Brain-Computer Interfaces for Communication in Patients with Disorders of Consciousness: A Gap Analysis and Scientific Roadmap.

BACKGROUND: We developed a gap analysis that examines the role of brain-computer interfaces (BCI) in patients with disorders of consciousness (DoC), focusing on their assessment, establishment of communication, and engagement with their environment. METHODS: The Curing Coma Campaign convened a Coma Science work group that included 16 clinicians and neuroscientists with expertise in DoC. The work group met online biweekly and performed a gap analysis of the primary question. RESULTS: We outline a roadmap for assessing BCI readiness in patients with DoC and for advancing the use of BCI devices in patients with DoC. Additionally, we discuss preliminary studies that inform development of BCI solutions for communication and assessment of readiness for use of BCIs in DoC study participants. Special emphasis is placed on the challenges posed by the complex pathophysiologies caused by heterogeneous brain injuries and their impact on neuronal signaling. The differences between one-way and two-way communication are specifically considered. Possible implanted and noninvasive BCI solutions for acute and chronic DoC in adult and pediatric populations are also addressed. CONCLUSIONS: We identify clinical and technical gaps hindering the use of BCI in patients with DoC in each of these contexts and provide a roadmap for research aimed at improving communication for adults and children with DoC, spanning the clinical spectrum from intensive care unit to chronic care.

Measuring Salivary Cortisol to Assess the Effect of Natural Environments on Stress Level in Acute Patients With Severe Brain Injuries: An Exploratory Study.

BACKGROUND: Salivary cortisol is a safe and non-invasive measure of hypothalamic-pituitary-adrenal axis function and is used as a biomarker of the human stress response. Natural environments are recognized to contribute to help reduce the effect of stress. OBJECTIVE: To determine the feasibility of a salivary cortisol collection protocol for acute severely brain-injured patients, and to explore the influence of exposure to natural settings on salivary cortisol concentration as an index of stress level. METHODS: An exploratory study on 17 acute patients with severe brain injury was performed. We collected salivary samples in a closed hospital ward and a therapeutic garden at the start of the session and after 30 minutes of rest time. Physiological parameters, level of communication, and subjective well-being were also assessed. RESULTS: The primary objectives regarding the feasibility of the protocol were met overall. We found no significant differences in cortisol values when including the whole population. However, cortisol values were significantly higher in the indoor environment in patients with communication attempts. CONCLUSIONS: A salivary collection protocol with brain-injured patients in the acute phase is feasible and safe, and this type of measurement could pave the way for future research supporting the benefits of nature as an additional resource in their neurorehabilitation.

Guideline on multimodal rehabilitation for patients with post-intensive care syndrome.

BACKGROUND: Intensive Care Unit (ICU) survivors often experience several impairments in their physical, cognitive, and psychological health status, which are labeled as post-intensive care syndrome (PICS). The aim of this work is to develop a multidisciplinary and -professional guideline for the rehabilitative therapy of PICS. METHODS: A multidisciplinary/-professional task force of 15 healthcare professionals applied a structured, evidence-based approach to address 10 scientific questions. For each PICO-question (Population, Intervention, Comparison, and Outcome), best available evidence was identified. Recommendations were rated as "strong recommendation", "recommendation" or "therapy option", based on Grading of Recommendations, Assessment, Development and Evaluation principles. In addition, evidence gaps were identified. RESULTS: The evidence resulted in 12 recommendations, 4 therapy options, and one statement for the prevention or treatment of PICS. RECOMMENDATIONS: early mobilization, motor training, and nutrition/dysphagia management should be performed. Delirium prophylaxis focuses on behavioral interventions. ICU diaries can prevent/treat psychological health issues like anxiety and post-traumatic stress disorders. Early rehabilitation approaches as well as long-term access to specialized rehabilitation centers are recommended. Therapy options include additional physical rehabilitation interventions. Statement: A prerequisite for the treatment of PICS are the regular and repeated assessments of the physical, cognitive and psychological health in patients at risk for or having PICS. CONCLUSIONS: PICS is a variable and complex syndrome that requires an individual multidisciplinary, and multiprofessional approach. Rehabilitation of PICS should include an assessment and therapy of motor-, cognitive-, and psychological health impairments.

Terson Syndrome: Not to Be Missed in Patients with Disorders of Consciousness.

The diagnosis of clinical cognitive motor dissociation (cCMD) can be hindered by pitfalls during standardized clinical evaluation based on gold-standard neurobehavioral rating scales. We introduce here a new pitfall, by reporting two cases of Terson syndrome (TS) after subarachnoid haemorrhage (SAH) caused by the rupture of an anterior communicant artery aneurysm, hospitalized in the Acute Neurorehabilitation Unit (ANR) of CHUV. TS is reported to occur in 8-19.3% of patients suffering from SAH. It can lead to significant visual impairment and if unrecognized, may impair the patient's capacity to interact appropriately with the environment; it thus presents an important pitfall in recognizing clinical cognitive-motor dissociation (cCMD) in patients with altered states of consciousness. An early ophthalmological exam should be considered in all patients with SAH and disorders of consciousness or visual complaints.

Feasibility study of the Nox-T3 device to detect swallowing and respiration pattern in neurologically impaired patients in the acute phase.

Dysphagia is a frequent complication in neurologically impaired patients, which can lead to aspiration pneumonia and thus prolonged hospitalization or even death. It is essential therefore, to detect and assess dysphagia early for best patient care. Fiberoptic endoscopic and Videofluoroscopy evaluation of swallowing are the gold standard exams in swallowing studies but neither are perfectly suitable for patients with disorders of consciousness (DOC). In this study, we aimed to find the sensitivity and specificity of the Nox-T3 sleep monitor for detection of swallowing. A combination of submental and peri-laryngeal surface electromyography, nasal cannulas and respiratory inductance plethysmography belts connected to Nox-T 3 allows recording swallowing events and their coordination with breathing, providing time-coordinated patterns of muscular and respiratory activity. We compared Nox-T3 swallowing capture to manual swallowing detection on fourteen DOC patients. The Nox-T3 method identified swallow events with a sensitivity of 95% and a specificity of 99%. In addition, Nox-T3 has qualitative contributions, such as visualization of the swallowing apnea in the respiratory cycle which provide additional information on the swallowing act that is useful to clinicians in the management and rehabilitation of the patient. These results suggest that Nox-T3 could be used for swallowing detection in DOC patients and support its continued clinical use for swallowing disorder investigation.

A Biopsychosocial Evaluation of Post-Acute Outcome of Patients with Severe Brain Lesions Recovering from Coma: An Exploratory Study.

Currently, very little is known about the holistic outcome of patients recovering from coma. The aim of this retrospective exploratory study was to evaluate the outcomes of patients recovering from coma after care in an acute neurorehabilitation unit with particular focus on their biopsychosocial and spiritual needs in the post-acute phase of recovery. We included 12 patients and evaluated clinical outcome evolution by comparing standard neurobehavioral scores from patient files measured in the acute and post-acute phases. We assessed patient needs using the Quality of Life after Brain Injury scale (QOLIBRI) and classified self-reported complaints mentioned in patient files according to the International Classification of Functioning, Disability and Health framework (ICF). Mean patient evolution was a Level of Cognitive Functioning Scale (LCF)-r increase of 3.33 levels (range = 2); a Disability Rating Scale score (DRS) of -3.27 points (SD = 3.78); a Functional Ambulation Classification (FAC) scale score of 1.83 (range = 5); and a Glasgow Outcome Scale (GOS) median = 0 (Interquartile range = 1). Main patient complaints concerned mental functioning (n = 7), sensory functioning and pain (n = 6), neuromusculoskeletal and movement problems (n = 5), and major life areas (n = 5). To conclude, a significant handicap that affects their daily life was present in the post-acute phase in most patients. Complaints involved biopsychosocial and spiritual elements. The neurobehavioral scale results do not necessarily correlate with the subjective representations patients had of their condition.

Structural connectivity in recovery after coma: Connectome atlas approach.

AIM: Pathological states of recovery after coma as a result of a severe brain injury are marked with changes in structural connectivity of the brain. This study aimed to identify a topological correlation between white matter integrity and the level of functional and cognitive impairment in patients recovering after coma. METHODS: Structural connectomes were computed based on fractional anisotropy maps from 40 patients using a probabilistic human connectome atlas. We used a network based statistics approach to identify potential brain networks associated with a more favorable outcome, assessed with clinical neurobehavioral scores at the patient's discharge from the acute neurorehabilitation unit. RESULTS: We identified a subnetwork whose strength of connectivity correlated with a more favorable outcome as measured with the Disability Rating Scale (network based statistics: t >3.5, P =.010). The subnetwork predominated in the left hemisphere and included the thalamic nuclei, putamen, precentral and postcentral gyri, and medial parietal regions. Spearman correlation between the mean fractional anisotropy value of the subnetwork and the score was ρ = -0.60 (P <.0001). A less extensive overlapping subnetwork correlated with the Coma Recovery Scale Revised score, consisting mostly of the left hemisphere connectivity between the thalamic nuclei and pre- and post-central gyri (network based statistics: t >3.5, P =.033; Spearman's ρ = 0.58, P <.0001). CONCLUSION: The present findings suggest an important role of structural connectivity between the thalamus, putamen and somatomotor cortex in the recovery from coma as evaluated with neurobehavioral scores. These structures are part of the motor circuit involved in the generation and modulation of voluntary movement, as well as the forebrain mesocircuit supposedly underlying the maintenance of consciousness. As behavioural assessment of consciousness depends heavily on the signs of voluntary motor behaviour, further work will elucidate whether the identified subnetwork reflects the structural architecture underlying the recovery of consciousness or rather the ability to communicate its content.

A Focus on Subtle Signs and Motor Behavior to Unveil Awareness in Unresponsive Brain-Impaired Patients: The Importance of Being Clinical.

Brain-injured patients in a state of cognitive motor dissociation (CMD) exhibit a lack of command following using conventional neurobehavioral examination tools but a high level of awareness and language processing when assessed using advanced imaging and electrophysiology techniques. Because of their behavioral unresponsiveness, patients with CMD may seem clinically indistinguishable from those with a true disorder of consciousness that affects awareness on a substantial level (coma, vegetative state/unresponsive wakefulness state, or minimally conscious state minus). Yet, by expanding the range of motor testing across limb, facial, and ocular motricity, we may detect subtle, purposeful movements even in the subset of patients classified as vegetative state/unresponsive wakefulness state. We propose the term of clinical CMD to describe patients showing these slight but determined motor responses and exhibiting a characteristic akinetic motor behavior as opposed to a pyramidal motor system behavior. These patients may harbor hidden cognitive capabilities and significant potential for a good long-term outcome. Indeed, we envision CMD as ranging from complete (no motor response) to partial (subtle clinical motor response) forms, falling within a spectrum of progressively better motor output in patients with considerable cognitive capabilities. In addition to providing a decisional flowchart, we present this novel approach to classification as a graphical model that illustrates the range of clinical manifestations and recovery trajectories fundamentally differentiating true disorders of consciousness from the spectrum of CMD.

Early detection of ICU-acquired weakness in septic shock patients ventilated longer than 72 h.

PURPOSE: ICU-acquired weakness, comprising Critical Illness Polyneuropathy (CIP) and Myopathy (CIM) is associated with immobilization and prolonged mechanical ventilation. This study aims to assess feasibility of early detection of CIP and CIM by peroneal nerve test (PENT) and sensory sural nerve action potential (SNAP) screening in patients with septic shock and invasively ventilated for more than 72 h. METHODS: We performed repetitive PENT screening from 72 h after intubation until detecting a pathological response. We tested SNAPs in pathological PENT to differentiate CIP from CIM. We performed muscle strength examination in awake patients and recorded time from intubation to first in-bed and out-of-bed mobilization. RESULTS: Eighteen patients were screened with PENT and 88.9% had abnormal responses. Mean time between intubation and first screening was 94.38 (± 22.41) hours. Seven patients (38.9%) had CIP, two (11.1%) had CIM, one (5.6%) had CIP and CIM, six (33.3%) had a pathological response on PENT associated with ICU-acquired weakness (but no SNAP could be performed to differentiate between CIP and CIM) and two patients had (11.1%) had no peripheral deficit. In patients where it could be performed, muscle strength testing concorded with electrophysiological findings. Twelve patients (66.7%) had out-of-bed mobilization 10.8 (± 7.4) days after admission. CONCLUSION: CIP and CIM are frequent in septic shock patients and can be detected before becoming symptomatic with simple bedside tools. Early detection of CIP and CIM opens new possibilities for their timely management through preventive measures such as passive and active mobilization.

Clinical Cognitive Motor Dissociation: A Case Report Showing How Pitfalls Can Hinder Early Clinical Detection of Awareness.

This study presents the case of a brain-injured patient whose pathological awakening after coma and absence of interaction led to a diagnosis of lack of consciousness when standard clinical scales were administered. However, we were able to demonstrate conscious perception in this patient from initial clinical assessments using the Motor Behaviour Tool in the acute stage, complemented by a systematic search for potential obstacles blocking his execution of motor responses (pitfalls). This refinement of the diagnosis enabled prediction of a favourable outcome despite the severity of the lesions, with the patient's evolution confirming our prediction. Faced with an unresponsive patient, every specialist should go beyond the absence of response with the standard scores, consider the possibility of a hidden consciousness and look for rigorous ways of proving it.

Movement-Related Cortical Potentials in Embodied Virtual Mirror Visual Feedback.

Background: Mirror therapy is thought to drive interhemispheric communication, resulting in a balanced activation. We hypothesized that embodied virtual mirror visual feedback (VR-MVF) presented on a computer screen may produce a similar activation. In this proof-of-concept study, we investigated differences in movement-related cortical potentials (MRCPs) in the electroencephalogram (EEG) from different visual feedback of user movements in 1 stroke patient and 13 age-matched adults. Methods: A 60-year-old right-handed (Edinburgh score >95) male ischemic stroke [left paramedian pontine, National Institutes of Health Stroke Scale (NIHSS) = 6] patient and 13 age-matched right-handed (Edinburgh score >80) healthy adults (58 ± 9 years; six female) participated in the study. We recorded 16-electrode electroencephalogram (EEG), while participants performed planar center-out movements in two embodied visual feedback conditions: (i) direct (movements translated to the avatar's ipsilateral side) and (ii) mirror (movements translated to the avatar's contralateral side) with left (direct left/mirror left) or right (direct right/mirror right) arms. Results: As hypothesized, we observed more balanced MRCP hemispheric negativity in the mirror right compared to the direct right condition [statistically significant at the FC4 electrode; 99.9% CI, (0.81, 13)]. MRCPs in the stroke participant showed reduced lateralized negativity in the direct left (non-paretic) situation compared to healthy participants. Interestingly, the potentials were stronger in the mirror left (non-paretic) compared to direct left case, with significantly more bilateral negativity at FC3 [95% CI (0.758 13.2)] and C2 [95% CI (0.04 9.52)]. Conclusions: Embodied mirror visual feedback is likely to influence bilateral sensorimotor cortical subthreshold activity during movement preparation and execution observed in MRCPs in both healthy participants and a stroke patient.

Disentangling the percepts of illusory movement and sensory stimulation during tendon vibration in the EEG.

Mechanical vibration of muscle tendons in specific frequencies - termed functional proprioceptive stimulation (FPS) - has the ability to induce the illusion of a movement which is congruent with a lengthening of the vibrated tendon and muscle. The majority of previous reports of the brain correlates of this illusion are based on functional neuroimaging. Contrary to the electroencephalogram (EEG) however, such technologies are not suitable for bedside or ambulant use. While a handful of studies have shown EEG changes during FPS, it remains underinvestigated whether these changes were due to the perceived illusion or the perceived vibration. Here, we aimed at disentangling the neural correlates of the illusory movement from those produced by the vibration sensation by comparing the neural responses to two vibration types, one that did and one that did not elicit an illusion. We recruited 40 naïve participants, 20 for the EEG experiment and 20 for a supporting behavioral study, who received functional tendon co-vibration on the biceps and triceps tendon at their left elbow, pseudo-randomly switching between the illusion and non-illusion trials. Time-frequency decomposition uncovered a strong and lasting event-related desynchronization (ERD) in the mu and beta band in both conditions, suggesting a strong somatosensory response to the vibration. Additionally, the analysis of the evoked potentials revealed a significant difference between the two experimental conditions from 310 to 990ms post stimulus onset. Training classifiers on the frequency-based and voltage-based correlates of illusion perception yielded above chance accuracies for 17 and 13 out of the 20 subjects respectively. Our findings show that FPS-induced illusions produce EEG correlates that are distinct from a vibration-based control and which can be classified reliably in a large number of participants. These results encourage pursuing EEG-based detection of kinesthetic illusions as a tool for clinical use, e.g., to uncover aspects of cognitive perception in unresponsive patients.

European Academy of Neurology and European Federation of Neurorehabilitation Societies guideline on pharmacological support in early motor rehabilitation after acute ischaemic stroke.

BACKGROUND AND PURPOSE: Early pharmacological support for post-stroke neurorehabilitation has seen an abundance of mixed results from clinical trials, leaving practitioners at a loss regarding the best options to improve patient outcomes. The objective of this evidence-based guideline is to support clinical decision-making of healthcare professionals involved in the recovery of stroke survivors. METHODS: This guideline was developed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework. PubMed, Cochrane Library and Embase were searched (from database inception to June 2018, inclusive) to identify studies on pharmacological interventions for stroke rehabilitation initiated in the first 7 days (inclusive) after stroke, which were delivered together with neurorehabilitation. A sensitivity analysis was conducted on identified interventions to address results from breaking studies (from end of search to February 2020). RESULTS: Upon manually screening 17,969 unique database entries (of 57,001 original query results), interventions underwent meta-analysis. Cerebrolysin (30 ml/day, intravenous, minimum 10 days) and citalopram (20 mg/day, oral) are recommended for clinical use for early neurorehabilitation after acute ischaemic stroke. The remaining interventions identified by our systematic search are not recommended for clinical use: amphetamine (5, 10 mg/day, oral), citalopram (10 mg/day, oral), dextroamphetamine (10 mg/day, oral), Di-Huang-Yi-Zhi (2 × 18 g/day, oral), fluoxetine (20 mg/day, oral), lithium (2 × 300 mg/day, oral), MLC601(3 × 400 mg/day, oral), phosphodiesterase-5 inhibitor PF-03049423 (6 mg/day, oral). No recommendation 'for' or 'against' is provided for selegiline (5 mg/day, oral). Issues with safety and tolerability were identified for amphetamine, dextroamphetamine, fluoxetine and lithium. CONCLUSIONS: This guideline provides information for clinicians regarding existing pharmacological support in interventions for neurorecovery after acute ischaemic stroke. Updates to this material will potentially elucidate existing conundrums, improve current recommendations, and hopefully expand therapeutic options for stroke survivors.

Case Report: Behavioral Unresponsiveness in Acute COVID-19 Patients: The Utility of the Motor Behavior Tool-Revised and 18F-FDG PET/CT.

Along with the propagation of COVID-19, emerging evidence reveals significant neurological manifestations in severely infected COVID-19 patients. Among these patients admitted to the intensive care unit (ICU), behavioral unresponsiveness may occur frequently, yet, there are still only a few cases reported and with rare descriptions of their motor behavior after pathological awakening. Several hypotheses regarding central lesions in these patients are conceivable. Here, we describe two acute SARS-CoV-2- infected patients who developed neurological symptoms evoking the condition of clinical cognitive motor dissociation (CMD). This diagnosis could be confirmed first by clinical observation of a dissociation between preserved cognitive abilities and lack of initial motor interaction and second, by performing 18F- FDG PET imaging. Accurate diagnosis led to an appropriate neuro-rehabilitation regimen with long-term neuro-rehabilitation leading to an improved outcome for both patients.

[Neurorehabilitation in the acute and post-acute phase: what did we learn from the first wave of COVID-19?] / Neurorééducation en phases aiguë et postaiguë : qu'avons-nous appris de la première vague de Covid-19 ?

The majority of patients with Coronavirus disease 2019 (COVID-19) present mild to moderate illness and recover without hospitalization. Nevertheless, 5 % of cases require hospitalization in the intensive care unit, with 15 % of them showing severe central and peripheral nervous system manifestations. These patients should be considered high risk patients and their management must include prevention of a potential accompanying cascade of negative factors. In order to optimize care, it is essential that signs of neurological damage are searched for as early as in intensive care so that appropriate neurorehabilitation can be started immediately and continued in a specific unit for patients with neurological sequelae at post-acute and outpatient phases.

La majorité des patients atteints par la maladie due au coronavirus 2019 (Covid-19) présente une évolution plutôt favorable. Cependant 5 % nécessitent une hospitalisation aux soins intensifs, dont 15 % présentent des atteintes sévères des systèmes nerveux central et périphérique. Ces patients doivent être considérés comme des personnes à haut risque de développer des séquelles graves et leur plan de traitement doit nécessairement impliquer la prévention d'une potentielle cascade de facteurs négatifs concomitants. Afin d'optimiser une telle prise en charge, il est primordial que les premiers signes d'atteintes neurologiques soient détectés dès les soins intensifs et qu'une neurorééducation puisse être débutée précocement et poursuivie dans une filière de patients neuro-lésés en phase postaiguë, puis en ambulatoire.

Discriminating cognitive motor dissociation from disorders of consciousness using structural MRI.

An accurate evaluation and detection of awareness after a severe brain injury is crucial to a patient's diagnosis, therapy, and end-of-life decisions. Misdiagnosis is frequent as behavior-based assessments often overlook subtle signs of consciousness. This study aimed to identify brain MRI characteristics of patients with residual consciousness after a severe brain injury and to develop a simple MRI-based scoring system according to the findings. We retrieved data from 128 patients and split them into a development or validation set. Structural brain MRIs were qualitatively assessed for lesions in 18 brain regions. We used logistic regression and support vector machine algorithms to first identify the most relevant brain regions predicting a patient's outcome in the development set. We next built a diagnostic MRI-based score and estimated its optimal diagnostic cut-off point. The classifiers were then tested on the validation set and their performance compared using the receiver operating characteristic curve. Relevant brain regions predicting negative outcome highly overlapped between both classifiers and included the left mesencephalon, right basal ganglia, right thalamus, right parietal cortex, and left frontal cortex. The support vector machine classifier showed higher accuracy (0.93, 95% CI: 0.81-0.96) and specificity (0.97, 95% CI: 0.85-1) than logistic regression (accuracy: 0.87, 95% CI: 0.73 - 0.95; specificity: 0.90, 95% CI: 0.75-0.97), but equal sensitivity (0.67, 95% CI: 0.24-0.94 and 0.22-0.96, respectively) for distinguishing patients with and without residual consciousness. The novel MRI-based score assessing brain lesions in patients with disorders of consciousness accurately detects patients with residual consciousness. It could complement valuably behavioral evaluation as it is time-efficient and requires only conventional MRI.

Early discrimination of cognitive motor dissociation from disorders of consciousness: pitfalls and clues.

Bedside assessment of consciousness and awareness after a severe brain injury might be hampered by confounding clinical factors (i.e., pitfalls) interfering with the production of behavioral or motor responses to external stimuli. Despite the use of validated clinical scales, a high misdiagnosis rate is indeed observed. We retrospectively analyzed a cohort of 49 patients with severe brain injury admitted to an acute neuro-rehabilitation program. Patients' behavior was assessed using the Motor Behavior Tool and Coma Recovery Scale Revised. All patients underwent systematic assessment for pitfalls including polyneuropathy and/or myopathy and/or myelopathy, major cranial nerve palsies, non-convulsive status epilepticus, aphasia (expressive or comprehensive), cortical blindness, thalamic involvement and frontal akinetic syndrome. A high prevalence (75%) of pitfalls potentially interfering with sensory afference (polyneuropathy, myopathy, myelopathy, and sensory aphasia), motor efference (polyneuropathy, myopathy, motor aphasia, and frontal akinetic syndrome), and intrinsic brain activity (thalamic involvement and epilepsy) was found. Nonetheless, the motor behavior tool identified residual cognition (i.e. a cognitive motor dissociation condition) regardless of the presence of these pitfalls in 70% of the patients diagnosed as unresponsive using the Coma Recovery Scale Revised. On one hand, pitfalls might contribute to misdiagnosis. On the other, it could be argued that they are clues for diagnosing cognitive motor dissociation rather than true disorders of consciousness given their prominent effect on the sensory-motor input-output balance.

Intensive Care Admission and Early Neuro-Rehabilitation. Lessons for COVID-19?

Coronavirus disease 2019 (COVID-19) requires admission to intensive care (ICU) for the management of acute respiratory distress syndrome in about 5% of cases. Although our understanding of COVID-19 is still incomplete, a growing body of evidence is indicating potential direct deleterious effects on the central and peripheral nervous systems. Indeed, complex and long-lasting physical, cognitive, and functional impairments have often been observed after COVID-19. Early (defined as during and immediately after ICU discharge) rehabilitative interventions are fundamental for reducing the neurological burden of a disease that already heavily affects lung function with pulmonary fibrosis as a possible long-term consequence. In addition, ameliorating neuromuscular weakness with early rehabilitation would improve the efficiency of respiratory function as respiratory muscle atrophy worsens lung capacity. This review briefly summarizes the polymorphic burden of COVID-19 and addresses possible early interventions that could minimize the neurological and systemic impact. In fact, the benefits of early multidisciplinary rehabilitation after an ICU stay have been shown to be advantageous in several clinical conditions making an early rehabilitative approach generalizable and desirable to physicians from a wide range of different specialties.