Citations

ABSTRACTBackground and AimsNerve conduction studies (NCS) are integral to diagnosing chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), but their role in predicting treatment outcomes remains underexplored. This study evaluates NCS changes at first follow‐up (first NCS changes) as predictors of treatment success in CIDP, focusing on their correlation with clinical outcomes over time.MethodsNewly diagnosed CIDP patients meeting the 2021 EAN/PNS criteria were retrospectively evaluated. Baseline and first follow‐up NCS parameters were compared with clinical outcomes, assessed by the Neuropathy Impairment Score (NIS) and Inflammatory Neuropathy Cause and Treatment (INCAT) disability score. All patients received first‐line immunotherapy (intravenous immunoglobulin, corticosteroids, or plasma exchange).ResultsOf 39 treated patients, 26 (66.7%) were responders based on improving NIS trends, while 13 (33.3%) were nonresponders. Responders showed significant improvements at the first follow‐up in fibular compound muscle action potential (CMAP) amplitude, ulnar CMAP amplitude, summated CMAP amplitudes, and fibular motor conduction velocity. Changes in fibular CMAP amplitude consistently correlated with NIS (R = −0.8 to −0.6, p ≤ 0.004) and INCAT disability score improvements (R = −0.6 to −0.3, p ≤ 0.032) across all follow‐up intervals up to 60 months. Ulnar and summated CMAP amplitude changes also correlated with clinical outcomes, though their associations were less sustained than those of fibular CMAP amplitude.InterpretationThe first change in fibular CMAP amplitude is a reliable biomarker for predicting CIDP treatment response, with ulnar and summated CMAP amplitudes as alternatives when the fibular response is absent. Our findings highlight the utility of first NCS changes in monitoring and predicting treatment outcomes in CIDP.

ABSTRACTBackground and AimsChronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is difficult to distinguish from mimicking disorders, with misdiagnosis resulting in IVIG overutilization. We evaluate a clinical‐electrophysiological model to facilitate CIDP versus mimic neuropathy prediction.MethodsUsing the European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) 2021 CIDP guidelines we derived 26 clinical and 144 nerve conduction variables. The model was generated and validated utilizing total CIDP (n = 129) and mimics (n = 309); including (1) IgG4‐nodopathies; (2) POEMS (polyneuropathy–organomegaly–endocrinopathy–monoclonal protein‐skin changes); (3) anti‐myelin‐associated‐glycoprotein; (4) paraneoplastic; (5) Waldenström B‐cell lymphoma; (6) diabetic neuropathies; (7) amyloidosis; (8) Charcot–Marie–Tooth; (9) motor neuropathies/neuronopathies; and (10) idiopathic‐inflammatory‐myopathies.ResultsWe analyzed 9282 clinical and 51 408 electrophysiological data points. Univariate analysis identified 11 of 26 clinical variables with significant odds ratios. A multivariate regression model using four clinical and two electrophysiologic variables achieved 93% area‐under‐curve (95% CI 91–95): progression over 8 weeks (OR 40.66, 95% CI 5.31–311.36), absent autonomic involvement (OR 17.82, 95% CI 2.93–108.24), absent muscle atrophy (OR 16.65, 95% CI 3.27–84.73), proximal weakness (OR 3.63, 95% CI 1.58–8.33), ulnar motor conduction velocity slowing < 35.7 m/s (OR 5.21, 95% CI 2.13–12.76), and ulnar motor conduction block (OR 13.37, 95% CI 2.47–72.40). A web‐based probability calculator (https://news.mayocliniclabs.com/cidp‐calculator/) was developed, with 100% sensitivity and 68% specificity at a 92% probability threshold. Specificity improved to 93% when considering “red flags,” electrophysiologic criteria, and laboratory testing.InterpretationA probability calculator using clinical electrophysiological variables assists CIDP differentiation from mimics, with scores below 92% unlikely to have CIDP. The highest specificity is achieved by considering clinical “red flags,” electrophysiologic demyelination, and laboratory testing.

Abstract Vasculitic neuropathy is caused by inflammatory destruction of nerve blood vessels resulting in nerve ischaemia. Nerve vasculitis can be divided into two categories based on vessel size: large-arteriole vasculitis (≥75 µm) and microvasculitis (&lt;75 µm). Herein, we characterize the clinical features of nerve large-arteriole vasculitis in comparison to nerve microvasculitis. This is a retrospective cohort study of patients evaluated and biopsied at Mayo sites between 2001 and 2020. We collected clinical and histopathological data from patients whose nerve biopsies were either diagnostic or highly suggestive of nerve vasculitis. Two hundred and seventy-eight cases were identified: 125 cases of large-arteriole vasculitis and 153 cases of microvasculitis. Nerve large-arteriole vasculitis presented with a more acute (50.4% versus 26.8%) versus chronic onset (33.6% versus 57.5%) than nerve microvasculitis (P = 0.0001). Nerve microvasculitis had longer mean time to diagnosis (10.5 versus 4.3 months; P &lt; 0.0001) and longer time to plateau (8.9 versus 3.5 months; P &lt; 0.0001). Nerve large-arteriole vasculitis typically presented as distal asymmetric polyneuropathy (48.0%), whereas nerve microvasculitis typically presented as radiculoplexus neuropathy/polyradiculoneuropathy (more proximal involvement of shoulder and thigh) (43.8%) (P &lt; 0.0001). Systemic autoimmune disease was more common in nerve large-arteriole vasculitis (70.4% versus 22.9%, odds ratio, 8.0; 95% confidence interval, 4.7–13.7; P &lt; 0.0001). Nerve microvasculitis was significantly related to non-systemic vasculitis (71% versus 23%, odds ratio, 7.9; 95% confidence interval, 4.6–13.6; P &lt; 0.0001). Nerve microvasculitis had more autonomic involvement (24.2% versus 7.2%, odds ratio, 4.1; 95% confidence interval, 1.9–8.9; P = 0.0002). Nerve large-arteriole vasculitis and nerve microvasculitis have different but overlapping clinical features. Nerve large-arteriole vasculitis usually presents with acute onset, distal asymmetric polyneuropathy, associated with other autoimmune diseases and systemic involvement. In contrast, nerve microvasculitis usually presents with a subacute/chronic onset, as radiculoplexus neuropathy/polyradiculopathy (distal and proximal pattern) with autonomic involvement, and is more often a form of non-systemic vasculitis.

Recent literature has emphasized the role of hand surgeons in screening patients with carpal tunnel syndrome (CTS) for amyloidosis by performing a carpal tunnel synovial biopsy during open carpal tunnel release (CTR). This has led to misconceptions about the diagnostic utility of synovial biopsy and the clinical evaluation of suspected amyloidosis. Controversy over carpal tunnel biopsy is exacerbated by minimally invasive advances in CTR procedures. This current perspective aims to determine the role of carpal tunnel synovial biopsy in amyloidosis and provide an update for hand surgeons regarding the nuances of amyloidosis. We conclude that carpal tunnel synovial biopsy should not be performed without CTS symptoms but only in patients meeting criteria for open CTR such as in those with severe symptoms which have failed nonoperative treatment and minimally invasive procedures are contraindicated. A screening approach for amyloidosis is proposed in patients presenting with CTS symptoms. Despite advances in the understanding, treatment, and diagnosis of amyloidosis, there remains a need for accurate, specific, and sensitive diagnostic tests.

Abstract Background Autoimmunity targeting GQ1b is associated with group of disorders that includes Miller-Fisher Syndrome (MFS), Bickerstaff Brainstem Encephalitis (BBE) and classic Guillain Barre Syndrome (GBS) with ophthalmoplegia. Collectively these are referred to as GQ1B-IgG related syndromes. The prevalence of GQ1b-IgG in this population of patients is high and has been reported to be &gt;80% in well-defined clinical cohorts. Clinical phenotypic presentation is diverse and requires highly accurate antibody testing. The objective of this study was to evaluate a newly developed custom GQ1b-IgG assay, using a semi-quantitative ELISA-based method. Methods A GQ1b-IgG ELISA was developed and validated. Patient sera along with assay controls and a single-point calibrator are diluted and incubated in duplicate wells in a 96-well plate coated with GQ1b antigen. The plate is washed and incubated with anti-human-IgG secondary antibody conjugated with HRP. After a colorimetric reaction, optical densities (OD) are read. The OD of patient samples are compared against the calibrator, generating a cut-off index (COI). Samples ≥1.0 COI are considered positive. During the validation phase, analytical and clinical performance characteristics were evaluated. Studies included assessment of imprecision at multiple concentrations of GQ1b-IgG, accuracy using method comparison, analytical sensitivity and specificity, reference range, common interferences, plate drift, and clinical performance in relevant disease and control cohorts. Results Intra-assay imprecision (coefficient of variation; %CV) ranged from 1.0 - 16% across all concentrations of GQ1b-IgG. Inter-assay imprecision (%CV) ranged from 12.4 - 44.5% but was &lt;20% at or above the assay cut-off. We found perfect qualitative agreement with an independent ELISA reference method (20 positive and 20 negative samples selected based on reference method results [reference interval &lt;1:100]). Limit of detection (LOD) was calculated at a COI of 0.22. To assess analytical specificity, 40 samples with high concentrations of immunoglobulins (hypergammaglobulinemia [N=15], IgG M-protein [N=15] and systemic lupus erythematosus [N=10] were tested and all were negative. A reference interval study was performed on 140 healthy donor serums, all were negative. Interference studies were conducted on 2 positive and 2 negative serum samples, spiked for highly hemolytic (1000 mg/dL), lipemic (2000 mg/dL) and icteric (60 mg/dL) conditions. There was no impact on the assay even with high levels of a given interferent. Plate drift on 2 distinct patient pools tested across the plate (COI range 0.7 - 1.3) had overall plate CV’s ≤10%. ROC analysis was performed on a cohort of 278 patient samples (15 MFS cases and 263 controls [suspected demyelinating neuropathy or disease mimics]). A cut-off value of 1.0 (COI) was selected based on the Youden index. At this cut-off, clinical sensitivity for MFS was 87% while clinical specificity was 99.2%. Conclusions The observed performance of the GQ1b-IgG ELISA was acceptable for clinical laboratory implementation. A COI of ≥ 1.0 was selected for clinical use.

Abstract Introduction/Aims Point‐of‐care ultrasound of the diaphragm is highly sensitive and specific in the detection of neuromuscular diaphragmatic dysfunction. In some patients with neuromuscular diaphragmatic dysfunction, paradoxical thinning of the diaphragm during inspiration is observed on ultrasound; however, its frequency, electrodiagnostic associations, and prognostic significance remain uncertain. Methods Medical records of patients presenting to two electrodiagnostic laboratories (Mayo Clinic, Rochester, Minnesota and University of Alberta, Edmonton, Alberta) from January 1, 2022 to December 31, 2022, for evaluation of suspected neuromuscular respiratory failure, were reviewed. Results 214 patients were referred and 19 patients excluded due to incomplete information. Of 195 patients (384 hemidiaphragms), 104 had phrenic neuropathy, 12 had myopathy, and 79 had no evidence of neuromuscular disease affecting the diaphragm. Paradoxical thinning occurred in 31 (27%) patients with neuromuscular diaphragmatic dysfunction and was unilateral in 30, the majority (83%) having normal contralateral ultrasound. Phrenic nerve conduction studies and diaphragm electromyography results did not distinguish patients with paradoxical thinning versus without. Most patients (71%) with paradoxical thinning required non‐invasive ventilation (NIV), including 16 with unilateral paradoxical thinning. Paradoxical thinning and BMI ≥30 kg/m 2 were risk factors for requiring NIV in multivariable logistic regression analysis, with odds ratios of 2.887 (95% CI:1.166, 7.151) and 2.561 (95% CI: 1.186, 5.532), respectively. Discussion Paradoxical thinning of the diaphragm occurs in patients with prominent neuromuscular diaphragmatic dysfunction, most commonly from phrenic neuropathy, and is a significant risk factor for requiring NIV. Unilateral paradoxical thinning is sufficient for needing NIV. BMI ≥30 kg/m 2 additionally increases risk of requiring NIV in patients with neuromuscular diaphragmatic dysfunction.