Adding a Second iTBS Block in 15 or 60 Min Time Interval Does Not Increase iTBS Effects on Motor Cortex Excitability and the Responder Rates.

The use of metaplasticity-based intermittent theta-burst stimulation (iTBS) protocols including several stimulation blocks could be a possible approach to increasing stimulation effectiveness. Our aim was to investigate the neurophysiological effects of two protocols with a short and a long interval between blocks. Seventeen healthy volunteers received four protocols in a pseudorandomized order: iTBS 0-15 (two blocks of active iTBS of primary motor cortex (M1) separated by 15 min and a control stimulation block of the vertex in 60 min from the first block); iTBS 0-60 (active iTBS, a control block in 15 min, and an active block in 60 min); iTBS 0 (active iTBS and two control blocks with the same intervals); and Control (three control blocks). The motor evoked potentials (MEPs) were measured before the first and after the second and third blocks. We have shown no significant differences between the effects of the protocols on both the motor cortex excitability and the responder rates. No significant changes of MEPs were observed after all the protocols. The reliability for the responsiveness to a single block between two sessions was insignificant. Our data confirm low reproducibility of the response to iTBS and suggest that the use of repeated protocols does not increase the responder rates or neurophysiological effects of iTBS.

Levamisole-Induced Leukoencephalopathy in Russia: Analysis of 30 Cases.

AIMS: The study aims to raise medical specialists' awareness regarding the severity of possible complications of levamisole administration, and demonstrate the role of accurate medical history collection in a differential diagnosis. BACKGROUND: Levamisole, an anthelmintic drug with immunomodulatory effects, has long been used worldwide till the early 2000s, when its association with demyelinating leukoencephalopathy was established. However, in the developing countries, it is still widely used for the prevention and treatment of helminthic invasion in humans. The actual prevalence of levamisole-induced multiple inflammatory leukoencephalopathy (LEV-induced MIL) in Russia remains unknown, and therefore, the study of its frequency and characteristics is indisputably important. OBJECTIVES: The objective of this study is to determine the clinical features and MRI findings of levamisole- induced MIL in the Russian population, and to analyse the frequency of diagnostic errors at the initial assessment. METHODS: A single-center retrospective analysis of total 30 patients who were diagnosed with LEV- induced MIL and attended the Research Center of Neurology was conducted. Inclusion criteria were 1) clinically: acute or subacute polysymptomatic onset of neurological disturbances, 2) MRI: multifocal demyelinating lesion with no evidence of dissemination in time, 3) anamnestic data: levamisole exposure from 2 to 8 weeks before symptoms onset as well as monophasic disease course (absence of relapses according to follow up assessments up to 3 years). RESULTS: Clinically, presentation with constitutional symptoms including headache, fever, fatigue and myalgia, focal motor disturbances and dysarthria prevailed in our cohort. On the brain MRI, multiple foci of demyelination with simultaneous gadolinium enhancement were observed. The link between neurological symptoms and levamisole intake has often been detected only during follow- up assessments. Patients were most often misdiagnosed with acute disseminated encephalomyelitis, stroke and multiple sclerosis. In most cases, LEV-induced MIL was successfully treated with intravenous corticosteroids and/or plasma exchange (PLEX), however, residual neurologic symptoms were preserved in some patients. Additionally, two detailed clinical cases of patients being initially misdiagnosed are presented in the article. CONCLUSION: The differential diagnosis remains difficult for suspected cases of LEV-induced MIL that could lead to delayed therapy initiation, and consequently incomplete recovery. Growing evidence suggests that a single administration of levamisole even in low doses might potentially lead to severe neurological deficit or death. Therefore, changes in medication management policies are required in order to prevent the uncontrolled use of levamisole.

Combining HF rTMS over the Left DLPFC with Concurrent Cognitive Activity for the Offline Modulation of Working Memory in Healthy Volunteers: A Proof-of-Concept Study.

It has been proposed that the effectiveness of non-invasive brain stimulation (NIBS) as a cognitive enhancement technique may be enhanced by combining the stimulation with concurrent cognitive activity. However, the benefits of such a combination in comparison to protocols without ongoing cognitive activity have not yet been studied. In the present study, we investigate the effects of fMRI-guided high-frequency repetitive transcranial magnetic stimulation (HF rTMS) over the left dorsolateral prefrontal cortex (DLPFC) on working memory (WM) in healthy volunteers, using an n-back task with spatial and verbal stimuli and a spatial span task. In two combined protocols (TMS + WM + (maintenance) and TMS + WM + (rest)) trains of stimuli were applied in the maintenance and rest periods of the modified Sternberg task, respectively. We compared them to HF rTMS without a cognitive load (TMS + WM-) and control stimulation (TMS - WM + (maintenance)). No serious adverse effects appeared in this study. Among all protocols, significant effects on WM were shown only for the TMS + WM- with oppositely directed influences of this protocol on storage and manipulation in spatial WM. Moreover, there was a significant difference between the effects of TMS + WM- and TMS + WM + (maintenance), suggesting that simultaneous cognitive activity does not necessarily lead to an increase in TMS effects.