Prevalence and Characteristics of Metabolic Hyperferritinemia in a Population-Based Central-European Cohort.

BACKGROUND: Hyperferritinemia (HF) is a common finding and can be considered as metabolic HF (MHF) in combination with metabolic diseases. The definition of MHF was heterogenous until a consensus statement was published recently. Our aim was to apply the definition of MHF to provide data on the prevalence and characteristics of MHF in a Central-European cohort. METHODS: This study was a retrospective analysis of the Paracelsus 10,000 study, a population-based cohort study from the region of Salzburg, Austria. We included 8408 participants, aged 40-77. Participants with HF were divided into three categories according to their level of HF and evaluated for metabolic co-morbidities defined by the proposed criteria for MHF. RESULTS: HF was present in 13% (n = 1111) with a clear male preponderance (n = 771, 69% of HF). Within the HF group, 81% (n = 901) of subjects fulfilled the metabolic criteria and were defined as MHF, of which 75% (n = 674) were characterized by a major criterion. In the remaining HF cohort, 52% (n = 227 of 437) of subjects were classified as MHF after application of the minor criteria. CONCLUSION: HF is a common finding in the general middle-aged population and the majority of cases are classified as MHF. The new classification provides useful criteria for defining MHF.

Prevalence of Subclinical Cardiovascular Disease in Patients with Non-Alcoholic-Fatty Liver Disease: Analysis of the Paracelsus 10.000 Cohort Study.

BACKGROUND: In patients with non-alcoholic fatty liver disease (NAFLD) cardiovascular diseases are more often the cause of death than the liver disease itself. However, the prevalence of atherosclerotic manifestations in individuals with NAFLD is still uncertain. This study aimed to explore the association between NAFLD and coronary artery calcification (CAC) in a Central European population. METHODS: A total of 1,743 participants from the Paracelsus 10,000 study were included. The participants underwent CAC scoring and were assessed for fatty liver index (FLI), fibrosing non-alcoholic steatohepatitis Index (FNI) and fibrosis-4 index (FIB-4 score), which are indicators for steatosis and fibrosis. Multivariable logistic regression models were calculated. RESULTS: Results revealed an association between liver steatosis/fibrosis and CAC. A FLI > 60 was associated with higher odds of NAFLD (OR 3.38, 95% CI: 2.61-4.39, p < 0.01) and increased prevalence of CAC-Score >300 compared to FLI <30 (9% vs. 3%, p < 0.01), even after adjusting for traditional cardiometabolic risk factors. While the crude odds ratios of the FIB-4 scores ≥ 1.3 and FNI score were significantly associated with increased odds of CAC, they became non-significant after adjusting for age, sex, and MetS. CONCLUSION: This study reveals a significant association between NAFLD and CAC. The findings suggest that assessing liver fat and fibrosis could enhance assessment of cardiovascular risk, but further research is needed to determine whether hepatic fat plays an independent role in the development of atherosclerosis and whether targeting liver steatosis can mitigate vascular risk.

Relationships between education and non-alcoholic fatty liver disease.

INTRODUCTION: Individuals with lower levels of education are at a higher risk of developing various health conditions due to limited access to healthcare and unhealthy lifestyle choices. However, the association between non-alcoholic fatty liver disease (NAFLD) and educational level remains unclear. Therefore, the aim of this study was to investigate whether there is an independent relationship between NAFLD and educational level as a surrogate marker for socioeconomic status (SES). METHODS: This cross-sectional study included 8,727 participants from the Paracelsus 10,000 study. The association between NAFLD and educational level was assessed using multivariable logistic regression models and multivariable linear regression. The primary endpoints were NAFLD (FLI score > 60) and liver fibrosis (FIB-4 score > 1.29). Further subgroup analysis with liver stiffness measurement was done. RESULTS: In the study, NAFLD prevalence was 23% among participants with high education, 33% among intermediate, and 40% among those with low education (p<0.01). Importantly, a significantly reduced risk of NAFLD was observed in individuals with higher education, as indicated by an adjusted relative risk of 0.52 (p < 0.01). Furthermore, higher education level was associated with significantly lower odds of NAFLD and fibrosis. Additionally, a subgroup analysis revealed that higher liver stiffness measurements were independently associated with lower levels of education. CONCLUSION: The study's findings indicate that a lower education level increases the risk of NAFLD independent of confounding factors. Therefore, these findings highlight the potential impact of educational attainment on NAFLD risk and emphasize the need for targeted interventions in vulnerable populations.

The platelet transcriptome and proteome in Alzheimer's disease and aging: an exploratory cross-sectional study.

Introduction: Alzheimer's disease (AD) and aging are associated with platelet hyperactivity. However, the mechanisms underlying abnormal platelet function in AD and aging are yet poorly understood. Methods: To explore the molecular profile of AD and aged platelets, we investigated platelet activation (i.e., CD62P expression), proteome and transcriptome in AD patients, non-demented elderly, and young individuals as controls. Results: AD, aged and young individuals showed similar levels of platelet activation based on CD62P expression. However, AD and aged individuals had a proteomic signature suggestive of increased platelet activation compared with young controls. Transcriptomic profiling suggested the dysregulation of proteolytic machinery involved in regulating platelet function, particularly the ubiquitin-proteasome system in AD and autophagy in aging. The functional implication of these transcriptomic alterations remains unclear and requires further investigation. Discussion: Our data strengthen the evidence of enhanced platelet activation in aging and provide a first glimpse of the platelet transcriptomic changes occurring in AD.

Inverse Association between Educational Status and Coronary CT Calcium Scores: Should We Reflect This in Our ASCVD Risk Assumptions?

Education is not a factor included in most cardiovascular risk models, including SCORE2. However, higher education has been associated with lower cardiovascular morbidity and mortality. Using CACS as a proxy for ASCVD, we studied the association between CACS and educational status. Subjects, aged 40-69, from the Paracelsus 10,000 cohort, who underwent calcium scoring as part of screening for subclinical ASCVD, were classified into low, medium, and high educational status using the Generalized International Standard Classification of Education. CACS was dichotomised as either 0 or >0 for logistic regression modelling. Our analysis showed that higher educational status was associated with higher odds for 0 CACS (aOR 0.42; 95%CI 0.26-0.70; p = 0.001). However, there was no statistically significant association between the levels of total, HDL or LDL cholesterol and educational status, nor any statistical differences in HbA1c. SCORE2 did not differ between the three educational categories (4 ± 2% vs. 4 ± 3% vs. 4 ± 2%; p = 0.29). While our observations confirmed the relationship between increased educational status and lower ASCVD risk, the effect of educational status was not mediated via its impact on classical risk factors in our cohort. Thus, perhaps educational status should be taken into account to more accurately reflect individual risk in cardiovascular risk models.

Prospective evaluation of radiographic manifestations of tuberculosis in relationship with CD4 count in patients with HIV/AIDS.

A major risk factor to develop active tuberculosis (TB) is the infection with the human immunodeficiency virus (HIV). Chest radiography is the first-line imaging modality used to rule out TB. Coinfected individuals present often with atypical imaging patterns, due to the immunosuppression caused by the virus, making diagnosis difficult. In this prospective observational study 268 TB and HIV coinfected patients were included. During a follow-up period of 24 weeks, the predominant patterns on chest radiography were analyzed and compared to the cluster of differentiation 4 (CD4) count under antiretroviral and anti-TB therapy. Patients with low CD4 counts (<200 cells//µL) showed more often lymphadenopathy (62% vs 38%;P = .08) and a miliary pattern (64% vs 36%;P = .04) but less likely cavitation (32% vs 68%;P = .008) or consolidation (47% vs 63%;P = .002) compared to individuals with higher CD4 counts. Over the follow-up period, partial response to therapy was the most frequent radiological evolution (62%), mainly accompanied by an increase of CD4 cells (92%). Patients with a decrease in CD4 count mostly presented with a worsening in radiological findings (53%). Radiographic TB manifestation correlated with the immune status of patients coinfected with HIV. Low CD4 counts often showed atypical manifestation.

Sequencing patterns of ventilatory indices in less trained adults.

Submaximal ventilatory indices, i.e., point of optimal ventilatory efficiency (POE) and anaerobic threshold (AT), are valuable indicators to assess the metabolic and ventilatory response during cardiopulmonary exercise testing (CPET). The order in which the ventilatory indices occur (ventilatory indices sequencing pattern, VISP), may yield additional information for the interpretation of CPET results and for exercise intensity prescription. Therefore, we determined whether different VISP groups concerning POE and AT exist. Additionally, we analysed fat metabolism via the exercise intensity eliciting the highest fat oxidation rate (Fatmax) as a possible explanation for differences between VISP groups. 761 less trained adults (41-68 years) completed an incremental exercise test on a cycle ergometer until volitional exhaustion. The ventilatory indices were determined using automatic and visual detection methods, and Fatmax was determined using indirect calorimetry. Our study identified two VISP groups with a lower work rate at POE compared to AT in VISPPOE < AT but not in group VISPPOE = AT. Therefore, training prescription based on POE rather than AT would result in different exercise intensity recommendations in 66% of the study participants and consequently in unintended physiological adaptions. VISPPOE < AT participants were not different to VISPPOE = AT participants concerning VO2peak and Fatmax. However, participants exhibiting a difference in work rate (VISPPOE < AT) were characterized by a higher aerobic capacity at submaximal work rate compared to VISPPOE = AT. Thus, analysing VISP may help to gain new insights into the complex ventilatory and metabolic response to exercise. But a methodological framework still must be established.

Neural mechanisms underlying the Rubber Hand Illusion: A systematic review of related neurophysiological studies.

INTRODUCTION: Many researchers took advantage of the well-established rubber hand illusion (RHI) paradigm to explore the link between the sense of body ownership and the different brain structures and networks. Here, we aimed to review the studies that have investigated this phenomenon by means of neurophysiological techniques. METHODS: The MEDLINE, accessed by Pubmed and EMBASE electronic databases, was searched using the medical subject headings: "Rubber hand illusion" AND "Transcranial magnetic stimulation (TMS)" OR "Evoked potentials (EP)" OR "Event related potentials (ERP)" OR "Electroencephalography (EEG)". RESULTS: Transcranial magnetic stimulation studies revealed a significant excitability drop in primary motor cortex hand circuits accompanying the disembodiment of the real hand during the RHI experience and that the perceived ownership over the rubber hand is associated with normal parietal-motor communication. Moreover, TMS provided causal evidence that the extrastriate body area is involved in the RHI and subsequently in body representation, while neuromodulation of ventral premotor area and the inferior parietal lobe did not result in an enhancement of embodiment. EP and ERP studies suggest that pre-existing body representations may affect larger stages of tactile processing and support predictive coding models of the functional architecture of multisensory integration in bodily perceptual experience. High-frequency oscillations on EEG play a role in the integrative processing of stimuli across modalities, and EEG activity in γ band activity in the parietal area reflects the visuotactile integration process. EEG studies also revealed that RHI is associated with the neural circuits underlying motor control and that premotor areas play a crucial role in mediating illusory body ownership. CONCLUSION: Neurophysiological studies shed new light on our understanding of the different aspects that contribute to the formation of a coherent self-awareness in humans.

Connectivity Analysis during Rubber Hand Illusion-A Pilot TMS-EEG Study in a Patient with SCI.

Background: Bodily self-perception is an important concept for several neurological disorders, including spinal cord injury (SCI). Changing one's bodily self-perception, e.g., via rubber hand illusion (RHI), induces alterations of bottom-up and top-down pathways and with this the connectivity between involved brain areas. We aim to examine whether (1) this process can be manipulated by changing cortical excitability, (2) connectivity between relevant brain areas differ when the RHI cannot be evoked, and (3) how this projection differs in a patient with SCI. Method: We applied RHI and facilitatory theta burst stimulation (TBS) on the right primary somatosensory cortex (S1) of 18 healthy participants and one patient with incomplete, cervical SCI. During RHI, we recorded high-density electroencephalography (HD-EEG) and extracted directed and nondirected connectivity measures. Results: There is no difference in connectivity between sham and real TBS or in the effectivity of RHI. We observed a higher laterality in the patient, i.e., higher connectivity of the right and lower of the left hemisphere. Besides this, connectivity patterns do not differ between healthy participants and the patient. Conclusion: This connectivity pattern might represent a neuroplastic response in the attempt to overcome the functional impairment of the patient resulting in a similar overall connectivity pattern to the healthy participants, yet with a higher sensitivity towards RHI and a higher laterality. The cortico-cortical communication was not altered depending on whether the illusion was provoked or not; hence, the perceptory illusion could not be observed in the EEG analysis.

Altered response to repetitive transcranial magnetic stimulation in patients with chronic primary insomnia.

BACKGROUND: We aimed at evaluating the amplitude changes of the motor evoked potentials (MEPs) induced by of low-frequency (LF) repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (M1) in10 patients with primary insomnia (PI) and in 10 age-matched healthy controls. METHODS: Median peak-to-peak MEP amplitudes were assessed in all subjects at three times: at baseline (T0), after the first train of a single rTMS session (T1), and after the whole rTMS procedure (T2). This consists of 20 trains of 1 Hz stimulation with 50 stimuli per train and an intertrain interval of 30 s. RESULTS: Resting motor threshold (RMT) and MEPs amplitude did not differ between the two groups at T0. A reduction of MEP size was observed at both T1 and T2 in all subjects, but this was significantly less pronounced in patients than in control subjects. CONCLUSIONS: The lack of MEP inhibition reflects an altered response to LF rTMS in patients with PI. These rTMS findings are indicative of an altered cortical plasticity in inhibitory circuits within M1 in PI. Subjects with PI exhibited an impairment of the LTD-like mechanisms induced by inhibitory rTMS, thus providing further support to the involvement of GABA neurotransmission in the pathophysiology of PI.

Functional Magnetic Resonance Imaging in the Final Stage of Creutzfeldt-Jakob Disease.

Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare fatal degenerative disease of the central nervous system. The clinical course is characterized by rapid progression of neurological and neuromuscular symptoms. The late stage with loss of consciousness is not well characterized. We report a 62-year-old male patient with sCJD with the clinical picture of a vegetative state/apallic syndrome, in whom we studied cortical responses using a vibration paradigm. The functional magnetic resonance imaging (fMRI) investigation demonstrated a clear response within the sensorimotor cortex, the cerebellum, the parietal cortex, the insular, and frontal inferior region. The finding of persistent cortical activity on fMRI in a patient with CJD in a state of unconsciousness has implications for the clinical management and for ethical considerations.

Effects of Rubber Hand Illusion and Excitatory Theta Burst Stimulation on Tactile Sensation: A Pilot Study.

Synchronous visuotactile stimulation on the own hidden hand and a visible fake limb can alter bodily self-perception and influence spontaneous neuroplasticity. The rubber hand illusion (RHI) paradigm experimentally produces an illusion of rubber hand ownership and arm shift by simultaneously stroking a rubber hand in view and a participant's visually occluded hand. The aim of this cross-over, placebo-controlled, single-blind study was to assess whether RHI, in combination with high-frequency repetitive transcranial magnetic stimulation (rTMS) given as intermittent (excitatory) theta burst stimulation (iTBS) applied over the hand area of the primary sensory region (S1) can enhance tactile sensation in a group of 21 healthy subjects and one patient with cervical spinal cord injury. Four sessions covered all combinations of real and sham stimulations of the RHI and the TBS: real TBS and real RHI, real TBS and sham RHI, sham TBS and real RHI, and both conditions sham. The condition sham TBS and real RHI shows the greatest effect on the proprioceptive drift (median 2.3 cm, IQR 2) and on the score of RHI questionnaires (median 3, IQR 2) in the control group as well as in the real-real condition (median 2, IQR 2). The sham TBS and real RHI condition also shows the best results in the electrical perception test of the patient (median 1.9 mA). Conversely, the upregulation of the cortical excitability of S1 via TBS seems to impair the effect of the RHI. This might be due to a strengthening of the top-down connection between the central nervous system and the periphery, diminishing the RHI. This finding helps in understanding the mechanisms of top-down and bottom-up mechanisms in healthy subjects and patients with spinal cord injury. The RHI paradigm could represent an interesting therapeutic approach in improving tactile sensation and rTMS techniques could modulate these effects. Yet, further studies are needed, to examine the direction of the interaction effect of TMS and RH.

Usefulness of EEG Techniques in Distinguishing Frontotemporal Dementia from Alzheimer's Disease and Other Dementias.

The clinical distinction of frontotemporal dementia (FTD) and Alzheimer's disease (AD) may be difficult. In this narrative review we summarize and discuss the most relevant electroencephalography (EEG) studies which have been applied to demented patients with the aim of distinguishing the various types of cognitive impairment. EEG studies revealed that patients at an early stage of FTD or AD displayed different patterns in the cortical localization of oscillatory activity across different frequency bands and in functional connectivity. Both classical EEG spectral analysis and EEG topography analysis are able to differentiate the different dementias at group level. The combination of standardized low-resolution brain electromagnetic tomography (sLORETA) and power parameters seems to improve the sensitivity, but spectral and connectivity biomarkers able to differentiate single patients have not yet been identified. The promising EEG findings should be replicated in larger studies, but could represent an additional useful, noninvasive, and reproducible diagnostic tool for clinical practice.

Abnormal cortical neuroplasticity induced by paired associative stimulation after traumatic spinal cord injury: A preliminary study.

We aimed at assessing in this pilot study whether patients with spinal cord injury (SCI) show alterations of sensorimotor plasticity within the primary motor cortex (M1). Since learning in human M1 occurs through LTP-like mechanisms, we employed the paired associative stimulation (PAS) protocol by transcranial magnetic stimulation (TMS), which is able to induce LTP-like effects in M1, in subjects with chronic SCI. We found that PAS protocol significantly increased corticospinal excitability as long as 30min in healthy subjects and in SCI patients with good motor recovery, while it was followed by a non-significant increase of MEP amplitude in the SCI patients with poor functional recovery. These findings suggest that the level of LTP-like phenomena is correlated with long term recovery and support the correlation between the ability of inducing excitability changes using TMS and the process of motor recovery. Increased cortical plasticity might imply greater capability for neuromodulation.

Effects of intermittent theta burst stimulation on spasticity after spinal cord injury.

PURPOSE: Spasticity is a common disorder in patients with spinal cord injury (SCI). The aim of this study was to investigate whether intermittent theta burst stimulation (iTBS), a safe, non-invasive and well-tolerated protocol of excitatory repetitive transcranial magnetic stimulation (rTMS), is effective in modulating spasticity in SCI patients. METHODS: In this randomized, double-blind, crossover, sham-controlled study, ten subjects with incomplete cervical or thoracic SCI received 10 days of daily sessions of real or sham iTBS. The H/M amplitude ratio of the Soleus H reflex, the amplitude of the motor evoked potentials (MEPs) at rest and during background contraction, as well as Modified Ashworth Scale (MAS) and the Spinal Cord Injury Assessment Tool for Spasticity (SCAT) were compared before and after the stimulation protocols. RESULTS: Patients receiving real iTBS showed significant increased resting and active MEPs amplitude and a significant reduction of the H/M amplitude ratio. In these patients also the MAS and SCAT scores were significantly reduced after treatment. These changes persisted up to 1 week after the end of the iTBS treatment, and were not observed under the sham-TBS condition. CONCLUSION: These findings suggest that iTBS may be a promising therapeutic tool for the spasticity in SCI patients.

Passive cycling in neurorehabilitation after spinal cord injury: A review.

CONTEXT/OBJECTIVE: Passive cycling (PC) may represent a potential alternative neurorehabilitation program for patients who are too weak or medically unstable to repeatedly practice active movements. We review here the most important animal and human studies addressing PC after spinal cord injury (SCI). METHODS: A MEDLINE search was performed using following terms: "passive", "cycling", "pedaling", "pedalling","spinal cord injury". RESULTS: Experimental studies revealed that PC modulated spinal reflex and reduced spasticity. PC also reduced autonomic dysreflexia and elicited cardio-protective effects. Increased levels of mRNA for brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor and neurotrophin-4 were found. In contrast, human studies failed to show an effect of PC on spasticity reduction and did not support its application for prevention of cardiovascular disease-related secondary complications. CONCLUSION: Available evidence to support the use of PC as standard treatment in patients with SCI is still rather limited. Since it is conceivable that PC motion could elicit sensory inputs to activate cortical structures and induce cortical plasticity changes leading to improved lower limb motor performance, further carefully designed prospective studies in subjects with SCI are needed.

Intracortical inhibitory and excitatory circuits in subjects with minimal hepatic encephalopathy: a TMS study.

Minimal hepatic encephalopathy (MHE) is the earliest form of hepatic encephalopathy (HE) and affects up to 80 % of patients with liver cirrhosis. By definition, MHE is characterized by psychomotor slowing and subtle cognitive deficits,  but obvious clinical manifestations are lacking. Given its covert nature, MHE is often underdiagnosed. This study was aimed at detecting neurophysiological changes, as assessed by means of transcranial magnetic stimulation (TMS), involved in the early pathogenesis of the HE. We investigated motor cortex excitability in 15 patients with MHE and in 15 age-matched age-matched cirrhotic patients without MHE; the resting motor threshold, the short-interval intracortical inhibition (SICI) and the intracortical facilitation (ICF) were examined. Paired-pulse TMS revealed significant increased SICI and reduced ICF in the patients with MHE. These findings may reflect abnormalities in intrinsic brain activity and altered organization of functional connectivity networks. In particular, the results suggest a shift in the balance between intracortical inhibitory and excitatory mechanisms towards a net increase of inhibitory neurotransmission. Together with other neurophysiological (in particular EEG) and neuroimaging techniques, TMS may thus provide early markers of cerebral dysfunction in cirrhotic patients with MHE.

Modulation of non-painful phantom sensation in subjects with spinal cord injury by means of rTMS.

We aimed in this study to investigate whether repetitive transcranial magnetic stimulation (rTMS), given as theta burst stimulation (TBS), can interfere with non-painful phantom sensations in subjects with spinal cord injury (SCI). In double-blind, sham-controlled experiments in five subjects with cervical or thoracic traumatic SCI, we evaluated the effects of a single session of inhibitory (continuous) TBS, excitatory (intermittent) TBS, or placebo TBS, on simplex and complex non-painful phantom sensations. The interventions targeted the contralateral primary motor cortex (M1), the primary sensory cortex (S1) and the posterior parietal cortex (PPC). Measurements were carried out at baseline (T0), 5 min (T1) and 30 min later (T2) after the intervention. Descriptive evaluation of results shows that non-painful phantom sensations were not affected by rTMS applied over M1. Continuous (inhibitory) TBS over S1 induced a short-lasting decrease of simple non-painful phantom sensations, while continuous TBS over PPC induced a short-lasting decrease of both simple and complex phantom sensations. Intermittent (excitatory) TBS over PPC induced a slight increase of non-painful phantom sensations. Tests for significance confirm these observations, but must be interpreted with caution because of the small sample size. In conclusion, non-painful phantom sensations may be associated to a hyperexcitability of PPC and to a lesser extent of S1, which can be normalized by inhibitory rTMS. Our preliminary findings provide further evidence that neuromodulatory techniques are able to reverse phantom sensations not only after limb amputation but also in other conditions characterized by deafferentation such as SCI.

Noninvasive Spinal Cord Stimulation: Technical Aspects and Therapeutic Applications.

BACKGROUND: Electrical and magnetic trans-spinal stimulation can be used to increase the motor output of multiple spinal segments and modulate cortico-spinal excitability. The application of direct current through the scalp as well as repetitive transcranial magnetic stimulation are known to influence brain excitability, and hence can also modulate other central nervous system structures, including spinal cord. OBJECTIVE: This study aimed to evaluate the effects and the therapeutic usefulness of these noninvasive neuromodulatory techniques in healthy subjects and in the neurorehabilitation of patients with spinal cord disorders, as well as to discuss the possible mechanisms of action. A comprehensive review that summarizes previous studies using noninvasive spinal cord stimulation is lacking. METHODS: PubMed (MEDLINE) and EMBASE were systematically searched to identify the most relevant published studies. We performed here an extensive review in this field. RESULTS: By decreasing the spinal reflex excitability, electrical and magnetic trans-spinal stimulation could be helpful in normalizing reflex hyperexcitability and treating hypertonia in subjects with lesions to upper motor neurons. Transcutaneous spinal direct current stimulation, based on applying direct current through the skin, influences the ascending and descending spinal pathways as well as spinal reflex excitability, and there is increasing evidence that it also can induce prolonged functional neuroplastic changes. When delivered repetitively, magnetic stimulation could also modulate spinal cord functions; however, at present only a few studies have documented spastic-reducing effects induced by repetitive spinal magnetic stimulation. Moreover, paired peripheral and transcranial stimulation can be used to target the spinal cord and may have potential for neuromodulation in spinal cord-injured subjects. CONCLUSIONS: Noninvasive electrical and magnetic spinal stimulation may provide reliable means to characterize important neurophysiologic and pathophysiologic aspects of spinal cord function. Moreover, transcutaneous direct current stimulation and repetitive magnetic stimulation may hold therapeutic promise in patients with spinal cord disorders, although future well-controlled studies are needed to corroborate and extend the preliminary findings.