Primary lateral sclerosis: application and validation of the 2020 consensus diagnostic criteria in an expert opinion-based PLS cohort.

BACKGROUND: Validation of the 2020 consensus criteria for primary lateral sclerosis (PLS) is essential for their use in clinical practice and future trials. METHODS: In a large cohort of patients diagnosed with PLS by expert opinion prior to the new criteria with detailed clinical baseline evaluation (n=107) and longitudinal follow-up (n=63), we applied the new diagnostic criteria and analysed the clinical phenotype, electromyography (EMG), diagnostic accuracy and prognosis, adding neurofilaments and MRI as potential biomarkers. RESULTS: The criteria for definite PLS were met by 28% and those for probable PLS by 19%, whereas 53% did not meet the full criteria at baseline, mainly due to the time, EMG and region criteria. Patients not meeting the criteria had less generalised upper motor neuron involvement but were otherwise similar in demographic and clinical characteristics. All patients with definite and probable PLS maintained PLS diagnosis during follow-up, while four patients not meeting the criteria developed clinical lower motor neuron involvement. Definite PLS cases showed improved survival compared with probable PLS and patients who did not meet the criteria. Despite a clinical PLS phenotype, fibrillation potentials/positive sharp waves and fasciculations in one or more muscles were a frequent EMG finding, with the extent and prognostic significance depending on disease duration. Serum neurofilament light and a multiparametric MRI fibre integrity Z-score correlated with clinical parameters and were identified as potential biomarkers. CONCLUSION: Validation of the 2020 PLS consensus criteria revealed high diagnostic certainty and prognostic significance, supporting their value for research and clinical practice.

US-based Real-time Elastography for the Detection of Fibrotic Gut Tissue in Patients with Stricturing Crohn Disease.

PURPOSE: To assess whether ultrasonography (US)-based real-time elastography (RTE) can be used to detect gut fibrosis. MATERIALS AND METHODS: In this institutional review board-approved, prospective, proof-of-concept study, unaffected and affected gut segments in 10 patients with Crohn disease (four women, six men; median age, 49 years) were examined pre-, intra-, and postoperatively with US, including RTE to assess strain. Disease activity was scored by using the Limberg index on the basis of (a) bowel wall thickness and (b) size and extent of Doppler signal. After surgical resection, strain of full gut wall segments was measured with direct tensiometry. Gut wall layers, fibrosis, and collagen content were quantified histologically. Aggregated data per patient, disease status, and available measurements were assessed with mixed-effects models. RESULTS: Unaffected versus affected gut segments yielded higher RTE (mean ± standard deviation, 169.0 ± 27.9 vs 43.0 ± 25.9, respectively) and tensiometry (mean, 77.1 ± 21.4 vs 13.3 ± 11.2, respectively) values used to assess strain (both P < .001). There was good correlation between pre-, intra-, and postoperative RTE values of unaffected (intraclass correlation coefficient, 0.572) and affected (intraclass correlation coefficient, 0.830) segments. RTE was not associated with pre- or intraoperative Limberg scores (median, 1 vs 2; P = .255 and .382, respectively). Affected internal (median, 2011 vs 1363 µm; P = .011) and external (median, 929 vs 632 µm; P = .013) muscularis propria, serosa (median, 245 vs 64 µm; P = .019), and muscularis mucosae (median, 451 vs 80 µm; P = .031) were wider than unaffected segments. Width differences of internal muscularis propria and mucularis mucosae were associated with RTE-assessed strain (P = .044 and .012, respectively) and tensiometry-assessed strain (P = .006 and .014, respectively). Masson trichrome (median, 4 vs 0; P < .001) and elastica-van Gieson (median, 805 346 µm(2) vs 410 649 µm(2); P < .001) stains and western blotting (median, 2.01 vs 0.87; P = .009) demonstrated a higher collagen content in affected versus unaffected segments and were associated with RTE-assessed strain (both P < .001) and tensiometry-assessed strain (P < .001 and 0.025, respectively). CONCLUSION: RTE can be used to detect fibrosis in human Crohn disease. Online supplemental material is available for this article.

A biochemical marker panel in MRI-proven hyperacute ischemic stroke-a prospective study.

BACKGROUND: Computer tomography (CT) is still the fastest and most robust technique to rule out ICH in acute stroke. However CT-sensitivity for detection of ischemic stroke in the hyperacute phase is still relatively low. Moreover the validity of pure clinical judgment is diminished by several stroke imitating diseases (mimics). The "Triage® Stroke Panel", a biochemical multimarker assay, detects Brain Natriuretic Peptide (BNP), D-Dimers (DD), Matrix-Metalloproteinase-9 (MMP-9), and S100B protein and promptly generates a Multimarkerindex of these values (MMX). This index has been licensed for diagnostic purposes as it might increase the validity of the clinical diagnosis to differentiate between stroke imitating diseases and true ischemic strokes. Our aim was to prove whether the panel is a reliable indicating device for the diagnosis of ischemic stroke in a time window of 6 h to fasten the pre- and intrahospital pathway to fibrinolysis. METHODS: We investigated all consecutive patients admitted to our stroke unit during a time period of 5 months. Only patients with clinical investigation, blood sample collection and MRI within six hours from symptom onset were included. Values of biochemical markers were analyzed according to the results of diffusion weighted MR-imaging. In addition MMX-values in ischemic strokes were correlated with the TOAST-criteria. For statistical analysis the SAS Analyst software was used. Correlation coefficients were analyzed and comparison tests for two or more groups were performed. Statistical significance was assumed in case of p < 0.05. Finally a ROC-analysis was performed for the MMX-Index. RESULTS: In total 174 patients were included into this study (n = 100 strokes, n = 49 mimics, n = 25 transitoric ischemic attacks). In patients with ischemic strokes the mean NIHSS was 7.6 ± 6.2, while the mean DWI-lesion volume was 20.6 ml (range 186.9 to 4.2 ml). According to the MMX or the individual markers there was no statistically significant difference between the group of ischemic strokes and the group of mimics. Moreover the correlation of the index and the DWI-lesion-volume was poor (p = 0.2). CONCLUSIONS: In our setting of acute MRI-proven ischemic stroke the used multimarker-assay (Triage® Stroke Panel) was not of diagnostic validity. We do not recommend to perform this assay as this might lead to a unjustified time delay.