The pathogenesis of multiple sclerosis (MS) suggests that, in genetically susceptible subjects, T lymphocytes undergo activation in the peripheral compartment, pass through the BBB, and cause damage in the CNS. They produce pro-inflammatory cytokines; induce cytotoxic activities in microglia and astrocytes with the accumulation of reactive oxygen species, reactive nitrogen species, and other highly reactive radicals; activate B cells and macrophages and stimulate the complement system. Inflammation and neurodegeneration are involved from the very beginning of the disease. They can both be affected by oxidative stress (OS) with different emphases depending on the time course of MS. Thus, OS initiates and supports inflammatory processes in the active phase, while in the chronic phase it supports neurodegenerative processes. A still unresolved issue in overcoming OS-induced lesions in MS is the insufficient endogenous activation of the Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) pathway, which under normal conditions plays an essential role in mitochondria protection, OS, neuroinflammation, and degeneration. Thus, the search for approaches aiming to elevate endogenous Nrf2 activation is capable of protecting the brain against oxidative damage. However, exogenous Nrf2 activators themselves are not without drawbacks, necessitating the search for new non-pharmacological therapeutic approaches to modulate OS. The purpose of the present review is to provide some relevant preclinical and clinical examples, focusing on certain exogenous and endogenous Nrf2 activators and the modulation of therapeutic plasma exchange (TPE). The increased plasma levels of nerve growth factor (NGF) in response to TPE treatment of MS patients suggest their antioxidant potential for endogenous Nrf2 enhancement via NGF/TrkA/PI3K/Akt and NGF/p75NTR/ceramide-PKCζ/CK2 signaling pathways.

Therapeutic plasma exchange (TPE) is an efficient extracorporeal blood purification technique to remove circulating autoantibodies and other pathogenic substances. Its mechanism of action in immune-mediated neurological disorders includes immediate intravascular reduction of autoantibody concentration, pulsed induction of antibody redistribution, and subsequent immunomodulatory changes. Conventional TPE with 1 to 1.5 total plasma volume (TPV) exchange is a well-established treatment in Guillain-Barre Syndrome, Chronic Inflammatory Demyelinating Polyradiculoneuropathy, Neuromyelitis Optica Spectrum Disorder, Myasthenia Gravis and Multiple Sclerosis. There is insufficient evidence for the efficacy of so-called low volume plasma exchange (LVPE) (<1 TPV exchange) implemented either by the conventional or by a novel nanomembrane-based TPE in these neurological conditions, including their impact on conductivity and neuroregenerative recovery. In this narrative review, we focus on the role of nanomembrane-based technology as an alternative LVPE treatment option in these neurological conditions. Nanomembrane-based technology is a promising type of TPE, which seems to share the basic advantages of the conventional one, but probably with fewer adverse effects. It could play a valuable role in patient management by ameliorating neurological symptoms, improving disability, and reducing oxidative stress in a cost-effective way. Further research is needed to identify which patients benefit most from this novel TPE technology.

According to the American Academy of Neurology 2011 guidelines, there is insufficient evidence to support or refute the use of therapeutic plasma exchange (TPE) for myasthenia gravis (MG). The goal of this study was to determine whether a novel nanomembrane-based TPE could be useful in the treatment of MG. Thirty-six adult patients, MGFA 4/4B and 5, with acute MG episodes were enrolled into a single-center retrospective before-and-after study to compare a conventional treatment group (n = 24) with a nanomembrane-based TPE group (n = 12). TPE or intravenous immunoglobulins (IVIG) infusions were used in impending/manifested myasthenic crises, especially in patients at high-risk for prolonged invasive ventilation (IMV) and in those tolerating non-invasive ventilation (NIV). The clinical improvement was assessed using the Myasthenia Muscle Score (0–100), with ≥20 increase for responders. The primary outcome measures included the rates of implemented TPE, IVIG, and corticosteroids immunotherapies, NIV/IMV, early tracheotomy, MMS scores, extubation time, neuro-ICU/hospital LOS, complications, and mortality rates. The univariate analysis found that IMV was lower in the nanomembrane-based group (42%) compared to the conventional treatment group (83%) (p = 0.02). The multivariate analysis using binary logistic regression revealed TPE and NIV as independent predictors for short-term (≤7 days) respiratory support (p = 0.014 for TPE; p = 0.002 for NIV). The novel TPE technology moved our clinical practice towards proactive rather than protective treatment in reducing prolonged IMV during MG acute exacerbations.

Objective. Dexamethasone could be an effective prophylactic agent for the prevention of pain flares after palliative radiotherapy (RT) for uncomplicated bone metastases. To date, there are no data on its prophylactic coanalgesic (opioid-sparing) effect after RT in patients with complicated bone metastases compared to uncomplicated ones, which is the aim of our study. Methods. Twenty-nine American Society of Anaesthesiologists (ASA) III-IV patients, aged ≥18, treated with single-fraction 8 Gy/1 or multi-fraction 20 Gy/5 RT for painful uncomplicated bone metastases (steroid naïve patients, n = 14) or complicated ones (steroid non-naïve patients, n = 15), were examined retrospectively. All patients received parenteral dexamethasone (4 mg or 8 mg daily, 1 hour before RT, followed by the same dose for the next 4 days) along with their background and breakthrough pain opioid intake (morphine equivalents) during their 5-day in-hospital stay. Pain severity (numeric rating scale) and analgesic consumption were recorded at admission, daily during the hospital stay, and for 10 days following treatment. Binary logistic regression was used to determine predictive factors for pain flare occurrence. Results. A higher ASA score is the only determinant positively influencing opioid consumption ( = 0.018) and pain flare as well (OR = 15.00; 95% CI: 2, 24–100, 48; = 0.005). Lower dose 4 mg dexamethasone was revealed as a moderate analgesic agent in steroid naïve patients with no side effects, whereas in steroid non-naïve patients the predominantly higher dose 8 mg dexamethasone had minimal impact on pain flares prevention at the expense of more pronounced immunosuppression ( = 0.039). Conclusions. Irrespective of the supporting evidence of dexamethasone potential for prevention of RT-induced pain flare, our data failed to reveal its efficacy in the real practice world (a case mix of uncomplicated and complicated bone metastases). Further dose-effect bigger studies are needed, identifying optimal doses of dexamethasone intake and its optimal duration in high-risk patients.

Multiple sclerosis (MS) is predominantly an immune-mediated disease of the central nervous system (CNS) of unknown etiology with a possible genetic predisposition and effect of certain environmental factors. It is generally accepted that the disease begins with an autoimmune inflammatory reaction targeting oligodendrocytes followed by a rapid depletion of their regenerative capacity with subsequent permanent neurodegenerative changes and disability. Recent research highlights the central role of B lymphocytes and the corresponding IgG and IgM autoantibodies in newly forming MS lesions. Thus, their removal along with the modulation of certain bioactive molecules to improve neuroprotection using therapeutic plasma exchange (TPE) becomes of utmost importance. Recently, it has been proposed to determine the levels and precise effects of both beneficial and harmful components in the serum of MS patients undergoing TPE to serve as markers for appropriate TPE protocols. In this review we discuss some relevant examples, focusing on the removal of pathogenic circulating factors and altering the plasma levels of nerve growth factor and sphingosine-1-phosphate by TPE. Altered plasma levels of the reviewed molecular compounds in response to TPE reflect a successful reduction of the pro-inflammatory burden at the expense of an increase in anti-inflammatory potential in the circulatory and CNS compartments.