Developing New Ways to Detect Respiratory Impairment Early in ALS
Early Detection of Respiratory Impairments in ALS: A Novel Diagnostic Approach
The goal of this observational study is to develop new ways to detect early changes associated with amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. The study will examine whether changes in breathing, magnetic resonance imaging (MRI) of the brainstem and spinal cord, and blood markers can identify early signs of ALS before major physical changes occur.
The main questions the study aims to answer are:
- Can changes in automatic breathing help identify early ALS-related changes?
- Can breathing measures distinguish people with ALS from people without ALS?
- Do people with genetic risk for ALS who show changes in breathing also have changes in the brainstem and spinal cord or higher levels of blood markers associated with nerve damage?
Participants will complete breathing and muscle function tests, an MRI scan of the brainstem and spinal cord, and blood testing. The study will include people with ALS, people with genetic risk for ALS who do not yet have symptoms, and healthy adults for comparison.
調査の概要
状態
研究の種類
入学 (推定)
連絡先と場所
研究連絡先
- 名前：Jayakrishnan Nair, PhD, PT
- 電話番号：352-871-5888
- メール：Jayakrishnan.Nair@jefferson.edu
研究連絡先のバックアップ
- 名前：Dana Johnson, DPT
- 電話番号：215-326-9153
- メール：dana.johnson@jefferson.edu
研究場所
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Pennsylvania
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Philadelphia、Pennsylvania、アメリカ、19107
- 募集
- Thomas Jefferson University - Center City
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コンタクト：
- Jayakrishnan Nair, PhD, PT
- 電話番号：352-871-5888
- メール：Jayakrishnan.Nair@jefferson.edu
-
コンタクト：
- Dana Johnson, DPT
- 電話番号：215-326-9153
- メール：Dana.Johnson@jefferson.edu
-
主任研究者：
- Jayakrishnan Nair, PhD, PT
-
-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
サンプリング方法
調査対象母集団
The study population will include adults with symptomatic ALS, asymptomatic or presymptomatic individuals with genetic variants associated with ALS, and healthy age- and sex-matched controls. Participants with ALS or genetic risk for ALS will be recruited from Thomas Jefferson University and other ALS patient inventories and referral sources.
説明
Inclusion Criteria:
- Symptomatic participants with ALS must have an ALS Functional Rating Scale-Revised (ALSFRS-R) score of 47/48 or less at the time of recruitment.
- Asymptomatic/presymptomatic participants must have a pathogenic C9orf72 expansion of at least 25 repeats or a similar genetic abnormality known to be associated with ALS.
- Healthy control participants must have no clinically identifiable neurological deficits based on medical history and screening. -
Exclusion Criteria:
- Any safety concern or contraindication to MRI based on MRI safety screening.
- Healthy control participants who do not pass the neurological screening.
- Pregnancy.
- Metal implants above the waist, including cardiac pacemakers or brain, neck, cervical, or thoracic implants.
- Neurocognitive impairment.
- Inability or unwillingness to provide informed consent.
- Younger than 18 years of age.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 観測モデル：COHORT
- 時間の展望：PROSPECTIVE
コホートと介入
グループ/コホート |
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Symptomatic Amyotrophic Lateral Sclerosis
Participants with symptomatic amyotrophic lateral sclerosis (ALS), including familial or sporadic ALS, who have clinical evidence of disease. This group will undergo study assessments to characterize respiratory function and biomarkers associated with ALS. |
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Asymptomatic/Presymptomatic ALS Gene Carriers
Participants who carry a genetic variant associated with amyotrophic lateral sclerosis but do not have clinical symptoms or functional deficits associated with ALS. This group will be evaluated for early or subclinical changes in respiratory function and other biomarkers associated with ALS. |
|
Healthy Controls
Neurologically healthy participants without clinically identifiable neurological deficits who will serve as a comparison group for the study assessments. |
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Diagnostic Accuracy of the Automatic Breathing Impairment Risk Score (P0.1 + Chemosensitivity) for Detecting ALS-Related Respiratory Dysfunction
時間枠：During the single study visit
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A linear prediction risk score combining airway occlusion pressure at 0.1 seconds (P0.1) and chemosensitivity will be developed to distinguish symptomatic ALS participants with respiratory dysfunction from healthy controls. Diagnostic performance of the risk score will be evaluated using the area under the receiver operating characteristic curve (ROC-AUC), and an optimal cutoff will be determined. The resulting cutoff will subsequently be used to identify subclinical respiratory impairment in asymptomatic/presymptomatic ALS gene carriers. |
During the single study visit
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Fractional Anisotropy of the Brainstem and Cervical Spinal Cord
時間枠：During the single study visit
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Fractional anisotropy (FA) will be derived from diffusion tensor imaging of the brainstem and cervical spinal cord to evaluate microstructural abnormalities associated with ALS. FA will be compared among healthy controls and asymptomatic/presymptomatic ALS gene carriers who test positive or negative for automatic breathing impairment. |
During the single study visit
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Axial Diffusivity of the Brainstem and Cervical Spinal Cord
時間枠：During the single study visit
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Axial diffusivity will be derived from diffusion tensor imaging of the brainstem and cervical spinal cord to evaluate microstructural abnormalities associated with ALS. Measurements will be compared among healthy controls and asymptomatic/presymptomatic ALS gene carriers who test positive or negative for automatic breathing impairment. |
During the single study visit
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Radial Diffusivity of the Brainstem and Cervical Spinal Cord
時間枠：During the single study visit
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Radial diffusivity will be derived from diffusion tensor imaging of the brainstem and cervical spinal cord to evaluate microstructural abnormalities associated with ALS. Measurements will be compared among healthy controls and asymptomatic/presymptomatic ALS gene carriers who test positive or negative for automatic breathing impairment. |
During the single study visit
|
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Mean Diffusivity of the Brainstem and Cervical Spinal Cord
時間枠：During the single study visit
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Mean diffusivity will be derived from diffusion tensor imaging of the brainstem and cervical spinal cord to evaluate microstructural abnormalities associated with ALS. Measurements will be compared among healthy controls and asymptomatic/presymptomatic ALS gene carriers who test positive or negative for automatic breathing impairment. |
During the single study visit
|
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Plasma Neurofilament Light Chain (Nf-L) Level
時間枠：During the single study visit
|
Neurofilament light chain (Nf-L) levels in plasma will be measured as a blood-based marker of neurodegeneration. Plasma Nf-L levels will be compared among healthy controls and asymptomatic/presymptomatic ALS gene carriers who test positive or negative for automatic breathing impairment to determine whether respiratory impairment is associated with greater evidence of neurodegeneration. |
During the single study visit
|
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Serum Neurofilament Light Chain (Nf-L) Level
時間枠：During the single study visit.
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Neurofilament light chain (Nf-L) levels in serum will be measured as a blood-based marker of neurodegeneration. Serum Nf-L levels will be evaluated in relation to automatic breathing impairment and compared across study groups as an additional blood-based biomarker of ALS-related neurodegeneration. |
During the single study visit.
|
協力者と研究者
出版物と役立つリンク
一般刊行物
- Lechtzin N, Wiener CM, Clawson L, Chaudhry V, Diette GB. Hospitalization in amyotrophic lateral sclerosis: causes, costs, and outcomes. Neurology. 2001 Mar 27;56(6):753-7. doi: 10.1212/wnl.56.6.753.
- American Thoracic Society/European Respiratory Society. ATS/ERS Statement on respiratory muscle testing. Am J Respir Crit Care Med. 2002 Aug 15;166(4):518-624. doi: 10.1164/rccm.166.4.518. No abstract available.
- Laveneziana P, Albuquerque A, Aliverti A, Babb T, Barreiro E, Dres M, Dube BP, Fauroux B, Gea J, Guenette JA, Hudson AL, Kabitz HJ, Laghi F, Langer D, Luo YM, Neder JA, O'Donnell D, Polkey MI, Rabinovich RA, Rossi A, Series F, Similowski T, Spengler CM, Vogiatzis I, Verges S. ERS statement on respiratory muscle testing at rest and during exercise. Eur Respir J. 2019 Jun 13;53(6):1801214. doi: 10.1183/13993003.01214-2018. Print 2019 Jun.
- Parthasarathy S, Jubran A, Laghi F, Tobin MJ. Sternomastoid, rib cage, and expiratory muscle activity during weaning failure. J Appl Physiol (1985). 2007 Jul;103(1):140-7. doi: 10.1152/japplphysiol.00904.2006. Epub 2007 Mar 29.
- Khalil M, Teunissen CE, Otto M, Piehl F, Sormani MP, Gattringer T, Barro C, Kappos L, Comabella M, Fazekas F, Petzold A, Blennow K, Zetterberg H, Kuhle J. Neurofilaments as biomarkers in neurological disorders. Nat Rev Neurol. 2018 Oct;14(10):577-589. doi: 10.1038/s41582-018-0058-z.
- Gaetani L, Blennow K, Calabresi P, Di Filippo M, Parnetti L, Zetterberg H. Neurofilament light chain as a biomarker in neurological disorders. J Neurol Neurosurg Psychiatry. 2019 Aug;90(8):870-881. doi: 10.1136/jnnp-2018-320106. Epub 2019 Apr 9.
- Butler JE. Drive to the human respiratory muscles. Respir Physiol Neurobiol. 2007 Nov 15;159(2):115-26. doi: 10.1016/j.resp.2007.06.006. Epub 2007 Jun 17.
- Shefner JM, Al-Chalabi A, Baker MR, Cui LY, de Carvalho M, Eisen A, Grosskreutz J, Hardiman O, Henderson R, Matamala JM, Mitsumoto H, Paulus W, Simon N, Swash M, Talbot K, Turner MR, Ugawa Y, van den Berg LH, Verdugo R, Vucic S, Kaji R, Burke D, Kiernan MC. A proposal for new diagnostic criteria for ALS. Clin Neurophysiol. 2020 Aug;131(8):1975-1978. doi: 10.1016/j.clinph.2020.04.005. Epub 2020 Apr 19. No abstract available.
- Benatar M, Wuu J, Lombardi V, Jeromin A, Bowser R, Andersen PM, Malaspina A. Neurofilaments in pre-symptomatic ALS and the impact of genotype. Amyotroph Lateral Scler Frontotemporal Degener. 2019 Nov;20(7-8):538-548. doi: 10.1080/21678421.2019.1646769. Epub 2019 Aug 21.
- Telias I, Junhasavasdikul D, Rittayamai N, Piquilloud L, Chen L, Ferguson ND, Goligher EC, Brochard L. Airway Occlusion Pressure As an Estimate of Respiratory Drive and Inspiratory Effort during Assisted Ventilation. Am J Respir Crit Care Med. 2020 May 1;201(9):1086-1098. doi: 10.1164/rccm.201907-1425OC.
- Whitelaw WA, Derenne JP, Milic-Emili J. Occlusion pressure as a measure of respiratory center output in conscious man. Respir Physiol. 1975 Mar;23(2):181-99. doi: 10.1016/0034-5687(75)90059-6.
- Vose AK, Welch JF, Nair J, Dale EA, Fox EJ, Muir GD, Trumbower RD, Mitchell GS. Therapeutic acute intermittent hypoxia: A translational roadmap for spinal cord injury and neuromuscular disease. Exp Neurol. 2022 Jan;347:113891. doi: 10.1016/j.expneurol.2021.113891. Epub 2021 Oct 9.
- Saracino D, Dorgham K, Camuzat A, Rinaldi D, Rametti-Lacroux A, Houot M, Clot F, Martin-Hardy P, Jornea L, Azuar C, Migliaccio R, Pasquier F, Couratier P, Auriacombe S, Sauvee M, Boutoleau-Bretonniere C, Pariente J, Didic M, Hannequin D, Wallon D; French Research Network on FTD/FTD-ALS; PREV-DEMALS and Predict-PGRN study groups; Colliot O, Dubois B, Brice A, Levy R, Forlani S, Le Ber I. Plasma NfL levels and longitudinal change rates in C9orf72 and GRN-associated diseases: from tailored references to clinical applications. J Neurol Neurosurg Psychiatry. 2021 Dec;92(12):1278-1288. doi: 10.1136/jnnp-2021-326914. Epub 2021 Aug 4.
- Rojas JC, Wang P, Staffaroni AM, Heller C, Cobigo Y, Wolf A, Goh SM, Ljubenkov PA, Heuer HW, Fong JC, Taylor JB, Veras E, Song L, Jeromin A, Hanlon D, Yu L, Khinikar A, Sivasankaran R, Kieloch A, Valentin MA, Karydas AM, Mitic LL, Pearlman R, Kornak J, Kramer JH, Miller BL, Kantarci K, Knopman DS, Graff-Radford N, Petrucelli L, Rademakers R, Irwin DJ, Grossman M, Ramos EM, Coppola G, Mendez MF, Bordelon Y, Dickerson BC, Ghoshal N, Huey ED, Mackenzie IR, Appleby BS, Domoto-Reilly K, Hsiung GR, Toga AW, Weintraub S, Kaufer DI, Kerwin D, Litvan I, Onyike CU, Pantelyat A, Roberson ED, Tartaglia MC, Foroud T, Chen W, Czerkowicz J, Graham DL, van Swieten JC, Borroni B, Sanchez-Valle R, Moreno F, Laforce R, Graff C, Synofzik M, Galimberti D, Rowe JB, Masellis M, Finger E, Vandenberghe R, de Mendonca A, Tagliavini F, Santana I, Ducharme S, Butler CR, Gerhard A, Levin J, Danek A, Otto M, Sorbi S, Cash DM, Convery RS, Bocchetta M, Foiani M, Greaves CV, Peakman G, Russell L, Swift I, Todd E, Rohrer JD, Boeve BF, Rosen HJ, Boxer AL; ALLFTD and GENFI consortia. Plasma Neurofilament Light for Prediction of Disease Progression in Familial Frontotemporal Lobar Degeneration. Neurology. 2021 May 4;96(18):e2296-e2312. doi: 10.1212/WNL.0000000000011848. Epub 2021 Apr 7.
- Bourke SC, Tomlinson M, Williams TL, Bullock RE, Shaw PJ, Gibson GJ. Effects of non-invasive ventilation on survival and quality of life in patients with amyotrophic lateral sclerosis: a randomised controlled trial. Lancet Neurol. 2006 Feb;5(2):140-7. doi: 10.1016/S1474-4422(05)70326-4.
- Miller RG, Jackson CE, Kasarskis EJ, England JD, Forshew D, Johnston W, Kalra S, Katz JS, Mitsumoto H, Rosenfeld J, Shoesmith C, Strong MJ, Woolley SC; Quality Standards Subcommittee of the American Academy of Neurology. Practice parameter update: the care of the patient with amyotrophic lateral sclerosis: drug, nutritional, and respiratory therapies (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2009 Oct 13;73(15):1218-26. doi: 10.1212/WNL.0b013e3181bc0141.
- Raz E, Bester M, Sigmund EE, Tabesh A, Babb JS, Jaggi H, Helpern J, Mitnick RJ, Inglese M. A better characterization of spinal cord damage in multiple sclerosis: a diffusional kurtosis imaging study. AJNR Am J Neuroradiol. 2013 Sep;34(9):1846-52. doi: 10.3174/ajnr.A3512. Epub 2013 Apr 11.
- Tabesh A, Jensen JH, Ardekani BA, Helpern JA. Estimation of tensors and tensor-derived measures in diffusional kurtosis imaging. Magn Reson Med. 2011 Mar;65(3):823-36. doi: 10.1002/mrm.22655. Epub 2010 Oct 28.
- De Leener B, Levy S, Dupont SM, Fonov VS, Stikov N, Louis Collins D, Callot V, Cohen-Adad J. SCT: Spinal Cord Toolbox, an open-source software for processing spinal cord MRI data. Neuroimage. 2017 Jan 15;145(Pt A):24-43. doi: 10.1016/j.neuroimage.2016.10.009. Epub 2016 Oct 5.
- Ilieva H, Vullaganti M, Kwan J. Advances in molecular pathology, diagnosis, and treatment of amyotrophic lateral sclerosis. BMJ. 2023 Oct 27;383:e075037. doi: 10.1136/bmj-2023-075037.
- Middleton DM, Shahrampour S, Krisa L, Liu W, Nair G, Jacobson S, Conklin CJ, Alizadeh M, Faro SH, Mulcahey MJ, Mohamed FB. Correlations of diffusion tensor imaging and clinical measures with spinal cord cross-sectional area measurements in pediatric spinal cord injury patients. J Spinal Cord Med. 2023 Nov;46(6):950-957. doi: 10.1080/10790268.2021.1997027. Epub 2021 Dec 2.
- Shahrampour S, De Leener B, Alizadeh M, Middleton D, Krisa L, Flanders AE, Faro SH, Cohen-Adad J, Mohamed FB. Atlas-Based Quantification of DTI Measures in a Typically Developing Pediatric Spinal Cord. AJNR Am J Neuroradiol. 2021 Sep;42(9):1727-1734. doi: 10.3174/ajnr.A7221. Epub 2021 Jul 29.
- Fisher J, Alizadeh M, Middleton D, Matias CM, Mulcahey MJ, Calhoun-Thielen C, Mohamed FB, Krisa L. Brain White Matter Abnormality Induced by Chronic Spinal Cord Injury in the Pediatric Population: A Preliminary Tract-based Spatial Statistic Study. Top Spinal Cord Inj Rehabil. 2021 Fall;27(4):1-13. doi: 10.46292/sci20-00018. Epub 2021 Jun 4.
- Alizadeh M, Manmatharayan AR, Johnston T, Thalheimer S, Finley M, Detloff M, Sharan A, Harrop J, Newburg A, Krisa L, Mohamed FB. Graph theoretical structural connectome analysis of the brain in patients with chronic spinal cord injury: preliminary investigation. Spinal Cord Ser Cases. 2021 Jul 17;7(1):60. doi: 10.1038/s41394-021-00424-3.
- Foust KD, Salazar DL, Likhite S, Ferraiuolo L, Ditsworth D, Ilieva H, Meyer K, Schmelzer L, Braun L, Cleveland DW, Kaspar BK. Therapeutic AAV9-mediated suppression of mutant SOD1 slows disease progression and extends survival in models of inherited ALS. Mol Ther. 2013 Dec;21(12):2148-59. doi: 10.1038/mt.2013.211. Epub 2013 Sep 6.
- Ilieva HS, Yamanaka K, Malkmus S, Kakinohana O, Yaksh T, Marsala M, Cleveland DW. Mutant dynein (Loa) triggers proprioceptive axon loss that extends survival only in the SOD1 ALS model with highest motor neuron death. Proc Natl Acad Sci U S A. 2008 Aug 26;105(34):12599-604. doi: 10.1073/pnas.0805422105. Epub 2008 Aug 21.
- Nair J, Welch JF, Marciante AB, Hou T, Lu Q, Fox EJ, Mitchell GS. APOE4, Age, and Sex Regulate Respiratory Plasticity Elicited by Acute Intermittent Hypercapnic-Hypoxia. Function (Oxf). 2023 Jun 13;4(5):zqad026. doi: 10.1093/function/zqad026. eCollection 2023.
- Welch JF, Nair J, Argento PJ, Mitchell GS, Fox EJ. Acute intermittent hypercapnic-hypoxia elicits central neural respiratory motor plasticity in humans. J Physiol. 2022 May;600(10):2515-2533. doi: 10.1113/JP282822. Epub 2022 Apr 28.
- Ahmad S, Srivastava RK, Singh P, Naik UP, Srivastava AK. Role of Extracellular Vesicles in Glia-Neuron Intercellular Communication. Front Mol Neurosci. 2022 Apr 13;15:844194. doi: 10.3389/fnmol.2022.844194. eCollection 2022.
- Lizarraga-Valderrama LR, Sheridan GK. Extracellular vesicles and intercellular communication in the central nervous system. FEBS Lett. 2021 May;595(10):1391-1410. doi: 10.1002/1873-3468.14074. Epub 2021 Apr 3.
- Gafson AR, Barthelemy NR, Bomont P, Carare RO, Durham HD, Julien JP, Kuhle J, Leppert D, Nixon RA, Weller RO, Zetterberg H, Matthews PM. Neurofilaments: neurobiological foundations for biomarker applications. Brain. 2020 Jul 1;143(7):1975-1998. doi: 10.1093/brain/awaa098.
- Kaur M, Fusco S, Van den Broek B, Aseervatham J, Rostami A, Iacovitti L, Grassi C, Lukomska B, Srivastava AK. Most recent advances and applications of extracellular vesicles in tackling neurological challenges. Med Res Rev. 2024 Jul;44(4):1923-1966. doi: 10.1002/med.22035. Epub 2024 Mar 18.
- Weydt P, Oeckl P, Huss A, Muller K, Volk AE, Kuhle J, Knehr A, Andersen PM, Prudlo J, Steinacker P, Weishaupt JH, Ludolph AC, Otto M. Neurofilament levels as biomarkers in asymptomatic and symptomatic familial amyotrophic lateral sclerosis. Ann Neurol. 2016 Jan;79(1):152-8. doi: 10.1002/ana.24552. Epub 2015 Dec 17.
- van der Ende EL, Meeter LH, Poos JM, Panman JL, Jiskoot LC, Dopper EGP, Papma JM, de Jong FJ, Verberk IMW, Teunissen C, Rizopoulos D, Heller C, Convery RS, Moore KM, Bocchetta M, Neason M, Cash DM, Borroni B, Galimberti D, Sanchez-Valle R, Laforce R Jr, Moreno F, Synofzik M, Graff C, Masellis M, Carmela Tartaglia M, Rowe JB, Vandenberghe R, Finger E, Tagliavini F, de Mendonca A, Santana I, Butler C, Ducharme S, Gerhard A, Danek A, Levin J, Otto M, Frisoni GB, Cappa S, Pijnenburg YAL, Rohrer JD, van Swieten JC; Genetic Frontotemporal dementia Initiative (GENFI). Serum neurofilament light chain in genetic frontotemporal dementia: a longitudinal, multicentre cohort study. Lancet Neurol. 2019 Dec;18(12):1103-1111. doi: 10.1016/S1474-4422(19)30354-0.
- Khalil M, Pirpamer L, Hofer E, Voortman MM, Barro C, Leppert D, Benkert P, Ropele S, Enzinger C, Fazekas F, Schmidt R, Kuhle J. Serum neurofilament light levels in normal aging and their association with morphologic brain changes. Nat Commun. 2020 Feb 10;11(1):812. doi: 10.1038/s41467-020-14612-6.
- Jaromirska J, Kaczmarski P, Strzelecki D, Sochal M, Bialasiewicz P, Gabryelska A. Shedding light on neurofilament involvement in cognitive decline in obstructive sleep apnea and its possible role as a biomarker. Front Psychiatry. 2023 Nov 30;14:1289367. doi: 10.3389/fpsyt.2023.1289367. eCollection 2023.
- Bridel C, van Wieringen WN, Zetterberg H, Tijms BM, Teunissen CE; and the NFL Group; Alvarez-Cermeno JC, Andreasson U, Axelsson M, Backstrom DC, Bartos A, Bjerke M, Blennow K, Boxer A, Brundin L, Burman J, Christensen T, Fialova L, Forsgren L, Frederiksen JL, Gisslen M, Gray E, Gunnarsson M, Hall S, Hansson O, Herbert MK, Jakobsson J, Jessen-Krut J, Janelidze S, Johannsson G, Jonsson M, Kappos L, Khademi M, Khalil M, Kuhle J, Landen M, Leinonen V, Logroscino G, Lu CH, Lycke J, Magdalinou NK, Malaspina A, Mattsson N, Meeter LH, Mehta SR, Modvig S, Olsson T, Paterson RW, Perez-Santiago J, Piehl F, Pijnenburg YAL, Pyykko OT, Ragnarsson O, Rojas JC, Romme Christensen J, Sandberg L, Scherling CS, Schott JM, Sellebjerg FT, Simone IL, Skillback T, Stilund M, Sundstrom P, Svenningsson A, Tortelli R, Tortorella C, Trentini A, Troiano M, Turner MR, van Swieten JC, Vagberg M, Verbeek MM, Villar LM, Visser PJ, Wallin A, Weiss A, Wikkelso C, Wild EJ. Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology: A Systematic Review and Meta-analysis. JAMA Neurol. 2019 Sep 1;76(9):1035-1048. doi: 10.1001/jamaneurol.2019.1534.
- Querin G, Bede P, El Mendili MM, Li M, Pelegrini-Issac M, Rinaldi D, Catala M, Saracino D, Salachas F, Camuzat A, Marchand-Pauvert V, Cohen-Adad J, Colliot O, Le Ber I, Pradat PF; Predict to Prevent Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis Study Group. Presymptomatic spinal cord pathology in c9orf72 mutation carriers: A longitudinal neuroimaging study. Ann Neurol. 2019 Aug;86(2):158-167. doi: 10.1002/ana.25520. Epub 2019 Jun 27.
- Walhout R, Schmidt R, Westeneng HJ, Verstraete E, Seelen M, van Rheenen W, de Reus MA, van Es MA, Hendrikse J, Veldink JH, van den Heuvel MP, van den Berg LH. Brain morphologic changes in asymptomatic C9orf72 repeat expansion carriers. Neurology. 2015 Nov 17;85(20):1780-8. doi: 10.1212/WNL.0000000000002135. Epub 2015 Oct 23.
- Papma JM, Jiskoot LC, Panman JL, Dopper EG, den Heijer T, Donker Kaat L, Pijnenburg YAL, Meeter LH, van Minkelen R, Rombouts SARB, van Swieten JC. Cognition and gray and white matter characteristics of presymptomatic C9orf72 repeat expansion. Neurology. 2017 Sep 19;89(12):1256-1264. doi: 10.1212/WNL.0000000000004393. Epub 2017 Aug 30.
- Bede P, Hardiman O. Longitudinal structural changes in ALS: a three time-point imaging study of white and gray matter degeneration. Amyotroph Lateral Scler Frontotemporal Degener. 2018 May;19(3-4):232-241. doi: 10.1080/21678421.2017.1407795. Epub 2017 Dec 7.
- Floeter MK, Danielian LE, Braun LE, Wu T. Longitudinal diffusion imaging across the C9orf72 clinical spectrum. J Neurol Neurosurg Psychiatry. 2018 Jan;89(1):53-60. doi: 10.1136/jnnp-2017-316799. Epub 2017 Oct 20.
- Vold ML, Aasebo U, Wilsgaard T, Melbye H. Low oxygen saturation and mortality in an adult cohort: the Tromso study. BMC Pulm Med. 2015 Feb 12;15:9. doi: 10.1186/s12890-015-0003-5.
- Morgan BJ, Adrian R, Bates ML, Dopp JM, Dempsey JA. Quantifying hypoxia-induced chemoreceptor sensitivity in the awake rodent. J Appl Physiol (1985). 2014 Oct 1;117(7):816-24. doi: 10.1152/japplphysiol.00484.2014. Epub 2014 Jul 31.
- Shea SA. Behavioural and arousal-related influences on breathing in humans. Exp Physiol. 1996 Jan;81(1):1-26. doi: 10.1113/expphysiol.1996.sp003911.
- Pinto S, Swash M, De Carvalho M. Mouth occlusion pressure at 100ms (P0.1) as a respiratory biomarker in amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2021 Feb;22(1-2):53-60. doi: 10.1080/21678421.2020.1821061. Epub 2020 Sep 21.
- Seven YB, Mantilla CB, Sieck GC. Recruitment of rat diaphragm motor units across motor behaviors with different levels of diaphragm activation. J Appl Physiol (1985). 2014 Dec 1;117(11):1308-16. doi: 10.1152/japplphysiol.01395.2013. Epub 2014 Sep 25.
- Gandevia SC, Rothwell JC. Activation of the human diaphragm from the motor cortex. J Physiol. 1987 Mar;384:109-18. doi: 10.1113/jphysiol.1987.sp016445.
- Evans KC, Shea SA, Saykin AJ. Functional MRI localisation of central nervous system regions associated with volitional inspiration in humans. J Physiol. 1999 Oct 15;520 Pt 2(Pt 2):383-92. doi: 10.1111/j.1469-7793.1999.00383.x.
- NATHAN PW. THE DESCENDING RESPIRATORY PATHWAY IN MAN. J Neurol Neurosurg Psychiatry. 1963 Dec;26(6):487-99. doi: 10.1136/jnnp.26.6.487. No abstract available.
- Aminoff MJ, Sears TA. Spinal integration of segmental, cortical and breathing inputs to thoracic respiratory motoneurones. J Physiol. 1971 Jun;215(2):557-75. doi: 10.1113/jphysiol.1971.sp009485.
- Varga AG, Maletz SN, Bateman JT, Reid BT, Levitt ES. Neurochemistry of the Kolliker-Fuse nucleus from a respiratory perspective. J Neurochem. 2021 Jan;156(1):16-37. doi: 10.1111/jnc.15041. Epub 2020 Jun 10.
- Dobbins EG, Feldman JL. Brainstem network controlling descending drive to phrenic motoneurons in rat. J Comp Neurol. 1994 Sep 1;347(1):64-86. doi: 10.1002/cne.903470106.
- Feldman JL, Mitchell GS, Nattie EE. Breathing: rhythmicity, plasticity, chemosensitivity. Annu Rev Neurosci. 2003;26:239-66. doi: 10.1146/annurev.neuro.26.041002.131103. Epub 2003 Feb 13.
- Benatar M, Wuu J, McHutchison C, Postuma RB, Boeve BF, Petersen R, Ross CA, Rosen H, Arias JJ, Fradette S, McDermott MP, Shefner J, Stanislaw C, Abrahams S, Cosentino S, Andersen PM, Finkel RS, Granit V, Grignon AL, Rohrer JD, McMillan CT, Grossman M, Al-Chalabi A, Turner MR; First International Pre-Symptomatic ALS Workshop. Preventing amyotrophic lateral sclerosis: insights from pre-symptomatic neurodegenerative diseases. Brain. 2022 Mar 29;145(1):27-44. doi: 10.1093/brain/awab404.
- Nichols NL, Van Dyke J, Nashold L, Satriotomo I, Suzuki M, Mitchell GS. Ventilatory control in ALS. Respir Physiol Neurobiol. 2013 Nov 1;189(2):429-37. doi: 10.1016/j.resp.2013.05.016. Epub 2013 May 18.
- Sferrazza Papa GF, Pellegrino GM, Di Marco F, Corbo M, Centanni S. Predicting Survival in Amyotrophic Lateral Sclerosis: Should We Move Forward from Vital Capacity? Am J Respir Crit Care Med. 2017 Jan 1;195(1):144-145. doi: 10.1164/rccm.201609-1838LE. No abstract available.
- Polkey MI, Lyall RA, Yang K, Johnson E, Leigh PN, Moxham J. Respiratory Muscle Strength as a Predictive Biomarker for Survival in Amyotrophic Lateral Sclerosis. Am J Respir Crit Care Med. 2017 Jan 1;195(1):86-95. doi: 10.1164/rccm.201604-0848OC.
- Berlowitz DJ, Howard ME, Fiore JF Jr, Vander Hoorn S, O'Donoghue FJ, Westlake J, Smith A, Beer F, Mathers S, Talman P. Identifying who will benefit from non-invasive ventilation in amyotrophic lateral sclerosis/motor neurone disease in a clinical cohort. J Neurol Neurosurg Psychiatry. 2016 Mar;87(3):280-6. doi: 10.1136/jnnp-2014-310055. Epub 2015 Apr 9.
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- 22D.834
- 1R21NS145175-01A1 (米国 NIH グラント/契約)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
De-identified individual participant data underlying the results reported in study publications will be shared. Data may include demographic and clinical data, functional respiratory measurements, brainstem and spinal cord MRI data, and blood biomarker data, including neurofilament light chain measurements. Data will be shared without direct participant identifiers and in accordance with applicable data use agreements and institutional requirements.
IPD 共有時間枠
Data will become available at the time of publication or by the end of the funding period, whichever occurs first. Data supporting a publication may be made available when the associated preprint is available. The duration of data preservation will be determined by the applicable repository and/or Thomas Jefferson University.
IPD 共有アクセス基準
De-identified data will be available to qualified investigators for research purposes. Requests for controlled-access data will be reviewed by a data-sharing committee for scientific merit and feasibility. A Data Use Agreement will be required before transfer of controlled-access data. Investigators receiving data must agree to use the data only for research purposes, not attempt to identify individual participants, and maintain appropriate data security. Public imaging datasets may be accessed through the applicable imaging repository.
IPD 共有サポート情報タイプ
- STUDY_PROTOCOL
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。