• Accelerated intermittent theta burst transcranial magnetic stimulation of the dorsolateral prefrontal cortex for chronic knee osteoarthritis pain

  Tanasescu, Radu (2025)

  OBJECTIVE: This study assessed feasibility, safety, and tolerability of accelerated intermittent theta burst stimulation (aiTBS) with effective connectivity-guidance targeting the left dorsolateral prefrontal cortex (lDLPFC) from the right anterior insular (rAI) in chronic knee osteoarthritis pain., METHODS: The BoostCPM clinical trial (ISRCTN15404076) was a randomized, sham-controlled, single-blind, parallel-group pilot study in patients with mild-moderate chronic pain. Participants were assigned 2:1 (active: sham) aiTBS for 4 consecutive days (totaling 36,000 pulses) at a daily dose of 9000 pulses (5 sessions of 1800 pulses). Primary outcomes included safety, tolerability, pain-related and affective outcomes, and quantitative sensory testing., RESULTS: 45 participants received active (n = 33) or sham (n = 12) aiTBS. No serious adverse events were recorded, and protocol adherence (tolerability) was 80.6 % and 100 % for active and sham. Follow-up response rate was 78.1 % and overall acceptance/satisfaction was 89 %. Pain relief was observed immediately after treatment and lasted 16 weeks with clinically meaningful reduction of pain burden, but no differences between groups., CONCLUSIONS: aiTBS with rAI-connected lDLPFC targeting is a safe, well tolerated, feasible, and acceptable intervention in chronic pain patients. However, we found no additional improvements compared to sham., SIGNIFICANCE: Further studies of aiTBS and lDLPFC targeting for pain relief are warranted. Copyright © 2025 The Author(s). Published by Elsevier B.V. All rights reserved.
• Acute inflammatory diseases of the central nervous system after SARS-CoV-2 vaccination

  Tanasescu, Radu (2023)

  Background and objectives: Acute inflammatory CNS diseases include neuromyelitis optica spectrum disorders (NMOSDs) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Both MOGAD and acute disseminated encephalomyelitis (ADEM) have been reported after vaccination. Consequently, the mass SARS-CoV-2 vaccination program could result in increased rates of these conditions. We described the features of patients presenting with new acute CNS demyelination resembling NMOSDs or MOGAD within 8 weeks of SARS-CoV-2 vaccination. Methods: The study included a prospective case series of patients referred to highly specialized NMOSD services in the UK from the introduction of SARS-CoV-2 vaccination program up to May 2022. Twenty-five patients presented with new optic neuritis (ON) and/or transverse myelitis (TM) ± other CNS inflammation within 8 weeks of vaccination with either AstraZeneca (ChAdOx1S) or Pfizer (BNT162b2) vaccines. Their clinical records and paraclinical investigations including MRI scans were reviewed. Serologic testing for antibodies to myelin oligodendrocyte glycoprotein (MOG) and aquaporin 4 (AQP4) was performed using live cell-based assays. Patients' outcomes were graded good, moderate, or poor based on the last clinical assessment. Results: Of 25 patients identified (median age 38 years, 14 female), 12 (48%) had MOG antibodies (MOGIgG+), 2 (8%) had aquaporin 4 antibodies (AQP4IgG+), and 11 (44%) had neither. Twelve of 14 (86%) antibody-positive patients received the ChAdOx1S vaccine. MOGIgG+ patients presented most commonly with TM (10/12, 83%), frequently in combination with ADEM-like brain/brainstem lesions (6/12, 50%). Transverse myelitis was longitudinally extensive in 7 of the 10 patients. A peak in new MOGAD cases in Spring 2021 was attributable to postvaccine cases. Both AQP4IgG+ patients presented with brain lesions and TM. Four of 6 (67%) seronegative ChAdOx1S recipients experienced longitudinally extensive TM (LETM) compared with 1 of 5 (20%) of the BNT162b2 group, and facial nerve inflammation was reported only in ChAdOx1S recipients (2/5, 40%). Guillain-Barre syndrome was confirmed in 1 seronegative ChAdOx1S recipient and suspected in another. Discussion: ChAdOx1S was associated with 12/14 antibody-positive cases, the majority MOGAD. MOGAD patients presented atypically, only 2 with isolated ON (1 after BNT162b2 vaccine) but with frequent ADEM-like brain lesions and LETM. Within the seronegative group, phenotypic differences were observed between ChAdOx1S and BNT162b2 recipients. These observations might support a causative role of the ChAdOx1S vaccine in inflammatory CNS disease and particularly MOGAD. Further study of this cohort could provide insights into vaccine-associated immunopathology.
• An update on the use of sphingosine 1-phosphate receptor modulators for the treatment of relapsing multiple sclerosis

  Papathanasiou, Athanasios; Evangelou, Nikos; Constantinescu, Cris S.; Tanasescu, Radu (2023)

  Introduction: Multiple sclerosis (MS) is an immune-mediated disorder of the CNS manifested by recurrent attacks of neurological symptoms (related to focal inflammation) and gradual disability accrual (related to progressive neurodegeneration and neuroinflammation). Sphingosine-1-phosphate-receptor (S1PR) modulators are a class of oral disease-modifying therapies (DMTs) for relapsing MS. The first S1PR modulator developed and approved for MS was fingolimod, followed by siponimod, ozanimod, and ponesimod. All are S1P analogues with different S1PR-subtype selectivity. They restrain the S1P-dependent lymphocyte egress from lymph nodes by binding the lymphocytic S1P-subtype-1-receptor. Depending on their pharmacodynamics and pharmacokinetics, they can also interfere with other biological functions. Areas covered: Our narrative review covers the PubMed English literature on S1PR modulators in MS until August 2022. We discuss their pharmacology, efficacy, safety profile, and risk management recommendations based on the results of phase II and III clinical trials. We briefly address their impact on the risk of infections and vaccines efficacy. Expert opinion: S1PR modulators decrease relapse rate and may modestly delay disease progression in people with relapsing MS. Aside their established benefit, their place and timing within the long-term DMT strategy in MS, as well as their immunological effects in the new and evolving context of the post-COVID-19 pandemic and vaccination campaigns warrant further study.Copyright © 2023 Informa UK Limited, trading as Taylor & Francis Group.
• Brain connectivity-guided, optimised theta burst transcranial magnetic stimulation to improve central pain modulation in knee osteoarthritis pain (BoostCPM): Protocol of a pilot randomised clinical trial in a secondary care setting in the UK

  Tanasescu, Radu (2023)

  Introduction Chronic pain is a common health problem that is not efficiently managed by standard analgesic treatments. There is evidence that treatment resistance may result from maladaptive brain changes in areas that are fundamental to the perception of pain. Knee osteoarthritis is one of the most prevalent causes of chronic pain and commonly associated with negative affect. Chronic knee osteoarthritis pain is also associated with altered right anterior insula functional connectivity. We posit that reversal of these brain circuit alterations may be critical to alleviate chronic pain and associated negative affect, and that this can be achieved through non-invasive neuromodulation techniques. Despite growing interest in non-invasive neuromodulation for pain relief and proven efficacy in depression, results in chronic pain are mixed with limited high-quality evidence for clinical and mechanistic efficacy. Limitations include patient heterogeneity, imprecision of target selection, uncertain blinding and protocols that may deliver pulses at subclinical efficacy. Methods and analysis We hence developed an optimised treatment protocol of connectivity-guided intermittent theta-burst stimulation (iTBS) targeting the left dorsolateral prefrontal cortex with accelerated delivery on four consecutive days (allowing 4 days within the same week as protocol variation) with five daily treatment sessions that will be piloted in a sham-controlled design in 45 participants with chronic knee pain. This pilot study protocol will assess feasibility, tolerability and explore mechanistic efficacy through serial functional/structural magnetic resonance imaging (MRI) and quantitative sensory testing. Ethics and dissemination This pilot trial has been approved by the Ethics Committee Cornwall and Plymouth. Results of the pilot trial will be submitted to peer-reviewed journals, presented at research conferences and may be shared with participants and PPI/E advisors. Trial registration number ISRCTN15404076.Copyright © 2023 BMJ Publishing Group. All rights reserved.
• Cerebral cortical encephalitis in adults with myelin oligodendrocyte glycoprotein antibody-associated disease: A national case series

  Tanasescu, Radu; Papathanasiou, Athanasios; Constantinescu, Cris S. (2025)

  Background and purpose: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a relatively recently described disease, most commonly presenting with optic neuritis and longitudinally extensive transverse myelitis. Cerebral cortical encephalitis is a rare manifestation of MOGAD. Method(s): We identified patients presenting with cerebral cortical encephalitis with positive MOG antibodies in serum across a large specialized service. Demographic and clinical information were collected. We describe clinical and laboratory characteristics, treatment response, and subsequent relapse risk in adults presenting with this phenotype. Result(s): We identified eight patients meeting clinical criteria for cerebral cortical encephalitis with MOG antibodies. All had seizures; four had focal onset seizures with or without secondary generalization. Two patients exhibited encephalopathy, and six demonstrated focal neurological deficits at presentation. All had fluid-attenuated inversion recovery hyperintensities. Five of eight displayed cerebral swelling, and two of eight displayed leptomeningeal enhancement. Where cerebrospinal fluid (CSF) results were available, five of seven had CSF pleocytosis, protein was raised in two of seven, and one patient had oligoclonal bands unique to CSF. Median time to seizure control was 1.25 months, and all clinical features and magnetic resonance imaging abnormalities resolved. Four of eight patients (50%) had a clinical relapse, with a median time to relapse of 6.4 months. Conclusion(s): Cerebral cortical encephalitis appears to share similar CSF findings, steroid responsiveness, and risk of relapse with other clinical manifestations of MOGAD. This informs treatment decisions and patient counselling.Copyright © 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.

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