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Background: Despite the frequent use of the Timed Up and Go (TUG) test in clinical trials, evaluation of longitudinal test-retest reliability is generally lacking and still inconclusive for patients with Parkinson’s disease (PD). Objective: We aimed to further investigate long-term reliability and sensitivity of the TUG test among this population. Furthermore, we explored alternative assessment strategies of the test aimed at elucidating whether the inclusion or combination of timed trials may have potential implications on outcome measure. Methods: Relative and absolute reliability of the TUG performance were obtained in forty-three subjects with PD over three timed trials in two different testing sessions separated by a two-months period. Results: Our results reported excellent intra-session and moderate inter-session reliability coefficients. The use of different assessment strategies of the TUG was found to have an important impact on outcome measure, highlighting the averaging of several timed trials in each testing session as a recommended alternative to minimize measurement error and increase reliability in longitudinal assessments. Nevertheless, beyond acceptable reliability, poor trial-to-trial stability of the measure appears to exist, since the ranges of expected variability upon retesting were wide and the incidence of spurious statistical effects was not negligible, especially in longitudinal repeated testing. Conclusion: Limitations may exist in the interpretation of the TUG outputs as part of longitudinal assessments aimed at evaluating treatment effectiveness in PD population. Researchers and practitioners should be aware of these concerns to prevent possible misrepresentations of functional ability in patients for a particular intervention.

Objective To evaluate the relation between systemic iron parameters (SIP) and substantia nigra (SN) iron deposits, as assessed by transcranial sonography (TCS) in restless legs syndrome (RLS). Methods We conducted a cross-sectional study in RLS patients, from whom blood samples with SIP were obtained, consisting of total iron-binding capacity (TIBC), serum ferritin, hemoglobin, transferrin saturation (TSAT), serum iron, and serum transferrin. TCS was performed over the SN, and the substantia nigra echogenicity index (SNEI) was determined according to established methods. Symptom severity was evaluated using the international restless legs scale (IRLS). A Spearman correlation was performed. Results A total of 167 patients were studied. Correlations between SNEI and SIP were as follows: serum ferritin (R = 0.0422; n.s.), TSAT (R = 0.0883; n.s.), TIBC (R = −0.1091; n.s.), serum transferrin (R = −0.0420; n.s.), hemoglobin (R = 0.0185; n.s.), serum iron (R = 0.0389; n.s.). No correlation was found with age and IRLS (R = 0.1375; n.s. and R = 0.0880, n.s., respectively). Conclusions SIP are not correlated with SN iron content in RLS, quantified by means of TCS. TCS of the SN might be a more valid estimate and could be useful in the evaluation of RLS patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread around the world since it emerged in Wuhan and coronavirus disease 2019 (COVID-19) has become a pandemic1. There is still little information regarding possible neurologic complications of this spread. Herein, we describe a patient with Guillain-Barré syndrome (GBS) preceded by COVID-19, raising the possibility of a causal relationship.

Objective To evaluate the incidence of iron overload and anaphylaxis following intravenous (IV) iron treatment of restless legs syndrome (RLS). Methods A total of 58 consecutive RLS patients, meeting clinical requirements for IV iron treatment according to current IRLSSG guidelines were recruited. IV iron treatment consisted of two 500 mg infusions of ferric carboxymaltose (FCM) administered five days apart. During each of the three follow-up visits we obtained blood samples, substantia nigra echogenity index (SNEI) by means of transcranial sonography (TCS), and assessed the severity of RLS symptoms (IRLS scale). “Iron overload risk” was defined as transferrin saturation (TSAT) > 45% on two consecutive follow-up visits. In patients who had a reduction in systemic iron levels following treatment, an additional 500 mg of FCM was administered when feasible. In such cases an additional two follow-up visits were performed. Results Among the total sample, only 2/58 participants met criteria for iron overload risk. They had no evidence of liver damage and did not require additional treatment. Among the 21 patients receiving an additional 500 mg infusion after, only one patient was diagnosed with iron overload risk. Among these three patients, only one was a hemochromatosis gene carrier. No anaphylaxis or other side-effects were reported. Conclusions In real-life clinical conditions, the risk of iron overload is low when IV FCM is administered according to the safety limits defined in the current RLS treatment guidelines. However, a close clinical follow-up with periodic blood sampling for iron status, is needed.

The main purpose of this manuscript is to review the existing clinical evidence about when iron replacement therapy should be initiated for RLS/WED, and how it should be administered (oral vs. intravenous). Our knowledge of the pathophysiology of restless legs syndrome/Willis-Ekbom (RLS/WED) continues to grow, revealing the existence of brain iron deficiency as the most well-known biological alteration behind this disorder. Since iron replacement therapy in RLS/WED is one of the first-line available treatments, its indication should be considered periodically, at both the beginning and during the follow-up. There is more and more evidence sustaining that the proper use of iron replacement therapy may lead to a reduction in symptomatic drug requirements, and therefore minimize the risk of complications that may result from their long-term use. For all the above, treatment paradigms for RLS/WED, previously based on symptomatic drugs, are changing, giving iron replacement therapy the importance it merits. Thus, it is essential for neurologists to be updated on why, when, and how to use iron in RLS/WED.