Oxidative Stress and Antioxidant Status in Adult Patients with Transfusion-Dependent Thalassemia: Correlation with Demographic, Laboratory, and Clinical Biomarkers.

Iron overload in beta transfusion-dependent thalassemia (ß-TDT) may provoke oxidative stress and reduction of the antioxidant defenses, with serious consequences for the disease course and complications. The present study evaluated the oxidant/antioxidant status of ß-TDT patients and its correlation with demographic, clinical, laboratory, and instrumental biomarkers. The OXY-adsorbent assay and the d-ROMs (Diacron, Grosseto, Italy) were evaluated in 58 ß-TDT patients (mean age: 37.55 ± 7.83 years, 28 females) enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network. Iron overload was quantified with R2* magnetic resonance imaging. Mean OXY was 323.75 ± 113.19 µmol HClO/mL and 39 (67.2%) patients showed a decreased OXY-Adsorbent level (<350 µmol HClO/mL), of whom 22 (37.9%) showed severely reduced levels. Mean d-ROMs was 305.12 ± 62.19 UA; 12 (20.7%) patients showed oxidative stress, and 4 (6.9%) elevated oxidative stress. OXY showed a significant negative correlation with global and segmental cardiac iron levels. D-ROMs levels significantly correlated with markers of cardiovascular risk (aging, glycemia, and N-terminal pro-B-type natriuretic peptide). Antioxidant depletion is frequent in ß-TDT patients, where OXY might serve as additive biomarker to assess heart iron status, whereas the d-ROMs might be helpful to assess the cardiovascular risk burden.

Impact of genotype on multi-organ iron and complications in patients with non-transfusion-dependent ß-thalassemia intermedia.

We evaluated the impact of the genotype on clinical and hematochemical features, hepatic and cardiac iron levels, and endocrine, hepatic, and cardiovascular complications in non-transfusion-dependent (NTD) ß-thalassemia intermedia (TI) patients. Sixty patients (39.09 ± 11.11 years, 29 females) consecutively enrolled in the Myocardial Iron Overload in Thalassemia project underwent Magnetic Resonance Imaging to quantify iron overload, biventricular function parameters, and atrial areas and to detect replacement myocardial fibrosis. Three groups of patients were identified: homozygous ß+ (N = 18), heterozygous ß0ß+ (N = 22), and homozygous ß0 (N = 20). The groups were homogeneous for sex, age, splenectomy, hematochemical parameters, chelation therapy, and iron levels. The homozygous ß° genotype was associated with significantly higher biventricular end-diastolic and end-systolic volume indexes and bi-atrial area indexes. No difference was detected in biventricular ejection fractions or myocardial fibrosis. Extramedullary hematopoiesis and leg ulcers were significantly more frequent in the homozygous ß° group compared to the homozygous ß+ group. No association was detected between genotype and liver cirrhosis, hypogonadism, hypothyroidism, osteoporosis, heart failure, arrhythmias, and pulmonary hypertension. Heart remodelling related to a high cardiac output state cardiomyopathy, extramedullary hematopoiesis, and leg ulcers were more pronounced in patients with the homozygous ß° genotype compared to the other genotypes analyzed. The knowledge of the genotype can assist in the clinical management of NTD ß-TI patients.

Free Thyroxine (fT4) as a Potential Biomarker of Neurological and Functional Outcome in Acquired Brain Injury: A Prospective Multicenter Cohort Study.

The potential involvement of thyroid hormones (THs) in the neurological and functional recovery of patients with brain damage has been hypothesized. We aimed at investigating the role of THs and their variations during the rehabilitation process as predictive biomarkers of neurological and functional outcome in patients with acquired brain injury (ABI). This prospective, multicenter cohort study included 220 patients with ABI consecutively admitted for a 6-month neurorehabilitation program. Data on the etiology of the brain injury, occurrence of seizures, neurosurgical procedures, and death during hospitalization were collected. Both at the baseline (T0) and at the end of the rehabilitation process (T1), the following variables were evaluated: thyroid function (TSH, fT4, and fT3) and outcome measure including the Glasgow Coma Scale (GCS), Glasgow Outcome Scale-Extended (GOS-E), and Functional Independence Measure (FIM) scale. During neurorehabilitation, a significant decrease in fT4 levels was documented in the population as a whole and in patients with severe ABI (p < 0.0001), whereas no significant variations were found in TSH and fT3 levels. No significant associations were found between THs and seizure occurrence, while the neurological and functional outcomes were associated with the variation in fT4 levels during rehabilitation. In particular, a higher magnitude of decrease in fT4 levels emerged as an independent predictor of more severe neurological damage (OR = 3.48, CI 95% 1.04-11.69, p = 0.04) and a lower functional recovery (ß = -0.22, p = 0.01). In conclusion, serum fT4 variation during neurorehabilitation could represent a potential biomarker of neurological and functional outcome in patients with ABI. Further studies are needed to investigate the mechanisms underlying this association.

Low Vitamin D Levels Are Associated with Increased Cardiac Iron Uptake in Beta-Thalassemia Major.

We evaluated the association of vitamin D and parathormone (PTH) levels with cardiac iron and function in beta-thalassemia major (ß-TM) patients. Two-hundred and seventy-eight TM patients (39.04 ± 8.58 years, 56.8% females) underwent magnetic resonance imaging for the assessment of iron overload (T2* technique), biventricular function parameters (cine images), and replacement myocardial fibrosis (late gadolinium enhancement technique). Vitamin D levels were deficient (<20 ng/dL) in 107 (38.5%) patients, insufficient (20-30 ng/dL) in 96 (34.5%) patients, and sufficient (≥30 ng/dL) in 75 (27.0%) patients. Deficient vitamin D patients had a significantly higher frequency of myocardial iron overload (MIO; global heart T2* < 20 ms) than patients with sufficient and insufficient vitamin D levels and a significantly higher left ventricular end-diastolic volume index and mass index than patients with sufficient vitamin D levels. PTH was not associated with cardiac iron, function, or fibrosis. In the multivariate regression analysis, vitamin D, serum ferritin, and pancreatic iron levels were the strongest predictors of global heart T2* values. In receiver operating characteristic curve analysis, a vitamin D level ≤ 17.3 ng/dL predicted MIO with a sensitivity of 81.5% and a specificity of 75.3% (p < 0.0001). In TM, the periodic and regular assessment of vitamin D levels can be beneficial for the prevention of cardiac iron accumulation and subsequent overt dysfunction.

Phenotypic Clustering of Beta-Thalassemia Intermedia Patients Using Cardiovascular Magnetic Resonance.

We employed an unsupervised clustering method that integrated demographic, clinical, and cardiac magnetic resonance (CMR) data to identify distinct phenogroups (PGs) of patients with beta-thalassemia intermedia (ß-TI). We considered 138 ß-TI patients consecutively enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) Network who underwent MR for the quantification of hepatic and cardiac iron overload (T2* technique), the assessment of biventricular size and function and atrial dimensions (cine images), and the detection of replacement myocardial fibrosis (late gadolinium enhancement technique). Three mutually exclusive phenogroups were identified based on unsupervised hierarchical clustering of principal components: PG1, women; PG2, patients with replacement myocardial fibrosis, increased biventricular volumes and masses, and lower left ventricular ejection fraction; and PG3, men without replacement myocardial fibrosis, but with increased biventricular volumes and masses and lower left ventricular ejection fraction. The hematochemical parameters and the hepatic and cardiac iron levels did not contribute to the PG definition. PG2 exhibited a significantly higher risk of future cardiovascular events (heart failure, arrhythmias, and pulmonary hypertension) than PG1 (hazard ratio-HR = 10.5; p = 0.027) and PG3 (HR = 9.0; p = 0.038). Clustering emerged as a useful tool for risk stratification in TI, enabling the identification of three phenogroups with distinct clinical and prognostic characteristics.

Investigating microRNAs as biomarkers in disorders of consciousness: a longitudinal multicenter study.

MicroRNAs (miRNAs) are involved in gene regulation and may affect secondary brain injury and recovery in patients with disorders of consciousness (DoC). This study investigated the role of five miRNAs (150-5p, 132-3p, 23b-3p, 451a, and 16-5p) in prolonged DoC. miRNA levels were assessed in serum samples from 30 patients with unresponsive wakefulness syndrome or minimally conscious state due to traumatic or hypoxic-ischemic brain injury (TBI, HIBI) at baseline (1-3 months) and 6 months post-injury. Patients' diagnoses were determined using the Coma Recovery Scale revised, and functional outcomes were evaluated 6 months after injury with the Glasgow Outcome Scale Extended (GOSE) and the Functional Independence Measure (FIM). Compared to healthy controls, patients with TBI had lower levels of miRNAs 150-5p, 132-3p, and 23b-3p at baseline, while patients with HIBI had lower levels of miRNA 150-5p at baseline and 6 months post-injury and a reduction of miRNA 451a at baseline. Higher levels of miRNAs 132-3p and 23b-3p were associated with better outcomes in TBI patients as indicated by GOSE and FIM scores. This study highlights distinct miRNA dysregulated patterns in patients with prolonged DoC, dependent on etiology and post-injury time, and suggests that miRNAs 132-3p and 23b-3p may serve as prognostic biomarkers.

A novel digital approach for post-stroke cognitive deficits: a pilot study.

BACKGROUND: Cognitive dysfunctions after a brain stroke have a huge impact on patients' disability and activities of daily living. Prism adaptation (PA) is currently used in patients with right brain damage to improve lateralized spatial attentional deficits. Recent findings suggest that PA could also be useful for rehabilitation of other cognitive functions. OBJECTIVE: In the present study, we tested for the efficacy on cognitive rehabilitation of a novel device in which the procedure of prism adaptation is digitized and followed by cognitive training of attention and executive functions using serious games. METHODS: Thirty stroke patients were randomly assigned to two groups: an experimental group of 15 patients, which performed the experimental rehabilitation training using the novel device in 10 consecutive daily sessions; a control group of 15 patients, which performed the routine cognitive training in 10 consecutive daily sessions. Both groups were tested before and after the rehabilitation program on neuropsychological tests (digit and spatial span forward and backward, attentional matrices, Stroop task) and on functional scales (Barthel index and Beck Anxiety Index). RESULTS: The main results showed that only patients who received the experimental rehabilitation training improved their scores on tests of digit span forward, spatial span backward, attentional matrices and Stroop. Moreover, patients of the experimental but not of the control group showed a significant correlation between improvement on some tasks (mainly spatial span backward) and improvement on activities of daily living as well as with reduction of anxiety levels. CONCLUSIONS: These results suggest that combining digital PA with cognitive training using serious games may be added in clinical settings for cognitive rehabilitation of stroke patients, with beneficial effects extending in promoting independency in activities of daily living and reduction of psychiatric symptoms.

Cerebrospinal Fluid and Blood Biomarkers in Patients with Post-Traumatic Disorders of Consciousness: A Scoping Review.

(1) Background: Cerebrospinal fluid (CSF) and blood biomarkers are emerging tools used to obtain information on secondary brain damage and to improve diagnostic and prognostic accuracy for patients with prolonged post-traumatic disorders of consciousness (DoC). We synthesized available data from studies evaluating CSF and blood biomarkers in these patients. (2) Methods: A scoping review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist to identify and synthesize data from relevant studies. Studies were identified by PubMed and manual searches. Those involving patients with unresponsive wakefulness syndrome or in a minimally conscious state for >28 days, evaluating CSF or blood biomarkers, and conducted on patients with traumatic brain injuries older than 16 years were included in the review. (3) Results: In total, 17 studies were included. Findings on neurofilament light chain, proteins, metabolites, lipids, amyloid-ß, tau, melatonin, thyroid hormones, microtubule-associated protein 2, neuron-specific enolase, and brain-derived neurotrophic factor were included in the qualitative synthesis. (4) Conclusions: The most promising applications for CSF and blood biomarkers are the monitoring of secondary neurodegeneration, support of DoC diagnoses, and refinement of prognoses, although current evidence remains too scarce to recommend such uses of these biomarkers in clinical practice.

Prognostic value of multiparametric cardiac magnetic resonance in sickle cell patients.

The aim of this multicenter study was to prospectively assess the predictive value of multiparametric cardiac magnetic resonance (CMR) for cardiovascular complications in sickle cell disease (SCD) patients. Among all patients with hemoglobinopathies consecutively enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) Network, we selected 102 SCD patients (34.38 ± 12.67 years, 49 females). Myocardial iron overload (MIO) was measured by the multislice multiecho T2* technique. Atrial dimensions and biventricular function parameters were quantified by cine images. Late gadolinium enhancement (LGE) images were acquired to detect focal myocardial fibrosis. At baseline CMR, only two patients had significant MIO (global heart T2* < 20 ms). During a mean follow-up of 63.01 ± 24.95 months, 11 cardiovascular events (10.8%) were registered: 3 pulmonary hypertension, 2 supraventricular arrhythmias, 1 heart failure, 1 death for heart failure, 1 pulmonary embolism, 1 peripheral vascular disease, 1 transient ischemic attack, and 1 death after acute chest syndrome. In the multivariate analysis, the independent CMR predictors of cardiovascular events were left ventricular (LV) ejection fraction (hazard ratio-HR = 0.88; p = 0.025) and right ventricular (RV) mass index (HR = 1.09; p = 0.047). According to the receiver-operating characteristic curve analysis for adverse events, an LV ejection fraction < 58.9% and an RV mass index > 31 g/m2 were optimal cut-off values. Reduced left ventricular ejection fraction and increased right ventricular mass index showed a significant prognostic value in patients with SCD. Our data seem to suggest that CMR may be added as a screening tool for identifying SCD patients at high risk for cardiopulmonary and vascular diseases.

Impact of seizures and their prophylaxis with antiepileptic drugs on rehabilitation course of patients with traumatic or hemorrhagic brain injury.

Objective: To determine whether, in patients undergoing rehabilitation after traumatic or hemorrhagic brain injury, seizures and the use of antiepileptic drugs (AEDs) negatively impact on functional outcome, and, in turn, whether prophylactic AED therapy can prevent the development of seizures. Design: Observational retrospective study. Setting: Highly specialized inpatient neurorehabilitation clinic. Participants: Patients with traumatic brain injury (TBI), or hemorrhagic stroke (HS) consecutively admitted to our neurorehabilitation unit between January 1, 2009, and December 31, 2018. Main measures and variables: Patients' demographic data, neurological status (Glasgow Coma Scale), and rehabilitation outcome (Functional Independence Measure scale), both assessed on admission and on discharge, associated neurosurgical procedures (craniectomy, or cranioplasty), AED use, early or late seizures occurrence, and death during hospitalization. Results: Of 740 patients, 162 (21.9%) had seizures, and prophylactic AEDs were started in 192 (25.9%). Multivariate logistic regression identified severity of brain injury as a risk factor for acute symptomatic seizures (ASS) in HS (OR = 1.800, 95%CI = 1.133-1.859, p = 0.013), and for unprovoked seizures (US) in TBI (OR = 1.679, 95%CI = 1.062-2.655, p = 0.027). Prophylaxis with AEDs reduced ASS frequency, but, if protracted for months, was associated with US occurrence (HS, p < 0.0001; TBI, p = 0.0002; vs. untreated patients). Presence of US (ß = -0.12; p < 0.0001) and prophylaxis with AEDs (ß = -0.09; p = 0.002), were associated with poor functional outcome, regardless of age, severity of brain insult, and HS vs. TBI subtype. Conclusions: Severity of brain injury and occurrence of seizures during neurorehabilitation are the main driver of poor outcome in both HS and TBI. The possible detrimental role on the epileptogenic and functional outcome played by seizures prophylaxis with AEDs, nonetheless useful to prevent ASS if administered over the first week after the brain injury, warrants further investigation.

Diagnostic and therapeutic recommendations in adult dystonia: a joint document by the Italian Society of Neurology, the Italian Academy for the Study of Parkinson's Disease and Movement Disorders, and the Italian Network on Botulinum Toxin.

The diagnostic framework and the therapeutic management of patients with adult dystonia can represent a challenge for clinical neurologists. The objective of the present paper is to delineate diagnostic and therapeutic recommendations for dystonia provided by a panel of Italian experts afferent to the Italian Society of Neurology, the Italian Academy for the Study of Parkinson's Disease and Movement Disorders, and the Italian Network on Botulinum Toxin. We first discuss the clinical approach and the instrumental assessment useful for diagnostic purpose. Then, we analyze the pharmacological, surgical, and rehabilitative therapeutic options for adult dystonia. Finally, we propose a hospital-territory network model for adult dystonia management.

Six-month outcomes in patients with hemorrhagic and non-hemorrhagic traumatic disorders of consciousness.

BACKGROUND: Intracranial hematomas (IHs) occur commonly after severe traumatic brain injury, but their effects on outcomes in patients with prolonged disorders of consciousness (DoC) following coma (i.e., unresponsive wakefulness syndrome and minimally conscious state) are unknown. METHODS: In this multicenter longitudinal study, we compared clinical outcomes and serum neurofilament light chain (NFL) levels of 52 patients with traumatic DoC with (n = 35) and without (n = 17) IH in the acute phase. Patients were evaluated with the Coma Recovery Scale-Revised (CRS-R) at enrollment (1-3 months post-injury) and with the CRS-R, extended Glasgow Outcome Scale (GOSE), and Functional Independence Measure (FIM) at 6 months post-injury. At the same timepoints, serum NFL levels were compared between patients with and without IHs and with those of 52 sex- and age-matched healthy controls. RESULTS: Patients with and without IH did not differ in terms of DoC or CRS-R scores at admission, or clinical outcomes (death, unresponsive wakefulness syndrome, minimally conscious state, or emergence from minimally conscious state) or CRS-R, GOSE, or FIM scores 6 months post-injury. NFL levels were significantly higher in patients than in controls at admission and 6 months post-injury (both p < 0.0001), but they did not differ between patients with and without IH. CONCLUSIONS: This study showed that IHs do not affect clinical outcomes or markers of axonal degeneration in patients with traumatic DoC.

Thyrotropic Axis and Disorders of Consciousness in Acquired Brain Injury: A Potential Intriguing Association?

Purpose: A potential involvement of thyrotropic axis in influencing the state of consciousness could be hypothesized. We aimed at investigating thyroid function tests as predictors of disorders of consciousness (DoC) and relating recovery in a large cohort of patients with DoC secondary to acquired brain injury (ABI). Methods: This retrospective, multicenter, cohort study included 151 patients with DoC following ABI, consecutively admitted for a 6-month neurorehabilitation program. Data on etiology of brain injury, evolution of DoC, disability and rehabilitation assessments, and death during rehabilitation were collected at baseline and on discharge. Thyroid function tests (serum TSH, fT4 and fT3 levels) were assessed on admission in all patients and at final discharge in 50 patients. Results: Lower baseline TSH levels and greater TSH increments (ΔTSH) after neurorehabilitation predicted a favorable change in DoC independent of age, sex, BMI, etiology of brain injury and initial DoC subtype (TSH: OR=0.712, CI 95% 0.533-0.951, p=0.01; ΔTSH: OR=2.878, CI 95% 1.147-7.223, p=0.02). On the other hand, neither fT4 nor fT3 or their variations appeared to play any role on DoC changes after 6-months inpatient neurorehabilitation. A lower magnitude of ΔfT4 acted as a strong predictor of improved functional disability level (ß=0.655, p=0.002) and cognitive functions (ß=-0.671, p=0.003), implying that smaller changes in fT4 were associated with higher outcomes. Conclusions: Serum TSH levels assessed in the subacute post-ABI phase and its variation during neurorehabilitation could represent a potential biomarker of DoC evolution, while variations in fT4 levels seem to be associated with rehabilitation and cognitive functions. Further studies are needed to investigate the mechanisms underlying these associations.

Biomarkers of Brain Injury: A Window on Mechanisms of Injury and Recovery in the Brain.

The decision-making process regarding management after severe acute brain injury is based on clinical evaluation and depends on the injury etiology as well as radiological and neurophysiological data [...].

The role of plasticity in the recovery of consciousness.

Disorders of consciousness (DOCs), i.e., coma, vegetative state, and minimally conscious state are the consequences of a severe brain injury that disrupts the brain ability to generate consciousness. Recovery from DOCs requires functional and structural changes in the brain. The sites where these plastic changes take place vary according to the pathophysiology of the DOC. The ascending reticular activating system of the brainstem and its complex connections with the thalamus and cortex are involved in the pathophysiology of coma. Subcortical structures, such as the striatum and globus pallidus, together with thalamocortical and corticothalamic projections, the basal forebrain, and several networks among different cortical areas are probably involved in vegetative and minimally conscious states. Some mechanisms of plasticity that allegedly operate in each of these sites to promote recovery of consciousness will be discussed in this chapter. While some mechanisms of plasticity work at a local level, others produce functional changes in complex neuronal networks, for example by entraining neuronal oscillations. The specific mechanisms of brain plasticity represent potential targets for future treatments aiming to restore consciousness in patients with severe DOCs.

Risk factors for 2-year mortality in patients with prolonged disorders of consciousness: An international multicentre study.

BACKGROUND AND PURPOSE: Patients with prolonged disorders of consciousness (pDoC) have a high mortality rate due to medical complications. Because an accurate prognosis is essential for decision-making on patients' management, we analysed data from an international multicentre prospective cohort study to evaluate 2-year mortality rate and bedside predictors of mortality. METHODS: We enrolled adult patients in prolonged vegetative state/unresponsive wakefulness syndrome (VS/UWS) or minimally conscious state (MCS) after traumatic and nontraumatic brain injury within 3 months postinjury. At enrolment, we collected demographic (age, sex), anamnestic (aetiology, time postinjury), clinical (Coma Recovery Scale-Revised [CRS-R], Disability Rating Scale, Nociception Coma Scale-Revised), and neurophysiologic (electroencephalogram [EEG], somatosensory evoked and event-related potentials) data. Patients were followed up to gather data on mortality up to 24 months postinjury. RESULTS: Among 143 traumatic (n = 55) and nontraumatic (n = 88) patients (VS/UWS, n = 68, 19 females; MCS, n = 75, 22 females), 41 (28.7%) died within 24 months postinjury. Mortality rate was higher in VS/UWS (42.6%) than in MCS (16%; p < 0.001). Multivariate regression in VS/UWS showed that significant predictors of mortality were older age and lower CRS-R total score, whereas in MCS female sex and absence of alpha rhythm on EEG at study entry were significant predictors. CONCLUSIONS: This study demonstrated that a feasible multimodal assessment in the postacute phase can help clinicians to identify patients with pDoC at higher risk of mortality within 24 months after brain injury. This evidence can help clinicians and patients' families to navigate the complex clinical decision-making process and promote an international standardization of prognostic procedures for patients with pDoC.

Predicting Long-Term Recovery of Consciousness in Prolonged Disorders of Consciousness Based on Coma Recovery Scale-Revised Subscores: Validation of a Machine Learning-Based Prognostic Index.

Prognosis of prolonged Disorders of Consciousness (pDoC) is influenced by patients' clinical diagnosis and Coma Recovery Scale-Revised (CRS-R) total score. We compared the prognostic accuracy of a novel Consciousness Domain Index (CDI) with that of clinical diagnosis and CRS-R total score, for recovery of full consciousness at 6-, 12-, and 24-months post-injury. The CDI was obtained by a combination of the six CRS-R subscales via an unsupervised machine learning technique. We retrospectively analyzed data on 143 patients with pDoC (75 in Minimally Conscious State; 102 males; median age = 53 years; IQR = 35; time post-injury = 1-3 months) due to different etiologies enrolled in an International Brain Injury Association Disorders of Consciousness Special Interest Group (IBIA DoC-SIG) multicenter longitudinal study. Univariate and multivariate analyses were utilized to assess the association between outcomes and the CDI, compared to clinical diagnosis and CRS-R. The CDI, the clinical diagnosis, and the CRS-R total score were significantly associated with a good outcome at 6, 12 and 24 months. The CDI showed the highest univariate prediction accuracy and sensitivity, and regression models including the CDI provided the highest values of explained variance. A combined scoring system of the CRS-R subscales by unsupervised machine learning may improve clinical ability to predict recovery of consciousness in patients with pDoC.

COVID-19 Neuromuscular Involvement in Post-Acute Rehabilitation.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with muscle and nerve injuries as a consequence of prolonged critical illness or the infection itself. In this study, we evaluated neuromuscular involvement in patients who underwent post-acute intensive rehabilitation after COVID-19. METHODS: Clinical and neurophysiological evaluations, including nerve conduction studies and electromyography, were performed on 21 consecutive patients admitted for rehabilitation after COVID-19. RESULTS: Clinical signs suggesting muscle or nerve involvement (weakness, reduced deep tendon reflexes, impaired sensitivity, abnormal gait) were found in 19 patients. Neurophysiological examinations confirmed neuromuscular involvement in 17 patients: a likely association of critical illness myopathy (CIM) and critical illness polyneuropathy (CIP) was found in 5 patients; CIM alone was found in 4 patients; axonal sensory-motor polyneuropathy was found in 4 patients (CIP in 2 patients, metabolic polyneuropathy in 2 patients); Guillain-Barré syndrome was found in 2 patients (classical demyelinating sensory-motor polyneuropathy and acute motor axonal neuropathy, respectively); peroneal nerve injury was found in 1 patient; and pre-existing L4 radiculopathy was found in 1 patient. CONCLUSIONS: Neuromuscular involvement is a very common finding among patients admitted for rehabilitation after COVID-19, and proper investigation should be conducted when muscle or nerve injury is suspected for adequate rehabilitative strategy planning.