Functional outcome after inpatient rehabilitation in postintensive care unit COVID-19 patients: findings and clinical implications from a real-practice retrospective study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic is quickly spreading worldwide, with survivors that suffer functional impairments with a consequent key role of rehabilitation in this context. To date, there is a lack of findings on the role of rehabilitation in postacute COVID-19 patients. AIM: Thus, we aimed at describing the role of a patient-tailored rehabilitation plan on functional outcome in hospitalized COVID-19 patients. DESIGN: Real-practice retrospective study. SETTING: Inpatients Rehabilitation Unit. POPULATION: Postacute COVID-19 patients. METHODS: Medical records of patients referred to an Italian COVID-19 Rehabilitation Unit from March 10th, 2020 to April 30th, 2020 were collected. All patients underwent a rehabilitative (30 minutes/set, 2 times/day), aimed to improve gas exchanges, reducing dyspnoea, and improving muscle function. At the admission (T0) and at the discharge (T1), we evaluated as outcome measures: Barthel Index (BI), modified Medical Research Council Dyspnea Scale, 6-Minute Walking Test (6-MWT) and Borg Rating of Perceived Exertion (RPE) scale. We also assessed: type of respiratory supports needed, pulmonary function, coagulation and inflammation markers and length of stay (LOS) in Rehabilitation Unit. RESULTS: We included 41 postacute COVID-19 patients (25 male and 19 female), mean aged 72.15±11.07 years. Their mean LOS in the Rehabilitation Unit was 31.97±9.06 days, as 39 successfully completed the rehabilitation treatment and 2 deceased. We found statistically significant improvement in BI (84.87±15.56 vs. 43.37±26.00; P<0.0001), 6-MWT (303.37±112.18 vs. 240.0±81.31 meters; P=0.028), Borg RPE scale (12.23±2.51 vs. 16.03±2.28; P<0.0001). CONCLUSIONS: These findings suggest that postacute COVID-19 patients might beneficiate of a motor and respiratory rehabilitation treatment. However, further studies are advised to better understand long-term sequelae of the disease. CLINICAL REHABILITATION IMPACT: This study provides evidence on the role of rehabilitation COVID-19 postacute inpatients through a patient-tailored treatment.

Reply to Comment on "Environmental and Occupational Risk Factors of Amyotrophic Lateral Sclerosis: A Population-Based Case-Control Study".

We much appreciate the positive comments and interest concerning our study on the environmental and occupational risk factors of amyotrophic lateral sclerosis (ALS) [...].

Early rehabilitation in post-acute COVID-19 patients: data from an Italian COVID-19 Rehabilitation Unit and proposal of a treatment protocol.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic is quickly spreading, putting under heavy stress health systems worldwide and especially Intensive Care Units (ICU). Rehabilitation Units have a crucial role in reducing disability in order to reintroduce patients in the community. AIM: The aim of this study is to characterize pulmonary function and disability status and to propose an early rehabilitation protocol in a cohort of post-acute COVID-19 patients admitted to an Italian Rehabilitation Unit. DESIGN: Cross-sectional observational study. SETTING: Inpatients Rehabilitation Unit. POPULATION: Post-acute COVID-19 patients. METHODS: Demographic, anamnestic and clinical characteristics, laboratory exams and medical imaging findings were collected for the entire cohort. Outcome measures evaluated at the admission in Rehabilitation Unit were: type of respiratory supports needed, fraction of inspired oxygen (FiO2), partial pressure of oxygen (PaO2), FiO2/PaO2, Barthel Index (BI), modified Medical Research Council (mMRC) Dyspnoea Scale, and 6-Minute Walking Test (6-MWT). Furthermore, we proposed an early rehabilitation protocol for COVID-19 patients based on baseline FiO2. RESULTS: We included 32 post-acute COVID-19 patients (22 male and 10 female), mean aged 72.6±10.9 years. BI was 45.2±27.6, with patients in need of higher FiO2 (≥40%) showing lower values: 39.6±25.7 vs. 53.3±29.3. All patients had grade 4 or 5 on the mMRC Dyspnea Scale. Only 14 COVID-19 patients were able to walk (43.7%). 6-MWT was feasible in 6 (18.8%) patients with a mean distance of 45.0±100.6 meters. CONCLUSIONS: Taken together, our findings suggest that post-acute COVID-19 patients suffered from dyspnea and shortness of breath even for minimal activities, with a resulting severe disability, and only a few of them were able to perform 6-MWT with poor results. An early rehabilitation protocol was proposed according to the baseline conditions of the patients. CLINICAL REHABILITATION IMPACT: This study could provide an accurate description of COVID-19 sub-acute patients admitted to a Rehabilitation Unit along with a proposal of treatment to help physicians to tailor the best possible rehabilitative treatment.

Environmental and Occupational Risk Factors of Amyotrophic Lateral Sclerosis: A Population-Based Case-Control Study.

Objectives: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease with still unknown etiology. We aimed at investigating the association between environmental and occupational factors with ALS risk. Methods: We performed a population-based case-control study in four Italian provinces (Catania, Modena, Novara, and Reggio Emilia) by administration of tailored questionnaires to ALS cases (n = 95) and randomly selected population referents (n = 135). We estimated ALS risk by calculating the odds ratio (OR) with its 95% confidence interval (CI) using an unconditional logistic regression model. Results: We found a positive association with disease risk for history of occupation in the agricultural sector (OR = 2.09, 95% CI 0.79-7.54), especially for longer than 10 years (OR = 2.72, 95% 1.02-7.20). Overall occupational exposure to solvents also suggested a positive association, especially for thinners (OR = 2.27, 95% CI 1.14-4.54) and paint removers (OR = 2.01, 95% CI 0.90-4.48). Both occupational and environmental exposure to electromagnetic fields show a slightly increased risk with OR = 1.69 (95% CI 0.70-4.09) and 2.41 (95% CI 1.13-5.12), respectively. Occupational but not environmental exposure to pesticides (OR = 1.22, 95% CI 0.63-2.37), particularly fungicides, and exposure to metals (OR = 4.20, 95% CI 1.88-9.38), particularly lead, mercury, and selenium, showed an imprecise but positive association. Finally, there was an indication of increased risk for living in proximity to water bodies. Conclusions: Despite the caution that needs to be used due to some study limitations, such as the low number of exposed subjects and the possibility of recall bias, these results suggest the potential role of some environmental and occupational factors in ALS etiology.

Clinical and Lifestyle Factors and Risk of Amyotrophic Lateral Sclerosis: A Population-Based Case-Control Study.

Background: Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disease of the motor neurons. The etiology of ALS remains largely unknown, particularly with reference to the potential environmental determinants. Methods: We performed a population-based case-control study in four provinces from both Northern and Southern Italy in order to assess non-genetic ALS risk factors by collecting through tailored questionnaires information about clinical and lifestyle factors. We estimated ALS risk by calculating odds ratio (OR) with its 95% confidence interval (CI) using unconditional logistic regression models adjusted for sex, age and educational attainment. Results: We recruited 230 participants (95 cases and 135 controls). We found a possible positive association of ALS risk with trauma, particularly head trauma (OR = 2.61, 95% CI 1.19-5.72), electric shock (OR = 2.09, 95% CI 0.62-7.06), and some sports, although at a competitive level only. In addition, our results suggest an increased risk for subjects reporting use of private wells for drinking water (OR = 1.38, 95% CI 0.73-2.27) and for use of herbicides during gardening (OR = 1.95, 95% CI 0.88-2.27). Conversely, there was a suggestion of an inverse association with overall fish consumption (OR = 0.27, 95% CI 0.12-0.60), but with no dose-response relation. Consumption of some dietary supplements, namely those containing amino acids and, in the Southern Italy population, vitamins and minerals such as selenium, seemed associated with a statistically imprecise increased risk. Conclusions: Our results suggest a potential etiologic role a number of clinical and lifestyle factors with ALS risk. However, caution is needed due to some study limitations. These include the small sample size and the low number of exposed subjects, which affect statistical precision of risk estimates, the potential for exposure misclassification, and the uncertainties about mechanisms underpinning the possible association between these factors and disease risk.

Instrumental or Physical-Exercise Rehabilitation of Balance Improves Both Balance and Gait in Parkinson's Disease.

We hypothesised that rehabilitation specifically addressing balance in Parkinson's disease patients might improve not only balance but locomotion as well. Two balance-training protocols (standing on a moving platform and traditional balance exercises) were assessed by assigning patients to two groups (Platform, n = 15, and Exercises, n = 17). The platform moved periodically in the anteroposterior, laterolateral, and oblique direction, with and without vision in different trials. Balance exercises were based on the Otago Exercise Program. Both platform and exercise sessions were administered from easy to difficult. Outcome measures were (a) balancing behaviour, assessed by both Index of Stability (IS) on platform and Mini-BESTest, and (b) gait, assessed by both baropodometry and Timed Up and Go (TUG) test. Falls Efficacy Scale-International (FES-I) and Parkinson's Disease Questionnaire (PDQ-8) were administered. Both groups exhibited better balance control, as assessed both by IS and by Mini-BESTest. Gait speed at baropodometry also improved in both groups, while TUG was less sensitive to improvement. Scores of FES-I and PDQ-8 showed a marginal improvement. A four-week treatment featuring no gait training but focused on challenging balance tasks produces considerable gait enhancement in mildly to moderately affected patients. Walking problems in PD depend on postural instability and are successfully relieved by appropriate balance rehabilitation. This trial is registered with ClinicalTrials.gov NCT03314597.

Development of a System Architecture for Evaluation and Training of Proprioceptive Deficits of the Upper Limb.

Proprioception plays a fundamental role in maintaining posture and executing movement, and the quantitative evaluation of proprioceptive deficits in poststroke patients is important. But currently it is not widely performed due to the complexity of the evaluation tools required for a reliable assessment. The aims of this pilot study were to (a) develop a system architecture for upper limb evaluation and training of proximal and distal sense of position in the horizontal plane and (b) test the system in healthy and pathological subjects. Two robotic devices for evaluation and training of, respectively, wrist flexion/extension and shoulder-elbow manipulation were employed. The system we developed was applied in a group of 12 healthy subjects and 10 patients after stroke. It was able to quantitatively evaluate upper limb sense of position in the horizontal plane thanks to a set of quantitative parameters assessing position estimation errors, variability, and gain. In addition, it was able to distinguish healthy from pathological conditions. The system could thus be a reliable method to detect changes in the sense of position of patients with sensory deficits after stroke and could enable the implementation of novel training approaches for the recovery of normal proprioception.

Assessment of dexterity and diagnostic accuracy of the Functional Dexterity Test in patients with carpal tunnel syndrome. / Valutazione della destrezza e accuratezza diagnostic del Functional Dexterity Test in soggetti affetti da syndrome del tunnel carpale.

BACKGROUND: The diagnosis of carpal tunnel syndrome (STC) is centered on the symptoms. However, patients also show an impairment of sensorimotor functions, but the relationship between STC and manual dexterity has never been investigated. OBJECTIVES: To analyze the correlation between manual dexterity and severity of the STC. Another objective was the diagnostic accuracy of the clinical battery including provocative tests (Phalen, Tinel) and Functional Dexterity Test (FDT). METHODS: A sample of 80 subjects with suspected STC was subdivided into 4 groups based on EMG (severe/extreme-GrA, moderate-GrB, mild/minimal-GrC, negative-GrD) and evaluated in blind by Phalen, Tinel and FDT. The relationship between the FDT and the allocation of subjects was investigated by Spearman's rho, while the groups were compared with univariate ANOVA and Tukey's post hoc analysis. Diagnostic accuracy of the clinical battery was expressed by sensitivity, specificity, and likelihood ratios (LR). RESULTS: A moderate (r=0.48, p minor of 0.001) correlation was found between FDT and the 4 groups. ANOVA has returned a significant difference between GrA vs. all others and between GrB vs. GrD. The battery showed a sensitivity, specificity, positive likelihood ratio (LR+) and negative likelihood ratio (LR-) of 70%, 94%, 11.98 and 0.31 respectively. CONCLUSIONS: The results of this study supported the hypothesis that STC patients also have a dexterity impairment. The FDT was able to discriminate between three levels of severity (negative, mild to moderate, severe to extreme), maintaining a good level of diagnostic accuracy in addition to provocative tests.

Secular Trends of Amyotrophic Lateral Sclerosis: The Piemonte and Valle d'Aosta Register.

Importance: This study reports the long-term epidemiologic trends of amyotrophic lateral sclerosis (ALS) based on a prospective register. Objective: To examine the 20-year epidemiologic trends of ALS in the Piemonte and Valle d'Aosta regions of Italy. Design, Setting, and Participants: The Piemonte and Valle d'Aosta Register for ALS (PARALS) is an epidemiologic prospective register that covers 2 Italian regions (population of 4 476 931 inhabitants according to the 2011 census) from January 1, 1995, through December 31, 2014. Case ascertainment is based on multiple sources (neurologic departments, hospital discharge archives, and mortality records). Incidence rates are age and sex standardized for the Italian population of the 2011 census. Age-period-cohort (APC) analysis was performed using a Poisson regression model. Main Outcomes and Measures: The primary study outcomes were long-term incidence and prevalence rates of ALS using a prospective design and their determinants. Results: During the study period, a total of 2702 patients (mean [SD] age at onset, 65.7 [11.1] years; 1246 [46.1%] female and 1456 [53.9%] male) received a diagnosis of ALS between 1995 and 2014, corresponding to a crude annual incidence rate of 3.03 per 100 000 population (95% CI, 2.85-3.23) and an adjusted incidence rate of 2.78 per 100 000 population (95% CI, 2.57-2.96). The age-adjusted incidence rate increased in the 2 decades of the study (1995-2004: 2.66; 95% CI, 2.50-2.83; 2005-2014: 2.89; 95% CI, 2.71-3.07; P = .04), mostly in women. The adjusted rate ratio of men to women decreased from 1.27:1 (1995-2004) to 1.17:1 (2005-2014). The analysis of deviance for the APC regression models indicated that the drift variable is relevant in explaining the variation of ALS incidence rates over time in the overall population (change in deviance, 4.6553; P = .03) and in women (change in deviance, 3.8821; P = .05) but not in men (change in deviance, 0.77215; P = .38). A total of 479 patients with ALS were alive and had not undergone tracheostomy at the prevalence day (December 31, 2014), corresponding to a crude prevalence rate of 10.54 per 100 000 population (95% CI, 9.64-11.52). Conclusions and Relevance: During the 1995 to 2014 period, the crude and adjusted incidences of ALS increased in Piemonte and Valle d'Aosta, mostly in women. The APC model revealed that the increase of ALS incidence is attributable to a birth cohort effect in women, with a peak in the 1930 cohort. The different increase of ALS incidence in men and women points to an effect of exogenous factors with a differential effect on the 2 sexes, acting on a genetic background.

Influence of arterial hypertension, type 2 diabetes and cardiovascular risk factors on ALS outcome: a population-based study.

OBJECTIVE: To assess the prognostic influence of pre-morbid type 2 diabetes mellitus, arterial hypertension and cardiovascular (CV) risk profile on ALS phenotype and outcome in a population-based cohort of Italian patients. METHODS: A total of 650 ALS patients from the Piemonte/Valle d'Aosta Register for ALS, incident in the 2007-2011 period, were recruited. Information about premorbid presence of type 2 diabetes mellitus, arterial hypertension was collected at the time of diagnosis. Patients' CV risk profile was calculated according to the Joint British Societies' guidelines on prevention of cardiovascular disease in clinical practice (JBS2). RESULTS: At the univariate analysis, the presence of pre-morbid arterial hypertension was associated with a higher age at onset of ALS and a shorter survival, and patients with a high CV risk profile had a worse prognosis than those with a low CV risk profile. The Cox multivariable analysis did not confirm such findings. Type 2 diabetes mellitus did not modify either the phenotype or the prognosis of ALS patients. CONCLUSIONS: This study performed on a large population-based cohort of ALS patients has demonstrated that arterial hypertension, type 2 diabetes and CV risk factors, calculated using the Framingham equation, do not influence ALS phenotype and prognosis.

Curved Walking Rehabilitation with a Rotating Treadmill in Patients with Parkinson's Disease: A Proof of Concept.

Training subjects to step-in-place eyes open on a rotating platform while maintaining a fixed body orientation in space [podokinetic stimulation (PKS)] produces a posteffect consisting in inadvertent turning around while stepping-in-place eyes closed [podokinetic after-rotation (PKAR)]. Since the rationale for rehabilitation of curved walking in Parkinson's disease is not fully known, we tested the hypothesis that repeated PKS favors the production of curved walking in these patients, who are uneasy with turning, even when straight walking is little affected. Fifteen patients participated in 10 training sessions distributed in 3 weeks. Both counterclockwise and clockwise PKS were randomly administered in each session. PKS velocity and duration were gradually increased over sessions. The velocity and duration of the following PKAR were assessed. All patients showed PKAR, which increased progressively in peak velocity and duration. In addition, before and at the end of the treatment, all patients walked overground along linear and circular trajectories. Post-training, the velocity of walking bouts increased, more so for the circular than the linear trajectory. Cadence was not affected. This study has shown that parkinsonian patients learn to produce turning while stepping when faced with appropriate training and that this capacity translates into improved overground curved walking.

Incidence of amyotrophic lateral sclerosis in the province of Novara, Italy, and possible role of environmental pollution.

OBJECTIVE AND METHODS: Based on nationwide death certificates, a cluster of amyotrophic lateral sclerosis (ALS) has been reported in the area of Briga (Novara province, northern Italy), known for its severe environmental contamination. We further investigated this finding, by following up with the collection of recent incidence ALS data in 2002-2012 of Novara province, also to assess the possible long-term effects of environmental pollution in that area. RESULTS: In the whole Novara province we identified 106 ALS cases, of which 35 were from the Briga area. Incidence rates of Novara province were 3.98, 5.14 and 2.97 for the total population, males and females, respectively, compared with the Briga area where they were 4.65, 4.27 and 4.98, respectively. The ratio of observed-to-expected ALS cases in the Briga area, using incidence of the rest of Novara province as a reference, was 1.17 (95% CI 0.81-1.62), with a value of 0.83 (95% CI 0.47-1.37) in males and 1.68 (95% CI 1.03-2.60) in females. CONCLUSIONS: Overall, our study did not confirm previous findings of an excess ALS incidence in an area characterised by severe environmental heavy metal pollution, and it suggests the need to interpret with caution clusters identified through mortality data.

Comparison of exercise training effect with different robotic devices for upper limb rehabilitation: a retrospective study.

BACKGROUND: Several robotic devices have been proposed for upper limb rehabilitation, but they differ in terms of application fields and the technical solutions implemented. AIM: The aim of this study was to compare the effectiveness of three different robotic devices for shoulder-elbow rehabilitation in reducing motor impairment and improving motor performance in post-stroke patients. DESIGN: Retrospective multi-center study. SETTING: Inpatient rehabilitation hospital. POPULATION: Eighty-seven chronic and subacute post-stroke patients, aged 48-85 years. METHODS: Data were obtained through a retrospective analysis of patients who underwent a 3-week rehabilitation program including robot-assisted therapy of the upper limb and conventional physical therapy. Patients were divided into three groups according to the robot device used for exercise training: 'Braccio di Ferro" (BdF), InMotion2 (IMT), and MEchatronic system for MOtor recovery after Stroke (MEMOS). They were evaluated at the beginning and end of treatment using the Fugl-Meyer (FM) and Modified Ashworth (MAS) clinical scales and by a set of robot measured kinematic parameters. RESULTS: The three groups were homogeneous for age, level of impairment, time since the acute event, and spasticity level. A significant effect of time (P<0.001) was evident on FM and kinematic parameters across all groups. The average change in the FM score was 9.5, 7.3 and 7.1 points, respectively, for BdF, IMT and MEMOS. No significant between-group differences were observed at the MAS pre- vs. post-treatment. A significant interaction between time and groups resulted for the mean velocity (MV, P<0.005) and movement smoothness parameters (nPK, P<0.001 and SM, P<0.02). The effect size (ES) was large for the FM score and MV parameter, independently of the type of robot device used. Further, the ES ranged from moderate to large for the remaining kinematic parameters except for the movement accuracy (mean distance, MD), which exhibited a small ES in the BdF and MEMOS groups. CONCLUSIONS: The motor function gains obtained during robot-assisted therapy of stroke patients seem to be independent of the type of robot device used for the training program. All devices tested in this study were effective in improving the level of impairment and motor performance. CLINICAL REHABILITATION IMPACT: This study could help rehabilitation professionals to set-up comparative studies involving rehabilitation technologies.

Influence of cigarette smoking on ALS outcome: a population-based study.

OBJECTIVE: To assess the prognostic influence of premorbid smoking habits and vascular risk profile on amyotrophic lateral sclerosis (ALS) phenotype and outcome in a population-based cohort of Italian patients. METHODS: A total of 650 patients with ALS from the Piemonte/Valle d'Aosta Register for ALS, incident in the 2007-2011 period, were recruited. Information about premorbid cigarette smoking habits and chronic obstructive pulmonary disease (COPD) were collected at the time of diagnosis. RESULTS: Current smokers had a significantly shorter median survival (1.9 years, IQR 1.2-3.4) compared with former (2.3 years, IQR 1.5-4.2) and never smokers (2.7 years, IQR 1.8-4.6) (p=0.001). Also COPD adversely influenced patients' prognosis. Both smoking habits and CODP were retained in Cox multivariable model. CONCLUSIONS: This study has demonstrated in a large population-based cohort of patients with ALS that cigarette smoking is an independent negative prognostic factor for survival, with a dose-response gradient. Its effect is not related to the presence of COPD or to respiratory status at time of diagnosis. The understanding of the mechanisms, either genetic or epigenetic, through which exogenous factors influence disease phenotype is of major importance towards a more focused approach to cure ALS.

Intensive cycle ergometer training improves gait speed and endurance in patients with Parkinson's disease: A comparison with treadmill training.

PURPOSE: Cycle ergometer training improves gait in the elderly, but its effect in patients with Parkinson's disease (PD) is not completely known. METHODS: Twenty-nine PD inpatients were randomized to treadmill (n = 13, PD-T) or cycle ergometer (n = 16, PD-C) training for 3 weeks, 1 hour/day. Outcome measures were distance travelled during the 6-min walking test (6MWT), spatio-temporal variables of gait assessed by baropodometry, the Timed Up and Go (TUG) duration, the balance score through the Mini-BESTest, and the score of the Unified Parkinson's Disease Rating Scale (UPDRS). RESULTS: Sex, age, body mass index, disease duration, Hoehn-Yahr staging, comorbidity and medication did not differ between groups. At end of training, ANCOVA showed significant improvement, of similar degree, in both groups for 6MWT, speed, step length and cadence of gait, TUG, Mini-BESTest and UPDRS. CONCLUSIONS: This pilot study shows that cycle ergometer training improves walking parameters and reduces clinical signs of PD, as much as treadmill training does. Gait velocity is accompanied by step lengthening, making the gait pattern close to that of healthy subjects. Cycle ergometer is a valid alternative to treadmill for improving gait in short term in patients with PD.

Effects of slow repetitive transcranial magnetic stimulation in patients with corticobasal syndrome.

Corticobasal syndrome is characterized by asymmetric cortical sensorimotor dysfunction and parkinsonism; an altered cortical excitability has been reported. We explored with transcranial magnetic stimulation the motor cortical excitability in corticobasal syndrome, and the effects of slow repetitive transcranial magnetic stimulation. With transcranial magnetic stimulation, we studied two corticobasal syndrome patients. We determined bilaterally from the first dorsal interosseous muscle: relaxed threshold, and contralateral and ipsilateral silent period. We also evaluated the contralateral silent period after active/sham slow repetitive transcranial magnetic stimulation on the most affected side. At T0 the silent period was bilaterally short. On the most affected side, active slow repetitive transcranial magnetic stimulation induced a short lasting prolongation of the contralateral silent period. In corticobasal syndrome, transcranial magnetic stimulation showed a reduction cortical inhibitory phenomenon potentially reversed transiently by slow repetitive transcranial magnetic stimulation.

Amyotrophic lateral sclerosis outcome measures and the role of albumin and creatinine: a population-based study.

IMPORTANCE: There is an urgent need to identify reliable biomarkers of amyotrophic lateral sclerosis (ALS) progression for clinical practice and pharmacological trials. OBJECTIVES: To correlate several hematological markers evaluated at diagnosis with ALS outcome in a population-based series of patients (discovery cohort) and replicate the findings in an independent validation cohort from an ALS tertiary center. DESIGN, SETTING, AND PARTICIPANTS: The discovery cohort included 712 patients with ALS from the Piemonte and Valle d'Aosta Register for Amyotrophic Lateral Sclerosis from January 1, 2007, to December 31, 2011. The validation cohort comprised 122 patients with ALS at different stages of disease consecutively seen at an ALS tertiary center between January 1, 2007, and January 1, 2009. MAIN OUTCOMES AND MEASURES: The following hematological factors were investigated and correlated with survival: total leukocytes, neutrophils, lymphocytes, monocytes, glucose, creatinine, uric acid, albumin, bilirubin, total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, creatine kinase, thyroid-stimulating hormones, and erythrocyte sedimentation rate; all analyses were performed separately by sex. The patient of the validation cohort also underwent bioelectrical impedance analysis for the calculation of fat-free mass. RESULT: Of the 712 patients in the examined period in Piemonte and Valle d'Aosta, 638 (89.6%) were included in the study. Only serum albumin (men: ≤ 4.3 vs >4.3 mg/dL, P < .001; women: ≤ 4.3 vs >4.3 mg/dL, P < .001) and creatinine levels (men: ≤ 0.82 vs >0.82 mg/dL, P = .004; women: ≤ 0.65 vs >0.05 mg/dL, P = .004) and lymphocyte count (men: ≤ 1700 vs >1700/µL, P = .04; women: ≤ 1700 vs >1700/µL, P = .02) were significantly associated with ALS outcome in both sexes with a dose-response effect (better survival with increasing levels). These findings were confirmed in the validation cohort. Multivariable analysis showed that serum albumin (men: hazard ratio [HR], 1.39; 95% CI, 1.05-1.90; P = .02; women: HR, 1.73; 95 % CI, 1.35-2.39; P = .001) and creatinine (men: HR, 1.47; 95% CI, 1.11-1.95; P = .007; women: HR, 1.49; 95% CI, 1.07-2.05; P = .02) were independent predictors of survival in both sexes; no other hematological factor was retained in the model. In patients with ALS, serum albumin was correlated with markers of inflammatory state while serum creatinine was correlated with fat-free mass, which is a marker of muscle mass. CONCLUSIONS AND RELEVANCE: In ALS, serum albumin and creatinine are independent markers of outcome in both sexes. Creatinine reflects the muscle waste whereas albumin is connected with inflammatory state. Both creatinine and albumin are reliable markers of the severity of clinical status in patients with ALS and can be used in defining prognosis at the time of diagnosis.