Brainstem respiratory control: substrates of respiratory failure of multiple system atrophy

Multiple system atrophy may manifest with severe respiratory disorders, including sleep apnea and laryngeal stridor, which reflect a failure of automatic control of respiration. This function depends on a pontomedullary network of interconnected neurons located in the parabrachial/Kölliker Fuse nucleus in the pons, nucleus of the solitary tract, and ventrolateral medulla. Neurons in the preBötzinger complex expressing neurokinin-1 receptors are critically involved in respiratory rhythmogenesis, whereas serotonergic neurons in the medullary raphe and glutamatergic neurons located close to the ventral medullary surface are involved in central chemosensitivity to hypercapnia, hypoxia, or both. Pathological studies using selective neurochemical markers indicate that these neuronal groups are affected in multiple system atrophy. This finding may provide potential anatomical substrates for the respiratory manifestations of the disease.