Journal of the Peripheral Nervous System最新文献

Background and aims: The Inflammatory Rasch-built Overall Disability Scale (I-RODS) is an effective activity measure for use in inflammatory peripheral neuropathy. The aim of this study was to validate the Korean version of the I-RODS in patients with chronic inflammatory demyelinating polyneuropathy (CIDP), Guillain-Barré syndrome (GBS), anti-myelin-associated glycoprotein (MAG) neuropathy, and autoimmune nodopathy.

Methods: A total of 120 patients underwent clinical evaluations, which included the I-RODS, Inflammatory Neuropathy Cause and Treatment (INCAT) assessment, and Jamar grip strength (kg) measurement. Follow-up assessments were performed for 83 patients during their regular clinic visits. To estimate the test-retest reliability of the I-RODS, the scale was reapplied to a subset of 16 patients within 2-7 days of the initial test. Overall, reliability, validity, and responsiveness of the I-RODS were evaluated.

Results: Internal consistency was good, as indicated by a person separation index of 0.966. The raw and standardized Cronbach's alpha values were both 0.974. The test-retest reliability analyzed using the intraclass correlation coefficient (ICC) was also high (ICC = 0.972). The I-RODS showed a strong correlation with INCAT scores (ρ = -0.81, p < .001) and a moderate correlation with grip strength (ρ = 0.61, p < .001). Furthermore, the sensitivity for detecting clinically meaningful improvement was highest for grip strength (60.4%) followed by I-RODS (52.1%), while for capturing deterioration, it was highest for I-RODS (80.0%).

Interpretation: The Korean version of the I-RODS is a reliable and valid tool for measuring disability in patients with inflammatory neuropathy. The I-RODS is useful for both clinical practice and research applications.

Background and aims: Peripheral nerve injuries often require bridging when direct repair is not feasible. Nerve autografts are the gold standard, but they can lead to donor site morbidity. Silk fibroin-based nerve conduits, like the novel SILKBridge, offer a promising alternative. This pilot study evaluates the mid-term outcomes of the first in-human digital nerve reconstruction using the SILKBridge, focusing on sensory recovery, complication rates, patient-reported outcomes, and biological integration.

Methods: This study included four patients with digital nerve defects reconstructed using the SILKBridge. Clinical assessments included two-point discrimination, Semmes-Weinstein monofilament testing, and pain evaluation using the Numeric Rating Scale. Sonographic assessments were also performed to evaluate the conduit's biointegration and potential complications.

Results: At a mean follow-up of 32 months, all patients demonstrated satisfactory sensory recovery and reported minimal to no pain. Sonographic assessments confirmed effective biointegration with no signs of inflammation or scarring.

Interpretation: The mid-term evaluation of the first in-human digital nerve reconstruction with the SILKBridge revealed safety, efficiency, and favorable biocompatibility properties. Further studies with larger cohorts are needed to validate these findings and compare them with other nerve repair methods.

Background and aims: Ultrasound nerve cross-sectional area (CSA) of patients affected with axonal neuropathy usually shows normal value. Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) seems to represent an exception, showing smaller CSA, but previous reports did not test for biallelic RFC1 gene repeat expansions.

Methods: We compared nerve CSA from CANVAS patients (tested positive for biallelic RFC1 gene repeat expansions) with the CSA from a group of patients with chronic idiopathic axonal polyneuropathy (CIAP) who tested negative for RFC1 gene repeat expansions, hereditary axonal neuropathy (Charcot-Marie-Tooth type 2, CMT2), and Friedreich ataxia (FRDA).

Results: We enrolled 15 CANVAS patients (eight men, mean age 66.3 ± 11.5 years, mean disease duration 9.3 ± 4.1 years), affected with sensory axonal neuronopathy. Controls consisted of 13 CIAP (mean age 68.5 ± 12.8 years, seven men), seven CMT2 (mean age 47.9 ± 18.1 years, four men), 12 FRDA (mean age 33.7 ± 8.8, five men). Nerve ultrasound was performed at median, ulnar, sciatic, sural, and tibial nerves and brachial plexus, bilaterally. The nerve CSA from CANVAS patients was significantly smaller than the one from the other cohorts at several sites with significant and high accuracy at Receiver-operating characteristic (ROC) curve analyses. RFC1 AAGGG pentanucleotide expansion, disease duration, and disability did not correlate with CSA at any site, after Bonferroni correction.

Interpretation: Decreased sonographic nerve sizes, in arms and legs, in patients with sensory neuropathy and normal motor conduction studies could point to CANVAS-spectrum disease and help guide appropriate genetic testing.

Background and aims: Porphyrias are inherited metabolic disorders caused by mutations in genes encoding enzymes involved in the heme biosynthetic pathway, leading to the accumulation of heme precursors. Acute hepatic porphyrias (AHP), including acute intermittent porphyria (AIP), can present with predominant peripheral neurological manifestations, often leading to a misdiagnosis as Guillain-Barré syndrome.

Methods: We report a case of AIP initially presenting as a peripheral neuropathy mimicking Parsonage-Turner syndrome (neuralgic amyotrophy, NA). Clinical and electrophysiological evaluations were conducted, including nerve conduction studies and needle electromyography (EMG).

Results: A 41-year-old woman presented with burning pain and electric shock-like sensations in the shoulders and trunk, alongside asymmetrical motor weakness in the upper limbs affecting arm abduction and finger extension. Electrophysiological evaluation revealed involvement of the superior trunk of the brachial plexus and the posterior interosseous nerve. Initially diagnosed with NA, she showed significant improvement in proximal strength over nine months but relapsed at fourteen months with severe finger extension weakness. Concurrent severe abdominal pain with constipation led to the identification of elevated urinary porphobilinogen (PBG) and delta-aminolevulinic acid (ALA) levels, confirming AHP and specifically AIP via genetic and biochemical testing. The patient received hemin and givosiran infusions, resulting in decreased ALA levels, improvement of motor weakness, and no further attacks.

Interpretation: This case underscores the need to consider AIP in the differential diagnosis of acute neuropathies like NA, especially when accompanied by abdominal pain and severe constipation. Early recognition and appropriate testing for PBG and ALA can prevent misdiagnosis and enable targeted treatment.

Background and aims: Small-fibre neuropathy (SFN) is associated with glucose dysregulation, including impaired glucose tolerance (IGT) and type 2 diabetes (T2D). Corneal confocal microscopy (CCM) offers a non-invasive tool to assess corneal nerve damage and dendritic cell density (DCD). In this study, we investigated corneal DCD in patients with SFN and glucose dysregulation, defined as IGT or T2D.

Methods: We enrolled 38 patients with SFN + glucose dysregulation, 51 with SFN + non-glucose dysregulation and 20 healthy controls. All participants underwent neurological examination, neurophysiology and CCM.

Results: Individuals with SFN and glucose dysregulation had higher DCD compared with healthy controls (p = .01), and mature DCD was higher in IGT SFN patients than in T2D patients.

Interpretation: Higher DCD in IGT compared with controls and patients with established T2D may suggest that DCD is a biomarker of early neuropathy.

Background and aims: Colony-stimulating factor 1 (CSF1) is a growth factor secreted by dorsal root ganglia (DRG) neurons important for DRG macrophages and spinal cord (SC) microglia injury-induced proliferation and activation, specifically released after spared nerve injury (SNI). In this study, we investigated if SNI-induced CSF1 expression and perineuronal rings of macrophages around mouse DRG neurons vary between L3-L5 DRG and with the neuronal type, and if the CSF1⁺ neuronal projections at the SC dorsal horns were associated with an increased microglial number in the corresponding laminae.

Methods: Seven days after surgery, L3-L5 DRG as well as their corresponding segments at the SC level were collected, frozen, and cut. DRG sections were double-immunostained using antibodies against CSF1 and NF200, CGRP or IB4, while SC sections were immunostained using a fluorescent Nissl Stain and analyzed for CX3CR1-GFP microglia number and distribution by an in-house ImageJ Plug-in.

Results: Our results showed that SNI-induced CSF1 expression was common for all subtypes of mouse DRG neurons, being responsible for attracting more resident macrophages around them in a DRG-dependent manner, with L4 showing the stronger response and CSF1⁺/NF200⁺ neurons showing the highest incidence. Even though the total number of microglia in the SC ipsilateral dorsal horns increased after SNI, the increase at their specific laminar projection sites did not mirror the incidence of DRG neuronal subtypes among CSF1⁺ neurons.

Interpretation: Taken together, these results contribute to a more comprehensive understanding of the connection between CSF1 and macrophage/microglia response after SNI and emphasize the importance of considering L3-L5 DRG individually when investigating SNI-neuropathic pain pathogenesis in mice.

Background and aims: The Charcot-Marie-Tooth Disease Health Index (CMT-HI) is a disease-specific, patient-reported disease burden measure. As part of an international clinical trial readiness study, individuals with CMT1A (ages 18-75 years) underwent clinical outcome assessments (COAs), including the CMT-HI, to capture their longitudinal perspective on the disease burden.

Methods: Two hundred and fifteen participants underwent serial COAs including the CMT-HI, CMT Functional Outcome Measure (CMT-FOM), CMT Neuropathy Score (CMTNSv2R), and CMT Exam Score (CMTES/CMTES-R). Correlations between the total and subscale scores for the CMT-HI and other COAs were determined. Changes in the CMT-HI scores over 12 months were assessed using paired t-tests. The minimum clinically important difference (MCID) for the CMT-HI and its subscales were calculated by anchoring to a participant global impression of change scale.

Results: At baseline, CMT1A participants were 44.5 ± 15 years old (range: 18-75) and 58% were women. The mean CMT-HI was 25.7 ± 18.8 (range: 0-91.9; 100 reflecting maximal disease burden). The CMT-HI correlated with the CMT-FOM (r = .54, p < .0001), CMTNSv2R (r = .48, p < .0001), and CMTES/CMTES-R (r = .52/r = .54, p < .0001). Disease burden was greater in women than in men (CMT-HI 29.1 ± 19.1 vs. 21.2 ± 17.3, p = .001). Over 12 months, there was a nonsignificant mean increase in CMT-HI of 0.40 ± 10.0 (n = 189, p = .89). The MCID for the CMT-HI total score was 3.8 points (95% CI: 1.7-5.9).

Discussion: Patient-reported disease burden in CMT1A as measured by the CMT-HI is associated with measures of neurologic impairment and physical functioning. Women reported a higher disease burden than men. These data will inform the design of clinical trials in CMT1A.

Background and aims: The aim of this study is to validate and perform a region-specific adjustment of the Erasmus GBS Respiratory Insufficiency Score (EGRIS) and identify potential predictors of prolonged mechanical ventilation (PMV) among Guillain-Barré syndrome (GBS) patients from Bangladesh.

Methods: We enrolled GBS patients from four prospective observational cohort studies conducted in Bangladesh. Accuracy of EGRIS to predict the requirement of MV in <7 days of study entry was evaluated. Model performance was assessed by discrimination (ability of the model to differentiate between patients who needed MV or not) and calibration (accuracy of absolute risk estimates). PMV was defined as duration of MV >14 days. Potential predictors for PMV were evaluated by Cox regression.

Results: A total of 594 GBS patients aged ≥6 years old were enrolled; of whom 541 patients had complete EGRIS data prior to MV and were included in validation analysis. EGRIS correctly distinguished between patients requiring MV or not in 81% pairs (AUC = 0.81). EGRIS overestimated the probability of MV than the observed probability (41% vs. 20%) which was resolved by updating of the model intercept. Inability to flex hip at day 7 of start of MV was the strongest predictor for PMV with predicted probabilities of 82%.

Interpretation: EGRIS accurately predicts the need for MV in GBS patients from Bangladesh. This study developed a region-specific version of EGRIS and identified predictors of PMV. These findings can assist clinicians to identify patients at high risk of developing respiratory failure and requiring PMV to ensure timely intubation and tracheostomy of the patients in low resource settings.