90 research outputs found
Assessing the benefit of treatment in chronic inflammatory demyelinating polyneuropathy: the challenges of clinical practice
Current Proposed Mechanisms of Action of Intravenous Immunoglobulins in Inflammatory Neuropathies
Intravenous immunoglobulins (IVIg) have been shown in a number of trials, to be an effective treatment for the three main types of inflammatory neuropathies: Guillain-Barré Syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), and multifocal motor neuropathy (MMN). IVIg is thought to exert its immunomodulatory effects by affecting several components of the immune system including B-cells, T-cells, macrophages, complement, cytokines and cellular adhesion molecules. This article reviews the published evidence and the principal postulated mechanisms of action of intravenous immunoglobulins with special emphasis on inflammatory neuropathies
Chronic Inflammatory Demyelinating Polyradiculoneuropathy: Current Therapeutic Approaches and Future Outlooks
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a treatable autoimmune disorder, for which different treatment options are available. Current first-line evidence-based therapies for CIDP include intravenous and subcutaneous immunoglobulins, corticosteroids and plasma exchanges. Despite lack of evidence, cyclophosphamide, rituximab and mycophenolate mofetil are commonly used in circumstances of refractoriness and, more debatably, of perceived overdependence on first-line therapies. Rituximab is currently the object of a randomized controlled trial for CIDP. Based on case series, and although rarely considered, haematopoietic autologous stem cell transplants may be effective in refractory disease, with low mortality and high remission rates. A new therapeutic option has appeared with efgartigimod, a neonatal Fc receptor blocker, recently shown to significantly lower relapse rate versus placebo, after withdrawal from previous immunotherapy. Other neonatal Fc receptor blockers, nipocalimab and batoclimab, are under study. The C1 complement-inhibitor SAR445088, acting in the proximal portion of the classical complement system, is currently the subject of a new study in treatment-responsive, refractory and treatment-naïve subjects. Finally, Bruton Tyrosine Kinase inhibitors, which exert anti-B cell effects, may represent another future research avenue. The widening of the therapeutic armamentarium enhances the need for improved evaluation of treatment effects and reliable biomarkers in CIDP
Comparative value and determinants of suitability of outcome measures in treated chronic inflammatory demyelinating polyneuropathy
Introduction: The comparative value and suitability of outcome measures are uncertain in chronic inflammatory demyelinating polyneuropathy (CIDP). Methods: We studied 35 patients with CIDP using the Overall Neuropathy Limitation Scale (ONLS), the inflammatory Rasch-built Overall Disability Scale (I-RODS), and the Medical Research Council Sum Score (MRCSS). Results: Significant associations were determined between initial deficit and ONLS score (P =.002) and MRCSS improvement (P =.001) but not I-RODS score. A strong inverse correlation was observed between disease duration and I-RODS score(P =.002) but not ONLS/MRCSS improvement. A strong association was observed between age ≤ 40 years and I-RODS score (P =.001) but not ONLS/MRCSS improvement. When minimum important differences were used, ONLS and I-RODS sensitivities were comparable (P =.19). Discussion: Overall Neuropathy Limitation Scale and I-RODS are equally sensitive in identifying change. Ease of administration, better ability to detect improvement in severe disease, and greater amplitude responses throughout the disease and in older patients favor the ONLS. The I-RODS appears more useful in early disease/younger patients
Neuropsychiatric manifestations in inflammatory neuropathies:a systematic review
We conducted a systematic literature review on psychological and behavioral comorbidities in patients with inflammatory neuropathies. In Guillain-Barré syndrome (GBS), psychotic symptoms are reported during early stages in 30% of patients. Typical associations include mechanical ventilation, autonomic dysfunction, inability to communicate, and severe weakness. Anxiety and depression are frequent comorbidities. Anxiety may increase post-hospital admissions and be a predictor of mechanical ventilation. Post-traumatic stress disorder may affect up to 20% of ventilated patients. Sleep disturbances are common in early-stage GBS, affecting up to 50% of patients. In chronic inflammatory demyelinating polyradiculoneuropathy, memory and quality of sleep may be impaired. An independent link between depression and pre-treatment upper limb disability and ascites was reported in POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, M-protein, Skin) syndrome, with an association with early death. Hematological treatment of POEMS appears effective on depression. Published literature on psychological/behavioral manifestations in inflammatory neuropathies remains scarce, and further research is needed. This article is protected by copyright. All rights reserved
Corticosteroids for chronic inflammatory demyelinating polyradiculoneuropathy
Background: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a progressive or relapsing and remitting paralysing illness, probably due to an autoimmune response, which should benefit from corticosteroid treatment. Non-randomised studies suggest that corticosteroids are beneficial. Two commonly used corticosteroids are prednisone and prednisolone. Both are usually given as oral tablets. Prednisone is converted into prednisolone in the liver so that the effect of the two drugs is usually the same. Another corticosteroid, dexamethasone, is more potent and is used in smaller doses. The review was first published in 2001 and last updated in 2015; we undertook this update to identify any new evidence. Objectives: To assess the effects of corticosteroid treatment for CIDP compared to placebo or no treatment, and to compare the effects of different corticosteroid regimens. Search methods: On 8 November 2016, we searched the Cochrane Neuromuscular Specialised Register, Cochrane Central Register of Controlled Trials, MEDLINE, and Embase for randomised trials of corticosteroids for CIDP. We searched clinical trials registries for ongoing trials. Selection criteria: We included randomised controlled trials (RCTs) or quasi-RCTs of treatment with any corticosteroid or adrenocorticotrophic hormone for CIDP, diagnosed by an internationally accepted definition. Data collection and analysis: Two authors extracted data from included studies and assessed the risk of bias independently. The intended primary outcome was change in disability, with change in impairment after 12 weeks and side effects as secondary outcomes. We assessed strength of evidence using the GRADE approach. Main results: One non-blinded RCT comparing prednisone with no treatment in 35 eligible participants did not measure the primary outcome for this systematic review. The trial had a high risk of bias. Neuropathy Impairment Scale scores after 12 weeks improved in 12 of 19 participants randomised to prednisone, compared with five of 16 participants randomised to no treatment (risk ratio (RR) for improvement 2.02 (95% confidence interval (CI) 0.90 to 4.52; very low-quality evidence). The trial did not report side effects in detail, but one prednisone-treated participant died. A double-blind RCT comparing daily standard-dose oral prednisolone with monthly high-dose oral dexamethasone in 40 participants reported none of the prespecified outcomes for this review. The trial had a low risk of bias, but the quality of evidence was limited as it came from a single small study. There was little or no difference in number of participants who achieved remission (RR 1.11; 95% CI 0.50 to 2.45 in favour of monthly dexamethasone; moderate-quality evidence), or change in disability or impairment after one year (low-quality evidence). Change of grip strength or Medical Research Council (MRC) scores demonstrated little or no difference between groups (moderate-quality to low-quality evidence). Eight of 16 people in the prednisolone group and seven of 24 people in the dexamethasone group deteriorated. Side effects were similar with each regimen, except that sleeplessness was less common with monthly dexamethasone (low-quality evidence) as was moon facies (moon-shaped appearance of the face) (moderate-quality evidence). Experience from large non-randomised studies suggests that corticosteroids are beneficial, but long-term use causes serious side effects. Authors' conclusions: We are very uncertain about the effects of oral prednisone compared with no treatment, because the quality of evidence from the only RCT that exists is very low. Nevertheless, corticosteroids are commonly used in practice, supported by very low-quality evidence from observational studies. We also know from observational studies that corticosteroids carry the long-term risk of serious side effects. The efficacy of high-dose monthly oral dexamethasone is probably little different from that of daily standard-dose oral prednisolone. Most side effects occurred with similar frequencies in both groups, but with high-dose monthly oral dexamethasone moon facies is probably less common and sleeplessness may be less common than with oral prednisolone. We need further research to identify factors that predict response
Small fiber neuropathy in unexpected clinical settings: a review
Small fiber neuropathy (SFN) is being recognized with increasing frequency in neuromuscular practice due to improved diagnostic techniques. Although there are some common etiologies, up to one‐third of cases are considered idiopathic. In recent years, several disorders have unexpectedly been reported in association with SFN, on clinical grounds and complementary investigations, including quantitative sensory testing, intraepidermal nerve fiber density and confocal corneal microscopy. Knowledge of these disorders is important in clinical practice as increased awareness enables prompt diagnosis of SFN in these settings and early optimal therapeutic management of affected patients. Furthermore, these new developments may lead to a better understanding of the pathophysiologic mechanisms underlying SFN in these different disorders as well as, in some cases, an expanded spectrum of affected organs and systems. This article reviews these reported associations, their possible pathophysiologic bases, and the potential resulting management implications
Outcome measures for chronic inflammatory demyelinating polyneuropathy in research:relevance and applicability to clinical practice
Outcome measures are recommended in the management of chronic inflammatory demyelinating polyneuropathy (CIDP). Various scales have been proposed in recent years, some now commonly utilized in daily clinical practice. The available evidence base relies itself on randomized controlled trial data obtained over the past 30 years, with several studies using different primary and secondary outcomes. We here review the different outcome measures used in CIDP research in relation to those currently recommended for clinical management. We consider the evidence base for CIDP treatment from the primary and secondary outcomes used in these studies and attempt to assess how this may relate to current clinical practice of routine evaluation of treatment effects and long-term monitoring
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