ventricular dilation is common to both CTE and iNPH [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eLimited research has explored the link between lifetime concussions and iNPH, despite indications of elevated neurodegenerative disease risk associated with concussions [\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], shared pathophysiological findings (e.g., intracranial pressure outcomes) [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] and the association between TBI and acquired NPH [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Thus, our study sought to explore the history of concussion in patients with iNPH diagnosis.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e This study took place at the Movement Disorders Centre of Toronto Western Hospital with prior approval from the University Health Network research ethics committee (REB # 15-8777).\u003c/p\u003e \u003cp\u003eA standardized case report form was developed using REDcap to collect demographic, lifestyle factors and clinical data regarding lifetime head injury exposure and other medical history. The study aimed to contact all iNPH patients followed by the clinic and a cohort of age- and sex-matched PD patients (263 individuals in total) from our database. Exclusion criteria included individuals who were unreachable, uninterested, had language barriers or were too ill to participate. The final sample included 56 iNPH patients and 40 PD patients (16 and 14 females, respectively). An additional 40 age- and sex-matched healthy controls (HC) cohort was selected from patients\u0026rsquo; family members (20 females, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.06). Mean age\u0026thinsp;\u0026plusmn;\u0026thinsp;SD was 76.4\u0026thinsp;\u0026plusmn;\u0026thinsp;6.6, 74.6\u0026thinsp;\u0026plusmn;\u0026thinsp;9.1, and 73.1\u0026thinsp;\u0026plusmn;\u0026thinsp;7.3 for iNPH, PD and HC, respectively (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;3.4). Disease duration was 7.65\u0026thinsp;\u0026plusmn;\u0026thinsp;4.3 8.9\u0026thinsp;\u0026plusmn;\u0026thinsp;5.3 years for iNPH and PD, respectively (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.82).\u003c/p\u003e \u003cp\u003eDiagnoses were based on the latest criteria [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], while HC subjects were recruited from the family members of patients, contingent upon the absence of any noteworthy medical conditions in their medical history and normal neurological examination.\u003c/p\u003e \u003cp\u003ePatients were interviewed via phone or in person, and their history of concussion was assessed using a case report form derived from the Ohio State University TBI-ID (OSU TBI-ID) and the Brain Injury Screening Questionnaire (BISQ). The lifetime occurrence of a head injury was considered up to 5 years before disease onset to exclude the possibility that fall-related traumas were early signs of PD or iNPH. OSU TBI-ID, a well-established tool in TBI research, employs a three-part structured interview to evaluate lifetime exposure to head trauma, demonstrating high reliability and validity [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. BISQ, another widely recognized tool, screens for TBI, emphasizing detection when symptoms are less apparent, and exploring specific criteria and life areas where head trauma may occur [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. By utilizing both methods, we leverage the strengths of OSU TBI-ID for assessing loss of consciousness (LOC) and typical TBI effects, and BISQ for analyzing TBI causes and lifetime experiences.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eCategorical head injury data for iNPH, PD, and HC groups were analyzed with the Pearson Chi-square tests and pairwise comparisons for significant relationships. Continuous variables (age, disease duration, number of head injury events, age at head injury, LOC duration, and time lag from trauma to iNPH or PD diagnosis) were collected and data was analyzed using an independent sample t-test or a one-way ANOVA. Additional categorical variables (sex, the occurrence of LOC, concussion mechanisms \u0026ndash; falls, vehicle accidents, sports, unknown \u0026ndash; hospitalizations due to concussion) were also analyzed with the Pearson Chi-square test and subsequent Bonferroni correction and pairwise comparison for significant relationships.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThe NPH group showed a significantly greater proportion (n\u0026thinsp;=\u0026thinsp;43, 76.8%) with a history of head injury, compared to the PD (n\u0026thinsp;=\u0026thinsp;19, 47.5%) and HC (n\u0026thinsp;=\u0026thinsp;10, 25.0%) groups (\u003cem\u003eX\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;23.66, df\u0026thinsp;=\u0026thinsp;2 \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.00000726; Fig.\u0026nbsp;1).\u003c/p\u003e \u003cp\u003eThe HC group reported the highest proportion of LOC events (n\u0026thinsp;=\u0026thinsp;5, 50.0%), the NPH group the second highest proportion (n\u0026thinsp;=\u0026thinsp;12, 27.9%) and the PD group had the lowest proportion (n\u0026thinsp;=\u0026thinsp;3, 15.8%) (Fig.\u0026nbsp;1). The HC group reported the highest proportion of hospitalizations due to head injury (n\u0026thinsp;=\u0026thinsp;9, 90.0%) while the NPH (n\u0026thinsp;=\u0026thinsp;22, 51.16%) and PD (n\u0026thinsp;=\u0026thinsp;11, 57.9%) groups both showed a similar proportion (Fig.\u0026nbsp;1). Nevertheless, no significant statistical between-groups difference was detected (\u003cem\u003eX\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;3.4048, df\u0026thinsp;=\u0026thinsp;2, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.182248 and \u003cem\u003eX\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;2.767, df\u0026thinsp;=\u0026thinsp;2, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.250696, respectively).\u003c/p\u003e \u003cp\u003eHead injury mechanisms were examined for all patients, revealing variations among the iNPH, PD, and HC groups (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). In the iNPH group, falling while walking constituted the predominant head injury mechanism (25.6%, not different from other groups), while the PD group showed higher proportions for falling while walking (26.3%, not different from other groups) and sports injuries (26.3%, significantly different than HC, p\u0026thinsp;=\u0026thinsp;.00096). In contrast, the HC group predominantly experienced head injuries from vehicle and bike accidents (30.0%, significantly higher than iNPH and PD). Statistically significant differences were observed across the three groups for vehicle accidents, bike accidents, sports injuries, falls from high places, head injury by an object, neck injury, physical abuse, and being hit by a car as a pedestrian (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMechanism of injury for subjects with head Injury.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eiNPH\u003c/p\u003e \u003cp\u003e(n: 43)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePD\u003c/p\u003e \u003cp\u003e(n: 19)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHC\u003c/p\u003e \u003cp\u003e(n: 10)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eiNPH vs PD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eiNPH vs HC\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003ePD vs HC\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eVehicle Accident\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18.6%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15.8%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.0135\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.5272\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBike Accident\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.60%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.50%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.5253\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSports Injury\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18.60%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26.30%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.0016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFall from high place\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.90%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.30%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.0212\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.8929\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.0172\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFall walking\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.60%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26.30%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHit by object\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.60%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.0005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.00214\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.6201\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.000723\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFall during fainting spell\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.60%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.726\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNeck Injury\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.30%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePhysical Abuse\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.30%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHit by Car as Pedestrian\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.70%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.30%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.045\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.4425\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0603\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.0172\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eAbbreviations: HC: Healthy Control subject; iNPH: idiopathic Normal Pressure Hydrocephalus subject; PD: Parkinson\u0026rsquo;s Disease subject.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e "},{"header":"Discussion","content":"\u003cp\u003eTo our knowledge, this is the first study to examine the relationship between concussion and iNPH. Among the 56 iNPH patients, 40 PD controls, and 40 healthy controls sampled, we found evidence that prior head trauma is commonly reported in patients with an established diagnosis of iNPH.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThese findings are plausible given the shared aspects of iNPH and\u0026nbsp;concussion\u0026nbsp;pathogenesis outlined in the introduction. Key pathophysiological similarities include reduced cerebral blood flow in both NPH [14] and TBI [5] patients. Additionally, both conditions exhibit alterations in white matter structure. In NPH, gait abnormalities are linked to microstructural damage in motor and sensory pathways around the ventricles [10], while TBI is associated with abnormalities in white matter tracts\u0026nbsp;as well as generalized cerebral atrophy\u0026nbsp;[6, 15].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis study is not without limitations. Challenges include recall bias, evolving diagnoses,\u0026nbsp;\u0026nbsp; \u0026nbsp; \u0026nbsp;cognitive\u0026nbsp;impairments, and timing of symptoms as several patients suffered from mild gait and imbalance changes that were not sufficient to seek medical attention. Limitations in diagnosing concussions as the mechanism of injury should be noted. Although patients with iNPH or PD reported concussions, no association with intracranial processes was observed in these groups. Additionally, determining the interval between concussion and the earliest gait complaint was challenging due to recall limitations and the lack of definitive diagnoses during those periods.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe study prompts further investigation into imaging similarities for predictive concussion features aiding iNPH detection, with larger studies on genetic and environmental factors warranted. Acknowledging data collection challenges, especially recall bias, is crucial given the unique focus on the iNPH-concussion relationship. Selecting suitable healthy controls, mainly spouses of iNPH patients has limitations due to shared injury mechanisms. Some groups had a smaller number of cases, impacting statistical inferences. The lack of proven biomarkers for concussion diagnosis adds complexity, but to mitigate these shortcomings, we opted for two widely adopted and validated scales.\u003c/p\u003e\n\u003cp\u003eIn conclusion, our study suggests a potential association between iNPH and a history of concussion. Future research should expand the sample sizes and explore additional research protocols, e.g. studying national registries. Consideration should be given to the evolving landscape of concussion research, particularly as most reported concussions in our study occurred before recent advancements in this field.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eACKNOWLEDGEMENT\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStudy was partly funded by the\u0026nbsp;University of Toronto and University Health Network Chair in Neuromodulation (AF).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAUTHORS\u0026rsquo; ROLES\u003c/strong\u003e\u003c/p\u003e\n\u003col start=\"1\" type=\"1\"\u003e\n \u003cli\u003eResearch project: A. Conception, B. Organization, C. Execution.\u003c/li\u003e\n \u003cli\u003eStatistical Analysis: A. Design, B. Execution, C. Review and Critique.\u003c/li\u003e\n \u003cli\u003eManuscript Preparation: A. Writing of the first draft, B. Review and Critique.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eMH: 1C, 2A, 2B, 3A\u003c/p\u003e\n\u003cp\u003eGUS: 2B, 2C, 3B\u003c/p\u003e\n\u003cp\u003eDTW: 2C, 3B\u003c/p\u003e\n\u003cp\u003eCHT: 2C, 3B\u003c/p\u003e\n\u003cp\u003eCT: 2C, 3B\u003c/p\u003e\n\u003cp\u003eAF: 1A, 1B, 2C, 3B\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFUNDING SOURCES AND CONFLICT OF INTEREST\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAF received honoraria from Integra and Medtronic, manufacturers of ventricular-peritoneal shunts.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFINANCIAL DISCLOSURES FOR THE PREVIOUS 12 MONTHS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMH\u003c/strong\u003e,\u0026nbsp;\u003cstrong\u003eGS, CHT and CT\u0026nbsp;\u003c/strong\u003ehave no disclosures to report.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDTW\u003c/strong\u003e is on the medical advisory board for Hydrocephalus Canada \u0026ndash; no financial compensation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAF\u0026nbsp;\u003c/strong\u003eis on the\u0026nbsp;medical advisory board for Hydrocephalus Canada \u0026ndash; no financial compensation; he\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ehas received grant support from Abbvie, Boston Scientific, Dystonia Medical Research Foundation, University of Toronto, Michael J Fox Foundation, Medtronic, MSA coalition; personal compensation as a consultant/scientific advisory board member for Abbvie, Abbott, Boston Scientific, Ceregate, Inbrain, Ipsen, Medtronic, Sunovion; publishing royalties from Springer; and honoraria from Abbvie, Abbott, American Academy of Neurology, Boston Scientific, Brainlab, Ipsen, Medtronic, Merz, Movement Disorders Society, Sunovion, Paladin Labs, UCB pharma.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eETHICAL COMPLIANCE STATEMENT\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll study procedures were performed in accordance with the ethical standards of the 1964 Declaration of Helsinki and its later amendments. The authors confirm that they have read the Journal\u0026rsquo;s position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDATA SHARING\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMH and AF had full access to all the data in the study and took responsibility for the integrity of the data, the accuracy of the data analysis, and the conduct of the research. They have the right to publish any and all data, separate and apart from the guidance of any sponsor.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eFasano A, Espay AJ, Tang-Wai DF, Wikkels\u0026ouml; C, et al. Gaps, Controversies, and Proposed Roadmap for Research in Normal Pressure Hydrocephalus. 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Neuroimage Clin. 2018;19:551\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.nicl.2018.05.014\u003c/span\u003e\u003cspan address=\"10.1016/j.nicl.2018.05.014\" 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":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Normal pressure hydrocephalus, concussion, traumatic brain injury, mild traumatic brain injury, neurodegenerative disease, Parkinson’s disease","lastPublishedDoi":"10.21203/rs.3.rs-3952254/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3952254/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground.\u003c/h2\u003e \u003cp\u003eNormal Pressure Hydrocephalus (NPH) is an adult-onset communicating hydrocephalus characterized by an abnormal accumulation of cerebrospinal fluid. Idiopathic NPH (iNPH) is often underdiagnosed, and clear causes are not identified. Few studies have explored the potential link between iNPH and concussions despite that these entities share many pathophysiological traits.\u003c/p\u003e\u003ch2\u003eMethods.\u003c/h2\u003e \u003cp\u003e56 consecutive iNPH patients were assessed by means of the Ohio State University TBI-ID and Brain Injury Screening Questionnaire designed by the Icahn School of Medicine and were compared to 40 patients with Parkinson\u0026rsquo;s disease (PD) and 40 healthy controls (HC).\u003c/p\u003e\u003ch2\u003eResults.\u003c/h2\u003e \u003cp\u003e76.8% of iNPH patients reported at least one minor head trauma throughout their lifetime when compared to 47.5% and 25.0% of patients diagnosed with PD and HC, respectively.\u003c/p\u003e\u003ch2\u003eConclusions.\u003c/h2\u003e \u003cp\u003eOur findings indicate a possible association between TBI/concussion and iNPH, an association that warrants further investigation.\u003c/p\u003e","manuscriptTitle":"Concussions and Idiopathic Normal Pressure Hydrocephalus: Is there a correlation?","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-02-15 16:52:24","doi":"10.21203/rs.3.rs-3952254/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d6046e97-3d18-46e8-a6b3-2c1325a00419","owner":[],"postedDate":"February 15th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-04-27T19:39:53+00:00","versionOfRecord":[],"versionCreatedAt":"2024-02-15 16:52:24","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3952254","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3952254","identity":"rs-3952254","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}