Multimodal approaches supporting the diagnosis, prognosis and investigation of neural correlates of disorders of consciousness: A systematic review.

The limits of the standard, behaviour-based clinical assessment of patients with disorders of consciousness (DoC) prompted the employment of functional neuroimaging, neurometabolic, neurophysiological and neurostimulation techniques, to detect brain-based covert markers of awareness. However, uni-modal approaches, consisting in employing just one of those techniques, are usually not sufficient to provide an exhaustive exploration of the neural underpinnings of residual awareness. This systematic review aimed at collecting the evidence from studies employing a multimodal approach, that is, combining more instruments to complement DoC diagnosis, prognosis and better investigating their neural correlates. Following the PRISMA guidelines, records from PubMed, EMBASE and Scopus were screened to select peer-review original articles in which a multi-modal approach was used for the assessment of adult patients with a diagnosis of DoC. Ninety-two observational studies and 32 case reports or case series met the inclusion criteria. Results highlighted a diagnostic and prognostic advantage of multi-modal approaches that involve electroencephalography-based (EEG-based) measurements together with neuroimaging or neurometabolic data or with neurostimulation. Multimodal assessment deepened the knowledge on the neural networks underlying consciousness, by showing correlations between the integrity of the default mode network and the different clinical diagnosis of DoC. However, except for studies using transcranial magnetic stimulation combined with electroencephalography, the integration of more than one technique in most of the cases occurs without an a priori-designed multi-modal diagnostic approach. Our review supports the feasibility and underlines the advantages of a multimodal approach for the diagnosis, prognosis and for the investigation of neural correlates of DoCs.

Statistical Approaches to Identify Pairwise and High-Order Brain Functional Connectivity Signatures on a Single-Subject Basis.

Keeping up with the shift towards personalized neuroscience essentially requires the derivation of meaningful insights from individual brain signal recordings by analyzing the descriptive indexes of physio-pathological states through statistical methods that prioritize subject-specific differences under varying experimental conditions. Within this framework, the current study presents a methodology for assessing the value of the single-subject fingerprints of brain functional connectivity, assessed both by standard pairwise and novel high-order measures. Functional connectivity networks, which investigate the inter-relationships between pairs of brain regions, have long been a valuable tool for modeling the brain as a complex system. However, their usefulness is limited by their inability to detect high-order dependencies beyond pairwise correlations. In this study, by leveraging multivariate information theory, we confirm recent evidence suggesting that the brain contains a plethora of high-order, synergistic subsystems that would go unnoticed using a pairwise graph structure. The significance and variations across different conditions of functional pairwise and high-order interactions (HOIs) between groups of brain signals are statistically verified on an individual level through the utilization of surrogate and bootstrap data analyses. The approach is illustrated on the single-subject recordings of resting-state functional magnetic resonance imaging (rest-fMRI) signals acquired using a pediatric patient with hepatic encephalopathy associated with a portosystemic shunt and undergoing liver vascular shunt correction. Our results show that (i) the proposed single-subject analysis may have remarkable clinical relevance for subject-specific investigations and treatment planning, and (ii) the possibility of investigating brain connectivity and its post-treatment functional developments at a high-order level may be essential to fully capture the complexity and modalities of the recovery.

Cognitive outcomes in patients treated with neuromuscular electrical stimulation after coronary artery bypass grafting.

Objective: Mechanisms of neurocognitive injury as post-operative sequelae of coronary artery bypass grafting (CABG) are not understood. The systemic inflammatory response to surgical stress causes skeletal muscle impairment, and this is also worsened by immobility. Since evidence supports a link between muscle vitality and neuroprotection, there is a need to understand the mechanisms by which promotion of muscle activity counteracts the deleterious effects of surgery on long-term cognition. Methods: We performed a clinical trial to test the hypothesis that adding neuromuscular electrical stimulation (NMES) to standard rehabilitation care in post-CABG patients promotes the maintenance of skeletal muscle strength and the expression of circulating neuroprotective myokines. Results: We did not find higher serum levels of neuroprotective myokines, except for interleukin-6, nor better long-term cognitive performance in our intervention group. However, a greater increase in functional connectivity at brain magnetic resonance was seen between seed regions within the default mode, frontoparietal, salience, and sensorimotor networks in the NMES group. Regardless of the treatment protocol, patients with a Klotho increase 3 months after hospital discharge compared to baseline Klotho values showed better scores in delayed memory tests. Significance: We confirm the potential neuroprotective effect of Klotho in a clinical setting and for the first time post-CABG.

Telemedicine in Patients Affected by Chronic Liver Disease: A Scoping Review of Clinical Outcomes and the Devices Evaluated.

For patients with chronic liver disease (CLD), telemedicine is emerging as a useful tool to prevent liver decompensation or hospitalization, allowing access to and the decentralization of care, even for patients with limited resources. However, research and attendant evidence are still lacking; thus, this review aims to systematically explore the topic of telemonitoring for CLD to describe the currently used tools and clinical outcomes. The review was conducted by using key terms on PubMed/EMBASE and searching for observational studies or clinical trials (according to PRISMA recommendations) that were published between 6 April 2013 and 6 April 2023 to keep the technological framework limited to the last 10 years. The studies were described and grouped according to the aim of telemonitoring, the underlying disease, and the tools adopted to achieve remote monitoring. A total of 32 articles met the inclusion criteria. Of these, 11 articles report the successful use of a telehealth program to support and improve access to care in the management of HCV-related cirrhosis, eight articles examine the efficacy of telemedicine for remote monitoring interventions to prevent or decrease the risk of decompensation in high-risk patients, and five articles examine improvements in the physical performance and quality of life of cirrhotic patients through telehealth rehabilitation programs. Four studies were completed during the recent COVID-19 pandemic. Telehealth has the potential to provide and expand treatment access and reduce barriers to care for the most disadvantaged patients and might be able to reduce the need for hospital readmission for CLD, though most practice to test feasibility is still in the pilot stage.

Incidence and Long-term Functional Outcome of Neurologic Disorders in Hospitalized Patients With COVID-19 Infected With Pre-Omicron Variants.

BACKGROUND AND OBJECTIVES: A variety of neurologic disorders have been reported as presentations or complications of coronavirus disease 2019 (COVID-19) infection. The objective of this study was to determine their incidence dynamics and long-term functional outcome. METHODS: The Neuro-COVID Italy study was a multicenter, observational, cohort study with ambispective recruitment and prospective follow-up. Consecutive hospitalized patients presenting new neurologic disorders associated with COVID-19 infection (neuro-COVID), independently from respiratory severity, were systematically screened and actively recruited by neurology specialists in 38 centers in Italy and the Republic of San Marino. The primary outcomes were incidence of neuro-COVID cases during the first 70 weeks of the pandemic (March 2020-June 2021) and long-term functional outcome at 6 months, categorized as full recovery, mild symptoms, disabling symptoms, or death. RESULTS: Among 52,759 hospitalized patients with COVID-19, 1,865 patients presenting 2,881 new neurologic disorders associated with COVID-19 infection (neuro-COVID) were recruited. The incidence of neuro-COVID cases significantly declined over time, comparing the first 3 pandemic waves (8.4%, 95% CI 7.9-8.9; 5.0%, 95% CI 4.7-5.3; 3.3%, 95% CI 3.0-3.6, respectively; p = 0.027). The most frequent neurologic disorders were acute encephalopathy (25.2%), hyposmia-hypogeusia (20.2%), acute ischemic stroke (18.4%), and cognitive impairment (13.7%). The onset of neurologic disorders was more common in the prodromic phase (44.3%) or during the acute respiratory illness (40.9%), except for cognitive impairment whose onset prevailed during recovery (48.4%). A good functional outcome was achieved by most patients with neuro-COVID (64.6%) during follow-up (median 6.7 months), and the proportion of good outcome increased throughout the study period (r = 0.29, 95% CI 0.05-0.50; p = 0.019). Mild residual symptoms were frequently reported (28.1%) while disabling symptoms were common only in stroke survivors (47.6%). DISCUSSION: Incidence of COVID-associated neurologic disorders decreased during the prevaccination phase of the pandemic. Long-term functional outcome was favorable in most neuro-COVID disorders, although mild symptoms commonly lasted more than 6 months after infection.

European Working Group on SARS-CoV-2: Current Understanding, Unknowns, and Recommendations on the Neurological Complications of COVID-19.

Background: The emergence of COVID-19 was rapidly followed by infection and the deaths of millions of people across the globe. With much of the research and scientific advancement rightly focused on reducing the burden of severe and critical acute COVID-19 infection, the long-term effects endured by those who survived the acute infection has been previously overlooked. Now, an appreciation for the post-COVID-19 condition, including its neurological manifestations, is growing, although there remain many unknowns regarding the etiology and risk factors of the condition, as well as how to effectively diagnose and treat it. Methods: Here, drawing upon the experiences and expertise of the clinicians and academics of the European working group on COVID-19, we have reviewed the current literature to provide a comprehensive overview of the neurological sequalae of the post-COVID-19 condition. Results: In this review, we provide a summary of the neurological symptoms associated with the post-COVID-19 condition, before discussing the possible mechanisms which may underly and manifest these symptoms. Following this, we explore the risk factors for developing neurological symptoms as a result of COVID-19 and the post-COVID-19 condition, as well as how COVID-19 infection may itself be a risk factor for the development of neurological disease in the future. Lastly, we evaluate how the post-COVID condition could be accurately diagnosed and effectively treated, including examples of the current guidelines, clinical outcomes, and tools that have been developed to aid in this process, as well as addressing the protection provided by COVID-19 vaccines against the post-COVID-19 condition. Conclusions: Overall, this review provides a comprehensive overview of the neurological sequalae of the post-COVID-19 condition. Impact statement With our understanding of the neurological complications of the post-COVID-19 condition currently lacking sufficient depth, this review aimed at highlighting the current knowns and unknowns of the post-COVID-19 condition. In this review, we draw upon the experiences and expertise of the clinicians and academics of the European working group on COVID-19, as well as explore the current published literature, to evaluate a range of topics associated with the neurological complications of the post-COVID-19 condition. As a result, we have provided a comprehensive review of the topic. The European Working Group on SARS-CoV-2 Many essential questions surrounding COVID-19 remain unanswered, including its neurological complications and associated sequalae. In this review, we aim at identifying the current gaps in our understanding of post-COVID-19 neurological sequalae and suggest how future studies should be undertaken to fill these gaps. This review will draw upon the current biological and mechanistic understanding of COVID-19 and post-COVID-19 complications to discuss the clinically relevant aspects associated with the neurological manifestations of post-COVID-19 syndrome. From our discussions, the following questions were considered highly relevant for contemplation.

Neurological Screening in Elderly Liver Transplantation Candidates: A Single Center Experience.

BACKGROUND: Cerebral small vessels disease (cSVD) is an age-related disorder and risk factor for stroke and cognitive/motor impairments. Neurological complications (NCs) are among the causes of adverse outcomes in older liver transplant recipients. This study sought to determine whether cSVD predicts acute NCs in over 65-year-old liver transplant patients. METHODS: Data were collected, from a retrospective medical chart review, of 22 deceased donor liver transplant recipients aged 65 years or older with a pre-operative brain magnetic resonance imaging (MRI). We used the Fazekas score (0-3) as a quantitative measurement of the vascular lesion load seen in the MRI. We analyzed all post-operative acute NCs occurring during the hospital stay and any other non-NC. RESULTS: cSVD was recognized in all patients. Neurological complications (NCs) occurred in 18.1% of patients with toxic-metabolic encephalopathy the most frequent diagnosis (13.64%). More severe cSVD was associated with seizures (p = 0.0362), longer hospital stay (p 0.0299), and disability (p 0.0134). In our elderly cohort, hepatic encephalopathy (HE) (p 0.0287) and ascites (p 0.0270) were predictors of NCs after liver transplantation. Ascites and/or variceal bleeding and severity of liver disease were associated with adverse post-operative outcomes. The small sample size limited the statistical analysis power. CONCLUSIONS: We present the preliminary data of a single-center retrospective study aimed at understanding the cSVD role on NCs and non-NCs after a liver transplantation in elderly patients. This would encourage a more appropriate multicenter prospective study that will definitely confirm if a neurological screening in old age liver transplant candidates is appropriate.

Resting-State Functional Connectome in Patients with Brain Tumors Before and After Surgical Resection.

PURPOSE: High-grade glioma surgery has evolved around the principal belief that a safe maximal tumor resection improves symptoms, quality of life, and survival. Mapping brain function has been recently improved by resting-state functional magnetic resonance imaging (rest-fMRI), a novel imaging technique that explores networks connectivity at "rest." METHODS: This prospective study analyzed 10 patients with high-grade glioma in whom rest-fMRI connectivity was assessed both in single-subject and in group analysis before and after surgery. Seed-based functional connectivity analysis was performed with CONN toolbox. Network identification focused on 8 major functional connectivity networks. A voxel-wise region of interest (ROI) to ROI correlation map to assess functional connectivity throughout the whole brain was computed from a priori seeds ROI in specific resting-state networks before and after surgical resection in each patient. RESULTS: Reliable topography of all 8 resting-state networks was successfully identified in each participant before surgical resection. Single-subject functional connectivity analysis showed functional disconnection for dorsal attention and salience networks, whereas the language network demonstrated functional connection either in the case of left temporal glioblastoma. Functional connectivity in group analysis showed wide variations of functional connectivity in the default mode, salience, and sensorimotor networks. However, salience and language networks, salience and default mode networks, and salience and sensorimotor networks showed a significant correlation (P uncorrected <0.0025; P false discovery rate <0.077) in comparison before and after surgery confirming non-disconnection of these networks. CONCLUSIONS: Resting-state fMRI can reliably detect common functional connectivity networks in patients with glioma and has the potential to anticipate network alterations after surgical resection.

Advanced magnetic resonance imaging of cortical laminar necrosis in patients with stroke.

PURPOSE: The aim of this study was to assess the novel advanced magnetic resonance imaging findings of acute stage cortical laminar necrosis developing after complicated cardiovascular or abdominal surgery. MATERIALS AND METHODS: This institutional review board-approved study included patients with postoperative stroke due to cortical laminar necrosis imaged with magnetic resonance in the acute stage. Brain magnetic resonance imaging examinations were obtained on a 3T magnetic resonance scanner within 48 hours of the neurological symptoms, including diffusion-weighted images (b value, 1000 s/mm2) and arterial spin labelling using a pseudo-continuous arterial spin labelling method in four patients. Conventional and advanced magnetic resonance images were analysed to assess the imaging features in acute stage cortical laminar necrosis. RESULTS: The final population consisted of 14 patients (seven men and seven women, mean age 61 years, range 32-79 years) diagnosed with stroke and acute phase cortical laminar necrosis. All the patients presented with cortical lesions showing restricted diffusion on diffusion-weighted images and hypointensity on the apparent diffusion coefficient map. Cortical hyperintensity on T2-weighted or fluid-attenuated inversion recovery images was found in three (21%) and six (43%) patients, respectively. Reduced perfusion was noted in three out of four patients imaged with arterial spin labelling, while in one case no corresponding perfusion abnormality was noted on the arterial spin labelling maps. Arterial spin labelling abnormalities were much more extensive than diffusion restriction in two patients, and they were associated with a poor outcome. CONCLUSION: Cortical hyperintense abnormalities on diffusion-weighted imaging may be the only sign of developing cortical laminar necrosis injury. The acquisition of arterial spin labelling helps to identify perfusion alterations and the extension of the ischaemic injury.

Resting-State Functional Magnetic Resonance Imaging for Brain Tumor Surgical Planning: Feasibility in Clinical Setting.

The aim of this study was to introduce resting-state functional magnetic resonance imaging (rest-fMRI) capability for brain tumor surgical planning. rest-fMRI is an emerging functional neuroimaging technique potentially able to provide new insights into brain physiology and to provide useful information regarding brain tumors in preoperative and postoperative settings. rest-fMRI evaluates low-frequency fluctuations in the blood oxygen level-dependent signal while the subject is at rest during magnetic resonance imaging examination. Multiple resting-state networks have been identified, including the somatosensory, language, and visual networks, which are of primary importance for surgical planning. We discuss the feasibility of rest-fMRI examination before and after surgical resection of brain tumors in routine clinical practice and the usefulness of the information obtained for surgical planning in brain tumor resection. rest-fMRI is particularly useful for patients who are unable to cooperate with the task-based paradigm, such as children or patients who are sedated, paretic, or aphasic. Although standardization and validation of rest-fMRI are still ongoing, this technique is feasible and valuable and can be implemented for routine clinical surgical planning.

Neurological complications after cardiac surgery: a retrospective case-control study of risk factors and outcome.

BACKGROUND: To evaluate incidence, risk factors, and outcomes of postoperative neurological complications in patients undergoing cardiac surgery. METHODS: A total of 2121 patients underwent cardiac surgery between August, 2008 and December, 2013; 91/2121 (4.3%) underwent brain computed tomography (70/91, 77%) or magnetic resonance imaging (21/91, 23%) scan because of major stroke (37/2121, 1.7%) and a spectrum of transient neurological episodes as well as transient ischemic attacks and delirium /psychosis/seizures (54/2121, 2.5%). The mean age was 65.3 ± 12.1 years and 60 (65.9%) were male. Variables were compared among study- and matched-patients (n = 113) without neurological deficits. RESULTS: A total of 37/2121 (1.7%) patients had imaging evidence of stroke. Radiological examinations were done 5.72 ± 3.6 days after surgery. Patients with and without imaging evidence of stroke had longer intensive care unit length of stay (LOS) (13.8 ± 14.7 and 12.9 ± 15 days vs. 5.7 ± 12.1 days, respectively (p < 0.001) and hospital LOS (53 ± 72.8 and 35.5 ± 29.8 days vs. 18.4 ± 29.2 days, respectively (p < 0.001) than the control group. The hospital mortality of patients with and without imaging evidence of stroke was higher than the control group (7/37 patients [19%], and 12/54 patients [22%] vs. 4/115 patients [3%], respectively (p < 0.001). Multivariate analysis showed that bilateral internal carotid artery stenosis of any grade (p < .001), and re-do operations (p = .013) increased the risk of postoperative neurological complications. CONCLUSIONS: Neurological complications after cardiac surgery increase hospitalization and mortality even in patients without radiologic evidence of stroke. Bilateral internal carotid artery stenosis of any grade, suggesting a diffuse patient propensity toward atherosclerosis, and re-do operations increase the risk of postoperative neurological complications.

Guillain-Barré syndrome after orthotopic liver transplantation: A clinical manifestation of immune reconstitution inflammatory syndrome?

Guillain-Barrè Syndrome, as part of the spectrum of dysimmune neuropathies, is unexpected to occur in immunocompromised hosts. We describe a clinical case of Guillain-Barrè syndrome, occurred a few weeks after a liver transplant, and we postulate that our case would satisfy all requirements to explain this peripheral nervous system complication as a clinical manifestation of an Immune reconstitution inflammatory syndrome. In this setting of liver transplantation, complicated by potentially multiple infective triggers, reduction of immunosuppression and reversal of pathogen-induced immunosuppression, through antimicrobial therapy, may have led to pro-inflammatory response. The pro-inflammatory pattern would have sustained the pathophysiologic mechanism of this immune neuropathy.

Brain-core temperature of patients before and after orthotopic liver transplantation assessed by DWI thermometry.

PURPOSE: To assess brain-core temperature of end-stage liver disease patients undergoing orthotopic liver transplantation (OLT) using a temperature measurement technique based on the apparent diffusion coefficient of the cerebrospinal fluid in the lateral ventricles. MATERIALS AND METHODS: The study group was composed of 19 patients with a model for end-stage liver disease (MELD) score of 23.7 who underwent MR imaging before and after OLT. MR imaging studies were performed with a 1.5T MR scanner. Brain-core temperature (T: °C) was calculated using the following equation from the apparent diffusion coefficient (D) of the cerebrospinal fluid in the lateral ventricles: [Formula: see text] measured with a DWI sequence (b value 1000 s/mm2). We compared brain-core temperature of all patients before and after OLT. RESULTS: Brain-core temperature measurements were successfully taken in all patients before and after OLT. The measured brain-core temperature mean ± standard deviation was 38.67 ± 1.76 °C before OLT and 38.60 ± 0.99 °C after OLT, showing no significant difference (P = 0.643). CONCLUSIONS: Brain-core temperature was stable in patients undergoing OLT. DWI thermometry may provide a supplementary brain biomarker to confirm that cerebral blood flow and metabolism are stable in patients undergoing OLT.

Assessment of cerebral microbleeds by susceptibility-weighted imaging at 3T in patients with end-stage organ failure.

PURPOSE: Cerebral microbleeds (CMBs) are small rounded lesions representing cerebral hemosiderin deposits surrounded by macrophages that results from previous microhemorrhages. The aim of this study was to review the distribution of cerebral microbleeds in patients with end-stage organ failure and their association with specific end-stage organ failure risk factors. MATERIALS AND METHODS: Between August 2015 and June 2017, we evaluated 15 patients, 9 males, and 6 females, (mean age 65.5 years). Patients population was subdivided into three groups according to the organ failure: (a) chronic kidney failure (n = 8), (b) restrictive cardiomyopathy undergoing heart transplantation (n = 1), and (c) end-stage liver failure undergoing liver transplantation (n = 6). The MR exams were performed on a 3T MR unit and the SWI sequence was used for the detection of CMBs. CMBs were subdivided in supratentorial lobar distributed, supratentorial non-lobar distributed, and infratentorial distributed. RESULTS: A total of 91 microbleeds were observed in 15 patients. Fifty-nine CMBs lesions (64.8%) had supratentorial lobar distribution, 17 CMBs lesions (18.8%) had supratentorial non-lobar distribution and the remaining 15 CMBs lesions (16.4%) were infratentorial distributed. An overall predominance of supratentorial multiple lobar localizations was found in all types of end-stage organ failure. The presence of CMBs was significantly correlated with age, hypertension, and specific end-stage organ failure risk factors (p < 0.001). CONCLUSIONS: CMBs are mostly founded in supratentorial lobar localization in end-stage organ failure. The improved detection of CMBs with SWI sequences may contribute to a more accurate identification of patients with cerebral risk factors to prevent complications during or after the organ transplantation.

Association between multiple sclerosis, cancer risk, and immunosuppressant treatment: a cohort study.

BACKGROUND: The association between multiple sclerosis (MS) and cancer has long been investigated with conflicting results. Several reports suggest an increased cancer risk among MS patients treated with immunosuppressant (IS) drugs. METHODS: We performed a cohort study including MS patients recruited at the Neurological Department of the University of Palermo. Mean follow-up period was ten years for the whole cohort. We calculated cancer incidence among patients treated with IS. Incidence rates were compared in the cohort by calculating the relative risk according to length and dose of exposure to IS. Cancer incidence among MS patients was compared to cancer incidence in the general population of Sicily in similar age groups. RESULTS: On an overall cohort of 531 MS patients (346 women and 185 men) exposed to IS, we estimated a crude incidence rate for cancer of 2.26% (2.02% in women, 2.7% in men). Cancer risk was higher compared to rates observed among an equal number of patients not exposed to IS, and to the risk in the general population in Sicily at similar age groups (adjusted HR: 11.05; CI 1.67-73.3; p = 0.013). CONCLUSION: The present study showed a higher cancer risk in MS patients associated only to previous IS exposure. Studies on long-term outcomes are essential to evaluate the possibility that treatment options that need to be considered for a long time-period may modify risk for life threatening diseases.

Neurological injuries and extracorporeal membrane oxygenation: the challenge of the new ECMO era.

Extracorporeal membrane oxygenation (ECMO) is a life-saving mechanical respiratory and/or circulatory support for potentially reversible severe heart or respiratory injury untreatable with conventional therapies. Thanks to the technical and management improvements the use of ECMO has increased dramatically in the last few years. Data in the literature show a progressive increase in the overall outcome. Considering the improving survival rate of patients on ECMO, and the catastrophic effect of neurological injuries in such patients, the topic of neurological damage during the ICU stay in ECMO is gaining importance. We present a case series of six neurological injuries that occurred in 1 year during the ECMO run or after the ECMO weaning. In each case the neurological complication had a dramatic effect: ranging from brain death to prolonged ICU stay and long term disability. This case series has an informative impact for the multidisciplinary teams treating ECMO patients because of its heterogeneity in pathogenesis and clinical manifestation: cerebral hemorrhage, ischemic stroke due to cerebral fat embolism, acute disseminated encephalomyelitis due to H1N1 Influenza. In our ECMO hub we started strict neurological monitoring involving intensivists, a neurologist and our radiology service, but neurological complications are still an insidious diagnosis and treatment. Considering several possible neurological injuries may help reduce delay in diagnosis and speed rehabilitation.

Thyroid autoimmunity and dysfunction in multiple sclerosis patients during long-term treatment with interferon beta or glatiramer acetate: an Italian multicenter study.

Few long-term follow-up data are available on thyroid dysfunction (TD) in multiple sclerosis (MS) patients treated with glatiramer acetate (GA) or with interferon-beta (IFNb). In a cohort of 787 relapsing-remitting MS (RRMS) patients whom were followed up for 8 years, we observed an increased prevalence of TD and thyroid autoimmunity (TA) within the first year of IFNb treatment, regardless of the dose or frequency of administration, while no change was observed with GA treatment. The increased prevalence of TD and TA within the first year of IFNb treatment suggested the need for close monitoring of thyroid function and autoimmunity, though only during the first year of IFNb treatment.