Mechanisms of Nerve Damage in Neuropathies Associated with Hematological Diseases: Lesson from Nerve Biopsies

Briani, Chiara; Ferrari, Sergio; Campagnolo, Marta; Tagliapietra, Matteo; Castellani, Francesca; Salvalaggio, Alessandro; Mariotto, Sara; Visentin, Andrea; Cavallaro, Tiziana

doi:10.3390/brainsci11020132

Cited by 12 publications

(6 citation statements)

References 97 publications

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“…Anti-MAG antibodies are central in the pathogenesis causing complement mediated demyelination and nerve damage [ 11 ]. Proteins in blood reflecting nerve damage are increasingly used as biomarkers of disease activity in other PN.…”

Section: Introductionmentioning

confidence: 99%

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Serum neurofilament light chain, contactin-1 and complement activation in anti-MAG IgM paraprotein-related peripheral neuropathy

et al. 2022

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Introduction In anti-myelin-associated glycoprotein IgM paraprotein-related peripheral neuropathy (anti-MAG PN), there is a lack of reliable biomarkers to select patients eligible for therapy and for evaluating treatment effects, both in routine practice and in clinical trials. Neurofilament light chain (NfL) and contactin-1 (CNTN1) can serve as markers of axonal and paranodal damage. Complement activation is involved in the pathogenesis in anti-MAG PN. We, therefore, hypothesized that serum NfL, CNTN1, C3b/c and C4b/c may function as biomarkers of disease activity in anti-MAG PN. Methods In this prospective cohort study, we included 24 treatment-naïve patients with anti-MAG PN (mean age 69 years, 57% male) that had IgM paraproteinemia, a high IgM MAG-antibody, and clinical diagnosis of anti-MAG PN by a neurologist specialized in peripheral nerve disorders. We measured serum NfL, CNTN1, C3b/c and C4b/c, reference values were based on healthy controls. As controls, 10 treatment-naïve patients with IgM Monoclonal gammopathy of undetermined significance (MGUS) or Waldenström’s Macroglobulinemia (mean age 69 years, 60% male) without signs of neuropathy were included (non-PN). Results NfL, CNTN1 levels in serum were mostly normal in anti-MAG PN patients and comparable to non-PN patients. C3b/c and C4b/c levels were normal in anti-MAG PN patients. Conclusion Our results do not support serum NfL, CNTN1, and C3b/c and C4b/c as potential biomarkers in anti-MAG PN, although we cannot exclude that subgroups or subtle abnormalities could be found in a much larger cohort with longitudinal follow-up.

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Section: Introductionmentioning

confidence: 99%

“…The complement system is known to be involved in anti-MAG PN based on nerve biopsy studies. When IgM antibodies bind MAG, complement mediated demyelination occurs and deposits of IgM and complement can be observed in myelin sheets [ 11 ]. Serum CNTN1 and complement activation markers have not been studied yet in anti-MAG PN.…”

Section: Introductionmentioning

confidence: 99%

Serum neurofilament light chain, contactin-1 and complement activation in anti-MAG IgM paraprotein-related peripheral neuropathy

et al. 2022

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“…While pSS patients with established vitamin B12 deficit are subject to developing PNS symptoms due to metabolic dysfunction in large nerve fibers, the borderline group displaying in range levels of B12, but adjacent to the lower limit might also be prone to develop peripheral nervous system complications. Whether the pathophysiological etiology is determined by decreased B12 levels or by accentuated peripheral nerve damage through DRG affection or vasa nervorum vasculitis it remains unclear [29,30].…”

Section: Author Contributionsmentioning

confidence: 99%

Decreased Protein Levels and Vitamin B12 Plasma Concentration in Primary Sjögren Syndrome are Associated with Peripheral Neuropathy: A Case-Control Study

Ancuta¹,

Maria²,

Mihnea³

et al. 2022

J Musculoskelet Disord Treat

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Background: Prognostic factors for peripheral nervous system (PNS) manifestations in primary Sjögren Syndrome (pSS) are essential for predicting and preventing diseaserelated disability. Given the established relationship between vitamin B12 deficiency and pSS, we aimed to investigate the predictive value of low B12 concentration for Sjögren's induced peripheral neuropathy (PN). Methods:We conducted a case-control study which included 96 patients with pSS, 13 of which were diagnosed with PN. We measured multiple nutrition-related biomarkers, including total protein levels, vitamin B12, folic acid, and iron concentrations.Results: Total protein serum concentration was lower in PN diagnosed patients compared to the control group (7.15 vs. 7.64 g/dL, p < 0.05). In addition, the mean concentration of plasma B12 was decreased in the PN group with regard to control (431.92 vs. 588.43 ng/L, p < 0.05). However, a significant predictive pattern was not established for either of the biomarkers. Conclusions:Peripheral neuropathy in pSS is associated with reduced serum protein and vitamin B12 levels. Although a predictive correlation was not demonstrated, the screening for early deficit is justified and recommended.

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“…In most cases it is a condition with “undetermined significance” (monoclonal gammopathy of undetermined significance [MGUS]), but in some cases monoclonal gammopathy may be related to a hematological disorder. Paraproteinemic demyelinating immunoglobulin M (IgM)‐related neuropathy (PDN) is often characterized by a chronic, slowly progressive, predominantly sensory distal symmetric neuropathy with ataxia, often with postural tremor at the upper limbs, with relatively mild or no weakness at the beginning of disease [ 2 , 3 , 4 , 5 ]. A hallmark of PDN is evidence of anti‐myelin‐associated glycoprotein IgM antibodies (anti‐MAG) in the serum [ 6 ], with these being present in approximately half of all patients [ 7 , 8 , 9 , 10 , 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Efficacy of rituximab in anti‐myelin‐associated glycoprotein demyelinating polyneuropathy: Clinical, hematological and neurophysiological correlations during 2 years of follow‐up

Parisi

Dogliotti

Clerico

et al. 2022

Euro J of Neurology

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Background and purpose We evaluated the clinical and neurophysiological efficacy of rituximab (RTX) in a neurophysiologically homogeneous group of patients with monoclonal gammopathy and immunoglobulin M (IgM) anti‐myelin‐associated glycoprotein antibody (anti‐MAG) demyelinating polyneuropathy. Methods Twenty three anti‐MAG‐positive polyneuropathic patients were prospectively evaluated before and for 2 years after treatment with RTX 375 mg/m2. The Inflammatory Neuropathy Cause and Treatment (INCAT) disability scale (INCAT‐ds), modified INCAT sensory score (mISS), Medical Research Council sum score, Patients’ Global Impression of Change scale were used, IgM levels were assessed and extensive electrophysiological examinations were performed before (T0) and 1 year (T1) and 2 years (T2) after RTX treatment. Results At T1 and T2 there was a significant reduction from T0 both in mISS and in INCAT‐ds, with a p value < 0.001 in the inferential Friedman's test overall analysis. Ulnar nerve Terminal Latency Index and distal motor latency significantly changed from T0 to T1 and in the overall analysis (p = 0.001 and p = 0.002), and ulnar nerve sensory nerve action potential (SNAP) amplitude was significantly increased at T2 from T1, with a p value < 0.001 in the overall analysis. Analysis of the receiver‐operating characteristic curves showed that a 41.8% increase in SNAP amplitude in the ulnar nerve at T2 from T0 was a fair predictor of a mISS reduction of ≥2 points (area under the curve 0.85; p = 0.005; sensitivity: 90.9%, specificity: 83.3%). Conclusions This study suggests that RTX is effective in patients with clinically active demyelinating anti‐MAG neuropathy over 2 years of follow‐up, and that some neurophysiological variables might be useful for monitoring this efficacy.

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Mechanisms of Nerve Damage in Neuropathies Associated with Hematological Diseases: Lesson from Nerve Biopsies

Cited by 12 publications

References 97 publications

Serum neurofilament light chain, contactin-1 and complement activation in anti-MAG IgM paraprotein-related peripheral neuropathy

Serum neurofilament light chain, contactin-1 and complement activation in anti-MAG IgM paraprotein-related peripheral neuropathy

Decreased Protein Levels and Vitamin B12 Plasma Concentration in Primary Sjögren Syndrome are Associated with Peripheral Neuropathy: A Case-Control Study

Efficacy of rituximab in anti‐myelin‐associated glycoprotein demyelinating polyneuropathy: Clinical, hematological and neurophysiological correlations during 2 years of follow‐up

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