Spontaneous eye blinking as a diagnostic and prognostic marker in disorders of consciousness: Protocol of an international multicentre longitudinal study
Restricted accessResearch articleFirst published online December, 2024
Spontaneous eye blinking as a diagnostic and prognostic marker in disorders of consciousness: Protocol of an international multicentre longitudinal study
Diagnostic and prognostic decision-making in patients with Disorders of Consciousness (DoC) is challenging. It has been suggested that spontaneous eye blink rate is an index of patients’ level of consciousness easy to detect in clinical practice. Further blinking features (i.e., amplitude, duration, variability in intervals between blinks) may change as a function of cognitive load, but have not been investigated in patients with DoC.
OBJECTIVE
This multicentre, longitudinal study aims at exploring the diagnostic and prognostic value of spontaneous eye blinking features in DoC.
METHODS
Eight European medical institutions will enrol consecutively admitted adult patients with DoC. Within two weeks from study entry demographic, anamnestic and clinical data will be collected. Moreover, patients will undergo two 20-minute EEG-EOG recordings at rest, to collect blinking features and EEG activity. A clinical follow-up will be performed after 6 months. A group of healthy individuals will be enrolled for reference.
RESULTS
Possible differences in blink features between patients and the reference group, differences across diagnostic sub-groups, and correlations between blinking features and clinical outcome will be investigated.
CONCLUSION
The results of this study might help clinicians to reduce misdiagnosis rate in DoC and provide useful information for prognostication and care pathway plan.
AdamsJ. H.GrahamD. I.JennettB. (2000). The neuropathology of the vegetative state after an acute brain insult. Brain, 123(Pt 7), 1327–1338. https://doi.org/10.1093/brain/123.7.1327.
2.
American Congress of Rehabilitation Medicine, Brain Injury-Interdisciplinary Special Interest Group, Disorders of Consciousness Task Force, SeelR. T.ShererM.WhyteJ.KatzD. I.GiacinoJ. T.RosenbaumA. M.HammondF. M.KalmarK.PapeT. L.ZafonteR.BiesterR. C.KaelinD.KeanJ.ZaslerN. (2010). Assessment scales for disorders of consciousness: Evidence-based recommendations for clinical practice and research. Archives of Physical Medicine and Rehabilitation, 91(12), 1795–1813. https://doi.org/10.1016/j.apmr.2010.07.218.
3.
AnnenJ.FilippiniM. M.BoninE.CassolH.AubinetC.CarrièreM.GosseriesO.ThibautA.BarraA.WolffA.SanzL. R. D.MartialC.LaureysS.ChatelleC. (2019). Diagnostic accuracy of the CRS-R index in patients with disorders of consciousness. Brain Injury, 33(11), 1409–1412. https://doi.org/10.1080/02699052.2019.1644376.
4.
BarbaraN.CamilleriT. A.CamilleriK. P. (2019). EOG-based eye movement detection and gaze estimation for an asynchronous virtual keyboard. Biomedical Signal Processing and Control, 47, 159–167.
BonfiglioL.CarbonciniM. C.BongioanniP.AndreP.MinichilliF.ForniM.RossiB. (2005). Spontaneous blinking behaviour in persistent vegetative and minimally conscious states: Relationships with evolution and outcome. Brain Research Bulletin, 68(3), 163–170. https://doi.org/10.1016/j.brainresbull.2005.08.003.
7.
BrunoM. A.VanhaudenhuyseA.ThibautA.MoonenG.LaureysS. (2011). From unresponsive wakefulness to minimally conscious PLUS and functional locked-in syndromes: Recent advances in our understanding of disorders of consciousness. Journal of Neurology, 258(7), 1373–1384. https://doi.org/10.1007/s00415-011-6114-x.
8.
CalabròR. S.ChilluraA.BilleriL.CannavòA.BudaA.MoloniaF.ManuliA.BramantiP.NaroA. (2020). Peri-personal space tracing by hand-blink reflex modulation in patients with chronic disorders of consciousness. Scientific Reports, 10(1), 1712. https://doi.org/10.1038/s41598-020-58625-z.
9.
CandelieriA.CorteseM. D.DolceG.RiganelloF.SannitaW. G. (2011). Visual pursuit: Within-day variability in the severe disorder of consciousness. Journal of Neurotrauma, 28(10), 2013–2017. https://doi.org/10.1089/neu.2011.1885.
10.
CasseG.SauvageJ. P.AdenisJ. P.RobertP. Y. (2007). Videonystagmography to assess blinking. Graefe’s Archive for Clinical and Experimental Ophthalmology, 245(12), 1789–1796. https://doi.org/10.1007/s00417-007-0611-8.
11.
ChatelleC.MajerusS.WhyteJ.LaureysS.SchnakersC. (2012). A sensitive scale to assess nociceptive pain in patients with disorders of consciousness. Journal of Neurology, Neurosurgery, and Psychiatry, 83(12), 1233–1237. https://doi.org/10.1136/jnnp-2012-302987.
12.
CorteseM. D.RiganelloF.ArcuriF.PuglieseM. E.LuccaL. F.DolceG.SannitaW. G. (2015). Coma recovery scale-r: Variability in the disorder of consciousness. BMC Neurology, 15, 186. https://doi.org/10.1186/s12883-015-0455-5.
13.
DerchiC. C.MikulanE.MazzaA.CasarottoS.ComanducciA.FecchioM.NavarroJ.DevalleG.MassiminiM.SinigagliaC. (2023). Distinguishing intentional from nonintentional actions through eeg and kinematic markers. Scientific Reports, 13(1), 8496. https://doi.org/10.1038/s41598-023-34604-y.
14.
EstraneoA.FiorenzaS.MagliacanoA.FormisanoR.MattiaD.GrippoA.RomoliA. M.AngelakisE.CassolH.ThibautA.GosseriesO.LambertiG.NoéE.BagnatoS.EdlowB. L.ChatelleC.LejeuneN.VeeramuthuV.BartoloM.ToppiJ., . . . … IBIA DoC-SIG. (2020). Multicenter prospective study on predictors of short-term outcome in disorders of consciousness. Neurology, 95(11), e1488–e1499. https://doi.org/10.1212/WNL.0000000000010254.
15.
EstraneoA.LoretoV.GuarinoI.BoemiaV.PaoneG.MorettaP.TrojanoL. (2016). Standard EEG in diagnostic process of prolonged disorders of consciousness. Clinical Neurophysiology, 127(6), 2379–2385. https://doi.org/10.1016/j.clinph.2016.03.021.
16.
EstraneoA.MasottaO.BartoloM.PistoiaF.PerinC.MarinoS.LuccaL.PingueV.CasanovaE.RomoliA.GentileS.FormisanoR.SalviG. P.ScarponiF.De TantiA.BongioanniP.RossatoE.SantangeloA.DianaA. R.GambarinM.De BellisF. (2021). Multi-center study on overall clinical complexity of patients with prolonged disorders of consciousness of different etiologies. Brain Injury, 35(1), 1–7. https://doi.org/10.1080/02699052.2020.1861652.
17.
EstraneoA.PascarellaA.MorettaP.MasottaO.FiorenzaS.ChiricoG.CrispinoE.LoretoV.TrojanoL. (2017). Repeated transcranial direct current stimulation in prolonged disorders of consciousness: A double-blind cross-over study. Journal of the Neurological Sciences, 375, 464–470. https://doi.org/10.1016/j.jns.2017.02.036.
18.
EstraneoA.TrojanoL. (2018). Prognosis in disorders of consciousness. In Coma and disorders of consciousness, 2nd ed.; SchnakersC., & LaureysS., Eds.; Springer Cham, pp. 17–36.
19.
ForgacsP. B.AllenB. B.WuX.GerberL. M.BodduS.FakharM.StiegP. E.SchiffN. D.MangatH. S. (2022). Corticothalamic connectivity in aneurysmal subarachnoid hemorrhage: Relationship with disordered consciousness and clinical outcomes. Neurocritical Care, 36(3), 760–771. https://doi.org/10.1007/s12028-021-01354-6.
20.
ForgacsP. B.FreyH. P.VelazquezA.ThompsonS.BrodieD.MoitraV.RabaniL.ParkS.AgarwalS.FaloM. C.SchiffN. D.ClaassenJ. (2017). Dynamic regimes of neocortical activity linked to corticothalamic integrity correlate with outcomes in acute anoxic brain injury after cardiac arrest. Annals of Clinical and Translational Neurology, 4(2), 119–129. https://doi.org/10.1002/acn3.385.
21.
FrohlichJ.CroneJ. S.JohnsonM. A.LutkenhoffE. S.SpivakN. M.Dell’ItaliaJ.HippJ. F.ShresthaV.Ruiz TejedaJ. E.RealC.VespaP. M.MontiM. M. (2022). Neural oscillations track recovery of consciousness in acute traumatic brain injury patients. Human Brain Mapping, 43(6), 1804–1820. https://doi.org/10.1002/hbm.25725.
22.
GaoQ.HaoJ.KangX.YuanF.LiuY.ChenR.LiuX.LiR.JiangW. (2023). EEG dynamics induced by zolpidem forecast consciousness evolution in prolonged disorders of consciousness. Clinical Neurophysiology, 153, 46–56. https://doi.org/10.1016/j.clinph.2023.06.012.
23.
GiacinoJ. T.AshwalS.ChildsN.CranfordR.JennettB.KatzD. I.KellyJ. P.RosenbergJ. H.WhyteJ.ZafonteR. D.ZaslerN. D. (2002). The minimally conscious state: Definition and diagnostic criteria. Neurology, 349–353. https://doi.org/10.1212/wnl.58.3.349.
24.
GiacinoJ. T.KatzD. I.SchiffN. D.WhyteJ.AshmanE. J.AshwalS.BarbanoR.HammondF. M.LaureysS.LingG. S. F.Nakase-RichardsonR.SeelR. T.YablonS.GetchiusT. S. D.GronsethG. S.ArmstrongM. J. (2018). Practice guideline update recommendations summary: Disorders of consciousness: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology; the American Congress of Rehabilitation Medicine; and the National Institute on Disability, Independent Living, and Rehabilitation Research. Neurology, 91(10), 450–460. https://doi.org/10.1212/WNL.0000000000005926.
25.
KaminerJ.PowersA. S.HornK. G.HuiC.EvingerC. (2011). Characterizing the spontaneous blink generator: An animal model. The Journal of Neuroscience, 31(31), 11256–11267. https://doi.org/10.1523/JNEUROSCI.6218-10.2011.
26.
KapitaniakB.WalczakM.KosobudzkiM.JóźwiakZ.BortkiewiczA. (2015). Application of eye-tracking in the testing of drivers: A review of research. International Journal of Occupational Medicine and Environmental Health, 28(6), 941–954. https://doi.org/10.13075/ijomeh.1896.00317.
27.
KondziellaD.BenderA.DiserensK.van ErpW.EstraneoA.FormisanoR.LaureysS.NaccacheL.OzturkS.RohautB.SittJ. D.StenderJ.TiainenM.RossettiA. O.GosseriesO.ChatelleC., EAN Panel on Coma, Disorders of Consciousness. (2020). European Academy of Neurology guideline on the diagnosis of coma and other disorders of consciousness. European Journal of Neurology, 27(5), 741–756. https://doi.org/10.1111/ene.14151.
28.
LaureysS.CelesiaG. G.CohadonF.LavrijsenJ.León-CarriónJ.SannitaW. G.SazbonL.SchmutzhardE.von WildK. R.ZemanA.DolceG., European Task Force on Disorders of Consciousness. (2010). Unresponsive wakefulness syndrome: A new name for the vegetative state or apallic syndrome. BMC Medicine, 8, 68. https://doi.org/10.1186/1741-7015-8-68.
29.
MagliacanoA.CatalanoL.SaglianoL.EstraneoA.TrojanoL. (2023). Spontaneous eye blinking during an auditory, an interoceptive and a visual task: The role of the sensory modality and the attentional focus. Cortex, 168, 49–61. https://doi.org/10.1016/j.cortex.2023.07.006.
30.
MagliacanoA.FiorenzaS.EstraneoA.TrojanoL. (2020). Eye blink rate increases as a function of cognitive load during an auditory oddball paradigm. Neuroscience Letters, 736, 135293. https://doi.org/10.1016/j.neulet.2020.135293.
31.
MagliacanoA.RosenfelderM.HieberN.BenderA.EstraneoA.TrojanoL. (2021). Spontaneous eye blinking as a diagnostic marker in prolonged disorders of consciousness. Scientific Reports, 11(1), 22393. https://doi.org/10.1038/s41598-021-01858-3.
32.
NakanoT. (2017). The right angular gyrus controls spontaneous eyeblink rate: A combined structural MRI and TMS study. Cortex, 88, 186–191. https://doi.org/10.1016/j.cortex.2016.12.022.
33.
NaroA.ChilluraA.PortaroS.BramantiA.De LucaR.BramantiP.CalabròR. S. (2018). Novel approaches to the diagnosis of chronic disorders of consciousness: Detecting peripersonal space by using ultrasonics. Frontiers in Neurology, 9, 47. https://doi.org/10.3389/fneur.2018.00047.
34.
PincherleA.RossiF.JöhrJ.DunetV.RyvlinP.OddoM.SchiffN.DiserensK. (2021). Early discrimination of cognitive motor dissociation from disorders of consciousness: Pitfalls and clues. Journal of Neurology, 268(1), 178–188. https://doi.org/10.1007/s00415-020-10125-w.
35.
SattinD.MinatiL.RossiD.CovelliV.GiovannettiA. M.RosazzaC.BersanoA.NigriA.LeonardiM. (2015). The Coma Recovery Scale Modified Score: A new scoring system for the Coma Recovery Scale-revised for assessment of patients with disorders of consciousness. International Journal of Rehabilitation Research, 38(4), 350–356. https://doi.org/10.1097/MRR.0000000000000135.
36.
SattinD.MorgantiL.De TorresL.DolceG.ArcuriF.EstraneoA.CardinaleV.PipernoR.ZavattaE.FormisanoR.D’IppolitoM.VassalloC.DessiB.LambertiG.AntonionoE.LanzillottiC.NavarroJ.BramantiP.CoralloF.ZampoliniM.LeonardiM. (2017). Care pathways models and clinical outcomes in Disorders of consciousness. Brain and Behavior, 7(8), e00740. https://doi.org/10.1002/brb3.740.
37.
SchiffN. D. (2010). Recovery of consciousness after brain injury: A mesocircuit hypothesis. Trends in Neurosciences, 33(1), 1–9. https://doi.org/10.1016/j.tins.2009.11.002.
38.
SchnakersC.HirschM.NoéE.LlorensR.LejeuneN.VeeramuthuV.De MarcoS.DemertziA.DuclosC.MorrisseyA. M.ChatelleC.EstraneoA. (2020). Covert cognition in disorders of consciousness: A meta-analysis. Brain Sciences, 10(12), 930. https://doi.org/10.3390/brainsci10120930.
39.
Talens-EstarellesC.Esteve-TaboadaJ. J.Sanchis-JuradoV.PonsÁ. M.García-LázaroS. (2022). Blinking kinematics characterization during digital displays use. Graefe’s Archive for Clinical and Experimental Ophthalmology, 260(4), 1183–1193. https://doi.org/10.1007/s00417-021-05490-9.
WislowskaM.Del GiudiceR.LechingerJ.WielekT.HeibD. P. J.PitiotA.PichlerG.MichitschG.DonisJ.SchabusM. (2017). Night and day variations of sleep in patients with disorders of consciousness. Scientific Reports, 7(1), 266. https://doi.org/10.1038/s41598-017-00323-4.
