Boylan, L. S.

Chio, A.

English

Institutional Research Information System University of Turin

EDITORIALDivining progression in Parkinson disease witha blood testNfLLaura S. Boylan, MD, and Adriano Chiò, MD, FAANNeurology® 2019;93:471-472. doi:10.1212/WNL.0000000000008087CorrespondenceDr. Boylanlaura.boylan@med.nyu.eduIn their article in this issue of Neurology®, Lin and colleagues1 provide compelling evidence forthe utility of a neurofilament light chain (NfL) blood test in predicting progression in Parkinsondisease (PD) and in distinguishing PD from multisystem atrophy (MSA). If confirmed byindependent studies, this would be a major advance for clinical and basic research. Such a testalso may have complex consequences for clinical care.Available tools for prognosis in PD are limited. Clinical factors, including advanced disease atdiagnosis, male sex, and advanced age, are associated with more rapid progression.2 The utilityof classifying PD phenotypes into tremor-predominant relatively benign, compared to postural-instability gait disorder relatively more rapidly progressive, has been questioned.3 Geneticvariation and CSF biomarkers (mainly α-synuclein) have shown utility as biomarkers of PDprogression.2,4 Imaging and multimodal risk modeling may also be useful.2,4 However, none ofthese biomarkers are universally accepted, and some are limited to specific patient populations.Nf L is a an abundant neuronal cytoskeletal protein. There has been much interest in NfL asa biomarker for neurologic injury, particularly in Alzheimer disease, inherited peripheral neu-ropathy, multiple sclerosis, amyotrophic lateral sclerosis, and acute brain injury.5 Most of thisresearch has been based onNfL as measured from the CSF.More recently, a good correlation ofNfL levels in CSF and serum has been reported.5The Chin et al. study prospectively enrolled 178 participants, including 116 with PD, 22 withMSA, and 40 healthy controls. The study cohort may be small for stroke, but for PD/MSA, thisis a substantially sized cohort, and follow-up averaged 3 years. The correlation of motor andcognitive status andNfL was found both cross-sectionally and longitudinally. In addition, serumNfL levels distinguished MSA from PD. The authors were able to establish a cutoff level thatseparated participants with PD with stable disease at 3 years from those who progressed. Therewas marked divergence in Kaplan-Meier–plotted clinical trajectories for both motor andcognitive symptoms. At the end of the 3-year study, motor progression occurred among allparticipants with PD with baseline NfL levels ≥21.84 pg/mL, while only about half of patientswith lower NfL levels showed progression. Cognitive progression occurred by the end of thestudy period in all participants with NfL ≥18.34 pg/mL and among approximately one-third ofthose with lower NfL levels. Hence, NfL levels more robustly foretell bad than good news.A caveat here is that the definitions of motor and mental decline on the United Parkinson’sDisease Rating Scale part III (decline of >2 points) and Mini-Mental State Examination (<26points) were not necessarily of a magnitude that would reach clinical relevance; in fact, studiesdesigned to address the changes that make clinically important differences using these measuressuggest that these changes may not be clinically important.6,7 However, over the 3-year periodof the study, the difference between progressors and nonprogressors was increased. Furtherlongitudinal follow-up and confirmation are needed to determine whether these divergenttrajectories persist.From Bellevue Hospital (L.S.B.); New York University School of Medicine (L.S.B.); Albany-Stratton VA Medical Center, NY (L.S.B.); Essentia Health, Duluth, MN (L.S.B.); and “Rita LeviMontalcini” Department of Neuroscience (A.C.), University of Turin, Italy.Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the editorial.RELATED ARTICLEBloodNfL: A biomarker fordisease severity andprogression in ParkinsondiseasePage 482Copyright © 2019 American Academy of Neurology 471Copyright © 2019 American Academy of Neurology. Unauthorized reproduction of this article is prohibited.While NfL levels distinguished PD from healthy controls andpatients with MSA from those with PD, it needs to be em-phasized that all participants met clinical diagnostic criteria forPD orMSA by the time of entry into the study. Hence, while itraises hopes for the future, the present study was not designedto address the usefulness of NfL for early diagnosis of eitherPD or MSA.Emerging technologies to predict future risk are not them-selves without risk.8 Experience from other tests to predictneurologic diseases, while not fully analogous, suggest that,with careful consideration, not all persons want to know whatthe future holds and that predictive testing can have adverseeffects even for those whose results yield “good news.”The model for Huntington disease involving extensive pretestand posttest counseling has been proposed for other types ofpredictive testing.8 Advances in technology will make morepredictive tests available. At the same time, an increasinglyskeptical public is leaning away from “whatever you say, doc”and toward other information sources, including the internet.Whole-body CTs and MRIs are available for “screening” onthe private market. Similarly, genetic profiles are proposed byprivate companies as being able to identify a large range ofrisks, including hereditary cancers and degenerative diseases.Risk profiles, albeit of uncertain accuracy, are available directlyto consumer and are widely used.9 These are tricky waters tonavigate. Further research is needed not only to define thevalue of NfL as a surrogate biomarker for PD progression butalso to understand the clinical import and social ramificationsof the availability of predictive testing in neurology. If con-firmed, the present data would suggest that the practicingneurologist would have a test to robustly predict progressionbut likely not to reassure nonprogressors.Study fundingNo targeted funding reported.DisclosureThe authors report no disclosures. Go to Neurology.org/Nfor full disclosures.References1. Lin CH, Li CH, Yang KC, et al. Blood NfL: a biomarker for disease severity andprogression in Parkinson disease. Neurology 2019;93:e1104–e1111.2. Blauwendraat C, Bandrés-Ciga S, Singleton AB. Predicting progression in patientswith Parkinson’s disease. Lancet Neurol 2017;16:860–862.3. Fereshtehnejad SM, Postuma RB. Subtypes of Parkinson’s disease: what do they tellus about disease progression? Curr Neurol Neurosci Rep 2017;17:34.4. Parnetti L, Gaetani L, Eusebi P, et al. CSF and blood biomarkers for Parkinson’sdisease. Lancet Neurol 2019;18:573–586.5. Bacioglu M,Maia LF, Preische O, et al. Neurofilament light chain in blood and CSF asmarker of disease progression in mouse models and in neurodegenerative diseases.Neuron 2016;91:494–496.6. Horváth K, Aschermann Z, Ács P, et al. Minimal clinically important difference on themotor examination part of MDS-UPDRS. Parkinsonism Relat Disord 2015;21:1421–1426.7. Feeney J, Savva GM, O’Regan C, King-Kallimanis B, Cronin H, Kenny RA. Mea-surement error, reliability, and minimum detectable change in the Mini-Mental StateExamination, Montreal Cognitive Assessment, and Color Trails Test among com-munity living middle-aged and older adults. J Alzheimers Dis 2016;53:1107–1114.8. Hayden MR. Predictive testing for Huntington’s disease: a universal model? LancetNeurol 2003;2:141–142.9. Check Hayden E. The rise and fall and rise again of 23andMe. Nature 2017;550:174–177.472 Neurology | Volume 93, Number 11 | September 10, 2019 Neurology.org/NCopyright © 2019 American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

Divining progression in Parkinson disease with a blood test: NfL

https://iris.unito.it/retrieve/handle/2318/1720144/555790/Neurology%202019%20-%20Boylan%20%26amp%3b%20Chio%20-%20Divining%20progression%20of%20PD%20with%20a%20blood%20test.pdf

Divining progression in Parkinson disease with a blood test: NfL

Abstract

Similar works

Full text

Available Versions

Institutional Research Information System University of Turin