A Prospective Observational Study of Frailty in Geriatric Revitalization Aimed at Community-Dwelling Elderly.

(1) Background: The increasing life expectancy brings an increase in geriatric syndromes, specifically frailty. The literature shows that exercise is a key to preventing, or even reversing, frailty in community-dwelling populations. The main objective is to demonstrate how an intervention based on multicomponent exercise produces an improvement in frailty and pre-frailty in a community-dwelling population. (2) Methods: a prospective observational study of a multicomponent exercise program for geriatric revitalization with people aged over 65 holding Barthel Index scores equal to, or beyond, 90. The program was developed over 30 weeks, three times a week, in sessions lasting 45-50 min each. Frailty levels were registered by the Short Physical Performance Battery, FRAIL Questionnaire Screening Tool, and Timed "Up & Go" at the beginning of the program, 30 weeks later (at the end of the program), and following 13 weeks without training; (3) Results: 360 participants completed the program; a greater risk of frailty was found before the program started among older women living in urban areas, with a more elevated fat percentage, more baseline pathologies, and wider baseline medication use. Furthermore, heterogeneous results were observed both in training periods and in periods without physical activity. However, they are consistent over time and show improvement after training. They show a good correlation between TUG and SPPB; (4) Conclusions: A thirty-week multicomponent exercise program improves frailty and pre-frailty status in a community-dwelling population with no functional decline. Nevertheless, a lack of homogeneity is evident among the various tools used for measuring frailty over training periods and inactivity periods.

Is the Combination of Robot-Assisted Therapy and Transcranial Direct Current Stimulation Useful for Upper Limb Motor Recovery? A Systematic Review with Meta-Analysis.

Stroke is the third leading cause of disability in the world, and effective rehabilitation is needed to improve lost functionality post-stroke. In this regard, robot-assisted therapy (RAT) and transcranial direct current stimulation (tDCS) are promising rehabilitative approaches that have been shown to be effective in motor recovery. In the past decade, they have been combined to study whether their combination produces adjuvant and greater effects on stroke recovery. The aim of this study was to estimate the effectiveness of the combined use of RATs and tDCS in the motor recovery of the upper extremities after stroke. After reviewing 227 studies, we included nine randomised clinical trials (RCTs) in this study. We analysed the methodological quality of all nine RCTs in the meta-analysis. The analysed outcomes were deficit severity, hand dexterity, spasticity, and activity. The addition of tDCS to RAT produced a negligible additional benefit on the effects of upper limb function (SMD -0.09, 95% CI -0.31 to 0.12), hand dexterity (SMD 0.12, 95% CI -0.22 to 0.46), spasticity (SMD 0.04, 95% CI -0.24 to 0.32), and activity (SMD 0.66, 95% CI -1.82 to 3.14). There is no evidence of an additional effect when adding tDCS to RAT for upper limb recovery after stroke. Combining tDCS with RAT does not improve upper limb motor function, spasticity, and/or hand dexterity. Future research should focus on the use of RAT protocols in which the patient is given an active role, focusing on the intensity and dosage, and determining how certain variables influence the success of RAT.

Combining transcranial direct current stimulation with hand robotic rehabilitation in chronic stroke patients: a double blind randomized clinical trial.

OBJECTIVE: This study aimed to assess the impact of combining transcranial direct current stimulation (tDCS) with end-effector robot-assisted treatment (RAT) on upper limb function, spasticity, and hand dexterity in chronic stroke patients. DESIGN: This was a prospective, double-blind randomized trial with 20 equally allocated stroke patients. The experimental group received dual-tDCS (anode over affected M1, cathode over contralateral M1) alongside RAT, while the control group received sham tDCS with the same electrode placement + RAT. Each patient underwent 20 combined tDCS and RAT sessions. The primary outcome measure was the Fugl Meyer Upper Limb motor score (mFM-UL), with secondary outcomes including AMADEO® kinematic measures, Action Research Arm Test (ARAT), and Functional Independence Measure (FIM). Assessments were conducted at baseline, post-rehabilitation, and three months later. RESULTS: Combining bilateral tDCS with RAT did not yield additional improvements in mFM-UL, FIM, or ARAT scores among stroke patients. However, the real tDCS group showed enhanced finger flexion in the affected hand based on AMADEO® kinematic measures. CONCLUSION: The addition of tDCS to RAT did not result in significant overall functional improvements in chronic stroke patients. However, a benefit was observed in finger flexion of the affected hand.

Clinical outcome prediction of acute neurological patients admitted to the emergency department: Sequential Organ Failure Assessment score and modified SOFA score.

Background: The aim of this study was to determine the ability of the Sequential Organ Failure Assessment score (SOFA) and modified SOFA score (mSOFA) as predictive tools for 2-day and 28-day mortality and ICU admission in patients with acute neurological pathology treated in hospital emergency departments (EDs). Methods: An observational, prospective cohort study in adults with acute neurological disease transferred by ambulance to an ED was conducted from 1 January 2019 to 31 August 2022 in five hospitals in Castilla-León (Spain). Score discrimination was assessed by the area under the curve (AUC) of the receiver operating characteristic (ROC) curve of the score. Results: A total of 640 adult patients with neurological disease were included. For the prediction of 2-day mortality (all-cause), mSOFA presented a higher AUC than SOFA (mSOFA = 0.925 vs. SOFA = 0.902). This was not the case for 28-day mortality, for which SOFA was higher than mSOFA (mSOFA = 0.852 vs. SOFA = 0.875). Finally, ICU admission showed that SOFA was higher than mSOFA (mSOFA = 0.834 vs. SOFA = 0.845). Conclusion: Both mSOFA and SOFA presented similar predictive ability, with mSOFA being the best predictor for short-term mortality and SOFA being the best predictor for medium-term mortality, as well as for ICU admission. These results in a cohort of patients with acute neurological pathology pave the way for the use of both predictive tools in the ED. The inclusion of these tools could improve the clinical assessment and further treatment of neurological patients, who commonly present the worst outcomes.

"Nurses and health professionals facing female genital mutilation: a qualitative study ".

BACKGROUND: Transnational migratory movements make Spain a country with a very diverse population, including women and girls from countries where Female Genital Mutilation (FGM) is practiced. Given this reality, we set out to carry out a qualitative study to identify the knowledge, attitudes and skills of health professionals regarding FGM. METHOD: Qualitative study with a content analysis approach. Forty-seven health professionals with the profiles of Nursing, Family Medicine, Pediatrics, Midwifery and Gynecology and Obstetrics were purposively selected. Data were collected through semi-structured in-depth interviews and focus groups. The qualitative content analysis approach was used for data analysis. The study was conducted in the years 2019 and 2022. RESULTS: Although most professionals are aware of the current legislation on FGM in Spain, only a few of them are aware of the existence of the FGM prevention protocol in Castilla-La Mancha. This lack of knowledge together with the perception that FGM belongs to the private sphere of women, contributes to the loss of opportunities to identify and prevent FGM. CONCLUSION: Health professionals' training, especially midwives and pediatricians, is essential to the identification and action against Female Genital Mutilation.

Prehospital seizures: Short-term outcomes and risk stratification based in point-of-care testing.

BACKGROUND: Information for treatment or hospital derivation of prehospital seizures is limited, impairing patient condition and hindering patients risk assessment by the emergency medical services (EMS). This study aimed to determine the associated factors to clinical impairment, and secondarily, to determine risk factors associated to cumulative in-hospital mortality at 2, 7 and 30 days, in patients presenting prehospital seizures. METHODS: Prospective, multicentre, EMS-delivery study involving adult subjects with prehospital seizures, including five advanced life support units, 27 basic life support units and four emergency departments in Spain. All bedside variables: including demographic, standard vital signs, prehospital laboratory tests and presence of intoxication or traumatic brain injury (TBI), were analysed to construct a risk model using binary logistic regression and internal validation methods. RESULTS: A total of 517 patients were considered. Clinical impairment was present in 14.9%, and cumulative in-hospital mortality at 2, 7 and 30-days was 3.4%, 4.6% and 7.7%, respectively. The model for the clinical impairment indicated that respiratory rate, partial pressure of carbon dioxide, blood urea nitrogen, associated TBI or stroke were risk factors; higher Glasgow Coma Scale (GCS) scores mean a lower risk of impairment. Age, potassium, glucose, prehospital use of mechanical ventilation and concomitant stroke were risk factors associated to mortality; and oxygen saturation, a high score in GCS and haemoglobin were protective factors. CONCLUSION: Our study shows that prehospital variables could reflect the clinical impairment and mortality of patients suffering from seizures. The incorporation of such variables in the prehospital decision-making process could improve patient outcomes.

Modified Rapid Emergency Medicine Score-Lactate (mREMS-L) performance to screen non-anticipated 30-day-related-mortality in emergency department.

BACKGROUND: The aim of this study was to compare the ability to predict 30-day in-hospital mortality of lactate versus the modified Rapid Emergency Medicine Score (mREMS) versus the arithmetic sum of the mREMS plus the numerical value of lactate (mREMS-L). METHODS: A prospective, multicentric, emergency department delivery, pragmatic study was conducted. To determine the predictive capacity of the scales, lactate was measured and the mREMS and mREMS-L were calculated in adult patients (aged>18 years) transferred with high priority by ambulance to the emergency department in five hospitals of Castilla y Leon between 1 January 2020 and 31 December 2021. The area under the receiver operating characteristic (ROC) curve of each of the scales was calculated in terms of mortality for 30 days. RESULTS: A total of 5371 participants were included, and the in-hospital mortality rate at 30 days was of 11.4% (615 cases). The best cut-off point determined in the mREMS was 7.0 points (sensitivity of 67% and specificity of 84%), and for lactate, the cut-off point was 1.4 mmol/L (sensitivity of 88% and specificity of 67%). Finally, the combined mREMS-L showed a cut-off point of 7.9 (sensitivity of 83% and a specificity of 83%). The area under the ROC curve of the mREMS, lactate and mREMS-L for 30-day mortality was 0.851, 0.853, and 0.903, respectively (p < 0.001 in all cases). CONCLUSIONS: The new score generated, mREMS-L, obtained better statistical results than its components (mREMS and lactate) separately.

Hand Motor Fatigability Induced by a Simple Isometric Task in Spinal Cord Injury.

This study aimed: (1) to evaluate the hand motor fatigability in people with spinal cord injury (SCI) and compare it with measurements obtained form an able-bodied population; (2) to compare the hand motor fatigability in people with tetraplegia and in people with paraplegia; and (3) to analyse if motor fatigability is different in people with SCI with and without clinical significant perceived fatigability. MATERIALS AND METHODS: 96 participants with SCI (40 cervical and 56 thoracolumbar) and 63 able-bodied controls performed a simple hand isometric task to assess motor fatigability. The Fatigue Severity Scale was used for perceived fatigability evaluation. RESULTS: The main results of this study can be summarized as follows: (1) the waning in muscle force (motor fatigability) during a fatiguing task is similar in controls and participants with SCI; (2) the motor fatigability is influenced by the maximal muscle force (measured at the beginning of the task); and (3) the perceived fatigability and the motor fatigability are largely independent in the individuals with SCI. CONCLUSION: Our findings suggest that the capability to maintain a prolonged effort is preserved in SCI, and this capacity depends on the residual maximal muscle force in people with SCI.

Static magnetic field stimulation over motor cortex modulates resting functional connectivity in humans.

Focal application of transcranial static magnetic field stimulation (tSMS) over the human motor cortex induces local changes in cortical excitability. Whether tSMS can also induce distant network effects, and how these local and distant effects may vary over time, is currently unknown. In this study, we applied 10 min tSMS over the left motor cortex of healthy subjects using a real/sham parallel design. To measure tSMS effects at the sensori-motor network level, we used resting-state fMRI. Real tSMS, but not sham, reduced functional connectivity within the stimulated sensori-motor network. This effect of tSMS showed time-dependency, returning to sham levels after the first 5 min of fMRI scanning. With 10 min real tSMS over the motor cortex we did not observe effects in other functional networks examined (default mode and visual system networks). In conclusion, 10 min of tSMS over a location within the sensori-motor network reduces functional connectivity within the same functional network.

Comparison of Nine Early Warning Scores for Identification of Short-Term Mortality in Acute Neurological Disease in Emergency Department.

(1) Background: The aim was screening the performance of nine Early Warning Scores (EWS), to identify patients at high-risk of premature impairment and to detect intensive care unit (ICU) admissions, as well as to track the 2-, 7-, 14-, and 28-day mortality in a cohort of patients diagnosed with an acute neurological condition. (2) Methods: We conducted a prospective, longitudinal, observational study, calculating the EWS [Modified Early Warning Score (MEWS), National Early Warning Score (NEWS), VitalPAC Early Warning Score (ViEWS), Modified Rapid Emergency Medicine Score (MREMS), Early Warning Score (EWS), Hamilton Early Warning Score (HEWS), Standardised Early Warning Score (SEWS), WHO Prognostic Scored System (WPSS), and Rapid Acute Physiology Score (RAPS)] upon the arrival of patients to the emergency department. (3) Results: In all, 1160 patients were included: 808 patients were hospitalized, 199 cases (17%) required ICU care, and 6% of patients died (64 cases) within 2 days, which rose to 16% (183 cases) within 28 days. The highest area under the curve for predicting the need for ICU admissions was obtained by RAPS and MEWS. For predicting mortality, MREMS obtained the best scores for 2- and 28-day mortality. (4) Conclusions: This is the first study to explore whether several EWS accurately identify the risk of ICU admissions and mortality, at different time points, in patients with acute neurological disorders. Every score analyzed obtained good results, but it is suggested that the use of RAPS, MEWS, and MREMS should be preferred in the acute setting, for patients with neurological impairment.

Lactate improves the predictive ability of the National Early Warning Score 2 in the emergency department.

AIMS: The aim of this study was to compare the ability to predict 2-, 7-, 14-, and 30-day in-hospital mortality of lactate vs the National Early Warning Score 2 (NEWS2) vs the arithmetic sum of the NEWS2 plus the numerical value of lactate (NEWS2-L). METHODS: This was a prospective, multicentric, emergency department delivery, pragmatic cohort study. To determine the predictive capacity of lactate, we calculated the NEWS2 and NEWS2-L in adult patients (aged >18 years) transferred with high priority by ambulance to the emergency department in five hospitals of Castilla y Leon (Spain) between November 1, 2019, and September 30, 2020. The area under the receiver operating characteristic curve of each of the scales was calculated in terms of mortality for every time frame (2, 7, 14, and 30 days). We determined the cut-off point of each scale that offered highest sensitivity and specificity using the Youden index. RESULTS: A total of 1716 participants were included, and the in-hospital mortality rates at 2, 7, 14, and 30 days were of 7.8% (134 cases), 11.6% (200 cases), 14.2% (243 cases), and 17.2% (295 cases), respectively. The best cut-off point determined in the NEWS2 was 6.5 points (sensitivity of 97% and specificity of 59%), and for lactate, the cut-off point was 3.3 mmol/L (sensitivity of 79% and specificity of 72%). Finally, the combined NEWS2-L showed a cut-off point of 11.7 (sensitivity of 86% and a specificity of 85%). The area under the receiver operating characteristic curve of the NEWS2, lactate, and NEWS2-L in the validation cohort for 2-day mortality was 0.889, 0.856, and 0.923, respectively (p<0.001 in all cases). CONCLUSIONS: The new score generated, NEWS2-L, obtained better statistical results than its components (NEWS2 and lactate) separately.

COVID-19 as a risk factor for long-term mortality in patients managed by the emergency medical system: A prospective, multicenter, ambulance-based cohort study.

Introduction: COVID-19 has initially been studied in terms of an acute-phase disease, although recently more attention has been given to the long-term consequences. In this study, we examined COVID-19 as an independent risk factor for long-term mortality in patients with acute illness treated by EMS (emergency medical services) who have previously had the disease against those who have not had the disease. Methods: A prospective, multicenter, ambulance-based, ongoing study was performed with adult patients with acute disease managed by EMS and transferred with high priority to the emergency department (ED) as study subjects. The study involved six advanced life support units, 38 basic life support units, and five emergency departments from Spain. Sociodemographic inputs, baseline vital signs, pre-hospital blood tests, and comorbidities, including COVID-19, were collected. The main outcome was long-term mortality, which was classified into 1-year all-cause mortality and 1-year in- and out-of-hospital mortality. To compare both the patients with COVID-19 vs. patients without COVID-19 and to compare survival vs non-survival, two main statistical analyses were performed, namely, a longitudinal analysis (Cox regression) and a logistic regression analysis. Results: Between 12 March 2020 and 30 September 2021, a total of 3,107 patients were included in the study, with 2,594 patients without COVID-19 and 513 patients previously suffering from COVID-19. The mortality rate was higher in patients with COVID-19 than in patients without COVID-19 (31.8 vs. 17.9%). A logistic regression showed that patients previously diagnosed with COVID-19 presented higher rates of nursing home residency, a higher number of breaths per minute, and suffering from connective disease, dementia, and congestive heart failure. The longitudinal analysis showed that COVID-19 was a risk factor for mortality [hazard ratio 1.33 (1.10-1.61); p < 0.001]. Conclusion: The COVID-19 group presented an almost double mortality rate compared with the non-COVID-19 group. The final model adjusted for confusion factors suggested that COVID-19 was a risk factor for long-term mortality.

Female Genital Mutilation: Knowledge and Skills of Health Professionals.

BACKGROUND: Female genital mutilation (FGM) is any process that injures female genitals for non-medical reasons and is a violation of women's human rights. An important number of women from countries where FGM is performed are arriving to Western countries. Health professionals are important for detecting cases of FGM. No surveys to assess knowledge, attitudes and practices on FGM among healthcare professionals has been conducted in Castilla la Mancha (Spain) until now. METHODS: The main goal of the study is assessing knowledge, attitudes and perceptions of healthcare professionals in relation to FGM. A cross-sectional descriptive study was conducted based on self-administered online surveys to nurses, midwives, family doctors, pediatricians, obstetrics and gynecologists. RESULTS: In total, 1168 professionals answered the surveys. Just 13.9% indicated that they had received training in FGM, however just 10.7% correctly identified the three types of FGM, 10.7% the countries where it is usually practiced, 33.9% knew the legislation in Spain and only 4.4% found a case of FGM during their professional practice. Regarding the knowledge about protocols, 8.64% of the sample indicated to know one of them. CONCLUSION: The present study demonstrate that it is necessary to improve the training and awareness of healthcare professionals related to FGM in Castilla la Mancha.

Neuropsychological Study in Patients with Spinal Cord Injuries.

The present investigation was designed to determinate the nature, pattern, and extent of cognitive deficits in a group of participants with subacute and chronic spinal cord injury (SCI). METHODS: A cross-sectional study was conducted in both patients with subacute and chronic SCI. Different cognitive functions were evaluated through a neuropsychological protocol designed for this purpose, taking into account the patient's emotional state. RESULTS: A total of 100 patients suffering a spinal cord injury were evaluated. There were no differences between the two groups when age, sex, level of education, and region of origin were studied. The chronic injured patients obtained lower scores in the neuropsychological evaluation protocol respective to the subacute injured patients. CONCLUSIONS: Subjects with chronic spinal cord injury presented a cognitive profile that differed greatly in the number of altered cognitive functions as well as in their magnitude from the subacute spinal cord injured patient profile. Moreover, cognitive dysfunction may be important beyond the end of the first stage of rehabilitation as it can affect an individual's quality of life and possible integration in society.

Facilitating Factors of Professional Health Practice Regarding Female Genital Mutilation: A Qualitative Study.

Introduction: According to figures released by UNICEF (United Nations Children's Fund), more than 200 million girls and women have suffered female genital mutilation (FGM) in 30 African and Middle East countries. An increasing number of African women who come from ethnic groups where FGM is practised are arriving in Western countries. Healthcare professionals play a fundamental role in its prevention. Goals: To learn about the factors that healthcare professionals consider as facilitators for prevention and action when faced with female genital mutilation. Methods: A cross-sectional descriptive study developed on the basis of the qualitative methodological perspective, where 43 healthcare professionals participated. A series of analysis dimensions were established, based on which, the interview and discussion group scripts were designed. Results: Addressing FGM requires a series of structural adaptations of the healthcare system that facilitate the recording and monitoring of cases, both for treatment and for prevention. In addition, it is necessary to establish coordination between the healthcare, social services and education sectors. Conclusions: The existence of a protocol of action and training in its use is one of the key tools to take into account.

Effects of fatigue induced by repetitive movements and isometric tasks on reaction time.

PURPOSE: The understanding of fatigue of the human motor system is important in the fields of ergonomics, sport, rehabilitation and neurology. In order to understand the interactions between fatigue and reaction time, we evaluated the effects of two different fatiguing tasks on reaction time. METHODS: 83 healthy subjects were included in a case-control study with three arms where single and double choice reaction time tasks were performed before and after 2 min fatiguing task (an isometric task, a finger tapping task and at rest). RESULTS: After an isometric task, the right-fatigued hand was slower in the choice component of a double choice reaction time task (calculated as the individual difference between single and double choice reaction times); also, the subjects that felt more fatigued had slower choice reaction time respect to the baseline assessment. Moreover, in relationship to the performance decay after two minutes, finger tapping task produces more intense fatigability perception. CONCLUSIONS: We confirmed that two minutes of isometric or repetitive tasks are enough to produce fatigue. The fatigue perception is more intense for finger tapping tasks in relation to the performance decay. We therefore confirmed that the two fatiguing tasks produced two different kind of fatigue demonstrating that with a very simple protocol it is possible to test subjects or patients to quantify different form of fatigue.

Physiological Response of Quality Cardiopulmonary Resuscitation, Crossover Trial on Mannequin in Extreme Temperature Conditions.

BACKGROUND: To determine the relationship between physiological fatigue and the quality of cardiopulmonary resuscitation (CPR) in trained resuscitators in hostile thermal environments (extreme cold and heat) simulating the different conditions found in an out-of-hospital cardiorespiratory arrest. METHODS: Prospective observational study involving 60 students of the health sciences with training in resuscitation, who simulated CPR on a mannequin for 10 min in different thermal environments: thermo-neutral environment (21 °C and 60% humidity), heat environment (41 °C and 98% humidity) and cold environment (-35 °C and 80% humidity). Physiological parameters (heart rate and lactic acid) and CPR quality were monitored. RESULTS: We detected a significant increase in the number of compressions per minute in the "heat environment" group after three minutes and in the mean rate after one minute. We observed a negative correlation between the total number of compressions and mean rate with respect to mean depth. The fraction of compressions (proportion of time in which chest compressions are carried out) was significant over time and the mean rate was higher in the "heat environment". Physiological parameters revealed no differences in heart rate depending on the resuscitation scenario; however, there was a greater and faster increase in lactate in the "heat environment" (significant at minute 3). The total proportion of participants reaching metabolic fatigue was also higher in the "heat environment". CONCLUSIONS: A warm climate modifies metabolic parameters, reducing the quality of the CPR maneuver.

Development of chronic pain in males with traumatic spinal cord injury: role of circulating levels of the chemokines CCL2 and CXCL10 in subacute stage.

STUDY DESIGN: Longitudinal study. OBJECTIVES: To assess the impact of spinal cord injury (SCI) on circulating levels of chemokines (CCL2 and CXCL10) and its relation with pain development. SETTING: National Hospital for SCI patients. METHODS: We longitudinally studied changes in the circulating levels of CCL2 and CXCL10 in 27 male patients with complete SCI who were evaluated in the early subacute phase and indeed 3 and 6 months after injury measuring at each time-point serum levels of CCL2 and CXCL10. Patients were telephonically interviewed about pain 1 year after SCI. RESULTS: In the early subacute phase, patients with pain showed higher CXCL10 and similar CCL2 levels as opposed to those without pain. Moreover, CCL2 concentrations were positively associated with pain intensity. The results obtained by analysing the temporal profile of the chemokines suggested that CXCL10 was inclined to decrease over time, while CCL2 increased over time. CONCLUSION: The results of this preliminary study, the first performed in humans with traumatic SCI, suggest a link between changes in the circulating chemokine profile and pain development in subacute SCI stage as well as with severity in a more chronic stage. Large series studies will evaluate whether the circulating chemokine status can be useful as a biomarker for assessing the patients' risk for pain development.

Fatigue in Multiple Sclerosis: General and Perceived Fatigue Does Not Depend on Corticospinal Tract Dysfunction.

Background: Multiple sclerosis (MS) is an autoimmune disorder of the CNS in which inflammation, demyelination, and axonal damage of the central nervous system coexist. Fatigue is one of the most disabling symptoms in MS and little is known about the neurophysiological mechanisms involved. Methods: To give more mechanistic insight of fatigue in MS, we studied a cohort of 17 MS patients and a group of 16 age-matched healthy controls. Baseline Fatigue Severity Scales and Fatigue Rating were obtained from both groups to check the level of fatigue and to perform statistical correlations with fatigue-induced neurophysiologic changes. To induce fatigue we used a handgrip task. During the fatiguing task, we evaluated fatigue state (using a dynamometer) and after the task we evaluated the Borg Rating of Perceived Exertion Scale. Transcranial magnetic stimulation and peripheral electric stimulation were used to assess corticospinal tract and peripheral system functions before and after the task. Results: Clinically significant fatigue and central motor conduction time were greater in patients than in controls, while motor cortex excitability was decreased and maximal handgrip strength reduced in patients. Interestingly, fatigue state was positively correlated to perceived fatigue in controls but not in patients. Furthermore, in the presence of similar fatigue state over time, controls showed a significant fatigue-related reduction in motor evoked potential (a putative marker of central fatigue) whereas this effect was not seen in patients. Conclusions: in MS patients the pathogenesis of fatigue seems not driven by the mechanisms directly related to corticospinal function (that characterize fatigue in controls) but seems probably due to other "central abnormalities" upstream to primary motor cortex.