Significance of circadian rhythms in severely brain-injured patients

Blume, Christine; Lechinger, Julia; Santhi, Nayantara; Giudice, Renata Del; Gnjezda, Maria-Teresa; Pichler, Gerhard; Scarpatetti, Monika; Donis, Johann; Michitsch, Gabriele; Schabus, Manuel

doi:10.1212/wnl.0000000000003942

Cited by 60 publications

(66 citation statements)

References 39 publications

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“…Note that, although the effect was not overly strong, it may still be decisive for whether consciousness is attested or not. The findings are in line with speculations in an earlier study from our group and suggest that cognitive performance peaks around the time of the temperature maximum, i.e. around 4 pm in healthy individuals, median of the study sample 2:25 pm.…”

Section: Discussionsupporting

confidence: 92%

“…Amongst these, higher integrity of the melatonin rhythm and less deviation of the temperature rhythm from the supposedly ‘healthy’ period length of 24.18 h were related to higher CRS‐R scores. In line with earlier findings , this first of all provides further support for the notion of the significance of circadian rhythms in severely brain‐injured patients. More precisely, besides awareness, adequate arousal levels are seen as a necessary background condition for consciousness .…”

Section: Discussionsupporting

confidence: 91%

“…Indeed, this hypothesis is supported by recent research from our group, where it was shown that the integrity of a patient's circadian rhythm is related to the arousal/wakefulness scores on the Coma Recovery Scale – Revised (CRS‐R) . Previously, research on the significance of circadian rhythms for consciousness in brain‐injured patients has looked at circadian variations in temperature , cardiac parameters or hormones such as melatonin and their relation to patients’ consciousness states. However, these studies have only considered single circadian parameters rather than looking at several manifestations of circadian rhythms in conjunction.…”

Section: Theoretical Backgroundmentioning

confidence: 72%

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Healthier rhythm, healthier brain? Integrity of circadian melatonin and temperature rhythms relates to the clinical state of brain‐injured patients

Blume

Angerer

Raml

et al. 2019

Euro J of Neurology

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Background Healthy circadian rhythmicity has been suggested to relate to a better state of brain‐injured patients and to support the emergence of consciousness in patient groups characterized by a relative instability thereof such as patients with disorders of consciousness (DOC). Methods Going beyond earlier studies, a systems‐level perspective was adopted and, using multilevel modelling, the joint predictive value of three indices of circadian rhythm integrity derived from skin temperature variations, melatoninsulfate secretion, and physical activity (wrist actigraphy) patterns was evaluated for the behaviourally assessed state [Coma Recovery Scale ‐ Revised (CRS‐R) score] of DOC patients [13 unresponsive wakefulness syndrome; seven minimally conscious (exit) state]. Additionally, it was assessed in a subset of 16 patients whether patients’ behavioural repertoire (CRS‐R score) varied (i) with time of day or (ii) offset from the body temperature maximum (BTmax), i.e. when cognitive performance is expected to peak. Results The results reveal that better integrity of circadian melatoninsulfate and temperature rhythms relate to a richer behavioural repertoire. Moreover, higher CRS‐R scores are, by trend, related to assessments taking place at a later daytime or deviating less from the pre‐specified time of occurrence of BTmax. Conclusions In conclusion, the results suggest that therapeutic approaches aimed at improving circadian rhythms in brain‐injured patients are promising and should be implemented in hospitals or nursing homes. Beyond this, it might be helpful to schedule diagnostic procedures and therapies around the (pre‐assessed) BTmax (≈4 pm in healthy individuals) as this is when patients should be most responsive.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 91%

Section: Theoretical Backgroundmentioning

confidence: 72%

See 1 more Smart Citation

Healthier rhythm, healthier brain? Integrity of circadian melatonin and temperature rhythms relates to the clinical state of brain‐injured patients

Blume

Angerer

Raml

et al. 2019

Euro J of Neurology

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“…As consolidated periods of wakefulness and 30 sleep resulting from well-entrained circadian rhythms, seem crucial for adequate arousal 31 levels and thus (conscious) wakefulness, circadian rhythms have been the focus of recent 32 research in DOC patients. Research from our group 5,12 suggests that a better integrity of 33 patients' circadian melatonin(-sulfate) and temperature rhythms is indeed related to a richer 34 behavioral repertoire (as measured with the CRS-R). Knowing a patient's circadian rhythm in 35 turn has been suggested to help finding the optimal time for behavioral assessments and 36 therapies as cognitive functions also vary with the time of day [12][13][14] .…”

Section: Introductionmentioning

confidence: 99%

Actigraphy in brain-injured patients – A valid measurement for assessing circadian rhythms?

Angerer

Blume

Raml

et al. 2019

Preprint

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AbstractBackgroundActigraphy has received increasing attention in classifying rest-activity cycles. However, in patients with disorders of consciousness (DOC), actigraphy data may be considerably confounded by passive movements, such as nursing activities and therapies. Consequently, this study verified whether circadian rhythmicity is (still) visible in actigraphy data from patients with DOC after correcting for passive movements.MethodsWrist actigraphy was recorded over 7-8 consecutive days in patients with DOC (diagnosed with unresponsive wakefulness syndrome [UWS; n=19] and [exit] minimally conscious state [MCS/EMCS; n=11]). Presence and actions of clinical and research staff as well as visitors were indicated using a tablet in the patient’s room. Following removal and interpolation of passive movements, non-parametric rank-based tests were computed to identify differences between circadian parameters of uncorrected and corrected actigraphy data.ResultsUncorrected actigraphy data overestimated the interdaily stability and intradaily variability of patients’ activity and underestimated the deviation from a circadian 24h rhythm. Only 5/30 (17%) patients deviated more than 1h from 24h in the uncorrected data, whereas this was the case for 17/30 (57%) patients in the corrected data. When contrasting diagnoses based on the corrected dataset, stronger circadian rhythms and higher activity levels were observed in MCS/EMCS as compared to UWS patients. Day-to-night differences in activity were evident for both patient groups.ConclusionOur findings indicate that uncorrected actigraphy data overestimates the circadian rhythmicity of patients’ activity, as nursing activities, therapies, and visits by relatives follow a circadian pattern itself. Therefore, we suggest correcting actigraphy data from patients with reduced mobility.

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“…Body temperature rhythmicity was reported in VS and MCS patients, with a link between circadian period (closeness to 24 hours) and arousal. 15 Melatonin was reported to remain low at night during VS 16 ; however, the study was too short (a single night) to conclude on CR.…”

Section: Introductionmentioning

confidence: 94%

Is circadian rhythmicity a prerequisite to coma recovery? Circadian recovery concomitant to cognitive improvement in two comatose patients

Gobert

Luauté

Raverot

et al. 2019

Journal of Pineal Research

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Circadian rhythmicity (CR) is involved in the regulation of all integrated functions, from sleep‐wake cycle regulation to metabolic function, mood and cognition. However, the interdependence of CR, cognition and consciousness has been poorly addressed. To clarify the state of CR in coma and to determine the chronological relationship between its recovery and consciousness after brain lesions, we conducted a longitudinal observational study investigating how the state of CR was chronologically related with the recovery of behavioural wakefulness, cognition and/or awareness. Among 16 acute comatose patients, we recruited two 37‐year‐old patients with a persistent disorder of consciousness, presenting diencephalic lesions caused by severe traumatic brain injuries. Two biological urinary markers of CR were explored every 2 hours during 24 hours (6‐sulfatoxymelatonin, free cortisol) with a dedicated methodology to extract the endogenous component of rhythmicity (environmental light recording, near‐constant‐routine protocol, control of beta‐blockers). They presented an initial absence of rhythmic secretions and a recovered CR 7‐8 months later. This recovery was not associated with the restoration of behavioural wakefulness, but with an improvement of cognition and awareness (up to the minimally conscious state). MRI showed a lesion pattern compatible with the interruption of either the main hypothalamic‐sympathetic pathway or the accessory habenular pathway. These results suggest that CR may be a prerequisite for coma recovery with a potential but still unproven favourable effect on brain function of the resorted circadian melatonin secretion and/or the functional recovery of the suprachiasmatic nucleus (SCN). Assessing circadian functions by urinary melatonin should be further explored as a biomarker of cognition reappearance and investigated to prognosticate functional recovery.

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Significance of circadian rhythms in severely brain-injured patients

Cited by 60 publications

References 39 publications

Healthier rhythm, healthier brain? Integrity of circadian melatonin and temperature rhythms relates to the clinical state of brain‐injured patients

Healthier rhythm, healthier brain? Integrity of circadian melatonin and temperature rhythms relates to the clinical state of brain‐injured patients

Actigraphy in brain-injured patients – A valid measurement for assessing circadian rhythms?

Is circadian rhythmicity a prerequisite to coma recovery? Circadian recovery concomitant to cognitive improvement in two comatose patients

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