Evolution of severe sleep-wake cycle disturbances following traumatic brain injury: a case study in both acute and subacute phases post-injury

Abstract Background Sleep-wake disturbances are frequently reported following traumatic brain injury (TBI), but they remain poorly documented in the acute stage of injury. Little is known about their origin and evolution. Case presentation This study presents the case of a patient in the acute phase of a severe TBI. The patient was injured at work when falling 12 m into a mine and was hospitalized in the regular wards of a level I trauma centre. From days 31 to 45 post-injury, once he had reached a level of medical stability and continuous analgosedation had been ceased, his sleep-wake cycle was monitored using actigraphy. Results showed significant sleep-wake disturbances and severe sleep deprivation. Indeed, the patient had an average nighttime sleep efficiency of 32.7 ± 15.4 %, and only an average of 4.8 ± 1.3 h of sleep per 24-h period. After hospital discharge to the rehabilitation centre, where he remained for 5 days, the patient was readmitted to the same neurological unit for paranoid delusions. During his second hospital stay, actigraphy recordings resumed from days 69 to 75 post-injury. A major improvement in his sleep-wake cycle was observed during this second stay, with an average nighttime sleep efficiency of 96.3 ± 0.9 % and an average of 14.1 ± 0.9 h of sleep per 24-h period. Conclusion This study is the first to extensively document sleep-wake disturbances in both the acute and subacute phases of severe TBI. Results show that prolonged sleep deprivation can be observed after TBI, and suggest that the hospital environment only partially contributes to sleep-wake disturbances. Continuous actigraphic monitoring may prove to be a useful clinical tool in the monitoring of patients hospitalized after severe TBI in order to detect severe sleep deprivation requiring intervention. The direct impact of sleep-wake disturbances on physiological and cognitive recovery is not well understood within this population, but is worth investigating and improving

A longitudinal study of narrative discourse in post-stroke aphasia

Background: Previous findings have demonstrated the importance of discourse analysis in post-stroke aphasia, as it allows for in-depth examination of language impairment and represents key components of functional communication. However, little is known about the recovery of discourse over time. Aims: The main aim of this study is to measure the longitudinal changes in descriptive discourse production from the acute to chronic stages of post-stroke aphasia recovery. The secondary aim is to explore the association between discourse measures and overall language impairment severity measures at different testing points. Methods & Procedure: Seventeen French Canadian speakers with various types and severities of aphasia following a first left middle cerebral artery stroke participated in this study. They underwent three language assessments (acute: 0 to 72 hours; subacute: 7 to 14 days; chronic: 6 to 12 months post-onset). The picture description from the Western Aphasia Battery was analyzed at three time points. Changes in terms of thematic informativeness and microstructural variables were analyzed. Outcomes & Results: Regarding the micro-structural variables, the mean length of utterances (MLU) and the number of words per minute showed significant positive changes between the acute and chronic phases. For the thematic informativeness measures, the number of thematic units (TUs), the number of thematic units per minute (TUs/min) and the number of thematic units per utterance (TUs/utt) 4 increased significantly between the acute and chronic phases. Positive correlations between TUs and MLU in the acute phase and a general language impairment severity measure in the acute and chronic phases suggest a relationship between these measures and global language performance suggesting the potential predictive value of these variables in the acute phase. Conclusions & Implications: These findings support the use of thematic units in descriptive discourse analysis during an acute clinical examination of language as they require minimal additional time to score and track changes in post-stroke aphasia recovery. They capture long-term changes in discourse abilities and appear related to overall language measures in both the acute and chronic stages of recovery. The interpretation of the changes in MLU and the number of words per minute is less straightforward, as improvements in these measures carry different interpretations depending on the type of aphasia. Nonetheless, further studies are required to investigate test-retest reliability and the effect of therapy on the changes observed over time when using thematic units to document change in discourse

Evolution of severe sleep-wake cycle disturbances following traumatic brain injury: a case study in both acute and subacute phases post-injury.

BACKGROUND: Sleep-wake disturbances are frequently reported following traumatic brain injury (TBI), but they remain poorly documented in the acute stage of injury. Little is known about their origin and evolution. CASE PRESENTATION: This study presents the case of a patient in the acute phase of a severe TBI. The patient was injured at work when falling 12 m into a mine and was hospitalized in the regular wards of a level I trauma centre. From days 31 to 45 post-injury, once he had reached a level of medical stability and continuous analgosedation had been ceased, his sleep-wake cycle was monitored using actigraphy. Results showed significant sleep-wake disturbances and severe sleep deprivation. Indeed, the patient had an average nighttime sleep efficiency of 32.7 ± 15.4 %, and only an average of 4.8 ± 1.3 h of sleep per 24-h period. After hospital discharge to the rehabilitation centre, where he remained for 5 days, the patient was readmitted to the same neurological unit for paranoid delusions. During his second hospital stay, actigraphy recordings resumed from days 69 to 75 post-injury. A major improvement in his sleep-wake cycle was observed during this second stay, with an average nighttime sleep efficiency of 96.3 ± 0.9 % and an average of 14.1 ± 0.9 h of sleep per 24-h period. CONCLUSION: This study is the first to extensively document sleep-wake disturbances in both the acute and subacute phases of severe TBI. Results show that prolonged sleep deprivation can be observed after TBI, and suggest that the hospital environment only partially contributes to sleep-wake disturbances. Continuous actigraphic monitoring may prove to be a useful clinical tool in the monitoring of patients hospitalized after severe TBI in order to detect severe sleep deprivation requiring intervention. The direct impact of sleep-wake disturbances on physiological and cognitive recovery is not well understood within this population, but is worth investigating and improving

The importance of thematic informativeness in narrative discourse recovery in acute post-stroke aphasia

Background: Discourse analysis allows the examination of functional and ecological language impairment in post-stroke aphasia. Given its complexity, various methods of analysis have been developed to measure the multiple components of discourse. Clinical assessment usually includes discourse analysis, but how clinicians should assess recovery of discourse, particularly in acute care settings, is still a matter of debate. Aims: This study aimed to measure improvements in discourse production in early post-stroke aphasia recovery. Methods & Procedure: Twenty-three persons with aphasia following a first left middle cerebral artery stroke were recruited in the stroke unit of Hôpital du Sacré-Coeur de Montréal (May 2015-July 2018). Patients treated with thrombolysis (n = 10) and untreated patients underwent two aphasia assessments (0 to 72 hours, 7 to 14 days post-onset). Discourse assessment consisted of the picture description task from the Western Aphasia Battery. Changes in microlinguistic and thematic informativeness measures between the two assessment periods were analyzed. Outcomes & Results: In-depth microlinguistic analyses showed no significant difference between the initial and follow-up assessments. Conversely, some thematic informativeness variables improved significantly during the same time period. Patients treated with thrombolysis produced more thematic units than untreated patients at both assessments, but the change between the two groups was not significant. Conclusions & Implications: This study suggests that thematic informativeness variables are sensitive to language improvement in early post-stroke aphasia recovery whereas no microlinguistic variables improved significantly in the same period. In contrast to previous evidence, the difference between patients treated with thrombolysis and untreated patients was not evident over time. The results suggest that thematic informativeness constitutes an interesting path to explore as a routine clinical assessment in acute-care settings because it is time-efficient, simple to conduct and reliable in assessing early changes in the discourse production of individuals with aphasia in the acute post-stroke phase

Sleep and wake disturbances following traumatic brain injury

Traumatic brain injury (TBI) is a major health concern in industrialised countries. Sleep and wake disturbances are among the most persistent and disabling sequelae after TBI. Yet, despite the widespread complaints of post-TBI sleep and wake disturbances, studies on their etiology, pathophysiology, and treatments remain inconclusive. This narrative review aims to summarise the current state of knowledge regarding the nature of sleep and wake disturbances following TBI, both subjective and objective, spanning all levels of severity and phases postinjury. A second goal is to outline the various causes of post-TBI sleep-wake disturbances. Globally, although sleep-wake complaints are reported in all studies and across all levels of severity, consensus regarding the objective nature of these disturbances is not unanimous and varies widely across studies. In order to optimize recovery in TBI survivors, further studies are required to shed light on the complexity and heterogeneity of post-TBI sleep and wake disturbances, and to fully grasp the best timing and approach for intervention

Predicting early post-stroke aphasia outcome from initial aphasia severity

Background: The greatest degree of language recovery in post-stroke aphasia takes place within the first weeks. Aphasia severity and lesion measures have been shown to be good predictors of long-term outcomes. However, little is known about their implications in early spontaneous recovery. The present study sought to determine which factors better predict early language outcomes in individuals with post-stroke aphasia. Methods: Twenty individuals with post-stroke aphasia were assessed <72 h (acute) and 10–14 days (subacute) after stroke onset. We developed a composite score (CS) consisting of several linguistic sub-tests: repetition, oral comprehension and naming. Lesion volume, lesion load and diffusion measures [fractional anisotropy (FA) and axial diffusivity (AD)] from both arcuate fasciculi (AF) were also extracted using MRI scans performed at the same time points. A series of regression analyses were performed to predict the CS at the second assessment. Results: Among the diffusion measures, only FA from right AF was found to be a significant predictor of early subacute aphasia outcome. However, when combined in two hierarchical models with FA, age and either lesion load or lesion size, the initial aphasia severity was found to account for most of the variance (R 2 = 0.678), similarly to the complete models (R 2 = 0.703 and R 2 = 0.73, respectively). Conclusions: Initial aphasia severity was the best predictor of early post-stroke aphasia outcome, whereas lesion measures, though highly correlated, show less influence on the prediction model. We suggest that factors predicting early recovery may differ from those involved in long-term recovery

Test-retest reliability of diffusion measures extracted along white matter language fiber bundles using HARDI-based tractography

High angular resolution diffusion imaging (HARDI)-based tractography has been increasingly used in longitudinal studies on white matter macro- and micro-structural changes in the language network during language acquisition and in language impairments. However, test-retest reliability measurements are essential to ascertain that the longitudinal variations observed are not related to data processing. The aims of this study were to determine the reproducibility of the reconstruction of major white matter fiber bundles of the language network using anatomically constrained probabilistic tractography with constrained spherical deconvolution based on HARDI data, as well as to assess the test-retest reliability of diffusion measures extracted along them. Eighteen right-handed participants were scanned twice, one week apart. The arcuate, inferior longitudinal, inferior fronto-occipital, and uncinate fasciculi were reconstructed in the left and right hemispheres and the following diffusion measures were extracted along each tract: fractional anisotropy, mean, axial, and radial diffusivity, number of fiber orientations, mean length of streamlines, and volume. All fiber bundles showed good morphological overlap between the two scanning timepoints and the test-retest reliability of all diffusion measures in most fiber bundles was good to excellent. We thus propose a fairly simple, but robust, HARDI-based tractography pipeline reliable for the longitudinal study of white matter language fiber bundles, which increases its potential applicability to research on the neurobiological mechanisms supporting language

Test-Retest Reliability of Diffusion Measures Extracted Along White Matter Language Fiber Bundles Using HARDI-Based Tractography

High angular resolution diffusion imaging (HARDI)-based tractography has been increasingly used in longitudinal studies on white matter macro- and micro-structural changes in the language network during language acquisition and in language impairments. However, test-retest reliability measurements are essential to ascertain that the longitudinal variations observed are not related to data processing. The aims of this study were to determine the reproducibility of the reconstruction of major white matter fiber bundles of the language network using anatomically constrained probabilistic tractography with constrained spherical deconvolution based on HARDI data, as well as to assess the test-retest reliability of diffusion measures extracted along them. Eighteen right-handed participants were scanned twice, one week apart. The arcuate, inferior longitudinal, inferior fronto-occipital, and uncinate fasciculi were reconstructed in the left and right hemispheres and the following diffusion measures were extracted along each tract: fractional anisotropy, mean, axial, and radial diffusivity, number of fiber orientations, mean length of streamlines, and volume. All fiber bundles showed good morphological overlap between the two scanning timepoints and the test-retest reliability of all diffusion measures in most fiber bundles was good to excellent. We thus propose a fairly simple, but robust, HARDI-based tractography pipeline reliable for the longitudinal study of white matter language fiber bundles, which increases its potential applicability to research on the neurobiological mechanisms supporting language

Visual fixation in the intensive care unit: a strong predictor of post-traumatic amnesia and long-term recovery after moderate-to-severe traumatic brain injury

Objective: We examined whether visual fixation at 24h of intensive care unit (ICU) admission is superior to the initial Glasgow Coma Scale (GCS) score to predict PTA duration and long-term TBI recovery. Design: Two-phase cohort study. Setting: Level I trauma ICU. Patients: Moderate-to-severe TBI discharged alive between 2010-2013. Interventions: None. Measurements and Main Results: Presence/absence of visual fixation at 24h of ICU-admission was determined through standard behavioral assessments in 181 TBI patients and compared to the GCS score to predict PTA duration during hospitalization (Phase 1) and performance on the Glasgow Outcome Scale-Extended (GOS-E) 10-40 months after (n=144; Phase 2a). A subgroup also completed a visual attention task (n=35; Phase 2b) and brain magnetic resonance imaging post-TBI (n=23; Phase 2c). Presence/absence of visual fixation at 24h of ICU-admission showed a sensitivity of 84%, a specificity of 82% and an AUC of 0.87 for the prediction of PTA duration. Visual fixation (AUC=0.85) was also found as performant as PTA (AUC=0.81; difference-between-AUC=0.04; 95%CI:-0.03-0.116; p=0.28) for the prediction of GOS-E scores. Conversely, the GCS score was a poor predictor of both PTA and GOS-E. Even when controlling for age/medication/CT scan findings, fixation remained a significant predictor of GOS-E scores (=-0.29, p<0.05). Poorer attention performance and increased regional brain volume deficits were also observed in participants who could not fixate 24h following ICU-admission versus those who could. Conclusions: Visual fixation within 24h of ICU-admission could be as performant as PTA for predicting TBI recovery, introducing a new variable of interest in TBI outcome research

Analysis of common and rare VPS13C variants in late-onset Parkinson disease

Objective We aimed to study the role of coding VPS13C variants in a large cohort of patients with lateonset Parkinson disease (PD) (LOPD). Methods VPS13C and its untranslated regions were sequenced using targeted next-generation sequencing in 1,567 patients with PD and 1,667 controls from 3 cohorts. Association tests of rare potential homozygous and compound heterozygous variants and burden tests for rare heterozygous variants were performed. Common variants were analyzed using logistic regression adjusted for age and sex in each of the cohorts, followed by a meta-analysis. Results No biallelic carriers of rare VPS13C variants were found among patients, and 2 carriers of compound heterozygous variants were found in 2 controls. There was no statistically significant burden of rare (minor allele frequency [MAF] <1%) or very rare (MAF <0.1%) coding VPS13C variants in PD. A VPS13C haplotype including the p.R153H-p.I398I-p.I1132V-p.Q2376Q variants was nominally associated with a reduced risk for PD (meta-analysis of the tagging SNP p.I1132V [odds ratio = 0.48, 95% confidence interval = 0.28–0.82, p = 0.0052]). This haplotype was not in linkage disequilibrium with the known genome-wide association study top hit. Conclusions Our results do not support a role for rare heterozygous or biallelic VPS13C variants in LOPD. Additional genetic replication and functional studies are needed to examine the role of the haplotype identified here associated with reduced risk for PD