A neurophysiological profiling of the heartbeat-evoked potential in severe acquired brain injuries: A focus on unconsciousness.

Unconsciousness in severe acquired brain injury (sABI) patients occurs with different cognitive and neural profiles. Perturbational approaches, which enable the estimation of proxies for brain reorganization, have added a new avenue for investigating the non-behavioural diagnosis of consciousness. In this prospective observational study, we conducted a comparative analysis of the topological patterns of heartbeat-evoked potentials (HEP) between patients experiencing a prolonged disorder of consciousness (pDoC) and patients emerging from a minimally consciousness state (eMCS). A total of 219 sABI patients were enrolled, each undergoing a synchronous EEG-ECG resting-state recording, together with a standardized consciousness diagnosis. A number of graph metrics were computed before/after the HEP (Before/After) using the R-peak on the ECG signal. The peak value of the global field power of the HEP was found to be significantly higher in eMCS patients with no difference in latency. Power spectrum was not able to discriminate consciousness neither Before nor After. Node assortativity and global efficiency were found to vary with different trends at unconsciousness. Lastly, the Perturbational Complexity Index of the HEP was found to be significantly higher in eMCS patients compared with pDoC. Given that cortical elaboration of peripheral inputs may serve as a non-behavioural determinant of consciousness, we have devised a low-cost and translatable technique capable of estimating causal proxies of brain functionality with an endogenous, non-invasive stimulus. Thus, we present an effective means to enhance consciousness assessment by incorporating the interaction between the autonomic nervous system (ANS) and central nervous system (CNS) into the loop.

Depressive Symptoms Moderate the Association Between Functional Level at Admission to Intensive Post-Stroke Rehabilitation and Effectiveness of the Intervention.

INTRODUCTION: Previous studies showed that depression acts as an independent factor in functional recovery after stroke. In a prospective cohort of patients admitted to intensive inpatient rehabilitation after a stroke, we aimed to test depression as a moderator of the relationship between the functional level at admission and the effectiveness of rehabilitation at discharge. METHODS: All patients admitted to within 30 days from an ischemic or hemorrhagic stroke to 4 intensive rehabilitation units were prospectively screened for eligibility to a multicenter prospective observational study. Enrolled patients underwent an evidence-based rehabilitation pathway. We used clinical data collected at admission (T0) and discharge (T1). The outcome was the effectiveness of recovery at T1 on the modified Barthel Index (proportion of achieved over potential functional improvement). Moderation analysis was performed by using the PROCESS macro for SPSS using the bootstrapping procedure. RESULTS: Of 278 evaluated patients, 234 were eligible and consented to enrolment; 81 patients were able to answer to the Hospital Anxiety and Depression Scale (HADS) and were included in this analysis. The relationship between the functional status at admission and rehabilitation effectiveness was significant only in persons with fewer depressive symptoms; depression (HADS cut-off score: 5.9) moderated this relationship (P = .047), independent from age and neurological impairment. CONCLUSIONS: Our results suggest that depression moderates between the functional status at admission and the functional recovery after post-stroke rehabilitation. This approach facilitates the identification of subgroups of individuals who may respond differently to stroke rehabilitation based on depression.

Implications of the Consciousness State on Decannulation in Patients With a Prolonged Disorder of Consciousness.

OBJECTIVE: To prospectively investigate the evolution of the consciousness state and the cannula-weaning progression in patients with prolonged disorders of consciousness. DESIGN: Nonconcurrent cohort study. SETTING: A rehabilitation unit. PARTICIPANTS: Adult patients (N=144) with prolonged disorders of consciousness after a severe acquired brain injury admitted between June 2020 and September 2022. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Consciousness state was assessed by repeated Coma Recovery Scale-Revised (CRS-R) questionnaire administration at admission and weekly afterward. The dates of the first improvement of consciousness state and the achievement of decannulation were recorded. Decannulation followed an internal protocol of multiprofessional rehabilitation. RESULTS: One hundred forty-four patients were included: age, 69 years; 64 (44.4%) with hemorrhagic etiology; time post onset, 40 days, CRS-R score at admission, 9, median length of stay, 90 days. Seventy-three (50.7%) patients were decannulated. They showed a significantly higher CRS-R (P<.001) and states of consciousness (P<.001) at admission, at the first improvement of the consciousness state (P=.003), and at discharge (P<.001); a lower severity in the Cumulative Illness Rating Scale at admission (P=.01); and a lower rate of pulmonary infections with recurrence (P=.021), compared with nondecannulated patients. Almost all decannulated patients (97.3%) improved their consciousness before decannulation. Consciousness states at decannulation were as follows: unresponsive wakefulness syndrome, 0 (0%); minimally conscious state (MCS) minus, 4 (5.5%); MCS plus, 7 (9.6%); and emergence from MCS, 62 (84.9%). Kaplan-Meier analysis showed a significant divergence between the curves with a higher probability of decannulation in patients who improved consciousness (P<.001). CONCLUSIONS: This study showed that the presence of signs of consciousness, even subtle, is a necessary condition for decannulation, suggesting that consciousness may influence some of the components implied in the decannulation process.

Trunk Control Test as a Main Predictor of the Modified Barthel Index Score at Discharge From Intensive Post-acute Stroke Rehabilitation: Results From a Multicenter Italian Study.

OBJECTIVES: To verify whether trunk control test (TCT) upon admission to intensive inpatient post-stroke rehabilitation, combined with other confounding variables, is independently associated with discharge mBI. DESIGN: Multicentric retrospective observational cohort study. SETTING: Two Italian inpatient rehabilitation units. PARTICIPANTS: A total of 220 post-stroke adult patients, within 30 days from the acute event, were consecutively enrolled. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: The outcome measure considered was the modified Barthel Index (mBI), one of the most widely recommended tools for assessing stroke rehabilitation functional outcomes. RESULTS: All variables collected at admission and significantly associated with mBI at discharge in the univariate analysis (TCT, mBI at admission, pre-stroke modified Rankin Scale [mRS], sex, age, communication ability, time from the event, Cumulative Illness Rating Scale, bladder catheter, and pressure ulcers) entered the multivariate analysis. TCT, mBI at admission, premorbid disability (mRS), communication ability and pressure ulcers (P<.001) independently predicted discharge mBI (adjusted R2=68.5%). Concerning the role of TCT, the model with all covariates and without TCT presented an R2 of 65.1%. On the other side, the model with the TCT only presented an R2 of 53.1%. Finally, with the inclusion of both TCT and all covariates, the model showed an R2 increase up to 68.5%. CONCLUSIONS: TCT, with other features suggesting functional/clinical complexity, collected upon admission to post-acute intensive inpatient stroke rehabilitation, independently predicted discharge mBI.

Neural coding of autonomic functions in different states of consciousness.

Detecting signs of residual neural activity in patients with altered states of consciousness is a crucial issue for the customization of neurorehabilitation treatments and clinical decision-making. With this large observational prospective study, we propose an innovative approach to detect residual signs of consciousness via the assessment of the amount of autonomic information coded within the brain. The latter was estimated by computing the mutual information (MI) between preprocessed EEG and ECG signals, to be then compared across consciousness groups, together with the absolute power and an international qualitative labeling. One-hundred seventy-four patients (73 females, 42%) were included in the study (median age of 65 years [IQR = 20], MCS +: 29, MCS -: 23, UWS: 29). Electroencephalography (EEG) information content was found to be mostly related to the coding of electrocardiography (ECG) activity, i.e., with higher MI (p < 0.05), in Unresponsive Wakefulness Syndrome and Minimally Consciousness State minus (MCS -). EEG-ECG MI, besides clearly discriminating patients in an MCS - and +, significantly differed between lesioned areas (sides) in a subgroup of unilateral hemorrhagic patients. Crucially, such an accessible and non-invasive measure of residual consciousness signs was robust across electrodes and patient groups. Consequently, exiting from a strictly neuro-centric consciousness detection approach may be the key to provide complementary insights for the objective assessment of patients' consciousness levels and for the patient-specific planning of rehabilitative interventions.

Cognitive Profile in Patients Admitted to Intensive Rehabilitation after Stroke Is Associated with the Recovery of Dysphagia: Preliminary Results from the RIPS (Intensive Post-Stroke Rehabilitation) Study.

Dysphagia represents one of the most frequent symptoms in the post-acute stroke population. Swallowing impairment and cognitive deficits can often co-occur. This study aims to investigate the relationship between cognitive impairment and the recovery of dysphagia in patients attending specific rehabilitation. Patients admitted to intensive rehabilitation units were administered the Functional Oral Intake Scale (FOIS) and Montreal Cognitive Screening Test (MoCA); when screening positive for dysphagia, they entered a rehabilitation program. Their FOIS score at discharge was the primary outcome measure. In the multivariate analysis, younger age (B = - 0.077, p = 0.017), higher MoCA (B = 0.191, p = 0.002), and higher FOIS (B = 1.251, p = 0.032) at admission were associated with higher FOIS at discharge. When executive function (EF) replaced the MoCA total score in the model, younger age (B = - 0.134, p = 0.001), higher admission EF (B = 1.451, p < 0.001), and FOIS (B = 1.348, p = 0.035) were associated with higher FOIS at discharge. Our results confirm the hypothesis that a better cognitive profile upon admission is associated with a higher probability of dysphagia recovery at discharge. EF seems to have a crucial role in dysphagia recovery. These results highlight the importance of considering the cognitive profile when assessing and treating dysphagia after stroke and of using screening tests that include executive functions.

Effects of COVID-19 pandemic on intensive rehabilitation after severe acquired brain injuries.

PURPOSE: COVID-19 pandemic has affected most components of health systems including rehabilitation. The study aims to compare demographic and clinical data of patients admitted to an intensive rehabilitation unit (IRU) after severe acquired brain injuries (sABIs), before and during the pandemic. MATERIALS AND METHODS: In this observational retrospective study, all patients admitted to the IRU between 2017 and 2020 were included. Demographics were collected, as well as data from the clinical and functional assessment at admission and discharge from the IRU. Patients were grouped in years starting from March 2017, and the 2020/21 cohort was compared to those admitted between March 2017/18, 2018/19, and 2019/20. Lastly, the pooled cohort March 2017 to March 2020 was compared with the COVID-19 year alone. RESULTS: This study included 251 patients (F: 96 (38%): median age 68 years [IQR = 19.25], median time post-onset at admission: 42 days, [IQR = 23]). In comparison with the pre-pandemic years, a significant increase of hemorrhagic strokes (p < 0.001) and a decrease of traumatic brain injuries (p = 0.048), a reduction of the number of patients with a prolonged disorder of consciousness admitted to the IRU (p < 0.001) and a lower length of stay (p < 0.001) were observed in 2020/21. CONCLUSIONS: These differences in the case mix of sABI patients admitted to IRU may be considered another side-effect of the pandemic. Facing this health emergency, rehabilitation specialists need to adapt readily to the changing clinical and functional needs of patients' addressing the IRUs.

Decannulation and improvement of responsiveness in patients with disorders of consciousness.

Decannulation is a rehabilitation milestone in patients with Disorders of Consciousness (DoC). investigate the relationship between decannulation and improvement of responsiveness (IR) in DoC. 236 tracheostomized patients with severe Acquired Brain Injury and DoC admitted in the Intensive Rehabilitation Unit were retrospectively included. They received personalized interdisciplinary rehabilitation. At discharge, IR was evaluated. The association between IR and demographic/clinical data was investigated using a logistic regression analysis, both in the Unresponsive Wakefulness Syndrome (UWS) and Minimal Consciousness State (MCS) group, divided according to their Coma Recovery Scale-Revised score at admission. In the UWS group (N = 107), only decannulation was associated with IR at discharge (OR: 5.94, CI: 2.08-16.91, p = .001). In the MCS group (N = 129) time post-injury (OR: 0.983, CI: 0.97-0.99, p = .012) and decannulation were associated with IR at discharge (OR: 17.9, CI: 6.39-50.13, p < .001). Decannulation and IR were found to be strongly related, independently from the initial clinical state. While the retrospective nature of the study could not exclude that decannulation may be a consequence of a spontaneous recovery, the obtained results may disclose its potential influence on the clinical history of patients with DoC.

Gender differences in post-stroke functional outcome at discharge from an intensive rehabilitation hospital.

BACKGROUND: Gender differences in stroke functional recovery after rehabilitation are poorly investigated. Our aim was to compare functional outcomes at discharge from an intensive rehabilitation hospital after stroke in men and women, and to analyze their prognostic factors. METHODS: Retrospective observational study of consecutive stroke patients discharged from an intensive neurological rehabilitation hospital, from January 2018 to June 2019. Modified Rankin Scale (mRS) at discharge was the main outcome measure. RESULTS: Among the 208 included patients (mean age 73.4 ± 13.6 years), 105 (50.5%) were women. Women were significantly older (75.3 ± 13.8 vs. 71.4 ± 13.2 years, respectively, p = 0.041), and less often had a history of smoking habit (27% vs. 50%, p < 0.001). No gender differences emerged for vascular risk factors and comorbidities, pre-stroke functional status, length of hospital stay, stroke type, and number of clinical deficits. At admission to the rehabilitation hospital, mRS score distributions were not different (p = 0.795). At discharge, mRS score distributions and destinations did not differ between men and women (p = 0.391, p = 0.785, respectively). A significant interaction between gender and the change in mRS score from admission to discharge was found (F = 6.6, p = 0.011) taking into account age, stroke type, and number of initial clinical deficits. Dividing the cohort according to age, elderly women showed a better functional recovery compared to men. CONCLUSIONS: At admission to an intensive rehabilitation hospital, men and women presented a similar functional and clinical status and a substantial overlap of functional recovery after stroke. At higher ages, the potential for recovery appeared better in women compared to men.

Critical issue on the extinction and inattention subtest of NIHSS scale: an analysis on post-acute stroke patients attending inpatient rehabilitation.

OBJECTIVES: This study aims to evaluate the diagnostic performance of NIHSS extinction and inattention item, compared to the results of the Oxford Cognitive Screen (OCS) heart subtest. Additionally, the possible role of the NIHSS visual field subtest on the NIHSS extinction and inattention subtest performance is explored and discussed. METHODS: We analysed scores on NIHSS extinction and inattention subtest, NIHSS visual field subtest, and OCS heart subtest on a sample of 118 post-stroke patients. RESULTS: Compared to OCS heart subtest, the results on NIHSS extinction and inattention subtest showed an accuracy of 72.9% and a moderate agreement level (Cohen's kappa = 0.404). Furthermore, a decrease in NIHSS accuracy detecting neglect (61.1%) was observed in patients with pathological scores in NIHSS visual field item. CONCLUSIONS: Extreme caution is recommended for the diagnostic performance of extinction and inattention item of NIHSS. Signs of neglect may not be detected by NIHSS, and may be confused with visual field impairment. TRIAL REGISTRATION: This study refers to an observational study protocol submitted to ClinicalTrials.gov with identifier: NCT03968627 . The name of the registry is "Development of a National Protocol for Stroke Rehabilitation in a Multicenter Italian Institution" and the date of the registration is the 30th May 2019.

Electrodiagnostic findings in patients with non-COVID-19- and COVID-19-related acute respiratory distress syndrome.

BACKGROUND: Critical illness polyneuropathy and myopathy (CIPNM) is a frequent neurological manifestation in patients with acute respiratory distress syndrome (ARDS) from coronavirus disease 2019 (COVID-19) infection. CIPNM diagnosis is usually limited to clinical evaluation. We compared patients with ARDS from COVID-19 and other aetiologies, in whom a neurophysiological evaluation for the detection of CIPNM was performed. The aim was to determine if there were any differences between these two groups in frequency of CINPM and outcome at discharge from the intensive care unit (ICU). MATERIALS AND METHODS: This was a single-centre retrospective study performed on mechanically ventilated patients consecutively admitted (January 2016-June 2020) to the ICU of Careggi Hospital, Florence, Italy, with ARDS of different aetiologies. Neurophysiological evaluation was performed on patients with stable ventilation parameters, but marked widespread hyposthenia (Medical Research Council score <48). Creatine phosphokinase (CPK), lactic dehydrogenase (LDH) and mean morning glycaemic values were collected. RESULTS: From a total of 148 patients, 23 with COVID-19 infection and 21 with ARDS due to other aetiologies, underwent electroneurography/electromyography (ENG/EMG) recording. Incidence of CIPNM was similar in the two groups, 65% (15 of 23) in COVID-19 patients and 71% (15 of 21) in patients affected by ARDS of other aetiologies. At ICU discharge, subjects with CIPNM more frequently required ventilatory support, regardless the aetiology of ARDS. CONCLUSION: ENG/EMG represents a useful tool in the identification of the neuromuscular causes underlying ventilator wean failure and patient stratification. A high incidence of CIPNM, with a similar percentage, has been observed in ARDS patients of all aetiologies.

Impact of occupational complexity on cognitive decline in the oldest-old.

OBJECTIVES: The theory of "Cognitive Reserve" assumes that premorbid factors such as high educational and occupational attainment may enable a better way of coping with brain damage. It has been suggested that more stimulating lifestyles, including more complex work environments, may provide a buffer against cognitive decline in later life. This study aimed to investigate the association between occupational history and cognitive decline in a large cohort of Italian oldest-old. METHODS: 392 individuals (266 women/126 men, mean age 93 ± 3 years) enrolled in the "Mugello study" provided information about their work history. Jobs were classified in nine categories, according to the level of expertise required to perform them, as suggested by the Italian National Institute for Statistics (ISTAT). In addition, socio-demographic characteristics, comorbidities, level of independence, depression, and cognitive status were assessed. The presence of dementia was established based on cognitive status and independence in performing four selected instrumental activities of daily living (ability to manage telephone, transportation, medications, and budget). RESULTS: Neither work complexity (p = 0.995) nor work duration (p = 0.701) showed a significant effect on the likelihood of presenting a lower cognitive profile or developing dementia (p = 0.385 and p = 0.096, for work complexity and work duration, respectively). CONCLUSION: In the observed sample of oldest-old individuals, cognitive decline did not seem to be influenced by cognitive reserve as assessed through the evaluation of cognitive status and level of independence. It is conceivable that in this population, the decline of the brain reserve has a preponderant role in the definition of the cognitive profile.

Treatment of multiple sclerosis with rituximab: A multicentric Italian-Swiss experience.

BACKGROUND: Rituximab, an anti-CD20 monoclonal antibody leading to B lymphocyte depletion, is increasingly used as an off-label treatment option for multiple sclerosis (MS). OBJECTIVE: To investigate the effectiveness and safety of rituximab in relapsing-remitting (RR) and progressive MS. METHODS: This is a multicenter, retrospective study on consecutive MS patients treated off-label with rituximab in 22 Italian and 1 Swiss MS centers. Relapse rate, time to first relapse, Expanded Disability Status Scale (EDSS) progression, incidence of adverse events, and radiological outcomes from 2009 to 2019 were analyzed. RESULTS: A total of 355/451 enrolled subjects had at least one follow-up visit and were included in the outcome analysis. Annualized relapse rate significantly decreases after rituximab initiation versus the pre-rituximab start year in RRMS (from 0.86 to 0.09, p < .0001) and in secondary-progressive (SP) MS (from 0.34 to 0.06, p < .0001) and had a slight decrease in primary-progressive (PP) MS patients (from 0.12 to 0.07, p = 0.45). After 3 years from rituximab start, the proportion of patients with a confirmed EDSS progression was 14.6% in the RRMS group, 24.7% in the SPMS group, and 41.5% in the PPMS group. No major safety concerns arose. CONCLUSION: Consistently with other observational studies, our data show effectiveness of rituximab in reducing disease activity in patients with MS.

Critical illness polyneuromyopathy: Functional impact after severe acquired brain injuries.

OBJECTIVES: Critical illness polyneuropathy and myopathy (CIPNM) frequently affects critical patients and can occur after severe acquired brain injuries (sABI) influencing the functional recovery. We aimed to assess how the concomitance between CIPNM and sABI might influence the rehabilitative outcomes in terms of functional autonomy, oral feeding recovery and endotracheal tube weaning. MATERIALS AND METHODS: Adult patients with sABI admitted to an intensive rehabilitation unit and underwent an electromyography examination within seven days after admission were included. Assessed rehabilitative outcomes at discharge were decannulation success and its timing, functional autonomy measured by the Functional Independence Measure (FIM) and the Glasgow outcome scale expanded (GOS-E) and oral feeding recovery assessed by the Functional Oral Intake Scale (FOIS) score. RESULTS: Among the 224 included patients (81 (36%) females, age (median[IQR]): 68.73[21.66] years), 119 (53.1%) presented CIPNM at admission. Albeit the change of rehabilitative outcomes between admission and discharge was significant in all the sABI patients (P < .001 for ΔFOIS, ΔFIM and ΔGOS-E), those with a concomitant CIPNM achieved significantly lower scores as evaluated by Mann-Whitney tests (P < .001 for ΔFIM Δ and GOS-E; P < .005 for ΔFOIS). The CIPNM absence was associated with a higher probability to achieve functional autonomy (GOS-E > 4) (OR:4.57 (1.49/14.06); P < .01) and oral feeding recovery (FOIS ≥ 4) (OR:2.07 (1.07/3.99); P = .03) at discharge. CIPNM presence did not influence decannulation success but a longer time to cannula weaning was required (P < .01 in the log-rank test). CONCLUSIONS: CIPMN significantly affects the rehabilitative outcomes after a sABI and should be taken into account for better rehabilitative handling.

EEG and Coma Recovery Scale-Revised prediction of neurological outcome in Disorder of Consciousness patients.

OBJECTIVE: According to electroencephalogram (EEG) descriptors included in the American Clinical Neurophysiology Society (ACNS) terminology, we generated a score, and we compared it to the EEG scores previously proposed in order to identify the one with the best prognostic power for neurological outcome at post-acute stages in patients with severe disorders of consciousness (DoC). MATERIALS AND METHODS: Patients included in the analysis were clinically evaluated with the Coma Recovery Scale-Revised (CRS-R). An EEG was performed within the first week after admission to Intensive Rehabilitation Unit (IRU). EEGs were classified according to the ACNS terminology and to the scores of Bagnato and Estraneo. RESULTS: A total of 260 patients admitted to the IRU were analysed. A total of 160 patients (61%) improved their consciousness level during IRU stay. EEG score based on the ANCS terminology showed higher overall performance (receiver-operating area under the curve = 0.79) and greater sensitivity (65%), at comparable specificities (80%), for clinical improvement as compared to both CRS-R admission score and other EEG scores. Combining our EEG score with CRS-R score at admission, the cumulative sensitivity increased to 76% when at least one good prognostic index test was present in the same patient, whereas specificity increased up to 93% if both the good prognostic patterns of clinical and instrumental parameters were simultaneously present. CONCLUSION: The EEG scored according to the ACNS terminology is the best among those looked at for the prediction of short-term clinical improvement in patients with DoC and represents a useful instrumental test, complementary to clinical evaluation at admission, to be added in post-acute neurological prognostication methods.

Decannulation After a Severe Acquired Brain Injury.

OBJECTIVE: To identify the effect of some clinical characteristics of severe acquired brain injury (sABI) patients on decannulation success during their intensive rehabilitation unit (IRU) stay. DESIGN: Nonconcurrent cohort study. SETTING: Don Gnocchi Foundation Institute. PARTICIPANTS: Patients (N=351) with sABI and tracheostomy were retrospectively selected from the database of the IRU of the Don Gnocchi Foundation Institute. MAIN OUTCOME MEASURES: Potential predictors of decannulation were screened from variables collected at admission during clinical examination, conducted by trained and experienced examiners. The association between clinical characteristics and decannulation status was investigated through a Cox regression model. Kaplan-Meier curves were then created for time-event analysis. RESULTS: Among the patients (mean age, 64.1±15.5y), 54.1% were decannulated during their IRU stay. Absence of pulmonary infections (P<.001), sepsis (P=.001), tracheal alteration at the fibrobronchoscopy examination (P=.004) and a higher Coma Recovery Scale-Revised (CRS-R) score (P<.001) or a better state of consciousness at admission (P=.001) were associated with a higher probability of decannulation. CONCLUSIONS: Fibrobronchoscopy assessment of patency of airways and accurate evaluation of the state of consciousness using the CRS-R are relevant in this setting of care to better identify patients who are more likely to have the tracheostomy tube removed. These results may help clinicians choose the appropriate timing and intensity of rehabilitation interventions and plan for discharge.

Improvement on the Coma Recovery Scale-Revised During the First Four Weeks of Hospital Stay Predicts Outcome at Discharge in Intensive Rehabilitation After Severe Brain Injury.

OBJECTIVES: To evaluate the prognostic utility of serial assessment on the Coma Recovery Scale-Revised (CRS-R) during the first 4 weeks of intensive rehabilitation in patients surviving a severe brain injury. DESIGN: Prospective cohort study. SETTING: An intensive rehabilitation unit. PARTICIPANTS: Patients (N=110) consecutively admitted to the intensive rehabilitation unit. Inclusion criteria were (1) a diagnosis of unresponsive wakefulness syndrome (UWS) or minimally conscious state (MCS) caused by an acquired brain injury, and (2) aged >18 years. INTERVENTIONS: All patients underwent clinical evaluations using the Italian version of the CRS-R during the first month of hospital stay. MAIN OUTCOME MEASURES: Behavioral classification on the CRS-R and the score on the Glasgow Outcome Scale (GOS) at final discharge. Patients transitioning from UWS to MCS or emergence from MCS (E-MCS), and from MCS to E-MCS were classified as patients with improved responsiveness (IR). RESULTS: After a mean ± SD hospital stay of 5.3±2.7 months, 59 of 110 patients (53.6%) achieved IR. In the multivariable analysis, a higher CRS-R score change at week 4 (odds ratio =1.99; 95% confidence interval [CI], 1.49-2.66; P<.001) was the only significant predictor of IR at discharge. Fifty-three patients (48.2%) were classified as severely impaired at discharge (GOS=3). In the multivariable analysis, higher GOS scores were related to a higher CRS-R score at admission (B=.051; 95% CI, .027-.074; P<.001), a higher CRS-R score change at week 4 (B=.087; 95% CI, .064-.110; P<.001), and an absence of severe infections (B=-.477; 95% CI, -.778 to -.176; P=.002). CONCLUSIONS: An improvement on the total CRS-R score and on different subscales across the first 4 weeks of inpatient rehabilitation discriminates patients who will have a better outcome at discharge, providing information for rehabilitation planning and for communication with patients and their caregivers.

Score on Coma Recovery Scale-Revised at admission predicts outcome at discharge in intensive rehabilitation after severe brain injury.

OBJECTIVE: To assess the prognostic utility of the Coma Recovery Scale-Revised (CRS-R) in rehabilitation of patients surviving from severe brain injury. METHODS: In this prospective cohort study, all patients consecutively admitted to an Italian Intensive Rehabilitation Unit, with a diagnosis of unresponsive wakefulness syndrome (UWS) or minimally conscious state (MCS) due to acquired brain injury, underwent clinical evaluations using the Italian version of the CRS-R. At discharge, patients transitioning from UWS to MCS or emergence from MCS (E-MCS) and from MCS to E-MCS were classified as improved responsiveness (IR). Score on the Glasgow Outcome Scale (GOS) at discharge was recorded. RESULTS: In total, 137 (66 UWS, 71 MCS) subjects were enrolled. After a mean hospital stay of 5.3 ± 2.9 months, 81 (59.1%) patients achieved an IR. In the multivariable analysis, IR was associated with higher CRS-R score at admission (p = 0.002) and younger age at injury (p = 0.010). Moreover, higher GOS scores at discharge were related to younger age at injury (p = 0.018), shorter time post-onset (p = 0.003) and higher CRS-R score at admission (p < 0.001). CONCLUSIONS: Higher CRS-R scores at admission in intensive rehabilitation unit can help differentiate patients with better outcome at discharge, providing information for rehabilitation planning and communication with patients and their caregivers.

Appraisal of brain connectivity in radiologically isolated syndrome by modeling imaging measures.

We hypothesized that appraisal of brain connectivity may shed light on the substrate of the radiologically isolated syndrome (RIS), a term applied to asymptomatic subjects with brain MRI abnormalities highly suggestive of multiple sclerosis. We thus used a multimodal MRI approach on the human brain by modeling measures of microstructural integrity of white matter (WM) tracts with those of functional connectivity (FC) at the level of resting state networks in RIS subjects, demographically matched normal controls (NC), and relapsing-remitting (RR) MS patients, also matched with RIS for brain macrostructural damage (i.e., lesions and atrophy). Compared with NC, in both RIS subjects and MS patients altered integrity of WM tracts was present. However, RIS subjects showed, at a less conservative threshold, lower diffusivities than RRMS patients in distinct cerebral associative, commissural, projection, and cerebellar WM tracts, suggesting a relatively better anatomical connectivity. FC was similar in NC and RIS subjects, even in the presence of important risk factors for MS (spinal cord lesions, oligoclonal bands, and dissemination in time on MRI) and increased in RRMS patients in two clinically relevant networks subserving "processing" (sensorimotor) and "control" (working memory) functions. In RIS, the lack of functional reorganization in key brain networks may represent a model of "functional reserve," which may become upregulated, with an adaptive or maladaptive role, only at a later stage in case of occurrence of clinical deficit.

The cognitive reserve theory in the setting of pediatric-onset multiple sclerosis.

BACKGROUND: The study of cognitive reserve (CR) in relationship with cognitive impairment (CI) in pediatric-onset multiple sclerosis (POMS) may provide cues to identifying subjects at higher risk of impairment and scope for therapeutic strategies. OBJECTIVES: To assess the potential impact of CR on cognition in a cohort of POMS patients. METHODS: In all, 48 POMS patients were followed up for 4.7 ± 0.4 years. CI was defined as the failure of ⩾3 tests on an extensive neuropsychological battery. Change of neuropsychological performance was assessed through the Reliable Change Index (RCI) method. At baseline, CR was estimated by measuring the intelligence quotient (IQ). The relationships were assessed through multivariable regression analyses. RESULTS: At baseline, CI was detected in 14/48 (29.2%) patients. Two out of 57 healthy control (HC; 3.5%) met the same criteria of CI (p < 0.001). A deteriorating cognitive performance using the RCI method was observed in 18/48 patients (37.6%). Among the 34 cases who were cognitively preserved at baseline, a higher reserve predicted stable/improving performance (odds ratio (OR) = 1.11; 95% confidence interval (CI): 1.03-1.20; p = 0.006). CONCLUSION: Our results suggest that higher CR in POMS patients may protect from CI, particularly in subjects with initial cognitive preservation, providing relevant implications for counseling and rehabilitation strategies.