Multiple sclerosis with medullary plaques and fatal sleep apnea (Ondine's curse)

Abstract

We report 2 patients with multiple sclerosis (MS) who were symptomatic but ambulatory, and died in their sleep. Sleep studies in 1 patient showed hypercarbia and hypoxia accompanying sleep. In both cases autopsy showed plaques of multiple sclerosis in the medulla oblongata, incompletely involving the neuroanatomic areas of the medullary reticular formation controlling automatic breathing. A systematic analysis of the location of the plaques in relation to areas known to be important in breathing control revealed that the regions corresponding to the ventral nuclear complex of respiratory control in animals were incompletely and unilaterally involved in both cases. Close correlation with nuclei that have been demonstrated in animal experiments to be important in descending respiratory control of phrenic and intercostal musculature was not possible due to possible differences in anatomy between animals and humans, and the fact that plaques of MS affect axons of passage and spare neuronal cell bodies. Nevertheless, the cases clearly illustrate that patchy, unilateral lesions of the medullary reticular formation in humans can give rise to sleep disordered breathing. The cases also illustrate the risk of death during sleep in MS patients with demyelination in the medulla oblongata, and demonstrate the need to carefully examine the medulla in MS patients if they die unexpectedly during sleep.