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Sustained Axonal Degeneration in Prolonged Disorders of Consciousness.

ABSTRACT: (1) Background: Sustained axonal degeneration may play a critical role in prolonged disorder of consciousness (DOCs) pathophysiology. We evaluated levels of neurofilament light chain (NFL), an axonal injury marker, in patients with unresponsive wakefulness syndrome (UWS) and in the minimally conscious state (MCS) after traumatic brain injury (TBI) and hypoxic-ischemic brain injury (HIBI). (2) Methods: This prospective multicenter blinded study involved 70 patients with prolonged DOC and 70 sex-/age-matched healthy controls. Serum NFL levels were evaluated at 1-3 and 6 months post-injury and compared with those of controls. NFL levels were compared by DOC severity (UWS vs. MCS) and etiology (TBI vs. HIBI). (3) Results: Patients' serum NFL levels were significantly higher than those of controls at 1-3 and 6 months post-injury (medians, 1729 and 426 vs. 90 pg/mL; both p < 0.0001). NFL levels were higher in patients with UWS than in those in MCS at 1-3 months post-injury (p = 0.008) and in patients with HIBI than in those with TBI at 6 months post-injury (p = 0.037). (4) Conclusions: Patients with prolonged DOC present sustained axonal degeneration that is affected differently over time by brain injury severity and etiology.

SUBMITTER: Bagnato S

PROVIDER: S-EPMC8394581 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Sustained Axonal Degeneration in Prolonged Disorders of Consciousness.

Bagnato Sergio S D'Ippolito Maria Enza ME Boccagni Cristina C De Tanti Antonio A Lucca Lucia Francesca LF Nardone Antonio A Salucci Pamela P Fiorilla Teresa T Pingue Valeria V Gennaro Serena S Ursino Maria M Colombo Valentina V Barone Teresa T Rubino Francesca F Andriolo Maria M

Brain sciences 20210814 8

(1) Background: Sustained axonal degeneration may play a critical role in prolonged disorder of consciousness (DOCs) pathophysiology. We evaluated levels of neurofilament light chain (NFL), an axonal injury marker, in patients with unresponsive wakefulness syndrome (UWS) and in the minimally conscious state (MCS) after traumatic brain injury (TBI) and hypoxic-ischemic brain injury (HIBI). (2) Methods: This prospective multicenter blinded study involved 70 patients with prolonged DOC and 70 sex-/ ...[more]

PMID: 34439687

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Project description:BackgroundApomorphine is a dopaminergic candidate therapy to improve recovery in patients with prolonged disorders of consciousness (PDoC). Behavioural improvements were previously described in non-controlled case series, but its efficacy and neural mechanisms remain largely unknown. This open-label controlled study using multimodal outcome measures investigates the action of apomorphine in severely brain-injured patients.MethodsThirteen PDoC patients received 30-day subcutaneous apomorphine treatment (n = 6) or standard care (control group, n = 7) in a neurological rehabilitation centre between February 2018 and January 2021. The apomorphine group was monitored 30 days before treatment initiation, during treatment and one year after treatment. Primary outcome measure was defined as changes in behavioural diagnosis using the Coma Recovery Scale-Revised (CRS-R). CRS-R index, recovery of new conscious behaviours, DoC-feeling scores, high-density electroencephalography, and fluorodeoxyglucose positron emission tomography were employed as secondary outcome measures. The control group was monitored with repeated CRS-R only. Registration: EudraCT 2018-003144-23; Clinicaltrials.govNCT03623828.FindingsGroups (apomorphine vs. control: odds ratio 8.9, 95% CI 3.3-17.8) and study phase (treatment vs. baseline, apomorphine group only: odds ratio 3.9, 95% CI 1.5-10.1) significantly influenced positive changes in behavioural diagnosis. At one-year post-injury, 4/6 patients in the apomorphine group and 1/7 patients in the control group had improved their diagnosis. Similarly, CRS-R index was significantly influenced by study phase (treatment vs. baseline). All items on the DoC-feeling score were rated higher after treatment than before by both family and medical staff. Patients in the apomorphine group recovered more conscious behaviours than control patients. Alpha-band whole-brain connectivity and participation coefficient, as well as alpha-band parieto-temporal connectivity and frontal participation coefficient were higher after treatment than at baseline. Whole-brain metabolism increased by a relative mean of 13.8% after treatment compared to baseline, with a significant effect of timing (pre-vs. post-treatment scans) on regional SUV.InterpretationLong-lasting consciousness improvements were observed in patients treated with apomorphine, compared to controls and compared to baseline. Changes in brain connectivity and metabolism were observed after treatment, providing insights into possible neurophysiological mechanisms and target areas. This open-label study confirmed the feasibility and safety of apomorphine treatment, which may represent a key therapeutic option for PDoC.FundingUniversity and University Hospital of Liege, Belgian National Funds for Scientific Research, Fund Generet of the King Baudouin Foundation, AstraZeneca Foundation, Leon Fredericq Foundation and NeuroHealing Pharmaceuticals Inc.

Project description:ObjectiveThis study aimed to explore differences in sleep electroencephalogram (EEG) patterns in individuals with prolonged disorders of consciousness, utilizing polysomnography (PSG) to assist in distinguishing between the vegetative state (VS)/unresponsive wakefulness syndrome (UWS) and the minimally conscious state (MCS), thereby reducing misdiagnosis rates and enhancing the quality of medical treatment.MethodsA total of 40 patients with prolonged disorders of consciousness (pDOC; 27 patients in the VS/UWS and 13 in the MCS) underwent polysomnography. We analyzed differential EEG indices between VS/UWS and MCS groups and performed correlation analyses between these indices and the Coma Recovery Scale-Revised (CRS-R) scores. The diagnostic accuracy of the differential indices was evaluated using receiver operating characteristic (ROC) curves.Results1. The fractal dimension (Higuchi's fractal dimension (HFD)) of patients in the MCS tended to be higher than that of patients in the VS/UWS across all phases, with a significant difference only in the waking phase (p < 0.05). The HFD in the waking phase was positively correlated with the CRS-R score and exhibited the highest diagnostic accuracy at 88.3%. The Teager-Kaiser energy operator (TKEO) also showed higher levels in patients in the MCS compared to those in the VS/UWS, significantly so in the NREM2 phase (p < 0.05), with a positive correlation with the CRS-R score and diagnostic accuracy of 75.2%. The δ-band power spectral density [PSD(δ)] in the patients in the MCS was lower than that in those in the VS/UWS, significantly so in the waking phase (p < 0.05), and it was negatively correlated with the CRS-R score, with diagnostic accuracy of 71.5%.ConclusionPolysomnography for the VS/UWS and MCS revealed significant differences, aiding in distinguishing between the two patient categories and reducing misdiagnosis rates. Notably, the HFD and PSD(δ) showed significantly better performance during wakefulness compared to sleep, while the TKEO was more prominent in the NREM2 stage. Notably, the HFD exhibited a robust correlation with the CRS-R scores, the highest diagnostic accuracy, and immense promise in the clinical diagnosis of prolonged disorders of consciousness.

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Sustained Axonal Degeneration in Prolonged Disorders of Consciousness.

Publications

Sustained Axonal Degeneration in Prolonged Disorders of Consciousness.

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