Ultrasonic detection of vagus, accessory, and phrenic nerve atrophy in amyotrophic lateral sclerosis: Relation to impairment and mortality.

BACKGROUND AND PURPOSE: In amyotrophic lateral sclerosis (ALS), phrenic nerve (PN) atrophy has been found, whereas there is controversy regarding vagus nerve (VN) atrophy. Here, we aimed to find out whether PN atrophy is related to respiratory function and 12-month survival. Moreover, we investigated the relevance of VN and spinal accessory nerve (AN) atrophy in ALS. METHODS: This prospective observational monocentric study included 80 adult participants (40 ALS patients, 40 age- and sex-matched controls). The cross-sectional area (CSA) of bilateral cervical VN, AN, and PN was measured on high-resolution ultrasonography. Clinical assessments included the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R), the Non-Motor Symptoms Questionnaire, and handheld spirometry of forced vital capacity (FVC). One-year survival was documented. RESULTS: The CSA of each nerve, VN, AN, and PN, was smaller in ALS patients compared to controls. VN atrophy was unrelated to nonmotor symptom scores. PN CSA correlated with the respiratory subscore of the ALSFRS-R (Spearman test, r = 0.59, p < 0.001), the supine FVC (r = 0.71, p < 0.001), and the relative change of sitting-supine FVC (r = -0.64, p = 0.001). Respiratory impairment was predicted by bilateral mean PN CSA (p = 0.046, optimum cutoff value of ≤0.37 mm2 , sensitivity = 92%, specificity = 56%) and by the sum of PN and AN CSA (p = 0.036). The combination of ALSFRS-R score with PN and AN CSA measures predicted 1-year survival with similar accuracy as the combination of ALSFRS-R score and FVC. CONCLUSIONS: Ultrasonography detects degeneration of cranial nerve motor fibers. PN and AN calibers are tightly related to respiratory function and 1-year survival in ALS.

Protein Biomarkers in Blood Reflect the Interrelationships Between Stroke Outcome, Inflammation, Coagulation, Adhesion, Senescence and Cancer.

The most important predictors for outcomes after ischemic stroke, that is, for health deterioration and death, are chronological age and stroke severity; gender, genetics and lifestyle/environmental factors also play a role. Of all these, only the latter can be influenced after the event. Recurrent stroke may be prevented by antiaggregant/anticoagulant therapy, angioplasty of high-grade stenoses, and treatment of cardiovascular risk factors. Blood cell composition and protein biomarkers such as C-reactive protein or interleukins in serum are frequently considered as biomarkers of outcome. Here we aim to provide an up-to-date protein biomarker signature that allows a maximum of mechanistic understanding, to predict health deterioration following stroke. We thus surveyed protein biomarkers that were reported to be predictive for outcome after ischemic stroke, specifically considering biomarkers that predict long-term outcome (≥ 3 months) and that are measured over the first days following the event. We classified the protein biomarkers as immune­inflammatory, coagulation-related, and adhesion-related biomarkers. Some of these biomarkers are closely related to cellular senescence and, in particular, to the inflammatory processes that can be triggered by senescent cells. Moreover, the processes that underlie inflammation, hypercoagulation and cellular senescence connect stroke to cancer, and biomarkers of cancer-associated thromboembolism, as well as of sarcopenia, overlap strongly with the biomarkers discussed here. Finally, we demonstrate that most of the outcome-predicting protein biomarkers form a close-meshed functional interaction network, suggesting that the outcome after stroke is partially determined by an interplay of molecular processes relating to inflammation, coagulation, cell adhesion and cellular senescence.