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Reliable and responsive tools for monitoring disease activity and treatment outcomes in patients with neuropathies are lacking. With the emergence of ultrasensitive blood bioassays, proteins released with nerve damage are potentially useful response biomarkers for many neurological disorders, including polyneuropathies. In this review, we provide an overview of the existing literature focusing on potential applications in polyneuropathy clinical care and trials. Whilst several promising candidates have been identified, no studies have investigated if any of these proteins can serve as response biomarkers of longitudinal disease activity, except for neurofilament light (NfL). For NfL, limited evidence exists supporting a role as a response biomarker in Guillain-Barré syndrome, vasculitic neuropathy, and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Most evidence exists for NfL as a response biomarker in hereditary transthyretin-related amyloidosis (hATTR). At the present time, the role of NfL is therefore limited to a supporting clinical tool or exploratory endpoint in trials. Future developments will need to focus on the discovery of additional biomarkers for anatomically specific and other forms of nerve damage using high-throughput technologies and highly sensitive analytical platforms in adequality powered studies of appropriate design. For NfL, a better understanding of cut-off values, the relation to clinical symptoms and long-term disability as well as dynamics in serum on and off treatment is needed to further expand and proceed towards implementation., (© 2021. The Author(s).)

Strict glycemic control (SGC) is reported to have a beneficial effect on critical illness polyneuropathy/myopathy (CINM) and the duration of mechanical ventilation. The methodology used to diagnose CINM differs substantially in studies on this topic. This may influence the reported treatment effect. We reviewed literature on the effect of SGC on CINM and duration of ventilation by conducting a OVID Medline systematic electronic search of literature describing effects of SGC on occurrence of CINM and the effect of SGC on the duration of mechanical ventilation. A beneficial effect of SGC on CINM, diagnosed by needle myography, was reported in three studies. One of these studies showed that the incidence of weakness or failure to wean did not decrease by SGC, as the number of electrophysiological studies (EMG) ordered for these problems remained the same. Another study reported no improvement of muscle strength due to SGC. SGC reduced the duration of mechanical ventilation in three studies while six other studies did not report this beneficial effect. SGC seems to have a beneficial effect on CINM, but the reported risk reduction is likely to be an overestimation of the treatment effect due to the diagnostic methods used. Duration of mechanical ventilation may not be a reliable surrogate marker for CINM and a beneficial effect of SGC on this parameter has not been proven. We propose to use the recently developed diagnostic criteria for ICU-acquired weakness and critical illness neuromyopathy in future studies.

Background: INCbase is an international, multicenter prospective observational study using a customizable web-based modular registry to study the clinical, biological and electrophysiological variation and boundaries of chronic inflammatory demyelinating polyneuropathy (CIDP). The primary objective of INCbase is to develop and validate a clinical prediction model for treatment response. Methods: All patients meeting clinical criteria for CIDP can be included in INCbase. Collected data include demographics, clinical history, diagnostics and various domains of clinical outcomes. Data is collected at a minimum of every 6 months for two years, and more frequently at the discretion of the investigational site to allow for assessment of unexpected changes in treatment response or clinical status. Participants can be enrolled in various sub-studies designed to capture data relevant to specific groups of interest. Data is entered directly into the web-based data entry system by local investigators and/or participants. Collection and local storage of biomaterial is optional. To develop a clinical prediction model for treatment response, newly diagnosed patients with active disease warranting start of first-line treatment will be included. The study population will be split into a development and validation cohort. Univariate and multivariate logistic regression analysis will be used to identify and combine predictors at start of treatment for treatment response at six months. Model performance will be assessed through discrimination and calibration in an external validation cohort. The externally validated prediction model will be made available to researchers and clinicians on the INCbase website. Discussion: With this study, we aim to create a clinically relevant and implementable prediction model for treatment response to first line treatments in CIDP. INCbase enrollment started in April 2021, with 29 centers across 8 countries and 303 patients participating to date. This collaborative effort between academia, patient advocacy organizations and pharmaceutical industry will deepen our understanding of how to diagnose and treat CIDP. [ABSTRACT FROM AUTHOR]

Objectively as possible using disability and impairment scales. Applying these outcome measures consistently in clinical practice aids in recognizing the effectiveness (or lack thereof) of a treatment and facilitates timely consideration of alternative diagnoses or treatments. This review provides an overview of the current perspectives on the diagnostic process and first-line treatments for managing the disease. [ABSTRACT FROM AUTHOR]

Valid, responsive blood biomarkers specific to peripheral nerve damage would improve management of peripheral nervous system (PNS) diseases. Neurofilament light chain (NfL) is sensitive for detecting axonal pathology but is not specific to PNS damage, as it is expressed throughout the PNS and CNS. Peripherin, another intermediate filament protein, is almost exclusively expressed in peripheral nerve axons. We postulated that peripherin would be a promising blood biomarker of PNS axonal damage. We demonstrated that peripherin is distributed in sciatic nerve, and to a lesser extent spinal cord tissue lysates, but not in brain or extra-neural tissues. In the spinal cord, anti-peripherin antibody bound only to the primary cells of the periphery (anterior horn cells, motor axons and primary afferent sensory axons). In vitro models of antibody-mediated axonal and demyelinating nerve injury showed marked elevation of peripherin levels only in axonal damage and only a minimal rise in demyelination. We developed an immunoassay using single molecule array technology for the detection of serum peripherin as a biomarker for PNS axonal damage. We examined longitudinal serum peripherin and NfL concentrations in individuals with Guillain-Barré syndrome (GBS, n = 45, 179 time points), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP, n = 35, 70 time points), multiple sclerosis (n = 30), dementia (as non-inflammatory CNS controls, n = 30) and healthy individuals (n = 24). Peak peripherin levels were higher in GBS than all other groups (median 18.75 pg/ml versus < 6.98 pg/ml, P < 0.0001). Peak NfL was highest in GBS (median 220.8 pg/ml) and lowest in healthy controls (median 5.6 pg/ml), but NfL did not distinguish between CIDP (17.3 pg/ml), multiple sclerosis (21.5 pg/ml) and dementia (29.9 pg/ml). While peak NfL levels were higher with older age (rho = +0.39, P < 0.0001), peak peripherin levels did not vary with age. In GBS, local regression analysis of serial peripherin in the majority of individuals with three or more time points of data (16/25) displayed a rise-and-fall pattern with the highest value within the first week of initial assessment. Similar analysis of serial NfL concentrations showed a later peak at 16 days. Group analysis of serum peripherin and NfL levels in GBS and CIDP patients were not significantly associated with clinical data, but in some individuals with GBS, peripherin levels appeared to better reflect clinical outcome measure improvement. Serum peripherin is a promising new, dynamic and specific biomarker of acute PNS axonal damage. [ABSTRACT FROM AUTHOR]

It is unclear whether frequently used cutoff values for outcome measures defining minimal clinically important differences (MCIDs) can accurately identify meaningful deterioration in chronic inflammatory demyelinating polyneuropathy (CIDP). We used data from the immunoglobulin overtreatment in CIDP (IOC) trial, in which 60 clinically stable patients with CIDP were randomized to intravenous immunoglobulin (IVIg) withdrawal or continuation. We calculated change scores of the Inflammatory Rasch‐Built Overall Disability Scale (I‐RODS), grip strength, and Medical Research Council‐sum score (MRC‐SS) and classified visits based on a treatment anchor (ie, decision to restart/increase treatment after reaching a predefined early endpoint of deterioration). The variability of scores in patients without deterioration was calculated using the limits of agreement. We defined optimized MCIDs for deterioration and specific combinations of MCIDs from different outcome measures, and subsequently calculated the accuracies of the (combined) MCIDs. Substantial variability was found in scores of the I‐RODS, grip strength and MRC‐SS in patients without deterioration over time, and most MCIDs were within the limits of the variability observed in patients without deterioration. Some MCID cut‐offs were insensitive but highly specific for detecting deterioration, for example, the MCID‐SE of −1.96 of the I‐RODS and −2 point on the MRC‐SS. Others were sensitive, but less specific, for example, −4 centiles of the I‐RODS. Some combined MCIDs resulted in high specificities and moderate sensitivities. Our results suggest that clinically important deterioration cannot be distinguished from variability over time with currently used MCIDs on the individual level. Combinations of MCIDs might improve the accuracy of determining deterioration, but this needs validation. [ABSTRACT FROM AUTHOR]

The objectives were to (a) assess the diagnostic value of testing clinically affected and unaffected limbs with nerve conduction studies (NCS) in patients with the asymmetric chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) variant and to define the most useful strategy for diagnosis, and (b) describe treatment response and long‐term outcome. We performed a retrospective study and included patients with a multifocal distribution of symptoms and signs, who met the probable or definite EFNS/PNS diagnostic categories for CIDP. We included 34 patients and 32 NCS datasets were available. Of these 32 patients, 25 (78%) met the electrodiagnostic criteria for definite or probable CIDP and seven (22%) for possible CIDP. Patients fulfilling the possible electrodiagnostic criteria and a supportive criterion were considered as probable CIDP. NCS of the clinically affected forearm and leg led to a probable or definite diagnosis in 13 patients (41%). Measuring both arms up to Erb's point led to a probable or definite diagnosis in 25 patients (78%), after which NCS of both legs did not contribute to additional probable or definite diagnoses. In total, 30% of patients treated with dexamethasone and 94% of patients treated with intravenous immunoglobulins (IVIg) responded. IVIg withdrawal attempts were successful in 21% of patients. After measuring the clinically affected arm up to Erb's point, NCS of the unaffected arm to Erb's point has the highest additional diagnostic yield in patients with asymmetric CIDP. Patients seem to respond better to IVIg than to corticosteroids and long‐term treatment is often required, although IVIg withdrawal was successful in 21%. [ABSTRACT FROM AUTHOR]

B-cell activating factor (BAFF) is a crucial cytokine for differentiation and survival of B-cells and correlates to disease activity in some auto-immune diseases. To evaluate BAFF as a biomarker for disease activity in chronic inflammatory demyelinating polyneuropathy (CIDP), serum BAFF levels were measured at varying disease stages: patients starting treatment, patients starting treatment withdrawal, patients in remission and healthy controls. Serum BAFF levels were elevated in patients compared to healthy controls, but did not differ between patients starting treatment and patients in remission. Serum BAFF levels did not change with or predict treatment response or relapse. Serum BAFF is not a responsive biomarker reflecting disease activity in CIDP. [ABSTRACT FROM AUTHOR]