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ALS is mostly diagnosed based on clinical signs, using the revised El Escorial criteria, which require signs of both upper motor neuron (e.g., spasticity, brisk reflexes) and lower motor neuron damage (e.g., muscle wasting, twitching) in multiple body regions (Brotman et al., 2025)

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J Pharmacol Exp Ther 311:99108 Clancy RM, Levartovsky D, Leszczynska-Piziak J, Yegudin J, Abramson SB (1994) Nitric oxide reacts with intracellular glutathione and activates the hexose monophosphate shunt in human neutrophils: evidence for S-nitrosoglutathione as a bioactive intermediary